PT J
AU Gao, X
Honn, VK
AF Gao, Xiang
Honn, V Kenneth
TI Recessive oncogenes: current status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE oncogenes; cell cycle; heterozygosity; mutation
ID oncogenes; cell cycle; heterozygosity; mutation
AB Cell growth is under the control of a variety of positive and negative signals. An imbalance of such signals results in deregulation of cell behavior. Recessive oncogenes or tumor suppressor genes, opposite to dominant oncogenes, encode important cellular proteins which could function as negative regulators of the cell cycle, i.e., cell cycle brakes. Inactivation of recessive oncogenes, by allelic deletion, loss of expression, mutation, or functional inactivation by interacting with oncogene products of DNA tumor viruses or with amplified cellular binding proteins, will lead to uncontrolled cell growth or tumor formation. Besides the classic suppressor genes such as the p53 and RB, a growing number of novel tumor suppressor genes have been identified in recent years. While some tumor suppressor genes have been found to be important for the development of a large number of human malignancies (e.g., the p53 gene), others are more tumor type-specific (e.g., the NF-1 gene). Many human cancer types showed abnormalities of multiple tumor suppressor genes, offering strong support to the concept that tumorigenesis and progression result from an accumulation of multiple genetic alterations. In this review, we will begin with an overview (gene, transcript, protein and mechanisms of action) of the tumor suppressor genes (the RB, p53, DCC, APC, MCC, WT1, VHL, MST1, and BRCA1 genes) identified to date and then discuss the specific involvement of tumor suppressor genes in human malignancies including prostate cancer. Various chromosomal regions which potentially may contain tumor suppressor genes also will be reviewed.
C1 [Gao, Xiang] Wayne State University, Department of Radiation Oncology, 432 Chemistry Building, MI48202 Detroit, USA.
[Honn, V Kenneth] Wayne State University, Department of Radiation Oncology, 432 Chemistry Building, MI48202 Detroit, USA.
RP Honn, VK (reprint author), Wayne State University, Department of Radiation Oncology, MI48202 Detroit, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 7
EP 22
PG 16
ER
PT J
AU Nagy, P
AF Nagy, Peter
TI The Facultative Stem Cell: A New Star in Liver Pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE liver; stem cell; oval cell carcinogenesis
ID liver; stem cell; oval cell carcinogenesis
AB Although the unlimited capacity of hepatocytes to divide has been recently proven, more and more evidences support the existence of a primitive stem cell compartment in the liver. These cells probably do not participate in the usual maintenance of the liver mass, but they are activated in case of extensive hepatocyte injury. In vivo the oval cells show deep similarity to the primitive cells of the embryonic liver and seem to be the amplification compartment of the hepatic stem cells. A primitive epithelial cell population can be isolated from the normal liver and maintained in vitro. Studies of these two experimental systems provide most of the data about liver stem cells, which may become important for the clinical practice if we understand how their growth is regulated.
C1 [Nagy, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
RP Nagy, P (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 23
EP 26
PG 4
ER
PT J
AU Denton, G
Price, RM
AF Denton, Graeme
Price, R Michael
TI Immune Responses to the MUC1 Mucin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE MUC1 mucin; immunogenicity; peptide epitopes
ID MUC1 mucin; immunogenicity; peptide epitopes
AB MUC1 mucins are highly glycosylated glycoproteins expressed on the luminal surfaces of glandular epithelia. In breast and ovarian carcinomas, their expression is frequently upregulated and they may be secreted into the circulation of cancer patients. Early studies aimed at the production of anti-MUC1 monoclonal antibodies revealed that MUC1 was a potent immunogen in mice with many monoclonal antibodies raised defining epitopes within the protein core of MUC1. The immunogenicity of MUC1 has now been extended to human studies and it is apparent that patients with breast and ovarian malignant disease are able to mount immune responses against MUC1. These findings provide information on the mechanisms involved in the recognition of MUC1 expressing tumours. The utilisation of MUC1 related immunogens to stimulate immune responses to tumours could lead to the improved management of patients and the development of new immunotherapeutic strategies aimed at the eradication of MUC1 mucin expressing cancers.
C1 [Denton, Graeme] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research Laboratories, NG7 2RD Nottingham, UK.
[Price, R Michael] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research Laboratories, NG7 2RD Nottingham, UK.
RP Denton, G (reprint author), University of Nottingham, School of Pharmaceutical Sciences, Cancer Research Laboratories, NG7 2RD Nottingham, UK.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 27
EP 31
PG 5
ER
PT J
AU Wang, YM
Fodstad, O
Wolf-Dieter, L
Bengtsson, M
Totterman, Th
Funderud, S
Martin, H
Kvalheim, G
AF Wang, Y Meng
Fodstad, Oystein
Wolf-Dieter, Ludwig
Bengtsson, Mats
Totterman, Thomas
Funderud, Steinar
Martin, Hans
Kvalheim, Gunnar
TI An Effective, Direct Immunomagnetic Procedure for Purging Acute Lymphoblastic Leukemia Cells from Human Bone Marrow
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bone marrow; leukemia; transplantation; purging
ID bone marrow; leukemia; transplantation; purging
AB The AB4 monoclonal antibody, which recognizes an HLA-DR epitope, was found to bind to a high percentage of malignant blast cells in samples obtained from 27 patients with ALL. These included 11 of 11 cases with c-ALL, 3 of 7 with pre-pre-B, and 8 of 9 cases with pre-B ALL. AB4 was used together with anti CD10 and anti CD19 antibodies and super-paramagnetic particles for developing a direct immunomagnetic procedure for purging human bone marrow of leukemic cells. In model experiments with KM3 cells admixed to mononuclear bone marrow cells, the individual antibodies each removed 2.8-3.1 logs and 3.6-4.1 logs of tumor cells with one and two purging cycles, respectively. In comparison, the efficacy of a mixture of the three antibodies was 4.4 logs with one treatment cycle, and > 5 logs with repeated treatments. Whereas the use of a commercially available anti-HLA-DR antibody resulted in a 90% reduction in the survival of CFU-GMs and normal blast colonies, AB4 had only a moderate effect on the progenitor cells (46% and 30% reduction). In conjunction with autologous transplantation, bone marrow from a patient was purged with the antibody mixture and 50% of the CFU-GMs and 47% of the CD34+ cells remained after treatment. The patient showed a normal engraftment, reaching a level of 0.5 x 109/l neutrophils by day 20 and 20 x 109/l platelets by day 30. It is concluded that the antibody cocktail may safely and effectively be used for rapid autograft purging in patients with c-ALL, and also in phenotypically selected cases with other subtypes of ALL.
C1 [Wang, Y Meng] The Norwegian Radium Hospital, Department of Tumor Biology, N-0310 Oslo, Montebello, Norway.
[Fodstad, Oystein] The Norwegian Radium Hospital, Department of Tumor Biology, N-0310 Oslo, Montebello, Norway.
[Wolf-Dieter, Ludwig] Freie Universitat, Immunologisches ZellmarkerlaborBerlin, Germany.
[Bengtsson, Mats] University Hospital, Department of ImmunologyUppsala, Sweden.
[Totterman, Thomas] University Hospital, Department of ImmunologyUppsala, Sweden.
[Funderud, Steinar] Norwegian Radium Hospital, Department of ImmunologyOslo, Montebello, Norway.
[Martin, Hans] University Hospital of FrankfurtFrankfurt, Germany.
[Kvalheim, Gunnar] The Norwegian Radium Hospital, Department of Medical Oncology and RadiotherapyOslo, Montebello, Norway.
RP Wang, YM (reprint author), The Norwegian Radium Hospital, Department of Tumor Biology, N-0310 Oslo, Norway.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 32
EP 37
PG 6
ER
PT J
AU Szende, B
Tyihak, E
Szokan, Gy
Katay, Gy
AF Szende, Bela
Tyihak, Erno
Szokan, Gyula
Katay, Gyorgy
TI Possible Role of Formaldehyde in the Apoptotic and Mitotic Effect of 1-Methyl-Ascorbigen
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE formaldehyde; apoptosis; methylascorbigen
ID formaldehyde; apoptosis; methylascorbigen
AB PC-3 human prostate carcinoma cells were treated with 100 mg/ml 1-methyl-ascorbigen (Me-Asc). This treatment resulted in a significant decrease in tumor cell number in parallel with an increase in apoptotic cells. The formaldehyde (HCHO) level in the culture medium was also increased. Dimedone (Di), a known capture molecule forming formal-demethone with HCHO, applied simultaneously with Me-Asc in 10 mg/ml doses diminished the apoptosis-inducing effect of Me-Asc. The possible role of in situ generated HCHO in the induction of apoptosis is discussed.
C1 [Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
[Tyihak, Erno] Hungarian Academy of Sciences, Plant Protection InstituteBudapest, Hungary.
[Szokan, Gyula] Eotvos Lorand University, Faculty of Science, Institute of Chemistry, Department of Organic ChemistryBudapest, Hungary.
[Katay, Gyorgy] Eotvos Lorand University, Faculty of Science, Institute of Chemistry, Department of Organic ChemistryBudapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 38
EP 42
PG 5
ER
PT J
AU Sameni, M
Elliott, E
Ziegler, G
Fortgens, HP
Dennison, C
Sloane, FB
AF Sameni, Mansoureh
Elliott, Edith
Ziegler, Grace
Fortgens, H Philip
Dennison, Clive
Sloane, F Bonnie
TI Cathepsin B and D are Localized at the Surface of Human Breast Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE aspartic proteases; breast cancer; cathepsins; cysteine proteases; oncogenic ras
ID aspartic proteases; breast cancer; cathepsins; cysteine proteases; oncogenic ras
AB Alterations in trafficking of cathepsins B and D have been reported in human and animal tumors. In MCF10 human breast epithelial cells, altered trafficking of cathepsin B occurs during their progression from a preneoplastic to neoplastic state. We now show that this is also the case for altered trafficking of cathepsin D. Nevertheless, the two cathepsins are not necessarily trafficked to the same vesicles. Perinuclear vesicles of immortal MCF10A cells label for both cathepsins B and D, yet the peripheral vesicles found in ras-transfected MCF10AneoT cells label for cathepsin B, cathepsin D or both enzymes. Studies at the electron microscopic level confirm these findings and show in addition surface labeling for both enzymes in the transfected cells. By immunofluorescence staining, cathepsin B can be localized on the outer surface of the cells. Similar patterns of peripheral intracellular and surface staining for cathepsin B are seen in the human breast carcinoma lines MCF7 and BT20. We suggest that the altered trafficking of cathepsins B and D may be of functional significance in malignant progression of human breast epithelial cells. Translocation of vesicles containing cathepsins B and D toward the cell periphery occurs in human breast epithelial cells that are at the point of transition between the pre-neoplastic and neoplastic state and remains part of the malignant phenotype of breast carcinoma cells.
C1 [Sameni, Mansoureh] Wayne State University, Department of Pharmacology, 540 E Canfield, 48201 Detroit, Michigan, USA.
[Elliott, Edith] University of Natal, Department of BiochemistryPietermaritzburg, South Africa.
[Ziegler, Grace] Wayne State University, Department of Pharmacology, 540 E Canfield, 48201 Detroit, Michigan, USA.
[Fortgens, H Philip] University of Natal, Department of BiochemistryPietermaritzburg, South Africa.
[Dennison, Clive] University of Natal, Department of BiochemistryPietermaritzburg, South Africa.
[Sloane, F Bonnie] Wayne State University, Department of Pharmacology, 540 E Canfield, 48201 Detroit, Michigan, USA.
RP Sloane, FB (reprint author), Wayne State University, Department of Pharmacology, 48201 Detroit, USA.
EM bsloane@med.wayne.edu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 43
EP 53
PG 11
ER
PT J
AU Schmidt, B
Valay, M
Nahajevszky, S
Pitlik, E
Fust, Gy
AF Schmidt, Bela
Valay, Marta
Nahajevszky, Sarolta
Pitlik, Ervin
Fust, Gyorgy
TI Complement Synthesis Influencing Factors Produced by Acute Myeloid Leukemia Blast Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AML; complement factor B; C1-INH; C3; C4; IL-1b; IL-2; IL-6; TNF
ID AML; complement factor B; C1-INH; C3; C4; IL-1b; IL-2; IL-6; TNF
AB In a previous study, we found hypercomplementaemia in the sera of acute myeloid leukemia patients. In this study we show that the supernatants of mononuclear cells, derived from peripheral blood taken in the blastic phase, from patients with acute myeloid leukemia (CM-AML) increased the in vitro complement protein synthesis of HepG2 hepatocellular carcinoma cells. This effect of CM-AML was mediated by heat labile soluble factors and involved the synthesis of mRNA and protein. Inhibition experiments with anti-cytokine antibodies and immunoaffinity chromatography revealed that this effect of CM-AML is mostly mediated by IL-1 and IL-6.
C1 [Schmidt, Bela] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi ut 24., H-1502 Budapest, Hungary.
[Valay, Marta] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi ut 24., H-1502 Budapest, Hungary.
[Nahajevszky, Sarolta] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi ut 24., H-1502 Budapest, Hungary.
[Pitlik, Ervin] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi ut 24., H-1502 Budapest, Hungary.
[Fust, Gyorgy] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi ut 24., H-1502 Budapest, Hungary.
RP Fust, Gy (reprint author), National Institute of Haematology, Blood Transfusion and Immunology, H-1502 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 54
EP 59
PG 6
ER
PT J
AU Divald, A
Gyorgydeak, Z
Timar, F
Zalatnai, A
Bognar, R
Horvath, G
Lapis, K
Jeney, A
AF Divald, Andras
Gyorgydeak, Zoltan
Timar, Ferenc
Zalatnai, Attila
Bognar, Rezso
Horvath, Gabor
Lapis, Karoly
Jeney, Andras
TI Modification of Acute and Chronic Liver Damage by Thiazolidine Compounds
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE thiazolidine; liver damage; cirrhosis; hepatoprotection
ID thiazolidine; liver damage; cirrhosis; hepatoprotection
AB As high sulfhydril levels were shown to reduce the action of agents causing tissueinjury, increasing glutathion concentrations may have cytoprotective potential. In this study the hepatoprotective effects of several derivatives of 4carboxy5,5dimethyl thiazolidine, a modulator of glutathion metabolism were studied in rat liver damaged with CCl4. It was found that 4(S) carboxy 5,5dimethyl2 (5'nitro2furyl) thiazolidine (dimethylthiazolidinenitrofuran: DTNF) had the most significant hepatoprotective action; therefore it was subjected to detailed investigation in various models for acute and chronic liver injury. This compound was shown to ameliorate allylalcohol induced liver injury in rats, galactosamine induced hepatitis of mice and CCl4 induced chronic liver damage in rats. Our study on protein synthesis in primary hepatocyte suspension culture showed that cell injury induced by CCl4 could be reduced in the presence of this thiazolidine compound.
C1 [Divald, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Gyorgydeak, Zoltan] Kossuth Lajos University, Institute of Organic ChemistryDebrecen, Hungary.
[Timar, Ferenc] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Bognar, Rezso] Kossuth Lajos University, Institute of Organic ChemistryDebrecen, Hungary.
[Horvath, Gabor] Kossuth Lajos University, Institute of Organic ChemistryDebrecen, Hungary.
[Lapis, Karoly] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Jeney, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 60
EP 63
PG 4
ER
PT J
AU Aszalos, A
AF Aszalos, Adorjan
TI Modulation of Multidrug Resistance in Cancer by Immunosuppresive Agents (Preclinical Studies)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multidrug; resistance; cancer; immunosuppression
ID multidrug; resistance; cancer; immunosuppression
AB This is a brief summary of the status of known immunosuppressive drugs describing their potential and mode of action to reverse the function of the MDR1 gene product, the P glycoprotein. Different aspects of these immunosuppressors have been reviewed in the recent literature. This summary will focus only on those studies which relate to the effect of these drugs on the P-glycoprotein. In addition, studies which may explain the mode of action, but do not deal directly with P-glycoprotein, are also summarized.
C1 [Aszalos, Adorjan] Food and Dung Administration, Department of Health, Education and Welfare, 200 C Street SW, 20204 Washington, USA.
RP Aszalos, A (reprint author), Food and Dung Administration, Department of Health, Education and Welfare, 20204 Washington, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 64
EP 70
PG 7
ER
PT J
AU Sapi, Z
Szapanidisz, J
Toth, B
Bodrogi, I
AF Sapi, Zoltan
Szapanidisz, Jorgosz
Toth, Bernadette
Bodrogi, Istvan
TI DNA Ploidy Pattern in Pure Seminomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA ploidy; image cytometry; seminoma
ID DNA ploidy; image cytometry; seminoma
AB Nuclear extract and image cytometry was used to determine the DNA ploidy pattern of 31 pure seminomas. At least 5-year but usually 10-year follow-up was available to compare the clinical outcome to the DNA ploidy pattern. In 24 cases (77.4%) the DNA indexes (DI) showed tetraploid (1,8 < DI < 2,2) pattern confirming the recent cytogenetic and flow cytometric DNA studies of others. However, in 7 cases (22,6%) the tumors were aneuploid. Out of these aneuploid cases 2 had two subpopulations and 2 had less than 1,8 DI. These latter cases (providing the loss of chromosomal DNA) had elevated AFP levels in serum that raises the question of nonseminomatous transformation without any morphological evidence. Usually, the aneuploid cases had worse prognoses but there was no significant difference. Because of the small number of aneuploid cases wider clinicopathologic studies are required to confirm our results.
C1 [Sapi, Zoltan] St John's Hospital, Department of Pathology, Diosarok u. 1., H-1122 Budapest, Hungary.
[Szapanidisz, Jorgosz] St. John's Hospital, Department of UrologyBudapest, Hungary.
[Toth, Bernadette] St John's Hospital, Department of Pathology, Diosarok u. 1., H-1122 Budapest, Hungary.
[Bodrogi, Istvan] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
RP Sapi, Z (reprint author), St John's Hospital, Department of Pathology, H-1122 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 71
EP 74
PG 4
ER
PT J
AU Orosz, Zs
Besznyak, I
AF Orosz, Zsolt
Besznyak, Istvan
TI Diffuse Inflammatory Pseudotumor of the Testis, the Epididymis and the Spermatic Cord
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE inflammatory pseudotumor; plasma cell granuloma; testis; myofibroblast
ID inflammatory pseudotumor; plasma cell granuloma; testis; myofibroblast
AB Inflammatory pseudotumors have been recognized in many parts of the body. A case of a diffuse variant which involved the testis, the epididymis and the spermatic cord is described. The patient had enlarged left testis for several months. Clinically, the lesion mimicred cancer. Histologically, the lesion contained hyalinized fibrous tissue with spindle cells, plasma cells and lymphocytes. Gradual involvement of vascular channels by the cellular elements of inflammatory pseudotumor was observed. Results of immunohistochemical studies showed a myofibroblast differentiation in the majority of spindle cells: intense antibody staining for smooth muscle actin, muscle specific actin, and vimentin. The ultrastructural findings, intracytoplasmic filaments with dense bodies, were also consistent with the myofibroblastic nature of these cells. The histiocyte differentiation of spindle cells is questionable in our case, because only scattered histiocyte-like cells showed positivity with the KP-1 (CD-3) antibody.
C1 [Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Besznyak, Istvan] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
RP Orosz, Zs (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 75
EP 79
PG 5
ER
PT J
AU Balogh, K
Ferencz, T
Csikos, A
Timar, J
AF Balogh, Karoly
Ferencz, Tamas
Csikos, Andras
Timar, Jozsef
TI Tumoral Calcinosis in Infancy (A light and electron microscopic study with X-ray microanalysis)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE tumoral calcinosis; infancy; microanalysis
ID tumoral calcinosis; infancy; microanalysis
AB The most frequent form of idiopathic calcinosis is tumoral calcinosis (TC) which rarely occurs at young ages. We describe here a TC case of a young boy with its light microscopy completed with electron microscopic examinations. X-ray microanalysis revealed in the intracellular crystals CaCl2 besides the previously described hydroxyapatite. The significance of this finding is unknown at the moment.
C1 [Balogh, Karoly] Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Pathology and Laboratory Medicine, 185 Pilgrim Rd., 02215 Boston, MA, USA.
[Ferencz, Tamas] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Csikos, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Balogh, K (reprint author), Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Pathology and Laboratory Medicine, 02215 Boston, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 80
EP 84
PG 5
ER
PT J
AU Timar, J
Jeney, A
Kovalszky, I
Kopper, L
AF Timar, Jozsef
Jeney, Andras
Kovalszky, Ilona
Kopper, Laszlo
TI Role of Proteoglycans in Tumor Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE proteoglycan; metastasis; glycosaminoglycan; invasion
ID proteoglycan; metastasis; glycosaminoglycan; invasion
AB Data is now starting to accumulate on the differential expression of PGs in tumor cells of various invasive/metastatic potential. This is not so surprising if one considers the key functions that PGs play in the regulation of cell proliferation, adhesion and motility. However, characterization of PG expression in individual tumor types still awaits further detailed studies. Data on melanomas clearly indicate that PG phenotype is both specific and also promiscuous in a sense that ectopic expression of certain tissue specific PGs can occur in various tumors. Expression of a metastatic phenotype-specific splice variants of CD44 provides an example for the possible marker-function of PG. This also raises the hope that some PGs could be used as diagnostic/prognostic tools in pathology or even as a therapeutic targets against tumor dissemination. On the other hand, specific glycanation inhibitors may also be used for the modulation of tumor PG exist and the invasive phenotype.
C1 [Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1995
VL 1
IS 1
BP 85
EP 93
PG 9
ER
PT J
AU Isaacson, GP
AF Isaacson, G Peter
TI Primary Gastric Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE MALT; gastric lymphoma
ID MALT; gastric lymphoma
AB The pathogenesis of gastric MALT lymphoma starts with accumulation of MALT following infection of the stomach by H. pylori. Rarely this lymphoid infiltrate contains cells with a growth advantage possibly due to a genetic change (trisomy 3?). The result is a monoclonal lymphoproliferative lesion which is responsive to H. pylori driven T-cell help. Because its growth is dependent on the presence of local antigen, gastric MALT lymphoma remains localized for long periods and it is during this phase that the lymphoma can be treated by eradication of H. pylori. Further genetic changes, as yet uncharacterized may lead to escape from T-cell dependency and ultimately high grade transformation.
C1 [Isaacson, G Peter] University College London Medical School, Department of Histopathology, University Street, WC1 E 6JJ London, UK.
RP Isaacson, GP (reprint author), University College London Medical School, Department of Histopathology, WC1 E 6JJ London, UK.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 5
EP 10
PG 6
ER
PT J
AU Strausz, J
AF Strausz, Janos
TI Lung Cancer: A Bronchoscopic Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lung cancer; bronchoscopy; diagnosis; therapy
ID lung cancer; bronchoscopy; diagnosis; therapy
AB The unfavorable epidemiological data of lung cancer has not been changed during the past ten years. The only possibility to cure this malignancy is surgical resection. The five year survival rate after surgery is highly dependent on early discovery of the tumor. Today, bronchoscopy plays a central role in the diagnosis, staging and therapy of lung cancer. The main indications of diagnostic bronchoscopy are the identification of the tumor and the determination of its extent. The aim of therapeutic bronchoscopy - laser photocoagulation, high dose rate afterloading irradiation and stent implantation - is to provide an acceptable quality of life and to manage symptoms such as bleeding, cough and dyspnea.
C1 [Strausz, Janos] National Koranyi Institute for TB and Pulmonology, Department of Pulmonology, Piheno u. 1., H-1529 Budapest, Hungary.
RP Strausz, J (reprint author), National Koranyi Institute for TB and Pulmonology, Department of Pulmonology, H-1529 Budapest, Hungary.
EM str12196@helka.iif.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 11
EP 15
PG 5
ER
PT J
AU Rot, A
AF Rot, Antal
TI Inflammatory and Physiological Roles of Chemokines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE IL-8; MCP-1; RANTES; inflammation; sweat; milk; leukocytes
ID IL-8; MCP-1; RANTES; inflammation; sweat; milk; leukocytes
AB Chemokines, members of the family of chemotactic peptides, have a well documented function in different inflammatory diseases where they induce leukocyte emigration into lesions. Several recent observations indicate that, in addition to pathological states, chemokines are also produced and secreted under physiological conditions by various exocrine glands in amounts sufficient for their full biological effect. The glands involved in chemokine production and secretion include eccrine sweat glands, lactating mammary glands, lacrimal and salivary glands. It is suggested that analogous to their role in inflammatory diseases, chemokines produced by the exocrine glands are responsible for the induction of homeostatic leukocyte migration into mucosal epithelia and skin and also, mammary glands and milk. In addition, the mechanism by which chemokines induce leukocyte homing under physiological circumstances is discussed.
C1 [Rot, Antal] Sandoz Research Institute, Department of Dermatology, Experimental Molecular Pathology, Brunner Str. 59., A-1235 Vienna, Austria.
RP Rot, A (reprint author), Sandoz Research Institute, Department of Dermatology, Experimental Molecular Pathology, A-1235 Vienna, Austria.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 16
EP 20
PG 5
ER
PT J
AU Tang, GD
Diglio, AC
Honn, K
AF Tang, G Dean
Diglio, A Clement
Honn, Kenneth
TI Tyrosine Phosphorylation of a ~30 kD Protein Precedes avb3 Integrin-signaled Endothelial Cell Spreading and Motility on Matrix Proteins
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE integrin; motility; spreading; tyrosin phosphorylation; extracellular matrix
ID integrin; motility; spreading; tyrosin phosphorylation; extracellular matrix
AB A microvascular endothelial cell line (CD clone 4) isolated from murine lung adheres to and spreads well on fibronectin, vitronectin, and fibrinogen, but poorly on collagen type IV and laminin. Ligating cell surface av, b3, a4, a5, or b1 integrin receptors with monospecific antibodies promoted a dramatic cell spreading and motility on vitronectin or collagen IV. Antibodies directed to other adhesion molecules, including aIIb, PECAM-1, and P-selectin were ineffective. Ligation with monoclonal anti-av or -b3, but not -a4, -a5, or -b1 antibodies, induced a rapid, and dose-dependent tyrosine phosphorylation of a ~30 kD protein, which preceded CD clone 4 endothelial cell spreading and motility and was partially inhibited by genistein and completely inhibited by BAPTA. All other antibodies tested did not induce the tyrosine phosphorylation of the 30 kD protein as well as cell spreading and motility. The present results suggest that b1 and b3 integrins employ different biochemical mechanisms in signaling endothelial cell spreading and motility and that the tyrosine phosphorylation of the 30 kD protein (and probably other proteins) may play an important role in signaling b3 integrin-mediated endothelial cell interaction with other cells (e.g., tumor cells) and extracellular matrix.
C1 [Tang, G Dean] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Diglio, A Clement] Wayne State University, Department of PathologyDetroit, USA.
[Honn, Kenneth] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
RP Honn, K (reprint author), Wayne State University, Department of Radiation Oncology, 48202 Detroit, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 21
EP 29
PG 9
ER
PT J
AU McDonald, SJ
Wilson, MK
Gartside, P
Sonke, LR
Pavelic, L
Okum, E
Neanen, J
Gluckman, LJ
Pavelic, PZ
AF McDonald, S John
Wilson, M Keith
Gartside, Peter
Sonke, L Robert
Pavelic, Ljiljana
Okum, Eric
Neanen, Julie
Gluckman, L Jack
Pavelic, P Zlatko
TI Immunohistochemical Expression of N-ras Oncogene is a Late Event in Head and Neck Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck cancer; immunohistochemistry; N-ras
ID head and neck cancer; immunohistochemistry; N-ras
AB This study investigated the expression of the N-ras oncogene in routinely processed tissue sections from 133 patients with squamous cell carcinoma of the head and neck (SCCHN) by immunohistochemistry using anti-N-ras monoclonal antibody. N-ras expression was present in 67 of 133 (49.6%) cases. There was a highly significant correlation between N-ras expression and clinical stage of disease (P=0.003). This study confirmed that overexpression of the N-ras oncogene is common in SCCHN and that it may be an important event in the late stage of disease.
C1 [McDonald, S John] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
[Wilson, M Keith] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
[Gartside, Peter] University of Cincinnati College of Medicine, Department of Environmental HealthCincinnati, Ohio, USA.
[Sonke, L Robert] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
[Pavelic, Ljiljana] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
[Okum, Eric] Ohio State University, Medical SchoolColumbus, Ohio, USA.
[Neanen, Julie] Ohio State University, Medical SchoolColumbus, Ohio, USA.
[Gluckman, L Jack] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
[Pavelic, P Zlatko] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, Ohio, USA.
RP Pavelic, PZ (reprint author), University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45167-0528 Cincinnati, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 30
EP 33
PG 4
ER
PT J
AU McDonald, SJ
Gartside, SP
Pavelic, JL
Gluckman, LJ
Pavelic, PZ
AF McDonald, S John
Gartside, S Peter
Pavelic, J Ljiljana
Gluckman, L Jack
Pavelic, P Zlatko
TI nm23-H1 Expression in Squamous Cell Carcinoma of the Head and Neck
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck cancer; nm23-H1 gene expression; immmunohistochemistry; prognosis
ID head and neck cancer; nm23-H1 gene expression; immmunohistochemistry; prognosis
AB Archival material from 47 patients with primary squamous cell carcinoma of the head and neck (SCCHN) was studied immunohistochemically for the presence of nm23-H1 protein. Our data indicate that nm23-H1 protein expression is a common event in SCCHN and that there is a trend toward correlation of increased expression of nm23-H1 with increasing tumor size (p = 0.072). The results also show that when adjusting for age and cause of death, there tended to be an inverse relationship between overall survival and the expression of nm23-H1 gene in the primary tumor (p = 0.088).
C1 [McDonald, S John] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, Ohio, USA.
[Gartside, S Peter] University of Cincinnati College of Medicine, Department of Environmental HealthCincinnati, Ohio, USA.
[Pavelic, J Ljiljana] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, Ohio, USA.
[Gluckman, L Jack] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, Ohio, USA.
[Pavelic, P Zlatko] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, Ohio, USA.
RP Pavelic, PZ (reprint author), University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 34
EP 36
PG 3
ER
PT J
AU Piffko, J
Bankfalvi,
Ofner, D
Totsch, M
Berens, A
Joos, U
Bocker, W
Schmid, WK
AF Piffko, Jozsef
Bankfalvi, Agnes
Ofner, Dietmar
Totsch, Martin
Berens, Axel
Joos, Ulrich
Bocker, Werner
Schmid, Werner Kurt
TI Proliferative (MIB1, mdm2) Versus Anti-Proliferative (p53) Markers in Head and Neck Cancer. An Immunohistochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; mdm2; MIB1; immunohistochemistry; wet autoclave pretreatment; head and neck cancer
ID p53; mdm2; MIB1; immunohistochemistry; wet autoclave pretreatment; head and neck cancer
AB Formalin fixed and paraffin embedded samples from 36 squamous cell carcinomas of the larynx and the oral cavity (pT2N0M0, R0) surrounded by non-tumorous mucosa were studied immunohistochemically using a panel of four different anti-p53 antibodies (CM1, PAb1801, D07, PAb240), a monoclonal anti-mdm2 antibody and MIB1, following wet autoclave antigen retrieval. P53 immunoreactivity was detected in 11/14 laryngeal and in 9/22 oral carcinomas. All p53 positive oral, and all but one laryngeal tumors revealed mdm2 positivity as well, whereas in p53 negative tumors 4/12 and 1/3 mdm2 immunopositive cases were demonstrated, respectively. MIB1 labeling indices of the tumors ranged between 18% - 64% in p53 positive cases, and 10% - 53% in p53 negative ones. The difference was not statistically significant. Close spatial coexpression of p53, mdm2 and MIB1 immunoreactivity was observed at the invasive front of the carcinomas and in the basal and suprabasal layers of the non-tumorous epithelium in all p53 positive cases. However, the MIB1 expression was similarly increased at the invasive margins in carcinomas lacking immunohistochemically detectable p53 alterations. Our results strongly suggest that p53 overexpression does not necessarily correspond to increased rate of proliferation, but rather to mdm2 overexpression and is largely dependent on the anatomical site in case of small and localized squamous cell carcinomas of the head and neck region.
C1 [Piffko, Jozsef] University of Munster, Department of Cranio-Maxillofacial SurgeryMunster, Germany.
[Bankfalvi, Agnes] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
[Ofner, Dietmar] University Hospital, Department of Surgery IInnsbruck, Austria.
[Totsch, Martin] Medical University of Innsbruck, Department of PathologyInnsbruck, Austria.
[Berens, Axel] University of Munster, Department of Cranio-Maxillofacial SurgeryMunster, Germany.
[Joos, Ulrich] University of Munster, Department of Cranio-Maxillofacial SurgeryMunster, Germany.
[Bocker, Werner] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
[Schmid, Werner Kurt] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
RP Schmid, WK (reprint author), University of Munster, Department of Pathology, D-48149 Munster, Germany.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 37
EP 42
PG 6
ER
PT J
AU Repassy, G
Czigner, J
Ribari, O
AF Repassy, Gabor
Czigner, Jeno
Ribari, Otto
TI Glottic Cancer of the Free Margin and Ventricular Surface of Vocal Cord
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glottic cancer; intralaryngeal spread; histopathology
ID glottic cancer; intralaryngeal spread; histopathology
AB The authors differentiate cancer types of the glottis setting out from the free margin or the ventricular surface of the true vocal cord. The latter is considered to be a reliant clinicopathological unit starting from the dividing line of the stratified-ciliated epithelium margins, whereas the so called junctional tumor differs in its histogenesis and invasivity. They give a detailed description of intralaryngeal extension of these tumours on the basis of histopathological investigations.
C1 [Repassy, Gabor] Medical University, Department of Oto-Rhino-Laryngology, Nagyerdei krt 98., H-4012 Debrecen, Hungary.
[Czigner, Jeno] Szegedi Tudomanyegyetem, Ful-Orr-Gegeszeti KlinikaSzeged, Hungary.
[Ribari, Otto] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
RP Repassy, G (reprint author), Medical University, Department of Oto-Rhino-Laryngology, H-4012 Debrecen, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 43
EP 47
PG 5
ER
PT J
AU Sztan, M
Besznyak, I
Kovacs, T
Toth, J
Szamel, I
Olah, E
AF Sztan, Marianna
Besznyak, Istvan
Kovacs, Tibor
Toth, Jozsef
Szamel, Iren
Olah, Edit
TI Lack of Correlation Between Survival and Allele Loss on Chromosome 7q31-32 in Primary Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chromosome 7q; tumor suppressor gene; loss of heterozygosity; primary breast carcinoma
ID chromosome 7q; tumor suppressor gene; loss of heterozygosity; primary breast carcinoma
AB High incidence of loss of heterozygosity (LOH), affecting the 7q31-32 chromosome region in sporadic primary human breast carcinomas suggests the presence of a tumor suppressor gene in this region which seems relevant to the development of breast cancer. To further determine the possible role of this region in the pathogenesis of human primary breast cancer and association with survival, LOH analysis was performed on 52 primary breast cancer patients using a set of highly polymorphic microsatellite markers. Our panel contained twenty biopsy cases of unknown survival, nineteen cases with more than five years survival and fourteen cases with less than two years survival. Corresponding normal and tumor DNAs were analyzed by polymerase chain reaction (PCR). The data presented here demonstrate that all patients were informative at least at one locus and 20 (38%) out of 53 cases showed LOH at one or more loci on chromosome 7q31-32. Relatively high incidence of LOH (34%) was detected at the D7S522 microsatellite marker located near to the cMet proto-oncogene while lower frequencies were observed at D7S523 (19%) and D7S495 (17%) loci, supporting the existence of a putative tumor suppressor gene at the chromosome 7q31.1 region. Our results suggest that allelic imbalance on 7q may occur at an early stage of breast carcinogenesis, as no correlation was observed between allelic loss and clinico-pathological data.
C1 [Sztan, Marianna] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7., H-1525 Budapest, Hungary.
[Besznyak, Istvan] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Kovacs, Tibor] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Toth, Jozsef] National Institute of Oncology, Department of Diagnostic PathologyBudapest, Hungary.
[Szamel, Iren] National Institute of Oncology, Department of Clinical ResearchBudapest, Hungary.
[Olah, Edit] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7., H-1525 Budapest, Hungary.
RP Olah, E (reprint author), National Institute of Oncology, Department of Biochemistry, H-1525 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 48
EP 51
PG 4
ER
PT J
AU Kozma, L
Papp, L
Varga,
Gomba, Sz
AF Kozma, Laszlo
Papp, Lajos
Varga, Eva
Gomba, Szabolcs
TI Accumulation of Hg(II) Ions in Mouse Adrenal Gland
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hg(II); acute intoxication; adrenal gland; atomic absorption spectroscopy; autometallography
ID Hg(II); acute intoxication; adrenal gland; atomic absorption spectroscopy; autometallography
AB Female BALBc mice were administered HgCl2 at a single dose of 4 mg/kg i.p. The acute intoxication with Hg(II) salts (2 hr) caused accumulation of Hg(II) ions in the adrenal gland in general, and in the medulla, in particular. Based on data obtained with atomic absorption spectroscopy and quantitative cytochemistry, we determined the amount of mercury (II) in the adrenal glands and found it to be 14.2 ng Hg(II) (3.5 mg/kg wet weight of the adrenals). An uneven distribution of Hg(II) was found within the adrenal gland, not only between the medulla and cortex, but also within the cortex. The applied autometallographic method revealed that the cortex was negative except the zona glomerulosa, whereas the medulla showed a strong reaction localised to the chromaffin granules of the secretory cells. Both adrenaline and noradrenaline producing cells reacted. The comparison of the density of silver grains by scanning densitometry in the medulla and cortex revealed a significantly higher Hg(II) concentration in the medulla compared to the cortex (10 mg/kg vs 2 mg/kg, respectively). The results presented here suggest that there may be a connection between the symptoms of acute Hg(II) intoxication and its adrenal accumulation.
C1 [Kozma, Laszlo] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
[Papp, Lajos] Lajos Kossuth University, Department of Inorganic and Analytical ChemistryDebrecen, Hungary.
[Varga, Eva] Hungarian-Japanese Electron Microscopic CenterDebrecen, Hungary.
[Gomba, Szabolcs] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
RP Kozma, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 1996
VL 2
IS 1
BP 52
EP 55
PG 4
ER
PT J
AU Kovalszky, I
Schaff, Zs
Lapis, K
Jeney, A
AF Kovalszky, Ilona
Schaff, Zsuzsa
Lapis, Karoly
Jeney, Andras
TI Marker Enzymes of Rat Chemical Hepatocarcinogenesis in Human Liver Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE liver tumor; GGT; G-6-Pase; cytochrome P-450
ID liver tumor; GGT; G-6-Pase; cytochrome P-450
AB Reduced glucose-6-phosphatase, increased GGT activity and reduction of cytochrome P-450 content are considered to be markers of chemical hepatocarcinogenesis in rats. The significance of these changes were studied in certain human liver lesions; adenoma, focal nodular hyperplasia and hepatocellular carcinoma all developed in non-cirrhotic livers. Enzymes showed normal values in 4 out of 5 adenomas, in 2/13 FNH and in 4/18 HCC samples. The decreased cP-450 content in HCC proved to be the most consistent alteration (12/18). Only 3 HCC samples possessed changes off all enzymes. These data suggest that at least those enzymes which are used as markers in rat chemical hepatocarcinogenesis have little or no biological significance in human liver tumors, primarily due to the intertumoral heterogeneity of enzyme activity. Such heterogeneity was observed in the peritumoral ''normal'' liver tissue, too.
C1 [Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Lapis, Karoly] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM koval@korb1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 56
EP 58
PG 3
ER
PT J
AU Horvath, G
Stotz, Gy
Tolvaj, Gy
Osztrogonacz, H
David, K
AF Horvath, Gabor
Stotz, Gyula
Tolvaj, Gyula
Osztrogonacz, Henrik
David, Karoly
TI The Effect Of Long Term and High Dose Interferon Treatment In Chronic Hepatitis C
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic hepatitis C; interferon treatment
ID chronic hepatitis C; interferon treatment
AB The results of 43 interferon treatments of 35 patients (23 male, 12 female) are reported. The duration of the treatment was 6-18 months, the dose of interferon was 3x3-5 MU weekly. Complete response (HCV RNA became negative) was found in 11, relapse was observed in 3 patients. Partial response (transaminase levels became normal, or less than twice normal value, but patients remained HCV RNA positive) occurred in 23 cases, relapse was obeserved in 16. The therapy had no effect in 9 cases. The higher dose and longer term interferon therapy resulted in a higher rate of response to the treatment and a reduction in the number of relapses.
C1 [Horvath, Gabor] Central Hospital of the Ministry of the Interior, 1st Department of Medicine, Budakeszi ut 48/b, 1121 Budapest, Hungary.
[Stotz, Gyula] Central Hospital of the Ministry of the Interior, Department of PathologyBudapest, Hungary.
[Tolvaj, Gyula] Central Hospital of the Ministry of the Interior, 1st Department of Medicine, Budakeszi ut 48/b, 1121 Budapest, Hungary.
[Osztrogonacz, Henrik] Central Hospital of the Ministry of the Interior, 1st Department of Medicine, Budakeszi ut 48/b, 1121 Budapest, Hungary.
[David, Karoly] Central Hospital of the Ministry of the Interior, 1st Department of Medicine, Budakeszi ut 48/b, 1121 Budapest, Hungary.
RP Horvath, G (reprint author), Central Hospital of the Ministry of the Interior, 1st Department of Medicine, 1121 Budapest, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 59
EP 62
PG 4
ER
PT J
AU Benfares, J
Le Tourneau, A
Audouin, J
Szekeres, Gy
AF Benfares, Jamal
Le Tourneau, Agnes
Audouin, Josee
Szekeres, Gyorgy
TI Effect of Ribonuclease A and Deoxyribonuclease I on Immunostaining of Ki-67 in Cultured Melanoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ki-67; immunocytochemistry; enzymatic pre-digestion; proliferating cells
ID Ki-67; immunocytochemistry; enzymatic pre-digestion; proliferating cells
AB Immunostaining of the cell cycle-associated Ki-67 antigen was studied, using the Ki-67-specific MIB-1 monoclonal antibody on slides prepared by cytocentrifugation of cultured A375 melanoma cells. Immunomorphological analysis of the Ki-67 immunostaining pattern of both nuclear and nucleolar locations was carried out following pre-treatment of the slides including ribonuclease and deoxyribonuclease pre-digestion of the cells. Immunostaining of nucleolar Ki-67 was reduced by ribonuclease pre-digestion, but was not altered by deoxyribonuclease pre-treatment. Ribonuclease did not reduce the staining intensity of Ki-67 in the nuclear matrix, but the intensity decreased after deoxyribonuclease pre-digestion. We suggest that the Ki-67 molecule may play an important role in ensuring contact between nuclear DNA and nucleolar RNA during transcriptional processes in cell proliferation.
C1 [Benfares, Jamal] Immunotech, Antibody Department, R&D LaboratoryMarseille, France.
[Le Tourneau, Agnes] Hotel-Dieu, Laboratory of PathologyParis, France.
[Audouin, Josee] Hotel-Dieu, Laboratory of PathologyParis, France.
[Szekeres, Gyorgy] Hisztopatologia KFT, Akac u. 8., H-7632 Pecs, Hungary.
RP Szekeres, Gy (reprint author), Hisztopatologia KFT, H-7632 Pecs, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 63
EP 65
PG 3
ER
PT J
AU Hrzenjak, MT
Roguljic, A
Efenberger-Marinculic, P
Popovic, M
Pisl, Z
AF Hrzenjak, M Terezija
Roguljic, Ante
Efenberger-Marinculic, Palma
Popovic, Maja
Pisl, Zoran
TI Total IgA and IgG in Sera of Patients With Different Primary Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IgA; IgG; malignant tumors
ID IgA; IgG; malignant tumors
AB The concentrations of total serum IgA and IgG of 267 patients with different primary malignant tumors were measured by ELISA. Total serum IgA increased by 30% to 40% in patients with malignancies associated with mucous membranes (nasopharyngeal, gastrointestinal and bronchial carcinomas), while the change in total serum IgG was negligible. Although, the changes in Ig level could be influenced by many host factors, these data call attention to the potential indicative role of total serum IgA levels. Further studies are required to establish links between serum IgA levels and stages of tumor growth or tumor progression in order to use these values as prognostic factors.
C1 [Hrzenjak, M Terezija] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55., 10000 Zagreb, Croatia.
[Roguljic, Ante] University Hospital for TumorsZagreb, Croatia.
[Efenberger-Marinculic, Palma] Institute for Medical Research and Occupational HealthZagreb, Croatia.
[Popovic, Maja] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55., 10000 Zagreb, Croatia.
[Pisl, Zoran] Institute for Medical Research and Occupational HealthZagreb, Croatia.
RP Hrzenjak, MT (reprint author), Faculty of Veterinary Medicine, Department of Biology, 10000 Zagreb, Croatia.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 66
EP 68
PG 3
ER
PT J
AU Griciute, L
Domkiene, V
AF Griciute, Laima
Domkiene, Vida
TI Experimental Study on the Carcinogenicity of the Cytostatic Drug Ftorafur (Tegafur)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ftorafur; Tegafur; carcinogenicity; mouse; rat
ID Ftorafur; Tegafur; carcinogenicity; mouse; rat
AB Long-term carcinogenicity of Ftorafur (Tegafur) was studied in rodents. Rats and mice were treated for one year per os with 40 (mice) and 60 (rat) mg/kg Ftorafur twice a week and were followed for their entire life. Analysis of the data provide no evidence for the carcinogenicity of Ftorafur in rodents. These findings are similar to other antimetabolite studies and contrasts with the carcinogenic alkylating agents.
C1 [Griciute, Laima] Lithuanian Oncology Center, Santariskiy 1., 2600 Vilnius, Lithuania.
[Domkiene, Vida] Lithuanian Oncology Center, Santariskiy 1., 2600 Vilnius, Lithuania.
RP Griciute, L (reprint author), Lithuanian Oncology Center, 2600 Vilnius, Lithuania.
EM onko.centras@loc.lt
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 69
EP 70
PG 2
ER
PT J
AU Bankfalvi,
Piffko, J
Ofner, D
Dreier, R
Bocker, W
Schmid, WK
AF Bankfalvi, Agnes
Piffko, Jozsef
Ofner, Dietmar
Dreier, Rita
Bocker, Werner
Schmid, Werner Kurt
TI Significance of Wet Autoclave Pretreatment in Immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE Wet autoclave pretreatment; Immunohistochemistry; AgNOR
ID Wet autoclave pretreatment; Immunohistochemistry; AgNOR
AB Until recently the only way to rescue masked epitopes in routinely processed surgical pathological material was enzymatic digestion. The use of heat for antigen retrieval, first by microwave irradiation, represents an important breakthrough in immunohistochemistry. With the acceptance of microwave oven pretreatment, various modified techniques and alternative heating methods have also been proposed. Wet autoclave pretreatment for tissue proteolysis is a highly reliable alternative to the microwave antigen retrieval technique. It provides uniform heating of the slides, hence an even enhancement of staining intensity in a variety of formalin-sensitive antigens, and it also offers consistent interlaboratory results. The method has been introduced in routine diagnostic immunohistochemistry for the detection of estrogen- and progesterone receptors, L26-, Ki-67- and bcl-2 antigens and variable types of cytokeratins (1/5/10/11, 8, 13, 19). Experimentally, wet autoclaving can be used very successfully for the immunophenotyping of p53 and mdm2 expression, for the detection of adhesion molecules (CD44, integrins) and some anti-inflammatory molecules (annexins), among others. It has produced a substantial improvement in the visualisation of silver-stained nucleolar organizer regions- associated proteins (AgNORs) in routine paraffin sections and along with modified silver staining and standardized AgNOR parameters assessed by image analysis. Wet autoclaving-based AgNOR staining has been proposed by a European multicentric study group as the standardized method for AgNOR analysis in archival material.
C1 [Bankfalvi, Agnes] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
[Piffko, Jozsef] University of Munster, Department of Cranio-Maxillofacial SurgeryMunster, Germany.
[Ofner, Dietmar] University Hospital, Department of Surgery IInnsbruck, Austria.
[Dreier, Rita] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
[Bocker, Werner] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
[Schmid, Werner Kurt] University of Munster, Department of Pathology, Domagkstrasse 17, D-48149 Munster, Germany.
RP Schmid, WK (reprint author), University of Munster, Department of Pathology, D-48149 Munster, Germany.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 71
EP 77
PG 7
ER
PT J
AU Mihalik, R
Uher, F
Pocsik,
Berczi, L
Benczur, M
Kopper, L
AF Mihalik, Rudolf
Uher, Ferenc
Pocsik, Eva
Berczi, Lajos
Benczur, Miklos
Kopper, Laszlo
TI Detection of Drug-induced Apoptosis by Flow Cytometry after Alkaline Extraction of Ethanol Fixed Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE apoptosis; cell cycle; drug-induced; DNA extraction; flow cytometry
ID apoptosis; cell cycle; drug-induced; DNA extraction; flow cytometry
AB A new flow cytometric method was developed to detect apoptotic cells with fragmented DNA and to determine cell cycle distribution of viable cells, in the same sample, by propidium iodide staining. Apoptosis, in HT58 human B lymphoma cells, was induced by etoposide and/or by staurosporine. Using appropriate alkaline solutions (between 1-10 mN NaOH in 150 mM saline) followed by neutralization with buffer solution, the fragmented DNA can be extracted quantitatively from ethanol fixed cells. Further, good resolution of the cell cycle distribution can be obtained in unimpaired cells without RNase treatment. Furthermore, unlike the widely used hypotonic-detergent extraction of unfixed cells, the suggested extraction method can prevent drug-induced disintegration of dead cells when karyorrhexis occurs.
C1 [Mihalik, Rudolf] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Uher, Ferenc] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Pocsik, Eva] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Berczi, Lajos] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Benczur, Miklos] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 78
EP 83
PG 6
ER
PT J
AU Orosz, Zs
Toth, E
Viski, A
AF Orosz, Zsolt
Toth, Erika
Viski, Anna
TI Osteoclastoma-like Giant Cell Tumor of the Lung
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE osteoclast-like giant cells; giant cell tumor; lung; p53; PCNA
ID osteoclast-like giant cells; giant cell tumor; lung; p53; PCNA
AB The main components of an unusual form of lung tumor were osteoclast-like multinucleated giant cells and mononuclear stromal cells. Besides, scattered islands of moderately differentiated squamous cells also appeared. Both the mononuclear and the osteoclast-like giant cells reacted with antibodies against CD68 and vimentin, but did not react with antibodies against cytokeratin, EMA and CEA, or lysozyme and a-1-antitrypsin. The p53 and PCNA antigens were positive only in mononuclear cells and not the osteoclast-like giant cells, suggesting that mononuclear cells represent proliferating elements with histiocytic differentiation while osteoclast-like giant cells are stromal, presumably reactive components of the tumor.
C1 [Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gyorgy u. 7-9., 1122 Budapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Viski, Anna] Kaposi Mor Hospital, Department of PathologyKaposvar, Hungary.
RP Orosz, Zs (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, 1122 Budapest, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 84
EP 88
PG 5
ER
PT J
AU Toth, J
Kerenyi,
Suveges, I
Futo, G
AF Toth, Jeannette
Kerenyi, Agnes
Suveges, Ildiko
Futo, Gabor
TI Leiomyoma of The Ciliary Body and Hemangiopericytoma of the Choroid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE intraocular non-melanocytic tumors; leiomyoma; hemangiopericytoma
ID intraocular non-melanocytic tumors; leiomyoma; hemangiopericytoma
AB Two unusual uveal tumors occurring in eyes enucleated for presumed malignant melanoma are discussed. One was a leiomyoma of the ciliary body, affecting a 22-year-old female, the other a hemangiopericytoma of the choroid in an 84-year-old male patient. The latter case is the fourth intraocular hemangiopericytoma reported in the literature to date. The histopathologic diagnosis was confirmed by immunohistochemistry and electron microscopy.
C1 [Toth, Jeannette] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29., 1083 Budapest, Hungary.
[Kerenyi, Agnes] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29., 1083 Budapest, Hungary.
[Suveges, Ildiko] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29., 1083 Budapest, Hungary.
[Futo, Gabor] Szent Borbala Hospital, Department of OphthalmologyTatabanya, Hungary.
RP Toth, J (reprint author), Semmelweis University, Department of Ophthalmology, 1083 Budapest, Hungary.
EM tj@szem1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 89
EP 93
PG 5
ER
PT J
AU Patonai, A
Csikos, A
Deak, Gy
AF Patonai, Attila
Csikos, Andras
Deak, Gyorgy
TI Visceral Aluminum Deposition In Chronic Renal Insufficiency (Light Microscopy and X-ray Microanalysis)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE aluminum; renal insufficency; myocardium; lung; kidney
ID aluminum; renal insufficency; myocardium; lung; kidney
AB Aluminum is a common element in our environment, but has been proved to be toxic, mainly in chronic renal insufficiency. Most cases of ALU intoxication occur during hemodialysis due to treatment of aluminum-containing drugs. In the present case, we describe visceral manifestations of aluminum deposition in a middle aged, multidialysed, male patient. Light and polarization microscopy examinations and X-ray microanalysis revealed amorph, extracellular aluminum deposits in various parenchymal organs causing failure of heart, lung and kidney functions. There were no anamnestic data concerning aluminum-containing drugs or occupational exposure.
C1 [Patonai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Csikos, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Deak, Gyorgy] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
RP Patonai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM patonai@korb1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 94
EP 97
PG 4
ER
PT J
AU Honn, VK
Aref, A
Chen, QY
Cher, LM
Crissman, DJ
Forman, DJ
Gao, X
Grignon, D
Hussain, M
Porter, TA
Pontes, E
Powell, I
Redman, B
Sakr, W
Severson, R
Tang, GD
Wood, PD
AF Honn, V Kenneth
Aref, Amer
Chen, Q Yong
Cher, L Michael
Crissman, D John
Forman, D Jeffrey
Gao, Xiang
Grignon, David
Hussain, Maha
Porter, T Arthur
Pontes, J. Edson
Powell, Isaac
Redman, Bruce
Sakr, Wael
Severson, Richard
Tang, G Dean
Wood, P David
TI Prostate Cancer, Old Problems and New Approaches Part I.
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE prostate cancer; epidemiology; incidence; genetics; progression
ID prostate cancer; epidemiology; incidence; genetics; progression
AB Rates of prostate cancer (PCa) have increased so dramatically over the last decade that the age adjusted incidence rate for PCa is now greater than that any other cancer among men in the United States. This review, published as a three part series, provides a state-of-art assessment of the PCa problem in its divergent aspects. Part 1 covers epidemiology, incidence and progression. Several epidemiological studies have demostrated that first degree male relatives of men with PCa are at increased risk of developing the disease. Familial and genetic factors as well as medical, anthropometric, dietary, hormonal and occupational factors involved in PCa are discussed. Postmortem examination of the prostate in men without evidence of PCa documented a high frequency of adenocarcinoma. Latent disease occurred as early as the second decade of life. Although there is no significant difference in incidence between Caucasian and African-American males, high grade prostatic intraepithelial neoplasia (HGPIN) is higher in the latter group. While dietary fat, androgens and certain environmental factors may be determinants for PCa, the exact mechanism of tumorigenesis is still relatively unknown. The current thinking of the role of genomic instability, chromosomal alterations, tumor suppressor genes and the androgen receptor are explored.
C1 [Honn, V Kenneth] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Aref, Amer] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Chen, Q Yong] Wayne State University, Department of PathologyDetroit, USA.
[Cher, L Michael] Wayne State University, Department of UrologyDetroit, USA.
[Crissman, D John] Wayne State University, Department of PathologyDetroit, USA.
[Forman, D Jeffrey] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Gao, Xiang] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Grignon, David] Wayne State University, Department of PathologyDetroit, USA.
[Hussain, Maha] Wayne State University, Department of MedicineDetroit, USA.
[Porter, T Arthur] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Pontes, J. Edson] Wayne State University, Department of UrologyDetroit, USA.
[Powell, Isaac] Wayne State University, Department of UrologyDetroit, USA.
[Redman, Bruce] Wayne State University, Department of MedicineDetroit, USA.
[Sakr, Wael] Wayne State University, Department of PathologyDetroit, USA.
[Severson, Richard] Wayne State University, Department of Family MedicineDetroit, USA.
[Tang, G Dean] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48201 Detroit, Michigan, USA.
[Wood, P David] Wayne State University, Department of UrologyDetroit, USA.
RP Honn, VK (reprint author), Wayne State University, Department of Radiation Oncology, 48201 Detroit, USA.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1996
VL 2
IS 2
BP 98
EP 109
PG 12
ER
PT J
AU Tang, GD
Porter, TA
AF Tang, G Dean
Porter, T Arthur
TI Apoptosis: A Current Molecular Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE apoptosis; genes; review
ID apoptosis; genes; review
AB Apoptosis is a cell suicide program characterized by distinct morphological (cell shrinkage, membrane blebbing, pyknosis, chromatin margination, denser cytoplasmic images) and biochemical (e.g., DNA fragmentation into distinct ladders; degradation of apoptotic markers such as PARP and nuclear lamins) features. It is involved in multiple physiological processes examplified by involution of mammary tissues, embryonic development, homeostatic maintenance of tissues and organs, and maturation of the immune system, as well as in many pathological conditions represented by neurologic degeneration (Alzeimer's disease), autoimmune and inflammatory diseases, etiology of atherosclerosis, AIDS, and oncogenesis and tumor progression. Numerous molecular entities have been shown to regulate the apoptotic process. This review provides a concise summary of the recent data on the role of oncogenes/tumor suppressor genes, cytokines and growth factors/growth factor receptors, intracellular signal transducers, cell cycle regulators, reactive oxygen species or other free radicals, extracellular matrix regulators/cell adhesion molecules, and specific endonucleases and cytoplasmic proteases (the ICE family proteins) in regulating cell survival and apoptosis. Elucidation of the molecular mechanisms regulating apoptosis bears tremendous impact on enhancing our understanding of many diseases inflicting the human beings and undoubtedly brings us hope for the cure of these diseases.
C1 [Tang, G Dean] Wayne State University, Department of Radiation Oncology, 407 Life Science Bldg., 48202 Detroit, MI, USA.
[Porter, T Arthur] Wayne State University, Department of Radiation Oncology, 407 Life Science Bldg., 48202 Detroit, MI, USA.
RP Tang, GD (reprint author), Wayne State University, Department of Radiation Oncology, 48202 Detroit, USA.
EM dtang@cms.cc.wayne.edu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 117
EP 131
PG 15
ER
PT J
AU Schaff, Zs
Lotz, G
Schulte-Herman, R
AF Schaff, Zsuzsa
Lotz, Gabor
Schulte-Herman, Rolf
TI Pathomorphological Characteristics and Pathogenesis of Viral Hepatitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE pathomorphology; pathogenesis; viral; hepatitis
ID pathomorphology; pathogenesis; viral; hepatitis
AB Viral hepatitis (VH) is an inflammatory reaction of the liver to hepatotropic viruses. Acute VH can be classified according to the virus and type of necrosis. Chronic hepatitis (CH) might be active, persistent or lobular based on previous classification. More recently the grade (necroinflammatory activity) and stage (fibrosis and architectural distorsion) of CH have been distinguished and scored. Apoptosis and necrosis probably coexist in VH and contribute to hepatocyte death. Several ''death factors'', such as transforming growth factor b, Apo1/Fas and tumor necrosis factor play a role in the execution of cell death. Injury of hepatocytes during viral infection can occur as a direct effect of the virus or as a result of the host immune response. Expression of different viral antigens can be detected during VH and might be visualized. Phenotyping of the portal inflammatory cell infiltrate in CH has shown a T-cell zone comprised of CD4+ helper T cells and CD8+ supressor/cytotoxic T cells at the periphery of the lobules. The pathogenetic mechanisms responsible for the final outcome of viral infection depend on viral factors (such as genotype, mutation etc.), virus-host interaction, expression of viral protein, several cytokines etc. which finally lead to the well known histological alterations of viral hepatitis.
C1 [Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Schulte-Herman, Rolf] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal PathologyVienna, Austria.
RP Schaff, Zs (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 132
EP 143
PG 12
ER
PT J
AU Yamashima, T
AF Yamashima, Tetsumori
TI On Arachnoid Villi and Meningiomas: Functional Implication of Ultrastructure, Cell Adhesion Mechanisms, and Extracellular Matrix Composition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE arachnoid villus; meningioma; E-cadherin; prostaglandin D2 synthesis; multilamellar phospholipids
ID arachnoid villus; meningioma; E-cadherin; prostaglandin D2 synthesis; multilamellar phospholipids
AB Arachnoid villi or granulations are small projections of the arachnoid barrier layer into the venous sinus and its major tributaries. They are closely related to the absorption of cerebrospinal fluid, and are widely accepted to be the origin of human meningiomas. Arachnoid villi and meningiomas show a number of similarities in ultrastructure, cell adhesion mechanisms, and extracellular matrix composition. Ultrastructurally, both arachnoid and meningioma cells are characterized by interdigitations connected with junctional complexes, and extracellular cisterns related to the fluid transport. Extracellular cisterns and the intercellular space reveal abundant membrane-derived multilamellar phospholipids when a conventional ultrastructural fixative supplemented with tannic acid is used. Both arachnoid and meningioma cells are connected by Ca2+-dependent adhesion molecules: epithelial-cadherins which are concentrated at the adherens junctions. Membrane-cytoskeleton interactions by means of merlin and a-catenin molecules are thought to be crucial in signal transduction resulting in contact inhibition of cell growth in normal arachnoid cells. Impairment of these molecules might be related to meningioma-genesis. Glutathione-independent prostaglandin D2 synthase [EC 5.3.99.2] responsible for the biosynthesis of prostaglandin D2 in the central nervous system is also consistently expressed in human arachnoid villi and meningiomas. The multilamellar phospholipids are conceivably related to this arachidonate metabolism.
C1 [Yamashima, Tetsumori] Kanazawa University School of Medicine, Department of Neurosurgery, Takaramachi 13-1, 920 Kanazawa, Japan.
RP Yamashima, T (reprint author), Kanazawa University School of Medicine, Department of Neurosurgery, 920 Kanazawa, Japan.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 144
EP 149
PG 6
ER
PT J
AU Gatenby, AR
Seftor, AE
Hendrix, JM
AF Gatenby, A Robert
Seftor, A Elisabeth
Hendrix, JC Mary
TI Fibroblast Enhancement of Tumor Invasion in a Tumor-Host Interface Recapitulated in-vitro
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE invasion; cartilage; pannus; matrix metalloproteinases; cytokines
ID invasion; cartilage; pannus; matrix metalloproteinases; cytokines
AB Tumor cells and fibroblasts were isolated from the tumor-host interface of a colon 4047 tumor growing subcutaneously in a Fischer 344 rat. The populations were co-cultured to recapitulate the tumor-host interface in vitro. The co-cultured populations grew in a predictable pattern with tumor cells forming nodules surrounded by fibroblasts. Population dynamic experiments demonstrated the fibroblasts enhanced the growth of the tumor cells but tumor inhibited and ultimately destroyed the fibroblasts. Video microscopic examination of the fibroblasts demonstrated intense membrane ruffling adjacent to the tumor nodules followed by membrane fragmentation and detachment. Immunohistochemical staining for gelatinase A was markedly positive within the fibroblasts surrounding the tumor nodules; but negative within the tumor and in fibroblasts when tumor was absent. This technique recapitulates many aspects of the tumor-host interface in vitro and may be a useful model for evaluating several aspects of tumor-host interaction.
C1 [Gatenby, A Robert] Temple University Hospital, Department of Diagnostic Imaging, Broad and Ontario Streets, 19140 Philadelphia, PA, USA.
[Seftor, A Elisabeth] University of Iowa, Department of AnatomyIowa City, USA.
[Hendrix, JC Mary] University of Iowa, Department of AnatomyIowa City, USA.
RP Gatenby, AR (reprint author), Temple University Hospital, Department of Diagnostic Imaging, 19140 Philadelphia, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 151
EP 156
PG 6
ER
PT J
AU Frye, AC
Yocum, ED
Tuan, R
Suyana, E
Seftor, AE
Seftor, ER
Khalkhali-Ellis, Z
Moore, LT
Hendrix, JM
AF Frye, A Catherine
Yocum, E David
Tuan, Rocky
Suyana, Eiko
Seftor, A Elisabeth
Seftor, EB Richard
Khalkhali-Ellis, Zhila
Moore, L Terry
Hendrix, JC Mary
TI An in vitro Model for Studying Mechanisms Underlying Synoviocyte-Mediated Cartilage Invasion in Rheumatoid Arthritis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE invasion; cartilage; pannus; matrix metalloproteinases; cytokines
ID invasion; cartilage; pannus; matrix metalloproteinases; cytokines
AB Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloproteinase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be ''converted'' to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by culturing these cells in the presence of 5 U/ml IL-1b or 18 U/ml TGFb. Invasion was inhibited by 150 U/ml TNFa, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn's) did not augment invasion to the same degree. Moreover, this ''conversion effect'' appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-mediated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.
C1 [Frye, A Catherine] University of Arizona, Department of Microbiology and ImmunologyTucson, USA.
[Yocum, E David] University of Arizona, Department of RheumatologyTucson, USA.
[Tuan, Rocky] Thomas Jefferson University, Department of Orthopaedic SurgeryPhiladelphia, USA.
[Suyana, Eiko] Thomas Jefferson University, Department of Orthopaedic SurgeryPhiladelphia, USA.
[Seftor, A Elisabeth] Saint Louis University, School of Medicine, Departments of Pediatrics and Internal MedicineSt. Louis, USA.
[Seftor, EB Richard] Saint Louis University, School of Medicine, Departments of Pediatrics and Internal MedicineSt. Louis, USA.
[Khalkhali-Ellis, Zhila] Saint Louis University, School of Medicine, Departments of Pediatrics and Internal MedicineSt. Louis, USA.
[Moore, L Terry] Saint Louis University, School of Medicine, Departments of Pediatrics and Internal MedicineSt. Louis, USA.
[Hendrix, JC Mary] Saint Louis University, School of Medicine, Departments of Pediatrics and Internal MedicineSt. Louis, USA.
RP Hendrix, JM (reprint author), Saint Louis University, School of Medicine, Departments of Pediatrics and Internal Medicine, St. Louis, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 157
EP 166
PG 10
ER
PT J
AU Gergely, P
Vertesi, Cs
AF Gergely, Peter
Vertesi, Csaba
TI Urinary Excretion of Thioamine Compounds in Patients with Malignant Tumors and Inflammation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE urinary thioamine; tumor; inflammation
ID urinary thioamine; tumor; inflammation
AB The Kokonov's reaction measures thioamine-like compounds excreted in the urine. We compared the results obtained by this reaction in patients with malignant tumors and inflammatory diseases. The majority of patients with advanced (stage III-IV) cancer displayed a positive test. The chance of obtaining a positive test was related to the tumor mass. Lymphoma patients in complete remission were negative. Patients suffering from bacterial infections, active autoimmune diseases, and acute pancreatitis or myocardial infarction also had positive tests. The increased excretion of thioamines, found in tumor-bearing patients can be explained by the activation of the immune system, probably by the inflammation around or within the tumor tissue. The Kokonov's reaction is not suitable to discriminate between tumor-bearing patients and healthy ones. It rather seems to be appropriate to assess inflammatory processes in infections and/or autoimmune diseases.
C1 [Gergely, Peter] Semmelweis University, Department of Laboratory Medicine, Ulloi ut 26., H-1085 Budapest, Hungary.
[Vertesi, Csaba] Chinoin Pharmacological and Chemical Works Co. Ltd.Budapest, Hungary.
RP Gergely, P (reprint author), Semmelweis University, Department of Laboratory Medicine, H-1085 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 167
EP 170
PG 4
ER
PT J
AU Patyanik, M
Mayer,
Ungar, L
Polgar, I
AF Patyanik, Mihaly
Mayer, Arpad
Ungar, Laszlo
Polgar, Istvan
TI Early Experiences with Combined Treatment (Surgery and Brachytherapy) of Gynecological Recurrences Infiltrating the Pelvic Wall
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pelvic side wall relapses; combined operative and radiotherapeutic treatment
ID pelvic side wall relapses; combined operative and radiotherapeutic treatment
AB Neither the surgical nor the radiotherapeutic treatment of gynecological recurrences infiltrating the pelvic wall can be curative alone. The treatment of this group of patients is possible with the CORT (Combined Operative and Radiotherapeutic Treatment) method. As maximal as possible resection of the malignancy is done for patients having no distant metastases and the brachytherapy guiding tubes are implanted into the tumour bed on the pelvic wall. The brachytherapy is carried out postoperatively. An accurate analysis cannot be done because of the short follow up and the few cases. The authors do believe that the survival results of this poor prognostic group may improve by means of this method after proper selection of patients.
C1 [Patyanik, Mihaly] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai Kozpont, Uzsoki u. 29., H-1145 Budapest, Hungary.
[Mayer, Arpad] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai Kozpont, Uzsoki u. 29., H-1145 Budapest, Hungary.
[Ungar, Laszlo] Szent Istvan Hospital, Department of Obstetrics and GynecologyBudapest, Hungary.
[Polgar, Istvan] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai Kozpont, Uzsoki u. 29., H-1145 Budapest, Hungary.
RP Patyanik, M (reprint author), Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai Kozpont, H-1145 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 171
EP 173
PG 3
ER
PT J
AU Totth,
Schnur, J
Ladanyi, A
Kopper, L
AF Totth, Arpad
Schnur, Janos
Ladanyi, Andrea
Kopper, Laszlo
TI Intracerebral Human Lymphoma - An Experimental Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lymphoma; CNS; tumor-model
ID lymphoma; CNS; tumor-model
AB Primary central nervous system lymphomas are rather rare, however, their frequency seems to be increasing in both high risk and immunocompetent patients with very poor prognosis. Here we describe a model intracerebrally xenotransplating human non Hodgkin lymphoma cells of B cell origin (HT 58). This offers a unique possibility to study the theraputic response, especially on systemic treatment. Briefly, one million lymphoma cells grew as meningeal tumor mass, infiltrating the brain directly as well as via the perivascular space. The lymphoma cells preserved all the phenotypic characteristics of the source tumor.
C1 [Totth, Arpad] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Schnur, Janos] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Ladanyi, Andrea] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 174
EP 176
PG 3
ER
PT J
AU Bergter, W
Fetzer, IC
Sattler, B
Ramadori, G
AF Bergter, Wolfgang
Fetzer, Ingrid-Corina
Sattler, Burkhardt
Ramadori, Giuliano
TI Granulomatous Hepatitis preceding Hodgkin's Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE granuloma; granulomatous hepatitis; Hodgkin's disease
ID granuloma; granulomatous hepatitis; Hodgkin's disease
AB Granulomas are a frequent finding in various organs with a wide range of causes. Hepatic granulomas most often occur in the course of sarcoidosis or tuberculosis. However, they also may develop during Hodgkin's disease or sometimes even precede lymphoma as shown in the case of a patient presented here. Early diagnosis of Hodgkin's disease is essential, and in the case of unexplained granulomatous hepatitis it can be achieved by taking the patients history into consideration.
C1 [Bergter, Wolfgang] Abteilung Gastroenterologie und Endokrinologie, Zentrum Innere Medizin, Robert Koch Str 40, 37075 Gottingen, Germany.
[Fetzer, Ingrid-Corina] Abteilung Gastroenterologie und Endokrinologie, Zentrum Innere Medizin, Robert Koch Str 40, 37075 Gottingen, Germany.
[Sattler, Burkhardt] Georg-August-University, Department of PathologyGottingen, Germany.
[Ramadori, Giuliano] Abteilung Gastroenterologie und Endokrinologie, Zentrum Innere Medizin, Robert Koch Str 40, 37075 Gottingen, Germany.
RP Ramadori, G (reprint author), Abteilung Gastroenterologie und Endokrinologie, Zentrum Innere Medizin, 37075 Gottingen, Germany.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 177
EP 180
PG 4
ER
PT J
AU Kovacs, J
Poka, R
AF Kovacs, Judit
Poka, Robert
TI Lipoma of the Uterus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE uterine neoplasm; postmenopausal woman; lipoma; immunohistochemistry
ID uterine neoplasm; postmenopausal woman; lipoma; immunohistochemistry
AB Lipoma of the uterus is a rare condition usually developing in postmenopausal women. Clinical symptoms and physical signs are similar to those found in leiomyomas. The histiogenesis of these lesions is still unclear. We report a case of a pure intramural lipoma of the uterus illustrating characteristic morphological and histological findings. Additional immunohistochemical studies underline the lipomatous but not leiomyomatous nature of the tumor.
C1 [Kovacs, Judit] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
[Poka, Robert] University Medical School of Debrecen, Department of Gynecology and ObstetricsDebrecen, Hungary.
RP Kovacs, J (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 181
EP 183
PG 3
ER
PT J
AU Kohalmi, F
Strausz, J
Egervary, M
Szekeres, Gy
Timar, J
AF Kohalmi, Ferenc
Strausz, Janos
Egervary, Marta
Szekeres, Gyorgy
Timar, Jozsef
TI Differential Expression of Markers in Extensive and Restricted Langerhans Cell Histiocytosis (LCH)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Langerhans cell histiocytosis; restricted and extensive variants; markers; immunohistochemistry
ID Langerhans cell histiocytosis; restricted and extensive variants; markers; immunohistochemistry
AB Langerhans cell histiocytosis (LCH) represents a poorly defined pathologic entity characterized by diverse clinical appearence and falling into two major categories namely a restricted and an extensive disease. Since the outcome and the course of the disease is variable, we postulated that this might be reflected by the phenotype of the Langerhans cells. We have selected 11 adult restricted cases and 10 extensive childhood cases and compared the phenotype of LCH cells by immunohistochemistry on paraffin sections. Morphometric analysis indicated a significantly higher expression of histiocytic (CD68, S-100, lysozyme) markers in the adult restricted cases compared to the extensive form of the disease. Both groups were equally positive for LCH marker CD1a and negative for T cell marker CD4. On the other hand, HLA-DR expression was significantly higher in LCH cells of the extensive childhood cases suggesting higher activation. These data suggest that LCH cells have a different phenotype in the extensive childhood and restricted adult LCH where the latter is characterized by a more differentiated histiocytic phenotype.
C1 [Kohalmi, Ferenc] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Strausz, Janos] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Egervary, Marta] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Szekeres, Gyorgy] Laboratory of HistopathologyPecs-Cserkut, Hungary.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 184
EP 187
PG 4
ER
PT J
AU Honn, VK
Aref, A
Chen, QY
Cher, M
Crissman, DJ
Forman, DJ
Gao, X
Grignon, D
Hussain, M
Porter, TA
Pontes, E
Powell, I
Redman, B
Sakr, W
Severson, R
Tang, GD
Wood, PD
AF Honn, V Kenneth
Aref, Amer
Chen, Q Yong
Cher, Michael
Crissman, D John
Forman, D Jeffrey
Gao, Xiang
Grignon, David
Hussain, Maha
Porter, T Arthur
Pontes, J. Edson
Powell, Isaac
Redman, Bruce
Sakr, Wael
Severson, Richard
Tang, G Dean
Wood, P David
TI Prostate Cancer - Old Problems and New Approaches Part II.
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE prostate cancer; diagnosis; prognosis; pathology; biology
ID prostate cancer; diagnosis; prognosis; pathology; biology
AB Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).
C1 [Honn, V Kenneth] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Aref, Amer] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Chen, Q Yong] Wayne State University, Department of PathologyDetroit, USA.
[Cher, Michael] Wayne State University, Department of UrologyDetroit, USA.
[Crissman, D John] Wayne State University, Department of PathologyDetroit, USA.
[Forman, D Jeffrey] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Gao, Xiang] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Grignon, David] Wayne State University, Department of PathologyDetroit, USA.
[Hussain, Maha] Wayne State University, Department of MedicineDetroit, USA.
[Porter, T Arthur] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Pontes, J. Edson] Wayne State University, Department of UrologyDetroit, USA.
[Powell, Isaac] Wayne State University, Department of UrologyDetroit, USA.
[Redman, Bruce] Wayne State University, Department of MedicineDetroit, USA.
[Sakr, Wael] Wayne State University, Department of PathologyDetroit, USA.
[Severson, Richard] Wayne State University, Department of Family MedicineDetroit, USA.
[Tang, G Dean] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Wood, P David] Wayne State University, Department of UrologyDetroit, USA.
RP Honn, VK (reprint author), Wayne State University, Department of Radiation Oncology, 48202 Detroit, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1996
VL 2
IS 3
BP 191
EP 211
PG 21
ER
PT J
AU Buzas, IE
Mikecz, K
Glant, TT
AF Buzas, I Edit
Mikecz, Katalin
Glant, T Tibor
TI Aggrecan: A Target Molecule of Autoimmune Reactions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE proteoglycan; aggrecan; arthritis; spondylitis; autoimmune; cartilage
ID proteoglycan; aggrecan; arthritis; spondylitis; autoimmune; cartilage
AB Aggrecan in cartilage forms aggregates with hyaluronan and link protein, embedded in a collagen network. It accounts for the compressive stiffness and resilience of the hyaline cartilage. Many forms of inflammatory arthritis were shown to be accompanied with aggrecan degradation and loss from the cartilage. The loss of this major component of cartilage renders the tissue more vulnerable when exposed to abrasive forces. Therefore, aggrecan degradation may significantly contribute to cartilage destruction in arthritis. Furthermore, fragments of degraded aggrecan are released during joint inflammation. Thus, molecules of an avascular, immune-privileged tissue (hyaline cartilage) may become accessible to the cells of the immune system. Similarly, there is a ''leakage'' of aggrecan fragments from cartilage during aging and after joint injury, which may also lead to autosensibilisation. Autoimmune reactivity to aggrecan can be detected in human joint diseases, as well as in animal models of arthritis. The epitopes involved in these processes are currently being identified. Recent data from work with mice suggest a strong immune response focused to the N-terminal G1 domain of aggrecan that leads to arthritis and spondylitis.
C1 [Buzas, I Edit] University of Medicine, The Institute of Anatomy, Histology and Embryology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Mikecz, Katalin] Rush Medical University at Rush-Presbyterian-St. Luke's Medical Center, Department of BiochemistryChicago, USA.
[Glant, T Tibor] Rush Medical University at Rush-Presbyterian-St. Luke's Medical Center, Department of BiochemistryChicago, USA.
RP Buzas, IE (reprint author), University of Medicine, The Institute of Anatomy, Histology and Embryology, H-4012 Debrecen, Hungary.
EM edit@chondron.anat.dote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 219
EP 228
PG 10
ER
PT J
AU Folberg, R
Fleck, M
Mehaffey, GM
Meyer, M
Bentler, ES
Woolson, FR
Pe'er, J
AF Folberg, Robert
Fleck, Margaret
Mehaffey, G Mary
Meyer, Margaret
Bentler, E Suzanne
Woolson, F Robert
Pe'er, Jacob
TI Mapping the Location of Prognostically Significant Microcirculatory Patterns in Ciliary Body and Choroidal Melanomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE melanoma; metastasis; prognosis; angiogenesis; vascularity; image analysis
ID melanoma; metastasis; prognosis; angiogenesis; vascularity; image analysis
AB The microcirculation of choroidal and ciliary body melanomas is remodeled into architecturally distinctive patterns. The presence of two histologic microvascular patterns, networks and parallel vessels with cross-linking, is strongly associated with metastasis. This study was designed to test the hypothesis that networks and parallel vessels with cross-linking patterns are not distributed evenly throughout the tumor. From a set of 234 eyes removed for ciliary body or choroidal melanoma, 152 tumors contained at least one focus of either vascular networks or parallel vessels with cross-linking. Histological cross-sections were digitized and foci of tumor containing these patterns were pseudocolorized so that their location within the periphery or central tumor zone could be mapped. Ciliary body and choroidal melanomas vary widely in size and shape and it is not appropriate to describe the periphery of a tumor as a fixed value because in a small tumor, the periphery thus defined would occupy a larger percent area than in a larger tumor. In this study, the peripheral and central zones of each tumor were described by a function that was constant from tumor to tumor, allowing the width of the peripheral and central zones to vary proportionally with tumor size. Observed counts of vascular patterns per zone were compared statistically with expected counts based upon the percent area occupied by the peripheral and central zones. Discrete foci of networks and parallel with cross-linking vessels are over-represented in the tumor periphery (p < 0.0001).
C1 [Folberg, Robert] University of Iowa, Department of Ophthalmology, 100 Medical Research Center, Room 233, 52242-1182 Iowa City, IA, USA.
[Fleck, Margaret] University of Iowa, Department of Computer ScienceIowa City, USA.
[Mehaffey, G Mary] University of Iowa, Department of Ophthalmology, 100 Medical Research Center, Room 233, 52242-1182 Iowa City, IA, USA.
[Meyer, Margaret] University of Iowa, Department of Ophthalmology, 100 Medical Research Center, Room 233, 52242-1182 Iowa City, IA, USA.
[Bentler, E Suzanne] University of Iowa, Department of Preventive MedicineIowa City, USA.
[Woolson, F Robert] University of Iowa, Department of Preventive MedicineIowa City, USA.
[Pe'er, Jacob] Hadassah-Hebrew University, Department of OphthalmologyJerusalem, Israel.
RP Folberg, R (reprint author), University of Iowa, Department of Ophthalmology, 52242-1182 Iowa City, USA.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 229
EP 236
PG 8
ER
PT J
AU Berczi, L
Tamassy, K
Fekete, B
Kopper, L
AF Berczi, Lajos
Tamassy, Klara
Fekete, Bela
Kopper, Laszlo
TI Eosinophils and Mast Cells in Helicobacter Pylori Infected Gastric Mucosa
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE eosinophilia; gastritis; Helicobacter pylori
ID eosinophilia; gastritis; Helicobacter pylori
AB Although Helicobacter pylori (HP) is frequently associated with chronic active gastritis and peptic ulcers, its exact pathogenic role or the pathomechanism is still unclear. Here, we describe a striking, statistically significant increase of eosinophils in HP infected gastric mucosa compared to HP negative gastritis with similar activity. In both cases, the mean number of the mast cells in the mucosa was comparable, although the individual values showed wide distribution. The source and role of eosinophilia in HP infected mucosa, the potential link between the degree of eosinophilia and the clinical progression, as well as between eosinophils and mast cells require further study.
C1 [Berczi, Lajos] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Tamassy, Klara] Semmelweis University of Medicine, Teaching HospitalBudapest, Hungary.
[Fekete, Bela] Semmelweis University of Medicine, Teaching HospitalBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Berczi, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM berczi@korb1.sote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 237
EP 238
PG 2
ER
PT J
AU Szende, B
Lubben, Th
Romics, I
Vass, L
AF Szende, Bela
Lubben, Thomas
Romics, Imre
Vass, Laszlo
TI Apoptosis in Untreated and Hormone-Treated Prostate Cancer of Various Histological Types
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; prostate cancer; hormone therapy
ID apoptosis; prostate cancer; hormone therapy
AB A total of 102 (66 untreated and 36 hormone-treated) prostate cancers were examined histologically in order to determine their histological grade and the percentage of apoptotic tumor cells. The less differentiated the tumors were, the higher the spontaneous apoptotic activity was. Hormone therapy increased the apoptotic index in the prostate cancers. The increase was of greater significance in grade I than in grade II and grade III tumors. The therapeutic consequences of these findings and the possibility of different oncogene-expressions in various histological types of prostate cancer are discussed.
C1 [Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Lubben, Thomas] National Institute for Rheumatology and PhysiotherapyBudapest, Hungary.
[Romics, Imre] National Institute for Rheumatology and PhysiotherapyBudapest, Hungary.
[Vass, Laszlo] Flor Ferenc University Hospital of Pest CountyKistarcsa, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 239
EP 241
PG 3
ER
PT J
AU Horvath, JA
Szabo, A
Gaspar, T
Bognar, L
Tekeres, M
AF Horvath, J Attila
Szabo, Anita
Gaspar, Tunde
Bognar, Lajos
Tekeres, Miklos
TI M-ESLON (retard release morphine sulphate capsules) for Pain Control in Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer pain; morphine sulphate; controlled release; side effects
ID cancer pain; morphine sulphate; controlled release; side effects
AB The pain of patients who were in the terminal phase of advanced malignant tumors was successfully relieved by M-ESLON capsules of controlled release morphine sulphate (10-30-60-100 mg). The most frequent side effects (sickness, vomiting, obstipation) were effectively controlled. The concentration of the drug in the plasma was stable, therefore the lasting pain relief was ensured.
C1 [Horvath, J Attila] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, 13 Ifjusag Rd., H-7643 Pecs, Hungary.
[Szabo, Anita] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, 13 Ifjusag Rd., H-7643 Pecs, Hungary.
[Gaspar, Tunde] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, 13 Ifjusag Rd., H-7643 Pecs, Hungary.
[Bognar, Lajos] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, 13 Ifjusag Rd., H-7643 Pecs, Hungary.
[Tekeres, Miklos] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, 13 Ifjusag Rd., H-7643 Pecs, Hungary.
RP Horvath, JA (reprint author), University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, H-7643 Pecs, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 242
EP 243
PG 2
ER
PT J
AU Orosz, Zs
Kelemen, J
Szentirmay, Z
AF Orosz, Zsolt
Kelemen, Janos
Szentirmay, Zoltan
TI Granular Cell Variant of Atypical Fibroxanthoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE fibrohistiocytic tumors; granular cells; atypical fibroxanthoma
ID fibrohistiocytic tumors; granular cells; atypical fibroxanthoma
AB We report a case of atypical fibroxanthoma of the ear in which the dominant part of the tumor has granular cell appearance. Areas identical to conventional atypical fibroxanthoma were present only at the lateral infiltrating borders. Histologically the granular cells resembled those of the classical granular cell tumors but exhibited significant pleomorphism and a high mitotic rate. Immunostains for vimentin, CD68 and NK1/C3 were positive but for S-100, HMB-45, myogenic and epithelial markers were negative. The predominance of the granular cells in an atypical fibroxanthoma supports the concept that a small subset of tumors with granular cell phenotype are of nonneural origin.
C1 [Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Kelemen, Janos] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Szentirmay, Zoltan] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
RP Orosz, Zs (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 244
EP 247
PG 4
ER
PT J
AU Sinkovics, GJ
AF Sinkovics, G Joseph
TI Contradictory Concepts in the Etiology and Regression of Kaposi's Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Growth factor cascade; human herpesvirus 8; apoptosis; protooncogenes-oncogenes; retro-lentiviruses
ID Growth factor cascade; human herpesvirus 8; apoptosis; protooncogenes-oncogenes; retro-lentiviruses
AB The Introduction is an overview of 3 decades of works performed by Professor Ferenc Gyorkey? (in many cases in collaboration with the author) and aimed at the elucidation of viral participation in the etiology of arteriosclerosis, SLE, hairy cell leukemia, HD, AIDS and KS. Controversial issues surrounding the etiology, treatment and regression of KS are discussed in terms of paracrine and autocrine loops of growth factors; protooncogene-oncogene activations, immunosuppression and retro- and/or herpesviral etiology. In regressing KS lesions the roles played by Fas, Bcl-2, Bax, TNFß; apoptotic-antiapoptotic events; and antiangiogenesis agents especially that of Hu-r-IFNa are elaborated on.
C1 [Sinkovics, G Joseph] St. Joseph's Hospital, Cancer Institute, 3001 W. MLK Jr. Blvd., 33607 Tampa, Florida, USA.
RP Sinkovics, GJ (reprint author), St. Joseph's Hospital, Cancer Institute, 33607 Tampa, USA.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 249
EP 267
PG 19
ER
PT J
AU Nagy, K
Barabas,
Varkonyi, V
Horvath, A
AF Nagy, Karoly
Barabas, Eva
Varkonyi, Viktoria
Horvath, Attila
TI Determination of HIV-1 Subtypes in Hungary by Synthetic Peptides Representing the V3 Loop of env
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV-1; subtypes; Hungary
ID HIV-1; subtypes; Hungary
AB For the determination of HIV-1 diversity and serotyping of HIV-1 subtypes, an enzyme immunoassay was developed based on synthetic peptides representing immunodominant epitopes of the V3 loop of HIV-1 subtypes A, B, C and E, respectively. Sera from 53 asymptomatic HIV-1 infected individuals were tested for their pattern of binding reactivity to the synthetic peptides. 45/52 (85%) of the sera reacted exclusively to V3 peptide representing HIV-1 B subtypes, 4/52 (7.6%) of the sera showed cross reacticity to A/B peptides and 1/52 (1.9%) of the sera reacted with both A and C peptides. No single reactivity with subtype A or E peptides have been observed. Results together with nucleotide sequence analysis of the V3 region of clinical isolates suggest that HIV-1 infection in Hungary has been induced predominantly by strains belonging to HIV-1 subtype B.
C1 [Nagy, Karoly] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Barabas, Eva] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Varkonyi, Viktoria] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Horvath, Attila] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
RP Nagy, K (reprint author), National Institute for Dermato-Venereology, H-1085 Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 268
EP 271
PG 4
ER
PT J
AU Fife, K
Bower, M
AF Fife, Kathryn
Bower, Mark
TI Current Management of AIDS Related Non Hodgkin's Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE AIDS; Non-Hodgkin's lymphoma
ID AIDS; Non-Hodgkin's lymphoma
AB Non Hodgkin's lymphoma is the AIDS defining illness in 3-3.5% of patients and is increasing in incidence as the survival of HIV infected people improves. The incidence of these intermediate/high grade B cell malignancies is sixty times higher than in the general population. The most important prognostic factors are a CD4 positive lymphocyte count of <100 cells/mm3, a prior AIDS defining diagnosis, an ECOG performance status >2 and primary cerebral origin. Patients with any of these factors are most likely to benefit from palliative rather than radical treatment. Good prognosis patients have a 30-40% chance of cure from their lymphoma with carefully administered intensive chemotherapy.
C1 [Fife, Kathryn] Charing Cross Hospital, Medical Oncology Unit, Fulham Palace Road, W6 8RF London, UK.
[Bower, Mark] Charing Cross Hospital, Medical Oncology Unit, Fulham Palace Road, W6 8RF London, UK.
RP Fife, K (reprint author), Charing Cross Hospital, Medical Oncology Unit, W6 8RF London, UK.
EM m.bower@cxwms.ac.uk
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 272
EP 275
PG 4
ER
PT J
AU Honn, VK
Aref, A
Chen, QY
Cher, LM
Crissman, DJ
Forman, DJ
Gao, X
Grignon, D
Hussain, M
Porter, TA
Pontes, E
Powell, I
Redman, B
Sakr, W
Severson, R
Tang, GD
Wood, PD
AF Honn, V Kenneth
Aref, Amer
Chen, Q Yong
Cher, L Michael
Crissman, D John
Forman, D Jeffrey
Gao, Xiang
Grignon, David
Hussain, Maha
Porter, T Arthur
Pontes, J. Edson
Powell, Isaac
Redman, Bruce
Sakr, Wael
Severson, Richard
Tang, G Dean
Wood, P David
TI Prostate Cancer Old Problems and New Approaches Part III.
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE prostate cancer; prevention; radiotherapy; chemotherapy
ID prostate cancer; prevention; radiotherapy; chemotherapy
AB In Part Three of this review, we begin with an analysis of prevention strategies for prostate cancer followed by a discussion of the clinical use of molecular techniques for the evaluation and treatment of patients with clinically localized prostate cancer. New developments in neutron and photon therapy of prostate cancer are addressed as well as the use of systemic radiotherapy for the treatment of bone metastases. Finally, we conclude with the role of hormonal therapy in the treatment of prostate cancer and the current status of development of chemo therapeutic regimens for the treatment of prostate cancer.
C1 [Honn, V Kenneth] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Aref, Amer] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Chen, Q Yong] Wayne State University, Department of PathologyDetroit, USA.
[Cher, L Michael] Wayne State University, Department of UrologyDetroit, USA.
[Crissman, D John] Wayne State University, Department of PathologyDetroit, USA.
[Forman, D Jeffrey] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Gao, Xiang] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Grignon, David] Wayne State University, Department of PathologyDetroit, USA.
[Hussain, Maha] Wayne State University, Department of MedicineDetroit, USA.
[Porter, T Arthur] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Pontes, J. Edson] Wayne State University, Department of UrologyDetroit, USA.
[Powell, Isaac] Wayne State University, Department of UrologyDetroit, USA.
[Redman, Bruce] Wayne State University, Department of MedicineDetroit, USA.
[Sakr, Wael] Wayne State University, Department of PathologyDetroit, USA.
[Severson, Richard] Wayne State University, Department of Family MedicineDetroit, USA.
[Tang, G Dean] Wayne State University, Department of Radiation Oncology, 431 Chemistry, 48202 Detroit, MI, USA.
[Wood, P David] Wayne State University, Department of UrologyDetroit, USA.
RP Honn, VK (reprint author), Wayne State University, Department of Radiation Oncology, 48202 Detroit, USA.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1996
VL 2
IS 4
BP 276
EP 292
PG 17
ER
PT J
AU Schwab, M
AF Schwab, Manfred
TI MYCN Amplification in Neuroblastoma: a Paradigm for the Clinical Use of an Oncogene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE neuroblastoma; N-Myc; prediction; therapy
ID neuroblastoma; N-Myc; prediction; therapy
AB Increase of the dosage of cellular oncogenes by DNA amplification is a frequent genetic alteration of cancer cells. The presence of amplified cellular oncogenes is usually signalled by conspicuous chromosomal abnormalities, ''double minutes'' (DMs) or ''homogeneously staining chromsomal regions'' (HSRs). Some human cancers carry a specific amplified oncogene at high incidence. In neuroblastomas the amplification of MYCN has been found associated with aggressively growing cancers and is an indicator for poor prognosis. MYCN amplification is of predictive value for identifying neuroblastoma patiens that require specific therapeutic regimens and for identifying patients that will not benefit from chemotherapy.
C1 [Schwab, Manfred] German Cancer Research Center, Division of Cytogenetics, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
RP Schwab, M (reprint author), German Cancer Research Center, Division of Cytogenetics, D-69120 Heidelberg, Germany.
EM m.schwab@dkfz-heidelberg.de
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 3
EP 7
PG 5
ER
PT J
AU Uusitalo, M
Kivela, T
AF Uusitalo, Marita
Kivela, Tero
TI The HNK-1 Carbohydrate Epitope and the Human Eye in Health and Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cell adhesion; Ciliary body; Inner connective tissue layer; Natural killer cell; Retina; Subepithelial matrix cell
ID Cell adhesion; Ciliary body; Inner connective tissue layer; Natural killer cell; Retina; Subepithelial matrix cell
AB The HNK-1 carbohydrate epitope is part of many cell membrane and extracellular matrix molecules, several of which have been implicated in cell adhesion. It is a versatile tool in eye research. In the human eye this epitope is present in the retina, the optic and ciliary nerves, the ciliary and iris epithelia, the zonular lamella, and the sclera. It is phylogenetically conserved, but the positive cell types vary from species to species. In addition to revealing interspecies differences in the vertebrate retina, the HNK-1 epitope has been used to identify a novel cell type in the eye: the subepithelial matrix cells that reside in the inner connective tissue layer (ICTL) of the ciliary body. Although these cells resemble fibroblasts in ultrastructure, they form a distinct cell population that differs in antigenic profile from fibroblasts in other tissues. The HNK-1 epitope is also associated with the elastic fiber system of the ICTL, which may be produced by the subepithelial matrix cells. It may help to structurally stabilize the ciliary body and the retina. The HNK-1 epitope is also involved in many important eye diseases. The subepithelial matrix cells seem to be susceptible to irrreversible atrophy as a result of glaucoma, thermal injury, and tissue compression. On the other hand, the HNK-1 epitope is found in the extracellular matrix of secondary cataracts and may contribute to its pathogenesis. Finally, this epitope has proved to be useful in identifying deposits of exfoliation material, and in tracing neuroepithelial derivatives in developmental anomalies and tumors of the eye.
C1 [Uusitalo, Marita] Helsinki University Central Hospital, Department of Ophthalmology, Haartmaninkatu 4C, FIN-00290 Helsinki, Finland.
[Kivela, Tero] Helsinki University Central Hospital, Department of Ophthalmology, Haartmaninkatu 4C, FIN-00290 Helsinki, Finland.
RP Uusitalo, M (reprint author), Helsinki University Central Hospital, Department of Ophthalmology, FIN-00290 Helsinki, Finland.
EM msuusita@cc.helsinki.fi
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 8
EP 14
PG 7
ER
PT J
AU Papai, Zs
Feja, NCh
Eid, H
Sztan, M
Olah, E
Szendroi, M
AF Papai, Zsuzsa
Feja, N Christina
Eid, Hanna
Sztan, Mariann
Olah, Edit
Szendroi, Miklos
TI P53 Overexpression as an Indicator of Overall Survival and Response to Treatment in Osteosarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE osteosarcoma; p53 overexpression
ID osteosarcoma; p53 overexpression
AB The p53 gene located at chromosome 17p13 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twenty-one patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-responders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.
C1 [Papai, Zsuzsa] National Institute of Oncology, Rath Gyorgy ut 7., H-1525 Budapest, Hungary.
[Feja, N Christina] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Eid, Hanna] National Institute of Oncology, Rath Gyorgy ut 7., H-1525 Budapest, Hungary.
[Sztan, Mariann] National Institute of Oncology, Rath Gyorgy ut 7., H-1525 Budapest, Hungary.
[Olah, Edit] National Institute of Oncology, Rath Gyorgy ut 7., H-1525 Budapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
RP Papai, Zs (reprint author), National Institute of Oncology, H-1525 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 15
EP 19
PG 5
ER
PT J
AU Benedeczky, I
Nemcsok, J
AF Benedeczky, Istvan
Nemcsok, Janos
TI Giant Mitochondria as Possible Bioindicators of Environmental Injuries in Fish Liver
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE giant mitochondria; fish liver; herbicide (paraquat); electron microscopic cytopathology
ID giant mitochondria; fish liver; herbicide (paraquat); electron microscopic cytopathology
AB The effect of hypoxia (80 pHg) and simultaneously applied paraquat (1,1'-dimethyl-4,4-bipyridynum dichloride) was investigated on carp liver using electron microscopic methods. The appearance of giant mitochondria was the most conspicuous alteration in the liver cells. Most of the giant mitochondria were elongated and rod-shaped, often arranged side by side forming clusters beside the nucleus. Crook-like and irregular forms also occured among giant mitochondria. The lenght of the giant mitochondria often was greater than the diameter of nucleus: namely 5-10 µm. The outer membrane of the giant mitochondria was well preserved, but inner membranes (cristae) were usually absent, and a high density matrix filled in the inner space of mitochondria. High power magnification often revealed a regular, filamentous paracristal arrangement in the dense material of the matrix. Swollen giant mitochondria with light matrix and tubular elements also occured in low number. Although fine structural characteristics of carp liver giant mitochondria are not specific for inducing agents (hypoxia + paraquat treatment) the appearance of altered giant mitochondria may be a useful signal for monitoring cell damaging enviromental xenobiotics.
C1 [Benedeczky, Istvan] Attila Jozsef University, Department of BiochemistrySzeged, Hungary.
[Nemcsok, Janos] Attila Jozsef University, Department of BiochemistrySzeged, Hungary.
RP Benedeczky, I (reprint author), Attila Jozsef University, Department of Biochemistry, Szeged, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 20
EP 25
PG 6
ER
PT J
AU Polanec, J
Patzer, J
Grzybowski, J
Strukelj, M
Pavelic, PZ
AF Polanec, Janja
Patzer, Jan
Grzybowski, Jacek
Strukelj, Milan
Pavelic, P Zlatko
TI Amount and Avidity of IgG Antibodies to Pseudomonas Aeruginosa Exotoxin A Antigen in Cystic Fibrosis Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ELISA; avidity; cystic fibrosis; exotoxin A; Pseudomonas aeruginosa
ID ELISA; avidity; cystic fibrosis; exotoxin A; Pseudomonas aeruginosa
AB Amount and avidity of serum IgG antibodies to Pseudomonas aeruginosa exotoxin A in sera of 31 patients with cystic fibrosis (CF) was studied. Eight patients had P. aeruginosa isolated from the sputum on multiple occasions, while from 23 patients no P. aeruginosa was isolated. Amount of IgG antibodies to P. aeruginosa exotoxin A were significantly increased in the serum of patients with P. aeruginosa pulmonary colonization (p<0.0001). On the contrary, serum IgG avidity in the colonized and in the non-colonized CF patients was low (<10) and was statistically different when compared to the 30 age-matched healthy controls (p<0.0001). There was no change in IgG avidity in six chronically infected CF patients from whom we obtained serum samples after half a year period (p=0,55).
C1 [Polanec, Janja] Institute of MicrobiologyLjubljana, Slovenia.
[Patzer, Jan] Children's Memorial HospitalWarsaw, Poland.
[Grzybowski, Jacek] Military Institute of MedicineWarsaw, Poland.
[Strukelj, Milan] Pediatric ClinicLjubljana, Slovenia.
[Pavelic, P Zlatko] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, Ohio, USA.
RP Pavelic, PZ (reprint author), University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, 45267-0528 Cincinnati, USA.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 26
EP 29
PG 4
ER
PT J
AU Polanec, J
Pavelic, PZ
Krizman, I
Osredkar, J
AF Polanec, Janja
Pavelic, P Zlatko
Krizman, Igor
Osredkar, Joe
TI Low Serum Pancreatitis-Associated Protein Does not Exclude Complications in Mild Acute Pancreatitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pancreatitis-associated protein; ELISA; acute pancreatitis
ID pancreatitis-associated protein; ELISA; acute pancreatitis
AB Normal serum PAP levels on admission to the hospital in patiens with acute pancreatitis has been proposed to help select the patients who are not going to develop complications. The aims of this study were, first, to assess the specificity of serum pancreatitis - associated protein (PAP) serology test and second, to evalute the usefulness of the test for prediciting complications in acute pancreatitis on admission to the hospital. The sensitivity of the PAP ELISA in patiens with acute pancreatitis on admission to the hospital was 70% and the serum PAP levels significantly higher than in healthy controls (p < 0.0001). However, the serum PAP levels in patients with acute pancreatitis were not significantly different from values in patients with various abdominal diseases (p < 0.58). Serum PAP levels gave good correlation to APACHE II (p = 0.02) and CRP (p = 0.01). Two patients with local complications (necrotizing pancreatitis, pancreatic fluid collection) had elevated serum PAP levels on admission to the hospital (> 100 ng/ml). The diagnostic specififity of PAP ELISA is low. Patients, who develop local complications in acute pancreatitis can not be excluded by normal serum PAP levels on admission to the hospital.
C1 [Polanec, Janja] Institute for Clinical Chemistry and BiochemistryLjubljana, Slovenia.
[Pavelic, P Zlatko] University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck SurgeryCincinnati, USA.
[Krizman, Igor] Gastroenterology Clinic, Japljeva 2, 1000 Ljubljana, Slovenia.
[Osredkar, Joe] Institute for Clinical Chemistry and BiochemistryLjubljana, Slovenia.
RP Krizman, I (reprint author), Gastroenterology Clinic, 1000 Ljubljana, Slovenia.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 30
EP 33
PG 4
ER
PT J
AU Grinevich, AJ
Beres, J
Bendyug, DG
AF Grinevich, Akimovich Jurij
Beres, Jozsef
Bendyug, Dmitrijevna Galina
TI A Trace Element Preparation Increases Antitumor Activity in Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE trace elements; antimetastatic; immunomodulation
ID trace elements; antimetastatic; immunomodulation
AB A trace element preparation (Beres Drops Plus, BDP) produced immunomodulatory effects in previous in vitro and in vivo experiments. Here, C57B1/6 inbred mice were transplanted with either Lewis lung tumor or with B16 melanoma. BDP was given intraperitoneally a. before transplantation; b. after transplantation or c. after the removal of the primary tumor. As a result, BDP pretreatment could slow down the tumor progression by decreasing the number and the volume of metastases as well as the proportion of mice with metastases without influencing the growth of the primary tumors. Furthermore, BDP treatment improved the immunological activity of the tumor-bearing host, too. These preliminary data suggest that the parenteral administration of the practically non-toxic BDP could help to control tumor progression in experimental models.
C1 [Grinevich, Akimovich Jurij] Ministry of Health of Ukraine, Ukrainian Research Institute of Oncology and Radiology, 33/43 Lomonosov St, 252022 Kiev, Ukraine.
[Beres, Jozsef] Beres Co. Ltd., Department of Research and DevelopmentBudapest, Hungary.
[Bendyug, Dmitrijevna Galina] Ministry of Health of Ukraine, Ukrainian Research Institute of Oncology and Radiology, 33/43 Lomonosov St, 252022 Kiev, Ukraine.
RP Grinevich, AJ (reprint author), Ministry of Health of Ukraine, Ukrainian Research Institute of Oncology and Radiology, 252022 Kiev, Ukraine.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 34
EP 37
PG 4
ER
PT J
AU Uleckiene, S
Giciute, L
AF Uleckiene, Saule
Giciute, Laima
TI Carcinogenicity of Sulfuric Acid in Rats and Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sulfuric acid; carcinogenicity; rats; mice
ID sulfuric acid; carcinogenicity; rats; mice
AB An International Agency for Research on Cancer (IARC) committee recognized aerosol of sulphuric acid as a human carcinogen on the basis of epidemiological studies. No experimental studies on the carcinogenicity, either of sulfuric acid aerosol or of sulfuric acid itself was available. Our aim was to determine whether sulfuric acid is a causal or modifying factor in carcinogenesis, especially in the respiratory tract. We used two species of laboratory animals (both sexes) - 315 Wistar rats and 219 CBAxC57Bl mice in a long term experimental study. The rats were treated with sulfuric acid (maximal tolerated doses, by chronic intratracheal instillations or by gastric intubations) and/or benzo(a)pyrene (by intratracheal instillations). The mice were treated with sulfuric acid (by chronic gastric intubations) and/or urethane (by intraperitoneal injections). We observed the animals throughout their lives and performed gross and microscopic examination of all organs. The results of the first year of study did not provide clear evidence either for sulfuric acid carcinogenicity or for co-carcinogenicity. However, in the second year tumors appeared in those organs where sulfuric acid acted directly. A modifying (stimulating) effect of sulfuric acid on carcinogenesis induced with benzo(a)pyren was observed in rats. Sulfuric acid did not influence lung carcinogenesis induced with urethane in mice.
C1 [Uleckiene, Saule] Lithuanian Oncology Center, Santariskiu 1., 2600 Vilnius, Lithuania.
[Giciute, Laima] Lithuanian Oncology Center, Santariskiu 1., 2600 Vilnius, Lithuania.
RP Uleckiene, S (reprint author), Lithuanian Oncology Center, 2600 Vilnius, Lithuania.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 38
EP 43
PG 6
ER
PT J
AU Kovesi, Gy
Paloczi, K
Onody, K
Fekete, B
AF Kovesi, Gyorgy
Paloczi, Katalin
Onody, Klara
Fekete, Bela
TI Immunologic Profile of Patients Suffering from Herpes Simplex Virus (HSV) -Associated Oral Lesions Treated with Natural Human Interferon Alpha (Egiferon)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE interferon alpha; herpes virus; lymphocyte subpopulations
ID interferon alpha; herpes virus; lymphocyte subpopulations
AB 10 consecutive patients with HSV-associated chronic oral lesions were treated with Egiferon for ten days. There were a statistically significant increase in the Large Granule Lymphocyte (LGL) counts and the number of spontaneous E rosette forming cells by the end of the treatment period. Interferon alpha brought about a preferential expression of CD8, CD11b, CD14, CD25 and CD45RO cell surface molecules without any effect on the expression of CD2, CD3, CD4, CD20 and HLA-DR.
C1 [Kovesi, Gyorgy] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Paloczi, Katalin] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Onody, Klara] EGIS Pharmaceuticals PLCBudapest, Hungary.
[Fekete, Bela] Semmelweis University of Medicine, Teaching Hospital, Kutvolgyi ut 4., 1125 Budapest, Hungary.
RP Fekete, B (reprint author), Semmelweis University of Medicine, Teaching Hospital, 1125 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 44
EP 46
PG 3
ER
PT J
AU Kiss, F
Salamon, F
Rozsahegyi, J
AF Kiss, Ferenc
Salamon, Ferenc
Rozsahegyi, Jozsef
TI Changing Pattern of Bladder Cancer Cytology (Haynal Imre University Experience)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE urinary cytology; sensitivity; transitional cell neoplasms
ID urinary cytology; sensitivity; transitional cell neoplasms
AB Urinary cytology reports of 151 patients with histologically verified tumors from the periods 1981-1985 and 1991-1995 were analyzed. No significant change in the overall sensitivity of tumor detection (76% and 76.8%, respectively) was found. In the group of well-differentiated (G0-G1) tumors, however, 60% of the more recent cases were cytologically positive or suspicious, 23% more than ten years ago. A decrease in the detection rate of G2 tumors in the last period (72% versus 89%) was probably caused by false negative reports due to frequent inflammatory changes in the specimens. Poorly differentiated (G3-G4) transitional cell tumors resulted in a high rate of positive cytological diagnoses (93% in both periods). In cases with negative cytology at clinical suspicion of tumor, repeated sampling increased the detection rate of G0-G1 lesions from 53% up to 60%. Optimal sampling and preparation technique, cytopathologists training and improved follow-up of patients are preconditions of sensitive and specific urinary cytology.
C1 [Kiss, Ferenc] Haynal Imre University of Health Sciences, Institute of Pathology, 2nd Institute of Pathology, Ulloi ut 93.Budapest, Hungary.
[Salamon, Ferenc] Haynal Imre University of Health Sciences, Institute of Pathology, 2nd Institute of Pathology, Ulloi ut 93.Budapest, Hungary.
[Rozsahegyi, Jozsef] Haynal Imre University of Health Sciences, Department of UrologyBudapest, Hungary.
RP Kiss, F (reprint author), Haynal Imre University of Health Sciences, Institute of Pathology, Budapest, Hungary.
EM kf@korb2.sote.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 47
EP 50
PG 4
ER
PT J
AU Kovalszky, I
Nagy, OJ
Gallai, M
Sebestyen, A
Schaff, Zs
Paku, S
Jeney, A
Iozzo, VR
AF Kovalszky, Ilona
Nagy, O Julia
Gallai, Monika
Sebestyen, Anna
Schaff, Zsuzsa
Paku, Sandor
Jeney, Andras
Iozzo, V Renato
TI Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE proteoglycan; biliary cirrhosis; decorin; perlecan; syndecan; GAG
ID proteoglycan; biliary cirrhosis; decorin; perlecan; syndecan; GAG
AB Proteoglycans play key roles in the physiological assembly of extracellular matrices and in the modulation of growth factor activities. During liver regeneration there is a profound remodelling of the connective tissue network with a concurrent alteration in proteoglycan gene expression. In the present study we have analyzed in detail the biochemical and molecular properties of the proteoglycans associated with biliary cirrhosis. The three major proteoglycans of human liver, namely decorin, syndecan and perlecan, were markedly elevated in the cirrhotic parenchyma as compared to normal liver tissue. Particularly elevated (eight fold) was the perlecan. This proteoglycan had not only heparan sulfate but also chondroitin and dermatan sulfate. Reverse transcriptase PCR revealed a marked enhancement of decorin and syndecan expression and detectable message for perlecan was found only in the cirrhotic liver. These results indicate that significant proteoglycan alterations are associated with the development of biliary cirrhosis and provide basis for future studies aimed at the characterization of the molecular events involved in the regulation of extracellular matrix deposition in this common human disease.
C1 [Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Nagy, O Julia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Gallai, Monika] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Iozzo, V Renato] Thomas Jefferson UniversityPhiladelphia, USA.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 51
EP 58
PG 8
ER
PT J
AU Bakos, N
Krasznai, G
Begany,
AF Bakos, Noemi
Krasznai, Geza
Begany, Agnes
TI Erythema Gyratum Repens an Immunological Paraneoplastic Dermatosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Erythema gyratum repens; Paraneoplastic dermatosis; Immunfluorescence
ID Erythema gyratum repens; Paraneoplastic dermatosis; Immunfluorescence
AB The authors present a patient with erythema gyratum repens who had a bronchogenic carcinoma. Autoantibodies and complement at the basement membrane zone of the skin was found which suggest that erythema gyratum repens may have an immunological pathogenesis but the nature of the antigen should be further characterised.
C1 [Bakos, Noemi] Hetenyi Geza Hospital, Department of Dermatology, Toszegi u. 21., 5000 Szolnok, Hungary.
[Krasznai, Geza] Hetenyi Geza County Hospital, Department of PathologySzolnok, Hungary.
[Begany, Agnes] University of Debrecen, Department of DermatologyDebrecen, Hungary.
RP Bakos, N (reprint author), Hetenyi Geza Hospital, Department of Dermatology, 5000 Szolnok, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 59
EP 61
PG 3
ER
PT J
AU Jassoy, Ch
Heinkelein, M
Sopper, S
AF Jassoy, Christian
Heinkelein, Martin
Sopper, Sieghart
TI The Role of the Envelope Glycoprotein in the Depletion of T Helper Cells in Human Immunodeficiency Virus Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; AIDS; envelope; T helper lymphocyte; pathogenesis; apoptosis
ID HIV; AIDS; envelope; T helper lymphocyte; pathogenesis; apoptosis
AB Infection with the human immunodeficiency virus (HIV) causes gradual depletion of CD4+ T helper lymphocytes and destruction of the lymphoid tissue, which ultimately leads to a fatal defect of the cellular immune system. Paramount to the understanding of the pathogenesis of HIV infection is to elucidate the mechanism which underlies the loss of T helper cells. Various ideas have been proposed in order to explain this issue. Several hypotheses have focused on the role of the envelope glycoprotein in this process. This review summarizes the data obtained and concepts proposed regarding the involvement of the HIV glycoprotein in the pathology of CD4+ T cell depletion.
C1 [Jassoy, Christian] Julius-Maximilians University, Institute for Virology and Immunobiology, Versbacher Strasse 7, D-97078 Wurzburg, Germany.
[Heinkelein, Martin] Julius-Maximilians University, Institute for Virology and Immunobiology, Versbacher Strasse 7, D-97078 Wurzburg, Germany.
[Sopper, Sieghart] Julius-Maximilians University, Institute for Virology and Immunobiology, Versbacher Strasse 7, D-97078 Wurzburg, Germany.
RP Jassoy, Ch (reprint author), Julius-Maximilians University, Institute for Virology and Immunobiology, D-97078 Wurzburg, Germany.
EM viro023@rzbox.uni-wuerzburg.de
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 62
EP 67
PG 6
ER
PT J
AU Barabas,
Falus, A
Nagy, K
Varkonyi, V
Temesvari, E
Horvath, A
AF Barabas, Eva
Falus, Andras
Nagy, Karoly
Varkonyi, Viktoria
Temesvari, Erzsebet
Horvath, Attila
TI The Dominant T-Helper Lymphocyte Function of HIV Infected Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; Th1; Th2; RT-PCR
ID HIV; Th1; Th2; RT-PCR
AB In HIV infection, the decrease in the number and functional activity of lymphocytes is accompanied by atopia and an increased level of total IgE and some specific IgE antibodies. This could be explained by the Th2 dominance induced by HIV replication and so a Th1-Th2 switch could have prognostic value. We investigated the characteristic T-helper phenotype dominance and its relationship to cytokine expression and IgE immune response in the early stage of asymptomatic HIV infection. In the separated lymphocytes of i. asymptomatic HIV positive persons; ii. HIV negative homosexuals; iii. atopic patients; and iv. healthy controls, expression of mRNA for IFNg (Th1) and IL-10 (Th2) were determined by semiquantitative RT-PCR. The serum level of antibodies for HIV 1/2 and total/specific IgE were also determined. Transcription of mRNA of IFNg and IL-10 were more pronounced in HIV positive and atopic groups than in the healthy control, without lymphocyte phenotype dominance. In HIV negative persons, however, a significant Th2 dominance was detected. There was no significant difference in the IgE level between the 4 investigated groups. In the HIV positive cases, IL-10 expression and total serum IgE do not support a switch to Th2 dominance. In the atopic group, aside from the total IgE level, down regulation of IFNg was not observed. These results suggest a general activation of the immune system in the early stage of HIV infection.
C1 [Barabas, Eva] National Institute for Dermato-Venereology, Maria str. 41, H-1085 Budapest, Hungary.
[Falus, Andras] Semmelweis University of Medicine, Biological InstituteBudapest, Hungary.
[Nagy, Karoly] National Institute for Dermato-Venereology, Maria str. 41, H-1085 Budapest, Hungary.
[Varkonyi, Viktoria] National Institute for Dermato-Venereology, Maria str. 41, H-1085 Budapest, Hungary.
[Temesvari, Erzsebet] National Institute for Dermato-Venereology, Maria str. 41, H-1085 Budapest, Hungary.
[Horvath, Attila] National Institute for Dermato-Venereology, Maria str. 41, H-1085 Budapest, Hungary.
RP Horvath, A (reprint author), National Institute for Dermato-Venereology, H-1085 Budapest, Hungary.
EM aurelius@bor.sote.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 68
EP 73
PG 6
ER
PT J
AU Casabona, J
Gambus, G
Vall, M
Rodes, A
AF Casabona, Jordi
Gambus, Gemma
Vall, Marti
Rodes, Anna
TI Risk Factors for AIDS Associated Kaposi's Sarcoma An European Multicentre Case Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE AIDS; Kaposi's sarcoma; risk factors; case-control study
ID AIDS; Kaposi's sarcoma; risk factors; case-control study
AB EURO-SHAKS, European study on HIV associated Kaposi's sarcoma, is a BIOMED 1 project financed by the European Union (DG XII). The Spanish side of the project has been financed by FISS (Fondo de Investigaciones Sanitarias). The aims of this study are to identify possible genetic, behavioural, biological and environmental risk factors for HIV associated Kaposi's sarcoma through a multicentre case-control study. An extensive personal questionnaire, a clinical data form and blood sample is required from all participants. In addition, a cutaneous biopsy is request from KS patients. The presence of several European groups in this project implies a large and diverse sample size and will allow to correlate the behaviour, clinical and biological data in different geographical areas, and therefore study the possible transmission routes as well as the natural history of the putative causal agent of KS. One of the main objectives of EURO-SHAKS is to create a European Bank of AIDS biological samples for possible future investigations.
C1 [Casabona, Jordi] Hopital Universitari Germans Trias i Pujol. Crta Canyet, 08916 Badalona, Spain.
[Gambus, Gemma] Hopital Universitari Germans Trias i Pujol. Crta Canyet, 08916 Badalona, Spain.
[Vall, Marti] Hopital Universitari Germans Trias i Pujol. Crta Canyet, 08916 Badalona, Spain.
[Rodes, Anna] Hopital Universitari Germans Trias i Pujol. Crta Canyet, 08916 Badalona, Spain.
RP Casabona, J (reprint author), Hopital Universitari Germans Trias i Pujol. Crta Canyet, 08916 Badalona, Spain.
EM jcasabona@ceescat.hugtip.scs.es
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 1997
VL 3
IS 1
BP 74
EP 77
PG 4
ER
PT J
AU Hagmann, W
AF Hagmann, Wolfgang
TI 12-Lipoxygenase in Human Tumor Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE epidermal growth factor; 12-lipoxygenase; metastasis; nuclear translocation; tumor cells
ID epidermal growth factor; 12-lipoxygenase; metastasis; nuclear translocation; tumor cells
AB Tumor cell proliferation and metastasis proceed via a network of interdependent molecular events with a vast array of molecular players and signal transduction mechanisms differing in various types of human tumors. In the sequence of events necessary for carcinogenesis, arachidonate metabolites have been documented to play a significant role at several steps. Arachidonate metabolism in human cells occurs via several enzymatic pathways, including enzymes such as cyclo-oxygenases and lipoxygenases. This review pays particular attention to one member of the lipoxygenase family of enzymes, namely 12-lipoxygenase, since an arachidonate metabolite generated via 12-lipoxygenase action, 12(S)-HETE, has been shown to elicit various prometastatic effects of tumor cells in vivo and in vitro. We focus especially on mechanisms of activation and modulation of 12-lipoxygenase expression in human tumor cells, since various tumor cells express 12-lipoxygenase or are responsive to metabolites derived from 12-lipoxygenase action, thus offering a potential for successful therapeutic intervention against such tumors.
C1 [Hagmann, Wolfgang] Deutsches Krebsforschungszentrum, Division of Tumor Biochemistry, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
RP Hagmann, W (reprint author), Deutsches Krebsforschungszentrum, Division of Tumor Biochemistry, D-69120 Heidelberg, Germany.
EM W.Hagmann@DKFZ-Heidelberg.de
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 83
EP 88
PG 6
ER
PT J
AU Lah, TT
Kos, J
Blejec, A
Frkovic-Georgio, S
Golouh, R
Vrhovec, I
Turk, V
AF Lah, T Tamara
Kos, Janko
Blejec, Andrej
Frkovic-Georgio, Snezana
Golouh, Rastko
Vrhovec, Ivan
Turk, Vito
TI The Expression of Lysosomal Proteinases and Their Inhibitors in Breast Cancer: Possible Relationship to Prognosis of the Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; cathepsin B; cathepsin D; cathepsin L; lysosomal enzymes; metastasis; prognostic factors; stefins
ID breast cancer; cathepsin B; cathepsin D; cathepsin L; lysosomal enzymes; metastasis; prognostic factors; stefins
AB Proteolytic enzymes have been proposed as new biological prognostic indicators to facilitate decisions about treatment of breast cancer patients following surgery. We reported earlier that the activities of cysteine proteinases (CP), cathepsin (Cat) B and cathepsin (Cat) L and the expression of stefin A might be associated with breast tumor progression and prognosis. Here, the protein concentrations of Cats D, B and L and stefin A have been measured in a series of 60 matched pairs of breast tumours and control adjacent tissues, using ELISAs developed in our laboratory. Median tumor concentrations of Cat D (47 pm/mg), Cat B (222 ng/mg) and Cat L (88 ng/mg) were significantly (p<0.0005) increased by 7 fold, 27 fold and 6 fold, respectively. Much greater increases in the activities of Cat B (63 fold) and of Cat L (274 fold) were found, indicating enhanced activation of cysteine proteinases in tumors, due either to proteolytic activation of proCat B and proCat L and/or to a decrease in specific endogenous cystatins. However, the 1.6-fold decreased (p<0.0001) levels of inhibition by cystatins could not be entirely responsible for more than 100-fold increased ratio of CP:cystatins activity. Moreover, stefin A was either increased or decreased in tumor samples, resulting in a 1.4-fold median increase in tumors. Comparing the biological parameters with the established histo-pathological prognosticators, we found that the increased protein concentration of Cat B was associated with lymph node involvement (p<0.009) and higher stage (p<0.003), and both Cat B and Cat L activities were more increased in high grade tumours (p<0.05). Survival analysis revealed that stefin A was the most significant prognostic factor for disease-free (p<0.008) and overall survival (p<0.02), followed by increased Cat B activity and protein concentration. Cat L was of borderline significance while Cat D was not significant for prognosis. We conclude that enhanced activation of CP, due partially to an imbalance between cysteine proteinases and inhibitors is linked to the progression of breast cancer. Larger sample size is needed to confirm the prognostic significance of stefin A, Cat B and Cat L.
C1 [Lah, T Tamara] National Institute of Biology, Laboratory of Molecular Biology and Biochemistry, Vecna pot 111, 1000 Ljubljana, Slovenia.
[Kos, Janko] National Institute of Biology, Laboratory of Molecular Biology and BiochemistryLjubljana, Slovenia.
[Blejec, Andrej] National Institute of Biology, Laboratory of Molecular Biology and Biochemistry, Vecna pot 111, 1000 Ljubljana, Slovenia.
[Frkovic-Georgio, Snezana] Institute of Oncology, Department of PathologyLjubljana, Slovenia.
[Golouh, Rastko] Institute of Oncology, Department of PathologyLjubljana, Slovenia.
[Vrhovec, Ivan] Institute of Oncology, Department of PathologyLjubljana, Slovenia.
[Turk, Vito] National Institute of Biology, Laboratory of Molecular Biology and BiochemistryLjubljana, Slovenia.
RP Lah, TT (reprint author), National Institute of Biology, Laboratory of Molecular Biology and Biochemistry, 1000 Ljubljana, Slovenia.
EM tamara.lah@ijs.si
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 89
EP 99
PG 11
ER
PT J
AU Mihalik, R
Uher, F
Petak, I
Sebestyen, A
Kopper, L
AF Mihalik, Rudolf
Uher, Ferenc
Petak, Istvan
Sebestyen, Anna
Kopper, Laszlo
TI Regulation of Differentiation, Proliferation and Drug-Induced Apoptosis in HT58 Lymphoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; lymphoma; differentiation; etoposide; staurosporine; PMA
ID apoptosis; lymphoma; differentiation; etoposide; staurosporine; PMA
AB Recently, it has been suggested, that differentiated cells are more resistant to the apoptotic effect of DNA damaging agents possibly due to the decreased activity of ''damage detecting / apoptosis triggering'' mechanism. Previously, we have shown, that PMA pretreatment reduced etoposide- (ETO) but enhanced staurosporine- (STA) -induced apoptosis in HT58 cells. Data presented here show that the HT58 human, ''mature'' B-lymphoma cells exposed to PMA secrete more IgM into the supernatant indicating commitment of cells to perform differentiated function. The sensitivity of HT58 cells to ETO- or STA-induced apoptosis is influenced diversely with PMA pre- or posttreatment. Interestingly, the DNA damage (gamma radiation, bleomycin, ETO) or okadaic acic (30 nM) reduced the [PMA+STA] - induced apoptosis.
C1 [Mihalik, Rudolf] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Uher, Ferenc] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Petak, Istvan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 100
EP 105
PG 6
ER
PT J
AU Kapustin, IS
Popova, IT
Lyschov, AA
Togo, VA
Abdulkadyrov, MK
Blinov, NM
AF Kapustin, I Sergey
Popova, I Tamara
Lyschov, A Anton
Togo, V Alexander
Abdulkadyrov, M Kudrat
Blinov, N Michail
TI HLA-DR2 Frequency Increase in Severe Aplastic Anemia Patients is Mainly Attributed to the Prevalence of DR15 Subtype
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE aplastic anemia; HLA-DR antigens; DNA extraction
ID aplastic anemia; HLA-DR antigens; DNA extraction
AB The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.
C1 [Kapustin, I Sergey] Institute of Haematology and Transfusiology, Laboratory of Biochemistry, 2nd Sovietskaya st. 16, 193024 Saint-Petersburg, Russian Federation.
[Popova, I Tamara] Institute of Haematology and Transfusiology, Laboratory of Biochemistry, 2nd Sovietskaya st. 16, 193024 Saint-Petersburg, Russian Federation.
[Lyschov, A Anton] NN Petrov Institute of Oncology, Department of Molecular OncologySaint-Petersburg, Russian Federation.
[Togo, V Alexander] NN Petrov Institute of Oncology, Department of Molecular OncologySaint-Petersburg, Russian Federation.
[Abdulkadyrov, M Kudrat] Institute of Haematology and Transfusiology, Laboratory of Biochemistry, 2nd Sovietskaya st. 16, 193024 Saint-Petersburg, Russian Federation.
[Blinov, N Michail] Institute of Haematology and Transfusiology, Laboratory of Biochemistry, 2nd Sovietskaya st. 16, 193024 Saint-Petersburg, Russian Federation.
RP Blinov, NM (reprint author), Institute of Haematology and Transfusiology, Laboratory of Biochemistry, 193024 Saint-Petersburg, Russian Federation.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 106
EP 108
PG 3
ER
PT J
AU Cserni, G
AF Cserni, Gabor
TI Changes in Benign to Malignant Ratio of Surgically Treated Breast Diseases in a District Hospital
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE benign to malignant ratio; breast; fine-needle aspiration cytology; mammography
ID benign to malignant ratio; breast; fine-needle aspiration cytology; mammography
AB The benign to malignant ratio (BMR) of open surgical biopsies is often used to monitor the efficacy of diagnostic workup of breast lesions. Avoiding the unnecessary removal of benign lesions is of recognized importance. Histopathology archives of the Department of Pathology of the Bacs-Kiskun County Hospital were retrieved for breast lesions and the BMR of surgical specimens was determined for each year between the period of 1965-1996. The introduction of mammography and especially fine-needle aspiration cytology was paralleled by a reduction in the benign to malignant ratio from 1.7 to 0.7. Only the introduction of breast aspiration cytology seemed to have a significant effect on the BMR, but the more adequate diagnostic approach to breast lesions (mostly palpable in their nature) was in part masqueraded by the late shift in attitude of both surgeons and patients towards breast lumps. This is why the BMR can give a basic information on preoperative diagnostic workup of breast lesions, but in itself it is not able to monitor them.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 109
EP 114
PG 6
ER
PT J
AU Sztan, M
Papai, Zs
Szendroi, M
Van Der Looij, M
Olah, E
AF Sztan, Marianna
Papai, Zsuzsa
Szendroi, Miklos
Van Der Looij, Marco
Olah, Edit
TI Allelic Losses from Chromosome 17 in Human Osteosarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chromosome 17; TP53; tumor suppressor gene; loss of heterozygosity; osteosarcoma
ID chromosome 17; TP53; tumor suppressor gene; loss of heterozygosity; osteosarcoma
AB Genetic alterations of chromosome 17 have been reported to occur frequently both in human sporadic and familial malignancies. The present study was undertaken to explore the possible involvement of chromosome 17 genes including TP53 and the breast cancer susceptibility BRCA1 tumor suppressor genes in the development of sporadic osteogenic sarcoma. Fifteen patients were screened by polymerase chain reaction (PCR) for loss of heterozygosity (LOH) using four highly polymorphic markers. Loss of heterozygosity at the TP53 locus was detected in 40% (6/15) of informative cases while it was 14% (2/14) at the locus of thyroid hormone receptor alpha (THRA1), 21% (3/14) at the D17S855 locus intragenic to BRCA1 and 27% (4/15) at the D17S579 locus. In 53% of the cases studied at least one locus on chromosome 17 was affected by LOH. In our panel, the overall LOH frequency on 17p and 17q was observed to be 40% (6/15) and 27% (4/15), respectively. Comparison of LOH frequencies with clinical and prognostic features revealed significant correlation only with tumor recurrence. Our results confirm that the role of the TP53 tumor suppressor gene is important in the pathogenesis of sporadic osteosarcoma and suggest that 17q12-21 region abnormalities may be involved in the development and/or progression of this tumor.
C1 [Sztan, Marianna] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1525 Budapest, Hungary.
[Papai, Zsuzsa] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Van Der Looij, Marco] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1525 Budapest, Hungary.
[Olah, Edit] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1525 Budapest, Hungary.
RP Olah, E (reprint author), National Institute of Oncology, Department of Biochemistry, H-1525 Budapest, Hungary.
EM e.olah@oncol.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 115
EP 120
PG 6
ER
PT J
AU Tsyplakov, ED
Petrov, VS
Kulagin, NR
AF Tsyplakov, E Dmitry
Petrov, V Semion
Kulagin, N Roman
TI Lymph Node Reaction to Cancer (Immunohistochemical and Ultrastructural Study)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lymph node; cancer; immunohistochemistry
ID lymph node; cancer; immunohistochemistry
AB A total of 153 regional lymph nodes obtained from 50 patients, operated for gastric, lung, breast, colonic and cervical cancers, were studied. Immunohistochemical methods were used to detect different markers and enzymes (CD1, CD2, CD3, CD4, CD8, CD20, CD30, CD35, CD45, l light Ig chain, lysozyme (muramidase), a-1-antichymotrypsin, protein S100 and FVIIIR). Results indicate that failure of local immunity is explained by the followings: 1. decrease in the total number of T-cells (suppressors as well as helpers); 2. high number of B-cells, plasmoblasts and antibody-forming plasmocytes, know to be able to block the cytotoxic T cells; 3. decrease in the number of incoming free phagocytes of monocytic origin and reduction in the phagocytic activity of fixed macrophages (sinus histiocytes); 4. high functional activity of dendritic reticulum cells; 5. non-handled stimulation of T cell response by the paracortical interdigitating reticulum cells; 6. reduction in area of postcapillary venules and impairment of lymphocyte recirculation through them.
C1 [Tsyplakov, E Dmitry] Medical University, Department of Pathology, Butlerov str 49, 420012 Kazan, Russian Federation.
[Petrov, V Semion] Kazan Cancer CenterKazan, Russian Federation.
[Kulagin, N Roman] Medical University, Department of Pathology, Butlerov str 49, 420012 Kazan, Russian Federation.
RP Tsyplakov, ED (reprint author), Medical University, Department of Pathology, 420012 Kazan, Russian Federation.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 121
EP 125
PG 5
ER
PT J
AU Jablonska, E
Piotrowski, L
Grabowska, Z
AF Jablonska, Ewa
Piotrowski, Leszek
Grabowska, Zyta
TI Serum Levels of IL-1b, IL-6, TNF-a, sTNF-RI and CRP in Patients with Oral Cavity Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE oral cancer; IL-1b; IL-6; TNF-a; sTNF-RI; CRP; SCC
ID oral cancer; IL-1b; IL-6; TNF-a; sTNF-RI; CRP; SCC
AB Pro-inflammatory cytokines, such as interleukin-1b (IL-1b), interleukin-6 (IL-6) and tumor necrosis factor- (TNF-a) play an essential role in the regulation of immune response to, and may have prognostic significance in, cancer. The aim of this study was to examine the relationship between the serum levels of IL-1b, IL-6 and TNF-a as well as the concentrations of soluble TNF receptor I (sTNF-RI) and C-reactive protein (CRP) in patients with squamous cell carcinoma of oral cavity. Results obtained were confronted with squamous cell carcinoma antigen (SCC) concentrations. IL-1b IL-6 and TNF-a serum levels as well as sTNF-RI and CRP concentrations were higher in patients than in controls. The increased serum levels appeared to be related to the clinical stage of disease. There was a correlation between IL-1b and sTNF-RI. IL-6 and IL-1b correlated with CRP levels. The mean concentrations of SCC were also elevated. IL-6 and sTNF-RI seemed to be the most sensitive parameters in early stages and may be used as additional markers in oral cancer.
C1 [Jablonska, Ewa] Medical Academy, Department of Immmunopathology, Kilinski 1., 15-230 Bialystok, Poland.
[Piotrowski, Leszek] Medical Academy, Deparment of Oral and Maxillofacial SurgeryBialystok, Poland.
[Grabowska, Zyta] Medical Academy, Department of Immmunopathology, Kilinski 1., 15-230 Bialystok, Poland.
RP Jablonska, E (reprint author), Medical Academy, Department of Immmunopathology, 15-230 Bialystok, Poland.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 126
EP 129
PG 4
ER
PT J
AU Ibanez-Manlapaz, GI
McCoy, D
Vincent, IV
Ule, JU
AF Ibanez-Manlapaz, G Irene
McCoy, David
Vincent, III Vincent
Ule, Jo Ulla
TI Malignant Mixed Mullerian Tumor of the Extra-genital Coelomic Epithelium: Report of Two Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE extra-genital mullerian tumor; carcinosarcoma; poor prognosis; female peritoneum
ID extra-genital mullerian tumor; carcinosarcoma; poor prognosis; female peritoneum
AB Malignant mixed mullerian tumors of the extra-genital coelomic epithelium (female peritoneum) are rare. Since the first case report in 1955, only nineteen have been described. In our Case 1 a 58 year-old G3P3 (gravidity = 3; parity = 3) white female with mixed mullerian tumor, homologous type, involving the abdominal peritoneum was treated with surgery and chemotherapy (doxorubicin hydrochloride and cis-platinum). She died of the disease 20 months after initial surgery. Case 2 is a 75 year-old G0P0 (gravidity = 0; parity = 0) white female with mixed mullerian tumor containing heterologous elements involving the pelvic peritoneum who was treated with surgery and chemotherapy (ifosfamide with mesna). She relapsed 6 months after surgery and refused any further treatment. She died 2 weeks later. These cases support the fact that malignant mixed mullerian tumor of the female peritoneum is rare and usually affects elderly females. It has poor prognosis and among the 15 reported cases with follow-up indicating time and presence of disease at death, only 5 survived more than 12 months after initial surgery.
C1 [Ibanez-Manlapaz, G Irene] St. Frances Cabrini Hospital, Department of Pathology, 3330 Masonic Drive, 71301 Alexandria, Alexandria, USA.
[McCoy, David] St. Frances Cabrini Hospital, Department of SurgeryAlexandria, Alexandria, USA.
[Vincent, III Vincent] St. Frances Cabrini Hospital, Department of Obstetrics & GynecologyAlexandria, Alexandria, USA.
[Ule, Jo Ulla] St. Frances Cabrini Hospital, Department of MedicineAlexandria, Alexandria, USA.
RP Ibanez-Manlapaz, GI (reprint author), St. Frances Cabrini Hospital, Department of Pathology, 71301 Alexandria, USA.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 130
EP 134
PG 5
ER
PT J
AU Varkonyi, J
Jakab, L
Zalatnay, A
Nagy, P
Vamos, R
Szombathy, T
AF Varkonyi, Judit
Jakab, Lajos
Zalatnay, Attila
Nagy, Peter
Vamos, Rita
Szombathy, Tamas
TI Polychondritis Terminating in Eosinophilic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE relapsing polychondritis; vitiligo; myelodysplasia; eosinophilia; eosinophil leukemia
ID relapsing polychondritis; vitiligo; myelodysplasia; eosinophilia; eosinophil leukemia
AB We report here on a patient presenting with Relapsing Polychondritis (RP) two years before the diagnosis of Myelodysplasia (MDS) terminating in Eosinophilic Leukemia (EoL). The evolution of RP several years prior to the presentation of MDS does not support a paraneoplastic etiology of RP in this patient. The terminal development of EoL in our case is assumed to represent clonal evolution caused by a second mutagenic event. The existence of autoimmune skin disorders in both the patient and his offspring (vitiligo and subacute cutaneous lupus erythematosus, respectively) implies that the coexistence of MDS and RP may have been caused by a functional disturbance of the immune system.
C1 [Varkonyi, Judit] Semmelweis University, 3rd Department of Internal Medicine, 12 Eotvos ut, H-1121 Budapest, Hungary.
[Jakab, Lajos] Semmelweis University, 3rd Department of Internal Medicine, 12 Eotvos ut, H-1121 Budapest, Hungary.
[Zalatnay, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Nagy, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Vamos, Rita] Semmelweis University, Department of OphthalmologyBudapest, Hungary.
[Szombathy, Tamas] Semmelweis University, 3rd Department of Internal Medicine, 12 Eotvos ut, H-1121 Budapest, Hungary.
RP Varkonyi, J (reprint author), Semmelweis University, 3rd Department of Internal Medicine, H-1121 Budapest, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 135
EP 138
PG 4
ER
PT J
AU Vadasz, G
Sapi, Z
Erdei, M
Lovey, Gy
Bodo, M
AF Vadasz, Gizella
Sapi, Zoltan
Erdei, Mihaly
Lovey, Gyorgy
Bodo, Miklos
TI Spontaneously curing anaplastic carcinoma in the lymph node
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE anaplastic carcinoma; spontaneous regression
ID anaplastic carcinoma; spontaneous regression
AB A well documented case of a spontaneously curing anaplastic carcinoma in lymph node is presented with a 16 year follow up. Reevaluation and detailed immunohistochemical examination confirmed the original diagnosis of anaplastic carcinoma. This is the first report of a spontaneously curing anaplastic carcinoma which raises the following questions: Was the tumor in the axillary lymph node a metastasis or a primary tumor? Does the anaplastic carcinoma demonstrate the same spontaneous regression characteristics as for example the neuroblastoma?
C1 [Vadasz, Gizella] St John's Hospital, Department of Pathology, Diosarok u. 1., H-1125 Budapest, Hungary.
[Sapi, Zoltan] St John's Hospital, Department of Pathology, Diosarok u. 1., H-1125 Budapest, Hungary.
[Erdei, Mihaly] General PractitionerBudapest, Hungary.
[Lovey, Gyorgy] St. Francis Hospital, Department of SurgeryBudapest, Hungary.
[Bodo, Miklos] St John's Hospital, Department of Pathology, Diosarok u. 1., H-1125 Budapest, Hungary.
RP Vadasz, G (reprint author), St John's Hospital, Department of Pathology, H-1125 Budapest, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 139
EP 141
PG 3
ER
PT J
AU Tozser, J
AF Tozser, Jozsef
TI Specificity of Retroviral Proteinases Based on Substrates Containing Tyrosine and Proline at the Site of Cleavage
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE proteinases; retroviral; HIV; cleavage; specificity
ID proteinases; retroviral; HIV; cleavage; specificity
AB The retroviral proteinase (PR) plays crucial roles in the viral life cycle, therefore it is a target for chemotherapy. However, resistance rapidly develops due to frequent mutations. Studies to determine the common features of the specificity of different retroviral PRs may help to design broad spectrum inhibitors and reduce the possibility of viable mutants. We have studied the specificity of various retroviral proteinases including those the PR of HIV-1, HIV-2, equine infectious anemia virus and avian myeloblastosis virus using oligopeptide substrates. A series of oligopeptides containing substitutions in a sequence Val-Ser-Gln-Asn-Tyr*Pro-Ile-Val-Gln (asterisk indicates the site of cleavage) representing a naturally occurring cleavage site in HIV-1 was used to characterize the seven substrate binding subsites of the enzymes. The unsubstituted substrate is a typical class 1 cleavage site substrate containing an aromatic amino acid and a proline residue at the site of cleavage. The largest differences in kinetics of substrate hydrolysis were obtained with peptides containing substitutions of the Ser and Asn residues. Detailed analysis of the results by molecular modeling and comparison with previously reported data revealed the common characteristics of the specificity of the PRs as well as its strong dependence on the sequence context of the substrate. However, molecular modeling in many cases provided explanation for the sequence context dependence. Also, comparison of the specificity of the enzymes suggests that the specificity of HIV-1 and -2 PRs is rather exceptional preferring hydrophilic residues at the most discriminative positions while other PRs prefer hydrophobic residues.
C1 [Tozser, Jozsef] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98., H-4012 Debrecen, Hungary.
RP Tozser, J (reprint author), University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, H-4012 Debrecen, Hungary.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 142
EP 146
PG 5
ER
PT J
AU Aszalos, A
Eckhardt, S
AF Aszalos, Adorjan
Eckhardt, Sandor
TI Molecular Events as Targets of Anticancer Drug Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE cancer; molecular targets; chemotherapy
ID cancer; molecular targets; chemotherapy
AB The aim of this review is to introduce some molecular targets for cancer chemotherapy, with comments on their mode of action, preclinical and clinical results. The representatives of the following groups are covered: phosphorylation inhibitors, protein kinase modulators, receptor antagonists, immunomodulators, differentiating agents, multidrug resistance modulation, telomerase inhibitors, and bioreductive agents.
C1 [Aszalos, Adorjan] Food and Drug Administration, 200 C Street, 20204 Washington, SW, USA.
[Eckhardt, Sandor] National Institute of OncologyBudapest, Hungary.
RP Aszalos, A (reprint author), Food and Drug Administration, 20204 Washington, USA.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 1997
VL 3
IS 2
BP 147
EP 158
PG 12
ER
PT J
AU Schweighoffer, T
AF Schweighoffer, Tamas
TI Molecular Cancer Vaccines: Tumor Therapy Using Antigen-Specific Immunizations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE vaccines; molecular; immunotherapy; tumor
ID vaccines; molecular; immunotherapy; tumor
AB Vaccination against tumors promises selective destruction of malignant cells by the host's immune system. Molecular cancer vaccines rely on recently identified tumor antigens as immunogens. Tumor antigens can be applied in many forms, as genes in recombinant vectors, as proteins or peptides representing T cell epitopes. Analysis of various aspects indicates some advantage for peptide-based vaccines over the other modalities. Further refinements and extensively monitored clinical trials are necessary to advance molecular cancer vaccines from concepts into powerful therapy.
C1 [Schweighoffer, Tamas] Boehringer Ingelheim Research and Development, Department Cell Biology, Dr. Boehringer-Gasse 5, A-1120 Vienna, Austria.
RP Schweighoffer, T (reprint author), Boehringer Ingelheim Research and Development, Department Cell Biology, A-1120 Vienna, Austria.
EM schweig@bender.co.at
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 164
EP 176
PG 13
ER
PT J
AU Lewin, JK
AF Lewin, J Klaus
TI Post-transplant Lymphoproliferative Disorders
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE post-transplant; lymphoproliferation
ID post-transplant; lymphoproliferation
AB Post-transplant lymphoproliferative disorder (PTLD) is one of the most dreaded complications of orthotopic transplantation. It consists of a heterogeneous group of lymphoproliferative disorders of varying clonal composition, occurring in immunosuppressed organ allograft recipients and is frequently due to EBV infection. It is most common in heart/lung transplants followed by heart, liver, and kidney and rarely in bone marrow transplants. Clinically, PTLD can present in a number of ways ranging from features resembling infectious mononucleosis, lymphoproliferative masses involving both nodal and extranodal locations, to a fulminant form characterized by a combination of peripheral lymphadenopathy, severe metabolic acidosis, organ failure or allograft dysfunction. Pathologically PTLD is characterized by a dense inflammatory infiltrate with a spectrum ranging from that found in infectious mononucleosis to a polymorphous B-cell hyperplasia to that of a monomorphous lymphoma. Analysis of EBV is especially useful for the diagnosis of early cases of PTLD. In addition, immunophenotyping to determine the lymphocyte type (B or T cell type) and monoclonality are most helpful in determining the prognosis.
C1 [Lewin, J Klaus] University of Southern California, Keck Medical Center, Department of Pathology, 10833 Le Conte Ave, 90095-1732 Los Angeles, CA, USA.
RP Lewin, JK (reprint author), University of Southern California, Keck Medical Center, Department of Pathology, 90095-1732 Los Angeles, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 177
EP 182
PG 6
ER
PT J
AU Kopper, L
Sebestyen, A
Gallai, M
Kovalszky, I
AF Kopper, Laszlo
Sebestyen, Anna
Gallai, Monika
Kovalszky, Ilona
TI Syndecan-1 - A New Piece in B-cell Puzzle
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE syndecan-1; heparan sulfate; proteoglycan; hematopoietic cells; B-cells
ID syndecan-1; heparan sulfate; proteoglycan; hematopoietic cells; B-cells
AB Syndecans are transmembrane proteoglycans, with core proteins mainly decorated with heparan sulfate chains. Syndecan-1 is expressed in a tissue-, cell- and differentiation-specific manner. Its extracellular domain can bind via HS chains to matrix elements, to growth factors (especially ''heparin-binding'' proteins) and to certain biological agents. The ectodomain released by proteolysis can also be functionally active. The cytoplasmic domain can take part in signaling processes as well as in modifying cell shape. In hematopoietic cells syndecan-1 is expressed in normal pre-B-cells and plasma cells, as well as in plasmocytoid and lymphoplasmocytoid malignancies. According to our study syndecan-1 is expressed in B-CLL cells both in tissue environment and in circulation.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Gallai, Monika] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 183
EP 191
PG 9
ER
PT J
AU Kovacs, GG
Majtenyi, K
Laszlo, L
AF Kovacs, G Gabor
Majtenyi, Katalin
Laszlo, Lajos
TI Prion Protein Immunohistochemistry in Creutzfeldt-Jakob Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Creutzfeldt-Jakob disease; prion protein; immunohistochemistry
ID Creutzfeldt-Jakob disease; prion protein; immunohistochemistry
AB Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized clinically by dementia, myoclonus and, in some cases, periodic triphasic EEG-patterns. Neuropathologically the main features are spongiform change, astrocytosis, neuronal cell loss and, in a small percent of cases, amyloid plaques. Prion protein immunohistochemistry is used for definitive diagnosis of these diseases. In our study we present different immunostaining patterns in light microscopy using anti prion protein, and with immunogold labelling for ultrastructural localization of prion protein. Our results demonstrate the clinicopathological heterogeneity of Creutzfeldt-Jakob disease and reveal the role of the endosomal-lysosomal system in the pathogenesis.
C1 [Kovacs, G Gabor] Semmelweis University of Medicine, Department of NeurologyBudapest, Hungary.
[Majtenyi, Katalin] National Institute of Psychiatry and Neurology, Department of NeuropathologyBudapest, Hungary.
[Laszlo, Lajos] Eotvos University, Department of General Zoology, H-1445 Budapest, Hungary.
RP Laszlo, L (reprint author), Eotvos University, Department of General Zoology, H-1445 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 193
EP 197
PG 5
ER
PT J
AU Shan, L
Kakudo, K
Nakamura, M
Nakamura, Y
Yokoi, T
Ishimoto, J
Kawahara, K
Takami, H
AF Shan, Liang
Kakudo, Kennichi
Nakamura, Misa
Nakamura, Yasushi
Yokoi, Toyoharu
Ishimoto, Junya
Kawahara, Katsuhiko
Takami, Hiroshi
TI Clonality of the Parathyroid Nodules with Uremic Parathyroid Hyperplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE parathyroid adenoma; uremic parathyroid hyperplasia; clonality; PGK gene
ID parathyroid adenoma; uremic parathyroid hyperplasia; clonality; PGK gene
AB Clonal assessment suggests that most parathyroid adenomas and a subset of uremic parathyroid hyperplasia are monoclonal. A weakness that remains in the prior clonal studies is assessing the clonal status of the tissue fragments containing multiple nodules rather than a single nodule emerging in the uremic parathyroid hyperplasia. We applied the X chromosome-linked phosphoglycerate kinase (PGK) gene inactivation assay method for clonality to study individual nodules. Materials were obtained from 31 cases with parathyroid adenoma and 16 with uremic parathyroid hyperplasia. 17 cases were heterozygous in the PGK-1 locus. We were able to assess the clonality of 10 parathyroid adenomas and 7 hyperplastic glands. Monoclonality was demonstrable in 9 of the 10 parathyroid adenomas and in 4 of the 7 hyperplastic glands. Further analysis of 11 individual nodules microdissected from 3 monoclonal and 1 polyclonal hyperplastic glands revealed that 6 nodules were monoclonal and 5 were polyclonal. Nodules arising in a hyperplastic gland could be of monoclonal or polyclonal origin. Polyclonal and monoclonal nodules coexisted within single glands. Our findings indicate a progression from generalized hyperplasia to a monoclonal tumor in uremic parathyroid hyperplasia. Comparing clonality with the parathyroid hormone (PTH) immunoreactivity and histological features, we found that monoclonal nodules showed a homogeneous immunoreactivity against PTH antibody, whereas most of the polyclonal nodules showed a heterogeneous staining. Classic morphological criteria alone was inadequate to distinguish a monoclonal from a polyclonal nodule.
C1 [Shan, Liang] Wakayama Medical College, Second Department of Pathology, 27 Kyubancho, 640 Wakayama, Wakayama, Japan.
[Kakudo, Kennichi] Wakayama Medical College, Second Department of Pathology, 27 Kyubancho, 640 Wakayama, Wakayama, Japan.
[Nakamura, Misa] Wakayama Medical College, Second Department of Pathology, 27 Kyubancho, 640 Wakayama, Wakayama, Japan.
[Nakamura, Yasushi] Wakayama Medical College, Second Department of Pathology, 27 Kyubancho, 640 Wakayama, Wakayama, Japan.
[Yokoi, Toyoharu] Wakayama Medical College, Second Department of Pathology, 27 Kyubancho, 640 Wakayama, Wakayama, Japan.
[Ishimoto, Junya] Ishimoto HospitalWakayama, Japan.
[Kawahara, Katsuhiko] Kyoritsu HospitalNagoya, Japan.
[Takami, Hiroshi] Teikyo University, Medical School, Department of SurgeryTeikyo, Japan.
RP Shan, L (reprint author), Wakayama Medical College, Second Department of Pathology, 640 Wakayama, Japan.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 198
EP 203
PG 6
ER
PT J
AU Csuka, O
Remenar,
Koronczay, K
Doleschall, Z
Nemeth, Gy
AF Csuka, Orsolya
Remenar, Eva
Koronczay, Krisztina
Doleschall, Zoltan
Nemeth, Gyorgy
TI Predictive Value of p53, Bcl2 and Bax in the Radiotherapy of Head and Neck Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiosensitivity; head and neck cancer; p53; Bcl2; Bax
ID radiosensitivity; head and neck cancer; p53; Bcl2; Bax
AB Radiation is known to induce DNA damage resulting in the onset of apoptosis. The apoptosis is modulated by p53, Bcl2 and Bax proteins. High level of wild type p53 is required for radiation induced apoptosis. The p53 status, therefore, may be a crucial determinant of radiosensitivity of tumor cells. Overexpression of Bcl2, however, inhibits apoptosis via hetero- and homodimeric interaction. Bax might function as a cell death effector molecule that is neutralized by Bcl2. The aim of the present study is to investigate the correlation between p53, Bcl2, Bax and c-myc levels and the clinical response of head and neck cancer patients to radiation. The base line and 30 GY gamma radiation induced values of p53, Bcl2, Bax and c-myc were estimated by Western blot in 40 biopsies of head and neck cancers. We found that the radiosensitivity of head and neck cancer patients depends on the ratio of p53, Bcl2 and Bax protein levels. High Bcl2 levels resulted in radioresistance of cancer patients. Overexpression of Bax and c-myc may ensure the radiosensitivity of head and neck cancer patients. Our studies indicate that prediction of radiation sensitivity of tumors could be based on the simultaneous evaluation of p53, Bax and Bcl2 levels.
C1 [Csuka, Orsolya] National Institute of Oncology, Rath gYorgy u. 7-9., H-1122 Budapest, Hungary.
[Remenar, Eva] National Institute of Oncology, Rath gYorgy u. 7-9., H-1122 Budapest, Hungary.
[Koronczay, Krisztina] National Institute of Oncology, Rath gYorgy u. 7-9., H-1122 Budapest, Hungary.
[Doleschall, Zoltan] National Institute of Oncology, Rath gYorgy u. 7-9., H-1122 Budapest, Hungary.
[Nemeth, Gyorgy] National Institute of Oncology, Rath gYorgy u. 7-9., H-1122 Budapest, Hungary.
RP Csuka, O (reprint author), National Institute of Oncology, H-1122 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 204
EP 210
PG 7
ER
PT J
AU Sergi, C
Willig, F
Thomsen, M
Herwart, FO
Krempien, B
AF Sergi, Consolato
Willig, Friedrich
Thomsen, Marc
Herwart, F Otto
Krempien, Burkhard
TI Bronchopneumonia Disguising Lung Metastases of a Painless Central Chondrosarcoma of Pubis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE lung metastasis; primary chondrosarcoma
ID lung metastasis; primary chondrosarcoma
AB Chondrosarcoma is a generally locally malignant chondroid-forming bone tumor with a low potential for distant metastases. A small and completely painless central chondrosarcoma of pubis metastasizing to the lungs in a 63-year-old woman with bronchopneumonia is reported. Here we emphasize the mimicry and low growth of the chondrosarcoma and the easiness with which the diagnosis in completely asymptomatic patients can be missed. Although painless chondrosarcoma metastasizing to lung is rather rare, this tumor should be always included in the differential diagnosis of malignancies in this age category.
C1 [Sergi, Consolato] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany.
[Willig, Friedrich] University of Heidelberg, Speyererhof LehrkrankenhausHeidelberg, Germany.
[Thomsen, Marc] University of Heidelberg, Department of Orthopedic SurgeryHeidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany.
[Krempien, Burkhard] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany.
RP Sergi, C (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM Consolato_Sergi@krzmail.krz.uni-heidelberg.de
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 211
EP 214
PG 4
ER
PT J
AU Lotz, G
Koltai, P
Schaff, Zs
AF Lotz, Gabor
Koltai, Pal
Schaff, Zsuzsa
TI Giant Cell Hepatitis in Adults
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE giant cell; hepatitis; adult
ID giant cell; hepatitis; adult
AB Giant cell hepatitis is a frequent reaction of the liver to different injuries in newborns and in childhood, but rare in adults. This form of hepatitis is often accompanied by cholestasis and shows fast progression to cirrhosis. In most cases autoimmune, metabolic, toxic or viral origin can be found, but sometimes the etiology remains hidden. This paper introduces two adult giant cell hepatitis cases. Hepatitis C virus infection was the possible origin in the first case and autoimmune disease in the other one.
C1 [Lotz, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Koltai, Pal] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 215
EP 218
PG 4
ER
PT J
AU Toth, J
Elek, G
AF Toth, Jozsef
Elek, Gabor
TI Histiocytic and T-cell Rich B-Cell Lymphoma (TCRBCL) of the Stomach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE B-cell lymphoma; gastric lymphoma; extranodal lymphoma; T-cell rich B-cell lymphoma; histiocyte-rich lymphoma; gastroscopy
ID B-cell lymphoma; gastric lymphoma; extranodal lymphoma; T-cell rich B-cell lymphoma; histiocyte-rich lymphoma; gastroscopy
AB Although stomach is a frequent site of extranodal lymphomas, histiocyte-rich TCRBCL has not yet been described there. Even histology of repeated gastrobiopsies of this uncommon, diffuse, large B-cell lymphoma may be inconclusive and partial gastrectomy cannot be avoided. It is only immunohistology (CD20, CD43, CD68) of the paraffin blocks from the resection specimen that can lead to the final diagnosis of intermediate grade malignant lymphoma.
C1 [Toth, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gy. U. 5-7., H-1122 Budapest, Hungary.
[Elek, Gabor] Central Railway Hospital and Polyclinic, Department of PathologyBudapest, Hungary.
RP Toth, J (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 219
EP 223
PG 5
ER
PT J
AU Tarjan, V
Ujhelyi, E
Szabo, J
Kellner, R
Krall, G
Gyuris,
Mihaly, I
Fust, G
AF Tarjan, Veronika
Ujhelyi, Eszter
Szabo, Janos
Kellner, Robert
Krall, Geza
Gyuris, Agnes
Mihaly, Ilona
Fust, George
TI Three Cases of HIV-1 Seroreversion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; transient seropositivity
ID HIV; transient seropositivity
AB Three patients were enrolled, two as hemophiliacs, and one with acute EBV infection. Serial serum samples of each patient were tested with at least 3 different HIV antibody EIA tests, an immunofluorescent test and two western blots (WB). In the third case, PCR and reverse transcriptase enzyme activity measurement were also done. One of the regularly checked serum samples of hemophiliac patients was reactive with different HIV screening and confirmatory assays. Their next blood samples, two weeks and one month later, respectively, were negative with the same tests. In Case 3. two and a half years after the first examination, the EIA tests results changed to negative, but the WB was still indeterminate. In the case of the two hemophiliac patients, the patients may have been exposed to HIV containing blood products (before 1985), but were not infected. Regular treatment with factor VIII concentrate, in which HIV antigens may be present, can boost the immune response and results in transient seropositivity. In the case of the EBV infected patient, the transient HIV seropositivity may be the consequence of EBV induced proliferation of anti-HIV-antibody producing B cell clones. During our ten year HIV confirmatory practice we tested more than 40000 samples, from which transient seropositivity were observed only in the three cases summarized in this paper.
C1 [Tarjan, Veronika] National Institute of Haematology, Blood Transfusion and Immunology, H-1518 Budapest, Hungary.
[Ujhelyi, Eszter] National Institute of Haematology, Blood Transfusion and Immunology, H-1518 Budapest, Hungary.
[Szabo, Janos] National Institute of Haematology, Blood Transfusion and Immunology, H-1518 Budapest, Hungary.
[Kellner, Robert] Blood Transfusion CenterBaja, Hungary.
[Krall, Geza] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Gyuris, Agnes] Orszagos Egeszsegbiztositasi PenztarBudapest, Hungary.
[Mihaly, Ilona] St. Laszlo HospitalBudapest, Hungary.
[Fust, George] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
RP Tarjan, V (reprint author), National Institute of Haematology, Blood Transfusion and Immunology, H-1518 Budapest, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 224
EP 228
PG 5
ER
PT J
AU Silletti, S
Paku, S
Raz, A
AF Silletti, Steve
Paku, Sandor
Raz, Avraham
TI Tumor Cell Motility and Metastasis. Autocrine Motility Factor as an Example of Ecto/Exoenzyme Cytokines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE migration; autocrine motility factor; neuroleukin; phosphohexose isomerase; metastasis
ID migration; autocrine motility factor; neuroleukin; phosphohexose isomerase; metastasis
AB Cellular locomotion plays a critical role in such normal processes as embryonic development, tissue segregation, as well as the infiltration of fibroblasts and vascular cells during wound repair and the inflammatory responses of the adult immune system. During tumor invasion and metastasis the processes of cell migration achieve dire significance. Disruption of normal homeostatic mechanisms to benefit the survival of the individual tumor cell is a common theme discovered during the characterization of factors once thought to be tumor-specific. One such molecule, tumor cell autocrine motility factor, was so described and has only recently been identified as a normal protein involved in intracellular glycolysis as well as implicated as an extracellular effector of normal cell functions including survival of certain populations of neurons. This molecule represents a member of the newly emerging family of intracellular enzymes whose disparate functions as extracellular mediators of cellular responses defines a new class of ecto/exoenzymes which play a role in normal cellular processes and are inappropriately utilized by tumor cells to elicit new survival strategies.
C1 [Silletti, Steve] The Scripps Research Institute, Departments of Immunology and Vascular BiologyLa Jolla, USA.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Raz, Avraham] Detroit Medical Center, Barbara Ann Karmanos Cancer Institute, 110 E. Warren Avenue, 48201 Detroit, Michigan, USA.
RP Raz, A (reprint author), Detroit Medical Center, Barbara Ann Karmanos Cancer Institute, 48201 Detroit, USA.
EM raza@kci.wayne.edu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 1997
VL 3
IS 3
BP 230
EP 254
PG 25
ER
PT J
AU Degott, C
AF Degott, Claude
TI Drug-Induced Liver Injury Cholestatic Injury, Acute and Chronic
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE cholestasis; drug-induced
ID cholestasis; drug-induced
AB Cholestasis is the failure of bile to reach duodenum due to three different mechanisms: a. alteration of bile secretion by hepatocytes into the canaliculus with or without liver cell damage; b. obstruction of the intrahepatic bile ducts caused by diseases of ductules or small/medium bile ducts; c. obstruction of extrahepatic bile ducts. This short review focuses on drugs which may induce cholestasis by any of these mechanisms.
C1 [Degott, Claude] Service D'Anatomie et de Cytologie Pathologique, 100 bd du Gal-Leclerc, 92118 Clichy, Cedex, France.
RP Degott, C (reprint author), Service D'Anatomie et de Cytologie Pathologique, 92118 Clichy, France.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 260
EP 263
PG 4
ER
PT J
AU Luo, J
Sharma, N
Seftor, AE
De Larco, J
Heidger, MP
Hendrix, JM
Lubaroff, MD
AF Luo, Jun
Sharma, Navesh
Seftor, A Elisabeth
De Larco, Joseph
Heidger, M Paul
Hendrix, JC Mary
Lubaroff, M David
TI Heterogeneous Expression of Invasive and Metastatic Properties in a Prostate Tumor Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostate cancer; invasion; metastasis; E-cadherin; heterogeneity
ID prostate cancer; invasion; metastasis; E-cadherin; heterogeneity
AB Cellular heterogeneity of neoplasia is well demonstrated in the Dunning R-3327 rat prostate adenocarcinoma. In this study, we measured the differential expression of invasive and metastatic properties of this prostate model by cloning from a heterogeneous parental cell line. Four cell clones were derived and characterized by morphological studies, E-cadherin expression, and invasive and metastatic potential. Three of the clones (clones 5A, 5C, and 5D) demonstrated a fibroblastic morphology and were anchored to the substrate by loose microvillous processes. The fourth clone (clone 5B) grew in tight clusters and displayed many closely spaced microvilli, long overlapping cytoplasmic regions with well-defined junctional complexes. The parental line (R3327-5) demonstrated a combination of both these growth patterns. E-cadherin expression was absent in clones 5A, 5C, and 5D and very prominent in clone 5B, when compared to the parental line. The absence of E-cadherin expression correlated with increased invasiveness, as measured in an in vitro invasion assay. Subcutaneous injections of clones 5A, 5C, and 5D yielded lung metastases and no primary tumors at the site of inoculation while clone 5B was tumorigenic and produced fewer lung metastases in vivo. These clones, therefore, provide a potential for studying a variety of molecules involved in prostate cancer invasion and metastasis, especially for the direct testing of the significance of E-cadherin expresssion in prostate cancer progression.
C1 [Luo, Jun] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[Sharma, Navesh] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[Seftor, A Elisabeth] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[De Larco, Joseph] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[Heidger, M Paul] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[Hendrix, JC Mary] University of Iowa, Department of Anatomy, 1-101 Bowen Science Building, 51 Newton Road, 52242-1109 Iowa City, IA, USA.
[Lubaroff, M David] The University of Iowa, Departments of Urology and Microbiology and the Veterans Affairs Medical CenterIowa City, USA.
RP Hendrix, JM (reprint author), University of Iowa, Department of Anatomy, 52242-1109 Iowa City, USA.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 264
EP 271
PG 8
ER
PT J
AU Kovacs, J
Gomba, Sz
Zilahy, M
AF Kovacs, Judit
Gomba, Szabolcs
Zilahy, Monika
TI Comparison of the morphology of renal cysts and cystic renal tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE renal cysts; renal tumors; tubular markers; cell proliferation; immunohistochemistry
ID renal cysts; renal tumors; tubular markers; cell proliferation; immunohistochemistry
AB Renal tumors appear uncommonly with cystic changes. They may develop due to necrosis though well-formed real cysts are also known. Such lesions may present problems in distinguishing them from benign renal cysts. Conditions leading to cyst formation are not known, however cell proliferation, altered extracellular matrix production and oncoprotein expression have been reported in cystic renal disorders. In the present study, we analysed the morphological features of 23 cystic renal tumors in comparison with 16 benign cysts using immunohistochemical and lectin binding methods. By our knowledge there has not been any piblication on such studies. The cystic renal tumors were represented predominantly in males and the size of the cysts was slightly larger than that of benign cysts. Tumorous cysts shared similar morphological appearance to solitary and multilocular cysts. They all showed strong epithelial membrane antigen reactivity on the luminal surface of the cells indicating distal tubular origin. Cell proliferation and p53 expression proved to be low excluding their role in the formation of the cysts. The amount of extracellular matrix and basement membrane was increased with an elevated type IV collagen and reduced fibronectin content. Polycystic kidney disease is different from tumorous cysts as cell proliferation, p53 oncoprotein expression and the composiition of extracellular matrix proved to be the opposite. As renal cell tumors arise from proximal tubules, neoplastic or metaplastic differentiation toward distal tubular direction seems to be the key even in cyst formation. Altered cell-matrix or cell-cell contact can modulate this transformation providing a basis for further results.
C1 [Kovacs, Judit] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
[Gomba, Szabolcs] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
[Zilahy, Monika] University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
RP Kovacs, J (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
EM kovacsj@lib.dote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 272
EP 277
PG 6
ER
PT J
AU Thomas, AP
Oykutlu, D
Pou, B
Tyler, D
Oberley, WL
Robinson, AR
Lenel, CJ
AF Thomas, A Patricia
Oykutlu, Dilek
Pou, Bel
Tyler, Denise
Oberley, W Larry
Robinson, A Robert
Lenel, C Julia
TI Immunohistochemical Characterization of Antioxidant Enzymes in Human Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; antioxidant enzymes; immunohistochemistry
ID Breast cancer; antioxidant enzymes; immunohistochemistry
AB Intrinsic antioxidant enzymes (AE) are essential for protection against potential cellular damage by free radicals (FRs), which affect a variety of biological processes. The levels or activities of AEs can be abnormal in human malignancies in general, and FR production is a possible mechanism of estrogen related carcinogenesis specifically. However, the role of AEs in breast cancer ramains unclear. Immunodetectable AEs were characterized in 95 node negative cancers using rabbit polyclonal antibodies. Results were correlated with established and experimental biomarkers of breast cancer. AEs were greater than benign differentiated epithelium in more than 40% and lower in 10-14% of tumors. Patterns of staining were enzyme and tumor pattern specific. Increased immunodetectable AE was associated with large, poorly differentiated tumors, and younger age. Catalase correlated with nuclear grade and disease related death (p< 0.05), and highlighted tumor microvasculature. Additional work in this area may further elucidate the role of AEs in breast cancer growth and progression.
C1 [Thomas, A Patricia] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Oykutlu, Dilek] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Pou, Bel] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Tyler, Denise] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Oberley, W Larry] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Robinson, A Robert] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
[Lenel, C Julia] University of Iowa, Department of Pathology, 5239 RCP;200 Hawkins Drive, 42242 Iowa City, Iowa, USA.
RP Thomas, AP (reprint author), University of Iowa, Department of Pathology, 42242 Iowa City, USA.
EM patricia-thomas@uiowa.edu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 278
EP 286
PG 9
ER
PT J
AU Cserni, G
Viragh, Sz
AF Cserni, Gabor
Viragh, Szabolcs
TI Immunohistochemical and Ultrastructural Analysis of a Mammary Cystic Hypersecretory Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE breast; cystic hypersecretory carcinoma; electronmicroscopy; immunohistochemistry
ID breast; cystic hypersecretory carcinoma; electronmicroscopy; immunohistochemistry
AB Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
[Viragh, Szabolcs] Haynal Imre University of Health Sciences, Institute of PathologyBudapest, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 287
EP 292
PG 6
ER
PT J
AU Ciardi, A
Pecorella, I
Trombetta, G
Memeo, L
De Quarto, A
Di Tondo, U
AF Ciardi, Antonio
Pecorella, Irene
Trombetta, Giorgio
Memeo, Lorenzo
De Quarto, Angeloluca
Di Tondo, Ugo
TI An Unusual Case of Neurofibroma of the Thyroid Capsule
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Visceral neurofibroma; peripheral nerve sheath tumors; thyroid capsule
ID Visceral neurofibroma; peripheral nerve sheath tumors; thyroid capsule
AB A solitary neurofibroma arising from the thyroid capsule in a 64 year-old woman is reported. The tumor was adherent to the lower margin of the thyroid gland and extended into the anterior mediastinum. The unusual nature of the lesion, both its relationship to the thyroid gland and to the occurrence of a neural tumor in the anterior mediastinum is discussed.
C1 [Ciardi, Antonio] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
[Pecorella, Irene] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
[Trombetta, Giorgio] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
[Memeo, Lorenzo] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
[De Quarto, Angeloluca] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
[Di Tondo, Ugo] University of Rome, Campus Bio-Medico, Department of Pathology, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
RP Ciardi, A (reprint author), University of Rome, Campus Bio-Medico, Department of Pathology, 00161 Rome, Italy.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 293
EP 295
PG 3
ER
PT J
AU Prohaszka, Z
Toth, DF
Banhegyi, D
Fust, G
AF Prohaszka, Zoltan
Toth, D Ferenc
Banhegyi, Denes
Fust, George
TI Role of Complement and Antibodies in the Control and Facilitation of HIV Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; complement; gp41; gp120; mannan-binding lectin; enhancing antibodies; autoantibodies; heat-shock protein 60; C1q
ID HIV; complement; gp41; gp120; mannan-binding lectin; enhancing antibodies; autoantibodies; heat-shock protein 60; C1q
AB In humans the HIV infection results in a chronic disease with a permanent fight between factors controlling HIV and the escape of the virus. Fromthese control mechanisms the present review summarizes the role betwen complement and autoantibodies; the competition of complement and anti-HIV antibodies for binding sites, the role of mannan-binding lectin in the susceptibility to and in the survival after HIV infection, the contribution of complement-dependent enhancing type antibodies to the clinical progression of HIV disease as well as the changing pattern of some autoantibodies (mimicking MHC class II molecules, anti-heat shock protein 60 antibodies and anti-C1q antibodies) which were found to correlate to immunological and clinical parameters.
C1 [Prohaszka, Zoltan] Semmelweis University, 3rd Department of Internal Medicine, Eotvos ut 12., H-1121 Budapest, Hungary.
[Toth, D Ferenc] University of Debrecen, Faculty of Medicine, Department of Medical MicrobiologyDebrecen, Hungary.
[Banhegyi, Denes] St. Istvan and St Laszlo Hospital, Immunology LaboratoryBudapest, Hungary.
[Fust, George] Semmelweis University, 3rd Department of Internal Medicine, Eotvos ut 12., H-1121 Budapest, Hungary.
RP Prohaszka, Z (reprint author), Semmelweis University, 3rd Department of Internal Medicine, H-1121 Budapest, Hungary.
EM prohoz@bkt.sote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 296
EP 302
PG 7
ER
PT J
AU Gyuris,
Segesdi, J
Mezei, M
Balog, K
Jelenik, Zs
Takacs, M
Berencsi, Gy
Foldes, I
Majtenyi, K
Kollar, K
Minarovits, J
AF Gyuris, Agnes
Segesdi, Judit
Mezei, Maria
Balog, Katalin
Jelenik, Zsuzsanna
Takacs, Maria
Berencsi, Gyorgy
Foldes, Istvan
Majtenyi, Katalin
Kollar, Katalin
Minarovits, Janos
TI Virological, Neurological and Histological Investigations of a Child Born to a Mother with AIDS
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; mother to child transmission; central nervous system development; delayed myelinization
ID HIV; mother to child transmission; central nervous system development; delayed myelinization
AB HIV-1 was isolated from a child at 6 and 9 months of age, proving the vertical transmission of infection from the mother with AIDS. The p24 antigen test of the plasma at 9 months of age was positive as well. A positive PCR reaction was detected in J34 cells, infected with the supernatant of the peripheral blood lymphocytes of the child. According to phenotypic characterization, the virus proved to be a SI (syncytium inducing) isolate, growing in PBL, MT2, J34 and other T and monocytic cell lines. The isolate was AZT sensitive. Two methods were applied for genotypic characterization: 1. Heteroduplex mobility assay (HMA), 2. Sequence analysis of a part of the env gene. On the basis of both of these methods, this virus belongs to the B subtype of HIV-1, which is prevalent mainly in Europe and in the USA. The neurological status of the child was followed regularly. At autopsy the presence of p24 antigen was detected in glial cells of the frontal cortex, proving the presence of the virus in the brain. A retardation of the development of the central nervous system could be observed as well.
C1 [Gyuris, Agnes] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Segesdi, Judit] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Mezei, Maria] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Balog, Katalin] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Jelenik, Zsuzsanna] St. Laszlo HospitalBudapest, Hungary.
[Takacs, Maria] Bela Johan National Institute of Hygiene, Department of VirologyBudapest, Hungary.
[Berencsi, Gyorgy] Bela Johan National Institute of Hygiene, Department of VirologyBudapest, Hungary.
[Foldes, Istvan] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Majtenyi, Katalin] Orszagos Pszichiatriai es Neurologiai Intezet, Alkohologiai OsztalyBudapest, Hungary.
[Kollar, Katalin] St. Panthaleon HospitalDunaujvaros, Hungary.
[Minarovits, Janos] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
RP Gyuris, (reprint author), Bela Johan National Institute of Hygiene, Microbiological Research Group, H-1529 Budapest, Hungary.
EM gyuris@microbi.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 303
EP 308
PG 6
ER
PT J
AU Knox, JR
Connors, AT
AF Knox, J Richard
Connors, A Tom
TI Prodrugs in Cancer Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE antibody targeting; drug targeting; gene therapy; antitumor agents
ID antibody targeting; drug targeting; gene therapy; antitumor agents
AB At present, chemotherapy is not very effective against common solid cancers especially once they have metastasised. However, laboratory experiments and studies on dose intensification in humans have indicated that some anti-cancer agents might be curative but only if the dose given was very much higher than that presently obtainable clinically. Prodrugs, activated by enzymes expressed at raised level in tumors, can deliver at least 50-fold the normal dose and can cure animals with tumors normally resistant to chemotherapy. This approach has not yet proved to be practicable clinically because of the rarity of human tumors expressing a high level of an activating enzyme. However, new therapies have been proposed overcome this limitation of prodrug therapy. Enzymes that activate prodrugs can be directed to human tumor xenografts by conjugating them to tumor associated antibodies. After allowing for the conjugate to clear from the blood a prodrug is administered which is normally inert but which is activated by the enzyme delivered to the tumor. This procedure is referred to as ADEPT (antibody-directed enzyme prodrug therapy). Early clinical trials are promising and indicate that ADEPT may become an effective treatment for all solid cancers for which tumor associated or tumor specific antibodies are known. Tumors have also been targeted with the genes encoding for a prodrug activating enzymes. This approach has been called gene-directed enzyme prodrug therapy (GDEPT) or VDEPT (virus-directed enzyme prodrug therapy) and has shown good results in animal models. These new therapies may finally realise the potential of prodrugs in cancer chemotherapy.
C1 [Knox, J Richard] Imperial College School of Medicine, Department of Medical Oncology, Charing Cross Campus, The Reynolds Building, St. Dunstan's Road, W68RP London, UK.
[Connors, A Tom] The School of Pharmacy, Centre for Polymer TherapeuticsLondon, UK.
RP Knox, JR (reprint author), Imperial College School of Medicine, Department of Medical Oncology, W68RP London, UK.
EM r.knox@cxwms.ac.uk
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 1997
VL 3
IS 4
BP 309
EP 324
PG 16
ER
PT J
AU Klein, E
AF Klein, Eva
TI The Complexity of the Epstein-Barr Virus Infection in Humans
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE EBV; infections mononucleosis; immune response
ID EBV; infections mononucleosis; immune response
AB The Epstein-Barr virus (EBV) was isolated 40 years ago from cultures of Burkitt lymphoma cells (BL). The tumor was encountered in Africa and exhibited characteristical geographical, clinical and pathological features. Serological studies revealed that the virus is ubiquitous in humans. The primary infection is often accompanied by the syndrome of acute infectious mononucleosis (IM). It can induce malignant proliferation of B lymphocytes in conditions of immunodeficiency. EBV can immortalize B lymphocytes in culture. These cells carry the virus as episomes and express 9 virally encoded proteins. Their immunological recognition constitutes the surveillance which is responsible for the healthy virus carrier state. The main virus reservoir is represented by a low number of resting B lymphocyte which contain the viral genome but do not express its transformation proteins. The viral genom is detectable in all African BLs, in variable proportions of nasopharyngeal carcinoma, Hodgkin's disease, T cell lymphoma, lymphoepithelial like carcinoma, gastric carcinoma and leiomyosarcoma cases. The role of EBV in the genesis of these tumors is unknown.
C1 [Klein, Eva] Karolinska Institutet, Microbiology and Tumor Biology Center (MTC), S-17177 Stockholm, Sweden.
RP Klein, E (reprint author), Karolinska Institutet, Microbiology and Tumor Biology Center (MTC), S-17177 Stockholm, Sweden.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 3
EP 7
PG 5
ER
PT J
AU Moldvay, J
Strausz, J
Egervary, M
Agocs, L
Bocsi, J
Schaff, Zs
AF Moldvay, Judit
Strausz, Janos
Egervary, Marta
Agocs, Laszlo
Bocsi, Jozsef
Schaff, Zsuzsa
TI P53 Expression in Stage I Squamous Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; immunohistochemistry; lung cancer; flow cytometry
ID p53; immunohistochemistry; lung cancer; flow cytometry
AB P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.
C1 [Moldvay, Judit] National Koranyi Institute of Pulmonology, Department of Bronchology, Piheno u. 1., H-1529 Budapest, Hungary.
[Strausz, Janos] National Koranyi Institute of Pulmonology, Department of Bronchology, Piheno u. 1., H-1529 Budapest, Hungary.
[Egervary, Marta] National Koranyi Institute of Pulmonology, Department of Bronchology, Piheno u. 1., H-1529 Budapest, Hungary.
[Agocs, Laszlo] Semmelweis Egyetem-Orszagos Onkologiai Intezet, Mellkassebeszeti KlinikaBudapest, Hungary.
[Bocsi, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Moldvay, J (reprint author), National Koranyi Institute of Pulmonology, Department of Bronchology, H-1529 Budapest, Hungary.
EM moldvay@toledo.koranyi.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 8
EP 13
PG 6
ER
PT J
AU Repassy, G
Forster-Horvath, Cs
Juhasz, A
Adany, R
Tamassy, A
Timar, J
AF Repassy, Gabor
Forster-Horvath, Csaba
Juhasz, Attila
Adany, Roza
Tamassy, Anna
Timar, Jozsef
TI Expression of Invasion Markers CD44v6/v3, NM23 and MMP2 in Laryngeal and Hypopharyngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE laryngeal carcinoma; CD44v3; nm23; MMP2; immunohistochemistry
ID laryngeal carcinoma; CD44v3; nm23; MMP2; immunohistochemistry
AB Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal cancer; 15 samples) were analysed by immunohistochemistry for the expression of invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The laryngeal epithelium showed CD44v6+/v3+/NM23-/MMP2- phenotype. When tumors were grouped into TNM categories the phenotype of the T2 and T3 tumors was similar, characterised by decreased CD44v3+ and lack of MMP2 expressions. Meanwhile the NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of NM23 and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no correlation with the appearence of lymph node metastasis. Comparison of the phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages, revealed characteristic differences: T2 stage laryngeal tumors showed decreased CD44v3 and occasional NM23 and MMP2 positivity, while in T3 stage these tumors were characterised by increased frequency of NM23 positivity. The phenotype of the hypopharyngeal tumors was significantly different with a high frequency of MMP2 positive cases (5/6) and NM23+/low CD44v3+ phenotype. The sharp differences in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to the differences in their invasive capacity unlike to the size of the tumors, since the T4 stage hypopharyngeal tumors had a significantly smaller size than laryngeal ones, even at lower stages.
C1 [Repassy, Gabor] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Forster-Horvath, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Juhasz, Attila] Medical University, Department of Oto-Rhino-LaryngologyDebrecen, Hungary.
[Adany, Roza] Debrecen Medical University, Department of Hygieny and EpidemiologyDebrecen, Hungary.
[Tamassy, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 14
EP 21
PG 8
ER
PT J
AU Kolesnikova, IA
Kubasova, T
Konoplyannikov, GA
Koteles, JGy
AF Kolesnikova, I Antonina
Kubasova, Tamara
Konoplyannikov, G Anatolij
Koteles, J Gyorgy
TI Cellular Alterations Upon IR-Laser (890 nm) Exposures, In Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IR-laser; gamma irradiation; abscopal cellular effects; cell membranes; cell proliferation
ID IR-laser; gamma irradiation; abscopal cellular effects; cell membranes; cell proliferation
AB Exposure of cultured cells and small animals to ionizing radiation as well as irradiation of cultured cells with He-Ne laser can cause changes in the functional condition of plasma membranes. The ionizing radiation-induced cell membrane alterations have been determined after either partial or local exposures. The aim of the present study was to reveal whether the local laser treatments cause a general, distant, so called ''abscopal'' effect measured at cellular level, when the laser treatment is intended as a stimulatory procedure. The biological effect of infrared laser (mean power of 5 Watts, 150 Hz frequency, 890 nm wavelength) was demonstrated through 3H-concanavalin A binding by blood cells of daily irradiated (altogether 10 exposures) oncological and non-oncological patients as well as by changes in the proliferation of bone marrow cells of whole body gamma-irradiated (4 Gy) rats, partially laser-treated. The lectin binding of lymphocytes of oncological, as well as ischaemic heart disease patients was increased immediately after the first laser treatment. However, it was decreased after completion of the full course. In cases of inflammatory diseases the test parameters were either unchanged or decreased as compared to their self-control values. The platelets and erythrocytes did not react in any group. Gamma irradiation caused a deep inhibition of proliferation of rat bone marrow cells. The number of fibroblast colony-forming units (CFU-F) could be increased again if the animals were partially exposed to laser. Laser irradiation of one of the femurs led to some recovery of CFU-F values in the exposed as well as unexposed femur. Thus, local infrared laser treatment induces abscopal effects on the cell membrane and cell proliferation characteristics.
C1 [Kolesnikova, I Antonina] Russian Academy of Science, Medical Radiological Research Center, 249020 Obninsk, Russian Federation.
[Kubasova, Tamara] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, H-1775 Budapest, Hungary.
[Konoplyannikov, G Anatolij] Russian Academy of Science, Medical Radiological Research Center, 249020 Obninsk, Russian Federation.
[Koteles, J Gyorgy] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, H-1775 Budapest, Hungary.
RP Kubasova, T (reprint author), Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, H-1775 Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 22
EP 26
PG 5
ER
PT J
AU Zalgeviciene, V
Zukiene, J
Grazeliene, G
Sinkeviciute, G
Didziapetriene, J
AF Zalgeviciene, Violeta
Zukiene, Janina
Grazeliene, Grazina
Sinkeviciute, Giedre
Didziapetriene, Janina
TI Embryotoxicity and Teratogenicity of Some Derivatives of Chloroethylaminophenylacetic Acid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE embryotoxiciy; terotogenicity; antitumor agents
ID embryotoxiciy; terotogenicity; antitumor agents
AB Embryotoxic and teratogenic properties of Lophenal, Phenalon, Pharanox and Pharanoxi selenate were investigated experimentally. All examined antitumour agents showed embryotoxic effects. Lophenal, Phenalon and Pharanox had teratogenic effects. By modifying the structure of Pharanox with selenium a reduction in teratogenic effect was achieved.
C1 [Zalgeviciene, Violeta] Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, Santariskiu 1, 2600 Vilnius, Lithuania.
[Zukiene, Janina] Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, Santariskiu 1, 2600 Vilnius, Lithuania.
[Grazeliene, Grazina] Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, Santariskiu 1, 2600 Vilnius, Lithuania.
[Sinkeviciute, Giedre] Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, Santariskiu 1, 2600 Vilnius, Lithuania.
[Didziapetriene, Janina] Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, Santariskiu 1, 2600 Vilnius, Lithuania.
RP Didziapetriene, J (reprint author), Faculty of Medicine of Vilnius University, Department of the Experimental Therapy of Lithuanian Oncology Center, 2600 Vilnius, Lithuania.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 27
EP 29
PG 3
ER
PT J
AU Sava, G
Gagliardi, R
Cocchietto, M
Clerici, K
Capozzi, I
Marrella, M
Alessio, E
Mestroni, G
Milanino, R
AF Sava, Gianni
Gagliardi, Renato
Cocchietto, Moreno
Clerici, Katiuscia
Capozzi, Ilaria
Marrella, Mauro
Alessio, Enzo
Mestroni, Giovanni
Milanino, Roberto
TI Comparison of the Effects of the Antimetastatic Compound ImH[trans-RuCl4(DMSO)Im] (NAMI-A) on the Arthritic Rat and on MCa Mammary Carcinoma in Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ruthenium; inflammation; tumor; metastasis; treatment
ID ruthenium; inflammation; tumor; metastasis; treatment
AB The effects of the new molecule ImH[trans-RuCl4(DMSO)Im] (NAMI-A), administered orally or intraperitoneally to adjuvant-arthritic rats or orally to mice bearing s.c. or i.m. implants of MCa mammary carcinoma, were studied. NAMI-A was not able to modify the progression of chronic inflammation in the complete Freund-adjuvant injected animals. Histology indicated a significant worsening of the inflammatory process, characterised by an increased infiltration of inflammatory cells, as well as by a remarkable deposition of connective tissue fibres around the blood vessels and alveolar walls. NAMI-A had no effect on primary i.m. implanted MCa mammary carcinoma growth and its lung metastasis formation, but significantly interfered with the cell cycle of primary tumor cells following bolus oral administration. On the contrary, NAMI-A caused a significant inhibition of lung metastasis accompanied by a dramatic deposition of connective tissue fibres around the primary tumor mass, when given as medicated food to mice implanted s.c. with MCa tumor. These data indicated that NAMI-A is well absorbed after oral administration although there is no connection between lung concentration and the antimetastatic activity. Conversely, the marked deposition of connective tissues in NAMI-A treated animals is in agreement with the reported effects of the compund on extracellular matrix and tumor blood vessels.
C1 [Sava, Gianni] Callerio Foundation, Institutes of Biological Research, via A. Fleming, 34127 Trieste, Italy.
[Gagliardi, Renato] Callerio Foundation, Institutes of Biological Research, via A. Fleming, 34127 Trieste, Italy.
[Cocchietto, Moreno] Callerio Foundation, Institutes of Biological Research, via A. Fleming, 34127 Trieste, Italy.
[Clerici, Katiuscia] Callerio Foundation, Institutes of Biological Research, via A. Fleming, 34127 Trieste, Italy.
[Capozzi, Ilaria] Callerio Foundation, Institutes of Biological Research, via A. Fleming, 34127 Trieste, Italy.
[Marrella, Mauro] University of Verona, Institute of PharmacologyVerona, Italy.
[Alessio, Enzo] University of Trieste, Department of Chemical SciencesTrieste, Italy.
[Mestroni, Giovanni] University of Trieste, Department of Chemical SciencesTrieste, Italy.
[Milanino, Roberto] University of Verona, Institute of PharmacologyVerona, Italy.
RP Sava, G (reprint author), Callerio Foundation, Institutes of Biological Research, 34127 Trieste, Italy.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 30
EP 36
PG 7
ER
PT J
AU Hermanns, B
Handt, S
Kindler, J
Fuzesi, L
AF Hermanns, Benita
Handt, Stefan
Kindler, Joachim
Fuzesi, Laszlo
TI Coronary Vasculopathy in Polycythemia Vera
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE polycythaemia vera; myocardial infarction; coronary vasculary disease; intima proliferation
ID polycythaemia vera; myocardial infarction; coronary vasculary disease; intima proliferation
AB Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.
C1 [Hermanns, Benita] Medical Faculty of the Technical University of Aachen, Department of Pathology, Pauwelsstr. 30, D-52057 Aachen, Germany.
[Handt, Stefan] Medical Faculty of the Technical University of Aachen, Department of Pathology, Pauwelsstr. 30, D-52057 Aachen, Germany.
[Kindler, Joachim] Hospital Marienhohe, Department of Internal MedicineWurselen, Germany.
[Fuzesi, Laszlo] Medical Faculty of the Technical University of Aachen, Department of Pathology, Pauwelsstr. 30, D-52057 Aachen, Germany.
RP Fuzesi, L (reprint author), Medical Faculty of the Technical University of Aachen, Department of Pathology, D-52057 Aachen, Germany.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 37
EP 39
PG 3
ER
PT J
AU Blaker, H
Dyckhoff, G
Weidauer, H
Herwart, FO
AF Blaker, Hendrik
Dyckhoff, Gerhard
Weidauer, Hagen
Herwart, F Otto
TI Carcinoid Tumor of the Middle Ear in a 28-Year-Old Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE carcinoid; tumor; pathology; diagnosis; middle-ear
ID carcinoid; tumor; pathology; diagnosis; middle-ear
AB Carcinoid tumor of the middle ear is an extremely rare condition. The origin of the tumor cells is still speculative and the closeness of relationship to adenomas of the middle ear has been a matter of discussion since the first description of this tumor entity in 1980. In this study we report a case of a 28-year-old male patient with a carcinoid tumor of the middle ear. We present the results of histomorphological, immunohistochemical and electron microscopic examinations and compare our findings to those of previously published cases.
C1 [Blaker, Hendrik] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.
[Dyckhoff, Gerhard] University of Heidelberg, Department of OtorhinolaryngologyHeidelberg, Germany.
[Weidauer, Hagen] University of Heidelberg, Department of OtorhinolaryngologyHeidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.
RP Blaker, H (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 40
EP 43
PG 4
ER
PT J
AU Ala Andrade, L
Torresan, ZR
Sales, FJ
Vicentini, R
De Souza, AG
AF Ala Andrade, Liliana
Torresan, Z Renato
Sales, FS Jose
Vicentini, Regina
De Souza, A Gustavo
TI Intravenous Leiomyomatosis of the Uterus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE uterine tumor; intravenous leiomyomatosis
ID uterine tumor; intravenous leiomyomatosis
AB Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called ''benign metastasizing leiomyoma'' and ''intracaval mass and cardiac extension''. The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.
C1 [Ala Andrade, Liliana] UNICAMP - University of Campinas, School of Medicine, Department of Pathology, 13083-970 Campinas, SP, Brazil.
[Torresan, Z Renato] Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, UNICAMP, Department of GynecologyCampinas, Brazil.
[Sales, FS Jose] Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, UNICAMP, Department of GynecologyCampinas, Brazil.
[Vicentini, Regina] Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, UNICAMP, Department of GynecologyCampinas, Brazil.
[De Souza, A Gustavo] Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, UNICAMP, Department of GynecologyCampinas, Brazil.
RP Ala Andrade, L (reprint author), UNICAMP - University of Campinas, School of Medicine, Department of Pathology, 13083-970 Campinas, Brazil.
EM anatpat@turing.unicamp.br
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 44
EP 47
PG 4
ER
PT J
AU Toth, Z
Sipos, J
AF Toth, Zoltan
Sipos, Jozsef
TI Biclonal primary plasma cell leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE primary plasma cell leukemia; biclonality; immunohistology; image cytometry
ID primary plasma cell leukemia; biclonality; immunohistology; image cytometry
AB Authors present a multiparameter pathological study in a case of rapid biclonal primary plasma cell leukemia. The immunohistochemical data revealed aberrant phenotypes (monocyte, epithelial and T-cell) probably in connection with microenvironmental influences. Biclonality can be attributed to class switching during malignant transformation. Static image cytometry showed aneuploidy. The blasts of this process are active immunoregulatory cells.
C1 [Toth, Zoltan] County Hospital of Zala, Department of Pathology, Zrinyi ut 1., H-8901 Zalaegerszeg, Hungary.
[Sipos, Jozsef] County Hospital of Zala, Department of Pathology, Zrinyi ut 1., H-8901 Zalaegerszeg, Hungary.
RP Toth, Z (reprint author), County Hospital of Zala, Department of Pathology, H-8901 Zalaegerszeg, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 48
EP 51
PG 4
ER
PT J
AU Segesdi, J
Gyuris,
Banhegyi, D
Vodros, D
Bakos,
Minarovits, J
AF Segesdi, Judit
Gyuris, Agnes
Banhegyi, Denes
Vodros, Dalma
Bakos, Agnes
Minarovits, Janos
TI Plasma HIV-1 Load and Disease Progression in HIV-Infected Patients in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE plasma HIV-1 RNA copy number; NASBA; AIDS; AIDS Related Complex
ID plasma HIV-1 RNA copy number; NASBA; AIDS; AIDS Related Complex
AB Nucleic Acid Sequence Based Amplification (NASBA) is a suitable method for the quantification of HIV-1 RNA in plasma and serum samples. Since determination of the viral load appears to be a valuable marker for the prediction of disease progression and for monitoring the efficiency of antiretroviral therapy, the National AIDS Committee initiated the introduction of NASBA in Hungary at the end of 1996. We obtained plasma samples from patients with ARC and AIDS of the Szt. Laszlo Hospital, Budapest. We found an increased viral burden in untreated AIDS (CDC group C) patients compared to untreated ARC (CDC group B) patients. In plasma samples of clinically stable ARC and AIDS patients treated with antiretroviral drugs we detected relatively low HIV-1 RNA copy levels while similarly treated ARC and AIDS patients with progressive disease had high HIV-1 RNA copy numbers. The CD4+ T-cell count was lower in AIDS patients compared to ARC patients, as expected. In general, there was an inverse correlation (r = -0.487, P < 0.0001) between CD4+ T-cell counts and HIV-1 RNA levels. We concluded that measurement of HIV-1 RNA plasma level has an important role in assessing prognosis and effects of antiretroviral therapy in HIV-infected patients.
C1 [Segesdi, Judit] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Gyuris, Agnes] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Banhegyi, Denes] St. Istvan and St Laszlo Hospital, Immunology LaboratoryBudapest, Hungary.
[Vodros, Dalma] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Bakos, Agnes] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
[Minarovits, Janos] Bela Johan National Institute of Hygiene, Microbiological Research Group, Piheno ut 1., H-1529 Budapest, Hungary.
RP Segesdi, J (reprint author), Bela Johan National Institute of Hygiene, Microbiological Research Group, H-1529 Budapest, Hungary.
EM sgesdi@microbi.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 52
EP 55
PG 4
ER
PT J
AU Marodi, LCs
Csiszar, A
Sierra-Vazquez, B
Di Luca, D
Barabas,
Nagy, K
Ongradi, J
AF Marodi, Laszlo Csaba
Csiszar, Anna
Sierra-Vazquez, Beatriz
Di Luca, Dario
Barabas, Eva
Nagy, Karoly
Ongradi, Joseph
TI Studies on the Antibodies to Human Herpesvirus Type 6 Among Hungarian Patients with Asymptomatic HIV Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HHV-6; seroepidemiology; IgM; IgG avidity; asymptomatic HIV-1 infection
ID HHV-6; seroepidemiology; IgM; IgG avidity; asymptomatic HIV-1 infection
AB The occurrence and the possible role in promoting HIV infection by human herpesvirus type 6 (HHV-6) have not yet been revealed in Hungary. In different groups of patients, serum titre of IgM and IgG antibodies, as well as avidity of IgG were quantitated by indirect immunofluorescence and an enzyme-linked immunosorbent assay, using isolate U1102 of HHV-6 variant A as antigen. In 60% of HIV-seronegative adult controls, high avidity IgG antibodies were found in low titre suggesting childhood infection. In HIV-seronegative persons with high risk behaviour for HIV-infection, both IgM and low avidity IgG were frequently found in higher titre, representing either primary or frequent reinfections, or reactivation of latent HHV-6. In asymptomatic HIV-seropositive patients, high titre of high avidity IgG antibodies was predominant, proving virus infection in the near past. These results indicate the contribution of HHV-6 to immunosuppression prior to AIDS, predisposing the organism to HIV infection.
C1 [Marodi, Laszlo Csaba] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
[Csiszar, Anna] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
[Sierra-Vazquez, Beatriz] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
[Di Luca, Dario] University of Ferrara, Institute of MicrobiologyFerrara, Italy.
[Barabas, Eva] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Nagy, Karoly] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Ongradi, Joseph] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
RP Ongradi, J (reprint author), Semmelweis University, Department of Medical Microbiology, Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 56
EP 61
PG 6
ER
PT J
AU Paku, S
AF Paku, Sandor
TI Current Concepts of Tumor-Induced Angiogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE tumor; metastasis; angiogenesis; morphology
ID tumor; metastasis; angiogenesis; morphology
AB Tumor induced angiogenesis is responsible for the nutrition of the growing tumor and can also increase the probability of hematogenous tumor dissemination. Data obtained from morphological analysis of tumor angiogenesis can contribute to the development of new anti-angiogenic therapies. Based on in vitro and in vivo observations several models of angiogenesis were introduced, explaining the mechanism of lumen formation and the timing of basement membrane depositon. (1) Lumen is formed either by cell body curving or by fusion of intracellular vacuoles of nonpolarized endothelial cells. New basement membrane is deposited after lumen formation. (2) Slit-like lumen is immediately formed by migrating polarized endothelial cells. Basement membrane is continuously deposited during endothelial cell migration, only cellular processes of the endothelial cell migrating on the tip of the growing capillary are free of deposited basement membrane material. (3) Development of transluminal bridges in larger vessels - a process called intussusceptive growth - leads to the division of the vessels. These models, however, describe angiogenesis in tissues rich in connective tissue. Different processes of angiogenesis take place in organs - such as liver, lungs, adrenals, which are the most frequent sites of metastasis - having high vessel density without sufficient space for capillary sprouting. In the case of liver metastases of Lewis lung carcinoma the proliferation of endothelial cells was elicited only by direct contact between tumor and endothelial cells, leading to the development of large convoluted vessels inside the metastases. These vessels were continuous with the sinusoidal system, suggesting that these metastases have dual blood supply. This observation, among others, is in contrast to the generally accepted view that liver tumors have arterial blood supply. The increasing number of data demonstrating the dual or venous blood supply of liver metastases should be taken into consideration in the therapy of liver metastasis.
C1 [Paku, Sandor] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Paku, S (reprint author), Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, H-1085 Budapest, Hungary.
EM paku@korb1.sote.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1998
VL 4
IS 1
BP 62
EP 75
PG 14
ER
PT J
AU Ross, JP
Rao, Sh
Cunningham, D
AF Ross, J Paul
Rao, Sheela
Cunningham, David
TI Chemotherapy of Oesophago-Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE oesophagus; gastric; chemotherapy; chemoradiation
ID oesophagus; gastric; chemotherapy; chemoradiation
AB Oesophageal and gastric cancers are common tumors that represent a number of challenges for oncologists, gastroenterologists and surgeons. The prognosis remains poor with the majority of patients presenting with advanced disease. Combined chemotherapy and radiotherapy has demonstrated a survival benefit in patients with loco-regional oesophageal cancer compared to radiotherapy alone. In an interim analysis we have observed a 62% response rate using a chemoradiation regimen based on protracted venous infusion of 5-fluorouracil and cisplatin combined with radiotherapy in patients with inoperable oesophageal cancer. Improved outcomes with loco-regional disease has rekindled interest in preoperative therapy. In a trial comparing preoperative chemoradiation to surgery alone in patients with operable oesophageal adenocarcinoma, survival was improved with multimodality treatment. In addition, a study including both adeno- and squamous carcinomas demonstrated a trend towards improved survival. A complete pathological response to chemoradiation was associated with significantly improved survival. Gastric cancer is one of the most chemosensitive solid tumors of the gastrointestinal tract with the majority of patients being suitable for palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of the Royal Marsden Hospital and first reported in 1991. In a prospective randomised trial including 274 patients ECF has been compared with the standard combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients with previously untreated gastric cancer. Overall response rate, failure-free and overall survival were significantly improved with ECE, ECF also demonstrated improved quality of life and cost effectiveness when compared to the FAMTX regimen. ECF should now be regarded as the standard treatment for advanced oesophago-gastric cancer against which new therapies should be compared. In addition the Medical Research Council are conducting a trial randomising patients between surgery alone and perioperative chemotherapy using the ECF regimen in operable gastric cancer.
C1 [Ross, J Paul] The Royal Marsden Hospital, Department of Medicine and the Gastrointestinal Unit, Downs Road, SM2 5PT Sutton, Surrey, UK.
[Rao, Sheela] The Royal Marsden Hospital, Department of Medicine and the Gastrointestinal Unit, Downs Road, SM2 5PT Sutton, Surrey, UK.
[Cunningham, David] The Royal Marsden Hospital, Department of Medicine and the Gastrointestinal Unit, Downs Road, SM2 5PT Sutton, Surrey, UK.
RP Cunningham, D (reprint author), The Royal Marsden Hospital, Department of Medicine and the Gastrointestinal Unit, SM2 5PT Sutton, UK.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 87
EP 95
PG 9
ER
PT J
AU Petty, DR
Evans, TA
Duncan, DI
Kurbacher, MCh
Cree, AI
AF Petty, D Russel
Evans, T Alan
Duncan, D Iain
Kurbacher, M Christian
Cree, A Ian
TI Drug Resistance in Ovarian Cancer - the Role of p53
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ovary; adenocarcinoma; p53; immunostaining; bcl-2; chemotherapy
ID ovary; adenocarcinoma; p53; immunostaining; bcl-2; chemotherapy
AB The aims were to determine the importance of p53 and bcl-2 expression on the response to chemotherapy with alkylating agents in patients with ovarian cancer. We have followed the response to chemotherapy in a series of 59 patients with ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors. Patients were grouped according to their response to chemotherapy (stable or progressive disease) assessed at 6, 12, and 18 months. There was increasing divergence of p53+ and p53- tumors over time. Of those which were p53+, 25% showed progression at 6 months, 80% at 12 months and 89% progression at 18 months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6 , 12 and 18 months respectively. For bcl-2, in 23/55 positive tumors there was progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative tumors at 6, 12 and 18 months respectively. Those tumors which were bcl-2 and p53 negative were most likely to progress, while those which were bcl-2 and p53 positive had the best prognosis. These differences did not translate into increased overall survival with minimum follow-up of 12 months. This data lends support to our suggestion that despite initially increased susceptibility to alkylating agents, enhanced genomic instability due to p53 inactivation may render tumors more likely to develop resistance to chemotherapy over time. This effect may be altered by bcl-2 function, lack of which will lead to a good response to chemotherapy as the tumor's ability to undergo apoptosis will not be compromised.
C1 [Petty, D Russel] Ninewells Hospital and Medical School, Department of Obstetrics and GynaecologyDundee, Scotland, UK.
[Evans, T Alan] Ninewells Hospital and Medical School, Department of PathologyDundee, Scotland, UK.
[Duncan, D Iain] Ninewells Hospital and Medical School, Department of Obstetrics and GynaecologyDundee, Scotland, UK.
[Kurbacher, M Christian] University of Cologne Medical Center, Labor fur Chemosensitivitatestungen Universitats & FrauenklinikCologne, Germany.
[Cree, A Ian] University College London, Institute of Ophthalmology, Department of Pathology, Bath Street, EC1V9EL London, UK.
RP Cree, AI (reprint author), University College London, Institute of Ophthalmology, Department of Pathology, EC1V9EL London, UK.
EM i.cree@ucl.ac.uk
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 97
EP 102
PG 6
ER
PT J
AU Athanassiadou, P
Sakellariou, V
Petrakakou, E
Athanassiades, P
Zerva, Ch
Liossi, A
Michalas, S
AF Athanassiadou, Pauline
Sakellariou, Vasiliki
Petrakakou, Efthalia
Athanassiades, Peter
Zerva, Cherry
Liossi, Anna
Michalas, Stylianos
TI Cathepsin-D Immunoreactivity in Ovarian Cancer: Correlation with Prognostic Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ovarian carcinoma; cathepsin D; immunocytochemistry; prognostic factors
ID ovarian carcinoma; cathepsin D; immunocytochemistry; prognostic factors
AB In view of the somewhat inconclusive nature of the reports of the role of Cathepsin D (Cath D) in ovarian carcinoma and its relationship with various other parameters of malignancy the present study was performed to aid in the further clarification of this role. One hundred freshly resected primary ovarian carcinomas of various histological types were studied for ER, PR and Cath D status and the results examined with respect to menopausal status, histology, size and lymph node invasion. In our series Cath D positivity was more frequent in serous than in other types of ovarian cancer but this Cath D positivity was not related to the frequency of lymph node invasion regardless of the size of the tumor. Nor was any association observed between Cath D positivity and ER or PR status of the tumors or the menopausal state of the patients. The reported prognostic value of Cath D, ER and PR is discussed as well as the distinction between tumor invasion by lymphatic channels and direct interstitial infiltration. It was concluded that Cath D may not play a role in the former mode but, as might be expected from its proteolytic properties, in local spread by means of tissue destruction.
C1 [Athanassiadou, Pauline] Alexandra Hospital Medical School, Athens University, Department of Cytology, 75 Micras Asias Str, GR-11527 Athens, Greece.
[Sakellariou, Vasiliki] Alexandra Hospital Medical School, Athens University, 1st Obstetrics ClinicAthens, Greece.
[Petrakakou, Efthalia] Alexandra Hospital Medical School, Athens University, Department of Cytology, 75 Micras Asias Str, GR-11527 Athens, Greece.
[Athanassiades, Peter] University of Athens, Alexandra Hospital, Clinical TherapeuticsAthens, Greece.
[Zerva, Cherry] University of Athens, Alexandra Hospital, Clinical TherapeuticsAthens, Greece.
[Liossi, Anna] Alexandra Hospital Medical School, Athens University, Department of Cytology, 75 Micras Asias Str, GR-11527 Athens, Greece.
[Michalas, Stylianos] Alexandra Hospital Medical School, Athens University, 1st Obstetrics ClinicAthens, Greece.
RP Athanassiadou, P (reprint author), Alexandra Hospital Medical School, Athens University, Department of Cytology, GR-11527 Athens, Greece.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 103
EP 107
PG 5
ER
PT J
AU Ladanyi, A
Nagy, OJ
Jeney, A
Timar, J
AF Ladanyi, Andrea
Nagy, O Julianna
Jeney, Andras
Timar, Jozsef
TI Cytokine Sensitivity of Metastatic Human Melanoma Cell Lines - Simultaneous Inhibition of Proliferation and Enhancement of Gelatinase Activity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE melanoma; cytokines; proliferation; metalloproteinases
ID melanoma; cytokines; proliferation; metalloproteinases
AB The effect of a panel of cytokines on the proliferation and type IV collagenase production was studied in four melanoma cell lines of different origin, tumorigenicity and metastatic capacity. TGF-?, TNF-? and to a lesser extent, IL-1? exhibited antiproliferative effect on the cell lines, with some lines showing varying degree of resistance. The sensitivity did not correlate directly with the origin or the biological behavior of the tumor lines, suggesting that cytokine resistance of advanced stage melanoma cells may be relative. IL-2, IL-10 and IL-12 displayed little or no effect on proliferation. The effect of cytokines on metalloproteinase production showed a cell line dependent pattern. Interestingly, those cytokines that exhibited the most pronounced antiproliferative activity, also proved most effective in stimulating collagenase secretion, often simultaneously, in the same line. The results indicate that pleiotropic cytokines can have positive and negative effects simultaneously on various steps of tumor progression.
C1 [Ladanyi, Andrea] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi ut 26., H-1085 Budapest, Hungary.
[Nagy, O Julianna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Ladanyi, A (reprint author), Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, H-1085 Budapest, Hungary.
EM ladanyi@korb1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 108
EP 114
PG 7
ER
PT J
AU Grover-McKay, M
Walsh, AS
Seftor, AE
Thomas, AP
Hendrix, JM
AF Grover-McKay, Maleah
Walsh, A Susan
Seftor, A Elisabeth
Thomas, A Patricia
Hendrix, JC Mary
TI Role for Glucose Transporter 1 Protein in Human Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; invasion; GLUT expression
ID breast cancer; invasion; GLUT expression
AB Glycolysis is increased in cancer cells compared with normal cells. It has been shown that glucose enters cells via a family of five functional glucose transporters (GLUT). However, GLUT expression appears to be altered in human breast cancer, which may serve as a selective advantage and facilitate the metastatic potential of these cells. The relationship of GLUT isoform expression and breast cancer cell invasiveness has not been adequately addressed. Thus, the purpose of this study was to investigate whether an association exists between GLUT expression and human breast cancer cell invasiveness. Invasiveness of the human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using an in vitro assay and compared with cellular GLUT isoform expression, assessed by Western blot analysis and verified by immunohistochemistry in a poorly differentiated human ductal breast cancer. Cell surface GLUT-1 expression was associated with the invasive ability of MCF-7 (2.0 + 0.02%), MDA-MB-435 (6.4 + 0.4%), and MDA-MB-231 (19.3 + 2.0%). However, GLUT-2 and GLUT-5 were inversely associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was undetected. In a poorly differentiated human ductal breast cancer, in situ GLUT-1 staining was intense. GLUT-1 expression was associated with the in vitro invasive ability of human breast cancer cells which was validated in situ. If this relationship is found to exist in a larger number of human breast cancer tissues, it may be possible to develop diagnostic and therapeutic strategies based on targeted GLUT isoform expression.
C1 [Grover-McKay, Maleah] University of Iowa College of Medicine and University of Iowa Cancer Center, Departments of Radiology, Internal Medicine, IA52242 Iowa City, Iowa, USA.
[Walsh, A Susan] University of Iowa College of Medicine and University of Iowa Cancer Center, Departments of Radiology, Internal Medicine, IA52242 Iowa City, Iowa, USA.
[Seftor, A Elisabeth] University of Iowa, Department of AnatomyIowa City, USA.
[Thomas, A Patricia] University of Kansas Medical School, Department of PathologyKansas City, USA.
[Hendrix, JC Mary] University of Iowa, Department of AnatomyIowa City, USA.
RP Grover-McKay, M (reprint author), University of Iowa College of Medicine and University of Iowa Cancer Center, Departments of Radiology, Internal Medicine, IA52242 Iowa City, USA.
EM maleah-grover@uiowa.edu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 115
EP 120
PG 6
ER
PT J
AU Bencsath, M
Paloczi, K
Szalai, Cs
Szenthe, A
Szeberenyi, J
Falus, A
AF Bencsath, Marta
Paloczi, Katalin
Szalai, Csaba
Szenthe, Andrea
Szeberenyi, Julia
Falus, Andras
TI Histidine Decarboxylase in Peripheral Lymphocytes of Healthy Individuals and Chronic Lymphoid Leukemia Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE histamine; lymphocyte; cell proliferation; leukemia
ID histamine; lymphocyte; cell proliferation; leukemia
AB Histidine decarboxylase (HDC), the only enzyme capable of synthetizing histamine, has been found in many proliferating cells and tissues suggesting a role of histamine in cellular proliferation. In this study expression of HDC and the significance of histamine in the proliferation of peripheral lymphocytes of five healthy persons and six patients with chronic lymphoid leukemia (CLL) was examined. Expression of HDC mRNA and the protein was proved by reverse transcriptase polymerase chain reaction and by immunoblot, respectively. The role of histamine was studied in proliferation assays by the action of irreversible HDC inhibitor (alpha-fluoromethylhistidine--aFMH) and also by competing for the intracellular binding sites of histamine using N,N-diethyl-2,4-phenylmethyl-phenoxy-ethanamine-HCl (DPPE). Inhibiting the HDC enzyme activity by aFMH and blocking the intracellular action of histamine by DPPE, a significant decrease in cell proliferation was observed in mitogen stimulated lymphocytes of healthy donors. In CLL patients the proliferation of leukemic lymphocytes was inhibited significantly by DPPE. aFMH inhibited only the de novo histamine formation but did not the proliferation. The observations suggest that HDC has functional relevance in lymphocytes, since mitogen induced lymphocyte proliferation of healthy donors is mainly enhanced by de novo synthesis and subsequent action of intracellular histamine. Alternatively, in constitutively proliferating chronic lymphoid leukemia cells we suggest that the preformed pool but not the de novo synthesized intracellular histamine interferes with cellular proliferation.
C1 [Bencsath, Marta] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4., H-1089 Budapest, Hungary.
[Paloczi, Katalin] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Szalai, Csaba] Heim Pal Children's HospitalBudapest, Hungary.
[Szenthe, Andrea] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4., H-1089 Budapest, Hungary.
[Szeberenyi, Julia] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4., H-1089 Budapest, Hungary.
[Falus, Andras] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4., H-1089 Budapest, Hungary.
RP Falus, A (reprint author), Semmelweis University, Department of Genetics, Cell and Immunobiology, H-1089 Budapest, Hungary.
EM faland@net.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 121
EP 124
PG 4
ER
PT J
AU Toth, E
Lazar, I
Selmeczi, D
Marx, G
AF Toth, Esther
Lazar, Istvan
Selmeczi, David
Marx, George
TI Lower Cancer Risk in Medium High Radon
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer risk; radon
ID cancer risk; radon
AB Radon exposure was shown to be carcinogenic and suggested as a possible causative factor for lung cancer in man. A hypothesis is introduced that medium high radon (between 110 and 165 Bq/m3) causes lower cancer risk among women younger than 61 years, independent of the type of cancer. The presented results verify this statement with a probability of not less than 98%.
C1 [Toth, Esther] RAD Lauder Laboratory, Budakeszi ut 48., H-1121 Budapest, Hungary.
[Lazar, Istvan] RAD Lauder Laboratory, Budakeszi ut 48., H-1121 Budapest, Hungary.
[Selmeczi, David] RAD Lauder Laboratory, Budakeszi ut 48., H-1121 Budapest, Hungary.
[Marx, George] Eotvos University, Atomic Physics DepartmentBudapest, Hungary.
RP Toth, E (reprint author), RAD Lauder Laboratory, H-1121 Budapest, Hungary.
EM et@rad.lauder.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 125
EP 129
PG 5
ER
PT J
AU Cserny, G
AF Cserny, Gabor
TI Proliferative Epithelial Changes in Ectopic Gastric Mucosa of Meckel's Diverticula
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Meckel's diverticulum; ectopic gastric mucosa; reflux gastritis; dysplasia; hyperplasia; p53; Ki-67
ID Meckel's diverticulum; ectopic gastric mucosa; reflux gastritis; dysplasia; hyperplasia; p53; Ki-67
AB Twenty-one Meckel's diverticula containing an adequate amount of assessable heterotopic gastric mucosa were investigated for epithelial changes. Marked or moderate foveolar hyperplasia was present in 52% and 29% of the cases, respectively. Four cases displayed an excessive epithelial proliferation indefinite for dysplasia. It is pointed out that reflux type gastritis or gastropathy, which is the most common lesion in the ectopic gastric mucosa of Meckel's diverticulum, can be associated with the same confusing epithelial proliferation as reflux gastritis in the stomach, but these lesions are best regarded as representing atypia of repair. Distinguishing features from dysplasia are maturation towards the surface, lack of hyperchromatism and abscence of atypical mitoses. Negative p53 immunostaining and localization of the Ki-67 positivity to the expanded neck region could be additive clues that can help to classify lesions indefinite for dysplasia as negative for dysplasia. On the basis of the similarities of the ectopic and ortotopic gastric mucosa, it is suggested that these additive clues previously used in other parts of the digestive tract could also apply for the stomach.
C1 [Cserny, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserny, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 130
EP 134
PG 5
ER
PT J
AU Rice, LR
Tang, GD
Taylor, DJ
AF Rice, L Renee
Tang, G Dean
Taylor, D John
TI Actin Cleavage in Various Tumor Cells is not a Critical requirement for executing apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE actin cleavage; apoptosis; caspase
ID actin cleavage; apoptosis; caspase
AB Actin is a major cytoskeletal protein which is involved in many physiological cellular functions such as motility, cell shape, and adhesion. Recently, actin has also been reported to be cleaved by apoptotic proteases (i.e., caspases) and this cleavage is thought to contribute to the apoptotic process. However, conflicting data also exists as to whether actin represents a true caspase substrate during apoptosis induction in vivo (i.e., inside the cells). In this study, we critically examined the actin cleavage patterns during apoptosis of several tumor cell lines derived from three different species (i.e., mouse, rat, and human). Our findings demonstrate that: 1) actin cleavage in vivo is not a common phenomenon since apoptosis caused by multiple inducers in most cell types examined occurs without evidence of actin degradation; and 2) in certain cell types (e.g., U937), spontaneous, actin cleavage is observed which is not prevented by various specific chemical/peptide inhibitors of proteases such as caspases or serine proteases although apoptosis per se is retarded by some of these inhibitors. Our results conclude that actin is not a critical substrate for apoptotic proteases in vivo during apoptosis.
C1 [Rice, L Renee] Wayne State University, Biological Sciences Department, 2105 Biological Science Bldg., 48202 Detroit, MI, USA.
[Tang, G Dean] Wayne State University, Department of Radiation OncologyDetroit, USA.
[Taylor, D John] Wayne State University, Biological Sciences Department, 2105 Biological Science Bldg., 48202 Detroit, MI, USA.
RP Taylor, DJ (reprint author), Wayne State University, Biological Sciences Department, 48202 Detroit, USA.
EM cheyenne@sun.science.wayne.edu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 135
EP 145
PG 11
ER
PT J
AU Zalatnai, A
Zala, J
Sandor, G
AF Zalatnai, Attila
Zala, Judit
Sandor, Gabor
TI Coccidioidomycosis in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE coccidioidomycosis; skin; pathology; human
ID coccidioidomycosis; skin; pathology; human
AB A case of an isolated subcutaneous coccidioidomycosis in a 61-year-old man is presented. The patient has lived and worked in Arizona for 3 years previously but developed no apparent clinical signs of the disease. The painless, cavitating, tumor-like mass was surgically excised and the diagnosis was established by histological demonstration of the fungi and confirmed by serum counterimmunoelectrophoresis. This represents the first imported case of coccidioidomycosis in Hungary.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Zala, Judit] Bela Johan National Center for Epidemiology, Mycological DepartmentBudapest, Hungary.
[Sandor, Gabor] Central European UniversityBudapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 147
EP 151
PG 6
ER
PT J
AU Schmitz, G
Aslanidis, Ch
Lackner, JK
AF Schmitz, Gerd
Aslanidis, Charalampos
Lackner, J Karl
TI Recent Advances in Molecular Genetics of Cardiovascular Disorders - Implications for Atherosclerosis and Diseases of Cellular Lipid Metabolism
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE cardiovascular disease; risk assessment; atherosclerosis; thrombosis; hemostasis; hypertension; obesity; lipoproteins; molecular genetics
ID cardiovascular disease; risk assessment; atherosclerosis; thrombosis; hemostasis; hypertension; obesity; lipoproteins; molecular genetics
AB Two developments in molecular genetics will profoundly influence our understanding and the diagnosis of cardiovascular disorders. First, the identification of genes responsible for monogenic and polygenic traits by analysis of e.g. large pedigrees and affected sib pairs provides invaluable data regarding the role of specific genes in common diseases like arteriosclerosis, hypertension, diabetes, thrombosis/hemostasis and obesity. Besides the insights into the underlying pathophysiology, this knowledge will permit to identify persons at high risk for disease development. These patients can then obtain a targeted intervention. The second development is related to the availability of new analytical tools for molecular biology. New methods such as sequencing by hybridisation (SBH), DNA-array technology or matrix assisted laser desorption/ionisation-time of flight mass spectroscopy (MALDI-TOF) permit sequence analysis of complete genes within hours. Automated PCR-technologies with homogenous amplicon detection formats simplify PCR and permit its use in the routine laboratory setting. Considering cardiovascular diseases there is a number of genes involved in lipid metabolism (apolipoproteins, lipoprotein receptors, lipolytic enzymes), thrombosis/hemostasis (platelet receptors, pro- and anticoagulant proteins, fibrinogen, PAI's), hypertension (angiotensin converting enzyme, angiotensinogen) glucose metabolism (glucose transporters, enzymes) and obesity (hormones, receptors), that are interesting candidates for sophisticated genetic risk assessment. Furthermore, there are also gene candidates involved in processes of early atherogenesis and chronic inflammation such as complement proteins, cell adhesion molecules, and cellular receptors and enzymes. Most of these gene candidates were derived from pathophysiologic knowledge and subsequent epidemiological studies. However, it is foreseeable that in the coming years genes will be identified which were not known so far to be involved in cardiovascular diseases. Genetic studies will be of prime importance in this area, as is exemplified by animal models. In the long term, analysis of these candidate genes before the implementation of therapy will permit a targeted intervention approach towards high risk patients. This will reduce the overall costs of health care without reducing the quality.
C1 [Schmitz, Gerd] University of Regensburg, Institute for Clinical Chemistry and Laboratory Medicine, D-93042 Regensburg, Germany.
[Aslanidis, Charalampos] University of Regensburg, Institute for Clinical Chemistry and Laboratory Medicine, D-93042 Regensburg, Germany.
[Lackner, J Karl] University of Regensburg, Institute for Clinical Chemistry and Laboratory Medicine, D-93042 Regensburg, Germany.
RP Schmitz, G (reprint author), University of Regensburg, Institute for Clinical Chemistry and Laboratory Medicine, D-93042 Regensburg, Germany.
EM Gerd.Schmitz@klinik.uni-regensburg.de
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1998
VL 4
IS 2
BP 152
EP 160
PG 9
ER
PT J
AU Canal, P
Gamelin, E
Vassal, G
Robert, J
AF Canal, Pierre
Gamelin, Erick
Vassal, Gilles
Robert, Jacques
TI Benefits of Pharmacological Knowledge in the Design and Monitoring of Cancer Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE anticancer drugs; pharmacokinetics; pharmacodynamics; dose adaptation; chemotherapy
ID anticancer drugs; pharmacokinetics; pharmacodynamics; dose adaptation; chemotherapy
AB Prescribing chemotherapy is a difficult task, because of drug resistance, which prevents all tumors to respond to a given protocol and because of drug toxicity, which is generally unavoidable but which must be limited to acceptable levels. The therapeutic window of anticancer drugs is very narrow and clinicians have to try to optimize the individual doses and schedules of the drugs to be administered. They can rely upon simple anthropometric features, such as body weight or surface area; they can also take into account the physiological status of the patient : age, liver and kidney function, genetic characteristics of drug metabolism, etc. The best way for dose adaptation lies in the establishment of pharmacokinetic/pharmacodynamic relationships, i.e., between the behavior of a drug in the body and its efficacy and toxicity. When it is established that the optimal effect of a drug is related to a given parameter, such as the area under the curve plotting plasma concentration vs. time (AUC), it becomes possible to administer the drug with the dose allowing to obtain the target parameter value. Individual dose adaptation can be achieved thanks to the study of the pharmacokinetics of a test dose preceding that of the therapeutic dose, or by the measure of drug plasma levels, either at steady state during a protracted infusion, or from cycle to cycle during repetitive protocols. Population analysis now allows the adaptation of anticancer drug dosing from a minimum knowledge of individual pharmacokinetic features, together with other characteristics of the patients such as age, gender or physiological functions.
C1 [Canal, Pierre] Centre Claudius-Regaud, 20 rue du Pont-Saint-Pierre, 31052 Toulouse, France.
[Gamelin, Erick] Centre Paul-Papin, 2 rue Moll, 49033 Angers, France.
[Vassal, Gilles] Institute Gustave Roussy, rue Camille-Desmoulins, 94805 Villejuif, France.
[Robert, Jacques] Institut Bergonie, Laboratoire de Biochimie et Pharmacologie, 180 rue de Saint-Genes, 33076 Bordeaux, France.
RP Robert, J (reprint author), Institut Bergonie, Laboratoire de Biochimie et Pharmacologie, 33076 Bordeaux, France.
EM robert@bergonie.org
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 171
EP 178
PG 8
ER
PT J
AU Tang, GD
Li, L
Zhu, Z
Joshi, B
Johnson, RC
Marnett, JL
Honn, VK
Crissman, DJ
Krajewski, S
Reed, CJ
Timar, J
Porter, TA
AF Tang, G Dean
Li, Li
Zhu, Zhenyu
Joshi, Bindu
Johnson, R Carl
Marnett, J Lawrence
Honn, V Kenneth
Crissman, D John
Krajewski, Stanislaw
Reed, C John
Timar, Jozsef
Porter, T Arthur
TI BMD188, A Novel Hydroxamic Acid Compound, Demonstrates Potent Anti-Prostate Cancer Effects in vitro and in vivo by Inducing Apoptosis: Requirements for Mitochondria, Reactive Oxygen Species, and Proteases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hydroxamic acid; prostate cancer; apoptosis; free radical; mitochondria; chemotherapy
ID hydroxamic acid; prostate cancer; apoptosis; free radical; mitochondria; chemotherapy
AB A newly synthesized cyclic hydroxamic acid compound, BMD188 [cis-1-hydroxy-4-(1-naphthyl)-6-octylpiperidine-2-one], was found to induce the apoptotic death of cultured prostate cancer cells by activating caspase-3. Orally administered BMD188 significantly inhibited the primary growth of prostate cancer cells (Du145) orthotopically implanted into SCID mice. Mechanistic studies indicated that BMD188 did not alter the protein levels of several Bcl-2 family members. In contrast, the BMD188 effect required three essential factors: reactive oxygen species (ROS), the mitochondrial respiratory chain function, and proteases. First, the apoptosis-inducing effect of BMD188 could be blocked by ROS scavengers such as Desferal. Second, both BMD188-induced PARP cleavage as well as PC3 cell apoptosis could be dramatically inhibited by several complex-specific mitochondrial respiration blockers. The involvement of mitochondria was also supported by the observations that BMD188 dramatically altered the mitochondrial distribution and morphology without affecting the cellular ATP levels. Finally, the apoptosis-inducing effect of BMD188 in PC3 cells could be significantly inhibited by serine protease inhibitors (TPCK and TLCK) as well as by caspase inhibitors (zVAD-fmk and DEVD-CHO). Collectively, the present study suggests that BMD188 and its analogs may find clinical applications in the treatment of prostate cancer patients by inducing apoptotic death of prostate cancer cells.
C1 [Tang, G Dean] Wayne State University, Biomide LaboratoriesDetroit, USA.
[Li, Li] Wayne State University, Biomide LaboratoriesDetroit, USA.
[Zhu, Zhenyu] Wayne State University, Biomide LaboratoriesDetroit, USA.
[Joshi, Bindu] Wayne State University, Biomide LaboratoriesDetroit, USA.
[Johnson, R Carl] Wayne State University, Department of ChemistryDetroit, USA.
[Marnett, J Lawrence] Vanderbilt University Medical Center, Department of BiochemistryNashville, USA.
[Honn, V Kenneth] Wayne State University, Department of Radiation Oncology, 407 Life Science Bldg., 48202 Detroit, MI, USA.
[Crissman, D John] Detroit Medical Center, Barbara Ann Karmanos Cancer InstituteDetroit, USA.
[Krajewski, Stanislaw] The Burham Institute, Apoptosis & Cell Death ProgramLa Jolla, USA.
[Reed, C John] The Burham Institute, Apoptosis & Cell Death ProgramLa Jolla, USA.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Porter, T Arthur] Wayne State University, Department of Radiation Oncology, 407 Life Science Bldg., 48202 Detroit, MI, USA.
RP Tang, GD (reprint author), Wayne State University, Biomide Laboratories, Detroit, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 179
EP 190
PG 12
ER
PT J
AU Ongradi, J
Specter, S
Horvath, A
Friedman, H
AF Ongradi, Joseph
Specter, Steven
Horvath, Attila
Friedman, Herman
TI Combined In Vitro Effect of Marijuana and Retrovirus on the Activity of Mouse Natural Killer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NK activity; retrovirus; marijuana; addition; mouse strains
ID NK activity; retrovirus; marijuana; addition; mouse strains
AB Both marijuana and retroviruses impair natural killer (NK) cell functions. No data on their simulataneous effects are available. Similarities to human AIDS induced early by Friend leukemia complex (FLC) and its replication competent helper Rowson-Parr virus (RPV) provides a mouse model to study drug-virus action. Leukemia suscep-tible BALB/c and resistant C57BL/6 mice were infected, then at time intervals their nylon wool-separated splenocytes were exposed to tetrahydrocannabinol (THC) for 3h.Natural killer (NK) cell activity against Yac-1 cells was assayed by 51Cr-release for 4 and 18h. Recovery of splenocytes was found to be suppressed by FLC, but in BALB/c only by RPV. After a transient enhancement in C57BL/6 by FLC, NK cell activity of both mice became suppressed early (2 to 4 days), normalized subsequently and enhanced late (11 to 14 days) postinfection. A moderate increase in BALB/c, no change in C57BL/6 were induced by low (1-2.5 µg/ml) THC doses. NK cell activity of BALB/c became suppressed exponentially by higher (5-10 µg/ ml) THC doses in 18h as compared to 4h assays, while its proportional and moderate impairment was seen in C57BL/6. The magnitude of NK cell activity of infected mice was determined by THC: enhancement or impairment followed those of untreated, infected counterparts, but on the level of THC-treated cells. Low doses hardly, high doses additively influenced NK cells of infected BALB/c. THC hardly affected very early and late enhancement in NK cell activiy of FLC infected C57BL/6, but augmented RPV induced suppression late in 18h assays. Genetic factors similar to endotoxin resistance, altered cytokine profile might determine these effects. Similar phenomena in humans might result in earlier manifestation of AIDS.
C1 [Ongradi, Joseph] The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-ImmunologyTampa, FL, USA.
[Specter, Steven] The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-ImmunologyTampa, FL, USA.
[Horvath, Attila] National Institute for Dermato-Venereology, Maria u. 41., H-1085 Budapest, Hungary.
[Friedman, Herman] The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-ImmunologyTampa, FL, USA.
RP Ongradi, J (reprint author), The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-Immunology, Tampa, USA.
EM ongjos@bor.sote.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 191
EP 199
PG 9
ER
PT J
AU Tornoczky, T
Kelenyi, G
Pajor, L
AF Tornoczky, Tamas
Kelenyi, Gabor
Pajor, Laszlo
TI EBER Oligonucleotide RNA in situ Hybridization in EBV Associated Neoplasms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EBV; EBER; microwave; LMP-1; lymphoma; Warthin's tumor; nasopharyngeal carcinoma
ID EBV; EBER; microwave; LMP-1; lymphoma; Warthin's tumor; nasopharyngeal carcinoma
AB In virus associated diseases identification of viruses in cells can contribute to the understanding of the pathogenesis and may also help to establish the diagnosis. In the present communication, the effects of the microwave pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr-Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods, latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also compared. Our results show that microwave pretreatment enhances the intensity of the ISH signals and preserves significantly better the structure of the tissues compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal carcinoma cases, showed a more frequent positivity than the immunohistochemical reaction for LMP-1, however in case of the Warthin?s tumor only the LMP-1 protein was expressed.
C1 [Tornoczky, Tamas] University of Pecs, Department of Pathology, Szigeti ut 12., H-7643 Pecs, Hungary.
[Kelenyi, Gabor] University of Pecs, Department of Pathology, Szigeti ut 12., H-7643 Pecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, Szigeti ut 12., H-7643 Pecs, Hungary.
RP Tornoczky, T (reprint author), University of Pecs, Department of Pathology, H-7643 Pecs, Hungary.
EM yst@pathology.pote.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 201
EP 205
PG 5
ER
PT J
AU Hrzenjak, MT
Popovic, M
Tiska-Rudman, L
AF Hrzenjak, M Terezija
Popovic, Maja
Tiska-Rudman, Ljerka
TI Fibrinolytic Activity of Earthworms Extract (G-90) on Lysis of Fibrin Clots Originated from the Venous Blood of Patients with Malignant Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE fibrinolytic activity; earthworms extract; fibrin clot; malignant tumors
ID fibrinolytic activity; earthworms extract; fibrin clot; malignant tumors
AB u-PA is secreted by the most malignant tumors. As a response to u-PA synthesis surrounding cells synthetize inhibitors of plasminogen activators for tissue protection. Plasminogen activators were found also in earthworm tissue. From the tissue homogenate of earthworm Eisenia foetida the glycolipoprotein mixture named G-90 was isolated. It contains two serine proteases (P I, P II) with fibrinolytic and anticoagulative activities. The fibrinolytic activity of G-90, P I and P II was tested in an in vitro euglobulinic test applied to fibrin clot from blood plasma of patients suffered from malignant tumors. G-90 and above-mentioned proteases applied in this study showed euglobulinic time proportionally with the concentrations of added substances. The influence of G-90 on the fibrinolysis rate does not depend only on its concentration, but depends too on histological type of tissue (organ) where the malignant tumors are located. Enzyme P I and P II do not show this activity.
C1 [Hrzenjak, M Terezija] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55, 10000 Zagreb, Croatia.
[Popovic, Maja] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55, 10000 Zagreb, Croatia.
[Tiska-Rudman, Ljerka] University Hospital for TumorsZagreb, Croatia.
RP Hrzenjak, MT (reprint author), Faculty of Veterinary Medicine, Department of Biology, 10000 Zagreb, Croatia.
EM mthrzenj@rudjer.irb.hr
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 206
EP 211
PG 6
ER
PT J
AU Leel-Ossy, L
Gati, I
AF Leel-Ossy, Lorant
Gati, Istvan
TI Corpus Amylaceum (Polyglucosan Body) in the Peripheral Olfactory System
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE corpus amylaceum; olfactory tract
ID corpus amylaceum; olfactory tract
AB Peripheral part of the olfactory system (bulb and tract) was investigated for the occurrence of corpus amylaceum (CA) (polyglucosan body) in 296 (281 pathological and 15 control cases) autopsied human brains. No significant differences were found in the incidence between the various age groups above 40 years or between different disease groups and the controls. The predominance of CA in the olfactory tract and its loose correlation with age at this localization over 40 years of age could be resulted by various factors, including the extremely rich astrocytic and capillary network in the intermediate zone, and the proximity of the olfactory tract to the external environment, which may result in the protective role of CA. The role of stress was proved by the HSP-60 positivity of CA.
C1 [Leel-Ossy, Lorant] St. Borbala University Hospital, Department of Pathology, Neuropathological Laboratory, H-2800 Tatabanya, Hungary.
[Gati, Istvan] University of Pecs, Department of NeurologyPecs, Hungary.
RP Leel-Ossy, L (reprint author), St. Borbala University Hospital, Department of Pathology, Neuropathological Laboratory, H-2800 Tatabanya, Hungary.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 212
EP 216
PG 5
ER
PT J
AU Szegedi, Zs
Amin, F
Szende, B
Bowen, DI
AF Szegedi, Zsolt
Amin, Farhana
Szende, Bela
Bowen, Delme Ivor
TI A New Method to Localize Acid Phosphatase Using the Confocal Laser-Scanning Microscope
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE acid phosphatase activity; cytometry; cell image analysis; confocal laser-scanning microscope
ID acid phosphatase activity; cytometry; cell image analysis; confocal laser-scanning microscope
AB The aim of the study was to work out a technique for the detection of acid phosphatase enzyme activity by confocal laser-scanning microscope using the histochemical acid phosphatase detection method (after Barka and Anderson 1962, modified by Bowen and Lewis 1985) routinely used for light microscopy. The density and the distribution of enzyme reaction product is dependent on the incubation time, as shown by different confocal images or ELISA reader. The inhibition of the enzyme activity with metal ions shows the same profile known from the literature. This staining method seems to be useful to demonstrate subcellular distribution of the enzyme in the lysosomes and in the Golgi apparatus.
C1 [Szegedi, Zsolt] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi ut 26., 1085 Budapest, Hungary.
[Amin, Farhana] University of Cardiff, Department of Pure and Applied BiologyCardiff, Wales, UK.
[Szende, Bela] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi ut 26., 1085 Budapest, Hungary.
[Bowen, Delme Ivor] University of Cardiff, Department of Pure and Applied BiologyCardiff, Wales, UK.
RP Szegedi, Zs (reprint author), Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, 1085 Budapest, Hungary.
EM szezso@korb1.sote.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 217
EP 223
PG 7
ER
PT J
AU Maldonado, JC
Palazzolo, K
Taylor, DJ
AF Maldonado, J Carlos
Palazzolo, Katherine
Taylor, D John
TI A Novel In Vitro System to Study Extravasated Tumor Cell-Induced Angiogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE blood vessels; collagen gel; extravasation; invasion; in vitro; metastasis; secondary angiogenesis
ID blood vessels; collagen gel; extravasation; invasion; in vitro; metastasis; secondary angiogenesis
AB Angiogenesis, the formation of new blood vessels from preexisting ones, is a fundamental stage in the metastatic pathway. For the primary tumor, this neovascularization provides nutrients and oxygen as well as a route by which metastatic tumor cells gain access to the circulatory system. Among these metastatic tumor cells, there are subgroups of cells that express an angiogenesis-inducing cells phenotype (AICs) as well as others that do not. Tumor cells not expressing the angiogenesis-inducing cells phenotype (non-AICs) invade new tissues and remain as dormant micrometastases unless they accompany AICs. Thus, either alone or with non-AICs, angiogenesis-inducing cells form rapidly growing, clinically detectable metastases. Much of the current research in this area is concentrated on the vascularization of primary tumors, but the regulation of angiogenesis by extravasating or invading tumor cells has not being extensively studied. We have developed a working model, which demonstrates that human metastatic prostate cancer cells (PC-3) appear to induce human vascular endothelial cells (HUVECs) to translocate across a Matrigel-coated 8 ?m membrane. The parameters of this model (i.e. pore size, seeding-cell density, seeding times) were established using highly invasive murine melanoma cells (B16F10) seeded on murine microvascular endothelial cells (CD3). We have further modified our model in order to include a host compartment made of collagen gel, in order to mimic the in vivo site of metastases-induced angiogenesis.
C1 [Maldonado, J Carlos] Wayne State University, Biological Sciences Department, 5047 Gullen Mall, 48202 Detroit, MI, USA.
[Palazzolo, Katherine] Wayne State University, Biological Sciences Department, 5047 Gullen Mall, 48202 Detroit, MI, USA.
[Taylor, D John] Wayne State University, Biological Sciences Department, 5047 Gullen Mall, 48202 Detroit, MI, USA.
RP Taylor, DJ (reprint author), Wayne State University, Biological Sciences Department, 48202 Detroit, USA.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 225
EP 229
PG 5
ER
PT J
AU Albini, A
AF Albini, Adriana
TI Tumor and Endothelial Cell Invasion of Basement Membranes The Matrigel Chemoinvasion Assay As A Tool For Dissecting Molecular Mechanisms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE invasion; metastasis; angiogenesis; basement membranes; matrigel; Boyden chamber; chemoinvasion
ID invasion; metastasis; angiogenesis; basement membranes; matrigel; Boyden chamber; chemoinvasion
AB The spread of cancer cells from a primary tumor to distant organs is the major cause of death of cancer patients. Metastatic lesions are often resistent to cancer therapy because of the progressive phenotypic changes that they have undergone. Several genetic and epigenetic factors, both in the cell and in the host, contribute to the development of tumor progression towards metastases. In this review we will analyze the steps involved in tumor metastases, which can be potential targets for anti-metastatic therapy. One of the most critical events in cancer metastasis is the invasion of basement membranes. An assay which we developed over ten years ago, the matrigel ''chemoinvasion'' assay, has been a useful tool for studying the mechanisms involved in tumor and endothelial cell invasion of basement membranes and for the screening of anti-invasive agents. Here we will describe the assay and review some of the major results obtained with it.
C1 [Albini, Adriana] National Institute for Research on Cancer, Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova, Italy.
RP Albini, A (reprint author), National Institute for Research on Cancer, Advanced Biotechnology Center, 16132 Genova, Italy.
EM albini@sirio.cba.unige.it
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1998
VL 4
IS 3
BP 230
EP 241
PG 12
ER
PT J
AU Szakacs, G
Jakab, K
Antal, F
Sarkadi, B
AF Szakacs, Gergely
Jakab, Katalin
Antal, Ferenc
Sarkadi, Balazs
TI Diagnostics of Multidrug Resistance in Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE P-glycoprotein; MDR1; MRP; multidrug transporters; diagnostic methods
ID P-glycoprotein; MDR1; MRP; multidrug transporters; diagnostic methods
AB Multidrug resistance (MDR), caused by the overexpression of two membrane proteins, MDR1-Pgp and/or MRP, is a major obstacle in the chemotherapy of cancer. The proper laboratory diagnosis of clinical multidrug resistance is still an unresolved question, and this uncertainty, in a vicious cycle, does not allow the correct evaluation of the clinical relevance of the MDR phenomenon. Moreover, inefficient MDR diagnostics hinders the development of effective resistance-modulation strategies. In this review, after describing the basic features of the MDR drug pump proteins, the currently employed diagnostic methods are discussed. We suggest that a quantitative, functional method developed in our laboratory may provide a major help in the laboratory assessment of cancer MDR.
C1 [Szakacs, Gergely] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi u. 24., H-1113 Budapest, Hungary.
[Jakab, Katalin] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi u. 24., H-1113 Budapest, Hungary.
[Antal, Ferenc] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi u. 24., H-1113 Budapest, Hungary.
[Sarkadi, Balazs] National Institute of Haematology, Blood Transfusion and Immunology, Daroczi u. 24., H-1113 Budapest, Hungary.
RP Sarkadi, B (reprint author), National Institute of Haematology, Blood Transfusion and Immunology, H-1113 Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 251
EP 257
PG 7
ER
PT J
AU Croce, VM
Colussi, GA
De Bravo, G
Price, RM
Segal-Eiras, A
AF Croce, V Maria
Colussi, G Andrea
De Bravo, M. Garcia
Price, R Michel
Segal-Eiras, Amanda
TI Immunohistopathological Characterization of Spontaneous Metastases in a Human Lung Mucoepidermoid Adenocarcinoma (HLMC) Xenograft
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistopathology; metastases; lung adenocarcinoma xenograft
ID immunohistopathology; metastases; lung adenocarcinoma xenograft
AB The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.
C1 [Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Colussi, G Andrea] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[De Bravo, M. Garcia] National University of La Plata, IMBIOLPLa Plata, Argentina.
[Price, R Michel] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research LaboratoriesNottingham, UK.
[Segal-Eiras, Amanda] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM aeiras@satlink.com
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 259
EP 266
PG 8
ER
PT J
AU Sipos, L
Szegedi, Zs
Fedorcsak, I
Afra, D
Szende, B
AF Sipos, Laszlo
Szegedi, Zsolt
Fedorcsak, Imre
Afra, Denes
Szende, Bela
TI Apoptosis and p53 Expression in Human Gliomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; p53 expression; gliomas; grade
ID apoptosis; p53 expression; gliomas; grade
AB Twenty-five human gliomas of different histological grade and type were studied for p53 expression by immunohistochemistry and for apoptosis using ApopTagTM method. p53 expression (percentage of positive cells) was highest in anaplastic astrocytomas, followed by low grade astrocytomas and surprisingly in glioblastomas. Granular cytoplasmic p53 positivity appeared in 4/5 low grade oligodendroglioma and in 2/5 low grade mixed oligoastrocytomas. The means of apoptosis index in the different tumor types ranged between 0.8 and 11.5 with the highest values in anaplastic astrocytoma and glioblastomas. Although the number of cases per group were relatively low and the individual vales showed differences it seems that p53 expression is related to the biological aggressiveness of gliomas. It is also suggested that high level of apoptosis in malignant glioma could represent a p53 independent pathway.
C1 [Sipos, Laszlo] National Institute of NeurosurgeryBudapest, Hungary.
[Szegedi, Zsolt] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Fedorcsak, Imre] National Institute of NeurosurgeryBudapest, Hungary.
[Afra, Denes] National Institute of NeurosurgeryBudapest, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 267
EP 270
PG 4
ER
PT J
AU Epelbaum, R
Shalitin, Ch
Segal, R
Valansi, C
Arselan, I
Faraggi, D
Leviov, M
Ben-Shahar, M
Haim, N
AF Epelbaum, Ron
Shalitin, Channa
Segal, Ruth
Valansi, Clari
Arselan, Ida
Faraggi, David
Leviov, Michelle
Ben-Shahar, Menahem
Haim, Nissim
TI Haptoglobin-related Protein as a Serum Marker in Malignant Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Haptoglobin-related protein; 21-kDa protein; ELISA; lymphoma
ID Haptoglobin-related protein; 21-kDa protein; ELISA; lymphoma
AB A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin's lymphoma (n=58) and Hodgkin's disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430x103 u/ml, range 0-4000x103) were significantly higher than in the control group (median 68x103 u/ml, range 0-180x103) (p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), ''B'' symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.
C1 [Epelbaum, Ron] Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
[Shalitin, Channa] Technion-Israel Intitute of Technology, Department of BiologyHaifa, Israel.
[Segal, Ruth] Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
[Valansi, Clari] Technion-Israel Intitute of Technology, Department of BiologyHaifa, Israel.
[Arselan, Ida] University of Haifa, Department of StatisticsHaifa, Israel.
[Faraggi, David] University of Haifa, Department of StatisticsHaifa, Israel.
[Leviov, Michelle] Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
[Ben-Shahar, Menahem] Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
[Haim, Nissim] Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
RP Epelbaum, R (reprint author), Rambam Medical Center, Department of Oncology, 31096 Haifa, Israel.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 271
EP 276
PG 6
ER
PT J
AU Szendroi, M
Arato, G
Ezzati, A
Huttl, K
Szavcsur, P
AF Szendroi, Miklos
Arato, Gabriella
Ezzati, Ali
Huttl, Kalman
Szavcsur, Peter
TI Aneurysmal Bone Cyst: its Pathogenesis Based on Angiographic, Immunohistochemical and Electron Microscopic Studies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE aneurysmal bone cyst; pathogenesis; angiography; histology
ID aneurysmal bone cyst; pathogenesis; angiography; histology
AB Based on angiographic, immunohistochemical as well as electron microscopic findings, authors outline a hypothesis for the etiopathogenesis of aneurysmal bone cysts. No changes were found at the arterial site in 16 studied aneurysmal bone cysts, with no signs of an arteriovenous shunt. In certain cases, however, dilated and tortous efferent veins became visible in the late venous phase. Due to the impedance of venous flow, the intracystic pressure increases and the small veins become dilated causing formation of aneurysmal slits. This is supported by the immunohistochemical finding that S-actin shows concentric arrangement around the aneurysmal cavities. Endothelial lining and basal membrane remnants were detectable in places, though the aneurysmal slits were devoid of continuous endothelial lining and basal membrane. We suggested that the aneurysmal bone cyst corresponds to a hemodynamic disturbance and is due to primary or secondary venous malformation of the bones.
C1 [Szendroi, Miklos] Semmelweis University, Department of Orthopedics, Karolina ut 27, H-1113 Budapest, Hungary.
[Arato, Gabriella] Haynal Imre University of Health Sciences, Institute of PathologyBudapest, Hungary.
[Ezzati, Ali] Semmelweis University, Department of Orthopedics, Karolina ut 27, H-1113 Budapest, Hungary.
[Huttl, Kalman] Semmelweis University, Department of Cardiovascular SurgeryBudapest, Hungary.
[Szavcsur, Peter] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
RP Szendroi, M (reprint author), Semmelweis University, Department of Orthopedics, H-1113 Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 277
EP 281
PG 5
ER
PT J
AU Nishimura, Y
Sameni, M
Sloane, FB
AF Nishimura, Yukio
Sameni, Mansoureh
Sloane, F Bonnie
TI Malignant Transformation Alters Intracellular Trafficking of Lysosomal Cathepsin D in Human Breast Epithelial Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cathepsin D; aspartic proteinase; lamp; microtubule; trafficking; breast cancer; Ras
ID cathepsin D; aspartic proteinase; lamp; microtubule; trafficking; breast cancer; Ras
AB Increased expression and alteration of intracellular trafficking of lysosomal cathepsins have been reported in malignant tumors, or in cells transformed by the transfection with the ras oncogene. In the present study, immortal MCF-10A human breast epithelial cells were transformed with the mutated ras oncogene. Both cell lines were investigated for changes in the intracellular localization of lysosomal cathepsin D and lamp-1 (lysosome-associated membrane protein) employing specific antibodies and confocal immunofluorescence microscopy. The results revealed that staining for cathepsin D along with for lamp-1 was mostly localized in the perinuclear region of MCF-10A cells. In contrast, the staining for these proteins was found to be widely distributed throughout the cytoplasm and at the cell periphery in MCF-10AneoT cells. The organization of microtubules, but not actin, appeared to differ between MCF-10A cells and their oncogenic ras transfectants. When the microtubules were depolymerized by treatment of MCF-10A cells with nocodazole, vesicles containing the lysosomal cathepsin D were dispersed in the cytoplasm and translocation of these vesicles to the cell periphery was observed. The intracellular localization of cathepsin D in the nocodazole-treated MCF-10A cells seemed to be similar to that observed in the oncogenic ras transfectants of these cells. When taxol, which inhibits microtubule depolymerization, was added to the culture medium of neoT cells, a polymerized microtubule network was observed, and the reclustering of cathepsin D and lamp-1 occurred in a unidirectional manner towards the perinuclear region. These findings support a model in which cytoskeletal microtubule organization is closely related to the trafficking of lysosomes/endodomes, and in which oncogenic ras interferes with such organization in human breast epithelial cells.
C1 [Nishimura, Yukio] Kyushu University, Faculty of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-0054 Fukuoka, Japan.
[Sameni, Mansoureh] Wayne State University, Department of PharmacologyDetroit, USA.
[Sloane, F Bonnie] Wayne State University, Department of PharmacologyDetroit, USA.
RP Nishimura, Y (reprint author), Kyushu University, Faculty of Pharmaceutical Sciences, 812-0054 Fukuoka, Japan.
EM nishimur@bioc.phar.kyushu-u.ac.jp
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 283
EP 296
PG 14
ER
PT J
AU Bajtai, A
Hidvegi, J
AF Bajtai, Attila
Hidvegi, Judit
TI The Role of Gastric Mucosal Dysplasia in the Development of Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric dysplasia; gastric cancer
ID gastric dysplasia; gastric cancer
AB It is widely acknowledged that most stomach carcinomas developed from dysplastic lesions of gastric mucosa. They can be found in known precancerous conditions as chronic gastritis, gastric adenoma, giant rugal hypertrophy, chronic peptic ulcer, gastric stump after partial resection and pernicious anemia. Several grading systems of gastric dysplasia have been suggested. Nagayo's or the ISGGC classification was applied to 367 biopsy specimens of 258 patients between 1979-1995. The frequency of moderate and severe dysplasia was 0,84% regarding all gastric endoscopies in the same period of time. Follow-up studies were performed in 56 cases in a period of 1-7 ys. In this group cancer developed during 14 patients. The authors' recommendation is to follow up the patients gastric dysplasia for least 10 ys after with diagnosis.
C1 [Bajtai, Attila] Fovarosi Uzsoki utcai Korhaz, Pathologia, Uzsoki u. 29., H-1145 Budapest, Hungary.
[Hidvegi, Judit] Fovarosi Uzsoki utcai Korhaz, Pathologia, Uzsoki u. 29., H-1145 Budapest, Hungary.
RP Bajtai, A (reprint author), Fovarosi Uzsoki utcai Korhaz, Pathologia, H-1145 Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 297
EP 300
PG 4
ER
PT J
AU Cserni, G
AF Cserni, Gabor
TI The Impact of Axillary Lymphadenopathy on Further Treatment in Breast Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; axillary metastasis; clinical staging; sampling; sentinel lymph node biopsy
ID breast cancer; axillary metastasis; clinical staging; sampling; sentinel lymph node biopsy
AB Clinical assessment is an important part of the breast cancer patients' work-up, but it has low sensitivity and specificity. In a retrospective study, histological slides of axillary clearance specimens were used to model palpability of the axillary lymph nodes. Obvious nodes (enlarged and involving considerable amount of lymphatic and/or metastatic tissue) and nodes equal to or larger than 1 cm or 1.5 cm were counted and the slides were subsequently reviewed. The false positive and negative rates expected on the basis of the model ranged from 24 to 72% and from 10 to 38%, respectively. This model (also valid for intraoperative assessment of nodal status by palpation) documents the lack of specificity of clinical staging of the axilla. These results question the practice of excluding patients with palpable axillary lymph node enlargement from less radical staging procedures such as axillary sampling or sentinel node biopsy
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 301
EP 303
PG 3
ER
PT J
AU Soda, G
Baiocchini, A
Bosco, D
Nardoni, S
Melis, M
AF Soda, Giuseppe
Baiocchini, Andrea
Bosco, Daniela
Nardoni, Stefano
Melis, Marco
TI Oral Focal Mucinosis of the Tongue
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE focal mucinosis; oral
ID focal mucinosis; oral
AB Oral focal mucinosis (OFM) is an uncommon clinicopathological entity which is considered to be the oral counterpart of cutaneous focal mucinosis and cutaneous myxoid cyst. It is comprised of a clinically elevated mass with a histological feature of localised areas of myxomatous connective tissue. The present study adds a rare case of OFM of the tongue to the literature, and we present a review of the most characteristic oral myxomatous lesions.
C1 [Soda, Giuseppe] University of Rome, Campus Bio-Medico, Department of Pathology, V. Le Regina Elena 324, 00161 Rome, Italy.
[Baiocchini, Andrea] University of Rome, Campus Bio-Medico, Department of Pathology, V. Le Regina Elena 324, 00161 Rome, Italy.
[Bosco, Daniela] University of Rome, Campus Bio-Medico, Department of Pathology, V. Le Regina Elena 324, 00161 Rome, Italy.
[Nardoni, Stefano] University of Rome, Campus Bio-Medico, Department of Pathology, V. Le Regina Elena 324, 00161 Rome, Italy.
[Melis, Marco] University of Rome, Campus Bio-Medico, Department of Pathology, V. Le Regina Elena 324, 00161 Rome, Italy.
RP Melis, M (reprint author), University of Rome, Campus Bio-Medico, Department of Pathology, 00161 Rome, Italy.
EM mmelis@axrma.uniromal.it
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 304
EP 307
PG 4
ER
PT J
AU Luttwak, Z
Koren, R
Veltman, V
Halpern, M
Manes, A
Lask, D
Siegal, A
AF Luttwak, Zvi
Koren, Rumelia
Veltman, Vladimir
Halpern, Marisa
Manes, Aaron
Lask, Dov
Siegal, Annette
TI Leiomyoma of the Urinary Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE bladder; leiomyoma
ID bladder; leiomyoma
AB Leiomyoma of the urinary bladder is a rarity but should be considered in the differential diagnosis of an intramural neoplasm. We report a case illustrating clinical and pathological features in particular the immunohistochemistry. Etiology and differential diagnosis are discussed.
C1 [Luttwak, Zvi] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Veltman, Vladimir] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Halpern, Marisa] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Manes, Aaron] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
[Lask, Dov] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
[Siegal, Annette] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
RP Koren, R (reprint author), A, Rabin Medical Center (Golda Campus), Department of Pathology, Petach Tikvah, Israel.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 308
EP 309
PG 2
ER
PT J
AU Naidoo, R
Chetty, R
AF Naidoo, Richard
Chetty, Runjan
TI The Application of Microsatellites in Molecular Pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE microsatellites; microsatellite analysis; microsatellite instability; allelic imbalance; genetic linkage; automated DNA sequencing
ID microsatellites; microsatellite analysis; microsatellite instability; allelic imbalance; genetic linkage; automated DNA sequencing
AB Present within the genome are large numbers of seemingly unimportant DNA segments arranged in repetitive units. Furthermore, these stretches of DNA contain variations or polymorphisms that are characteristic for an individual and results in a unique DNA fingerprint. Approximately 30% of the DNA repeat sequences are arranged as short tandem repeat sequences, which are called microsatellites. Microsatellites may consist of 1, 2 or 3 nucleotides; dinucleotides being the commonest. Microsatellites are characterised by being: stably inherited and hence highly conserved from one generation to the next, and unique to an individual and the same in different cells from the same individual. As a result of the above features, microsatellites can be used for personal identification, population genetic analysis and construction of evolutionary trees. In addition, they are located in several important gene loci and this allows microsatellites to be used as markers of disease and to provide information about individual gene status, especially in tumors. This can be accomplished by assessing allelic imbalance or loss of heterozygosity of a particular gene by analysing microsatellites located at specific loci in the gene. Recently, mutations within microsatellites have been described as a result of defective DNA repair mechanisms, resulting in the phenomenon of microsatellite instability. This has been implicated in the aetiopathogenesis of several hereditary and non-hereditary conditions. There are several ways of analysing microsatellites, the popular using radioactively-labelled primers and autoradiography. This method has several drawbacks, especially the use of radioactivity and interpretative/technical problems. The use of fluorescently-labelled primers, automated DNA sequencing coupled with a computer software package obviates these problems. This technique has the added advantage of analysing several microsatellites in large numbers of cases, simultaneously. Thus, microsatellite analysis has become an important investigative tool for the molecular biologist and has provided new information in many diseases.
C1 [Naidoo, Richard] University of Natal School of Medicine, Molecular Biology Research Facility and Department of Pathology, Private Bag 7, 4013 Congella, Durban, South Africa.
[Chetty, Runjan] University of Natal School of Medicine, Molecular Biology Research Facility and Department of Pathology, Private Bag 7, 4013 Congella, Durban, South Africa.
RP Naidoo, R (reprint author), University of Natal School of Medicine, Molecular Biology Research Facility and Department of Pathology, 4013 Congella, South Africa.
EM naidoor@med.und.ac.za
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 310
EP 315
PG 6
ER
PT J
AU Soti, Cs
Csermely, P
AF Soti, Csaba
Csermely, Peter
TI Molecular Chaperones in the Etiology and Therapy of Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE chaperone; heat shock protein; stress protein; metastasis; immunotherapy; drug resistance
ID chaperone; heat shock protein; stress protein; metastasis; immunotherapy; drug resistance
AB Molecular chaperones are ubiquitous, well-conserved proteins that account for 2-5 % of all cellular proteins in most cells. The present review summarizes our current knowledge about their involvement in the etiology and therapy of cancer with special emphasis on the expression of chaperones in malignant cells, their role in folding of (proto)oncogene products, cell cycle regulation, cell differentiation and apoptosis, development of metastasis, and their participation in the recognition of malignant cells. We also overview the importance of chaperones in hyperthermia, drug resistance, and recent approaches in chaperone-immunotherapy.
C1 [Soti, Csaba] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H-1444 Budapest, Hungary.
[Csermely, Peter] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H-1444 Budapest, Hungary.
RP Csermely, P (reprint author), Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H-1444 Budapest, Hungary.
EM csermely@puskin.sote.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 1998
VL 4
IS 4
BP 316
EP 321
PG 6
ER
PT J
AU Clay, MT
Custer, CM
Spiess, JP
Nishimura, IM
AF Clay, M Timothy
Custer, C Mary
Spiess, J Paul
Nishimura, I Michael
TI Potential Use of T Cell Receptor Genes to Modify Hematopoietic Stem Cells for the Gene Therapy of Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE adoptive immunotherapy; gene therapy; stem cell; T cell receptor; tumor antigen
ID adoptive immunotherapy; gene therapy; stem cell; T cell receptor; tumor antigen
AB The purpose of this review is to illustrate some of the technical and biological hurdles that need to be addressed when developing new gene therapy based clinical trials. Gene transfer approaches can be used to ''mark” cells to monitor their persistence in vivo in patients, to protect cells from toxic chemotherapeutic agents, correct a genetic defect within the target cell, or to confer a novel function on the target cell. Selection of the most suitable vector for gene transfer depends upon a number of factors such as the target cell itself and whether gene expression needs to be sustained or transient. The TCR gene transfer approach described here represents one innovative strategy being pursued as a potential therapy for metastatic melanoma. Tumor reactive T cells can be isolated from the tumor infiltrating lymphocytes (TIL) of melanoma patients. A retroviral vector has been constructed containing the T cell receptor (TCR) &agr; and &bgr; chain genes from a MART-1(27-35)-specific T cell clone (TIL 5). Jurkat cells transduced with this virus specifically release cytokine in response to MART-1(27-35) peptide pulsed T2 cells, showing that the virus can mediate expression of a functional TCR. HLA-A2 transgenic mice are being used to examine whether transduced bone marrow progenitor cells will differentiate in vivo into mature CD8+ T cells expressing the MART-1(27-35)-specific TCR. Expression of the human TCR &agr; and &bgr; chain genes has been detected by RT-PCR in the peripheral blood of HLA-A2 transgenic mice reconstituted with transduced mouse bone marrow. Expression of the TIL 5 TCR genes in the peripheral blood of these mice was maintained for greater than 40 weeks after bone marrow reconstitution. TIL 5 TCR gene expression was also maintained following transfer of bone marrow from mice previously reconstituted with transduced bone marrow to secondary mouse recipients, suggesting that a pluripotent progenitor or lymphocyte progenitor cell has been transduced.
C1 [Clay, M Timothy] National Institutes of Health, National Cancer Institute, Surgery Branch, Building 10, Room 2B04, 10 Center Drive, 20892 Bethesda, MD, USA.
[Custer, C Mary] National Institutes of Health, National Cancer Institute, Surgery Branch, Building 10, Room 2B04, 10 Center Drive, 20892 Bethesda, MD, USA.
[Spiess, J Paul] National Institutes of Health, National Cancer Institute, Surgery Branch, Building 10, Room 2B04, 10 Center Drive, 20892 Bethesda, MD, USA.
[Nishimura, I Michael] National Institutes of Health, National Cancer Institute, Surgery Branch, Building 10, Room 2B04, 10 Center Drive, 20892 Bethesda, MD, USA.
RP Clay, MT (reprint author), National Institutes of Health, National Cancer Institute, Surgery Branch, 20892 Bethesda, USA.
EM Tim_Clay@nih.gov.usa
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Rosenberg SA, Anderson WF, Blaese MR, et al: Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for interleukin-2. Human Gene Ther 3:75- 91, 1992.
Cassileth PA, Podack E, Sridhar K, et al: Phase I study of transfected cancer cells expressing the interleukin-2 gene product in limited stage small cell lung cancer. Human Gene Ther 6:369- 383, 1995.
Das Gupta TK, Cohen EP and Richards JM: Phase I evaluation of interleukin-2-transfected irradiated allogeneic melanoma for the treatment of metastatic melanoma, Human Gene Ther 8:1713-1726, 1997.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 9-10, 1994. Human Gene Ther 6:249-252, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 9-10, 1994. Human Gene Ther 6:255, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, September 12-13, 1994. Human Gene Ther 6:498-499, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, March 6-7, 1995. Human Gene Ther 6:1634-1636, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 8-9, 1995. Human Gene Ther 7:432-434, 1996.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 8-9, 1995. Human Gene Ther 7:432, 1996.
Rosenberg SA, Anderson WF, Asher AL, et al: Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for tumor necrosis factor. Human Gene Ther 3:57-73, 1992.
Berns AJM, Clift S, Cohen LK, et al: Phase I study of non-replicating autologous tumor cell injections using cells prepared with or without GM-CSF gene transduction in patients with metastaic renal cell carcinoma. Human Gene Ther 6:347-368, 1995.
Seigler HF, Darrow TL, Abdel-Wahab Z, et al: A phase I trial of human gamma interferon transduced autologous tumor cells in patients with disseminated malignant melanoma. Human Gene Ther 5:761-773, 1994.
Dranoff G, Soiffer R, Lynch T, et al: A phase I study of vaccination with autologous, irradiated melanoma cells engineered to secrete human granulocyte-macrophage colony stimulating factor. Human Gene Ther 8:111-123, 1997.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, March 6-7, 1995. Human Gene Ther 6:1631-1634, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, September 11-12. Human Gene Ther 7:1033, 1996.
Lotze MT, Rubin JT, Carty S, et al: Gene therapy of cancer: a pilot study of IL-4-gene-modified fibroblasts admixed with autologous tumor to elicit an immune response. Human Gene Ther 5:41-55, 1994.
Sobol RE, Royston I, Fakhrai H, et al: Injection of colon carcinoma patients with autologous irradiated tumor cells and fibroblasts genetically modified to secrete interleukin-2, IL-2): a phase I study. Human Gene Ther 6:195-204, 1995.
Tahara H, Lotze MT, Robbins PD, et al: IL-12 gene therapy using direct injection of tumors with genetically engineered autologous fibroblasts. Human Gene Ther 6:1607-1624, 1995.
Deisseroth AB, Kavanagh J, Champlin R: Use of safety-modified retroviruses to introduce chemotherapy resistance sequences into normal hematopoietic cells for chemoprotection during the therapy of ovarian cancer: a pilot trial. Human Gene Ther 5:1507-1522, 1994.
Hesdorffer C, Antman K, Bank A, et al: Human MDR gene transfer in patients with advanced cancer. Human Gene Ther 5:1151-1160, 1994.
OShaughnessy JA, Cowan KH, Nienhuis AW, et al: Retroviral mediated transfer of the human multidrug resistance gene, MDR-1, into hematopoietic stem cells during autologous transplantation after intensive chemotherapy for metastatic breast cancer. Human Gene Ther. 5:891-911, 1994.
Deisseroth AB, Holmes F, Hortobagyi G, et al: Use of safetymodified retroviruses to introduce chemotherapy resistance sequences into normal hematopoietic cells for chemoprotection during the therapy of breast cancer; a pilot trial. Human Gene Ther 7:401-416, 1996.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 7-8, 1993. Human Gene Ther 5:537- 539, 1994.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, September 11-12, 1995. Human Gene Ther 5:1036- 1038, 1996.
Holt JA, Arteaga CB, Robertson D, et al: Gene therapy for the treatment of metastatic breast cancer by in vivo transduction with breast-targeted retroviral vector expressing antisense c-fos RNA. Human Gene Ther 7:1369-1380, 1996.
Roth JA: Modification of tumor supressor gene expression in non-small cell lung cancer, NSCLC, with a retroviral vector expressing wildtype, normal, p53. Human Gene Ther 7:861- 874, 1996.
Roth JA: Modification of tumor supressor gene expression and induction of apoptosis in non-small cell lung cancer, NSCLC, with an adenovirus vector expressing wildtype p53 and cisplatin. Human Gene Ther 7:1013-1030, 1996.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 12-13, 1997. Human Gene Ther 9:394-402, 1998.
Culver KW, van Gilder J, Link CJ, et al: Gene therapy for the treatment of malignant brain tumors with in vivo tumor transduction with the Herpes Simplex thymidine kinase gene/ganciclovir system. Human Gene Ther 5:343-379, 1994.
Raffel C, Culver KW, Kohn D, et al: Gene therapy for the treatment of recurrent pediatric malignant astrocytomas with in vivo tumor transduction with the Herpes Simplex thymidine kinase gene/ganciclovir system. Human Gene Ther 5:863-890, 1994.
Galpin JE, Casciato DA, Richards SB: A phase I clinical trial to evaluate the safety and biological activity of HIV-IT(TAF)(HIV- 1IIIBenv-transduced, autologous fibroblasts, in asymptomatic HIV-1 infected subjects. Human Gene Ther 5:997-1017, 1994.
Nabel GJ, Fox BA, Post L, et al: A molecular genetic intervention for AIDS – effects of a transdominant negative form of Rev. Human Gene Ther 5:79-92, 1994.
Haubrich R, McCutchan JA: An open label, phase I/II clinical trial to evaluate the safety and biological activity of HIVIT( V)(HIV-1IIIB env/env retroviral vector, in HIV-1-infected subjects. Human Gene Ther 6:941-959, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, September 9-10, 1993. Human Gene Ther 5:655-657, 1994.
Morgan R and Walker, R: Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins. Human Gene Ther 7:1281-1306, 1996.
Crystal RG, Jaffe A, Brody S, et al: A phase I study, in cystic fibrosis patients, of the safety, toxicity, and biological efficacy of a single administration of a replication deficient, recombinant adenovirus carrying the cDNA of the normal cystic fibrosis transmembrane conductance regulator gene in the lung. Human Gene Ther 6:643-666, 1995.
Wilson JM, Engelhardt JF, Grossman M, et al: Gene therapy of cystic fibrosis lung disease using E1 deleted adenoviruses: a phase I trial. Human Gene Ther 5:501-519, 1994.
Welsh MJ, Smith AE, Zabner J, et al: Cystic fibrosis gene therapy using an adenovirus vector: in vivo safety and efficacy in nasal epithelium. Human Gene Ther 5:209-219, 1994.
Wilmott RW, Whitsett JA, Trapnell B, et al: Gene therapy for cystic fibrosis utilizing a replication deficient recombinant adenovirus vector to deliver the human cystic fibrosis transmembrane conductance regulator cDNA to the airways. A phase I study. Human Gene Ther 5:1019-1057, 1994.
Boucher RC, Knowles MR, Johnson LG, et al: Gene therapy for cystic fibrosis using E1-deleted adenovirus: a phase I trial in the nasal cavity, the University of North Carolina. Human Gene Ther 5:615-639, 1994.
Sorcher EJ, Logan JJ, Frizzell RA, et al: Gene therapy for cystic fibrosis using cationic liposome mediated gene transfer: a phase I trial of safety and efficacy in the nasal airway. Human Gene Ther 5:1261-1279, 1994.
Welsh MJ, Zabner J, Graham SM, et al: Adenovirus-mediated gene transfer for cystic fibrosis: Part A. Safety of dose and repeat administration in the nasal epithelium. Part B. Clinical efficacy in the maxillary sinus. Human Gene Ther. 6:205-218, 1995.
Flotte TR, Carter B, Conrad C, et al: A phase I study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease. Human Gene Ther 7:1145-1159, 1996.
Crystal RG, Mastrangeli A, Sanders A, et al: Evaluation of repeat administration of a replication deficient, recombinant adenovirus containing the normal cystic fibrosis transmembrane conductance regulator cDNA to the airways of individuals with cystic fibrosis. Human Gene Ther 6:667-703, 1995.
Dunbar C, Kohn D, Karlsson S, et al: Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with Gaucher disease. A phase I study. Human Gene Ther 7:231-253, 1996.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, December 2-3, 1993. Human Gene Ther 5:1178-1180, 1994.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, June 9-10, 1994. Human Gene Ther 6:246-247, 1995.
Department of Health and Human Services, National Institutes of Health Recombinant DNA Advisory Committee, minutes of meeting, September 12, 1997. Human Gene Ther 9, 914, 1998.
Whitley CB, McIvor RS, Aronovich EL, et al: Retroviral-mediated transfer of the Iduronate-2-sulfatase gene into lymphocytes for treatment of mild Hunter syndrome, Mucopolysaccharidosis Type II). Human Gene Ther 7:537-549, 1996.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 3
EP 15
PG 13
ER
PT J
AU Pillay, P
Chetty, R
Reddy, R
AF Pillay, Preedashnie
Chetty, Runjan
Reddy, Roshilla
TI Bcl-2 and p53 Immunoprofile in Kaposi's Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bcl-2; p53; Kaposi's sarcoma
ID bcl-2; p53; Kaposi's sarcoma
AB Seventy three cases of Kaposi's sarcoma (KS) from the 3 histological subtypes (patch, plaque and nodular) were assessed for bcl-2 and p53 protein expression. The aim was determine the level of expression of these proteins in KS and in the different subtypes. Commercially available antibodies to bcl-2 and p53 were applied after both microwave and pressure cooking antigen retrieval. Bcl-2 immunoexpression increased from the patch stage (36%) to the plaque stage (45%) to the nodular stage (70.83%). Better immunostaining for bcl-2 was obtained after pressure cooking. p53 on the other hand, was not expressed in the patch or plaque stages, but 54.16% of cases in the nodular stage were immunopositive. These results show a progression of immunoexpression of both bcl-2 and p53 from the early histological stages to the late tumor stage, implying that these proteins are upregulated late in the evolution of KS.
C1 [Pillay, Preedashnie] University of Natal Medical School, Private Bag 7, Congella, 4013 Durban, South Africa.
[Chetty, Runjan] University of Natal Medical School, Private Bag 7, Congella, 4013 Durban, South Africa.
[Reddy, Roshilla] University of Natal Medical School, Private Bag 7, Congella, 4013 Durban, South Africa.
RP Pillay, P (reprint author), University of Natal Medical School, 4013 Durban, South Africa.
EM pillayp11@med.und.ac.za
CR Bellamy COC: p53 and apoptosis. Brit Med Bull 53:522, 1996.
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Li JL, Huang Yau-Q, Cockerell CJ, et al: Expression and mutation of the tumor suppressor gene p53 in AIDS-associated Kaposi’s sarcoma. Am J Dermatopathol 19:373, 1997.
Dada MA, Chetty R, Biddolph SC, et al: The immunoexpression of bcl-2 and p53 in Kaposi’s sarcoma. Histopathology 29:159- 163, 1996.
Morris CB, Gendelman R, Marrogi AJ, et al: Immunohistochemical detection of bcl-2 in AIDS-associated and classical Kaposi’s sarcoma. Am J Pathol 148:1055-1063 1996.
Chor PJ, Cruz DJ: Kaposi’s sarcoma – A clinicopathologic review and differential diagnosis. J Cutan Pathol 19:6-20, 1992.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 17
EP 20
PG 4
ER
PT J
AU Rathore, A
Kamarajan, P
Mathur, M
Sinha, S
Sarkar, Ch
AF Rathore, Annapurna
Kamarajan, Pacchapam
Mathur, Meera
Sinha, Subrata
Sarkar, Chitra
TI Simultaneous Alterations of Retinoblastoma and p53 Protein Expression in Astrocytic Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE astrocytic tumors; p53; pRb; immunochemistry; survival
ID astrocytic tumors; p53; pRb; immunochemistry; survival
AB The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpressions is thought to indicate defective tumor supression and subsequently more aggressive tumors. Therefore, to assess the alterations in the conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded sections, 64 astrolytic tumors were studied (16 astrocytomas, 7 gemistocytic astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be positive for p53 protein. Seventeen of these showed aberrant heterogenous staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors, simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases. This was more commonly observed among glioblastoma cases (7/22). No statistical difference was found between the survival rate of heterogenous pRb and p53 positivity in different grades of tumors. In glioblastomas, the survival rate appeared to be less in patients expressing heterogenous pRb, but this was not statistically significant. These results lead us to suspect that p53 and pRb pathways are inactivated, either throught mutation or as part of the neoplastic process in astrocytic tumors.
C1 [Rathore, Annapurna] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Kamarajan, Pacchapam] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Mathur, Meera] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Sinha, Subrata] All India Institute of Medical Sciences, Department of BiochemistryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM Sarkarch@medinst.ernet.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 21
EP 27
PG 7
ER
PT J
AU Vosianov, FA
Romanenko, MA
Zabarko, BL
Szende, B
Wang, YCh
Landas, S
Haas, PG
AF Vosianov, F Alexander
Romanenko, M Alina
Zabarko, B Larisa
Szende, Bela
Wang, Y Ching
Landas, Steven
Haas, P Gabriel
TI Prostatic Intraepithelial Neoplasia and Apoptosis in Benign Prostatic Hyperplasia Before and After the Chernobyl Accident in Ukraine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostate; PIN; BPH; apoptosis; ionizing radiation
ID prostate; PIN; BPH; apoptosis; ionizing radiation
AB The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients operated in 1984 before the accident (Group I), and 47 patients from the low contamined Kiev City (Group II) and 76 from high contaminated area (Group III) operated between 1996 and 1998. Their BPH samples were examined histologically and immunohistochemically. The incidences of prostatic intraepithelial neoplasia (PIN) and high grade PIN (HGPIN) were 15.5 and 11.1% in Group I, 29.8 and 14.9% in Group II, and 35.5 and 19.7% in Group III. The difference between the incidences of PIN in Group I and III is signficant (p<0.02). There was increased apoptosis in areas of PIN in Group II and III as compared to Group I (p<0.001). Since apoptosis has been shown to be associated with ionizing radiation and it is now found to be associated with PIN in patients diagnosed after the Chernobyl nuclear accident, this suggests that lon-term low dose internal ionizing radiation potentially may cause prostate cancer.
C1 [Vosianov, F Alexander] Academy of Medical Sciences of Ukraine, Departments of Pathology and Urology, Institute of Urology and NephrologyKiev, Ukraine.
[Romanenko, M Alina] Academy of Medical Sciences of Ukraine, Departments of Pathology and Urology, Institute of Urology and NephrologyKiev, Ukraine.
[Zabarko, B Larisa] Academy of Medical Sciences of Ukraine, Departments of Pathology and Urology, Institute of Urology and NephrologyKiev, Ukraine.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H1085 Budapest, Hungary.
[Wang, Y Ching] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H1085 Budapest, Hungary.
[Landas, Steven] State University of New York Health Science Center, Departments of Urology and PathologySyracuse, USA.
[Haas, P Gabriel] State University of New York Health Science Center, Departments of Urology and PathologySyracuse, USA.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 28
EP 31
PG 4
ER
PT J
AU Magyarosy, E
Martin, WJ
Chu, WE
Martin, ES
AF Magyarosy, Edina
Martin, W John
Chu, W Elizabeth
Martin, E Sue
TI Differential Diagnostic Significance of The Paucity of HLA-I Antigens on Metastatic Breast Carcinoma Cells in Effusions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HLA-A; B; C antigens; breast cancer; metastasis; cytology
ID HLA-A; B; C antigens; breast cancer; metastasis; cytology
AB Distinction between benign reactive mesothelial cells and metastatic breast adenocarcinoma cells in effusions from patients with a known prior history of breast cancer is not the easiest task in diagnostic pathology. Here, we report the usefulness of testing the expression of class I HLA antigens (HLA A, B, C) in this respect. Cytospins were prepared from effusions of patients without the history of breast cancer (5 cases) and from effusions of patients with infiltrating ductal carcinoma (11 cases). Three effusions from cancerous patients were not malignant cytologically. The expression of HLA-A, B, C, HLA-DR and ß2-microglobulin as well as the macrophage antigen, CD14, was evaluated by immunocytochemistry. In 10 of 11 effusions the cytologically malignant cells expressed very weak or undetectable HLA-A,B,C as compared to the mesothelial cells and macrophages. The paucity of expression of HLA-A, B, C was detectable in those 3 cases where a definitive cytological diagnosis of malignancy could not be established. In contrast, mesothelial cells and macrophages from all samples were uniformly and strongly positive for both HLA-A, B, C and ß2-microglobulin. We conclude that the paucity of HLA-I antigens provides a marker helpful in distinguishing metastatic breast carcinoma cells from reactive mesothelial cells in effusions.
C1 [Magyarosy, Edina] National Cancer Institute of Health, Department of PathologyBethesda, USA.
[Martin, W John] University of Health Sciences, Department of PathologyBethesda, USA.
[Chu, W Elizabeth] National Cancer Institute of Health, Department of PathologyBethesda, USA.
[Martin, E Sue] National Cancer Institute of Health, Department of PathologyBethesda, USA.
RP Magyarosy, E (reprint author), National Cancer Institute of Health, Department of Pathology, Bethesda, USA.
CR Corsdon JM, Pinkus GS: Mesothelioma: profile of keratin proteins and carcinoembryonic antigen. Am J Pathol 108:80-87, 1982.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 32
EP 35
PG 4
ER
PT J
AU Dogusoy, G
Karayel, AF
Gocener, S
Goksel, S
AF Dogusoy, Gulen
Karayel, Anik Ferah
Gocener, Selda
Goksel, Suha
TI Histopathologic Features and Expression of Bcl-2 and p53 Protein in Primary Gastric Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lymphoma; MALT; stomach; histopathology; bcl-2; p53
ID lymphoma; MALT; stomach; histopathology; bcl-2; p53
AB The aim of this study is to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas which were reclassified according to the concept of mucosa associated lymphoid tissue (MALT). The resected specimens from 41 patients with primary gastric lymphoma were investigated retrospectively. Immunohistochemical study was done to analyze the immunophenotype and bcl-2 and p53 proteins expression. Twenty three of the cases had tumors mainly located in the antrum. Histologically, 12 were low grade and 20 were high grade B-cell lymphoma of MALT, 9 other B-cell nonHodgkin’s lymphomas. Helicobacter pylori was identified in 72% of the cases. According to Musshoff’s modification, most of the MALT lymphoma cases had stage I or II disease. There was significant difference between low and high grade cases, in respect to depth of invasion in gastric wall. Immunohistochemically, the neoplastic cells in all MALT lymphomas, expressed B-cell phenotype. bcl-2 protein was found to be expressed in 59% and p53 protein expression was detected in 72% of cases. Among the B-cell lymphoma of MALT, bcl-2 positivity decreased and p53 positivity increased significantly as the histological grade advanced. So, an inverse correlation was observed between the expression of bcl-2 and p53. In conclusion, most primary gastric lymphomas are low or high grade B-cell MALT lymphomas and appear to arise in MALT acquired as a reaction to Helicobacter pylori infection. Expression of bcl-2 and p53 in gastric lymphomas may be associated with transformation from low-grade to high-grade disease.
C1 [Dogusoy, Gulen] Istanbul Medical Faculty, Department of Pathology, Cerrahpasa Tip Fakultesi, Patoloji ABD, 34303 Istanbul, Aksar, Turkey.
[Karayel, Anik Ferah] Istanbul Medical Faculty, Department of Pathology, Cerrahpasa Tip Fakultesi, Patoloji ABD, 34303 Istanbul, Aksar, Turkey.
[Gocener, Selda] Istanbul Medical Faculty, Department of Pathology, Cerrahpasa Tip Fakultesi, Patoloji ABD, 34303 Istanbul, Aksar, Turkey.
[Goksel, Suha] Istanbul Medical Faculty, Department of Pathology, Cerrahpasa Tip Fakultesi, Patoloji ABD, 34303 Istanbul, Aksar, Turkey.
RP Dogusoy, G (reprint author), Istanbul Medical Faculty, Department of Pathology, 34303 Istanbul, Turkey.
CR Chan JKC, Isaacson P: Relationship between high-grade lymphoma and low-grade B-cell mucosa-associated lymphoid tissue lymphoma, MALToma, of the stomach. Am J Pathol 136:1153-1164, 1990.
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Genta RM, Hamner W, Graham DY: Gastric lymphoid follicles in Helicobacter pylori infection. Hum Pathol 24:577-583, 1993.
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Hsi ED, Eisbruch A, Greenson JK, et al: Classification of primary gastric lymphomas according to histologic features. Am J Surg Pathol 22:17-27, 1998.
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Laszewski MJ, Kamat D, Kemp JD, et al: Immunophenotypic and genotypic characterization of primary non-Hodgkins lymphoma of the gastrointestinal tract. Modern Pathology 3:423- 429, 1990.
Lavergne A, Kanavaros P, Galian A: Primary B-cell gastric lymphomas of mucosa-associated lymphoid tissue. Histological and immunohistochemical study of ten cases on surgical specimens. Histol Histopath 7:129-136, 1992.
Mielke B, Moller P: Histomorphologic and immunophenotypic spectrum of primary gastrointestinal B-cell lymphomas. Int J Cancer 47:334-343, 1991.
Nakamura S, Akazawa K, Yao T et al: Primary gastric lymphoma. A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 76:1313- 1324, 1995.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 36
EP 40
PG 5
ER
PT J
AU Guran, S
Tali, ET
AF Guran, Sefik
Tali, E Turgut
TI p53 and p16INKA4A Mutations During the Progression of Glomus Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glomus tumor; p53; p16INKA4A; LOH
ID glomus tumor; p53; p16INKA4A; LOH
AB Glomus tumors are significantly rare tumors of carotid body. The great majority of these tumors are benign in character. Here we present two brothers with hereditary glomus jugulare tumor who had consanguineous parents. Radiotherapy was applied approximately 8 and 10 years ago for treatment in both cases. Eight years later, one of these cases came to our notice due to relapse. The mutation pattern of p53, p57KIP2, p16INK4A and p15NK4B genes which have roles in the cell cycle, was analyzed in tumor samples obtained from the two affected cases in the initial phase and from one of these cases at relapse. The DNA sample obtained from the case in initial diagnosis phase revealed no p53, p57KIP2, p16INK4A or p15INK4B mutation. He is still in remission phase. Despite the lack of p53, p57KIP2, p16INK4A and p15INK4B mutation at initial diagnosis the tumor DNA of the other case in relapse revealed p53 codon 243 (ATG->ATC; met->ile) and p16 codon 97 (GAC->AAC; asp->asn) missense point mutations. No loss of heterozygosity in p53 and p16INK4A was observed by microsatellite analysis of tumoral tissues in these cases. P53 and p16IINK4A mutations observed in relapse phase were in conserved regions of both genes. No previous reports have been published with these mutations in glomus tumor during progression. The mutation observed in this case may due to radiotherapy. In spite of this possibility, the missense point mutations in conserved region of p53 and p16INK4A genes may indicate the role of p53 and p16INK4A in tumor progression of glomus tumors.
C1 [Guran, Sefik] Gulhane Medical Faculty, Department of Medical Biology and Genetics, 06018 Ankara, Etlik, Turkey.
[Tali, E Turgut] Gazi Medical Faculty, Department of RadiologyAnkara, Turkey.
RP Guran, S (reprint author), Gulhane Medical Faculty, Department of Medical Biology and Genetics, 06018 Ankara, Turkey.
EM gurans@gata.edu.tr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 41
EP 45
PG 5
ER
PT J
AU Karthikeyan, K
Masilamani, V
Govindasamy, S
AF Karthikeyan, K. Krishnamoorthy
Masilamani, Vadivel
Govindasamy, Swaminathan
TI Spectofluorimetric Detection of DMBA-Induced Mouse Skin Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mouse skin carcinoma; plasma; erythrocytes; erythrocyte membrane; fluorescent intensity; fluorophors
ID mouse skin carcinoma; plasma; erythrocytes; erythrocyte membrane; fluorescent intensity; fluorophors
AB An attempt has been made to evaluate the normal and cancer blood samples of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mouse skin carcinoma by spectrofluorimetric method. Analysis of acetone extracts of plasma, erythrocyte and erythrocyte membrane showed an alteration around 630 nm when excited at 400 nm by cancer samples, compared to normal samples. The ratio of fluorescent intensity at 530 nm/630 nm was found to be decreased in erythrocyte and plasma and increased in erythrocyte membrane. These changes are not detectable in both hemolysates. It has been suggested that erythrocyte may be the carriers of fluorophors that accumulate in the cancer tissue and may be useful in the diagnosis and treatment of malignancies.
C1 [Karthikeyan, K. Krishnamoorthy] University of Madras, Department of Biochemistry and Molecular Biology, 600 025 Madras, India.
[Masilamani, Vadivel] Anna University, Department of Physics, Centre for Laser TechnologyMadras, India.
[Govindasamy, Swaminathan] University of Madras, Department of Biochemistry and Molecular Biology, 600 025 Madras, India.
RP Govindasamy, S (reprint author), University of Madras, Department of Biochemistry and Molecular Biology, 600 025 Madras, India.
EM sgsamy@unimad.ernet.in
CR Balasubramanian S, Elangovan V, Govindasamy S: Fluorescence spectroscopic identification of 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Carcinogenesis 16:2461-2465, 1995.
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Karthikeyan K, Ravichandran P, Govindasamy S: Chemopreventive effect of Ocimum sanctum on DMBA-induced hamster buccal pouch carcinogenesis. Oral Oncol 35:112-119, 1999.
Vengadesan N, Aruna P, Ganesan S: Characterization of native fluorescence from DMBA-treated hamster cheek pouch buccal mucosa for measuring tissue transformation. Br J Cancer 77:391-395, 1998.
Wenghong L: Some fluorescence observation on the canceration tissue and blood of cancer patients. SPIE 1054:196-199, 1989.
Xu X, Meng JW, Hou S: The characteristic fluorescence of the serum of cancer patients. J Lumin 40-41, 219-220, 1988.
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Zonios G: Spectral pathology. Ann NY Acad Sci 838:108-115, 1998.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 46
EP 48
PG 3
ER
PT J
AU Onoda, MJ
Kantak, SS
Diglio, AC
AF Onoda, M James
Kantak, S Seema
Diglio, A Clement
TI Radiation Induced Endothelial Cell Retraction in vitro: Correlation with Acute Pulmonary Edema
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiation; lung; edema
ID radiation; lung; edema
AB We determined the effects of low dose radiation (<200 cGy) on the cell-cell integrity of confluent monolayers of pulmonary microvascular endothelial cells (PMEC). We observed dose- and time-dependent reversible radiation induced injuries to PMEC monolayers characterized by retraction (loss of cell-cell contact) mediated by cytoskeletal F-actin reorganization. Radiation induced reorganization of F-actin microfilament stress fibers was observed >30 minutes post irradiation and correlated positively with loss of cell-cell integrity. Cells of irradiated monolayers recovered to form contact inhibited monolayers >24 hours post irradiation; concomitantly, the depolymerized microfilaments organized to their pre-irradiated state as microfilament stress fibers arrayed parallel to the boundaries of adjacent contact-inhibited cells. Previous studies by other investigators have measured slight but significant increases in mouse lung wet weight >1 day post thoracic or whole body radiation (>500 cGy). Little or no data is available concerning time intervals <1 day post irradiation, possibly because of the presumption that edema is mediated, at least in part, by endothelial cell death or irreversible loss of barrier permeability functions which may only arise >1 day post irradiation. However, our in vitro data suggest that loss of endothelial barrier function may occur rapidly and at low dose levels (<200 cGy). Therefore, we determined radiation effects on lung wet weight and observed significant increases in wet weight (standardized per dry weight or per mouse weight) in <5 hours post thoracic exposure to 50-200 cGy x-radiation. We suggest that a single fraction of radiation even at low dose levels used in radiotherapy, may induce pulmonary edema by a reversible loss of endothelial cell-cell integrity and permeability barrier function.
C1 [Onoda, M James] Wayne State University, Department of Radiation OncologyDetroit, USA.
[Kantak, S Seema] Wayne State University, Department of Radiation OncologyDetroit, USA.
[Diglio, A Clement] Wayne State University, Department of Radiation OncologyDetroit, USA.
RP Onoda, MJ (reprint author), Wayne State University, Department of Radiation Oncology, Detroit, USA.
CR Jochelson MS, Tarbell MJ, Weinstei, HJ: Unusual thoracic radiographic findings in children treated for Hodgkin’s disease. J Clin Oncol 4:6-12, 1986.
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Eldor A, Vlodavsky I, Hyam E, et al: Effect of radiation on prostacyclin production by cultured endothelial cells. Prostaglandins 25:263-279, 1983.
Farrukh IS, Michael JR, Peters SP, et al: The role of cyclooxygenase and lipoxygenase mediators in oxidant-induced lung injury. Am Rev Respir Dis 137:1343-1349, 1988.
Ward PA, Sulavik MC, Johnson KJ: Rat neutrophil activation and effects of lipoxygenase and cyclooxygenase inhibitors. Am J Pathol 116:223-233, 1984.
Kantak SS, Diglio CA, Onoda JM: Low dose radiationinduced endothelial cell retraction. Int J Radiat Biol 64:319- 328, 1993.
Siemann DW, Hill RP, Penny DP: Early and late pulmonary toxicity in mice evaluated 180 and 420 days following lung radiation. Radiat Res 89:386-407, 1982.
Jennings FL, Arden A: Development of radiation pneumonitis. Arch Path 74:351-360, 1962.
Gross NJ: Pulmonary effects of radiation therapy. Ann Int Med 86:81-92, 1977.
Germon PA, Brady LW: Physiologic changes before and after radiation treatment for carcinoma of the lung. J Am Med Assoc 206:809-814, 1968.
Prato FS, Kurdyak R, Saibil EA, et al: Physiologic and radiologic assessment during the development of pulmonary radiation and fibrosis. Radiology 122:398-397, 1977
Mah K, VanDyke J, Keane T, et al: Acute radiation-induced pulmonary damage:A clinical study on the response of fractionated radiation therapy. Int J Rad Onc Biol Phy 13:179-188, 1987.
Fenessey FJ: Irradiation damage to the lung. J Thoracic Imag 2:68-79, 1987.
Evans ML, Graham MM, Mahler PA, et al: Use of steroids to suppress vascular response to radiation. Int J Rad Onc Biol Phy 13:563-567, 1987.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 49
EP 55
PG 7
ER
PT J
AU Graf, M
Blaeker, H
Herwart, FO
AF Graf, Matthias
Blaeker, Hendrik
Herwart, F Otto
TI Extraurinal Metastasizing Ependymoma of the Spinal Cord
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE extraneural metastases; intraspinal tumor; ependymoma
ID extraneural metastases; intraspinal tumor; ependymoma
AB This paper reports a case of the rare entity of an extraneural metastasizing ependymoma of the spinal cord. The tumor which arose in the conus medullaris and in the cauda equina was first diagnosed in 1956 when a thoracolumbar myeloresection was performed. At autopsy, 40 years after the primary diagnosis, a massive local tumor recurrence with extraneural metastases in the lungs, the pleura, the liver, and the thoracal and abdominal lymph nodes were found. Immunohistochemical stains of the extraneural metastases showed a strongly cytoplasmatic expression of glial fibrillary acidic protein (GFAP). Neither the primary tumor nor its metastases showed any of the conventional morphological criteria of malignancy. Reviewing the literature we discuss the possible mechanism of extraneural tumor spread and the incidence of metastases with regard to the tumor type.
C1 [Graf, Matthias] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Blaeker, Hendrik] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
RP Graf, M (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM matthias_graf@ukl.uni-heidelberg.de
CR Bailey P, Cushing H: A classification of the tumors of the glioma group on a histogenetic basis with a correlation study of prognosis. J. B. Lippincott, Philadelphia, 1926.
Berger MS, Baumeister B, Geyer JR, et al: The risks of metastases from shunting in children with primary central nervous system tumors. J Neurosurg 74:872-877, 1991.
Birchmeier W, Weidner KM, Hulsken J, et al: Molecular mechanisms leading to cell junction, cadherin, deficiency in invasive carcinomas. Semin Cancer Biol 4:231-239, 1993.
Choi BH, Holt JT, McDonald JV: Occult malignant astrocytoma of pons with extracranial metastasis to bone prior to craniotomy. Acta Neuropathol Berl 54:269-273, 1981.
Dolman CL: Lymph node metastasis as first manifestation of glioblastoma. J Neurosurg 41:607-609, 1974.
Farrier SE, Agosti S, Morgan M, et al: Metastatic ependymoma manifested by pancytopenia. South Med J 87:1262-1263, 1994.
Friedlander DR, Zagzag D, Shiff B, et al: Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor type and grade and involves alpha V and beta 1 integrins. Cancer Res 56:1939-1947, 1996.
Hoffman HJ, Duffner PK: Extraneural metastases of central nervous system tumors. Cancer 56:1778-1782, 1985.
Hulbanni S, Goodman PA: Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. Cancer 37:1577-1583, 1976. 10 Janisch W, Schreiber D, Guthert H: Neuropathologie – Tumoren des Nervensystems. Fischer, Stuttgart – New York, 1988. 11. Kung PC, Lee JC, Bakay L: Vascular invasion by glioma cells in man: an electron microscopic study. J Neurosurg 31:339-345, 1969. 12. Liwnicz BH, Rubinstein LJ: The pathways of extraneural spread in metastasizing gliomas: A report of three cases and critical review of the literature. Human Pathology 10:453-467, 1979. 13. Lossinsky AS, Mossakowski MJ, Pluta R, et al: Intercellular adhesion molecule-1, ICAM-1, upregulation in human brain tumors as an expression of increased blood-brain barrier permeability. Brain Pathol 5:339-344, 1995. 14. Mavroudis C, Townsend JJ, Wilson CB: A metastasizing ependymoma of the cauda equina. J Neurosurg 47:771-775, 1977. 15. McComb JG: Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg 59:369-383, 1983. 16. Mork SJ, Loken AC: Ependymoma: a follow-up study of 101 cases. Cancer 40:907-915, 1977. 17. Morris DM, Steinert HR, Wiernik PH: Ineffectiveness of chemotherapy in patients with metastatic ependymoma of the cauda equina. J Surg Oncol 22:33-36, 1983. 18. Newton HB, Henson J, Walker RW: Extraneural metastases in ependymoma. J Neurooncol 14:135-142, 1992. 19. Newton HB, Rosenblum MK, Walker RW: Extraneural metastases of infratentorial glioblastoma multiforme to the peritoneal cavity. Cancer 69:2149-2153, 1992. 20. Oehmichen M, Wietholter H, Gruninger H, et al: Destruction of intracerebrally applied red blood cells in cervical lymph nodes. Experimental investigations. Forensic Sci Int 21:43-57, 1983. 21. Oehmichen M, Gruninger H, Wietholter H, et al: Lymphatic efflux of intracerebrally injected cells. Acta Neuropathol Berl 45:61-65, 1979. 22. Pasquier B, Le Marc Hadour F, Dieny A, et al: Diffuse bone metastases. Cancer 68:2490-2491, 1991. 23. Paterson RJ Jr, Campbell WG Jr, Parsons H: Ependymoma of the cauda equina with multiple visceral metastases. J Neurosurgery 18:145-150, 1961. 24. Rubinstein LJ, Logan WJ: Extraneural metastases in ependymoma of the cauda equina. J Neurol Neurosurg Psychiatry 33:763-770, 1970. 25. Schreiber D, Schneider J, Heller T, et al: Intrakranielles Ependymom mit extra-neuralen Metastasen. Zentralbl Allg Pathol Pathol Anat 135:57-64, 1989. 26. Schroder R, Lorenzen J, Ostertag H, et al: Extraneurale Metastasierung von Hirn- und Ruckenmarktumoren. Bericht uber 2 Falle. Pathologe 16:223-229, 1995. 27. Schweitzer JS, Batzdorf U: Ependymoma of the cauda equina region: diagnosis, treatment, and outcome in 15 patients. Neurosurgery 30:202-207, 1992. 28. Sevick RJ, Johns RD, Curry BJ: Primary spinal primitive neuroectodermal tumor with extraneural metastases. Am J Neuroradiol 8:1151-1152, 1987. 29. Sharman KD: A metastasizing ependymoma of the cauda equina. Indian J Med Sci 10:639-641, 1956. 30. Sgouros S, Malluci CL, Jackowski A: Spinal ependymomas. The value of postoperative radiotherapy for residual disease control. Br J Neurosurg 10:559-566, 1996. 31. Sonneland PR, Scheithauer BW, Onofrio BM: Myxopapillary ependymoma. A clinico-pathologic and immunocytochemical study of 77 cases. Cancer 56:883-893, 1985. 32. Streit M, Schmidt R, Hilgenfeld RU, et al: Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. Recent Results Cancer Res 142:19-50, 1996. 33. Vanneste JLA: Subacute bilateral malignant exophtalmus due to orbital medulloblastoma metastases. Arch Neurol 40:441-443, 1983. 34. Weiss L: A metastasizing ependymoma of the cauda equina. Cancer 8:161-171, 1955. 35. Wight DG, Holley KJ, Finbow JA: Metastasizing ependymoma of the cauda equina. J Clin Pathol 26:929-935, 1973. 36. Willis RA: The spread of tumors in the human body, 2th ed, Mosby, St Louis, 1952.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 56
EP 60
PG 5
ER
PT J
AU Rabczynsky, J
Ziolkowski, P
AF Rabczynsky, Jerzy
Ziolkowski, Piotr
TI Primary Endometrioid Carcinoma of Fallopian tube
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Fallopian tube carcinoma; endometrioid carcinoma; histology; immunohistology; p53 protein; c-erbB-2
ID Fallopian tube carcinoma; endometrioid carcinoma; histology; immunohistology; p53 protein; c-erbB-2
AB Twenty cases of primary Fallopian tube endometrioid carcinoma (PFTEC) are presented in the paper. This accounts for 42.5% of all histologic forms of primary Fallopian tube carcinoma (PFTC) found in our Department. The youngest patient was 38, and the oldest 68 years (mean: 56 years). Seven patients were nulliparas. Only two cases were bilateral. According to FIGO staging, 13 cases were evaluated as stage I, 4 as II, and 3 as stage III. Due to the histologic grading, 8 tumors were classified as well, 7 as moderately, and 5 as poorly differentiated. In the time of preparation of the manuscript, 12 women were still alive, 2 of them with recurrent disease. The follow-up of patients without recurrence ranged from 4 to 120 months (median: 63). Eight patients had died (survival time: from 4 to 65 months; median: 26). Metastases were found in 8 patients, especially to ovaries. In 14/20 cases of PFTEC various forms of tubal wall invasion were observed. Blood or lymphatic vessels involvement was found in 9 patients. Six out of them had died and one is alive with the symptoms of disease. Immunohistochemical detection of the mutant form of p53 protein and oncogene product, c-erbB-2, was studied in 17 cases. Nine patients exhibited simultaneous p53 protein accumulation and c-erbB-2 expression. 2/9 of these patients are alive with recurrent tumors and 4/9 died. Endometrioid carcinoma of the Fallopian tube can be characterized by a tendency to superficial invasion of tubal wall and in a half of the cases by invasion of vessels. The majority of these tumors were diagnosed at an early stage tumors.
C1 [Rabczynsky, Jerzy] Wroclaw Medical University, Department of Pathology, ul. Marcinkowskiego 1, 50-386 Wroclaw, Poland.
[Ziolkowski, Piotr] Wroclaw Medical University, Department of Pathology, ul. Marcinkowskiego 1, 50-386 Wroclaw, Poland.
RP Ziolkowski, P (reprint author), Wroclaw Medical University, Department of Pathology, 50-386 Wroclaw, Poland.
CR Barakat RR, Rubin SC, Saigo PE, et al: Cisplatin-based combination chemotherapy in carcinoma of the fallopian tube. Gynecol Oncol 42:156-160, 1991.
Benedet JL, White GW, Fairey RN, et al: Adenocarcinoma of the Fallopian tube. Experience with 41 patients. Obstet Gynecol 50:654-657, 1977.
Dembo AJ, Davy M, Stenwig AF, et al: Prognostic factors in patients with stage I epithelial ovarian cancer. Obstet Gynecol 75:263-273, 1990.
Eltabbakh GH, Belinson JL, Kennedy AW, et al: p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer 80:892-898, 1997.
Hellstrom AC, Silfversward C, Nilsson B, et al: Carcinoma of the Fallopian tube. A clinical and histopathologic review. The Radiumhemmet series. Int J Gynecol Cancer 4:395-400, 1994.
Hu CY, Taymor ML, Hertig AT: Primary carcinoma of the Fallopian tube. Am J Obstet Gynecol 59:58-67, 1950.
Jereczek B, Jassem J, Kobierska A: Primary cancer of the Fallopian tube. Report of 26 patients. Acta Obstet Gynecol Scand 75:281-286, 1996.
Kojs Z, Urbanski K, Karolewski K, et al: Pierwotny rak jajowodu. Analiza 32 przypadkow. Gin Pol 67:612-614, 1996.
Koonings PP, Campbell K, Mishell DR, et al: Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol 74:921-926, 1989.
Lacy MQ, Hartmann LC, Keeney GL, et al: c-erbB-2 and p53 expression in Fallopian tube carcinoma. Cancer 75:2891-2896, 1995.
Levesque MA, Katsaros D, Yu H, et al: Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma. Cancer 75:1327-1338, 1995.
Lukes AS, Kohler MF, Pieper CF, et al: Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 73:2380-2385, 1994.
Mittal KR, Barwick KW: Diffusely infiltrating adenocarcinoma of the endometrium. A subtype with poor prognosis. Am J Surg Pathol 12:754- 758, 1988.
Navani SS, Alvarado-Cabbero I, Young RH, et al: Endometrioid carcinoma of the Fallopian tube: a clinicopathologic analysis of 26 cases. Gynecol Oncol 63:371-378, 1996.
Nordin AJ: Primary carcinoma of the Fallopian tube: a 20-year literature review. Obstet Gynecol Surv 49:349-361, 1994.
Peters WA, Andersen WA, Hopkins MP, et al: Prognostic features of carcinoma of the Fallopian tube. Obstet Gynecol 71:757-762, 1988.
Poulsen HE, Taylor CW, Sobin LH: Histological typing of female genital tract tumors.WHO Geneva 1975, 74-77.
Rabczynski J, Ziokowski P, Kowalski P, et al: Primary carcinoma of the fallopian tube – clinico-morphological review of 41 cases. Med Sci Monit 1998, in press).
Rorat E, Wallach RC: Endometrioid carcinoma of the Fallopian tube: pathology and clinical outcome. Int J Gynecol Obstet 32:163-167, 1990.
Rosen A., Klein M., Lahousen M., et al: Das primare tubenkarzinom – eine oesterreichische multizenterstudie. Geburtsh u Frauenheilk 53:321- 325, 1993.
Salvesen HB, Akslen LA, Albrektsen G, et al: Poorer survival of nulliparous women with endometrial carcinoma. Cancer 82:1328-1333, 1998.
Schiller HM, Silverberg SG: Staging and prognosis in primary carcinoma of the Fallopian tube. Cancer 28:389-395, 1971.
Scully RE, Bonfiglio TA, Kurman RJ, et al: Histological typing of female genital tract tumors 2nd ed., Springer Verlag. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong, Barcelona, Budapest, 1994, 15.
Serov SF, Scully RE, Sobin LH: International Histological Classification of Tumors, no. 9: Histological Typing of Ovarian tumors. WHO Geneva 1973.
Sedlis A: Primary carcinoma of the Fallopian tube. Obstet Gynecol Surv 16:209-226, 1961.
Tidy J, Mason WP: Endometrioid carcinoma of the ovary: a retrospective study. Brit J Obst Gynecol 95:1165-1169, 1988.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 61
EP 66
PG 6
ER
PT J
AU Nemes, B
Podder, H
Jaray, J
Dabasi, G
Lazar, L
Schaff, Zs
Sotonyi, P
Perner, F
AF Nemes, Balazs
Podder, Hemangshu
Jaray, Jeno
Dabasi, Gabriella
Lazar, Laura
Schaff, Zsuzsa
Sotonyi, Peter
Perner, Ferenc
TI Primary Hepatic Carcinoid in a Renal Transplant Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE renal transplant; hepatic carcinoid
ID renal transplant; hepatic carcinoid
AB There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases had malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression.
C1 [Nemes, Balazs] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
[Podder, Hemangshu] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
[Jaray, Jeno] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
[Dabasi, Gabriella] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
[Lazar, Laura] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sotonyi, Peter] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23., H-1082 Budapest, Hungary.
RP Nemes, B (reprint author), Semmelweis University, Department of Transplantation and Surgery, H-1082 Budapest, Hungary.
EM nemes@mailtrans.sote.hu
CR Alpert LI, Zak FG, Werthammer S, et al: Cholangiocarcinoma: a clinico-pathologic study of five cases with ultrastructural observations. Hum Pathol 5:709-728, 1974.
Andreola S, Lombardi L, Audisio RA, et al: A clinicopathologic study of primary hepatic carcinoids. Cancer 65:1211-1218, 1990.
Artopoulos JG, Destuni C: Primary mixed hepatocellular carcinoma with carcinoid characteristics. A case report. Hepatogastroenterology 41:442-444, 1994.
de Gennes JL, Kiortsis DN, Dairon F et al: Metastatic pulmonary carcinoma revealed by Cushing syndrome initially considered to have pituitary origin. Presse Med 24:1605-1617, 1995.
Godwin JD II: Carcinoid tumors: an analysis of 2837 cases. Cancer 36:560, 1975.
Goldblum JR, Lloyd RV: Primary renal carcinoid. Case report and review of the literature. Arch Pathol Lab Med 117:855-858, 1993.
Hayashi R, Hanyu N, Moriyama S: Efficacy of steroid therapy on liver metastasis of thymic carcinoid. Intern Med 33:45-47, 1994.
Himeno H, Yamamoto Y: Primary hormon producing hepatic tumor. Ryoikibetsu Shokogun Shirizu 7:511-514, 1995.
Holbrook RF, Koo K, Ryan JH: Resection of malignant primary liver tumors. Am J Surg 171:453-455, 1996.
Hsueh CI, Tan XD, Gonzalez Crussi F: Primary hepatic neuroendocrine carcinoma in a child. Morphologic, immuncytochemical and molecular biologic studies. Cancer 71:2660-2665, 1993.
Imaoka I, Sugimura K, Tamura K: Case report. MR imaging of a carcinoid tumor of the liver. Clin Radiol 47:287-289, 1993.
Inoue Y, Nakamura H, Mizumoto S, et al: Primary hepatic carcinoid with production of gastrin: a case report. Radiat Med 11:102-106, 1993.
Krishnamurthy SC, Dutta V, Pai SA, et al: Primary carcinoid tumor of the liver. Report of four resected cases. J Surg Oncol 62:218-221, 1996.
Lemaire LCJM, Pols HAP, Tilanus HW: Carcinoid tumor presenting as giant hepatic cyst. Br J Surg 82:133, 1995.
Marthur SK, Supe AN, Nagral SS, et al: Primary hepatic carcinoid, a case report). Indian J Gastroenterol 11(abstr.8), 1992.
Mauer CA, Baer HU, Dyong TH, et al: Carcinoid of the pancreas. Eur J Cancer 32A:1109-16, 1996.
Pi ZM: 20 rare primary hepatic malignant tumors. Chung Hua Chung Liu Tsa Chih 14:210-212, 1992.
Shima K, Ota G: Primary hepatic carcinoid. Ryoikibetsu Shokogun Shirizu 7:450-452, 1995.
Sioutos N, Virta S, Kessimian N: Primary hepatic carcinoid tumor. An electron microscopic and immunohistochemical study. Am J Clin Pathol 95:172-175, 1991.
Takayashu K, Muramatsu Y, Sakamoto M, et al: Findings in primary hepatic carcinoid tumor: US, CT, MRI and angiography. J Comp Ass Tomography 16:99-102, 1992.
Toth A, Alfoldy F, Jaray J, et al: Malignant tumors after renal transplantation. Acta Chir Hung 33:211-216, 1992.
Volte A, Iglicki F, Sevenet F, et al: Treatment of metastatic carcinoid with interferon alpha. Presse Med 25:63-67, 1996.
Yamashita Y, Takahashi M, Tsuji A, et al: Primary carcinoid tumor of the liver: a case report. J Comput Tomogr 10:313-317, 1986.
Yasoshima H, Uematsu K, Sakurai K, et al: Primary hepatic carcinoid. Acta Pathol Jpn 43:783-789, 1993.
Yu-Ping X, Ji-Yao Y: Primary neuroendocrine carcinoma of the liver. Ultrastruct Pathol 10:313-317, 1986.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 67
EP 69
PG 3
ER
PT J
AU Rath-Wolfson, L
Koren, R
Yaniv, E
Sadov, R
Gal, R
AF Rath-Wolfson, Lea
Koren, Rumelia
Yaniv, Eitan
Sadov, Rima
Gal, Rivka
TI A New Rapid Technique for the Fixation of Thyroid Gland Surgical Specimens
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE lymph node reveling solution; thyroid; fixation
ID lymph node reveling solution; thyroid; fixation
AB One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of ''Lymph Node Revealing Solution'' (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis.
C1 [Rath-Wolfson, Lea] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Koren, Rumelia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Yaniv, Eitan] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Sadov, Rima] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Gal, Rivka] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
RP Koren, R (reprint author), Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Pathology, Tel Aviv, Israel.
CR Koren R, Halpern M, Klein B, et al: A new rapid technique for the fixation of lymph nodes. Cell Vision 3:437-438, 1996.
Mc Marcus JFA, Mowry RW: Staining methods, histologic and histochemical. Harper & Brothers, New York, 1960, pp 19-21.
Lilie: Histologic technic and practical histochemistry. 3rd edition. Mc Grow-Hill Book Company, New York, 1965, pp 48-53.
Luna LG, ed): Manual of histologic staining methods of the Armed Forces Institute of Pathology. 3rd edition. McGraw-Hill Book Company, New York, pp 1968, 4-5.
Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex, ABC, in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody, PAP, procedures. J Histochem Cytochem 29:577-580, 1981.
Bugis SP, Young JEM, Archibald SD, et al: Diagnostic accuracy of fine-needle aspiration biopsy versus frozen section in solitary nodules. Am J Surg 152:411-416, 1986.
Rosai J: Ackerman’s surgical pathology. Thyroid gland frozen section. 8th edition. Mosby, St. Louis, 1996, pp 545-546.
Prophet EB, ed): Laboratory methods in histotechnology: Armed Forces Institute of Pathology, Washington DC. 1992.
Noguchi M, Furuya S, Takeuchi T, et al: Modified formalin and methanol fixation methods for molecular biological and morphological analyses. Pathol Int 47:685-691, 1997.
Horbin RW: Problems and artifacts of microwave accelerated procedures in neurohistotechnology and resolution. Methods 15:101-106, 1998.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 70
EP 72
PG 3
ER
PT J
AU Mikala, G
Xie, J
Berencsi, Gy
Kiss, Cs
Marton, I
Domjan, Gy
Valyi-Nagy, I
AF Mikala, Gabor
Xie, Jiuru
Berencsi, Gyorgy
Kiss, Csongor
Marton, Ildiko
Domjan, Gyula
Valyi-Nagy, Istvan
TI Human Herpesvirus 8 in Hematologic DiseasesFNT1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE HHV-8; tumorigenesis
ID HHV-8; tumorigenesis
AB Human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a new member of the gamma-herpesvirus family. It is an unusual herpesvirus in that it carries a large number of genes that encode oncoproteins or cell signaling proteins. In addition to being the causative agent of both HIV-associated and non-HIV-associated Kaposi's sarcoma this DNA tumor virus has been implicated in the pathogenesis of several diseases. These include multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), multicentric Castleman's disease (MCD), body cavity-based lymphoma (BCBL), and various other conditions such as sarcoidosis and pemphigus. While the causative role of the viral infection is fairly certain in the development of BCBL and multicentric Castleman's disease, HHV-8 may act through a different mechanism to induce plasma cell malignancies. It has been suggested - though the finding is still controversial - that infection of bone marrow stromal dendritic cells by HHV-8 might be a key factor in the etiology and pathogenesis of monoclonal gammopathies. The aim of this review is to provide a short introduction into the tumorigenic potential of HHV-8 as well as to detail the available data and possible mechanisms on the involvement of this virus in different hematologic diseases.
C1 [Mikala, Gabor] Imre Haynal University of Health Sciences, First Department of Internal Medicine, Szabolcs u. 35., H-1135 Budapest, Hungary.
[Xie, Jiuru] Bela Johan National Institute of HygieneBudapest, Hungary.
[Berencsi, Gyorgy] Bela Johan National Institute of HygieneBudapest, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of PediatricsDebrecen, Hungary.
[Marton, Ildiko] University Medical School of Debrecen, Department of StomatologyDebrecen, Hungary.
[Domjan, Gyula] Imre Haynal University of Health Sciences, First Department of Internal Medicine, Szabolcs u. 35., H-1135 Budapest, Hungary.
[Valyi-Nagy, Istvan] Imre Haynal University of Health Sciences, First Department of Internal Medicine, Szabolcs u. 35., H-1135 Budapest, Hungary.
RP Valyi-Nagy, I (reprint author), Imre Haynal University of Health Sciences, First Department of Internal Medicine, H-1135 Budapest, Hungary.
CR Agbalika F, Mariette X, Marolleau J-P, et al: Detection of human herpesvirus-8 DNA in bone marrow biopsies from patients with multiple myeloma and Waldenstroms macroglobulinemia. Blood 91:4393-4394, 1998.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 1999
VL 5
IS 1
BP 73
EP 79
PG 7
ER
PT J
AU Matolcsy, A
AF Matolcsy, Andras
TI Primary Effusional Lymphoma: A New Non-Hodgkin’s Lymphoma Entity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lymphoma; effusional
ID lymphoma; effusional
AB A distinct non-Hodgkin’s lymphoma (NHL) entity that grow in the body cavities as lymphomatous effusions in the absence of clinically identifiable tumor masses has been defined as primary effusional lymphoma (PEL). This lymphoma characterized by distinetive morphology, immunophenotype, genotype and association with Kaposi’s sarcoma-associated herpesvirus (KHSV)/human herpesvirus-8 (HHV-8) infection. In this minireview, the clinico-pathological and biological characteristics of PELs are summarized.
C1 [Matolcsy, Andras] University of Pecs, Department of Pathology, Szigeti ut 12, H-7624 Pecs, Hungary.
RP Matolcsy, A (reprint author), University of Pecs, Department of Pathology, H-7624 Pecs, Hungary.
EM amatolc@pathology.pote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 87
EP 89
PG 3
ER
PT J
AU Tanyi, J
Tory, K
Bankfalvi,
Shroder, W
Rath, W
Fuzesi, L
AF Tanyi, Janos
Tory, Kalman
Bankfalvi, Agnes
Shroder, Willibald
Rath, Werner
Fuzesi, Laszlo
TI Analysis of p53 Mutation and Cyclin D1 Expression in Breast Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; fibroadenoma; p53; mutation; cyclin D1; immunohistochemistry
ID breast cancer; fibroadenoma; p53; mutation; cyclin D1; immunohistochemistry
AB P53 and cyclin D1 are interacting regulatory genes and both are frequently altered in breast cancer. We analysed p53 mutation by SSCP and sequencing methods as well as p53 protein accumulation immunohistochemically in 34 consecutively operated breast tumors. None of 4 fibroadenomas revealed p53 mutation or p53 protein accumulation. Mutation of p53 was present in 7 carcinomas. Immunohistochemistry revealed accumulation of p53 protein in 6 carcinomas and there was a significant correlation between p53 mutation and protein accumulation. Overexpression of cyclin D1 protein was observed in 11 carcinomas by immunohistochemistry and no correlation was observed between cyclin D1 overexpression and p53 mutation or accumulation. Our data support the concept that the p53-cyclin D1 signal pathway and the cyclin D1 cascade are disregulated in breast cancer.
C1 [Tanyi, Janos] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross str. 27., H-1088 Budapest, Hungary.
[Tory, Kalman] Medical Faculty of the Technical University of Aachen, Department of PathologyAachen, Germany.
[Bankfalvi, Agnes] Medical Faculty of the Technical University of Aachen, Department of GynaecologyAachen, Germany.
[Shroder, Willibald] University of Munster, Department of PathologyMunster, Germany.
[Rath, Werner] University of Munster, Department of PathologyMunster, Germany.
[Fuzesi, Laszlo] Medical Faculty of the Technical University of Aachen, Department of PathologyAachen, Germany.
RP Tanyi, J (reprint author), Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, H-1088 Budapest, Hungary.
EM tanyi©noi1.sote.hu
CR Andersen TI, Holm R, Nesland JM, et al: Prognostic significance of TP53 alterations in breast carcinoma. Br J Cancer 68:540-548, 1993.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 90
EP 94
PG 5
ER
PT J
AU Nair, P
Nair, MK
Jayaprakash, GP
Pillai, MR
AF Nair, Prapid
Nair, M Krishnan
Jayaprakash, G Puthuveetil
Pillai, M Radhakrishna
TI Decreased Programmed Cell Death in the Uterine Cervix Associated with High Risk Human Papillomavirus Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HPV; apoptosis; cervical cancer
ID HPV; apoptosis; cervical cancer
AB The relationship between apoptosis, apoptosis regulatory proteins, cell proliferation and human papillomavirus infection during various phases of tumor progression in the uterine cervix was studied. Apoptosis was defined by morphological criteria and the TUNEL assay. Expression of p53, bcl-2, bax, cyclin D1, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant specific ELISA. Type of HPV infection was determined by PCR using type specific primers. Apoptosis showed significant negative correlation with increasing histological abnormality (p=0.0005). Higher tumor cell proliferation was associated with increasing histological abnormality (p=0.001 for Ki 67 and cyclin D1). There was significant correlation between histological grade and immunoreactivity of p53 (p=0.0001 ) and bcl-2 (p=0.0002). However, mutant p53 was expressed by only 12 of the 230 samples. Expression of bax and the bax/bcl-2 ratio showed an inverse correlation to histological grade (p=0.0003 and 0.0001, respectively). There was also an inverse correlation between extent of apoptosis and immunoreactivity of p53 (p=0.0001) and bcl-2 (p=0.0001). A significant positive correlation between expression of the bax protein and apoptosis was evident (p=0.0001). HPV infection significantly correlated to the extent of histological abnormality (p=0.0001). High risk HPV-E6 protein also showed this significant correlation (p=0.0002). There was an inverse correlation between apoptosis and HPV infection (p=0.0002). High risk HPV infection was associated with decreased apoptosis and also increased human cell proliferation. Lowest levels of bax/bcl-2 ratio was also associated with HPV 16 and 18 infection (p=0.0001). Modulation of apoptosis and apoptotic regulatory proteins by high risk HPV infection may be an important factor in the development of cervical cancer.
C1 [Nair, Prapid] Regional Cancer Centre, Division of Laboratory Medicine, 695011 Thiruvananthapuram, Kerala State, India.
[Nair, M Krishnan] Regional Cancer Centre, Division of Radiation OncologyThiruvananthapuram, India.
[Jayaprakash, G Puthuveetil] Regional Cancer Centre, Division of Radiation OncologyThiruvananthapuram, India.
[Pillai, M Radhakrishna] Regional Cancer Centre, Division of Laboratory Medicine, 695011 Thiruvananthapuram, Kerala State, India.
RP Pillai, MR (reprint author), Regional Cancer Centre, Division of Laboratory Medicine, 695011 Thiruvananthapuram, India.
EM mrpillaie@vsnl.com
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Wang TT: Differential effects of chemotherapeutic agents on bcl-2/bax apoptosis pathway in breast cancer cell. Proc Annu Meet Am Assoc Cancer Res 38:A769, 1997.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 95
EP 103
PG 9
ER
PT J
AU Dursun, A
Poyraz, A
Celik, B
Akyol, G
AF Dursun, Ayse
Poyraz, Aylar
Celik, Betul
Akyol, Gulen
TI Expression of c-erbB-2 Oncoprotein in Gastric Carcinoma: Correlation with Histopathologic Characteristics and Analysis of Ki-67
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-erbB-2; Ki-67; gastric carcinomas
ID c-erbB-2; Ki-67; gastric carcinomas
AB Amplification and overexpression of the c-erbB-2 gene has been demonstrated in several tumors and thought to be important determinants of biologic behaviors of carcinomas. In this study, correlation between c-erbB-2 expression und histopathologic parameters, including proliferative activity of gastric carcinomas was evaluated. Paraffin-embedded tissue sections from 62 patients who underwent curative resection of gastric carcinoma were analyzed immunohistochemically for the expression of c-erbB-2 and Ki-67. Strong membrane staining for c-erbB-2 was detected in 11 of 62 gastric carcinomas (17,7%) and no positive reaction was evident in noncancerous tissue. The incidence of c-erbB-2 pos- itivity in intestinal type carcinomas (24,3%) washigher than that of diffuse type carcinomas (4,76%). Positive staining for c-erbB-2 was present in one of the 9 (11,1%) early gastric carcinomas and 10 of 53 (18,8%) advanced gastric carcinomas. However, no statistically significant relationships were found between c-erbB-2 expression and histopathologic type, depth on invasion, the tumor size or lymph node metastases. Among the metastatic lymph nodes, 3 were positively stained with c-erbB-2 whereas the primary tumors of two cases had been found to be negative. Additionally, no correlation was found between c-erbB-2 reactivity and proliferative activity of carcinoma cells. The results suggest that expression of c-erbB-2 protein may occur selectively in intestinal type of gastric carcinomas. However, c-erbB-2 expression is not a reliable marker of malignant potential in gastric carcinomas.
C1 [Dursun, Ayse] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8, Mebusevleri Tandogan, 06580 Ankara, Turkey.
[Poyraz, Aylar] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8, Mebusevleri Tandogan, 06580 Ankara, Turkey.
[Celik, Betul] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8, Mebusevleri Tandogan, 06580 Ankara, Turkey.
[Akyol, Gulen] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8, Mebusevleri Tandogan, 06580 Ankara, Turkey.
RP Dursun, A (reprint author), Gazi University Faculty of Medicine, Department of Pathology, 06580 Ankara, Turkey.
CR Chariyalertsak S, Sugano K, Ohkura H, et al: Comparison of c-erbB-2 oncoprotein expression in tissue and serum of patients with stomach cancer. Tumor Biol 15:294-303, 1994.
Chen BF, Marrogi AJ, Freeman SM, et al: Gastric carcinoma recept issues in prognostic factors. J Lou State Med Soc 147:138-145, 1995.
Falck VG, Gullick WJ: C-erbB-2 oncogene product staning in gastric adenocarcinoma: An immunohistochemical study. J. Pathol 159:107-111, 1989.
Flejou JF, Paraf F, Muzeau F, et al: Expression of c erb B-2 oncogene product in Barrett’s adenocarcinoma: Pathological and prognostic correlations. J Clin Pathol 47:23-26, 1994.
Kameda T, Yasui W, Yoshida K, et al: Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification. Cancer Res 50:8002- 8009, 1990.
Lauren P: The two histological main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma. Acta Pathol Microbiol Scand 64:31-49, 1965.
Lee EY, Cibull ML, Strodel WE, et al: Expression of HER-2/neu oncoprotein and epidermal growth factor receptor and prognosis in gastric carcinoma. Arch Patol Lab Med 118:235-239, 1994.
Lemoine NR, Jain S, Silvestre F, et al: Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br J Cancer 64:79-83, 1991.
Mizutani T, Onda M, Tokunaga A, et al: Relationship of c-erbB- 2 protein expression and gene amplification to invasion and metastasis in human gastric cancer. Cancer 72:2083-2088, 1993.
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Orita H, Maehara Y, Emi Y, et al: C-erbB-2 expression is predictive for lymphatic spread of clinical gastric carcinoma. Hepatogastroenterology 44:294-298, 1997.
Tsugawa K, Fushida S, Yonemura Y: Amplification of the c-erbB-2 gene in gastric carcinoma: Correlation with survival. Oncology 50:418-425, 1993.
Uchino S, Tsuda H, Maruyama K, et al: Overexpression of c-erbB-2 protein in gastric cancer. Cancer 72:3179-3184, 1993.
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Yonemura Y, Ninomiya I, Ohoyama S, et al: Expression of c-erbB-2 oncoprotein in gastric carcinoma. Cancer 67:2914-2918, 1991.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 104
EP 106
PG 3
ER
PT J
AU Karabelyos, Cs
Dobozy, O
Szalai, Cs
Klenjanszki, K
Varju, K
Hadhazi,
Kiss,
Fulop, KA
Madarasz, B
Falus, A
AF Karabelyos, Csaba
Dobozy, Otto
Szalai, Csaba
Klenjanszki, Katalin
Varju, Kornelia
Hadhazi, Akos
Kiss, Arpad
Fulop, Kristof Andras
Madarasz, Balint
Falus, Andras
TI Elevated Hepatic Glucocorticoid Receptor Expression During Liver Regeneration in Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glucocorticoid receptor; liver; regeneration; monoclonal antibody; mRNA
ID glucocorticoid receptor; liver; regeneration; monoclonal antibody; mRNA
AB In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5–168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, between 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.
C1 [Karabelyos, Csaba] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Dobozy, Otto] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Szalai, Csaba] Heim Pal Children's HospitalBudapest, Hungary.
[Klenjanszki, Katalin] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Varju, Kornelia] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Hadhazi, Akos] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Kiss, Arpad] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Fulop, Kristof Andras] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Madarasz, Balint] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
[Falus, Andras] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4.Budapest, Hungary.
RP Falus, A (reprint author), Semmelweis University, Department of Genetics, Cell and Immunobiology, Budapest, Hungary.
EM faland@net.sote.hu
CR Apostolakos MJ, Schuermann WH, Frampton MW, et al: Measurement of gene expression by multiplex competitive polymerase chain reaction. Anal Biochem 213:277-284, 1993.
Berki T, Kumanovics G, Kumanovics A, et al: Production and flow cytometric application of a monoclonal anti-glucocorticoid receptor antibody. J Immun Meth 214:19-27, 1998.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidium thyocyanate-phenol-chloroform extraction. Anal Biochem 162:156-159, 1987.
Cressman DE, Greenbaum LE, DeAngelis RA, et al: Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274:1379-1383, 1996.
Dobozy O, Csaba G, Inczefi-Gonda A, et al: Impact of a single insulin treatment, imprinting, applied during liver regeneration on hepatic insulin receptor development, blood glucose level and liver function parameters in adult rats. Acta Phys Hung 79:331-338, 1992.
Golding M, Sarraf CE, Lalani EN, et al: Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver. Hepatology 4 Pt 1:1243-1253, 1995.
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Iimuro Y, Nishiura T, Hellerbrand C, et al: NFkappaB prevents apoptosis and liver dysfunction during liver regeneration. J Clin Invest 101:802-811, 1998.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 107
EP 109
PG 3
ER
PT J
AU Pacor, S
Gagliardi, R
Spessotto, P
Zabucchi, G
Sava, G
AF Pacor, Sabrina
Gagliardi, Renato
Spessotto, Paola
Zabucchi, Giuliano
Sava, Gianni
TI Paracrine Effects of IL-4 Transfection on TS/A Adenocarcinoma Cells Mediate Reduced In Vivo Growth
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB The in vitro/in vivo growth capacity and phenotype of TS/A and the IL4-transfected TS/A-IL4 cell lines were studied by cell cycle analysis, expression of ICAM-1/CD54, transferrin receptor/CD71 and E-cadherin and by histology of the primary tumors. TS/A-IL4, unlike the TS/A line, shows in vitro a marked increase in the fibroblastoid cell type and a decreased E-cadherin expression. Administration of conditioned medium containing IL4 obtained from the TS/A-IL4 cell line, stimulates CD54 expression in the TS/A cell line. TS/A-IL4 tumors grow more slowly in vivo and are ultimately rejected. These processes are accompanied by a marked increase in collagen and extracellular matrix proteins and increased recruitment and degranulation of mast cells. The paracrine effect of IL4, released by the transfected tumor cells, might be responsible for the reduced in vivo growth of the TS/A cell line in the presence of TS/A-IL4 cells.
C1 [Pacor, Sabrina] University of Trieste, Department of Biomedical Sciences, via L. Giorgieri 7-9, 34127 Trieste, Italy.
[Gagliardi, Renato] Institutes of Biological Research, Callerio FoundationTrieste, Italy.
[Spessotto, Paola] Institutes of Biological Research, Callerio FoundationTrieste, Italy.
[Zabucchi, Giuliano] University of Trieste, Department of Physiology and PathologyTrieste, Italy.
[Sava, Gianni] University of Trieste, Department of Biomedical Sciences, via L. Giorgieri 7-9, 34127 Trieste, Italy.
RP Sava, G (reprint author), University of Trieste, Department of Biomedical Sciences, 34127 Trieste, Italy.
EM gsava@fc.univ.trieste.it
CR Nanni P, De Giovanni C, Lollini PL et al: TS/A: a new metastasizing cell line from BALB/c spontaneous mammary adenocarcinoma. Clin Exp Metastasis 1:373-380, 1983.
Pericle F, Giovarelli M, Colombo MP et al: An efficient Th2- type memory follows CD8+ lymphocyte-driven and eosinophil- mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL4. J Immunol 153:5659- 5673, 1994.
Allione A, Consalvo M, Nanni P et al: Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin, IL)-2, IL-4, IL-6, IL-7, IL-10, Tumor Necrosis Factor a, Granulocyte-Macrophage Colony-stimulating Factor, and g-Interferon Gene or admixed with conventional adjuvants. Cancer Res 54:6022- 6026, 1994.
Colombo MP, Forni G: Immunotherapy I: Cyclosine gene transfer strategies. Cancer Met Rev 15:317-328, 1996.
Tepper RI, Pattengale PK, Leder P: Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503-512, 1989.
Tepper RI, Coffman RL, Leder P: An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 257:548-551, 1992.
Sosman JA, Bartemes K, Offord KP et al: Evidence for eosinophil activation in cancer patients receiving recombinant interleukin- 4: effects of interleukin-4 alone and following interleukin- 2 administration. Clin Cancer Res 1:805-812, 1995.
Brown MA, Hural J: Functions of IL-4 and control of its expression. Crit Rev Immunol 17:1-32, 1997.
Paul WE, Ohara J: B-cell stimulatory factor/interleukin 4. Annu Rev Immunol 5:429-435, 1987.
Sempowski GD, Derdak S, Phipps RP: Interleukin-4 and interferon- discordantly regulate collagen biosynthesis by functionally distinct lung fibroblast subsets. J Cell Physiol 167:290-296, 1996.
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Tiggelman AM, Boers W, Linthorst C, et al: Collagen synthesis by human liver, myo)fibroblasts in culture: evidence for a regulatory role of IL-1 beta, IL-4, TGFbeta and IFN gamma. J Hepatol 23:307-317, 1995.
Postlethwaite AE, Holnes MA, Katai H, et al: Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4. J Clin Invest 90:1479-1485, 1992.
Obiri NJ, Tandon N, Puri RK: Up-regulation of intercellular adhesion molecule 1, ICAM-1, on human renal cell carcinoma cells by interleukin-4. Int J Cancer 61:635-642, 1995.
Dustin MJ, Rothlein R, Bhan AK et al: Induction by IL-1 and interferon-g: tissue distribution, biochemistry and function of a natural adherence molecule, ICAM-1). J Immunol 137:245- 254, 1986.
DHHS, Guide for the care and use of laboratory animals DHHS publ., NIH Bethesda, MD, pp. 23-86, 1985.
Mc Bride WH, Economou JS, Syljuasen RG et al: The effects of cytokine gene transfer into tumors on host cell infiltration and regression. Anticancer Res; 16:1139-1144, 1996.
Kruger-Krasagakes S, Li W, Richter G et al: Eosinophils infiltrating interleukin-5 gene-transfected tumors do not suppress tumor growth. Eur J Immunol 23:992-995, 1993.
Noffz G, Quin Z, Kopf M, et al: Neutrophils but not eosinophils are involved in growth suppression of IL-4 secreting tumors. J Immunol 160:345-350, 1998.
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Natali P, Nicotra MR, Cavaliere R, et al: Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions. Cancer Res 50:1271-1278, 1990.
Tomita Y, Nishyiama T, Watanabe H, et al: Expression of intercellular adhesion molecule 1, ICAM-1, on renal cell cancer: possible significance in host immune responses. Int J Cancer 46:1001-1006, 1990.
Schardt C, Heymanns J, Schardt C, et al: Differential expression of the intercellular adhesion molecule 1, ICAM-1, in lung cancer cell lines of various histological types. Eur J Cancer 29A:2250-2255, 1993.
Steinbach F, Alexander J, Tanabe K, et al: Expression of cell adhesion molecules in an established and characterized new human renal cell cancer line, CCF-RC7. Urol Res 23:175-183, 1995.
Johnson JP, Stade BG, Holzmann B, et al: De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86:641-644, 1989.
Huang YW, Richardson J, Vitetta ES: Anti-CD54, ICAM-1, has antitumor activity in SCID mice with human myeloma cells. Cancer Res 55:610-616, 1995.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 110
EP 116
PG 7
ER
PT J
AU Tompa, A
Major, J
Jakab, GM
AF Tompa, Anna
Major, Jeno
Jakab, G Matyas
TI Is Breast Cancer Cluster Influenced by Environmental and Occupational Factors Among Hospital Nurses in Hungary?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ethylene oxide; exchange aberrations; genotoxicology monitoring; ionizing radiation; risk assessment
ID ethylene oxide; exchange aberrations; genotoxicology monitoring; ionizing radiation; risk assessment
AB An unusual cluster of 8 breast cancer and 8 other malignant tumor cases (ovarian, uterus, lung, colon and brain tumors and malignant melanoma) developed in a period of 12 years among 98 nurses exposed to ethylene oxide (EtOx) for 5–15 years in a unit using gas sterilizer in a hospital of the archiepiscopal city of Eger, Hungary. EtOx concentration in air samples of the working area varied from 5 to 150 mg/m3. The question was, if there was any causal relationship between the elevated incidence of breast cancer and the EtOx exposure, the other possibility was, that this cluster appeared accidentally. EtOx is a human carcinogen, however, no increased breast cancer incidence in EtOx-exposed subjects was reported in the literature. We followed up for two consecutive years the 27 non cancer patients, EtOx-exposed nurses and 11 unexposed hospital controls with the aid of a multiple genotoxicology monitor including chromosomal aberration, sister-chromatide exchange, HPRT point mutation and DNA repair studies. The results were compared with data from 30 local historical controls, 48 historical controls from Budapest, 14 hospital controls and 9 EtOx exposed nurses from Budapest. Significantly high chromosome aberration yields (especially chromosome type exchanges) were alike detected in EtOx-exposed and the two other control groups in Eger. These results could not be interpreted as a consequence of EtOx exposure only, since in the EtOx-exposed group from Budapest, beside an increased total aberration frequency, the obtained exchange type aberration yields were as low as the historical controls. A plausible explanation can be the natural low dose radioactivity (222Rn) of the local tap-water due to a specific geological situation in Eger. The spontaneous breast cancer incidence in Hungary doubled in the last 10 years compared with the previous 20 years (1960–1980), especially in Eger. The appearence of the high breast cancer incidence in the hospital of Eger indicates the combined effect of EtOx and a more common local etiologic factor, such as the naturally radioactive tap-water. However, since the reported studies did not involve the investigation either of the genetic predisposition, or the effects of other possible environmental, occupational, and/or life style confounding factors, further studies (partly in progress) are necessary to clarify the importance of these factors.
C1 [Tompa, Anna] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, H-1450 Budapest, Hungary.
[Major, Jeno] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, H-1450 Budapest, Hungary.
[Jakab, G Matyas] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, H-1450 Budapest, Hungary.
RP Tompa, A (reprint author), Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, H-1450 Budapest, Hungary.
EM okbi@elender.hu
CR WHO: World Health Statistics Annuals 1984-88. UN World Health Organisation, Geneva. 1988.
KSH: Demografiai Evkonyv 1970. Kozponti Statisztikai Hivatal, Budapest. 1972., in Hungarian).
KSH: Demografiai Evkonyv 1990. Kozponti Statisztikai Hivatal, Budapest. 1992., in Hungarian).
Wolff MS: Environmental exposures and breast cancer. In: Accomplishments in cancer research 1996., Eds: Fortner JG and Sharp PA), Lippincott – Raven Publ, Philadelphia-New York, 1997, pp. 136-144.
Tokunaga M, Land CE, Tokuoka S, et al.: Incidence of female breast cancer among atomic bomb survivors, 1950-1985. Radiation Res 138:208-223, 1994.
Tompa A, Major J, Jakab MG: Environmental genotoxicity and breast cancer risk in Hungary. Cancer Res. submitted for publication., 1999).
Hagmar L, Brogger A, Hansteen I-L, et al.: Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage. Cancer Res 54:2919-2922, 1994.
Bonassi S, Abbondandolo A, Camurri L, et al.: Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study. Cancer Genet Cytogenet 79:133-135, 1995.
Brusick DJ: Value of short-term mutagenicity tests in human population monitoring. In: Chemical mutagenesis, human population monitoring and genetic risk assessment. Progress in Mutation Research, Vol 3., Eds: Bora KC, Douglas GR and Nestmann ER), Elsevier Biomedical Press, Amsterdam-Oxford- New York, 1982, pp. 261-274.
Major J, Jakab MG, Tompa A: Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide: I. Chromosome aberrations, sister-chromatid exchanges, cell cycle kinetics, and UV-induced DNA synthesis in peripheral blood lymphocytes. Environ Molec Mutagen 27:84-92, 1996.
Agyagasi D: Balneological issues at Eger. Balneologia Gyogyfurdugy Gyogyidegenforgalom 1:3-16. 1993., in Hungarian, abstract in English).
IARC: Cancer: Causes, Occurrence and Control. Chapter 8. Radiation. In: IARC Scientific Publications No 100., Eds: Tomatis L, Aitio A, Day NE, Haseltine E, Kaldor J, Miller AB, Parkin DM, Riboli E), WHO, IARC, Lyon, 1990, pp. 157-158.
Tompa A, Major J, Jakab MG: Monitoring of benzene-exposed workers for genotoxic effects of benzene: Improved-workingcondition- related decrease in the frequencies of chromosomal aberrations in peripheral blood lymphocytes. Mutation Res 304:159-165, 1994.
Moorhead PS, Nowell PC, Mellman, et al.: Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 20:613-616, 1960.
Perry P, Wolff S: New Giemsa method for the differential staining of sister chromatids. Nature 258:121-125, 1974.
Carrano AV, Natarajan AT: Considerations for population monitoring using cytogenetic techniques. ICPEMC Publ. No. 14. Mutation Res 204:379-406, 1988.
Muller E, Bertok A: Az egri korhazban elfordult daganatos megbetegedesek - higienes viszonyok, konzekvenciak. Korhaz es Orvostechnika 33:17-22, 1995., in Hungarian).
Lerda D, Rizzi R: Cytogenetic studies of persons occupationally exposed to ethylene oxide. Mutation Res 281:31-37, 1992.
Major J, Jakab MG, Tompa A: Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide: II. Significance of environmental radon exposure in development of inceased exchange aberration frequencies obtained. Environ Molec Mutagen submitted for publication. 1999.
KSH: Demografiai Evkonyv 1996. Kozponti Statisztikai Hivatal, Budapest. 1998., in Hungarian).
Gombkoto G: Tumor morbidity and mortality among people living in settlements in the vicinity of town Eger. Egeszsegtudomany 39:154-171, 1995., in Hungarian, abstract in English)
Gombkoto G, Szeremi M: A Heves megyei lakossag megbetegedesi – halalozasi viszonyainak elemzese nemzetkozi es magyarorszagi osszehasonlitasban. NEKAP, Eger, 1997., in Hungarian).
Kertesz M: Data of the Air Quality Monitoring Network IV. 1996 – IX. 1996. Egeszsegtudomany 41:78-95, 1997., in Hungarian, abstract in English).
Norman SA, Berlin JA, Soper KA, et al.: Cancer incidence in a group of workers potentially exposed to ethylene oxide. Int J Epidemiol 24:276-284, 1995.
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Bojtor I, Gidali J, Feher I, et al.: Comparison of hematological parameters between “normal” population and residents consuming tap water of Ra content. Egeszsgtudomany 24:223-235, 1980., in Hungarian, abstract in English).
Koteles G, Nikl I, Szerbin P, et al.: Az egri egeszsegugyi problemak sugaregeszsegugyi vonatkozasai. Korhaz- es Orvostechnika 33:92-97, 1995., In Hungarian).
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 117
EP 121
PG 5
ER
PT J
AU Ozguroglu, M
Ersavasti, EG
Demir, G
Aki, H
Demirelli, F
Kanberoglu, K
Mandel, N
Buyukunal, E
Serdengecti, S
Berkarda, B
AF Ozguroglu, Mustafa
Ersavasti, Esen Gul
Demir, Gokhan
Aki, Hilal
Demirelli, Fuat
Kanberoglu, Kaya
Mandel, Nil
Buyukunal, Evin
Serdengecti, Suheyla
Berkarda, Bulent
TI Magnetic Resonance Imaging of Bone Marrow Versus Bone Marrow Biopsy in Malignant Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE malignant lymphoma; bone marrow biopsy; magnetic resonance imaging
ID malignant lymphoma; bone marrow biopsy; magnetic resonance imaging
AB Bone marrow involvement is a frequent finding in malignant lymphoma. Bone marrow biopsy of the posterior iliac crest is routinely performed for staging. Abnormal magnetic resonance imaging (MRI) signals of bone marrow was also reported to be indicative of bone marrow involvement. This study included 60 patients with malignant lymphoma. Unilateral bone marrow biopsy of the posterior iliac crest was performed. MRI of lumbar spine was studied within 24 hours of bone marrow biopsy. 22 healthy controls were used for the detection of MRI objectivity during visual evaluation. In 83% of patients (50/60), biopsy and MRI results agreed completely. In two patients, histologic sections failed to show any evidence of bone marrow involvement despite abnormal MRI signals suggestive of involvement. In three patients, MRI was completely normal despite biopsy proven bone marrow infiltration. False negativity (3/60) and false positivity (2/60) rates were very low. Negative biopsy findings with positive or equivocal MRI results should not exclude bone marrow involvement and needs further evaluation with bilateral or guided biopsy. Thus, we conclude that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.
C1 [Ozguroglu, Mustafa] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Ersavasti, Esen Gul] Cerrahpasa Medical School, Istanbul University, Department of RadiologyIstanbul, Turkey.
[Demir, Gokhan] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Aki, Hilal] Istanbul Medical Faculty, Department of PathologyIstanbul, Turkey.
[Demirelli, Fuat] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Kanberoglu, Kaya] Cerrahpasa Medical School, Istanbul University, Department of RadiologyIstanbul, Turkey.
[Mandel, Nil] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Buyukunal, Evin] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Serdengecti, Suheyla] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
[Berkarda, Bulent] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Yogurtcu Basi Sokagi, Akcira apt. 20/3ˆ, 81030 Istanbul, Dalyan-Fenerbahce, Turkey.
RP Ozguroglu, M (reprint author), Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, 81030 Istanbul, Turkey.
EM ozguroglu@superonline.com
CR Shipp MA, Mauch PM, Harris NL: Non-Hodgkin’s Lymphomas. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer, Principles and Practice of Oncology. 5th ed. Lippincott-Raven, Philadelphia, 1997:2165-2220.
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Bartl R, Frisch B, Burkhardt R, et al: Lymphoproliferations in the bone marrow: identification and evolution, classification and staging. J Clin Pathol 37:233-254, 1984.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 123
EP 128
PG 6
ER
PT J
AU Cserni, G
AF Cserni, Gabor
TI Estimating the Overlap Between Sentinel Lymph Nodes and Axillary Node Samples in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; axillary clearance; axillary sampling; staging
ID breast cancer; axillary clearance; axillary sampling; staging
AB Management of the axilla in breast cancer patients is a controversial issue. Axillary sampling and sentinel lymphadenectomy are both conservative surgical approaches which aim to stage the disease. These procedures target selective treatment of node-positive patients and seem to allow the omission of axillary clearance in node-negative ones. In this way, they reduce the rate of complications in an otherwise overtreated subset of patients. Forty consecutive patients with palpable T1 and T2 breast carcinoma underwent sentinel lymphadenectomy following mapping with Patent blue dye, with subsequent axillary clearance and excision of the tumor or mastectomy. Then the largest/firmest 3,4,5 and 6 nodes were selected from all the lymph nodes in order to model an axillary sample. It was suggested that these are the nodes that are the most likely to be included in the specimen during sampling, because of their size and consistency. The probability of the sentinel lymph nodes falling into the sample of the 3-6 largest/firmest nodes was calculated. The sentinel nodes predicted the axillary nodal status in 95%, while the samples of the largest 3, 4, 5 and 6 nodes were predictive in 95, 96, 98 and 98%, respectively. The two methods of evaluation displayed a considerable overlap, as the sentinel node would have been included in the 3–6 largest/firmest nodes in 79–92% of the cases, depending on the number of largest nodes evaluated. The overlap was greater after fine needle aspiration of the primary tumor. Although the two alternative staging procedures of 3, 4, 5 or 6 node sampling and sentinel lymphadenectomy with the vital blue dye technique cannot be simultaneously done without one influencing the other, and the first method was only modeled, the results suggest that there is a considerable overlap between the two; axillary sampling may often remove the sentinel lymph nodes.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
CR Albertini JJ, Lyman GH, Cox C, et al: Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 276:1818-1822, 1996.
American Joint Committee on Cancer: Breast. In: AJCC Cancer Staging Manual, Stn edition., Eds: Fleming ID, Cooper JS, Henson DE, et al), Lippincott Raven Publishers, Philadelphia, 1997, pp. 171-180.
Blichert-Toft M, Smola MG, Cataliotti L, et al: Principles and guidelines for 4 surgeons – management of symptomatic breast cancer. On behalf of the European Society of Surgical Oncology. Eur J Surg Oncol 23:101-109, 1997.
Borgstein P, Meijer S: Historical perspective of lymphatic tumour spread and the emergence of the sentinel node concept. Eur J Surg Oncol 24:85-89, 1998.
Cady B: Use of primary breast carcinoma characteristics to predict lymph node metastases. Editorial. Cancer 79:1856-1861, 1997.
Cady B, Stone MD, Schuler JG, et al: The new era in breast cancer: invasion, size and nodal involvement dramatically decreasing as a result of mammographic screening. Arch Surg 131:301-308, 1996.
Cserni G: Changing trends in lymph node recovery from axillary clearance specimens in breast cancer: possible implications for the quantitative axillary status from a 17 year retrospective study. Eur J Oncol 2:403-408, 1997.
Cserni G: Histopathologic basis for axillary sampling. Eur J Cancer 34(Suppl. 5):S 109, 1998.
Davidson T: Why I favour axillary node clearance in the management of breast cancer. Eur J Surg Oncol 21:5-7, 1995.
Davies GC, Millis RR, Hayward JL: Assessment of axillary lymph node status. Ann Surg 192:148-151, 1980.
Fisher CJ, Boyle S, Burke M, et al: Intraoperative assessment of nodal status in the selection of patients with breast cancer for axillary clearance. Br J Surg 80:457-458, 1993.
Forrest APM, Everington D, McDonald CC, et al: The Edinburgh randomized trial of axillary sampling or clearance after mastectomy. Br J Surg 82:1504-1508, 1995.
Forrest APM, Roberts MM, Cant E, et al: Simple mastectomy and pectoral node biopsy. Br J Surg 63:569-575, 1976.
Giuliano AE, Dale PS, Turner RR, et al: Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 180:700-704, 1995.
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Greenall MJ: Why I favour axillary node sampling in the management of breast cancer. Eur J Surg Oncol 21:2-5, 1995.
Harris JR, Osteen RT: Patients with early breast cancer benefit from effective axillary treatment. Breast Cancer Res Treat 5:17- 21, 1985.
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Mathiesen O, Carl J, Bonderup O, et al: Axillary sampling and the risk of erroneous staging of breast cancer. Acta Oncol 29:721-725, 1990.
Moore MP, Kinne DW: Axillary lymphadenectomy: a diagnostic and therapeutic procedure. J Surg Oncol 66:2-6, 1997.
Pigott J, Nichols MD, Maddox WA, et al: Metastases to the upper levels of axillary nodes in carcinoma of the breast and its implications for nodal sampling procedures. Surg Gynecol Obstet 158:255-259, 1984.
Ridings P, Bucknall TE: Modern trends in breast cancer therapy: towards less lymphoedema? Eur J Surg Oncol 24:21-22, 1998.
Statman R, Giuliano AE: The role of the sentinel lymph node in the management of patients with breast cancer. Adv Surg 30:209-221, 1997.
Steele RJC, Forrest APM, Gibson T, et al: The efficacy of lower axillary sampling in obtaining lymph node status in breast cancer; a controlled randomised trial. Br J Surg 72:368-369, 1985.
The Breast Surgeons Group of the British Association of Surgical Oncology: Guidelines for surgeons in the management of symptomatic breast disease in the United Kingdom. Eur J Surg Oncol 21(Suppl A):1-13, 1995.
Turner RR, Ollila DW, Krasne DL, et al: Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 226:271-276, 1997.
Veronesi U, Paganelli G, Galimberti V, et al: Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 349:1864-1867, 1997.
Veronesi U, Zurrida S, Galimberti V: Consequences of sentinel node in clinical decision making in breast cancer and prospects for future studies. Eur J Surg Oncol 24:93-95, 1998.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 129
EP 133
PG 5
ER
PT J
AU Sharma, S
Karak, KA
Singh, R
Mehta, SV
Sarkar, Ch
Schmitt, PH
AF Sharma, Suash
Karak, K Asis
Singh, Rajvir
Mehta, Singh Veer
Sarkar, Chitra
Schmitt, P Horst
TI A Correlative Study of Gliomas Using In Vivo Bromodeoxyuridine Labeling Index and Computer-aided Malignancy Grading
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gliomas; in vivo BrdU LI; malignancy classification; histologic grading; computer aided grading
ID gliomas; in vivo BrdU LI; malignancy classification; histologic grading; computer aided grading
AB An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of <1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI >5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.
C1 [Sharma, Suash] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Karak, K Asis] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Singh, Rajvir] All India Institute of Medical Sciences, Department of BiostatisticsNew Delhi, India.
[Mehta, Singh Veer] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Schmitt, P Horst] University of Heidelberg, Department of NeuropathologyHeidelberg, Germany.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarch@medinst.ernet.in
CR Burger PC, Scheithauer BW: Tumors of the central nervous system. Armed Forces Institute of Pathology, Washington, 1994.
Burger PC, Vogel FS, Green SB, et al: Glioblastoma multiforme and anaplastic astrocytoma : Pathologic criteria and prognostic implications. Cancer 56:1106-1111, 1985.
Daumos-Duport C, Scheithauer B, OFallen J, et al: Grading of astrocytomas: A simple and reproducible method. Cancer 62:2152-2165, 1988.
Dinda AK, Kharbanda K, Sarkar C, et al: In-vivo proliferative potential of primary human brain tumors : Its correlation with histological classification and morphological features. I. Gliomas. Pathology 25:4-9, 1993.
Dinda AK, Kharbanda K, Sarkar C, et al: In-vivo proliferative potential of primary human brain tumors: Its correlation with histological classification and morphological features. II. Nonglial Tumors. Pathology 25:10-14, 1993.
Gilles FH, Leviton A, Hedley-Whyte ET, et al: Childhood braintumor update. Hum Pathol 14:834-845, 1983.
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Hoshino T: A commentary on biology and growth kinetics of low grade and high grade gliomas. J Neurosurg 61:895-900, 1994.
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Hoshino T, Prados M, Wilson CB, et al: Prognostic implications of low bromodeoxyuridine labeling index of human gliomas. J Neurosurg 71:335-341, 1989.
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Sharma S, Karak AK, Sarkar C, et al: A grading study of gliomas using histologic morphometry and malignancy classification. J Neuro-Oncol 27:75-85, 1996.
Shapiro JR: Biology of gliomas: heterogenity, oncogenes, growth factors. Semin Oncol 133:4-15, 1986.
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Zulch KJ: Histological typing of tumors of central nervous system. International Histologic Classification of Tumors. World Health Organisation, Geneva, p14-50, 1979.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 134
EP 141
PG 8
ER
PT J
AU Moazzeni, MS
Amirzargar, AA
Shokri, F
AF Moazzeni, M Seyed
Amirzargar, Ali-Akbar
Shokri, Fazel
TI HLA Antigens in Iranian Patients with B-cell Chronic Lymphocytic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HLA antigens; chronic lymphocytic leukemia
ID HLA antigens; chronic lymphocytic leukemia
AB The frequency of HLA class-I and class-II antigens was investigated in 32 Iranian patients with B-cell chronic lymphocytic leukemia (B-CLL), using the microlymphocytotoxicity method. A significant increase in the HLA-B13 (P<0.01) and DR53 (P < 0.05) and a significant negative association with the A11 (P < 0.05), B35 (P < 0.05), Cw3 (P < 0.05), and DR1 (P < 0.02) antigens were observed in these patients, compared to the control normal population. These results suggest involvement of some HLA antigens in the multifactorial process of predisposition to B-CLL.
C1 [Moazzeni, M Seyed] School of Medical Sciences, Tarbiat Modarres University,, Department of ImmunologyTehran, Iran.
[Amirzargar, Ali-Akbar] Ahwaz University of Medical Sciences, Department of ImmunologyAhwaz, Iran.
[Shokri, Fazel] School of Medical Sciences, Tarbiat Modarres University,, Department of ImmunologyTehran, LR, Iran.
RP Shokri, F (reprint author), School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, Tehran, Iran.
CR Catovsky D, Foa R: The lymphoid leukemias. Buttenworth, London, 1990, pp. 73-111.
Cuttner J, Skerrett D, Rosina O, et al: Increased incidence of HLA antigen B35 in patients with chronic lymphocytic leukemia. Leukemia Res 18:565-567, 1994.
Dighiero G: Hypogammaglobulinemia and disordered immunity in CLL. In: Chronic lymphocytic leukemia, scientific advances and clinical developments., Ed: Chosen BD). Marcel Dekker, New York, 1993, pp. 167-180.
Dorak MT, Chalmers EA, Gaffney D, et al: Human major histocompatibility complex contains several leukemia susceptibility genes. Leuk Lymph 12:211-222, 1994.
Dorak MT, Owen G, Galbraith I, et al: Nature of HLA-associated predispoisition to childhood acute lymphoblastic leukemia. Leukemia 9:875-878, 1995.
Dorak MT, Machulla HKJ, Hentschel M, et al: Influence of the major histocompatibility complex on age at the onest of chronic lymphocytic leukemia. Int J Cancer 65:134-139, 1996.
Dyer PA, Ridway JC, Flanagan NG: HLA-A, B and DR antigens in chronic lymphocytic leukemia. Dis Marker 4:231-237, 1986.
Gale RP, Foon KA, Arbor A: Chronic lymphocytic leukemia. Recent advances in biology and treatment. Ann Intern Med 103:101-120, 1985.
Gunz FM: The epidemiology and genetics of the chronic leukemias. Clin Hematol 69:3-20, 1977.
Jones HP, Whittaker JA: Chronic lymphocytic leukemia: an investigation of HLA antigen frequencies and white cell differential counts in patients, relatives and controls. Leuk Res 15:543- 549, 1991.
Kilpatrick DC, Dewar AE, Stockdill G, et al: Histocompatibility antigen frequencies in patient with chronic lymphocytic leukemia: Possible identification of a subgroup with relatively benign disease. Scand J Haematol 33:391-396, 1984.
Khamesipur G, Mozdarani H. Shokri F: Cytogenetic analysis of malignant B-cells from Iranian patients with chronic lymphocytic leukemia. Irn J Med Sci 22:50-55, 1997.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 142
EP 145
PG 4
ER
PT J
AU Zalatnai, A
AF Zalatnai, Attila
TI Epidermal Growth Factor Receptor, Somatostatin and Bcl-2 in Human Pancreatic Tumor Xenografts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pancreas tumor; xenogaft; somatostatin; bcl-2
ID pancreas tumor; xenogaft; somatostatin; bcl-2
AB Xenografted human pancreatic tumors (5 ductal adenocarcinomas, 1 leiomyosarcoma, altogether 26 samples) were investigated about their immunohistochemical expression of epidermal growth factor receptor (EGFR), somatostatin (SS) and bcl-2 protein. The expression of the EGFR varied from tumor to tumor. One originally negative carcinoma became immunoreactive during passagings, one tumor has lost its early positive expression, and in 3 cancer lines a phenotypically constant pattern was seen. SS immunoreactivity was practically absent in all tumor samples. Concerning bcl-2 expression, different staining patterns were observed among the carcinomas, but the leiomyosarcoma has retained its strong positivity during xenograftings. In the PZX-5 carcinoma line that was originally negative, the one month Sandostatin treatment induced the strong expression of bcl-2 protein suggesting a development of an acquired resistance against programmed cell death in this tumor.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
CR Bell K, Bronner MP, Pasha T, et al: Expression of proliferating cell nuclear antigen in gastrointestinal tract lesions and its relationship to bcl-2 expression. Pathobiology 64:91-98, 1996.
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Lemoine NR, Hughes CM, Barton CM, et al: The epidermal growth factor receptor in human pancreatic cancer. J Pathol 166:7-12, 1992.
Makinen K, Hakala T, Lipponen P, et al: Clinical contribution of bcl-2, p53 and Ki-67 proteins in pancreatic ductal adenocarcinoma. Anticancer Res 18:615-618, 1998.
Matsuo H, Maruo T, Samoto T: Increased expression of Bcl-2 protein in human uterine leiomyoma and its up-regulation by progesterone. J Clin Endocrinol Metab 82:293-299, 1997.
Mejia MC, Navarro S, Pellin A, et al: Study of bcl-2 protein expression and the apoptosis phenomenon in neuroblastoma. Anticancer Res 18:801-806, 1998.
Nakanishi H, Ohsawa M, Naka N, et al: Immunohistochemical detection of bcl-2 and p53 proteins and apoptosis in soft tissue sarcoma: their correlations with prognosis. Oncology 54:238- 244, 1997.
Ohshio G, Suwa H, Imamura T, et al: An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic carcinomas. Scand J Gastroenterol 33:535-539, 1998.
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Saegusa M, Okayasu I: Bcl-2 is closely correlated with favorable prognostic factors and inversely associated with p53 protein accumulation in endometrial carcinomas: immunohistochemical and polymerase chain reaction/loss of heterozygosity findings. J Cancer Res Clin Oncol 123:429-434, 1997.
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Uegaki K, Nio Y, Inoue Y, et al: Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res 17:3841-3847, 1997.
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Vidal C, Rauly I, Zeggari M, et al: Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. Mol Pharmacol 46:97-104, 1994.
Vinter-Jensen L, Juhl CO, Teglbjaerg PS, et al: Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas. Gastroenterology 113:1367-1374, 1997.
Wada M, Doi R, Hosotani R, et al: Expression of bcl-2 and PCNA in duct cells after pancreatic duct ligation in rats. Pancreas 15:176-182, 1997.
Wada M, Hosotani R, Lee JU, et al: An exogenous cdk inhibitor, butyrolactone-1, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancreatic cancer cells. Anticancer Res 18:2559-2566, 1998.
Wang DG, Johnston CF, Buchanan KD: Oncogene expression in gastroenteropancreatic neuroendocrine tumors: implications for pathogenesis. Cancer 80:668-675, 1997.
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Witty JP, Jensen RA and Johnson AL: Expression and localization of Bcl-2 related proteins in human ovarian cancers. Anticancer Res 18:1223-1230, 1998.
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Zalatnai A, Bocsi J, Timar F, et al: Establishment and characterization of a new transplantable pancreatic cancer xenograft, PZX-5, in immunosuppressed mice. Internatl J Pancreatol 23:51-62, 1998.
Zalatnai A, Kovacs M, Flautner L, et al: Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow cytometric studies. Virchows Arch 432:469-472, 1998.
Zalatnai A, Schally AV: Treatment of the N-Nitrosobis/2-oxopropyl/ amine-induced pancreatic cancer in Syrian golden hamsters with D-Trp-6-LH-RH and somatostatin analog RC-160 microcapsules. Cancer Res 49:1810-1815, 1989.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 146
EP 151
PG 6
ER
PT J
AU Romics, I
AF Romics, Imre
TI A Case of Bilateral Testicular Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE testes; lymphoma
ID testes; lymphoma
AB Authors report on a 75-year-old man with bilateral testicular lymphoma. He complained of painless right testicular enlargement. Orchidectomy was indicated by ultrasound examination and the diagnosis (large cell, non-Hodgkin lymphoma B-cell origin) was established by histology and immunohistochemistry. Two months later, the left testis enlarged, orchidectomy was performed, and a lymphoma with identical histology was found. PET revealed retroperitoneal spread of the tumor. Irradiation (18 Gy) was applied. Three months later, because of gastric metastases of the lymphoma the patient underwent CVP and CAVP (Cyclophosphamide, Adriablastin, Vincristin, Prednisolone) chemotherapy. Despite of the repeated courses, eleven months after the primary diagnosis the patient died due to of multiple metastases.
C1 [Romics, Imre] Semmelweis University, Department of Urology, Ulloi ut 78/b, 1082 Budapest, Hungary.
RP Romics, I (reprint author), Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
CR Adolphs HD, Lindenfelser R, Steffens L, et al: Immunoblastic sarcoma with clinically primary manifestation in the testis, author’s transl). Urol Int 32:8-17, 1977.
Bach D, Weissbach L, Adolphs HD: Malignant lymphoma of the testis an urological or nonurological disease? Z Urol Nephrol 71:201-106, 1978.
Crellin AM, Hudson BV, Bennett MH, et al: Non-Hodgkins lymphoma of the testis. Radiother Oncol 27:99-106, 1993.
Bentley RC, Devlin B, Kaufman RE, et al: Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes. Hum Pathol 24:675- 678, 1993.
Read G: Lymphomas of the testis – results of tretment 1960-77. Clin Radiol 32:687-692, 1981.
Frang D, Czvalinga I, Nagy Z, et al: Bilateral testicular tumours. Acta Chir Acad Sci Hung 19:271-280, 1978.
Sussman EB, Hajdu SI, Lieberman PH, et al: Malignant lymphoma of the testis: a clinicopathologic study of 37 cases. J Urol 118:1004-1007, 1977.
Ito H, Fuse H, Hirano S, et al: Malignant lymphoma of the testis: report of two cases. Hinyokika Kiyo 43:599-603, 1997.
Swierz J, Zielinski H, Dabek A: Malignant lymphoma of both testes. Pol Merkuriusz Lek 2:181-182, 1997.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 152
EP 154
PG 3
ER
PT J
AU Elek, G
Slowik, F
Eross, L
Toth, Sz
Szabo, Z
Balint, K
AF Elek, Gabor
Slowik, Felicia
Eross, Lorand
Toth, Szabolcs
Szabo, Zerind
Balint, Katalin
TI Central Neurocytoma with Malignant Course
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE central neurocytoma; atypical central neurocytoma; glial and neuronal differentiation; ganglioglioma
ID central neurocytoma; atypical central neurocytoma; glial and neuronal differentiation; ganglioglioma
AB Central neurocytoma is a benign neuronal tumor of young adults in the lateral cerebral ventricles with characteristic X ray and light microscopic findings. In many respects typical central neurocytoma is reported below, with recurrence in the third month requiring reoperation. Death ensued in the fifth postoperative month. Subsequent histology proved progressive vascular proliferation and increasing, unusual glial differentiation of the neuronal tumor. At autopsy tumorous seeding blocked the liquor circulation. A thin tumorous layer covered the surface of all ventricles, the cerebellum and medulla oblongata. The GFAP positive cells out-numbered the synaptophysin positive ones. Increase of GFAP positivity and vascular proliferation of the central neurocytoma may be alarming signs suggesting a malignant course in addition to the other atypical features.
C1 [Elek, Gabor] Central Railway Hospital and Polyclinic, Department of Pathology, Pathology of MAV Hospital at Pest, Podmaniczky u 11, H-1062 Budapest, Hungary.
[Slowik, Felicia] National Institute of NeurosurgeryBudapest, Hungary.
[Eross, Lorand] Hospital of Hungarian Railways, Department of Neurosurgery and Dr Toth Zoltan FoundationBudapest, Hungary.
[Toth, Szabolcs] Hospital of Hungarian Railways, Department of Neurosurgery and Dr Toth Zoltan FoundationBudapest, Hungary.
[Szabo, Zerind] Hospital of Hungarian Railways, Department of Neurosurgery and Dr Toth Zoltan FoundationBudapest, Hungary.
[Balint, Katalin] National Institute of NeurosurgeryBudapest, Hungary.
RP Elek, G (reprint author), Central Railway Hospital and Polyclinic, Department of Pathology, H-1062 Budapest, Hungary.
CR Akimoto J, Itoh H, Itoh Y, et al: Histogenesis of central neurocytoma: an immunohistochemical and electronmicroscopic study of four cases. No Shinkei Geka 23:1083-1091, 1995.
Alleyne CH, Hunter S, Olson JJ, et al: Lipomatosus glioneurocytoma of the posterior fossa with divergent differentiation. Neurosurgery 42:639-643, 1998.
Barbosa DM, Balsitis M, Jaspan T, et al: Intraventricular neurocytoma: a clinical and pathological study of three cases. Neurosurgery 26:1045-1054, 1990.
Burger PC, Scheithauer BW: Tumors of the central nervous system. Atlas of tumor pathology, third series, AFIP, Fascicle 10:178-184 and 193-194, 1994.
Deimling A, Kleihues P, Saremaslani P, et al: Histogenesis and differentiation potential of central neurocytomas. Lab Invest 64:585-591, 1991.
Deimling A, Janzer R, Kleihues P, et al: Patterns of differentiation in central neurocytoma. Acta Neuropathol 79:473-479, 1990.
Dodds D, Nonis J, Mehta M, et al: Central neurocytoma: a clinical study of response to chemotherapy. J Neurooncol 34:279- 283, 1997.
Eng DY, DeMonte F, Ginsberg L, et al: Craniospinal dissemination of central neurocytoma. J Neurosurg 86:547-552, 1997.
Figarella-Branger D, Pellissier JF, Daumas-Duport C, et al: Central neurocytomas: critical evaluation of a small cell neuronal tumor. Am J Surg Pathol 16:97-106, 1992.
Fujimaki T, Matsuno A, Sasaki T, et al: Proliferative activity of central neurocytoma: doubling time, MIB-1 and bromodeoxyuridine labeling index. J Neurooncol 32:103-109, 1997.
Funato H, Inoshita N, Okeda R, et al: Cystic ganglioneurocytoma outside the ventricular region. Acta Neuropathol 94:95- 98, 1997.
Giangaspero F, Cenacchi G, Losi L, et al: Extraventricular neoplasms with neurocytoma features. Am J Surg Pathol 21:206- 212, 1997.
Hassoun J, Soylemezoglu F, Gambarelli D, et al:Central neurocytoma: a synopsis of clinical and histological features. Brain Pathol 3:297-306, 1993.
Horoupian DS, Shuster DL, Kaarsoo-Herrick M, et al: Central neurocytoma: one associated with a fourth ventricular PNET/medulloblastoma and the second mixed with adipose tissue. Hum Pathol 28:1111-1114, 1997.
Kim DG, Kim JS, Chi JG, et al: Central neurocytoma: proliferative potential and biological behavior. J Neurosurg 84:742- 747, 1996.
Kim DG, Paek SH, Kim IH, et al: Central neurocytoma: the role of radiation therapy and long term outcome. Cancer 79:1995- 2002, 1997.
Kim DH, Suh YL: Pseudopapillary neurocytoma of temporal lobe with glial differentiation. Acta Neuropathol 94:187-191, 1997.
Kubota T, Hayashi M, Kawano H, et al: Central neurocytoma: immunohistochemical and ultrastructural study. Acta Neuropathol 81:418-427, 1991.
Langford LA: Central nervous system noplasms: indications for electron microscopy. Ultrastruct Pathol 20:35-46, 1996.
Louis DN, Swearingen B, Linggood RM, et al: Central nervous system neurocytoma and neuroblastoma in adults. J Neurooncol 9:231-238, 1990.
Mineura K, Sasajima T, Itoh Y, et al: Blood flow and metabolism of central neurocytoma. Cancer 76:1224-1232, 1995.
Mrak RE: Malignant neurocytic tumor. Hum Pathol 25:747- 752, 1994.
Nishio S, Fujiwara S, Tashima T, et al: Tumors of the lateral ventricular wall, especially the septum pellucidum. Neurosurgery 27:224-230, 1990.
Nishio S, Takeshita I, Fukui M: Primary cerebral ganglioneurocytoma in an adult.Cancer 66:358-362, 1990.
Pal L, Santosh V, Gayathri N, et al: Neurocytoma/rhabdomyoma of the cerebellum. Acta Neuropathol 95:318-323, 1998.
Schild SE, Scheithauer BW, Haddock MG, et al: Central neurocytomas. Cancer 79:790-795, 1997.
Schweitzer JB, Davies KG: Differentiating central neurocytoma. J Neurosurg 86:534-546, 1997.
Sgouros S, Carey M, Aluwihare N, et al: Central neurocytoma: correlative clinicopathologic and radiologic analysis. Surg Neurol 49:197-204, 1998.
Soylemezoglu F, Scheithauer BW, Esteve J, et al: Atypical central neurocytoma. J Neuropathol Exp Neurol 56:551-556, 1997.
Tatter SB, Borges LF, Louis DN: Central neurocytomas of the cervical spinal cord. J Neurosurg 81:288-293, 1994.
Tomura N, Hirano H, Watanabe O, et al: Central neurocytoma with clinically malignant behavior. Am J Neuroradiol 18:1175- 1178, 1997.
Tsuchida T, Matsamuto M, Shirayama Y, et al: Neuronal and glial characteristics of central neurocytoma. Acta Neuropathol 91:573-577, 1996.
Yamamoto T, Komori T, Shibata N, et al: Multifocal neurocytoma/ gangliocytoma with extensive leptomeningeal dissemination in the brain and spinal cord. Am J Surg Pathol 20:363-370, 1996.
Yasargil MG, Ammon K, Deimling A, et al: Central neurocytoma: histopathological variants and therapeutic approaches. J Neurosurg 76:32-37, 1992.
Valdueza JM, Westphal M, Vortmeyer A, et al: Central neurocytoma: clinical, immunohistologic and biologic findings of a human neuroglial progenitor tumor. Surg Neurol 45:49-56, 1996.
Zentner J, Peiffer J, Roggendorf W, et al: Periventricular neurocytoma. Surg Neurol 38:38-42, 1992.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 155
EP 159
PG 5
ER
PT J
AU Blaker, H
Dragoje, S
Laissue, JA
Herwart, FO
AF Blaker, Hendrik
Dragoje, Susanne
Laissue, Jean-Albert
Herwart, F Otto
TI Pericardial Involvement by Thymomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE pericardium; thymoma; glomeruloid structures
ID pericardium; thymoma; glomeruloid structures
AB Thymomas are usually found in the anterior mediastinum, the normal location of the thymus. Involvement of the pericardium by thymic tumors is seen in invasive or metastasized thymoma. Very rarely, thymomas arise primarily in the pericardium. These tumors are believed to derive from thymic tissue which was misplaced in the pericardium during embryologic development. In contrast to patients with orthotopic thymoma who commonly suffer from paraneoplastic diseases, especially myasthenia gravis, patients with intrapericardial thymoma manifestations mainly have symptoms of congestive heart failure which are caused by local complications of tumor growth. In this study, we present two cases of thymoma involving the pericardium. Both tumors were polygonal-oval cell thymomas. In one of the cases diagnosis of an entirely intrapericardial thymoma was established by autopsy. In the other case, explorative thoracotomy revealed massive pericardial and pleural tumor manifestations. The latter tumor showed a peculiar histological pattern with multiple glomeruloid bodies, a finding reported only once for thymomas.
C1 [Blaker, Hendrik] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Dragoje, Susanne] University of Bern, Department of PathologyBern, Switzerland.
[Laissue, Jean-Albert] University of Bern, Department of PathologyBern, Switzerland.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
RP Blaker, H (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
EM hendrik_blaeker@krzmail.krz.uni-heidelberg.de
CR Burke A, Virmani R: Tumors of the heart and the great vessels. Third series, fascicle 16. Washington DC: Armed Forces Institute of Pathology, 1996.
Chow W-H, Chow T-C, Chiu S-W: Pericardial metastasis and effusion as the initial manifestation of of malignant thymoma: identification by cross-sectional echocardiography. Int J Cardiol 37:258-260, 1992.
Eglen DE: Pericardial based thymoma: diagnosis by fine needle aspiration. Indiana Med 79:526-528, 1986.
Gaudin PB, Rosai J: Florid vascular proliferation associated with neural and neuroendocrine neoplasms. Am J Surg Pathol 19:642-652, 1995.
Iliceto S, Quagliara D, Calabrese P, et al: Visualization of pericardial thymoma and evaluation of chemotherapy by two dimensional echocardiography. Am Heart J 107:605-606, 1984.
Loire R, Hellal H: Pericardites neoplastique. Etude par thoracotomie et biopsie daps 80 cas. Presse Med 22:244-248, 1993.
Marino M, Muller Hermelink HK: Thymoma and thymic carcinoma. Virch Arch [A] 407:119-149, 1985.
McAllister HA, Fenoglio JJ: Atlas of Tumor Pathology. Tumors of the cardiovascular system. Second series, fascicle 15. Washington DC: Armed Forces Institute of Pathology, 1978.
Mirra M, Zanella M, Bussani R, et al: Intrapericardial thymoma. Arch Pathol Lab Med 121:59-63, 1997.
Nishimura T, Kondo M, Miyazaki S, et al: Two-dimensional echocardiographic findings in cardiovascular involvement by invasive thymoma. Chest 81:752-754, 1982.
Russel DS, Rubinstein LJ: Pathology of tumors of the nervous system. Baltimore, MD: Williams and Wilkins, 1989.
Shimosato Y, Mukai K: Atlas of tumor pathology: Tumors of the mediastinum. Third series, fascicle 21. Washington DC: Armed Forces Institute of Pathology, 1997.
Venegas RJ, Sun NC: Cardiac tamponade as a presentation of malignant thymoma. Acta Cytol 32:257-262, 1988.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 1999
VL 5
IS 2
BP 160
EP 163
PG 4
ER
PT J
AU Larsen, KA
Gobert, C
AF Larsen, K Annette
Gobert, Celine
TI DNA Topoisomerase I in Oncology: Dr Jekyll or Mr Hyde?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE topoisomerase I; multifunctional proteins; oncogenesis; antitumor agents
ID topoisomerase I; multifunctional proteins; oncogenesis; antitumor agents
AB Mammalian DNA topoisomerase I is a multifunctional enzyme which is essential for embryonal development. In addition to its classical DNA nicking-closing activities which are needed for relaxation of supercoiled DNA, topoisomerase I can phosphorylate certain splicing factors. The enzyme is also involved in transcriptional regulation through its ability to associate with other proteins in the TFIID-, and possibly TFIIH-, transcription complexes, and is implicated in the recognition of DNA lesions. Finally, topoisomerase I is a recombinase which can mediate illegitimate recombination. A crucial reaction intermediate during relaxation of DNA is the formation of a DNA-topoisomerase I complex (the cleavable complex) where topoisomerase I is covalently linked to a 3’-end of DNA thereby creating a single stranded DNA break. Cleavable complexes are also formed in the vicinity of DNA lesions and in the presence of the antitumor agent, camptothecin. While formation of cleavable complexes may be necessary for the initial stages of the DNA damage response, these complexes are also potentially dangerous to the cell due to their ability to mediate illegitimate recombination, which can lead to genomic instability and oncogenesis. Thus the levels and stability of these complexes have to be strictly regulated. This is obtained by maintaining the enzyme levels relatively constant, by limiting the stability of the cleavable complexes through physical interaction with the oncogene suppressor protein p53 and by degradation of the topoisomerase I by the proteasome system. Emerging evidence suggest that these regulatory functions are perturbed in tumor cells, explaining at the same time why topoisomerase I activities so often are increased in certain human tumors, and why these cells are sensitized to the cytotoxic effects of camptothecins.
C1 [Larsen, K Annette] Institut Gustave-Roussy, Laboratory of Biology and Pharmacology of DNA Topoisomerases, 39, Rue Camille Desmoulins, 94805 Villejuif, Cedex, France.
[Gobert, Celine] Institut Gustave-Roussy, Laboratory of Biology and Pharmacology of DNA Topoisomerases, 39, Rue Camille Desmoulins, 94805 Villejuif, Cedex, France.
RP Larsen, KA (reprint author), Institut Gustave-Roussy, Laboratory of Biology and Pharmacology of DNA Topoisomerases, 94805 Villejuif, France.
EM aklarsen@igr.fr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 171
EP 178
PG 8
ER
PT J
AU Eerola, AK
Ruokolainen, H
Soini, Y
Raunio, H
Paakko, P
AF Eerola, Anna-Kaisa
Ruokolainen, Henni
Soini, Ylermi
Raunio, Hannu
Paakko, Paavo
TI Accelerated Apoptosis and Low Bcl-2 Expression Associated with Neuroendocrine Differentiation Predict Shortened Survival in Operated Large Cell Carcinoma of the Lung
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mcl-1; bax; bak; neuroendocrine differentiation; prognosis
ID Mcl-1; bax; bak; neuroendocrine differentiation; prognosis
AB In order to test the hypothesis that increased apoptotic activity is connected with neuroendocrine differentiation and low differentiation degree in large cell carcinoma (LCLC) and is regulated by bcl-2 family proteins, we analysed the extent of apoptosis and tumor necrosis and their relation to the expression of bcl-2, bax, bak and mcl-1 in 35 LCLCs, of which 20 were classified as large cell neuroendocrine lung carcinomas (LCNEC) and 15 as large cell non-neuroendocrine lung carcinomas (LCNNEC). The extent of apoptosis was determined by detecting and counting the relative and absolute numbers of apoptotic cells and bodies using in situ 3'-end labelling of the apoptotic DNA. The extent and intensity of expression of the bcl-2, bax, bak and mcl-1 proteins were studied by immunohistochemistry. Also the relative volume density of necrosis was evaluated and correlated with the other parameters. Finally, all the parameters were evaluated as prognostic markers and correlated with data on the survival of the patients. Relatively high apoptotic indices were seen in both tumor types (average for both 2.53%, range 0.09–27.01%). Significantly higher bcl-2 and bak indices were detected more often in LCNECs than in LCNNECs. Immunohistochemically detected bax, bcl-2 and bak expression was independent of apoptotic index in both tumor types, while there was a statistically significant positive association between mcl-1 expression and apoptotic index in LCNNEC but not in LCNEC. There was a statistically significant association between high apoptotic index and shortened survival in LCLC. However, no association was found between tumor stage and apoptosis. The patients with LCNEC and low bcl-2 protein expression had a significantly shorter survival time than those with high bcl-2 indices. There was also a clear association between shortened survival and necrotic LCNNEC. LCLCs show relatively high apoptotic activity, which is associated with shortened survival. The expression of bcl-2, bak and mcl- 1 is associated with neuroendocrine differentiation in LCLC. Finally, our results support some previous reports suggesting that bcl-2 expression in combination with some other markers involved in apoptosis and/or proliferation may be of prognostic value in cases of lung carcinoma with neuroendocrine differentiation.
C1 [Eerola, Anna-Kaisa] University of Oulu, Department of PathologyOulu, Finland.
[Ruokolainen, Henni] University of Oulu, Department of PathologyOulu, Finland.
[Soini, Ylermi] University of Oulu, Department of Pathology, Kajaanintie 52 D, FIN-90401 Oulu, Finland.
[Raunio, Hannu] University of Oulu, Department of Pharmacology and ToxicologyOulu, Finland.
[Paakko, Paavo] University of Oulu, Department of Pathology, Kajaanintie 52 D, FIN-90401 Oulu, Finland.
RP Paakko, P (reprint author), University of Oulu, Department of Pathology, FIN-90401 Oulu, Finland.
EM paavo.paakko@oulu.fi
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 179
EP 186
PG 8
ER
PT J
AU Tanyi, J
Tory, K
Rigo, J
Nagy, B
Papp, Z
AF Tanyi, Janos
Tory, Kalman
Rigo, Janos
Nagy, Balint
Papp, Zoltan
TI Evaluation of the Tyrosine Kinase Domain of the Met Proto-oncogene in Sporadic Ovarian Carcinomas*
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Met proto-oncogene; epithelial ovarian tumor; tyrosine kinase domain; mutation
ID Met proto-oncogene; epithelial ovarian tumor; tyrosine kinase domain; mutation
AB Most of the ovarian cancers originate from the ovarian surface epithelium derived from the coelomic mesothelium. The Met proto-oncogene encodes a transmembrane tyrosine kinase receptor (Met) that has the capacity to regulate cell proliferation and differentation and it is activated by hepatocyte growth factor. Trisomy of chromosome 7 and Met protein overexpression have been were observed in ovarian carcinomas, the papillary renal cancers and other solid tumors. Frequent mutations of Met proto-oncogene have been found in hereditary papillary renal cancer (HPRC) and most of the mutations are located in the tyrosine kinase domain. The aim of this study to perform a mutation analysis of exons 17–19 of Met proto-oncogene in epithelial ovarian tumors (EOTs). We have examined 24 tumor samples from patients, operated with EOTs. Mutation was detected in exon 18 in only one sample of 24 EOTs. Our results indicate that mutations located in the Met proto-oncogene is not a common event in EOT. It is not clear whether the mutation plays a role in the tumorigenesis or progression of EOT or not.
C1 [Tanyi, Janos] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross str. 27., H1088 Budapest, Hungary.
[Tory, Kalman] N-Gene R&DNew York, USA.
[Rigo, Janos] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross str. 27., H1088 Budapest, Hungary.
[Nagy, Balint] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross str. 27., H1088 Budapest, Hungary.
[Papp, Zoltan] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross str. 27., H1088 Budapest, Hungary.
RP Tanyi, J (reprint author), Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, H1088 Budapest, Hungary.
EM tanyi@noi1.sote.hu
CR Bergerheim USR, et al: Chromosomal gains and losses in sporadic and hereditary papillary renal carcinomas by comperative genomic hybridization. J Urol 155:543A, 1996.
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Chi-Ho Mok S, Bell DA, Knapp RC, et al: Mutation of K-ras protooncogene in human ovarian tumors of borderline malignancy. Cancer Res 53:1489-1492, 1993.
Di Renzo MF, Olivero M, Katsaros D, et al: Overexpression of the Met/HGF receptor in ovarian cancer. Int J Cancer 58:658- 662, 1994.
Di Renzo MF, Olivero M, Ferro S, et al.: Overexpression of the c-Met/Hgf receptor gene in human thyroid carcinomas. Oncogene 7:2549-53, 1992.
Ebert M, Yokohama M, Friess H, et al: Coexpression of the c- Met proto-oncogene and hepatocyta growth factor in human pancreatic cancer. Cancer Research 54:5775-5778, 1994.
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Sonnenberg E, Meyer D, Weidner KM, rt al: Scatter factor/hepatocyte growth factor and its receptor, the c-Met tyrosine, can mediate a signal exchange between mesenchyme and epithelial cell during mouse development. J Cell Biol 123:223-235, 1993.
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Zhuang Z, Park WS, Pack S, et al: Trisomy 7-harbouring nonrandom duplication of the mutatnt MET allele in hereditary papillary renal carcinomas. Nat Genet 20:66-69, 1998.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 187
EP 191
PG 5
ER
PT J
AU Chetty, R
Simelane, S
AF Chetty, Runjan
Simelane, Sobusiso
TI p53 and Cyclin A Protein Expression in Squamous Carcinoma of the Oesophagus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE oesophagus; squamous carcinoma; cell cycle; p53; cyclin A
ID oesophagus; squamous carcinoma; cell cycle; p53; cyclin A
AB The aim of this study was to explore the relationship between p53 and cyclin A immunostaining in squamous carcinomas of the oesophagus. It has been shown that both these proteins are overexpressed in poorly differentiated endometrial carcinomas. Fifty oesophagectomy specimens were analysed for p53 and cyclin A immunoexpression. This was correlated with patient age and gender and tumor stage and grade. Forty-two percent of cases were p53 positive, while 94% of the squamous cancers expressed cyclin A protein. Neither protein showed any statistically significant correlation with clinicopathological parameters. This study has demonstrated that only 42% of oesophageal squamous carcinomas from South Africa express p53 protein, while the vast majority (94%) express cyclin A protein. Neither of these proteins showed any relationship to each other or any clinical feature or the tumor grade or stage.
C1 [Chetty, Runjan] University of Natal Medical School, Private Bag 7, 4013 Durban, Congella, South Africa.
[Simelane, Sobusiso] University of Natal Medical School, Private Bag 7, 4013 Durban, Congella, South Africa.
RP Chetty, R (reprint author), University of Natal Medical School, 4013 Durban, South Africa.
EM chettyr@med.und.ac.za
CR Stemmermann G, Heffelfinger SC, Noffsinger A, et al: The molecular biology of esophageal and gastric cancer and their precursors: oncogenes, tumor suppressor genes, and growth factors. Hum Pathol 25:968-981, 1994.
Motokura T, Arnold A: Cyclins and oncogenesis. Biochima et Biphysica Acta 1155:63-78, 1993.
Shiozawa T, Xin L, Nikaido T, et al: Immunohistochemical detection of cyclin A with reference to p53 expression in endometrial endometrioid carcinomas. Int J Gynecol Pathol 16:348-353, 1997.
Hollstein MA, Metcalf RA, Welsh JA, et al: Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci USA 87:9958-9961, 1990.
Meltzer SJ, Yin J, Huang Y, et al: Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc Natl Acad Sci USA 88:4976-4980, 1991.
Uchino S, Saito T, Inomata M, et al: Prognostic significance of the p53 mutation in esophageal cancer. Jpn J Clin Oncol 26:287-292, 1996.
Wang DY, Xiang YY, Tanaka M, et al: High prevalence of p53 protein expression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis. Cancer 74:3089-3096, 1994.
Sarbia M, Porschen R, Borchard F, et al: p53 protein expression and prognosis in squamous cell carcinoma of the esophagus. Cancer 74:2218-2223, 1994.
Shimaya K, Shiozaki H, Inoue M, et al: Significance of p53 expression as a prognostic factor in oesophageal squamous cell carcinoma. Virchows Archiv Pathol Anat Histopathology 422:271-276, 1993.
Chetty R, Chetty S: Cyclin D1 and retinoblastoma protein expression in oesophageal squamous carcinoma. J Clin Pathol: Mol Pathol 50:257-260, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 193
EP 196
PG 4
ER
PT J
AU Croce, VM
Colussi, GA
Price, RM
Segal-Eiras, A
AF Croce, Virginia Maria
Colussi, Gladys Andrea
Price, R Mike
Segal-Eiras, Amada
TI Identification and Characterization of Different Subpopulations in a Human Lung Adenocarcinoma Cell Line (A549)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE A549; lung adenocarcinoma; cell subpopulations
ID A549; lung adenocarcinoma; cell subpopulations
AB The morphology, cell growth, antigenic expression and tumorigenicity of cell subpopulations from the A549 lung adenocarcinoma isolated by Percoll gradient separation have been analysed. Four subpopulations were obtained (subpopulations A, B, C and D). Immunocytochemical analysis of several antigens was performed with monoclonal antibodies (MAbs): MUC1 mucin (C595, HMFG1 and HMFG2), MUC5B (PANH2); gp230 (PANH4); carbohydrate antigens including sialyl Lewis x (KM93), Tn antigen (83D4), Lewis y (C14); 5, 6, 8, 17 and 19 cytokeratins and p53. The cell population D tended to form cell aggregates that piled up on the monolayer similar to overgrowth cultures of the A549 parental cell line, whereas A, B and C cell subpopulations formed well spread monolayers. Both parental A549 and subpopulation D secreted abundant mucus. The topographic distribution and secretion production were correlated with tumorigenic assays since only subpopulation D grew in nude mice exhibiting reduced latency period; these characteristics correlated with the fast growth of the subpopulation D in vitro. Immunocytochemical analysis demonstrated that subpopulation D showed greater expression of MUC1 mucin and carbohydrate antigens such as Tn antigen, sialyl Lewis x and Lewis y and less expression of cytokeratins, p53, MUC5B and gp230; conversely, subpopulations A, B and C showed the opposite antigenic profile. Our results illustrate heterogeneity in the A549 cell line; subpopulations A, B and C retained characteristics of more differentiated adenocarcinoma while subpopulation D displayed features of a less differentiated tumor line.
C1 [Croce, Virginia Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Colussi, Gladys Andrea] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Price, R Mike] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research LaboratoriesNottingham, UK.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM as-eiras@netverk.com.ar
CR Abe K, Hakomori S, Ohshiba S: Differential expression of difucosyl type 2 chain, Le y, defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps and adenocarcinomas. Cancer Res 46:2636-2644, 1986.
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Young LR, Wang Y, Voynow J: Neutrophil elastase up-regulates MUC5AC gene expression, 4th International Workshop on Carcinoma- Associated Mucins, Cambridge, UK., 1996.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 197
EP 204
PG 8
ER
PT J
AU Paraskevakou, H
Saetta, A
Skandalis, K
Tseleni, S
Athanassiadis, A
Davaris, SP
AF Paraskevakou, Helen
Saetta, Angelica
Skandalis, Kostas
Tseleni, Sofia
Athanassiadis, Aristides
Davaris, S Panayotis
TI Morphological-Histochemical Study of Intestinal Carcinoids and K-ras Mutation Analysis in Appendiceal Carcinoids
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE carcinoids; morphology; histogenesis; p53 mutations; ras oncogenes
ID carcinoids; morphology; histogenesis; p53 mutations; ras oncogenes
AB Intestinal carcinoids are potentially malignant neoplasms. Their histogenesis and pathogenesis are currently uncertain. The morphological and histochemical characteristics of twenty intestinal carcinoids are studied. The primary sites of three mucin-producing tumors were examined by electron microscope. Furthermore 11 appendiceal carcinoids were analysed by the polymerase chain reaction (PCR) for the detection of ras and p53 point mutations. Microscopically all carcinoids were of mixed type. Focal mucin production was evident in three carcinoids that metastasised to regional lymph nodes. HID-Alcian blue staining proved that mucin in both primary and secondary foci did not belong to the sulphated group. The secretory granules and mucin droplets found in a single neoplastic cell suggest that carcinoids of the small intestine and some of the appendix arise from the endoderm. Neither ras nor p53 mutations were detected. It seems that ras oncogenes are probably not involved in the pathogenesis of appendiceal carcinoids.
C1 [Paraskevakou, Helen] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
[Saetta, Angelica] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
[Skandalis, Kostas] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
[Tseleni, Sofia] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
[Athanassiadis, Aristides] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
[Davaris, S Panayotis] University of Athens, Department of Pathology, Medical School, 29 Deliyianni Str., GR-145 62 Kifissia, Greece.
RP Paraskevakou, H (reprint author), University of Athens, Department of Pathology, Medical School, GR-145 62 Kifissia, Greece.
EM asaettae@cc.uoa.gr
CR Ackerman’s: Surgical Pathology, ed. Rosai J, The CV Mosby Company, 8th edition, 1995.
Alpert S, Hanahan D, Teitelman G: Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53:295-308, 1998.
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Anderson N, Somerville J, Johnston C, et al: Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study. Histopathology 18:61-65, 1991.
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Aubock L, Ratzenhofer M: Extraepithelial enterochromaffin cell-herve-fibre. Complexes in the normal human appendix and in neurogenic appendicopathy. J Pathol 136:217-226, 1982.
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Laurent-Puig P, Olschwang S, Delattre O Validere: Association of Ki-ras mutation with differentiation and tumor-formation pathways in colorectal carcinoma. Int J Cancer 49:220-223, 1991.
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Lohmann DR, Fesseler B, Putz B: Infrequent mutations of p53 gene in pulmonary carcinoid tumors. Cancer Res 53:5797- 5801, 1993.
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Moyana T, Satkunam N: A comparative immunohistochemical study of jejunoileal and appendiceal carcinoids. Implications for histogenesis and pathogenesis. Cancer 70:1081-1088, 1992.
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O’Dowd G, Gosney JR: Absence of overexpression of p53 protein by intestinal carcinoid tumors. J Pathol 175:403-404, 1995.
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Raju G, Lee Y: Gastrointestinal carcinoid tumors: Histological, histochemical and immunohistochemical study. Ann Acad Med Singapore 17:81-88, 1988.
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Shaw P: The topografical and age distribution of neuroendocrine cells in normal human appendix. J Pathol 164:235-239, 1991.
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Soga J, Tazawa K: Pathologic analysis of carcinoids. Histologic reevaluation of 62 cases. Cancer 28:990-998, 1971.
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Younes N, Fulton N, Tanaka R, et al: The presence of K-12 ras mutations in duodenal adenocarcinomas and the absence of ras mutations in other small bowel adenocarcinomas and carcinoid tumors. Cancer 79:1804-1808, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 205
EP 210
PG 6
ER
PT J
AU Gunawan, B
Granzen, B
Keller, U
Steinau, G
Fuzesi, L
Schumpelick, V
Mertens, R
AF Gunawan, Bastian
Granzen, Bernd
Keller, Uma
Steinau, Gerd
Fuzesi, Laszlo
Schumpelick, Volker
Mertens, Rolf
TI Clinical Aspects of Alveolar Rhabdomyosarcoma with Translocation t(1;13)(p36;q14) and Hypotetraploidy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE alveolar rhabdomyosarcoma; soft tissue; cytogenetics; chromosome
ID alveolar rhabdomyosarcoma; soft tissue; cytogenetics; chromosome
AB Although most cases of alveolar rhabdomyosarcoma (RMS) are characterized by the chromosomal translocation t(2;13)(q35;q14), several cases have been reported with a variant t(1;13)(p36;q14). We present the clinical, morphological and cytogenetic features of an alveolar RMS in a 4-year-old boy. Chromosomal analysis revealed a hypertriploid to hypotetraploid karyotype with a t(1;13)(p36;q14) in all tumor cells. It appears that alveolar RMS with t(1;13) occurs in younger children and displays a higher incidence to upper and lower extremity than tumors with t(2;13).
C1 [Gunawan, Bastian] Georg-August-University, Department of PathologyGottingen, Germany.
[Granzen, Bernd] Medical Faculty of the Technical University, Department of Pediatrics, RWTH, Pauwelsstr. 30, D-52057 Aachen, Germany.
[Keller, Uma] Medical Faculty of the Technical University, Department of Pediatrics, RWTH, Pauwelsstr. 30, D-52057 Aachen, Germany.
[Steinau, Gerd] Medical Faculty of the Technical University, Department of SurgeryAachen, Germany.
[Fuzesi, Laszlo] Georg-August-University, Department of PathologyGottingen, Germany.
[Schumpelick, Volker] Medical Faculty of the Technical University, Department of SurgeryAachen, Germany.
[Mertens, Rolf] Medical Faculty of the Technical University, Department of Pediatrics, RWTH, Pauwelsstr. 30, D-52057 Aachen, Germany.
RP Mertens, R (reprint author), Medical Faculty of the Technical University, Department of Pediatrics, D-52057 Aachen, Germany.
CR Anderson J, Renshaw J, McManus A, et al: Amplification of the t(2;13, and t(1;13, translocations of alveolar rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse transcriptase polymerase chain reaction. Am J Pathol 150:477- 482, 1997.
Biegel JA, Meek RS, Parmiter AH, et al: Chromosomal translocation t(1;13)(p36;q14, in a case of rhabdomyosarcoma. Genes Chromosomes Cancer 3:483-484, 1991.
Dal Cin P, Brock P, Aly MS, et al: A variant, 2;13, translocation in rhabdomyosarcoma. Cancer Genet Cytogenet 55:191-195, 1991.
Davis RJ, D’Cruz CM, Lovell MA, et al: Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14, translocation in alveolar rhabdomyosarcoma. Cancer Res 54:2869-2872, 1994.
De Zen L, Sommaggio A, d’Amore ESG, et al: Clinical relevance of DNA ploidy and proliferative activity in childhood rhabdomyosarcoma: A retrospective analysis of patients enrolled onto the Italien Cooperative Rhabdomyosarcoma Study RMS88. J Clin Oncol 15:1198-1205, 1997.
Douglass EC, Rowe ST, Valentine M, et al: Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma. Genes Chromosom Cancer 3:480-482, 1991.
Douglass EC, Valentine M, Etcubanas E, et al: A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet 45:148-155, 1987.
Douglass EC, Shapiro DN, Valentine M, et al: Alveolar Rhabdomyosarcoma with the t(2;13): cytogenetic findings and clinicopathologic correlations. Med Pediatr Oncol 21:83-87, 1993.
Enzinger FM, Weiss S: Soft Tissue Tumors. Third edition. St. Louis: Mosby-Year Book, Inc., 1995.
ISCN, 1995): An International System for Human Cytogenetic Nomenclature, Mitelman F, ed). S. Karger, Basel, 1995.
Kelly KM, Womer RB, Sorensen PHB, et al: Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol 15:1831-1836, 1997.
Klingebiel T, Pertl U, Hess CF, et al: Treatment of children with relapsed soft tissue sarcoma: report of the german CESS/CWS REZ 91 trial. Med Pediatr Oncol 30:269-275, 1998.
Multizentrische Therapiestudie zur Behandlung von Kindern und Jugendlichen mit Weichteilsarkomen, Cooperative Weichteilsarkomstudie CWS-91, Fassung vom 10. Mai 1991.
Newton WA Jr, Gehan EA, Webber BL, et al: Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification – an Intergroup Rhabdomyosarcoma Study Cancer 76:1073-1085, 1995.
Shapiro DN, Parham DM, Douglass EC, et al: Relationship of tumor cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma. J Clin Oncol 9:159-166, 1991.
Shapiro DN, Sublett JE, Baitao LI, et al: Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res, 53:5108-5112, 1993.
Turc-Carel C, Lizard-Nacol S, Justrabo E, et al: Consistent chromosomal translocation in alveolar rhabdomyosarcoma. Cancer Genet Cytogenet 19:361-362, 1986.
Wang-Wuu S, Soukup S, Ballard E, et al: Chromosomal analysis of sixteen human rhabdomyosarcomas. Cancer Res 48:983- 987, 1988.
Whang-Peng J, Knutsen T, Theil K, et al: Cytogenetic studies in subgroups of rhabdomyosarcoma. Genes Chromosom Cancer 5: 299-310, 1992.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 211
EP 213
PG 3
ER
PT J
AU Du, B
Wang, P
Guo, X
Du, B
AF Du, Bo
Wang, Ping
Guo, Xiaofeng
Du, Baodong
TI Expression of Membrane type 1-Matrix Metalloproteinase in Laryngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE laryngeal carcinoma; MT1-MMP; invasion; metastasis
ID laryngeal carcinoma; MT1-MMP; invasion; metastasis
AB Membrane type 1-matrix metalloproteinase (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components of the extracellular matrix and activates progelatinase A (MMP-2) at the cell surface. In this study, we analyzed the expression of MT1-MMP mRNA in 45 cases of laryngeal carcinoma by RT-PCR and investigated the relationship between MT1-MMP expression and survival in 18 cases. The result showed that the expression of MT1-MMP mRNA was higher in tumor tissue than in corresponding normal tissue. The tumoral expression in clinical stage III was higher than in stage II. The tumoral expression level of MT1-MMP mRNA in patients with lymph node metastasis was signigicantly higher than those with negative lymph nodes. The patients with high expression level showed significantly poorer 5 year survival than those with low expression level. Collectively, our findings suggest that the high level of MT1-MMP expression is closely related to the invasion and metastasis of laryngeal carcinoma, and indicates poorer prognosis.
C1 [Du, Bo] Norman Bethune University of Medical Sciences, Department of ENT & HN, First Clinical Hospital, 130021 Changchun, China.
[Wang, Ping] Norman Bethune University of Medical Sciences, Department of ENT & HN, First Clinical Hospital, 130021 Changchun, China.
[Guo, Xiaofeng] Norman Bethune University of Medical Sciences, Department of ENT & HN, First Clinical Hospital, 130021 Changchun, China.
[Du, Baodong] Norman Bethune University of Medical Sciences, Department of ENT & HN, First Clinical Hospital, 130021 Changchun, China.
RP Du, B (reprint author), Norman Bethune University of Medical Sciences, Department of ENT & HN, First Clinical Hospital, 130021 Changchun, China.
EM dubo2000@hotmail.com
CR Matrisian LM: Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121-125, 1990.
Woessner JFJ: Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145-2154, 1991.
Cao J, Sato H, Takino T, et al: The C-terminal region of membrane type matrix metalloproteinase is a functional transmembrane domain required of pro-gelatinase A activation. J Biol Chem 270:801-805, 1995.
Emonard HP, Remacle AG, Noel AC, et al: Tumor cell surfaceassociated binding site for the Mr 72.000 type IV collagenase. Cancer Res 52:5845-5848, 1992.
Pei D, Weiss S: Transmembrane-deletion mutants of the membrane- type matrix metalloproteinase-1 process proglatianse A and express intrinsic matrix-degrading activity. J Biol Chem 271:9135-9140, 1996.
Kinoshita T, Sato H, Takino T, et al: Processing of a precursor of 72kDa type IV collagenase/gelatinase A by a recombinant membrane type 1 matrix metalloproteinase. Cancer Res 56:2535-2538, 1996.
Sato H, Takino T, Okada Y, et al: A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370:61-65, 1994.
Bando E, Yonemura Y, Endou Y, et al: Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis. Oncol Rep 5: 1483-1488, 1998.
Mori M, Mimori K, Shiraishi T, et al: Analysis of MT1-MMP and MMP2 expression in human gastric cancers. Int J Cancer 74:316-321, 1997.
Yamamoto M, Mahanam S, Sawaya R, et al: Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro. Cancer Res 56:384-392, 1996.
Gilles C, Polette M, Piette J, et al: High level of MT1-MMP expression is associated with invasiveness of cervical cancer cells. Int J Cancer 65:209-213, 1996.
Tokuraku M, Sato H, Shinagawa A, et al: Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinoma correlation with the expression of membranetype matrix metalloproteinase 1, MT1-MMP, and with lymph node metastasis. Int J Cancer 64: 355-359, 1995.
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Repassy G, Forster-Horvath Cs, Juhasz A, et al. Expression of invasion markers CD44v6/v3, nm23 and MMP2 in laryngeal and hypopharyngeal carcinoma. Pathol Oncol Res 4:14-22, 1998.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 214
EP 217
PG 4
ER
PT J
AU Banfalvi, T
Gilde, K
Boldizsar, M
Kremmer, T
Otto, Sz
AF Banfalvi, Teodora
Gilde, Katalin
Boldizsar, Mariann
Kremmer, Tibor
Otto, Szabolcs
TI Serum levels of S-100 protein and 5-S-cysteinyldopa as markers of melanoma progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE melanoma; S-100 protein; 5-S-cysteinyldopa
ID melanoma; S-100 protein; 5-S-cysteinyldopa
AB Serum S-100 protein is widely used as a marker of melanoma and since 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin its serum and urinary levels can reflect melanoma progression. In this study we examined the concentration changes of serum S-100 protein and 5-S-CD in 252 melanoma patients of different clinical stages. Serum samples were taken from 252 melanoma patients at 860 times, from June 1996 to July 1998. The serum S-100 protein was measured by the immunoluminometric assay, levels of 5-S-CD was determined by HPLC. The value of S-100 protein in patients with primary melanoma (0.11m mg/l) and in patients without symptoms (0.15 m mg/l) ranged around the normal level (0.01–0.12 m mg/l). There was a significant difference between the values of patients with or without symptoms. There was a similarly significant difference between the S-100 values of clinical Stage I (0.11 mg/l) and Stage III (2.91 mg/l) as well as between those of clinical Stage II (0.47 mg/l) and Stage III (2.91 mg/l), respectively. Analyzing the values of patients with symptoms we observed significant difference between the S-100 protein values of patients with primary tumor and those with solitary or multiple distant metastases. In case of 5-S-CD significant difference was found between clinical Stage I and III as well as clinical Stage II and III. Furthermore, there was a significant difference between the mean marker values of patients with primary tumor, lymph node, lung metastasis and clinical stage III.
C1 [Banfalvi, Teodora] National Institute of Oncology, Department of Dermatology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Department of Dermatology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Boldizsar, Mariann] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Kremmer, Tibor] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Otto, Szabolcs] National Institute of Oncology, Central Clinical Laboratory, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Banfalvi, T (reprint author), National Institute of Oncology, Department of Dermatology, H-1122 Budapest, Hungary.
EM banfalvi@oncol.hu
CR Agrup G, Agrup P, Andersson T, et al: 5 years experience of 5- S-cysteinyldopa in melanoma diagnosis. Acta Dermatovener, Stockholm, 59:381-388, 1979.
Benathan M: Modulation of 5-S-cysteinyldopa formation by tyrosinase activity and intracellular thiols in human melanoma cells. Melanoma Res 6:183-189, 1996.
Bonfrer JM, Korse CM, Israels SP: Serum S-100 has prognostic significance in malignant melanoma. Anticancer Res 17:2975-7, 1997.
Buer J, Probst M, Franzke A, et al: Elevated serum levels of S- 100 and survival in metastatic malignant melanoma. Br J Cancer 75:1373-6, 1997.
Cho K, Hashimoto K, Taniguchi Y, et al: Immunohistochemical study of melanocytic nevus and malignant melanoma with monoclonal antibodies against S-100 subunit. Cancer 66:765- 771, 1990.
Fagnart CO, Sindic MJ, Laterre CH: Particle counting immunassay of S-100 protein in serum. Possible relevance in tumours and ischemic disorders of the central nervous system. Clin Chem 34:1387-1391, 1988.
Gaynor R, Irie R, Morton D: S-100 protein is present in cultured human malignant melanomas. Nature 286:400-401, 1980.
Gaynor R, Irie R, Morton D, et al: S-100 protein: A marker for human malignant melanoma? Lancet 18:869-871, 1981.
Guo HB, Stoffel-Wagner B, Bierwirth T, et al: Clinical significance of serum S-100 in metastatic malignant melanoma. Eur J Cancer 31:1898-1902, 1995.
Hanson LO, Schoultz E, Djuren E, et al: Prognostic value of serum analyses of S-100 protein beta in malignant melanoma. Anticancer Res 17:3071-3073, 1997.
Hasegawa M, Takata M, Hatta N, et al: Simultaneous measurement of serum 5-S-cysteinyldopa, circulating intercellular adhesion molecule-1 and soluble interleukin-2 receptor levels in Japanese patients with malignant melanoma Melanoma Res 7:243-251, 1997.
Henze G, Dummer R, Joller-Jemelka H, et al: Serum S-100 – a marker for disease monitoring in metastatic melanoma. Dermatology 194:208-212, 1997.
Hirai S, Kageshita T, Kimura T, et al: Serum levels of s-ICAM, and 5-S-cysteinyldopa as markers of melanoma progression. Melanoma Res 7:58-62, 1997.
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Ketcham AS, Moffat FL, Balch CM: Classification and staging In: CM Balch Cutaneous melanoma Philadelphia, JB Lippincott, 1992, pp. 213-220.
Meyerhoffer S, Lindberg Z, Hager A, et al: Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in children Acta Derm Venereol 78:31-35, 1998.
Miliotes G, Lyman GH, Cruse CW, et al: Evalutaiton of new putative tumor markers for melanoma Ann Surg Oncol 3:558-563, 1996.
Nakajima T, Watanabe S, Sato Y, et al: Immunohistochemical demonstration of S-100 protein in malignant melanoma and pigmented nevus and its diagnostic application. Cancer 50:912- 918, 1982.
Nyberg L, Kroon L, Ullen A, et al: Sangtec LIA a new sensitive monoclonal assay for measuring protein S 100 in patients with malignant melanoma in Final Program and Abstract Book of the XXIV Meeting of ISOBM. San Diego, 1996.
Peterson L, Woodward W, Fletcher W, et al: Plasma 5-S-cysteinyldopa differentietes patients with primary and metastatic melanoma from patients with dysplasticus naevus syndroma and normal subjects. J Am Acad Dermatol 19:509-515, 1988.
Schoultz E, Hansson LO, Djureen E, et al: Prognostic value of serum analyses of S-100 beta protein in malignant melanoma. Melanoma Res 6:133-137, 1996.
Schoultz ES, Diepgen TL, Von Den Driesch P: Clinical and prognostic relevance of serum S-100 beta protein in malignant melanoma Br J Dermatol 138:426-430, 1998.
Sasaki Y, Shimizu H, Naka W, et al: Evaluation of the clinical usefulness of measuring urinary excretion of 5-S-cysteinyldopa in melanoma: ten years experience of 50 patients Acta Derm Venerol 77:379-381, 1998.
Wakamatsu K, Ito S: Seasonal variations in serum concentration of 5-S- cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxyl acid in healthy Japanese. Pigment Cell Res 8:132-134, 1995.
Wimmer I, Meyer CJ, Seifert B, et al.: Prognostic value of serum 5-S-cysteinyldopa for monitoring human metastatic melanoma during immunochemoterapy. Cancer Res 57:5073-5076, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 218
EP 222
PG 5
ER
PT J
AU Durmaz, R
Deliorman, S
Isiksoy, S
Uyar, R
Erol, K
Tel, E
AF Durmaz, Ramazan
Deliorman, Selda
Isiksoy, Serap
Uyar, Ruhi
Erol, Kevser
Tel, Esref
TI Antiproliferative Properties of the Lazaroids U-83836E and U-74389G on Glioma Cells In Vitro
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glioma; C6; MTT; 21-aminosteroids; U-83836E; U-74389G
ID glioma; C6; MTT; 21-aminosteroids; U-83836E; U-74389G
AB The 21-aminosteroids (lazaroids) are a new family of steroid compounds that inhibit lipid peroxidation reactions. They are novel antioxidant agents, which have been shown to have antiproliferative properties on cancer cells and also are thought to prevent free radical-mediated blood-brain barrier damage. In order to understand the effect of lazaroids on glioma, we tested U-83836E and U-74389G at doses ranging between 0.1–100 m mM on primary cultures of glioblastoma multiforme from three patients, rat C6 glioma cell line, and 5 th subculture established from one of the patients. The effects of both compounds on cell proliferation were determined using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay. U-83836E in the primary cultures was found to have 50% inhibitory concentrations (IC50 ) of 6.30, 6.75 and 6.50 m mM, respectively. The IC50 value of U-74389G was calculated as 91 m mM in only one of the patients. On C6 glioma cells, while the IC50 of U-83836E was 45 m mM, U-74389G showed no cytotoxic effect. On the 5 th subculture, U-83836E had an IC50 of 37.5 m mM, but the cytotoxic effects of U-74389G was less than in that of the primary culture. In conclusion, these compounds were found to be more cytotoxic in primary culture than the cell lines and there were also differences between their members in the inhibition of cell survival.
C1 [Durmaz, Ramazan] Medical Faculty of Osmangazi University, Department of Neurosurgery, 90-26480 Eskisehir, Turkey.
[Deliorman, Selda] Medical Faculty of Osmangazi University, Department of PhysiologyEskisehir, Turkey.
[Isiksoy, Serap] Eskisehir Osmangazi University, Faculty of Medicine, Department of PathologyEskisehir, Turkey.
[Uyar, Ruhi] Medical Faculty of Osmangazi University, Department of PhysiologyEskisehir, Turkey.
[Erol, Kevser] Medical Faculty of Osmangazi University, Department of PharmacologyEskisehir, Turkey.
[Tel, Esref] Medical Faculty of Osmangazi University, Department of Neurosurgery, 90-26480 Eskisehir, Turkey.
RP Durmaz, R (reprint author), Medical Faculty of Osmangazi University, Department of Neurosurgery, 90-26480 Eskisehir, Turkey.
EM rdurmaz@ogu.edu.tr
CR Alley MC, Scudiero DA, Monks A, et al: Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48:589-601, 1988.
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Braughler JM, Hall ED, Jacobson EJ, et al: The 21-aminostroids: Potent inhibitors of lipid peroxidation for the treatment of central nervous system trauma and ischemia. Drugs of Future 14:143-152, 1989.
Buatti JM, Friedman WA, Theele DP, et al. The lazaroid U- 74389G protects normal brain from stereotactic radiosurgeryinduced radiation injury. Int J Radiation Oncology Biol Phys 34:591-597, 1996.
Carmichael J, DeGraff WG, Gazdar AF, et al: Evaluation of tetrazolium- based semiautomated colorimetric assay: assesment of chemosensitivity testing. Cancer Res 47:936-942, 1987.
Chen TT, Mealey J: Microculture of human brain tumors. Cancer Chemother Rep 54: 9-14, 1970.
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Freshney RI: Effects of glucocorticoids on glioma cells in culture. Minireview on cancer research. Exp Cell Biol 52:286-292, 1984.
Giese H, Mertsch K, Blasig IE: Effect of MK-801 and U83836E on a porcine brain capillary endothelial cell barrier during hypoxia. Neuroscience Letters 191:169-172, 1995.
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Hall ED, Andrus PK, Smith SL, et al: Neuroprotective efficacy of microvasculary-localized versus brain-penetrating antioxidants. Acta Neurochir, suppl, 66:107-113, 1996.
Hall ED, Braughler JM, Yonkers PA, et al: U-78517F: A potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia. J Pharmacol Exp Ther 258:688-694, 1991.
Hall ED, Yonkers PA, McCall JM, et al: Effects of the 21- aminosteroid U74006F on experimental head injury in mice. J Neurosurg 68:456-461, 1988.
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Muller TB, Haraldseth O, Jones RA, et al: Perfusion and diffusion- weighted MR imaging for in vitro evaluation of treatment with U-74389G in rat stroke model. Stroke 26:1453-1458, 1995.
Pertuiset B, Dougherty D, Cromeyer C, et al: Stem cell studies of human malignant brain tumors. Part 2: proliferation kinetics of brain-tumor cells in vitro in early-passage cultures. J Neurosurg 63:426-432, 1985.
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Smith SL, Scherch HM, Hall ED: Protective effect of tirilazad mesylate and metabolite U-89678 against blood-brain barrier damage after subarachnoid hemorrrage and lipid peroxidative neuronal injury. J Neurosurg 84:229-233, 1996.
Thomas DGT, Darling JL, Paul EA, et al: Assay of anticancer drugs tissue culture: relationship of relapse free interval, RFI, and in vitro chemosensitivity in patients with malignant cerebral glioma. Br J Cancer 51:525-532, 1985.
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Vincent AJPE, Esandi MC, Avezaat CJJ, et al: Preclinical testing of recombinant adenoviral herpes simplex virus-thymidine kinase gene therapy for central nervous system malignancies. Neurosurgery 41:442-452, 1997.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 223
EP 228
PG 6
ER
PT J
AU Ustun, C
Ozcan, M
Gurman, G
Cakir, M
Erekul, S
Akyol, G
Arat, M
Celebi, H
Idlman, R
Ilhan, O
Demirer, T
Beksac, M
Koc, H
AF Ustun, Celalettin
Ozcan, Muhit
Gurman, Gunhan
Cakir, Mehtap
Erekul, Selim
Akyol, Gulen
Arat, Mutlu
Celebi, Harika
Idlman, Ramazan
Ilhan, Osman
Demirer, Taner
Beksac, Meral
Koc, Haluk
TI Differences in Liver Pathology and Clinical Outcome Between Two Patients with Hepatitis B Virus and Graft Versus Host Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE alloBMT; hepatitis B virus; graft versus-host disease
ID alloBMT; hepatitis B virus; graft versus-host disease
AB Our two patients undergoing allogeneic bone marrow transplantation (AlloBMT) had both Hepatitis B virus (HBV) and graft-versus-host disease (GVHD). In the first patient, liver enzymes elevated three months after AlloBMT, and GVHD was diagnosed. Two weeks after the diagnosis of GVHD, HBsAg appeared in his serum. At that time, liver biopsy was not able to discriminate two disorders, but his sequential liver biopsies disclosed GVHD. Despite the patient was treated with cyclosporin A (CsA), he died for chronic GVHD. In contrast to the first patient, the second patient had HBsAg prior to GVHD. His liver enzymes deterioration was detected in the first month after AlloBMT, and reached the highest level in the third month while withdrawing CsA. In the fifth month he developed scleradermatous skin changes, and skin biopsy revealed chronic GVHD, whereas concurrent liver biopsy revealed chronic active hepatitis. This observation showed that immunosuppressive conditions such as GVHD or its prophylaxis may affect the appearance of liver pathology caused by HBV, which depends on the time of GVHD development, and the duration and depth of GVHD prophylaxis.
C1 [Ustun, Celalettin] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Ozcan, Muhit] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Gurman, Gunhan] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Cakir, Mehtap] Ankara University, School of Medicine, Department of PathologyAnkara, Turkey.
[Erekul, Selim] Ankara University, School of Medicine, Department of PathologyAnkara, Turkey.
[Akyol, Gulen] Gazi University, School of Medicine, Department of PathologyGazi, Turkey.
[Arat, Mutlu] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Celebi, Harika] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Idlman, Ramazan] Ankara University, School of Medicine, Department of GastroenterologyAnkara, Turkey.
[Ilhan, Osman] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Demirer, Taner] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Beksac, Meral] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
[Koc, Haluk] Ankara University, School of Medicine, Department of Hematology, Ibni Sina Hospital, 06100 Ankara, Sihhiye, Turkey.
RP Koc, H (reprint author), Ankara University, School of Medicine, Department of Hematology, 06100 Ankara, Turkey.
EM ustun@pallas.dialup.ankara.edu.tr
CR Atkinson K: Recostruction of the haemopoietic and immune systems after marrow transplantation. Bone Marrow Transplant 5:209-226, 1990.
Chen PM, Fan S, Liu JH, et al: Reactivation of hepatitis B virus in two chronic GVHD patients after transplant. Int J Hematol 58:183-188, 1993.
Chen PM, Fan S, Liu CJ, et al: Changing of hepatitis B virus markers in patients with bone marrow transplantation. Transplantation 49:708-713, 1990.
Gerber MA, Thung SN: Biology of disease molecular and cellular pathology of hepatitis B.Lab Invest 53:572-590, 1985.
Hoofnagle JH, Dusheiko GM, Schafer DF, et al: Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Int Med 96:447-449, 1982.
Lau GKK, Liang R, Chiu EKW, et al: Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study. Bone Marrow Transplant 19:795-799, 1997.
Lawrence GL: Immune recovery after bone marrow transplantation. Hematol/Oncol Clin N Am 4:659-675, 1990.
Locasciulli A, Alberti A, Bock R, et al. Impact of liver disease and hepatitis infections on allogeneic bone marrow transplantation in Europe: a survey from the European Bone Marrow Transplantation, EBMT, Groupe – Infections Diseases Working Party. Bone Marrow Transplant 14:833-837, 1994.
Locasciulli A, Bacigalupo A, Vanlint MT, et al: Hepatitis B virus infection and liver disease after allogeneic bone marrow transplantation. A report of 30 cases. Bone Marrow Transplant 6:25- 29, 1990.
Pariente EA, Goudeau, Dubois F, et al: Fulminant hepatitis due to reactivation of chronic hepatitis B virus infection after allogeneic bone marrow transplantation. Dig Dis Sci 33:1185- 1191, 1988.
Ustun C, Koc H, Karayalcyn S, et al: Hepatitis B virus infection in allogeneic bone marrow transplantation. Bone Marrow Transplant 20:289-296, 1997.
Ustun C, Idilman R, Gurman G, et al. Hematopoietic stem cell transplantation in patients with non-replicative hepatitis B virus carriers is safe. J Hepatol, in press).
Webster A, Brenner MK, Prentice HG, et al: Fatal hepatitis B reactivation after autologous bone marrow transplantation. Bone Marrow Transplant 49:708-713, 1989.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 229
EP 232
PG 4
ER
PT J
AU Strausz, J
Soltesz, I
AF Strausz, Janos
Soltesz, Ibolya
TI Bronchial Capillary Hemangioma in Adults
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE hemangioma; bronchus; hemoptysis
ID hemangioma; bronchus; hemoptysis
AB Two cases with capillary hemangioma of the trachea and the left upper lobe bronchus are presented. The adult patients were referred to the hospital because of hemoptysis and cough. The chest radiographs were normal in both cases. The bronchoscopic examination revealed circumscribed lesions with a capillarized surface protruding into the lumen of the trachea and the left upper lobe bronchus, respectively. The lesions were excised in toto with flexible bronchoscopic forceps. The specimens contained typical capillary hemangiomas without any signs of malignancy. Capillary hemangioma in the bronchial tree is an extremely rare benign lesion in adults. Nevertheless, it should be considered as a possible cause of hemoptysis and cough.
C1 [Strausz, Janos] National Koranyi Institute of Pulmonology, Piheno u. l., H-1529 Budapest, Hungary.
[Soltesz, Ibolya] National Koranyi Institute of Pulmonology, Piheno u. l., H-1529 Budapest, Hungary.
RP Strausz, J (reprint author), National Koranyi Institute of Pulmonology, H-1529 Budapest, Hungary.
EM str12196@helka.iif.hu
CR Dail DH: Uncommon Tumors. ln: Dail DH, Hammar SP, Eds. Pulmonary Pathology. Springer-Verlag, New York, 847-972, 1988.
Franks R, Rothera M: Cardiopulmonary bypass for resection of low tracheal haemangioma. Arch Dis Child 65:630-632, 1990.
Harding IR, Williams J, Seal RM: Pedunculated capillary haemangioma of the bronchus. Br J Dis Chest 72:336-342, 1978.
Mori S: Sclerosing hemangioma of the lung. Dis Chest 54:71-74, 1968.
Paul KP, Borner C, Muller KM, et al: Capillary hemangioma of the right main bronchus treated by sleeve resection in infancy. Am Rev Respir Dis 143:876-879, 1991.
Prakash UBS, Freitag L: Hemoptysis and Bronchoscopy-Induced Hemorrhage. In: Prakash UBS, Ed. Bronchoscopy. Raven Press New York. 227-251, 1994.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 233
EP 234
PG 2
ER
PT J
AU Chuang, ShS
Lin, ChN
Chu, ChH
Chen, FF
AF Chuang, Shih-Sung
Lin, Ching-Nan
Chu, Chien-Hui
Chen, Fen-Fen
TI Small Cell Carcinoma of the Gallbladder: Report of Two Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE gallbladder; small cell carcinoma; endocrine cell carcinoma; neuroendocrine carcinoma
ID gallbladder; small cell carcinoma; endocrine cell carcinoma; neuroendocrine carcinoma
AB Two Taiwanese patients with gallbladder small cell carcinoma are reported. One is a 79 year-old male, the other, a 86 year-old female. They both presented with the symptom/signs of acute cholecystitis and underwent cholecystectomy. An intramural mass in the gallbladder neck region was found in the first patient, while the second patient had a transmural indurated tumor in the gallbladder body with extension to the neck region. Characteristic histological and immunohistochemical features of small cell carcinoma were present in both, and electron dense neurosecretory granules were identified in the second. To our knowledge, the second patient is the oldest ever reported. The first patient received chemotherapy directed toward the initial erroneous diagnosis of non-Hodgkin’s lymphoma and developed liver metastasis in two months. The second patient did not receive chemotherapy due to her poor general condition and local recurrence occurred in six weeks. Both passed away three and five months after surgery, respectively.
C1 [Chuang, Shih-Sung] Chi-Mei Foundation Hospital, Department of Pathology, 901, Chung Hwa Road, 710 Yung Kang City, Tainan county, Taiwan, Republic of China.
[Lin, Ching-Nan] Chi-Mei Foundation Hospital, Department of Pathology, 901, Chung Hwa Road, 710 Yung Kang City, Tainan county, Taiwan, Republic of China.
[Chu, Chien-Hui] Sin-Lau Christian Hospital, Department of SurgeryTaichung, Taiwan, Republic of China.
[Chen, Fen-Fen] National Cheng-Kung University Hospital, Department of PathologyTainan, Taiwan, Republic of China.
RP Chuang, ShS (reprint author), Chi-Mei Foundation Hospital, Department of Pathology, 710 Yung Kang City, Taiwan, Republic of China.
EM ssc6061@msl6.hinet.net
CR Tahara E: Endocrine tumors of the gastrointestinal tract: classification, function and biological behavior. Digest Dis Pathol 1:121-47, 1988.
Yamamoto M, Nakajo S, Miyoshi N, et al: Endocrine cell carcinoma, carcinoid, of the gallbladder. Am J Surg Pathol 13:292- 302, 1989.
Ron IG, Wigler N, Ilie B, et al: Small cell carcinoma of the gallbladder: clinical course and response to chemotherapy. Tumori 78:207-210, 1992.
Albores-Saavedra J, Molberg K, Henson DE: Unusual malignant epithelial tumors of the gallbladder. Semin Diagno Pathol.. 13:326-338, 1996.
Nishigami T, Yamada M, Nakasho K, et al: Carcinoid tumor of the gall bladder. Int Med 35:953-956, 1996.
Cavazzana AO, Fassina AS, Tollot M, et al: Small-cell carcinoma of the gallbladder: An immunocytochemical and ultrastructural study. Pathol Res Pract 187:472-476, 1991.
Nishihara K, Nagai E, Tsuneyoshi M, et al: Small cell carcinoma combined with adenocarcinoma of the gallbladder. Arch Pathol Lab Med. 118:177-181, 1994.
Muraina UI, Tank R, Dhingra C, et al: Small cell carcinoma of gallbladder: report of two cases. Am J Gastroenterol 91:792- 794, 1996.
Albores-Saavedra J, Cruz-Ortiz H, Alcantara-Yazques A, et al: Unusual types of gallbladder carcinoma. Arch Pathol Lab Med 105:287-293, 1981.
Cavazzana AO, Fassina AS, Tollot M, et al: Small cell carcinoma of gallbladder. An immunohistochemical and ultrastructural study. Path Res Pract 187:472-476, 1991.
Cox WF Jr., Pierce GB: The endodermal origin of the endocrine cell of an adenocarcinoma of the colon of the rat. Cancer 50: 1530-1538, 1982.
Nash SV, Said JW: Gastropancreatic neuroendocrine tumors. A histochemical and immunohistochemical study of epithelial, keratin proteins, carcinoembryonic antigen, and neuroendocrine, neuron specific enolase, bombesin and chromogranin, markers in foregut, midgut and hindgut tumors. Am J Clin Pathol 86:415- 22, 1986.
Mosnier JF, Brousse N, Sevestre C, et al: Primary low-grade Bcell lymphoma of the mucosa-associated lymphoid tissue arising in the gallbladder. Histopathology 1992; 20:273-275, 1992.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 235
EP 238
PG 4
ER
PT J
AU Mandoky, L
AF Mandoky, Laszlo
TI Amphicrine Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE amphicrine; adenocarcinoid; neuroendocrine; mucus granules; dense-core granules
ID amphicrine; adenocarcinoid; neuroendocrine; mucus granules; dense-core granules
AB The term amphicrine refers to cells, and tumors, which show both exocrine and endocrine features. Author’s aim was to analyse the characteristics of these neoplasms. 40 suspicious cases were reviewed. Mucin-stains (PAS, diastase-PAS, Stains-all, Alcian-blue), immunohistochemistry (antibodies against Neuron-Specific Enolase (NSE), and Chromogranin A (CGA), and electronmicroscopic studies were performed to demonstrate exocrine and/or endocrine features of the tumor cells. By means of these methods, 16 cases turned out to be amphicrine tumors. Among them, there were 4 sinonasal, 1 bronchial, 1 mediastinal, 8 gastrointestinal and 2 suprarenal gland neoplasms. In connection to the subject, a brief review is given of amphicrine tumor, regarding its etiological and pathological aspects. These tumors form a distinct clinicopathological entity and should be separated from both neuroendocrine tumors and adenocarcinomas.
C1 [Mandoky, Laszlo] Fovarosi Uzsoki utcai Korhaz, Pathologia, Uzsoki utca 29., H-1145 Budapest, Hungary.
RP Mandoky, L (reprint author), Fovarosi Uzsoki utcai Korhaz, Pathologia, H-1145 Budapest, Hungary.
EM mandlasz@mail.matav.hu
CR Al-Talib RK, Mason CH, and Theaker JM: Combined goblet cell carcinoid and mucinous cystadenoma of the appendix. J Clin Pathol 48:869-870, 1995.
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Azzopardi JG, and Hou LT: Intestinal metaplasia with argentaffin cell in cervical adenocarcinoma. J Pathol Bact 90:686-690, 1965.
Borch K, Renvall H, Kullman E, et al: Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases. Am J Surg Pathol 11:435- 444, 1987.
Borchard FZ: Das diffuse endokrine System und die Karzinoide des Gastro-intestinaltraktes. Gastroenterologie 20:187-205, 1982.
Bordi C, D`Addo T, Pilato FP, et al: Carcinoid, ECL cell, tumor of the oxynic mucosa of the stomach: a hormone dependent neoplasm? In: Progress in surgical pathology., Eds: Fenoglio- Preister C, Wolff M, and Rilke F, Vol 8. Philadelphia: Field & Wood, 1988, pp. 177-195.
De Bruine AP, Dinjens WNM, Zijlema JH L, et al: Renewal of enterochromaffin cells in the rat caecum. Anat Rec 233:75-82, 1992b.
De Bruine A P, Wiggers Th, Beek C et al.: Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance. Int J Cancer 54:765-771, 1993.
Capella C, Eusebi V, Mann B, et al: Endocrine differentiation in mucoid carcinoma of the breast. Hystopathol 4:613-630, 1980.
Capella C, Usellini L, Papotti M, et al.: Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Breast. Ultrastruct Pathol 14:321-334, 1990.
Chejfec C, Falkmer S, Askensten U, et al: Neuroendocrine tumors of the gastrointestinal tract. Pathol Res Pract 183:143-154, 1988.
Cox WF Jr., and Pierce B: The endodermal origine of the endocrine cells of an adenocarcinoma of the colon of the rat. Cancer 50:1530-1538, 1982.
Eusebi V, Mambelli V, Tison V, et al.: Endocrine differentation in basal cell carcinoma. Tumori 65:191-199, 1979.
Faverly DRGS, Manni JJ, Smedts, et al.: Adeno-carcinoid or Amphicrine Tumors of the Middle Ear a New Entity? Path Res Pract 188:162-171, 1992.
Feyrter F: Uber diffuse endokrine epitheliale Organe. Johann Ambrosius Barth, Leipzig, 1938.
Fontaine J, and LeDouarin NM: Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neuroectodermal origin of the cells of the APUD series. J Embryol Exp Morphol 41:209-222, 1977.
Golouh R, Us-Krasovec M, Auersperg M, et al.: Amphicrine — Composite Calcitonin and Mucin-Producing – Carcinoma of the Thyroid. Ultrastruct Pathol 8:197-206, 1985.
Gouzi J-L, Laigneau P, Delalande J-P, et al.: Indications for right hemicolectomy in carcinoid tumors of the appendix. Surg Gynecol Obstet 176:543-547, 1993.
Grace C, Yang H, Rotterdam H: Mixed, composite, Gladular- Endocrine Cell Carcinoma of the Stomach. Am J Surg Pathol. 15:592-598, 1991.
Hidvegi J, Zsolnai B, Szinay G: Amphicrine Tumor of the Vulva. Path Res Pract 183:505-508, 1988.
Hirt RS, Evans LD, Buroker RA, Oleson FB: Gastric enterochromaffin- like cell hyperplasia and neoplasia in the rat: an indirect effect of the histamine H2-antagonist BL-6341. Toxicol Pathol 16:273-287, 1988.
Itsuno M, Watanabe H, Iwafuchi M, et al.: Multiple carcinoids and endocrine cell micronests in type A gastritis. Their morphology, histogenesis, and natural history. Cancer. 63:881-890, 1989.
Kyung-Whan Min: Usefulness of Electron Microscopy in the Diagnosis of “Small” Round Cell Tumors of the Sinonasal Region. Ultrastruct Pathol 19:347-363, 1995.
Laine VJO, Ekfors TO, Gullichsen R, et al: Immunohistochemical characterization of an amphicrine mucinous islet-cell carcinoma of the pancreas. APMIS 100:335-340, 1992.
Lewin KJ: Carcinoid tumors and the mixed, composite, glandular- endocrine cell carcinomas. Am J Surg Pathol 11(Suppl 1): 71-86, 1987.
Mendelsohn G, De La Monte S, Dunn JL, et al: Gastric carcinoid tumors, endocrine cell hyperplasia, and associated intestinal metaplasia. Histologic, histochemical, and immunohistochemical findings. Cancer 60:1022-1031, 1987.
Muller K-M, Fisseler-Eckhoff A: What`s New in Lung Tumor Heterogeneity? Path.Res.Pract. 184:108-115, 1989.
Ordonez NG, Balsaver AM, Mackay B: Mucinous islet cell, amphicrine, carcinoma of the pancreas associated with watery diarrhea and hypokalaemia syndrome. Hum Pathol 19:1458- 1461, 1988.
Paladugu R, Nathwani B, Goodstein J, et al: Carcinoma of the larynx with mucosubstance production and neuroendocrine differentiation. Cancer 42:343-349, 1982.
Papadimitriou JC, Weihing RR, Choi C, et al: Prostatic Marker- Negative Amphicrine Carcinoma of the Prostate. Ultrastruct Pathol 18:357-363, 1994.
Pasquinelli G, Santini D, Preda P, et al.: Composite gastric carcinoma and precursor lesions with amphicrine features in chronic atrophic gastritis. Ultrastruct Pathol 17:9-24, 1993.
Ratzenhofer M: Uber enterale hyperplasien und Geschwulste der disseminerten endokrinen, parakrinen, Hellen Zellen Feyrters unter Berucksichtigung amphikriner Zellwucherungen. Verh Dtsch Ges Pathol. Tag Erlangen, 61:7-24, 1977.
Ratzenhofer M, Aubock L: The amphicrine, endo-exocrine, cells in the human gut, with a short reference to amphicrine neoplasias. Acta Morphologica Acad Sci Hung 28:37-58, 1980.
Poynter D, Pick CR, Harcourt RA, et al: Association of long lasting unsur-mountable histamine H2 blockade and gastric carcinoid tumors in the rat. Gut. 26:1284-1295, 1985.
Sakamoto F, Ito M, Matumura G, et al.: Ultrastructural study of a mucinous carcinoid of the skin J Cutan Pathol 18:128-133, 1991.
Schmid KO, Aubock L, Albegger K: Endocrine-Amphicrine Enteric Carcinoma of the Nasal Mucosa. Virchows Arch A Path Anat Histol 383:329-343, 1979.
Sheppard MN, Thurlow NP, Dewar A: Amphicrine Differentiation in Bronchiolo-alveolar Cell Carcinoma. Ultrastruct Pathol 18:437-441, 1994.
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Sjoblom SM, Sipponen P, Karonen SL, et al: Mucosal argyrophil endocrine cells in pernicious anaemia and upper gastrointestinal carcinoid tumors. J Clin Pathol 42:371-377, 1989.
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Watson PH, Alguacil-Garcia A: Mixed crypt cell carcinoma. A clinicopathological study of the so-called ”Goblet cell carcinoid” Virchows Arch A 412:175-182, 1987.
Wisniewski M, Toker C: Composite tumor of the gallbladder exhibiting both carcinomatous and carcinoidal patterns. Am J Gastroenterol 58:633-637, 1972.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 1999
VL 5
IS 3
BP 239
EP 244
PG 6
ER
PT J
AU Nagy, P
Jenei, A
Damjanovich, S
Jovin, MTh
Szolosi, J
AF Nagy, Peter
Jenei, Attila
Damjanovich, Sandor
Jovin, M Thomas
Szolosi, Janos
TI Complexity of Signal Transduction Mediated by ErbB2: Clues to the Potential of Receptor-Targeted Cancer Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE erbB proteins; erbB2; homoassociation; heteroassociation; breast cancer; Herceptin
ID erbB proteins; erbB2; homoassociation; heteroassociation; breast cancer; Herceptin
AB The erbB2 oncogene belongs to the type I trans-membrane tyrosine kinase family of receptors. Its medical importance stems from its widespread over-expression in breast cancer. This review will focus on the signal transduction through this protein, and explains how the overexpression of erbB2 may result in poor prognosis of breast cancer, and finally it will summerize our current understanding about the therapeutic potential of receptor-targeted therapy in breast cancer. ErbB2 does not have any known ligand which is able to bind to it with high affinity. However the kinase activity of erbB2 can be activated without any ligand, if it is overexpressed, and by heteroassociation with other members of the erbB family (erbB1 or epidermal growth factor receptor, erbB3 and erbB4). This interaction substantially increases the efficiency and diversity of signal transduction through these receptor complexes. In addition, erbB2 forms large scale receptor clusters containing hundreds of proteins. These receptor islands may take part in recruiting cytosolic factors which relay the signal towards the nucleus or the cytoplasm. Overexpression of erbB2 was linked to higher transforming activity, increased metastatic potential, angiogenesis and drug resistence of breast tumor in laboratory experiments. As a corollary of these properties, erbB2 amplification is generally thought to be associated with a poor prognosis in breast cancer patients. These early findings lead to the development of antibodies that down-regulate erbB2. Such a therapeutic approach has already been found effective in experimental tumor models and in clinical trials as well. Further understanding of the importance of erbB2 and growth factor receptors in the transformation of normal cells to malignant ones may once give us a chance to cure erbB2 over-expressing breast cancer.
C1 [Nagy, Peter] University Medical School of Debrecen, Department of Biophysics and Cell Biology, H4012 Debrecen, Hungary.
[Jenei, Attila] University Medical School of Debrecen, Department of Biophysics and Cell Biology, H4012 Debrecen, Hungary.
[Damjanovich, Sandor] University Medical School of Debrecen, Department of Biophysics and Cell Biology, H4012 Debrecen, Hungary.
[Jovin, M Thomas] Max Planck Institute for Biophysical Chemistry, Department of Molecular BiologyGottingen, Germany.
[Szolosi, Janos] University Medical School of Debrecen, Department of Biophysics and Cell Biology, H4012 Debrecen, Hungary.
RP Nagy, P (reprint author), University Medical School of Debrecen, Department of Biophysics and Cell Biology, H4012 Debrecen, Hungary.
CR Ahmad I, Longenecker M, Samuel J: Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. Cancer Res 53:1484-1488, 1993.
Alimandi M, Romano A, Curia MC, et al: Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 10: 1813-1821, 1995.
Allred DC, Clark GM, Molina R, et al: Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 23:974-979, 1992.
Allred DC, O’Connell P, Fuqua SA: Biomarkers in early breast neoplasia. J Cell Biochem Suppl 17G:125-131, 1993.
Andrulis IL, Bull SB, Blackstein ME, et al. neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol 16:1340-1349, 1998.
Bacus SS, Gudkov AV, Zelnick CR, et al: Neu differentiation factor, heregulin, induces expression of intercellular adhesion molecule 1: implications for mammary tumors. Cancer Res 53:5251-5261, 1993.
Bacus SS, Huberman E, Chin D, et al.: A ligand for the erbB- 2 oncogene product, gp30, induces differentiation of human breast cancer cells. Cell Growth Differ 3:401-411, 1992.
Bacus SS, Stancovski I, Huberman E, et al: Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res 52:2580- 2589, 1992.
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Barnes DM: c-erbB-2 amplification in mammary carcinoma. J.Cell Biochem Suppl 17G:132-138, 1993.
Baselga J, Norton L, Albanell J et al: Recombinant humanized anti-HER2 antibody, Herceptin, enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58:2825- 2831, 1998.
Baselga J, Seidman AD, Rosen PP, et al: HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology Huntingt 11:43-48, 1997.
Baselga J, Tripathy D, Mendelsohn J, et al: Phase II study of weekly intravenous recombinant humanized anti- p185HER2 monoclonal antibody in patients with HER2/neu- overexpressing metastatic breast cancer. J Clin Oncol 14:737-744, 1996.
Baulida J, Kraus MH, Alimandi M, et al: All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem 271:5251-5257, 1996.
Beerli RR, Hynes NE: Epidermal growth factor-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities. J Biol Chem 271: 6071-6076, 1996.
Benz CC, Scott GK, Sarup JC, et al: Estrogen-dependent, tamoxifen- resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24:85-95, 1993.
Berns EM, Foekens JA, van Staveren IL, et al: Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment. Gene 159:11-18, 1995.
Bianco AR, De Laurentiis M, Carlomagno C: 20 year update of the Naples Gun trial of adjuvant breast cancer therapy: evidence of interaction between c-erb-B2 expression and tamoxifene efficacy. Proc Am Soc Clin Oncol 17:97a1998.
Bourguignon LY, Zhu H, Chu A, et al: Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation. J Biol Chem 272:27913-27918, 1997.
Brower ST, Ahmed S, Tartter PI, et al: Prognostic variables in invasive breast cancer: contribution of comedo versus noncomedo in situ component. Ann Surg Oncol 2:440-444, 1995.
Burke CL, Stern DF: Activation of Neu, ErbB-2, mediated by disulfide bond-induced dimerization reveals a receptor tyrosine kinase dimer interface. Mol Cell Biol 18:5371-5379, 1998.
Campiglio M, Tagliabue E, Srinivas U, et al: Colocalization of the p185HER2 oncoprotein and integrin alpha 6 beta 4 in Calu- 3 lung carcinoma cells. J Cell Biochem 55:409-418, 1994.
Canman CE, Gilmer TM, Coutts SB, et al: Growth factor modulation of p53-mediated growth arrest versus apoptosis. Genes Dev 9:600-611, 1995.
Carraway KL, Sliwkowski MX, Akita R et al: The erbB3 gene product is a receptor for heregulin. J Biol Chem 269:14303- 14306, 1994.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 255
EP 271
PG 17
ER
PT J
AU Saleh, AH
Khatib, G
Jackson, H
Banerjee, M
AF Saleh, A Husain
Khatib, Ghada
Jackson, Hershel
Banerjee, Mousumi
TI Correlation of bcl-2 Oncoprotein Immunohistochemical Expression with Proliferation Index and Histopathologic Parameters in Colorectal Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colon carcinoma; adenoma; bcl-2; Ki-67; proliferation index; immunohistochemistry
ID colon carcinoma; adenoma; bcl-2; Ki-67; proliferation index; immunohistochemistry
AB Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004).The mean Ki67 labeling index (LI) was 30.05±7.6 and 38.12±11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.
C1 [Saleh, A Husain] Wayne State University, Department of PathologyDetroit, Michigan, USA.
[Khatib, Ghada] Wayne State University, Department of PathologyDetroit, Michigan, USA.
[Jackson, Hershel] Grace Hospital, Department of Medicine, Section of GastroenterologyDetroit, Michigan, USA.
[Banerjee, Mousumi] Wayne State University, Department of PathologyDetroit, Michigan, USA.
RP Saleh, AH (reprint author), Wayne State University, Department of Pathology, Detroit, USA.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 274
EP 279
PG 6
ER
PT J
AU Abd El All, H
Rye, A
Duvillard, P
AF Abd El All, Howayda
Rye, Annie
Duvillard, Pierre
TI p53 Immunohistochemical Expression of Egyptian Cervical Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical carcinoma; p53; FIGO staging
ID cervical carcinoma; p53; FIGO staging
AB Data concerning the expression of p53 in cervical carcinoma, one of the leading cause of death in developing countries, are still confusing. This study was designed to identify p53 in Egyptian cervical carcinoma in an attempt to evaluate its prognostic significance. Eleven chronic cervicitis and 38 invasive carcinoma (31 squamous cell carcinoma (sqcc) and 7 adenocarcinoma, ranging from stage IB to IVB), were stained with the monoclonal antibody anti p53, DO7, using the microwave for antigen retrieval. No immunoreactivity was detected in chronic cervicitis, while nuclear p53 reactivity was detected in all carcinoma and in squamous intra-epithelial lesions (SIL) overlying 8 sqcc. P53 immunohistochemical (IHC) expression was more pronounced in early clinical stages (p=0.007) and in adenocarcinoma compared to sqcc (p=0.015). A positive correlation was present between p53 and heat shock protein 70 (hsp70) expressions (p=0.005). No correlation could be found between p53 expression and tumor infiltrating lymphocytes, the presence or absence of either schistosomiasis or HPV infections. It can be concluded, that in the Egyptian population, p53 immunoreactivity appears to be an early event in cervical neoplasm, and seems to play an important role together with other cell regulatory proteins in the process of carcinogenesis, which could be different between sqcc and adenocarcinoma.
C1 [Abd El All, Howayda] Suez Canal University, Faculty of Medicine, Department of PathologyIsmailia, Egypt.
[Rye, Annie] Institute Gustave Roussy, Department of StatisticsVillejuif, France.
[Duvillard, Pierre] Institute Gustave Roussy, Department of PathologyVillejuif, France.
RP Abd El All, H (reprint author), Suez Canal University, Faculty of Medicine, Department of Pathology, Ismailia, Egypt.
EM howayda@intouch.com
CR Abd El All H, Prade M, Khatab T, et al: Immunological study of NK cells in cervical carcinoma. Ph.D. Thesis, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, 1992.
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Holm R, Skomedal H, Helland A, et al: Immunohistochemical analysis of p53 protein overexpression in normal, premalignant, and malignant tissues of the cervix uteri. J Pathol 169:21-26, 1993.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 280
EP 284
PG 5
ER
PT J
AU Dursun, AB
Memis, L
Dursun, A
Bayiz, H
Ozkul, M
AF Dursun, A Berna
Memis, Leyla
Dursun, Ayse
Bayiz, Hulya
Ozkul, Mine
TI Clinical Importance of Correlations Between p53 Immunoreactivity and Clinicopathological Parameters in Lung Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; lung cancer; clinicopathology
ID p53; lung cancer; clinicopathology
AB Many studies have revealed the frequency of p53 abnormalities in lung cancer. However, clinico-pathological studies of p53 abnormalities have yielded conflicting results. We examined the p53 immunoreactivity and studied the correlations of p53 status and clinicopathological parameters in 76 primary lung cancers. By using DO-7 antibody, different degrees of p53 immunoreactivity was detected in 8 of 30 small cell lung cancer (SCLC, 26.6%) and 22 of 46 non-small cell lung cancer (NSCLC, 47.8%), 6 of 19 adenocarcinoma, 16 of 27 epidermoid carcinoma cases. In the whole group, no correlation was detected between the p53 status and the histological types of tumor, local tumor invasion, nodal status, and distant metastasis and patient characteristics, such as age, gender or smoking habit. P53 status was also found to have no effect on survival. However, in the NSCLC group, there was a significantly higher p53 immunoreactivity in well- and moderately-differentiated tumors (p<0.05). Patients with p53 immunoreactivity had a poor therapeutic response in the whole group. We concluded that, although p53 immunreactivity may be found in NSCLC, this does not correlate with clinicopathological parameters except therapeutic response. In SCLC p53 immunreactivity can be negligible.
C1 [Dursun, A Berna] Ankara Ataturk Training and Research Hospital, Ergin sok. 43/4, Mebu-sevleri/Tandogan, 06580 Ankara, Turkey.
[Memis, Leyla] Gazi University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Dursun, Ayse] Gazi University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Bayiz, Hulya] Ankara Ataturk Training and Research Hospital, Ergin sok. 43/4, Mebu-sevleri/Tandogan, 06580 Ankara, Turkey.
[Ozkul, Mine] Ankara Ataturk Training and Research Hospital, Ergin sok. 43/4, Mebu-sevleri/Tandogan, 06580 Ankara, Turkey.
RP Dursun, AB (reprint author), Ankara Ataturk Training and Research Hospital, 06580 Ankara, Turkey.
EM ebdursun@superonline.com
CR Brambilla E, Gazzeri S, Moro D, et al: Immunohistochemical study of p53 in human lung carcinomas. Am J Pathol 143:199- 210, 1993.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 285
EP 290
PG 6
ER
PT J
AU Cserni, G
Vajda, K
Tarjan, M
Bori, R
Svebis, M
Baltas, B
AF Cserni, Gabor
Vajda, Kornel
Tarjan, Miklos
Bori, Rita
Svebis, Mihaly
Baltas, Bela
TI Nodal Staging of Colorectal Carcinomas from Quantitative and Qualitative Aspects. Can Lymphatic Mapping Help Staging?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal carcinoma; staging; sentinel lymph node; lymphatic mapping
ID colorectal carcinoma; staging; sentinel lymph node; lymphatic mapping
AB Retrospective data analysis was performed to determine the minimum number of lymph nodes required for the staging of colorectal carcinomas, and a prospective feasibility study was carried out to identify sentinel nodes in order to clarify whether these may predict the nodal status. From among 240 colorectal carcinoma specimens investigated between 1996 and 1998, 224 tumors were analyzed for their nodal status. Lymphatic mapping with vital patent blue dye injection into the peritumoral sub-serosal layer was performed in 25 patients. Blue nodes were identified by the pathologist in the unfixed specimen immediately after the resection of the bowel and were assessed separately. Of the 123 node-positive carcinomas, 40 had more than 3 nodes involved. The nodal positivity increased substantially when more than 6 nodes were assessed. The cumulative percentage analysis demonstrated that ideally 16 and 13 nodes should be obtained for the identification of any nodal involvement or the involvement of more than 3 nodes, respectively. Lymphatic mapping was successful in 24 patients (96%). Blue nodes were predictive of the nodal status in 19 cases (79%), and were the only sites of metastasis in 2 patients (15% of the node-positive cases). Lymphatic mapping with the vital blue dye technique does not seem to facilitate the staging of colorectal cancers, at least in our patient population with relatively large and deeply infiltrating tumors, and unless the technique is improved or other selective features of lymph nodes are found, all lymph nodes should be assessed. A minimum of 6 nodes, and an optimum of 16 nodes or more, are suggested from these series.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Vajda, Kornel] Bacs-Kiskun County Hospital, Department of SurgeryKecskemet, Hungary.
[Tarjan, Miklos] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Svebis, Mihaly] Bacs-Kiskun County Hospital, Department of SurgeryKecskemet, Hungary.
[Baltas, Bela] Bacs-Kiskun County Hospital, Department of SurgeryKecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
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Hermanek P, Giedl J, Dworak O: Two programmes for examination of regional lymph nodes in colorectal carcinoma with regard to the new pN classification. Path Res Pract 185:867- 873, 1989.
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Scott KWM, Grace RH: Detection of lymph node metastases in colorectal carcinoma before and after fat clearance. Br J Surg 76:1165-1167, 1989.
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Wolmark N, Fisher ER, Wieand HS, Fisher B and contributing NSABP investigators: The relationship of depth of penetration and tumor size to the number of positive nodes in Dukes C colorectal cancer. Cancer 53:2707-2712, 1984.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 291
EP 296
PG 6
ER
PT J
AU Kristt, D
Winston, JG
Mellov, MM
Veltman, V
Koren, R
AF Kristt, Don
Winston, J Ginger
Mellov, M Moshe
Veltman, Vladimir
Koren, Rumelia
TI Patterns of Proliferative Changes in Crypts Bordering Colonic Tumors: Zonal Histology and Cell Cycle Marker Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal carcinoma; colonic polyps; aberrant crypt foci; crypt replication cycles
ID colorectal carcinoma; colonic polyps; aberrant crypt foci; crypt replication cycles
AB Proliferative crypt changes have been noted in mucosa bordering colonic carcinomas, but their biological significance is disputed. We anticipated that zonal patterning of histological changes and cell cycle marker expression would provide clues to the pathogenesis of these border changes. 81 specimens were examined including carcinomas, adenomatours polyps, adenomas with early carcinoma, flat adenomas and aberrant crypt foci. The spatial distribution and frequency of micro-architectural features, and mucosal thickness were determined in a border domain of 150–300 sequential crypts/specimen. Immunocytochemical expression of Ki67 and p53 antigens in crypts also was semi-quantitatively examined. We found that in 100% of carcinomas two histologically abnormal zones (Proximate and Middle) separated tumor from normal mucosa. Differences in the feature frequency between zones were statistically significant (p<0.05). Both zones showed mild increases in crypt cell expression of Ki67, with a statistically significant relationship to zonal patterning (p<0.005). Weak expression of p53 only appeared in rare cells. Crypt elongation with mucosal thickening (1.9x normal, p<0.001) in the Proximate and Middle zones distinguished carcinomas from border changes in all benign lesions, except flat adenomas. Since this change occurs in all cases of carcinoma, there is no correlation with tumor stage or grade. Also in carcinomas, elaborate complexes of attached crypts (connected crypt structures) were characteristic of the Middle zone, so that proximate zone was always architecturally simpler. We conclude, that despite continuous carcinoma growth, the invaded border mucosa maintains a prototypical zonal organization of molecular and histological crypt changes This spatially organized reaction pattern is likely to reflect an interplay between regulated growth and destructive processes in response to advancing carcinoma. Compared to the edges of benign colonic tumors, the edges of carcinomas are distinctive and consistent enough to be diagnostically useful.
C1 [Kristt, Don] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Winston, J Ginger] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Mellov, M Moshe] Hasharon Hospital, Rabin Medical Center (Golda Campus), Department of Nuclear MedicinePetach Tikvah, Israel.
[Veltman, Vladimir] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
RP Koren, R (reprint author), A, Rabin Medical Center (Golda Campus), Department of Pathology, Petach Tikvah, Israel.
EM rumelia@isdnmail.co.il
CR Eide TJ: Remnants of adenomas in colorectal carcinomas. Cancer 51:1866-1872, 1983.
Muto T, Bussey H, Morson B: The evolution of cancer of the colon and rectum. Cancer 36:2251-2270, 1975.
Katada N, Hinder RA, Smyrk TC, et al: Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus. Arch Surg 132:728-733, 1997.
Bronner MP, Culin C, Reed JC, et al: The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 146:20-26, 1995.
Fenoglio C, Lane N: The anatomical precursor of colorectal carcinoma. Cancer 34:819-827, 1974.
Madara J, Harte P, Deasy J: Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium. Am J Pathol 110:230-235, 1983.
Shimoda T, Ikegami M, Fujisaki J, et al: Early colorectal carcinoma with special reference to its development de novo. Cancer 64:1138-1146, 1989.
Spratt JS Jr., Ackerman LV: Small primary adenocarcinomas of the colon and rectum. JAMA 179: 337-346, 1962.
Hamilton SR: The molecular genetics of colorectal neoplasia. Gastroenterology 105:3-7, 1993.
Saffos RO, Rhatigan RM: Benign, nonpolypoid, mucosal changes adjacent to carcinomas of the colon. Hum Pathol 8:441-449, 1977.
Dansky-Ullmann C, Salgaller M, Adams S, et al: Synergistic effects of IL-6 and IFN-gamma on cacinoembryonic antigen and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. Cytokine 7:118-129, 1995.
Brown LF, Berse B, Jackman RW, et al: Expression of vascular permeability factor, vascular endothelial growth factor, and it receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53:4727-4735, 1993.
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Roncucci L, Stamp D, Medline A, et al: Identification and quantification of aberrant crypt foci and microadenomas in the human colon. Hum Pathol 22:287-294, 1991.
Kristt D, Kingsley B, Cal R: Colonic aberrant crypts may originate from imparied fisstoning: relevance to increased risk of neoplasia. Human Pathol 30:1450-1462, 1999.
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Shpitz B, Bomstein Y, Mekori Y, et al: Aberrant Crypt foci in human colons: distribution and histomorphologic characteristics. Hum Pathol 29:469-475, 1998.
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Dervan PA, Magee HM, Carney DN: Proliferating cell nuclear antigen counts in formalin-fixed paraffin-embedded tissue correlate with Ki-67 in fresh tissue. Pathology Patterns. Am J Clin Pathol 97:S21-S25, 1992.
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Shi, SR:Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741-743, 1991
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Wong MH, Stappenbeck TS, Gordon JI: Living and commuting in intestinal crypts. Gastroenterol 116:208-210, 1999
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Park H-S, Goodlad RA, Wright NA: Crypt fission in the small intestine and colon: a mechanism for the emergence of G6PD locus-mutated crypts after treatment with mutagens. Am J Pathol 147:1416-1427, 1995.
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Bjerknes M, Cheng H, Hay K, et al: APC mutation and crypt cycle in murine and human intestine. Amer J Pathol 150:833- 839, 1997.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 297
EP 303
PG 7
ER
PT J
AU Rokkas, Th
Liatsos, Ch
Karameris, A
Petridou, E
Lazaris, A
Antoniades, D
Kalafatis, E
AF Rokkas, Theodore
Liatsos, Christos
Karameris, Andreas
Petridou, Evangeija
Lazaris, Andreas
Antoniades, Dimitris
Kalafatis, Evangeios
TI Proliferating Cell Nuclear Antigen (PCNA) Immunostaining in Helicobacter PyloriInfection: Impact of Eradication
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Helicobacter pylori infection; H. pylorieradication; PCNA immunostaining; gastric proliferation; gastric carcinogenesis
ID Helicobacter pylori infection; H. pylorieradication; PCNA immunostaining; gastric proliferation; gastric carcinogenesis
AB Despite the fact that the association of Helicobacter pylori (H. pylori)with an increased risk of gastric cancer has been well documented, the exact mechanisms of this association have not been fully elucidated. The aim of the present prospective study was to contribute to the exploration of these mechanisms by studying the relationship between H. pylori infection and proliferating cell nuclear antigen (PCNA) immunostaining in endoscopic biopsies in gastric antrum. Furthermore, we examined the impact of H. pylorieradication on this relationship. We studied 28 H. pyloripositive patients and the results were compared with 22 endoscopically and histologically normal H. pylorinegative patients (control group) who were comparable to the H. pyloripositive group for age and sex. In addition all H. pyloripositive patients were examined before and after treatment aiming to eradicate H. pylori. In the H. pylori(+) patients the median PCNA index was 35 (range 8-58) and this was significantly higher than the respective number in the control group [5.5 (2–14), p<0.001]. In patients studied before and after successful eradication of H. pylori(n=10) the corresponding numbers were 35 (8-56) and 7 (4–13) (p<0.01) the latter not being significantly different from the control group of H. pylori(-)patients. On the contrary, in patients without successful H. pylori eradication (n=18) the PCNA indices before and after treatment were similar [35.5 (21-58) vs 31.5 (20-56)]. It is concluded that H. pyloriinfection alters the replication cycle of the gastric mucosa inducing hyperproliferation, which return towards normal after successful H. pylori eradication.
C1 [Rokkas, Theodore] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Liatsos, Christos] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Karameris, Andreas] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Petridou, Evangeija] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Lazaris, Andreas] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Antoniades, Dimitris] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
[Kalafatis, Evangeios] 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 192B Alexandras Ave., 115 21 Athens, Greece.
RP Rokkas, Th (reprint author), 401 Army General Hospital, Gastroenterology Unit and Histopathology Laboratory, 115 21 Athens, Greece.
EM sakkor@compulink.gr
CR Marshall BJ, McGechie DB, Rogers PA, et al: Pyloric campylobacter infection and gastroduodenal disease. Med J Aust 142:439-444, 1985.
Rokkas T, Sladen G: Infection with campylobacter pylori. J Royal Coll Phys London 22:97-100, 1988.
Graham D: Campylobacter pylori and peptic ulcer disease. Gastroenterology 96:615-625, 1989.
Raws EA, Tytgat GNJ: Cure of duodenal ulcer associated with eradication of Helicobacter pylori. Lancet 335:1233-1235, 1990.
Tytgat GNJ, Lee A, Graham DY, et al: The role of infectious agents in peptic ulcer disease. Gastroenterol Internat 1993; 6:76-89, 1993.
Sipponen P, Kosunen TU, Valle J, et al: Helicobacter pylori infection and chronic gastritis in gastric cancer. J Clin Pathol 45:319-323, 1992
Graham D: Pathogenic mechanisms leading to Helicobacter pylori-induced inflammation. Eur J Gastroenterol Hepatol 4, suppl 2):S9-S16, 1992.
Forman D, Newell DG, Fullerton F, et al: Association between infection with H. pylori and risk of gastric cancer. Evidence from a prospective investigation. Brit Med J 302:1302-1305, 1991.
Parsonnet J, Friedman GD, Vandersteen DP, et al: H. pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127-1135, 1991
Nomura A, Stemmerman GN, Chyou PH, et al: H. pylori and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325:1132-1136, 1991
Talley NJ, Zinsmeister AR, Weaver A, et al: Gastric adenocarcinoma and H. pylori infection. J Natl Cancer Inst 83:1734-1739, 1991.
THE EUROGAST Study Group. An international association between Helicobacter pylori infection and gastric cancer: an international study. Lancet 341:1359-1362, 1993.
Hansson LE, Engstrand L, Nyren O, et al: Helicobacter pylori infection: Independent risk indicator of gastric adenocarcinoma. Gastroenterology 105:1098-1103, 1993.
International Agency for Research on Cancer. Schistosomes, liver flukes and Helicobacter pylori. Evaluation of carcinogenic risks to humans. IARC Monogr Eval Carcinog Risks Hum 61, 1994.
Correa P, Ruiz B, Shi TY, et al: Helicobacter pylori and nucleolar organizer regions in the gastric antral mucosa. Am J Clin Pathol 101:656-660, 1994.
Garcia RL, Coltrera MD, Gown AM: Analysis of proliferative grade using anti-PCNA / Cyclin in fixed, embedded tissues. Comparison with flow cytometric analysis. Am J Pathol 134:733-739, 1989.
Hall PA, Levison DA, Woods AL, et al: Proliferating cell nuclear antigen, PCNA, immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplams. J Pathol 162:285-294, 1990.
Woods AL, Hall PA, Shepherd NA, et al: The assessment of proliferating cell nuclear, PCNA, immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S+G2+M phase fraction, flow cytometric analysis, and prognosis. Histopathology 19:21-27, 1991.
Kamel OW, LeBrun DP, Davis RE, et al: Growth fraction estimation of malignant lymphomas in formalin-fixed paraffinembedded tissue using anti-PCNA / Cyclin 19A2. Correlation with Ki-67 labelling. Am J Pathol 138:1471-1477, 1993.
Battersby S, Anderson TJ: Correlation of proliferative activity in breast tissue using PCNA/Cyclin. Hum Pathol 21:781, 1990.
Coltrera MD, Gown AM: PCNA/Cyclin expression and BrdU uptake define different subpopulations in different cell lines. J Histochem Cytochem 39:23-30, 1991.
Marshall BJ, Francis G, Langton S, et al: Rapid urease test in the management of Campylobacter pyloridis associated gastritis. Am J Gastroenterol 3:200-210, 1987.
Potters HVPJ, Loffeld RJLF, Stobbeling E, et al: Rapid staining of Campylobacter pyloridis. Histopathology 11:1223, 1987.
Logan RP: Urea breath tests in the management of Helicobacter pylori infection. Gut 43, Suppl 1):S47-50, 1998.
Dixon MF, Genta RM, Yardley JH, et al: Classification and grading of gastritis. The updated Sydney system. Amer J Surg Pathol 20:1161-1181, 1996.
Motalsky H. Intuitive Biostatistics. Oxford University press. New York, Oxford, 1995.
Fraser AG, Sim R, Sankey EA, et al: Effect of eradication of Helicobacter pylori on gastric epithelial cell proliferation. Aliment Pharmacol Ther 8:167-173, 1994.
Cahill RJ, Xia H, Kilgallen C, et al: Effect of eradication of Helicobacter pylori infection on gastric epithelial cell proliferation. Dig Dis Sci 40:1627-1631, 1995.
Lynch DA, Mapstone NP, Clarke AM, et al: Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy. Gut 36:346-350, 1995.
Havard TJ, Sarsfield P, Wotherspoon AC, et al: Increased gastric epithelial cell proliferation in Helicobacter pylori-associated follicular gastritis. J Clin Pathol 49:68-71, 1996.
Bechi P, Balzi M, Beccioni A, et al:Helicobacter pylori and cell proliferation of the gastric mucosa: possible implications for gastric carcinogenesis. Am J Gasroenterol 91:271-276, 1996.
Chow KW, Bank S, Ahn J, et al: Helicobacter pylori infection does not increase gastric antrum mucosal cell proliferation. Am J Gastroenterol 90:64-66, 1995.
Peek RM Jr, Moss SF, Tham KT, et al: Helicobacter pylori cagA+ strains and dissosiasion of gastric epithelial cell proliferation from apoptosis. J Natl Cancer Inst 89:863-868, 1997.
Konturek PC, Bobrzynski A, Konturek SJ, et al: Epidermal growth factor and transforming growth factor alpha in duodenal ulcer and non-ulcer dyspepsia patients before and after Helicobacter pylori eradication. Scand J Gastroenterol 33:143-151, 1998.
Moss SF, Scholes JV, Holt PR: Abnormalities of epithelial apoptosis in multistep colorectal neoplasia demonstrated by terminal deoxyuridine nick end labeling. Dig Dis Sci 41:2238-2247, 1996.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 304
EP 308
PG 5
ER
PT J
AU Maity, P
Chakraborty, S
Bhattacharya, P
AF Maity, Putul
Chakraborty, Sunit
Bhattacharya, Pritha
TI Angiogenesis - a Putative New Approach in Glutamine Related Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; glutaminase; murine tumor
ID angiogenesis; glutaminase; murine tumor
AB Angiogenesis or the generation of new blood vessels, is an important factor regarding the growth of a tumor. Hence, it becomes a necessary parameter of any kind in therapeutic studies. Glutamine is an essential nutrient of tumor tissue and glutamine related therapy involves clearance of circulatory glutamine by glutaminase. So, whether this enzyme has any effect on angiogenesis of a tumor or not becomes an obvious question. To address this question, this study has been carried out with different murine tumor models.The results indicate that purified glutaminase reduces tumor volume as well as restricts the generation of new blood vessels. Glutaminase is effective in the case of solid as well as ascites tumor models. In the case of induced cancer, the host exhibits delayed onset of neoplasia following enzyme treatment and tumor host interactions determine the intensity of the neovascularisation process. Therefore, it can be concluded that this enzyme might be an effective agent against cancer metastasis.
C1 [Maity, Putul] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 700026 Calcutta, India.
[Chakraborty, Sunit] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 700026 Calcutta, India.
[Bhattacharya, Pritha] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 700026 Calcutta, India.
RP Maity, P (reprint author), Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 700026 Calcutta, India.
EM cncinstegiasceos@vsul.net.in
CR Bossi P, Viale G, Lee AK, et al: Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations. Cancer Res 55:5049- 5053, 1995.
Torry RJ, Rongish BJ: Angiogenesis in the uterus : potential regulation and relation to tumor angiogenesis. Amer J Reprod Immunol 27:171-179, 1992.
Folkman J, Shing Y: Angiogenesis. J Biol Chem 26:10931- 10934, 1992.
Goldie H, Felix MD: Growth characteristics of free tumor cells transferred serially in the peritoneal fluid of the mouse. Cancer Res 11:73-81, 1951.
Nagy JA, Morgan ES, Herzberg KT, et al: Pathogenesis of ascites tumor growth : angiogenesis, vascular remodelling and stroma formation in the peritoneal lining. Cancer Res 55:376- 385, 1995.
Miguez M, Davel L, Sacerdote de Lustig E: Lymphocyte-Induced Angiogenesis: Correlation with the metastatic incidence of two murine Mammary Adenocarcinomas. Invasion Metast 6:313- 320, 1986.
Folkman J: What is the role of angiogenesis in metastasis from Cutaneous Melanoma. Eur J Cancer Clin Oncol 23:361-363, 1987.
Netland PA, Zetter BR: Tumor-cell interactions with blood vessels during cancer metastasis. Fundamental Aspects of Cancer Dordrecht: Kluwer Academic Publishers. 84-97, 1989.
Greenblat M, Shubik P: Tumor Angiogenesis : Transfilter diffusion studies in the hamster by transparent chamber techniques. J Natl Cancer Inst 41:111-124, 1968.
Roberts J, Holcenberg JS, Dolowy WC: Antineoplastic activity of highly purified bacterial glutaminase. Nature 227:1136- 1137, 1970.
Maity P, Chakraborty S, Bhattacharya P, et al: Isolation and purification of phosphate dependent glutaminase from Sacoma- 180 tumor and its antineoplastic effects on murine model system. J Exp Clin Cancer Res, communicated).
Murphy ED: Studies in carcinogen induced carcinoma of the cervix in mice. Am J Pathol 29:608, 1953.
Murphy ED: Carcinogenesis of the uterine cervix in mice effect of diethylstilbestrol after limited application of 3-methylcholanthrene. J Natl Cancer Inst 27:611-653,1961.
Quesada AR, Sanchez-Jimenez F, Perez-Rodriguez J, et al: Purification of phosphate dependent glutaminase from isolated mitochondria of Ehrlich ascites tumor cells. Biochem J 256:1031- 1036, 1988.
Lund P: In methods of enzymatic analysis. Verlag Chemie: Weinheim 8:357-369, 1985.
Lowry OH, Rosenbrough NJ, Farr AL, et al: Protein measurements with folin phenol reagent. J Biol Chem 193:265-275, 1951
Danielsen T, Rofstad EK: VEGF, bFGF and EGF in the angiogenesis of human melanoma xenografts. Int J Cancer 76:836- 841, 1998.
Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4-6, 1990.
Burger MM, Folkman J: UICC study group on basic and clinical research: Tumor Angiogenesis. Int J Cancer 56:311-313, 1994.
Nagy JA, Brown LF, Senger DR, et al: Pathogenesis of tumor stroma generation : a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta 948:305-326,1998.
Dvorak HF, Harvey VS, Estrella P, et al: Fibrin containing gels induce angigenesis. Lab Invest 57:673-686, 1987.
Neidle A, Waelsch H: J Biol Chem 234:586, 1959.
Matar P, Celoria GC, Font MT, et al: Angiogenesis induced by tumor host interaction in the rat. J Exp Clin Cancer Res 16:249- 253, 1997.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 309
EP 314
PG 6
ER
PT J
AU Sarkady, E
Sapi, Z
Toth, V
Kiss, S
AF Sarkady, Emese
Sapi, Zoltan
Toth, Vera
Kiss, Sandor
TI Warthin-like Tumor of the Thyroid - a Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Warthin-like tumor; thyroid gland; papillary carcinoma; Hashimoto thyroiditis; metastasis
ID Warthin-like tumor; thyroid gland; papillary carcinoma; Hashimoto thyroiditis; metastasis
AB A case of Warthin-like tumor of the thyroid (WaLTT) with cervical lymph node metastasis is presented. The problems of the FNA diagnosis of this type of tumor is discussed as well as the histogenesis, nature and behaviour of this peculiar tumor.
C1 [Sarkady, Emese] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93, H-1091 Budapest, Hungary.
[Sapi, Zoltan] St John's Hospital, Department of PathologyBudapest, Hungary.
[Toth, Vera] St John's Hospital, Department of PathologyBudapest, Hungary.
[Kiss, Sandor] St. John Hospital, Department of SurgeryBudapest, Hungary.
RP Sarkady, E (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM se@korb2.sote.hu
CR Apel LR, Asa LS, Livolsi VA: Papillary Hurthle cell carcinoma with lymphocytic stroma. Am J Surg Pathol 19:810-814, 1995.
Jarry A, Cerf-Bensussan N, Brousse N, et al: Same peculiar subset of HML1+ lymphocytes present within normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas. Gut 29:1632-1638, 1988.
Kradin RL, Bhan AK: Tumor infiltrating lymphocytes. Lab Invest 69:635-638, 1993.
Okayashu I, Fujiwara M, Hara Y, et al: Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma . A study of surgical cases among Japanese, and white and African Americans. Cancer 76:2312-2318, 1995.
Ostrowski ML, Merino MJ: Tall cell variant of papillary thyroid carcinoma. A reassessment and immunohistochemical study with comparison to the ususal type of papillary carcinoma of thyroid. Am J Surg Pathol 20:964-974, 1996.
Ozaki O, Ito K, Mimura T, et al: Papillary carcinoma of the thyroid. Tall cell variant with extensive lymphocyte infiltration. Am J Surg Pathol 20:695-698, 1996.
Schroder S, Schwarz W, Rehpenning W, et al: Dendritic/Langerhans cells and prognosis in patients with papillary thyroid carcinomas: immunohistochemical study of 106 thyroid neoplasms correlated to follow-up data. J Clin Pathol 89:295-300, 1988.
Vera-Sempere FJ, Prieto M, Camanas A: Warthin-like tumor of the thyroid: a papillary carcinoma with mitochondrion-rich cells and abundant lymphoid stroma. A case report. Pathol Res Pract 194:341-347, 1998.
Wirtschafter A, Schmidt R, Rosen D, Kundu N, et al: Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto’s thyroiditis. Laryngoscope 107:95-100, 1997.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 315
EP 317
PG 3
ER
PT J
AU Jylling, BAM
Jorgensen, L
Holund, B
AF Jylling, Bak Anne Marie
Jorgensen, Lars
Holund, Berit
TI Mucinous Cystadenocarcinoma in Combination with Hemangiosarcoma in the Ovary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE ovary; cystadenocarcinoma; mucinous; hemangiosarcoma
ID ovary; cystadenocarcinoma; mucinous; hemangiosarcoma
AB The ovary is the sixth most frequent site of cancer in women in Denmark with an incidence of approximately 600 cases per year. Carcinomas predominate whereas sarcomas are rare. We describe a case of the combination mucinous cystadenocarcinoma and hemangiosarcoma in a 37-year old woman, who had a right-sited oophorectomy because of a cyst. Clinically there was no suspicion of malignancy. The macro- and microscopic findings are described as well as the immunohistochemical stainings performed to confirm the diagnosis. The case shows the importance of careful sampling at the macroscopic examination, especially from areas with a striking appearance.
C1 [Jylling, Bak Anne Marie] Odense University Hospital, Department of Pathology, Winsloewparken 15, DK-5000 Odense, Denmark.
[Jorgensen, Lars] Odense University Hospital, Department of Pathology, Winsloewparken 15, DK-5000 Odense, Denmark.
[Holund, Berit] Odense University Hospital, Department of Pathology, Winsloewparken 15, DK-5000 Odense, Denmark.
RP Jylling, BAM (reprint author), Odense University Hospital, Department of Pathology, DK-5000 Odense, Denmark.
EM anne.marie.bak.jylling@ouh.dk
CR Ongkasuwan C, Taylor J, Tang C: Angiosarcomas of the Uterus and Ovary: Clinicopathologic report. Cancer 49:1469-1475, 1982.
Nucci M, Krausz T, Lifschitz-Mercer B: Angiosarcoma of the ovary. Am J Surg Pathol 22:620-630, 1998.
Prat J, Scully R: Sarcomas in ovarian mucinous tumors. Cancer 44:1327-1331, 1979.
Prat J, Scully R: Ovarian mucinous tumors with sarcoma-like mural nodules. Cancer 44:1332-1344, 1979.
Haines & Taylor: Obstetrical and Gynaecological Pathology. Churchill Livingstone, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 318
EP 319
PG 2
ER
PT J
AU Lazaris, ChA
Paraskevakou, H
Davaris, SP
AF Lazaris, Ch Andreas
Paraskevakou, Helen
Davaris, S Panayiotis
TI A Solitary Cutaneous Tumor with Distinct Areas of Verruca and Seborrheic Keratosis-like Lesion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HPV; seborrheic keratosis; skin; in situ hybridization
ID HPV; seborrheic keratosis; skin; in situ hybridization
AB A single, exophytic, cutaneous tumor on the thigh of a 52-year-old man was examined by light microscopy, in situ hybridization and immunohistochemistry. It demonstrated distinct areas of verruca and of seborrheic keratosis-like morphology simultaneously. Focally, architectural abnormalities were noted in some deeper parts of the tumor, but there was no morphological evidence of malignancy. The patient has remained disease-free for two and a half years after surgery. Biotinylated full genomicDNA probes of HPV confirmed the presence of types 6/11 exclusively in the verrucous portion of the neoplasm. In the verrucous component p53 protein was overexpressed and, additionally, increased Ki-67 immunopositive signals were detected, being localized below the HPV-DNA-expressing spinous cells.
C1 [Lazaris, Ch Andreas] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Paraskevakou, Helen] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Davaris, S Panayiotis] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
RP Lazaris, ChA (reprint author), University of Athens, Medical School, Department of Pathology, GR-115 27 Athens, Greece.
EM alazaris@cc.uoa.gr
CR Jacyc WK, Dreyer L, de Villiers EM: Seborrheic keratoses of black patients with epidermodysplasia verruciformis contain human papillomavirus DNA. Am J Dermatopathol 15:1-6, 1993.
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Li J, Ackerman AB: "Seborrheic keratoses" that contain human papillomavirus are condylomata acuminata. Am J Dermatopathol 16:398-405, 1994.
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Payne DA, Sanchez R, Tyring SK: Cutaneous verruca with genital human papillomavirus in a 2 year-old girl. Am J Dermatopathol 19:258-260, 1997.
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Xia MY, Zhu WY, Lu JY, et al: Ultrastructure and human papillomavirus DNA in papillomatosis of external auditory canal. Int J Dermatol 35:337-339, 1996.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 1999
VL 5
IS 4
BP 320
EP 323
PG 4
ER
PT J
AU Robert, L
AF Robert, Ladislas
TI Cellular and Molecular Mechanisms of Aging and Age Related Diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE aging; matrix; cell communication
ID aging; matrix; cell communication
AB This review on aging is focused on those cellular and molecular mechanisms which concern age related pathologies. The central question addressed is the relationship between ''normal” aging and age-related pathologies such as osteoarthritis, cardiovascular diseases, emphysema, malignant tumors and cognitive decline, dementias. The mechanisms recognized as most important in cell and tissue aging are briefly outlined. Emphasis is laid on the importance of post-synthetic modifications of the macromolecules of the extracellular matrix and on cell matrix interactions. Loss of intercellular communication and cell-matrix interactions as a result of receptor decay and receptor uncoupling were recently recognized as key events. Unavoidable poly-pathology at advanced age may be the answer to the above question.
C1 [Robert, Ladislas] Universite de Pierre et Marie Curie, Laboratoire de Recherche sur les Therapeutiques Substitutives en Ophtalmologie, 6, Hotel-Dieu, 1 Place du Parvis Notre-Dame, 75181 Paris, Paris cedex 04., France.
RP Robert, L (reprint author), Universite de Pierre et Marie Curie, Laboratoire de Recherche sur les Therapeutiques Substitutives en Ophtalmologie, 75181 Paris, France.
CR Allal M, Robert L, Labat-Robert R: Fragmentation de la fibronectine dans la mucoviscidose. C R Acad Sci 314:587- 592, 1992.
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Bizbiz L, Alperovitch A, Robert L. et al: Aging of the vascular wall: serum concentration of elastin peptides and elastase inhibitors in relation with cardiovascular risk factor. The EVA study, Atherosclerosis 131:73-78, 1997.
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Faury G, Ristori MT, Verdetti J, et al: Effect of elastin peptides on vascular tone. J Vasc Res 32:112-119, 1995.
Fodil-Bourahla I, Drubaix I, Robert L: Effect of in vitro aging on the biosynthesis of glycosaminoglycans by human skin fibroblasts. Modulation by the elastin-laminin receptor. Mechanisms of Ageing and Development 106:241-260, 1999.
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Peterszegi G, Robert L: Cell death induced in lymphocytes expressing the elastin-laminin receptor by excess agonists: necrosis and apoptosis. Biomed & Pharmacother 52:369-377, 1998.
Peterszegi G, Tixier S, Robert L: Cell death by overload of the elastin-laminin receptor on human activated lymphocytes: protection by lactose and melibiose. Eur J Clin Invest 29:166-172, 1999.
Peterszegi G, Texier S, Robert L: Human helper and memory lymphocytes exhibit an inducible elastin-laminin receptor. Int Arch Allergy and Immunol 114:218-223, 1997.
Peterszegi G, Texier S, Robert AM, et al: Increased elastase and cathepsin G activity in activated lymphocytes from aged patients. Role of denutrition and dementia. Arch Gerontol Geriat 25:285-298, 1997.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 3
EP 9
PG 7
ER
PT J
AU Marchisone, Ch
Del Grosso, F
Masiello, L
Prat, M
Santi, L
Noonan, MD
AF Marchisone, Chiara
Del Grosso, Federica
Masiello, Luciana
Prat, Maria
Santi, Leonardo
Noonan, M Douglas
TI Phenotypic Alterations in Kaposi’s Sarcoma Cells by Antisense Reduction of Perlecan
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kaposi-sarcoma; perlecan; antisense
ID Kaposi-sarcoma; perlecan; antisense
AB Metastasis is a sequence of events including proliferation, migration, adhesion, invasion and subsequent metastatic growth of tumour cells in distant organs. We previously showed that highly metastatic variants of murine melanoma cells express higher levels of the basement membrane proteoglycan perlecan than low or non metastatic variants and expression of an antisense perlecan can reduce metastatic potential. In contrast, antisense expression of perlecan in fibrosarcoma cells was reported to enhance tumorigenesis. To better understand the role of perlecan in angiogenesis we have transfected KS-IMM, an immortalized cell line derived from a human Kaposi’s sarcoma, with an antisense perlecan construct and investigated the positive/negative role of perlecan in KS. KS-IMM cells were transfected with either empty vector (neo) or the antisense perlecan construct and clones were isolated. Immuno-blot analysis showed a reduction of perlecan levels in two (AP3 and AP4) isolated clones, in Northern blot analysis endogenous perlecan was undetectable in the AP3 and AP4 clones, while it was present in the neo control clones. AP clones had a reduced migration to HGF in Boyden chambers as compared to neo clones. Proliferation in low serum or serum-free conditions was strongly reduced in the AP clones as compared to the neo control cells. The neotransfected cells showed rapid proliferation in low serum supplemented with HGF and VEGF, while antisense transfected clones showed little response. Finally, AP-trasfected KS-IMM cells had significantly reduced migration to VEGF and HGF with respect to controls. In contrast, when the AP transfected cells were injected in nude mice they paradoxically showed enhanced tumor growth as compared to controls. Our preliminary data indicate that perlecan reduction plays a crucial role on Kaposi’s sarcoma cell migration and proliferation in vitro. However, in vivo KS-IMM depleted of perlecan had a growth advantage. A possible hypothesis is that perlecan is necessary for growth of KS-IMM cells in vitro, however its down-regulation might promote angiogenesis through increased angiogenic growth factor diffusion, resulting in enhanced tumor growth in vivo.
C1 [Marchisone, Chiara] Istituto Nazionale per la Ricerca sul Cancro, Modulo di Progressione Neoplastica, c/o Centro di Biotecnologie Avanzate, Largo Rosana Benzi, n. 10, 16132 Genova, Italy.
[Del Grosso, Federica] Centro di Biotecnologie AvanzateGenova, Italy.
[Masiello, Luciana] Istituto Nazionale per la Ricerca sul Cancro, Modulo di Progressione Neoplastica, c/o Centro di Biotecnologie Avanzate, Largo Rosana Benzi, n. 10, 16132 Genova, Italy.
[Prat, Maria] Universita del Piemonte Orientale A. Avogadro, Dep. of Medical Sciences, Laboratorio di IstologiaNovara, Italy.
[Santi, Leonardo] Istituto Nazionale per la Ricerca sul CancroGenova, Italy.
[Noonan, M Douglas] Istituto Nazionale per la Ricerca sul Cancro, Modulo di Progressione Neoplastica, c/o Centro di Biotecnologie Avanzate, Largo Rosana Benzi, n. 10, 16132 Genova, Italy.
RP Noonan, MD (reprint author), Istituto Nazionale per la Ricerca sul Cancro, Modulo di Progressione Neoplastica, 16132 Genova, Italy.
EM noonan@ermes.cba.unige.it
CR Adatia R, Albini A, Giunciuglio D, et al: Suppression of invasive behaviour of melanoma cells by stable expression of antisense perlecan cDNA. Annals Oncology 8:1257-1261, 1997.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 10
EP 17
PG 8
ER
PT J
AU Molnar, L
Berki, T
Hussain, A
Nemeth, P
Losonczy, H
AF Molnar, Lenke
Berki, Timea
Hussain, Alizadeh
Nemeth, Peter
Losonczy, Hajna
TI Detection of TNFa Expression in the Bone Marrow and Determinationof TNFa Production of Peripheral Blood Mononuclear Cells in Myelodysplastic Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myelodysplastic syndrome; MDS; apoptosis; TNFa
ID Myelodysplastic syndrome; MDS; apoptosis; TNFa
AB TNFa is a highly active cytokine which plays an important role in the regulation of apoptotic cell death, a mechanism involved in the pathophysiology of myelodysplastic syndrome (MDS). In this study we investigated the expression of TNFa of the bone marrow trephine biopsies by immunohistochemical method and the TNFa production of peripheral blood mononuclear cells by ELISA method in 15 patients affected by MDS. Five of seven patients without excess of blasts showed high or intermediate TNFa expression in the bone marrow biopsies, whereas two patients with excess of blasts were negative and one had low expression. The five CMML patients revealed low or intermediate expression. The production of TNFa by the PBMC was analysed in 10 patients, four patients with RA and two with CMML produced higher level of TNFa which increased after stimulation with phorbol myristic acetate, but none of the RAEB patients revealed increase in TNFa production. In conclusion we suppose that increased TNFa expression and production by PBMC may be an indirect evidence of the role of increased apoptosis in low risk MDS patients.
C1 [Molnar, Lenke] University of Pecs, I. Department of Internal Medicine, Ifjusag str. 13, 7624 Pecs, Hungary.
[Berki, Timea] University of Pecs, Faculty of Medicine, Department of Immunology and BiotechnologyPecs, Hungary.
[Hussain, Alizadeh] University of Pecs, I. Department of Internal Medicine, Ifjusag str. 13, 7624 Pecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and BiotechnologyPecs, Hungary.
[Losonczy, Hajna] University of Pecs, I. Department of Internal Medicine, Ifjusag str. 13, 7624 Pecs, Hungary.
RP Molnar, L (reprint author), University of Pecs, I. Department of Internal Medicine, 7624 Pecs, Hungary.
CR Alexandrakis M, Coulocheri S, Xylouri I, et al: Elevated serum TNF-a concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes. Haematologia 29:13-24, 1998.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 18
EP 23
PG 6
ER
PT J
AU Kato, Y
Frankenne, F
Noel, A
Sakai, N
Nagashima, Y
Koshika, Sh
Miyazaki, K
Foidart, JM
AF Kato, Yasumasa
Frankenne, Francis
Noel, Agnes
Sakai, Naoki
Nagashima, Yoji
Koshika, Shinri
Miyazaki, Kaoru
Foidart, Jean-Michel
TI High Production of SPARC/osteonectin/BM-40 in Mouse Metastatic B16 Melanoma Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SPARC; osteonectin; BM-40; melanoma; metastasis
ID SPARC; osteonectin; BM-40; melanoma; metastasis
AB Production of SPARC/osteonectin/BM-40 was determined in mouse B16 melanoma clones BL6 and F10 (high metastatic) and F1 (low metastatic). SPARC was produced greater amount in BL6 and F10 than in F1 cells, showing a good agreement with their metastatic potentials. Moreover, SPARC production was not influenced by culture pH, even in the acidic conditions (=pH 5.9). Although tumor tissues show often low pH due to excessive amount of acidic metabolites such as lactate, most studies have been done in neutral pH. High SPARC production in the acidic medium, therefore, is thought to be an important potential for tumor invasive behaviour.
C1 [Kato, Yasumasa] University of Liege, Faculty of Medicine, Laboratory of Tumor and Developmental BiologyLiege, Belgium.
[Frankenne, Francis] University of Liege, Faculty of Medicine, Laboratory of Tumor and Developmental BiologyLiege, Belgium.
[Noel, Agnes] University of Liege, Faculty of Medicine, Laboratory of Tumor and Developmental BiologyLiege, Belgium.
[Sakai, Naoki] Yokohama City University School of Medicine, Department of UrologyYokohama, Japan.
[Nagashima, Yoji] Yokohama City University School of Medicine, Department of PathologyYokohama, Japan.
[Koshika, Shinri] Kanagawa Dental College, Department of Biochemistry, 82 Inaoka-cho, 238-8580 Yokosuka, Japan.
[Miyazaki, Kaoru] Yokohama City University, Kihara Institute for Biological Research, Division of Cell BiologyYokohama, Japan.
[Foidart, Jean-Michel] University of Liege, Faculty of Medicine, Laboratory of Tumor and Developmental BiologyLiege, Belgium.
RP Kato, Y (reprint author), University of Liege, Faculty of Medicine, Laboratory of Tumor and Developmental Biology, Liege, Belgium.
EM yasumasa@kdcnet.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 24
EP 26
PG 3
ER
PT J
AU Ongrady, J
Laird, MH
Szilagyi, FJ
Horvath, A
Bendinelli, M
AF Ongrady, Joseph
Laird, M Helen
Szilagyi, F Joseph
Horvath, Attila
Bendinelli, Mauro
TI Unique Morphological Alterations of the HTLV-I Transformed C8166 Cells by Infection with HIV-1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE C8166; HIV-1; leukemia; surface projections; cellular mimicry; aberrant virions
ID C8166; HIV-1; leukemia; surface projections; cellular mimicry; aberrant virions
AB C8166 cells express T lymphocyte markers, a monocyte-specific esterase, taxpolypeptide of HTLV-I. In spite of this transactivator, their HIV-1 yield is low. Their culture conditions were modified, and infected cells were immobilized on a poly-L-lysine sheet under semisolid overlays to study their phenotypic alterations and HIV-1 production by microscopy and electron microscopy. Another lymphoid cultures (MT-4, CEM, CEM-ss, AdCEM) similarly treated were infected with either HIV-1/RF or IIIB. Specificity of HIV-1 was compared to the effects of vesicular stomatitis virus (VSV). Unlike other cultures, HIV-1/RF infected C8166 cells in Eagle’s MEM exhibited surface projections resembling hairy leukemia cells, which was followed by balloon degeneration and apoptosis. Immobilized HIV-1 infected cultures formed flat syncytia with several interdigitating dendritic projections. Syncytia shrunk with condensed nuclear material and axon-like filaments characteristic for infected macrophages. VSV induced enlargement and necrotic lysis of all cell types. Early postinfection with HIV-1, electron microscopy revealed irreversible membrane fusion above cell nuclei, and transient fusion between filaments. Transient presence of coated vesicles containing intact HIV-1 particles, Birbeck granule-like structures of Langerhans cells, fibrillar-lamellar structures resembling hairy leukemia or Sezary cells were detected. Late postinfection, high proportion of HIV-1 bud from polarized cytoplasm was empty particle, while that bud and entrapped in cytoplasmic vacuoles contained two or multiple cores in a fused envelope. The effect of early gene products of HIV-1 on HTLV-I and C8166 cells might elicit their latent potentials for monocyte or interdigitating dendritic cells, while in the later phase HTLV-I products might alter HIV-1 virion assembly.
C1 [Ongrady, Joseph] National Institute for Dermato-Venereology, Maria utca 41., 1085 Budapest, Hungary.
[Laird, M Helen] University of Glasgow, Department of Veterinary PathologyGlasgow, UK.
[Szilagyi, F Joseph] University of Glasgow, Institute of VirologyGlasgow, UK.
[Horvath, Attila] National Institute for Dermato-Venereology, Maria utca 41., 1085 Budapest, Hungary.
[Bendinelli, Mauro] University of Pisa, Department of BiomedicinePisa, Italy.
RP Ongrady, J (reprint author), National Institute for Dermato-Venereology, 1085 Budapest, Hungary.
EM ongjos@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 27
EP 37
PG 11
ER
PT J
AU Kaminska, J
Kowalska, M
Nowacki, PM
Chwalinski, M
Rysinska, A
Fuksiewicz, M
AF Kaminska, Janina
Kowalska, M. Maria
Nowacki, P Marek
Chwalinski, G. Maciej
Rysinska, Alicja
Fuksiewicz, Malgorzata
TI CRP, TNF-alpha, IL-1ra, IL-6, IL-8 and IL-10 in Blood Serum of Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; colorectal; cytokines; CRP
ID cancer; colorectal; cytokines; CRP
AB Blood serum cytokines: TNFa a, IL-1ra, IL-6, IL-8, IL-10 as well as CRP were investigated in patients with colorectal cancer, prior treatment and 1, 10 and 42 days after surgery. There was an increase of the levels of CRP, IL-6 and IL-10 in most patients 24 hours after surgery. The levels of IL-1ra were elevated in patients in stage C and in several patients in stage B of the disease and there was a decrease of circulating TNFa ain stage B patients. On day 10 and 42 after surgery, the levels of cytokines followed various patterns.
C1 [Kaminska, Janina] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Tumor Markers, Roentgen 5, 02-781 Warsaw, Poland.
[Kowalska, M. Maria] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Tumor Markers, Roentgen 5, 02-781 Warsaw, Poland.
[Nowacki, P Marek] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Colorectal CancerWarsaw, Poland.
[Chwalinski, G. Maciej] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Colorectal CancerWarsaw, Poland.
[Rysinska, Alicja] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Tumor Markers, Roentgen 5, 02-781 Warsaw, Poland.
[Fuksiewicz, Malgorzata] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Tumor Markers, Roentgen 5, 02-781 Warsaw, Poland.
RP Kaminska, J (reprint author), Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Tumor Markers, 02-781 Warsaw, Poland.
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Nakazaki H: Preoperative and postoperative cytokines in patients with cancer. Cancer 70:709-713, 1992.
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Young B, Gleeson M, Cripps AW: C-reactive protein: a critical review. Pathology 23:118-124, 1991.
Zhou D, Munster AM, Winchurch RA: Inhibitory effects of interleukin 6 on immunity. Possible implications in burn patients. Arch Surg 127:65-69, 1992.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 38
EP 41
PG 4
ER
PT J
AU Yasasever, V
Tas, F
Duranyildiz, D
Camlica, H
Kurul, S
Dalay, N
AF Yasasever, Vildan
Tas, Faruk
Duranyildiz, Derya
Camlica, Hakan
Kurul, Sidika
Dalay, Nejat
TI Serum Levels of the Soluble Adhesion Molecules in Patients with Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD 44; adhesion molecules; malignant melanoma
ID CD 44; adhesion molecules; malignant melanoma
AB The incidence of malignant melanoma has been steadily increasing over the past decades. CD 44 is a transmembrane glycoprotein which is implicated in a number of adhesive and migratory events. Downregulation of CD 44 is implicated in the metastatic process. P-Selectin is a member of the selectin family of cell surface molecules. The levels of P-Selectin in biological fluids may be elevated in subjects with a variety of pathological conditions. In malignant melanoma, elevation of the plasma level of soluble intercellular adhesion molecule-1 (sICAM-1) has been associated with a reduction in disease-free survival. This study was performed to investigate the differences in the serum concentrations of the adhesion molecules in patients with malignant melanoma.The study group consisted of 52 patients with malignant melanoma and 20 healthy subjects. No meaningful difference was observed for P-selectin and sICAM 1 levels. A statistically significant decrease was observed in the cancer patients for serum CD 44 levels.
C1 [Yasasever, Vildan] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Tas, Faruk] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Duranyildiz, Derya] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Camlica, Hakan] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Kurul, Sidika] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Dalay, Nejat] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
RP Dalay, N (reprint author), Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
EM ndalay@yahoo.com
CR Altemonte M, Colizzi F, Esposito G, et al: Circulating intercellular adhesion molecule 1 as a marker of disease progression in cutaneous melanoma. N Engl J Med 327-959, 1992.
Borland G, Ross JA, Guy K: Forms and function of CD 44. Immunology 9:139–148, 1998.
Guo YJ, Ma J, Wang JH, et al: Inhibition of human melanoma growth and metastasis in vitro by anti CD44 monoclonal antibody. Cancer Res 54:1561-1565, 1994.
Harning R, Mainolfi E, Bystryn JC, et al: Serum levels of circulating ICAM-1 in human melanoma. Cancer Res 51:5003- 5005, 1991.
Hart I, Birch M, Marshall JF:Cell adhesion receptor expression during melanoma progression and metastasis. Cancer Metastasis Rev 10:115-130, 1991.
Haynes BF, Hale LP, Patton KL, et al: Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate, CD44, in rheumatoid arthritis. Arthritis Rheum 34:1434-1443, 1991.
Herrlich P, Zoller M, Palls ST, et al: CD 44 splice variants: metastases meet lymphocytes. Immunol Today 14:395-399, 1993.
Kageshita T, Yoshii A, Kimura T, et al: Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. Cancer Res 53:4927-4932, 1993.
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Ley K, Tedder TF: Leukocyte interactions with vascular endothelium. New insights into selectin-mediated attachment and rolling. J Immunol 155:525- 530,1995.
Mackay CR , Terpe HJ , Stauder R , et al: Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 124:71-82, 1994.
Manten-Horst E, Danen EHJ, Smit L, et al: Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. Int J Cancer 64:182-188, 1995.
Nooijen PT, Westphal JR, Eggermont AM, et al: Endothelial PSelectin expression is reduced in advanced primary melanoma and melanoma metastasis. Am J Pathol 152:679-682, 1998.
Price EA, Coombe DR, Murray JC: Endothelial CD 44H mediates adhesion of a melanoma cell line to quiescent human endothelial cells in vitro. Int J Cancer 64:513-518, 1996.
Ristamaki R, Joensuu H, Jalkanen S: Does soluble CD44 reflect the clinical behavior of human cancer. Curr Top Microbiol Immunol 213:155-166, 1996.
Schadendorf D, Heidel J, Gawlik C, et al: Association with clinical outcome of expression of VLA-4 in primary cutaneous malignant melanoma as well as P-Selectin and E-Selectin on intratumoral vessels. J Natl Cancer Inst 87:366-371, 1995.
Schadendorf D, Diehl S, Zuberbier T, et al: Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage. Dermatology 192:89-93, 1996.
Sliutz G, Temfer C, Winkler S, et al: Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer. Br J Cancer 72:1494-1497, 1995.
Sy MS, Mori H, Liu D: CD44 as a marker in human cancers. Curr Opinion Oncol 9:108-112, 1997.
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Tedder TF: The selectins: Vascular adhesion molecules. FASEB J 9:866,1995.
Viac J, Gueniche A, Faure M, Claudy A. Soluble intercellular adhesion molecule 1 and malignant melanoma. Cancer Lett 72:191-194,1993.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 42
EP 45
PG 4
ER
PT J
AU Karak, KA
Singh, R
Tandon, NP
Sarkar, Ch
AF Karak, Kumar Asis
Singh, Rajvir
Tandon, N Prakash
Sarkar, Chitra
TI A Comparative Survival Evaluation and Assessment of Interclassification Concordance in Adult Supratentorial Astrocytic Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Brain tumors; astrocytic tumors; classification; grading; survival
ID Brain tumors; astrocytic tumors; classification; grading; survival
AB Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults (³ ³16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease.
C1 [Karak, Kumar Asis] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Singh, Rajvir] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Tandon, N Prakash] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarcs@hotmail.com
CR Burger PC, Scheithauer BW: Tumors of the central nervous system. In: Atlas of Tumor Pathology, Third series, Fascicle 10. Eds. Rosai J, Sobin LH. Armed Forces Institute of Pathology, Washington DC, 1994.
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Daumas-Duport C, Scheithauer B, O’Fallon J, et al:Grading of astrocytomas. A simple and reproducible method. Cancer 62:2152-2165, 1988.
Garcia DM, Fulling KH, Marks JE: The value of radiation therapy in addition to surgery for astrocytomas of the adult cerebrum. Cancer 55:919-927, 1985.
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Kim TS, Halliday AL, Hedley-Whyte ET, et al: Correlates of survival and the Daumas-Duport grading system for astrocytomas. J Neurosurg 74:27-37, 1991.
Kleihues P, Burger PC, Scheithauer BW: Histological typing of tumors of the central nervous system. New York: Springer-Verlag, 1993.
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Sharma S, Karak AK, Sarkar C, et al: A grading study of gliomas using computer aided malignancy classification and histologic morphometry. J Neuro-Oncol 27:75-85, 1996.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 46
EP 52
PG 7
ER
PT J
AU Nemeth, Zs
Somogyi, A
Takacsi-Nagy, Z
Barabas, J
Nemeth, Gy
Szabo, Gy
AF Nemeth, Zsolt
Somogyi, Andras
Takacsi-Nagy, Zoltan
Barabas, Jozsef
Nemeth, Gyorgy
Szabo, Gyorgy
TI Possibilities of Preventing Osteoradionecrosis During Complex Therapy of Tumors of the Oral Cavity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumors of the oral cavity; mandibular resection; radiotherapy; osteoradionecrosis; prevention
ID Tumors of the oral cavity; mandibular resection; radiotherapy; osteoradionecrosis; prevention
AB In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or postoperative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.
C1 [Nemeth, Zsolt] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria u. 52., H-1085 Budapest, Hungary.
[Somogyi, Andras] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Takacsi-Nagy, Zoltan] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Barabas, Jozsef] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria u. 52., H-1085 Budapest, Hungary.
[Nemeth, Gyorgy] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Szabo, Gyorgy] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria u. 52., H-1085 Budapest, Hungary.
RP Nemeth, Zs (reprint author), Semmelweis University, Department of Oral and Maxillofacial Surgery, H-1085 Budapest, Hungary.
CR Aitasalo K, Niinikoski J, Grenman R, et al: A modified protocol for early treatment of osteomyelitis and osteoradionecrosis of the mandible. Head-Neck 20:411-417, 1988.
Bachmann G, Rossler R, Klett R, et al: The role of magnetic resonance imaging and scintigraphy in the diagnosis of pathologic changes of the mandible after radiation therapy. Int J Oral Maxilofac Surg 25:189-195, 1996.
Behar RA, Martin PJ, Fee WE, et al: Irridium-192 interstitial implant and external beam radiation therapy in the management of squamous cell carcinomas of the tonsil and soft palate. Int J Radiat Oncol Biol Physics 28:221-227, 1994.
Bras J, Jonge de HKT, Merkesteyn JPR: Osteoradionecrosis of the mandible: pathogenesis. Amer J Otolaryngology 11:244- 250, 1990.
Epstein JB, Mc Bride BC, Stevenson-Moore P, et al: The efficacy of chlorhexidine gel in reduction os Streptocossus mutans and Lactobacillis species in patients treated with radiation therapy. Oral Surgery, Oral Medicine, Oral Pathology 71:172-178, 1991.
Happonen RR, Viander M, Pelliniemi L, et al: Actinomyces israelii in osteoradionecrosis of the jaws. Histopathologic and immunocytochemical study of five cases. Oral Surgery, Oral Medicine, Oral Pathology 55:580-588, 1983.
Hartmann A, Almeling M, Carl UM: Hyperbaric oxygenation, HBO, in the treatment of radiogenic side effects. Strahlenther Oncol 172:641-648, 1996.
Hermans R, Fossion E, Ioannides C, et al: CT findings in osteoradionecrosis of the mandible. Skeletal Radiol 25:31-36, 1988.
Horiot JC, Bone MC, Ibrahim E, et al: Systemic dental management in head and neck irradiation. Int J Radiat Oncol Biol Physics 7:1025-1029, 1981.
Jesse RH, Fletcher GH, Lindberg RD, et al: Cancer of the head and neck. In Cancer Patient Care at M.D. Anderson Hospital and Tumor Institute, ed. by Clark RL and Howe CD Chicago, Yearbook Medical Publishers, Inc. 92-93, 1976.
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McKenzie MR, Wong FLW, Epstein JB, et al: Hyperbaric oxygen and postradiation osteonecrosis of the mandible. Oral Oncology, European J Cancer 29B:201-207, 1993.
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Morton ME: Osteoradionecrosis : A study of the incidence in the North West of England. Br J Oral Maxillofacial Surgery 24: 323-331, 1986
Murray CG, Herson J, Daly TE, et al: Radiation necrosis of the mandible: A 10 year study. Part I. Factors Influencing the onset of necrosis. Int J Radiat Oncol Biol Physics 6:543-548, 1980.
Murray CG, Herson J, Daly TE, et al: Radiation necrosis of the mandible: A 10 year study. Part II. Dental factors; Onset, duration and management of necrosis. Int J Radiat Oncol Biol Physics 6:549-553, 1980.
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Santamaria E, Wei FC, Chen HC: Fibula osteoseptocutaneous flap for reconstruction of osteoradionecrosis of the mandible. Plast Reconstr Surg 101:921-929, 1998.
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Szabo G, Kovacs A, Dori F: Behandlung der Osteoradionekrose im Unterkieferbereich. Septische Mund-Kiefer-Gesichtschirurgie, Band XXIX. Georg Thieme Verlag, Stuttgart, New York 138-140, 1984.
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van Merkesteyn JPR, Bakker DJ, Borgmeijer-Hoelen AMMJ: Hyperbaric oxygen treatment of osteoradionecrosis of the mandible. Experience in 29 patients. Oral Surgery, Oral Medicine, Oral Pathology 80:12-16, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 53
EP 58
PG 6
ER
PT J
AU Elpek, G
Gelen, T
Aksoy, HN
Karpuzoglu, T
Keles, N
AF Elpek, Ozlem Gulsum
Gelen, Tekinalp
Aksoy, Hikmet Nazif
Karpuzoglu, Tuncer
Keles, Nuran
TI Microvessel Count, Proliferating Cell Nuclear Antigen and Ki-67 Indices in Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microvessel count; angiogenesis; proliferation; gastric carcinoma
ID microvessel count; angiogenesis; proliferation; gastric carcinoma
AB The aim of the present study was to immunohistochemically investigate the prognostic value of neovascularization (expressed as microvessel count-MVC) and tumor cell proliferation (expressed as PCNA labeling index – PLI and Ki-67 labeling index – KLI) in gastric adenocarcinoma. Correlations with clinicopathologic features were also evaluated. Tumor specimens from 74 patients diagnosed as gastric adenocarcinoma were included in this study. Formalin fixed, paraffin embedded tissue sections stained immunohistochemically with F-VIII, PC10 and MIB-1 monoclonal antibodies. By ocular grid subdivided into 100 areas, number of microvessels and PC10, MIB-1 positive and negative cells were counted at x400 magnification. Chi-square test, Kaplan-Meier method and cox regression analysis were used for statistical analysis. The results showed that, MVC and PLI had a significant correlation with invasion and lymph node metastasis. The prognosis was significantly worse in patients with high MVC (>14 ) and with high PLI (>49%). However any relationship was not observed between KLI (38%) and clinicopathologic parameters, so KLI failed to predict the prognosis. Cox model showed that, MVC and PLI were independent prognostic variables. Ki-67 labeling index in gastric carcinomas has no prognostic relevance. However, the evaluation of microvessel count and proliferating cell nuclear antigen index in gastric carcinomas could be reliable indicators of prognosis.
C1 [Elpek, Ozlem Gulsum] Akdeniz University, Faculty of Medicine, Department of Pathology, Typ Fakultesi, Patoloji ABD, Yeni Typ, Dekanlyk, 07070 Antalya, Turkey.
[Gelen, Tekinalp] Akdeniz University, Faculty of Medicine, Department of Pathology, Typ Fakultesi, Patoloji ABD, Yeni Typ, Dekanlyk, 07070 Antalya, Turkey.
[Aksoy, Hikmet Nazif] Akdeniz University, Faculty of Medicine, Department of Pathology, Typ Fakultesi, Patoloji ABD, Yeni Typ, Dekanlyk, 07070 Antalya, Turkey.
[Karpuzoglu, Tuncer] Akdeniz University, Medical School, Department of General SurgeryAntalya, Turkey.
[Keles, Nuran] Akdeniz University, Faculty of Medicine, Department of Pathology, Typ Fakultesi, Patoloji ABD, Yeni Typ, Dekanlyk, 07070 Antalya, Turkey.
RP Elpek, G (reprint author), Akdeniz University, Faculty of Medicine, Department of Pathology, 07070 Antalya, Turkey.
EM elpek@hipokrat.med.akdeniz.edu.tr
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Ramires M, David L, Leitao D: Ki-67 Labelling index in gastric carcinomas. An immunohistochemical study using double staining for the evaluation of the proliferatif activity of diffusetype carcinomas. J Pathol 182: 62- 67, 1997
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Rudas M, Gnant MFX, Mittlboeck M: Thymidine labeling index and Ki-67 growth fraction in breast cancer: Comparison and correlation with prognosis. Breast Cancer Res Treat 32:165-75, 1994.
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Tanigawa N, Amaya N, Matsumura M: Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res 56:2671-2676, 1996.
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Toschi L, Bravo R: Changes in cyclin/PCNA distribution during DNA repair synthesis. J Cell Biol 107:1623-1628, 1988.
Vermeulen PB,Verhoeven D, Hubens G: Microvessel density, endothelial cell proliferation and tumor cell proliferation in human colorectal adenocarcinomas. Ann Oncol 6:59-64, 1995.
Victorzon M, Roberts PJ, Hanglund C: Ki-67 immunoreactivity, ploidy and S-Phase fraction as prognostic factors in patients with gastric carcinoma. Oncology 53:182-191, 1996.
Weidner N: Tumor Angiogenesis: Review of current applications in tumor prognostication. Semin Diag Pathol. 10:302-313, 1993.
Xiangming C, Hokita S, Natsugoe S: Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer. Ann Surg Oncol 5:585-589, 1998.
Yonemura Y, Ohyama S, Sugiyama K: Growth fractions in gastric carcinomas determined with monoclonal antibody Ki-67. Cancer 65:1130-1134, 199.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 59
EP 64
PG 6
ER
PT J
AU Kristt, D
Turner, I
Koren, R
Ramadan, E
Gal, R
AF Kristt, Don
Turner, Isaac
Koren, Rumelia
Ramadan, Edward
Gal, Rivka
TI Overexpression of Cyclin D1 mRNA in Colorectal Carcinomas and Relationship to Clinicopathological Features: An In Situ Hybridization Analysis*
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cyclin D1; in situ hybridization; mRNA; colon cancer; colorectal carcinoma; survival; grade; stage
ID cyclin D1; in situ hybridization; mRNA; colon cancer; colorectal carcinoma; survival; grade; stage
AB Increased expression of a key cell cycle regulator, cyclin D1, may have relevance to carcinogenesis and clinicopathological characteristics of some cancers. This study represents the first application of in situ hybridization, ISH, to detect cyclin D1 mRNA in tissue sections from colorectal carcinomas. This approach was selected because of its unique potential to clarify whether increased expression of cyclin D1 mRNA correlates with clinical and pathological parameters. The ISH ofa non-radioactive oligonucleotide probe (Biogenex) was immunocytochemically detected in paraffin embedded sections from biopsy or resection specimens. Tumors ranged from well to poorly differentiated, and from stages A, B, C, and D. Ten year survival data were available on the majority of patients. Intensity of tumor and background (smooth muscle) signals were independently scored from 0 to 3. Overexpressed cyclin D1 mRNA was seen in 86% of cases compared to background. This frequency is similar to that reported for pancreatic carcinoma. The average signal intensity score in tumor foci was 1.9 with a background score of 0.05 (p<001). All cases showed specific staining judged by the cytoplasmic localization and a tumor signal:background ratio > 1. Expression did not differentiate cancers based on grade, stage or survival (p>1), but did differentiate carcinoma and severe dysplasia from mild dysplasia. We conclude that ISH of cyclin D1 mRNA is an effective and relatively specific means of detecting activity of this gene in colonic neoplasms. The high frequency of overexpression implies that gene activity by itself is not likely to predict a tumor’s biological or clinical behavior. On the other hand, these data suggest that increased cyclin D1 gene activity may be an early event in colorectal carcinogenesis. They also are consistent with findings showing cyclin D1 is inducible by a variety of oncogene products.
C1 [Kristt, Don] A, Rabin Medical Center (Golda Campus), Department of Pathology, HaSharon HospitalPetach Tikvah, Israel.
[Turner, Isaac] A, Rabin Medical Center (Golda Campus), Department of Pathology, HaSharon HospitalPetach Tikvah, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of SurgeryPetach Tikvah, Israel.
[Ramadan, Edward] A, Rabin Medical Center (Golda Campus), Department of SurgeryPetach Tikvah, Israel.
[Gal, Rivka] A, Rabin Medical Center (Golda Campus), Department of Pathology, HaSharon HospitalPetach Tikvah, Israel.
RP Kristt, D (reprint author), A, Rabin Medical Center (Golda Campus), Department of Pathology, Petach Tikvah, Israel.
EM pdkristt@netvision.net.il
CR Alperts B, Bray D, Lewis J, et al: Molecular biology of the cell. 2nd ed. Garland Publ, New York-London, 481-549, 1989.
Arber N, Hibshoosh H, Moss SF, et al: Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis. Gastroenterology 110:669-674, 1996.
Bartkova J, Lukas J, Strauss M, et al: The PRAD-1/cyclin D1 oncogene product accumulates aberrantly in a subset of colorectal carcinomas. Int J Cancer 58:568-573, 1994.
Bartkova J, Lukas J, Strauss M, et al: Cell cycle-related variation and tissue restricted expression of human cyclin D1 protein. J Pathol 172:237-245, 1994.
Bates S, Bonetta L, MacAllan D, et al: CDK6, PLSTIRE, and CDK4, PSK-J3, are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene 9:71-79, 1994.
Betticher D, Heighway J, Hasleton PS, et al: Prognostic significance of CCND1, cyclin D1, overexpression in primary resected non-small-cell lung cancer. Br J Cancer 73:294-300, 1996.
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Chen X, Bargonetti J, Prives C: p53, through p21, WAF1/CIP1), induces cyclin D1 synthesis. Cancer Res. 55:4257-4263, 1995.
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Sutter T, Doi S, Carnevale KA, et al: Expression of cyclins D1 and E in human colon adenocarcinomas. J Med 28:285-309, 1997.
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Zhou P, Jiang W, Zhang Y-J, et al: Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells. Oncogene 11:571-580, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 65
EP 70
PG 6
ER
PT J
AU Nemes, B
Zalatnai, A
Podder, H
Jaray, J
Sotonyi, P
Schaff, Zs
Foldes, K
Perner, F
AF Nemes, Balazs
Zalatnai, Attila
Podder, Hemangshu
Jaray, Jeno
Sotonyi, Peter
Schaff, Zsuzsa
Foldes, Katalin
Perner, Ferenc
TI Papillary Microcarcinoma of the Thyroid Gland in Renal Transplant Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE papillary microcarcinoma; thyroid cancer; immunosuppression; renal transplantation
ID papillary microcarcinoma; thyroid cancer; immunosuppression; renal transplantation
AB Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31th of August 1999 1709 cadaver renal allograft transplantations were perfomed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature papillary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieve even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.
C1 [Nemes, Balazs] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Podder, Hemangshu] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Jaray, Jeno] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Sotonyi, Peter] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Foldes, Katalin] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
RP Nemes, B (reprint author), Semmelweis University, Department of Transplantation and Surgery, H-1082 Budapest, Hungary.
EM nemes@mailtrans.sote.hu
CR Auteliano F, Spagnoli LG, Santeusinaio G, et al: Occult carcinoma of the thyroid gland: an epidemiological study of autopsy material. Ann Ital Chir 61:141-146, 1990.
Brunner FP, Landais P, Selwood NH: Malignancies after renal transplantation: the EDTA-ERA registry experience. European Dialysis and Transplantation Association-European Renal Association. Nephrol Dial Transplant 10:74-80,, suppl 1), 1995.
Buccianti G, Maisonneuve P, Ravasi B, et al: Cancer among patients on renal replacement therapy: a population based survey in Lombardi, Italy. Int J Cancer 66:591-593, 1996.
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Fahey TJ3rd, Reeve TS, Delbridge L: Increasing incidence and changing presentation of thyroid cancer over a 30 year period. Br J Surg 82:518-20, 1995.
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Penn I: Neoplastic complications of transplantation. Semin Respir Infect 8:233-239, 1993.
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Torre G, Borgonovo G, Amato A, et al: Differentiated thyroid cancer: surgical treatment of 190 patients. Eur J Surg Oncol 22:276- 281, 1996.
Woolner LB, Beahrs OH, Black BM, et al:Classification and prognosis of thyroid carcinoma. A study of 885 cases observed in a thirty year period. Am J Surg 102:354-387, 1981.
Yamamoto Y, Maeda T, Izumi K, et al: Occult papillary carcinoma ot the thyroid. Cancer 65:1173-1179, 1990.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2000
VL 6
IS 1
BP 72
EP 75
PG 4
ER
PT J
AU Timar, J
Toth, J
AF Timar, Jozsef
Toth, Jeannette
TI Tumor Sinuses - Vascular Channels
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE tumor sinus; vascular channel; melanoma; breast cancer; pathomechanism
ID tumor sinus; vascular channel; melanoma; breast cancer; pathomechanism
AB The existence of tumor cell-lined sinuses (vascular channels) in various experimental and human cancer is known for almost a half a century described by a Hungarian pathologist, Bela Kellner. Meanwhile, even the existence as well as the pathomechanism and the possible functional significance of these sinuses are heavily challenged in the recent literature. Ultrastructural studies however provide evidence for the presence of tumor cell-lined sinuses in human melanoma and breast cancer. The generation of such sinuses can be suggested in two ways: by de novoformation, when tumor cells recapitulate an embryonic geno- and phenotype by reexpressing endothelial genes or by a secondary mechanism, where the incorporated microvessels degenerate due to the predominant expression of anti-angiogenic factors. Literature data are available for the potential diagnostic and clinical significance of the tumor sinuses (vascular channels) stimulating further studies on this issue.
C1 [Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Budapest, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Toth, Jeannette] Semmelweis University, Department of OphthalmologyBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182-1186, 1971.
Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353-364, 1996
Bergers G, Javaherian K, Folkman J, et al: Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284:808-812,1999.
Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739-752, 1999.
Folberg R, Hendrix MJ, Maniotis AJ: Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 156:361-381, 2000.
Hendrix MJC, Seftor EA, Seftor REB, et al. Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/ scatter factor, HGF/SF). Am J Pathol 152:855-863, 1998.
McDonalds DM, Munn L, Jain RK:Vasculogenic mimicry: how convincing, how novel, and how significant. Am J Pathol 156:383-388, 2000.
Barinaga M: A face-off over tumor blood supply. Science 287:783-785, 2000.
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Warren BA, Shubik P: The growth of the blood supply to melanoma transplants in the hamster cheek pouch. Lab Invest 15:464-478,1966.
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Wesseling P, van der Laak JA, de Leeuw H, et al. Quantitative immunohistological analysis of the microvasculature in untreated human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor sections. J Neurosurg 81:902-909, 1994.
Holmgren L, O’Reilly MS, Folkman J: Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149-153,1995.
Pezzella F, Pastorino U, Tagliabue E, et al. Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Am J Pathol 151:1417-1423, 1997.
Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994-1998, 1999.
Folberg R, Pe’er J, Gruman LM, et al: The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched casecontrol study. Hum Pathol 23:1298-1305,1992.
Folberg R, Fleck M, Mehaffey MG, et al: Mapping prognostically significant vascular patterns in ciliary body and choroidal melanomas. Pathol Oncol Res 2:229-236,1996.
Bissell MJ: Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch – a rose by any other name? Am J Pathol 155:675-679,1999.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 83
EP 86
PG 4
ER
PT J
AU Cox, G
Walker, AR
Muller, S
Abrams, RK
Steward, PW
O’Byrne, JK
AF Cox, Giles
Walker, A Rosemary
Muller, Salli
Abrams, R Keith
Steward, P William
O’Byrne, J Kenneth
TI Does Immunointensity Account for the Differences in Prognostic Significance of Bcl-2 Expression in Non-Small Cell Lung Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bcl-2; apoptosis; prognosis; non-small cell lung cancer
ID Bcl-2; apoptosis; prognosis; non-small cell lung cancer
AB Bcl-2 is an oncogenic protein that plays a central role in apoptosis. The association of Bcl-2 expression and prognosis in non-small cell lung cancer (NSCLC) is unclear, with some studies showing improved outcome whilst others show no survival advantage. We evaluated 178 surgically resected NSCLC specimens for Bcl-2 and p53 immunoexpression. Bcl-2 staining was present in 34.9% of cases (weakly staining 24.2%, strongly staining 10.7%), nuclear p53 in 43.3% and cytoplasmic p53 in 10.7%. There was no association between p53 and survival. Bcl-2 immunoexpression correlated with improved outcome (p=0.04). A sub-group of strongly Bcl-2 staining cases had a poor survival compared to those that stained weakly (p=0.01). The strongly staining cases had a similar survival to negative cases. Immunointensity may therefore account for the disparity in results regarding the prognostic significance of Bcl-2 demonstrated in previous studies.
C1 [Cox, Giles] Leicester Royal Infirmary, Department of Medical Oncology, Welford Road, LE1 5WW Leicester, UK.
[Walker, A Rosemary] Glenfield Hospital, Department of PathologyLeicester, UK.
[Muller, Salli] Glenfield Hospital, Department of PathologyLeicester, UK.
[Abrams, R Keith] University of Leicester, Department of EpidemiologyLeicester, UK.
[Steward, P William] Leicester Royal Infirmary, Department of Medical Oncology, Welford Road, LE1 5WW Leicester, UK.
[O’Byrne, J Kenneth] Leicester Royal Infirmary, Department of Medical Oncology, Welford Road, LE1 5WW Leicester, UK.
RP O’Byrne, JK (reprint author), Leicester Royal Infirmary, Department of Medical Oncology, LE1 5WW Leicester, UK.
EM ken.obyrne@lri.org.uk
CR Amstad PA, Lik H, Ichimiya M, et al: bcl-2 enhancement of malignant transformation in mouse epidermal JB-6 cells. Mol Carcinogenesis 20:231-239, 1997.
Anton RC, Brown RW, Younes M, et al: Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: Analysis of 427 cases. Hum Pathol 28:1079-1082, 1997.
Apolinario RM, van der Valk P, de Jong JS, et al: Prognostic value of the expression of p53, bcl-2, and baxoncoproteins, and neovascularization in patients with radically resected nonsmall- cell lung cancer. J Clin Oncol 15:2456-2466, 1997.
Dobbs SP, Brown LJR, Ireland D, et al: Bcl-2, platelet-derived growth factor, PD-ECGF), vascular endothelial growth factor, VEGF), and angiogenesis in cervical intraepithelial neoplasia, CIN, and squamous cell carcinoma, SCC). Br J Cancer 78:S1,49, 1998.
Evan GI, Wyllie AH, Gilbert CS, et al: Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119-128,1992.
Fleming MV, Guinee DG, Chu WS, et al: Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients. Human Pathol 29:60-64, 1998.
Fontanini G, Boldrini L, Vignati S, et al: Bcl-2 and p53 regulate vascular endothelial growth factor, VEGF)-mediated angiogenesis in non-small cell lung carcinoma. Eur J Cancer 34:718- 723, 1998.
Kobayashi N, Ishii M, Ueno Y, et al: Co-expression of Bcl-2 protein and vascular endothelial growth factor in hepatocellular carcinomas treated by chemoembolization. Liver 19:25-31, 1999.
Koukourakis MI, Giatromanolaki A, O’Byrne KJ, et al: Potential role of bcl-2 as a suppressor of tumor angiogenesis in nonsmall cell lung cancer. Int J Cancer 74:565-570, 1997.
Lotem J, Sachs L: Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and defective myeloid leukaemia cells. Cell Growth Different 4:41- 47, 1993.
Minn AJ, Swain RE, Ma A, et al: Recent progress on the regulation of apoptosis by Bcl-2 family members. Advances in Immunology 70:245-279, 1998.
Miyashita T, Reed JC: Bcl-2 gene transfer increases relative resistance of S49.1 and WEH17.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic regimes. Cancer Res 52:5407-5411, 1992.
Mountain CF: Revisions in the international system for staging lung cancer. Chest 111:1711-1717, 1997.
Naumovski L, Cleary ML: The p53-binding protein 53BP2 also interacts with Bcl-2 and impedes cell cycle progression at G2/M. Mol Cell Biol 16:3884-3892, 1996.
Nunez G, London L, Hockenberry D, et al: Deregulated bcl-2 gene expression selectively prolongs survival of growth factordeprived haemopoeitic cell lines. J Immunol 144:3602-3610, 1990.
Ohsaki Y, Toyoshima E, Fujiuchi S, et al: bcl-2 and p53 protein expression in non-small cell lung cancers: correlation with survival time. Clin Cancer Res 2:915-920, 1996.
O’Neill AJ, Staunton MJ, Gaffney EF: Apoptosis ocurs independently of bcl-2 and p53 over-expression in non-small cell lung cancer. Histopathology 29:45-50, 1996.
Pezzella F, Turley I, Kuzu I, et al: Bcl-2 protein in non-small cell lung carcinoma. N Eng J Med 329:690-694, 1993.
Ryan JJ, Prochownik E, Gottlieb CA, et al: C-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. Proc Natl Acad Sci USA 91:5878-5882, 1994.
Saegusa M, Takano Y, Hashimura M, et al: The possible role of bcl-2 expression in the progression of tumors of the uterine cervix. Cancer 76:2297-2303, 1995.
Silvestrini R, Benini E, Veneroni S, et al: p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients. J Clin Oncol 14:1604-1610, 1996.
Walker C, Robertson L, Myskow M, et al: Expression of the Bcl- 2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer 72:164-169, 1995.
World Health Organisation: The World Health Organisation histological typing of lung cancer. Am J Clin Pathol 77:123- 136, 1982.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 87
EP 92
PG 6
ER
PT J
AU Croce, VM
Price, RM
Segal-Eiras, A
AF Croce, V Maria
Price, R Mike
Segal-Eiras, Amada
TI Detection and Isolation of MUC1 Mucin from Larynx Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE laryngeal carcinoma; tumor antigens; MUC1mucin
ID laryngeal carcinoma; tumor antigens; MUC1mucin
AB The progression from uncontrolled cell proliferation to invasion and metastasis of epithelial tumors is partially understood. Alteration of epithelial mucin expression have been described in different malignant localizations but only few attempts have been made to identify mucin expression in malignant laryngeal tumors. In the present report, results are shown of studies on the expression of mucins and carbohydrate related antigens in laryngeal cancer and on the isolation of MUC1 mucin from this tumor tissue. Malignant laryngeal specimens were processed for immunohistochemical analysis and for extranuclear membrane fractions (ENM) which were obtained by ultracentrifugation. Subsequently, ENM samples were centrifuged in density-gradient; the analysis of fractions was performed by means of SDS-PAGE and Western-blotting. The panel of monoclonal antibodies (MAbs) included anti MUC1 mucin, anti Lewis x, anti sialyl Lewis x, anti Lewis y, anti MUC-5B, anti oral mucin (gp230), anti Tn hapten, anti p53 and anti cytokeratins. By immunohistochemistry, it was possible to detect MUC1 mucin, Lewis x and Lewis y showing strong reactions while sialyl-Lewis x and Tn antigen only reacted weakly in a few cells; cytokeratins were detected in all samples. In ENM derived fractions obtained by CsCl centrifugation, MUC1 was demonstrated by Western blotting. Conclusions: (1) laryngeal cancer antigenic expression comprises mostly MUC1 mucin, Lewis x, Lewis y as well as Tn antigen and (2) the methodology here employed is useful to isolate MUC1 from tumor samples.
C1 [Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Price, R Mike] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research LaboratoriesNottingham, UK.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM as-eiras@netverk.com.ar
CR Aksoy N, Corfield AP, Paraskeva C, et al: Human intestinal mucin MUC2 in in vitro two adenoma-carcinoma sequences originated from a single benign colonic adenoma cell line: In vitro evidence for the neotransformation. 5th International Workshop on Carcinoma Associated Mucins, Cambridge, UK, 1998.
Barnd DL, Lan M, Metzgar R, et al: Specific, MHC-unrestricted recognition of tumor associated mucins by human cytotoxic T cells. Proc Natl Acad Sci USA; 86:7159-7163, 1989.
Bradford CR: Predictive factors in head and neck cancer. Hemotol Oncol Clin North Am 13:777-785, 1999.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 93
EP 99
PG 7
ER
PT J
AU Athanassiadou, P
Gonidi, M
Liossi, A
Petrakakou, E
Nakopoulou, Ly
Zerva, Ch
Athanassiades, P
AF Athanassiadou, Pauline
Gonidi, Maria
Liossi, Anna
Petrakakou, Efthalia
Nakopoulou, Lydia
Zerva, Cherry
Athanassiades, Peter
TI Moc-31, Fibronectin and CEA in the Differential Diagnosis of Malignant Effusions: An Immunocytochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MOC-31; CEA; fibronectin; immunocytochemistry; effusions; reactive atypical mesothelial cells
ID MOC-31; CEA; fibronectin; immunocytochemistry; effusions; reactive atypical mesothelial cells
AB In discriminating benign and malignant origins of cytologically suspicious effusion smears a panel of antibodies against carcinoembryonic antigen (CEA), Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One hundred and thirty seven effusions were studied of which 107 had a malignant and 30 a benign aetiology as determined by clinical and histological examination. Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious. Staining for F was positive in all effusions of benign and 3 of malignant origin. MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of benign origin. Positive CEA was observed in 43% of effusions of malignant origin and in 10 of benign origin. The combination of MOC-31 positivity measured the sensitivity and specificity of the cytological examination in cases where the cytological examination result was suspicious as did F positivity improve the sensitivity for a benign origin of the effusion. Positivity or negativity for CEA is less valuable than the other parameters.
C1 [Athanassiadou, Pauline] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Gonidi, Maria] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Liossi, Anna] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Petrakakou, Efthalia] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Nakopoulou, Lydia] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Zerva, Cherry] University of Athens, Cytology Department, Pathology Laboratory, 75 M.Asias Str., GR-115 27 Athens, Greece.
[Athanassiades, Peter] University of Athens, Alexandra Hospital, Clinical TherapeuticsAthens, Greece.
RP Athanassiadou, P (reprint author), University of Athens, Cytology Department, Pathology Laboratory, GR-115 27 Athens, Greece.
CR Bedrossian CWM: Malignant effusions: A multimodal approach to cytologic diagnosis. New York, Igaku-Shoin Medical Publishers, 1994.
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Kyrkou K, Iatridis S, Athanassiadou P, et al: The cytologic application of carcinoembryonic antigen for the discrimination of malignant from benign serous effusions. Cancer Det Prev 8:247-54, 1985.
Lee JS, Nam JH, Lee MC et al: Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in serous effusions. Acta Cytol 40:631-636, 1996.
Mafisso AA, Carder PJ: Monoclonal antibodies in the cytodiagnosis of serous effusions. Cytopathology 1:119-28, 1990.
Mezger J, Stotzer O, Schilli G et al: Identification of carcinoma cells in ascitic and pleural fluid: Comparison of four panepithelial antigens with carcinoembryonic antigen. Acta Cytol 36:75- 81, 1992.
Naylor B. Pleural, peritoneal and pericardial fluids. In: Bibbo M, ed. Comprehensive Cytopathology. Philadelphia: Saunders Co; 1991, 541-614.
Ordonez NG, Mackay B: The roles of immunohistochemistry and electron microscopy in distinguishing epithelial mesothelioma of the pleura from adenocarcinoma. Adv Anat Pathol 3:273-93, 1996.
Ordonez NG: Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The MD Anderson experience and a critical review of the literature. Am J Clin Pathol 109:85-89, 1998.
Ruitenbeek T, Gouw A, Poppema S: Immunocytology of body cavity fluids. MOC-31, a monoclonal antibody discriminating between mesothelial and epithelial cells. Arch Pathol Lab Med 118:265-269, 1994.
Sehested M, Ralfkieaer E, Rasmussen J: Immunoperoxidase demonstration of carcinoembryonic antigen in pleural and peritoneal effusions. Acta Cytol 27:124-27, 1983.
Souhami RL, Beverley PCL, Bobrow LG, et al: Antigens of lung cancer results of the Second International Workshop on Lung Cancer Antigens. J Natl Cancer Inst 3:609-12, 1991.
Wirth PR, Legier J, Wright GL: Immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma. Cancer 67:655-62, 1991.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 100
EP 103
PG 4
ER
PT J
AU Salehnia, M
Farzad, RT
Tachikhani, M
Torghaban, ShSh
Al-Traihi, T
AF Salehnia, Mogdeh
Farzad, R Tahereh
Tachikhani, Mohamad
Torghaban, Sh Shams
Al-Traihi, Taki
TI Alkaline Phosphatase Histochemistry and Biochemistry in the Diagnosis of Complete Hydatidiform Mole
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE alkaline phosphatase; placental alkaline phosphatase; complete hydatidiform mole; gestational trophoblastic disease
ID alkaline phosphatase; placental alkaline phosphatase; complete hydatidiform mole; gestational trophoblastic disease
AB The purpose of this study was a complementary method to the diagnosis and prognosis of complete hydatidiform mole (CHM) and differentiate it from the other cases of gestational trophoblatic diseases. This was done by examining the quality and quantity of the total and the placental alkaline phosphatase activity. The ALP in the tissues and sera from 12 patients were compared with 13 control normal non-pregnant and 30 control pregnant females. The enzyme activities were determined by biochemical and histochemical examination.The placental tissues were obtained from uterine curettage, or after delivery which then were frozen in a liquid nitrogen and processed for biochemical study. Cryosections were histochemically stained for ALP and PLAP by the azo coupling method. Isoenzyme specificity was evaluated by heating the tissue at 65°C for 15 min while the including L-phenylalanine (50 mM), D-phenylalanine (50 mM) and L-homoarginine (50 mM) were used for chemical inhibition study. The activity of ALP and PLAP of patients were reduced in comparison with pregnant control group (P<0.05). There was no significant difference between the patients and non-pregnant control (P<0.05) group. The localization of enzyme activities in cryosections of all groups were in the basal, apical, and the cytoplasm of syncytiotrophoblast cells. The ALP in all the groups was thermostable (65°C for 15 min) and was inhibited by L-phenylalanine, but no inhibition was seen with L – homoarginine in patients group only. These findings suggest that the PLAP is a useful marker in the diagnosis and prognosis of hydatidiform mole.
C1 [Salehnia, Mogdeh] School of Medical Sciences, Tarbiat Modarres University, Department of HistologyTehran, Iran.
[Farzad, R Tahereh] School of Medical Sciences, Tarbiat Modarres University, Department of HistologyTehran, Iran.
[Tachikhani, Mohamad] School of Medical Sciences, Tarbiat Modarres University, Department of HistologyTehran, Iran.
[Torghaban, Sh Shams] School of Medical Sciences, Tarbiat Modarres University, Department of HistologyTehran, Iran.
[Al-Traihi, Taki] School of Medical Sciences, Tarbiat Modarres University, Department of HistologyTehran, Iran.
RP Salehnia, M (reprint author), School of Medical Sciences, Tarbiat Modarres University, Department of Histology, Tehran, Iran.
CR Beckstead JH: Alkaline phosphatase histochemistry in human germ cell neoplasms. AM J Surg Pathol 7:341-349, 1983.
Bracken MB: Incidence and aetiology of hydatidiform mole: an epidemiological review. Br J Obstet Gynaecol 94:1123-1135, 1987.
Buckley JD: The epidemiology of molar pregnancy and choriocarinoma. Clin Obstet Gynecol 27:153, 1984.
Bur GE, Hertig AT, F.A.C.O.G, et al: Histochemical aspects of hydatidiform mole and choriocarcinoma. Obstet Gynecol 19:156-181, 1962.
Byers DA, Fernley HN, Walker PG: Studies on alkaline phosphatase inhibition of human placental phosphoryl phosphatase by L – phenyl alanine. Eur J Biochem 29:197-204, 1972.
Cadeau MJ, Malkin A: Relative heat stability for the identification of serum alkaline phosphatase isoenzymes. Clin Chim Acta 45:235-242, 1973.
Chase JS, Check JH, Nowroozi KH, Wu CH: First trimester serum levels of the -subunit of human chorionic gonadotropin in a tubal molar pregnancy. Am J Obstet Gynecol 157:910, 1987.
Cheah PL, Looi LM. Expression of placental proteins in complete and partial hydatidiform moles. Pathol 26: 115-118, 1994.
Check JH., Nowroozi KH., Chase JS, et al. False – positive human chorionic gonadotropin levels caused by a heterophile antibody with the immunoradiometric assay. Am J Obstet Gynecol 158: 99-100, 1988.
Danihel L, Porubsky J, Vojtassak J, et al: Trophoblastic disease I. Use of imunohistochemistry in the diagnosis of complete hydatidiform moles. Cesk patol 30:76-79, 1994.
Danihel L, Porubsky J, Vojtassak J, et al: Trophoblastic disease II. Immunohistochemical and cytogenetic parameters of partial hydatidiform moles. Cesk Patol 30:80-84, 1994.
Fukunaga M, Migazawa Y, Sugisbita M, et al: Immunohistochemistry of molar and non-molar placentas with special reference to their differenial diagnosis. Acta Pathol Jpn 43:683-689, 1993.
Grimes DA: Epidemiology of gestational trophoblastic disease. Am J Obstet Gynecol 150:309-318, 1984.
Ilancheran A, Singh P, Sen DK, et al: Up date on chemotherapy of gestational trophoblastic disease. Singapore J Obstet Gynecol 19:53-60, 1988.
Kaldor G: Clinical enzymology New York: Prager publisher 87- 112, 1983.
Koid O, Iwai S, Kanno T, et al: Isoenzymes of alkaline phosphatase in germinoma cells. Am J Clin Pathol 89:611-616, 1988.
Lin CW, Fishman WH: L – homoarginine, an organospecific, uncompetitive inhibitor of human liver and bone alkaline phosphohydrolases. J Biol Chem 247:3082-3087, 1972.
Losch A, Kainz C: Immunohistochemistry in the diagnosis of the gestational trophoblatic disease. Acta Obstet Gynecol Scand 75:753-756, 1996.
Mckay DG, Hertig AT, Adams EC, et al: Histochemical observations on the germ cells of human embryos. Anat Rec 117: 201-219, 1953.
Mc Laughlin PJ, Gee H, Johnson PM: Placental – type alkaline phosphatase in pregnancy and malignancy plasma: specific estimation using a monoclonal antibody in a solid phase enzyme immunoassay. Clinica Chimica Acta 130:199-209, 1983.
Ming Chu T: Biochemical Markers for cancer. Clinical and biochemical analysis; 11, New York: Marcel Dekker, INC publisher 93-115, 1982.
Ozturk M, Berkowitz R, Goldstein O, et al. Differential production of human chorionic gonadotropin and free subunits in gestational trophoblastic disease . Am J Obstet Gynecol 158:193- 198, 1988.
Sabellek WM: Alkaline phosphatase, laboratory and clinical lmplications. J Chromato 429:419-444, 1988.
Smith DB, O Reilly SM, Newland FS: Current approaches to diagnosis and treatment of gestational trophoblastic disease. Curr Opin Obstet Gynecol 5:84-91, 1993.
Sonnenwright AC, Jarett L: Gradwohl’s Clinical laboratory methods and diagnosis. 8th ed London: C.V. Mosby Co. 256- 271, 1980.
Wang TH, Wag HS: Gestational trophoblastic diseases: Current trends and perspectives. J Formos Med Assoc 94: 449-457, 1995
Yusoff Dawood M, Facog, Saxena BB, et al: Human chorionic gonadotropin and its subunits in hydatidiform mole and choriocarcinoma. Obstet Gynecol 50:172-180, 1977.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 105
EP 110
PG 6
ER
PT J
AU Szabo, J
Hegedus, Gy
Bartok, K
Kerenyi, T
Vegh, A
Romics, I
Szende, B
AF Szabo, Janos
Hegedus, Gyorgy
Bartok, Katalin
Kerenyi, Tibor
Vegh, Attila
Romics, Imre
Szende, Bela
TI Improving Diagnostic Accuracy of Prostate Carcinoma by Systematic Random Map-biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE map-biopsy; prostate; carcinoma; RDE
ID map-biopsy; prostate; carcinoma; RDE
AB Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic ''map” biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.
C1 [Szabo, Janos] Central Military Hospital, Department of UrologyBudapest, Hungary.
[Hegedus, Gyorgy] Central Military Hospital, Department of UrologyBudapest, Hungary.
[Bartok, Katalin] Military Hospital, Department of PathologyBudapest, Hungary.
[Kerenyi, Tibor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Vegh, Attila] Central Military Hospital, Department of UrologyBudapest, Hungary.
[Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Resnick MI: Transrectal ultrasound guided versus digitally directed prostatic biopsy: A comparative study. J Urol 139:754- 757, 1988.
Hodge KK, McNeal JE, Stamey TA: Ultrasound guided transrectal core biopsies of the palpably abnormal prostate. J Urol 142:66-70, 1989.
Lippman HR, Ghiatas AA, Sarosdy MF: Systematic transrectal ultrasound guided prostate biopsy after negativ digitally directed prostate biopsy. J Urol 147:827-829, 1992.
Terris MK, McNeal JE, Stamey TA: Detection of clinically significant prostate cancer by transrectal ultrasound guided systematic biopsies. J Urol 148:829-832, 1992.
Irwin MB, Trapasso JG, Stamey TA: Identification of insignificant prostate cancers. Analysis of preoperative parameters. Urology 44:862-868, 1994.
Devonec M, Fendler JP, Monsallier M, et al: The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. J Urol 143:316-319, 1990.
Hodge KK, McNeal JE, Terris MK, et al: Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 142:71-75, 1989.
Hammerer P, Huland H, Cooner WH: Systematic sextant biopsies in 651 patients reffered for prostate evaluation. J Urol 151:99-104, 1994.
Vallancien G, Prapotnich D, Veillon B, et al: Systematic prostatic biopsies in 100 men with no suspicion of cancer on digital rectal examination. J Urol 146:1308-1312, 1991.
Gasman D, Abbou CC: Biopsies prostatiques: technique, interets et complitatious. Entretiens de Bichat Urologie. Abstract. 1995.
Jewett HJ: Significance of the palpable prostatique nodule. JAMA 160:838-839, 1956.
Lee F, Trop-Pedersen S, Littrup PJ, et al: Hypoechoic lesions of the prostate: clinical relevance of tumor size, digital rectal examination, and prostate specific antigen. Radiology 170:29- 32, 1989.
Holm HH, Gammelgaard J: Ultrasound guided precise needle placement in the prostate and seminal vesicles. J Urol 125:385- 387, 1981.
Cooner WH, Mosley BR, Rutherford Jr CL, et al: Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol 143:1146-1154, 1990.
Topr-Pedersen S, Lee F, Littrup PJ, et al: Transrectal biopsy of the prostage guided with transrectal US: Longitudinal and multiplanar scanning. Radiology 170:23-27, 1989.
Coplen DE, Andriole GL, Yuan JJJ, et al: The ablity of systematic transrectal ultrasound guided biopsy to detect prostate cancer in men with the clinical diagnosis of benign prostatic hyperplasia. J Urol 146:75-77, 1991.
Vashi AR, Wojno KJ, Henricks W, et al: Determination of the reflex range and appropriate cutpoints for percent free PSA prostate specific antigen in 413 men referred for prostatic evaluation using the AxSYM system. Urology 49:19-27, 1997.
William J, Catalona, et al: Evaluation of percentage of free serum prostatic specific antigen to improve specificity of prostate cancer screening. JAMA 274:1214-1220, 1995.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 111
EP 113
PG 3
ER
PT J
AU Perambakam, S
Naresh, K
Nerurkar, A
Nadkarni, J
AF Perambakam, Supriya
Naresh, N. Kikkeri
Nerurkar, Ashutosh
Nadkarni, Jayshree
TI Intra-tumoral Cytolytic Cells: Pattern of Distribution in B-cell Non Hodgkin’s Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lymphoma; T-cells; CD4; CD8; TIA-1; NK cells; tumor infiltrating lymphocytes; cytotoxic cells; B-cell
ID lymphoma; T-cells; CD4; CD8; TIA-1; NK cells; tumor infiltrating lymphocytes; cytotoxic cells; B-cell
AB Non-Hodgkin’s lymphomas (NHLs) constitute a heterogeneous group of lymphoid neoplasms and a majority of them in India are of B-cell phenotype. Varying numbers of T lymphocytes and natural killer (NK) cells are consistently present within the lymph nodes (LNs). The role of these ''reactive'' cells is becoming understood. TIA-1 is a cytotoxic granule associated RNA binding protein, the expression of which is restricted to cytotoxic T lymphocytes (CTLs) and NK cells. Snap frozen lymph node biopsies obtained from 41 B-cell NHLs were localized for intra-tumoral TIA-1 + cytolytic cells by immunohistochemistry. Distribution of T cell subsets and NK cells were also quantified. Cells expressing TIA-1 antigen was observed in all the cases, seen as a strong granular cytoplasmic signal. Results indicate significantly higher number of TIA-1 cytolytic cells outside (periphery of the follicle and interfollicular areas) than within the neoplastic follicle in follicular lymphomas (p<0.001). In small lymphocytic lymphomas, cytolytic cells were mainly seen as uniformly scattered single cells, distributed throughout the tumor environment. In mantle cell and diffuse large B-cell lymphomas these were most often seen as small clusters and less frequently as singly scattered cells. Higher numbers of CD4 + than the CD8 + T cells were observed in most cases. Contrary to the follicles in follicular hyperplasia, CD57 + NK cells were predominantly observed outside the neoplastic follicle in follicular lymphomas (FLs). These results outline specific interactions between the potential anti-tumoral cytolytic and the malignant cells of B-cell NHLs.
C1 [Perambakam, Supriya] Tata Memorial Centre, Cancer Research Institute, 400 012 Parel, Mumbai, India.
[Naresh, N. Kikkeri] Tata Memorial HospitalParel, Mumbai, India.
[Nerurkar, Ashutosh] Tata Memorial HospitalParel, Mumbai, India.
[Nadkarni, Jayshree] Tata Memorial Centre, Cancer Research Institute, 400 012 Parel, Mumbai, India.
RP Nadkarni, J (reprint author), Tata Memorial Centre, Cancer Research Institute, 400 012 Parel, India.
EM cri3@soochak.ncst.ernet.in
CR Anderson P, Nagler-Anderson C, O’Brien C, et al: A monoclonal antibody reactive with a 15-kDa cytoplasmic granuleassociated protein defines a subpopulation of CD8+ T lymphocytes. J Immunol 144:574-582, 1990.
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Harcis NL, Bhan A: Distribution of T cell subsets in follicular and diffuse lymphomas of B cell type, Am J Pathol 113:172- 180,1983.
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Tian Q, Streuli M, Saito H, et al: A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell 67: 629-639, 1991.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 114
EP 117
PG 4
ER
PT J
AU Oz, B
Karayel, AF
Gazio, LN
Ozlen, F
Balci, K
AF Oz, Buge
Karayel, Anik Ferah
Gazio, LU Nurperi
Ozlen, Fatma
Balci, Kerem
TI The Distribution of Extracellular Matrix Proteins and CD44S Expression in Human Astrocytomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE astrocytic tumors; extracellular matrix proteins; CD44; tenascin; immunohistochemistry; anaplastic astrocytoma; glioblastoma
ID astrocytic tumors; extracellular matrix proteins; CD44; tenascin; immunohistochemistry; anaplastic astrocytoma; glioblastoma
AB Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.
C1 [Oz, Buge] Istanbul Medical Faculty, Department of Pathology, Aksaray, 34304 Istanbul, Turkey.
[Karayel, Anik Ferah] Istanbul Medical Faculty, Department of Pathology, Aksaray, 34304 Istanbul, Turkey.
[Gazio, LU Nurperi] Istanbul University, Cerrahpaºa Medical Faculty, Department of NeurosurgeryIstanbul, Turkey.
[Ozlen, Fatma] Istanbul University, Cerrahpaºa Medical Faculty, Department of NeurosurgeryIstanbul, Turkey.
[Balci, Kerem] Istanbul Medical Faculty, Department of Pathology, Aksaray, 34304 Istanbul, Turkey.
RP Oz, B (reprint author), Istanbul Medical Faculty, Department of Pathology, 34304 Istanbul, Turkey.
EM ferhanoz@tkbbv.org.tr
CR Ariza A, Lopez D, Mate JL et al: Role of CD44 in Invasiveness of Glioblastoma Multiforme and the Noninvasivness of Meningioma. Hum Pathol 26:1144-1147, 1995.
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Brodkey JA, Laywell FD, O’Brien TF, et al: Focal Brain Injury and Upregulation of a Developmentally Regulated Extracellular Matrix Protein. J Neurosurg 82:106-112, 1995.
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Fasana M, Sabatini MT, Wieczorek R, et al: CD44 and Its v6 Spliced Variant in Lung Tumors. Cancer 80:34-41, 1997.
Fox SB, Fawcett J, Jackson DG, et al: Normal Human Tissues, in Addition to some Tumors, Express Multiple Different CD44 Isoforms. Cancer Res 54:4539-4546, 1994.
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Iczkowski KA, Shanks JH, Bostwick DG: Loss of CD44 Variant 6 Expression Differentiates Small Cell Carcinoma of Urinary Bladder from Urothelial, transitional cell, Carcinomas. Histopathol 32:322-327, 1998.
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Khoshyomn S, Penar PL, Wadsworth MP, et al: Localization of Cd44 at the Invasive Margin of Glioblastomas by Immunelectron Microscopy. Ultrastruct Pathol 21:517-425, 1997.
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Koukoulis GK, Gould VE, Bhattacharyya A, et al: Tenascin in Normal, Reactive, Hyperplastic and Neoplastic Tissues. Hum Pathol 22:636-643, 1997.
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Lagorge-Pages C, Paraf F, Dubuis S, et al: Expression of CD44 In Premalignant and Malignant Barret’s Oesephagus. Histopathol 37:7-14, 1998.
Lesley J, Hyman R, Kincade PW: Cd44 and its Interaction with Extracellular Matrix. Adv Immunol 54:271-335, 1993.
Li H, Hamou MF, Tribolet N, et al: Variant CD44 Adhesion Molecules are Expressed in Human Brain Metastases but not in Glioblastomas. Cancer Res 53:5345-5349, 1993.
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Maenpa A, Kovanen PE, Paetau A, et al: Lymphocyte Adhesion Molecule Ligands and Extracellular Matrix Proteins in Gliomas and Normal Brain: Expression of VCAM-1 in Gliomas. Acta Neuropathol, Berl, 94:216-225, 1997.
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Penno MB, August JT, Baylin SB, et al: Expression of CD44 in Human Lung Tumors. Cancer Res 54:1381-1387, 1994.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 118
EP 124
PG 7
ER
PT J
AU Suda, K
Nobukawa, B
Yamasaki, Sh
Suzuki, F
Shimizu, H
Takase, M
AF Suda, Koichi
Nobukawa, Bunsei
Yamasaki, Shigetaka
Suzuki, Fujihiko
Shimizu, Hideo
Takase, Masaru
TI Pre-existing Histological Type and Developmental Mechanism of Mucinous Noncystic Carcinoma of Pancreas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pancreas cc; intraductal papillary-mucinous cc; ductal adenocc; mucin overproduction; mucinous degeneration; MUC immunoreactivity
ID pancreas cc; intraductal papillary-mucinous cc; ductal adenocc; mucin overproduction; mucinous degeneration; MUC immunoreactivity
AB Eleven cases with mucinous noncystic carcinoma (MC) of the pancreas were studied by histology and mucin immunohistochemistry, to elucidate the mechanism, or route of development, and pre-existing histological type of MC of the pancreas. These MCs were observed in close approximation to, or surrounding, intraductal papillary-mucinous carcinomas (IPMCs), and were centrally situated among ductal adenocarcinomas (DAs). Hence, the 11 cases originated from 8 IPMCs and 3 DAs. The mechanism and routes to MC were divided into four types as follows: IPMC directly invaded the stroma (4 cases), over-production of mucin in IPMC expanded the branches of the pancreatic duct possibly resulting in rupture (3 cases), DA underwent extreme mucinous degeneration (3 cases), and a recurrent form, as MC, at the surgical stump of IPMC (one case). The outcomes of MC cases with IPMC had variable survival rates, while those from DA had short durations. MUC immunoreactivity in MC was divided into three categories; anti-MUC1-positive only (2 IPMCs, 2 DAs), mixed anti-MUC1 and anti-MUC2-positive (3 IPMCs, one DA) and anti-MUC-positive only (3 IPMCs). Pre-existing MC histological types included both IPMC and DA. These two pre-existing types of MC involved mucin overproduction and mucinous degeneration. MUC immunoreactivity in MC revealed three patterns, which may be related to variable outcomes.
C1 [Suda, Koichi] Juntendo University School of Medicine, Department of Pathology, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan.
[Nobukawa, Bunsei] Juntendo University School of Medicine, Department of Pathology, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan.
[Yamasaki, Shigetaka] Juntendo University School of Medicine, Department of Pathology, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan.
[Suzuki, Fujihiko] Juntendo University School of Medicine, Department of Pathology, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan.
[Shimizu, Hideo] Juntendo University School of Medicine, Department of Pathology, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan.
[Takase, Masaru] Yamanashi Prefectural Central Hospital, Clinical Laboratory, Pathology DivisionYamanashi, Japan.
RP Suda, K (reprint author), Juntendo University School of Medicine, Department of Pathology, 113-8421 Tokyo, Japan.
EM ksuda@med.juntendo.ac.jp
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Ho SB, Niehans GA, Lyftogt C, et al: Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 53:641-651, 1993.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 125
EP 129
PG 5
ER
PT J
AU Ehrmann, J
Galuszkova, D
Ehrmann, J
Krc, I
Jezdinska, V
Vojtesek, B
Murray, GP
Kolao, Z
AF Ehrmann, Jioi
Galuszkova, Dana
Ehrmann, Jioi
Krc, Ivo
Jezdinska, Vera
Vojtesek, Booivoj
Murray, G Paul
Kolao, Zdenek
TI Apoptosis-related Proteins, BCL-2, BAX, FAS, FAS-L and PCNA in Liver Biopsies of Patients with Chronic Hepatitis B Virus Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; hepatitis B virus; FAS; FAS-L
ID apoptosis; hepatitis B virus; FAS; FAS-L
AB While the elimination of hepatitis B virus (HBV) is a common phenomenon at the end of the acute phase of disease, the persistence of HBV is characteristic for chronic hepatitis (CHB). Recent evidence indicates that the elimination of HBV is achieved by FAS/FAS-L induced apoptosis of infected hepatocytes. The aim of this study was to test the hypothesis that HBV persistence in the hepatocytes of CHB patients is due to the delayed onset of apoptosis caused by altered FAS/FAS-L interactions between lymphocytes and hepatocytes. The expression of FAS, FAS-L, BAX, BCL-2, ICE and PCNA in the liver biopsies of 55 patients (14 HBsAg positive, 20 patients with alcoholic hepatopathy, 21 patients with other hepatopathies) was tested by immunohistochemistry. Apoptosis of hepatocytes was evaluated by morphological as well as by TUNEL method. The results were correlated with a grading/staging score and analysed statistically using a one way analysis of variance and the Duncan test. Significantly highernumbers of BAX positive hepatocytes were observed in HBsAg positive patients when compared to control groups. Similarly, both BAX and FAS positive lymphocytes were more frequent in HBsAg positive patients. FAS-L positive lymphocytes and hepatocytes were numerous in all patient groups. Increased numbers of BAX positive hepatocytes in CHB may reflect the increased readiness of these cells to undergo apoptosis. However, the increased numbers of both BAX and FAS positive lymphocytes in CHB suggest that these cells may be particularly sensitive to FAS-L mediated apoptosis potentially resulting in lowered viability of these lymphocytes. This may explain, at least in part, the defective removal of virus-infected cells in chronic hepatitis. However, we cannot rule out the possibility that survival of hepatocytes during CHB may be due to other mechanisms such as defects in apoptosis activation triggered by CD40, defects involving DNase and/or other caspases downstream in the apoptotic cascade within these cells, or to defects in CTL function.
C1 [Ehrmann, Jioi] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnivotinska 3, CZ-77515 Olomouc, Czech Republic.
[Galuszkova, Dana] Faculty of Medicine, PalackyUniversity, Second Department of Internal MedicineOlomouc, Czech Republic.
[Ehrmann, Jioi] Faculty of Medicine, PalackyUniversity, Second Department of Internal MedicineOlomouc, Czech Republic.
[Krc, Ivo] Faculty of Medicine, PalackyUniversity, Second Department of Internal MedicineOlomouc, Czech Republic.
[Jezdinska, Vera] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnivotinska 3, CZ-77515 Olomouc, Czech Republic.
[Vojtesek, Booivoj] Masaryk Memorial HospitalBrno, Czech Republic.
[Murray, G Paul] School of Health Sciences, University of Wolverhampton, Division of Biomedical SciencesWolverhampton, UK.
[Kolao, Zdenek] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnivotinska 3, CZ-77515 Olomouc, Czech Republic.
RP Ehrmann, J (reprint author), Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, CZ-77515 Olomouc, Czech Republic.
EM erman@tunw.upol.cz
CR Adams JM, Cory S: The Bcl –2 protein family: arbiters of cell survival. Science 281:1322-26, 1998.
Afford SC, Randhawa S, Eliopoulos AG, et al: CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface fas ligand expression and amplifies fas-mediated hepatocyte death during allograft rejection. J Exp Med 189:441-6, 1999.
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Beutler B, van Huffel C: Unraveling function in the TNF ligand and receptor families. Science 264:667-668, 1994.
Dayan CM: FasL expression on epithelial cells: the Botazzo- Feldmann hypothesis revisited. Immunology Today 18:203, 1997.
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French LE, Tschopp J: Thyroiditis and hepatitis: FAS on the road to disease. Nature Medicine 3:387-388, 1997.
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Kroemer G: The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nature Medicine 3:614-620, 1997.
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Liu CC, Walsh CM, Young JDE: Perforin: structure and function. Immunol Today 16:194-201, 1995.
Luo KX, Zhu YF, Zhang LX, et al: In situ investigation of Fas/FasL expression in chronic hepatitis B infection and related liver diseases. J Viral Hepat 4:303-7, 1997.
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Marinos G, Torre F, Chokshi S, et al: Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: a major factor in activation of the host immune response to the hepatitis B virus. Hepatology 22:1040-1049, 1995.
Mochizuki K, Hayashi N, Hiramatsu N, et al: Fas antigen expression in liver tissues of patients with chronic hepatitis B. J Hepatology 24:1-7, 1996.
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Nakamoto Y, Guidotti LG, Pasquetto V, et al: Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice. J Immunol 158:5692-7, 1997.
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Patel T, Gores GJ, Kaufmann SH: The role of proteases during apoptosis. FASEB J 10:587-597, 1996.
Peters M: Actions of cytokines on the immune response and viral interactions: an overview. Hepatology 23:909-916, 1996.
Reed JC: Double identity for proteins of the Bcl-2 family. Nature 387:773-776, 1997.
Rehermann B, Lau D, Hoofnagle JH, et al: Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 7:1655-1665, 1996.
Romero R, Lavine JE: Cytokine inhibition of the hepatitis B virus core promoter. Hepatology 23:17-23, 1996.
Ryo K, Kamogawa Y, Ikeda I, et al: FAS and FAS ligand strongly expressed in liver of fulminant hepatitis patients. Hepatology 22: AASLD Abstracts: 230 A, 1995.
Shibata S, Kyuwa S, Lee S, Toyota Y, et al: Apoptosis induced in mouse hepatitis virus infected cells by a virus specific CD8+ cytotoxic lymphocyte clone. J Virol 68:7540-7545, 1994.
Schaff Z, Lotz G, Schulte-Herman R: Pathomorphological characteristic and pathogenesis of viral hepatitis. Pathology Oncology Research 2:132-143, 1996.
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Yoong KF, Afford SC, Randhawa S, et al: DH: Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion. Am J Pathol 154:693-703, 1999.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 130
EP 135
PG 6
ER
PT J
AU Sharma, ChM
Arora, R
Lakhtakia, R
Mahapatra, KA
Sarkar, Ch
AF Sharma, Chand Mehar
Arora, Rina
Lakhtakia, Ritu
Mahapatra, Kumar Ashok
Sarkar, Chitra
TI Ependymoma with Extensive Lipidization Mimicking Adipose Tissue: A Report of Five Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Ependymoma; adipocyte; metaplasia; lipomatous change; signet ring cell; intracranial tumor
ID Ependymoma; adipocyte; metaplasia; lipomatous change; signet ring cell; intracranial tumor
AB Lipomatous ependymoma is a recently described entity and only 3 cases of this variant have been reported in the literature. We report 5 cases of this rare variant of ependymoma. Patients’ age ranged from 4 years to 45 years and, interestingly, all of them were males. Two tumors were supratentorial in location, 2 in the fourth ventricle and 1 was intramedullary. Microscopically all of them showed the classical histology of ependymoma along with lipomatous differentiation. The lipomatous component was composed of cells with a large clear vacuole pushing the nucleus to the periphery and giving a signet ring cell appearance. This component demonstrated positivity for GFAP and S-100 protein thereby confirming its glial lineage. Three of the 5 tumors were high grade (WHO-grade III), had a high MIB-1 labelling index (MIB-1 LI) and showed recurrence on follow-up. However, 2 were low grade (WHO grade II) and patients are free of disease till the last follow up.
C1 [Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Arora, Rina] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Lakhtakia, Ritu] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Mahapatra, Kumar Ashok] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarch@medinst.ernet.in
CR Budka H: Intracranial lipomatous hamartomas, intracranial “lipomas”). Acta Neuropathol 28:205–222, 1974.
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Davis DG, Wilson D, Schmitz M, et al: Lipidized medulloblastoma in adults. Human Pathol 24:900-995, 1993.
Ellison DW, Zygmunt SC, Weller RO: Neurocytoma/Lipoma, neurolipocytoma, of the cerebellum. Neuropathol Appl Neurobiol 19:95-98, 1993.
Giangaspero F, Cenacchi G, Roncarfil F, et al. Medullocytoma, lipidized medulloblastoma). A cerebellar neoplasm of adults with favourable prognosis. Am J Surg Pathol 20:656-64, 1996.
Hirato H, Nakazato Y, Iizima M: An unusual variant of ependymoma with extensive tumor cell vacuolization. Acta Neuropathol 93:310-316, 1997.
Kepes JJ, Rubinstein LJ, Eng LF: Pleomorphic xanthastrocytoma: a distinctive meningocerebral glioma of young subjects with relatively favourable prognosis. Cancer 44:1839-1852, 1979.
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Roda JM, Gutierrez–Molina M: Multiple intraspinal low grade astrocytomas mixed with lipoma, astrolipoma, Case report. J Neurosurgery 82:891-894, 1995.
Ruchoux MM, Kepes JJ, Dhellemmes P, et al: Lipomatous differentiation in ependymomas. A report of three cases and comparison with similar changes reported in other central nervous system neoplasms of neuroectodermal origin. Am J Surg Pathol 22:338-346, 1998.
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Shuster D, Herrick M, Horoupian D: Two unusual cases of central neurocytoma: a concomitantly occurring under fourth ventricular PNET, b-mixed with lipoma. Brain Pathol 4:433, 1994.
Soylemezoglu F, Soffer D, Onol B, et al: Lipomatous medulloblastoma in adults. A distinct clinicopathological entity. Am J Surg Pathol 20:413-418, 1996.
Walter A, Dingermans KP, Weinstein HC, Troost D: Cerebellar astrocytoma with extensive lipidization mimicking adipose tissue. Acta Neuropathol 88: 485-489, 1994.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 136
EP 140
PG 5
ER
PT J
AU Elek, G
Minik, K
Pajor, L
Parlagi, Gy
Varga, I
Vetesi, F
Zombori, J
AF Elek, Gabor
Minik, Karoly
Pajor, Laszlo
Parlagi, Gyula
Varga, Istvan
Vetesi, Ferenc
Zombori, Janos
TI New Human Dirofilariosesin Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE parasite; zoonosis; mosquito transmitted; Dirofilaria repens; histology
ID parasite; zoonosis; mosquito transmitted; Dirofilaria repens; histology
AB About ten cases of filariosis have recently been recorded in the Hungarian medical literature, six of them caused by Dirofilaria repens. Dirofilaria repensis a mosquito-transmitted filaroid worm in the subcutaneous tissue of dogs and cats in the temperate areas of the Old World. It accidentally infects man, too, and can remain unidentified due to physicians , poor knowledge of the parasite. In the last two years six new Dirofilaria repensinfections have been found in various parts of the country: five localised dermally and one in the deep tissues. Two of the cases might have been acquired in Italy during summer travels. Four patients, however, have never been abroad, these cases must be considered autochtonous infections. The thickness of the multilayered cuticle of the worm, diameter of the body and the size, form and number of the longitudinal ridges on its surface are used in the histological diagnosis of the the parasite.
C1 [Elek, Gabor] Military Hospital, Department of Pathology, Podmaniczky u 111., H-1062 Budapest, Hungary.
[Minik, Karoly] County Hospital of Borsod-Abauj-ZemplenMiskolc, Hungary.
[Pajor, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Parlagi, Gyula] Municipal Hospital, Del-Pest, Department of PathologyBudapest, Hungary.
[Varga, Istvan] Szent Istvan University, Faculty of Veterinary Medicine, Department of Pathology and Forensic Veterinary MedicineBudapest, Hungary.
[Vetesi, Ferenc] Municipal Hospital, Hodmezovasarhely, Department of PathologyHodmezovasarhely, Hungary.
[Zombori, Janos] Veterinary University, Parasitological DepartmentBudapest, Hungary.
RP Elek, G (reprint author), Military Hospital, Department of Pathology, H-1062 Budapest, Hungary.
CR Ashford RW, Dowse JA, Rogers WN, et al: Dirofilariasis of the breast. The Lancet, I:1198, 1989.
Avdiukhina TI, Supriaga VG, Postnova WN: Dirofilariasis in the countries of the CIS 1915-1996. Medsk Parazitol, Russia, 4:3-7, 1997.
Bardach H, Heimbucher J, Raff M: Subkutane Dirofilaria, Nochtiella, repens-Infection beim Menschen – Erste Fallbeschreibung in Osterreich und Ubersicht der Literatur. Wien Klin Wschr 93:123-127, 1981.
Boreham PFL, Atwell RB: Dirofilariasis. CRC Press, Boca Raton, Florida, 1988.
Gutierrez Y: Diagnostic features of zoonotic filariae in tissue sections. Human Pathology 15:514-525, 1984.
Kotlan A:On a new case of human filariidosis in Hungary. Acta Vet Acad Sci Hung 1:69-79, 1951.
Nemeth B, Kugler S: Ophthalmo-filariasis. Orvosi Hetilap 109: 195-197, 1968.
Pampiglione S, Elek G, Palfi P, et al: Human Dirofilaria repens infection in Hungary: a case in the spermatic cord and a review of the literature. Acta Vet Acad Sci Hung 47:77-83, 1999/a.
Pampiglione S, Rivasi F, Canestri Trotti G: Pitfalls and difficulties in histological diagnosis of Human Dirofilariasis due to Dirofilaria, Nochtiella, repens. Diagn Microbiol Infect Dis 34:57-64, 1999/b.
Pampiglione S, Bortoletti G, Fossarello M, et al: Dirofilariasi umana in Sardegna: 4 nuovi casi. Pathologica 88:472-477, 1996/a.
Pampiglione S, Brollo A, Ciancia EM, et al: Dirofilariasi umana sottocutanea, 8 ulteriori casi in Italia. Pathologica 88:91-96, 1996/c.
Pampiglione S, Canestri Trotti G, Rivasi F, et al: Human dirofilariasis in Greece: a review of reported cases and a description of a new, subcutaneous case. Ann Trop Med Parasitol 90:319- 328, 1996/b.
Pampiglione S, Rivasi F, Paolino S: Human pulmonary dirofilariasis. Histopathology 29:69-72, 1996/d.
Pampiglione S, Azzaro S, Bongiorno A, et al: La dirofilariosi oculare umana in Italia: descrizione di 6 nuovi casi. Revisione della casistica Italiana. Annali di Ottalmologia e Clinica Oculista. 121:257-277, 1995.
Pampiglione S, Arlotta MR, Ambrosio ED, et al: La dirofilariasi umana nel sud d’Italia. I. Regione Puglia. Pathologica 86:528-532, 1994.
Pampiglione S, Fruttaldo L, Mongio F, et al: Due casi clinici di filariasi zoonotica da probabile Dirofilaria repens. Pathologica 85:521-524, 1993.
Parlagi Gy, Sumi A, Elek G, et al: Szemuregi dirofilariosis. Magyar Szemeszet, In press, 2000., in Hungarian only)
Portnoy LG: Dirofilariasis. In: Pathology of infectious diseases., Eds: Conor DH, Chandler FW, Schwartz DA et al, Appleton and Lange, 1997, vol 2, pp1391-1396.
Settnes OP, Engebjerg E: Human subcutaneous dirofilariasis caused by Dirofilaria repens. Apmis 99:364-370, 1991.
Szell Z, Sreter T, Csikos K, et al: Autochton Dirofilaria repens fertozottseg kutyakban. Magy Ao Lapja 121:100-104, 1999., in Hungarian only)
Zahler M, Glaser B, Gothe R: Eingeschleppte Parasiten bei Hunden: Dirofilaria repens und Dipetalonema reconditum. Tierarztl Prax 25:388-392 1997.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 141
EP 145
PG 5
ER
PT J
AU Rieker, JR
Quentmeier, A
Weiss, C
Kretzschmar, U
Amann, K
Mechtersheimer, G
Blaker, H
Herwart, FO
AF Rieker, J Ralf
Quentmeier, Armin
Weiss, Carsten
Kretzschmar, Ulrich
Amann, Kerstin
Mechtersheimer, Gunhild
Blaker, Hendrik
Herwart, F Otto
TI Cystic Lymphangioma of the Small-Bowel Mesentery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE lymphangioma; small-bowel mesentery; infection; etiology; differential diagnosis
ID lymphangioma; small-bowel mesentery; infection; etiology; differential diagnosis
AB Cystic lymphangioma of the small-bowel mesentery is a rare manifestation of an intraabdominal tumor in elderly patients. We present a case of a small-bowel mesentery lymphangioma, causing fever and chills and present clinical and pathologic features. Furthermore, etiology and differential diagnosis of this tumor are discussed.
C1 [Rieker, J Ralf] University of Heidelberg, Department of Pathology, Pathologisches Institut, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Quentmeier, Armin] St. Josephskrankenhaus, Department of Surgery and RadiologyHeidelberg, Germany.
[Weiss, Carsten] St. Josephskrankenhaus, Department of Surgery and RadiologyHeidelberg, Germany.
[Kretzschmar, Ulrich] St. Josephskrankenhaus, Department of Surgery and RadiologyHeidelberg, Germany.
[Amann, Kerstin] University of Heidelberg, Department of Pathology, Pathologisches Institut, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Mechtersheimer, Gunhild] University of Heidelberg, Department of Pathology, Pathologisches Institut, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Blaker, Hendrik] University of Heidelberg, Department of Pathology, Pathologisches Institut, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Pathologisches Institut, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
RP Rieker, JR (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM ralf_rieker@med.uni-heidelberg.de
CR Barquist ES, Apple SK, Jensen DM, et al: Jejunal lymphangioma. An unusual cause of chronic gastrointestinal bleeding. Dig Dis Sci 42:1179-1183, 1997.
Bill AH, Sumner DS: A unified concept of lymphangioma and cystic hygroma. Surg Gynaecol Obstet 120:79, 1965.
Campbell WJ, Irwin ST, Biggart JD: Benign lymphangioma of the jejunal mesentery: an unusual cause of small bowel obstruction. Gut 32:1568, 1991.
Chodak P, Hurwitz A: Lymphangiectasis of stomach simulating polypoid neoplasm. Arch Intern Med 113:225-229, 1964.
Daniel S, Lazarevic B, Attia A:Lymphangioma of the mesentery of the jejunum: report of a case and a brief review of the literature. Am J Gastroenterol 78:726-729, 1983.
Dowed CN. Hygroma cysticum colli. Its structure and etiology. Ann Surg 58:112-132,1913.
Godart S: Embryological significance of lymphangiomas. Arch Dis Child 41:204-206, 1966.
Greene EI, Kirshenn MM, Greene JM: Lymphangioma of the transverse colon. Am J Surg 103:225-229, 1964.
Hanagiri T, Baba M, Shimabukuro T, et al: Lymphangioma in the small intestine: report of a case and review of the Japanese literature. Surg Today 22:363-367, 1992.
Hardin WJ, Hardy JD: Mesenteric cysts. Am Surg 26:42-49, 1960.
Kindblom LG, Angervall L: Tumors of lymph vessels. Contemp Issues Surg Pathol 18:163, 1991.
Kok KY, Mathew VV, Yapp SK: Lymphangioma of the smallbowel mesentery: unusual cause of intestinal obstruction. J Clin Gastroenterol 24:186-187, 1997.
Enzinger FM, Weiss SW: Tumors of the lymph vessels. In: Soft tissue tumors., Eds.: Enzinger FM, Weiss SW, Mosby , 1994, pp. 679-700.
Nakagawara G, Kojima Y, Mai M, et al: Lymphangioma of the transverse colon treated by transendoscopic polyectomy. Dis Colon Rectum 24:291-295, 1981.
Singh S, Maghrabi M: Small bowel obstruction caused by recurrent cystic lymphangioma. Br J Surg 80:1012, 1993.
Takiff H, Calabria R, Yin L, et al: Mesenteric cysts and intraabdominal cystic lymphangiomas Arch Surg 120:1266-1269, 1985.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 146
EP 148
PG 3
ER
PT J
AU Nash, RJ
AF Nash, RG John
TI Pathology in the New Medical Curriculum: What has replaced the Subject Courses?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE problem-based learning; pathology; medical education
ID problem-based learning; pathology; medical education
AB In line with the UK General Medical Council recommendations, the traditional, taught curriculum at Liverpool was replaced from 1996 by a new one using problem-based learning (PBL) as its principal method of information transfer. There is integration of clinical and preclinical studies, coupled with a reduction in the factual knowledge content and the disappearance of identifiable separate subject courses. Learning is now student-centred. This requires a new approach to the acquisition of pathology knowledge. 1. Pathology is included in all relevant PBL case scenarios by pathology representation on module planning and review committees. 2. Special study modules (SSMs) allow students to observe the practice of pathology including surgical and autopsy work, carry out a detailed study and write a dissertation. Career selectives are provided for individual students in the final year. 3. Clinicopathological (CPC) teaching meetings are held, with the discussion of case examples, clinicians and students contributing. 4. Assessments include the input of appropriate pathology content, integrated with other subjects. 5. A pathology teaching website is provided, containing images, notes, self-assessment questions, handouts, timetables and information. Although the 1996 intake have not yet completed their studies, the results of in-course assessments have been encouraging. The response to the pathology SSMs has been very positive, and the level of presentations and dissertations reached is of a high standard. With the disappearance of a separate subject course in pathology, the subject is being learned by other routes, and the students will complete their undergraduate course with a sound basis for proceeding with their further studies.
C1 [Nash, RG John] University of Liverpool, Department of Pathology, Duncan Building, Daulby Street, L69 3GA Liverpool, UK.
RP Nash, RJ (reprint author), University of Liverpool, Department of Pathology, L69 3GA Liverpool, UK.
EM jnash@liv.ac.uk
CR Bligh JA: Problem based, small group learning. BMJ, Editorial, 311:342-343, 1995.
Branda LA: Implementing problem-based learning. J Dental Education 54:548-549, 1990.
Catto G: Specialist registrar training., Editorial). BMJ 320:817- 818, 2000.
Ferrier BM: Problem-based learning: does it make a difference? J Dental Education 54:550-551, 1990.
General Medical Council. ‘Tomorrow’s Doctors’ London, Kiek and Reid,1993. Also on GMC website: www.gmc.org.uk
Neame R, Murphy B, Stitt F, Rake M: The impact of informatics. Universities without walls: evolving paradigms in medical education. BMJ 319:1296, 1999.
Neufeld VR, Barrows HS: The ‘McMaster philosophy’: an approach to medical education. J Medical Education 49:1040- 1050, 1974.
Pallie W, Carr DH: The McMaster medical education philosophy in theory, practice and histprical perspective. Medical Teacher 9:59-71, 1987.
Shaughnessy AF, Slawson DC: Are we providing doctors with the training and tools for lifelong learning? BMJ 319:1280, 1999.
Spencer JA, Jordan RK: Learner centred approaches in medical education. BMJ 318:1280-1283, 1999.
Towle A: Continuing medical education: changes in health care and continuing medical education for the 21st century. BMJ 316:301-304, 1999.
Walton HJ, Matthews MB: Essentials of problem-based learning. Medical Education 23:542-558, 1989.
Woodward CA: The effects of innovations in medical education at McMaster: a report on follow-up studies. Meducs 2:64-68, 1989.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2000
VL 6
IS 2
BP 149
EP 154
PG 6
ER
PT J
AU Cohen, AS
Trikha, M
Mascelli, AM
AF Cohen, A Sidney
Trikha, Mohit
Mascelli, A Mary
TI Potential Future Clinical Applications for the GPIIb/IIIa Antagonist, Abciximab in Thrombosis, Vascular and Oncological Indications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Abciximab; ReoPro; cardiocascular disease; angiogenesis; tumor metastasis
ID Abciximab; ReoPro; cardiocascular disease; angiogenesis; tumor metastasis
AB Abciximab (ReoPro) is a mouse-human chimeric monoclonal antibody Fab fragment of the parent murine monoclonal antibody 7E3, and was the first of these agents approved for use as adjunct therapy for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Abciximab binds with high avidity to both the non-activated and activated form of the GPIIb/IIIa receptor of platelets, the major adhesion receptor involved in aggregation. Additional cardiovascular indications for abciximab are unstable angina, carotid stenting, ischemic stroke and peripheral vascular diseases. Abciximab also interacts with two other integrin receptors; the a av b b3 receptor, which is present in low numbers on platelets but in high density on activated endothelial and smooth muscle cells, and a aMb b2 integrin which is present on activated leukocytes. Cell types that express integrins GPIIb/IIIa and a av b b3 such as platelets, endothelial and tumor cells have been implicated in angiogenesis, tumor growth and metastasis. Since abciximab interacts with high avidity to integrins GPIIb/IIIa and a av b b3 , it is reasonable to assume that it may possess anti-angiogenic properties in angiogenesis-related diseases, as well as anti-metastastatic properties in case of disseminating tumors expressing the target integrin receptors.
C1 [Cohen, A Sidney] Cenrocor Inc., 200 Great Valley Parkway, 19355 Malvern, PA, USA.
[Trikha, Mohit] Cenrocor Inc., 200 Great Valley Parkway, 19355 Malvern, PA, USA.
[Mascelli, A Mary] Cenrocor Inc., 200 Great Valley Parkway, 19355 Malvern, PA, USA.
RP Mascelli, AM (reprint author), Cenrocor Inc., 19355 Malvern, USA.
EM mascelli@centocor.com
CR Davies MJ, Thomas AC, Knapman PA, et al: Intra myocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 73:418-427, 1986.
Coller BS: The role of platelets in arterial thrombosis and the rationale for blockade of platelet IIb/IIIa receptors as antithrombotic therapy. Eur Heart J 16:11-15, 1995.
International Stroke Trial Collaborative Group: The International Stroke Trial, IST): a randomized trial of aspirin, subcutaneous heparin, both or neither among 19,435 patients with acute ischemic stroke. Lancet 349:1569-1581, 1997.
Chinese Acute Stroke Trial, CAST): Randomized placebocontrolled trial of early aspirin use in 20,000 patients with subacute ischemic stroke. Lancet 349:1641-1649, 1997.
De Scheerder I, Wang K, Wilczek K, et al: Experimental study of thrombogenicity and foreign body reaction induced by heparin-coated stents. Circulation 95(6):1549-1553, 1997.
Michelson AD, Furman MI: Laboratory markers of platelet activation and their clinical significance. Curr Opin Hematol 6:342-348, 1999.
Ferguson JJ, Waly HM, Wilson JM: Fundamental of coagulation and glycoprotein IIb/IIIa receptor inhibition. Am Heart J 134:S35-S42, 1998.
Lefkovitz J, Plow EF, Topol EJ: Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. New Eng J Med 332:1553-1559, 1995.
EPIC Investigators: Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Eng J Med 330:956-961, 1994.
The EPILOG Investigators: Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. New Eng J Med 336:1689-1696, 1997.
CAPTURE Investigators: Randomised placebo controlled trial of abciximab before, during and after coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 349:1429-1435, 1997.
The EPISTENT Investigators: Randomised placebo-controlled and balloon angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein IIb-IIIa blockade. Lancet 352:87-92, 1998.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 163
EP 174
PG 12
ER
PT J
AU Andras, Cs
Csiki, Z
Gal, I
Takacs, I
Antal, L
Szegedi, Gy
AF Andras, Csilla
Csiki, Zoltan
Gal, Istvan
Takacs, Istvan
Antal, Lajos
Szegedi, Gyula
TI Retrospective Evaluation of 5-fluorouracil-interferon-a aTreatment of Advanced Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE advanced colorectal cancer; interferon; 5-FU; survival
ID advanced colorectal cancer; interferon; 5-FU; survival
AB The authors describe the retrospective analysis of treatment by 5-fluorouracil and interferon-a aof 34 patients with advanced colorectal cancer. An average of 4.6 treatment cycles (3–12) was applied. Complete remission was not observed; partial remission was observed in 8 patients; in 13 patients no change occurred and progression was detected in 14 cases. Remission rate was 22.8%, mean response time was 5.2 (3–12) months, mean progress-free survival 5.6 (0–22) months. Mean survival from the start of treatment was 11.9 (1–42) months and from the establishment of the diagnosis 26.1 (3–60) months. Severe life-threatening side-effects did not occur; other side-effects such as fever, nausea, diarrhea, leucopenia, and anemia responded to drugs. Treatment by 5-FU and interferon, in accordance with other authors’ findings, improved survival and well-being of patients but no breakthrough has been achieved.
C1 [Andras, Csilla] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. Krt. 22., H-4004 Debrecen, Hungary.
[Csiki, Zoltan] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. Krt. 22., H-4004 Debrecen, Hungary.
[Gal, Istvan] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. Krt. 22., H-4004 Debrecen, Hungary.
[Takacs, Istvan] Medical Faculty, University of Debrecen, 2 nd Department of SurgeryDebrecen, Hungary.
[Antal, Lajos] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. Krt. 22., H-4004 Debrecen, Hungary.
[Szegedi, Gyula] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. Krt. 22., H-4004 Debrecen, Hungary.
RP Andras, Cs (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, H-4004 Debrecen, Hungary.
CR Bleiberg H: Colorectal Cancer – Is there an alternative to 5FU? Eur J Cancer 33:536-541, 1997.
Burke D, Allan-Mersh TG. Colorectal liver metastases. Postgrad Med J 72:464-469, 1996.
Gamelin EC, Danquechin-Dorval EM, et al: Relationship between 5FU dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5FU. Cancer 77:441-451, 1996.
Dufour P and Husseini F.5-fluorouracil plus alpha interferon as treatment of metastatic colorectal carcinoma. Ann Oncol 7:575- 579, 1996.
Ferguson JE, Hulse P, Lorigan P, et al: Coninuous infusion of 5 fluorouracil with alpha 2b interferon for advanced colorectal carcinoma. Brit J Cancer 72:193-197, 1995.
Jaeck D, Bachellier P, Guiguet M, et al: Long-term survival following resection of coloretal hepatic metastases. British J Surg 84:977-980, 1997.
Kemeny N, Jounes A, Seiter K, et al: Interferon alpha 2a and 5 fluorouracil for advanced colorectal carcinoma. Assesment of activity and toxicity. Cancer 66:2470-2475, 1990.
Meadows ML, Linley C: Biochemical and pharmacolgic modulation of fluorouracil by alpha interferon. Advanced colorectal cancer: The role of alpha interferons. Schering Plough International 18:10-14, 1992.
Niederle N, Kreuser ED, Meadows LM, et al: Advanced colorectal cancer . The role of alpha interferons. Schering Plough International 18:14-18, 1992.
Pazdur R, Ajani JA, Patt YZ: Phase II study of fluorouracil and recombinant interferon alpha 2a in previously untreated advanced colorectal carcinoma. J Clin Oncol 8:2027-2031, 1990.
Piga A, Cascinu S, Latini L, et al: A phase II randomised trial of 5-fluorouracil with or without intferon alpha-2a in advanced colorectal cancer. British J Cancer 74:971-974, 1996.
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Ragnhammar P, Blomgren H, Edler D, et al: Different dose regimens of 5-fluorouracil and interferon alpha in patients with metastatic colorectal carcinoma. Eur J Cancer 31:310-320, 1995.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 175
EP 178
PG 4
ER
PT J
AU Baintner, K
Jakab, G
Gyori, Zs
Kiss, P
AF Baintner, Karoly
Jakab, Gabor
Gyori, Zsuzsa
Kiss, Peter
TI Binding of FITC-Labelled Lectins to the Gastrointestinal Epithelium of the Rat
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE rat; gut; stomach; lectin; ConA; LCA; PHA; RPA; PNA; WGA; SNA; UEA
ID rat; gut; stomach; lectin; ConA; LCA; PHA; RPA; PNA; WGA; SNA; UEA
AB Biotechnology uses lectin genes to transfect into crop plants for protection against insects and nematodes. On the other hand, the information is limited on lectin-binding properties of cells in the gastrointestinal tract. Therefore, binding of a panel of FITC-labelled plant lectins to gastrointestinal cells of the rat was studied. In the stomach, cytoplasmic staining of parietal cells by PHA appeared to be due to glycoproteins attached to the tubulovesicles. PNA also stained the parietal cells, but only in the isthmus and neck regions, reacting with desialylated glycoproteins. WGA bound to the mucous neck cells with higher affinity than to the surface and foveolar mucous cells. The mucous cells were also stained by SNA-I, UEA-I and, less intensively, by LCA. Chief cells did not show detectable reaction with any of the applied lectins. Binding of PHA to gastric cells showed differences when compared with the results of in vivostudies. Small intestinal brush border was stained with UEA-I and SNA-I, the latter lectin also strongly stained the surface of small intestinal crypts. Both lectins reacted with the mucus of goblet cells. In the large intestine UEA-I and SNA-I stained the goblet cells at the base and upper part of the crypts, respectively. Accordingly, we provided evidences for the unique lectin-binding phenotype of the various segments of the gastrointestinal tract.
C1 [Baintner, Karoly] Faculty of Animal Science, University of Kaposvar, Department of Physiology, H-7401 Kaposvar, Hungary.
[Jakab, Gabor] Uzsoki Hospital, Department of NeurologyBudapest, Hungary.
[Gyori, Zsuzsa] Uzsoki Hospital, Department of NeurologyBudapest, Hungary.
[Kiss, Peter] University of Agriculture, Department of Agricultural ChemistryGodollo, Hungary.
RP Baintner, K (reprint author), Faculty of Animal Science, University of Kaposvar, Department of Physiology, H-7401 Kaposvar, Hungary.
EM baintner@atk.kaposvar.pate.hu
CR Bardocz S, Grant G, Ewen SWB, et al: Reversible effect of phytohaemagglutinin on the growth and metabolism of rat gastrointestinal tract. Gut 37:353-360,1995.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 179
EP 182
PG 4
ER
PT J
AU Gharagozloo, S
Sharifian, AR
Mageed, AR
Shokri, F
AF Gharagozloo, Soheila
Sharifian, A Ramazan
Mageed, A Rizgar
Shokri, Fazel
TI Analysis of the Expressed Immunoglobulin Variable Region Heavy Chain Gene Products in Paraproteins from Iranian Patients with Multiple Myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; VH genes; paraprotein; cross-reactive idiotype
ID multiple myeloma; VH genes; paraprotein; cross-reactive idiotype
AB The frequency of expression of immunoglobulin (Ig) variable region heavy (VH ) chain gene products was studied in 43 Iranian patients with mutiple myeloma (MM). The expressed VH gene families and associated cross-reactive idiotypes (CRI) were analysed by immunoblotting and ELISA, using peptide-induced polyclonal antibodies specific for VH 1-VH 6 gene families and monoclonal antibodies (MAb) recognising CRI linked to theVH 1, VH 3, VH 4 and VH 6 gene families. The results revealed that the VH 3 family (60.5%) was the most predominant gene family. In contrast, no paraproteins were encoded by genes from the VH 2 gene family and only 2.3% were encoded by the VH 5 family. The panel of paraproteins tested rarely expressed the probed VH -associated CRI. Our results suggest that: 1-The Ig VH genes, may not be randomly expressed in the malignant plasma cells from Iranian patients with MM. 2- Some of the genes seem to be negatively selected or highly mutated, as evidenced by the lack of expression of the probed CRI.
C1 [Gharagozloo, Soheila] School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
[Sharifian, A Ramazan] School of Medicine, Tehran University of Medical Sciences, Clinic of Hematology and OncologyTehran, Iran.
[Mageed, A Rizgar] School of Medicine, Tehran University of Medical Sciences, Clinic of Hematology and OncologyTehran, Iran.
[Shokri, Fazel] School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
RP Shokri, F (reprint author), School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 185
EP 190
PG 6
ER
PT J
AU Volavsek, M
Masera, A
Ovcak, Z
AF Volavsek, Metka
Masera, Andrej
Ovcak, Zdenka
TI Incidental Prostatic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; prostate; incidental carcinoma; transurethral resection
ID angiogenesis; prostate; incidental carcinoma; transurethral resection
AB Incidental prostatic carcinoma (ICP) has good prognosis related to low stage at diagnosis. Few rogressive cases demanding aggressive treatment need early identification. Neoangiogenesis proved its predictive role in prostatic carcinoma after radical prostatectomy. To reveal its value in ICP authors investigated specimens after transurethral resection of prostate (TURP). Retrospective study was performed on 68 ICP diagnosed in years 1985–1989. Microvessels highlighted by factor VIII were counted in a x200 microscope field (0,8012 mm 2 ) in most active areas of neovascularisation. Microvessel count was correlated with tumor differentiation degree, Gleason score, disease stage, and patients’ survival in at least 9 years after diagnosis. Higher maximal microvessel counts were associated with lower degree of tumor differentiation (p=0,005), Gleason score (p=0,001), and disease stage (0,003). No association with disease progression and patients’ survival was found. Mean microvessel counts showed less significant values when correlated with tumor differentiation degree (p=0,003) and Gleason score (p=0,01), and no correlation with other variables. Microvessel density in TURP specimens of ICP retains its prognostic value already demonstrated in carcinoma of peripheral prostatic lobes. Maximal microvessel counts were prognostically more reliable than mean values.
C1 [Volavsek, Metka] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia.
[Masera, Andrej] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia.
[Ovcak, Zdenka] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia.
RP Volavsek, M (reprint author), University of Ljubljana, Faculty of Medicine, Institute of Pathology, 1000 Ljubljana, Slovenia.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 191
EP 196
PG 6
ER
PT J
AU Onguru,
Celasun, B
AF Onguru, Onder
Celasun, Bulent
TI Intra-hospital Use of a Telepathology System
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE telepathology; frozen section
ID telepathology; frozen section
AB Utilization of telepathology systems to cover distant geographical areas has increased recently. However, the potential usefulness of similar systems for closer distances does not seem to be widely appreciated. In this study, we present data on the use of a simple telepathology system connecting the pathology department and the intra-operative consultation room within the operating theaters of the hospital. Ninety-eight frozen section cases from a past period have been re-evaluated using a real-time setup. Forty-eight of the cases have been re-evaluated in the customary fashion; allowing both ends to communicate and cooperate freely. Fifty of the cases, however, were evaluated by the consultant while the operating room end behaved like a ''robot”; moving the stage of the microscope, changing and focusing the objectives. The deferral rate was lower than the original frozen section evaluations. Overall, the sensitivity was 100%, specificity 98%, negative predictive value 96,5% and positive predictive value 100%. No significant difference was found for the diagnostic performances between the cooperative and robotic simulation methods.Our results strengthen the belief that telepathology is a valuable tool in offering pathology services to remote areas. The far side of a hospital building can also be a remote area and a low cost system can be helpful for intraoperative consultations. Educational value of such a system is also commendable.
C1 [Onguru, Onder] Gulhane Medical Military Academy, Department of Pathology, Etlik, 06018 Ankara, Turkey.
[Celasun, Bulent] Gulhane Medical Military Academy, Department of Pathology, Etlik, 06018 Ankara, Turkey.
RP Onguru, (reprint author), Gulhane Medical Military Academy, Department of Pathology, 06018 Ankara, Turkey.
CR Callas PW, Leslie KO, Mattia AR, et al: Diagnostic accuracy of a rural live video telepathology system. Am J of Surg Pathol 21:812-819, 1997.
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Dunn BE, Almagro UA, Choi H, et al: Dynamic-robotic telepathology: Department of Veterans Affairs feasibility study. Hum Pathol 28:8-12, 1997.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 197
EP 201
PG 5
ER
PT J
AU Tokes, AM
Paku, S
Toth, S
Paal, E
Kulka, J
Toth, J
Telekes, A
AF Tokes, Anna-Maria
Paku, Sandor
Toth, Sara
Paal, Edina
Kulka, Janina
Toth, Jozsef
Telekes, Andras
TI Tenascin Expression in Primary and Recurrent Breast Carcinomas and the Effect of Tenascin on Breast Tumor Cell Cultures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tenascin; breast cancer; cell cultures; focal adhesion plaques
ID tenascin; breast cancer; cell cultures; focal adhesion plaques
AB Tenascin is generally classified as an anti-adhesive protein. Many cells do not adhere to tenascin or if they adhere they do not spread. In this study we analysed the stromal expression of tenascin-C in primary, second primary and recurrent breast carcinomas and the ability of tenascin-C to stimulate the focal adhesion plaques in MDA-MB-435 breast carcinoma cell line. To assess the tenascin-C expression formalin-fixed, paraffin-embedded specimens of 20 specially selected breast carcinomas and their recurrences (14) or a second primary breast cancer of the same patient (6) were examined with immunohistochemical methods. We also studied the effect of tenascin-C on focal adhesion plaques added to MDA-MB-435 breast carcinoma cell line. During a median 2,9-year patient follow up 14 local recurrences and 6-second primary breast carcinomas developed in the 20 patients. In 3 cases a second recurrence occurred. The presence of tenascin in tumor cells, in the proliferating and some normal ducts, near to the tumor cell nests, in the stroma and in ductal carcinoma in situ component of the invasive carcinoma may suggest the role of tenascin played in tumor cell migration. Soluble tenascin added to the cell culture had minimal or no effect on focal adhesion plaques. Tenascin only seems not to be of prognostic value in predicting the local recurrence of breast cancer.
C1 [Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Toth, Sara] Semmelweis University, Department of Genetics, Cell and ImmunobiologyBudapest, Hungary.
[Paal, Edina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Toth, Jozsef] National Institute of OncologyBudapest, Hungary.
[Telekes, Andras] National Institute of OncologyBudapest, Hungary.
RP Tokes, AM (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
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Shaw LM, Chao C, Wewer UM, et al: Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor. Cancer Res 56:959-963, 1996.
Shoji T, Kamiya T, Tsubura A, et al: Immunohistochemical staining patterns of tenascin in invasive breast carcinomas. Virchows Archiv A Pathol Anat. 421:53-56, 1992.
Sriramarao P, Mendler M, Bourdon MA: Endothelial cell attachment and spreading on human tenascin is mediated by alpha 2 beta 1 and alpha v beta 3 integrins. J Cell Sci. 105:1001- 1012, 1993.
Taylor HC, Lightenasciner VA, Beyer WF, et al: Biochemical and structurel studies of tenascin/hexabranchion proteins. J Cell Biochem 41:71-90, 1989.
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Tremble P, Chiquet-Ehrismann R, Werb Z: The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol Biol Cell 5:439-453, 1994.
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Yoshida T, Ishihara A, Hirokawa Y, et al: Tenascin in breast cancer development-is epithelial tenascin a marker for poor prognosis. Cancer Lett 90:65-73, 1995.
Yoshida T, Matsumoto E, Hanamura N, et al: Co-expression of tenascin and fibronectin in epithelial and stromal cells of beningn lesions and ductal carcinomas in the human breast. J Pathol 182:421-428, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 202
EP 209
PG 8
ER
PT J
AU Rubio, L
Burgos, J
Morera, C
Vera-Sempere, F
AF Rubio, Luis
Burgos, S. Javier
Morera, Calderon
Vera-Sempere, J. Francisco
TI Morphometric Study of Tumor Angiogenesis as a New Prognostic Factor in Nasopharyngeal Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; morphometry; nasopharyngeal carcinona
ID angiogenesis; morphometry; nasopharyngeal carcinona
AB The aim of this study was to determine the possible prognostic significance of tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients. Fifty-five NPC patients were evaluated in relation to survival. Endothelial cells were immunohistochemically stained with anti-von Willebrand factor (F-VIII), CD-31 and CD-34 antibodies, and microvessels counted in the most active areas of tumor neovascularization or hotspotsusing both a manual and an automatic method. Overall survival analysis calculated by the Kaplan–Meiertest revealed that both methods were correlated with a statistical significance between intratumoral microvessel density (IMD) and overall survival, using either manual (p=0.0141) or automatic counting (p=0.0117). Other angiogenic parameters studied were perimeter, roundness and accumulative area of the microvessels using a morphometric analyzer. Moreover, our results show that cases with high IMD demonstrated a prognostic significance in relation to the accumulative area (p=0.0072).
C1 [Rubio, Luis] University of Valencia, Department of Pathology, Avda. Campanar 21, 46009 Valencia, Spain.
[Burgos, S. Javier] CSIC-Autonomous University of Madrid, Center of Molecular Biology, Severo OchoaMadrid, Spain.
[Morera, Calderon] University Hospital La Fe, Service of ORLValencia, Spain.
[Vera-Sempere, J. Francisco] University of Valencia, Department of Pathology, Avda. Campanar 21, 46009 Valencia, Spain.
RP Vera-Sempere, F (reprint author), University of Valencia, Department of Pathology, 46009 Valencia, Spain.
CR Nicholls JM: Nasopharyngeal carcinoma: classification and histologic appearances. Adv. Anat. Pathol. 4:71-84, 1996.
Vera-Sempere FJ, Burgos JS, Botella MS, et al: Immunohistochemical expression of Epstein-Barr virus, EBV)-encoded latent membrane protein, LMP-1, in paraffin sections of EBVassociated nasopharyngeal carcinoma, NPC, in Spanish patients. Oral Oncol Eur J Cancer 32B:163-166, 1996.
Vera-Sempere FJ, Burgos JS, Botella MS: Comparative analysis of Epstein-Barr virus, EBV, detection by nested-PCR and nonisotopic in situ hybridization, NISH, in nasopharyngeal carcinoma. Clin Chem Acta 271:119-132, 1998.
Liebowitz D: Nasopharyngeal carcinoma: the Epstein-Barr virus association. Semin. Oncol. 21:376-381, 1994.
Shanmugaratnam K, Sobin LH: Histological typing of upper respiratory tract tumors. International histological classification of tumors, WHO, Geneva 19:20-32, 1978.
Norrby K: Angiogenesis: new aspects relating to its initiation and control. APMIS 105:417-437, 1997.
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Weidner N, Semple JP, Welch WR, et al: Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1-8, 1991.
Weidner N, Folkman J, Pozza F, et al: Tumor angiogenesis: a new significant and independent prognostic indicator in earlystage breast carcinoma. J Natl Cancer Inst 84:1875-1887, 1992.
Toi M, Kashitani J, Tominaga T:Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer 55:371-374, 1993.
Ogawa Y, Chung Y-S, Nakata B, et al: Microvessel quantitation in invasive breast cancer by staining for factor VIII-related antigen. Br J Cancer 71:1297-1301, 1995.
Fontanini G, Bigini D, Vignati S, et al: Microvessel count predicts metastatic disease and survival in non-small cell cancer. J Pathol 177:57-63, 1995.
Simpson JF, Ahn C, Battifora H, et al: Endothelial area as a prognostic indicator for invasive breast carcinoma. Cancer 77:2077-2085, 1996.
Micheau C: What’s new in histological classification and recognition of nasopharyngeal carcinoma, NPC)? Path Res Pract 181:249-253, 1986.
De Jong JS, Van Diest PJ, Baak JPA: Heterogeneity and reproducibility of microvessel counts in breast cancer. Lab Invest 73:922-926, 1995.
Tomisaki S, Ohno S, Ichiyoshi Y, et al: Microvessel quantification and its possible relation with liver metastasis in colorectal cancer. Cancer 77:1722-1728, 1996.
Tanigawa N, Matsumara M, Amaya H, et al: Tumor vascularity correlates with the prognosis of patients with esophageal squamous cell carcinoma. Cancer 79:220-225, 1997.
Quian CN, Min HQ, Liang XM, et al: Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis. J Cancer Res Clin Oncol 123:645-651, 1997.
Roychowdhury DF, Tseng Jr. A, Fu KK, et al: New prognostic factors in nasopharyngeal carcinoma. Tumor angiogenesis and C-erbB2 expression. Cancer 77:1419- 1426, 1996.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 210
EP 216
PG 7
ER
PT J
AU Bhattacharya, P
Maity, P
AF Bhattacharya, Pritha
Maity, Putul
TI Localization of Phosphate Dependent Glutaminase in Ascites Fluid of Ovarian Cancer Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; ascites fluid; glutaminase
ID Ovarian cancer; ascites fluid; glutaminase
AB Phosphate dependent glutaminase was purified from ascites fluid of ovarian cancer patients. The purified enzyme showed a final specific activity of 110 unit / mg protein with 72 fold purification and 21% yield. Purified enzyme gives one dark band of Mr ~65.5 KD and two light bands of Mr ~47.5 KD and ~45 KD respectively on 10% SDS-PAGE. One major immunoreactive band was found in trans-immunoblot analysis using antibodies against rat kidney and ascites fluid glutaminase raised in rabbit and mice respectively. Phosphate dependent glutaminase enzyme purified from mitochondria of malignant and non malignant ovarian tissue also showed bands of same molecular weight on 10% SDS-PAGE and gave same immunoreactive bands in trans-immunoblot like the purified glutaminase from ascites fluid. This result was confirmed by using the specific activity stain for glutaminase, which indicates that same enzyme activity is probably due to leakage of the same enzyme from malignant tissue into the ascites fluid. The purified enzyme from human peritoneal fluid showed a high specificity toward glutamine, therefore is a true glutaminase. Moreover, ascites fluid taken from patients of different age group with different stages of ovarian carcinoma revealed the presence of same glutaminase on 10% SDS-PAGE, and exhibited immunoreaction on ELISA, trans-immunoblot and dot immunoblot analysis.
C1 [Bhattacharya, Pritha] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 16, 700 026 Calcutta, India.
[Maity, Putul] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 16, 700 026 Calcutta, India.
RP Maity, P (reprint author), Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 700 026 Calcutta, India.
CR Newsholm EA, Parry-Billings M: Properties of glutamine released by skeletal muscle and its importance to the immune system. J Parenter Enter Nutr 14:63S, 1990.
Newsholm EA, Crabtree B, Ardawi MSM: Glutamine metabolism in lymphocytes, its biochemical, physiological and clinical importance. Q J Exp Physiol 70:473-489, 1985.
Watford M: Glutamine metabolism in the small intestine: synthesis of three carbon end products in isolated enterocytes. Biochim Biophys Acta 120:73-78, 1994.
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Windmueller HG, Spaeth AE: Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 249:5070- 5079,1974.
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Maity P, Chakraborty S, Bhattacharya P, et al: Isolation and purification of phosphate dependent glutaminase from Sarcoma- 180 tumor and its antineoplastic effects on murine model system: J Exp Clin Cancer Res 18:475-480,1999.
Pal S, Maity P: Investigation on glutamine amidohydrolase, EC3.5.1.2, and glutamine aminotransferase, EC 2.5.1.15, activity in liver and plasma of EAC bearing mice following glutaminase therapy. Cancer Letters 66:225-231,1992.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 217
EP 223
PG 7
ER
PT J
AU Szekely, E
Schaff, Zs
Madaras, L
Kupcsulik, P
Zsirka, A
AF Szekely, Eszter
Schaff, Zsuzsa
Madaras, Lilla
Kupcsulik, Peter
Zsirka, Attila
TI Trabecular Angiomyolipoma Mimicking Hepatic Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE hepatic tumor; angiomyolipoma; trabecular; epithelioid
ID hepatic tumor; angiomyolipoma; trabecular; epithelioid
AB Hepatic angiomyolipomas are rare tumors, especially in comparison with those occurring in the kidney. Nevertheless, it is important to be aware of their existence, especially when occurring in the liver, where they might have different subtypes. Not infrequently they are composed of rather irregular cells with epithelioid appearance. In these cases hepatocellular carcinoma or the possibility of other malignant tumors has to be ruled out, with the aid of numerous immunohistochemical reactions. The authors present a case of a female patient, whose liver lesion was first diagnosed on cytological examination as a hepatocellular carcinoma. Based on the preoperative cytological diagnosis, a large liver lobe resection was performed. Histological examination found an angiomyolipoma of the above-mentioned type, and the final diagnosis was ascertained with the aid of vimentin, smooth muscle actin (SMA), and HMB-45.
C1 [Szekely, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Madaras, Lilla] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kupcsulik, Peter] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Zsirka, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
RP Szekely, E (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM szesz@korb2.sote.hu
CR Tsui WMS, Colombari R, Portmann BC: Hepatic angiomyolipoma A clinicopathologic study of 30 cases and delineation of unusual morphologic variants Am J Surg Pathol 23:34-48, 1999.
Chan JKC, Tsang WYW, Pau MY, et al: Lymphangiomyomatosis and angiomyolipoma:closely related entities characterized by hamartomatous proliferation of HMB-45 positive smooth muscle. Histopathology 22:445-455, 1993.
Eble JN, Amin MB, Young RH: Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol 21:1123-1130, 1997.
Guinee DG, Thornberry DS, Azumi N, et al: Unique pulmonary presentation of an angiomyolipoma. Am J Surg Pathol 19:476- 480, 1995.
Martignoni G, Pea M, Bonetti, et al: Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence of tuberous sclerosis: a clinicopathologic and genetic study. Am J Surg Pathol 22:663-672, 1998.
Nonomura A, Mizukami Y, Muraoka K: Angiomyolipoma of the liver with pleomorphic histological features. Histopathology 24:279-281, 1994.
Kaiserling E, Krober S. XiaoJ-C, et al: Angiomyolipoma of the kidney. Immunoreactivity with HMB-45, light and electronmicroscopic findings. Histopathology 25:41-48, 1994.
Wick MR, Humphrey PA, Ritter JH: Pathology of pseudoneoplastic lesions. Lippincott-Raven, 1997, pp 163-165.
Sturtz CL, Dabbs DJ: Angiomyolipomas: the nature and expression of the HMB45 antigen. Mod, ???, Pathol 7:842-845, 1994.
Tsui WMS, Yuen AKT, Ma KF, et al: Hepatic angiomyolipoma with deceptive trabecular pattern and HMB-45 reactivity. Histopathology 21:569-573, 1992.
Tsui WMS, Ng IOL, Colombary R, et al: Hepatic angiomyolipomas, letter). Histopathology 22: 602-603, 1993.
Ma TKF, Tse MK, Tsui WMS, et al: Fine needle aspiration diagnosis of angiomyolipoma of the liver using a cell block with immunohistochemical study. A case report. Acta Cytol 38:257- 260, 1994.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 224
EP 226
PG 3
ER
PT J
AU Sergi, C
Bohler, Th
Schonrich, G
Sieverts, H
Roth, US
Debatin, KM
Herwart, FO
AF Sergi, Consolato
Bohler, Thomas
Schonrich, Gunther
Sieverts, Hauke
Roth, U Stephanie
Debatin, Klaus-Michael
Herwart, F Otto
TI Occult Thyroid Pathology in a Child with Acquired Immunodeficiency Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE HIV; AaS; childhood; thyroid gland; pathology
ID HIV; AaS; childhood; thyroid gland; pathology
AB A 11-year-old boy with acquired immunodeficiency syndrome (AaS), Varicella-zoster virus (VZV) infection and long-term antiviral treatment suffered from a disorder of contractility of the left ventricle of the heart. Following severe unmanageable vomiting, the patient died and the postmortem examination showed marked involution of the lymphatic system, multiple foci of fibrosis of both ventricles of the heart, and regressive changes of the thyroid gland. Biochemical values of the thyroid gland function were, however, not altered. Neither human immunodeficiency virus-related p24 antigen, nor VZV DNA sequences were found in the thyroid gland. Regressive changes of the thyroid gland can probably occur before its function fails. By analyzing the possible etiologies, the endocrine toxicity of a long-term antiviral treatment should be taken into account.
C1 [Sergi, Consolato] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Bohler, Thomas] University of Ulm, Department of PediatricsUlm, Germany.
[Schonrich, Gunther] University of Heidelberg, Institute of Hygiene and MicrobiologyHeidelberg, Germany.
[Sieverts, Hauke] University of Heidelberg, Department of PediatricsHeidelberg, Germany.
[Roth, U Stephanie] University of Heidelberg, Department of NeuropathologyHeidelberg, Germany.
[Debatin, Klaus-Michael] University of Ulm, Department of PediatricsUlm, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
RP Sergi, C (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM Consolato_Sergi@med.uni-heidelberg.de
CR Bakshi SS, Britto P, Capparelli E, et al: Evaluation of pharmacokinetics, safety, tolerance, and activity of combinadon of zalcitabine and zidovudine in stable, zidovudinetreated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team. J Infect Dis 175:1039- 1050, 1997.
Blumberg BS, Fox RC: The Daedalus effect: changes in ethical questions relating to hepatitis B virus. Ann Intern Med 102:390-394, 1985
Butler KM, Venzon D, Henry N, et al: Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine. Pediatrics 91:747-751, 1993.
Callea F, Fabbretti G, Brisigotti M, et al Valutazione della patologia da farmaci nel bambino. In: „Farmaci e Bambino. Terapia pediatrica essenziale e principi di farmacologia“. Durand P & Cornaglia-Ferraris P, eds). Casa Editrice Ambrosiana, Milano, 1993, pp. 23-33.
Cohen J: AIDS therapy. Failure isn’t what it used to be...but neither is success. Science 279:1133-1134, 1998.
Desai G, Islam R: The changing pattern of surgical pathology of the thyroid gland in Zambia. Cent Afr J Med 38:240-242, 1992.
Domanski MJ, Sloas MM, Follmann DA, et al: Effect of zidovudine and didanosine treatment on heart function in children infetted with human immunodeficiency virus. J Pediatr 127:137-146, 1995.
Edelman M, Birkenhauer MC, Steinberg JJ, et al: Microglial nodule encephalitis: limited CNS infection despite disseminated systemic cryptococcosis. Clin Neuropathol 15:30-33, 1996.
Englund JA, Baker CJ, Raskino C, et al: Zidovudine, didanosine, or both as the initial treatment for symptomatic HIVinfected children. AIDS Clinical Trials Group, ACTG, Study 152 Team. N Engl J Med 336:1704-1712, 1997.
Hannet I, Erkeller-Yuksel F, Lydyard P, et al: Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today 13:215-218, 1992.
Hirschfeld S: Use of human.recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection. Horm Res 46:215- 221, 1996.
Hirschfeld S, Laue L, Cutler GB Jr, et al: Thyroid abnormalities in children infected with human immunodeficiency virus. J Pediatr 128:70-74, 1996.
Hoernle EH, Reid TE: Human immunodeficiency virus infection in children. Am J Health Syst Pharm 52:961-979, 1995.
Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex, ABC, in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody, PAP, procedures. J Histochem Cytochem 29:577-580, 1981.
Joshi VV: Pathology of childhood AIDS. Pediatr Clin North Am 38:97-120, 1991.
Kamali F: Clinical pharmacology of zidovudine and other 2’;3’- dideoxynucleoside analogues. Clin Investig 71:392-405, 1993.
Keyhani-Rofagha S, Piquero C: Pneumocystis carinii thyroiditis diagnosis by fme needle aspiration cytology: a case report. Acta Cytol 40:307-310, 1996.
Lacaille F, Ortigao MB, Debre M, et al: Hepatic toxicity associated with 2’-3’ dideoxyinosine in children with AIDS. J Pediatr Gastroenterol Nutr 20:287-290, 1995.
Levin TL, Berdon WE, Tang HB, et al: Dideoxyinosine-induced pancreatitis in human immunodeficiency virus-infected children. Pediatr Radiol 27:189-191, 1997.
Luzuriaga K, Bryson Y, McSherry G, et al: Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis 174:713-721, 1996.
Matarazzo P, Palomba E, Lala R, et al: Tovo PA: Growth impairment, IGF I hyposecretion and thyroid dysfunction in children with perinatal HIV-1 infection. Acta Paediatr 83:1029-1034, 1994.
Mueller BU, Butler KM, Stocker VL, et al: Clinical and pharmacokinetic evaluation of long-term therapy with didanosine in children with HIV infection. Pediatrics 94:724-731, 1994.
Pizzo PA, Butler K, Balis F, et al: Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection. J Pediatr 117:799-808, 1990.
Puchhammer-Stockl E: PCR detection of varicella zoster virus. In: Persing DH, Snith TF, Tenover FC, White TJ, eds). Diagnostic molecular microbiology. Principles and applications. American Society for Microbiology, Washington, 1993, pp. 356-360.
Schwartz LJ, St Louis Y, Wu R, et al: P: Endocrine function in children with human immunodeficiency virus infection. Am J Dis Child 145:330-333, 1991.
Sergi C, Bohler T, Schonrich G, et al: Pediatric Acquired Immunodeficiency Syndrome, PAIDS, as viewed by the pathologist and the immunologist: up-dated review. Pediatr Grenzgeb, Pediatrics and related topics, 37:271-332, 1998.
Whitcup SM, Dastgheib K, Nussenblatt RB, et al: A clinicopathologic report of the retinal lesions associated with didanosine. Arch Ophthalmol 112:1594-1598, 1994.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 227
EP 232
PG 6
ER
PT J
AU Szekely, E
Kulka, J
Miklos, I
Kaliszky, P
AF Szekely, Eszter
Kulka, Janina
Miklos, Imre
Kaliszky, Peter
TI Leiomyosarcomas of Great Vessels
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE leiomyosarcoma; thoracic aorta; aortic dissection; inferior vena cava; retroperitoneal tumor
ID leiomyosarcoma; thoracic aorta; aortic dissection; inferior vena cava; retroperitoneal tumor
AB Sarcomas of the great vessels are rare. Altogether 400 such cases have been described in the aorta, the pulmonary artery, and inferior vena cava. The clinical symptoms are generally related to embolic phenomena, aneurysm formation, and widespread metastases, especially to bones. With improved diagnostic modalities more cases are diagnosed and treated surgically. Resection of the tumor may prolong the patient’s life. In this paper authors present two cases of such rare sarcomas. In our first case a tumor has developed in the thoracic aorta with symptoms of imminent aortic dissection. The tumorous nature of the lesion was revealed only histologically, since neither the operation, nor macroscopic picture gave any clue to its tumorous nature. The second case was a male patient with a huge retroperitoneal tumor arising from the inferior vena cava, which was clinically suspected to be a carcinomaarising in the adrenal gland.
C1 [Szekely, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Miklos, Imre] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Kaliszky, Peter] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
RP Szekely, E (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM szesz@korb2.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2000
VL 6
IS 3
BP 233
EP 236
PG 4
ER
PT J
AU Rosendaal, M
Krenacs, T
AF Rosendaal, Martin
Krenacs, Tibor
TI Regulatory Pathways in Blood-forming Tissue with Particular Reference to Gap Junctional Communication
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Direct cell-cell communication; gap junctions; connexin 43; growth factors; regulation of haemopoesis; haemopoietic microenvironment
ID Direct cell-cell communication; gap junctions; connexin 43; growth factors; regulation of haemopoesis; haemopoietic microenvironment
AB Blood formation by pluripotent stem cells and their progeny is thought to be regulated by receptor-ligand interactions between cell-substrate, cell-cell and cell-matrix in the bone marrow. Primitive stem cells form progenitors and, in their turn, these give rise to haemopoietic progeny which are more specifically committed in that they can form progressively fewer types of blood cells. Recently we have estab-lished that direct cell-cell communication via gap junctions may be part of this regulatory system. Con-nexin43 gap junctions metabolically couple the three dimensional meshwork of bone marrow stromal cells to form a functional syncytium in which some blood-forming cells are also coupled. The expression of gap junctions in the bone marrow is markedly upregulated when there is an urgent and substantial demand for blood-formation; for example, following cytotoxic injury after 5-fluorouracil or irradiation; or during neonatal blood-formation and in the epiphysis of growing bones. Chemical blockade of gap junctions blocks blood-formation in long-term cultures but is reversible after the blockade has been relieved. This short review highlights briefly the known regulatory mechanisms of blood-formation with especial attention to gap junctional communication.
C1 [Rosendaal, Martin] University College London, Department of Anatomy and Developmental Biology, Gower Street, WC1E 6BT London, UK.
[Krenacs, Tibor] University of Szeged, Department of PathologySzeged, Hungary.
RP Rosendaal, M (reprint author), University College London, Department of Anatomy and Developmental Biology, WC1E 6BT London, UK.
EM m.rosendaal@ucl.ac.uk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 243
EP 249
PG 7
ER
PT J
AU Sergi, C
Kahl, P
Herwart, FO
AF Sergi, Consolato
Kahl, Philip
Herwart, F Otto
TI Immunohistochemical Localization of Transforming Growth Factor-a and Epithelial Growth Factor Receptor in Human Fetal Developing Skin, Psoriasis and Restrictive Dermopathy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TGF-a; EGFR; developing skin; psoriasis; genodermatosis
ID TGF-a; EGFR; developing skin; psoriasis; genodermatosis
AB Keratinocytes release a number of cytokines interacting with other intra- and subepidermal cells during the initiation and the perpetuation of skin inflammatory reactions. Cultured human keratinocytes overexpressing the transforming growth factor alpha (TGF-alpha) assumed a spindled morphology and displayed increased locomotion. Moreover, the receptor for TGF-alpha, the epithelial growth factor receptor (EGFR), is important for autocrine growth, promotion of cell survival, and regulation of cell migration. The expression of TGF-alpha and EGFR has not been widely studied in human developing skin and their roles in geno-dermatosis are not known. In this study, we investigated the expression of TGF-alpha and EGFR by immunohistochemistry in human developing skin at different gestational ages (14 th week, 20 th week, and 34 th week), in six patients with psoriasis, and, for the first time, in an infant affected with restrictive dermopathy, a very rare lethal genodermatosis, characterized by abnormal skin growth and differentiation with thin, tightly adherent skin. TGF-alpha and EGFR were expressed in the basal layer at the 14 th week and in all epidermal layers at the 20 th and 34 th week of gestation. In psoriasis, TGF-alpha was overexpressed in all layers of epidermis, while EGFR was expressed in the basal and first suprabasal layers. In restrictive dermopathy, we observed no expression of both TGF-alpha and EGFR at the level of the skin. The other organs showed comparable patterns to those of an age-matched infant. In conclusion, TGF-alpha and EGFR interact strictly to promote skin development during the intrauterine life. An interactive autocrine growth cycle between TGF-alpha and EGFR is present in psoriasis. A skin-localized alteration of the expression of TGF-alpha and EGFR may be at the basis of restrictive dermopathy. The delay of growth and differentiation of the skin in restrictive dermopathy may be related to the absent expression of TGF-alpha, which is probably due to a down regulation of EGFR by an abnormal autocrine mechanism.
C1 [Sergi, Consolato] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Kahl, Philip] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany.
RP Sergi, C (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM Consolato_Sergi@med.uni-heidelberg.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 250
EP 255
PG 6
ER
PT J
AU Rehman, Sh
Crow, J
Revell, AP
AF Rehman, Shazza
Crow, Julie
Revell, A Peter
TI Bax Protein Expression in DCIS of the Breast in Relation to Invasive Ductal Carcinoma and Other Molecular Markers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; ductal carcinoma in situ; Bax; Ki67; oestrogen receptor; p53; cErbB2; Bcl2
ID breast cancer; ductal carcinoma in situ; Bax; Ki67; oestrogen receptor; p53; cErbB2; Bcl2
AB This study describes the incidence of Bax protein expression in a series of 106 cases of breast cancer including 56 cases of ductal carcinoma in situ (DCIS) and 50 cases of invasive ductal carcinoma (IDC). Relationships of Bax expression to the histological grades of DCIS & IDC, and to the expression of Ki67, ER, p53, cerbB2 & Bcl2 are described. The expression of Bax, Ki67, ER, p53, cerbB2 and Bcl2 proteins is determined immunohistochemically. Cases were regarded positive for Bax, Bcl2 and cerbB2 when they showed either moderate or strong staining for these markers. The nuclear stains (Ki67, ER, and p53) were quantified in terms of percentage positive cells and cases for ER and p53 were considered positive when more than 10% cells were labelled. DCIS were graded histologically as well (n=18), intermediately (n=18), and poorly differentiated (n=20) Invasive ductal carcinoma was graded as grade I (well-differentiated) n=7, grade II (intermediate) n=24 and grade III (poorly differentiated) n=19. 65/106 cases (61%) were Bax positive including 37/56 (66%) of DCIS and 28/50 (56%) of IDC. Bax expression did not correlate to increasing histological grades of either DCIS or IDC. It did not correlate to Ki67, ER, p53 or cerbB2 but positive correlation was seen with Bcl2 (p=0.003). Bcl2 immunostaining displayed a negative correlation with increasing histological grades both of DCIS and IDC (p=0.026), (p=0.041) respectively. There was a trend of negative correlation of Bcl2 with Ki67 (p=0.062). It correlated positively with Bax (p=0.003) and ER (p<0.0001). Results suggest that the regulation of apoptosis is important in ductal carcinoma in situ of the breast as well as invasive ductal carcinomas. Bcl2 is associated with good prognostic markers in both DCIS and IDC, whereas the regulation of Bax is complex and does not necessarily correlate with mutant p53.
C1 [Rehman, Shazza] University College London Medical School, Department of Histopathology, Row-land Hill Street, NW3 2PF London, UK.
[Crow, Julie] University College London Medical School, Department of Histopathology, Row-land Hill Street, NW3 2PF London, UK.
[Revell, A Peter] University College London Medical School, Department of Histopathology, Row-land Hill Street, NW3 2PF London, UK.
RP Rehman, Sh (reprint author), University College London Medical School, Department of Histopathology, NW3 2PF London, UK.
EM shazzarehman@doctors.org.uk
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Anderson J, Thorp SM, King WJ, et al: The prognostic value of immunohistochemical oestrogen receptor analysis in paraffin embedded and frozen sections versus that of steroid binding assays. Eur J Cancer 26:442-449, 1990.
Elledge RM, Green S, Howes L, et al: Bcl2, p53 and response to lamonifen in oestrogen receptor positive metastatic breast cancer: a southwest oncology group study. J Clin Oncol 15:1916- 1922, 1997.
Holland R, Peterse JL, Millis RR, et al: Ductal carcinoma in situ: A proposal for a new classification. Seminars in Diagnostic Pathology. 11:167-180, 1994.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long term follow up. Histopathology; 19:403-410, 1991
Vilain MO, Delobelle-Deroide A, Bloget F, et al: Immunohistochemical detection of oestrogen and progesterone receptors in formation fixed, paraffin embedded tissues after microwave treatment. Comparison with biochemical assay in a series of 123 breast carcinomas with determination of the positivity cut off. Annales de Pathologie. 17:82-88, 1997.
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Kapucuoglu N, Losi L, Eusebi V: Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas. Virchows Arch 430:17-22, 1997
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Van Slooten HJ, Clahsen PC, Van Dierendonck JH: Expression of Bcl2 in node negative breast cancer is associated with various prognostic factors, but does not predict response to one course of peri-operative chemotherapy, Br J Cancer 74:78-85, 1996.
Joensuu H, Pylkkanen L, Toikkanen S: Bcl2 protein expression and long term survival in breast cancer, Amer J Pathol 145:1191-1198, 1994.
Siziopikou KP, Prioleau JE, Harris JR, et al: Bcl2 expression in the spectrum of pre-invasive breast lesions. Cancer 77:499- 506, 1996
Quinn CM, Ostrowski JL, Harkins L, et al: Loss of Bcl2 expression in DCIS of the breast relates to poor histological differentiation and to expression of p53 and cerbB2 proteins. Histopathology 3:531-536, 1998.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 256
EP 263
PG 8
ER
PT J
AU Lazaris, ChA
Chatzigianni, BE
Paraskevakou, H
Tseleni-Balafouta, S
Davaris, SP
AF Lazaris, Ch Andreas
Chatzigianni, B Emmy
Paraskevakou, Helen
Tseleni-Balafouta, Sofia
Davaris, S Panayiotis
TI Lectin Histochemistry as a Predictor of Dysplasia Grade in Colorectal Adenomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal adenomas; lectin binding; phaseolous vulgaris leucoagglutinin; ulex europaeus; wheat germ agglutinin; peanut agglutinin
ID colorectal adenomas; lectin binding; phaseolous vulgaris leucoagglutinin; ulex europaeus; wheat germ agglutinin; peanut agglutinin
AB Lectins are sugar-binding proteins that bind to specific cellular carbohydrates, commonly affecting cellular physiology. Phaseolus vulgaris leucoagglutinin (PHA), ulex europaeus isoagglutinin-I (UEA-I), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) are among the most well studied lectins in various tissues. The purpose of this study was to detect the above lectins’ binding sites and so examine alterations in glycoconjugate expression in neoplastic cells of 52 colorectal adenomas with various clinicopathologic characteristics and proliferation rates. Lectin histochemistry was performed in paraffin sections with and without neuraminidase treatment. Proliferative fraction was determined by immunolabelling for Proliferating Cell Nuclear Antigen. PHA was the more frequently positive lectin in the examined specimens; however, it was simultaneously detected in normal colonic mucosa and so was WGA. The frequency of high grade dysplasia was significantly greater in older patients and in samples with UEA-I positivity without neuraminidase pretreatment. UEA-I-reactive adenomas were generally characterized by high cell proliferation rates. A statistical model based on patients’ age and UEA-I binding without neuraminidase treatment can generally predict grade of dysplasia in 83% of adenomas and particularly high grade dysplasia in up to 93% of adenomas; so, such a model may be potentially useful for the early detection of neoplasia, for instance in exfoliative cells from the large intestine.
C1 [Lazaris, Ch Andreas] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Chatzigianni, B Emmy] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Paraskevakou, Helen] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Tseleni-Balafouta, Sofia] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
[Davaris, S Panayiotis] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
RP Lazaris, ChA (reprint author), University of Athens, Medical School, Department of Pathology, GR-115 27 Athens, Greece.
EM alazaris@cc.uoa.gr
CR Kinzler KW, Vogelstein B: Colorectal tumors. In: The Genetic Basis of Human Cancer., Eds: Vogelstein B and Kinzler KW, New York: McGraw- Hill, 1998, pp 565-587.
Ryder SDD, Parker N, Ecclestone D, et al: Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps. Gastroenterology 106:117-124, 1994.
Ohannesian DW, Lotan D, Thomas P, et al: Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells. Cancer Research 55:2191- 2199, 1995.
Mitchell BS, Schumacher U: The use of lectin Helix pomatia agglutinin, HPA, as a prognostic indicator and as a tool in cancer research. Histol Histopathol 14:217-226, 1999.
Li WP, Zuber C, Heitz PU, Roth J: Cytochemical staining for b1,6 branching of asparagine-linked oligosaccharides in variants of metastatic human colon carcinoma cells. Am J Pathol 145:470-480, 1994.
Rosai J: Ackerman’ s Surgical Pathology. Mosby, St. Louis, 1996.
Kiss R, Camby I, Duckworth C, et al: In vitro influence of Phaseolous vulgaris, Griffonia simplicifolia, Concavalin A, Wheat germ and Peanut agglutinins on HTC-15, LoVo, and SW837 human colorectal cancer cell growth. Gut 40:253- 261,1997.
Ryder SD, Smith JA, Rhodess JM: Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells. J Natl Cancer Inst 84:1410-1416, 1992.
Jordinson M, El-Harity I, Calnan D, et al: Vicia faba agglutinin, the lectin present in broad beans, stimulates differentiation of undifferentiated colon cancer cells. Gut 44 :709-714, 1999.
Said IT, Shamsuddin AM, Sherief MA, et al: Comparison of different techniques for detection of Gal-Gal N Ac, an early marker of colonic neoplasia. Histol Histopathol 14:351-357, 1999.
Sivridis E, Agnantis N: The loss of lectin reactivity from human endometrium is a feature of malignant change. Path Res Pract 192:989-997, 1996.
Lazaris ACh, Davaris P, Nakopoulou L, et al: Correlation between immunohistochemical expression of proliferating cell nuclear antigen and flow cytometry parameters in colorectal neoplasia. Dis Colon Rectum 37:1083-1089, 1994.
Brink U, Bosbach R, Korabiowska M, et al: Histochemical study of expression of lectin-reactive carbohydrate epitopes and glycoligand-binding sites in normal human appendix vermiformis, colonic mucosa, acute appendicitis and colonic adenoma. Histol Histopathol 11:919-930,1996.
Lance P, Leu R: Colonic oligosaccharide structures deduced from lectin-binding studies before and after desialylation. Hum Pathol 22:307-312, 1991.
Desilets DJ, Davis KE, Nair PP, et al: Lectin binding to human colonocytes is predictive of colonic neoplasia. Am. J. Gastroenterol. 94: 744-750, 1999.
Ryder SD, Smith JA, Rhodes EGH, et al: Proliferative responses of HT29 and Caco2 human colorectal cancer cells to a panel of lectins. Gastroenterology 106:85-93, 1994.
Kellokumpu IH, Aandersoon LC, Kellokumpu SJ: Detection of colorectal neoplasia with Peanut-Agglutinin, PNA)-reactive carbohydrate structures in rectal mucus. Int J Cancer, Pred. Oncol., 74:648-653, 1997.
Sams JS, Lynch HT, Burt RW, et al: Abnormalities in lectin histochemistry in familial polyposis coli and hereditary nonpolyposis colorectal cancer. Cancer 66:502-508,1990.
Boland CR, Roberts JA: Quantitation of lectin binding sites in human colon mucins by use of peanut and wheat germ agglutinins. J Histochem Cytochem 36:1305-1307,1988.
Drackenberg CB, Papadimitriou JC: Aberrant pattern of lectin binding in low and high grade prostatic intraepithelial neoplasia. Cancer 75:2539-2544, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 265
EP 271
PG 7
ER
PT J
AU Demirkan, CN
Colakoglu, N
Duzcan, E
AF Demirkan, Calli Nese
Colakoglu, Nagihan
Duzcan, Ender
TI Value of p53 Protein in Biological Behavior of Basal Cell Carcinoma and in Normal Epithelia Adjacent to Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ageing; basal cell carcinoma; p53 protein
ID ageing; basal cell carcinoma; p53 protein
AB Mutations in p53 gene are the most frequent gene alterations in human cancer. In this study, we have used the monoclonal antibody (DO7) to evaluate the role of the p53 gene mutation in the progression of basal cell carcinomas towards invasion. We tested the positivity for p53 protein in tumor cells in six cases of basosquamous cell carcinoma (BSCC), in twelve cases of infiltrative basal cell carcinoma (IBCC) and twenty-four cases of non-infiltrative basal cell carcinoma (NIBCC) in order to evaluate its potential prognostic significance. We also tested the expression of p53 protein in normal epithelia adjacent to carcinomas in order to determine its role in tumor progression. p53 protein staining with some peripheral accentuation was identified in 42,9% of all groups. No correlation was found between the immunreactivity of p53 protein and recurrence, pattern of tumor, diameter of the tumors and sex. However, there were statistically significant differences in positivity of p53 protein in normal epithelia adjacent to carcinomas and age of patients (t value: 2,21; p: 0,034). Results of the study suggest that the increasein p53 mutation frequency of morphologically normal epidermis was related to age and was independent of the degree of differentiation of BCC.
C1 [Demirkan, Calli Nese] Pamukkale University, Department of Pathology, 269 sok. No: 46-8 Ucyol, 35280 Izmir, Turkey.
[Colakoglu, Nagihan] Pamukkale University, Department of Pathology, 269 sok. No: 46-8 Ucyol, 35280 Izmir, Turkey.
[Duzcan, Ender] Pamukkale University, Department of Pathology, 269 sok. No: 46-8 Ucyol, 35280 Izmir, Turkey.
RP Demirkan, CN (reprint author), Pamukkale University, Department of Pathology, 35280 Izmir, Turkey.
EM nesefahir@hotmail.com
CR Barret TL, Smith KJ, Hodge JJ, et al: Immunohistochemical nuclear staining for p53, PCNA and Ki-67 in different histologic variants of basal cell carcinoma. J Am Acad Dermatol 37:430-437, 1997.
D’Errico M, Calcagnile AS, Corona R, et al: p53 Mutations and chromosome instability in basal cell carcinoma s developed at an early or late age. Cancer Res 57:747-752, 1997.
De Rosa G, Staibano S, Barra E, et al: p53 Protein in aggressive and non-aggressive basal cell carcinoma. J Cutan Pathol 20:429-434, 1993.
Dixon AY, Lee SH, McGregor DH: Histologic evolution of basal cell carcinoma recurrence. Am J Dermatopathol 13:241,1991.
Gunterson BA, Anbazhagan R, Warren W: Expression of p53 in premalignant and malignant squamous epithelium. Oncogene 6:1785-1789, 1986.
Helander SD, Peters MS, Pittelkow MR: Expression of p53 protein in benign and malignant epidermal conditions. J Am Acad Dermatol 29:741-748, 1993.
Jones MS, Helm KF, Maloney ME: The immunohistochemical characteristics of the basosquamous cell carcinoma. Dermatol Surg 23:181-184, 1997.
Kirkham N: Tumors and cysts of the epidermis. In: Lever’s histophology of the skin, Eds: Elder D, Elenistas R, Jaworsky C, Johnson B). 1997, pp 719-731. Philadelphia New York, Lippincott- Raven.
Liang SB, Ohtsuki Y, Furihata M, et al: Sun-exposure and ageing- dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer. Virchows Arch 434:193-199, 1999
Matsumura Y, Nishigor C, Yagi T, et al: Characterization of p53 gene mutations in basal-cell carcinomas: comparison between sun-exposed and less- exposed skin areas. Int J Cancer 65:778- 780, 1996.
Onodera H, Nakamura S, Sugai T: Cell proliferation and p53 protein expressions in cutaneous epithelial neoplasms. Am J Dermatopathol 18:580-588, 1996.
Ro YS, Cooper PN, Lee JA, et al: p53 protein expression in benign and malignant skin tumours. Br J Dermatol 128:237-241, 1993.
Sexton M, Jones DB, Maloney ME: Histologic pattern analysis of basal cell carcinoma. J Am Acad Dermatol 23:1118-1126, 1990.
Shea CR, McNutt NS, Volkenandt M, et al: Overexpression of p53 protein in basal cell carcinomas in human skin. Am J Pothol 141:25, 1992.
Urano Y, Asano T, Yoshimoto K, et al: Frequent p53 accumulation in the chronically sun-exposed epidermis and clonal expansion of p53 mutant cells in the epidermis adjacent to basal cell carcinoma. J Invest Dermatol 104:928-932, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 272
EP 274
PG 3
ER
PT J
AU Nasierowska-Guttmejer, A
Trzeciak, L
Nowacki, PM
Ostrowski, J
AF Nasierowska-Guttmejer, Anna
Trzeciak, Lech
Nowacki, P Marek
Ostrowski, Jerzy
TI p53 Protein Accumulation and p53 Gene Mutation in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53 protein; p53 gene; molecular biology; immunohistochemical studies; colorectal cancer
ID p53 protein; p53 gene; molecular biology; immunohistochemical studies; colorectal cancer
AB Comparison of immunohistochemical methods for detection of protein p53 accumulation and molecular techniques for analysis p53 gene mutation in colorectal cancer is presented. Thirty eight patients were included: all underwent surgery without preoperative treatment. Sex of patients, tumor localisa-tion, macro and microscopic type of cancer and staging according to Astler-Coller and Jass classifications were evaluated. Protein p53 accumulation was detected by the streptavidin-biotin method using DO-7 (Dako) antibody. The number of cells stained were classified semiquanititatively according to a scoring system: (–)no positive cells, (+) : 10-30% positive cells, (++) : 40-70% positive cells, (+++) : >70% positive cells. For all cancer samples, exons 5 to 9 of p53 gene were amplified from isolated genomic DNA. PCR products were subjected to single standed conformational polymorphism analysis. All product were also directly sequenced on ABI PRISM 377 apparatus using fluorescent dideoxyterminators chemistry. The protein p53 accumulation was detected in 53% (20/38), whereas p53 gene mutation was seen in 55% (21/38). Among them, 15 patients (39%) with overexpression showed mutation in exon 5-8 gene p53. Discrepancies between results were noted in 29%. In conclusion, the necessity of both methods – immunohistochemical and molecular – is indicated for the objective evaluation of functional and structural status of p53 gene and protein.
C1 [Nasierowska-Guttmejer, Anna] Medical Center for Postgraduate Education, and Maria Sk³odowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Pathology, Roentgena str. 5, 02-971 Warsaw, Poland.
[Trzeciak, Lech] Medical Center for Postgraduate Education and Maria Sk³odowska-Curie Memorial Cancer Center and Institute of Oncology, Department of GastroenterologyWarsaw, Poland.
[Nowacki, P Marek] Maria-Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Colorectal CancerWarsaw, Poland.
[Ostrowski, Jerzy] Medical Center for Postgraduate Education and Maria Sk³odowska-Curie Memorial Cancer Center and Institute of Oncology, Department of GastroenterologyWarsaw, Poland.
RP Nasierowska-Guttmejer, A (reprint author), Medical Center for Postgraduate Education, and Maria Sk³odowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Pathology, 02-971 Warsaw, Poland.
CR Agarwall ML, Taylor WR, Chernov MV, et al: The p53 network. J Biol Chem 273:1-4, 1998.
Bass IO, Mulder JWR, Offerhaus GJA, et al: An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 172:5-12, 1994.
Bertorelle R, Esposito G, Del Mistro A, et al: Association of p53 gene and protein alterations with metastases in colorectal cancer. Am J Surg Pathol 19:463-471, 1995.
Borresen DA, Lothe RA, Meling GI, et al: TP53 and long-term prognosis in colorectal cancer: mutation in the L3 zinc-binding domain predict poor survival. Clin Cancer Res 4:203-210, 1998.
Bosari S and Viale G: The clinical significance of p53 aberrations in human tumors. Virchows Arch 427:229-241, 1995.
Caldes T, Iniesta P, Vega FJ, et al: Comparative survival analysis of p53 gene mutation and protein accumulation in colorectal cancer. Oncology 55:249-257, 1998.
Cripps KJ, Purdie CA, Carder PJ, et al: A study of stabilisation of p53 protein versus point mutation in colorectal carcinoma. Oncogene 9:2739-2743, 1994.
Dix B, Robbins P, Corello S, et al: Comparison of p53 gene mutation and protein overexpression in colorectal cancer. Br J Cancer 70:585-590, 1994.
El-Deiry WS, Kern SE, Pietenpol JA, et al: Definition of a consensus binding site for p53. Nature Genet 1:45-49, 1992.
Goh HS, Yao J and Smith DR: p53 point mutation and survival in colorectal cancer patients. Cancer Res 55:5217-5221, 1995.
Greenblatt MS, Bennett WP, Hollstein M, et al: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855-4878, 1994.
Hall PA and Lane DP: p53 in tumor pathology: can we trust immunohistochemistry?-revisited! J Pathol 172:1-4, 1994.
Hamelin R, Laurent PP and Olschwang S: Association of p53 mutations with short survival in colorectal cancer. Gastroenterology 106:42-48, 1994.
Hasegawa H, Ueda M, Furukawa K, et al: p53 gene mutations in early colorectal carcinoma. de novo vs adenoma-carcinoma sequence. Int J Cancer 64:47-51, 1995.
Hollstein M, Sidransky D, Vogelstein B, et al: p53 mutations in human cancers. Science 253:49-53,1991.
Jass JR, Love SB, Northover JMA: A new classification of rectal cancer. Lancet i: 1303-1306, 1987.
Jass J, Sobin WH: Histological typing of intestinal tumours. World Health Organisation. International Histological Classification of Tumours. Springer-Verlag, 1989.
Kawasaki Y, Monden T, Morimoto H, et al: Immunohistochemical study of p53 expression in microwave-fixed, parrafinembedded sections of colorectal carcinoma and adenoma. Am J Clin Pathol 97:244-249, 1992.
Lewine AJ: p53 , the cellular gatekeeper for growth and division. Cell 88: 23-331, 1997.
Locker J: Tumor suppressor genes and the practice of surgical pathology. Hum Pathol 4:359-361, 1995.
Nasierowska-Guttmejer A, Roszkowska-Purska K, Gil M, et al: Protein p53 accumulation and proliferative activity in adenomas and early carcinoma of the colorectum. Gastroenterologia Polska 5:341-347, 1998.
Oren M, Maltzman W, Levine AJ: Posttranslational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol 1:101-110, 1981.
Prives C, Hall PA: The p53 pathway. J Pathol 187:112-126, 1999.
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Smith DR, Ji C-Y, Goh H-S: Prognostic significance of p53 overexpression and mutation in colorectal adenocarcinomas. Br J Cancer 74:216-223, 1996.
Starzynska T, Bromley M, Marlicz K, et al: Accumulation of p53 in relation to long-term prognosis in colorectal carcinoma. Europ J Gastroent Hepatol, 9:183-186, 1997.
Takeda A, Nakajima K, Shimada H, et al: Significance of serum p53 antibody detection on chemosensitivity assay in human colorectal cancer. J Surg. Oncol 71:112-116, 1999.
Valentini AM, Pirrelli M, Caruso ML: p53 protein in colorectal cancer: clinicopathological correlation and prognosis significance. J Exp Clin Cancer Res 14:139-144, 1995.
Yandell DW, Thor AD: p53 analysis in diagnostic pathology. Biologic implications and possible clinical applications. Diag Molec Pathol 2:1-3, 1993.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 275
EP 279
PG 5
ER
PT J
AU Kvell, K
Balogh, P
Nemeth, P
AF Kvell, Krisztian
Balogh, Peter
Nemeth, Peter
TI Fine-tuning the EBV+ hu-PBL-SCID Xenogeneic Chimera Model Using InVivo Superinfection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE SCID mice; lymphoproliferative disease; EBV superinfection; B cell proliferation
ID SCID mice; lymphoproliferative disease; EBV superinfection; B cell proliferation
AB Our purpose was to establish a reproducible xenogeneic chimera model to observe tumors similar to the well-known human posttransplant lymphoproliferative disease (LPD). First we followed the original protocol injecting Epstein-Barr virus positive (EBV+) human peripheral blood lymphocytes (PBL) intraperitoneally into immunodeficient (SCID) mice. Human cells showed T cell phenotype in majority one week after the transfer, whereas one month later a shift towards B cell phenotype was evident according to immunohistochemical and flow cytometric analysis. At this stage the intraperitoneal mass of cells suggested a biologically malignant behaviour infiltrating the liver and the spleen of the host animal. Immunohistochemistry indicated proliferating human lymphatic cells expressing EBV associated proteins and characteristic patterns of invasion within the affected organs. Eventually LPD was lethal to the host animals in 46-67 days. However, the microscopic appearance of experimental LPD was different from the human haemopoietic malignancies: the basic structures of lymphatic organs were preserved and the human T and B cells repopulated the normally T and B dependent areas in mice. The phenotypes of the proliferating cells were human and characteristic for the mature T- and B-lymphocytes. No dominant clone developed during in vitroculturing of the biologically invasive mass of cells removed from the tumor-bearing mice. The results of microscopical, immunological, and flow cytometrical analysis suggested a mature but uncontrolled proliferation of human lymphocytes in SCID mice. The original method for the induction of post-transplant LPD in SCID mice was modified in our further experiments to standardise the experimental technique increasing the efficiency of B cell proliferation and the reducing the number of unspecific factors. Subsequent in vivo EBV superinfection was carried out after the intraperitoneal transfer of a reduced quantity of human PBL from different donors. The same disease developed in our modified chimera model as by the use of original protocol except for some valuable differences. All hosts developed LPD regardless the significantly reduced amount of transplanted PBL and it was lethal in a shorter period of time (41-43 days) compared to the original model. The decreased quantity of transplanted human lymphatic cells was formerly insufficient using the original protocol. Therefore this modified and standardised protocol can lead to a more predictable and reproducible model allowing us to examine fine details of posttransplant lympho-proliferative disease.
C1 [Kvell, Krisztian] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Balogh, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
RP Nemeth, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM pnemeth@apacs.pote.hu
CR Amadori A, Veronesi A, Coppola V, et al: The hu-PBL-SCID mouse in human lymphocyte function and lymphomagenesis studies: achievements and caveats. Seminars in Immunology 8- 4:249-254, 1996.
Belagyi J: Medical biometry – an introduction. pp.21, 1999.
Boyle TJ, Tamburini M, Berend KR, et al: Human B cell lymphoma in severe combined immunodeficient mice after active infection with Epstein-Barr virus. Surgery 112-2:378-386, 1992.
Carlsson R, Martensson C, Kalliomaki S, et al: Human peripheral blood lymphocytes transplanted into SCID mice reconstitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies. The Journal Of immunology 148:1065-1071, 1992.
Fuzzati-Armento M-T, Duchosal MA: hu-PBL-SCID mice: an in vivo model of Epstein-Barr virus-dependent lymphoproliferative disease. Histology and Histopathology 13:155-168, 1998.
Gleick J: Chaos – the birth of a new science pp.305-335, 1987.
Hanto DW, Sakamoto K, Purtilo DT, et al: The Epstien-Barr virus in the pathogenesis of posttransplant lymphoproliferative disorders – clinical, pathologic and virologic correlation. Surgery 90:204-213, 1981.
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Lacerda JF, Ladanyi M, Jagiello C, et al: Administration of rabbit anti-asialo GM1 antiserum facilitates the development of human Epstein-Barr virus-induced lymphoproliferations in xenografted C.B.-17 scid/scid mice. Transplantation 61-3:492- 497, 1996.
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Murphy WJ, Taub DD, Longo DL: The hu-PBL-SCID mouse as a means to examine human immune function in vivo. Seminars in Immunology 8-4:233-242, 1996.
Nakamine H, Okano M, Taguchi Y, et al: Hematopathologic features of Epstein-Barr virus-induced human B-lymphoproliferation in mice with severe combined immune deficiency. Laboratory Investigation 65-4:389-399, 1991.
Picchio G, Kobayashi R, Kirven M, et al: Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. Cancer Research 52:2468-2477, 1992.
Thorley-Lawson DA, Babcock GJ: A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Science 65-14:1433-1453, 1999.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 280
EP 286
PG 7
ER
PT J
AU Orosz, Zs
Rohonyi, B
Luksander, A
Szanto, J
AF Orosz, Zsolt
Rohonyi, Bela
Luksander, Antal
Szanto, Janos
TI Pleomorphic Liposarcoma of a Young Woman Following Radiotherapy for Epithelioid Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE epithelioid sarcoma; pleomorphic liposarcoma; postirradiation sarcoma
ID epithelioid sarcoma; pleomorphic liposarcoma; postirradiation sarcoma
AB A case of a metachronous epithelioid sarcoma and pleomorphic liposarcoma in a young woman is described. The first tumor was an epithelioid sarcoma (ES) with focal rhabdoid features localised in the left calf while the second lesion developed seven years later in the same region was diagnosed as pleomorphic liposarcoma resembling myxofibrosarcoma (''myxoid variant of malignant fibrous histiocytoma'') predominantly composed of moderately differentiated spindle cells. Multiple foci of uni- and plurivacuolated lipoblasts were seen. Following the resection of ES the patient received 57 Gy radiation to the region, therefore we regarded the second tumor as a radiation induced liposarcoma. A further interesting feature of this case is that the development of pleomorphic liposarcoma preceded by 6 months the solitary right parabronchial metastasis of ES and after 4 months of metastasectomy a third tumor developed at the site of the first lesion. This tumor showed dedifferentiation toward pleomorphic malignant fibrous histiocytoma. Our case represents a unique case of postirradiation liposarcoma developed on the base of ES.
C1 [Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Rohonyi, Bela] Erzsebet Hospital, Department of PathologySopron, Hungary.
[Luksander, Antal] Erzsebet Hospital, Department of SurgerySopron, Hungary.
[Szanto, Janos] University of Debrecen, Department of OncologyDebrecen, Hungary.
RP Orosz, Zs (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
EM zso@oncol.hu
CR Amendola BE, Amendola MA, McClatchey KD, et al: Radiation- associated sarcoma: a review of 23 patients with postradiation sarcoma over 50 year period. Am J Clin Oncol 12:411- 415, 1989.
Arber DA, Kandalaft PL, Mehta P, et al: Vimentin-negative epithelioid sarcoma. The value of an immunohistochemical panel that includes CD34. Am J Surg Pathol 17:302-307, 1993.
Cahan WG, Woodward HQ, Mehta P, et al: Vimentin-negative epithelioid sarcoma. The value of an immunohistochemical panel that includes CD34. Am J Surg Pathol 17:302-307, 1993.
Chase DR, Enzinger FM: Epithelioid sarcoma: diagnosis, prognostic indicators and treatment. Am J Surg Pathol 9:241-263, 1985.
Enzinger FM, Weiss SW, et al: Soft tissue tumors. St. Louis: Mosby, 1995.
Evans HL, Baer SC: Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases. Semin Diagn Pathol 10:286- 91; 1993.
Fletcher CDM: Das histologische Erscheinungsbild bei Lokalrezidiven von Weichgewebssarkomen. Pathologe 15:196- 200, 1994.
Guillou L, Wadden C, Coindre J-M, et al: “Proximal-type” epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Am J Surg Pathol 21:130-146, 1997.
Halling AC, Wollan PC, Pritchard DJ, et al: Epithelioid sarcoma: a clinicopathologic review of 55 cases. Mayo Clin Proc 71:636-642, 1996
Jacobsen GK, Mellemgard A, Engelholm SA, et al: Increased incidence of sarcoma in patients treated for testicular seminoma. Eur J Cancer 29A:664-669, 1993.
Kaldor JM, Day NE, Band P, et al: Second malignancies following testicular cancer, ovarian cancer and Hodgkin’s disease: an international collaborative study among cancer registries. Int J Cancer 39:571-585, 1987.
Laskin WB, Silverman TA, Enzinger FM: Postradiation soft tissue sarcomas. An analysis of 53 cases. Cancer 62:2330-2340, 1988.
van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, et al: Second cancer risk following testicular cancer: a follow-up of 1909 patients. J Clin Oncol 11:415-424; 1993.
Mark RJ, Poen J, Tran LM, et al: Postirradiation sarcomas. A single-institution study and review of the literature. Cancer 73:2653-2662, 1994
Mirra JM, Kessler S, Bhuta S, et al: The fibroma-like variant of epithelioid sarcoma. Cancer 69:1382-95; 1992.
Wiklund TA, Blomqvist CP, Raty J, et al: Postirradiation sarcoma. Analysis of a nation-wide cancer registry material. Cancer 68:524-531; 1991.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 287
EP 291
PG 5
ER
PT J
AU Arato, G
Fulop, V
Degrell, P
Szigetvari, I
AF Arato, Gabriella
Fulop, Vilmos
Degrell, Peter
Szigetvari, Ivan
TI Placental Site Trophoblastic Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE placental trophoblastic tumor; choriocarcinoma; immunohistology; intermediate trophoblast
ID placental trophoblastic tumor; choriocarcinoma; immunohistology; intermediate trophoblast
AB Placental site trophoblastic tumor (PSTT) is the rarest disease of the gestational trophoblast. Our two cases will be interesting not only because of the rarity of the disease, but because both were recognized before operation. Since the tumor cells are lined up tightly side by side, this disease must be distinguished primarily from tumors of epithelial origin. The authors highlight that the diagnosis should rely on intense hPL-positivity as well as the ultrastructural image of the tumor. In histologically equivocal cases, the determination of hPL, hCG, and MIB-1 immunologic markers can be recommended as routinely performed morphological examinations. Serum hCG monitoring is recommended to follow the evolution of the tumor.
C1 [Arato, Gabriella] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Szabolcs u. 35., H-1135 Budapest, Hungary.
[Fulop, Vilmos] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Degrell, Peter] County Hospital of Borsod-Abauj-Zemplen, Department of PathologyMiskolc, Hungary.
[Szigetvari, Ivan] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
RP Arato, G (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1135 Budapest, Hungary.
CR Biran H, Dgani R, Wasswemwn JD, et al: Pneumothorax following induction chemotherapy: a case report. Ann Oncol 3:297-300, 1992.
Denny LA, Dehaeck K, Neviz J, et al: Placental site trophoblastic tumor: three case report and literature review. Gynecol Oncol 59:300-303, 1995.
Fukunaga M, Ushigome S: Malignant trophoblastic tumor. Hum Pathol 24:1098-1106, 1993.
Hopkins MP, et al: Malignant placental site trophoblastic tumor associated with placental abruption, fetal distress and elevated CA-125. Gynecol Oncol 47:267-271, 1992.
Kashimura M, Kashimura Y, Oikawa K, et al: Placental site trophoblastic tumor: immunohistochemical and nuclear DNA study. Gynecol Oncol 38:262-267, 1990.
Kurman RJ: The morphology, biology and pathology of intermediate trophoblast – a look to the present. Human Pathol 22:847-855, 1991.
Kurman RJ, Scully RE, Norris HJ: Trophoblastic pseudotumor of the uterus. An exaggerated form of “syncytial endometritis” simulating a malignant tumor. Cancer 38:1214-1226, 1976.
Larsen LG, Theilade K, Skibsted L, et al: Malignant placental site trophoblastic tumor. A case report and review of the literature. APMIS Suppl. 23:138-145, 1991.
Marchand F: Uber die sogenannten ”decidualen” geschwulste im Anschloss an normale Gebart, Abort, Blasenmole, und Extrauterin Schwangerschaft. Monatsschr Geburtshilfe Gynaekol 1:419, 1985.
Orell JM, Sanders DSA: A particularly aggressive placental site trophoblastic tumor. Histopathol 18:559-561, 1991.
Remadi S, Lifschitz-Mercer B, Ben-Hur H, et al: Metastasizing placental site trophoblastic tumor: Immunohistochemical and DNA analysis. Arch Gynecol 259:97-103, 1997.
Shin IM, Kurman RJ: Expression of melanoma cell adhesin molecule in intermediate trophoblast. Lab Invest 75.
Vardar MA, Altintas A: Placental site trophoblastic tumor. Principles of diagnosis, clinical behaviour and treatment. Eur J Gynecol 16:290-295, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 292
EP 294
PG 3
ER
PT J
AU Rethy, AL
Kalmanchey, R
Klujber, V
Koos, R
Fekete, Gy
AF Rethy, A Lajos
Kalmanchey, Rozalia
Klujber, Valeria
Koos, Rozalia
Fekete, Gyorgy
TI Acid Sphingomyelinase Deficiency in Beckwith-Wiedemann Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Beckwith-Wiedemann syndrome; acidic sphingomyelinase deficiency; embryonal rhabdomyosarcoma; simultaneous occurrence
ID Beckwith-Wiedemann syndrome; acidic sphingomyelinase deficiency; embryonal rhabdomyosarcoma; simultaneous occurrence
AB We report the association of Beckwith-Wiedemann syndrome (BWS) and a residual acid sphingomyelinase (ASM) activity of about 35% in a 23 months old Hungarian boy. Besides the classical triad of exomphalos, macroglossia and gigantism some other BWS-related features: polyhydramnios (known from the praenatal history), hemihypertrophy, craniofacial dysmorphy, a mild mental retardation, bilaterally undescended testes, cardiac anomalies and a terminally developed, fatal embryonal rhabdomyosarcoma were present in the patient. The decreased activity of the ASM was measured in the patient’s skin fibroblasts. This result, with hepatomegaly, mental retardation, feeding problems, a failure to thrive and muscle-hypotony, partially resembled the ASM-deficient forms of Niemann-Pick disease (NPD). Morphological analysis of the bone-marrow cells gave normal results. There was no chromosomal alteration found by conventional karyotyping of the patient’s lymphocytes.BWS-associated genes as well as the human ASM gene (SMPD1) are all located at 11p15. DNA-studies by region specific markers as well as mutational analysis for the most common NPD-mutations are planned in the future. This is the first report on the simultaneous occurrence of BWS and ASM-deficiency.
C1 [Rethy, A Lajos] Bethesda Children's Hospital of the Hungarian Reformed Church, Bethesda u. 3., H-1146 Budapest, Hungary.
[Kalmanchey, Rozalia] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Klujber, Valeria] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Koos, Rozalia] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Fekete, Gyorgy] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
RP Rethy, AL (reprint author), Bethesda Children's Hospital of the Hungarian Reformed Church, H-1146 Budapest, Hungary.
EM retlaj@yahoo.com
CR Eliot M, Maher ER: Beckwith-Wiedemann syndrome. J Med Genet 31:560-564, 1994.
Sotelo-Avila C, Gonzalez-Crussi F, Fowler JW: Complete and incomplete forms of Beckwith-Wiedemann syndrome: Their oncogenic potential. J Pediatr 96:47-50, 1980.
Wiedemann HR: Tumors and hemihypertrophy associated with Wiedemann-Beckwith syndrome. Eur J Pediatr 414:429, 1983.
Reik W, Maher ER: Imprinting in clusters: lessons from Beckwith- Wiedemann syndrome: Trends Genet 13:330-334, 1997.
Feinberg AP: Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res 59, Suppl):1743s-1746s, 1999.
Schuchman, EH, Desnick RJ: Niemann-Pick disease types A and B: acid sphingomyelinase deficiencies. In: Scriver C.R., Beaudet A.L., Sly W.S., Valle D, eds.): The metabolic and molecular basis of inherited disease, 7th ed. McGraw-Hill, New York, 1995. pp 2601-2624.
Gaudray P, Carle GF, Gerhard DS, et al: Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998. Nice, France, May 2-5, 1998. Cytogenet Cell Genet 86:167-186, 1999.
Neri G, Marini R, Cappa M, et al: Simpson-Golabi-Behmel syndrome: an X-linked encephalo-trophoschisis syndrome. Am J Med Genet 30:287-299, 1988.
Grundy RG, Pritchard J, Baraitser M, et al: Perlman and Wiedemann-Beckwith syndromes: two distinct conditions associated with Wilms’ tumour. Eur J Pediatr 151:895-898, 1992.
Wiedemann HR, Grosse KR, Dibbern H: An atlas of characteristic syndromes. Wolfe Medical Publications, London, 1985.
Cohen MM, Jr: A comprehensive and critical assessment of overgrowth and overgrowth syndromes. Adv Hum Genet 29:22-25, 1992.
Mannens M, Alders M, Redeker B, et al: Positional cloning of genes involved in the Beckwith-Wiedemann syndrome, hemihypertrophy, and associated childhood tumors. Med Pediatr Oncol 27:490-494, 1996.
Bliek J, Alders M, Ryan A, et al: The Beckwith-Wiedemann syndrome: entrance to genes involved in growth regulation. Abstract of the 6th International Workshop on Human Chromosome 11, Nice, France, 1998. URL: http://wwwiag.unice.fr/ workshop/SCW11-6-Abstracts.html
Redeker E, Alders M. Hoovers J, et al: Physical mapping of 3 candidate tumour suppressor genes relative to BWS associated chromosomal breakpoints at 11 p 15.3. Cytogenet Cell Genet 68:222-225, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 295
EP 297
PG 3
ER
PT J
AU Rethy, AL
AF Rethy, A Lajos
TI Growth Regulation, Acid Sphingomyelinase Gene and Genomic Imprinting: Lessons from an Experiment of Nature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE acid shingomyelinase; ceramide; Beckwith-Wiedemann Syndrome; growth regulation; apoptosis; conflict theory; imprinting in clusters
ID acid shingomyelinase; ceramide; Beckwith-Wiedemann Syndrome; growth regulation; apoptosis; conflict theory; imprinting in clusters
AB The author investigated the possible role of acid sphingomyelinase (ASM) gene (SMPD1) in the regulation of growth, in connection with an experiment of nature. The association of a decreased ASM activity and an overgrowth disorder, Beckwith-Wiedemann Syndrome (BWS) with hemihypertrophy has been described at a 23 months old boy in a recent case report (Rethy et al, in this issue). ASM catalyses the production of ceramide, a key molecule of apoptosis, from sphingomyelin. Based on these data it is suggested that the ASM gene (SMPD1) can suppress/counterbalance the anti-apoptotic effects of BWSrelated growth-promoters, like IGF-II, under normal circumstances. Recent literary data support this view. ASM deficient lymphoblasts derived from patients with Niemann-Pick disease (NPD) fail to undergo apoptosis in response to external signals and Fas cross-linking. BWS-related genes are considered to be regulated by genomic imprinting. Therefore the author compared some characteristics of both SMPD1 and imprinted genes. The analyzed features of SMPD1 gene (few and small introns, Alu 1 repeat element, CC-rich regulatory region, alternative splicing) are characteristic to imprinted genes. Hemihypertrophy, mentioned in the referred BWS-case, is distinctive to the involvement of the maternal allele of the second BWS chromosomal region (BWSCR2) at 11p15.3. The SMPDI gene has been localized just distal to the B05 breakpoint of BWSCR2. Furthermore, in BWS-associated tumors, the loss of heterozygosity (LOH) found on 11p15 was always maternal. Thus, in the case referred to with ASM deficiency the maternal allele has certainly been effected. These conclusions are in accordance with the 'cluster-model of imprinting' as well as with the conflict theory of imprinting. Taken together, the above mentioned clinical and experimental data suggest that SMPD1, most likely at 11p15.4, is an imprinted, maternally expressed, BWS- and apoptosis-related growth suppressor gene. Further studies are necessary to prove this hypothesis.
C1 [Rethy, A Lajos] Independent Research Group for Genetics -and Immunology, HRC-Bethesda Children's Hospital, Bethesda u. 3., 1146 Budapest, Hungary.
RP Rethy, AL (reprint author), Independent Research Group for Genetics -and Immunology, 1146 Budapest, Hungary.
EM retlaj@yahoo.com
CR Rehthy LA, Kalmanchey R, Khaber V, et al: Acid Sphingomyelinase Deficiency in Beckwith-Wiedemann Syndrome. Pathol Oncol Res 6:295-297, 2000.
Haimovitz-Friedman A, Kolesnick RN, Fuks Z: Ceramide signaling in apoptosis. Brit Med Bullet 53:539.553, 1997.
Gaudray P, Carle GF, Gerhard DS, et al: Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998. Cytogenet Cell Genet 86:168-186m, 1999.
Mannens M, Alders M, Redeker B, et al: Positional cloning of genes involved in the Beckwith-Wiedemann syndrome, hemihypertrophy, and associated childhood tumors. Med Pediatr Oncol 27:490-94, 1996. S. Reik W, Maher ER: Imprinting in clusters: lessns from Beckwith-Wiedemann syndrome. Trends Genet 13:330-334, 1997. 6. Feinberg AP: Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res 59, Suppl:, 1743s-1746s. 1999. 7. Moore T, Haig D: Genomic imprinting in mammalian development: A parental lug of war. Trends Genet 7:45-49, 1991. 8. http://www.ncbi.nlm.nih.gov/pubmed/ 9. Hurst DL, McVean G, MooreT: Imprinted genes have few and small introns. Nat Genet 12:234-237, 1996. 10. Mannens M, Hoovers JM, Redeker E, et al: Parental imprinting of hum. chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia. Eur J Hum Genet 2:3-23, 1994. 11. Santana P, Pena LA, Haimovitz-Friedman A, et al: Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 86:189-199, 1996. 12. De Maria R, Rippo MR, Schucman EH, et al : Acidic sphingomyelinase, ASM, is necessary for far-induced GD3 ganglioside accumulation and efficient apoptosis of lymphoid cells. J Exp Med. 187:897-902, 1998. 13. Cock JG. Tepper AD, de Vries E, er al: CD95 Was/APO-II induces ceramide formation and apoptosis in the absence of a functional mid sphingomyelinase. J Biol Chem 273:7560-7565, 1998. 14. Separovic D, Pink JJ, Oleinick NA, et al: Nicmann-Pick human lymphoblasts are resonant to phthatheyanine 4-photodynamic therapy-induced apoposis. Biochem Biophys Res Common 258:506-512, 1999. 15. Malisan F, Testi R: Lipid signaling in CD95-mediated apoptosis. FEBS Lett 452:100-101 1999. 16. McKusick, VA: Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore: Johns Hopkins University Press. 1998, 12th edition). 17. Schuchman EH, Desnick RJ: Niemann-Pick disease types A and B: acid sphingomyelinase deficiencies. In: Striver C.R.. Braider Sly WS., Valle D, eds.): The metabolic and molecular basis of inherited disease. 7th ed. McGraw-Hill, New York, 1995. pp 2601-2624. 18. Weil D, D'Alessio M, Ramirez F et al: A base substitution in the exon of a oullagen gene causes alternative splicing and generates a structurally abnormal polypeptide in a patient with Ehlers-Danlas syndrome type VII. EMBO J 8:1705-1710, 1989. 19. Neumann B, Kubicka P, Barlow: Characteristics of imprinted genes. Nat Genet 9:12-13, 1995. 20. Ellsworth DL, Hewett-Emmett D, Li WH: Evolution of base composition in the insulin and insulin-like growth factor genes. Mol Biol Evol 11:875-885, 1994. 21. Duret L, Mouchiroud D, Gautier C: Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC richisochores. J Mol Evol 40:308-3M, 1995. 22. Nielsen FC, Ostergaard IL, Nielsen J, et al: Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway. Nature 377:358-362,1995. 23. Alders M, Bliek J, Redeker B, et al: Cloning of candidate genes involved in the Beckwith-Wiedemann syndrome and childhood tumors. Med Pediatr Oncol 27:495-497, 1996. 24. Redeker E, Alders M, Hoovers J, at al: Physical mapping of 3 candidate tumouniuppressor genes relative to BWS associated chromosomal breakpoints at 1 1p 15.3. Cytogenet Cell Genet 68:222-225, 1995. 25. Lee MP, Feinberg AP: Genomic imprinting of a human apoptosis gene homologue, TSSC3. Cancer Res 58;1052-1056, 1998.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 298
EP 300
PG 3
ER
PT J
AU Loreto, FM
De Martinis, M
Corsi, PM
Modesti, M
Ginaldi, L
AF Loreto, Francesca Maria
De Martinis, Massimo
Corsi, Pia Maria
Modesti, Marco
Ginaldi, Lia
TI Coagulation and Cancer: Implications for Diagnosis and Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE thrombosis; malignancy; haemostasis; oncology; therapy
ID thrombosis; malignancy; haemostasis; oncology; therapy
AB Coagulation disorders are a common problem in neoplastic patients and many factors contribute to increase the risk of thromboembolic events in these patients. An hypercoagulable state is induced by malignant cells interacting directly with hemostatic system and activating the coagulation cascade. More sensitive tests to assess an hypercoagulable state in cancer patients have been developed; even though these tests are always altered in cancer patients, none of them possess a clinical significance in terms of predictive value for the occurence of thromboembolism and disease prognosis in the individual patient. The most frequent thromboembolic complications in cancer patients are deep vein thrombosis of the lower extremities and pulmonary embolism; therefore, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura or haemolytic uremic syndrome are special manifestations of neoplastic disease. Diagnosis of idiopathic deep vein thrombosis, in the absence of other risk factors, could indicate the presence of occult malignant disease; however, the need for an extensive work-up to detect malignancy is still controversial. Neoplastic patients showing a thromboembolic event should be treated with unfractioned heparin or, alternatively, with low molecular weight heparins. In order to prevent recurrence, the administration of heparin should be associated and followed by an oral anticoagulant drug. In recent years new approaches in anti-aggregation therapy have been studied, such as COX-inhibitors, cicaprost and ReoPro; further studies are needed to determine the usefulness of these molecules in treatment of malignancies.
C1 [Loreto, Francesca Maria] University of L'Aquila, Department of Internal Medicine and Public Health, Via San Sisto 22/E, 67100 L'Aquila, Italy.
[De Martinis, Massimo] University of L'Aquila, Department of Internal Medicine and Public Health, Via San Sisto 22/E, 67100 L'Aquila, Italy.
[Corsi, Pia Maria] University of L'Aquila, Department of Internal Medicine and Public Health, Via San Sisto 22/E, 67100 L'Aquila, Italy.
[Modesti, Marco] University of L'Aquila, Department of Internal Medicine and Public Health, Via San Sisto 22/E, 67100 L'Aquila, Italy.
[Ginaldi, Lia] University of L'Aquila, Department of Internal Medicine and Public Health, Via San Sisto 22/E, 67100 L'Aquila, Italy.
RP De Martinis, M (reprint author), University of L'Aquila, Department of Internal Medicine and Public Health, 67100 L'Aquila, Italy.
EM demartinis@sscaq1.cc.univaq.it
CR Adany R: Intracellular factor XIII: cellular distribution of factor XIII subunit A in humans. Semin Thromb Hemost 22:399- 408, 1996.
Bardos H, Juhansz A, Repassy G, et al: Fibrin deposition in squamous cell carcinomas of the larynx and hypopharynx. Thromb Haemost 80:767-772, 1998.
Baron JA, Gridley G, Weiderpas E, et al: Venous thromboembolism and cancer. Lancet 351:1077-1080, 1998.
Bastida E, Ordinas A, Jamieson GA: Differing platelets aggregating effects by two tumor cells lines: absence of a role for platelet-derived ADP. Am J Hematol 11:367-378, 1981.
Bergqvist D, Burmark US: Low-molecular-weight heparin started before surgery as prophylaxis against deep-vein thrombosis: 2500 versus 5000 anti-Xa units in 2070 patients. Br J Surg 82:496-501, 1995.
Bertomeu MC, Gallo S, Lauri D Levine MN, et al: Chemotherapy enhances endothelial reactivity to platelets. Clin Expl Metastasis 8:511-518, 1990.
Bick RL. Alterations of hemostasis associated with malignancy: etiology, pathophysiology, diagnosis and management. Semin Thromb Hemost 5:1-26, 1978.
Bottasso B, Mari D, Coppola R, et al: Hypercoagulability and hyperfibrinolysis in patients with melanoma. Thromb Res 81:345-352, 1996.
Brown LF, Detmar M, Claffey KP: Vascular permeability factor/ vascular endothelial growht factor: a multifunctional angiogenesis factor. In: Goldberg ID, Rosen EM, eds. Regulation of Angiogenesis. Basel Birgkhauser Verlag, 233-269;
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Calvo FA, Hidalgo OF, Gonzales F, et al: Urokinase combination chemotherapy in small cell lung cancer. A phase II study. Cancer 70:2624-2630, 1992.
Carey MG, Rodgers GM: Disseminated intravascular coagulation: clinical and laboratory aspects. Am J Hematol 59:65-73, 1998.
Chahinian AP, Propert KJ, Ware JH, et al: A randomized trial of anticoagulation with warfarin and alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol 7:993-1002, 1989.
Chan A, Woodruff RK: Complication and failure of anticoagulation therapy in the treatment of venous thromboembolism in patients with disseminated malignancy. Aust NZ J Med 22:119-122, 1992.
Chen YQ, Trikha M, Gao X, et al: Ectopic expression of platelet integrin alphaIIb beta3 in tumor cells from various species and histological origin. Int J Cancer 72:642-648, 1997
Clauss M, Gerlach M, Geralach H, et al:Vascular permeabiliy factor: a tumor-derived polypeptide that induce endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172:1535-1545, 1990.
Colman RW, Rubin RN: Disseminated intravascular coagulation due to malignancy. Semin Oncol 17:140-146, 1990.
Cornuz J, Pearson SD, Creager MA, et al: Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med 60:257-277, 1996.
Cybulsky MI, Chan MKW, Movat HZ. Acute inflammation and microthrombosis induced by endotoxin, interleukin-1 and tumor necrosis factor and their implication in gram negative infection. Lab Invest 58:365-368, 1988.
DeLisser HM, Christofidou-Solomidou M, Strieter RM, et al: Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 151:671-677, 1997
Dittman WA, Majerus PW: Structure and function of thrombomodulin: a natural anticoagulant. Blood 75:329-336, 1990.
Dolovich L, Ginsberg JS: Low-molecular weight heparins in the treatment of venous thromboembolism. Vessels 3:4-11, 1997.
Donati MB, Gambacorti-Passerinin C, et al: Cancer procoagulant in human tumor cells: Evidence from melanoma patients. Cancer Res 46: 6471-6474, 1986.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2000
VL 6
IS 4
BP 301
EP 312
PG 12
ER
PT J
AU Forgacs, E
Zochbauer-Muller, S
Olah, E
Minna, DJ
AF Forgacs, Eva
Zochbauer-Muller, Sabine
Olah, Edit
Minna, D John
TI Molecular Genetic Abnormalities in the Pathogenesis of Human Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE oncogene; tumor suppressor gene; autocrine; signal transduction; cell cycle; mutation; methylation; telomerase; angiogenesis; preneoplasia
ID oncogene; tumor suppressor gene; autocrine; signal transduction; cell cycle; mutation; methylation; telomerase; angiogenesis; preneoplasia
AB In the past few years our knowledge of the molecular pathogenesis of lung cancer has significantly increased. There are several molecular mechanisms involved in the multistage carcinogenesis through which respiratory epithelial cells become preneoplastic and then invasive cancer. In this review we summarize some of these changes including, genomic alterations such as loss of heterozygosity and microsatellite alterations, autocrine-paracrine loops, alterations in oncogenes and tumor suppressor genes, tumor angiogenesis, aberrant promoter methylation and inherited predisposition to lung cancer. Translation of these findings to the clinic is also discussed.
C1 [Forgacs, Eva] University of Texas Southwestern Medical Center at Dallas, Hamon Center for Therapeutic Oncology Research, 6000 Harry Hines Blvd, 75390-8593 Dallas, TX, USA.
[Zochbauer-Muller, Sabine] University of Texas Southwestern Medical Center at Dallas, Hamon Center for Therapeutic Oncology Research, 6000 Harry Hines Blvd, 75390-8593 Dallas, TX, USA.
[Olah, Edit] National Institute of Oncology, Department of Biochemistry, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Minna, D John] University of Texas Southwestern Medical Center at Dallas, Hamon Center for Therapeutic Oncology Research, 6000 Harry Hines Blvd, 75390-8593 Dallas, TX, USA.
RP Minna, DJ (reprint author), University of Texas Southwestern Medical Center at Dallas, Hamon Center for Therapeutic Oncology Research, 75390-8593 Dallas, USA.
EM John.Minna@UTSouthwestern.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 6
EP 13
PG 8
ER
PT J
AU John, A
Tuszynski, G
AF John, Anitha
Tuszynski, George
TI The Role of Matrix Metalloproteinases in Tumor Angiogenesis and Tumor Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE matrix metalloproteinases; metalloproteinase inhibitors; gelatinases; tumor angiogenesis; metastasis
ID matrix metalloproteinases; metalloproteinase inhibitors; gelatinases; tumor angiogenesis; metastasis
AB Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.
C1 [John, Anitha] MCP Hahnemann University, Department of PathologyPhiladelphia, USA.
[Tuszynski, George] MCP Hahnemann University, Department of PathologyPhiladelphia, USA.
RP Tuszynski, G (reprint author), MCP Hahnemann University, Department of Pathology, Philadelphia, USA.
EM george.tuszynski@drexel.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 14
EP 23
PG 10
ER
PT J
AU Dursun, A
Poyraz, A
Suer,
Sezer, C
Akyol, G
AF Dursun, Ayse
Poyraz, Aylar
Suer, Ozlem
Sezer, Cem
Akyol, Gulen
TI Expression of Bcl-2 and c-ErbB-2 in Colorectal Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bcl-2; c-ErbB-2; colorectal neoplasia
ID Bcl-2; c-ErbB-2; colorectal neoplasia
AB Several studies have been demonstrated the value of c-ErbB-2 and Bcl-2 in predicting the biological behaviour of tumors. The aim of this study was to investigate Bcl-2 and c-ErbB-2 expression in colorectal carcinomas and the correlation between their presence and other clinicopathologic parameters. Eighty-six colorectal carcinomas and 17 adenomas were stained with Bcl-2 and c-ErbB-2 immunohistochemically. Staining patterns were assessed semi-quantitatively and correlated with tumor size, Duke’s classification, tumor differentiation, mucinous characteristic and anatomic locations. We detected Bcl-2 expression in 10 of 17 adenomas (58.8 %) and 31 of 86 carcinomas (36.04 %). Positive staining in normal mucosa was observed only in the compartment of cryptic cells. However neither the difference in the rates of Bcl-2 positivity in adenoma and carcinoma groups, nor the correlation with other mentioned clinicopathological parameters, were found statistically significant. Bcl-2 expression was found to be significantly high in mucinous carcinomas. Expression of c-ErbB-2 was observed in 12 of 86 (13.95 %) carcinomas. It was not detected in adenomas and normal mucosa. Although the incidence of c-ErbB-2 in nonmucinous carcinoma was higher than that of mucinous carcinoma, this was not significant. In addition we were unable to show any significant relation between c-ErbB-2 expression and other clinicopathologic features. Our result suggest that c-ErbB-2 protein expression in colorectal carcinomas, is not very frequent event. There is no correlation between c-ErbB-2 expression and malignant potential of colorectal carcinomas. Higher expressions of Bcl-2 in adenomas than carcinomas suggest us a possible role of Bcl-2 in early carcinogenesis of colon. However since we were unable to find any significant correlation between Bcl-2 expression and other parameters the impact of this gene on biological behavior is still unclear for us.
C1 [Dursun, Ayse] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8 Mebu-sevleri-Tandosan, 06580 Ankara, Turkey.
[Poyraz, Aylar] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8 Mebu-sevleri-Tandosan, 06580 Ankara, Turkey.
[Suer, Ozlem] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8 Mebu-sevleri-Tandosan, 06580 Ankara, Turkey.
[Sezer, Cem] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8 Mebu-sevleri-Tandosan, 06580 Ankara, Turkey.
[Akyol, Gulen] Gazi University Faculty of Medicine, Department of Pathology, Turgut Reis Caddesi 16/8 Mebu-sevleri-Tandosan, 06580 Ankara, Turkey.
RP Dursun, A (reprint author), Gazi University Faculty of Medicine, Department of Pathology, 06580 Ankara, Turkey.
EM aylarpoyraz@superonline.com
CR Baretton GB, Diebold J, Christoforis, et al: Apoptosis and immunohistochemical Bcl-2 expression in colorectal adenomas and carcinomas. Cancer 77:255-264, 1996.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 24
EP 27
PG 4
ER
PT J
AU Kleist, B
Bankau, A
Lorenz, G
Poetsch, M
AF Kleist, Britta
Bankau, Alexander
Lorenz, Gerd
Poetsch, Micaela
TI Multiple Chromosomal Underrepresentations Detected by Interphase Cytogenetics - Possible Prognostic Markers in Head and Neck Tumors?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck carcinoma; FISH; numerical chromosomal aberrations; TNM status; grading
ID head and neck carcinoma; FISH; numerical chromosomal aberrations; TNM status; grading
AB Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.
C1 [Kleist, Britta] University of Greifswald, Institute of Pathology, F.-Loeffler-Strasse 23e, D-17489 Greifswald, Germany.
[Bankau, Alexander] University of Greifswald, Department of OtorhinolaryngologyGreifswald, Germany.
[Lorenz, Gerd] University of Greifswald, Institute of Pathology, F.-Loeffler-Strasse 23e, D-17489 Greifswald, Germany.
[Poetsch, Micaela] University of Greifswald, Institute of Forensic MedicineGreifswald, Germany.
RP Kleist, B (reprint author), University of Greifswald, Institute of Pathology, D-17489 Greifswald, Germany.
CR Ambrosch P, Kron M, Fischer G, et al: Micrometastasis in carcinoma of the upper aerodigestive tract: detection, risk of metastasizing, and prognostic value of depth of invasion. Head Neck 17:473-479, 1995.
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Bailey BJ: Beyond the “new“ TNM classification. Arch Otolaryngol Head Neck Surg 117:369-370, 1991.
Berenson JR, Yang J, Mickel RA: Frequent amplification of the bcl-1 locus in head and neck squamous cell carcinomas. Oncogene 4:1111-1116, 1989.
Cowan JM, Beckett MA, Ahmed-Swan S, et al: Cytogenetic evidence of the multistep origin of head and neck squamous cell carcinomas. J Natl Cancer Inst 84:793-797, 1992.
Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61:759-767, 1990.
Greenman J, Homer JJ, Stafford ND: Markers in cancer of the larynx and pharynx. Clin Otolaryngol 25:9-18, 2000.
Harada Y, Toyomasa K, Ito I, et al:Genetic studies of 457 breast cancers. Clinicopathologic parameters compared with genetic alterations. Cancer 74:2281-2286, 1994.
Hunter T: Cooperation between oncogenes. Cell 64:249-270, 1991.
Jakobson J, Hansen O, Jorgensen KE, et al: Lymph node metastasis from laryngeal and pharyngeal carcinomas-calculation of burden of metastasis and its impact on prognosis. Acta Oncol 37:489-493, 1998.
Jin Y, Mertens F, Mandahl N, et al: Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas: influence of culture conditions on karyotypic pattern. Cancer Res 53:2140-2146, 1993.
Li X, Lee NK, Ye Y-W, et al: Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor prognosis in head and neck cancer. J Natl Cancer Inst 86:1524-1529, 1994.
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Matthias C, Jahnke V, Hand P, et al: Immunhistologic and molecular genetic studies of the effect of glutathione-S-transferases on the development of squamous epithelial carcinomas in the area of the head and neck. Laryngorhinootologie 78:182-188, 1999.
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Poetsch M, Woenckhaus C, Dittberner T, et al: Increased frequency of numerical chromosomal abnormalities and 1p36 deletions in isolated cells of paraffin sections of malignant melanoma detected by interphase cytogenetics. Cancer Genet Cytogenet 104:146-52, 1998.
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Raitiola H, Pukander J, Laippala P: Glottic and supraglottic laryngeal carcinoma: differences in epidemiology, clinical characteristics and prognosis. Acta Otolaryngol 119:847-851, 1999.
Richter J, Wagner U, Schrami P, et al: Chromosomal imbalances are associated with a high risk of progression in early invasive, pT1, urinary bladder cancer. Cancer Res 59:5687- 5691, 1999.
Saretzki G, Hoffmann U, Rohlke P, et al: Identification of allelic loses in benign, borderline, and invasive epithelial ovarian tumors and correlation with clinical outcome. Cancer 80:1241- 1248, 1997.
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Wiernik G, Millard PR, Haybittle JL: The predictive value of histological classification into degrees of differentiation of squamous cell carcinoma of the larynx and hypopharynx compared with the survival of patients. Histopathology 19:411-417, 1991.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 28
EP 32
PG 5
ER
PT J
AU Bayramoglu, H
Duzcan, E
AF Bayramoglu, Hatice
Duzcan, Ender
TI Atypical Epithelial Changes and Mutant p53 Gene Expression in Ovarian Endometriosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ovarian endometriosis; atypia; p53
ID ovarian endometriosis; atypia; p53
AB It has been reported that cases of ovarian endometriosis those with epithelial cytological atypia have potential for malignant transformation. This study was planned to determine the incidence of atypical endometriosis and its cytological criteria, to evaluate the malignant potential of atypical endometriosis via immunohistochemical methods (p53). In this study we evaluated 140 samples obtained from 120 cases of ovarian endometriosis and 10 ovarian endometrioid carcinomas that have been previously diagnosed histopathologically. We re-evaluated endometriosis cases with respect to their epithelial and stromal features, existence of acute or chronic inflammatory cells in endometriotic epithelium or stroma and other accompanying histological findings. We observed atypia in 7 (5.8%) cases; reactive atypia in 37 (30.8%) cases, no atypia in 76 (63.4%) cases. We evaluated immunohistochemical p53 expression in 7 atypical cases, 37 reactive atypical cases, and in 10 of those without atypia and in 10 endometrioid carcinoma cases. We noted no staining in cases with atypia, reactive atypia and without atypia while 3 cases of endometrioid carcinoma had positive staining for p53. We concluded that prominent nucleolus and angulation of nuclear contour could be added to criteria of atypia that were mentioned before in the literature. In our study, even though p53 expression could not be shown with immunohistochemical methods in atypical endometriotic cases; it can not be determined that atypical endometriosis lesions are not premalignant. Still, endometriosis cases should be evaluated carefully by the pathologist for foci of cytological atypia and it should be kept in mind that malignant transformation might occur in these atypical endometriosis cases.
C1 [Bayramoglu, Hatice] Pamukkale University, Faculty of Medicine, Department of Pathology, Atakent Mh. Esnaf Sitesi, Sardunya Sk. No:17Denizli, Turkey.
[Duzcan, Ender] Pamukkale University, Faculty of Medicine, Department of Pathology, Atakent Mh. Esnaf Sitesi, Sardunya Sk. No:17Denizli, Turkey.
RP Bayramoglu, H (reprint author), Pamukkale University, Faculty of Medicine, Department of Pathology, Denizli, Turkey.
EM hbayramoglu@hotmail.com
CR Clement PB: Diseases of the Peritoneum, In Kurman RJ ed. Blaustein’s Pathology of the Female Genital Tract. New York: Springer-Verlag, 1994, pp660-680.
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Clement PB, Young RH, Scully RE: Peritoneum. In Sternberg SS ed. Diagnostic Surgical Pathology. New York, Raven Press Ltd., 1994, pp 2311-2315.
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LaGrenade A, Silverberg SG: Ovarian tumors associated with atypical endometriosis. Human Pathol 19:1080-1084, 1988.
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De La Cuesta RS, Eichhorn JH, Rice LW, et al: Histologic transformation of benign endometriosis to early epithelial ovarian cancer. Gynecol Oncol 60:238-244, 1996.
Granai CO, Walters MD, Safai H, et al: M: Malignant transformation of vaginai endometriosis. Obstet Gynecol 64:592-595, 1984.
Brooks JJ, Wheeler JE: Malignancy arising in extragonadal endometriosis. Cancer 10:3065-3073, 1977.
Horiuch A, Osada R, Nakayama K, et al: Ovarian yolk sac tumor with endometrioid carcinoma arising from endometriosis in a postmenopausal woman, with special reference to expression of alpha-fetoprotein, sex steroid receptora, and p53. Gynecol Oncol 70:295-299, 1998.
Han AC, Hovenden S, Rosenblum NG, Salazar H: Adenocarcinoma arising in extragonadal endometriosis: an immunohistochemical study. Cancer 83:1163-1169, 1998.
Czernobilsky B, Morns WJ: A histologic study of ovarian endometriosis with emphasis on hyperplastic and atypical changes. Obstet Gynecol 53:318-323, 1979.
Chalas E, Chumas J, Barbien R, Mann WJ: Nucleolar organizer regions in endometriosis, atypical endometriosis, and clear cell and endometrioid carcinoma. Gynecol Onco140:260-263, 1991.
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Kawai A, Noguchi M, Beppu Y, et al: Nuclear immunoreaction of p53 protein in soft tissue sarcomas. Cancer 73:2499-2505, 1994.
Deb S, Jackson CT, Subler MA, Martin DW: Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cella. J Virol 66:6164-6170, 1992.
Harris AL: p53 expression in human breast cancer. Advances Cancer Res 59:69-88, 1992.
Rotter V, Prokocimer M: p53 and human malignancies. Advances Cancer Res 57: 257-272, 1991.
Walker C, Robertson LJ, Myskow MW, et al: p53 expression in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer 70:297-303, 1994.
Fontanini G, Vignati S, Bigini D, et al: Human non- small cell lung cancer: p53 protein accumulation is an early event and parsists durrog metastatic progression. J Pathol 174:23-31, 1994.
Bennett Wp, Hollstein MC, Metcalf RA, et al: p53 mutation and protein accumulation durrog multistage human esophageal carcinogenesis. Cancer Res 52:6092-6097, 1992.
Fukunaga M, Nomura K, Ishikawa E, et al: Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology 30:249-255, 1997.
Seidmann JD: Prognostic importence of hyperplasia and atypia in endometriosis. Int J Gynecol Pathol 15:1-9, 1996.
Erhan Y, Postaci H: Over endometriozlarmda histolojik ozellikler, Ízmir Devlet Hastanesi Mecmuasi. 21:254-261, 1983.
Karseladze AI: Ovarian endometriosis. Arch Pathol 52:24-29, 1990.
Marks JR, Davidoff AM, Kerns BJ, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51:2979-2984, 1991.
Harlozinska A, Bar JK, Sedlaczek P, Gerber J: Expression of p53 protein and Ki-67 reactivity in ovarian neoplasms. Am J Clin Pathol 105:3340-3345, 1996.
Koshiyama M, Konishi I, Mandai M, et al: Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein, HSP72, expression in ovarian carcinomas. Correlation with clinicopathology and sex steroid receptor status. Virchows Arch 425:603-609, 1995.
Niwa K, Itoh M, Murase T, et al: Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance. Br J Cancer 70:1191-7, 1994.
Kappes S, Milde-Langosch K, Kressin P, et al: p53 mutations in ovarian tumors, detected by temperatere-gradient gel electrophoresis, direct sequencing and immunohistochemistry. Int J Cancer 64:52-59, 1995.
Kargi HA, Sagol O, Ozuysal S: The immunohistochemical expression of proliferating cell nuclear antige c-erbB2 and p53 in benign, borderline and malignant epithelial ovarian neoplasms. Turkish J Cancer 27:13-18, 1997.
Eccles DM, Brett L, Lessek A, et al: Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. Br J Cancer 65:40-44, 1992.
Schneider J, Jimenez E, Rodriguez F, et al: C-myc, c-erb-B2, nm23 and p53 expression in human endometriosis. Oncol Rep 5:49-52, 1998.
Kupryjanczyk J, Bell DA, Yandell DW, et al: p53 expression in ovarian borderline tumor and stage I carcinomas. Am J Clin Pathol 102:671-676, 1994.
Cattoretti G, Rilke F, Andreola S, et al: p53 expression in breast cancer. Int J Cancer 41:178-183, 1988.
Haerslev T, Jacobsen GK: An immunohistochemical study of p53 with correlations to histopathological parameters, c-erb-2, proliferating cell nuclear antigen, and prognosis. Hum Pathol 26:295-301, 1995.
Akasofu M, Oda Y: Immunohistochemical detection of in cervical epithelial lesions with or without infection of human papillomavirus types 16-18. Virchows-Arch 425:593-602, 1995.
Martmez J, Georgoff I, Martmez J, et al: Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Development 5:151-159, 1991.
Iggo R, Gatter K, Bartek J, et al: Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335;675-679, 1990.
Wynford-Thomas D: p53 in tumour pathology: Can we trust immunocytochemistry? J Pathol 166:329-330, 1992.
Zhao M, Zhang NX, Laissue SA, Zimmermann A: Immunohistochemical analysis of p53 protein over expression in liver cell dysplasia and in hepatocellular carcinoma. Virchows Archiu 424:613-621, 1994.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 33
EP 38
PG 6
ER
PT J
AU Ghaderi, AA
Talei, AAR
Gharesi-Fard, B
Farjadian, HF
Amirzargar, AA
Vasei, M
AF Ghaderi, Ali Abbas
Talei, Abd-Al-Rasoul
Gharesi-Fard, Behronz
Farjadian, H F
Amirzargar, Ali-Akbar
Vasei, Mohammad
TI HLA-DRB 1 Alleles and the Susceptibility of Iranian Patients with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; HLA-DRB1; PCR-SSP
ID breast cancer; HLA-DRB1; PCR-SSP
AB Breast cancer is considered a major malignancy among women worldwide. The contribution of genetic elements to the onset of familial breast cancer has already been established. The current study investigate the alfele frequency of HLA-DRB 1 in 36 primary operable female breast cancer patients from southern Iran by polymerase chain reaction using sequence specific primers (PCR-SSP). Results were compared with those of 36 female control subjects. Statistical analysis was performed and P values were determined for each character. Our results indicated that the frequency of HLA-DRB 1*12 allele is significantly higher in the patient group (p<0.03) compared to the control group. In addition, HLA-DRB1*11 appeared to be as the most frequent allele in the control group (29.2%) and had approximately the same distribution among the patient group (22.5%).
C1 [Ghaderi, Ali Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Talei, Abd-Al-Rasoul] Medical School, Shiraz University of Medical Sciences, Department of SurgeryShiraz, Iran.
[Gharesi-Fard, Behronz] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Farjadian, H F] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Amirzargar, Ali-Akbar] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Vasei, Mohammad] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
RP Ghaderi, AA (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM immunol@sums.ac.ir
CR Garfinkel L, Catherine C, Boring MPH, et al: An overview of breast cancer incidence and mortality. Cancer 74:222-227, 1994.
Szabo CI, King MC: Population genetics of BRCA1 and BRCA2. Am J Hum Genet 60:1013-1020, 1997.
Miki Y, Swense J, Shatuck-Eidens D, et al: A strong candidate for the breast and ovarian cancer susceptibility. Science 266:66-71, 1994.
Reiter DJ, Brocker EB, Ferrone S: Expression and susceptibility of modulation by interferones of HLA-class I and II antigens on melanoma cells. Immunohistochemical analysis and clinical relevance. J Immunogenetics 13:229-234, 1986.
Glew SS, Duggan-Keen M, Cabrera T, et al: HLA-class II antigen expression in human papilomavirus-associated cervical cancer. Cancer Res 52:4009-4016, 1992.
Paterson AC, Sciot R, Kew MC, et al: HLA expression in human hepatocellular carcinoma. Br J Cancer 57:369-373, 1988.
van den Ingh HF, Ruiter DJ, Griffioen G, et al: HLA antigens in colorectal tumours-low expression of HLA class I antigens in mucinous colorectal carcinomas. Br J Cancer 55:125-130, 1987.
Tokumoto H: Analysis of HLA-DRB1-related alleles in Japanese patients with lung cancer-relationship to genetic susceptib~ lity and resistance to lung cancer. J Cancer Res Clin Oncol 124:511-516, 1988.
Graham DE:The isolation of high molecular weight DNA from whole organisms or large tissue masses. Anal Biochem 85:609- 613, 1978.
Miller SA, Dykes DD, Polesky IF: A simple sahing out procedure for extracting DNA from human nucleated cells. Nucl Acid Res 16:1215, 1988.
Olerup O, Zetterquist H: HLA-DR typing by PCR amplification with PCR-SSP in two hours. Tissue Antigens 39:225-235, 1992.
Casoli C, Zanelli P, Adorni A, et al: Serological and molecular study on the HLA phenotype of female breast cancer patients. Europ J Cancer 30A:1207-1208, 1994.
Pardon DM, Topalian SL: The role of CD4+ T cells responses in antitumor immunity. Curr Opin Immunol 10:588-589, 1998.
Armstrong TD, Klements VK, Ostrand-Rosenberg S:MHC class II-transfected tumor cells directly present antigen to tumor specific CD4+ T lymphocytes. J Immunol 160:660-666, 1998.
Armstrong TD, Klements VK, Ostrand-Rosenberg S: ClassIItransformed tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigen in vivo. J Immunother 21:218-224, 1998.
Feinmesser M, Sulkes A, Morgenstern S, et al: HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities. J Clin Pathol 53:286-291, 2000.
Dadmarz R, Sgagias MK, Rosenberg SA, et al: CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in an MHC-class-II restricted fashion. Cancer Immunol Immunother 40:1-9, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 39
EP 41
PG 3
ER
PT J
AU Magyarlaki, T
Buzogany, I
Nagy, J
AF Magyarlaki, Tamas
Buzogany, Istvan
Nagy, Judit
TI Specific von Hippel-Lindau Protein Expression of Clear Cell Renal Cell Carcinoma with ''Immunogenic” Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE clear cell renal cell carcinoma; von Hippel-Lindau protein; tumor infiltrating lymphocytes; immune complexes
ID clear cell renal cell carcinoma; von Hippel-Lindau protein; tumor infiltrating lymphocytes; immune complexes
AB Human clear cell renal cell carcinoma (CCRCC) is characterized by specific von Hippel-Lindau (VHL) gene alterations and ''immunogenic” features. In the present study, the immunohistochemical expression of the von Hippel-Lindau gene protein (pVHL) was compared with the presence of major histocompatibility complex (MHC I-II), tumor infiltrating lymphocytes (TIL) and tumoral immune complexes (TIC) in CCRCC. Native tumor tissues of 132 RCC patients (95 with the common clear cell subtype), diagnosed according to the Heidelberg classification, were obtained for immunohistochemistry. Tumor stainings with pVHL, MHC I-II and tumor infiltrating lymphocytes (T and B lymphocytes, monocytes) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (IgG, IgA, IgM and C1q, C3 complement proteins) were visualized by fluorescent polyclonal antibodies. Immune stainings were semiquantitatively evaluated. Specificity and sensitivity of these markers in relation to the common histological subtype of RCC (CCRCC) were calculated. CCRCC was characterized by specific pVHL expression. At the same time, CCRCC was associated with constitutional MHC I-II expression and highly specific degree of TIL and TIC. It is concluded that specific pVHL expression of CCRCC is frequently associated with ''immunogenic” features. Immunohistochemical analysis aims the initial tumor staging of RCC patients to achieve better patient selection for immunotherapy. However, the association of pVHL expression with the ''immunogenic” CCRCC is statistically relevant, the mechanism and its clinical relevance in immunotherapy still remains to be tested.
C1 [Magyarlaki, Tamas] University of Pecs, Institute of Biochemistry and Medical Chemistry, Ifjusag utja 13, 7624 Pecs, Hungary.
[Buzogany, Istvan] University of Pecs, Department of UrologyPecs, Hungary.
[Nagy, Judit] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
RP Magyarlaki, T (reprint author), University of Pecs, Institute of Biochemistry and Medical Chemistry, 7624 Pecs, Hungary.
EM mlaki@clinics.pote.hu
CR Belldegrun A, Tao CL, Kaboo R, et al: Natural immune reactivity- associated therapeutic response in patients with metastatic renal cell carcinoma receiving tumor-infiltrating lymphocytes and interleukin-2-based therapy. J Immunother Emphasis Tumor Immunol 19:149-161, 1996.
van Bezooijen RL, Goey H, Stoter G, et al: Prognostic markers for survival in patients with metastatic renal cell carcinoma treated with interleukin-2. Cancer Immunol Immunother 43:293-298, 1996.
Brauch H, Weirich G, Brieger J, et al: VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Cancer Res 60:1942-1948, 2000.
Buszello H, Ackermann R:Immunohistochemical studies on the expression of HLA Class I antigen in renal cell carcinoma: comparison of primary and metastatic tumor tissue. Eur Urol 25:158-163, 1994.
Corless CL, Kibel AS, Iliopoulos O, et al: Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum Pathol 28:459-463, 1996.
Van den Hove LE, van Gool S.W, van Poppel H, et al: Identification of an enriched CD4+ CD8alpha++ CD8beta+ T-cell subset among tumor-infiltrating lymphocytes in human renal cell carcinoma. Int J Cancer 71:178-182, 1997.
Van den Hove LE, van Gool SW, van Poppel H, et al: Phenotype, cytokine production and cytolytic capacity of fresh, uncultured, tumor-infiltrating T lymphocytes in human renal cell carcinoma. Clin Exp Immunol 109:501-509, 1997.
Jantzer P, Schendel DJ: Human renal cell carcinoma antigenspecific CTLs: antigen-driven selection and long-term persistence in vivo. Cancer Res 58:3078-3086, 1998.
Kawata N, Akimoto Y, Hirano, et al: Immunological effect of recombinant interferon-gamma on tumor infiltrating lymphocytes of renal cell carcinoma – relationshship with clinical stage, Japanese). Hinyokika-Kiyo 42:1-4, 1996.
Kovacs Gy, Akhtar M, Beckwith BJ, et al: The Heidelberg classification of renal cell tumors. J Pathol 183:131-133, 1997.
Kowalczyk D, Skorupski W, Kwias Z, et al: Flow cytometric analysis of tumor-infiltrating lymphocytes in patients with renal cell carcinoma. Br J Urol 80:543-547, 1997.
Licht MR, Novick AC, Tubbs RR, et al: Renal oncocytoma: clinical and biological correlates. J Urol 150:1380-1383, 1993.
Magyarlaki T, Mosolits S, Baranyay F, et al: Immunohistochemistry of complement responses on human renal cell carcinoma biopsies. Tumori 82:473-480, 1996.
Magyarlaki T, Kiss B, Buzogany I, et al: Renal cell carcinoma and paraneoplastic IgA nephropathy. Nephron 82:127-130, 1999.
Toliou T, Stravoravdi P, Polyzonis M, et al: Natural killer cell activation after interferon administration in patients with metastatic renal cell carcinoma: an ultrastructural and immunohistochemical study. Eur Urol 29:252-256, 1996.
Vogelzang NJ, Stadler WM: Kidney cancer. Lancet 352:1691- 1696, 1998.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 42
EP 45
PG 4
ER
PT J
AU Gupta, N
Sarkar, Ch
Singh, R
Karak, KA
AF Gupta, Nimisha
Sarkar, Chitra
Singh, Rajvir
Karak, Kumar Asis
TI Evaluation of Diagnostic Efficiency of Computerized Image Analysis Based Quantitative Nuclear Parameters in Papillary and Follicular Thyroid Tumors Using Paraffin-Embedded Tissue Sections
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE thyroid tumor; image analysis; quantitative nuclear morphometry; papillary carcinoma; follicular neoplasm
ID thyroid tumor; image analysis; quantitative nuclear morphometry; papillary carcinoma; follicular neoplasm
AB Computerized image analysis (IA) system has emerged in recent years as a very powerful tool for objective and reproducible quantification of histological features. It has shown considerable potential for diagnostic application in diverse histological situations. The objectives of the present study were to evaluate the discriminatory diagnostic efficiency of computerized image analysis based quantitative subvisual nuclear parameters in papillary and follicular neoplasms of thyroid. A total of 60 cases were studied. Forty-four cases belonged to training set and 16 cases belonged to a test set. A minimum of 100 nuclei was analyzed in each case using uniform 5 m mm thick hematoxylin stained sections. The IA workstation comprised of an Olympus microscope, a 10 bit digital video camera, an image grabber card and a pentium 120 MHz computer. Optimas 5.2 software was utilized for data collection on 8 morphometric and 8 densitometric parameters. Multivariate stepwise discriminant statistical analysis of data was done with the help of BMDP statistical software release 7.0. Results from a training set revealed correct classification rates of 98.0%, 84.5% and 61.2% for the histological groups of hyperplastic papillae versus papillae of papillary carcinoma (group I), follicular variant of papillary carcinoma versus the broad category of follicular neoplasms consisting of both follicular adenoma and follicular carcinoma (group II) and follicular adenoma versus follicular carcinoma (group III), respectively. Results of test set revealed correct classification rates of 100%, 80% and 50% for groups I, II and III respectively. It was concluded that computerized nuclear IA parameters have potential usefulness for discriminating benign versus malignant papillary lesions of thyroid, follicular variant of papillary carcinoma versus follicular adenoma and/or follicular carcinoma but are of no value in discriminating between follicular adenoma and follicular carcinoma.
C1 [Gupta, Nimisha] All India Institute of Medical Sciences, Department of Pathology and Biostatistics, 110029 New Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology and Biostatistics, 110029 New Delhi, India.
[Singh, Rajvir] All India Institute of Medical Sciences, Department of Pathology and Biostatistics, 110029 New Delhi, India.
[Karak, Kumar Asis] All India Institute of Medical Sciences, Department of Pathology and Biostatistics, 110029 New Delhi, India.
RP Karak, KA (reprint author), All India Institute of Medical Sciences, Department of Pathology and Biostatistics, 110029 New Delhi, India.
EM akkarak@hotmail.com
CR Ain KB: Papillary thyroid carcinoma. Etiology, assessment and therapy. Endocrinol Metab Clin North Amer 24:711-760, 1995.
Artacho-Perula E, Roldan-Villalobos R, Blanco-Garcia F, et al: Objective differential classification of thyroid lesions by nuclear quantitative assessment. Histol. Hisopathol 12:425- 431, 1997.
Auer G, Askensten U, Ahrens O: Cytophometry. Hum Pathol 20:518-527, 1989.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 46
EP 55
PG 10
ER
PT J
AU Kravchick, S
Gal, R
Cytron, Sh
Peled, R
Weissman, Y
Mukamel, E
Koren, R
AF Kravchick, Sergey
Gal, Rivka
Cytron, Shmuel
Peled, Ronit
Weissman, Yona
Mukamel, Eliahu
Koren, Rumelia
TI Increased Incidence of Diabetes Mellitus in the Patients with Transitional Cell Carcinoma of Urinary Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urinary bladder; transitional cell carcinoma; diabetes mellitus
ID Urinary bladder; transitional cell carcinoma; diabetes mellitus
AB The progression of bladder cancer to invasive disease is highly dependent on its ability to penetrate basement membrane of urothelium. Studies on diabetic nephropathy have shown a reduction in pro-teoglycan content of the glomerular basement membrane. Based on the well-known fact that proteoglycans are one of the main components of basement membrane and extracellular matrix we assessed the relationship between diabetes mellitus, bladder cancer incidence and its behavior. These studies include 252 patients with microscopically confirmed transitional cell carcinoma of bladder, and 549 patients with other urological disorders who served as controls. The prevalence of diabetes mellitus in each group was assessed. The group of patients suffering from transitional cell carcinoma was divided according to etiological risk factors such as cigarette smoking, diabetes and patients that were non-smokers and did not suffer from diabetes mellitus. We assessed the features of bladder cancer behavior in each group. Logistic regression model estimation for statistical analysis was used, with transitional cell carcinoma as a dependent binary variable and age, sexes smoking and diabetes as independent variables. Statistical significance was considered at two levels: p £ £0.001 and p £ £0.05. Odds ratio (OR) adjusted to age, sex, cigarette smoking, diabetes mellitus and 95% Confidence Interval (CI) were calculated for TCC. In the TCC group 22.2% of the patients suffered from diabetes mellitus. In the control group 10.38% suffered from diabetes mellitus. Logistic regression analysis, OR and 95% CI showed a statistically significant relationship between diabetes and TCC. These data are comparable only with smoking (OR – 2.3; 95% CI – 1.6 – 3.5 and OR– 1.58; 95% CI – 1.08 – 2.4 correspondingly). Based on these data we suggest that diabetes mellitus may be considered an etiological risk factor for bladder cancer development.
C1 [Kravchick, Sergey] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Gal, Rivka] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Cytron, Shmuel] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Peled, Ronit] Barzilay Medical Center, Epidemiology UnitAshkelon, Israel.
[Weissman, Yona] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Mukamel, Eliahu] Hasharon Hospital, Department of UrologyPetach Tikvah, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
RP Gal, R (reprint author), A, Rabin Medical Center (Golda Campus), Department of Pathology, Petach Tikvah, Israel.
EM rumelia@isdn.mail.co.il
CR Cotran RS, Kumar V, Robbins SL, et al: Pathologic basis of disease, 5th ed, WB Saunders Co, Philadelphia, Pennsylvania, 1994.
Hayes RB, Friedell GH, Zahm SH, et al: Are the known bladder cancer risk factors associated with more advanced bladder cancer? Cancer Causes Control 4:157-162, 1993.
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Silverman DT, Hartge P, Morrison AS, et al: Epidemiology of bladder cancer. Hematol Oncol Clin North Am 6:1-30, 1992.
Wilkens LR, Kadir MM, Kolonel LN, et al: Risk factors for lower urinary tract cancer: the role of total fluid consumption, nitrites and nitrosamines, and selected foods. Cancer Epidemiol Biomarkers Prev 5:161-166, 1996.
Asten P, Barrett J, Symmons D: Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases. J Rheumatol 26:1705-1714, 1999.
Liu BC, Liotta LA:Biochemistry of bladder cancer invasion and metastasis. Urol Clin North Am 19:621-627, 1992.
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Sinclair AJ: Diabetes in the elderly: A perspective from the United Kingdom. Clin Geriatr Med 15:225-37, 1999.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 56
EP 59
PG 4
ER
PT J
AU Kabukcuoglu, F
Sungun, A
Senturk, AB
Evren, I
Ilhan, R
AF Kabukcuoglu, Fevziye
Sungun, Aysim
Senturk, Akan Billur
Evren, Ismail
Ilhan, Ridvan
TI Mixed Germ Cell Tumor of the Ovary with Sarcomatous Component
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Ovary; germ cell; sarcoma
ID Ovary; germ cell; sarcoma
AB Germ cell tumors constitute a very complicated group of tumors of the ovary and their histogenesis is not yet clarified. Besides their histological heterogeneity, sarcomatous areas have also been described. A right ovarian mass was found in a 23-year-old female, who was being treated in the hospital for miscarriage. Disseminated omental metastases were detected during abdominal laparotomy. Pathological examination of the dissected material revealed the tumor to be a mixed germ cell tumor (immature teratoma and dysgerminoma) with sarcomatous component. Areas resembling granulosa cell tumor were also encountered. This ovarian tumor with many different histopathological features is presented with a review of the literature. The importance of thorough sampling in determining the type and extent of the malignant components is also emphasized due to their direct relation with the prognosis.
C1 [Kabukcuoglu, Fevziye] Sisli Etfal Training and Research Hospital, Department of Pathology, Manastirli Ismail Hakki sk No:10/1 Dogancilar/UskudarIstanbul, Turkey.
[Sungun, Aysim] Sisli Etfal Training and Research Hospital, Department of Pathology, Manastirli Ismail Hakki sk No:10/1 Dogancilar/UskudarIstanbul, Turkey.
[Senturk, Akan Billur] Sisli Etfal Training and Research Hospital, Department of Pathology, Manastirli Ismail Hakki sk No:10/1 Dogancilar/UskudarIstanbul, Turkey.
[Evren, Ismail] Sisli Etfal Training and Research Hospital, Department of Pathology, Manastirli Ismail Hakki sk No:10/1 Dogancilar/UskudarIstanbul, Turkey.
[Ilhan, Ridvan] Sisli Etfal Training and Research Hospital, Department of Pathology, Manastirli Ismail Hakki sk No:10/1 Dogancilar/UskudarIstanbul, Turkey.
RP Kabukcuoglu, F (reprint author), Sisli Etfal Training and Research Hospital, Department of Pathology, Istanbul, Turkey.
EM fkabukcuoglu@hotmail.com
CR Ahmed T, Bosl GJ, Hadju S: Teratoma with malignant transformation in germ cell tumors in men. Cancer 56:860-863, 1985.
Akhtar M, Bakri Y, Rank F: Dysgerminoma of the ovary with rhabdomyosarcoma. Cancer 64:2309-2312, 1989.
Bolen JW: Mixed germ cell-sex cord stromal tumor. Am J Clin Pathol 75:565-573, 1981.
Kurman RJ, Norris HJ: Malignant mixed germ cell tumors of the ovary. A clinical and pathologic analysis of 30 cases. Obstet Gynecol 48:579-589, 1976.
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Nogales F: Germ cell tumors of the ovary, In: Obstetrical and Gynaecological Pathology., Eds: Fox H and Wells M): 4th ed, Churchill Livingstone, New York, 1995, pp 847-896.
Radford DM, Johnson FE, Janney CG: Sarcomatous change in a teratoma after treatment of testicular carcinoma. Cancer 68:395-399, 1991.
Rishi M, Howard LN, Bratthauer GL, Tavassoli FA: Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 2185:583- 589, 1997.
Talerman A: Germ cell tumors of the ovary. In Blaustein’s Pathology of the Female Genital Tract.(Ed: Kurman RJ), 4th ed, Springer-Verlag, New York 1994, pp 849-914.
Terrier-Lacombe MJ, Martinez-Madrigal F, Porta W, et al: Embryonal rhabdomyosarcoma arising in a mature teratoma of the testis: a case report. J Urol 143:1232-1234, 1990.
Ulbright TM: Germ cell Neoplasms of the testis. Am J Surg Pathol 17:1075-1091, 1993.
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Yamashita K, Yamoto M, Shikone T, et al: Production of inhibin A and inhibin B in human ovarian sex cord stromal tumors. Am J Obstet Gynecol 177: 1450-1457, 1997.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 60
EP 62
PG 3
ER
PT J
AU Cappello, F
Bellafiore, M
Bucchieri, F
Balsano, G
Palma, A
Zummo, G
AF Cappello, Francesco
Bellafiore, Marianna
Bucchieri, Fabio
Balsano, Giuseppe
Palma, Antonio
Zummo, Giovanni
TI Poorly Differentiated Synovial Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE synovial sarcoma; poorly differentiated synovial sarcoma; soft tissue tumors; calretinin; apoptosis
ID synovial sarcoma; poorly differentiated synovial sarcoma; soft tissue tumors; calretinin; apoptosis
AB Poorly differentiated synovial sarcoma is a rare soft tissue tumor. We studied a case arising in the pleural cavity of a young subject, characterised by the presence of spindle cell, small cell, and large epithelioid cell areas. We performed stains for mucosubstances and analysed the expression of cytokeratins 5/6, 7, 8, 18, 19, CEA, CD34, Ber-Ep4 and calretinin to characterize the phenotype of this neoplasm. We furthermore assessed immunohistochemically the presence of p53, Bcl-2, Bax and caspase 3, four apoptotic markers, to evaluate a relationship between apoptotic activity and the behaviour of this tumor. Our findings showed a strong presence of calretinin, p53 and Bcl-2 in all three areas. The possibility that poorly differentiated synovial sarcoma could be calretinin-positive was a new data, to our knowledge, and it could be of some importance in diagnostic pathology. Moreover, the negligible positivity for Bax and caspase 3 suggested that the minor role of programmed cell death could be one of the causes of the aggressive behaviour of this tumor. These data also suggest that the reduction of apoptotic phenomena in poorly differentiated synovial sarcoma could be considered one of the major mechanisms of tumoral growth.
C1 [Cappello, Francesco] University of Palermo, Institute of Pathological Anatomy, Via Alla Falconara 120, 90136 Palermo, Italy.
[Bellafiore, Marianna] University of Palermo, Institute of Human AnatomyPalermo, Italy.
[Bucchieri, Fabio] University of Palermo, Institute of Human AnatomyPalermo, Italy.
[Balsano, Giuseppe] University of Palermo, Institute of General and Endoscopic SurgeryPalermo, Italy.
[Palma, Antonio] University of Palermo, Institute of Human AnatomyPalermo, Italy.
[Zummo, Giovanni] University of Palermo, Institute of Human AnatomyPalermo, Italy.
RP Cappello, F (reprint author), University of Palermo, Institute of Pathological Anatomy, 90136 Palermo, Italy.
EM FRANCAPP@HOTMAIL.COM
CR Abenoza P, Manivel JC, Swanson PE, et al: Synovial sarcoma: ultrastructural study and immunohistochemical analysis by a combined peroxidase-antiperoxidase/avidin-biotin complex procedure. Hum Pathol 17:1107-1115, 1986.
Bissonnette RP, Echeverri F: Apoptotic cells induced by c-myc are inhibited by Bcl-2. Nature 359:552-554, 1992.
Bubendorf L, Sauter G, Moch H, et al: Prognostic significance of Bcl-2 in clinically localized prostate cancer. Am J Surg Pathol 148:1557-1565, 1996.
Chilosi M, Facchetti F, Dei Tos AP, et al: Bcl-2 expression in pleural and extrapleural solitary fibrous tumors. J Pathol 181:362-367, 1997.
Dei Tos AP, Wadden C, Calonje E: Immunohistochemical demonstration of glycoprotein p30/30 MIC2, CD99, in synovial sarcoma. A potential cause of diagnostic confusion. Applied immunohistochemistry 3:168-173, 1995.
Doglioni C, Dei Tos AP, Laurino L, et al: Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol 20:1037-1046, 1996.
Enzinger FM, Weiss SW: Soft tissue tumors. St. Louis, Mosby, 1995.
Fisher C: Ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors. Hum Pathol 17:996-1008, 1986.
Folpe AL, Schmidt RA, Chapman D, et al: Poorly differentiated synovial sarcoma. Immunohistochemical distinction from primitive neuroectodermal tumors and high grade malignant peripheral nerve sheath tumors. Am J Surg Pathol 22:673-682, 1998.
Gaertner E, Zeren EH, Fleming MV, et al: Biphasic synovial sarcoma arising in the pleural cavity. A clinicopathologic study of five cases. Am J Surg Pathol 138:505-513, 1991.
Hall PA, Levison DA: Biphasic tumor: clues to possible histogenesis in developmental processes. J Pathol 159:1-2, 1989.
Joensuu H, Pylkkanen L, Toikkanen S: Bcl-2 protein expression and long term survival in breast cancer. Am J Pathol 145:1191- 1198, 1994.
Kulig E, Jin L, Qian X, et al: Apoptosis in non-tumorous and neoplastic human pituitaries. Expression of the Bcl-2 family of proteis. Am J Pathol 154:767-774, 1999.
Lu QL, Abel P, Foster CS, et al: Bcl-2: role in epithelial differentiation and oncogenesis. Hum Pathol 27:102-110, 1996.
McPake CR, Tillman DM, Poquette CA, et al: Bax is an important determinant of chemosensitivity in pediatric tumor cell lines independent of Bcl-2 expression and p53 status. Oncol Res 10:235-244, 1998.
Meis-Kindblom JM, Stenman G, Kindblom LG: Differential diagnosis of small round cell tumors. Semin Diagn Pathol 13:213-241, 1996.
Nakanishi H, Ohsawa M, Naka N, et al: Immunohistochemical detection of Bcl-2 and p53 proteins and apoptosis in soft tissue sarcoma: their correlation with prognosis. Oncology 54:238- 244, 1997.
Nicholson AG, Goldstraw P, Fisher C: Synovial sarcoma of the pleura and its differentiation from other primary pleural tumors: a clinicopathological and immunohistochemical review of three cases. Histopathology 33:508-513, 1998.
Oltavi ZN, Milliman CL, Korsmeyer SJ: Bcl-2 hemerodimer in vivo with a conserved homologue, Bax, that accelerates programmed cell death. Cell 74:609-619, 1993.
Ordonez NG, Mahfouz SM, MacKay B: Synovial sarcoma: an immunohistochemical and ultrastructural study. Hum Pathol 21:733-749, 1990.
Ordonez NG: The immunohistochemical diagnosis of epithelial mesothelioma. Hum Pathol 30:313-323, 1999.
Salisbury JR, Isaacson PG: Synovial sarcoma: an immunohistochemical study. J Pathol 147:49-57, 1985.
Segers K, Ramael M, Singh Sk, et al: Immunoreactivity for Bcl- 2 protein in malignant mesothelioma and non-neoplastic mesothelium. Virchows Arch 424:631-634, 1994.
Singer S, Baldini EH, Demetri GD, et al: Synovial sarcoma: prognostic significance of tumor size, margin sesection and mitotic activity for survival. J Clin Oncol 14:1201-1208, 1996.
Suster S, Fisher C, Moran CA: Expression of Bcl-2 oncoprotein in benign and malign spindle cell tumors of soft tissue, skin, serosal surfaces and gastrointestinal tract. Am J Surg Pathol 22:863-872, 1998.
Tormanen U, Eerole AK, Rainio P, et al: Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res 55:595-602, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 63
EP 66
PG 4
ER
PT J
AU Girschick, JH
Klein, R
Scheurlen, GW
Kuhl, J
AF Girschick, J Hermann
Klein, Rudiger
Scheurlen, G Wolfram
Kuhl, Joachim
TI Cytogenetic and Histopathologic Studies of Congenital Supratentorial Primitive Neuroectodermal Tumors: A Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE PNET; primitive neuroectodermal tumor; brain neoplasm; congenital brain tumor; cytogenetic studies
ID PNET; primitive neuroectodermal tumor; brain neoplasm; congenital brain tumor; cytogenetic studies
AB Primitive neuroectodermal tumors (PNET) represent about 25% of primary central nervous system tumors in childhood, but congenital PNETs are rare. Cytogenetic studies and studies on molecular pathology have identified several genetic alterations in medulloblastoma, but molecular investigations on supratentorial PNETs are infrequent. We present a male newborn with a large congenital PNET of the right cerebral hemisphere and the molecular analysis of the tumor. Tumor tissue was investigated by routine histology and immunohistochemistry. Fluorescence in-situ hybridization was carried out on native tumor tissue to investigate deletions on chromosome 17p and to analyze c-Myc or N-Myc amplifications. Histologic examination revealed a primitive neuroectodermal tumor with massive extension covering almost the entire right hemisphere. Genetic analysis of the native tumor tissue of our patient excluded a deletion of chromosome 17p. An amplification of the c-Myc or N-Myc oncogene was absent using fluorescence in-situ hybridization. Despite unremarkable genetic analysis in our case prognosis was poor, suggesting that there are additional, yet unknown constitutional genetic aberrations in the pathogenesis of congenital supratentorial PNET.
C1 [Girschick, J Hermann] University of Wurzburg, Children’s Hospital, Josef-Schneider-Str. 2, D-97080 Wurzburg, Germany.
[Klein, Rudiger] University of Wurzburg, Institute of Pathology, Division of NeuropathologyWurzburg, Germany.
[Scheurlen, G Wolfram] University of Mannheim, Children’s HospitalMannheim, Germany.
[Kuhl, Joachim] University of Wurzburg, Children’s Hospital, Josef-Schneider-Str. 2, D-97080 Wurzburg, Germany.
RP Girschick, JH (reprint author), University of Wurzburg, Children’s Hospital, D-97080 Wurzburg, Germany.
EM Hermann.Girschick@mail.uni-wuerzburg.de
CR Cohen BH, Zeltzer PM, Boyett JM, et al: Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: A childrens cancer group randomized trial. J Clin Oncol 13:1687- 1696, 1995.
Cohen BH, Packer RJ: Chemotherapy for medulloblastomas and primitive neuroectodermal tumors. J Neurooncol 29:55-68, 1996.
Di Rocco C, Iannelli A, Papacci F, et al: Prognosis of medulloblastoma in infants. Child’s Nerv Syst 13:388-396, 1997.
Dirks PB, Harris L, Hoffmann HJ, et al: Supratentorial primitive neuroectodermal tumors in children. J Neurooncol 29:75- 84, 1996.
Evans AE, Jenkin RD, Sposto R, et al: The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 72:572-582, 1990.
Emadian SM, McDonald JD, Gerken SC, et al: Correlation of 17p loss with clinical outcome in medulloblastomas. Clin Cancer Res 2:1559-1564, 1996.
Giangaspero F, Bigner SH, Giordana MT, et al: Medulloblastoma. In: Pathology and Genetics of Tumors of the Nervous System., Eds: Kleihues P, Cavenee WK), International Agency for Research on Cancer, Lyon, 1997, pp. 96-103.
Haddad SF, Menezes AH, Bell WE: Brain tumors occuring before 1 year of age: a retrospective review of 22 cases in an 11-year period, 1977-1987). Neurosurgery 29:8-13, 1991.
Janisch W, Haas JF, Schreiber D, et al: Primary central nervous system tumors in stillborn and infants. Epidemiological considerations. J Neuroonocol 2:113-116, 1984.
Janss AJ, Yachnis AT, Silber JH, et al: Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors. Ann Neurol 39:481-489, 1996.
Joos S, Falk MH, Lichter P, et al: Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14, translocation separate c-Myc and the IgH locus up to several hundred kb. Hum Mol Genet 1:625-632, 1992.
Krischer JP, Ragab AH, Kun L: Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma. A pediatric oncology group study. J Neurosurg 74:905-909, 1991.
Lichter P, Tang CJ, Call K, et al: High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247:64-69, 1990.
Moriuchi S, Shimizu K, Miyao Y, et al: An immunohistochemical analysis of medulloblastoma and PNET with emphasis on NMyc protein expression. Anticancer Res 16:2687-2692, 1996.
Neumann E, Kalousek DK, Norman MG, et al: Cytogenetic analysis of 109 pediatric central nervous system tumors. Cancer Genet Cytogenet 71:40-49, 1993.
Ohgaki H, Eibl RH, Wiestler OD, et al: p53 mutations in nonastrocytic human brain tumors. Cancer Res 51:6202-6205, 1991.
Packer RJ, Sutton LN, Goldwein JW, et al: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74:433-440, 1991.
Raffel C, Gilles FE, Weinberg KI: Reduction to Homozygosity and Gene amplification in central nervous system primitive neuroectodermal tumors of childhood. Cancer Res 50:587-591, 1990.
Rorke LB, Trojanowski JQ, Lee VM: Primitive neuroectodermal tumors of the central nervous system. Brain Pathology 7:765- 784, 1997.
Rostomily RC, Bermingham-McDonogh O, Berger MS, et al: Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors. Cancer Res 57:3526-3531, 1997.
Scheurlen WG, Krauss J, Kuhl J: No preferential loss of one parental allele of chromosome 17p13.3 in childhood medulloblastoma. Int J Cancer 63:372-374, 1995.
Scheurlen W, Seranski P, Mincheva A, et al: High resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors, PNET, reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in band 17p11.2. Genes Chromosomes Cancer 18:50-58, 1997.
Scheurlen WG, Schwabe GC, Joos S, et al: Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome. J Clin Oncol 16:2478-2485, 1998.
Scheurlen WG, Sorensen N, Roggendorf W, et al: Molecular analysis of medulloblastomas occuring simultaneously in monocygotic twins. Eur J Pediatr 155:880-884, 1996.
Schutz BR, Scheurlen W, Krauss J, et al: Mapping of chromosomal gains and losses in primitive neuroectodermal tumors by comparative genomic hybridization. Genes Chromosomes Cancer 16:196-203, 1996.
Tait DM, Thornton-Jones H, Bloom HJ, et al: P: Adjuvant chemotherapy for medulloblastoma: the first multi-center control trial of the International Society of Pediatric Oncology, SIOP I). Eur J Cancer 26:464-469, 1990.
Tomita T, McLone DG, Yasue M: Cerebral primitive neuroectodermal tumors in childhood. J Neurooncol 6:233-243, 1988.
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Wilgenbus K, Mincheva A, Korn B: IRS-long range PCR: a simple method for amplification of human genomic DNA from complex sources. Meth Mol Cell Biol 5:214-221, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 67
EP 71
PG 5
ER
PT J
AU Repassy, LD
Csata, S
Sterlik, G
Ivanyi, A
AF Repassy, L Denes
Csata, Sandor
Sterlik, Gabor
Ivanyi, Andras
TI Giant Adrenal Myelolipoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adrenal gland; tumor; myelolipoma
ID adrenal gland; tumor; myelolipoma
AB Authors present a case of giant adrenal myelolipoma, where the tumor was hormonally inactive but caused abdominal and flank pain. The huge tumor, a 20x18x10 cm mass, was surgically removed. The ipsilateral kidney was preserved.
C1 [Repassy, L Denes] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1., H-1096 Budapest, Hungary.
[Csata, Sandor] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1., H-1096 Budapest, Hungary.
[Sterlik, Gabor] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1., H-1096 Budapest, Hungary.
[Ivanyi, Andras] Municipal Hospital, Del-Pest, Department of PathologyBudapest, Hungary.
RP Repassy, LD (reprint author), Saint Stephen Hospital, Department of Urology, H-1096 Budapest, Hungary.
CR Albala DM, Chung CJ, Sueoka BL, et al: Hemorrhagic myelolipoma of adrenal gland after blunt trauma. Urology 38:559, 1991.
Meaglia JP, Schmidt JD: Natural history of an adrenal myelilipoma. J Urol 147:1089, 1992.
Goldman HB, Howard RC, Patterson L: Spontenaous retroperitoneal hemorrhage from a giant adrenal myelolipoma. J Urol 155:639, 1995.
Lam KY: Lipomatous tumors of the adrenal gland. J Urol Pathol 3:95, 1995.
Gould JD, Mitty HA, Pertsemlidis D, et al: Adrenal myelilipoma: diagnosis by fine needly aspiration. Am J Radiol 148:921, 1987.
Bennett BD, McKenna RJ, Hough AI: Adrenal myelilipoma associated with Cushing’s disease. Am J Clin Pathol 73:443, 1980.
Olsson CA, Krane RJ, Klugo RC, et al: Adrenal myelolipoma. Surgery 73:665-670, 1973.
Desai SB, Dourmashkin L, Kabakow BR, et al: Myelolipoma of the adrenal gland: case report. literature review and analysis of diagnostic features. Mt Sinai J Med. 46:155-159, 1979.
Vick CW, Zeman RK, Mannes E, et al.: Adrenal myelolipoma: CT and ultrasound findings. Urol Radiol 6:7-13, 1984.
Newmann P, Silen W: Myelolipoma of the adrenal gland. Arch Surg 97:637, 1968.
Gierke E: Ueber Knochenmarksgewebe in der Nebenniere. Beitr Path Anat. 7:311, 1905.
Oberling, C: Les formations myelo-lipomateuses. Bull Assoc Franc Cancer 18:234, 1929.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 72
EP 73
PG 2
ER
PT J
AU Sharma, ChM
Vaish, S
Arora, R
Gaikwad, S
Sarkar, Ch
AF Sharma, Chand Mehar
Vaish, Sandeep
Arora, Reena
Gaikwad, Sailesh
Sarkar, Chitra
TI Composite Pituitary Adenoma and Intrasellar Tuberculoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adenoma; endocrine; pituitary gland; sella; tuberculoma
ID adenoma; endocrine; pituitary gland; sella; tuberculoma
AB Tuberculous involvement of the pituitary gland is rare. We report a unique case of a composite lesion consisting of pituitary adenoma and intrasellar tuberculoma. A 24-year-old lady presented with features of acromegaly and amenorrhea. Serum growth hormone levels were found to be raised. Radiological investigations were consistent with a pituitary adenoma. Decompression of the lesion was done through trans-sphenoidal approach. Histological examination revealed a growth hormone secreting pituitary adenoma in association with a granulomatous lesion suggesting of pituitary tuberculoma. No other evidence of tuberculosis was found in the brain or spinal cord. This type of dual pathology has been reported only once in the earlier literature.
C1 [Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Vaish, Sandeep] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Arora, Reena] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Gaikwad, Sailesh] All India Institute of Medical Sciences, Department of NeuroradiologyNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarch@medinst.ernet.in
CR Ashkan K, Papadopoulos MC, Casey AT, et al: Sellar tuberculoma: report of twocase. Acta Neurochir, Wien, 139: 523-525, 1997.
Bhagwati SN: Intracranial tuberculoma. Neurology India 34:161-163, 1996.
Brooks MH, Dunlao JS, Bronsky D, et al: Hypophysial tuberculoma with hypopituitarism. Am J Med 54:777-781, 1973.
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Eckland DJA, O’ Neil JH, Lightman SL: A pituitary tuberculoma. J Neurol Neurosurg Psychia 50:360-61, 1987.
Esposito V, Fraioli B, Ferrante L, Palma L: Intrasellar tuberculoma: case report. Neurosurg 21:721-723, 1987.
Gazioglu N, AK II, Oz B, et al: Silent pituitary tuberculoma associated with pituitary adenoma. Act Neurochir, Wien, 141:785-786, 1999.
Ghosh S, Chandy MJ: Intrasellar tuberculoma case report. Clin Neurol Neurosurg 94:251-252, 1992.
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Pereira J, Vaz R, Carvalho D, et al: Thickening of pituitary stalk: A finding suggestive of intrasellar tuberculoma? Case report. Neurosurg 36:1013-1016, 1995.
Petrossians P, Delvenne P, Flandroy P, et al: An unusual pituitary pathology. J Clin Endo Metabolism 83:3454-3459, 1998.
Ranjan A, Chandy MJ: Intrasellar tuberculoma. Brit J Neurosurg 8:179-185, 1994.
Rohmer V, Chanson P, Dupas B, et al: Intrasellar non-adenomatous expansive process. Ann endocrinol, Paris, 58:11-19, 1997.
Sharma MC, Arora R, Mahapatra AK, et al: Intrasellar tuberculoma – an enigmatic pituitary infection: a series of 18 cases. Clin Neurol and Neurosurg 102:72-77;2000.
Taparia SC, Tyagi G, Singh AK, et al: Sellar tuberculoma. J Neurol Neurosurg Psychiatr 55:629, 1992.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2001
VL 7
IS 1
BP 74
EP 76
PG 3
ER
PT J
AU Timar, J
Dome, B
Fazekas, K
Janovics,
Paku, S
AF Timar, Jozsef
Dome, Balazs
Fazekas, Karoly
Janovics, Agnes
Paku, Sandor
TI Angiogenesis-Dependent Diseases and Angiogenesis Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE angiogenesis; diseases; pro-angiogenesis; anti-angiogenesis
ID angiogenesis; diseases; pro-angiogenesis; anti-angiogenesis
AB The discovery of the molecular mechanisms of physiological vasculogenesis and pathological angiogenesis helped to recognize two classes of diseases: one where the therapeutic angiogenesis can repair the tissue damages (arteriosclerosis, myocardial infarction, limb ischemia) and the other one where inhibition of pathological angiogenesis can cure the disease or delay its progression (retinopathies, benign and malignant angiogenic tumors, progression of malignant tumors). Although there are an exponentially growing number of new synthetic molecules characterized mainly by antiangiogenic properties, the discovery of a large battery of natural pro- and anti-angiogenic factors suggests that this may provide a more physiological approach to treat both class of angiogenesis-dependent diseases in the near future.
C1 [Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H1122 Budapest, Hungary.
[Dome, Balazs] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Fazekas, Karoly] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H1122 Budapest, Hungary.
[Janovics, Agnes] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H1122 Budapest, Hungary.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H1122 Budapest, Hungary.
CR Albini A, Benelli R, Presta M, et al: HIV-tat protein is a heparin binding angiogenic growth factor. Oncogene 12:289-297, 1996.
Bae DG, Gho YS, Yoon WH, et al: Arginic-rich anti-vascular endothelial growth factor peptides inhibit tumor growth and metastasis by blocking angiogenesis. J Biol Chem 275:13588- 13596, 2000.
Bowder T, Folkman J, Pirie-Shepherd S: The hemostatic system as a regulator of angiogenesis. J Biol Chem 275:1521-1524, 2000.
Brown JM: Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Molecular Medicine Today 6:157-162, 2000.
Bussolino F, Albini A, Camussi G, et al: Role of soluble mediators in angiogenesis. Eur J Cancer 32A:2401-2412, 1996.
Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nature Medicine 6:389-395, 2000.
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Elicieri BP, Cheresh DA:The role ofav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 103:1227-1230, 1999.
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Holmgren L, O’Reilly MS, Folkman J: Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149-153, 1995.
Isner JM, Asahara T: Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 103:1231-1235, 1999.
Jacobson BS: Hereditary hemorrhagic telangiectasia a model for blood vessel growth and enlargement. Am J Path 156:737- 742, 2000.
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Kerbel RS: Tumor angiogenesis: past, present and the near future. Carcinogenesis 21:505-515, 2000.
Lee P, Wang CC, Adamis AP: Ocular neovascularization: an epidemiologic review. Surv Ophthalmol 43:245-269, 1998.
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Maniotis AJ, Folberg R, Hess A, et al: Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739-752, 1999.
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O’Reilly MS, Boehm T, Shing Y, et al: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277-285, 1997.
Paku S: Current concepts of tumor-induced angiogenesis. Pathol Oncol Res 4:62-75, 1998.
Pribluda VS, Gubish ER, LaVallee, TM. Jr, et al: Methoxyestradiol: An endogenous antiangiogenic and antiproliferative drug candidate. Cancer Metast Reviews 19:173-179, 2000.
Sasisekharan R, Moses MA, Nugent MA, et al: Heparinase inhibits neovascularization. Proc Nat Acad Sci USA 91:1524-1528, 1994.
Schiller J: Early trials of antiangiogenic agents. Anticancer Agents in Oncology 15:3-10, 1999.
Schlaeppi J-M, Wood JM: Targeting vascular endothelial growth factor, VEGF, for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine-kinase inhibitors. Cancer Metastasis Rev 18:473-381, 1999.
Semenza GL: HIF-1: Using two hands to flip the angiogenic switch. Cancer Metast Reviews 19:59-65, 2000.
Stephens TD, Fillmore BJ: Hypothesis: Thalidomine embryopathy- proposed mechanism of action. Teratology 61:189-195, 2000.
Stetler-Stevenson WG: Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103:1237-1241, 1999.
Thompson WD, Li WW, Maragoudakis M: The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies. J Pathol 190:330-337, 2000.
Timar J, Toth J: Tumor sinuses – vascular channels. Pathol Oncol Res 6:83-86, 2000.
Venkov CD, Rankin AB, Vaughan DE: Identification of authentic estrogen receptor in cultured endothelial cells. A potential mechanism for steroid hormone regulation of endothelial function. Circulation 94:727-733, 1996.
Xu C, Lee S, Singh TM, et al: Molecular mechanisms of aortic wall remodeling in response to hypertension. J vasc Surg 33:570-578, 2001.
Yeh ChH, Peng H-Ch, Huang T-F: Accutin, a new desintegrin, inhibits angiogenesis in vitro and in vivo by acting as integrinavb3 antagonist and inducing apoptosis. Blood 92:3268-3276, 2000.
Zhang M, Volpert O, Shi YH, et al: Maspin is an angiogenesis inhibitor. Nature Medicine 6:196-199, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 85
EP 94
PG 10
ER
PT J
AU Petak, I
Houghton, AJ
AF Petak, Istvan
Houghton, A Janet
TI Shared Pathways: Death Receptors and Cytotoxic Drugs in Cancer Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE apoptosis; tumor; death receptor; Fas; drug; p53
ID apoptosis; tumor; death receptor; Fas; drug; p53
AB Death ligands (TNF, FasL, TRAIL) and their respective death receptor signaling pathways can be used to induce tumor cells to undergo apoptosis. Chemotherapeutic drugs can induce apoptosis and the upregulation of death ligands or their receptors. Downstream events following cytotoxic stress-induced DNA damage and the signaling pathways that lead to the induction of apoptosis may be either dependent or independent of death receptor signaling. The involvement of the Fas signaling pathway in chemotherapy-induced apoptosis has been the most extensively studied, with the current emergence of information on the TRAIL signaling pathway. Fas-mediated and chemotherapy-induced apoptosis can converge at the level of the receptor, FasL, DISC formation, activation of the initiator caspase-8, at the level of the mitochondria, or at the level of downstream effector caspase activation. Convergence is influenced by the specific form of DNA damage, the cellular environment, and the specific pathway(s) by which death receptor-mediated or drug-mediated apoptosis are induced. This review discusses the different levels of interaction between signaling pathways in the different forms of cell death.
C1 [Petak, Istvan] St. Jude Children's Research Hospital, Department of Hematology-Oncology, Division of Experimental Hematology, 332 North Lauderdale, 38105 Memphis, TN, USA.
[Houghton, A Janet] St. Jude Children's Research Hospital, Department of Hematology-Oncology, Division of Experimental Hematology, 332 North Lauderdale, 38105 Memphis, TN, USA.
RP Houghton, AJ (reprint author), St. Jude Children's Research Hospital, Department of Hematology-Oncology, Division of Experimental Hematology, 38105 Memphis, USA.
EM janet.houghton@stjude.org
CR Ashkenazi A, Dixit VM: Death receptors: Signaling and modulation. Science 281:305-108, 1998.
Ware CF, VanArsdale S, VanArsdale TL: Apoptosis mediated by the TNF-related cytokine and receptor families. J Cell Biochem 60:47-55, 1996.
McGeehan GM, Becherer JD, Bast RCJr, et al: Regulation of tumor necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 370:558-561, 1994.
Tanaka M, Itai T, Adachi M, et al: Downregulation of Fas ligand by shedding. Nature Med 4:31-36, 1998.
Kayagaki N, Kawasaki A, Ebata T, et al: Metalloproteinasemediated release of human Fas ligand. J Exp Med 182:1777- 1783, 1995.
Ashkenazi A, Dixit VM: Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255-260, 1999.
Nagata S, Golstein P: The Fas death factor. Science 276:1449, 1995.
Arai H, Gordon D, Nabel EG, et al: Gene transfer of Fas ligand induces tumor regression in vivo. Proc Natl Acad Sci USA 94:13862-13867, 1997.
French LE, Hahne M, Viard I, et al: Fas and Fas ligand in embryos and adult mice: ligand expression in several immuneprivileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol 133:335-343, 1996.
Moller P, Koretz K, Leithauser F, et al: Expression of Apo-1, CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium. Int J Cancer 57:371- 377, 1994.
Pitti RM, Marsters SA, Lawrence DA, et al: Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 396:699-703. 1998.
Itoh N, Yonehara S, Ishii A, et al: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66:233-243, 1991.
Boldin MP, Varfolomeev EE, Pancer Z, et al: A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem 270:7795-7798, 1995.
Chinnaiyan AM, O’Rourke K, Tewari M, et al: FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505-512, 1995.
Boldin MP, Goncharov TM, Goltsev YV, et al: Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO1 and TNF receptor-induced cell death. Cell 85:803- 815, 1996.
Medema JP, Scaffidi C, Kischkel FC, et al: FLICE is activated by association with the CD95 death-inducing signaling complex, DISC). EMBO J 16:2794-2804, 1997.
Muzio M, Chinnaiyan AM, Kischkel FC, et al: FLICE a novel FADD-homologous ICE/CED-3-like protease is recruited to the CD95, Fas/Apo-1, death-inducing signaling complex. Cell 85:817-827, 1996.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 95
EP 106
PG 12
ER
PT J
AU Banhegyi, G
Mandl, J
AF Banhegyi, Gabor
Mandl, Jozsef
TI The Hepatic Glycogenoreticular System
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE glycogen; glycogenolysis; endoplasmic reticulum; glucuronidation; ascorbate; glucose-6-phosphatase
ID glycogen; glycogenolysis; endoplasmic reticulum; glucuronidation; ascorbate; glucose-6-phosphatase
AB One of the major liver functions is the ability of hepatocytes to store glucose in the form of glycogen for various purposes. Beside glucose production and secretion, the synthesis of glucuronides and ascorbate has been reported to be dependent on the extent of the glycogen stores and on the rate of glycogenolysis in the liver. It is common that the final steps of these pathways are catalysed by intraluminally orientated enzymes of the endoplasmic reticulum, which are supported by transporters for the permeation of substrates and products. On the basis of the close morphological and functional proximity of glycogen, glycogen-dependent pathways and the (smooth) endoplasmic reticulum we propose to use the term ''glycogenoreticular system'' for the description of this export-orientated hepatocyte-specific metabolic unit.
C1 [Banhegyi, Gabor] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H1444 Budapest, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H1444 Budapest, Hungary.
RP Mandl, J (reprint author), Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, H1444 Budapest, Hungary.
EM mandl@puskin.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 107
EP 110
PG 4
ER
PT J
AU Croce, VM
Price, RM
Segal-Eiras, A
AF Croce, Virginia Maria
Price, R Mike
Segal-Eiras, Amada
TI Association of a alpha1 Acidic Glycoprotein and Squamous Cell Carcinoma of the Head and Neck
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck cancer; alpha1 acidic-glycoprotein; disease stage
ID Head and neck cancer; alpha1 acidic-glycoprotein; disease stage
AB Serum from patients with different malignancies contain an abnormal concentration of a a1-acidic-glycoprotein (AAG) and also, increased levels of AAG are associated with the presence of tumor mass. In the present report, serum levels of AAG were measured by radial immunodiffusion in squamous cell carcinoma of the head and neck (SCCHN) patients taking into account disease status parameters such as tumor localization, stage and extension of disease. Immunohistochemical methods, SDS-PAGE and Western-blotting were employed to study the expression of AAG and a carbohydrate related antigen (sialyl Lewis x) in tumor tissues and derived fractions. AAG showed abnormal levels in 7/15 oral cavity tumor patients’ sera, 2/5 oropharynx and 5/10 larynx tumors; increased AAG serum levels belonged to patients with disseminated disease. On the other hand, the presence of AAG and sialyl Lewis x were demonstrated in carcinoma cells and in derived fractions from tumor tissues belonging to patients with elevated AAG serum levels. In the present study, we have found elevated levels of AAG in serum samples from SCCHN patients; these neoplastic cells are capable to express AAG.
C1 [Croce, Virginia Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120, 1900 La Plata, Argentina.
[Price, R Mike] University of Nottingham, School of Pharmaceutical Sciences, Cancer Research LaboratoriesNottingham, UK.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120, 1900 La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), 1900 La Plata, Argentina.
EM as-eiras@netverk.com.ar
CR Bennett M, Schmid K: Immunosuppression by human plasma a1 acid glycoprotein: importance of the carbohydrate moiety. Proc Natl Acad Sci USA 77:6109-6114, 1980.
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Croce MV, Segal-Eiras A: Identification of acute–phase proteins, APP, in circulating immune complexes, CIC, in esophageal cancer patients’ sera. Cancer Invest 4:421-426, 1997.
Croce MV, Colussi AG, Price M, et al: An immunohistopathological characterization of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma, HLMC, xenograft. Pathol Oncol Res 4:259-266, 1998.
Chandrasekaran EV, Davila M, Nixon D, et al: Structures of oligosaccharide chains of two forms of a1 acidic glycoprotein purified from liver metastases of lung, colon and breast tumors. Cancer Res 44:1557-1567, 1984.
Cheresh DA, Haynes D, Distasio JA: Interaction of an acute phase reactant a1 acid glycoprotein [orosomucoid] with the lymphoid cell surface a model for non-specific immune suppression. Immuno 51:541-547, 1984
Dage JL, Ackermann BL, Halsall HB: Site localization of sialyl Lewisx antigen ona1 acid glycoprotein by high performance liquid chromatography-electrospray mass spectometry. Glycobiol 8:755-760, 1998.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 111
EP 117
PG 7
ER
PT J
AU Magyarlaki, T
Buzogany, I
Kaiser, L
Sukosd, F
Dobronte, R
Simon, B
Fazekas, A
Nagy, J
AF Magyarlaki, Tamas
Buzogany, Istvan
Kaiser, Laszlo
Sukosd, Farkas
Dobronte, Robert
Simon, Barbara
Fazekas, Attila
Nagy, Judit
TI Prognostic Histological and Immune Markers of Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE renal cell carcinoma; histology; immunohistochemistry; immunotherapy; clinicopathology
ID renal cell carcinoma; histology; immunohistochemistry; immunotherapy; clinicopathology
AB Recent development on the fields of molecular genetics and immunology of human renal cell carcinoma (RCC) have resulted in more successful treatment of advanced and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the initial tumor staging of RCC patients to achieve better patient selection for immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg histological classification, graded, Robson staged, immune treated (Interferon-a a+ Vinblastin or Broncho-Waxom/Decaris) were followed-up clinically for 36 months. Tumor immunity markers by immunohistochemistry of tumor infiltrating lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic status (related with the stage and grade) determined the clinical outcome (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based histological classification, grade, stage and metastatic status parameters together with some tumor immunity parameters (TIL, TIC) can predict the success of immunotherapy of RCC patients.
C1 [Magyarlaki, Tamas] University of Pecs, Institute of Biochemistry and Medical Chemistry, Ifjusag utja 13.Pecs, Hungary.
[Buzogany, Istvan] University of Pecs, Department of UrologyPecs, Hungary.
[Kaiser, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Sukosd, Farkas] University of Pecs, Department of PathologyPecs, Hungary.
[Dobronte, Robert] University of Pecs, Institute of Biochemistry and Medical Chemistry, Ifjusag utja 13.Pecs, Hungary.
[Simon, Barbara] University of Pecs, Institute of Biochemistry and Medical Chemistry, Ifjusag utja 13.Pecs, Hungary.
[Fazekas, Attila] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Nagy, Judit] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
RP Magyarlaki, T (reprint author), University of Pecs, Institute of Biochemistry and Medical Chemistry, Pecs, Hungary.
EM kellerm@apacs.pote.hu
CR Angevin E, Kreme, F, Gaudin C, et al: Analysis of T-cell immune response in renal cell carcinoma: polarisation to type 1-like differentiation pattern, clonal T-cell expansion and tumor-specific cytotoxicity. Int J Cancer 72:431-440, 1997.
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Buszello H, Ackermann R:Immunohistochemical studies on the expression of HLA Class I antigen in renal cell carcinoma: comparison of primary and metastatic tumor tissue. Eur Urol 25:158-163, 1994.
Buzogany I, Czvalinga I, Gotz F: Ambulanter vegzett interferon mono- es kombinacios terapia eredmenye elorehaladott vesedaganat eseten. Orv Hetil 138:67-70, 1997.
Chang AE, Aruga A, Cameron MJ, et al: Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J Clin Oncol 15:796- 807, 1997.
Corless CL, Kibel AS, Iliopoulos O, et al: Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum Pathol 28:459-463, 1996.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 118
EP 124
PG 7
ER
PT J
AU Khan, E
Mapara, Z
Khan, Sh
Naveeda, A
Siddiqui, T
Pervez, Sh
AF Khan, Enver
Mapara, Zohair
Khan, Shaista
Naveeda, Arshad
Siddiqui, Tariq
Pervez, Shahid
TI DNA Ploidy Analyses in 218 Consecutive Pakistani Breast Cancer Patients: Does it Add Anything?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA ploidy; breast carcinoma; Pakistan
ID DNA ploidy; breast carcinoma; Pakistan
AB An analysis was made to evaluate the significance of DNA ploidy in the biology and prognosis of breast carcinoma. This was done by estimating the correlation of DNA ploidy with other established prognostic markers of breast cancer, namely tumor size, tumor grade, lymph node metastasis and S-phase fraction. From 1995 up to year 2000 ploidy analysis was performed on 218 consecutive cases of infiltrating breast carcinoma by flow cytometry using formalin fixed paraffin embedded material. From the laboratory record, data regarding other pathological variables was retrieved. No correlation could be found between DNA ploidy and tumor grade, nor could there be found a correlation with tumor size. For lymph node metastasis there was a significant difference between the proportion of aneuploids and diploids having metastasis in more than 4 lymph nodes. However, no significant difference was found in axillary lymph node positive and negative groups when number of positive lymph nodes was not taken into account. The mean value of S-phase fraction for the aneuploids and the diploids was also insignificantly different. In conclusion DNA ploidy alone did not add much to predict tumor behaviour in terms of known pathologic variables.
C1 [Khan, Enver] The Aga Khan University, Department of Pathology and MicrobiologyKarachi, Pakistan.
[Mapara, Zohair] The Aga Khan University, Department of Pathology and MicrobiologyKarachi, Pakistan.
[Khan, Shaista] The Aga Khan University, Department of SurgeryKarachi, Pakistan.
[Naveeda, Arshad] The Aga Khan University, Department of Pathology and MicrobiologyKarachi, Pakistan.
[Siddiqui, Tariq] The Aga Khan University Medical Centre, Department of MedicineKarachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and MicrobiologyKarachi, Pakistan.
RP Pervez, Sh (reprint author), The Aga Khan University, Department of Pathology and Microbiology, Karachi, Pakistan.
EM shahid.pervez@aku.edu
CR Naila Z, Azhar M, Parveen A, et al: Pattern of malignant tumors in Karachi- is it different? JCPSP 10:338-341, 2000.
Bhurgri Y, Bhurgi A, Hassan SH, et al: Cancer Incidence in Karachi, Pakistan: first results form Karachi Cancer Registry. Int J Cancer 85:325-329, 2000.
Brower ST, Tartter PI, Ahmed S, et al: Proliferative indices and oncoprotein expression in benign and malignant breast biopsies. Ann Surg Oncol 2:416-423, 1995.
Utada Y, Yoshimoto M, Kasumi F, et al: Relationship between DNA ploidy and survival in breast cancer. Gan To Kagaku Ryoho 25 Suppl: 431-435, 1998.
Camplejohn RS, Ash CM, Gillett CE, et al: The prognostic significance of DNA flow cytometry in breast cancer: results from 881 patients treated in a single centre. Br J Cancer 71:140-145, 1995.
Wong SW, Rangan AM, Bilous AM, et al: The value of S-phase and DNA ploidy analysis as prognostic markers for node-negative breast cancer in the Australian setting. Pathology 31:90-94, 1999.
Shiao YH, Chen VW, Lehmann HP, et al: Patterns of DNA ploidy and S-phase fraction associated with breast cancer survival in blacks and whites. Clin Cancer Res. 3:587-592, 1997.
Chen CM, Chang HT, Mok KT, et al: Analysis of prognostic factors in Chinese women with breast cancer in southern Taiwan. Chung Hua I Hsueh Tsa Chih Taipei 62:717-723, 1999.
Krieger N, van den Eeden SK, Zava D, et al: Race/ethnicity, social class and prevalence of breast cancer prognostic biomarkers: A study of white, black, and Asian women in the San Francisco bay area. Ethn Dis 7:137-149, 1997.
Stanton PD, Cooke TG, Oakes SJ, et al: Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer. Br J Cancer 66:925-929, 1992.
Stal O, Brisfors A, Carstensen J, et al: Relationships of DNA ploidy, S-phase fraction and hormone receptor status to tumor stage in breast cancers detected by population screening. The South-East Sweden Breast Cancer Group. Int J Cancer 51:28- 33, 1992.
Feichter GE, Mueller A, Kaufmann M, et al: Correlation of DNA flow cytometric results and other prognostic factors in primary breast cancers. Int J Cancer 41:823-828, 1988.
Kallioniemi OP, Blanco G, Alavaikko M, et al: Improving the prognostic value DNA flow cytometry in Breast Cancer by combining DNA index and S-Phase fraction. Cancer 62:2183- 2190, 1988. 13. Dressler LG, Seamer LC, Owens MA, et al: A flow cytometry and prognostic factors in 1331 frozen breast cancer specimens. Cancer 61:420-427, 1988.
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Dittadi R, Calderazzo F, Cabrelle A, et al:C-erbB-2/neu protein expression, DNA ploidy and S phase in breast cancer. Cell Prolif 29:403-412, 1996.
Wenger CR, Beardslee S, Owens MA, et al: DNA ploidy, Sphase, and steroid receptors in more than 127,000 breast cancer patients. Breast Cancer Res Treat 28:9-20, 1993.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 125
EP 128
PG 4
ER
PT J
AU Tenderenda, M
Rutkowski, P
Jesionek-Kupnicka, D
Kubiak, R
AF Tenderenda, Micha
Rutkowski, Piotr
Jesionek-Kupnicka, Dorota
Kubiak, Robert
TI Expression of CD34 in Gastric Cancer and its Correlation with Histology, Stage, Proliferation Activity, p53 Expression and Apoptotic Index
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD 34 immunostaining; gastric cancer
ID CD 34 immunostaining; gastric cancer
AB The formation of new blood vessels is essential for tumor growth and progression. Until today there are only few studies of the immunohistochemical assessment of angiogenesis in gastric cancer by the evaluation of the expression of CD34 antigen. The aim of this study was to analyze the relationship between microvessel density (MVD) expressed as the mean count of CD34 immunostained vessels and clinicopathologic features of gastric tumors (the histological type according to the Lauren classification, tumor grade – G; presence of lymph node metastases – N; depth of tumor invasion; stage of disease (UICC-AJCC 1988–1992), p53 expression, tumor cell proliferative activity described as the Ki67 labelling index and apoptotic index of tumor cells – TUNEL method). We assessed formalin-fixed, paraffin-embedded tissue samples obtained during potentially radical gastrectomy from 58 patients with primary gastric adenocarcinoma. The representative tissue blocks from each tumor were used for the immunohistochemical assay and examined by two pathologists independently. MVD was counted in five tumor areas of the most intensive neovascularization (x 200 field by light microscopy) and the mean counts were recorded. The mean MVD (CD34 expression value±SD) in this study was 43,15±19,8 per x 200 field. The study demonstrated the statistically significant correlation between MVD and two main histological parameters: tumor grading (p < 0.001) and tumor histological type according to Lauren’s classification (p<0.05). In well – and moderately – differentiated tumors (G1/2) MVD was significantly lower in comparison to the group of poorly differentiated cancer – G3 (mean value: 31,62 vs. 49,89). MVD was higher in diffuse type of gastric cancer comparing to intestinal type (50.05±19,03 vs. 39.17±20,09). However, the authors failed to find a significant correlation between MVD and other investigated histopathological features in malignant gastric tumors. The close relationship between CD34 immunostaining, gastric cancer tumor vascularity and main histological parameters was shown in this study. It can be stated that analysis of expression of angiogenesis in gastric cancer may be helpful for better estimation of hematogenous recurrence and the selection of the group of patients for adjuvant antiangiogenic treatment.
C1 [Tenderenda, Micha] Medical University of Lodz, Department of Oncological SurgeryLodz, Poland.
[Rutkowski, Piotr] M. Sklodowska-Curie Memorial Cancer Center-Institute, Department of Soft Tissue/Bone Tumors, Roentgena Str. 5, 02-781Warsaw, Poland.
[Jesionek-Kupnicka, Dorota] Medical University of Lodz, Department of PathologyLodz, Poland.
[Kubiak, Robert] Medical University of Lodz, Department of PathologyLodz, Poland.
RP Rutkowski, P (reprint author), M. Sklodowska-Curie Memorial Cancer Center-Institute, Department of Soft Tissue/Bone Tumors, Warsaw, Poland.
EM rutkowskip@coi.waw.pl
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Tanigawa N, Amaya H, Matsumura M, et al: Tumor angiogenesis and mode of metastasis in patients with colorectal cancer Cancer Res 57:1043-1046, 1997.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 129
EP 134
PG 6
ER
PT J
AU Gharagozloo, S
Khoshnoodi, J
Shokri, F
AF Gharagozloo, Soheila
Khoshnoodi, Jalal
Shokri, Fazel
TI Hepatitis C virus Infection in Patients with Essential Mixed Cryoglobulinemia, Multiple Myeloma and Chronic Lymphocytic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatitis C virus; Lymphoproliferative disorders; Anti-HCV antibody
ID Hepatitis C virus; Lymphoproliferative disorders; Anti-HCV antibody
AB Increased prevalence of HCV infection in some lymphoproliferative diseases has been recently reported. In the present study, the frequency of anti-HCV antibody (Ab) together with hepatitis B surface (HBs) antigen (Ag) and anti-HBs Ab were determined in 42, 45 and 23 patients with essential mixed cryoglobulinemia (EMC), multiple myeloma (MM) and B-cell chronic lymphocytic leukemia (B-CLL), respectively. Thirty hospitalized patients with chronic rheumatoid arthritis (RA) were also included as a control. Specific antibodies to HCV antigens were detected by enzyme linked immunosorbent assay (ELISA) and positive results were confirmed by a recombinant immunoblot assay (RIBA). Our results demonstrated anti-HCV positivity in 69%, 11% and 4.3% of the EMC, MM and B-CLL samples tested, respectively. None of the RA patients were found to be anti-HCV positive. No significant differences were observed between the patients’ groups regarding the frequency of HBs Ag and anti-HBs Ab. Considering the low incidence of HCV infection in the control group and the normal population, these results confirm and extend previous reports on the possible role of HCV infection in the etiology of EMC and further suggest involvement of this virus in a subset of MM.
C1 [Gharagozloo, Soheila] School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
[Khoshnoodi, Jalal] School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
[Shokri, Fazel] School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
RP Shokri, F (reprint author), School of Medical Sciences, Tarbiat Modarres University,, Department of Immunology, 14155 Tehran, Iran.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 135
EP 139
PG 5
ER
PT J
AU Gati, I
Leel-Ossy, L
AF Gati, Istvan
Leel-Ossy, Lorant
TI Heat Shock Protein 60 in Corpora Amylacea
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HSP 60; corpora amylacea; neurological disease
ID HSP 60; corpora amylacea; neurological disease
AB Heat shock protein 60 representation in the corpora amylacea of the brain was investigated in five different neurological diseases. In the cases with cerebral infarct, amyotrophic lateral sclerosis, multiple sclerosis, acute disseminated encephalomyelitis and primary tumors of the nervous system the corpora amylacea showed similar appearance with strong HSP-60 positivity in all investigated disorders at the predilection sites. In the inflammatory diseases, besides corpora amylacea, several cellular elements exhibited HSP-60 immunostaining too. In these cases, the widespread HSP-60 immunoreactivity associated with relative moderate corpora amylacea production as compared to other diseases. From this contradiction we concluded the corpora amylacea participate in the cellular stress reaction but stress protein synthesis certainly is not the primary event in corpora amylacea formation. In the development of the corpora amylacea the incipient process is most probably degenerative in nature, which later on is accompanied by stress protein synthesis and slow growing of these round structures designated for a protective role in the brain. However, the role of the stress protein synthesis in the corpora amylacea formation and growth was not unequivocally answered in this study. It is necessary to perform further comparative investigations of the stress protein representation and corpora amylacea formation in different diseases which may help in discovering useful pathogenetic data and the biological role of this degenerative structure.
C1 [Gati, Istvan] University of Pecs, Department of Neurology, Ret u. 2., H-7623 Pecs, Hungary.
[Leel-Ossy, Lorant] St. Borbala University Hospital, Department of Pathology, Neuropathological LaboratoryTatabanya, Hungary.
RP Gati, I (reprint author), University of Pecs, Department of Neurology, H-7623 Pecs, Hungary.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 140
EP 144
PG 5
ER
PT J
AU Leel-Ossy, L
AF Leel-Ossy, Lorant
TI New Data on the Ultrastructure of the Corpus Amylaceum (Polyglucosan Body)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Corpus amylaceum; ultrastructure; scanning EM; polyglucosan body
ID Corpus amylaceum; ultrastructure; scanning EM; polyglucosan body
AB During the semiquantitative evaluation of the occurrence of the corpus amylaceum (CA) in a large quantity of autopsy and biopsy material (1,407 cases), electromicroscopical (EM) and scanning EM examinations were carried out on 8 autopsied cases where CA was demonstrated. The EM examinations appeared to underline the astrocytic origin of the CA formation, which is initiated in the astrocytic fiber system by glycogen and other carbohydrate polymers. The biophysics of the development of the CA is indicative of the same mechanisms as for (mainly intracellular) inclusion bodies. The large amount of CA that develops at the predilection sites is a consequence of metabolic damage, a large quantity of cerebrospinal fluid and recurring disturbances in the barrier functions. The abundant CA may cause secondary blood-brain barrier disturbances. This working hypothesis demands further investigations and the continuation of research by modern immunocytochemical and ultrastructural methods recommended.
C1 [Leel-Ossy, Lorant] University Hospital of County Borsod-A.-Z., I. Department of Neurology and NeurosurgeryMiskolc, Hungary.
RP Leel-Ossy, L (reprint author), University Hospital of County Borsod-A.-Z., I. Department of Neurology and Neurosurgery, Miskolc, Hungary.
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Yoshimura T: Beitrage zu den klinisch - und histopathologischen Untersuchungen uber die Falle der Lafora-ahnlichen Einschlusskorperchen. Folia Psychiat Neurol Jpn 1977.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 145
EP 150
PG 6
ER
PT J
AU Szekely, E
Madaras, L
Kulka, J
Jaray, B
Nagy, L
AF Szekely, Eszter
Madaras, Lilla
Kulka, Janina
Jaray, Balazs
Nagy, Lajos
TI Leiomyosarcoma of the Female Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE breast tumors; leiomyosarcoma
ID breast tumors; leiomyosarcoma
AB Leiomyosarcomas of the breast are rare tumors. Less than 15 such cases have been reported in the literature so far. In this paper authors describe a case of leiomyosarcoma of a female breast presenting as a firm lobulated mass, mimicking a phylloid tumor radiographically. By fine needle aspiration biopsy, on the smears discohesive malignant looking cells were conclusive to a poorly differentiated invasive ductal carcinoma of the breast. The mastectomy specimen contained a lobulated mass, microscopically showing a partly epithelioid spindle cell tumor, immunoreactive for vimentin, desmin, smooth muscle actin antibodies, and negative for epithelial markers, hormone and growth factor receptors. Axillary lymph nodes were free of tumor. A primary leiomyosarcoma of the breast was diagnosed.
C1 [Szekely, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Madaras, Lilla] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Nagy, Lajos] Semmelweis University, 3rd Department of SurgeryBudapest, Hungary.
RP Szekely, E (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM szesz@korb2.sote.hu
CR Blanchard DK, Budde JM, Hatch GF: 3rd Tumors of the small intestine. World J Surg 24:421-429, 2000.
Burke AP, Virmani R: Sarcomas of the Great Vessels. A Clinicopathologic study. Cancer, 71:1761-1773, 1993.
Burke AP, Virmani R: Tumors of the heart and great vessels, AFIP, 1996.
Falconieri G, Della Libera D, Zanconati F, Bittesini L: Leiomyosarcoma of the Female Breast. Am J Surg Pathol 108:19- 25, 1997.
Glock Y, Laghzaoui A, Wang J: Fissured leiomyosarcoma of the descending thoracic aorta. A propos of a case and review of the literature. Arch Mal Coeur 90:1317-1320, 1997.
Palacios G: Leiomyosarcoma of the Female Breast. Am J Surg Pathol 109:650-651, 1998.
Majeski J, Crawford ES, Majeski EI: Primary aortic intimal sarcoma of the endothelial cell type with long term survival. J Vasc Surg 27:555-558, 1998.
Mentzel T, Calonje E, Fletcher CDM: Leiomyosarcoma with prominent osteoclast-like giant cells Am J Surg Pathol 18:258- 265, 1994.
Miracco C, Laurini L, Santopietro R: Intimal type primary sarcoma of the aorta. Report of a case with evidence of rhabdomyosarcomatous differentiation Virchows Arch 435:62-66, 1999.
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Pautier P, Genestie C, Rey A: Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma. Cancer 88:1425-1431, 2000.
Rochais JP, Icard P, Coffin O: Intimal sarcoma of the thoracic aorta: a case report. Eur J Vasc Endovasc Surg 18:181-182, 1999.
Roncaroli F, Eusebi V: Rhabdomyoblastic differentiation in a leiomyosarcoma of the retroperitoneum Hum Pathol 27:310- 313, 1996.
Shimoda H, Oka K, Otani S: Vascular leiomyosarcoma arising from the inferior vena cava diagnosed by intraluminal biopsy. Virchows Arch 433:97-100, 1998.
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Ugras S, Dilek ON, Karaayvaz M, et al: Primary Leiomyosarcoma of the Breast. Surg Today 27:1082-1085, 1997.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2001
VL 7
IS 2
BP 151
EP 153
PG 3
ER
PT J
AU Chatziantoniou, DV
AF Chatziantoniou, D Vassilios
TI Telomerase: Biological Function and Potential Role in Cancer Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE telomerase; telomeres; cancer; function; regulation; therapy
ID telomerase; telomeres; cancer; function; regulation; therapy
AB Telomeres are the specialized ends of eukaryotic chromosomes, thought to have many functions, most importantly serving as a clock signaling entry into cellular senescence. These structures are maintained by the reverse transcriptase telomerase, a peculiar enzyme in both structure, since it contains its own template RNA and function, since it is inactivated in most normal tissues but activated in the vast majority of malignant tumors. These features have made telomerase a subject of intense investigation, both to understand its cellular role and regulation and to exploit its activation in cancer to develop drugs or diagnostic methods based on telomerase. This work gathers all the information currently available in the biological and clinical fields of telomerase research.
C1 [Chatziantoniou, D Vassilios] Semmelweis UniversityBudapest, Hungary.
RP Chatziantoniou, DV (reprint author), Semmelweis University, Budapest, Hungary.
CR Blackburn EH: Structure and function of telomeres. Nature 350:569-572, 1991.
Kipling D., ed): The telomere. Oxford University Press, Oxford, 1995.
Griffith JK, Comeau L, Rosenfield S, et al: Mammalian telomeres end in a large duplex loop. Cell 97:503-514, 1999.
Jun-Ping Liu: Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J 13:2091-2104, 1999.
Blackburn EH: Telomerases. Annu Rev Biochemistry 61:113- 129, 1992.
Bhattacharyya A, Blackburn EH: A functional telomerase RNA swap in vivo reveals the importance of nontemplate RNA domains. Proc Natl Acad Sci USA 94:2823-2827, 1997.
Beattie TL, Zhou W, Robinson MO, et al: Reconstitution of human telomerase activity in vitro. Current Biology 8:177-180, 1998.
Kilian A, Bowtell DD, Abud HE, et al: Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types. Human Mol Genetic 6:2011-2019, 1997.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 161
EP 170
PG 10
ER
PT J
AU Esteva, JF
Hortobagyi, NG
Sahin, AA
Smith, LT
Chin, MD
Liang, ShY
Pusztai, L
Buzdar, UA
Bacus, SS
AF Esteva, J Francisco
Hortobagyi, N Gabriel
Sahin, A Aysegul
Smith, L Terry
Chin, Mon Dot
Liang, Shang-Ying
Pusztai, Lajos
Buzdar, U Aman
Bacus, S Sarah
TI Expression of erbB/HER Receptors, Heregulin and P38 in Primary Breast Cancer using Quantitative Immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumor markers; biological; proto-oncogene proteins; immunohistochemistry; ligands; breast neoplasm
ID Tumor markers; biological; proto-oncogene proteins; immunohistochemistry; ligands; breast neoplasm
AB The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand heregulin, and the two different signaling pathways p38 and mitogen-activated protein kinase (MAPK), as well as the status of HER-2 phosphorylation in tumor specimens from patients with primary breast cancer. The level of expression of these proteins was measured by quantitative immunohistochemistry combined with microscope-based image analysis in paraffin-embedded breast cancer tissue from 35 patients. The frequency of expression was: EGFR (51%), HER-2 (54%), P-HER-2 (48%), HER-3 (48%), HER-4 (57%), heregulin (48%), p38 (17%), MAPK (48%). There was evidence of associations among the coexpression of heregulin, EGFR, HER-2, and HER-3. Also, there was evidence of a positive association between P-MAPK and HER-4. HER-3 was expressed at high levels in patients younger than 50 years of age. There was a trend for expression of higher levels of HER-4 in tumors larger than 2 cm. The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status. The HER family of growth factor receptors appear to be regulated independently in invasive breast cancer. Assessing the expression of multiple tumor markers by quantitative immuno-histochemistry is feasible. Further research is needed to determine the prognostic and predictive roles of the various associations between HER receptors, their ligands and signal transduction molecules in patients with early-stage breast cancer.
C1 [Esteva, J Francisco] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 1515 Holcombe Boulevard, 77030-4095 Houston, Texas, USA.
[Hortobagyi, N Gabriel] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 1515 Holcombe Boulevard, 77030-4095 Houston, Texas, USA.
[Sahin, A Aysegul] The University of Texas M.D. Anderson Cancer Center, Department of PathologyHouston, Texas, USA.
[Smith, L Terry] The University of Texas M.D. Anderson Cancer Center, Department of BiostatisticsHouston, Texas, USA.
[Chin, Mon Dot] Quantitative Diagnostics LaboratoryElmhurst, Illinois, USA.
[Liang, Shang-Ying] The University of Texas M.D. Anderson Cancer Center, Department of BiostatisticsHouston, Texas, USA.
[Pusztai, Lajos] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 1515 Holcombe Boulevard, 77030-4095 Houston, Texas, USA.
[Buzdar, U Aman] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 1515 Holcombe Boulevard, 77030-4095 Houston, Texas, USA.
[Bacus, S Sarah] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 1515 Holcombe Boulevard, 77030-4095 Houston, Texas, USA.
RP Esteva, JF (reprint author), The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 77030-4095 Houston, USA.
CR Bacus SS, Gudkov AV, Esteva FJ, et al: Expression of erb-B receptors and their ligands in breast cancer: implications to biological behavior and therapeutic response. Breast Disease 11:63-75, 2000.
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Gasparini G, Gullick WJ, Bevilacqua P, et al: Human breast cancer: prognostic significance of the c-erb B-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features. J Clin Oncol 10:686-695, 1992.
Harris AL, Nicholson S, Sainsbury R, et al: Epidermal growth factor receptor and other oncogenes as prognostic markers. J Natl Cancer Inst 181-187, 1992.
Muss HB, Thor AD, Berry DA, et al: c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260-1266, 1994.
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Elledge RM, Green S, Ciocca D, et al: HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study. Clin Cancer Res 4:7- 12, 1998.
Lemoine NR, Barnes DM, Hollywood DP, et al: Expression of the ERBB3 gene product in breast cancer. Br J Cancer 66:1116- 1121, 1992.
Kumar NB, Cantor A, Allen K, et al: Android obesity at diagnosis and breast carcinoma survival – Evaluation of the effects of anthropometric variables at diagnosis, including body composition and body eat distribution and weight gain during life span, and survival from breast carcinoma. Cancer 88:2751- 2757, 2000.
Gullick WJ: The c-erbB3/HER3 receptor in human cancer. Cancer Surveys 27:339-349, 1996.
Kew TY, Bell JA, Pinder SE, et al: c-erbB-4 protein expression in human breast cancer. British Journal of Cancer 82:1163- 1170, 2000.
Xia Z, Dickens M, Raingeaud J, et al: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326- 1331, 1995.
Bacus SS, Plowman G, Yarden Y: Expression of erbB-2 receptor family and their ligands: implication to breast cancer biological behavior, Meeting abstract). Breast Cancer Res Treat 32:93-93, 1994.
Tang MTC, Weiss NS, Daling JR, et al: Case-control differences in the reliability of reporting a history of induced abortion. Amer J Epidemiol 151:1139-1143, 2000.
Drumea KC, Levine E, Bernstein J, et al: ATM heterozygosity and breast cancer: screening of 37 breast cancer patients for ATM mutations using a non-isotopic RNase cleavage-based. Breast Cancer Res Treat 61:79-85, 2000.
Wang TTY, Jeng JJ: Coordinated regulation of two TRAILR2/ KILLER/DR5 mRNA isoforms by DNA damaging agents, and 17 beta-estradiol in human breast cancer cells. Breast Cancer Research and Treatment 61:87-96, 2000.
Plowman GD, Culouscou JM, Whitney GS, et al: Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci USA 90:1746-1750, 1993.
Knowlden JM, Gee JM, Seery LT, et al: c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 17:1949-1957, 1998.
Lupu R, Lippman ME: William L. McGuire Memorial Symposium. The role of erbB2 signal transduction pathways in human breast cancer. Breast Cancer Res Treat 27:83-93, 1993.
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Bacus SS, Gudkov AV, Zelnick CR, et al: Neu differentiation factor, heregulin, induces expression of intercellular adhesion molecule 1: implications for mammary tumors. Cancer Res 53:5251-5261,1993.
Bacus SS, Gudkov AV, Esteva FJ, et al: Expression of erb-B Receptors and Their Ligands in Breast Cancer: Implications to Biological Behavior and Therapeutic Response, in Liu E, ed): The Breast, 2000.
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Bacus SS, Stancovski I, Huberman E, et al: Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res 52:2580- 2589, 1992.
Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401: 86-90, 1999.
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Xu FJ, Stack S, Boyer C, et al: Heregulin and agonistic antip185( c-erbB2, antibodies inhibit proliferation but increase invasiveness of breast cancer cells that overexpress p185(cerbB2): increased invasiveness may contribute to poor prognosis. Clin Cancer Res 3:1629-1634, 1997.
Harris LN, Yang L, Tang C, et al: Induction of sensitivity to doxorubicin and etoposide by transfection of MCF-7 breast cancer cells with heregulin beta-2. Clin Cancer Res 4:1005- 1012, 1998.
Bacus SS, Gudkov AV, Lowe M, et al. Taxol-induced cytotoxicity: apoptotic signaling via MAP kinase pathways. Oncogene. 20:147-155, 2001.
Komurasaki T, Toyoda H, Uchida D, et al: Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene 15:2841-2848, 1997.
Tzahar E, Pinkas-Kramarski R, Moyer JD, et al: Bivalence of EGF-like ligands drives the ErbB signaling network. EMBO J 16:4938-4950, 1997.
Pinkas-Kramarski R, Lenferink AE, Bacus SS, et al: The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin. Oncogene 16:1249- 1258, 1998.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 171
EP 177
PG 7
ER
PT J
AU Pal, J
Somogyi, Cs
Szmolenszky,
Szekeres, Gy
Sipos, J
Hegedus, G
Martzinovits, I
Molnar, J
Nemeth, P
AF Pal, Jozsef
Somogyi, Csilla
Szmolenszky, Agnes
Szekeres, Gyorgy
Sipos, Jozsef
Hegedus, Geza
Martzinovits, Ilona
Molnar, Janos
Nemeth, Peter
TI Immunohistochemical Assessment and Prognostic Value of Hepatitis B Virus X Protein in Chronic Hepatitis and Primary Hepatocellular Carcinomas using anti-HBxAgMonoclonal Antibody
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE primary hepatocellular carcinoma; hepatitis-B X protein; chronic B virus hepatitis; monoclonal anti-HBx antibody; immunohistochemistry
ID primary hepatocellular carcinoma; hepatitis-B X protein; chronic B virus hepatitis; monoclonal anti-HBx antibody; immunohistochemistry
AB Hepatitis B virus (HBV) is the most meaningful risk factor in chronic hepatitis, cirrhosis and primary hepatocellular carcinoma (PHC). The hepatitis B virus X protein (HBxAg) is a multifunctional protein with many important functions in hepatocellular carcinogenesis. A monoclonal anti-HBxAg antibody was developed in our laboratory and characterized by different methods. Using this antibody HBxAg was detected in formaldehyde fixed paraffin embedded tissue sections of 72 liver biopsies from patients with acute hepatitis, chronic hepatitis, cirrhosis and primary hepatocellular carcinoma. The co-expression of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and HBxAg was compared. The histological and cytological localization of the detected HBxAg showed a characteristic distribution in different stages of HBV infection. Strong and diffuse nuclear reaction was detected in PHC cases in contrast to the focal, cytoplasmic and nuclear labeling in the acute and chronic B hepatitis cases. Our antibody seems to be a suitable prognostic marker for routine pathohistological diagnosis and for comparative pathological and epidemiological research on the development of PHC.
C1 [Pal, Jozsef] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Somogyi, Csilla] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Szmolenszky, Agnes] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Szekeres, Gyorgy] Hisztopatologia KFTPecs, Hungary.
[Sipos, Jozsef] County Hospital of Zala, Department of PathologyZalaegerszeg, Hungary.
[Hegedus, Geza] County Hospital of Baranya, Department of PathologyPecs, Hungary.
[Martzinovits, Ilona] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Institute of Clinical MicrobiologySzeged, Hungary.
[Molnar, Janos] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Institute of Clinical MicrobiologySzeged, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
RP Nemeth, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM peter.nemeth@aok.pte.hu
CR Andrisani OM, Barnabas S: The transcriptional function of the hepatitits B virus X protein and its role in hepatocarcinogenesis., Review, Internat J Oncol 15:373-379, 1999.
Balogh P, Szekeres Gy, Nemeth P: Hapten-mediated identification of cell membrane antigens using an anti-FITC monoclonal antibody. J Immunol Method 169:35-40, 1994.
Brechot C: Molecular Mechanisms of Hepatitis B and C Viruses Related to Liver Carcinogenesis. Hepato-Gastroenterology 45:1189-1196, 1998.
Diamantis ID, McGandy CE, Chen TJ, et al: Hepatitis B X-gene expression in hepatocellular carcinoma. J Hepatol 15:400-403, 1992.
Doria M, Klein N, Lucito R, et al: The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of Transcription factor. EMBO J 14:4747- 4757, 1995.
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Hess J, Stemler M, Will H, et al: Frequent detection of antibodies to hepatitis B x-protein in acute, chronic and resolved infections. Medical Microbiol Immunol 177:195-205, 1988.
Katayama K, Hayashi N, Sasaki Y, et al: Detection of Hepatitis B Virus X Gene protein and Antibody in Type B Chronic Liver DiseaseGastroenterology 97:990-998, 1989.
Kay A, Dinechin SD,Vitvitski-Trepo L, et al: Recognition of the N-Terminal, C-Terminal, and Interior Portions of HBx by Sera From Patients With Hepatitis B. J Med Virol 33:228-235, 1991.
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Kumar V, Jayasuryan N, Reddi H, et al: A Monoclonal Antibody Against the X Protein of Hepatitis B Virus: Fine Mapping of its Epitope and Application in a Quantitative ELISA of the X Protein in Sera of Hepatitis B Patients. Hybridoma 17:2, 1998.
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Zhu M, London WT, Duan L-X, et al: The value of hepatitis B x antigen as a prognostic marker in the development of hepatocellular carcinoma. Int J Cancer 55:571-576, 1993.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 178
EP 184
PG 7
ER
PT J
AU Altinoz, AM
Ozar, E
Taskin, M
Bozcali, E
Bilir, A
Altug, T
Aydiner, A
Sav, A
AF Altinoz, A Meric
Ozar, Engin
Taskin, Murat
Bozcali, Evin
Bilir, Ayhan
Altug, Tuncay
Aydiner, Adnan
Sav, Aydin
TI Vascularization Pattern of C6 Glioma is Modified with Medroxyprogesterone Acetate and Ibuprofen in Wistar Rat Brain
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE medroxyprogesterone; ibaprofen; glioma; angiogenesis
ID medroxyprogesterone; ibaprofen; glioma; angiogenesis
AB Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.
C1 [Altinoz, A Meric] Faculty of Medicine, Istanbul University, Department of Histology and EmbryologyBakirkoy, Turkey.
[Ozar, Engin] Bakirkoy Mental Diseases Hospital, 1 st Neurosurgery ClinicBakirkoy, Turkey.
[Taskin, Murat] Bakirkoy Mental Diseases Hospital, 1 st Neurosurgery ClinicBakirkoy, Turkey.
[Bozcali, Evin] Faculty of Medicine, Istanbul University, Department of Histology and EmbryologyBakirkoy, Turkey.
[Bilir, Ayhan] Faculty of Medicine, Istanbul University, Department of Histology and EmbryologyBakirkoy, Turkey.
[Altug, Tuncay] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Aydiner, Adnan] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Sav, Aydin] Marmara University, Institute of Neuroscience, Talia Bali Aykan Neuropathology Laboratory, General Sukru Kanatli Sok. No: 36/8Bakirkoy, Turkey.
RP Sav, A (reprint author), Marmara University, Institute of Neuroscience, Talia Bali Aykan Neuropathology Laboratory, Bakirkoy, Turkey.
EM maltinoz@hotmail.com
CR Blei F, Wilson EL, Mignatti P, et al: Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis. J Cell Physiology 155:568-578, 1993.
Bourdon MA, Wikstrand CJ, Furthmayr H, et al: Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res 43:2796-2805, 1983.
Chow G, Woronick A, Kinkade P, et al: Pharmacological modulation of plasminogen activator secretion by P388D1 cell line. Agents Actions 21:387-389, 1987.
Farrell CL, Megyesi JM, Maestro FRD: Effect of ibuprofen on tumor growth in the C6 spheroid implantation glioma model. J Neurosurg 68:925-930, 1998.
Fujimoto J, Hosoda S, Fujita H, et al: Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer. Invasion Metastasis 9:209-215, 1989.
Haddad SF, Moore SA, Schelper RL, et al: Smooth muscle can comprise the sarcomatous component of gliosarcomas. J Neuropathol Exp Neurol 51:493-498, 1992.
Haddad SF, Moore SA, Schelper RL, et al: Vascular smooth muscle hyperplasia underlies the formation of glomeruloid vascular structures of glioblastoma multiforme. J Neuropathol Exp Neurol 51:493-498, 1992.
Hyder SM, Murthy L, Stancel GM, et al: Progestin regulation of vascular endothelial growth factor in human breast cancer cells. Cancer Res 58:392-395, 1998.
Iwamoto T, Tamaki K, Nakayama M, et al: Effect of endothelin 1 on fibrinolysis and plasminogen activator inhibitor 1 synthesis in rat mesangial cells. Nephron 73:273-297, 1996.
Jikihara H., Terada N., Yamamoto R., et al: Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer. Am J Obstet Gynecol 167:207-211, 1992.
Khalid H, Shibata S, Kishikawa M, et al: Immunohistochemical analysis progesterone receptor and Ki-67 labelling index in astrocytic tumors. Cancer 80:2133–2140, 1997.
Kono S, Rao JS, Bruner JM, et al: Immunohistochemical localization of plasminogen activator type 1 in human brain tumors. J Neuropathol Exp Neurol 53:256-262, 1994.
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Rao BR: Pregnancy associated highly vascularized tumors negatively correlate with the levels of antiangiogenic 17 alphahydroxy- progesterone. Anticancer Res 17:1019-1021, 1999.
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Selby DM, Woodard CA, Henry ML, et al: Are endothelial cell patterns indicative of grade. In vivo 11:371-375, 1997.
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Wadgymar A, Halloran PF: Crossreactions between an I-A allospecificity and the cytoskeleton of glomerular epithelium and of vascular smooth muscle. Transplantation 43:93-98, 1987.
Yoshida Y, Kumanishi T, Abe S: Glomeruloid blood vessels in ethylnitrosourea-induced rat gliomas. Histological and immunohistochemical studies. Acta Neuropathol 79:240-247, 1989.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 185
EP 189
PG 5
ER
PT J
AU Aziz, AS
Pervez, Sh
Khan, Sh
Kayani, N
Azam, IS
Rahbar, HM
AF Aziz, Abdus Syed
Pervez, Shahid
Khan, Shaista
Kayani, Naila
Azam, Igbal Syed
Rahbar, Hussain Mohammed
TI Significance of Immunohistochemical c-ErbB-2 Product Localisation Pattern for Prognosis in Human Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-ErbB-2; breast cancer; prognosis; drug resistance; nodal metastases
ID c-ErbB-2; breast cancer; prognosis; drug resistance; nodal metastases
AB Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified, including c-ErbB-2. In this study, expression of c-ErbB-2 in breast carcinoma was correlated with axillary lymph node metastases and disease outcome. The expression of c-ErbB-2 oncoprotein was analysed in 315 tumor specimens of infiltrating ductal carcinoma of breast. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. These patients also had axillary lymph nodes sampling. The expression of c-ErbB-2 oncoprotein was analysed immunohistochemically. Over expression of c-ErbB-2 were observed in 39.36% tumors. Axillary lymph node metastasis had significant correlation with intensified positivity of c-ErbB-2. C-ErbB-2 positive patients did show resistance to chemotherapy when compared for recurrence and distant metastases following surgery (p< 0.05). At a median follow-up of 48 months in c-ErbB-2 positive patients, the overall survival was 3.0 years and disease free survival was 2.5 years. c-ErbB-2 negative tumor patients showed a far better survival. In this group the overall survival was 4.44 years and the disease free survival was 3.78 years. These findings reinforce the view that c-ErbB-2 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.
C1 [Aziz, Abdus Syed] The Aga Khan University, Department of Pathology and Microbiology, Stadium RoadKarachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and Microbiology, Stadium RoadKarachi, Pakistan.
[Khan, Shaista] The Aga Khan University, Department of SurgeryKarachi, Pakistan.
[Kayani, Naila] The Aga Khan University, Department of Pathology and Microbiology, Stadium RoadKarachi, Pakistan.
[Azam, Igbal Syed] The Aga Khan University, Department of CHSKarachi, Pakistan.
[Rahbar, Hussain Mohammed] The Aga Khan University, Department of CHSKarachi, Pakistan.
RP Pervez, Sh (reprint author), The Aga Khan University, Department of Pathology and Microbiology, Karachi, Pakistan.
EM shahid.pervez@aku.edu
CR Guido S, Georg F, Joachim T: Fluorescence in Situ Hybridization for detecting C-ErbB-2 amplification in breast tumor fine needle aspiration biopsies. Acta Cytologica 40:164-173, 1996.
Muss HB, Thor AD, Berry DA: Cerb-B-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260-1266, 1994.
William C: More than one way to look for HER-2. Cap Today 13:31-54, 1999.
Perren TJ: C-ErbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer 63:328-332, 1991.
van de Vijver MJ, Peterse JL, Mooi WJ: Neu-protein over expression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 319:1239-1245, 1988.
Aryandono-T, Harijadi, Ghozali-A: Correlation of clinical, pathological status, hormone receptor and C-ErbB-2 oncoprotein in breast cancer patients. Gan-To-Kagaku-Ryoho Suppl 2:600-606, 2000.
Looi-LM, Cheah-PL: C-ErbB-2 oncoprotein amplification in infiltrating ductal carcinoma of breast relates to high histological grade and loss of oestrogen receptor protein. Malays J Pathol. 20:19-23, 1998.
Wright C, Angus B, Nicholson S:Expression of c-ErbB-2- oncoprotein: a prognostic indicator in human breast cancer. Cancer Res 49:2087-2090, 1989.
Walker RA, Gullick WJ, Varley JM: An evaluation of immunoreactivity for C-ErbB-2 protein as a marker of poor short-term prognosis in breast cancer. Br J Cancer 60:426-429, 1989.
Barnes DM, Lammie GA, Millis RR: An immunohistochemical evaluation of C-ErbB-2 gene expression in human breast carcinoma. Br J Cancer 58:448-452, 1988.
Gusterson BA, Gelber RD, Goldhirsch A: Prognostic significance of C-ErbB-2 expression in breast cancer. J Clin Oncol 10:1046-1049, 1992.
Tandon AK, Clark GM, Chamness GC: HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Onco 1989; 17:1120-1128, 1989.
Tsuda H, Hirohashi S, Shimasto Y: Correlation between longterm survival in breast cancer patients and amplification of two putative oncogene-coamplification units, hst-1 / int-2 and CErbB- 2 / ear-1. Cancer Res 49:3104-3110, 1989.
Borg A, Tandon AK, Sigurdsson H: HER-2/ neu amplification predicts poor survival in node-negative breast cancer. Cancer Res 50:4332-4337, 1990.
Slamon DJ, Clark GM, Wong SG: Human breast cancer: Correlation of relapse and survival with amplification of HER-2/neu oncogene. Science 235:177-183, 1987.
Wright C, Angus B, Nicholson S:Expression of c-ErbB-2- oncoprotein: a prognostic indicator in human breast cancer. Cancer Res 49:2087-2090, 1989.
Gullick WL, Wright C, Barnes D: C-ErbB-2 protein overexpression in breast carcinoma is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer 63:434- 438, 1991.
Cobleigh MA, Vogel CL, Tripathy D:Efficacy and safety of herceptin as a single agent in 222 women with HER-2 over expression who relapsed following chemotherapy for metastatic breast cancer. ASCO, Los Angeles California 1998; Abstract 376.
Slamon D, Leyland-Jones B, Shak S: Addition of herceptin to first line chemotherapy for HER-2 over expression metastatic breast cancer markedly increases anticancer activity; A randomised multinational controlled phase III trial. ASCO, Los Angeles California 1998; Abstract 377.
Jakic-Razumovic-J, Petrovecki-M, Uzarevic-B: Mutual predictive value of c-ErbB-2 over expression and various prognostic factors in ductal invasive breast carcinoma. Tumori 86:30-36, 2000.
King CR, Kraus MH, Aaronson SA: Amplification of a v-erbB related gene in human mammary carcinoma. Science 229:974- 976, 1985.
Berger MS, Locher GW, Saurer S: Correlation of C-ErbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48:1238- 1243, 1985.
Slamon DJ, Godolphin W, Lones LA: Studies of HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707-712, 1989.
Ali IU, Campbell G, Lidereau R: Amplification of C-ErbB-2 and aggressive human breast tumors. Science 235:1795-1798, 1988.
Bernard T, Jacques B: Prognostic significance of HER-2 /neu oncoprotein expression in node-positive breast cancer. Cancer 73:2359-2365, 1994.
Sharma BK, Ray A, Kaur S: Immunohistochemical co-expression of c-ErbB-2/Neu oncoprotein, altered tumor suppressor, p53, protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast. Indian J Exp Biol 37: 223-227, 1999.
Shimizu C, Fukutomi T, Tsuda H: c-ErbB-2 protein over expression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol 73:17-20, 2000.
Baselga J, Tripathy D, Mendelsohn J: Phase II study of weekly intravenous trastuzumab, Herceptin, in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol 26, Suppl 12): 78-83, 1992.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 190
EP 196
PG 7
ER
PT J
AU Popovic, M
Hrcenjak, MT
Babic, T
Kos, J
Grdica, M
AF Popovic, Maja
Hrcenjak, Mihaela Terezija
Babic, Tomislav
Kos, Josip
Grdica, Mira
TI Effect of Earthworm (G-90) Extract on Formation and Lysis of Clots Originated from Venous Blood of Dogs with Cardiopathies and with Malignant Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE homeostasis; cardiopathy; malignant tumors; earthworm extract (G-90)
ID homeostasis; cardiopathy; malignant tumors; earthworm extract (G-90)
AB The stability of homeostasis is important to keep a balance between coagulation and fibrinolysis. A disorder of homeostasis leads to different physiological changes and causes different diseases such as cardiopathies and malignant tumors. Cardiopathies is characterized by a hypercoagulation. In the malignant tumors, besides the hypercoagulation due to plasminogen activators (PA) formed inside the tumor, a disorder of homeostasis leads also to acceleration of the fibrinolysis. The variety of internal and external factors in both cases determine the deviation of time for the clots formation, as well as the lyses of blood and fibrin clots. In this study the venous blood as well as the blood and the fibrin clots, derived from healthy dogs, the dogs with cardiopathies and with malignant tumors, were examined for the time of coagulation and fibrinolysis by adding different substances. In these experiments we used a glycolipoprotein extract from earthworm tissue homogenate (G-90) and the proteolytic enzymes P I and P II, isolated from G-90. The efficacy of the tested substances was comparable with the clinically administered anticoagulants. The most significant differences in clotting time among the three tested groups of dogs were obtained by application of the original G-90. The results suggest a possibility that G-90, along with the fibrinolytic enzymes and other biologically active factors, also contains a factor that decelerates the formation of clot in a specific medium, such as the blood from the dogs with malignant tumors.
C1 [Popovic, Maja] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55, 10000 Zagreb, Croatia.
[Hrcenjak, Mihaela Terezija] Faculty of Veterinary Medicine, Department of Biology, Heinzelova 55, 10000 Zagreb, Croatia.
[Babic, Tomislav] Faculty of Veterinary Medicine, Ruder Bockovic Institute,, Department of SurgeryZagreb, Croatia.
[Kos, Josip] Faculty of Veterinary Medicine, Ruder Bockovic Institute,, Department of SurgeryZagreb, Croatia.
[Grdica, Mira] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
RP Popovic, M (reprint author), Faculty of Veterinary Medicine, Department of Biology, 10000 Zagreb, Croatia.
EM mpopovic@vef.hr
CR Brommer EJP, Emeis JJ, Verheijen JH, et al: Progress in Clinical Fibrinolysis. In: 7 Recent Advances in Blood Coagulation., Eds. Poller L and Ludlam CA), Churchill Livingstone, 1997, pp 161-182.
Gandolfo GM, Conti L, Vercillo M: Fibrinolysis Components as Prognostic Markers in Breast Cancer and Colorectal Carcinoma. Anticancer Res 16:2155-2160, 1992.
Glassman A: Hemostatic abnormalities associated with cancer and its therapy. Ann Clini Labo Sci 27:391-395, 1997.
Dickneite G, Nicolay U, Friesen HJ, et al: Development of an anti-bleeding agent for recombinant hirudin induced skin bleeding in the pig. Thrombo Haemost 80:192-198, 1998.
Du Z, Li X, Qian J, et al: Effect of earthworm fibrinolytic enzyme given orally on the activity of plasmin and on platelet aggregation in beagles dogs. Acta Acade Medi Shang 25:229- 231, 1998.
Hrenjak T, Hrenjak M, Kauba V, et al: A new source of biologically active compounds-earthworm tissue, Eisenia foetida, Lumbricus rubelus). Comp Biochem Physiol 102A:441-447, 1992.
Hrenjak M, KobrehelÐ, Levanat S: Mitogenicity of the earthworm’s, Eisenia foetida, insulin-like proteins. Comp Biochem Physiol 104B:723-729,1993.
Hrenjak T, PopoviaeM, BoiaeT, et al: Fibrinolytic and anticoagulative activities from the earthworm Eisenia foetida. Comp Biochem Physiol 119B:825-832, 1998.
Hrenjak T, PopoviaeM, Tika-Rudman LJ: Fibrinolytic activity of earthworms extract, G-90, on lysis of fibrin clots originated from the venous blood of patients with malignant tumors. Pat Oncol Res 3:206-211, 1998.
Oberhoff C, Szymeczek J, Hoffmann O, et al: Adjuvant antiestrogen treatment with tamoxifen in postmenopausal women with breast cancer: A longitudinal study of blood coagulation and fibrinolysis. Breast Canc Res Treat 50:73-81, 1998.
Okita Y, Takamoto S, Ando M, et al: Coagulation and fibrinolysis system in aortic surgery under deep hypothermic ciculatory arrest with aprotinin. The importance of adequate heparinization. Circulation 96:376-381, 1997.
PopoviaeM, Grdia M, VukoviaeS, et al: Adhesins of immunoglobulin- like superfamily from earthworm Eisenia foetida. Gen Pharmacol 30: 795-800, 1997.
Sagripanti A, Capri A, Zacharski LR: The Pathophysiology of the haemostatic system in cancer patients: Insights gained from studies using plasmatic markers of haemostatic system activation. In: Cancer and Blood Coagulation: basic and clinical aspect., Eds. Sagripanti A, Carpi A and Zacharski LR), Ets Editrice, 1990, pp 69-92.
Van Zutphen LFM, Baumans V, Beynen AC: Principles of Laboratory animal science., Eds. Van Zutphen LFM, Baumans V and Beynen A C), Elsevier Science Publishers, 1993.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 197
EP 202
PG 6
ER
PT J
AU Arora, S
Mathew, R
Mathur, M
Chattopadhayay, KT
Ralhan, R
AF Arora, Sonia
Mathew, Robin
Mathur, Meera
Chattopadhayay, Kant Tushar
Ralhan, Ranju
TI Alterations in MDM2 Expression in Esophageal Squamous Cell Carcinoma: Relationship with p53 Status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MDM2; p53; mutation; oncogene; esophageal squamous cell carcinoma
ID MDM2; p53; mutation; oncogene; esophageal squamous cell carcinoma
AB In view of the significance of MDM2 as a regulator as well as critical target of wild type p53, this study was undertaken to determine the alteration in MDM2 expression in esophageal squamons cell carcinoma (ESCC) and its relationship to clinicopathological parameters as well as p53gene and protein status. Immunohistochemical analysis of MDM2 and p53 proteins on paraffin embedded sections from 64 surgically resected ESCCs and matched histologically normal tissues showed overexpression of MDM2 protein in 23/64 (36%) ESCCs, while the histopathologically normal esophageal tissues did not show detectable level of MDM2 immunoreactivity. Interestingly, MDM2 – /p53 + phenotype was observed in 37/64 (58%) cases. None of the cases with p53 mis-sense mutations (12/30, 40%) showed detectable level of MDM2 protein. Missense p53 mutations were significantly associated with discordant p53 + /MDM2 – immunophenotype (p= 0.004). The most intriguing feature of the study was accumulation of MDM2 in the absence of detectable p53 in 11% of and overexpression of MDM2 and p53 in 25% of ESCCs, suggesting a p53-independent role for MDM2 in a subset of tumors. These results underscore the involvement of MDM2 in p53-dependent and -independent pathways in the pathogenesis of esophageal cancer in the Indian population.
C1 [Arora, Sonia] All India Institute of Medical Sciences, Department of Biochemistry, 110029 Ansari Nagar, New Delhi, India.
[Mathew, Robin] All India Institute of Medical Sciences, Department of Biochemistry, 110029 Ansari Nagar, New Delhi, India.
[Mathur, Meera] All India Institute of Medical Sciences, Department of PathologyAnsari Nagar, New Delhi, India.
[Chattopadhayay, Kant Tushar] All India Institute of Medical Sciences, Department of SurgeryAnsari Nagar, New Delhi, India.
[Ralhan, Ranju] All India Institute of Medical Sciences, Department of Biochemistry, 110029 Ansari Nagar, New Delhi, India.
RP Ralhan, R (reprint author), All India Institute of Medical Sciences, Department of Biochemistry, 110029 Ansari Nagar, New Delhi, India.
EM ralhanr@hotmail.com
CR Barak Y, Juven T, Hafner R, et al: MDM2 expression is induced by wild type p53 activity. EMBO J 12:461-468, 1993.
Cahilly Snyder L, Yang-Feng T, Francke U, et al: Molecular analysis and Chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Molec Genet 13:235-244, 1987.
Cordon-Cardo C, Latres E, Drobnjak M, et al: Molecular abnormalities of mdm-2 and p53 genes in adult soft tissue sarcomas. Canc Res 54:794-799, 1994.
El-Deiry WS, Harper JW, O’Connor PM, et al: p21 is induced in p53-mediated G1 arrest and apoptosis. Canc Res 54:1169, 1994.
Fakhar-Zadeh SS, Trusko SP, George DC: Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 10:1565-1569, 1991.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 203
EP 208
PG 6
ER
PT J
AU Karaburun Paker, S
Kilicarslan, B
Ciftcioglu, MA
Oztekin, S
Sargin, CF
Erdogru, T
Baykara, M
AF Karaburun Paker, Semra
Kilicarslan, Bahar
Ciftcioglu, M Akif
Oztekin, Sevim
Sargin, C Figen
Erdogru, Tibet
Baykara, Mehmet
TI Relationship Between Apoptosis Regulator Proteins (bcl-2 and p53) and Gleason Score in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; bcl-2; prostate cancer; apoptosis
ID p53; bcl-2; prostate cancer; apoptosis
AB Cellular proliferation programmed cell death (apoptosis) are associated with tumor growth in general, and prostate cancer growth in particular. The aim of this study was to examine the expression of the apoptosis regulating genes bcl-2 and p53 and Gleason score in core needle biopsy specimens of prostate cancer using immunohistochemistry. We studied bcl-2 and p53 expression in 12 cases of low grade (Gleason score 2-5), 12 cases of intermediate grade (Gleason score 6-7) and 8 cases of high grade (Gleason score 8-10) prostate cancer. Overexpression of bcl-2 was noted in 3 of 32 patients (9.32%). One of them was high grade; others were intermediate grades. Expression of p53 was observed in 3 of low grades; others were high grade. The statistical analysis of present data suggest that there is no significant relation between p53 and bcl-2 expression and Gleason score in prostate cancer.
C1 [Karaburun Paker, Semra] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Kilicarslan, Bahar] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Ciftcioglu, M Akif] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Oztekin, Sevim] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Sargin, C Figen] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Erdogru, Tibet] Akdeniz University, Faculty of Medicine, Department of UrologyAntalya, Turkey.
[Baykara, Mehmet] Akdeniz University, Faculty of Medicine, Department of UrologyAntalya, Turkey.
RP Kilicarslan, B (reprint author), Akdeniz University, Faculty of Medicine, Department of Pathology, Antalya, Turkey.
EM bkilicarslan@hotmail.com
CR Bauer JJ, Sesterhenn IA, Mostofi FK, et al: Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol 156:1511-1516, 1996.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 209
EP 212
PG 4
ER
PT J
AU Resmiye, K
Pesterel, EH
Erdogan, G
Gulkesen, HK
Karavel, S
AF Resmiye, Kaya
Pesterel, Elif Hadice
Erdogan, Gulgun
Gulkesen, Hakan Kemal
Karavel, Seyda
TI Proliferating Activity in Differential Diagnosis of Benign Phyllodes Tumor and Cellular Fibroadenomas: Is It Helpful?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Phyllodes tumor; fibroadenoma; proliferating activity
ID Phyllodes tumor; fibroadenoma; proliferating activity
AB Benign phyllodes tumors and fibroadenomas are two types of fibroepithelial tumors of breast that are usually difficult to differentiate. The purpose of this study is to evalute the proliferative activity of these tumors and to find out if it helps in differential diagnosis. Thirty-one benign phyllodes tumors and twelve cellular fibroadenomas were retrieved from the archives of Pathology Department of Akdeniz University, School of Medicine. Proliferating activity of epithelial and stromal cells were evaluated by using labeling index (LI) of proliferating cell nuclear antigen (PCNA) and Ki-67 antigen by immunohistochemistry. The results were compared with other clinicopathologic findings. There was not any significant difference between the proliferating activity of phyllodes tumor and cellular fibroadenomas. Mean LI of PCNA was 28.01 (±22.85) in stromal cells and 56.57 (±30.98) in epithelial cells of phyllodes tumor where it was 28.92 (±24.02) and 62.53 (±32.56) in fibroadenomas. Ki-67 indices were 0.05 (±0.19) in stromal cells, 2.65 (±12.53) in epithelial cells of phyllodes tumors and 0.0 (±0) in stromal cells, 0.43 (±0.63) in epithelial cells of fibroadenomas. There was no correlation between the diameter of tumors and proliferating activity in both groups. Proliferating activity, determined by immunohistochemistry with PCNA and Ki-67 antibodies did not reveal significant difference between phyllodes tumor and fibroadenoma.
C1 [Resmiye, Kaya] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi Tip Fakultesi, Patoloji Anabilim Dali, ArapsuyuAntalya, Turkey.
[Pesterel, Elif Hadice] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi Tip Fakultesi, Patoloji Anabilim Dali, ArapsuyuAntalya, Turkey.
[Erdogan, Gulgun] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi Tip Fakultesi, Patoloji Anabilim Dali, ArapsuyuAntalya, Turkey.
[Gulkesen, Hakan Kemal] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi Tip Fakultesi, Patoloji Anabilim Dali, ArapsuyuAntalya, Turkey.
[Karavel, Seyda] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi Tip Fakultesi, Patoloji Anabilim Dali, ArapsuyuAntalya, Turkey.
RP Pesterel, EH (reprint author), Akdeniz University, Faculty of Medicine, Department of Pathology, Antalya, Turkey.
EM epestereli@superonline.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 213
EP 216
PG 4
ER
PT J
AU Timar, J
Csuka, O
Orosz, Zs
Jeney, A
Kopper, L
AF Timar, Jozsef
Csuka, Orsolya
Orosz, Zsolt
Jeney, Andras
Kopper, Laszlo
TI Molecular Pathology of Tumor Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE metastatic cascade; extracellular matrix interaction; metastatic phenotype; lung cancer; breast cancer; colon cancer; prostate cancer; malignant melanoma
ID metastatic cascade; extracellular matrix interaction; metastatic phenotype; lung cancer; breast cancer; colon cancer; prostate cancer; malignant melanoma
AB Millenium reviews of oncology agreed that the last century produced major developments mainly in the management of the primary tumor, but despite all of these results, cancer still remains among the leading causes of death due to the failure of clinical management of disseminated disease. This failure is primarily due to the lack of detailed information on the molecular mechanisms of tumor metastasis. Therefore, one of the hottest fields in experimental oncology is metastasis research, which provides more and more information about the molecular mechanisms. However, this information is fragmented and is not yet exploited in clinical practice. A new field of diagnostic pathology recently emerged, which translates basic research data to diagnostic practice to provide clinically relevant information on the biological potential (in this case metastatic potential) of the malignant tumors. Since tumor cell-extracellular matrix interactions are key features of tumor dissemination, expression of genes responsible for them can define the metastatic potential of malignant tumors. This review summarizes our recent knowledge on the metastatic geno- and phenotype of major human solid tumors: lung, colon, breast, prostate cancers and malignant melanoma.
C1 [Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H-1122 Budapest, Hungary.
[Csuka, Orsolya] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H-1122 Budapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Department of Tumor Progression, Rath Gy. U. 7-9., H-1122 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2001
VL 7
IS 3
BP 217
EP 230
PG 14
ER
PT J
AU Polgar, Cs
Fodor, J
Major, T
Orosz, Zs
Nemeth, Gy
AF Polgar, Csaba
Fodor, Janos
Major, Tibor
Orosz, Zsolt
Nemeth, Gyorgy
TI The Role of Boost Irradiation in the Conservative Treatment of Stage I-II Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE breast cancer; radiotherapy; boost; brachytherapy; electron; local control
ID breast cancer; radiotherapy; boost; brachytherapy; electron; local control
AB In this article, we review the current status, indication, technical aspects, controversies, and future prospects of boost irradiation after breast conserving surgery (BCS). BCS and radiotherapy (RT) of the conserved breast became widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of RT after breast conservation is to treat the whole breast up to a total dose of 45 to 50 Gy. However, there is no consensus among radiation oncologists about the necessity of boost dose to the tumor bed. Generally accepted criteria for identification of high risk subgroups, in which boost is recommended, have not been established yet. Further controversy exists regarding the optimal boost technique (electron vs. brachytherapy), and their impact on local tumor control and cosmesis. Based on the results of numerous retrospective and recently published prospective trials, the European brachytherapy society (GEC-ESTRO), as well as the American Brachytherapy Society has issued their guidelines in these topics. These guidelines will help clinicians in their medical decisions. Some aspects of boost irradiation still remain somewhat controversial. The final results of prospective boost trials with longer follow-up, involving analyses based on pathologically defined subgroups, will clarify these controversies. Preliminary results with recently developed boost techniques (intraoperative RT, CT-image based 3D conformal brachytherapy, and 3D virtual brachytherapy) are promising. However, more experience and longer follow-up are required to define whether these methods might improve local tumor control for breast cancer patients treated with conservative surgery and RT.
C1 [Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Fodor, Janos] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Major, Tibor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Department of Diagnostic Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Nemeth, Gyorgy] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Polgar, Cs (reprint author), National Institute of Oncology, Center of Radiotherapy, H-1122 Budapest, Hungary.
EM polgar@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 241
EP 250
PG 10
ER
PT J
AU Qian, X
Rothman, LV
Nicosia, FR
Tuszynski, PG
AF Qian, Xiaohua
Rothman, L Vicki
Nicosia, F Roberto
Tuszynski, P George
TI Expression of Thrombospondin-1 in Human Pancreatic Adenocarcinomas: Role in Matrix Metalloproteinase-9 Production
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE extracellular matrix; thrombospondin-1; matrix metalloproteinase; pancreatic cancer; tumor invasion; tissue inhibitor of metalloproteinase
ID extracellular matrix; thrombospondin-1; matrix metalloproteinase; pancreatic cancer; tumor invasion; tissue inhibitor of metalloproteinase
AB Human pancreatic adenocarcinoma, an aggressive malignant disease, shows a strong desmoplastic reaction characterized by a remarkable proliferation of interstitial connective tissues. Thrombospondin-1 (TSP-1), a 450 kDa platelet and matrix glycoprotein, has been implicated in tumor invasion, angiogenesis and metastasis. TSP-1 and MMP-9 expression in pancreatic adenocarcinoma and control pancreas tissues was measured by immunohistochemistry. TSP-1 expression in pancreatic carcinoma cell lines, fibroblasts, and endothelial cells was measured by a competitive TSP-1 enzyme linked immunosorbent assay (ELISA). The effect of TSP-1 on MMP-9 production in pancreatic carcinoma cell lines was measured by zymography and Western blot analysis. Eighty five per cent (23/27) of cases of pancreatic adenocarcinoma showed increased TSP-1 staining in the desmoplastic stroma adjacent to tumor cells. No specific positive staining for TSP-1 was observed in the normal pancreatic tissues and the inflammatory areas. TSP-1 localized in tumor stroma surrounding the tumor cells expressing MMP-9. Using TSP-1 competitive ELISA, the secretion of TSP-1 by different pancreatic cancer cell lines into culture medium varied from 11.45 ± 14.08 to 275.82 ± 45.56 ng/10 6 cells/24 hours. The amounts of TSP-1 detected in both culture media and cell extracts from fibroblasts or endothelial cells were at least 2-3 fold higher than those from pancreatic cancer cells. TSP-1 augmented the production of matrix metalloproteinase-9, a matrix degrading enzyme, in pancreatic cancer cells in vitro. Stromally-derived TSP-1 up-regulates the production of MMP-9 by pancreatic adenocarcinoma. These data are consistent with the conclusion that TSP-1-rich stroma is involved in regulating matrix remodeling in tumor invasion.
C1 [Qian, Xiaohua] MCP Hahnemann University, Department of PathologyPhiladelphia, Pennsylvania, USA.
[Rothman, L Vicki] MCP Hahnemann University, Department of Surgery, Broad and Vine Streets, 19102-1192 Philadelphia, Pennsylvania, USA.
[Nicosia, F Roberto] MCP Hahnemann University, Department of PathologyPhiladelphia, Pennsylvania, USA.
[Tuszynski, P George] MCP Hahnemann University, Department of Surgery, Broad and Vine Streets, 19102-1192 Philadelphia, Pennsylvania, USA.
RP Tuszynski, PG (reprint author), MCP Hahnemann University, Department of Surgery, 19102-1192 Philadelphia, USA.
EM george.tuszynski@drexel.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 251
EP 259
PG 9
ER
PT J
AU Ladanyi, A
Gallai, M
Paku, S
Nagy, OJ
Dudas, J
Timar, J
Kovalszky, I
AF Ladanyi, Andrea
Gallai, Monika
Paku, Sandor
Nagy, O Julianna
Dudas, Jozsef
Timar, Jozsef
Kovalszky, Ilona
TI Expression of a Decorin-Like Moleculein Human Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE decorin; human melanoma; mRNA; protein; TGF-beta
ID decorin; human melanoma; mRNA; protein; TGF-beta
AB Decorin, a member of the family of small leucin-rich proteoglycans, has originally been described as a secreted proteoglycan component of the connective tissues, and has been implicated in the negative regulation of cell proliferation directly or via interactions with TGF-b. It was reported to be generally absent from tumor cells. Here we show that human melanoma cell lines express a decorin-like molecule. We detected decorin mRNA by RT-PCR in 7 out 7 human melanoma lines characterized by various metastatic potential. Using polyclonal antiserum against the core protein of decorin, the typical 80-120 kD glycanated form as well as a high molecular weight aberrant version (200-210 kD) of decorin were demonstrated by Western blot technique in the culture supernatants as well as in lysates of human melanoma cells. Finally, decorin epitope was also demonstrated immunohistochemically in human melanoma xenografts, as well as in tumor cells of surgically resected melanomas but not in melanocytes of nevi.The expression of this aberrant decorin did not inhibit the in vitroor in vivogrowth of human melanoma cells, and it was independent of their metastatic potential. Human melanoma cell lines expressing aberrant decorin retained sensitivity to the antiproliferative and gelatinase-stimulatory effects of exogenous TGF-b b.
C1 [Ladanyi, Andrea] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Gallai, Monika] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Paku, Sandor] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular PathologyBudapest, Hungary.
[Nagy, O Julianna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Dudas, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Krusius T, Ruoslahti E: Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci USA 83:7683-7687, 1986.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 260
EP 266
PG 7
ER
PT J
AU Ralte, MA
Sharma, ChM
Karak, KA
Mehta, SV
Sarkar, Ch
AF Ralte, Mercy Angela
Sharma, Chand Mehar
Karak, Kumar Asis
Mehta, Singh Veer
Sarkar, Chitra
TI Clinicopathological Features, MIB-1 Labeling Index and Apoptotic Index in Recurrent Astrocytic Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE astrocytic tumors; recurrent; MIB-1 labeling index; apoptotic index; interval to recurrence; progression
ID astrocytic tumors; recurrent; MIB-1 labeling index; apoptotic index; interval to recurrence; progression
AB This is a study of 64 cases of recurrent astrocytic tumors of all four WHO grades wherein a comparative evaluation of initial vs. recurrent tumor was done with respect to histological grading, MIB-1 labeling index (LI) and apoptotic index (AI). The aim was to identify factor/s that could influence interval to recurrence and/or malignant progression. Recurrence was noted in all grades and upon recurrence, 93.3% of grade II (low grade diffuse) astrocytomas and 63.6% of grade III anaplastic astrocytomas underwent malignant progression. However, none of the Grade I tumors showed evidence of malignant progression. Though interval to recurrence varied considerably, there was a correlation with histological grade of the initial tumor in that grade I and II tumors had a significantly longer mean interval to recurrence (43 months and 54.8 months respectively) as compared to grade III and IV (glioblastoma multiforme) tumors (17.6 and 12.8 months respectively). The interval to recurrence was also longer for grade II and III tumors which showed progression on recurrence (55.3 months for Grade II->Grade III; 54 months for Grade II->Grade IV and 20.6 months for Grade III->IV) as compared to tumors which recurred to the same grade (12.5 months for Grade III->Grade III and 12.8 months for Grade IV->Grade IV). A statistically significant inverse correlation of MIB-1 LI with interval to recurrence was noted. Higher the MIB-1 LI, shorter was the interval to recurrence. Further a cut off MIB-1 LI value of 2.8% could be proposed in predicting recurrence free survival. Interestingly, MIB-1 LI of grade II tumors, which had progressed to grade IV was significantly higher than MIB-1 LI of grade II tumors which had progressed to grade III. Thus, this study establishes the potential role of MIB-1 LI of the initial tumor in determining interval to recurrence. However, apoptotic index has no role in predicting either interval to recurrence or malignant progression.
C1 [Ralte, Mercy Angela] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Karak, Kumar Asis] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Mehta, Singh Veer] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarcs@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 267
EP 278
PG 12
ER
PT J
AU Kaya, H
Ragazzini, T
Aribal, E
Guney, I
KOTILOGLU, E
AF Kaya, Handan
Ragazzini, Teresa
Aribal, Erkin
Guney, Ilter
KOTILOGLU, Esin
TI Her-2/neuGene Amplification Compared with HER-2/neu Protein Overexpression on Ultrasound Guided Core-Needle Biopsy Specimens of Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast carcinoma; FISH; immunohistochemistry; Her-2/neu
ID breast carcinoma; FISH; immunohistochemistry; Her-2/neu
AB Genomic amplification and oncoprotein overexpression of Her-2/neuwas studied on ultrasound core needle biopsy specimens of the infiltrative ductal carcinomas of the breast. We performed '' two colour '' fluorescence in situ hybridization (FISH) for Her-2/neuand chromosome 17 and compared the FISH results with the immunohistochemical overexpression of Her-2/neuprotein by 2 antibodies (DAKO HercepTest and the BioGenex monoclonal antibody AM 134-5M). Furthermore, following radical mastectomy with axillary dissection, Her-2/neustatus of the patients were compared with the well known histopathological prognostic factors such as histologic grade, tumor stage, lympho/ vascular invasion, surgical margin status and Paget’s disease. Amplification was demonstrated 27% of the cases. Her-2/neu protein overexpression was detected in 47% and 80% of the cases with CB11 and HercepTest respectively. We revealed statistically significant association between the tumor, oncoprotein expression and oncogene amplification (p<0.05). The results of our study showed that combination of IHC and FISH methods enhances the evaluation of tumor genetics at both gene and protein level for the analysis of Her-2/neuin breast carcinoma.
C1 [Kaya, Handan] Marmara University, School of Medicine, Department of Pathology, Altunizade, 81190 Istanbul, Turkey.
[Ragazzini, Teresa] University of Bologna, Department of OncologyBologna, Italy.
[Aribal, Erkin] Marmara University Hospital, Department of RadiologyIstanbul, Turkey.
[Guney, Ilter] Marmara University, School of Medicine, Department of Medical BiologyIstanbul, Turkey.
[KOTILOGLU, Esin] Marmara University, School of Medicine, Department of Pathology, Altunizade, 81190 Istanbul, Turkey.
RP Kaya, H (reprint author), Marmara University, School of Medicine, Department of Pathology, 81190 Istanbul, Turkey.
EM hkaya@superonline.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 279
EP 283
PG 5
ER
PT J
AU Croce, VM
Rabassa, EM
Price, RM
Segal-Eiras, A
AF Croce, V Maria
Rabassa, E Martin
Price, R Mike
Segal-Eiras, Amada
TI MUC1 Mucin and Carbohydrate Associated Antigens as Tumor Markers in Head and Neck Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and Neck Squamous Cell Carcinoma (HNSCC); MUCI mucin; carbohydrate associated antigens
ID Head and Neck Squamous Cell Carcinoma (HNSCC); MUCI mucin; carbohydrate associated antigens
AB An immunological analysis to study MUC1 mucin core protein and carbohydrate associated antigens as tissue tumor markers in head and neck carcinoma was performed. Twenty nine patients with the following tumor localizations were included: tongue (n=10), larynx (n=8), oral cavity (n=4), maxillary sinus (n=3), tonsillar ring (n=3) and pharynx (n=1); seven samples of epithelium obtained from normal organs at the same localizations were studied as controls. Immunohistochemical analysis was performed following standard procedures and reaction was graded according to staining intensity and distribution. From each tissue section, membrane, cytoplasmic and nuclear moieties were obtained by differential centrifugation with subsequent fractionation by density gradient centrifugation (6M guanidium chloride-CsCl); subcellular moieties and CsCl derived fractions were analyzed by immunoblotting. Monoclonal antibodies (MAbs) reacting with the core protein of MUCI (C595) and associated carbohydrate antigens were: Tn, 83D4 MAb; Lewis y antigen (Le y), C14 MAb; Lewis x antigen (Le x), KM380 MAb and sialyl Lewis x (sLe x), KM93 MAb. Statistical analysis was undertaken by Spearman rank correlation. In tumor samples, the immunohistochemical identification of MUCl core protein and associated antigens was extended; differences were found in the pattern and intensity of expression; results were corroborated by immunoblotting although in a few samples there was not coincidence between both methods. Localization, tumor mass or node involvement did not show significant differences for any of the antigens studied. Conclusions: 1) head and neck carcinoma expressed MUCI and associated carbohydrate antigens in high levels; 2) no relationship between antigenic expression and tumor status was found.
C1 [Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120, 1900 La Plata, Argentina.
[Rabassa, E Martin] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120, 1900 La Plata, Argentina.
[Price, R Mike] University of Nottingham, School of Pharmaceutical SciencesNottingham, UK.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120, 1900 La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), 1900 La Plata, Argentina.
EM as-eiras@netverk.com.ar
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Croce MV, Price MR, Segal-Eiras A: Detection and isolation of MUC 1 mucin from larynx squamous cell carcinoma. Pathol Oncol Res 2:93-99, 2000.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 284
EP 291
PG 8
ER
PT J
AU Berki, T
David, M
Bone, B
Losonczy, H
Vass, J
Nemeth, P
AF Berki, Timea
David, Marianna
Bone, Beata
Losonczy, Hajna
Vass, Janos
Nemeth, Peter
TI New diagnostic tool for differentiation of idiopathic
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hypereosinophilic syndrome; IL-5; INFg; Th1-Th2 balance; flow cytometry
ID hypereosinophilic syndrome; IL-5; INFg; Th1-Th2 balance; flow cytometry
AB The hypereosinophilic syndrome (HES) is a very rare disease, characterized by persistent eosinophilia with tissue involvement and organ dysfunction which often precedes a subsequent T cell lymphoma. Interleukin-5 secreted by a T lymphocyte subpopulation has been described in previous reports as the most important factor responsible for the prolonged lifespan of the eosinophils. The goal of the present study was to describe a fast, simple diagnostic method for the differentiation of HES and secondary eosinophilic states. Beside the surface marker analysis of peripheral blood mononuclear cells (PBMC) we measured surface bound IgE molecules on lymphocytes and eosinophil cells, intracellular cytokines (IL-5, INFg g) in CD4+ lymphocytes and eosinophil major basic protein (MBP) in eosinophils using flow cytometric detection method. The appearance of an IL-5 producing cell population with a decreased number of INFg gpositive lymphocytes was characteristic for the blood samples of HES patients. Predominance of Th2 cells with the appearance of a CD8+/CD3–/CD56+ cell population was restricted for the HES cases and could not be detected in secondary eosinophilic individuals. Our flow cytometric cytokine detection method (with parallel cell surface marker analysis) does not require cell separation or long term cell culture steps previously described for the detection of IL-5 producing cells. Therefore it seems to be a more appropriate approach for the differential diagnosis of primary and secondary eosinophilic states.
C1 [Berki, Timea] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12., H-7643 Pecs, Hungary.
[David, Marianna] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Bone, Beata] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12., H-7643 Pecs, Hungary.
[Losonczy, Hajna] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Vass, Janos] University of Pecs, Department of PathologyPecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12., H-7643 Pecs, Hungary.
RP Berki, T (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM timea.berki@aok.pte.hu
CR Bain BJ: Eosinophilic leukemias and the idiopathic hypereosinophilic syndrome Br J Haematol 95:2-9, 1996.
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Berki T, Kumanovics G, Kumanovics A, et al: Production and flow cytometric application of a monoclonal anti-glucocorticoid receptor antibody. J Immunol Methods 214:19-27, 1998.
Brugnoni D, Airo P, Rossi G, et al:A case of hypereosinophilic syndrome is associated with the expansion of a CD3- CD4+ T-cell population able to secrete large amounts of interleukin-5. Blood 87:1416-1422, 1996.
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Clutterbuck EJ, Hirst EM, Sanderson CJ: Human interleukin-5, IL- 5, regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6 and GMCSF. Blood 73:1504-1512, 1989.
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Desreumaux P:Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases. Blood 82:1553-1560, 1993.
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Kitano K, Ishikawa N, Shimodaira S, et al: Eosinophilia associated with clonal T-cell proliferation. Leukemia Lymphoma 27:335-342, 1997.
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Menssen HD, Renkl HJ, Rieder H, et al: Distinction of eosinophilic leukemia from idiopathic hypereosinophilic syndrome by analysis of Wilms’ tumor gene expression. Br J Haematol 101:325-334. 1998.
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Walsh GM: Human eosinophils: Their accumulation, activation and fate. Br J Haematol 97:701-709, 1997.
Weller PF, Bubley GJ: The idiopathic hypereosinophilic syndrome. Blood 83:2759-2779, 1994.
Weller PF: The immunobiology of eosinophils. N Engl J Med 324:1110-1118, 1991.
Yamaguchi Y, Suda T, Ohta S, et al: Analysis of the survival of mature human eosinophils: Interleukin-5 prevents apoptosis in mature human eosinophils. Blood 78:2542-2547, 1991.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 292
EP 297
PG 6
ER
PT J
AU Ribeiro-Silva, A
Luzzatto, F
Chang, D
Zucoloto, S
AF Ribeiro-Silva, Alfredo
Luzzatto, Felipe
Chang, Daniel
Zucoloto, Sergio
TI Limitations of Fine-Needle Aspiration Cytology to Diagnose Metaplastic Carcinoma of the Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE metaplastic carcinoma; breast; fine-needle aspiration
ID metaplastic carcinoma; breast; fine-needle aspiration
AB Metaplastic carcinoma is a very rare breast neoplasm that is often confused with benign and others malignant entities on both clinical and conventional histopathologic basis. Three cases of metaplastic carcinoma of breast are presented. The difficulties found on fine needle aspiration cytology and the limitations of this procedure are discussed as well the main features of this tumor.
C1 [Ribeiro-Silva, Alfredo] Sao Paulo University School of Medicine, Department of Pathology, Av. Bandeirantes, s/n – Campus Universitario Monte Alegre., 14048-900 Sao Paulo, Brazil.
[Luzzatto, Felipe] Sao Paulo University School of Medicine, Department of Pathology, Av. Bandeirantes, s/n – Campus Universitario Monte Alegre., 14048-900 Sao Paulo, Brazil.
[Chang, Daniel] Sao Paulo University School of Medicine, Department of Pathology, Av. Bandeirantes, s/n – Campus Universitario Monte Alegre., 14048-900 Sao Paulo, Brazil.
[Zucoloto, Sergio] Sao Paulo University School of Medicine, Department of Pathology, Av. Bandeirantes, s/n – Campus Universitario Monte Alegre., 14048-900 Sao Paulo, Brazil.
RP Ribeiro-Silva, A (reprint author), Sao Paulo University School of Medicine, Department of Pathology, 14048-900 Sao Paulo, Brazil.
EM ardsilva@rpa.fmrp.usp.br
CR Castella E, Gomez-Plaza MC, Urban A, et al: Fine-needle aspiration biopsy of metaplastic of the breast: Report of a case with abundant myxoid ground substance. Diagn Cytopathol 14:325- 327, 1996.
Yen H, Florentine B, Kelly LK, et al: Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report. Diagn Cytopathol 23:46-50, 2000.
Brenner RJ, Turner RR, Schiller V, et al. Metaplastic carcinoma of the breast: report of three cases. Cancer 82:1082-1087, 1998.
Park JM, Han BK, Moon WK, et al: Metaplastic carcinoma of the breast: mammographic and sonographic findings. J Clin Ultrasound 28:176-186, 2000.
Chao TC, Wang CS, Chen SC, et al: Metaplastic carcinomas of the breast. J Surg Oncol 71:220-225, 1999.
Rayson D, Adjei AA, Suman VJ, et al: Metaplastic breast cancer: prognosis and response to systemic therapy. Ann Oncol 10:413-419, 1999.
Chhieng DC, Cangiarella JF, Waisman J, et al: Fine-needle aspiration cytology of spindle cell lesions of the breast. Cancer 87:359-371, 1999.
Jebsen PW, Hagmar BM, Nesland JM: Metaplastic breast carcinoma. A diagnostic problem in fine needle aspiration biopsy. Acta Cytol 35:396-402, 1991.
Straathof D, Yakimets WW, Mourad WA: Fine-needle aspiration cytology of sarcomatoid carcinoma of the breast: a cytologically overlooked neoplasm. Diagn Cytopathol 16:242-246, 1997.
Gupta RK: Cytodiagnosis patterns of metaplastic breast carcinoma in aspiration samples: a study of 14 cases. Diagn Cytopathol 20:10-12, 1999.
Chhieng C, Cranor M, Lesser ME, et al: Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. Am J Surg Pathol 22:188-194, 1998.
Gupta RK: Fine needle aspiration cytodiagnosis of primary and metastatic squamous cell carcinoma of the breast. Acta Cytol 41:692-696,1997.
Kokufu I, Yamamoto M, Fukuda K, et al: Squamous cell carcinoma of the breast: three case reports. Breast cancer 6:63-68, 1999.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 298
EP 300
PG 3
ER
PT J
AU Kravchick, S
Cytron, Sh
Lobik, L
Altshuler, A
Kravchenko, Y
Ben-Dor, D
AF Kravchick, Sergey
Cytron, Shmuel
Lobik, Leonid
Altshuler, Alexander
Kravchenko, Yakov
Ben-Dor, David
TI Clot Retention and Spontaneous Rupture with Secondary Pneumatosis of Bladder Wall Following Routine Cystoscopy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE bladder neoplasm; cystoscopy; bladder injury; pneumatosis
ID bladder neoplasm; cystoscopy; bladder injury; pneumatosis
AB In this article we report an unusual case of spontaneous rupture of bladder wall following office-cystoscopy. It took place in a patient who suffered from low-stage highgrade carcinoma of bladder with the different aggressive behavior. Finally, he underwent radical cystectomy, which showed micropapillary carcinoma and pneumatosis within the bladder wall. The cause of the latter finding is rather puzzling and has been never reported previously.
C1 [Kravchick, Sergey] Barzialy Medical Center, Urology Department, Ha Histadrut 1, 78306 Ashkelon, Israel.
[Cytron, Shmuel] Barzialy Medical Center, Urology Department, Ha Histadrut 1, 78306 Ashkelon, Israel.
[Lobik, Leonid] Barzialy Medical Center, Urology Department, Ha Histadrut 1, 78306 Ashkelon, Israel.
[Altshuler, Alexander] Barzilay Medical Center, Department of RadiologyAshkelon, Israel.
[Kravchenko, Yakov] Barzialy Medical Center, Pathology DepartmentAshkelon, Israel.
[Ben-Dor, David] Barzialy Medical Center, Pathology DepartmentAshkelon, Israel.
RP Kravchick, S (reprint author), Barzialy Medical Center, Urology Department, 78306 Ashkelon, Israel.
CR Smith DP, Goldman SM, Fishman EK: Rupture of the urinary bladder following cystoscopic clot evacuation : report of two cases diagnosed by CT. Abdom Imaging 19:177, 1994.
Hasui Y, Osada Y, Kitada S, Nishi S: Significance of invasion to the mucosae on the progression of superficial bladder cancer. Urology 43:782, 1994.
Maranchie JK, Bouyounes BT, Zhang PL, et al: Clinical and pathological characteristics of micropapillary transitional cell carcinoma: a highly aggressive variant. J Urol 163:748, 2000.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2001
VL 7
IS 4
BP 301
EP 302
PG 2
ER
PT J
AU Sauer, R
AF Sauer, Rolf
TI Adjuvant and Neoadjuvant Radiotherapy and Concurrent Radiochemotherapy for Rectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE rectal cancer; radiotherapy; radiochemotherapy
ID rectal cancer; radiotherapy; radiochemotherapy
AB Radical surgery with negative margins remains the most important prognostic factor in the treatment of rectal cancer. Combined modality treatment is the recommended standard adjuvant therapy for patients with locally advanced rectal cancer in the USA and in Germany. During the last decade substantial progress has been made in treatment modalities: surgical management currently includes a broad spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. Specialized groups have reported excellent local control rates with total mesorectal excision (TME) alone. New and improved radiation techniques (conformal radiotherapy, intraoperative radiotherapy) and innovative schedules (protracted intravenous infusion, chronomodulated infusion) and combinations (oxaliplatin, irinotecan) of chemotherapy may have the potential to further increase the therapeutic benefit of adjuvant treatment. Moreover, the basic issue of timing of radio-(chemo-)therapy - preoperative versus postoperative - within a multimodality regimen is currently being addressed in prospective trials. Evidently, the current monolithic approaches, established by studies conducted more than a decade ago, to apply either the same schedule of postoperative radiochemotherapy to all patients with stage II/III rectal cancer or to give preoperative intensive short-course radiation according to the Swedish concept for all patients with resectable rectal cancer irrespective of tumor stage and treatment goal (e.g. sphincter preservation), need to be questioned. This review will discuss different irradiation settings in more recent and ongoing studies of perioperative radiotherapy for rectal cancer and will focus on the issue which patient should receive radiotherapy at all, and if so, how and when?
C1 [Sauer, Rolf] University of Erlangen, Department of Radiation Oncology, Universitatsstr. 27, 91054 Erlangen, Germany.
RP Sauer, R (reprint author), University of Erlangen, Department of Radiation Oncology, 91054 Erlangen, Germany.
CR NIH Consensus Conference: Adjuvant therapy for patients with colon and rectal cancer. JAMA 264:1444-1450, 1990.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 7
EP 17
PG 11
ER
PT J
AU Wheatley, ND
Campbell, E
AF Wheatley, N Denys
Campbell, Elaine
TI Arginine Catabolism, Liver Extracts and Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE arginine; arginase; arginine deiminase; arginine decarboxylase; deprivation; cell cycle checkpoints; cell death; cancer; leukemia
ID arginine; arginase; arginine deiminase; arginine decarboxylase; deprivation; cell cycle checkpoints; cell death; cancer; leukemia
AB Although it is self evident that cells will not grow in amino acid deficient medium, an observation less well appreciated is that malignant cells are particularly vulnerable to such deprivation, which can lead to their rapid demise. Indeed, the more flagrantly malignant the phenotype (anaplastic the tumor), the more susceptible the cells seem to be to deprivation. While some attempts to employ this strategy in cancer treatment have been made, the difference between normal and malignant cells should be more fully exploited as a means of selectivelyeliminating tumor cell populations. To be successful, information on differences between the normal and the deranged cell cycle engine and checkpoints, especially how these are affected by deprivation, is of crucial importance. Since it is only recently that the controls at restriction points have been elucidated, it is little surprise that earlier attempts to control tumor cell growth by limiting the availability of an essential amino acid have met with limited success. Studies havebeen sporadic and isolated, often with little more than anecdotal descriptions as far as clinical work was concerned. This review concentrates on what has been accomplished primarily in vitro and since about 1950 with regard to argininecatabolism, while recognising that other essential amino acids have also been the focus of attention by some investigators. Treatments have included medium and plasma manipulation, dietary control, enzymatic degradation, and the use of liver extracts. On some occasions, substitution of amino acid analogues has been explored. It is argued that current knowledge, combined with past experience, calls for a much closer examination of the full potential of amino acid (and specifically arginine) deprivation as a means of controlling tumor growth, with greater attention to protocols that might be used to treat human cancers.
C1 [Wheatley, N Denys] University of Aberdeen, Department of Cell Pathology, MacRobert Building, 581 King Street, AB24 5UA Aberdeen, UK.
[Campbell, Elaine] University of Aberdeen, Department of Cell Pathology, MacRobert Building, 581 King Street, AB24 5UA Aberdeen, UK.
RP Wheatley, ND (reprint author), University of Aberdeen, Department of Cell Pathology, AB24 5UA Aberdeen, UK.
EM wheatley@abdn.ac.uk
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 18
EP 25
PG 8
ER
PT J
AU Park, SH
Kim, H
Song, BJ
AF Park, Sung-Hye
Kim, Hanseong
Song, Byung-Joo
TI Down Regulation of Bcl2 Expression in Invasive Ductal Carcinomas Is Both Estrogen- and Progesterone-Receptor Dependent and Associated with Poor Prognostic Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bcl2; estrogen receptor; invasive ductal carcinoma; ductal carcinoma in situ; progesterone receptor
ID Bcl2; estrogen receptor; invasive ductal carcinoma; ductal carcinoma in situ; progesterone receptor
AB In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting mammary epithelium. The exact mechanism and the effect of the down regulation of the Bcl2 expression on breast cancer cells are not clearly defined. We compared down regulation as well as the persistent expression of Bcl2 with ER, PR, p53, and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in 11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR immunoreactive ones and 71.9 % of c-erb-B2 immnonegative ones. Seventeen cases of Bcl2 down regulated IDC had a significant correlation with ER negativity (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and histological grade (76% is grade III). However, in DCIS, no significant correlation between the Bcl2 expression and various parameters were obtained, probably due to small sample size. In conclusion, the Bcl2 expression was both ER and PR dependent and down regulation of Bcl2 in IDC was significantly correlated with poor prognostic factors.
C1 [Park, Sung-Hye] Inje University, College of Medicine, Ilsan Paik Hospital, Department of Anatomical Pathology, 2240 Daewha-dong, Ilsan-gu, 411-706 Koyang-city, Kyunggi-do, South Korea.
[Kim, Hanseong] Inje University, College of Medicine, Ilsan Paik Hospital, Department of Anatomical Pathology, 2240 Daewha-dong, Ilsan-gu, 411-706 Koyang-city, Kyunggi-do, South Korea.
[Song, Byung-Joo] Inje University, College of Medicine, Ilsan Paik Hospital, Department of General SurgeryKyunggi-do, South Korea.
RP Park, SH (reprint author), Inje University, College of Medicine, Ilsan Paik Hospital, Department of Anatomical Pathology, 411-706 Koyang-city, South Korea.
EM sunghye@ilsanpaik.ac.kr
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Silvestrini R, Veneroni S, Daidone MG, et al.: The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst 86: 499-504, 1994.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 26
EP 30
PG 5
ER
PT J
AU Hong, A
Lee, S
AF Hong, Angela
Lee, C. Soon
TI Kaposi's Sarcoma: Clinico-pathological Analysis of Human Immunodeficiency Virus (HIV) and Non-HIV Associated Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kaposi’s sarcoma; human immunodeficiency virus; HIV; neoplasia; human herpesvirus 8; HHV8
ID Kaposi’s sarcoma; human immunodeficiency virus; HIV; neoplasia; human herpesvirus 8; HHV8
AB Kaposi's sarcoma (KS) is a angioformative lesion that classically occurs in elderly Eastern European and Mediterranean males but is also common in immunosuppressed individuals particularly human immunodeficiency virus (HIV)-infected patients. This study investigates the clinical and histopathological features of 47 patients with Kaposi’s sarcoma from a teaching hospital in Sydney, Australia, in which 44 cases had adequate clinical follow-up information over a 10-year period. Most of the lesions were of late stage (37/47 cases; 79%), consisting of 11 cases of plaque stage KS and 26 cases of nodular stage KS with only 10 cases of early or patch stage KS. The majority of the HIV-positive cases (23/33; 70%) and all of the HIV-negative (14/14; 100%) cases had late stage lesions (p=0.020; X 2 -test). The histopathological features that were more common in the KS lesions of HIV-negative patients were lesional cell mitosis (p=0.0002), single cell necrosis (p=0.001), apoptosis (p=0.0001) and single cell anaplasia (p=0.0001). The KS lesions in HIV-positive patients tended to have dissecting blood vessels (14/33 cases; 42%) unlike those seen in HIV-negative patients (0/14 cases; 0%) (p=0.004). Most HIV-positive cases (30/33; 90%) were males (p=0.0068); and all these patients (33/33 cases; 100%) were <60 years old, in contrast to HIV-negative patients (1/11 cases; 9%) (p=0.0001). HIV status does not affect the occurrence of multiplicity of KS lesions. However, extracutaneous or visceral KS lesions were more likely to occur in HIV-positive patients (p=0.027). The number of cases of histologically proven KS cases has decreased markedly over the recent 5 year period of 1995-1999 (n=14), which was less than half of the number of the preceding 5 year period, 1990-1994 (n=33). In summary, there are distinct differences in the clinical and histopathological features of Kaposi’s sarcoma lesions in HIV-positive and HIV-negative patients. Despite the recent discovery of the HHV8 virus as the initiating and promoting factor of most of the KS lesions, these differences indicated that there might be different mechanisms that occur in HIV-positive and HIV-negative patients in the development of this lesion.
C1 [Hong, Angela] Royal Prince Alfred Hospital, Department of Radiation Oncology, Mis-senden Road, Camperdown, 2050 New South Wales, Australia.
[Lee, C. Soon] Royal Prince Alfred Hospital,, Department of Anatomical Pathology, Mis-senden Road, Camperdown, 2050 New South Wales, Australia.
RP Lee, S (reprint author), Royal Prince Alfred Hospital,, Department of Anatomical Pathology, 2050 New South Wales, Australia.
EM slee@csls.rpa.cs.nsw.gov.au
CR Friedman-Birnbaum R, Bergman R, Bitterman-Deutsch O, et al: Classic and iatrogenic Kaposi’s sarcoma. Histopathological patterns as related to clinical course. Am J Dermatopathol 15:523-527, 1993.
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Antman K, Chang Y: Kaposi’s sarcoma. N Engl J Med 342:1027-1038, 2000.
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Modlin RL, Crissey JT, Rea TH: Kaposi’s sarcoma. Int J Dermatol 22:443-448, 1983.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 31
EP 35
PG 5
ER
PT J
AU Akisik, E
Bavbek, S
Dalay, N
AF Akisik, Elif
Bavbek, Sevil
Dalay, Nejat
TI CD44 Variant Exons in Leukemia and Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD44; RT-PCR; leukemia; lymphoma
ID CD44; RT-PCR; leukemia; lymphoma
AB CD44 is a cell surface glycoprotein expressed on different cell types that functions in lymphocyte activation and homing, extracellular matrix adhesion and cellular migration. CD44 is encoded by a single gene composed of at least 20 exons. The standard CD44 protein (CD44S or CD44H) is the hematopoietic form of CD44 in lymphoid cells. Variant isoforms (designated from v1 to v10) are formed by addition of new exons to the extracellular domain. High levels of CD44v6 expression has been observed in some tumors and are associated with metastatic spread. The aim of the present study was to investigate and evaluate expression of the CD44v6 and v6-containing variants as a possible marker in chronic myeloid leukemia and lymphoma by reverse transcription-polymerase chain reaction. CD44 exon v6 was detected in all patients and all individuals in the control group. CD44v6-v10 mRNA was observed in 25 patients but in none of the subjects in the control group. CD44v6/v9-10, CD44v6-v7, CD44v6/v10 transcripts were detected in 11, 6, and 2 patients, respectively. CD44v6-7/v9-10 transcripts were not observed in either the patients or the healthy individuals. We conclude that CD44v6-v10 expression may be associated with hematologic malignancies.
C1 [Akisik, Elif] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
[Bavbek, Sevil] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Dalay, Nejat] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
RP Dalay, N (reprint author), Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34390 Istanbul, Turkey.
EM ndalay@istanbul.edu.tr
CR Arch R, Wirth K, Hofmann M, et al: Participation in normal immune response of a metastasis-inducing splice variant of CD44. Science 257:682-685, 1992.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 36
EP 40
PG 5
ER
PT J
AU Nagy, ZsZ
Toth, J
Nagymihaly, A
Suveges, I
AF Nagy, Zsolt Zoltan
Toth, Jeannette
Nagymihaly, Attila
Suveges, Ildiko
TI The Role of Ultraviolet-B in Corneal Healing Following Excimer Laser in situ Keratomileusis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laser in situ Keratomileusis (LASIK); Ultraviolet-B; corneal transparency; subepithelial haze; activated ker-atocytes; extracellular matrix
ID Laser in situ Keratomileusis (LASIK); Ultraviolet-B; corneal transparency; subepithelial haze; activated ker-atocytes; extracellular matrix
AB Corneal photoablation with the 193 nm argon fluorid excimer laser during photorefractive keratectomy (PRK) in high diopter range is frequently associated with subepithelial haze and consequent refractive regression due to avascular corneal wound healing. The wound healing response can be augmented by Ultraviolet-B (UV-B) exposure originating from sun or solarium. Clinically Laser in situ Keratomileusis (LASIK) even in high diopter range is associated with less subepithelial haze and regression than PRK. In an animal model, the morphologic changes of the rabbit cornea were evaluated following LASIK and secondary UV-B exposure. Light microsopic changes were found to be insignificant. Transmission electron microscopy (TEM) normal epithelium, epithelial adhesion structures and normal anterior stroma showed in the LASIK treated UV-B irradiated rabbit eyes. Around the peripheral LASIK cut, migrating keratocytes with pseudopodia were observed. Under the flap (160 µm depth) the overall stromal collagen structure was normal, some activated keratocytes and mild extracellular matrix formation within and around keratocytes were noted. Within activated keratocytes TEM showed prominent rough endoplasmic reticulum, Golgi apparatus, mitochondria and extracellular vacuoles, which showed resolution with time. These changes were much milder than in PRK treated-UV-B irradiated eyes. Secondary UV-B caused no long-term disturbance in corneal transparency in LASIK and UV-B treated rabbit eyes.
C1 [Nagy, Zsolt Zoltan] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29, 1083 Budapest, Hungary.
[Toth, Jeannette] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29, 1083 Budapest, Hungary.
[Nagymihaly, Attila] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29, 1083 Budapest, Hungary.
[Suveges, Ildiko] Semmelweis University, Department of Ophthalmology, Tomo u. 25-29, 1083 Budapest, Hungary.
RP Nagy, ZsZ (reprint author), Semmelweis University, Department of Ophthalmology, 1083 Budapest, Hungary.
CR Seiler T, Kriegerowski M, Kahle G, et al: Excimer laser keratomileusis for myopia correction. Results and complications. Klin Monatsbl Augenheilk 199:153-159, 1999.
Seiler T, Holschbach A, Derse M, et al: Complications of myopic photorefractive keratectomy with the excimer laser. Ophthalmology 101:153-160, 1994.
Tsubota K, Toda I, Itoh S: Reduction of subepithelial haze after photorefractive keratectomy by cooling the cornea. Am J Ophthalmol 115:820-821, 1993.
Nagy ZZ, Nemeth J, Suveges I, et al: Examination of subepithelial haze after photorefractive keratectomy with the ultrasound biomicroscope. Klin Monatsbl Augenheilk 209:283-285, 1996.
Durrie DS, Lesher MP, Cavanaugh TB: Classification of variable clinical response after photorefractive keratectomy for myopia. J Cataract Refract Surg 11:341-347, 1995.
Grimm B, Waring Go III, Ibrahim O: Regional variation in corneal topography and wound healing following photorefractive keratectomy. J Refract Surg 11:348-357, 1995.
Siganos DS, Katsanevaki VJ, Pallikaris IG: Correlation of subepithelial haze and refractive regression 1 month after photorefractive keratectomy. J Refract Surg 15:338-342, 1999.
Wachtlin J, Langenbeck K, Schrunder S, et al:Immunohistology of corneal wound healing after photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg 15:451-458, 1999.
Pallikaris IG, Siganos DS: Excimer laser in situ keratomileusis and photorefractive keratectomy for correction of high myopia. J Refract Corneal Surg 10:498-510, 1994.
Nagy Z Z, Hiscott P, Seitz B, et al: Ultraviolet-B enhances stromal response to 193-nm excimer laser treatment. Ophthalmology 104:375-380, 1997.
Knorz MC, Liermann A, Seiberth V, et al: Laser in situ keratomileusis to correct myopia of –6.00 to –29.00 diopters. J Refract Surg 12:575-584, 1996.
Marinho A, Pinto MC, Pinto R, et al: LASIK for high myopia: one year experience. Ophthalmic Surg Lasers 1996;27:S517-520.
Kim HM, Jung HR: Laser assisted in situ keratomileusis for high myopia. Ophthalmic Surg Lasers 1996;27:S508-511.
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McGhee CN, Craig JP, Sachdev N, et al: Functional, psychological and satisfaction outcomes of laser in situ keratomileusis for high myopia. J Cataract Refarct Surg 26:497-509, 2000.
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Wang Z, Chen J, Yang B: Comparision of laser in situ keratomileusis and photorefractive keratectomy to correct myopia from -1.25 to -6.0 diopters. J Refract Surg 13:528-534, 1997.
Corbett MC, O’Brart DP, Warburton FG, Marshall J: Biologic and environmental risk factors for regression after photorefractive keratectomy. Ophthalmology 103:1381-1391, 1996.
Fagerholm P: Wound healing after photorefractive keratectomy. J Cataract Refract Surg 26:432-447, 2000.
Fagerholm P, Hamberg-Nystrom H, Tengroth B: Wound healing and myopic regression following photorefractive keratectomy. Acta Ophthalmol Copenh 72:229-234, 1994.
Weber BA, Fagerholm P, Johansson B: Colocalization of hyaluronan and water in rabbit corneas after photorefractive keratectomy by specific staining for hyaluronan and by quantitative microradiography. Cornea 16:560-563, 1997.
Helena MC, Baerveldt F, Kim WJ, Wilson SE: Keratocyte apoptosis after corneal surgery. Invest Ophthalmol Vis Sci 39:276- 283, 1998.
Wilson SE: Keratocyte apoptosis in refractive surgery. Everett Kinsey Lecture. CLAO 24:181-185, 1998.
Podskochy A, Fagerholm P: Cellular response and reactive hyaluronan production in UV-exposed rabbit corneas. Cornea 17:640-645, 1998.
Podskochy A, Gan L, Fagerholm P: Apoptosis in UV-exposed rabbit corneas. Cornea 2000. 19:99-103.
Fitzsimmons TD, Molander N, Stenevi U, et al: Endogenous hyaluronan in corneal disease. Invest Ophthalmol Vis Sci 35:2774-2782, 1994.
Vinciguerra P, Azzolini M, Radice P, et al: A method for examining surface and interface irregularities after photorefractive keratectomy and laser in situ keratomileusis: a predictor of optical and functional outcomes. J Refract Surg 14 S204-206, 1998.
Amm M, Wetzel W, Winter M, et al: Histopathological comparision of photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg 12:758-766, 1996.
Helena MC, Meisler D, Wilson SE: Epithelial growth within the lamellar interface after in situ keratomileusis, LASIK). Cornea 16:300-305, 1997.
Wilson SE, Mohan RR, Mohan RR, et al: The corneal wound healing response: cytokine-mediated interaction of epithelium, stroma, and inflammatory cells. Progress Ret Eye Res 20:625- 637, 2001.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 41
EP 46
PG 6
ER
PT J
AU Strauss, L
Fuenzalida, M
Illanes, J
Dabancens, A
Diaz, E
Lemus, D
Guerrero, A
AF Strauss, Laura
Fuenzalida, Marcela
Illanes, Julio
Dabancens, Alfredo
Diaz, Eugenia
Lemus, David
Guerrero, Anibal
TI Effect of Sulfated Beta-cyclodextrin, a Water Soluble Cycloamylose, on the Promotion and/or Inhibition of Angiogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; cancer; sulfated b-cyclodextrin
ID angiogenesis; cancer; sulfated b-cyclodextrin
AB Previous studies have reported that sulfated b b-cyclodextrin, a naturally occurring cycloamylose built up from six to eight glucopyranose units, when administered alone promotes angiogenesis, but administered with an angiostatic steroid inhibits angiogenesis in the cick embryo bioassay. In our experiments sulfated b b-cyclodextrin has been shown to posses many properties unrelated to its classical functions in the promotion and inhibition of angiogenesis that were not previously described. We studied the angiogenic and angiostatic properties of b b-cyclodextrin in a subcutaneosus plastic sponge model in mice. We realized two set of experiments. In each set mice were randomized into five groups (n= 5 mice). The first group was treated with sulfated b b-cyclodextrin (200 ng), the second group was treated with sulfated b b-cyclodextrin (2000 ng), the third group received unsubstituted b b-cyclodextrin (2000 ng), the fourth group was treated with sulfated b b-cyclodextrin (20000 ng) and the last group was used as a control group. In all groups compounds were administered intraperitonally 4 days after subcutaneous implantation of a sterile polyvinyl sponge on day 0, controls were not treated. Cyclodextrin administered alone at low drug concentration (200 ng) promoted angiogenesis and increased the development of venules in the sponge matrix. However, cyclodextrin administered at high drug concentration (2000 and 20 000 ng) reduced the vessel index in the sponge and areas of microhemorraghes were observed. From our results we propose that b b-cyclodextrin contains both a promoter and an inhibitor of angiogenesis and that the activation of both is drug concentration dependent.
C1 [Strauss, Laura] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Fuenzalida, Marcela] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Illanes, Julio] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Dabancens, Alfredo] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Diaz, Eugenia] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Lemus, David] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
[Guerrero, Anibal] Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, 60, rue de Longchamps, F-92200 Neuilly sur Seine, France.
RP Strauss, L (reprint author), Faculty of Medicine, University of Chile, Santiago de Chile, Department of Experimental Medicine and Department of Experimental Morphology, F-92200 Neuilly sur Seine, France.
EM strauss_ewers@hotmail.com
CR Bender ML, Kaniyama M: Cyclodextrin Chemistry. Springer Verlag, Berlin, 1978.
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Boyle EA, Mangan FR: The effect of a novel, non-steroidal anti-inflammatory compound, nabumetol, BRL14777, , on cellular infiltration into 24-hour polyvinyl sponge implants in the rat , compared with some steroidal and non-steroidal antiinflammatory drugs. J Pharm Pharmacol.34:570-575, 1982
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 47
EP 53
PG 7
ER
PT J
AU Patyanik, M
Mayer,
Polgar, I
AF Patyanik, Mihaly
Mayer, Arpad
Polgar, Istvan
TI Results of Ovary Tumor Treatment With Abdominally Administered 198Au Evaluated on the Basis of Long Term Follow Up
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ovary tumor; intraperitoneal therapy; radionuclide therapy
ID ovary tumor; intraperitoneal therapy; radionuclide therapy
AB In the period between 1959 and 1980 165 patients – previously operated with ovarian tumor – were treated by intraperitoneally administered 198Au in the Oncoradiological Centre of the Uzsoki Hospital. The stage distribution of the 158 patients with common epithelial histology was as it follows: Stage I/A 31; Stage I/B 9; Stage I/C 59; Stage II/A 19; Stage II/B 11; Stage II/C 7, Stage III/A 22. The five year survival result is the next: Stage I/A 90%; Stage I/B 78%; Stage I/C 58%; Stage II/A 26%; Stage II/B 27%; Stage II/C 14%; Stage III/A 18%. From the other 7 patients six had sex cord tumor and one lipid cell tumor. The number of the side effects is in good agreement with the data in literature. The use of 198Au for intraperitoneal treatment of ovary tumors is not contemporary today because of gamma radiation of radiogold, but intraperitoneal radiation treatment should not be forgotten.
C1 [Patyanik, Mihaly] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Uzsoki utca 29, 1145 Budapest, Hungary.
[Mayer, Arpad] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Uzsoki utca 29, 1145 Budapest, Hungary.
[Polgar, Istvan] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Uzsoki utca 29, 1145 Budapest, Hungary.
RP Patyanik, M (reprint author), Fovarosi Onkormanyzat Uzsoki utcai Korhaza, 1145 Budapest, Hungary.
CR Chamberlain RH: Outline of the applicants of radioactive colloidal gold 198 to intraperioneal, intrapleural and intrathecal use. In. A preliminary manual of the properties and use of colloidal gold 198:23-31, 1951.
Currie JR, Bayne F, Harris C et al: Radioactive chromic phosphate suspension: Studies on distribution, dose, absorption and effective therapeutic radiation in phantoms, dogs and patients. Gynecol Oncol 12:193-218, 1981.
Decker DG, Webb MJ, Holbrook MA: Radiogold treatment of epithelial cancer of the ovary. Am J Obstet Gynecol 115:751- 756, 1973.
Dembo AJ: Abdominopelvic radiotherapy in ovarium cancer. A 10 year experience. Cancer 55:2285-2290, 1985.
Eltringham JR: Radiation therapy for ovarium carcinoma. Clin Obstet Gynecol 22:967-992, 1979.
Epenetos AA, Munro AJ, Steward S: Antibody-guided irradiation of advanced ovarium cancer with intraperitoneally administered radiolabelled monoclonal antibodies. J Clin Oncol 12:1890-1899, 1987.
Fletcher GM: Textbook of Radiology. Lea and Febiger, Philadelphia, 1973.
Fuks Z: Patterns of spread of ovarium carcinoma relation to therapeutic strategies. Adv Biosci 26:39-51, 1980.
Kalebi IA, et al: Radioimmunotherapy of solid cancers. Acta Oncolo 35:343-355, 1996.
Klaassen D, Shelley W, Starreveld A, et al: External beam pelvic radiotherapy plus intraperitoneal radioactive chromic phosphate in early stage ovarium cancer. A toxic combination. Int J Radiol Oncol Biol Phys 11:1801-1804, 1985.
Moor DW, Langley H: Routine use of radiogold following operation for ovarium cancer. Am J Obstet Gynecol 98:624-628, 1967.
Muller JH: Curative aim and results of routine intraperitoneal radiocolloid administration in the treatment of ovarian cancer. Am J Roentgenology, Radiat Ther Nucl Med 89:533-540, 1963.
Muller JL: Weitere Entwicklungen der Therapie von peritoneal Carcinosen bei ovarial Carcinom mit kunstlicher Radioaktivitat, 198Au). Gynecologia 129: 89-294, 1950.
Munnell EW: Is conservative therapy ever justified in Stage I, Ia, cancer of the ovary? Am J Obstet Gynecol 103:641-650, 1969.
Ozols RF: Carboplatin and Paclitaxel in ovarium Cancer. Seminars in Oncology 22: Suppl 6, 78-84, 1995.
Pagenelli G, Belloni C, Magnani P, et al: Two-step tumor targeting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidine. Eur J Nucl Med 19:322, 1992.
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Zalutsky R. et al: Radioimmuntherapy with a-particle emitting radioimunoconjugates. Acta Oncolo 35:373-379, 1996.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 54
EP 57
PG 4
ER
PT J
AU Dehaghani, SA
Amirzargar, AA
Farjadian, Sh
Ghaderi, A
AF Dehaghani, Samsami Alamtaj
Amirzargar, Ali-Akbar
Farjadian, Shirin
Ghaderi, Abbas
TI HLA-DQBl Alleles and Susceptibility to Cervical Squamous Cell Carcinoma in Southern Iranian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervix carcinoma; HLA-DQ; PCR-SSP
ID cervix carcinoma; HLA-DQ; PCR-SSP
AB The association of HLA class II with various autoimmune diseases has been extensively investigated. Despite the importance and functions of HLA genes in the evolution of cancer, the allele specific association of HLA molecules in cancer patients has not been well investigated. In this study the HLA-class II alleles frequency was investigated in Iranian patients with cervical squamous cell carcinoma. HLA typing was carried out by PCR amplification using sequence specific primers (PCR-SSP). DRB1, DQA1 and DQB1 typing was performed for 23 patients. The allele frequencies were calculated and compared with 36 healthy Iranian female controls. A positive association was observed between the existence of HLA-DQB1* 0601 and squamous cell carcinoma of the cervix (p<0.04, RR=1.94). Moreover, analysis of HLA-DRB1, DQA1 and DQB1 haplotypes indicated that none of the putative haplotypes were significantly associated with either patient or control group. Positive association of cervical carcinoma with a single allele of HLA-DQ provides evidence on the importance of HLA class II molecules and the immune response in squamous cell carcinoma of cervix.
C1 [Dehaghani, Samsami Alamtaj] Shiraz University of Medical Sciences, Department of Obstetrics and GynecologyShiraz, Iran.
[Amirzargar, Ali-Akbar] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Farjadian, Shirin] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Ghaderi, A (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM ghaderia@sums.ac.ir
CR Torres LM, Cabrera T, Concha A, et al: HLA class I expression and HPV-16 sequences in premalignant and malignant lesions of the cervix. Tissue Antigens 41:65-71, 1993.
Reid R: Immunology and Immunotherapy. In: practical Gynecology Oncology. 1st Edition. Williams and Wilkins Co, 1989.
Wank R, Thomssen C: High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352:723-725, 1991.
Glew SS, Stern PL, Davidson JA, Dyers PA: HLA antigens and cervical carcinoma. Nature 356:22, 1992.
Gregoire L, Lawrence WD, Kukuruga D, et al: Association between HLA-DQB 1 alleles and risk for cervical cancer in African-American women. Int J Cancer 57:504-507, 1994.
Nawa A, Nishiyama Y, Kobayashi T, et al:Association of human leukocyte antigen-DQB1*03 with cervical cancer in Japanese women aged 35 years and younger. Cancer 75:518-521, 1995.
Vandenvelde C, De Foor M, Van Beers D: Precision about the association between cervical carcinoma and HLA-DQBl*03 alleles. Lancet 342:553, 1993.
Wank R, Meulen JT, Luande J, et al: Cervical intraepithelial neoplasia, cervical carcinoma and risk for patients with HLADQB1* 0602, *0301, *0303 alleles. Lancet 341:1215, 1993.
Odunsi K, Terry G, Ho L, et al: Susceptibility to human papillomavirus- associated cervical intra-epithelial neoplasia is determined by specific HLA-DR-DQ alleles. Int J Cancer 67:595-602, 1996.
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Olerup O, Zetterquist H: HLA-DR typing by PCR amplification with sequence-specific primers, PCR-SSP, in 2 hours: an alternative to serological DR-typing in clinical practice including donor-recipient matching in cadaveric Transplantation. Tissue Antigens 39:225-235, 1992.
Zetterquest H, Olerup O: Identification of the HLA-DRB1*04, DRB1*07 and DRB1*09 alleles by PCR amplification with sequence-specific primers, PCR-SSP, in 2 hours. Hum Immunol 34:64-74, 1992.
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Naruse TK, Matsuzawa Y, Ota M, et al: HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis. Tissue Antigens 56:52-57, 2000.
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Montoya L, Saiz I, Rey G, et al: Cervical carcinoma: human papillomavirus infection and HLA-associated risk factors in the Spanish population. Eur J Immunogenet 25:329-37, 1998.
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Neuman RJ, Huettner PC, Li L, et al: Association between DQB 1 and cervical cancer in patients with human papillomavirus and family controls. Obstet Gynecol 95:134-140, 2000.
Amirzargar A, Mytilineos J, Farjadian Sh, et al: HLA Class-II allele frequencies and haplotype association in Iranian normal population. Hum Immunol 62:1234-1238, 2001.
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zur Hausen H, Schneider A: The role of papillomaviruses in human anogenital cancer. In: The papovaviridae: the papillomaviruses, eds. Salzman NP, and Howley PM, Vol: 2, pp. 245- 263, Plenum Press, New York, 1987.
Farahmandbeigi M: The incidence rate of registered cancer in Fars province. Disease Control Unit, Shiraz University Press, Iran, 2000.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 58
EP 61
PG 4
ER
PT J
AU Bhurgri, Y
Hasan, HSh
Pervez, Sh
Kayani, N
Hussainy, ShA
Muzaffar, S
Khurshid, M
AF Bhurgri, Yasmin
Hasan, H Sheema
Pervez, Shahid
Kayani, Naila
Hussainy, Shah Akbar
Muzaffar, Suhail
Khurshid, Mohammad
TI Large-Scale Pathology-Based Cancer Data - a Reflection of Population-Based Cancer Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; pathology
ID cancer; pathology
AB Pathology-based cancer data is a high quality reflection of the patterns of cancer in the population it represents, provided the demographic details of the patients are carefully recorded. Relative frequency data is neither a replacement for population-based data nor a suggested alternative; it simply enhances the quality of population data and in very large data sets reflects the cancer patterns observed in the representative populations. Aware of the standard shortfalls of pathology-based data, the department of pathology, ‘The Aga Khan University Hospital’ (AKUH) standardized its data, representing 53.4% of the cancer data of Karachi Division (Pakistan) and also reflecting the cancer pattern of other provinces of Pakistan. This data was compared with 4 different population and institutional-based data sets. The findings substantiate the observation that ''despite the problems of interpretation of data from pathology laboratories, they are an invaluable source of information on cancer patterns in much of the world where incidence data are unavailable''. If developing countries, unable to organize National Population- Based Registry should as an alternate develop National Pathology-based Registers a well targeted and monitored, a Cancer Control Program would be possible. A good quality, large-scale pathology data with demographic details of the patient recorded can also be extended to give coverage to the population.
C1 [Bhurgri, Yasmin] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Hasan, H Sheema] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Kayani, Naila] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Hussainy, Shah Akbar] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Muzaffar, Suhail] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
[Khurshid, Mohammad] The Aga Khan University, Department of Pathology and Microbiology, Stadium Rd., 74800 Karachi, Pakistan.
RP Bhurgri, Y (reprint author), The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
CR Parkin DM: Cancer Occurrence in Developing Countries. IARC Technical Report No. 75. IARC Lyon, 1986.
Bhurgri Y., Bhurgri A., Hassan SH, et al:Cancer Incidence in Karachi, Pakistan: First Results from Karachi Cancer Registry. Int. J. Cancer 85:325-329, 2000.
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Bhurgri Y: Epidemiology of Cancers in Karachi 1995-1999, KCR Technical Report No. 5; Karachi Cancer Registry, 2001.
Jensen OM, Parkin DM, MacLennan R, et al, eds.): Cancer Registration: Principles and Methods;IARC Scientific Publications No. 95 Lyon IARC, 1991.
Parkin DM, Chen VW, Ferley J,(eds.): Comparability and Quality Control in Cancer Registration, IARC Technical Report No.19, Lyon IARC, 1994.
WHO, International Classification of Diseases for Oncology, Ed. 2, Geneva, WHO 1990.
Rothwell DJ, ed.): Systemic Nomenclature of Medicine, SNOMED, microglossary for surgical pathology, College of American Pathologists, Library of Congress Number: 80, 68528 WHO, 1992, International Classification of Diseases, 10th Revision, Geneva, WHO 1992.
Census Bulletin-1, Population and Housing Census of Pakistan 1998, Population Census Organisation Statistics division, Federal Bureau of Statistics, Government of Pakistan, 1998.
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Jafarey NA: Betel quid, betel nuts and other chewing habits. Postgradu Doctor Africa 15:42-440, 1994.
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Sankaranarayanan R, Duffy SW, Padmakumari G, et al: Tobacco chewing, alcohol and nasal stuff in cancer of the gingiva in Kerala, India. Br J Cancer 60:638-643, 1989.
Sankaranarayanan R, Duffy SW, Padmakumari G, et al:. Risk factors for cancer of the buccal and labial mucosa in Kerala, Ind J Epidemiol Comm Health 13:286-292, 1990.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 62
EP 67
PG 6
ER
PT J
AU Gombas, P
Skepper, NJ
Hegyi, L
AF Gombas, Peter
Skepper, N Jeremy
Hegyi, Laszlo
TI The Image Pyramid System - an Unbiased, Inexpensive and Broadly Accessible Method of Telepathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE education; image pyramid; remote consultation; telemedicine; telepathology
ID education; image pyramid; remote consultation; telemedicine; telepathology
AB Although computerised information technology, including the Internet is broadly used and globally accessible it is still not a significant form of professional communications in diagnostic histopathology. The high cost of interactive dynamic telepathology systems makes their use limited outside the richest economies. In contrast static telepathology systems are relatively cheap but in practice their information content can be heavily biased by the choice of images sent by the consulting pathologist. The degree of this bias may be regarded simply as the amount of information transferred to a remote location expressed as a percentage of the total information present in the histological sample. We refer to this as the percentage of explicit versus implicit information. Another major source of bias may be found in the information transmitted in written or verbal discussion with a remote consultant. We have developed a system of static telepathology, the image pyramid, which attempts to minimise bias by transferring all of the information in a section to the consultant. It is inexpensive and should prove to be widely accessible.
C1 [Gombas, Peter] Military Hospital, Department of Pathology, Varosligeti Fasor 9-11, H-1071 Budapest, Hungary.
[Skepper, N Jeremy] University of Cambridge, Department of Anatomy, Multi-Imaging Centre, CB2 3DY Cambridge, UK.
[Hegyi, Laszlo] University of Cambridge, Department of Medicine, Addenbrooke’s Hospital, Level 6, ACCI, Hills Road, CB2 2QQ Cambridge, UK.
RP Gombas, P (reprint author), Military Hospital, Department of Pathology, H-1071 Budapest, Hungary.
EM pgombas@bm.gov.hu
CR Weinstein RS, Bloom KJ, Rozek LS: Telepathology and the networking of pathology diagnostic services. Arch Pathol Lab Med 111:646-652, 1987.
Kayser K, Szymas J, Weinstein R: Telepathology. Telecommunication, Electronic Education and Publication in Pathology., 1st ed). Springer Verlag: Berlin, 97-150, 1999.
Wells CA, Softer C: Telepathology: a diagnostic tool for the millennium? J Pathol 191:1-7, 2000.
Raggett J, Bains W: Artificial Intelligence from A to Z. Chapman and Hall, London. 1992.
Martin E, Dusserre P, Fages A, et al: Telepathology: a new tool of pathology? Presentation of a French national network. Zentralbl Pathol 138:419-423, 1992.
Kayser K, Oberholzer M, Weisse G, et al: Long distance image transfer: First results of its use in histopathological diagnosis. APMIS 99:808-814, 1991.
Kayser K, Drileck M, Rahn W: Aids of telepathology in intraoperative histomorphological tumor diagnosis and classification. In Vivo 7:395-398, 1993.
Eide TJ, Nordrum I: Current status of telepathology. APMIS 102:881-890, 1994.
Weinstein RS, Bhattacharyya AK, Graham AR, et al: Telepathology: a ten-year progress report. Hum Pathol 28:1-7, 1997.
Gombas P, Szende B, Stotz G: Future aspects and benefits of telematic networks used in pathology for countries of central Europe, CCE). Elec J Pathol Histol; 2:963-968, 1996.
Schubert E, Gross W, Siderits RH, et al: A pathologist-designed imaging system for anatomic pathology signout, teaching, and research. Semin Diagn Pathol 11:263-73, 1994.
Bashshur RL: Telemedicine effects: cost, quality, and access. J Med Syst 19: 81-91, 1995.
Halliday BE, Bhattacharyya AK, Graham AR, et al: Diagnostic accuracy of an international static-imaging telepathology consultation service. Hum Pathol 28:17-21. 1997.
Viellefond A, Staroz F, Fabre M, et al: Martin-Pop V, Martin E, Got C, Franc B. Reliability of the anatomopathological diagnosis by static image transfer. Arch Anat Cytol Pathol 43:246-50, 1995.
Callas PW, Leslie KO, Mattia AR, et al: Diagnostic accuracy of a rural live video telepathology system. Am J Surg Pathol 21:812-819, 1997
Dunn BE, Almagro UA, Choi H, et al: Dynamic-robotic telepathology. Department of Veterans Affairs feasibility study. Hum Pathol 28:8-12, 1997.
Poremba C, Pickhardt N: Economic evaluation of telepathology. Pathologe 19: 18-24, 1998.
Sowter C, Wells CA: Telepathology: assessment of the implications and applications of telepathology for practical diagnostic pathology. [editorial ] J Clin Pathol 51: 14-715, 1998.
Petersen I, Wolf G, Roth K, Schluns K: Telepathology by the Internet. J Pathol 191:8-11, 2000.
Weinstein RS, Bloom KJ, Krupinski EA et al: Human performance studies of the video microscope component of a dynamic telepathology system. Zentralbl Pathol 138:399-403, 1992.
Mairinger T, Netzer TT, Schoner W et al:. Pathologist’ attitudes to implementing telepathology. J Telemed Telecare 4:41-46, 1998.
Weinberg DS, Allaert FA, Dussere P et al: Telepathology diagnosis by means of digital still images: an international validation study. Hum Pathol 27: 111-118, 1996.
Weinstein RA: Futurist meets the 21 century: love at first sight [editorial ] Hum Pathol 31: 1-2, 2000.
Katt EC, Dennis SE: Web-based pathology education. Arch Pathol Lab Med 122:745-749, 1998.
Kayser K, Kayser G. Recent development of telepathology in Europe with specific emphasis on quality assurance. Anal Quant Cytol Histol 21:319-21, 1999.
Gombas P, Skepper JN, Hegyi L: The Image Pyramid – digital slide in the surgical pathology. http://ultra.obuda.kando.hu/~medinfo/tp/ 2001.
Gombas P: Informational aspects of telepathology on routine surgical pathology Anal Cell Pathol 21:141-147, 2000.
Harris T, Leaven T, Heidger P, Kreiter C: Comparison of a virtual microscope laboratory to a regular microscope laboratory for teaching histology Anat Rec 265:10-4, 2001.
Leong FJ, J. McGee JO: Automated complete slide digitization: a medium for simultaneous viewing by multiple pathologists. J Pathol 195:508-514, 2001.
Saltz HJ: Digital Pathology – The big picture Hum Pathol; 2000; 31:779-780.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 68
EP 73
PG 6
ER
PT J
AU Cserni, G
AF Cserni, Gabor
TI
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE ductal carcinoma in situ (DCIS); solid papillary carcinoma; breast cancer; revertant DCIS
ID ductal carcinoma in situ (DCIS); solid papillary carcinoma; breast cancer; revertant DCIS
AB A case of invasive carcinoma of mixed papillary and not otherwise specified ductal type with areas of solid papillary ductal carcinoma in situ(DCIS) is reported. The solid papillary areas were predominantly of low nuclear grade, but a small area of intermediate-grade solid papillary neoplasm was also seen within the tumor, together with an area suggestive of microinvasion. The massive regional nodal tumor load consisted of invasive papillary carcinoma and revertant low-grade solid papillary carcinoma with no myoepithelial cells around the circum-scribed solid papillary areas. This is the first report of a solid papillary pattern simulating intraductal carcinoma in lymph nodes, and the first time that a solid papillary carcinoma is reported in association with invasive papillary carcinoma. The case suggests that mammary carcinomas with a solid papillary pattern may sometimes be of higher grade than usual, and do not always represent a DCIS, but may be invasive.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Barsky SH, Bose S: Should LCIS be regarded as a heterogeneous disease? Breast J 5:407-412, 1999.
Barsky SH, Doberneck SA, Sternlicht MD, et al: “Revertant” DCIS in human axillary breast carcinoma metastases. J Pathol 183:188-194, 1997.
Buerger H, Otterbach F, Simon R, et al: Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 189:521-526, 1999.
Capella C, Eusebi V, Mann B, et al: Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 4:613-630, 1980.
Cross AS, Azzopardi JG, Krausz T, et al: A morphological and immunohistochemical study of a distinctive variant of ductal carcinoma in situ of the breast. Histopathol 9:1-37, 1985.
Diest PJ van: Ductal carcinoma in situ in breast carcinogenesis. J Pathol 187:383-384, 1999.
Douglas-Jones AG, Gupta SK, Attanoos RL, et al: A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast, DCIS): correlation with grade of associated invasive carcinoma. Histopathol 29: 97-409, 1996.
Ellis IO, Eslton CW, Poller DN: Ductal carcinoma in situ. In: Elston CW, Ellis IO, Eds, The Breast, Systemic Pathology, Volume 13, 3rd ed., pp 249-281. Churchill Livingstone, Edinburgh, 1998.
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Lampejo OT, Barnes DM, Smith P, et al: Evaluation of infiltrating carcinomas with a DCIS component: correlation of the histologic type of the in situ component with the grade of the infiltrating component. Semin Diagn Pathol 11: 215-222, 1994
Lee AHS, Telfer TP, Millis RR: Metastatic breast carcinoma with appearance resembling micropapillary ductal carcinoma in situ. J Clin Pathol 48:380-382, 1995.
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Yaziji H, Gown AM, Sneige N: Detection of stromal invasion in breast cancer: the myoepithalial markers. Adv Anat Pathol 7:100- 109, 2000.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2002
VL 8
IS 1
BP 74
EP 77
PG 4
ER
PT J
AU Dank, M
AF Dank, Magdolna
TI The Role of Aromasin in the Hormonal Therapy of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE exemestane; aromasin; hormonal therapy; breast cancer
ID exemestane; aromasin; hormonal therapy; breast cancer
AB In the last 40 years tamoxifen and progestogens constituted the basis of hormonal therapy. Introduction of the third generation, selective, anti-aromatase agents added effective drugs of good tolerability to the anti-cancer armamentarium. Exemestane, an oral steroidal-type aromatase inhibitor - which irreversibly blocks aromatase - is very effective in the treatment of metastatic breast cancer. As a second line therapy, exemestane is more effective and causes less side effects than megestrol-acetate. Its administration as first line therapy gave promising results. The role of exemestane in adjuvant treatment has not yet been soundly established but trials are ongoing. It may be effective as neoadjuvant treatment in selected groups of patients. Future studies will clarify exemestane’s role in chemoprevention and in the treatment of post-menopausal women administered together with cytostatic agents.
C1 [Dank, Magdolna] Semmelweis University, Department of Radiology and Oncotherapy, Ulloi ut 78a, H1082 Budapest, Hungary.
RP Dank, M (reprint author), Semmelweis University, Department of Radiology and Oncotherapy, H1082 Budapest, Hungary.
EM danke@radi.sote.hu
CR Buzdar A, Howell A: Advances in aromatase inhibition: Clinical efficacy and tolerability in the treatment of breast cancer. Clin Cancer Res 7:2620-2635, 2001.
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Shenton KC, Dowsett M, Lu Q, et al: Comparison of biochemical activity with aromatase immunhistochemistry in human breast carcinoma. Breast Cancer Res Treat 49:S101-S107,1998.
Brueggemeier RW: Aromatase inhibitors - mechanisms of steroidal inhibitors. Breast Cancer Res Treat 30:31-42,1994.
Brodie AM, Garrett WM, Hendrickson JR, et al: Inactivation of aromatase in vitro by 4-hydroxy-androstene-3,17-dione and 4- acetaxy-4-androstene-3,17-dione and sustained effects in vitro. Steroids 38:693-702, 1981.
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Geisler J, King N, Anker G, et al: In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor in postmenopausal breast cancer patients. Clin Cancer Res 4:2089-2093, 1994.
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Jones S, Belt R, Cooper B: A phase II study of antitumor efficacy and safety of exemestane, EXE, as a second line hormonal treatment of postmenopausal patients with metastatic breast cancer, MBC, refractory to tamoxifen, Tam, San Antonio Breast Conference, 1998A
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Dixon M, Anderson T, Miller WR: Phase IIb study of neoadjuvant exemestan in locally advanced breast cancer. ASCO Abstr 1908, 2001.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 87
EP 92
PG 6
ER
PT J
AU Esik, O
Tusnady, G
Tron, L
Boer, A
Szentirmay, Z
Szabolcs, I
Racz, K
Lengyel, E
Szekely, J
Kasler, M
AF Esik, Olga
Tusnady, Gabor
Tron, Lajos
Boer, Andras
Szentirmay, Zoltan
Szabolcs, Istvan
Racz, Karoly
Lengyel, Erzsebet
Szekely, Judit
Kasler, Miklos
TI Markov Model-based Estimation of Individual Survival Probability for Medullary Thyroid Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE medullary thyroid carcinoma; prognosis; multivariate analysis; Markov model; individual survival probability; MEDUPRED
ID medullary thyroid carcinoma; prognosis; multivariate analysis; Markov model; individual survival probability; MEDUPRED
AB The relatively benign, but occasionally rapidly fatal clinical course of medullary thyroid cancer (MTC) has raised the need for individual survival probability estimation. A retrospective study on 91 MTC clinical case histories with a mean follow-up of 6 years indicated prevalences of local, regional and distant residual tumor on primary care completion of 23%, 54% and 54%, respectively. Local, regional and distant relapses during follow-up occurred in 8%, 23% and 26% of the patients, with a cause-specific death in 26% of the cases. Prognostic factors statistically significantly influencing the cause-specific survival were selected by uni- and multivariate analysis. A Markov method-based model was developed for the estimation of individual time-dependent local, regional and distant relapse-free and cause-specific survival probability functions, with parameters numerically determined via a maximum likelihood procedure. These parameters include relative risk factors related to prognosticators, a residual or recurrent local/regional/distant tumor, and combinations of these entities. In multivariate studies, the patient’s age and gender, the genetic basis of the dis-ease, lymph node involvement, the existence of a general symptom (diarrhoea) at presentation, and the dosage of external irradiation proved to be prognosticators. The cause-specific survival function of the study population indicated mean 5, 10 and 15-year survival probabilities of 69%, 62% and 58%. CONCLUSION: Survival probabilities can be predicted for extrastudy cases provided that the same laws and principles govern the clinical course of these cases and those comprising the study. For individual survival probability estimation, a Pascal program (MEDUPRED) was written and is available on the home page of the National Institute of Oncology, Budapest (www.oncol.hu).
C1 [Esik, Olga] Semmelweis University, Department of OncologyBudapest, Hungary.
[Tusnady, Gabor] Hungarian Academy of Sciences, Renyi Alfred Mathematical InstituteBudapest, Hungary.
[Tron, Lajos] University of Debrecen, PET CenterDebrecen, Hungary.
[Boer, Andras] National Institute of Oncology, Department of Head and Neck SurgeryBudapest, Hungary.
[Szentirmay, Zoltan] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Szabolcs, Istvan] National Health Centre, Department of EndocrinologyBudapest, Hungary.
[Racz, Karoly] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Lengyel, Erzsebet] National Institute of Oncology, Center of Radiotherapy, H-1122 Budapest, Hungary.
[Szekely, Judit] National Institute of Oncology, Center of Radiotherapy, H-1122 Budapest, Hungary.
[Kasler, Miklos] National Institute of Oncology, Department of Head and Neck SurgeryBudapest, Hungary.
RP Esik, O (reprint author), Semmelweis University, Department of Oncology, Budapest, Hungary.
CR Anderson PK, Borgan O, Gill RD, et al: Statistical models based on counting processes. Springer Verlag, Berlin-Heidelberg- New York-London-Paris-Tokyo-Hong Kong-Barcelona- Budapest, 1992.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 93
EP 104
PG 12
ER
PT J
AU Pasquale, AM
Weppler, D
Smith, J
Icardi, M
Amador, A
Gonzalez, M
Tomoaki, K
Tzakis, A
Ruiz, P
AF Pasquale, A Melissa
Weppler, Debbie
Smith, Jon
Icardi, Michael
Amador, Alexandra
Gonzalez, Monica
Tomoaki, Kato
Tzakis, Andreas
Ruiz, Phillip
TI Burkitt's Lymphoma Variant of Post-transplant Lymphoproliferative Disease (PTLD)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PTLD; Burkitt’s lymphoma
ID PTLD; Burkitt’s lymphoma
AB The occurrence of posttransplant lymphoproliferative disorder (PTLD) in solid organ allograft recipients can be quite varied in clinical presentation, histopathological characteristics and frequency. A variety of lymphomas can develop as a PTLD although some types appear infrequently and remain poorly understood in this clinical setting. In this report, we describe two cases of Burkitt’s lymphoma presenting as a PTLD following liver transplantation. The recipients were 12 and 44 years of age and displayed gastrointestinal involvement by the tumors several years following transplant. The tumors displayed the typical histological features of Burkitt’s lymphoma and were markedly positive for EBV. The tumors displayed similar immunophenotypic characteristics by flow cytometry and had rearrangements of the immunoglobulin J-H heavy chain. The tumors required aggressive chemotherapy and a cessation of immunosuppressive therapy. This report demonstrates that Burkitt’s type lymphomas can develop in the posttransplant setting and that these tumors contain morphologic, cytofluorographic and molecular features identical to Burkitt’s lymphomas that occur in non-transplant patients. Our experience is that these PTLD- Burkitt’s lymphomas behave aggressively and require intensive chemotherapeutic intervention.
C1 [Pasquale, A Melissa] University of Miami, Department of Pathology, Jackson Memorial Hospital - Holtz Center, Room 2101, 33136 Miami, Florida, USA.
[Weppler, Debbie] University of Miami, Department of SurgeryMiami, Florida, USA.
[Smith, Jon] University of Miami, Department of Pathology, Jackson Memorial Hospital - Holtz Center, Room 2101, 33136 Miami, Florida, USA.
[Icardi, Michael] University of Miami, Department of Pathology, Jackson Memorial Hospital - Holtz Center, Room 2101, 33136 Miami, Florida, USA.
[Amador, Alexandra] University of Miami, Department of Pathology, Jackson Memorial Hospital - Holtz Center, Room 2101, 33136 Miami, Florida, USA.
[Gonzalez, Monica] University of Miami, Department of SurgeryMiami, Florida, USA.
[Tomoaki, Kato] University of Miami, Department of SurgeryMiami, Florida, USA.
[Tzakis, Andreas] University of Miami, Department of SurgeryMiami, Florida, USA.
[Ruiz, Phillip] University of Miami, Department of Pathology, Jackson Memorial Hospital - Holtz Center, Room 2101, 33136 Miami, Florida, USA.
RP Ruiz, P (reprint author), University of Miami, Department of Pathology, 33136 Miami, USA.
EM pruiz@med.miami.edu
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Cacciarelli TV, Green M, Jaffe R, et al: Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus, FK506, therapy. Transplantation 66:1047-1052, 1998.
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Harris NL, Ferry JA, Swerdlow SH: Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop. Semin Diag Pathol 1997;14(1):8-14.
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Leblond V, Sutton L, Dorent R, et al: Lymphoproliferative disorders after organ transplantation: a report of 24 cases observed in a single center. J Clin Oncol 13:961-968, 1995.
Frank D, Cesarman E, Lie YF, et al: Posttransplantation lymphoproliferative disorders frequently contain Type A and not Type B Epstein-Barr virus. Blood 85:1396-1403, 1995.
Walker RC, Paya, CV, Marshall WF, et al: Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and othe rsolid organ transplantations. J Heart Lung Transplant 14:214-221, 1995.
Harris NL, Jaffe ES, Diebold J, et al: World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology 36:69-86, 2000.
Berard, et al. Histopathological definition of Burkitt’s Tumour. Bull WHO 40:601-607, 1969.
Cossman J, Uppenkamp M, Sundeen J, et al: Molecular genetics and the diagnosis of lymphoma. Arch Pathol Lab Med 112:117-127, 1988.
Wu TC, Mann RB, Epstein JI, et al: Abundant expression of EBER1 am11 nuclear RNA in nasopharyngeal carcinoma, a morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol 46:1310-1313, 1991.
Rea D, Fourcade C, Leblond V, et al: Epstein-Barr virus latent and replicative gene expression in posttransplant lymphoproliferative disorders and AIDS-related non-Hodgkin’s lymphomas. Ann Oncol 5, Suppl 1): S113-S116, 1994.
Cen H, Williams PA, McWilliams HP, et al: Evidence of restricted Epstein-Barr virus latent gene expression and anti- EBNA antibody response in solid organ transplant recipients with posttransplant lymphoproliferative disorders. Blood 81:1393-1403, 1993.
Smets F, Vajro P, Cornu G, et al: Indications and results of chemotherapy in children with posttransplant lymphoproliferative disease after liver transplantation. Transplantation 69:982- 984, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 105
EP 108
PG 4
ER
PT J
AU Teni, T
Pawar, S
Sanghvi, V
Saranath, D
AF Teni, Tanuja
Pawar, Sagar
Sanghvi, Vikram
Saranath, Dhananjaya
TI Expression of Bcl-2 and Bax In Chewing Tobacco-Induced Oral Cancers and Oral Lesions from India
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bcl-2; bax; p53; oral cancer; oral lesions; immunohistochemistry
ID bcl-2; bax; p53; oral cancer; oral lesions; immunohistochemistry
AB Deregulation of oncogenes and tumor suppressor genes involved in apoptosis has been associated with tumor development and progression. To investigate the involvement of apoptosis regulating proteins in oral cancer in Indian patients, primarily associated with chewing tobacco habits, immunohistochemical expression of bcl-2 and bax was examined in 63 oral squamous cell carcinomas, and 31 putative premalignant lesions. Our studies revealed overexpression of tumor specific cytoplasmic bcl-2 in 56% and bax in 43% oral cancers. The oral cancers in the Indian patients are preceded by premalignant oral lesions; hence oral lesions were examined for bcl-2 and bax expression. We observed aberrant expression of bcl-2 in 16% oral lesions comprising leukoplakias and SMF and bax in 55% oral lesions. We have already reported, p53 expression in these oral cancers and lesions. It was noteworthy that 30% oral cancers demonstrated a p53+bcl2+ pattern, and 14% samples exhibited p53+bcl2+bax+ pattern. However, none of the oral lesions showed concurrent deregulation of p53 and bcl-2 or all the three genes. Interestingly 45% oral lesions were p53-bax+ as compared to 18% oral cancers; while 39% oral lesions were bcl2-bax+ as compared to 14% oral cancers, indicating overexpression of bax in oral lesions, in the absence of p53 and bcl-2 proteins. Significant correlation was observed between positive nodal status and bcl2+ (p=0.047) and p53+bcl-2+ (p=0.01) in oral cancers. Kaplan Meier survival analysis showed significantly (p=0.059) higher survival in patients with p53- oral tumors than with p53+ tumors. Our studies thus indicate frequent overexpression of apoptosis regulators bcl-2, bax and p53 proteins in oral cancers, and a subset of oral lesions, representing early events in oral car-cinogenesis. The aberrant bcl-2 expression and loss of p53 function observed, may play an important role in the tumorigenesis of oral cancers by allowing escape from apoptosis and enabling additional genetic alterations to accrue.
C1 [Teni, Tanuja] Tata Memorial Centre, Cancer Research Institute, Laboratory of Cancer Genes, Jaslok Hospital and Research Centre, 15, Dr.G.Deshmukh Marg, 400026 Parel, Mumbai, India.
[Pawar, Sagar] Tata Memorial Centre, Cancer Research Institute, Laboratory of Cancer Genes, Jaslok Hospital and Research Centre, 15, Dr.G.Deshmukh Marg, 400026 Parel, Mumbai, India.
[Sanghvi, Vikram] Tata Memorial Hospital, Tata Memorial Centre, Department of SurgeryParel, Mumbai, India.
[Saranath, Dhananjaya] Tata Memorial Centre, Cancer Research Institute, Laboratory of Cancer Genes, Jaslok Hospital and Research Centre, 15, Dr.G.Deshmukh Marg, 400026 Parel, Mumbai, India.
RP Saranath, D (reprint author), Tata Memorial Centre, Cancer Research Institute, Laboratory of Cancer Genes, 400026 Parel, India.
EM dsaranath@jaslokhospital.net
CR Moore SR, Johnson NW, Pierce AM, Wilson DF: The epidemiology of mouth cancer: a review of global incidence. Oral Diseases 6:65-74, 2000.
National Cancer Registry Programme: Consolidated Report of the Population Based Cancer Registries : 1990–1996, Incidence and Distribution of Cancer under the ICMR, New Delhi, August 2001.
Gupta PC, Bhonsle RB, Murti PR, et al: An epidemiological assessment of cancer risk of oral precancerous lesions in India with special reference to nodular leukoplakia. Cancer 63:2247- 2251, 1989.
Tradati N, Grigolat R, Calabrase L, et al : Oral leukoplakia to treat or not? Oral Oncol 33:317- 321, 1997.
Saranath D, Panchal RG, Nair R, et al: Oncogene amplification in squamous cell carcinoma of the oral cavity. Jpn J Cancer 80:430-437, 1989.
Saranath D, Panchal RG, Nair R, et al: Amplification and overexpression of epidermal growth factor receptor in human oropharyngeal cancer. Eur J Cancer B Oral Oncol. 28:139-143, 1992.
Saranath D, Chang SE, Bhoite LT, et al: High frequency mutation in codon 12 and 61 of H-ras oncogene in chewing tobacco related human oral carcinomas in India. Br J Cancer 63:573- 578, 1991.
Saranath D, Bhoite LT, Mehta AR, et al: Loss of allelic heterozygosity at the Harvey locus in human oral carcinomas. J Cancer Res Clin Oncol. 117:483-488, 1991.
Saranath D, Bhoite LT and Deo MG: Molecular lesions in human oral cancer: the Indian scene. Eur J Cancer Oral Oncol. 29:107-112,1993.
Tandle A and Saranath D: Genetic alterations on chromosome 3, p53 tumor suppressor gene and telomerase activity in oral cancers from India. Asian Pacific Journal of Cancer Prevention, Vol. I APCC Supplement 219-225, 2000.
Mahale A and Saranath D: Microsatellite alterations on chromosome 9 in chewing tobacco -induced oral cell carcinomas from India. Oral Oncol 36:199-206, 2000. 12 Saranath D, Tandle AT and Deo MG: Loss of p53 gene as a biomarker of high risk oral leukoplakia. Indian J Biochem Biophy 34:266-273, 1997. 13. Saranath D, Tandle AT, Teni TR, et al: p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India. Oral Oncol. 35:242-250, 1999. 14. Field JK, Spandidos DA and Stell PM: Overexpression of the p53 gene in head and neck cancer, linked with heavy smoking and drinking. Lancet 339:502-503, 1992. 15. Miyashita T, Krajewski S, Krajweska M, et al: Tumor suppressor p53 is a regulator of bcl2 and bax expression in vitro and in vivo. Oncogene 9:1799 –1805, 1994. 16. Wang Y, Szekely L, Okan J, Klien G et al: Wild type p53 triggered apoptosis is inhibited by bcl2 in v-myc induced T-cell lymphoma lines. Oncogene 8:3427-3431, 1993. 17. Pollina L, Pacini F, Fontanini G et al: Bcl2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas. Br J Cancer 73:139-143, 1996. 18. Qi-Lung, Abel P, Foster CB, et al: Bcl-2: Role in epithelial differentiation and oncogenesis. Human Pathol. 27:102-109, 1996. 19. Jordan RCK, Catzavelos GC, Barrett AW, et al: Differential expression of bcl2 and bax in squamous cell carcinomas of the oral cavity. Oral Oncol. 32B:394-400, 1996. 20. Stoll C, Baretton G, Abrens C, et al: Prognostic significance of apoptosis and associated factors in oral squamous cell carcinoma. Virchows Arch 436:102-108, 2000. 21. Birchall MA, Schock E, Harmon BV et al : Apoptosis, Mitosis, PCNA and bcl2 in normal, leukoplakic and malignant epithelia of the human oral cavity: prospective, in-vivo study. Oral Oncol 3:419-425, 1997. 22. Pena J, Thompson CB, Recant W, et al: Bcl-xL and Bcl2 expression in squamous cell carcinoma of head and neck. Cancer 85:164-170, 1999. 23. Yao L, Iwai M and Furuta I: Correlation of bcl2 and p53 expression with the clinico pathological features in tongue squamous cell carcinomas. Oral Oncol. 35:56-62, 1999. 24. Ravi D, Ramadas K, Mathew BS, et al : De novo programmed cell death in oral cancer. Histopathol. 14:241-249, 1999. 25. Kannan K, Lakshmi Latha PN and Shanmugan G : Expression of bcl2 oncoprotein in Indian oral squamous cell carcinomas. Oral Oncol 34:373-377, 1998. 26. McAlinden RL, Maxwell P, Napiet S, et al: Bcl-2 expression in sequential biopsies of potentially malignant oral mucosal lesions assessed by immunocytochemistry. Oral Diseases 6:318-326, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 109
EP 114
PG 6
ER
PT J
AU Nagy, G
Szekeres, Gy
Kvell, K
Berki, T
Nemeth, P
AF Nagy, Gergely
Szekeres, Gyorgy
Kvell, Krisztian
Berki, Timea
Nemeth, Peter
TI Development and Characterisation of a Monoclonal Antibody Family Against Aquaporin 1 (AQP1) and Aquaporin 4 (AQP4)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE aquaporin 1; aquaporin 4; anti-aquaporin antibodies; monoclonal antibody; immunohistochemistry
ID aquaporin 1; aquaporin 4; anti-aquaporin antibodies; monoclonal antibody; immunohistochemistry
AB Recent studies have discovered the existence of water-channel molecules, the so called aquaporins (AQP) presumably involved in active, ATP dependent water transport between the intracellular and extracellular compartments. Both genetic and protein sequences and structures of the AQPs are known and crystallographic analyses of some members of the AQP family have been performed. Specific antibodies are required to examine their histological locations and analyse their roles in physiological and pathological pathways of water transportation and osmotic regulation. Until recently some polyclonal antibodies have been developed against certain members of the AQP family. However, to date highly specific monoclonal antibodies against aquaporins do not exist. We have developed a monoclonal antibody family against the aquaporin 1 (AQP1) and aquaporin 4 (AQP4) molecules. Well-conserved epitop sequences of AQP1 and AQP4 proteins were selected by computer analysis and their synthetic peptide fragments were used as the antigens of immunisation and the following screening. Antibodies were characterised by immunoserological methods (ELISA, dot-blot and immunoblot), flow cytometry and immunohistochemistry of formaldehyde-fixed and paraffin-embedded tissue samples. RT-PCR tests controlled the specificity of the immune reactions. Our monoclonal antibodies recognised AQP1 and AQP4 in all the techniques mentioned above and apparently they are useful both in various quantitative and qualitative measurements of the expressions of AQP1 and AQP4 in several species (human, rat, mouse, invertebrates, even plants). According to preliminary immunohistochemical studies our monoclonal anti-AQP1 and anti-AQP4 antibodies are appropriate tools of patho-morphological examinations on routine formol-paraffin tissue samples.
C1 [Nagy, Gergely] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Szekeres, Gyorgy] Hisztopatologia KFTPecs, Hungary.
[Kvell, Krisztian] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Berki, Timea] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
RP Nemeth, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM peter.nemeth@aok.pte.hu
CR Agre, P, Brown D, Nielsen S: Aquaporin water channels: unanswered questions and unresolved controversies. Curr Op Cell Biol 7:472-483, 1995.
Agre, P, Preston GM, Smith BL, et al: Aquaporin CHIP: the arce type molecular water channel. Am J Physiol 265:463-476, 1993.
Bodis B, Nagy G, Nemeth P, et al: Ative water selective channels in the stomach: investigation of aquaporins after ethanol and capsaicin treatment in rats. J Phys Paris 95:271-278, in press).
Borgnia M, Nielsen S, Engel A et al: Cellular and molecular biology of the aquaporin water channels. Ann Rev Biochem 68:425-458, 1999.
Dyson, HJ, Wright PE: Antigenic peptides. FASEB J 9:37-42, 1995.
Endo M, Jain RK, Witwer B et al: Water channel, aquaporin 1, expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res 58:89-98, 1999.
Engel A: Structural analyses of the aquaporin super-family. Nephrol Dial Transplant. 15 Suppl. 6:23-5, 2000.
Fujita, Horio Y, Nielsen S, et al: High-resolution immunogold cytochemistry indicates that AQP4 is concentrated along the basal membrane of parietal cell in rat stomach. FEBS Lett 459:305-9, 1999.
Greisz V, Burghardt B, Ferguson CJ, et al: Expression of aquaporin 1, AQP1, water channels in human labial salivary glands. Arch Oral Biol 44:S53-57, 1999.
Greisz V, Kwon TH, Hurley PT, et al: Identification and localization of aquaporin water channels in human salivary glands. Am J Phys Gatrointest Liver Phys 281:G247-254, 2001.
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King LS, Yasui M, Agre P: Aquaporins in health and disease. Mol Med Today 6:60-5, 2000.
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Vizuete ML, Venero JL, Vargas C et al: Astrocytes and aquaporin- 4, AQP4, play a significant role in brain ion homeostasis. Neurobiol Dis 6:245-58, 1999.
Work, TS, Work E, editors. Laboratory techniques in Biochemistry and Molecular Biology, Vol. 11. Elsevier Science, Oxford. 37-41, 94-96, 1982.
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Zor T, Selinger Z: Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Anal Biochem 236: 302-308, 1996.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 115
EP 124
PG 10
ER
PT J
AU Madhavan, M
Srinivas, P
Abraham, E
Ahmed, I
Vijayalekshmi, RN
Balaram, P
AF Madhavan, Maya
Srinivas, Priya
Abraham, Elizabeth
Ahmed, Iqbal
Vijayalekshmi, Rugmini Narayana
Balaram, Prabha
TI Down Regulation of Endothelial Adhesion Molecules in Node Positive Breast Cancer: Possible Failure of Host Defence Mechanism
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VCAM; ICAM; E-selectin; invasion; breast cancer
ID VCAM; ICAM; E-selectin; invasion; breast cancer
AB Endothelial cell adhesion molecules (CAMs) are important in tumorigenesis and host defense mechanism. Their status in breast cancer with regard to nodal invasion is not yet known. Hence we looked at the expression of three important CAMs: VCAM, ICAM and E-selectin. A downregulation of all these CAMs was noted in node positive breast cancer in comparison to node negative cases. This suggests shedding of these molecules in cases with nodal metastasis which might help the tumor cells to escape the host defense mechanism. On multi-variate analysis, VCAM alone emerged as an independent predictor of nodal metastasis.
C1 [Madhavan, Maya] Regional Cancer Centre, Division of Cancer Research, 695011 Trivandrum, Kerala, India.
[Srinivas, Priya] Regional Cancer Centre, Division of Cancer Research, 695011 Trivandrum, Kerala, India.
[Abraham, Elizabeth] Regional Cancer Centre, Division of HistopathologyTrivandrum, Kerala, India.
[Ahmed, Iqbal] Regional Cancer Centre, Division of Surgical OncologyTrivandrum, Kerala, India.
[Vijayalekshmi, Rugmini Narayana] University of Kerala, Department of BiochemistryTrivandrum, Kerala, India.
[Balaram, Prabha] Regional Cancer Centre, Division of Cancer Research, 695011 Trivandrum, Kerala, India.
CR Nicolson GL: Organ colonization and cell-surface properties of malignant cells. Biochim Biophys Acta 695:113-176, 1982.
Pauli BU, Augustin-Voss HG, El-Sabban ME, et al: Organ preference of metastasis. The role of endothelial cell adhesion molecules. Cancer Metastasis Review 9:175-189, 1990.
Nicolson GL: Metastatic tumor cell interaction with endothelium, basement membrane and tissue. Curr Opin Cell Biol 1:1009-1019, 1989.
Liotta LA: Tumor invasion and metastasis of the extracellular matrix. Cancer Res 46:1-7,1986.
Harning R, Mainolfi E, Brystryn JC, et al: Serum levels of circulating intercellular adhesion molecule 1 in human malignant melanoma Cancer Res 51:5003-5005, 1991.
Srivastava MD, Srivastava A, Srivastava BI: Soluble interleukin 2 receptor, soluble CD8 and soluble intercellualr adhesion molecule 1 levels in hematologic malignancies Leuk Lymphoma 12:241-251, 1994.
Koyama S, Ebihara T, Fukao K: Expression of intercellular adhesion molecule1, ICAM-1)during the development of invasion and/or metastasis of gastric carcinoma. J Cancer Res Clin Oncol 118:609-614, 1992.
Pober JS, Cotran RS: Immunologic interactions of T lymphocytes with vascular endothelium. Adv Immunol 50:261-302, 1991.
Stoolman LM: Adhesion molecules controlling lymphoctye migration. Cell 56:907-910, 1989.
Osborn L: Leukocyte adhesion to endothelium in inflammation. Cell 62:3-6, 1990.
Osborn L , Hession C, Tizard R, et al: Direct expression cloning of Vascular cell adhesion molecule-1, a cytokine induced endothelial protein that binds to lymphocytes. Cell 59:1203-1211,1989.
Vogetseder W, Feichtinger H, Schulz TF, et al: Expression of 7F7-antigen, a human adhesion molecule identical to Intercellular adhesion molecule-1, ICAM-1, in human carcinomas and their stromal fibroblasts. Int J Cancer 43:768-773,1989.
Makgoba MW, Sanders ME, Ginther Luce GE, et al: Functional evidence that intercellular adhesion molecule(ICAM-1, is a ligand for LFA-1 dependent adhesion in T-cell mediated cytotoxicity. Eur J Immunol 18:637-640, 1988.
Bevilacqua MP, Pober JS, Mendrick DL, et al: Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Nat Acad Sci, Wash, 84:9238-9242, 1987.
Lasky LA: Selectins: interpreters of cell specific carbohydrate information during inflammation. Science 258:964-969,1992.
Tsujisaki M, Imai K, Hirata H, et al: Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases. Clin Exp Immunol 85:3-8, 1991.
Viac J, Gueniche A, Faure M, et al: Soluble intercellular adhesion molecule 1(sICAM-1, and malignant melanoma. Cancer Letters 72:191-194, 1993.
Gruss HJ, Dolken G, Brach MA, et al: Serum levels of circulating ICAM-1 are increased in Hodgkins disease. Leukemia 7:1245-1249, 1993.
Wittig BM, Treichel U, Blaheta R, et al: Soluble E-selectin enhances ICAM-1 expression in human tumor cell lines. Exp Cell Res 237:364-70,1997.
Lawson C, Ainsworth M, Yacoub M, et al: Ligation of ICAM- 1 on endothelial cells leads to expression of VCAM-1 via a nuclear factor-KB independent mechanism. J Immunol 162:2990-6.1999.
Rothlein R, Mainolf EA, Czajkowski M, Marlin SD: A form of circulating ICAM-1 in human serum. J Immunol 147:3788- 3793, 1991.
Seth R, Raymond FD, Mukgoba MW: Cirulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Lancet 338:83-84, 1991.
Kageshita Y, Yoshii A, Kimura T, et al: Analysis of expression and soluble form of intercellular adhesion molecule-1 in malignant melanoma. J Dermatol 19:836-840, 1992.
Anastossiou G, Schilling H, Stang A, et al: Expression of the cell adhesion molecules ICAM-1, VCAM-1 and NCAM in uveal melanoma: A clinicopathological study. Oncology 58:83-88, 2000.
Pizzolo G, Vinante F, Nadali G, et al: ICAM-1 tissue overexpression associated with increased serum levels of its soluble form in Hodgkins disease. Br J Haematol 84:161-162, 1993.
Vogetseder W, Feichtinger H, Schulz TF, et al: Expression of 7F7 antigen, a human adhesion molecule identical to intercellular adhesion molecule-1, ICAM-1, in human carcinomas and their stromal fibroblasts. Int J Cancer 43:768-773, 1989.
Gearing AJH, Newman W: Circulating adhesion molecules in disease. Immunol Today 14:506-512, 1993.
Banks RE, Gearing AJH, Hemingway IK, et al: Circulating intercellular adhesion molecule-1, ICAM-1), E-selectin and vascular cell adhesion molecule-1(VCAM-1, in human malignancies. Br J Cancer 68:122-124, 1993.
Liu CM, Sheen TS, Ko JY, et al: Circulating intercellular adhesionmolecule1( ICAM-1), E-selectin and vascular cell adhesion molecule1(VCAM-1, in head and neck cancer. Br J Cancer 79:360-362,1999.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 125
EP 128
PG 4
ER
PT J
AU Dekel, Y
Koren, R
Kugel, V
Livne, MP
Gal, R
AF Dekel, Yoram
Koren, Rumelia
Kugel, Valentina
Livne, M Pinhas
Gal, Rivka
TI Significance of Angiogenesis and Microvascular Invasion in Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; factor VIII; renal cell carcinoma; prognosis
ID angiogenesis; factor VIII; renal cell carcinoma; prognosis
AB The aim of this study is to evaluate the relationship between tumor angiogenesis and microvascular invasion, and the subsequent development of metastatic disease in patients undergoing surgery for renal cell carcinoma (RCC). The study group consisted of 102 patients who underwent surgery for RCC between the years 1990 and 1997 in our institute with a mean follow up period of 81.3 months. Paraffin blocks were stained for Factor VIII - related antigen and CD34 which decorate endothelial cells in order to assess angiogenesis and microvascular invasion and their relevance for developing metastatic disease. When Factor VIII- related antigen staining was used we found that the microvessel count correlated with the development of metastatic disease with a mean count of 49.7 for patients with no evidence of disease and a mean count of 95.5 for patients who developed metastatic disease (p<0.05). We also found that microvascular invasion correlated with the development of metastatic disease. It was demonstrated in 55.5% of patients who developed metastatic disease versus 23.8% of patients with no evidence of disease with Factor VIII staining (p<0.05), and in 33.3% and 7.1%, respectively (p<0.05) with CD34 staining. This study suggest that demonstration of intense angiogenesis and micro-vascular invasion may be a predictor of a more aggressive tumor mandating closer follow up and consideration of adjuvant therapy.
C1 [Dekel, Yoram] Hasharon Hospital, Department of Urology, Rabin Medical Center, Campus Golda, Petah Tikva, and Sackler Faculty of MedicinePetach Tikvah, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Kugel, Valentina] Hasharon Hospital, Department of Urology, Rabin Medical Center, Campus Golda, Petah Tikva, and Sackler Faculty of MedicinePetach Tikvah, Israel.
[Livne, M Pinhas] Hasharon Hospital, Department of Urology, Rabin Medical Center, Campus Golda, Petah Tikva, and Sackler Faculty of MedicinePetach Tikvah, Israel.
[Gal, Rivka] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
RP Koren, R (reprint author), A, Rabin Medical Center (Golda Campus), Department of Pathology, Petach Tikvah, Israel.
EM rumelia@isdnmail.co.il
CR Bex A, Luboldt H, Sudermann T, et al: Influence of linomide on local tumor growth and metastasis of the human hormoneresistant prostate cancer cell line PC3 in an orthotopic model. Eur Urol 37:628-633, 2000.
Bochner BH, Cote RJ, Weidner N, et al: Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst 87:1603-1612, 1995.
Campbell SC: Advances in angiogenesis research: relevance to urological oncology. J Urol 158:1663-1674, 1997.
Crew JP: Vascular endothelial growth factor: An important angiogenic mediator in bladder cancer. Eur Urol 35:2-8, 1999.
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DeKernion JB, Mukamel E: Selection of initial therapy for renal cell carcinoma. Cancer 60:539-546, 1987.
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Guinan PD, Vogelzang NJ, Freman AM: Renal cell carcinoma: tumor size, stage and survival. J Urol 153:901-905, 1995.
Hatcher PA, Anderson EE, Paulson DF, et al: Surgical management and prognosis of renal cell carcinoma invading the vena cava. J Urol 145:20-25, 1991.
Hollingsworth HC, Kohn EC, Steinberg SM, et al: Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147:33-41, 1995.
Imazano Y, Takebayashi Y, Nishiyama K, et al: Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma. J Clin Oncol15:2570-2578, 1997.
Lang H, Lindner V, Saussine C, et al: Microscopic venous invasion: A prognostic factor in renal cell carcinoma. Eur Urol 38:600-605, 2000.
Maldazys JD, deKernion JB: Prognostic factors in metastatic renal carcinoma. J Urol 136:376-380, 1986.
Mancilla-Jimenez R: Papillary renal cell carcinoma: a clinical, radiologic and pathologic study of 34 cases. Cancer 38:246- 270, 1976.
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Yoshino S, Kato M, Okada K: Prognostic significance of microvessel count in low stage renal cell carcinoma. Int J Urol 2:156-160, 1995.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 129
EP 132
PG 4
ER
PT J
AU Arista-Nasr, J
Gutierrez-Villalobos, L
Nuncio, J
Maldonaldo, H
Bornstein-Quevedo, L
AF Arista-Nasr, Julian
Gutierrez-Villalobos, Lisa
Nuncio, Juan
Maldonaldo, Hector
Bornstein-Quevedo, Leticia
TI Fibrolamellar Hepatocellular Carcinoma in Mexican Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE fibrolamellar; hepatocellular carcinoma; liver; neoplasm
ID fibrolamellar; hepatocellular carcinoma; liver; neoplasm
AB The aim of this report is to describe the frequency, clinical, and morphologic characteristics of fibrolamellar hepatocellular carcinoma in Mexican patients. Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma. Although this tumor appears to be predominant among the Caucasian population of the U.S, FLHCC has been described in many other countries. The frequency and characteristics of FLHCC in Latin American population is almost unknown. The clinico-pathologic characteristics of seven (5.8%) Mexican patients with FLHCC, obtained among 121 hepato-cellular carcinomas are described. The frequency of these tumors was compared with the frequency reported in other geographic areas in the international literature between 1980 and 1999. There were four women and three men. Two patients had taken oral contraceptives for six months and a year prior to diagnosis; another patient had positive serology for the hepatitis B virus. Common symptoms included a palpable mass, abdominal pain and weight loss; two patients presented jaundice. In two patients the tumor had been removed eight and three years previously, and they were readmitted when FLHCC recurred. In three patients the diagnosis was suspected in radiological studies (computed tomography and/or magnetic resonance). Laboratory tests were non-specific. In four patients, resection of the tumor was performed, and in the remaining three the neoplasm was diagnosed by percutaneous hepatic biopsy. Two patients had died of disease at the time of the study, and another was alive with recurrent disease. Conclusions: fibrolamellar hepatocarcinoma is an uncommon, but not an exceptional neoplasm in our population and represents 5.8% of all hepatocarcinomas reviewed.
C1 [Arista-Nasr, Julian] Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15 Coi. Seccion XVI, 14000 Mexico City, Mexico.
[Gutierrez-Villalobos, Lisa] Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15 Coi. Seccion XVI, 14000 Mexico City, Mexico.
[Nuncio, Juan] Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15 Coi. Seccion XVI, 14000 Mexico City, Mexico.
[Maldonaldo, Hector] Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15 Coi. Seccion XVI, 14000 Mexico City, Mexico.
[Bornstein-Quevedo, Leticia] Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15 Coi. Seccion XVI, 14000 Mexico City, Mexico.
RP Arista-Nasr, J (reprint author), Instituto National de Ciencias Medicas y Nutricion, Salvador Zubiran, Department of Pathology, 14000 Mexico City, Mexico.
EM pipa5@hotmail.com
CR Saab S, Yao F: Fibrolamellar hepatocellular carcinoma. Case reports and a review of the literature. Dig Dis Sci 41:1981- 1985, 1996.
Ruffin MT: Fibrolamellar hepatoma. Am J Gastroenterol 85: 577-581, 1990.
Teilez-Zenteno JF, Hernandez-Ronquillo L, Tapia-Rangel B, et al. Hepatocarcinoma variedad fibrolamelar en una joven de 17 anos de edad. Gac Med Mex 135: 83-87, 1999.
Chedid A, Ryan LM, Dayal Y, et al: Morphology and other prognostic factors of hepatocellular carcinoma. Arch Pathol Lab Med 123:524-8, 1999.
Wood WJ, Raelings M, Evans H, et al: Hepatocellular carcinoma: importance of histologic classification as a prognostic factor. Am J Surg 155: 663-666, 1988.
Yoshida K, Amemiya A, Kobayashi S, et al. Fibrolamellar carcinoma of the liver in the Orient. J Surg Oncol 39: 187-189, 1988.
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Eckstein RP, Bambach CP; Stiel D, et al: Fibrolamellar carcinoma as a cause of bile duct obstruction. Pathology 20:326-31, 1988.
Azais-Nobunski B; Dahan D, Tubiana JM: Fibrolamellar carcinoma of the liver. Apropos of 2 cases. Review of the literature. Ann Radiol, Paris, 30:395-399, 1897.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 133
EP 137
PG 5
ER
PT J
AU Demokan, S
Muslumanoglu, M
Yazici, H
Igci, A
Dalay, N
AF Demokan, Semra
Muslumanoglu, Mahmut
Yazici, Hulya
Igci, Abdullah
Dalay, Nejat
TI Investigation of Microsatellite Instability in Turkish Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microsatellite instability; breast cancer
ID microsatellite instability; breast cancer
AB Multiple somatic and inherited genetic changes that lead to loss of growth control may contribute to the development of breast cancer. Microsatellites are tandem repeats of simple sequences that occur abundantly and at random throughout most eucaryotic genomes. Microsatellite instability (MI), characterized by the presence of random contractions or expansions in the length of simple sequence repeats or microsatellites, is observed in a variety of tumors. The aim of this study was to compare tumor DNA fingerprints with constitutional DNA fingerprints to investigate changes specific to breast cancer and evaluate its correlation with clinical characteristics. Tumor and normal tissue samples of 38 patients with breast cancer were investigated by comparing PCR-amplified microsatellite sequences D2S443 and D21S1436. Microsatellite instability at D21S1436 and D2S443 was found in 5 (13%) and 7 (18%) patients, respectively. Two patients displayed instability at both marker loci. No association was found between MI and age, family history, lymph node involvement and other clinical parameters.
C1 [Demokan, Semra] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Muslumanoglu, Mahmut] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Yazici, Hulya] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
[Igci, Abdullah] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Dalay, Nejat] Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
RP Dalay, N (reprint author), Oncology Institute, Department of Basic Oncology, 34390 Capa-Istanbul, Turkey.
EM ndalay@yahoo.com
CR Dickson RB, Lippman ME. Molecular basis of breast cancer. In: The Molecular Basis of Cancer, WB Saunders, 358-384, 1995.
Hovig E, Smith-Sorensen B, Uitterlinden AG, et al: Detection of DNA variation in cancer. Pharmacogenetics 2:317-328, 1992.
Paulson TG, Wright FA, Parker BA, et al: Microsatellite instability correlates with reduced survival and poor disease prognosis in breast cancer. Cancer Res 56:4021-4026, 1996.
Ali S, Muller CR, Epplen JT. DNA fingerprinting by oligonucleotide probes specific for simple repeats. Hum Genet 74:239- 243, 1986.
Decker RA, Moore J, Ponder B, et al: Linkage mapping of human chromosome 10 microsatellite polymorphisms. Genomics 12:604-606, 1992.
Weber JL, Wong C. Mutation of human short tandem repeats. Hum Mol Genet 2:1123-1128, 1993.
Branch P, Aquilina G, Bignami M, et al: Defective mismatch binding and a mutator phenotype in cells tolerant to DNA damage. Nature 362:652-654, 1993.
Fey MF, Wells RA, Wainscoat JS, et al: Assessment of clonality in gastrointestinal cancer by DNA fingerprinting. J Clin Invest 82:1532-1537, 1988.
Jeffreys AJ, Neumann R, Wilson V. Repeat unit sequence variation in minisatellites: A novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60:473-485, 1990.
Samowitz WS, Curtin K, Ma KN, et al: Microsatellite instability in sporadic colon cancre is associated with an improved prognosis at the population level. Cancer Epidem Biomarkers Prev 10:917-923, 2001.
van Rhijn BWG, Lurkin I, Kirkels WJ, et al: Microsatellite analysis – DNA test in urine competes with cystoscopy in follow- up of superficial bladder carcinoma. Cancer 92:768-775, 2001.
Han HJ, Yanagisawa A, Kato Y, et al: Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res 53:5087-5089, 1993.
Gonzalez R, Silva JM, Sanchez A, et al: Microsatellite alterations and TP53 mutations in plasma DNA of small cell lung cancer patients: Follow-up study and prognostic significance. Annals Oncol 11:1097-1104, 2000.
Contegiacomo A, Palmirotta R, De Marchis L, et al: Microsatellite instability and pathological aspects of breast cancer. Int J Cancer 64:264-268, 1995.
Vaurs-Barriere C, Penault-Llorca F, Laplace-Marieze V, et al: Low frequency of microsatellite instability in BRCA1 mutated breast tumors. J Med Genet 37:1-3, 2000.
Chen P, Hurst T, Khoo SK. Detection of somatic DNA alterations in ovarian cancer by DNA fingerprint analysis. Cancer 67:1551-1555, 1991.
Fearon ER, Vogelstein B. Tumor suppressor and DNA repair gene defects in human cancer. In : Holland JF, Bast RC, Morton DL, Frei III E, Kufe DW, Weichselbaum RR, eds). Cancer Medicine. 4. ed. Williams and Wilkins, 97-119, 1997.
Alexander J, Watanabe T, Wu TT, et al: Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 158:527-535, 2001.
Seripa D, Parrella P, Gallucci M, et al: Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine. Int J Cancer 95:364-369, 2001.
Rha SH, Dong SM, Jen J, et al: Molecular detection of cervical intraepithelial neoplasia and cervical carcinoma by microsatellite analysis of Papanicolaou smears. Int J Cancer 93:424-429, 2001.
Gonzalez-Zulueta M, Ruppert JM, et al: Microsatellite instability in bladder cancer. Cancer Res 53:5620-5623, 1993.
Sourvinos G, Kiaris H, Tsikkinis A, et al: Microsatellite instability and loss of heterozygosity in primary breast tumors. Tumor Biol 18:157-166, 1997.
Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 260:816-819, 1993.
Rush EB, Calvano JE, Van Zee KJ, et al: Microsatellite instability in breast cancer. Ann Surg Oncol 4:310-315, 1997.
Shaw JA, Walsh T, Chappell SA, et al: Microsatellite instability in early sporadic breast cancer. Br J Cancer 73:1393-1397, 1996.
Kasami M, Vnencak-Jones CL, Manning S, et al: Loss of heterozygosity and microsatellite instability in breast hyperplasia. Am J Pathol 150:1925-1931, 1997.
Krajinovic M, Richer C, Gorska-Flipot I, et al: Genomic loci susceptible to replication errors in cancer cells. Br J Cancer 78:981-985, 1998.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 138
EP 141
PG 4
ER
PT J
AU Cserni, G
Kovacs, RB
Tarjan, M
Sapi, Z
Domjan, Zs
Szabo, Z
AF Cserni, Gabor
Kovacs, Rita Beata
Tarjan, Miklos
Sapi, Zoltan
Domjan, Zsolt
Szabo, Zoltan
TI Sarcomatoid Renal Cell Carcinoma with Foci of Chromophobe Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE chromophobe renal cell carcinoma; sarcomatoid renal carcinoma; DNA-ploidy; p53
ID chromophobe renal cell carcinoma; sarcomatoid renal carcinoma; DNA-ploidy; p53
AB Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
[Kovacs, Rita Beata] St John's Hospital, Department of PathologyBudapest, Hungary.
[Tarjan, Miklos] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
[Sapi, Zoltan] St John's Hospital, Department of PathologyBudapest, Hungary.
[Domjan, Zsolt] Bacs-Kiskun County Teaching Hospital, Department of UrologyKecskemet, Hungary.
[Szabo, Zoltan] Bacs-Kiskun County Teaching Hospital, Department of UrologyKecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.c3.hu
CR Akhtar M, Kardar M, Linjawi T, et al: Chromophobe cell carcinoma of the kidney: a clinicopathologic study of 21 cases. Am J Surg Pathol 19:1245-1256, 1995.
Akhtar M, Kfoury H, Kardar A, et al: Sarcomatoid chromophobe cell carcinoma of the kidney. J Urol Pathol 4:155-166, 1996.
Akhtar M, Tulbah A, Kardar AH, Ali MA: Sarcomatoid renal carcinoma: the chromophobe connection. Am J Surg Pathol 21:1188-1195, 1997.
Bertoni F, Ferri C, Benati A, et al: Sarcomatoid carcinoma of the kidney. J Urol 137:25-28, 1987.
Crotty TB, Farrow GM, Liber MM: Chromophobe cell renal carcinoma, clinicopathological features of 50 cases. J Urol 154:964-967, 1995.
Gomez-Roman JJ, Mayorga-Fernandez M, Mayorga-Fernendez F, Val-Bernal JF: Sarcomatoid chromophobe cell renal carcinoma: immunohistochemical and lectin study in one case. Gen Diagn Pathol 143:63-69, 1997.
Hirokawa M, Shimizu M, Sakurai T, et al: Sarcomatoid renal carcinoma with chromophobe cell foci. Report of a case. APMIS 106:993-996, 1998.
Kovacs G: Molecular differential pathology of renal cell tumors Histopathology 22:1-8, 1993.
Kuroda N, Hayashi Y, Itoh H: A case of chromophobe renal cell carcinoma with sarcomatoid foci and a small daughter lesion. Pathol Int 48:812-817, 1998.
Mai KT, Veinot JP, Collins JP: Sarcomatous transformation of chromophobe cell renal carcinoma. Histopathology 34:557- 559, 1999.
Murphy WM, Beckwith JB, Farrow GM: Atlas of tumor pathology. Tumors of the kidney, bladder, and related structures. Third series. Armed Forces Institute of Pathology, Washington, 1994.
Renshaw AA, Henske EP, Loughlin KR, et al: Aggressive variants of chromophobe renal cell carcinoma. Cancer 78:1756- 1761, 1996.
Ro JY, Ayala AG, Sella A, et al: Sarcomatoid renal cell carcinoma: clinicopathologic study of 42 cases. Cancer 59:516-526, 1987.
Tardio JC: Chromophobe cell renal carcinomas with sarcomatoid areas: Histopathology 35:184-185, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 142
EP 144
PG 3
ER
PT J
AU Kabukcuoglu, F
Baksu, A
Yilmaz, B
Aktumen, A
Evren, I
AF Kabukcuoglu, Fevziye
Baksu, Alparslan
Yilmaz, Banu
Aktumen, Alpay
Evren, Ismail
TI Malignant Struma Ovarii
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Ovary; malignant struma ovarii; germ cell tumor
ID Ovary; malignant struma ovarii; germ cell tumor
AB Malignant struma ovarii is a rare form of ovarian germ cell tumors. Because of its rarity, diagnosis and management of the tumor has not been clearly defined. A 52-year-old female with follicular variant of papillary carcinoma arising in struma ovarii is presented. There was no evidence of clinical malignancy or metastases. However on the basis of histopathologic findings, the case was diagnosed as malignant struma ovarii. It was accepted as stage Ia tumor and no other treatment was considered after radical excision. Due to its fairly good prognosis, surgical excision has been the preferred treatment for those who do not have disseminated disease. Nevertheless, long-term follow-up is necessary to determine the course of the disease.
C1 [Kabukcuoglu, Fevziye] Etfal Training and Research Hospital, Pathology Department, M. Ismail Hakki sk No: 10/1 Dogancilar, 81160 Uskudar, Istanbul, Turkey.
[Baksu, Alparslan] Etfal Training and Research Hospital, Pathology Department, M. Ismail Hakki sk No: 10/1 Dogancilar, 81160 Uskudar, Istanbul, Turkey.
[Yilmaz, Banu] Etfal Training and Research Hospital, Pathology Department, M. Ismail Hakki sk No: 10/1 Dogancilar, 81160 Uskudar, Istanbul, Turkey.
[Aktumen, Alpay] Etfal Training and Research Hospital, Pathology Department, M. Ismail Hakki sk No: 10/1 Dogancilar, 81160 Uskudar, Istanbul, Turkey.
[Evren, Ismail] Etfal Training and Research Hospital, Pathology Department, M. Ismail Hakki sk No: 10/1 Dogancilar, 81160 Uskudar, Istanbul, Turkey.
RP Kabukcuoglu, F (reprint author), Etfal Training and Research Hospital, Pathology Department, 81160 Uskudar, Istanbul, Turkey.
EM etfaly@superonline.com
CR Ayhan A, Yany k F, Tuncer R, et al:Struma ovarii. Int J Gynecol Obstet 42:143-146, 1993.
Berghella V, Ngadiman S, Rosenberg H, et al: Malignant struma ovarii. A case report and review of the literature. Gynecol Obstet Invest 43:68-72; 1997.
Dardik RB, Dardik M, Westra W, Montz FJ: Malignant struma ovarii: Two case reports and a review of the literature. Gynecol Oncol 73:447-451, 1999.
Devaney K, Snyder R, Norris HJ, Tavassoli FA: Proliferative and histologically malignant struma ovarii: a clinicopathologic study of 54 cases. Int J Gynecol Pathol 12:333-343, 1993.
Gonzales A, Kaufman RH, Braungardt CD, et al: Adenocarcinoma of thyroid arising in struma ovarii, malignant struma ovarii). Report of two cases and review of the literature. Obstet Gynecol 21:567-576, 1963.
Karseladze AI, Kulinitch SI: Peritoneal strumosis. Path Res Pract 190:1082-1085, 1994.
Nogales FF: Germ cell tumours of the ovary, In: Obstetrical and Gynecological Pathology., Eds: Fox H and Wells M): 4th ed, Churchill Livingstone, New York, 1995, pp 847-896.
O’Connell MEA, Fisher C, Harmer CL: Malignant struma ovarii: presentation and management. Br J Radiol 63:360-363, 1990.
Pardo-Mindan FJ, Vazquez JJ: Malignant struma ovarii Light and electron microscopic study. Cancer 51:337-343, 1983.
Rose PG, Arafah B, Abdul-Karim FW: Malignant struma ovarii: recurrence and response to treatment monitored by thyroglobulin levels. Gynecol Oncol 70:425-427, 1998.
Szyfelbein WM, Young RH, Scully RE:Struma ovarii simulating ovarian tumors of other types. A report of 30 cases. Am J Surg Pathol 19(1): 21-29, 1995.
Talerman A: Germ cell tumors of the ovary: In Blaustein’s Pathology of the Female Genital Tract., Ed: Kurman RJ), 4th ed, Springer-Verlag, New York 1994, pp 849-914.
Thomas RD, Batty VB: Metastatic malignant struma ovarii. Two case reports. Clin Nucl Med 17:577-578.
Vadmal MS, Smilari TF, Lovecchio JL, et al: Diagnosis and treatment of disseminated struma ovarii with malignant transformation. Gynecol Oncol 64:541-546, 1997.
Willemse PHB, Oosterhuis JW, Aalders JG, et al: Malignant struma ovarii treated by ovariectomy, thyroidectomy, and 131I administration. Cancer 60:178-182, 1987.
Woodruff JD, Rauh T, Markley RL: Ovarian struma. Obstet Gynecol 27:194-201, 1966.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 145
EP 147
PG 3
ER
PT J
AU Agarwal, N
Shatma, CM
Deol, P
Mehta, SV
Sarkar, Ch
AF Agarwal, M. Nitesh
Shatma, C M
Deol, S. Parminder
Mehta, Singh Veer
Sarkar, Chitra
TI Epithelioid Sarcoma of the Sciatic Nerve Perineural Sheath: a Mimic of Nerve Sheath Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE epithelioid sarcoma; sciatic nerve; soft tissue tumor; sarcoma
ID epithelioid sarcoma; sciatic nerve; soft tissue tumor; sarcoma
AB We report herein a rare case of epithelioid sarcoma, in a 39-year old lady involving the sciatic nerve. Clinically and radiologically it stimulated a nerve sheath tumor. Involvement of a nerve by an epithelioid sarcoma is extremely uncommon. To the best of our knowledge, this is the first case of an epithelioid sarcoma involving the sciatic nerve and needs documentation.
C1 [Agarwal, M. Nitesh] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Shatma, C M] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Deol, S. Parminder] All India Institute of Medical Sciences, Department of NeuroradiologyNew Delhi, India.
[Mehta, Singh Veer] All India Institute of Medical Sciences, Department of NeurosurgeryNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sarkarcs@hotmail.com
CR Enzinger FM: Epithelioid sarcoma. A sarcoma simulating a granuloma or a carcinoma. Cancer 26:1029-1041, 1970.
Laskowski J: Sarcoma aponeuroticum. Nowotwary 11: 61-67, 1961.
Enzinger FM, Weiss SW: Soft tissue tumors, 3rd Ed. Mosby, St. Louis, Baltimore, New York pp 1074-1083; 1995.
Prat J, Woodruff JM, Matcove RC: Epithelioid sarcoma: An analysis of 22 cases indicating the prognostic significance of vascular invasion and regional lymph node metastasis. Cancer 41:1472-1487, 1978.
Chase DR, Enzinger FM: Epithelioid sarcoma: Diagnosis, prognostic indicators and treatment. Am J Surg Pathol 9:241- 263, 1985.
Bos GD, Pritchard DJ, Reiman HM, et al: Epithelioid sarcoma. An analysis of fifty-one cases. J Bone Joint Surg 70:862-874, 1988.
Halling AC, Wollen PC, Pritchard DJ: Epithelioid sarcoma. A clinicopathological review of 55 cases. Mayo Clin Proc 71:636-642, 1996.
Bryan RS, Soule EH, Dobyns JH, et al: Primary epithelioid sarcoma of the hand and forearm. A review of thirteen cases. J Bone Joint Surg 56:458-465, 1974
Brennan MF. Soft tissue sarcoma involving the sciatic nerve. Brit J Surg 87:993, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 148
EP 150
PG 3
ER
PT J
AU Kaya, H
Aribal, E
Yegen, C
AF Kaya, Handan
Aribal, Erkin
Yegen, Cumhur
TI Apocrine Differentiation in Invasive Pleomorphic Lobular Carcinoma with In Situ Ductal and Lobular Apocrine Carcinoma: Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE lobular carcinoma; pleomorphic lobular carcinoma; apocrine differentiation
ID lobular carcinoma; pleomorphic lobular carcinoma; apocrine differentiation
AB Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). We report one case of PLC with in situ PLC and ductal carcinoma in situ with apocrine features.
C1 [Kaya, Handan] Marmara University, School of Medicine, Department of Pathology, Altunizade, 81190 Istanbul, Turkey.
[Aribal, Erkin] Marmara University Hospital, Department of RadiologyIstanbul, Turkey.
[Yegen, Cumhur] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
RP Kaya, H (reprint author), Marmara University, School of Medicine, Department of Pathology, 81190 Istanbul, Turkey.
EM hkaya@superonline.com
CR Damiani S, Dina R, Eusebi V: Eosinophilic and granular cell tumors of the breast. Semin Diag Pathol 16:117-125, 1999.
Eusebi V, Magalhaes F, Azzopardi JG: Pleomorphic lobular carcinoma of the breast: An aggressive tumor showing apocrine differentiation. Hum Pathol 23:655-662, 1992.
Losi L, Lorenzini P, Bussolati G: Apocrine differentiation in invasive carcinomas of the breast. Comparison of monoclonal and polyclonal gross cystic disese fluid protein 15 with prolactin inducible protein in RNA gene expression. Appl Immunohistochem 3:91-98, 1995.
Middleton LP, Palacios DM, Bryant BR, et al: Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol 24:650-1656, 2000.
Radhi JM: Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR. Histopath 36:156-160, 2000.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD AUG
PY 2002
VL 8
IS 2
BP 151
EP 152
PG 2
ER
PT J
AU Pisch, J
Moskovitz, T
Esik, O
Homel, P
Keller, S
AF Pisch, Julianna
Moskovitz, Tibor
Esik, Olga
Homel, Peter
Keller, Steven
TI Concurrent Paclitaxel-Cisplatin and Twice-a-DayIrradiation in Stage IIIA and IIIB NSCLC Shows Improvement in Local Control and Survival with Acceptable Hematologic Toxicity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB Non-small-cell lung cancer (NSCLC) has one of the highest death rates among the various forms of cancer. In attempts to improve on this unsatisfactory outcome, different radiation schedules and chemo-therapy agents have been examined in phase II or III studies. These have led to modest improvements in local control and survival, but combined therapies are associated with substantial hematologic toxicity. In this phase II study, 80 consecutive stage IIIA or IIIB NSCLC patients were treated with concomitant chemotherapy and twice-a-day irradiation in a total dose of 60 Gy in 1.5 Gy fractions. Patients scheduled for surgery received 45 Gy only. Paclitaxel (30 mg/m 2 ) on days 1-4 and cisplatin (100 mg/m 2 ) on day 5 were administered in the first and fourth weeks of treatment. Granulocyte colony stimulating factor (30 ng/m 2 ) was given on days 10-15. The local control, the 1- and 2-year survival rates and the occurrence of acute hematologic toxicity in the non-surgically treated patients were examined. Fifty-two patients were treated without and 28 with surgery. Among the non-surgically treated cases, 43 were evaluable for response and 47 for acute toxicity during a median follow-up of 22 months. The rate of local control was 65% (28/43), and the 1- and 2-year survival rates proved to be 68% and 48%, respectively, with a median survival of 28 months. Severe acute grade 3-4 toxicities included grade 4 leukopenia in 6 cases (13%), grade 3 leukopenia in 4 cases (9%), grade 3 esophagitis in 3 cases (6%) and grade 3 anemia in 3 cases (6%). Our results and the relevant data from the literature support the application of twice-a-day irradiation with concomitant chemotherapy in stage IIIA and IIIB NSCLC. Local control and survival were improved relative to once-a-day irradiation with sequential or concomitant chemotherapy.
C1 [Pisch, Julianna] Beth Israel Medical Center, Department of Radiation Oncology, First Avenue at 16 Street, NY 10003 New York, USA.
[Moskovitz, Tibor] Beth Israel Medical Center, Department of Medical OncologyNew York, USA.
[Esik, Olga] Beth Israel Medical Center, Department of BiostatisticsNew York, USA.
[Homel, Peter] Semmelweis University, Department of OncologyBudapest, Hungary.
[Keller, Steven] Montefiore Medical Center, Albert Einstein College of Medicine, Department of Thoracic SurgeryNew York, USA.
RP Pisch, J (reprint author), Beth Israel Medical Center, Department of Radiation Oncology, NY 10003 New York, USA.
EM JPisch@bethisraelny.org
CR Arriagada R, Le Chevalier T, Quoix E, et al: ASTRO Plenary: Effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. GETCB, Groupe d’Etude et Traitment des Cancers Bronchiques), FNCLC, Federation Nationale des Centres de Lutte contre le Cancer, and the CEBI trialists. Int J Radiat Oncol Biol Phys 20:1183-1190, 1991
Byhardt RW, Pajak TF, Emami B, et al: A phase I/II study to evaluate accelerated fractionation via concomitant boost for squamous, adeno, and large cell carcinoma of the lung: report of Radiation Therapy Oncology Group 84-07. Int J Radiat Oncol Biol Phys 26:459-468, 1993
Byhardt RW, Scott CB, Ettinger DS, et al: Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15. Cancer 75:2337-2344, 1995
Cancer Therapy Evaluation Program. Common Toxicity Criteria, Version 2.0., 1997, http://ctep.info.nih.gov
Choy H, Devore RF III, Hande KR, et al: A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer, a Vanderbilt Cancer Center Affiliate Network Study). Int J Radiat Oncol Biol Phys 47:931-937, 2000
Clamon G, Herndon J, Cooper R, et al: Radiosensitization with carboplatin for patients with unresectable stage III nonsmall- cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol 17: 4-11, 1999
Cox JD, Azarnia N, Byhardt RW, et al: A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with Radiation Therapy Oncology Group stage III non-small-cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11. J Clin Oncol 8:1543-55, 1990
Cox JD, Azarnia N, Byhardt RW, et al: Altered fractionation for non-small-cell carcinoma of the lung. Chest 96:68S-69S, 1999
Dillman RO, Seagren SL, Propert KJ, et al: A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 323: 940-945, 1990
Greenlee R, Hill-Harmon MB, Murray T, Thun M: Cancer statistics, 2001. CA Cancer J Clin 51:15-36, 2001
Hazuka MB, Crowley JJ, Bunn PA Jr, et al: Daily low—dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group Study. J Clin Oncol 12:1814-1820, 1994
International Commission on Radiation Units and Measurements. ICRU Report 50. Prescribing, recording, and reporting photon beam therapy. Bethesda, MD, 1993
International Commission on Radiation Units and Measurements, eds: Wambersie A, Landberg T, ICRU Report 62. Prescribing, recording, and reporting photon beam therapy, Supplement to ICRU Report 50, Bethesda, MD, 1999
Jeremic B, Shibamoto Y, Acimovic L, et al:Hyperfractionated radiation therapy and concurrent low-dose, daily carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy in stage III non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 50: 19-25, 2001
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Ass 54: 457-481, 1958
Kelly K, Hazuka M, Pan Z, et al: A phase I study of daily carboplatin and simultaneous accelerated, hyperfractionated chest irradiation in patients with regionally inoperable nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 40:559- 567, 1998
Komaki R, Scott C, Ettinger D, et al: Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group, RTOG, 92-04. Int J Radiat Oncol Biol Phys 38:149-155, 1997
Langer CJ, Curran WJ, Keller SM, et al: Report of phase II trial of concurrent chemoradiotherapy with radical thoracic irradiation, 60 Gy), infusional fluorouracil, bolus cisplatin and etoposid for clinical stage IIIB and bulky IIIA non-small cell lung cancer. Int J Radiat Oncol Biol Phys 26: 469-478, 1993
Martel MK, Ten Haken RK, Hazuka MB, et al: Estimation of tumor control probability model parameters from 3D dose distributions of non-small cell lung cancer patients. Lung Cancer 24: 31-37, 1999
Mehta MP, Tannehill SP, Adak S, et al: Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593. J Clin Oncol 11: 3518-3523, 1998
Perez CA, Pajak TF, Rubin P, et al: Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group. Cancer 59: 1874-1881, 1987
Pisch J, Berson AM, Malamud S, et al: Chemoradiation in advanced nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 33: 183-188, 1995
Saunders M, Dische S, Barrett A, et al: Continuous hyperfractionated accelerated radiotherapy, CHART, versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicenter trial. CHART Steering Committee. Lancet 350:161-165, 1997
Sause WT, Scott C, Taylor S, et al: Phase II trial of combination chemotherapy and irradiation in non-small-cell lung cancer, Radiation Therapy Oncology Group 88-04. Am J Clin Oncol 15:163-167, 1992
Sause W, Kolesar P, Taylor S IV, et al: Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 117:358-364, 2000
Schaake-Koning C, van den Bogaert W, Dalesio O, et al: Effects of concomitant cisplatin and radiotherapy on inoperable nonsmall- cell lung cancer. N Engl J Med 326: 524-530, 1992
Trott KR, Kummermehr J. The time factor and repopulation in tumors and normal tissues. Semin Radiat Oncol 3: 115-125, 1993
Withers HR, Taylor JM, Maciejewski B: The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 27: 131-146, 1988
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 163
EP 169
PG 7
ER
PT J
AU Khoursheed, M
Mathew, Th
Makar, RR
Sonia, L
H, A
Asfar, S
Al-Sayer, MH
Dashti, H
Al-Bader, A
AF Khoursheed, Mousa
Mathew, C. Thazhumpal
Makar, Ray Ragai
Sonia, L
H, Abul
Asfar, Sami
Al-Sayer, Musaed Hilal
Dashti, M. Hussain
Al-Bader, Abdullatif
TI Expression of CD44s in Human Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan binding proteins. Anti-body to CD44s is used to establish the association of its expression with the clinicopathological characteristics of colorectal cancer using immunohistochemical methods. The aim of this study is to investigate the expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as compared to adjacent normal colonic tissues. Furthermore, the level of expression of CD44s in colorectal cancer tissues was correlated with the degree of histological differentiation, Duke’s classification, sex, size and site of the tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin-fixed sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion, by the standard peroxidase-antiperoxidase method. Expression of these antigens were compared in normal and malignant epithelium and stromal cells. The results show that the level of CD44s in the epithelial and stromal cells was significantly higher in the colorectal cancer tissues than the normal ones. However, there was no association between the percentages of expressions of CD44s and the degree of histological differentiation, Duke’s classification, sex or size of the tumor. There was however, a significantly higher expression of CD44s in the epithelium of rectal cancer than that of colonic cancer. This study indicates that the expression of CD44s is significantly higher in colorectal cancer tissues. However, further studies are required to understand its role in tumor progression and metastasis of this disease.
C1 [Khoursheed, Mousa] Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
[Mathew, C. Thazhumpal] Kuwait University, Faculty of Medicine, Faculty of Allied Health SciencesSafat, Kuwait.
[Makar, Ray Ragai] Kuwait University, Faculty of Medicine, Department of PathologySafat, Kuwait.
[Sonia, L] Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
[H, Abul] Kuwait University, Faculty of Medicine, Faculty of Allied Health SciencesSafat, Kuwait.
[Asfar, Sami] Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
[Al-Sayer, Musaed Hilal] Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
[Dashti, M. Hussain] Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
[Al-Bader, Abdullatif] Kuwait University, Faculty of Medicine, Department of PathologySafat, Kuwait.
RP Khoursheed, M (reprint author), Kuwait University, Faculty of Medicine, Department of Surgery, 13110 Safat, Kuwait.
EM khoursheed@hsc.kuniv.edu.kw
CR Hart I, Goode N, Wilson R: Molecular aspects of metastatic cascade. Biochem Biophys Acta 989: 65-84, 1989
Screaton GR, Bell MV, Jackson DG, et al: Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced axons. Proc Natl Acad Sci USA 89:12160-12164, 1992
Tolg C, Hofmann M, Herrlich P, Ponta H: Splicing choice from ten variant exons establishes CD44 variability. Nucleic Acids Res 21: 1225-1229, 1993
Sleeman J, Moll J , Sherman L, et al. The role of CD44 splice variants in human metastatic cancer: Cell adhesion and human disease. Chichester, Ciba Foundation Symposium 189), Wiley, pp 142-56, 1995
Bartolazzi A, Jackson D, Bennett K, et al:Regulation of growth and dissemination of a human lymphoma by CD44 splice variants. J Cell Sci 108:1723-1733, 1995
Gunthert U, Hofmann M, Rudy W, et al: A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65: 13-24, 1991
Seiter S, Arch R, Reber S, et al: Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med 177: 443-455, 1993
Haynes B, Telen M, Hale L, Denning S: CD44-a molecule involved in leukocyte adherence and T-cell activation. Immunol Today 10: 423-428, 1989
Ropponen KM, Eskelinen MJ, Lipponen PK, et al: Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis. Scan J Gastroenterol 33: 301-309, 1998
Trowbridge I, Lesly J, Schulte R, et al: Biochemical characterization and cellular distribution of a polymorphic, murine cellsurface glycoprotein expressed in lymphoid tissues. Immunogenetics 15: 299-312, 1982
Herrlich P, Pals S, Ponta H: CD44 in colon cancer. Eur J Cancer 31:1110-1112, 1995
Boland CR, Kim YS: Transitional mucosa of the colon and tumor growth factors. Med Hypotheses 22: 237-243, 1987
Fox S, Fawcett J, Jackson DG: Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res 54:4539-4546, 1994
Hamilton PW, Watt PC, Allen DC: A morphometric assessment of transitional mucosa in the colon. Histopathology 13: 519- 530, 1988 151.Isaacson P, Attwood PR: Failure to demonstrate specificity of the morphological and histochemical changes in mucosa adjacent to colonic carcinoma, transitional mucosa). J Clin Pathol 32: 214-218, 1979 16. Sugino T, Gorham H, Yoshida K, et al. Progressive loss of CD44 gene expression in invasive bladder cancer. Am J Path 149:873-882, 1996 17. Wielenga VJM, Heider KH, Offerhaus GJA, et al. Expression of CD44 variant protein in human colorectal cancer is related to tumor progression. Cancer Res 53: 4754-756, 1993 18. Herrlich P, Zoller M, Pals ST, Ponta H. CD44 slice variants: Metastases meet lymphocytes. Immunol Today 14: 395-399, 1993 19. Tanabe KK, Ellis LM, Saya H:Expression of CD44RI adhesion molecule in colon carcinomas and metastases. Lancet 341:725- 726, 1993 20. East J, Hart IR: CD44 and its role in tumor progression and metastasis. Eur J Cancer 29A: 1921-1922, 1993 21. Mulder JW, Kruyt PM, Sewnath M, et al: Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet 344: 1470-1472, 1994 22. Koopman G, Heider KH, Horst E, et al. Activated human lymphocytes and aggressive non-Hodgkin’s lymphomas express a homologue of the rat metastasis-associated variant of CD44. J Exp Med 177: 897-904, 1993 23. Orzechowski HD, Beckenbach C, Herbst H, et al: Expression of CD44v6 is associated with cellular dysplasia in colorectal epithelial cells. Eur J Cancer 31A: 2073-2079, 1995 24. Mulder JW, Wielenga VJ, Polak MM, et al: Expression of mutant p53 protein and CD44 variant proteins in colorectal tumorigenesis. Gut 36:76-80 1995 25. Gotley DC, Fawcett J, Walsh MD, et al: Alternatively spliced variants of the cell adhesion molecule CD44 and tumor progression in colorectal cancer. Br J Cancer 74: 342-351, 1996 26. Abbasi AM, Forbes A, Chester KA, et al. Putatively metastatic specific CD44V6 is also expressed in normal colon and in human colorectal tumors. J Pathol 175(suppl): 137A, 1995 27. Imazeki F, Yokosuka O, Yamaguchi T, et al. Expression of variant CD44-massanger RNA in colorectal adenocarcinomas and adenomatous polyps in humans. Gastroenterology 110: 362- 368, 1996
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 170
EP 174
PG 5
ER
PT J
AU Elpek, G
Gelen, T
Karpuzoglu, G
Karpuzoglu, T
Aksoy, HN
Keles, N
AF Elpek, Ozlem Gulsum
Gelen, Tekinalp
Karpuzoglu, Gulten
Karpuzoglu, Tuncer
Aksoy, Hikmet Nazif
Keles, Nuran
TI Clinicopathologic Evaluation of CDw75 Antigen Expression in Colorectal Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB CDw75, a B lymphocyte surface antigen, is a sialylated carbohydrate epitope, which is generated by the enzyme b bgalactosyl a a2,6 sialyltransferase (Sia-T1). In colon carcinomas, although higher levels of Sia-T1 has been described and found to be correlated with metastatic potential of tumor cells, the expression of CDw75 antigen still remains unknown. To address this issue, we investigated immunohistochemically CDw75 antigen expression in 195 colorectal adenocarcinomas and their nodal metastases. The correlation between CDw75 antigen expression with selected clinicopathologic variables was analyzed by using Chi-square and Fisher’s exact tests. Positive staining was observed in 101 cases. Non-neoplastic mucosa was negative consistently. The frequency of positivity was decreased according to the degree of differentiation (p<0.001). Antigen expression was found to be associated with deeper penetration (p<0.006), positive lymph nodes (p<0.001), distant metastases (p<0.006) and advanced stage (p<0.001). Same relationships were detected in well and moderately differentiated tumors when CDw75 immunoreactivity was evaluated in each histologic grade separately. Our findings indicate that CDw75 antigen expression may be a good indicator of the biological aggressiveness of colorectal adenocarcinomas especially in tumors with well and moderately differentiated morphology.
C1 [Elpek, Ozlem Gulsum] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi, Typ Fakultesi, Patoloji ABD, Yeni Tip, Dekanlik,, 07070 Antalya, Turkey.
[Gelen, Tekinalp] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi, Typ Fakultesi, Patoloji ABD, Yeni Tip, Dekanlik,, 07070 Antalya, Turkey.
[Karpuzoglu, Gulten] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi, Typ Fakultesi, Patoloji ABD, Yeni Tip, Dekanlik,, 07070 Antalya, Turkey.
[Karpuzoglu, Tuncer] Akdeniz University, Medical School, Department of General SurgeryAntalya, Turkey.
[Aksoy, Hikmet Nazif] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi, Typ Fakultesi, Patoloji ABD, Yeni Tip, Dekanlik,, 07070 Antalya, Turkey.
[Keles, Nuran] Akdeniz University, Faculty of Medicine, Department of Pathology, Akdeniz Universitesi, Typ Fakultesi, Patoloji ABD, Yeni Tip, Dekanlik,, 07070 Antalya, Turkey.
RP Elpek, G (reprint author), Akdeniz University, Faculty of Medicine, Department of Pathology, 07070 Antalya, Turkey.
EM elpek@med.akdeniz.edu.tr
CR Bast BJEG, Zhou LJ, Freeman GJ: The HB-6, CDw75, and CD76 differentiation antigens are unique cell-surface carbohydrate determinants generated by the beta-galactoside alpha 2,6- sialyltransferase. J Cell Biol 116: 423-435, 1992
Bears OS, Henson DE, Hutter RVP: Manual for staging cancer. JB Lippincott Publ Co, Philadelphia, 1992
Cooper HS: Peanut lectin-binding sites in large bowel carcinoma. Lab Invest 47: 383-390, 1982
Dall’Olio F, Malagolini N, Di Stefano G: Increased CMPNeuAc: Gal1, 4GlcNac-R 2,6 sialyltranferase activity in human colorectal cancer tissues. Int J Cancer 44: 434-39, 1989
Dall’Olio F, Malagolini N and Di Stefano G: Post natal development of rat colon epithelial cells is associated with changes in the expression of a1,4-N-Acetylgalactosaminyltransferase involved in the synthesis of Sda antigen and of a2,6 sialyltransferase towards N-acetyllactosamine. Biochem J 270:519- 524, 1990
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 175
EP 182
PG 8
ER
PT J
AU Banfalvi, T
Boldizsar, M
Gergye, M
Gilde, K
Kremmer, T
Otto, Sz
AF Banfalvi, Teodora
Boldizsar, Mariann
Gergye, Maria
Gilde, Katalin
Kremmer, Tibor
Otto, Szabolcs
TI Comparison of prognostic significance of serum 5-S-Cysteinyldopa, LDH and S-100B protein in Stage III-IV malignant melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB 5-S-cysteinyldopa is a precursor of pheomelanin. S-100B protein is a low molecular weight, acidic, calcium binding, cytoplasmatic protein. LDH was defined as the most important serum parameter in disseminated melanoma. The aim of the present study was to compare the prognostic values of serum 5-S-Cysteinyldopa, S-100B and LDH concentrations in Stage III-IV melanoma patients. Serum samples were taken from 179 Stage III-IV melanoma patients at diagnosis. Serum 5-S-CD concentrations were determined by HPLC, S-100B protein by immunoluminometric assay while LDH by UV kinetic method. The mean/median concentrations of LDH, S-100B protein and 5-S-CD in Stage III patients ranged around the normal level. In Stage IV, the markers ranked as S100B = 5-S-CD > LDH for sensitivity, S-100B > LDH > 5-S-CD for specificity and LDH = S100B = 5-S-CD for positive predictive value, respectively. Furthermore, mean marker concentrations of patients with progressive disease differed significantly from nonprogresssive cases (when staging categories have been disregarded). Survival analysis indicated, that the initially elevated LDH and S-100B level in Stage IV disease predicts comparably short survival. Results of our study suggest that these serum marker values correlate well with Stages and disease progression. In Stage IV melanoma, the markers had appropriate sensitivity, high specificity as well as important positive predictive value. Among the studied serum markers S-100B protein and LDH proved to be similarly reliable in respect to the clinical outcome.
C1 [Banfalvi, Teodora] National Institute of Oncology, Department of Dermatology, Rath Gyorgy u.7-9.Budapest, Hungary.
[Boldizsar, Mariann] National Institute of Oncology, Department of BiochemistryBudapest, Hungary.
[Gergye, Maria] National Institute of Oncology, Central Clinical LaboratoryBudapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Department of Dermatology, Rath Gyorgy u.7-9.Budapest, Hungary.
[Kremmer, Tibor] National Institute of Oncology, Department of BiochemistryBudapest, Hungary.
[Otto, Szabolcs] National Institute of Oncology, Central Clinical LaboratoryBudapest, Hungary.
RP Banfalvi, T (reprint author), National Institute of Oncology, Department of Dermatology, Budapest, Hungary.
EM banfalvit@freemail.hu
CR Balch CM, Buzaid AC, Atkins MB, et al:A new American Joint Committee on cancer staging system cutaneous melanoma. Cancer 88: 1484-1491, 2000
Banfalvi T, Gilde K, Boldizsar M, et al: Serum levels of S-100 protein and 5-S-cysteinyldopa as markers of melanoma progression. Pathol Oncol Res 5: 218-223, 1999
Banfalvi T, Gilde K, Boldizsar M, et al: Serum concentration of 5-S-cysteinyldopa in patients with melanoma. Eur J Clin Invest 30: 900-904, 2000
Benathan M, Labidi F: Modulation of 5-S-cysteinyldopa formation by tyrosinase activity and intracellular thiols in human melanoma cells. Melanoma Res 6: 183-189, 1996
Berking C, Schlupen E, Schrader A, et al: Tumor markers in peripheral blood of patients with malignant melanoma: Multimarker RT-PCR versus a luminometric assay for S-100. Arch Dermatol Res 291: 479-484, 1999
Buer J, Probst M, Franzke A et al: Elevated serum levels of S- 100 and survival in metastatic malignant melanoma. Br J Cancer 75: 1373-1376, 1997
Buzaid AC, Ross MI, Balch CM, et al: Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of new staging system. J Clin Oncol 15: 1039-1051, 1997
Clark WH Jr, From L, Bernardino EA, Mihm MC: The histogenesis and biologic behaviour of primary human malignant melanomas of the skin. Cancer Res 29: 705-726, 1991
Deichmann M, Benner A, Bock Mjackel A, et al: S-100 beta, melanoma inhibiting activity and lactate dehydrogenase discriminate progressive from nonprogressive AJCC Stage IV melanoma. J Clin Oncol 17: 1891-1896, 1999
Deichmann M, Benner A, Kuner N et al: Are responses to therapy of metastatized melanoma reflected by decreasing serum values of S-100 beta or MIA? Melanoma Res. 11: 291-296, 2001
Djukanovic D, Hofmann U, Sucker A, et al: Comparison of S- 100 protein and MIA protein as serum markers in malignant melanoma. Anticancer Res 20: 2203-2207, 2000
Franzke A, Probst-kepper M, Buer J, et al: Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma. Br J Cancer 78: 40-45, 1998
Guo HB, Stoffel-Wagner B, Bierwirth T, et al: Clinical significance of serum S-100 in metastatic malignant melanoma. Eur J Cancer 31A: 1898-1902, 1995 140.Hansson C, Edholm L, Agrup G, et al: The quantitative determination of 5-S-cysteinyl-dopa and dopa in normal serum and in serum from patients with malignant melanoma by means of high performance liquid chromatography. Clin Chim Acta 88: 419-421, 1978 15. Hasegawa M, Takata M, Hatta N, Wakamatsu K, et al: Simultaneous measurement of serum 5-S-cysteinyldopa, circulating intercellular adhesion molecule-1 and soluble interleukin-2 receptor levels in Japanese patients with malignant melanoma. Melanoma Res 7: 243-251, 1997 16. Hauschild A: The use of serological tumor markers for malignant melanoma. Onkologie 20: 462-465, 1997 17. Hauschild A, Michaelsen J, Brenner W, et al: Prognostic significance of serum S-100B detection compared to routin blood parameters in advanced metastatic melanoma patients. Melanoma Res 9: 155-161, 1999 18. Horikoshi T, Ito Sh, Wakamatsu K, et al: Evaluation of melaninrelated metabolites as markers of melanoma progression. Cancer 73: 629-636, 1994. 19. Karnell R, von Schoultz E, Hansson LO, et al.: S 100 B protein, 5-S-cysteinyldopa and 6-hydroxy-5-metoxyindole-2-carboxylic acid as biochemical markers for survival prognosis in patients with malignant melanoma. Melanoma Res 7: 393-399, 1997 20. Karnell R, Kagedal B., Lindholm C, et al: The value of cysteinyldopa in the follow up of disseminated malignant melanoma. Melanoma Res 10: 363-369, 2000 21. Krahn G, Kaskel P, Sander S, et al: S-100 beta is a more reliable tumor marker in peripherial blood of patients with newly occurred melanoma metastases comparing to MIA, albumin and lactat dehydrogenase. Anticancer Res 21: 311-1316, 2001 22. Martenson ED, Hansson LO, Nilsson B, et al.: Serum S-100b protein as prognostic marker in malignant cutaneuos melanoma. J Clin Oncol 19: 824-831, 2001 23. Meyerhoffer S, Lindberg Z, Hager A, et al: Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in children. Acta Derm Venereol 78: 31-35, 1998 24. Sasaki Y, Shimizu H, Naka W, et al: Evaluation of the clinical usefulness of measuring urinary excretion of 5-S-cysteinyldopa in melanoma: ten years experience of 50 patients. Acta Derm Venerol 77: 379-381, 1998 25. Seregeni E, Massaron S, Martinetti A, et al: S-100 protein serum levels in cutaneous malignant melanoma. Oncol Rep 5: 601-604, 1998 26. Schmitz C, Brenner W, Henze E, et al: Comparative study on the clinical use of protein S-100 B and MIA in melanoma patients. Anticancer Res 20: 5059-5063, 2000 27. Schoultz ES, Diepgen TL, von den Dresch P: Clinical prognostic relevance of serum S-100b protein in malignant melanoma. Br J Dermatol 38: 426-430, 1998 28. Wakamatsu K, Ito S: Seasonal variations in serum concentration of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2- carboxyl acid in healthy Japanese. Pigment Cell Res 8: 132- 134, 1995 29. Wibe E, Hannisdal E, Paus E, Aamdal S: Neuron-specific enolase as prognostic factor in metastatic melanoma. Eur J Cancer 28: 1692-1695, 1992 30. Wimmer I, Meyer CJ, Seifert B, et al.: Prognostic value of serum 5-S-cysteinyldopa for monitoring human metastatic melanoma during immunochemoterapy. Cancer Res 57: 5073- 5076, 1997
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 183
EP 187
PG 5
ER
PT J
AU Gumurdulu, D
Zeren, H
Cagle, TP
Kayaselcuk, F
Alparslan, N
Kocabas, A
Tuncer, I
AF Gumurdulu, Derya
Zeren, E. Handan
Cagle, T Philip
Kayaselcuk, Fazilet
Alparslan, Nazan
Kocabas, Ali
Tuncer, Ilhan
TI Specificity of MOC-31 and HBME-1 Immunohistochemistry in the Differential Diagnosis of Adenocarcinoma and Malignant Mesothelioma: a Study on Environmental Malignant Mesothelioma Cases from Turkish Villages
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB Histological diagnosis of malignant mesothelioma (MM) and differentiation from adenocarcinoma is often difficult. A number of clinical, radiologic, histologic and histochemical criteria have been used as diagnostic aids, but most cases cannot be readily classified on the basis of these characteristics. In recent years, a panel of immunohistochemical anti-bodies have been increasingly applied for the differential diagnosis of these two tumors. MOC-31 has been recently used as specific for adenocarcinomas while reacting with a minimal number of benign and malignant mesothelial proliferations, and HBME-1 has also been presented as a mesothelial cell marker. In this study, we aimed to show the importance of these two antibodies among the environmental MM cases from Southeastern Turkey. Fifty five cases of MM and twenty adenocarcinomas were included in this study. Histochemical (PAS, PAS-D, mucicarmine) and immunohistochemical (Keratin, EMA,CEA, MOC-31, HBME-1) stains have been performed on each case. Keratin was positive in all cases. EMA stained 50 of 55 MM and all the adenocarcinoma cases. According to our results, dPAS, mucicarmen, CEA and MOC-31 positivity was statistically significant in the diagnosis of adenocarcinoma whereas HBME-1 was demonstrable in most MM cases (52/55) and 11 adenocarcinoma cases. This study confirmed that in the diagnostic distinction between MM and adenocarcinoma, immuno-histochemistry is an important diagnostic tool, however, a panel of antibodies must be used rather than any single antibody. HBME-1 should be included in this panel; MOC-31 can be used where CEA is not available or to doublecheck the reactivity of this antibody.
C1 [Gumurdulu, Derya] Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
[Zeren, E. Handan] Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
[Cagle, T Philip] Univeristy of Houston, Department of PathologyHouston, USA.
[Kayaselcuk, Fazilet] Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
[Alparslan, Nazan] Cukurova University, Faculty of Medicine, Department of BiostatisticsAdana, Turkey.
[Kocabas, Ali] Cukurova University, Faculty of Medicine, Department of Pulmonary MedicineAdana, Turkey.
[Tuncer, Ilhan] Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
CR Sheibani K, Battifora H, Burke JS: Antigenic phenotype of malignant mesothelioma and pulmonary adenocarcinomas. Am J Pathol 123: 212-219, 1986
Sosolik RC, Mcgaughy VR, De Young BR: Anti-MOC-31: A potential addition to the pulmonary adenocarcinoma versus mesothelioma immunohistochemistry panel. Mod Pathol 10: 716-719, 1997
Donna A, Betta PG, Chiodera P, et al: Newly marketed tissue markers for malignant mesothelioma: Immunoreactivity of rabbit AMAD-2 antiserum, compared with monoclonal antibody HBME-1 and a review of the literature on so-called antimesothelioma antibodies. Hum Pathol 28: 929-937, 1997
Zeren EH, Gumurdulu D, Roggli VL, et al: Environmental Malignant Mesothelioma in Southern Anatolia: A study of fifty cases. Environ Health Perspect 108: 1047-1050, 2000
Warnock ML, Stoloff A, Thor A: Differentiation of adenocarcinoma of the lung from mesothelioma: periodic acid schiff, monoklonal antibodies B 72.3 and leu M1. Am J Pathol 133: 30-38, 1988
Brown RW, Clark GM, Tandon AK, et al: Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma. Hum Pathol 24: 347-354, 1993
Skov BG, Lauritzen AF, Hirsch F, et al: The histopathological diagnosis of malignant mesothelioma v.pulmonary adenocarcinoma: reproducibility of the histopathological diagnosis. Histopathology 24: 553-557, 1994
Skov B, Lauritzen AF, Hirsch F, et al: Differantiation of adenocarcinoma of the lung and malignant mesothelioma: Predictive value and reproducibility of immunoreactive antibodies. Histopathology 25: 431-437, 1994
Wirth PR, Legier J, Wright GL: Immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma. Cancer 67: 655-662, 1991
Zeng L, Feith J, Monnet I, et al: Immunocytochemical characterization of cell lines from human malignant mesothelioma: characterization of human mesothelioma cell lines by immunocytochemistry with a panel of monoclonal antibodies. Hum Pathol 25:3: 227-234, 1994
Cagle PT, Truong LD, Roggli VL, et al: Immunohistochemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms. Am J Clin Pathol 92: 566-571, 1989
Sheibani K, Esteban JM, Bailey A, et al: Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol 23: 107-116, 1992
Bateman AC, Al-Talib RK, Newman T: Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA 125 and HBME-1 expression. Histopathology 30: 49-56, 1997
Dejmek A, Hjerpe A: Immunohistochemical reactivity in mesothelioma and adenocarcinoma: A stepwise logistic regression analysis. APMIS 102: 255-264, 1994
Battifora H, Kopinski MI: Distinction of mesothelioma from adenocarcinoma. Cancer 55: 1679-1685, 1985
Kortsik CS, Werner P, Freudenberg N, et al: Immunocytochemical characterization of malignant mesothelioma and carcinoma metastatic to the pleura: IOB3- a new tumor marker. Lung 173: 79-87, 1995
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Mezger J, Lamerz R, Permanetter W: Diagnostic significance of carcinoembryonic antigen in the differantial diagnosis of malignant mesothelioma. J Thorac Cardiovasc Surg 100: 860- 866, 1990
Morgan RL, De Young BR, McGaughy VR, et al: MOC-31 aids in the differentiation between adenocarcinoma and reactive mesothelial cells. Cancer 87: 390-394, 1999
Edwards C, Oates J: OV 632 and MOC-31 in the diagnosis of mesothelioma and adenocarcinoma: an assessment of their use in formalin fixed and paraffin wax embedded material. J Clin Pathol 48: 626-630, 1995
Ordonez NG: Value of the MOC-31 monoclonal antibody in differentiating epithelial pleural mesothelioma from lung adenocarcinoma. Hum Pathol 29: 166-169, 1998
Attanoos RL, Goddard H, Gibbs AR: Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. Histopathology 29: 209-215. 1996
Kennedy AD, King G, Kerr KM: HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura. J Clin Pathol 50: 859-862, 1997
Fetsch PA, Abati A, Hijazi YM: Utility of the antibodies CA 19- 9, HBME-1 and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology. Cancer 84: 101-108, 1998
Riera JR, Astengo-Osuna C, Longmate JA,et al: The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat induced epitope retrieval. Am J Surg Pathol 21: 1409-1419, 1997
Cury PM, Butcher DN, Fisher C, et al: Value of the mesothelium- associated antibodies thrombomodulin, cytokeratin 5/6, calretinin and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol 13: 107-112, 2000
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 188
EP 193
PG 6
ER
PT J
AU Noorali, S
Nausheen, Y
Nasir, IM
Moatter, T
Pervez, Sh
AF Noorali, Samina
Nausheen, Yaqoob
Nasir, Israr Muhammad
Moatter, Tariq
Pervez, Shahid
TI Prevalence of Mycosis Fungoides and Its Association with EBV and HTLV-1 in Pakistanian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB Mycosis fungoides (MF) is an indolent T cell lymphoma that is distinguished from other lymphomas by its initial appearance on the skin. The histologic diagnosis of MF may be difficult because there is significant overlap in the histologic features of neoplastic T-cell infiltrates and inflammatory dermatoses. This T-cell neoplasm commonly occurs in a mixed, reactive background and can show only a subtle degree of cytologic atypia, rendering histologic diagnosis difficult. In this study MF constituted 0.86% of all non-Hodgkin’s lymphoma (NHL) both T and B, as compared to the Western studies which have reported 0.5% prevalence for MF of all NHL. Polymerase chain reaction (PCR) technique was used to assess T-cell clonality in paraffin-embedded skin biopsies clinically and pathologically suspicious for early MF. Out of the 14 cases diagnosed as MF, amplifiable DNA was isolated from 6 cases, which were further studied for T-cell receptor (TcR) – b b, g g, and d dchain gene rearrangements. Clonal product was seen in 4 out of 6 cases for b b, g g, and d dTcR chain genes. Association for Epstein Barr virus (EBV) was observed in 3 out of 6 cases (50%) of MF. Although these 3 cases were positive for EBV by PCR, but were negative by in-situ hybridization (ISH). No heterogeneity was noted in these 3 cases of MF for BamHI E, K, N, and Z regions of EBV. All six cases were negative for HTLV-1 (tax region) by PCR. It was concluded that the prevalence of MF in Pakistani population is comparable to the Western data, and that EBV association to MF cases was higher than in Western studies.
C1 [Noorali, Samina] The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
[Nausheen, Yaqoob] The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
[Nasir, Israr Muhammad] The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
[Moatter, Tariq] The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
RP Pervez, Sh (reprint author), The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
EM shahid.pervez@aku.edu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 194
EP 199
PG 6
ER
PT J
AU Kacar, F
Meteoglu, I
Sen, S
Levi, E
AF Kacar, Furuzan
Meteoglu, Ibrahim
Sen, Serdar
Levi, Edi
TI Primary Neuroendocrine Carcinoma of the Mediastinum
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
AB A mediastinal mass was found in a 37 year old male who presented with fever, weight loss and fatigue. The chest CT revealed a 9x6x4 cm well circumscribed mass located paratracheally in the upper mid-mediastinum. The mass was removed by right thoracotomy. Macroscopically the tumor weighed 195 g and measured 9x6x4 cm. Microscopically the tumor consisted of small blue cells in solid and trabeculer patern. Immunohistochemical studies performed for differential diagnosis of small blue cell tumors. The tumor was diagnosed as primary neuroendocrine carcinoma of the mediastinum. This case is presented for its rare recurrence in that particular location.
C1 [Kacar, Furuzan] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Meteoglu, Ibrahim] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Sen, Serdar] Adnan Menderes University, Faculty of Medicine, Department of Thoracic SurgeryAydin, Turkey.
[Levi, Edi] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
RP Kacar, F (reprint author), Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
EM furuzankacar@hotmail.com
CR Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors. Cancer 79: 813-829, 1997
Wick MR, Rosai J: Neuroendocrine neoplasms of the mediastinum. Semin Diagn Pathol 8: 35-51, 1991
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Horenstein MG, Erlandson RA, Gonzalez-Cueto DM, Rosai J: Presacral carcinoid tumors: report of three cases and review of the literature. Am J Surg Pathol 22: 251-255, 1998
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Horie Y, Keto M: Neuroendocrine carcinoma of the posterior mediastinum. A possible primary lesion. Arch Pathol Lab Med 123: 933-936, 1999
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Wick MR, Scheithauer BW. Thymic carcinoid: a histologic, immunohistochemical and ultrastructural study of 12 cases. Cancer 53: 475-484, 1984
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 200
EP 201
PG 2
ER
PT J
AU Repassy, LD
Ivanyi, A
Csata, S
Tamas, Gy
AF Repassy, Laszlo Denes
Ivanyi, Andras
Csata, Sandor
Tamas, Gyorgy
TI Combined Occurrence of Prostate Carcinoma and Malacoplakia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
AB This is a case of a 56-year-old male patient suffering from a combination of prostate carcinoma and malacoplakia. A 56-year-old male patient was admitted in our Departement because ischuria due to the enlargement of the prostate. Perineal needle biopsy was done resulting carcinoma of prostatae. Radical prostatectomy was performed. Histology proved carcinoma and a great part of the enlarged prostate consisted of malacoplakia. Questions related to the morphology, tissue structure as well as diagnosis are briefly surveyed. This is the first report on the rarely occurring combination of prostate carcinoma and malacoplakia treated by radical retropubic prostatectomy.
C1 [Repassy, Laszlo Denes] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1, H-1096 Budapest, Hungary.
[Ivanyi, Andras] Municipal Hospital, Del-Pest, Department of PathologyBudapest, Hungary.
[Csata, Sandor] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1, H-1096 Budapest, Hungary.
[Tamas, Gyorgy] Saint Stephen Hospital, Department of Urology, Nagyvarad ter 1, H-1096 Budapest, Hungary.
RP Repassy, LD (reprint author), Saint Stephen Hospital, Department of Urology, H-1096 Budapest, Hungary.
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Liu S, Christmas TJ, Kirby RS: Malakoplakia and carcinoma of the prostate. Br J Urol 72:120-121, 1993
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 202
EP 203
PG 2
ER
PT J
AU Timar, J
Csuka, O
Orosz, Zs
Jeney, A
Kopper, L
AF Timar, Jozsef
Csuka, Orsolya
Orosz, Zsolt
Jeney, Andras
Kopper, Laszlo
TI Molecular Pathology of Tumor Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
AB Molecular Pathology of Tumor Metastasis With the development of non-invasive methods, diagnosis of metastasis from various solid malignancies has become a routine task for diagnostic pathology. However, the differential diagnosis between primary and metastatic cancers and the precise identification of various metastatic cancer types requires the coordinated use of various morphological (light- and electron microscopic-), immunological and molecular techniques. The detection of the lymphatic spread of the primary tumor may now based on the sentinel lymph node technology while the identification of the hematogenous progression may be based on the analysis of the peripheral blood and the bone marrow. More and more frequently these techniques employ highly sensitive immunological and molecular techniques. Accordingly, clinical staging is now confronted with the results of molecular staging, where the only techniques which are able to detect cancer cells are immunocytochemistry or nucleic acid-based methodology. Although several clinical studies have provided evidences for the impact of the immunocytochemistry-based identification of micrometastases on the survival of patients with various type of cancers, none of these methods have become part of standard diagnostic protocols. Although more sensitive molecular techniques are being introduced to identify micrometastasis, their clinical significance is yet unknown. Multicentric clinical trials are now warranted to establish the clinical impact of molecular staging in various cancer types. Without the integration of these methods into the prognostic/predictive pathological protocols it is difficult to envision significant improvement in the results of cancer therapy.
C1 [Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Csuka, Orsolya] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2002
VL 8
IS 3
BP 204
EP 219
PG 16
ER
PT J
AU Zvara,
Hackler, L
Nagy, BZs
Micsik, T
Puskas, GL
AF Zvara, Agnes
Hackler, Laszlo
Nagy, B Zsolt
Micsik, Tamas
Puskas, G Laszlo
TI New Molecular Methods for Classification, Diagnosis and Therapy Prediction of Hematological Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE molecular methods; DNA-chip; oncohematology
ID molecular methods; DNA-chip; oncohematology
AB Normal functions of the cell are based on the precise regulation of various genes. If this strict regulation and the hierarchy of genes becomes upset due to flaws in this system, the result will be cellular dysfunction which eventually may lead to carcinogenic transformation. Two basic challenges of the classification of cancers are the discovery of new molecular markers characteristic to defined disease groups and the classification of already diagnosed or new cases into existing groups. This precise classification may open the door to tailored treatment or project the expected outcome of the disease. Today there is unlimited access available to the databases containing sequences and localization of the genes within the confines of Human Genome project. It provides significant help for the discovery of chromosome abnormalities and systematic analysis of gene expression patterns. This is important not only to understand normal functions of the cells, but it also contributes to the identification of new genes that are characteristic to given disease groups as markers and that are potential drug targets. Until the second half of the twentieth century the study of the function and regulation of genes was based on step-by-step investigation of individual genes. Regarding the fact, that the genomes of an increasing number of organisms have become known in whole or in part, numerous new techniques have been developed that facilitated the systematic analysis of gene functions. The aim of this study is to summarize the new, molecular based possibilities for classification, diagnosis and prognosis of hematological malignancies, as well as to summarize the main results of these areas.
C1 [Zvara, Agnes] University of Szeged, Department of Medical Genetics, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Hackler, Laszlo] University of Szeged, Department of Medical Genetics, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Nagy, B Zsolt] University of Szeged, Department of Medical Genetics, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Micsik, Tamas] University of Szeged, Department of Medical Genetics, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Puskas, G Laszlo] University of Szeged, Department of Medical Genetics, Temesvari krt. 62, H-6726 Szeged, Hungary.
RP Puskas, GL (reprint author), University of Szeged, Department of Medical Genetics, H-6726 Szeged, Hungary.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 231
EP 240
PG 10
ER
PT J
AU Girolami, F
Passerini, I
Gargano, D
Frusconi, S
Villari, D
Nicita, G
Torricelli, F
AF Girolami, Francesca
Passerini, Ilaria
Gargano, Dorotea
Frusconi, Sabrina
Villari, Donata
Nicita, Giulio
Torricelli, Francesca
TI Microsatellite Analysis of Chromosome 3p Region in Sporadic Renal Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microsatellite instability; renal cell carcinoma; LOH; RER
ID microsatellite instability; renal cell carcinoma; LOH; RER
AB The etiology and progression of renal carcinomas (RCC) is still poorly understood. RCC have been classified into several pathological entities. The most frequent type, clear cell carcinoma, accounts for about 80% of sporadic RCC and shows several chromosome abnormalities documented both by conventional cytogenetics, loss of eterozygosity (LOH) and replication error (RER) studies. In 10 clear cell type sporadic RCC we evaluated LOH and RER using a set of 10 microsatellite markers covering the chromosome 3p region, which has been suggested for interstitial deletions. Electrophoresis was performed by automated sequencer ABI Prism 377 and data were analyzed with Genescan and Genotyper 2.5 softwares. We revealed allelic loss in 48,7% of informative microsatellites and a single case of RER. We found the highest LOH frequency in 3p25-26 region where maps Von Hippel-Lindau (VHL) oncosuppressor gene. In addition, DNA hypermethylation, an alternative mechanism of VHL gene silencing, was evaluated by methylation-specific PCR. However hypermethylation status was not detected in any of our tumor samples.
C1 [Girolami, Francesca] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Passerini, Ilaria] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Gargano, Dorotea] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Frusconi, Sabrina] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Villari, Donata] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Nicita, Giulio] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
[Torricelli, Francesca] Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, V.le Morgagni n.85, 50134 Firenze, Italy.
RP Girolami, F (reprint author), Azienda Ospedaliera Careggi and II Urological Clinic, Cytogenetics and Genetics Unit, 50134 Firenze, Italy.
EM citogenbibl@ao-careggi.toscana.it
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Velickovic M, Delahunt B, Storkel S, et al: VHL and FHIT locus loss of heterozygosity in common in all renal cancer morphotypes but differs in pattern and prognostic significance. Cancer Res 61: 4815-4819, 2001
Meyer AJ, Hernandez A, Florl AR, et al: Novel mutations of the Von Hippel Lindau tumor- suppressor gene and rare DNA hypermethylation in renal cell carcinoma cell lines of the clearcell type. Int J Cancer 87:650-653, 2000
Chino K, Esumi M, Ishida H, et al: Characteristic loss of heterozygosity in chromosome 3p and low frequency of replication errors in sporadic renal cell carcinoma. J Urol 162: 614- 618, 1999
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 241
EP 244
PG 4
ER
PT J
AU Smardova, J
Pavlova, S
Koukalova, H
AF Smardova, Jana
Pavlova, Sarka
Koukalova, Hana
TI Determination of Optimal Conditions for Analysis of p53 Status in Leukemic Cells Using Functional Analysis of Separated Alleles in Yeast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor suppressor p53; FASAY; DNA polymerase fidelity; mRNA stability
ID tumor suppressor p53; FASAY; DNA polymerase fidelity; mRNA stability
AB Tumor suppressor p53 is transcription factor that participates in control of many cellular functions. Somatic mutations of the p53 gene are frequently detected in human cancers. Several methods can be used for identification of p53 mutations, including FASAY - functional analysis of separated alleles in yeast. FASAY distinguishes yeast colonies expressing functional p53 protein from colonies producing a dysfunctional p53 protein simply on the basis of color. The validity of the method depends on a low background level. There are several sources of background as PCR-induced point mutations, low quality of RNA and alternative splicing of intron 9 affecting the p53 carboxy-terminus. In the present work we show that FASAY can be successfully used for analysis of mRNA isolated from blood samples that were collected and stored for 24 hours at 0°C without undesired increase of background. We also measured fidelity of several commonly used DNA polymerases and determined the most suitable kinds of Pfu DNA polymerases for FASAY. Reaction conditions described in this report allow routine analysis of p53 status in leukemic cells using FASAY.
C1 [Smardova, Jana] Masaryk Memorial Cancer Institute, Department of Experimental Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.
[Pavlova, Sarka] Masaryk Memorial Cancer Institute, Department of Experimental Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.
[Koukalova, Hana] Masaryk Memorial Cancer Institute, Department of Experimental Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.
RP Smardova, J (reprint author), Masaryk Memorial Cancer Institute, Department of Experimental Oncology, 656 53 Brno, Czech Republic.
EM smardova@mou.cz
CR Baker SJ, Markowitz S, Fearon ER, et al: Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249: 912-915, 1990
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 245
EP 251
PG 7
ER
PT J
AU Ghaderi, A
Vasei, M
Maleck-Hosseini, AS
Gharesi-Fard, B
Khodami, M
Doroudchi, M
Modjtahedi, H
AF Ghaderi, Abbas
Vasei, Mohammad
Maleck-Hosseini, A S
Gharesi-Fard, Behronz
Khodami, Maliheh
Doroudchi, Mehrnoosh
Modjtahedi, Helmout
TI The Expression of c-erbB-1 and c-erbB-2 in Iranian Patients with Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-erbB-1; c-erbB-2; gastric carcinoma; southern Iranian
ID c-erbB-1; c-erbB-2; gastric carcinoma; southern Iranian
AB To assess the significance of epidermal growth factor receptor family members, the overexpression of c-erbB-1 and c-erbB-2 was retrospectively investigated in 146 southern Iranian gastric cancer patients. Indirect immunostaining was used to evaluate the expression of these two receptors in formalin-fixed paraffin-embedded tissue samples. c-ErbB-1 expression was observed in 47 (32.2%) and c-erbB-2 expression was observed in 24 (16.4%) of tumors. Significant positive correlations were observed between c-erbB-1 expression and tumor size, local invasion, lymph node involvement and tumor stage. There was also a negative correlation between c-erbB-2 expression and tumor stage. These results may suggest the contribution of c-erbB-1 molecule in progression of gastric carcinomas in southern Iranian patients. Moreover, the relatively high percentage of c-erbB-2 positive tumors may provide a useful target for the immunotherapy of these cancers.
C1 [Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Vasei, Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Maleck-Hosseini, A S] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Gharesi-Fard, Behronz] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Khodami, Maliheh] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Doroudchi, Mehrnoosh] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Modjtahedi, Helmout] Medical School, Shiraz University of Medical Sciences, Department of SurgeryShiraz, Iran.
RP Ghaderi, A (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Pathology, Shiraz, Iran.
CR Farahmandbeigi M, Kadivar MR: The incidence rate of registered cancers in Fars province. Disease Control Unit, Shiraz University Press, Iran, 2000.
Koyama S, Maruyama T, Adachi S: Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: a twocolor flow-cytometric analysis. J Cancer Res Clin Oncol 125: 47-54, 1999.
Prakash I, Mathur RP, Kar P, et al: Comparative evaluation of cell proliferative indices and epidermal growth factor receptor expression in gastric carcinoma. Indi J Pathol Microbiol 40:481-490, 1997.
Jang WI, Yang WI, Lee CI, et al: Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma. J Korean Med Sci 8: 293-304, 1993.
Oshima CT, Lanzoni VP, Iriya K, Forones NM:C-erbB-2 oncoprotein in gastric carcinoma: correlation with clinical stage and prognosis. Int J Biol Markers 16: 250-254, 2001.
Wu MS, Shun CT, Sheu JC, et al: Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages. J Gastroenterol Hepatol 13: 305-310, 1998.
Lee HR, Kim JH, Uhm HD, et al: Overexpression of c-ErbB-2 protein in gastric cancer by immunohistochemical stain. Oncology 53: 192-197, 1996.
Aoyagi K, Kohfuji K, Yano S, et al: Evaluation of the epidermal growth factor receptor, EGFR, and c-erbB-2 in superspreading- type and penetrating-type gastric carcinoma. Kurume Med J 48:197-200, 2001.
Motojima K, Furui J, Kohara N, et al: erbB-2 expression in welldifferentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery 115:349-354, 1994.
Yoshida K, Yasui W, Ito H, Tahara E: Growth factors in progression of human esophageal and gastric carcinomas. Exp Pathol 40: 291-300, 1990.
Lee EY, Cibull ML, Strodel WE, Haley JV: Expression of HER- 2/neu oncoprotein and epidermal growth factor receptor and prognosis in gastric carcinoma. Arch Pathol Lab Med 118: 235-239, 1994.
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Tokunaga A, Onda M, Okuda T, et al: Prevention of growth of a human gastric cancer xenograft in nude mice with anti-EGF receptor ntibody. In: Takahashi T, editor. Recent advances in management of digestive cancers. Tokyo: Springer-Verlag, 403-405, 1993.
Teramoto T, Onda M, Tokunaga A, Asano G: Inhibitory effect of anti-epidermal growth factor receptor antibody on a human gastric cancer. Cancer 77s: 1639-1645, 1996.
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Modjtahedi H, Hickish T, Nicolson M, et al: Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer. Br J Cancer 73: 228- 235, 1996.
Bianco C, Bianco R, Tortora G, et al: Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. Clin Cancer Res 6: 4343-4350, 2000.
Ciardiello F, Bianco R, Damiano V, et al: Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res 6: 3739-47, 2000.
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Takehana T, Kunitomo K, Kono K, et al: Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzymelinked immuno-sorbent assay. Int J Cancer 98: 833-837, 2002.
Gharesi-Fard B, Vasei M, Talei A, et al: The expression and prognostic significance of c-erbB-2 molecules in patients with breast cancer in Iran. Irn J Med Sci 25: 31-35, 2000.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 252
EP 256
PG 5
ER
PT J
AU Elo, J
Balatoni, Zs
Kotai, Zs
Bartfai, R
AF Elo, Janos
Balatoni, Zsuzsa
Kotai, Zsuzsa
Bartfai, Reka
TI Considerations in the Treatment of the Node-negative (N0) Neck in Glottic Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glottic cancer; N0 neck; predictive factors; therapy
ID Glottic cancer; N0 neck; predictive factors; therapy
AB Treatment of lymph node negative (N0) glottic carcinoma has raised numerous controversy for decades. Prevention is one of the oldest axioms in medicine. On the other hand, overtreatment can cause unnecessary harm to patients. This retrospective study was performed in 206 patients having glottic cancers with clinically node-negative (N0) necks. The aim of this assessment is to deal with the diagnosis, predictive factors and surgical therapy of occult metastases of squamous cell cancers originating from the glottic region. The examinations were performed in three phases. Preoperative clinical, histological - and in selective cases - imaging were carried out to separate high-risk patients. Intraoperative cases of open surgery after U-shaped skin preparation up to the hyoid bone with direct inspection of jugular lymph node chain (JLNCh) where the neck was staged. The enlarged suspicious nodes were submitted for immediate frozen section. The types of neck dissection were based on the size, shape, number and histological diagnosis of regional nodes. The postoperative additional management was decided according to the results of definitive pathological findings from serial sections of the dissected specimen. Endolaryngeal LASER surgery was carried out in 87 patients based on clinical, histological and imaging criteria. In the course of two years follow-up 2 occult metastases became clinically apparent. At 119 cases open surgery were performed. In 51 patients we could not see enlarged lymph nodes (N< 2 mm) with direct examination, and thus the JLNCh remained intact. In 68 patients elective neck dissections (END) were carried out. In cases of extracapsular spread (ECS) and/or multiple nodal involvements additional radiotherapy was given.
C1 [Elo, Janos] Uzsoki University Teaching Hospital, Department of ENT and Head-Neck Surgery, Uzsoki u. 29, H-1145 Budapest, Hungary.
[Balatoni, Zsuzsa] Uzsoki University Teaching Hospital, Department of ENT and Head-Neck Surgery, Uzsoki u. 29, H-1145 Budapest, Hungary.
[Kotai, Zsuzsa] Uzsoki University Teaching Hospital, Department of ENT and Head-Neck Surgery, Uzsoki u. 29, H-1145 Budapest, Hungary.
[Bartfai, Reka] Uzsoki University Teaching Hospital, Department of ENT and Head-Neck Surgery, Uzsoki u. 29, H-1145 Budapest, Hungary.
RP Elo, J (reprint author), Uzsoki University Teaching Hospital, Department of ENT and Head-Neck Surgery, H-1145 Budapest, Hungary.
CR Ganzer U, Sandrowski P, Vosteen KH, Meyer-Breiting F: Die kombinierte radio-chirurgische Behandlung des fortgeschrittenen Kehlkopfkarzinoms, T3-T4, Laryngol Rhinol 60:63-70, 1981
Snow GB: The N0 neck in head and neck cancer patients. Eur Arch Otorhinolaryngol 250:423-424, 1993
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Lenz M, Kersting-Sommerhof B, Gross MD: Diagnosis and treatment in N0-neck in carcinoma of the upper aerodigestive tract: current status of diagnostic procedures. Eur Arch Otorhinolaryngol 250:432-438, 1993
Steiner W, Hommerich CP: Diagnoses and treatment of the N0 neck of carcinomas of the upper aerodigestive tract. Eur Arch Otorhinolaryngol 250:450-456, 1993.
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O’Brien ChJ, Traynor SJ, McNeil ÍE, et al: The use of clinical criteria alone in the management of clinically negative neck among patients with squamous cell carcinoma of the oral cavity and oropharynx. Ach Otolaryngol Head Neck Surg 126:360-365, 2000.
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Schantz SP: Biologic markers, cellular differentation and metastatic head and neck cancer. Eur Arch Otorhinolaryngol 250:424-428, 1993.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 257
EP 261
PG 5
ER
PT J
AU Canoz,
Belenli, O
Patiroglu, ET
AF Canoz, Ozlem
Belenli, Olcay
Patiroglu, E Tahir
TI General Features of Gastric Carcinomas and Comparison of HSP70 and NK cell Immunoreactivity with Prognostic Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric carcinoma; HSP70; NK-cell; prognostic factors
ID gastric carcinoma; HSP70; NK-cell; prognostic factors
AB During the period of 1996-1998 ninety-four gastrectomy specimens with gastric carcinoma referred to Erciyes University, Medical Faculty, Department of Pathology, were examined histopathologically, histochemically and immunohistochemically. General characteristics of gastric carcinomas and prognostic factors were studied. According the Lauren classification, of the 94 cases of gastric carcinomas, 56 were intestinal type, 21 were diffuse type and 17 were mixed type carcinoma. The association rates of Helicobacter pylori, chronic atrophic gastritis and intestinal metaplasia with gastric carcinomas were high. There was strong immunorectivity with HSP70 in 62,5% of the intestinal type carcinomas. This ratios were lower in diffuse and mixed type carcinomas (p<0.05). The more tumor size and invasion depth increased, the more HSP70 immunoreactivity was obtained (p<0.05). HSP70 immunorectivity was considerably higher in the patients having lymph node metastasis and vascular invasion (p<0.05). It was found that the NK cell number was low in the tumor but higher around the tumor in early gastric carcinomas, compared with advanced carcinomas (p>0.05). In the tumors larger than 10 cm with vascular invasion, NK cell number was lower around the tumor (p>0.05). Defining prognostic factors of gastric carcinomas is of importance to clinicians. It is thought that HSP70 immunoreactivity, besides invasion depth, lymph node metastasis, vascular invasion, tumor size and inflammatory reaction against the tumor, is important in prognosis and associated with advanced stage.
C1 [Canoz, Ozlem] Medical Faculty of Erciyes University, Pathology Department, MKP Bulvari, Zumrut mah, Hukukcular Sit. B-Blok No:15Kocasinan / Kayseri, Turkey.
[Belenli, Olcay] Medical Faculty of Duzce Abant Izzet Baysal University, Pathology DepartmentDuzce, Turkey.
[Patiroglu, E Tahir] Medical Faculty of Erciyes University, Pathology Department, MKP Bulvari, Zumrut mah, Hukukcular Sit. B-Blok No:15Kocasinan / Kayseri, Turkey.
RP Canoz, (reprint author), Medical Faculty of Erciyes University, Pathology Department, Kocasinan / Kayseri, Turkey.
EM ocanoz@erciyes.edu.tr
CR Davessar K, Pezzullo JC, Kessimian N, et al: Gastric adenocarcinoma: prognostic significance of several pathologic parameters and histologic classifications. Hum Pathol 21:325-332, 1990
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 262
EP 269
PG 8
ER
PT J
AU Romics, I
Riesz, P
Szelepcsenyi, J
Nyirady, P
AF Romics, Imre
Riesz, Peter
Szelepcsenyi, Janos
Nyirady, Peter
TI Bilateral Renal Cell Carcinoma in a Horseshoe Kidney
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE renal cell carcinoma; horseshoe kidney; radical nephrectomy
ID renal cell carcinoma; horseshoe kidney; radical nephrectomy
AB We report a case of bilateral renal cell carcinoma in a horseshoe kidney. To the best of our knowledge this is the second reported case in the international literature. We performed different radiological examinations preoperatively to identify of blood supply, because correct preoperative location of vessels is mandatory.
C1 [Romics, Imre] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1082 Budapest, Hungary.
[Riesz, Peter] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1082 Budapest, Hungary.
[Szelepcsenyi, Janos] General PractitionerNagykata, Hungary.
[Nyirady, Peter] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1082 Budapest, Hungary.
RP Romics, I (reprint author), Semmelweis University, Department of Urology, H-1082 Budapest, Hungary.
EM romimre@urol.sote.hu
CR Bauer S, Perlmutter A, Retik A: Anomalies of the upper urinary tract. In: Campbell’s Urology, 6th ed., Eds: Walsh PC, Retik AB, Stamey TA, Vaughan ED Jr), W.B. Saunders Philadelphia, pp 1357-1442, 1992
Brum FA, Becker M, Uglione A, Da Ros CT: Polycystic horseshoe kidney. J Urol 158: 2229-2232, 1997
Cuckow PM, Nyirady P: Embryology of the Urogenital Tract. In: Pediatric Urology., Eds: Gearhart JP, Rink RC, Mouriquand PDE), W.B. Saunders, Philadelphia, pp. 3-13, 2001
Fisher RM, Frank JD: Abnormal Migration and Fusion of the Kidneys. In: Pediatric Urology., Eds: Gearhart JP, Rink RC, Mouriquand PDE), W.B. Saunders, Philadelphia, pp. 275-278, 2001
Schubert RA, Soldner J, Steiner T, et al: WA: Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital substraction angiography. Eur Radiol 8:1694- 1697, 1998
Smith RB, deKernion JB, Ehrlich RM, et al: Bilateral renal cell carcinoma and renal cell carcinoma in the solitary kidney. J Urol 132: 450-455, 1984
Thomas DFM, Cook JA: Perinatal Urology. In Textbook of Genitourinary Surgery,2nd ed., Eds: Whitfield HN, Hendry WF, Kirby RS, Duckett JW), Blackwell Science, Oxford, pp. 133- 143, 1998
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 270
EP 271
PG 2
ER
PT J
AU Arista-Nasr, J
Nuncio, J
Martinez, B
AF Arista-Nasr, Julian
Nuncio, Juan
Martinez, Braulio
TI Atypical Histiocytic Infiltration Simulating Diffuse-type Carcinoma in a Gastric Ulcer due to Non-Steroidal Anti-Inflammatory Drugs
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE atypical; histiocytic; gastric; ulcer; NSAID
ID atypical; histiocytic; gastric; ulcer; NSAID
AB A 83-year old man treated with naproxen during two years was admitted because of hypovolemia and peritoneal irritation. A panendoscopic study was performed and an ulcer localized at the large curvature of the stomach was disclosed. In the gastrectomy specimen the ulcer showed necrosis, edema, fibrosis, chronic inflammatory infiltrate with lymphocytes and plasma cells. Additionally, atypical cells with irregular and hyperchromatic nuclei or vacuolated cytoplasm were seen in the lamina propia and infiltrating the muscular layers; isolated signet-ring-like cells were also seen. Histochemical study with periodic acid-Schiff, mucicarmin, and colloidal stains revealed mucosubstances in these cells. A poorly differentiated carcinoma was initially diagnosed. However, the immunohistochemical study were positive for histiocytic markers (CD-68, S-100 protein) and negative for epithelial markers (cytokeratin; and epithelial membrane antigen). The positivity of mucus stains in the histiocytes could be explained in this case by phagocytosis of mucous substances released from broken hyperplastic glands in the vicinity of the ulcer. To our knowledge, atypical histiocytic infiltration in gastric ulcers has not been previously described; thus, it should be included in the group of gastric carcinoma mimicks.
C1 [Arista-Nasr, Julian] Instituto Nacional de la Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15, Tlalpan, 14000 Mexico City, Mexico.
[Nuncio, Juan] Instituto Nacional de la Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15, Tlalpan, 14000 Mexico City, Mexico.
[Martinez, Braulio] Instituto Nacional de la Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No.15, Tlalpan, 14000 Mexico City, Mexico.
RP Arista-Nasr, J (reprint author), Instituto Nacional de la Nutricion Salvador Zubiran, Department of Pathology, 14000 Mexico City, Mexico.
EM pipa5@hotmail.com
CR Humphries TJ. Gastric xantomata: The need for recognition. J Clin Gastroenterol 4:275-276, 1982.
Drude RB, Balart LA, Herrington JP, et al: Gastric xantoma: histologic similarity to signet ring cell carcinoma. J Clin Gastroenterol 4:217-221, 1982.
Arista-Nasr J, Jimenez A, Keirns C, et al: The role of endoscopic biopsy in the diagnosis of gastric lymphoma. Hum Pathol 22:339-348, 1991.
Zamboni G, Franzin G, Scarpa A, et al: Carcinoma-like signetring cells in gastric mucosa-associated lymphoid tissue, MALT, lymphoma. Am J Surg Pathol 20:588-598, 1996.
Arista-Nasr J, Romero-Lagarza P, Pichardo R. Artifactual signet-ring-like cells in endoscopic biopsy of gastric lymphoma. Arch Pathol Lab Med 121:623-625, 1997.
Taha AS, Nakshabendi I, Lee FD et al. Chemical gastritis and Helicobacter pylori related gastritis in patients receiving nonsteroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration. J Clin Pathol 45:135-139, 1992.
Lanza FL, Royer GL, Nelson RS: Endoscopic evaluation of the effect of aspirin, buffered aspirin and enteric-coated aspirin on gastric and duodenal mucosa. N Engl J Med 303:136-138, 1980.
Dixon MF, O´Connor HJ, Axon ATR et al: Reflux gastritis: distinct histopathological entity?. J Clin Pathol 39:524-530, 1986.
Quinn M, Bjarnason I, Price AB: Gastritis in patients on nonsteroidal anti-inflammatory drugs. Histopathology 23:341-348, 1993.
El-Zimaity HMT, Genta RM, Graham DY: Histological features do not define NSAID-induced gastritis. Hum Pathol 27:1348- 1354, 1996
Ball PAJ, James AH: The histological background to gastric ulcer. Lancet 1:1365-1367, 1961
Ogawa Y, Inada K, Tsutsumi Y: CD68 reactive histiocytosis complicating early gastric cancer. Pathol Int. 45:698-701, 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 272
EP 274
PG 3
ER
PT J
AU Kayaselcuk, F
Tuncer, I
Toyganozu, Y
Bal, N
Gursel,
AF Kayaselcuk, Fazilet
Tuncer, Ilhan
Toyganozu, Yavuz
Bal, Nebil
Gursel, Ozgur
TI Carcinosarcoma of the Stomach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE carcinosarcoma; immunohistochemistry; stomach
ID carcinosarcoma; immunohistochemistry; stomach
AB In the gastrointestinal tract, carcinosarcomas are most frequently seen in the esophagus. Carcinosarcoma in the stomach is a rare tumor. We report a carcinosarcoma of the antrum of stomach. The tumor was polypoid and exophytic in appearance and located in the antrum. Immunohistochemical studies showed positivity for cytokeratin, epithelial membrane antigen and cytoplasmic carcinoembryonic antigen in the epithelial component. Positive staining with vimentin, desmin and focal smooth muscle actin and negative staining with chromogranin were observed in spindle cells. Nuclear positive staining was observed with p53 and Ki-67 in both glandular and spindle atypical cells.
C1 [Kayaselcuk, Fazilet] Baskent University Faculty of Medicine, Department of Pathology, Adana Hospital, Seyhan Hospital, Dadaloglu mah. 39 Sk. No 6, 01250 Yuregir, Adana, Turkey.
[Tuncer, Ilhan] Baskent University Faculty of Medicine, Department of Pathology, Adana Hospital, Seyhan Hospital, Dadaloglu mah. 39 Sk. No 6, 01250 Yuregir, Adana, Turkey.
[Toyganozu, Yavuz] Department of SurgeryAdana, Turkey.
[Bal, Nebil] Baskent University Faculty of Medicine, Department of Pathology, Adana Hospital, Seyhan Hospital, Dadaloglu mah. 39 Sk. No 6, 01250 Yuregir, Adana, Turkey.
[Gursel, Ozgur] Department of GastroenterologyAdana, Turkey.
RP Kayaselcuk, F (reprint author), Baskent University Faculty of Medicine, Department of Pathology, Adana Hospital, Seyhan Hospital, 01250 Yuregir, Adana, Turkey.
EM faziletks@yahoo.com
CR Robey-Cafferty SS, Gringon DJ, Ro JY, et al: Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations. Cancer 65: 1601- 1606, 1990.
Bansal M, Kaneko M, Gordon RE: Carcinosarcoma and separate carcinoid tumor of the stomach. A case report with light and electron microscopic studies. Cancer 50: 1876-1881, 1982.
Fenoglio-Preiser CM, Noffsinger AE, Stemmermann GN, et al: Gastointestinal Pathology. Second ed, 1999; Philadelphia, pp: 262.
Xu LT, Sun CF, Wu LH, et al: Clinical and pathological characteristics of carcinosarcoma of the esophagus: report of four cases. Ann Thorac Surg 37: 197-203, 1984.
Tsuneyama K, Sasaki M, Sabit A, et al: A case report of gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation. Pathol Res Pract 195: 93-97, 1999.
Nakayama Y, Murayama H, Iwasaki H, et al: Gastric carcinosarcoma, sarcomatoid carcinoma, with rhabdomyoblastic and osteoblastic differentiation. Pathol Int 47: 557-563, 1997.
Matsukuma S, Wada R, Hase K, Sakai Y, Ogata S, Kuwabara N: Gastric stump carcinosarcoma with rhabdomyosarcomatous differentiation. Pathol Int 47: 73-77, 1997.
Melato M, Bucconi S, Grillo BP, et al: Carcinosarcoma and separate neuroendocrine malignant tumor of a malignancy promoter, the gastric stump. Anticancer Res 13: 2485-2488, 1993.
Tanimura H, Furuta M: Carcinosarcoma of the stomach. Am J Surg 113: 702-709, 1967.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 275
EP 277
PG 3
ER
PT J
AU Bogner, B
Hegedus, G
AF Bogner, Barna
Hegedus, Geza
TI Ciliated Hepatic Foregut Cyst
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE liver; benign hepatic cysts; ciliated hepatic foregut cyst
ID liver; benign hepatic cysts; ciliated hepatic foregut cyst
AB Ciliated hepatic foregut cyst is a rare, benign, most often solitary and unilocular, rarely multilocular cyst made up of a ciliated pseudostratified columnar epithelium, a subepitheial connective tissue layer, a smooth muscle layer and an outer fibrous capsule. The lesion is usually found incidentally by ultrasonography, during surgical exploration or autopsy. Recent publications characterizes of its fine needle aspiration biopsy features. The lesion is mostly asymptomatic, however one case caused portal vein compression and another which showed malignant trasformation through squamous metaplasia which warns to examine these lesions cautiously. As the lesion is extremely rare it is difficult to estimate its prevalence and its nature, so every single case presentation could be important.
C1 [Bogner, Barna] County Hospital of Baranya, Department of Pathology, Rakoczi ut 2, 7623 Pecs, Hungary.
[Hegedus, Geza] County Hospital of Baranya, Department of Pathology, Rakoczi ut 2, 7623 Pecs, Hungary.
RP Bogner, B (reprint author), County Hospital of Baranya, Department of Pathology, 7623 Pecs, Hungary.
EM bognerb@pathodg.hu
CR Friedrich N: Cyste mit flimmerepithel in der Leber. Archiv Pathol Anat 11: 466-469, 1857.
Hornstein A, Batts KP, Linz LJ et al:Fine needle aspiration diagnosis of ciliated hepatic foregut cysts: a report of three cases. Acta Cytol 40: 576-580, 1996.
Kimura A, Makuuchi M, Takayashu K, et al: Ciliated hepatic foregut cyst with soild tumor appearance on CT. J Comput Assist Tomogr 14: 1016-1018, 1990.
Kadoya M, Matsui O, Nakamuna Y et al: Ciliated hepatic foregut cyst: radiologic features. Radiology 175: 475-477, 1990.
Vick DJ, Goodman ZD, Deavers MT et al.: Ciliated hepatic foergut cyst. Am J Surg Pathol 23: 671-677, 1999.
Vick DJ, Goodman ZD, Ishak KG: Squamous cell carcinoma arising in a ciliated hepatic foregut cyst. Arch Pathol Lab Med 11: 1115-1117, 1999.
Wheeler DA, Edmondson HA.: Ciliated hepatic foregut cyst. Am J Surg Pathol 8: 467-70, 1984.
Zaman SS, Langer JE, Gupta PK: Report of a case with findings on fine needle aspiration. Acta Cytol 39: 781-78 1995.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 278
EP 279
PG 2
ER
PT J
AU Culhaci, N
Levi, E
Sen, S
Kacar, F
Meteoglu, I
AF Culhaci, Nil
Levi, Edi
Sen, Serdar
Kacar, Furuzan
Meteoglu, Ibrahim
TI Pulmonary Lymphomatoid Granulomatosis Evolving to Large Cell Lymphoma in the Skin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE lymphomatoid granulomatosis; Epstein-Barr virus; large cell lymphoma; angiocentric lymphoma
ID lymphomatoid granulomatosis; Epstein-Barr virus; large cell lymphoma; angiocentric lymphoma
AB Lymphomatoid granulomatosis is an angiodestructive, angioinvasive lymphoproliferative disorder. It involves most frequently lungs, central nervous system and skin. Recent studies indicate that lymphomatoid granulomatosis is an Epstein-Barr virus associated B cell disorder with a background of reactive T lymphocytes. In a 49 year old woman presenting with fever, malaise and pulmonary masses the diagnosis of lymphomatoid granulomatosis was established histologically by open lung biopsy. Following the initial diagnosis the patient was found to have gastric and skin involvement. The skin lesion was diagnosed as diffuse large B-cell lymphoma.
C1 [Culhaci, Nil] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Levi, Edi] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Sen, Serdar] Adnan Menderes University, Faculty of Medicine, Department of Thoracic SurgeryAydin, Turkey.
[Kacar, Furuzan] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Meteoglu, Ibrahim] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
RP Culhaci, N (reprint author), Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
EM nculhaci@hotmail.com
CR Patchefsky AS: Nonneoplastic pulmonary disease. In: Sternberg SS, ed). Diagnostic surgical pathology, third ed. Philadelphia: Lippincott Williams&Wilkins pp 1035-1037, 1999
Jaffe ES, Wilson WH: Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 30: 233-247, 1997
Wilson WH, Kingma D, Raffeld M, et al: Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-2b. Blood 87: 4531- 4537, 1996
Kingma D, Fishback N, Wallberg K, et al: Pulmonary lymphomatoid granulomatosis. Evidence for a proliferation of Epstein-Barr virus infected B-lymphocytes with a prominent Tcell component and vasculitis. Am J Surg Pathol 18: 753-764, 1994
Karnak I, Ciftci AO, Talim B, et al: Pulmonary lymphomatoid granulomatosis in a 4 year old. J Pediatr Surg 34: 1033-1035, 1999
Lipford EH, Margolick JB Jr, Longo DL, et al: Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations. Blood 72: 1674-1681, 1988
Guinee DG, Perkins SL, Travis WD, et al: Proliferation and cellular phenotype in lymphomatoid granulomatosis. Implications of a higher proliferation index in B cells. Am J Surg Pathol 22: 1093-1100, 1998
Taniere Ph, Thivolet-Bejui F, Vitrey D, et al: Lymphomatoid granulomatosis- a report on four cases: evidence for B phenotype of the tumoral cells. Eur Respir J 12: 102-106, 1998
Beaty MW, Toro J, Sorbora L, et al: Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol 25: 1111-1121, 2001
Saxena A, Dyker KM, Angel S, et al: Posttransplant diffuse large B-cell lymphoma of "Lymphomatoid Granulomatosis" type. Virch Arch 441:622-628, 2002
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 280
EP 282
PG 3
ER
PT J
AU Dahiya, S
Kumar, R
Sarkar, Ch
Ralte, MA
Sharma, ChM
AF Dahiya, Sonika
Kumar, Rajiv
Sarkar, Chitra
Ralte, Mercy Angela
Sharma, Chand Mehar
TI Clear Cell Odontogenic Carcinoma: a Diagnostic Dilemma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE clear cell odontogenic tumors; clear cell ameloblastoma; maxilla; young age
ID clear cell odontogenic tumors; clear cell ameloblastoma; maxilla; young age
AB A 26-year-old man presented with a swelling in the right side of face and CT scan revealed a destructive tumor in the right maxilla. Tumor recurred within 5 years of its excision and histopathological examination revealed a clear cell odontogenic carcinoma. The rarity of this tumor, occurrence in maxilla and young age of the patient are some of the rare features which need documentation. The importance of its diagnosis and various differential diagnoses are discussed.
C1 [Dahiya, Sonika] All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
[Kumar, Rajiv] All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
[Ralte, Mercy Angela] All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
[Sharma, Chand Mehar] All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
RP Sharma, ChM (reprint author), All India Institute of Medical Sciences, Departments of Pathology and E.N.T., 110029 New Delhi, India.
EM meharsharma@hotmail.com
CR Kramer IRH, Pindborg JJ, Shear M: WHO histological typing of odontogenic tumors. 2nd Ed. Berlin, Germany; Springer Verlag; 1992
Hansen LS, Eversole LR, Green TL, Powell HS: Clear cell odontogenic tumor- A new histological variant with aggressive potential. Head Neck Surg 8: 115-123, 1985
Waldron CA, Small IA, Silverman H: Clear cell ameloblastoma: An odontogenic carcinoma. J Oral Maxillofac Surg 43: 707- 717, 1985
Mari A, Escutia E, Carrera M, Pericot J: Clear cell ameloblastoma or odontogenic carcinoma. J Cranio Maxillofacial Surg 23: 387-390, 1995
Muramatsu T, Hashimoto S, Inoue T, et al: Clear cell odontogenic carcinoma in the mandible: histochemical and immuno histochemical observations with a review of the literature. J Oral Pathol Med 25: 516-521, 1996
Li TJ, Yu SF, Gao Y, Wang E-B: Clear cell odontogenic carcinoma. A clinicopathological and immunohistochemical study of 5 cases. Arch Pathol Lab Med 125: 1566-1571, 2001
Bang G, Koppang HS, Hansen LS et al: Clear cell odontogenic carcinoma : Report of three cases with pulmonary and lymphnode metastases. J Oral Pathol Med18: 113-118, 1989
Eversole LR, Duffey DC, Powell NB. Clear cell odontogenic carcinoma: A clinicopathological analysis. Arch Otololaryngol Head Neck Surg121: 685-689, 1995.
Fan J, Kubota E, Imamura H, et al:Clear cell odontogenic carcinoma: A case report with massive invasion of neighbouring organs and lymph node metastasis. Oral Surg Oral Med Oral Pathol 74: 768-775, 1992.
Milles M, Doyle JL, Mesa M, Raz S:Clear cell odontogenic carcinoma with lymph node metastasis. Oral Surg Oral Med Oral Pathol 76: 82-89, 1993.
Piatteli A, Sesenna E, Trisi P: Clear cell odontogenic carcinoma: Report of a case with lymph node and pulmonary metastases. Eur J Canc Oral Oncol 30B: 278-280, 1994.
Eversole LR: Malignant epithelial odontogenic tumors. Sem Diag Pathol 16: 317-324, 1999
Muller H, Salootweg P: Clear cell differentiation is an ameloblastoma. J Maxillofac Surg 14: 158-160, 1986
Ng KH, Siar CH: Peripheral ameloblastoma with clear cell differentiation. Oral Surg Oral Med Oral Pathol 70: 210-213, 1999
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2002
VL 8
IS 4
BP 283
EP 285
PG 3
ER
PT J
AU Lengyel, E
Gilde, K
Remenar,
Esik, O
AF Lengyel, Erzsebet
Gilde, Katalin
Remenar, Eva
Esik, Olga
TI Malignant Mucosal Melanoma of the Head and Neck - a Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE head and neck; mucosal melanoma; malignant melanoma; surgery radiotherapy; chemotherapy
ID head and neck; mucosal melanoma; malignant melanoma; surgery radiotherapy; chemotherapy
AB Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half of all mucosal melanomas, occurring mainly in the upper respiratory tract, oral cavity and pharynx. They appear with equal gender distribution and with a peak incidence in the age range 60-80 years. In consequence of their hidden location, they are usually diagnosed in a locoregionally advanced clinical stage, with a rate of 5-48% of regional and 4-14% of distant dissemination. The typical therapeutic approach is surgery, postoperative irradiation and systemic therapy. Local control with either surgery or radiotherapy is frequently (60- 70%) achieved, but the rates of local, regional and distant recurrences are high (50-90%, 20-60% and 30-70%, respectively). The reported 5-year actual survival rates are poor (17-48%), which is attributed mainly to a haematogenous dissemination. These characteristics demonstrate that identification of the precursor lesions and more effective local and systemic approaches are needed to improve the therapeutic results.
C1 [Lengyel, Erzsebet] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Remenar, Eva] National Institute of Oncology, Department of Head and Neck SurgeryBudapest, Hungary.
[Esik, Olga] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
RP Lengyel, E (reprint author), National Institute of Oncology, Center of Radiotherapy, 1122 Budapest, Hungary.
EM homokora2001@yahoo.com
CR Agarwala SS, Atkins MB, Kirkwood JM: Current approaches to advanced and high-risk melanoma. Proc Am Soc Clin Oncol 2000.
Ang KK, Byers RM, Peters LJ, et al: Regional radiotherapy as adjuvant treatment for head and neck malignant melanoma. Arch Otolaryngol Head Neck Surg 116:169-172, 1990.
Banfalvi T, Boldizsar M, Gergye M, et al: Comparison of prognostic significance of serum 5-S-Cysteinyldopa, LDH and S- 100B protein in Stage III-IV malignant melanoma. Pathol Oncol Res 8:183-187, 2002.
Barranco SC, Romsdahl MM, Humphrey RM: The radiation response of human malignant melanoma cells grown in vitro. Cancer Res 31:830-831, 1971.
Barton RT: Mucosal melanomas of the head and neck. Laryngoscope 85:93-99, 1975.
Batsakis JD, Regezi JA, Solomon AR, et al: The pathology of head and neck tumors-part 13: mucosal melanomas. Head Neck Surg 4:404-412, 1982.
Berking C, Schlupen E, Schrader A, et al: Tumor markers in peripheral blood of patients with malignant melanoma: Multimarker RT-PCR versus a luminometric assay for S-100. Arch Dermatol Res 291:479-484, 1999.
Blatchford SJ, Koopman CF, Coulthard SW: Mucosal melanoma of the head and neck. Laryngoscope 96:929- 934,1986.
Brandwein MS, Rothstein A, Lawson W, et al: A clinicopathologic study of 25 cases and literature meta-analysis. Arch Otolaryngol Head Neck Surg 123:290-296, 1997.
Britten CD, Rowinsky EK, Baker SD, et al: A phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies. Clin Cancer Res 5:1629, 1999.
Chang AE, Karnell LH, Menck HR: The National Cancer Data Base Report on cutaneous and noncutaneous melanoma. Cancer 83:1664-1678, 1998.
Chapman PB, Einhorn LH, Meyers ML, et al: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17:2745, 1999.
Chaundhry AP, Hampel A, Gorlin RJ: Primary melanoma of the oral cavity. Cancer 11:923-928, 1958.
Cocconi G, Bella M, Calabresi F, et al: Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. N Engl J Med 327:516, 1992.
Eneroth CM, Lungberg C: Mucosal malignant melanomas of the head and neck. Acta Otolaryngol 80:452-458, 1975.
Falkson CI, Falkson G, Falkson HC:Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol 9:1403, 1991.
Falkson CI, Ibrahim J, Kirkwood JM, et al: Phase III trial of dacarbazine versus dacarbazine with interferon -2b versus dacarbazine with interferon -2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study, E3690). J Clin Oncol 16:1743, 1998.
Freedman HM, DeSanto LW, Devine KD, et al: Malignant melanoma of the nasal cavity and paranasal sinuses. Arch Otolaryngol 97: 322-325, 1973.
Gilligan D, Slevin NJ: Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses. Br J Radiol 64:1147-1150, 1991.
Greco FA, Hainsworth JD: Cancer of unknown primery site. In: Cancer: principles and practice of oncology, Eds.: deVita VT Jr, Hellman S, Rosenberg SA, 6th ed, Lippincott Williams and Wilkins, Philadelphia–Baltimore-New York-London-Buenos Aires-Hong Kong–Sydney-Tokyo, 2001, pp. 2537-2569.
Goldman JA, Lawson W, Zak FG, et al: The presence of melanocytes in human larynx. Laryngoscope 82:824-835, 1972
Gotshalk HC, Tessmer CF, Smith JW: Malignant melanoma of palate. Arch Pathol 30:762, 1940.
Guzzo M, Grandi C, Licitra L, et al: Mucosal malignant melanoma of head and neck: forty-eight cases treated at Instituto Nazionale Tumori of Milan. Eur J Surg Oncol 19:316-319,1993.
Hall EJ. Radiobiology for the radiologists. 5th ed. Philadelphia: Lippincott-Williams and Wilkins, 2000.
Harrison DFN, Lund VJ: Tumors of the upper jaw. Edinburgh, London: Churchill Livingstone, 1993, pp. 332.
Keilholz U, Eggermont AM: The role of interleukin-2 in the management of stage IV melanoma: the EORTC melanoma cooperative group program. Canc J Scient Am 6:S99, 2000.
Kingdom TT, Kaplan MJ: Mucosal melanoma of the nasal cavity and paranasal sinuses. Head Neck 17:184-189, 1995.
Lange JR, Raubitschek AA, Pockaj BA, et al: A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy. J Immunother 12:265, 1992.
Lattanzi SC, Tosteson T, Chertoff J, et al: Dacarbazine,cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow up. Melanoma Res 5:365, 1995.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 7
EP 12
PG 6
ER
PT J
AU De Silva, MCh
Reid, R
AF De Silva, MV Chandu
Reid, Robin
TI Gastrointestinal Stromal Tumors (GIST): C-kit Mutations, CD117 Expression, Differential Diagnosis and Targeted Cancer Therapy with Imatinib
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastrointestinal stromal tumors; c-kit; CD117; imatinib
ID Gastrointestinal stromal tumors; c-kit; CD117; imatinib
AB Gastrointestinal stromal tumors (GISTs) have been recognised as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract. They constitute the majority of gastrointestinal mesenchymal tumors. They are defined and diagnosed by the expression of a protooncogene protein called CD117 detected by immunohistochemistry. It is now believed that GISTs originate from gastrointestinal pacemaker cells known as interstitial cells of Cajal, that control gut motility or from a precursor of these cells. The identification of mutations mostly in exon 11 and to a lesser extent in exons 9 and 13 of the c-kit protooncogene coding for c-kit (CD117) in many GISTs, has resulted in a better understanding of their oncogenic mechanisms.The finding of remarkable antitumor effects of the molecular inhibitor, imatinib (Glivec™ ) in metastatic and inoperable GISTs, has necessitated accurate diagnosis of GISTs and their distinction from other gastrointestinal mesenchymal tumors. To achieve this, pathologists need to be familiar with the spectrum of histological appearances shown by GISTs and have a high index of suspicion for these tumors. This review summarises recent advances in knowledge regarding the histogenesis, pathology, molecular biology, genetics and differential diagnosis of GISTs and the basis for the novel targeted cancer therapy with imatinib.
C1 [De Silva, MV Chandu] Western Infirmary, University Department of Pathology, G11 6NT Glasgow, UK.
[Reid, Robin] Faculty of Medicine, University of Colombo, University Department of PathologyColombo, Sri Lanka.
RP Reid, R (reprint author), Faculty of Medicine, University of Colombo, University Department of Pathology, Colombo, Sri Lanka.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 13
EP 19
PG 7
ER
PT J
AU Ribeiro-Silva, A
Zamzelli Ramalho, NL
Garcia, BS
Zucoloto, S
AF Ribeiro-Silva, Alfredo
Zamzelli Ramalho, N Leandra
Garcia, Britto Sergio
Zucoloto, Sergio
TI Is p63 reliable in detecting microinvasion in ductal carcinoma in situ of the breast?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p63; smooth-muscle actin; ductal carcinoma is situ; microinvasion; breast
ID p63; smooth-muscle actin; ductal carcinoma is situ; microinvasion; breast
AB P63, a p53 homologue, is considered to be a marker of myoepithelial cells in breast tissue. This study was carried out to determine the sensitivity of p63 in detecting myoepithelial cells in DCIS and to compare the results obtained with smooth-muscle actin (1A4) in an attempt to verify the reliability of p63 as a possible marker of microinvasion in breast carcinoma. Fifteen DCIS of the breast were submitted to immunohistochemical analysis with anti-p63 and 1A4 antibodies and to a double immunolabeling study using p63 with 1A4. The double immunolabeling study showed that the same cells positive for p63 were also positive for 1A4. The three cases of DCIS with micro-invasion were negative for p63 and 1A4 in the foci of invasiveness. P63 staining was continuous in five of twelve cases of DCIS without microinvasion, being focal and discontinuous in 6 cases and completely negative in one case. Smooth-muscle actin staining was continuous in nine of twelve cases, including the five cases positive for p63. Smooth-muscle actin was focal and discontinuous in only two cases, which were also discontinuous for p63. The DCIS negative for p63 was also negative for 1A4. In conclusion, our results confirm the data of literature that p63 is a specific marker of myoepithelial cells in breast tissue. However, p63 is not as sensitive as 1A4 in staining myoepithelial cells and lack of p63 expression cannot be used as a reliable marker of invasiveness in ductal carcinoma in situ of the breast.
C1 [Ribeiro-Silva, Alfredo] Sao Paulo University School of Medicine, Department of Pathology, Ribeirao Preto - SP, 14048-900 Sao Paulo, Brazil.
[Zamzelli Ramalho, N Leandra] Sao Paulo University School of Medicine, Department of Pathology, Ribeirao Preto - SP, 14048-900 Sao Paulo, Brazil.
[Garcia, Britto Sergio] Sao Paulo University School of Medicine, Department of Pathology, Ribeirao Preto - SP, 14048-900 Sao Paulo, Brazil.
[Zucoloto, Sergio] Sao Paulo University School of Medicine, Department of Pathology, Ribeirao Preto - SP, 14048-900 Sao Paulo, Brazil.
RP Ribeiro-Silva, A (reprint author), Sao Paulo University School of Medicine, Department of Pathology, 14048-900 Sao Paulo, Brazil.
EM ardsilva@rpa.fmrp.usp.br
CR Barbareschi M, Pecciarini L, Cangi MG, et al.: P63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25: 1054-1060, 2001.
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De Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al: Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 94: 2134-2142, 2002.
Di Como CJ, Urist MJ, Babayan I, et al: P63 expression profiles in human normal and tumor tissues. Clin Cancer Res 8: 494-501, 2002.
Douglas-Jones AG, Gupta SK, Attanoos RL, et al: A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast, DCIS): Correlation with grade of associated invasive carcinoma. Histopathology 29: 397-409, 1996.
Foschini MP, Scarpellini F, Gown AM, et al.: Differential expression of myoepithelial markers in salivary, sweat and mammary glands. Int J Surg Pathol 8: 293-7, 2000.
Hoda SA, Prasad ML, Moore A, et al: Microinvasive carcinoma of the breast: can it be diagnosed reliably and its clinically significant? Histopathology 35: 468-472, 1999.
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Little NA, Jochemsen AG:P63. Int J Biochem Cell Biol 34: 6-9, 2002.
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Reis-Filho JS, Albergaria A, Milanezi F, et al: Naked nuclei revisited: p63 immunoexpression. Diagn Cytopathol 27:135-138, 2002.
Reis-Filho JS, Milanezi F, Amendoeira I, et al: P63 staining of myoepithelial cells in breast fine needle aspirates: a study of its role in differentiating in situ from invasive ductal carcinomas of the breast. J Clin Pathol 55: 936-939, 2002.
Reis-Filho JS, Schmitt FC: Taking advantage of basic research: p63 is a reliable myoepithelial and stem cell marker. Adv Anat Pathol 9: 280-289, 2002.
Signoretti S; Waltregny D, Dilks J, et al: P63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157: 1769-1775, 2000. 190.Silver SA, Tavassoli F: Mammary ductal carcinoma in situ with microinvasion. Cancer 82:2382-2390, 1998. 20. Silverstein MJ, Poller DN, Waisman J, et al.: Prognostic classification of breast ductal carcinoma in situ. The Lancet 345:1154-1157, 1995. 210.Skinner KA, Silverstein MJ: The management of ductal carcinoma in situ of the breast. Endocr Relat Cancer 8: 33-45, 2001. 22. Smith GH, Chepko G: Mammary epithelial stem cells. Microsc Res Tech 52: 190-197, 2001. 23. Yang A, Schweitzer R, Sun D, et al: P63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398: 714-718, 1999.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 20
EP 23
PG 4
ER
PT J
AU Bencsath, M
Blaskovits, A
Borvendeg, J
AF Bencsath, Marta
Blaskovits, Aladar
Borvendeg, Janos
TI Biomolecular Cytokine Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic inflammation; therapy; cytokines; infliximab; etanercept
ID chronic inflammation; therapy; cytokines; infliximab; etanercept
AB As for the chronicity of inflammatory-immune diseases, the medication of them needs to be longterm and thus, quite safe with respect to side effects due to drug actions. Therapy of these diseases includes steroid and non steroid anti-inflammatories given in monotherapy or in combination with cytotoxic antimetabolites. Longterm administration of these active substances cumulate in side effects, not to speak of the probability of developing unresponsiveness to the drug in use. In principle, the earlier the intervention, the better the outcome of medication in therapy. In harmony with this principle, biopharmacology focuses on specific targets in early (acute) phase of inflammatory-immune diseases. One of these targets is the proinflammatory cascade of cytokines (IL1beta, IL6, IL8, IL12, TNFalpha). Among them, the overproduction of tumor necrosis factor (TNFalpha) is suggested to orchestrate and escalate the disease phenotype. Hence, targeting of TNFa may restrict or stop the propagation of pathological reactions. TNFalpha in its excess can be captured at transcription, translation, secretion levels as well as in the extracellular soluble form. This latter approach is supported by clinical records emphasizing the use of recombinant antibodies and soluble receptors in trapping extra amounts of TNFalpha. This review serves as an illustration for the efficacy and safety of infliximab (antibody) and etanercept (soluble receptor) in the example of rheumatoid arthritis (RA).
C1 [Bencsath, Marta] National Institute of Pharmacy, Zrinyi u. 3, 1051 Budapest, Hungary.
[Blaskovits, Aladar] National Institute of Pharmacy, Zrinyi u. 3, 1051 Budapest, Hungary.
[Borvendeg, Janos] National Institute of Pharmacy, Zrinyi u. 3, 1051 Budapest, Hungary.
RP Bencsath, M (reprint author), National Institute of Pharmacy, 1051 Budapest, Hungary.
EM bencsath.marta@ogyi.hu
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Reed JC: Apoptosis-based therapies. Nat Rev Drug Disc 1: 111-121, 2002.
Yung RL: Etanercept Immunex. Curr Opin Investig Drugs 2: 216–221, 2001.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 24
EP 29
PG 6
ER
PT J
AU NG, Y
Husain, I
Waterfall, N
AF NG, Yeung
Husain, Imtiaz
Waterfall, Naeha
TI Diabetes Mellitus and Bladder Cancer - An Epidemiological Relationship?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB An epidemiological association between diabetes mellitus and transitional cell carcinoma of the bladder has been proposed. This study looked retrospectively at 125 patients with transitional cell carcinoma of the bladder as a study group and 80 other hospital patients with conditions not specifically associated with diabetes mellitus as a control group. Diabetic patients had an increased, significant odds ratio for bladder cancer compared with non diabetics even after adjustment for smoking and age [OR: 2.69 p=0.049 (95% CI 1.006-7.194)] A history of smoking OR 2.16 p=0.013 (95% C.I. 1.175-3.964) is a significant independent association with transitional cell carcinoma of the bladder as is age: p=0.001 OR 1.07. We propose potential pathogenic pathways for transitional cell carcinoma of the bladder in diabetic patients based on altered integrin and cadherin distribution in urothelial cells in diabetic patients. A larger study is planned to confirm an association between diabetes mellitus and transitional cell carcinoma of the bladder.
C1 [NG, Yeung] University of Dundee, Department of Surgery and Molecular OncologyDundee, UK.
[Husain, Imtiaz] Bedford General HospitalBedford, UK.
[Waterfall, Naeha] Bedford General HospitalBedford, UK.
RP NG, Y (reprint author), University of Dundee, Department of Surgery and Molecular Oncology, Dundee, UK.
EM y.ng@dundee.ac.uk
CR Kravchik S, Gal R, Cytron S et al: Increased Incidence of Diabetes Mellitus in Patients with TCC of Urinary Bladder. Path Oncol Res 7: 56-59, 2001.
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Jin DK, Fish AJ, Wayner EA et al: Distribution of Integrin Subunits in Human Diabetic Kidneys. J Am Soc Nephrol 7: 2636- 2645, 1996.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 30
EP 31
PG 2
ER
PT J
AU Elek, G
Gyori, S
Toth, B
Pap,
AF Elek, Gabor
Gyori, Sandor
Toth, Bernadett
Pap, Akos
TI Histological Evaluation of Preoperative Biopsies from Ampulla Vateri
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE papilla Vateri; preoperative diagnosis; sampling error; papillectomy; biopsy of Vater papilla; pathohistology; forceps biopsy
ID papilla Vateri; preoperative diagnosis; sampling error; papillectomy; biopsy of Vater papilla; pathohistology; forceps biopsy
AB Frequency of the lesions of the papilla Vateri is increasing in Hungary because of epidemiological reasons. Over two years nearly 300 ampullary endoscopic biopsies were taken in our hospital. In 36 percent of the patients the papillary specimens demonstrated acute or chronic inflammation, in 44 percent adenoma, including 5 percent with severe dysplasia, in 5 percent adenomatous hyperplasia and in 7 percent adenomyosis or other benign tumors (2%) were found. Around 7 percent of the ampullary samples proved to be malignant, but only in 2.6 percent were the malignancy of intraampullary origin. Nearly 25 percent of biopsies were repeated once and 10 percent twice or more. Concordance of endoscopic and pathologic diagnoses was 69 percent on average but it increased to 83 percent after including repeated biopsies. In the adenoma-carcinoma group the concordance was 90 percent. The sensitivity of the pathological diagnosis with forceps biopsy was only 77 percent, but it became at least 86 percent following papillectomy. In order to improve diagnostic reliability more extensive use of papillectomy is proposed with close cooperation between the endoscopist and pathologist.
C1 [Elek, Gabor] Central Railway Hospital and Polyclinic, Department of Pathology, Podmaniczky street 111, 1062 Budapest, Hungary.
[Gyori, Sandor] Central Railway Hospital and Polyclinic, Department of Pathology, Podmaniczky street 111, 1062 Budapest, Hungary.
[Toth, Bernadett] Central Railway Hospital and Polyclinic, Department of Pathology, Podmaniczky street 111, 1062 Budapest, Hungary.
[Pap, Akos] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky street 111, 1062 Budapest, Hungary.
RP Pap, (reprint author), Central Railway Hospital and Polyclinic, Department of Gastroenterology, 1062 Budapest, Hungary.
EM papakos@kkk.sote.hu
CR Albores-Saavedra J, Henson DE, Klimstra DS: Tumors of the Gallbladder, extrahepatic bile ducts, and ampulla of Vater. Atlas of tumor pathology, Third series, Fascicle 27, Washington, 2000, pp 10-19, 44, 149-156, 207-209 and 245-358.
Albores-Saavedra J, Murakata L, Krueger JE, et al: Noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts. Cancer 89: 508-515, 2000.
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Allgaier HP, Schwacha H, Kleinschmidt M, et al: Ampullary hamartoma. Digestion 60: 497-500, 1999.
Avisse C, Flament JB, Delattre JF: Ampulla of Vater. Surgical clinics of North America 80: 201-212, 2000.
Bajtai A, Juhasz L, Lonovics J, et al: The papilla of Vater. Melania Publishing Ltd, Budapest, 1995, pp 16-81.
Balgha V, Topa L, Simon K, et al: A Vater papilla tumoros megbetegedesei. Orv Hetil 138: 1387-1391, 1997.
Beger HG, Treitschke F, Gansauge F, et al: Tumor of the ampulla of Vater. Arch Surg 134: 526-532, 1999.
Benchamiche AM, Jouve JL, Manfredi S, et al: Cancer of the ampulla of Vater: results of a 20-year population based study. Eur J Gastroenterol Hepatol 12: 75-79, 2000.
Berczi L, Bocsi J, Lapis K, et al: Relationship between the survival and the clinicopathological parameters of the patients with tumors in the pancreatic head region. Acta chirurgica Hung 38: 235-241,1999.
Clary BM, Tyler DS, Dematos P, et al: Local anpullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms. Surgery 127: 628-633, 2000.
Gouma DJ, Obertrop H: Centralisation of surgery for periampullary malignancy. Br J Surg 86: 1361-1362, 1999.
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Kimura W, Otsubo K: Incidence, sites of origin, and immunohistochemical and histochemical characteristics of atypical epithelium and minute carcinoma of the papilla of Vater. Cancer 61: 1394-1402, 1988.
Kubo H, Chijiiwa Y, Akahoshi K, et al: Pre-operative staging of ampullary tumours by endoscopic ultrasound. Br J Radiol 72: 443-447, 1999.
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Varsanyi M, Gyokeres T, Burai M, et al: Diagnostic and therapeutic pitfalls of periampullary tumours. Z Gastroenterol 39: 428, 2001.
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Witzigmann H, Mobius Ch, Uhlmann D, et al: Behandlungskonzept von Adenomen der Papilla Vateri. Chirurg 71: 197-201, 2000.
Zhao B, Kimura W, Futakawa N, et al: p53 and p21/ Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater. Am J Gastroenterol 94: 2128-2134, 1999.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 32
EP 41
PG 10
ER
PT J
AU Hortovanyi, E
Illyes, Gy
Kadar, A
AF Hortovanyi, Eszter
Illyes, Gyorgy
Kadar, Anna
TI Early Atherosclerosis and Chlamydia Pneumoniae Infection in the Coronary Arteries
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chlamydia pneumoniae; early; atherosclerosis; hypertrophy
ID chlamydia pneumoniae; early; atherosclerosis; hypertrophy
AB In non-atheromatous segments of coronary arteries a sequence of preatherosclerotic changes was identified which consisted of medial thickening followed by intimal thickening. More recently, Chlamydia pneumoniae seropositivity was associated with enhanced intima-media thickness of arteries. In the present study the intimal and medial thickness of coronary artery of young adults were measured, and were correlated with the presence of Chlamydia pneumoniae antigens. Proximal and distal segments of the left anterior descending coronaries (LAD) obtained at autopsy from young adults (15-34 years) were studied. The thickness and cellular density of the intima and of the media without clear-cut atherosclerotic changes were measured by image analysis. The hypertrophy index was calculated as the ratio of cell density and the thickness of the respective layer. Atherosclerotic lesions occurring elsewhere in the same coronary were noted and graded by severity. The presence of Chlamydia pneumoniae verified by immunohistochemistry was correlated with the severity of lesions and with the hypertrophy index. In the proximal segments, atherosclerosis of LAD was associated with the widening of both the intima and the media of lesion free-sites. In the distal coronary segments the proportion of the intimal thickening had a significant association with atherosclerosis. Compared to non-infected arteries, Chlamydia pneumoniae infection was associated with higher hypertrophy index in the intima as well as in the media. The rate of Chlamydia pneumoniae positivity increased with the severity of lesions. As a conclusion: in the LAD coronary, the intimal thickening is the main preatherosclerotic change. Chlamydia pneumoniae may favour arterial wall hypertrophy and plays a role in lesion progression.
C1 [Hortovanyi, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Illyes, Gyorgy] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Kadar, Anna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
RP Kadar, A (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM kadann@korb2.sote.hu
CR Berger M, Schroder B, Daeschlein G, Schneider Wet al.: Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and circulating leukocytes. J Lab Clin Med 136: 194- 200, 2000.
Davidson M, Kuo CC, Middaugh J et al.: Confirmed previous infection with Chlamydia pneumoniae, TWAR, and its presence in early coronary atherosclerosis. Circulation 98: 628-33, 1998.
Gurfinkel E, Bozovich G, Darcoca A et al.: Randomized trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 350: 404-7, 1997.
Ericson K, Saldeen TG, Lindquist O et al.: Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis. Circulation 101: 2568-71, 2000.
Espinola-Klein C, Rupprecht HJ, Blankenberg S et al.: Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? Stroke 31:2127-33, 2000.
Hortovanyi E, Illyes Gy, Glasz T, Kadar A: Chlamydia pneumoniae in different coronary artery segments in the young. Pathol Res Pract 198: 19-23, 2002.
Kadar A., Mozes G, Illyes G et al.: Histomorphometry and histochemistry of atherosclerotic lesions in coronary arteries and the aorta in young population. World Health Organization, WHO, and the World Heart Federation, WHF, Pathobiological Determinants of Atherosclerosis in Youth Study, WHO/WHF PBDAY Study, 1986-1996. Nutr Metab Cardivasc Dis 9:220-227, 1999.
Kuo CC, Grayston JT, Campbell LA et al.: Chlamydia pneumoniae, TWAR, in coronary arteries of young adults, 15-34 years old, Proc Natl Acad Sci USA 92: 6911-14, 1995.
Mayr M, Kiechl S, Willeit Jet al.: Associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and Cytomegalovirus with immune reactions to Heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation 102:833-39, 2000
Molestina RE, Dean D, Miller RD et al.: Characterization of a strain of Chlamydia pneumoniae isolated from a coronary atheroma by analysis of the omp1 gene and biological activity in human endothelial cells. Infect Immun 66:1370-6, 1998,
Ross R: Atherosclerosis – an inflammatory disease. N Engl J Med 340: 115-25, 1999.
Stary HC: Composition and classification of human atherosclerotic lesions. Virchows-Archiv-A-Pathol-Anat 421:277, 1992.
Stary HC: The Histological classification of atherosclerotic lesions in human coronary arteries. Atherosclerosis and Coronary Artery Disease Chapter 26 pp 463-474. Lippincott-Raven Publishers, Philadelphia, 1996.
Tracy RE: Medial thickness of coronary arteries as a correlate of atherosclerosis. Atherosclerosis 139:11-19. 1998.
Tracy RE: Medial thickenings of coronary artery and the aging risk factor for atherosclerosis. Atherosclerosis 155: 337–346, 2001.
Vehmaan-Kreula P, Puolakkainen M, Sarvas M et al.: Chlamydia pneumoniae proteins induce secretion of the 92-kDa gelatinase by human monocyte-derived macrophages. Arterioscler Thromb Vasc Biol 21:1-8, 2001.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 42
EP 46
PG 5
ER
PT J
AU Pecorella, I
Lucas, BS
Ciardi, A
Memeo, L
Miller, FR
AF Pecorella, Irene
Lucas, B Sebastian
Ciardi, Antonio
Memeo, Lorenzo
Miller, F Robert
TI Calcium Oxalate Precipitates in a Renomedullary Interstitial Cell Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE calcium oxalate; kidney; renomedullary interstitial cell tumor
ID calcium oxalate; kidney; renomedullary interstitial cell tumor
AB We report a case of calcium oxalate deposition in a renomedullary interstitial cell tumor (RICT) in a patient dying of full-blown AIDS. The precipitates showed birefringence using a partially polaris ed light and were stained black in Yasue’s silver nitrate-rubeanic acid method. The combination of calcium oxalosis and RICT has not been reported before and might possibly be due to systemic biochemical alterations of the glycosaminoglycans as a result of profound metabolic disturbances in AIDS patients.
C1 [Pecorella, Irene] Universita degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, Viale Regina Elena, 324, 00161 Rome, Italy.
[Lucas, B Sebastian] Guy's Kings and St Thomas's School of Medicine, St Thomas's Hospital, Department of HistopathologyLondon, UK.
[Ciardi, Antonio] Universita degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, Viale Regina Elena, 324, 00161 Rome, Italy.
[Memeo, Lorenzo] Universita degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, Viale Regina Elena, 324, 00161 Rome, Italy.
[Miller, F Robert] Windeyer Institute of Medical Sciences, Royal Free and University College Medical School and Camden and Islington Community Health Services Trust, Department of Sexually Transmitted DiseasesLondon, UK.
RP Pecorella, I (reprint author), Universita degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, 00161 Rome, Italy.
EM irenepecorella@virgilio.it
CR Chaplin AJ. Histopathological occurrence and characterisation of calcium oxalate: a review. J Clin Pathol 30: 800-811, 1977.
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Memeo L, Pecorella I, Ciardi A,et al: Calcium oxalate microdeposition in failing kidney grafts. Transpl Proc 33: 1262-1265, 2001.
Pecorella I, McCartney ACE, Lucas S, et al: Histological study of oxalosis in the eye and adnexa of AIDS patients. Histopathology 27: 431-438, 1995.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 47
EP 48
PG 2
ER
PT J
AU Timar, J
Ladanyi, A
Petak, I
Jeney, A
Kopper, L
AF Timar, Jozsef
Ladanyi, Andrea
Petak, Istvan
Jeney, Andras
Kopper, Laszlo
TI Molecular Pathology of Tumor Metastasis III.
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE metastasis therapy; molecular target; cancer cell; host cell
ID metastasis therapy; molecular target; cancer cell; host cell
AB Therapy of tumor progression and the metastatic disease is the biggest challenge of clinical oncology. Discovery of the diverse molecular pathways behind this complex disease outlined an approach to better treatment strategies. The development of combined cytotoxic treatment protocols has produced promising results but no breakthrough in the clinical management of metastatic disease. The multiple - specific and non-specific pathways and cellular targets of tumor progression are outlined in this review. Such an approach, individually designed for various cancer types, may have a better chance to treat or even cure cancer patients with progressive disease.
C1 [Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Ladanyi, Andrea] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Petak, Istvan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, 1122 Budapest, Hungary.
CR Timar J, Csuka O, Orosz Zs et al: Molecular pathology of tumor metastasis. I. Predictive Pathology. Pathol Oncol Res 7: 217-230, 2001.
Timar J, Csuka O, Orosz Zs et al: Molecular pathology of tumor metastasis. II. Molecular staging and differential diagnosis. Pathol Oncol Res 8: 204-219, 2002.
Thierry JP: Epithelial mesenchymal transitions in tumor progression. Nature Rev Cancer 2: 442-454, 2002.
Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nature Rev Cancer 2: 563-572, 2002.
Ramaswamy S, Ross KN, Golub TR: A molecular signature of metastasis in primary tumors. Nature Genetics 33: 1-6, 2003.
Fidler IJ and Kripke ML: Metastasis results from pre-existing variant cells within a malignant tumor. Science 197:893-895, 1977.
Liotta A and Kohn EC: The microenvironment of the tumorhost interface. Nature 411:375-379, 2001.
Braun et al: Cytokeratin positive cells in the bone marrow and survival of patiens with stage I, II, or III breast cancer. N England J Med 329:257-263, 2000.
Hood JD and Cheresh DA: Role of integrins in cell invasion and migration. Nature Rev Cancer 2: 91-100, 2002.
Yamamoto Y, Tsutsumi Y, Mayumi T: Molecular design of bioconjugated cell adhesion peptide with a water-soluble polymeric modifier for enhancement of antimetastatic effect. Curr Drug Targets 3:123-130, 2002.
Buerkle MA, Pahernik SA, Sutter A et al: Inhibition of the alpha-nu integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo. Br J Cancer 86: 788-795, 2002.
Yi M and Ruoslahti E: A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. PNAS 98: 620-624, 2001.
Trikha M, De Clerck YA, Markland FS: Contortrostatin, a snake venom disintegrin, inhibits beta 1 integrin-mediated human metastatic melanoma cell adhesion and blocks experimental metastasis. Cancer Res 54: 4993-4998, 1994.
Zhou Q, Sherwin RP, Parrish C et al: Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix inhibits breast cancer progression. Breast Cancer Res Treat 61: 249- 260, 2000.
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Ritter MR, Zhou Q, Markland FS Jr: Contortrostatin, a homodimeric disintegrin, actively disrupts focal adhesion and cytoskeletal structure and inhibits cell motility through a novel mechanism. Cell Commun Adhes 8: 71-86, 2001.
Gutheil JC, Campbell TN, Pierce PR et al: Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 30: 3056-3061, 2000.
Cohen SA, Trikha M, Mascelli MA: Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications. Pathol Oncol Res 6: 163-174, 2000.
Trikha M, Zhou Z, Timar J, et al: Multiple roles for platelet GPIIb/IIIa and avb3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res 62: 2824-2833, 2002.
Chen YO, Trikha M, Gao X, et al.: Ectopic expression of platelet integrin aIIibb3 in tumor cells from various species and histological origin. Int J Cancer 72: 642-648, 1997.
Damiano JS: Integrins ad novel drug targets for overcoming innate drug resistance. Current Cancer Drug Targets 2: 37-43, 2002.
Favoni RE, de Cupis A: The role of polypeptide growth factors in human carcinomas: New targets for a novel pharmacological approach. Pharmacol Rev 52: 179-206, 2000.
Zugmaier G, Lippman ME, Wellstein A:Inhibition by pentosan polysulfate, PRS, of heparin-binding growth factors relased from tumor cells and blockage by PRS of tumor growth in animals. J Natl Cancer Res 84: 1716-1724, 1992.
Timar J, Dome B, Fazekas K et al: Angiogenesis-dependent diseases and angiogenesis therapy. Pathol Oncol Res 7: 85-94, 2001.
Baselga J: Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 7: 2-8, 2002.
Shak S, and the Herceptin Multinational Investigator Study Group: Overview of the trastuzumab, Herceptin, anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Semin Oncol 26: 71-77, 1999.
Sliwkowski MX, Lofgren JA, Lewis GD et al: Nonclinical studies addressing the mechanism of action of trastuzumab, Herceptin). Semin Oncol 26(Suppl 12): 60-70, 1999.
Herbst RS, Hong WK: IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer. Semin Oncol 29(Suppl 14): 18-30, 2002.
Huang SM, Li J, Harari PM: Molecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade. Mol Cancer Ther 1: 507-514, 2002.
Fazekas K, Csuka O, Koves I et al: Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis. Clin Exp Metast 18: 639-649, 2001.
Maehara N, Nagai E, Mizumoto K et al: Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer. Clin Exp Metast 19: 417- 426, 2002.
Saimura M, Nagai E, Mizumoto K et al: Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4. Clin Cancer Res 8: 3243-3249, 2002.
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Thurner B, Haendle I, Roder C, et al: Vaccination with Mage- 3A1 peptide-pulsed mature monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 190:1669-1678, 1999. 202. Holtl L, Zelle-Rieser C, Gander H, et al: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8:3369-3376, 2002. 203. Jefford M, Maraskovsky E, Cebon J, et al: The use of dendritic cells in cancer therapy. Lancet Oncol 2:343-353, 2001. 204. Murphy GP, Tjoa BA, Simmons SJ, et al: Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate 38:73-78, 1999. 205. Kugler A, Stuhler G, Walden P, et al: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. 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Bhattathiri VN: Cumulative interfraction interval analysis of influence of time and interruptions on radiotherapy result in oral cancers. Int J Radiat Oncol Biol Phys 52: 1251-1256, 2002.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2003
VL 9
IS 1
BP 49
EP 72
PG 24
ER
PT J
AU Nishimura, Y
Itoh, K
Yoshioka, K
Tokuda, K
Himeno, M
AF Nishimura, Yukio
Itoh, Kazuyuki
Yoshioka, Kiyoko
Tokuda, Kazuo
Himeno, Masaru
TI Overexpression of ROCK in Human Breast Cancer Cells: Evidence that ROCK Activity Mediates Intracellular Membrane Traffic of Lysosomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ROCK; RhoA; Cathepsin D; LIMPII; lysosomes; endosomes; cytoskeleton
ID ROCK; RhoA; Cathepsin D; LIMPII; lysosomes; endosomes; cytoskeleton
AB Small GTPase Rho and its downstream effectors, ROCK family of Rho-associated serine-threonine kinases, are thought to participate in cell morphology, motility, and tumor progression through regulating the rearrangement of actin cytoskeleton. Here we present evidence that transfection of human breast cancer cells with cDNA encoding a dominant active mutant of ROCK causes dispersal of lysosomal vesicles throughout the cytoplasm without perturbing the machinery of the endocytic pathway. The intracellular distribution of lysosomes and endocytosed transferrin, an early endosomal marker, were further assessed by confocal immunofluorescence microscopy. In the active ROCK transfected cells the lysosomal proteins, cathepsin D, LIMPII, and LAMP1, were found throughout the cytoplasm in dispersed small vesicles, which were accessible to the endocytosed Texas Red-labeled transferrin. 3D-image analysis of lysosomal distribution in the active ROCKtransfectants revealed abundant punctate signals in the peripheral region of the basal plasma membrane. Cells expressing vector alone did not exhibit these alterations. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, induced LIMPII-positive/ transferrin negative large vacuoles in the perinuclear region, and disappearence of the dispersed small vesicular structures. To our knowledge, this is the first evidence that increasing ROCK expression contributes to selective cellular dispersion of lysosomes in invasive breast cancer cells.
C1 [Nishimura, Yukio] Kyushu University, Faculty of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
[Itoh, Kazuyuki] Osaka Medical Center for Cancer and Cardiovascular Diseases, Research InstituteOsaka, Japan.
[Yoshioka, Kiyoko] Osaka Medical Center for Cancer and Cardiovascular Diseases, Research InstituteOsaka, Japan.
[Tokuda, Kazuo] Kyushu University, Faculty of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
[Himeno, Masaru] Kyushu University, Faculty of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
RP Nishimura, Y (reprint author), Kyushu University, Faculty of Pharmaceutical Sciences, 812-8582 Fukuoka, Japan.
EM nishimur@bioc.phar.kyushu-u.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 83
EP 95
PG 13
ER
PT J
AU Raso, E
Paku, S
Kopper, L
Timar, J
AF Raso, Erzsebet
Paku, Sandor
Kopper, Laszlo
Timar, Jozsef
TI Trace Elements Improve Survival of DTIC-Treated Mice with Overt Liver Metastases of Lewis Lung Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 3LL-HH tumor; mice; trace element mixture; liver metastasis; survival; 5-FU; DTIC
ID 3LL-HH tumor; mice; trace element mixture; liver metastasis; survival; 5-FU; DTIC
AB Trace elements have been previously shown to have specific antimetastatic effects in a mouse 3LLHH liver metastasis model. Here we have analyzed the effect on the survival of animals with liver metastases. Trace elements administered per os at 500-5000 mg/kg/day did not affect the survival of animals with liver metastases. However, when trace element treatment was combined with dacarbazine (DTIC) administration, the survival of animals was significantly improved (55%). This effect was specific for DTIC since trace elements did not influence the effect of 5-fluorouracil on survival in this liver metastasis model. These data and those found in the literature all suggest that trace elements can specifically modulate the antitumoral/antimetastatic effects of chemotherapeutic agents.
C1 [Raso, Erzsebet] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy 7-9, H-1122 Budapest, Hungary.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy 7-9, H-1122 Budapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, H-1122 Budapest, Hungary.
CR Gal K, Bertok L: The effect of X-radiation on reticuloendothelial system and its treatment with radiotoxified endotoxin and trace elements in rats. Acta Microbiol Immunol Hung 41: 457-463, 1994
Falus A, Beres J Jr: A trace element preparation containing zinc increases the production of interleukon-6 in human monocytes and glial cells. Trace Element Res 51: 293-301, 1996
Grinevich JA, Beres J. Jr, Bendyug GD: A trace element preparation increases antitumor activity in mice. Pathol Oncol Res 3: 34-37, 1997
Timar J, Raso E, Paku S , Kopper L: Oral administration of a trace element preparation and zinc inhibit liver metastasis of 3LL-HH murine tumor cells. Int J Molec Med 2: 105-108, 1998
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Satoh M, Nagamura A, Imura N: Modulation of adriamycin toxicity by tissue-specific induction of metallothionein synthesis in mice. Life Sci 67:627-634, 2000
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Katano K, Kondo A, Safaei R et al:Acquisition of resistance to cisplatin is accompanied by changes in the extracellular pharmacology of copper. Cancer Res 62:6559-6565, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 96
EP 99
PG 4
ER
PT J
AU Cengiz-Boduroglu, E
Irkkan,
Bilir, G
AF Cengiz-Boduroglu, Esin
Irkkan, Cigdem
Bilir, Gulay
TI Is Nothingham Prognostic Index Correlated with Apoptosis and P53 Expression in Infiltrating Ductal Carcinoma of the Breast?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; apoptosis; disease free survival; prognostic index
ID p53; apoptosis; disease free survival; prognostic index
AB The role of p53 as a prognostic factor is not clear. P53 named as ''guardian of the genome” plays an important role in many intracellular regulatory systems, one of which is apoptosis, having an impact on tumor kinetics. A retrospective study was undertaken to assess the relationship of the Nothingham Prognostic Index (NPI) to p53 expression and apoptotic cell counts. To conduct the study, 160 successive cases of infiltrating ductal carcinoma of the breast were included. P53 was assessed on AP-AAP stained sections. Apoptotic cell counting (ACC) was done on the HE stained routine sections in 10 HPFs. Clinical data were derived from the hospital files. Apoptotic cell counts were higher in the p53 positive group but the difference was not significant (p=0.079). P53 positivity was found to be related to the disease-free survival (DFS) (p=0.008). NPI was significantly higher in apoptotic cell containing group (p=0.006). There was a positive linear correlation between ACC and NPI scores (p=0.004). This correlation was not present between apoptosis and disease free survival. P53 expression was found to be related with DFS but not with the NPI which is a score composed of the best prognostic indicators known today. In contrast to this, ACC was found to be closely and linearly associated to the known prognostic factors. This may suggest that the apoptotic cell counts done on routine sections may be used as a part of prognosis assessment in infiltrating ductal carcinoma.
C1 [Cengiz-Boduroglu, Esin] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of Pathology, Ortadogu Camlik Sitesi No: 88 Karakusunlar, 06530 Ankara, Turkey.
[Irkkan, Cigdem] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of Pathology, Ortadogu Camlik Sitesi No: 88 Karakusunlar, 06530 Ankara, Turkey.
[Bilir, Gulay] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of Pathology, Ortadogu Camlik Sitesi No: 88 Karakusunlar, 06530 Ankara, Turkey.
RP Cengiz-Boduroglu, E (reprint author), Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of Pathology, 06530 Ankara, Turkey.
EM ebodur@ada.net.tr
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Gonzales-Campora R, Galera Ruiz MR, Vasquez RF, et al.: Apoptosis in breast carcinoma. Pathol Res Pract 196: 167-174, 2000
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 100
EP 103
PG 4
ER
PT J
AU Szomor,
Zenou, P
Roda, D
Al Saati, T
Csanaky, Gy
Pajor, L
Kelenyi, G
Delsol, G
Losonczy, H
AF Szomor, Arpad
Zenou, Prune
Roda, Daniel
Al Saati, Talal
Csanaky, Gyorgy
Pajor, Laszlo
Kelenyi, Gabor
Delsol, Georges
Losonczy, Hajna
TI Genotypic Analysis in Primary Systemic Anaplastic Large cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE anaplastic large cell lymphoma; TCR g- and bgene rearrangement; IgH gene rearrangement; t(2; 5)(p23; q35) and t(1; 2)(q25; p23) translocation
ID anaplastic large cell lymphoma; TCR g- and bgene rearrangement; IgH gene rearrangement; t(2; 5)(p23; q35) and t(1; 2)(q25; p23) translocation
AB This report presents an experience of polymerase chain reaction (PCR) analysis of T-cell receptor g- and bgene (TCR g, TCR b), and immunoglobulin heavy chain (IgH) gene rearrangements in 9 cases of primary systemic anaplastic large cell lymphoma. We showed 2 clonal IgH, 2 TCR g, 1 TCR b rearrangements. The genotype was B/T-cell in 1, T-cell in 1, B-cell in 1 and null cell-type in 6 cases. We used reverse transcriptase PCR (RT-PCR) to detect t(2;5)(p23;q35) and t(1;2)(q25;p23) translocations. T(2;5) translocation was demonstrated in 2 cases, there was no t(1;2) translocation. In most cases the molecular genetic results were found to be in agreement with immunophenotypic data.
C1 [Szomor, Arpad] University of Pecs, I. Department of Internal Medicine, Ifjusag u.13., 7624 Pecs, Hungary.
[Zenou, Prune] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Roda, Daniel] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Al Saati, Talal] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Csanaky, Gyorgy] Markusovszky Hospital, Department of PathologySzombathely, Hungary.
[Pajor, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Kelenyi, Gabor] University of Pecs, Department of PathologyPecs, Hungary.
[Delsol, Georges] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Losonczy, Hajna] University of Pecs, I. Department of Internal Medicine, Ifjusag u.13., 7624 Pecs, Hungary.
RP Szomor, (reprint author), University of Pecs, I. Department of Internal Medicine, 7624 Pecs, Hungary.
EM aszomor@clinics.pote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 104
EP 106
PG 3
ER
PT J
AU Kurup, KR
Nair, AR
Kurup, AP
AF Kurup, Kumar Ravi
Nair, A Rekha
Kurup, Achutha Parameswara
TI Isoprenoid Pathway Related Cascade in Multiple Myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE digoxin; dolichol; ubiquinone; multiple myeloma
ID digoxin; dolichol; ubiquinone; multiple myeloma
AB This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in multiple myeloma. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+ - K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, nicotine, strychnine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins, cholesterol and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of lipid peroxidation products and NO increased. Hyperdigoxinemia related altered intracellular Ca++ mediated oncogene activation, dolichol induced altered glycoconjugate metabolism and ubiquinone deficiency related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical findings reported could be the cause or the consequence of multiple myeloma.
C1 [Kurup, Kumar Ravi] Medical College Hospital, Department of NeurologyKerala, India.
[Nair, A Rekha] Regional Cancer Center, II. Department of PathologyKerala, India.
[Kurup, Achutha Parameswara] Metabolic Disorders Research Center, Gouri Sadan, T.C.4/1525, North of Cliff House, Kattu Road, Kowdiar P.O., TrivandrumKerala, India.
RP Kurup, AP (reprint author), Metabolic Disorders Research Center, Kerala, India.
EM kvgnair@satyam.net.in
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 107
EP 114
PG 8
ER
PT J
AU Esik, O
Csere, T
Stefanits, K
Lengyel, Zs
Safrany, G
Vonoczky, K
Lengyel, E
Nemeskeri, Cs
Repa, I
Tron, L
AF Esik, Olga
Csere, Tibor
Stefanits, Klara
Lengyel, Zsolt
Safrany, Geza
Vonoczky, Katalin
Lengyel, Erzsebet
Nemeskeri, Csaba
Repa, Imre
Tron, Lajos
TI A Review on Radiogenic Lhermitte's Sign
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiation myelopathy; permanent Lhermitte's sign; magnetic resonance imaging; positron emission tomography; [18F]fluorodeoxyglucose; [15O]butanol; [11C]methionine
ID radiation myelopathy; permanent Lhermitte's sign; magnetic resonance imaging; positron emission tomography; [18F]fluorodeoxyglucose; [15O]butanol; [11C]methionine
AB Radiation myelopathy is a rare, but extremely serious side-effect of radiotherapy. Recovery from radiation-induced motor sequelae is rare, whereas, the regeneration of sensory losses is relatively frequent. Among the sensory radiogenic injuries of the spinal cord, Lhermitte's sign (LS) is most frequent. This review describes the clinical picture and diagnostic imaging signs of radiogenic LS. There have been only a few studies on large patient groups with radiogenic LS, demonstrating a rate of occurrence of 3.6-13%, relating mainly to mantle irradiation or the radiotherapy of head and neck tumors. These cases typically manifest themselves 3 months following radiotherapy and gradually disappear within 6 months. Only 3 LS cases have been described in the English literature with extraordinarily severe symptoms lasting for more than 1 year. MRI, a sensitive tool in the detection of demyelination, failed to reveal any pathological sign accompanying radiogenic LS. However, positron emission tomography demonstrated increased [18F]fluorodeoxyglucose accumulation and [15O]butanol perfusion, but a negligible [11C]methionine uptake in the irradiated spinal cord segments in patients with long-standing LS. These imaging data are suggestive of a close direct relationship between the regional perfusion and metabolism of the spinal cord, very much like the situation in the brain. We postulate that an altered, energy-demanding conduction along the demyelinated axons of patients with chronic radiogenic LS may explain the increased metabolism and perfusion.
C1 [Esik, Olga] Semmelweis University, Department of Oncology, Rath Gyorgy u 7-9, H-1122 Budapest, Hungary.
[Csere, Tibor] University of Pecs, Department of OncologyPecs, Hungary.
[Stefanits, Klara] University of Pecs, Department of OncologyPecs, Hungary.
[Lengyel, Zsolt] University of Debrecen, PET CenterDebrecen, Hungary.
[Safrany, Geza] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato IntezetBudapest, Hungary.
[Vonoczky, Katalin] National Institute of Oncology, Outpatient Department of NeurologyBudapest, Hungary.
[Lengyel, Erzsebet] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Nemeskeri, Csaba] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Repa, Imre] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Tron, Lajos] University of Debrecen, PET CenterDebrecen, Hungary.
RP Esik, O (reprint author), Semmelweis University, Department of Oncology, H-1122 Budapest, Hungary.
EM esik@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 115
EP 120
PG 6
ER
PT J
AU Farjadian, Sh
Asadi, E
Doroudchi, M
Samsami Dehaghani, A
Tabei, S
Kumar, VP
Ghaderi, A
AF Farjadian, Shirin
Asadi, E
Doroudchi, Mehrnoosh
Samsami Dehaghani, Alamtaj
Tabei, Z. Seyed
Kumar, Vijayananda Perikala
Ghaderi, Abbas
TI High Risk HPV Types in Southern Iranian Patients with Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical cancer; HPV
ID cervical cancer; HPV
AB This study was undertaken to assess the rate of HPV infection in cervical carcinoma among southern Iranian patients. 101 archival cervical carcinoma tissue samples of a 10 year period were studied for the presence of HPV DNA in southern Iran by a polymerase chain reaction method. In addition, the presence of high risk HPV-16 and HPV-18 genotypes was investigated. In total, 88 (87.1%) of the samples were HPV DNA positive, of which 83 were squamous cell carcinomas and 5 were adenocarcinomas. HPV-16 genotype was detected in 26.7% of HPV positive cervical carcinomas; however, none of the samples were positive for the existence of HPV-18 genotype. Collectively, these results suggest that HPV-16 and HPV-18 are not the frequent high risk HPV types in our patients and circulating HPV types in southern Iranian population are different from many other populations.
C1 [Farjadian, Shirin] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Asadi, E] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Doroudchi, Mehrnoosh] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Samsami Dehaghani, Alamtaj] Shiraz University of Medical Sciences, Department of Obstetrics and GynecologyShiraz, Iran.
[Tabei, Z. Seyed] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Kumar, Vijayananda Perikala] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Ghaderi, A (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM ghaderia@sums.ac.ir
CR Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2:533-543, 2001
Farahmandbeigi M, Kadivar MR: The incidence rate of registered cancer in Fars province. Disease Control Unit, Shiraz University Press, Iran, 2000
Bosch FX, Munoz N. The viral etiology of cervical cancer. Virus Res 89:183-190, 2002
Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12-19, 1999
Southern SA, Herrington CS. Disruption of cell cycle control by human papillomaviruses with special reference to cervical carcinoma. Int J Gynecol Cancer 10:263-274, 2000
Park TW, Fujiwara H, Wright TC. Molecular biology of cervical cancer and its precursors. Cancer 76:1902-1913, 1995
IARC working Group, Human papilloma viruses, IARC Monograph on the evaluation of carcinogenic risks to humans. Lyon, France: International Agency for Research on Cancer, 65, 1995
Badaracco G, Venuti A, Sedati A, Marcante ML. HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol 67:574-582, 2002
Munoz N, Franceschi S, Bosetti C, et al. International Agency for Research on Cancer. Multicentric Cervical Cancer Study Group Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study.Lancet 359:1093-1101, 2002
Castle PE, Wacholder S, Lorincz AT, et al.A prospective study of high-grade cervical neoplasia risk among human papillomavirusinfected women. J Natl Cancer Inst 94:1406-1414, 2002
Rong S, Chen W, Wu L, et al. Analysis of risk factors for cervical cancer in Xiangyuan County, Shanxi Province Zhonghua Yu Fang Yi Xue Za Zhi 36:41-43, 2002
Mandelblatt JS, Lawrence WF, Womack SM, et al. Benefits and costs of using HPV testing to screen for cervical cancer. JAMA 287:2372-2381, 2002
Castellsague X, Menendez C, Loscertales MP, et al. Human papillomavirus genotypes in rural Mozambique. Lancet 358:1429-1430, 2001
Snijders PJ, van den Brule AJ, Schrijnemakers HF, et al. The use of general primers in the polymerase chain reaction permits the detection of a broad spectrum of human papillomavirus genotypes. J Gen Virol 71:173-181, 1990
Samoylova EV, Shaikhaiev GO, Petrov SV, et al. HPV infection in cervical cancer cases in Russia. Int J Cancer 61:337-341, 1995
Ferenczy A, Franco E. Cervical-cancer screening beyond the year 2000. Lancet Oncol 2:27-32, 2002
Sebbelov AM, Davidson M, Kruger Kjaer S, et al. Comparison of human papillomavirus genotypes in archival cervical cancer specimens from Alaska natives, Greenland natives and Danish Caucasians. Microbes Infect 2:121-126, 2000
Goncalves MA, Massad E, Burattini MN, Villa LL. Relationship between human papillomavirus, HPV, genotyping and genital neoplasia in HIV-positive patients of Santos City, Sao Paulo, Brazil. Int J STD AIDS 10:803-807, 1999
Lo KW, Wong YF, Chan MK, et al. Prevalence of human papillomavirus in cervical cancer: a multicenter study in China. Int J Cancer 100:327-331, 2002
Baay MF, Tjalma WA, Weyler J, et al. Human papillomavirus infection in the female population of Antwerp, Belgium: prevalence in healthy women, women with premalignant lesions and cervical cancer. Eur J Gynaecol Oncol 22:204-208, 2001
Chen S, O’Sullivan H, Tabrizi SN, et al. Prevalence and genotyping of HPV in cervical cancer among Australian women. Int J Gynaecol Obstet 67:163-168, 1999
Chabaud M, Le Cann P, Mayelo V, et al. Detection by PCR of human papillomavirus genotypes in cervical lesions of Senegalese women. J Med Virol 49:259-263, 1996
Beskow AH, Gyllensten UB. Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri. Int J Cancer 101:526-531, 2002
Zwaveling S, Ferreira Mota SC, Nouta J, et al. Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J Immunol 169:350-358, 2002
Dehaghani AS, Amirzargar A, Farjadian S, Ghaderi A. HLADQBl alleles and susceptibility to cervical squamous cell carcinoma in Southern Iranian patients. Pathol Oncol Res 8:58- 61, 2002
Amirzargar A, Mytilineos J, Farjadian Sh, et al. Human Leukocyte Antigen class II allele frequencies and haplotype association in Iranian population. Hum Immunol 62:1234- 1238, 2001
Hording U, Teglbjaerg CS, Visfeldt J, Bock JE. Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix. Gynecol Oncol 46:313-316, 1992
Bjersing L, Rogo K, Evander M, et al. HPV 18 and cervical adenocarcinomas. Anticancer Res 11:123-127, 1991
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 121
EP 125
PG 5
ER
PT J
AU Otto, Sz
AF Otto, Szabolcs
TI Cancer Epidemiology in Hungary and the Bela Johan National Program for the Decade of Health
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer epidemiology; Hungary; morbidity; mortality
ID cancer epidemiology; Hungary; morbidity; mortality
AB According to a recent survey, in 1995 Hungary lead cancer mortality statistics in men in Europe, while was on the second place in the case of women. The figures for cancer morbidity were highly similar. According to cancer types, the Hungarian mortality rates are the worst in the case of lung, oral cavity laryngeal and pancreatic cancers among men and oral cavity colorectal and thyroid cancers in women. Between 1999 and 2001 in Hungary the cancer mortality list is topped by lung and colorectal cancers among men and by breast and colorectal cancers among women. The National Cancer Registry started to provide reliable morbidity data which indicate that in 2001 in Hungary the men's most frequent cancer types are lung, colorectal and lip and mouth cancers while among women breast, colorectal and lung cancers. These shocking cancer mortality and morbidity figures outlined the primary targets of the recently lunched national public health program for this decade.
C1 [Otto, Szabolcs] National Institute of Oncology, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
RP Otto, Sz (reprint author), National Institute of Oncology, H-1122 Budapest, Hungary.
EM sz.otto@oncol.hu
CR Andersen RE. Healthy people 2010. Phys Sportsmed 28: 7-8, 2000
Bray F, Sankila R, Ferlay J, Parkin DM. Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer 38:99- 166, 2002
Demografiai evkonyvek KSH, Volumes of the Demographical Yearbook, KSH – Central Statistics Office, Budapest 1975- 2000 in Hungary,, in Hungarian)
Public Health Program “For a Healthy Population” 2001-2010. Target Program for the Prevention of Public Health Problem. Egeszsegugyi Kozlony, Health Bulletin in Hungary, 51:2237- 2322, 2001, in Hungarian)
Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer Statistics, 2001. CA Cancer J Clin 51:15-36, 2001
Otto S, Schumann B: Planning and development of tumormarker examinations. Lege Artis Med 9:114-117, 1999, in Hungarian)
Otto S, Kasler M: Cancer mortality and Incidence in Hungary in relation to international data. Hungarian Oncol 46:111-117, 2002, in Hungarian)
Jozan P: The basic trend of mortality in the 20th century and mortality conditions at the turn of the millennium in Hungary. Hungarian Science 4:419-439, 2002, in Hungarian)
Dobrossy L: Cancer mortality in central-eastern Europe: facts behind the figures. Lancet Oncol 3:374-381, 2002
Kopp MS, Skrabski A and Szedmak S: Psychosocial risk factors, inequality and self-rated morbidity in a changing society. Soc Sci Med 51: 1351-1361, 2000
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 126
EP 130
PG 5
ER
PT J
AU Gopcsa, L
Barta, A
Banyai, A
Dolgos, J
Halm, G
Paloczi, K
AF Gopcsa, Laszlo
Barta, Aniko
Banyai, Aniko
Dolgos, Janos
Halm, Gabriella
Paloczi, Katalin
TI Salvage Chemotherapy with Donor Lymphocyte Infusion and STI 571 In a Patient Relapsing with B-Lymphoblastic Phase Chronic Myeloid Leukemia after Allogeneic Bone Marrow Transplantation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE CML; blastic phase; allogeneic HSCT; DLI; STI 571
ID CML; blastic phase; allogeneic HSCT; DLI; STI 571
AB Relapse is the main cause of treatment failure following hematopoietic stem cell transplantation for blastic phase chronic myeloid leukemia. Treatment options including donor lymphocyte infusion, second transplantation, interferon- and re-induction chemotherapy are often unsuccessful. We report a patient with blastic phase chronic myeloid leukemia relapsing after allogeneic stem cell transplantation. The post-transplant leukemia was characterized with B-lymphoid markers and multiple genetic abnormalities including double Ph-chromosomes. The disease was treated with three courses of salvage chemotherapy combined with donor lymphocyte infusion and bcr-abl tyrosine kinase inhibitor. The leukemia proved to be non-responsive both to immune therapy and STI 571. The presented case demonstrates the need for combination approaches in post-transplant relapsed leukemia and discusses the possible contributing mechanisms of STI-571 resistance.
C1 [Gopcsa, Laszlo] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
[Barta, Aniko] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
[Banyai, Aniko] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
[Dolgos, Janos] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
[Halm, Gabriella] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
[Paloczi, Katalin] National Medical Center, Department of Immunology, H-1519 Budapest, Hungary.
RP Gopcsa, L (reprint author), National Medical Center, H-1519 Budapest, Hungary.
EM k.paloczi@ohvi.hu
CR Baron F, Frere P, Fillet G et al: Treatment of leukaemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI 571, Haematologica 86: 993-994, 2001
Carlens S, Remberger M, Aschan I et al: The role of disease stage in the response to donor lymphocyte infusions as treatment for leukemic relapse. Biol Blood Marrow Transplant 7: 31-38, 2001
Druker BJ, Sawyers CL, Kantarjian H et al: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. New Engl J Med 344:1038- 1042, 2001
Elmaagacli AH, Beelen DW and Schaefer UW: A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 20: 1045-1055, 1997
Gopcsa L, Barta A, Banyai A et al: Acute myeloid leukaemia of donor cell origin developing five years after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transplant 29:449-452, 2002
Kantarjian H, Melo JV, Tura S et al: Chronic myelogenous leukemia: disease biology and current and future therapeutic strategies. Hematology, Am Soc Hematol Educ Program, 90- 109, 2000
Mughal TI and Goldman JM: Chronic myeloid leukaemia: STI 571 magnifies the therapeutic dilemma. Eur J Cancer 37:561- 568, 2001
Thomas ED and Clift RA: Allogeneic transplantation for chronic myeloid leukemia. In: Hematopoietic cell transplantation., Eds: Thomas ED, Blume KG and Forman SJ, Blackwell Scientific Publications, Malden, 1999, pp. 807-816
Visani G, Rosti G, Bandini G et al: Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia. Br J Haematol 109: 722-728, 2000
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 131
EP 133
PG 3
ER
PT J
AU Halbauer, JD
Meszaros, I
Doczi, T
Kajtar, P
Pajor, L
Kovacs, K
Gomori,
AF Halbauer, J D
Meszaros, Istvan
Doczi, Tamas
Kajtar, Pal
Pajor, Laszlo
Kovacs, Krisztina
Gomori, Eva
TI Rare Sellar Region Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE intracranial midline tumor; pituitary adenoma; granular cell tumor; germinoma
ID intracranial midline tumor; pituitary adenoma; granular cell tumor; germinoma
AB We present three cases of rare intracranial midline tumor in the sellar region, often mimiking pituitary adenomas clinically. We describe their symptoms, radiological and pathomorphological features. The first case is a pituitary adenoma producing growth hormone with ganglion cell differentiation. In addition, a rare intracranial granular cell tumor of sellar region and germinoma of pituitary fossa are also presented. All tumors were resected and histologically analyzed. Their biological behaviour was favorable with a 10-year follow-up demonstrating no recurrent tumor mass.
C1 [Halbauer, J D] University of Pecs, Department of Pathology, 12. Szigeti u., H- 7643 Pecs, Hungary.
[Meszaros, Istvan] Pecsi Tudomanyegyetem, Idegsebeszeti KlinikaPecs, Hungary.
[Doczi, Tamas] Pecsi Tudomanyegyetem, Idegsebeszeti KlinikaPecs, Hungary.
[Kajtar, Pal] University of Pecs, Department of PediatricsPecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, 12. Szigeti u., H- 7643 Pecs, Hungary.
[Kovacs, Krisztina] University of Pecs, Department of Pathology, 12. Szigeti u., H- 7643 Pecs, Hungary.
[Gomori, Eva] University of Pecs, Department of Pathology, 12. Szigeti u., H- 7643 Pecs, Hungary.
RP Gomori, (reprint author), University of Pecs, Department of Pathology, H- 7643 Pecs, Hungary.
EM geva@pathology.pote.hu
CR Albrecht S, Armstrong DL, Mahoney DH et al: Cytogenetic demonstration of gene amplification in a primary intracranial germ cell tumor. Genes Chromosome Cancer 6: 61-63, 1993.
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Barrande G, Kujas M, Gancel A et al: Granular cell tumors. Rare tumors of the neurohypophysis. Press Med 24: 1676-1680, 1995.
Becker DH, Wilson CB: Symptomatic parasellar granular cell tumors. Neurosurgery 8: 173-179, 1981.
Dickson DV, Suzuki KI, Kanner R et al: Cerebral granular cell tumor: immunohistochemical and electron microscopic study. J Neuropathol Exp Neurol 45: 304-314, 1986.
Geddes JF, Jansen GH, Robinson SFD et al: Gangliocytoma of the pituitary: a heterogeneous group of lesions with differing histogenesis. Am J Surg Path 24: 607-613, 2000.
Giangaspero F, Cennachi G: Oncocytic and granular cell neoplasms of the central nervous system and pituitary gland. Semin Diagn Pathol 16: 91-97, 1999.
Gomori E, Halbauer DJ, Doczi T et al: Cytogenetic profile of primary pituitary germinoma. J Neuro-Oncol 50: 251-255, 2000.
Horvath E, Kovacs K, Scheithauer BW et al: Pituitary adenoma with neuronal choristoma, PANCH): composite lesion or lineage infidelity? Ultrastruct Pathol 18: 565-574, 1994.
Iwase T, Nishizawa S, Baba S: Intrasellar neuronal choristoma associated with growth hormone-producing pituitary adenoma containing amyloid deposits. Hum Pathol 26: 925-928, 1995.
Kohler L: Case of the month. April 1996-pituitary tumor. Brain Pathol 6: 531-532, 1996.
Matsutani M, Sano K, Takakura K et al: Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86: 446-455, 1997.
Nakashima T, Nishimura Y, Sakai N et al: Germinoma in cerebral hemisphere associated with Down syndrome. Childs Nerv Syst 13: 563-566, 1997.
Puchner MJ, Ludecke DK, Saeger W et al: Gangliocytomas of the sellar region – a rewiev. Exp Clin Endocrinol Diabetes 103: 129-149, 1995.
Rickert CH, Kuchelmeister K, Gillotta F: Morphological and immunohistochemical characterisation of granular cell in nonhypophyseal tumors of the central nervous system. Histopathology 30: 464-471, 1997.
Sainati L, Bolcato S, Montaldi A et al: Cytogenetics of pediatric central nervous system tumors. Cancer Genet Cytogenet 91: 13-27, 1996.
Tomita T, Gates E: Pituitary adenoma and granular cell tumor. Incidence, cell type and location of tumor in 100 pituitary glands at autopsy. Am J Clin Pathol 111: 817-825, 1999.
Towfighi J, Salam MM, McLendon RE et al:Ganglion cell-containing tumors of the pituitary gland. Arch Pathol Lab Med 120: 369-377, 1996.
Wong TT, Ho DM, Chang TK et al: Familial neurofibromatosis 1 with germinoma involving the basal ganglion and thalamus. Childs Nerv Syst 11: 456-458, 1995.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2003
VL 9
IS 2
BP 134
EP 137
PG 4
ER
PT J
AU Marchetti, D
Denkins, Y
Reiland, J
Greiter-Wilke, A
Galjour, J
Murry, B
Blust, J
Roy, M
AF Marchetti, Dario
Denkins, Yvonne
Reiland, Jane
Greiter-Wilke, Andrea
Galjour, Jennifer
Murry, Brian
Blust, Jason
Roy, Madhuchhanda
TI Brain-Metastatic Melanoma: a Neurotrophic Perspective
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE brain metastasis; malignant melanoma; neurotrophins; neurotrophin receptors; p75NTR; heparanase; astrocytes
ID brain metastasis; malignant melanoma; neurotrophins; neurotrophin receptors; p75NTR; heparanase; astrocytes
AB The brain is a unique microenvironment enclosed by the skull and maintaining a highly regulated vascular transport barrier. To metastasize to the brain, malignant tumor cells must attach to microvessel endothelial cells, invade the blood-brain barrier (BBB), and respond to brain survival and growth factors. Neurotrophins (NT) are important in brain invasion because they stimulate this process. In brain-metastatic melanoma cells, NT can promote invasion by enhancing the production of extracellular matrixdegradative enzymes such as heparanase, an enzyme capable of locally destroying both the extracellular matrix and the basement membrane of the BBB. We have examined human and murine melanoma cell lines exhibiting varying abilities to form brain metastases, and have found that they express low-affinity neurotrophin receptor p75NTR in relation to their brain-metastatic potentials. They do not, however, express trkA, the gene encoding the tyrosine kinase receptor TrkA, the high-affinity receptor for nerve growth factor (NGF), the prototypic NT. Presence of functional TrkC, the putative receptor for the invasion-promoting neurotrophin NT-3, was also expressed in these cells. Brain-metastatic melanoma cells can also produce autocrine factors and inhibitors that influence their growth, invasion, and survival in the brain. Synthesis of these factors may influence NT production by brain cells adjacent to the neoplastic invasion front, such as oligodendrocytes and astrocytes. In brain biopsies, we observed increased amounts of NGF and NT-3 in tumor-adjacent tissues at the invasion front of human melanoma tumors. Additionally, we found that astrocytes contribute to the brain-metastatic specificity of melanoma cells by producing NT-regulated heparanase. Trophic, autocrine, and paracrine growth factors may therefore determine whether metastatic cells can successfully invade, colonize, and grow in the central nervous system (CNS).
C1 [Marchetti, Dario] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Denkins, Yvonne] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Reiland, Jane] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Greiter-Wilke, Andrea] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Galjour, Jennifer] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Murry, Brian] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Blust, Jason] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
[Roy, Madhuchhanda] Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, Skip Bertman Drive, LA 70803 Baton Rouge, USA.
RP Marchetti, D (reprint author), Louisiana State University School of Veterinary Medicine, Department of Comparative Biomedical Sciences, LA 70803 Baton Rouge, USA.
EM dmarchetti@vetmed.lsu.edu
CR Prados M, Wilson C: Neoplasms of the central nervous system. In: Holland, J.F., Frei, III.E., Bast, Jr.R.C., Kufe, D.W., Morton, D.L., Weischselbaum, R.R., Eds.), Cancer Medicine. Philadelphia: Lea & Febiger, pp. 1080-1119, 1993.
Sawaya R, Ligon, BL, Bindal, AK, et al.: Surgical treatment of metastatic brain tumors. J. Neurooncol 27: 269-277, 1996.
Soffietti R, Ruda, R, and Mutani, R. Management of brain metastases. J Neurol. 249: 1357-1369, 2002.
Steck, P, and Nicolson G: Metastasis to the central nervous system. In: Levine, A., Schmidek, H., Eds.), Molecular Genetics of Nervous System Tumors. New York: Wiley and Sons, pp. 371-379, 1993
Fidler IJ: The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nature Rew Cancer 3: 1-6, 2003.
Nicolson GL, Menter DG, Herrmann, JL, et al.: Brain metastasis: role of trophic, autocrine, and paracrine factors in tumor invasion and colonization of the central nervous system. Curr Top Microbiol Immunol 213: 89-115, 1996.
Yano S, Shinohara H, Herbst RS, et al.: Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 60: 4959-4967, 2000.
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Raff MC, Barres BA, Burne, JF, et al.: Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262: 695-700, 1993.
Snider WD: Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627-638, 1994.
Jones KR, Farinas I, Backus C, and Reichardt LF: Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76: 989-999, 1994.
DiCicco-Bloom E, Friedman, WJ, and Black IB: NT-3 stimulates sympathetic neuroblast proliferation by promoting precursor survival. Neuron 11: 1101-1111, 1993.
Chao MV, and Bothwell M: Neurotrophins: to cleave or not to cleave. Neuron 33: 9-12, 2002.
Johnson D, Lanahan, A, Buck, CR, et al.: Expression and structure of the human NGF receptor. Cell 47: 545-554, 1986.
Maher PA: Nerve growth factor induces protein-tyrosine phosphorylation. Proc Natl Acad Sci U.S.A. 85: 6788-6791, 1988.
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Ohmichi M, Decker SJ, and Saltiel AR: Nerve growth factor stimulates the tyrosine phosphorylation of a 38-kDa protein that specifically associates with the src homology domain of phospholipase C-gamma 1. J Biol Chem 267:21601-21606, 1992.
Barbacid M: Nerve growth factor: a tale of two receptors. Oncogene 8: 2033-2042, 1993.
Chao MV: Neurotrophins and their receptors: a convergence point for many signalling pathways. Nature Rev 4: 299-309, 2003.
Meakin SO, and Shooter EM: The nerve growth factor family of receptors. Trends Neurosci 15: 323-331, 1992.
Saltiel AR, and Decker SJ: Cellular mechanisms of signal transduction for neurotrophins. Bioassays 16: 405-411, 1994.
Birren SJ, Lo L, and Anderson DJ: Sympathetic neuroblasts undergo a developmental switch in trophic dependence. Development 119: 597-610, 1993.
Kalcheim C, Carmeli C, and Rosenthal A: Neurotrophin-3 is a mitogen for cultured neural crest cells. Proc Natl Acad Sci U.S.A. 89: 1661-1665, 1992.
Schnell L, Schneider R, Kolbeck R, et al.: Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 367: 170-173, 1994.
Ernfors P, Lee KF, Kucera J, and Jaenisch R: Lack of neurotrophin- 3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77: 503- 512, 1994.
Klein R, Silos-Santiago I, Smeyne RJ, et al.: Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature 368:249-251, 1994.
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Marchetti D, Murry B, Galjour J, and Wilke-Greiter A: Human melanoma TrkC: Its association with a purine-analogsensitive kinase activity. J Cell Biochem 88: 865-872, 2003.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 147
EP 158
PG 12
ER
PT J
AU Makar, RR
Saji, T
Junaid, T
AF Makar, Ray Ragai
Saji, Tessy
Junaid, A. Tola
TI Epstein-Barr Virus Expression in Hodgkin's Lymphoma in Kuwait
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hodgkin's lymphoma; Epstein Barr virus; in situ hybridization; Epstein Barr virus encoded RNA; immunohistochemistry; Epstein Barr virus latent membrane protein 1
ID Hodgkin's lymphoma; Epstein Barr virus; in situ hybridization; Epstein Barr virus encoded RNA; immunohistochemistry; Epstein Barr virus latent membrane protein 1
AB The epidemiology of Hodgkin's lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein-Barr virus (EBV). The proportion of EBV positive HL is low in industrialized countries, high in non-industrialized countries and intermediate in early-industrialized countries. Reports from the Persian Gulf and Middle East are very limited. The aim of this study was to determine the epidemiology of HL in Kuwait, an early-industrialized country in the Persian Gulf, and to delineate the extent of its association with EBV. We reviewed 134 cases of HL for histological classification and demographic data. 107 cases were examined for the presence of EBV using immunohistochemistry (IHC) for the latent membrane protein I (LMPI) and in-situ hybridization (ISH) for EBVencoded RNA (EBER). 70.4% of the patients were males and 29.6% were females. The male: female ratio was 2.4:1. The mean age was 30.6 years (range, 4-71 years). Mixed cellularity HL (MCHL) was the most common subtype (45.5%), followed by nodular sclerosis (37.3%), nodular lymphocyte predominant (6.7%), lymphocyte rich (3%) and lymphocyte depletion (3%). 4.5% of cases were unclassifiable. EBV expression was seen in 56%, was significantly higher in MCHL, in children, and in males. Our findings suggest that the frequency of EBV expression in HL in Kuwait is similar to other early-industrialized countries. Further research from other countries in the Persian Gulf and the Middle East should shed more light on the epidemiology of HL and its relation to EBV in this region.
C1 [Makar, Ray Ragai] Faculty of Medicine, Kuwait University, Department of Pathology, 1330 SW Third Avenue #1210, OR 97201 Portland, OR, USA.
[Saji, Tessy] Faculty of Medicine, Kuwait University, Department of Pathology, 1330 SW Third Avenue #1210, OR 97201 Portland, OR, USA.
[Junaid, A. Tola] Faculty of Medicine, Kuwait University, Department of Pathology, 1330 SW Third Avenue #1210, OR 97201 Portland, OR, USA.
RP Makar, RR (reprint author), Faculty of Medicine, Kuwait University, Department of Pathology, OR 97201 Portland, USA.
EM rosymakar@aol.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 159
EP 165
PG 7
ER
PT J
AU Boer, K
Lang, I
Juhos,
Pinter, T
Szanto, J
AF Boer, Katalin
Lang, Istvan
Juhos, Eva
Pinter, Tamas
Szanto, Janos
TI Adjuvant Therapy of Breast Cancer with Docetaxel-Containing Combination (TAC)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE early breast cancer; adjuvant chemotherapy; comparative study; docetaxel
ID early breast cancer; adjuvant chemotherapy; comparative study; docetaxel
AB The adjuvant chemotherapy of breast cancer changed in the past two decades. Docetaxel containing regimens are highly active in metastatic breast cancer. A logical approach was their incorporation into trials of early breast cancer adjuvant therapy. The authors present the Hungarian interim analysis and experience with the BCIRG 001 randomized, multicentric, phase III clinical trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) and FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer patients. The results are presented compared to the international data. Three Hungarian centers - Szt. Margit Hospital, Budapest, National Institute of Oncology, Budapest, Petz Aladar Hospital, Gyor - participated in the international trial. Between June 1997 and June 1999, 61 patients with node positive breast cancer were enrolled in the study after the surgery. Thirty-four patients were randomized to TAC (75/50/500 mg/m2 6xq3wk) and 27 patients were randomized to FAC (500/50/500 mg/m2 6x q3wk) chemotherapy, with prospective stratification by node (1-3, 4+). Patients with hormone receptor positive tumors received tamoxifen for 5 years after the chemotherapy. Radiotherapy was performed after the 6th cycle of chemotherapy. 33 months of follow up was performed. In both arms the hematological toxicity was more frequent. The TAC group showed a higher incidence of neutropenia (76%) compared to the FAC (22%), as well as a higher incidence of febrile neutropenia (26 % versus none), without grade 3-4 infection and there was no cases of septic death. More grade 3-4 nausea and vomiting was observed in the FAC group. At three years follow up, results indicated improvement in disease-free survival (88% vs. 76%) in favour of TAC, and similar tendency was observed in the case of overall survival (97% vs. 88%). Based on the international data analysis TAC was superior to FAC chemotherapy, the results show statistically significant differences between the two arms. This benefit with TAC was seen regardless of hormone receptor status. Additional follow up data will evaluate the role of TAC in the adjuvant setting of early breast cancer treatment.
C1 [Boer, Katalin] Szent Margit Hospital, V. Department of Internal Medicine - Oncology, Becsi ut 132, H-1032 Budapest, Hungary.
[Lang, Istvan] National Institute of OncologyBudapest, Hungary.
[Juhos, Eva] National Institute of OncologyBudapest, Hungary.
[Pinter, Tamas] Petz Aladar County HospitalGyor, Hungary.
[Szanto, Janos] Szent Margit Hospital, V. Department of Internal Medicine - Oncology, Becsi ut 132, H-1032 Budapest, Hungary.
RP Boer, K (reprint author), Szent Margit Hospital, V. Department of Internal Medicine - Oncology, H-1032 Budapest, Hungary.
EM kboer@freemail.hu
CR Amadori D, Nanni O, Marangolo M et al: Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-negative rapidly proliferating breast cancer. A randomized multicenter study. J Clin Oncol 18: 3125-3134, 2000
Baki M, Rado J, Gyergyay F es mtsai: Tapasztalataink elorehaladott stadiumu emlodaganatos betegek Adriblastin, A, es Docetaxel, D, osszehasonlito vizsgalata soran. Magy Onkol Tars XXII. Nemzeti Kongr Magyar Onkol 41: 300-301, 1997, in Hungarian)
Bonadonna G, Valagussa P: The contribution of medicine to the primary treatment of breast cancer. Cancer Res 48: 2314- 2324, 1998
Bonneterre, Roche H, Monnier A et al: Taxotere(TXT, versus 5-Fluorouracil + Navelbine, FUN, as second-line chemotherapy, CT, in patients, pts, with metastatic breast cancer, MBC). Proc Am Soc Clin Oncol 16:162a, 1997
Chan S, Friedrich K, Noel D et al: Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 17: 2341-2354, 1999
Early Breast Cancer Trialists Collaborative Group: Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet. 352: 930-942, 1998
Early Breast Cancer Trialists Collaborative Group: 2000 analysis overview results. Fifth Meeting of the Early Breast Cancer Trialists Collaborative Group, Oxford, United Kingdom, September 21-23, 2000
Early Breast Cancer Trialists Collaborative Group: Tamoxifen for early breast cancer : an overview of the randomized trials. Lancet 351:1451-1507, 1998
Eckhardt S: A docetaxel hatasa a daganatokra. Orv Hetilap 139: 867-872, 1998, in Hungarian)
Fumoleau P, Chevalier B, Kerbrat P et al: A multicentre phase II study of the efficacy and safety of docetaxel as first –line treatment of advanced breast cancer. A report of the Clinical Screening Group of the EORTC. Ann Oncol 7: 165- 171, 1996
Goldhirsch A, Glick JH, Gelber RD, Senn HJ: Highlights. International consensus panel on treatment of primary breast cancer. J Natl Cancer Inst 90: 1601-1608, 1998
Nabholtz JM, Mackey JR, Smylie M et al: Final results of phase II study of docetaxel, doxorubicin and cyclophosphamide, TAC, as 1st line chemotherapy in metastatic breast cancer patients. Breast Cancer Res Treat 50:227, 1998
Nabholtz JM, Pienkowski T, Mackey J et al: Phase III trial comparing TAC, docetaxel, doxorubicin, cyclophosphamide, with FAC, 5-fluorouracil, doxorubicine, cyclophosphamide, in the adjuvant treatment of node positive breast cancer, BC, patients: interim analysis of the BCIRG 001 study. Proc Am Soc Clin Oncol, abstract No 141, 21: 36a, 2002
Piccart MJ, Lohrisch C, Duchateau L et al: Taxanes in the adjuvant setting: why not yet ? J Natl Cancer Inst Monogr 30: 88-95, 2001
Sjostrom J, Mouridsen H, Pluzanska A et al: Taxotere, T, versus methotrexate-5 fluorouracil, MF, in patients with advanced anthracycline- resistant breast cancer. Proc Am Soc Clin Oncol 17:111a, 1998
Szanto J, Pinter T, Szanto J: Doxorubicin + docetaxel-, illetoleg doxorubicin + cyclophosphamid-kezelessel elerheto eredmenyek tavoli attetet ado emlorakban. Orvosi Hetilap 142; 723-726, 2001, in Hungarian)
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 166
EP 169
PG 4
ER
PT J
AU Wrobel, T
Mazur, G
Surowiak, P
Wolowiec, D
Jelen, M
Kuliczkowsky, K
AF Wrobel, Tomasz
Mazur, Grzegorz
Surowiak, Pawel
Wolowiec, Dariusz
Jelen, Michal
Kuliczkowsky, Kazimierz
TI Increased Expression of Vascular Endothelial Growth Factor (VEGF) in Bone Marrow of Patients with Myeloproliferative Disorders (MPD)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; myeloproliferative disorders; VEGF
ID angiogenesis; myeloproliferative disorders; VEGF
AB Angiogenesis is a multistep process of the development of capillaries from established blood vessels. Angiogenesis probably plays a significant role in the development and progression of hematopoietic malignancies. Higher microvascular density and increased serum levels of proangiogenic factors such as vascular endothelial growth factor (VEGF) or basic fibroblasts growth factor (bFGF) have been reported in acute and chronic leukemias, myeloproliferative and myelodysplastic disorders, multiple myeloma and lymphomas. The microvessel density of bone marrow stroma in myeloproliferative disorders is increased and VEGF is considered as the most potent endothelial cell activator. The purpose of this study was to examine the expression of VEGF in bone marrow of patients with MPD. 60 paraffinembedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated. In addition 10 bone marrow core biopsy specimens from adult patients without evidence of malignancy were used as controls. Bone marrow sections were stained immunohistochemically for VEGF (PharMingen, USA). Obtained data show that MPD are associated with an increased expression of VEGF in the bone marrow. This observation support previous studies suggesting that angiogenesis may play a role in the pathophysiology of myeloproliferative disorders. Clinical significance of this phenomenon needs further investigation however thus provides rationale for use of angiogenesis inhibitors in MPD therapy.
C1 [Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, ul. Pasteura 4, 50-367 Wroclaw, Poland.
[Mazur, Grzegorz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, ul. Pasteura 4, 50-367 Wroclaw, Poland.
[Surowiak, Pawel] Wroclaw Medical University, Department of Human Morphology and EmbryologyWroclaw, Poland.
[Wolowiec, Dariusz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, ul. Pasteura 4, 50-367 Wroclaw, Poland.
[Jelen, Michal] Wroclaw Medical University, Department of PathologyWroclaw, Poland.
[Kuliczkowsky, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, ul. Pasteura 4, 50-367 Wroclaw, Poland.
RP Wrobel, T (reprint author), Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 50-367 Wroclaw, Poland.
EM wrobelt@hemat.am.wroc.pl
CR Belgore FM, Lip G, Bareford D, et al: Plasma levels of vascular endothelial growth factor, VEGF, in haematological cancers. Br J Haematol 110: 496-497, 2000.
Elliot MA, Mesa RA, Li CY, et al: Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol 117: 288-296, 2002.
Faderl S, Talpaz M, Estrov Z, et al: The biology of chronic myeloid leukemia. N Engl J Med 341: 164-172, 1999.
Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27-31, 1995.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 170
EP 173
PG 4
ER
PT J
AU Kereskai, L
Vass, AJ
Kneif, M
Pajor, L
AF Kereskai, Laszlo
Vass, A Janos
Kneif, Maria
Pajor, Laszlo
TI Correlation Between BCR-ABL Expression and Tumor Burden is Restricted to the Transition from Minor to Major Cytogenetic Response in Interferon Treated CML Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic myeloid leukaemia; molecular monitoring; quantitative polymerase chain reaction; fluorescence in situ hybridisation
ID chronic myeloid leukaemia; molecular monitoring; quantitative polymerase chain reaction; fluorescence in situ hybridisation
AB The interferon treatment of chronic myeloid leukaemia has been monitored by investigating the tumour burden as revealed by fluorescence in situ hybridization and the expression of BCR-ABL chimera determined by quantitative reverse transcription polymerase chain reaction. These parameters were obtained from the peripheral blood of 51 untreated and 104 follow-up patient samples. Poor corrrelation (r=0.31) was found between BCR-ABL expression and tumor load in all samples as well as in untreated patients, and this correlation was even less in all follow-up cases (r=0.28). Regarding chimera expression five order of magnitude difference existed in the untreated patients and this value dropped to two in those with complete cytogenetic response. Only the major and the complete cytogenetic response groups differed significantly (p<0.001) in the BCR-ABL expression from that of patients at diagnosis. Among the different cytogenetic response groups the only significant difference (p<0.01) in the BCRABL expression was obtained between the major and the minor responders. In the individual patients not only correlated changes of residual tumour mass and chimera expression, but mainly independent changes of these two parameters were observed. This indicates that the BCR-ABL expression and the tumor burden are largely independent variables.
C1 [Kereskai, Laszlo] University of Pecs, Department of Pathology, 12 Szigeti Str, H-7624 Pecs, Hungary.
[Vass, A Janos] University of Pecs, Department of Pathology, 12 Szigeti Str, H-7624 Pecs, Hungary.
[Kneif, Maria] University of Pecs, Department of Pathology, 12 Szigeti Str, H-7624 Pecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, 12 Szigeti Str, H-7624 Pecs, Hungary.
RP Pajor, L (reprint author), University of Pecs, Department of Pathology, H-7624 Pecs, Hungary.
EM pajor@pathology.pote.hu
CR Bedi A, Zehnbauer BA, Collector MI, et al: BCR-ABL gene rearrangement and expression of primitive hematopoietic progenitors in chronic myeloid leukemia. Blood 81: 2898-2902, 1993
Bentz M, Cabot G, Moos M,et al: Detection of chimeric BCRABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukaemia by in situ hybridization. Blood 83: 1922-1928, 1994
Brizard F, Chomel JC, Veinstein A, et al: Does BCR-ABL genomic rearrangement persist in CML patients in complete remission after interferon therapy? Leukemia 12: 1076-1080, 1998
Cuneo A, Bigoni R, Emmanuel B, et al: Fluorescence in situ hybridization for the detection and monitoring of the Ph-positive clone in chronic myelogenous leukemia: comparison with metaphase banding analysis. Leukemia 12: 1718-1723, 1998
Dewald GW, Schad CR, Christensen ER, et al: The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in variant Ph chromosomes in CML and ALL. Cancer Genet Cytogen 71: 7-14, 1993
Faderl S, Talpaz M, Kantarjian HM, et al: Should polymerase chain reaction analysis to detect minimal residual disease in patients with chronic myelogenous leukemia be used in clinical decision making? Blood 93: 2755-2759, 1999
Furukawa Y, Iwase S: Antileukemic effect of interferon-a is mediated through down-modulation of E2F activity. Leukemia 11: 446-448, 1997
Gaiger A, Henn T, Horth E, et al: Increase of BCR-ABL chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood 86: 2371-2378, 1995
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Pajor L, Vass JA, Kereskai L, et al: Silent Philadelphia chromosome: A distinct developmental stage in a Philadelphia chromosome-positive chronic myeloproliferation? Cancer Genet Cytogen 118: 14-19, 2000
Reiter A, Marley SB, Hochhaus A, et al: BCR-ABL-positive progenitors in chronic myeloid leukaemia patients in complete cytogenetic remission after treatment with interferon-alpha. Brit J Haematol 102: 1271-1278, 1998
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Talpaz M, Kantarjian HM, Kurznock R, et al: Interferon-alfa produces sustained cytogenetic responses in chronic myelogenous leukaemia Ph-chromosome positive patients. Ann Intern Med 114: 532-538, 1991
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Verfaillie CM, Bhatia R, Miller W, et al: BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated- phase chronic myelogenous leukemia patients. Blood 87: 4770-4779, 1996
Yanagi M, Shinjo K, Takeshita A, et al:Simple and reliably sensitive diagnosis and monitoring of Philadelphia chromosomepositive cells in chronic myeloid leukemia by interphase fluorescence in situ hybridization of peripheral blood cells. Leukemia 13: 542-552, 1999
Zhang JG, Lin F, Chase A, et al: Comparison of genomic DNA and cDNA for detection of residual disease after treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation. Blood 87: 2588-2593, 1996
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 174
EP 179
PG 6
ER
PT J
AU Gorog, D
Nagy, P
Peter, A
Perner, F
AF Gorog, Denes
Nagy, Peter
Peter, Antal
Perner, Ferenc
TI Influence of Obesity on Lymph Node Recovery from Rectal Resection Specimens
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE rectal resection; lymph node; obesity
ID rectal resection; lymph node; obesity
AB Careful lymph node dissection from colorectal resection specimens is important procedure for cancer staging. Present study intended to assess the impact of surgical technique and patient’s obesity on this process. Number of lymph nodes harvested by manual dissection from resection specimens of 141 patients with rectal cancer and the rate of nodal metastases were analyzed and compared in different groups of patients selected by length of resection specimen and body mass index. The median and mean number of lymph nodes found per patient were 6 and 6.7. The shorter resection specimens (<16 cm after formalin fixation) yielded significantly lower number of nodes than those with length > 16 cm (5.7 versus 7.9). Most significant reduction in mean number of lymph nodes was observed in obese patients with short specimens (4.8). This subset of patients presented the lowest rate of nodal metastases (38%). The surgical technique seems to be an important factor for lymph node recovery from rectal resections specimens. The patient’s obesity had an unfavourable impact on this procedure. Standardized surgery and histopathological examination are needed even in non-specialized centers to harvest adequate number of lymph nodes.
C1 [Gorog, Denes] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Nagy, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Peter, Antal] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
RP Gorog, D (reprint author), Semmelweis University, Department of Transplantation and Surgery, H-1082 Budapest, Hungary.
EM gorogd@freemail.hu
CR Blenkinsopp WK, Stewart-Brown S, Blesovsky L, et al: Histopathology reporting in large bowel cancer. J Clin Pathol 34: 509-513, 1981
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Cianchi F, Palomba A, Boddi V, et al: Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined. World J Surg 26: 384-389, 2002
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Tepper JE, O’Connel MJ, Niedzwiecki D, et al:Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19: 157-163, 2001
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 180
EP 183
PG 4
ER
PT J
AU Liszkay, G
Peley, G
Sinkovics, I
Peter, I
Orosz, Zs
Fejos, Zs
Horvath, B
Koves, I
Gilde, K
Kasler, M
AF Liszkay, Gabriella
Peley, Gabor
Sinkovics, Istvan
Peter, Ilona
Orosz, Zsolt
Fejos, Zsuzsa
Horvath, Bela
Koves, Istvan
Gilde, Katalin
Kasler, Miklos
TI Clinical Significance of Sentinel Lymph Node Involvement in Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sentinel lymph node; melanoma; prognosis; tumor thickness
ID sentinel lymph node; melanoma; prognosis; tumor thickness
AB In the period 1997-2002, sentinel lymph node (SLN) surgery was performed on 179 primary skin melanoma patients, one to two months after the removal of the primary. Staining with patent blue was combined with an isotope technique. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph node was followed, preferably within 2-3 weeks, by regional block dissection. In these cases interferon-a2 in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14.7%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.00001). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007 respectively). Comparison of the tumor thickness and positive SLN by discriminance analysis, yielded 81.7% and 79.9%, respectively for correct classification rates. Based on our study and data from the literature, we suggest SLN-positivity as equally strong poor prognosis factor for skin melanoma as the tumor thickness.
C1 [Liszkay, Gabriella] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Peley, Gabor] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Sinkovics, Istvan] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Peter, Ilona] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Fejos, Zsuzsa] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Horvath, Bela] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Koves, Istvan] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Kasler, Miklos] National Institute of Oncology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Liszkay, G (reprint author), National Institute of Oncology, H-1122 Budapest, Hungary.
EM liszkay@oncol.hu
CR Alazraki MT, Eshima LA: Lymphoscintigraphy, the sentinel node concept, and the intraoperative gamma probe in melanoma, breast cancer, and other potential cancers. Semin Nucl Med 27: 55-67, 1997
Alex JC, Krag DN: Gamma-probe-guided localization of lymph nodes. Surg Oncol 2: 137-147, 1993
Association od Directors of Anatomic and Surgical Pathology. ADASP recommendations for processing and reporting lymph node specimens submitted for evaluation of metastatic disease. Am J Surg Pathol 25: 961-963, 2001
Buzaid AC, Balch CM: Proposed change of TNM classification. Mel Res 11 Suppl: S4-S5, 2001
Cabanas RM: An approach for the treatment of penile cancer. Cancer 39: 456-466, 1977
Coldiron MB:Sentinel node biopsy: who needs it? Int J of Dermatol 39: 807-811, 2000
Kirkwood JM, Hunt Strawdwrman M, Ernstoff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: The Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14:7-17, 1996
Krag DN, Meijer SJ, Weaver DL, et al: Minimal access surgery for staging of malignant melanoma. Arch Surg 130: 654-658, 1995
Lens MB, Dawes M, Newton-Bishop JA: Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy. Br J Surg 89:1223-1227, 2002
Liszkay G, Peley G, Farkas E, et al. Sentinel node biopsy for melanoma in 103 patients. Early follow-up study. EJSO 28: 357, 2002
Moore MP, Kinne DW. Axillary lymphadenectomy: A diagnostic and therapeutic procedure. J Surg Oncol 66: 2-6, 1997
Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127: 392-399, 1992
Reintgen D, Balch CM, Kirkwood J, et al. Recent advances in the care of the patient with malignant melanoma. Ann Surg 225: 1-14, 1997
Ronan GS, Eng MA, Briele AH, et al. Thin malignant melanomas with regression and metastases. Arch Dermatol 123: 1326- 1330, 1987
Ross MI. Surgical management of stage I and II melanoma patients: approach to the regional lymph node basin. Semin Surg Oncol 12: 394-401, 1996
Ross MI, Reintgen D, Balch Ch: Selective lymphadenectomy: Emerging role of lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. Semin Surg Oncol 9: 219-223, 1993
Starz H, Gerstel C, Bachter D, et al: Two simple morphometric parameters permit a clinically relevant staging of the sentinel node metastases in malignant melanoma and merkel cell carcinoma. Eur J Nucl Med 26, Suppl): S68, 1988
Taylor A, Murray D, Herda S, et al. Dynamic lymphoscintigraphy to identify the sentinel and satellite nodes. Clin Nucl Med 21: 755-758, 1996
Timar J, Csuka O, Orosz Z et al:Molecular pathology of tumor metastasis. II. Molecular staging and differential diagnosis. Pathol Oncol Res 8: 204-219, 2002
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 184
EP 187
PG 4
ER
PT J
AU Mannweiler, S
Dinges, PH
Beham-Schmid, Ch
Hauser, H
Starlinger, M
Regauer, S
AF Mannweiler, Sebastian
Dinges, Peter Hans
Beham-Schmid, Christine
Hauser, Hubert
Starlinger, Michael
Regauer, Sigrid
TI Colliding / Concomitant Tumors of the Intestine: Report of 3 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adenocarcinoma; non-Hodgkin lymphoma; colon; ileum
ID adenocarcinoma; non-Hodgkin lymphoma; colon; ileum
AB Collision/concomitant tumors of the intestine involving lymphomas are very rare. For these cases molecular genetic analyses are valuable diagnostic adjuncts. We report one collision tumor of the rectum (adenocarcinoma and peripheral T-cell lymphoma, unspecified), and two cases of concomitant tumors (carcinoma in the cecum and lymphoma in the ileum; carcinoma in the sigmoid and lymphoma in the ileum). The collision tumor (poorly differentiated adenocarcinoma and a peripheral T-cell lymphoma, unspezified) showed a variable proportion of the anaplastic tumor cells expressing lymphatic markers as well as cytokeratin. Only polymerase chain reaction (PCR) analysis revealing T-cell monoclonality of the anaplastic part of the colliding tumor allowed the correct diagnosis. In the second case, a moderately differentiated adenocarcinoma in the cecum with a concomitant B-cell Non-Hodgkin lymphoma in the ileum, PCR analysis was non contributary. In the third case (adenocarcinoma in the sigmoid colon and a follicular center lymphoma in the ileum) PCR analysis revealed gene rearrangement of the immunoglobulin heavy chain gene. We would like to emphasize that collision and concomitant tumors of the gut are rare and that molecular genetic analysis may be mandatory for correct diagnosis. It is our impression, that these tumors may be diagnosed more often in the intestinal tract if molecular genetic analysis and immunohistochemistry are used routinely, at least for all anaplastic tumors.
C1 [Mannweiler, Sebastian] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Dinges, Peter Hans] Hospital Klagenfurt, Department of PathologyKlagenfurt, Austria.
[Beham-Schmid, Christine] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Hauser, Hubert] University of Graz, Surgical DepartmentGraz, Austria.
[Starlinger, Michael] Landeskrankenhaus Klagenfurt, Surgical DepartmentKlagenfurt, Austria.
[Regauer, Sigrid] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
RP Mannweiler, S (reprint author), Medical University of Graz, Department of Pathology, A-8036 Graz, Austria.
EM sebastian.mannweiler@uni-graz.at
CR Aoki T, Sasano M, Ikeuchi D, et al: Coexistence of primary colonic malignant lymphoma and rectal adenocarcinoma. Jpn J Gastroenterol Surg 34: 54-58, 2001.
Beham-Schmid C, Beham A, Jakse R, et al: Extranodal follicular dendritic cell tumour of the nasopharynx. Virchows Arch 432: 293-298, 1998.
Camunas Mohinelo F, Requena P M, Zaragoza J M, et al: A. Tumor de colision gastrico con metaplasia osea. Rev Esp Enf Digest 89: 317-319, 1997.
Carr N, Remotti H, Sobin L: Dual carcinoid/epithelial neoplasia of the appendix. Histopathology 27: 557-562, 1995.
Chazouilleres O, Andreani T, Boucher J, et al: Adenocarcinome rectal associe a un lymphome, “collision tumor”). Gastroenterol Clin Biol 14: 185-186, 1990.
Corsi A, Bosman C: Adenocarcinoma and atypical carcinoid: morphologic study of a gastric collision-type tumor in the carcinoma- carcinoid spectrum. Ital J Gastroenterol 27: 303-308, 1995.
Frierson H, Bellafiore F, Gaffey M, et al: Cytokeratin in anaplastic large cell lymphoma. Mod Pathol 7: 317-321, 1994.
Furuya M, Saito Y, Funakosi K, et al: A caseof lymphomatous polyposis of the gastrointestinal tract. Endosc Forum Dig Dis 13: 200-204, 1997.
Ghose A, Dasgupta J, Konar A, et al: Collision tumor of gastrointestinal tract. Indian J Gastroenterol 13: 29-30, 1994.
Goteri G, Ranaldi R, Rezai B, et al: Synchronous mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the stomach. Am J Surg Pathol 21: 505-509, 1997.
Lasota J, Hyjek E, Koo C, et al: Cytokeratin-positive large-cell lymphomas of B-cell lineage. A study of five phenotypically unusual cases verified by polymerase chain reaction. Am J Surg Pathol 20: 346-354, 1996.
Mir-Madjlessi S, Vafai M, Khademi J, et al: Coexisting primary malignant lymphoma and adenocarcinoma of the large intestine in an IgA-deficient boy. Dis Colon Rectum 27: 822-824, 1984.
Morishita Y, Tanaka T, Kato K, et al: Gastric collision tumor, carcinoid and adenocarcinoma, with gastritis cystica profunda. Arch Pathol Lab Med 115: 1006-1010, 1991.
Nakamura S, Aoyagi K, Iwanaga S, et al: Synchronous and metachronous primary gastric lymphoma and adenocarcinoma: A clinicopathologic study of 12 patients. Cancer 79: 1077- 1085, 1997.
Nishino N, Konno H, Baba S, et al: Synchronous lymphoma and adenocarcinoma occuring as a collision tumor in the stomach: Report of a case. Surg Today 26: 508-512, 1996.
Popper H, Winter E, Hofler G: DNA of mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissue in tuberculosis and sarcoidosis detected by polymerase chain reaction. Am J Clin Pathol 101: 738- 741, 1994.
Schmid C, Sargent C, Isaacson PL: H cells of nodular lymphocyte predominant Hodgkin´s disease show immunoglobulin light-chain restriction. Am J Pathol 139: 1281-1289, 1991.
Wagle S, Mohandas K, Vazifdar K, et al: Synchronous adenocarcinoma and lymphoma of the colon. Indian J Gastroenterol 16: 28-29, 1997.
Williams I, Williams N, Stock D, et al: Collision tumour of the ampulla of Vater: Carcinoid and adenocarcinoma. HPB Surg 10: 241-244, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 188
EP 192
PG 5
ER
PT J
AU Vargas-Gonzalez, R
Sotelo-Avila, C
Coria, SA
AF Vargas-Gonzalez, Roberto
Sotelo-Avila, Cirilo
Coria, Solis Araceli
TI Renal Medullary Carcinoma in a Six-Year-Old Boy with Sickle Cell Trait
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE sickle cell disease; renal medullary carcinoma; collecting duct carcinoma
ID sickle cell disease; renal medullary carcinoma; collecting duct carcinoma
AB Renal medullary carcinoma (RMC), an aggressive malignant epithelial neoplasm, first emerged as a distinct clinicopathologic entity in 1995. It affects individuals 40 years of age or younger and is strongly associated with sickle cell disease or trait. The majority of patients with RMC have widely disseminated disease at the time of diagnosis and most fail to respond to both chemotherapy and radiotherapy. Mortality approaches 100%, and death usually occurs within a few months to a year of diagnosis. We report a 6-year-old African-American boy with a history of gross hematuria who died four weeks after diagnosis of disseminated metastatic disease. Autopsy showed a 4.4-cm renal mass with metastases to the contra lateral kidney, liver, lungs and multiregional lymph nodes. RMC should be included in the differential diagnosis of any patient 40 years old or younger with a history of hemoglobinopathy and gross hematuria and/or abdominal or flank pain. A brief discussion of the differential diagnosis, histogenesis and treatment is presented in this study.
C1 [Vargas-Gonzalez, Roberto] Hospital Para el Nino Poblano, Department of PathologyPuebla, Mexico.
[Sotelo-Avila, Cirilo] Cardinal Glennon Children’s Medical Center, Department of Pathology, 63104-1095 St. Louis, Missouri, USA.
[Coria, Solis Araceli] Hospital Infantil de Mexico Federico Gomez, Department of PediatricsMexico City, Mexico.
RP Sotelo-Avila, C (reprint author), Cardinal Glennon Children’s Medical Center, Department of Pathology, 63104-1095 St. Louis, USA.
EM Cirilo_Sotelo_MD@ssmhc.com
CR Berman LB: Sickle cell nephropathy. JAMA 228:1279, 1974.
Davis CJJ, Mostofi FK, Sesterhenn IA: Renal medullary carcinoma: the seventh sickle cell nephropathy. Am J Surg Pathol 19: 1-11, 1995.
Avery RA, Harris JE, Davis CJJ, et al: Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor. Cancer 78: 128-132, 1996.
Dimashkieh H, Choe J, Mutema G: Renal medullary carcinoma a report of two cases and review of the literature. Arch Pathol Lab Med 127:e 135-138, 2003.
Swartz MA, Karth J, Schneider DT et al.Renal medullary carcinoma: Clinical, pathologic, immunohistochemical and genetic analysis with pathogenic implications. Urology 60: 1083-89, 2002.
Davidson AJ, Choyke PL, Hartman DS, Davis CJ Jr. Renal medullary carcinoma associated with sickle cell trait: radiologic findings. Radiology 195: 83-85, 1995.
Srigley JR, Eble JN: Collecting duct carcinoma of kidney. Semin Diagn Pathol 15: 54-67, 1998.
Mostofi FK, Vorder Bruegge CF, Diggs LW: Lesions in kidneys removed for unilateral hematuria in sickle cell disease. Arch Pathol 63: 336-51, 1957.
Pham PT, Pham PC, Wilkinson AH, et al: Renal abnormalities in patients in sickle cell disease. Kidney Int 57: 1-8, 2000.
Ataga KI, Orringer EP: Renal abnormalities in sickle cell disease. Am J Hematol 63: 205-211, 2000.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 193
EP 195
PG 3
ER
PT J
AU Bal, N
Erdogan, A
Kayaselcuk, F
Tarim, E
Tuncer, I
AF Bal, Nebil
Erdogan, Aslan
Kayaselcuk, Fazilet
Tarim, Ebru
Tuncer, Ilhan
TI Vulvar Syringoma Aggravated by Pregnancy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE pregnancy; syringoma; vulva
ID pregnancy; syringoma; vulva
AB Syringoma is a benign tumors of eccrine sweat gland. They appear as multiple, tiny, firm, skin-colored papules. Vulvar involvement of syringoma is rare. Only 24 cases with vulvar syringoma have been previously reported in the literature. The majority of patients with vulvar syringomas are asymptomatic. A case of syringoma of the vulva exacerbated during pregnancy is presented. The case appears remarkable for the experienced aggravated pruritic symptoms of the patient during her pregnancy.
C1 [Bal, Nebil] Baskent University, Department of Pathology, Adana Hastanesi, Yuredir, 01250 Adana, Turkey.
[Erdogan, Aslan] Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Department of Gynecology and ObstetricAdana, Turkey.
[Kayaselcuk, Fazilet] Baskent University, Department of Pathology, Adana Hastanesi, Yuredir, 01250 Adana, Turkey.
[Tarim, Ebru] Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Department of Gynecology and ObstetricAdana, Turkey.
[Tuncer, Ilhan] Baskent University, Department of Pathology, Adana Hastanesi, Yuredir, 01250 Adana, Turkey.
RP Bal, N (reprint author), Baskent University, Department of Pathology, 01250 Adana, Turkey.
EM nebilbal@yahoo.com
CR Gerdsen R, Wenzel J, Uerlich M et al. Periodic genital pruritus caused by syringoma of the vulva. Acta Obstet Gynecol Scand 81:369-370, 2002
Tay YK, Tham SN, Teo R. Localized vulvar syringoma – an unusual cause of pruritus vulvae. Dermatology 192:62-63, 1996
Turan C, Ugur M, Kutluay L et al. Vulvar syringoma exacerbated during pregnancy. Eur J Obstet Gynecol Reprod Biol 64:141- 142, 1996
Belardi MG, Maglione MA, Vighi S, et al. Syringoma of the vulva. A case report. J Reprod Med 39:957-959, 1994
Nogita T, Kawashima M. Subclinical syringoma coexisting with nevocellular nevus on the vulva. J Dermatol 20:188-189, 1993
Trager JD, Silvers J, Reed J et al. Neck and vulvar papules in an 8-year-old girl. Arch Dermatol 135:203-206, 1999
Kurman RJ. Blaustein’s Pathology of the Female Genital Tract, Fifth ed. New York: Springer-Verlag Press, 2002.
Elder D. Lever’s Histopathology of the Skin, Eight ed. Philadelphia: Lippincott-Raven Publishers, 1997.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 196
EP 197
PG 2
ER
PT J
AU Megyesi, M
Berta, M
Khoor, A
AF Megyesi, Maria
Berta, Maria
Khoor, Andras
TI Endobronchial Large Cell Neuroendocrine Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE neuroendocrine carcinoma; lung
ID neuroendocrine carcinoma; lung
AB Lung tumors with neuroendocrine morphology include typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The World Health Organization emphasizes the importance of mitotic count in differentiating these tumors. We studied the case of a 58-year-old male nonsmoker with recurrent pneumonia and an endobronchial mass, which was removed by right middle lobectomy. The patient was alive with no recurrent disease at 36-month follow-up. Histologically, the tumor showed welldeveloped neuroendocrine morphology but contained up to 20 mitoses per 10 high-power fields and was therefore diagnosed as a large cell neuroendocrine carcinoma. However, several features, including the carcinoid-like morphology and endobronchial location of the tumor, absence of smoking history, and promising clinical course, were more characteristic of an atypical carcinoid than of a large cell neuroendocrine carcinoma. It may be necessary to redefine histologic criteria to allow a higher mitotic rate for classification as an atypical carcinoid.
C1 [Megyesi, Maria] Central Railway Hospital and Polyclinic, Department of PathologyBudapest, Hungary.
[Berta, Maria] Central Railway Hospital and Polyclinic, Department of PathologyBudapest, Hungary.
[Khoor, Andras] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Road, 32224 Jacksonville, Florida, USA.
CR Travis WD, Sobin LH: Histological Typing of Lung and Pleural Tumours. 3rd ed. Berlin, Germany: Springer-Verlag; 1999
Colby TV, Koss MN, Travis WD: Tumors of the Lower Respiratory Tract. Washington, DC: Armed Forces Institute of Pathology; 1995
Travis WD, Linnoila RI, Tsokos MG, et al: Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma: an ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 15:529- 553, 1991
Jung KJ, Lee KS, Han J, et al: Large cell neuroendocrine carcinoma of the lung: clinical, CT, and pathologic findings in 11 patients. J Thorac Imaging 16:156-162, 2001
Travis WD, Rush W, Flieder DB, et al: Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22:934-944, 1998
Dresler CM, Ritter JH, Patterson GA, Ross E, Bailey MS, Wick MR: Clincal-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 63:180- 185, 1997
Mazieres J, Daste G, Molinier L, et al. Large cell neuroendocrine carcinoma of the lung: pathological study and clinical outcome of 18 resected cases. Lung Cancer 37:287-292, 2002
Takei H, Asamura H, Maeshima A, et al. Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eightyseven cases. J Thorac Cardiovasc Surg 124:285-292, 2002
Arrigoni MG, Woolner LB, Bernatz PE. Atypical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 64:413-421, 1972
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 198
EP 200
PG 3
ER
PT J
AU Bilgic, B
Ates, EL
Demiryont, M
Ozger, H
Dizdar, Y
AF Bilgic, Bilge
Ates, Esberk Lora
Demiryont, Misten
Ozger, Harzem
Dizdar, Yavuz
TI Malignant Peripheral Nerve Sheath Tumors Associated With Neurofibromatosis Type 1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Neurofibromatosis; malignant peripheral nerve sheath tumours; sarcoma; nonossifying fibroma
ID Neurofibromatosis; malignant peripheral nerve sheath tumours; sarcoma; nonossifying fibroma
AB We report 4 cases of malignant peripheral nerve sheath tumors (MPNST) with neurofibromatosis type 1 (NF1). Mean age was 29.5. Two of them had a family history. Three of them were male. All of them had enlarging mass and pain in the background of neurofibromas. Locations were popliteal, thigh and forearm. The masses were greater than 5 cm in diameter in each case. In two cases the mass was showing continuity with a nerve. One patient had a nonossifying fibroma as well as a MPNST. Wide excision and radiotherapy were applied to three of the patients. One of them did not take any therapy after surgical resection. Two of the patients died of lung metastases after a mean period of 12.5 months. In a majority of NF1 patients MPNST emerges from a preexisting neurofibroma. The patients with NF1 are at greatest risk for developing sarcomas, so they should be followed closely.
C1 [Bilgic, Bilge] Istanbul Medical Faculty, Department of Pathology, Capa, 34390 Istanbul, Turkey.
[Ates, Esberk Lora] Istanbul Medical Faculty, Department of Pathology, Capa, 34390 Istanbul, Turkey.
[Demiryont, Misten] Istanbul Medical Faculty, Department of Pathology, Capa, 34390 Istanbul, Turkey.
[Ozger, Harzem] Istanbul University, Istanbul Medicine Faculty, Department of Orthopaedic SurgeryIstanbul, Turkey.
[Dizdar, Yavuz] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
RP Ates, EL (reprint author), Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
EM loraates@hotmail.com
CR Blatt J, Jaffe R, Deutsch M, et al: Neurofibromatosis and childhood tumors. Cancer 57: 1225–1229, 1986
D’Agostina AN, Soule EH, Miller RH: Sarcomas of the peripheral nerves and soft tissues associated with multiple neurofibromatosis, Von Recklinghausen’s Disease). Cancer 16: 1015–1027, 1963
Ducatman BS, Scheithauer BW: Malignant peripheral nerve sheath tumors with divergent differentiation. Cancer 54: 1049–1057, 1984
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Ferner RE, Lucas JD, O’Doherty MJ, et al: Evaluation of 18 Fluorodeoxyglucose positron emission tomography, 18 FDG PET, in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1. J Neurol Neurosurg Psychiatry 68: 353-357, 2000
Halliday AL, Sobel RA, Martuza RL: Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. J Neurosurg 74: 248–253, 1991
Hajdu SI: Peripheral nerve sheath tumors, histogenesis, classification and prognosis. Cancer 72: 3549–3552, 1993
Hruban RH, Shiu MH, Senie RT, et al: Malignant peripheral nerve sheath tumors of the buttock and lower extremity, A study of 43 Cases. Cancer 66: 1253–1265, 1990
King AA, DeBaun MR, Riccardi VM, et al: Malignant peripheral nerve sheath tumors in neurofibromatosis 1. Am J Med Genet 93: 388-392, 2000
Nussbaum RL, McInnes RR, Willard HF: Genetics In Medicine. Genetics and Cancer, W. B. Saunders Company: Philadelphia, 2001.
Rasmussen SA, Overman J, Thomson SAM, et al: Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1. Genes, Chromosomes, Cancer 28: 425–431, 2000
Schmidt H, Wurl P, Taubert H, et al: Genomic imbalances of 7p and 17q in malignant peripheral nerve sheath tumors are clinically relevant. Genes, Chromosomes, Cancer 25: 205–211, 1999
Topsakal CD, Akdemir I, Tiftikci M, et al: Malignant schwannoma of the sciatic nerve originating in a spinal plexiform neurofibroma associated with neurofibromatosis type 1. Neurol Med Chir, Tokyo, 41: 551–555, 2001
Wanebo JE, Malik JM, VandenBerg SR, et al: Malignant peripheral nerve sheath tumors, A clinicopathologic study of 28 cases. Cancer 71: 1247–1253, 1993
Weiss SW, Goldblum JR: Benign tumors of the peripheral nerves. Malignant tumors of the peripheral nerves. Enzinger and Weiss’s Soft Tissue Tumors. Mosby, St Louis, 2001.
Wick MR, Swanson PE, Scheithauer BW, et al: Malignant peripheral nerve sheath tumor. An immunohistochemical study of 62 cases. Am J Clin Pathol 87: 425–433, 1987
Woodruff JM, Christensen WN: Glandular peripheral nerve sheath tumors. Cancer 72: 3618–3628, 1993
Woodruff JM: Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet, Semin Med Genet, 89: 23–30, 1999
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2003
VL 9
IS 3
BP 201
EP 205
PG 5
ER
PT J
AU Szabo, E
Lotz, G
Paska, Cs
Kiss, A
Schaff, Zs
AF Szabo, Erzsebet
Lotz, Gabor
Paska, Csilla
Kiss, Andras
Schaff, Zsuzsa
TI Viral Hepatitis: New Data on Hepatitis C Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE viral hepatitis; hepatitis C; chronic hepatitis
ID viral hepatitis; hepatitis C; chronic hepatitis
AB Viral hepatitis (VH) is almost as old as human beings, at least as old as known human history. However, the natural history and the epidemiology of the disease has undergone changes during the centuries and even recently we have been facing several new aspects. The estimated global prevalence is around 3-5%, which means that approximately 400 million patients are infected with hepatitis B virus and that there are 170 million infections with hepatitis C virus. The mortality figures are projected to show a 2- to 3-fold increase over the next two decades as hepatitis C virus-infected patients develop cirrhosis, which makes this the leading indication for liver transplantation. These data point to the importance of VH being a significant public health problem worldwide. The list of hepatotropic viruses is well known, including hepatitis A (HAV), B (HBV), C (HCV), D (HDV), E (HEV), G (HGV) and F (HFV). HGV and HFV are excluded from the present review, mainly because they are questionable in relation to the causation of liver disease. Our knowledge of HAV, HBV, HDV and HEV has accumulated over the last decade, so the present discussion is focused on HCV, which is currently generating considerable concern and controversy, and is the leading cause of chronic liver disease worldwide. The main questions to be discussed, are: the characterization of the agents’ viral genotypes/subtypes, the viral-cell interaction, the pathogenesis of VH, the extrahepatic manifestations of viral infection and hepatocarcinogenesis.
C1 [Szabo, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Paska, Csilla] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Agnello V, Abel G, Elfahal M, et al: Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 96: 12766-12771, 1999
Adinolfi LE, Utili R, Andreana A, et al: Relationship between genotypes of hepatitis C virus and histopathological manifestations in chronic hepatitis C patients. Eur J Gastroenterol Hepatol 12: 299-304, 2000
Alison MR, Poulsom R, Jeffery R, et al: Hepatocytes from nonhepatic adult stem cells. Nature 406: 257, 2000
Alter MJ, Kruszon-Moran D, Nainon OV, et al: The prevalence of hepatitis C virus infection in United States, 1988 through 1994. N Engl J Med 321: 556-562, 1999
Ander RA, Yerian LM, Tretiakova M, et al: cDNA microarray analysis of macroregenerative and dysplastic nodules in endstage hepatitis C virus-induced cirrhosis. Am J Pathol 162: 991-1000, 2003
Armstrong GL, Alter MJ, McQuillan GM, et al: The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 31: 777-782, 2000
Barba G, Harper F, Harada T, et al: Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci USA 94:1200-1205, 1997
Bartenschlager R, Lohmann V: Replication of hepatitis C virus. J Gen Virol 81: 1631-1648, 2000
Bedossa P, Poynard T: The METAVIR cooperative study group. An algorithm for the grading of activity in chronic hepatitis C. Hepatology 24: 289-293, 1996
Bisgaard HC, Holmskov U, Santoni-Rugiu E, et al: Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1. Am J Pathol 161: 1187-1198, 2002
Buendia MA: Genetics of hepatocellular carcinoma. Semin Cancer Biol 10: 185-200, 2000
Chang M, Williams O, Mittler J, Qiuntanilla A, Carithers RL, Perkins J, Corey L, Gretch DR: Dynamics of hepatitis C virus replication in human liver. Am J Pathol 163: 433-444, 2003
Choi J, Xu Z, Ou J-H: Triple decoding of hepatitis C virus RNA by programmed translational frameshifting. Mol Cell Biol 23: 1489-1497, 2003
Crowson AN, Nuovo G, Ferri C, et al: The dermatopathologic manifestations of hepatitis C infection: A clinical, histological, and molecular assessment of 35 cases. Hum Pathol 34: 573- 579, 2003
De Martino L, Sampaolo S, Tucci C, et al: Viral RNA in nerve tissues of patients with hepatitis C infection and peripheral neuropathy. Muscle and Nerve 27: 102-104, 2003
De Vos R, Verslype C, Depla E, et al: Ultrastructural visualization of hepatitis C virus components in human and primate liver biopsies. J Hepatol 37: 370-379, 2002
Di Bisceglie AM: Hepatitis C – Virology and future antiviral targets. Am J Med 107: 45S-48S, 1999
Dudas J, Kovalszky I, Gallai M, et al: Expression of decorin, transforming growth factor beta 1, tissue inhibitor metalloproteinase 1, 2 and type IV collagenases in chronic hepatitis. Am J Clin Path 115: 725-735, 2001
Edamoto Y, Hara A, Biernat W, et al: Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Int J Cancer 106: 334-341, 2003
Forbes S, Vig P, Poulsom R, et al: Hepatic stem cells. J Pathol 197: 510-518, 2002
Gao G, Buskel Z, Seef L et al: Drift in the hypervariable region of the hepatitis C virus during 27 years in two patients. J Med Virol 68: 60-67, 2002
Gardner JP, Durso RJ, Arrigale RR, et al: L-sign, CD 209L, is a liver-specific capture receptor for hepatitis C virus. Proc Natl Acad Sci USA 100: 4498-4503, 2003
Gasztonyi B, Par A, Kiss K, et al: Activation of the nuclear factor kappa B – key role in oncogenesis? Chronic hepatitis C virus infection and lymphomagenesis. Orv Hetil 144: 863-868, 2003
Gervain J, Simon G, Papp I, et al: Analysing the type and subtype of hepatitis virus C of chronic viral hepatitis patients in Hungary. Orv Hetil 142: 1315-1319, 2001
Gervain J, Czibula A, Simon J, et al: Structure analysis of the PKR-binding region of HCV 1b samples from patients with chronic hepatitis C and the correlation with IFN-sensitivity. Orv Hetil 144: 1179-1184, 2003
He Y, Katze MG: To inferfere and to anti-interfere: The interplay between hepatitis C virus and interferon. Viral Immunol 15: 95-119, 2002
Houghton M: Hepatitis C viruses. In: Fields Virology, ed 3., Eds: Fields BN, Knipe DM, Howley PM), Lippincott-Raven, Philadelphia, 1996, pp. 1035-1068
International Hepatology Informatics Group: Diseases of the Liver and Biliary Tract. Standardization of Nomenclature, Diagnostic Criteria, and Prognosis. Raven Press, New York, 1994.
Ishak K, Baptista A, Bianchi L, et al: Histological grading and staging of chronic hepatitis. J Hepatol 22: 696-699, 1995
Iwarson S, Schaff Zs, Seto BJ, et al: Retrovirus-like particles in hepatocytes of patients with transfusion-aquired non-A, non-B hepatitis. J Med Virol 16: 37-45, 1985
Jarmay K, Gallai M, Karacsony G, et al: Decorin and actin expression and distribution in chronic hepatitis C following interferon-alfa-2b treatment. J Hepatol 32: 993-1002, 2000
Kapadia SB, Brideau-Andersen A, Chisari FV: Interference of heptitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci USA 100: 2014-2018, 2003
Knodell RG, Ishak KG, Black WC, et al: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1: 431-435, 1981
Korbling M, Katz RL, Khanna A, et al:Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 346: 738-746, 2002
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Lotz G, Simon Zs, Szalay F, et al: Localization of hepatitis C virus RNA on human red blood cells by RT-in situ PCR technique. Scand J Gastroenterol 37: 578-584, 2002
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Mihm S, Fayyazi A, Hartmann H, et al: Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. Hepatology 25: 735-739, 1997.
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Par A, Telegdy L, Dalmi L, et al: Therapy for chronic hepatitis C. J Physiol 95: 399-405, 2001
Pileri P, Uematsu Y, Campagnoli S, et al: Binding of hepatitis C virus to CD81. Science 282: 938-941, 1998
Pina Dore M, Realdi G, Mura D, et al: Genomic instability in chronic viral hepatitis and hepatocellular carcinoma. Hum Pathol 32: 698-703, 2001
Podanyi B: Extrahepatic manifestations and skin diseases associated with hepatitis C virus infection. Orvoskepzes 1: 1-48, 2003
Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 349: 825-832, 1997
Ramalho F, Costa A, Pires A, et al: Correlation of genotypes and route of transmission with histologic activity and disease stage in chronic hepatitis C. Digest Dis Sci 45: 182-187, 2000
Rozario R, Ramakrishna B: Histopathological study of chronic hepatitis B and C: a comparison of two scoring systems. J Hepatol 38: 223-229, 2003
Rubbia-Brandt L, Leandro G, Spahr L, et al: Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3. Histopathology 39: 119-124, 2001
Scarselli E, Ansuini H, Cerino R, et al: The human scavenger receptor class B type I is a novel candidate receptor for the hepatitits C virus. EMBO J 21: 5017-5025, 2002
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Schaff Zs, Lotz G, Eder G, et al: Pathomorphology and apoptosis in viral hepatitis. In: Therapies for Viral Hepatitis., Eds: Schinazi RF, Sommadossi JP, Thomas H), Int. Med. Press Ltd, London, 1998, pp. 77-86
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Scheuer PJ: Assessment of liver biopsies in chronic hepatitis: how is it best done? J Hepatol 38: 240-242, 2003
Scheuer PJ, Davies SE, Dhillon AP: Histopathological aspects of viral hepatitis. J Viral Hep 3: 277-283, 1996
Serfaty L, Andreani T, Giral P, et al: Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 34: 428-434, 2001
Shimotohno K: Hepatitis C virus and its pathogenesis. Semin Cancer Biol 10: 233-240, 2000
Smith MW, Yue ZN, Geiss GK, et al: Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma. Cancer Res 63: 859-864, 2003
Tabor E: Hepatocellular carcinoma: global epidemiology. Digest Liver Dis 33: 115-117, 2001
Wanless IR, Nakashima E, Sherman M: Regression of human cirrhosis. Arch Pathol Lab Med 124: 1599-1607, 2000
Wasley A, Alter MJ: Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 20: 1-16, 2000
WHO Global surveillance and control of hepatitis C. Report of a WHO consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepatol 6: 35-47, 1999
Wilson JA, Jayasena S, Khvorova A et al: RNA inferference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells. Proc Natl Acad Sci 100: 2783-2788, 2003
Yen T, Keeffe E, Ahmed A: The epidemiology of hepatitis C virus infection. J Clin Gastroenterol 36: 47-53, 2003.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 215
EP 221
PG 7
ER
PT J
AU Keresztes, K
Takacs, M
Horanyi, M
Miltenyi, Zs
Illes,
AF Keresztes, Katalin
Takacs, Maria
Horanyi, Margit
Miltenyi, Zsofia
Illes, Arpad
TI HCV and HGV Infection in Hodgkin's Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hodgkin’s disease; hepatitis C virus; hepatitis G virus
ID Hodgkin’s disease; hepatitis C virus; hepatitis G virus
AB Numerous observations imply that the pathogenesis of malignant lymphomas is multifactorial and that viruses probably play an important etiologic role. Besides Epstein-Barr virus, there might be other viruses among the causes of Hodgkin's disease. A total of 111 randomly selected patients with Hodgkin's disease were included in this study, and hepatitis C and G viruses were tested with polymerase chain reaction. The results were compared to hepatitis C and G virus infection ratios assessed by polymerase chain reaction in the Hungarian blood bank. Hepatitis C virus was diagnosed in 10 (9%) patients, and hepatitis G virus in 9 (8,1%), which is a 12-fold and a 1,5-fold infection rate as compared to that of the Hungarian blood bank, respectively. There was no significant difference between hepatitis positive and negative patients concerning mean age at the time of diagnosis, sex, disease stage, histology type, treatment applied, risk factors in the history of the infection and liver enzymes. Hepatitis C virus positivity in patients with Hodgkin's disease differs significantly from that in blood donors. Based on these results and data in the literature, no definite statement can be made on the etiological role of viruses, but further studies are needed.
C1 [Keresztes, Katalin] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22., H-4004 Debrecen, Hungary.
[Takacs, Maria] Bela Johan National Institute of Hygiene, Department of VirologyBudapest, Hungary.
[Horanyi, Margit] OGYK, Virus Nucleic Acid LaboratoryBudapest, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22., H-4004 Debrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22., H-4004 Debrecen, Hungary.
RP Keresztes, K (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, H-4004 Debrecen, Hungary.
EM katalin@iiibel.dote.hu
CR Barna TK, Ozsvar Z, Szendrenyi V, et al: Hepatitis C virus antibody in the serum of blood donors. Orv Hetil 10: 507-511, 1996
Cividini A, Rebucci C, Silini E, et al: Is the natural history of hepatitis C virus carriers with normal aminotransferase really benign? Gastroenterology 121: 1526-1527, 2001
Fuchs K, Motz M, Schreier E, et al: Characterization of nucleotide sequences from European hepatitis C virus isolates. Gene 103: 163-169, 1991
Gasztonyi B, Par A, Szomor A, et al: Hepatitis C virus infection associated with B-cell non-Hodgkin’s lymphoma in Hungarian patients. Br J Haemat 110: 498-499, 2000
Halasz R, Weiland O, and Sallberg M: GB virus C/hepatitis G virus. Scand J Infect Dis 33: 572-580, 2001
Jarrett RF, and MacKenzie J: Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin’s disease. Sem Haematol 36: 26-29, 1999
Keenan RD, Harrison P, Joffre L, et al: Hepatitis G virus, HGV, and lymphoproliferative disorders. Br J Haematol 99: 710, 1997
Khudyakov YE, Cong ME, Bonafonte MT, et al: Sequence variation within a nonstructural region of the hepatitis G virus genome. J of Virology 71: 6875-6880, 1997
Markovic S, Drozina G, Vovk M, et al: Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 46: 2925-2930, 1999
Par A, Telegdy L, Gogl A, et al: Interferon therapy of chronic viral hepatitis in Hungary: 5-year experience. A multicenter study. Orv Hetil 140: 1227-1233, 1999
Persico M, De Renzo A, Persico E, et al: Hepatitis G virus in patients with Hodgkin’s lymphoma. Br J Haematol 103: 1206, 1998
Pozzato G, Mazzaro C, Santini G, et al: Hepatitis C virus and non-Hodgkin’s lymphomas. Leuk Lymph 22: 53-60, 1996
Szabo A, Heemann U, Muller V, et al: Hepatitis G virus infection in adults and children after kidney transplantation. Orv Hetil 140: 1619-1623, 1999
Zuckerman E, Zuckerman T, Douer D, et al: Liver dysfunction in patients with hepatitis C virus undergoing chemotherapy for hematologic malignancies. Cancer 83: 1224-1230, 1998
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 222
EP 225
PG 4
ER
PT J
AU Al-Moundhri, M
Nirmala, V
Al-Mawaly, K
Ganguly, Sh
Burney, I
Rizvi, A
Grant, Ch
AF Al-Moundhri, Mansour
Nirmala, Vadakkepat
Al-Mawaly, K
Ganguly, Shyam
Burney, A. Ikram
Rizvi, J. Azhar
Grant, Christopher
TI Significance of p53, Bcl-2, and HER-2/neu Protein Expression in Omani Arab Females with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; p53; bcl-2; HER-2; arab-females
ID breast cancer; p53; bcl-2; HER-2; arab-females
AB Racial disparity in the presentation of breast cancer and the outcome of its treatment is well established. However, the causes remain unexplained. The scarcity of reports about the prognostic significance of p53, bcl-2, and HER-2/neu in Arab females with breast cancer has been the impetus to this study. We evaluated the prognostic significance of altered expression of p53, bcl-2, HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. We have retrospectively analyzed the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002. The expression of the above proteins was correlated with other prognostic factors and univariate and multivariate analysis was carried out for all prognostic factors. Overexpression of p53 significantly correlated with younger age (<40), pre-menopausal status, poor differentiation with inverse correlation with bcl-2 expression. Expression of bcl-2 immunopostivity significantly correlated to low histological grade and positive estrogen and progesterone receptor status. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but not Her-2/neu overexpression. Expression patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab population which may help to stratify these patients into different risk groups.
C1 [Al-Moundhri, Mansour] Sultan Qaboos University, Department of Medicine, Medical Oncology Unit, 123 Al-Khod, Oman.
[Nirmala, Vadakkepat] Sultan Qaboos University, Department of PathologyMuscat, Oman.
[Al-Mawaly, K] Sultan Qaboos University, Department of PathologyMuscat, Oman.
[Ganguly, Shyam] Sultan Qaboos University, Department of Epidemiology and Medical StatisticsMuscat, Oman.
[Burney, A. Ikram] Sultan Qaboos University, Department of Medicine, Medical Oncology Unit, 123 Al-Khod, Oman.
[Rizvi, J. Azhar] Sultan Qaboos University, Department of Medicine, Medical Oncology Unit, 123 Al-Khod, Oman.
[Grant, Christopher] Sultan Qaboos University, Department of Surgery College of MedicineMuscat, Oman.
RP Al-Moundhri, M (reprint author), Sultan Qaboos University, Department of Medicine, Medical Oncology Unit, 123 Al-Khod, Oman.
CR Rose DP, Royak-Schaler R: Tumor biology and prognosis in black breast cancer patients: a review. Cancer Detect Prev 25:16- 31, 2001
Ikpatt OF, Kuopio T, Collan Y: Proliferation in African breast cancer: biology and prognostication in Nigerian breast cancer material. Mod Pathol 15:78, 2002
Simon MS SR: Racial differences in breast cancer survival: the interaction of socio-economic status and tumor biology. Am J Obstet Gynecol 176:233-236, 1997
Cheng SH, Tsou MH, Liu MC, et al: Unique features of breast cancer in Taiwan. Breast Cancer Res Treat 63:213-23, 2000
Chow LW TA, Cheung KL, Au GK, et al: Current status of breast cancer in Hong Kong. Chin Med J, Engl, 110:474-8, 1997
Ezzat A RM, Zwaan F, Brigden M, et al: The lack of age as a significant prognostic factor in non-metastatic breast cancer. Eur J Surg Oncol 24:23-7, 1998
Fakhro AE FB, Al-Asheeri N, Al-Ekri SA: Breast cancer: patient characteristics and survival analysis at Salmaniya Medical Complex, Bahrain. Eastern Mediterranean Health Journal 5:430-439, 1999
Maalej M FH, Ben Salem S, Daoud J, et al: Breast cancer in Tunisia: clinical and epidemiological study. Bull Cancer 86:302- 6., 1999
Malik IA: Clinico-pathological features of breast cancer in Pakistan. J Pak Med Assoc 52:100-4, 2002
Slamon DJ, deKernion JB, Verma IM, et al: Expression of cellular oncogenes in human malignancies. Science 224:256-62, 1984
Bankfalvi A, Tory K, Kemper M, et al: Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma. Pathol Res Pract 196:489-501, 2000
Barbareschi M, Caffo O, Veronese S, et al: Bcl-2 and p53 expression in node-negative breast carcinoma: a study with long-term follow-up. Hum Pathol 27:1149-55, 1996
Ferrero-Pous M, Hacene K, Bouchet C, et al: Relationship between c-erbB-2 and other tumor characteristics in breast cancer prognosis. Clin Cancer Res 6:4745-54, 2000
Jansen RL, Joosten-Achjanie SR, Volovics A, et al: Relevance of the expression of bcl-2 in combination with p53 as a prognostic factor in breast cancer. Anticancer Res 18:4455-62, 1998
Le MG, Mathieu MC, Douc-Rasy S, et al: c-myc, p53 and bcl-2, apoptosis-related genes in infiltrating breast carcinomas: evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients. Int J Cancer 84:562-7, 1999
Nunes RA, Harris LN: The HER2 extracellular domain as a prognostic and predictive factor in breast cancer. Clin Breast Cancer 3:125-35, 2002
Ross JS, Fletcher JA: The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 16:413-28, 1998
Sahin AA: Biologic and clinical significance of HER-2/neu, cerbB-2, in breast cancer. Adv Anat Pathol 7:158-66, 2000
Silvestrini R, Veneroni S, Daidone MG, et al: The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst 86:499- 504, 1994
Sjogren S, Inganas M, Lindgren A, et al: Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol 16:462-9, 1998
Zhang GJ, Tsuda H, Adachi I, et al: Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins. Jpn J Clin Oncol 27:371-7, 1997
el-Ahmady O, el-Salahy E, Mahmoud M, et al: Multivariate analysis of bcl-2, apoptosis, p53 and HER-2/neu in breast cancer: a short-term follow-up. Anticancer Res 22:2493-9, 2002
Temmim L, Baker H, Sinowatz F: Immunohistochemical detection of p53 protein expression in breast cancer in young Kuwaiti women. Anticancer Res 21:743-8, 2001
Doglioni C, Dei Tos AP, Laurino L, et al: The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status. Virchows Arch 424:47-51, 1994
al-Lawati JA, Santhosh-Kumar CR, Mohammed AJ, et al: Cancer incidence in Oman, 1993-1997. East Mediterr Health J 5:1035-41, 1999
Rosanelli GP, Steindorfer P, Wirnsberger GH, et al: Mutant p53 expression and DNA analysis in human breast cancer comparison with conventional clinicopathological parameters. Anticancer Res 15:581-6, 1995
Fresno M, Molina R, Perez del Rio MJ, et al: p53 expression is of independent predictive value in lymph node-negative breast carcinoma. Eur J Cancer 33:1268-74, 1997
Bosari S, Lee AK, Viale G, et al: Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with longterm follow-up. Virchows Arch A Pathol Anat Histopathol 421:291-5, 1992
Quinn CM, Ostrowski JL, Harkins L, et al: Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c-erbB-2 proteins. Histopathology 33:531-6, 1998
Hellemans P, van Dam PA, Weyler J, et al: Prognostic value of bcl-2 expression in invasive breast cancer. Br J Cancer 72:354- 60, 1995
Ioachim EE, Malamou-Mitsi V, Kamina SA, et al: Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. Anticancer Res 20:4221-5, 2000
Haldar S, Negrini M, Monne M, et al: Down-regulation of bcl-2 by p53 in breast cancer cells. Cancer Res 54:2095-7, 1994
Vairo G, Innes KM, Adams JM: Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell survival. Oncogene 13:1511-9, 1996
Miyashita T, Kitada S, Krajewski S, Horne WA, Delia D, Reed JC: Overexpression of the Bcl-2 protein increases the half-life of p21 Bax J Biol Chem 270:26049–26052, 1995
Thor AD, Berry DA, Budman DR, et al: erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst 90:1346-60, 1998
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 226
EP 231
PG 6
ER
PT J
AU Arista-Nasr, J
Martinez-Benitez, B
Valdes, S
Hernandez, M
Bornstein-Quevedo, L
AF Arista-Nasr, Julian
Martinez-Benitez, Braulio
Valdes, Samuel
Hernandez, Mercedes
Bornstein-Quevedo, Leticia
TI Pseudohyperplastic Prostatic Adenocarcinoma in Transurethral Resections of the Prostate
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pseudohyperplastic prostatic adenocarcinoma; diagnosis
ID pseudohyperplastic prostatic adenocarcinoma; diagnosis
AB Pseudohyperplastic prostatic adenocarcinoma is a recently described variety of adenocarcinoma that has been studied in core-needle biopsies and prostatectomy specimens. It is characterized by malignant glands that simulate benign hyperplastic glands with complex, medium to large-sized glands with papillary infoldings, luminal undulations, branching or cystic dilatations, and columnar cells with macronucleoli and nuclear enlargement. Our aim was to define frequency, tumor volume, and histologic features of pseudohyperplastic prostatic adenocarcinoma in transurethral resections of prostate. We studied 250 specimens from transurethral resections; 150 specimens were originally diagnosed as benign glandular hyperplasia, and 100 as conventional prostate adenocarcinomas. Of the 150 biopsies originally diagnosed as benign glandular hyperplasia, two (1.3%) had areas of pseudohyperplastic carcinoma. In both cases the neoplasm was limited to two chips and measured 3 and 4 mm in diameter, respectively. Both patients were asymptomatic 2 and 4 years after diagnosis. Of the 100 biopsies with adenocarcinoma, areas of pseudohyperplastic carcinoma were found in three cases. In the first two these areas were found in two fragments, and in the other case they were found in three chips, and measured 3, 4, and 6 mm, respectively. The clinical course in these cases was unfavorable, and two patients had metastasis. Main histologic findings included crowded glands (5/5), papillary projections (5/5), nuclear enlargement (5/5) macronucleoli (4/5) cystic glandular dilatation (4/5) straight luminal borders (4/5), pink amorphous secretions (4/5) nuclear hyperchromasia (3/5) and transition to small acinar pattern of adenocarcinoma (3/5). In conclusion, pseudohyperplastic prostate carcinoma is rare in transurethral resection specimens and is found in scarce chips. Frequency of false negative results in biopsies originally diagnosed as benign glandular hyperplasia was 1.3%. In biopsies diagnosed as carcinoma, this frequency was 3%. These patients had an adverse clinical course, apparently due to association with areas of conventional adenocarcinoma.
C1 [Arista-Nasr, Julian] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No. 15, 14000 Tlalpan, Mexico.
[Martinez-Benitez, Braulio] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No. 15, 14000 Tlalpan, Mexico.
[Valdes, Samuel] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No. 15, 14000 Tlalpan, Mexico.
[Hernandez, Mercedes] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No. 15, 14000 Tlalpan, Mexico.
[Bornstein-Quevedo, Leticia] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No. 15, 14000 Tlalpan, Mexico.
RP Arista-Nasr, J (reprint author), Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, 14000 Tlalpan, Mexico.
EM pipa5@hotmail.com
CR Muir EG. Carcinoma of the prostate. Lancet 1:667-72,1934
Willis RA. Pathology of tumors. ST. Louis: CV Mosby; 1948, p587.
Ackerman LV.Surgical Pathology. St. Louis: CV Mosby;1964:651.
Humphrey PA, Kaleem Z, Swanson PE, Vollmer RT. Pseudohyperplatic prostatic adenocarcinoma. Am J Surg Pathol 22: 1239-46, 1998
Levi A, Epstein JI. Pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple prostatectomy. Am J Surg Pathol 24:1039-46,2000
Arista-Nasr, Cortes E, Picardo R. Low grade adenocarcinoma simulating benign glandular lesions in needle prostatic biopsy. Rev Invest Clin 49:37-40,1997
Wojno KJ, Epstein JI.The utility of basal cell specific anticytokeratin antibody, 34 beta E12, in the diagnosis of prostate cancer: a review of 228 cases. Am J Surg Pathol 19:251-60,1995
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Bostwick DG Amin MB, Dundore P et al. Architectural patterns of high grade prostatic intraepithelial neoplasia. Hum Pathol 24:298- 310,1993
Bostwick DG, Srigely J, Grignon D et al. Atypical adenomatous hyperplasia of the prostate: morphological criteria for its distinction from well differentiated carcinoma. Hum Pathol 24:819- 32,1993
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 232
EP 235
PG 4
ER
PT J
AU Kamory, E
Kolacsek, O
Otto, Sz
Csuka, O
AF Kamory, Eniko
Kolacsek, Orsolya
Otto, Szabolcs
Csuka, Orsolya
TI hMLH1 and hMSH2 Somatic Inactivation Mechanisms in Sporadic Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sporadic colorectal cancer; mismatch repair; hMLH1; hMSH2; microsatellite instability; allelic imbalance; promoter hypermethylation and inactivation
ID sporadic colorectal cancer; mismatch repair; hMLH1; hMSH2; microsatellite instability; allelic imbalance; promoter hypermethylation and inactivation
AB Much is known about the role of germline inactivation in mismatch repair (MMR) genes in hereditary non-polyposis colorectal cancer (HNPCC), but the impact of somatic MMR gene changes on sporadic colorectal cancer remains to be elucidated. In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms of the two MMR genes hMLH1 and hMSH2 we screened 37 Hungarian sporadic colorectal cancer patients for allelic imbalance (AI), microsatellite instability (MSI), hMLH1 promoter hypermethylation and somatic mutations. Thirteen of the examined tumours (35%) were characterized by low-level MSI and none of the cases belonged to the high MSI group. Nine (24%) and seven (19%) cases had AI at the hMLH1 and hMSH2 genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation of hMLH1, but only two patients had somatic mutations, one for each MMR gene. According to our study on this limited set of cases the most prominent mismatch repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1 promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer.
C1 [Kamory, Eniko] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Kolacsek, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Otto, Szabolcs] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Csuka, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Csuka, O (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, H-1122 Budapest, Hungary.
EM csuka@oncol.hu
CR Konishi M, Kikuchi-Yanoshita R, Tanaka K, et al: Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology 111: 307-317, 1996.
Bevilacqua RAU, Simpson AJG: Methylation of the hMLH1 promoter but no hMLH1 mutations in sporadic gastric carcinomas with high-level microsatellite instability. Int J Cancer 87: 200-203, 2000.
Kastan MB: Genetic Instability and Tumorigenesis. Springer- Verlag Berlin Heidelberg, 1997.
Fishel R, Lescoe MK, Rao MRS, et al: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75: 1027-1038, 1993.
Bronner CE, Baker SM, Morrison PT, et al: Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368: 258-261, 1994.
Hemminki A, Peltomaki P, Mecklin JP, et al: Loss of the wild type MLH1 gene is a feature of hereditary nonpolyposis colorectal cancer. Nat Genet 8: 405-410, 1994.
Kolodner RD, Hall NR, Lipford J, et al: Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations. Cancer Res 55: 242-248, 1995.
Parsons R, Li GM, Longley M, et al: Mismatch repair deficiency in phenotipically normal human cells. Science 268: 738-740, 1995.
Wong IHN: Methylation profiling of human cancers in blood: Molecular monitoring and prognostication. Int J Oncol 19: 1319-1324, 2001.
Kondo E, Furukawa T, Yoshinaga K, et al: Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial cancer but rarely silenced in pancreatic cancer with microsatellite instability. Int J Oncol 17: 535-541, 2000.
Esteller M, Levine R, Baylin SB, et al: hMLH1 promoter hypermethylation is associated with microsatellite instability phenotype in sporadic endometrial carcinoma. Oncogene 16: 2413- 2417, 1998.
Cunningham JM, Christensen ER, Tester DJ, et al: Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58: 3455-3460, 1998.
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Tomlinson IPM, Lambros MBK, Roylance RR: Loss of heterozygosity analysis: practically and conceptually flawed? Genes Chromosomes Cancer 34: 349-353, 2002.
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Kane MF, Loda M, Gaida GM, et al: Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57: 808-811, 1997.
Yanagisawa Y, Akiyama Y, Iida S, et al: Methylation of the hMLH1 promoter in familial gastric cancer with microsatellite instability. Int J Cancer 85: 50-53, 2000.
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Parc YR, Halling KC, Wang L, et al: HMSH6 alterations in patients with microsatellite instability-low colorectal cancer. Cancer Res 60: 2225-2231, 2000.
Kuismanen SA, Holmberg MT, Salovaara R, et al: Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol 56: 1773-1779, 2000.
Furukawa T, Konishi F, Masubuchi S, et al: Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers. Genes Chromosomes Cancer 35: 1-10, 2002.
Porfiri E, Scartozzi M, Piga A, et al: Missense mismatch repair gene alterations, microsatellite instability, and hereditary nonpolyposis colorectal cancer. J Clin Oncol 20: 3178- 3179, 2002.
Brueckl WM, Limmert T, Brabletz T, et al: Mismatch repair deficiency in sporadic synchronous colorectal cancer. Anticancer Res 20: 4727-4732, 2000.
Toyota M, Ohe-Toyota M, Ahuja N, et al: Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. PNAS 97: 710-715, 2000.
Han HJ, Maruyama M, Baba S, et al: Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer, HNPCC). Hum Mol Genet 14: 237-242, 1995.
Maliaka YK, Chudina AP, Belev NF, et al: CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations. Hum Genet 97: 251-255, 1996.
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Liu T, Wahlberg S, Rubio C, et al: DGGE screening of mutations in mismatch repair genes, hMSH2 and hMLH1, in 34 Swedish families with colorectal cancer. Clin Genet 53: 131- 135, 1998.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 236
EP 241
PG 6
ER
PT J
AU Bilgic, B
Mete,
Ozturk, AS
Demiryont, M
Keles, N
Basaran, M
AF Bilgic, Bilge
Mete, Ozgur
Ozturk, A Settar
Demiryont, Misten
Keles, Nesil
Basaran, Mert
TI Synovial Sarcoma: a Rare Tumor of Larynx
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE larynx; synovial sarcoma
ID larynx; synovial sarcoma
AB Synovial sarcoma is a soft tissue sarcoma of unknown histogenesis and occurs predominantly in the lower extremities of young adults. The head and neck is a relative rare location. There are about 10 cases with laryngeal localization in the literature. We present a 24 year-old male with an endolaryngeal mass. Incisional biopsy and the hemilaryngectomy material revealed a biphasic synovial sarcoma. One year later a local recurrence occurred. Tumor excision and neck dissection were performed. Radiotherapy was added. Six months later lung metastases was discovered on thoracic CT. The patient received chemotherapy for 6 courses. The metastases responded well to chemotherapy and the patient is now alive without tumor on radiological and clinical examination after 3.5 years of follow-up.
C1 [Bilgic, Bilge] Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
[Mete, Ozgur] Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
[Ozturk, A Settar] Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
[Demiryont, Misten] Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
[Keles, Nesil] Istanbul Medical Faculty, ENT SurgeryIstanbul, Turkey.
[Basaran, Mert] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
RP Bilgic, B (reprint author), Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
EM eminbilgic@superonline.com
CR Aubert S: Parapharyngeal synovial sarcoma. Ann Pathol 21: 71-75, 2001
Danninger R, Hurner U, Stammberger H: Das Synovialsarkom, ein seltener Tumor des Larynx. Falldarstellung und differentialdiagnostische Uberlegungen. Laryngorhinootologie 73: 442-444, 1994
Dei Tos A, Dal Cin P, Sciot R, et al: Ann Otol Rhinol Laryngol 107: 1080-1085, 1998
Ferlito A, Caruso G: Endolaryngeal synovial sarcoma: An update on diagnosis and treatment. ORL, J Otorhinolaryngol Relat Spec 53: 116-119, 1991
Garenstein A, Neel HB 3rd, Weiland LH, et al: Sarcomas of the larynx. Arch Otolaryngol 106: 8-12, 1980
Gatti WM, Strom CG, Orfei E: Synovial sarcoma of the laryngopharynx. Arch Otolaryngol 101: 633-636, 1975
Geahchan NE, Lambert J, Micheau C, et al: Synovialome malin du larynx. Ann Otolaryngol Chir Cervicofac 100: 61-65, 1983
Ianniello F, Ferri E, Armato E, et al: Carcinosarcoma of the larynx: immunohistochemical study, clinical considerations, therapeutic strategies. Acta Otorhinolaryngol Ital 21: 192-197, 2001
Kitsmaniuk ZD, Volkov I, Demochko VB, et al: Synovial sarcoma of the larynx. Vestn Otorinolaryngol; 2: 61-62, 1985
Kleinasser O: Tumors of the larynx and hypopharynx. Stuttgart Thieme 1988: pp 326-328
Miller LH, Santaella-Latimer L, Miller T: Synovial sarcoma of the larynx. Trans Am Acad Ophtalmol Otolaryngol 80: 448- 451, 1975
Morland B, Cox G, Randall C, et al: Synovial sarcoma of the larynx in a child: case report and histological appearances. Med Pediatr Oncol 23: 64-68, 1994
Pruszczynski M, Manni JJ, Smedt F: Endolaryngeal synovial sarcoma: Case report with immunohistochemical studies. Head Neck 11: 76-80, 1989
Quinn HJ: Synovial sarcoma of the larynx treated by partial laryngectomy. Laryngoscope 94: 1158-1161, 1984
Schneider-Stock R, Onnasch D, Haeckel C, et al: Prognostic significance of p53 gene mutations and p53 protein expression in synovial sarcoma. Virchows Arch 435: 407-412, 1999
Skytting B: Synovial sarcoma: A Scandinavian Sarcoma Group Project. Acta Orthopaedica Scandinavia. Supplementum 291: 1-28, 2000
Skytting BT, Bauer HC, Perfekt R, et al: Ki-67 is stongly prognostic in synovial sarcoma; analysis based on 86 patients from the Scandinavian Sarcoma Group Register. Br J Cancer 80: 1809-1814, 1999
Thompson LD: Diagnostically challenging lesions in head and neck pathology. Eur Arch Otorhinolaryngol 254: 357-366, 1997
Weiss SW, Goldblum JR: Malignant soft tissue tumors of uncertain type. In: Enzinger and Weiss’s Soft Tissue Tumors, 4th ed. Mosby St Louis 2001
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 242
EP 245
PG 4
ER
PT J
AU Szendroi, A
Rusz, A
Szekely, E
Riesz, P
Kelemen, Zs
AF Szendroi, Attila
Rusz, Andras
Szekely, Eszter
Riesz, Peter
Kelemen, Zsolt
TI Renal Tumor Causing Haematuria and Sepsis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE haematuria; pregnancy; kidney tumor; Bellini duct cancer
ID haematuria; pregnancy; kidney tumor; Bellini duct cancer
AB A 28 year old female patient developed hematuria in the 32th week of her pregnancy. She was given antibiotic treatment, since a urinary tract infection was suspected. After delivery symptoms of acute pyelonephritis, then sepsis developed, and conservative therapy had no effect. Ultrasound examination showed unusual renal destruction, so nephrectomy was performed. Surgical intervention revealed the presence of an advanced tumor of the kidney, while histological examination confirmed a Bellini duct carcinoma of the kidney.
C1 [Szendroi, Attila] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1078 Budapest, Hungary.
[Rusz, Andras] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1078 Budapest, Hungary.
[Szekely, Eszter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Riesz, Peter] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1078 Budapest, Hungary.
[Kelemen, Zsolt] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1078 Budapest, Hungary.
RP Szendroi, A (reprint author), Semmelweis University, Department of Urology, H-1078 Budapest, Hungary.
EM atsszendroi@freemail.hu
CR Antonelli A, Portesi E, Cozzoli A, et al: The collecting duct carcinoma of the kidney: a cytogenetical study. Eur Urol 43:680- 685, 2003
Belldegrun A, deKernion JB: Renal tumors In: Campbell’s Urology, 7th ed. Edited by PC Walsh, AB Retik, TA Stamey and ED Vaughan. Philadelphia: WB Saunders Co., vol.3, Chapt 76, pp. 2283-2327, 1998
Cheville JC, Lohse CM, Zincke H, et al: Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma Am J Surg Pathol 27:612-24, 2003
El Fettouh HIA, Cherullo E, El-Jack M, et al: Sporadic renal cell carcinoma in young adults: presentation, treatment and outcome. Urology 60: 806-810, 2002
Kovacs G, Akhtar M, Beckwith BJ, et al: The Heidelberg classification of renal cell tumors. J Path 183:131, 1997
Mejean A, Roupret M, Larousserie F,et al: Is there a place for radical nephrectomy in the presence of metastatic collecting duct, Bellini, carcinoma? J Urol 169:1287-90, 2003
Mickisch GHJ: Rational selection of a control arm for randomised trials in metastatic renal cell carcinoma Eur Urol 43:670-679, 2003
Poel van der H.G, Roukema JA, Horenblas S, et al: Metastectomy in renal cell carcinoma: a multicenter retrospective analysis. Eur Urol 35:197-203, 1999
Romics I, Goepel M: A here es vesedaganatok diagnosztikaja es terapiaja. Akademiai Kiado, 1998
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 246
EP 248
PG 3
ER
PT J
AU Vargas-Gonzalez, R
Solis-Coria, A
AF Vargas-Gonzalez, Roberto
Solis-Coria, Araceli
TI Giant Cell Fibroblastoma in a 3-Year-Old Boy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE tumor; giant cell; giant cell fibroblastoma; dermatofibrosarcoma protuberans
ID tumor; giant cell; giant cell fibroblastoma; dermatofibrosarcoma protuberans
AB Giant cell fibroblastoma (GCF) is a rare soft tissue tumor most often discovered during the first two decades of life. We present a case of a 3-year-old boy with a history of a recurrent lesion in the knee, the tumor growth progressively and enlarged to 2.1 cm in the previous two years before diagnosis. It involved the subcutaneous tissue, had infiltrative borders and extended into the superficial dermis. The tumor was surgically excised with free margins. There was no evidence of local recurrence, and a metastatic workup was negative after 10 years of follow up. We review herein the clinicopathologic features, histogenesis, differential diagnosis and relationship to dermatofibrosarcoma protuberans (DFSP).
C1 [Vargas-Gonzalez, Roberto] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla-Atlixco, 72190 Puebla, Mexico.
[Solis-Coria, Araceli] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla-Atlixco, 72190 Puebla, Mexico.
RP Vargas-Gonzalez, R (reprint author), Hospital Para el Nino Poblano, Department of Pathology, 72190 Puebla, Mexico.
EM soncoy@msn.com
CR Shmookler BM, Enzinger FM: Giant cell fibroblastoma: a peculiar childhood tumor. Lab Invest 46:76- xx, 1982.
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Kholova I, Ryska A, Dedic K: Composite tumor consisting of dermatofibrosarcoma protuberans and giant cell fibroblastoma associated with intratumoral endometriosis. Report of a case. Pathol Res Pract 197:263-7,2001.
Maeda T, Hirose T, Furuya K, et al: Giant cell fibroblastoma associated with dermatofibrosarcoma protuberans: a case report. Mod Pathol 11:491-5,1998.
Fletcher CD: Giant cell fibroblastoma of soft tissue: a clinicopathological and immunohistochemical study. Histopathology 13:499-508,1988.
Weiss SW, Nickoloff BJ: CD 34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 17:1039.1993.
Abdul-Karim W, Evans HL, Silva EG: Giant cell fibroblastoma: a report of three cases. Am J Clin Pathol 83:165-70,1985.
Nguyen CM, Burch JM, Fitzpatrick JE, et al: Giant cell fibroblastoma in a child misdiagnosed as a dermatofibroma. Ped Dermatol 19:28-32,2002.
Goldblum JR: Giant cell fibroblastoma a report of three cases with histologic and immunohistochemical evidence of a relationship to dermatofibrosarcoma protuberans. Arch Pathol Lab Med 120:1052-55,1996.
Beham A, Fletcher CDM: Dermatofibrosarcoma protuberans with areas resembling giant cell fibroblastoma: report of two cases. Histopathology 17:165-7,1990.
Cin PD, Sciot R, De Wever I, et al: Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans. Genes Chromosomes Cancer 15:73,1996.
Terrier-Lacombe MJ, Guillou L, Maire G, et al: Dermatofibrosarcoma protuberans, giant cell fibroblastoma and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data-a study from the French federation of cancer centers sarcoma group. Am J Surg Pathol 27:27- 39,2003.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 249
EP 251
PG 3
ER
PT J
AU Zalatnai, A
AF Zalatnai, Attila
TI Pancreatic Cancer - a Continuing Challenge in Oncology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE pancreatic cancer; risk factors; PanIN; hormones; chemoprevention; review
ID pancreatic cancer; risk factors; PanIN; hormones; chemoprevention; review
AB Pancreatic cancer is still one of the major health problems because of its rising incidence and the modest therapeutic results. The paper surveys the statistical data, the risk factors, the preneoplastic ductal lesions, the hormonal sensitivity, the possible transdifferentiation in the endocrine and exocrine parts and the possibilities for chemoprevention. Hungary is peculiar among the European countries because during the last 50 years the incidence of pancreatic cancer has displayed a 15-fold increase. Apart from smoking, additional risk factors seem to be important, and recently a puzzling association between Helicobacter pylori seropositivity and pancreatic cancer was found. First-degree relatives of patients with pancreatic cancer are also at increased risk of this tumor. The term pancreatic intraepithelial neoplasia (PanIN) seems yet to be established, but the dynamics of these lesions needs to be further elucidated. Several lines of firmly established data indicate the hormonal sensitivity of this tumor, but still an unexplained discrepancy exists between the experimental and the clinical results. In addition to the somatostatin analogs, anti-gastrin vaccine is being tested. The mixed exocrine-endocrine tumors might suggest a real possibility of transdifferentiation between different compartments of the pancreas. Finally, the paper outlines the available data about the possibility of chemoprevention, including the role of cyclooxygenase inhibitors.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
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Anderson KE, Hammons GJ, Kadlubar FF, et al: Metabolic activation of aromatic amines by human pancreas. Carcinogenesis 18: 1085-1092, 1997
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Fenoglio CM, King DW: Somatostatin: an update. Human Pathol 14: 475-479, 1983
Fernandez E, La Vecchia C, Porta M, et al: Trends in pancreatic cancer mortality in Europe, 1955-1989. Int J Cancer 57: 786-792, 1994
Fisher WE, Muscarella P, Boros LG, et al: Gastrointestinal hormones as potential adjuvant treatment of exocrine pancreatic adenocarcinoma. Int J Pancreatol 24: 169-180, 1998
Fisher WE, Doran TA, Muscarella P, et al: Expression of somatostatin receptor subtype 1-5 genes in human pancreatic cancer. J Natl Cancer Inst 90: 322-324, 1998
Fueger BJ, Hamilton G, Raderer M, et al: Effects of chemotherapeutic agents on expression of somatostatin receptors in pancreatic tumor cells. J Nucl Med 42: 1856-1862, 2001
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Gudjonsson B: Survival statistics gone awry: pancreatic cancer, a case in point. J Clin Gastroenterol 35: 180-184, 2002
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Hahn SA, Greenhalf B, Ellis I, et al: BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 95: 214-221, 2003
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Hemminki K, Li X: Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden. Int J Cancer 103: 525-530, 2003
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2003
VL 9
IS 4
BP 252
EP 263
PG 12
ER
PT J
AU Szabo, E
Paska, Cs
Kaposi Novak, P
Schaff, Zs
Kiss, A
AF Szabo, Erzsebet
Paska, Csilla
Kaposi Novak, Pal
Schaff, Zsuzsa
Kiss, Andras
TI Similarities and Differences in Hepatitis B and C Virus Induced Hepatocarcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; hepatocarcinogenesis
ID hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; hepatocarcinogenesis
AB Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant diseases worldwide. Among other environmental factors, hepatitis viruses, as the hepatitis B (HBV) and hepatitis C (HCV) viruses, are to be listed in the etiology of HCC. Both of these viruses cause a wide spectrum of clinical manifestations, ranging from healthy carrier state to acute and chronic hepatitis, cirrhosis and HCC. HBV and HCV are different viruses in structure: HBV contains a DNA genome which replicates through an RNA intermediate and requires an active viral reverse transcriptase (RT) polymerase enzyme, while HCV is an RNA virus which has no RT activity and replicates on the cellular membrane by RNA replication. In this review we discuss how these two biologically diverse viruses use common pathways to induce hepatocarcinogenesis despite their significant structural and viral cycle differences. A summary is also given of several observable common and different features. Direct integration of HBV viral sequences into the host genome increases the genomic instability, which does not occur in HCV infection. However, viral proteins may directly play a significant role in the induction of carcinogenesis by both viruses.
C1 [Szabo, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Paska, Csilla] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Kaposi Novak, Pal] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93., H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 5
EP 11
PG 7
ER
PT J
AU Mehes, K
Kosztolanyi, Gy
AF Mehes, Karoly
Kosztolanyi, Gyorgy
TI Clinical Manifestations of Genetic Instability Overlap One Another
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE genetic instability; cancer-prone diseases; mild errors of morphogenesis; premature centromere division; predisposition to cancer
ID genetic instability; cancer-prone diseases; mild errors of morphogenesis; premature centromere division; predisposition to cancer
AB Cancer syndromes are characteristic associations of specific malignancies with various congenital anomalies. In addition to such diseases, an increased prevalence in general of chromosomal instability, malformations, immunodeficiencies, altered growth and development, and reproductive loss has been observed in both childhood leukemias and solid tumors. The overlap among these congenital disorders suggests their common prenatal, possibly genetic origin and thus the existence of a nonspecific genetic instability leading to various clinical manifestations of disturbancies in cell division. Seeking for related features in family members of a patient with malignancy may be of clinical value in detecting predisposition to cancer.
C1 [Mehes, Karoly] University of Pecs, Department of Medical Genetics and Child Development, Jozsef Attila u. 7, H-7623 Pecs, Hungary.
[Kosztolanyi, Gyorgy] University of Pecs, Department of Medical Genetics and Child Development, Jozsef Attila u. 7, H-7623 Pecs, Hungary.
RP Mehes, K (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7623 Pecs, Hungary.
EM karoly.mehes@aok.pte.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 12
EP 16
PG 5
ER
PT J
AU Ebinger, M
Senf, L
Wachowski, O
Scheurlen, W
AF Ebinger, Martin
Senf, Leonore
Wachowski, Olga
Scheurlen, Wolfram
TI Promoter Methylation Pattern of Caspase-8, P16INK4A, MGMT, TIMP-3, and E-Cadherin in Medulloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE aberrant promoter methylation; medulloblastoma; caspase-8; p16INK4A; MGMT; TIMP-3; CDH1
ID aberrant promoter methylation; medulloblastoma; caspase-8; p16INK4A; MGMT; TIMP-3; CDH1
AB Methylation of promoter regions of CpG-rich sites is an important mechanism for silencing of tumor suppressor genes (TSG). To evaluate the role of tumor suppressor genes caspase-8 (CASP8), TIMP-3, E-cadherin (CDH1), p16INK4A, and MGMT in medulloblastoma tumorigenesis, 51 medulloblastomas (46 primary tumor specimens, 5 cell lines) were screened for methylation of promoter linked CpG-islands. For CASP8, we examined the 5' UTR region that has been shown to be associated with expression of CASP8. As detected by methylation specific PCR, methylation rate was low for TIMP-3 (3% of tumor samples; 1/5 cell lines), for MGMT (0% of tumor samples; 1/5 cell lines), for p16INK4A (2% of tumor samples; 2/5 cell lines) and for CDH1 (8% of tumor samples; 1/4 cell lines). CASP8, however, was methylated in 90% of tumor samples and 4/5 cell lines examined. Screening other tumor entities for CASP8 methylation, we found a similarly high level in 6 neuroblastoma cell lines in contrast to 5 osteosarcoma-, 4 Ewing's sarcoma- and 6 non-embryonic tumor cell lines without any increased promoter methylation. From our results we conclude that methylation of the CASP8 5' UTR region may play a role in inactivation of CASP8 in neural crest tumors.
C1 [Ebinger, Martin] Institute of Pathology, Department of Molecular PathologyTubingen, Germany.
[Senf, Leonore] Cnopf'sche Kinderklinik, St. Johannis-Muhlgasse 19, 90419 Nurnberg, Germany.
[Wachowski, Olga] University Hospital Gießen, Zentrum fur Kinderheilkunde und JugendmedizinGiessen, Germany.
[Scheurlen, Wolfram] Cnopf'sche Kinderklinik, St. Johannis-Muhlgasse 19, 90419 Nurnberg, Germany.
RP Scheurlen, W (reprint author), Cnopf'sche Kinderklinik, 90419 Nurnberg, Germany.
EM wolfram.scheurlen@nbg.diakonieneuendettelsau.de
CR Bachman KE, Herman JG, Corn PG et al: Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggests a suppressor role in kidney, brain, and other human cancers. Cancer Res 59: 798-802, 1999.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 17
EP 21
PG 5
ER
PT J
AU Raso, E
Meszaros, L
Albini, A
Timar, J
AF Raso, Erzsebet
Meszaros, Livia
Albini, Adriana
Timar, Jozsef
TI A WT1 Expressing Metastatic Human Kaposi Sarcoma Xenograft Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kaposi sarcoma; xenograft model; WT1 expression; metastasis
ID Kaposi sarcoma; xenograft model; WT1 expression; metastasis
AB We have established a non-metastatic and a metastatic human Kaposi sarcoma (KS) xenograft model in SCID mice by injecting KS-Imm cells subcutaneously and intrasplenically, respectively. KS-Imm cells expressed endothelial markers, CD34 and vWF in vivo. Futhermore, we have shown that these cells express all the splice variants of the WT1 gene and WT1wt protein in vitro and in vivo detected by nested PCR and immunohistochemistry. WT1 expression in the peripheral blood was only detectable in case of metastatic KS model suggesting it as a molecular marker of progression.
C1 [Raso, Erzsebet] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Meszaros, Livia] National Institute of Oncology, Department of Diagnostic PathologyBudapest, Hungary.
[Albini, Adriana] Istituto Nazionale per la Ricerca sul CancroGenova, Italy.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Bais C, van Geelen A, Eroles P et al.: Kaposi’s sarcoma associated herpesvirus G protein-coupled receptor importalized human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell 3:131-143, 2003
Montaner S, Sodhi A, Molinolo A et al.: Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3: 23-36, 2003
Moses AV, Jarvis MA, Raggo C et al: Kaposi’s sarcoma-associatd herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the tansformation of endothelial cells. J Virol 76:8383-8399, 2002
Folpe AL, Veikkola T, Valtola R, Weiss SW: Vascular endothelial growth factor receptor-3, VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi’s sarcoma, kaposiform and dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol 13:180-185,2000
Jussila L, Valtola R, Partanen TA et al: Lymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res 58: 1599-
04, 1998 6. Kahn HJ, Bailey D and Marks A: Monoclonal antibody D2-40, a new maker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol 15: 434-440, 2002
Simonart T, Degraef C, Heenen M et al: Expression of the fibroblast/ macrophage marker 1B10 by spindle cells in Kaposi’s sarcoma lesions and by Kaposi’s sarcoma-derived tumor cells. J Cutan Pathol 29: 72-78, 2002
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Gehling UM, Ergun S, Schumacher U, Wagener Ch et al: In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 95:3106-3112, 2000
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Rafii S, Lyden D, Benezra R et al: Vascular and hamatopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2:826-835, 2002
Albini A, Paglieri I, Orengo G et al: The beta core fragment of human choriogonadotrophin inhibits growth of Kaposi Sarcoma derived cells and a new immortalized Kaposi sarcoma cell line. AIDS 11:713-721, 1997
Lunardi-Iskandar Y, Gill P, Lam VH et al: Isolation and characterization of an immortal neoplastic cell, KS Y-1, from AIDS-Associated Kaposi’s sarcoma. J Natl Cancer Inst 87: 974-949, 1995
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Ellisen LW, Carlesso N, Cheng T et al: The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J 20:1897-1909, 2001
Magyarosy E, Varga N, Timar J, Raso E. Follow-up of minimal residual disease in acute childhood lymphoblastic leukemia by WT1 gene expression in the peripheral blood: The Hungarian experience. Pediatric Haematol Oncol 20:65-74,2003
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 22
EP 25
PG 4
ER
PT J
AU Wu, Q
Suo, Z
Risberg, B
Karlsson, GM
Villman, K
Nesland, MJ
AF Wu, Qinghua
Suo, Zhenhe
Risberg, Bjorn
Karlsson, G Mats
Villman, Kenneth
Nesland, M Jahn
TI Expression of Ephb2 And Ephb4 in Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EphB2; EphB4; breast carcinoma; RT-PCR; immunohistochemistry
ID EphB2; EphB4; breast carcinoma; RT-PCR; immunohistochemistry
AB Eph receptor tyrosine kinases and their cell-surfacebound ligands, the ephrins, play key roles in diverse biological processes. Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors (with five corresponding ephrinA ligands) and six EphB receptors (with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, EphB receptors and ephrinB ligands are later proved to be crucial regulators of vasculogenesis and embryogenesis. More studies indicate that Eph receptors are involved in angiogenesis and tumorigenesis. This study aimed to investigate the expression of EphB2 and EphB4 in breast carcinomas. Semiquantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of EphB2 and EphB4. Clinicopathological and survival correlations were statistically analyzed in a series of 94 breast carcinomas, 9 normal specimens and 4 breast carcinoma cell lines. 1(1%), 16(17%), 29(31%), 48(51%) of the 94 tumors were negative, weak, moderate and strong EphB2 protein expression, respectively. 6(6%), 27(29%), 28(30%), 33(35%) of the tumors were negative, weak, moderate and strong EphB4 expression, respectively. Both EphB2 and EphB4 RTPCR products could be detected in all specimens. Increased EphB2 protein expression was negatively associated with overall survival, and there was a trend that increased EphB2 protein expression was correlated with shorter disease free survival, while EphB4 protein expression was associated with histological grade and stage. EphB4 membrane staining was increased with S phase fraction and associated with DNA aneuploidy. These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers.
C1 [Wu, Qinghua] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, N-0310 Oslo, Norway.
[Suo, Zhenhe] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, N-0310 Oslo, Norway.
[Risberg, Bjorn] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, N-0310 Oslo, Norway.
[Karlsson, G Mats] Orebro Medical Center Hospital, Department of PathologyOrebro, Sweden.
[Villman, Kenneth] Orebro Medical Center Hospital, Department of OncologyOrebro, Sweden.
[Nesland, M Jahn] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, N-0310 Oslo, Norway.
RP Suo, Z (reprint author), The Norwegian Radium Hospital, University of Oslo, Department of Pathology, N-0310 Oslo, Norway.
EM zhenhes@labmed.uio.no
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Wang HU, Chen ZF, Anderson DJ: Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93: 741- 753, 1998.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 26
EP 33
PG 8
ER
PT J
AU Mazur, G
Wozniak, Z
Wrobel, T
Maj, J
Kuliczkowski, K
AF Mazur, Grzegorz
Wozniak, Zdzislaw
Wrobel, Tomasz
Maj, Joanna
Kuliczkowski, Kazimierz
TI Increased Angiogenesis in Cutaneous T-cell Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; microvessel density; cutaneous T-cell lymphoma; mycosis fungoides
ID angiogenesis; microvessel density; cutaneous T-cell lymphoma; mycosis fungoides
AB Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms derived from skin-homing T cells. CTCL behave similarly to indolent B-cell lymphomas. There is increasing evidence that angiogenesis may be important in lymphoproliferative disorders. The aim of the study was to evaluate microvessel density (MVD) as a parameter of tumor angiogenesis measured by the expression of CD34 in the skin samples in CTCL patients. Formaldehyde-fixed, paraffin-embedded skin tumor biopsy specimens from 25 patients (16 men, 9 women) with CTCL (mycosis fungoides), and 8 skin samples from healthy volunteers were analysed. The preparations were stained with haematoxylin and eosin, and evaluated histopathologically. Staining for endothelial cells with monoclonal antibody against CD34 revealed a mean number of 134 dots per mm2 for CTCL and 106 dots/mm2 for controls; the difference was statistically significant (p=0.0388). Our study shows a higher number of microvessels in primary CTCL compared with normal skin. Microvascular endothelial cells have become an important target in cancer therapy. Increased MVD in the skin of CTCL patients indicate that angiogenesis may play a role in the growth of CTCL, and raises the possibility of using angiogenesis inhibitors in CTCL therapy.
C1 [Mazur, Grzegorz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 4, 50-367 Wroclaw, Poland.
[Wozniak, Zdzislaw] Wroclaw Medical University, Department of PathologyWroclaw, Poland.
[Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 4, 50-367 Wroclaw, Poland.
[Maj, Joanna] Wroclaw Medical University, Department of Dermatology, Venereology and AllergologyWroclaw, Poland.
[Kuliczkowski, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 4, 50-367 Wroclaw, Poland.
RP Mazur, G (reprint author), Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 50-367 Wroclaw, Poland.
EM grzegmaz@hemat.am.wroc.pl
CR Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27-31, 1995
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Mangi MH, Newland AC: Angiogenesis and angiogenic mediators in haematological malignancies. Br J Haematol 111: 43- 51, 2000
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Ridell B, Norrby K: Intratumoral microvascular density in malignant lymphomas of B-cell origin. APMIS 109: 66-72, 2001
Salven P, Teerenhovi L, Joensuu H: A high pretreatment serum basic fibroblast growth factor concentration is an independent predictor of poor prognosis in non-Hodgkin lymphoma. Blood 94: 3334-3339, 1999
Schaerer L, Hess-Schmid M, Mueller B, et al: Angiogenesis in cutaneous lymphoproliferative disorders: microvessel density discriminates between cutaneous B-cell lymphomas and B-cell pseudolymphomas. Am J Dermatopathol 22: 140-143, 2000
Siegel RS, Pandolfino T, Guitart J, et al: Primary cutaneous Tcell lymphoma: review and current concepts. J Clin Oncol 18: 2908-2925, 2000
Vacca A, Moretti S, Ribatti D et al: Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9. Eur J Cancer 33: 1685-1692, 1997
Vacca A, Ribatti D, Roncali L, Dammacco F: Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies. Leuk Lymphoma 20: 27-38, 1995
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Willemze R, Kerl H, Sterry W, et al: EORTC classification for primary cutaneous lymphomas: a proposal from the cutaneous lymphoma study group of the European Organization for Research and Treatment. Blood 90: 354-371,1997
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 34
EP 36
PG 3
ER
PT J
AU Amirghofran, Z
Monabati, A
Gholijani, N
AF Amirghofran, Zahra
Monabati, Ahmad
Gholijani, Naser
TI Androgen Receptor Expression in Relation to Apoptosis and the Expression of Cell Cycle Related Proteins in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostate carcinoma; androgen receptor; apoptosis; p53; bcl-2; bax; Ki-67
ID prostate carcinoma; androgen receptor; apoptosis; p53; bcl-2; bax; Ki-67
AB The expression of several genes involved in the regulation of cell cycle and apoptosis may be regulated via the androgen receptor (AR) in the prostate. AR may have a role in the prognosis of prostatic carcinoma. The aim was to examine AR expression status and its relationship with markers of proliferation, apoptosis and cell cycle control in prostate cancer. Expression of AR, bcl-2, bax, Ki-67 and p53 was examined in paraffin-embedded tissues from 50 cases of prostate carcinoma by immunohistochemistry and evaluated using an index of staining. Detection of apoptotic cells was performed by TUNEL method. Correlation between AR expression and apoptosis, proliferation index, bcl-2, bax and p53 and also clinicopathological parameters including stage, pathological grade and Gleason score were determined. AR expression was observed in all cases with mean expression of 81%+/-15 and mean staining index of 141+/-65. No correlation was found between AR expression and apoptosis detected in patients. The mean AR staining index was 170+/-72 in bcl-2 positive tumors versus 120+/-53 in bcl-2 negative tumors showing a significant association between AR and bcl-2 expression (p=0.015). AR expression also showed a significant association with bcl-2/bax ratio (r=0.321, p=0.023) and Ki-67 proliferation staining index (r=0.396, p=0.004). Although a significant correlation between Ki-67 and p53 with differentiation status of the tumors was observed (p<0.004) no correlation was found with AR. AR expression showed no prognostic value regarding its correlation with stage and differentiation status of the prostate carcinoma. However, its significant correlation with Ki-67 and bcl-2 that are markers of cell survival suggest its contribution to tumor cell progression.
C1 [Amirghofran, Zahra] Medical School, Shiraz University of Medical Sciences, Department of Immunology, 71345-1798 Shiraz, Iran.
[Monabati, Ahmad] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Gholijani, Naser] Medical School, Shiraz University of Medical Sciences, Department of Immunology, 71345-1798 Shiraz, Iran.
RP Amirghofran, Z (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, 71345-1798 Shiraz, Iran.
EM amirghz@sums.ac.ir
CR Buttyan R, Shabsigh A, Perlman H, Colombel M. Regulation of Apoptosis in the Prostate Gland by Androgenic Steroids. Trends Endocrinol Metab 10:47-54, 1999
Chang C, Saltzman A, Yeh S et al.: Androgen receptor: an overview. Crit Rev Eukaryot Gene Exp 5: 97-125, 1995
Eder IE, Culig Z, Putz T et al.: Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur Urol 40:241-51, 2001
Klocker H, Culig Z, Eder IE et al: Mechanism of androgen receptor activation and possible implications for chemoprevention trials. Eur Urol 35: 413-419, 1999.
Kyprianou N, Isaacs JT: Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122: 552-562, 1988
Gelmann EP. Molecular biology of the androgen receptor. J Clin Oncol 20: 3001-3015, 2002
Feng Z, Joos HJ, Vallan C et al: Apoptosis during castrationinduced regression of the prostate is Fos dependent. Oncogene 19: 17: 2593-600, 1998
Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol 168: 9-12, 2002
Culig Z, Klocker H, Bartsch G et al: Androgen receptors in prostate cancer. J Urol 170: 1363-1369 2003.
Culig Z, Hobisch A, Erdel M et al: Studies on androgen receptor mutations and amplification in human prostatecancer. Methods Mol Med 81: 267-275, 2003
Sadi MV, Barrack ER: Image analysis of androgen receptor immunostaining in metastatic prostate cancer. Heterogeneity as a predictor of response to hormonal therapy. Cancer 15: 71: 2574-2580, 1993
Miyamoto KK, McSherry SA, Dent GA et al.: Immunohistochemistry of the androgen receptor in human benign and malignant prostate tissue. J Urol 149:1015-1019, 1993
de Winter JA, Trapman J, Brinkmann AO et al: Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry. J Pathol 160: 329-332, 1990
Shaffer DR, Scher HI. Prostate cancer: a dynamic illness with shifting targets. Lancet Oncol 4: 407-414, 2003
Magi-Galluzzi C, Xu X, Hlatky L et al: Heterogeneity of androgen receptor content in advanced prostate cancer. Mod Pathol 10: 839-845, 1997
Sweat SD, Pacelli A, Bergstralh EJ et al: Androgen receptor expression in prostatic intraepithelial neoplasia and cancer. J Urol 161: 1229-1232, 1999
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Kolar Z, Murray PG, Madarova J et al: Nuclear receptors in early hormone refractory prostate cancer and their relationship to apoptosis-related proteins. Neoplasma 49:172-177, 2002
Fizazi K, Martinez LA, Sikes CR et al: The association of p21, WAF-1/CIP1, with progression to androgen-independent prostate cancer. Clin Cancer Res 8: 775-781, 2002
Tanji N. Yokoyama M. Sagamoto T et al: Apoptosis in prostatic adenocarcinoma; A study of relationship to Ki-67 and bcl-2 protein expression. Anticancer Res 18:1111-1116, 1998
Kaltz-Wittmer C, Klenk U, Glaessgen A et al: FISH analysis of gene aberrations, MYC, CCND1, ERBB2, RB, and AR, in advanced prostatic carcinomas before and after androgen deprivation therapy. Lab Invest 80: 1455-1464, 2000
Baretton GB, Klenk U, Diebold J et al: Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression. Br J Cancer 80: 546- 555, 1999
Cadwell C, Zambetti GP: The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth. Gene 17: 15-30, 2001
Brooks JD, Bova GS, Ewing CM et al: An uncertain role for p53 gene alterations in human prostate cancers. Cancer Res 56: 3814-3822. 1996
Navone NM, Troncoso P, Pisters LL, et al.: p53 protein accumulation and gene mutation in the progression of human prostate carcinoma. J Natl Cancer Inst 85: 1657-1669, 1993
Aprikian AG, Sarkis AS, Fair WR et al: Immunohistochemical determination of p53 protein nuclear accumulation in prostatic adenocarcinoma. J Urol 151: 1276-1280, 1994
Bargonetti J, Manfredi JJ. Multiple roles of the tumor suppressor p53. Curr Opin Oncol 14: 86-91, 2002
Howell SB. Resistance to apoptosis in prostate cancer cells. Mol Urol 4: 225-229, 2000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 37
EP 41
PG 5
ER
PT J
AU Esik, O
Emri, M
Szakall, Sz
Herzog, H
Safrany, G
Lengyel, E
Boer, A
Liszkay, G
Tron, L
Lengyel, Zs
Repa, I
AF Esik, Olga
Emri, Miklos
Szakall, Szabolcs
Herzog, Hans
Safrany, Geza
Lengyel, Erzsebet
Boer, Andras
Liszkay, Gabriella
Tron, Lajos
Lengyel, Zsolt
Repa, Imre
TI PET Identifies Transitional Metabolic Change in the Spinal Cord Following a Subthreshold Dose of Irradiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiotherapy; spinal cord; positron emission tomography; [18F]fluorodeoxyglucose; [11C]methionine; [15O]butanol; radiobiology
ID radiotherapy; spinal cord; positron emission tomography; [18F]fluorodeoxyglucose; [11C]methionine; [15O]butanol; radiobiology
AB Positron emission tomographic (PET) investigations were performed to obtain in vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy2), with [18F]fluorodeoxyglucose (FDG), [11C]methionine and [15O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [15O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [11C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [11C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury.
C1 [Esik, Olga] University of Pecs, Department of Oncology, Edesanyak utja 17., H-7624 Pecs, Hungary.
[Emri, Miklos] University of Debrecen, PET CenterDebrecen, Hungary.
[Szakall, Szabolcs] University of Debrecen, PET CenterDebrecen, Hungary.
[Herzog, Hans] Research Center, Institute of Medicine, PET LaboratoryJulich, Germany.
[Safrany, Geza] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato IntezetBudapest, Hungary.
[Lengyel, Erzsebet] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Boer, Andras] National Institute of Oncology, Department of Head and Neck SurgeryBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Tron, Lajos] University of Debrecen, PET CenterDebrecen, Hungary.
[Lengyel, Zsolt] University of Debrecen, PET CenterDebrecen, Hungary.
[Repa, Imre] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
RP Esik, O (reprint author), University of Pecs, Department of Oncology, H-7624 Pecs, Hungary.
EM olga.esik@aok.pte.hu
CR Jones A: Transient radiation myelopathy, with reference to Lhermitte’s sign of electrical paraesthesia). Br J Radiol 37:727-744, 1964
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Ang KK, Jiang G-L, Feng Y, et al: Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50:1013- 1020, 2001
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Lipinski B, Herzog H, Rota Kops E, et al: Expectation maximization reconstruction of positron emission tomography images using anatomical magnet resonance information. IEEE Trans Med Imaging 16:129-136, 1997
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 42
EP 46
PG 5
ER
PT J
AU , E
Celikel, C
Gulluoglu, B
AF , Eren
Celikel, Cigdem
Gulluoglu, Bahadir
TI Neuroendocrine Differentiation in Gastric Adenocarcinomas; Correlation with Tumor Stage and Expression of VEGF and p53
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric adenocarcinoma; neuroendocrine; p53; VEGF
ID Gastric adenocarcinoma; neuroendocrine; p53; VEGF
AB Studies on neuroendocrine differentiation (NED) in conventional gastric adenocarcinomas and its significance on tumor behavior are limited. Our aim was to search for the expression of neuroendocrine differentiation in conventional gastric adenocarcinomas and correlate it with tumor type, stage and expression of VEGF and p53. Forty-two gastrectomy specimens with gastric adenocarcinoma were stained with chromogranin A to detect neuroendocrine differentiation and 45% of the cases were found to be NED (+). No significant correlation was found between NED and tumor type. However, NED was more frequent in advanced stage cases independently of tumor type. VEGF expression was also considerably more frequent in NED (+) tumors compared to NED (-) ones (84% vs. 56%). Moreover, we found a significant correlation between NED and the presence of lymph node metastases. P53 expression in NED (+) tumors was 68%. There was no significant correlation between VEGF and p53 in NED (+) cases. In conclusion, neuroendocrine differentiation is a frequent finding in conventional gastric adenocarcinomas, and although it does not seem to play a specific role in tumor progression, it seems that neuroendocrine cells are one of the factors contributing to angiogenesis by expressing VEGF, especially in advanced stage cases, affecting the incidence of lymph node metastases. Further studies with larger series should be performed to confirm this observation.
C1 [, Eren] Marmara University, School of Medicine, Department of Pathology, Bagdat Cad. 277-1 Dostlar apt. Daire 2, Caddebostan, 34728 Istanbul, Turkey.
[Celikel, Cigdem] Marmara University, School of Medicine, Department of Pathology, Bagdat Cad. 277-1 Dostlar apt. Daire 2, Caddebostan, 34728 Istanbul, Turkey.
[Gulluoglu, Bahadir] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
RP , E (reprint author), Marmara University, School of Medicine, Department of Pathology, 34728 Istanbul, Turkey.
EM fyeren@superonline.com
CR Allen FJ, Van Velden DJ, Heyns CF: Are neuroendocrine cells of practical value as an independent prognostic parameter in prostate cancer? Br J Urol 75: 751-754, 1995
Blumenfeld W, Chandhoke D, Jageman P: Neuroendocrine differentiation in gastric adenocarcinomas. An immunohistochemical study. Arch Pathol Lab Med 120: 478-481, 1996
Bostwick DG, Qion J, Pacelli A, et al: Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and survival. J Urol 168: 1204-1211, 2002
Hamilton K, Chiappori A, Olson S, et al: Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma. Mod Pathol 13: 475-481, 2000
Helge L, Waldum, Brenna E, Sandvik A: Relationship of ECL cells and gastric neoplasia. Yale J Biol Med 71: 325-335, 1998
Hiroshima K, Iyoda A, Shibuya K, et al: Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung. Ann Thorac Surg 73: 1732-1735, 2002
Indinnimeo M, Cichini C, Memeo L, et al: Correlation between chromogranin A expression and pathological variables in human colon carcinoma. Anticancer Res 22: 395-398, 2002
Kyokane K, Ito M, Sato Y, et al: Expression of bcl-2 and p53 correlates with the morphology of gastric neoplasia. J Pathol 184: 382-389, 1998
Maehara Y, Kabashima A, Koga T, et al: Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma. Surgery 128: 408-416, 2000
Maeda K, Kong SM, Onoda N, Ogawa M: Expression of p53 and vascular endothelial growth factor associated with tumor angiogenesis and prognosis in gastric adenocarcinoma. Oncology 55: 594-599, 1998
Miremadi A, Pinder SE, Lee AH, et al: Neuroendocrine differentiation and prognosis in breast carcinoma. Histopathology 40: 211-214, 2002
Ooi A, Hayashi H, Katsuda S, et al: Gastric adenocarcinoma cells with endocrine differentiation show no evidence of proliferation. Hum Pathol 23: 736-741, 1992
Ooi A, Mai M, Ogino T, et al: Endocrine differentiation of gastric carcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. Cancer 62: 1096-1104, 1998
Park JG, Choe GY, Helmon LJ, et al: Chromogranin-A expression in gastric and colon cancer tissues. Int J Cancer 51: 189- 194, 1992
Qvigstad G, Arne K, Sandvik A, et al: Detection of chromogranin A in human gastric adenocarcinomas using a sensitive immunohistochemical technique. Histochemical J 32: 551-556, 2000
Saito H, Tujitani S, Ikeguchi M, et al: Neoangiogenesis and relationship to nuclear p53 accumulation and vascular endothelial growth factor expression in advanced gastric carcinoma. Oncology 57: 164-172, 1999
Waldum HL, Brenna E, Sandvik A: Relationship of ECL cells and gastric neoplasia. Yale J Biol Med 71: 325-335, 1998
Waldum HL, Aase S, Kuetnoi I: Neuroendocrine differentiation in human gastric carcinoma. Cancer 83: 435-444, 1998
Wu MS, Shen OJ, Sheu JC: Overexpression of mutant p53 and C-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma. J Gastroenterol Hepatol 13: 305- 310, 199
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 47
EP 51
PG 5
ER
PT J
AU Pal, J
Marczinovits, I
Hudecz, F
Toth, KG
Mezo, G
Molnar, J
Nemeth, P
AF Pal, Jozsef
Marczinovits, Ilona
Hudecz, Ferenc
Toth, K Gabor
Mezo, Gabor
Molnar, Janos
Nemeth, Peter
TI Modeling of Main Characteristics of Bullous Pemphigoid Antigen-2 (BPAG2) Peptide Structure in Serological Recognition by Autoantibodies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE carrier effect; BPAG2 epitope; autoantibodies; immunological recognition; cross-reaction
ID carrier effect; BPAG2 epitope; autoantibodies; immunological recognition; cross-reaction
AB The serum level of autoantibodies against autoantigens of the bullous pemphigoid peptides 1 and 2 (BPAG1 and BPAG2) is a relevant diagnostic marker. Twelve representative sera of BP were tested against the RSILPYGDSMDRIEKDRLQMAP amino acid sequence that is an epitope fragment of the NC16A domain of BPAG2 (AC Q02802; 507-528) to find the most suitable antigenic form for specific detection of autoantibodies of BP patients’ sera by quantitative ELISA system. The antigenic epitope sequence was presented as an antigen in a carrier free form of dimeric peptide (BP22), dimeric peptide fused to glutathione S-transferase (GST-BP22) or dimeric peptide chemically conjugated to polyLys(Ser-DL-Alam) (SAK-BP22). The intensity of ELISA reaction was highest against the recombinant fusion antigen GSTBP22; the chemically conjugated SAK-BP22 performed less well than the free dimeric form of the peptide. In the case of the GST-BP22 antigen, the (GST-BP22)-(GST)492nm optical density values were determined. There was no significant difference between the mean ODs of the GST-BP22 and the SAK-BP22 (0.888 vs. 0.892, p= 0.9726). Conjugating the epitope peptide with the synthetic carrier SAK was advantageous, as it abrogated cross-reactivity with GST carrier protein. Consequently, the SAKBP22 conjugate appears to be the most reliable assay component, avoiding cross-reactivity with GST and simplifying the detection and evaluation of BP autoantibodies in routine ELISA diagnostic system.
C1 [Pal, Jozsef] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u 12., H-7643 Pecs, Hungary.
[Marczinovits, Ilona] University of Szeged, Department of PhysiologySzeged, Hungary.
[Hudecz, Ferenc] Eotvos Lorand University, Hungarian Academy of Sciences, MTA-ELTE Research Group of Peptide ChemistryBudapest, Hungary.
[Toth, K Gabor] University of Szeged, Department of Medical ChemistrySzeged, Hungary.
[Mezo, Gabor] Eotvos Lorand University, Hungarian Academy of Sciences, MTA-ELTE Research Group of Peptide ChemistryBudapest, Hungary.
[Molnar, Janos] University of Szeged, Department of PhysiologySzeged, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u 12., H-7643 Pecs, Hungary.
RP Nemeth, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM peter.nemeth@aok.pte.hu
CR Dopp R, Schmidt E, Chimanovitch I et al: IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in bullous pemphigoid: Serum levels of these immunoglobulins reflect disease activity. J Am Acad Dermatol 42:577-583, 2000
Hancock DC, O’Relly NJ, Evan GI: Synthetic peptides in biochemical research. Mol Biotechnol 4:73-86, 1995
Hudecz F, Pimm MV, Rajnavolgyi E et al: Carrier design: New generation of polycationic branched polypeptides containing OH groups with prolonged blood survival and diminished in vitro cytotoxicity. Bioconjug Chem 10:781-790, 1999
Hudecz F: Manipulation of epitope function by modification of peptide structure. A minireview. Biologicals 29:197-207, 2001
Husz S, Kiss M, Molnar K et al: Development of a system for detection of circulating antibodies against hemidesmosomal proteins in patients with bullous pemphigoid. Arch Dermatol Res 292:217-224, 2000
Laczko I, Vass E, Toth G K et al: Conformational consequences of coupling bullous pemphigoid antigenic peptides to glutathione- S-transferase and their diagnostic significance. J Pept Sci 6:378-386, 200.
Marczinovits I, Somogyi C, Patthy A et al: An alternative purification protocol for producing hepatitis B virus X antigen on a preparative scale in Escherichia coli. J Biotechnol 56:81- 88, 1997
McCauliffe DP, Yin H, Wang LX, Lucas L: Autoimmune sera react with multiple epitopes on recombinant 52 and 60 kDa Ro(SSA, proteins. J Rheumatol 21:1073-1080, 1994
Molnar J, Marczinovits I, Kiss M et al: Recombinant antigens by fusion of antigenic epitopes to a GST partner. In: Stability and Stabilization of Biocatalysts, Eds: Ballesteros A, Plou FJ, Iborra JL and Halling PJ). Prog Biotechnol 15:691-696, 1998
Nakatani C, Muramatsu T and Shirai T: Immunoreactivity of bullous pemphigoid, BP, autoantibodies against the NC16A and Cterminal domains of the 180 kDa BP antigen, BP180): immunoblot analysis and enzyme-linked immunosorbent assay using BP180 recombinant proteins. Br J Dermatol 139:365-370, 1998
Zillikens D, Mascaro JM, Rose PA et al: A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Invest Dermatol 109:679-683, 1997
Zillikens D, Rose P A, Balding S D et al: Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies. J Invest Dermatol 109:573-579, 1997
Wesierska-Gadek J, Lindner H, Hitchman E et al: Anti-SLA seropositive autoimmune hepatitis sera recognize distinct subunits of glutathione S-transferase: high prevalence of the Ya autoantigen. Cell Mol Biol 48:301-307, 2002
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 52
EP 56
PG 5
ER
PT J
AU Brittig, F
Ajtay, E
Jakso, P
Kelenyi, G
AF Brittig, Ferenc
Ajtay, Elvira
Jakso, Pal
Kelenyi, Gabor
TI Follicular Dendritic Reticulum Cell Tumor Mimicking Inflammatory Pseudotumor of the Spleen
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Follicular dendritic reticulum cells
ID Follicular dendritic reticulum cells
AB In the course of a routine clinical check up of the 54 year old male a splenic well circumscribed tumor like mass of 12 cm in diameter was discovered. Splenectomy with removal of splenic hilar lymph nodes and liver wedge biopsy were performed. Four years later the patient is symptom free. In the removed spleen the tumor like lesion showed a pattern consistent with the diagnosis of inflammatory pseudotumor. However, besides lymphocytes, plasma cells, macrophages, eosinophils and myofibroblasts a high number of slightly polymorphic, frequently binucleated cells positive for CD21 and CD23 were seen. These cells which were scattered or formed smaller or larger groups and fascicles were considered to represent follicular dendritic reticulum cells (FDRCs) and the lesion a FDRC tumor. Flow cytometric DNA ploidy analysis showed a hyperdiploid cell population inside the tumor like lesion. Besides FDRC tumors of high and of intermediate malignancy the present case may represent a low grade type of moderate proliferation activity. The FDRCs of the lesion and a few smaller spindle cells were EBER positive indicative of the presence of EBV. No EBER positive cells were seen in the uninvolved spleen.
C1 [Brittig, Ferenc] County Hospital, Department of PathologyVeszprem, Hungary.
[Ajtay, Elvira] County Hospital, Department of Internal MedicineVeszprem, Hungary.
[Jakso, Pal] University of Pecs, Department of Pathology, Szigeti ut 12., H-7624 Pecs, Hungary.
[Kelenyi, Gabor] University of Pecs, Department of Pathology, Szigeti ut 12., H-7624 Pecs, Hungary.
RP Kelenyi, G (reprint author), University of Pecs, Department of Pathology, H-7624 Pecs, Hungary.
CR Al-Nafussi A, Wong NACS: Intraabdominal spindle cell lesions: a review and practical aids to diagnosis. Histopath 38: 387-402, 2001
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Arber DA, Weiss LM, Chang KL: Detection of Epstein-Barr virus in inflammatory pseudotumor. Semin Diagn Pathol 15: 155-160, 1998
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Biselli R, Boldrini R, Ferlini C, et al: Myofibroblastic tumors: neoplasias with divergent behaviour, ultrastructural and flow cytometric analysis. Pathol Res Pract 195: 619-632, 1999
Biselli R, Ferlini C, Fattorossi A, et al.: Inflammatory myofibroblastic tumor, inflammatory pseudotumor): DNA flow cytometric analysis of nine pediatric cases. Cancer 77: 778-784, 1996
Bofill M, Akbar AN and Amiot PL: Follicular dendritic cells share a membrane-bound protein with fibroblats. J Pathol 191: 217-226, 2000
Chan JKC, Tsang WYW, Ng CS: Follicular dendritic cell tumor and vascular neoplasm complicating hyaline-vascular Castleman’s disease. Am J Surg Pathol 18: 517-525, 1994
Chan JKC, Fletcher CDM, Nayler SJ et al: Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting malignant potential higher than currently recognized. Cancer 79: 294-313, 1997
Cheuk W, Woo PCY, Yuen KY, et al: Intestinal inflammatory pseudotumor with regional lymph node involvement: identification of a new bacterium as the aetiological agent. J Pathol 192: 289-292, 2000
Cheuk W, Chan JKC, Shek TWH, Chang JH, et al: Inflammatory pseudotumor-like follicular dendritic cell tumor. Am J Surg Pathol 25: 721-731, 2000
Coffin CM, Humprey PA, Dehner LP: Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological review. Semin Diagn Pathol 15: 85-101, 1998
Coffin CM, Watterson J, Priest JR, et al: Extrapulmonary inflammatory myofibroblastic tumor, inflammatory pseudotumor): a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 19: 859-872, 1995
Dehner LP: The enigmatic inflammatory pseudotumors: the current state of our understanding, or misunderstanding. J Pathol 192: 277- 279. 2000
Dominis M, Dzebro S, Kusic B, et al: Inflammatory pseudotumor of the spleen. Acta Cytol 42:1053-1056, 1998
Gomez-Roman JJ, Sanchez-Velasco P, Ocejo-Vinyals G, et al: Human herpesvirus-8 genes are expressed in pulmonary inflammatory myofibroblastic tumor, inflammatory pseudotumor). Am J Surg Pathol 25: 624-629, 2001
Jones D, Jorgensen JL, Shahsafaci A, Dorfman DM: Characteristic proliferations of reticular and dendritic cells in angioimmunoblastic lymphoma. Am J Surg Pathol 22: 956-964, 1998
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Moran CA, Suster S, Abondanzo SL: Inflammatory pseudotumor of lymph nodes: a study of 25 cases with emphasis on morphological heterogeneity. Hum. Pathol 28: 332-338, 1997
Noguchi H, Kondo H, Shiraiwas M, et al.: Inflammatory pseudotumor of the spleen: a case report. Jpn J Clin Oncol 30: 190-203, 2000
Overton WR, Catalano E and McCoy P: Method to make paraffinembedded breast and lymph node tissue mimic fresh tissue in DNA analysis. Cytometry 26: 166-171, 1996
Pileri SA, Grogan TM, Harris NL, et al: Tumors of histiocytes and accessory dendritic cells: an immunohistochemical approach to classifcation from the International Lymphoma Study Group based on 61 cases. Histopathology 41: 1-29, 2000
Radhi J, Hadjis N, Anderson L, et al: Retroperitoneal actinomycosis masquerading as inflammatory pseudotumor. J Pediatr Surg 32: 618- 620, 1997
Raymond I, Al Salati T, Tkaczuk J, et al: CNA.42, a new monoclonal antibody directed against a fixative-resistant antigen of follicular dendritic reticulum cells. Am J Pathol 151: 1577-1585, 1997
Sciot R, Dal Cin P, Fletcher CDM, et al: Inflammatory myofibroblastic tumor of the bone. Report of two cases with evidence of clonal chromosomal changes. Am J Surg Pathol 21: 1166-1172, 1999
Selves J, Meggetto F, Brousset P, et al: Inflammatory pseudotumor of the liver. Evidence for follicular dendritic reticulum cell proliferation associated with clonal Epstein-Barr virus. Am J Surg Pathol 20: 747- 753, 1996
Shek TWH, Ho FCS, Ng IOL, et al: Follicular dendritic reticulum cell tumor of the liver. Evidence of an Epstein-Barr virus-related clonal prliferation of follicular dendritic cells. Am J Surg Pathol 20: 313- 324, 1996
Snyder CS, Dell’Agulia M, Haghighi P, et al: Clonal changes in inflammatory pseudotumor of the lung. A case report. Cancer 76: 1545-1549, 1995
Su L, Sheldon S, Weiss SW: Inflammatory myofibroblastic tumor. Cytogenetic evidence supporting clonal origin. Mod Pathol 8: 12A,1995
Tornocky T, Kelenyi G, Pajor L: EBER oligonucleotide RNA in situ hybridisation in EBV associated neoplasms. Path Oncol Res 3: 201- 205,1998
Trainor KJ, Brisco, MJ, Wan JH, et al: Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction. Blood 78: 192-196, 1991
Vaideeswar P, Madiwale CV, Desai AP, et al: Inflammatory pseudotumor of the lymph node in an HIV-positive individual. Histopathology 36: 374-375, 2000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2004
VL 10
IS 1
BP 57
EP 60
PG 4
ER
PT J
AU Kopper, L
Hajdu, M
AF Kopper, Laszlo
Hajdu, Melinda
TI Tumor Stem Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE stem cell; tumor
ID stem cell; tumor
AB Stem cells possess two basic characteristics: they are able to renew themselves and to develop into different cell types. The link between normal stem cells and tumor cells could be examined in three aspects: what are the differences and similarities in the control of self-renewal capacity between stem cells and tumor cells; whether tumor cells arise from stem cells; do tumorous stem cells exist? Since tumor cells also exhibit self-renewal capacity, it seems plausible that their regulation is similar to that of the stem cells. The infinite self-renewal ability (immortalization) is assured by several, so far only partly known, mechanisms. One of these is telomerase activity, another important regulatory step for survival is the inhibition of apoptosis. Other signal transduction pathways in stem cell regulation may also play certain roles in carcinogenesis: e.g. Notch, Sonic hedgehog (SHH), and Wnt signals. Existence of tumor stem cells was suggested since it is simpler to retain the self-renewal capacity than to reactivate the immortality program in an already differentiated cell. Moreover, stem cells live much longer than the differentiated ones, and so they are exposed for a long period of time to impairments, collecting gene errors leading to the breakdown of the regulation. However, it is still an open question whether all cells in the tumor possess the capacity that produces this tissue or not, that is: are there tumor stem cells or there are not. If tumor stem cells exist, they would be the main target for therapy: only these must be killed since the other tumor cells possess limited proliferative capacity, therefore limited life span. The only problem is that during tumor progression stem-like cells can develop continuously and the identification but mainly the prevention of their formation is still a great challenge.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Hajdu, Melinda] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular PathologyBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Thomson JA, Ilskovitz-Eldor M, Shapiro SS, et al: Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147, 1998
Lagasse E, Connors H, Al-Dhalimy M, et al: Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6: 1229-1234, 2000
Ferrari G, Cusella-De Angelis G, Coletta M, et al: Muscle regeneration by bone marrow-derived myogenic progenitor. Science 279: 1528-1530, 1998
Alison MR, Poulsom R, Jeffery R, et al: Hepatocytes from nonhepatic adult stem cells. Nature 406: 257, 2000
Eglitis MA, Mezey E: Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94: 4080-4085, 1997
Orlic D, Kajsturo J, Chimenti S, et al: Bone marrow cells regenerate infarcted myocardium. Nature 410: 701-704, 2001
Poulsom R, Forbes SJ, Hodivala-Dilke K, et al: Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 195: 229-235, 2001
Preston SL, Alison MR, Forbes SJ, et al: The new stem cell biology: something for everyone. J Clin Pathol: Mol Pathol 56: 86-96, 2003
Trosko JE, Chang CC: Stem cell theory of carcinogenesis. Toxicol Lett 49: 283, 1989
Domen J, Gandy KL, Weissmann IL: Systemic overexpression of BCL2 in the hematopoetic system protects transgenic mice from the consequences of lethal irradiation. Blood 91: 2272- 2282, 1998
Domen J, Weissman IL: Hematopoietic stem cellss need two signals to prevent apoptosis; BCL-2 can provide one of these, Kit/c-Kit signaling the other. J Exp Med 192: 1707-1718, 2000
Reya T, Morrison RJ, Clarke MF, Weissman IL:Stem cells, cancer, and cancer stem cells. Nature 414: 105-111, 2001
Taipale J, Beachy PA: The Hedgehog and Wnt signaling pathways in cancer. Nature 411: 349-354, 2001
Varnum-Finney B, et al: Pluripotent, cytokine-dependent, hematopoetic stem cells are immortalized by constitutive Notch signaling. Nat Med 6: 1278-1281, 2000
Karanu FN, et al: The Notch ligand Jagged-1 represents a novel growth factor of human hematopoetic stem cells. J Exp Med 192: 1365-1372, 2000
Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche. Nature 414: 98-104, 2001
Dick JE. Self-renewal writ in blood. Nature, 423: 231, 2003
Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423: 255- 260, 2003
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Kojika S, Griffin JD: Notch receptors and hematopoiesis. Exp Hematol 29: 1041, 2001
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Hitoshi S, Alexson T, Tropepe V, Donoviel D et al. Notch pathway molecules are essential for the maintenance, but no the generation, of mammalian neural stem cells. Genes Dev 16: 846, 2002
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Bhardwaj G, Murdoch B, Wu D, Baker DP, et al: Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol 2: 172, 2001
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Miyamoto T, Weissman IL, Akashi K: AML1/ETO expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 97: 7521-7526, 2000
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Dick JE. Breast cancer stem cells revealed. Proc Natl Acad Sci USA 100: 3547-3549, 2003
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 69
EP 73
PG 5
ER
PT J
AU Jin, R
Huang, J
Tan, PH
Bay, BH
AF Jin, Rongxian
Huang, Jingxiang
Tan, Puay-Hoon
Bay, Boon-Huat
TI Clinicopathological Significance of Metallothioneins in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE MT isoforms; biochemistry; biomarker; prognosis; chemoresistance; carcinogenesis
ID MT isoforms; biochemistry; biomarker; prognosis; chemoresistance; carcinogenesis
AB Metallothioneins (MTs) are a family of metal binding proteins that play an important role in maintaining transition metal ion homoeostasis, redox balance in the cell and fundamental cellular processes such as proliferation and apoptosis. In humans, there are 4 groups of MT proteins which are encoded by 10 functional MT isoforms. In breast tissues, MT is primarily expressed in myoepithelial and malignant epithelial cells. Immunohistochemical studies have revealed that 26% to 100% of invasive ductal breast cancers express the MT protein. The MT-1F and MT-2A isoforms have been reported to be associated with higher histological grade in breast cancer, whereas higher MT-1E mRNA expression was found in estrogen receptor-negative tumors compared to their estrogen receptor-positive counterparts. A number of studies have shown that MT expression in breast cancer is associated with poorer prognosis. In addition, metallothionein expression may have a potential role in protecting the breast cancer cell from chemotherapeutic threats to survival.
C1 [Jin, Rongxian] National University of Singapore, Department of Anatomy, 4 Medical Drive, Block MD10, S 117 597 Singapore, Singapore.
[Huang, Jingxiang] National University of Singapore, Department of Anatomy, 4 Medical Drive, Block MD10, S 117 597 Singapore, Singapore.
[Tan, Puay-Hoon] National University Hospital, Department of PathologySingapore, Singapore.
[Bay, Boon-Huat] National University of Singapore, Department of Anatomy, 4 Medical Drive, Block MD10, S 117 597 Singapore, Singapore.
RP Bay, BH (reprint author), National University of Singapore, Department of Anatomy, S 117 597 Singapore, Singapore.
EM antbaybh@nus.edu.sg
CR Kojima Y, Binz P-A, Kagi JHR: Nomenclature of metallothionein: proposal for a revision. In: Klaassen, C.D. eds. Metallothionein IV, Birkhauser Verlag, Basel, Switzerland. pp 3-6, 1999.
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Shimoda R, Achanzar WE, Qu W, et al.:Metallothionein is a potential negative regulator of apoptosis. Toxicol Sci 73: 294-300, 2003.
Cherian MG, Jayasurya A, Bay BH: Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res 533: 201-209, 2003.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 74
EP 79
PG 6
ER
PT J
AU Helal, EATh
Khalf Alla, EA
Laban, AM
Fahmy, MR
AF Helal, El-A Thanaa
Khalf Alla, E Ali
Laban, A Mohamed
Fahmy, M Remon
TI Immunophenotyping of Tumor-Infiltrating Mononuclear Cells in Ovarian Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; benign ovarian tumors; CD8+ cells; CD68+ cells
ID Ovarian cancer; benign ovarian tumors; CD8+ cells; CD68+ cells
AB Infiltrating mononuclear cells play an important role in many types of cancer. The aim of this work was to determine the immunologic characteristics of mononuclear cellular infiltrate in ovarian cancer as compared to benign ovarian tumors. Paraffin-embedded tissues obtained from 52 ovarian carcinomas and 21 benign ovarian neoplasms were examined immunohistochemically to demonstrate suppressor/cytotoxic T cells and macrophages by using CD8 and CD68 monoclonal antibodies, respectively. The mean percentage of CD8+ cells was much higher in the malignant than in the benign group (P=0.00009). Similarly, the mean level of CD68+ cells was significantly higher in carcinomas than in benign cases (P=0.006). There was a significant negative correlation between the percentage of CD8+ cells and CD68+ cells in the malignant group (P=0.000002). Conversely, no correlation could be obtained between the values of these two cell types in the benign lesions. In the malignant group, although the percentages of CD8+ cells and CD68+ cells were not related to tumor differentiation, they were significantly related to tumor type. CD8+ cells were significantly higher in the serous (P=0.02), and CD68+ cells were higher in the mucinous carcinomas (P=0.0005). CD8+ T cells and macrophages constitute a major component of the infiltrating mononuclear cells in ovarian carcinoma. Their frequency seems to be related to the tumor type rather than the degree of tumor differentiation.
C1 [Helal, El-A Thanaa] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
[Khalf Alla, E Ali] Ain Shams Faculty of Medicine, Department of Obstetrics and GynecologyCairo, Egypt.
[Laban, A Mohamed] Ain Shams Faculty of Medicine, Department of Obstetrics and GynecologyCairo, Egypt.
[Fahmy, M Remon] Ain Shams Faculty of Medicine, Department of Obstetrics and GynecologyCairo, Egypt.
RP Helal, EATh (reprint author), Ain Shams Faculty of Medicine, Department of Pathology, Cairo, Egypt.
EM thanaahelal@hotmail.com
CR Dietl J, Horny HP, Ruck P, et al: Dysgerminoma of the ovary. An immunohistochemical study of tumor-infiltrating lymphoreticular cells and tumor cells. Cancer 71:2562-2568, 1997.
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Freedman RS and Platsoucas CD: Immunotherapy for peritoneal ovarian carcinoma metastasis using ex vivo expanded tumor infiltrating lymphocytes. Cancer Treat Res 82:115- 146, 1996.
Negus R, Stamp GW, Hadley J, et al: Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 150:1723-1732, 1997.
Bonta IL and Ben-Efraim S: Involvement of inflammatory mediators in macrophage antitumor activity. J Leukoc Biol 54:613-626, 1993.
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Zusman I, Gurevich P, Gurevich E, Ben-Hur H: The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors, a review). Int J Oncol 18: 965-972, 2001.
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Puccetti L, Manetti R, Parronchi P, et al: Role of low nuclear grading of renal carcinoma cells in the functional profile of tumor-infiltrating T cells. Int J Cancer 98: 674-681, 2002.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 80
EP 84
PG 5
ER
PT J
AU Moldvay, J
Jackel, M
Bogos, K
Soltesz, I
Agocs, L
Kovacs, G
Schaff, Zs
AF Moldvay, Judit
Jackel, Marta
Bogos, Krisztina
Soltesz, Ibolya
Agocs, Laszlo
Kovacs, Gabor
Schaff, Zsuzsa
TI The Role of TTF-1 in Differentiating Primary and Metastatic Lung Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TTF-1; immunohistochemistry; lung adenocarcinoma; metastasis
ID TTF-1; immunohistochemistry; lung adenocarcinoma; metastasis
AB Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.
C1 [Moldvay, Judit] County Hospital of Pulmonology, Munkacsy M. u. 70., 2045 Torokbalint, Hungary.
[Jackel, Marta] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Soltesz, Ibolya] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Agocs, Laszlo] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Kovacs, Gabor] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Moldvay, J (reprint author), County Hospital of Pulmonology, 2045 Torokbalint, Hungary.
EM drmoldvay@hotmail.com
CR Abutaily AS, Addis BJ, Roche WR: Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 55: 662-668, 2002.
Afify AM, al-Khafaji BM: Diagnostic utility of thyroid transcription factor-1 expression in adenocarcinomas presenting in serous fluids. Acta Cytol 46: 675-678, 2002.
Bejarano PA, Mousavi F: Incidence and significance of cytoplasmic thyroid transcription factor-1 immunoreactivity. Arch Pathol Lab Med 127: 193-195, 2003.
Cai YC, Banner B, Glickman J, et al: Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol 32: 1087-1093, 2001.
Castro CY, Moran CA, Flieder DG, et al: Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases. Histopathology 39: 397-401, 2001.
Chhieng DC, Cangiarella JF, Zakowski MF, et al: Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens. Cancer 93: 330-336, 2001.
Fujita J, Ohtsuki Y, Bandoh Set al: Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines. Lung Cancer 39: 31-36, 2003.
Goldstein NS, Thomas M: Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies. Am J Clin Pathol 116: 319-325, 2001.
Gomez-Fernandez C, Jorda M, Delgado PI, et al: Thyroid transcription factor 1: a marker for lung adenoarinoma in body cavity fluids. Cancer 96: 289-293, 2002.
Haque AK, Syed S, Lele SM, et al: Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival. Appl Immunohistochem Mol Morphol 10: 103-109, 2002.
Hecht JL, Pinkus JL, Weinstein LJ, et al: The value of thyroid transcription factor-1 in cytologic preparations as a marker for metastatic adenocarcinoma of lung origin. Am J Clin Pathol 116: 483-488, 2001.
Jang KY, Kang MJ, Lee DG, et al: Utility of thyroid transcription factor-1 and cytokeratin 7 and 20 immunostaining in the identification of origin in malignant effusions. Anal Quant Cytol Histol 23: 400-404, 2001.
Lau SK, Desrochers MJ, Luthringer DJ: Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases. Mod Pathol 15: 538-542, 2002.
Lau SK, Luthringer DJ, Eisen RN: Thyroid transcription factor- 1: a review. Appl Immunohistochem Mol Morphol 10: 97- 102, 2002.
Merchant SH, Amin MB, Tamboli P, et al: Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas. Am J Surg Pathol 25: 1515-1519, 2001.
Nakamura N, Miyagi E, Murata S, et al: Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod Pathol 15: 1058-1067, 2002.
Ng WK, Chow JC, Ng PK: Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens. Cancer 96: 43-48, 2002.
Ordonez NG: Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 24: 1207-1223, 2000.
Srodon M, Westra WH: Immunohistochemical staining for thyroid transcription factor-1: a helpful aid in discerning primary site of tumor origin in patients with brain metastases. Hum Pathol 33: 642-645, 2002.
Sturm N, Lantuejoul S, Laverriere MH, et al: E. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14, 34betaE12, expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Hum Pathol 32: 918-925, 2001.
Wu M, Wang B, Gil J, et al: p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol 119: 696-702, 2003.
Yatabe Y, Mitsudomi T, Takahashi T: TTF-1 expression in pulmonary adenocarcinomas. Am J Surg Pathol 26: 767-773, 2002.
Zamecnik J, Kodet R: Value of thyroid transcription factor-1 and surfactant apoprotein A in the differential diagnosis of pulmonary carcinomas: a study of 109 cases. Virchows Arch 440: 353-361, 2002.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 85
EP 88
PG 4
ER
PT J
AU Kacar Ozkara, S
Corakci, A
AF Kacar Ozkara, Sevgiye
Corakci, Aydin
TI Significantly Decreased P27 Expression In Endometrial Carcinoma Compared to Complex Hyperplasia with Atypia (correlation with p53 expression)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrium; carcinoma; hyperplasia; p27; p53
ID Endometrium; carcinoma; hyperplasia; p27; p53
AB P27 expression was examined on paraffin-embedded specimens in proliferative, secretory, hyperplastic and neoplastic human endometrium by immunohistochemistry. The results of p27 immunoreactivity in endometrial carcinomas were compared with clinicopathological indicators as well as with p53 expression. Thirty-eight cases of endometrial carcinoma, 30 normal functional (15 proliferative, 15 secretory), 24 hyperplastic endometrium (12 without atypia, 12 with atypia) specimens were studied by using monoclonal p27 and p53 antibodies. The streptavidin-biotin-peroxidase detection system was used and the intensity and the distribution of immunoreactivity was evaluated semiquantitatively. p27 expression was present both in the proliferative and secretory phases; the expression being stronger in the secretory period. In complex hyperplasia with atypia, p27 expression was even higher and it was significantly reduced in the endometrial carcinoma group (p<0.05). No significant correlation was found between p27 expression and any of the clinicopathologic prognostic parameters (p>0.05). Nuclear p53 expression was detected in 13 (34.2%) patients with endometrial carcinoma and was higher in non-endometrioid carcinomas and in tumors with increasing FIGO grade (p<0.05). High expression of p53 was not found to be a significant prognostic indicator of survival (p>0.05). No p53 expression was detected in the endometria with proliferation, secretion or hyperplasia either simple without atypia or complex with atypia. Surprisingly, tumors with absent/low p27 expression showed absent/low p53 expression. Our data suggest that p27 is necessary to control the proliferation of endometrium and its loss of expression seems to play a role in some aspects of endometrial carcinogenesis.
C1 [Kacar Ozkara, Sevgiye] Kocaeli University School of Medicine, Department of Pathology, Mustafa Pasa Mah, Bagdat Cad. 0712. Sok. No. 19/6, 41400 Kocaeli, Gebze, Turkey.
[Corakci, Aydin] Kocaeli University School of Medicine, Department of Gynecology and ObstetricsKocaeli, Turkey.
RP Kacar Ozkara, S (reprint author), Kocaeli University School of Medicine, Department of Pathology, 41400 Kocaeli, Turkey.
EM emrecan1999@yahoo.com
CR Al Kushi A, Lim P, Aquino-Parsons C, et al: Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium. Mod Pathol 15: 365-371, 2002
Bamberger AM, Riethdorf L, Milde-Langosch K, et al: Strongly reduced expression of the cell cycle inhibitor p27 in endometrial neoplasia. Virchows Arch 434: 423-428, 1999
Berchuck A, Kohler MF, Marks JR, et al: The p53 tumor suppressor gene frequently is altered in gynecologic cancers. Am J Obstet Gynecol 170: 246-252, 1994
Cinel L, Polat A, Aydin O, et al: Bcl-2, iNOS, p53 and PCNA expression in normal, disordered proliferative, hyperplastic and malignant endometrium. Pathology International 52: 384-389, 2002
Dubowy RL, Feinberg RF, Keefe DL, et al: Improved endometrial assessment using cyclin E and p27. Fertil Steril 80: 146- 156, 2003
Elhafey AS, Papadimitriou JC, El-hakim MS, et al: Computerized image analysis of p53 and proliferating cell nuclear antigen expression in benign, hyperplastic and malignant endometrium. Arch Pathol Lab Med 125: 872-879, 2001
Enomoto T, Fujita M, Inoue M, et al: Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium. Cancer Research 53: 1883-1888, 1993
Erdem O, Erdem M, Dursun A, et al: Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: comparison with traditional clinicopathologic variables. Int J Gynecol Pathol 22: 254-260, 2003
Kaku T, Kamura T, Hirakawa T, et al: Endometrial carcinoma associated with hyperplasia - Immunohistochemical study of angiogenesis and p53 expression. Gynecol Oncol 72: 51-5, 1999
Kato N, Watanabe J, Jobo T, et al: Immunohistochemical expression of cyclin E in endometrial adenocarcinoma, endometrioid type, and its clinicopathological significance. J Cancer Res Clin Oncol 129: 222-226, 2003 [Epub 2003 Apr 08]
Kimura F, Watanabe J, Hata H, et al: PTEN immunohistochemical expression is suppressed in G1 endometrioid adenocarcinoma of the uterine corpus. J Cancer Res Clin Oncol [Epub ahead of print] , 2003 Dec 20
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Masciullo V, Susini T, Zamparelli A, et al: Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1, in estrogen-related endometrial adenocarcinomas. Clin Cancer Res 9: 5332-5338, 2003
Miturski R, Semczuk A, Tomaszewski J, et al: Bcl-2 protein expression in endometrial carcinoma: the lack of correlation with p53. Cancer Letters 133: 63-69, 1998
Oshita T, Shigemasa K, Nagai N, et al: p27, cyclin E, and CDK2 expression in normal and cancerous endometrium. Int J Oncol 21: 737-743, 2002
Saegusa M, Machida D, Okayasu I: Age-dependent differences in tumor cell polarity in endometrial carcinomas. J Cancer Res Clin Oncol 128: 205-213, 2002
Shiozawa T, Horiuchi A, Kato K, et al: Up-regulation of p27Kip1 by progestins is involved in the growth suppression of the normal and malignant human endometrial glandular cells. Endocrinology 142: 4182-4188, 2000
Shiozawa T, Nikaido T, Nakayama K, et al: Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone. Mol Hum Reprod 4: 899-905, 1998
Siufi AA, Cotrim G, Da Silva ID, et al: Effects of tamoxifen therapy on the expression of p27 protein in the endometrium of women with primary breast cancer. Int J Oncol 23: 1545-1551, 2003
Suzuki C, Matsumoto T, Sonoue H, et al: Prognostic significance of the infiltrative pattern invasion in endometrioid adenocarcinoma of the endometrium. Pathol Int 53: 495-500, 2003
Watanabe J, Sato H, Kanai T, et al: Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus – correlation with proliferation and clinicopathological parameters. Br J Cancer 87: 81-85, 2002
Zhuang YH, Sarca D, Weisz A, et al: Cell type-specific induction of cyclin D and cyclin-dependent kinase inhibitor p27(kip1, expression by estrogen in rat endometrium. J Steroid Biochem Mol Biol 78: 193-199, 2001
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 89
EP 97
PG 9
ER
PT J
AU Szende, B
Farid, P
Vegso, Gy
Perner, F
Kopper, L
AF Szende, Bela
Farid, Parvaneh
Vegso, Gyula
Perner, Ferenc
Kopper, Laszlo
TI Apoptosis and P53, Bcl-2 and Bax Gene Expression in Parathyroid Glands of Patients with Hyperparathyroidism
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Parathyroid; adenoma; hyperplasia; carcinoma; mitosis; apoptosis; Bcl-2; p53; Bax
ID Parathyroid; adenoma; hyperplasia; carcinoma; mitosis; apoptosis; Bcl-2; p53; Bax
AB Altogether 107 patients were operated on at the Department of Transplantation and Surgery of Semmelweis University in the past four years, for clinical symptoms of hyperparathyroidism. Clinical and laboratory data of the patients supported the diagnosis of primary or secondary hyperparathyroidism. Chronically impaired renal function was found in 52 cases. The removed parathyroid glands showed hyperplasia in 54, adenoma in 50 and carcinoma in 3 cases. The majority of parathyroid lesions in primary hyperparathyroidism were adenomas (41 cases) and in secondary hyperparathyroidism were hyperplasias (43 cases). The ratio of oxyphil to chief cells as well as occasional mitotic and apoptotic figures were determined. The oxyphil component was present in both hyperplastic and tumorous lesions. Apoptosis and mitosis were rarely seen in hyperplasias and adenomas (under 2%), whereas in carcinomas 3% of the tumor cells were apoptotic and 4% showed mitosis. Cytoplasmic p53 positivity could be observed in 3 of the adenomas and in 2 of the hyperplasias. The carcinomas, four adenomas and 3 hyperplasias showed nuclear p53 positivity. Bcl-2 and Bax were detected in the cytoplasm of the tumor cells in the majority of adenomas and in the cells of hyperplasias. Oxyphil cells were more frequently positive than chief cells or clear cells. Colocalization of Bcl-2 and Bax was found randomly in all types of lesions. The very low incidence of carcinoma, the low mitotic and apoptotic ratio in adenomas and hyperplasias suggest a potent antiproliferative defense mechanism in the parathyroid cell population. This may also be reflected in the cytoplasmic colocalization of various gene products which regulate cell death and cell proliferation. No significant differences in the p53, Bcl-2 and Bax spectrum were found between the primary and secondary (i.e. renal failure) parathyroid alterations.
C1 [Szende, Bela] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi u. 26, H-1085 Budapest, Hungary.
[Farid, Parvaneh] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi u. 26, H-1085 Budapest, Hungary.
[Vegso, Gyula] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Kopper, Laszlo] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi u. 26, H-1085 Budapest, Hungary.
RP Szende, B (reprint author), Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, H-1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Roth SJ: The parathyroid gland. In Silverberg, S G.Principals and practice of surgical pathology. Second edition. Churchill Livingstone, New York, pp; 1923-1955, 1990
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Ricci F, Mingazzini PL, Sebastiani V, et al: P53 as a marker of differentiation between hyperplastic and adenomatous lesions of parathyroids. Int Diag Pathol 6:229-235, 2002
Stojadinovic A, Hoos A, Nissan A, et al: Cordon-Cardo C, Shaha AR, Brennan MF, Singh B, Gossein RA. Parathyroid neoplasms: Clinical, histopathological, and tissue microarraybased molecular analysis.Hum Pathol 34: 54-64, 2003
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 98
EP 103
PG 6
ER
PT J
AU Ghosh, S
Maity, P
AF Ghosh, Sonali
Maity, Putul
TI Isolation and Purification of Vascular Endothelial Growth Factor (VEGF) from Ascitic Fluid of Ovarian Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VEGF; ascitic fluid; ovarian cancer
ID VEGF; ascitic fluid; ovarian cancer
AB Vascular Endothelial Growth Factor (VEGF) or Vascular Permeability Factor (VPF) is an angiogenic cytokine expressed by many human and animal tumors. Because of the importance of VEGF in animal tumors, we purified VEGF/VPF from ascitic fluid of ovarian cancer patients with heparin sepharose column. The purified protein gave protein bands of 37 and 26 kD, respectively in 12% SDS PAGE. The specificity of the purified protein was determined with dot blot, trans-immunoblot and ELISA using polyclonal goat anti-VEGF antibody (Santa Cruz Biotechnology). The vasodilatatory effect of the purified protein was confirmed by a vascular permeability assay on mouse. A polyclonal mouse antibody was raised against the purified protein, which recognized the same protein by ELISA, transimmunoblot and dot-blot analysis. It has been also found that the raised polyclonal antibody in mouse- and the commercial VEGF polyclonal antibody (Santa Cruz Biotechnology) both inhibited in vitrocell proliferation of human MCF-7 cell line. This study shows for the first time an effort to purify VEGF from human source.
C1 [Ghosh, Sonali] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 700026 Kolkata, India.
[Maity, Putul] Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 37, S. P. Mukherjee Road, 700026 Kolkata, India.
RP Maity, P (reprint author), Chittaranjan National Cancer Institute, Department of Metabolic Regulation, 700026 Kolkata, India.
EM putulmaity@yahoo.co.in
CR Beliveau R, Gingras D, Kruger E A, et al: The antiangiogenic agent Neovastat, AE-941, inhibits vascular endothelial growth factor mediated biological effects. Clin Cancer Res 8: 1242- 1250, 2002.
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Yabushita H, Shimazu M, Noguchi M, et al.: Vascular endothelial growth factor activating matrix metalloproteinase in ascitic fluid during peritoneal dissemination of ovarian cancer. Oncol Rep10: 89-95, 2003.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 104
EP 108
PG 5
ER
PT J
AU Csiszar, A
Szentes, T
Haraszti, B
Balazs, A
Petranyi, GGy
Pocsik,
AF Csiszar, Anna
Szentes, Tamas
Haraszti, Bea
Balazs, Annamaria
Petranyi, G Gyozo
Pocsik, Eva
TI The Pattern of Cytokine Gene Expression in Human Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cytokine; gene expression; colorectal carcinoma; RT-PCR
ID cytokine; gene expression; colorectal carcinoma; RT-PCR
AB Systemic and local cytokine environment may modulate the immunogenicity of colorectal cancer cells, and affect anti-tumor immune functions of tumorinfiltrating lymphocytes. We therefore investigated cytokine mRNA expression patterns in tumors and peripheral blood mononuclear cells (PBMC) from patients with colorectal adenocarcinoma. IL-2, IFN-g, tumor necrosis factor-a (TNF-a), IL-4, IL-6, IL-8, IL-10 and IL-1b mRNAs in single cell suspension of freshly isolated colorectal cancer tissue were studied by RT-PCR. Frequencies of cytokine gene expression were compared to those in normal colonic mucosa from tumor patients. The frequencies of IL-2, IFN-g, IL-4 and IL-10 gene expression were also determined in peripheral blood mononuclear cells from patients with colorectal adenocarcinoma and compared to those of healthy individuals. Tumor samples were more frequently positive for IFN-g, IL-2, TNF-a and IL-10 gene expression than normal mucosa (p=0.0001, p=0.0118, p=0.001 and p<0.0001, respectively). Frequencies of IL-2 and TNF-a gene expressions were significantly higher in tumors with a diameter <5 cm, than in those with a diameter >5 cm. The genes for IL-6, IL-1b and IL-8 were commonly expressed in both tumor tissue and normal colonic mucosa. IFN-g transcripts were detected in more PBMC samples from patients with colorectal cancer than those from normal controls (p=0.0449). Thus, colorectal cancer tissue is characterized by a specific pattern of cytokine gene expression. It is likely that multiple interactions between pro- and anti-inflammatory cytokines regulate tumor growth and the functional activity of tumor-infiltrating lymphocytes.
C1 [Csiszar, Anna] New York Medical College, Department of PhysiologyValhalla, USA.
[Szentes, Tamas] Szent Imre Hospital, Department of SurgeryBudapest, Hungary.
[Haraszti, Bea] National Medical Center, Department of Hematology and Stem Cell Transplantation, 64 Dioszegi ut, H-1113 Budapest, Hungary.
[Balazs, Annamaria] New York Medical College, Department of PhysiologyValhalla, USA.
[Petranyi, G Gyozo] National Medical Center, Department of Hematology and Stem Cell Transplantation, 64 Dioszegi ut, H-1113 Budapest, Hungary.
[Pocsik, Eva] National Medical Center, Department of Hematology and Stem Cell Transplantation, 64 Dioszegi ut, H-1113 Budapest, Hungary.
RP Pocsik, (reprint author), National Medical Center, Department of Hematology and Stem Cell Transplantation, H-1113 Budapest, Hungary.
EM pocsik@ohvi.hu
CR Hilgenfeld RU and Kreuser ED: Immunological and biochemical modulation in the treatment of advanced colorectal cancer: Update and future directions. Curr Topics Microbiol Immunol 213: 217-240, 1996.
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Shibata M, Nezu T, Takekawa M et al: Serum levels of interleukin- 10 and interleukin-12 in patients with colorectal cancer. Ann N Y Acad Sci 795: 410-412,1996.
Tsushima H, Kawata S, Tamura S et al: High levels of transforming growth factor 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 110: 375-382, 1996.
Zaloudik J, Lauerova L, Janakova L et al: Significance of pretreatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver. Hepatogastroenterology 46: 220-227, 1999.
Heriot AG, Marriott JB, Cookson S et al: Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection. Br J Cancer 82: 1009- 1012, 2000.
Lahm H, Schindel M, Frikart L et al: Selective suppression of cytokine secretion in whole blood cell cultures of patients with colorectal cancer. Br J Cancer 78: 1018-1023, 1998.
O’Hara RJ, Greenman J, Drew PJ et al: Impaired interleukin- 12 production is associated with a defective anti-tumor response in colorectal cancer. Dis Colon Rectum 41: 460-463, 1998.
Brew R, Southern SA, Flanagan BF et al: Detection of interleukin- 8 mRNA and protein in human colorectal carcinoma cells. Eur J Cancer 32A: 2142-2147, 1996.
Gastl GA, Abrams JS, Nanus DM et al: Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin- 6 expression. Int J Cancer 55: 96-101, 1993.
Langerak AD, Garewal HS: Transforming growth factor-b1: a useful tumor marker in patients with colorectal carcinoma? Cancer 85: 517-519, 1999.
Mauerer MJ, Walter W, Martin D et al: Interleukin-7, IL-7, in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes. Scand J Immunol 45: 182-192, 1997.
Coca S, Perez-Piqueras J, Martinez D et al: The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79: 2320-2328, 1997.
Di Giorgio A, Botti C, Tocchi A et al: The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients. Int Surg 77: 256-260, 1992.
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Mosmann TR, Li L, Sad S: Function of CD8 T-cell subsets secreting different cytokine patterns. Semin Immunol 9: 87-92, 1997.
Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev 12: 375-391, 2001.
Rosen EM, Zitnik R J, Elias JA et al: The interaction of HGFSF with other cytokines in tumor invasion and angiogenesis. EXS 65: 301-310, 1993.
Opdenakker G, Van den Steen PE, Dubois B et al: Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69: 851-859, 2001.
Kossakowska AE, Urbanski SJ, Janowska-Wieczorek A: Matrix metalloproteinases and their tissue inhibitors - expression, role and regulation in human malignant non-Hodgkin’s lymphomas. Leuk Lymphoma 39: 485-493, 2000.
Wilson J, Balkwill F: The role of cytokines in the epithelial cancer microenvironment. Semin Cancer Biol 12: 113-120, 2002.
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Luo J S, Kammerer R, von Kleist S: Comparison of the effects of immunosuppressive factors from newly established colon carcinoma cell cultures on human lymphocyte proliferation and cytokine secretion. Tumour Biol 21: 11-20, 2000.
Csiszar A, Szentes T, Haraszti B et al: Characterization of cytokine mRNA expression in tumour-infiltrating mononuclear cells and tumour cells isolated freshly from human colorectal carcinomas. Eur Cyt Netw 12: 87-96, 2001.
Csiszar A, Nagy G, Gergely P, Pozsonyi T, Pocsik E: Increased interferon-, IFN-g), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells, PBMC, from patients with systemic lupus erythematosus, SLE). Clin Exp Immunol 122: 464-470, 2000.
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Zou W, Durand-Gasselin I, Dulioust A et al: Quantification of cytokine gene expression by competitive PCR using a colorimetric assay. Eur Cyt Netw 6: 257-264, 1995.
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Piancatelli D, Romano P, Sebastiani P et al: Local expression of cytokines in human colorectal carcinoma: evidence of specific interleukin-6 gene expression. J Immunother 22: 25-32, 1999.
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Takagi K, Tomita K, Fukushima et al: Endogenous TNF inducibility and prognosis of colorectal cancer. Anticancer Res 18: 4141-4146, 1998.
Etoh T, Shibuta K, Barnard GF et al: Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. Clin Cancer Res 6: 3545-3551, 2000.
Minami S, Furui J, Kanematsu T: Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. Cancer Res 61: 2732-2735, 2001.
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Salazar-Onfray F: Interleukin-10: a cytokine used by tumors to escape immunosurveillance. Med Oncol 16: 86-94, 1999.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 109
EP 116
PG 8
ER
PT J
AU Vermes, G
Acs, N
Szabo, I
Langmar, Z
Jaray, B
Banhidy, F
AF Vermes, Gabor
Acs, Nandor
Szabo, Istvan
Langmar, Zoltan
Jaray, Balazs
Banhidy, Ferenc
TI Simultaneous Bilateral Occurrence of a Mixed Mesodermal Tumor and Cystadenocarcinoma in the Ovary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE malignant mixed mesodermal tumor; ovary; simultaneous occurrence
ID malignant mixed mesodermal tumor; ovary; simultaneous occurrence
AB The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.
C1 [Vermes, Gabor] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi u. 78/a, H-1082 Budapest, Hungary.
[Acs, Nandor] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi u. 78/a, H-1082 Budapest, Hungary.
[Szabo, Istvan] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi u. 78/a, H-1082 Budapest, Hungary.
[Langmar, Zoltan] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi u. 78/a, H-1082 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Banhidy, Ferenc] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi u. 78/a, H-1082 Budapest, Hungary.
RP Vermes, G (reprint author), Semmelweis University, 2nd Department of Obstetrics and Gynecology, H-1082 Budapest, Hungary.
CR Fowler JM, Nathan L, Nieberg RK, Berek JS. Mixed mesodermal sarcoma of the ovary in a young patient. Eur J Obstet Gynecol Reprod Biol 65:249-253, 1966
Le T, Krepart GV, Lotocki RJ, Heywood MS. Malignant mixed mesodermal ovarian tumor treatment and prognosis: A 20 – year experience. Gynecol Oncology 65:237-240, 1997
Ariad S, Rabinovitz A,Yanai-Inbar I, Piura B. Mixed uterine mesodermal sarcoma in the population of southern Israel in the years 1996-1971–clinical and pathological charasteristics. Harefuah 134:93-6, 159, 1998
Nakata Y, Morita M, Mori Y. A malignant mixed mesodermal tumor of the ovary. Gan No Rinsho 36:2210-2217, 1990
Li H, Shi S, Zhang W. Malignant mixed mesodermal tumors of the ovary: a clinical analysis of 12 cases. Zhonghua Zhong Liu Za Zhi 20:460-462,1998
Piura B, Rabinovich A, Yanai-Inbar I, et al. Primary sarcoma of the ovary: report of five cases and review of the literature. Eur J Gynecol Oncol 19:257-261,1998
Kaji Y, Sugimura K, Yamamoto N, et al: A case of malignant mixed mesodermal tumor, MMMT, of the ovary: MR features before and after chemotherapy. Radiat Med 17:81-3,1999
Krigman HR, Coogan AC, Marks JR: Simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous adenocarcinoma. Arch Pathol Lab Med 119:99-103, 1995
Ergeneli MH, Demirhan B, Duran EH, Coskun M: Malignant mixed mesodermal tumor arising in a benign cystic teratoma. Eur J Obstet Gynecol Reprod Biol 83:191-4,1999
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 117
EP 120
PG 4
ER
PT J
AU Kabukcuoglu, F
Kabukcuoglu, Y
Yilmaz, B
Erdem, Y
Evren, I
AF Kabukcuoglu, Fevziye
Kabukcuoglu, Yavuz
Yilmaz, Banu
Erdem, Yesim
Evren, Ismail
TI Mazabraud's Syndrome: Intramuscular Myxoma Associated with Fibrous Dysplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Mazabraud's syndrome; intramuscular myxoma; fibrous dysplasia
ID Mazabraud's syndrome; intramuscular myxoma; fibrous dysplasia
AB The association of fibrous dysplasia and intramuscular myxoma is a rare disease known as Mazabraud's syndrome. Both lesions tend to occur in the same anatomical region. The relationship between fibrous dysplasia and myxoma remains unclear, where an underlying localized error in tissue metabolism has been proposed to explain this occasional coexistence. Another example of this syndrome in a 52 year-old woman is reported. The patient presented with a soft tissue mass at the anteromedial mid part of the left thigh. After excision of the mass, three separate bone lesions were detected in her control MRI. The soft tissue mass was misdiagnosed as liposarcoma in another center, and the bone lesions were interpreted as metastasis. The hypocellularity and the indistinct vascular pattern of the lesion were consistent with myxoma. The Jam-Shidi needle biopsies of the osseous lesions were diagnosed as fibrous dysplasia. The recognition of this entity is important for appropriate management of the patient. Patients with soft tissue myxomas should be thoroughly examined for fibrous dysplasia. The greater risk of sarcomatous transformation in fibrous dysplasia with Mazabraud's syndrome should also be kept in mind.
C1 [Kabukcuoglu, Fevziye] Sisli Etfal Training and Research Hospital, Department of Pathology, No:10/1 Dogancilar, Uskudar, 81160 Istanbul, Turkey.
[Kabukcuoglu, Yavuz] Sisli Etfal Training and Research Hospital, Department of Orthopedics and TraumatologyIstanbul, Turkey.
[Yilmaz, Banu] Sisli Etfal Training and Research Hospital, Department of Pathology, No:10/1 Dogancilar, Uskudar, 81160 Istanbul, Turkey.
[Erdem, Yesim] Sisli Etfal Training and Research Hospital, Department of Pathology, No:10/1 Dogancilar, Uskudar, 81160 Istanbul, Turkey.
[Evren, Ismail] Sisli Etfal Training and Research Hospital, Department of Pathology, No:10/1 Dogancilar, Uskudar, 81160 Istanbul, Turkey.
RP Kabukcuoglu, F (reprint author), Sisli Etfal Training and Research Hospital, Department of Pathology, 81160 Istanbul, Turkey.
EM ykabukcuoglu@yahoo.com
CR Blasier DR, Ryan JR, Schaldenbrand MF: Multiple myxomata of soft tissue associated with polyostotic fibrous dysplasia: A case report. Clin Orthop 206: 211-214, 1986
Cabral CE, Guedes P, Fonseca T, et al: Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud’s syndrome. Skeletal Radiol. 27: 278-282, 1998
Cohen MM, Siegal GP: Congenital and inherited syndromes. In: Pathology and Genetics of Tumours of Soft Tissue and Bone, Eds: Fletcher CDM, Unni KK, Mertens F, WHO Classification of Tumours, IARC Press, Lyon, 2002, pp 357-359
Court-Payen M, Jensen LI, Bjerregaard B, et al: Intramuscular myxoma and fibrous dysplasia of bone – Mazabraud’s syndrome. Acta Radiol. 38: 368-371, 1997
Enzinger FM, Weiss SW: Benign Soft Tissue Tumors and Psedotumors of Miscellaneous Type. In: Enzinger and Weiss’s Soft Tissue Tumors., Eds: Weiss SW, Goldblum JR), Ed 4. St Louis, Mosby, 2001, pp.1419-1481
Gianoutsos MP, Thompson JF, Marsden FW: Mazabraud’s Syndrome: Intramuscular myxoma associated with fibrous dysplasia of bone. Aust N Z J Surg 60: 825-828, 1990
Iwasko N, Steinbach LS, Disler D, et al: Imaging findings in Mazabraud’s syndrome: seven new cases. Skeletal Radiol. 31:81-87, 2002
Jhala DN, Eltoum I, Carrol AJ, et al: Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud’s syndrome: a case report emphasizing the cytological and cytogenic findings. Hum Pathol. 34:1354-1357, 2003
Lopez-Ben R, Pitt MJ, Jaffe KA and Siegal GP: Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud’s syndrome. Skeletal Radiol. 28: 522-526, 1999
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2004
VL 10
IS 2
BP 121
EP 123
PG 3
ER
PT J
AU Bruheim, S
Bruland, SO
Breistol, K
Maelandsmo, MG
Fodstad, O
AF Bruheim, Skjalg
Bruland, S Oyvind
Breistol, Knut
Maelandsmo, M Gunhild
Fodstad, Oystein
TI Human Osteosarcoma Xenografts and Their Sensitivity to Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE osteosarcoma; human tumor xenograft; chemotherapy; drug resistance
ID osteosarcoma; human tumor xenograft; chemotherapy; drug resistance
AB Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still die due to their disease. Further improvements in the management of osteosarcoma may rely on a more individualised treatment strategy, as well as on the introduction of new drugs. To aid in the preclinical evaluation of new candidate substances against osteosarcoma, we have established 11 human osteosarcoma xenograft lines and characterised them with regard to response to five different reference drugs. Doxorubicin, cisplatin methotrexate, ifosfamide and lomustine were effective in 3/11, 3/11, 1/10, 5/11 and 4/11 of the xenografts, respectively. Five xenografts were resistant to all compounds tested. We also assessed the mRNA expression levels of the xenografts for the O6-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II- (Topo II)-a, Gluthathione-S-transferase (GST)-p, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-p and doxorubicin growth inhibition (r=-0.66; p<0.05), and between the transcript levels of MGMT and the effect of lomustine (r=-0.72; p<0.01), whereas the expression of MRP1 and cisplatin growth inhibition was positively correlated (r=0.82; p<0.005). This panel of xenografts should constitute a good tool for pharmacological and molecular studies in osteosarcoma.
C1 [Bruheim, Skjalg] The Norwegian Radium Hospital, Department of Tumor Biology, Montebello, 0310 Oslo, Norway.
[Bruland, S Oyvind] The Norwegian Radium Hospital, Department of Medical Oncology and RadiotherapyOslo, Norway.
[Breistol, Knut] The Norwegian Radium Hospital, Department of Tumor Biology, Montebello, 0310 Oslo, Norway.
[Maelandsmo, M Gunhild] The Norwegian Radium Hospital, Department of Tumor Biology, Montebello, 0310 Oslo, Norway.
[Fodstad, Oystein] The Norwegian Radium Hospital, Department of Medical Oncology and RadiotherapyOslo, Norway.
RP Bruheim, S (reprint author), The Norwegian Radium Hospital, Department of Tumor Biology, 0310 Oslo, Norway.
EM skjalg.bruheim@labmed.uio.no
CR Malawer MM, Link MP, Donaldson SS. Sarcomas of the Bone. In DeVita VT, Hellmann S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology 2001; 6th Edition, Volume 2):18911936.
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Budach W, Budach V, Stuschke M, el al: Efficacy of ifosfamide, dacarbazine, doxorubicin and cisplatin in human sarcoma xenografts. Br J Cancer 70:29-34, 1994
Meyer WH, Houghton JA, Houghton PJ, et al: Development and characterization of pediatric osteosarcoma xenografts. Cancer Res 50:2781-2785, 1990
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Scotlandi K, Serra M, Nicoletti G, et al: Multidrug resistance and malignancy in human osteosarcoma. Cancer Res 56:2434- 2439, 1996
Scotlandi K, Manara MC, Serra M, et al: The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells. Oncogene 18:739-746, 1999
Serra M, Scotlandi K, Reverter-Branchat G, et al: Value of Pglycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities. J Clin Oncol 21:536-542, 2003
Serra M, Maurici D, Scotlandi K, et al: Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma. Int J Oncol 14:301-307, 1999
Chan HS, Grogan TM, Haddad G, et al: P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. J Natl Cancer Inst 89:1706-1715, 1997
Baldini N, Scotlandi K, Barbanti-Brodano G, et al: Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 333:1380-1385, 1995
Posl M, Amling M, Grahl K, et al: P-glycoprotein expression in high grade central osteosarcoma and normal bone cells. An immunohistochemical study. Gen Diagn Pathol 142:317-325, 1997
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Gorlick R, Huvos AG, Heller G, et al: Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17:2781-2788, 1999
Suto R, Abe Y, Nakamura M, et al: Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo. Int J Oncol 12:287-291, 1998
Radig K, Hackel C, Herting J, et al: Expression of P-glycoprotein in high grade osteosarcomas with special emphasis on chondroblastic subtype. Gen Diagn Pathol 142:139-145, 1997
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Ifergan I, Meller I, Issakov J, Assaraf YG. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer 98:1958-1966, 2003
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Uozaki H, Horiuchi H, Ishida T, et al: Overexpression of resistance- related proteins, metallothioneins, glutathione-S-transferase pi, heat shock protein 27, and lung resistance-related protein, in osteosarcoma. Relationship with poor prognosis. Cancer 79:2336-2344, 1997
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Gerson SL. Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 20:2388-2399, 2002
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 133
EP 141
PG 9
ER
PT J
AU Mehes, G
Speich, N
Bollmann, M
Bollmann, R
AF Mehes, Gabor
Speich, Norbert
Bollmann, Magdolna
Bollmann, Reinhard
TI Chromosomal Aberrations Accumulate in Polyploid cells of High-grade Squamous Intraepithelial Lesions (HSIL)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HPV; aneuploidy; chromosome; cytology; cervix
ID HPV; aneuploidy; chromosome; cytology; cervix
AB Persistant infection with human papillomavirus (HPV) of the uterine cervix is related with cytological atypia (SIL), the oncogenic potential of which is unclear in a given time point of monitoring. HPVinduced genetic instability result in polyploidization as well as in low frequency random chromosome aberrations in squamous cells. In the present work we analyzed whether highly polyploid/aneuploid cells reflect genomic changes at the chromosomal level. 13 samples with the cytological diagnosis of HSIL were analyzed for HPV type and nuclear DNA content measured by laser scanning cytometry (LSC). Hyperdiploid cells with >5c and with >9c DNA content were further analyzed for numerical aberrations of the chromosomes 3 and 17 by fluorescence in situ hybridization (FISH) following repositioning. Cells with >5c DNA content were found more frequently than cells with >9c DNA content (5-98 and 1-44 cells, respectively). The FISH analysis demonstrated frequent polysomies, however, the rate of aneusomy (other than 2, 4, 8 or 16 chromosome copies) was significantly higher in cells with >9c DNA content than in cells with >5c DNA content or the normal diploid cells. The imbalance of chromosome 3 and 17 copy number was also increased in cells with >9c DNA content. Moreover, in three out of the 13 analyzed HSIL samples, recurrent abnormal chromosome 3/17 ratio was demonstrated in a significant part of the cells, indicating a common origin of these cells. Highly polyploid/aneuploid cells in HSIL accumulate cytogenetic aberrations detectable by FISH analysis. These cells may reflect early changes with tumorigenic potential in a very concentrated fashion.
C1 [Mehes, Gabor] Institute of PathologyBonn-Duisdorf, Germany.
[Speich, Norbert] University of Bonn, Institute of PathologyBonn, Germany.
[Bollmann, Magdolna] Institute of PathologyBonn-Duisdorf, Germany.
[Bollmann, Reinhard] Institute of PathologyBonn-Duisdorf, Germany.
RP Mehes, G (reprint author), Institute of Pathology, Bonn-Duisdorf, Germany.
EM mehesg@pathology.pote.hu
CR zur Hausen H: Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 184: 9-13, 1991
Ferenczy A, Franco E: Persistent human papillomavirus infection and cervical neoplasia. Lancet Oncol 3:11-167, 2002
Bosch FX, Lorincz A, Munoz N, et al: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244- 265, 2002 4 Zielinsky GD, Snijders PJF, Rozendaal L, et al. HVP presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears. Br J Cancer 85: 398-404, 2001 5. The 1988 Bethesda System for reporting cervical/vaginal cytologic diagnoses. Acta Cytol 33: 567-72, 1989 6. Solomon D, Davay D, Kurman R, et al: The Bethesda 2001 Workshop: The 2001 Bethesda System: terminology of reporting results of cervical cytology. JAMA 287: 2114-2119, 2002 7. Bocking A, Chatelain R: Diagnostic and prognostic value of DNA cytometry in gynaecologic cytology. Anal Quant Cytol Histol 11: 177-186, 1989 8. Hanselaar AG, Vooijs GP, Mayall BH, et al: DNA changes in progressive cervical intraepithelial neoplasia. Anal Cell Pathol 4: 315- 324, 1992 9. Winkler B, Crum CP, Fujii T, et al: Koilicytic lesions of the cervix: the relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA-content. Cancer 53: 1081-1087, 1984 10. Bibbo M, Dytch HE, Alenghat E, et al: DNA ploidy profiles as indicators in CIN lesions. Am J Clin Pathol 92: 261-265, 1989 11. Bollmann R, Bollmann M, Henson DE, Bodo M: DNA-cytometry confirms the utility of the Bethesda System for the classification of Papanicolaou smears. Cancer 93: 222-228, 2001 12. Bollmann R, Mehes G, Torka R, et al: HPV typing and DNA ploidy determination in squamous intraepithelial lesions, SIL, in liquid fixed cytological samples. Cancer 99: 57-62, 2003 13. Bollmann R, Mehes G, Torka R, et al: Determination of features indicating progression in ASCUS: HPV typing and DNA ploidy analysis from liquid based cytological samples. Cancer 99: 113- 117, 2003 14. Tarnok A, Gerstner AO: Clinical applications of laser scanning cytometry. Cytometry 50: 133-143, 2002 15. Hanselaar AG, Bocking A, Gundlach H, et al: International Consensus Conference on the Fight Against Cervical Cancer IAC Task Force 8 Summary, Chicago, Illinois, USA: Summary statement on quantitative cytochemistry, DNA and molecular biology): Task Force 8. Acta Cytol 45: 499-501, 2001 16. Feoli-Fonseca JC, Oligny LL, Filion M, et al: Two-tier polymerase chain reaction direct sequencing method for detecting an typing human papillomaviruses in pathological specimens. Diagn Mol Pathol 7: 317-323, 1998 17. Jacobs MV, Snijders PJ, van den Brule JC, et al: A general Primer GP5+/GP6+-Mediated PCR-Enzyme Immunoassay Method for Rapid Detection of 14 High-Risk and 6 Low-Risk Human Papillomavirus Genotypes in Cervical Scrapings. J Clin Microbiol 35: 791-795, 1997 18. Bauer HM, Greer CE, Manos MM: Determination of genital HPV infection using consensus PCR. In: Herrington CS and McGee JO, ed.): Diagnostic molecular pathology: a practical approach. Oxford University Press, Oxford, 1992 19. Duensing S, Duensing A, Flores ER, et al: Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol 75: 7712-7716, 2001 20. Skyldberg B, Fujioka K, Hellstrom AC, et al: Human papillomavirus infection, centrosome aberration and genetic stability in cervical lesions. Mod Pathol 14: 279-284, 2001 21. Southern SA, Herrington CS: Differential cell cycle regulation by low – and high-risk human papillomaviruses in low-grade squamous intraepithelial lesions of the cervix. Cancer Res 58: 2941- 2945, 1998 22. Giannoudis A, Evans MF, Southern SA, Herrington CS: Basal keratinocyte tetrasomy in low-grade squamous intra-epithelial lesions of the cervix is restricted to high and intermediate risk HPV infection but is not type-specific. Br J Cancer 82: 424-428, 2000 23. Hopman AH, Voorter CE, Ramaekers FC: Detection of genomic changes in cancer by in situ hybridization. Mol Biol Rep 19: 31-44, 1994 24. Bollmann R, Torka R, Schmitz J, et al: Determination of ploidy and steroid receptor status in breast cancer by laser scanning cytometry. Cytometry 50: 210-215, 2002 25. Atkin NB, Baker MC, Fox MF: Chromosome changes in 43 carcinomas of the cervix uteri. Cancer Genet Cytogenet 44: 229-241, 1990 26. Umayahara K, Numa F, Suehiro Y, et al: Comparative genomic hybridization detects genetic alterations during early stages of cervical cancer progression. Genes Chrom Cancer 33: 98-102, 2002 27. Kirchhoff M, Rose H, Petersen BL, et al: Comparative genomic hybridization reveals a recurrent pattern of chromosomal aberrations in severe dysplasia/carcinoma in situ of the cervic and in advanced stage cervical carcinoma. Genes Chromosomes Cancer 24: 144-150, 1999 28. Hidalgo A, Schewe C, Petersen S, et al: Human papillomavirus status and chromosomal imbalances in primary cervical carcinomas and tumour cell lines. Eur J Cancer 36: 542-548, 2000 29. Brink AATP, Wiegant JCAG, Szuhai K, et al: Simultaneous mapping of human papillomavirus integration sites and molecular karyotyping in short term cultures of cervical carcinomas by using 49- color combined binary ratio labeling fluorescence in situ hybridization. Cancer Genet Cytogenet 134: 145-150, 2002 30. Bulten J, Poddighe PJ, Robben JC,et al: Interphase cytogenetic analysis of cervical intraepithelial neoplasia. Am J Pathol 152: 495- 503, 1998 31. Aubele M, Zitzelsberger H, Schenck U, et al: Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser–assisted microdissection and comparative genomic hybridization. Cancer 84: 375-379, 1998
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 142
EP 148
PG 7
ER
PT J
AU Lorincz, T
Timar, J
Szendroi, M
AF Lorincz, Tamas
Timar, Jozsef
Szendroi, Miklos
TI Alterations of Microvascular Density in Bone Metastases of Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bone metastasis; microvessel density; breast cancer; lung cancer; renal cell cancer
ID bone metastasis; microvessel density; breast cancer; lung cancer; renal cell cancer
AB Bone may provide an extremely fertile microenvironment for angiogenesis. Experimental investigations indicate angiogenesis as a major regulator of bone metastasis development. Vascularization and angiogenic potential is known for most of the primary tumor types, but no studies investigated angiogenesis in bone metastases of human cancers. We have evaluated microvessel density of bone metastases of various cancer types (all adenocarcinomas) and compared to their primary tumors in paraffin samples of 39 patients. Microvessel density was determined by using the hot spot method and the blood vessel marker, CD34. The most vascularized adenocarcinoma was found to be renal cell cancer followed by lung adenocarcinoma, while breast cancer was heterogenous in this respect. Two patterns of modulation of the angiogenic phenotype in the bone metastases emerged in this study, which seemed to be cancer type specific: decreased angiogenic potential characterizing 45% of renal cell cancers and breast cancers of high vascularity in their primary, and increased angiogenic potential characterizing 40% of lung adenocarcinomas and breast cancers of low vascularity in their primary lesion. Our data demonstrate that i., the vascularization of bone metastases is frequently altered compared to the primary tumors, ii., patterns are different in the case of various cancer types. The tumor-type specific alterations of the angiogenic phenotype of cancers, metastatic to the bone, can have a clinical significance when angiosuppressive therapies are considered.
C1 [Lorincz, Tamas] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Hasan J, Byers R, Jayson GC. Intra-tumoral microvessel density in human solid tumours. Br J Cancer 86:1566-1577, 2002
Yoneda T. Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone. Eur J Cancer 34:240-245, 1998
Saaristo A, Karpanen T, Alitalo K. Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis. Oncogene 19:6122-6129, 2000
Winding B, Misander H, Sveigaard C et al. Human breast cancer induced angiogenesis, recruitment, and activation of osteoclasts in osteolytic metastasis. J Cancer Res Clin Oncol 126:631-640, 2000
Van der Pluijm G, Sijmons B, Vloedgraven H, et al: Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. J Bone Miner Res 16:1077-1091, 2001
Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer 80:1529-1537, 1997
Ellis LM, Liu W, Ahmad SA et al. Overview of angiogenesis: Biologic implications for antiangiogenic therapy. Semin Oncol 28:94-104, 2001
Kovacs L, Szende B, Elek G et al. Working experience with a new vacuum-accelerated microwave histoprocessor. J Pathol 180:106-110, 1996
Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1-8, 1991
Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584-593, 2002
Yang JC, Haworth L, Sherry RM et al. A randomised trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427-434, 2003
Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-23342, 2004.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 149
EP 153
PG 5
ER
PT J
AU Amirghofran, Z
Monabati, A
Khezri, A
Malek-Hosseini, Z
AF Amirghofran, Zahra
Monabati, Ahmad
Khezri, Abdolaziz
Malek-Hosseini, Zahra
TI Apoptosis in Transitional Cell Carcinoma of Bladder and its Relation to Proliferation and Expression of P53 and Bcl-2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Transitional cell carcinoma of bladder; apoptosis; bcl-2; p53
ID Transitional cell carcinoma of bladder; apoptosis; bcl-2; p53
AB Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among men. Tumor progression is associated with expression or modulation of several gene products that control apoptosis and proliferation. Apoptosis is a negative growth regulatory mechanism in tumors. The aim of this study is to examine apoptosis and related regulatory molecular markers in a group of patients with TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was detected by TUNEL method. Correlation between apoptotic index (AI), proliferation index (PI) and bcl-2 and p53 expression with each other and with pathological grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI of all cases was 13.7±24. No correlation was found between apoptosis and differentiation status of carcinoma. Bcl-2 expression was weakly detected in only one sample. P53 expression was detected in 26 of cases with mean staining index of 102±96. A significant correlation between p53 and Ki-67 staining indices was observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good association with the pathological grade (p=0.0001 and p=0.004, respectively). None of the markers showed significant correlation with AI and no correlation was found between the ratio of AI to PI and other parameters either. In conclusion, the frequency of apoptosis in TCC of bladder appears not to be associated with tumor grade, and with bcl-2, p53 and Ki-67 expression.
C1 [Amirghofran, Zahra] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Monabati, Ahmad] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Khezri, Abdolaziz] Medical School, Shiraz University of Medical Sciences, Department of UrologyShiraz, Iran.
[Malek-Hosseini, Zahra] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Amirghofran, Z (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
CR Hickman JA. Apoptosis and tumorigenesis. Curr Opin Genet Dev 12:67-72, 2002
Rossi D, Gaidano G. Messengers of cell death: apoptotic signaling in health and disease. Haematologica 88:212-218, 2003
Burlacu A. Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med 7:249-257, 2003
Batinac T, Gruber F, Lipozencic J et al. Protein p53—structure, function, and possible therapeutic implications. Acta Dermatovenerol Croat 11:225-230, 2003
Laiho M, Latonen L. Cell cycle control, DNA damage checkpoints and cancer. Ann Med 35:391-397, 2003
Sherr CJ. Principles of tumor suppression. Cell 23; 116:235- 246, 2004
Rodriguez-Alonso A, Pita-Fernandez S, Gonzalez-Carrero J, Nogueira-March JL: Multivariate analysis of survival, recurrence, progression and development of metastasis in T1 and T2a transitional cell bladder carcinoma. Cancer 15; 94:1677- 1684, 2002
Lin Z, Kim H, Park H, et al. The expression of bcl-2 and bcl- 6 protein in normal and malignant transitional epithelium. Urol Res 31:272-275, 2003
Yu DS, Chang SY. The expression of oncoproteins in transitional cell carcinoma: its correlation with pathological behavior, cell cycle and drug resistance. Urol Int 69:46-50, 2002
Llopis J, Alcaraz A, Ribal MJ, et al. p53 expression predicts progression and poor survival in T1 bladder tumors. Eur Urol 37:644-653, 2000
World Health Organization. Histological typing of urinary bladder tumors. 10, 1973
Budd RC. Activation-induced cell death. Curr Opin Immunol 13:356-362, 2001
King ED, Matteson J, Jacobs SC, Kyprianou N. Incidence of apoptosis, cell proliferation and bcl-2 expression in transitional cell carcinoma of the bladder: association with tumor progression. J Urol 155:316-320, 1996
Korkolopoulou P, Konstantinidou AE, Christodoulou P, et al. Apoptosis in bladder carcinomas detected with monoclonal antibody to single-stranded DNA: relation to cell cycle regulators and survival. Urology 1; 56:516-520, 2000
Roman S, Petrusca D, Moldovan I, et al. Evaluation of apoptosis of tumor and of apparently normal cells in human renal carcinoma. Immunol Lett 15; 67:15-22, 1999
Kong C, Zhang X, Takenaka I. Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter. Int J Urol 8:386-390, 2001
Zhang X, Kong C, Takenaka I. Evaluation of cell proliferation, apoptosis, and angiogenesis in transitional cell carcinoma of the renal pelvis and ureter. Urology 57:981-985, 2001
Townson JL, Naumov GN, Chambers AF. The role of apoptosis in tumor progression and metastasis. Curr Mol Med 3:631- 642, 2003
Vermeulen K, Berneman ZN, Van Bockstaele DR. Cell cycle and apoptosis. Cell Prolif 36165-36175, 2003
Bargonetti J, Manfredi JJ. Multiple roles of the tumor suppressor p53. Curr Opin Oncol 14:86-91, 2002
Lu QL, Abel P, Foster CS, Lalani EN. bcl-2: role in epithelial differentiation and oncogenesis. Hum Pathol 27:102-110, 1996
Uchida T, Minei S, Gao JP, et al. Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder. Oncol Rep 9:253-9, 2002
Ong F, Moonen LM, Gallee MP, et al. Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53. Radiother Oncol 61:169-175, 2001
Asci R, Yildiz L, Sarikaya S, et al. p53 and bcl-2 overexpression as associated risk factors in patients 40 years old or less with transitional cell carcinoma of the bladder. Urol Int 67:34- 40, 2001
Kirsh EJ, Baunoch DA, Stadler WM. Expression of bcl-2 and bcl-X in bladder cancer. J Urol 159:1348-1353, 1998
Pfister C, Flaman JM, Dunet F, et al. p53 mutations in bladder tumors inactivate the transactivation of the p21 and Bax genes, and have a predictive value for the clinical outcome after bacillus Calmette-Guerin therapy. J Urol 162:69-73, 1999
Harada H, Grant S. Apoptosis regulators. Rev Clin Exp Hematol 7:117-138, 2003
Smith ND, Rubenstein JN, Eggener SE, Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol 169: 1219-1228, 2003
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 154
EP 159
PG 6
ER
PT J
AU Hegyi, L
Hockings, DP
Benson, GM
Busza, LA
Overend, P
Grimsditch, CD
Burton, JK
Lloyd, H
Whelan, AG
Skepper, NJ
Vidgeon-Hart, PM
Carpenter, TA
Reid, GD
Suckling, EK
Weissberg, LP
AF Hegyi, Laszlo
Hockings, D Paul
Benson, G Martin
Busza, L Albert
Overend, Philip
Grimsditch, C David
Burton, J Katherine
Lloyd, Heather
Whelan, A Greg
Skepper, N Jeremy
Vidgeon-Hart, P Martin
Carpenter, T Adrian
Reid, G David
Suckling, E Keith
Weissberg, L Peter
TI Short Term Arterial Remodelling in the Aortae of Cholesterol Fed New Zealand White Rabbits Shown in vivo by High-Resolution Magnetic Resonance Imaging - Implications for Human Pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE animal models of human disease; imaging; MRI; atherosclerosis; remodelling
ID animal models of human disease; imaging; MRI; atherosclerosis; remodelling
AB High-resolution, non-invasive imaging methods are required to monitor progression and regression of atherosclerotic plaques. We investigated the use of MRI to measure changes in plaque volume and vessel remodelling during progression and regression of atherosclerosis in New Zealand White rabbits. Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. MR images (2D) of the abdominal aorta were acquired with cardiac and respiratory gating using a fast spin echo sequence with and without fat-suppression. In an initial study on rabbits treated for 30 weeks we imaged the aortae with a spatial resolution of 250x250 micrometers with a slice thickness of 2 mm and achieved a close correlation between MRI-derived measurements and those made on perfusion pressure-fixed histological sections (r1= 0.83, slope p1 < 0.01). We subsequently imaged 18 rabbits before and periodically during 12 weeks of cholesterol feeding (progression) followed by 12 weeks on normal diet (regression). Aortic wall (atherosclerotic lesion) volume increased significantly during progression and decreased during regression. In contrast, lumen volume increased during progression and did not change during regression. In conclusion, this study confirms that non-invasive, high-resolution MRI can be used to monitor progression and regression of atherosclerosis, each within 3 months and shows, for the first time in a short-term model, that positive remodelling occurs early during progression and persists through regression of atherosclerotic lesions.
C1 [Hegyi, Laszlo] University of Cambridge, Department of Medicine, Division of Cardiovascular Medicine, Hammersmith Hospital, Du Cane Road, W12 0HS Cambridge, UK.
[Hockings, D Paul] GlaxoSmithKline, Imaging GroupThe Frythe, Welwyn, UK.
[Benson, G Martin] GlaxoSmithKline, Atherosclerosis DepartmentStevenage, Hertfordshire, UK.
[Busza, L Albert] GlaxoSmithKline, Imaging GroupThe Frythe, Welwyn, UK.
[Overend, Philip] GlaxoSmithKline, Atherosclerosis DepartmentStevenage, Hertfordshire, UK.
[Grimsditch, C David] GlaxoSmithKline, Atherosclerosis DepartmentStevenage, Hertfordshire, UK.
[Burton, J Katherine] GlaxoSmithKline, Laboratory Animal SciencesThe Frythe, Welwyn, UK.
[Lloyd, Heather] GlaxoSmithKline, Laboratory Animal SciencesThe Frythe, Welwyn, UK.
[Whelan, A Greg] GlaxoSmithKline, Laboratory Animal SciencesThe Frythe, Welwyn, UK.
[Skepper, N Jeremy] University of Cambridge, Department of Anatomy, Multi-Imaging CentreCambridge, UK.
[Vidgeon-Hart, P Martin] GlaxoSmithKline, Atherosclerosis DepartmentStevenage, Hertfordshire, UK.
[Carpenter, T Adrian] University of Cambridge, Wolfson Brain Imaging CentreCambridge, UK.
[Reid, G David] GlaxoSmithKline, Imaging GroupThe Frythe, Welwyn, UK.
[Suckling, E Keith] GlaxoSmithKline, Atherosclerosis DepartmentStevenage, Hertfordshire, UK.
[Weissberg, L Peter] University of Cambridge, Department of Medicine, Division of Cardiovascular Medicine, Hammersmith Hospital, Du Cane Road, W12 0HS Cambridge, UK.
RP Hegyi, L (reprint author), University of Cambridge, Department of Medicine, Division of Cardiovascular Medicine, W12 0HS Cambridge, UK.
EM lhegyi@doctors.org.uk
CR Tadrous PJ: Methods for imaging the structure and function of living tissues and cells: 3. Confocal microscopy and microradiology. J Pathol 191:345-354, 2000.
Kobayashi N, Hosoya T, Adachi M, et al: Virtual MR microscopy for unruptured aneurysm. Comput Methods Programs Biomed 66:99-103, 2001
Cova M, Toffanin R: MR microscopy of hyaline cartilage: current status. Eur Radiol 12:814-823, 2002
Ezawa H, Yoneyama R, Kandatsu S, et al: Introduction of autopsy imaging redefines the concept of autopsy: 37 cases of clinical experience. Pathol Int 53:865-873, 2003
Thali MJ, Yen K, Vock P, et al: Image-guided virtual autopsy findings of gunshot victims performed with multi-slice computed tomography and magnetic resonance imaging and subsequent correlation between radiology and autopsy findings. Forensic Sci Int 138:8-16, 2003
Glagov S, Weisenberg E, Zarins CK, et al: Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371-1375, 1987
Fayad ZA, Fallon JT, Shinnar M, et al: Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice. Circulation 98:1541- 1547, 1998
McConnell MV, Aikawa M, Maier SE, et al: MRI of rabbit atherosclerosis in response to dietary cholesterol lowering. Arterioscler Thromb Vasc Biol 19:1956-1959, 1999
Fayad ZA, Nahar T, Fallon JT, et al: In vivo magnetic resonance evaluation of atherosclerotic plaques in the human thoracic aorta: a comparison with transesophageal echocardiography. Circulation 101:2503-2509, 2000
Worthley SG, Helft G, Fuster V, et al: Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation 101:586-589, 2000
Kolodgie FD, Katocs AS Jr, Largis EE, et al: Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol. Methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type. Arterioscler Thromb Vasc Biol 16:1454-1464, 1996
Groot PH, van Vlijmen BJ, Benson GM, et al: Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure. Arterioscler Thromb Vasc Biol 16:926-933, 1996
Stary HC, Chandler AB, Dinsmore RE, et al: A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92:1355-1374, 1995
Helft G, Worthley SG, Fuster V, et al: Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits. J Am Coll Cardiol 37:1149-1154, 2001
Trouard TP, Altbach MI, Hunter GC, et al: MRI and NMR spectroscopy of the lipids of atherosclerotic plaque in rabbits and humans. Magn Reson Med 38:19-26, 1997
Hockings PD, Roberts T, Galloway GJ, et al: Repeated threedimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice. Circulation 106:1716-1721, 2002
Helft G, Worthley SG, Fuster V, et al: Progression and regression of atherosclerotic lesions: monitoring with serial noninvasive magnetic resonance imaging. Circulation 105:993-998, 2002
Choudhury RP, Aguinaldo JG, Rong JX, et al: Atherosclerotic lesions in genetically modified mice quantified in vivo by noninvasive high-resolution magnetic resonance microscopy. Atherosclerosis 162:315-321, 2002
Saito D, Oka T, Kajiyama A, et al: Factors predicting compensatory vascular remodelling of the carotid artery affected by atherosclerosis. Heart 87:136-139, 2002
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 159
EP 165
PG 7
ER
PT J
AU Pires, RF
Perez, EdCD
de Almeida, PO
Kowalski, PL
AF Pires, Ramoa Fabio
Perez, Elias da Cruz Danyel
de Almeida, Paes Oslei
Kowalski, Paulo Luiz
TI Estrogen Receptor Expression in Salivary Gland Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mucoepidermoid carcinoma; adenoid cystic carcinoma; salivary gland tumors; immunohistochemistry; estrogen; estrogen receptor
ID mucoepidermoid carcinoma; adenoid cystic carcinoma; salivary gland tumors; immunohistochemistry; estrogen; estrogen receptor
AB Estrogen receptor (ER) expression in salivary gland carcinomas is controversial, and most published studies considered no more than 10 cases. We analyzed ER expression by immunohistochemistry in 136 mucoepidermoid carcinomas and 72 adenoid cystic carcinomas. All cases were negative. These results do not support a role for estrogens in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma.
C1 [Pires, Ramoa Fabio] School of Dentistry, State University of Rio de Janeiro, Oral PathologyRio de Janeiro, Brazil.
[Perez, Elias da Cruz Danyel] State University of Campinas, School of Dentistry, Department of Oral DiagnosisPiracicaba, Brazil.
[de Almeida, Paes Oslei] State University of Campinas, School of Dentistry, Department of Oral DiagnosisPiracicaba, Brazil.
[Kowalski, Paulo Luiz] A. C. Camargo Cancer Hospital, Department of Head and Neck Surgery and Otorhinolaryngology, Rua Prof Antonio Prudente, 211, Liberdade, 01509-900 Sao Paulo, Brazil.
RP Kowalski, PL (reprint author), A. C. Camargo Cancer Hospital, Department of Head and Neck Surgery and Otorhinolaryngology, 01509-900 Sao Paulo, Brazil.
EM lp_kowalski@uol.com.br
CR Arpino G, Clark GM, Mohsin S, et al: Adenoid cystic carcinoma of the breast: molecular markers, treatment, and clinical outcome. Cancer 94: 2119-2227, 2002
Barnes L, Rao U, Contis L, et al: Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein. Oral Surg Oral Med Oral Pathol 78: 74-80, 1994
Dimery IW, Jones LA, Verjan RP, et al: Estrogen receptors in normal salivary gland and salivary gland carcinoma. Arch Otolaryngol Head Neck Surg 113: 1082-1085, 1987
Dori S, Trougouboff P, David R, Buchner A: Immunohistochemical evaluation of estrogen and progesterone receptors in adenoid cystic carcinoma of salivary gland origin. Oral Oncol 36: 450-453, 2000
Ellis GL, Auclair P: Tumors of the Salivary Glands. Atlas of Tumor Pathology, 3rd Series, Fascicle 17, eds). Washington, DC: Armed Forces Institute of Pathology, 1996
Gaffney EV, Pinkston JA, Eidson JJ: Estrogen receptors in parotid tumors. Endocr Res 21: 635-643, 1995
Glas AS, Hollema H, Nap RE, Plukker JT: Expression of estrogen receptor, progesterone receptor, and insulin-like growth factor receptor-1 and of MIB-1 in patients with recurrent pleomorphic adenoma of the parotid gland. Cancer 94: 2211-2216, 2002
Jeannon JP, Soames JV, Bell H, Wilson JA: Immunohistochemical detection of oestrogen and progesterone receptors in salivary tumours. Clin Otolaryngol 24: 52-54, 1999
Lamey PJ, Leake RE, Cowan SK, et al: Steroid hormone receptors in human salivary gland tumours. J Clin Pathol 40: 532- 534, 1987
Miller AS, Hartman GG, Chen SY, et al: Estrogen receptor assay in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of salivary gland origin. An immunohistochemical study. Oral Surg Oral Med Oral Pathol 77: 36- 40, 1994
Nasser SM, Faquin WC, Dayal Y: Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors. Frequent expression of androgen receptor in a subset of malignant salivary gland tumors. Am J Clin Pathol 119: 801-806, 2003
Ozono S, Sato K, Ito Y, et al: Immunohistochemical evidence that tumors elicit the synthesis of estrogen receptors in the submandibular gland of female rats. Experientia 51:220-222, 1995
Shick PC, Riordan GP, Foss RD: Estrogen and progesterone receptors in salivary gland adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80: 440-444, 1995
Wilson JA, Rogers MJC, Hawkins RA, et al: Epidermal growth factor receptors and oestrogen receptors in the head and neck. Clin Otolaryngol 18: 66-68, 1993
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 166
EP 168
PG 3
ER
PT J
AU Kovacs, J
Varga, A
Bessenyei, M
Gomba, Sz
AF Kovacs, Judit
Varga, Attila
Bessenyei, Maria
Gomba, Szabolcs
TI Renal Cell Cancer Associated with Sarcoid-like Reaction
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE renal cancer; sarcoid-like granuloma; immunohistochemistry
ID renal cancer; sarcoid-like granuloma; immunohistochemistry
AB An unusual granulomatous reaction within a conventional clear cell renal cancer in a 62 year-old woman is reported. Using immunohistochemical evaluation, cells of the granuloma were CD68 (Kp1), carboxypeptidase M and CD3 positive. No signs of sarcoidosis were found in other organs. According to the few publications that mention cancer associated sarcoid-like reaction, such lesions do not influence the prognosis. Our patient is still well for a 15 months follow-up.
C1 [Kovacs, Judit] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., H-4012 Debrecen, Hungary.
[Varga, Attila] University of Debrecen, Medical and Health Science Center, Department of UrologyDebrecen, Hungary.
[Bessenyei, Maria] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., H-4012 Debrecen, Hungary.
[Gomba, Szabolcs] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., H-4012 Debrecen, Hungary.
RP Kovacs, J (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4012 Debrecen, Hungary.
CR Marinides GN, Hajdu I, Gand RO: A unique association of renal cell carcinoma with sarcoid reaction in the kidney. Nephron 67:477-480, 1994
Ryska A, Seifert G: Adenolymphoma, Whartin’s tumor, with multiple sarcoid-like granulomas. Pathol Res Pract 195:835- 839, 1999
Ludvikova M, Ryska A and Drovakova E: Focal sarcoid-like change of the thyroid gland. A possible consequence of aspiration cytology? Pathol Res Pract 198:479-482, 2002
Moder KG, Litin SC and Gaffey TA: Renal cell carcinoma associated with sarcoid-like tissue reaction. Mayo Clin Proc 65:1498-1501, 1990
Bottone AC, Labarbera M, Asasourian A et al: Renal sarcoidosis coexisting with hypernephroma. Urology 41:157-159, 1993
Campbell F and Douglas-Jones AG: Sarcoid-like granulomas in primary renal cell carcinoma. Sarcoidosis 10:128-131, 1992
Lucci S, Rivolta R and Fazi M: Sarcoidosis and clear cell carcinoma of the kidney: the sixth case? G Chir 23:75-78, 2002
Shigematsu H, Kurita A, Omura Y et al: Gastric cancer with sarcoid reactions in the regional lymphnodes, the stomach and the splenic parenchyma. Report of a case. Surgery Today- Tokyo 29:549-552, 1999
Kamiyoshihara M, Hirai T and Kawashima O: Sarcoid reactions in primary pulmonary carcinoma. Report of seven cases. Oncology Reports 5:177-180, 1998
Bassler K and Birke F: Histopathology of tumor associated sarcoid- like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigation. Virchows Arch A Pathol Anat Histopathol 412:231-239, 1988
Rayson D, Burch PA and Richardson RL: Sarcoidosis and testicular carcinoma. Cancer 83:337-343, 1998
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 169
EP 171
PG 3
ER
PT J
AU Brittig, F
Weinkauf, P
Karchner, H
AF Brittig, Ferenc
Weinkauf, Philip
Karchner, Hannelore
TI Ideal Cooling Process for Paraffin-Embedded Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE sectioning; paraffin block; cooling technique
ID sectioning; paraffin block; cooling technique
AB Back in the seventies everybody was convinced that it was no longer necessary to cool paraffinembedded tissues, because of the new advances in the production of paraffin. The reason for this assumption was the addition of plastic polymers and dimethyl sulfoxide. The quality of tissue sectioning improved because of these additives. The daily routine in the histology laboratories shows that it is impossible to produce good quality cutting without cooling. Cooling the paraffin by means of cooling plates or ice dishes creates drastic improvement; the cutting quality improves and it is much easier. Both improvements speed up the process and save time for the technicians and the physician. Long-term study indicates that not only the temperature but also the methodology of cooling and the cooling rate are playing a decisive role in the cutting quality.
C1 [Brittig, Ferenc] County Hospital, Department of Pathology, H-8200 Veszprem, Hungary.
[Weinkauf, Philip] Design engineerVeszprem, Hungary.
[Karchner, Hannelore] Design engineerVeszprem, Hungary.
RP Brittig, F (reprint author), County Hospital, Department of Pathology, H-8200 Veszprem, Hungary.
CR Lamb RA: Waxes for Histology, Histopathology), selected topics, Ed.: H. C. Cook. Lailliere Tindall, London, 1973
Arnold M: Histochemie, Leydenfrostisches Phanomen, Springer Verlag, 1968
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 172
EP 173
PG 2
ER
PT J
AU Sinkovics, GJ
AF Sinkovics, G Joseph
TI Chondrosarcoma Cell Differentiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE chondrocytes; chondrosarcoma cells; immune T cell; NK cell; cytotoxic lymphocytes; tumor cell differentiation; telomerase
ID chondrocytes; chondrosarcoma cells; immune T cell; NK cell; cytotoxic lymphocytes; tumor cell differentiation; telomerase
AB A mixed population of lymphocytes from a healthy donor co-existed with an established culture of allogeneic chondrosarcoma cells, during which time the tumor cells changed from malignantly transformed to benign fibroblast-like morphology; from multilayered to a monolayered growth pattern; lost their potency to grow in colonies in soft agar; and showed signs of senescence. A discussion of possible molecular mechanisms for this event is offered. If there are as yet undiscovered lymphokines that can induce reversal of the malignant geno/phenotype, the cognate gene(s) should be cloned for genetic engineering and for the mass production of the corresponding molecular mediators for clinical trials.
C1 [Sinkovics, G Joseph] The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-Immunology, Dr Martin Luther King Jr Blvd, 3001 W Tampa, FL, USA.
RP Sinkovics, GJ (reprint author), The University of South Florida College of Medicine, Departments of Medicine and Medical Microbiology-Immunology, 3001 W Tampa, USA.
CR Adams CS, Shapiro IM: The fate of the terminally differentiated chondrocyte: evidence for microenvironmental regulation of chondrocyte apoptosis. Crit Rev Oral Biol Med 13:465-473, 2002.
Aigner T, Loos S, Muller S et al.: Cell differentiation and matrix gene expression in mesenchymal chondrosarcomas. Am J Pathol 156:1327-1335, 2000.
Aigner, T., Dertinger, S., Belke, J., Kirchner, T: Chondrocytic cell differentiation in clear cell chondrosarcoma. Hum Pathol 27:1301-1305,1996
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2004
VL 10
IS 3
BP 174
EP 187
PG 14
ER
PT J
AU Gundy, S
Babosa, M
Baki, M
Bodrogi, I
AF Gundy, Sarolta
Babosa, Maria
Baki, Marta
Bodrogi, Istvan
TI Increased Predisposition to Cancer in Brothers and Offspring of Testicular Tumor Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE testicular cancer; familial cancer risk; childhood tumors
ID testicular cancer; familial cancer risk; childhood tumors
AB Cancer susceptibility was examined in first-degree relatives of 293 testicular tumor patients (TTPs) and 586 age-matched healthy males. Significantly increased risk was found in the families of TTPs (OR: 1.4; CI: 1.08-1.79), however, except for testicular cancer of 7 brothers (OR: 11.7; CI: 1.42-256.5), and 6 various childhood tumors (bilateral Wilms' tumor, neuroblastoma, medulloblastoma, ALL, histiocytosis-X, testicular tumor) of 200 offspring (OR: 12.9; CI: 1.54-286.2), no association with other malignancies was observed. No differences were seen between the fertility of patients and controls when occupational or socio-economic status of the families was taken into account. However, the majority of the controls (85%) fathered the first child between 20-30 years of age, while only 61% of TTPs had the first child in the same age group. TTPs fathered more girls than boys (P=0.009), and the lower male - higher female ratio of index children was also identical, irrespective of the conception taking place before or after the father’s treatment. Occupations did not, but smoking might have influenced cancer susceptibility of the patients. Aggregation of fraternal testicular tumors, and both dramatically increased cancer risk and altered sex ratio of the offspring indicate a remarkable role of hereditary factors in tumorigenesis and later consequences of a certain portion of testicular malignancies, which must be refined by molecular studies.
C1 [Gundy, Sarolta] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Babosa, Maria] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Baki, Marta] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Bodrogi, Istvan] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
RP Gundy, S (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
EM gundy@oncol.hu
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Knudson AGJ, Strong LC: Mutation and cancer: neuroblastoma and pheochromocytoma. Am J Hum Genet 24: 514-522, 1972
Kim E, Nichols KE, Malkin D, et al: Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidem Biom Prev 10: 83-87, 2001
Heimdal K, Lothe RA, Lystad S, et al: No germ line TP53 mutations detected in familial and bilateral testicular cancer. Genes Chromosomes Cancer 6: 92-97, 1993
Jones RH, Vasey P: New directions in testicular cancer; molecular determinants of oncogenesis and treatment success. Eur J Cancer 39: 147-156, 2003
Peltomaki P, Lothe R, Borresen AL, et al: Altered dosage of the sex chromosomes in human testicular cancer: a molecular genetic study. Int J Cancer 47: 518-522, 1991
Moller H: Trends in sex-ratio, testicular cancer and male reproductive hazards: Are they connected? APMIS 106: 232- 239, 1998
Moller H, Skakkebaek NE: Risk of testicular cancer in subfertile men. Br Med J 318: 559-562, 1999
Fossa SD, Kravdal O: Fertility in Norwegian testicular cancer patients. Br J Cancer 82: 737-741, 2000
Demographic Yearbook. Hungarian Central Statistical Office, 2003, Budapest
Hemminki K, Vaittinen P, Dong C, Easton D: Sibling risks in cancer: clues to recessive or X-linked genes? Br J Cancer 84: 388-391, 2001
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 197
EP 203
PG 7
ER
PT J
AU Kida, A
Ohashi, K
Kobayashii, T
Sakai, M
Yamashita, T
Akiyama, H
Kishida, Sh
Sakamaki, H
AF Kida, Aiko
Ohashi, Kazuteru
Kobayashii, Takeshi
Sakai, Miwa
Yamashita, Takuya
Akiyama, Hideki
Kishida, Shuji
Sakamaki, Hisashi
TI Incapacitating Lower Limb Pain Syndrome in Cord Blood Stem Cell Transplant Recipients with Calcineurin Inhibitor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE calcineurin inhibitor; lower limb pain; pruritus; cord blood stem cell transplantation
ID calcineurin inhibitor; lower limb pain; pruritus; cord blood stem cell transplantation
AB Calcineurin-inhibitor induced pain syndrome (CIPS) is a newly described entity with a characteristic feature of sudden onset of severe lower limb pain, and high levels of cyclosporine or tacrolimus may be involved in the pathogenesis. This syndrome is rarely seen in recipients of hematopoietic stem cell transplantation (HSCT) compared with other organ transplant recipients, however, heightened awareness of this complication after HSCT may be needed for hematologists, as misdiagnosis can result in catastrophic consequences. We report herein two cases of lower limb pain syndrome, with some clinical features resembling CIPS, occurring during the early phase of cord blood stem cell transplantation for hematological malignancy.
C1 [Kida, Aiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashii, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakai, Miwa] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Yamashita, Takuya] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Akiyama, Hideki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kishida, Shuji] Tokyo Metropolitan Komagome Hospital, Neurology DivisionTokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Ohashi, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM k.ohashi@cick.jp
CR Kunzendorf U, Brockmoller J, Jochimsen F, et al: Cyclosporin metabolites and central-nervous-system toxicity. Lancet 1: 1223-1223, 1988
Walker RW, Brochstein JA: Neurologic complications of immunosuppressive agents. Neurol Clin 6: 261-278, 1988
Reece DE, Frei-Lahr DA, Shepherd JD, et al: Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. Bone Marrow Transplant 8: 393-401, 1991
Bechstein WO: Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transpl Int 13: 313-326, 2000
Grotz WH, Breitenfeldt MK, Braune SW, et al: Calcineurininhibitor induced pain syndrome, CIPS): a severe disabling complication after organ transplantation. Transpl Int 14: 16-23, 2001
Lucas VP, Ponge TD, Plougastel-Lucas ML, et al: Musculoskeletal pain in renal-transplant recipients. N Engl J Med 325: 1449-1450, 1991
Sanches EN, Criado AB, Guajardo AS, et al: Leg bone pain syndrome due to cyclosporine in a renal transplant patient. Clin Exp Rheum 12: 653-656, 1994
Gauthier VJ, Barbosa LM: Bone pain in transplant recipients responsive to calcium channel blockers. Ann Intern Med 121: 863-865, 1994
Stevens JM, Hilson AJW, Sweny P: Post-renal transplant distal limb bone pain. Transplantation 60: 305-307, 1995
Goffin E, Vande Berg B, Pirson Y, et al: Epiphyseal impaction as a cause of severe osteoarticular pain of lower limbs after renal transplantation. Kidney Int 44: 98-106, 1993
Villaverde V, Cantalejo M, Balsa A, et al: Leg bone pain syndrome in a kidney transplant patient treated with tacrolimus, FK506). Ann Rheum Dis 58: 653-654, 1999
Malat GE, Dupuis RE, Kassman B, et al: Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient. Pediatr Transplant 6: 435-438, 2002
Blombery PA: A review of reflex sympathetic dystrophy. Aust Fam Physician 24: 1651-1655, 1995
Munoz-Gomez J, Collado A, Gratacos J, et al: Reflex sympathetic dystrophy syndrome of the lower limbs in renal transplant patients treated with cyclosporin A. Arthritis Rheum 34: 625-630, 1991
Shinoda K, Sugiyama E, Taki H, et al: Resting T cells negatively regulate osteoclast generation from peripheral blood monocytes. Bone 33: 711-720, 2003
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 204
EP 206
PG 3
ER
PT J
AU Surowiak, P
Paluchowski, P
Wysocka, T
Wojnar, A
Zabel, M
AF Surowiak, Pawel
Paluchowski, Piotr
Wysocka, Teresa
Wojnar, Andrzej
Zabel, Maciej
TI Steroid Receptor Status, Proliferation and Metallothionein Expression in Primary Invasive Ductal Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; hormone receptor status; metallothionein; Ki-67
ID Breast cancer; hormone receptor status; metallothionein; Ki-67
AB The most important immunocytochemical prognostic and predictive factors in cases of breast cancer include estrogen receptor alpha (ER) and progesterone receptor (PgR). The present study aimed at examining the relationship between the manifestation intensity of proliferation markers (Ki-67 and nucleolar organizer regions - AgNORs) on one hand, and expression of ER and PgR on the other in a uniform group of invasive ductal breast cancers of G2 grade. Moreover, the study aimed at examining the relationship between the above mentioned markers and expression of metallothionein (MT). The studies were performed on samples of invasive ductal breast cancers of G2 grade, originating from 60 females. In paraffin sections originating from the studied cases immunocytochemical reactions were performed using monoclonal antibodies to ER, PgR, Ki-67 and MT, and silver staining was conducted to localize AgNORs. The obtained results were subjected to statistical analysis using Statistica software. Results indicate that manifestation of AgNORs does not correlate with any of the studied antigens (ER, PgR, Ki-67, MT) (p>0.05). Moreover, no relationship could be demonstrated between the intensity of MT expression and proliferation markers or steroid receptor status (p>0.05). A negative correlation was shown between the expression of ER and Ki-67 (p=0.0009). The most intense proliferative activity was demonstrated in cases of breast cancer showing PgR expression but no ER expression (p=0.015), while the lowest proliferative activity was detected in breast cancers with expression of both ER and PgR (p<0.05).
C1 [Surowiak, Pawel] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a,, 50-356 Wroclaw, Poland.
[Paluchowski, Piotr] Regio Hosptital PinnebergPinneberg, Germany.
[Wysocka, Teresa] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a,, 50-356 Wroclaw, Poland.
[Wojnar, Andrzej] Regio Hosptital PinnebergPinneberg, Germany.
[Zabel, Maciej] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a,, 50-356 Wroclaw, Poland.
RP Surowiak, P (reprint author), Wroclaw Medical University, Department of Human Morphology and Embryology, 50-356 Wroclaw, Poland.
CR Biesterfeld S, Farokhzad F, Klueppel D, et al: Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment. Virchows Arch 438: 478-484, 2001
Clahsen PC, Van de Velde CJH, Duval C, et al: The utility of mitotic index, oestrogen receptor and Ki67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol 25: 356-363, 1999
Detreb S, King N, Salter J, et al: Immunohistochemical and biochemical analysis of the oestrogen regulated protein pS2, and its relation with oestrogen receptor and progesterone receptor in breast cancer. J Clin Pathol 47: 240-244, 1994
Fitzgibbons PL, Page DL, Weaver D, et al: Prognostic factors in breast cancer. College of American Pathologist consensus statement 1999. Arch Pathol Lab Med 124: 966-978, 2000
Friedline JA, Garret SH, Somji S, et al: Differential expression of the MT-1E gene in estrogen-receptor-positive and -negative human breast cancer cell lines. Am J Pathol 152: 23-27, 1998
Harris H, Henderson RA, Bhat RA, Komm BS: Regulation of metallothionein II messenger ribonucleic acid measures exogenous estrogen receptor beta activity in SAOS-2 and LNCaPLN3 cells. Endocrinology 142: 645-652, 2001
Hishikawa Y, Koji T, Dhar DK, et al: Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus. Br J Cancer 81: 712-720, 1999
Ioachim E, Assimakopoulos D, Peschos D, et al: Immunohistochemical expression of metallothionein in benign, premalignant and malignant epithelium of the larynx: correlation with p53 and proliferative cell nuclear antigen. Pathol Res Pract 195: 809-814, 1999
Jensen EV, Cheng G, Palimieri C, et al: Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc Natl Acad Sci USA 98: 15197-15202, 2001
Jin R, Bay BH, Chow VT, Tan PH: Metallothionein 1F mRNA expression correlates with histological grade in breast carcinoma. Breast Cancer Res Treat 66: 265-272, 2001
Jin R, Chow VT, Tan PH, et al: Metallothionein 2A expression is associated with cell proliferation in breast cancer. Carcinogenesis 23: 81-86, 2002
Kagi JHR: Overview of metallothionein. Methods Enzymol 205: 613-626, 1991
Keshigan AA, Cnaan A: Estrogen receptor-negative, progesterone receptor-positive breast carcinoma. Poor clinical outcome. Arch Pathol Lab Med 120: 970-973, 1996
Ploton D, Menager M, Jeannesson P, et al: Improvement in the staining and in the visualisation of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histochem J 18: 5-14, 1986
Remmele W, Stegner HE: Recommendation for uniform definition of an immunoreactive score, IRS, for immunohistochemical estrogen receptor detection, ER-ICA, in breast cancer tissue. Pathologe 8: 138-140, 1987
Schmidt CJ, Hamer DH: Cell specificity and an effect of ras on human metallothionein gene expression. Proc Natl Acad Sci USA 83: 3346-3350, 1986
Schwint A, Folco A, Morales A, et al: AgNOR mark epithelial foci in malignant transformation in hamster cheek pouch carcinogenesis. J Oral Pathol Med 25: 20-24, 1996
Surowiak P, Dzizgiel P, Zabel M, et al: Analysis of estrogen receptor, ER, and estrogen-dependent pS2 protein expression in cells of mammary ductal carcinoma. Fol Histochem Cytobiol 39: 145-146, 2001
Zas³awski R, Surowiak P, Dziegiel P, et al: Analysis of the expression of estrogen and progesterone receptors, and of PCNA and Ki67 proliferation antigens, in uterine myomata cells in relation to the phase of the menstrual cycle. Med Sci Monit 7: 784-789, 2001
Zhang R, Zhang H, Wei H, Luo X: Expression of metallothionein in invasive ductal breast cancer in relation to prognosis. J Environ Pathol Toxicol Oncol 19: 95-97, 2000
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 207
EP 211
PG 5
ER
PT J
AU Wu, D
Qiao, Y
Kristensen, BG
Li, Sh
Troen, G
Holm, R
Nesland, MJ
Suo, Z
AF Wu, Dan
Qiao, Yuhuan
Kristensen, B Gunnar
Li, Shanshan
Troen, Gunhild
Holm, Ruth
Nesland, M Jahn
Suo, Zhenhe
TI Prognostic Significance of Dysadherin Expression in Cervical Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE dysadherin; squamous cell cervical carcinoma; immunohistochemistry; RT-PCR; laser capture microdissection
ID dysadherin; squamous cell cervical carcinoma; immunohistochemistry; RT-PCR; laser capture microdissection
AB The protein and mRNA expression of dysadherin was studied in a series of squamous cell cervical carcinomas, and their clinicopathological associations and prognostic value were explored. Immunohistochemistry was used to assess protein expression of dysadherin in 206 patients with squamous cell cervical carcinoma, FIGO stage Ia-IVb. Frozen tissues from 20 cases in which the tumors showed variable dysadherin protein expression were used for laser capture microdissection (LCM) and processed for RTPCR detection of dysadherin mRNA. Immunohistochemically, all the dysadherin-positive staining was membranous. Positive cell membranous dysadherinpositive staining was often observed at the edge of tumor nests, although strong immunoreactivity throughout whole tumor nests was also seen in some tumors. Basal cells of the normal cervical epithelia were positive for dysadherin while its expression in the squamous cell cervical carcinomas was variable. Among the 206 tumors, 23 (11.2%) were negative, 53 (25.7%) were scored 1+, 54 (26.2%) were scored 2+ and 76 (36.9%) were scored 3+. In the 20 tumors analyzed, mRNA expression of dysadherin basically corresponded to its protein expression. No significant correlation between expression of dysadherin and age, FIGO stage or lymph node status was observed. Higher level of dysadherin expression, however, was significantly associated with shorter overall survival (p=0.04). We conclude that there is dysadherin protein expression in basal and parabasal cells of normal cervical epithelia, and higher level of dysadherin protein expression in squamous cell cervical carcinoma is predictive of a shorter overall survival, indicating that dysadherin may be a valuable prognostic marker in cervical carcinoma.
C1 [Wu, Dan] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, Montebello, 0310 Oslo, Norway.
[Qiao, Yuhuan] The First Teaching Hospital, Zhengzhou University, Department of Obstetrics and GynecologyHenan, China.
[Kristensen, B Gunnar] The Norwegian Radium Hospital, University of Oslo, Department of Gynecologic OncologyOslo, Norway.
[Li, Shanshan] The First Teaching Hospital, Zhengzhou University, Department of PathologyHenan, China.
[Troen, Gunhild] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, Montebello, 0310 Oslo, Norway.
[Holm, Ruth] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, Montebello, 0310 Oslo, Norway.
[Nesland, M Jahn] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, Montebello, 0310 Oslo, Norway.
[Suo, Zhenhe] The Norwegian Radium Hospital, University of Oslo, Department of Pathology, Montebello, 0310 Oslo, Norway.
RP Suo, Z (reprint author), The Norwegian Radium Hospital, University of Oslo, Department of Pathology, 0310 Oslo, Norway.
EM zhenhe.suo@labmed.uio.no
CR Jemal A, Murray T, Samuels A et al: Cancer statistics, 2003. CA Cancer J Clin 53:5-26, 2003
Flores-Luna L, Salazar-Martinez E, Escudero-De los Rios P et al: Prognostic factors related to cervical cancer survival in Mexican women. Int J Gynaecol Obstet 75:33-42, 2001
Kawagoe T, Kashimura M, Matsuura Y et al: Clinical significance of tumor size in stage IB and II carcinoma of the uterine cervix. Int J Gynecol Cancer 9:421-426, 1999
Hirohashi S, Kanai Y: Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575-581, 2003
Birchmeier W. E-cadherin as a tumor, invasion, suppressor gene. Bioessays 17:97-99, 1995
Christofori G, Semb H: The role of the cell-adhesion molecule E-cadherin as a tumor-suppressor gene. Trends Biochem Sci 24:73-76, 1999
Yoshiura K, Kanai Y, Ochiai A et al: Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA 92:7416-7419, 1995
Graff JR, Gabrielson E, Fujii H et al: Methylation patterns of the E-cadherin 5’ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem 275:2727-2732, 2000
Becker KF, Atkinson MJ, Reich U et al: E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 54:3845-3852, 1994
Matsuyoshi N, Hamaguchi M, Taniguchi S et al: Cadherinmediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol 118:703-714, 1992
Ino Y, Gotoh M, Sakamoto M et al: Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis. Proc Natl Acad Sci USA 99:365-370, 2002
Aoki S, Shimamura T, Shibata T et al: Prognostic significance of dysadherin expression in advanced colorectal carcinoma. Br J Cancer 88:726-732, 2003
Shimamura T, Sakamoto M, Ino Y et al: Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to e-cadherin expression. J Clin Oncol 21:659-667, 2003
Sato H, Ino Y, Miura A et al: Dysadherin: expression and clinical significance in thyroid carcinoma. J Clin Endocrinol Metab 88:4407-4412, 2003
Pecorelli S, Odicino F: Cervical cancer staging. Cancer J 9:390-394, 2003
Tsuiji H, Takasaki S, Sakamoto M et al: Aberrant O-glycosylation inhibits stable expression of dysadherin, a carcinomaassociated antigen, and facilitates cell-cell adhesion. Glycobiology 13:521-527, 2003
Adams CL, Nelson WJ, Smith SJ: Quantitative analysis of cadherin- catenin-actin reorganization during development of cellcell adhesion. J Cell Biol 135:1899-1911, 1996
Carico E, Atlante M, Bucci B et al: E-cadherin and alphacatenin expression during tumor progression of cervical carcinoma. Gynecol Oncol 80:156-161, 2001
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 212
EP 218
PG 7
ER
PT J
AU Sharma, ChM
Ralte, MA
Gaekwad, Sh
Santosh, V
Shankar, KS
Sarkar, Ch
AF Sharma, Chand Mehar
Ralte, Mercy Angela
Gaekwad, Shailesh
Santosh, Vani
Shankar, K S
Sarkar, Chitra
TI Subependymal Giant Cell Astrocytoma - a Clinicopathological Study of 23 Cases with Special Emphasis on Histogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tuberous sclerosis; SEGA; epilepsy; lateral ventricle tumor; immunohistochemistry
ID tuberous sclerosis; SEGA; epilepsy; lateral ventricle tumor; immunohistochemistry
AB Subependymal giant cell astrocytomas (SEGAs) are relatively rare tumors but occur commonly in the setting of the familial syndrome of tuberous sclerosis complex (TSC). In view of its varied morphology, i.e. resemblance to astrocytic and ganglion cells, its histogenesis remains controversial. We studied 23 cases of SEGA, 19 from our own institute and 4 from NIMHANS, Bangalore. These 19 cases of SEGAs were collected over a period of 23 years (1979 to 2001), and accounted for 0.16% of intracranial tumors and 0.51% of all gliomas reported at our center. The majority of patients presented with visual disturbances (19/23, 82.6%) in the form of decreased vision (60.8%) and blindness (21.7%), generalized tonic clonic seizures (43.4%) and focal motor seizures (4.37%). Age ranged from 4 to 37 years (mean 13.2 years) with male predominance (M:F 2.2:1), and the duration of symptoms varied from 1 month to 96 months (mean 17.2 months). Lateral ventricular involvement was the most common site (91.3%), followed by the third ventricle (8.6%). Nine patients (39.1%) had stigmata of tuberous sclerosis (6 at the time of diagnosis and 3 in the follow-up period). Two patients died due to surgical complications, while the rest were alive and well in the follow-up period ranging from 3 to 264 months (mean 37.1 months). Two patients experienced recurrences, one two years and another 22 years after surgery. Microscopic examination showed varied histology consisting of sweeping bundles of spindle cells, gemistocyte and ganglion-like cells with interspersed inflammatory cell component. The inflammatory cell component on special staining turned out to be an admixture of mast cells and T lymphocytes. Six cases showed areas of necrosis and/or mitosis, but were not indicative of aggressive nature of this tumor. Immunoreactivity for GFAP, NF, S-100, NSE and synaptophysin indicates that this is a hybrid tumor with glial and neuronal differentiation. None of the tumors was immunopositive for HMB-45. The significance of the presence of T lymphocytes and mast cells is not clear. It could be related to tumor immunology and may indicate a favorable prognosis.
C1 [Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Ralte, Mercy Angela] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Gaekwad, Shailesh] All India Institute of Medical Sciences, Department of NeuroradiologyNew Delhi, India.
[Santosh, Vani] National Institute of Mental Health and Neurosciences, Department of NeuropathologyBangalore, India.
[Shankar, K S] National Institute of Mental Health and Neurosciences, Department of NeuropathologyBangalore, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
CR Shepherd CW, Scheithauer BW, Gomez MR, et al: Subependymal giant cell astrocytoma: a clinical, pathological and flow cytometric study. Neurosurg 28: 868-864, 1991
Chow CW, Klug GL, Lewis EA: Subependymal giant cell astrocytoma in children: An unusual discrepancy between histological and clinical features. J Neurosurg 68: 880-883, 1988
Bonnin JM, Rubinstein LJ, Papasozomenos SC and Marangos PJ: Subependymal giant cell astrocytomas. Significance and possible cytogenetic implications of an immunohistochemical study. Acta Neuropathol 62: 185-193, 1984
Fuziwara S, Takaki T, Hikita T, Nishio S: Subependymal giant cell astrocytoma associated with tuberous sclerosis: do subependymal nodules grow? Child’s nervous system 5: 43- 44, 1989
Morimoto K, Mogami H: Sequential CT study of subependymal giant cell astrocytoma associated with tuberous sclerosis: case report. J Neurosurg 65: 874-877, 1986
Lopes MBS, Altermatt HJ, Scheithauer BW, et al: Immunohistochemical characterisation of subependymal giant cell astrocytomas. Acta Neuropathol 91: 368-375, 1996
Bender BL, Yunis EJ: Central nervous system pathology of tuberous sclerosis in children. Ultrastruct Pathol 1: 287-299, 1980
Halmagyi GM, Bignold LP, Allospi JP: Recurrent subependymal giant cell astrocytoma in the absence of tuberous sclerosis. J Neurosurg 50: 106-109, 1979
Sima AAF, Robertson DM: Subependymal giant cell astrocytoma. Case report with ultrastructural study. J Neurosurg 50: 240-245, 1979
Trombley IK, Mirra SS: Ultrastructure of tuberous sclerosis: cortical tuber and subependymal tumor. Ann Neurol 9: 174- 181, 1981
Bancel B, Belin MF, Meiniel A, et al: Contribution a l’etude de l’histogenese des gliomes sous ependymaires de la sclerose tubereuse de Bourneville. Ann Pathol 10: 109-116, 1990
Iwasaki Y, Yoshikawa H, Sasaki M, et al: Clinical and immunohistochemical studies of subependymal giant cell astrocytoma associated with tuberous sclerosis. Brain Dev 12: 478-481, 1990
Stefanssan K, Wollmann RL: Distribution of neuronal specific protein 14-3.2 in central nervous system lesions of tuberous sclerosis. Acta Neuropathol, Berl, 53: 113-117, 1981
Nakamura S, Tsubokawa T: Ultrastructure of subependymal giant cell astrocytoma associated with tuberous sclerosis. J Clin Electron Microscope 20: 5-6, 1987
Bonetti F, Chiodera PL, Pea M, et al: Transbronchial biopsy in lymphangiomyomatosis of the lung: HMB- 45 for diagnosis. Am J Surg Pathol 17:1092-1102, 1993
Gyure KA, Hart WR, Kennedy AW: Lymphangiomyomatosis of the uterus associated with tuberous sclerosis and malignant neoplasia of the female genital tract: a report of two cases. Int J Gynecol Pathol 14: 344-351, 1995
Pea M, Bonetti F, Zamboni G, et al: Melanocyte marker HMB- 45 is regularly expressed in angiomyolipoma of the kidney. Pathology 23: 185-188, 1991
Weeks DA, Chase DR, Malott RL, et al: HMB-45 staining in angiomyolipoma, cardiac rhabdomyoma, other mesenchymal processes and tuberous sclerosis associated brain lesions. Int J Surg Pathol 1:191-198, 1994
Al-Saleem T, Wessner LL, Scheithauer BW, et al: Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex. Cancer 83: 2208-2216, 1988
Kingsley DPE, Kendall BE, Fitz CR: Tuberous sclerosis: A clinico-radiological evaluation of 110 cases with particular reference to atypical presentation. Neuroradiology 28: 38-46, 1986
Boesel CP, Paulson GW, Kosnik EJ, Earle KM: Brain hamartomas and tumors associated with tuberous sclerosis. Neurosurgery 4: 410-417, 1979
Padmalatha C, Harsuff RC, Ganick D, Hafez GR: Glioblastoma multiforme with tuberous sclerosis. Arch Lab Med 105: 645-650, 1980
Brown JM: Tuberous sclerosis with malignant astrocytoma. Med J Austr 1:811-814, 1975.
Medhkour A, Traul D, Husain M: Neonatal subependymal giant cell astrocytoma. Ped Neurosurg 36: 271-274, 2002
Gyure KA, Prayson RA: Subependymal giant cell astrocytoma: A clinicopathologic study with HMB-45 and MIB-1 immunohistochemical analysis. Mod Pathol 10: 313-317, 1997
Bacchi CE, Bonetti F, Pea M, et al: HMB-45: a review. Appl Immunohistochem 4: 73-85, 1996
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 219
EP 224
PG 6
ER
PT J
AU Sharifzadeh, S
Owji, MS
Pezeshki, MA
Malek-Hoseini, Z
Kumar, VP
Ghayumi, MAS
Ghaderi, A
AF Sharifzadeh, Sedigheh
Owji, Mohammad Seyed
Pezeshki, Mohammad Abdul
Malek-Hoseini, Zahra
Kumar, Vijayananda Perikala
Ghayumi, Mohammad Ali Sied
Ghaderi, Abbas
TI Establishment and Characterization of a Human Large Cell Lung Cancer Cell Line with Neuroendocrine Differentiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cell line; lung cancer; large cell carcinoma; neuroendocrine differentiation
ID cell line; lung cancer; large cell carcinoma; neuroendocrine differentiation
AB Characterization of a human lung cancer cell line is reported. This cell line was established from a patient referred to Nemazi Hospital of Shiraz University of Medical Sciences with a diagnosis of poorly differentiated carcinoma. Sterile sample from peritoneal effusion was taken and immediately cultured in RPMI-1640 medium containing 20% FBS, at 37C with 5% CO2. This cell line has been in continuous culture for more than one year and has been named as Mehr-80. Several features of the cell line were investigated, including growth characteristics, electron microscopic features, cloning efficiency in soft agar, expression of various antigenic markers, chromosomal and DNA analysis. On the basis of morphological and immunohistochemical analysis of Mehr-80, it is possible to conclude that this cell line is characterized by features similar to those reported for large cell carcinoma with neuroendocrine differentiation (LCCND). This cell line will be a valuable in vitro tool for further studies on lung cancers.
C1 [Sharifzadeh, Sedigheh] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Owji, Mohammad Seyed] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Pezeshki, Mohammad Abdul] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Malek-Hoseini, Zahra] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Kumar, Vijayananda Perikala] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Ghayumi, Mohammad Ali Sied] Shiraz University of Medical Sciences, Department of Internal MedicineShiraz, Iran.
[Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Ghaderi, A (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM ghaderia@sums.ac.ir
CR Pisani P, Parkin DM, Bary F, Ferlay J: Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18- 29, 1999
Ferlay J, Bray F, Pisani P, Parkin DM: GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0 IARC Cancer Base No.5. IARC Press, Lyon 2001
Travis WD, Colby TV, Corrin B: Histological typing of lung and pleural tumors. 3rd ed., Berlin, Springer 1999
Iyoda A, Hiroshima K, Baba M, et al: Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors. Ann Thorac Surg 73: 1049-1054, 2002
Difilippantonio S, Chen Y, Pietas A, et al: Gene expression profiles in human non-small and small-cell lung cancers. Eur J Cancer 39: 1936-1947, 2003
Yamagata N, Shyr Y, Yanagisawa K, et al: A training-testing approach to the molecular classification of resected non-small cell lung cancer. Clin Cancer Res 9: 4695-4704, 2003
Lim EH, Aggarwal A, Agasthian T, et al: Feasibility of using low-volume tissue samples for gene expression profiling of advanced non-small cell lung cancers. Clin Cancer Res 9: 5980-5987, 2003
Bonner AE, Lemon WJ, Devereux TR, et al: Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinoma. Oncogene 3:1166-1176, 2004
Yesner R: Heterogeneity of so-called neuroendocrine lung tumors. Exp Mol Pathol 70: 179-182, 2001
Macikova I, Perzelova A, Mraz P, et al: Establishment, morphological, growth and cytoskeletal properties of 135-BCA carcinoma cell line derived from lung brain metastasis. Neoplasma 48: 479-482, 2001
Harada R, Uemura Y, Kobayashi M, et al: Establishment and characterization of a new lung cancer cell line, MI-4, producing high levels of granulocyte colony stimulating factor. Jpn J Cancer Res 93: 667-676, 2002
Kozaki K, Miyaishi O, Tsukamoto T, et al: Establishment and characterization of a human lung cancer cell line NCI-H460- LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation. Cancer Res 60:2535-2540, 2000
Sekio Y, Sato M, Usami N, et al: Establishment of a large cell lung cancer cell line, Y-ML-1B, producing granulocyte colony-stimulating factor. Cancer Genet Cytogenet 137: 33- 42, 2002
Shijubo N, Inoue Y, Hirasawa M, et al: Granulocyte colonystimulating factor-producing large cell undifferentiated carcinoma of the lung. Intern Med 3: 277-280, 1992
Suzuki A, Takahashi T, Okuno Y, et al: Analysis of abnormal expression of g-csf gene in a novel tumor cell line, KHC 287, elaborating G-CSF, IL-1 and IL-6 with co-amplification of cmyc and c-ki-ras. Int J Cancer 48: 428-433, 1991
Shibuya T: Establishment of a G-CSF and GM-CSF producing cell line from human large cell line from human large cell carcinoma of the lung. Eur J Haematol 43: 182-183, 1989
Visscher DW, Zabro RJ, Trojanowski JQ, et al: Neuroendocrine differentiation in poorly differentiated lung carcinoma: a light microscopic and immunohistologic study. Mod Pathol 3: 508- 512, 1990
Jiang SX, Kameya T, Shoji M, et al: Large cell neuroendocrine carcinoma of the lung: A histologic and immunohistochemical study of 22 cases. Am J Surg Pathol 22: 526-537, 1998
Upton MP, Hirohashi S, Tome Y, et al: Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung. Am J Surg Pathol 10: 560-567, 1986
Roberts HL, Komaki R, Allen P, et al: Prognostic significance of DNA content in stage I adenocarcinoma of the lung. Int J Radiat Oncol Biol Phys 41: 573-578, 1998
Yousem SA, Taylor SR: Typical and atypical carcinoid tumors of lung: a clinicopathologic and DNA analysis of 20 tumors. Mod Pathol 3: 502-507, 1990
Volm M, Mattern J, Sonka J, et al: DNA distribution in nonsmall- cell lung carcinomas and its relationship to clinical behavior. Cytometry 6: 348-356, 1985
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 225
EP 230
PG 6
ER
PT J
AU Dekel, Y
Rath-Wolfson, L
Rudniki, C
Koren, R
AF Dekel, Yoram
Rath-Wolfson, Lea
Rudniki, Carlos
Koren, Rumelia
TI Talc Inhalation is a Life-Threatening Condition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE talc inhalation; fibrosis; adult respiratory distress syndrome
ID talc inhalation; fibrosis; adult respiratory distress syndrome
AB A case of rapidly progressive disease and pulmonary hypertension due to chronic cosmetic talc inhalation is presented. Although an uncommon cause of pulmonary hypertension, talc, especially through intravenous administration, should be included in the etiology of parenchymal pulmonary hypertension. In our case talc inhalation was inadvertent, causing fulminant disease leading to the patient’s death. To our knowledge, this is the first case of inadvertent talc inhalation causing death in adult patient.
C1 [Dekel, Yoram] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Rath-Wolfson, Lea] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Rudniki, Carlos] Tel Aviv University, Sackler Faculty of Medicine, Ramat Aviv, 69978 Tel Aviv, Israel.
[Koren, Rumelia] Tel Aviv University, Sackler Faculty of Medicine, Ramat Aviv, 69978 Tel Aviv, Israel.
RP Koren, R (reprint author), Tel Aviv University, Sackler Faculty of Medicine, 69978 Tel Aviv, Israel.
EM rumelia@isdnmail.co.il
CR Abraham JL, Brambilla C: Particle size for differentiation between inhalation and injection pulmonary talcosis. Environ Res 21: 94-96, 1980
Arnett EN, Battle WE, Russo JV, et al: Intravenous injection of talccontaining drugs intended for oral use. A cause of pulmonary granulomatosis and pulmonary hypertension. Am J Med 60: 711-718, 1976
Avolio G, Galietti F, Oliaro A, et al: Talcosis as an occupational disease. Case histories. Minerva Med 80: 269-273, 1989
Bignon J, Brochard P: Pulmonary fibrosis and inorganic particles. Rev Fr Mal Respir 11: 371-382, 1983
Canessa PA, Torraca A, Lavecchia MA, et al: Primary acute pulmonary cavitation in asymptomatic sarcoidosis. Sarcoidosis 6: 158- 160, 1989
Cotton WH, Davidson PJ: Aspiration of baby powder. N Engl J Med 313: 1662, 1985
Crouch E, Churg A: Progressive massive fibrosis of the lung secondary to intravenous injection of talc. A pathologic and mineralogic analysis. Am J Clin Pathol 80: 520-526, 1983
Egan AJ, Tazelaar HD, Myers JL, et al: Munchausen syndrome presenting as pulmonary talcosis. Arch Pathol Lab Med 123: 736-738, 1999
Gibbs AE, Pooley FD, Griffiths DM, et al: Talc pneumoconiosis: a pathologic and mineralogic study. Hum Pathol 23:1344-1354, 1992
Gutermuth M, Schirg E, Steinbacher D, et al: Accidental aspiration of baby powder. Radiographic findings, preventive and therapeutic aspects. Intensivmed Prax 2: 83-92, 1980
Hollinger MA: Pulmonary toxicity of inhaled and intravenous talc. Toxicol Lett 52: 121-127, 1990
Honda Y, Beall C, Delzell E, et al: Mortality among workers at a talc mining and milling facility. Ann Occup Hyg 46: 575-585, 2002
Hopkins GB: Pulmonary angiothrombotic granulomatosis in drug offenders. JAMA 221: 909-911, 1972
Lamb D, Roberts G: Starch and talc emboli in drug addicts’ lungs. J Clin Pathol 25: 876-881, 1972
Lundquest DE, Young WK, Edland JF: Maternal death associated with intravenous methylphenidate, Ritalin, and pentazocine, Talwin, abuse. J Forensic Sci 32: 798-801, 1987
Magnan A, Ottomani A, Garbe L, et al: Respiratory failure in a HIV seropositive heroin addict female. Ann Fr Anesth Reanim 10: 74- 76, 1991
Motomatsu K, Adachi H, Uno T: Two infant deaths after inhaling baby powder. Chest 75: 448-450, 1979
Oubeid M, Bickel JT, Ingram EA, et al: Pulmonary talc granulomatosis in a cocaine sniffer. Chest 98: 237-239, 1990
Pairaudeau PW, Wilson RG, Hall MA, et al: Inhalation of baby powder: an unappreciated hazard. BMJ 302: 1200-1201, 1991
Pfenninger J, D’Apuzzo V: Powder aspiration in children. Report of two cases. Arch Dis Child 52: 157-159, 1977
Pickrell JA, Snipes MB, Benson JM, et al: Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc. Environ Res 49: 233-245, 1989
Reyes de la Rocha S, Brown MA: Normal pulmonary function after baby powder inhalation causing adult respiratory distress syndrome. Pediatr Emerg Care 5: 43-48, 1989
Scancarello G, Romeo R, Sartorelli E: Respiratory disease as a result of talc inhalation. J Occup Environ Med 38: 610-614, 1996
Steele AA: Suicidal death by aspiration of talcum powder. Am J Forensic Med Pathol 11: 316-318, 1990
Wehner AP: Biological effects of cosmetic talc. Food Chem Toxicol 32: 1173-1184, 1994
Zazenski R, Ashton WH, Briggs D, et al: Talc: occurrence, characterization, and consumer applications. Regul Toxicol Pharmacol 21: 218-229, 1995
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 231
EP 233
PG 3
ER
PT J
AU Culhaci, N
Meteoglu, I
Kacar, F
Ozbas, S
AF Culhaci, Nil
Meteoglu, Ibrahim
Kacar, Furuzan
Ozbas, Serdar
TI Abscess of the Spleen
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE abscess; spleen; immunosuppression
ID abscess; spleen; immunosuppression
AB Abscess of the spleen is a very rare lesion. In this study, 4 cases of splenic abscess are presented and discussed along with the literature. The cases were between 16 and 55 years-old and two of them had hematologic malignancy. All of them had been operated on because of acute abdomen, and in two cases splenic rupture was present. Only in one of the cases was salmonellosis detected by microbiological methods. By histological examination, expansion and congestion in splenic sinusoids, and foci of abscess including wide areas of necrosis and inflammatory infiltration by neutrophils were seen in all cases. The most frequent cause of splenic abscess is septic embolism arising from bacterial endocarditis. There are also a few splenic abscess cases seen with malignancies. While splenic abscess is seen rarely, it has a high rate of mortality when it is diagnosed late.
C1 [Culhaci, Nil] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Meteoglu, Ibrahim] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Kacar, Furuzan] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Ozbas, Serdar] Adnan Menderes University Medical School, Department of SurgeryAydin, Turkey.
RP Culhaci, N (reprint author), Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
EM nculhaci@hotmail.com
CR Spleen. In: Ackerman’s Surgical Pathology., Ed: Rosai J), Mosby-Year Book, 8th ed., St. Louis, MO, 1996, pp. 1777-1778
Changchien CS, Tsai TL, Hu TH, et al: Sonographic patterns of splenic abscess: an analysis of 34 proven cases. Abdom Imaging 27: 739-745, 2002.
Smyrniotis V, Kehagias D, Voros D, et al: Splenic abscess. An old disease with new interest. Dig Surg 17: 354-357, 2000
Ramakrishnan MR, Sarathy TKP, Balu M: Percutaneous drainage of splenic abscess: case report and review of literature. Pediatrics 79: 1029-1030, 1987
Aessopos A, Politou M, Farmakis D, et al: Staphylococcus aureus abscess of the spleen in a beta-thalassemia patient. Scand J Infect Dis 34: 466-480, 2002
Colmenero JD, Queipo-Ortuno MI, Reguera JM, et al: Chronic hepatosplenic abscess in brucellosis. Clinico-therapeutic features and molecular diagnostic approach. Diagn Microbiol Infect Dis 42:159-167, 2002
Yayly G, Yºler M, Oyar O: Medically treated splenic abscess due to Brucella melitensis. Scand J Infect Dis 34: 133-135, 2001
Shedda S, Campbell I, Skinner I. Clostridium difficile splenic abscess. Aust NZ J Surg 70: 147-148, 2000
Wald BR, Ortega JA, Ross L, et al: Candidal splenic abscess complicating acute leukemia of childhood treated by splenectomy. Pediatrics 67:296-99, 1981
Bessho H, Ichihara I, Takii M: A case of splenic abscess due to Chlamydia pneumoniae. Diagn Microbiol Infect Dis 39: 261- 264, 2001
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 234
EP 236
PG 3
ER
PT J
AU Vargas Gonzalez, R
San Martin-Brieke, W
Gil-Orduna, C
Lara-Hernandez, F
AF Vargas Gonzalez, Roberto
San Martin-Brieke, Walter
Gil-Orduna, Claudia
Lara-Hernandez, Fabiola
TI Desmoplastic Fibroma-Like Tumor of Maxillofacial Region Associated with Tuberous Sclerosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE desmoplastic fibroma; desmoid tumor; bone tumor; tuberous sclerosis
ID desmoplastic fibroma; desmoid tumor; bone tumor; tuberous sclerosis
AB Desmoplastic fibroma is a rare primary tumor of bone that histologically and biologically mimics the extra-abdominal desmoid tumor of soft tissue. It usually presents in patients during the first three decades of life and often involves the mandible or long bones of the skeleton. Its clinical behavior is characterized by a locally aggressive, infiltrating, and destructing course, often with invasion of surrounding tissues but without metastasis. We present herein the clinicopathological features of a desmoplastic fibroma-like tumor involving the left maxillofacial region in a 14-year-old Hispanic boy with tuberous sclerosis.
C1 [Vargas Gonzalez, Roberto] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla-Atlixco, 72190 Puebla, Mexico.
[San Martin-Brieke, Walter] Hospital Para el Nino Poblano, Department of Maxillofacial SurgeryPuebla, Mexico.
[Gil-Orduna, Claudia] Hospital Para el Nino Poblano, and Facultad de Estomatologia B.U.A.P., Department of EstomatologyPuebla, Mexico.
[Lara-Hernandez, Fabiola] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla-Atlixco, 72190 Puebla, Mexico.
RP Vargas Gonzalez, R (reprint author), Hospital Para el Nino Poblano, Department of Pathology, 72190 Puebla, Mexico.
EM soncoy@msn.com
CR Miyamoto Y, Satomura K, Rikimaru K, Hayashi Y: Desmoplastic fibroma of the mandible associated with tuberous sclerosis. J Oral Pathol Med 24: 93-96, 1995
Damm DD, Tomich CE, White DK, et al: Intraosseous fibrous lesions of the jaws: a manifestation of tuberous sclerosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87: 334-340, 1999
Jaffe HL: Tumors and Tumorous Conditions of the Bones and Joints. Lea & Febiger, Philadelphia, PA, 1958, pp 298–303
Inwards CY, Unni KK, Beabout JW, Sim FH: Desmoplastic fibroma of bone. Cancer 68: 1978–1983, 1991
Salzer Kuntschik M: Desmoplastishes Fibrom. In: Witt AN, Rettig H, Schlegel KF, Hackenbroch M, Hupfauer W, eds. Orthopadie in Praxis und Klinik, Band III: Allgemeine Orthopadie, Teil 2: Tumoren und tumorahnliche Erkrankungen, 2nd ed. Stuttgart, Germany: Georg Thieme Verlag 1: 258–265, 1984
Dahlin DC, Unni KK: Bone Tumors. 4th ed. Thomas, Springfield, IL, 1986, pp 375–378
Bohm P, Krober S, Greschniok A. et al: Desmoplastic fibroma of the bone: a report of two patients, review of the literature, and therapeutic implications. Cancer 78: 1011–1023, 1996
Crim JR, Gold RH, Mirra JM, et al: Desmoplastic fibroma of bone: radiographic analysis. Radiology 172: 827-832, 1989
Young JWR, Aisner SC, Levine AM, et al: Computed tomography of desmoid tumors of bone: desmoplastic fibroma. Skeletal Radiol 17: 333–337, 1998
Yeung RS: Multiple roles of the tuberous sclerosis complex genes. Genes Chromosomes Cancer 38: 368-375, 2003
Lygidakis NA, Lindenbaum RH: Oral fibromatosis in tuberous sclerosis. Oral Surg Oral Med Oral Pathol 68: 725-728, 1989
Scully C: Orofacial manifestations in tuberous sclerosis. Oral Surg Oral Med Oral Pathol 44:706-716, 1977
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 237
EP 239
PG 3
ER
PT J
AU Bolat, F
Kayaselcuk, F
Erkan, NA
Cagici, AC
Bal, N
Tuncer, I
AF Bolat, Filiz
Kayaselcuk, Fazilet
Erkan, Nabi Alper
Cagici, Alper Can
Bal, Nebil
Tuncer, Ilhan
TI Epidermoid Carcinoma Arising in Warthin’s Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Epidermoid carcinoma; Warthin’s tumor
ID Epidermoid carcinoma; Warthin’s tumor
AB Warthin’s tumor is a well-defined salivary gland neoplasm consisting of benign epithelial and lymphoid components. However, malignant transformation is extremely rare and the differential diagnosis of metastasis from an epidermoid carcinoma in Warthin’s tumor is important. We present a case with epidermoid carcinoma arising in Warthin’s tumor of parotid gland in a 48-year-old woman, and differential diagnosis is discussed.
C1 [Bolat, Filiz] Baskent University, Department of Pathology, Adana Hastanesi, Yure?ir, 01250 Adana, Turkey.
[Kayaselcuk, Fazilet] Baskent University, Department of Pathology, Adana Hastanesi, Yure?ir, 01250 Adana, Turkey.
[Erkan, Nabi Alper] Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Department of Ear-Throat-NoseAdana, Turkey.
[Cagici, Alper Can] Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Department of Ear-Throat-NoseAdana, Turkey.
[Bal, Nebil] Baskent University, Department of Pathology, Adana Hastanesi, Yure?ir, 01250 Adana, Turkey.
[Tuncer, Ilhan] Baskent University, Department of Pathology, Adana Hastanesi, Yure?ir, 01250 Adana, Turkey.
RP Bolat, F (reprint author), Baskent University, Department of Pathology, 01250 Adana, Turkey.
EM drfilizbolat@yahoo.com
CR Huvos AG, Paulino AFG: Salivary Glands. In: Diagnostic Surgical Pathology., Eds: Stenberg SS), 3rd edition, Lippincott Williams&Wilkins, Philedelphia, 1999, pp 861-862
Gunduz M, Yamanaka N, Hotomi M, et al: Squamous cell carcinoma arising in a Warthin’s tumor. Auris Nasus Larynx 26:355- 360, 1999
Skalova A, Michal M, Nathansky Z: Epidermoid carcinoma arising in Warthin’s tumour: a case study. J Oral Pathol Med 23:330- 333, 1994
Morrison GAJ, Shaw HJ: Squamous carcinoma arising within a Warthin’s tumor of the parotid gland. J Laryngol Otol 102:1189- 1191, 1988
Damjanov I, Sneff EM, Delerme AN: Squamous cell carcinoma arising in Warthin’s tumor of the parotid gland. A light, electron microscopic, and immunohistochemical study. Oral Surg Oral Med Oral Pathol 55:286-290, 1983
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 240
EP 242
PG 3
ER
PT J
AU Swiatoniowski, G
Mazur, G
Halon, A
Rozumek, G
Dabrowska, M
Zawisza, R
Prudlak, E
AF Swiatoniowski, Grzegorz
Mazur, Grzegorz
Halon, Agnieszka
Rozumek, Grzegorz
Dabrowska, Maria
Zawisza, Radoslaw
Prudlak, Edmun
TI Malignant Melanoma with Gall Bladder Metastasis as a Second Neoplasm in the Course of Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE prostate cancer; malignant melanoma; hormone therapy; second neoplasm
ID prostate cancer; malignant melanoma; hormone therapy; second neoplasm
AB Malignant melanoma is a neoplasm with an often unpredictable course and metastases potentially affecting all organs of the human body. Metastases into the gall bladder are rare. The role of hormonal background in the development and progression of malignant melanoma has not been established. The authors present a case of a 63-year-old man who had initially undergone long-term hormone therapy for the treatment of prostate cancer, and later presented with melanoma metastatic to the gall bladder.
C1 [Swiatoniowski, Grzegorz] 4th Academic Military Hospital, Department of Internal MedicineWroclaw, Poland.
[Mazur, Grzegorz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 4, 50-367 Wroclaw, Poland.
[Halon, Agnieszka] Wroclaw Medical University, Department of PathologyWroclaw, Poland.
[Rozumek, Grzegorz] 4th Academic Military Hospital, Department of Internal MedicineWroclaw, Poland.
[Dabrowska, Maria] 4th Academic Military Hospital, Department of Internal MedicineWroclaw, Poland.
[Zawisza, Radoslaw] 4th Academic Military Hospital, Department of SurgeryWroclaw, Poland.
[Prudlak, Edmun] 4th Academic Military Hospital, Department of Internal MedicineWroclaw, Poland.
RP Mazur, G (reprint author), Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 50-367 Wroclaw, Poland.
EM grzegmaz@hemat.am.wroc.pl
CR Feskanich D, Hunter DJ, Willett WC, et al: Oral contraceptive use and risk of melanoma in premenopausal women. Br J Cancer 81: 918-923, 1999
Grin CM, Driscoll MS, Grant-Kels JM: The relationship of pregnancy, hormones, and melanoma. Semin Cutan Med Surg 17: 167-171, 1998
Grostern RJ, Slusker-Shternfeld I, Bacus SS, et al: Absence of type I estrogen receptors in choroidal melanoma: analysis of Collaborative Ocular Melanoma Study, COMS, eyes. Am J Ophthalmol 131: 788-791, 2001
Heath DI, Womack C: Primary malignant melanoma of the gall bladder. J Clin Pathol 41: 1073-1077, 1988
Higgins CM, Strutton GM: Malignant melanoma of the gall bladder – does primary melanoma exist? Pathology 27: 312- 314, 1995
Jones JA, Albright KD, Christen RD, et al: Synergy between tamoxifen and cisplatin in human melanoma cells is dependent on the presence of antiestrogen-binding sites. Cancer Res 57: 2657-2660, 1997
Kanter-Lewensohn L, Girnita L, Girnita A, et al: Tamoxifeninduced cell death in malignant melanoma Wells: possible involvement of the insulin-like growth factor 1, IGF-1, pathway. Mol Cell Endocrinol 165: 131-137, 2000
Kohler U, Jacobi T, Sebastian G, Nagel M: Laparoscopic cholecystectomy in isolated gallbladder metastasis of malignant melanoma. Chirurg 71: 1517-1520, 2000
Lama G, Angelucci C, Bruzzese N, et al: Sensitivity of human melanoma cells to oestrogens, tamoxifen and quercetin: is there any relationship with type I and II estrogen binding site expression? Melanoma Res 8: 313-322, 1999
Langley RG, Bailey EM, Sober AJ: Acute cholecystitis from metastatic melanoma to the gall-bladder in a patient with a low-risk melanoma. Br J Dermatol 136: 279-282, 1997
Miller JG, Gee J, Price A, et al: Investigation of estrogen receptors, sex steroids and soluble adhesion molecules in the progression of malignant melanoma. Melanoma Res 7: 197-208, 1997
Ostick DG, Haqqani MT: Obstructive cholecystitis due to metastatic melanoma. Postgrad Med J 52: 710-712, 1976
Richardson B, Price A, Wagner M, et al: Investigation of female survival benefit in metastatic melanoma. Br J Cancer 80: 2025-2033, 1999
Rusthoven JJ: The evidence for tamoxifen and chemotherapy as treatment for metastatic melanoma. Eur J Cancer 34, Suppl 3): S31-S36, 1998
Seelig MH, Schonleben K: Laparoscopic cholecystectomy for a metastasis of a malignant melanoma in the gallbladder. Z Gastroenterol 35: 673-675, 1997
Toma S, Ugolini D, Palumbo R: Tamoxifen in the treatment of metastatic malignant melanoma: still a controversy? Int J Oncol 15: 321-337, 1999
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2004
VL 10
IS 4
BP 243
EP 245
PG 3
ER
PT J
AU Kopper, L
Timar, J
AF Kopper, Laszlo
Timar, Jozsef
TI Genomics of Lung Cancer may Change Diagnosis, Prognosis and Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lung cancer; genomics
ID lung cancer; genomics
AB Despite significant improvements in tumor management in general, the prognosis of lung cancer patients remains dismal. It is a hope that our increasing knowledge in molecular aspects of tumor development, growth and progression will open new targets for therapeutic interventions. In this review we discuss some of the more recent results of this field. This includes the susceptibility factors, an association between genetic changes in EGFR pathway and tyrosine kinase inhibitors, the role of gene hypermethylation and genetic profiling, as well as different molecular aspects of tumor progression. Available data all support that lung cancer is a group of diseases with not only distinct histological but with similarly different genetic characters. Accordingly, the diagnosis, prognosis and therapy must accommodate this heterogeneity.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor ProgressionBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Schwartz AG: Genetic predisposition to lung cancer. Chest 125: 86S-89S, 2004
Olak J, Colson Y: Gender differences in lung cancer: Have we really come a long way, baby? J Thorac Cardiovasc Surg 128: 346-351, 2004
Minna JD, Roth JA, Gazdar AF: Focus on lung cancer. Cancer Cell 1: 49-52, 2002
Balsara BR, Testa JR: Chromosomal imbalances in human lung cancer. Oncogene 21: 6877-6883, 2002
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 5
EP 10
PG 6
ER
PT J
AU Orosz, Zs
Tornoczky, T
Sapi, Z
AF Orosz, Zsolt
Tornoczky, Tamas
Sapi, Zoltan
TI Gastrointestinal Stromal Tumors: A Clinicopathologic and Immunohistochemical Study of 136 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-kit; CD117; gastrointestinal stromal tumor (GIST); inflammatory fibroid polyp; leiomyoma; leiomyosarcoma; schwannoma
ID c-kit; CD117; gastrointestinal stromal tumor (GIST); inflammatory fibroid polyp; leiomyoma; leiomyosarcoma; schwannoma
AB The clinicopathologic features of 136 gastrointestinal stromal tumors were analyzed. The tumors occurred in 60 women and 76 men, ranging in age from 19 to 88 years (median 59 years, mean 59.2 years). Sixty-one cases arose from stomach, 38 from small intestine and 11 from colon or rectum. Abdominal cavity was indicated as tumor site in 10 cases, but the extragastrointestinal origin using strict criteria was not proved. Four locally recurrent cases and 12 metastatic samples were also included. The primary and recurrent tumors ranged in size from 0.5 to 30 cm (mean 8.3 cm). The large number of high-grade cases (85 of 112 classifiable) is alarming and emphasize the importance of oncology care. Histologically, ninety-two cases were classified as spindle cell while 11 as epithelioid GIST. Mixed cellularity was seen in 33 cases. Skeinoid fibers were present in 14 and coagulation necrosis in 40 primary cases. Ulceration observed by microscopic examination was common (36 of 110 cases, 32.7%), explaining the clinically frequently observed gastrointestinal bleeding. Unusual histological features such as stromal hyalinization and nuclear palisading were present in 30 and 27 cases, respectively. Immunohistochemical CD117 (c-kit) positivity was documented in 133 cases. Three cases with CD117 negative results were included, because their morphology was most consistent with GIST and immunohistochemical reactions excluded the possibility of other neoplasms. CD34 positivity was seen in 70%, alpha-smooth muscle actin positivity in 39.6% of examined cases. Only one case showed desmin reactivity and seven had S100 positive tumor cells. For h-caldesmon 39 cases proved to be positive (60.9% of the tested cases).
C1 [Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Tornoczky, Tamas] University of Pecs, Department of PathologyPecs, Hungary.
[Sapi, Zoltan] St John's Hospital, Department of PathologyBudapest, Hungary.
RP Orosz, Zs (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
EM zso@oncol.hu
CR Ceballos KM, Nielsen GP, Selig MK, O’Connell JX: Is anti-hcaldesmon useful for distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study. Am J Clin Pathol 114: 746-753, 2000
Corless CL, Fletcher JA, Heinrich MC: Biology of gastrointestinal stromal tumors. J Clin Oncol 22: 3813-3825, 2004
Daum O, Hes O, Vanecek T, et al: Vanek’s tumor, inflammatory fibroid polyp). Report of 18 cases and comparison with three cases of original Vanek’s series. Mod Pathol 16:366-375, 2003
DeMatteo RP, Lewis JJ, Leung D, et al: Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231:51-58, 2000
de Silva CM, Reid R: Gastrointestinal stromal tumors, GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with Imatinib. Pathol Oncol Res 9:13- 19, 2003
Eckhardt S, Papai Zs, Bodoky Gy, et al: Az imatinib kezeles hatasa gastrointestinalis stroma eredetu daganatokban [Effect of imatinib treatment of gastrointestinal stromal tumors] Orv Hetil 144:2207-2212, 2003
Emile JF, Theou N, Tabone S, et al: Clinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors. Clin Gastroenterol Hepatol 2:597-605, 2004
Fletcher CDM, Berman JJ, Corless C, et al: Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 33: 459-465, 2002
Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T: Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer 6: 39-48, 2003
Greenson JK: Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol 16: 366-375, 2003
Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S: Gastrointestinal stromal tumor: consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol 33: 669-676, 2002
Hirota S, Isozaki K, Moriyama Y, et al: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279: 577–580, 1998
Hjermstad BM, Sobin LH, Helwig EB: Stromal tumors of the gastrointestinal tract: myogenic or neurogenic? Am J Surg Pathol 11:383-386, 1987
Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 344:1052-1056, 2001
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Kwon MS, Lee SS, Ahn GH: Schwannomas of the gastrointestinal tract: clinicopathological features of 12 cases including a case of esophageal tumor compared with those of gastrointestinal stromal tumors and leiomyomas of the gastrointestinal tract. Pathol Res Pract 198: 605-613, 2002
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Miettinen M, Kopczynski J, Makhlouf HR, et al: Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 27:625-641, 2003
Miettinen M, Lasota J: Gastrointestinal stromal tumors – definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 438:1-12, 2001
Miettinen M, Shekitka KM, Sobin LH: Schwannomas in the colon and rectum: a clinicopathologic and immunohistochemical study of 20 cases. Am J Surg Pathol 25: 846-855, 2001
Miettinen M, Sobin LH, Sarlomo-Rikala M: Immunohistochemical spectrum of GISTs at different sites a their differential diagnosis with a reference to CD117, KIT). Mod Pathol 13: 1134-1142, 2000
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Stout AP: Bizarre smooth muscle tumors of the stomach. Cancer 15:400-409, 1962
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Yantiss RK, Spiro IJ, Compton CC, Rosenberg AE: Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis. Am J Surg Pathol 24:947-957, 2000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 11
EP 21
PG 11
ER
PT J
AU Demokan, S
Demir, D
Suoglu, Y
Kiyak, E
Akar, U
Dalay, N
AF Demokan, Semra
Demir, Deniz
Suoglu, Yusufhan
Kiyak, Erkan
Akar, Ugur
Dalay, Nejat
TI Polymorphisms of the XRCC1 DNA Repair Gene in Head and Neck Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE polymorphism; XRCC1; head and neck cancer
ID polymorphism; XRCC1; head and neck cancer
AB Inherited polymorphisms in the genes controlling the cell cycle or functioning in the DNA repair mechanisms may impair their function and contribute to genetic susceptibility. Abnormalities in the DNA repair have been reported in head and neck cancer. The XRCC1 gene functions in singlestrand break and base excision repair processes. In this study, two polymorphisms of the XRCC1 gene, Arg194Trp and Arg399Gln were investigated in 95 patients with head and neck carcinoma. The polymorphic regions were amplified by PCR followed by digestion with methylation-specific restriction enzymes, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and association with cancer risk or clinical parameters was investigated. No association was observed between the genotypes and head and neck cancer for either polymorphism. Distribution of the alleles did not significantly differ between the patients and the control group. A significant association was only found for the Trp194 allele among the smoking individuals. Our data indicate that the Arg194Trp and Arg399Gln polymorphisms do not confer a significant risk for head and neck carcinogenesis.
C1 [Demokan, Semra] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
[Demir, Deniz] Istanbul Medical Faculty, Istanbul University, Department of OtolaryngologyIstanbul, Turkey.
[Suoglu, Yusufhan] Istanbul Medical Faculty, Istanbul University, Department of OtolaryngologyIstanbul, Turkey.
[Kiyak, Erkan] Istanbul Medical Faculty, Istanbul University, Department of OtolaryngologyIstanbul, Turkey.
[Akar, Ugur] Istanbul Medical Faculty, Istanbul University, Department of Medical BiologyIstanbul, Turkey.
[Dalay, Nejat] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
RP Dalay, N (reprint author), Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34390 Istanbul, Turkey.
EM ndalay@yahoo.com
CR Abdel-Rahman SZ, Soliman AS, Bondy ML, et al: Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt. Cancer Lett 159: 79-86, 2000
Bohr VA: DNA repair fine structure and its relations to genomic instability. Carcinogenesis 16: 2885-2892, 1995
Butkiewicz D, Rusin M, Enewold L, et al:Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22: 593-597, 2001
Caldecott KW, Aoufouchi S, Johnson P, Shall S: XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly, ADPribose, polymerase, and DNA ligase III is a novel molecular ‘nicksensor’ in vitro. Nucleic Acids Res 24: 4387-4394, 1996
Cappelli E, Taylor R, Cevasco M, et al: Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. J Biol Chem 272: 23970-23975, 1997
Crowe DL: Molecular pathology of head and neck cancer. Histol Histopathol 17: 909-914, 2002
David-Beabes GL, London SJ:Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 34: 333-339, 2001
Divine KK, Gilliland FD, Crowell RE, et al:The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat Res 461: 273-278, 2001
Duell EJ, Millikan RC, Pittman GS, et al: Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev 10: 217-222, 2001
Goode EL, Ulrich CM, Potter JD:Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11: 1513-1530, 2002
Hu JJ, Mohrenweiser HW, Bell DA, et al: Symposium Overview: Genetic polymorphisms in DNA repair and cancer risk. Toxicol Appl Pharmacol 185: 64-73, 2002
Kubota Y, Nash RA, Klungland A, et al: Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J 15: 6662-6670, 1996
Lee SG, Kim B, Choi J, et al:Genetic polymorphisms of XRCC1 and risk of gastric cancer. Cancer Lett 187: 53-60, 2002
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Misra RR, Ratnasinghe D, Tangrea JA, et al: Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett 191:171-178, 2003
Nelson HH, Kelsey KT, Mott LA, Karagas MR: The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. Cancer Res 62:152-155, 2002
Olshan AF, Watson MA, Weissler MC, Bell DA:XRCC1 polymorphisms and head and neck cancer. Cancer Lett 178: 181-186, 2002
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Ratnasinghe D, Yao SX, Tangrea JA, et al:Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk. Cancer Epidemiol Biomarkers Prev 10:119-123, 2001
Scully C, Field JK, Tanzawa H: Genetic aberrations in oral or head and neck squamous cell carcinoma, SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol 36: 256-263, 2000
Scully C, Field JK, Tanzawa H: Genetic aberrations in oral or head and neck squamous cell carcinoma: 2. Chromosomal aberrations. Oral Oncol 36: 311-327, 2000
Shen MR, Jones IM, Mohrenweiser H: Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58: 604–608, 1998
Shen H, Xu Y, Qian Y, et al: Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. Int J Cancer 88:601-606, 2000
Shu XO, Cai Q, Gao YT, et al: A population based case control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12: 1462-1467, 2003
Stern MC, Umbach DM, van Gils CH, et al: DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. Cancer Epidemiol Biomarkers Prev 10:125-131, 2001
Sturgis EM, Castillo EJ, Li L, et al: Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. Carcinogenesis 20: 2125-2129, 1999
Sturgis EM, Wei Q:Genetic susceptibility-molecular epidemiology of head and neck cancer. Curr Opin Oncol 14: 310-317, 2002
Taningher M, Malacarne D, Izzotti A, et al: Drug metabolism polymorphisms as modulators of cancer susceptibility. Mutat Res 436: 227–261, 1999
Xing D, QI J, Miao X, et al:Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Int J Cancer 100: 600-605, 2002
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 22
EP 25
PG 4
ER
PT J
AU Sobel, G
Szabo, I
Paska, Cs
Kiss, A
Kovalszky, I
Kadar, A
Paulin, F
Schaff, Zs
AF Sobel, Gabor
Szabo, Istvan
Paska, Csilla
Kiss, Andras
Kovalszky, Ilona
Kadar, Anna
Paulin, Ferenc
Schaff, Zsuzsa
TI Changes of Cell Adhesion and Extracellular Matrix (ECM) Components in Cervical Intraepithelial Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE occludin; claudin; cervical intraepithelial neoplasia; syndecan-1; carcinogenesis
ID occludin; claudin; cervical intraepithelial neoplasia; syndecan-1; carcinogenesis
AB Cell-cell and cell-extracellular matrix interaction is crucial in tumor progression. Tight junction (TJ) proteins as occludin and claudins (CLDNs) play important role in this process together with several extracellular matrix components, as syndecan. Our previous work suggested significant changes in the expression of claudins even in the early stages of cervical carcinogenesis. The aim of our present work was to study the expression of occludin and syndecan-1, as compared to CLDNs, in early phases of cervical carcinogenesis. Paraffin sections of 50 samples were studied by immunohistochemistry, including cervical intraepithelial neoplasias (CINI-II-III), in situ carcinomas (CIS) and normal cervical samples. Occludin and CLDN-2 were found colocalized in the basal layer, while syndecan-1 and CLDN-1, -4 and -7 were coexpressed in the parabasal and intermedier layers in normal epithelia. Intensity of occludin staining decreased in CIN/CIS lesions, although it was more extended towards the upper epithelial layers with inverse relation with grades, as seen in the case of CLDN-2 expression. CLDN-1, -2, -4 and -7 were detected in the entire epithelium in CIN, showing decrease in CIS. The progression of CIN was associated with reduced syndecan-1 expression, in contrast to CLDN-1, -4 and -7 which increased toward CIS. The obtained data suggest that significant changes occur in the composition of cell adhesion complexes even in early stages of cervical carcinogenesis. The pattern of expression is characteristic for the alteration, the changes in the different components, however, are not parallel with each other.
C1 [Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Szabo, Istvan] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Paska, Csilla] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kadar, Anna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Paulin, Ferenc] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
CR Acharya P, Beckel J, Ruiz WG, et al: Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium. Am J Physiol Renal Physiol 287: F305-F318, 2004
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 26
EP 31
PG 6
ER
PT J
AU Bircan, S
Ensari, A
Ozturk, S
Erdogan, N
Dundar, I
Ortac, F
AF Bircan, Sema
Ensari, Arzu
Ozturk, Sibel
Erdogan, Nural
Dundar, Ilkkan
Ortac, Firat
TI Immunohistochemical Analysis of c-Myc, c-Jun and Estrogen Receptor in Normal, Hyperplastic and Neoplastic Endometrium
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE human endometrium; estrogen receptor; c-myc; c-jun
ID human endometrium; estrogen receptor; c-myc; c-jun
AB To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.
C1 [Bircan, Sema] Ankara University, School of Medicine, Department of Pathology, Suleyman Demirel Universitesi, Tip Fakultesi, Patoloji Anabilim Dali, IspartaAnkara, Turkey.
[Ensari, Arzu] Ankara University, School of Medicine, Department of Pathology, Suleyman Demirel Universitesi, Tip Fakultesi, Patoloji Anabilim Dali, IspartaAnkara, Turkey.
[Ozturk, Sibel] Ankara University, School of Medicine, Department of Pathology, Suleyman Demirel Universitesi, Tip Fakultesi, Patoloji Anabilim Dali, IspartaAnkara, Turkey.
[Erdogan, Nural] Ankara University, School of Medicine, Department of Pathology, Suleyman Demirel Universitesi, Tip Fakultesi, Patoloji Anabilim Dali, IspartaAnkara, Turkey.
[Dundar, Ilkkan] School of Medicine, University of Ankara, Department of Gynecological OncologyAnkara, Turkey.
[Ortac, Firat] School of Medicine, University of Ankara, Department of Gynecological OncologyAnkara, Turkey.
RP Bircan, S (reprint author), Ankara University, School of Medicine, Department of Pathology, Ankara, Turkey.
EM bircans2000@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 32
EP 39
PG 8
ER
PT J
AU Brnic, Z
Gasparov, S
Lozo, VP
Anic, P
Patrlj, L
Ramljak, V
AF Brnic, Zoran
Gasparov, Slavko
Lozo, Vladislav Petar
Anic, Petar
Patrlj, Leonardo
Ramljak, Vesna
TI Is Quadrant Biopsy Sufficient in Men Likely to Have Advanced Prostate Cancer? Comparison with Extended Biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostatic neoplasms; needle biopsy
ID prostatic neoplasms; needle biopsy
AB We hypothesized that quadrant prostate biopsy (QPB) provides sufficient first-line pathological evaluation of patients with presumed advanced prostate cancer (PC). The aim of this study was to investigate whether the reduction of core number in first-line PB from 6-12 to 4 in patients with presumed advanced PC leads to loss of clinically relevant information. We retrospectively studied 113 men that underwent PB, classified in two groups: ''H” (high) and ''L” (low likelihood of having advanced PC), according to PSA, digital rectal and transrectal ultrasound findings. Pathological results of 6-12-core PB and QPB were retrospectively compared for the presence of malignancy, percentage of positive cores, Gleason score (GS), and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN). PC detection rate was not impaired in group H but dropped significantly in group L, and the percentage of positive cores was not significantly changed in group H (p=0.39), but decreased in group L (p=0.04), due to sampling scheme reduction. No HGPIN was missed with QPB in group H, while 2 HGPINs were missed in group L. No significant change in GS in either group was observed (p=0.12, p=0.13) due to reduction to QPB. We conclude that in patients with presumed advanced PC, reduction of the number of cores in PB may be an acceptable diagnostic strategy, but further studies are needed to analyze the impact of PB scheme reduction on other relevant pathological information obtained from PB.
C1 [Brnic, Zoran] University Hospital Merkur, Department of Diagnostic and Interventional Radiology, Zajeeva 19, 10000 Zagreb, Croatia.
[Gasparov, Slavko] “Merkur” University Hospital, Department of Clinical Pathology and CytologyZagreb, Croatia.
[Lozo, Vladislav Petar] Poliklinika Lozo, Department of UltrasoundZadar, Croatia.
[Anic, Petar] University Hospital Merkur, Department of Diagnostic and Interventional Radiology, Zajeeva 19, 10000 Zagreb, Croatia.
[Patrlj, Leonardo] University Hospital Merkur, Department of Diagnostic and Interventional Radiology, Zajeeva 19, 10000 Zagreb, Croatia.
[Ramljak, Vesna] University Hospital for TumorsZagreb, Croatia.
RP Brnic, Z (reprint author), University Hospital Merkur, Department of Diagnostic and Interventional Radiology, 10000 Zagreb, Croatia.
EM zoran.brnic@zg.t-com.hr
CR Aus G, Ahlgren G, Hugosson J, et al: Diagnosis of prostate cancer: optimal number of prostate biopsies related to serum prostate-specific antigen and findings on digital rectal examination. Scand J Urol Nephrol 31: 541-544, 1997
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Ravery V, Goldblatt L, Royer B, et al: Extensive biopsy protocol improves the detection rates of prostate cancer. J Urol 164: 393-396, 2000
Ruijter E, van Leenders G, Miller G, et al: Errors in histologic grading by prostatic needle biopsy specimens: frequency and predisposing factors. J Pathol 192: 229-233, 2000
San Francisco IF, DeWolf WC, Rosen S, et al:Extended prostate needle biopsy improves concordance of Gleason grading between prostate needle biopsy and radical prostatectomy. J Urol 169: 136-140, 2003
Soloway MC, Obek C: Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol 163: 172-173, 2000
Szabo J, Hegedus G, Bartok K, et al: Improving diagnostic accuracy of prostate carcinoma by systematic random mapbiopsy. Pathol Oncol Res 6: 111-113, 2000
Tigrani VS, Bhargava V, Shinohara K, Presti JC Jr: Number of positive systematic sextant biopsies predicts surgical margin status at radical prostatectomy. Urology 54: 689-693, 1999
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Yamamoto T, Ito K, Ohi M, et al:Diagnostic significance of digital rectal examination and transrectal ultrasonography in men with prostate-specific antigen levels of 4 ng/mL or less. Urology 58: 994-998, 2001
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 40
EP 44
PG 5
ER
PT J
AU Hadar, T
Shvero, J
Yaniv, E
Ram, E
Shvili, I
Koren, R
AF Hadar, Tuvia
Shvero, Jacob
Yaniv, Eitan
Ram, Eduard
Shvili, Itzhak
Koren, Rumelia
TI Expression of p53, Ki-67 and Bcl-2 in Parathyroid Adenoma and Residual Normal Tissue
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE parathyroid adenoma; normal tissue; p53; Ki-67; bcl-2
ID parathyroid adenoma; normal tissue; p53; Ki-67; bcl-2
AB The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.
C1 [Hadar, Tuvia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Shvero, Jacob] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Yaniv, Eitan] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Ram, Eduard] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Surgery ATel Aviv, Israel.
[Shvili, Itzhak] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Koren, Rumelia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Pathology, Ramat Aviv, 69978 Tel Aviv, Israel.
RP Koren, R (reprint author), Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Pathology, 69978 Tel Aviv, Israel.
EM rumelia@isdumail.co.il
CR Abbona GC, Papotti M, Gasparri G, et al: Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining. Hum Pathol 26:135-138, 1995
Arnold A, Staunton CE, Kim HG, et al: Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. N Engl J Med 318: 658-662, 1988
Arnold A, Kim HG: Clonal loss of one chromosome 11 in a parathyroid adenoma. J Clin Endocrinol Metab 69:496-499, 1989
Carson DA, Ribeiro JM: Apoptosis and disease. Lancet 341:1251-1254, 1993
Cryns VL, Rubio MP, Thor AD, et al: p53 abnormalities in human parathyroid carcinoma. J Clin Endocrinol Metab 78:1320-1324, 1994
Dervan PA, Magee HM, Buckley C, et al: Proliferating cell nuclear antigen counts in formalin-fixed paraffin-embedded tissue correlate with Ki-67 in fresh tissue. Am J Clin Pathol 97:S21-28, 1992
Ghandur-Mnaymneh L, Kimura N: The parathyroid adenoma. A histopathologic definition with a study of 172 cases of primary hyperparathyroidism. Am J Pathol 115:70-83, 1984
Greenblatt MS, Bennett WP, Hollstein M, et al: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:855-4878, 1994
Gulkesen KH, Kilicarslan B, Altunbas HA, et al: EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study. APMIS 109:870-874, 2001
Hakim JP, Levine MA: Absence of p53 point mutations in parathyroid adenoma and carcinoma. J Clin Endocrinol Metab 78:103-106, 1994
Hockenbery DM, Zutter M, Hickey W, et al: BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA 88:6961-6965, 1991
Hollstein MC, Peri L, Mandard AM, et al: Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. Cancer Res 51:4102-4106, 1991
Karak AK, Sarkar C, Chumber S, Tandon N: MIB-1 proliferative index in parathyroid adenoma & hyperplasia. Ind J Med Res 105: 235-238, 1997
Kayath MJ, Martin LC, Vieira JG, et al: A comparative study of p53 immunoexpression in parathyroid hyperplasias secondary to uremia, primary hyperplasias, adenomas and carcinomas. Eur J Endocrinol 139:78-83, 1998
Kishikawa S, Shan L, Ogihara K, et al: Overexpression and genetic abnormality of p53 in parathyroid adenomas. Pathol Int 49:853-857, 1999
LeBrun DP, Warnke RA, Cleary ML: Expression of bcl-2 in fetal tissues suggests a role in morphogenesis. Am J Pathol 142:743-753, 1993
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Lu QL, Abel P, Foster CS, et al: bcl-2: role in epithelial differentiation and oncogenesis. Hum Pathol 27:102-110, 1996
Martin LN, Kayath MJ, Vieira JG, et al: Parathyroid glands in uraemic patients with refractory hyperparathyroidism: histopathology and p53 protein expression analysis. Histopathology 33:46-51, 1998
Naccarato AG, Marcocci C, Miccoli P, et al: Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues. J Endocrinol Invest 21:136-141, 1998
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Ricci F, Mingazzini PL, Sebastiani V, et al: p53 as a marker of differentiation between hyperplastic and adenomatous parathyroids. Ann Diagn Pathol 6:229-235, 2002
Stojadinovic A, Hoos A, Nissan A, et al: Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol 34:54-64, 2003
Szende B, Farid P, Vegso G, et al: Apoptosis and P53, Bcl-2 and Bax gene expression in parathyroid glands of patients with hyperparathyroidism. Pathol Oncol Res 10: 98-103, 2004
Szende B: The occurrence and significance of apoptosis in tumors. Magy Onkol 48: 215-219, 2004
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Vargas MP, Vargas HI, Kleiner DE, et al: The role of prognostic markers, MIB-1, RB, and bcl-2, in the diagnosis of parathyroid tumors. Mod Pathol 10:12-17, 1997
Wang W, Johansson H, Kvasnicka T, et al: Detection of apoptotic cells and expression of Ki-67 antigen, Bcl-2, p53 oncoproteins in human parathyroid adenoma. APMIS 104:789-796, 1996
Williams GT: Programmed cell death: apoptosis and oncogenesis. Cell 65:1097-1098, 1991
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 45
EP 49
PG 5
ER
PT J
AU Koch, JH
Hau, P
AF Koch, J Horst
Hau, Peter
TI ROC Analysis as an Additional Method to Characterize Time to Event Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE ROC; Kaplan-Meier; brain tumor
ID ROC; Kaplan-Meier; brain tumor
AB The receiver operating characteristic (ROC) is predominantly used to assess the discriminant power of diagnostic tests. The present paper proposes this method as an additional alternative to compare survival data of in oncology or related fields. Survival data of brain tumors were analysed with conventional Kaplan-Meier method and ROC. The Area und the Curve (ROC-curve) gives additional illustrative information to distinguish between two therapeutic approaches and low or high grade brain tumors.
C1 [Koch, J Horst] Neurologische Universitatsklinik Regensburg, Universitatsstrasse 84, 93053 Regensburg, Germany.
[Hau, Peter] Neurologische Universitatsklinik Regensburg, Universitatsstrasse 84, 93053 Regensburg, Germany.
RP Koch, JH (reprint author), Neurologische Universitatsklinik Regensburg, 93053 Regensburg, Germany.
EM horst.koch@medbo.de
CR Altman D. Practical Statistics for Medical Research. Chapman and Hall. NY 1991
Jensen K, Muller H-H, Schafer H. Regional confidence bands for ROC curves. Statistics in Medicine 19: 493-509, 2000
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. J. Wiley, NY 1980
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 50
EP 52
PG 3
ER
PT J
AU Bal, N
Kayaselcuk, F
Polat, A
Bolat, F
Yilmaz, Z
Tuncer, I
AF Bal, Nebil
Kayaselcuk, Fazilet
Polat, Ay?e
Bolat, Filiz
Yilmaz, Zerrin
Tuncer, Ilhan
TI Familial Cystic Nephroma in Two Siblings with Pleuropulmonary Blastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Cystic nephroma; familial tumors; pleuropulmonary blastoma
ID Cystic nephroma; familial tumors; pleuropulmonary blastoma
AB Cystic nephroma (CN) and pleuropulmonary blastoma (PPB) are rare tumors. In the cases presented here, a 13-month-old boy underwent right radical nephrectomy for CN. From the family history we learned that four years ago the patient’s older sister underwent left radical nephrectomy for CN at a different center when she was 4 years old. A lung tumor was detected in the sister one year after nephrectomy. Biopsy from the lung tumor revealed PPB, and the sister died within one year after biopsy. To the knowledge of the authors, these cases represent the second reported familial occurrence of CN and the fourth of CN and PPB.
C1 [Bal, Nebil] Baskent University, Department of Pathology, Adana Hastanesi, Yure ir, 01250 Adana, Turkey.
[Kayaselcuk, Fazilet] Baskent University, Department of Pathology, Adana Hastanesi, Yure ir, 01250 Adana, Turkey.
[Polat, Ay?e] Mersin University School of Medicine, Department of PathologyMersin, Turkey.
[Bolat, Filiz] Baskent University, Department of Pathology, Adana Hastanesi, Yure ir, 01250 Adana, Turkey.
[Yilmaz, Zerrin] Baskent University Faculty of Medicine, Department of Medical Biology and GeneticsAnkara, Turkey.
[Tuncer, Ilhan] Baskent University, Department of Pathology, Adana Hastanesi, Yure ir, 01250 Adana, Turkey.
RP Bal, N (reprint author), Baskent University, Department of Pathology, 01250 Adana, Turkey.
EM nebilbal@baskent-adn.edu.tr
CR Delahunt B, Thomson KJ, Ferguson AF, et al: Familial cystic nephroma and pleuropulmonary blastoma. Cancer 71: 1338- 1342, 1993
Ishida Y, Kato K, Kigasawa H, et al: Synchronous occurrence of pleuropulmonary blastoma and cystic nephroma: possible genetic link in cystic lesions of the lung and the kidney. Med Pediatr Oncol 35: 85-87, 2000
Kiziltepe TT, Patrick E, Alvarado C, et al: Pleuropulmonary blastoma and ovarian teratoma. Pediatr Radiol 29: 901-903, 1999
Priest JR, Watterson J, Strong L, et al: Pleuropulmonary blastoma: a marker for familial disease. J Pediatr 128: 220-224, 1996
Manivel JC, Priest JR, Watterson J, et al: Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer 62: 1516-1526, 1988
Lallier M, Bouchard S, Di Lorenzo M, et al: Pleuropulmonary blastoma: a rare pathology with an even rarer presentation. J Pediatr Surg 34: 1057-1059, 1999
Knudson AG. On a new genetic syndrome. Med Pediatr Oncol 35: 428, 2000
Sebire NJ, Rampling D, Malone M, et al: Gains of chromosome 8 in pleuropulmonary blastomas of childhood. Pediatr Dev Pathol 5: 221-222, 2002
Sacher P, Willi UV, Niggli F, et al: Cystic nephroma: a rare benign renal tumor. Ped Surg Int 13: 197-199, 1998
Kural AR, Obek C, Ozbay G, et al: Multilocular cystic nephroma: an unusual localization. Urology 52: 897-899, 1998
Fujimoto K, Samma S, Fukui Y, et al: Spontaneously ruptured multilocular cystic nephroma. Int J Urol 9: 183-186, 2002
Sharma S, Nagar R, Singh K, et al: Cystic nephroma: an unusual renal lesion. J Urol 163: 1860, 2000
Polat P, Suma S, Celenk C, et al: Quiz case of the month. Multilocular cystic nephroma, MLCN). Eur Radiol 7: 757-758, 1997
Verma RS, Babu A: Human Chromosomes Principles and Techniques 2nd Edition. Mc Graw Hill, New York, 1995, pp. 6-71
Verma RS, Babu A: Human Chromosomes Principles and Techniques 2nd Edition. Mc Graw Hill, New York, 1995, pp. 72-133
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 53
EP 56
PG 4
ER
PT J
AU Rieker, JR
Aulmann, S
Schnabel, AP
Sack, FU
Herwart, FO
Mechtersheimer, G
Schirmacher, P
Blaker, H
AF Rieker, J Ralf
Aulmann, Sebastian
Schnabel, A Philipp
Sack, Falk-Udo
Herwart, F Otto
Mechtersheimer, Gunhild
Schirmacher, Peter
Blaker, Hendrik
TI Cystic Thymoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE thymic cysts; cystic thymoma; micronodular thymoma
ID thymic cysts; cystic thymoma; micronodular thymoma
AB Thymic cysts are rare lesions located along the anatomical course of the third pharyngeal pouch. While most of the cases represent congenital cysts, they may also be related to neoplasms. We report a case of a micronodular thymoma with lymphoid stroma, which was completely built of small cysts, discuss the pathologic features of this tumor type and review the etiology and other aspects of thymic cysts.
C1 [Rieker, J Ralf] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Aulmann, Sebastian] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Schnabel, A Philipp] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Sack, Falk-Udo] University Hospital, Department of Cardiac SurgeryHeidelberg, Germany.
[Herwart, F Otto] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Mechtersheimer, Gunhild] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Schirmacher, Peter] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Blaker, Hendrik] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
RP Rieker, JR (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
EM ralf.rieker@med.uni-heidelberg.de
CR Bradford ML, Mahon HW, Grow JB: Mediastinal cysts and tumors. Surg Gynecol Obstet 85: 467-491, 1947
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Guba AM jr, Adam AE, Jaques DA, et al: Cervical presentation of thymic cysts. Am J Surg 136:430-436, 1978
Hyde TL, Sellers ED, Owen M: Thymic cyst of the neck: report of a case. Tex State J Med 39:539-540, 1944
Indeglia RA, Shea MA, Grage TB: Congenital cysts of the thymus gland. Arch Surg 94:149-152, 1967
Inoue M, Starostik P, Zettl A, et al: Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 63:3708- 3715, 2003.
Krech WG, Storey CF, Umiker WC: Thymic cysts: a review of the literature and report of two cases. J Thorac Surg 27: 477- 493, 1954
Leong AS, Brown JH: Malignant transformation in a thymic cyst. Am J Surg Pathol 8:471-475, 1984
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Moran CA, Suster S: Thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction: a clinicopathologic study of 25 cases. Am J Surg Pathol 25:1086- 1090, 2001
Murray JA, Parker AC: Mediastinal Hodgkin’s disease and thymic cysts. Acta Haematol, Basel, 71:282-284, 1984
Penzel R, Hoegel J, Schmitz W, et al: Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka. Int J Cancer 105:494-498, 2003
Pollosson A, Piery M: Un cas d’epithelioma primitif du Thymus. Provinc Med 16:1-4, 1901
Rippert H: Die Entwicklungsstorung der Thymusdruse bei kongenitaler Lues. Frankfurt Z Pathol 11:209-218, 1912
Rosai J, Levine GD: Tumors of the thymus. In: Atlas of Tumor Pathology, 2nd series, fasc 13. Armed Forces Institute of Pathology, Washington DC, 1976, pp 48-49, 207-211,
Smart J: A case of large thymic cyst successfully removed from the anterior mediastinum. Br J Tuberc 41: 84-88, 1947
Suster S, Moran CA: Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol 20:1469-1480, 1996
Suster S, Moran CA: Micronodular thymoma with lymphoid Bcell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm. Am J Surg Pathol 23:955-962, 1999
Suster S, Rosai J: Multilocular thymic cyst: an acquired reactive process. Study of 18 cases. Am J Surg Pathol 15: 388-398, 1991
Suster S, Rosai J: Cystic thymomas. A clinicopathologic study of ten cases. Cancer 69:92-97, 1992
Tateyama H, Saito Y, Fujii Y, et al: The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia. Histopathology 38: 519-527, 2001
Thomas De Montpreville V, Zemoura L, Dulmet E: Thymoma with epithelial micronodules and lymphoid hyperplasia: six cases of a rare and equivocal subtype. Ann Pathol 22:177-182, 2002
Wychulis AR, Payne WS, Clagett OT, Woolner LB: Surgical treatment of mediastinal tumors - a 40 year experience. J Thorac Cardiovasc Surg 62: 379-392, 1971
Zettl A, Strobel P, Wagner K, et al: Recurrent genetic aberrations in thymoma and carcinoma. Am J Pathol 157:257-266, 2000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2005
VL 11
IS 1
BP 57
EP 60
PG 4
ER
PT J
AU Kopper, L
Zalatnai, A
Timar, J
AF Kopper, Laszlo
Zalatnai, Attila
Timar, Jozsef
TI Genomics of Pancreatic Cancer: Does It Make Any Improvement in Diagnosis, Prognosis and Therapy?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE pancreatic cancer; genomics
ID pancreatic cancer; genomics
AB Pancreatic cancer (PanC) is an extremely lifethreatening neoplasm due to its late discovery, rapid progression and resistance to chemo- and radiotherapy. In the past years a significant research attention turned to this cancer. Extensive genomic analysis of PanC revealed numerous alterations, however, none of them emerged yet as a key regulator of tumor progression. Our increasing knowledge on the molecular targets in various cancer types started to change their management. Examples of success of the molecular therapies (in CML, GIST, NSCLC) may initiate more activity in pancreatic cancer as well.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor ProgressionBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Schleger C, Arens N, Zentgraf H, et al: Identification of frequent chromosomal aberrations in ductal adenocarcinoma of the pancreas by comparative genomic hybridization, CGH). J Pathol 191: 27-32, 2000
Mahlamaki EH, Hoglund M, Gorunova L, et al: Comparative genomic hybridization reveals frequent gains of 20q, 8q, 11q, 12p, and 17q, and losses of 18q, 9p, and 15q in pancreatic cancer. Genes Chromosomes Cancer 204: 383-391, 1997
Holtzmann K, Kohlhammer H, Schwaenen C, et al: Genomic DNA-chip hybridization reveals a higher incidence of genomic amplifications in pancreatic cancer than conventional comparative genomic hybridization and leads to the identification of novel candidate genes. Cancer Res 64: 4428-4444, 2004
Okami J, Simeone DM, Logsdon CD: Silencing of the hypoxiainducible cell death protein BNIP3 in pancreatic cancer. Cancer Res 64: 5338-5346, 2004
Prasad NB, Biankin AV, Fukushima N, et al: Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res 65: 1619-1626, 2005
Bardeesy N, DePinho RA: Pancreatic cancer biology and genetics. Nat Rev Cancer 2: 897-909, 2002
Juhasz M, Nitsche B, Malfertheiner P, Ebert MPA: Implications of the growth factor alterations in the treatment of pancreatic cancer. Mol Cancer 2: 5, 2003
Iacobuzio-Donahue CA, Asfaq R, Maitra A, et al: Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res 63: 8614-8622, 2003
Shen J, Person MD, Zhu J, et al: Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res 64: 9018-9026, 2004.
Suwa H, Ohshio G, Arao S, et al: Immunohistochemical localization of P-glycoprotein and expression of the multidrug resistance- 1 gene in human pancreatic cancer: relevance to indicator of better prognosis. Jpn J Cancer Res 87: 641-649, 1996
Watanabe I, Hasabe T, Sasaki S et al: Advanced pancreatic ductal cancer: fibrotic focus and b-catenin expression correlate with outcome. Pancreas 26: 326-333, 2003
Ougolkov AV, Fernandez-Zapico ME, Savoy DN, et al: Glycogen synthase kinase-3b participates in nuclear factor kB-mediated gene transcription and cell survival in pancreatic cancer cells. Cancer Res 65: 2076-2081, 2005
Muerkoster S, Arlt A, Sipos B, et al: Increased expression of the E3-ubiquitin ligase receptor subunit bTRCP1 relates to constitutive nuclear factor-kB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res 65: 1316-1324, 2005
Bai J, Sui J, Demirjian A, et al: Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: tumor necrosis factor- related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro. Cancer Res 65: 2344-2352, 2005
Jiang XT, Tao HQ, Zou SC: Detection of serum tumor markers in the diagnosis and treatment of patients with pancreatic cancer. Hepatobiliary Pancreatic Dis Inst 3: 363-468, 2004
Louhimo J, Alfthan H, Stenman UH, Haglund C: Serum HCG beta and CA 72-4 are stronger prognostic factors than CEA, CA 19-9 and CA 242 in pancreatic cancer. Oncology 66: 126- 131, 2004
Suzuki K, Aiura K, Kitagou M, et al: Platelets counts closely correlate with the disease-free survival interval of pancreatic cancer patients. Hepatogastroenterology 51: 847-853, 2004
Timar J, Tovari J, Raso E, et al: Thrombocyte-mimicry of cancer cells: rationale for the prevention and treatment of hematogenous dissemination. Oncology, 2005, in press)
Logsdon CD, Simeone DM, Binkley C, et al: Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identified multiple genes differentially regulated in pancreatic cancer. Cancer Res 63: 2649-2657, 2003
Li YJ, Meng YX, Ji XR. Relationship between expression of Ecadherin and alpha-catenin and biological behaviors of human pancreatic cancer. Hepatobiliary Pancreat Dis Int 2: 471-477, 2003
Keleg S, Buchler P, Ludwig R, et al: Invasion and metastasis in pancreatic cancer. Mol Cancer 2:14, 2003
Stanton KJ, Sidner RA, Miller GA, et al: Analysis of Ki-67 antigen expression, DNA proliferative fraction, and survival in resected cancer of the pancreas. Am J Surg 186: 486-492, 2003
Fukumoto A, Ikeda N, Sho M, et al: Prognostic significance of localized p27Kip1 and potential role of Jab1/CSN5 in pancreatic cancer. Oncol Rep 11: 277-284, 2004
Juuti A, Nordling S, Louhimo J, et al: Loss of p27 expression is associated with poor prognosis in stage I-II pancreatic cancer. Oncology 65: 371-377, 2003
Jinfeng M, Kimura W, Hirai I, et al: Expression off MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis. Int J Gastrointest Cancer 34: 9-18, 2003
Ueda S, Ogata S, Tsuda H, et al: The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 29: e1-8, 2004
Schlieman MG, Fahy BN, Ramsamooj R, et al: Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 89: 2110-2115, 2003
Grutzmann R, Luttges J, Sipos B, et al: ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma. Br J Cancer 90: 1053- 1058, 2004
Fukunaga A, Miyamoto M, Cho Y, et al: CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28: e26-31, 2004
Jaster R: Molecular regulation of pancreatic stellate cell function. Mol Cancer 3: 26, 2004
Sausville EA: The challenge of pathway and environmentmediated drug resistance. Cancer Metastasis Rev 20: 117-122, 2001
Elad-Sfadia G, Haklai R, Ballan E, et al: Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase. J Biol Chem 277: 37169-37175, 2002
Kitada T, Seki S, Sakaguchi H, et al: Clinicopathological significance of hypoxia-inducible factor-1a expression in human pancreatic carcinoma. Histopathology 43: 550-555, 2003
Duffy JP, Eibl G, Reber HA, Hines OJ: Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer. Mol Cancer 2: 12, 2003
Silletti S, Paku S, Raz A: Tumor cell motility and metastasis. Autocrine motility factor as an example of ecto/exoenzyme cytokines. Pathol Oncol Res 3: 230-254, 1997
Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3: 721-732, 2003
Kuwahara K, Sasaki T, Kuwada Y, et al: Expression of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas 26: 344-349, 2003
Ikeda N, Nakajima Y, Tokuhara T, et al: Clinical significance of aminopeptide N/CD13 expression in human pancreatic carcinoma. Clin Cancer Res 9: 1503-1508, 2003
Uehara H, Miyamoto M, Kato K, et al: Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res 64: 3533-3537, 2004
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 69
EP 73
PG 5
ER
PT J
AU Croce, VM
Rabassa, EM
Pereyra, A
Segal-Eiras, A
AF Croce, V Maria
Rabassa, E Martin
Pereyra, Adrian
Segal-Eiras, Amada
TI Influence of Sialic Acid Removal on MUC1 Antigenic Reactivity in Head and Neck Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck carcinoma; MUC1; carbohydrate antigens; sialic acid
ID head and neck carcinoma; MUC1; carbohydrate antigens; sialic acid
AB To investigate the influence of sialic acid removal on MUC1 peptidic and carbohydrate epitope reactivity in head and neck squamous cell carcinoma (HNSCC), tumor samples belonging to 24 HNSCC patients were studied by standard immunohistochemistry (IHC) with and without desialylation with 0.1 U/ml neuraminidase. From each tumor sample, subcellular fractions were obtained and analyzed by SDS-PAGE and Western blotting (WB). Three monoclonal antibodies (MAbs) were used: C595 MAb directed to MUC1 protein core, an anti-Tn hapten MAb, and an anti-sTn hapten MAb; a comparative analysis between desialylated and sialylated samples was performed. By IHC without neuraminidase treatment, 19 of 24 samples reacted with anti-MUC1 peptidic epitope, while Tn hapten was not detected and sTn was found in 1 of 24 cases. Desialylation increased either the number of reacting cells or the intensity of the reaction with C595 and anti-Tn MAbs, and some negative samples became positive. On the other hand, sTn expression decreased with desialylation. By WB, several bands from >200 to 25 kDa were found; desialylation increased high-molecular-weight bands, diminishing the detection of low-molecular-weight ones. The use of desialylation is a suitable treatment that contributes to the exposure of MUC1-associated epitopes, which may be related to the spreading of HNSCC.
C1 [Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Rabassa, E Martin] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Pereyra, Adrian] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM as-eiras@netverk.com.ar
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 74
EP 81
PG 8
ER
PT J
AU Komlosi, K
Kellermayer, R
Maasz, A
Havasi, V
Hollody, K
Vincze, O
Merkli, H
Pal, E
Melegh, B
AF Komlosi, Katalin
Kellermayer, Richard
Maasz, Anita
Havasi, Viktoria
Hollody, Katalin
Vincze, Olga
Merkli, Hajnalka
Pal, Endre
Melegh, Bela
TI Maternally Inherited Deafness and Unusual Phenotypic Manifestations Associated with A3243G Mitochondrial DNA Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mtDNA A3243G; tRNALeu(UUR); mitochondrial disease; MELAS; deafness
ID mtDNA A3243G; tRNALeu(UUR); mitochondrial disease; MELAS; deafness
AB The mitochondrial DNA A3243G transition is a fairly common mutation which often associates with a MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) phenotype, however, a broad variety in the associated clinical picture has also been described. The patient reported here developed a generalized seizure at age 12, which was followed by bilateral hearing loss and occasional fatigue. The maternal inheritance pattern of hearing loss pointed to a possible mitochondrial origin, which was confirmed by molecular analysis of the mitochondrial DNA, revealing a heteroplasmic A3243G transition. Interestingly, muscle biopsy showed ragged-red fibers in the proband, which is unusual in the deafness-associated forms of this mitochondrial disorder. In addition to hearing impairment in four generations of the family, fatal cerebral embolization in the mother and fatal heart attack in the maternal grandmother (both at age 33) also occurred. On the contrary, diabetes, which usually accompanies the hearing loss variant, was specifically absent in all generations. The unusual manifestations associated with this mutation somewhat differentiate this family from the already known variants.
C1 [Komlosi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
[Kellermayer, Richard] University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
[Havasi, Viktoria] University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
[Hollody, Katalin] University of Pecs, Department of NeurologyPecs, Hungary.
[Vincze, Olga] County Hospital of BaranyaPecs, Hungary.
[Merkli, Hajnalka] University of Pecs, Department of NeurologyPecs, Hungary.
[Pal, Endre] University of Pecs, Department of NeurologyPecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
EM Bela.Melegh@aok.pte.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 82
EP 86
PG 5
ER
PT J
AU Bircan, S
Candir, O
Kapucuoglu, N
AF Bircan, Sema
Candir, Ozden
Kapucuoglu, Nilgun
TI The Effect of Tumor Invasion Patterns on Pathologic Stage of Bladder Urothelial Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE urinary bladder; urothelial carcinoma; invasion pattern
ID urinary bladder; urothelial carcinoma; invasion pattern
AB The aim of this study was to investigate tumor invasion pattern, its heterogeneity and association with histopathological features and stage in invasive urothelial carcinoma of the bladder. We studied 62 cases of invasive urothelial carcinoma of the bladder. World Health Organization (WHO) 1973, WHO/ISUP 1998 and WHO 1999 systems were used for tumor grading. Pathologic staging of each case was done according to 1997 TNM system. During evaluation of the slides three main tumor invasion patterns were detected: ''nodular”, ''trabecular” and ''infiltrative”. In addition, homogeneity or heterogeneity of invasion patterns was also recorded for each case. Of sixty-two invasive cases, 17 (27%) had nodular, 36 (58%) trabecular, and 9 (15%) infiltrative invasion pattern. There was a statistically significant difference between invasion patterns in relation to pathologic stage (pT) (p=0.001), but not to grade. Of the 17 cases with nodular invasion pattern and 36 tumors with trabecular invasion pattern, 13 (77%) and 26 (72%) were pT1, respectively, whereas 8 of 9 infiltrative cases (89%) were advanced stage (pT2-3). According to heterogeneity, forty-two cases (68%) had homogeneous, while the remaining 20 (32%) had heterogeneous invasion pattern. Of the 42 homogeneous cases 34 (81%) were pT1, whereas 14 of 20 heterogeneous cases (70%) were advanced stage (p=0.000). The different invasion patterns seem to have a large impact on pathologic stage, especially the infiltrative pattern. In addition, invasion heterogeneity appears to be of value in determination of biologic aggressiveness in urothelial carcinoma.
C1 [Bircan, Sema] Suleyman Demirel University, Faculty of Medicine, Department of PathologyIsparta, Turkey.
[Candir, Ozden] Suleyman Demirel University, Faculty of Medicine, Department of PathologyIsparta, Turkey.
[Kapucuoglu, Nilgun] Suleyman Demirel University, Faculty of Medicine, Department of PathologyIsparta, Turkey.
RP Bircan, S (reprint author), Suleyman Demirel University, Faculty of Medicine, Department of Pathology, Isparta, Turkey.
EM bircans2000@yahoo.com
CR Lapham RL, Grignon D, Ro JY: Pathologic prognostic parameters in bladder urothelial biopsy transurethral resection, and cystectomy specimens. Semin Diagn Pathol 14: 109-122, 1997
Lopez-Beltran A, Cheng L: Stage pT1 bladder carcinoma: diagnostic criteria, pitfalls and prognostic significance. Pathology 35: 484-491, 2003
Cheng L, Weaver AL, Bostwick DG: Predicting extravesical extension of bladder carcinoma: A novel method based on micrometer measurement of the depth of invasion in transurethral resection specimens. Urology 55: 668-672, 2000
Bostwick DG, Mikuz G: Urothelial papillary, exophytic, neoplasms. Virchows Arch 441: 109-116, 2002
Amin MB, Gomez JA, Young RH: Urothelial transitional cell carcinoma with endophytic growth patterns: A discussion of patterns of invasion and problems associated with assessment of invasion in 18 cases. Am J Surg Pathol 21: 1057-1068, 1997
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Farrow GM, Utz DC: Observations on microinvasive transitional cell carcinoma of the urinary bladder. Clin Oncol 1: 609- 615, 1982
Bostwick DG, Ramnani D, Cheng L: Diagnosis and grading of bladder cancer and associated lesions. Urol Clin North Am 26: 493-507, 1999
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Jimenez RE, Gheiler E, Oskanian P, et al: Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival. Am J Surg Pathol 24: 980-987, 2000
Cheng L, Neumann RM, Nehra A, et al: Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma. Cancer 88: 1663-1670, 2000
Billis A, Carvalho RB, Mattos AC, et al: Tumor grade heterogeneity in urothelial bladder carcinoma: Proposal of a system using combined numbers. Scand J Urol Nephrol 35: 275-279, 2001
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Cheng L, Neumann RM, Weaver AL, et al: Predicting cancer progression in patients with stage T1 bladder carcinoma. J Clin Oncol 17: 3182-3187, 1999
Cheng L, Weaver AL, Neumann RM, et al: Substaging of T1 bladder carcinoma based on the depth of invasion as measured by micrometer: A new proposal. Cancer 86: 1035-1043, 1999
Smits G, Schaafsma E, Kiemeney L, et al: Microstaging of pT1 transitional cell carcinoma of the bladder: Identification of subgroups with distinct risks of progression. Urology 52: 1009- 1014, 1998
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 87
EP 91
PG 5
ER
PT J
AU Baki, M
AF Baki, Marta
TI What is the Role of Letrozole in Adjuvant Breast Carcinoma Setting?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
AB A meeting for Letrozole clinical investigators was organized in Orlando, joined to ASCO Conference, 2005, in order to review the newest data in adjuvant breast cancer trials.
C1 [Baki, Marta] Szent Margit Hospital, V. Department of Internal Medicine - OncologyBudapest, Hungary.
RP Baki, M (reprint author), Szent Margit Hospital, V. Department of Internal Medicine - Oncology, Budapest, Hungary.
CR Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. New Engl J Med 349: 1793-1802, 2003
Wasan KM, Goss PE, Pritchard PH, et al. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years adjuvant tamoxifen, NCIC CTG MA.17L). Ann Oncol 16: 707-715, 2005
Thurlimannn B et al for the BIG I-98 Collaborative coordinated by the International Breast Cancer Study Group. Letrozole as adjuvant endocrine therapy for postmenopausal women with receptor positive breast cancer. First results of IBCSG 18-98/BIG I-98. Presented at 9th International Conference on Primary Therapy of Early Breast Cancer: January 26-29, 2005, St. Gallen, Abstr. S4
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 91
EP 91
PG 1
ER
PT J
AU Simsa, P
Teillaud, JL
Stott, ID
Toth, J
Kotlan, B
AF Simsa, Peter
Teillaud, Jean-Luc
Stott, I David
Toth, Jozsef
Kotlan, Beatrix
TI Tumor-Infiltrating B Cell Immunoglobulin Variable Region Gene Usage in Invasive Ductal Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunoglobulin variable region; breast ductal carcinoma; tumor-infiltrating lymphocytes
ID immunoglobulin variable region; breast ductal carcinoma; tumor-infiltrating lymphocytes
AB A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients’ survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.
C1 [Simsa, Peter] National Medical Center, Department of Hematology and Stem Cell Transplantation, Szabolcs u 33-35., H-1135 Budapest, Hungary.
[Teillaud, Jean-Luc] Centre de Recherches Biomedicales des Cordeliers, INSERM U255Paris, France.
[Stott, I David] University of Glasgow, Western Infirmary, Division of Immunology, Infection and InflammationGlasgow, Scotland, UK.
[Toth, Jozsef] National Institute of OncologyBudapest, Hungary.
[Kotlan, Beatrix] National Medical Center, Department of Hematology and Stem Cell Transplantation, Szabolcs u 33-35., H-1135 Budapest, Hungary.
RP Kotlan, B (reprint author), National Medical Center, Department of Hematology and Stem Cell Transplantation, H-1135 Budapest, Hungary.
EM KotlanB@netscape.net
CR Hadden JW: The immunology and immunotherapy of breast cancer: an update. Int J Immunopharmacol 21: 79-101, 1999
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Kotlan B, Simsa P, Teillaud JL et al: Novel ganglioside antigen identified by B cells in human medullary breast carcinomas. The proof of principle concerning the infiltrating B lymphocytes. J Immun, 2005, in press)
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 92
EP 97
PG 6
ER
PT J
AU Kamali-Sarvestani, E
Gharesi-Fard, B
Sarvari, J
Talei, AAR
AF Kamali-Sarvestani, Eskandar
Gharesi-Fard, Behrouz
Sarvari, Jamal
Talei, Abd-Al-Rasoul
TI Association of TNF-α and TNF-β Gene Polymorphism with Steroid Receptor Expression in Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; steroid receptors; TNF; polymorphism
ID breast cancer; steroid receptors; TNF; polymorphism
AB The presence of estrogen and progesterone receptors is correlated with good prognosis in breast cancer. The effect of TNF-α on down-regulation of estrogen receptor and blocking the proliferative response of breast cancer cells to estradiol have been demonstrated. However, the effect of TNFA and TNFB gene polymorphisms on the expression of steroid receptors in breast cancer cells is not well documented. Therefore, 160 breast cancer patients were recruited to investigate the association of TNFA and TNFB gene polymorphism with the level of steroid receptor expression. This association was not found to be significant for TNFA polymorphism and estrogen receptor expression (p=0.07). However, when combined genotypes of TNFA and TNFB polymorphism was considered, homozygous patients for lower TNF-α producer genotypes (TNFA1/A1 and TNFB1/B1) showed significantly higher progesterone receptor expression (p=0.041). Our findings indicate that TNFA and TNFB polymorphisms may be associated with the levels of steroid receptor expression in breast cancer patients. Further studies on a larger group of breast cancer patients are recommended.
C1 [Kamali-Sarvestani, Eskandar] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Gharesi-Fard, Behrouz] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Sarvari, Jamal] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Talei, Abd-Al-Rasoul] Medical School, Shiraz University of Medical Sciences, Department of SurgeryShiraz, Iran.
RP Kamali-Sarvestani, E (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM immunol2@sums.ac.ir
CR Akerblom, IW, Mellon, PL: Nuclear Hormone Receptors, Ed: Parker MG), Academic Press Ltd, London 1991, pp 175-196
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Clark GM, McGuire WL: Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 15: 20-25, 1998
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 99
EP 102
PG 4
ER
PT J
AU Cavalcanti, dBCF
Alves, AFV
Pereira, J
Kanamura, TC
Wakamatsu, A
Saldanha, BL
AF Cavalcanti, de Barros Correia Fernanda
Alves, Avancini Ferreira Venancio
Pereira, Julio
Kanamura, T Cristina
Wakamatsu, Alda
Saldanha, Balthazar Luis
TI Proliferative Lesions of Prostate: a Multivariate Approach to Differential Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostatic hyperplasia; prostatic intraepithelial neoplasia; atypical small acinar proliferation; prostate cancer; histological features
ID prostatic hyperplasia; prostatic intraepithelial neoplasia; atypical small acinar proliferation; prostate cancer; histological features
AB Prostatic needle biopsies from 142 patients were studied: 61 cases were ''benign”, 19 atypical small acinar proliferation, 31 high-grade prostatic intraepithelial neoplasia, and 31 adenocarcinoma. Using univariate analysis of 46 previously described morphological features, 16 variables were selected, which were followed by multivariate discriminant analysis. Of these parameters, seven (glandular fusion, crystalloids, nucleolomegaly, papillary architecture, visibility of basal cell layer, areas of normal luminal cell nucleus/cytoplasm ratio and areas of high luminal cell nucleus/cytoplasm ratio) remained significant in discriminating the groups. Multivariate analysis selected a small panel of histological features as those most helpful in the differential diagnosis of proliferative lesions in prostate biopsies.
C1 [Cavalcanti, de Barros Correia Fernanda] Sao Paulo University School of Medicine, Department of Pathology, Av. Dr. Arnaldo 455, 01246-802 Sao Paulo, Brazil.
[Alves, Avancini Ferreira Venancio] Sao Paulo University School of Medicine, Department of Pathology, Av. Dr. Arnaldo 455, 01246-802 Sao Paulo, Brazil.
[Pereira, Julio] Sao Paulo University School of Medicine, Department of Pathology, Av. Dr. Arnaldo 455, 01246-802 Sao Paulo, Brazil.
[Kanamura, T Cristina] Sao Paulo Public Health Service, Adolfo Lutz Institute, Division of PathologySao Paulo, Brazil.
[Wakamatsu, Alda] Sao Paulo Public Health Service, Adolfo Lutz Institute, Division of PathologySao Paulo, Brazil.
[Saldanha, Balthazar Luis] Sao Paulo University School of Medicine, Department of Pathology, Av. Dr. Arnaldo 455, 01246-802 Sao Paulo, Brazil.
RP Alves, AFV (reprint author), Sao Paulo University School of Medicine, Department of Pathology, 01246-802 Sao Paulo, Brazil.
EM venancio@uol.com.br
CR IBGE: DPE/DEPIS; MS/InCA/CONPREV/Divisao de Epidemiologia e Avaliacao S/SIM- Sistema de Informacao sobre mortalidade [http:www.ibge.gov.br/], 2000
Arista-Nasr J, Cortes E, Pichardo R: Low grade adenocarcinoma simulating benign glandular lesions in needle prostatic biopsy. Rev Invest Clin 49:37-40, 1997
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Brawer MK: Prostatic intraepithelial neoplasia: A premalignant lesion. Hum Pathol 23: 242-248, 1992
Cheville JC, Bostwick DG: Postatrophic Hyperplasia of the Prostate. Am J Surg Pathol 19:1068-1076, 1995
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Gleason DF, 1992). Histologic grading of prostate cancer. A perspective. Hum Pathol 23: 273-279, 1992
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Iczkowski KA, MacLennan GT, Bostwick DG: Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases. Am J Surg Pathol 21:1489-1495, 1997
Moore RA: Benign hypertrophy of the prostate - a morphological study. J Urol 50: 580-710, 1943
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O’Malley FP, Grignon DJ, Shum DT: Usefulness of immunoperoxidase staining with high molecular weight cytokeratin in the differential diagnosis of small acinar lesions of the prostate gland. Virchows Arch Pathol Anat 417:191-196, 1990
Ximing JY, Lecksell K, Gaudin P, Epstein J: Rare expression of high molecular weight cytokeratin in adenocarcinoma of the prostate gland. A study of 100 cases of metastatic and locally advanced prostate cancer. Am J Surg Pathol 23:147-152, 1999
Amin MB, Tamboli P, Varma M, Srigley JR: Postatrophic hyperplasia of the prostate gland: a detailed analysis of its morphology in needle biopsy specimens. Am J Surg Pathol 23:925-931, 1999
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Ruska KM, Sauvageot J, Epstein JI: Histology and cellular kinetics of prostatic atrophy. Am J Surg Pathol 22:1073-1077, 1998
Leroy X, Aubert S, Villens A, et al: Minimal focus of adenocarcinoma on prostate biopsy: clinicopathological correlations. J Clin Pathol 56: 230-232, 2003
Anton RC, Kattan MW, Chakraborty S, Wheeler TM: Postatrophic hyperplasia of the prostate: lack of association with prostate cancer. Am J Surg Pathol 23:932-936, 1993
Bostwick DG, Amin MB, Dundore P, et al: Architectural patterns of high grade prostatic intraepithelial neoplasia. Hum Pathol 24:298- 310, 1993
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 103
EP 107
PG 5
ER
PT J
AU Matusan, K
Dordevic, G
Mozetic, V
Lucin, K
AF Matusan, Koviljka
Dordevic, Gordana
Mozetic, Vladimir
Lucin, Ksenija
TI Expression of Osteopontin and CD44 Molecule in Papillary Renal Cell Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE papillary renal cell carcinoma; cell adhesion; CD44s antigen; CD44v6 antigen; osteopontin; immunohistochemistry
ID papillary renal cell carcinoma; cell adhesion; CD44s antigen; CD44v6 antigen; osteopontin; immunohistochemistry
AB The aim of the study was to analyze the expression of CD44 adhesion molecule and its ligand osteopontin in papillary renal cell tumors, and to assess the possible prognostic significance of CD44 and osteopontin expression in papillary renal cell carcinomas. The expression of the standard and v6 exon containing isoforms of CD44 molecule, as well as of its ligand osteopontin, was immunohistochemically evaluated in 43 papillary renal cell tumors, which included 5 adenomas and 38 carcinomas. In order to assess their prognostic significance, the results obtained in papillary renal cell carcinomas were compared to usual clinicopathological parameters such as tumor size, histological grade, pathological stage, and Ki-67 proliferation index. Normal renal tissue was negative for CD44s and v6 isoforms, while the expression of osteopontin was found in distal tubular epithelial cells in the form of cytoplasmic granular positivity. CD44s and v6 isoforms were upregulated in 22 (58%) and 12 (32%) out of 38 carcinomas, respectively. Among all clinicopathological parameters examined, we only found significant association of CD44s-positive carcinomas with lower pathological stage (p=0.026). Papillary renal cell adenomas were generally negative for CD44s, except for focal positivity found in one sample. The osteopontin protein was detected in all adenomas and all papillary renal cell carcinomas, except one. Our results show constitutive expression of osteopontin in papillary renal tumors, including papillary renal cell adenomas. The upregulation of CD44s and v6 isoforms, although found in a considerable number of papillary renal cell carcinomas, does not appear to have any prognostic value in this type of renal cancer.
C1 [Matusan, Koviljka] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
[Dordevic, Gordana] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
[Mozetic, Vladimir] Clinical Hospital Center, Department of UrologyRijeka, Croatia.
[Lucin, Ksenija] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
RP Lucin, K (reprint author), Rijeka University School of Medicine, Department of Pathology, 51 000 Rijeka, Croatia.
EM ksenijal@medri.hr
CR Agrawal D, Chen T, Irby R, et al: Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94:513-521, 2002
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Ariztia EV, Subbarao V, Solt DB, et al: Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation. Exp Cell Res 288:257-267, 2003
Brown LF, Papadopoulos-Sergiou A, Berse B, et al: Osteopontin expression and distribution in human carcinomas. Am J Pathol 145:610-623, 1994
Coppola D, Szabo M, Boulware D, et al: Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histogenesis. Clin Cancer Res 10:184-190, 2004
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Delahunt B, Eble JN: Papillary renal cell carcinoma: A clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 10:537-544, 1997
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Lucin K, Matusan K, Dordevic G, et al: The expression of osteopontin in renal cell carcinomas. In: Proceedings of the Second Intercontinental Congress of Pathology., Eds: Soares F, Vassallo J, Torres LFB), Medimond, 2004, p: 151-154
Lucin K, Matusan K, Dordevic G, et al: Prognostic significance of CD44 molecule in renal cell carcinoma. Croat Med J 45:703-708, 2004
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Rittling SR, Chambers AF: Role of osteopontin in tumour progression. Br J Cancer 90:1877-1881, 2004
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Terpe HJ, Storkel S, Zimmer U, et al: Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation. Am J Pathol 148:453-463, 1996
Zbigniew R, Serge J: CD44 and the adhesion of neoplastic cells. J Clin Pathol: Mol Pathol 50:57-71, 1997
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 108
EP 113
PG 6
ER
PT J
AU Cambruzzi, E
Zettler, GC
Alexandre, OPC
AF Cambruzzi, Eduardo
Zettler, Galleano Claudio
Alexandre, Osmar Pereira Claudio
TI Expression of Ki-67 and Squamous Intraepithelial Lesions are Related with HPV in Endocervical Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE endocervical adenocarcinoma; bcl-2; Ki-67; p53; HPV
ID endocervical adenocarcinoma; bcl-2; Ki-67; p53; HPV
AB To estimate the association between human papillomavirus (HPV) status and the expression of p53, Ki-67 and bcl-2 in cases of endocervical adenocarcinoma, and the relation with squamous intraepithelial lesions (SIL) and age, 229 cases were selected, treated between 1995 and 2003 in the Hospital Nossa Senhora da Conceicao. All samples were evaluated by polymerase chain reaction to determine HPV status. Immunohistochemical technique was used to investigate the expression of p53, Ki-67 and bcl-2. The joint occurrence of endocervical adenocarcinoma and SIL were estimated too. In the 229 evaluated cases, 182 cases (79.48%) were associated with the presence of the HPV. The most common types were HPV18 (93 cases – 51.09%) and HPV16 (62 cases - 34.06%). Expression of Ki-67 (p=0.009) and the presence of SIL (p=0.018) were associated to HPV infection. Expression of p53 (p=0.647) and bcl-2 (p=0.671) were not related to HPV status. The mean age of the patients was 53.2 years, without clear correlation between age group and HPV (p=0.095). The presence of HPV, especially type 18 in endocervical adenocarcinoma suggests that this agent can be an important cofactor in the development and progression of glandular neoplasms of the uterine cervix. The joint occurrence of endocervical adenocarcinoma and SIL may support this hypothesis. HPV may promote an increased proliferation index in endocervical adenocarcinoma, shown by the expression of Ki-67.
C1 [Cambruzzi, Eduardo] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Av. Loureiro da Silva, 1500/1308, B. Centro, 90050-240 Porto Alegre, Rio Grande do Sul, Brazil.
[Zettler, Galleano Claudio] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Av. Loureiro da Silva, 1500/1308, B. Centro, 90050-240 Porto Alegre, Rio Grande do Sul, Brazil.
[Alexandre, Osmar Pereira Claudio] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Av. Loureiro da Silva, 1500/1308, B. Centro, 90050-240 Porto Alegre, Rio Grande do Sul, Brazil.
RP Cambruzzi, E (reprint author), Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, 90050-240 Porto Alegre, Brazil.
EM dudacambruzzi@yahoo.com.br
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Riethford L, Riethford S, Lee KR: Human papillomaviruses, expression of p16, and early endocervical glandular neoplasia. Hum Pathol 33:899-904, 2002
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 114
EP 120
PG 7
ER
PT J
AU Culhaci, N
Meteoglu, I
Dundar, M
Kocak, I
AF Culhaci, Nil
Meteoglu, Ibrahim
Dundar, Mehmet
Kocak, Izzet
TI Histopathological Evaluation of Renal Vascular Changes in Rats Exposed to Passive Smoking
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE passive smoking; renal vasculature; rat
ID passive smoking; renal vasculature; rat
AB Cigarette smoking is an important risk factor for renal damage due to its effects on small interlobular arteries. We investigated the effects of long-term passive smoking on renal vascular structures in healthy rats exposed to smoke soon after birth. Forty-two Sprague-Dawley rats (21 males and 21 females) exposed to passive smoking comprised the experimental group and 33 non-exposed rats (17 males and 16 females) comprised the control group. The number of renal vessels, as well as the level of glomerular capillary sclerosis, hyalinosis of arterioles, and myointimal hyperplasia of arteries was assessed in renal biopsy specimens. The mean number of renal vessels in male and female rats exposed to passive smoke (21.71 and 13.81, respectively) did not significantly differ from the mean number of renal vessels in male and female control rats (22.47 and 13.06, respectively) (p>0.05). Levels of glomerulosclerosis, hyalinosis, and myointimal hyperplasia also did not differ between the experimental and control groups (p>0.05). Histopathologic evidence of renal vascular damage was not found in young rats exposed to passive smoke for 4 months. A longer or higher degree of exposure to cigarette smoke components may be required before such changes manifest, and aging and primary renal disease may play a role.
C1 [Culhaci, Nil] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Meteoglu, Ibrahim] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Dundar, Mehmet] Adnan Menderes University, Faculty of Medicine, Department of UrologyAydin, Turkey.
[Kocak, Izzet] Adnan Menderes University, Faculty of Medicine, Department of UrologyAydin, Turkey.
RP Culhaci, N (reprint author), Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
EM nculhaci@hotmail.com
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Odoni G, Ogata H, Viedt C, et al: Cigarette smoke condensate aggravates renal injury in the renal ablation model. Kidney Int 61: 2090-2098, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2005
VL 11
IS 2
BP 121
EP 124
PG 4
ER
PT J
AU Sapi, Z
Papai, Zs
Hruska, A
Antal, I
Bodo, M
Orosz, Zs
AF Sapi, Zoltan
Papai, Zsuzsa
Hruska, Anett
Antal, Imre
Bodo, Miklos
Orosz, Zsolt
TI Her-2 Oncogene Amplification, Chromosome 17 and DNA Ploidy Status in Synovial Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE synovial sarcoma; Her-2 oncogene; FISH; DNA ploidy; immunohistochemistry; prognostic factor
ID synovial sarcoma; Her-2 oncogene; FISH; DNA ploidy; immunohistochemistry; prognostic factor
AB The treatment options for synovial sarcoma (SS) are very limited, though this type of sarcoma seems to be more heterogeneous than it has been traditionally considered. The present study investigates the Her-2 oncogene status of 20 cases of SS, to determine whether Her-2 amplification can be considered as a prognostic factor. Her-2 oncogene amplification was determined on smears (frozen material was used from our tumor bank in each case), using fluorescence in situ hybridization technique (dual color FISH with centromeric probe for chromosome 17 and specific probe for Her-2 oncogene). Moreover, protein expression was assessed by immunohistochemistry, and DNA ploidy status was measured using image analysis. We had 5 biphasic and 15 monophasic SSs, patients’ age ranged from 13 to 68 years (mean, 39.8 years). Tumor size was larger than 5 cm in each case. Follow-up time ranged from 6 to 78 months (mean, 38.5 months). For statistical analysis the chi-square test was used. Her-2 oncogene amplification was found in three cases (15.0%) of 20 SSs. These cases proved to be 2+ positive by immunohistochemistry, but massive amplification, characteristic of a subset of breast carcinomas, was not observed. Her-2 oncogene amplification was significantly associated with a lower risk of developing metastasis (P<0.05) (none of the 3 amplified cases had metastases), while no association was found with recurrence. Six cases proved to be aneuploid and 14 were diploid, but no association was found between Her-2 amplification status and ploidy, and between ploidy status and metastasis or recurrence. Our results emphasize and confirm that Her-2 oncogene amplification is a rare event in SS, but the small subset of SS with Her-2 amplification has a better overall prognosis. Furthermore, this may open a theoretically new treatment possibility with Trastuzumab for Her-2-amplified cases of SS.
C1 [Sapi, Zoltan] St John's Hospital, Department of Pathology, Diosarok ut 1., H-1125 Budapest, Hungary.
[Papai, Zsuzsa] National Health Institute, Department of OncologyBudapest, Hungary.
[Hruska, Anett] Semmelweis University, Institute of Morphology and PhysiologyBudapest, Hungary.
[Antal, Imre] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Bodo, Miklos] St John's Hospital, Department of Pathology, Diosarok ut 1., H-1125 Budapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
RP Sapi, Z (reprint author), St John's Hospital, Department of Pathology, H-1125 Budapest, Hungary.
CR Bergh P, Meis-Kindblom JM, Gherlinzoni F, et al: Synovial sarcoma: identification of low and high risk groups. Cancer 85:2596-2607, 1999
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 133
EP 138
PG 6
ER
PT J
AU Nicolson, LG
AF Nicolson, L Garth
TI Lipid Replacement/Antioxidant Therapy as an Adjunct Supplement to Reduce the Adverse Effects of Cancer Therapy and Restore Mitochondrial Function
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lipids; antioxidants; cancer therapy; dietary supplement; fatigue; mitochondria
ID lipids; antioxidants; cancer therapy; dietary supplement; fatigue; mitochondria
AB The most common complaints of cancer patients undergoing chemo- or radiotherapy are fatigue, nausea, vomiting, malaise, diarrhea and headaches. These adverse effects are thought to be due to damage of normal tissues during the course of therapy. In addition, recent evidence indicates that fatigue is related to reduced mitochondrial function through loss of efficiency in the electron transport chain caused by membrane oxidation, and this occurs during aging, in fatiguing illnesses and in cancer patients during cytotoxic therapy. Lipid Replacement Therapy administered as a nutritional supplement with antioxidants can prevent oxidative membrane damage to normal tissues, restore mitochondrial and other cellular membrane functions and reduce the adverse effects of cancer therapy. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue by protecting mitochondrial and other cellular membranes from oxidative and other damage. In cancer patients a placebo-controlled, cross-over clinical trial using Lipid Replacement Therapy plus antioxidants demonstrated that the adverse effects of chemotherapy can be reduced in 57-70% of patients. Dietary use of unoxidized membrane lipids plus antioxidants is recommended for patients undergoing cancer therapy to improve quality of life but should not be taken at the same time of day as the therapy.
C1 [Nicolson, L Garth] The Institute for Molecular Medicine, Department of Molecular Pathology, 16371 Gothard St. H, CA 92647 Huntington Beach, California, USA.
RP Nicolson, LG (reprint author), The Institute for Molecular Medicine, CA 92647 Huntington Beach, USA.
EM gnicolson@immed.org
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Romanelli A, Bozzone A, Magrone G, et al: Cancer-related fatigue: evaluation and treatment. Rays 29: 453-455, 2004.
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Ahlberg K, Ekman T, Gaston-Johansson F: Fatigue, psychological distress, coping resources, and functional status during radiotherapy for uterine cancer. Oncol Nurs Forum 32: 633- 640, 2005.
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Nicolson GL: Lipid replacement as an adjunct to therapy for chronic fatigue, anti-aging and restoration of mitochondrial function. J Am Nutraceut Assoc 6: 22-28, 2003.
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Chen D, Cao G, Hastings T, et al: Age-dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria. J Neurochem 81: 1273-1284, 2002.
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Manuel y Keenoy B, Moorkens G, Vertommen J, et al: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci 68: 2037-2049, 2001.
Richards RS, Roberts TK, McGregor NR, et al: Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 5: 35-41, 2000.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 139
EP 144
PG 6
ER
PT J
AU Elek, G
Gyokeres, T
Schafer, E
Burai, M
Pinter, F
Pap,
AF Elek, Gabor
Gyokeres, Tibor
Schafer, Eszter
Burai, Maria
Pinter, Ferenc
Pap, Akos
TI Early Diagnosis of Pancreatobiliary Duct Malignancies by Brush Cytology and Biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE intraductal biopsy; intraductal cytology; pancreatobiliary strictures; sensitivity and specificity; sampling-; processing- and interpretive errors
ID intraductal biopsy; intraductal cytology; pancreatobiliary strictures; sensitivity and specificity; sampling-; processing- and interpretive errors
AB Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients’ clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and parapapillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria - primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.
C1 [Elek, Gabor] Central Railway Hospital and Polyclinic, Department of PathologyBudapest, Hungary.
[Gyokeres, Tibor] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky u. 111., H-1062 Budapest, Hungary.
[Schafer, Eszter] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky u. 111., H-1062 Budapest, Hungary.
[Burai, Maria] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky u. 111., H-1062 Budapest, Hungary.
[Pinter, Ferenc] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky u. 111., H-1062 Budapest, Hungary.
[Pap, Akos] Central Railway Hospital and Polyclinic, Department of Gastroenterology, Podmaniczky u. 111., H-1062 Budapest, Hungary.
RP Pap, (reprint author), Central Railway Hospital and Polyclinic, Department of Gastroenterology, H-1062 Budapest, Hungary.
EM papakos@kkk.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 145
EP 155
PG 11
ER
PT J
AU Behjati, F
Atri, M
Najmabadi, H
Nouri, K
Zamani, M
Mehdipour, P
AF Behjati, Farkhondeh
Atri, Morteza
Najmabadi, Hossein
Nouri, Keramat
Zamani, Mahdi
Mehdipour, Parvin
TI Prognostic Value of Chromosome 1 and 8 Copy Number in Invasive Ductal Breast Carcinoma among Iranian Women: An Interphase FISH Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; Iranian women; interphase FISH; clinicopathological parameters; chromosome 1 and 8 aneusomy; prognosis
ID breast cancer; Iranian women; interphase FISH; clinicopathological parameters; chromosome 1 and 8 aneusomy; prognosis
AB Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients’ age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.
C1 [Behjati, Farkhondeh] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
[Atri, Morteza] Cancer Institute, Faculty of Medicine, Tehran University of Medical Sciences, Department of SurgeryTehran, Iran.
[Najmabadi, Hossein] University of Social Welfare and Rehabilitation Sciences, Genetics Research CenterTehran, Iran.
[Nouri, Keramat] School of Public Health, Tehran University of Medical Sciences, Department of Epidemiology and BiostatisticsTehran, Iran.
[Zamani, Mahdi] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
[Mehdipour, Parvin] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
RP Mehdipour, P (reprint author), Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical Genetics, Tehran, Iran.
EM mehdipor@sina.tums.ac.ir
CR Adeyinka A, Mertens F, Idvall I, et al: Multiple polysomies in breast carcinoma: preferential gain of chromosomes 1, 5, 6, 7, 12, 16, 17, 18, and 19. Cancer Genet Cytogenet 111: 144-148, 1999.
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Jain AN, Chin K, Borresen- Dale AL, et al: Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with P53 status and patient survival. Proc Natl Acad Sci 98: 7952-7957, 2001.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 157
EP 163
PG 7
ER
PT J
AU Zalatnai, A
AF Zalatnai, Attila
TI P-glycoprotein Expression is Induced in Human Pancreatic Cancer Xenografts During Treatment with a Cell Cycle Regulator, Mimosine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE P-glycoprotein; pancreatic cancer; xenografts; human tumors; mimosine
ID P-glycoprotein; pancreatic cancer; xenografts; human tumors; mimosine
AB Application of several cell cycle checkpoint regulators seem to be promising in various experimental models including pancreatic cancer, and they are being evaluated in Phase I-II clinical trials. Among these compounds, mimosine, a plant-derived amino acid has shown an antineoplastic effect on human lung or pancreatic cancer xenografts in addition to cell cycle arrest in the late G1 phase. In the present study, immunosuppressed CBA mice bearing subcutaneously growing human ductal pancreatic adenocarcinomas were treated with 30 mg/kg L-mimosine for 34 days. The treatment resulted in retardation of tumor growth, accompanied by a significantly diminished proliferative activity (22.6% ± 1.7% Ki-67 positivity vs. 29.9% ± 1.1% in controls, mean ± SEM, P < 0.007) and an increased apoptotic rate (14.5 ± 1.1 apoptotic cells/mm2 vs. 3.8 ± 0.4/mm2 in the controls, P < 0.0001). The immunohistochemical expression of the multidrug resistance gene (MDR1)-encoded Pglycoprotein (p170) was studied. The parental and the untreated tumors did not express p170 protein, but in the mimosine-treated samples 30 to 60% of the carcinoma cells displayed a linear, membranebound positivity. The results indicate that P-glycoprotein is inducible by a cell cycle regulator, creating an acquired resistant phenotype.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
CR Abe S, Kubota T, Otani Y, et al: UCN-01, 7-hydroxystaurosporine, inhibits in vivo growth of human cancer cells through selective perturbation of G1 phase checkpoint machinery. Jpn J Cancer Res 92: 537-545, 2001.
Abolhoda A, Wilson AE, Ross H, et al: Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin Cancer Res 5: 3352-3356, 1999.
Bocsi J, Zalatnai A: Establishment and long term xenografting of human pancreatic carcinomas in immunosuppressed mice: Changes and stability in morphology, DNA ploidy and proliferative activity. J Cancer Res Clin Oncol 125: 9-19, 1999.
Buolamwini JK: Cell cycle molecular targets in novel anticancer drug discovery. Curr Pharm Des 6: 379-392, 2000.
Chang HC, Lee TH, Chuang LY, et al: Inhibitory effect of mimosine on proliferation of human lung cancer cells is mediated by multiple mechanisms. Cancer Lett 145: 1-8, 1999.
Chang HC, Weng CF, Yen MH, et al: Modulation of cell cycle regulatory protein expression and suppression of tumor growth by mimosine in nude mice. Int J Oncol 17: 659-665, 2000.
Chaudhary PM, Roninson IB: Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J Natl Cancer Inst 85: 632-639, 1993.
Chung HC, Rha SY, Kim JH, et al: P-glycoprotein: the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer. Breast Cancer Res Treat 42: 65-72, 1997.
Fardel O, Lecureur V, Daval S, et al: Up-regulation of P-glycoprotein expression in rat liver cells by acute doxorubicin treatment. Eur J Biochem 246: 186-192, 1997.
Feldman ST, Schonthal A: Negative regulation of histone H1 kinase expression by mimosine, a plant amino acid. Cancer Res 54: 494-498, 1994.
Goldstein LJ, Galski H, Fojo A, et al: Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81: 116-124, 1989.
Granzotto M, Drigo I, Candussio L, et al: Rifampicin and verapamil induce the expression of P-glycoprotein in vivo in Ehrlich ascites tumor cells. Cancer Lett 205: 107-115, 2004.
Jimenez RE, Zalupski MM, Frank JJ, et al: Multidrug resistance phenotype in high grade soft tissue sarcoma: correlation of P-glycoprotein immunohistochemistry with pathologic response to chemotherapy. Cancer 86: 976-981, 1999.
Krude T: Mimosine arrests proliferating human cells before onset of DNA replication in a dose-dependent manner. Exp Cell Res 247: 148-159, 1999.
Lage H, Dietel M: Multiple mechanisms confer different drugresistant phenotypes in pancreatic carcinoma cells. J Cancer Res Clin Oncol 128: 349-357, 2002.
Leonard GD, Fojo T, Bates SE: The role of ABC transporters in clinical practice. Oncologist 8: 411-424, 2003.
Licht T, Fiebig HH, Bross KJ, et al: Induction of multiple-drug resistance during anti-neoplastic chemotherapy in vitro. Int J Cancer 49: 630-637, 1991.
Lu Z, Kleeff J, Shrikhande S, et al: Expression of the multidrugresistance 1, MDR1, gene and prognosis in human pancreatic cancer. Pancreas 21: 240-247, 2000.
Mealey KL, Barhoumi R, Burghardt RC, et al: Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Antimicrob Agents Chemother 46: 755-761, 2002.
Monden N, Abe S, Hishikawa Y, et al: The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy. Int J Surg Invest 1: 3-10, 1999.
Nawrocki ST, Sweeney-Gotsch B, Takamori R, McConkey DJ: The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 3: 59-70, 2004.
Ng IO, Lam KY, Ng M, et al: Expression of P-glycoprotein, a multidrug-resistance gene product, is induced by radiotherapy in patients with oral squamous cell carcinoma. Cancer 83: 851- 857, 1998.
Nielsen D, Eriksen J, Maare C, et al. P-glycoprotein expression in Ehrlich ascites tumour cells after in vitro and in vivo selection with daunorubicin. Br J Cancer 78: 1175-1180, 1998.
Owa T, Yoshino H, Yoshimatsu K, Nagasu T: Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem 8: 1487-1503, 2001.
Ruiz van Haperen VW, Veerman G, Eriksson S, et al. Induction of resistance to 2’,2’-difluorodeoxycytidine in the human ovarian cancer cell line A2780. Semin Oncol 22(Suppl 11): 35-41, 1995.
Sandor V, Bakke S, Robey RW, et al: Phase I trial of the histone deacetylase inhibitor, depsipeptide, FR901228, NSC 630176), in patients with refractory neoplasms. Clin Cancer Res 8: 718- 728, 2002.
Sandor V, Robbins AR, Robey R, et al. FR901228 causes mitotic arrest but does not alter microtubule polymerization. Anticancer Drugs 11: 445-545, 2000.
Sato N, Ohta T, Kitagawa H, et al: FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells. Int J Oncol 24: 679-685, 2004.
Schondorf T, Neumann R, Benz C, et al: Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines. Recent Results Cancer Res 161: 111-116, 2003.
Sun D, Urrabaz R, Buzello C, Nguyen M: Induction of DNA ligase I by 1-beta-D-arabinosylcytosine and aphidicolin in Mia- PaCa human pancreatic cancer cells. Exp Cell Res 280: 90-96, 2002.
Suwa H, Ohshio G, Arao S, et al: Immunohistochemical localization of P-glycoprotein and expression of the multidrug resistance- 1 gene in human pancreatic cancer: relevance to indicator of better prognosis. Jpn J Cancer Res 87: 641-649, 1996.
Thomas H, Coley HM: Overcoming multidrug resistance in cancer: an update on clinical strategy on inhibiting P-glycoprotein. Cancer Control 10: 159-165, 2003.
Tomida A, Naito M, Tsuruo T: Acute induction of adriamycin-resistance in human colon carcinoma HT-29 cells exposed to a sublethal dose of adriamycin. Jpn J Cancer Res 86: 224-232, 1995.
Tsvetkov LM, Russev GC, Anachkova BB: Effect of mimosine on DNA synthesis in mammalian cells. Cancer Res 57: 2252- 2255, 1997.
Wada M, Hosotani R, Lee JU, et al: An exogenous cdk inhibitor, butyrolactone-I, induces apoptosis with increased Bax/Bcl2 ratio in p53-mutated pancreatic cancer cells. Anticancer Res 18: 2559-2566, 1998.
Wang G, Miskimins R, Miskimins WK: Mimosine arrests cells in G1 by enhancing the levels of p27(Kip1). Exp Cell Res 254: 64-71, 2000.
Wartenberg M, Fischer K, Hescheler J, Sauer H: Modulation of intrinsic P-glycoprotein expression in multicellular prostate tumor spheroids by cell cycle inhibitors. Biochim Biophys Acta 1589: 49-62, 2002.
Watson PA, Hanauske-Abel HH, Flint A, Lalande M: Mimosine reversibly arrests cell cycle progression at the G1-S phase border. Cytometry 12: 242-246, 1991.
Zalatnai A: Epidermal growth factor receptor, somatostatin and bcl-2 in human pancreatic tumor xenografts. An immunohistochemical study. Pathol Oncol Res 5: 146-151, 1999.
Zalatnai A: Potential role of cell cycle synchronizing agents in combination treatment modalities of malignant tumors. In vivo 19: 85-91, 2005.
Zalatnai A, Bocsi J: Mimosine, a plant-derived amino acid induces apoptosis in human pancreatic cancer xenografts. Anticancer Res 23: 4007-4010, 2003.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 164
EP 169
PG 6
ER
PT J
AU Dundar, M
Kocak, I
Culhaci, N
Erol, H
AF Dundar, Mehmet
Kocak, Izzet
Culhaci, Nil
Erol, Haluk
TI Determination of Apoptosis Through Bax Expression in Cryptorchid Testis: an Experimental Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bax; spermatogonia; spermatocyte; undescended testis
ID Bax; spermatogonia; spermatocyte; undescended testis
AB The aim was to determine the expression of Bax in germ cells of rats with unilateral experimental cryptorchidism, and to evaluate the role of apoptosis in germ cell loss. Twenty-one prepubertal rats were randomly subdivided into three groups after the execution of the left cryptorchidism model. Group 1 (n=8), group 2 (n=6) and group 3 (n=7) rats were killed at the end of the first, second and third month, respectively. Bax expression was assessed in Sertoli cells, spermatogonia and spermatocytes by immunohistochemistry. Percentages of Bax expression in spermatocytes and spermatogonia were decreased in the left testicles in the 2nd and 3rd months compared to results obtained in the 1st month (p<0.05). Percentage of Bax expression in the left testicles of group 1, at the level of both spermatogonia and spermatocytes was higher than that in the right one (p<0.05). However, in groups 2 and 3, the higher Bax expression on the left side was only seen in the spermatocytes (p<0.05). In all groups, the mean weight of the left testicle was lower than that of the scrotal counterpart where the difference was significant only in groups 1 and 3 (p<0.05). The weight of the left and right testicles was increasing with time. In this model of cryptorchidism, the affected testis had a decreased weight compared to the normal one. Based on the increased Bax expression, we think that apoptosis may play a role in the germ cell loss.
C1 [Dundar, Mehmet] Adnan Menderes University, Faculty of Medicine, Department of Urology, 09100 Aydin, Turkey.
[Kocak, Izzet] Adnan Menderes University, Faculty of Medicine, Department of Urology, 09100 Aydin, Turkey.
[Culhaci, Nil] Adnan Menderes University, Medical Faculty, Pathology DepartmentAydin, Turkey.
[Erol, Haluk] Adnan Menderes University, Faculty of Medicine, Department of Urology, 09100 Aydin, Turkey.
RP Dundar, M (reprint author), Adnan Menderes University, Faculty of Medicine, Department of Urology, 09100 Aydin, Turkey.
EM medundar2002@yahoo.com
CR Heiskanen P, Billig H, Toppari J, et al: Apoptotic cell death in the normal and cryptorchid human testis: The effect of human chorionic gonadotropin on testicular cell survival. Pediatr Res 40: 351-356, 1996
Shikone T, Billig H, Hsueh JW: Experimentally induced cryptorchidism increases apoptosis in rat testis. Biol Reprod 51: 865-872, 1994
Hikim AP, Lue Y, Yamamoto CM, et al: Key apoptotic pathways for heat-induced programmed germ cell death in the testis. Endocrinology 144: 3167-3175, 2003
Hikim AP, Lue Y, Diaz-Romero M, et al: Deciphering the pathways of germ cell apoptosis in the testis. J Steroid Biochem Mol Biol 85: 175- 182, 2003
Damavandi E, Hishikawa Y, Izumi S, et al: Involvement of Bax redistribution in the induction of germ cell apoptosis in neonatal mouse testes. Acta Histochem Cytochem 35: 449-459, 2002
Miura M, Sashagawa I, Suzuki Y, et al: Apoptosis and expression of apoptosis-related genes in the mouse testis following heat exposure. Fertil Steril 77: 787-793, 2002
Zini A, Abitbol J, Schulsinger D, et al: Restoration of spermatogenesis after scrotal replacement of experimentally cryptorchid rat testis. Assessment of germ cell apoptosis and eNOS expression. Urology 53: 223-227, 1999
Knudson CM, Tung KS, Tourtellote WG, et al: Bax deficient mice with lymphoid hyperplasia and male germ cell death. Science 270: 96-99, 1995
Dundar M, Kocak I, Culhaci N: A new experimental model for cryptorchidism: inguinoscrotal approach. Urol Res 29: 178-181, 2001
Hellstrom WJG, Monga M: Cryptorchidism and infertility. Male Infertility and Sexual Dysfunction., Ed: Hellstrom WJG), Springer, 1997, pp 307-322
Billig H, Furuta I, Rivier C, et al: Apoptosis in testis germ cells: developmental changes in gonadotropin dependence and localization to selective tubule stages. Endocrinology 136: 5-12, 1995
Majno G, Joris I: Apoptosis, oncosis and necrosis. An overview of cell death. Am J Pathol 146: 3-15, 1995
Tomomasa H, Adachi Y, Oshio S, et al: Germ cell apoptosis in undescended testis. The origin of its impaired spermatogenesis in the TS inbred rat. J Urol 168: 343-347, 2002
Ogi S, Tanji N, Yokoyama M, et al: Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism. Urol Res 26: 17-21, 1998
Wang ZQ, Todani T, Watanabe A, et al: Germ cell degeneration in experimental unilateral cryptorchidism: role of apoptosis. Pediatr Surg Int 14: 9-13, 1998
Yan W, Samson M, Jegou B, Toppari J: Bcl-w forms complexes with Bax and Bak, and elevated ratios of Bax/Bcl-w and Bak/Bcl-w correspond to spermatogonial and spermatocyte apoptosis in the testis. Mol Endocrinol 14: 682-699, 2000
Xu J, Xu Z, Jiang Y, et al: Cryptorchidism induces mouse testicular germ cell apoptosis and changes in bcl-2 and Bax protein expression. J Environ Pathol Toxicol Oncol 19: 25-33, 2000
Ito K, Tanemura K, Gotoh H, et al: Apoptosis-like cell death in experimentally- induced cryptorchidism in adult mice. J Vet Med Sci 59: 353-359, 1997
Wang QZ, Watanabe Y, Toki A, et al: Altered distribution of Sertoli cell vimentin and increased apoptosis in cryptorchid rats. J Pediatr Surg 37: 648-652, 2002
Ohta Y, Nishikawa A, Fukazawa Y, et al: Apoptosis in adult mouse testis induced by experimental cryptorchidism. Acta Anat 157: 195- 204, 1996.
Barqawi A, Trummer H, Meacham R: Effect of prolonged cryptorchidism on germ cell apoptosis and testicular sperm count. Asian J Androl 6: 47-51, 2004
Kocak I, Dundar M, Hekimgil M, et al: Assessment of germ cell apoptosis on cryptorchid rats. Asian J Androl 4: 183-186, 2002
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 170
EP 173
PG 4
ER
PT J
AU Vari, S
Cserneky, M
Kadar, A
Szende, B
AF Vari, Sandor
Cserneky, Maria
Kadar, Anna
Szende, Bela
TI Development of Present and Future of Telepathology in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE telepathology; consultations; diagnosis; database
ID telepathology; consultations; diagnosis; database
AB Pathologists in Hungary evaluate several hundred thousand histological specimens yearly, and a second opinion is requested in 5-10 percent of cases. Application of multimedia systems (i.e. telepathology) is convenient and efficient to establish a correct diagnosis in such cases. The first telepathology connection in Hungary has been established between the 1st Department of Pathology and Experimental Cancer Research, Semmelweis University and the Department of Pathology, Central Hospital of the Ministry of the Interior. Further development occurred in the course of various projects, supported by the EU (Interpath, Retransplant, BePro): new stations were established in three university institutes and six county hospitals. Electronic fixation of the images and their transmission by telephone line (ISDN) is easily available and an important feature of the multimedia system applied in telepathology. The system used by us is suited to evaluate frozen or paraffin-embedded histologic sections, as well as immunohistochemical and cytologic specimens, if necessary supplemented with transmission of macroscopic pictures. Our experience with bilateral consultations has proven the importance of telepathology. The telepathology system established in Hungary is now ready to join the telepathology network of the EU.
C1 [Vari, Sandor] Varimed LtdBudapest, Hungary.
[Cserneky, Maria] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Kadar, Anna] International Academy of Pathology, Hungarian DivisionBudapest, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Fischer SI, Nandedkar MA, Williams BH, Abbondanzo L: Telepathology in a clinical consultative practice. Hum Pathol 32: 1327-1333, 2001
Allen EA, Ollayos CW, Tellado MV, et al: Characteristics of a telecytology consultation service. Hum Pathol 32: 1323-1326, 2001
Weinstein RS, Descour MR, Lian C, et al: Telepathology overview: From concept to implementation. Hum Pathol 23: 1283-1299, 2001
Kayser K, Fritz P, Drlicek M: Aspects of telepathology in routinary diagnostic work with specific emphasis on ISDN. Arch Anat Cytol Pathol 43: 216-218, 1995
Schwarzmann P, Schmid J, Schnorr C, et al: Telemicroscopy stations for telepathology based on broadband and ISDN connections. Arch Anat Cytol Pathol 43: 209-215, 1995
Gombas P, Szende B, Stotz G: Telecommunicative support of decision in diagnostic pathology. Experiences with the first Hungarian telepathology system, in Hungarian). Orvosi Hetilap 137: 2299-2303, 1996
Otto S, Kasler M: Cancer mortality and incidence in Hungary, related to European data, in Hungarian). Magyar Onkologia 46: 111-117, 2002
Molnar B, Berczi L, Diczhazy C, et al: Digital slide and virtual microscopy based routine and telepathology evaluation of routine gastrointestinal biopsy specimens. J Clin Pathol 56: 1-6, 2003
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 174
EP 177
PG 4
ER
PT J
AU Venizelos, I
Tamiolakis, D
Lambropoulou, M
Nikolaidou, S
Bolioti, S
Papadopoulos, H
Papadopoulos, N
AF Venizelos, Ioannis
Tamiolakis, Demetrio
Lambropoulou, Maria
Nikolaidou, Sylva
Bolioti, Sophia
Papadopoulos, Hlias
Papadopoulos, Nikolas
TI An Unusual Case of Posttransplant Peritoneal Primary Effusion Lymphoma with T-cell Phenotype in a HIV-negative Female, not Associated with HHV-8
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE primary effusion lymphoma; non-Hodgkin’s lymphoma; immunohistochemistry
ID primary effusion lymphoma; non-Hodgkin’s lymphoma; immunohistochemistry
AB Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin’s lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/µL). Occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. From a pathogenetic point of view, PEL has been related to Kaposi’s sarcoma associated herpes virus (also named human herpesvirus 8, HHV-8), an etiological factor of Kaposi’s sarcoma. The relative infrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome support the need of a deeper knowledge. We present here the clinical-biological findings of a patient, HIVseronegative, who was diagnosed with peritoneal PEL of T-cell origin, and not HHV-8-associated, five years after renal transplantation.
C1 [Venizelos, Ioannis] Ippokratio General Hospital of Salonica, Department of PathologySalonica, Greece.
[Tamiolakis, Demetrio] General Hospital of Chania, Department of CytologyChania, Greece.
[Lambropoulou, Maria] Democritus University of Thrace, Department of Histology-Embryology, Dragana, 68100 Alexandroupolis, Greece.
[Nikolaidou, Sylva] General Hospital of Chania, Department of CytologyChania, Greece.
[Bolioti, Sophia] General Hospital of Chania, Department of CytologyChania, Greece.
[Papadopoulos, Hlias] Democritus University of Thrace, Department of Histology-Embryology, Dragana, 68100 Alexandroupolis, Greece.
[Papadopoulos, Nikolas] Democritus University of Thrace, Department of Histology-Embryology, Dragana, 68100 Alexandroupolis, Greece.
RP Papadopoulos, N (reprint author), Democritus University of Thrace, Department of Histology-Embryology, 68100 Alexandroupolis, Greece.
EM npapad@med.duth.gr
CR Carbone A, Cilia AM, Gloghini A, et al: Primary effusion lymphoma cell lines harbouring human herpesvirus type 8. Leuk Lymphoma 36: 447-456, 2000.
Fassone L, Bhatia K, Gotierrez M, et al: Molecular profile of Epstein-Barr virus infection in HHV-8-positive primary effusion lymphoma. Leukemia 14: 271-277, 2000.
Ascoli V, Scalzo CC, Danese C, et al: Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men. Eur Respir J 14: 1231-1234, 1999.
Chang Y, Cesarman E, Pessin MS, et al: Identification of herpesvirus- like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865-1869, 1994
Frank D, Cesarman E, Liu YF, et al: Post-transplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus. Blood 85: 1396-1403, 1995.
Gaidano G, Ballerini P, Gong JZ, et al: p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci USA 88: 5423-5417, 1991.
Ohshima K, Ishiguro M, Yamasaki S, et al: Chromosomal and comparative genomic analyses of HHV-8-negative PEL in 5 HIVnegative Japanese patients. Leuk Lymphoma 43: 595-601, 2002
Shimazaki M, Fujita M, Tsukamoto K, et al: An unusual case of PEL in a HIV-negative patient not pathogenetically associated with HHV-8. Eur J Haematol 71: 62-67, 2003.
Said JW, Shintaku IP, Asou H, et al: Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype. Arch Pathol Lab Med 123: 257-260, 1999
Kinney MC, Kadin ME. The pathologic and clinical spectrum of anaplastic large cell lymphoma and correlation with ALK gene dysregulation. Am J Clin Pathol. 1999;111, suppl 1): S56- S67.
Chan AC, Chan JK, Yan KW, Kwong YL: Anaplastic large cell lymphoma presenting as a pleural effusion and mimicking primary effusion lymphoma. A report of two cases. Acta Cytol 47: 809-816, 2003.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 178
EP 181
PG 4
ER
PT J
AU Aydin, MV
Cekinmez, M
Kizilkilic, O
Kayaselcuk, F
Sen, O
Altinors, N
AF Aydin, M Volkan
Cekinmez, Melih
Kizilkilic, Osman
Kayaselcuk, Fazilet
Sen, Orhan
Altinors, Nur
TI Unusual Case of Skull Metastasis Secondary to Pancreatic Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adenocarcinoma; metastasis; pancreas; skull
ID adenocarcinoma; metastasis; pancreas; skull
AB Skull metastasis must be kept in mind when considering the differential diagnosis of a skull tumor. Skull metastases cause local swelling that is usually painless, and rarely they lead to neurologic dysfunction. Despite the fact that hematogenous skull metastases can be caused by nearly all types of tumors (lung, prostate, thyroid carcinoma, malignant melanoma), breast cancer is associated with the highest rate of metastatic skull lesions. We report an extremely rare case of skull metastasis from a pancreatic adenocarcinoma, in a 65-year-old woman, presented with painless frontoparietal scalp swelling which developed within three months. To the best of our knowledge, this is the second case involving the skull secondary to a pancreatic adenocarcinoma, and the first case when skull metastasis was the first evidence of a pancreatic adenocarcinoma.
C1 [Aydin, M Volkan] Baskent University, Departments of Neurosurgery, Yuregir, 1250 Adana, Turkey.
[Cekinmez, Melih] Baskent University, Departments of Neurosurgery, Yuregir, 1250 Adana, Turkey.
[Kizilkilic, Osman] Baskent University, Department of RadiologyAdana, Turkey.
[Kayaselcuk, Fazilet] Baskent University, Department of PathologyAdana, Turkey.
[Sen, Orhan] Baskent University, Departments of Neurosurgery, Yuregir, 1250 Adana, Turkey.
[Altinors, Nur] Baskent University, Departments of Neurosurgery, Yuregir, 1250 Adana, Turkey.
RP Aydin, MV (reprint author), Baskent University, Departments of Neurosurgery, 1250 Adana, Turkey.
EM volkan8@hotmail.com
CR Bontoux D, Plazanet F, Azais I: Distribution of bone metastases of cancers. A scintigraphic study of 376 cases. Bull Acad Natl Med 182: 997- 1008, 1998
Constans JP, Donzelli R: Surgical features of cranial metastases. Surg Neurol 15: 35-38, 1981
Galicich JH, Arbit E, Wronski M: Metastatic brain tumors. In: Neurosurgery., Eds: Wilkins RH, Rengarachary SS), Vol 1, 2nd ed, New York, McGraw-Hill, 1996, pp 807-821
Gloria-Cruz TI, Schachern PA, Paparella MM, et al: Metastases to temporal bones from primary nonsystemic malignant neoplasms. Arch Otolaryngol Head Neck Surg 6: 209-214, 2000
Hornig K: Extensive osteolytic calotte destructions in primary breast cancer. Radiologe 28: 132-133, 1988
Igarashi M, Card GG, Johnson PE, Alford BR: Bilateral sudden hearing loss and metastatic pancreatic adenocarcinoma. Arch Otolaryngol 105: 196-199, 1979
Michael JB, Gokaslan ZL, DeMonte F, et al: Surgical resection of calvarial metastases overlying dural sinuses. Neurosurgery 48: 745-755, 2001
Stark AM, Eichmann T, Mehdorn HM: Skull metastases: clinical features, differential diagnosis, and review of the literature. Surg Neurol 60: 219-226, 2003
Wong GKC, Boet R, Poon WS, Ng HK: Lytic skull metastasis secondary to thyroid carcinoma in an adolescent. HKMJ 8: 149-151, 2002
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 182
EP 183
PG 2
ER
PT J
AU Terracciano, L
Bouygue, RG
Startari, R
Guerriero, F
Bouygue, MC
AF Terracciano, Luigi
Bouygue, R Gabriel
Startari, Rosario
Guerriero, Francesca
Bouygue, MR Colette
TI A Case of Fulminant ''Talc Pneumoconiosis”: Where is the Smoking Gun?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
C1 [Terracciano, Luigi] University of Milan Medical School, Melloni Paediatria, 52 Via Melloni, 20129 Milan, Italy.
[Bouygue, R Gabriel] University of Milan Medical School, Melloni Paediatria, 52 Via Melloni, 20129 Milan, Italy.
[Startari, Rosario] University of Milan Medical School, Melloni Paediatria, 52 Via Melloni, 20129 Milan, Italy.
[Guerriero, Francesca] University of Milan Medical School, Melloni Paediatria, 52 Via Melloni, 20129 Milan, Italy.
[Bouygue, MR Colette] University of Milan Medical School, Melloni Paediatria, 52 Via Melloni, 20129 Milan, Italy.
RP Terracciano, L (reprint author), University of Milan Medical School, Melloni Paediatria, 20129 Milan, Italy.
CR Dekel Y, Rath-Wolfson L, Rudniki Carlos, Koren R. Talc inhalation is a life-threatening condition. Path Oncol Res 10:231-233, 2004
Deer WA, Howie RA, Zussman J: Rock-Forming Minerals, vol III: Sheet Silicates. London, 1963, Longmans
Awai K, Yamane K, Nishioka Y, et al: Analysis of pyrophillitosis by highresolution computed tomography. Nippon Igaku Hosahsen Gakkai Zasshi 51: 656-662, 1991
Kurahashi M, Mizutani J, Hioki A: Determination of trace elements in sediment reference materials by monochromatic X-ray excitation X-ray fluorescence spectrometry. Anal Sci 21: 827-832, 2005
Karik AB: Immune response to exposure to occupational and environmental agents. ICMR Bulletin 31: 73-79, 2001
Miller A, Teirstein AS, Bader ME, et al: Talc pneumoconiosis. Significance of sublight microscopic mineral particles. Am J Med 50: 395-402, 1971
Fine LJ, Peters JM, Burgess WA, Di Berardinis LJ: Studies of respiratory morbidity in rubber workers. Part IV. Respiratory morbidity in talc workers. Arch Environ Health 31: 195-200, 1976
Accessed from: http://minerals.usgs.gov/minerals/pubs/commodity/ talc
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 184
EP 184
PG 1
ER
PT J
AU Koren, R
AF Koren, Rumelia
TI Reply
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
C1 [Koren, Rumelia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Pathology, Ramat AvivTel Aviv, Israel.
RP Koren, R (reprint author), Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Pathology, Tel Aviv, Israel.
CR Dimopoulos G, Piagnerelli M, Berre J, et al: Post mortem examination in the intensive care unit: still useful? Intensive Care Med 30: 2080-2085, 2004
Scancarello G, Romeo R, Sartorelli E: Respiratory disease as a result of talc inhalation. J Occup Environ Med 38: 610-614, 1996
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 185
EP 185
PG 1
ER
PT J
AU Nagy, Zs
AF Nagy, Zsuzsanna
TI Zoledronic acid (ZOMETA): a Significant Improvement in the Treatment of Bone Metastases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
C1 [Nagy, Zsuzsanna] St. Imre Hospital, Department Clinical Oncology, Tetenyi u. 12-16, H-1115 Budapest, Hungary.
RP Nagy, Zs (reprint author), St. Imre Hospital, Department Clinical Oncology, H-1115 Budapest, Hungary.
CR Coleman RE: Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27: 165- 176, 2001
Russell RG, Rogers MJ: Bisphosphonates: From the laboratory to the clinic and back again. Bone 25: 97-106, 1999
Hurst M, Noble S: Clodronate: A review of its use in breast cancer. Drugs Aging 15: 143-167, 1999
Theriault RL, Lipton A, Hortobagyi GN, et al: Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: A randomized, placebo-controlled trial – Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 17: 846-854, 1999
Gordon D, Rosen L, Coleman RE, et al: Long-term efficacy and safety of zoledronic acid compared with pamidronate in treatment of skeletal complications in patients with advanced multiple myeloma of breast cancer, Proc Am Soc Clin Oncol 22: 47, 2003, abstr 188)
Perry CM, Figgitt DP: Zoledronic acid: A review of its use in patients with advanced cancer. Drugs 64: 1197-1211, 2004
Kohno N, Aogi K, Minami H, et al: Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 23: 3314- 3321, 2005
Seneratne SG, Colston KW: Direct effects of bisphosphonates on breast cancer cells. Breast Cancer Res 4: 18-23, 2002
Powles T, McCloskey E, Kurkilahti M: Oral clodronate for adjuvant treatment of operable breast cancer: results of a randomized, double-blind, placebo-controlled multicenter trial. Proc Am Soc Clin Oncol 23: 9, 2004, abstr 528)
Jaschke A, Bastert G, Solomayer EF, et al: Adjuvant clodronate treatment improves the overall survival of primary breast cancer patients with micrometastases to bone marrow – a longtime follow-up. Proc Am Soc Clin Oncol 23: 9, 2004, abstr 529)
Coleman R, Gralow J, Bell R, Lipton A: Zoledronic acid is being investigated for the prevention of bone metastases in patients with early stage cancer. 7th workshop on Bisphosphonates, 24-26 March 2004, Davos, Switzerland, abstr 60)
Brufsky A, Harker GW, Beck J, et al: Zoledronic acid for prevention of cancer treatment induced bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: preliminary results of the Z-FAST trial. 27th Annual San Antonio Breast Cancer Symposium 2004, San Antonio, abstr 1114)
Brufsky A, Harker W, Beck J, et al: Zoledronic acid, ZA, effectively inhibits cancer treatment-induced bone loss, CTIBL, in postmenopausal women, PMW, with early breast cancer, BCa, receiving adjuvant Letrozole, Let): 12 mos BMD results of the FAST trial. ASCO Annual Meeting, Orlando, 2005, abstr 533)
Botteman MF, Aapro MS, Hay JW, et al: Cost effectiveness of intravenous, IV, zoledronic acid vs other IV bisphosphonates for the prevention of bone complications in breast cancer patients with bone metastases: A Markov model from the UK perspective. ASCO Annual Meeting, Orlando, 2005, abstr 721)
Body J, Lichinitser M, Tjulandin S, et al: Effect of oral ibandronate versus intravenous, i.v., zoledronic acid on markers of bone resorption with breast cancer and bone metastases: Results from a comparative phase III trial. ASCO Annual Meeting, Orlando, 2005, abstr 534)
Lipton A, Hei Y, Coleman R, et al: Suppression of bone turnover markers by zoledronic acid and correlation with clinical outcome. ASCO Annual Meeting, Orlando, 2005, abstr 532)
Jung J, Hwang G, Lee Y, et al: Pamidronate as adjuvant treatment for prevention of bone metastasis in breast cancer. ASCO Annual Meeting, Orlando, 2005, abstr 888)
Hortobagyi GN: Progress in the management of bone metastases: One continent at a time? J Clin Oncol 23, 1-3, 2005
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2005
VL 11
IS 3
BP 186
EP 186
PG 1
ER
PT J
AU Kopper, L
Timar, J
AF Kopper, Laszlo
Timar, Jozsef
TI Genomics of Prostate Cancer: Is There Anything to ''Translate''?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE prostate cancer; progression; genomics; proteomics
ID prostate cancer; progression; genomics; proteomics
AB This review provides an up-dated collection of data concerning the genetic and epigenetic changes during development, growth and progression of prostate cancer. Hereditary and susceptibility factors have a long list, similarly to the expression of single genes connected to various cell functions. It was a hope that covering a large set of genes, array technologies would clarify very rapidly the role of genetics in malignant diseases, offering targets for molecular diagnostics and therapy. The power of high-throughput techniques for the detection and global analysis of gene expression is unquestionable, interesting, astonishing as well as puzzling data have already been obtained. However, the standardization of the procedures is still missing and the reproducibility is rather low in many instances. Moreover, the different array methods can select different gene expression profiles, which makes the decision rather difficult. Another important question is, coming again from the array technologies, how far the genotype (the gene profiles or fingerprints) can reflect the actual phenotype in a highly complex and readily changing disease as cancer. Proteomics will provide a closer look to this seemingly unanswerable problem. We are at the beginning of the exploration of the behavior of cancer cells in order to apply a more effective therapy based on a more reliable set of diagnostic and prognostic informations.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 78., H-1085 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor ProgressionBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 197
EP 203
PG 7
ER
PT J
AU Mehes, G
AF Mehes, Gabor
TI Chromosome Abnormalities with Prognostic Impact in B-cell Chronic Lymphocytic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE CLL; chromsomal deletions; IgVH; prognosis
ID CLL; chromsomal deletions; IgVH; prognosis
AB The detailed analysis of the biologic features led to a rapid increase in clinically relevant information in CLL. The recognition of the prognostic role of IgVH hypermutation status and related phenotypic changes (CD38, ZAP-70 expression) as well as of chromosome abnormalities defined by cytogenetic analysis enabled a refined classification of the disease. Improvements in karyotyping and the introduction of fluorescence in situ hybridization (FISH) in routine hematological diagnostics raised the detection rate of chromosomal aberrations to approx. 60-80% in CLL. Among them, deletions of 17p and 11q have been associated with unfavorable prognosis. The deletion of the p53 locus (17p13) was described as the strongest independent predictor for aggressive behavior, resistance to chemotherapy and early death. On the contrary, an isolated deletion at 13q14 or a normal karyotype was related with a long survival. Classical and molecular cytogenetic analysis became an important tool for individual risk estimation. Unlike any other approaches, cytogenetic monitoring reflects the genetic heterogeneity and clonal growth dynamics during the course of the disease.
C1 [Mehes, Gabor] University of Pecs, Department of Pathology, Szigeti ut 12., H-7602 Pecs, Hungary.
RP Mehes, G (reprint author), University of Pecs, Department of Pathology, H-7602 Pecs, Hungary.
EM gabor.mehes@freemail.hu
CR Bacher U, Kern W, Schoch C, et al: Discrimination of chronic lymphocytic leukemia, CLL, and CLL/PL by cytomorphology can clearly be correlated to specific genetic markers as investigated by interphase fluorescence in situ hybridization, FISH). Ann Hematol 83: 349-355, 2004.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 205
EP 210
PG 6
ER
PT J
AU Naghibalhossaini, F
Pakdel, A
Ghaderi, AA
Saberi Firoozi, M
AF Naghibalhossaini, Fakhraddin
Pakdel, Abbas
Ghaderi, Ali Abbas
Saberi Firoozi, Mehdi
TI Effective Production of Carcinoembryonic Antigen by Conversion of the Membrane-bound Into a Recombinant Secretory Protein by Site-specific Mutagenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CEA; GPI; site-specific mutagenesis; immunotherapy
ID CEA; GPI; site-specific mutagenesis; immunotherapy
AB Carcinoembryonic antigen (CEA), the most widely used human tumor marker, is a heavily glycosylated protein over-expressed by a wide range of tumors. It has been indicated that CEA might be a useful target for human anti-tumor immunotherapy. CEA assay for research as well as clinical trials demands a continuous source of CEA protein preparations. In a multi-purpose research program to provide a reliable source for large production of CEA, we converted the membrane-bound carcinoembryonic antigen into a secretory protein by site-specific mutagenesis. We made the secretory CEA protein by introducing a new stop codon at 99 bp upstream of the original stop codon in CEA cDNA by PCR-based mutagenesis. The glycosylation of recombinant CEA proteins, especially those destined for administration to human trials is crucially important. To produce CEA with the same glycosylation pattern and immunogenicity as the native CEA expressed by human tumors in vivo, the truncated CEA cDNA which does not encode the last C-terminal 33-amino acid hydrophobic domain was transfected into HT29, a human colon carcinoma cell line by the calcium phosphate method. Stable transfectants were selected and pooled. CEA secretion from the cells was verified by analysis of the transfectant culture supernatant for CEA protein. As determined by ELISA, 16 µg/L of recombinant CEA was secreted per 106 transfectants within 48 hrs, an increase over 40 times relative to the untransfected cells. The size of the recombinant CEA secreted by HT29 transfectants in our experiment is identical to that of reference CEA secreted from tumors and is fully antigenic. It seems that the C-terminal truncation does not affect CEA glycosylation in HT29 cells. It is predicted that human cancer immunotherapy using recombinant CEA expressed in this system would be more effective than the commercial protein which is usually prepared from bacterial or other heterologous expression systems.
C1 [Naghibalhossaini, Fakhraddin] Shiraz University of Medical Sciences, Department of Biochemistry, P.O. Box 1167, 71345 Shiraz, Iran.
[Pakdel, Abbas] Shiraz University of Medical Sciences, Department of Biochemistry, P.O. Box 1167, 71345 Shiraz, Iran.
[Ghaderi, Ali Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Saberi Firoozi, Mehdi] Shiraz University of Medical Sciences, Gastroenterohepatology Research CenterShiraz, Iran.
RP Naghibalhossaini, F (reprint author), Shiraz University of Medical Sciences, Department of Biochemistry, 71345 Shiraz, Iran.
EM fakhraddin.naghibalhossaini@elf.mcgill.ca
CR Benchimol S, Fuks A, Jothy S, et al: Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57: 327-334, 1989.
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Hefta LJ, Schrewe H, Thompson JA, et al: Expression of complementary DNA and genomic clones for carcinoembryonic antigen and nonspecific cross-reacting antigen in Chinese hamster ovary and mouse fibroblast cells and characterization of the membrane-expressed products. Cancer Res 50: 2397-2403, 1990.
Hefta SA, Hefta LJ, Lee TD, et al: Carcinoembryonic antigen is anchored to membranes by covalent attachment to a glycosylphosphatidylinositol moiety: identification of the ethanolamine linkage site. Proc Natl Acad Sci USA 85: 4648-4652, 1988.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 211
EP 217
PG 7
ER
PT J
AU Raso, E
Tovari, J
Ladanyi, A
Varga, N
Timar, J
AF Raso, Erzsebet
Tovari, Jozsef
Ladanyi, Andrea
Varga, Norbert
Timar, Jozsef
TI Ligand-Mimetic Anti-αIIbβ3 Antibody PAC-1 Inhibits Tyrosine Signaling, Proliferation and Lung Colonization of Melanoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ?IIbß3; integrin; ligand-mimetic; melanoma
ID ?IIbß3; integrin; ligand-mimetic; melanoma
AB β3 integrin expression is the hallmark of melanoma and may serve as a potential therapeutic target. While αvβ3 integrin expression seems to be constitutive in melanoma, ectopic expression of platelet-αIIbβ3 is dependent on progression. B16a murine melanoma is a suitable model for studies on αIIbβ3 treatment strategies since αvβ3 is not expressed in this cell line. Here we have used a ligand-mimetic anti-αIIbβ3 monoclonal antibody, PAC-1, to test the biological consequences of αIIbβ3 modulation in melanoma cells. We have previously reported that in B16a cells FAK is constitutively active and tyrosine-phosphorylated. Upon PAC-1 binding to the surface αIIbβ3, which is in the active conformation, FAK became dephosphorylated through a process of PKC-dependent phosphatase activation. Furthermore, PAC-1 binding to B16a cells induced a significant decrease in phosphotyrosine-positive melanoma cells within 30 min. Treatment of B16a cells in vitro with PAC-1 significantly inhibited proliferation by decreasing the mitotic index but not affecting apoptotic rate. Incubation of B16a cells with PAC-1 decreased their lung colonization potential, suggesting a profound alteration in their biological behavior under the effect of this antibody. These preclinical data suggest that the ectopic expression of αIIbβ3 in melanoma cells can be exploited as a novel target of antibody therapy of melanoma.
C1 [Raso, Erzsebet] National Institute of Oncology, Department of Tumor Progression, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Tovari, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Ladanyi, Andrea] National Institute of Oncology, Department of Tumor Progression, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Varga, Norbert] National Institute of Oncology, Department of Tumor Progression, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
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Guo W and Giancotti FG: Integrin signaling during tumour progression. Nat Rev Mol Cell Biol 5: 816-826, 2004
Goel HL and Languino LR: Integrin signaling in cancer. Cancer Treat Res 119: 15-31, 2004
Kuphal S, Bauer R and Rosserhoff AK: Integrin signaling in malignant melanoma. Cancer Metast Rev 24:195-222, 2005
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Puerschel WC, Gawaz M, Worret W-I and Ring J: Immunoreactivity of glycoprotein IIb is present in metastasized but not in nonmetastasized primary malignant melanoma. Br J Dermatol 135: 883-887, 1996
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Trikha M, Timar J, Zacharek A, et al: Role for β3 integrins in human melanoma growth and survival. Int J Cancer 101: 156-167, 2002
Timar J, Trikha M, Szekeres K, et al: Expression and function of the high affinity αIIbβ3 integrin in murine melanoma cells. Clin Exp Metast 16: 437-455, 1998
Raso E, Tovari J, Toth K, et al: Ectopic αIIbβ3 integrin signaling involves 12-lipoxygenase and PKC mediated serine phosphorylation events in melanoma cells. Thromb Haemost 85: 1037-1042, 2001
Dome B, Raso E, Dobos J, et al. Parallel expression of αIIbβ3 and αvβ3 integrins in human melanoma cells upregulates bFGF expression and promotes their angiogenic phenotype. Int J Cancer 116: 27- 35, 2005
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Timar J, Tovari J, Raso E, et al. Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology 69: 185-201, 2005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 218
EP 223
PG 6
ER
PT J
AU Yilmaz, Z
Sahin, IF
Atalay, B
Ozen,
Caner, H
Bavbek, M
Demirhan, B
Altinors, N
AF Yilmaz, Zerrin
Sahin, Iffet Feride
Atalay, Basar
Ozen, Ozlem
Caner, Hakan
Bavbek, Murad
Demirhan, Beyhan
Altinors, Nur
TI Chromosome 1p36 and 22qter Deletions in Paraffin Block Sections of Intracranial Meningiomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE meningioma; 22q; 1p36; fluorescence in situ hybridization; grading
ID meningioma; 22q; 1p36; fluorescence in situ hybridization; grading
AB Meningiomas are the most frequent benign tumors of the intracranial cavity. The classification and underlying pathogenetic mechanisms have been reported to be investigated by both pathological and genetic methods. In this study, we aimed to detect 1p36 and 22qter deletions by fluorescence in situ hybridization (FISH) in archival materials of 50 intracranial meningioma patients. The clinical material consisted of paraffin-embedded tissue sections from 50 patients who were surgically treated and had histopathologic diagnosis of an intracranial meningioma. We observed 1p36 deletion in 23/50 (46%) and 22qter deletion in 33/50 (66%) patients. In addition, we observed 22qter deletion in 26/36 (72.2%) patients with meningothelial meningioma. This finding implies that 22qter deletion might play an important role in the pathogenesis of meningothelial meningioma. On the other hand, no alterations were documented in the frequency of these chromosomal alterations according to the grade of meningiomas, suggesting that malignant progression of these tumors depends on other, more relevant, genetic changes.
C1 [Yilmaz, Zerrin] Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, Kubilay Sokak No: 36 06570-MaltepeAnkara, Turkey.
[Sahin, Iffet Feride] Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, Kubilay Sokak No: 36 06570-MaltepeAnkara, Turkey.
[Atalay, Basar] Baskent University Faculty of Medicine, Department of NeurosurgeryAnkara, Turkey.
[Ozen, Ozlem] Baskent University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Caner, Hakan] Baskent University Faculty of Medicine, Department of NeurosurgeryAnkara, Turkey.
[Bavbek, Murad] Baskent University Faculty of Medicine, Department of NeurosurgeryAnkara, Turkey.
[Demirhan, Beyhan] Baskent University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Altinors, Nur] Baskent University Faculty of Medicine, Department of NeurosurgeryAnkara, Turkey.
RP Sahin, IF (reprint author), Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, Ankara, Turkey.
EM feridesahin@hotmail.com
CR Bello MJ, de Campos JM, Vaquero J et al: High-resolution analysis of chromosome arm 1p alterations in meningioma. Cancer Genet Cytogenet 120: 30-36, 2000
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Freiler A, Zang KD: Monosomy 7p in meningiomas: a rare constituent of tumor progression. Cancer Genet Cytogenet 144:65-68, 2003
Ishino S, Hashimoto N, Fushiki S, et al: Loss of material from chromosome arm 1p during malignant progression of meningioma revealed by fluorescent in situ hybridization. Cancer 83: 360-366, 1998
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Lopez-Gines C, Cerda-Nicolas M, Gil-Benso R, et al: Association of loss of 1p and alterations of chromosome 14 in meningioma progression. Cancer Genet Cytogenet 148: 123-128, 2004
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Sawyer JR, Husain M, Lukacs JL, et al: Telomeric function as a mechanism for the loss of 1p in meningioma. Cancer Genet Cytogenet 145:38-48, 2003
Sayagues JM, Tabernero MD, Diaz P, et al: Incidence of numerical chromosome aberration in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome- specific probes. Cytometry, Clinical Cytometry, 50:153-159, 2002
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Weber RG, Bostrom J, Wolter M, et al: Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: Toward a genetic model of meningioma progression. Proc Natl Acad Sci USA 94: 14719-14724, 1997
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 224
EP 228
PG 5
ER
PT J
AU Behrem, S
Zarkovic, K
Eskinja, N
Jonjic, N
AF Behrem, Senija
Zarkovic, Kamelija
Eskinja, Neven
Jonjic, Nives
TI Distribution Pattern of Tenascin-C in Glioblastoma: Correlation with Angiogenesis and Tumor Cell Proliferation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tenascin; glioblastoma multiforme; angiogenesis; proliferation
ID tenascin; glioblastoma multiforme; angiogenesis; proliferation
AB Tenascin-C (TN-C) is an extracellular matrix protein which participates in different processes like normal fetal development, wound healing, inflammation, keloids and rheumatoid arthritis. Furthermore, the immunostaining for TN-C is seen in the stroma of various malignant tumors as in glioblastoma multiforme (GBM), however, the significance of these findings is still not clear. In this study 62 GBM samples were analyzed immunohistochemically for distribution patterns of TN-C and correlated with angiogenesis and tumor cell proliferation. Tenascin-C in GBM localizes in two compartments, perivascular and intercellular space. Intercellular tenascin-C (TN-C ic) showed focal distribution in 66%, and diffuse one in 34% of cases. Perivascular tenascin-C (TN-C pv) showed strong correlation with microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression. Moreover, it seems that TN-C pv enhanced the effect of VEGF. Intercellular TN-C did not correlate with MVD and VEGF expression, but showed strong correlation with proliferation index. Furthermore, tumors with diffuse TN-C ic expression had higher proliferation indices than tumors with focal TN-C expression. Our results indicate that TN-C plays a role in angiogenesis and tumor cell proliferation, but beside the intensity of expression, the distribution patterns are also important in these processes. This study also suggests that perivascular and intercellular TN-C compartments have probably different sources and different roles in GBM.
C1 [Behrem, Senija] Rijeka University School of Medicine, Department of Pathology, Braaee Branchetta 20, 51 000 Rijeka, Croatia.
[Zarkovic, Kamelija] Clinical Medical Center, Department of NeuropathologyZagreb, Croatia.
[Eskinja, Neven] Clinical Medical Center Rijeka, Department of NeurosurgeryRijeka, Croatia.
[Jonjic, Nives] Rijeka University School of Medicine, Department of Pathology, Braaee Branchetta 20, 51 000 Rijeka, Croatia.
RP Jonjic, N (reprint author), Rijeka University School of Medicine, Department of Pathology, 51 000 Rijeka, Croatia.
EM nives@medri.hr
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Pilch H, Schaffer U, Schlenger K, et al: Expression of tenascin in human cervical cancer: association of tenascin expression with clinicopathological parameters. Gynecol Oncol 73: 415- 421, 1999
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Scheetz FJ, LLoyd PJ: The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Developmental Dynamics 218: 235-259, 2000
Schenk S, Chuquet-Ehrismann R, Battegay EJ: The fibrinogen globe of tenascin-C promotes basic fibroblast growth factorinduced endothelial cell elongation. Mol Biol Cell 10: 2933- 2943, 1999
Tanaka F, Yanagihara OK, Kawano Y, et al: Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 7: 3410-3415, 2001
Tanaka K, Hiraiwa N, Hashimoto H, et al: Tenascin -C regulates angiogenesis in tumor through the regulation of vascular endothelial growth factor expression. Int J Cancer 108: 31-40, 2004
Uhm JH, Gladson LC, Rao JS: The role of integrins in the malignant phenotype of gliomas. Front Biosci 4: 188-199, 1999
Ventimiglia JB, Wikstrand CJ, Ostrowski LE, et al: Tenascin expression in human glioma cell lines and normal tissues. J Neuroimmunol. 36:41-45, 1992
Vitolo D, Paradiso P, Uccini S, et al: Expression of adhesion molecules and extracellular matrix in glioblastomas: relation to angiogenesis and spread. Histopathology 28: 521- 528, 1996
Wehrle-Haller B, Chiquet M: Dual function of tenascin: simultaneous promotion of neural growth and inhibition of glial migration. J Cell Sci 106: 597-610, 1993
Yoshyida T, Yoshimura E, Numata H, et al: Involvement of tenascin-C on proliferation and migration of laryngeal carcinoma cells. Virchows Arch 435: 496-500, 1993
Zagzag D, Friedlander DR, Miller DC, et al: Tenascin expression in astrocytomas correlates with angiogenesis. Cancer Res 55: 907-914, 1995
Zagzag D, Capo V: Angiogenesis in the central nervous system: a role for endothelial growth factor/vascular permeability factor and tenascin-C, common molecular effectors in cerebral neoplastic and non-neoplastic “angiogenic diseases”. Histol Histopathol 17: 301-321, 2002
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 229
EP 235
PG 7
ER
PT J
AU Ghayumi, ASM
Mehrabi, S
Doroudchi, M
Ghaderi, A
AF Ghayumi, Ali Sied Mohammad
Mehrabi, Samrad
Doroudchi, Mehrnossh
Ghaderi, Abbas
TI Diagnostic Value of Tumor Markers for Differentiating Malignant and Benign Pleural Effusions of Iranian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pleural effusion; tumor markers
ID pleural effusion; tumor markers
AB In order to evaluate the diagnostic yield of tumor markers in differentiating malignant and benign pleural effusions, we carried out a prospective study in a group of Iranian people. Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3), neuron-specific enolase (NSE) and cancer antigen 125 (CA 125) were assayed prospectively in patients with pleural effusion (40 malignant and 37 benign). The highest sensitivity was obtained with a combination of CA 15-3 in serum, and CA 15-3 and CEA in pleural fluid (80%), also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid (80%). The highest specificity was obtained with combination of CA 15-3 in serum, and CA 15-3 and NSE in pleural fluid (100%), and also with combination of CA 15-3 in serum, and CA15-3, NSE and CEA in pleural fluid (100%).
C1 [Ghayumi, Ali Sied Mohammad] Shiraz University of Medical Sciences, Department of Internal MedicineShiraz, Iran.
[Mehrabi, Samrad] Shiraz University of Medical Sciences, Department of Internal MedicineShiraz, Iran.
[Doroudchi, Mehrnossh] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Ghayumi, ASM (reprint author), Shiraz University of Medical Sciences, Department of Internal Medicine, Shiraz, Iran.
EM ghayyoumim@sums.ac.ir
CR Chernow B, Sahn SA: Carcinomatous involvement of the pleura: an analysis of 96 patients. Am J Med 63: 695-702, 1977
Marel M, Stastny B, Melinova L, et al: Diagnosis of pleural effusions. Experience with clinical studies, 1986 to 1990. Chest 107: 1598-1603, 1995
Maskell NA, Butland RJ: Pleural Diseases Group, Standards of Care Committee, British Thoracic Society. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 58, Suppl 2): 8-17, 2003
Loddenkemper R: Medical thoracoscopy. In: Textbook of Pleural Diseases., Eds: Light RW, Gray Lee, YC), 2003, pp 498-512
Prakash UB, Reiman HM: Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc 60:158-164, 1985
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Porcel JM, Vives M, Esquerda A, et al: Use of a panel of tumor markers, carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments, in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest 126: 1757-1763, 2004
Richard WL: Tumor markers in undiagnosed pleural effusions. Chest 126: 1721-1722, 2004
Ferrer J, Villarino MA, Encabo G, et al: Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions. Cancer 86: 1488-1495, 1999
Garcia-Pachon E, Padilla-Navas I, Dosda MD, et al: Elevated level of carcinoembryonic antigen in nonmalignant pleural effusions. Chest 111: 643-647, 1997
Alatas F, Alatas O, Metintas M, et al: Diagnostic value of CEA, CA 15-3, CA 19-9, CYFRA 21-1, NSE and TSA assay in pleural effusions. Lung Cancer 31: 9-16, 2001
Ryu JS, Lee HJ, Cho JH, et al: The implication of elevated carcinoembryonic antigen level in pleural fluid of patients with non-malignant pleural effusion. Respirology 8: 487-491, 2003
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Fenton KN, Richardson JD: Diagnosis and management of malignant pleural effusions. Am J Surg 170: 69-74, 1995
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 236
EP 241
PG 6
ER
PT J
AU Ates, EL
Kapran, Y
Erbil, Y
Barbaros, U
Dizdaroglu, F
AF Ates, Esberk Lora
Kapran, Yersu
Erbil, Yesim
Barbaros, Umut
Dizdaroglu, Ferhunde
TI Cystic Lymphangioma of the Right Adrenal Gland
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Adrenal gland; adrenal cyst; lymphangioma
ID Adrenal gland; adrenal cyst; lymphangioma
AB Lymphangiomas are benign malformations of the vessels. They are commonly located in the neck, axillary region and mediastinum. Lymphangioma of the adrenal gland is very rare. These lesions were first discovered as incidental autopsy findings. As the imaging techniques have improved, they now appear as incidental findings at abdominal ultrasonography and computed tomography scan examinations. They are usually asymptomatic. We present a 26-year-old woman admitted to the hospital, complaining of weakness, putting on weight, and lumbago. Her laboratory findings were within normal limits. Radiological examination revealed a 7 cm cystic lesion located in the right adrenal gland. Right adrenalectomy was performed. Histopathological examination and immunohistochemical analysis of the cystic lesion was consistent with a lymphangioma.
C1 [Ates, Esberk Lora] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, Patoloji Anabilim Dali, Capa, 34390 Istanbul, Turkey.
[Kapran, Yersu] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, Patoloji Anabilim Dali, Capa, 34390 Istanbul, Turkey.
[Erbil, Yesim] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Barbaros, Umut] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Dizdaroglu, Ferhunde] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, Patoloji Anabilim Dali, Capa, 34390 Istanbul, Turkey.
RP Ates, EL (reprint author), Istanbul Medical Faculty, Department of Pathology, 34390 Istanbul, Turkey.
EM loraates@hotmail.com
CR Fauquenot-Nollen AM, Plaisier ML, Tjon A, Tham RT: Combined thoracic and abdominal lymphangioma in an adult. JBRBTR 85: 130-131, 2002
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Khoda J, Hertzanu Y, Sebbag G, et al: Adrenal cysts: diagnosis and therapeutic approach. Int Surg 78: 239-242, 1993
Lack EE: Other neoplasm and tumor-like lesions of the adrenal glands. In: Atlas of Tumor Pathology, Tumors of the Adrenal Gland and Extraadrenal Paraganglia., Ed Rosai J), Armed Forces Institute of Pathology, Washington DC, 1997
Longo JM, Jafri SZ, Bis KB: Adrenal lymphangioma: a case report. Clin Imag 24: 104-106, 2000
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Satou T, Uesugi T, Nakai Y, et al: Case of adrenal lymphangioma with atypical lymphocytes in aspirate cytology. Diagn Cytopathol 29: 87-90, 1996
Tagge DU, Baron PL: Giant adrenal cyst: Management and review of the literature. Am Surg 63: 744-746, 1997
Torres C, Ro JY, Batt MA, et al: Vascular adrenal cysts: a clinicopathologic and immunohistochemical study of six cases and review of the literature. Mod Pathol 10: 530-536, 1997
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 242
EP 244
PG 3
ER
PT J
AU Eckhardt, S
AF Eckhardt, Sandor
TI Viral Therapy of Human Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
AB Viral Therapy of Human Cancer JG Sinkovics, JC Horvath (eds), Marcel Dekker New York, 2005, pp 1-829
C1 [Eckhardt, Sandor] National Institute of OncologyBudapest, Hungary.
RP Eckhardt, S (reprint author), National Institute of Oncology, Budapest, Hungary.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2005
VL 11
IS 4
BP 245
EP 245
PG 1
ER
PT J
AU Kopper, L
Timar, J
AF Kopper, Laszlo
Timar, Jozsef
TI Genomics of Renal Cell Cancer - Does It Provide Breakthrough?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE renal cell cancer; genomics; prognostic markers; targeted therapy
ID renal cell cancer; genomics; prognostic markers; targeted therapy
AB It is a strong hope that the more we characterize the pathways in an individual tumor, the better we will be able to evaluate the response to a specific therapy. Different array technologies could be powerful tools to achieve this goal, i.e. selecting patients on the basis of the genomic and/or proteomic profiles who would really benefit from the target-designed therapy. Genomic analysis of RCC accumulated ample of data which now can be exploited in clinical management of a previously almost uncontrollable disease. Beside the previously identified genetic abnormalities (VHL, MET, EGFR), CAIX seems to be a novel molecular marker of RCC. Array studies also outlined a small set of tumor markers, vimentin, galectin-3, CD74 and parvalbumin, which can define the individual histologic subtypes of RCC. We are at the beginning to take advantage of the genomic results. Some new approaches will interfere with the progression of RCC (anti-VEGF, anti-VEGFR or anti-EGFR therapies). Further novel molecular targets are available, such as HIF, HSP90 or the IFN-regulated genes, which can be used to the fine-tuning of RCC therapy.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor ProgressionBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
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Gollob JA: Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma. Clin Genitourin Cancer 4: 167-174, 2005
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Liou LS, Shi T, Duan Z-H, et al: Microarray gene expression profiling and analysis in renal cell carcinoma. BMC Urol 4:1- 11, 2004
Lorincz T, Timar J, Szendroi M: Alterations of microvascular density in bone metastases of adenocarcinoma. Pathol Oncol Res 10: 149-153, 2004
Mekhail TM, Kawanishi-Tabata R, Tubbs R, et al: Renal cell carcinoma, RCC, and telomerase activity: relationship to stage. Urol Oncol 21:424-430, 2003
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Moch H: Genomic alterations in renal tumours: what have we learned in the era of comparative genomic hybridisation? Pathology 36: 51-57, 2004
Motzer RJ, Michaelson D, Redman BG, et al: Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24: 16-24, 2006
Negrier S, Perol D, Menetier-Caux C, et al: Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6 – from the Groupe Francais d’Immunotherapie. J Clin Oncol 22:2371-2378, 2004
Padrik P: Prognostic factors of immunotherapy in metastatic renal cell carcinoma. Med Oncol 20:325-334, 2003
Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA: Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res 9:4641-4652, 2003
Paul R, Necknig U, Busch R, et al: Cadherin-6: a new prognostic marker for renal cell carcinoma. J Urol 171:97-101, 2004
Pavlovich CP, Schmidt LS: Searching for the hereditary causes of renal cell carcinoma. Nat Rev Cancer 4: 381-393, 2004
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Richard S, Lidereau R, Giraud S: The growing family of hereditary renal cell carcinoma. Nephrol Dial Transplant 19: 2954- 2958, 2004
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 5
EP 11
PG 7
ER
PT J
AU Koksal, TI
Ates, M
Danisman, A
Sezer, C
Ciftcioglu, A
Karpuzoglu, G
Sevuk, M
AF Koksal, Turker Ismail
Ates, Mutlu
Danisman, Ahmet
Sezer, Cem
Ciftcioglu, Akif
Karpuzoglu, Gulten
Sevuk, Metin
TI Reduced E-cadherin and α-catenin Expressions Have No Prognostic Role in Bladder Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE E-cadherin; α-catenin; transitional cell carcinoma; urinary bladder
ID E-cadherin; α-catenin; transitional cell carcinoma; urinary bladder
AB In various human cancers, dysfunction of the E-cadherin-catenin complex is associated with a decrease in cellular and tissue differentiation, and with higher invasive and metastatic potentials. The objective of this study was to investigate E-cadherin and α-catenin expression in superficial noninvasive papillary TCC and invasive TCC, and correlate these results with pathological and clinical parameters. We have used immunohistochemistry to localize Ecadherin and α-catenin in 56 formalin-fixed, paraffin-embedded tissue blocks from 41 patients with superficial bladder cancer and 15 with invasive bladder cancer. The 46 male and 10 female patients had a mean age of 67 years, with range of 40 to 82 years. The mean follow-up time was 33.4 (range 5-120) months. Tumor grade 1:2:3 ratios were 5:32:19. In superficial bladder tumor, abnormal expression of E-cadherin and α-catenin was demonstrated in 37 and 71% of the tumors, respectively. In advanced bladder tumor, abnormal expression of E-cadherin and α-catenin was demonstrated in 80 and 100% of the tumors, respectively. Differences in expression of E-cadherin and α-catenin could be discerned between superficial and advanced bladder tumors (p=0.004, p=0.024, respectively). However, the association between E-cadherin and α-catenin expression and tumor grade was not statistically significant (p>0.05). In addition, the expression of E-cadherin and α-catenin did not correlate with tumor number and size (p>0.05). We have demonstrated that abnormal expression of E-cadherin and/or α-catenin occurs in more than 85% of bladder carcinomas and correlates significantly only with advanced stage. Nevertheless, these observations need to be confirmed in larger prospective clinical studies.
C1 [Koksal, Turker Ismail] Akdeniz University, Faculty of Medicine, Department of Urology, Dumlupinar Bulvari, Campus, 07070 Antalya, Turkey.
[Ates, Mutlu] Akdeniz University, Faculty of Medicine, Department of Urology, Dumlupinar Bulvari, Campus, 07070 Antalya, Turkey.
[Danisman, Ahmet] Akdeniz University, Faculty of Medicine, Department of Urology, Dumlupinar Bulvari, Campus, 07070 Antalya, Turkey.
[Sezer, Cem] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Ciftcioglu, Akif] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Karpuzoglu, Gulten] Akdeniz University, Faculty of Medicine, Department of PathologyAntalya, Turkey.
[Sevuk, Metin] Akdeniz University, Faculty of Medicine, Department of Urology, Dumlupinar Bulvari, Campus, 07070 Antalya, Turkey.
RP Koksal, TI (reprint author), Akdeniz University, Faculty of Medicine, Department of Urology, 07070 Antalya, Turkey.
EM tkoksal@akdeniz.edu.tr
CR Abel PD, Henderson D, Bennett MK, et al: Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder. Br J Urol 623: 39-42, 1988.
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International Union Against Cancer, Hermanek P, Sobin LH:, eds, TNM Classification of Malignant Tumors, 5th ed, Springer-Verlag, Germany, 1997.
Koksal IT, Ozcan F, Kilicaslan I, Tefekli A: Expression of E-cadherin in prostate cancer in formalin-fixed, paraffinembedded tissues: correlation with pathological features. Pathology 34: 233-238, 2002.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 13
EP 19
PG 7
ER
PT J
AU Elagoz, S
Egilmez, R
Koyuncu, A
Muslehiddinoglu, A
Arici, S
AF Elagoz, Sahande
Egilmez, Reyhan
Koyuncu, Ayhan
Muslehiddinoglu, Ahmet
Arici, Sema
TI The Intratumoral Microvessel Density and Expression of bFGF and nm23-H1 in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; microvascular density; basic fibroblast growth factor; nm23-H1
ID Colorectal cancer; microvascular density; basic fibroblast growth factor; nm23-H1
AB It has previously been reported that intratumoral microvessel density (IMD), and the expression of bFGF and nm23-H1 are useful prognostic markers in colorectal cancer (CRC). In this study, a total of 100 CRCs were evaluated histopathologically, and IMD, bFGF and nm23-H1 expression were assessed by immunohistochemistry. IMD of patients increased with grade and stage, and this increase was statistically significant (p<0.05). A significantly higher incidence of high bFGF expression scores was also associated with increasing grade and stage (p<0.05). However, there was no significant difference between the grades in nm23-H1 expression (p=0.234). nm23-H1 expression occurred with lower incidence in stages C1, C2 and D than in stages B1 and B2 (p<0.05). Thus, a negative correlation was found between nm23-H1 expression and stage or lymph node metastasis (LNM) (p<0.05). IMD and bFGF expression were positively correlated with grade, stage, LNM, and lymphovascular invasion. Although positive correlation was found between IMD and bFGF, nm23-H1 expression negatively correlated with both of them. As a result, in clinical practice, increased IMD and bFGF expression and decreased nm23-H1 expression may provide valuable information in characterizing the malignant phenotype.
C1 [Elagoz, Sahande] Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey.
[Egilmez, Reyhan] Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey.
[Koyuncu, Ayhan] Cumhuriyet University School of Medicine, Department of General SurgerySema, Turkey.
[Muslehiddinoglu, Ahmet] Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey.
[Arici, Sema] Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey.
RP Elagoz, S (reprint author), Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey.
EM selagoz@cumhuriyet.edu.tr
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Sarris M, Lee CS: Nm23-H1 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. Eur J Surg Oncol 27: 170-174, 2001
Soliani P, Ziegler S, Romani A et al: Prognostic significance of nm23-H1 gene product expression in patients with colorectal carcinoma treated with radical intent. Oncol Rep 11: 1193- 1200, 2004
Dursun A, Akyurek N, Gunel N, et al: Prognostic implication of nm23-H1 expression in colorectal carcinomas. Pathology 34: 427-432, 2002
Dusonchet L, Corsale S, Migliavacca M et al: Nm23-H1 expression does not predict clinical survival in colorectal cancer patients. Oncol Rep 10: 1257-1263, 2003
Royds JA, Cross SS, Silcocs PB, et al: Nm23-H1 “anti-metastatic” gene product expression in colorectal carcinoma. J Pathol 172: 261-266, 1994
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 21
EP 27
PG 7
ER
PT J
AU Pezeshki, A
Sari-Aslani, F
Ghaderi, A
Doroudchi, M
AF Pezeshki, Abdulmohammad
Sari-Aslani, Fatemeh
Ghaderi, Abbas
Doroudchi, Mehrnoosh
TI p53 Codon 72 Polymorphism in Basal Cell Carcinoma of the Skin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE basal cell carcinoma; p53; polymorphism; sun exposure
ID basal cell carcinoma; p53; polymorphism; sun exposure
AB Basal cell carcinoma (BCC) is the most prevalent cancer in Iran. A common polymorphism at codon 72 of exon 4 of p53 tumor suppressor gene has been reported to be associated with increased inheritable susceptibility to several cancers. In the present study the frequency of p53 codon 72 polymorphism in 91 patients with BCC of skin, compared to 465 healthy normal individuals, was investigated. In total, there was no significant difference in the p53 genotypes between patients and controls. However, there was an apparent increase in the Arg/Arg genotype among those BCC patients who had a history of occupational sun exposure, compared to non-exposed patients (46.3% vs. 23.1%, P=0.11). A trend of increase in the frequency of Arg allele among sun-exposed patients was also observed (69.4% vs. 53.8%, P=0.07). Comparison of the genotype frequencies between sunexposed patients and normal controls confirmed the accumulation of Arg/Arg genotype in these patients (46.3% vs. 34.8%, P = 0.07). In addition, the frequency of Arg allele was significantly higher in sunexposed patients compared to controls (69.4% vs. 58.2%, P=0.03). Our results suggest that Arg allele at codon 72 of p53 gene might affect the risk of ultraviolet-induced basal cell carcinoma.
C1 [Pezeshki, Abdulmohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Sari-Aslani, Fatemeh] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Doroudchi, Mehrnoosh] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Doroudchi, M (reprint author), Shiraz University of Medical Sciences, Institute for Cancer Research, Shiraz, Iran.
EM mdoroud@sums.ac.ir
CR de Gruijl FR, van Kranen HJ, Mullenders LH: UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. J Photochem Photobiol 63: 19-27, 2001
Kim MY, Park HJ, Baek SC, et al: Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias. J Dermatol Sci 29: 1-9, 2002
McGregor JM, Harwood CA, Brooks L, et al: Relationship between p53 codon 72 polymorphism and susceptibility to sunburn and skin cancer. J Invest Dermatol 119: 84-90, 2002
Murata M, Tagawa M, Kimura M, et al: Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history. Carcinogenesis 17: 261-264, 1996
Dumont P, Leu JI, Della Pietra AC, et al: The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33: 357-365, 2003
Buchman VL, Chumakov PM, Ninkina NN, et al: A variation in the structure of the protein-coding region of the human p53 gene. Gene 70: 245-252, 1988
Marin MC, Jost CA, Brooks LA, et al: A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet 25: 47-54, 2000
Tada M, Furuuchi K, Kaneda M, et al: Inactivate the remaining p53 allele or the alternate p73? Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants. Carcinogenesis 22: 515-517, 2001
Marshall SE, Bordea C, Wojnarowska F, et al: p53 codon 72 polymorphism and susceptibility to skin cancer after renal transplantation. Transplantation 69: 994-996, 2000
Makni H, Franco EL, Kaiano J, et al: p53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: effect of inter-laboratory variation. Int J Cancer 87: 528-533, 2000
Nagpal JK, Sahni S, Das BR: p53 codon 72 polymorphism and susceptibility to development of human papilloma virus-associated cervical cancer in Indian women. Eur J Clin Invest 32: 943-948, 2002
Qie M, Zhang Y, Wu J: Study on the relationship between cervical cancer and p53 codon 72 polymorphism. Hua Xi Yi Ke Da Xue Xue Bao 33: 274-275, 2002
Li T, Lu ZM, Guo M, et al: p53 codon 72 polymorphism, C/G, and the risk of human papillomavirus-associated carcinomas in China. Cancer 95: 2571-2576, 2002
Pegoraro RJ, Moodley M, Rom L, et al: p53 codon 72 polymorphism and BRCA 1 and 2 mutations in ovarian epithelial malignancies in black South Africans. Int J Gynecol Cancer 13: 444-449, 2003
Suzuki K, Matsui H, Ohtake N, et al: A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese. J Biomed Sci 10: 430-435, 2003
Cenci M, French D, Pisani T, et al: p53 polymorphism at codon 72 is not a risk factor for cervical carcinogenesis in central Italy. Anticancer Res 23: 1385-1387, 2003
Abba MC, Villaverde LM, Gomez MA, et al: The p53 codon 72 genotypes in HPV infection and cervical disease. Eur J Obstet Gynecol Reprod Biol 109: 63-66, 2003
Anzola M, Cuevas N, Lopez-Martinez M, et al: Frequent loss of p53 codon 72 Pro variant in hepatitis C virus-positive carriers with hepatocellular carcinoma. Cancer Lett 193: 199-205, 2003
Buyru N, Budak M, Yazici H, Dalay N: p53 gene mutations are rare in human papillomavirus-associated colon cancer. Oncol Rep 10: 2089-2092, 2003
Humbey O, Cairey-Remonnay S, Guerrini JS, et al: Detection of the human papillomavirus and analysis of the TP53 polymorphism of exon 4 at codon 72 in penile squamous cell carcinomas. Eur J Cancer 39: 684-690, 2003
Soulitzis N, Sourvinos G, Dokianakis DN, Spandidos DA: p53 codon 72 polymorphism and its association with bladder cancer. Cancer Lett 179: 175-183, 2002
International Agency for Research on Cancer: Solar and Ultraviolet Radiation, vol. 55, International Agency for Research on Cancer, Lyon, 1992
Weihrauch M, Bader M, Lehnert G, et al: Carcinogen-specific mutation pattern in the p53 tumor suppressor gene in UV radiation- induced basal cell carcinoma. Int Arch Occup Environ Health 75: 272-276, 2002
Ananthaswamy HN, Loughlin SM, Cox P, et al: Sunlight and skin cancer: inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens. Nat Med 3: 510-514, 1997
Feynman RP, Leighton SM, In: The Feynman lectures on Physics, Vol. III. Addison-Weseley, Reading, MA, 1967, pp.15-7-15-12
Ziegler AD, Leffel DJ, Kunala S, et al: Mutation hotspots due to sunlight in the p53 gene of non-melanoma skin cancers. Proc Natl Acad Sci USA 90: 4216-4220, 1993
Farahmandbeigi M, Kadivar MR: The incidence rate of registered cancers in Fars province. Disease Control Unit, Shiraz University Press, Iran, 2000
Baron JA, Greenberg ER: Prevention of non-melanoma skin cancer. Arch Dermatol 136: 245-246, 2000
Argorastos T, Lambropoulos AF, Constantinidis TC, et al: p53 codon 72 polymorphism and risk of intra-epithelial and invasive cervical neoplasia in Greek women. Eur J Cancer Prev 9: 113-118, 2000
Armstrong BK, Kricker A: The epidemiology of UV induced skin cancer. J Photochem Photobiol B 63: 8-18, 2001
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 29
EP 33
PG 5
ER
PT J
AU Pal, J
Nyarady, Z
Marczinovits, I
Par, A
Ali, SY
Berencsi, Gy
Kvell, K
Nemeth, P
AF Pal, Jozsef
Nyarady, Zoltan
Marczinovits, Ilona
Par, Alajos
Ali, Saleh Younes
Berencsi, Gyorgy
Kvell, Krisztian
Nemeth, Peter
TI Comprehensive Regression Analysis of Hepatitis B Virus X Antigen Level and Anti-HBx Antibody Titer in the Sera of Patients with HBV Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatitis B virus; HBxAg; immunoserology; epitope mapping; antibody response
ID Hepatitis B virus; HBxAg; immunoserology; epitope mapping; antibody response
AB Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various - biologically active - epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections.
C1 [Pal, Jozsef] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Nyarady, Zoltan] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Marczinovits, Ilona] University of Szeged, Department of AnatomySzeged, Hungary.
[Par, Alajos] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Ali, Saleh Younes] University of Garyounis, Faculty of MedicineBenghazi, Libyan Arab Jamabiriya.
[Berencsi, Gyorgy] ANTSZ Regional Institute of State Public Health Service, Regional Laboratory of VirologyPecs, Hungary.
[Kvell, Krisztian] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti u. 12., H-7643 Pecs, Hungary.
RP Nemeth, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM peter.nemeth@aok.pte.hu
CR Altschul SF, Madden TL, Schaffer AA, et al: “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs”. Nucleic Acids Res 25: 3389-3402,1997
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Caselmann WH: Trans-activation of cellular genes by hepatitis B virus proteins: A possible mechanism of hepatocarcinogenesis. Adv Virus Res 47: 253-302, 1996
Feitelson MA, Clayton MM, Blumberg BS: X antigen/antibody markers in hepadnavirus infections. Presence and significance of the hepadnavirus X gene product(s, in serum. Gastroenterology 98: 1071-1078, 1990
Hann HW, Lee J, Bussard A, et al: Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma. Cancer Res 64: 7329-7335, 2004
Hwang GY, Lin CY, Huang LM, et al: Detection of the hepatitis B virus X protein, HBx, antigen and anti-HBx antibodies in cases of human hepatocellular carcinoma. J Clin Microbiol 41: 5598-5603, 2003
Jung MC, Stemler M, Weimer T, et al: Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus. Hepatology 13: 637-643, 1991
Kumar V, Jayasuryan N, Kumar R: A truncated mutant, residues 58- 140, of the hepatitis B virus X protein retains transactivation function. Proc Natl Acad Sci USA 93:5647-5652, 1996
Malik AH, Lee WM: Chronic hepatitis B virus infection: treatment strategies for the next Millennium. Lee Ann Intern Med 132: 723- 731, 2000
Marczinovits I, Somogyi C, Patthy A, et al: An alternative purification protocol for producing hepatitis B virus X antigen on a preparative scale in Escherichia coli. J Biotechnol 56: 81-88, 1997
Misra KP, Mukherji A, Kumar V: The conserved amino-terminal region, amino acids 1-20, of the hepatitis B virus X protein shows a transrepression function. Virus Res 105: 157-165, 2004
Murakami S, Cheong JH, Kaneko S: Human hepatitis virus X gene encodes a regulatory domain that represses transactivation of X protein. J Biol Chem 269: 15118-15123, 1994
Murakami S: Hepatitis B virus X protein. Structure, function and biology. Intervirology 42: 81-99, 2001
Murakami S: Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol 36: 651-660, 1999
Ordog K, Szendroi A, Szarka K, et al: Perinatal and intrafamily transmission of hepatitis B virus in three generations of a low-prevalence population. J Med Virol 70: 194-204, 2003
Pal J, Czompoly T, Nyarady Z, et al: Determination of the fine epitope specificity of an anti-hepatitis B virus X protein monoclonal antibody using microanalytical and molecular biological methods. Mol Immunol 40: 241-246, 2003
Pal J, Palinkas L, Nyarady Z, et al:Sandwich type ELISA and a fluorescent cytometric microbead assay for quantitative determination of Hepatitis B virus X antigen level in human sera. J Immunol Methods, 2005, accepted for publication)
Pal J, Somogyi C, Szmolenszky AA, et al: Immunohistochemical assessment and prognostic value of hepatitis B virus X protein in chronic hepatitis and primary hepatocellular carcinomas using anti- HBxAg monoclonal antibody. Pathol Oncol Res 7: 178-184, 2001
Song CZ, Wang QW, Song CC, Bai ZL: Viral replication modulated by synthetic peptide derived from hepatitis B virus X protein. World J Gastroenterol 10: 389-392, 2004
Stemler M, Weimer T, Tu ZX, et al: Mapping of B-cell epitopes of the human hepatitis B virus X protein. J Virol 64: 2802-2809, 1990
Tiollais P, Pourcel C, Dejan A: The hepatitis B virus. Nature 317: 489-495, 1985
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 34
EP 40
PG 7
ER
PT J
AU Saqui-Salces, M
Martinez-Benitez, B
Gamboa-Dominguez, A
AF Saqui-Salces, Milena
Martinez-Benitez, Braulio
Gamboa-Dominguez, Armando
TI EBV+ Lymphoepithelial Carcinoma of the Parotid Gland in Mexican Mestizo Patients with Chronic Autoimmune Diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE lymphoepithelial carcinoma; Epstein-Barr virus; autoimmune disease; salivary glands
ID lymphoepithelial carcinoma; Epstein-Barr virus; autoimmune disease; salivary glands
AB Lymphoepithelial carcinomas of the salivary gland are rare tumors constantly associated with Epstein-Barr virus (EBV) and mainly identified in Asiatic and Greenlander population. Four cases have been described in Caucasians, only two with EBV infection. We describe two cases of parotid gland lymphoepithelial carcinomas in Mexican mestizo women in which chronic latent EBV infection was documented by immunohistochemistry and in situ hybridization. One patient had primary Sjogren’s syndrome and the other systemic lupus erythematosus of six and three years of evolution, respectively. Epithelial neoplastic cells showed latency pattern II (LMP1+, EBNA-2-, EBER+) with a dense inflammatory infiltrate composed mainly by CD8+ T lymphocytes. Follow-up excluded nasopharyngeal involvement in both patients. This report expands the ethnic groups in which salivary lymphoepithelial carcinomas associated with chronic latent EBV infection have been described, and illustrates for the first time its association with autoimmune diseases in two women living in a region non-endemic for this unusual neoplasm.
C1 [Saqui-Salces, Milena] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No 15, 14000 Tlalpan, Mexico.
[Martinez-Benitez, Braulio] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No 15, 14000 Tlalpan, Mexico.
[Gamboa-Dominguez, Armando] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, Vasco de Quiroga No 15, 14000 Tlalpan, Mexico.
RP Gamboa-Dominguez, A (reprint author), Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Pathology, 14000 Tlalpan, Mexico.
EM agamboad@quetzal.innsz.mx
CR Abu-Shakra M, Ehrenfeld M, Shoenfeld Y: Systemic lupus erythematosus and cancer: associated or not? Lupus 11:137-144, 2002
Albeck H, Nielsen NH, Hansen HE, et al: Epidemiology of nasopharyngeal and salivary carcinoma in Greenland. Artic Med Res 51:189-195, 1992
Bialas M, Sinczak A, Choinska-Stefanska A, Zygulska A: EBVpositive lymphoepithelial carcinoma of salivary gland in a woman of a non-endemic area—a case report. Pol J Pathol 53:235-238, 2002
Bjornadal L, Lofstrom B, Yin L, et al: Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol 31:66-71, 2002
Chan JKC, Yip TTC, Tsang WYW: Specific association of Epstein-Barr virus with lymphoepithelial carcinoma among tumors and tumor like lesions of the salivary gland. Arch Pathol Lab Med 118: 994-997, 1994
Hamilton-Dutoit SJ, Therkildsen MH, Nielsen NH: Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic hybridization. Hum Pathol 22: 811-815, 1991
Jen KY,Cheng J, Li J, et al: Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas. Int J Cancer 105: 654-660, 2003
Kang I, Quan T, Nolasco H: Defective control of latent Epstein- Barr virus infection in systemic lupus erythematosus. J Immunol 172: 1287-1294, 2004
Kotsianti A, Costopoulos J, Morgello S, Papadimitriou C: Undifferentiated carcinoma of the parotid gland in a white patient: detection of Epstein-Barr virus by in situ hybridization. Hum Pathol 27: 87-90, 1996
Kuo T, Hsue C: Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein-Barr virus. Histopathology 31: 75-82, 1997
Leung SY, Chung LP, Yuen ST: Lymphoepithelial carcinoma of the salivary gland: in situ detection of EBV. J Clin Pathol 48:1022-1027, 1995
Lin CL, Lo WF, Lee TH: Immunization with EBV peptidepulsed dendritic cells induces functional CD8+T-Cell immunity and may lead to tumor regression in EBV-positive NPC. Cancer Res 62:6952-6958, 2002
Niedobitek G, Meru N, Delecluse HJ: Epstein-Barr virus infection and human malignancies. Int J Exp Pathol 82:149-170, 2001
Quintanilla-Martinez L, Gamboa-Dominguez A, Gamez-Ledesma I, et al: Prevalencia alta del virus de Epstein-Barr en una poblacion mexicana con enfermedad de Hodgkin. Rev Invest Clin 46: 355-362, 1994
Saku T, Cheng J, Jen KY, et al: Epstein-Barr virus infected lymphoepithelial carcinomas of the salivary gland in the Russia- Asia area: a clinicopathologic study of 160 cases. Arkh Patol 65: 35-39, 2003
Tsai C-C, Chen C-L, Hsu H-C: Expression of Epstein Barr virus in carcinomas of salivary glands: a strong association with lymphoepithelioma-like carcinoma. Hum Pathol 27:258- 262, 1996
Villa AR, Kraus A, Jimenez-Corona A: Malignant neoplasms in autoimmune rheumatic diseases: examination of the risk of developing a malignancy among five different rheumatic diseases in one institution. J Clin Rheumatol 6:176-183, 2000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 41
EP 45
PG 5
ER
PT J
AU Sobel, G
Halasz, J
Bogdanyi, K
Szabo, I
Borka, K
Molnar, P
Schaff, Zs
Paulin, F
Banhidy, F
AF Sobel, Gabor
Halasz, Judit
Bogdanyi, Katalin
Szabo, Istvan
Borka, Katalin
Molnar, Peter
Schaff, Zsuzsa
Paulin, Ferenc
Banhidy, Ferenc
TI Prenatal Diagnosis of a Giant Congenital Primary Cerebral Hemangiopericytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE congenital brain tumors; infantile hemangiopericytoma
ID congenital brain tumors; infantile hemangiopericytoma
AB Congenital primary intracranial hemangiopericytomas are exceptionally rare tumors. We present a case of a fetus, with the prenatal sonogram at 33 weeks of gestation revealing a large cerebral tumor. Because of the enlarged head, a cesarean section was performed. The tumor was confirmed by postnatal ultrasound, magnetic resonance imaging (MRI) and biopsy. Elevated intracranial pressure and hemorrhage led to death on the 11th day. Autopsy revealed a 10x9 cm large inhomogeneous tumor located centrally, mainly in the posterior fossa. Histology showed a hypercellular and hypervascular tumor with extended necrosis and high mitotic rate. The tumor cells were positive for vimentin and CD34 antigens and negative for several neurological markers, desmin and CD31. The diagnosis of a congenital primary cerebral hemangiopericytoma was confirmed.
C1 [Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Halasz, Judit] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Bogdanyi, Katalin] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Szabo, Istvan] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Borka, Katalin] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Molnar, Peter] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Paulin, Ferenc] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Banhidy, Ferenc] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Janisch W, Haas JF, Schreiber D, et al: Primary central nervous system tumors in stillborns and infants. Epidemiological considerations. J Neurooncol 2: 113-116, 1984
Jellinger K, Sunder-Plassmann M: Connatal intracranial tumours. Neuropaediatrie 4: 46-63, 1973
Lee D-Y, Kim Y-M, Yoo S-J, et al: Congenital glioblastoma diagnosed by fetal sonography. Child’s Nerv Syst 15: 197-201, 1999
Nakayama K, Nakamura Y: Localization of congenital glioblastomas in the Japanese: a case report and review of the literature. Child’s Nerv Syst 18: 149-152, 2002
Winters JL, Wilson D, Davis DG: Congenital glioblastoma multiforme: a report of three cases and a review of the literature. J Neurol Sci 188: 13-19, 2001
Leins AM, Kainer R, Weis S, et al: Sonography and neuropathology of a congenital brain tumor: report of a rare incident. Ultrasound Obstet Gynecol 17: 245-247, 2001
Aouad N, Vital C, Rivel J, et al: Giant supratentorial meningeal haemangiopericytoma in a newborn. Acta Neurochirurg 112: 154-156, 1991
Herzog CE, Leeds NE, Bruner JM, et al: Intracranial hemangiopericytomas in children. Ped Neurosurg 22: 274-279, 1995
Hodaie M, Becker L, Teshima I, et al: Total resection of an intracerebral hemangioendothelioma in an infant. Case report and review of the literature. Pediatr Neurosurg 34: 104-112, 2001
Kirk IR, Dominguez R, Castillo M: Congenital primary cerebral angiosarcoma: CT, US, and MR findings. Pediatr Radiol 22: 134-135, 1992
Mena H, Ribas JL, Enzinger FM, et al: Primary angiosarcoma of the central nervous system. J Neurosurg 75: 73-76, 1991
Suzuki Y, Yoshida YK, Shirane R, et al: Congenital primary cerebral angiosarcoma. J Neurosurg 92: 466-468, 2000
Alen JF, Lobato RD, Gomez PA, et al: Intracranial hemangiopericytoma: study of 12 cases. Acta Neurochir, Wien, 143: 575-586, 2001
Calonje E, Fletcher CDM: Tumors of blood vessels and lymphatics. In: Diagnostic Histopathology of Tumors., Eds: Fletcher CDM), Vol. 1, Second ed., Churchill Livingstone, London, 2000, pp. 45-86
Ordonez NG, Mackay B, el-Naggar AK, et al: Congenital hemangiopericytoma. An ultrastructural, immunocytochemical, and flow cytometric study. Arch Pathol Lab Med 117: 934-937, 1993
Johnson MD, Mitchell AR, Troup EC, et al: Congenital cystic hemangioblastomas of the cerebral hemisphere in a neonate without alteration in the VHL gene. Pediatr Neurosurg 40: 124-127, 2004
Weiss SW, Goldblum JR: Perivascular tumors. In: Enzinger and Weiss’s Soft Tissue Tumors., Eds: Weiss SW and Goldblum JR), Fourth ed., Mosby, St. Louis, 2001, pp. 985-1037
Beckner ME, Sasatomi E, Swalsky PA, et al: Loss of heterozygosity reveals non-VHL allelic loss in hemangioblastomas at 22q13. Hum Pathol 35: 1105-1111, 2004
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 46
EP 49
PG 4
ER
PT J
AU Culhaci, N
Ozkara, E
Yuksel, H
Ozsunar, Y
Unal, E
AF Culhaci, Nil
Ozkara, Esra
Yuksel, Hasan
Ozsunar, Yelda
Unal, Emel
TI Spontaneously Ruptured Uterine Angioleiomyoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE angioleiomyoma; uterus; genital tract
ID angioleiomyoma; uterus; genital tract
AB Angioleiomyoma is an uncommon type of leiomyoma of the uterus that originates from smooth muscle cells and contains thick-walled vessels. A 45-year-old woman with the complaint of lower abdominal pain was admitted to the hospital. In the operation a ruptured, bleeding uterine tumor was seen. She underwent total hysterectomy and bilateral salpingo-oophorectomy. On pathologic examination of the specimen, the tumor was diagnosed as angioleiomyoma. Here, an unusual clinical presentation of uterine angioleiomyoma was reported.
C1 [Culhaci, Nil] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Ozkara, Esra] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
[Yuksel, Hasan] Adnan Menderes University, Faculty of Medicine, Department of Obstetrics and GynecologyAydin, Turkey.
[Ozsunar, Yelda] Adnan Menderes University, Faculty of Medicine, Department of RadiologyAydin, Turkey.
[Unal, Emel] Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
RP Culhaci, N (reprint author), Adnan Menderes University, Medical Faculty, Pathology Department, 09100 Aydin, Turkey.
EM nculhaci@adu.edu.tr
CR Weiss SW, Goldblum JR: Benign tumors of smooth muscle. In: Enzinger and Weiss’s soft tissue tumors. 4th ed., Mosby, St. Louis, 2001, pp 699-700
Zaloudek C, Hendrickson MR: Mesenchymal tumors of the uterus. In: Blaustein’s Pathology of the Female Genital Tract., Ed.: Kurman R), 5th ed, Springer-Verlag, New York, 2002, pp 574
Hennig Y, Caselitz J, Stern C, et al: Karyotype evolution in a case of uterine angioleiomyoma. Cancer Genet Cytogenet 108: 79-80, 1999
Wang CP, Chang YL, Sheen TS: Vascular leiomyoma of the head and neck. Laryngoscope 114: 661-665, 2004
Ide F, Mishima K, Saito I: Angiomyoma in the submandibular gland: a rare location for a ubiquitous tumour. J Laryngol Otol 117: 1001-1002, 2003
Hsieh CH, Lui CC, Huang SC, et al: Multiple uterine angioleiomyomas in a woman presenting with severe menorrhagia. Gynecol Oncol 90: 348-352, 2003
Stewart EA, Nowak RA: Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update 2: 295-306, 1996
Agorastos T, Dinas K, Patsiaoura K: Cystic degenerated angioleiomyoma mimicking ovarian pathology. Acta Obstet Gynecol Scand 80: 863-865, 2001
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 50
EP 51
PG 2
ER
PT J
AU Szilasi, M
Dolinay, T
Nemes, Z
Strausz, J
AF Szilasi, Maria
Dolinay, Tamas
Nemes, Zoltan
Strausz, Janos
TI Pathology of Chronic Obstructive Pulmonary Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE chronic bronchitis; obstructive bronchiolitis; emphysema; inflammation
ID chronic bronchitis; obstructive bronchiolitis; emphysema; inflammation
AB Chronic obstructive pulmonary disease is one of the leading causes of death and morbidity worldwide. Despite intensive investigation, its pathology and pathophysiology are not well understood. The hallmarks of the disease are irreversible airflow limitation and chronic inflammation. Small airway obstruction due to progressive inflammation and fibrosis, and the loss of elastic recoil mediated by elastolysis and apoptosis equally contribute to pathologic changes. However, it is debated to what extent the obstruction of large airways leads to altered lung function. Three morphologic entities are described in the literature under one disease; chronic bronchitis, obstructive bronchiolitis and emphysema may appear in the same patient at the same time. The authors review pathologic changes observed in chronic obstructive pulmonary disease, including acute exacerbations and secondary pulmonary hypertension as severe but common complications of the disease. Furthermore, we detail recent scientific evidences for major cellular and molecular inflammatory pathway activation. These mechanisms result in accelerated apoptosis, remodeling and increased proinflammatory cytokine release. Targeting intracellular pathological changes may lead to the discovery of a new generation of drugs that could reduce chronic obstruction before airway irreversibility is established.
C1 [Szilasi, Maria] University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, Moricz Zs. krt. 22., H-4004 Debrecen, Hungary.
[Dolinay, Tamas] University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, Moricz Zs. krt. 22., H-4004 Debrecen, Hungary.
[Nemes, Zoltan] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Strausz, Janos] National Koranyi Institute of PulmonologyBudapest, Hungary.
RP Szilasi, M (reprint author), University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, H-4004 Debrecen, Hungary.
EM mszilasi@jaguar.unideb.hu
CR Aoshiba K, Yokohori N, Nagai A: Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol 28: 555-562, 2003
Boszormenyi Nagy G: Chronic obstructive pulmonary disease. In: Epidemiology and Functional Data in Pulmonology Institutions in year 2004 [book in Hungarian], Eds: Jonas J, Fodor K, Turgyei M and Nyari L), Orszagos Koranyi TBC es Pulmonologiai Intezet, 2005, pp. 50-56
Chodosh S: Treatment of acute exacerbations of chronic bronchitis: state of the art. Am J Med 91: 87S, 1991
Daheshia M: Therapeutic inhibition of matrix metalloproteinases for the treatment of chronic obstructive pulmonary disease, COPD). Curr Med Res Opin 21: 587-593, 2005
de Dodoy I, Donahoe M, Calhoun WJ, et al: Elevated TNFalpha production by peripheral blood monocytes of weightloosing COPD patients. Am J Respir Crit Care Med 153: 633- 637, 1996
Deshmukh HS, Case LM, Wesselkamper SC: Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation. Am J Respir Crit Care Med 171: 305-314, 2005
Di Stefano A, Capelli A, Lusuardi M, et al: Severity of airflow limitation is associated with severity of airway inflammation in smokers. Am J Respir Crit Care Med 158: 1277-1285, 1998
Drost EM, Skwarski J, Sauleda J, et al: Oxidative stress and airway inflammation in severe extracerbations of COPD. Thorax 60: 293-300, 2005
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Fletcher C, Peto R, Tinker C, et al: The natural history of chronic bronchitis and emphysema: an eight-year study of early chronic obstructive lung disease in working men in London. Oxford University Press, Oxford, England: 93, 1976
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Haraguchi M, Shimura S, Shirato K: Morphometric analysis of bronchial cartilage in chronic obstructive pulmonary disease and bronchial asthma. Am J Respir Crit Care Med 159: 1005- 1013, 1999
Hogg JC, Chu F, Utokaparch S, et al: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350: 2645-2653, 2004
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Kasahara Y, Tunder RM, Taraseviciene-Stewart L, et al: Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106: 1311-1319, 2000
Keatings VM, Collins PD, Scott DM, et al: Differences in interleukin- 8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 153: 530-534, 1996
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Lams BE, Sousa AR, Rees PJ, Lee TH: Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease. Eur Respir J 15: 512- 516, 2000
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McCrory DC, Brown C, Gelfand SE, et al: Management of acute exacerbation of COPD: a summary and appraisal of published evidence. Chest 119: 1190-1209, 2001
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Miotto D, Hollenberg MD, Bunnett NW, et al: Expression of protease activated receptor-2, PAR-2, in central airways of smokers and non-smokers. Thorax 57: 146-151, 2002
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Saetta M, Baraldo S, Corbino L, et al: CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 160: 711-717, 1999
Saetta M, Di Stefano A, Maestrelli P, et al: Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis. Am Rev Respir Dis 147: 301-306, 1993
Saetta M, Di Stefano A, Maestrelli P, et al: Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med 150: 1646-1652, 1994
Saetta M, Di Stefano A, Turato G, et al: CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157: 822-826, 1998
Saetta M, Turato G, Baraldo S, et al: Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med 161: 1016-1021, 2000
Saetta M, Turato G, Maestrelli P, et al: Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 163: 1304-1309, 2001
Saint S, Bent S, Vittinghoff E, et al: Antibiotics in chronic obstructive pulmonary disease exacerbation: A meta-analysis. JAMA 273: 957-960, 1995
Santos S, Peinado VI, Ramirez J, et al: Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 167: 1250-1256, 2003
Segura-Valdez L, Pardo A, Gaxiola M: Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 117: 684-694, 2000
Seti S, Evans N, Grant BJ, et al: New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 347: 465-473, 2002
Snider GL: Chronic obstructive pulmonary disease: a continuing challenge. Am Rev Respir Dis 133: 942-944, 1986
Takeyama K, Dabbagh K, Lee HM, et al: Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci U S A 96: 3081-3086, 1999
ten Hacken NH, Postma DS, Timens W: Are asthma and chronic obstructive pulmonary disease different diseases?--Con. Monaldi Arch Chest Dis 54: 551-558, 1999
Tuder RM, Zhen L, Cho CY, et al: Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. Am J Respir Cell Mol Biol 29: 88-97, 2003
Vestbo J, Lange P: Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 66: 329-332, 2002
Vestbo J, Prescott E, Lange P: Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Am J Respir Crit Care Med 153: 1530-1535, 1996
Vlahovic G, Russell ML, Mercer RR, et al: Cellular and connective tissue changes in alveolar septal wall in emphysema. Am J Respir Crit Care Med 160: 2086-2092, 1999
Vliagoftis H, Schwingshackl A, Milne CD, et al: Proteinaseactivated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells. J Allergy Clin Immunol 106: 537-545, 2000
Zheng T, Kang MJ, Crothers K, et al: Role of cathepsin Sdependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema. J Immunol 174: 8106-8115, 2005
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 52
EP 60
PG 9
ER
PT J
AU Kopper, L
Timar, J
AF Kopper, Laszlo
Timar, Jozsef
TI Professor Karoly LAPIS, a Hungarian pathologist, is 80
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor ProgressionBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2006
VL 12
IS 1
BP 61
EP 61
PG 1
ER
PT J
AU Sulkowska, M
Golaszewska, J
Wincewicz, A
Koda, M
Baltaziak, M
Sulkowski, S
AF Sulkowska, Mariola
Golaszewska, Jolanta
Wincewicz, Andrzej
Koda, Mariusz
Baltaziak, Marek
Sulkowski, Stanislaw
TI Leptin - From Regulation of fat Metabolism to Stimulation of Breast Cancer Growth
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE leptin; leptin receptor; signal transducer and activator of transcription 3; estrogen receptor alpha; antiestrogen resistance
ID leptin; leptin receptor; signal transducer and activator of transcription 3; estrogen receptor alpha; antiestrogen resistance
AB Leptin restricts intake of calories as a satiety hormone. It probably stimulates neoplastic proliferation in breast cancer, too. Growth of malignant cells could be regulated by various leptin-induced second messengers like STAT3 (signal transducers and activators of transcription 3), AP-1 (transcription activator protein 1), MAPK (mitogen-activated protein kinase) and ERKs (extracellular signal-regulated kinases). They seem to be involved in aromatase expression, generation of estrogens and activation of estrogen receptor ? (ER?) in malignant breast epithelium. Leptin may maintain resistance to antiestrogen therapy. Namely, it increased activation of estrogen receptors, therefore, it was suspected to reduce or even overcome the inhibitory effect of tamoxifen on breast cell proliferation. Although several valuable reviews have been focused on the role of leptin in breast cancer, the status of knowledge in this field changes quickly and our insight should be continuously revised. In this summary, we provide refreshed interpretation of intensively reported scientific queries of the topic.
C1 [Sulkowska, Mariola] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Golaszewska, Jolanta] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Wincewicz, Andrzej] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Koda, Mariusz] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Baltaziak, Marek] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Sulkowski, Stanislaw] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
RP Sulkowski, S (reprint author), Medical University of Bialystok, Department of General Pathomorphology, 15-269 Bialystok, Poland.
EM sulek@zeus.amb.edu.pl
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Surmacz E and Bartucci M: Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer. J Exp Clin Cancer Res 23: 385-394, 2004.
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Somasundar P, Yu AK, Vona-Davis and McFadden DW: Differential effects of leptin on cancer in vitro. J Surg Res 113: 50- 55, 2003.
Caldefie-Chezet F, Damez M, de Latour M, et al: Leptin: A proliferative factor for breast cancer? Study on human ductal carcinoma. Biochem Biophys Res Commun 334: 737-741, 2005.
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Sauter ER, Garofalo C, Hewett J, et al: Leptin expression in breast nipple aspirate fluid, NAF, and serum is influenced by body mass index, BMI, but not by the presence of breast cancer. Horm Metab Res 36: 336-340, 2004.
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Catalano S, Mauro L, Marsico S, et al: Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. J Biol Chem 279: 19908-19915, 2004.
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Laud K, Gourdou I, Pessemesse L, et al: Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol 188: 219- 226, 2002.
Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, et al: Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293: 622-628, 2002.
Magoffin DA, Weitsman SR, Aagarwal SK and Jakimiuk AJ: Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. Ginekol Pol 70: 1-7, 1999.
Garofalo C, Sisci D and Surmacz E: Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells. Clin Cancer Res 10: 6466-6475, 2004.
Nunez NP, Jelovac D, Macedo L, et al: Effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on serum hormones and bone characteristics in a preclinical tumor model for breast cancer. Clin Cancer Res 10: 5375-5380, 2004.
Cleary MP, Juneja SC, Phillips FC, et al: Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db, female mice do not develop oncogene-induced mammary tumors. Exp Biol Med 229: 182-193, 2004.
Coskun U, Gunel N, Toruner FB, et al. Serum leptin, prolactin and vascular endothelial growth factor, VEGF, levels in patients with breast cancer. Neoplasma 50: 41-46, 2003.
Ozet A, Arpaci F, Yilmaz MI, et al. Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol 31: 424-427, 2001.
Marttunen MB, Andersson S, Hietanen P, et al. Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients. Maturitas 35: 175-179, 2000.
Gunel N, Coskun U, Toruner FB, et al: Serum leptin levels are associated with tamoxifen-induced hepatic steatosis. Curr Med Res Opin 19: 47-50, 2003.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 69
EP 72
PG 4
ER
PT J
AU Szekely, E
Torok, V
Szekely, T
Riesz, P
Romics, I
AF Szekely, Eszter
Torok, Virag
Szekely, Tamas
Riesz, Peter
Romics, Imre
TI E-Cadherin Expression in Transitional Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bladder cancer; E-cadherin; transitional cell carcinoma
ID bladder cancer; E-cadherin; transitional cell carcinoma
AB The authors analyzed the expression of E-cadherin, one of the most important cell adhesion molecules, on histological slides of tumors of bladder cancer patients. The aim of the study was to see whether there is any association between E-cadherin expression and tumor grade, stage, age and gender of the patients, number of recurrences, or overall survival. The samples were examined in 51 primary bladder transitional cell carcinomas (TCC) of 50 patients, resected by transurethral resection (TUR) between January 1, 1996 and January 1, 1997. Immunoreactions were performed with monoclonal anti-human E-cadherin antibody. Forty of the fifty patients could be clinically followed. The analysis of the results on these forty patients was performed by contingency analysis and significance was assessed by ?2 test. No significant association between E-cadherin expression and tumor grade, stage, age or gender of the patients, the number of recurrences, or overall survival could be seen.
C1 [Szekely, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Torok, Virag] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Szekely, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Riesz, Peter] Semmelweis University, Department of UrologyBudapest, Hungary.
[Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
RP Szekely, E (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM szeszter@gmail.com
CR Acs G, LiVolsi VA: Loss of membrane expression of E-cadherin in leukemic erythroblasts. Arch Pathol Lab Med 125:198–201, 2001
Bringuier PP, Giroldi LA, Umbas R et al: Mechanisms associated with abnormal E-cadherin immunoreactivity in human bladder tumors. Int J Cancer 83: 591-595, 1999
Bringuier PP, Umbas R, Schaafsma HE et al: Decreased E-cadherin immunoreactivity correlates with poor survival inpatients with bladder tumors. Cancer Res 53: 3241-3245, 1993
Conacci-Sorrell M, ZhurinskyJ, Ben-Ze’ev A.: The cadherincatenin adhesion system in signaling and cancer. J Clin Invest 109:987-991, 2002
Fearon ER.: Connecting estrogen receptor function, transcriptional repression, and E-cadherin expression in breast cancer. Cancer Cell 3: 307-310, 2003
Giroldi LA, Bringuier PP, Shimazu T et al: Changes in cadherin- catenin complexes in the progression of human bladder carcinoma. Int J Cancer 82: 70-76, 1999
Han AC, Soler AP, Tang CK et al: Nuclear localization of Ecadherin expression in Merkel cell carcinoma. Arch Pathol Lab Med 124: 1147–1151, 2004
Handschuh G, Candidus S, Luber et al: Tumour-associated Ecadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility Oncogene 18:4301- 4312, 1999
Horikawa Y, Sugano K, Shigyo M et al: Hypermethylation of an E-cadherin, CDH1, promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ. J Urol 169:1541-1545, 2003
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Koksai IT, Ates M, Danisman A et al: Reduced E-cadherin and a-catenin expressions have no prognostic role in bladder carcinoma. Pathol Oncol Res 12: 13-19, 2006
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Mialhe A, Louis J, Pasquier D et al: Expression of E-cadherin and alpha-, beta-, and gamma-catenins in human bladder carcinomas: are they good prognostic factors? Invasion Metastasis 17: 124-137, 1997
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Yoo J, Park S, Kang CS et al: Expression of E-cadherin and p53 proteins in human soft tissue sarcomas. Arch Pathol Lab Med 1261: 33-38, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 73
EP 77
PG 5
ER
PT J
AU Baccar Harrath, A
Yacoubi Loueslati, B
Troudi, W
Hmida, S
Sedkaoui, S
Dridi, A
Jridi, A
Ben Ayed, F
Ben Rhomdhane, K
Ben Ammar Elgaaied, A
AF Baccar Harrath, Amal
Yacoubi Loueslati, Besma
Troudi, Wafa
Hmida, Slama
Sedkaoui, Syrine
Dridi, Amel
Jridi, Afef
Ben Ayed, Farhat
Ben Rhomdhane, Khaled
Ben Ammar Elgaaied, Amel
TI HLA Class II Polymorphism: Protective or Risk Factors to Breast Cancer in Tunisia?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HLA; DRB1; DQB1; breast cancer
ID HLA; DRB1; DQB1; breast cancer
AB HLA system plays a key role in the tumor cells' escape from immune surveillance. Herein is the first report on the correlation of the susceptibility to breast cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and -DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele and haplotype distribution between patients and 70 female control subjects reveals a negative association between HLADRB1* 07-DQB1*02 and the incidence of breast cancer in the Tunisian population.
C1 [Baccar Harrath, Amal] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
[Yacoubi Loueslati, Besma] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
[Troudi, Wafa] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
[Hmida, Slama] Tunisian Center of Blood TransfusionTunis, Tunisia.
[Sedkaoui, Syrine] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
[Dridi, Amel] Tunisian Center of Blood TransfusionTunis, Tunisia.
[Jridi, Afef] Tunisian Center of Blood TransfusionTunis, Tunisia.
[Ben Ayed, Farhat] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Ben Rhomdhane, Khaled] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Ben Ammar Elgaaied, Amel] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
RP Baccar Harrath, A (reprint author), University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 1060 Tunis, Tunisia.
EM amal.baccar@laposte.net
CR Abrahamova J, Majsky A: HLA system and some neoplastic diseases. Acta Univ Carol Med Monogr 123: 1-80, 1988
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Bidwell JL, Soong TW, Raymond PA, et al: HLA genotyping of colorectal carcinoma in the Chinese population. Hum Immunol 34:19- 23, 1992
Biswal BM, Kumar R, Julka PK, et al: Human leucocytic antigens, HLA, in breast cancer. Int J Med Sci 52:177-183, 1998
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Bouillence C, Deneufbourg JM: Positive correlation between breast cancer incidence and HLA antigens. Oncology 36:156-159, 1979
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Chaudhuri S, Cariappa A, Tang M, et al: Genetic susceptibility to breast cancer, HLA DQB*03032 and HLA DRB1*11 may represent protective alleles. Proc Natl Acad Sci USA 97: 11451-11454, 2000
De Jong MM, Nolte IM, De Vries EGE, et al: The HLA class III subregion is responsible for an increased breast cancer risk. Hum Mol Genet 12:2311-2319, 2003
Feinmesser M, Sulkes A, Morgenstern S, et al: HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities. J Clin Pathol 53: 286-291, 2000
Ferguson TA, Green DR, Griffith TS: Cell death and immune privilege. Int Rev Immunol 21:153-172, 2002
Ghaderi A, Talei A, Gharesi-Fard B, et al: HLA-DRB1 alleles and the susceptibility of Iranian patients with breast cancer. Pathol Oncol Res 7: 39-41, 2001
Hammond MG, Appadoo B, Brain P: HLA and cancer in South African Indians. Tissue Antigens 14:296-302, 1979
Hmida S, Gauthier A, Dridi A, et al: HLA class II polymorphism in Tunisians. Tissue Antigens 45: 63-68, 1995
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Park KS, Mok JW, Ko HE, et al: Polymorphisms of tumor necrosis factors A and B in breast cancer. Eur J Immunogenet 29: 7-10, 2002
Pellegris G, Illeni MT, Vaglini M, et al: HLA antigens in malignant melanoma patients. Tumori 66: 51-58, 1980
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Subira ML, Crisci CD, Zornoza G, et al: Breast cancer and histocompatibility antigens. Allegrol Immunopathol, Madr, 7: 411-416, 1979
Wu MS, Hsieh RP, Huang SP, et al: Association of HLA-DQB1*0301 and HLA-DQB1*0602 with different subtypes of gastric cancer in Taiwan. Jpn J Cancer Res 93:404-410, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 79
EP 81
PG 3
ER
PT J
AU Sughayer, AM
Al-Khawaja, MM
Massarweh, S
Al-Masri, M
AF Sughayer, A Maher
Al-Khawaja, M Maha
Massarweh, Suleiman
Al-Masri, Mahmoud
TI Prevalence of Hormone Receptors and HER2/neu in Breast Cancer Cases in Jordan
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; hormone receptors; HER2/neu
ID breast cancer; hormone receptors; HER2/neu
AB The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the expression of these receptors is well documented. The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types. A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004. Standard immune stains were used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were ductal carcinomas of various histological grades, 122 (50.8%) of which were ER-positive, 138 (57.5%) PRpositive and 42 (17.5%) HER2/neu-positive. Twentytwo (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive, 20 (90.9%) PRpositive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).
C1 [Sughayer, A Maher] King Hussein Cancer Center, Department of Pathology, Queen Rania AlAbdullah Str., 11941 Amman, Jordan.
[Al-Khawaja, M Maha] King Hussein Cancer Center, Department of Pathology, Queen Rania AlAbdullah Str., 11941 Amman, Jordan.
[Massarweh, Suleiman] Department of Medical OncologyAmman, Jordan.
[Al-Masri, Mahmoud] Department of Surgical OncologyAmman, Jordan.
RP Sughayer, AM (reprint author), King Hussein Cancer Center, Department of Pathology, 11941 Amman, Jordan.
CR Lazennec G, Bresson D, Lucas A, et al: ER beta inhibits proliferation and invasion of breast cancer cells. Endocrinology 142: 4120-4130, 2001
Anderson E, Clarke RB, Howell A: Estrogen responsiveness and control of normal human breast proliferation. Review. J Mammary Gland Biol Neoplasia 3: 23-35, 1998
Osborne CK, Yochmowitz MG, Knight WA 3rd, McGuire WL: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46: 2884-2888, 1980
Wittliff JL: Steroid-hormone receptors in breast cancer. Cancer 53, 3 Suppl): 630-643, 1984
Slamon DJ, Clark GM, Wong SG, et al: Human breast cancer: correlation of relapse and survival with amplification of the HER- 2/neu oncogene. Science 235: 177-182, 1987
Shak S: Overview of the trastuzumab, Herceptin, anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Review. Semin Oncol 4 Suppl 12: 71-77, 1999
Cobleigh MA, Vogel CL, Tripathy D, et al: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 9: 2639-2648, 1999
Tavassoli FA, Devilee P, Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press: Lyon, 2003
Pegoraro RJ, Karnan V, Nirmul D, Joubert SM: Estrogen and progesterone receptors in breast cancer among women of different racial groups. Cancer Res 46: 2117-2120, 1986
Ruder AM, Lubin F, Wax Y, et al: Estrogen and progesterone receptors in breast cancer patients. Epidemiologic characteristics and survival differences. Cancer 64: 196-202, 1989
Gapstur SM, Dupuis J, Gann P, et al: Hormone receptor status of breast tumors in black, Hispanic, and non-Hispanic white women. An analysis of 13,239 cases. Cancer 77: 1465-71, 1996
Joslyn SA: Hormone receptors in breast cancer: racial differences in distribution and survival. Breast Cancer Res Treat 73: 45-59, 2002
Li CI, Malone KE, Daling JR: Differences in breast cancer hormone receptor status and histology by race and ethnicity among women 50 years of age and older. Cancer Epidemiol Biomarkers Prev 7: 601-607, 2002
Chu KC, Anderson WF, Fritz A, et al: Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups. Cancer 92: 37-45, 2001
Stierer M, Rosen H, Weber R, et al: Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. Correlation of histopathology and prognostic factors. Ann Surg 218: 13-21, 1993
Chow LW, Ho P: Hormonal receptor determination of 1,052 Chinese breast cancers. J Surg Oncol 75: 172-175, 2000
Lertsanguansinchai P, Chottetanaprasith T, Chatamra K, et al: Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at King Chulalongkorn Memorial Hospital. J Med Assoc Thai 85, Suppl 1: S193-202, 2002
Ikpatt OF, Ndoma-Egba R: Oestrogen and progesterone receptors in Nigerian breast cancer: relationship to tumour histopathology and survival of patients. Cent Afr J Med 49: 122-126, 2003
al-Alwan NA, al-Kubaisy W, al-Rawaq K: Assessment of response to tamoxifen among Iraqi patients with advanced breast cancer. East Mediterr Health J 6: 475-82, 2000
Abadjian G, Antoun R: Breast carcinoma: evaluation of hormone receptors and pS2, erb-B2, P-glycoprotein and Ki-67 markers. J Med Liban 44: 10-15. 1996 in French
Samir S Amr, Abdul Rahman M. Sa'di, Fazal Ilahi, et al: Spectrum of Breast Diseases In Saudi Arab Females: A 26 Year Pathological Survey At Dhahran Health Center. Ann Saudi Med 15: 125-132, 1995
McCarthy NJ, Yang X, Linnoila IR, et al: Microvessel density, expression of estrogen receptor alpha, MIB-1, p53, and c-erbB-2 in inflammatory breast cancer. Clin Cancer Res 8: 3857-3862, 2002
Arpino G, Bardou VJ, Clark GM, Elledge RM: Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 6: 149-156, 2004
Ross JS, Fletcher JA: HER-2/neu, c-erb-B2, gene and protein in breast cancer. Am J Clin Pathol 112(Suppl 1): S53-67, 1999
Ameyaw MM, Tayeb M, Thornton N, et al: Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer. J Hum Genet 47: 172-175, 2002
Sellami M, Gamoudi M, Krichen K, et al: Incidence of amplification of the C-erb B2/Her-2/neu gene in human breast cancer, in French). Arch Inst Pasteur Tunis 68: 33-41, 1991
el-A Helal T, Khalifa A, Kamel AS: Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in Egypt. Anticancer Res 20: 2145-2150, 2000
Middleton LP, Palacios DM, Bryant BR, Krebs P, Otis CN, Merino MJ: Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol 24: 1650-1656, 2000
Feuer EJ, Wun LM: DEVCAN: Probability of Developing or Dying of Cancer. Version 4.0. Bethesda MD: National Cancer Institute. 1999.
Al-Kayed S, Al-Hijawi B, Al-Haliq T: Incidence of cancer in Jordan 2001. National Cancer Registry, Ministry of Health/Jordan, 2001
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 83
EP 86
PG 4
ER
PT J
AU Hiraishi, Y
Wada, T
Nakatani, K
Negoro, K
Fujita, Sh
AF Hiraishi, Yukihiro
Wada, Takeshi
Nakatani, Ken
Negoro, Kenji
Fujita, Shigeyuki
TI Immunohistochemical Expression of EGFR and p-EGFR in Oral Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; p-EGFR; oral squamous cell carcinomas
ID EGFR; p-EGFR; oral squamous cell carcinomas
AB Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family, which is expressed or highly expressed in a variety of solid tumors, including oral cancers. High EGFR expression has been correlated with tumor size, metastasis and survival. In recent years, EGFR has been considered a promising target for monoclonal antibody therapy. A total of 52 patients with oral squamous cell carcinoma (OSCC) were selected for EGFR and phosphorylated EGFR (p-EGFR) detection. Immunohistochemical staining was performed to evaluate EGFR and p-EGFR expression. Positive EGFR and p-EGFR staining was present in 92.3% (48/52) and 98.0% (51/52) of all cases, respectively. High EGFR and p-EGFR expression was present in 63.4% (33/52) and 69.2% (36/52) of all cases, respectively. EGFR and p-EGFR expression did not correlate with the clinical factors tumor stage, regional lymph node metastasis, or distant metastasis. However, a statistically significant correlation was identified between high EGFR expression and the pathologic factor tumor invasion. As a conclusion, the majority of OSCCs highly express EGFR and p-EGFR, indicating the importance of studying the efficacy of anticancer therapy targeting these signal factors.
C1 [Hiraishi, Yukihiro] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 kimiidera, 641-8509 Wakayama, Japan.
[Wada, Takeshi] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 kimiidera, 641-8509 Wakayama, Japan.
[Nakatani, Ken] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 kimiidera, 641-8509 Wakayama, Japan.
[Negoro, Kenji] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 kimiidera, 641-8509 Wakayama, Japan.
[Fujita, Shigeyuki] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 kimiidera, 641-8509 Wakayama, Japan.
RP Hiraishi, Y (reprint author), Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 641-8509 Wakayama, Japan.
EM hiraishi@wakayama-med.ac.jp
CR Salomon DS, Brandt R, Ciardiello F, Normanno N: Epidermal growth factor- related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19: 183-232, 1995
Mendelsohn J, Baselga L: Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 14: 2787- 2799, 2003
Irish JC, Bernstein A: Oncogenes in head and neck cancer. Laryngoscope 103: 42-52, 1993
Yamamoto E, Kohama G, Iwai M, Hiratsuka H: Mode of invasion, Bleomycin sensitivity and clinical course in squamous cell carcinoma of the oral cavity. Cancer 51: 2175-2180, 1983
Wada T: Nature of mononuclear cell infiltrates in oral squamous cell carcinoma and their clinical significance. Wakayama Med Rep 30: 103-117, 1989
Putti TC, To KF, Hsu HC, et al: Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia-Pacific region. Histopathology 41: 144-151, 2002
van Oijen MG, Rijksen G, ten Broek FW, Slootweg PJ: Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse. Oral Dis 4: 4-8, 1998
Wen QH, Nishimura T, Nagayama I, Furukawa M: Expression of EGF, EGFR and PCNA in laryngeal lesions. J Laryngol Otol 109: 630-636, 1995
Lee CS, Redshaw A, Boag G: Epidermal growth factor immunoreactivity in human laryngeal squamous cell carcinoma. Pathology 29: 251-254, 1997
Kearsley JH, Leonard JH, Walsh MD, Wright GR: A comparison of epidermal growth factor receptor, EGFR, and c-erbB-2 oncogene expression in head and neck squamous cell carcinomas. Pathology 23: 189-194, 1991
Zheng X, Hu L, Chen F, Christensson B: Expression of Ki67 antigen, epidermal growth factor receptor and Epstein-Barr virus-encoded latent membrane protein, LMP1, in nasopharyngeal carcinoma. Eur J Cancer B Oral Oncol 30: 290-295, 1994
Miyaguchi M, Olofsson J, Hellquist HB: Expression of epidermal growth factor receptor in glottic carcinoma and its relation to recurrence after radiotherapy. Clin Otolaryngol 16: 466-469, 1991
Downward J, Parker P, Waterfield MD: Autophosphorylation sites on the epidermal growth factor receptor. Nature 311: 483-485, 1984
Kanematsu T, Yano S, Uehara H, et al: Phosphorylation, but not overexpression, of epidermal growth factor receptor is associated with poor prognosis of non-small cell lung cancer patients. Oncol Res 13: 289-298, 2003
Olayioye MA, Neve RM, Lane HA, Hynes NE: The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J 19: 3159-3167, 2000
Kolch W: Meaningful relationships: The regulation of the Ras/Raf/MEK/ ERK pathway by protein interactions. Biochem J 351: 289-305, 2000
Zwick E, Bange J, Ullrich A: Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med 8: 17-23, 2002
Busse D, Doughty RS, Ramsey TT, et al: Reversible G1 arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27KIP1 independent of MAPK activity. J Biol Chem 275: 6987-6995, 2000
Khazaie K, Schirrmacher V, Lichtner RB: EGF receptor in neoplasia and metastasis. Cancer Metastasis Rev 12: 255-274, 1993
Storkel S, Reichert T, Reiffen KA, Wagner W: EGFR and PCNA expression in oral squamous cell carcinomas–a valuable tool in estimating the patient’s prognosis. Eur J Cancer B Oral Oncol 29: 273-277, 1993
Xia W, Lau YK, Zhang HZ, et al: Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res 5: 4164- 4174, 1999
Christensen ME: The EGF receptor system in head and neck carcinomas and normal tissues. Immunohistochemical and quantitative studies. Dan Med Bull 45:121-134, 1998
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 87
EP 91
PG 5
ER
PT J
AU Kahan, Zs
Varga, K
Dudas, R
Nyari, T
Thurzo, L
AF Kahan, Zsuzsanna
Varga, Katalin
Dudas, Rita
Nyari, Tibor
Thurzo, Laszlo
TI Collaborative/Active Participation per se Does Not Decrease Anxiety in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE anxiety; early breast cancer; information needs; metastatic breast cancer; treatment decision-making
ID anxiety; early breast cancer; information needs; metastatic breast cancer; treatment decision-making
AB The information needs of breast cancer patients on their disease, its treatment, the prognosis, and their attitude to decision-making concerning treatment were assessed. One hundred and fifty early and 45 metastatic breast cancer patients were recruited into the study. The amount of information and role in the treatment decision-making process preferred by the patient were independently estimated by the patient and the oncologist, using questionnaires. Information was provided in accordance with the wishes of the patient as perceived by the physician. Test of anxiety was performed before, and one week after the consultation. Most of the patients claimed to anticipate the provision of extensive information and an active role in the decision-making, but real interest during the consultation was found less frequently. The post-consultation anxiety test revealed a significant decrease in situational anxiety; this was not related to the patient’s information needs or her attitude to the decision-making concerning treatment. Our study demonstrates that a significant decrease in anxiety may be achieved via a consultation tailored to the needs of the patient. Loading the patient with information and involvement in the decision regarding therapy as much as the patient seems comfortable with lowers distress.
C1 [Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., H-6720 Szeged, Hungary.
[Varga, Katalin] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., H-6720 Szeged, Hungary.
[Dudas, Rita] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., H-6720 Szeged, Hungary.
[Nyari, Tibor] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., H-6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM kahan@onko.szote.u-szeged.hu
CR Holland JC: IPOS Sutherland Memorial Lecture: an international perspective on the development of psychosocial oncology: overcoming cultural and attitudinal barriers to improve psychosocial care. Psychooncology 13: 445-459, 2004
Ruckdeschel JC, Blanchard CG, Albrecht T: Psychosocial oncology research. Where we have been, where we are going, and why we will not get there. Cancer 74(suppl 4): S1458- S1463, 1994
The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. A Canadian consensus document. CMAJ 158(suppl 3): S3-S64, 1998
Coates A: Management of early breast cancer: An Australian consensus report. Oncology 52: 82-85, 1995
Fallowfield LJ, Hall A, Maguire GP, et al: Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. BMJ 301: 575-580, 1990
Brown RF, Butow PN, Dunn SM, et al: Promoting patient participation and shortening cancer consultations: a randomised trial. Br J Cancer 85: 1273-1279, 2001
Siminoff LA, Ravdin P, Colabianchi N, et al: Doctor-patient communication patterns in breast cancer adjuvant therapy discussions. Health Expect 3: 26-36, 2000
Wallberg B, Michelson H, Nystedt M, et al.: Information needs and preferences for participation in treatment decisions among Swedish breast cancer patients. Acta Oncol 39: 467-476, 2000
Hagerty RG, Butow PN, Ellis PA, et al: Cancer patient preferences for communication of prognosis in the metastatic setting. J Clin Oncol 22: 1721-1730, 2004
Bruera E, Sweeney C, Calder K, et al: Patient preferences versus physician perceptions of treatment decisions in cancer care. J Clin Oncol 19: 2883-2885, 2001
Blanchard CG, Labrecque MS, Ruckdeschel JC, et al: Physician behaviors, patient perceptions, and patient characteristics as predictors of satisfaction of hospitalized adult cancer patients. Cancer 65: 186-192, 1990
Jansen SJ, Otten W, van de Velde CJ, et al: The impact of the perception of treatment choice on satisfaction with treatment, experienced chemotherapy burden and current quality of life. Br J Cancer 91: 56-61, 2004
Mesters I, van den Borne B, De Boer M, et al: Measuring information needs among cancer patients. Patient Educ Cons 43: 253-262, 2001
Spielberger CD: Manual for the state trait anxiety inventory, Form Y). Consulting Psychologists Press, Palo Alto, CA, 1983
Degner LF, Sloan JA: Decision making during serious illness: what role do patients really want to play? J Clin Epidemiol 45: 941-950, 1992
Ravdin PM, Siminoff LA, Davis GJ, et al: Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19: 980-991, 2001
Whelan T, Sawka C, Levine M, et al: Helping patients make informed choices: a randomized trial of a decision aid for adjuvant chemotherapy in lymph node-negative breast cancer. J Natl Cancer Inst 95: 581-587, 2003
Whelan T, Levine M, Willan A, et al: Effect of a decision aid on knowledge and treatment decision making for breast cancer surgery: a randomized trial. JAMA 292: 435-441, 2004
Beaver K, Bogg J, Luker KA: Decision-making role preferences and information needs: a comparison of colorectal and breast cancer. Health Expect 2: 266-276, 1999
Beaver K, Luker KA, Owens RG, et al: Treatment decision making in women newly diagnosed with breast cancer. Cancer Nurs 19:8-19, 1996
Butow PN, Dunn SM, Tattersall MHN, et al: Patient participation in the cancer consultation: evaluation of a question prompt sheet. Ann Oncol 5: 199-204, 1994
Butow PN, Kazemi JN, Beeney LJ, et al.: When diagnosis is cancer. Patient communication experiences and preferences. Cancer 77: 2630-2637, 1996
Moumjid N, Carrere MO, Charavel M, et al: Clinical issues in shared decision-making applied to breast cancer. Health Expect 6: 222-227, 2003
Lam W, Fielding R, Chan M, et al: Participation and satisfaction with surgical treatment decision-making in breast cancer among Chinese women. Breast Cancer Res Treat 80: 171-180, 2003
Cassileth BR, Zupkis RV, Sutton-Smith K, et al: Information and participation preferences among cancer patients. Ann Int Med 92:832-836, 1980
Bilodeau BA, Degner LF: Information needs, sources of information, and decisional roles in women with breast cancer. Oncol Nurs Forum 23:691-696, 1996
Johnson JD, Roberts CS, Cox CE, et al: Breast cancer patients’ personality style, age, and treatment decision making. J Surg Oncol 63:183-186, 1996
Maly RC, Umezawa Y, Leake B, et al: Determinants of participation in treatment decision-making by older breast cancer patients. Breast Cancer Res Treat 85: 201-209, 2004
Sepucha KR, Belkora JK, Tripathy D, et al: Building bridges between physicians and patients: results of a pilot study examining new tools for collaborative decision making in breast cancer. J Clin Oncol 18: 1230-1238, 2000
Liang W, Burnett CB, Rowland JH, et al: Communication between physicians and older women with localized breast cancer: implication for treatment and patient satisfaction. J Clin Oncol 20: 1008-1016, 2002
Bruera E, Willey JS, Palmer JL, et al: Treatment decisions for breast carcinoma: patient preferences and physician perceptions. Cancer 94: 2076-2080, 2002
Leighl N, Gattellari M, Butow P, et al: Discussing adjuvant cancer therapy. J Clin Oncol 19: 1768-1778, 2001
Butow PN, Dowsett S, Hagerty R, et al: Communicating prognosis to patients with metastatic disease: what do they really want to know? Support Care Cancer 10: 161-168, 2002
Janz NK, Wren PA, Copeland LA, et al: Patient-physician concordance: preferences, perceptions, and factors influencing the breast cancer surgical decision. J Clin Oncol 22: 3091-3098, 2004
Protiere C, Viens P, Genre D, et al: Patient participation in medical decision-making: a French study in adjuvant radiochemotherapy for early breast cancer. Ann Oncol 11: 39-45, 2000
Molenaar S, Sprangers MA, Rutgers EJ, et al: Decision support for patients with early-stage breast cancer: effects of an interactive breast cancer CDROM on treatment decision, satisfaction, and quality of life. J Clin Oncol 19: 1676-1687, 2001
EUSOMA Position Paper. The requirements of a special breast unit. Eur J Cancer 36: 2288-2293, 2000
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 93
EP 101
PG 9
ER
PT J
AU Borka, K
Patai, K
Rendek, A
Sobel, G
Paulin, F
AF Borka, Katalin
Patai, Kalman
Rendek, Aniko
Sobel, Gabor
Paulin, Ferenc
TI Pleomorphic Rhabdomyosarcoma of the Uterus in a Postmenopausal Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE pleomorphic rhabdomyosarcoma; uterus; adult; immunohistochemistry; postmenopausal bleeding
ID pleomorphic rhabdomyosarcoma; uterus; adult; immunohistochemistry; postmenopausal bleeding
AB Pure rhabdomyosarcomas occurring in the adult uterus are very rare, with poor prognosis. We present a case of a 67-year-old woman with postmenopausal vaginal bleeding caused by pleomorphic rhabdomyosarcoma of the uterus, treated with hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy and partial sigmoidectomy. Postoperative chemotherapy (Doxorubicin) was given according to protocol. Follow-up examinations one year after surgery revealed no abnormalities or tumor recurrence. The rarity of this histological entity makes the presented case worthy of publication.
C1 [Borka, Katalin] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Patai, Kalman] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Rendek, Aniko] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Paulin, Ferenc] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
RP Borka, K (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM bk@korb2.sote.hu
CR Holcomb K, Francis M, Ruiz J, et al: Pleomorphic rhabdomyosarcoma of the uterus in a postmenopausal woman with elevated serum CA-125. Gynecol Oncol 74: 499-501, 1999
Chiarle R, Godio L, Fusi D, et al: Pure alveolar rhabdomyosarcoma of the corpus uteri: description of a case with increased serum level of CA-125. Gynecol Oncol 66: 320-323, 1997
Sternberg SS, ed.): Diagnostic Surgical Pathology. Raven Press, New York, 1989
Rosai J, ed.): Rosai and Ackerman’s Surgical Pathology. Mosby, Edinburgh, 2004
Kulka EW, Douglas GW: Rhabdomyosarcoma of the corpus uteri: report of a case, associated with adenocarcinoma of the cervix, with review of the literature. Cancer 5: 727-736, 1952
McCluggage WG, Lioe TF, Mcclelland HR, et al: Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant. Gynecol Oncol 12: 128-132, 2002
Podczaski E, Sees J, Kaminski P, et al: Rhabdomyosarcoma of the uterus in a postmenopausal patient. Gynecol Oncol 37: 439- 442, 1990
Ng TY, Loo KT, Leung TW, et al: Alveolar rhabdomyosarcoma of the cervix. Gynecol Oncol 91: 623-626, 2003
Hart WR, Craig JR: Rhabdomyosarcomas of the uterus. Am J Clin Pathol 70: 217-223, 1987
Cavazzana AO, Schmidt D, Ninfo V, et al: Spindle cell rhabdomyosarcoma: a prognostically favorable variant of rhabdomyosarcoma. Am J Surg Pathol 16: 229-235, 1992
Montag TW, D’ablaing G, Schlaerth JB, et al: Embryonal rhabdomyosarcoma of the uterine corpus and cervix. Gynecol Oncol 25: 171-194, 1986
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 102
EP 104
PG 3
ER
PT J
AU Dundar, E
Acikalin, FM
Can, C
AF Dundar, Emine
Acikalin, Fuat Mustafa
Can, Cavit
TI The Nested Variant of Urothelial Carcinoma: an Aggressive Tumor Closely Simulating Benign Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE urothelial carcinoma; nested variant
ID urothelial carcinoma; nested variant
AB The ''nested'' variant is a rare form of urothelial carcinoma and its biologic behavior is highly aggressive. Herein two new cases of nested variant of urothelial carcinoma with immunohistochemical examination are presented. In one of the cases, the tumor extended through the bladder wall into the perivesicular soft tissue, prostatic urethra and left vesicula seminalis, and metastasized to obturator lymph nodes. In the other case, invasion of muscular layer was observed and three recurrences were developed during a follow-up period of 23 months. Both tumors of our study demonstrated high p53 and Ki-67 indices, supporting the aggressive nature of such tumors.
C1 [Dundar, Emine] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Fakultesi Patoloji Anabilim DaliEskisehir, Turkey.
[Acikalin, Fuat Mustafa] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Fakultesi Patoloji Anabilim DaliEskisehir, Turkey.
[Can, Cavit] Eskisehir Osmangazi University, Faculty of Medicine, Department of UrologyEskisehir, Turkey.
RP Dundar, E (reprint author), Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Eskisehir, Turkey.
EM edundar_99@yahoo.com
CR Talbert ML, Young RH: Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases. Am J Surg Pathol 13: 374-381, 1989
Lin O, Cardillo M, Dalbagni G, et al: Nested variant of urothelial carcinoma: A clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol 16: 1289-1298, 2003
Murphy WM, Deana DG: The nested variant of transitional cell carcinoma: A neoplasm resembling proliferation of Brunn’s nests. Mod Pathol 5: 240-243, 1992
Xiao GQ, Savage SJ, Gribetz ME, et al: The nested variant of urothelial carcinoma. Clinicopathology of 2 cases. Arch Pathol Lab Med 127: 333-336, 2003
Holmang S, Johansson SL: The nested variant of transitional cell carcinoma. A rare neoplasm with poor prognosis. Scand J Urol Nephrol 35:102-105, 2001
Volmar KE, Chan TY, De Marzo AM, Epstein JI: Florid von Brunn nests mimicking urothelial carcinoma. A morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Am J Surg Pathol 27: 1243-1252, 2003
Drew PA, Furman J, Civantos F, Murphy WM: The nested variant of transitional carcinoma: an aggressive neoplasm with innocuous histology. Mod Pathol 9: 989-994, 1996
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 105
EP 107
PG 3
ER
PT J
AU Glisic, A
Atanackovic, J
AF Glisic, Andreja
Atanackovic, Jasmina
TI Krukenberg tumor in pregnancy. The lethal outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Krukenberg tumor; pregnancy; lethal outcome
ID Krukenberg tumor; pregnancy; lethal outcome
AB Krukenberg tumor refers to gastrointestinal cancer metastatic to the ovaries and its prognosis is uniformly poor. This case report concerns a 38-year-old pregnant woman suffering from abdominal pain and iterative vomiting episodes. She presented with a large abdominopelvic tumor. Because of suspected ovarian torsion, we performed urgent surgery. At laparotomy, bilateral ovarian tumors, ascites and gastric cancer located at the cardia and the lesser curvature invading the serosa were identified. We performed right ovariectomy, resection of the left ovary, and gastric biopsy. Histological examination of the specimen yielded diagnosis of Krukenberg tumor. Ten days later the patient underwent an elective Cesarean section in the 25th gestational week because of fetal asphyxia and very poor maternal life prognosis. We performed Cesarean delivery and extracted a vital female newborn of 31 cm, 600 g, Ap score 3, with virilization. Few days later the baby died at the intensive care unit. Two weeks later the mother died because of pulmonary failure.
C1 [Glisic, Andreja] Clinical Center of Serbia, Department of Obstetrics and Gynecology, Visegradska 26, 11000 Belgrade, Serbia.
[Atanackovic, Jasmina] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
RP Glisic, A (reprint author), Clinical Center of Serbia, Department of Obstetrics and Gynecology, 11000 Belgrade, Serbia.
EM gan@eunet.yu
CR McGill F, Ritter DB, Rickard C, et al: Management of Krukenberg tumors: an 11-year experience and review of the literature. Prim. Care Update Ob Gyns 5:157-158, 1998
McGill F, Ritter DB, Rickard C, et al: Krukenberg tumors: can management be improved? Gynecol Obstet Invest 48: 61-65, 1999
Agarwal N, Parul, Kriplani A, et al: Management and outcome of pregnancies complicated with adnexal masses. Arch Gynecol Obstet 267: 148-152, 2003
Chou MM, Ho ES, Lin NF, Lee YH: Color Doppler sonographic appearance of a Krukenberg tumor in pregnancy. Ultrasound Obstet Gynecol 11: 459-460, 1998
Mackey JR, Hugh J, Smylie M: Krukenberg tumor complicated by pregnancy. Gynecol Oncol 61: 153-155, 1996
De Palma P, Wronski M, Bifermino V, Bovani I: Krukenberg tumor in pregnancy with virilization. A case report. Eur J Gynaecol Oncol 16: 59-64, 1995
Tamussino K, Scholl W, Reich O, Winter R: Gastric carcinoma presenting as a Krukenberg tumor in the 24th week of gestation. Eur J Obstet Gynecol Reprod Biol 62: 251-252, 1995
Cheng CY, Chen TY, Lin CK, et al: Krukenberg tumor in pregnancy with delivery of a normal baby: a case report. Zhonghua Yi Xue Za Zhi, Taipei, 54: 424-427, 1994
Scharl A, Huber P, Lorenyen J, Gohring UJ: Gastric cancer during early pregnancy. Two case reports. Arch Gynecol Obstet 258: 151-154, 1996
Sandmaier D, Lobrinus JA, Vial Y, et al: Bilateral Krukenberg tumor of the ovary during pregnancy. Eur J Gynecol Oncol 21: 58-60, 2000
Cosme A, Ojeda E, Bujanda L, et al: Krukenberg tumor secondary to gastric carcinoma in a woman in her eighth month of pregnancy. Gastroenterol Hepatol 24: 63-65, 2001
Okutomi T, Hoshino Y, Amano K, et al: Intrathecal fentanyl/ meperidine combined with low-dose epidural bupivacaine for Cesarean section in a patient with advanced Krukenberg tumors. Acta Anaesthesiol Scand 46: 1272-1275, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 108
EP 110
PG 3
ER
PT J
AU Vargas-Gonzalez, R
Sanchez-Sosa, S
AF Vargas-Gonzalez, Roberto
Sanchez-Sosa, Sergio
TI Fibrocartilaginous Dysplasia (Fibrous Dysplasia with Extensive Cartilaginous Differentiation)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Fibrocartilaginous dysplasia; fibrous dysplasia; fibrochondrodysplasia; fibrous dysplasia with cartilaginous differentiation
ID Fibrocartilaginous dysplasia; fibrous dysplasia; fibrochondrodysplasia; fibrous dysplasia with cartilaginous differentiation
AB Fibrocartilaginous dysplasia is a variant of fibrous dysplasia in which extensive cartilaginous differentiation is identified. The amount of cartilage varies from case to case, however, no percentage has been proposed to consider this diagnosis. We present a 6-year-old girl with a two-year history of hip pain. Initial imaging studies of the right femur revealed a lucent lesion of the proximal shaft that extended into the femoral neck with ill-defined borders but wellmaintained cortex. Computed tomography scan demonstrated increased density of the medullary cavity but the cortex appeared intact. Curettage of the lesion was performed and fragments with cartilaginous appearance were obtained, weighing 45 g in total. Microscopically, the tumor revealed a cartilaginous (60%) and a fibro-osseous (40%) component; the former had increased cellularity and some chondrocytes displayed moderate atypia and binucleation, while the latter showed features of fibrous dysplasia. Areas of endochondral ossification and calcification were also identified. After five years of surgery this child is well and without evidence of recurrence. We discuss the differential diagnosis of this variant of fibrous dysplasia in the pediatric group.
C1 [Vargas-Gonzalez, Roberto] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla - Atlixco, 72190 Puebla, Mexico.
[Sanchez-Sosa, Sergio] Hospital Para el Nino Poblano, Department of Pathology, Km 1.5 Carretera Federal Puebla - Atlixco, 72190 Puebla, Mexico.
RP Vargas-Gonzalez, R (reprint author), Hospital Para el Nino Poblano, Department of Pathology, 72190 Puebla, Mexico.
EM soncoy@msn.com
CR Alman BA, Greel DA, Wolfe HJ: Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res 14: 311-315, 1996
Bianco P, Riminucci M, Majolagbe A, et al: Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res 15:120-128, 2000
Lichtenstein L, Jaffe HL: Fibrous dysplasia of bone. Arch Pathol 33: 777-816, 1942
Dorfman HD, Czeniak B: Bone Tumors. Mosby, St. Louis, 1998, pp. 441-481
Forest M, Tomeno B, Vanel D: Orthopedic surgical pathology: diagnosis of tumors and pseudotumoral lesions of bone and joints. Churchill Livingstone, Edinbourgh, 1998, pp. 595-612
Kransdorf MJ, Moser RP, Gilkey FW: Fibrous dysplasia. Radiographics 10: 519-537, 1990
Harris WH, Dudley HR Jr, Barry RJ: The natural history of fibrous dysplasia. J Bone Joint Surg Am 44:207-233, 1962
Sanerkin NG, Watt I: Enchondromata with annular calcification in association with fibrous dysplasia. B J Radiol 54: 1027- 1033, 1981
Pelzmann KS, Nagel DZ, Salyer WR: Case report 114. Skeletal Radiol 5:116-118, 1980
Drolshagen LF, Reynolds WA, Marcus NW: Fibrocartilaginous dysplasia of bone. Radiology 156: 32, 1985
Hermann G, Klein M, Abdelwahab IF, Kenan S: Fibrocartilaginous dysplasia. Skeletal Radiol 25: 509-511, 1996
Ishida T, Dorfman HD: Massive chondroid differentiation in fibrous dysplasia of bone, fibrocartilaginous dysplasia). Am J Surg Pathol 17: 924-930, 1993
De Smet AA, Travers H, Neff JR: Chondrosarcoma occurring in a patient with polyostotic fibrous dysplasia. Skeletal Radiol 7: 197-201, 1981
Teldorf ED: A case of osteitis fibrosa, with formation of hyaline cartilage). Br J Surg 18:409-414, 1930
Kyriakos M, Mc Donald DJ, Sundaram M: Fibrous dysplasia with extensive cartilaginous differentiation, “fibrocartilaginous dysplasia”): a review, with an illustrative case followed for 18 years. Skeletal Radiol 33: 51-62, 2004
Bulychova IV, Unni KK, Bertoni F, Beabout JW: Fibrocartilaginous mesenchymoma of bone. Am J Surg Pathol 17: 830-836, 1993
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 111
EP 114
PG 4
ER
PT J
AU Merkli, H
Pal, E
Gati, I
Czopf, J
AF Merkli, Hajnalka
Pal, Endre
Gati, Istvan
Czopf, Jozsef
TI Distal Myopathy with Rimmed Vacuoles and Cerebellar Atrophy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE ataxia; cerebellar atrophy; distal myopathy; rimmed vacuole
ID ataxia; cerebellar atrophy; distal myopathy; rimmed vacuole
AB Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.
C1 [Merkli, Hajnalka] University of Pecs, Department of Neurology, Ret u.2.,, H-7623 Pecs, Hungary.
[Pal, Endre] University of Pecs, Department of Neurology, Ret u.2.,, H-7623 Pecs, Hungary.
[Gati, Istvan] University of Pecs, Department of Neurology, Ret u.2.,, H-7623 Pecs, Hungary.
[Czopf, Jozsef] University of Pecs, Department of Neurology, Ret u.2.,, H-7623 Pecs, Hungary.
RP Pal, E (reprint author), University of Pecs, Department of Neurology, H-7623 Pecs, Hungary.
EM endre.pal@aok.pte.hu
CR Ikeuchi T, Asaka T, Saito M, et al: Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9. Ann Neurol 41: 432-437, 1997.
Kumamoto T, Fukuhara N, Nagashima M, et al: Distal myopathy. Histochemical and ultrastructural studies. Arch Neurol 39: 367-371, 1982.
Kumamoto T, Ito T, Horinouchi H, et al: Increased lysosomerelated proteins in the skeletal muscles of distal myopathy with rimmed vacuoles. Muscle Nerve 23: 1686-1693, 2000.
Mastaglia FL, Laing NG: Distal myopathies: clinical and molecular diagnosis and classification. J Neurol Neurosurg Psychiatry 67: 703-709, 1999.
Mizusawa H, Kurisaki H, Takatsu M, et al: Rimmed vacuolar distal myopathy: a clinical, electrophysiological, histopathological and tomographic study of seven cases. J Neurol 234: 129-136, 1987.
Mizusawa H, Kurisaki H, Takatsu M, et al: Rimmed vacuolar distal myopathy. An ultrastructural study. J Neurol 234: 137- 145, 1987.
Nishino I, Noguchi S, Murayama K, et al: Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy. Neurology 59: 1689-1693, 2002.
Nonaka I, Murakami N, Suzuki Y, et al: Distal myopathy with rimmed vacuoles. Neuromusc Disord 8: 333-337, 1998.
Sunohara N, Nonaka I, Kamei N, Satoyoshi E: Distal myopathy with rimmed vacuole formation. Brain 112: 65-83, 1989.
Werneck LC, Marrone CD, Scola RH: Distal myopathies: clinical, laboratory, electromyographic, histologic-histochemical analysis of 8 cases. Arch Neuropyschiatr 51: 475-486, 1993.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 115
EP 117
PG 3
ER
PT J
AU Lumniczky, K
Safrany, G
AF Lumniczky, Katalin
Safrany, Geza
TI Cancer Gene Therapy: Combination with Radiation Therapy and the Role of Bystander Cell Killing in the Anti-tumor Effect
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Lecture
DE gene therapy; bystander effect; gap junction
ID gene therapy; bystander effect; gap junction
AB Current anti-cancer modalities such as surgery, chemo- and radiation therapies have only limited success in cancer treatment. Gene therapy is a promising new tool to improve outcomes. In this review, first we summarize the various strategies to kill tumor cells, and then focus on the bystander effect of gene therapy. A variety of strategies, such as gene-directed enzyme pro-drug therapy, activation of an anti-tumor immune attack, application of replication-competent and oncolytic viral vectors, tumor-specific as well as radiation- and hypoxiainduced gene expression, might be applied to target tumor cells. We put special emphasis on the combination of these approaches with local tumor irradiation. Using the available vector systems, only a small portion of cancer cells contains the therapeutic genes under clinical situations. However, cells directly targeted by gene therapy will transfer death signals to neighboring cancer cells. This bystander cell killing improves the efficiency of cancer gene therapy. Death signals are delivered by cell-to-cell communication through gap junction intercellular contacts, release of toxic metabolites into the neighborhood or to larger distances, phagocytosis of apoptotic bodies, and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes that help the transfer of cytotoxic genes and/or metabolites into bystander cells. In conclusion, although bystander cell killing can improve therapeutic effects, there should be additional developments in cancer gene therapy for a more efficient clinical application.
C1 [Lumniczky, Katalin] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Anna u. 5., H-1221 Budapest, Hungary.
[Safrany, Geza] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Anna u. 5., H-1221 Budapest, Hungary.
RP Safrany, G (reprint author), Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, H-1221 Budapest, Hungary.
EM safrany@hp.osski.hu
CR Vile RG, Russell SJ, Lemoine NR: Cancer gene therapy: hard lessons and new courses. Gene Ther 7: 2-8, 2000
Inaba M, Sawaa H, Sadata A, Hamada H: Circumvention of 5- fluorouracil resistance in human stomach cancer cells by uracil phosphoribosyl transferase gene transduction. Jpn J Cancer Res 90: 349-354, 1999
Aghi M, Hochberg F, Breakfield XO: Prodrug activation enzymes in cancer gene therapy. J Gene Med 2: 148-164, 2000
Aghi M, Kramm CM, Chou T, et al: Synergistic anticancer effects of ganciclovir/thymidine kinase and 5-fluorocytosine/ cytosine deaminase gene therapies. J Natl Cancer Inst 90: 370- 380, 1998
Takamiya Y, Short MP, Ezzeddine ZD, et al: Gene therapy of malignant brain tumors: a rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells. J Neurosci Res 33: 493-503, 1992
Kanai F, Kawakami T, Hamada H, et al: Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene sensitizes cancer cells to low concentrations of 5- fluorouracil. Cancer Res 58: 1946-1951, 1998
Maron A, Gustin T, Le Roux A, et al: Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene: long-term follow-up by magnetic resonance imaging. Gene Ther 3: 315-322, 1996
Desaknai S, Lumniczky K, Esik O, et al: Local tumor irradiation enhances the anti-tumor effect of a double-suicide gene therapy system in a murine glioma model. J Gene Med 5: 377-385, 2003
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Dranoff G, Jaffee E, Lazenby A, et al: Vaccination with irradiated tumor cells engineered to secrete murine granulocytemacrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90: 3539-3543, 1993
Allione A, Consalvo M, Nanni P, et al: Immunizing and curative potential of replicating and non-replicating murine mammary adenocarcinoma cells engineered with interleukin IL-2, IL-4, IL-6, IL- 7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants. Cancer Res 54: 6022-6026, 1994
Li J, Andres ML, Fodor I, et al: Evaluation of pGL1-TNF-alpha therapy in combination with radiation. Oncol Res 10: 379-387, 1998
Staba MJ, Mauceri HJ, Kufe DW, et al: Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a human malignant glioma xenograft. Gene Ther 5: 293-300, 1998
Lumniczky K, Desaknai S, Mangel L, et al: Local tumor irradiation augments the anti-tumor effect of cytokine producing autologous cancer cell vaccines in a murine glioma model. Cancer Gene Ther 9: 44-52, 2002
Hann B, Balmain A: Replication of an E1B 55-kilodalton proteindeficient adenovirus ONYX-015 is restored by gain-of-function rather than loss-function p53 mutants. J Virol 77: 11588-11595, 2003
Nemunaitis J, Khuri F, Ganly I, et al: Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 19: 289-298, 2001
Nemunaitis J, Cunningham C, Buchanan A, et al: Intravenous infusion of a replication-selective adenovirus ONYX-015 in cancer patients: safety, feasibility and biological activity. Gene Ther 8: 746-759, 2001
Rogulski KR, Freytag SO, Zhang K, et al: In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy. Cancer Res 60: 1193-1196, 2000
Geoerger B, Grill J, Opolon P, et al: Potentiation of radiation therapy by the oncolytic adenovirus dl 1520 ONYX-015 in human malignant glioma xenografts. Br J Cancer 89: 577-584, 2003
Lin E, Nemunaitis J: Oncolytic viral therapies. Cancer Gene Ther 11: 643-664, 2004
Stanziale SF, Petrowsky H, et al: Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase. Surgery 132: 353-359, 2002
Timiryasova TM, Gridley DS, Chen B, et al: Radiation enhances the anti-tumor effects of vaccinia-p53 gene therapy in glioma. Technol Cancer Res Treat 2: 223-235, 2003
Robson T, Hirst DG: Transcriptional targeting in cancer gene therapy. J Biomed Biotechnol 110-137, 2003
Hallahan DE, Mauceri HJ, Seung LP, et al: Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1: 786- 791, 1995
Weichselbaum RR, Hallahan DE, Beckett MA, et al: Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. Cancer Res 54: 4266-4269, 1994
Horsman MR, Bohm L, Margison GP, et al: Tumor radiosensitizers – current status of development of various approaches: report of an International Atomic Energy Agency meeting. Int J Radiat Oncol Biol Phys 64: 551-561, 2006
Chastel C, Jiricny J, Jaussi R: Activation of stress-responsive promoters by ionizing radiation for deployment in targeted gene therapy. DNA Repair 3: 201-215, 2004
Manome Y, Kunieda T, Wen PY, et al: Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iodo-deoxyuridine. Hum Gene Ther 9: 1409-1417, 1998
Weichselbaum RR, Kufe DW, Hellman S, et al: Radiation-induced tumor necrosis factor-a expression: clinical application of transcriptional and physical targeting of gene therapy. Lancet Oncol 3: 665-671, 2002
Joki T, Nakamura M, Ohno T: Activation of the radiosensitive EGR-1 promoter induces expression of the herpes simplex virus thymidine kinase gene and sensitivity of human glioma cells to ganciclovir. Hum Gene Ther 6: 1507-1513, 1995
Worthington J, Robson T, O’Keeffe M, Hirst DG: Tumor cell radiosensitization using constitutive CMV and radiation inducible WAF1 promoters to drive the iNOS gene: a novel suicide gene therapy. Gene Ther 9: 263-269, 2002
Worthington J, McCarthy HO, Barrett E, et al: Use of the radiation- inducible WAF1 promoter to drive iNOS gene therapy as a novel anti-cancer treatment. J Gene Med 6: 673-680, 2004
Marples B, Greco O, Joiner MC, Scott SD: Radiogenetic therapy: strategies to overcome tumor resistance. Curr Pharm Des 9: 2105- 2112, 2003
Shibata T, Giaccia AJ, Brown JM: Development of a hypoxiaresponsive vector for tumor-specific gene therapy. Gene Ther 7: 493-498, 2000
J Gene Med Clinical Trial Site.
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Immonen A, Vapalahti M, Tyynela K, et al: AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study. Mol Ther 10: 967-972, 2004
Palmer DH, Young LS, Mautner V: Cancer gene-therapy: clinical trials. Trends Biotechnol 24: 76-82, 2006
Laheru D, Jaffe EM: Immunotherapy for pancreatic cancer – science driving clinical progress. Nat Rev Cancer 5: 459-467, 2005
Pulkkanen KJ, Yla-Herttuala S: Gene therapy for malignant glioma: current clinical status. Mol Ther 12: 585-598, 2005
Lawler SE, Peruzzi PP, Chiocca EA: Genetic strategies for brain tumor therapy. Cancer Gene Ther 13: 225-233, 2006
Makower D, Rozenblit A, Kaufman H, et al: Phase II clinical trial of intralesional administration of the oncolytic adenovirus ONYX-015 in patients with hepatobiliary tumors with correlative p53 studies. Clin Cancer Res 9: 693-702, 2003
Chiocca EA, Abbed KM, Tatter S, et al: A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1Battenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther 10: 958-966, 2004
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Park SY, Seol JW, Lee YJ, et al: IFN-gamma enhances TRAILinduced apoptosis through IRF-1. Eur J Biochem 271: 4222- 4228, 2004
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2006
VL 12
IS 2
BP 118
EP 124
PG 7
ER
PT J
AU Nagy, K
Szekely-Szuts, K
Izeradjene, K
Douglas, L
Tillman, M
Barti-Juhasz, H
Dominici, M
Spano, C
Luca Cervo, G
Conte, P
Houghton, AJ
Mihalik, R
Kopper, L
Petak, I
AF Nagy, Katalin
Szekely-Szuts, Kinga
Izeradjene, Kamel
Douglas, Leslie
Tillman, Mike
Barti-Juhasz, Helga
Dominici, Massimo
Spano, Carlotta
Luca Cervo, Gian
Conte, Pierfranco
Houghton, A Janet
Mihalik, Rudolf
Kopper, Laszlo
Petak, Istvan
TI Proteasome Inhibitors Sensitize Colon Carcinoma Cells to TRAIL-Induced Apoptosis via Enhanced Release of Smac/DIABLO from the Mitochondria
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TRAIL; epoxomicin; MG132; bortezomib/PS-341; Smac/DIABLO; colon carcinoma
ID TRAIL; epoxomicin; MG132; bortezomib/PS-341; Smac/DIABLO; colon carcinoma
AB The synergistic interaction between proteasome inhibitors and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising approach to induce cell death in tumor cells. However, the molecular and biochemical mechanisms of this synergism have been proven to be cell type specific. We therefore focused our investigation on TRAIL-resistant colon carcinoma cells in this study. DNA fragmentation, mitochondrial membrane depolarization and increased caspase-3-like enzyme activity was exclusively induced only by combined treatment with proteasome inhibitors (epoxomicin, MG132, bortezomib/PS-341) and TRAIL. The expression level of anti-apoptotic proteins (XIAP, survivin, Bcl-2, Bcl-XL), regulated by NF-κB transcription factor, was not effected by any of these treatments. TRAIL alone induced only partial activation of caspase-3 (p20), while the combination of TRAIL and proteasome inhibition led to the full proteolytic activation of caspase-3 (p17). Only the combination treatment induced marked membrane depolarization and the release of cytochrome c, HtrA2/Omi and Smac/DIABLO. Apoptosis-inducing factor (AIF) was not released in any of these conditions. These results are consistent with a model where the full activation of caspase-3 by caspase-8 is dependent on the release of Smac/DIABLO in response to the combined treatment. This molecular mechanism, independent of the inhibition NF-κB activity, may provide rationale for the combination treatment of colon carcinomas with proteasome inhibitors and recombinant TRAIL or agonistic antibody of TRAIL receptors.
C1 [Nagy, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Szekely-Szuts, Kinga] St. Jude Children’s Research Hospital, Department of Hematology-Oncology, Division of Molecular TherapeuticsMemphis, TN, USA.
[Izeradjene, Kamel] St. Jude Children’s Research Hospital, Department of Hematology-Oncology, Division of Molecular TherapeuticsMemphis, TN, USA.
[Douglas, Leslie] St. Jude Children’s Research Hospital, Department of Hematology-Oncology, Division of Molecular TherapeuticsMemphis, TN, USA.
[Tillman, Mike] St. Jude Children’s Research Hospital, Department of Hematology-Oncology, Division of Molecular TherapeuticsMemphis, TN, USA.
[Barti-Juhasz, Helga] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Dominici, Massimo] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Spano, Carlotta] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Luca Cervo, Gian] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Conte, Pierfranco] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Houghton, A Janet] St. Jude Children’s Research Hospital, Department of Hematology-Oncology, Division of Molecular TherapeuticsMemphis, TN, USA.
[Mihalik, Rudolf] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular PathologyBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Petak, Istvan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Petak, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM petak@kkk.org.hu
CR Chaudan D, Hideshima T, Mitsiades C, et al: Proteasome inhibitor therapy in multiple myeloma. Mol Cancer Ther 4:686- 692, 2005
Kloetzel PM: The proteasome and MHC class I antigen processing. Biochim Biophys Acta 1695:225-233, 2004
Roos-Mattjus P, Sistonen L: The ubiquitin-proteasome pathway. Ann Med 36:285-295, 2004
Sun L, Chen ZJ: The novel functions of ubiquitination in signaling. Curr Opin Cell Biol 16:119-126, 2004
Mani A, Gelmann EP: The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol 23:4776-4789, 2005
Petak I, Vernes R, Szucs KS, et al: A caspase-8-independent component in TRAIL/Apo-2L-induced cell death in human rhabdomyosarcoma cells. Cell Death Differ 10:729-739, 2003
Petak I, Houghton JA: Shared pathways: death receptors and cytotoxic drugs in cancer therapy. Pathol Oncol Res 7:95-106, 2001
Petak I, Douglas L, Tillman DM, et al: Pediatric rhabdomyosarcoma cell lines are resistant to Fas-induced apoptosis and highly sensitive to TRAIL-induced apoptosis. Clin Cancer Res 6:4119-4127, 2000
Zhang L, Fang B: Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 12:228-237, 2005
Guseva NV, Taghiyev AF, Sturm MT, et al: Tumor necrosis factor- related apoptosis-inducing ligand-mediated activation of mitochondria-associated nuclear factor-kappaB in prostatic carcinoma cell lines. Mol Cancer Res 2:574-584, 2004
Aggarwal BB, Bhardwaj U, Takada Y: Regulation of TRAILinduced apoptosis by ectopic expression of antiapoptotic factors. Vitam Horm 67:453-483, 2004
Yang LQ, Fang DC, Wang RQ, Yang SM: Effect of NF-kappaB, survivin, Bcl-2 and caspase3 on apoptosis of gastric cancer cells induced by tumor necrosis factor related apoptosis inducing ligand. World J Gastroenterol 10:22-25, 2004
Bortul R, Tazzari PL, Cappellini A, et al: Constitutively active Akt1 protects HL60 leukemia cells from TRAIL-induced apoptosis through a mechanism involving NF-kappaB activation and cFLIP(L, up-regulation. Leukemia 17:379-89, 2003
Ehrhardt H, Fulda S, Schmid I, et al: TRAIL induced survival and proliferation in cancer cells resistant towards TRAILinduced apoptosis mediated by NF-kappaB. Oncogene 22:3842-3852, 2003
Franco AV, Zhang XD, Van Berkel E, et al: The role of NF-kappa B in TNF-related apoptosis-inducing ligand, TRAIL)-induced apoptosis of melanoma cells. J Immunol 166:5337-5345, 2001
Jeremias I, Kupatt C, Baumann B, et al: Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells. Blood 91:4624-4631, 1998
Johnson TR, Stone K, Nikrad M, et al: The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells. Oncogene 22:4953-4963, 2003
Zhu H, Guo W, Zhang L, et al: Proteasome inhibitors-mediated TRAIL resensitization and Bik accumulation. Cancer Biol Ther 4:781-786, 2005
Zhu H, Zhang L, Dong F, et al: Bik/NBK accumulation correlates with apoptosis-induction by bortezomib, PS-341, Velcade, and other proteasome inhibitors. Oncogene 24:4993- 4999, 2005
Nikrad M, Johnson T, Puthalalath H, et al: The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther 4:443-449, 2005
Schneider P: Production of recombinant TRAIL and TRAIL receptor: Fc chimeric proteins. Methods Enzymol 322:325-3245, 2000
Leverkus M, Sprick MR, Wachter T, et al: Proteasome inhibition results in TRAIL sensitization of primary keratinocytes by removing the resistance-mediating block of effector caspase maturation. Mol Cell Biol 23:777-790, 2003
Chauhan D, Li G, Podar K, et al: Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma, MM, cells. Blood 104:2458-2466, 2004
LaVallee TM, Zhan XH, Johnson MS, et al: 2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway. Cancer Res 63:468-475, 2003
Creagh EM, Murphy BM, Duriez PJ, et al: Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins. J Biol Chem 279:26906-26914, 2004
Du C, Fang M, Li Y, et al: Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33-42, 2000
Ni H, Ergin M, Huang Q, et al: Analysis of expression of nuclear factor kappa B, NF-kappa B, in multiple myeloma: downregulation of NF-kappa B induces apoptosis. Br J Haematol 115:279-286, 2001
Berenson JR, Ma HM, Vescio R: The role of nuclear factor-kappaB in the biology and treatment of multiple myeloma. Semin Oncol 28:626-633, 2001
Tillman DM, Izeradjene K, Szucs KS, et al: Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis- inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res 63:5118-5125, 2003
Ganten TM, Koschny R, Haas TL, et al: Proteasome inhibition sensitizes hepatocellular carcinoma cells, but not human hepatocytes, to TRAIL. Hepatology 42:588-597, 2005
Lashinger LM, Zhu K, Williams SA, et al: Bortezomib abolishes tumor necrosis factor-related apoptosis-inducing ligand resistance via a p21-dependent mechanism in human bladder and prostate cancer cells. Cancer Res 65:4902-4908, 2005
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 133
EP 142
PG 10
ER
PT J
AU Johannessen, LA
Torp, HS
AF Johannessen, Linn Anne
Torp, Helge Sverre
TI The Clinical Value of Ki-67/MIB-1 Labeling Index in Human Astrocytomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Brain-tumors; gliomas-immunohistochemistry; Ki-67; prognosis
ID Brain-tumors; gliomas-immunohistochemistry; Ki-67; prognosis
AB The current WHO classification of human astrocytomas has limitations in predicting prognosis and diagnosis, and there is a need for additional factors. Several studies have investigated the clinical value of proliferative activity in these tumors, especially the Ki-67/MIB-1 labeling index (LI). The aim of this study was to review the literature on this topic to get a survey of the current experience. All studies show increasing values of Ki-67/MIB-1 LI with increasing grade of malignancy. Most of them demonstrate that MIB-1 LI differentiates well between diffuse astrocytomas WHO grade II (AII) and anaplastic astrocytomas (AA) and between AII and glioblastomas (GM), but not between AA and GM. There is, however, considerable overlap of indices between the different malignancy groups. Further, in most studies positive correlations between MIB-1 LI and survival are found, though the proposed cut-off values vary substantially between the reports. The studies reviewed report MIB-1 LI as an important prognostic factor in human astrocytomas. Due to the great spread of values between the various tumor grades, however, MIB-1 LI cannot be used as a diagnostic factor alone but should be used in combination with established criteria of histological malignancy. It may be especially useful in cases where histology reveals a low-grade astrocytoma whereas other parameters indicate a more malignant neoplasm. Thus, it is our opinion that MIB-1 LI should be a part of the routine investigation in patients with astrocytic tumors. Until larger multicenter studies based on standardized immunohistopathological procedures have been completed, each laboratory has to establish its own practice.
C1 [Johannessen, Linn Anne] St. Olavs Hospital, Trondheim University Hospital, Department of Pathology and Medical Genetics, Department of Laboratory Medicine, Children’s and Women’s Health, N-7006 Trondheim, Norway.
[Torp, Helge Sverre] St. Olavs Hospital, Trondheim University Hospital, Department of Pathology and Medical Genetics, Department of Laboratory Medicine, Children’s and Women’s Health, N-7006 Trondheim, Norway.
RP Torp, HS (reprint author), St. Olavs Hospital, Trondheim University Hospital, Department of Pathology and Medical Genetics, Department of Laboratory Medicine, Children’s and Women’s Health, N-7006 Trondheim, Norway.
EM sverre.torp@ntnu.no
CR Di Nishizaki T, Harada K, et al: Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. J Exp Clin Canc Res 16:389-394, 1997
Enestrom S, Vavruch L, Franlund B, et al: Ki-67 antigen expression as a prognostic factor in primary and recurrent astrocytomas. Neurochir 44:25-30, 1998
Gerdes J, Schwab U, Lemke H, et al: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13-20, 1983
Gerdes J, Li L, Schlueter, et al: Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki- 67. Am J Pathol 138: 867-873, 1991
Hilton DA, Love S, Barber R, et al: Accumulation of p53 and Ki-67 expression do not predict survival in patients with fibrillary astrocytomas or the response of these tumors to radiotherapy. Neurosurgery 42:724-729, 1998
Hsu DW, Louis DN, Efird JT, et al: Use of MIB-1, Ki-67, immunoreactivity in differentiating grade II and grade III gliomas. J Neuropathol Exp Neurol 56:857-865, 1997
Karamitopoulou E, Perentes E, Diamantis I, et al: Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1 monoclonal antibody on archival material. Acta Neuropathol 87:47-54, 1994
Key G, Becker MHG, Baron B, et al: New Ki-67-equivalent murine monoclonal antibodies, MIB 1-3, generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 68: 629-636, 1993
Khalid H, Shibata S, Kishikawa M, et al: Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors. Cancer 80: 2133-2140, 1997
Kleihuses P, Cavanee WK: World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of the Nervous System. IARC Press, Lyon, 2000
McKeever PE, Ross DA, Strawderman MS, et al: A comparison of the predictive power for survival in gliomas provided by MIB-1, bromodeoxyuridine and proliferating cell nuclear antigen with histopathologic and clinical parameters. J Neuropathol Exp Neurol 56:798-805, 1997
McKeever PE, Strawderman MS, Yamini B, et al: MIB-1 proliferation index predicts survival among patients with grade II astrocytoma. J Neuropathol Exp Neurol 57:931-936, 1998
Neder L, Colli BO, Machado HR, et al: MIB-1 labeling index in astrocytic tumors – a clinicopathologic study. Clin Neuropathol 6: 262-270, 2004
Ralte AM, Sharma MC, Karak AK, et al: Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors. Pathol Oncol Res 7:267-278, 2001
Reavey-Cantwell JF, Haroun RI, Zahurak M, et al: The prognostic value of tumor markers in patients with glioblastoma multiforme: analysis of 32 patients and review of the literature. J Neuro-Oncol 55:195-204, 2001
Sallinen PK, Haapasalo HK, Visakorpi T, et al: Prognostication of astrocytoma patient survival by Ki-67, MIB-1), PCNA, and S-phase fraction using archival paraffin-embedded samples. J Pathol 174: 275-282, 1994
Schiffer D, Cavalla P, Chio A, et al: Proliferative activity and prognosis of low-grade astrocytomas. J Neuro-Oncol 34:31-35, 1997
Torp SH: Diagnostic and prognostic role of Ki67 immunostaining in human astrocytomas using four different antibodies. Clin Neouropathol 21:252-257, 2002
Torp SH, Alsaker M: Ki-67 immunoreactivity, basic fibroblast growth factor, bFGF, expression, and microvessel density as supplementary prognostic tools in low-grade astrocytomas. Pathol Res Pract 198:261-265, 2002
Wakimoto H, Aoyagi M, Nakayama T, et al: Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas. Cancer 77:373-380, 1996
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 143
EP 147
PG 5
ER
PT J
AU Lorincz, T
Toth, J
Badalian, G
Timar, J
Szendroi, M
AF Lorincz, Tamas
Toth, Jozsef
Badalian, Gayane
Timar, Jozsef
Szendroi, Miklos
TI HER-2/neu Genotype of Breast Cancer May Change in Bone Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; bone metastatic; HER-2
ID breast cancer; bone metastatic; HER-2
AB The genotype of breast cancer (BRC) is considered to be relatively stable during tumor progression, accordingly, determination of the estrogen receptor and HER-2/neu status is currently based on the primary tumor. However, recent data suggest that the gene expression profile of the metastatic lesion can be different compared to that of the primary BRC. Accordingly, it is possible that the HER-2/neu status is different in the metastatic lesion and the primary BRC. Since the bone is the most frequent metastatic site during the progression of BRC, we have analyzed the HER-2/neu status of 48 bone metastatic BRC cases by immunohistochemistry and fluorescent in situ hybridization, and it was possible to compare it to the primary site in 23 cases. The frequency of HER-2/neu amplification of BRC in the primary tumors was found to be 17.4% compared to 10.5% in bone metastases. Half of BRC cases with HER-2/neu amplification lost this genotype in bone metastases (4/23 versus 2/23, respectively) and even in the 2 cases where HER-2/neu amplification was retained in the metastases, the copy number was found to be decreased compared to the primary tumor. Based on our data and previous reports in the literature, we suggest to perform HER-2/neu testing both on primary tumor and samples obtained from BRC metastases, at least in case of primary tumors with HER-2/neu amplification, before introduction of HER-2/neu-targeting therapy.
C1 [Lorincz, Tamas] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Toth, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Badalian, Gayane] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Mendelsohn J, Baselga J: The EGF receptor family as targets for cancer therapy. Oncogene 19: 6550-6565, 2000
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Yu D, Hung MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 19: 6115-6121, 2000
Tsuda H, Hirohashi S, Shimotaso Y, et al: Correlation between long term survival in breast cancer patients and amplification of two putative oncogene co-amplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res 49:3104-3108, 1989
de Bono JS, Rowinsky EK: The ErbB receptor family: a therapeutic target for cancer. Trends Mol Med 8, 4 suppl): S19-S26, 2002
Ross JS, Fletcher JA: HER-2/neu, c-erb-B2, gene and protein in breast cancer. Am J Clin Pathol 112: 53-67, 1999
Cobleigh MA, Vogel CL, Triphaty D et al: Multinational study of the efficacy and safety of humanized anti-HER-2/NEU monoclonal antibody in woman who have HER-2/NEU-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17: 2639-2648, 1999
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Kunitomo K, Inoue S, Ichihara F et al: A case of metastatic breast cancer with outgrowth of HER-2/NEU-negative cells after eradication of HER-2/NEU-positive cells by humanized anti-HER-2/NEU monoclonal antibody, trastuzumab, combined with docetaxel. Hum Pathol 35: 379-381, 2004
Zidan J, Dashkovsky I, Stayerman C et al: Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93: 552-556, 2005
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Press MF, Slamon DJ, Flom KJ et al: Evaluation of HER-2/neu gene amplification and overexpression: comparison of frequently used assay methods in a molecularly characterized cohort of breast cancer specimens. J Clin Oncol 20: 3095-3105, 2002
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Woelfle U, Cloos J et al: Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res 63:5679-5684, 2003
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Gong Y, Booser DJ, Sneige N: Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer 103: 1763-1769, 2005
Regitnig P, Schippinger W, Lindbauer M et al. Change of HER-2/neu status in a subset of distant metastases from breast carcinomas. J Pathol 203: 918-926, 2004
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 149
EP 152
PG 4
ER
PT J
AU Nogueira, CM
Guedes Neto, dPE
Rosa, WM
Zettler, E
Zettler, GC
AF Nogueira, Cordoni Mauricio
Guedes Neto, de Paula Ernesto
Rosa, Wengrover Marcos
Zettler, Eduardo
Zettler, Galleano Claudio
TI Immunohistochemical Expression of p16 and p53 in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma of the Vulva
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE vulvar cancer; vulvar intraepithelial neoplasia; p16; p53
ID vulvar cancer; vulvar intraepithelial neoplasia; p16; p53
AB This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva. We also analyzed the relationship between p16 and p53 immunoexpression in women younger vs. older than 55 years of age. Seventyseven histologic samples of vulvar tissue, treated surgically between June 2000 and November 2004 at the Complexo Hospitalar Santa Casa (Porto Alegre, Brazil), were investigated. We analyzed 28 cases of VIN, 37 cases of SCC and 12 normal vulvar tissues. The percentage of immunohistochemical positivity for p16 had the following distribution across the groups: VIN: 21.4% (6/28), cancer: 24.3% (9/37) and control: absent (p=0.202). p53 expression showed the following percentages: VIN: 60.7% (17/28), cancer: 18.9% (7/37) and control: 8.3% (1/12) (p=0.01). p16 expression in the cancer group (mean age: 63.4 years) was positive in 6 and 3 cases of women younger or older than 55 years, respectively (54.5% vs. 11.5%, p=0.01). p53 expression was not detected in young females with cancer, while it was expressed in 7/26 (26.9%) cases of the group of females older than 55 years of age (p=0.08). Our results suggest an increase in the immunohistochemical expression of p16 protein in young women with squamous cell carcinoma of the vulva, and a possible association with a low expression of p53.
C1 [Nogueira, Cordoni Mauricio] Complexo Hospitalar Santa Casa de Porto Alegre, Santa Rita Cancer Center, Gynecologic Oncology Group, Rua Prof. Annes Dias, 285, 90020-090 Porto Alegre, Brazil.
[Guedes Neto, de Paula Ernesto] Complexo Hospitalar Santa Casa de Porto Alegre, Santa Rita Cancer Center, Gynecologic Oncology Group, Rua Prof. Annes Dias, 285, 90020-090 Porto Alegre, Brazil.
[Rosa, Wengrover Marcos] Complexo Hospitalar Santa Casa de Porto Alegre, Santa Rita Cancer Center, Gynecologic Oncology Group, Rua Prof. Annes Dias, 285, 90020-090 Porto Alegre, Brazil.
[Zettler, Eduardo] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, Brazil.
[Zettler, Galleano Claudio] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, Brazil.
RP Nogueira, CM (reprint author), Complexo Hospitalar Santa Casa de Porto Alegre, Santa Rita Cancer Center, Gynecologic Oncology Group, 90020-090 Porto Alegre, Brazil.
EM nogueira@santacasa.tche.br
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Fregonesi PA, Teresa DB, Duarte RA, et al: p16(INK4A, immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J Histochem Cytochem 51: 1291-1297, 2003.
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Hollstein M, Sidransky D, Vogelstein B, Harris C: p53 mutations in human cancers. Science 117: 291-294, 1991.
Ellis PE, Fong LF, Rolfe KJ, et al: The role of p53 and Ki67 in Paget’s disease of the vulva and the breast. Gynecol Oncol 86: 150-156, 2002.
Val IC, Almeida GF, Valiante PM, et al: Vulvar intraepithelial neoplasia p53 expression in recurrent/progressive cases. J Reprod Med 49: 868-874, 2004.
Branton PA: College of American Pathologists, CAP). Protocol Revision date: January 2005., Based on WHO, AJCC/UICC, TNM 6th and FIGO Annual Report). Washington, DC);, Protocol applies to pre-malignant and invasive carcinomas of the vulva), 2005.
Santos M, Montagut C, Mellado B, et al: Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva. Int J Gynecol Pathol 23: 206- 214, 2004.
Seters M, Beurden M, Craen AJ: Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol 97: 645-651, 2005.
Kaufman RH: Intraepithelial neoplasia of the vulva. Gynecol Oncol 56:8-21, 1995.
Riethdorf S, Neffen E, Cviko A, et al: P16(INK4A, as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol 35: 1477- 1483, 2004.
Esrig D, Spruck CH, Nichols PW: p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade and stage in bladder cancer. Am J Pathol 143: 1389-1392, 1993.
Pilotti S, Donghi R, Giarola M, et al: Papilloma virus, p53 alteration and primary carcinoma of the vulva. Eur J Cancer 29: 924-925, 1993.
Chen TM, Chen CA, Hsieh CY, et al: The state of p53 in primary human cervical carcinomas and its effects in human papillomavirus- immortalized human cervical cells. Oncogene 8: 1511-1518, 1993.
Koyamatsu Y, Yokoyama M, Nakao Y, et al: A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical, vaginal, and vulvar carcinomas. Gynecol Oncol 90: 547-551, 2003.
Gualco M, Bonin S, Foglia G: Morphologic and biologic studies on ten cases of verrucous carcinoma of the vulva supporting the theory of a discrete clinicopathologic entity. Int J Gynecol Cancer 13: 317-324, 2003.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 153
EP 157
PG 5
ER
PT J
AU Szegedi, I
Kiss, Cs
Karaszi,
Vamosi, Gy
Szollosi, J
Kovacs, P
Benko, I
AF Szegedi, Istvan
Kiss, Csongor
Karaszi, Eva
Vamosi, Gyorgy
Szollosi, Janos
Kovacs, Peter
Benko, Ilona
TI Differential Regulation of Umbilical Cord Blood and Leukemic B Cells by Interferon-Alpha (IFN-α): Observations in Cultured Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; B cells; colony formation; interferon-alpha; type II Fcy receptor
ID apoptosis; B cells; colony formation; interferon-alpha; type II Fcy receptor
AB The exact mechanism of the beneficial therapeutic action of interferon-a (IFN-α) in B-cell-lineage malignancies has not been adequately explained. Here we report on the differential effect of IFN-α2b on non-malignant B cells of umbilical cord blood and leukemic B-cell lines JY, BL-41 and BCBL-1. Leukemic cell proliferation was characterized by colony assay, whereas apoptosis was investigated by flow cytometry of propidium iodide-stained cells. The degree of differentiation was evaluated by measuring the expression level of Fcγ receptor-II (FcγRII) labeled with anti-CD32-FITC monoclonal antibody using flow cytometry. IFN-α protected umbilical cord blood CD19-positive B lymphocytes from apoptotic cell death in vitro. IFN-α significantly decreased colony formation of all three cell lines, and in contrast to normal cells, induced apoptosis in JY and BL-41 and excessive necrosis in HHV-8 infected BCBL-1 cells. FcγRII was upregulated both in normal and in leukemic B cells as indicated by an increase both in the proportion of CD32-positive cells and the mean fluorescence intensity. From our results it seems that antiproliferative, apoptotic and differentiative effects of IFN-α are interrelated but distinct cellular events, which are differentially regulated in normal, leukemic and virus-infected cells of the B-cell lineage.
C1 [Szegedi, Istvan] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4012 Debrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4012 Debrecen, Hungary.
[Karaszi, Eva] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Vamosi, Gyorgy] University Medical School of Debrecen, Department of Biophysics and Cell BiologyDebrecen, Hungary.
[Szollosi, Janos] University Medical School of Debrecen, Department of Biophysics and Cell BiologyDebrecen, Hungary.
[Kovacs, Peter] University of Debrecen, Department of Pharmacology and PharmacotherapyDebrecen, Hungary.
[Benko, Ilona] University of Debrecen, Department of Pharmacology and PharmacotherapyDebrecen, Hungary.
RP Kiss, Cs (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4012 Debrecen, Hungary.
EM kisscs@dote.hu
CR Balmelli C, Vincent IE, Rau H et al: Fc gamma RII-dependent sensitisation of natural interferon-producing cells for viral infection and interferon-alpha responses. Eur J Immunol 35: 2406-2415, 2005
Benko I, Kovacs P, Szegedi I, et al: Effect of myelotropic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia. N-S Arch Pharmacol 363: 499-508, 2001
D’Agostino G, Arico E, Santodonato L et al: Type I consensus IFN, IFN-con1, gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in SCID mice. J Interferon Cytokine Res 19: 1305-1316, 1999
Heslop HE, Hoffbrand AV: Interferons in haematological malignancy. Recent Adv Haemat 7: 131-148, 1992
Jewell AP: Interferon-alpha, bcl-2 expression and apoptosis in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 21: 43- 47, 1996
Kiss C: Interferons in pediatric oncology: end of the beginning or beginning of the end? Med Pediatr Oncol 30: 364-366, 1998
Kiss C, Surrey S, Schreiber AD et al: Human c-kit ligand, stem cell factor, induces platelet Fc receptor expression in megakaryocytic cells. Exp Hematol 24: 1232-1237, 1996
Martinez-Lostao L, Briones J, Forne I et al: Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 46: 435-442, 2005
McSweeney EN, Giles FJ, Worman CP et al: Recombinant alpha 2a interferon therapy in the treatment of patients with early stage B chronic lymphatic leukaemia. Br J Haemat 85: 77-83, 1993
Mikala G, Xie J, Berencsi G, Kiss C et al: Human herpesvirus 8 in hematologic diseases. Pathol Oncol Res 5: 73-79, 1999
Miyauchi J, Kelleher CA, Yang YC et al: The effects of three recombinant growth factors, IL-3, GM-CSF, and G-CSF on the blast cells of acute myeloblastic leukemia maintained in shortterm suspension culture. Blood 70: 657-663, 1987
Pearse RN, Feinman R, Shuai K et al: Interferon g-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that induces the 91-kDa subunit of transcription factor ISGF3. Proc Natl Acad Sci USA 90: 4314- 4318, 1993
Picchio GR, Sabbe RE, Gulizia RJ et al: The KSHV/HHV8- infected BCBL-1 lymphoma line causes tumors in SCID mice but fails to transmit virus to a human peripheral blood mononuclear cell graft. Virology 238: 22-29, 1997
Pouge SL, Preston BT, Stalder J et al: The receptor for type I IFNs is highly expressed on peripheral blood B cells and monocytes and mediates a distinct profile of differentiation and activation of these cells. J Interferon Cytokine Res 24: 131-139, 2004
Pozharskaya VP, Weakland LL, Offermann MK: Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells. J Gen Virol 85: 2779- 2787, 2004
Renne R, Zhong W, Herndier B et al: Lytic growth of Kaposi’s sarcoma-associated herpesvirus, Human herpesvirus 8, in culture. Nat Med 2: 342-346, 1996
Santavenere E, Di Pietro R, Centurione MA et al: Synergistic regulatory effects of TNF alpha, IL-1 alpha and IFN alpha on the growth and differentiation of Daudi lymphoma cells. Cell Biol Int 20: 335-338, 1996
Sarmay G, Koncz G, Gergely J: Human type II Fcγ receptors inhibit B cell activation by interacting with the p21ras-dependent pathway. J Biol Chem 271: 30499-30504, 1996
Szollosi J, Horejsi V, Bene L et al: Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules, CD53, CD81, and CD82, at the surface of a B cell line JY. J Immunol 157: 2939-2946, 1996
Zimring JC, Goodburn S, Offerman MK: Human herpesvirus encodes an interferon regulatory factor, IRF, homolog that represses IRF-1 mediated transcription. J Virol 72: 701-707, 1998
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 159
EP 163
PG 5
ER
PT J
AU Malik, A
Deb, P
Sharma, ChM
Sarkar, Ch
AF Malik, Ajay
Deb, Prabal
Sharma, Chand Mehar
Sarkar, Chitra
TI Neuropathological Spectrum of Pilocytic Astrocytoma - an Indian Series of 120 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pilocytic astrocytoma; vascular spectrum; angiomatous proliferation; glomeruloid vessels; perivascular; hyalinization; hemosiderin
ID Pilocytic astrocytoma; vascular spectrum; angiomatous proliferation; glomeruloid vessels; perivascular; hyalinization; hemosiderin
AB Pilocytic astrocytomas (PAs) are generally well circumscribed, slowly growing, cystic tumors, occurring in the pediatric age group. Our aims were to retrospectively analyze the neuropathological spectrum of PA, and correlate it with various clinicopathological features. A total of 120 PAs, diagnosed and managed at this center during a 5-year period, were included. The study population had a mean age of 18.9 years, with male predominance (68.3%), and demonstrated predilection for posterior fossa (61.7%). On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers (66.7%) and eosinophilic granular bodies (60%) were present in the majority of cases. Vascular features were characterized by perivascular hyalinization (51.7%), angiomatous proliferation (21.7%) and glomeruloid changes (21.7%). Hemosiderin-laden macrophages were noted in 37.1% of cases. Further, 60.8% showed lymphoplasmacytic infiltration, while atypia and necrosis were present in 25.8% and 1.7% of cases, respectively. Statistical evaluation revealed significant correlation of angiomatous proliferation with age (≤12 and >12-year age groups) (p=0.011); and of hemosiderin deposition with angiomatous proliferation (p=0.006), perivascular hyalinization (p=0.035), and age (≤12 and >12-year age groups) (p=0.028). This study emphasizes that though PAs generally display classical histomorphology, diagnosis may be challenging in patients with unusual clinicopathological features, e.g. in older patients, uncommon location, absence of biphasic pattern, or presence of nuclear atypia, mitotic figures and necrosis, and also in cases of small biopsies. In the absence of diagnostic histology enumerated above, vascular features like angiomatous proliferation, glomeruloid changes and perivascular hyalinization, along with hemosiderinladen macrophages and perivascular lymphocytic infiltration should be considered as surrogate histological markers of PA.
C1 [Malik, Ajay] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029, New Delhi, India.
[Deb, Prabal] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029, New Delhi, India.
[Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029, New Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029, New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029, New Delhi, India.
EM drchitrasarkar@yahoo.com
CR Badhe PB, Chauhan PP, Mehta NK: Brainstem gliomas – a clinicopathological study of 45 cases with p53 immunohistochemistry. Indian Cancer 41: 170-174, 2004
Bell D, Chitnavis BP, Al-Sarraj S, et al: Pilocytic astrocytoma of the adult—clinical features, radiological features and management. Br J Neurosurg 18: 613-616, 2004
Berroir S, Lafitte F, Heran F, et al: Pilocytic astrocytoma: unusual feature. J Neuroradiol 28:249-252, 2001
Beutler AS, Hsiang JK, Moorhouse DF, et al: Pilocytic astrocytoma presenting as an extra-axial tumor in the cerebellopontine angle: case report. Neurosurgery 37:125-128, 1995
Boch AL, Cacciola F, Mokhtari K, et al: Benign recurrence of a cerebellar pilocytic astrocytoma 45 years after gross total resection. Acta Neurochirurgica, Wien, 142:341-346, 2000
Burger PC, Scheithauer BW, Paulus W, et al: Pilocytic astrocytoma. In: Pathology and Genetics of Tumors of the Nervous System., Eds: Kleihues P and Cavenee WK), IARC Press, Lyon, France, 2000, pp. 45-47
Burger PC, Scheithauer BW, Vogel FS: The brain tumors. In: Surgical Pathology of the Nervous System and its Coverings., Eds: Burger PC, Scheithauer BW, Vogel FS), Churchill Livingstone, New York, 2002, pp.160-378
Burkhard C, Di Patre PL, Schuler D, et al: A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma. J Neurosurg 98: 1170-1174, 2003
Coakley KJ, Huston J, Scheithauer BW, et al: Pilocytic astrocytomas: well-demarcated magnetic resonance appearance despite frequent infiltration histology. Mayo Clinics Proceedings 70: 747-751, 1995
Darwish B, Koleda C, Lau H, et al: Juvenile pilocytic astrocytoma ‘pilomyxoid variant’ with spinal metastases. J Clin Neurosci 11: 640-642, 2004
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Forsyth PA, Shaw EG, Scheithauer BW, et al: Supratentorial pilocytic astrocytomas. A clinicopathologic, prognostic, and flow cytometric study of 51 patients. Cancer 72:1335-1342, 1993
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Hadjipanayis CG, Kondziolka JC, Flickinger JC, Lunsford LD: The role of stereotactic radiosurgery for low-grade astrocytomas. Neurosurgery Focus 14: e15, 2003
Ideguchi M, Nishizaki T, Harada K, et al: Pilocytic astrocytoma of the velum interpositum. Neurol Med Chir, Tokyo, 38:283- 286, 1998
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Kan P, Gottfried O, Blumenthal DT, et al: Oligodendroglioma and juvenile pilocytic astrocytoma presenting as synchronous primary brain tumors. Case report with histological and molecular differentiation of the tumors and review of the literature. J Neurosurg 100:700-705, 2004
Katsetos CD, Krishna L: Lobar pilocytic astrocytomas of the cerebral hemispheres: I. Diagnosis and nosology. Clin Neuropathol 13:295-305, 1994
Kleihues P, Cavenee WK. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of the Nervous System. IARC Press, Lyon, France, 2000.
Komotar RJ, Burger PC, Carson BS et al: Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54:72-79, 2004
Komotar RJ, Carson BS, Rao C, et al: Pilomyxoid astrocytoma of the spinal cord: report of three cases. Neurosurgery 56:191, 2005
Komotar RJ, Mocco J, Jones JE, et al: Pilomyxoid astrocytoma: diagnosis, prognosis, and management. Neurosurgery Focus 18:e7, 2005
Lee YY, Van Tassel P, Bruner JM, et al: Juvenile pilocytic astrocytomas: CT and MR characteristics. Am J Roentgenol. 152:1263-1270, 1989
Lesniak MS, Klem JM, Weingart J, Carson BS Sr: Surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas. Pediatr Neurosurg 39:314-322, 2003
Lones MA, Verity MA: Fatal hemorrhage in a cerebral pilocytic astrocytoma-adult type. Acta Neuropathol, Berlin, 81:688-690, 1991
Machen SK, Prayson RA: Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Hum Pathol 29:1511-1516, 1998
Maruyama K, Morita A, Shibahara J, et al: Multifocal pilocytic astrocytomas with ependymal differentiation in the bilateral medial temporal lobes: case report. Neurol Med Chir, Tokyo, 45:411-414, 2005
Ohgaki H, Kleihues P: Epidemiology and etiology of gliomas. Acta Neuropathol, Berl). 109: 93-108, 2005
Philipson MR, Timothy J, Chakrobarthy A, Towns G: Pilocytic astrocytoma of a spinal nerve root. Case report. Neurosurg 97:110-112, 2002
Rickert CH, Paulus W: Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst. 17:503-511, 2001
Rosemberg S, Fujiwara D: Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution. Childs Nervous System 21:940-944, 2005
Tomlinson FH, Scheithauer BW, Hayostek CJ, et al: The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study. J Clin Neurol 9: 301-310, 1994
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 164
EP 171
PG 8
ER
PT J
AU Helal, EATh
Fadel, TM
El-Sayed, KN
AF Helal, El A Thanaa
Fadel, T Mona
El-Sayed, K Naglaa
TI Human Papilloma Virus and p53 Expression in Bladder Cancer in Egypt: Relationship to Schistosomiasis and Clinicopathologic Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Egyptian patients; bladder carcinoma; schistosomiasis; p53; HPV
ID Egyptian patients; bladder carcinoma; schistosomiasis; p53; HPV
AB The aim of the current study was to compare the role of p53 and human papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated carcinoma of the urinary bladder. To achieve this aim, we investigated 114 bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for human papillomavirus by in situ hybridization technique. The results revealed that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas. In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein expression was significantly higher in poorly differentiated tumors. However, it was significantly higher in locally more invasive tumors in the schistosomal carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in situ. These results suggest that p53 immunohistochemistry can be a prognostic factor in both schistosomal and nonschistosomal bladder cancer. More importantly, HPV does not seem to play a role in the pathogenesis of either type of bladder cancer in our country.
C1 [Helal, El A Thanaa] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
[Fadel, T Mona] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
[El-Sayed, K Naglaa] Faculty of Science, Cairo University, Department of ZoologyCairo, Egypt.
RP Helal, EATh (reprint author), Ain Shams Faculty of Medicine, Department of Pathology, Cairo, Egypt.
EM thanaahelal@hotmail.com
CR Khaled HM: Bladder cancer and bilharziasis today. Cancer J 6: 65-71, 1993.
El-Bolkainy MN, Ghoneim MA, Mansour MA: Carcinoma of the bilharzial bladder in Egypt. Clinical and pathological features. Br J Urol 44: 561-570, 1972.
El-Sebai I: Cancer of the bilharzial bladder. Urol Res 6: 233- 236, 1978.
El-Merzabani MM, El-Aaser AA, Zakhary NI: A study on the etiological factors of bilharzial bladder cancer in Egypt. 1. Nitrosoamines and their precursors in urine. Eur J Cancer 15: 287-291, 1979.
El-Bolkainy MN, Mokhtar NM, Ghoneim MA, Hussein MH: The impact of schistosomiasis on the pathology of bladder carcinoma. Cancer 48: 2643-2648, 1981.
Mostafa MH, Sheweita SA, O’Connor PJ: Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 12: 97-111, 1999.
Wright C, Mellon K, Johnston P, et al. Expression of mutant p53, c-erb B2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer 63: 967-970, 1991.
Soini Y, Turpeenniemi-Hujamen T, Kamel D, et al: p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression. Br J Cancer 68: 1029–1035, 1993.
Harney J, Murphy DM, Jones M, Mothersill C: Expression of p53 in urothelial cell cultures from tumor-bearing and tumorfree patients. Br J Cancer 71: 25-29, 1995.
Glick SH, Howell LP, White RW: Relationship of p53 and bcl2 to prognosis in muscle-invasive transitional cell carcinoma of the bladder. J Urol 155: 1754-1757, 1996.
Hermann GG, Horn T, Steven K: The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer. J Urol 159: 91-94, 1998.
Niehans GA, Kratzke RA, Froberg-MK, et al: G1 check point protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder. Br J Cancer 80: 1175-1184, 1999.
Steiner G, Bierhoff E, Schmidt D, et al: p53 immunoreactivity in biopsy specimens of T1 G3 transitional cell carcinoma of the bladder, a helpful parameter in guiding the decision for or against cystectomy? Eur J Cancer 36: 610-614, 2000.
Habuchi T, Takahashi R, Yamada H, et al: Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer. Cancer Res 53: 3795-3799, 1993.
Kamel D, Soini Y, Nuorva K, et al: p53 and c-erb2 expression in schistosomal urinary bladder carcinomas and schistosomal cystitis with premalignant lesions. Virchows Arch 424: 349-355, 1994.
Warren W, Biggs PJ, el Baz M, et al: Mutations in the p53 gene in schistosomal bladder cancer: a study of 92 tumors from Egyptian patients and a comparison between mutational spectra from schistosomal and non-schistosomal urothelial tumors. Carcinogenesis 16: 1181-1189, 1995.
Ramchurren N, Cooper K, Summerhay IC: Molecular events underlying schistosomiasis-related bladder cancer. Int J Cancer 62: 237-244, 1995.
Chaudhary KS, Abel PD, Khandan-Nia N, et al: Expression of bcl-2 and p53 oncoproteins in schistosomiasis-associated transitional and squamous cell carcinoma of the urinary bladder. Br J Urol 79: 78-84, 1997.
Bryant P, Skelly J, Wilson D: Demonstration of papillomavirus structural antigen in human urinary bladder neoplasia. Br J Urol 60: 405-409, 1987.
Kitamura T, Yogo Y, Ueki T, et al: Presence of human papillomavirus type 16 genome in bladder carcinoma in situ of a patient with mild immunodeficiency. Cancer Res 48: 7207-7211, 1988.
Bryant P, Davies P, Wilson D. Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridization. Br J Urol 68: 49-52, 1991.
Anwar K, Naiki H, Nakakuki K, Inuzuka M: High frequency of human papillomavirus infection in carcinoma of the urinary bladder. Cancer 70: 1967-1973, 1992.
Chetsange C, Malnstrom PU, Gyllensten U, et al: Low incidence of human papillomavirus type 16 DNA in bladder tumor detected by the polymerase chain reaction. Cancer 69: 1208-1211, 1992.
Lopez-Beltron A, Munoz E: Transitional cell carcinoma of the bladder: low incidence of human papillomavirus DNA detected by the polymerase chain reaction and in situ hybridization. Histopathology 26: 565-569, 1995.
Tenti P, Zappatore R, Roagnoli S, et al: p53 overexpression and human papillomavirus infection in transitional cell carcinoma of the urinary bladder: correlation with histological parameters. J Pathol 178: 65-70, 1996.
Cooper K, Haffajee Z, Taylor L: Human papillomavirus and schistosomiasis associated bladder cancer. Mol Pathol 50: 145- 148, 1997.
Guidici C, Ferrario D, Forlni N, et al: Study of human papillomavirus via chemiluminescence technique and polymerase chain reaction in transitional cell carcinoma of the bladder. Pathologica 90: 776-782, 1998.
Aynaud O, Tranboloc P, Orth G: Lack of evidence for a role of human papillomavirus in transitional cell carcinoma of the bladder. J Urol 159: 86-89, 1998.
Simoneau M, La Rue H, Fradet Y. Low frequency of human papillomavirus in initial papillary bladder tumors. Urol Res 27: 180-184, 1999.
De-Goetani C, Ferrori G, Righi E, et al: Detection of human papillomavirus DNA in urinary bladder carcinoma by in situ hybridization. J Clin Pathol 52: 103-106, 1999.
Khaled HM, Raafat A, Mokhtar N, et al: Human papillomavirus infection and overexpression of p53 protein in bilharzial bladder cancer. Tumori 87: 256-261, 2001.
Mostofi FK, Sobin LH, Torloni H: Histologic typing of urinary bladder tumors. In: International Histological Classification of Tumors, Vol10). WHO, Geneva, 1973.
Mostofi FK, Davis CJ, Sestrhenn IA: Histologic typing of urinary bladder tumors. In: World Health Organization International Histological Classification of Tumors 2nd ed. Heidelberg, Germany: Springer Verlag, Berlin, 1999.
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Hsu SM, Raine L: Use of avidin-biotin-peroxidase complex, ABC, in immunoperoxidase technique. A comparison between ABC and unlabelled, PAP, procedures. J Hischochem Cytochem 29: 577-580, 1981.
Gabert HE, Muller W, Schneiders A, et al: The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma. Cancer 76: 720-726, 1995.
Krager B: Preparation and use of biotinylated oligonucleotide probes. Focus 11: 57-58, 1989.
Ross RK, Jones PA, Yu MC: Bladder cancer: Epidemiology and pathogenesis. Semin Oncol 23:536-545, 1996.
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Plastiras D, Moutzouris G, Barbatis C, et al: Can p53 nuclear over-expression, bcl2 accumulation and PCNA status be of prognostic significance in high risk superficial and invasive bladder tumors? Eur J Surg Oncol 25: 61-65, 1999.
Herr HW, Bajorin DF, Scher HI, et al: Can p53 help select patients with invasive bladder cancer for bladder preservation. J Urol 161: 20-22, 1999.
Llopis J, Alcaraz A, Ribal MJ, et al: p53 expression predicts progression and poor survival in T1 bladder tumors. Eur Urol 37: 644-653, 2000.
La Rue H, Simoneau M, Fradet Y. Human papillomavirus in transitional cell carcinoma of the urinary bladder. Clin Cancer Res 1: 435-440, 1995.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 173
EP 178
PG 6
ER
PT J
AU Elek, G
Lapis, K
AF Elek, Gabor
Lapis, Karoly
TI A Path or a New Road in Laboratory Diagnostics? Biological Mass Spectrometry: Facts and Perspectives
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE serum proteome; tissue proteome; mass spectrometry; matrix; protein biomarker; SELDI; ProteinChip system; proteomics; genomics
ID serum proteome; tissue proteome; mass spectrometry; matrix; protein biomarker; SELDI; ProteinChip system; proteomics; genomics
AB Proteins in tissues and biofluids and their many attributes define the proteome. Proteome can be directly correlated to known diseases and histological regions allowing the diagnosis and monitoring of disease progression as well predicting the patient’s response to specific treatments. Proteomics performs large-scale, high-throughput characterization of the human proteome, among others by biological mass spectrometry. Proteinchip technology coupled with bioinformatics is able to screen any protein source for putative disease biomarkers from a small sample volume (microliter range) by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). This article discusses on a basic level both the technology and reliability of these methods.
C1 [Elek, Gabor] Semmelweis University, Kutvolgyi Clinical CentreBudapest, Hungary.
[Lapis, Karoly] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
RP Lapis, K (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM klapis@korb1.sote.hu
CR Anderson NG, Matheson A, Anderson NL: Back to the future: the human protein index, HPI, and the agenda for post-proteomic biology. Proteomics 1:3-12, 2001.
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Bonner RF, Emmert-Buck M, Cole K, et al: Laser capture microdissection: molecular analysis of tissue. Science 278:1481-1483, 1997.
Caprioli RM, Farmer TB, Gile J: Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751-4760, 1997.
Chaurand P, Schwartz SA, Reyzer ML, et al: Imaging mass spectrometry: principles and potentials. Toxicol Pathol 33:92- 101, 2005.
Chaurand P, Sanders ME, Jensen RA, et al: Proteomics in diagnostic pathology. Profiling and imaging proteins directly in tissue sections. Am J Pathol 165:1057-1068, 2004.
Chaurand P, Schwartz SA, Bilheimer D, et al: Integrating histology and imaging mass spectroscopy. Anal Chem 76:1145- 1155, 2004.
Chaurand P, Schwartz SA, Caprioli RM: Profiling and imaging proteins in tissue sections by mass spectrometry. Anal Chem 76:86A-94A, 2004.
Chaurand P, Stoeckli M, Caprioli LM: Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal Chem 71:5263-5270, 1999.
Conrads TP, Fusaro VA, Ross S, et al: High-resolution serum proteomic features for ovarian cancer detection. Endocrine- Related Cancer 11:163-178, 2004.
Diamandis EP: Proteomic patterns in biological fluids: do they represent the future of cancer diagnosis? Clin Chem 49:1272- 1275, 2003.
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Garden RW, Sweedler JV: Heterogeneity within MALDI samples as revealed by mass spectrometric imaging. Anal Chem 72:30-36, 2000.
Issaq J, Conrads TP, Prieto DA, et al: SELDI TOF MS for diagnostic proteomics. Anal Chem 75:148A-155A, 2003.
Karas M, Hillenkamp F: Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60:2299-2301, 1988.
Lage H: Proteomics in cancer cell research: an analysis of therapy resistance. Pathol Res Pract 200:105-117, 2004.
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Melle C, Kaufmann R, Hommann M, et al: Proteomic profiling in microdissected hepatocellular carcinoma using protein chip® technology. Int J Oncol 24:885-891, 2004.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 178
EP 183
PG 6
ER
PT J
AU Coutts, AM
Borthwick, JN
Hungerford, LJ
Cree, AI
AF Coutts, A Michael
Borthwick, J Nicola
Hungerford, L John
Cree, A Ian
TI Post-menopausal Bleeding: a Rare Presentation of Metastatic Uveal Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE melanoma; eye; uveal; endometrium; post-menopausal bleeding; metastasis
ID melanoma; eye; uveal; endometrium; post-menopausal bleeding; metastasis
AB Uveal melanoma differs from cutaneous melanoma in many ways, including its pattern of metastasis, and exhibits latency with clinical evidence of metastasis sometimes appearing many years after primary diagnosis. Most patients develop metastasis within the liver, but some may present with metastasis to other sites. We report a case of uveal melanoma that presented with post-menopausal bleeding due to metastasis. Further investigation revealed widespread metastatic disease and the patient was not fit for chemotherapy. She died two months after presentation: autopsy revealed metastases in many sites, including the uterus, right ovarian fibroma, kidney, mesentery, liver, lung, thyroid, bone marrow and skin. The immediate cause of death was cardiac tamponade due to a malignant effusion secondary to cardiac metastasis. This case illustrates the widespread metastatic potential of uveal melanoma and highlights the potential for unusual presentation of metastatic disease from this eye tumor.
C1 [Coutts, A Michael] Preston Hall Hospital, Maidstone and Tunbridge Wells NHS Trust, Cellular PathologyKent, UK.
[Borthwick, J Nicola] University College London, Institute of Ophthalmology, Department of PathologyLondon, UK.
[Hungerford, L John] Moorfields Eye Hospital, City Road, Ocular Oncology ServiceLondon, UK.
[Cree, A Ian] University College London, Institute of Ophthalmology, Department of PathologyLondon, UK.
RP Cree, AI (reprint author), University College London, Institute of Ophthalmology, Department of Pathology, London, UK.
EM ian.cree@porthosp.nhs.uk
CR Foss AJ, Cree IA, Dolin PJ, et al: Modelling uveal melanoma. Br J Ophthalmol 83:588-594, 1999
Jensen OA: Malignant melanomas of the uvea in Denmark 1943-1952. A clinical, histopathological, and prognostic study. Acta Ophthalmol, Copenh, 43(Suppl 75):1-220, 1963
Jensen OA: Malignant melanomas of the human uvea. Recent follow-up of cases in Denmark, 1943-1952. Acta Ophthalmol, Copenh, 48:1113-1128, 1970
Sato T, Babazono A, Shields JA, et al: Time to systemic metastases in patients with posterior uveal melanoma. Cancer Invest 15:98-105, 1997
Shields JA AJ, Donoso LA, et al: Hepatic metastasis and orbital recurrence of uveal melanoma after 42 years. Am J Ophthalmol 100:666-668, 1985
Jensen OA: Malignant melanomas of the human uvea: 25-year follow-up of cases in Denmark, 1943--1952. Acta Ophthalmol, Copenh, 60:161-182, 1982
Zakka KA, Foos RY, Omphroy CA, et al: Malignant melanoma. Analysis of an autopsy population. Ophthalmology 87:549- 556, 1980
Kujala E, Makitie T, Kivela T: Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 44:4651-4659, 2003
Lee WR, Jay JL: A complicated case of ciliary body melanoma and glaucoma. Int Ophthalmol 7:175-181, 1985
Makitie T, Kivela T: Cardiac metastasis from uveal melanoma. Chest 120:2115, 2001
Rednam KR, Jampol LM, Levine RA, et al: Uveal melanoma in association with multiple malignancies. A case report and review. Retina 1:100-106, 1981
Casey JH, Shapiro RF: Metastatic melanoma presenting as primary uterine neoplasm: a case report. Cancer 33:729-731, 1974
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Berker B, Sertcelik A, Kaygusuz G, et al: Abnormal uterine bleeding as a presenting sign of metastasis to the endometrium in a patient with a history of cutaneous malignant melanoma. Gynecol Oncol 93:252-256, 2004
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Ruiz RS, El-Harazi S, Albert DM, et al: Cardiac metastasis of choroidal melanoma. Arch Ophthalmol 117:1558-1559, 1999
Chong GT, Kim RJ, Ambati SR, et al: Diagnosis of a solitary cardiac metastasis from ocular melanoma. J Thorac Cardiovasc Surg 130:1727-1728, 2005
Thombs J, Borthwick NJ, Hungerford JL, et al: Recruiting donors for autopsy based cancer research. J Med Ethics 31:360- 361, 2005
Furness PN, Nicholson ML: Obtaining explicit consent for the use of archival tissue samples: practical issues. J Med Ethics 30:561-564, 2004
McLean IW, Zimmerman LE, Evans RM: Reappraisal of Callender’s spindle a type of malignant melanoma of choroid and ciliary body. Am J Ophthalmol 86:557-564, 1978
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 184
EP 187
PG 4
ER
PT J
AU Singh, PA
Saxena, S
AF Singh, P Avninder
Saxena, Sunita
TI Infiltrating Ductal Carcinoma of the Breast, Metastatic to Axillary Lymph Nodes Harboring Primary Tuberculous Lymphadenitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE breast cancer; infiltrating ductal carcinoma; tuberculous lymphadenitis; metastasis
ID breast cancer; infiltrating ductal carcinoma; tuberculous lymphadenitis; metastasis
AB A 46-year-old female presented with lump in the left breast. Fine-needle aspiration cytology (FNAC) from breast and axillary lymph node revealed infiltrating ductal carcinoma with metastasis in axillary node. The patient underwent radical mastectomy with axillary lymph node dissection. Histopathological examination showed concomitant presence of metastatic tumor deposits and tubercular lymphadenitis in 8/18 nodes. The case is presented for its rarity and illustrates that FNAC can fail to detect mixed lesions unless multiple punctures from many sites are performed.
C1 [Singh, P Avninder] Safdarjung Hospital Campus, Institute of Pathology, 213-B Sukhdev Vihar, 110025 New Delhi, India.
[Saxena, Sunita] Safdarjung Hospital Campus, Institute of Pathology, 213-B Sukhdev Vihar, 110025 New Delhi, India.
RP Singh, PA (reprint author), Safdarjung Hospital Campus, Institute of Pathology, 110025 New Delhi, India.
EM dravninder@yahoo.co.in
CR Kaplan MH, Armstrong D, Rosen P: Tuberculosis complicating neoplastic disease: a review of 201 cases. Cancer 33: 850-858, 1974
Warthin AS: The coexistence of tuberculosis and carcinoma of the mammary gland. Am J Med Sci 118: 25, 1899
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Miller RE, Solomen PF, West JP: The co-existence of carcinoma and tuberculosis of the breast and axillary lymph nodes. Am J Surg 121: 338- 340, 1971
Das DK, Mohil RS, Kashyap V, et al: Colloid carcinoma of the breast with concomitant metastasis and a tubercular lesion in the axillary lymph nodes. A case report. Acta Cytol 36: 399-403, 1992
Pandey M, Abraham EK, Chandramohan K, Rajan B: Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: a case report. World J Surg Oncol 1: 1-3, 2003
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2006
VL 12
IS 3
BP 188
EP 189
PG 2
ER
PT J
AU Kulka, J
Tokes, AM
Kaposi-Novak, P
Udvarhelyi, N
Keller, A
Schaff, Zs
AF Kulka, Janina
Tokes, Anna-Maria
Kaposi-Novak, Pal
Udvarhelyi, Nora
Keller, Aniko
Schaff, Zsuzsa
TI Detection of HER-2/neu Gene Amplification in Breast Carcinomas Using Quantitative Real-time PCR-A Comparison with Immunohistochemical and FISH Results
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER-2/neu protein; HER-2/neu DNA amplification; breast carcinoma; immunohistochemistry; FISH; quantitative RT-PCR; LightCycler RT-PCR system
ID HER-2/neu protein; HER-2/neu DNA amplification; breast carcinoma; immunohistochemistry; FISH; quantitative RT-PCR; LightCycler RT-PCR system
AB The aim of our study was to evaluate the value of quantitative real-time-PCR (qPCR) in the determination of HER-2/neu amplification status of human breast carcinomas by comparing qPCR, FISH and immunohistochemistry results from the same samples. A total of 210 breast carcinomas were examined. Ready-to-use CB11 antibody was applied to detect HER-2/neu oncoprotein expression. In 76 out of 210 cases FISH was performed, and 162 cases were investigated with qPCR. Seventy-five tumors were 2+ or 3+ positive with immunohistochemistry, while 135 samples were either completely negative or 1+. In 45 cases results from all three methods were available. Out of these, in twenty negative and sixteen positive cases both FISH and qPCR led to similar results. The mean qPCR amplification ratio in the concordant positive cases was 5.424 while in the qPCR+/FISH- group the mean ratio was 2.765. Out of 121 samples with scores of 0 or 1+ immunohistochemical result, analyzed also with qPCR, 26 showed HER-2/neu gene amplification. In these cases the mean amplification ratio was 2.53. Comparison of FISH and qPCR together with immunohistochemistry shows that qPCR is more sensitive to detect HER-2/neu gene amplification in tumors scored as 2+ with immunohistochemistry, but the diagnostic cut-off ratio should be defined above 2.7 to avoid high number of false positive cases. Amongst the immunohistochemistry score 2+ cases, 10 of 18 showed gene amplification by qPCR while 10 of 26 by FISH. In conclusion, a well calibrated HER-2/neu qPCR assay may serve as useful alternative to FISH in breast cancer patients.
C1 [Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Kaposi-Novak, Pal] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Udvarhelyi, Nora] National Institute of OncologyBudapest, Hungary.
[Keller, Aniko] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
RP Kulka, J (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM kj@korb2.hu
CR Allred DC, Clark GM, Molina R, et al: HER-2/neu in nodenegative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 10: 599-605, 1992
Bankfalvi A, Boecker W, Reiner A: Comparison of automated and manual determination of HER2 status in breast cancer for diagnostic use: a comparative methodological study using Ventana BenchMark automated staining system and manual tests. Int J Oncol 25: 929-935, 2004
Bankfalvi A, Giuffre G, Ofner D, et al: Relationship between HER2 status and proliferation rate in breast cancer assessed by immunohistochemistry, fluorescence in situ hybridisation and standardised AgNOR analysis. Int J Oncol 23: 1285-1292, 2003
Bankfalvi A: HER-2 diagnostics. Magy Onkol 46: 11-15, 2002 [In Hungarian]
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Bartlett JM, Going JJ, Mallon EA, et al: Evaluating HER2 amplification and overexpression in breast cancer. J Pathol 195: 422-428, 2001
Beyser K, Reiser A, Gross C, et al: J. Real-time quantification of HER2/neu gene amplification by LightCycler Polymerase Chain Reaction, PCR, – a new research tool. Biochemica 2: 15-18, 2001
Beyser K, Reiser A, Gross C, et al: PCR is a powerful tool to assess HER2/neu positivity in breast cancer. Eur J Cancer 158: 419-429, 2001
Bilous M, Ades C, Armes J, et al: Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 international study. Breast 12: 92-98, 2003
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Jacobs TW, Gown AM, Yaziji H, et al: HER-2/neu protein expression in breast cancer evaluated by immunohistochemistry; a study of interlaboratory agreement. Am J Clin Pathol 113: 251-258, 2000
Jimenez RE, Wallis T, Tabasczka P, Visscher DW: Determination of Her-2/Neu status in breast carcinoma: comparative analysis of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol 13: 37-45, 2000
Kakar S, Puangsuvan N, Stevens JM, et al: HER-2/neu assessment in breast cancer by immunohistochemistry and fluorescence in situ hybridization: comparison of results and correlation with survival. Mol Diagn 5: 199-207, 2000
Kauraniemi P, Hautaniemi S, Autio R, et al: Effects of Herceptin treatment on global gene expression patterns in HER2- amplified and nonamplified breast cancer cell lines. Oncogene 23: 1010-1013, 2004
Lebeau A, Deimling D, Kaltz C, et al: Her-2/neu analysis in archival tissue samples of human breast cancer: Comparison of immunohistochemistry and in situ hybridization. J Clin Oncol 19: 354-363, 2001
Lopez-Guerrero JA, Navarro S, Noguera R, et al: Histological tumor grade correlates with HER2/c-erB-2 status in invasive breast cancer: a comparative analysis between immunohistochemical, CB11 clone and Herceptest), FISH and differential PCR procedures. Arkh Patol 65: 50-55, 2003
Lu Y, Zi X, Zhao Y, Pollak M: Overexpression of ErbB2 receptor inhibits IGF-I-induced Shc-MAPK signaling pathway in breast cancer cells. Biochem Biophys Res Commun 313: 709- 715, 2004
Luftner D, Henschke P, Kafka A, et al: Discordant results obtained for different methods of HER-2/neu testing in breast cancer – a question of standardization, automation and timing. Int J Biol Markers 19: 1-13, 2004
Ma Y, Lespagnard L, Durbecq V, et al: Polysomy 17 in HER- 2/neu status elaboration in breast cancer: effect on daily practice. Clin Cancer Res 11: 4393-4399, 2005
Nistor A, Watson PH, Pettigrew N, et al: Real-time PCR complements immunohistochemistry in the determination of HER- 2/neu status in breast cancer. BMC Clin Pathol 6:2, DOI 10.1186/1472-6890-6-2, 2006
O’Malley FP, Parkes R, Latta E, et al: Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry. Am J Clin Pathol 115: 504-511, 2001
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Riben MW, Malfetano JH, Nazeer T, et al: Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma. Mod Pathol 10: 823-831, 1997
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Slamon DJ, Godolphin W, Jones LA, et al: Studies of the HER- 2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707-712, 1989
Somerville JE, Clarke LA, Biggart JD: C-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma. J Clin Pathol 45: 16-20, 1992
Suo Z, Daehli KU, Lindboe CF, et al: Real-time PCR quantification of c-erbB-2 gene is an alternative for FISH in the clinical management of breast carcinoma patients. Int J Surg Pathol 12: 311-318, 2004
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Woods Ignatoski KM, Grewal NK, Markwart S, et al: p38MAPK induces cell surface alpha4 integrin downregulation to facilitate erbB-2-mediated invasion. Neoplasia 5:128-134, 2003
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 197
EP 204
PG 8
ER
PT J
AU Kruslin, B
Davor, T
Cviko, A
Cupic, H
Odak, L
Belicza, M
AF Kruslin, Bozo
Davor, Tomas
Cviko, Aida
Cupic, Hrvoje
Odak, Ljubica
Belicza, Mladen
TI Periacinar Clefting and p63 Immunostaining in Prostatic Intraepithelial Neoplasia and Prostatic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p63; periacinar clefting; prostatic adenocarcinoma; prostatic intraepithelial neoplasia (PIN)
ID p63; periacinar clefting; prostatic adenocarcinoma; prostatic intraepithelial neoplasia (PIN)
AB The aim of the present study was to correlate the presence and extent of retraction clefting and the expression of p63 in neoplastic glands and glands with prostatic intraepithelial neoplasia (PIN) in needle core biopsies. We analyzed needle core biopsies from 28 patients with PIN and 41 patients with adenocarcinoma. Neoplastic glands and those with PIN were analyzed on high power field (400x) and classified in three groups according to the extent of clefting. Immunohistochemical staining was performed following Microwave Streptavidin ImmunoPeroxidase (MSIP) protocol on DAKO TechMate Horizon automated immunostainer. Periacinar retraction clefting was significantly more prominent in prostatic carcinoma compared to PIN (p<0.0001) and nonneoplastic glands (p<0.0001). There was no difference between normal glands and PIN regarding clefting (p=0.8064). p63 was positive around the whole circumference in 12 out of 28 cases with PIN, and discontinuously positive in remaining 16 PIN cases suggesting initial disruption of the basal cell layer. p63 immunostaining was also positive in all nonneoplastic glands, and negative in all carcinomas. We conclude that retraction clefting was associated with cancer and lack of basal cells, but not with PIN. The relationship between clefting and p63 immunostaining in prostatic cancer should be further analyzed.
C1 [Kruslin, Bozo] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29., 10000 Zagreb, Croatia.
[Davor, Tomas] Brigham and Women’s Hospital, Department of PathologyBoston, USA.
[Cviko, Aida] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29., 10000 Zagreb, Croatia.
[Cupic, Hrvoje] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29., 10000 Zagreb, Croatia.
[Odak, Ljubica] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29., 10000 Zagreb, Croatia.
[Belicza, Mladen] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29., 10000 Zagreb, Croatia.
RP Kruslin, B (reprint author), University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, 10000 Zagreb, Croatia.
EM bkruslin@kbsm.hr
CR Bostwick DG, Dundore PA: Biopsy pathology of the prostate. Chapmann&Hall Medical, London, 1997.
Bostwick DG, Qian J: High-grade prostatic intraepithelial neoplasia. Mod Pathol 17: 360-379, 2004.
Davis LD, Zhang W, Merseburger A, et al: p63 expression profile in normal and malignant prostate epithelial cells. Anticancer Res 22: 3819-3825, 2002.
De Marzo AM, Meecker AK, Zha S, et al: Human cancer precursors and pathobiology. Urology 62(Suppl 1): 55-62, 2003.
Epstein JI: Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy. Mod Pathol 17: 307-315, 2004.
Epstein JI: Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy. Pathol International 54(Suppl 1): S609-S612, 2004.
Epstein JI: The diagnosis and reporting of adenocarcinoma of the prostate in core needle biopsy specimens. Cancer 78: 350- 356, 1996.
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Kru lin B, Tomas D, Rogatsch H, et al: Correlation of periacinar retraction clefting in needle core biopsies and corresponding prostatectomy specimens of patients with prostatic adenocarcinoma. Int J Surg Pathol 13: 67-72, 2005.
Leroy X, Aubert S, Villers A, et al: Minimal focus of adenocarcinoma on prostate biopsy: clinicopathologic correlations. J Clin Pathol 56: 23-32, 2003.
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Oliai BR, Kahane H, Epstein JI: Can basal cells be seen in adenocarcinoma of the prostate?: an immunohistochemical study using high molecular weight cytokeratin, clone 34 beta E12, antibody. Am J Surg Pathol 26: 1151-1160, 2002.
Parsa R, Yang A, McKeon F, Green H: Association of p63 with proliferative potential in normal and neoplastic human keratinocytes. J Invest Dermatol 113: 1099-1105, 1999.
Rogatsch H, Mairinger T, Horninger W, et al: Optimized preembedding method improves the histologic yield of prostatic core needle biopsies. Prostate 42: 124-129, 2000.
Rogatsch H, Moser P, Volgger H, et al: Diagnostic effect of an improved preembedding method of prostate needle biopsy specimens. Hum Pathol 31: 1102-1107, 2000.
Sakr WA: Prostatic intraepithelial neoplasia. Pathol International 54(Suppl 1):S612-S615, 2004.
Signoretti S, Waltregny W, Dilks J, et al: p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157: 1769-1775, 2000.
Tacha DE, Miller RT: Use of p63/P504S monoclonal antibody cocktail in immunohistochemical staining of prostate tissue. Appl Immunohistochem Mol Morphol 12: 75-78, 2004.
Tomas D, Kru lin B: The potential value of, myo)fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma. Prostate 61: 324-331, 2004.
Varma M, Jasani B: Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature. Histopathology 47: 1-16, 2005.
Varma M, Lee MW, Tamboli P, et al: Morphologic criteria for the diagnosis of prostatic adenocarcinoma in needle biopsy specimens. Arch Pathol Lab Med 126: 554-561, 2002.
Weinstein MA, Signoretti S, Loda M: Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. Mod Pathol 15: 1302-1308, 2002.
Zhou M, Shah R, Shen R, Rubin MA: Basal cell cocktail, 34betaE12 + p63, improves the detection of prostate basal cells. Am J Surg Pathol 27: 365-371, 2003.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 205
EP 209
PG 5
ER
PT J
AU Sahin, IF
Yilmaz, Z
Yagmurdur, CM
Atac, BF
Ozdemir, HB
Karakayali, H
Demirhan, B
Haberal, M
AF Sahin, Iffet Feride
Yilmaz, Zerrin
Yagmurdur, Can Mahmut
Atac, Belgin Fatma
Ozdemir, Handan Binnaz
Karakayali, Hamdi
Demirhan, Beyhan
Haberal, Mehmet
TI Clinical Findings and HER-2/neu Gene Amplification Status of Breast Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER-2/neu; breast carcinoma; FISH
ID HER-2/neu; breast carcinoma; FISH
AB The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.
C1 [Sahin, Iffet Feride] Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, 06570 Ankara, Turkey.
[Yilmaz, Zerrin] Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, 06570 Ankara, Turkey.
[Yagmurdur, Can Mahmut] Baskent University Faculty of Medicine, Department of SurgeryAnkara, Turkey.
[Atac, Belgin Fatma] Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, 06570 Ankara, Turkey.
[Ozdemir, Handan Binnaz] Baskent University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Karakayali, Hamdi] Baskent University Faculty of Medicine, Department of SurgeryAnkara, Turkey.
[Demirhan, Beyhan] Baskent University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Haberal, Mehmet] Baskent University Faculty of Medicine, Department of SurgeryAnkara, Turkey.
RP Sahin, IF (reprint author), Baskent University Faculty of Medicine, Department of Medical Biology and Genetics, 06570 Ankara, Turkey.
EM feridesahin@hotmail.com
CR Dandachi N, Dietze O, Hauser-Kronberger C: Chromogenic in situ hybridization: a novel approach to a practical and sensitive method for the detection of HER2 oncogene in archival human breast carcinoma. Lab Invest 82: 1007-1014, 2002.
Mariani SM: Conference report - breast cancer markers: What Next? Medscape General Medicine 5: 2003.
Dowsett M, Bartlett J, Ellis IO et al: Correlation between immunohistochemistry, HercepTest, for HER-2 in 426 breast carcinomas from 37 centres. J Pathol 199: 418-423, 2003.
Sauer T, Wiedswang G, Boudjema G et al: Assessment of HER- 2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice? APMIS 111: 444-450, 2003.
Varshney D, Zhou YY, Geller SA et al: Determination of HER- 2 status and chromosome 17 polisomy in breast carcinomas comparing HercepTest and PathVysion FISH assay. Am J Clin Pathol 121: 70-77, 2004.
Simeone A: Detection of mRNA in tissue section with radiolabelled riboprobes. In: In Situ Hybridization 2nd ed, Ed: DG Wilkinson), The Practical Approach Series, Oxford University Press, 1998, pp 69-86.
Yilmaz Z, Sahin FI, Atalay B, et al: Chromosome 1p36 and 22qter deletions in paraffin block sections of intracranial meningiomas. Pathol Oncol Res 11: 224-228, 2005.
Tibiletti MG: Specificity of interphase fluorescence in situ hybridization for detection of chromosome aberrations in tumor pathology. Cancer Genet Cytogenet 155: 143-148, 2004.
Sumita G, Zoran G, Amin M et al: FISH for HER-2/neu in breast cancer: Standardization makes the difference! Ind J Cancer 41: 152-158, 2004.
Bozzetti C, Nizzoli R, Guazzi A et al: HER-2/neu amplification detected by fluorescence in situ hybridization in fine needle aspirates from primary breast cancer. Ann Oncol 13: 1398- 1403, 2002.
Bartlett J, Mallon E, Cooke T: The clinical evaluation of HER- 2 status: which test to use? J Pathol 199: 411-417, 2003.
Pauletti G, Dandekar S, RongHM et al: Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: A direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol 18: 3651-3664, 2000.
Ross JS, Fletcher JA, Linette GP et al: The HER-2/neu gene and protein in breast cancer 2003: Biomarker and target of therapy. The Oncologist 8: 307-325, 2003.
Climent MA, Segui MA, Peiro G et al: Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment. The Breast 10: 67-77, 2001.
Dowsett M, Harper-Wynne C, Boeddinghaus I et al: HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer. Cancer Res 61: 8452-8458, 2001.
Elledge RM, Green S, Ciocca D et al: HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study. Clin Cancer Res 4: 7- 12, 1998.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 211
EP 215
PG 5
ER
PT J
AU Cserni, G
Orosz, Zs
Kulka, J
Sapi, Z
Kalman, E
Bori, R
AF Cserni, Gabor
Orosz, Zsolt
Kulka, Janina
Sapi, Zoltan
Kalman, Endre
Bori, Rita
TI Divergences in Diagnosing Nodular Breast Lesions of Noncarcinomatous Nature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE fibroepithelial breast tumors; nodular lesions; phyllodes tumor; phylloid tumor; fibroadenoma
ID fibroepithelial breast tumors; nodular lesions; phyllodes tumor; phylloid tumor; fibroadenoma
AB Nodular breast lesions of noncarcinomatous origin are often of fibroepithelial origin. They may cause classification problems when they are hypocellular or hypercellular; the latter setting may also raise the differential diagnosis of phyllodes tumors. Thirty equivocal nodular breast lesions were collected and one hematoxylin and eosin slide from each was assessed by six pathologists with special interest in breast pathology. The overall reproducibility of classifying these lesions into categories of fibroadenoma, phyllodes tumor or anything else was moderate (kappa value: 0.48). The lack of a uniform nomenclature was not felt disturbing for hypocellular lesions, but the discordant diagnosis of tumors resembling or representing phyllodes tumors was acknowledged to require intervention, such as more obvious implication of guidelines and quality assurance programs aiming at assessing diagnoses and prognostic parameters.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Department of Diagnostic PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Sapi, Zoltan] St John's Hospital, Department of PathologyBudapest, Hungary.
[Kalman, Endre] University of Pecs, Department of PathologyPecs, Hungary.
[Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Azzopardi J: Problems in breast pathology. Saunders, London- Philadelphia-Toronto, 1979
Bellocq JP, Magro G: Fibroepithelial tumors. In: WHO Classification of Tumors. Pathology and Genetics of Tumors of the Breast and Female Genital Organs., Eds: Tavassoli FA, Devilee P), IARC Press, Lyon, 2003, pp 99-103
Berean K, Tron VA, Churg A, et al: Mammary fibroadenoma with multinucleated stromal giant cells. Am J Surg Pathol 10: 823-827, 1986
Chen WH, Cheng SP, Tzen CY, et al: Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol 91: 185-194, 2005
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Ellis IO, Pinder SE, Bobrow L, et al: Pathology reporting of breast disease. NHS Publication No 58. NHS Cancer Screening Programmes and the Royal College of Pathologists, Sheffield, 2005
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Kuijper A, Buerger H, Simon R, et al: Analysis of the progression of fibroepithelial tumors of the breast by PCR-based clonality assay. J Pathol 197: 575-581, 2002
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Putti TC, Pinder SE, Elston CW, et al: Breast pathology practice: most common problems in a consultation service. Histopathology 47: 445- 457, 2005
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Rosen PP: Rosen’s Breast Pathology, 2nd edition. Lippincott, Williams and Wilkins, Philadelphia, 2001
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 216
EP 221
PG 6
ER
PT J
AU Kiani, J
Khan, A
Khawar, H
Shuaib, F
Pervez, Sh
AF Kiani, Jawad
Khan, Afrasyab
Khawar, Hina
Shuaib, Fawad
Pervez, Shahid
TI Estrogen Receptor Alpha-Negative and Progesterone Receptor-Positive Breast Cancer: Lab Error or Real Entity?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE estrogen receptor (ER) alpha; progesterone receptor (PR); breast carcinoma
ID estrogen receptor (ER) alpha; progesterone receptor (PR); breast carcinoma
AB Aretrospective study comparing the estrogen receptor (ER) alpha subtype and progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over 2.5 years was carried out. Strictly speaking it is generally believed that breast carcinomas can biochemically express PR only if they are ER-positive. However, a few ERalpha-PR+ cases do exist paradoxically. This class of tumors was the focus of our study in which we looked at the possible reasons for such an immunophenotype and compared it with a group of ERalpha+PR+ breast carcinomas. An internationally recognized immunohistochemical method employing monoclonal antibodies against estrogen and progesterone receptors was used. Correlations with established risk factors i.e. menopausal status, grade, tumor size and lymph node status were analyzed for our study group (ERalpha-PR+) and compared with a control (ERalpha+PR+). Out of the total 1625 cases, 29.91% (486) were ERalpha+PR+, 5.11% (83) were ERalpha+PR-, 56.86% (924) were ERalpha-PR- and 8.12% (132) were ERalpha-PR+. Patients’ age was significantly lower in the ERalpha-PR+ group (P=0.002). Statistical analysis of the grading between the two study groups revealed no significant difference (P=0.091), although the ERalpha-PR+ group contained significantly more poorly differentiated tumors than the ERalpha+PR+ one (P=0.032). Tumor size was also significantly larger in the ERalpha-PR+ than in the ERalpha+PR+ group (P=0.046). The frequency of lymph node metastases was independent of receptor profile. In conclusion, our study group does exhibit characteristics which are suggestive of a distinct breast cancer phenotype (ERalpha-PR+) with a different etiology and prognosis.
C1 [Kiani, Jawad] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
[Khan, Afrasyab] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
[Khawar, Hina] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
[Shuaib, Fawad] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
RP Pervez, Sh (reprint author), The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
EM shahid.pervez@aku.edu
CR Ballare C, Bravo, AI, Sorin I, et al: The expression of progesterone receptors coincides with an arrest of DNA synthesis in human breast cancer. Cancer 67: 1352-1358, 1991
Berger U, McLelland RA, Wilson P, et al: Immunohistochemical determination of estrogen receptor, progesterone receptor and 1, 25-dihydroxvitamin D3 receptor in breast cancer and relationship to prognosis. Cancer Res 51: 239-244, 1991
Berkenstam A, Glaumann H, Martin M, et al: Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47Dco and MCF-7 breast cancer cells. Mol Endocrinol 3: 22- 28, 1989
Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11:359-377, 1957
deSombre, ER: Steroid receptors in breast cancer. In: The Breast., Eds: McDivitt RW, Oberman HA, Ozello L and Kaufman N), Williams and Wilkins, Baltimore, 1984, pp149-174
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Fishman J, Nisselbaum JS, Menendez-Botet CJ, Schwartz MK: Estrogen and estradiol content in human breast tumors: relationship to estradiol receptors. J Steroid Biochem 8: 893-896, 1977
Greene GL, Press MF: Steroid receptor structure, including monoclonal antibodies and new methods of determination): structure and dynamics of the estrogen receptor. J Steroid Biochem 24: 1-7, 1986
Greene GM, Fitch FW, Jensen EV: Monoclonal antibodies to trophilin: probes for the study of estrogen receptors. Proc Natl Acad Sci USA 77: 157-161, 1980
Horwitz KB, McGuire WL: Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem 253: 2223-2228, 1978
Horwitz KB: Cellular heterogeneity and mutant oestrogen receptors in hormone resistant breast cancer. Cancer Surv 14: 41-54, 1992
Howat JMT, Harris M, Swindell R, Barnes DM: The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast. Br J Cancer 51: 263-270, 1985
Kiang DT, Kollander R: Breast cancers negative for estrogen receptor but positive for progesterone receptor, a true entity? J Clin Oncol 5: 662-666, 1987
Leclercq G, Heuson JC, Deboel MC, et al: Estrogen and progesterone receptors in human breast cancer. In: Progesterone Receptors in Normal and Neoplastic Tissues., Eds: McGuire WL, Raynaud J-P, Baulieu E-E), Raven, New York, 1977, pp 141-153
Leygue E, Dotzlaw H, Watson PH, Murphy LC: Altered estrogen receptor alpha and beta messenger RNA expression during human breast tumorigenesis. Cancer Res 58: 3197-3201, 1998
McGuire WL: Hormone receptors. Their role in predicting prognosis and response to endocrine therapy. Semin Oncol 5: 428-433, 1979
McGuire WL, Horwitz KB, Pearson DH, Segaloff A: Current status of estrogen and progesterone receptors in breast cancer. Cancer 39: 2934-2947, 1977
McGuire WL: Steroid receptors in human breast cancer. Cancer Res 38: 4289-4291, 1978
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Pichon MF, Milgrom E: Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumors. Br J Cancer 65: 895-897, 1992
Reiner A, Neumeister B, Spona J, et al: Immunocytochemical localization of estrogen and progestin and prognosis in human primary breast cancer. Cancer Res 50: 7057-7061, 1990
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Sarrif AM, Durant JR: Evidence that estrogen-receptor-negative progesterone-receptor-positive breast and ovarian carcinomas contain estrogen receptor. Cancer 48: 1215-1220, 1982
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Shaaban AM, O’Neill PA, Davies MP, et al: Declining estrogen receptor beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 27: 1502-1512, 2003
Shapiro CM, Schiffeling D, Bitran JD, et al: Prognostic value of estrogen receptor value in pathologic stage 1 and 2 adenocarcinoma of the breast. J Surg Oncol 19: 119-121, 1982
Shigehira S, Makiko H, Masakazu T: Clinical significance of estrogen receptor β in breast cancer. Cancer Chemother Pharmacol 56: s21-s26, 2005
Speirs V, Skliris GP, Burdall SE, Carder PJ: Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol 55: 371-374, 2002
Thorpe SM: Immunological quantitation of nuclear receptors in human breast cancers: relation to cytosolic estrogen and progesterone receptors. Cancer Res 47: 1830-1835, 1987
Thorsen T: Occupied and unoccupied oestradiol receptor in human breast tumor cytosol. J Steroid Biochem. 24: 1-7, 1986
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 223
EP 227
PG 5
ER
PT J
AU Kamory, E
Tanyi, M
Kolacsek, O
Olasz, J
Toth, L
Damjanovich, L
Csuka, O
AF Kamory, Eniko
Tanyi, Miklos
Kolacsek, Orsolya
Olasz, Judit
Toth, Laszlo
Damjanovich, Laszlo
Csuka, Orsolya
TI Two Germline Alterations in Mismatch Repair Genes Found in a HNPCC Patient with Poor Family History
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bethesda criteria; hereditary nonpolyposis colorectal cancer; hMLH1; hMSH2; microsatellite instability; immunohistochemistry
ID Bethesda criteria; hereditary nonpolyposis colorectal cancer; hMLH1; hMSH2; microsatellite instability; immunohistochemistry
AB The Bethesda guidelines may offer more useful criteria in patients’ selection for germline mismatch repair gene mutation analysis than guidelines merely based on family background. An early onset double primary colorectal cancer patient with poor family history with MSI-H status was investigated for MLH1 promoter methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and mutations in the MLH1 and MSH2 genes. The index patient carried two germline alterations, the p.Val716Met in MLH1 and the c.2210+1G>C in MSH2 genes, and both tumors failed to express MLH1 and MSH2 proteins. After subsequent analysis of the whole family of the index patient, the p.Val716Met variant can be defined as a rare polymorphism with the possible contribution of pathogenicity to tumor formation and c.2210+1G>C as a true pathogenic mutation causing an out-of-frame deletion of exon 13.
C1 [Kamory, Eniko] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Tanyi, Miklos] University of Debrecen, Medical and Health Science Centre, 1st Department of SurgeryDebrecen, Hungary.
[Kolacsek, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Olasz, Judit] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Damjanovich, Laszlo] University of Debrecen, Medical and Health Science Centre, 1st Department of SurgeryDebrecen, Hungary.
[Csuka, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Kamory, E (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, H-1122 Budapest, Hungary.
EM eniko.kamory@gmail.com
CR Cunningham JM, Christensen ER, Tester DJ, et al: Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58: 3455-3460, 1998.
Wang Q, Lasset C, Desseigne F, et al: Prevalence of germline mutations of hMLH1, hMLS2, hPMS1, hPMS2, and hMSH6 genes in French kindreds with nonpolyposis colorectal cancer. Hum Genet 105: 79-85, 1999.
Syngal S, Fox EA, Eng C, et al: Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet 37: 641-645, 2000.
Rodriguez-Bigas MA, Boland CR, Hamilton SR, et al: A National Institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 89: 1758-1762, 1997.
Raedle J, Trojan J, Brieger A, et al: Bethesda guidelines: Relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer. Ann Intern Med 135: 566-576, 2001.
Montera M, Resta N, Simone C, et al: Mutational germline analysis of hMSh2 and hMLH1 genes in early onset colorectal cancer patients. J Med Genet 37: E7, 2000.
Boland CR, Thibodeau SN, Hamilton SR, et al: A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58: 5248-5257, 1998.
Kamory E, Kolacsek O, Otto S, et al: hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients. Pathol Oncol Res 9: 236-241, 2003.
Eads CA, Lord RV, Wickramasinghe K, et al: Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Res 61: 3410-3418, 2001.
Beck NE, Tomlinson IPM, Homfray T, et al: Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria. Hum Genet 99: 219-224, 1997.
Yanagisawa Y, Akiyama Y, Iida S, et al: Methylation of the hMLH1 promoter in familial gastric cancer with microsatellite instability. Int J Cancer 85: 50-53, 2000.
Wahlberg SS, Schmeits J, Thomas G, et al: Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 62: 3485- 3492, 2002.
Hendriks Y, Franken P, Dierssen JW, et al: Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. Am J Pathol 162: 469-477, 2003.
Raut CP, Pawlik TM, Rodriguez-Bigas MA: Clinicopathologic features in colorectal cancer patients with microsatellite instability. Mut Res. 568:275-282, 2004.
Hutter P, Couturier A, Membrez V, et al: Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer. Int J Cancer 78: 80-84, 1998.
Cederquist K, Emanuelsson M, Goransson I, et al: Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden. Int J Cancer 109: 370-376, 2004.
http://prodes.toulouse.inra.fr
Kurzawski G, Suchy J, Kladny J, et al: Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States. J Med Genet 39: E65, 2002.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 228
EP 233
PG 6
ER
PT J
AU Sule, N
Teszas, A
Kalman, E
Szigeti, R
Miseta, A
Kellermayer, R
AF Sule, Norbert
Teszas, Alexandra
Kalman, Endre
Szigeti, Reka
Miseta, Attila
Kellermayer, Richard
TI Lithium Suppresses Epidermal SERCA2 and PMR1 Levels in the Rat
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hailey-Hailey disease; Darier disease; lithium; rat; SERCA2; PMR1
ID Hailey-Hailey disease; Darier disease; lithium; rat; SERCA2; PMR1
AB Autosomal dominant mutations in the genes encoding the calcium ATPases SERCA2 and PMRI/SPCA1 cause the genodermatoses Darier disease (DD) and Hailey-Hailey disease (HHD), respectively. Recent observations indicated that the level of the pathogenic proteins greatly decreases in the affected areas of the epidermis in these disorders. Here we addressed how lithium, a recognized exacerbating factor in Darier disease, affects the epidermal expression of SERCA2 and PMR1/SPCA1 in the rat as a model. Standard histologic and immunohistochemical methods were utilized in 3 lithium-treated and 3 control animals. A significant suppression of epidermal SERCA2 and PMR1 levels were observed as a result of lithium therapy in addition to marked qualitative and quantitative changes in the stratum corneum and the granular layer of the epidermis in the treated animals. Our findings suggest that exacerbating factors in calcium ATPase disorders of the skin suppress epidermal SERCA2 and PMR1 levels, further decreasing the already haploinsufficient protein expression to a potentially critical level in Darier disease and Hailey-Hailey disease, respectively. Lithium therapy should specifically be avoided not only in Darier disease, but Hailey-Hailey disease as well.
C1 [Sule, Norbert] University of Pecs, Department of PathologyPecs, Hungary.
[Teszas, Alexandra] University of Pecs, Department of Medical Genetics and Child Development, Jozsef A. u. 7., H-7623 Pecs, Hungary.
[Kalman, Endre] University of Pecs, Department of PathologyPecs, Hungary.
[Szigeti, Reka] University of Pecs, Department of Dermatology, Venereology and OncodermatologyPecs, Hungary.
[Miseta, Attila] University of Pecs, Department of Laboratory MedicinePecs, Hungary.
[Kellermayer, Richard] University of Pecs, Department of Medical Genetics and Child Development, Jozsef A. u. 7., H-7623 Pecs, Hungary.
CR Sakuntabhai A, Ruiz-Perez V, Carter S, et al: Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 21: 271-277, 1999
Hu Z, Bonifas JM, Beech J, et al: Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet 24: 61-65, 2000
Tavadia S, Authi KS, Hodgins MB, Munro CS: Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease. Br J Dermatol 151: 440-445, 2004
Porgpermdee S, Yu X, Takagi A, et al: Expression of SPCA1, Hailey-Hailey disease gene product, in acantholytic dermatoses. J Dermatol Sci 40: 137-140, 2005
Mayuzumi N, Ikeda S, Kawada H, et al: Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. Br J Dermatol 152: 697-701, 2005
Rubin MB: Lithium-induced Darier's disease. J Am Acad Dermatol 32: 674-675, 1995
Kellermayer R: Hailey-Hailey disease as an orthodisease of PMR1 deficiency in Saccharomyces cerevisiae. FEBS Lett 579: 2021-2025, 2005
Prasad V, Boivin GP, Miller ML, et al: Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+- ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer Res 65: 8655-8661, 2005
Burge SM, Schomberg KH: Adhesion molecules and related proteins in Darier's disease and Hailey-Hailey disease. Br J Dermatol 127: 335-343, 1992
Elias PM, Nau P, Hanley K, et al: Formation of the epidermal calcium gradient coincides with key milestones of barrier ontogenesis in the rodent. J Invest Dermatol 110: 399-404, 1998
Green E, Elvidge G, Jacobsen N, et al: Localization of bipolar susceptibility locus by molecular genetic analysis of the chromosome 12q23-q24 region in two pedigrees with bipolar disorder and Darier's disease. Am J Psychiatry 162: 35-42, 2005
Kellermayer R, Szigeti R, Keeling KM, et al: Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey- Hailey disease. J Invest Dermatol 126: 229-231, 2006
Yeung CK, Chan HH: Cutaneous adverse effects of lithium: epidemiology and management. Am J Clin Dermatol 5: 3-8, 2004
Csutora P, Karsai A, Nagy T, et al: Lithium induces phosphoglucomutase activity in various tissues of rats and in bipolar patients. Int J Neuropsychopharmacol 9:613-619, 2006
Csutora P, Strassz A, Boldizsar F, et al: Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae. Am J Physiol Cell Physiol 289: C58-C67, 2005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 234
EP 236
PG 3
ER
PT J
AU Alberth, M
Majoros, L
Kovalecz, G
Borbas, E
Szegedi, I
J Marton, I
Kiss, Cs
AF Alberth, Marta
Majoros, Laszlo
Kovalecz, Gabriella
Borbas, Emese
Szegedi, Istvan
J Marton, Ildiko
Kiss, Csongor
TI Significance of Oral Candida Infections in Children with Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE child; cancer; oral infection; Candida albicans; non-albicans Candida strains
ID child; cancer; oral infection; Candida albicans; non-albicans Candida strains
AB Candidiasis is common in children with cancer, particularly during periods of severe immunosuppression and neutropenia. Our aim was to study the microbiological changes in the oral cavity of children with newly diagnosed cancer. The study group consisted of 30 consecutive children and adolescents, 16 with acute lymphoblastic leukemia and 14 with solid tumors. Oral cultures to detect fungi and bacteria were conducted for all patients before treatment, during and after neutropenic episodes. In 23 patients developing fever simultaneous throat, urine and blood sampling was carried out. No pathogens were found in the cultures taken before the outset (30 cultures) or after recovery from (30 cultures) the neutropenic episodes. In the 45 oral cultures taken during the neutropenic episodes 38 (84.4%) proved positive. Fungi were the most frequently isolated oral pathogens: 33/38 yeast and 6/38 bacterial infections were identified. There was no association between the underlying malignancy and the occurrence of the positive cultures. Of the 30 patients, all 23 (76.7%) who have developed moderate-to-severe neutropenia, developed oral fungal colonization or clinically obvious fungal infection at least on one occasion during the study. In addition to oral samples, fungi were identified in 9/23 pharyngeal swabs, 6/23 urine and 1/23 blood cultures. The initial fungal pathogen was exclusively (33/33) Candida albicans. In extended severe neutropenic states, C. albicans was replaced by non-albicans species (C. kefyr, C. lusitaniae, C. sake, C. tropicalis) in 5 patients between 4 to 6 days of the neutropenic episodes. Four of the nonalbicans Candida strains were resistant to azole-type antifungal agents. Neutropenic episodes of children with cancer are associated with an increased risk of developing oral and even systemic infections with C. albicans that can be replaced by azole-resistant nonalbicans strains in prolonged neutropenia contributing to morbidity of these patients.
C1 [Alberth, Marta] University of Debrecen, Faculty of DentistryDebrecen, Hungary.
[Majoros, Laszlo] University of Debrecen, Faculty of Medicine, Department of Medical MicrobiologyDebrecen, Hungary.
[Kovalecz, Gabriella] University of Debrecen, Faculty of DentistryDebrecen, Hungary.
[Borbas, Emese] University of Debrecen, Faculty of DentistryDebrecen, Hungary.
[Szegedi, Istvan] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei krt., H-4032 Debrecen, Hungary.
[J Marton, Ildiko] University of Debrecen, Faculty of DentistryDebrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei krt., H-4032 Debrecen, Hungary.
RP Kiss, Cs (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4032 Debrecen, Hungary.
EM kisscs@dote.hu
CR Ball K, Sweeney MP, Baxter WP, Bagg J: Fluconazole sensitivity of Candida species isolated from the mouth of terminally ill cancer patients. Am J Hosp Palliat Care 15: 315-319, 1998
Dahiya MC, Redding SW, Dahiya RS, et al: Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 57: 79-83, 2003
Davies AN, Brailsford S, Broadley K, Beighton D: Oral yeast carriage in patients with advanced cancer. Oral Microbiol Immunol 17: 79-84, 2002
Edwards JE Jr: Editorial response: Should all patients with Candidemia be treated with antifungal agents? Clin Infect Dis 15: 422-423, 1992
Epstein JB, Hancock PJ, Nantel S: Oral candidiasis in hematopoietic cell transplantation patients: an outcome-based analysis. Oral Surg Oral Med Oral Pathol Radiol Endod 96: 154-163, 2003
Epstein JB, Ransier A, Lunn R, et al: Prophylaxis of candidiasis in patients with leukemia and bone marrow transplants. Oral Surg Oral Med Oral Pathol Radiol Endod 81: 291-296, 1996
Genc A, Atalay T, Gedikoglu G, et al: Leukemic children: clinical and histopathological gingival lesions. J Clin Pediatr Dent 22: 253-256, 1998
Gozdasoglu S, Ertem M, Buyukkececi Z, et al: Fungal colonization and infection in children with acute leukemia and lymphoma during induction therapy. Med Pediatr Oncol 32: 76-77, 2000
Hoppe JE, Klausner M, Klingebiel T, Niethammer D: Retrospective analysis of yeast colonization and infection in pediatric bone marrow transplant recipients. Mycoses 40: 47-54, 1997
Hughes WT: Systemic candidiasis: a study of 109 fatal cases: Pediatr Infect Disease J 1: 11-18, 1982
Michaud M, Baehner RL, Bixler D, Kafrawy AH: Oral manifestations of acute leukemia in children. J Am Dent Assoc 95: 1145-1150, 1977
Ridola V, Chachaty E, Raimondo G, et al: Candida infections in children with conventional chemotherapy for solid tumors, transplant recipients excluded): The Institute Gustave Roussy Pediatrics Department experience. Pediatr Blood Cancer 42: 332-337, 2004
Simon AR, Roberts MW: Management of oral complications associated with cancer therapy in pediatric patients. J Dent Child 58: 384-398, 1991
Sonis ST, Fey EG: Oral complications of cancer therapy. Oncology, Williston Park, 16: 680-686, 2002
Stinnet EA, Childers NK, Wright JT, et al: The detection of oral Candida in pediatric leukemia patients. Pediatr Dent 14: 236- 239, 1992
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 237
EP 241
PG 5
ER
PT J
AU Derecskei, K
Moldvay, J
Bogos, K
Timar, J
AF Derecskei, Katalin
Moldvay, Judit
Bogos, Krisztina
Timar, Jozsef
TI Protocol Modifications Influence the Result of EGF Receptor Immunodetection by EGFR pharmDxTM in Paraffin-Embedded Cancer Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE EGF receptor immunodetection; EGFR pharmDx; antigen retrieval; incubation time
ID EGF receptor immunodetection; EGFR pharmDx; antigen retrieval; incubation time
AB EGF receptor (EGFR) became a useful target for several recently introduced therapies of various cancer types including colorectal, lung, head and neck cancers and glioblastoma. The successful clinical application of these novel molecularly targeted therapies requires the expression of their target, EGFR, determined by nucleic acid based or immunohistochemical techniques. However, until now, immunohistochemistry has not become a reliable diagnostic approach for this purpose. The golden standard for the determination of EGFR protein expression in paraffin-embedded cancer tissues is the EGFR pharmDxTM kit. Here we show that the recommended protocol may not be optimal for EGFR immunodetection. Microwave antigen retrieval and extended primary antibody incubation time converted four out of eight EGFR-negative tumors into EGFR-positive in a study of 50 lung adenocarcinoma cases. Accordingly, we recommend retesting cases negative for EGFR with EGFR pharmDxTM using protocol modifications optimizing antigen retrieval and the incubation periods.
C1 [Derecskei, Katalin] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Moldvay, Judit] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Baselga J and Arteaga CL: Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445-2459, 2005
Meropol NJ: Epidermal growth factor receptor inhibitors in colorectal cancer: it’s time to get back on target. J Clin Oncol 23:1791-1793, 2005
http://www.fda.gov/cdrh/mda/docs
http://www.ventanamed.com/catalog/antibody
Nguyen PL, Swanson PE, Jaszcz W, et al: Expression of epidermal growth factor receptor in invasive transitional cell carcinoma of the urinary bladder. A multivariate survival analysis. Am J Clin Pathol 101:166-176, 1994
Pii K, Andersen FG, Jensen S, Spaulding B: Characterization of a new monoclonal antibody, clone 2-18C9, for the measurement of epidermal growth factor receptor expression in solid tumor. Proc. 95th AACR, Abstr #5029, 2004
Harari PM and Huang S-M: Searching for reliable epidermal growth factor receptor response predictors. Clin Cancer Res 10:428-432, 2004
Dancey JE: Predictive factors for epidermal growth factor receptor inhibitors. The bull’s-eye hits the arrow. Cancer Cell 5:411-415, 2004
Bunn PA Jr, Dziadziuszko R, Varella-Garcia M, et al: Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res 12:3652-3656, 2006
Chung KY, Shia J, Kemeny NE, et al: Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803-1810, 2005
Baselga J, Trigo JM, Bourhis J, et al: Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 23:5568-5577, 2005
Robert F, Blumenschein G, Herbst RS, et al: Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer. J Clin Oncol 23:9089-9096, 2005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 243
EP 246
PG 4
ER
PT J
AU Pappa, L
Machera, M
Tsanou, E
Damala, C
Peschos, D
Bafa, M
Malamou-Mitsi, V
AF Pappa, Lina
Machera, Melpomeni
Tsanou, Eleni
Damala, Constantina
Peschos, Dimitrios
Bafa, Maria
Malamou-Mitsi, Vassiliki
TI Subcutaneous Metastasis of Peritoneal Mesothelioma Diagnosed by Fine-Needle Aspiration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE mesothelioma; metastatic nodules; FNA; cytology
ID mesothelioma; metastatic nodules; FNA; cytology
AB Mesothelioma is a rare malignant neoplasm of the serosal membranes, which can give distant metastases in various organs in advanced stages of its course. Subcutaneous tissue is an unusual metastatic site. In the literature, only one case of metastatic mesothelioma to the skin of the face has been reported. We present a case of a 60-year-old female with a prior history of peritoneal malignant mesothelioma, who 6 months after the initial diagnosis presented with a subcutaneous nodule in the lateral chest wall. Cytological examination of the material obtained by FNA from the nodule revealed metastatic mesothelioma. Although subcutaneous metastasis of malignant mesothelioma is a rare entity, one must always keep this possibility in mind and proceed to further investigation of such lesions. In these cases, FNA is a simple diagnostic procedure for the identification of metastatic disease in patients with a prior history of malignancy.
C1 [Pappa, Lina] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
[Machera, Melpomeni] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
[Tsanou, Eleni] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
[Damala, Constantina] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
[Peschos, Dimitrios] University of Ioannina, Department of Forensic Medicine and ToxicologyIoannina, Greece.
[Bafa, Maria] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
[Malamou-Mitsi, Vassiliki] Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
RP Malamou-Mitsi, V (reprint author), Ioannina University Hospital, Department of Pathology, 45110 Ioannina, Greece.
EM me00627@cc.uoi.gr
CR Ansari N, Derias N: Diagnosis of malignant mesothelioma by fine needle aspiration of a cervical lymph node. A case report. Acta Cytol 44: 70-74, 2000
Antman K: Natural history and epidemiology of malignant mesothelioma. Chest 103, Suppl): 373-376, 1993
Battifora H, Kopinski M: Distinction of mesothelioma from adenocarcinoma: an immunohistochemical approach. Cancer 55: 1679-1685, 1985
Brenner J, Sordillo P, Magill G, Golbey R: Malignant mesothelioma of the pleura: Review of 123 patients. Cancer 49: 2431- 2435, 1982
Chabot J, Beard D, Langlois A. Mesotheliomas of peritoneum epicardium and pericardium induced by strain of MC29 avian leucosis virus. Cancer Res 30: 1287-1308, 1970
Constantopoulos S, Goudevenos J, Saratzis N, et al: Pleural calcification and restrictive lung function in Northwestern Greece. Environ Res 38: 319-331, 1985
Constantopoulos S, Malamou-Mitsi V, Goudevenos J, et al: High incidence of malignant pleural mesothelioma in neighbouring villages of Northwestern Greece. Respiration 51: 266- 271, 1987
Craig F, Fishback N, Scwartz J, Powers C: Occult metastatic mesothelioma – Diagnosis by fine needle aspiration. A case report. Am J Clin Pathol 97: 493-497, 1992
Dutt P, Baxter J, O’Malley F, et al: Distant cutaneous metastasis of pleural malignant mesothelioma. J Cutan Pathol 19: 490- 495, 1992
Edstrom L, Dawson P, Kohler J, DeMester T: Malignant mesothelioma. A metastasis to the face. J Surg Oncol 14: 251- 254, 1980
Garcia-Reija M, Matilla J, DePaz A, et al: Unusual metastasis to the mandibular alveolus of a malignant pleural mesothelioma. Otolaryngol Head Neck Surg 126: 435-437, 2002
Hillerdal G: Malignant mesothelioma 1982: Review of 4710 published cases. Br J Dis Chest 77: 321-343, 1983
Kaye J, Wang A: Malignant mesothelioma with brain metastases. Am J Med 80: 95-97, 1987
Kim B, Varkey B, Choi H: Diagnosis of malignant pleural mesothelioma by axillary lymph node biopsy. Chest 91: 278- 281, 1987
Kubota K, Furuse K, Kawahara M, et al: A case of malignant pleural mesothelioma with metastasis to the orbit. Jpn J Clin Oncol 26: 469-471, 1996
Losi L, Cocchi R, Calbucci F, Eusebi V: Metastasis of pleural malignant mesothelioma to the brain and upper maxilla: description of 2 cases. Pathologica 92: 273-277, 2000
MacDonald AD, Harper A, ElAttar O: Epidemiology of primary malignant mesothelial tumors in Canada. Cancer 26: 914- 919, 1970
McEwen J, Finlayson A, Mair A: Mesothelioma in Scotland. Br Med J 4: 575-578, 1970
Moertel CG: Peritoneal mesothelioma. Gastroenterology 63: 346-350, 1972
Obers V, Leiman G, Girdwood R, Spiro F: Primary malignant pleural tumors, mesotheliomas, presenting as localized masses. Fine needle aspiration cytologic findings, clinical and radiologic features and review of the literature. Acta Cytol 32: 568-575, 1988
Prieto V, Kenet B, Varghese M: Malignant mesothelioma metastatic to the skin presenting as inflammatory carcinoma. Am J Dermatopathol 19: 261-265, 1997
Roberts G: Distant visceral metastases in pleural mesothelioma. Br J Dis Chest 70: 246-250, 1976
Sebbag G, Sugarbaker P: Peritoneal mesothelioma proposal for a staging system. Eur J Surg Oncol 27: 223-224, 2001
Sgrignoli A, Abati A, Pass H, et al: Metastatic mesothelioma presenting as a salivary gland neoplasm. Acta Cytol 42: 818- 820, 1998
Sheibani K, Esteban J, Bailey A, et al: Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol 23: 107-116, 1992
Sheibani K, Shinn S, Kezirian J, Weiss L: BerEP4 antibody as a discriminant in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. Am J Surg Pathol 15: 79-84, 1991
Sterret G, Whitaker D, Shilkin K, Walters MN: Fine needle aspiration cytology of malignant mesothelioma. Acta Cytol 31: 185-193, 1987
Sussman J, Rosai J: Lymph node metastasis as the initial manifestation of malignant mesothelioma. Report of six cases. Am J Surg Pathol 14: 819-828, 1990
Wagner J, Sleggs C, Marshad P: Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 17: 260-271, 1960
Walters K, Martinez A: Malignant fibrous mesothelioma metastatic to brain and liver. Acta Neuropathol 33: 173-177, 1975
Wanebo H, Martini N, Melamed M, et al: Pleural mesothelioma. Cancer 38: 2481-2488, 1976
Yu G, Baloch Z, Gupta P: Cytomorphology of metastatic mesothelioma in fine needle aspiration specimens. Diagn Cytopathol 20: 328-332, 1999
Zanconati F, DelConte A, Bonifacio-Gori D, Falconieri G: Metastatic pleural mesothelioma presenting with solitary involvement of the tongue: a report of a new case and review of the literature. Int J Surg Pathol 11: 51-55, 2003
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 247
EP 250
PG 4
ER
PT J
AU Kondo, T
Tanaka, Y
AF Kondo, Takeshi
Tanaka, Yoshio
TI Malignant Pilomatricoma in the Parietal Area
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE malignant pilomatricoma; pilomatrix carcinoma; basophilic cells; distant metastasis
ID malignant pilomatricoma; pilomatrix carcinoma; basophilic cells; distant metastasis
AB A 27-year-old Japanese woman presented with a 2.5-cm nodular subcutaneous lesion in the parietal area. The nodule was well demarcated and situated in the dermis and subcutis. Histologically, the tumor was diagnosed as malignant pilomatricoma. The tumor was excised, the postoperative course was uneventful, no evidence of local recurrence or distant metastasis was observed, and the patient continues to be under close follow-up. Malignant pilomatricoma, a locally aggressive counterpart of benign pilomatricoma, is also referred to as pilomatrix carcinoma. Most cases are excised as benign tumors; however, when the excision is incomplete local recurrence is likely, and distant metastases have also been reported. Histologically, the diagnosis can be challenging because no clear histologic criteria are available. Because of the rarity of malignant pilomatricoma, no welldefined standards in the surgical management of this neoplasm have been established. Moreover, since distant metastases have been described, close followup of the lesion is requisite.
C1 [Kondo, Takeshi] Kobe University Graduate School of Medicine, Department of Biomedical Informatics, Division of Molecular Pathology, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017 Kobe, Japan.
[Tanaka, Yoshio] Shinko Hospital, Department of Plastic SurgeryKobe, Japan.
RP Kondo, T (reprint author), Kobe University Graduate School of Medicine, Department of Biomedical Informatics, Division of Molecular Pathology, 650-0017 Kobe, Japan.
EM kondo@med.kobe-u.ac.jp
CR Dutta R, Boadle R, Ng T: Pilomatrix carcinoma: case report and review of literature. Pathology 33: 248-251, 2001
Elder D, Elenitsas R, Ragsdale BD: Tumors of the epidermal appendages. In: LEVER’s Histopathology of the Skin. 8th ed., Ed: Elder D), Lippincott-Raven, Philadelphia, 1997, p759
Fujiwara T, Yamamoto H, Hashiro M: Malignant pilomatricoma. Scand J Plast Reconstr Surg Hand Surg 36: 119-121, 2002
Gould E, Kurzon R, Kowalczyk AP, Saldana M:Pilomatrix carcinoma with pulmonary metastasis. Report of a case. Cancer 54: 370-372, 1984
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 251
EP 253
PG 3
ER
PT J
AU Merkli, H
Pal, E
Gati, I
AF Merkli, Hajnalka
Pal, Endre
Gati, Istvan
TI Asymmetric Calf Hypertrophy of Neurogenic Origin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE asymmetric atrophy; muscle biopsy; neuropathy; spinal muscular atrophy
ID asymmetric atrophy; muscle biopsy; neuropathy; spinal muscular atrophy
AB A 47-year-old male presented with painful swelling of the right calf. His medical history was negative, except for a herniation of disc LIV-V 5 years before. Physical examination revealed unilateral calf hypertrophy with moderate weakness of plantarflexion, mild paresis of dorsiflexion. Electromyography showed a peripheral neurogenic lesion in the right anterior tibial muscle, but normal findings were obtained from the unaffected quadriceps muscle. Histological examination of the right gastrocnemic muscle showed neurogenic changes with typical targetoid fibers, but no pathological changes were present in the quadriceps muscle. Chronic asymmetric spinal muscular atrophy is an infrequent neuromuscular disease and because of asymmetric appearance, it might be difficult to distinguish from other, acquired neurogenic muscle diseases such as radiculopathy caused by intervertebral disc herniation. Our case confirms that muscular hypertrophy can follow partial denervation in humans.
C1 [Merkli, Hajnalka] University of Pecs, Department of Neurology, Ret u. 2., H-7623 Pecs, Hungary.
[Pal, Endre] University of Pecs, Department of Neurology, Ret u. 2., H-7623 Pecs, Hungary.
[Gati, Istvan] University of Pecs, Department of Neurology, Ret u. 2., H-7623 Pecs, Hungary.
RP Pal, E (reprint author), University of Pecs, Department of Neurology, H-7623 Pecs, Hungary.
EM endre.pal@aok.pte.hu
CR Adams RD, Denny-Brown D, Pearson CM: Diseases of Muscle. A Study in Pathology. Second Edition. Harper and Row, Hagerstown, Maryland, 1962, pp. 349-353, 666-669.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2006
VL 12
IS 4
BP 254
EP 256
PG 3
ER
PT J
AU Cserni, G
Bianchi, S
Vezzosi, V
Arisio, R
Bori, R
Peterse, LJ
Sapino, A
Castellano, I
Drijkoningen, M
Kulka, J
Eusebi, V
Foschini, PM
Bellocq, JP
Marin, C
Thorstenson, S
Amendoeira, I
Reiner-Concin, A
Decker, Th
Lacerda, M
Figueiredo, P
Fejes, G
AF Cserni, Gabor
Bianchi, Simonetta
Vezzosi, Vania
Arisio, Riccardo
Bori, Rita
Peterse, L Johannes
Sapino, Anna
Castellano, Isabella
Drijkoningen, Maria
Kulka, Janina
Eusebi, Vincenzo
Foschini, P Maria
Bellocq, Jean-Pierre
Marin, Cristi
Thorstenson, Sten
Amendoeira, Isabel
Reiner-Concin, Angelika
Decker, Thomas
Lacerda, Manuela
Figueiredo, Paulo
Fejes, Gabor
TI Sentinel Lymph Node Biopsy in Staging Small (up to 15 mm) Breast Carcinomas. Results from a European Multi-institutional Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sentinel lymph node; non-sentinel lymph node; breast cancer; pT1
ID Sentinel lymph node; non-sentinel lymph node; breast cancer; pT1
AB Sentinel lymph node (SLN) biopsy has become the preferred method for the nodal staging of early breast cancer, but controversy exists regarding its universal use and consequences in small tumors. 2929 cases of breast carcinomas not larger than 15 mm and staged with SLN biopsy with or without axillary dissection were collected from the authors’ institutions. The pathology of the SLNs included multilevel hematoxylin and eosin (HE) staining. Cytokeratin immunohistochemistry (IHC) was commonly used for cases negative with HE staining. Variables influencing SLN involvement and non-SLN involvement were studied with logistic regression. Factors that influenced SLN involvement included tumor size, multifocality, grade and age. Small tumors up to 4 mm (including in situ and microinvasive carcinomas) seem to have SLN involvement in less than 10%. Non-SLN metastases were associated with tumor grade, the ratio of involved SLNs and SLN involvement type. Isolated tumor cells were not likely to be associated with further nodal load, whereas micrometastases had some subsets with low risk of non-SLN involvement and subsets with higher proportion of further nodal spread. In situ and microinvasive carcinomas have a very low risk of SLN involvement, therefore, these tumors might not need SLN biopsy for staging, and this may be the approach used for very small invasive carcinomas. If an SLN is involved, isolated tumor cells are rarely if ever associated with non-SLN metastases, and subsets of micrometastatic SLN involvement may be approached similarly. With macrometastases the risk of non-SLN involvement increases, and further axillary treatment should be generally indicated.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Bianchi, Simonetta] AOU Careggi, Department of Human Pathology and OncologyFlorence, Italy.
[Vezzosi, Vania] AOU Careggi, Department of Human Pathology and OncologyFlorence, Italy.
[Arisio, Riccardo] Sant’Anna Hospital, Department of PathologyTurin, Italy.
[Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Peterse, L Johannes] The Netherlands Cancer Institute, Department of PathologyAmsterdam, The Netherlands.
[Sapino, Anna] University of Turin, Department of Biological Science and Human OncologyTurin, Italy.
[Castellano, Isabella] University of Turin, Department of Biological Science and Human OncologyTurin, Italy.
[Drijkoningen, Maria] University Hospitals Leuven, Pathologische OntleedkundeLeuven, Belgium.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Eusebi, Vincenzo] Bellaria Hospital, Pathologic Anatomy UnitBologna, Italy.
[Foschini, P Maria] Bellaria Hospital, Pathologic Anatomy UnitBologna, Italy.
[Bellocq, Jean-Pierre] Hopital de Hautepierre, Service d’Anatomie PathologiqueStrasbourg, France.
[Marin, Cristi] Hopital de Hautepierre, Service d’Anatomie PathologiqueStrasbourg, France.
[Thorstenson, Sten] Kalmar Hospital, Department of Pathology and CytologyKalmar, Sweden.
[Amendoeira, Isabel] University of Porto, Department of Pathology and Immunology of ICBASPorto, Portugal.
[Reiner-Concin, Angelika] Donauspital, Pathologisch-Bakteriologisches InstitutVienna, Austria.
[Decker, Thomas] University of Munster, Department of PathologyMunster, Germany.
[Lacerda, Manuela] Centro Regional De Oncologia De Coimbra, Laboratorio De HistopatologicaCoimbra, Portugal.
[Figueiredo, Paulo] Centro Regional De Oncologia De Coimbra, Laboratorio De HistopatologicaCoimbra, Portugal.
[Fejes, Gabor] Bacs-Kiskun County Teaching Hospital, Department of InformaticsKecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 5
EP 14
PG 10
ER
PT J
AU Wincewicz, A
Sulkowska, M
Koda, M
Sulkowski, S
AF Wincewicz, Andrzej
Sulkowska, Mariola
Koda, Mariusz
Sulkowski, Stanislaw
TI Clinicopathological Significance and Linkage of the Distribution of HIF-1alpha and GLUT-1 in Human Primary Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIF-1α; GLUT-1; colorectal cancer; cell survival
ID HIF-1α; GLUT-1; colorectal cancer; cell survival
AB HIF-1alpha induces GLUT-1 expression, and their presence has been evaluated in colorectal cancer. However, the expressions of GLUT-1 and HIF-1alpha have not been investigated together with reference to clinicopathological characteristics in human colorectal cancer. The aim of our study was to compare the expression of HIF-1alpha and GLUT-1 with various clinicopathological features of colorectal cancer. The presence of HIF-1alpha and GLUT-1 was visualized immunohistochemically in 123 primary tumors. Membranous localization of GLUT-1 was found in multifocally necrotizing cancer samples, while pure cytoplasmic perinuclear, mostly supranuclear GLUT-1 accumulation was characteristic of cancer fields with lack of necrosis. HIF-1alpha was located in the cytoplasm and occasionally in the nuclei of cancer cells. Immunoreactivity to GLUT-1 was significantly higher in node-positive cancers compared with nodenegative ones (p=0.04), confirming our earlier results obtained on a larger number of patients. Non-mucinous adenocarcinomas expressed GLUT-1 and HIF-1alpha with significantly greater frequency than mucinous adenocarcinomas (p=0.002, p=0.0002, respectively). GLUT-1 and HIF-1alpha expression did not differ in relation to tumor stage, location, or patients’ age or gender. In contrast to that of GLUT-1, expression of HIF-1alpha correlated with grade (p=0.00003) without difference with regard to pN status. HIF-1alpha expression correlated with GLUT-1 expression in the whole patient population, as well as in all clinicopathological groups except for the pT1+pT2 group. Although the coexpression of cytoplasmic HIF-1alpha and GLUT-1 does not directly prove the dependence between HIF-1 as a nuclear transcriptional factor and GLUT-1 as its downstream protein, it is evidence of their simultaneous upregulation. The extranuclear accumulation of HIF-1alpha and GLUT-1 requires further studies to explain its significance in colorectal cancer.
C1 [Wincewicz, Andrzej] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Sulkowska, Mariola] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Koda, Mariusz] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Sulkowski, Stanislaw] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
RP Sulkowski, S (reprint author), Medical University of Bialystok, Department of General Pathomorphology, 15-269 Bialystok, Poland.
EM sulek@zeus.amb.edu.pl
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 15
EP 20
PG 6
ER
PT J
AU Kiss, J
Timar, J
Somlai, B
Gilde, K
Fejos, Zs
Gaudi, I
Ladanyi, A
AF Kiss, Judit
Timar, Jozsef
Somlai, Beata
Gilde, Katalin
Fejos, Zsuzsanna
Gaudi, Istvan
Ladanyi, Andrea
TI Association of Microvessel Density with Infiltrating Cells in Human Cutaneous Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; immunohistochemistry; lymphocytes; macrophages; microvessel density
ID angiogenesis; immunohistochemistry; lymphocytes; macrophages; microvessel density
AB Vascularization and host response to malignant tumors may have common molecular regulators, therefore, we analyzed the relationship between microvessel density (MVD) and tumor infiltrating cells in cutaneous malignant melanoma. Density of lymphocyte subpopulations, macrophages, dendritic cells and CD34+ microvessels was determined by immunohistochemistry in primary tumor samples from fifty-two patients with melanoma thicker than 1 mm. Intratumoral MVD did not show significant association with infiltration for any of these cell types. In the case of peritumoral reactive cell densities analyzed in the whole patient population, a positive correlation of MVD was found with CD3+ T cell density. This association was stronger in melanomas >4.0 mm and in visceral metastatic tumors. In these subgroups similar phenomenon was observed for CD8+ cells. We found significant correlation of MVD with CD68+ macrophage density only in the highest thickness category, and weak associations with B-cell and dendritic cell infiltration in visceral metastatic cases. MVD did not vary significantly in tumors categorized according to thickness, localization, ulceration or histological type. However, both intratumoral MVD and macrophage infiltration were significantly higher in male patients compared to females. The correlation of immune cell density with tumor vascularization and gender differences in vascularity and macrophage infiltration of melanoma deserve further attention.
C1 [Kiss, Judit] National Institute of Oncology, Department of Tumor Progression, 7-9 Rath Gy. u., H-1122 Budapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, 7-9 Rath Gy. u., H-1122 Budapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Fejos, Zsuzsanna] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Gaudi, Istvan] National Institute of Oncology, National Cancer RegistryBudapest, Hungary.
[Ladanyi, Andrea] National Institute of Oncology, Department of Tumor Progression, 7-9 Rath Gy. u., H-1122 Budapest, Hungary.
RP Ladanyi, A (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
EM ladanyi@oncol.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 21
EP 31
PG 11
ER
PT J
AU Park, HR
Park, YK
AF Park, Hye-Rim
Park, Yong-Koo
TI Differential Expression of Runx2 and Indian Hedgehog in Cartilaginous Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Runx2; Indian hedgehog; cartilaginous tumors
ID Runx2; Indian hedgehog; cartilaginous tumors
AB Runx2-Cbfa1, a Runt transcription factor, plays important roles during skeletal development. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. In addition, Indian hedgehog (Ihh) signaling molecules control the space and timing of chondrocyte differentiation. Our goal was to gain a better understanding of the molecular process underlying the development of chondrosarcoma and to investigate whether there is a biological difference among variable types of chondrosarcomas. To accomplish this we collected a series of 10 enchondromas and 57 chondrosarcomas (conventional, n = 17; mesenchymal, n = 20; clear cell, n = 20), and investigated the expression of Runx2 and Ihh in these cartilaginous tumors by immunohistochemistry. Cellular and matrix-rich areas were evaluated separately. Runx2 was expressed in 100% of conventional, mesenchymal, and clear cell chondrosarcomas, and in 30% of enchondromas. Higher levels of expression of Runx2 were found in cellular areas than in matrixrich areas. Expression levels increased with increasing histological grade in conventional chondrosarcoma, suggesting involvement in tumor progression. Ihh was expressed in 100% of conventional and clear cell chondrosarcomas, especially in matrix-rich areas. Mesenchymal chondrosarcomas revealed only focal expression of Ihh in matrix-rich areas. Small cell areas were negative. Ihh was absent or focally expressed in enchondromas. These findings demonstrate that Runx2 expression is active in variable chondrosarcomas compared to enchondromas, suggesting its importance in growth and differentiation of neoplastic cartilage. Ihh expression is considered a marker of the hypertrophic stage of differentiation in these tumor cells.
C1 [Park, Hye-Rim] Hallym University, Department of PathologyAnyang, South Korea.
[Park, Yong-Koo] Kyung Hee University, College of Medicine, Department of Pathology, #1 Hoeki-dong, Dongdaemun-ku, 130-702 Seoul, South Korea.
RP Park, YK (reprint author), Kyung Hee University, College of Medicine, Department of Pathology, 130-702 Seoul, South Korea.
EM ykpark@khmc.or.kr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 32
EP 37
PG 6
ER
PT J
AU Arslantas, A
Artan, S
Oner,
Muslumanoglu, HM
Ozdemir, M
Durmaz, R
Arslantas, D
Vural, M
Cosan, E
Atasoy, AM
AF Arslantas, Ali
Artan, Sevilhan
Oner, Ulku
Muslumanoglu, Hamza Mahmut
Ozdemir, Muhsin
Durmaz, Ramazan
Arslantas, Didem
Vural, Murat
Cosan, Erhan
Atasoy, Ant Metin
TI Genomic Alterations in Low-Grade, Anaplastic Astrocytomas and Glioblastomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE anaplastic astrocytoma; comparative genomic hybridization; genomic imbalances; glioblastoma multiforme; low-grade astrocytoma
ID anaplastic astrocytoma; comparative genomic hybridization; genomic imbalances; glioblastoma multiforme; low-grade astrocytoma
AB To extend our understanding of potential stepwise genetic alterations that may underlie tumor progression from low-grade astrocytomas to glioblastomas, histopathologic and comparative genomic hybridization analyses were performed on tumor specimens from 68 primary lesions, including 40 glioblastomas, 10 anaplastic and 18 low-grade astrocytomas. The number of aberrations per case increased towards the higher grade tumors (grade II: 1.66±1.49; grade III: 2.80±1.68; grade IV: 3.02±1.07; F=6.955, p=0.002). A gain of 7/7q was common and the most frequently seen aberration in low-grade astrocytomas, whereas loss of 10q was the most frequently seen anomaly in anaplastic astrocytomas and glioblastomas. Chromosome 7p amplification was only detected in glioblastomas. Chromosome 10/10q deletion and combination of 1p, 19q and 17p deletions were specific to high-grade astrocytic tumors. Sequences of chromosome 7 and 10 seem to have pivotal roles in the biology of human gliomas. The genomic copy deletions of chromosomes 1p and 19q might provide an alternative mechanism in the genesis of astrocytomas.
C1 [Arslantas, Ali] Medical Faculty of Osmangazi University, Department of Neurosurgery, Hasan Polatkan Bulvari No: 102/C, Ertav apt. D:9Eskisehir, Turkey.
[Artan, Sevilhan] Medical Faculty, Osmangazi University, Department of Medical GeneticsEskisehir, Turkey.
[Oner, Ulku] Eskisehir Osmangazi University, Faculty of Medicine, Department of PathologyEskisehir, Turkey.
[Muslumanoglu, Hamza Mahmut] Medical Faculty, Osmangazi University, Department of Medical GeneticsEskisehir, Turkey.
[Ozdemir, Muhsin] Medical Faculty, Osmangazi University, Department of Medical GeneticsEskisehir, Turkey.
[Durmaz, Ramazan] Medical Faculty of Osmangazi University, Department of Neurosurgery, Hasan Polatkan Bulvari No: 102/C, Ertav apt. D:9Eskisehir, Turkey.
[Arslantas, Didem] Medical Faculty, Osmangazi University, Department of Public HealthEskisehir, Turkey.
[Vural, Murat] Medical Faculty of Osmangazi University, Department of Neurosurgery, Hasan Polatkan Bulvari No: 102/C, Ertav apt. D:9Eskisehir, Turkey.
[Cosan, Erhan] Medical Faculty of Osmangazi University, Department of Neurosurgery, Hasan Polatkan Bulvari No: 102/C, Ertav apt. D:9Eskisehir, Turkey.
[Atasoy, Ant Metin] Medical Faculty of Osmangazi University, Department of Neurosurgery, Hasan Polatkan Bulvari No: 102/C, Ertav apt. D:9Eskisehir, Turkey.
RP Arslantas, A (reprint author), Medical Faculty of Osmangazi University, Department of Neurosurgery, Eskisehir, Turkey.
EM aali@ogu.edu.tr;aarslanta@ogu.edu.tr
CR Arslantas A, Artan S, Oner U, Durmaz R, Cosan E, Atasoy MA, Basaran N, Tel E: The importance of genomic copy number changes in the prognosis of glioblastoma multiforme. Neurosurg Rev 27: 58-64, 2004
Arslantas A, Artan S, Oner U, Durmaz R, Atasoy MA, Basaran N, Tel E: Detection of chromosomal imbalances in spinal meningiomas by comparative genomic hybridization. Neurol Medico- Chirur 43: 12-19, 2003
Arslantas A, Artan S, Oner U, Durmaz R, Atasoy MA, Basaran N, Tel E: Comparative genomic hybridization analysis of genomic alterations in benign, atypical and anaplastic meningiomas. Acta Neurol Bel 102: 53-62, 2002
Backlund LM, Nilsson BR, Liu L, Ichimura K, Collins VP: Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas. Br J Cancer 93: 124-130, 2005
Bigner SH, Matthews MR, Rasheed BK, Wiltshire RN, Friedman HS, Friedman AH, Stenzel TT, Dawes DM, McLendon RE, Bigner DD: Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization. Am J Pathol 155: 375-386, 1999
Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90: 1473-1479, 1998
Durmaz R, Erken S, Arslantas A, Atasoy MA, Bal C, Tel E: Management of glioblastoma multiforme: with special reference to recurrence. Clin Neurol Neurosurg 99: 117-123, 1997
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Fan X, Aalto Y, Sanko SG, Knuutila S, Klatzmann D, Castresana JS: Genetic profile, PTEN mutation and therapeutic role of PTEN in glioblastomas. Int J Oncol 21: 1141-1150, 2002
Hirose Y, Aldape KD, Chang S, Lamborn K, Berger MS, Feuerstein BG: Grade II astrocytomas are subgrouped by chromosome aberrations. Cancer Genet Cytogenet 142:1-7, 2003
Inda MM, Fan X, Munoz J, Perot C, Fauvet D, Danglot G, Palacio A, Madero P, Zazpe I, Portillo E, Tunon T, Martinez-Penuela JM, Alfaro J, Eiras J, Bernheim A, Castresana JS: Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q. Mol Carcinog 36: 6-14, 2003
Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B: Deletion of p16 and p15 genes in brain tumors. Cancer Res 54: 6353-6358, 1994
Karlbom AE, James CD, Boethius J: Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10. Hum Genet 92: 169-174, 1993
Kitange G, Misra A, Law M, Passe S, Kollmeyer TM, Maurer M, Ballman K, Feuerstein BG, Jenkins RB: Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas. Genes Chromosomes Cancer 42: 68-77, 2005
Kunwar S, Mohapatra G, Bollen A, Lamborn KR, Prados M, Feuerstein BG: Genetic subgroups of anaplastic astrocytomas correlate with patient age and survival. Cancer Res 61: 7683- 7688, 2001
Maruno M, Yoshimine T, Muhammad AK, Ninomiya H, Kato A, Hayakawa T: Chromosomal aberrations detected by comparative genomic hybridization, CGH, in human astrocytic tumors. Cancer Lett 135: 61-66, 1999
Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A: DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nat Genet 17: 32-39, 1997
Nagai H, Pineau P, Tiollais P, Buendia MA, Dejean A: Comprehensive allelotyping of human hepatocellular carcinoma. Oncogene 14: 2927-2933, 1997
Nishizaki T, Kubota H, Harada K, Harada K, Ito H, Suzuki M, Sasaki K: Clinical evidence of distinct subgroups of astrocytic tumors defined by comparative genomic hybridization. Hum Pathol 31: 608-614, 2000
Nishizaki T, Ozaki S, Harada K, Ito H, Arai H, Beppu T, Sasaki K: Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization. Genes Chromosomes Cancer 21: 340-346, 1998
Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P: Genetic pathways to glioblastoma: a population study. Cancer Res 64: 6892-6899, 2004
Ohgaki H, Schauble B, zur Hausen A, von Ammon K, Kleihues P: Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch 427:113-118, 1995
Sano T, Lin H, Chen X, Langford LA, Koul D, Bondy ML, Hess KR, Myers JN, Hong YK, Yung WK, Steck PA: Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis. Cancer Res 59: 1820-1824, 1999
Schmidt MC, Antweiler S, Urban N, Mueller W, Kuklik A, Meyer- Puttlitz B, Wiestler OD, Louis DN, Fimmers R, von Deimling A: Impact of genotype and morphology on the prognosis of glioblastoma. Neuropathol Exp Neurol 61: 321-328, 2002
Schrock E, Thiel G, Lozanova T, du Manoir S, Meffert MC, Jauch A, Speicher MR, Nurnberg P, Vogel S, Janisch W: Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses. Am J Pathol 144: 1203-1218, 1994
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 39
EP 46
PG 8
ER
PT J
AU Amirzargar, AA
Khosravi, F
Dianat, SS
Alimoghadam, K
Ghavamzadeh, F
Ansaripour, B
Moradi, B
Nikbin, B
AF Amirzargar, Ali-Akbar
Khosravi, Farideh
Dianat, S Saied
Alimoghadam, Kamran
Ghavamzadeh, Fereidoun
Ansaripour, Bita
Moradi, Batool
Nikbin, Behrooz
TI Association of HLA Class II Allele and Haplotype Frequencies with Chronic Myelogenous Leukemia and Age-at-Onset of the Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic myelogenous leukemia; genetic susceptibility; HLA-DRB; HLA-DQA1; HLA-DQB1
ID chronic myelogenous leukemia; genetic susceptibility; HLA-DRB; HLA-DQA1; HLA-DQB1
AB Chronic myelogenous leukemia (CML) is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. To clarify the association between HLA class II allele and haplotype frequencies in CML, 50 patients referred to Hematology Oncology and Bone Marrow Transplantation (BMT) center, Shariaty Hospital, Tehran, Iran, were randomly selected and compared with a group of 80 unrelated healthy blood donor subjects. HLA class II alleles were determined by PCR-SSP method. The results showed that the frequencies of DQB1*03011 (P=0.01) and DQA1*0505 (P=0.05) were higher, while that of DQB1*03032 (P=0.04) was lower in patients than in the controls. Regarding age-at-onset, the frequency of HLA-DRB1*07 (P=0.03) and -DQA1*0201 (P=0.03) alleles were higher in patients younger than 35 years. The most frequent haplotypes in our CML patients were HLA-DRB1*11/-DQB1*03011/-DQA1*0505 (P=0.01) and HLA-DRB1*04/-DQB1*0302/-DQA1*03011 (P=0.02). In conclusion, it is suggested that positive and negative association in certain HLA alleles and haplotypes exist in Iranian patients with CML.
C1 [Amirzargar, Ali-Akbar] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Khosravi, Farideh] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Dianat, S Saied] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Alimoghadam, Kamran] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow TransplantationTehran, Iran.
[Ghavamzadeh, Fereidoun] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow TransplantationTehran, Iran.
[Ansaripour, Bita] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Moradi, Batool] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Nikbin, Behrooz] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
RP Amirzargar, AA (reprint author), Tehran University of Medical Sciences, Faculty of Medicine, Department of Immunology, Tehran, Iran.
EM Amirzargar_ali@yahoo.com
CR Amirzargar A, Mytilineos J, Farjadian S, et al: Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Hum Immunol 62:1234-1238, 2001
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ten Bosch GJA, Toornvliet AC, Friede T, et al: Recognition of peptides corresponding to the joining region of p210BCR-ABL protein by human T cells. Leukemia 9: 1344-1348, 1995
Caruso C, Lo Campo P, Botindari C, Modica MA: HLA antigens in Sicilian patients affected by chronic myelogenous leukaemia. J Immunogenet 14: 295-299, 1987
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Mundhada S, Luthra R, Cano P: Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22,, q34;q11). BMC Cancer 4: 25, 2004
Oguz FS, Kalayoglu S, Diler AS, et al: HLA system affects the age-at-onset in chronic myeloid leukemia. Am J Hematol 73: 256-262, 2003
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Yotnda P, Firat H, Garcia-Pons F, et al: Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest 101: 2290-2296, 1998
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 47
EP 51
PG 5
ER
PT J
AU Magyari, L
Bene, J
Komlosi, K
Talian, G
Farago, B
Csongei, V
Jaromi, L
Safrany, E
Sipeky, Cs
Lakner, L
Varga, M
Gasztonyi, B
Melegh, B
AF Magyari, Lili
Bene, Judit
Komlosi, Katalin
Talian, Gabor
Farago, Bernadett
Csongei, Veronika
Jaromi, Luca
Safrany, Eniko
Sipeky, Csilla
Lakner, Lilla
Varga, Marta
Gasztonyi, Beata
Melegh, Bela
TI Prevalence of SLC22A4 1672T and SLC22A5 -207C Combination Defined TC Haplotype in Hungarian Ulcerative Colitis Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ulcerative colitis; OCTN1; OCTN2; SLC22A4; SLC22A5; TC haplotype
ID ulcerative colitis; OCTN1; OCTN2; SLC22A4; SLC22A5; TC haplotype
AB Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. The aim of this study was to verify the prevalence rate of the haplotype called TC, determined by combination of two functional alleles of OCTN cation transporter genes (SLC22A4 1672T and SLC22A5 -207C combination variants) in ulcerative colitis patients and unrelated healthy controls. The ''TC haplotype” has recently been suggested to confer risk for UC. A total of 121 unrelated Hungarian subjects with UC and 110 matched controls were genotyped for the two single nucleotide polymorphisms. The genotypes were determined by using PCR/RFLP assay and direct sequencing. The SLC22A4 1672T allele frequency was 46.7% in the patients with UC and 46.4% in the controls, whereas the SLC22A5 -207C allele occurred in 48.8% of the patients and 51.4% of the controls. The prevalence of the TC haplotype was 19% in the patient group and 22.7% in controls. Since there was no accumulation of the TC haplotype in the patient group, our observation suggests that carrying the TC haplotype is not associated with a higher risk for UC in the Hungarian population.
C1 [Magyari, Lili] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Bene, Judit] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Komlosi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Talian, Gabor] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Farago, Bernadett] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Csongei, Veronika] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Jaromi, Luca] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Safrany, Eniko] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Sipeky, Csilla] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
[Lakner, Lilla] Markusovszky Hospital, Department of Medicine and GastroenterologySzombathely, Hungary.
[Varga, Marta] Rethy Pal Hospital, 3rd Department of Medicine and GastroenterologyBekescsaba, Hungary.
[Gasztonyi, Beata] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti ut 12, H-7624 Pecs, Hungary.
CR Babusukumar U, Wang T, McGuire E, et al: Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease. Am J Gastroenterol 101:1354-1361, 2006
Bene J, Komlosi K, Havasi V, et al: Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis. World J Gastroenterol 12:110-113, 2006
Bene J, Magyari L, Talian G, et al: Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn's disease. World J Gastroenterol 12:5550- 5553, 2006
Bonen DK, Cho JH: The genetics of inflammatory bowel disease. Gastroenterology 124:521-536, 2003
Danese S, Fiocchi C: Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol 12:4807-4812, 2006
Eaden JA, Abrams KR, Mayberry JF: The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526-535, 2001
Gazouli M, Mantzaris G, Archimandritis AJ, et al: Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease. World J Gastroenterol 11:7525-7530, 2005
Giallourakis C, Stoll M, Miller K, et al: IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Am J Hum Genet 73:205-211, 2003
Jantchou P, Monnet E, Carbonnel F: [Environmental risk factors in Crohn's disease and ulcerative colitis, excluding tobacco and appendicectomy)], in French). Gastroenterol Clin Biol 30:859-867, 2006
Leung E, Hong J, Fraser AG, et al: Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort. Immunol Cell Biol 84:233-236, 2006
Machida H, Tsukamoto K, Wen CY, et al: Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese. World J Gastroenterol 11:4188-4193, 2005
Mahid SS, Minor KS, Soto RE, et al: Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc 81:1462- 1471, 2006
Mahida YR, Rolfe VE: Host-bacterial interactions in inflammatory bowel disease. Clin Sci, Lond, 107:331-341, 2004
Martinez A, Del Carmen MM, Mendoza JL, et al: Association of the organic cation transporter OCTN genes with Crohn's disease in the Spanish population. Eur J Hum Genet 14:222- 226, 2006
Medici V, Mascheretti S, Croucher PJ, et al: Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations. Eur J Hum Genet 14:459-468, 2006
Newman B, Gu X, Wintle R, et al: A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease. Gastroenterology 128:260-269, 2005
Noble CL, Nimmo ER, Drummond H, et al: The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease. Gastroenterology 129:1854- 1864, 2005
Palmieri O, Latiano A, Valvano R, et al: Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 23:497-506, 2006
Peltekova VD, Wintle RF, Rubin LA, et al: Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36:471-475, 2004
Pena AS: Contribution of genetics to a new vision in the understanding of inflammatory bowel disease. World J Gastroenterol 12:4784-4787, 2006
Russell RK, Drummond HE, Nimmo ER, et al: Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut 55:1114-1123, 2006
Satsangi J, Jewell D, Parkes M, et al: Genetics of inflammatory bowel disease. A personal view on progress and prospects. Dig Dis 16:370-374, 1998
Silverberg MS: OCTNs: will the real IBD5 gene please stand up? World J Gastroenterol 12:3678-3681, 2006
Siminovitch KA: Advances in the molecular dissection of inflammatory bowel disease. Semin Immunol 18:244-253, 2006
Taylor KD, Yang H, Rotter JI: Inflammatory bowel disease. II. Gene mapping. Mol Genet Metab 74:22-44, 2001
Torkvist L, Noble CL, Lordal M, et al: The contribution of OCTN1/2 variants within the IBD5 locus to Crohn's disease in the Swedish population. Gastroenterology 128:A449, 2005
Torok HP, Glas J, Tonenchi L, et al: Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Gut 54:1421-1427, 2005
Tosa M, Negoro K, Kinouchi Y, et al: Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease. Scand J Gastroenterol 41:48-53, 2006
Urcelay E, Mendoza JL, Martinez A, et al: IBD5 polymorphisms in inflammatory bowel disease: association with response to infliximab. World J Gastroenterol 11:1187-1192, 2005
Vermeire S, Pierik M, Hlavaty T, et al: Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD. Gastroenterology 129:1845-1853, 2005
Waller S, Tremelling M, Bredin F, et al: Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Gut 55:809-814, 2006
Yang H, Taylor KD, Rotter JI: Inflammatory bowel disease. I. Genetic epidemiology. Mol Genet Metab 74:1-21, 2001
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 53
EP 56
PG 4
ER
PT J
AU Renyi, I
Bardi, E
Udvardi, E
Kovacs, G
Bartyik, K
Kajtar, P
Masat, P
Nagy, K
Galantai, I
Kiss, Cs
AF Renyi, Imre
Bardi, Edit
Udvardi, Erzsebet
Kovacs, Gabor
Bartyik, Katalin
Kajtar, Pal
Masat, Peter
Nagy, Kalman
Galantai, Ilona
Kiss, Csongor
TI Prevention and Treatment of Hyperuricemia with Rasburicase in Children with Leukemia and Non-Hodgkin’s Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE rasburicase; uric acid; tumor lysis syndrome; leukemia; lymphoma
ID rasburicase; uric acid; tumor lysis syndrome; leukemia; lymphoma
AB To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin’s lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 micromol/L to 58 micromol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.
C1 [Renyi, Imre] Semmelweis University, 1st Department of PediatricsBudapest, Hungary.
[Bardi, Edit] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei Circle, H-4012 Debrecen, Hungary.
[Udvardi, Erzsebet] Sanofi-Synthelabo Co.Budapest, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Bartyik, Katalin] University of Szeged, Department of PediatricsSzeged, Hungary.
[Kajtar, Pal] University of Pecs, Department of PediatricsPecs, Hungary.
[Masat, Peter] Markusovszky Vas Country Hospital, Department of PediatricsSzombathely, Hungary.
[Nagy, Kalman] BAZ Megyei Korhaz, GyermekosztalyMiskolc, Hungary.
[Galantai, Ilona] Madarasz Street Pediatric HospitalBudapest, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei Circle, H-4012 Debrecen, Hungary.
RP Bardi, E (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4012 Debrecen, Hungary.
EM editbardi@hotmail.com
CR Goldman SC, Holcenberg JS, Finkleinstein JZ, et al: A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood 97: 2998-3003, 2001
Pui CH, Relling MV, Lascombes F, et al: Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia 11: 1813-1816, 1997
Pui CH, Mahmoud HH, Wiley JM, et al: Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma. J Clin Oncol 19: 697- 704, 2001
Bosly A, Sonet A, Pinkerton CR, et al: Rasburicase, recombinant urate oxidase, for the management hyperuricemia in patients with cancer: report of an international compassionate use study. Cancer 98: 1048-1054, 2003
Pession A, Barbieri E: Treatment and prevention of tumor lysis syndrome in children. Experience of Associazione Italiana Ematologia Oncologia Pediatrica. Contrib Nephrol 147:80-92, 2005
Schrappe M, Reiter A, Zimmermann M, et al: Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995, Berlin-Frankfurt- Munster. Leukemia 14: 2205-2222, 2000
Reiter A, Schrappe M, Parwaresch R, et al: Non-Hodgkin’s lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage – a report of the Berlin-Frankfurt-Munster Group. Clin Oncol 113: 359-372, 1995
Masera G, Jankovic M, Zurlo MG, et al: Urate-oxidase prophylaxis of uric acid-induced renal damage in childhood leukemia. J Pediatr 7: 202-204, 1985
Cohen LF, Balow JE, Magrath IT, et al: Acute tumor lysis syndrome: A review of 37 patients with Burkitt lymphoma. Am J Med 68: 486-491, 1980
Liu CY, Sims-McCallum RP, Schiffer CA: A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy. Leuk Res 29: 463-465, 2005
Annemans L, Moeremans K, Lamotte M, et al: Pan-European multicentre economic evaluation of recombinant urate oxidase, Rasburicase, in prevention and treatment of hyperuricemia and tumor lysis syndrome in haematological cancer patients. Support Care Cancer 11: 249-257, 2003
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 57
EP 62
PG 6
ER
PT J
AU Vegso, Gy
Toth, M
Hidvegi, M
Toronyi,
Langer, MR
Dinya, E
Toth, A
Perner, F
Jaray, J
AF Vegso, Gyula
Toth, Maria
Hidvegi, Marta
Toronyi, Eva
Langer, M Robert
Dinya, Elek
Toth, Andras
Perner, Ferenc
Jaray, Jeno
TI Malignancies after Renal Transplantation during 33 Years at a Single Center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunosuppression; kidney transplantation; posttransplant malignancies; tumor risk; waiting list
ID immunosuppression; kidney transplantation; posttransplant malignancies; tumor risk; waiting list
AB This study provides an analysis of incidence and characteristics of malignant tumors of 2535 patients who underwent renal transplantation between 1973 and 2007 at the Transplantation Center in Budapest. One hundred ninety-three malignant diseases were found in 188 patients (7.6%). The incidence of thyroid-, renal- hepatic-, skin- and gastric cancers as well as of Kaposi sarcoma and lymphomas increased in our transplant patient cohort compared to the figures of the general population based on the data of our Cancer Registry. On the other hand, colorectal-, oralprostate and lung cancers were underrepresented in our patient cohort. The mean time of diagnosis of malignancies following kidney transplantation was 58.5±44.8 months. One fifth of the tumors were detected within the first year. Patients with malignancies were distributed into four groups based on the immunosuppressive regimen: group I (8.5%), azathioprine + prednisone; group II (59.0%), cyclosporine + prednisone; group III (26.6%), cyclosporine + mycophenolate mofetil + prednisone; group IV (5.9%), tacrolimus + mycophenolate mofetil + prednisone. The mean age of patients was 47.3, 53.5, 55.5 and 58.1 years in group I, II, III and IV, respectively. Oncologic and immunosuppressive therapy was decided individually. Immunosuppression was switched to rapamycin-containing regimens in 63 cases. We lost 92 patients (48.9%) with a mean survival time of 25.8±39.4 months. Cumulative 1- and 5-year survivals were 69.5% and 52%, respectively. The increasing number of cancers seen early after transplantation and the increased risk of developing a cancer due to the older age of recipients draw attention to the importance of regular oncologic screening in patients on the waiting list and after transplantation.
C1 [Vegso, Gyula] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Toth, Maria] EGIS Pharmaceuticals PLC, Medical DepartmentBudapest, Hungary.
[Hidvegi, Marta] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Toronyi, Eva] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Langer, M Robert] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Dinya, Elek] EGIS Pharmaceuticals PLC, Medical DepartmentBudapest, Hungary.
[Toth, Andras] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Jaray, Jeno] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
RP Vegso, Gy (reprint author), Semmelweis University, Department of Transplantation and Surgery, H-1082 Budapest, Hungary.
EM vegso@trans.sote.hu
CR Buell JF, Gross TG, Woodle ES: Malignancy after transplantation. Transplantation 80: S254-264, 2005
Kasiske BL, Snyder JJ, Gilbertson DT, Wang C: Cancer after kidney transplantation in the United States. Am J Transplant 4: 905-913, 2004
Adami J, Gabel H, Lindelof B, Ekstrom K, Rydh B, Glimelius B, Ekbom A, Adami HO, Granath F: Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 89: 1221-1227, 2003
Montagnino G, Lorca E, Tarantino A, Bencini P, Aroldi A, Cesana B, Braga M, Lonati F, Ponticelli C: Cancer incidence in 854 kidney transplant recipients from a single institution: comparison with normal population and with patients under dialytic treatment. Clin Transpl 10: 461-469, 1996
Lutz J, Heemann U: Tumors after kidney transplantation. Curr Opin Urol 13: 105-109, 2003
Penn I: Cancers in renal transplant recipients. Adv Ren Replace Ther 7: 147-156, 2000
Penn I: Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl 12: 147-158, 1998
Kauffman HM, Cherikh WS, McBride MA, Cheng Y, Hanto DW: Post-transplant de novo malignancies in renal transplant recipients: the past and present. Transpl Int 19: 607-620, 2006
Desoize B: Immunosuppressive agents are also carcinogens. Crit Rev Oncol Hematol 56: 1-4, 2005
Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K: Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 80: 1233-1243, 2005
Opelz G, Dohler B: Lymphomas after solid organ transplantation: A collaborative transplant study report. Am J Transplant 4: 222-230, 2004
Taylor AL, Marcus R, Bradley JA: Post-transplant lymphoproliferative disorders, PTLD, after solid organ transplantation. Crit Rev Oncol Hematol 56: 155-167, 2005
Mathew T, Kreis H, Friend P: Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transpl 18: 446-449, 2004
Otto S, Kasler M: Trends in cancer mortality and morbidity in Hungarian and international statistics. Characteristics and potential outcome of public health screening programmes., In Hungarian, Hungarian Oncology 49:99-107, 2005
Penn I: Transmission of cancer from organ donors. Ann Transplant 2: 7-12, 1997
Kinlen LJ, Eastwood JB, Kerr DN, Moorhead JF, Oliver DO, Robinson BH, de Wardener HE, Wing AJ: Cancer in patients receiving dialysis. Br Med J 280: 1401-1403, 1980
Fischereder M, Jauch KW: Prevalence of cancer history prior to renal transplantation. Transpl Int 18: 779-784, 2005
Kahan BD, Knight R, Schoenberg L, Pobielski J, Kerman RH, Mahalati K, Yakupoglu Y, Aki FT, Katz S, Van Buren CT: Ten years of sirolimus therapy for human renal transplantation: the University of Texas at Houston experience. Transplant Proc 35: 25S-34S, 2003
Yakupoglu YK, Buell JF, Woodle S, Kahan BD: Individualization of immunosuppressive therapy. III. Sirolimus associated with a reduced incidence of malignancy. Transplant Proc 38: 358-361, 2006
Taylor AL, Watson CJ, Bradley JA: Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 56: 23-46, 2005
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 63
EP 69
PG 7
ER
PT J
AU Atmaca, FA
Akbulut, Z
Demirci, A
Belenli, O
Alici, S
Balbay, MD
AF Atmaca, Fuat Ali
Akbulut, Ziya
Demirci, Alparslan
Belenli, Olcay
Alici, Suleyman
Balbay, M Derya
TI Multiple Subcutaneous Nodular Metastases from Transitional Cell Carcinoma of the Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE bladder cancer; skin metastasis; transitional cell carcinoma
ID bladder cancer; skin metastasis; transitional cell carcinoma
AB Skin metastasis from transitional cell carcinoma (TCC) of the bladder is rare. In this report an uncommon metastasis of TCC of the bladder is presented.
C1 [Atmaca, Fuat Ali] Ankara Ataturk Training and Research Hospital, 1st Urology Clinic, 475. sokak 20/20 Cukurambar, 06520 Ankara, Turkey.
[Akbulut, Ziya] Ankara Ataturk Training and Research Hospital, 1st Urology Clinic, 475. sokak 20/20 Cukurambar, 06520 Ankara, Turkey.
[Demirci, Alparslan] Ankara Ataturk Training and Research Hospital, 1st Urology Clinic, 475. sokak 20/20 Cukurambar, 06520 Ankara, Turkey.
[Belenli, Olcay] Ankara Ataturk Training and Research Hospital, 1st Pathology ClinicAnkara, Turkey.
[Alici, Suleyman] Ankara Ataturk Training and Research Hospital, Medical Oncology ClinicAnkara, Turkey.
[Balbay, M Derya] Ankara Ataturk Training and Research Hospital, 1st Urology Clinic, 475. sokak 20/20 Cukurambar, 06520 Ankara, Turkey.
RP Atmaca, FA (reprint author), Ankara Ataturk Training and Research Hospital, 1st Urology Clinic, 06520 Ankara, Turkey.
EM alifuatatmaca@yahoo.com
CR Akman Y, Cam K, Kavak A, Alper M: Extensive cutaneous metastasis of transitional cell carcinoma of the bladder. Int J Urol 10:103-104, 2003
Brownstein MH, Helwig EB: Spread of tumors to the skin. Arch Dermatol 107:80-86, 1973
Freeman JR, Esrig DE, Stein JP, Simoneau AR, Skinner EC, Chen SC, Groshen S, Lieskovsky G, Boyd SD, Skinner DGl: Radical cystectomy for high risk patients with superficial bladder cancer in the era of orthotopic urinary reconstruction. Cancer 76: 833-839, 1995
Fujita K, Sakamoto Y, Fujime M, Kitagawa R: Two cases of inflammatory skin metastasis from transitional cell carcinoma of the urinary bladder. Urol Int 53:114-116, 1994
Kumar PV, Salimi B, Musallaye A, Tadayyon A: Subcutaneous metastasis from transitional cell carcinoma of the bladder diagnosed by fine needle aspiration biopsy. Acta Cytol 44: 657- 660, 2000
Mueller TJ, Wu H, Greenberg RE, Hudes G, Topham N, Lessin SR, Uzzo RG: Cutaneous metastases from genitourinary malignancies. Urology 63: 1021-1026, 2004
Rebelakos A, Manthopoulos A, Hadjissotiriou GG: Unusual metastasis of bladder cancer. Br J Urol 64: 198, 1989
Rosen T: Cutaneous metastases. Med Clin North Am 64: 885- 900, 1980
Specter JS, Zimbler H, Deleo M, Ross JS: Skin metastases from transitional cell bladder cancer. Urology 29: 215-217, 1987
Wyldes MP, Osborn DE: Solitary cutaneous metastasis from transitional cell carcinoma of the bladder. Br J Urol 61:164, 1988
Serel TA, Ozdemir G, Yaman LS, Ozdemir H: Skin metastasis of bladder carcinoma. A case report. Mater Med Pol 26:113-114, 1994
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 70
EP 72
PG 3
ER
PT J
AU Kojima, M
Matsumoto, M
Miyazawa, Y
Shimizu, K
Itoh, H
Masawa, N
AF Kojima, Masaru
Matsumoto, Morio
Miyazawa, Yuri
Shimizu, Kazuhiko
Itoh, Hideaki
Masawa, Nobuhide
TI Follicular Lymphoma with Prominent Sclerosis (''Sclerosing Variant of Follicular Lymphoma'') Exhibiting a Mesenteric Bulky Mass Resembling Inflammatory Pseudotumor. Report of Three Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE follicular lymphoma; sclerosis; mesenterium; inflammatory pseudotumor; immunohistochemistry
ID follicular lymphoma; sclerosis; mesenterium; inflammatory pseudotumor; immunohistochemistry
AB We present three cases of follicular lymphoma (FL) exhibiting prominent sclerosis (sclerosing variant of follicular lymphoma), resembling inflammatory pseudotumor (IPT) of the lymph node, arising from mesenteric lymph node. Clinically all three cases represented bulky masses of the mesenteric lymph node. Histologically, the lesions were characterized by neoplastic lymphoid follicles separated by stromal collagenization and sclerotic process, with cellular infiltrate extending into the adjacent adipose tissue. The lesions contained variable cellular spindle cell proliferation and inflammatory infiltrate including numerous reactive T cells and histiocytes. Small capillary proliferation with vascular change was also noted. Immunohistochemical study demonstrated the myofibroblastic nature of the spindle cells. Moreover, neoplastic follicles were composed of intermediate to medium-sized lymphocytes, somewhat resembling reactive lymphoid aggregates. The overall histomorphological findings of the three lesions were similar to those of IPT of the lymph node. However, CD10, Bcl-2 and Bcl-6 immunostaining demonstrated the neoplastic nature of the lymphoid follicles and the lesions were diagnosed as FL grade 1. The present three cases indicate that the sclerosing variant of grade 1 FL should be added to the differential diagnosis from IPT of the lymph node.
C1 [Kojima, Masaru] Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 617-1, Takabayashinishi-cho, 373-8550 Ohta, Japan.
[Matsumoto, Morio] National Nishigunma Hospital, Department of HematologyShibukawa, Japan.
[Miyazawa, Yuri] National Nishigunma Hospital, Department of HematologyShibukawa, Japan.
[Shimizu, Kazuhiko] Ashikaga Red Cross Hospital, Department of Pathology and Clinical LaboratoriesAshikaga, Japan.
[Itoh, Hideaki] Maebashi Red Cross Hospital, Department of Pathology and Clinical LaboratoriesMaebashi, Japan.
[Masawa, Nobuhide] Dokkyo Medical University School of Medicine, Department of Diagnostic and Anatomic PathologyMibu, Japan.
RP Kojima, M (reprint author), Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 373-8550 Ohta, Japan.
EM mkojima@gunma-cc.jp
CR Spencer H: The pulmonary plasma cell/histiocytoma complex. Histopathology 8:903-916,1984
Coffin CM, Watterson J, Priest JR, Dehner LP: Extrapulmonary inflammatory myofibroblastic tumor, inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 19:859-872, 1995
Perrone T, De Wolf-Peeters C, Frizzera G: Inflammatory pseudotumor of lymph nodes: A distinct pattern of nodal reaction. Am J Surg Pathol 12:351-361, 1988
Facchetti F, De Wolf Peeters C, De Wever I, Frizzera G: Inflammatory pseudotumor of lymph nodes. Immunohistochemical evidence for its fibrohistiocytic nature. Am J Pathol 137: 281- 289, 1990
Davis RE, Warnke RA, Dorfman RF: Inflammatory pseudotumor of lymph nodes. Additional observations and evidence for an inflammatory etiology. Am J Surg Pathol 15:744-756, 1991
Moran CA, Suster S, Abbondanzo SL: Inflammatory pseudotumor of lymph nodes: a study of 25 cases with emphasis on morphological heterogeneity. Hum Pathol 28:332-338, 1997
Kojima M, Nakamura S, Shimizu K, Hosomura Y, Ohno Y, Itoh H, Yamane N, Yoshida K, Masawa N: Inflammatory pseudotumor of the lymph nodes. Clinicopathologic and immunohistological study of 11 Japanese cases. Int J Surg Pathol 9:207- 214, 2001
Warnke RF, Weiss LM, Chan JKC, Clearre ML, Dorfman RF: Tumor of the lymph nodes and spleen, Atlas of Tumor Pathology, 3rd series, Fascicle 14). Armed Forces Institute of Pathology, Bethesda MD, 1995, pp 63-118
Feller AC, Diebold J: Histopathology of nodal and extranodal non-Hodgkin’s lymphomas. Berlin, Springer, 2003, pp 53-66
Bennet MH: Sclerosis in non-Hodgkin’s lymphomata. Br J Cancer Suppl 31:44-52, 1975
Waldron JA, Newcomer LN, Katz ME: Sclerosing variants of follicular center cell lymphomas presenting in the retroperitoneum. Cancer 52: 712-720, 1983
Keller AR, Hochholzer L, Castleman B: Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29:670-683, 1972
Nozawa Y, Hirao M, Kamimura K, Hara Y, Abe M: Unusual case of follicular lymphoma with hyaline vascular follicles. Pathol Intern 52:794-795, 2002
McCurley TL, Gay RE, Gay S, Glick AD, Haralson MA, Collins RD: The extracellular matrix in sclerosing follicular center cell lymphomas: an immunohistochemical and ultrastructural study. Hum Pathol 17: 930-938, 1986
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2007
VL 13
IS 1
BP 74
EP 77
PG 4
ER
PT J
AU Tschaharganeh, D
Ehemann, V
Nussbaum, T
Schirmacher, P
Breuhahn, K
AF Tschaharganeh, Darjus
Ehemann, Volker
Nussbaum, Tanja
Schirmacher, Peter
Breuhahn, Kai
TI Non-specific Effects of siRNAs on Tumor Cells with Implications on Therapeutic Applicability Using RNA Interference
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE nonsense siRNA; RNA interference; RNAi; non-specific effects; functional aspects; cancer
ID nonsense siRNA; RNA interference; RNAi; non-specific effects; functional aspects; cancer
AB Elimination of protein expression using RNA interference (RNAi) significantly improves the understanding of gene function and represents a promising technique for the treatment of diseases such as cancer and neurological disorders. Accumulating evidence suggests the so-called interferon-independent non-specific gene silencing of short interfering RNA (siRNA); however, its biological and functional cellular consequences are largely unidentified. We therefore analyzed the effects of different nonsense siRNAs on characteristic bio-parameters such as cell viability, proliferation, cell cycle distribution, apoptosis, and migration of tumor cells. All analyzed cellular aspects have been observed to be significantly affected by the presence of siRNA in an interferon-independent manner: viability, mitosis, and motility were significantly diminished and programmed cell death was significantly elevated. Moreover, all cell cycle stages (G0/G1-, G2/M-, and S-phase) were moderately shifted. Together, these results support the hypothesis that siRNA, due to sequence-specific cellular consequences, modulate bio-functionality independent of the target sequence. This phenomenon affects the design of siRNA experiments for future in vitro but also for in vivo tests as well as for potential therapeutic and preventive strategies. Moreover, monitoring interferon response after transfection of siRNAs is necessary but not sufficient to exclude potential off-target effects in non-diseased cells.
C1 [Tschaharganeh, Darjus] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Ehemann, Volker] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Nussbaum, Tanja] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Schirmacher, Peter] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Breuhahn, Kai] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
RP Breuhahn, K (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
EM kai.breuhahn@med.uni-heidelberg.de
CR Sen GL, Blau HM: A brief history of RNAi: the silence of the genes. Faseb J 20:1293-1299, 2006
Watanabe T, Sudoh M, Miyagishi M, et al: Intracellular-diced dsRNA has enhanced efficacy for silencing HCV RNA and overcomes variation in the viral genotype. Gene Ther 13:883- 892, 2006
Xia X, Zhou H, Huang Y, et al: Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo. Neurobiol Dis 23:578-586, 2006
Ko K, Furukawa K, Takahashi T, et al: Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers. Oncogene 25:6924-6935, 2006
Romano PR, McCallus DE, Pachuk CJ: RNA interferencemediated prevention and therapy for hepatocellular carcinoma. Oncogene 25:3857-3865, 2006
Elbashir SM, Martinez J, Patkaniowska A, et al: Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate RNA interference is mediated by 21- and 22-nucleotide RNAs. Embo J 20:6877-6888, 2001
Kumar A, Haque J, Lacoste J, et al: Double-stranded RNAdependent protein kinase activates transcription factor NFkappa B by phosphorylating I kappa B. Proc Natl Acad Sci U S A 91:6288-6292, 1994
Reynolds A, Anderson EM, Vermeulen A, et al: Induction of the interferon response by siRNA is cell type- and duplex lengthdependent. RNA 12:988-993, 2006
Persengiev SP, Zhu X, Green MR: Nonspecific, concentrationdependent stimulation and repression of mammalian gene expression by small interfering RNAs, siRNAs). RNA 10:12- 18, 2004
Semizarov D, Frost L, Sarthy A, et al: Specificity of short interfering RNA determined through gene expression signatures. Proc Natl Acad Sci U S A 100:6347-6352, 2003
Jackson AL, Bartz SR, Schelter J, et al: Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635-637, 2003
Kern MA, Schubert D, Sahi D, et al: Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells. Hepatology 36:885-894, 2002
Ehemann V, Hashemi B, Lange A, et al: Flow cytometric DNA analysis and chromosomal aberrations in malignant glioblastomas. Cancer Lett 138:101-106, 1999
Ehemann V, Sykora J, Vera-Delgado J, et al: Flow cytometric detection of spontaneous apoptosis in human breast cancer using the TUNEL-technique. Cancer Lett 194:125-131, 2003
Nicoletti I, Migliorati G, Pagliacci MC, et al: A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271-279, 1991
Scacheri PC, Rozenblatt-Rosen O, Caplen NJ, et al: Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proc Natl Acad Sci U S A 101:1892-1897, 2004
Doench JG, Petersen CP, Sharp PA: siRNAs can function as miRNAs. Genes Dev 17:438-442, 2003
Fedorov Y, Anderson EM, Birmingham A, et al: Off-target effects by siRNA can induce toxic phenotype. RNA 12:1188-1196, 2006
Ullu E, Tschudi C, Chakraborty T: RNA interference in protozoan parasites. Cell Microbiol 6:509-519, 2004
Jackson AL, Burchard J, Schelter J, et al: Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA 12:1179-1187, 2006
Jackson AL, Burchard J, Leake D, et al: Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12:1197-1205, 2006
Schwarz DS, Hutvagner G, Haley B, et al: Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Mol Cell 10:537-548, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 84
EP 90
PG 7
ER
PT J
AU Kruger, S
Ola, V
Feller, CA
Fischer, D
Friedrich, M
AF Kruger, Stefan
Ola, Vladislava
Feller, C Alfred
Fischer, Dorothea
Friedrich, Michael
TI Expression of Cancer-Testis Antigen CT7 (MAGE-C1) in Breast Cancer: An Immunohistochemical Study with Emphasis on Prognostic Utility
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; cancer-testis antigen; CT7; MAGE-C1; prognosis; immunohistochemistry
ID breast cancer; cancer-testis antigen; CT7; MAGE-C1; prognosis; immunohistochemistry
AB High expression of the cancer-testis antigen CT7, also referred to as MAGE-C1, has been recently described in a variety of malignant tumors, including breast carcinoma. To our knowledge, no data concerning the prognostic utility of CT7 expression in breast cancer are available. In this retrospective study, we evaluated the relationship between CT7 immunoreactivity and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 124 women with invasive breast cancer. A positive CT7 status, defined as immunoreactivity in more than 50% of tumor cells, was found in 18% of cases and correlated significantly with high tumor grade (p=0.004), but with no other clinicopathological parameter. In a univariate analysis, CT7 status showed an association with RFS by trend (p=0.107; relative risk [RR]: 1.85) and a significant association with MFS (p=0.043; RR: 2.02). In a multivariate analysis, tumor grade, stage, nodal status, angioinvasion, HER2 expression as well as estrogen and progesterone receptor expression were identified as significant independent prognostic factors of RFS and/or MFS. In this respect, CT7 expression showed a weak, statistically not significant trend towards an independent prognostic relevance concerning prediction of MFS (p=0.147; RR: 1.95). Our data suggest that estimation of CT7 immunoreactivity is of limited prognostic usefulness in breast cancer. It may provide additional information concerning assessment of MFS in selected cases.
C1 [Kruger, Stefan] University of Schleswig-Holstein, Institute of Pathology, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
[Ola, Vladislava] University of Schleswig-Holstein, Institute of Pathology, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
[Feller, C Alfred] University of Schleswig-Holstein, Institute of Pathology, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
[Fischer, Dorothea] University of Schleswig-Holstein, Department of Gynecology and ObstetricsLubeck, Germany.
[Friedrich, Michael] University of Schleswig-Holstein, Department of Gynecology and ObstetricsLubeck, Germany.
RP Kruger, S (reprint author), University of Schleswig-Holstein, Institute of Pathology, D-23538 Lubeck, Germany.
EM krueger@patho.uni-luebeck.de
CR Van den Eynde BJ, van der Bruggen P: T cell defined tumor antigens. Curr Opin Immunol 9: 684-693, 1997.
Takahashi K, Shichijo S, Noguchi M, et al: Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis. Cancer Res 55: 3478-3482, 1995.
Scanlan MJ, Gure AO, Jungbluth AA, et al: Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188: 22-32, 2002.
Suri A: Cancer testis antigens – their importance in immunotherapy and in the early detection of cancer. Expert Opin Ther 6: 379-389, 2006.
Marchand M, van Baren N, Weiynants P, et al: Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer 18: 219-230, 1999.
Banchereau J, Palucka AK, Dhodapkar M, et al: Immune and clinical responses in patients with metastatic melanoma to CD34(+, progenitor-derived dentritic cell vaccine. Cancer Res 61: 6451-6458, 2001.
Coulie PG, Karanikas V, Colau D, et al: A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc Natl Acad Sci USA 98: 10290-10295, 2001.
Bettinotti MP, Panelli MC, Ruppe E, et al: Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA-Cw*0702-associated epitope MAGE-A12:170-178. Int J Cancer 105: 210-216, 2003.
Marchand M, Punt CJ, Aamdal S, et al: Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur J Cancer 39: 70- 77, 2003.
Kruit WH, van Ojik HH, Brichard VG, et al: Phase 1/2 study of subcutaneous and intradermal immunization with recombinant MAGE-3 protein in patients with detectable metastatic melanoma. Int J Cancer 117: 596-604, 2005.
van Baren N, Bonnet MC, Dreno B, et al: Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol 23: 9008-9021, 2005.
Sadanaga N, Nagashima H, Mashino K, et al: Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res 7: 2277-2284, 2001.
Russo V, Traversari C, Verrecchia A, et al: Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int J Cancer 64: 216-221, 1995.
Jungbluth AA, Chen YT, Busam KJ, et al: CT7, MAGE-C1, antigen expression in normal and neoplastic tissues. Int J Cancer 99: 839-845, 2002.
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Chitale DA, Jungbluth AA, Marshall DS, et al: Expression of cancer-testis antigens in endometrial carcinomas using a tissue microarray. Mod Pathol 18: 119-126, 2005.
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Yamanaka K, Miyake H, Hara I, et al: Expression of MAGE genes in renal cell carcinoma. Int J Mol Med 2: 57-60, 1998.
Patard JJ, Brasseur F, Gil-Diez S, et al: Expression of MAGE genes in transitional cell carcinomas of the urinary bladder. Int J Cancer 64: 60-64, 1995.
Toh Y, Yamana H, Shichijo S, et al: Expression of MAGE-1 gene by esophageal carcinomas. Jpn J Cancer Res 86: 714-717, 1995.
Nagao T, Higashitsuji H, Nonoguchi K, et al: MAGE-A4 interacts with the liver oncoprotein gankyrin and suppresses its tumorigenic activity. J Biol Chem 278: 10668-10674, 2003.
Peikert T, Specks U, Farver C, et al: Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis. Cancer Res 66: 4693-4700, 2006.
Monte M, Simonatto M, Peche LY, et al: MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci USA 103: 11160-11165, 2006.
Riker A, Cormier J, Panelli M, et al: Immune selection after antigen-specific immunotherapy of melanoma. Surgery 126: 112-120, 1999.
El-Shami K, Tirosh B, Bar-Haim E, et al: MHC class I-restricted epitope spreading in the context of tumor rejection following vaccination with a single immunodominant CTL epitope. Eur J Immunol 29: 3295-3301, 1999.
Markiewicz MA, Fallarino F, Ashikari A, et al: Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A. Int Immunol 13: 625-632, 2001.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 91
EP 96
PG 6
ER
PT J
AU Badalian, G
Barbai, T
Raso, E
Derecskei, K
Szendroi, M
Timar, J
AF Badalian, Gayane
Barbai, Tamas
Raso, Erzsebet
Derecskei, Katalin
Szendroi, Miklos
Timar, Jozsef
TI Phenotype of Bone Metastases of Non-Small Cell Lung Cancer: Epidermal Growth Factor Receptor Expression and K-RAS Mutational Status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR immunohistochemistry; K-RAS mutation; NSCLC; bone metastasis
ID EGFR immunohistochemistry; K-RAS mutation; NSCLC; bone metastasis
AB Bone metastasis is a frequent complication of lung cancer progression, however, studies on bone metastatic tissues are scanty. Here we have collected a small cohort of 11 non-small cell lung cancer cases where primary tumors and corresponding bone metastases were available for pathological analysis. We have tested two molecular markers: EGFR protein expression and K-RAS mutation at codon 12 using immunohistochemistry and RFLPPCR, respectively. We have shown that using improved protocols, EGFR protein (both the extracellular as well as the cytoplasmic domain) is readily detectable in decalcified bone tissue. We found that the EGFR expression status is highly similar in bone metastases compared to the primary tumors, although the expression levels may change. Individual comparison of corresponding primary and metastatic NSCLC tissues indicated that downregulation of EGFR was a rare event (2/11) compared to upregulation (4/11) in bone metastases. On the other hand, our data indicate that the K-RAS mutational status of the primary tumor does not predict the status of the bone metastatic tissue of NSCLC, since we have observed both emergence of mutant clones in metastases from wild-type (wt) primary tumors and loss of mutant clones in metastases from mutant primaries in addition to the maintained mutant status. Our data support that at least two progression models occur in NSCLC, the samegene as well as the clonal selection one. It is noteworthy that in NSCLC cases with wt- or mutant KRAS, downregulation of EGFR expression was a rare event although upregulation in bone metastases was observed more frequently in wt K-RAS cases.
C1 [Badalian, Gayane] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Barbai, Tamas] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Raso, Erzsebet] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Derecskei, Katalin] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Timar, Jozsef] National Institute of Oncology, Department of Tumor Progression, Rath Gyorgy u. 7-9., H-1122 Budapest, Hungary.
RP Timar, J (reprint author), National Institute of Oncology, Department of Tumor Progression, H-1122 Budapest, Hungary.
CR Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584-593, 2002
Roodman GD: Mechanisms of bone metastasis. N Engl J Med 350:1655-1664, 2004
Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I: Diversity of the gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 98:13784-13789, 2001
Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB, Hanash S: Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 8:816-824, 2002
Kopper L, Timar J: Genomics of lung cancer may change diagnosis, prognosis and therapy. Pathol Oncol Res 11:5-10, 2005
Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A, Camplese PP, Iarussi T, Mucilli F, Mezzetti A, Cuccurullo F, Sacco R, Buttitta F: EGFR mutations in non-smallcell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 23:857-865, 2005
Aviel-Ronen S, Blackhall FH, Shepherd FA, Shepherd FA, Tsao MS: K-ras mutations in non-small cell lung carcinoma: a review. Clin Lung Cancer 8:30-38, 2006
Soung YH, Lee JW, Kim SY, Seo SH, Park WS, Nam SW, Song SY, Han JH, Park CK, Lee JY, Yoo NJ, Lee SH: Mutational analysis of EGFR and K-RAS genes in lung adenocarcinomas. Virchows Arch 446:483-488, 2005
Riely GJ, Politi KA, Miller VA, Pao W: Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res 12:7232-7241, 2006
Derecskei K, Moldvay J, Bogos K, Timar J: Protocol modifications influence the result of EGF receptor immunodetection by EGFR pharmDxTM in paraffin-embedded cancer tissues. Pathol Oncol Res 12: 243-246, 2006
Molina JR, Adjei AA, Jett JR: Advances in chemotherapy of non-small cell lung cancer. Chest 130:1211-1219, 2006
Bepler G, Li X, Sharma A et al: Clinical value of tumoral RRM1 and ERCC1 expressions for treatment response and therapeutic decisions in NSCLC. In: ASCO 2006 Education Book, Ed.: M.C. Perry, ASCO, Alexandria, 2006, pp 431-435
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Petersen S, Aninat-Mayer M, Schluns K, Gellert K, Dietel M, Petersen I: Chromosomal alteration in the clonal evolution of the metastatic stage of squamous cell carcinoma of the lung. Br J Cancer 82:65-73, 2000
Takahashi K, Kohno T, Matsumoto S, Nakanishi Y, Arai Y, Yamamoto S, Fujiwara T, Tanaka N, Yokota J: Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells. Clin Cancer Res 13:111-120, 2007
Matsumoto S, Takahasi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T, Shimizu E, Yokota J: Frequent EGFR mutation in brain metastases of lung adenocarcinoma. Int J Cancer 15:1491-1494, 2006
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 99
EP 104
PG 6
ER
PT J
AU Sanada, Y
Yoshida, K
Ohara, M
Tsutani, Y
AF Sanada, Yuichi
Yoshida, Kazuhiro
Ohara, Masahiro
Tsutani, Yasuhiro
TI Expression of Orotate Phosphoribosyltransferase (OPRT) in Hepatobiliary and Pancreatic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OPRT; pancreatic carcinoma; gallbladder carcinoma; hepatocellular carcinoma; pancreatic intraepithelial neoplasia (PanIN)
ID OPRT; pancreatic carcinoma; gallbladder carcinoma; hepatocellular carcinoma; pancreatic intraepithelial neoplasia (PanIN)
AB The purpose of this study was to clarify the role of orotate phosphoribosyltransferase (OPRT) in the progression of hepatobiliary and pancreatic carcinomas. Representative sections from 8 surgically resected pancreatic carcinomas, 5 gallbladder carcinomas and 19 hepatocellular carcinomas (HCCs) were examined microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma of the pancreas (IDC) were determined. Gallbladder carcinomas and HCCs were examined histologically, and the subtypes and spread patterns were assessed. Expression of OPRT was examined immunohistochemically. A total of 75 PanINs were identified. Expression of OPRT increased as lesions progressed from early to high-grade PanINs (PanIN-1A and -1B versus PanIN-2 and -3, p=0.0004). Three (37.5%) of the 8 pancreatic IDCs were positive for OPRT. In the remaining 5 cases, OPRT was expressed only in the neoplastic ducts adjacent to PanIN-3s. In gallbladder carcinomas, mucosal neoplastic epithelium showed dense cytoplasmic expression in 4 of the 5 cases, but expression was absent in the deeply invasive lesions. Among HCCs, 15 of the 19 cases were negative for OPRT in the central area of the tumor, but 8 of the 19 cases expressed OPRT in vascularly invasive lesions. Our data suggest that OPRT is involved in early events of pancreatic and gallbladder carcinogenesis and invasion of HCC.
C1 [Sanada, Yuichi] Hiroshima University, Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, 1-2-3 Kasumi, 734-8551 Hiroshima, Minami-ku, Japan.
[Yoshida, Kazuhiro] Hiroshima University, Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, 1-2-3 Kasumi, 734-8551 Hiroshima, Minami-ku, Japan.
[Ohara, Masahiro] Hiroshima University, Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, 1-2-3 Kasumi, 734-8551 Hiroshima, Minami-ku, Japan.
[Tsutani, Yasuhiro] Hiroshima University, Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, 1-2-3 Kasumi, 734-8551 Hiroshima, Minami-ku, Japan.
RP Sanada, Y (reprint author), Hiroshima University, Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, 734-8551 Hiroshima, Japan.
EM ysanadasurg@hotmail.com
CR Sakamoto K, Sugimoto Y, Miyadera K, et al: Preparation of anti-orotate phosphoribosyltransferase antibody and its application to immunohistochemical detection in human tumor cells. Int J Mol Med 16: 245-249, 2005
Oguri T, Achiwa H, Bessho Y, et al: The role of thymidylate synthase and dihydropyrimidine dehydrogenase in resistance to 5-fluorouracil in human lung cancer cells. Lung Cancer 49: 345-351, 2005
Ishida H, Shirakawa K, Ohsawa T, et al Expression of mRNA levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and orotate phosphoribosyltransferase of colorectal cancer–relationships among mRNA expression with response to 5-FU based treatment. Gan To Kagaku Ryoho 32: 1929-1934, 2005, in Japanese)
Kamoshida S, Shiogama K, Shimomura R, et al: Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer. Oncol Rep 14: 1223-1230, 2005
Ochiai T, Sugitani M, Nishimura K, et al: Impact of orotate phosphoribosyl transferase activity as a predictor of lymph node metastasis in gastric cancer. Oncol Rep 14: 987-992, 2005
Nakano J, Huang C, Liu D, et al: Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT. Br J Cancer 95: 607- 615, 2006
Ochiai T, Nishimura K, Noguchi H, et al: Prognostic impact of orotate phosphoribosyl transferase activity in resectable colorectal cancers treated by 5-fluorouracil-based adjuvant chemotherapy. J Surg Oncol 94: 45-50, 2006
Takaori K, Kobayashi Y, Matsusue S, et al: Pancreatic intraepithelial neoplasia. Pancreas 28: 257-261, 2004
Lemoine NR, Jain S, Hughes CM, et al: K-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology 102: 230-236, 1992
Wilentz RE, Lacobuzio-Donahue CA, Argani P, et al: Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that Dpc4 inactivation occurs late in neoplastic progression. Cancer Res 60: 2002-2006, 2000
Kim GE, Bae HI, Park HU, et al: Aberrant expression of MUC5AC and MUC6 gastric mucin and Sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 123: 1052-1060, 2002
Sanada Y, Yoshida K, Ohara M, et al: Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components. Pancreas 32: 164-170, 2006
Albores-Saavedra J, Shukla D, Carrick K, Henson DE: In situ and invasive adenocarcinomas of gallbladder extending into or arising from Rokitansky-Aschoff sinuses. A clinicopathologic study of 49 cases. Am J Surg Pathol 28: 621-628, 2004
Kojiro M: Histopathology of liver cancers. Best Pract Res Clin Gastroenterol 19: 39-62, 2005
Mizutani Y, Wada H, Fukushima M, et al: Prognostic significance of orotate phosphoribosyl transferase activity in bladder carcinoma. Cancer 100: 723-731, 2004
Takamori H, Kanemitsu K, Tsuji T, et al: 5-fluorouracil intraarterial infusion combined with systemic gemcitabine for unresectable pancreatic cancer. Pancreas 30: 223-226, 2005
Alberts SR, al-Khatib H, Mahoney MR, et al: Gemcitabine, 5- fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma in North Central Cancer Treatment Group phase II trial. Cancer 103: 111-118, 2005
Obi S, Yoshida H, Toure R, et al: Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer 106: 1990-1997, 2006
Sakurai Y, Sakamoto K, Sugimoto Y, et al: Orotate phosphoribosyltransferase levels measured by a newly established enzymelinked immunosorbent assay in gastric carcinoma. Cancer Sci 97: 492-498, 2006
Dhawan P, Singh AB, Deane NG, et al: Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 115: 1765-1776, 2005
Doucas H, Garcea G, Neal CP, et al: Chemoprevention of pancreatic cancer: a review of the molecular pathways involved, and evidence for the potential for chemoprevention. Pancreatology 6: 429-439, 2006
Hidaka S, Yasutake T, Fukushima M, et al: Chromosomal imbalances associated with acquired resistance to fluoropyrimidines in human colorectal cancer cells. Eur J Cancer 39: 975-980, 2003
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 105
EP 113
PG 9
ER
PT J
AU Jakso, P
Kereskai, L
Molnar, L
Pajor, L
AF Jakso, Pal
Kereskai, Laszlo
Molnar, Lenke
Pajor, Laszlo
TI Lineage-Specific Clonality Analysis of Chronic Myeloproliferative Disorders and Myelodysplastic Syndrome by Human Androgen Receptor Assay
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic myeloproliferative disease; myelodysplasia; HUMARA
ID chronic myeloproliferative disease; myelodysplasia; HUMARA
AB In myelodysplastic syndrome (MDS) as well as chronic myeloproliferative disorders (CMPD) others than chronic myeloid leukemia the frequency of pathognomonic genetic aberrations is very low and, therefore, X chromosome inactivation (XI) assays may help in assessing the clonality. To establish specific clonality criteria on XI, human androgen receptor assay (HUMARA) was performed on sorted myeloid and lymphoid peripheral blood cells of 21 healthy females. Clonality criteria 1 and 2 conferring at least 90% specificity were set based on the ranges and differences of XI number (XIN) describing the ratio of representation of the two alleles in as well as in between reactive myeloid and lymphoid compartments. Spiking experiments indicated that the test identifies clonality reliably when no more than 40-50% reactive cells are admixed. In the CMPD and MDS cases peripheral myeloid cells were monoclonal by one of the two criteria in 71-100%, whereas lymphoid cells in 28-75%. The results of HUMARA, available in 73% of the female patients, supported the clinicopathological data in 84% as well as proved pluripotent stem cell origin in 31-75% and 21% of CMPDs and MDS, respectively.
C1 [Jakso, Pal] University of Pecs, Department of Pathology, 12. Szigeti u., H-7643 Pecs, Hungary.
[Kereskai, Laszlo] University of Pecs, Department of Pathology, 12. Szigeti u., H-7643 Pecs, Hungary.
[Molnar, Lenke] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, 12. Szigeti u., H-7643 Pecs, Hungary.
RP Pajor, L (reprint author), University of Pecs, Department of Pathology, H-7643 Pecs, Hungary.
EM titkar@pathology.pote.hu
CR Allen RC, Zoghbi HY, Moseley AB: Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51:1229-1239, 1992
Anderson JE, Gilliland DG, List AF: Myelodysplastic syndrome. Educational Materials by the American Society of Hematology, 1998
Baxter EJ, Scott LM, Campbell PJ: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054-1061, 2005
Busque L, Gilliland DG: X-inactivation analysis in the 1990s: promise and potential problems. Leukemia 12:128-135, 1998
Culligan DJ, Cachia P, Wittaker J: Clonal lymphocytes are detectable in only some cases of MDS. Br J Haematol 81:346- 352, 1992
Heaney ML, Golde DW: Myelodysplasia. N Engl J Med 340:1649-1660, 1999
Hellstrom-Lindberg E, Willmann C, Barrett AJ: Achievements in understanding and treatment of myelodysplastic syndromes. Educational Materials by the American Society of Hematology, 2000.
Jaffe ES, Harris NL, Stein H, Vardinian JW eds. World Health Organization Classification of Tumours, Pathology & Genetics, Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, 2001
James C, Ugo V, Le Couedic JP: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144-1148, 2005
Knuutila S, Teerenhovi L, Larramendy ML: Cell lineage involvement of recurrent chromosomal abnormalities in hematological neoplasms. Genes, Chromosomes Cancer 10:95-102, 1994
Kralovics R, Passamonti F, Buser AS: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779-1790, 2005
Levine RL, Wadleigh M, Cools J: Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocytemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387-397, 2005
Nilsson L, Astrand-Grundstrom I: Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level. Blood 156:2012-2021, 2000
Pajor L, Matolcsy A, Vass JA, Mehes G, Marton E, Szabo F: Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome. Leuk Res 22:13-17, 1998
Pearson TC, Messinezy M, Westwood N: A Polycythemia Vera Update: diagnosis, pathobiology, and treatment. Educational Materials by the American Society of Hematology, 2000.
Raskind WH, Steinmann L, Najfeld V: Clonal development of myeloproliferative disorders: clues to hematopoietic differentiation and multistep pathogenesis of cancer. Leukemia 12: 108- 116, 1998
Tonon L, Bergamaschi G, Dellavecchia C, Rosti V, Lucotti C, Malabarba: Unbalanced X-chromosome inactivation in haematopoietic cells from normal women. Br J Haematol 102:996-1003, 1998
Zhao R, Xing S, Li Z: Identification of an acquired JAK2 mutation in Polycythemia vera. J Biol Chem 280:22788-22792, 2005
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 114
EP 122
PG 9
ER
PT J
AU Sharma, S
Sharma, ChM
Johnson, HM
Lou, M
Thakar, A
Sarkar, Ch
AF Sharma, Suash
Sharma, Chand Mehar
Johnson, H Maribeth
Lou, Mimi
Thakar, Alok
Sarkar, Chitra
TI Esthesioneuroblastoma - a Clinicopathologic Study and Role of DNA Topoisomerase Alpha
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE esthesioneuroblastoma; topoisomerase alpha
ID esthesioneuroblastoma; topoisomerase alpha
AB Esthesioneuroblastoma (ENB) differs from adrenal neuroblastomas in its histopathologic and biologic characteristics. Hyams grading and Kadish staging have shown correlation with survival. Scant data are available on proliferation indices and prognosis. We retrospectively reviewed the clinicopathologic characteristics of ENB. Both Kadish and UCLA staging systems were used. Hyams grading was simplified into low and high grade. DNA topoisomerase II alpha labeling index (T2alpha LI) was obtained in 8 cases using immunohistochemistry. Of the 19 cases studied, 14 were males and 5 females. Age range was 2 to 62 years (average 27 years). The mass primarily involved the nose in 12 (63%) and paranasal sinuses in 7 cases (37%). Patients presented with nose block in 19 (100%), epistaxis in 10 (53%), proptosis in 9 (47%) and loss of vision in 6 cases (32%). Bony involvement was seen in 7 cases (37%), and intracranial spread in one case (5%). Thirteen (68%) were low-grade tumors and 6 were (32%) high-grade. There was no statistically significant difference between the low- and high-grade ENB in age (years) (p=0.2882), duration of symptoms (months) (p=0.5636), and either in the Kadish (p=0.5456) or the UCLA staging system (p=0.7771). The difference in DNA topoisomerase alpha labeling index between the low- and highgrade ENB (medians: 10.4 and 22.3, respectively) was not statistically significant (p=0.0714), but it was suggestive of a positive association. The results of this study should be interpreted with caution, because of the limited sample size. Three cases recurred locally, one each stage A, B and C, but all low-grade. This preliminary study suggests the need to combine a simplified histologic grading with accurate staging in a reasonable attempt to assess local progression in esthesioneuroblastoma. Larger studies may clarify the role of T2alpha LI in improving histologic grading.
C1 [Sharma, Suash] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Johnson, H Maribeth] Medical College of Georgia, Biostatistics Consulting CenterAugusta, GA, USA.
[Lou, Mimi] Medical College of Georgia, Biostatistics Consulting CenterAugusta, GA, USA.
[Thakar, Alok] All India Institute of Medical Sciences, Department of OtolaryngologyNew Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Sarkar, Ch (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM drchitasarkar@yahoo.com
CR Argani P, Perez-Ordonez B, Xiao H, Cariana SM, Huvos AG, Ladanyi M: Olfactory neuroblastoma is not related to the Ewing’s family of tumors: absence of EWS/FLI1 gene fusion and MIC2 expression. Am J Surg Pathol 22: 391-398, 1998
Bockmuhl U, You X, Pacyna-Gengelbach M, Arps H, Draf W, Petersen I: CGH pattern of esthesioneuroblastoma and their metastases. Brain Pathol 14: 158-163, 2004
Broich G, Pagliari A, Ottaviani F: Esthesioneuroblastoma: a general review of the cases published since the discovery of the tumor in 1924. Anticancer Res 17: 2683-2706, 1996
Constantinidis J, Steinhart H, Koch M, Buchfelder M, Schaenzer A, Weidenbacher M, Iro H: Olfactory neuroblastoma: The University of Erlangen-Nuremberg experience 1975-2000. Otolaryngol Head Neck Surg 130:567-574, 2004
Dulguerov P, Allal AS, Calacaterra TC: Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2: 683-690, 2001
Dulguerov P, Calcaterra T: Esthesioneuroblastoma: The UCLA experience 1970-1990. Laryngoscope 102: 843-849, 1992
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 123
EP 129
PG 7
ER
PT J
AU Croce, VM
Isla-Larrain, M
Rabassa, EM
Demichelis, S
Colussi, GA
Crespo, M
Lacunza, E
Segal-Eiras, A
AF Croce, V Maria
Isla-Larrain, Marina
Rabassa, E Martin
Demichelis, Sandra
Colussi, G Andrea
Crespo, Marina
Lacunza, Ezequiel
Segal-Eiras, Amada
TI Lewis x is Highly Expressed in Normal Tissues: a Comparative Immunohistochemical Study and Literature Revision
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE carbohydrate epitopes; mucins; normal epithelia; immunohistochemistry
ID carbohydrate epitopes; mucins; normal epithelia; immunohistochemistry
AB An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.
C1 [Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Isla-Larrain, Marina] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Rabassa, E Martin] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Demichelis, Sandra] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Colussi, G Andrea] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Crespo, Marina] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Lacunza, Ezequiel] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), Calle 60 y 120La Plata, Argentina.
RP Segal-Eiras, A (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM as-eiras@netverk.com.ar
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 130
EP 138
PG 9
ER
PT J
AU Baintner, K
Bodnar, Zs
Kiss, P
Kiss, LA
Lukats,
AF Baintner, Karoly
Bodnar, Zsofia
Kiss, Peter
Kiss, L Anna
Lukats, Akos
TI Effect of Intraperitoneally Administered Plant Lectins on Leukocyte Diapedesis and Visceral Organ Weight in Rats and Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lectin; ConA; WGA; PHA; neutrophil; diapedesis; mesothelial; CINC
ID lectin; ConA; WGA; PHA; neutrophil; diapedesis; mesothelial; CINC
AB The effects of intraperitoneally administered plant lectins were examined in rats and mice. Intraperitoneally injected ConA transiently decreased the leukocyte count in the peritoneal cavity, due to the agglutination and attachment of cells to the peritoneal lining. Subsequently the total cell count was increased for hours, exceeding initial values. Peritoneal fluid aspartate transaminase (AST) concentration showed little change during the accumulation of ascitic fluid. The most marked histological alterations were found when wheat germ lectin was injected ip. (WGA, 10 mg/kg, 6 h). Neutrophil granulocytes migrated across the wall of both arterioles and venules, but the response was highly variable among adjacent vessels. The wall of the arterioles may have impeded the migration of neutrophil granulocytes, resulting in their accumulation in the muscular layer. Granulocyte accumulation was also observed in patches under the mesothelium and in other sites of the interstitium. Marked dilatation and thrombosis of a few venules were also observed. Kidney bean lectin (PHA) induced similar but less pronounced changes. The neutrophil diapedesis suggests the release of mediator(s) from mesothelial cells and/or peritoneal white cells. The cytokine-induced neutrophil chemoattractant CINC-1, injected as control, resulted in the diapedesis of predominantly mononuclear cells in the omentum within 40 minutes. In rats ip. injected ConA increased the wet weight of spleen and liver within 6 and 10 h, respectively, but kidney weight did not change. Intravascular clumping of red blood cells, thrombosis and organ weight changes also suggest the absorption of ConA into the circulation. The experiments show that plant lectins, used as models of bacterial lectins, can reproduce some aspects of peritonitis.
C1 [Baintner, Karoly] Faculty of Animal Science, University of Kaposvar, Department of Physiology, H-7401 Kaposvar, Hungary.
[Bodnar, Zsofia] Faculty of Animal Science, University of Kaposvar, Department of Physiology, H-7401 Kaposvar, Hungary.
[Kiss, Peter] University of Agriculture, Department of Agricultural ChemistryGodollo, Hungary.
[Kiss, L Anna] Faculty of Medicine, Semmelweis University, Institute of Human Morphology and Developmental BiologyBudapest, Hungary.
[Lukats, Akos] Faculty of Medicine, Semmelweis University, Institute of Human Morphology and Developmental BiologyBudapest, Hungary.
RP Baintner, K (reprint author), Faculty of Animal Science, University of Kaposvar, Department of Physiology, H-7401 Kaposvar, Hungary.
EM baintner@mail.atk.u-kaposvar.hu
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Alencar NMN, Assreuy AMS, Alencar VBM, Melo SC, Ramos MV, Cavada BS, Cunha FQ, Ribeiro RA: The galactose-binding lectin from Vatairea macrocarpa seeds induces in vivo neutrophil migration by indirect mechanism. Int J Biochem Cell Biol 35: 1674-1681, 2003
Vretblad P: Purification of lectins by biospecific affinity chromatography. Biochim Biophys Acta 434: 169-176, 1976
Pusztai A, Watt WB, Stewart JC: A comprehensive scheme for the isolation of trypsin inhibitors and the agglutinin from soybean seeds. J Agr Food Chem 39: 862-866, 1991
Bardocz S, Grant G, Pusztai A, Franklin MF, de Carvalho A: The effect of phytohaemagglutinin at different dietary concentrations on the growth, body composition and plasma insulin of the rat. Br J Nutr 76: 613-626, 1996
Smirnova IV, Khaspekova SC, Ignatov VV, Mazurov AV: Interaction of wheat germ agglutinin and concanavalin A with platelets. Stimulation of platelet functional reactions and binding with membrane glycoproteins. Biokhimija 63: 710-718, 1998
Nasreen N, Mohammed KA, Hardwick J, van Horn RD, Sanders KL, Doerschuk CM, Hott JW, Antony VB: Polar production of interleukin-8 by mesothelial cells promotes the transmesothelial migration of neutrophils: role of intercellular adhesion molecule-1. J Infect Dis 183: 1638-1645, 2001
Meager A: Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine Growth Factor Rev 10: 27-39, 1999
Ebnet K, Kaldjian EP, Anderson AO, Shaw S: Orchestrated information transfer underlying leukocyte endothelial interactions. Annu Rev Immunol 14: 155-177, 1996
McEver RP: Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 14: 581-586, 2002
Knolle PA, Gerken G, Loser E, Dienes HP, Gantner F, Tiegs G, Meyer zum Buschenfelde KH, Lohse AW: Role of sinusoidal endothelial cells of the liver in concanavalin A-induced hepatic injury in mice. Hepatology 24: 824-829, 1996
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 139
EP 143
PG 5
ER
PT J
AU Kavantzas, N
Paraskevakou, H
Tseleni-Balafouta, S
Aroni, K
Athanassiades, P
Agrogiannis, G
Patsouris, E
AF Kavantzas, Nikolaos
Paraskevakou, Helen
Tseleni-Balafouta, Sofia
Aroni, Kyriaki
Athanassiades, Pauline
Agrogiannis, George
Patsouris, Efstratios
TI Association between Microvessel Density and Histologic Grade in Renal Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE renal carcinoma; microvascular density
ID renal carcinoma; microvascular density
AB Angiogenesis seems to contribute to tumor growth and the development of metastases. There may be an association between the vascular density of individual tumors and their prognosis. In the present survey we studied 53 cases of renal cell carcinoma investigating possible relationship between histologic grade and microvessel density (MVD) measured by an image analysis system. According to our results MVD was significantly associated with the histologic grade, higher grades being accompanied with a higher MVD. Further studies are needed to investigate a possible connection of MVD with the prognostic role of grade in RCCs.
C1 [Kavantzas, Nikolaos] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Paraskevakou, Helen] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Tseleni-Balafouta, Sofia] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Aroni, Kyriaki] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Athanassiades, Pauline] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Agrogiannis, George] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, Department of Pathology, 60 Agias Lavras str., GR-157 73 Athens, Greece.
RP Agrogiannis, G (reprint author), University of Athens, Medical School, Department of Pathology, GR-157 73 Athens, Greece.
EM agrogeorge@panafonet.gr
CR Denekamp J, Hobson B: Endothelial-cell proliferation in experimental tumours. Br J Cancer 46: 711-720, 1982
Diaz-Cano SJ, de Miguel M, Blanes A, Galera H, Wolfe HJ: Contribution of the microvessel network to the clonal and kinetic profiles of adrenal cortical proliferative lesions. Hum Pathol 32: 1232-1239, 2001
Gelb A, Sudilovsky D, Daniel Wu C, Weiss L.M, Medeiros JL: Appraisal of intratumoral microvessel density, MIB-1 score, DNA content and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma. Cancer 80: 1768-1775, 1997
Ginnara JR, Ward LM, Porter FD, Wagner JR, Devor DE, Grinberg A, Emmert-Buck MR, Westphal H, Klausner RD, Linehan WM: Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice. Proc Natl Acad Sci USA 94: 9102-9107, 1997
Haigh JJ, Gerber HP, Ferrara N, Wagner EF: Conditional inactivation of VEGF-A in areas of collagen2α1 expression results in embryonic lethality in the heterozygous state. Development 127: 1445-1453, 2000
Heicappell R: Cadherins in renal cell carcinoma. Anticancer Res 19(2C): 1501-1504, 1999
Herbst C, Kosmehl H, Stiller KJ, Berndt A, Eiselt M, Schubert J, Katenkamp B: Evaluation of microvessel density by computerised image analysis in human renal cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity and occurrence of metastasis. J Cancer Res Clin Oncol 124:141- 147, 1998
Imao T, Egawa M, Takashima H, Koshida K, Namiki M: Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma. Int J Urol. 1:948-953, 2004
Joo HJ, Oh DK, Kim YS, Lee KB, Kim SJ: Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int 93:291-296, 2004
McCue PA, Gorstein F: Genetic markers in renal cell carcinomas. Hum Pathol 32: 1027-1028, 2001
MacLennan GT, Bostwick DC: Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology 46:27-30, 1995
Nativ O, Sabo E, Reiss A, Wald M, Madjar S, Moskovitz B: Clinical significance of tumor angiogenesis in patients with localized renal cell carcinoma. Urology 51: 693-696, 1998
Pantuck A, Zeng G, Belldegrun A, Figlin R: Pathobiology, prognosis and targeted therapy for renal cell carcinomas. Clin Cancer Res 9: 4641-4652, 2003
Paraskevakou E, Kavantzas N, Pavlopoulos PM, Delibasis A, Yova D, Davaris P: Computerized nuclear morphometry of renal cell carcinomas. Gen Diagn Pathol 142: 101-104, 1996
Rioux-Leclercq N, Epstein JI, Bansard JY, Turlin B, Botard JJ, Manunta A, Chan T, Ramee MP, Lobel B, Moulinoux JP: Clinical significance of cell proliferation, microvessel density and CD44 adhesion molecule expression in renal cell carcinoma. Hum Pathol 32: 1209-1215, 2001
Tuna B, Yorukoglu K, Unlu M, Mungan MU, Kirkali Z: Association of mast cells with microvessel density in renal cell carcinomas. Eur Urol 50:530-534, 2006
Van Brussel JP, Mickisch GH: Prognostic factors in renal cell and bladder cancer. BJU Int 83: 902-908, 1999
Yagasaki H, Kawata N, Takimoto Y, Nemoto N: Histopathological analysis of angiogenic factors in renal cell carcinoma. Int J Urol 10:220-227, 2003
Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA: A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427-434, 2003
Yoshino S, Kato M, Okada K: Clinical significance of angiogenesis, proliferation and apoptosis in renal cell carcinoma. Anticancer Res 20: 591-594, 2000
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 145
EP 148
PG 4
ER
PT J
AU Bodor, Cs
Schmidt, O
Csernus, B
Rajnai, H
Szende, B
AF Bodor, Csaba
Schmidt, Otto
Csernus, Balazs
Rajnai, Hajnalka
Szende, Bela
TI DNA and RNA Isolated from Tissues Processed by Microwave-Accelerated Apparatus MFX-800-3 are Suitable for Subsequent PCR and Q-RT-PCR Amplification
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE paraffin embedding; MFX-800-3 histoprocessor; real-time PCR; molecular pathology
ID paraffin embedding; MFX-800-3 histoprocessor; real-time PCR; molecular pathology
AB Over the past decade, methods of molecular biology have appeared in diagnostic pathology and are routinely applied on formalin-fixed, paraffin-embedded histological samples, processed via conventional embedding methods. Due to its reagent- and cost-effectiveness, embedding techniques that utilize microwave acceleration in one or more steps of histoprocessing are increasingly used by numerous laboratories. The demand arises that tissues processed this way should also be suitable for the requirements of molecular pathology. In this study, both conventionally embedded and MFX-800-3 machine-processed tissue samples from the same source were used for isolation of DNA and RNA and for performing PCR and real-time PCR. PCR amplification of the beta-globin gene, as well as the real-time PCR amplification of the ABL mRNA was successful in all cases. Our conclusion is that samples processed by the vacuum assisted automatic microwave histoprocessor MFX-800-3 are perfectly applicable for DNA and RNA isolation and provide appropriate templates for further PCR and realtime PCR studies.
C1 [Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Schmidt, Otto] MeditestBudapest, Hungary.
[Csernus, Balazs] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Rajnai, Hajnalka] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM bodor@korb1.sote.hu
CR Beillard E, Pallisgaard N, van der Velden VH, et al: Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction, RQPCR, - a Europe against cancer program. Leukemia 17:2474- 2486, 2003
Benchekroun M, DeGraw J, Gao J, et al: Impact of fixative on recovery of mRNA from paraffin-embedded tissue. Diagn Mol Pathol 13:116-125, 2004
Boon ME, Wals-Paap CH, Visinoni FA, et al: The two-step vacuum- microwave method for histoprocessing. Eur J Morphol 33:349-358, 1995
Coindre JM, Hostein I, Terrier P, et al: Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group. Cancer 107:1055-1064, 2006
Crocker J: Demystified... Molecular pathology in oncology. Mol Pathol 55:337-347, 2002.
Ekuni D, Firth JD, Putnins EE, et al: RNA integrity and in situ RT-PCR in dento-alveolar tissues after microwave accelerated demineralisation. Arch Oral Biol 51:164-169, 2006
Gjerdrum LM, Sorensen BS, Kjeldsen E, et al: Real-time quantitative PCR of microdissected paraffin-embedded breast carcinoma: an alternative method for HER-2/neu analysis. J Mol Diagn 6:42-51, 2004
Hsu HC, Peng SY, Shun CT, et al: High quality of DNA retrieved for Southern blot hybridization from microwavefixed, paraffin-embedded liver tissues. J Virol Methods 31:251-261, 1991
Kok LP, Visser PE, Boon ME, et al: Histoprocessing with the microwave oven: an update. Histochem J 20:323-328, 1988
Kovacs L, Szende B, Elek G, et al: Working experience with a new vacuum-accelerated microwave histoprocessor. J Pathol 180:106-110, 1996
Lou YK, Qin H, Molodysky E, et al: Simple microwave and thermal cycler boiling methods for preparation of cervicovaginal lavage cell samples prior to PCR for human papillomavirus detection. J Virol Methods 44:77-81, 1993
Man YG, Burgar A: An antigen unmasking protocol that satisfies both immunohistochemistry and subsequent PCR amplification. Pathol Res Pract 199:815-825, 2003
Mies C: Molecular biological analysis of paraffin-embedded tissues. Hum Pathol 25:555-560, 1994
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Ryan JL, Fan H, Glaser SL, et al: Epstein-Barr virus quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn 6:378-385, 2004
Vincek V, Nassiri M, Nadji M, et al: A tissue fixative that protects macromolecules, DNA, RNA, and protein, and histomorphology in clinical samples. Lab Invest 83:1427-1435, 2003
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 149
EP 152
PG 4
ER
PT J
AU Sitic, S
Korac, P
Peharec, P
Zovko, G
Perisa, MM
Gasparov, S
AF Sitic, Sanda
Korac, Petra
Peharec, Petra
Zovko, Gojko
Perisa, Milkovic Marija
Gasparov, Slavko
TI Bcl-2 and MALT1 Genes are not Involved in the Oncogenesis of Uterine Tumors Resembling Ovarian Sex Cord Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE uterus; ovarian sex cord tumors; Bcl-2; MALT1; translocation
ID uterus; ovarian sex cord tumors; Bcl-2; MALT1; translocation
AB Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare entities. They were described by Clement and Scully in 1976 who classified them into groups I and II. Group I comprises typical endometrial stromal neoplasms with focal areas resembling ovarian sex cord elements and group II are predominantly or completely composed of ovarian sex cord-like elements. We report a case of UTROSCT type II with cytogenetic analysis. The tumor occurred in a 76-year-old woman who presented with vaginal bleeding. The tumor was lobulated, firm, yellow and histologically composed of sex cord-like elements. Tumor cells expressed vimentin, CD10, CD99 and alpha-actin. Cytogenetic analysis in a previously reported case detected translocation t(4;18)(q21.1;q21.3) in the majority of cells. Bcl-2 and MALT1 genes are located at or near the translocation breakpoints, and the aim of this study was to determine whether these genes were involved in chromosomal translocation or tumorigenesis. We did not find IgH translocation or the most common MALT translocations. Bcl-2 was also not involved in this oncogenesis.
C1 [Sitic, Sanda] “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zajceva 19Zagreb, Croatia.
[Korac, Petra] “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zajceva 19Zagreb, Croatia.
[Peharec, Petra] University Hospital Center Zagreb, Department of PathologyZagreb, Croatia.
[Zovko, Gojko] Clinical Hospital Merkur, University Clinic for Gynecology and Obstetrics, Department of Gynecological OncologyZagreb, Croatia.
[Perisa, Milkovic Marija] “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zajceva 19Zagreb, Croatia.
[Gasparov, Slavko] “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zajceva 19Zagreb, Croatia.
RP Sitic, S (reprint author), “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zagreb, Croatia.
EM sitic.st@inet.hr
CR Baker RJ, Hildebrandt RH, Rouse RV, Hendrickson MR, Longacre TA: Inhibin and CD99, MIC2, expression in uterine stromal neoplasms with sex-cord-like elements. Hum Pathol 30: 671-679, 1999
Busam KJ, Iversen K, Coplan KA, Old LJ, Stockert E, Chen YT, McGregor D, Jungbluth A: Immunoreactivity for A103, an antibody to melanocytic antigen melan-A, Mart-1), in adrenocortical and other steroid tumors. Am J Surg Pathol 22: 57-63, 1998
Clement PB, Scully RE: Uterine tumors resembling ovarian sex-cord tumors. Am J Clin Pathol 66: 512-525, 1976
Fukunaga M, Miayazawa Y, Ushigome S: Endometrial lowgrade stromal sarcoma with ovarian sex cord-like differentiation: report of two cases with an immunohistochemical and flow cytometric study. Pathol Int 47: 412-415, 1977
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J: The World Health Organisation classification of neoplastic diseases of the haematopoetic and lymphoid tissue: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology 36: 69-97, 2000
Hauptmann S, Nadjari B, Kraus J, Turnwald W, Dietel M: Uterine tumor resembling ovarian sex-cord tumor—a case report and review of the literature. Virchows Arch 439: 97-101, 2001
Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA: Method for analysis of cellular DNA content of paraffinembedded pathological material using flow cytometry. J Histochem Cytochem 31: 1333-1335, 1983
Hiddemann W, Schumann J, Andreeff M, Barlogie B, Herman CJ, Leif RC, Mayall BH, Murphy RF, Sandberg AA: Convention on nomenclature for DNA cytometry. Cytometry 5: 445- 446, 1984
Hillard JB, Malpica A, Ramirez PT: Conservative management of a uterine tumor resembling an ovarian sex cord-stromal tumor. Gynecol Oncol 92: 347-352, 2004
Horn LC, Stegner HE: Uteriner Stromatumor mit ovarieller Keimstrangdifferenzierung. Pathologe 16: 421-425,1995
Isaacson PG: Update on MALT lymphomas. Best Pract Res Clin Haematol 18: 57-68, 2005
Kabbani W, Deavers MT, Malpica A, Burke TW, Liu J, Ordonez NG, Jhingran A, Silva EG: Uterine tumor resembling ovarian sex-cord tumor: report of a case mimicking cervical adenocarcinoma. Int J Gynecol Pathol 22: 297-302, 2003
Kantelip B, Cloup N, Dechelotte P: Uterine tumor resembling ovarian sex cord tumors: Report of a case with ultrastructural study. Hum Pathol 17: 91-94, 1986
Krishnamurthy S, Jungbluth AA, Busam KJ, Rosai J: Uterine tumors resembling ovarian sex-cord tumors have an immunophenotype consistent with true sex-cord differentiation. Am J Surg Pathol 22: 1078-1082, 1998
Mazur MT, Kraus FT: Histogenesis of morphologic variations in tumors of the uterine wall. Am J Surg Pathol 4: 59-74, 1980
Suzuki C, Matsumoto T, Fukunaga M, Itoga T, Furugen Y, Kurosaki Y, Suda K, Kinoshita K: Uterine tumors resembling ovarian sex-cord tumors producing parathyroid hormonerelated protein of the uterine cervix. Pathol Int 52: 164-168, 2002
Wang J, Blakey GL, Zhang L, Bane B, Torbenson M, Li S: Uterine tumor resembling ovarian sex cord tumor: report of a case with t(X;6)(p22.3;q23.1, and t(4;18)(q21.1;q21.3). Diagn Mol Pathol 12: 174-180, 2003
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 153
EP 156
PG 4
ER
PT J
AU Csire, M
Mikala, G
Jako, J
Masszi, T
Janosi, J
Dolgos, J
Fule, T
Tordai, A
Berencsi, Gy
Valyi-Nagy, I
AF Csire, Marta
Mikala, Gabor
Jako, Janos
Masszi, Tamas
Janosi, Judit
Dolgos, Janos
Fule, Tibor
Tordai, Attila
Berencsi, Gyorgy
Valyi-Nagy, Istvan
TI Persistent Long-Term Human Herpesvirus 6 (HHV-6) Infection in a Patient with Langerhans Cell Histiocytosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Langerhans cell histiocytosis; eosinophilic granuloma; HHV-6; human herpesviruses; herpesvirus reactivation
ID Langerhans cell histiocytosis; eosinophilic granuloma; HHV-6; human herpesviruses; herpesvirus reactivation
AB Langerhans cell histiocytosis (eosinophilic granuloma) was first diagnosed in the adolescence of a male patient presented. Several years later persisting human herpesvirus 6 (HHV-6) infection was recognized. The HHV-6 infection could be verified retrospectively in his historical histological samples; the continuous presence of HHV-6 could be established through 17 years of disease course. The patient was operated several times during this period for painful relapses, and developed diabetes insipidus. At variable time points during the clinical course, Varicella zoster (VZV), Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) infections were temporarily detected from blood samples and biopsy specimens. HHV-6 was the only virus continuously identified throughout the entire follow-up period. Antiviral therapy effectively cleared EBV and HHV-8, but HHV-6 remained detectable throughout the disease course. Since DNA sequences of HHV-6 could be detected in the pathologic histiocytes of eosinophilic granuloma, and from other samples taken later on, it is suggested that long-term HHV-6 infection may be associated with development or progression of Langerhans cell histiocytosis.
C1 [Csire, Marta] National Center for Epidemiology, Division of Virology, 2-6. Gyali ut, H-1097 Budapest, Hungary.
[Mikala, Gabor] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Jako, Janos] National Medical Center, 1st Department of Internal MedicineBudapest, Hungary.
[Masszi, Tamas] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Janosi, Judit] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Dolgos, Janos] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Fule, Tibor] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular PathologyBudapest, Hungary.
[Tordai, Attila] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Berencsi, Gyorgy] National Center for Epidemiology, Division of Virology, 2-6. Gyali ut, H-1097 Budapest, Hungary.
[Valyi-Nagy, Istvan] National Medical Center, 1st Department of Internal MedicineBudapest, Hungary.
RP Csire, M (reprint author), National Center for Epidemiology, Division of Virology, H-1097 Budapest, Hungary.
EM mcsire@freemail.hu
CR Ahlqvist J, Fotheringham J, Akhyani N, Yao K, Fogdell-Hahn A, Jacobson S: Differential tropism of human herpesvirus 6, HHV-6, variants and induction of latency by HHV-6A in oligodendrocytes. J Neurovirol 11:384-394, 2005.
Aubin JT, Agut H, Collandre A, Yamanishi K, Chandran B, Montagnier L, Huraux J M: Antigenic and genetic differentiation of the two putative types of herpes virus 6. J Virol Methods 41:223-234, 1993.
Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles D M, Moore PS: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865-1869, 1994.
De Bolle L, Naesens L, De Clercq E: Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev 18:217-245, 2005.
Donati D, Martinelli E, Cassiani-Ingoni R, Ahlqvist J, Hou J, Major EO, Jacobson S: Variant-specific tropism of human herpesvirus 6 in human astrocytes. J Virol 79:9439-9448, 2005.
Glotzbecker MP, Carpentieri DF, Dormans JP: Langerhans cell histiocytosis: a primary viral infection of bone? Human herpes virus 6 latent protein detected in lymphocytes from tissue of children. J Pediatr Orthop 24:123-129, 2004.
Glotzbecker MP, Dormans JP, Pawel BR, Wills BP, Josi Y, Elkan M, Hodinka RL: Langerhans cell histiocytosis and human herpesvirus 6, HHV-6), an analysis by real-time polymerase chain reaction. J Ortop Res 24:313-320, 2006.
Ishikawa K, Hasegawa K, Naritomi T, Kanai N, Ogawa M, Kato Y, Kobayashi M, Torii N, Hayashi N: Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan. J Gastroenterol 37:523-530, 2002.
Jenson HB, McClain KL, Leach CT, Deng JH, Gao SJ: Evaluation of human herpesvirus type 8 infection in childhood langerhans cell histiocytosis. Am J Hematol 64:237-241, 2000.
Kakimoto M, Hasegawa A, Fujita S, Yasukawa M: Phenotypic and functional alterations of dendritic cells induced by human herpesvirus 6 infection. J Virol 76:10338-10345, 2002.
Leahy MA, Krejci SM, Frednash M, Stockert SS, Wilson H, Huff JC, Wetson W, Brice SL: Human herpesvirus 6 is present in lesions of Langerhans cell histiocytosis J Invest Dermatol 101:642-645, 1993.
Mitchell SM, Fox JD, Tedder RS, Gazzard BG, Lightman S: Vitreous fluid sampling and viral genome detection for the diagnosis of viral retinitis in patients with AIDS. J Med Virol 43:336-340, 1994.
Pozo F, Tenorio A: Detection and typing of lymphotropic herpesviruses by multiplex polymerase chain reaction. J Virol Methods 79:9-19, 1999.
Renne R, Zhong W, Herndier B, Kedes D, McGrath M, Ganem D: Lytic growth of Kaposi’s sarcoma-associated herpesvirus, human herpesvirus 8, in B cell lymphoma cells in culture. Nat Med 2:342-346, 1996.
Tetsushi Y: Human herpesvirus 6 infection in haematopoetic stem cell transplant patients. Br J Haematol 124:421-432, 2004.
Ward KN: The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the immunocompetent. J Clin Virol 32:183-193, 2005.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 157
EP 160
PG 4
ER
PT J
AU Andreadis, D
Nomikos, A
Barbatis, C
AF Andreadis, Dimitrios
Nomikos, Alexandros
Barbatis, Calypso
TI Metastatic Renal Clear Cell Carcinoma in the Parotid Gland: A Study of Immunohistochemical Profile and Cell Adhesion Molecules (CAMs) Expression in Two Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE metastatic renal cell carcinoma; parotid gland; cell adhesion molecules; immunohistochemistry
ID metastatic renal cell carcinoma; parotid gland; cell adhesion molecules; immunohistochemistry
AB Metastasis of renal cell carcinoma (RCC) may involve any organ, including the parotid salivary gland. While the definition of salivary gland neoplasms with clear cell transformation can be concluded by the synchronous presence of areas showing typical morphology, sometimes the definition of a metastatic RCC in the parotid is difficult and the application of immunohistochemistry may support the clinical and radiographic observations in the final diagnosis. The aim of this paper was to describe the heterogeneous immunohistochemical features and, furthermore, to characterize the pattern of expression of cell adhesion molecules (CAMs) E-cadherin, beta4-integrin, desmoglein-2, ICAM-1 and CD44s (HCAM) in two cases of metastatic parotid RCC.
C1 [Andreadis, Dimitrios] Hellenic Red Cross Hospital of Athens, Department of Histopathology, 4 Sarantaporou St, 155-61 Athens, Greece.
[Nomikos, Alexandros] Hellenic Red Cross Hospital of Athens, Department of Histopathology, 4 Sarantaporou St, 155-61 Athens, Greece.
[Barbatis, Calypso] Hellenic Red Cross Hospital of Athens, Department of Histopathology, 4 Sarantaporou St, 155-61 Athens, Greece.
RP Andreadis, D (reprint author), Hellenic Red Cross Hospital of Athens, Department of Histopathology, 155-61 Athens, Greece.
EM uromorulin@hotmail.com
CR Maiorano E, Altini M, Favia G: Clear cell tumors of the salivary glands, jaws, and oral mucosa. Semin Diagn Pathol 14:203-212, 1997
Hessan H, Strauss M, Sharkey FE: Urogenital tract carcinoma metastatic to the head and neck. Laryngoscope 96:1352-1356, 1986
Adil G, Murat D, Ayhan O, Ozgur TM, Ibrahim Y, Fuat PA, Rifki F: Renal cell carcinoma metastatic to the parotid gland. 83:861-862, 1999
Solitary metastasis of renal cell carcinoma to the parotid gland 10 years after radical nephrectomy. Int J Urol 11:894-896, 2004
Parotid gland metastasis from renal cell carcinoma. Laryngoscope 112:453-456, 2002
Clear cell tumors of salivary glands. Ann Otol Rhinol Laryngol 89:196-197, 1980
Ellis GL, Auclair PL: Tumors of the salivary glands. Washington DC: Armed Forces Institute of Pathology, 1996, pp 281-289
Seijas BP, Franco FL, Sastre RM, Garcia AA, Cempanos JLL: Metastatic renal cell carcinoma presenting as a parotid tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:554-557, 2005
Nappi O, Mills SE, Swanson PE, Wick MR: Clear cell tumors of unknown nature and origin: a systematic approach to diagnosis. Semin Diagn Pathol 14:203-212, 1997
Albelda SM: Biology of disease: Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest 68:4-17, 1993
Pignatelli M, Vessey CJ: Adhesion molecules: Novel molecular tools in tumor pathology. Hum Pathol 25:849-856, 1994
Schafer S, Koch PJ, Franke WW: Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. Exp Cell Res 211:391-399, 1994
Mercurio AM, Rabinovitz I: Towards a mechanistic understanding of tumor invasion—lessons from the alpha6beta4 integrin. Semin Cancer Biol 11:129-141, 2001
Sneath RJS, Mangham DC: The normal structure and function of CD44 and its role in neoplasia. J Clin Pathol: Mol Pathol 51:191- 200, 1998
Thiery JP: The Ig superfamily of adhesion molecules. In Kreis T, Vale R: Guidebook extracellular matrix, anchor and adhesion proteins. 2nd edition, Oxford University Press, 1999, pp 125-128
Ozolek JA, Bastacky SI, Myers EN, Hunt JL: Immunophenotypic comparison of salivary gland oncocytoma and metastatic renal cell carcinoma. Laryngoscope 115:1097-1100, 2005
Rosai J: Rosai and Ackerman’s Surgical Pathology. Ninth Edition. Vol.1. Mosby, London, 2004
Dabbs D: Diagnostic Immunohistochemistry. Churchill Livingstone, New York, 2004
Wang B, Brandwein M, Gordon R, Robinson R, Urken M, Zarbo RJ: Primary salivary clear cell tumors—a diagnostic approach: a clinicopathologic and immunohistochemical study of 20 patients with clear cell carcinoma, clear cell myoepithelial carcinoma, and epithelial-myoepithelial carcinoma. Arch Pathol Lab Med 126:676- 685, 2002
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 161
EP 165
PG 5
ER
PT J
AU Perez, EdCD
Magrin, J
de Almeida, PO
Kowalski, PL
AF Perez, Elias da Cruz Danyel
Magrin, Jose
de Almeida, Paes Oslei
Kowalski, Paulo Luiz
TI Multiple Cutaneous Metastases from a Parotid Adenoid Cystic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adenoid cystic carcinoma; cutaneous metastasis; cancer; cytokeratin; histopathology; immunohistochemistry
ID adenoid cystic carcinoma; cutaneous metastasis; cancer; cytokeratin; histopathology; immunohistochemistry
AB Cutaneous metastasis from salivary gland adenoid cystic carcinoma is extremely rare. We report a case of a 39-year-old man that presented multiple cutaneous metastases from a parotid salivary gland adenoid cystic carcinoma. The clinical, histopathological and immunohistochemical features are described and discussed. This case shows the importance of a detailed and periodical skin examination in patients treated for salivary gland adenoid cystic carcinoma.
C1 [Perez, Elias da Cruz Danyel] A. C. Camargo Cancer Hospital, Department of Stomatology, Rua Professor Antonio Prudente, 211. Liberdade, 01509-900 Sao Paulo, Brazil.
[Magrin, Jose] A. C. Camargo Cancer Hospital, Department of Head and Neck Surgery and OtorhinolaryngologySao Paulo, Brazil.
[de Almeida, Paes Oslei] University of Campinas, School of Dentistry of Piracicaba, Department of Oral PathologySao Paulo, Brazil.
[Kowalski, Paulo Luiz] A. C. Camargo Cancer Hospital, Department of Head and Neck Surgery and OtorhinolaryngologySao Paulo, Brazil.
RP Perez, EdCD (reprint author), A. C. Camargo Cancer Hospital, Department of Stomatology, 01509-900 Sao Paulo, Brazil.
EM perezdec2003@yahoo.com.br
CR Alcedo JC, Fabrega JM, Arosemena JR, Urrutia A: Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases. Head Neck 26:829-831, 2004
Araujo VC, Sousa SOM, Carvalho, Araujo NS: Application of immunohistochemistry to the diagnosis of salivary gland tumors. Appl Immunohistochem Mol Morphol 8:195-202, 2000
Chang CH, Liao YL, Hong HS: Cutaneous metastasis from adenoid cystic carcinoma of the parotid gland. Dermatol Surg 29:775-779, 2003
Doganay L, Bilgi S, Aygit C, Altaner S: Primary cutaneous adenoid cystic carcinoma with lung and lymph node metastases. J Eur Acad Dermatol Venereol 18:369-371, 2004
Ellis GL, Auclair P: Tumors of the salivary glands: Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology, 3rd Series, Fascicle 17, 1996
Holst VA, Marshall CE, Moskaluk CA and Frierson HF Jr: KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod Pathol 12:956-960, 1999
Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL: Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: A Princess Margaret Hospital phase II consortium study. J Clin Oncol 23:585-90, 2005
Khan AJ, DiGiovanna MP, Ross DA, Sasaki CT, Carter D, Son YH, Haffty BG: Adenoid cystic carcinoma: a retrospective clinical review. Int J Cancer 96:149-158, 2001
Kokemueller H, Eckardt A, Brachvogel P, Hausamen JE: Adenoid cystic carcinoma of the head and neck – a 20 years experience. Int J Oral Maxillofac Surg 33:25-31, 2004
Lin CH, Yen RF, Jeng YM, Tzen CY, Hsu C, Hong RL: Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate. Head Neck 27:1022-1027, 2005
Nakamura M, Miyachi Y: Cutaneous metastasis from an adenoid cystic carcinoma of the lacrimal gland. Br J Dermatol 141:350-351, 1999
Nascimento AG, Amaral ALP, Prado LAF, Kligerman J, Silveira TR: Adenoid cystic carcinoma of the salivary glands. A study of 61 cases with clinicopathologic correlation. Cancer 57:312-319, 1986
Schwartz RA: Cutaneous metastatic disease. J Am Acad Dermatol 33:161-182, 1995
Spiers AS, Esseltine DL, Ruckdeschel JC, Davies JN, Horton J: Metastatic adenoid cystic carcinoma of salivary glands. Case reports and review of the literature. Cancer Control 3:336-342, 1996
Spiro RH: Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 174:495-498, 1997
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 167
EP 169
PG 3
ER
PT J
AU Sari, A
Uyaroglu, AM
Ermete, M
Oder, M
Girgin, C
Dincer, C
AF Sari, Aysegul
Uyaroglu, Ali Mehmet
Ermete, Murat
Oder, Mehmet
Girgin, Cengiz
Dincer, Cetin
TI Microcystic Urothelial Carcinoma of the Urinary Bladder Metastatic to the Penis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Urothelial carcinoma; microcystic variant; primary bladder cancer; penile metastasis
ID Urothelial carcinoma; microcystic variant; primary bladder cancer; penile metastasis
AB Metastatic spread of primary bladder cancer to the penis is an extremely rare event. Microcystic urothelial carcinoma is a very rare variant of urothelial carcinoma. Due to its rareness and insufficient clinical follow-up data, the prognosis of microcystic urothelial carcinoma is still not clear. Here in we report a case of a penile metastasis from microcystic urothelial carcinoma of urinary bladder, in a 56-year-old man who died 6 months after radical cystoprostatectomy and total penectomy. To the best of our knowledge this is the first case report of microcystic variant of urothelial carcinoma which has metastasized to the penis.
C1 [Sari, Aysegul] Izmir Ataturk Training and Research Hospital, Department of Pathology, Ataturk caddesi, Firat apt. No: 184, Kat: 3, Daire: 6, 35220 Izmir, Alsancak, Turkey.
[Uyaroglu, Ali Mehmet] Izmir Ataturk Training and Research Hospital, Department of Pathology, Ataturk caddesi, Firat apt. No: 184, Kat: 3, Daire: 6, 35220 Izmir, Alsancak, Turkey.
[Ermete, Murat] Izmir Ataturk Training and Research Hospital, Department of Pathology, Ataturk caddesi, Firat apt. No: 184, Kat: 3, Daire: 6, 35220 Izmir, Alsancak, Turkey.
[Oder, Mehmet] Izmir Ataturk Training and Research Hospital, Department of 1st UrologyIzmir, Turkey.
[Girgin, Cengiz] Izmir Ataturk Training and Research Hospital, Department of 1st UrologyIzmir, Turkey.
[Dincer, Cetin] Izmir Ataturk Training and Research Hospital, Department of 1st UrologyIzmir, Turkey.
RP Sari, A (reprint author), Izmir Ataturk Training and Research Hospital, Department of Pathology, 35220 Izmir, Turkey.
EM aysegulakder@gmail.com
CR Khan MA, Tao W, Mathews P, Potluri BS: Penile metastasis arising from transitional cell carcinoma of the urinary bladder. Urol Int 66:162-163, 2001
Haddad FS: Tumors of the bladder. Annu Rep Orient Hosp 12:8-19, 1959
Young RH, Eble JN: Unusual forms of carcinoma of the urinary bladder. Hum Pathol 22:948-965, 1991
Young RH, Zukerberg LR: Microcystic transitional cell carcinomas of the urinary bladder. A report of four cases. Am J Clin Pathol 96:635-639, 1991
Paz A, Rath-Wolfson L, Lask D, Koren R, Manes A, Mukamel E, Gal R: The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases. Br J Urol 79:722-725, 1997
Leroy X, Leteurtre E, De La Taille A, Augusto D, Biserte J, Gosselin B: Microcystic transitional cell carcinoma: a report of 2 cases arising in the renal pelvis. Arch Pathol Lab Med 126:859-861, 2002
Radopoulos D, Kalyvas K, Kotakidou R, Panagiotopoulou K, Katsikas V, Papathanasiou M: Case report: microcystic transitional cell carcinoma of the urinary bladder. Int Urol Nephrol 37:291-293, 2005
Pomara G, Pastina I, Simone M, Casale P, Marchetti G, Francesca F: Penile metastasis from primary transitional cell carcinoma of the renal pelvis: first manifestation of systemic spread. BMC Cancer 4:90, 2004
Demuren OA, Koriech O: Isolated penile metastasis from bladder carcinoma. Eur Radiol 9:1596-1598, 1999
Osther PJ, Lontoft E: Metastasis to the penis. Case reports and review of the literature. Int Urol Nephrol 23:161-167, 1991
Haddad FS: Penile metastases secondary to bladder cancer. Review of the literature. Urol Int 39:125-142, 1984
Berger AP, Rogatsch H, Hoeltl L, Steiner H, Bartsch G, Hobisch A: Late penile metastasis from primary bladder carcinoma. Urology 62:145, 2003
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2007
VL 13
IS 2
BP 170
EP 173
PG 4
ER
PT J
AU Beser, RA
Tuzlali, S
Guzey, D
Dolek Guler, S
Hacihanefioglu, S
Dalay, N
AF Beser, Rehber Asli
Tuzlali, Sitki
Guzey, Deniz
Dolek Guler, Semra
Hacihanefioglu, Seniha
Dalay, Nejat
TI HER-2, TOP2A and Chromosome 17 Alterations in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TOP2A; HER-2; breast cancer
ID TOP2A; HER-2; breast cancer
AB HER-2 amplification is a biomarker for identifying patients who respond to trastuzumab and has been evaluated as a factor predicting the response to anthracyclines. The relationship between HER-2 and response to anthracycline therapy may also be the result of the close localization of TOP2A on 17q. It has been a matter of debate whether these two genes, HER-2 and TOP2A, behave separately on different amplicons or act together thus making it possible to predict the TOP2A status from the HER-2 status. In this study TOP2A, HER-2 and chromosome 17 aneusomy were investigated by fluorescent in situ hybridization (FISH) in 50 consecutive breast cancer patients. HER-2 amplification was detected in 11 patients (22%) and TOP2A changes were seen in 6 patients (12%); two amplifications and two deletions were observed in HER-2-amplified cases and two deletions in HER-2-nonamplified cases. Three of the TOP2A-deleted cases had polysomy 17. HER-2 copy number was higher than the TOP2A copy number in one patient with co-amplification. Polysomy was observed in 9 cases (18%) and monosomy in 6 cases (12%). Aneusomy was the sole anomaly in 11 patients (22%). We conclude that the TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy. Other factors modulating topo II activity may also affect the response to therapy. Studies evaluating different parameters that can modulate topo II activity and the response to the drugs targeting the enzyme are necessary.
C1 [Beser, Rehber Asli] Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34093 Istanbul, Capa, Turkey.
[Tuzlali, Sitki] Istanbul Medical Faculty, Department of PathologyIstanbul, Turkey.
[Guzey, Deniz] Vakif Gureba Hospital, Department of SurgeryIstanbul, Turkey.
[Dolek Guler, Semra] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Hacihanefioglu, Seniha] Istanbul Medical Faculty, Istanbul University, Department of Medical BiologyIstanbul, Turkey.
[Dalay, Nejat] Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34093 Istanbul, Capa, Turkey.
RP Dalay, N (reprint author), Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34093 Istanbul, Turkey.
EM ndalay@yahoo.com
CR Bhargava R, Lal P, Chen B: HER-2/neu and topoisomerase IIα gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol 123:889-895, 2005
Biersack H, Jensen S, Gromova I, Nielsen IS, Westergaard O: Active heterodimers are formed from human topoisomerase II alpha and II beta isoforms. Proc Natl Acad Sci USA 93: 8288- 8293, 1996
Bose S, Mohammed M, Shintaku P, Rao PN: Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy. Breast J 7:337-344, 2001
Burden DA, Osheroff N: Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochim Biophys Acta 1400:139-154, 1999
Cardoso F, Durbecq V, Larsimont D, Paesmans M, Leroy JY, Rouas G, Sotiriou C, Renard N, Richard V, Picaart MJ, Di Leo A: Correlation between complete response to anthracyclinebased chemotherapy and topoisomerase II alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int J Oncol 24: 201-209, 2004
Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD: Amplification and overexpression of topoisomerase II predict response to anthracyclinebased therapy in locally advanced breast cancer. Clin Cancer Res 8: 1061-1067, 2002
Di Leo A, Gancberg D, Larsimont D, Tanner M, Jarvinen T, Rouas G, Dolci S, Leroy JY, Paesmans M, Isola J, Piccart MJ: HER-2 amplification and topoisomerase II? gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 8: 1107-1116, 2002
Downs-Kelly E, Yoder BJ, Stoler M, Tubbs RR, Skacel M, Grogan T, Roche P, Hicks DG: The influence of polysomy 17 on HER2 gene and protein expression in adenocarcinoma of the breast: A fluorescent in situ hybridization, immunohistochemical, and isotopic mRNA in situ hybridization study. Am J Surg Pathol 29:1221-1227, 2005
Durbecq V, Desmed C, Paesmans M, Cardoso F, Di Leo A, Mano M, Rouas G, Leroy JY, Sotiriou C, Piccart M, Larsimont D: Correlation between topoisomerase-IIalpha gene amplification and protein expression in HER-2 amplified breast cancer. Int J Oncol 25:1473-1479, 2004
Faneyte IF, Chrama JO, Peterse JL, Remijse JL, Rodenhuis S, Van der Vijver MJ: Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 88: 406-412, 2003
Fehm T, Morrison L, Saboorian H, Hynan L, Tucker T, Uhr J: Patterns of aneusomy for three chromosomes in individual cells from breast cancer tumors. Breast Cancer Res Treat 75: 227- 239, 2002
Greenlee RT, Hill-Harmon MB, Murray T, Thun M: Cancer Statistics 2001. CA Cancer J Clin 51:15-36, 2001
Harris LN, Yang L, Liotcheva V, Pauli S, Iglehart JD, Colvin OM, Hsieh TS: Induction of topoisomerase II activity after ERbB2 activation is associated with a differential response to breast cancer chemotherapy. Clin Cancer Res 7: 1497-1504, 2001
Hicks DG, Yoder BJ, Pettay J, Swain E, Tarr S, Hartke M, Skacel M, Crowe JP, Budd GT, Tubbs RR: The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of the breast and their relationship to human epidermal growth factor receptor-2 gene amplification: a fluorescence in situ hybridization study. Hum Pathol 36:348-356, 2005
Hoffken K: The European Experience. J Clin Oncol 19: 112- 117, 2001
Jacobson KK, Morrison LE, Henderson BT, Blondin BA, Wilber KA, Legator MS, O’Hare A, Van Stedum SC, Proffitt JH, Seelig SA, Coon JS Gene copy mapping of the ERBB2/TOP2A region in breast cancer. Genes Chromosomes Cancer 40:19-31, 2004
Jarvinen TA, Holli K, Kuukasjarvi T, Isola JJ: Predictive value of topoisomerase II alpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer. Br J Cancer 77: 2267-2273, 1998
Jarvinen TAH, Liu ET: HER-2/neu and Topoisomerase IIa – simultaneous drug targets in cancer. Comb Chem High Throughput Screen 6: 79-99, 2003
Jarvinen TAH, Liu ET: Topoisomerase IIα gene, TOP2A, amplification and deletion in cancer – more common than anticipated. Cytopathology 4:309-313, 2003
Jarvinen TAH, Tanner M, Barlund M, Borg A, Isola J: Characterization of topoisomerase IIα gene amplification and deletion in breast cancer: Genes Chromosomes Cancer 26:142-150, 1999
Jarvinen TAH, Tanner M, Rantanen V, Barlund M, Borg A, Grenman S, Isola J: Amplification and deletion of topoisomerase IIα associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol 156: 839-847, 2000
Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P: Culprit and victim – DNA topoisomerase II. Lancet Oncol 3:235-243, 2002
Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdottir K, Olsen KE, Mouridsen H, Ejlertsen B; Danish Breast Cancer Cooperative Group: Retrospective analysis of topoisomerase IIα amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol 23:7483-7490, 2005
MacGrogan G, Rudolph P, de Mascarel I, Maurica L, Durand M, Avril A, Dilhudy JM, Robert J, Mathoulin-Pelissier S, Picot V, Floquet A, Serankowski G, Coindre JM: DNA topoisomerase II alpha expression and the response to primary chemotherapy in breast cancer. Br J Cancer 89: 666-667, 2003
Martin-Richard M, Munoz M, Albanell J, Colomo L, Bellet M, Rey MJ, Tabernero J, Alonso C, Cardesa A, Gascon P, Fernandez PL: Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy. Oncology 66: 388-394, 2004
Mueller RE, Parkes RK, Andrulis I, O’Malley FP: Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples. Genes Chromosomes Cancer 39:288-297, 2004
Nakopoulou L, Giannopoulou I, Trafalis D, Gakiopoulou H, Keramopoulos A, Davaris P: Evaluation of numeric alterations of chromosomes 1 and 17 by in situ hybridisation in invasive breast carcinoma with clinicopathologic parameters. Appl Immunohistochem Mol Morphol 10:20-28, 2002
Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, Fisher ER, Lippman ME, Wickerham DL, Wolmark N: erbB2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst 90: 1320-1327,1998
Petit T, Wilt M, Velten M, Millon R, Rodier JF, Borel C, Mors R, Haegele P, Eber M, Ghnassia JP: Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer 40: 205-211, 2004
Ross JS, Fletcher JA: HER-2/neu, c-erb-B2, gene and protein in breast cancer. Am J Clin Pathol 112(Suppl 1):53-67, 1999
Ross JS, Fletcher JA, Bloom KJ, Linette GP, Stec J, Symmans WS, Pusztai L, Hortobagyi GN. Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics 3: 379-398, 2004
Salido M, Tusquets I, Corominas JM, Suarez M, Espinet B, Corzo C, Bellet M, Fabregat X, Serrano S, Sole F: Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry. Breast Cancer Res 7:267-273, 2005
Tanner M, Jarvinen P, Isola J: Amplification of HER-2/neu and topoisomerase IIα in primary and metastatic breast cancer. Cancer Res 61: 5345-5348, 2001
Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, Barcos M, Cirrincione C, Edgerton S, Allred C, Norton L, Liu ET: ERbB-2, p53, and efficacy of adjuvant therapy in lymph nodepositive breast cancer. J Natl Cancer Inst 90: 1346-1360, 1998
Varshney D, Zhou YY, Geller SA, Alsabeh R: Determination of HER-2 status and chromosome 17 polysomy in breast carcinomas comparing HercepTest and PathVysion FISH assay. Am J Clin Pathol 121:70-77, 2004
Wang S, Hossein Saboorian M, Frenkel EP, Haley BB, Siddiqui MT, Gokaslan S, Hynan L, Ashfaq R: Aneusomy 17 in breast cancer: its role in HER-2/neu protein expression and implication for clinical assessment of HER-2/neu status. Mod Pathol 15:137-45, 2002
Watters AD, Going JJ, Cooke TG, Bartlett JMS: Chromosome 17 aneusomy is associated with poor prognostic factors in invasive breast carcinoma. Breast Cancer Res Treat 77: 109-114, 2003
Zhang F, Yang Y, Smith T, Kau SW, McConathy JM, Esteva FJ, Kuerer HM, Symmans WF, Buzdar AU, Hortobagyi GN, Pusztai L: Correlation between HER-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide in patients with breast carcinoma. Cancer 97:1758-1765, 2003
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 180
EP 185
PG 6
ER
PT J
AU Riesz, P
Lotz, G
Paska, Cs
Szendroi, A
Majoros, A
Nemeth, Zs
Torzsok, P
Szarvas, T
Kovalszky, I
Schaff, Zs
Romics, I
Kiss, A
AF Riesz, Peter
Lotz, Gabor
Paska, Csilla
Szendroi, Attila
Majoros, Attila
Nemeth, Zsuzsanna
Torzsok, Peter
Szarvas, Tibor
Kovalszky, Ilona
Schaff, Zsuzsa
Romics, Imre
Kiss, Andras
TI Detection of Bladder Cancer from the Urine using Fluorescence in situ Hybridization Technique
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bladder cancer; cystoscopy; fluorescence in situ hybridization; molecular pathology
ID bladder cancer; cystoscopy; fluorescence in situ hybridization; molecular pathology
AB The authors report on their first experiences with the UroVysion fluorescence in situ hybridization (FISH) kit developed for the detection of bladder cancer. This new non-invasive diagnostic application of the FISH technique in the field of urology was elaborated to replace cystoscopy. The special urine examination method detects genetic alterations of the urothelial cells found in the urine, using fluorescent directlabeled DNA probes binding to the peri-centromeric regions of chromosomes 3, 7 and 17 as well as on the 9p21 locus. We aimed to evaluate the utility of UroVysion test in the light of the histological diagnosis. Urine samples from 43 bladder cancer patients and 12 patients with no or benign alterations were studied using a new application of FISH technique: the UroVysion reagent kit. The obtained FISH results were compared with the histological findings of the transurethral surgical resection specimens. The study rated the specificity and sensitivity of the technique 100% and 87%, respectively. Therefore, the technique could well fit into the diagnostic process of bladder carcinomas. Statistical analyses showed significant correlation between tumor progression and the severity of the genetic alterations detected by this FISH technique. Furthermore, positive correlation was found between tumor grade and the proportion of tumor cells showing genetic abnormality. The noninvasiveness, the robustness of evaluation and the high specificity/sensitivity are all in favor of this technique. The disadvantages are the higher costs of the technical background and the required future clinical studies to determine whether this technique can replace cystoscopy.
C1 [Riesz, Peter] Semmelweis University, Department of UrologyBudapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Paska, Csilla] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Szendroi, Attila] Semmelweis University, Department of UrologyBudapest, Hungary.
[Majoros, Attila] Semmelweis University, Department of UrologyBudapest, Hungary.
[Nemeth, Zsuzsanna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Torzsok, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Szarvas, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
[Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., H-1091 Budapest, Hungary.
RP Lotz, G (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM beka@korb2.sote.hu
CR Droller M.J: Bladder cancer: state-of-the-art care. Ca: Cancer J Clin 48: 269-284, 1998
Oosterlinck W, Lobel B, Jakse G, Malmstrom PU, Stockle M, Sternberg C: Guidelines on bladder cancer. Eur Urol 41: 105- 112, 2002
Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD, Hawkins IR: Superficial bladder cancer progression et recurrence. J Urol 130: 1083-1086, 1983
Halling KC, King W, Sokolova IA, Meyer RG, Burkhardt HM, Halling AC, Cheville JC, Sebo TJ, Ramakumar S, Stewart CS, Pankratz S, O’Kane DJ, Seelig SA, Lieber MM, Jenkins RB: A comparison of cytology and fluorescence in situ hybridization for the detection of bladder cancer. J Urol 164: 1768-1775, 2000
Halling KC, King W, Sokolova IA, Karnes RJ, Meyer RG, Powell EL, Sebo TJ, Cheville JC, Clayton AC, Krajnik KL, Ebert TA, Nelson RE, Burkhardt HM, Ramakumar S, Stewart CS, Pankratz VS, Lieber MM, Blute ML, Zincke H, Seelig SA, Jenkins RB, O'Kane DJ: A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine. J Urol 167: 2001-2006, 2002
Bollmann M, Heller H, Bankfalvi A, Griefingholt H, Bollmann R: Quantitative molecular urinary cytology by fluorescence in situ hybridization: a tool for tailoring surveillance of patients with superficial bladder cancer? BJU Int 95: 1219-1225, 2005
Parkin DM, Pisani P, Ferlay J: Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 80: 827- 841, 1999
Glas AS, Roos D, Deutekom M, Zwinderman AH, Bossuyt PM, Kurth KH: Tumor markers in the diagnosis of primary bladder cancer. A systematic review. J Urol 169: 1975-1982, 2003
Grossman HB: New methods for detection of bladder cancer. Semin Urol Oncol 16: 17-22, 1998
Slaton JW, Dinney CP, Veltri RW, Miller CM, Liebert M, O’Dowd GJ, Grossman HB: Deoxyribonucleic acid ploidy enhances the cytological prediction of recurrent transitional cell carcinoma of the bladder. J Urol 158: 806-811, 1997
van Poppel H, Billen J, Goethuys H, Elgamal AA, Gerits M, Mortelmans L, Blanckaert N, Baert L: Serum tissue polypeptide antigen, TPA, as a tumor marker for bladder cancer. Anticancer Res 16: 2205-2208, 1996
Zhang FF, Arber DA, Wilson TG, Kawachi MH, Slovak ML: Toward the validation of aneusomy detection by fluorescence in situ hybridization in bladder cancer: comparative analysis with cytology, cytogenetics, and clinical features predicts recurrence and defines clinical testing limitations. Clin Cancer Res 3: 2317-2328, 1997
Mao L, Schoenberg MP, Scicchitano M, Erozan YS, Merlo A, Schwab D, Sidransky D: Molecular detection of primary bladder cancer by microsatellite analysis. Science 271: 659-662, 1996
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Skacel M, Fahmy M, Brainard JA, Pettay JD, Biscotti CV, Liou LS, Procop GW, Jones JS, Ulchaker J, Zippe CD, Tubbs RR: Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. J Urol 169: 2101-2105, 2003
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 187
EP 194
PG 8
ER
PT J
AU Suba, Zs
AF Suba, Zsuzsanna
TI Gender-Related Hormonal Risk Factors for Oral Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE oral cancer; fasting glucose; insulin resistance; estrogen deficiency; gender difference
ID oral cancer; fasting glucose; insulin resistance; estrogen deficiency; gender difference
AB Oral cancer (OC) is a neoplasm with fairly high male to female ratio in most populations. The conspicuously lower incidence of this tumor among women than man is suggestive of certain endocrine involvement in its development. The aim of the present case-control study was to clarify the origin of this gender-specific risk of OC incidence. 2660 inpatients (530 females and 2130 males) with squamous cell OC at the Department of Oral and Maxillofacial Surgery were included in a case-control study. Smoking, alcohol consumption, elevated fasting serum glucose level and menopausal histories of female cases were registered. Smoking and excessive alcohol intake proved to be strong risk factors for OC both in the male and female group. However, moderate alcohol consumption was a weaker risk factor for male patients, and it presented no risk for female cases. Elevated fasting glucose level was not a demonstrable OC risk factor among males, however, it proved to be strong risk factor for OC among female patients, especially in gingival cancer cases. The almost exclusively postmenopausal state of female OC patients and the long mean interval (17 years) between their menopause and OC diagnosis suggested an important role of estrogen deficiency in OC epidemiology. The significantly younger mean age at menopause and the significantly higher rate of hysterectomy among female OC cases in comparison with their controls also support the estrogen deficiency hypothesis. This novel hypothesis of estrogen deficiency and elevated fasting glucose as risk factors for OC in postmenopausal women may provide new insights into the etiology of oral malignancies.
C1 [Suba, Zsuzsanna] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria u. 52., H-1085 Budapest, Hungary.
RP Suba, Zs (reprint author), Semmelweis University, Department of Oral and Maxillofacial Surgery, H-1085 Budapest, Hungary.
EM suba@szajseb.sote.hu
CR Neville BW, Day TA: Tumors and precancerous lesions of the oral cavity. CA Cancer J Clin 52: 195-215, 2002
La Vecchia C, Lucchini F, Negri E et al: Trends in oral cancer mortality in Europe. Oral Oncol 40: 433-439, 2004
Krolls SO, Hoffman S: Squamous cell carcinoma of the oral soft tissues: a statistical analysis of 14,253 cases by age, sex and race of patients. JADA 92: 571-574, 1976
Rich AM, Radden BG: Squamous cell carcinoma of the oral mucosa: a review of 244 cases in Australia. J Oral Pathol 13: 459-471, 1984
Levi F, Lucchini F, Negri E et al: Trends in cancer mortality in the European Union and accession countries, 1980-2000. Ann Oncol 15: 1425-1431, 2004
Johnson NW: Etiology and risk factors for oral cancers and their correlations with smoking and alcohol consumption. Hung Oncol, in Hungarian, 45: 115-122, 2001
Suba Z, Barabas J: Prevention of oral cancer, in Hungarian). Medicina ZRT, Budapest, 2007, pp. 15-20
Ujpal M, Matos O, Bibok G, et al: Diabetes and oral tumors in Hungary: Epidemiological correlations. Diabetes Care 27: 770- 774, 2004.
Suba Z, Barabas J, Szabo G, et al: Increased prevalence of diabetes and obesity in patients with salivary gland tumors. Diabetes Care 28: 228, 2005
Mealey BL, Moritz AJ: Hormonal influences: effects of diabetes mellitus and endogenous female sex steroid hormones on the periodontium. Periodontol 2000 32: 59-81, 200311. Eliasson B, Attval S, Taskinen MR, et al: The insulin resistance syndrome in smokers is related to smoking habits. Arterioscler Thromb 14: 1946-1950, 1994 12. Sierksma A, Patel H, Ouchi N, et al: Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor alpha and insulin sensitivity. Diabetes Care 24: 184-189, 2004 13. Beulens JW, Stolk RP, van der Schouw YT et al: Alcohol consumption and risk of type-2 diabetes among older women. Diabetes Care 28: 2933-2938, 2005 14. Nestler JE: Obesity, insulin, sex steroids and ovulation. Int J Obes Relat Metab Disord 24, Suppl 2): S71-S73, 2000 15. Huber JC, Schneeberger C, Tempfer CB: Genetic modelling of the estrogen metabolism as risk factor of hormone-dependent disorders. Maturitas 42: 1-12, 2002 16. Liehr JG: Is estradiol a genotoxic mutagenic carcinogen? Endocrine Rev 21: 40-54, 2000 17. Fernandez E, Gallus S, Bosetti C et al: Hormone replacement therapy and cancer risk: a systematic analysis from a network of case-control studies. Int J Cancer 105: 408-412, 2003 18. Diamanti-Kandarakis E: Hormone replacement therapy and risk of malignancy. Curr Opin Obstet Gynecol 16: 73-78, 2004 19. Ettinger B, Friedman GD, Bush T, Qusenberry CP, Jr: Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol 87: 6-12, 1996 20. Gallus S, Bosetti C, Franceschi S et al: Oesophageal cancer in women: tobacco, alcohol, nutritional and hormonal factors. Br J Cancer 85: 341-345, 2001 21. La Vecchia C, D’Avanzo B, Franceschi S et al: Menstrual and reproductive factors and gastric-cancer risk in women. Int J Cancer 59: 761-764, 1994 22. Parazzini F, La Vecchia C, Negri E et al: Case-control study of estrogen replacement therapy and risk of cervical cancer. Br Med J 315: 85-88, 1997 23. Grodstein F, Clarkson T, Manson J: Understanding the divergent data on postmenopausal hormone therapy. N Eng J Med 348: 645-650, 2003 24. Olsson H, Bladstrom AM, Ingvar C: Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Obstet Gynecol 102: 565-570, 2003 25. Reckelhoff JF: Sex steroids, cardiovascular disease, and hypertension. Hypertension 45: 170-180, 2005 26. Austad SN: Why women live longer than men: Sex differences in longevity. Gender Med 3: 79-92, 2006 27. Ebbert JO, Janney CA, Sellers TA et al: The association of alcohol consumption with coronary heart disease mortality and cancer incidence varies by smoking history. J Gener Intern Med 20: 14-20, 2005 28. McGrath M, Michaud DS, De Vivo I: Hormonal and reproductive factors and the risk of bladder cancer in women. Am J Epidemiol 163: 236-244, 2006 29. Gago-Domingez M, Castelao JE, Yuan JM et al: Increased risk of renal cell carcinoma subsequent to hysterectomy. Cancer Epidemiol Biomarkers Prev 8: 999-1003, 1999 30. Faustini-Fustini M, Rochira V, Carani C: Oestrogen deficiency in men: where are we today? Eur J Endocrinol 140: 111-129, 1999 31. McKeown-Eyssen G: Epidemiology of colorectal cancer revisited: are serum triglycerides and plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 3: 687-695, 1994 32. Everhart J, Wright D: Diabetes mellitus as a risk factor for pancreatic cancer: a meta-analysis. JAMA 273: 1605-1609, 1995 33. Balkau B, Kahn H, Courbon D et al: Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: The Paris Prospective Study. Diabetes Care 24: 843-849, 2001 34. Yeung NG, Husain I, Waterfall N: Diabetes mellitus and bladder cancer – An epidemiological relationship? Pathol Oncol Res 9: 30-31, 2003 35. Barnard RJ, Aronson WJ, Tymchuk CN et al: Prostate cancer: another aspect of the insulin-resistance syndrome. Obes Rev 3: 303-308, 2002 36. Muti P, Quattrin T, Grant BJB et al: Fasting glucose is a risk factor for breast cancer. Cancer Epidemiol Biomarkers Prev 11: 1361-1368, 2002 37. Key TJ, Applyby PN, Reeves GK: Body mass index, serum sex hormones and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95: 1218-1226, 2003 38. Soliman PT, Oh JC, Schmeler KM et al: Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 105: 575-580, 2005 39. Solomon CG, Hu FB, Dunaif A et al: Long or highly irregular menstrual cycles as a marker for risk of type-2 diabetes mellitus. JAMA 286: 2421-2426, 2001 40. Bloomgarden ZT: Second World Congress on the Insulin Resistance Syndrome: Mediators, pediatric insulin resistance, the polycystic ovary syndrome, and malignancy. Diabetes Care 28: 1821-1830, 2005 41. Godsland IF: Oestrogens and insulin secretion. Diabetologia 48: 2213-2220, 2005 42. Jones ME, Thorburn AW, Britt KL et al: Aromatase-deficient, ArKO, mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA 97: 12735-12740, 2000 43. Gadducci A, Gargini A, Palla E et al: Polycystic ovary syndrome and gynecological cancers: is there a link? Gynecol Endocrinol 20: 200-208, 2005 44. Freiberg MS, Cabral HJ, Heeren TC: Alcohol consumption and the prevalence of the metabolic syndrome in the US.: A cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey. Diabetes Care 27: 2954- 2959, 2004 45. Onland-Moret NC, Peeters PHM, van der Schouw YT et al: Alcohol and endogenous sex steroid levels in postmenopausal women: A Cross-Sectional Study. J Clin Endocrinol Metab 90: 1414-1419, 2005 46. Tavani A, Gallus S, La Vecchia C et al: Diet and risk of oral and pharyngeal cancer. An Italian case-control study. Eur J Cancer Prev 10: 191-195, 2001
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 195
EP 202
PG 8
ER
PT J
AU Perez-Gutierrez, S
Gonzalez-Campora, R
Amerigo-Navarro, J
Beato-Moreno, A
Sanchez-Leon, M
Pareja Megia, MJ
Virizuela-Echaburu, AJ
Lopez-Beltran, A
AF Perez-Gutierrez, Sofia
Gonzalez-Campora, Ricardo
Amerigo-Navarro, Joaquin
Beato-Moreno, Antonio
Sanchez-Leon, Maria
Pareja Megia, Maria Jesus
Virizuela-Echaburu, Antonio Juan
Lopez-Beltran, Antonio
TI Expression of P-glycoprotein and Metallothionein in Gastrointestinal Stromal Tumor and Leiomyosarcomas. Clinical Implications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastrointestinal stromal tumors; GIST; leiomyosarcomas; P-glycoprotein; metallothionein
ID gastrointestinal stromal tumors; GIST; leiomyosarcomas; P-glycoprotein; metallothionein
AB We investigated the expression of P-glycoprotein (P-GP) and metallothionein (MT) in a series of 92 GIST and 14 gastrointestinal leiomyosarcomas (GILMS) with the purpose to expand our knowledge on the biological bases of GIST chemo-resistance and to ascertain their significance in patients’ prognosis. P-GP expression was more frequent in GIST than in GI-LMS (83.7% vs. 21.4%, p<0.001), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=0.538). P-GP expression was unrelated to anatomic location (gastric vs. intestinal) in GIST (39/45 vs. 35/43, p=0.770) and in GI-LMS (0/2 vs. 2/6, p=1.000). MT expression was non-significantly higher in GI-LMS than in GIST (35.7% vs. 14.1%, p=0.060), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=1.000). MT expression was unrelated to the anatomic location (gastric vs. intestinal) in GIST (7/45 vs. 6/43) and GI-LMS (0/2 vs. 1/6) (p=1.000 and p=0.1000, respectively). Overall tumor-specific survival (p< 0.001) and disease-free survival (p<0.001) were different in GIST as compared with GI-LMS, and the number of events was higher in GI-LMS. When the survival analysis took into consideration P-GP or MT expression, the overall survival in GIST was influenced by the expression of MT (p=0.021) but not by that of P-GP (p=0.638). However, in GI-LMS, P-GP expression influenced disease-free survival (p=0.050); in addition, it is important to recognize the limited value of these results because of the low number of cases involved in the study. Differential expression of P-GP and MT might explain the known variability in response to systemic chemotherapy in these tumors. Detection of P-GP and MT seems to add certain prognostic value in GIST (MT) or GI-LMS (P-GP).
C1 [Perez-Gutierrez, Sofia] Juan Ramon Jimenez Hospital, Pathology ServiceHuelva, Spain.
[Gonzalez-Campora, Ricardo] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda, Dr. Fedriani s/n, 41009 Seville, Spain.
[Amerigo-Navarro, Joaquin] Hospital Torrecardenas, Pathology ServiceAlmeria, Spain.
[Beato-Moreno, Antonio] University of Seville, Department of Statistic and Operations ResearchSeville, Spain.
[Sanchez-Leon, Maria] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda, Dr. Fedriani s/n, 41009 Seville, Spain.
[Pareja Megia, Maria Jesus] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda, Dr. Fedriani s/n, 41009 Seville, Spain.
[Virizuela-Echaburu, Antonio Juan] Virgen Macarena University Hospital, Oncology ServiceSeville, Spain.
[Lopez-Beltran, Antonio] Reina Sofia University Hospital and Cordoba University Medical School, Department of PathologyCordoba, Spain.
RP Gonzalez-Campora, R (reprint author), Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, 41009 Seville, Spain.
EM rcampora@us.es
CR Berman J, O´Leary TJ: Gastrointestinal stromal tumor workshop. Hum Pathol 32:578-582, 2001.
Dziegiel P, Salwa-Zurawska W, Zurawski J, Wojnar A, Zabel M: Prognostic significance of augmented metallothionein, MT, expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas. Histol Histopathol 2: 83-89, 2005.
Edmonson JH, Marks RS, Buckner JC, Mahoney MR: Contrast of response to dacarbazine, mitomycin, doxorubicin and cisplatin, DMAP, plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest 20:605-612, 2002.
Endresen L, Bakka A, Rugstad HE: Increased resistance to chlorambucil in cultured cells with a high concentration of cytoplasmic metallothionein. 43: 2918-2926, 1983.
Fletcher CMD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW: Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33: 459-465, 2002.
Gaumann A, Tews DS, Mentzel T, Petrow PK, Mayer E, Otto M, Kirkpatrick CJ, Kriegsmann J: Expression of drug resistance related proteins in sarcomas of the pulmonary artery and poorly differentiated leiomyosarcomas of other origin. Virchows Arch 442: 529-537, 2003.
Hegedus T, Orfi L, Seprodi A, Varadi A, Sarkadi B, Keri G: Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1. Biochim Biophys Acta 1587: 318-325, 2002.
Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA: Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumors. J Clin Oncol 21:4342-4349, 2003.
Hirota S, Isozaki K: Pathology of gastrointestinal stromal tumors. Pathol Int 56:1-9, 2006.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279: 577-580, 1998.
Joensuu H, Roberts PJ, Sarlomo-Rikala M Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD: Effect of the tyrosine kinase inhibitor STI571 in a patient with metastatic gastrointestinal stromal tumors. N Engl J Med 344:1052-1056, 2001.
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Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM: Gastrointestinal pacemaker cell tumor, GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259-1269, 1998.
Lehnert T: Gastrointestinal sarcoma, GIST, – a review of surgical management. Ann Chir Gynecol 87: 297-305, 1998.
Merino V, Relevance of multidrug resistance proteins on the clinical efficacy of cancer therapy. 1: 203-212, 2004.
Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG: Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era – a population- based study in western Sweden. Cancer 103: 821-829, 2005.
Ning ZQ, Li J, Arceci RJ: Activating mutation of c-kit at codon 816 confers drug resistance in human leukemia cells. Leuk Lymphoma. 41: 513-522, 2001.
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Theou N, Gil S, Devocelle A Julie C,Lavergne-Slove A, Beauchet A, Callard P, Farinotti R, Le Cesne A, Lemoine A, Faivre-Bonhomme L, Emile JF: Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent expression and initial response to imatinib. Clin Cancer Res 11: 7593-7598, 2005.
Weiss SW, Goldblum JR: Enzinger and Weiss´s soft tissue tumors, 4th ed., Mosby, St. Louis, 2001.
Zwelling A, Slovak ML, Doroshow JH, Hinds M, Chan D, Parker E, Mayes J, Sie KL, Meltzer PS, Trent JM: HT1080/DR4: A P-Glycoprotein-negative human fibrosarcoma cell line exhibiting resistance to topoisomerase II-reactive drugs despite the presence of a drug sensitive topoisomerase II. J Natl Cancer Inst 82: 1553-1561, 1990.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 203
EP 208
PG 6
ER
PT J
AU Bereczki, L
Kis, Gy
Bagdi, E
Krenacs, L
AF Bereczki, Laszlo
Kis, Gyongyi
Bagdi, Eniko
Krenacs, Laszlo
TI Optimization of PCR Amplification for B- and T-cell Clonality Analysis on Formalin-fixed and Paraffin-embedded Samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PCR optimization; B- and T-cell clonality; archived tissues
ID PCR optimization; B- and T-cell clonality; archived tissues
AB In many cases, particularly in retrospective studies, only formalin-fixed and paraffin-embedded (FFPE) tissue samples are available for molecular studies. DNA recovered from FFPE tissues generally consists of fragmented small target sequences with chemical alterations. Clonality analysis is not easy on FFPE samples, in fact, it requires even more experience than that of performed on fresh samples or is more complicated than most genomic PCR amplifications for somatic genes. In our study, we have performed a multi-parameter PCR evaluation investigating immunoglobulin heavy chain gene (IgH) and T-cell receptor gamma gene (TCRgamma) rearrangements on non-purified crude lysates of FFPE samples, in order to establish the significance of different variables on performance of PCR amplification. The results showed that a slight decrease in the concentration of primers in combination with a slight increase in MgCl2 and Taq polymerase concentrations, as well as the use diluted crude template and a standard amount of dNTPs can be the modifications of choice while adjusting IgH and TCRgamma clonality tests on poor quality DNA FFPE samples. Using our improved protocol, 74% (17/23) of the tested B-cell lymphomas and 68% (31/46) of the tested T-cell lymphomas demonstrated monoclonal PCR product, proving the applicability of our optimized method. Our experience may be of help during the optimization process in technically difficult cases as well as to determine which parameters and how should be changed to minimize false-negative and false-positive results.
C1 [Bereczki, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Derkovits fasor 2., H-6726 Szeged, Hungary.
[Kis, Gyongyi] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Derkovits fasor 2., H-6726 Szeged, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Derkovits fasor 2., H-6726 Szeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Derkovits fasor 2., H-6726 Szeged, Hungary.
RP Krenacs, L (reprint author), Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, H-6726 Szeged, Hungary.
EM krenacsl@bay.u-szeged.hu
CR Arnold A, Cossman J, Bakhsi A, et al: Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med 309: 1593-1599, 1983
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Srinivasan M, Sedmak D, Jewell S: Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol 161:1961-1971, 2002
Metz B, Kersten GF, Hoogerhout P, et al: Identification of formaldehyde-induced modifications in proteins. Reactions with model peptides. J Biol Chem 279:6235-6243, 2004
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Sato Y, Sugie R, Tsuchiya B, et al: Comparison of the DNA extraction methods for polymerase chain reaction amplification from formalin- fixed and paraffin-embedded tissues Diagn Mol Pathol 10:265-271, 2001
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Gurbity TP, Bagdi E, Groen NA, et al: Increased sensitivity of Bcell clonality analysis in formalin-fixed and paraffin-embedded Bcell lymphoma samples using an enzyme blend with both 5’->3’ DNA polymerase and 3’->5’ exonuclease activity. Virchows Arch. , 2003
Elenitoba-Johnson KSJ, Bohling SD, Mitchell RS, et al: PCR analysis of the immunoglobulin heavy chain gene in polyclonal processes can yield pseudoclonal bands as an artifact of low B cell number. J Mol Diag 2:92-96, 2000
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 209
EP 214
PG 6
ER
PT J
AU Celikel, C
, E
Gulluoglu, B
Bekiroglu, N
Turhal, S
AF Celikel, Cigdem
, Eren
Gulluoglu, Bahadir
Bekiroglu, Nural
Turhal, Serdar
TI Relation of Neuroendocrine Cells to Transforming Growth Factor-Alpha and Epidermal Growth Factor Receptor Expression in Gastric Adenocarcinomas: Prognostic Implications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE neuroendocrine cells; TGF-alpha; EGFR; gastric carcinoma
ID neuroendocrine cells; TGF-alpha; EGFR; gastric carcinoma
AB The presence of neuroendocrine (NE) cells in gastric adenocarcinoma (GCa) is well documented, however, their significance is controversial. There is no evidence in the literature concerning the possible effect of these cells on the expression of TGF-alpha and EGFR, which are believed to confer growth advantage to tumor cells. 101 partial or total gastrectomy specimens from patients operated for conventional gastric adenocarcinoma were included in the study. In each case immunohistochemistry was performed on sequential tissue sections for chromogranin A (ChrA), TGF-alpha and EGFR. Samples were graded based on the number of ChrA-positive cells (0-3). TGF-alpha and EGFR expressions were evaluated according to both the intensity (0-2) and quantification of the positively stained areas (0-3). Follow-up data was available in 54 patients. Twenty-seven patients died of disease, while 27 patients were alive with a follow-up of at least 15 months. ChrA expression was detected in 54.4% of the tumor specimens. TGF-alpha was stained positively in 42.6% and EGFR in 49.5% of the cases. NE cells in GCa was related to TGF-alpha (p<0.0001) and EGFR expression (p<0.05), and TGF-alpha/EGFR coexpression (p<0.001). Among histopathologic variables, the presence of NE cells was significantly related to grade, stage and lymph node status. Although the presence of NE cells had no effect on survival, the expression of EGFR (p<0.0001) and TGF-alpha (p=0.002) were related to survival. The results of our study suggest that the presence of NE cells may have an effect on the expression of TGF-alpha and EGFR in GCa, and the autocrine mechanism between TGF-alpha and EGFR plays an important role in the prognosis of gastric carcinoma.
C1 [Celikel, Cigdem] Marmara University, School of Medicine, Department of Pathology, Tophanelioglu Cad., 81190 Istanbul, Altunizade, Turkey.
[, Eren] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
[Gulluoglu, Bahadir] Marmara University School of Medicine, Department of BiostatisticsIstanbul, Turkey.
[Bekiroglu, Nural] Marmara University School of Medicine, Department of Medical OncologyIstanbul, Turkey.
[Turhal, Serdar] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
RP Celikel, C (reprint author), Marmara University, School of Medicine, Department of Pathology, 81190 Istanbul, Turkey.
EM turege@superonline.com.tr
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Eren F, Celikel CA, Gulluoglu B: Neuroendocrine differentiation in gastric adenocarcinomas; correlation with tumor stage and expression of VEGF and p53. Pathol Oncol Res 10:47-51, 2004.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 215
EP 226
PG 12
ER
PT J
AU Bovari, J
Czompoly, T
Olasz, K
Hans-Henning, A
Balogh, P
AF Bovari, Judit
Czompoly, Tamas
Olasz, Katinka
Hans-Henning, Arnold
Balogh, Peter
TI Complex Organizational Defects of Fibroblast Architecture in the Mouse Spleen with Nkx2.3 Homeodomain Deficiency
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE spleen; fibroblast heterogeneity; Nkx2.3
ID spleen; fibroblast heterogeneity; Nkx2.3
AB The capacity of secondary lymphoid organs to provide suitable tissue environment for mounting immune responses is dependent on their compartmentalized stromal constituents, including distinct fibroblasts. In addition to various members of the tumor necrosis factor/lymphotoxin beta family as important morphogenic regulators of peripheral lymphoid tissue development, the formation of stromal elements of spleen is also influenced by the Nkx2.3 homeodomain transcription factor in a tissue-specific fashion. Here we extend our previous work on the role of Nkx2.3-mediated regulation in the development of spleen architecture by analyzing the structure of reticular fibroblastic meshwork of spleen in inbred Nkx2.3-deficient mice. Using immunohistochemistry and dual-label immunofluorescence we found both distributional abnormalities, manifested as poor reticular compartmentalization of T-zone and circumferential reticulum, and developmental blockade, resulting in the absence of a complementary fibroblast subpopulation of white pulp. The disregulated distribution of fibroblasts was accompanied with an increased binding of immunohistochemically detectable complement factor C4 by T-cell zone-associated reticular fibroblasts, distinct from follicular dendritic cells with inherently high-level expression of bound C4. These data indicate that the impact of Nkx2.3 gene deficiency on fibroblast ontogeny within the spleen extends beyond its distributional effects, and that the formation of various white pulp fibroblast subsets is differentially affected by the presence of Nkx2.3 activity, possibly also influencing their role in various immune functions linked with complement activation and deposition.
C1 [Bovari, Judit] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7643 Pecs, Hungary.
[Czompoly, Tamas] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7643 Pecs, Hungary.
[Olasz, Katinka] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7643 Pecs, Hungary.
[Hans-Henning, Arnold] Technical University of Braunschweig, Department of Cell & Molecular Biology, Institute of Biochemistry & BiotechnologyBraunschweig, Germany.
[Balogh, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7643 Pecs, Hungary.
RP Balogh, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7643 Pecs, Hungary.
EM peter.balogh@aok.pte.hu
CR Fu YX, Chaplin DD: Development and maturation of secondary lymphoid tissues. Annu Rev Immunol 17: 399-433, 1999.
Mebius RE: Organogenesis of lymphoid tissues. Nat Rev Immunol 3: 292-303, 2003.
Weih F, Caamano J: Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol Rev 195: 91-105, 2003.
Gommerman JL, Browning JL: Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat Rev Immunol 3: 642-655, 2003.
Brendolan A, Ferretti E, Salsi V, Moses K, Quaggin S, Blasi F, Cleary ML, Selleri L: A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Development 132: 3113-3126, 2005.
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Wang CC, Biben C, Robb L, Nassir F, Barnett L, Davidson NO, Koentgen F, Tarlinton D, Harvey RP: Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. Dev Biol 224: 152-167, 2000.
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Balogh P, Balazs M, Czompoly T, Weih DS, Arnold HH, Weih F: Distinct roles of lymphotoxin-beta signaling and the homeodomain transcription factor Nkx2.3 in the ontogeny of endothelial compartments in spleen. Cell Tissue Res 328: 473-486, 2007.
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Lotscher M, Recher M, Hunziker L, Klein MA: Immunologically induced, complement-dependent up-regulation of the prion protein in the mouse spleen: follicular dendritic cells versus capsule and trabeculae. J Immunol 170: 6040-6047, 2003.
Wang SL, Kutche M, DiSciullo G, Schachner M, Bogen SA: Selective malformation of the splenic white pulp border in L1-deficient mice. J Immunol 165: 2465-2473, 2000.
Kraal G, Schornagel K, Streeter PR, Holzmann B, Butcher EC: Expression of the mucosal vascular addressin, MAd- CAM-1, on sinus-lining cells in the spleen. Am J Pathol 147: 763-771, 1995.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 227
EP 235
PG 9
ER
PT J
AU Keresztes, K
Szollosi, Z
Simon, Zs
Tarkanyi, I
Nemes, Z
Illes,
AF Keresztes, Katalin
Szollosi, Zoltan
Simon, Zsofia
Tarkanyi, Ilona
Nemes, Zoltan
Illes, Arpad
TI Retrospective Analysis of the Prognostic Role of Tissue Eosinophil and Mast Cells in Hodgkin's Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hodgkin's lymphoma; mast cell; eosinophil cell
ID Hodgkin's lymphoma; mast cell; eosinophil cell
AB The composition of reactive cell populations, which constitute the majority of tumor load in Hodgkin’s lymphoma (HL), can influence the prognosis of the disease. Besides widely accepted and applied prognostic scores, the authors evaluate biological factors that may have a prognostic impact. Previous data indicate that the rate of eosinophils and mast cells in the reactive cell population, determined already at diagnosis, can be used for this purpose. Histological samples from 104 patients with HL with an average follow-up period of 110 (24-214) months were retrospectively analyzed. Mast cell positivity was associated with better overall survival, although this difference was only of borderline statistical significance (p=0.092). No significant difference was found in parameters like overall survival (OS, p=0.906) or event-free survival (EFS, p=0.307) of eosinophil-positive vs. -negative cases or in EFS (p=0.742) of mast cell-positive vs. -negative individuals (criterion for a positive specimen was more than 5% of appropriate cells in the reactive cell population). Looking at the effect of eosinophilia and mastocytosis together, there was no significant difference between the subgroups categorized according to the combined presence of the two cell types. It seems that tissue eosinophil and mast cell predominance have no prognostic value that could be used in clinical practice, although a tendency for correlation of mast cell positivity with overall survival could be seen. For a definitive statement, multicenter studies should be performed involving a higher number of patients suffering from HL.
C1 [Keresztes, Katalin] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, H-4004 Debrecen, Hungary.
[Szollosi, Zoltan] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Simon, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, H-4004 Debrecen, Hungary.
[Tarkanyi, Ilona] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, H-4004 Debrecen, Hungary.
[Nemes, Zoltan] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, H-4004 Debrecen, Hungary.
RP Keresztes, K (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, H-4004 Debrecen, Hungary.
EM keresztesk@gmail.com
CR Axdorph U, Porwit-MacDonald A, Grimfors G, et al: Tissue eosinophilia in relation to immunopathological and clinical characteristics in Hodgkin’s disease. Leuk Lymphoma 42: 1055-1065, 2001
Costello R, O’Callaghan T, Sebahoun G: Eosinophils and antitumour response. Rev Med Interne 6: 479-484, 2005
d’Amore ES, Lee CK, Aeppli DM, et al: Lack of prognostic value of histopathologic parameters in Hodgkin’s disease, nodular sclerosis type. A study of 123 patients with limited stage disease who had undergone laparotomy and were treated with radiation therapy. Arch Pathol Lab Med 116: 856-861, 1992
Enblad G, Sundstrom C, Glimelius B: Infiltration of eosinophils in Hodgkin’s disease involved lymph nodes predicts prognosis. Hematol Oncol 11: 187-193, 1993
Fischer M, Juremalm M, Olsson N, et al: Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue. Int J Cancer 107: 197-201, 2003
Glimelius I, Edstrom A, Fischer M, et al: Angiogenesis and mast cells in Hodgkin lymphoma. Leukemia 12: 2360-2362, 2005
Hanamoto H, Nakayama T, Miyazato H, et al: Expression of CCL28 by Reed-Sternberg cells defines a major subtype of classical Hodgkin’s disease with frequent infiltration of eosinophils and/or plasma cells. Am J Pathol 164: 997-1006, 2004
Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin’s disease. N Engl J Med 339: 1506-1514, 1998
Hedvat CV, Jaffe ES, Qin J, et al: Macrophage-derived chemokine expression in classical Hodgkin’s lymphoma: application of tissue microarrays. Mod Pathol 12: 1270-1276, 2001
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Jundt F, Anagnostopoulos I, Bommert K, et al: Hodgkin/Reed- Sternberg cells induce fibroblasts to secrete eotaxin, a potent chemoattractant for T cells and eosinophils. Blood 94: 2065- 2071, 1999
Kadin M, Butmarc J, Elovic A, et al: Eosinophils are the major source of transforming growth factor-beta 1 in nodular sclerosing Hodgkin’s disease. Am J Pathol 142: 11-16, 1993
Molin D: Bystander cells and prognosis in Hodgkin lymphoma. Review based on a doctoral thesis. Ups J Med Sci 109: 179- 228, 2004
Molin D, Edstrom A, Glimelius I, et al: Mast cell infiltration correlates with poor prognosis in Hodgkin’s lymphoma. Br J Haematol 119: 122-124, 2002
Molin D, Fischer M, Xiang Z, et al: Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin’s disease. Br J Haematol 114: 616-623, 2001
Mosialos G, Birkenbach M, Yalamanchili R, et al: The Epstein- Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80: 389-399, 1995
Pinto A, Aldinucci D, Gloghini A, et al: Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin’s disease cell line. Blood 88: 3299-3305, 1996
Pinto A, Aldinucci D, Gloghini A, et al: The role of eosinophils in the pathobiology of Hodgkin’s disease. Ann Oncol 8(Suppl 2): 89-96, 1997
Ribatti D, Nico B, Vacca A, et al: Do mast cells help to induce angiogenesis in B-cell non-Hodgkin’s lymphomas? Br J Cancer 77: 1900-1906, 1998
Samoszuk M, Kanakubo E, Chan JK: Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts. BMC Cancer 5: 121, 2005
Samoszuk M, Ramzi E: IgE, Reed-Sternberg cells, and eosinophilia in Hodgkin’s disease. Leuk Lymphoma 9, 315-319, 1993
Skinnider BF, Mak TW: The role of cytokines in classical Hodgkin lymphoma. Blood 99: 4283-4297, 2002
Sorbo J, Jakobsson A, Norrby K: Mast-cell histamine is angiogenic through receptors for histamine 1 and histamine 2. Int J Exp Pathol 75: 43-50, 1994
Teruya-Feldstein J, Jaffe ES, Burd PR, et al: Differential chemokine expression in tissues involved by Hodgkin’s disease: direct correlation of eotaxin expression and tissue eosinophilia. Blood 93: 2463-2470, 1999
Toth J, Dworak O, Sugar J: Eosinophil predominance in Hodgkin’s disease. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 89: 107-111, 1977
von Wasielewski R, Seth S, Franklin J, et al: Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin’s disease, allowing for known prognostic factors. Blood 95: 1207-1213, 2000
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 237
EP 242
PG 6
ER
PT J
AU Maasz, A
Kisfali, P
Horvatovich, K
Mohas, M
Marko, L
Csongei, V
Farago, B
Jaromi, L
Magyari, L
Safrany, E
Sipeky, Cs
Wittmann, I
Melegh, B
AF Maasz, Anita
Kisfali, Peter
Horvatovich, Katalin
Mohas, Marton
Marko, Lajos
Csongei, Veronika
Farago, Bernadett
Jaromi, Luca
Magyari, Lili
Safrany, Eniko
Sipeky, Csilla
Wittmann, Istvan
Melegh, Bela
TI Apolipoprotein A5 T-1131C Variant Confers Risk for Metabolic Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE metabolic syndrome; glucose intolerance; ApoA5; T-1131C
ID metabolic syndrome; glucose intolerance; ApoA5; T-1131C
AB The -1131C is a naturally occurring variant of the apolipoprotein A5 (ApoA5) gene, which has been shown to associate with increased triglyceride levels. This variant has also been shown to confer risk for development of ischemic heart disease and stroke. The gene is in linkage disequilibrium with factors known to correlate with impaired glucose homeostasis. These observations prompted us to study the prevalence of the ApoA5 -1131C allele in patients with metabolic syndrome. A total of 201 metabolic syndrome patients and 210 controls were studied. In both groups the triglyceride levels of patients with -1131C allele were significantly increased compared to the subjects with -1131T allele (3.22+/-0.43 mmol/l vs. 2.24+/-0.12 mmol/l, p<0.01 in the metabolic syndrome patients; 2.10+/-0.19 mmol/l vs. 1.22+/-0.05 mmol/l, p<0.01 in the controls). In metabolic syndrome patients the prevalence of the ApoA5 -1131C variant was increased compared to the healthy controls (11% vs. 6.20%). Multiplex regression analysis model adjusted for age, gender, serum total cholesterol levels, acute myocardial infarction and stroke events revealed that the examined ApoA5 variant confers risk for the development of metabolic syndrome: the odds ratio at 95% confidence interval was 3.622 (1.200-10.936), p=0.02. Our findings strongly suggest that this variant is a risk factor for the development of hypertriglyceridemia and metabolic syndrome.
C1 [Maasz, Anita] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Kisfali, Peter] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Horvatovich, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Mohas, Marton] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Marko, Lajos] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Csongei, Veronika] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Farago, Bernadett] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Jaromi, Luca] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Magyari, Lili] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Safrany, Eniko] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Sipeky, Csilla] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Wittmann, Istvan] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
EM bela.melegh@aok.pte.hu
CR Executive Summary of the Third Report of the National Cholesterol Education Program, NCEP, Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults, Adult Treatment Panel III): JAMA 285:2486-2497, 2001
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Evans D, Buchwald A, Beil FU: The single nucleotide polymorphism -1131T>C in the apolipoprotein A5, APOA5, gene is associated with elevated triglycerides in patients with hyperlipidemia. J Mol Med 81:645-654, 2003
Genoux A, Dehondt H, Helleboid-Chapman A, et al: Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalpha. Arterioscler Thromb Vasc Biol 25:1186-1192, 2005
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Reaven P: Metabolic syndrome. J Insur Med 36:132-142, 2004
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Wright WT, Young IS, Nicholls DP, et al: SNPs at the APOA5 gene account for the strong association with hypertriglyceridaemia at the APOA5/A4/C3/A1 locus on chromosome 11q23 in the Northern Irish population. Atherosclerosis 185:353-360, 2006
Yamada Y, Kato K, Hibino T, et al: Prediction of genetic risk for metabolic syndrome. Atherosclerosis 191:298-304, 2006
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 243
EP 247
PG 5
ER
PT J
AU Bardi, E
Bobok, I
V. Olah, A
Kappelmayer, J
Kiss, Cs
AF Bardi, Edit
Bobok, Ildiko
V. Olah, Anna
Kappelmayer, Janos
Kiss, Csongor
TI Anthracycline Antibiotics Induce Acute Renal Tubular Toxicity in Children with Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE nephrotoxicity; anthracycline therapy; dexrazoxane; NAGi; microalbuminuria
ID nephrotoxicity; anthracycline therapy; dexrazoxane; NAGi; microalbuminuria
AB Experimental evidence suggests that anthracyclines, widely used in cancer chemotherapy, may impair kidney function. We assessed kidney function by serum creatinine, urinary N-acetyl-beta-D-glucosaminidase activity indices (NAGi) and microalbuminuria (MA) in 160 serum and urine samples obtained from 66 children with cancer. The effect of dexrazoxane was analyzed in 6 children on dexrazoxane supportive therapy in conjunction with daunorubicin (DNR) treatment, as compared with 6 children not receiving this agent. NAGi was significantly (p<0.05) elevated after treatment by DNR, doxorubicin, epirubicin (EPI) and idarubicin (IDA). MA proved to be a less sensitive indicator of kidney damage than NAGi. DNR resulted in a progressive deterioration of proximal tubular function as determined by linear regression analysis. The mean NAGi in the dexrazoxanetreated group was significantly (p<0.005) lower than in children not receiving dexrazoxane prior to DNR treatment. In conclusion, our study demonstrated that DNR, EPI and IDA induced an acute renal tubular damage similar to known tubulotoxic agents as cisplatin, carboplatin, cyclophosphamide and ifosfamide. The damage was clinically mild and only a minor proportion of patients can be expected to develop long-lasting tubulopathy with negative impact on the quality of life.
C1 [Bardi, Edit] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei korut, H-4012 Debrecen, Hungary.
[Bobok, Ildiko] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei korut, H-4012 Debrecen, Hungary.
[V. Olah, Anna] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Kappelmayer, Janos] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98. Nagyerdei korut, H-4012 Debrecen, Hungary.
RP Bardi, E (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, H-4012 Debrecen, Hungary.
EM editbardi@hotmail.com
CR Bardi E, Bobok I, Olah VA, et al: Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatr Nephrol 10:1145-1147, 2004
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Kopecna L: Late effects of anticancer therapy on kidney function in children with acute lymphoblastic leukemia. Bratisl Lek Listy 102:357-360, 2001
Kakihara T, Imai C, Uchiyama M, et al: Impaired tubular excretory function as a late side effect of chemotherapy in children. J Pediatr Hematol Oncol 25:209-214, 2003
Bardi E, Olah VA, Bartyik K, et al: Late effects on renal glomerular and tubular function in childhood cancer survivors. Pediatr Blood Cancer 43:668-673, 2004
Schrappe M, Reiter A, Zimmermann M, et al: Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995, Berlin-Frankfurt- Munster. Leukemia 14: 2205-2222, 2000
Creutzig U, Ritter J, Zimmermann M, et al: Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxanthrone: results of Study Acute Myeloid Leukemia-Berlin- Frankfurt-Munster 93. J Clin Oncol 19: 2705-2713, 2001
Reiter A, Schrappe M, Parwaresch R, et al: Non-Hodgkin’s lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage – a report of the Berlin-Frankfurt-Munster Group. J Clin Oncol 13:359-372, 1995
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Marx M, Langer T, Graf N, et al: Multicentre analysis of anthracycline-induced cardiotoxicity in children following treatment according to the nephroblastoma studies SIOP No. 9/ GPOH and SIOP 93-01/ GPOH. Med Pediatr Oncol 39:18-24, 2002
Ozaki T, Flege S, Kevric M, et al: Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 21:334-341, 2003
Koscielniak E, Jurgens H, Winkler K, et al: Treatment of soft tissue sarcoma in childhood and adolescence. A report of the German Cooperative Soft Tissue Sarcoma Study. Cancer 70:2557-2567, 1992
Ninane J, Perilongo G, Stalens JP, et al: Effectiveness and toxicity of cisplatin and doxorubicin, PLADO, in childhood hepatoblastoma and hepatocellular carcinoma: a SIOP pilot study. Med Pediatr Oncol 19:199-203, 1991
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Herman EH, Zhang J, Chadwick DP, Ferrans VJ: Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats. Cancer Chemother Pharmacol 45:329-334, 2000
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 249
EP 253
PG 5
ER
PT J
AU Schiffer, Ch
Schiesser, M
Lehr, J
Tariverdian, G
Glaeser, D
Heinz, G
Mikuz, G
Sergi, C
AF Schiffer, Christiane
Schiesser, Monika
Lehr, Jutta
Tariverdian, Gholamali
Glaeser, Dieter
Heinz, Gabriel
Mikuz, Gregor
Sergi, Consolato
TI Unique Occurrence of Brachmann-de Lange Syndrome in a Fetus whose Mother Presented with a Diffuse Large B-Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
AB Brachmann-De Lange Syndrome (BDLS, MIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by a variable phenotype including intrauterine fetal growth retardation, limb reduction and distinctive facial and skull features (low frontal hairline, synophrys, anteverted nostrils, long philtrum, downturned corners of the mouth, micro- and retrognathia, low-set ears and micro-/brachycephaly), as well as a significant psychological developmental delay. A proposed classification system for BDLS include a classic type with characteristic facial and skull changes, a mild type where similar changes may develop with time or may be partially expressed, and a third type including phenocopies, where phenotypic changes are casually related to chromosomal aneuploidies or teratogenic exposures. We report on a 22-week gestation fetus with BDLS, showing intrauterine fetal growth retardation, brachycephaly, micro-/retrognathia and monolateral single bone of the forearm, in a woman harboring diffuse large B-cell lymphoma. Meticulous family history was negative for malformations, syndromes, congenital anomalies or psychiatric disorders. There are very few reports of BDLS at early gestation, but to the best of our knowledge, this is the first case occurring simultaneously with a hematological neoplastic disease of the mother.
C1 [Schiffer, Christiane] Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental HealthMannheim, Germany.
[Schiesser, Monika] Medical University of Heidelberg, Department of Obstetrics and GynecologyHeidelberg, Germany.
[Lehr, Jutta] Medical University of Heidelberg, Department of Obstetrics and GynecologyHeidelberg, Germany.
[Tariverdian, Gholamali] Medical University of Heidelberg, Department of Clinical GeneticsHeidelberg, Germany.
[Glaeser, Dieter] Center of Human Genetics, Gregor Mendel LaboratoriesNeu-Ulm, Germany.
[Heinz, Gabriel] Center of Medical GeneticsOsnabrueck, Germany.
[Mikuz, Gregor] Medical University of Innsbruck, Department of Pathology, Muellerstrasse 44, A-6020 Innsbruck, Austria.
[Sergi, Consolato] Medical University of Innsbruck, Department of Pathology, Muellerstrasse 44, A-6020 Innsbruck, Austria.
RP Sergi, C (reprint author), Medical University of Innsbruck, Department of Pathology, A-6020 Innsbruck, Austria.
EM consolato.sergi@i-med.ac.at
CR Aitken DA, Ireland M, Berry E, Crossley JA, Macri JN, Burn J, Connor JM: Second-trimester pregnancy associated plasma protein-A levels are reduced in Cornelia de Lange syndrome pregnancies. Prenat Diagn 19: 706-710, 1999
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De Die-Smulders C, Theunissen P, Schrander-Stumpel C, Frijns JP: On the variable expression of the Brachmann-de Lange syndrome. Clin Genet 41: 42-45, 1992
Ireland M, Donnai D, Burn J: Brachmann-de Lange syndrome. Delineation of the clinical phenotype. Am J Med Genet 47: 959-964, 1993
Jackson L, Kline AD, Barr MA, Koch S: De Lange syndrome: a clinical review of 310 individuals. Am J Med Genet 47: 940- 946, 1993
Kliewer MA, Kahler SG, Hertzberg BS, Bowie JD: Fetal biometry in the Brachmann-de Lange syndrome. Am J Med Genet 47: 1035-1041, 1993
Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG: Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet 36: 631-635, 2004
Lakshminarayana P, Nallasivam P: Cornelia de Lange syndrome with ring chromosome 3. J Med Genet 27: 405-406, 1990
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Nowaczyk MJ, Mohide P: Brachmann-de Lange Syndrome. McMaster University Prenatal Diagnosis Rounds. Front Fet Heath 2001; 3, www.sickkids.on.ca)
Pajkrt E, Weisz B, Firth HV, Chitty LS: Fetal cardiac anomalies and genetic syndromes. Prenat Diagn 24: 1104-1115, 2004
Pilu G, Nicolaides KH: Diagnosis of fetal abnormalities. The 18-23-week scan. Parthenon Publishing, New York, NY, 1999
Ranzini AC, Day-Salvatore D, Farren-Chavez D, McLean DA, Greco R: Prenatal diagnosis of de Lange syndrome. J Ultrasound Med 16: 755-758, 1997
Sekimoto H, Osada H, Kimura H, Kamiyama M, Arai K, Sekiya S: Prenatal findings in Brachmann-de Lange syndrome. Arch Gynecol Obstet 263: 182-184, 2000
Sugita K, Izumi T, Yamaguchi K, Fukuyama Y, Sato A, Kajita A: Cornelia de Lange syndrome associated with a suprasellar germinoma. Brain Dev 8: 541-546, 1986
Tonkin ET, Wang TJ, Lisgo S, Bamshad MJ, Strachan T: NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat Genet 36: 636-641, 2004
Urban M, Hartung J: Ultrasonographic and clinical appearance of a 22-week-old fetus with Brachmann-de Lange syndrome. Am J Med Genet 102: 73-75, 2001
Van Allen MI, Filippi G, Siegel-Bartelt J, Yong SL, McGillivray B, Zuker RM, Smith CR, Magee Jf, Ritchie S, Toi A, Reynolds JF: Clinical variability within Brachmann-de Lange syndrome: a proposed classification system. Am J Med Genet 47: 947- 958, 1993
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 255
EP 259
PG 5
ER
PT J
AU Szomor,
Al Saati, T
Delsol, G
Kereskai, L
Szijarto, Zs
Losonczy, H
AF Szomor, Arpad
Al Saati, Talal
Delsol, Georges
Kereskai, Laszlo
Szijarto, Zsuzsanna
Losonczy, Hajna
TI Primary Bone Marrow T-cell Anaplastic Large Cell Lymphoma with Triple M Gradient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE anaplastic large cell lymphoma; T-cell receptor gene rearrangement; immunoglobulin heavy chain gene rearrangement; M gradient; bone marrow
ID anaplastic large cell lymphoma; T-cell receptor gene rearrangement; immunoglobulin heavy chain gene rearrangement; M gradient; bone marrow
AB We present a case of a 60-year-old male patient with primary bone marrow anaplastic large cell lymphoma. He was admitted to the hospital with the symptoms of anemia and fever. There was no evidence of lymphadenopathy or splenomegaly. Immunoelectrophoresis showed the presence of a triple M gradient (double IgM and an IgG), with the IgG and one of the IgM paraproteins functioning as a cryoglobulin. The patient had no hepatitis C virus infection. Bone marrow biopsy showed massive CD30-positive, ALK-negative large lymphoid cell infiltration of T-cell origin with anaplastic morphology. PCR analysis of lymphoid cells separated from the bone marrow demonstrated the presence of a B/T hybrid genotype disorder with no evidence of the t(2;5), nor t(1;2) translocations. The patient entered a period of remission following CHOP chemotherapy. The patient subsequently died of sepsis as a consequence of serious humoral immunodeficiency.
C1 [Szomor, Arpad] University of Pecs, I. Department of Internal Medicine, Ifjusag u. 13., H-7624 Pecs, Hungary.
[Al Saati, Talal] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Delsol, Georges] Central Hospital University Purpan, Laboratory of Anatomic PathologyToulouse, France.
[Kereskai, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Szijarto, Zsuzsanna] University of Pecs, Department of OphthalmologyPecs, Hungary.
[Losonczy, Hajna] University of Pecs, I. Department of Internal Medicine, Ifjusag u. 13., H-7624 Pecs, Hungary.
RP Szomor, (reprint author), University of Pecs, I. Department of Internal Medicine, H-7624 Pecs, Hungary.
EM aszomor@clinics.pote.hu
CR Falini B, Pileri S, Zinzani PL, Carbone A, Zagonel V, Wolf- Peters CD, Verhoef G, Manestrina F, Tedeschini G, Paulli M, Lazzarino M, Giardini R, Aiello A, Foss HD, Araujo I, Fizzotti M, Pelicci PG, Flenghi L, Martelli MF, Santucci A: ALK+ lymphoma: clinico-pathological findings and outcome. Blood 93: 2697-2706, 1999
Garcia MJ, Martinez-Delgado B, Granizo JJ, Benitez J, Rivas C: IgH, TCR-gamma, and TCR-beta gene rearrangement in 80 B- and T-cell non-Hodgkin’s lymphomas: study of the associations between proliferation and so-called „aberrant” patterns. Diagn Mol Pathol 10: 69-77, 2001
Greer JP, Kinney MC, Collins RD, Salhany KE, Wolff SN, Hainsworth JD, Flexner JM, Stein RS: Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol 9: 539-547, 1991
Lamant L, Meggetto F, Al Saati T, Brugieres L, Paillerets BB, Dastugue N, Bernheim A, Rubie H, Terrier-Lacombe J, Robert A, Brousset P, Rigal F, Schlaifer D, Shiota M, Mori S, Delsol G: High incidence of the t(2;5)(p23;q35, translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin’s disease. Comparison of cytogenetic analysis, reverse transcriptase- polymerase chain reaction, and P-80 immunostaining. Blood 87: 284-291, 1996
Longo G, Federico M, Pieresca C, Avanzini P, Iannito E, Di Prisco AU, Baldini L, Brugiatelli M, Clo V, Bevini M, Silingardi V: Anaplastic large cell lymphoma, CD30+/Ki-1+). Analysis of 35 cases followed at GISL centres. Eur J Cancer 31A: 1763-1767, 1995
Shulman LN, Frisard N, Antin JH, Wheeler C, Pinkus G, Magauran N, Mauch P, Nobles E, Mashal R, Canellos G, Tung N, Kadin M: Primary Ki-1 anaplastic large-cell lymphoma in adults: clinical characteristics and therapeutic outcome. J Clin Oncol 11: 937-942, 1993
Stein H, Foss HD, Durkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B: CD30+ anaplastic large cell lymphoma: a review of its histopathologic, genetic and clinical features. Blood 96: 3681-3695, 2000
Szomor A, Molnar L, Ivanyi J, Radvanyi G, Nagy Z, Karadi A, Gergely L, Banyai A, Demeter J, Aryan H, Gasztonyi Z, Kiss A, Kollar B, Egyed M, Losonczy H, Kelenyi G, Pajor L: Extranodal involvement in primary systemic anaplastic large cell lymphoma, ALCL, in adults. Ann Hematol 80: B144-145, 2001
Theriault C, Galoin S, Valmary S, Selves J, Lamant L, Roda D, Rigal-Huguet F, Brousset P, Delsol G, Al Saati T: PCR analysis of immunoglobulin heavy chain, IgH, and TcR-gamma chain rearrangements in the diagnosis of lymphoproliferative disorders of a study of 525 cases. Mod Pathol 13: 1269-1279, 2000
Tilly H, Gaulard P, Lepage E, Dumontet C, Diebold J, Plantier I, Berger F, Symann M, Pertella T, Lederlin P, Briere J: Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome. Blood 90: 3727-3734, 1997
Zinzani PL, Bendandi M, Martelli M, Falini B, Sabattini E, Amadori S, Gherlinzoni F, Martelli MF, Mandelli F, Tura S, Pileri SA: Anaplastic large-cell lymphoma: prognostic evaluation of 90 adult patients. J Clin Oncol 14: 955-962, 1996
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2007
VL 13
IS 3
BP 260
EP 262
PG 3
ER
PT J
AU Tornoczky, T
Semjen, D
Shimada, H
Ambros, MI
AF Tornoczky, Tamas
Semjen, David
Shimada, Hiroyuki
Ambros, M Inge
TI Pathology of Peripheral Neuroblastic Tumors: Significance of Prominent Nucleoli in Undifferentiated/Poorly Differentiated Neuroblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE LCN; LNN; neuroblastoma; nucleoli; INPC; MYCN; amplification; ganglion cell; maturation; Schwann cell
ID LCN; LNN; neuroblastoma; nucleoli; INPC; MYCN; amplification; ganglion cell; maturation; Schwann cell
AB The presence of large cells having simultaneously increased cytoplasmic and nuclear volume accompanied by prominent nucleoli; i.e., differentiating neuroblasts and ganglion cells, is well documented in peripheral neuroblastic tumors (pNTs), and considered as one of the signs of tumor maturation and an indication of a better prognosis of the patients. On the other hand, in 2004 it was reported that large-cell neuroblastoma composed of neuroblastic cells with only nuclear enlargement without recognizable cytoplasmic maturation behaved poorly clinically. Here we are proposing a new pNT subtype in the neuroblastoma category, in addition to the undifferentiated, poorly differentiated and differentiating subtypes: that is large nucleolar neuroblastoma (LNN) characterized by large prominent nucleoli and no or very little amount of discernible cytoplasm. LNN, whose neuroblastic cells are often large in size due to nuclear enlargement, includes those tumors previously categorized into the large-cell neuroblastoma group. LNN tumors, regardless of the size of nuclei, seem to behave aggressively with a very poor prognosis of the patients. It is speculated that nucleolar enlargement without cytoplasmic maturation in LNN tumor cells can be a sign of MYCN amplification.
C1 [Tornoczky, Tamas] University of Pecs, Department of Pathology, Szigeti ut 12., H-7643 Pecs, Hungary.
[Semjen, David] University of Pecs, Department of Pathology, Szigeti ut 12., H-7643 Pecs, Hungary.
[Shimada, Hiroyuki] University of Southern California, Keck Medical Center, Department of PathologyLos Angeles, CA, USA.
[Ambros, M Inge] St. Anna Kinderkrebsforschung, Children’s Cancer Research InstituteVienna, Austria.
RP Tornoczky, T (reprint author), University of Pecs, Department of Pathology, H-7643 Pecs, Hungary.
EM ttamas64@hotmail.com
CR Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B: Terminology and morphologic criteria of neuroblastic tumors. Recommendations by the International Neuroblastoma Pathology Committee. Cancer 86: 349-363, 1999
Peuchmaur M, d’Amore ES, Joshi VV, Roald B, Dehner LP, Gerbing RB, Stram DO, Lukens JN, Matthay KK. Shimada H: Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular. Cancer 98:2274-2281, 2003
Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, Stram DO, Gerbing RB, Lukens JN, Matthay KK, Castleberry RP: International Neuroblastoma Pathology Classification, the Shimada System). Cancer 86: 364-372, 1999
Shimada H, Umehara S, Monobe Y, Hachitanda Y, Nakagawa A, Goto S, Gerbing RB, Stram DO, Lukens JN, Matthay KK: International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors. A report from the Children’s Cancer Group. Cancer 92:2451- 2461, 2001
Shimada H, Chatten J, Newton WA Jr., Sachs N, Hamoudi AB, Chiba T, Marsden HB, Misugi K: Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst 73:405-416, 1984
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Kobayashi C, Monforte-Munoz HL, Gerbing RB, Stram DO, Matthay KK, Lukens JN, Seeger RC, Shimada H: Enlarged and prominent nucleoli may be indicative of MYCN amplification. Cancer 103:174-180, 2005
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 269
EP 275
PG 7
ER
PT J
AU Grant, GS
Das, R
Cerceo, MCh
Rubinstein, SW
Latimer, JJ
AF Grant, G Stephen
Das, Rubina
Cerceo, M Christina
Rubinstein, S Wendy
Latimer, J Jean
TI Elevated Levels of Somatic Mutation in a Manifesting BRCA1 Mutation Carrier
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE somatic mutation; hypoxanthine-guanine phosphoribosyl transferase; glycophorin A; BRCA1 gene; inherited breast cancer syndrome; Fanconi anemia; xeroderma pigmentosum
ID somatic mutation; hypoxanthine-guanine phosphoribosyl transferase; glycophorin A; BRCA1 gene; inherited breast cancer syndrome; Fanconi anemia; xeroderma pigmentosum
AB Homozygous loss of activity at the breast cancerpredisposing genes BRCA1 and BRCA2 (FANCD1) confers increased susceptibility to DNA double strand breaks, but this genotype occurs only in the tumor itself, following loss of heterozygosity at one of these loci. Thus, if these genes play a role in tumor etiology as opposed to tumor progression, they must manifest a heterozygous phenotype at the cellular level. To investigate the potential consequences of somatic heterozygosity for a BRCA1 mutation demonstrably associated with breast carcinogenesis on background somatic mutational burden, we applied the two standard assays of in vivo human somatic mutation to blood samples from a manifesting carrier of the Q1200X mutation in BRCA1 whose tumor was uniquely ascertained through an MRI screening study. The patient had an allele-loss mutation frequency of 19.4 x 10-6 at the autosomal GPA locus in erythrocytes and 17.1 x 10-6 at the X-linked HPRT locus in lymphocytes. Both of these mutation frequencies are significantly higher than expected from age-matched disease-free controls (P < 0.05). Mutation at the HPRT locus was similarly elevated in lymphoblastoid cell lines established from three other BRCA1 mutation carriers with breast cancer. Our patient’s GPA mutation frequency is below the level established for diagnosis of homozygous Fanconi anemia patients, but consistent with data from obligate heterozygotes. The increased HPRT mutation frequency is more reminiscent of data from patients with xeroderma pigmentosum, a disease characterized by UV sensitivity and deficiency in the nucleotide excision pathway of DNA repair. Therefore, this BRCA1-associated breast cancer patient manifests a unique phenotype of increased background mutagenesis that likely contributed to the development of her disease independent of loss of heterozygosity at the susceptibility locus.
C1 [Grant, G Stephen] Graduate School of Public Health, Department of Environmental and Occupational HealthPittsburgh, PA, USA.
[Das, Rubina] Graduate School of Public Health, Department of Environmental and Occupational HealthPittsburgh, PA, USA.
[Cerceo, M Christina] Graduate School of Public Health, Department of Environmental and Occupational HealthPittsburgh, PA, USA.
[Rubinstein, S Wendy] Northwestern University Feinberg School of Medicine, Department of MedicineChicago, IL, USA.
[Latimer, J Jean] University of Pittsburgh, School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences and Magee Womens Research InstitutePittsburgh, PA, USA.
RP Grant, GS (reprint author), Graduate School of Public Health, Department of Environmental and Occupational Health, Pittsburgh, USA.
EM grantsg@upmc.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 276
EP 283
PG 8
ER
PT J
AU Jin, PS
Kim, HJ
Kim, AM
Yang, HK
Lee, EH
Lee, SH
Kim, HW
AF Jin, Pil Seon
Kim, Hun Ji
Kim, A Min
Yang, Han-Kwang
Lee, Eun Hee
Lee, Seung Hye
Kim, Ho Woo
TI Prognostic Significance of Loss of c-Fos Protein in Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE stomach neoplasms; immunohistochemistry; survival analysis; proto-oncogene protein c-fos; tumor suppressor protein; tissue array analysis
ID stomach neoplasms; immunohistochemistry; survival analysis; proto-oncogene protein c-fos; tumor suppressor protein; tissue array analysis
AB c-fos was first identified as a viral oncoprotein, and has been studied in terms of its oncogenic function in tumorigenesis. Many experimental and clinical data indicated that c-fos expression plays a role in the progression of several types of carcinomas. However, some recent studies challenge this view as they indicate that c-fos has tumor suppressor activity. In the present study, we assessed c-fos protein expression in 625 consecutive gastric cancers immunohistochemically, and analyzed its relationship with clinicopathologic factors and survival. We found that a loss of c-fos expression is correlated with a more advanced stage, lymph node metastasis, lymphatic invasion and shorter survival, indicating that c-fos expression in gastric cancer cells is lost during progression and that this loss is associated with a poor prognosis. The above findings suggest that loss of c-fos expression has tumor suppressor activity in gastric cancer and we suspect that this suppressor activity might be related to the pro-apoptotic function of c-fos.
C1 [Jin, Pil Seon] Seoul National University College of Medicine, Department of Pathology, 28 Yeongeon-dong, 110-799 Seoul, South Korea.
[Kim, Hun Ji] Seoul National University College of Medicine, Cancer Research InstituteSeoul, South Korea.
[Kim, A Min] Seoul National University College of Medicine, Department of Pathology, 28 Yeongeon-dong, 110-799 Seoul, South Korea.
[Yang, Han-Kwang] Seoul National University College of Medicine, Department of SurgerySeoul, South Korea.
[Lee, Eun Hee] Seoul National University Bundang Hospital, Department of PathologySeongnam, South Korea.
[Lee, Seung Hye] Seoul National University Bundang Hospital, Department of PathologySeongnam, South Korea.
[Kim, Ho Woo] Seoul National University College of Medicine, Department of Pathology, 28 Yeongeon-dong, 110-799 Seoul, South Korea.
RP Kim, HW (reprint author), Seoul National University College of Medicine, Department of Pathology, 110-799 Seoul, South Korea.
EM woohokim@snu.ac.kr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 284
EP 289
PG 6
ER
PT J
AU Deligezer, U
Dalay, N
AF Deligezer, Ugur
Dalay, Nejat
TI Expression of the TRAIL Receptors in Blood Mononuclear Cells in Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TRAIL receptors; expression; circulating tumor cells; translocation
ID TRAIL receptors; expression; circulating tumor cells; translocation
AB TRAIL receptors are differentially expressed on restricted subpopulations of normal blood cells. In the present study, we investigated the utility of individual TRAIL receptors in evaluating the presence of circulating tumor cells in blood. Patients with chronic myeloid leukemia (CML) carrying the t(9;22) translocation were compared with patients in whom no translocation was detected, with patients with multiple myeloma and with a group of healthy individuals. TRAIL receptor expression was analyzed by RT-PCR in blood mononuclear cells. Blood mononuclear cells of healthy subjects expressed the TRAIL-R1 and TRAIL-R2 death receptors and the TRAIL-R4 decoy receptor while the other decoy receptor TRAIL-R3 was not detectable. This normal expression pattern was also observed in all cases with multiple myeloma and in almost all patients without translocation (42/43; 97.7%). However, in 24/56 (42.9%) of the translocation-positive patients, the expression pattern was completely different. In this group the TRAIL-R4 receptor alone or in combination with TRAIL-R1 disappeared from blood mononuclear cells, while the TRAIL-R2 was expressed at normal level, indicating that the loss of expression is specific for the TRAIL-R4 and TRAIL-R1. This expression pattern was also confirmed by real-time PCR. The differences between the translocation-positive and -negative groups for the TRAIL-R4 and TRAIL-R1 expression were highly significant (p=0.0001 and p=0.0004, respectively). However, the differential expression pattern did not correlate with the number of leukemic cells. Our results suggest a correlation between the presence of leukemic cells in circulation and the differential expression pattern of TRAIL receptors in blood mononuclear cells.
C1 [Deligezer, Ugur] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
[Dalay, Nejat] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
RP Dalay, N (reprint author), Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34390 Istanbul, Turkey.
EM ndalay@yahoo.com
CR Fiorucci G, Vannucchi S, Chiantore MV, et al: TNF-related apoptosis- inducing ligand, TRAIL, as a pro-apoptotic signal transducer with cancer therapeutic potential. Curr Pharm Des 11:933-944, 2005
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 290
EP 294
PG 5
ER
PT J
AU Felber, M
Sonnemann, J
Beck, FJ
AF Felber, Matthias
Sonnemann, Jurgen
Beck, F James
TI Inhibition of Novel Protein Kinase C-epsilon Augments TRAIL-induced Cell Death in A549 Lung Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; medulloblastoma; NPC 15437; protein kinase C-epsilon; TNF; TRAIL
ID lung cancer; medulloblastoma; NPC 15437; protein kinase C-epsilon; TNF; TRAIL
AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has great potential for cancer treatment since it provokes cell death in most tumor cells while leaving most normal cells unscathed. Some cancers, however, show resistance to TRAIL, indicating that TRAIL alone may be insufficient for cancer therapy. Here we studied whether the apoptotic susceptibility of A549 non-small cell lung cancer cells could be modulated by inhibiting protein kinase C (PKC). We show that an inhibitor with preference for novel PKC isozymes, NPC 15437, significantly augmented TRAIL sensitivity of A549 cells, as judged by assessing cell death and mitochondrial membrane potential. Likewise, NPC 15437 also significantly potentiated the responsiveness of DAOY medulloblastoma cells to TRAIL. In contrast, an inhibitor with preference for conventional PKC isozymes, Go6976, did not augment TRAIL sensitivity of A549 cells. To further specify the PKC isozyme responsible for TRAIL sensitization, we used a peptide inhibitor with selectivity for the novel PKC isozyme epsilon, myr-PKC-epsilon V1-2. The inhibition of PKC-epsilon resulted in a significant amplification of the cytotoxic activity of TRAIL in A549 cells. Altogether, our study provides evidence for a considerable role of PKC-epsilon in the apoptotic responsiveness of A549 lung cancer cells, and possibly other malignancies, to TRAIL.
C1 [Felber, Matthias] Ernst Moritz Arndt University, Research Center of Pharmacology and Experimental TherapeuticsGreifswald, Germany.
[Sonnemann, Jurgen] Ernst Moritz Arndt University, Research Center of Pharmacology and Experimental TherapeuticsGreifswald, Germany.
[Beck, F James] Ernst Moritz Arndt University, Department of Pediatric Oncology/Hematology, Soldmannstr. 15, D-17475 Greifswald, Germany.
RP Beck, FJ (reprint author), Ernst Moritz Arndt University, Department of Pediatric Oncology/Hematology, D-17475 Greifswald, Germany.
EM beck@uni-greifswald.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 295
EP 301
PG 7
ER
PT J
AU Hajdu, M
Luttun, A
Pelacho, B
Burns, CT
Chase, L
Gutierrez-Perez, M
Jiang, Y
Lenvik, T
Vas, V
Uher, F
Sebestyen, A
Verfaillie, C
AF Hajdu, Melinda
Luttun, Aernout
Pelacho, Beatriz
Burns, C Terry
Chase, Lucas
Gutierrez-Perez, Maria
Jiang, Yuehua
Lenvik, Todd
Vas, Virag
Uher, Ferenc
Sebestyen, Anna
Verfaillie, Catherine
TI Transcriptional Characterization of the Notch Signaling Pathway in Rodent Multipotent Adult Progenitor Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Notch; HES-1; multipotent adult progenitor cell; stem cell
ID Notch; HES-1; multipotent adult progenitor cell; stem cell
AB The Notch signaling pathway is a multifunctional, evolutionarily conserved pathway, which plays an important role in development as well as stem cell biology. Multipotent adult progenitor cells (MAPCs) represent a unique stem cell population, which is capable of differentiating into cell types of the ectodermal, mesodermal and endodermal lineages in vitro, and contribute to most somatic cell types in vivo. Our aim was to characterize the gene expression of Notch signaling elements in rodent MAPCs. We show that transcripts for Notch-receptors, ligands, regulatory molecules of the pathway and the Hairy/Enhancer of Split-1 (HES-1) target gene are present in mouse and rat low-Oct4 MAPCs. We found that mouse Notch3 and rat Notch1 transcripts increased when cells were cultured at high density for 48 to 96 hours. HES-1 and HES-related transcription factor-1 (HERP-1), transcriptional targets of Notch-signaling, were both elicited by immobilized Delta1 ligand. In addition, mRNA for Notch1 and Notch3 was also induced by Notch-signaling, suggesting the presence of regulatory feedback loops. Slight differences between mouse and rat derived MAPCs suggest that the exact function, transcriptional regulation and the fine-tuning of the signal may be species specific. Taken together, we characterized the gene expression profile of the Notch pathway in rodent low-Oct4-MAPCs, and showed that the pathway is functional and can be modulated. Our results provide an additional tool and a further basis for a better understanding of stem cell biology.
C1 [Hajdu, Melinda] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Luttun, Aernout] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Pelacho, Beatriz] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Burns, C Terry] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Chase, Lucas] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Gutierrez-Perez, Maria] University of Navarra, Hematology and Cell Therapy, Clinica UniversitariaPamplona, Spain.
[Jiang, Yuehua] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Lenvik, Todd] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
[Vas, Virag] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Uher, Ferenc] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., H-1085 Budapest, Hungary.
[Verfaillie, Catherine] University of Minnesota Medical School, Stem Cell InstituteMinneapolis, MN, USA.
RP Hajdu, M (reprint author), University of Minnesota Medical School, Stem Cell Institute, Minneapolis, USA.
EM melindahajdu@freemail.hu
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Walker L, Lynch M, Silverman S, Fraser J, Boulter J, Weinmaster G, Gasson JC: The Notch/Jagged Pathway Inhibits Proliferation of Human Hematopoietic Progenitors In Vitro. Stem Cells 17: 162-171, 1999.
Lanner F, Sohl M, Farnebo F: Functional arterial and venous fate is determined by graded VEGF signaling and notch status during embryonic stem cell differentiation. Arterioscler Thromb Vasc Biol 27: 487-493, 2007.
Gruen L, Grabel L: Concise review: scientific and ethical roadblocks to human embryonic stem cell therapy. Stem Cells 24: 2162-2169, 2006.
Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima Y, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C: Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 113: 1701-1710, 2004.
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM: Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98: 2615-2625, 2001.
Jiang Y, Jahargirdar BN, Reinhardt RL, Schwartz RE, Keene, CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41-49, 2002.
Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM: Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30: 896-904, 2002.
Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM: Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109: 1291-1302, 2002.
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Breyer A, Estharabadi N, Oki M, Ulloa F, Nelson-Holte M, Lien L, Jian Y: Multipotent adult progenitor cell isolation and culture procedures. Exp Hematol 34: 1596-1601, 2006.
Ulloa-Montoya F, Kidder BL, Pauwelyn KA, Chase LG, Luttun A, Crabbe A, Geraerts M, Sharov AA, Piao Y, Ko MS, Hu WS, Verfaillie CM: Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity. Genome Biol 6: R163, 2007.
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Carlson ME, Conboy IM: Regulating the Notch pathway in embryonic, adult and old stem cells. Current Opinion Pharmacol 7: 1-7, 2007.
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Neves H, Weerkamp F, Gomes AC, Naber BAE, Gameiro P, Becker JD, Lucio P, Clode N, van Dongen JJM, Staal FJT, Parreira L: Effects of Delta1 and Jagged1 on Early Human Hematopoiesis: Correlation with Expression of Notch Signaling- Related Genes in CD34+ Cells. Stem Cells 24: 1328- 1337, 2006.
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Yu X, Alder JK, Chun JH, Friedman AD, Heimfeld S, Cheng L, Civin CI: HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem Cells 24: 876-888, 2006.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 302
EP 310
PG 9
ER
PT J
AU Varga, G
Kiss, J
Varkonyi, J
Vas, V
Farkas, P
Paloczi, K
Uher, F
AF Varga, Gergely
Kiss, Judit
Varkonyi, Judit
Vas, Virag
Farkas, Peter
Paloczi, Katalin
Uher, Ferenc
TI Inappropriate Notch Activity and Limited Mesenchymal Stem Cell Plasticity in the Bone Marrow of Patients with Myelodysplastic Syndromes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cobblestone area-forming cells; Jagged-1; myelodysplastic syndromes; Notch signaling; stem cell plasticity
ID cobblestone area-forming cells; Jagged-1; myelodysplastic syndromes; Notch signaling; stem cell plasticity
AB Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematological disorders characterized by ineffective hematopoiesis, enhanced bone marrow apoptosis and frequent progression to acute myeloid leukemia. Several recent studies suggested that, besides the abnormal development of stem cells, microenvironmental alterations are also present in the MDS bone marrow. In this study, we have examined the relative frequencies of stem and progenitor cell subsets of MDS and normal hematopoietic cells growing on stromal cell layers established from MDS patients and from normal donors. When hematopoietic cells from MDS patients were co-cultured with normal stromal cells, the frequency of either early or late cobblestone area-forming cells (CAFC) was significantly lower compared to the corresponding normal control values in 4 out of 8 patients. In the opposite situation, when normal hematopoietic cells were incubated on MDS stromal cells, the CAFC frequencies were decreased in 5 out of 6 patients, compared to normal stromal layer-containing control cultures. Moreover, a soluble Notch ligand (Jagged-1 protein) was an inhibitor of day-35-42 CAFC when normal hematopoietic cells were cultured with normal or MDS stromal cells, but was unable to inhibit MDS stem and early progenitor cell growth (day-35-42 CAFC) on pre-established stromal layers. These findings suggest that in early hematopoietic cells isolated from MDS patients the Notch signal transduction pathway is disrupted. Furthermore, there was a marked reduction in the plasticity of mesenchymal stem cells of MDS patients compared with those of normal marrow donors, in neurogenic and adipogenic differentiation ability and hematopoiesis supporting capacity in vitro. These results are consistent with the hypothesis that when alterations are present in the myelodysplastic stroma environment along with intrinsic changes in a hematopoietic stem/progenitor cell clone, both factors might equally contribute to the abnormal hematopoiesis in MDS.
C1 [Varga, Gergely] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Kiss, Judit] National Medical Center, Department of Hematology and Stem Cell Transplantation, Dioszegi ut 64., H-1113 Budapest, Hungary.
[Varkonyi, Judit] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Vas, Virag] National Medical Center, Department of Hematology and Stem Cell Transplantation, Dioszegi ut 64., H-1113 Budapest, Hungary.
[Farkas, Peter] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Paloczi, Katalin] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Uher, Ferenc] National Medical Center, Department of Hematology and Stem Cell Transplantation, Dioszegi ut 64., H-1113 Budapest, Hungary.
RP Uher, F (reprint author), National Medical Center, Department of Hematology and Stem Cell Transplantation, H-1113 Budapest, Hungary.
EM uher@kkk.org.hu
CR Aizawa S, Nakano M, Iwase O, et al: Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro. Leuk Res 23: 239-246, 1999
Alvi S, Shaher A, Shetty V, et al: Successful establishment of long-term bone marrow cultures in 103 patients with myelodysplastic syndromes. Leuk Res 25: 941-954, 2001
Artavanis-Tsakonas S, Rand MD, Lake RJ: Notch signaling: cell fate control and signal integration in development. Science 284: 770-776, 1999
Baldron V, Ruiz-Hidalgo MJ, Nueda ML, et al: Dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats. Exp Cell Res 303: 343-359, 2005
Borojevic R, Roela RA, Rodarte RS, et al: Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression. Leuk Res 28: 831-844, 2004
Breems DA, Blokland EAW, Neben S, Ploemacher RE: Frequency analysis of human primitive haematopoietic stem cell subsets using a cobblestone area forming cell assay. Leukemia 8: 1095-1104, 1994
Coutinho LH, Geary CG, Chang J, et al: Functional studies of bone marrow haematopoietic and stromal cells in the myelodysplastic syndrome, MDS). Br J Haematol 75: 16-25, 1990
Flores-Figueroa E, Arana-Trejo RM, Gutierrez-Espindola G, et al: Mesenchymal stem cells in myelodysplastic syndromes: phenotypic and cytogenetic characterization. Leuk Res 29: 215-224, 2005
Flores-Figueroa E, Gutierrez-Espindola G, Montesinos JJ, et al: In vitro characterization of hematopoietic microenvironment cells from patients with myelodysplastic syndrome. Leuk Res 26: 677-686, 2002
Hofmann W-K, de Vos S, Komor M, et al: Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood 100: 3553-3560, 2002
Jones P, May G, Healy L, et al: Stromal expression of Jagged 1 promotes colony formation by fetal hematopoietic progenitor cells. Blood 92: 1505-1511, 1998
Karanu FN, Murdoch B, Gallacher L, et al: The Notch ligand Jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med 192: 1365-1372, 2000
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 311
EP 319
PG 9
ER
PT J
AU Yuan, A
Liu, J
Liu, Y
Cui, G
AF Yuan, Aping
Liu, Jinzhong
Liu, Yiqing
Cui, Guanglin
TI Chromogranin A-Positive Tumor Cells in Human Esophageal Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE esophagus; squamous cell carcinoma; neuroendocrine; differentiation
ID esophagus; squamous cell carcinoma; neuroendocrine; differentiation
AB Gastrointestinal cancers have frequently shown neuroendocrine (NE) differentiation, but whether NE differentiation occurs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, tissue sections obtained from 43 patients with ESCC from a high-incidence area of Northern China were used for the assessing of NE differentiation by immunohistochemistry using antibody against chromogranin A (CGA). In addition, the malignant characteristics and proliferation capacity of CGA-positive cells were also examined by immunohistochemistry. The clinicopathological significance of these CGA-positive tumor cells in ESCC was assessed. Of 43 ESCC samples, CGAimmunoreactive tumor cells were detected in 10 cases (23.26%). However, the CGA-positive tumor cells were scattered at a very low number among non-immunoreactive tumor cells and were rarely constituted a major part of cancer cell nests. Only 4.65% (2/43) cases showed a high density (>10 cells but <1% of total tumor cell mass) of CGA-positive tumor cells. P53 immunoreactivity was frequently shown, while Ki67 was hard to detect in these CGApositive cells. In addition, no relationship between CGA positivity rate and clinicopathological parameters was found. Thus, we concluded that lowdensity CGA-positive tumor cells can be detected in ESCC, supporting the notion that heterogeneous NE differentiation also exists in tumors that lack neuroendocrine cells in their normal epithelial counterparts.
C1 [Yuan, Aping] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
[Liu, Jinzhong] the Fourth Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, Henan, China.
[Liu, Yiqing] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
[Cui, Guanglin] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
RP Cui, G (reprint author), the Second Affiliated Hospital of Zhengzhou University, Department of Medicine, Zhengzhou, China.
EM guanglin.cui@fagmed.uit.no
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Zhao M, Laissue JA, Zimmermann A: "Neuroendocrine" differentiation in hepatocellular carcinomas, HCCs): immunohistochemical reactivity is related to distinct tumor cell types, but not to tumor grade. Histol Histopathol 8:617-626, 1993
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 321
EP 325
PG 5
ER
PT J
AU Chang, JH
Yoo, ChB
Kim, WS
Lee, LB
Kim, HW
AF Chang, Jin Hee
Yoo, Chul Byong
Kim, Whe Sun
Lee, Lan Byung
Kim, Ho Woo
TI Significance of PML and p53 Protein as Molecular Prognostic Markers of Gallbladder Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gallbladder carcinoma; prognosis; PML protein; p53 protein
ID gallbladder carcinoma; prognosis; PML protein; p53 protein
AB Molecular markers for cancers are not only useful for cancer detection and prognostic prediction, but may also serve as potential therapeutic targets. In order to identify reliable molecular markers for prognostic prediction in gallbladder carcinoma (GBC), we evaluated the immunohistochemical expression of 15 proteins, namely p53, p27, p16, RB, Smad4, PTEN, FHIT, GSTP1, MGMT, E-cadherin, nm23, CD44, TIMP3, S100A4, and promyelocytic leukemia (PML) in 138 cases of GBC using the tissue microarray method. The prognostic significance was analyzed for each protein. Overexpression of p53 and S100A4, and loss of p27, p16, RB, Smad4, FHIT, E-cadherin and PML expression were associated with poor survival. In particular, PML and p53 showed considerable potential as independent prognostic markers. Patients with normal PML and p53 expression displayed favorable outcomes, compared to those showing abnormal expression of either or both proteins (49% vs. 23% in a 5-year survival rate; 60 months vs. 11 months in median survival, respectively; P=0.009). Thus, PML and p53 are potential candidates for development as clinically applicable molecular prognostic markers of GBC, and may be effective therapeutic targets for the disease in the future.
C1 [Chang, Jin Hee] National Cancer Center, Research Institute and HospitalSeoul, South Korea.
[Yoo, Chul Byong] National Cancer Center, Research Institute and HospitalSeoul, South Korea.
[Kim, Whe Sun] Seoul National University, Department of SurgerySeoul, South Korea.
[Lee, Lan Byung] Seoul National University, Department of AnatomySeoul, South Korea.
[Kim, Ho Woo] Seoul National University, Cancer Research Institute, 28 Yeongeon-dong, Jongno-gu, 110-799 Seoul, South Korea.
RP Kim, HW (reprint author), Seoul National University, Cancer Research Institute, 110-799 Seoul, South Korea.
EM woohokim@snu.ac.kr
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da Rocha AO, Coutinho LM, Scholl JG, Leboutte LD: The value of p53 protein expression in gallbladder carcinoma: analysis of 60 cases. Hepatogastroenterology 51:1310-1314, 2004
El-Deiry WS: The role of p53 in chemosensitivity and radiosensitivity. Oncogene 22:7486-7495, 2003
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Kawamoto T, Shoda J, Irimura T, Miyahara N, Furukawa M, Ueda T, Asano T, Kano M, Koike N, Fukao K, Tanaka N, Todoroki T: Expression of MUC1 mucins in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder. Clin Cancer Res 7:1333-1342, 2001
Kim YW, Huh SH, Park YK, Yoon TY, Lee SM, Hong SH: Expression of the c-erb-B2 and p53 protein in gallbladder carcinomas. Oncol Rep 8:1127-1132, 2001
Kohya N, Miyazaki K, Matsukura S, Yakushiji H, Kitajima Y, Kitahara K, Fukuhara M, Nakabeppu Y, Sekiguchi M: Deficient expression of O(6)-methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma. Ann Surg Oncol 9:371-379, 2002
Kwon SY, Chang HJ: Clinicopathological study of unsuspected carcinoma of gallbladder. J Korean Med Science 12: 519-522, 1997
Lee HS, Lee HK, Kim HS, Yang HK, Kim WH: Tumour suppressor gene expression correlates with gastric cancer prognosis. J Pathol 200:39-46, 2003
Levy AD, Murakata LA, Rohrmann CA: Gallbladder carcinoma: radiologic-pathologic correlation. Radiographics 21:295-314, 2001
Li X, Hui AM, Shi YZ, Takayama T, Makuuchi M: Reduced p21(WAF1/CIP1, expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder. Hum Pathol 32:771-777, 2001
Misra S, Chaturvedi A, Goel MM, Mehrotra R, Sharma ID, Srivastava AN, Misra NC: Overexpression of p53 protein in gallbladder carcinoma in North India. Eur J Surg Oncol 26:164- 167, 2000
Nakamura T, Ajiki T, Murao S, Kamigaki T, Maeda S, Ku Y, Kuroda Y: Prognostic significance of S100A4 expression in gallbladder cancer. Int J Oncol 20:937-941, 2002
Oshikiri T, Hida Y, Miyamoto M, Hashida H, Katoh K, Suzuoki M, Nakakubo Y, Hiraoka K, Shinohara T, Itoh T, Kondo S, Katoh H: RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer. Br J Cancer 85:1922-1927, 2001
Rego EM, Wang ZG, Peruzzi D, He LZ, Cordon-Cardo C, Pandolfi PP: Role of promyelocytic leukemia, PML, protein in tumor suppression. J Exp Med 193:521-529, 2001
Rosen DG, Huang X, Deavers MT, Malpica A, Silva EG, Liu J: Validation of tissue microarray technology in ovarian carcinoma. Mod Pathol 17:790-797, 2004
Shi YZ, Hui AM, Li X, Takayama T, Makuuchi M: Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16INK4 protein in gallbladder carcinomas. Clin Cancer Res 6:4096-4100, 2000
Soussi T, Caron de Fromentel C, May P: Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5:945- 952, 1990
Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, Suzuki M, Miyajima K, Zhou X, Bekele BN, Gazdar AF, Wistuba II: Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res 10:6126-6133, 2004
Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Kochli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi OP, Sauter G: Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 159:2249-2256, 2001
Varga M, Obrist P, Schneeberger S, Muhlmann G, Felgel- Farnholz C, Fong D, Zitt M, Brunhuber T, Schafer G, Gastl G, Spizzo G: Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res 10:3131-3136, 2004
Wistuba II, Sugio K, Hung J, Kishimoto Y, Virmani AK, Roa I, Albores-Saavedra J, Gazdar AF: Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile. Cancer Res 55:2511-2515, 1995
Wistuba II, Tang M, Maitra A, Alvarez H, Troncoso P, Pimentel F, Gazdar AF: Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma. Cancer Res 61:3795-3800, 2001
Wistuba II, Ashfaq R, Maitra A, Alvarez H, Riquelme E, Gazdar AF: Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma. Am J Pathol 160:2073-2079, 2002
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 326
EP 335
PG 10
ER
PT J
AU Croci, S
Landuzzi, L
Nicoletti, G
Palladini, A
Antognoli, A
De Giovanni, C
Nanni, P
Lollini, PL
AF Croci, Stefania
Landuzzi, Lorena
Nicoletti, Giordano
Palladini, Arianna
Antognoli, Agnese
De Giovanni, Carla
Nanni, Patrizia
Lollini, Pier-Luigi
TI Expression of Connective Tissue Growth Factor (CTGF/CCN2) in a Mouse Model of Rhabdomyosarcomagenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE rhabdomyosarcoma; mouse model; CCN proteins; CCN2/CTGF
ID rhabdomyosarcoma; mouse model; CCN proteins; CCN2/CTGF
AB Connective tissue growth factor (CTGF/CCN2) is a cysteine-rich matricellular protein that belongs to the CCN (CYR61, CTGF, NOV) protein family. It is highly expressed by human rhabdomyosarcoma cells and sustains their survival. In this study we investigated CCN2 expression in a mouse model of spontaneous rhabdomyosarcomagenesis that combines HER-2/neu oncogene activation and p53 oncosuppressor gene inactivation (BALB-p53neu mice). Murine rhabdomyosarcoma cells showed a 4-26 fold increase in CCN2 mRNA expression regarding to normal thigh muscle. Moreover, they expressed CCN2 protein at levels comparable to human rhabdomyosarcoma cells. Therefore BALBp53neu mice might be useful for the evaluation of the role played by CCN2 in rhabdomyosarcoma in vivo.
C1 [Croci, Stefania] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
[Landuzzi, Lorena] Istituti Ortopedici Rizzoli, Laboratorio di Ricerca OncologicaBologna, Italy.
[Nicoletti, Giordano] Istituti Ortopedici Rizzoli, Laboratorio di Ricerca OncologicaBologna, Italy.
[Palladini, Arianna] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
[Antognoli, Agnese] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
[De Giovanni, Carla] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
[Nanni, Patrizia] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
[Lollini, Pier-Luigi] University of Bologna, Department of Experimental Pathology, Cancer Research Section, Viale Filopanti 22, I-40126 Bologna, Italy.
RP Lollini, PL (reprint author), University of Bologna, Department of Experimental Pathology, Cancer Research Section, I-40126 Bologna, Italy.
EM pierluigi.lollini@unibo.it
CR Aikawa T, Gunn J, Spong SM et al: Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther 5: 1108-1116, 2006
Brigstock DR: The CCN family: a new stimulus package. J Endocrinol 178: 169-175, 2003
Croci S, Landuzzi L, Astolfi A et al: Inhibition of connective tissue growth factor, CTGF/CCN2, expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells. Cancer Res 64: 1730-1736, 2004
Dornhofer N, Spong S, Bennewith K et al: Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 66: 5816- 5827, 2006
Lin BR, Chang CC, Che TF et al: Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer. Gastroenterology 128: 9-23, 2005
Nanni P, Nicoletti G, De Giovanni C et al: Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice. Cancer Res 63: 2728-2732, 2003
Palladini A, Astolfi A, Croci S et al: Endothelin-3 production by human rhabdomyosarcoma: a possible new marker with a paracrine role. Eur J Cancer 42: 680-687, 2006
Perbal B: CCN proteins: multifunctional signalling regulators. Lancet 363: 62-64, 2004
Planque N, Perbal B: A structural approach to the role of CCN, CYR61/CTGF/NOV, proteins in tumourigenesis. Cancer Cell Int 3: 15, 2003
Shimo T, Kubota S, Yoshioka N et al: Pathogenic role of connective tissue growth factor, CTGF/CCN2, in osteolytic metastasis of breast cancer. J Bone Miner Res 21: 1045-1059, 2006
Yang DH, Kim HS, Wilson EM et al: Identification of glycosylated 38-kDa connective tissue growth factor, IGFBP-related protein 2, and proteolytic fragments in human biological fluids, and up-regulation of IGFBP-rP2 expression by TGF-beta in Hs578T human breast cancer cells. J Clin Endocrinol Metab 83: 2593-2596, 1998
Yang F, Tuxhorn JA, Ressler SJ et al: Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 65: 8887-8895, 2005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 336
EP 339
PG 4
ER
PT J
AU Remenar,
Szamel, I
Budai, B
Vincze, B
Gaudi, I
Gundy, S
Kasler, M
AF Remenar, Eva
Szamel, Iren
Budai, Barna
Vincze, Borbala
Gaudi, Istvan
Gundy, Sarolta
Kasler, Miklos
TI Increase of Hypophyseal Hormone Levels in Male Head and Neck Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck cancer; sex steroids; hypophysis hormones; alcoholic liver disease
ID head and neck cancer; sex steroids; hypophysis hormones; alcoholic liver disease
AB Head and neck squamous cell carcinoma (HNSCC) develops in at least 80% of cases in men with a history of smoking and heavy alcohol consumption, still it is only diagnosed in a small proportion of alcoholics. Endocrine milieu is an important factor in carcinogenesis and prognosis of several cancer types. The aim of our study was to investigate sex steroid and hypophyseal hormone status of male HNSCC patients in comparison to healthy volunteers and to patients with alcoholic liver disease, to determine possible hormonal alterations characteristic of cancer. Liver function (GGT level), and serum levels of gonadotropic hormones (FSH, LH, prolactin), sex steroids (estradiol, progesterone, testosterone) and sex hormone-binding globulin (SHBG) were compared in 130 male HNSCC patients, 54 patients with alcoholic liver disease but no known cancer, and 56 healthy controls. We found abnormal values of liver function in both HNSCC patients and alcoholics compared to healthy controls, suggesting the presence of alcoholic liver disease in the former group as well. On the other hand, a significant elevation in the level of DHEA, FSH and LH was observed in cancer patients exclusively. As a conclusion, abnormal alterations in sex steroid hormone levels can frequently be found in HNSCC patients, which may be caused in part by the alcoholic liver damage accompanying the disease. The significant increase in FSH and LH serum levels, observed only in the cancer patients, indicates that these hormones may play a role in the development and/or progression of HNSCC.
C1 [Remenar, Eva] National Institute of Oncology, Department of Head and Neck Surgery, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
[Szamel, Iren] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Budai, Barna] National Institute of Oncology, Central Clinical LaboratoryBudapest, Hungary.
[Vincze, Borbala] National Institute of Oncology, Department of BiochemistryBudapest, Hungary.
[Gaudi, Istvan] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Gundy, Sarolta] National Institute of Oncology, National Cancer RegistryBudapest, Hungary.
[Kasler, Miklos] National Institute of Oncology, Department of Head and Neck Surgery, Rath Gy. u. 7-9., H-1122 Budapest, Hungary.
RP Remenar, (reprint author), National Institute of Oncology, Department of Head and Neck Surgery, H-1122 Budapest, Hungary.
EM reva@oncol.hu
CR Tsugane S, Fahey MT, Sasaki S, Baba S: Alcohol consumption and all-cause and cancer mortality among middle-aged Japanese men: seven-year follow-up of the JPHC study cohort I. Japan Public Health Center. Am J Epidemiol 150: 1201-1207, 1999
Bray I, Brennan P, Boffetta P: Projections of alcohol- and tobacco-related cancer mortality in Central Europe. Int J Cancer 87: 122-128, 2000
Boffetta P, Ye W, Adami HO, Mucci LA, Nyren O: Risk of cancers of the lung, head and neck in patients hospitalized for alcoholism in Sweden. Br J Cancer 85: 678-682, 2001
World Health Organization: The tobacco atlas. Geneva; World Health Organization, 2002
Zeka A, Gore R, Kriebel D: Effects of alcohol and tobacco on aerodigestive cancer risks: a meta-regression analysis. Cancer Causes Control 14: 897-906, 2003
World Health Organization: Global status report on alcohol. Geneva; World Health Organization, 2004
Ezzati M, Henley SJ, Lopez AD, Thun MJ: Role of smoking in global and regional cancer epidemiology: Current patterns and data needs. Int J Cancer 116: 963-971, 2005
Boffetta P, Hashibe M: Alcohol and cancer. Lancet Oncol 7: 149-156, 2006
Bannister P, Losowsky MS: Sex hormones and chronic liver disease. J Hepatol 6: 258-262, 1988
Wang YJ, Wu JC, Lee SD, Tsai YT, Lo KJ: Gonadal dysfunction and changes in sex hormones in postnecrotic cirrhotic men: a matched study with alcoholic cirrhotic men. Hepatogastroenterology 38: 531-534, 1991
Martinez-Riera A, Santolaria-Fernandez F, Gonzalez Reimers E, Milena A, Gomez-Sirvent JL, Rodriguez-Moreno F, Gonzalez- Martin I, Rodriguez-Rodriguez E: Alcoholic hypogonadism: hormonal response to clomiphene. Alcohol 12: 581-587, 1995
Zietz B, Lock G, Plach B, Drobnik W, Grossmann J, Scholmerich J, Straub RH: Dysfunction of the hypothalamicpituitary- glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur J Gastroenterol Hepatol 15: 495-501, 2003
Patel JD, Bach PB, Kris MG: Lung cancer in US women. A contemporary epidemic. JAMA 291: 1763-1768, 2004
Yoo HJ, Sepkovic DW, Bradlow HL, Yu GP, Sirilian HV, Schantz SP: Estrogen metabolism as a risk factor for head and neck cancer. Otolaryngol Head Neck Surg 124: 241-247, 2001
Kawai H, Ishii A, Washiya K, Konno T, Kon H, Yamaya C, Ono I, Minamiya Y, Ogawa J: Estrogen receptor a and b are prognostic factors in non-small cell lung cancer. Clin Cancer Res 11: 5084-5089, 2005
Chan JA, Meyerhardt JA, Chan AT, Giovanucci EL, Colditz GA, Fuchs CS: Hormone replacement therapy and survival after colorectal cancer diagnosis. J Clin Oncol 24: 5680-5686, 2006
Giannitrapani L, Soresi M, La Spada E, Cervello M, D’Alessandro N, Montalto G: Sex hormones and risk of liver tumor. Ann N Y Acad Sci 1089: 228-236, 2006
Poynard T, Aubert A, Bedossa P, Abella A, Naveau S, Paraf F, Chaput JC: A simple biological index for detection of alcoholic liver disease in drinkers. Gastroenterology 100: 1397-1402, 1991
Yokoyama A, Muramatsu T, Ohmori T, Yokoyama T, Okuyama K, Takahashi H, Hasegawa Y, Higuchi S, Maruyama K, Shirakura K, Ishii H: Alcohol-related cancers and aldehyde dehydrogenase- 2 in Japanese alcoholics. Carcinogenesis 19: 1383-1387, 1998
Makimoto K, Higuchi S: Alcohol consumption as a major risk factor for the rise in liver cancer mortality rates in Japanese men. Int J Epidemiol 28: 30-34, 1999
Duvoux C, Delacroix I, Richardet J-P, Roudot-Thoraval F, Metreau JM, Faqniez PL, Dhumeaux D, Cherqui D: Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis. Transplantation 67: 418-421, 1999
Kopp MS, Rethelyi JC: Where psychology meets physiology: chronic stress and premature mortality - the Central-Eastern European health paradox. Brain Res Bull 62: 351-367, 2004
Lukits J, Remenar E, Raso E, Ladanyi A, Kasler M, Timar J: Molecular identification, expression and prognostic role of estrogen- and progesterone receptors in head and neck cancer. Int J Oncol 30:155-160, 2007
Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS: The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastases. BJU Int 89: 710-713, 2002
Bhatavdekar JM, Patel DD, Vora HH, Balar DB: Circulating markers and growth factors as prognosticators in men with advanced tongue cancer. Tumour Biol 14: 55-58, 1993
Bhatavdekar JM, Patel DD, Chikhlikar PR, Mehta RH, Vora HH, Karelia NH, Ghosh N, Shah NG, Suthar TP, Neema JP, et al: Levels of circulating peptide and steroid hormones in men with lung cancer. Neoplasma 41: 101-103, 1994
Bhatavdekar JM, Patel DD, Vora HH, Shah NG, Chikhlikar PR, Ghosh N: Prolactin as a local growth promoter in patients with locally advanced tongue cancer: GCRI experience. Head Neck 22: 257-264, 2000
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 341
EP 344
PG 4
ER
PT J
AU Kojima, M
Nakamura, N
Shimizu, K
Nishikawa, M
Matsumoto, M
Higuchi, K
Yamane, N
Tsukamoto, N
Tamaki, Y
Inagaki, H
AF Kojima, Masaru
Nakamura, Naoya
Shimizu, Kazuhiko
Nishikawa, Masahumi
Matsumoto, Morio
Higuchi, Keiko
Yamane, Nobuo
Tsukamoto, Norihumi
Tamaki, Yoshio
Inagaki, Hiroshi
TI Histopathological Variation of Primary Mucosa-associated Lymphoid Tissue Lymphoma of the Oral Cavity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mucosa-associated lymphoid tissue lymphoma; oral cavity; follicular colonization; immunohistochemistry
ID mucosa-associated lymphoid tissue lymphoma; oral cavity; follicular colonization; immunohistochemistry
AB Primary mucosa-associated lymphoid tissue (MALT) type lymphoma arising in the oral cavity is rare. We examined histopathologic, immunohistological and genotypic findings of seven cases of intraoral MALT lymphoma using formalin-fixed paraffin-embedded tissues. Histologically, two variants have been delineated. (i) In four cases of minor salivary gland type, the lymphoid follicles were surrounded by centrocyte-like (CCL) cells with occasional follicular colonization. The CCL cells invaded the residual salivary gland duct resulting in a lymphoepithelial lesion. CCL cells frequently showed plasmacytic differentiation. (ii) In three cases of follicular growth type, the lesion was characterized by follicular growth pattern resulting from prominent follicular colonization. CCL cells showed minimal plasma cell differentiation. There was no residual epithelial component detected even by cytokeratin immunostaining. There were no Epstein-Barr virus-encoded small RNA-positive cells detected by in situ hybridization. API2-MALT1 fusion transcript does not appear to be associated with either histological variant of primary intraoral MALT lymphoma.
C1 [Kojima, Masaru] Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 617-1, Takabayashinishi-cho, 373-8550 Ohta, Japan.
[Nakamura, Naoya] Tokai University School of Medicine, Department of PathologyIsehara, Japan.
[Shimizu, Kazuhiko] Ashikaga Red Cross Hospital, Department of Pathology and Clinical LaboratoriesAshikaga, Japan.
[Nishikawa, Masahumi] National Tochigi Hospital, Department of Pathology and Clinical LaboratoriesUtsunomiya, Japan.
[Matsumoto, Morio] National Nishigunma Hospital, Department of HematologyShibukawa, Japan.
[Higuchi, Keiko] Gunma Cancer Center Hospital, Department of RadiologyOhta, Japan.
[Yamane, Nobuo] Ashikaga Red Cross Hospital, Department of Oral SurgeryAshikaga, Japan.
[Tsukamoto, Norihumi] Gunma University, Department of Medicine and Clinical ScienceGunma, Japan.
[Tamaki, Yoshio] Gunma Cancer Center Hospital, Department of RadiologyOhta, Japan.
[Inagaki, Hiroshi] Nagoya City University Graduate School of Medical Science, Department of PathologyNagoya, Japan.
RP Kojima, M (reprint author), Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 373-8550 Ohta, Japan.
EM mkojima@gunma-cc.jp
CR Epstein JB, Epstein JD, Le ND, Gorsky M: Characterization of oral and paraoral malignant lymphoma: a population-based review of 361 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:519-525, 2001
Takahashi H, Fujita S, Okabe H, Tsuda N, Tezuka F: Immunophenotypic analysis of extranodal non-Hodgkin’s lymphomas in oral cavity. Pathol Res Pract 189:300-311, 1993
Solomides CC, Miller AS, Christman RA, Talwar J, Simpkins H. Lymphomas of the oral cavity: Histology, immunologic type, and incidence of Epstein-Barr virus infection. Hum Pathol 33:153-157, 2002
Odell EW, Lombardi T, Shirlaw PJ, White CAM: Minor salivary gland hyalinization and amyloidosis in low-grade lymphoma of MALT. J Oral Pathol Med 27:229-232, 1998
Sakabe H, Bamba M, Nomura K, Kitamura S, Segawa H, Yasui H, Inoue T, Taniwaki M, Fujiyama Y, Bamba T: MALT lymphoma at the base of the tongue developing without any background of immunodeficiency or autoimmune disease. Leuk Lymphoma 44:875-878, 2003
Honda K, Kusama H, Takagi S, Sekine S, Noguchi M, Chiba H: Diagnosis of intra-oral MALT lymphoma using seminested polymerase chain reaction. Br J Oral Maxillofac Surg 42:28- 32, 2004
Sakuma H, Okabe M, Yokoi M, Eimoto T, Inagaki H: Spontaneous regression of intraoral mucosa-associated lymphoid tissue lymphoma: molecular study of a case. Pathol Intern 56:331-335, 2006
Kojima M, Sugihara S, Iijima M, Ono T, Yoshizumi T, Masawa N: Marginal zone B-cell lymphoma of minor salivary gland representing tumor-forming amyloidosis of the oral cavity. A case report. J Oral Pathol Med 35:314-316, 2006
Inagaki H, Chan JKC, Ng JWM, Okabe M, Yoshino T, Okamoto M, Ogawa H, Matsushita H, Yokose T, Matsuno Y, Nakamura N, Nagasaka T, Ueda R, Eimoto T, Nakamura S: Primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type exhibits distinctive clinicopathological and molecular features. Am J Pathol 160:1435-1443, 2002
Isaacson PG, Norton AJ: Extranodal lymphomas. Churchill Livingstone, Edinburgh, 1994
Chan ALC, Chan JKC. Haematolymphoid tumors. In: Pathology and genetics of tumours of head and neck., Eds: Barnes L, Evenson JW, Reichart P, Sidransky D), IARCPress, Lyon, 2005, pp 199-205
Isaacson PG, Wotherspoon AC, Diss T, Pan L: Follicular colonization of B-cell lymphoma of mucosa-associated lymphoid tissue. Am J Surg Pathol 15:819-828, 1991
Kojima M, Yamanaka S, Yoshida T, Shimizu K, Murayama K, Ohno Y, Itoh H, Motoori T, Masawa N, Nakamura S: Histological variety of floral variant of follicular lymphoma. A report of 13 Japanese cases. APMIS 114:626-632, 2006
Lai R, Weiss LM, Chang KL, Arber DA: Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphoma. Am J Clin Pathol 111:488-494, 1999
Wang T, Lasota J, Hanau CA, Miettinen M: Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphoma but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferation is of diagnostic value. APMIS 103: 655-662, 1995
Isaacson PG, Du M-Q: Gastrointestinal lymphoma: where morphology meets molecular biology. J Pathol 205:255-274, 2005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 345
EP 349
PG 5
ER
PT J
AU Magyar, Z
Berkes, E
Csapo, Zs
Papp, Z
AF Magyar, Zoltan
Berkes, Eniko
Csapo, Zsolt
Papp, Zoltan
TI Effect of Hormone Replacement Therapy on Postmenopausal Endometrial Bleeding
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE climacterium; postmenopausal hormone therapy; menopause; irregular bleeding
ID climacterium; postmenopausal hormone therapy; menopause; irregular bleeding
AB The aim of the study was to determine the effect of postmenopausal hormone replacement therapy (HRT) (treatment using estrogen only and sequential and continuous combined estrogen-progestogen treatment) on endometrial bleeding and histological changes of the endometrium. In a six-year period (2000-2005), 5893 patients were given care and the incidence of postmenopausal uterine bleeding was detected in groups of patients having and not having received hormonal treatment at the Menopause Outpatient Unit of the authors’ department. In the case of bleeding, fractioned abrasion was performed and the samples were analyzed histologically. Among the postmenopausal patients who had not been given hormonal treatment, the incidence of bleeding episodes was significantly higher as among those having received hormonal treatment. In the samples, findings of proliferative endometrium occurred significantly more often in case of non-treated patients and those treated with sequential combined hormone therapy compared to patients receiving continuous combined hormone therapy. Although it was statistically not significant, hyperplasia simplex and complex together showed a tendency of reduced incidence in patients medicated by continuous combined treatment. These findings suggest that continuous combined hormonal treatment started at the right time (even before the menopause) may reduce the chances of the development of hyperplasia. A significantly higher incidence of hyperplasia was noted in patients using estrogen treatment only. It is possible that unopposed estrogen treatment further engraves an already diagnosed endometrial hyperplasia. In the group having received hormonal treatment, no complex hyperplasia accompanied by atypia occurred, only hyperplasia simplex was diagnosed in these cases. As a result of continuous reliance on combined preparations, the endometrium had become atrophied, therefore the chance of hyperplasia-related changes and of bleeding as a side effect decreased significantly. According to the authors’ experience, hormonal treatment does not pose a risk to the development of endometrial carcinoma; on the contrary, continuous combined preparations appear to reduce the risk of hyperplasia and, indirectly, the chances of the development of adenocarcinoma.
C1 [Magyar, Zoltan] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross u. 27, H-1088 Budapest, Hungary.
[Berkes, Eniko] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross u. 27, H-1088 Budapest, Hungary.
[Csapo, Zsolt] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross u. 27, H-1088 Budapest, Hungary.
[Papp, Zoltan] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross u. 27, H-1088 Budapest, Hungary.
RP Magyar, Z (reprint author), Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, H-1088 Budapest, Hungary.
EM magyar@noi1.sote.hu
CR Anastasiadis PG, Koutlaki NG, Skaphida PG et al: Endometrial polypus: prevalence, detection, and malignant potential in women with abnormal uterine bleeding. Eur J Gynaecol Oncol 21: 180-183, 2000.
Astrup K, Olivarius N: Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 83: 203-205, 2004.
Bachmann LM, Riet G, Clark TJ et al: Probability analysis for diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding: an approach for a rational diagnostic workup. Acta Obstet Gynecol Scand 82: 1-6, 2003.
Bernard JP, Rizk E, Camatte S et al: Saline contrast sonohysterography in the preoperative assessment of benign intrauterine disorders. Ultrasound Obstet Gynecol 17: 145-149, 2001.
Burger HG, Dudley EC, Hopper JL et al: The endocrinology of the menopausal transition: a cross-sectional study of a population- based sample. J Clin Endocrinol Metab 80: 3537-3545, 1995.
Cerin A, Heldaas K, Moeller B: Adverse endometrial effects of long-cycle estrogen and progestagen replacement therapy. The Scandinavian Long-Cycle Study Group. New Engl J Med 334: 668-669, 1996.
Clark TJ, Barton PM, Coomarasamy A et al: Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies. Br J Obstet Gynecol 113: 502-510, 2006.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 351
EP 359
PG 9
ER
PT J
AU Dehaghani, SA
Ghiam, FA
Hosseini, M
Mansouri, S
Ghaderi, A
AF Dehaghani, Samsami Alamtaj
Ghiam, Fotouhi Alireza
Hosseini, Marjan
Mansouri, Sareh
Ghaderi, Abbas
TI Factors Influencing Serum Concentration of CA125 and CA15-3 in Iranian Healthy Postmenopausal Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast health; menopause; cancer
ID breast health; menopause; cancer
AB Screening for breast and ovarian cancers are required due to the late stage at diagnosis and poor survival. Serum CA125 and CA15-3 are important cancerdetecting agents in patients with ovarian and breast cancers, respectively. Elevation of CA125 and CA15-3 level correlates with malignant and non-malignant conditions. Moreover, a series of individual characteristics affect the serum level of these markers. The objective of the present study was to evaluate CA125 and CA15-3 levels in cancer-free postmenopausal women to investigate the impacts of patient parameters on the serum level of these markers. 203 subjects were studied prospectively. Serum CA125 and CA15-3 assessment was done subsequent to the direct interview. The associations between marker levels and presenting features were examined. CA125 and CA15-3 levels were elevated in 35 (17.2%) and 12 (5.9%) of persons, respectively. A higher CA125 level was associated with advanced age (p = 0.046), while a lower level was correlated with hormone replacement therapy (HRT) and having smoking habits (p = 0.000 and p = 0.01, respectively). CA15-3 level was remarkably lower amongst oral contraceptive (OCP) users (p = 0.03). Serum marker levels were not significantly related to menarche age, age at menopause, height, weight, BMI and parity. Serum CA125 is imperative indicator for malignancies of the ovary; however, personal and medical factors influence its serum level. A fair interpretation of results must be due to an accurate attention to the individual characteristics.
C1 [Dehaghani, Samsami Alamtaj] Shiraz University of Medical Sciences, Department of Obstetrics and GynecologyShiraz, Iran.
[Ghiam, Fotouhi Alireza] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Hosseini, Marjan] Shiraz University of Medical Sciences, Department of Obstetrics and GynecologyShiraz, Iran.
[Mansouri, Sareh] Shiraz University of Medical Sciences, Department of Obstetrics and GynecologyShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Ghaderi, A (reprint author), Shiraz University of Medical Sciences, Institute for Cancer Research, Shiraz, Iran.
EM ghaderia@sums.ac.ir
CR Taechakraichana N, Jaisamrarn U, Panyakhamlerd K, Chaikittisilpa S, Limpaphayom KK: Climacteric: concept, consequence and care. J Med Assoc Thai 85:S1-15, 2002.
Rymer J, Morris EP: Extracts from “Clinical evidence”: Menopausal symptoms. BMJ 321: 1516-1519, 2000.
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Jamjan L, Jerayingmongkol P: Self-image of people in their fifties. Nurs Health Sci 4:A4, 2002.
Pike MC, Pearce CL, Wu AH: Prevention of cancers of the breast, endometrium and ovary. Oncogene 23: 6379-6391, 2004.
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Johnson KC, Hu J, Mao Y: Passive and active smoking and breast cancer risk in Canada. Cancer Causes Control 11: 211- 221, 2000.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 360
EP 364
PG 5
ER
PT J
AU Xin, B
Yokoyama, Y
Shigeto, T
Mizunuma, H
AF Xin, Bing
Yokoyama, Yoshihito
Shigeto, Tatsuhiko
Mizunuma, Hideki
TI Anti-Tumor Effect of Non-Steroidal Anti-Inflammatory Drugs on Human Ovarian Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE non-steroidal anti-inflammatory drugs; selective COX-2 inhibitor; non-specific COX inhibitor; meloxicam; ovarian cancer
ID non-steroidal anti-inflammatory drugs; selective COX-2 inhibitor; non-specific COX inhibitor; meloxicam; ovarian cancer
AB Many reports have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) suppress malignant transformation and tumor growth, and some NSAIDs are expected to be new anti-cancer agents. In this study, we examined the anti-tumor effects of the non-specific cyclooxygenase (COX) inhibitors aspirin and piroxicam, and the selective COX-2 inhibitor meloxicam on xenotransplanted ovarian cancer. Tumor growth and survival were compared in female nu/nu mice, xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors and treated with aspirin (200 ppm in diet, everyday), piroxicam (150 ppm in diet, everyday) or meloxicam (162 ppm in diet, everyday). Al, of the agents tested significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously as compared to the control. There was a significant difference in inhibition of OVCAR-3 tumor growth between meloxicam and aspirin treatment. Meloxicam and piroxicam treatment significantly prolonged survival of mice with malignant ascites derived from DISS cells as compared to control and aspirin treatment. Mice treated with meloxicam survived significantly longer than those treated with piroxicam. There was no significant difference in survival between control and aspirin treatment. Necropsy revealed that one of the 6 cancer-bearing mice treated with piroxicam suffered from stomach perforation. These results indicate that a selective COX-2 inhibitor produces greater anti-tumor effect against ovarian cancer than a nonselective COX inhibitor and that meloxicam may have a potential of leading to a novel therapeutic strategy against ovarian cancer.
C1 [Xin, Bing] Hirosaki University School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, 036-8562 Hirosaki, Japan.
[Yokoyama, Yoshihito] Hirosaki University School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, 036-8562 Hirosaki, Japan.
[Shigeto, Tatsuhiko] Hirosaki University School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, 036-8562 Hirosaki, Japan.
[Mizunuma, Hideki] Hirosaki University School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, 036-8562 Hirosaki, Japan.
RP Yokoyama, Y (reprint author), Hirosaki University School of Medicine, Department of Obstetrics and Gynecology, 036-8562 Hirosaki, Japan.
EM yokoyama@cc.hirosaki-u.ac.jp
CR Aas AT, Tonnessen TI, Brun A, Salford LG: Growth inhibition of rat glioma cells in vitro and in vivo by aspirin. J Neurooncol 24: 171-180, 1995.
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Baron JA, Sandlers RS: Non-steroidal anti-inflammatory drugs and cancer prevention. Annu Rev Med 51: 511-523, 2000.
Blanco FJ, Guitian R, Moreno J, et al: Effect of anti-inflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol 26: 1366-1373, 1999.
Cramer DW, Harlow BL, Titus-Ernstoff L, et al: Over-thecounter analgesics and risk of ovarian cancer. Lancet 351: 104- 107, 1998.
Craven PA, DeRubertis FR: Effect of aspirin on 1,2-dimethylhydrazine- induced colonic carcinogenesis. Carcinogenesis 13: 541-546, 1992.
Denkert C, Kobel M, Pest S, et al: Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma. Am J Pathol 160: 893-903, 2002.
di Palma A, Matarese G, Leone V, et al: Aspirin reduces the outcome of anticancer therapy in Meth A-bearing mice through activation of AKT-glycogen synthase kinase signaling. Mol Cancer Ther 5: 1318-1324, 2006.
Din FV, Dunlop MG, Stark LA: Evidence for colorectal cancer cell specificity of aspirin effects on NFB signalling and apoptosis. Br J Cancer 91: 381-388, 2004.
Drake JG, Becker JL: Aspirin-induced inhibition of ovarian tumor cell growth. J Obstet Gynecol 100: 677-682, 2002.
Duperron C, Castonguay A: Chemoprevention efficacies of aspirin and sulindac against lung tumorigenesis in A/J mice. Carcinogenesis 18: 1001-1006, 1997.
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Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics. Ca Cancer J Clin 50: 7-33, 2000.
Goldman AP, Williams CS, Sheng H, et al: Meloxicam inhibits the growth of colorectal cancer cells. Carcinogenesis 19: 2195- 2199, 1998.
Henry D, Lim LLY, Rodriguez LS, et al: Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. Br Med J 312: 1563-1566, 1996.
Kern MA, Schoneweis MM, Sahli D, et al: Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implant in nude mice. Carcinogenesis 25: 1193-1199, 2004.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 365
EP 369
PG 5
ER
PT J
AU Pecina-Slaus, N
Niku Eva-Martic, T
Beros, V
Davor, T
AF Pecina-Slaus, Nives
Niku Eva-Martic, Tamara
Beros, Vili
Davor, Tomas
TI Genetic Alterations of E-cadherin and Beta-Catenin in Germinoma and Teratoma: Report of Two Central Nervous System Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE germinoma; teratoma; E-cadherin gene (CDH1); beta-catenin gene (CTNNB1); Wnt signaling pathway
ID germinoma; teratoma; E-cadherin gene (CDH1); beta-catenin gene (CTNNB1); Wnt signaling pathway
AB The genetic basis as well as mechanisms of development of germ cell tumors of the CNS are still unexplained. In the present article changes of Ecadherin (CDH1) and beta-catenin (CTNNB1) genes in two CNS germ cell tumors are reported. Both gene products are components of adherens junctions, but are also involved in the Wnt signaling pathway. A case of germinoma of the central nervous system and a case of spinal channel teratoma were tested for loss of heterozygosity (LOH) of E-cadherin gene by PCR amplification of tetranucleotide polymorphism (D16S752). Changes of beta-catenin were tested by heteroduplex method. Both germ cell tumors analyzed demonstrated LOH of the CDH1 gene. Analysis of exon 3 of the CTNNB1 gene showed additional band in the germinoma, suggesting that this sample harbors mutation in the beta-catenin gene. Immunostaining showed that LOHs in our samples were accompanied with the absence of E-cadherin protein. We also investigated E-cadherin expression in four other germinomas, of which three were negative and one was mildly positive. Our findings may contribute to better understanding of the genetic profile of germ cell tumors.
C1 [Pecina-Slaus, Nives] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, alata 3,, HR-10000 Zagreb, Croatia.
[Niku Eva-Martic, Tamara] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, alata 3,, HR-10000 Zagreb, Croatia.
[Beros, Vili] University Hospital Sisters of Charity, Department of NeurosurgeryZagreb, Croatia.
[Davor, Tomas] University Hospital Sisters of Charity, Ljudevit Jurak Department of PathologyZagreb, Croatia.
RP Pecina-Slaus, N (reprint author), School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, HR-10000 Zagreb, Croatia.
EM nina@mef.hr
CR Adamah DJ, Gokhale PJ, Eastwood DJ, Goepel J, Walsh JR, Moore HD, Andrews PW: Dysfunction of the mitotic:meiotic switch as a potential cause of neoplastic conversion of primordial germ cells. Int J Androl 29:219-227, 2006
Biegel JA: Cytogenetics and molecular genetics of childhood brain tumors. Neuro-oncol 1:139-151, 1999
Bussey KJ, Lawce HJ, Olson SB, Arthur DC, Kalousek DK, Krailo M, Giller R, Heifetz S, Womer R, Magenis RE: Chromosome abnormalities of eighty-one pediatric germ cell tumors: sex-, age-, site-, and histopathology-related differences – a Children’s Cancer Group study. Genes Chromosomes Cancer 25:134-146, 1999
Ellison DW, Onilude OE, Lindsey JC, Lusher ME, Weston CL, Taylor RE, Pearson AD, Clifford SC: Beta-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumour Committee. J Clin Oncol 23:7951-7957, 2005
Fritsch MK, Schneider DT, Schuster AE, Murdoch FE, Perlman EJ: Activation of Wnt/beta-catenin signaling in distinct histologic subtypes of human germ cell tumors. Pediatr Dev Pathol 9:115-131, 2006
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW: Identification of c-MYC as a target of the APC pathway. Science 281:1509-1512, 1998
Hejazi N, Witzmann A: Spinal intramedullary teratoma with exophytic components: report of two cases and review of the literature. Neurosurg Rev 26:113-116, 2003
Honecker F, Kersemaekers AM, Molier M, Van Weeren PC, Stoop H, De Krijger RR, Wolffenbuttel KP, Oosterhuis W, Bokemeyer C, Looijenga LH: Involvement of E-cadherin and betacatenin in germ cell tumours and in normal male fetal germ cell development. J Pathol 204:167-174, 2004
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Yokota N, Nishizawa S, Ohta S, Date H, Sugimura H, Namba H, Maekawa M: Role of wnt pathway in medulloblastoma oncogenesis. Int J Cancer 101:198-201, 2002
Yu X, Malenka RC: Beta-catenin is critical for dendritic morphogenesis. Nature Neurosci 6:1169-1177, 2003
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 370
EP 374
PG 5
ER
PT J
AU Solis-Coria, A
Vargas-Gonzalez, R
Sotelo-Avila, C
AF Solis-Coria, Araceli
Vargas-Gonzalez, Roberto
Sotelo-Avila, Cirilo
TI Rhabdomyomatous Mesenchymal Hamartoma Presenting as a Skin Tag in the Sternoclavicular Area
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE rhabdomyomatous mesenchymal hamartoma; striated muscle hamartoma
ID rhabdomyomatous mesenchymal hamartoma; striated muscle hamartoma
AB Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital lesion of the dermis and subdermis. It has been described predominantly in newborns, with 30 cases reported in the English literature. Typically, it appears as a skin tag, papule, nodule or a mass involving the face or sternal notch. A 28-day-old girl presented with a 1.4 x 0.8 cm soft skin tag in the right sternoclavicular area. Physical examination revealed no congenital anomalies. A shaved biopsy showed that the core of the lesion contained striated muscle fibers mixed with hair follicles and sebaceous and eccrine glands. Thin epidermis lined the outside of the tag. We report a patient with a RMH in a site not previously reported and discuss the differential diagnosis.
C1 [Solis-Coria, Araceli] Clinica de Dermatologia y Cirugia Estetica de PueblaPuebla, Mexico.
[Vargas-Gonzalez, Roberto] Hospital Para el Nino Poblano, Laboratorio de Inmunopatologia de Puebla and Department of Pathology, Km 1.5 Carretera Federal Puebla, 72190 Atlixco, Puebla, Mexico.
[Sotelo-Avila, Cirilo] Cardinal Glennon Children’s Medical Center, Department of PathologySt. Louis, MO, USA.
RP Vargas-Gonzalez, R (reprint author), Hospital Para el Nino Poblano, Laboratorio de Inmunopatologia de Puebla and Department of Pathology, 72190 Atlixco, Puebla, Mexico.
EM soncoy@msn.com
CR Hendrick SJ, Sanchez RL, Blackwell SJ, Raimer SS: Striated muscle hamartoma: Description of two cases. Pediatr Dermatol 3:153-157, 1986
Read RW, Burnstine M, Rowland JM, Zamir E, Rao NA: Rhabdomyomatous mesenchymal hamartoma of the eyelid. Report of a case and literature review. Ophthalmol 108:798-803, 2001
Rosenberg AS, Kirk J, Morgan MB: Rhabdomyomatous mesenchymal hamartoma: an unusual dermal entity with a report of two cases and review of the literature. J Cutan Pathol 29: 238- 243, 2002
Mills AE: Rhabdomyomatous mesenchymal hamartoma of skin. Am J Dermatopathol 11:58-63, 1989
Elgart GW, Patterson JW: Congenital midline hamartoma: case report with histochemical and immunohistochemical findings. Pediatr Dermatol 7:199-201, 1990
Shan EE, Garen PD, Pai GS, Levkoff AH, Hagerty RC, Maize JC: Multiple rhabdomyomatous mesenchymal hamartomas of skin. Am J Dermatopathol 12:485-491, 1990
Sanchez RL, Raimer SS: Clinical and histologic features of striated muscle hamartoma: possible relationship to Delleman´s syndrome, case report). J Cutan Pathol 21:40-46, 1994
Jansen T, Romiti R, Altmeyer P: Accessory tragus: Report of two cases and review of the literature. Pediatr Dermatol 17:391-394, 2000
Bergevin MA, Sheft Stan, Myer III C, Mc Adams A: Congenital midline cervical cleft. Pediatr Pathol 9: 731-739, 1989
Whitaker SR, Sprinkle M, Chov SM: Nasal glioma. Arch Otolaryngol 107:550-554, 1981.
Sotelo AC, Bale PM: Subdermal fibrous hamartoma of infancy: pathology of 40 cases and differential diagnosis. Pediatr Pathol 14:39-52, 1994
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Murphy GF: Dermatopathology.1st ed, W.B. Saunders Company, 1995, pp 191-192
Scrivener Y, Petiau P, Rodier-Bruant C, Cribier B, Heid E, Grosshans E: Perianal striated muscle hamartoma associated with hemangioma. Pediatr Dermatol 15:274-276, 1998
Nakanishi H, Hashimoto I, Takiwaki H, Urano Y, Arase S: Striated muscle hamartoma of the nostril. J Dermatol 22:504-507, 1995
Hayes M, van der Westhuizen N: Congenital rhabdomyomatous mesenchymal hamartoma, letter). Am J Dermatopathol 14:64- 65, 1992
Katsumata M, Keong CH, Satoh T: Rhabdomyomatous mesenchymal hamartoma of skin. J Dermatol 17:384-387, 1990
Grilli R, Escalonilla P, Soriano ML, Farina C, Renedo G, Martin L, Requena L: The so-called striated muscle hamartoma is a hamartoma of cutaneous adnexa and mesenchyme, but not of striated muscle, letter). Acta Dermatol Venereol 78: 390, 1998
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Chen SH, Driscoll MS, Sanchez RL, Raimer SS: A flesh-colored papule on the neck of a child. Pediatr Dermatol 16:65-67, 1999
Ashfaq R, Timmons CF: Rhabdomyomatous mesenchymal hamartoma of skin. Pediatr Pathol 12:731-735, 1992
Farris PE, Manning S, Vuitch F: Rhabdomyomatous mesenchymal hamartoma. Am J Dermatopathol 16:73-75, 1994
Chang CP, Chen GS: Rhabdomyomatous mesenchymal hamartoma: a plaque-type variant in an adult. Kaohsiung J Med Sci 21:185-188, 2005
Takeyama J, Hayashi T, Sanada T, Shimanuki Y, Saito M, Shirane R: Rhabdomyomatous mesenchymal hamartoma associated with nasofrontal meningocele and dermoid cyst. J Cutan Pathol 32:310-313, 2005
Ortak T, Orbay H, Unlu E, Uysal C, Uraloglu M, Sensoz OM: Rhabdomyomatous mesenchymal hamartoma. J Craniofac Surg 16:1135-1137, 2005
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 375
EP 378
PG 4
ER
PT J
AU Cantu De Leon, D
Perez Montiel, D
Chanona Vilchis, J
AF Cantu De Leon, David
Perez Montiel, Delia
Chanona Vilchis, Jose
TI Unusual Case of Subcutaneous Angiosarcoma Metastatic to the Ovary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE ovary; metastatic sarcoma; angiosarcoma
ID ovary; metastatic sarcoma; angiosarcoma
AB The ovaries are common sites for metastatic disease, however, the most frequent ones are carcinomas. Metastatic sarcomas are very rare in ovary and most of them arise from genital tract. We present the case of a 33-year-old woman with subcutaneous angiosarcoma who had metastatic disease to the ovary resulting in acute abdominal pain. Discussion of the case and a review of the literature are presented.
C1 [Cantu De Leon, David] Instituto Nacional de Cancerologia, Department of Surgical Oncology, Av San Fernando #22 Col Seccion XVI, 14080 Mexico City, Mexico.
[Perez Montiel, Delia] Instituto Nacional de Cancerologia, Department of PathologyMexico City, Mexico.
[Chanona Vilchis, Jose] Instituto Nacional de Cancerologia, Department of PathologyMexico City, Mexico.
RP Cantu De Leon, D (reprint author), Instituto Nacional de Cancerologia, Department of Surgical Oncology, 14080 Mexico City, Mexico.
EM dcantu@itesm.mx
CR Moore RG, Chung M, Granai CO, et al: Incidence of metastasis to the ovaries from nongenital tract primary tumors. Gynecol Oncol 93:87-89, 2004.
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Young RH, Scully RE: Sarcomas metastatic to the ovary: A report of 21 cases. Int J Gynecol Pathol 9:931-952, 1990.
Mazur MT, Hsueh S, Gersell DJ: Metastases to the female genital tract. Analysis of 325 cases. Cancer 53:1978-1984, 1984.
Fujiwara K, Ohishi Y, Koike H, et al: Clinical implications of metastases to the ovary. Gynecol Oncol 59:124-128, 1995.
Blamey S, McDermott F, Pihl E, et al: Ovarian involvement in adenocarcinoma of the colon and rectum. Surg Gynecol Obstet 153:42-44, 1981.
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Platt JS, Rogers SJ, Flynn CA, et al. Primary angiosarcoma of the ovary: A case report and review of the literature. Gynecol Oncol 73: 443-446, 1999.
Scully R. Young RH, Clement PB: Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament. Armed Forces Institute of Pathology, 3rd series, 1998.
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Yada-Hashimoto N, Yamamoto T, Kamiura S, et al: Metastatic ovarian tumors: A review of 64 cases. Gynecol Oncol 89:314- 317, 2003.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 379
EP 381
PG 3
ER
PT J
AU Szynglarewicz, B
Matkowski, R
Smorag, Z
Forgacz, J
Pudelko, M
Kornafel, J
AF Szynglarewicz, Bartlomiej
Matkowski, Rafal
Smorag, Zbigniew
Forgacz, Jozef
Pudelko, Marek
Kornafel, Jan
TI Hepatitis C Virus Infection and Locally Advanced Splenic Marginal Zone Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE hepatitis C; splenic neoplasm; marginal zone lymphoma
ID hepatitis C; splenic neoplasm; marginal zone lymphoma
AB Splenic marginal zone lymphoma (SMZL) is a rare malignant B-cell neoplasm, usually with an indolent clinical course and favorable prognosis. Treatment options include chemotherapy, surgery, radiation and immunotherapy. In some recent studies an increased incidence of hepatitis C virus (HCV) infection in patients with SMZL was reported and its possible role in lymphomagenesis was emphasized. A 66-year-old woman with twelve-year history of HCV infection was admitted due to locally advanced abdominal tumor involving the spleen and the left part of the diaphragm. Transaminase serum levels were not elevated. Neither peripheral lymphadenopathy nor bone marrow pathology was found. Absolute blood lymphocyte, erythrocyte and platelet counts were normal. A splenectomy with partial diaphragm resection in one block was performed. Recovery was uneventful. Pathologic examination with immunohistochemistry revealed SMZL and confirmed a neoplastic infiltration of the resected diaphragm. Following surgery, chemotherapy (CHOP regimen) and immunotherapy (anti-CD20 antibody) were given. At the last follow-up 15 months after surgery, the patient was free of any symptoms of lymphoma. Surgical resection of even locally advanced SMZL with involvement of adjacent tissues can be performed as a diagnostic and therapeutic procedure. Splenectomy is especially indicated in symptomatic patients without other sites of the disease. HCV infection may result in increased risk of SMZL due to the induction of B-cell lymphoproliferation. Because of possible lymphoma regression following anti-viral therapy, a systematic screening for HCV in patients with SMZL seems to be valuable and helpful for treatment planning.
C1 [Szynglarewicz, Bartlomiej] Lower Silesian Oncology Center, Department of Oncological Surgery, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Matkowski, Rafal] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
[Smorag, Zbigniew] Lower Silesian Oncology Center, Department of Oncological Surgery, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Forgacz, Jozef] Lower Silesian Oncology Center, Department of Oncological Surgery, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Pudelko, Marek] Lower Silesian Oncology Center, Department of Oncological Surgery, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Kornafel, Jan] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
RP Szynglarewicz, B (reprint author), Lower Silesian Oncology Center, Department of Oncological Surgery, 53-413 Wroclaw, Poland.
EM szynglarewicz.b@dco.com.pl
CR Arcaini L, Paulli M, Boveri E, Vallisa D, Bernuzzi P, Orlandi E, Incardona P, Brusamolino E, Passamonti F, Burcheri S, Schena C, Pascutto C, Cavanna L, Margini U, Lazzarino M: Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles. Cancer 100: 107-115, 2004
Carbonari M, Caprini E, Tedesco T, Mazzetta F, Tocco V, Casato M, Russo G, Fiorilli M: Hepatitis C virus drives the unconstrained monoclonal expansion of VH1-69-expressing memory B cells in type II cryoglobulinemia: a model of infection-driven lymphomagenesis. J Immunol 174: 6532-6539, 2005
Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Sandreau V, Delmas B, Valensi F, Cacoub P, Brechot C, Varet B, Troussard X: Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 347: 89-94, 2002
Iannitto E, Ambrosetti A, Ammatuna E, Colosio M., Florena AM, Tripodo C, Minardi V, Calvaruso G, Mitra ME, Pizzolo G, Menestrina F, Franco V: Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients. Cancer 101: 2050-2057, 2004
Kelaidi C, Rollot F, Park S, Tulliez M, Christoforov B, Calmus Y, Podevin P, Bouscary D, Sogni P, Blanche P, Dreyfus F: Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas. Leukemia 18: 1711-1716, 2004
Marasca R, Vaccari P, Luppi M, Zucchini P, Castelli I, Barozzi P, Cuoghi A, Torelli G: Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma. Am J Pathol 159: 253-261, 2001
Oscier D, Owen R, Johnson S: Splenic marginal zone lymphoma. Blood Rev 19: 39-51, 2005
Pitini V, Arrigo C, Righi M, Scaffidi M, Sturniolo G: Systematic screening for HCV infection should be performed in patients with splenic marginal zone lymphoma. Br J Haematol 124: 252-253, 2004
Svoboda J, Andreadis C, Downs LH, Miller Jr WT, Tsai DE, Schuster SJ: Regression of advanced non-splenic marginal zone lymphoma after treatment of hepatitis C virus infection. Leuk Lymphoma 46: 1365-1368, 2005
Weng WK, Levy S: Hepatitis C virus, HCV, and lymphomagenesis. Leuk Lymphoma 44: 1113-1120, 2003
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2007
VL 13
IS 4
BP 382
EP 384
PG 3
ER
PT J
AU Kopper, L
AF Kopper, Laszlo
TI Lapatinib: A Sword with Two Edges
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Lapatinib; Targeted therapy; EGFR-inhibition; HER2-inhibition; Trastuzumab resistance; Breast cancer
ID Lapatinib; Targeted therapy; EGFR-inhibition; HER2-inhibition; Trastuzumab resistance; Breast cancer
AB Lapatinib is an oral dual tyrosine kinase inhibitor targeting EGFR1 and EGFR2 (HER2). Phase I trials have shown that lapatinib is well tolerated, with mild diarrhea and skin rush as common adverse effects, and low cardiotoxicity. Phase II and III trials provided evidences on clinical effectiveness in advanced or metastatic breast cancer and potential against brain metastases. Lapatinib is active in combination with trastuzumab and in trastuzumab-resistant patients, moreover it has synergistic action with capecitabine. Several clinical trials are in progress to explore the effectiveness of lapatinib in other combinations and against several tumor types.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Bilancia D, Rosati G, Dinota A et al, 2007, Lapatinib in breast cancer. Ann Oncol 18(suppl 6):vi26–vi30
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Wood ER, Truesdale AT, Mc Donald OB et al, 2004, A unique structure for epidermal growth factor receptor bound to GW572016, lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 64:6652–6659
Xia W, Liu LH, Ho P, Spector NL, 2004, Truncated ErbB2 receptor, p95ErbB2, is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene 23:646–653
Rusnak DW, Lackey K, Affleck K et al, 2001, The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumorderived cell lines in vitro and in vivo. Mol Cancer Ther 1:85–94
Chu I, Blackwell K, Chen S, Slingerland J, 2005, The dual ErbB1/ ErbB2 inhibitor, lapatinib, GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res 65:18–25
Burris HA, Hurwitz HI, Dees C et al, 2005, Phase I safety, pharmacokinetics, and clinical activity study of lapatinib, GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases in heavily pretreated patients with metastatic carcinomas. J Clin Oncol 23:5305–5313
Blackwell KL, Burstein H, Pegram M, et al, 2005, Determining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancer. Proc Am Soc Clin Oncol 23:(abstr 3004)
Chu QSC, Schwartz G, de Bono J et al, 2007, Phase I and pharmacokinetic study of lapatinib in combination with capecitabine in patients with advanced malignancies. J Clin Oncol 25:3753–3758
Siegel-Lakhai WS, Beijnen JH, Vervenne WL et al, 2007, Phase I pharmacokinetic study of the safety and tolerability of lapatinib, GW572016, in combination with oxaliplatin/fluorouracil/ leucovorin, FOLFOX4, in patients with solid tumors. Clin Cancer Res 13:4495–4502
Midgley RS, Kerr DJ, Flaherty KT et al, 2007, A phase I and pharmacokinetic study of lapatinib in combination with infusional 5- fluorouracil, leucovorin and irinotecan. Ann Oncol 18:2025–2029
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL, 1987, Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235:177–182
Magnifico A, Albano L, Campaner S et al, 2007, Protein kinase C determines HER2 fate in breast carcinoma cells with HER2 protein overexpression without gene amplification. Cancer Res 67:5308–5317
Vogel CL, Cobleigh MA, Tripathy D et al, 2002, Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726
Hegde PS, Rusnak D, Bertiaux M, Alligood K, Strum J, Gagnon R, Gilmer TM, 2007, Delineation of molecular mechanisms of sensitivity to lapitinib in breast cancer cell lines using global gene expression profiles. Mol Cancer Ther 6:1629–1640
Moy B, Kirkpatrick P, Kar S, Goss P, 2007, Lapatinib. Nature Rev Drug Discovery 6:431–432
Xia W, Gerard CM, Liu L, Baudson NM, Ory TL, Spector NL, 2005, Combining lapatinib, GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene 24:6213–6221
Spector N, Liu L, Gerard C et al, 2005, Combining lapatinib, GW572016, with anti-erbB2 antibodies elicits synergistic apoptotic effects in erbB2 overexpressing breast cancer cells. J Clin Oncol 23, 16S, pt1), abstract 557
Konecny GE, Pegram MD, Venkatesan N et al, 2006, Activity of the dual kinase inhibitor lapatinib, GW572016, against HER-2 overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 66:1630–1639
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Geyer CE, Forster J, Lindquist D et al, 2006, Lapatinib plus capecitabine for HER2-positive advanced breast cancer. New Engl J Med 355:2733–2743
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Nahta R, Yuan LXH, Zhang B, Kobayashi R, Esteva FJ, 2005, Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 65:1118–1125
Nahta R, Yuan LXH, Du Y, Esteva FJ, 2007, Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Mol Cancer Ther 6:667–674
Xia W, Bacus S, Hegde P et al, 2006, A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci USA 103:7795–7800
DiGiovanna MP, Chakraborty A, 2006, Combinations of HER2, estrogen receptor, ER, and IGF-I receptor, IGF1R, inhibitors induce apoptosis in breast cancer cells: dramatic effects of HER2 inhibitors on non-overexpressing cells. Proc Am Assoc Cancer Res 47:1226
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 1
EP 8
DI 10.1007/s12253-008-9018-z
PG 8
ER
PT J
AU Kozakowski, N
Soleiman, A
Pammer, J
AF Kozakowski, Nicolas
Soleiman, Afschin
Pammer, Johannes
TI BMI-1 Expression is Inversely Correlated with the Grading of Renal Clear Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BMI-1; Renal cell carcinoma; Differentiation; Stem cell
ID BMI-1; Renal cell carcinoma; Differentiation; Stem cell
AB BMI-1 regulates cell proliferation and differentiation, is involved in stem cell maintenance and can act as an oncogene. We investigated BMI-1 expression in healthy normal kidney and in 77 renal tumours by immunohistochemistry, and correlated it with tumour differentiation. BMI-1 could regularly be demonstrated in distal tubules and in Bowman’s capsule, whereas it was mostly lacking in proximal tubules, indicating that it may rather be a differentiation marker of different renal cell populations than a stem cell marker. In contrast to previous studies demonstrating a correlation between BMI-1 expression and malignancy, we showed that its expression was inversely correlated with the differentiation grade of clear cell carcinoma. Furthermore, despite their different biologies, BMI-1 was strongly expressed in both papillary carcinomas and oncocytomas. Thus, in renal clear cell carcinomas BMI-1 is rather a differentiation marker lost in carcinomas with high malignancy than an oncogene involved in tumour progression.
C1 [Kozakowski, Nicolas] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1097 Vienna, Austria.
[Soleiman, Afschin] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1097 Vienna, Austria.
[Pammer, Johannes] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1097 Vienna, Austria.
RP Pammer, J (reprint author), Medical University of Vienna, Department of Pathology, 1097 Vienna, Austria.
EM johannes.pammer@meduniwien.ac.at
CR Jacobs JJ, Kieboom K, Marino S et al, 1999, The oncogene and Polycomb-group gene BMI-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397:164–168
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Kim JH, Yoon S, Kim CN et al, 2004, The BMI-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins. Cancer Lett 203:217–224
Liu S, Dontu G, Mantle ID et al, 2006, Hedgehog signaling and BMI-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66:6063–6071
Raaphorst F, 2003, Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene BMI-1. Trends Immunol 24:522–524
Muller J, Gaunt S, Lawrence PA, 1995, Function of the Polycomb protein is conserved in mice and flies. Development 121:2847– 2852
Lessard J, Schumacher A, Thorsteinsdottir U et al, 1999, Functional antagonism of the Polycomb-Group genes eed and BMI1 in hemopoietic cell proliferation. Genes Dev 13:2691–2703
Van Kemenade FJ, Raaphorst FM, Blokzijl T et al, 2001, Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 7:3896–3901
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Bea S, Tort F, Pinyol M et al, 2001, BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res 61:2409–2412
Kim JH, Yoon S, Jeong SH et al, 2004, Overexpression of BMI-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast 13:383–388
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Sagrinati C, Netti G, Mazzinghi B et al, 2006, Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys. J Am Soc Nephrol 17: 2443– 2456
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 9
EP 13
DI 10.1007/s12253-008-9006-3
PG 5
ER
PT J
AU Szabo, E
Korpos,
Batmunkh, E
Lotz, G
Holczbauer,
Kovalszky, I
Deak, F
Kiss, I
Schaff, Zs
Kiss, A
AF Szabo, Erzsebet
Korpos, Eva
Batmunkh, Enkhjargal
Lotz, Gabor
Holczbauer, Agnes
Kovalszky, Ilona
Deak, Ferenc
Kiss, Ibolya
Schaff, Zsuzsa
Kiss, Andras
TI Expression of Matrilin-2 in Liver Cirrhosis and Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Matrilin-2; Basement membrane; Extracellular matrix; Hepatocellular carcinoma; Cirrhosis
ID Matrilin-2; Basement membrane; Extracellular matrix; Hepatocellular carcinoma; Cirrhosis
AB The recently described matrilin protein family is part of the extracellular matrix, their pathophysiological role as well as distribution in liver diseases, however, have not yet been studied. Considering that matrilins have been found to play role in cell growth and tissue remodeling, their possible involvement in carcinogenesis has been raised. The main objective of this study was to investigate the changes in matrilin-2 expression which is one of the main components of basement membranes. Thirty-five cases of surgically resected hepatocellular carcinomas, 35 corresponding surrounding liver tissues and 10 normal liver samples were used for the study. In 15 of 35 cases the tumor developed on the basis of cirrhosis. Matrilin-2 protein expression was detected in normal liver around bile ducts, portal blood vessels, while sinusoids were negative by immunohistochemistry. Cirrhotic surrounding tissue showed intensive matrilin-2 staining along the sinusoids. Tumorous neovasculature was found strongly positive by immunohistochemistry. No differences, however, were detected by morphometry regarding the amount of protein expression based on the grade of hepatocellular carcinomas. Real-time RT-PCR did not show significant differences in matrilin-2 mRNA expression between normal, cirrhotic and tumor samples. This suggests posttranslational modification of matrilin-2 manifesting in altered distribution in liver fibrosis. Our data indicate that matrilin-2 is a novel basement membrane component in the liver, which is synthetized during sinusoidal "capillarization" in cirrhosis and in hepatocellular carcinoma. This is the first report to describe the expression and distribution of matrilin-2 in human normal and cirrhotic liver as well as in hepatocellular carcinoma.
C1 [Szabo, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Korpos, Eva] University of Szeged, Department of Medical ChemistrySzeged, Hungary.
[Batmunkh, Enkhjargal] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Holczbauer, Agnes] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Deak, Ferenc] University of Szeged, Department of Medical ChemistrySzeged, Hungary.
[Kiss, Ibolya] University of Szeged, Department of Medical ChemistrySzeged, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Monto A, Wright TL, 2001, The epidemiology and prevention of hepatocellular carcinoma. Semin Oncol 28:441–449
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Deak F, Wagener R, Kiss I, Paulsson M, 1999, The matrilins: a novel family of oligomeric extracellular matrix proteins. Matrix Biol 18:55–64
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Batmunkh E, Tatrai P, Szabo E, Lodi Cs, Holczbauer A, Paska Cs, Kupcsulik P, Kiss A, Schaff Zs, Kovalszky I, 2007, Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 38:1508–1515
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 15
EP 22
DI 10.1007/s12253-008-9005-4
PG 8
ER
PT J
AU Appel, LMM
Edelweiss, IM
Fleck, J
Rivero, FL
Rivoire, AW
Monego, IH
dos Reis, R
AF Appel, L M Marcia
Edelweiss, I Maria
Fleck, James
Rivero, F Luis
Rivoire, A Waldemar
Monego, I Heleusa
dos Reis, Ricardo
TI p53 and BCL-2 as Prognostic Markers in Endometrial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; p53; BCL-2; Prognosis
ID Endometrial cancer; p53; BCL-2; Prognosis
AB The objective of this study was to verify the frequency of p53 and BCL-2 immunohistochemical expression in patients with endometrial carcinoma and to correlate it with histological factors (histological type, tumor grade, depth of myometrial invasion, lymph node involvement and surgical staging) and survival. Forty-eight patients with endometrial carcinoma who were submitted to primary surgical treatment were assessed. p53 and BCL-2 immunohistochemical expression was determined using paraffin blocks containing the tumor area. p53 and BCL-2 expression was detected in 39.6% and 58.3% of the tumors, respectively. No significant difference was found regarding the frequency of p53 expression when analyzing histological type (33.3% in endometrioid tumors, 58.3% in non-endometrioid tumors; p=0.176), depth of myometrial invasion (p=0.632) and surgical staging (I—11.1%, II—66.7%, III—57.1%; p=0.061). p53 expression was significantly more frequent in undifferentiated tumors (p=0.007) and in those showing lymph node involvement (p=0.030). Univariate analysis showed a positive association with death (RR, 3.358; CI, 1.386–8.134; p=0.005) and short-term survival. The present study did not reveal any correlation between BCL-2 expression and histopathologic markers or survival. In conclusion, this study showed that p53 expression is directly correlated with undifferentiated tumors, lymph-node involvement and risk of death. On the other hand, BCL-2 expression was not correlated with any known histological factors.
C1 [Appel, L M Marcia] Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Gynecology and Obstetrics, Rua Comendador Caminha, 128/902, CEP 90430-030 Porto Alegre, Rio Grande do Sul, Brazil.
[Edelweiss, I Maria] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, Rio Grande do Sul, Brazil.
[Fleck, James] Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Clinical OncologyPorto Alegre, Rio Grande do Sul, Brazil.
[Rivero, F Luis] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, Rio Grande do Sul, Brazil.
[Rivoire, A Waldemar] Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Gynecology and Obstetrics, Rua Comendador Caminha, 128/902, CEP 90430-030 Porto Alegre, Rio Grande do Sul, Brazil.
[Monego, I Heleusa] Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Gynecology and Obstetrics, Rua Comendador Caminha, 128/902, CEP 90430-030 Porto Alegre, Rio Grande do Sul, Brazil.
[dos Reis, Ricardo] Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Gynecology and Obstetrics, Rua Comendador Caminha, 128/902, CEP 90430-030 Porto Alegre, Rio Grande do Sul, Brazil.
RP Appel, LMM (reprint author), Medical Post-Graduate Program, School of Medicine, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Department of Gynecology and Obstetrics, CEP 90430-030 Porto Alegre, Brazil.
EM marciaappel@terra.com.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 23
EP 30
DI 10.1007/s12253-008-9000-9
PG 8
ER
PT J
AU Herszenyi, L
Sipos, F
Galamb, O
Solymosi, N
Hritz, I
Miheller, P
Berczi, L
Molnar, B
Tulassay, Zs
AF Herszenyi, Laszlo
Sipos, Ferenc
Galamb, Orsolya
Solymosi, Norbert
Hritz, Istvan
Miheller, Pal
Berczi, Lajos
Molnar, Bela
Tulassay, Zsolt
TI Matrix Metalloproteinase-9 Expression in the Normal Mucosa–Adenoma–Dysplasia–Adenocarcinoma Sequence of the Colon
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenoma; Colorectal cancer; Dysplasia; Matrix metalloproteinase 9; Polymerase chain reaction
ID Adenoma; Colorectal cancer; Dysplasia; Matrix metalloproteinase 9; Polymerase chain reaction
AB It has been proposed that matrix metalloproteinases (MMPs) play a role in tumor invasion. We determined protein expression of matrix metalloproteinase-9 (MMP-9) in colorectal cancer (CRC), corresponding normal mucosa and colorectal adenomas. For confirmation of immunohistochemical results MMP-9 TaqMan RT-PCR analysis was performed. Expression of MMP-9 was determined on paraffin embedded biopsy sections by immunohistochemistry in 31 CRC patients (from cancer tissue and corresponding normal mucosa) and in 30 patients with adenoma (nine adenomas with high grade of dysplasia). MMP-9 immunostaining was determined semiquantitatively. For Taqman RT-PCR analyses normal mucosa (n=5), adenoma without (n=6) and with high grade dysplasia (n=7) and CRC (n=10) were investigated. Statistical analysis with ANOVA, LSD test and correlation analysis were performed. P value of <0.05 was considered significant. The MMP-9 expression in CRC was significantly higher compared to adenomas or the normal mucosa (P=0.001). Significantly higher expression of MMP-9 has been observed in adenomas with high grade dysplasia compared to other adenomas or normal colon (P<0.001). Diffuse strong MMP-9 expression was present in tumor as well as in stromal cells. In adenoma samples, dysplastic epithelial cells showed moderate intensive cytoplasmic MMP-9 expression, with a clear-cut differentiation between dysplastic and nondysplastic areas. Staining intensity correlated with the grade of CRC. We demonstrate a significantly higher expression of MMP-9 in adenoma with high grade dysplasia—CRC sequence as compared to normal tissue. The over-expression of MMP-9 strongly suggests its association with colorectal carcinogenesis.
C1 [Herszenyi, Laszlo] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Solymosi, Norbert] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Hritz, Istvan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Miheller, Pal] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Berczi, Lajos] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, 1088 Budapest, Hungary.
RP Herszenyi, L (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM hersz@bel2.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 31
EP 37
DI 10.1007/s12253-008-9004-5
PG 7
ER
PT J
AU Hiraishi, Y
Wada, T
Nakatani, K
Tojyo, I
Matsumoto, T
Kiga, N
Negoro, K
Fujita, Sh
AF Hiraishi, Yukihiro
Wada, Takeshi
Nakatani, Ken
Tojyo, Itaru
Matsumoto, Takashi
Kiga, Norifumi
Negoro, Kenji
Fujita, Shigeyuki
TI EGFR Inhibitor Enhances Cisplatin Sensitivity of Oral Squamous Cell Carcinoma Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epidermal growth factor receptor (EGFR); EGFR inhibitor; Oral squamous cell carcinoma (OSCC); Cisplatin-resistant OSCC cell line; Cisplatin sensitivity and resistance
ID Epidermal growth factor receptor (EGFR); EGFR inhibitor; Oral squamous cell carcinoma (OSCC); Cisplatin-resistant OSCC cell line; Cisplatin sensitivity and resistance
AB Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.
C1 [Hiraishi, Yukihiro] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Wada, Takeshi] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Nakatani, Ken] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Tojyo, Itaru] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Matsumoto, Takashi] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Kiga, Norifumi] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Negoro, Kenji] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
[Fujita, Shigeyuki] Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 811-1 Kimiidera, 641-8509 Wakayama, Japan.
RP Hiraishi, Y (reprint author), Wakayama Medical University, Department of Oral and Maxillofacial Surgery, 641-8509 Wakayama, Japan.
EM hiraishi@wakayama-med.ac.jp
CR Salomon DS, Brandt R, Ciardiello F et al, 1995, Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 39
EP 43
DI 10.1007/s12253-008-9020-5
PG 5
ER
PT J
AU Khademi, B
Razmkhah, M
Erfani, N
Gharagozloo, M
Ghaderi, A
AF Khademi, Bijan
Razmkhah, Mahboobeh
Erfani, Nasrollah
Gharagozloo, Marjan
Ghaderi, Abbas
TI SDF-1 and CCR5 Genes Polymorphism in Patients with Head and Neck Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck cancer; SDF-1; CCR5; Polymorphism; Metastasis
ID Head and neck cancer; SDF-1; CCR5; Polymorphism; Metastasis
AB The frequency of SDF1–3′A and CCR5Δ32 in patients with head and neck cancer were determined in this study. The frequencies of alleles and genotypes of SDF-1 and CCR5 were assessed by PCR method in 156 patients with malignant head and neck cancer, 125 (80.1%) cases with squamous cell carcinoma and 31 (19.9%) cases with salivary gland tumors and compared with 262 age–sex matched healthy control individuals. SDF-1 genotypes in patients with SCC of head and neck, but not with salivary gland tumors, showed a statistically significant difference compared to the normal group (P<0.005 for SCC and P=0.3 for salivary gland tumors). There were no significant differences in the frequencies of SDF1–3′A allele, CCR5 genotypes and alleles between patients and controls. Based on the present study SDF1–3́A may be associated with the susceptibility of patients to SCC of head and neck cancer.
C1 [Khademi, Bijan] Shiraz University of Medical Sciences, Department of ENTShiraz, Iran.
[Razmkhah, Mahboobeh] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Erfani, Nasrollah] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Gharagozloo, Marjan] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Razmkhah, M (reprint author), Shiraz University of Medical Sciences, Institute for Cancer Research, Shiraz, Iran.
EM razmkhahm@sums.ac.ir
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 45
EP 50
DI 10.1007/s12253-008-9007-2
PG 6
ER
PT J
AU Kamory, E
Olasz, J
Csuka, O
AF Kamory, Eniko
Olasz, Judit
Csuka, Orsolya
TI Somatic APC Inactivation Mechanisms in Sporadic Colorectal Cancer Cases in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Allelic imbalance; APC; Mutation; Promoter hypermethylation; Sporadic colorectal cancer
ID Allelic imbalance; APC; Mutation; Promoter hypermethylation; Sporadic colorectal cancer
AB The role of germline inactivation of the adenomatosis polyposis coli (APC) gene in hereditary colorectal cancer is well known, being the most important cause of familial adenomatous polyposis (FAP) syndrome. Hereditary cases with germline mutations, however, account only for 5–10% of colorectal cancers. The somatic inactivation of this gene has also been observed in sporadic cases. In order to examine the inactivation mechanisms of the APC gene we screened 70 sporadic colorectal cancer cases (27 rectal, 43 intestinal) of different stages for promoter hypermethylation, allelic imbalance (AI) and somatic mutations. The presence of promoter hypermethylation was observed in 21 cases (30%). Fifteen of the examined tumors (21%) showed AI, and also 15 tumors (21%) carried at least one somatic mutation. Thirteen of the detected alterations were novel variations: seven frameshifts, four missense mutations and two polymorphisms. Biallelic inactivation was found in 15 patients (21%). These results suggest that the inactivation of the APC gene is very common in sporadic colorectal cancer, and the main inactivation mechanism of the APC gene is promoter hypermethylation. Allelic imbalance has the same frequency as mutations, and mutations in the APC gene are more common in the early stages and in tumors located in the rectum.
C1 [Kamory, Eniko] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Olasz, Judit] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Csuka, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
RP Kamory, E (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, H-1122 Budapest, Hungary.
EM eniko.kamory@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 51
EP 56
DI 10.1007/s12253-008-9019-y
PG 6
ER
PT J
AU Kato, K
Kawashiri, Sh
Tanaka, A
Noguchi, N
Nakaya, H
Hase, T
Yamamoto, E
AF Kato, Koroku
Kawashiri, Shuichi
Tanaka, Akira
Noguchi, Natsuyo
Nakaya, Hiromitsu
Hase, Takashi
Yamamoto, Etsuhide
TI Predictive Value of Measuring p53 Labeling Index at the Invasive Front of Oral Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Invasive front; p53; Labeling index
ID Oral squamous cell carcinoma; Invasive front; p53; Labeling index
AB Many studies have revealed the frequency of p53 abnormalities in oral cancer. However, it reports only on the relation between clinicopathological findings and p53 expression, and there is no study to examine the relation to the p53 labeling index (p53-LI). The purposes of this study were to examine the correlation between p53 labeling index (p53-LI) at the invasive front of oral squamous cell carcinomas (OSCC) and clinicopathological findings by immunohistochemical staining, and to evaluate clinical significance of measuring p53-LI at the invasive front of OSCC. Sixty-six biopsy specimens of OSCC were randomly selected. Patient age, gender, primary sites, T category, N category, degree of differentiation and mode of cancer invasion were analyzed. p53 expression did not correlate significantly with the clinical findings. However, significant differences were found between p53-LI and the degree of cell differentiation (p<0.05). The p53-LI of highgrade invasive tumors was significantly larger than that of low-grade invasive tumors (p<0.05). The overall survival rate (OS) among low-scoring p53-LI cases was 75.5% whereas that for high-scoring p53-LI cases was 40.6%. The disease-free survival rate (DFS) among low-scoring p53-LI cases was 39.5% whereas that for high-scoring p53-LI cases was 76.1%. Patients with low-scoring p53-LI had a significantly worse prognosis than those with among highscoring p53-LI (p<0.05). Consequently, the measurement of p53-LI at the invasive front of OSCC is significant as one of the indicators of prognosis.
C1 [Kato, Koroku] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Kawashiri, Shuichi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Tanaka, Akira] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Noguchi, Natsuyo] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Nakaya, Hiromitsu] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Hase, Takashi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
[Yamamoto, Etsuhide] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Japan.
RP Kato, K (reprint author), Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 920-8640 Kanazawa, Japan.
EM k-koroku@oral.m.kanazawa-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 57
EP 61
DI 10.1007/s12253-008-9022-3
PG 5
ER
PT J
AU Eros, N
Karolyi, Zs
Marschalko, M
Karpati, S
Matolcsy, A
AF Eros, Nora
Karolyi, Zsuzsanna
Marschalko, Marta
Karpati, Sarolta
Matolcsy, Andras
TI Clinical, Histopathological, Immunophenotypic and Molecular Analysis of 60 Patients with Cutaneous T-cell Infiltrates with Follow up of Indeterminate Cases to Identify T-cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cutaneous T-cell lymphoma; Mycosis fungoides; Cutaneous T-cell infiltrate; Histopathology; Immunophenotype; Molecular biology
ID Cutaneous T-cell lymphoma; Mycosis fungoides; Cutaneous T-cell infiltrate; Histopathology; Immunophenotype; Molecular biology
AB Diagnosis of primary cutaneous T-cell lymphomas, especially of mycosis fungoides could be difficult in early stage due to clinical and histopathological similarity to reactive inflammatory dermatoses. To assess diagnostic value of complex histological, immunophenotypic and Tcell receptor γ gene rearrangement analysis, skin biopsy specimen and peripheral blood samples of 60 patients with suspected cutaneous T-cell lymphoma were analyzed. Our results indicate clear distinction between reactive dermatoses (benign cases, n=31) and cutaneous T-cell lymphomas (lymphoma cases, n=17). As definite diagnosis was not obtained in a smaller group of patients (indeterminate cases, n=12), these patients were followed up. Repeated skin biopsy confirmed mycosis fungoides in 6/12 cases, however in 6/12 patients the diagnosis remained indeterminate. We concluded that careful and complex clinical follow up and repeated histopathological, immunophenotypic and molecular analysis is needed for an appropriate diagnosis in the assessment of early stage mycosis fungoides and uncertain clinical cases.
C1 [Eros, Nora] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria str. 41, 1085 Budapest, Hungary.
[Karolyi, Zsuzsanna] Semmelweis Hospital, Department of DermatologyMiskolc, Hungary.
[Marschalko, Marta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria str. 41, 1085 Budapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria str. 41, 1085 Budapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Eros, N (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM dr.eros@citromail.hu
CR Bachelez H, 1999, The clinical use of molecular analysis of clonality in cutaneous lymphocytic infiltrates. Arch Dermatol 135:200–202
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Burg G, Kempf W, Dummer R, 2001, Diagnostic signs of cutaneous lymphomas. J Eur Acad Dermatol Venereol 15:358–360
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Flaig MJ, Schuhmann K, Sander CA, 2000, Impact of molecular analysis in the diagnosis of cutaneous lymphoid infiltrates. Semin Cutan Med Surg 19:87–90
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 63
EP 67
DI 10.1007/s12253-008-9014-3
PG 5
ER
PT J
AU Nagy, CsA
Cserep, Zs
Tolnay, E
Nagykalnai, T
Forster, T
AF Nagy, Csaba Andras
Cserep, Zsuzsanna
Tolnay, Edina
Nagykalnai, Tamas
Forster, Tamas
TI Early Diagnosis of Chemotherapy-induced Cardiomyopathy: a Prospective Tissue Doppler Imaging Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anthracycline; Tissue Doppler imaging; Cardiotoxicity
ID Anthracycline; Tissue Doppler imaging; Cardiotoxicity
AB The aim of our study was to compare the applicability of the conventional echocardiography and a novel method, tissue Doppler imaging (TDI) in detection of late or subclinical cardiotoxicity following anthracycline chemotherapy in long-term follow up. Forty women (31 to 65 years) were enrolled, who had not received anthracyclines previously and had normal cardiac function. The control group consisted of 20 healthy persons of similar age range. In addition to standard echocardiographic measurements, each patient underwent specific measurements (Eseptum separation, pulmonary venous flow) as well. Furthermore, the myocardial velocity of numerous segments of the mitral anulus obtained with pulsed wave TDI was also detected over a two-year-long period. Systolic left ventricular function did not change significantly either in the study or in the control group. After one year, diastolic left ventricular function was impaired in 39 patients (97.5%), and 29 (72.5%) of these showed clear changes by means of the traditional E/A ratio and TDI. However, in ten patients (25%) the diastolic dysfunction could only be detected with TDI. At the end of the study diastolic dysfunction was detected in each patient, but in 13 patients (32.5%) the relaxation disorder could be revealed only with TDI. Detectable myocardial damage occurred in the study group as a result of anthracycline therapy. Our results confirmed our assumptions that TDI is a more precise and useful examination method than the traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.
C1 [Nagy, Csaba Andras] Uzsoki Municipal Hospital, 1st Department of Internal Medicine and Cardiology, Uzsoki u. 29, H-1145 Budapest, Hungary.
[Cserep, Zsuzsanna] Semmelweis UniversityBudapest, Hungary.
[Tolnay, Edina] Pest County Institute of Pulmonology, 2nd DepartmentTorokbalint, Hungary.
[Nagykalnai, Tamas] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Forster, Tamas] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
RP Nagy, CsA (reprint author), Uzsoki Municipal Hospital, 1st Department of Internal Medicine and Cardiology, H-1145 Budapest, Hungary.
EM nagycsaba@uzsoki.hu
CR Alam M, Wardell J, Andersson E, Samad BA, Nordlander R, 2000, Effects of first myocardial infarction on left ventricular systolic and diastolic function with the use of mitral annular velocity determined by pulsed wave Doppler tissue imaging. J Am Soc Echocardiogr 13:343–352
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 69
EP 77
DI 10.1007/s12253-008-9013-4
PG 9
ER
PT J
AU Camlica, H
Duranyildiz, D
Oguz, H
Oral, NE
Yasasever, V
AF Camlica, Hakan
Duranyildiz, Derya
Oguz, Hilal
Oral, Nezih Ethem
Yasasever, Vildan
TI The Diagnostic Value of Macrophage Migration Inhibitory Factor (MIF) in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MIF. CEA; CA 19-9; Tumor markers; Gastric cancer; Accuracy
ID MIF. CEA; CA 19-9; Tumor markers; Gastric cancer; Accuracy
AB The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum MIF, CEA, CA 19-9 levels and their various combinations in patients with gastric cancer. Study group consists of pathologically verified, gastric cancer (n=63) and apparently healthy controls (n=50). Serum MIF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum values of patients were significantly higher than the controls (p=0.011). Diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their various combinations. The best results were achieved with the marker combination of MIF–CEA–CA 19-9 and MIF–CEA combination. In our opinion, the combination of the markers MIF–CEA is a valuable diagnostic tool for gastric cancer.
C1 [Camlica, Hakan] University of Istanbul, Institute of Oncology, Preventive Oncology, Biostatistics and Epidemiology, Capa, 34390 Istanbul, Turkey.
[Duranyildiz, Derya] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Oguz, Hilal] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Oral, Nezih Ethem] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
[Yasasever, Vildan] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
RP Camlica, H (reprint author), University of Istanbul, Institute of Oncology, Preventive Oncology, Biostatistics and Epidemiology, 34390 Istanbul, Turkey.
EM hcamlica@istanbul.edu.tr
CR Correa P, 1992, Human gastric carcinogenesis: a multistep and multifactorial process. Cancer Res 52:6735–6470
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He XX, Yang J, Ding YWet al, 2006, Increased epithelial and serum expression of migration inhibitory factor, MIF, in gastric cancer: potential role of MIF in gastric carcinogenesis. Gut 55:797–802
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 79
EP 83
DI 10.1007/s12253-008-9002-7
PG 5
ER
PT J
AU Nemes, AJ
Redl, P
Boda, R
Kiss, Cs
Marton, JI
AF Nemes, A Judit
Redl, Pal
Boda, Robert
Kiss, Csongor
Marton, J Ildiko
TI Oral Cancer Report from Northeastern Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral cancer; Squamous cell carcinoma; Survival; Northeastern Hungary
ID Oral cancer; Squamous cell carcinoma; Survival; Northeastern Hungary
AB In Hungary oral and pharyngeal cancers have been reported the fourth most common malignancy in males and the sixth for both sexes. The aim of the present study was to characterize oral squamous cell carcinoma (OSCC) patients in Northeastern Hungary. 119 randomly selected patients with OSCC were included in the study. Epidemiological data, clinicopathological parameters and the risk factors were registered. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients was diagnosed with early stage (I–II) lesions and moderately differentiated tumors. The 5-year overall survival rate was 38.7%. There was a significant correlation between survival and tumor size, lymph node involvement and clinical stage. At the time of diagnosis 65.5% of the patients were smokers. Smoking significantly correlated with younger age, male gender, advanced clinical stages and alcohol consumption. 75.5% of the patients consumed alcohol, 41.1% of them exceeding the conventional amount regularly. Drinking habit significantly correlated with younger age, male gender and tumor site i.e. gingiva, retromolar region, tongue. The dental status was acceptable only in 12.6% of the cases. There was a significant correlation between dental status and age, smoking and drinking habits. Clinical stage has the most significant impact on survival and the most important high-risk habits in Northeastern Hungary are smoking and alcohol consumption. Therefore, early detection and treatment, cessation of tobacco and alcohol abuse, and a regular dental care may improve patients’ survival in the region.
C1 [Nemes, A Judit] University of Debrecen, Faculty of Dentistry, Nagyerdei krt. 98., 4012 Debrecen, Hungary.
[Redl, Pal] University of Debrecen, Faculty of Dentistry, Nagyerdei krt. 98., 4012 Debrecen, Hungary.
[Boda, Robert] University of Debrecen, Faculty of Dentistry, Nagyerdei krt. 98., 4012 Debrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Nagyerdei krt. 98., 4012 Debrecen, Hungary.
[Marton, J Ildiko] University of Debrecen, Faculty of Dentistry, Nagyerdei krt. 98., 4012 Debrecen, Hungary.
RP Nemes, AJ (reprint author), University of Debrecen, Faculty of Dentistry, 4012 Debrecen, Hungary.
EM nemesj@dote.hu
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Lockhart PB, Norris CMJr, Pulliam C, 1998, Dental factors in the genesis of squamous cell carcinoma of the oral cavity. Oral Oncol 34:133–139
Moreno-Lopez LA, Esparza-Gomez GC, Gonzalez-Navarro A et al, 2000, Risk of oral cancer associated with tobacco smoking, alcohol consumption and oral hygiene: a case-control study in Madrid, Spain. Oral Oncol 36:170–174
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Homann N, Tillonen J, Rintamaki H et al, 2001, Poor dental status increases acetaldehyde production from ethanol in saliva: a possible link to increased oral cancer risk among heavy drinkers. Oral Oncol 37:153–158
de Visscher JGAM, Schaapveld M, Otter R et al, 1998, Epidemiology of cancer of the lip in the Netherlands. Oral Oncol 34:421–426
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 85
EP 92
DI 10.1007/s12253-008-9021-4
PG 8
ER
PT J
AU Bognar, G
Istvan, G
Bereczky, B
Ondrejka, P
AF Bognar, Gabor
Istvan, Gabor
Bereczky, Biborka
Ondrejka, Pal
TI Detection of Human Papillomavirus Type 16 in Squamous Cell Carcinoma of the Colon and Its Lymph Node Metastases with PCR and Southern Blot Hybridization
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Human papillomavirus; HPV; Squamous cell cancer; Colon cancer; PCR; Southern blot hybridization
ID Human papillomavirus; HPV; Squamous cell cancer; Colon cancer; PCR; Southern blot hybridization
AB The etiological role of human papillomavirus (HPV) in a number of squamous malignant tumors is well known. Squamous cell carcinoma (SCC) of colon is a rare disease with uncertain etiology. Our objective was to detect possible HPV infection in a colon SCC patient. The 94-year-old female patient was operated due to colon tumor causing passage disturbances. Histology confirmed SCC. Tumor tissue and the removed lymph nodes were examined with polymerase chain reaction and Southern blot hybridization techniques. Of HPV types most often occurring in malignant tumors (16, 18) the presence of HPV type 16 could be confirmed in the primary tumor and in four out of the nine surrounding lymph nodes, of which two were metastatic. HPV-16 infection could be detected in an SCC patient in the primary tumor and in surrounding lymph nodes. According to our knowledge, no similar study has been published yet.
C1 [Bognar, Gabor] Semmelweis University, 2nd Department of Surgery, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Istvan, Gabor] Semmelweis University, 2nd Department of Surgery, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Bereczky, Biborka] Semmelweis University, 2nd Department of Surgery, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Ondrejka, Pal] Semmelweis University, 2nd Department of Surgery, Kutvolgyi ut 4, 1125 Budapest, Hungary.
RP Bognar, G (reprint author), Semmelweis University, 2nd Department of Surgery, 1125 Budapest, Hungary.
EM bgabor@kut.sote.hu;bgbgbg@freemail.hu
CR McMurray HR, Hguyen D, Westbrook TF, McAnce DJ, 2001, Biology of human papilloma viruses. Int J Exp Pathol 82:15–33
Mantovani F, Banks L, 2001, The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20:7677–7685
Nguyen DX, Westbrook TF, McCance DJ, 2002, Human papilloma virus type 16 E7 maintains elevated levels of cdc25A tyrosone phosphatase during deregulation of cell cycle arrest. J Virol 76:619–632
Syrjanen KJ, 2002, HPV infection and oesophageal cancer. J Clin Pathol 55:721–728
Perez LO, Abba MC, Laguens RM, Golijov CD, 2005, Analysis of adenocarcinoma of the colon and rectum: detection of human papillomavirus, HPV, DNA by polymerase chain reaction. Colorectal Dis 7:492–495
Bodaghi S, Yamanegi K, Xiao SY, et al, 2005, Colorectal papillomavirus infection in patients with colorectal cancer. Clin Cancer Res 11:2862–2867
Buyru N, Budak N, Yazici M, Dalay N, 2003, p53 gene mutations are rare in human papillomavirus-associated colon cancer. Oncol Rep 10:2089–2092
Michelassi F, Mishlove LA, Stipa F, Block GE, 1988, Squamous cell carcinoma of the colon: Experience at University of Chicago, review of the literature, report of two cases. Dis Colon Rectum 31:228–235
Sotlar K, Koveker G, Aepinus C, et al, 2001, Human papilloma virus type 16 associated primary squamous cell carcinoma of the rectum. Gastroenterology 120:1046–1048
Audeau A, Han HW, Johnston MJ, et al, 2002, Does human papilloma virus have a role in squamous cell carcinoma of the colon and upper rectum? Eur J Surg Oncol 28:657–660
Bognar G, Imdahl A, Ledniczky G, Ondrejka P, 2006, A HPV infekcio lehetseges prediktiv szerepe a nyelocsorakos betegek neoadjuvans terapiara adott remissziojaban. Magyar Sebeszet 59:97–104
Southern EM, 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503– 517
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Cheng JY, Sheu LF, Meng CL, et al, 1995, Detection of human papilloma virus DNA in colorectal carcinoma by polymerase chain reaction. Gut 37:87–90
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Shah KV, Daniel RW, Simons JW, Vogelstein B, 1992, Investigation of colon cancer for human papillomavirus genomic sequences by polymerase chain reaction. J Clin Oncol 51:5–7
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Fule T, Csapo Z, Mathe M, et al, 2006, Prognostic significance of high-risk HPV status in advanced cervical cancers and pelvic lymph nodes. Gynecol Oncol 100:570–578
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 93
EP 96
DI 10.1007/s12253-008-9011-6
PG 4
ER
PT J
AU Ergin, H
Yildirim, B
Dagdeviren, E
Yagci, B
Ozen, F
Sen, N
Duzcan, E
AF Ergin, Hacer
Yildirim, Basak
Dagdeviren, Erol
Yagci, Baki
Ozen, Fatih
Sen, Nilay
Duzcan, Ender
TI A Prenatally Detected Case of Congenital Hepatoblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatoblastoma; Prenatal diagnosis; Ultrasound
ID Hepatoblastoma; Prenatal diagnosis; Ultrasound
AB Hepatoblastoma is a rare tumor of childhood and its incidence in the first year of life is about one in a million. Forty-two congenital hepatoblastoma cases were reported so far. Among 42 congenital hepatoblastoma patients, only seven cases have been detected in the prenatal period. Here we report a rare case diagnosed before birth and confirmed by postmortem autopsy.
C1 [Ergin, Hacer] Pamukkale University, Faculty of Medicine, Department of PediatricsDenizli, Turkey.
[Yildirim, Basak] Pamukkale University, Faculty of Medicine, Department of Obstetrics and GynecologyDenizli, Turkey.
[Dagdeviren, Erol] Pamukkale University, Faculty of Medicine, Department of PediatricsDenizli, Turkey.
[Yagci, Baki] Pamukkale University, Faculty of Medicine, Department of RadiologyDenizli, Turkey.
[Ozen, Fatih] Ege Hospital, Department of PediatricsDenizli, Turkey.
[Sen, Nilay] Pamukkale University, Faculty of Medicine, Department of PathologyDenizli, Turkey.
[Duzcan, Ender] Pamukkale University, Faculty of Medicine, Department of PathologyDenizli, Turkey.
RP Duzcan, E (reprint author), Pamukkale University, Faculty of Medicine, Department of Pathology, Denizli, Turkey.
EM eduzcan@pau.edu.tr
CR Shih JC, Tsao PN, Huang SF, Yen BL, Lin JH, Lee CN, Hsieh FJ, 2000, Antenatal diagnosis of congenital hepatoblastoma in utero. Ultrasound Obstet Gynecol 16:94–97
Ammann RA, Plaschkes J, Leibundgut K, 1999, Congenital hepatoblastoma: a distinct entity. Med Pediatr Oncol 32:466–468
Woodward PJ, Sohaey R, Kennedy A, Koeller KK, 2005, From the archives of the AFIP: a comprehensive review of fetal tumors with pathologic correlation. Radiographics 25:215–242
Finegold MJ, 1991, Liver tumors. In: Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB, ed, Pediatric gastrointestinal disease: pathophysiology, diagnosis, management. B. C. Decker, Hamilton, 914–926
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Dehner LP, 1978, Hepatic tumors in the pediatric age group: a distinctive clinicopathologic spectrum. In: Rosenberg HS, Bolande RP, eds, Perspective in pediatric pathology. Year Book, Chicago, 27–68
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McNamara A, Levine D, 2005, Intraabdominal fetal echogenic masses: a practical guide to diagnosis and management. Radiographics 25:633–645
Ohishi H, Hirai T, Yamada R, Hirohashi S, Uchida H, Hashimoto H, Jibiki T, Takeuchi Y, 1998, Three-dimensional power Doppler sonography of tumor vascularity. J Ultrasound Med 17:619–622
Miller JH, Greenspan BS, 1985, Integrated imaging of hepatic tumors in childhood. Part II. Benign lesions, congenital, reperative, and inflammatory). Radiology 154:91–100
Foucar E, Williamson RA, Yiu-Chiu V, Varner MW, Kay BR, 1983, Mesenchymal hamartoma of the liver identified by fetal sonography. Am J Roentgenol 140:970–972
Gonen R, Fong K, Chiasson DA, 1989, Prenatal sonographic diagnosis of hepatic hemangioendothelioma with secondary nonimmune hydrops fetalis. Obstet Gynecol 73:485–487
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Weinberg AG, Finegold MJ, 1983, Primary hepatic tumors of childhood. Hum Pathol 14:512–537
Von Schweinitz D, Gluer S, Mildenberger H, 1995, Liver tumors in neonates and very young infants: diagnostic pitfalls and therapeutic problems. Eur J Pediatr Surg 5:72–76
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 97
EP 100
DI 10.1007/s12253-008-9001-8
PG 4
ER
PT J
AU Horvath, FI
Szanto, A
Csiki, Z
Szodoray, P
Zeher, M
AF Horvath, Fanny Ildiko
Szanto, Antonia
Csiki, Zoltan
Szodoray, Peter
Zeher, Margit
TI Intrapulmonary Rheumatoid Nodules in a Patient with Long-Standing Rheumatoid Arthritis Treated with Leflunomide
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intrapulmonary rheumatoid nodules; Leflunomide; Video-associated thoracoscopy; Histological findings
ID Intrapulmonary rheumatoid nodules; Leflunomide; Video-associated thoracoscopy; Histological findings
AB Rheumatoid nodules are well established manifestations of rheumatoid arthritis but in the lungs they are very rare according to the literature. In our study we present the case of a 34-year-old woman with rheumatoid arthritis and secondary Sjogren’s syndrome who developed multiplex rheumatoid nodules in the lungs 3 years after initiating leflunomide therapy. During leflunomide therapy we did not detect inflammation in the joints. Surprisingly, in November 2005 she started to cough, had low grade fever and low back pain. On the chest X-ray there were multiplex necrobiotic nodules in the lungs. All bacteriological, viral and fungal investigations including tuberculosis, serological tests and cytology were negative. The X-ray, video-associated thoracoscopy and repeated biopsy of the lung followed by histology of the samples proved intrapulmonary rheumatoid nodules, caused by leflunomide.
C1 [Horvath, Fanny Ildiko] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. str 22, 4004 Debrecen, Hungary.
[Szanto, Antonia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. str 22, 4004 Debrecen, Hungary.
[Csiki, Zoltan] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. str 22, 4004 Debrecen, Hungary.
[Szodoray, Peter] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. str 22, 4004 Debrecen, Hungary.
[Zeher, Margit] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. str 22, 4004 Debrecen, Hungary.
RP Zeher, M (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4004 Debrecen, Hungary.
EM zeher@iiibel.dote.hu
CR Scadding JG, 1969, The lungs in rheumatoid arthritis. Proc R Soc Med 62:227–238
Hull S, Mathews JA, 1982, Pulmonary necrobiotic nodules as a presenting feature of rheumatoid arthritis. Ann Rheum Dis 41: 21–24
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Laloux L, Chevalier X, Maitre B, Lange F, Chanzy MO, Larget- Piet B, Claudepierre P, 1999, Unusual onset of rheumatoid arthritis with diffuse pulmonary nodulosis: a diagnostic problem. J Rheumatol 26:920–922
Teruuchi S, Bando M, Suqiyama Y, Kitamura S, Murayama H, Sohara Y, Hironaka M, Kuriki K, Saito K, 1999, Multiple intrapulmonary rheumatoid nodules. Nihon Kokyuki Gakkai Zasshi 37:829–833
Karadaq F, Polatli M, Senturk T, Kacar F, Sen S, Clidaq O, 2003, Cavitary necrobiotic nodule imitating malignant lung disease in a patient without articular manifestations of rheumatoid arthritis. J Clin Rheumatol 9:246–252
Kitamura A, Matsuno T, Narita M, Shimokata K, Yamashita Y, Mori N, 2004, Rheumatoid arthritis with diffuse pulmonary rheumatoid nodules. Pathol Int 54:798–802
Kobayashi T, Satoh K, Ohkawa M, Satoh A, 2005, Multiple rheumatoid nodules with rapid thin-walled cavity formation producing pneumothorax. J Thorac Imaging 20:47–49
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Rozin A, Yigla M, Guralnik L, Keidar Z, Vlodavsky E, Rozenbaum M, Nahir AM, Balbir-Gurman A, 2006, Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. Clin Rheumatol 25:384–388
Braun MG, Van Rhee R, Becker-Capeller D, 2004, Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy. Z Rheumatol 63:84–87
Ulusoy H, Bilgici A, Kuru O, Celenk C, 2005, Pulmonary abscess due to leflunomide use in rheumatoid arthritis: a case report. Rheumatol Int 25:139–142
Kamata Y, Nara H, Kamimura T, Haneda K, Iwamoto M, Masuyama J, Okazaki H, Minota S, 2004, Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reaction. Intern Med 43:1201–1204
Takeishi M, Akiyama Y, Akiba H, Adachi D, Hirano M, Mimura T, 2005, Leflunomide induced acute interstitial pneumonia. J Rheumatol 32:1160–1163
Sakai F, Noma S, Kurihara Y, Yamada H, Azuma A, Kudoh S, Ichikawa Y, 2005, Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features. Mod Rheumatol 15:173–179
Suissa S, Hudson M, Ernst P, 2006, Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. Arthritis Rheum 54:1435–1439
Ochi S, Hariqai M, Mizoquchi F, Iwai H, Haqiyama H, Oka T, Miyasaka N, 2006, Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis: autopsy findings with a mosaic pattern of acute and organizing diffuse alveolar damage. Mod Rheumatol 16:316–320
Smith CA, Arnett FC, 1991, Diagnosing rheumatoid arthritis: current criteria. Am Fam Physician 44:863–870
Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjogren’s Syndrome, 2002, Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American–European Consensus Group. Ann Rheum Dis 61:554–558
Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, Fry- Smith A, Burls A, 2006, A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess 10:1–229
Ostor AJ, Chilvers ER, Somerville MF, Lim AY, Lane SE, Crisp AJ, Scott DG, 2006, Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. J Rheumatol 33:622–628
Hansen KE, Hildebrand JP, Genovese MC, Cush JJ, Patel S, Cooley DA, Cohen SB, Gangnon RE, Schiff M, 2004, The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis. Arthritis Rheum 51:228–232
Korkmaz C, Us T, Kasifoglu T, Akgun Y, 2006, Anti-cyclic citrullinated peptide, CCP, antibodies in patients with longstanding rheumatoid arthritis and their relationship with extraarticular manifestations. Clin Biochem 39:961–965
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2008
VL 14
IS 1
BP 101
EP 104
DI 10.1007/s12253-008-9003-6
PG 4
ER
PT J
AU Bianchi, S
Vezzosi, V
AF Bianchi, Simonetta
Vezzosi, Vania
TI Microinvasive Carcinoma of the Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Microinvasion; Definition; Diagnosis; Clinical significance; Breast cancer
ID Microinvasion; Definition; Diagnosis; Clinical significance; Breast cancer
AB The increased rate of early detection of breast cancer due to widespread mammographic screening has led to an increased incidence not only of in situ but also microinvasive carcinoma (MC). MC has been reported to have a favourable prognosis, but specific definitions have varied in the past making the clinical significance of this entity a subject of debate. In fact, although the diagnosis of MC often appears in pathology reports, this term has not been used in a consistent, standardized manner. In addition, the histological diagnosis of MC can be problematical for the pathologist due to a variety of in situ patterns and artefacts that may be misinterpreted as stromal invasion. Definitions and diagnostic criteria of MC are reviewed and discussed. Based on a review of literature, incidence of axillary lymph node involvement, according to different definitions of microinvasion, is reported.
C1 [Bianchi, Simonetta] AOU Careggi, Department of Human Pathology and Oncology, Viale Morgagni 85, 50134 Florence, Italy.
[Vezzosi, Vania] AOU Careggi, Department of Human Pathology and Oncology, Viale Morgagni 85, 50134 Florence, Italy.
RP Bianchi, S (reprint author), AOU Careggi, Department of Human Pathology and Oncology, 50134 Florence, Italy.
EM simonetta.bianchi@unifi.it
CR Georgian-Smith D, Lawton TJ, 2001, Calcifications of lobular carcinoma in situ of the breast: radiologic–pathologic correlation. AJR 176:1255–1258
Sapino A, Frigerio A, Peterse JL et al, 2000, Mammographically detected in situ lobular carcinoma of the breast. Virchows Arch 436:421–430
Hanby AM, Hughes TA, 2008, In situ and invasive lobular neoplasia of the breast. Histopathology 52:58–66
Tavassoli FA, 1999, Pathology of the breast, 2nd edn. Appleton & Lange, Stanford
Boecker W, Parker S, Schulz-Wendtland R et al, 2006, Ductal carcinoma in situ. In: Boecker W, ed, Preneoplasia of the breast. A new conceptual approach to proliferative breast disease. Elsevier GmbH, Munich
Nemoto T, Castillo N, Tsukada Y et al, 1998, Lobular carcinoma in situ with microinvasion. J Surg Oncol 67:41–46
Hoda SA, Chiu A, Prasad ML et al, 2000, Are microinvasion and micrometastasis in breast cancer mountains or molehills? Am J Surg 180:305–308
Lagios MD, Wesdahl PR, Margolin FR et al, 1982, Duct carcinoma in situ. Relationship of extent of non invasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures. Cancer 50:1309–1314
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Wong JH, Kopald KH, Morton DL, 1990, The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer. Arch Surg 125:1298–1301
Silverstein MJ, Waisman JR, Gamagami P et al, 1990, Intraductal carcinoma of the breast, 208 cases): clinical factors influencing treatment choice. Cancer 66:102–108
National Coordinating Group for Breast Cancer Screening Pathology, 1990, Pathology reporting in breast cancer screening. NHSBSP Publications, Sheffield
Sloane JP, 1991, Pathology reporting in breast cancer screening. J Clin Pathol 44:710–725
Rosner D, Lane WW, Penetrante R, 1991, Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy. Cancer 67:1498–1503
Solin LJ, Fowble BL, Yeh IT et al, 1992, Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation. Int J Radiat Oncol Biol Phys 23:961–968
Silver SA, Tavassoli FA, 1998, Mammary ductal carcinoma insitu with microinvasion. Cancer 82:2382–2390
De Mascarel I, MacGrogan G, Mathoulin-Pelissier S et al, 2002, Breast ductal carcinoma in situ with microinvasion. A definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 94:2134–2142
Sobin LH, Wittekind CH, eds,, 1997, Breast tumors in TNM classification of malignant tumors, 5th edn. Wiley-Liss, New York
National Coordinating Group for Breast Cancer Screening Pathology, 1995, Pathology reporting in breast cancer screening, 2nd edn. NHSBSP Publications, Sheffield
Tavassoli FA, Devilee P, eds,, 2003, World health organization classification of tumours. Pathology and genetics of the tumours of the breast and female genital organs. IARC, Lyon
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Schnitt SJ, 1998, Microinvasive carcinoma of the breast: a diagnosis in search of a definition. Adv Anat Pathol 5:367–372
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Padmore RF, Fowble B, Hoffman J et al, 2000, Microinvasive breast carcinoma: clinicopathologic analysis of a single institution experience. Cancer 88:1403–1409
Prasad ML, Osborne MP, Giri DD et al, 2000, Microinvasive carcinoma, T1 mic, of the breast: clinicopathologic profile of 21 cases. Am J Surg Pathol 24:422–428
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Wasserberg N, Morgenstern S, Schachter J et al, 2002, Risk factors for lymph node metastases in breast ductal carcinoma in situ with minimal invasive component. Ann Surg 137:1249–1252
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Yang M, Moriya T, Oguma M et al, 2003, Microinvasive ductal carcinoma, T1mic, of the breast. The clinicopathological profile and immunohistochemical features of 28 cases. Pathol Int 53:422–428
Buttarelli M, Houvenaeghel G, MartinoMet al, 2004, Prelevement de ganglions sentinelles dans les carcinomes intracanalaires du sein, ± microinvasion). Ann Chir 129:1105–1111
Giard S, Chauvet MP, Houpeau JL et al, 2005, Le ganglion sentinelle sans curage systematique dans le cancer du sein: bilan d’une experience de 1000 interventions. Gynelcol Obstet Fertil 33:213–219
Wilkie C, White L, Dupont D et al, 2005, An update of sentinel lymph node mapping in patients with ductal carcinoma in situ. Am J Surg 190:563–566
Katz A, Gage I, Evans S et al, 2006, Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer. Am J Surg 191:761–766
Leidenius M, Salmenkivi K, Von Smitten K et al, 2006, Tumourpositive sentinel node findings in patients with ductal carcinoma in situ. J Surg Oncol 94:380–384
Gray RJ, Mulheron B, Pockaj BA et al, 2007, The optimal management of the axillae of patients with microinvasive breast cancer in the sentinel lymph node era. Am J Surg 194:845–849
Le Bouedec G, de Lapasse C, Mishellany F et al, 2007, Microinvasive ductal carcinoma of the breast. Role of sentinel lymph node biopsy. Gynecol Obstet Fertil 35:317–322
Zavagno G, Belardinelli V, Marconato R et al, 2007, Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion. Breast 16:146–151
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 105
EP 111
DI 10.1007/s12253-008-9054-8
PG 7
ER
PT J
AU Lee, HSA
Ellis, OI
AF Lee, H S Andrew
Ellis, O Ian
TI The Nottingham Prognostic Index for Invasive Carcinoma of the Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Carcinoma of breast; Histological grade; Prognosis; Nottingham prognostic index
ID Carcinoma of breast; Histological grade; Prognosis; Nottingham prognostic index
AB A useful prognostic factor in breast cancer has key roles, including identification of a group of patients whose prognosis is so good they do not require further treatment, such as adjuvant systemic therapy, after local surgery, and secondly a group with a poor prognosis for whom additional treatment would be appropriate. To be of clinical use, prognostic factors must show a wide separation in the outcome of the groups identified and select adequate numbers in each group. No single prognostic factor in invasive carcinoma of the breast satisfies all these criteria. However, the Nottingham prognostic index (NPI), which combines nodal status, tumour size and histological grade, does satisfy these criteria. The NPI has been validated by further studies in Nottingham and by studies in several other countries. Predictive factors, such as oestrogen receptor and HER-2 status, predict whether a tumour is likely to respond to a treatment, and are complimentary to prognostic factors. The NPI can be used in combination with predictive factors to select patients for systemic adjuvant treatments. There is the potential to improve the NPI by inclusion of other factors, such as vascular invasion, but any such alterations would require further validation.
C1 [Lee, H S Andrew] Nottingham University Hospitals, Department of Histopathology, City Hospital Campus, NG5 1PB Nottingham, UK.
[Ellis, O Ian] Nottingham University Hospitals, Department of Histopathology, City Hospital Campus, NG5 1PB Nottingham, UK.
RP Lee, HSA (reprint author), Nottingham University Hospitals, Department of Histopathology, NG5 1PB Nottingham, UK.
EM andrew.lee@nuh.nhs.uk
CR Clark GM, Hilsenbeck SG, Ravdin PM, De Laurentis M, Osborne CK, 1994, Prognostic factors: rationale and methods of analysis and integration. Breast Cancer Res Treat 32:105–112
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 113
EP 115
DI 10.1007/s12253-008-9067-3
PG 3
ER
PT J
AU Cserni, G
AF Cserni, Gabor
TI Minimal Disease in Sentinel Nodes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast cancer; Sentinel lymph node; Micrometastasis; Isolated tumor cells
ID Breast cancer; Sentinel lymph node; Micrometastasis; Isolated tumor cells
AB Isolated tumor cells and micrometastases represent low-volume or minimal disease in the regional lymph nodes of breast cancer patients as compared to macrometastases. Sentinel lymph node biopsy is a functional selection and removal of the most likely site of regional metastasis, and gives pathologists the opportunity to concentrate detection techniques on a limited number of lymph nodes. Consequently, more lesions belonging in the two mentioned staging categories are discovered in sentinel lymph nodes. Despite some publications contradicting stochastic models of breast cancer, micrometastases seem to reflect a prognosis intermediate between the nodenegative and macrometastatic nodal status, and they also reflect a risk of non-sentinel node involvement slightly higher than that associated with a node-negative status. Data are more contradictory as concerns isolated tumor cells. This minireview summarizes the definitions, their inconsistencies, pathological protocols aiming at the detection of minimal nodal disease, the prognostic impact and non-sentinel node involvement related risk of such nodal lesions, and their therapeutic consequences.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Nyiri ut 38., H6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, H6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Saphir O, Amromin GD, 1948, Obscure axillary lymph node metastasis in carcinoma of the breast. Cancer 1:238–241
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Cserni G, Amendoeira I, Apostolikas N et al, 2004, Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology. J Clin Pathol 57:695–701
Cserni G, 2004, A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol 57:467– 471
Weigelt B, Verduijn P, Bosma AJ et al, 2004, Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple mRNA markers. Br J Cancer 90:1531–1537
Blumencranz P, Whitworth PW, Deck K et al, 2007, Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors. Am J Surg 194:426–432
Maiorano E, Mazzarol GM, Pruneri G et al, 2003, Ectopic breast tissue as a possible cause of false-positive axillary sentinel lymph node biopsies. Am J Surg Pathol 27:513–518
Orr RK, 1999, The impact of prophylactic axillary node dissection on breast cancer survival—a Bayesian meta-analysis. Ann Surg Oncol 6:109–116
Vinh-Hung V, Verschraegen C, 2004, Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 96:115–121
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Hellman S, 1994, Karnofsky Memorial Lecture. Natural history of small breast cancers. J Clin Oncol 12:2229–2234
Cserni G, 2007, What is a positive sentinel lymph node in a breast cancer patient? A practical approach. Breast 16:152–160
Degnim AC, Griffith KA, Sabel MS et al, 2003, Clinicopathologic features of metastasis in nonsentinel lymph nodes of breast carcinoma patients. Cancer 98:2307–2315
Van Zee KJ, Manasseh DM, Bevilacqua JL et al, 2003, A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 10:1140–1151
Hwang RF, Krishnamurthy S, Hunt KK et al, 2003, Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer. Ann Surg Oncol 10:248–254
Farshid G, Pradhan M, Kollias J et al, 2004, A decision aid for predicting non-sentinel node involvement in women with breast cancer and at least one positive sentinel node. Breast 13:494–501
Barranger E, Coutant C, Flahault A et al, 2005, An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement. Breast Cancer Res Treat 91:113–119
Degnim AC, Reynolds C, Pantvaidya G et al, 2005, Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg 190, 4):543–550 2005 Oct
Chagpar AB, Scoggins CR, Martin RC 2nd et al, 2006, Prediction of sentinel lymph node-only disease in women with invasive breast cancer. Am J Surg 192:882–887
Kocsis L, Svebis M, Boross G et al, 2004, Use and limitations of a nomogram predicting the likelihood of non-sentinel node involvement after a positive sentinel node biopsy in breast cancer patients. Am Surg 70:1019–1024
Cserni G, Bianchi S, Vezzosi V et al, 2007, Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients. Am J Surg 194:288–293
Cserni G, 2007, Comparison of different validation studies on the use of the Memorial-Sloan Kettering Cancer Center nomogram predicting nonsentinel node involvement in sentinel node-positive breast cancer patients. Am J Surg 194:699–700
Alran S, De Rycke Y, Fourchotte V et al, 2007, Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy. Ann Surg Oncol 14:2195–2201
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Leidenius MH, Vironen JH, Riihela MS et al, 2005, The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases. Eur J Surg Oncol 31:13–18
Houvenaeghel G, Nos C, Mignotte H et al, 2006, Micrometastases in sentinel lymph node in a multicentric study: predictive factors of nonsentinel lymph node involvement—Groupe des Chirurgiens de la Federation des Centres de Lutte Contre le Cancer. J Clin Oncol 24:1814–1822
Cserni G, Bianchi S, Boecker W et al, 2005, Improving the reproducibility of diagnosing micrometastases and isolated tumor cells. Cancer 103:358–367
Cserni G, Sapino A, Decker T, 2006, Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting. Breast 15:347–354
Lebeau A, Cserni G, Dietel M et al, 2007, Pathological examination of sentinel lymph nodes: work-up—interpretation— clinical implications. Breast Care 2:102–108
Turner RR, Weaver DL, Cserni G et al, 2008, Nodal stage classification for breast carcinoma: improving interobserver reproducibility through standardized histologic criteria and image- based training. J Clin Oncol 26:258–263
Querzoli P, Pedriali M, Rinaldi R et al, 2006, Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients. Clin Cancer Res 12:6696–6701
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 117
EP 121
DI 10.1007/s12253-008-9052-x
PG 5
ER
PT J
AU Egyed, Zs
Pentek, Z
Jaray, B
Kulka, J
Svastics, E
Kas, J
Laszlo, Zs
AF Egyed, Zsofia
Pentek, Zoltan
Jaray, Balazs
Kulka, Janina
Svastics, Egon
Kas, Jozsef
Laszlo, Zsolt
TI Radial Scar-Significant Diagnostic Challenge
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Mammography; Diagnostic error; Radial scar; Black star - white star; Triple test assessment
ID Breast cancer; Mammography; Diagnostic error; Radial scar; Black star - white star; Triple test assessment
AB The prevalence of radial scar (RS) is 0.04% in asymptomatic women participating in population screening for breast cancer. It is important to differentiate RS from concomitant malignancies, which occur in 20–30% of patients, or from small stellate carcinomas which give similar radiomorphology. The aim of our study was to evaluate the effectivity of current breast diagnostic methods in distinguishing between real RS, concomitant malignancy and carcinomas imitating RS. Diagnosis of RS was set up in 61 cases by mammography. Forty-four patients underwent surgical excision: histology showed benign or malignant lesions in 28 and 16 cases, respectively. A series of negative results at follow-up proved the benign nature of the lesion in further 11 cases. Six patients were not available for follow-up. Results of mammography, physical examination, ultrasonography and cytology were evaluated and were compared in 39 benign and 16 malignant cases. Results of examinations were reported on the BI-RADS scale ranging from 1 to 5. The mean categorical scores of all diagnostic processes were around the level of borderline lesions: mammography: 3.49, ultrasonography: 3.06, cytology: 2.47 and physical examination: 1.67. The average age of the patients in the benign and malignant groups were the same: 58 years. The two groups did not differ significantly over either distribution of coded mammographical results (p = 0.2092), or the distribution of mammographical parenchyma density patterns (p = 0.4875). However, the malignant and benign groups differed significantly from each other over the distribution of coded ultrasonographic (p = 0.0176) and cytological (p < 0.0001) results. In conclusion, in the preoperative diagnosis of asymptomatic "black-stars", mammography detects the non-palpable lesions, and ultrasonography together with cytology proved better in the analysis, provided FNAB is US guided. Due to the complex diagnostic approach the nature of the "black stars" is known in the majority of cases prior to the surgical biopsy.
C1 [Egyed, Zsofia] MaMMa Egeszsegugyi Rt, Kapas u. 29, H-1023 Budapest, Hungary.
[Pentek, Zoltan] MaMMa Egeszsegugyi Rt, Kapas u. 29, H-1023 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Svastics, Egon] Budai MAV Hospital, Department of SurgeryBudapest, Hungary.
[Kas, Jozsef] Budai MAV Hospital, Department of SurgeryBudapest, Hungary.
[Laszlo, Zsolt] MaMMa Egeszsegugyi Rt, Kapas u. 29, H-1023 Budapest, Hungary.
RP Egyed, Zs (reprint author), MaMMa Egeszsegugyi Rt, H-1023 Budapest, Hungary.
EM egyed.zsofia@axelero.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 123
EP 129
DI 10.1007/s12253-008-9025-0
PG 7
ER
PT J
AU Kipikasova, L
Wolaschka, T
Bohus, P
Baumohlova, H
Bober, J
Blazejova, J
Mirossay, L
Sarissky, M
Mirossay, A
Cizmarikova, M
Potocekova, D
Mojzis, J
AF Kipikasova, Livia
Wolaschka, Tomas
Bohus, Peter
Baumohlova, Helena
Bober, Juraj
Blazejova, Jana
Mirossay, Ladislav
Sarissky, Marek
Mirossay, Andrej
Cizmarikova, Martina
Potocekova, Dana
Mojzis, Jan
TI Polymorphisms of the XRCC1 and XPD Genes and Breast Cancer Risk: A Case-Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer susceptibility; DNA repair; XPD; XRCC1
ID Breast cancer susceptibility; DNA repair; XPD; XRCC1
AB The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction–restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P<0.0001, odds ratio=2.14; 95% confidence interval 1.44–3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility.
C1 [Kipikasova, Livia] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Wolaschka, Tomas] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Bohus, Peter] University Hospital, Department of PathologyKosice, Slovakia.
[Baumohlova, Helena] University Hospital, Department of PathologyKosice, Slovakia.
[Bober, Juraj] P.J. Safarik University, Faculty of Medicine, 1st Surgery DepartmentKosice, Slovakia.
[Blazejova, Jana] P.J. Safarik University, Faculty of Medicine, 1st Surgery DepartmentKosice, Slovakia.
[Mirossay, Ladislav] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Sarissky, Marek] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Mirossay, Andrej] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Cizmarikova, Martina] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
[Potocekova, Dana] P.J. Safarik University, Faculty of Medicine, Department of InformaticsKosice, Slovakia.
[Mojzis, Jan] P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
RP Mojzis, J (reprint author), P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, 040 11 Kosice, Slovakia.
EM jan.mojzis@upjs.sk
CR Parkin DM, Bray F, Ferlay J et al, 2005, Global cancer statistics. CA Cancer J Clin 55:74–108
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 131
EP 135
DI 10.1007/s12253-008-9034-z
PG 5
ER
PT J
AU Thielemann, A
Kopczynski, Z
Filas, V
Breborowicz, J
Grodecka-Gazdecka, S
Baszczuk, A
AF Thielemann, Anna
Kopczynski, Zygmunt
Filas, Violetta
Breborowicz, Jan
Grodecka-Gazdecka, Sylwia
Baszczuk, Aleksandra
TI The Determination of VEGF and MVD, among Patients with Primary Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiogenesis; Breast cancer; Microvessel density; Neoplasm; Vascular endothelial growth factor
ID Angiogenesis; Breast cancer; Microvessel density; Neoplasm; Vascular endothelial growth factor
AB The purpose of the study was to ascertain the value of assessment of vascular endothelial growth factor (VEGF) levels and microvessel density, and to search for correlations between them, in women with breast cancer. The assessment considered factors such as the stage of clinical disease advancement—according to International Union Against Cancer, the grade of histological malignancy, status of axillary lymph nodes and the size of the primary tumour. The concentration of VEGF was assessed in the plasma of 103 women with breast cancer, using an immunoenzymatic method (Quantikine test of R&D Systems). Assessment of microvessel density was performed using histopathological immunoperoxidase methods, using an anti-von Willebrand factor antibody (DAKO A/S). A statistically significant relationship was found between rising VEGF levels and microvessel density in women with breast cancer, when compared to values from a control group. A correlation was found between VEGF concentration and microvessel density (MVD) values. Statistically significant differences were found between VEGF levels of patients in stages I, II and III of clinical disease advancement. For MVD, differences were found only between stages I and III. A statistical relationship was also found between VEGF and MVD and tumour size. Similar results were found between VEGF concentrations in women with metastases to the axillary lymph nodes and cytokine levels in women with no metastases. The results of the study suggest that the degree of tumour vascularization and the concentration of VEGF may represent valuable indicators for the assessment of the angiogenic process in women with breast cancer.
C1 [Thielemann, Anna] Poznan University of Medical Sciences, Department of Laboratory Medicine, Lakowa St. No 1/2, 61-878 Poznan, Poland.
[Kopczynski, Zygmunt] Poznan University of Medical Sciences, Department of Laboratory Medicine, Lakowa St. No 1/2, 61-878 Poznan, Poland.
[Filas, Violetta] Poznan University of Medical Sciences, Department of Oncology, Department of Tumour PathologyPoznan, Poland.
[Breborowicz, Jan] Poznan University of Medical Sciences, Department of Oncology, Department of Tumour PathologyPoznan, Poland.
[Grodecka-Gazdecka, Sylwia] Poznan University of Medical Sciences, Department of Oncology, Department of Oncological SurgeryPoznan, Poland.
[Baszczuk, Aleksandra] Poznan University of Medical Sciences, Department of Laboratory Medicine, Lakowa St. No 1/2, 61-878 Poznan, Poland.
RP Thielemann, A (reprint author), Poznan University of Medical Sciences, Department of Laboratory Medicine, 61-878 Poznan, Poland.
EM anna.thielemann@oncology.am.poznan.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 137
EP 144
DI 10.1007/s12253-008-9040-1
PG 8
ER
PT J
AU Yuan, K
Listinsky, MC
Singh, KR
Listinsky, JJ
Siegal, PG
AF Yuan, Kun
Listinsky, M Catherine
Singh, K Raj
Listinsky, J Jay
Siegal, P Gene
TI Cell Surface Associated Alpha-L-Fucose Moieties Modulate Human Breast Cancer Neoplastic Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Fucose; Glycosylation; Matrix metalloproteases; Neoplastic progression
ID Breast cancer; Fucose; Glycosylation; Matrix metalloproteases; Neoplastic progression
AB Glycosylation drives critical processes important for mammalian cell–cell and cell–matrix interactions. Alpha-L-fucose (α-L-f) is a key monosaccharide component of oligosaccharides that has been found to be overexpressed during tumor progression. Modification of cell surface fucosylation, we hypothesized, alters tumor cell phenotype and function at the end of the neoplastic progression cascade including tumor invasion. Alpha-L-fucosidase (α-L-fase) is a glycosidase that specifically removes (α-L-f) from oligosaccharide sites. We first verified the effectiveness of the α-L-fase to specifically decrease the level of α-L-f on the cell surface of several human breast cancer cell lines and also examined the recovery time for these cells to repopulate their surfaces. To investigate the potential effect of defucosylation on tumor functions, we studied the proliferation, and invasion in vitro of human breast cancer MDA-MB-231 cells as the representative cell model. We further examined several fucose-associated molecules previously shown to be involved in tumor progression, including CD44 and CD15 (Lewis X antigen). We found that α-L-fase pretreatment significantly decreased the invasive capability of breast cancer cells. Deoxyfuconojirimycin (DFJ), a specific α-L-fase inhibitor, reversed this effect. After fucosidase treatment, the level of both CD15 and CD44 were found to be reduced as measured by flow cytometry. α-L-fase treatment, further, did not affect tumor cell proliferation in vitro under identical experimental conditions. Gelatin zymography of conditioned media from tumor cells treated with α-L-fase demonstrated no change in MMP-2 activity while MMP-9 was significantly reduced. In summary, fucose containing glycans were found widely distributed on the cell surface of breast cancer cells and could be effectively removed by α-L-fase treatment. This decreased fucosylation, in turn, was seen to impair the interaction between tumor cells and extracellular matrices, and thus affected key cell functions modulating tumor invasion. Further elucidation of the molecular pathways involved in the inhibition of tumor cell invasion may suggest a rationale for the use of glycobiologic therapeutics to deter tumor progression.
C1 [Yuan, Kun] University of Alabama at Birmingham, Department of Pathology, 35233 Birmingham, AL, USA.
[Listinsky, M Catherine] University of Alabama at Birmingham, Department of Pathology, 35233 Birmingham, AL, USA.
[Singh, K Raj] University of Alabama at Birmingham, Department of Pathology, 35233 Birmingham, AL, USA.
[Listinsky, J Jay] University of Alabama at Birmingham, Department of Diagnostic Radiology, 35233 Birmingham, AL, USA.
[Siegal, P Gene] University of Alabama at Birmingham, Department of Pathology, 35233 Birmingham, AL, USA.
RP Siegal, PG (reprint author), University of Alabama at Birmingham, Department of Pathology, 35233 Birmingham, USA.
EM gsiegal@uab.edu
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Liu F Zhang Y, Zhang XY, et al, 2002, Transfection of the nm23- H1 gene into human hepatocarcinoma cell line inhibits the expression of sialyl Lewis X, alpha1,3 fucosyltransferase VII, and metastatic potential. J Cancer Res Clin Oncol 128(4):189–196
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 145
EP 156
DI 10.1007/s12253-008-9036-x
PG 12
ER
PT J
AU Abdul, M
Ramlal, S
Hoosein, N
AF Abdul, Mansoor
Ramlal, Sian
Hoosein, Naseema
TI Ryanodine Receptor Expression Correlates with Tumor Grade in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ryanodine receptor; Breast cancer; Tumor grade; 4-chloro-m-cresol; MCF-7; MDA-MB-231
ID Ryanodine receptor; Breast cancer; Tumor grade; 4-chloro-m-cresol; MCF-7; MDA-MB-231
AB Ryanodine receptors (RyRs) have been previously implicated in the proliferation of human T-lymphocytes and melanocytes as well as in the motility of astrocytes. We have examined RyR expression in 57 ductal, human breast cancer specimens, by immunohistochemistry. Moderate to high RyR immunostaining was found in 47 (82%) of the specimens. There was a direct correlation between RyR levels and tumor grade (r=0.48, p=0.0002). We have also examined the effect of the RyR agonist 4-chloro-m-cresol on the in-vitro growth of two human breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with 4-chlorom-cresol inhibited the growth of both breast cancer cell lines, in a dose-dependent manner, with half-maximal inhibition observed at 30 to 50 μg/mL (210–351 μM). Our data suggest that RyR could serve as prognostic indicator and/or as a target for breast cancer treatment.
C1 [Abdul, Mansoor] Claflin University, Biology Department, 400 Magnolia Street, 29115 Orangeburg, SC, USA.
[Ramlal, Sian] Claflin University, Biology Department, 400 Magnolia Street, 29115 Orangeburg, SC, USA.
[Hoosein, Naseema] Claflin University, Biology Department, 400 Magnolia Street, 29115 Orangeburg, SC, USA.
RP Hoosein, N (reprint author), Claflin University, Biology Department, 29115 Orangeburg, USA.
EM nhoosein@claflin.edu
CR Bootman MD, Lipp P, Berridge MJ, 2001, The organization and functions of local Ca(2+, signals. J Cell Sci 114:2213–2222
Mackrill JJ, 1999, Protein–protein interactions in intracellular Ca2+-release channel function. Biochem J 337:345–361
Fill M, Copello JA, 2002, Ryanodine receptor calcium release channels. Physiol Rev 82:893–922
Hakamata Y, Nishimura S, Nakai J et al, 1994, Involvement of the brain type of ryanodine receptor in T-cell proliferation. FEBS Lett 352:206–210
Kang HY, Kim NS, Lee CO et al, 2000, Expression and function of ryanodine receptors in human melanocytes. J Cell Physiol 185:200–206
Matyash M, Matyash V, Nolte C et al, 2002, Requirement of functional ryanodine receptor type 3 for astrocyte migration. FASEB J 16:84–86
Mariot P, Prevarskaya N, Roudbaraki M et al, 2000, Evidence of functional ryanodine receptor involved in apoptosis of prostate cancer, LNCaP, cells. Prostate 43:205–214
Timar J, Kasler M, Katai J et al, 2006, Developments in cancer management by innovative genomics: 2006 report of the National Cancer Consortium. Hungarian Oncology 50:349–359
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 157
EP 160
DI 10.1007/s12253-008-9045-9
PG 4
ER
PT J
AU Palka, I
Kelemen, Gy
Ormandi, K
Lazar, Gy
Nyari, T
Thurzo, L
Kahan, Zs
AF Palka, Istvan
Kelemen, Gyongyi
Ormandi, Katalin
Lazar, Gyorgy
Nyari, Tibor
Thurzo, Laszlo
Kahan, Zsuzsanna
TI Tumor Characteristics in Screen-Detected and Symptomatic Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adjuvant therapy; Casting calcifications; Mammographic screening; Mammographic image; Prognosis
ID Adjuvant therapy; Casting calcifications; Mammographic screening; Mammographic image; Prognosis
AB The natural course of early breast cancer has changed as a result of the introduction of mammographic screening. The present aim was a prospective analysis of screen-detected and symptomatic operable breast cancers in the era of mammographic service screening. The mode of detection (screen-detected, symptomatic or interval cancer), the type of mammographic image and other characteristics (the invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status and the presence of lymphovascular invasion) of 569 invasive breast cancers were studied. Screen-detected cancers were significantly more frequently of grade I, <10 mm of size and nodenegative (p<0.001, respectively). Symptomatic/interval cancers were significantly more frequently of grade 3, >20 mm of size (p<0.001), and exhibited lymphovascular invasion (p=0.001). Screening-detection of the tumor favored breast-conserving surgery, sentinel lymph node biopsy and the avoidance of chemotherapy (p<0.001). Cancers associated with casting-type calcifications on the mammogram were typically of ductal type (p=0.043), of grade 2–3, estrogen receptor and progesterone receptornegative and HER2-positive (p<0.001). Interval cancers occurred significantly more often at a younger age and remained mammographically occult as compared with other cancers. Mammographic screen-detected cancers demonstrate more favorable prognostic features, and need less extensive treatment than symptomatic or interval cancers. The mammographic appearance of the tumor reflects its biological behavior, and this should be considered in the management optimization.
C1 [Palka, Istvan] University of Szeged, Department of PathologySzeged, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Ormandi, Katalin] University of Szeged, Department of RadiologySzeged, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
[Nyari, Tibor] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM kahan@onko.szote.u-szeged.hu
CR Tabar L, Fagerberg G, Duffy SW et al., 1989, The Swedish twocounty trial of mammographic screening for breast cancer: recent results and calculation of benefit. J Epidemiol Community Health 43:107–114
Tabar L, Yeng M-F, Vitak B et al., 2003, Mammography service screening and mortality in breast cancer patients: 20-year followup before and after introduction of screening. Lancet 361:1405– 1410
The Swedish Organised Service Screening Evaluation Group, 2006, Reduction of breast cancer mortality from organised service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev 15:45–51
Miller AB, Baines C, To T et al., 1992, Canadian national breast screening study. 1. Breast cancer detection and death rates among women aged 40 to 49 years. CMAJ 147:1459–1476
Kerlikowske K, Grady D, Rubin SM et al., 1995, Efficacy of screening mammography. A meta-analysis. JAMA 273:149–154
Cronin KA, Feuer EJ, Clarke LD, et al., 2006, Impact of adjuvant therapy and mammography on U.S. mortality from 1975 to 2000. Comparison of mortality results from the CISNET breast cancer base case analysis. J Natl Cancer Inst 36:112–121
Moody-Ayers SY, Wells CK, Feinstein AR, 2000, ”Benign” tumors and ”early detection” in mammography-screened patients of a natural cohort with breast cancer. Arch Intern Med 160:1109– 1115
Klemi PJ, Joensuu H, Tikkanen S et al., 1992, Aggressiveness of breast cancers found with and without screening. Br Med J 304:467–469
Klemi PJ, Parvinen I, Pylkkanen L et al., 2003, Significant improvement in breast cancer survival through population-based mammography screening. Breast 12:308–313
Anttinen J, Kautiainen H, Kuopo T, 2006, Role of mammography screening as a predictor of survival in postmenopausal breast cancer patients. Br J Cancer 94:147–151
Joensuu H, Lehtimaki T, Holli K et al., 2004, Risk for distant recurrence of breast cancer detected by mammography screening or other methods. JAMA 292:1064–1073
Shen Y, Yang Y, Inoues LYT et al., 2005, Role of detection method in predicting breast cancer survival: Analysis of randomized screening trials. J Natl Cancer Inst 97:1195–1203
Gill PG, Farshid G, Luke CG et al., 2005, Detection by screening mammography is a powerful independent predictor of survival in women diagnosed with breast cancer. Breast 13:15–22
ErnstMF, Voogd AC, Goebergh JWWet al., 2004, Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening. Cancer 100:1337–1344
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Thurfjell E, Thurfjell MG, Lindgren A, 2001, Mammographic finding as predictor of survival in 1–9 mm invasive breast cancers. Worse prognosis for cases presenting as calcifications alone. Breast Cancer Res Treat 67:177–180
Alexander MC, Yankaskas BC, Biesemier KW, 2006, Association of stellate mammographic pattern with survival in small invasive breast tumors. Am J Roentgenol 187:29–73
Peacock C, Given-Wilson RM, Duffy SW, 2004, Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator? Clin Radiol 59:165–170
Palka I, Ormandi K, Gaal S et al., in press, Casting-type calcifications on the mammogram indicate a higher probability of early relapse and death among operable high-risk breast cancer patients. Acta Oncol
Perry NM, 2001, Quality assurance in the diagnosis of breast disease. EUSOMA Working Party. Eur J Cancer 37:159–172
Ravdin PM, Siminoff LA, Davis GJ et al., 2001, Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19:980–991
Olivotto IA, Bajdik CD, Ravdin PM, et al., 2005, Populationbased validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 23:2716–2725
Porter PJ, El-Bastawissi AZ, Mandelson MT et al., 1999, Breast tumor characteristics as predictors of mammographic detection: Comparison of interval- and screen-detected cancers. J Natl Cancer Inst 91:2020–2028
Gilliland FD, Joste N, Stauber PM et al., 2000, Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 92:743–749
Crosier M, Scott D, Wilson RG et al., 1999, Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers. Clin Cancer Res 5:2682–2688
Porter GJ, Evans AJ, Cornford EJ et al., 2007, Influence of mammographic parenchymal pattern in screen-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival. Am J Roentgenol 188:676– 683
Porter GJ, Evans AJ, Burrell HC et al., 2007, NHSBSP type 1 interval cancers: a scientifically valid grouping? Clin Radiol 62:262–267
Zunzunegui RG, Chung MA, Oruwari J et al., 2003, Casting-type calcifications with invasion and high-grade ductal carcinoma in situ. Arch Surg 138:537–540
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 161
EP 167
DI 10.1007/s12253-008-9010-7
PG 7
ER
PT J
AU Pusztai, L
AF Pusztai, Lajos
TI Preoperative Systemic Chemotherapy and Pathologic Assessment of Response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Preoperative systemic therapy; Breast cancer
ID Preoperative systemic therapy; Breast cancer
AB Preoperative systemic (neoadjuvant) chemotherapy is both routine therapeutic modality for locally advanced breast cancer and a translational research model to identify biomarkers that predict treatment response. It is imperative that pathologic response be strongly prognostic in order to optimize the clinical and scientific information that can be gained from neoadjuvant clinical trials. Dichotomization of response as pathologic complete response (pCR) or residual disease (RD) is overly simplistic for these objectives, particularly because residual disease (RD) after neoadjuvant treatment includes a broad range of actual responses from near-pCR to frank resistance. More effective or prolonged neoadjuvant treatments should reduce the extent of RD in many patients, possibly blurring the prognostic distinction between pCR and RD. On the other hand, it should be possible to identify patients with resistant disease in order to develop predictive tests for this adverse outcome. Our research group recently proposed to measure residual cancer burden (RCB) as a continuous variable derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. Each component contributes meaningful pathologic information and can be obtained using routine pathologic materials and methods of interpretation that could easily be implemented in routine diagnostic practice.
C1 [Pusztai, Lajos] The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 77230-1439 Houston, TX, USA.
RP Pusztai, L (reprint author), The University of Texas, M. D. Anderson Cancer Center, Department of Breast Medical Oncology, 77230-1439 Houston, USA.
EM lpusztai@mdanderson.org
CR Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N, 2008, Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol 26:778–785
Boughey JC, Peintinger F, Meric-Bernstam F, Perry AC, Hunt KK, Babiera GV, Singletary SE, Bedrosian I, Lucci A, Buzdar AU, Pusztai L, Kuerer HM, 2006, Impact of preoperative versus postoperative chemotherapy on the extent and number of surgical procedures in patients treated in randomized clinical trials for breast cancer. Ann Surg 244:464–470
Bonadonna G, Veronesi U, Brambilla C et al, 1990, Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 82:1539–1545
Mauri D, Pavlidis N, Ioannidis JP, 2005, Neoadjuvant versus adjuvant systemic treatment in breast cancer: A meta-analysis. J Natl Cancer Inst 97:188–194
Chen AM, Meric-Bernstam F, Hunt KK et al, 2004, Breastconserving therapy after neoadjuvant chemotherapy: The M. D. Anderson Cancer Center experience. J Clin Oncol 22:2303–2312
Fisher B, Bryant J, Wolmark N et al, 1998, Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685
Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK et al, 2002, Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20:1456–1466
von Minckwitz G, Kummel S, Vogel P et al, 2008, Neoadjuvant vinorelbine–capecitabine versus docetaxel–doxorubicin–cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Je G, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski JA, 2008, Research issues affecting preoperative systemic therapy for operable breast cancer. J Clin Oncol 26:806–813
Carey LA, Metzger R, Dees EC et al, 2005, American Joint Committee on Cancer tumor–node–metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 97:1137–1142
Kuerer HM, Newman LA, Smith TL et al, 1999, Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469
Rouzier R, Extra JM, Klijanienko J et al, 2002, Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol 20:1304–1310
Mazouni C, Peintinger F, Kau SW, Andre F, Gonzalez-Angulo AM, Symmans WF, Meric-Bernstam F, Valero V, Hortobagyi GN, Pusztai L, 2007, Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol 25:2650–2655
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer HM, Valero V, Assad L, Poniecka A, Hennessy TJ, Green MC, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L, 2007, Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414–4422
Esteva FJ, Hortobagyi GN, 2008, Can early response assessment guide neoadjuvant chemotherapy in early-stage breast cancer? J Natl Cancer Inst 100:521–523
Rouzier R, Pusztai L, Delaloge S, Gonzalez-Angulo AM, Andre F, Hess KR, Buzdar AU, Garbay JR, Spielmann M, Mathieu MC, Symmans WF, Wagner P, Atallah D, Valero V, Berry DA, Hortobagyi GN, 2005, Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23:8331–8339
Andre F, Mazouni C, Liedtke C, Kau SW, Frye D, Green M, Gonzalez-Angulo AM, Symmans WF, Hortobagyi GN, Pusztai L, 2008, HER2 expression and efficacy of preoperative paclitaxel/ FAC chemotherapy in breast cancer. Breast Cancer Res Treat 108:183–190
Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J, Mariani G, Rodriguez J, Carcangiu M, Watson D, Valagussa P, Rouzier R, Symmans WF, Ross JS, Hortobagyi GN, Pusztai L, Shak S, 2005, Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265–7277
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 169
EP 171
DI 10.1007/s12253-008-9070-8
PG 3
ER
PT J
AU Tot, T
Gere, M
AF Tot, Tibor
Gere, Maria
TI Radiological–Pathological Correlation in Diagnosing Breast Carcinoma: The Role of Pathology in the Multimodality Era
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast; Breast cancer; Sick lobe hypothesis; Pathology; Radiological–pathological correlation; Large section technique
ID Breast; Breast cancer; Sick lobe hypothesis; Pathology; Radiological–pathological correlation; Large section technique
AB Breast carcinoma is a lobar disease, as the simultaneously or asynchronously appearing often multiple tumor foci originate from a single sick breast lobe. In its initial phase, the spatial pattern of malignant transformation may be lobar (targeting the entire lobe), segmental (targeting a segment) or terminal (targeting distant terminal ductal-lobular units) within the sick lobe. All these variations are properly characterized by the following parameters: the extent of the disease (the volume of the tissue containing all the actually present malignant structures within the breast), the distribution of the lesions within this tissue (unifocal, multifocal or diffuse, separately for in situ and invasive component), the size of the tumor (corresponding to the largest diameter of the largest invasive focus) and the exact localization of the lesion(s). In addition, intra- and intertumoral heterogeneity have to be noticed, if evident. Combining the results of different imaging modalities (mammography, ultrasound, magnetic resonance imaging) the radiologist may compensate the limitations of individual methods. This multimodality approach leads to more accurate radiological size measurement, more accurate assessment of the distribution of the lesions and disease extent. This represents a challenge for pathologists as the traditional histopathology method based on fragmentation and sampling of macroscopically suspicious lesion(s) is clearly insufficient for modern postoperative radiological–pathological correlation. There is a clear need for more complete examination of the excised tissue and for a three-dimensional reconstruction of the finding, preferably using continuous large tissue slices and two and three-dimensional large-format histological sections. Discordant results may still appear as a consequence of failure in radiological–pathological correlation or related to certain tumor subtypes as invasive lobular carcinoma of diffuse type, low grade in situ lesions or micropapillary ductal in situ carcinoma.
C1 [Tot, Tibor] Central Hospital, Department of Pathology and Clinical CytologyFalun, Sweden.
[Gere, Maria] Central Hospital, Department of Pathology and Clinical CytologyFalun, Sweden.
RP Tot, T (reprint author), Central Hospital, Department of Pathology and Clinical Cytology, Falun, Sweden.
EM tibor.tot@ltdalarna.se
CR Tot T, 2005, DCIS, cytokeratins and the theory of the sick lobe. Virchows Arch 447:1–8
Tot T, 2007, The theory of the sick lobe and the possible consequences. Int J Surg Pathol 15(4):369–375
Tot T, 2007, The clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histological sections. Cancer 110:2551–2560
Going JJ, Mohun TJ, 2006, Human breast duct anatomy, the ‘sick lobe’ hypothesis and intraductal approaches to breast cancer. Breast Cancer Res Treat 97:285–291
Foschini MP, Flaminio F, Miglio R et al, 2007, The impact of large sections on the study of in situ and invasive duct carcinoma of the breast. Hum Pathol 38:1736–1743
Tot T, Tabar L, Dean PB, 2002, Practical breast pathology. Thieme, Stuttgart—New York
Tabar L, Tot T, Dean PB, 2005, Breast cancer: the art and science of early detection with mammography: perception, interpretation, histopathologic correlation. Thieme, Stuttgart—New York
Tot T, Tabar L, 2006, Radiologic–pathologic correlation of ductal carcinoma in situ of the breast using two- and three-dimensional large histologic sections. Semin Breast Dis 8:144–151
Holland R, Hendricks JH, Vebeek AL et al, 1990, Extent, distribution, and mammographic/histological correlation of breast ductal carcinoma in situ. Lancet 335:519–522
Faverly DRG, Hendricks JHCL, Holland R, 2001, Breast carcinoma of limited extent. Frequency, radiologic–pathologic characteristics, and surgical margin requirements. Cancer 91:647– 659
Van Goethem M, Schelfout K, Dijkmans L et al, 2004, MR mammography in the pre-operative staging of breast cancer in patients with dense breast tissue: comparison with mammography and ultrasound. Eur Radiol 14:809–816
Berg WA, Gutierrez L, NessAiver MS et al, 2004, Diagnostic accuracy of mammography, clinical examination, US, and MRI imaging in preoperative assessment of breast cancer. Radiology 233:830–849
Tabar L, Tot T, Dean PB, 2007, Breast cancer: early detection with mammography. casting type calcifications: sign of a subtype with deceptive features. Thieme, Stuttgart-New York
Bosch AM, Kessels AG, Beets GL et al, 2003, Preoperative estimation of the pathological breast tumor size by physical examination, mammography and ultrasound: a prospective study of 105 invasive tumors. Eur J Radiol 48:285–292
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 173
EP 178
DI 10.1007/s12253-008-9061-9
PG 6
ER
PT J
AU Polgar, Cs
Kahan, Zs
Orosz, Zs
Gabor, G
Hadijev, J
Cserni, G
Kulka, J
Jani, N
Sulyok, Z
Lazar, Gy
Boross, G
Diczhazi, Cs
Szabo,
Laszlo, Zs
Pentek, Z
Major, T
Fodor, J
AF Polgar, Csaba
Kahan, Zsuzsanna
Orosz, Zsolt
Gabor, Gabriella
Hadijev, Janaki
Cserni, Gabor
Kulka, Janina
Jani, Nora
Sulyok, Zoltan
Lazar, Gyorgy
Boross, Gabor
Diczhazi, Csaba
Szabo, Eva
Laszlo, Zsolt
Pentek, Zoltan
Major, Tibor
Fodor, Janos
TI The Role of Radiotherapy in the Conservative Treatment of Ductal Carcinoma in Situ of the Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast-conserving therapy; Ductal carcinoma in situ; Endocrine therapy; Prognostic factors; Radiotherapy
ID Breast-conserving therapy; Ductal carcinoma in situ; Endocrine therapy; Prognostic factors; Radiotherapy
AB Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard of care for the treatment of early-stage (St. I-II) invasive breast carcinoma. However, controversy exists regarding the value of RT in the conservative treatment of ductal carcinoma in situ (DCIS). In this article we review the role of RT in the management of DCIS. Retrospective and prospective trials and meta-analyses published between 1975 and 2007 in the MEDLINE database, and recent issues of relevant journals/handbooks relating to DCIS, BCS and RT were searchedfor. In retrospective series (10,194 patients) the 10-year rate of local recurrence (LR) with and without RT was reported in the range of 9–28% and 22–54%, respectively. In four large randomised controlled trials (NSABP-B-17, EORTC-10853, UKCCCR, SweDCIS; 4,568 patients) 50 Gy wholebreast RT significantly decreased the 5-year LR rate from 16–22% (annual LR rate: 2.6–5.0%) to 7–10% (annual LR rate: 1.3–1.9%). In a recent meta-analysis of randomised trials the addition of RT to BCS resulted in a 60% risk reduction of both invasive and in situ recurrences. In a multicentre retrospective study, an additional dose of 10 Gy to the tumour bed yielded a further 55% risk reduction compared to RT without boost. To date, no subgroups have been reliably identified that do not benefit from RT after BCS. In the NSABP-B-24 trial, the addition of tamoxifen (TAM) to RT reduced ipsilateral (11.1% vs. 7.7%) and contralateral (4.9% vs. 2.3%) breast events significantly. In contrast, in the UKCCCR study, TAM produced no significant reduction in all breast events. Based on available evidence obtained from retrospective and prospective trials, all patients with DCIS have potential benefit from RT after BCS. Further prospective studies are warranted to identify subgroups of low-risk patients with DCIS for whom RT can be safely omitted. Until long-term results of ongoing studies on outcomes of patients treated with BCS alone (with or without TAM or aromatase inhibitors) are available, RT should be routinely recommended after BCS for all patients except those with contraindication.
C1 [Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Gabor, Gabriella] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Hadijev, Janaki] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of PathologyKecskemet, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Jani, Nora] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Sulyok, Zoltan] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
[Boross, Gabor] Bacs-Kiskun County Hospital, Department of SurgeryKecskemet, Hungary.
[Diczhazi, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Szabo, Eva] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Laszlo, Zsolt] MaMMa Egeszsegugyi RtBudapest, Hungary.
[Pentek, Zoltan] MaMMa Egeszsegugyi RtBudapest, Hungary.
[Major, Tibor] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Fodor, Janos] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
RP Polgar, Cs (reprint author), National Institute of Oncology, Center of Radiotherapy, 1122 Budapest, Hungary.
EM polgar@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 179
EP 192
DI 10.1007/s12253-008-9044-x
PG 14
ER
PT J
AU Kovacs,
Hadjiev, J
Lakosi, F
Glavak, Cs
Antal, G
Bogner, P
Horvath,
Repa, I
AF Kovacs, Arpad
Hadjiev, Janaki
Lakosi, Ferenc
Glavak, Csaba
Antal, Gergely
Bogner, Peter
Horvath, Akos
Repa, Imre
TI Comparison of Photon with Electron Boost in Treatment of Early Stage Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Boost; Breast cancer; Radiotherapy; Photon; Electron
ID Boost; Breast cancer; Radiotherapy; Photon; Electron
AB In the treatment of early stage breast cancer breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is a standard method. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study the electron and the photon boost techniques were compared. For 78 early stage breast cancer patients both CT based 3D conformal photon boost and electron boost plans were created. For dosimetric comparison coverage index (CI), external volume index (EI) and conformality index (COIN) were studied. Lung volume receiving a dose of 2 Gy was also reviewed. Seventy-eight patients with 156 plans were compared. The mean tumor bed volume was measured as 61.39 cm3 the mean tumor bed-skin distance was 3.13 cm. In the case of CI and COIN significant differences were found in favor of the photon boost. In the comparison of EI no significant difference was detected between the two techniques. The mean lung volume receiving 2 Gy were 42.3 and 168.35 cm3, for photons and electrons respectively. In the adjuvant treatment of early stage breast cancer WBI followed by conformal photon boost showed to be superior to electron boost in focus of the COIN and CI.
C1 [Kovacs, Arpad] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Hadjiev, Janaki] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Lakosi, Ferenc] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Glavak, Csaba] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Antal, Gergely] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Bogner, Peter] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Horvath, Akos] University of Debrecen, Medical and Health Science Center, Institute of Nuclear Medicine, Nagyerdei Krt. 98Debrecen, Hungary.
[Repa, Imre] Kaposi Mor Teaching HospitalKaposvar, Hungary.
RP Horvath, (reprint author), University of Debrecen, Medical and Health Science Center, Institute of Nuclear Medicine, Debrecen, Hungary.
EM horvakos@freemail.hu
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Ringash J, Whelan T, Elliott E et al, 2004, Accuracy of ultrasound in localization of breast boost field. Radiother Oncol 72:61–66
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American Joint Committee on Cancer, 2002, AJCC cancer staging handbook, sixth edition. Springer, Heidelberg, pp 263–267
International Commission on Radiation Units and Measurement, ICRU,, 1993, ICRU Report No. 50. Prescribing, recording and reporting photon beam therapy. ICRU, Washington, DC
Major T, Polgar CS, Fodor J, Somogyi A, Nemeth GY, 2002, Conformality and homogeneity of dose distributions in interstitial implants at idealized target volumes: a comparison between the Paris and dose-point optimized systems. Radiother Oncol 62:103–111
Polgar CS, Fodor J, Major T, Orosz ZS, Nemeth GY, 2001, The role of boost irradiation in the conservative treatment of stage I–II breast cancer. Pathol Oncol Res 7:241–250
Van Limbergen E, 2001, What are the optimal boost methods in relation to boost target depth in the breast? Proceedings of the Consensus Meeting on Breast Cancer: to boost or not to boost and how to do it. GEC-ESTRO, pp. 105–114.
Polgar CS, Sulyok Z, Major T et al, 2000, Reexcision and perioperative brachytherapy in the treatment of local relapse after breast conservation: a possible alternative to salvage mastectomy. Hungarian Surgery 53:120–123, in Hungarian)
Machtay M, Lanciano R, Hoffman J, Hanks GE, 1994, Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma. Int J Radiat Oncol Biol Phys 30:43–48
Baltas D, Kolotas C, Geramani K et al, 1998, A conformal index, COIN, to evaluate implant quality and dose specification in brachytherapy. Int J Radiat Oncol Biol Phys 40:515–524
Knoos T, Kristensen I, Nilsson P, 1998, Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index. Int J Radiat Oncol Biol Phys 42:1169–1176
RegineWF, Ayyangar KM, Komarnicky LT, Bhandare N, Mansfield CM, 1991, Computer-CT planning of the electron boost in definitive breast irradiation. Int J Radiat Oncol Biol Phys 20: 121–125
Smitt MC, Birdwell RL, Goffinet DR, 2001, Breast electron boost planning: comparison of CT and US. Radiology 219:203–206
Hunter MA, McFall TA, Hehr KA, 1996, Breast conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning. Radiology 200:281–282
Kovner F, Agay R, Merimsky O, Stadler J, Klausner J, Inbar M, 1999, Clips and scar as the guidelines for breast radiation boost after lumpectomy. Eur J Surg Oncol 25:483–486
Poortmans P, Bartelink H, Horiot J-C, Struikmans H, Van den Bogaert W, Fourquetf A, Jagerg J, Hoogenraadh W, Rodrigusa P, Rodenhuisi CW, Collette L, Pierartj M; On behalf of the EORTC Radiotherapy and Breast Cancer Groups, 2004, The influence of the boost technique on local control in breast conserving treatment in the EORTC ‘boost versus no boost’ randomised trial. Radiother Oncol 72:25–33
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 193
EP 197
DI 10.1007/s12253-008-9015-2
PG 5
ER
PT J
AU Rieker, JR
Hoegel, J
Kern, AM
Steger, Ch
Aulmann, S
Mechtersheimer, G
Schirmacher, P
Blaeker, H
AF Rieker, J Ralf
Hoegel, Josef
Kern, A Michael
Steger, Christina
Aulmann, Sebastian
Mechtersheimer, Gunhild
Schirmacher, Peter
Blaeker, Hendrik
TI A Mathematical Approach Predicting the Number of Events in Different Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Incidence rates; Mutations; Poisson distribution; Probabilities; Tumorigenesis
ID Incidence rates; Mutations; Poisson distribution; Probabilities; Tumorigenesis
AB Supported by different investigations, multi-step models for tumorigenesis have been proposed for epithelial tumors. The age specific incidence of some cancers shows an exponential rise with increasing patient age. Yet, the onset and the slope of incidence curves varies between tumor types. One simple explanation for this disparity is that the number of mutations required for transformation differs in various tissues. We used a homogeneous Poisson process to estimate the number of events (N) and the intensity or event rate (1) that might be needed for cancer development in various tissues (colon, prostate, oralpharynx, larynx). Estimations were performed, including 95% confidence intervals, for the male and female population. The expected number of events needed was higher in adenocarcinomas (colorectal carcinoma: N≈10 for females and N≈11.0 for males; prostatic cancer: N≈23) than in squamous cell carcinomas (oropharynx: N≈5–6 for females and N≈6 for males; larynx: N≈7 for females and N≈ 8 males). Still, alternative models fixing N to values within the 95% confidence intervals determined, showed good coincidence with epidemiological data. Although the herein applied mathematical model neglects several biologic conditions, especially a presumed acceleration of mutation rates after tumor initiation it offers a plausible theory for the given epidemiologic data and matches with molecular biologic findings in the investigated cancers.
C1 [Rieker, J Ralf] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Hoegel, Josef] University of Ulm, Department of Human GeneticsUlm, Germany.
[Kern, A Michael] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Steger, Christina] Medical University of Innsbruck, Department of PathologyInnsbruck, Austria.
[Aulmann, Sebastian] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Mechtersheimer, Gunhild] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Schirmacher, Peter] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
[Blaeker, Hendrik] University of Heidelberg, Department of Pathology, INF 220/221, 69120 Heidelberg, Germany.
RP Blaeker, H (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
EM hendrik.blaeker@med.uni-heidelberg.de
CR Hasty P, Campisi J, Hoeijmakers J et al, 2003, Aging and genome maintenance: lessons from the mouse? Science 299:1355–1359
Tomlinson I, Sasieni P, Bodmer W, 2002, How many mutations in a cancer? Am J Pathol 160:755–758
Fearon ER, Vogelstein B, 1990, A genetic model for colorectal tumorigenesis. Cell 61:759–767
Fischer JC, Hollomon JH, 1951, A hypothesis for the origin of cancer foci. Cancer 4:916–918
Nordling CO, 1953, A new theory on the cancer-inducing mechanism. Br J Cancer 7:68–72
Armitage P, Doll R, 1954, The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer 8:1–12
Armitage P, Doll R, 1957, A two-stage theory of carcinogenesis in relation to the age distribution of human cancer. Br J Cancer 11:161–169
Knudson AG, 1971, Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823
Knudson AG, 1973, Mutation and human cancer. Adv Cancer Res 17:317–352
Hazelton WD, Clements MS, Moolgavkar SH, 2005, Multistage carcinogenesis and lung cancer mortality in three cohorts. Cancer Epidemiol Biomarkers Prev 14:1171–1181
Breiman L, ed,, 1968, Probability. Wesley, Reading
Ries LAG, Eisner MP, Kosary CL et al, eds,, 2005, SEER Cancer Statistics Review, 1975–2002. National Cancer Institute, Bethesda. Accessed at http://seer.cancer.gov/csr/1975_2002/, based on November 2004 SEER data submission, posted to the SEER web site 2005. Cited 15 Jan 2007
Davies H, Bignell GR, Cox C et al, 2002, Mutations of the BRAF gene in human cancer. Nature 417:949–954
Yuen ST, Davies H, Chan TL et al, 2002, Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 62:6451–6455
Samuels Y, Velculescu VE, 2004, Oncogenic mutations of PIK3CA in human cancers. Cell Cycle 3:1221–1224
Wang Z, Shen D, Parsons DW, Bardelli A et al, 2004, Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304:1164–1166
Loeve F, Boer R, Zauber AG et al, 2004, National Polyp Study data: evidence for regression of adenomas. Int J Cancer 111:633– 639
Nwosu V, Carpten J, Trent JM et al, 2001, Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum Mol Genet 10:2313–2318
Karayi MK, Markham AF, 2004, Molecular biology of prostate cancer. Prostate Cancer Prostatic Dis 7:6–20
KimMM, Califano JA, 2004, Molecular pathology of head-and-neck cancer. Int J Cancer 112:545–553
Pai SI, Wu GS, Ozoren N et al, 1998, Rare loss-of-function mutation of a death receptor gene in head and neck cancer. Cancer Res 58:3513–3518
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 199
EP 204
DI 10.1007/s12253-008-9050-z
PG 6
ER
PT J
AU Belovejdov, V
Staribratova, D
Dikov, D
AF Belovejdov, Vesselin
Staribratova, Diana
Dikov, Dorian
TI Microscopic Peliosis of Pancreatic Islets Associated with Thrombotic Thrombocytopenic Purpura
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Disseminated intravascular coagulation; pancreas; Peliosis; Pancreatic islets; Thrombocytic thrombocytopenic purpura
ID Disseminated intravascular coagulation; pancreas; Peliosis; Pancreatic islets; Thrombocytic thrombocytopenic purpura
AB Peliosis is a rarely seen histological finding with unexplained fully etiology and pathogenesis. It is presented as cyst-like blood filled cavities. The presence of peliosis in the endocrine part of the pancreas is extremely rarely reported microscopic phenomenon. The authors provide histological, histochemical, immunohistochemical and ultrastructural investigation of microscopic peliosis in the pancreas from an autopsy case with thrombotic trombocytopenic purpura. The findings give ideas for a wide range of pathophysiological and morphogenetic comments of such an unusual morphologic presentation.
C1 [Belovejdov, Vesselin] Medical University of Plovdiv, Department of General and Clinical PathologyPlovdiv, Bulgaria.
[Staribratova, Diana] Medical University of Plovdiv, Department of General and Clinical PathologyPlovdiv, Bulgaria.
[Dikov, Dorian] Centre Hospitalier de Lagny-Marne-La-Vallee, Service d’Anatomie et de Cytologie PathologiquesParis, France.
RP Staribratova, D (reprint author), Medical University of Plovdiv, Department of General and Clinical Pathology, Plovdiv, Bulgaria.
EM dianastar@abv.bg
CR Corpa MVN, Bacchi MM, Bacchi CE et al, 2004, Peliosis hepatis associated with lymphoplasmacytic lymphoma. Arch Pathol Lab Med 128:1283–1285
Kovacs K, Horvath E, Asa S et al, 1986, Microscopic peliosis of pancreatic islets in a woman with MEN-1 syndrome. Arch Pathol Lab Med 110:607–610
Berzigotti A, Magalotti D, Zappoli P et al, 2006, Peliosis hepatic as an early histological finding in idiopathic portal hypertension: a case report. World J Gastroenterol 12(22):3612– 3615
Tsokos M, Erbersdobler A, 2005, Pathology of peliosis. Forensic Sci Int 149, 1):25–33
Zafrani ES, Cazier A, Baudelot AM et al, 1984, Ultrastructural lesions of the liver in human peliosis. A report of 12 cases. Am J Pathol 114(3):349–359
Warfel KA, Ellis GH, 1982, Peliosis of the spleen. Report of a case and review of the literature. Arch Pathol Lab Med 106(2):99– 100
Czapar CA, Weldon-Linne CM, Moore DM et al, 1986, Peliosis hepatic in acquired immunodeficiency syndrome. Arch Pathol Lab Med 110(7):611–613
Gulubova M, 2002, Immunohistochemical localization of collagen Type III and Type IV, laminin, tenascin and α-smooth muscle actin, αSMA, in the human liver in peliosis. Pathol Res Pract 198:803–812
Korner M, Gebbers J-O, 2002, Peliosis of the spleen and haemolytic anemia. Histopathology 41:179–180
Koehler JE, Sanchez MA, Garrido CS et al, 1997, Molecular epidemiology of Bartonellainfections in patients with bacillary angiomatosis–peliosis. The N Eng J Med 337, 26):1876–83
Coire CI, Horvath E, Kovacs K et al, 1997, Cushing’s syndrome from an ectopic pituitary adenoma with peliosis: a histological, immunohistochemical and ultrastructural study and review of the literature. Endocr Pathol 8(1):65–74
Lie JT, 1985, Pulmonary peliosis. Arch Pathol Lab Med 109, 9):878–9
Chetty R, Kennedy M, Ezzat S et al, 2004, Pancreatic endocrine pathology in von Hippel-Lindau disease: an expanding spectrum of lesions. Endocrine Pathology 15(2):141–148
Pernicone PJ, Lie JT, 1987, Isolated peliosis of pancreatic islet cell adenoma. Arch Pathol Lab Med 111:690–691
Ricketts LM, Dlugous M, Luther KB et al, 2007, O-fucosylation is require for ADAMTS 13 secretion. J Biol Chem 282, 23):17014–23
Girma JP, 2006, Biology of von Willebrand factor. Nephrol Ther 2:s143–s148
Fina L, Molgaard HV, Robertson D et al, 1990, Expression of the CD 34 gene in vascular endothelial cells. Blood 75, 12):2417–26
Delas N, Faurel JP, Wechsled B et al, 1982, Association of peliosis and necrotizing vasculitis. Nouv Presse Med 25;11, 37):2787
Galbusera M, Noris M, Remuzzi G, 2006, Thrombotic thrombocytopenic purpura—then and now. Semin Thromb Hemost 32, 2):81–89
Voinchet O, Degott C, Scoazec JY et al, 1988, Peliosis hepatis, nodular regenerative hyperplasia of the liver, and light-chain deposition in a patient with Waldenstrom’s macroglobulinemia. Gastroenterology 95:482–486
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 205
EP 208
DI 10.1007/s12253-008-9048-6
PG 4
ER
PT J
AU Maka, E
Lukats, O
Toth, J
Fekete, S
AF Maka, Erika
Lukats, Olga
Toth, Jeannette
Fekete, Sandor
TI Orbital Tumour as Initial Manifestation of Acute Myeloid Leukemia: Granulocytic Sarcoma: Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Orbital granulocytic sarcoma; Acute myeloid leukemia
ID Orbital granulocytic sarcoma; Acute myeloid leukemia
AB We report orbital involvement as an initial manifestation of acute myeloid leukemia in a 57-year-old woman. The patient presented with painful proptosis and limited ocular motility. Orbital computed tomography revealed bilateral homogeneous masses. Orbital biopsy was performed on the right side; and histopathology disclosed a myelocytic tumour. Despite treatment using irradiation and chemotherapy, the patient died eleven months after presentation. There appear to be only a few previous reports of acute myeloid leukemia cases presenting with orbital involvement, and most cases occurred in children. This very rare condition has a poor survival prognosis, even with radiation treatment and chemotherapy.
C1 [Maka, Erika] Semmelweis University, Department of Ophthalmology, Tomo utca 25–29, 1083 Budapest, Hungary.
[Lukats, Olga] Semmelweis University, Department of Ophthalmology, Tomo utca 25–29, 1083 Budapest, Hungary.
[Toth, Jeannette] Semmelweis University, Department of Ophthalmology, Tomo utca 25–29, 1083 Budapest, Hungary.
[Fekete, Sandor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Maka, E (reprint author), Semmelweis University, Department of Ophthalmology, 1083 Budapest, Hungary.
EM maker@szem1.sote.hu
CR Zimmerman LE, Font RL, 1975, Ophthalmologic manifestations of granulocytic sarcoma, myeloid sarcoma or chloroma). Am J Ophthalmol 80:975–989
Bhattacharjee K, Bhattacharjee H, Das D, Babu K, Mahesh L, Krishnakumar S, Biswas J, 2003, Chloroma of the orbit in a nonleukemic adult: a case report. Orbit 22:293–297
Kincaid MC, Green WR, 1983, Ocular and Orbital Involvement in Leukemia. Surv Ophthalmol 27:211–232
Padillo D, Mencia E, Gutierrez E, Martinez MA, 1999, Orbital granulocytic sarcoma in a myelodysplastic syndrome. Orbit 18: 287–290
Stockl FA, DolmetschAM, SaornilMA, Font RL, BurnierMN, 1997, Orbital granulocytic sarcoma. Br J Ophthalmol 81:1084–1088
Watkins LM, Remulla HD, Rubin PAD, 1997, Orbital granulocytic sarcoma in an elderly patient. Am J Ophthalmol 123:854–856
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 209
EP 211
DI 10.1007/s12253-008-9028-x
PG 3
ER
PT J
AU Leoncini, G
Maio, V
Puccioni, M
Franchi, A
De Giorgi, V
Ucci, F
Santucci, M
Massi, D
AF Leoncini, Giuseppe
Maio, Vincenza
Puccioni, Marco
Franchi, Alessandro
De Giorgi, Vincenzo
Ucci, Francesca
Santucci, Marco
Massi, Daniela
TI Orbital Solitary Fibrous Tumor: A Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Solitary fibrous tumor; Orbit
ID Solitary fibrous tumor; Orbit
AB Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm typically arising in the pleura and involving the orbit as its most common extra-pleural location. We herein describe a well documented case of orbital SFT arising in a 62-year-old woman presenting with progressive swelling of the right upper eyelid and proptosis. The tumor had a benign clinical course, with radical surgical excision followed by regression of the clinical symptoms. We review the clinical, histopathological, and immunohistochemical features of the orbital SFT described so far, with particular emphasis on differential diagnosis with other spindle cell orbital neoplasms.
C1 [Leoncini, Giuseppe] AOU Careggi, Department of Human Pathology and Oncology, Viale GB Morgagni 85, 50134 Florence, Italy.
[Maio, Vincenza] AOU Careggi, Department of Human Pathology and Oncology, Viale GB Morgagni 85, 50134 Florence, Italy.
[Puccioni, Marco] University of Florence, Department of OphthalmologyFlorence, Italy.
[Franchi, Alessandro] AOU Careggi, Department of Human Pathology and Oncology, Viale GB Morgagni 85, 50134 Florence, Italy.
[De Giorgi, Vincenzo] University of Florence, Department of Dermatological SciencesFlorence, Italy.
[Ucci, Francesca] University of Florence, Department of OphthalmologyFlorence, Italy.
[Santucci, Marco] AOU Careggi, Department of Human Pathology and Oncology, Viale GB Morgagni 85, 50134 Florence, Italy.
[Massi, Daniela] AOU Careggi, Department of Human Pathology and Oncology, Viale GB Morgagni 85, 50134 Florence, Italy.
RP Massi, D (reprint author), AOU Careggi, Department of Human Pathology and Oncology, 50134 Florence, Italy.
EM Daniela.massi@unifi.it
CR De Saint Aubain Somerhausen N, Rubin BP, Fletcher CDM, 1999, Mixoid solitary fibrous tumor: a study of seven cases with emphasis on differential diagnosis. Mod Pathol 12:463–471
Klemper C, Rabin CB, 1931, Primary neoplasm of the pleura; a report of five cases. Arch Pathol 11:385–412
El-Naggar AK, Ro JY, Ayala AG et al, 1989, Localized fibrous tumor of the serosal cavities. Am J Clin Pathol 13:199–209
Kottke-Marchant K, Hart WR, Broughan T, 1989, Localized fibrous tumor, localized fibrous mesothelioma, of the liver. Cancer 64:1096–1102
Witkin GB, Rosai J, 1989, Solitary fibrous tumor of the mediastinum. Am J Surg Pathol 13:547–557
Witkin GB, Rosai J, 1991, Solitary fibrous tumor of the upper respiratory tract. Am J Surg Pathol 15:842–848
Fukunaga M, Nikaido T, 1997, Solitary fibrous tumor of the renal peri-pelvis. Histopathology 30:451–456
Prevot S, Penna C, Imbert JC et al, 1996, Solitary fibrous tumor of the adrenal gland. Mod Pathol 9:1170–1174
Fisher C, Bisceglia M, 1994, Solitary fibrous tumor of the spermatic cord. Br J Urol 74:798–789
Hasegawa T, Hirose T, Seki K et al, 1996, Solitary fibrous tumor of the soft tissue. Am J Clin Pathol 106:325–331
Cowper SE, Kilpatrick T, Proper S et al, 1999, Solitary fibrous tumor of the skin. Am J Dermatopathol 21(3):213–219
Zuckerberg ML, Rosemberg AE, Randolph G et al, 1991, Solitary fibrous tumor of the nasal cavity and paranasal sinuses. Am J Surg Pathol 15:126–130
England DM, Hochholzer L,McCarthyMJ, 1989, Localized benign and malignant fibrous tumors of the pleura: a clinicopathologic review of 223 cases. Am J Surg Pathol 13:640–658
Chan JKC, 1997, Solitary fibrous tumor—everywhere and a diagnosis in vogue. Histopathology 31:568–576
Frederick A Font J, Font RL, 1986, Orbit. In: Spencer WH, ed, Ophthalmic pathology: an atlas and textbook, 3rd edn. Saunders, Philadelphia, pp 2459–2860
Festa S, Lee HJ, Langer P et al, 1999, Solitary fibrous tumor of the orbit: CT and pathologic correlation. Neuroradiology 41:52–54
Scott IU, Tanenbaum M, Rubin D et al, 1996, Solitary fibrous tumor of the lacrimal gland fossa. Ophthalmology 103:1613– 1618
Woo KI, Suh YL, Kim YD, 1999, Solitary fibrous tumor of the lacrimal sac. Ophthal Plast Reconstr Surg 15(6):450–453
Polito E, Tosi M, Toti P et al, 2002, Orbital solitary fibrous tumor with aggressive behaviourThree cases and review of the literature. Graefes Arch Clin Exp Ophthalmol 240(7):570–574
Hayashi S, Kurihara H, Hirato J et al, 2001, Solitary fibrous tumor of the orbit with an extraorbital extension: case report. Neurosurgery 49(5):1241–1245
Carrera M, Prat J, Quintana M, 2001, Malignant solitary fibrous tumor of the orbit: report of a case with 8 years follow-up. Eye 15:102–104
Vallat-Decouvelaere AV, Dry SM, Fletcher CDM, 1998, Atypical and malignant solitary fibrous tumors in extra-thoracic locations. Evidence of their comparability to intra-thoracic tumors. Am J Surg Pathol 22:1501–1511
Hasegawa T, Matsuno Y, Shimoda T et al, 1999, Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behaviour. Hum Pathol 30:1464–1473
Enzinger FM, Weiss SW, 1997, Soft tissue tumors, 4th edn. Mosby, USA
Moran CA, Suster S, Koss MN, 1992, The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura. Sem Diagn Pathol 9:169–180
Nielsen GP, O’Connell JX, Dickersin GR et al, 1997, Solitary fibrous tumor of soft tissue. A report of 15 cases, including 5 malignant examples with light microscopic, immunohistochemical, and ultrastructural data. Mod Pathol 10:1028–1037
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2008
VL 14
IS 2
BP 213
EP 217
DI 10.1007/s12253-008-9055-7
PG 5
ER
PT J
AU Deli, T
Csernoch, L
AF Deli, Tamas
Csernoch, Laszlo
TI Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Extracellular ATP; P2 purinergic receptors; Cancer; Proliferation; Differentiation; Apoptosis
ID Extracellular ATP; P2 purinergic receptors; Cancer; Proliferation; Differentiation; Apoptosis
AB Purinergic signal transduction mechanisms have been appreciated as a complex intercellular signalling network that plays an important regulatory role in both short- and long-term processes in practically every living cell. One of the most intriguing aspects of the field is the participation of ATP and other purine nucleotides in the determination of cell fate and the way they direct cells towards proliferation, differentiation or apoptosis, thereby possibly taking part in promoting or preventing malignant transformation. In this review, following a very brief introduction to the historical aspects of purinergic signalling and a concise overview of the structure of and signal transduction pathways coupled to P2 purinergic receptors, the current theories concerning the possible ways how extracellular ATP can alter the function of tumour cells and the effectiveness of anticancer therapies are discussed, including pharmacological, nutritional, vasoactive and ‘anti-antioxidant’ actions of the nucleotide. The effects of ATP on animals inoculated with human tumours and on patients with cancer are looked over next, and then an overview of the literature regarding the expression and presumed functions of P2 purinoceptors on tumour cells in vitro is presented, sorted out according to the relevant special clinical fields. The article is closed by reviewing the latest developments in the diagnostic use of P2 purinergic receptors as tumour markers and prognostic factors, while discussing some of the difficulties and pitfalls of the therapeutic use of ATP analogues.
C1 [Deli, Tamas] University of Debrecen, Faculty of Medicine, Department of Physiology, 98 Nagyerdei krt., 4012 Debrecen, Hungary.
[Csernoch, Laszlo] University of Debrecen, Faculty of Medicine, Department of Physiology, 98 Nagyerdei krt., 4012 Debrecen, Hungary.
RP Csernoch, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Physiology, 4012 Debrecen, Hungary.
EM csl@phys.dote.hu
CR Drury AN, Szent-Gyorgyi A, 1929, The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. J Physiol 68:213–237
Holton P, 1959, The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol, Lond, 145:494–504
Martinson J, Muren A, 1963, Excitatory and inhibitory effects of vagus stimulation on gastric motility in the cat. Acta Physiol Scand 57:309–316
BurnstockG, 1972, Purinergic nerves. Pharmacol Rev 24:509–581
Burnstock G, 1978, A basis for distinguishing two types of purinergic receptor. In: Straub RW and Bolis L, eds, Cell membrane receptors for drugs and hormones: a multidisciplinary approach. Raven, New York, pp 107–118
Burnstock G, Kennedy C, 1985, Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440
Lazarowski E, 2006, Regulated release of nucleotides and UDP sugars from astrocytoma cells. Novartis Found Symp 276:73–84 discussion 84–90, 107–12, 275–81
Selzner N, Selzner M, Graf R, Ungethuem U, Fitz JG, Clavien PA, 2004, Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. Cell Death Differ Suppl 2:S172–180
Mazurek S, Boschek CB, Eigenbrodt E, 1997, The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. J Bioenerg Biomembranes 29(4):315–330
Zimmermann H, 2001, Ectonucleotidases: some recent developments and a note on nomenclature. Drug Dev Res 52:44–56
Bavaresco L, Bernardi A, Braganhol E, Wink MR, Battastini AM, 2007, Dexamethasone inhibits proliferation and stimulates ecto-5′-nucleotidase/CD73 activity in C6 rat glioma cell line. J Neurooncol 84(1):1–8
Kunzli BM, Berberat PO, Giese T, Csizmadia E, Kaczmarek E, Baker C, Halaceli I, Buchler MW, Friess H, Robson SC, 2007, Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease. Am J Physiol Gastrointest Liver Physiol 292, 1):G223–G230
Jackson SW, Hoshi T, Wu Y, Sun X, Enjyoji K, Csizmadia E, Sundberg C, Robson SC, 2007, Disordered purinergic signaling inhibits pathological angiogenesis in cd39/Entpd1-null mice. Am J Pathol 171(4):1395–1404
Merighi S, Mirandola P, Varani K, Gessi S, Leung E, Baraldi PG, Tabrizi MA, Borea PA, 2003, A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol Ther 100(1): 31–48
North RA, 2002, Molecular physiology of P2X receptors. Physiol Rev 82(4):1013–1067
Bean BP, 1992, Pharmacology and electrophysiology of ATPactivated ion channels. Trends Pharmacol Sci 13(3):87–90
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 219
EP 231
DI 10.1007/s12253-008-9071-7
PG 13
ER
PT J
AU Morgenstern, D
Rees, H
Sebire, N
Shipley, J
Anderson, J
AF Morgenstern, A. Daniel
Rees, Helen
Sebire, J. Neil
Shipley, Janet
Anderson, John
TI Rhabdomyosarcoma Subtyping by Immunohistochemical Assessment of Myogenin: Tissue Array Study and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rhabdomyosarcoma; Myogenin; Tissue array; Diagnosis
ID Rhabdomyosarcoma; Myogenin; Tissue array; Diagnosis
AB Myogenin immunostaining has been described as a useful marker of the alveolar subtype of rhabdomyosarcoma and as a tool for distinguishing it from the more common embryonal subtype. To add to the growing body of literature describing this phenomenon we analysed myogenin immunohistochemical staining in 152 tumors using a rhabdomyosarcoma tissue array. Results were analysed blinded to histological type by two independent investigators. Samples were excluded if any samples failed to stain with desmin and/or myogenin. Mean percentage of myogenin positive cells was significantly greater for ARMS (n=31; mean percentage positivity 59% (95% confidence intervals ± 7%) than ERMS (n=41, mean percentage positivity 16%, 95% confidence intervals ± 4; P<0.0001). This data is consistent with previously published studies identifying strong nuclear myogenin staining in a high proportion of cells as a marker of alveolar histology.
C1 [Morgenstern, A. Daniel] Institute of Child Health, Unit of Molecular Haematology and Cancer Biology, 30 Guilford Street, WC1N 1EH London, UK.
[Rees, Helen] Institute of Child Health, Unit of Molecular Haematology and Cancer Biology, 30 Guilford Street, WC1N 1EH London, UK.
[Sebire, J. Neil] Great Ormond Street Hospital for Children, Department of HistopathologyLondon, UK.
[Shipley, Janet] Intsitute of Cancer Research, Department of Molecular CytogeneticsSutton, Surrey, UK.
[Anderson, John] Institute of Child Health, Unit of Molecular Haematology and Cancer Biology, 30 Guilford Street, WC1N 1EH London, UK.
RP Anderson, J (reprint author), Institute of Child Health, Unit of Molecular Haematology and Cancer Biology, WC1N 1EH London, UK.
EM j.Anderson@ich.ul.ac.uk
CR McManus AP, O'Reilly MA, Jones KP, Gusterson BA, Mitchell CD, Pinkerton CR, Shipley JM, 1996, Interphase fluorescence in situ hybridization detection of t(2;13)(q35;q14, in alveolar rhabdomyosarcoma–a diagnostic tool in minimally invasive biopsies. J Pathol 178:410–414
Sapi Z, Antal I, Papai Z, Szendroi M, Mayer A, Jakab K, Pajor L, Bodo M, 2002, Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques. Diagn Cytopathol 26:232–242
Anderson J, Gordon T, McManus A, Mapp T, Gould S, Kelsey A, McDowell H, Pinkerton R, Shipley J, Pritchard-Jones K, 2001, Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome? Br J Cancer 85:831–835
Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG, 2002, PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 20:2672–2679
Sebire NJ, Malone M, 2003, Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas. J Clin Pathol 56:412–416
Wachtel M, Runge T, Leuschner I, Stegmaier S, Koscielniak E, Treuner J, Odermatt B, Behnke S, Niggli FK, Schafer BW, 2006, Subtype and prognostic classification of rhabdomyosarcoma by immunohistochemistry. J Clin Oncol 24:816–822
Cessna MH, Zhou H, Perkins SL, Tripp SR, Layfield L, Daines C, Coffin CM, 2001, Are myogenin and myoD1 expression specific for rhabdomyosarcoma? A study of 150 cases, with emphasis on spindle cell mimics. Am J Surg Pathol 25:1150–1157
Wang NP, Marx J, McNutt MA, Rutledge JC, Gown AM, 1995, Expression of myogenic regulatory proteins, myogenin and MyoD1, in small blue round cell tumors of childhood. Am J Pathol 147:1799–1810
Folpe AL, 2002, MyoD1 and myogenin expression in human neoplasia: a review and update. Adv Anat Pathol 9:198–203
Kumar S, Perlman E, Harris CA, Raffeld M, Tsokos M, 2000, Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues. Mod Pathol 13:988–993
Hostein I, Andraud-Fregeville M, Guillou L, Terrier-Lacombe MJ, Deminiere C, Ranchere D, Lussan C, Longavenne E, Bui NB, Delattre O, Coindre JM, 2004, Rhabdomyosarcoma: value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype: an analysis of 109 paraffin-embedded specimens. Cancer 101:2817–2824
Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S, Wu C, Li X, Thompson J, Parham D, Qualman S, Houghton P, 2000, Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. Am J Pathol 156:399–408
Morotti RA, Nicol KK, Parham DM, Teot LA, Moore J, Hayes J, Meyer W, Qualman SJ, 2006, An immunohistochemical algorithm to facilitate diagnosis and subtyping of rhabdomyosarcoma: the Children's Oncology Group experience. Am J Surg Pathol 30:962–968
Stevens MC, Rey A, Bouvet N, Ellershaw C, Flamant F, Habrand JL, Marsden HB, Martelli H, Sanchez de Toledo J, Spicer RD, Spooner D, Terrier-Lacombe MJ, van Unnik A, Oberlin O, 2005, Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology–SIOP Malignant Mesenchymal Tumor 89. J Clin Oncol 23:2618–2628
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 233
EP 238
DI 10.1007/s12253-008-9012-5
PG 6
ER
PT J
AU Dova, L
Golfinopoulos, V
Pentheroudakis, G
Georgiou, I
Pavlidis, N
AF Dova, Lefkothea
Golfinopoulos, Vassilis
Pentheroudakis, George
Georgiou, Ioannis
Pavlidis, Nicholas
TI Systemic Dissemination in Cancer of Unknown Primary is Independent of Mutational Inactivation of the KiSS-1 Metastasis-suppressor Gene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CUP; KiSS-1 metastasis-suppressor gene; Polymerase chain reaction; KiSS-1; FFPE
ID CUP; KiSS-1 metastasis-suppressor gene; Polymerase chain reaction; KiSS-1; FFPE
AB Cancer of unknown primary represents a heterogeneous group of malignancies characterised by early systemic dissemination and lack of primary site. KiSS1 is a member of the metastasis-suppressor gene family whose functional role is being investigated in human malignancies. We extracted DNA from 50 paraffin-embedded unknown primary tumors and screened KiSS1 exons III and IV for presence of mutations by means of Single Strand Conformational Polymorphism and direct sequencing. Only one tumor specimen harboured a cytosine to guanine point substitution in base 242 of exon IVa, resulting in a proline to arginine switch at codon 81 of the KiSS1 protein (P81R). The remaining 49 tumors harbored wild-type KiSS1 alleles, indistinguishable from those of peripheral blood lymphocytes of 50 healthy controls. Consequently, the propensity for systemic spread of unknown primary tumors may by due to mutations in genes other than KiSS1 or aberrant epigenetic regulation.
C1 [Dova, Lefkothea] Ioannina University Hospital, Hematological LaboratoryIoannina, Greece.
[Golfinopoulos, Vassilis] Ioannina University Hospital, Department of Medical OncologyIoannina, Greece.
[Pentheroudakis, George] Ioannina University Hospital, Department of Medical OncologyIoannina, Greece.
[Georgiou, Ioannis] Ioannina University Hospital, Department of Obstetrics and GynecologyIoannina, Greece.
[Pavlidis, Nicholas] Ioannina University Hospital, Department of Medical OncologyIoannina, Greece.
RP Pavlidis, N (reprint author), Ioannina University Hospital, Department of Medical Oncology, Ioannina, Greece.
EM npavlid@cc.uoi.gr
CR Yoshida BA, Sokoloff M, Welch DR, Rinker-Schaeffer CW, 2000, Metastasis-suppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst 92:1717–1730
West A, Vojta PJ, Welch DR, Weissman BE, 1998, Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene, KISS1). Genomics 54:145–148
Nash KT, Welch DR, 2006, The KISS1 metastasis suppressor: mechanistic insights and clinical utility. Front Biosci 11:647– 659
Pentheroudakis G, Kostadima L, Dova L, Malamou-Mitsi V, Georgiou I et al, 2006, The missing kiss of life: Analysis of mutation and protein expression of the metastasis-suppressor gene KISS1 in early breast cancer. Ann Oncol 17(Suppl 9):ix59, 101P)
Pentheroudakis G, Briasoulis E, Pavlidis N, 2007, Cancer of unknown primary site: missing primary or missing biology? Oncologist 12:418–425
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 239
EP 241
DI 10.1007/s12253-008-9024-1
PG 3
ER
PT J
AU Mojica, DW
Stein, L
Hawthorn, L
AF Mojica, D Wilfrido
Stein, Leighton
Hawthorn, Lesleyann
TI Universal Reference RNA is Not a Representative Normal Sample for Oligonucleotide Microarray Studies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Reference RNA; Oligonucleotide expression microarray; Experimental bias
ID Reference RNA; Oligonucleotide expression microarray; Experimental bias
AB Translational research has been defined as the scientific study using human material that will ultimately generate patient specific data. A major caveat in human directed study is the availability of high quality and quantities of patient derived homogeneous cells for analysis. Whereas there exist sources for which tumor tissue and blood samples can be made available, the same cannot be said for normal tissue. The absence of normal control tissue has led to the creation of pooled cell lines and tissues for purchase known as "reference RNA". Although initially created for purposes of standardization, the difficulty associated with acquiring normal tissue has led some investigators to use sources of universal pooled RNA for comparative analysis with clinical tissue specimens. In order to study the effects of using Universal Reference RNA on expression profiling experiments we have evaluated the performance of universal RNA compared to RNA obtained from a purified population of colon epithelial cells in defining a set of altered transcripts in colon cancer.
C1 [Mojica, D Wilfrido] State University of New York, University at Buffalo, Department of Pathology, 100 High Street, 14203 Buffalo, NY, USA.
[Stein, Leighton] Roswell Park Cancer Institute, Gene Expression Facility, Elm and Carlton Streets, 14263 Buffalo, NY, USA.
[Hawthorn, Lesleyann] Roswell Park Cancer Institute, Gene Expression Facility, Elm and Carlton Streets, 14263 Buffalo, NY, USA.
RP Mojica, DW (reprint author), State University of New York, University at Buffalo, Department of Pathology, 14203 Buffalo, USA.
EM mojica@buffalo.edu
CR van’t Veer LJ, Paik S, Hayes DF, 2005, Gene expression profiling of breast cancer: a new tumor marker. J Clin Oncol 23(8):1631– 1635
Cronin M, Ghosh K, Sistare F, Quakenbush J, Vilker V, O’Connell C, 2004, Universal RNA reference materials for gene expression. Clin Chem 50:1464–1471
Cowell JK, Hawthorn L, 2007, The application of microarray technology to the analysis of the cancer genome. Curr Mol Med 7, 1):103–120
Novoradovskaya N, Whitfield ML, Basehore LS et al, 2005, Universal reference RNA as a standard for microarray experiments. BMC Genom 5:20
Schlecht NF, Burk RD, Adrien L et al, 2007, Gene expression profiles in HPV-infected head and neck cancer. J Pathol 213:283– 293
Larsen JE, Pavey SJ, Passmore LH et al, 2007, Expression profiling defines a recurrence signature in lung squamous cell carcinoma. Carcinogenesis 28(3):760–766
Bianchi F, Hu J, Pelosi G et al, 2004, Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray. Clin Cancer Res 10:6023–6028
Warner GC, Reis PP, Jurisica I et al, 2004, Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis. Int J Cancer 110:857–868
Mojica WD, Arshad A, Sharma S et al, 2006, Manual exfoliation plus immunomagnetic bead separation as an initial step toward translational studies. Arch Pathol Lab Med 130(1):74–79
Mojica WD, Stein L, Hawthorn L, 2007, An exfoliation and enrichment strategy results in improved transcriptional profiles when compared to matched formalin fixed samples. BMC Clin Pathol 7:7
Hawthorn L, Stein L, Panzarella J et al, 2006, Characterization of cell-type specific profiles in tissues and isolated cells from squamous cell carcinomas of the lung. Lung Cancer 53(2):129– 142
Irizarry RA, Hobbs B, Collin F et al, 2003, Exploration, normalization, and summaries of high-density oligonucleotide array probe level data. Biostatistics 4:249–264
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Nielssen TO, West RB, Linn SC et al, 2002, Molecular characterization of soft tissue tumours: a gene expression study. Lancet 359:1301–1307
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Demichelis F, Gruelich H, Macoska JA et al, 2007, SNP panel identification assay, SPIA): a genetic-based assay for the identification of cell lines. Mod Pathol 20(S2):346A, abstract)
Celis A, Rasmussen HH, Celis P et al, 1999, Short term culturing of low grade superficial bladder transitional cell carcinoma leads to changes in the expression levels of several proteins involved in key cellular activities. Electrophoresis 20:355–361
Somel M, Khaitovich P, Bahn S et al, 2006, Gene expression becomes heterogeneous with age. Curr Biol 16(10):R359–360
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 243
EP 251
DI 10.1007/s12253-008-9068-2
PG 9
ER
PT J
AU Reiner-Concin, A
Regitnig, P
Dinges, PH
Hofler, G
Lax, S
Muller-Holzner, E
Obrist, P
Rudas, M
AF Reiner-Concin, Angelika
Regitnig, Peter
Dinges, Peter Hans
Hofler, Gerald
Lax, Sigurd
Muller-Holzner, Elisabeth
Obrist, Peter
Rudas, Margaretha
TI Practice of HER-2 Immunohistochemistry in Breast Carcinoma in Austria
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; HER-2; Immunohistochemistry; Quality assurance; Reproducibility
ID Breast cancer; HER-2; Immunohistochemistry; Quality assurance; Reproducibility
AB Practice and accuracy of immunohistochemistry is known to vary highly. Reliability of HER-2 immunohistochemistry is critical because of its role in patient selection for therapeutical options in breast cancer. Therefore reliability of HER-2 immunohistochemistry in pathology laboratories in Austria was assessed. Ten tissue specimens of invasive ductal breast carcinomas and three cell line samples were tested. Presence/absence of gene amplification was determined by FISH to be used as a gold standard. Laboratories were asked to stain and assess slides using their routine immunohistochemical staining protocol. Overall the study consisted of 311 tests on tissue specimens and 142 on cell lines. In all cases manual scoring was performed. Participation was voluntary and was 94%. Overall sensitivity was 90.5% and specificity 99.2%. Overscoring including true false positive results were found in 6.7% and 6.3% in tissue specimens and cell lines, respectively. False negative determinations were obtained in 1.9% and 2.8% of tissue specimens and cell lines, respectively. HercepTestTM showed slightly higher reliability in comparison with individualized staining methods. By manual scoring inaccurate scoring affected 12.3% of test results and 62% of the laboratories. In conclusion participation rate and accuracy of HER-immunohistochemistry was high all over the country. Manually performed scoring demonstrated some limitations.
C1 [Reiner-Concin, Angelika] Donauspital, Pathologisch-Bakteriologisches InstitutVienna, Austria.
[Regitnig, Peter] Medical University of Graz, Department of PathologyGraz, Austria.
[Dinges, Peter Hans] Hospital Klagenfurt, Department of PathologyKlagenfurt, Austria.
[Hofler, Gerald] Medical University of Graz, Department of PathologyGraz, Austria.
[Lax, Sigurd] LKH-West Graz, Department of PathologyGraz, Austria.
[Muller-Holzner, Elisabeth] Medical University of Innsbruck, Department of Obstetrics and GynecologyInnsbruck, Austria.
[Obrist, Peter] Pathohistological LaboratoryLandeck, Austria.
[Rudas, Margaretha] Medical University of Vienna, Department of PathologyVienna, Austria.
RP Reiner-Concin, A (reprint author), Donauspital, Pathologisch-Bakteriologisches Institut, Vienna, Austria.
EM angelika.reiner@wienkav.at
CR Wolff AC, Hammond ME, Schwartz JN et al, 2007, American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18– 43
Gennari A, Sormani MP, Pronzato P et al, 2008, HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100:14–20
Yamauchi H, Stearns V, Hayes DF, 2001, When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 19:2334–2356
Konecny G, Pauletti G, Pegram M et al, 2003, Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 95:142–153
Menard S, Valagussa P, Pilotti S et al, 2001, Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables. J Clin Oncol 19:329–335
Press MF, Hung G, Godolphin Wet al, 1994, Sensitivity of HER- 2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. Cancer Res 54:2771–2777
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ItalianNetwork forQuality Assurance of Tumor Biomarkers, INQAT, Group; SIAPEC-IAP, 2005, Interobserver reproducibility of immunohistochemical HER-2/neu assessment in human breast cancer: an update from INQAT round III. Int J Biol Markers 20:189–194
Paik S, Bryant J, Tan-Chiu E et al, 2002, Real-world performance of HER2 testing—National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst 94:852–854
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 253
EP 259
DI 10.1007/s12253-008-9079-z
PG 7
ER
PT J
AU Caner, V
Turk, SN
Duzcan, F
Satiroglu-Tufan, L
Kelten, CE
Zencir, S
Dodurga, Y
Bagci, H
Duzcan, ES
AF Caner, Vildan
Turk, Sen Nilay
Duzcan, Fusun
Satiroglu-Tufan, Lale
Kelten, Canan Esra
Zencir, Sevil
Dodurga, Yavuz
Bagci, Huseyin
Duzcan, Ender Suleyman
TI No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FISH; HER-2/neu; Immunohistochemistry; Real-time quantitative PCR; urothelial carcinoma
ID FISH; HER-2/neu; Immunohistochemistry; Real-time quantitative PCR; urothelial carcinoma
AB The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.
C1 [Caner, Vildan] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Turk, Sen Nilay] Pamukkale University, Faculty of Medicine, Department of Pathology, 20020 Denizli, Turkey.
[Duzcan, Fusun] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Satiroglu-Tufan, Lale] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Kelten, Canan Esra] Pamukkale University, Faculty of Medicine, Department of Pathology, 20020 Denizli, Turkey.
[Zencir, Sevil] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Dodurga, Yavuz] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Bagci, Huseyin] Pamukkale University, Medical Faculty, Department of Medical Biology, 20020 Denizli, Turkey.
[Duzcan, Ender Suleyman] Pamukkale University, Faculty of Medicine, Department of Pathology, 20020 Denizli, Turkey.
RP Duzcan, ES (reprint author), Pamukkale University, Faculty of Medicine, Department of Pathology, 20020 Denizli, Turkey.
EM eduzcan@yahoo.com
CR Latif Z, Watters AD, Dunn I et al, 2004, HER2/neu gene amplification and protein overexpression in G3 pT2 transitional cell carcinoma of the bladder: a role for anti-HER2 therapy? Eur J Cancer 40:56–63
Morrison C, Zanagnolo V, Ramirez N et al, 2006, HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol 24:2376–2385
Ross JS, Fletcher JA, Linette GP et al, 2003, The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 8:307–325
Schraml P, Kononen J, Bubendorf L et al, 1999, Tissue microarrays for gene amplification surveys in many different tumor types. Clin Cancer Res 5:1966–1975
Kruger S, Weitsch G, Buttner H et al, 2002, Overexpression of cerbB- 2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. Int J Oncol 21:981–987
Underwood M, Barlett J, Reeves J et al, 1995, c-erbB-2 gene amplification: a molecular marker in recurrent bladder tumors? Cancer Res 55:2422–2430
Bartlett J, Mallon E, Cooke T, 2003, The clinical evaluation of HER-2 status: which test to use? J Pathol 199:411–417
Langner C, Gross C, Rehak P et al, 2005, HER2 protein overexpression and gene amplification in upper urinary transitional cell carcinoma: systematic analysis applying tissue microarray technique. Urology 65:176–180
Bast RCJ, Ravdin P, Hayes DF et al, 2001, 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1865–1878
Lamy PJ, Nanni I, Fina F et al, 2006, Reliability and discriminant validity of HER2 gene amplification and chromosome 17 aneusomy analysis by real-time PCR in primary breast cancer. Int J Biol Markers 21:20–29
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Simon R, Atefy R, Wagner U et al, 2003, HER-2 and TOP2A coamplification in urinary bladder cancer. Int J Cancer 107:764–772
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Gjerdrum LM, Lielpetere I, Rasmussen LM et al, 2001, Laserassisted microdissection of membrane-mounted paraffin sections for polymerase chain reaction analysis: identification of cell populations using immunohistochemistry and in situ hybridization. J Mol Diagn 3:105–110
Persons D, Tubbs R, Cooley LD et al, 2006, HER2 fluorescence in situ hybridization. Arch Pathol Lab Med 130:325–331
Bose S, Mohammed M, Shintaku P et al, 2001, Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy. Breast J 7:337–344
Wang S, Hossein Saboorian M, Frenkel EP et al, 2002, Aneusomy 17 in breast cancer: its role in HER-2/neu protein expression and implication for clinical assessment of HER-2/neu status. Mod Pathol 15:137–145
Gallucci M, Guadagni F, Marzano R et al, 2005, Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9, and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters. J Clin Pathol 58:367–371
Ohta JI, Miyoshi Y, Uemura H et al, 2001, Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer. Clin Cancer Res 7: 2463–2467
Hovey RM, Chu L, Balazs M et al, 1998, Genetic alterations in primary bladder cancers and their metastases. Cancer Res 58:3555–3560
Kelly ED, Yoder BJ, Stoler M et al, 2005, The influence of polysomy 17 on HER2 gene and protein expression in adenocarcinoma of the breast. Am J Surg Pathol 29:1221–1227
Miyamoto H, Kubota Y, Noguchi S et al, 2000, c-erbB-2 gene amplification as a prognostic marker in human bladder cancer. Urology 55:679–683
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 261
EP 266
DI 10.1007/s12253-008-9027-y
PG 6
ER
PT J
AU Lyronis, DI
Baritaki, S
Bizakis, I
Krambovitis, E
Spandidos, AD
AF Lyronis, D Ioannis
Baritaki, Stavroula
Bizakis, Ioannis
Krambovitis, Elias
Spandidos, A Demetrios
TI K-ras Mutation, HPV Infection and Smoking or Alcohol Abuse Positively Correlate with Esophageal Squamous Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Human Papilloma Virus; B-raf; K-ras; N-ras
ID Esophageal squamous cell carcinoma; Human Papilloma Virus; B-raf; K-ras; N-ras
AB The Ras/Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, survival and apoptosis. The aim of this study was to determine the incidence of B-raf, Kirsten-ras (K-ras) and Neuroblastoma-ras (N-ras) gene mutations in esophageal squamous cell carcinoma (ESCC) in the Greek population. DNA was extracted from 30 ESCC and 32 normal esophageal specimens and screened for V600E B-raf, and K-ras/N-ras codon 12 mutations, by PCR-RFLP based analysis. Among the genes tested, only the heterozygous K-ras mutation was detected in 5 out of the 30 ESCC specimens (16%), whereas no mutation was found in the normal esophageal tissue (P<0.022). The normal samples were screened negative for N-ras and V600E B-raf mutations. The increased risk of esophageal cancer was correlated with tobacco use (OR=3.5, P<0.023) and alcohol abuse (OR=7.22, P<0.001), accompanied with the high incidence of the k-ras codon 12 mutation (22%, OR=1.77 and 21%, OR=1.52), respectively. A similar positive association was seen in human papilloma virus (HPV)-infected patients (OR=5.66, P<0.003). Our overall findings demonstrate that the mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for ESCC development.
C1 [Lyronis, D Ioannis] University of Crete, Medical School, Department of Virology, 711 10 Heraklion, Crete, Greece.
[Baritaki, Stavroula] University of Crete, Medical School, Department of Virology, 711 10 Heraklion, Crete, Greece.
[Bizakis, Ioannis] University Hospital of Crete, Department of Otolaryngology, 712 01 Heraklion, Crete, Greece.
[Krambovitis, Elias] University of Thessaly, Department of Veterinary MedicineKarditsa, Greece.
[Spandidos, A Demetrios] University of Crete, Medical School, Department of Virology, 711 10 Heraklion, Crete, Greece.
RP Spandidos, AD (reprint author), University of Crete, Medical School, Department of Virology, 711 10 Heraklion, Greece.
EM spandidos@spandidos.gr
CR Arber N, Shapira I, Ratan J et al, 2000, Activation of c-K-ras mutations in human gastrointestinal tumors. Gastroenterology 118:1045–1050
Arora S, Mathew R, Mathur M et al, 2001, Alterations in MDM2 in esophageal squamous cell carcinoma: relationship with p53 status. Pathol Oncol Res 7:203–208
Bosetti C, Gallus S, Garavello W et al, 2006, Smoking cessation and the risk of oesophageal cancer: an overview of published studies. Oral Oncol 42:957–964
Fenoglio-Preiser CM, 1999, Gastrointestinal pathology. An atlas and text, 2nd edn. Lippincott-Raven, Philadelphia, pp 102–103
Chetty R, Simelane S, 1999, p53 and cyclin A protein expression in squamous carcinoma of the oesophagus. Pathol Oncol Res 5:193–196
Cohen Y, Xing M, Mambo E et al, 2003, BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–627
Davies H, Bignell GR, Cox C et al, 2002, Mutations of the BRAF gene in human cancer. Nature 417:949–954
Ellis A, Field JK, Field EA et al, 1994, Tylosis associated with carcinoma of the oesophagus and oral leukoplakia in a large Liverpool family—a review of six generations. Eur J Cancer B Oral Oncol 30:102–112
Enzinger PC, Mayer RJ, 2003, Esophageal cancer. N Engl J Med 349:2241–2252
Fransen K, Klintenas M, Osterstrom A et al, 2004, Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis 25:527–533
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Lam AK, 2000, Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol 33:71–90
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Lyronis ID, Baritaki S, Bizakis I et al, 2005, Evaluation of the prevalence of human papillomavirus and Epstein–Barr virus in esophageal squamous cell carcinomas. Int J Biol Markers 20:5–10
Mandard AM, Hainaut P, Hollstein M, 2000, Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res 462:335–342
Mercer KE, Pritchard CA, 2003, Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta 1653, 1):25–40, Jun 5
Ramachandran S, Ramadas K, Hariharan R et al, 2006, Single nucleotide polymorphisms of DNA repair genes XRC1 and XPD and its molecular mapping in Indian oral cancer. Oral Oncol 42:350–362
Scully C, Field JK, Tanzawa H, 2000, Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations. Oral Oncol 36:311–327
Sommerer F, Vieth M, Markwarth A et al, 2004, Mutations of BRAF and KRAS2 in the development of Barrett’s adenocarcinoma. Oncogene 23:554–558
Spandidos DA, Sourvinos G, Tsatsanis C et al, 2002, Normal ras genes: their onco-suppressor and pro-apoptotic functions, review). Int J Oncol 21:237–241
Syrjanen KJ, 2002, HPV infections and oesophageal cancer. J Clin Pathol 55:721–728
Talamini G, Capelli P, Zamboni G et al, 2000, Alcohol, smoking and papillomavirus infection as risk factors for esophageal squamous-cell papilloma and esophageal squamous-cell carcinoma in Italy. Int J Cancer 86:874–878
Tavani A, Bertuzzi M, Talamini R et al, 2003, Coffee and tea intake and risk of oral, pharyngeal and esophageal cancer. Oral Oncol 39:695–700
WangWKP, Schwartz M, Malon G et al, 1994, PCR amplification of 40 year-old paraffin-embedded tumour tissues: comparison of four different DNA extraction and purificationmethods. Int J Oncol 5:0–4
Weber A, Langhanki L, Sommerer F et al, 2003, Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22:4757–4759
Wu M, Semba S, Oue N et al, 2004, BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer 7:246–253
Xing M, 2005, BRAF mutation in thyroid cancer. Endocr-Relat Cancer 12:245–262
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 267
EP 273
DI 10.1007/s12253-008-9032-1
PG 7
ER
PT J
AU Szegedi, I
Katona, K
Horvath, A
Molnar, A
Aradi, J
Kiss, Cs
AF Szegedi, Istvan
Katona, Klara
Horvath, Andras
Molnar, Anna
Aradi, Janos
Kiss, Csongor
TI Bcl-2 Antisense Oligonucleotide Inhibits the Proliferation of Childhood Leukemia/lymphoma Cells of the B-cell Lineage
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BCL-2; Antisense oligonucleotide; Childhood; Leukemia; Lymphoma
ID BCL-2; Antisense oligonucleotide; Childhood; Leukemia; Lymphoma
AB An 18-mer phosphorothioate bcl-2 atisense oligonucleotide (ASO) inhibited colony formation of three B-cell leukemia/lymphoma cell lines in a dose dependent manner in the range of 0.125–0.5 μmol/l. The srcambled cogener had no detectable effect. A decrease in BCL-2 protein and apoptotic DNA fragmentation was detected in the studied cell lines and primary blast cells of two children with acute lymphoblastic leukemia. Neither BCL-2 protein level, nor DNA integrity was affected by the scrambled control indicating the specific effect ASO. As far as we know, this is the first report on the effects of bcl-2 ASO on childhood leukemia/lymphoma cell samples.
C1 [Szegedi, Istvan] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98 Nagyerdei Circle, 4012 Debrecen, Hungary.
[Katona, Klara] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Horvath, Andras] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Molnar, Anna] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98 Nagyerdei Circle, 4012 Debrecen, Hungary.
[Aradi, Janos] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98 Nagyerdei Circle, 4012 Debrecen, Hungary.
RP Kiss, Cs (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 4012 Debrecen, Hungary.
EM kisscs@dote.hu
CR Dean NM, Bennett CF, 2003, Antisense oligonucleotide-based therapeutics for cancer. Oncogene 22:9087–9096
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Adis International Limited, 2007, Oblimersen: Augnerosen, Bcl-2 antisense oligonucleitide- Genta, G3139, GC 3139, Oblimersen sodium. Drugs in R&D 5:321–334
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 275
EP 279
DI 10.1007/s12253-008-9076-2
PG 5
ER
PT J
AU Csomor, J
Kaszas, I
Kollar, B
Pajor, L
Egyhazi, Zs
Fekete, S
Egyed, M
Timar, B
AF Csomor, Judit
Kaszas, Ilona
Kollar, Balazs
Pajor, Laszlo
Egyhazi, Zsolt
Fekete, Sandor
Egyed, Miklos
Timar, Botond
TI Prolonged Survival Using Anti-CD20 Combined Chemotherapy in Primary Prostatic Intravascular Large B-cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DLBCL; Intravascular large B-cell lymphoma; Prostate; Rituximab
ID DLBCL; Intravascular large B-cell lymphoma; Prostate; Rituximab
AB Here we report a case of a 73-year-old man with primary intravascular large B-cell lymphoma localized to the prostate. Total prostatectomy was performed due to a benign adenoma suggested by ultrasonography. The diagnosis of IVLBL was obtained incidentally from the prostatectomy specimen. Eight months after the initial R-CHOP chemotherapy a relapse was detected in the left inguinal lymph node, where histologic examination revealed common diffuse large B-cell lymphoma with minimal intravascular component. The second complete remission was achieved by R-IEV therapy. Five months later a second relapse occurred and the patient died in the widespread disease and pneumonia. Primary prostate IVLBL is extremely uncommon; to date only four cases have been described. This is a well documented case, where we also confirmed that the initial primary IVLBL and the secondary lymph node involvement are clonally related. Successful treatment depends on early diagnosis of IVLBL, aggressive chemotherapy and the fact that IVLBL should be considered as a generalized disease in spite of negative staging results.
C1 [Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Kaszas, Ilona] Szt. Margit Hospital, Department of PathologyBudapest, Hungary.
[Kollar, Balazs] Kaposi Mor Teaching Hospital, Department of OncohematologyKaposvar, Hungary.
[Pajor, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Egyhazi, Zsolt] Kaposi Mor Teaching Hospital, Department of OncohematologyKaposvar, Hungary.
[Fekete, Sandor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Egyed, Miklos] Kaposi Mor Teaching Hospital, Department of OncohematologyKaposvar, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Csomor, J (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM csomor@korb1.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 281
EP 284
DI 10.1007/s12253-008-9051-y
PG 4
ER
PT J
AU Markasz, L
Hajas, Gy
Kiss, A
Lontay, B
Rajnavolgyi,
Erdodi, F
Olah,
AF Markasz, Laszlo
Hajas, Gyorgy
Kiss, Andrea
Lontay, Beata
Rajnavolgyi, Eva
Erdodi, Ferenc
Olah, Eva
TI Granulocyte Colony Stimulating Factor Increases Drug Resistance of Leukaemic Blast Cells to Daunorubicin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute leukaemia; Daunorubicin; Drug sensitivity; G-CSF; G-CSF-R
ID Acute leukaemia; Daunorubicin; Drug sensitivity; G-CSF; G-CSF-R
AB Acute leukaemia is known as the most common cancer in childhood. Febrile neutropenia is a common serious side effect of the cytostatic treatment of malignancies. The clinical use of Granulocyte Colony Stimulating Factor (G-CSF) has become widespread to minimize chemotherapy-induced myelosuppression and febrile neutropenia in childhood solid tumors, acute lymphoid leukaemia (ALL) and in several trials with AML. In case of ALL this seems to be reasonable because, due to the absence of G-CSF receptor (G-CSFR) on the surface of normal lymphoid cells, G-CSF does not have any influence on the pathways of proliferation and differentiation of lymphoid lineage cells. It has been suggested, however, that ALL blasts with B or T cell surface antigens as well as biphenotypic leukaemia cells express G-CSFR, and they are able to respond to exogenously added G-CSF with proliferation. In this study we investigated how G-CSF might influence the sensitivity of leukemic cells to daunorubicin induced cell death using MTT assay, flow cytometry and Western blot analysis. After pretreatment of KG-1 leukaemic cells with G-CSF a moderate increase in the resistance of these cells to daunorubicin could be observed. These results draw attention to the risk of G-CSF application as an adjuvant therapy of childhood ALL. In addition, adjuvant treatment of AML patients with G-CSF in order to prevent neutropenia, or its use in priming regimens might result resistance to daunorubicin.
C1 [Markasz, Laszlo] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hajas, Gyorgy] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kiss, Andrea] University of Debrecen, Faculty of Medicine, Department of Medical Chemistry, Egyetem ter 1, 4032 Debrecen, Hungary.
[Lontay, Beata] University of Debrecen, Faculty of Medicine, Department of Medical Chemistry, Egyetem ter 1, 4032 Debrecen, Hungary.
[Rajnavolgyi, Eva] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Erdodi, Ferenc] University of Debrecen, Faculty of Medicine, Department of Medical Chemistry, Egyetem ter 1, 4032 Debrecen, Hungary.
[Olah, Eva] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Olah, (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 4032 Debrecen, Hungary.
EM markaszl@freemail.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 285
EP 292
DI 10.1007/s12253-008-9057-5
PG 8
ER
PT J
AU Matusan-Ilijas, K
Behrem, S
Jonjic, N
Zarkovic, K
Lucin, K
AF Matusan-Ilijas, Koviljka
Behrem, Senija
Jonjic, Nives
Zarkovic, Kamelija
Lucin, Ksenija
TI Osteopontin Expression Correlates with Angiogenesis and Survival in Malignant Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Immunohistochemistry; Osteopontin; Pathological angiogenesis; Prognosis
ID Glioma; Immunohistochemistry; Osteopontin; Pathological angiogenesis; Prognosis
AB Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including angiogenesis, cancer development, invasion and metastasis. The aim of the study was to analyze the expression of OPN in human astrocytomas and to correlate it with angiogenesis and patients’ outcome. Seventy-six human astrocytomas including eight pilocytic astrocytomas (grade I), 10 diffuse astrocytomas (grade II), 8 anaplastic astrocytomas (grade III) and 50 glioblastomas (grade IV) were immunohistochemically stained for OPN protein. The distribution of OPN staining (cytoplasmic and/or interstitial)was assessed and compared tomicrovessel number and patients’ survival. In normal brain tissue some glial and neuronal cells showed weak cytoplasmic staining, while interstitium was negative. Astrocytomas were heterogeneous regarding the OPN expression. High cytoplasmic OPN expression in glioblastomas was associated with poor patients’ survival (p=0.012). Also, we found the association of interstitial OPN expression and angiogenesis (p=0.033), i.e. the number of newly formed blood vessels was higher in tumors showing high interstitial OPN expression. Our results indicate the overexpression of OPN protein in astrocytoma cells and suggest the role of OPN in astrocytoma progression and angiogenesis.
C1 [Matusan-Ilijas, Koviljka] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
[Behrem, Senija] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
[Jonjic, Nives] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
[Zarkovic, Kamelija] University Hospital Center Zagreb, Department of Pathology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Lucin, Ksenija] Rijeka University School of Medicine, Department of Pathology, Brace Branchetta 20, 51 000 Rijeka, Croatia.
RP Matusan-Ilijas, K (reprint author), Rijeka University School of Medicine, Department of Pathology, 51 000 Rijeka, Croatia.
EM kmatusan@yahoo.com
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Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds,, 2007, WHO classification of tumours of the central nervous system, fourth edition. IARC Press, Lyon
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Saitoh Y, Kuratsu J, Takeshima H et al, 1995, Expression of osteopontin in human glioma. Its correlation with the malignancy. Lab Invest 72:55–63
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Jang T, Savarese T, Low HP et al, 2006, Osteopontin expression in intratumoural astrocytes marks tumour progression in gliomas induced by prenatal exposure to N-ethyl-N-nitrosourea. Am J Pathol 168:1676–1685
Tucker MA, Chang PL, Prince CW et al, 1998, TPA-mediated regulation of osteopontin in human malignant glioma cells. Anticancer Res 18:807–812
Colin C, Baeza N, Bartoli C et al, 2006, Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using suppression subtractive hybridization. Oncogene 25:2818–2826
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 293
EP 298
DI 10.1007/s12253-008-9058-4
PG 6
ER
PT J
AU Orban, E
Szabo, E
Lotz, G
Kupcsulik, P
Paska, Cs
Schaff, Zs
Kiss, A
AF Orban, Erika
Szabo, Erzsebet
Lotz, Gabor
Kupcsulik, Peter
Paska, Csilla
Schaff, Zsuzsa
Kiss, Andras
TI Different Expression of Occludin and ZO-1 in Primary and Metastatic Liver Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Colorectal liver metastasis; Occludin; ZO-1
ID Hepatocellular carcinoma; Colorectal liver metastasis; Occludin; ZO-1
AB Tight junction (TJ) components were found to be correlated with carcinogenesis and tumor development. TJs are composed of three main integral membrane proteins; occludin, claudins and JAMs. Alteration of the TJ protein expression may play an important role in the process of cell dissociation, which is among the first steps of tumor invasion and metastasis. Reduced expression of ZO-1 has been reported to be associated with invasion of several tumors. The aim of the present study was to detect differences between occludin and ZO-1 expression in normal liver samples, HCCs and colorectal liver metastases. Expression of occludin and ZO-1 was analysed in 25 surgically removed human hepatocellular carcinomas (HCC) and 25 human colorectal liver metastases. Gene expression levels were measured by real-time RT PCR, protein expression was determined by immunohistochemistry, comparing tumors with the surrounding nontumorous parenchyma and with seven normal liver samples. Occludin and ZO-1 mRNAs showed significant downregulation in HCCs in comparison with normal liver and were also downregulated in the metastases when compared with normal liver. Occludin and ZO-1 proteins were weakly expressed on hepatocytes in normal liver, while strong expression was found on bile canaliculi. In HCCs occludin and ZO-1 did not show immunopositivity on tumor cells, while colorectal metastatic tumors revealed high levels of these molecules. HCCs and metastases are characterized by markedly different protein expression pattern of occludin and ZO-1, which phenomenon might be attributed to the different histogenesis of these tumors.
C1 [Orban, Erika] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Szabo, Erzsebet] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Kupcsulik, Peter] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Paska, Csilla] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Jiang WG, 1998, Cell adhesion molecules in the formation of liver metastasis. J Hepatobiliary Pancreat Surg 5:375–382
Kaihara T, Kusaka T, Nishi M et al., 2003, Dedifferentiation and decreased expression of adhesion molecules, E-cadherin and ZO-1, in colorectal cancer are closely related to liver metastasis. J Exp Clin Cancer Res 22:117–123
Sakisaka S, Kawaguchi T, Taniguchi E et al., 2001, Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 33:1460–1468
Kojima T, Yamamoto T, Murata M et al., 2003, Regulation of the blood–biliary barrier: interaction between gap and tight junctions in hepatocytes. Med Electron Microsc 36:157–164
Haynes MD, Martin TA, Jenkins SA et al., 2005, Tight junctions and bladder cancer, review). Int J Mol Med 16:3–9
Cereijido M, Shoshani L, Contreras RG, 2000, Molecular physiology and pathophysiology of tight junctions. I. Biogenesis of tight junctions and epithelial polarity. Am J Physiol Gastrointest Liver Physiol 279:G477–482
Fanning AS, Mitic LL, Anderson JM, 1999, Transmembrane proteins in the tight junction barrier. J Am SocNephrol 10:1337–1345
Saitou M, Furuse M, Sasaki H et al., 2000, Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142
Gonzalez-Mariscal L, Betanzos A, Nava P et al., 2003, Tight junction proteins. Prog Biophys Mol Biol 81:1–44
Itoh M, Nagafuchi A, Yonemura S et al., 1993, The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J Cell Biol 121:491–502
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Ebnet K, Schulz CU, Meyer Zu Brickwedde MK et al., 2000, Junctional adhesion molecule interacts with the PDZ domaincontaining proteins AF-6 and ZO-1. J Biol Chem 275:27979– 27988
Fanning AS, Jameson BJ, Jesaitis LA et al., 1998, The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273:29745–29753
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Fanning AS, Anderson JM, 1999, PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane. J Clin Invest 103:767–772
Lodi C, Szabo E, Holczbauer A et al., 2006, Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas. Mod Pathol 19:460–469
Pfaffl MW, Horgan GW, Dempfle L, 2002, Relative expression software tool, REST, for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36
Tan X, Tamori Y, Egami H et al., 2004, Analysis of invasionmetastasis mechanism in pancreatic cancer: involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation. Oncol Rep 11:993–998
Schneeberger EE, Lynch RD, 2004, The tight junction: a multifunctional complex. Am J Physiol Cell Physiol 286: C1213–1228
Saitou M, Fujimoto K, Doi Y et al., 1998, Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J Cell Biol 141:397– 408
Smalley KS, Brafford P, Haass NK et al., 2005, Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am J Pathol 166:1541–1554
Mauro L, Bartucci M, Morelli C et al., 2001, IGF-I receptorinduced cell–cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1. J Biol Chem 276:39892– 39897
Palmer HG, Gonzalez-Sancho JM, Espada J et al., 2001, Vitamin D(3, promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol 154:369–387
Brabletz T, Jung A, Reu S et al., 2001, Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A 98:10356–10361
Busch C, Hanssen TA, Wagener C et al., 2002, Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition. Hum Pathol 33:290–298
Kimura Y, Shiozaki H, Hirao M et al., 1997, Expression of occludin, tight-junction-associated protein, in human digestive tract. Am J Pathol 151:45–54
Soini Y, 2005, Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology. 46:551–60
Cheung ST, Leung KL, Ip YC et al., 2005, Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res 11:551–556
Ishikawa Y, Akishima-Fukasawa Y, Ito K et al., 2008, Histopathologic determinants of regional lymph node metastasis in early colorectal cancer. Cancer 112:924–933
Kominsky SL, Tyler B, Sosnowski J et al., 2007, Clostridium perfringens enterotoxin as a novel-targeted therapeutic for brain metastasis. Cancer Res 67:7977–7982
Sawada N, Murata M, Kikuchi K et al., 2003, Tight junctions and human diseases. Med Electron Microsc 36:147–156
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 299
EP 306
DI 10.1007/s12253-008-9031-2
PG 8
ER
PT J
AU Romics, I
Banfi, G
Szekely, E
Krenacs, T
Szende, B
AF Romics, Imre
Banfi, Gergely
Szekely, Eszter
Krenacs, Tibor
Szende, Bela
TI Expression of p21waf1/cip1, p27kip1, p63 and Androgen Receptor in Low and High Gleason Score Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE High Gleason score; Loss of p27kip1; Prostate adenocarcinoma
ID High Gleason score; Loss of p27kip1; Prostate adenocarcinoma
AB The aim of this study was to investigate the expression of p21waf1/cip1, p27kip1, p63 and androgen receptor proteins in relation to serum prostate specific antigen levels in low and high Gleason score prostate cancers. Biopsies of patients suffering from prostate adenocarcinoma of low (3+3 to 3+4) and high (5+4 to 5+5) Gleason scores (13 cases each group) were immunostained for positive regulators of cell cycle control (p21waf1/cip1 and p27kip1), and essential markers of normal prostate gland ontogeny (p63) and growth (androgen receptor) to find differentially expressed markers of malignant progression. Serum prostate specific antigen levels were also monitored at the time of biopsy and following anti-androgen therapy. All cases except one in each group were androgen receptor positive. P63 and p21waf1/cip1 proteins detected in normal basal cell nuclei were lost in all but one studied tumors respectively. P27kip1 protein, however, was detected in all low Gleason score prostate cancers, but it was found in only 7/13 high score cases. Prostate specific antigen levels, either pre- or post-treatment, did not show strict correlation with the p27kip1 results. The low to high grade dedifferentiation of prostate adenocarcinoma is accompanied with the downregulation of p27kip1 protein, which may be an important molecular sign of the lost cell cycle control.
C1 [Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
[Banfi, Gergely] Semmelweis University, Department of UrologyBudapest, Hungary.
[Szekely, Eszter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Krenacs, Tibor] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi u. 26, 1085 Budapest, Hungary.
[Szende, Bela] Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, Ulloi u. 26, 1085 Budapest, Hungary.
RP Szende, B (reprint author), Hungarian Academy of Sciences and Semmelweis University, Research Group of Molecular Pathology, 1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Isaacs JT, Lundmo PI, Berges R, Martikainen P, Kyprianou N, English HF, 1992, Androgen regulation of programmed death of normal and malignant prostatic cells. J Androl 13:457–464
Eder IE, Culig Z, Putz T, Nessler-Menardi C, Bartsch G, Klocker H, 2001, Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur Urol 40:241–251
Stamey TA, Warrington JA, Caldwell MC et al, 2001, Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia. J Urol 166:2171–2177
Porkka KP, Visakorpi T, 2001, Detection of differentially expressed genes in prostate cancer by combining suppression subtractive hybridization and cDNA library assay. J Pathol 193:73–79
Meehan KL, Holland JW, Dawkins HJ, 2002, Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer. Prostate 50:54–63
Baretton GB, Klenk U, Diebold J, Schmeller N, Lohrs U, 1999, Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression. Br J Cancer 80:546–555
Eder IE, Bektic J, Haag P, Bartsch G, Klocker H, 2004, Genes differentially expressed in prostate cancer. BJU Int 93:1151–1155
Szende B, Romics I, Minik K, Szabo J, Torda I, Lovasz S, Toth L, Bely M, Kerenyi T, Bartok K, Vegh A, 2001, Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma. Prostate 49:93–100
Waltregny D, Leav I, Signoretti S, Soung P, Lin D, Merk F, Adams JY, Bhattecharya N, Cirenei N, Loda M, 2001, Androgendriven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27. Mol Endocrinol 15:765–782
Koffer L, Roshong S, Park IK, Cesen-Cummings K, Thopson DR, Dwyer-Nield LD, Rice P, Mamay C, Malkinson AM, Ruch RJ, 2000, Growth inhibition in G1 and altered expression of cyclin D1 and p27kip1 after forced connexin expression in lung and liver carcinoma cells. J Cell Biochem 79:347–354
Zhang Y-W, Morite I, Ikeda M, Ma K-W, Murota S, 2001, Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post-transcriptional regulation of p27. Oncogene 20:4138–4149
Gorbe A, Becker DL, Dux L, Stelkovics E, Krenacs L, Bagdi E, Krenacs T, 2005, Transient upregulation of connenxin43 gap junctions and synchronized cell cycle control precede myoblast fusion in regenerating skeletal muscle in vivo. Histochem Cell Biol 123:573–583
Lawlor MA, Rotwein P, 2000, Coordinate control of muscle cell survival by distinct insulin-like growth factor activated signaling pathways. J Cell Biol 151:1131–1140
Ostrovsky O, Bengal E, 2003, The mitogen-activated protein kinase cascade promotes myoblast cell survival by stabilizing the cyclin-dependent kinase inhibitor, p21WAF1 protein. J Biol Chem 278:21221–21231
Fizazi K, Martizez LA, Sikes CR, Johnston DA, Stephens LC, McDonnell TJ, Logothetis CJ, Trapman J, Pisters LL, Ordonez NG, Troncoso P, Navone NM, 2002, The association of p21, WAF- 1/CIP1, with progression to androgen-independent prostate cancer. Clin Cancer Res 8:775–781
Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M, 2000, P63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157:1769–1775
Ronison IB, 2003, Tumor cell senescence in cancer treatment. Cancer Res 63:2705–2715
Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C, 2002, P63 expression profiles in human normal and tumor tissues. Clin Can Res 8:494–501
Cordon-Cardo G, Koff A, Drobnjak M, Caodieci P, Osman I, Millard SS, 1998, Distinct altered patterns of 27kip1 gene expression in benign prostate hyperplasia and prostatic carcinoma. J Natl Cancer Inst 90:1284–1291
Guo Y, Sklar GN, Borkowski A, Kyprianou N, 1997, Loss of the cyclin dependent kinase inhibitor p27(Kip1, protein in human prostate cancers correlates with tumor grade. Clin Cancer Res 3:2269–2274
Kuczyk M, Machtens S, Hradil K et al, 1999, Predictive value of p27Kip1 protein expression for the recurrence-free and longterm survival of prostate cancer patients. Br J Cancer 81:1052– 1058
Doganavsargil B, Simsir A, Boyacioglu H, Cal C, Hekimgil M, 2006, A comparison of p21 and p27 immunoexpression in benign glands, prostatic intraepithelial neoplasia and prostate adenocarcinoma. BJU Int 97:644–648
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 307
EP 311
DI 10.1007/s12253-008-9042-z
PG 5
ER
PT J
AU Mark, Zs
Bajzik, G
Nagy, A
Bogner, P
Repa, I
Strausz, J
AF Mark, Zsuzsa
Bajzik, Gabor
Nagy, Andrea
Bogner, Peter
Repa, Imre
Strausz, Janos
TI Comparison of Virtual and Fiberoptic Bronchoscopy in the Management of Airway Stenosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bronchoscopy; Computed tomography; Interventional bronchoscopy .Virtual bronchoscopy
ID Bronchoscopy; Computed tomography; Interventional bronchoscopy .Virtual bronchoscopy
AB Noninvasive imaging methods can be valuable tools for diagnosing thoracic diseases, especially malignancies. The aim of this study was to compare the effectiveness of conventional and virtual bronchoscopy in the follow-up of patients with large airway stenosis. Twenty-three consecutive patients with stenoses of the trachea and/or the main bronchi were enrolled in this prospective observer study. The causes of stenosis included malignant or benign tumours, goiter, and postintubation stenoses. Patients were evaluated before and after treatment (which included mechanical dilation, laser photocoagulation, stent implantation, radiotherapy, chemotherapy, and surgical resection). The mean time between baseline and follow-up endoscopy was 140 days. No significant differences were observed between the estimated and measured data from bronchofibroscopy and virtual bronchoscopy. Exact measurement of stenoses was performed with virtual bronchoscopy.
C1 [Mark, Zsuzsa] Pest County Hospital, III.Pulmonology, Munkacsy Mihaly 70, 2045 Torokbalint, Hungary.
[Bajzik, Gabor] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Nagy, Andrea] Pest County Hospital, III.Pulmonology, Munkacsy Mihaly 70, 2045 Torokbalint, Hungary.
[Bogner, Peter] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Repa, Imre] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Strausz, Janos] National Koranyi Institute of Pulmonology, Piheno u. 1, 1125 Budapest, Hungary.
RP Mark, Zs (reprint author), Pest County Hospital, III.Pulmonology, 2045 Torokbalint, Hungary.
EM markzs@t-online.hu
CR Neumann K, Winterer J, Kimmig M et al, 2000, Real-time interactive virtual endoscopy of the tracheo-bronchial system: influence of CT imaging protocols and observer ability. Eur J Radiol 33:50–54
Hoppe H, Walder B, Sonnenschein M et al, 2002, Multidetector CT virtual bronchoscopy to grade tracheobronchial stenosis. AJR Am J Roentgenol 178:1195–1200
Liewald F, Lang G, Fleiter T et al, 1998, Comparison of virtual and fiberoptic bronchoscopy. Thorac Cardiovasc Surg 46:361–364
Mark Zs, Bajzik G, Repa I et al, 2001, Virtual bronchoscopy: a new non-invasive diagnostic method in pulmonology. Orv Hetil 142:565–569
Haponik EF, Aquino SL, Vining DJ, 1999, Virtual bronchoscopy. Clin Chest Med 20:201–217
Heyer CM, Nuesslein TG, Jung D et al, 2007, Tracheobronchial anomalies and stenoses: detection with low-dose multidetector CT with virtual tracheobronchoscopy—comparison with flexible tracheabronchoscopy. Radiology 242:542–549
Burke AJ, Vining DJ, McGuirt WF et al, 2000, Evaluation of airway obstruction using virtual endoscopy. Laryngoscope 110:23–29
Colt HG, Crawford SW, Galbraith O III, 2001, Virtual reality bronchoscopy simulation: a revolution in procedural training. Chest 120:1333–1339
McAdams HP, Goodman PC, Kussin P, 1998, Virtual bronchoscopy for directing transbronchial needle aspiration of hilar and mediastinal lymph nodes: a pilot study. AJR Am J Roentgenol 170:1361–1364
Summers RM, 1997, Navigational aids for real-time virtual bronchoscopy. AJR Am J Roentgenol 168:1165–1170
Ferretti G, 1999, Virtual endoscopy: which indications? Rev Mal Respir 3:59–60
Bauer TL, Steiner KV, 2007, Virtual bronchoscopy: clinical applications and limitations. Surg Oncol Clin N Am 16:323– 328
Summers RM, Shaw DJ, Shelhamer JH, 1998, CT virtual bronchoscopy of simulated endobronchial lesions: effect of scanning, reconstruction, and display settings and potential pitfalls. AJR Am J Roentgenol 170:947–950
Koletsis EN, Kalogeropoulu C, Prodromaki E et al, 2007, Tumoral and non-tumoral trachea stenoses: evaluation with three dimensional CT and virtual bronchoscopy. J Cardiothorac Surg 2:18
Amorico MG, Drago A, Vetruccio E et al, 2006, Tracheobronchial stenosis: role of virtual endoscopy in diagnosis and follow-up after therapy. Radiol Med, Torino, 111:1064–1077
Ferretti GR, Kocier M, Calaque O et al, 2003, Follow-up after stent insertion in the tracheobronchial tree: role of helical computed tomography in comparison with fiberoptic bronchoscopy. Eur Radiol 13:1172–1178
Mark Zs, Bajzik G, Nagy A et al, 2004, Virtual bronchoscopy for follow-up investigation of main airway stenoses. Orv Hetil 145:1233–1235
Shitrit D, Valdsislav P, Grubstein A et al, 2005, Accuracy of virtual bronchoscopy for grading tracheobronchial stenosis: correlation with pulmonary function test and fiberoptic bronchoscopy. Chest 128:3545–3550
Finkelstein SE, Schrump DS, Nguyen DM et al, 2003, Comparative evaluation of super high-resolution CT scan and virtual bronchoscopy for the detection of tracheobronchial malignancies. Chest 124:1834–1840
Higgins WE, Ramaswamy K, Swift RD et al, 1998, Virtual bronchoscopy for three-dimensional pulmonary image assessment: state of the art and future needs. Radiographics 18:761–778
Wood BJ, Razavi P, 2002, Virtual endoscopy: a promising new technology. Am Fam Physician 66:107–112
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 313
EP 319
DI 10.1007/s12253-008-9059-3
PG 7
ER
PT J
AU Hussein, RM
Fathi, AN
El-Din, MEA
Hassan, IH
Abdullah, F
AL-Hakeem, E
Backer, AE
AF Hussein, R Mahmoud
Fathi, A Nehal
El-Din, M Ezz Azza
Hassan, I Hewayda
Abdullah, Fatemah
AL-Hakeem, Eman
Backer, Abo Eman
TI Alterations of the CD4+, CD8+ T Cell Subsets, Interleukins-1β, IL-10, IL-17, Tumor Necrosis Factor-α and Soluble Intercellular Adhesion Molecule-1 in Rheumatoid Arthritis and Osteoarthritis: Preliminary Observations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rheumatoid arthritis; Osteoarthritis; Tcells
ID Rheumatoid arthritis; Osteoarthritis; Tcells
AB Rheumatoid arthritis is a multisystem disease with underlying immune mechanisms. Osteoarthritis is a debilitating, progressive disease of diarthrodial joints associated with the aging process. Although much is known about the pathogenesis of rheumatoid arthritis and osteoarthritis, our understanding of some immunologic changes remains incomplete. This study tries to examine the numeric changes in the T cell subsets and the alterations in the levels of some cytokines and adhesion molecules in these lesions. To accomplish this goal, peripheral blood and synovial fluid samples were obtained from 24 patients with rheumatoid arthritis, 15 patients with osteoarthritis and six healthy controls. The counts of CD4 + and CD8 + T lymphocytes were examined using flow cytometry. The levels of some cytokines (TNF-α, IL1-β, IL-10, and IL-17) and a soluble intercellular adhesion molecule-1 (sICAM-1) were measured in the sera and synovial fluids using enzyme linked immunosorbant assay. We found some variations in the counts of T cell subsets, the levels of cytokines and sICAM-1 adhesion molecule between the healthy controls and the patients with arthritis. High levels of IL-1β, IL-10, IL-17 and TNF-α (in the serum and synovial fluid) were observed in arthritis compared to the healthy controls. In rheumatoid arthritis, a high serum level of sICAM-1 was found compared to its level in the synovial fluid. A high CD4+/CD8+ T cell ratio was found in the blood of the patients with rheumatoid arthritis. In rheumatoid arthritis, the cytokine levels correlated positively with some clinicopathologic features. To conclude, the development of rheumatoid arthritis and osteoarthritis is associated with alteration of the levels of some cytokines. The assessment of these immunologic changes may have potential prognostic roles.
C1 [Hussein, R Mahmoud] Assuit University, Assuit University Hospitals, Department of PathologyAssuit, Egypt.
[Fathi, A Nehal] Assuit and Ein Shams Universities, Faculty of Medicine, Assuit University Hospitals, Departments of Rheumatology and RehabilitationAssuit, Egypt.
[El-Din, M Ezz Azza] Assuit University, Assuit University Hospitals, Department of PathologyAssuit, Egypt.
[Hassan, I Hewayda] Assuit University, Assuit University Hospitals, Department of PathologyAssuit, Egypt.
[Abdullah, Fatemah] Assuit and Ein Shams Universities, Faculty of Medicine, Assuit University Hospitals, Departments of Rheumatology and RehabilitationAssuit, Egypt.
[AL-Hakeem, Eman] Assuit and Ein Shams Universities, Faculty of Medicine, Assuit University Hospitals, Departments of Rheumatology and RehabilitationAssuit, Egypt.
[Backer, Abo Eman] Assuit and Ein Shams Universities, Faculty of Medicine, Assuit University Hospitals, Departments of Rheumatology and RehabilitationAssuit, Egypt.
RP Hussein, RM (reprint author), Assuit University, Assuit University Hospitals, Department of Pathology, Assuit, Egypt.
EM mrcpath17@gmail.com
CR Maurer D, Felzmann T, Holter W, Petera P, Smolen J, Knapp W, 1992, Evidence for the presence of activated CD4 T cells with naive phenotype in the peripheral blood of patients with rheumatoid arthritis. Clin Exp Immunol 87:429–434
Frye CA, Yocum DE, Tuan R, Suyana E, Seftor EA, Seftor RE, Khalkhali-Ellis Z, Moore TL, Hendrix MJ, 1996, An in vitro model for studying mechanisms underlying synoviocyte-mediated cartilage invasion in rheumatoid arthritis. Pathol Oncol Res 2:157–166
Khalkhali-Ellis Z, Bulla GA, Schlesinger LS, Kirschmann DA, Moore TL, Hendrix MJ, 1999, C1q-containing immune complexes purified from sera of juvenile rheumatoid arthritis patients mediate IL-8 production by human synoviocytes: role of C1q receptors. J Immunol 163:4612–4620
Choy EH, Connolly DJ, Rapson N, Jeal S, Brown JC, Kingsley GH, Panayi GS, Johnston JM, 2000, Pharmacokinetic, pharmacodynamic and clinical effects of a humanized IgG1 anti-CD4 monoclonal antibody in the peripheral blood and synovial fluid of rheumatoid arthritis patients. Rheumatology, Oxford, 39:1139– 1146
Khalkhali-Ellis Z, Roodman ST, Knutsen AP, Mueller KR, Chauhan B, Moore TL, Hendrix MJ, 1998, Expression of macrophage markers by a population of T cells obtained from synovial fluid of a subgroup of patients with juvenile rheumatoid arthritis. J Rheumatol 25:352–360
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T, 1999, IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103:1345–1352
Zwerina J, Redlich K, Schett G, Smolen JS, 2005, Pathogenesis of rheumatoid arthritis: targeting cytokines. Ann N Y Acad Sci 1051:716–729
Malemud CJ, 2004, Cytokines as therapeutic targets for osteoarthritis. BioDrugs 18:23–35
Aigner T, Sachse A, Gebhard PM, Roach HI, 2006, Osteoarthritis: pathobiology-targets and ways for therapeutic intervention. Adv Drug Deliv Rev 58:128–149
Zangerle PF, De Groote D, Lopez M, Meuleman RJ, Vrindts Y, Fauchet F, Dehart I, Jadoul M, Radoux D, Franchimont P, 1992, Direct stimulation of cytokines, IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF, in whole blood: II. Application to rheumatoid arthritis and osteoarthritis. Cytokine 4:568–575
Ezawa K, Yamamura M, Matsui H, Ota Z, Makino H, 1997, Comparative analysis of CD45RA- and CD45RO-positive CD4 + T cells in peripheral blood, synovial fluid, and synovial tissue in patients with rheumatoid arthritis and osteoarthritis. Acta Med Okayama 51:25–31
Petrovic-Rackov L, Pejnovic N, 2005, Clinical significance of IL- 18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis. Clin Rheumatol 25:448–452
Firestein GS, 2005, Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. J Clin Rheumatol 11(3 Suppl):S39–44
Abramson SB, Amin A, 2002, Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology, Oxford, 41:972–980
Attur MG, Patel IR, Patel RN, Abramson SB, Amin AR, 1998, Autocrine production of IL-1 beta by human osteoarthritisaffected cartilage and differential regulation of endogenous nitric oxide, IL-6, prostaglandin E2, and IL-8. Proc Assoc Am Physicians 110:65–72
Appel H, Neure L, Kuhne M, Braun J, Rudwaleit M, Sieper J, 2004, An elevated level of IL-10- and TGFbeta-secreting T cells, B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis. Clin Rheumatol 23:435–440
Verhoef CM, van Roon JA, Vianen ME, Bijlsma JW, Lafeber FP, 2001, Interleukin 10, IL-10), not IL-4 or interferon-gamma production, correlates with progression of joint destruction in rheumatoid arthritis. J Rheumatol 28:1960–1966
Miossec P, 2004, IL-17 in rheumatoid arthritis: a new target for treatment or just another cytokine? Joint Bone Spine 71:87–90
Ryu S, Lee JH, Kim SI, 2006, IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes. Clin Rheumatol 25:16–20
Lindsley HB, Smith DD, Davis LS, Koch AE, Lipsky PE, 1992, Regulation of the expression of adhesion molecules by human synoviocytes. Semin Arthritis Rheum 21:330–334
Cush JJ, Rothlein R, Lindsley HB, Mainolfi EA, Lipsky PE, 1993, Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis. Arthritis Rheum 36:1098–1102
Gonzalez-Gay MA, Garcia-Unzueta MT, De Matias JM, Gonzalez- Juanatey C, Garcia-Porrua C, Sanchez-Andrade A, Martin J, Llorca J, 2006, Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis. Clin Exp Rheumatol 24:373–379
Albert DA, Huang G, Dubrow G, Brensinger CM, Berlin JA, Williams HJ, 2004, Criteria for improvement in rheumatoid arthritis: alternatives to the American College of Rheumatology 20. J Rheumatol 31(5):856–866
Hussein MR, Hassan HI, Hofny ER, Elkholy M, Fatehy NA, Abd Elmoniem AE, Ezz El-Din AM, Afifi OA, Rashed HG, 2005, Alterations of mononuclear inflammatory cells, CD4/CD8 + T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis. J Clin Pathol 58:178–184
Barrera P, Faure S, Prud’homme JF, Balsa A, Migliorini P, Chimenti D, Radstake TR, van de Putte LB, Pascual-Salcedo D, Westhovens R, Maenaut K, Alves H, Lopes-Vaz A, Stravopoulos C, Spyropoulou M, Fritz P, Bardin T, Charron D, Lepage V, Alibert, Martinez M, Cornelis F, 2001, European genetic study on rheumatoid arthritis: is there a linkage of the interleukin-1, IL-1), IL-10 or IL-4 genes to RA? Clin Exp Rheumatol 19:709–714
Chabaud M, Page G, Miossec P, 2001, Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein- 3alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines. J Immunol 167:6015–6020
Petrovic-Rackov L, 2006, Evaluation of the degree of clinical rheumatoid arthritis activity based on the concentrations of cytokines TNF-alpha, IL-12, IL-15, and IL-18 in serum and synovial fluid]. Vojnosanit Pregl 63:21–26
Brennan FM, Hayes AL, Ciesielski CJ, Green P, Foxwell BM, Feldmann M, 2002, Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid arthritis. Arthritis Rheum 46:31–41
Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S, Blanchard D, Gaillard C, Das Mahapatra B, Rouvier E, Golstein P, Banchereau J, Lebecque S, 1998, T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183:2593–2603
Chabaud M, Fossiez F, Taupin JL, Miossec P, 1998, Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 161:409–414
Khalkhali-Ellis Z, Seftor EA, Nieva DR, Seftor RE, Samaha HA, Bultman L, De Larco JE, Ince A, Moore TL, Hendrix MJ, 1997, Induction of invasive and degradative phenotype in normal synovial fibroblasts exposed to synovial fluid from patients with juvenile rheumatoid arthritis: role of mononuclear cell population. J Rheumatol 24:2451–2460
Cush JJ, Splawski JB, Thomas R, McFarlin JE, Schulze-Koops H, Davis LS, Fujita K, Lipsky PE, 1995, Elevated interleukin-10 levels in patients with rheumatoid arthritis. Arthritis Rheum 38:96–104
Macchioni P, Boiardi L, Casali B, Nicoli D, Farnetti E, Salvarani C, 2000, Intercellular adhesion molecule 1, ICAM-1, gene polymorphisms in Italian patients with rheumatoid arthritis. Clin Exp Rheumatol 18:553–558
Blann AD, Herrick A, Jayson MI, 1995, Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis. Br J Rheumatol 34:814–819
Dolezalova P, Telekesova P, Nemcova D, Hoza J, 2002, Soluble adhesion molecules ICAM-1 and E-selectin in juvenile arthritis: clinical and laboratory correlations. Clin Exp Rheumatol 20: 249–254
Hanyuda M, Kasama T, Isozaki T, Matsunawa MM, Yajima N, Miyaoka H, Uchida H, Kameoka Y, Ide H, Adachi M, 2003, Activated leucocytes express and secrete macrophage inflammatory protein-1alpha upon interaction with synovial fibroblasts of rheumatoid arthritis via a beta2-integrin/ICAM-1 mechanism. Rheumatology, Oxford, 42:1390–1397
Pigott R, Dillon LP, Hemingway IH, Gearing AJ, 1992, Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 187:584–589
Lindsley HB, Smith DD, Cohick CB, Koch AE, Davis LS, 1993, Proinflammatory cytokines enhance human synoviocyte expression of functional intercellular adhesion molecule-1, ICAM-1). Clin Immunol Immunopathol 68:311–320
Fitzgerald JE, Ricalton NS, Meyer AC, West SG, Kaplan H, Behrendt C, Kotzin BL, 1995, Analysis of clonal CD8 + T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol 154:3538–3547
Burmester GR, Stuhlmuller B, Keyszer G, Kinne RW, 1997, Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in arthritis? Arthritis Rheum 40:5–18
Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B, 2005, Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 64:1263–1267
Miltenburg AM, van Laar JM, de Kuiper R, Daha MR, Breedveld FC, 1992, T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset. Scand J Immunol 35:603–610
Rittner HL, Zettl A, Jendro MC, Bartz-Bazzanella P, Goronzy JJ, Weyand CM, 1997, Multiple mechanisms support oligoclonal T cell expansion in rheumatoid synovitis. Mol Med 3:452–465
Steiner G, Tohidast-Akrad M, Witzmann G, Vesely M, Studnicka- Benke A, Gal A, Kunaver M, Zenz P, Smolen JS, 1999, Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology, Oxford, 38:202–213
Franz JK, Kolb SA, Hummel KM, Lahrtz F, Neidhart M, Aicher WK, Pap T, Gay RE, Fontana A, Gay S, 1998, Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4 + T lymphocytes in rheumatoid arthritis. Eur J Immunol 28:2661–2671
Mamoune A, Durand V, Le Goff P, Pennec YL, Youinou P, Le Corre R, 2000, Abnormal distribution of CD45 isoforms expressed by CD4 + and CD8 + T cells in rheumatoid arthritis. Histol Histopathol 15:587–591
Hatachi S, Iwai Y, Kawano S, Morinobu S, Kobayashi M, Koshiba M, Saura R, Kurosaka M, Honjo T, Kumagai S, 2003, CD4 + PD-1 + T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid. J Rheumatol 30:1410–1419
van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS, 2004, CD4(+)CD25(+, regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 50:2775–2785
Mottonen M, Heikkinen J, Mustonen L, Isomaki P, Luukkainen R, Lassila O, 2005, CD4 + CD25 + T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol 140:360–367
Mallya RK, Mace BE, 1981, The assessment of disease activity in rheumatoid arthritis using a multivariate analysis. Rheumatol Rehabil 20:14–17
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 321
EP 328
DI 10.1007/s12253-008-9016-1
PG 8
ER
PT J
AU Kobori, L
Nagy, P
Mathe, Z
Hartmann, E
Doros, A
Paku, S
Dezso, K
Sapi, Z
AF Kobori, Laszlo
Nagy, Peter
Mathe, Zoltan
Hartmann, Erika
Doros, Attila
Paku, Sandor
Dezso, Katalin
Sapi, Zoltan
TI Malignant Peripheral Nerve Sheath Tumor of the Liver: A Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Malignant peripheral nerve sheath tumor; Liver; S100; Laminin
ID Malignant peripheral nerve sheath tumor; Liver; S100; Laminin
AB A large, rapidly growing malignant peripheral nerve sheath tumor (MPNST) of the liver in a young female patient, not associated with von Recklinghausen’s disease, is presented. Diagnosis was based on detailed immunohistochemical and electromicroscopic examination beside the characteristic H&E picture. As far as we know, this is the first reported, unambiguously proven "de novo" MPNST in the liver. Differential diagnostic problems are discussed and a review of the literature is given.
C1 [Kobori, Laszlo] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Nagy, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Mathe, Zoltan] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Hartmann, Erika] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Doros, Attila] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Paku, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Dezso, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Sapi, Z (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM zsapi@freemail.hu
CR Schmurun RI, Chibisov VN, 1977, Malignant neurinoma of the liver. Ark Pathol 39:69–71
Young SJ, 1975, Primary malignant neurilemmoma, schwannoma, of the liver in a case of neurofibromatosis. J Pathol 117:151–153
Lederman SM, Martin EC, Laffey KT, Lefkowitch JH, 1987, Hepatic neurofibromatosis, malignant schwannoma, and angiosarcoma in von Recklinghausen’s disease. Gastroenterology 92:234–239
Scheithauer BW, Woodruff JM, Erlandson RA, 1999, Primary malignant tumors of peripheral nerve In Atlas of tumor pathology: Tumors of the Peripheral nervous system, Third Series, Fascicle 24 Washington, DC, Armed Forsis Institute of Pathology, pp 303– 310
Weinberg AG, Finegold MJ, 1983, Primary hepatic tumors in childhood. Hum Pathol 14:512–537
Kiani B, Ferrell LD, Qualman S, Frankel WL, 2006, Immunohistochemical analysis of embryonal sarcoma of the liver. Appl Immunohistochem Mol Morphol 14:193–197
Walker NI, Horn MJ, Strong RW, Lynch SV, Cohen J, Ong TH, Harris OD, 1992, Undifferentiated, embryonal, sarcoma of the liver. Cancer 69:52–59
Fiel MI, Schwarz M, Min AD, Sung MW, Thung SN, 1996, Malignant schwannoma of the liver in a patient without neurofibromatosis. Arch Pathol Lab Med 120:1145–1147
Morikawa Y, Ishihara Y, Matsuura N, 1995, Malignant schwannoma of the liver. Dig Dis Sci 40:1279–1282
Yoshida M, Nakashima Y, Tanaka A, Mori K, Yamaoka Y, 1994, Benign schwannoma of the liver: a case report. Arch Jpn Chir 63:208–214
Hytiroglou P, Linton P, Klion F, Schwartz M, Miller C, Thung SN, 1993, Benign schwannoma of the liver. Arch Pathol Lab Med 117:216–218
Heffron TG, Coventry S, Bedendo F, Baker A, 1993, Resection of primary schwannoma of the liver not associated with neurofibromatosis. Arch Surg 128:1396–1398
Tuder RM, Moraes CF, 1984, Primary semimalignant schwannoma of the liver: light and electron microscopic studies. Pathol Res Pract 178:345–348
Woodruff JM, Selig AM, Crowley K, Allen PW, 1994, Schwannoma, neurilemmoma, with malignant transformation. Am J Surg Pathol 18:882–895
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 329
EP 332
DI 10.1007/s12253-008-9078-0
PG 4
ER
PT J
AU Hardisson, D
Regojo, MR
Marino-Enriquez, A
Martinez-Garcia, M
AF Hardisson, David
Regojo, M Rita
Marino-Enriquez, Adrian
Martinez-Garcia, Mayte
TI Signet-Ring Stromal Tumor of the Ovary: Report of a Case and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Calretinin; Inhibin; Ovary; Sex cord-stromal tumor; Signet-ring stromal tumor
ID Calretinin; Inhibin; Ovary; Sex cord-stromal tumor; Signet-ring stromal tumor
AB Signet-ring stromal tumor of the ovary is extremely rare, with only ten cases reported in the literature. We report on a case of signet-ring stromal tumor of the left ovary in a 54-year-old woman who presented with abdominal discomfort. Histologically, the tumor was composed of an admixture of spindle and round cells which contained a large cytoplasmic vacuole which displaced the nucleus, creating a signet-ring appearance. Numerous cells showed intracytoplasmic hyaline globules. Immunohistochemically, the tumor cells showed positivity for vimentin, actin, inhibin, and calretinin, thus confirming the ovarian stromal origin of the neoplasm. The patient remains free of disease one year and 9 months after surgery. Signet-ring tumor of the ovary is a rare variant of benign ovarian stromal neoplasm and should be distinguished from metastatic mucin-secreting signet-ring adenocarcinoma.
C1 [Hardisson, David] Autonomous University of Madrid, University Hospital La Paz, Department of Pathology, Paseo de la Castellana, 261, 28046 Madrid, Spain.
[Regojo, M Rita] Autonomous University of Madrid, University Hospital La Paz, Department of Pathology, Paseo de la Castellana, 261, 28046 Madrid, Spain.
[Marino-Enriquez, Adrian] Autonomous University of Madrid, University Hospital La Paz, Department of Pathology, Paseo de la Castellana, 261, 28046 Madrid, Spain.
[Martinez-Garcia, Mayte] Autonomous University of Madrid, University Hospital La Paz, Department of Obstetrics and GynecologyMadrid, Spain.
RP Hardisson, D (reprint author), Autonomous University of Madrid, University Hospital La Paz, Department of Pathology, 28046 Madrid, Spain.
EM dhardisson.hulp@salud.madrid.org
CR Ramzy I, 1976, Signet-ring stromal tumor of ovary. Histochemical, light, and electron microscopic study. Cancer 38:166–172
Suarez A, Palacios J, Burgos E et al, 1993, Signet-ring stromal tumor of the ovary: a histochemical, immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat 422:333–366
Dickersin GR, Young RH, Scully RE, 1995, Signet-ring stromal and related tumors of the ovary. Ultrastruct Pathol 19:401–419
Cashell AW, Jerome WG, Flores E, 2000, Signet ring stromal tumor of the ovary occurring in conjunction with Brenner tumor. Gynecol Oncol 77:323–326
Su RM, Chang KC, Chou CY, 2003, Signet-ring stromal tumor of the ovary: a case report. Int J Gynecol Cancer 13:90–93
Vang R, Bague S, Tavassoli FA et al, 2003, Signet-ring stromal tumor of the ovary: clinicopathologic analysis and comparison with Krukenberg tumor. Int J Gynecol Pathol 23:45–51
Deavers MT, Malpica A, Liu J et al, 2003, Ovarian sex cordstromal tumors: an immunohistochemical study including comparison of calretinin and inhibin. Mod Pathol 16:584–590
McCluggage WG, Maxwell P, 2001, Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cordstromal tumors. Histopathology 38:403–408
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 333
EP 336
DI 10.1007/s12253-008-9080-6
PG 4
ER
PT J
AU Kojima, M
Shimizu, K
Sameshima, Sh
Saruki, N
Nakamura, N
AF Kojima, Masaru
Shimizu, Kazuhiko
Sameshima, Shinichi
Saruki, Nobuhiro
Nakamura, Naoya
TI Focal Lymphoid Hyperplasia of the Terminal Ileum Presenting Mantle Zone Hyperplasia with Clear Cytoplasm. A Report of Three Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Focal lymphoid hyperplasia; Terminal ileum; Mantle zone hyperplasia; MALT lymphoma; Immunohistochemistry
ID Focal lymphoid hyperplasia; Terminal ileum; Mantle zone hyperplasia; MALT lymphoma; Immunohistochemistry
AB We report three unusual cases of focal lymphoid hyperplasia of the ileocecal valve. The gross specimens showed thickening of the ileocecal valve. Low power magnification showed a dense lymphoid infiltrate in the mucosa and submucosa. This condition was characterized by reactive lymphoid follicles with large reactive germinal centers surrounded by a pale cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had intermediate- to- medium-sized round or slightly indented nuclei and a broad rim of clear cytoplasm. However, immunohistochemical study demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, sIgM+, sIgD+, CD5−, CD10−, CD23−, CD43−, Bcl-2+,Bcl-6−, CyclinD1−. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. This unusual mantle cell hyperplasia with clear cytoplasm associated with focal lymphoid hyperplasia in middle-aged and elderly patients should be differentiated from the extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type or mantle cell lymphoma showing a marginal zone distribution pattern. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and careful attention should be paid to the morphologic examination.
C1 [Kojima, Masaru] Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 617-1, Takabayashinishi-cho, 373-8550 Ohta, Japan.
[Shimizu, Kazuhiko] Ashikaga Red Cross Hospital, Department of Pathology and Clinical LaboratoriesAshikaga, Japan.
[Sameshima, Shinichi] Gunma Cancer Center Hospital, Department of SurgeryOhta, Japan.
[Saruki, Nobuhiro] Gunma Cancer Center Hospital, Department of AnesthesiologyOhta, Japan.
[Nakamura, Naoya] Tokai University School of Medicine, Department of PathologyIsehara, Japan.
RP Kojima, M (reprint author), Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 373-8550 Ohta, Japan.
EM mkojima@gunma-cc.jp
CR Isaacson PG, Norton AJ, 1994, Extranodal lymphomas. Churchill Livingstone, Edinburgh
Riddell RH, Petras RE, Williams GT et al, 2003, Tumor of the intestine., Atlas of tumor pathology, 3rd series, fascicle 32). Armed Forces Institute of Pathology, Bethesda, MD
Rubin A, Isaacson PG, 1990, Florid reactive lymphoid hyperplasia of the terminal ileum in adults: a condition bearing a close resemblance to low-grade malignant lymphoma. Histopathology 17:19–26
Wan JH, Trainor KJ, Brisco MJ et al, 1990, Monoclonality in B cell lymphoma detected in paraffin wax embedded sections using the polymerase chain reaction. J Clin Pathol 43:888–890
Hunt JP, Chan JA, Samoszuk M et al, 2001, Hyperplasia of mantle/marginal zone B cells with clear cytoplasm in peripheral lymph nodes. A clinicopathologic study of 35 cases. Am J Clin Pathol 116:550–559
Weisenburger DD, Duggan MJ, Perry DA et al, 1991, Non- Hodgkin’s lymphoma of mantle zone origin. Pathol Annu 26I:139–158
Wang T, Lasota J, Hanau CA et al, 1995, Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphoma but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferation is of diagnostic value. APMIS 103:655– 662
Lai R, Weiss LM, Chang KL et al, 1999, Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas. Am J Clin Pathol 111:488–494
Swerdlow SH, Zukerberg LR, Yang W-I et al, 1996, The morphologic spectrum of non-Hodgkin’s lymphomas with BCL1/cyclinD1 gene rearrangements. Am J Surg Pathol 20:627– 640
Anagnostopoulos I, Foss HD, Hummel M et al, 2001, Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma. Histopathology 39:561–565
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 337
EP 340
DI 10.1007/s12253-008-9035-y
PG 4
ER
PT J
AU Farkas, A
Istok, R
Szekely, E
Glasz, T
Kulka, J
AF Farkas, Andrea
Istok, Roland
Szekely, Eszter
Glasz, Tibor
Kulka, Janina
TI Pigmented Papillary Carcinoma: A Rare Tumor of the Male Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; Male breast; Melanin pigment; Papillary carcinoma; Pigmented papillary carcinoma
ID Breast carcinoma; Male breast; Melanin pigment; Papillary carcinoma; Pigmented papillary carcinoma
AB Primary melanin pigment containing tumors of the breast are rare. We report a pigmented papillary carcinoma of a 60-year-old male patient who presented a firm mass 1.7 cm in diameter with an ill defined border on ultrasonography behind the mamilla. To the best of our knowledge this is the third case report of this type of tumor in male breast.
C1 [Farkas, Andrea] St Imre Hospital, Department of Pathology, 12–16 Tetenyi ut, 1115 Budapest, Hungary.
[Istok, Roland] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szekely, Eszter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Glasz, Tibor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Farkas, A (reprint author), St Imre Hospital, Department of Pathology, 1115 Budapest, Hungary.
EM drfarkasandrea@gmail.com
CR Romanelli R, Toncini C, 1986, Pigmented papillary carcinoma of the male breast. Tumori 72:105–108
Saitoh K, Saga K, Okazaki M et al, 1998, Pigmented primary carcinoma of the breast: a clinical mimic of malignant melanoma. Br J Dermatol 139:287–290
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2008
VL 14
IS 3
BP 341
EP 343
DI 10.1007/s12253-008-9075-3
PG 3
ER
PT J
AU Mammas, NI
Sourvinos, G
Giannoudis, A
Spandidos, AD
AF Mammas, N Ioannis
Sourvinos, George
Giannoudis, Athena
Spandidos, A Demetrios
TI Human Papilloma Virus (HPV) and Host Cellular Interactions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Human papilloma virus; HPV; E6; E7; Host cellular proteins; DNA integration
ID Human papilloma virus; HPV; E6; E7; Host cellular proteins; DNA integration
AB Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target and interact with the host cellular proteins. It is generally accepted that Human papilloma virus (HPV) E6 and E7 function as the dominant oncoproteins of ‘high-risk’ HPVs by altering the function of critical cellular proteins. Initially it was shown that HPV E6 enhances the degradation of p53, while HPV E7 inactivates the function of the retinoblastoma tumor suppressor protein Rb. However, recent studies during the last decade have identified a number of additional host cellular targets of both HPV E6 and E7 that may also play an important role in malignant cellular transformation. In this review we present the interactions of HPV E6 and E7 with the host cellular target proteins. We also present the role of DNA integration in the malignant transformation of the epithelial cell.
C1 [Mammas, N Ioannis] University of Crete, Medical School, Department of Virology, 71100 Heraklion, Crete, Greece.
[Sourvinos, George] University of Crete, Medical School, Department of Virology, 71100 Heraklion, Crete, Greece.
[Giannoudis, Athena] University of Liverpool, Faculty of MedicineLiverpool, UK.
[Spandidos, A Demetrios] University of Crete, Medical School, Department of Virology, 71100 Heraklion, Crete, Greece.
RP Spandidos, AD (reprint author), University of Crete, Medical School, Department of Virology, 71100 Heraklion, Greece.
EM spandidos@spandidos.gr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 345
EP 354
DI 10.1007/s12253-008-9056-6
PG 10
ER
PT J
AU Gasperov, MN
Sabol, I
Matovina, M
Spaventi,
Grce, M
AF Gasperov, Milutin Nina
Sabol, Ivan
Matovina, Mihaela
Spaventi, Sime
Grce, Magdalena
TI Detection and Typing of Human Papillomaviruses Combining Different Methods: Polymerase Chain Reaction, Restriction Fragment Length Polymorphism, Line Probe Assay and Sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; Consensus polymerase chain reaction; Restriction fragment length polymorphism; Line probe assay; Sequencing; Type-specific polymerase chain reaction
ID Human papillomavirus; Consensus polymerase chain reaction; Restriction fragment length polymorphism; Line probe assay; Sequencing; Type-specific polymerase chain reaction
AB The identification of the etiological factor of many cervical precancerous lesions and cervical cancer, the human papillomavirus (HPV) is widely used. In this study, we evaluated the consensus and type-specific (TS) polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), line probe assay (LiPA, Innogenetics) and sequencing to determine the HPV types in cervical specimens. Out of 690 High-grade Squamous Intraepithelial Lesion (HSIL) samples, 86.7% were HPV positive and 13.3% HPV negative by consensus primers (MY09/MY11, L1C1/L1C2-1/L1C2-2 and/or GP5/6) directed PCR. Out of 598 HPV positive samples, 85.3%were typed by TS-PCR being HPV 6/11, 16, 18, 31 and/ or 33, while 14.7% remained untyped. Themost prevalent HPV type in the study group was HPV 16, identified in 35.5% cases, while HPV 31 was the second most frequent HPV type with a prevalence of 10.5%. They were followed by HPV types 6/11, 33 and 18 with a prevalence of 7.4%, 6.2% and 4.9%, respectively. Multiple HPV infections with two or more HPV types (6/11, 16, 18, 31 and/or 33) were found in 9.4% cases. A subset of 88 samples was further typed by RFLP and LiPA to determine the rare HPV types in HSIL samples. The most frequent low abundant HPV types in single infections in decreasing order were HPV 53, 58, 66, 56 and 52, while HPV 51 was the most frequent low abundant HPV type found in multiple HPV infections. Multiple HPV infections were mostly found by LiPA in 27.3% cases versus 14.8% cases found by RFLP. The perfect agreement between RFLP and LiPA assay pair was observed only for HPV types 16, 18, 34 and 59 (kappa value of 1). For other HPV types, the inter-assay agreement ranged from very good to no agreement indicating that neither assay is perfect. Sequencing was performed for 33 samples in cases where both RFLP and LiPA were inconclusive. Sequencingwas shown to be a very goodmethod in case of single HPV infection but not applicable in case of multiple HPV infections. Both RFLP and LiPA are good assays for epidemiological studies, although RFLP being cumbersome and time-consuming is less applicable than LiPA. Careful consideration has to be made before the implementation of either HPV typing methods in clinical laboratories.
C1 [Gasperov, Milutin Nina] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
[Sabol, Ivan] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
[Matovina, Mihaela] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
[Spaventi, Sime] Croatian Academy of Science and ArtsZagreb, Croatia.
[Grce, Magdalena] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
RP Grce, M (reprint author), Rudjer Boskovic Institute, Department of Molecular Medicine, Zagreb, Croatia.
EM grce@irb.hr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 355
EP 363
DI 10.1007/s12253-008-9084-2
PG 9
ER
PT J
AU Tao, XH
Shen, Jg
Pan, Wl
Dong, Ye
Meng, Q
Honn, VK
Jin, R
AF Tao, Xiao-Hua
Shen, Jian-gen
Pan, Wei-li
Dong, Yu-e
Meng, Qun
Honn, V Kenneth
Jin, Rongxian
TI Significance of SHP-1 and SHP-2 Expression in Human Papillomavirus Infected Condyloma acuminatum and Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Condyloma acuminatum; Human papillomavirus; Protein tyrosine phosphatase
ID Cervical cancer; Condyloma acuminatum; Human papillomavirus; Protein tyrosine phosphatase
AB Human papillomaviruses (HPVs) are a group of DNA viruses that infect the skin and mucous membranes. Type HPV6/11 is closely related to Condyloma acuminatum, while HPV16/18 is the principal cause of cervical cancer. In this study, we examined the expression of protein tyrosine phosphatases SHP-1 and SHP-2 in Condyloma acuminatum, cervical cancer and the relationship between SHP-1/SHP2 expression and HPV infection. Forty Condyloma acuminatum cases, 20 cervical cancer cases and 20 normal human foreskins were examined for HPV infection by in situ hybridization and the expression of SHP-1 and SHP-2 were examined by immunohistochemistry. Results demonstrated that positive expression rates of HPV6/11, HPV16/18, and HPV31/33 were 98%, 10%, and 7.5% in Condyloma acuminatum, 10%, 85%, and 25% in cervical cancer. Only one normal foreskin demonstrated positive staining for HPV16/18. Positive expression rates of SHP-1 and SHP-2 were 80% and 85% in Condyloma acuminatum, 85% and 90% in cervical cancer. The SHP-1 and SHP-2 expressions were mainly distributed in the prickle layer of Condyloma acuminatum and were diffusely distributed in cervical cancer cells. Only 35% and 30% of foreskins demonstrated weak staining in the basal layer cells. There were statistically significant correlations among the infection of HPV and the expression of SHP-1 and SHP-2 in both Condyloma acuminatum and cervical cancer (P<0.05). SHP-1 expression has a positive correlation with SHP-2 expression. Our results demonstrate putative roles of SHP-1 and SHP-2 in the progression of both Condyloma acuminatum and cervical cancer after HPV infection.
C1 [Tao, Xiao-Hua] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Shen, Jian-gen] Medical College of Zhejiang University, Research Institute of ImmunityHangzhou, China.
[Pan, Wei-li] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Dong, Yu-e] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Meng, Qun] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Honn, V Kenneth] Wayne State University, Department of Pathology, 430 Chemistry Building, 48202 Detroit, MI, USA.
[Jin, Rongxian] Wayne State University, Department of Pathology, 430 Chemistry Building, 48202 Detroit, MI, USA.
RP Jin, R (reprint author), Wayne State University, Department of Pathology, 48202 Detroit, USA.
EM rongxianj@wayne.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 365
EP 371
DI 10.1007/s12253-008-9065-5
PG 7
ER
PT J
AU Liu, Y
Xu, LM
Zhong, HH
Heng, JW
Wu, QB
AF Liu, Yan
Xu, Lin Mei
Zhong, Hao Hao
Heng, Jie Wan
Wu, Quan Bing
TI EGFR Mutations are More Frequent in Well-Differentiated than in Poor-Differentiated Lung Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemotherapy; Epidermal growth factor receptor; Lung adenocarcinoma; Polymerase chain reaction; Sequence analysis
ID Chemotherapy; Epidermal growth factor receptor; Lung adenocarcinoma; Polymerase chain reaction; Sequence analysis
AB Somatic mutations in epidermal growth factor receptor (EGFR) tyrosine kinase domain, particularly deletions in exon 19 and point mutation in exon 21, are associated with clinical outcome in patients with lung adenocarcinoma, suggesting that EGFR mutation would have an important role in clinical decision making. DNA was extracted from the excised specimens of 60 lung adenocarcinoma patients with phenol-chloroform and ethanol precipitation. Exon 19 and 21 were amplified by PCR, and direct sequenced from both sense and antisense directions. EGFR somatic mutations were present in 13 of 60 patients (21.67%), including seven cases of in-frame deletion in exon 19 around codon 746 and six cases of amino acid substitution in exon 21. Exon 21 mutation is more frequent in adenocarcinomas with bronchi-alveolar component than exon 19 deletions. Mutations were more prevalent in well-differentiated adenocarcinomas (9/27, 33.33%) than in moderate to poor-differentiated adenocarcinomas (4/33, 12.12%) (P<0.05). Adenocarcinomas with bronchi-alveolar components had higher mutation frequency (8/22,36. 36%) than those without bronchi-alveolar components (5/38, 13.16%) (P<0.05). In this study, female patients had more mutation rate than male patients. This trend was also observed in the patients with pathologic stage I–II compared with stage III–IV, but neither of them was statistically significant. Patients with cisplatin-based adjuvant chemotherapy had no significantly prolonged survival compared with single radical resection. But patients with EGFR mutation had relative longer survival. In conclusion, our study suggest that EGFR mutations may be a valuable prognostic factor for disease free survival of surgically treated lung adenocarcinoma patients independently from adjuvant chemotherapy.
C1 [Liu, Yan] Health Science Center, Peking University, Department of Pathology, 100191 Beijing, China.
[Xu, Lin Mei] Tianjin Chest Hospital, Department of Pathology, 300051 Tianjin, China.
[Zhong, Hao Hao] Health Science Center, Peking University, Department of Pathology, 100191 Beijing, China.
[Heng, Jie Wan] Health Science Center, Peking University, Department of Pathology, 100191 Beijing, China.
[Wu, Quan Bing] Health Science Center, Peking University, Department of Pathology, 100191 Beijing, China.
RP Liu, Y (reprint author), Health Science Center, Peking University, Department of Pathology, 100191 Beijing, China.
EM laylaly@126.com
CR Paez JG, Janne PA, Lee JC et al, 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500
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Mitsudomi T, Kosaka T, Endoh H et al, 2005, Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 23:2513–2520
Qin BM, Chen X, Zhu JD et al, 2005, Identification of EGFR kinase domain mutations among lung cancer patients in China: implication of targeted cancer therapy. Cell Res 15:212–217
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 373
EP 379
DI 10.1007/s12253-008-9113-1
PG 7
ER
PT J
AU Menegazzo, M
Bagatella, P
Marson, P
Donadel, C
De Silvestro, G
Corsini, A
AF Menegazzo, Marinella
Bagatella, Paola
Marson, Piero
Donadel, Carla
De Silvestro, Giustina
Corsini, Augusto
TI Reduced Mobilisation of Hematopoietic Stem Cells After Hepatic Resection for Malignant Liver Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hematopoietic stem cell; Liver resection; Cancer; CD34+ mobilisation
ID Hematopoietic stem cell; Liver resection; Cancer; CD34+ mobilisation
AB Recent studies have demonstrated that hematopoietic stem cells (HSCs) can mobilize following liver resection, thus contributing to the repair of hepatic damage. Aim of this study has been to determine whether the nature of the hepatic lesion (benign vs. malignant disease) can give rise to a different degree of mobilisation of HSCs. Two groups of patients were selected: the first included seven patients undergoing hepatic resection (five major and two minor) for a benign liver disease (focal nodular hyperplasia, hemangioma cavernosa, angioma, biliary adenofibroma) and the second included seven patients undergoing hepatic resection (five major and two minor) for a malignant (either primary or secondary) liver disease. White blood cell count and CD34+ (percentage and total number) at time T0 (basal value before surgery) and at time T1 (value on the sixth–eighth day after surgery) have been evaluated by standard methods. In the group undergoing hepatic resection for a benign liver disease, a significant increase of CD34+ cells, both in percentage (0.082±0.043 vs. 0.048±0,026, p=0.041) and in absolute number (8.14±5.95 vs. 3.26±2.63, p=0.018) have been documented, as opposed to the group of patients affected with a malignant liver disease, where no significant variation has been observed (CD34+ %: 0.044±0.033 vs. 0.041±0.031, p: n.s.; CD34+ total number: 3.52±2.56 vs. 2.27±2.01, p=n.s.) These results show a different bone marrow response to the surgical liver resection depending on the nature of the lesion, thus emphasizing a reduced mobilisation of HSCs in the malignant diseases. Since it has been documented that the type of the hepatic lesion can induce a different regenerative response, it has to be explained how the neoplastic lesions can negatively influence the mobilization of HSCs. It can be hypothesized that a variety of humoral factors, including stromal cellderived factor, matrix metalloproteinases, hepatocyte growth factor and interleukin-8 can influence the process of mobilization of HSCs after liver resection surgery. These substances are also involved in the mechanisms of development and metastasising of many tumours. It is probably in this context that a reason may be found for the different mobilisation of hematopoietic stem cells, depending on the nature of the hepatic lesion treated, that was encountered in this study.
C1 [Menegazzo, Marinella] Azienda Ospedale Universita, Division of Surgery, 35128 Padova, Italy.
[Bagatella, Paola] Azienda Ospedale Universita di Padova, Blood Transfusion Service, via Giustiniani 2Padova, Italy.
[Marson, Piero] Azienda Ospedale Universita di Padova, Blood Transfusion Service, via Giustiniani 2Padova, Italy.
[Donadel, Carla] Azienda Ospedale Universita di Padova, Blood Transfusion Service, via Giustiniani 2Padova, Italy.
[De Silvestro, Giustina] Azienda Ospedale Universita di Padova, Blood Transfusion Service, via Giustiniani 2Padova, Italy.
[Corsini, Augusto] Azienda Ospedale Universita, Division of Surgery, 35128 Padova, Italy.
RP Marson, P (reprint author), Azienda Ospedale Universita di Padova, Blood Transfusion Service, Padova, Italy.
EM piero.marson@sanita.padova.it
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 381
EP 385
DI 10.1007/s12253-008-9091-3
PG 5
ER
PT J
AU Ueki, T
Ohashi, K
Jinta, M
Okuyama, Y
Hiruma, K
Akiyama, H
Sakamaki, H
AF Ueki, Toshimitsu
Ohashi, Kazuteru
Jinta, Minako
Okuyama, Yoshiki
Hiruma, Kiyoshi
Akiyama, Hideki
Sakamaki, Hisashi
TI Delayed Hematological Recovery Following Autologous Transplantation Utilizing Peripheral Blood Stem Cells Harvested After Treatment with Arsenic Trioxide
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Arsenic trioxide; Acute promyelocytic leukemia; Delayed hematological recovery; Autologous PBSCT
ID Arsenic trioxide; Acute promyelocytic leukemia; Delayed hematological recovery; Autologous PBSCT
AB We describe herein two cases of delayed hematological recovery (DHR) following autologous peripheral blood stem cell transplantation (auto-PBSCT) using cells harvested during second molecular remission after treatment with arsenic trioxide (As2O3). Current therapeutic strategies with As2O3 plus auto-PBSCT might be hampered by potential mechanisms of DHR. Our observations highlight the need for study of the real effects of As2O3 on the kinetics of normal hematopoietic engraftment following auto-PBSCT.
C1 [Ueki, Toshimitsu] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Jinta, Minako] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Okuyama, Yoshiki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center, Transfusion Medicine and Cell Therapy DivisionTokyo, Japan.
[Hiruma, Kiyoshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center, Transfusion Medicine and Cell Therapy DivisionTokyo, Japan.
[Akiyama, Hideki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Ohashi, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM k.ohashi@cick.jp
CR Soignet SL, Maslak P, Wang Z-G, et al, 1998, Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 339:1341–1348
Niu C, Yan H, Sun HP, et al, 1999, Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 94:3315–3324
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Douer D, Tallman MS, 2005, Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol 23:2396–2410
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 387
EP 390
DI 10.1007/s12253-008-9049-5
PG 4
ER
PT J
AU Kovacs, TG
Barany, O
Schlick, B
Csoka, M
Gado, J
Ponyi, A
Muller, J
Nemeth, J
Hauser, P
Erdelyi, JD
AF Kovacs, T Gabor
Barany, Olga
Schlick, Barbara
Csoka, Monika
Gado, Judit
Ponyi, Andrea
Muller, Judit
Nemeth, Julia
Hauser, Peter
Erdelyi, J Daniel
TI Late Immune Recovery in Children Treated for Malignant Diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Humoral immunity; Cellular immunity; Late effects; Malignant diseases; Children
ID Humoral immunity; Cellular immunity; Late effects; Malignant diseases; Children
AB In this study we analyzed the recovery of the immune system in children after completion of the therapy. We analysed 88 children (51 boys, 37 girls, mean age at diagnosis: 7.8 years) receiving chemotherapy for malignant diseases (43 acute lymphoblastic leukemia, 15 lymphoma, 20 bone tumor, ten other solid tumors). Serum immunoglobulin levels (Ig), natural killer activity (NK), antibodydependent cellular cytotoxicity (ADCC) and T and B cell proliferation were determined 1 year after cessation of therapy. The mean levels of Ig were in the normal range at a mean of 13 months after chemotherapy (IgG: 11.2±3.3, IgA: 1.6±0.9, IgM: 1.0±0.5 g/l), however in the leukemic patients serum IgG was below the lower limit of the normal range in 3/43 (7.0%) cases, serum IgA was low in 5/43 (11.6%) and serum IgM was decreased in 4/43 (9.3%) cases. In the solid tumor patients IgG values were within the normal range and only 2–2/45 children had lower values for IgA and IgM (4.4%). NK activity decreased in 7/43 (16.3%) leukemic patients, and in 3/45 (6.7%) solid tumor patients, ADCC decreased in 8/43 (18.6%) and 3/45 (6.7%), respectively (p<0.001). B-cell blastic transformation was decreased in 3/43 (7%) leukemic patients and in 4/45 (8.9%) solid tumor patients. At the same time T-cell blastic transformation was altered in 5/43 (11.6%) and in 4/45 (8.9%) cases, respectively. Leukemic patients had significantly more infections during the first year after chemotherapy than solid tumor patients (1.60±1.18 vs 0.96±1.14; p=0.011). No significant correlations could be found between the investigated immune parameters and the number and severity of infections. It is concluded, that cytotoxic therapy can lead to long-term depression of the immune system, first of all in leukemic patients.
C1 [Kovacs, T Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Barany, Olga] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Schlick, Barbara] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Gado, Judit] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Ponyi, Andrea] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Muller, Judit] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Nemeth, Julia] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Hauser, Peter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Erdelyi, J Daniel] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kovacs, TG (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM kovi@gyer2.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 391
EP 397
DI 10.1007/s12253-008-9073-5
PG 7
ER
PT J
AU Ghaffari, HS
Obeidi, N
Dehghan, M
Alimoghaddam, K
Gharehbaghian, A
Ghavamzadeh, A
AF Ghaffari, H Seyed
Obeidi, Narghes
Dehghan, Mehdi
Alimoghaddam, Kamran
Gharehbaghian, Ahmad
Ghavamzadeh, Ardashir
TI Monitoring of Cytomegalovirus Reactivation in Bone Marrow Transplant Recipients by Real-time PCR
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cytomegalovirus; Cyclosporine; pp65 Antigenemia; Real-time PCR; TaqMan
ID Cytomegalovirus; Cyclosporine; pp65 Antigenemia; Real-time PCR; TaqMan
AB Cytomegalovirus (CMV) has been recognized as the most important viral pathogen in persons undergoing bone marrow transplantation (BMT). The aim was to develop a quantitative PCR assay to quantify CMV DNA in peripheral blood leukocytes (PBLs) of bone marrow transplantation (BMT) patients. An in-house real-time PCR assay based on TaqMan technology was developed to monitor the quantity of CMV DNA in PBLs of the BMT recipients. Sequential blood samples (415 specimens) were collected from 43 patients as weekly intervals until day 100 after transplantation. The CMV DNA was quantified in parallel with the pp65 antigenemia assay in PBL samples. Viral reactivation occurred in 51% and 41.8% of the recipients as detected by RQ-PCR and antigenemia assays respectively. There was a significant correlation between both assays (P<0.0001); however, the RQ-PCR was more sensitive than the antigenemia. CMV DNA was detected by the RQ-PCR by a median of 14 days earlier than the antigenemia. Preemptive therapy was implemented in the antigenemia positive cases. The administration of ganciclovir led to a rapid decrease in the viral load. After preemptive therapy, the antigenemia achieved a negative result earlier than the RQ-PCR assay (a median of 17.5 days). An increase of viral load in both quantitative assays and of cyclosporine serum level were identified as the most significant risk factors for CMV reactivation. The quantitative CMV PCR might be a useful tool for monitoring the CMV reactivation and guiding the efficacy of the CMV preemptive therapy in BMT recipients.
C1 [Ghaffari, H Seyed] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow Transplantation, 11411 Tehran, Iran.
[Obeidi, Narghes] Iranian Blood Transfusion Organization Research CenterTehran, Iran.
[Dehghan, Mehdi] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow Transplantation, 11411 Tehran, Iran.
[Alimoghaddam, Kamran] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow Transplantation, 11411 Tehran, Iran.
[Gharehbaghian, Ahmad] Iranian Blood Transfusion Organization Research CenterTehran, Iran.
[Ghavamzadeh, Ardashir] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow Transplantation, 11411 Tehran, Iran.
RP Ghaffari, HS (reprint author), Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow Transplantation, 11411 Tehran, Iran.
EM shghaffari2000@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 399
EP 409
DI 10.1007/s12253-008-9030-3
PG 11
ER
PT J
AU Illes,
Simon, Zs
Toth, E
Rosta, A
Miltenyi, Zs
Molnar, Zs
AF Illes, Arpad
Simon, Zsofia
Toth, Erika
Rosta, Andras
Miltenyi, Zsofia
Molnar, Zsuzsa
TI Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)—Clinicopathological Features Based on the Data of Two Hungarian Lymphoma Centres
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nodular lymphocyte predominant Hodgkin lymphoma; Classical Hodgkin lymphoma; Differential diagnosis; Immunohistochemistry; Treatment; Prognosis
ID Nodular lymphocyte predominant Hodgkin lymphoma; Classical Hodgkin lymphoma; Differential diagnosis; Immunohistochemistry; Treatment; Prognosis
AB Clinicopathological features of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) differ from those of the classical Hodgkin lymphoma (cHL). Our aim was to examine clinical presentation, therapeutic and survival results of NLPHL patients in Hungary based on the data of two centres, and incidentally we analyzed the clinicopathological characteristics and differential diagnostic difficulties of this rare entity. We analyzed the clinical features, treatment and survival data of 536 Hodgkin lymphoma patients who had been diagnosed and primarily treated in our institutes between 1995 and 2004. Mean follow-up time was 82.7 (3–144) months of the total 536 HL patients. Sixteen (3%) of the patients were diagnosed with NLPHL, 93% of them presented with early-stage disease. None of the patients showed extranodal or splenic involvement or bulky disease. One patient received chemotherapy alone, six received only involved field radiotherapy while six underwent combined modality treatment. We applied watch and wait strategy in three cases. Overall response rate was 100% (93.75% complete). Two NLPHL cases transformed to non-Hodgkin’s lymphoma. In contrast to the classical HL, the 10-year prognosticated overall survival rate was 100 vs. 82%, the event free survival was: 75% vs. 70%. In NLPHL group there were no late or multiple relapses and none of them died. Conclusions: NLPHL is a rare disease, thus these are limited experiences with its diagnosis and treatment. Since the disease has an excellent outcomeit is very important to prefer less toxic or local therapies to reach long term survival similar to that of the normal population.
C1 [Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
[Simon, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
[Toth, Erika] National Institute of OncologyBudapest, Hungary.
[Rosta, Andras] National Institute of OncologyBudapest, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
[Molnar, Zsuzsa] National Institute of OncologyBudapest, Hungary.
RP Simon, Zs (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
EM zsocogo@gmail.com
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Diehl V, Sextro M, Franklin J et al, 1999, Clinical presentation, course and prognostic factors in lymphocyte-predominant Hodgkin’s disease and lymphocyte-rich classical Hodgkin’s disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin’s Disease. J Clin Oncol 17:776–783
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Jaffe E, Harris NL, Stein H et al, 2001, Pathology and genetics of tumors of haematopoetic and lymphoid tissues. IARC, Lyon, France pp 240–243
Rahemtullah A, Reichard KK, Dorn ME et al, 2007, Doublepositive CD4+CD8+ T-cell populations in nodular lymphocyte predominant Hodgkin lymphoma: further charachterization and relationship to other entities. Haematologica Suppl 5:2
Harris NL, 1998, The many faces of Hodgkin’s disease around the world: what have we learned from its pathology? Ann Oncol 9, 5):S45–S56
Pajor L, 2002, Hodgkin lymphomas: current presentation of pathogenesis and patomorphology. Orv Hetil 143(13):651–661
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Dogan A, Burke JS, Goteri G et al, 2003, Micronodular T-cell/ histiocyte-rich large B-cell lymphoma of the spleen. Histology, immunophenotype and differential diagnosis. Am J Surg Pathol 27:903–911
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Hutchings M, Loft A, HansenM(2006, Different histopathological subtypes of Hodgkin lymphoma show significantly different levels of FDG uptake. Hematol Oncol 24:146–150
Wirth A, Yuen K, Barton M, 2005, Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: a retrospective multicenter study of the Australian Radiation Oncology Lymphoma Group. Cancer 104:1221–12229
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Mittal BB, Nalesnik M, Composite, 1986, lymphoma, Hodgkin’s and non-Hodgkin’s, of the spleen in a previously untreated patient. Acta Hematol 76:29–32
Sundeen JT, Cossman J, Jaffe ES, 1988, Lymphocyte predominant Hodgkin’s disease nodular subtype with coexistent ‘large cell lymphoma’. Histological progression or composite malignancy? Am J Surg Pathol 12:599–606
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 411
EP 421
DI 10.1007/s12253-008-9043-y
PG 11
ER
PT J
AU Nyari, AT
Kajtar, P
Bartyik, K
Thurzo, L
McNally, R
Parker, L
AF Nyari, Andras Tibor
Kajtar, Pal
Bartyik, Katalin
Thurzo, Laszlo
McNally, Richard
Parker, Louise
TI Seasonal Variation of Childhood Acute Lymphoblastic Leukaemia is Different Between Girls and Boys
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Childhood acute lymphoblastic leukaemia; Gender specific seasonal effect; Male predominance; Simple harmonic regression
ID Childhood acute lymphoblastic leukaemia; Gender specific seasonal effect; Male predominance; Simple harmonic regression
AB The aim of this study was to investigate seasonal trends in the incidence of acute lymphoblastic leukaemia (ALL) around the times of birth and diagnosis in children aged 0–4 years and also to examine gender specific effects. Children born in South Hungary during 1981–1997 were analysed. Registrations of first malignancies for children, diagnosed under age 5 years before the end of 2002 were obtained from the Hungarian Paediatric Oncology Group providing a representative sample of Hungarian children over a 17 year period of time. Data were available on the corresponding numbers of births for each month of the study period were obtained. Statistical analyses were performed using logistic regression with harmonic components. The study analysed 121 cases of children, aged under 5 years, who were diagnosed with ALL. We found no seasonal effect related to date of diagnosis. However, there was seasonal variability for ALL related to date of birth. Maximal rates were seen in children born in February and August in the simple harmonic regression model for all children diagnosed with ALL. Analysis by gender found evidence of seasonality related to month of birth with peaks in February and August in boys, but different seasonal effects were seen for girls (peak in November, nadir in May). Our study provides some evidence that male specific immune responses to infections around the time of birth could explain the male predominance in the incidence of ALL.
C1 [Nyari, Andras Tibor] University of Szeged, Department of Medical Informatics, Koranyi fasor 9, 6720 Szeged, Hungary.
[Kajtar, Pal] University of Pecs, Department of PediatricsPecs, Hungary.
[Bartyik, Katalin] University of Szeged, Department of PediatricsSzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of OncotherapySzeged, Hungary.
[McNally, Richard] Newcastle University, Paediatric and Lifecourse Epidemiology Research GroupNewcastle upon Tyne, UK.
[Parker, Louise] Dalhousie University, IWK Health Centre, Department of PediatricsHalifax, Canada.
RP Nyari, AT (reprint author), University of Szeged, Department of Medical Informatics, 6720 Szeged, Hungary.
EM nyari@dmi.u-szeged.hu
CR Alexander FE, Boyle P, Carli PM et al, 1998, Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project. Brit J Cancer 77:812–817
Kinlen LJ, 1989, Infective cause of childhood leukaemia. Lancet 1(8634):378–379
Knox EG, Gilman EA, 1997, Hazard proximities of childhood cancers in Great Britain from 1953–80. J Epidemiol Comm Health 51:151–159
McNally RJQ, Eden TOB, 2004, An infectious aetiology for childhood leukaemia: a review of the evidence. Brit J Haematol 127:243–263
Thorne R, Hunt LP, Mott MG, 1998, Seasonality in the diagnosis of childhood acute lymphoblastic leukaemia. Brit J Cancer 77:678
Nyari TA, Kajtar P, Bartyik K, Thurzo L, Parker L, 2006, Childhood acute lymphoblastic leukaemia in relation to population mixing around the time of birth in South Hungary. Pediatric Blood Cancer 47:944–948
Jakab Zs, Balogh E, Kiss Cs, Olah E, 2002, Epidemiologic studies in a population-based childhood cancer registry in Northeast Hungary. Medical Pediatric Oncol 38:338–344
Central Demographic Agency 1982–1998 Demographic yearbook Central Demographic Agency. Budapest
Stolwijk AM, Straatman H, Zielhuis GA, 1999, Studying seasonality by using sine and cosine functions in regression analysis. J Epidemiol Community Health 53:235–238
Kajtar P, Fazekasne KM, Mehes K, 2003, Month of birth in childhood acute lymphoblastic leukemia. Orv Hetil 144:1869– 1871
Westerbeek RM, Blair V, Eden OB et al, 1998, Seasonal variation in the onset of childhood leukemia and lymphoma. Brit J Cancer 78:119–124
Badrinath P, Day NE, Stockton D, 1997, Seasonality in the diagnosis of acute lymphocytic leukaemia. Brit J Cancer 75:1711–1713
Ross JA, Severson RK, Swensen AR et al, 1999, Seasonal variations in the diagnosis of childhood cancer in the United States. Brit J Cancer 81:549–553
Karimi M, Yarmohammadi H, 2003, Seasonal variations in the onset of childhood leukemia/lymphoma: April 1996 to March 2000, Shiraz, Iran. Hematol Oncol 21:51–55
Sorensen HT, Olsen JH, Rothman KJ, 2001, Seasonal variation in month of birth and diagnosis of early childhood acute lymphoblastic leukemia. JAMA 285:168–169
Feltbower RG, Pearce MS, Dickinson HO et al, 2001, Seasonality of birth for cancer in Northern England, UK. Paediatric Perinatal Epidemiol 15:338–345
Higgins CD, dos-Santos-Silva I, Stiller CA, Swerdlow AJ, 2001, Season of birth and diagnosis of children with leukaemia: an analysis of over 15 000 UK cases occurring from 1953–95. Brit J Cancer 84:406–412
Lopman BA, Reacher M et al, 2003, A summertime peak of “winter vomiting disease": surveillance of noroviruses in England and Wales, 1995 to 2002. BMC Public Health 3:13
Green MS, 1992, The male predominance in the incidence of infectious diseases in children: a postulated explanation for disparities in the literature. Int J Epidemiol 21:381– 386
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Peltola H, 1982, Observations on the seasonal variation of the most common acute pediatric diseases in the Helsinki area, Finland). J Comm Health 7:159–170
Dorak MT, Oguz FS, Yalman N et al, 2002, A male-specific increase in the HLA-DRB4, DR53, frequency in high-risk and relapsed childhood ALL. Leuk Res 26:651–656
Kinlen LJ, 1995, Epidemiological evidence for an infective basis in childhood leukaemia. Brit J Cancer 71:1–5
Greaves MF, 1997, Aetiology of acute leukaemia. Lancet 349:344–349
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 423
EP 428
DI 10.1007/s12253-008-9017-0
PG 6
ER
PT J
AU Varkonyi, J
Szakaly, D
Janoskuti, L
Hosszufalusi, N
Panczel, P
Karadi, I
Schoket, B
AF Varkonyi, Judit
Szakaly, Dora
Janoskuti, Livia
Hosszufalusi, Nora
Panczel, Pal
Karadi, Istvan
Schoket, Bernadette
TI Glutathione S-Transferase Enzyme Polymorphisms in a Hungarian Myelodysplasia Study Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myelodysplastic syndrome; GSTM1; GSTT1; GSTP1; Genetic polymorphism
ID Myelodysplastic syndrome; GSTM1; GSTT1; GSTP1; Genetic polymorphism
AB GSTM1, GSTT1 and GSTP1 Ile105Val that are members of the GST gene family encode for Phase II drug/xenobiotic metabolizing enzymes, primarily with detoxifying function, and are polymorphic in humans. GSTM1 and GSTT1 homozygous deletion genotypes do not express the enzymes. It has been hypothesised that individuals with homozygous deletion of the GSTM1 and/or GSTT1 gene may have lower detoxification capacity towards genotoxic agents therefore those individuals may be at increased risk of myelodysplastic syndrome which is a preleukemic condition. Genetic polymorphism of GSTM1, GSTT1 and GSTP1 Ile105Val was investigated in a case–control study in a Hungarian patient population comprising 86 patients with myelodysplastic syndrome and 99 hospital-based controls. There were no statistically significant differences between cases and controls for the GSTM1, GSTT1 and GSTP1 Ile105Val genotype frequencies for any of the three genes separately and in various combinations. This suggests that these genetic polymorphisms may not be strong risk factors, if any, for myelodysplastic syndrome.
C1 [Varkonyi, Judit] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Szakaly, Dora] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Janoskuti, Livia] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Hosszufalusi, Nora] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Panczel, Pal] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Karadi, Istvan] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Schoket, Bernadette] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kornyezet-egeszsegugyi IntezetBudapest, Hungary.
RP Varkonyi, J (reprint author), Semmelweis University, 3rd Department of Internal Medicine, 1125 Budapest, Hungary.
EM varkjud@kut.sote.hu
CR Farrow A, Jacobs A, West RR, 1989, Myelodysplasia, chemical exposure and other environmental factors. Leukemia 3:33–35
Kim SY, Choi JK, Cho YH, Chung EJ, Paek D, Chung HW, 2004, Chromosomal aberrations in workers exposed to low levels of benzene: association with genetic polymorphisms. Pharmacogenetics 14:453–463
Mannervik B, Danielson H, 1988, Glutathione transferases— structure and catalytic activity. CRC Crit Rev Biochem 23:283– 337
Vineis P, Malats N, Lang M, d’Errico A, Caporaso N, Cuzick J, Boffetta P, eds,, 1999, Metabolic polymorphisms and susceptibility to cancer. International Agency for Research on Cancer, Lyon, pp 51–62
Lin DX, Tang YM, Peng Q, Lu SX, Ambrosone CB, Kadlubar FF, 1998, Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1 and M1 and cytochrome P450 2E1. Cancer Epidemiol Biomark Prev 7:1013– 1018
Geisler S, Olshan A, 2001, GSTM1, GSTT1 and risk of head and neck cancer: a mini-HuGE review. Am J Epidemiol 154:95–105
Watson MA, Stewart PK, Smith GB, Massey TE, Bell DA, 1998, Human glutathione S-transferase P1 polymorphisms, relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19:275–280
Srivastava SK, Singhal SS, Hu X, Awasthi YC, Zimniak P, Singh SV, 1999, Differential catalytic efficiency of allelic variants of human glutathione S-transferase α in catalyzing the glutathione conjugation of thiothepa. Arch Biochem Biophys 366:89–94
Lecomte T, Landi B, Beaune Ph, Puig PL, Lirot MA, 2006, Glutathione S-transferase P1 polymorphism, Ile 105 Val, predicts cumulative neuropathy in patients receiving oxiplatin-based chemotherapy. Clin Cancer Res 12:3050–3056
Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD, Bell DA, 1996, Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1, GSTT1, gene defect. Lancet 347:295–297
Ozawa S, Schoket B, McDaniel LP, Tang Y-M, Ambrosone CB, Kostic Sz, Vincze I, Adlubar FF, 1999, Analyses of bronchial bulky DNA adduct levels and CYP2C9, GSTP1 and NQO1 genotypes in a Hungarian study population with pulmonary diseases. Carcinogenesis 20:991–995
Landi S, 2000, Mammalian class theta GST and different susceptibility to carcinogens: a review. Mutat Res 463:247–283
Cotton SC, Sharp L, Little J, Brockton N, 2000, Gluthation Stransferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol 151:7–32
Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL, Baranova H, Bathum L, Benhamou S, Boffetta P, Bouchardy C, Breskvar K, Brockmoller J, Cascorbi I, Clapper ML, Coutelle C, Daly A, Dell’Omo M, Dolzan V, Dresler CM, Fryer A, Haugen A, Hein DW, Hildesheim A, Hirvonen A, Hsieh LL, Ingelman-Sundberg M, Kalina I, Kang D, Kihara M, Kiyohara C, Kremers P, Lazarus P, Le Marchand L, Lechner MC, van Lieshout EM, London S, Manni JJ, Maugard CM, Morita S, Nazar-Stewart V, Noda K, Oda Y, Parl FF, Pastorelli R, Persson I, Peters WH, Rannug A, Rebbeck T, Risch A, Roelandt L, Romkes M, Ryberg D, Salagovic J, Schoket B, Seidegard J, Shields PG, Sim E, Sinnet D, Strange RC, Stucker I, Sugimura H, To-Figueras J, Vineis P, Yu MC, Taioli E, 2001, Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomark Prev 10:1239–1248
Atoyebi W, Kusec R, Fidler C, Peto TEA, Boultwood J, Wainscoat JS, 1997, Glutathione S-transferase gene deletions in myelodysplasia. Lancet 349:1450–1451
Sasai Y, Horiike S, Misawa S, Kaneko H, Kobayashi M, Fujii H, Kashima K, Taniwaki M, 1999, Genotype of glutathione Stransferase and other genetic configurations in myelodysplasia. Leuk Res 23:975–981
Ozbek U, Aydin-Sayitoglu M, Hatirnaz O, Erensoy N, 2005, Role of CYP1A1, CYP2E1, GSTT1 and GSTM1 genes in the susceptibility to acute leukemias. Haematologica S2: Abstr 0585
Tsabouri S, Georgiou I, Alamanso I, Bourantas KL, 2000, Increased prevalence of GSTM1 null genotype in MDS patients. Acta Haematol 104:169–173
Arruda VR, Lima CS, Grignoli CR, deMelo MB, Lorand-Metze I, Alberto FL, Saad ST, Costa FF, 2001, Increased risk for acute myeloid leukaemia in individuals with glutathion S-transferase mu-1, GSTM1, and theta 1, GSTT1, gene defects. Eur J Haematol 66:383–388
Davies SM, Robinson LL, Buckley JD, Radolff GA, Ross JA, Perentesis JP, 2000, Gluthation S-transferase polymorphisms in children with myeloid leukemia: a Children’s Cancer Group study. Cancer Epidemiol Biomark Prev 9:563–566
Haase D, Schulz TG, Heutelbeck A, Fonatsch C, Harder L, Griesinger F, Hallier E, Trumper L, 2003, Polymorphisms of metabolizing enzymes, NAT2, GSTT1, GSTM1 and GSTP1, in de novo and therapy-induced MDS and AML. 7th International Symposium onMyelodysplastic Syndromes. Leuk Res 27(1):S1–S2
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 429
EP 433
DI 10.1007/s12253-008-9008-1
PG 5
ER
PT J
AU Murillo-Ortiz, B
Perez-Luque, E
Malacara, MJ
Daza-Benitez, L
Hernandez-Gonzalez, M
Benitez-Bribiesca, L
AF Murillo-Ortiz, Blanca
Perez-Luque, Elva
Malacara, Manuel Juan
Daza-Benitez, Leonel
Hernandez-Gonzalez, Martha
Benitez-Bribiesca, Luis
TI Expression of Estrogen Receptor Alpha and Beta in Breast Cancers of Pre- and Post-menopausal Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Estrogen receptor; Estradiol; Breast cancer
ID Estrogen receptor; Estradiol; Breast cancer
AB Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in preand post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p<0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar postmenopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p<0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.
C1 [Murillo-Ortiz, Blanca] Unidad de Investigacion en Epidemiologia Clinica, Unidad Medica de Alta Especialidad No. 1 Bajio, Instituto Mexicano del Seguro Social, UMAE No. 1 Bajio, IMSS, B. Lopez Mateos Esq. Insurgentes S/N, Colonia: Los Paraisos, CP 37320 Leon, Guanajuato, Mexico.
[Perez-Luque, Elva] Universidad de Guanajuato, Instituto de Investigaciones MedicasLeon, Guanajuato, Mexico.
[Malacara, Manuel Juan] Universidad de Guanajuato, Instituto de Investigaciones MedicasLeon, Guanajuato, Mexico.
[Daza-Benitez, Leonel] Unidad de Investigacion en Epidemiologia Clinica, Unidad Medica de Alta Especialidad No. 1 Bajio, Instituto Mexicano del Seguro Social, UMAE No. 1 Bajio, IMSS, B. Lopez Mateos Esq. Insurgentes S/N, Colonia: Los Paraisos, CP 37320 Leon, Guanajuato, Mexico.
[Hernandez-Gonzalez, Martha] Unidad de Investigacion en Epidemiologia Clinica, Unidad Medica de Alta Especialidad No. 1 Bajio, Instituto Mexicano del Seguro Social, UMAE No. 1 Bajio, IMSS, B. Lopez Mateos Esq. Insurgentes S/N, Colonia: Los Paraisos, CP 37320 Leon, Guanajuato, Mexico.
[Benitez-Bribiesca, Luis] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades OncologicasMexico City, DF, Mexico.
RP Murillo-Ortiz, B (reprint author), Unidad de Investigacion en Epidemiologia Clinica, Unidad Medica de Alta Especialidad No. 1 Bajio, Instituto Mexicano del Seguro Social, CP 37320 Leon, Mexico.
EM bomo907@hotmail.com;blanca.murillo@imss.gob.mx
CR Deroo BJ, Korach KS, 2006, Estrogen receptors and human disease. J Clin Invest 116:561–570
Greene G, Gilna P, Waterfield M, Baker A, Hart Y, Shine J, 1986, Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150–1154
Mosselman S, Polman J, Dijkema R, 1996, ERb: Identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49–53
Moore J, Mckee D, Slentz-Kesler K, Moore L, Jones S, Horne E et al, 1998, Cloning and characterization of human estrogen receptor β isoforms. Biochem Byophis Res Commun; 247:75–78
Gustafsson JA, 2000, An update on estrogen receptors. Semin Perinatol 24:66–69
Hall JL, McDonnell P, 1999, The estrogen receptor b isoform, ERb, of the human estrogen receptor modulates ERa transcriptional activity and it a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140:5566–5578
Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S et al, 1997, Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors, alpha, and, beta). Endocrinology 138:863–870
Speirs V, Skliris GP, Burdall SE, Carder PJ, 2002, Distinct expression patterns of ERα and ERβ in normal human mammary gland. J Clin Pathol 55:371–374
Murillo-Ortiz B, Perez-Luque E, Malacara JM, 2005, Mammographic density and the relationship with the PvuII and XbaI genotypes estrogen receptors alpha, ERa, polymorphisms. Ginecol Obstet Mex 73:229–233
Simpson ER, Mahendroot MS, Means GD et al, 1994, Aromatase cytocrome P450, the enzyme reponsible for estrogen biosynthesis. Endocrinol Rev 15:342–355
Meza-Munoz DE, Fajardo ME, Perez-Luque EL, Malacara JM, 2006, Factors associated with estrogen receptors-alpha, ERalpha, and -beta, ER-beta, and progesterone receptor abundance in obese and non obese pre- and post-menopausal women. Steroids 71(6):498–503
Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P, 2004, Loss of ERb expression as a common step in estrogen-dependent tumor progression. Endocrine-Related Cancer 11:537–551
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 435
EP 442
DI 10.1007/s12253-008-9088-y
PG 8
ER
PT J
AU Bujas, T
Pavic, I
Lenicek, T
Mijic, A
Kruslin, B
Davor, T
AF Bujas, Tatjana
Pavic, Ivana
Lenicek, Tanja
Mijic, August
Kruslin, Bozo
Davor, Tomas
TI Peritumoral Retraction Clefting Correlates with Advanced Stage Squamous Cell Carcinoma of the Esophagus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophagus; Metastases; Peritumoral clefting; Squamous cell carcinoma; Tumor stage
ID Esophagus; Metastases; Peritumoral clefting; Squamous cell carcinoma; Tumor stage
AB The present study was designated to analyze correlation between the presence and extent of peritumoral retraction clefting and various clinicopathologic features in esophageal squamous cell carcinoma (ESCC), and to possibly establish the significance of this phenomenon in ESCC. Fifty-four consecutive patients with advanced ESCC were included in the study. The presence of peritumoral retraction clefting was classified on the basis of the proportion of tumor nests exhibiting this phenomenon. Tumors with clefts that affected up to 25% of tumor nests were classified as group I; with clefts that affected >25% to 50% of tumor nests as group II; with clefts that affected >50% to 75% of tumor nests as group III; and tumors with clefts that affected more than 75% of tumor nests were classified as group IV. Statistical analysis showed a correlation between presence and extent of peritumoral clefting and lymph node metastasis. T3 tumors and tumors with lymph node metastasis had significantly more pronounced peritumoral clefting compared with T2 tumors and tumors without lymph node metastasis. The presence of peritumoral clefting was not associated with the number of affected lymph nodes. There was no correlation between the presence and extent of peritumoral clefting with patient age and sex, and tumor location, diameter and grade. The association of peritumoral retraction clefting in ESCC with local invasiveness and lymph node metastasis indicated that peritumoral clefting could be a simple and useful morphological feature of tumor aggressiveness and may contribute to the pathological and clinical assessment of patients with ESCC.
C1 [Bujas, Tatjana] Karlovac General Hospital, Department of Pathology, Andrije Stampara 3, HR-47000 Karlovac, Croatia.
[Pavic, Ivana] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29, HR-10000 Zagreb, Croatia.
[Lenicek, Tanja] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29, HR-10000 Zagreb, Croatia.
[Mijic, August] Sestre Milosrdnice University Hospital, University Department of Surgery, Vinogradska 29, HR-10000 Zagreb, Croatia.
[Kruslin, Bozo] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29, HR-10000 Zagreb, Croatia.
[Davor, Tomas] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29, HR-10000 Zagreb, Croatia.
RP Davor, T (reprint author), University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, HR-10000 Zagreb, Croatia.
EM dtomas@kbsm.hr
CR Hashibe M, Boffetta P, Janout Vet al, 2007, Esophageal cancer in Central and Eastern Europe: tobacco and alcohol. Int J Cancer 120:1518–1522
Strnad M, ed,, 2007, National Cancer Registry. Cancer incidence in Croatia 2005. Bulletin No.30, Croatian National Institute of Public Health, Zagreb
Hamilton SR, Aaltonen LA, eds,, 2001, WHO classification of tumours. Pathology and genetics of tumours of the digestive system. IARC, Lyon
Sleeman JP, 2000, The lymph node as a bridgehead in the metastatic dissemination of tumors. Recent Results Cancer Res 157:55–81
Clarijs R, Ruiter DJ, de Waal RM, 2001, Lymphangiogenesis in malignant tumours: does it occur? J Pathol 193:143–146
Tomas D, Kruslin B, 2004, The potential value of, myo, fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma. Prostate 61:324–331
Cheng MF, Tzao C, Tsai WC et al, 2006, Expression of EMMPRIN and matriptase in esophageal squamous cell carcinoma: correlation with clinicopathological parameters. Dis Esophagus 19:482–486
Kruslin B, Tomas D, Rogatsch H et al, 2003, Periacinar retraction clefting in the prostatic needle core biopsies: an important diagnostic criterion or a simple artifact? Virchows Arch 443:524–527
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Ulamec M, Tomas D, Ensinger C et al, 2007, Periacinar retraction clefting in proliferative prostatic atrophy and prostatic adenocarcinoma. J Clin Pathol 60:1098–1101
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Kruslin B, Tomas D, Cviko A et al, 2006, Periacinar clefting and p63 immunostaining in prostatic intraepithelial neoplasia and prostatic carcinoma. Pathol Oncol Res 12:205–209
Tomas D, Ulamec M, Hudolin T et al, 2006, Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma. Prostate Cancer Prostatic Dis 9:414–419
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Ingber DE, 2002, Cancer as a disease of epithelial–mesenchymal interactions and extracellular matrix regulation. Differentiation 70:547–560
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Tomakidi P, Stark HJ, Herold-Mende C et al, 2003, Discriminating expression of differentiation markers evolves in transplants of benign and malignant human skin keratinocytes through stromal interactions. J Pathol 200:298–307
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 443
EP 447
DI 10.1007/s12253-008-9038-8
PG 5
ER
PT J
AU Yuan, A
Liu, J
Liu, Y
Bjornsen, T
Varro, A
Cui, G
AF Yuan, Aping
Liu, Jinzhong
Liu, Yiqing
Bjornsen, Tone
Varro, Andrea
Cui, Guanglin
TI Immunohistochemical Examination of Gastrin, Gastrin Precursors, and Gastrin/CCK-2 Receptor in Human Esophageal Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophagus; Squamous cell carcinoma; Gastrin; Immunohistochemistry
ID Esophagus; Squamous cell carcinoma; Gastrin; Immunohistochemistry
AB A promoting effect of gastrin on stimulating Barrett’s oesophagus proliferation has been demonstrated, but whether it plays a regulating role for esophageal squamous cell carcinoma (ESCC) to date has not been fully investigated. The aim of this study is to examine the expressions of gastrin, gastrin precursors and gastrin/CCK-2 receptor in ESCC. Tissue specimen sections from 38 patients with ESSC obtained from a high incidence area of north China were assessed using immunohistochemistry for amidated gastrin, gastrin precursors (progastrin and glycine-extended gastrin) and gastrin/CCK-2 receptors. Their clinical histopathological significance was also analyzed. Of 38 ESCC, the immunoreactivities of gastrin, glycineextended gastrin and progastrin were observed in 13.2% (5/38), 7.9% (3/38) and 23.68% (9/38) cases. The expression of progastrin was obviously higher than other gastrins, though not significantly (P>0.05). In positive cases for gastrin or glycine-extended gastrin, the scores of positive tumor cell numbers were at a lower density (<10/abundantdistributed field). However, the scores of progastrin positive tumor cell density in five of nine positive cases were over 10/abundant-distributed field. The immunoreactivity of gastrin/CCK-2 receptor was also observed in 15.8% (6/38) ESCC cases. There was not significant correlation regarding immunohistochemical results with known histomorphological parameters i.e. gender, tumor location and TNM stages. Based on our current results, ESCC tumor cells could be a possible cellular source of gastrin precursors, which has been postulated to play a role in regulating the growth in some human tumor cells.
C1 [Yuan, Aping] Faculty of Medicine, University of Tromso, Institute of Clinical Medicine, Laboratory of Gastroenterology, 9037 Tromso, Norway.
[Liu, Jinzhong] the Fourth Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, Henan, China.
[Liu, Yiqing] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
[Bjornsen, Tone] University Hospital of North, Department of PathologyTromso, Norway.
[Varro, Andrea] University of Liverpool, Physiology LaboratoryLiverpool, UK.
[Cui, Guanglin] Faculty of Medicine, University of Tromso, Institute of Clinical Medicine, Laboratory of Gastroenterology, 9037 Tromso, Norway.
RP Cui, G (reprint author), Faculty of Medicine, University of Tromso, Institute of Clinical Medicine, Laboratory of Gastroenterology, 9037 Tromso, Norway.
EM guanglin.cui@fagmed.uit.no
CR Parkin DM, Bray FI, Devesa SS, 2001, Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):S4–S66
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 449
EP 455
DI 10.1007/s12253-008-9047-7
PG 7
ER
PT J
AU Ersoz, S
Sert, H
Yandi, M
Erem, C
Mungan, S
Ersoz, OH
Cobanoglu, U
Hacihasanoglu, A
AF Ersoz, Safak
Sert, Hikmet
Yandi, Mustafa
Erem, Cihangir
Mungan, Sevdegul
Ersoz, Onder Halil
Cobanoglu, Umit
Hacihasanoglu, Arif
TI The Significance Of Galectin-3 Expression in the Immunocytochemical Evaluation of Thyroid Fine Needle Aspiration Cytology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid neoplasms; Galectin-3
ID Thyroid neoplasms; Galectin-3
AB The aim of this study is to evaluate the significance of immunohistochemical expression of Galectin-3 in the differential diagnosis of benign and malignant thyroid nodules. We studied the fine needle aspiration specimens of 38 patients who had evaluated for nodular goiter and undergone a thyroid surgery between 2004–2005. Slides had been stained immunocytochemically with Galectin-3. The cytoplasmic staining of Galectin-3 was analyzed. Three cases of five follicular carcinomas had positive staining for Galectin-3, while two had not. Two cases with follicular adenomas were negative for Galectin-3. Five cases of six papillary carcinomas had positive staining for Galectin-3, while one case (the case with a papillary microcarcinoma) had not. The single cases with medullary and anaplastic carcinomas were negative for Galectin-3. None of the cases with a benign thyroid pathology had positive staining for Galectin-3. Galectin-3 immunocytochemical staining, had a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3% for thyroid malignancies. For the evaluation of follicular neoplasm, Galectin-3 immunocytochemical staining had a sensitivity of 60%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Galectin-3 expression in thyrocytes is a strong indicator of a malignant proliferative lesion especially for papillary and to an extent in follicular thyroid neoplasms. Galectin-3 could be used as a supplementary marker for cytological diagnosis.
C1 [Ersoz, Safak] Karadeniz Technical University, Faculty of Medicine, Department of Pathology, 61080 Trabzon, Turkey.
[Sert, Hikmet] Karadeniz Technical University, Faculty of Medicine, Department of General Surgery, 61080 Trabzon, Turkey.
[Yandi, Mustafa] Karadeniz Technical University, Faculty of Medicine, Department of General Surgery, 61080 Trabzon, Turkey.
[Erem, Cihangir] Karadeniz Technical University, Faculty of Medicine, Department of Endocrinology, 61080 Trabzon, Turkey.
[Mungan, Sevdegul] Karadeniz Technical University, Faculty of Medicine, Department of Pathology, 61080 Trabzon, Turkey.
[Ersoz, Onder Halil] Karadeniz Technical University, Faculty of Medicine, Department of Endocrinology, 61080 Trabzon, Turkey.
[Cobanoglu, Umit] Karadeniz Technical University, Faculty of Medicine, Department of Pathology, 61080 Trabzon, Turkey.
[Hacihasanoglu, Arif] Karadeniz Technical University, Faculty of Medicine, Department of Endocrinology, 61080 Trabzon, Turkey.
RP Ersoz, S (reprint author), Karadeniz Technical University, Faculty of Medicine, Department of Pathology, 61080 Trabzon, Turkey.
EM ersozs@yahoo.com
CR Gasbarri A, Martegani MP, Del Prete F, Lucante T, Natali PG, Bartolazzi A, 1999, Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 17:3494– 3502
Nunez C, Mendelsohn G, 1989, Fine-needle aspiration and needle biopsy of the thyroid gland. Pathol Annu 24:161–198
Gharib H, 1994, Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations and effect. Mayo Clin Proc 69:44–49
Segura MEA, Magalhaes AV, 2005, Galectin-3 immunostaining in the thyroid neoplasms. J Bras Patol Med Lab 41:341–346
Caraway NP, Sneige N, Saman NA, 1993, Diagnostic pitfalls in thyroid fine-needle aspiration: a review of 394 cases. Diagn Cytopathol 9:345–350
Chiarotti L, Berlingieri MT, De Rosa P et al, 1992, Increased expression of the negative growth factor, galactoside-binding protein gene, in transformed thyroid cells and in human thyroid carcinomas. Oncogene 71:2507–2511
Inohara H, Akahani S, Koths K, Raz A, 1996, Interactions between galectin-3 and Mac-2-binding protein mediate cell–cell adhesion. Cancer Res 56:4530–4534
Inohara H, Raz A, 1995, Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. Cancer Res 55: 3267–3271
Bartolazzi A, Gasbarri A, Papotti M et al, 2001, Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650
Inohara H, Honjo Y, Yoshii T et al, 1999, Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms. Cancer 85:2475–2484
Cvejic D, Savin S, Paunovic I, Tatic S, Havelka M, Sinadinovic J, 1998, Immunohistochemical localization of galectin-3 in malignant and benign human thyroid tissue. Anticancer Res 18:2637–2641
Schlinkert RT, van Heerden JA, Goelnerr JR et al, 1997, Factors that predict malignant thyroid lesions when fine-needle aspiration is “suspicious for follicular neoplasm”. Mayo Clin Proc 72:913–916
Tuttle RM, Lemar H, Burch HB, 1998, Clinical features associated with an increased risk of thyroid malignancy in patients follicular neoplasia by fine-needle aspiration. Thyroid 8:377–383
Xu XC, El-Naggar AK, Lotan R, 1995, Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol 147:815–822
Kim MJ, Kim HJ, Hong SJ, Shong YK, Gong G, 2006, Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions. Acta Cytol 50:28–34
Mehrotra P, Okpokam A, Bouhaidar R et al, 2004, Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 45:493–500
Kovacs RB, Foldes J, Winkler G, Bodo M, Sapi Z, 2003, The investigation of galectin-3 in diseases of the thyroid gland. Eur J Endocrinol 149:449–453
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 457
EP 460
DI 10.1007/s12253-008-9041-0
PG 4
ER
PT J
AU Kurita, H
Kamata, T
Koike, T
Kobayashi, H
Kurashina, K
AF Kurita, Hiroshi
Kamata, Takahiro
Koike, Takeshi
Kobayashi, Hiroichi
Kurashina, Kenji
TI Intraoperative Tissue Staining of Invaded Oral Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intraoperative; Surgery; Tissue staining; Invasion; Surgical margin
ID Intraoperative; Surgery; Tissue staining; Invasion; Surgical margin
AB The purpose of this study was to assess the ability of intraoperative tissue staining with consecutive application of 0.4% indigo carmine and 0.5% Congo red to demonstrate the extent and border of oral carcinoma invasion. Seventeen patients were included in the study. Once the oral tumor was resected, a vertical section of surgical specimen was taken from the central part of the tumor. The extent and border of the invaded carcinoma were assessed on digital microscopic examination with tissue staining. The results of assessments were compared with corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. Tissue staining produced a brown-black stain on normal muscle, connective, and salivary tissues but not tumor and epithelial tissues. It clearly demonstrated the extent and border of tumor invasion in 13 of 17 patients (76.5%); however, detection of remnant vital tumor cells in scar tissue after neoadjuvant chemotherapy, and distinction between the tumor and adipose tissue scattered in the muscle tissue was difficult. The results of this study showed that intraoperative tissue staining was a possible method in demonstrating the extent and border of carcinoma deeply invaded in the soft tissue and selecting the site for additional frozen section analysis, although the method needed some refinement.
C1 [Kurita, Hiroshi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Kamata, Takahiro] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Koike, Takeshi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Kobayashi, Hiroichi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Kurashina, Kenji] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
RP Kurita, H (reprint author), Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 390-8621 Matsumoto, Japan.
EM hkurita@shinshu-u.ac.jp
CR Lee JG, 1974, Detection of residual carcinoma of the oral cavity, oropharynx: a study of surgical margins. Trans Am Acad Ophthalmol Otolaryngol 78:49–53
Byers RM, Bland KI, Borlase B, Luna M, 1978, The prognostic and therapeutic value of frozen section determinations in the surgical treatment of squamous carcinoma of the head and neck. Am J Surg 136:525–528
Ribeiro NFF, Godden DRP, Wilson GE, Butterworth DM, Woodwards RTM, 2003, Do frozen sections help achieve adequate surgical margins in the resection of oral carcinoma? Int J Oral Maxillofac Surg 32:152–158
Gooris PJJ, Vermey B, de Visscher JGAM, Roodenburg JLN, 2003, Frozen section examination of the margins for resection of squamous cell carcinoma of the lower lip. J Oral Maxillofac Surg 61:890–894
Kurita H, Uehara S, Funamoto S, Nakatsuka A, Kobayashi H, Kurashina K, 2006, Intraoperative digital microscopic assessment of the deep surgical margins in oral carcinoma surgery: a preliminary report. Am J Surg 191:84–88
Jung M, Kiesslich R, 1999, Chromoendoscopy and intravital staining techniques. Baillieres Best Pract Res Clin Gastroenterol 13:11–19
Fennerty MB, 1999, Tissue staining, chromoscopy, of the gastrointestinal tract. Can J Gastroenterol 13:423–429
Tatsua M, Okuda S, Tamura H, Taniguchi H, 1982, Endoscopic diagnosis of early gastric cancer by the endoscopic Congo redmethylene blue test. Cancer 50:2956–2960
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 461
EP 465
DI 10.1007/s12253-008-9074-4
PG 5
ER
PT J
AU Mejia, C
Ruiz-Azuara, L
AF Mejia, Carmen
Ruiz-Azuara, Lena
TI Casiopeinas IIgly and IIIia Induce Apoptosis in Medulloblastoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cell survival; Cisplatin; MTT method; Mitochondria; Actin; Copper
ID Cell survival; Cisplatin; MTT method; Mitochondria; Actin; Copper
AB The medulloblastoma is a tumor of the central nervous system that is expressed in childhood. Casiopeinas® are a family of molecules with an active copper 2+ core and an amino acid sequence that seem give them tumoral specificity. The mechanism of action is poorly understood; however, it has been reported that some metals such as copper and some of their complexes are toxic due to their high potential to participate in redox reactions which could cause apoptosis in medulloblastoma cells. Cell survival was measured by the MTT method and apoptosis was identified by the presence of condensed nuclei, disruption of the mitochondrial transmembrane potential, and cytoskeleton disorder. In all cases medulloblastoma cells treated with Casiopeinas showed more apoptotic features than untreated cells. Casiopeinas IIgly and IIIia promise to be important compounds for the treatment of medulloblastoma, mainly by their ability to induce apoptosis.
C1 [Mejia, Carmen] UNAM-Campus Juriquilla, Instituto de Neurobiologia, Departamento de Neurobiologia Molecular y Celular, Boulevard Universitario 3001, C.P. 76230 Queretaro, Mexico.
[Ruiz-Azuara, Lena] UNAM, Facultad de Quimica, Departamento de Quimica InorganicaMexico City, Mexico.
RP Mejia, C (reprint author), UNAM-Campus Juriquilla, Instituto de Neurobiologia, Departamento de Neurobiologia Molecular y Celular, C.P. 76230 Queretaro, Mexico.
EM maria.c.mejia@uv.es
CR Allen JC, Bloom J, Ertel I et al, 1986, Brain tumors in children: current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Semin Oncol 13:110–122
Bloom HJ, 1982, Medulloblastoma in children. Increasing survival rates and further prospects. Int J Radiat Oncol Biol Phys 8:2023–2027
Charras GT, Yarrow JC, Horton MA et al, 2005, Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435:365–369
Coleman ML, Sahai EA, Yeo M et al, 2001, Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol 3:339–345
Cotter TG, Lennon SV, Glynn JM et al, 1992, Microfilamentdisrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis. Cancer Res 52:997–1005, Erratum in: Cancer Res 52:3512, 1992
Davis S, Weiss MJ, Wong JR et al, 1985, Mitochondria and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinomaderived MCF-7 cells. J Biol Chem 260:13844–13850
Decaudin D, Marzo I, Brenner C et al, 1998, Mitochondria in chemotherapy-induced apoptosis: a prospective novel target of cancer therapy. Int J Oncol 12:141–152
Ferrer G, Ruiz-Ramirez L, Radi R, 1997, Ternary copper complexes and manganese, III, tetrakis, 4-benzoic acid)(porphyrin, catalyze peroxynitrite-dependent nitration of aromatics. J Chemical Res Toxicol 10:1338–1344
Fuentes-Noriega I, Ruiz-Ramirez L, Tovar Tovar A et al, 2002, Development and validation of a liquid chromatographic method for Casiopeina IIIi in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci 772:115–121
Koya K, Li Y, Wang H et al, 1996, MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation. Cancer Res 56:538–543
Marin-Hernandez A, Gracia-Mora I, Ruiz-Ramirez L et al, 2003, Toxic effects of copper-based antineoplastic drugs, Casiopeinas, on mitochondrial functions. Biochem Pharmacol 65:1979–1989
Moss DK, Betin VM, Malesinski SD et al, 2006, A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation. J Cell Sci 119:2362–2374
Nicotera P, Melino G, 2004, Regulation of the apoptosis-necrosis switch. Oncogene 23:2757–2765
Ruiz-Azuara L, 1994, Procedimiento para la obtencion de complejos metalicos como agentes anticancerigenos. Tipo I. Patente de invencion en tramite, SECOFI 18801. P. I., 1990). Patente, Enero 26, no. 172967
Siro S, Minoru T, Kazuo U et al, 1998, Requirement of caspase-3, -like, protease-mediated hydrogen peroxide production for apoptosis induced by various anticancer drugs. J Biol Chem 273:26900–26907
Skehan P, Storeng R, Scudiero D et al, 1990, New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112
Titulo de Marca, 1992, Casiopeina. Reg. 407543 SECOFI
Trejo-Solis C, Palencia G, Zuniga S et al, 2005, Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspasedependent and caspase-independent mechanisms. Neoplasia 7:563–574
Van GM, Festjens N, Van LG et al, 2003, Mitochondrial intermembrane proteins in cell death. Biochem Biophys Res Commun 304:487–497
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 467
EP 472
DI 10.1007/s12253-008-9060-x
PG 6
ER
PT J
AU Bely, M
Apathy,
AF Bely, Miklos
Apathy, Agnes
TI Recurrent Pancreatic Arteritis and Vasculogenic Relapsing Pancreatitis in Rheumatoid Arthritis – A Retrospective Clinicopathologic and Immunohistochemical Study of 161 Autopsy Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rheumatoid arthritis; Vasculitis; Pancreatitis
ID Rheumatoid arthritis; Vasculitis; Pancreatitis
AB The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.
C1 [Bely, Miklos] St John's Hospital, Department of Pathology, Frankel Leo u. 17-19, H-1027 Budapest, Hungary.
[Apathy, Agnes] National Institute for Rheumatology and PhysiotherapyBudapest, Hungary.
RP Bely, M (reprint author), St John's Hospital, Department of Pathology, H-1027 Budapest, Hungary.
EM dr.bely.miklos@t-online.hu
CR de Prado NI, de la Calle CMA, de Prado NJM, Sanchez GF, Medranda MA, 2005, Vascular complications of pancreatitis. Rev Clin Esp 205:326–332
Mendelson RM, Anderson J, Marshall M, Ramsay D, 2005, Vascular complications of pancreatitis. ANZ J Surg 75:1073– 1079
de Araujo TS, Kirsner RS, 2001, Vasculitis: wounds 13:99–110
Tada M, Naruse S, Arai A et al, 2004, An autopsy case of systemic vasculitis associated with hepatitis C virus-related mixed cryoglobulinemia presenting severe peripheral neuropathy. Rinsho Shinkeigaku 44:686–690
Pagnoux C, Mahr A, Cohen P, Guillevin L, 2005, Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg–Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine, Baltimore, 84:115–128
Christl SU, Borchard F, Keller R et al, 2004, Pancreatic tail tumor as an unusual first manifestation of Wegener’s disease. Z Gastroenterol 42:513–516
Swol-Ben J, Bruns CJ, Muller-Ladner U et al, 2004, Leukoencephalopathy and chronic pancreatitis as concomitant manifestations of systemic lupus erythematosus related to anticardiolipin antibodies. Rheumatol Int 24:177–181
Iwasa S, Katoh R, 2005, Autopsy case of microscopic polyangiitis with crescentic glomerulonephritis and necrotizing pancreatitis. Pathol Int 55:520–523
Haraguchi K, Gunji K, Ito Y, Yokomori N et al, 2005, Extensive pancreatic necrosis in microscopic polyangiitis. Clin Exp Nephrol 9:326–331
Hidaka T, Suzuki K, Kawakami M et al, 1992, An autopsy case of malignant rheumatoid arthritis, MRA, which was difficult to distinguish from polyarteritis nodosa, PN). Ryumachi 32:318–326
O’Neil KM, Jones DM, Lawson JM, 1992, Wegener’s granulomatosis masquerading as pancreatic carcinoma. Dig Dis Sci 37:702–704
Romhanyi G, 1971, Selective differentiation between amyloid and connective tissue structures based on the collagen specific topo-optical staining reaction with congo red. Virchows Arch 354:209–222
Romhanyi G, 1979, Selektive Darstellung sowie methodologische Moglichkeiten der Analyse ultrastruktureller Unterschiede von Amyloidablagerungen. Zbl Allg Pathol Pathol Anat 123:9–16
Wright JR, Calkins E, Humphrey RL, 1977, Potassium permanganate reaction in amyloidosis. Lab Invest 36:274–281
Bely M, Apathy A, 1999, Systemic secondary, AA, amyloidosis in rheumatoid arthritis. In: Kyle RA, Gertz MA, eds, Amyloid and amyloidosis 1998. USA Parthenon Publishing, New York– London, pp 408–410
Bely M, 2006, Histochemical differential diagnosis and polarization optical analysis of amyloid and amyloidosis. The Scientific World Journal 6: 154–168, in memoriam of Professor G Romhanyi, September 15, 1905 to August 29, 1991; http://www. thescientificworld.com/SCIENTIFICWORLDJOURNAL/toc/ TSWJ_ArticleLanding.asp?ArticleId=1899 http://www.abstracts2- view.com/eular/)
Cruickshank B, 1954, The arteritis of rheumatoid arthritis. Ann Rheum Dis 13:136–146
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Eulderink F, 1976, Doodsoorzak: rheumatoide arthritis. Ned T Geneesk 120:357–363
Albada-Kuipers VGA, Bruijn JA, Westedt M-L, Breedveld FC, Eulderink F, 1986, Coronary arteritis complicating rheumatoid arthritis. Ann Rheum Dis 45:963–965
Boers M, Croonen AM, Dijkmans BA, Breedveld FC, Eulderink F, Cats A, Weening JJ, 1987, Renal finding in rheumatoid arthritis: clinical aspect of 132 necropsies. Ann Rheum Dis 46:658–663
Suzuki A, Ohosone Y, Obana M, Mita S, Matsuoka Y, Irimajiri S, Fukuda J, 1994, Cause of death in 81 autopsied patients with rh reumatoid arthritis. J Rheumatol 21:33–36
Bely M, Apathy A, 2002, Systemic vasculitis in rheumatoid arthritis: the frequency, severity and stages of vasculitis in various organs – a retrospective clinicopathologic study of 161 autopsy patients, Abstract). Ann Rheum Dis 61(Suppl 1):394. http://www. abstracts2view.com/eular/
Bely M, Apathy A, 2002, Histologic characteristics of systemic vasculitis in rheumatoid arthritis: the types of vasculitis and size of blood vessels involved by vasculitis – a retrospective clinicopathologic study of 161 autopsy patients, Abstract). Ann Rheum Dis 61(Suppl 1):394–395. http://www.abstracts2view. com/eular/
Bely M, Apathy A, 2006, Szovodmenyek es tarsult megbetegedesek rheumatoid arthritisben – a 234 elhunyt beteg patologiai es klinikai adatainak retrospektiv elemzese alapjan. Orvosi Hetilap 147:1063–1076
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 473
EP 480
DI 10.1007/s12253-008-9026-z
PG 8
ER
PT J
AU Kullmann, T
Barta, I
Csiszer, E
Antus, B
Horvath, I
AF Kullmann, Tamas
Barta, Imre
Csiszer, Eszter
Antus, Balazs
Horvath, Ildiko
TI Differential Cytokine Pattern in the Exhaled Breath of Patients with Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Proteomics; Exhaled breath condensate; Microarray. Biomarker
ID Lung cancer; Proteomics; Exhaled breath condensate; Microarray. Biomarker
AB Tumour cells may alter the protein pattern of biological samples resulting in specific differences that may aid diagnosis and treatment. In this pilot study we tested the cytokine pattern of exhaled breath condensate of patients with lung cancer. Breath condensates collected from 50 smoking patients with lung cancer and 25 smokers without clinical or radiological sign of a pulmonary tumour but having co-morbidities with similar severity as those with lung cancer were pooled for antibody microarray analysis testing 120 cytokines in parallel. Every cytokine on the array gave a signal in both groups. Nine cytokines including eotaxin, FGFs, IL-10 and MIP-3 were present with more than two-fold difference between the two groups. Large number of cytokines is present in the exhaled breath. Further analysis of specific differences associated with lung cancer may have clinical importance.
C1 [Kullmann, Tamas] National Koranyi Institute for TB and Pulmonology, Department of PathophysiologyBudapest, Hungary.
[Barta, Imre] National Koranyi Institute for TB and Pulmonology, Department of PathophysiologyBudapest, Hungary.
[Csiszer, Eszter] National Koranyi Institute for TB and Pulmonology, Department of PulmonologyBudapest, Hungary.
[Antus, Balazs] National Koranyi Institute for TB and Pulmonology, Department of PathophysiologyBudapest, Hungary.
[Horvath, Ildiko] Semmelweis University, Institute of Morphology and Physiology, Ulloi street 78/a, 1082 Budapest, Hungary.
RP Horvath, I (reprint author), Semmelweis University, Institute of Morphology and Physiology, 1082 Budapest, Hungary.
EM hildiko@elet2.sote.hu
CR Hultschig C, Kreutzberger J, Seitz H et al, 2006, Recent advances of protein microarrays. Curr Opin Chem Biol 10:4–10
Zhong L, Coe SP, Stromberg AJ et al, 2006, Profiling tumorassociated antibodies for early detection of non-small cell lung cancer. J Thoracic Oncol 1:513–519
Horvath I, Hunt J, Barnes PJ, on behalf of the ERS/ATS TaskForce, 2005, Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J 26:523– 548
Matsunaga K, Yanagisawa S, Ichikawa T et al, 2006, Airway cytokine expression measured by means of protein microarray in exhaled breath condensate: correlation with physiologic properties in asthmatic patients. J Allergy Clin Immunol 118:84–90
Czebe K, Barta I, Antus B et al, 2008, Influence of condensing equipment and temperature on exhaled breath condensate pH, total protein and leukotriene concentrations. Respir Med 102: 720–725, Epub 2008 Jan 31
Ko FW, Lau CY, Leung TF et al, 2006, Exhaled breath condensate levels of eotaxin and macrophage-derived chemokine in stable adult asthma patients. Clin Exp Allergy 36:44–51
Leung TF, Wong GW, Ko FWet al, 2004, Increased macrophagederived chemokine in exhaled breath condensate and plasma from children with asthma. Clin Exp Allergy 34:786–791
Sack U, Scheibe R, Wotze lM et al, 2006, Multiplex analysis of cytokines in exhaled breath condensate. Cytometry A 69:169–172
Dimberg J, Hugander A, Wagsater D, 2006, Protein expression of the chemokine, CCL28, in human colorectal cancer. Int J Oncol. 28:315–319
Kwabi-Addo B, Ozen M, Ittmann M, 2004, The role of fibroblast growth factors and their receptors in prostate cancer. Endocr Relat Cancer 11:709–724
Szilasi M, Dolinay T, Nemes Z et al, 2006, Pathology of chronic obstructive pulmonary disease. Pathol Oncol Res 12:52–60
Phillips M, Cataneo RN, Cummin AR et al, 2003, Detection of lung cancer with volatile markers in the breath. Chest 123:2115– 2123
Machado RF, Laskowski D, Deffenderfer O et al, 2005, Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 171:1286–1291
Elek G, Lapis K, 2006, A path or a new road in laboratory diagnostics? Biological mass spectrometry: facts and perspectives. Pathol Oncol Res 12:178–183
Laszlo K, Jozsef T, 2005, Genomics of lung cancer may change diagnosis, prognosis and therapy. Pathol Oncol Res 11:5–10
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 481
EP 483
DI 10.1007/s12253-008-9046-8
PG 3
ER
PT J
AU Zaka, Z
Fodor, J
Udvarhelyi, N
Orosz, Zs
Kasler, M
AF Zaka, Zoltan
Fodor, Janos
Udvarhelyi, Nora
Orosz, Zsolt
Kasler, Miklos
TI Subcutaneous Calcification as a Delayed Complication of Radiotherapy: A Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Ichthyosis; Hodgkin’s disease; Radiotherapy; Subcutaneous calcification
ID Ichthyosis; Hodgkin’s disease; Radiotherapy; Subcutaneous calcification
AB Subcutaneous calcification following radiotherapy is a very rare late complication. Here we report a case of radiotherapy for Hodgkin’s disease in a patient with ichthyosis. Our review of the literature revealed that subcutaneous calcifications occurred in previously normal skin following irradiation. In our case the calcification developed in abnormal skin after telecobalt radiotherapy for mediastinal Hodgkin’s disease. Ichthyosis is a systemic cutaneous disease and may increase the risk of late radiation complications.
C1 [Zaka, Zoltan] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Fodor, Janos] National Institute of Oncology, Center of Radiotherapy, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Udvarhelyi, Nora] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Orosz, Zsolt] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Kasler, Miklos] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
RP Zaka, Z (reprint author), National Institute of Oncology, Center of Radiotherapy, 1122 Budapest, Hungary.
EM zaka@oncol.hu
CR Chon BH, Loeffler JS, 2002, The effect of nonmalignant systemic disease on tolerance to radiation therapy. Oncologist 2:136–143
Cowie F, Jones R, 1999, Subcutaneous calcification as a late effect of orthovoltage chest wall irradiation. Clin Oncol 11:196–197
Steinert M, Gottlober P, Gall H, Peter RU, 2001, Subcutaneous calcification after radiotherapy. Hautarzt 52:518–521
Amin R, Hamilton-Wood C, Silver D, 2002, Subcutaneous calcification following chest wall and breast irradiation: a late complication. Br J Radiol 75:279–282
Carl UM, Hartman KA, 2002, Heterotopic calcification as a late radiation effect: report of 15 cases. Br J Radiol 75:460–463
Lewis VJ, Holt PJ, 2004, Sucutaneous calcification following high-dose radiotherapy. Br J Dermatol 150:1049–1050
Morris MM, Powell SN, 1997, Irradiation in the setting of collagen vascular disease: acute and late complications. J Clin Oncol 15:2728–2735
Gatti RA, 2001, The inherited basis of human radiosensitivity. Acta Oncol 40:702–711
McCuaig C, Marcoux D, Rasmussen JE, Werner MM, Gentner NE, 1993, Trichothiodystrophy associated with photosensitivity, gonadal failure, and striking osteosclerosis. J Am Acad Dermatol 28:820–826
Sator PG, Schmidt JB, Honigsmann H, 2003, Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis. J Am Acad Dermatol 48:352–358
DiGiovanna JJ, Robinson-Bostom L, 2003, Ichthyosis: etiology, diagnosis, and treatment. Am J Clin Dermatol 4:81–95
Fleckman P, Brumbaugh S, 2002, Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris. Exp Dermatol 11:327– 336
Lykkesfeldt G, Bennett P, Lykkesfeldt AE, Micic S, Rorth M, Skakkebaek NE, Svenstrup B, 1991, Testis cancer. Ichthyosis constitutes a significant risk factor. Cancer 67:730–734
Elbaum DJ, Kurz G, MacDuff M, 1995, Increased incidence of cutaneous carcinomas in patients with congenital ichthyosis. J Am Acad Dermatol 33:884–886
Kato N, Yasukawa K, Kimura K, Yoshida K, 2000, Anaplastic large-cell lymphoma associated with acquired ichthyosis. J Am Acad Dermatol 42:914–920
Kim KH, Kim JS, Piao YJ, Kim YC, Shur KB, Lee JH, Park JK, 2002, Keratitis, ichthyosis and deafness syndrome with development of multiple hair follicle tumours. Br J Dermatol 147:139–143
Krasagakis K, Ioannidou DJ, Stephanidou M, Manios A, Panayiotides JG, Tosca AD, 2003, Early development of multiple epithelial neoplasms in Netherton syndrome. Dermatology 207:182–184
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 485
EP 488
DI 10.1007/s12253-008-9062-8
PG 4
ER
PT J
AU Kojima, M
Kitamoto, Y
Shimizu, K
Matsuda, H
Masawa, N
AF Kojima, Masaru
Kitamoto, Yoshizumi
Shimizu, Kazuhiko
Matsuda, Hazuki
Masawa, Nobuhide
TI Tonsillar Lesions of Infectious Mononucleosis Resembling MALT Type Lymphoma. A Report of Two Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Infectious mononucleosis; Epstein–Barr virus; Tonsil; MALT type lymphoma; Immunohistochemistry
ID Infectious mononucleosis; Epstein–Barr virus; Tonsil; MALT type lymphoma; Immunohistochemistry
AB Infectious mononucleosis (IM) is an acute lymphoproliferative disorder that typically occurs in young patients and is usually caused by Epstein–Barr virus. We report here, two cases of tonsillar lesion of IM resembling marginal zone B-cell lymphoma mucosa-associated lymphoid tissue (MALT) type. The patients consisted of an 18-year-old Japanese woman and a 36-year-old Japanese man. Both patients presented with tonsillar mass. Histologically, in one case, the tonsil showed diffuse proliferation of medium-sized lymphocytes. The medium-sized lymphocytes had round or slightly indented nuclei with a small solitary nucleoli and abundant clear cytoplasm and somewhat resembled monocytoid B-cells. In the remaining one case, the lymphoid follicles had hyperplastic germinal centers with ill-defined borders surrounded by a sheet-like proliferation of polymorphous infiltration showing a marginal zone distribution pattern. On high-power field, the interfollicular area was diffusely infiltrated by a polymorphous infiltrate of medium-sized lymphocytes with angulated nuclei somewhat resembling centrocyte-like cells, immunoblasts, plasma cells, plasmacytoid cells and histiocytes with or without epithelioid cell feature. However, there were no CD43+ B-cells in either lesion. Moreover, the polytypic nature of the B-cells was demonstrated by immunohistochemistry or polymerase chain reaction. Although MALT type lymphoma rarely affected young adults, notably, a number of cases have been reported in the tonsil. The present two cases indicated that acute IM should be added to the differential diagnosis for MALT type lymphoma in young adults.
C1 [Kojima, Masaru] Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 617-1, Takabayashinishi-cho, 373-8550 Ohta, Japan.
[Kitamoto, Yoshizumi] Gunma Cancer Center Hospital, Department of RadiologyOhta, Japan.
[Shimizu, Kazuhiko] Ashikaga Red Cross Hospital, Department of Pathology and Clinical LaboratoriesAshikaga, Japan.
[Matsuda, Hazuki] Dokkyo Medical University School of Medicine, Department of Diagnostic and Anatomic PathologyMibu, Japan.
[Masawa, Nobuhide] Dokkyo Medical University School of Medicine, Department of Diagnostic and Anatomic PathologyMibu, Japan.
RP Kojima, M (reprint author), Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 373-8550 Ohta, Japan.
EM mkojima@gunma-cc.jp
CR Symmers WStC, 1992, Infectious mononucleosis. In: Henry K, Symmers WStC, eds, Thymus, lymph node, spleen and lymphatics. Systemic pathology, 3rd edn, vol7. Churchill Livingstone, Edinburgh, pp 432–437
Henle W, Henle GE, Horwiltz CA, 1974, Epstein–Barr virus specific diagnostic tests in infectious mononucleosis. Human Pathol 5:551–565
Childs CC, Parham DM, Berard CW, 1987, Infectious mononucleosis. The spectrum of morphologic changes simulating lymphoma in lymph node and tonsils. Am J Surg Pathol 11:122–132
Strickler JG, Fedeli F, Horwitz CA et al, 1993, Infectious mononucleosis in lymphoid tissue-histopathology, in situ hybridization and differential diagnosis. Arch Pathol Lab Med 117: 269–278
Wan JH, Trainor KJ, Brisco MJ et al, 1990, Monoclonality in B cell lymphoma detected in paraffin wax embedded sections using the polymerase chain reaction. J Clin Pathol 43:888–890
Isaacson PG, Spencer J, 1987, Malignant lymphoma of mucosaassociated lymphoid tissue. Histopathology 11:445–462
Feller AC, Diebold J, 2003, Histopathology of nodal and extranodal non-Hodgkin's lymphomas. Springer, Berlin
Wang T, Lasota J, Hanau CA et al, 1995, Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphoma but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferation is of diagnostic value. APMIS 103:655–662
Patsouris E, Noel H, Lennert K, 1990, Lymphoplasmacytic/ lymphoplasmacytoid immunocytoma with a high content of epithelioid cells. Histologic and immunohistochemical findings. Am J Surg Pathol 14:660–670
Kojima M, Nakamura S, Shimizu K et al, 2001, Marginal zone B cell lymphomas of Waldeyer’s ring. A report of two tonsillectomy cases resembling histomorphologic features of inflammatory lesions. Pathol Res Pract 197:781–784
Taddesse-Heath L, Pittaluga S, Sorbara L et al, 2003, Nodal marginal zone B-cell lymphoma in young adults. Am J Surg Pathol 27:522–531
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 489
EP 492
DI 10.1007/s12253-008-9033-0
PG 4
ER
PT J
AU Sagnak, L
Topaloglu, H
Gucuk, O
Unsal, H
Ersoy, H
AF Sagnak, Levent
Topaloglu, Hikmet
Gucuk, Osman
Unsal, Han
Ersoy, Hamit
TI Skip Metastase on the Left Neck Lymph Nodes of the Prostatic Adenocarcinoma with Neuroendocrine Differentiation and Accompanying Thyroid Micropapillary Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate neuroendocrine adenocarcinoma; Skip metastase; Thyroid papillary carcinoma
ID Prostate neuroendocrine adenocarcinoma; Skip metastase; Thyroid papillary carcinoma
AB We discuss here the thyroid micropapillary carcinoma that was detected incidentally when investigating the primary focus of the left neck multiple lymph node metastases occurring 8 months later in a patient of ours, whose pathological examination of radical prostatectomy and bilateral inguinal lymph node dissection was reported to be pT3N0 and whole body scanning for metastases, was negative.
C1 [Sagnak, Levent] Ministry of Health, Yildirim Beyazit Training Hospital, 3rd Urology Clinic, Angoraevleri, Altinbel Villalari, No: 38/A, 06800 Ankara, Turkey.
[Topaloglu, Hikmet] Ministry of Health, Yildirim Beyazit Training Hospital, 3rd Urology Clinic, Angoraevleri, Altinbel Villalari, No: 38/A, 06800 Ankara, Turkey.
[Gucuk, Osman] Ministry of Health, Yildirim Beyazit Training Hospital, 3rd Urology Clinic, Angoraevleri, Altinbel Villalari, No: 38/A, 06800 Ankara, Turkey.
[Unsal, Han] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Ersoy, Hamit] Ministry of Health, Yildirim Beyazit Training Hospital, 3rd Urology Clinic, Angoraevleri, Altinbel Villalari, No: 38/A, 06800 Ankara, Turkey.
RP Sagnak, L (reprint author), Ministry of Health, Yildirim Beyazit Training Hospital, 3rd Urology Clinic, 06800 Ankara, Turkey.
EM leventsagnak@gmail.com
CR Greenlee RT, Murray T, Bolden S, Wingo PA, 2000, Cancer statistics,2000. CA Cancer J Clin 50:7–33
Epstein JI, 2002, Pathology of prostatic neoplasia. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds, Campbell’s Urology, 8th edn, vol.4, chp 86. WB Saunders, Philadelphia, pp 3025–3037
Saitoh H, Yoshida K, Uchijima Y, Kobayashi N, Suwata J, Kamata S, 1990, Two different lymph node metastatic patterns of a prostatic cancer. Cancer 65(8):1843–1846
Wang HJ, Chiang PH, Peng JP, Yu TJ, 2004, Presentation of prostate carcinoma with cervical lymphadenopathy: report of three cases Med J 27(11):840–844
Copeland B, Clark JM, Sura A, Kilpatrick SE, Shockley W, Meredith S, 2001, Prostate carcinoma metastatic to the cervical lymph nodes: report of two cases and review of the literature. Am J Otolaryngol 22(6):420–423
Ozgur A, Ilker Y, Turkeri LN, 2003, Cervical lymph node enlargement on the right side as the initial manifestation of metastatic prostate cancer. Arch Esp Urol 56(7):859–861
Carleton J, van der Riet P, Dahm P, 2005, Metastatic prostate cancer presenting as an asymptomatic neck mass. Prostate Cancer Prostatic Dis 8(3):293–295
di Sant’Agnese PA, 1992, Neuroendocrine differantiation in human prostatic carcinoma. Human Pathol 23(3):287–296
di Sant’Agnese PA, 2000, Divergent neuroendocrine differentiation in prostatic carcinoma. Semin Diagn Pathol 17(2):149–161
Fernandes RC, Matsushita MM, Manuad T, Nascimento Saldiva PH, 2001, Prostate carcinoma with neuroendocrine differentiation: case report and literature review. Rev Hosp Clin Fac Med Sao Paulo 56(5):153–158
Bostwick DG, 1997, Neoplasms of the prostate. In: Bostwick DG, ed, Urologic Surgical Pathology. Mosby-Year Book, St.Louis
di Sant’Agnese PA, Cockett AT, 1996, Neuroendocrine differentiation in prostatic malignancy. Cancer 78(2):357–361
Ishida E, Nakamura M, Shimada K, Matsuyoshi S, Tada K, Okajima E, Fujimoto k, Konishi N, 2004, Autopsy case of prostate cancer with multiple endocrine neoplasia 2A. Pathol Int 54(12):918–923
Goulet-Salmon B, Berthe E, Franc S, Chanel S, Galateau-Salle F, Kottler M, Mahoudeau J, Reznik Y, 2004, Prostatic neuroendocrine tumor in multiple endocrine neoplasia type 2b. Endocrinol Invest 27, 6):570–573
Bayram F, Soyuer I, Atmaca H, Demirci D, Gokce C, Canoz O, Unluhizarci K, Kelestimur F, 2004, Prostatic adenocarcinoma metastasis in the thyroid gland. Endocrine Journal 51(4):445–448
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 493
EP 495
DI 10.1007/s12253-008-9029-9
PG 3
ER
PT J
AU Pina-Oviedo, S
Del Valle, L
Padilla-Longoria, R
Mendoza-Ramon, H
Ortiz-Hidalgo, C
AF Pina-Oviedo, Sergio
Del Valle, Luis
Padilla-Longoria, Rafael
Mendoza-Ramon, Hilda
Ortiz-Hidalgo, Carlos
TI Primary Adamantinoma of the Rib. Unusual Presentation for a Bone Neoplasm of Uncertain Origin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adamantinoma; Bone tumor; Bone epithelial neoplasm; Immunohistochemistry
ID Adamantinoma; Bone tumor; Bone epithelial neoplasm; Immunohistochemistry
AB Adamantinomas are rare, low-grade malignant intra-osseous tumors composed of epithelial and mesenchymal elements, which show a marked predilection for the tibia and fibula of young adult male patients. Although cases of adamantinoma located to the axial skeleton have been reported either as recurrent or metastatic disease, only two cases of primary adamantinoma located to the thoracic wall have been previously described. In this study we present the clinical, radiological and histopathological features of a 24-year-old male with a slow growing, solid-cystic, painful mass, located to the right 11th rib, which was morphological and immunohistochemically diagnosed as a primary classic adamantinoma. Radiological studies showed a multiloculated lesion with a solid component. The patient underwent a whole surgical resection of the lesion. Histologically, multiple foci of epithelial cells with basaloid and squamous components were found intermixed within a fibrous stromal tissue. Immunohistochemical analysis demonstrated expression of cytokeratins, EMA, vimentin and other epithelial markers. Primary affection of the rib is an unusual feature of classic adamantinomas.
C1 [Pina-Oviedo, Sergio] Universidad Panamericana, School of Medicine, Laboratory of Tissue and Cell BiologyMexico City, Mexico.
[Del Valle, Luis] Temple University, School of Medicine, Department of NeurosciencePhiladelphia, PA, USA.
[Padilla-Longoria, Rafael] The American British Cowdray Medical Center, Department of Surgical OncologyMexico City, Mexico.
[Mendoza-Ramon, Hilda] The American British Cowdray Medical Center, Department of Pathology, Calle Sur 132, No. 116. Colonia Las Americas, C.P. 01120 Mexico City, Mexico.
[Ortiz-Hidalgo, Carlos] Universidad Panamericana, School of Medicine, Laboratory of Tissue and Cell BiologyMexico City, Mexico.
RP Ortiz-Hidalgo, C (reprint author), Universidad Panamericana, School of Medicine, Laboratory of Tissue and Cell Biology, Mexico City, Mexico.
EM cortiz@abchospital.com
CR Hogendoorn PCW, Hashimoto H, 2002, Adamantinoma. In: Fletcher CDM, Unni KK, Mertens F. eds. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon, France pp. 332–334
Kahn LB, 2003, Adamantinoma, osteofibrous dysplasia and differentiated adamantinoma. Skelet Radiol 32:45–58
Maier C, 1900, Ein primares myelogenes platten epithelkarcinom der ulna. Beitr Klin Chir 26:553–556
Fischer B, 1913, Uber ein primares adamantinoma der tibia. Frankfurt Z Path 12:422–441
Bohndorf K, Nidecker A, Mathias K et al, 1992, The radiological findings in adamantinoma of the long tubular bones. Rofo 157:239–244
Putnam A, Yandow S, Coffin CM, 2003, Classic adamantinoma with osteofibrous dysplasia-like foci and secondary aneurismal bone cyst. Pediatr Dev Pathol 6:173–178
Weiss SW, Dorfman HD, 1977, Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes. Hum Pathol 8:141–153
Plump D, Haponik EF, Katz RS et al, 1986, Primary adamantinoma of rib: thoracic manifestations of a rare bone tumor. South Med J 79:352–355
Beppu H, Yamaguchi H, Yoshimura N et al, 1994, Adamantinoma of the rib metastasizing to the liver. Int Med 33:441–445
Czerniak B, Rojas-Corona RR, Dorfman HD, 1989, Morphologic diversity of long bone adamantinoma. The concept of differentiated, regressing, adamantinoma and its relationship to ostefibrous dysplasia. Cancer 64:2319–2334
Maki M, Athanasou N, 2004, Osteofibrous dysplasia and adamantinoma: correlation of proto-oncogene product and matrix protein expression. Hum Pathol 35:69–74
Bridge JA, Dembinski A, DeBoer J et al, 1994, Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma. Cancer 73:1746–1752
Kanamori M, Antonescu CR, Scott M et al, 2001, Extra copies of chromosomes 7, 8, 12, 19 and 21 are recurrent in adamantinomas. J Mol Diagn 3:16–21
Hazelbag HM, Fleuren JG, van den Broek LJ et al, 1993, Adamantinoma of the long bones: keratin subclass immunoreactivity pattern with reference to its histogenesis. Am J Surg Pathol 17:1225– 1233
Altini M, Coleman H, Doglioni C et al, 2000, Calretinin expression in ameloblastomas. Histopathology 37:27–32
Bovee JV, van der Broek LJ, de Boer WI et al, 1998, Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis. J Pathol 184: 24–30
Qureshi AA, Shott S, Mallin BA et al, 2000, Current trends in the management of adamantinoma of long bones. An international study. J Bone Joint Surg Am 82-A:1122–1131
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2008
VL 14
IS 4
BP 497
EP 502
DI 10.1007/s12253-008-9009-0
PG 6
ER
PT J
AU Sereno, M
De castro, J
Belda-Iniesta, C
Garcia-Cabezas, AM
Cejas, P
Casado, E
Barriuso, J
Feliu, J
Larrauri, J
AF Sereno, Maria
De castro, Javier
Belda-Iniesta, Cristobal
Garcia-Cabezas, Angel Miguel
Cejas, Paloma
Casado, Enrique
Barriuso, Jorge
Feliu, Jaime
Larrauri, Javier
TI EPO-R Expression Patterns in Resected Gastric Adenocarcinoma Followed by Adjuvant Chemoradiation Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Epo-R; adjuvant chemoradiation
ID Gastric cancer; Epo-R; adjuvant chemoradiation
AB The primary aim was to determine whether Epo-R immunohistochemical expression is related to disease free survival (DFS) in specimens of GC from patients who underwent adjuvant chemoradiation. Specimens of gastric adenocarcinomas obtained from 44 patients who had undergone curative gastrectomy and adjuvant treatment were investigated immunohistochemically expression of Epo-R. Three patterns for Epo-R staining were defined: Pattern A (secretory cells-like staining), Pattern B (parietallike staining) and Pattern C (chief-like staining). Median DFS was 38 months (CI 95%: 33–43) and 15 months (IC 95%: 3–27) in the pattern B and C, respectively, but it was not reached in the pattern A (p=0.06). Our findings suggest that there may be a relationship between Epo-R expression and DFS in the patients with GC resected.
C1 [Sereno, Maria] Infanta Sofia Hospital, Medical Oncology Division, San Sebastian de los ReyesMadrid, Spain.
[De castro, Javier] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Belda-Iniesta, Cristobal] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Garcia-Cabezas, Angel Miguel] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Cejas, Paloma] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Casado, Enrique] Infanta Sofia Hospital, Medical Oncology Division, San Sebastian de los ReyesMadrid, Spain.
[Barriuso, Jorge] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Feliu, Jaime] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
[Larrauri, Javier] University Hospital La Paz, Medical Oncology DivisionMadrid, Spain.
RP Sereno, M (reprint author), Infanta Sofia Hospital, Medical Oncology Division, Madrid, Spain.
EM mariasereno@yahoo.es
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Mohyeldin A, Lu H, Dalgard C, Stephen Y, Noam C, Acs G, Verma A, 2005, Erythropoetin signaling promotes invasiveness of human head and neck squamous cell carcinoma. Neoplasia 7:537–543
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Ribatti D, Marzullo A, Nico E, Crivellato E, Ria R, 2003, Erythropoeitin as an angiogenic factor in gastric carcinoma. Histopathology 42:246–50
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Lugli A, Spichtin H, Maurer R, Mirlacher M, Kiefer J, Huusko P, Azorsa D, Terracciano L, Sauter G, Kallioniemi OP, Mousses S, Tornillo L, 2005, Erb-B2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers. Clin Cancer Res 11:6450–6458
Gomes LI, Esteves GH, Carvalho AF, Cristo EB, Hirata R Jr, Martins WK, Marques SM, Camargo LP, Brentani H, Pelosof A, Zitron C, Sallum RA, Montagnini A, Soares FA, Neves EJ, Reis LF, 2005, Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism. Cancer Res 65:7127–7136
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Elliott S, Busse L, Bass MB, Lu H, Sarosi I, Sinclair AM, Spahr C, Um M, Van G, Begley CG, 2006, Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 107:1892–1895
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 1
EP 10
DI 10.1007/s12253-008-9118-9
PG 10
ER
PT J
AU Barbanis, S
Ioannou, M
Kouvaras, E
Karasavvidou, F
Nakou, M
Papamichali, R
Koukoulis, G
AF Barbanis, Sotirios
Ioannou, Maria
Kouvaras, Evangelos
Karasavvidou, Foteini
Nakou, Marianna
Papamichali, Roidoula
Koukoulis, George
TI INCENP (Inner Centromere Protein) is Overexpressed in High Grade Non-Hodgkin B-cell Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Inner centromere protein (INCENP); MIB-1; Lymphoma; Aneuploidy; Immunohistochemistry
ID Inner centromere protein (INCENP); MIB-1; Lymphoma; Aneuploidy; Immunohistochemistry
AB Inner centromere protein (INCENP) is a member of the Chromosomal Passenger Complex (CPC), which is a four member protein complex essential for proper completion of mitosis and cell division (cytokinesis). Inappropriate chromosomal segregation and cytokinesis due to deregulated expression of chromosome passenger proteins may lead to aneuploidy and cancer including lymphomas. According to our knowledge this is the first study investigating immunohistochemical expression of INCENP in lymphoma cases and cancer tissues in general. Our purpose was to characterize the expression of INCENP in cases of non-Hodgkin B-cell lymphomas, to compare the immunoreactivity between low and high grades and to evaluate the correlation between INCENP and MIB-1 labeling indices. We examined INCENP and MIB-1 immunoreactivity in paraffin sections of 55 samples of non-Hodgkin B-cell lymphomas, obtained from 55 patients, 31 men and 24 women. Thirty were of high grade and 25 were of low grade. Our results showed significantly higher nuclear immunohistochemical expression of INCENP in high grade B-cell lymphomas versus low grade ones. Also INCENP expression was significantly correlated with MIB-1 labeling index. Taken together our results point to a possible association between increased INCENP immunostaining and B-cell lymphoma aggressiveness and also stress the need for further investigating the expression of INCENP and other mitotic regulatory proteins in lymphomas and other malignant neoplasms.
C1 [Barbanis, Sotirios] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Ioannou, Maria] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Kouvaras, Evangelos] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Karasavvidou, Foteini] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Nakou, Marianna] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Papamichali, Roidoula] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
[Koukoulis, George] University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Thessaly, Greece.
RP Barbanis, S (reprint author), University of Thessaly, Medical School, Department of Pathology, 411 10 Larissa, Greece.
EM sbarbanis@yahoo.gr
CR Ruchaud S, Carmena M, Earnshaw WC, 2007, Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8:798–812
Vader G, Medema RH, Lens SM, 2006, The chromosomal passenger complex: guiding Aurora-B through mitosis. J Cell Biol 173:833–837
Klein UR, Nigg EA, Gruneberg U, 2006, Centromere targeting of the chromosomal passenger complex requires a ternary subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP. Mol Biol Cell 17:2547–2558
Cooke CA, Heck MM, Earnshaw WC, 1987, The inner centromere protein, INCENP, antigens: movement from inner centromere to midbody during mitosis. J Cell Biol 105:2053–2067
Sessa F, Mapelli M, Ciferri C et al, 2005, Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell 18:379–391
Carmena M, Earnshaw WC, 2006, INCENP at the kinase crossroads. Nat Cell Biol 8:110–111
Adams RR, Eckley DM, Vagnarelli P et al, 2001, Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Chromosoma 110:65–74
Cutts SM, Fowler KJ, Kile BT et al, 1999, Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene, Incenp)-disrupted mice. Hum Mol Genet 8:1145–1155
Nguyen HG, Ravid K, 2006, Tetraploidy/aneuploidy and stem cells in cancer promotion: the role of chromosome passenger proteins. J Cell Physiol 208:12–22
Greaves S, 2001, A roar for INCENP. Nat Cell Biol 3:E14
Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC, 2001, INCENP is required for proper targeting of survivin to the centromeres and the anaphase spindle during mitosis. Curr Biol 11:886–890
Gerlach U, Kayser G, Walch A et al, 2006, Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer. J Pathol 208:462–472
Jaffe ES, Harris NL, Stein H, Vardiman JW, 2001, Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumours. IARC, Lyon
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Altieri DC, 2003, Survivin in apoptosis control and cell cycle regulation in cancer. Prog Cell Cycle Res 5:447–452
Mainou-Fowler T, Overman LM, Dignum H et al, 2008, A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2. Int J Oncol 32:59–68
Cong XL, Han ZC, 2004, Survivin and leukaemia. Int J Hematol 80:232–238
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Li F, 2005, Role of survivin and its splice variants in tumorigenesis. Br J Cancer 92:212–216
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Sorrentino R, Libertini S, Pallante Pl et al, 2005, Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 90:928–935
Sistayanarain A, Tsuneyama K, Zheng H et al, 2006, Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma. Anticancer Res 26:585–593
Chieffi P, Cozzolino L, Kisslinger A et al, 2006, Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate 66:326–333
Chang JL, Chen TH, Wang CF et al, 2006, Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer. Exp Cell Res 312:962–973
Miller TP, Grogan TM, Dahlberg S et al, 1994, Prognostic significance of the Ki-67-assosiated proliferative antigen in aggressive non-Hodgkin’s lymphomas: a prospective Southwest Oncology Group trial. Blood 83:1460–1466
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Lehman NL, Tibshirani R, Hsu JY et al, 2007, Oncogenic regulators and substrates of the anaphase promoting complex/ cyclosome are frequently overexpressed in malignant tumors. Am J Pathol 170:1793–1805
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 11
EP 17
DI 10.1007/s12253-008-9094-0
PG 7
ER
PT J
AU Bica, GC
de Moura da Silva, LL
Toscani, VN
da Cruz, BMI
Sa, G
Graudenz, SM
Zettler, GC
AF Bica, Giuliano Claudia
de Moura da Silva, Leiria Leonardo
Toscani, Vieira Nadima
da Cruz, Beatrice Manica Ivana
Sa, Gustavo
Graudenz, Silveira Marcia
Zettler, Galleano Claudio
TI MnSOD Gene Polymorphism Association with Steroid-Dependent Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MnSOD polymorphism; Male breast cancer; Female breast cancer; Prostate cancer; Steroid metabolism; Oxidative stress
ID MnSOD polymorphism; Male breast cancer; Female breast cancer; Prostate cancer; Steroid metabolism; Oxidative stress
AB Oxidative stress enhances carcinogenesis due to DNA damage. Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism has been recently associated with breast and prostate cancer. The role of oxidative stress in male breast cancer is poorly investigated due to the low prevalence of this neoplasia. We studied the relationship between prostate cancer (PC), male (MBC) and female breast cancer (FBC) and this polymorphism in a case–control study. Human genetic polymorphism Val16Ala of MnSOD was obtained from blood and paraffin-embedded tumor samples. The polymorphism was determined in 11 cases of MBC, 51 cases of PC, 89 cases of FBC and 372 age-adjusted healthy controls by polymerase chain reaction–restriction fragment length polymorphism techniques using restriction enzyme Hae III. Chi-square or Fisher test were used to compare the MnSOD frequency distribution. The observed genotypic frequencies of all samples were AA=9.6% (n=50), VV=25.4% (n=133) and AV=64% (n=340), all at Hardy–Weinberg equilibrium. Breast and prostate cancer risk was elevated in male and female patients with the Ala/Ala genotype compared to controls (p=0.006, odds ratio=2.5, 95% confidence interval 1.393–4.541). Even though the frequency of the Ala allele was low (9.6%) in the studied population, these data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk both in males and females and also brings new information on the role of this polymorphism in prostate cancer. This is the first study which provides some evidence that genetic polymorphism in the MnSOD gene may be associated with an increased risk of male breast cancer. Studies with a larger sample size are needed to confirm the findings.
C1 [Bica, Giuliano Claudia] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.
[de Moura da Silva, Leiria Leonardo] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.
[Toscani, Vieira Nadima] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.
[da Cruz, Beatrice Manica Ivana] Universidade Federal de Santa MariaSanta Maria, RS, Brazil.
[Sa, Gustavo] Pontificia Universidade Catolica do Rio Grande do SulPorto Alegre, RS, Brazil.
[Graudenz, Silveira Marcia] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.
[Zettler, Galleano Claudio] Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.
RP Bica, GC (reprint author), Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, 90050-170 Porto Alegre, Brazil.
EM bicaclaudia@hotmail.com
CR Martindale JL, Holbrook NJ, 2002, Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192:1–15
Suh YA, Arnold RS, Lassegue B et al, 1999, Cell transformation by the superoxide-generating oxidase Mox1. Nature 401:79–82
Arbiser JL, Petros J, Klafter R et al, 2002, Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc Natl Acad Sci U S A 99:715–720
Schwartz JL, Antoniades DZ, Zhao S, 1993, Molecular and biochemical reprogramming of oncogenesis through the activity of prooxidants and antioxidants. Ann NY Acad Sci 686: 262–278
Ross RK, Pike MC, Coetzee GA et al, 1998, Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res 58:4497–4504
Sutton A, Khoury H, Prip-Buus C, Cepanec C et al, 2003, The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics 13:145–157
Mitrunen K, Sillanpaa P, Kataja V et al, 2001, Association between manganese superoxide dismutase, MnSOD, gene polymorphism and breast cancer risk. Carcinogenesis 22:827–829
Millikan RC, Player J, de Cotret AR et al, 2004, Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case–control study of African Americans and whites. Breast Cancer Res 6:R264–274
Taufer M, Peres A, de Andrade VM et al, 2005, Is the Val16Ala manganese superoxide dismutase polymorphism associated with the aging process. J Gerontol A Biol Sci Med Sci 60:432–438
Woodson K, Tangrea JA, Lehman TA et al, 2003, Manganese superoxide dismutase, MnSOD, polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study, Finland). Cancer Causes Control 14:513–518
Wang LI, Neuberg D, Christiani DC, 2004, Asbestos exposure, manganese superoxide dismutase, MnSOD, genotype, and lung cancer risk. J Occup Environ Med 46:556–564
Stoehlmacher J, Ingles SA, Park DJ et al, 2002, The -9Ala/-9Val polymorphism in the mitochondrial targeting sequence of the manganese superoxide dismutase gene, MnSOD, is associated with age among Hispanics with colorectal carcinoma. Oncol Rep 9:235–238
Hung RJ, Boffetta P, Brennan P et al, 2004, Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis 25:973–978
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Cavalieri E, Frenkel K, Liehr JG et al, 2000, Estrogens as endogenous genotoxic agents–DNA adducts and mutations. J Natl Cancer Inst Monogr 27:75–93
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Egan KM, Thompson PA, Titus-Ernstoff L et al, 2003, MnSOD polymorphism and breast cancer in a population-based case– control study. Cancer Lett 199:27–33
Bhat HK, Calaf G, Hei TK et al, 2003, Critical role of oxidative stress in estrogen-induced carcinogenesis. Proc Natl Acad Sci U S A 100:3913–3918
Patel MM, Bhat HK, 2004, Differential oxidant potential of carcinogenic and weakly carcinogenic estrogens: involvement of metabolic activation and cytochrome P450. J Biochem Mol Toxicol 18:37–42
Hong CC, Tang BK, Rao V et al, 2004, Cytochrome P450 1A2, CYP1A2, activity, mammographic density, and oxidative stress: a cross-sectional study. Breast Cancer Res 6:R338–R351
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 19
EP 24
DI 10.1007/s12253-008-9064-6
PG 6
ER
PT J
AU Ioannou, GM
Stathakis, E
Lazaris, CA
Papathomas, Th
Tsiambas, E
Koukoulis, KG
AF Ioannou, G Maria
Stathakis, Efstathios
Lazaris, C Andreas
Papathomas, Thomas
Tsiambas, Evangelos
Koukoulis, K George
TI Immunohistochemical Evaluation of 95 Bone Marrow Reactive Plasmacytoses
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD56; Cyclin D1; Immunohistology; Bone marrow biopsies; Reactive plasmacytosis; Plasma cell myeloma
ID CD56; Cyclin D1; Immunohistology; Bone marrow biopsies; Reactive plasmacytosis; Plasma cell myeloma
AB We histologically and immunohistochemically studied 95 bone marrow (BM) reactive plasmacytoses. Ten biopsies from plasma cell myeloma (PCM) patients served as a control group. In addition, we studied 10 monoclonal gammopathy of undetermined significance (MGUS) cases. Histologically, plasmacytosis varied between 5% and 25% with an interstitial pattern of plasma cell (PC) distribution being characteristically displayed. Immunohistochemically, we did not find any CD56/NCAM nor cyclin D1 expression in all biopsies (95 of 95, 100%), not even a weak, doubtful one; PCs were all polyclonal and CD138 positive. On the contrary, myeloma-associated PCs showed monoclonality for .- or 1- light chain and strong CD56/NCAM immunoreactivity (8 of 10, 80%); four of them were cyclin D1 positive. Osteoblasts exhibited similar CD56/NCAM expression in both groups. Our data confirm the diagnostic utility of CD56/NCAM in the phenotypic characterization of polyclonal plasma cells, suggesting an important role of this particular immunomarker in the BM trephine study of polyclonal versus neoplastic plasmacytic infiltrations.
C1 [Ioannou, G Maria] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Stathakis, Efstathios] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Lazaris, C Andreas] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Papathomas, Thomas] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Tsiambas, Evangelos] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Koukoulis, K George] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
RP Papathomas, Th (reprint author), University of Thessaly, Medical School, Department of Pathology, Larissa, Greece.
EM thomaspapathomas@yahoo.gr
CR Bain BJ, Clark DM, Lampert IA, Wilkins BS, 2001, Bone marrow pathology. Blackwell Science, Oxford
Hyun BK, Kwa D, Gabaldon H, Ashton JK, 1976, Reactive plasmacytic lesions of the bone marrow. Am J Clin Pathol 65:921–928
Wei A, Juneja S, 2003, Bone marrow immunohistology of plasma cell neoplasms. J Clin Pathol 56:406–411
Grogan TM, Van Camp B, Kyle RA, Muller-Hermelink HK, Harris NL, 2001, Plasma cell neoplasms. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds, World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 142–156
Dick FR, 2002, Chronic lymphoproliferative disorders, immunoproliferative disorders, and malignant lymphoma. In: McClatchey KD, Weinberg RW, Reter RE, Foley T, eds, Clinical laboratory medicine. Lippincott Williams & Wilkins, Philadelphia, pp 923–963
Ely SA, Knowles DM, 2002, Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation. Am J Pathol 160: 1293–1299
Pellat-Deceunynck C, Barille S, Jego G et al, 1998, The absence of CD56, NCAM, on malignant plasma cells is a hallmark of plasma cell leukemia and of a special subset of multiple myeloma. Leukemia 12:1977–1982
Rawstron A, Barrans S, Blythe D et al, 1999, Distribution of myeloma plasma cells in peripheral blood and bone marrow correlates with CD56 expression. Br J Haematol 104:138–143
Pellat-Deceunynck C, Barille S, Puthier D et al, 1995, Adhesion molecules on human myeloma cells: significant changes in expression related to malignancy, tumor spreading, and immortalization. Cancer Res 55:3647–3653
Dahl IM, Rasmussen T, Kauric G, Husebekk A, 2002, Differential expression of CD56 and CD44 in the evolution of the extramedullary myeloma. Br J Haematol 116:273–277
Sahara N, Takeshita A, Shigeno K et al, 2002, Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma. Br J Haematol 117:882–885
Hedvat CV, Comenzo RL, Teruya-Feldstein J et al, 2003, Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma. Br J Haematol 122:728–744
Kremer M, Ott G, Nathrath M et al, 2005, Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis. J Pathol 205:92–101
Sahara N, Takeshita A, 2004, Prognostic significance of surface markers expressed in multiple myeloma: CD56 and other antigens. Leuk Lymphoma 45:61–65
Van Camp B, Durie BG, Spier C et al, 1990, Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56, NKH-1; Leu-19). Blood 76:377–382
Martin P, Santon A, Bellas C, 2004, Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis. Histopathology 44:375–380
Dunphy CH, Nies MK, Gabriel DA, 2007, Correlation of plasma cell percentages by CD138 immunohistochemistry, cyclin D1 status, and CD56 expression with clinical parameters and overall survival in plasma cell myeloma. Appl Immunohistochem Mol Morphol 15:248–254
Fend F, Kremer M, 2007, Diagnosis and classification of malignant lymphoma and related entities in the bone marrow trephine biopsy. Pathobiology 74:133–143
Kremer M, Quintanilla-Martinez L, Nahrig J, Von Schilling C, Fend F, 2005, Immunohistochemistry in bone marrow pathology: a useful adjunct for morphologic diagnosis. Virchows Arch 447:920–937
Sukpanichnant S, Cousar JB, Leelasiri A, Graber SE, Greer JP, Collins RD, 1994, Diagnostic criteria and histologic grading in multiple myeloma: histologic and immunohistologic analysis of 176 cases with clinical correlation. Hum Pathol 25:308–318
Cotelingam JD, 2003, Bone marrow biopsy: interpretive guidelines for the surgical pathologist. Adv Anat Pathol 10:8–26
Brunning RD, 2004, Bone Marrow. In: Rosai J, Houston M, eds, Rosai and Ackerman’s surgical pathology. Mosby, St. Louis, pp 2099–2108
Bataille R, Jego G, Robillard N et al, 2006, The phenotype of normal, reactive and malignant plasma cells. Identification of “many and multiple myelomas” and of new targets for myeloma therapy. Haematologica 91:1234–1240
Sezer O, Heider U, Zavrski I, Possinger K, 2001, Differentiation of monoclonal gammopathy of undetermined significance and multiple myeloma using flow cytometric characteristics of plasma cells. Haematologica 86:837–843
Naresh KN, Lampert I, Hasserjian R et al, 2006, Optimal processing of bone marrow trephine biopsy: the Hammersmith Protocol. J Clin Pathol 59:903–911
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 25
EP 29
DI 10.1007/s12253-008-9069-1
PG 5
ER
PT J
AU Qiao, L
Wang, Y
Pang, R
Wang, J
Dai, Y
Ma, J
Gu, Q
Li, Z
Zhang, Y
Zou, B
Lan, YH
Wong, CYB
AF Qiao, Liang
Wang, Yan
Pang, Roberta
Wang, Jide
Dai, Yun
Ma, Juan
Gu, Qing
Li, Zesong
Zhang, Yusheng
Zou, Bing
Lan, Y H
Wong, C Y Benjamin
TI Oncogene Functions of FHL2 Are Independent from NF-κBIα in Gastrointestinal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FHL2; NF-κB; NF-κBIα; Interaction; Gastric cancer; Colon cancer
ID FHL2; NF-κB; NF-κBIα; Interaction; Gastric cancer; Colon cancer
AB Four and a half of LIM-only protein 2 (FHL2) is an adaptor protein that can interact with many transcription factors and thus plays a variety of biological functions. Previous studies by our group have demonstrated that suppression of FHL2 was capable of inducing tumor cell differentiation, and inhibiting the growth of experimental gastric and colon cancers. Therefore, FHL2 appears to function as an oncogene. In order to further explore the mechanisms of how FHL2 is involved in tumorigenesis, we attempted to test whether FHL2 has any direct association with nuclear factor (NF-κB), the most important transcription factor involved in apoptosis, inflammation, and carcinogenesis. Using an Yeast Two Hybrid (Y2H) screening system, we have shown that FHL2 may have an interaction with NF-κBIα, the coding gene for IκBα which is the most potent endogenous inhibitor for NF-κB activation. However, subsequent studies using co-immunoprecipitation and colocalization failed to confirm the Y2H finding. Downregulation of FHL2 by FHL2-siRNA down-regulated the expression of NF-κB p65. We therefore concluded that under the physiological condition, FHL2 may activate NF-κB pathway, even though such an activation may not be mediated by a direct binding of FHL2 to NF-κB inhibitor protein IκB.
C1 [Qiao, Liang] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Wang, Yan] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Pang, Roberta] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Wang, Jide] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Dai, Yun] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Ma, Juan] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Gu, Qing] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Li, Zesong] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Zhang, Yusheng] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Zou, Bing] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Lan, Y H] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
[Wong, C Y Benjamin] Queen Mary Hospital, University of Hong Kong, Department of MedicineHong Kong, Hong Kong.
RP Wong, CYB (reprint author), Queen Mary Hospital, University of Hong Kong, Department of Medicine, Hong Kong, Hong Kong.
EM bcywong@hku.hk
CR Chan KK, Tsui SK, Lee SM, Luk SC, Liew CC, Fung KP, Waye MM, Lee CY, 1998, Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart. Gene 210:345–350
Genini M, Schwalbe P, Scholl FA, Remppis A, Mattei MG, Schafer BW, 1997, Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma. DNA Cell Biol 16:433–442
Scholl FA, McLoughlin P, Ehler E, de Giovanni C, Schafer BW, 2000, DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis. J Cell Biol 151:495–506
Kinoshita M, Nakagawa T, Shimizu A, Katsuoka Y, 2005, Differently regulated androgen receptor transcriptional complex in prostate cancer compared with normal prostate. Int J Urol 12:390–397
Gabriel B, Mildenberger S, Weisser CW, Metzger E, Gitsch G, Schule R, Muller JM, 2004, Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and both are overexpressed in epithelial ovarian cancer. Anticancer Res 24:921–927
Wang J, Yang Y, Xia HH, Gu Q, Lin MC, Jiang B, Peng Y, Li G, An X, Zhang Y, Zhuang Z, Zhang Z, Kung HF, Wong BC, 2007, Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis. Gastroenterology 132:1066–1076
Wei Y, Renard CA, Labalette C,Wu Y, Levy L, Neuveut C, Prieur X, Flajolet M, Prigent S, Buendia MA, 2003, Identification of the LIM protein FHL2 as a coactivator of b-catenin. J Biol Chem 278:5188– 5194
Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q, 2003, BRCA1 interacts with FHL2 and enhances FHL2 transactivation function. FEBS Lett 553:183–189
Martin BT, Kleiber K,Wixler V, Raab M, Zimmer B, Kaufmann M, Strebhardt K, 2007, FHL2 regulates cell cycle-dependent and doxorubicin-induced p21Cip1/Waf1 expression in breast cancer cells. Cell Cycle 6:1779–1788
Muller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schule R, 2000, FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J 19:359–369
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Gao J, Pfeifer D, He LJ, Qiao F, Zhang Z, Arbman G, Wang ZL, Jia CR, Carstensen J, Sun XF, 2007, Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol 42:345– 350
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 31
EP 36
DI 10.1007/s12253-008-9085-1
PG 6
ER
PT J
AU Dehaghani, SA
Rad, RN
Fattahi, JM
Khadang, B
Kashef, AM
Sarraf, Z
Ghaderi, A
AF Dehaghani, Samsami Alamtaj
Rad, Rahimi Neda
Fattahi, Javad Mohammad
Khadang, Baharak
Kashef, Amin Mohammad
Sarraf, Zahra
Ghaderi, Abbas
TI Investigation of Soluble HER2 and Transforming Growth Factor Beta-1 Serum Levels in Gestational Trophoblastic Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER2; TGF-β1; Gestational trophoblastic disease
ID HER2; TGF-β1; Gestational trophoblastic disease
AB HER2/neu and TGF-β1 are over-expressed in various types of malignancies. It appears that they play an important role in the biologic behavior of tumors and have prognostic value. Gestational tropoblastic diseases (GTDs) comprise of a heterogeneous group characterized by abnormally proliferating trophoblastic tissues, ranging from benign to malignant. The objective of this study was to measure and compare the serum levels of s-HER2 and TGF-β between patients with GTDs and pregnant and nonpregnant controls. Serum levels of s-HER2 and TGF-β1 were determined by ELISA method in 95 GTD patients (55 complete moles, 32 persistent moles, and 8 choriocarcinoma), 30 normal pregnant controls, and 22 normal nonpregnant controls. Mean serum level of s-HER2 did not differ significantly between patients and controls. TGF-β1 serum level was significantly higher in GTD patients (20.29±10.68 pg/ml with 95% confidence interval (CI) of 18.10–22.48 pg/ml) compared with pregnant controls (10.26±11.84 pg/ml with 95% CI of 5.75–14.76 pg/ml) and non-pregnant controls (7.27±9.61 pg/ml with 95% CI of 3.01–11.53 pg/ml) (P<0.001). Our findings suggest that TGF-β1 serum levels in GTD patients may represent a potential prognostic marker. Further investigations with larger sample size and more frequent sampling are required to elucidate this issue.
C1 [Dehaghani, Samsami Alamtaj] Shiraz University of Medical Sciences, Hafez hospital, Department of Obstetric and Gynecology, 71345-1798 Shiraz, Iran.
[Rad, Rahimi Neda] Shiraz University of Medical Sciences, Hafez hospital, Department of Obstetric and Gynecology, 71345-1798 Shiraz, Iran.
[Fattahi, Javad Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Khadang, Baharak] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Kashef, Amin Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Sarraf, Zahra] Shiraz University of Medical Sciences, Hafez hospital, Department of Obstetric and Gynecology, 71345-1798 Shiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Dehaghani, SA (reprint author), Shiraz University of Medical Sciences, Hafez hospital, Department of Obstetric and Gynecology, 71345-1798 Shiraz, Iran.
EM samsamia@sums.ac.ir
CR Genest DR, Berkowitz RS, Fisher RA, Newlands ES, Fehr M, 2003, Gestational trophoblastic disease. In: Tavassoli FA, Devilee P, eds, World Health Organization Classification of Tumors. Pathology and Genetics. Tumors of the Breast and Female Genital Organs. IARC, Lyon, pp 250–254
Sivanesaratnam V, 2003, Management of gestational trophoblastic disease in developing countries. Best Pract Res Clin Obstet Gynaecol 17:925–42
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 37
EP 40
DI 10.1007/s12253-008-9115-z
PG 4
ER
PT J
AU Bori, R
Cserni, G
AF Bori, Rita
Cserni, Gabor
TI Basal Phenotype in Breast Carcinoma Occurring in Women Aged 35 or Younger
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal-like phenotype; BRCA1 mutation; Breast cancer in young women
ID Basal-like phenotype; BRCA1 mutation; Breast cancer in young women
AB Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.
C1 [Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
RP Bori, R (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, 6000 Kecskemet, Hungary.
EM boririta@hotmail.com
CR Fernandopulle SM, Cher-Siangang P, Tan PH, 2006, Breast carcinoma in women 35 years and younger: a pathological study. Pathology 38:219–222
Figueiredo JC, Ennis M, Knight JA et al, 2007, Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study. Breast Cancer Res Treat 105:69–80
Armes JE, Egan AJ, Southey MC et al, 1998, The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study. Cancer 83:2335–2345
Bennett IC, Freitas R Jr, Fentiman IS, 1991, Diagnosis of breast cancer in young women. Aust N Z J Surg 61:284–289
Tai P, Cserni G, Van de Steene J et al, 2005, Modeling the effect of age in T1-T2 breast cancer using the SEER database. BMC Cancer 5:130., DOI 10.1186/1471-2407-5-130
Trecate G, Vergnaghi D, Manoukian S et al, 2006, MRI in the early detection of breast cancer in women with high genetic risk. Tumori 92:517–523
Golshan M, Miron A, Nixon AJ, 2006, The prevalence of germline BRCA1 and BRCA2 mutations in young women with breast cancer undergoing breast-conservation therapy. Am J Surg 192:58–62
Lubinski J, Gorski B, Huzarski T et al, 2006, BRCA1-positive breast cancers in young women from Poland. Breast Cancer Res Treat 99:71–76
Loizidou M, Marcou Y, Anastasiadou V et al, 2007, Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus. Clin Genet 71:165–170
Foulkes WD, Brunet JS, Stefansson IM et al, 2004, The prognostic implication of the basal-like, cyclin E high/p27 low/ p53+/glomeruloid-microvascular-proliferation+, phenotype of BRCA1-related breast cancer. Cancer Res 64:830–835
Foulkes WD, Metcalfe K, Sun P et al, 2004, Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. Clin Cancer Res 10:2029– 2034
Laakso M, Loman N, Borg A et al, 2005, Cytokeratin 5/14- positive breast cancer: true basal phenotype confined to BRCA1 tumors. Mod Pathol 18:1321–1328
Lakhani SR, Reis-Filho JS, Fulford L et al, 2005, Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11:5175–5180
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Foulkes WD, Stefansson IM, Chappuis PO et al, 2003, Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485
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Reis-Filho JS, Milanezi F, Steele D et al, 2006, Metaplastic breast carcinomas are basal-like tumours. Histopathology 49:10–21
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Banerjee S, Reis-Filho JS, Ashley S et al, 2006, Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol 59:729–735
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 41
EP 45
DI 10.1007/s12253-008-9090-4
PG 5
ER
PT J
AU Csete, B
Lengyel, Zs
Kadar, Zs
Battyani, Z
AF Csete, Bela
Lengyel, Zsuzsanna
Kadar, Zsolt
Battyani, Zita
TI Poly(Adenosine Diphosphate-Ribose) Polymerase-1 Expression in Cutaneous Malignant Melanomas as a New Molecular Marker of Aggressive Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cutaneous malignant melanoma; Immunohistochemistry; Poly(ADP-ribose) polymerase-1
ID Cutaneous malignant melanoma; Immunohistochemistry; Poly(ADP-ribose) polymerase-1
AB Poly(adenosine diphosphate-ribose) polymerases (PARPs) are a family of enzymes, which catalyses poly (ADP-ribosyl)ation of DNA-binding proteins and directly involved in genomic stability, DNA repair, and apoptosis. In this study, we evaluated the immunomorphology of PARP-1 in melanoma and its prognostic importance. We studied PARP-1 expression by immunohistochemistry in a selected series of 54 primary cutaneous malignant melanoma (CMM). The findings of the present study suggest that the neoplastic progression toward the invasive (both horizontal and vertical) growth phase of CMM cells is characterized by the loss of cleavage of PARP-1, probably signaling an imbalance of the apoptotic process in these cells and leading to further gain to aggression. Over-expression of full-length PARP-1 was correlated with recurrence and/or progression of the disease and so act as a promising new biological marker of CMM. Our study represents the evidence of a direct correlation between the PARP-1-mediated apoptotic process and the biologic behavior of CMM.
C1 [Csete, Bela] University of Pecs, Department of Dermatology, Venereology and Oncodermatology, 20. Kodaly Z. u.Pecs, Hungary.
[Lengyel, Zsuzsanna] University of Pecs, Department of Dermatology, Venereology and Oncodermatology, 20. Kodaly Z. u.Pecs, Hungary.
[Kadar, Zsolt] University of Pecs, Department of Dermatology, Venereology and Oncodermatology, 20. Kodaly Z. u.Pecs, Hungary.
[Battyani, Zita] University of Pecs, Department of Dermatology, Venereology and Oncodermatology, 20. Kodaly Z. u.Pecs, Hungary.
RP Csete, B (reprint author), University of Pecs, Department of Dermatology, Venereology and Oncodermatology, Pecs, Hungary.
EM benig@freemail.hu
CR Ame JC, Spenkehauer C, de Murcia G, 2004, The PARP superfamily. Bioessays 26:882–893
Wang X, Ohnishi K, Takahasi A et al, 1998, Poly(ADP-ribosyl, ation is required for p53-dependent signal transduction induced by radiation. Oncogene 17:2819–2825
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Vodenicharov MD, Ghodgaonkar MM, Halappanavar SS et al, 2005, Mechanism of early biphasic activation of poly(ADPribose, polymerase-1 in response to ultraviolet B radiation. J Cell Sci 118:589–599
Staibano S, Pepe S, Muzio L et al, 2005, Poly(adenosine diphosphate-ribose, polymerase-1 expression in malignant melanomas from photoexposed areas of the head and neck region. Human Pathol 36:724–731
Balch CM, Buzaid AC, Atkins MB et al, 2001, Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648
Masutani M, Nakagama H, Sugimura T, 2005, Poly(ADP-ribosyl, ation in relation to cancer and autoimmune disease. Cell Mol Life Sci 62:769–783
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Vaculova A, Hofmanova J, Soucek K et al, 2002, Tumor necrosis factor-alpha induces apoptosis associated with poly(ADP-ribose, polymerase cleavage in HT-29 colon cancer cells. Anticancer Res 22:1635–1639
Shyong EQ, Lu Y, Lazinsky A et al, 2002, Effects of the isoflavone 4V,5,7-trihydroxyisoflavone, genistein, on psoralen plus ultraviolet A radiation, PUVA)-induced photodamage. Carcinogenesis 23:317–321
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 47
EP 53
DI 10.1007/s12253-008-9086-0
PG 7
ER
PT J
AU Krenacs, T
Zsakovics, I
Diczhazi, Cs
Ficsor, L
Varga, SV
Molnar, B
AF Krenacs, Tibor
Zsakovics, Ivett
Diczhazi, Csaba
Ficsor, Levente
Varga, S V
Molnar, Bela
TI The Potential of Digital Microscopy in Breast Pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Digital microscopy; Breast pathology; Teleconsultation; Proficiency testing; Biomarker quantitation
ID Digital microscopy; Breast pathology; Teleconsultation; Proficiency testing; Biomarker quantitation
AB The rapidly evolving field of digital microscopy supports the efficient exploitation of inherent information from stained glass slides to offer widespread utilization in breast histopathology. Digital image signals can be accurately measured, integrated into databases and shared through computer networks. Therefore, digital microscopy can boost telepathology-consultation, gradual- and postgradual teaching, proficiency testing, intra- and interlaboratory validation of biomarker screening interpretation, and automated image analysis of biomarker expression for both diagnostics and research applications. This is a brief highlight of the potential of digital microscopy in breast pathology applications.
C1 [Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Zsakovics, Ivett] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Diczhazi, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Ficsor, Levente] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Varga, S V] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
RP Krenacs, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM krenacst@gmail.com
CR Anderson WF, Luo S, Chatterjee N, Rosenberg PS, Matsuno RK, Goodman MT, Hernandez BY, Reichman M, Dolled-Filhart MP, O’Regan RM, Garcia-Closas M, Perou CM, Jatoi I, Cartun RW, Sherman ME, 2008, Human epidermal growth factor receptor-2 and estrogen receptor expression, a demonstration project using the residual tissue repository of the Surveillance, Epidemiology, and End Results, SEER, program. Breast Cancer Res Treat, Feb 7., DOI 10.1007/s10549-008-9918-3
Bloom K, Harrington D, 2004, Enhanced Accuracy of HER-2/neu immunohistochemical scoring using digital microscopy. Am J Clin Pathol 121:619–630
Borgen E, Naume B, Nesland JM, Nowels KW, Pavlak N, Ravkin I, Goldbard S, 2001, Use of automated microscopy for the detection of disseminated tumor cells in bone marrow samples. Cytometry 46:215–221
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Krenacs T, Ficsor L, Varga VS, Angeli V, Molnar B, 2008, Digital microscopy for boosting database integration and analysis in TMA studies. In: Simon R, ed, Methods in molecular biology. Humana, Totowa, NJ, in press)
Kumar RK, Velan GM, Korell SO, Kandara M, Dee FR, Wakefield D, 2004, Virtual microscopy for learning and assessment in pathology. J Pathol 204:613–618
Lundin M, Lundin J, Helin H, Isola J, 2004, A digital atlas of breast histopathology: an application of web based virtual microscopy. J Clin Pathol 57:1288–1291
Schrader T, Hufnagl P, Schlake W, Dietel M, 2005, Study of efficiency of teleconsultation: the Telepathology Consultation Service of the Professional Assoziation of German Pathologists for the screening program of breast carcinoma, in German). Verh Dtsch Ges Pathol 89:211–218
Skaland I, Ovestad I, Janssen EA, Klos J, Kjellevold KH, Helliesen T, Baak JP, 2008, Digital image analysis improves the quality of subjective HER-2 expression scoring in breast cancer. Appl Immunohistochem Mol Morphol 16(2):185–190
Teodorovic I, Isabelle M, Carbone A, Passioukov A, Lejeune S, Jamine D, Therasse P, Gloghini A, Dinjens WN, Lam KH, Oomen MH, Spatz A, Ratcliffe C, Knox K, Mager R, Kerr D, Pezzella F, van Damme B, van de Vijver M, van Boven H, Morente MM, Alonso S, Kerjaschki D, Pammer J, Lopez-Guerrero JA, Llombart Bosch A, van Veen EB, Oosterhuis JW, Riegman PH, 2006, TuBaFrost 6: virtual microscopy in virtual tumour banking. Eur J Cancer. 42:3110–3116
Witzig TE, Bossy B, Kimlinger T, Roche PC, Ingle JN, Grant C, Donohue J, Suman VJ, Harrington D, Torre-Bueno J, Bauer KD, 2002, Detection of circulating cytokeratin-positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy. Clin Cancer Res 8:1085– 1091
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 55
EP 58
DI 10.1007/s12253-008-9087-z
PG 4
ER
PT J
AU Kulka, J
Szasz, MA
Nemeth, Zs
Madaras, L
Schaff, Zs
Molnar, AI
Tokes, AM
AF Kulka, Janina
Szasz, Marcell Attila
Nemeth, Zsuzsanna
Madaras, Lilla
Schaff, Zsuzsa
Molnar, Arthur Istvan
Tokes, Anna-Maria
TI Expression of Tight Junction Protein Claudin-4 in Basal-Like Breast Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; Basal-like; Tissue microarray; Immunohistochemistry; Claudin-4
ID Breast carcinoma; Basal-like; Tissue microarray; Immunohistochemistry; Claudin-4
AB Claudins (CLDN) are tight junction proteins which contribute to the paracellular transport and ionic permeability of various epithelia. In recent years they came into focus for their suggested role in carcinogenesis and possible role in cancer therapy. According to our previous studies, in breast tissue CLDN4 is also related to the level of cellular differentiation. Thirty-eight estrogen (ER) and progesterone receptor (PgR) negative, HER2/neu negative, but cytokeratin 5/6 positive basal-like—mainly grade 3—breast carcinomas were compared with twenty-one grade 1, twenty-five grade 2 and twenty grade 3 non-basal-like invasive breast carcinomas, in respect to their CLDN4 expression. The immunohistochemical reactions were evaluated both semiquantitatively and by morphometrical analysis. Statistically significant difference (p=0.001) was observable regarding CLDN4 expression in the basal-like group as compared to grade 1 and 2 cancers. Further, CLDN4 expression was significantly higher (p=0.017) in the basal-like compared with the non-basal-like grade 3 carcinomas. Our results suggest that basal-like carcinomas are a subset of breast cancer with high level of CLDN4 protein expression. The finding is in accordance with our former observation that CLDN4 is indeed related to cellular differentiation. This observation may be seen as a further proof that basal-like carcinomas represent a separable group amongst grade 3 breast carcinomas.
C1 [Kulka, Janina] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Nemeth, Zsuzsanna] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Madaras, Lilla] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Molnar, Arthur Istvan] Semmelweis University, 1st Department of Surgery, 78 Ulloi ut, 1082 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
RP Kulka, J (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM kj@korb2.sote.hu
CR Perou CM, Sorlie T, Eisen MB et al, 2000, Molecular portraits of human breast tumours. Nature 406:747–752
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Livasy CA, Karaca G, Nanda R et al, 2006, Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Path 19:264–271
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 59
EP 64
DI 10.1007/s12253-008-9089-x
PG 6
ER
PT J
AU Josselin, N
Libouban, H
Dib, M
Ifrah, N
Legrand, E
Basle, FM
Audran, M
Chappard, D
AF Josselin, Nicolas
Libouban, Helene
Dib, Mamoun
Ifrah, Norbert
Legrand, Erick
Basle, Felix Michel
Audran, Maurice
Chappard, Daniel
TI Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B-cell lymphoma; Bone histomorphometry; Bone resorption; Dendritic cells; Monoclonal gammopathy; Myeloma; Osteoclast
ID B-cell lymphoma; Bone histomorphometry; Bone resorption; Dendritic cells; Monoclonal gammopathy; Myeloma; Osteoclast
AB The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments.
C1 [Josselin, Nicolas] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
[Libouban, Helene] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
[Dib, Mamoun] CHU d’Angers, Service d’hematologie and UPRES EA 3863, 49933 Angers, France.
[Ifrah, Norbert] CHU d’Angers, Service d’hematologie and UPRES EA 3863, 49933 Angers, France.
[Legrand, Erick] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
[Basle, Felix Michel] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
[Audran, Maurice] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
[Chappard, Daniel] U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
RP Chappard, D (reprint author), U922-LHEA, INSERM, Faculte de Medecine, 49045 Angers, France.
EM daniel.chappard@univ-angers.fr
CR Kyle RA, Therneau TM, Rajkumar SV et al, 2004, Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later. Mayo Clin Proc 79:859–866
Blouin S, Basle MF, Chappard D, 2008, Interactions between microenvironment and cancer cells in two animal models of bone metastasis. Br J Cancer 98:809–815
Bataille R, Chappard D, Basle M, 1995, Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo. Br J Haematol 90:721–724
Colla S, Zhan F, Xiong W et al, 2007, The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood 109:4470–4477
Tian E, Zhan F, Walker R et al, 2003, The role of the Wntsignaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494
Aubin JE, Bonnelye E, 2000, Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–913
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 65
EP 72
DI 10.1007/s12253-008-9092-2
PG 8
ER
PT J
AU Hussein, RAM
Abdel-Magid, MW
Saleh, R
Nada, E
AF Hussein, Rezk A Mahmoud
Abdel-Magid, M Wafaa
Saleh, Ramadan
Nada, Essam
TI Phenotypical Characteristics of the Immune Cells in Allergic Contact Dermatitis, Atopic Dermatitis and Pityriasis Rosea
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunity; Immune cells; Dermatitis
ID Immunity; Immune cells; Dermatitis
AB Allergic contact dermatitis (ACD) is a cellmediated, delayed type IV immunologic reaction. Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from a complex interaction between immunologic, genetic, and environmental factors. Pityriasis rosea (PR) is a self-limited eruption of unknown etiology. Immune cell infiltrate is a constant feature in the inflammatory skin diseases. Here, we performed phenotypical characterization of the immune cells in ACD, AD and PR (ten cases each). We performed immunohistochemical stains for B cells (CD20), T cells (CD3), histiocytes (CD68) and T cells with cytotoxic activity (granzyme-B). The data were compared with findings in 20 specimens of normal skin. The results were scored as mean values of positively stained immune cells. Immunohistochemistry showed significantly high counts of immune cells in lesional skin (ACD, AD and PR) compared to the normal one (p<0.05). In the lesional skin, the immune cells were composed predominantly of CD3+ T lymphocytes and CD68+ cells (histiocytes). Some of the CD3+ cells were granzyme B+. The counts of some immune cells (CD3+ and CD68+) were high in ACD compared to AD and PR. The counts of CD20+ and granzyme B+ cells were high in PR compared to ACD and AD. However, these differences did not reach the level of statistical significance. The present data describe the profile of the immune cell infiltrate in AD, ACD and PR. The cellmediated immunity seems to have critical role in the development of these lesions.
C1 [Hussein, Rezk A Mahmoud] Assuit University, Assuit University Hospitals, Department of PathologyAssuit, Egypt.
[Abdel-Magid, M Wafaa] Sohag University, Sohag University Hospitals, Department of DermatologySohag, Egypt.
[Saleh, Ramadan] Sohag University, Sohag University Hospitals, Department of DermatologySohag, Egypt.
[Nada, Essam] Sohag University, Sohag University Hospitals, Department of DermatologySohag, Egypt.
RP Hussein, RAM (reprint author), Assuit University, Assuit University Hospitals, Department of Pathology, Assuit, Egypt.
EM mrcpath17@gmail.com
CR McCleskey PE, Swerlick RA, 2001, Clinical review: thioureas and allergic contact dermatitis. Cutis 68:387–396
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Yawalkar N, Schmid S, Braathen LR, Pichler WJ, 2001, Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis. Br J Dermatol 144:1133–1139
Deguchi M, Aiba S, Ohtani H, Nagura H, Tagami H, 2002, Comparison of the distribution and numbers of antigen-presenting cells among T-lymphocyte-mediated dermatoses: CD1a+, factor XIIIa+, and CD68+ cells in eczematous dermatitis, psoriasis, lichen planus and graft-versus-host disease. Arch Dermatol Res 294:297–302
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Lugovic L, Lipozenocic J, Jakic-Razumovic J, 2001, Atopic dermatitis: immunophenotyping of inflammatory cells in skin lesions. Int J Dermatol 40:489–494
Nordlind K, Liden S, 1995, Gamma/delta T cells and human skin reactivity to heavy metals. Arch Dermatol Res 287:137–141
Kiekens RC, Thepen T, Oosting AJ, Bihari IC, Van De Winkel JG, Bruijnzeel-Koomen CA, Knol EF, 2001, Heterogeneity within tissue-specific macrophage and dendritic cell populations during cutaneous inflammation in atopic dermatitis. Br J Dermatol 145:957–965
Cantani A, 2001, Pathogenesis of atopic dermatitis, AD, and the role of allergic factors. Eur Rev Med Pharmacol Sci 5:95–117
Bjerke JR, 2002, The skin as an immunological organ. Tidsskr Nor Laegeforen 122:793–796
Yawalkar N, Hunger RE, Buri C, Schmid S, Egli F, Brand CU, Mueller C, Pichler WJ, Braathen LR, 2001, A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B. Am J Pathol 158:803–808
Caproni M, Torchia D, Antiga E, Terranova M, Volpi W, Del Bianco E, D’Agata A, Fabbri P, 2007, The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study. Br J Dermatol 156:312–319
Hussein MR, 2005, Tumour-infiltrating lymphocytes and melanoma tumorigenesis: an insight. Br J Dermatol 153:18–21
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 73
EP 79
DI 10.1007/s12253-008-9103-3
PG 7
ER
PT J
AU Bedaiwy, AM
Hussein, RAEM
Biscotti, Ch
Falcone, T
AF Bedaiwy, Ali Mohamed
Hussein, Rezk Abd-Elwahed Mahmoud
Biscotti, Charles
Falcone, Tommaso
TI Pelvic Endometriosis is Rarely Associated with Ovarian Borderline Tumours, Cytologic and Architectural Atypia: A Clinicopathologic Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometriosis; Cytologic atypia; Pattern atypia
ID Endometriosis; Cytologic atypia; Pattern atypia
AB Endometriotic foci, especially ovarian ones, with epithelial cytologic atypia may be precursors of cancer. This study presents an overview of the atypical cytological and histopathological findings associated with endometriosis. Six cases of endometriosis, with atypical histological and cytological changes, were obtained from the archives of the Department of Pathology at Cleveland Clinic Foundation between year 2000 and 2003. The size of the base from which these cases were drawn was 2000 cases of endometriosis. The age range of the patients was from 29 to 52 years. The clinical presentations included infertility (three cases), pelvic pain (three cases), adenexal and pelvic masses (four cases). Stage IV endometriosis with extensive pelvic involvement was found in two patients. Intraoperatively, the endometriotic lesions involved the ovaries (all cases); Cul de sac (four cases); urinary bladder (two cases); sigmoid colon, hemidiaphragms, and uterine vessels (one case each). The endometriotic lesions were associated with uterine leiomyomas (two patients) and adenocarcinoma of the vagina (one patient). Histologically, in addition to endometrial type glands and stroma, usually found in endometriosis, we observed both cytologic and pattern atypism involving the epithelium in all cases. The features of cytologic atypia included nuclear stratification, hyperchromatism, and pleomorphism. The features of pattern atypia were complex glandular pattern, papillary formations and psammoma bodies. In two cases, these features were sufficient for diagnosis of borderline Mullerian seromucinous tumours. One patient had recurred with metastatic adenocarcinoma of the vault. She died later from disseminated metastatic disease. There is a rare association between pelvic endometriosis and borderline ovarian tumours (three cases), cytologic and pattern atypia (two cases); mesothelial hyperplasia, endosalpingiosis (two cases), and metastasis (one case). Cytologic and pattern atypia can develop in the endometriotic foci and therefore, these lesions should be thoroughly scrutinized for presence of these changes. Our findings recommend surgical excision of these foci rather than their simple cauterization.
C1 [Bedaiwy, Ali Mohamed] The Assuit University Hospitals and The Cleveland Clinic Foundation, Department of Obstetrics and GynaecologyCleveland, OH, USA.
[Hussein, Rezk Abd-Elwahed Mahmoud] King Khalid University, Assir Central Hospital, Department of PathologyAbha, Saudi Arabia.
[Biscotti, Charles] The Cleveland Clinic Foundation, Department of PathologyCleveland, OH, USA.
[Falcone, Tommaso] The Cleveland Clinic Foundation, Department of Obstetrics and GynaecologyCleveland, OH, USA.
RP Hussein, RAEM (reprint author), King Khalid University, Assir Central Hospital, Department of Pathology, Abha, Saudi Arabia.
EM mrcpath17@gmail.com
CR Akahane T, Sekizawa A, Purwosunu Y et al, 2007, The role of p53 mutation in the carcinomas arising from endometriosis. Int J Gynecol Pathol 26:345–351
Ali-Fehmi R, Khalifeh I, Bandyopadhyay S et al, 2006, Patterns of loss of heterozygosity at 10q23.3 and microsatellite instability in endometriosis, atypical endometriosis, and ovarian carcinoma arising in association with endometriosis. Int J Gynecol Pathol 25:223–229
Bese T, Simsek Y, Bese N et al, 2003, Extensive pelvic endometriosis with malignant change in tamoxifen-treated postmenopausal women. Int J Gynecol Cancer 13:376–380
Clement PB, 2007, The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol 14:241–260
Edghill EL, Bingham C, Ellard S et al, 2006, Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84–90
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Groisman GM, Meir A, 2003, CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis. Arch Pathol Lab Med 127:1003–1006
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Kato N, Sasou S, Motoyama T, 2006, Expression of hepatocyte nuclear factor-1beta, HNF-1beta, in clear cell tumors and endometriosis of the ovary. Mod Pathol 19:83–89
Korner M, Burckhardt E, Mazzucchelli L, 2006, Higher frequency of chromosomal aberrations in ovarian endometriosis compared to extragonadal endometriosis: A possible link to endometrioid adenocarcinoma. Mod Pathol 19:1615–1623
Lee KR, Nucci MR, 2003, Ovarian mucinous and mixed epithelial carcinomas of Mullerian, endocervical-like, type: a clinicopathologic analysis of four cases of an uncommon variant associated with endometriosis. Int J Gynecol Pathol 22:42–51
Leiserowitz GS, Gumbs JL, Oi R et al, 2003, Endometriosisrelated malignancies. Int J Gynecol Cancer 13:466–471
Leng JH, Lang JH, Zhao XY et al, 2006, Visual and histologic analysis of laparoscopic diagnosis of endometriosis. Zhonghua Fu Chan Ke Za Zhi 41:111–113
Madej P, Plewka A, Madej JA et al, 2006, Nucleolar organizer regions, NORs, in adenomyosis. Pathol Res Pract 202:433–437
Marchino GL, Gennarelli G, Enria R et al, 2005, Diagnosis of pelvic endometriosis with use of macroscopic versus histologic findings. Fertil Steril 84:12–15
McCluggage WG, Bryson C, Lamki H et al, 2000, Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy. Int J Gynecol Pathol 19:276–279
Mhawech P, Kinkel K, Vlastos G et al, 2002, Ovarian carcinomas in endometriosis: an immunohistochemical and comparative genomic hybridization study. Int J Gynecol Pathol 21:401–406
Minkowitz G, 1996, Psammoma bodies in endometriosis: clinical, cytological, and physiopathological implications. Diagn Cytopathol 14:331–333
Mok SC, Kwong J, Welch WR et al, 2007, Etiology and pathogenesis of epithelial ovarian cancer. Dis Markers 23:367– 376
Obata K, Hoshiai H, 2000, Common genetic changes between endometriosis and ovarian cancer. Gynecol Obstet Invest 50, Suppl 1):39–43
Oral E, Ilvan S, Tustas E et al, 2003, Prevalence of endometriosis in malignant epithelial ovary tumours. Eur J Obstet Gynecol Reprod Biol 109:97–101
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Gruppo Italiano per lo Studio dell’Endometriosi, 2001, Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain. Hum Reprod 16:2668–2671
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Selvaggi SM, 2002, Pelvic endometriosis diagnosed on touch imprint cytology. Diagn Cytopathol 27:379–381
Spaczynski M, Kedzia W, 2001, Ovarian cancer and endometriosis. Ginekol Pol 72:268–272
Staats PN, Clement PB, Young RH, 2007, Primary endometrioid adenocarcinoma of the vagina: a clinicopathologic study of 18 cases. Am J Surg Pathol 31:1490–1501
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Thomas EJ, Campbell IG, 2000, Evidence that endometriosis behaves in a malignant manner. Gynecol Obstet Invest 50(Suppl 1): 2–10
Thomas EJ, Campbell IG, 2000, Molecular genetic defects in endometriosis. Gynecol Obstet Invest 50(Suppl 1):44–50
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 81
EP 88
DI 10.1007/s12253-008-9072-6
PG 8
ER
PT J
AU Eric, A
Juranic, Z
Milovanovic, Z
Markovic, I
Inic, M
Stanojevic-Bakic, N
Vojinovic-Golubovic, V
AF Eric, Aleksandra
Juranic, Zorica
Milovanovic, Zorka
Markovic, Ivan
Inic, Momcilo
Stanojevic-Bakic, Nevenka
Vojinovic-Golubovic, Vesna
TI Effects of Humoral Immunity and Calreticulin Overexpression on Postoperative Course in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Calreticulin; Humoral immunity; Surgery
ID Breast cancer; Calreticulin; Humoral immunity; Surgery
AB The aim was to investigate whether the humoral immunity and overexpression of calreticulin in tumor tissue determined before surgery, correlate with incidence of metastases in breast cancer patients within two years after operation. Before operation, their humoral immunity and overexpression of caleticulin and Her-2/neu in tumor tissue were analyzed by immunohystochemistry. In 23 patients with metastases in regionally lymph nodes, seven had Her-2/neu overexpression. Among those seven patients, three developed distant metastasis (two women one year and in one woman two years after surgery) and all of them showed the presence of stromal IgG immunoreactivity and overexpression of calreticulin in their tumors tissue. Preliminary data showed that serum IgG immunoreactivity to tumor stroma in combination with overexpression of calreticulin in tumor cells correlate with postoperative appearance of metastases, particularly in the group of patients with Her-2/neu overexpressed tumors and metastases in axillary lymph nodes.
C1 [Eric, Aleksandra] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Juranic, Zorica] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Milovanovic, Zorka] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Markovic, Ivan] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Inic, Momcilo] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Stanojevic-Bakic, Nevenka] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Vojinovic-Golubovic, Vesna] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
RP Eric, A (reprint author), Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, Serbia.
EM eric.aleksandra@ncrc.ac.yu
CR Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO 2001 Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Cancer Immun 1:4
Hayashi E, Kuramitsu Y, Okada F, Fujimoto M, Zhang X, Kobayashi M, Iizuka N, Ueyama Y, Nakamura K 2005 Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines. Proteomics 5(4):1024–1032
Dissemond J, Busch M, Kothen T, Mors J, Weimann TK, Lindeke A, Goos M, Wagner SN 2004 Differential downregulation of endoplasmic reticulum-residing chaperones calnexin and calreticulin in human metastatic melanoma. Cancer Lett 203(2):225–231
Sipione S, Ewen C, Shostak I, Michalak M, Bleackley RC 2005 Impaired cytolytic activity in calreticulin-deficient CTLs. J Immunol 174(6):3212–3219
Fraser SA, Karimi R, Michalak M, Hudig D 2000 Perforin lytic activity is controlled by calreticulin. J Immunol 164(8):4150–4155
Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G 2005 Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement. J Clin Oncol 23(7):1379–1389
Ross JS, Fletcher JA 1998 The HER-2/neu Oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. Oncologist 3(4):237–252
Barbera-Guillem E, Nyhus JK, Wolford CC, Friece CR, Sampsel JW 2002 Vascular endothelial growth factor secretion by tumorinfiltrating macrophages essentially supports tumor angiogenesis and IgG immune complexes potentate the process. Cancer Res 62:7042–7049
Shushakova N, Eden G, Dangers M, Zwirner J, Menne J, Gueler F, Luft FC, Haller H, Dumler I 2005 The urokinase/urokinase receptor system mediates the IgG immune complex-induced inflammation in lung. J Immunol 175(6):4060–4068
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 89
EP 90
DI 10.1007/s12253-008-9112-2
PG 2
ER
PT J
AU Yu, X
Xu, X
Han, B
Zhou, R
AF Yu, Xiaoling
Xu, Xiaohui
Han, Baojian
Zhou, Rongxiang
TI Inhibitor of DNA Binding-1 Overexpression in Prostate Cancer: Relevance to Tumor Differentiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Id1; Protein expression; mRNA quantitation; Differentiation
ID Prostate cancer; Id1; Protein expression; mRNA quantitation; Differentiation
AB Inhibitor of DNA binding-1 (Id1) is a dominantnegative regulator of basic helix–loop–helix transcription factor, which control malignant cell behaviors in several types of carcinomas. This study aimed to find the relationship between Id1 expression and some clinical parameters. Paraffin-embedded tissue specimens from two normal human prostates, 12 benign prostatic hyperplasia (BPH), 43 prostate cancers(PCa) were detected by immunofluorescence assay. Prostatectomy samples from 11 BPH and 28 PCa were used for real time RT-PCR. The relationship between Id1 staining and several patient’s clinical parameters, including Gleason grade, PSA, clinical stage, and size of tumor, was further analyzed. Significant up-regulated Id1 protein was shown in prostate cancer specimens, while only weak expression in some BPH samples (5/12). Analyzed by image software, the mean proportion of Id1 positive staining remarkably increased with the increasing of Gleason grade in prostate cancer specimens (r=0.9967, P<0.01). Id1 expression was not significantly associated with PSA, TNM stage or tumor size. Furthermore, the average mRNA of prostate cancer was 3.09 times of BPH. This study confirms that Id1 protein and mRNA are over expressed in prostate cancer tissues. Overexpression of Id1 protein correlates with tumor tissue differentiation. We propose that Id1 over expression can be used in the analysis of the progression of prostate cancer.
C1 [Yu, Xiaoling] Medical College of Qingdao University, Department of PathophysiologyQingdao, China.
[Xu, Xiaohui] Medical College of Qingdao University, Department of PathophysiologyQingdao, China.
[Han, Baojian] Medical College of Qingdao University, Department of Urinary SurgeryQingdao, China.
[Zhou, Rongxiang] Medical College of Qingdao University, Department of Urinary SurgeryQingdao, China.
RP Yu, X (reprint author), Medical College of Qingdao University, Department of Pathophysiology, Qingdao, China.
EM xiaoling_yu2004@163.com
CR Jemal A, Siegel R, Ward E et al, 2007, Cancer statistics, 2007. CA Cancer J Clin 57:43–66
Hsing AW, Tsao L, Devesa SS, 2000, International trends and patterns of prostate cancer incidence and mortality. Int Cancer 85:60–67,, review)
Sim HG, Cheng CW, 2005, Changing demography of prostate cancer in Asia. Eur J Cancer 41:834–845
Gu F, 2000, Epidemiological survey of benign prostatic hyperplasia and prostate cancer in China. Chin Med J, Engl, 113:299–302
Hsing AW, Devesa SS, Jin F et al, 1998, Rising incidence of prostate cancer in Shanghai. Cancer Epidemiol Biomarkers Prev 7:83–84, letter)
Hasskarl J, Munger K, 2002, Id proteins—tumor marker or oncogenes? Cancer Biology and Therapy 1:91–96, review)
Perk J, Iavarone A, Benezra R, 2005, Id family of helix–loop– helix proteins in cancer. Nat Rev Cancer 5:603–604
Han S, Guo C, Hong L et al, 2004, Expression and significance of Id1 helix–loop–helix protein overexpression in gastric cancer. Cancer Lett 216:63–71
Matsuda Y, Yamagiwa S, Takamura M et al, 2005, Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16. Cancer 104:1037–1044
Straume O, Akslen LA, 2005, Strong expression of ID1 protein is associated with decreased survival, increased expression of ephrin-A1/EPHA2, and reduced thrombospondin-1 in malignant melanoma. Br J Cancer 93:933–938
Benezra R, Davis RL, Lockshon D et al, 1990, The protein Id: a negative regulator of helix–loop–helix DNA binding proteins. Cell 61:49–59
Alani RM, Hasskarl J, Grace M et al, 1999, Immortalization of primary human keratinocytes by the helix–loop–helix protein,Id- 1. Proc Natl Acad Sci USA 96:9637–9641
Lyden D, Young AZ, Zagzag D et al, 1999, Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401:670–677
Ruzinova MB, Benezra R, 2003, Id proteins in development, cell cycle and cancer. Trends Cell Biol 13:410–418
Wong YC, Wang X, Ling MT, 2004, Id-1 expression and cell survival. Apoptosis 9:279–289,, review)
Jang KS, Han HX, Paik SS et al, 2006, Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intratumoral microvessel density in ER-negative/node-positive breast cancer. Cancer Lett 244:203–210
Chetcuti A, Marqan S, Mann S et al, 2001, Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array. Prostate 47:132–140
Ouyang XS, Wang X, Lee DT et al, 2002, Overexpression of ID-1 in prostate cancer. J Urol 167:2598–2602
Coppe JP, Itahana Y, Moore DH et al, 2004, Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression. Clin Cancer Res 10:2044–2051
Yu DS, Hsieh DS, Chang SY, 2006, Increasing expression of GST-pi MIF, and ID1 genes in chemoresistant prostate cancer cells. Arch Androl 52:275–281
Lin JC, Chang SY, Hsieh DS et al, 2005, Modulation of mitogenactivated protein kinase cascades by differentiation-1 protein: acquired drug resistance of hormone independent prostate cancer cells. J Urol 174:2022–2026
Ouyang XS, Wang X, Ling MT et al, 2002, Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway. Carcinogenesis 23: 721–725
Asirvatham AJ, Schmidt MA, Chaudhary J, 2006, Non-redundant inhibitor of differentiation, Id, gene expression and function in human prostate epithelial cells. Prostate 66:921–935
Perk J, Gil-Bazo I, Chin Y et al, 2006, Reassessment of id1 protein expression in human mammary, prostate, and bladder cancers using a monospecific rabbit monoclonal anti-id1 antibody. Cancer Res 66:10870–10877
Schindl M, Schoppmann SF, Strobel T et al, 2003, Level of Id-1 protein expression correlates with poor differentiation, enhanced malignant potential and more aggressive clinical behavior of epithelial ovarian tumors. Clin Cancer Res 9:779–785
Lin CQ, Singh J, Murata K et al, 2000, A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. Cancer Res 60:1332–1340
Ling MT, Wang X, Lee DT et al, 2004, Id1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor, EGF-R). Carcinogenesis 25:517–525
Ling MT, Wanq X, Ouyanq XS et al, 2002, Activation of MAPK signaling pathway is essential for Id1 induced serum independent prostate cancer cell growth. Oncogene 21:8498–8505
Ling MT, Wang X, Ouyang XS et al, 2003, Id1 expression promotes cell survival through activation of NF-kB signaling pathway in prostate cancer cells. Oncogene 22:4498–4508
Fong S, Itahana Y, Sumida T et al, 2003, Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proc Natl Acad Sci USA 100:13543–13548
Fong S, Debs RJ, Desprez PY, 2004, Id genes and proteins as promising targets in cancer therapy. Trends Mol Med 10:387–392, review)
Tsuchiya T, Okaji Y, Tsuno NH et al, 2005, Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer. Cancer Sci 96:784–790
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 91
EP 96
DI 10.1007/s12253-008-9096-y
PG 6
ER
PT J
AU Mannweiler, S
Pummer, K
Auprich, M
Galle, G
Mehes, G
Ratschek, M
Tsybrovskyy, O
Moinfar, F
AF Mannweiler, Sebastian
Pummer, Karl
Auprich, Marco
Galle, Gunter
Mehes, Gabor
Ratschek, Manfred
Tsybrovskyy, Oleksiy
Moinfar, Farid
TI Diagnostic Yield of Touch Imprint Cytology of Prostate Core Needle Biopsies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biopsy; Diagnosis; Imprint cytology; Prostate; Cancer
ID Biopsy; Diagnosis; Imprint cytology; Prostate; Cancer
AB Touch imprint cytology may provide additional information to core needle biopsy interpretation according to previous reports. The aim of this study was to investigate the diagnostic yield of this method in the diagnosis of prostate carcinoma. For this purpose, 452 transrectal prostate needle biopsies were evaluated from 56 patients. All patients were clinically suspicious of having prostate carcinoma. Two touch imprints were prepared from each fresh biopsy cylinder. Results of the standard histology and of the touch imprint evaluation were compared. Histologically negative biopsy cylinders were further evaluated for prostate carcinoma by fine step serial sectioning. The standard histological examination showed adenocarcinoma in 27 patients. Touch imprint cytology revealed atypical cells suspicious of carcinoma in 38 patients. This group included all 27 patients with positive standard histology and further 11 patients with initially negative core biopsy. Following serial sectioning, in three out of these 11 samples, histological evidence of a carcinoma could be proven. Fine step serial sectioning of all 29 core biopsies negative for carcinoma by standard histological examination, 26 patients remained negative. All three core biopsies initially negative by standard histology but positive after serial sectioning had cytology findings suspicious of carcinoma. We conclude, that in problematic cases the additional use of touch imprint cytology and serial sectioning of prostate core needle biopsies significantly improve the diagnostic accuracy.
C1 [Mannweiler, Sebastian] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Pummer, Karl] Medical University of Graz, Department of UrologyGraz, Austria.
[Auprich, Marco] Medical University of Graz, Department of UrologyGraz, Austria.
[Galle, Gunter] Medical University of Graz, Department of UrologyGraz, Austria.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Ratschek, Manfred] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Tsybrovskyy, Oleksiy] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Moinfar, Farid] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
RP Mannweiler, S (reprint author), Medical University of Graz, Department of Pathology, A-8036 Graz, Austria.
EM Sebastian.Mannweiler@meduni-graz.at
CR Hodge KK, McNeal JE, Terris MK et al, 1989, Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 142:71–74
Fleshner NE, O, Sullivan M, Fair WR, 1997, Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate. J Urol 158:505–508
Jacobs TW, Silverman JF, Schroeder B, Raza S, Baum JK, Schnitt SJ, 1999, Accuracy of touch imprint cytology of image-directed breast core needle biopsies. Acta Cytol 43:169–174
Gentry JF, 1986, Pelvic lymph node metastases in prostatic carcinoma. The value of touch imprint cytology. Am J Surg Pathol 10:718–727
Chieco P, Bertaccini A, Giovannini C, Stecca BA, Martorana G, 2001, Telomerase activity in touch-imprint cell preparation from fresh prostate needle biopsy specimens. Eur Urol 40:666–672
Lo J, Billie-Jo K, Amling CHL, Robertson CN, Layfield LJ, 1996, Correlation of DNA ploidy and histologic diagnosis from prostate core-needle biopsies: is DNA ploidy more sensitive than histology for the diagnosis of carcinoma in small specimens? J Surg Oncol 63:41–45
Eble JN, Sauter G, Epstein JI, Sesterhenn IA, 2004, Tumours of the urinary system and male genital organs. World Health Organization classification of tumours. IARC, Lyon
Willems JS, Lowhagen T, 1981, Transrectal fine-needle aspiration biopsy for cytologic diagnosis and grading of prostatic carcinoma. Prostate 2:381–395
Epstein NA, 1976, Prostatic biopsy. A morphologic correlation of aspiration cytology with needle biopsy histology. Cancer 38:2078–2087
Leistenschneider W, Nagel R, 1984, Atlas of Prostatic Cytology. Springer-Verlag, Berlin Heidelberg, New York, Tokyo
Zincke H, Campbell JT, Utz DC, Farrow GM, Anderson MJ Jr., 1973, Confidence in the negative transrectal needle biopsy. Surg Gynecol Obstet 136:78–80
Rabbani F, Stroumbakis N, Kava BR, Cookson MS, Fair WR, 1998, Incidence and clinical significance of false-negative sextant prostate biopsies. J Urol 159:1247–1250
Eskew LA, Bare RL, McCullough DL, 1997, Systematic 5 region biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 157:199–202
Durkan GC, Greene DR, 2000, Diagnostic dilemmas in detection of prostate cancer in patients undergoing transrectal ultrasoundguided needle biopsy of the prostate. Pros Canc Pros Dis 3:13–20
Kao J, Upton M, Zhang P, Rosen S, 2002, Individual prostate biopsy core embedding facilitates maximal representation. J Urol 168:496–499
Cserni G, 2004, A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol 57:467–471
Cserni G, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Bussolati G et al, 2003, Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. Eur J Cancer 39:1654–1667
Lane RB, Lane CG, Mangold KA, Johnson MH, Allsbrook WC, 1998, Needle biopsies of the prostate. What constitutes adequate histologic sampling? Arch Pathol Lab Med 122:833–835
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 97
EP 101
DI 10.1007/s12253-008-9114-0
PG 5
ER
PT J
AU Cserni, T
O’ Donnel, A
Paran, S
Puri, P
AF Cserni, Tamas
O’ Donnel, Annemarie
Paran, Sri
Puri, Prem
TI Correlation of Enteric NADPH-d Positive Cell Counts with the Duration of Incubation Period in NADPH-d Histochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Positive cell counts; Incubation time; NADPH-d histochemistry
ID Positive cell counts; Incubation time; NADPH-d histochemistry
AB Nicotinamide adenine dinucleotide phosphatediaphorase (NADPH-d) staining can be used in the enteric nervous system to determine nitrergic neuronal counts, critical in motility disorders such as intestinal neuronal dysplasia and hypoganglionosis. The reported incubation periods of specimens with NADPH-d staining solution has varied from 2 to 24 h. The aim of this study is to investigate the impact of the incubation period on the overall NADPHd positive cell counts in porcine rectal submucosal plexus. The submucosal plexus of rectal specimens from 12-weekold pigs (n=5) were studied. Conventional frozen sections were used to identify nitrergic neurons while whole-mount preparations were used to quantify the effect of prolonged duration of incubation on positively identified ganglion cells with NADPH-d histochemistry. The same submucosal ganglia on the conventional sections, and a minimum of 12 ganglia per whole-mount preparation specimen were photographed sequentially at 2, 6, and 24 h and used to count the number of nitrergic cells per ganglion. The same staining solution was used throughout the experiment. Results were analysed using a one-way ANOVA test. Prolonged incubation with the staining solution revealed new NADPH-d positive cells in the ganglia on the conventional sections. The total number of neurons counted in the 12 adjacent ganglia in the whole-mount specimens was 180±55, the mean neuronal cell per ganglion was 15±8 after 2 h of incubation. This increased to 357±17, and to 29±12 after 6 h (p<0.05). A further increase was observed of 515±19 and 43±17 after 24 h (p<0.05). When the photomicrographs were retrospectively analysed, not even the outline of the neuronal cells that stained with prolonged incubation was evident at the earlier time points. NADPH-d positive cell counts increase in proportion to the duration of incubation in NADPH-d histochemistry. Comparative studies attempting to quantify nitrergic cell counts in dysmotility disorders must take into account the variability in NADPH-d positive cell count associated with prolonged incubation in NADPH-d histochemistry.
C1 [Cserni, Tamas] University College Dublin, Our Lady’s Children’s Hospital, Children’s Research CentreDublin, Ireland.
[O’ Donnel, Annemarie] University College Dublin, Our Lady’s Children’s Hospital, Children’s Research CentreDublin, Ireland.
[Paran, Sri] University College Dublin, Our Lady’s Children’s Hospital, Children’s Research CentreDublin, Ireland.
[Puri, Prem] University College Dublin, Our Lady’s Children’s Hospital, Children’s Research CentreDublin, Ireland.
RP Cserni, T (reprint author), University College Dublin, Our Lady’s Children’s Hospital, Children’s Research Centre, Dublin, Ireland.
EM tcserni@yahoo.com
CR Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG, 1990, Nitric oxide as an inhibitory nonadrenergic non-cholinergic neurotransmitter. Nature 345:346–347
Boeckxstaens GE, Pelckmans PA, Bult H, De Man JG, Herman AG, Van Maercke YM, 1990, Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol 190:239–246
Stark ME, Bauer AJ, Sarr MG, Szurszewski JH, 1993, Nitric oxide mediates inhibitory nerve input in human and canine jejunum. Gastroenterology 104:398–409
Burleigh DE, 1992, Ng-nitro-L-arginine reduces nonadrenergic, noncholinergic relaxations of human gut. Gastroenterology 102:679–683
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 103
EP 107
DI 10.1007/s12253-008-9081-5
PG 5
ER
PT J
AU Chuangui, Ch
Sun, J
Liu, G
Chen, J
AF Chuangui, Chen
Sun, Jinjin
Liu, Geng
Chen, Jianqiu
TI Effect of Small Interference RNA Targeting HIF-1α Mediated by rAAV Combined L-Ascorbate on Pancreatic Tumors in Athymic Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Recombinant adeno-associated virus (rAAV); Hypoxia inducible factor (HIF); Small interference RNA (siRNA); L-Ascorbate
ID Recombinant adeno-associated virus (rAAV); Hypoxia inducible factor (HIF); Small interference RNA (siRNA); L-Ascorbate
AB To study the effect of recombinant adenoassociated virus (rAAV) vector bearing small inference RNA (siRNA) targeting hypoxia inducible factor 1α (HIF-1α) combined L-ascorbate on pancreatic tumors in athymic mice primarily. A cassette encoding siRNA targeting HIF-1α mediated by rAAV was constructed, giving rAAV-siHIF. In vitro, rAAV-hrGFP, rAAV-siHIF and L-ascorbate which were used alone or in combination were delivered to exponentially growing MiaPaCa2 cells. Then, we examined the expression of HIF-1α mRNA and protein, the secretion of VEGF in MiaPaCa2 cells under hypoxic condition with Real-time PCR, Western Blot, ELISA, respectively. In vivo, MiaPaCa2 cells were inoculated subcutaneously on the back of nude mice. Nude mice with xenograft tumor were randomly divided into equal groups and were injected with rAAV-hrGFP or rAAV-siHIF or were fed with L-ascorbate. Then, we measured the size of tumor every 3 days and drew a tumor growth curve. After 30 days, all mice were sacrificed and the tumors were dissected. At last, we examined the expression of HIF-1α, VEGF and CD34 by immunohistochemistry and counted micro-vessel density (MVD). In vitro, we found that rAAV-siHIF could inhibit the expression of HIF-1α mRNA and protein in MiaPaCa2 human pancreatic cancer cells but L-ascorbate could only restrain the expression of HIF-1α protein. Moreover, rAAVsiHIF and L-ascorbate could all inhibit the secretion of vascular VEGF. In vivo, we found that rAAV-siHIF could inhibit the growth of nude mice xenograft tumor and the expression of HIF-1α and VEGF and MVD while Lascorbate can only inhibit the growth of xenograft tumor in the early and middle stage. These results suggest that rAAVsiHIF and L-ascorbate can inhibit the growth of nude mice xenograft tumor and HIF-1α could be a target of pancreatic cancer genetic and pharmacological therapy.
C1 [Chuangui, Chen] The Second Hospital of TianJin Medical University, Department of Surgery, 300211 Tianjin, China.
[Sun, Jinjin] The Second Hospital of TianJin Medical University, Department of Surgery, 300211 Tianjin, China.
[Liu, Geng] The Second Hospital of TianJin Medical University, Department of Surgery, 300211 Tianjin, China.
[Chen, Jianqiu] The Second Hospital of TianJin Medical University, Department of Surgery, 300211 Tianjin, China.
RP Chen, J (reprint author), The Second Hospital of TianJin Medical University, Department of Surgery, 300211 Tianjin, China.
EM chenchen20071011@yahoo.com.cn
CR Yin T, Wang C, Liu T et al, 2007, Expression of snail in pancreatic cancer promotes metastasis and chemoresistance. J Surg Res 141:196–203
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Semenza GL, 2003, Targeting HIF-1 for cancer therapy. Nature Rev 3:721–732
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Lu H, Forbes RA, Verma A, 2002, Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Bio Chem 26:23111–23115
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Andre T, Chastre E, Kotelevets L et al, 1998, Tumoral angiogenesis: physiopathology, prognostic value and therapeutic perspectives. Rev Med Interne 19:904–913
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Yang ZF, Poon RT, To J et al, 2004, The potential role of hypoxia inducible factor 1 alpha in tumor progression after hypoxia and chemotherapy in hepatocellular carcinoma. Cancer Res 64:5496– 5503
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 109
EP 114
DI 10.1007/s12253-008-9063-7
PG 6
ER
PT J
AU Perse, M
Cerar, A
Injac, R
Strukelj, B
AF Perse, Martina
Cerar, Anton
Injac, Rade
Strukelj, Borut
TI N-methylnitrosourea Induced Breast Cancer in Rat, the Histopathology of the Resulting Tumours and its Drawbacks as a Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Animal model; Breast cancer; Histopathology; N-methylnitrosourea; Rats
ID Animal model; Breast cancer; Histopathology; N-methylnitrosourea; Rats
AB Several animal models of breast cancer have been developed to study various aspects of breast cancer biology. Substantial evidence suggests that the N-methylnitrosourea (MNU) animal model mimics human breast cancer in many respects. It has therefore been used extensively to evaluate preventive and therapeutic agents for human breast cancer. Chemically induced rodent models are also suitable for studying malignant progression. Recently, Liska et al. [7] established two protocols of MNU administration depending on the animal’s age and number of applications of carcinogen, with the aimof investigating the advanced stages of mammary gland tumours. We used the same protocol as Liska but have obtained substantially different results. These results are presented and discussed in the frame of suggested key drawbacks of the MNU induced breast cancer rat model, as a contribution to the debate about the suitability of that model for evaluating preventive and therapeutic agents.
C1 [Perse, Martina] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1105 Ljubljana, Slovenia.
[Cerar, Anton] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1105 Ljubljana, Slovenia.
[Injac, Rade] University of Ljubljana, Faculty of Pharmacy, Institute of Pharmaceutical Biology, Askerceva 7, 1000 Ljubljana, Slovenia.
[Strukelj, Borut] University of Ljubljana, Faculty of Pharmacy, Institute of Pharmaceutical Biology, Askerceva 7, 1000 Ljubljana, Slovenia.
RP Perse, M (reprint author), University of Ljubljana, Faculty of Medicine, Institute of Pathology, 1105 Ljubljana, Slovenia.
EM martina.perse@mf.uni-lj.si
CR Parkin DM, Bray F, Ferlay J et al, 2005, Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Clarke R, 1996, Animal models of breast cancer: their diversity and role in biomedical research. Breast Cancer Res Treat 39:1–6
Russo J, Russo IH, 1996, Experimentally induced mammary tumors in rats. Breast Cancer Res Treat 39:7–20
McCormick DL, Adamowski CB, Fiks A et al, 1981, Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. Cancer Res 41:1690–1694
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Thompson HJ, Adlakha H, 1991, Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1- methyl-1-nitrosourea. Cancer Res 51:3411–3415
Liska J, Galbavy S, Macejova D et al, 2000, Histopathology of mammary tumours in female rats treated with 1-methyl-1- nitrosourea. Endocr Regul 34:91–96
Thompson HJ, Adlakha H, Singh M, 1992, Effect of carcinogen dose and age at administration on induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. Carcinogenesis 13:1535–1539
Thompson HJ, McGinley JN, Rothhammer K et al, 1995, Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis 16:2407–2411
Russo J, Russo IH, 2000, Atlas and histologic classification of tumors of the rat mammary gland. Journal of Mammary Gland Biology and Neoplasia 5:187–200
Chan MM, Lu X, Merchant FM et al, 2005, Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer. Carcinogenesis 26:1343– 1353
Badawi AF, Eldeen MB, Liu Y et al, 2004, Inhibition of rat mammary gland carcinogenesis by simultaneous targeting of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma. Cancer Res 64:1181–1189
Kubatka P, Ahlers I, Ahlersova E et al, 2003, Chemoprevention of mammary carcinogenesis in female rats by rofecoxib. Cancer Lett 202:131–136
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Sumova A, Bendova Z, Sladek M et al, 2004, Seasonal molecular timekeeping within the rat circadian clock. Physiol Res 53 Suppl 1:S167–S176
De Jonage-Canonico MB, Lenoir V, Martin A et al, 2003, Long term inhibition by estradiol or progesterone of melatonin secretion after administration of a mammary carcinogen, the dimethyl benz, a)anthracene, in Sprague–Dawley female rat; inhibitory effect of Melatonin on mammary carcinogenesis. Breast Cancer Res Treat 79:365–377
Halberg F, 1964, Grundlagenforschung zur Atiologie des Karzinoms. Arztl Fortb 2:67–77
Kubatka P,Ahlersova E, Ahlers I et al, 2002)Variability of mammary carcinogenesis induction in female Sprague–Dawley andWistar:Han rats: the effect of season and age. Physiol Res 51:633–640
Lu J, Jiang C, Mitrenga T et al, 1998, Pathogenic characterization of 1-methyl-1-nitrosourea-induced mammary carcinomas in the rat. Carcinogenesis 19:223–227
Reznik G, Ward JM, 1981, Morphology of neoplastic lesions in the clitoral and prepucial gland of the F334 rat. J Cancer Res Clin Oncol 101:249–263
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Ito O, Okamoto T, Fujimoto N et al, 1994, Inhibition of mammary tumours by pretreatment with 17 beta-estradiol in F344 rats induced with N-methyl-N-nitrosourea. Jpn J Cancer Res 85:279–283
Workman P, Balmain A, Hickman JA et al, 1988, UKCCCR guidelines for the welfare of animals in experimental neoplasia. Lab Anim 22:195–201
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 115
EP 121
DI 10.1007/s12253-008-9117-x
PG 7
ER
PT J
AU Anagnostou, V
Tiniakos, D
Chorti, M
Kiagia, M
Tourkantonis, I
Alamara, Ch
Syrigos, NK
AF Anagnostou, K. Vasiliki
Tiniakos, G. Diana
Chorti, Maria
Kiagia, Maria
Tourkantonis, Ioannis
Alamara, Christina
Syrigos, Nik Konstantinos
TI Right Sited Renal Cell Carcinoma Metastasizing to the Contralateral Ovary: Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; Ovarian metastasis
ID Renal cell carcinoma; Ovarian metastasis
AB Ovarian metastases from renal cell carcinoma are rare, with only 22 cases reported in the literature. We report a case of a 45-year-old woman, who developed left ovarian and right adrenal metastases 3 months after diagnosis of clear cell renal cell carcinoma and review the literature. This is the fourth reported case of right renal cell carcinoma metastasizing to the left ovary. The patient is alive 4 years after resection of the ovarian tumor, treated with sunitinib. We conclude that, although rare, metastatic renal cell carcinoma should be included in the differential diagnosis of ovarian tumors with clear cell histology.
C1 [Anagnostou, K. Vasiliki] University of Athens, 3rd Department of Medicine, Oncology Unit, Building Z, Sotiria General Hospital, Mesogion 152, 115 27 Athens, Greece.
[Tiniakos, G. Diana] University of Athens, School of Medicine, Laboratory of Histology & EmbryologyAthens, Greece.
[Chorti, Maria] Sismanoglion Hospital, Department of PathologyAthens, Greece.
[Kiagia, Maria] University of Athens, 3rd Department of Medicine, Oncology Unit, Building Z, Sotiria General Hospital, Mesogion 152, 115 27 Athens, Greece.
[Tourkantonis, Ioannis] University of Athens, 3rd Department of Medicine, Oncology Unit, Building Z, Sotiria General Hospital, Mesogion 152, 115 27 Athens, Greece.
[Alamara, Christina] University of Athens, 3rd Department of Medicine, Oncology Unit, Building Z, Sotiria General Hospital, Mesogion 152, 115 27 Athens, Greece.
[Syrigos, Nik Konstantinos] University of Athens, 3rd Department of Medicine, Oncology Unit, Building Z, Sotiria General Hospital, Mesogion 152, 115 27 Athens, Greece.
RP Anagnostou, V (reprint author), University of Athens, 3rd Department of Medicine, Oncology Unit, 115 27 Athens, Greece.
EM valsamo.anangostou@yale.edu
CR Lineham M, Zbar B, Bates S et al, 2005, Cancer principals and practice of oncology: cancer of the kidney and ureter, 7th edn. Lippincott, New York, pp 1139–1151
Scully RE, Young RH, Clement PB, 1998, Atlas of tumor pathology: tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. Armed Forces Institute of Pathology, Washington, D.C., pp 141–151, 153, 160, 352, 353
Insabato L, De Rosa G, Franco R et al, 2003, Ovarian metastasis from renal cell carcinoma: a report of three cases. Int J Surg Pathol 11:309–312
Johansson H, 1960, Clinical aspects of metastatic ovarian cancer of extragenital origin. Acta Obstet Gynecol Scand 39:681–697
Kato Y, Numata A, Wada N et al, 2006, A case of metastatic renal cell carcinoma to the ovary. Hinyokika Kiyo 52:923–927
Liu FS, Ho ES,Lu F,Chang CY, 1992, Solitary metastasis of renal cell carcinoma to the ovaries: a case report. Zhonghua Yi Xue Za Zhi, Taipei, 50:165–168
Madersbacher S, Ponholzer A, Franz K et al, 2007, Synchronous bilateral renal cell cancer with a single ovarian metastasis and a fibromuscular dysplasia of the renal artery. Aktuelle Urol 38:52–54
Shinojima T, Nakajima Y, Kiguchi H, 2001, Renal cell carcinoma metastatic to the ovary: a case report. Nippon Hinyokika Gakkai Zasshi 92:694–697
Spencer JR, Eriksen B, Garnett JE, 1993, Metastatic renal tumor presenting as ovarian clear cell carcinoma. Urology 41:582–584
Stadiem ML, 1937, An ovarian hypernephroma. Am J Surg 37:312–318
Stefani P, Selli C, Nicita G et al, 1981, Angiographic aspects of renal cell carcinoma metastatic to the female genitalia. Cardiovasc Interv Radiol 4:183–186
Valappil SV, Toon PG, Anandaram PS, 2004, Ovarian metastasis from primary renal cell carcinoma: report of a case and review of literature. Gynecol Oncol 94:846–849
Young RH, Hart WR, 1992, Renal Cell Carcinoma metastatic to the ovary: a report of three cases emphasizing possible confusion with ovarian clear cell ademocarcinoma. Int J Gynec Pathol 11:96–104
Baker PM, Oliva E, 2004, Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: an update. Int J Gynecol Pathol 24:39–55
Nolan LP, Heatley MK, 2001, The value of immunohistochemistry in distinguishing between clear cell carcinoma of the kidney and the ovary. Int J Gynecol Pathol 20:155–159
Skinnider BF, Folpe AL, Hennigar RA, Lim SD et al, 2005, Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue. Potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol 29:747–754
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 123
EP 127
DI 10.1007/s12253-008-9039-7
PG 5
ER
PT J
AU Burkadze, G
Turashvili, G
AF Burkadze, George
Turashvili, Gulisa
TI A Case of Osteoclast-like Giant Cell Tumor of the Pancreas Associated with Borderline Mucinous Cystic Neoplasm
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteoclast-like giant cell tumor; Mucinous cystic neoplasm; Immunohistochemistry; Pancreas
ID Osteoclast-like giant cell tumor; Mucinous cystic neoplasm; Immunohistochemistry; Pancreas
AB A 34-year-old, previously healthy female presented with severe acute upper quadrant abdominal pain and an 11-cm cystic mass in the tail of the pancreas. The patient underwent distal pancreatectomy with total gross excision of the mass. Grossly, the mass consisted of a multiloculated cystic lesion measuring 11.7 cm in its greatest dimension. An irregular solid lobulation at the lateral aspect of the cyst was visible, measuring 3 cm in the largest dimension. Histologically, there were two distinct components: a mucinous, neoplastic epithelial cyst with few foci of moderate atypia, and nodular spindle cell areas containing multinucleated tumor giant cells. Immunohistochemically, the multinucleated giant cells were positive for vimentin, CD68 and CD45, and negative for cytokeratin and epithelial membrane antigen (EMA). The spindle cells of hypercellular stroma were stained for vimentin, but not for EMA or carcinoembryonic antigen (CEA). Neuronspecific enolase (NSE), S100 and Ki-67 showed no reactivity. The histological diagnosis "osteoclast-like giant cell tumor of the pancreas associated with borderline mucinous cystic neoplasm" was made. The patient recovered and is free of disease 4 years after the diagnosis.
C1 [Burkadze, George] N. Kipshidze Central University Clinic, Department of Pathology, Vazha-Pshavela Avenue, 0160 Tbilisi, Georgia.
[Turashvili, Gulisa] N. Kipshidze Central University Clinic, Department of Pathology, Vazha-Pshavela Avenue, 0160 Tbilisi, Georgia.
RP Burkadze, G (reprint author), N. Kipshidze Central University Clinic, Department of Pathology, 0160 Tbilisi, Georgia.
EM gburkadze@hotmail.com
CR Alguacil-Garcia A, Weiland L, 1977, The histologic spectrum, prognosis, and histogenesis of the sarcomatoid carcinoma of the pancreas. Cancer 39:1181–1189
Batsakis J, Ordonez N, Sevidal P, Baker JR, 1988, Osteoclasttype giant cell neoplasms of the parotid gland. J Laryngol Otol 102:901–904
Dizon M, Multhaulpt H, Paskin D, Warhol MJ, 1996, Osteoclastic giant cell tumor of the pancreas: an immunohistochemical study. Arch Pathol Lab Med 20:306–309
Dworak O, Wittekind C, Koerfgen H, Gall F, 1993, Osteoclastic giant cell tumor of the pancreas. An immunohistochemical study and review of the literature. Pathol Res Pract 198:228–231
Gatteschi B, Saccomanno S, Bartoli F, Salvi S, Liu G, Pugliese V, 1995, Mixed pleomorphic osteoclast-like tumor of the pancreas. Light microscopical, immunohistochemical, and molecular biological studies. Int J Pancreatol 18:169–175
Goldberg R, Michelassi F, Montag A, 1991, Osteoclast-like giant cell tumor of the pancreas: immunophenotypic similarity to giant cell tumor of bone. Hum Pathol 22:618–22
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Machado MAC, Herman P, Montagnini AL, Jukemura J, Leite KRM, Machado MCC, 2001, Benign variant of osteoclast-type giant cell tumor of the pancreas: importance of the lack of epithelial differentiation. Pancreas 22:105–107
Mentes A, Yuce G, 1993, Osteoclast-type giant cell tumor of the pancreas associated with mucinous cystadenoma. Eur J Surg Oncol 19:84–86
Molberg K, Heffes C, Delgado R, Albores-Saavedra J, 1998, Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and periampullary region. Cancer 82:1279–1287
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Shiozawa M, Imada T, Ishiwa N, Rino Y, Hasuo K, Takanashi Y, Nakatani Y, Inayama Y, 2002, Osteoclast-like giant cell tumor of the pancreas. Int J Clin Oncol 7:376–380
Sun A, Ohtsuki Y, Liang S, Sonobe H, Iwata J, FurihataM, Takeuchi T, Qiu Y, Chen B, Watanabe R, Ohmori K, 1998, Osteoclast-like giant cell tumor of the pancreas with metastases to gallbladder and lymph nodes. A case report. Pathol Res Pract 194:587–594
Weidner N, Cote R, Suster S, Weiss L, 2003, Modern Surgical Pathology. Saunders, Philadelphia
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 129
EP 131
DI 10.1007/s12253-008-9053-9
PG 3
ER
PT J
AU Sterlacci, W
Veits, L
Moser, P
Steiner, HJ
Ruscher, S
Jamnig, H
Mikuz, G
AF Sterlacci, William
Veits, Lothar
Moser, Patrizia
Steiner, Hans-Jorg
Ruscher, Sighard
Jamnig, Herbert
Mikuz, Gregor
TI Idiopathic Systemic Amyloidosis Primarily Affecting the Lungs with Fatal Pulmonary Haemorrhage due to Vascular Involvement
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Amyloidosis; Haemorrhage; Pulmonary
ID Amyloidosis; Haemorrhage; Pulmonary
AB A patient who presented with dyspnea and suspected interstitial pulmonary fibrosis suffered a fatal pulmonary haemorrhage with no feasible cause for bleeding. Autopsy revealed abundant amyloid deposits in both lungs with a diffuse alveolar septal distribution pattern. Amyloid was also found in the cardiac interstitium and in many vessel walls. Considering the affected organs and the histological characteristics, the deposits were regarded as light chain-type. Amyloidosis, which is generally an uncommon disease, very rarely affects the lung predominantly. Haemorrhagic diathesis is a known complication in amyloidosis patients, although fatal haemorrhage is rare and has not yet been reported solely of pulmonary origin. This report describes an uncommon case of idiopathic systemic amyloidosis mainly manifesting in the lungs. The diagnosis was established after fatal pulmonary haemorrhage caused by vessel impairment due to additional vascular amyloid deposits.
C1 [Sterlacci, William] Medical University of Innsbruck, Department of Pathology, Mullerstrasse 44, 6020 Innsbruck, Austria.
[Veits, Lothar] Medical University of Innsbruck, Department of Pathology, Mullerstrasse 44, 6020 Innsbruck, Austria.
[Moser, Patrizia] Medical University of Innsbruck, Department of Pathology, Mullerstrasse 44, 6020 Innsbruck, Austria.
[Steiner, Hans-Jorg] Medical University of Innsbruck, Department of Pathology, Mullerstrasse 44, 6020 Innsbruck, Austria.
[Ruscher, Sighard] Hospital Natters, Department for Pneumonology, In der Stille 20, 6161 Natters, Austria.
[Jamnig, Herbert] Hospital Natters, Department for Pneumonology, In der Stille 20, 6161 Natters, Austria.
[Mikuz, Gregor] Medical University of Innsbruck, Department of Pathology, Mullerstrasse 44, 6020 Innsbruck, Austria.
RP Sterlacci, W (reprint author), Medical University of Innsbruck, Department of Pathology, 6020 Innsbruck, Austria.
EM william.sterlacci@i-med.ac.at
CR Lachmann HJ, Hawkins PN, 2006, Amyloidosis and the lung. Chron Respir Dis 3:203–14
Sanchorawala V, 2006, Light-chain, AL, amyloidosis: diagnosis and treatment. Clin J Am Soc Nephrol 1:1331–1341
Howard ME, Ireton J, Daniels F, Langton D, et al., 2001, Pulmonary presentations of amyloidosis. Respirology 6:61–64
Greipp PR, Kyle RA, Bowie EJ, 1981, Factor-X deficiency in amyloidosis: a critical review. Am J Hematol 11:443–450
Yood RA, Skinner M, Rubinow A et al, 1983, Bleeding manifestations in 100 patients with amyloidosis. JAMA 249: 1322–1324
Mumford AD, O'Donnell J, Gillmore JD et al, 2000, Bleeding symptoms and coagulation abnormalities in 337 patients with ALamyloidosis. Br J Haematol 110:454–460
Wright JR, Calkins E, Humphrey RL, 1977, Potassium permanganate reaction in amyloidosis. A histologic method to assist in differentiating forms of this disease. Lab Invest 6:274–281
Browning MJ, Banks RA, Tribe CR et al, 1985, Ten years’ experience of an amyloid clinic–a clinicopathological survey. Q J Med 54:213–227
Gillmore JD, Hawkins PN, 1999, Amyloidosis and the respiratory tract. Thorax 54:444–451
Berk JL, Keane J, Seldin DC et al, 2003, Persistent pleural effusions in primary systemic amyloidosis: etiology and prognosis. Chest 124:969–977
Lee HM, Naor J, DeAngelis D et al, 2000, Primary localized conjunctival amyloidosis presenting with recurrence of subconjunctival hemorrhage. Am J Ophthalmol 129:245–247
Rapoport M, Yona R, Kaufman S et al, 1994, Unusual bleeding manifestations of amyloidosis in patients with multiple myeloma. Clin Lab Haematol 16:349–353
Alwitry A, Brackenbury ET, Beggs FD et al, 2001, Vascular amyloidosis causing spontaneous mediastinal haemorrhage with haemothorax. Eur J Cardiothorac Surg 20:871–873
Shaheen NA, Salman SD, Nassar VH, 1975, Fatal bronchopulmonary hemorrhage due to unrecognized amyloidosis. Arch Otolaryngol 101:259–261
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 133
EP 136
DI 10.1007/s12253-008-9066-4
PG 4
ER
PT J
AU Rekhi, B
Kumar, R
Menon, S
Medhi, S
Desai, BS
AF Rekhi, Bharat
Kumar, Rajiv
Menon, Santosh
Medhi, Seema
Desai, B Sangeeta
TI Calvarial Metastasis of a Renal Cell Carcinoma, Mimicking a Primary Alveolar Soft Part Sarcoma, in a Young Girl—a Rare Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Calvarial; Skull metastases; Renal cell carcinoma; Alveolar soft part sarcoma; CD10 staining
ID Calvarial; Skull metastases; Renal cell carcinoma; Alveolar soft part sarcoma; CD10 staining
AB Renal cell carcinoma (RCC) is characterized by an unpredictable clinical behavior. It has a tendency for early metastasis, which, at times is the initial presentation and therein poses a diagnostic challenge. We present a rare case of a disseminated RCC in a 15-year-old girl, who primarily presented with an occipital soft tissue mass. Computed tomography (CT) of the head revealed a soft tissue mass in the scalp, eroding the occipital bone and extending intracranially. Biopsy examination showed overlapping features of an alveolar soft part sarcoma (ASPS) and a RCC. Immunohistochemistry (IHC) showed diffuse positivity for CD10 and focal positivity for vimentin. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. The patient was recommended a clinical ‘work-up’ to rule out a possible primary in the kidneys. Her CT scan abdomen unraveled a large, lobulated, heterogeneous cystic mass, involving the middle and upper pole of the left kidney. Diagnosis of a metastatic RCC was ascertained. The present case represents a rare manifestation of a RCC metastasizing at an unusual location i.e. calvarium in the youngest patient known, so far and masquerading a primary ASPS. It also highlights the value of clinico-patho-radiological correlation, including CD10 as a useful IHC marker in diagnosing a RCC in young patients, especially when histopathological features overlap with ASPS.
C1 [Rekhi, Bharat] Tata Memorial Hospital, Department of Pathology, Dr Ernest Borges Road, Parel, 400012 Mumbai, India.
[Kumar, Rajiv] Tata Memorial Hospital, Department of Pathology, Dr Ernest Borges Road, Parel, 400012 Mumbai, India.
[Menon, Santosh] Tata Memorial Hospital, Department of Pathology, Dr Ernest Borges Road, Parel, 400012 Mumbai, India.
[Medhi, Seema] Tata Memorial Hospital, Department of RadiodiagnosisMumbai, India.
[Desai, B Sangeeta] Tata Memorial Hospital, Department of Pathology, Dr Ernest Borges Road, Parel, 400012 Mumbai, India.
RP Rekhi, B (reprint author), Tata Memorial Hospital, Department of Pathology, 400012 Mumbai, India.
EM rekhi.bharat@gmail.com
CR Pantuck AJ, Zisman A, Belldegrun AS, 2001, The changing natural history of renal cell carcinoma. J Urol 166:1611– 1623
Bruder E, Passera O, Harms D, Leuschner I, Ladanyi M, Argani P, Eble JN, Struckmann K, Schraml P, Moch H, 2004, Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am J Surg Pathol 28:1117–1132
Renshaw AA, Granter SR, Fletcher JA, Kozakewich HP, Corless CL, Perez-Atayde AR, 1999, Renal cell carcinomas in children and young adults: increased incidence of papillary architecture and unique subtypes. Am J Surg Pathol 23:795–802
Sunita, Kapila K, Singhal RM, Verma K, 1991, Fine needle aspiration diagnosis of an unusual presentation of metastatic renal cell carcinoma, letter). Acta Cytol 35:260–261
Wahner-Roedler L, Sebo T, 1997, Renal cell carcinoma; diagnosis based on metastatic manifestations, case report). Mayo Clin Proc 72:935–941
Koutnouyan HA, Rumore GJ, Kahn JM, 1998, Skull metastasis from renal cell carcinoma. Case report and literature review. Ann Otol Rhinol Laryngol 107:598–602
Gaetani P, Di Ieva A, Colombo P, Tancioni F, Aimar E, Debernardi A, Baena RR, 2005, Calvarial metastases as clinical presentation of renal cell carcinoma: report of two cases and review of the literature. Clin Neurol Neurosurg 107:329–333
De Vos C, Gerard JM, Decat M, Gersdorff M, 2005, Metastatic renal cell carcinoma to the temporal bone: case report. B-ENT 1:43–46
Yeh HC, Yang SF, Ke HL, Lee KS, Huang CH, Wu WJ, 2007, Renal cell carcinoma presenting with skull metastasis: a case report and literature review. Kaohsiung J Med Sci 23:475–479
Forbes GS, McLeod RA, Hattery RR, 1977, Radiographic manifestations of bone metastases from renal carcinoma. AJR Am J Roentgenol 129:61–66
Avery AK, Beckstead J, Renshaw AA, Corless CL, 2000, Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 24(2):203–210
Argani P, Antonescu CR, Illei PB et al, 2001, Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159:179–192
Rackley R, Novick A, Klein E, Bukowski R, McLain D, Goldfarb D, 1994, The impact of adjuvant nephrectomy on multi-modality treatment of metastatic renal cell carcinoma. J Urol 152:1399– 1403
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 137
EP 141
DI 10.1007/s12253-008-9097-x
PG 5
ER
PT J
AU Hortobagyi, T
Alhakim, A
Biedrzycki, O
Djurovic, V
Rawal, J
Al-Sarraj, S
AF Hortobagyi, Tibor
Alhakim, Ali
Biedrzycki, Olaf
Djurovic, Vesna
Rawal, Jeewan
Al-Sarraj, Safa
TI Cysticercosis of the Fourth Ventricle Causing Sudden Death: A Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cysticercosis; Neurocysticercosis; Sudden death; Taenia solium
ID Cysticercosis; Neurocysticercosis; Sudden death; Taenia solium
AB A 15 years old girl of African origin was admitted with a history of headaches and a generalised tonic seizure. Her clinical examination including fundoscopy was normal. She claimed she had been assaulted. Within a few hours of her admission she was found dead in her bed during the ward round. Cardiopulmonary resuscitation was unsuccessful. At post-mortem, the major organs showed no pathological changes and neck dissection showed no abnormality. Neuropathological examination after formalin fixation revealed a cystic lesion in the fourth ventricle, ependymitis and acute hydrocephalus. Histology showed parts of the parasite Taenia solium and the diagnosis was neurocysticercosis. This case highlights the need for forensic and general pathologists as well as forensic medical examiners and paediatricians to be aware of neurocysticercosis as a possible cause of sudden death in the presence of normal clinical findings and negative autopsy, especially in patients from Asian, African or South American countries. As cysticercosis is the commonest cause of seizures in the developing world, neurocysticercosis needs to be considered as a cause of sudden and unexpected death in any patient with a history of headaches and/or seizures.
C1 [Hortobagyi, Tibor] King’s College Hospital, Clinical Neuropathology, Denmark Hill, SE5 9RS London, UK.
[Alhakim, Ali] East Surrey Hospital, Department of HistopathologySurrey, UK.
[Biedrzycki, Olaf] Royal London Hospital, Institute of PathologyLondon, UK.
[Djurovic, Vesna] Forensic Pathology ServicesLondon, UK.
[Rawal, Jeewan] BHR NHS Trust, Oldchurch HospitalRomford, Essex, UK.
[Al-Sarraj, Safa] King’s College Hospital, Clinical Neuropathology, Denmark Hill, SE5 9RS London, UK.
RP Al-Sarraj, S (reprint author), King’s College Hospital, Clinical Neuropathology, SE5 9RS London, UK.
EM safa.al-sarraj@kch.nhs.uk
CR Esberg G, Reske-Nielsen E, 1988, Sudden death from cerebral cysticercosis. Scand J Infect Dis 20:679–684
Bent Hamida M, Moulonguet A, Romano P, Gray F, 1993, Confrontation at the Salpetriere hospital. May 1991 Cephalagia developing in depressive background and sudden death in a 26 year old woman. Rev Neurol, Paris, 149:362–366
Ndhlovu CE, 1997, An uncommon presentation of cysticercosis. Cent Afr J Med 43:207–209
DeGiorgio CM, Houston I, Oviedo S, Sorvillo F, 2002, Deaths associated with cysticercosis. Report of three cases and review of the literature. Neurosurg Focus 12:e2
Verma SK, Agarwal BB, Agarwal G, 1998, Sudden death in neurocysticercosis by trauma. Forensic Sci. Int. 95:23–26
Rao KR, Lessing D, 2003, Neurocysticercosis in West London. Arch Dis Child 88:471
DeGiorgio CM, Medina MT, Duron R, Zee C, Escueta SP, 2004, Neurocysticercosis. Epilepsy Curr 4:107–111
Del Brutto OH, 2005, Neurocysticercosis. Semin Neurol 25:243–251
Rosenfeld E, 2003, Neurocysticercosis. Update Pediatr Infect Dis J 22:181–182
Oeberst JL, Barnard JJ, Bigio EH, Prahlow JA, 2002, Neurocysticercosis. Am J Forensic Med. Pathol, 2002, 23:31–35
Rajshekhar V, Joshi DD, Doanh NQ, van De N, Xiaonong Z, 2003, Taenia solium taeniosis/cysticercosis in Asia: epidemiology, impact and issues. Acta Trop 87:53–60
White AC Jr, 1997, Neurocysticercosis: a major cause of neurological disease worldwide. Clin. Infect. Dis. 24:101–115
Gubbay AD, Brophy BP, Henley S, Sage M, 1998, Neurocysticerosis. J Clin Neurosci 5:203–207
Pitella JEM, 1997, Neurocysticercosis. Brain Pathol 7:681–693
Deb KP, Carpio A, Sander JWAS, 2000, Neurocysticercosis and epilepsy in developing countries. J. Neurol. Neurosurg. Psychiatry 68:137–143
Goodyear M, Voyvodic F, Brophy B, Sage M, 1997, Spinal cysticercosis. J. Clin. Neurosci 4:25–27
De Souza Queiroz L, Filho AP, Callegaro D, De Faria LL, 1975, Intramedullary cysticercosis. Case report, literature review and comments on pathogenesis. J Neurol Sci 26:61–70
Adhisivam B, 2004, Starry sky: multiple neurocysticercosis. Arch Dis Child Educ Pract 89:ep75
Biedrzycki O, Hortobagyi T, Alhakim A, Hunt N, Djurovic V, Al-Sarraj S, 2006, Sudden deaths caused by intraventricular cysts, neuropathol. Appl. Neurobiol 32:240 [Abstract]
Jarquin-Valdivia AA, Rich AT, Yarbrough JL, Thompson RC, 2005, Intraventricular colloid cyst, hydrocephalus and neurogenic stunned myocardium. Clin. Neurol. Neurosurg. 107:361–365
Garcia HH, Evans CA, Nash TE, Takayanagui OM, White AC Jr, Botero D, RajshekharV, Tsang VC, Schantz PM, Allan JC, Flisser A, Correa D, Sarti E, Friedland JS,Martinez SM, Gonzalez AE, Gilman RH, Del Brutto OH, 2002, Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 15:747–756
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 143
EP 146
DI 10.1007/s12253-008-9098-9
PG 4
ER
PT J
AU Suranyi, A
Bito, T
Vajda, Gy
Kaiser, L
Gaspar, G
Katona, M
Szabo, J
Pal, A
AF Suranyi, Andrea
Bito, Tamas
Vajda, Gyorgy
Kaiser, Laszlo
Gaspar, Gabor
Katona, Marta
Szabo, Janos
Pal, Attila
TI Unusual Clinical History of a Male Infant with Edwards Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dysgenesis of corpus callosum; Edwards syndrome; Oesophageal atresia; Renal agenesis; Ultrasound
ID Dysgenesis of corpus callosum; Edwards syndrome; Oesophageal atresia; Renal agenesis; Ultrasound
AB Edwards syndrome (trisomy of chromosome 18) is generally characterized by the disorders of central nervous system, as well as the musculoskeletal and genitourinary systems. In majority of the cases with trisomy 18 the following malformations can be found: ventricular septal defect, horseshoe kidneys, oesophageal atresia, omphalocele, facial clefts, diaphragmatic hernias and genital hypoplasia. We report a male patient with Edwards syndrome. The boy had a partial agenesis of corpus callosum, oesophageal atresia with tracheo-oesophageal fistula, renal agenesis, ventricular septal defect, Dandy-Walker cyst and low-set malformed ears. The first three features are unique based on previous literature reports on trisomy 18. This report allows a further delineation of the trisomy 18 syndrome.
C1 [Suranyi, Andrea] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Bito, Tamas] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Vajda, Gyorgy] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Kaiser, Laszlo] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Gaspar, Gabor] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Katona, Marta] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Szabo, Janos] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
[Pal, Attila] University of Szeged, Department of Obstetrics and Gynaecology, Semmelweis u. 1, 6725 Szeged, Hungary.
RP Pal, A (reprint author), University of Szeged, Department of Obstetrics and Gynaecology, 6725 Szeged, Hungary.
EM PALATTILA@obgyn.szote.u-szeged.hu
CR Inbar D, Halpern GJ, Weitz R et al, 1997, Agenesis of the corpus callosum in a mother and son. Am J Med Genet 69:152–154
Lynn RB, Buchanan DC, Fenichel GM et al, 1980, Agenesis of the corpus callosum. Arch Neurol 37:444–445
Naiman J, Fraser FC, 1955, Agenesis of the corpus callosum; a report of two cases in siblings. AMA Arch Neurol Psychiatry 74:182–185
Naritomi K, Chinen Y, Asato Y, 1997, Agenesis of corpus callosum in three sibs. Jpn J Hum Genet 42:539–541
Pineda M, Gonzalez A, Fabregues I et al, 1984, Familial agenesis of the corpus callosum with hypothermia and apneic spells. Neuropediatrics 15:63–67
Pirola B, Bortotto L, Giglio S et al, 1998, Agenesis of the corpus callosum with Probst bundles owing to haploinsufficiency for a gene in an 8 cM region of 6q25. J Med Genet 35:1031–1033
Shapira Y, Cohen T, 1973, Agenesis of the corpus callosum in two sisters. J Med Genet 10:266–269
Tepper R, Zalel Y, Gaon E et al, 1996, Antenatal ultrasonographic findings differentiating complete from partial agenesis of the corpus callosum. Am J Obstet Gynecol 174:877–878
Lockwood CJ, Ghidini A, Aggarwal R et al, 1988, Antenatal diagnosis of partial agenesis of the corpus callosum: a benign cause of ventriculomegaly. Am J Obstet Gynecol 159:184–186
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Franco I, Kogan S, Fisher J et al, 1993, Genitourinary malformations associated with agenesis of the corpus callosum. J Urol 149: 1119–1121
Gonzalez-Zamora JF, Villegas-Alvarez F, 2005, Esophageal atresia and chromosomal abnormalities in a Mexican children population: descriptive analysis. Cir Pediatr 18:196–199
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Kamnasaran D, 2005, Agenesis of the corpus callosum: lessons from humans and mice. Clin Invest Med 28:267–282
Curnes JT, Laster DW, Koubek TD et al, 1986, MRI of corpus callosal syndromes. AJNR Am J Neuroradiol 7:617–622
Utsunomiya H, Ogasawara T, Hayashi T et al, 1997, Dysgenesis of the corpus callosum and associated telencephalic anomalies: MRI. Neuroradiology 39:302–310
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2009
VL 15
IS 1
BP 147
EP 152
DI 10.1007/s12253-008-9023-2
PG 6
ER
PT J
AU Zhou, Chj
Zhang, Qh
Zhang, Tg
Sun, Shz
Li, H
Wang, Y
Liu, Zy
AF Zhou, Cheng-jun
Zhang, Qing-hui
Zhang, Ting-guo
Sun, Shan-zhen
Li, Hong
Wang, Yan
Liu, Zhi-yan
TI Expression of ER, Ki-67 and CylinD1 in the Pre-cancerous Breast of Chinese Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pre-cancerous lesions; Breast; ER; Ki-67; CyclinD1
ID Pre-cancerous lesions; Breast; ER; Ki-67; CyclinD1
AB To investigate the expression and association of ER, Ki-67 and cyclinD1 in usual ductal hyperplasia(UDH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ(DCIS) in the breast. The study included 56 cases of precancerous lesions which were surgically excised at Qi Lu Hospital of Shangdong University. Immunohistochemistry was used to determine the expression of ER, Ki-67 and cyclinD1 and double-labelling immunofluorescence technique was used to observe the coexpression of ER and Ki-67. The expression and distribution of ER-positive cells were significantly different in UDH, ADH and DCIS. The ER-positive cells were much more in UDH than in normal TDLUs (terminal duct lobular units). The distribution of ER-positive cells interspersed amid ER-negative cells within UDH. However , the ER positive cells showed marked increases in ADH and low grade nuclear DCIS (P<0.05), distributing in almost all constituent cells. The expression of ki-67 and cyclinD1 were significantly different between UDH and DCIS (P<0.05) , and a positive correlation was found between expression of Ki-67 and morphological classification of pre-cancerous lesions (r=0.3522, P<0.05) as well as cyclinD1 (r=0.3901, P<0.05). Double-labelling immunofluorescence showed that there was no coexpression of ER and Ki-67 in normal breast tissue. The coexpression of the two markers was found in ADH and increased in DCIS. Overexpression of ER, Ki-67 and cyclinD1 significantly accompanies the transition of normal cells and UDH to ADH and DCIS. The coexpression of ER and ki-67 may present the early change in carcinogenesis of breast cancer.
C1 [Zhou, Cheng-jun] The Second Hospital of Shandong University, 250033 Jinan, China.
[Zhang, Qing-hui] Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
[Zhang, Ting-guo] Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
[Sun, Shan-zhen] Shandong University, Stomatology Hospital, 250012 Jinan, China.
[Li, Hong] Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
[Wang, Yan] Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
[Liu, Zhi-yan] Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
RP Zhang, Qh (reprint author), Shandong University, Qilu Hospital, Department of Pathology, 250012 Jinan, China.
EM chengjunzhou@eyou.com
CR Yager JD, Davidson NE, 2006, Estrogen carcinogenesis in breast cancer. N Engl J Med 354:270–282
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Kontos M, Nikolopoulou M, Trafalis DT et al, 2005, The effect of an estrone D-lactam steroid ester derivative on breast cancer cells and its predicted binding interactions with the ligand binding domain of estrogen receptor-alpha. Oncol Res 16:129–142
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 153
EP 158
DI 10.1007/s12253-008-9100-6
PG 6
ER
PT J
AU Egyed, Zs
Jaray, B
Kulka, J
Pentek, Z
AF Egyed, Zsofia
Jaray, Balazs
Kulka, Janina
Pentek, Zoltan
TI Triple Test Score for the Evaluation of Invasive Ductal and Lobular Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lobular; Ductal; Breast cancer; Sum-score diagnosis; Triple test; Symptomless
ID Lobular; Ductal; Breast cancer; Sum-score diagnosis; Triple test; Symptomless
AB The aim of our study was to compare the preoperative sum score diagnostics of invasive ductal and lobular cancers using three or four diagnostic methods. The novelty of this study is the examination of this phenomenon based on sum score, no such papers can be found in the literature. Ductal cancers have higher score values indicating easier diagnostics, but the difference in distribution of the scores was significant ( p=0.0086) only in case of the triple-test. The score values give appropriate opportunity to create their order of diagnostic power which was the same by both histologic types and in their subgroups with low sum-score: the strongest was cytology, followed by mammography, ultrasound and physical examination. No significant difference was found between the two histologic group in their mammographic appearances—stellate, circumscribed, assymmetric distortion or microcalcification (p=0.0694). In low score subgroup besides the occult forms, structural distortion and indeterminate microcalcifications overweighed the stellate and circumscribed lesions typical for the whole groups. In symptomless cases of both histologic groups only one strongly malignant diagnostic test result warrants the right diagnosis. Summarizing the score distribution of the results in case of four diagnostic tools the higher scores—indicating malignancy—were more frequent in the ductal group compared to the lobular ones. Extra attention has to be paid to rare radiomorphologic appearances and to the most deterministic examination, namely cytology.
C1 [Egyed, Zsofia] MaMMa Egeszsegugyi Rt, Kapas u. 29, 1023 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Pentek, Zoltan] MaMMa Egeszsegugyi Rt, Kapas u. 29, 1023 Budapest, Hungary.
RP Egyed, Zs (reprint author), MaMMa Egeszsegugyi Rt, 1023 Budapest, Hungary.
EM egyed.zsofia@t-online.hu
CR Tot T, 2003, The diffuse type of invasive lobular carcinoma of the breast: morphology and prognosis. Virchows Arch 43:718–724
Martinez V, Azzopardi JG, 1979, Invasive lobular carcinoma of the breast: incidence and variants. Histopathology 493:467–488
Li CI, Anderson BO, 2003, Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 19(289):1421–1424
Adler OB, Engel A, 1990, Invasive lobular carcinoma. Mammographic pattern. Rofo 152:460–462
Ashikari R, Huvos AG, Urban JA, 1973, Infiltrating lobular carcinoma of the breast. Cancer 31:110–116
Broet P, de la Rochefordiere A, Scholl SM et al, 1995, Contralateral breast cancer:annual incidence and risk parameters. J Clin Oncol 13:1578–1583
Silverstein MJ, Lewinsky BS, Waisman Gierson ED et al, 1994, Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma. Cancer 73:1673–1677
Biglia N, Mariani L, Sgro L et al, 2007, Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications of diagnosis, surgical and medical treatment. Endocr Relat Cancer 14:549–567
Toikkanen S, Pylkannen L, Joensu H, 1997, Invasive lobular carcinoma of the breast has better short-term and long-term survival than invasive ductal carcinoma. Br J Cancer 78:1234–1240
Hermansen C, Poulsen H, Jensen J et al, 1984, Palpable breast tumours: “triple diagnosis” and operative strategy. Acta Chir Scand 150:625–628
Azzarelli A, Guzzon A, Pilotti S et al, 1983, Accuracy of breast cancer diagnosis by physical and radiologic and cytologic combined examinations. Tumori 69:137–141
Irwing L, Macaskill P, Houssami N, 2002, Evidence relevant to the investigation of breast symptoms:the triple test. Breast 11:215–220
Morris AM, Flowers CR, Morris KT et al, 2003, Comparing the cost-effectiveness of the triple test score to traditional methods for evaluating palpable breast masses. Med Care 41:962–971
Morris KT, Pommier RF, Morris A et al, 2001, Usefulness of triple test score for palpable breast masses. Arch Surg 136:1008– 1012
Vetto JT, Pommier RF, Schmidt WA et al, 1995, Use of “triple test” for palpable breast lesion yields high diagnostic accuracy and cost savings. Am J Surg 169:519–522
Houssami N, Irwing L, Simpson J et al, 2003, Sydney breast imaging accuracy study: comparative sensitivity and specificity of mammography and sonography in young women with symptoms. AJR 180:935–940
Morris KT, Vetto JT, Petty JK et al, 2002, A new score for the evaluation of palpable breast masses in women under age 40. Am J Surg 184:346–347
Houssami N, Irwing L, Loy C, 2002, Accuracy of combines breast imaging in young women. Breast 11:36–40
Kuhl CK, Schrading S, Weigel S et al, 2005, The EVA trial: evaluation of the efficacy of diagnostic methods, mammography, ultrasound, MRI, in the secondary and tertiary prevention of familiar breast cancer. Preliminary results after the first half of the study period. Rofo 177:818–827
Egyed Z, Jaray B, Pentek Z, 2006, Invasive lobular breast cancer: pitfall for the radiologist. Orv Hetil 5:219–226
American College of Radiology, 1995, Breast imaging reporting and data system, BI-RADS), 2nd edn. American College of Radiology, Reston
Vincze I, Varbanova M, 1993, Non-parametric mathematical statistics. Theory, and practices, 1st edn. Akad. Kiado, Budapest, in Hungarian)
Kemeny S, Deak A, Lakne Komka K et al, 2004, Statistical analysis using Statistica, 1st edn. Muegyetemi Kiado, Budapest, in Hungarian)
Sartre-Garu X, Jouve M, Asselain B et al, 1994, Infiltrating lobular carcinoma of the breast Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer 73:1673–1677
Newstead GM, Baute PB, Toth HK, 1992, Invasive lobular and ductal carcinoma: mammographic findings and stage at diagnosis. Radiology 184(3):623–627
Christopher IL, Anderson BO, Porter P et al, 2000, Changing incidence rate of invasive lobular breast carcinoma among older women. Cancer 88:2561–2569
Krecke KN, Gisvold JJ, 1993, Invasive lobular carcinoma of the breast: mammographic findings and extent of disease in 184 patients. AJR 88:957–960
Bazzocchi M, Facecchia I, Zulani C et al, 2000, Diagnostic imaging of lobular carcinoma of the breast: mammographic, ultrasonographic and MR findings. Radiol Med 100:436– 443
Foote FW Jr, Stewart FW, 1946, A histologic classification of carcinoma of the breast. Surgery 19:74–99
Langmar Z, Orosz Z, 1999, Clinico-pathology of lobular breast cancer. Orv Hetil 140(20):1099–1102
Sastre-Garau X, Jouve M, 1996, Infiltrating lobular carcinoma of the breast. Cancer 1:113–120
Silverstein MJ, Lewinsky BS, 1994, Infiltrating lobular carcinoma. Cancer 73:673–77
Steinberg JL, Trudeau ML, Ryder DE et al, 1996, Combined fine-needle aspiration, physical examination and mammography in the diagnosis of palpable breast massses: their relation to outcome for women with primary breast cancer. C J Surg 39: 302–311
Morris A, Pommier RF, Schmidt WA et al, 1998, Accurate evaluation of palpable breast masses by the triple test score. Arch Surg 133:390–394
Mansoor I, Zahrani I, 2002, Analysis of inconclusive breast FNA by triple test. J Pak Med Assoc. 52:25–29
Fenton JJ, Barton MB, Geiger AM et al, 2005, Screening clinical breast examination:how often does it miss lethal breast cancer. J Natl Cancer Inst Monogr 35:67–71
Gill G, Luke C, Roder D, 2006, Prognostic importance of palpability as a feature of screen-detected breast cancers. JMed Screen 13:98–101
Knight JA, Libstug AR, Moravan Vet al, 1998, An assessment of the influence of clinical breast examination reports on the interpretation of mammograms in a breast screening program. Breast Cancer Res Treat 48:65–71
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Bartella L, Liberman L, Morris EA et al, 2006, Nonpalpable mammographically occult invasive breast cancers detected by MRI. AJR 186:865–870
Mathieu I, Mazy S, Willemart B et al, 2005, Inconclusive triple diagnosis in breast cancer imaging: is there a place for scintimammography. J Nucl Med 46:1574–1581
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 159
EP 166
DI 10.1007/s12253-008-9083-3
PG 8
ER
PT J
AU Mannweiler, S
Amersdorfer, P
Trajanoski, S
Terrett, AJ
King, D
Mehes, G
AF Mannweiler, Sebastian
Amersdorfer, Peter
Trajanoski, Slave
Terrett, A Jonathan
King, David
Mehes, Gabor
TI Heterogeneity of Prostate-Specific Membrane Antigen (PSMA) Expression in Prostate Carcinoma with Distant Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Antibody; Immunohistochemistry; Therapy
ID Prostate cancer; Antibody; Immunohistochemistry; Therapy
AB Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in advanced stage prostate adenocarcinomas. As a novel target for in vivo prognostic and therapeutic approaches, the distribution pattern of PSMA in primary and metastatic tumors is of significant interest. In this study we addressed the cellular distribution and heterogeneity of PSMA expression. Paraffinembedded sections of 51 patients with primary prostate carcinoma and distant metastases were evaluated. Immunohistochemistry was used to determine the cellular localization, staining intensity and positive cell fraction which were related to tumor type and growth pattern. We demonstrated differences in the intracellular localization of the PSMA immunostaining which seem to be related to the tumor differentiation pattern. A significant number of the primary tumors (7/51) and metastases (6/51) presented with highly heterogeneous PSMA expression and in further 2 primary, and 8 metastatic tumors the staining was in the negative range (<10% positive tumor cells). A direct correlation between histological parameters and PSMA expression could not be demonstrated. Our findings clearly support the feasibility but also direct to potential failures of PSMA-targeted in vivo diagnostic and therapeutic approaches in prostate cancer patients with distant metastasis.
C1 [Mannweiler, Sebastian] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, 8036 Graz, Austria.
[Amersdorfer, Peter] Oridis-Biomed GMBH, Stiftingtalgasse 3-5, 8010 Graz, Austria.
[Trajanoski, Slave] Graz University of Technology, Christian Doppler Laboratory for Genomics and Bioinformatics, Petersgasse 14, 8010 Graz, Austria.
[Terrett, A Jonathan] Medarex Inc., 521 Cottonwood Drive, 95035 Milpitas, CA, USA.
[King, David] Medarex Inc., 521 Cottonwood Drive, 95035 Milpitas, CA, USA.
[Mehes, Gabor] Oridis-Biomed GMBH, Stiftingtalgasse 3-5, 8010 Graz, Austria.
RP Mannweiler, S (reprint author), Medical University of Graz, Department of Pathology, 8036 Graz, Austria.
EM sebastian.mannweiler@meduni-graz.at
CR Chang SS, 2004, Overview of prostate-specific membrane antigen. Rev Urol 6:S13–S16
Pinto JT, Suffoletto BP, Berzin TM et al, 1996, Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res 2:1445–1451
Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP, 1998, Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82:2256–2261
Perner S, Hofer MD, Kim R, Shah RB, Li H, Moller P, Hautmann RE, Gschwendt JE, Kuefer R, Rubin MA, 2007, Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol 38:696–701
Horoszewicz JS, Kawinski E, Murphy GP, 1987, Monoclonal antibodies to a new antigenic marker in epithelial cells and serum of prostatic cancer patients. Anticancer Res 7:927–936
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Silver DA, Pellicer I, Fair WL et al, 1997, Prostate-specific membrane antigen expression in normal and malignant human tissue. Clin Cancer Res 3:81–85
Chang S, O’Keefe DS, Bacich DJ, Reuter VE, Heston WD Gaudin PB, 1999, Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res 5:2674–2681
Wright GL, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer PF, Moriarty R, 1996, Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 48:326–334
Gleason DF, 1977, Histologic grading and clinical staging of prostatic carcinoma. In: Tannebaum M, ed, Urologic pathology: the prostate. Lea & Febiger, Philadelphia, pp 171–197
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Douglas G. Altman: Practical Statistics for Medical Research Chapman & Hall/CRC 1 edition, November 22, 1990)
Bander NH, 2006, Technology insight: monoclonal antibody imaging of prostate cancer. Nat Clin Pract Urol 3(4):216–225
Sodee DB, Sodee AE, Bakale G, 2007, Synergistic value of single-photon emission computed tomography/computed tomography fusion to radioimmunoscintigraphic imaging of prostate cancer. Semin Nucl Med 37(1):17–28
Elsasser-Beile U, Wolf P, Gierschner D, Buhler P, Schultze- Seemann W, Wetterauer U, 2006, A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancer. Prostate 66(13):1359–1370
Ross JS, Sheehan CHE, Fisher HAG, Kaufman RP, Kaur P, Gray K, Webb I, Gray GS, Mosher R, Kallakury BVS, 2003, Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res 9:6357–6362
Zhigang Z, Wenly S, 2004, Prostate stem cell antigen, PSCA, expression in human prostate cancer tissue and its potential role in prostate carcinogenesis and progression of prostate cancer. W J Surg Oncol 2:1–13
Buhler P, Wolf P, Gierschner D, Schabel I, Katzenwadel A, Schultze-Seemann W, Wetterauer U, Tacke M, Swamy M, Schamel WW, Elsasser-Beile U, 2008, A bispecific diabody directed against prostate-specific membrane antigen and CD33 induces T-cell mediated lysis of prostate cancer cells. Can Immunol Immunother 57(1):43–52
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 167
EP 172
DI 10.1007/s12253-008-9104-2
PG 6
ER
PT J
AU Giaginis, TC
Vgenopoulou, S
Tsourouflis, SG
Politi, NE
Kouraklis, PG
Theocharis, ES
AF Giaginis, T Constantinos
Vgenopoulou, Stephanie
Tsourouflis, S Gerasimos
Politi, N Ekaterini
Kouraklis, P Gregorios
Theocharis, E Stamatios
TI Expression and Clinical Significance of Focal Adhesion Kinase in the Two Distinct Histological Types, Intestinal and Diffuse, of Human Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clinicopathological parameters; Diffuse; Focal adhesion kinase; Gastric cancer; Immunohistochemistry; Intestinal; Patients’ survival
ID Clinicopathological parameters; Diffuse; Focal adhesion kinase; Gastric cancer; Immunohistochemistry; Intestinal; Patients’ survival
AB Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression and metastasis. The aim of this study was to assess the clinical significance of FAK expression in the two distinct histological types of human gastric neoplasia. FAK expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma cases, 30 intestinal and 36 diffuse type, and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients’ survival. In intestinal type carcinomas, enhanced FAK expression was significantly associated with increased tumor proliferative capacity (P=0.012). In diffuse type carcinomas, FAK staining intensity was significantly correlated with tumor size (P=0.026) and disease stage (P=0.024), presenting also a borderline association with nodal status (P=0.053). In diffuse type carcinomas, enhanced FAK expression was significantly associated with longer overall survival times (log-rank test, P=0.014), being also identified as an independent prognostic factor in multivariate analysis (Cox regression, P=0.016). In contrast, patients with intestinal type tumors and enhanced FAK expression were characterized by shorter overall survival times, without though reaching statistical significance (log-rank test, P=0.092). The current data support evidence that FAK protein may be considered as a diagnostic and prognostic marker in gastric neoplasia. Further studies conducted on larger clinical samples and highlighting on the distinct impact of the two histological types are warranted to delineate the clinical significance of FAK protein in gastric neoplasia.
C1 [Giaginis, T Constantinos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias street, Goudi, GR11527 Athens, Greece.
[Vgenopoulou, Stephanie] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias street, Goudi, GR11527 Athens, Greece.
[Tsourouflis, S Gerasimos] University of Athens, Medical School, Second Department of Propedeutic SurgeryAthens, Greece.
[Politi, N Ekaterini] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias street, Goudi, GR11527 Athens, Greece.
[Kouraklis, P Gregorios] University of Athens, Medical School, Second Department of Propedeutic SurgeryAthens, Greece.
[Theocharis, E Stamatios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias street, Goudi, GR11527 Athens, Greece.
RP Theocharis, ES (reprint author), University of Athens, Medical School, Department of Forensic Medicine and Toxicology, GR11527 Athens, Greece.
EM theocharis@ath.forthnet.gr
CR Lipfert L, Haimovich B, Schaller MD, Cobb BS, Parsons JT, Brugge JS, 1992, Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J Cell Biol 119:905–912
Zachary I, Sinnett-Smith J, Rozengurt E, 1992, Bombesin, vasopressin, and endothelin stimulation of tyrosine phosphorylation in Swiss 3T3 cells. Identification of a novel tyrosine kinase as a major substrate. J Biol Chem 267:19031–19034
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Cary LA, Chang JF, Guan JL, 1991, Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. J Cell Sci 109:1787–1794
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Levy P, Robin H, Kornprobst M, Capeau J, Cherqui G, 1989, Enterocytic differentiation of human Caco-2 cell line correlates with alterations in integrin signaling. J Cell Physiol 177:618–627
Xu LH, Owens LV, Sturge GC, Yang X, Liu ET, Craven RJ, Cance WG, 1996, Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells. Cell Growth Differ 7:413–418
Chatzizacharias NA, Kouraklis G, Theocharis S, 2008, Clinical significance of FAK expression in human neoplasia. Histol Histopathol 23:629–650
Chatzizacharias NA, Kouraklis G, Theocharis S, 2007, Focal adhesion kinase: a promising target for anticancer therapy. Exp Opin ther Targets 11:1315–1328
Chatzizacharias NA, Kouraklis G, Theocharis S, 2008, Disruption of FAK signaling: A side mechanism in cytotoxicity. Toxicology 245:1–10
Iravani S, Mao W, Fu L, Karl R, Yeatman T, Jove R, Coppola D, 1998, Elevated c-Src protein expression is an early event in colonic neoplasia. Lab Invest 78:365–371
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Theocharis SE, Kouraklis GP, Kakisis JD, Kanelli HG, Apostolakou FE, Karatzas GM, Koutselinis AS, 2003, Focal adhesion kinase expression is not a prognostic predictor in colon adenocarcinoma patients. Eur J Surg Oncol 29:571–574
Furuyama K, Ryuchiro D, Tomohiko M, Toyoda E, Ito D, Kami K, Koizumi M, Kida A, Kawaguchi Y, Fujimoto K, 2006, Clinical significance of focal adhesion kinase in resectable pancreatic cancer. World J Surg 30:219–226
Fuji T, Koshikawa K, Nomoto S, Okochi O, Kaneko T, Inoue S, Yatabe Y, Takeda S, Nakao A, 2004, Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor. J Hepatol 41:104–111
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 173
EP 181
DI 10.1007/s12253-008-9120-2
PG 9
ER
PT J
AU Hritz, I
Gyorffy, H
Molnar, B
Lakatos, G
Sipos, F
Pregun, I
Juhasz, M
Pronai, L
Schaff, Zs
Tulassay, Zs
Herszenyi, L
AF Hritz, Istvan
Gyorffy, Hajnalka
Molnar, Bela
Lakatos, Gabor
Sipos, Ferenc
Pregun, Istvan
Juhasz, Mark
Pronai, Laszlo
Schaff, Zsuzsa
Tulassay, Zsolt
Herszenyi, Laszlo
TI Increased p53 Expression in the Malignant Transformation of Barrett’s Esophagus is Accompanied by an Upward Shift of the Proliferative Compartment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Barrett’s esophagus; Reflux esophagitis; Dysplasia; Adenocarcinoma; Cell proliferation; p53 expression
ID Barrett’s esophagus; Reflux esophagitis; Dysplasia; Adenocarcinoma; Cell proliferation; p53 expression
AB Neoplastic progression in Barrett’s esophagus (BE) occurs by a multistep process associated with early molecular and morphological changes. This study evaluated cell proliferation and p53 expression and their correlation in the development and progression of esophageal adenocarcinoma. PCNA and p53 expressions were analyzed in biopsy samples by immunohistochemistry including patients with reflux esophagitis, BE, BE with concomitant esophagitis, Barrett’s dysplasia, esophageal adenocarcinoma and a control group without any histological changes. Progressive increase in cell proliferation and p53 expression was found in the sequence of malignant transformation of the esophageal mucosa. While cell proliferation was significantly lower in the control group compared with all other groups, there was no increase in p53 expression of esophageal tissues that were negative for dysplasia. Dysplastic BE tissues revealed significantly higher cell proliferation and p53 expression levels compared to BE, reflux esophagitis or BE with concomitant esophagitis. Both, cell proliferation and p53 expression were significantly higher in adenocarcinoma compared to BE or Barrett’s dysplasia. Interestingly, while just BE with concomitant esophagitis showed significantly higher p53 expression levels than BE, both, BE with concomitant esophagitis and reflux esophagitis revealed significantly higher cell proliferation levels compared to BE. Alterations of cell proliferation and p53 expression showed a strong correlation. Simultaneous activation of cell proliferation and p53 expression strongly suggest their association with esophageal epithelial tumor genesis and particularly, their specific role in the biology of esophageal adenocarcinoma. Quantification of these parameters in BE is thought to be useful to identify patients at higher risk for progression to adenocarcinoma.
C1 [Hritz, Istvan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Gyorffy, Hajnalka] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Lakatos, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Pregun, Istvan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Juhasz, Mark] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Pronai, Laszlo] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Herszenyi, Laszlo] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
RP Hritz, I (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM hritz.istvan@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 183
EP 192
DI 10.1007/s12253-008-9095-z
PG 10
ER
PT J
AU Szarvas, T
Jager, T
Droste, F
Becker, M
Kovalszky, I
Romics, I
Ergun, S
Rubben, H
AF Szarvas, Tibor
Jager, Tobias
Droste, Falk
Becker, Markus
Kovalszky, Ilona
Romics, Imre
Ergun, Suleyman
Rubben, Herbert
TI Serum Levels of Angiogenic Factors and their Prognostic Relevance in Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Serum; Angiopoietin; Tie2; VEGF; Prognosis
ID Bladder cancer; Serum; Angiopoietin; Tie2; VEGF; Prognosis
AB Angiogenesis plays a critical role in tumor growth. VEGF, angiopoietins (Ang-1, Ang-2) and their tyrosine kinase receptor Tie2 are major regulators of angiogenesis. The aim of this study was to evaluate the prognostic value of the serum levels of these factors in bladder cancer. We analyzed the serum samples of 117 bladder cancer patients and 64 healthy volunteers by enzyme linked immunosorbent assay (ELISA) for Ang-1, Ang-2, VEGF and the extracellular domain of Tie2. The statistical evaluation of the obtained data was performed via Kaplan–Meier log-rank test, univariate Cox analyses as well as Cox proportional hazards regression model. Serum Ang-1 levels of bladder cancer patients were significantly higher (p<0.001), while soluble Ang-2 and Tie2 levels were significantly lower (p=0.016 and p=0.001 respectively) in patients than those in controls. Cox univariate analysis revealed high sTie2 serum level as a risk factor for metastasis and as a borderline significant risk factor for disease related death (p=0.022 and p=0.081 respectively). These correlations were independent from tumor stage and grade in a Cox multivariate model (p=0.016 and p=0.069). These data indicate that the serum levels of analyzed angiogenic factors do change characteristically in bladder cancer. The soluble extracellular serum level of Tie2 may provide a stage and grade independent diagnostic tool to select a high risk group of bladder cancer patients.
C1 [Szarvas, Tibor] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Jager, Tobias] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Droste, Falk] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Becker, Markus] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
[Ergun, Suleyman] University Hospital of Essen, Institute of AnatomyEssen, Germany.
[Rubben, Herbert] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
RP Szarvas, T (reprint author), University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
EM sztibusz@gmail.com
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Tait CR, Jones PF, 2004, Angiopoietins in tumours: the angiogenic switch. J Pathol 204:1–10
Oka N, Yamamoto Y, Takahashi M, Nishitani M, Kanayama HO, Kagawa S, 2005, Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer. BJU Int 95:660– 663
Schliemann C, Bieker R, Thoennissen N, Gerss J, Liersch R, Kessler T, Buchner T, Berdel WE, Mesters RM, 2007, Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia. Leukemia 21:1901–1906
Park JH, Park KJ, Kim YS, Sheen SS, Lee KS, Lee HN, Oh YJ, Hwang SC, 2007, Serum angiopoietin-2 as a clinical marker for lung cancer. Chest 132:200–206
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Reusch P, Barleon B, Weindel K, Martiny-Baron G, Godde A, Siemeister G, Marme D, 2001, Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood. Angiogenesis 4:123–131
Harris AL, Reusch P, Barleon B, Hang C, Dobbs N, Marme D, 2001, Soluble Tie2 and Flt1 extracellular domains in serum of patients with renal cancer and response to antiangiogenic therapy. Clin Cancer Res 7:1992–1997
Findley CM, Cudmore MJ, Ahmed A, Kontos CD, 2007, VEGF induces Tie2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie2 signaling. Arterioscler Thromb Vasc Biol 27:2619–2626
Lin P, Polverini P, Dewhirst M, Shan S, Rao PS, Peters K, 1997, Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest 100:2072–2078
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 193
EP 201
DI 10.1007/s12253-008-9107-z
PG 9
ER
PT J
AU Toy, H
Yavas, O
Eren, OO
Genc, M
Yavas, C
AF Toy, Hatice
Yavas, Ozlem
Eren, Onder Orhan
Genc, Mine
Yavas, Cagdas
TI Correliation Between Osteopontin Protein Expression and Histological Grade of Astrocytomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteopontin; Brain tumor; Grade; Astrocytomas
ID Osteopontin; Brain tumor; Grade; Astrocytomas
AB Osteopontin is a ligand for the integrin proteins, which are cell surface receptors that mediate the physical and functional interactions between a cell and the extracellular matrix. The expression of osteopontin is reportedly increased in a number of transformed cell lines and tumor tissues. Furthermore, increased expression of osteopontin results in some infiltrative features of tumors. The aim of the study is to demonstrate that expression of osteopontin in human astrocytomas correlates with histological tumor grade. The expression of osteopontin in human astrocytomas was determined with immunohistochemistry. Median osteopontin expression levels were 1%, 7.5%, 60%, and 50% in grade I, II, III, and IV tumors, respectively. Osteopontin staining was significantly higher in high grade (grade III–IV) than low grade (grade I–II) tumors. These findings indicate that osteopontin immunoreactivity in human astrocytomas may correlate with the grade of a tumor.
C1 [Toy, Hatice] Selcuk University, Medicine Faculty, Department of Pathology, 42080 Konya, Meram, Turkey.
[Yavas, Ozlem] Selcuk University, Medical OncologyKonya, Turkey.
[Eren, Onder Orhan] Selcuk University, Medical OncologyKonya, Turkey.
[Genc, Mine] Selcuk University, Radiation OncologyKonya, Turkey.
[Yavas, Cagdas] Hacettepe University, Faculty of Medicine, Department of Radiation OncologyAnkara, Turkey.
RP Toy, H (reprint author), Selcuk University, Medicine Faculty, Department of Pathology, 42080 Konya, Turkey.
EM 11hatice@gmail.com
CR Denhardt DT, Noda M, 1998, Osteopontin expression and function: role in bone modelling. J Cell Biochem Supply, 30– 31):92–102
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Jang T, Savarese T, Low HP, Kim S, Vogel H, Lapointe D, Duong T, Litofsky NS, Weimann JM, Ross AH, Recht L, 2006, Osteopontin expression in intratumoral astrocytes marks tumor progression in gliomas induced by prenatal exposure to N-ethyl- N-nitrosourea. Am J Pathol 168(5):1676–85
Colin C, Baeza N, Bartoli C, Fina F, Eudes N, Nanni I, Martin PM, Ouafik L, Figarella-Branger D, 2005, Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization. Oncogene 12:1–9
Ding Q, Stewart J Jr, Prince CW, Chang PL, Trikha M, Han X, Grammer JR, Gladson CL, 2002, Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Cancer Res 62(18):5336–43
Said HM, Hagemann C, Staab A, Stojic J, Kuhnel S, Vince GH, Flentje M, Roosen K, Vordermark D, 2007, Expression patterns of the hypoxia-related genes osteopontin, CA9, erythropoietin, VEGF and HIF-1alpha in human glioma in vitro and in vivo. Radiother Oncol 83(3):398–405
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 203
EP 207
DI 10.1007/s12253-008-9130-0
PG 5
ER
PT J
AU Szendroi, M
Antal, I
Arato, G
AF Szendroi, Miklos
Antal, Imre
Arato, Gabriella
TI Adamantinoma of Long Bones: A Long-term Follow-up Study of 11 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adamantinoma; Long bones; Histology; Surgery
ID Adamantinoma; Long bones; Histology; Surgery
AB The aim of this study was to evaluate the clinicopathological features and prognostic significances of 11 histologically proven adamantinoma cases based on an average 12,7 year long follow-up. The male: female ratio was 8:3, aged between 4 and 80 years (mean 29,3 years). The initial diagnosis at referral was other than adamantinoma in six patients (fibrous dysplasia, carcinoma metastasis, osteofibrous dysplasia, bone cyst, nonossifying fibroma), referring to the differential diagnostic problems. All tumors were localized to the mid part of tibia. By histological evaluation, basaloid pattern on a background of fibrotic stroma dominated in six patients, while spindle and squamous features were less frequently seen. All adamantinomas were positive for cytokeratins often in coexpression with vimentin. No correlation was experienced between histology and clinical outcome. Intralesional curettage (2 pts) was followed by recurrence of the tumor. Wide resection was performed in eight patients with reconstruction using intercalary fibula autografts in seven patients. Reconstruction-related complications occurred in two third of the cases, all of them could however be controlled by repeated surgery. Six recurrences occurred in four patients, two of these recurrences occurred 20 and 16 years after initial surgery. One patient died 9 years after recognition of the tumor of pulmonary metastases. Adamantinoma of the long bones is a low grade malignant tumor, which clinical outcome is difficult to predict based on histology or surgical stage of the tumor. Wide surgical margin, e.g. resection the tumor reduces the rate of recurrence. This study underlines that recurrences do occur even decades after recognition the tumor, therefore a life-long follow-up of the patient is necessary.
C1 [Szendroi, Miklos] Semmelweis University, Department of Orthopedics, 27 Karolina Rd, 1113 Budapest, Hungary.
[Antal, Imre] Semmelweis University, Department of Orthopedics, 27 Karolina Rd, 1113 Budapest, Hungary.
[Arato, Gabriella] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Szendroi, M (reprint author), Semmelweis University, Department of Orthopedics, 1113 Budapest, Hungary.
EM szenmik@orto.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 209
EP 216
DI 10.1007/s12253-008-9125-x
PG 8
ER
PT J
AU Zhao, E
Xu, J
Yin, X
Sun, Y
Shi, J
Li, X
AF Zhao, Eryang
Xu, Jiankai
Yin, Xiaodong
Sun, Yu
Shi, Jinna
Li, Xia
TI Detection of Deregulated Pathways to Lymphatic Metastasis in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Deregulated pathway; Lymphatic metastasis; Oral squamous cell carcinomas
ID Deregulated pathway; Lymphatic metastasis; Oral squamous cell carcinomas
AB Oral squamous cell carcinoma (OSCC) is a common malignancy, in which lymph node metastasis is a major determinant of outcome. The pathway deregulation resulting from a large number of somatic genetic alterations in the development of the tumor, plays an important role in lymphatic metastasis process. To detect the deregulated pathways to lymphatic metastasis in OSCC, we performed pathway-oriented analysis using gene expression profile from 16 samples without lymphatic metastasis and 27 samples with lymphatic metastasis. We identified seven significantly (p<0.05) deregulated pathways: the erythropoietin (EPO) Signaling Pathway, Signaling Pathway from G-Protein Families, Cytokine–cytokine receptor interaction, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, Ribosome, Colorectal cancer, B cell receptor signaling pathway. The biological relevance of these pathways to OSCC is the focus of ongoing studies, as well as complex interactions and crosstalk between them. These pathways might provide additional clues about factors that regulate the course for OSCC patients and might offer new opportunities for therapeutic intervention.
C1 [Zhao, Eryang] Harbin Medical University, The Stomatological CollegeHarbin, China.
[Xu, Jiankai] Harbin Medical University, The Stomatological CollegeHarbin, China.
[Yin, Xiaodong] Harbin Medical University, The Stomatological CollegeHarbin, China.
[Sun, Yu] Harbin Medical University, The Stomatological CollegeHarbin, China.
[Shi, Jinna] Harbin Medical University, The Stomatological CollegeHarbin, China.
[Li, Xia] Harbin Medical University, The Stomatological CollegeHarbin, China.
RP Li, X (reprint author), Harbin Medical University, The Stomatological College, Harbin, China.
EM lixia@hrbmu.edu.cn
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Clohisy JC, Roy BC, Biondo C et al, 2003, Direct inhibition of NF-kappa B blocks bone erosion associated with inflammatory arthritis. J Immunol 171:5547–5553
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 217
EP 223
DI 10.1007/s12253-008-9102-4
PG 7
ER
PT J
AU Toth, J
Egervari, K
Klekner,
Bognar, L
Szanto, J
Nemes, Z
Szollosi, Z
AF Toth, Judit
Egervari, Kristof
Klekner, Almos
Bognar, Laszlo
Szanto, Janos
Nemes, Zoltan
Szollosi, Zoltan
TI Analysis of EGFR Gene Amplification, Protein Over-expression and Tyrosine Kinase Domain Mutation in Recurrent Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma multiforme; EGFR; Kinase inhibitor treatment
ID Glioblastoma multiforme; EGFR; Kinase inhibitor treatment
AB Gefitinib and erlotinib are both selective EGFR tyrosine kinase inhibitors (EGFR-TKIs) that have produced responses in a small subgroup of lung cancer patients. The strongest evidence for a role of EGFR in the biology of glioblastoma stems from clinical trials in which 15–20% of recurrent glioblastoma patients experienced significant tumour regression in response to these small-molecule EGFR kinase inhibitors. We examined the protein-kinase domain of the EGFR gene, EGFR protein expression and EGFR gene amplification in 20 cases of recurrent GBMs. EGFR protein over-expression was found in 65% of cases. EGFR protein over-expression was associated with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. No mutations were found in the TK domain of the EGFR gene. Our results confirm that mutations in the kinase domain are absent in recurrent GBM, and this might be a preponderant factor in the lack of major clinical responses of TKIs in GBM, recent studies have suggested that responsiveness to EGFR kinase inhibitors was strongly associated with coexpression of EGFRvIII and PTEN. Further prospective validation of EGFRvIII and PTEN as predictors of the clinical response to EGFR kinase inhibitors in recurrent GBM is strongly anticipated.
C1 [Toth, Judit] University of Debrecen, Department of Oncology, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Egervari, Kristof] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Klekner, Almos] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Bognar, Laszlo] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Szanto, Janos] University of Debrecen, Department of Oncology, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Nemes, Zoltan] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt.98, 4012 Debrecen, Hungary.
[Szollosi, Zoltan] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt.98, 4012 Debrecen, Hungary.
RP Szollosi, Z (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, 4012 Debrecen, Hungary.
EM szollosi@dote.hu
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Nicholson RI, Gee JM, Harper ME, 2001, EGFR and cancer prognosis. Eur J Cancer 37(suppl 4):S9–S15
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 225
EP 229
DI 10.1007/s12253-008-9082-4
PG 5
ER
PT J
AU Fregnani, RE
Sobral, ML
Alves, AF
Soares, AF
Kowalski, PL
Coletta, DR
AF Fregnani, Rodrigues Eduardo
Sobral, M Lays
Alves, Abreu Fabio
Soares, Augusto Fernando
Kowalski, Paulo Luis
Coletta, D Ricardo
TI Presence of Myofibroblasts and Expression of Matrix Metalloproteinase-2 (MMP-2) in Ameloblastomas Correlate with Rupture of the Osseous Cortical
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ameloblastoma; Matrix metalloproteinase-2; Myofibroblast; Prognosis; Urokinase plasminogen activator
ID Ameloblastoma; Matrix metalloproteinase-2; Myofibroblast; Prognosis; Urokinase plasminogen activator
AB Myofibroblasts are frequent in the stroma of neoplasm and by the expression of proteinases they can influence tumor infiltration and progression. In the present study, presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous solid multicystic ameloblastomas to determine their roles in the clinicopathological features of the tumors. Fifty seven ameloblastomas were analyzed immunohistochemically with antibodies against the isoform α of the smooth muscle actin (α-SMA), a specific marker of myofibroblasts, MMP-2 and uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic cell islands, of ~58% (n=33) of the ameloblastomas. MMP-2 and uPA were found in the cytoplasm of both neoplastic and stromal cells. A significant correlation between presence of myofibroblasts and MMP-2 expression was observed. Abundant presence of myofibroblast in the stroma of the tumors and expression of MMP-2 in the neoplastic or stromal cells were significantly correlated with rupture of the osseous cortical, which has been considered an important prognostic marker of ameloblastoma aggressiveness. Ours results suggest that abundant presence of myofibroblasts and expression of MMP-2 in solid ameloblastomas may be associated with a more aggressive infiltrative behavior.
C1 [Fregnani, Rodrigues Eduardo] A. C. Camargo Cancer Hospital, Department of Stomatology, R. Professor Antonio Prudente, 211 Sao Paulo-SP-Liberdade-CEP, 01509-010 Sao Paulo, Brazil.
[Sobral, M Lays] State University of Campinas, School of Dentistry, Department of Oral DiagnosisPiracicaba, Sao Paulo, Brazil.
[Alves, Abreu Fabio] A. C. Camargo Cancer Hospital, Department of Stomatology, R. Professor Antonio Prudente, 211 Sao Paulo-SP-Liberdade-CEP, 01509-010 Sao Paulo, Brazil.
[Soares, Augusto Fernando] A. C. Camargo Cancer Hospital, Department of PathologySao Paulo, Brazil.
[Kowalski, Paulo Luis] A. C. Camargo Cancer Hospital, Department of Head and Neck Surgery and OtorhinolaryngologySao Paulo, Brazil.
[Coletta, D Ricardo] State University of Campinas, School of Dentistry, Department of Oral DiagnosisPiracicaba, Sao Paulo, Brazil.
RP Fregnani, RE (reprint author), A. C. Camargo Cancer Hospital, Department of Stomatology, 01509-010 Sao Paulo, Brazil.
EM erfreg@terra.com.br;eduardofregnani@me.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 231
EP 240
DI 10.1007/s12253-008-9110-4
PG 10
ER
PT J
AU El-Sarha, IA
Magour, MG
Zaki, MS
El-Sammak, YM
AF El-Sarha, I Ashgan
Magour, M Gehan
Zaki, M Sameh
El-Sammak, Y Mohamed
TI Serum sFas and Tumor Tissue FasL Negatively Correlated with Survival in Egyptian Patients Suffering from Breast Ductal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sFas; FasL; Apoptosis; DNA ploidy; S-phase fraction
ID sFas; FasL; Apoptosis; DNA ploidy; S-phase fraction
AB Fas (CD95-APO-1), a member of tumor necrosis factor receptor super-family, exists in two forms, transmembrane and soluble (sFas). It had been suggested that circulating sFas levels and/or tissue FasL may reflect the severity of invasive breast ductal carcinoma. Few studies showed that neither DNA-index nor ploidy is an independent prognostic indicator, and there is no correlation with clinical outcome. The S-phase fraction (SPF) has been shown to be useful prognostic factor in both node-negative and node-positive tumors. The present work was done to find a correlation between sFas, tissue FasL, ploidy and SPF with prognostic factors and survival of breast ductal carcinoma patients. The present study included two groups; a patients group comprised 30 patients with breast ductal carcinoma and a control group that comprised 15 patients with benign breast swellings. Serum sFas was measured using commercially available ELISA kit and tissue FasL expression was studied using avidin–biotine immunohistochemical staining technique. Cell cycle studies were performed using flow cytometry. Serum sFas was significantly higher in breast ductal carcinoma group than in the benign breast swelling control group. A significant negative correlation between serum sFas and overall survival was found. Tissue FasL expression was directly correlated with distant metastasis and poor overall survival. A significant direct correlation was found between moderate and high SPF with worse pathologic parameters. Serum sFas level, tissue FasL immuno-expression and S-phase fraction are independent prognostic factors in breast ductal carcinoma cases.
C1 [El-Sarha, I Ashgan] Alexandria University, Medical Research Institute Teaching Hospital, Department of Chemical PathologyAlexandria, Egypt.
[Magour, M Gehan] Alexandria University, Medical Research Institute Teaching Hospital, Department of Chemical Pathology, 165 El Horreya StreetAlexandria, Egypt.
[Zaki, M Sameh] Alexandria University, Medical Research Institute, Department of Radiation SciencesAlexandria, Egypt.
[El-Sammak, Y Mohamed] Alexandria University, Medical Research Institute Teaching Hospital, Department of Chemical Pathology, 165 El Horreya StreetAlexandria, Egypt.
RP El-Sammak, YM (reprint author), Alexandria University, Medical Research Institute Teaching Hospital, Department of Chemical Pathology, Alexandria, Egypt.
EM myelsammak@doctors.org.uk
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 241
EP 250
DI 10.1007/s12253-008-9109-x
PG 10
ER
PT J
AU Kohut, E
Hajdu, M
Gergely, P
Gopcsa, L
Kilian, K
Paloczi, K
Kopper, L
Sebestyen, A
AF Kohut, Eszter
Hajdu, Melinda
Gergely, Peter
Gopcsa, Laszlo
Kilian, Katalin
Paloczi, Katalin
Kopper, Laszlo
Sebestyen, Anna
TI Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autoimmune; Signaling; Smad; SLE; TGFβ
ID Autoimmune; Signaling; Smad; SLE; TGFβ
AB Transforming growth factor β1 (TGFβ1) is an important immunosuppressive cytokine. Defects in its production by lymphocytes and the failure of TGFβ1 to regulate immunological functions have been described in SLE. Expression of TGFβ1 and the related signaling pathway was studied in the peripheral lymphocytes of SLE patients. The total plasma TGFβ1 level in active and inactive SLE patients compared to healthy controls was also measured. TGFβ1 and all downstream signaling elements were expressed in normal cells. However, in more than 50% of SLE patients the isolated Tcell population showed no TGFβ1mRNA expression and at least one member of the TGFβ1 pathway was also missing (TGFβ-RI, Smad2 and Smad3) in more than half of the patients. Total plasma TGFβ1 level was increased in both active and inactive SLE groups compared to normal controls (p< 0.05). These data raise questions about the availability of TGFβ1 signaling in lymphocytes in SLE patients, however, the elevated total plasma TGFβ1 level suggests that the failure of TGFβ1 effects is not the consequence of low level of this cytokine in SLE.
C1 [Kohut, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Hajdu, Melinda] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Gergely, Peter] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Gopcsa, Laszlo] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Kilian, Katalin] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Paloczi, Katalin] National Medical Center, Department of Hematology and Stem Cell TransplantationBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Sebestyen, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM anna@korb1.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 251
EP 256
DI 10.1007/s12253-008-9119-8
PG 6
ER
PT J
AU Bagheri, K
Alimoghadam, K
Pourfathollah, AA
Hassan, MZ
Hajati, J
Moazzeni, MS
AF Bagheri, Kambiz
Alimoghadam, Kamran
Pourfathollah, Akbar Ali
Hassan, Muhammad Zuhair
Hajati, Jamshid
Moazzeni, Mohammad Seyyed
TI The Efficient Generation of Immunocompetent Dendritic Cells from Leukemic Blasts in Acute Myeloid Leukemia: A Local Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dendritic cell; Differentiation; Immunotherapy; Iranian AML patients; Leukemia
ID Dendritic cell; Differentiation; Immunotherapy; Iranian AML patients; Leukemia
AB Dendritic cells (DCs) are the most important antigen presenting cells with potentially useful applications in cancer immunotherapy. Leukemic cells of patients with acute myeloid leukemia (AML) could be differentiated to DC-like cells possessing the ability of stimulating antileukemic immune response. Despite obvious progress in DC-based immunotherapy, some discrepancies were reported in differentiation potential of AML blasts from all patients toward DC like cells. The present study, as a local experience, was set up to generate DCs from AML blasts of various subtypes. Leukemic Blasts from 16 Iranian AML patients were differentiated into functional DCs by culturing in the presence of rhGM-CSF, rhIL-4 and TNFalpha for 8 days. The morphology, expression of key surface molecules and allostimulatory activity of resultant DCs were compared with primary blasts and cultured but cytokine untreated control groups. The pattern of angiotensin-converting enzyme (ACE) expression was used to approve the leukemic origin of generated DCs. Neoexpression or upregulation of DC-associated markers were occurred during culturing period in cytokine treated cells compared with primary blasts and cultured but cytokine untreated control groups: CD1a (63.22% vs. 3.22% and 11.79%), CD83 (41.27% vs. 0.11% and 0.70%), CD40 (15.17% vs. 0.00% and 0.04%), CD80 (49.96 vs. 0.02% and 0.32%), CD86 (56.49% vs. 0.50% and 5.71%) and HLA-DR (52.52% vs. 14.32% and 2.49%) respectively. The potency of generated DCs to induce allogeneic T cell proliferation increased significantly compared to pre and post culture control groups (27,533.4±2,548.3, 8,820.4±1,639.4 and 3,200.35±976 respectively). The expression pattern of ACE in AML-DCs, blast cells and DCs derived from normal monocytes (7.93%, 1.28% and 74.97% respectively) confirmed the leukemic origin of DCs. Our data confirmed the generation of sufficient AML-derived cells with the properties of DCs in all cases. This potency of AML blasts, offers a useful route for active immunotherapy of AML patients.
C1 [Bagheri, Kambiz] Tarbiat Modares University, Faculty of Medical Sciences, Department of ImmunologyTehran, Iran.
[Alimoghadam, Kamran] Tehran University of Medical Sciences, Research Center, Shariati Hospital, Hematology, Oncology and Bone Marrow TransplantationTehran, Iran.
[Pourfathollah, Akbar Ali] Tarbiat Modares University, Faculty of Medical Sciences, Department of ImmunologyTehran, Iran.
[Hassan, Muhammad Zuhair] Tarbiat Modares University, Faculty of Medical Sciences, Department of ImmunologyTehran, Iran.
[Hajati, Jamshid] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Moazzeni, Mohammad Seyyed] Tarbiat Modares University, Faculty of Medical Sciences, Department of ImmunologyTehran, Iran.
RP Moazzeni, MS (reprint author), Tarbiat Modares University, Faculty of Medical Sciences, Department of Immunology, Tehran, Iran.
EM Moazzeni@modares.ac.ir;smoazzeni@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 257
EP 267
DI 10.1007/s12253-008-9105-1
PG 11
ER
PT J
AU Kovacs,
Hadjiev, J
Lakosi, F
Antal, G
Vandulek, Cs
Somogyine Ezer,
Bogner, P
Horvath,
Repa, I
AF Kovacs, Arpad
Hadjiev, Janaki
Lakosi, Ferenc
Antal, Gergely
Vandulek, Csaba
Somogyine Ezer, Eva
Bogner, Peter
Horvath, Agnes
Repa, Imre
TI Dynamic MR Based Analysis of Tumor Movement in Upper and Mid Lobe Localized Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Dynamic MR; Tumor motion
ID Lung cancer; Dynamic MR; Tumor motion
AB Background and purpose: Tumor motion is a very important factor in the radiotherapy of lung cancer. Uncertainty resulting from tumor movement must be considered in 3D therapy planning especially in case of IMRT or stereotactic therapy. The aim of our dynamic MR based study was to detect tumor movements in upper and mid lobe lung tumors. Patient and methods: Twenty-four patients with newly diagnosed stage II-IV lung cancer were enrolled into the study. According to tumor localization in the right S1–S3 segments 9, in the right S4–S6 segments 2, in the left S1–S3 segments 9 and in the left S4–S6 segments 4 lesions were detected. In normal treatment position individual dynamic MR examinations were performed in axial, sagittal and coronal planes (100 slices/30 sec). For tumor motion analysis E-RAD PAC's software was used. Results: Movements of the tumor under normal breathing conditions were registered in the three main directions. The mean antero-posterior deviation was 0,109 cm (range: 0,063 cm–0,204 cm), the mean mediolateral deviation was 0,114 cm (range: 0,06 cm– 0,244 cm). The greatest deviation was measured in cranio–caudal direction (mean: 0,27 cm, range: 0,079 cm– 0,815 cm). The mean direction independent deviation was 0,18 cm (range: 0,09 cm– 0,48 cm). Conclusion: Dynamic MR is a sensitive and well tolerated method for tumor motion monitoring in high precision 3D therapy planning of lung cancer patients. Our results demonstrate that tumors located in the upper and mid lobes have moderate breath synchronous movements. The greatest deviation occur in cranio–caudal direction.
C1 [Kovacs, Arpad] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Hadjiev, Janaki] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Lakosi, Ferenc] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Antal, Gergely] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Vandulek, Csaba] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Somogyine Ezer, Eva] Kaposi Mor Teaching Hospital, Tallian Gy. u. 20–32, H-7400 Kaposvar, Hungary.
[Bogner, Peter] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
[Horvath, Agnes] University of Debrecen, Medical and Health Science Center, Institute of Nuclear Medicine, Nagyerdei krt 98, H-4012 Debrecen, Hungary.
[Repa, Imre] Kaposi Mor Teaching Hospital, Guba S. u 40, H-7400 Kaposvar, Hungary.
RP Horvath, (reprint author), University of Debrecen, Medical and Health Science Center, Institute of Nuclear Medicine, H-4012 Debrecen, Hungary.
EM horvakos@freemail.hu
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Lagerwaard FJ, van Sornsen de Koste JR, Lagerwaard FJ et al, 2001, Multiple “slow” CT scans for incorporating lung tumor mobility in radiotherapy planning. Int J Radiat Oncol Biol Phys 51:932–937
Seppenwoolde Y, Shirato H, Kitamura K et al, 2002, Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy. Int J Radiat Oncol Biol Phys 53:822–834
de Boer HC, van Sornsen de Koste JR, Senan S et al, 2001, Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning. Int J Radiat Oncol Biol Phy 49:857–868
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van Sornsen de Koste JR, Lagerwaard FJ, Nijssen-Visser MR et al, 2003, Tumor location cannot predict the mobility of lung tumors: A 3D analysis of data generated from multiple CT scans. Int J Radiat Oncol Biol Phys 56:348–354
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Mah D, Hanley J, Rosenzweig K, Yorke E, Braban L, Ling C, Leibel A, Mageras G, 2000, Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer. Int J Radiat Oncol Biol Phys 48:1175–1185
Plathow C, Hof H, Kuhn S, Puderbach M, Ley S, Biederer J, Claussen CD, Huber PE, Schaefer J, Tuengerthal S, Kauczor HU, 2006, Therapy monitoring using dynamic MRI: analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy. Eur Radiol 16(9):1942–1950 Sep, Epub 2006 Apr 21
Plathow C, Ley S, Fink C et al, 2004, Evaluation of chest motion and volumetry during the breathing cycle by dynamic MRI in healthy subjects: comparison with pulmonary function tests. Invest Radiol 39:202–209
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 269
EP 277
DI 10.1007/s12253-008-9101-5
PG 9
ER
PT J
AU Nagy, B
Szendroi, A
Romics, I
AF Nagy, Balint
Szendroi, Attila
Romics, Imre
TI Overexpression of CD24, c-myc and Phospholipase 2A in Prostate Cancer Tissue Samples Obtained by Needle Biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Gene expression; CD24; c-myc; Phospholipase 2A
ID Prostate cancer; Gene expression; CD24; c-myc; Phospholipase 2A
AB Altered CD24, c-myc and phospholipase 2a expression was reported in different cancers. Our aim was to measure the expression of these genes in prostate cancer tissues, and compare it to non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 20 prostate cancer (PCA) and 11 benign prostate hyperplasic (BPH) patients. RNA was isolated; cDNA synthetized, CD24, c-myc and phospholipase 2A (PL2A) expressions were determined by quantitative real-time PCR method. The expression of β-globin gene was measured for normalization of the gene expression results. Serum prostate specific antigen (PSA) levels were determined by microparticle enzyme immunoassay (MEIA) method. PSA levels were significantly different between the PCA and BPH groups, 252.37±308.33 ng/ml vs. 3.5±2.14 ng/ml (p=0.001), respectively. CD24 expression was 988.86±3041 ng/μl in prostate tumor and 4.00±4.25 ng/μl in the BPH group (p=0.035). The c-myc expression was 88.32±11.93 ng/μl in the prostate tumor and 17.08±21.75 ng/μl in the BPH group (p=0.02), and the PL2A 31.36±67.02 ng/μl was in PCA and 5.56±14.08 ng/μl in BPH (p=0.025). Gleason’s scores showed correlation with c-myc (p=0.019) and PSA (p=0.033) levels. Overexpression of PL2A, CD24 and c-myc was observed in prostate cancer samples using quantitative real-time PCR method.
C1 [Nagy, Balint] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Baross 27, 1088 Budapest, Hungary.
[Szendroi, Attila] Semmelweis University, Department of UrologyBudapest, Hungary.
[Romics, Imre] Semmelweis University, Department of UrologyBudapest, Hungary.
RP Nagy, B (reprint author), Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, 1088 Budapest, Hungary.
EM nabal@noi1.sote.hu
CR Muller H, Brenner H, 2006, Urine markers as possible tools for prostate cancer screening: review of performance characteristics and practicality. Clin Chem 52:562–573
Kopper L, Timar J, 2005, Genomics of prostate cancer: is there anything to “translate”. Pathol Oncol Res 11:197–203
Maitland NJ, Collins A, 2005, A tumour stem cell hypothesis for the origins of prostate cancer. BJU Int 96:1219–1223
Hughes C, Murphy A, Martin C et al, 2005, Molecular pathology of prostate cancer. J Clin Pathol 58:673–684
Quinn DI, Henshall SM, Sutherland LR, 2005, Molecular markers of prostate cancer outcome. Eur J Cancer 41:858–887
Glinsky VG, Glinskii BA, Stephenson JA et al, 2004, Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest 113:913–923
Prowatke I, Devens F, Benner A et al, 2006, Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays. Br J Cancer 96:82–88
Nupponen NN, Kakkola L, Koivisto P et al, 1998, Genetic alterations in hormone refractory recurrent prostate carcinomas. Am J Pathol 153:141–148
Kristiansen G, Denkert C, Schluns K et al, 2002, CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patients survival. Am J Pathol 161:1215–1221
Kristiansen G, Schluns K, Yongwei Y et al, 2003, CD24 is an independent prognostic marker of survival in non-small cell lung cancer patients. Br J Cancer 88:231–236
Kristiansen G, Winzer KJ, Mayordomo E et al, 2003, CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9:4906–4913
Kristiansen G, Pilarsky C, Pervan J et al, 2004, CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer. Prostate 58:183–192
Ponzielli R, Katz S, Barsyte-Lovejoy D et al, 2005, Cancer therapeutics: targeting the dark side of Myc. Eur J Cancer 41:2485–2501
Devi RG, Oldenkamp RJ, London AC et al, 2002, Inhibition of human chorionic gonadotropin β-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells. Prostate 53:200–210
Hirabayashi T, Shimuzu T, 2000, Localization and regulation of cytosolic phospholipase A2. Biochim Biophys Acta 1488:124–138
Dong Q, Patel M, Scott KF et al, 2006, Oncogenic action of phospholipase A2 in prostate cancer. Cancer Letters 240:9–16
Wikmam H, Seppanen JK, Sarhadi VK et al, 2004, Caveolins as tumor markers in lung cancer detected by combined use of cDNA and tissue microarrays. J Pathol 203:584–593
Kettunen E, Nicholson AG, Nagy B et al, 2005, L1CAM, INP10, P-cadherin, tPA and ITGB4 overexpression in malignant pleural mesothelioma primary tumors revealed by combined use of cDNA and tissue microarray. Carcinogenesis 26:17–25
Schostak M, Krause H, Miller K et al, 2006, Quantitative realtime RT-PCR of CD24 mRNA in the detection of prostate cancer. BMC Urol 119:1396–1402
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Ohl F, Jung M, Xu C et al, 2005, Gene expression studies in prostate cancer tissue: with reference gene should be selected for normalization? J Mol Med 83:1014–1024
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Bernard D, Pourtuer-Manzanedo A, Gil J et al, 2003, Myc confers androgen-independent prostate cancer cell growth. J Clin Invest 112:1724–1731
Shachaf CM, Kopelman AM, Arvanitis C et al, 2004, MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431:1112–1117
Arnold I, Watt FM, 2001, c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol 11:558–568
Liu YA, Roudier PM, True DL, 2004, Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. Am J Pathol 165:1543–1556
Hughes-Fulford M, Tjandrawinata RR, Li C-F et al, 2005, Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells. Carcinogenesis 26:1520–1526
Kallajoki M, Alanen KA, Nevalainen M et al, 1998, Group II phospholipase A2 in human male reproductive organs and genital tumors. Prostate 35:263–272
Shimuzu M, Matsumoto Y, Kurosawa T et al, 2008, Release of arachidonic acid induced by tumor necrosis factor-α in the presence of caspase inhibition: evidence for cytosolic phospholipase A2α- independent pathway. Biochem Pharmacol, DOI 10.1016/j. bcp.2007.11.020
Cummings BS, 2007, Phospholipase A2 as targets for anticancer drugs. Biochem Pharmacol 74:949–959
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 279
EP 283
DI 10.1007/s12253-008-9077-1
PG 5
ER
PT J
AU Kojima, M
Nakamura, N
Shimizu, K
Segawa, A
Kaba, S
Masawa, N
AF Kojima, Masaru
Nakamura, Naoya
Shimizu, Kazuhiko
Segawa, Atsuki
Kaba, Sadayuki
Masawa, Nobuhide
TI MALT Type Lymphoma Demonstrating Prominent Plasma Cell Differentiation Resembling Fibrous Variant of Hashimoto’s Thyroiditis: a Three Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MALT type lymphoma; Thyroid gland; Fibrous variant; Hashimoto’s thyroiditis; Immunohistochemistry
ID MALT type lymphoma; Thyroid gland; Fibrous variant; Hashimoto’s thyroiditis; Immunohistochemistry
AB Fibrous variant of Hashimoto’s thyroiditis (HT) is characterized by marked fibrous replacement of one third or more of the thyroid parenchyma. We present here three cases of mucosa associated lymphoid tissue (MALT) type lymphoma demonstrating prominent plasma cell differentiation resembling fibrous variant of HT. Histologically, thyroid structures were disturbed by a diffuse and focally nodular infiltration by mature plasma cells and cells with plasma cell differentiation against a background of prominent hyalinosis. In addition, scattered centrocyte-like (CCL) cells and lymphoepithelial lesions were observed in all three lesions. A portion of the resected specimens in all three cases exhibited HT. However, immunohistochemical study demonstrated that the plasma cells and CCL-cells of these three lesions had monotypic intracytoplasmic kappa light chain. Moreover, these three lesions demonstrated a clonal band on polymerase chain reaction assay for the immunoglobulin heavy chain gene. To avoid underdiagnosis, we emphasize that careful attention should be paid to these immunological features as well as to morphological findings.
C1 [Kojima, Masaru] Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 617–1, Takabayashinishi-cho, 373-8550 Ohta, Japan.
[Nakamura, Naoya] Tokai University School of Medicine, Department of PathologyIsehara, Japan.
[Shimizu, Kazuhiko] Ashikaga Red Cross Hospital, Department of Pathology and Clinical LaboratoriesAshikaga, Japan.
[Segawa, Atsuki] Dokkyo Medical University School of Medicine, Department of Diagnostic and Anatomic PathologyMibu, Japan.
[Kaba, Sadayuki] Gunma University, Faculty of Medicine, Department of Laboratory ScienceMaebashi, Japan.
[Masawa, Nobuhide] Dokkyo Medical University School of Medicine, Department of Diagnostic and Anatomic PathologyMibu, Japan.
RP Kojima, M (reprint author), Gunma Cancer Center Hospital, Department of Pathology and Clinical Laboratories, 373-8550 Ohta, Japan.
EM mkojima@gunma-cc.jp
CR Hyjek E, Isaacson PG, 1988, Primary B cell lymphoma of the thyroid and its relationship to Hashimoto’s thyroiditis. Hum Pathol 19:1315–1326
Isaacson PG, Norton AJ, 1994, Extranodal lymphomas. Churchill Livingstone, Edinburgh
Katz SM, Vickery AL Jr, 1974, The fibrous variant of Hashimoto’s thyroiditis. Hum Pathol 2:161–170
Harach HR, Williams ED, 1983, Fibrous thyroiditis. An immunopathological study. Histopathology 7:739–751
Derringer GA, Thompson LDR, Frommelt RA et al, 2000, Malignant lymphoma of the thyroid gland. A clinicopathologic study of 108 cases. Am J Surg Pathol 24:623–639
Wan JH, Trainor KJ, Brisco MJ et al, 1990, Monoclonality in B cell lymphoma detected in paraffin wax embedded sections using the polymerase chain reaction. J Clin Pathol 43:888–890
Lennert K, Feller AC, 1992, Histopathology of non-Hodgkin’s lymphomas, Based on the updated Kiel classification). Springer, Berlin
Hussong JW, Perkins SL, Schnitzer B et al, 1999, Extramedullary plasmacytoma. A form of marginal zone cell lymphoma. Am J Clin Pathol 111:111–115
Kovacs CS, Mant MJ, Nguyen GK et al, 1994, Plasma cell lesions of the thyroid: report of a case of solitary plasmacytoma and a review of the literature. Thyroid 4:65–71
Coffin CM, Watterson J, Priest JC et al, 1995, Extrapulmonary inflammatory myofibroblastic tumor, inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 19:859–872
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Kriegel L, Guetgemann I, Zhou H, 2007, Plasma cell granuloma of the thyroid gland mimicking carcinoma: A case report and review of the literature. Pathol Res Pract 203:813–817
Deniz K, Patrioglu, Oketen T, 2008, Plasma cell granuloma of the thyroid. Case report. APMIS 117:167–172
Kremer M, Ott G, Nathrath M et al, 2005, Primary extramedullary plasmacytoma and multiple myeloma: Phenotypic differences revealed by immunohistochemical analysis. J Pathol 205: 92–101
Feller AC, Diebold J, 2003, Histopathology of nodal and extranodal non-Hodgkin's lymphomas. Springer, Berlin
Yatabe Y, Suzuki R, Matsuno Y et al, 2001, Morphological spectrum of cyclin D-1 positive mantle cell lymphoma: study of 168 cases. Pathology International 51:747–761
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 285
EP 289
DI 10.1007/s12253-008-9108-y
PG 5
ER
PT J
AU Saw, S
Thomas, N
Gleeson, JM
Bodi, I
Connor, S
Hortobagyi, T
AF Saw, Sonia
Thomas, Nick
Gleeson, J Michael
Bodi, Istvan
Connor, Steve
Hortobagyi, Tibor
TI Giant Cell Tumour and Central Giant Cell Reparative Granuloma of the Skull: do These Represent Ends of a Spectrum? A Case Report and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Giant cell tumour; Giant cell reparative granuloma; Histology; Skull bone
ID Giant cell tumour; Giant cell reparative granuloma; Histology; Skull bone
AB Giant cell tumour (GCT) of bone is an uncommon primary bone neoplasm typically occurring at the epiphyses of long bones in young adults. They are osteolytic neoplasms with approximate local recurrence rates of 25%, and 2% of patients develop pulmonary metastases. These tumours appear very rarely in the skull, with those few reported cases arising predominantly in the sphenoid and occasionally the temporal bones. They demonstrate benign histological features, but are locally aggressive and surgical excision is the treatment of choice. It is widely believed that giant cell tumours should be distinguished from other giant cell lesions, importantly central giant cell reparative granulomata (CGCG) which are thought to have a lower recurrence rate and for which no cases of malignant transformation or metastases have been reported. Investigators have noted that giant cell lesions in the skull bones may be unique and that GCT and CGCG may be part of a spectrum of a single disease process. We present a case of a giant cell tumour of the temporal bone which illustrates and re-emphasises this concept and review the literature on these lesions.
C1 [Saw, Sonia] King’s College Hospital, Clinical Neuropathology, De Crespigny Park, SE5 8AF London, UK.
[Thomas, Nick] King’s College Hospital, Department of NeurosurgeryLondon, UK.
[Gleeson, J Michael] Guy’s Hospital, Department of Otolaryngology and Skull Base SurgeryLondon, UK.
[Bodi, Istvan] King’s College Hospital, Clinical Neuropathology, De Crespigny Park, SE5 8AF London, UK.
[Connor, Steve] King’s College Hospital, Department of NeuroradiologyLondon, UK.
[Hortobagyi, Tibor] King’s College Hospital, Clinical Neuropathology, De Crespigny Park, SE5 8AF London, UK.
RP Hortobagyi, T (reprint author), King’s College Hospital, Clinical Neuropathology, SE5 8AF London, UK.
EM tibor.hortobagyi@iop.kcl.ac.uk
CR Reid R, Banerjee S, Sciot R, 2002, Giant cell tumour. In: Fletcher C, Unni K, Mertens F, eds, Pathology and genetics of tumours of soft tissue and bone, WHO classification of tumours. IARC, Lyon, pp 310–312
Bertoni F, Unni K, Beabout J et al, 1992, Giant cell tumour of the skull. Cancer 70(5):1124–1132
Hirschl S, Katz A, 1974, Giant cell reparative granuloma outside the jaw bone. Hum Pathol 5(2):171–181
Williams J, Thorell W, Treves J et al, 2000, Giant cell reparative granuloma of the petrous temporal bone: a case report and literature review. Skull Base Surg 10(2):89–93
Ung F, Li K, Keith D et al, 1998, Giant cell reparative granuloma of the temporal bone: Case report and review of the literature. Otolaryngol Head Neck Surg 118:525–529
Auclair P, Cuenin P, Kratochvil F et al, 1988, A clinical and histomorphologic comparison of the central giant cell granuloma and the giant cell tumour. Oral Surg 66:197–208
Whitaker S, Waldron C, 1993, Central giant cell lesions of the jaws. a clinical, radiologic and histopathologic study. Oral Surg Oral Med Oral Pathol 75(2):199–208
Jaffe H, 1953, Giant-cell reparative granuloma, traumatic bone cyst, and fibrous, fibro-osseous, dysplasia of the jawbones. Oral Surg 6:159–175
Kashiwagi N, Hirabuki N, Andou K et al, 2006, MRI and CT findings of the giant cell tumours of the skull; five cases and a review of the literature. Eur J Radiol 58:435–443
Elder J, Berry C, Gonzalez-Gomez I et al, 2007, Giant cell tumour of the skull in paediatric patients. J Neurosurg 107(Supp 1 Paed):69–74
Lee M-Y, Lee E-J, 2006, Giant cell tumour of the petrous temporal bone with direct invasion into the middle ear. J Craniofac Surg 17:797–800
Wulling M, Engels C, Jesse N et al, 2001, The nature of giant cell tumour of bone. J Cancer Res Clin Onc 127(8):467–474
Nemoto Y, Inoue Y, Tashiro T et al, 1995, Central giant cell granuloma of the temporal bone. Am J Neuroradiol 16:982– 985
Dickson B, Li S-Q, Wunder J et al, 2008, Giant cell tumour of bone express p63. Mod Pathol 21:369–375
Leonard J, Gokden M, Kyriakos M et al, 2001, Malignant giantcell tumour of the parietal bone: case report and review of the literature. Neurosurgery 48(2):424–429
Schwartz H, Eskew J, Butler M, 2002, Clonality studies in giant cell tumour of bone. J Orthop Res 20(2):387–390
Antal I, Sapi Z, Szendroi M, 1999, The prognostic significance of DNA cytophotometry and proliferation index, Ki-67, in giant cell tumours of bone. Int Orthop 23(6):315–319
Antal I, Sapi Z, Szendroi M, 2000, Malignant transformation of giant cell tumour in the distal radius. Value of the DNA cytophotometry Orthopade 29(7):677–683. German
Rousseau M, Handra-Luca A, Lazennec J et al, 2004, Metachronous multicentric giant-cell tumour of the bone in the lower limb. case report and Ki-67 immunohistochemistry study. Virchows Arch 445(1):79–82
Fukunaga M, Nikaido T, Shimoda T et al, 1992, A flow cytometric analysis of giant cell tumours of bone including two cases with malignant transformation. Cancer 70(7):1886– 1894
Sara A, Ayala A, el-Naggar A et al, 1990, Giant cell tumour of bone. a clinicopathologic and DNA flow cytometric analysis. Cancer 66(10):2186–2190
Sulh MA, Greco MA, Jiang T et al, 1996, Proliferation index and vascular density of giant cell tumours of bone: are they prognostic markers? Cancer 77(10):2044–2051
Dahlin D, Unni K, 1986, Bone Tumours—General aspects and data on 8542 cases, 4th edn. Thomas, Springfield
Bertoni F, Bacchini P, Staals E, 2003, Malignancy in giant cell tumour of bone. Cancer 97(10):2520–2529
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 291
EP 295
DI 10.1007/s12253-008-9124-y
PG 5
ER
PT J
AU Koseoglu, DR
Ozkan, N
Filiz, ON
Kayaoglu, HA
Aydin, M
Culha, NE
Ersoy, FO
AF Koseoglu, Dogan Resit
Ozkan, Namik
Filiz, Onuk Nurper
Kayaoglu, Huseyin Ayhan
Aydin, Mehtap
Culha, N Emre
Ersoy, F Omer
TI Intranodal Palisaded Myofibroblastoma; a Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myofibroblastoma; Intranodal palisaded myofibroblastoma; Amianthoid fiber
ID Myofibroblastoma; Intranodal palisaded myofibroblastoma; Amianthoid fiber
AB Intranodal palisaded myofibroblastoma (IPM) also called as intranodal hemorrhagic spindle cell tumor with amianthoid fibers is a distinctive and rare mesenchymal neoplasm of lymph nodes. This entity generally misdiagnosed as intranodal Kaposi’s sarcoma or schwannoma in past. In contrast to Kaposi’s sarcoma, it behaves in a benign fashion and does not need any further therapy except total surgical resection of the mass. This neoplasm has a great predilection for the inguinal region. The lesion presents typically as a unilateral, painless, solitary mass. To our knowledge, approximately 53 cases of IPM have been reported in the English-language literature. We present a 43-year-old-male patient with IPM and discuss histological, immunohistochemical features and pathogenesis of this rare benign neoplasm.
C1 [Koseoglu, Dogan Resit] Gaziosmanpasa University, School of Medicine, Department of Pathology, 60030 Tokat, Turkey.
[Ozkan, Namik] Gaziosmanpasa University, School of Medicine, Department of General SurgeryTokat, Turkey.
[Filiz, Onuk Nurper] Gaziosmanpasa University, School of Medicine, Department of Pathology, 60030 Tokat, Turkey.
[Kayaoglu, Huseyin Ayhan] Gaziosmanpasa University, School of Medicine, Department of General SurgeryTokat, Turkey.
[Aydin, Mehtap] Ankara Ataturk Training and Research Hospital, 1st Pathology ClinicAnkara, Turkey.
[Culha, N Emre] State Hospital of Sincan, Laboratory of PathologyAnkara, Turkey.
[Ersoy, F Omer] Gaziosmanpasa University, School of Medicine, Department of General SurgeryTokat, Turkey.
RP Koseoglu, DR (reprint author), Gaziosmanpasa University, School of Medicine, Department of Pathology, 60030 Tokat, Turkey.
EM residdogan@hotmail.com
CR Weiss SW, Gnepp DR, Bratthauer GL, 1989, Palisaded myofibribroblastoma. A benign mesenchymal tumor of lymph node. Am J Surg Pathol 13:341–346
Suster S, Rosai J, 1989, Intranodal hemorrhagic spindle-cell tumor with “amianthoid” fibers. Report of six cases of a distinctive mesenchymal neoplasm neoplasm of the inguinal region that simulates Kaposi’s sarcoma. Am J Surg Pathol 13:347–357
Lee JY-Y, Abell E, Shevichik GJ, 1989, Solitary spindle cell tumor with myoid differentiation of the lymph node. Arch Pathol Lab Med 113:547–550
Alguacil-Garcia A, 1992, Intranodal myofibroblastoma in a submandibular lymph node. Am J Clin Pathol 97:69–72
Fletcher CDM, Stirling RW, 1990, Intranodal myofibroblastoma presenting in the submandibular region: evidence of a broader clinical and histologic spectrum. Histopathology 16:287–294
Michal M, Chlumska A, Povysilova V, 1992, Intranodal “amianthoid” myofibroblastoma: report of six cases:immunohistochemical and electron microscopical study. Pathol Res Pract 188:199–204
Creager AJ, Garwacki CP, 1999, Recurrent intranodal palisaded myofibroblastoma with metaplastic bone formation. Arch Pathol Lab Med 123:433–436
Bigotti G, Coli A, Mottolese M, di Filippo F, 1991, Selective location of palisaded myofibroblastoma with amianthoid fibres. J Clin Pathol 44:761–764
Skalova A, Michal M, Chlumska A, LeivoI, 1992, Collagen composition and ultrastructure of the so-called amianthoid fibres in palisaded myofibroblastoma. Ultrastructural and immunohistochemical study. J Pathol 167:335–340
Kleist B, Poetsch M, Schmoll J, 2003, Intranodal palisaded myofibroblastoma with overexpression of cyclin D1. Arch Pathol Lab Med 127:1040–1043
Lioe TF, Allen DC, Bell JC, 1994, A case of multicentric intranodal palisaded myofibroblastoma. Histopathology 24:173–175
Barbareschi M, Mariscotti C, Ferrero S, Pignatiello U, 1990, Intranodal haemorrhagic spindle cell tumor: a benign Kaposi like nodal tumor. Histopathology 17:93–96
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Eyden BP, Harris M, Greywoode GIN, Christensen L, Banerjee SS, 1996, Intranodal myofibroblastoma: report of a case. Ultrastruct Pathol 20:79–88
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Ciralik H, Ezberci F, Bulbuloglu E, Aydin A, 2005, Intranodal palisaded myofibroblastoma and differential diagnosis: a case report. Chin Med J 118(20):1758–1760
Perez-Mies B, Campos AI, 2008, Intranodal palisaded myofibroblastoma. Arch Pathol Lab Med 132(8):1224–1225
Cobanoglu U, Siviloglu C, Ersoz S, Ozoran Y, 2006, Intranodal palisaded myofibroblastoma with metaplastic bone formation. Saudi Med J 27(8):1249–1250
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 297
EP 300
DI 10.1007/s12253-008-9122-0
PG 4
ER
PT J
AU Yano, H
Ohe, N
Shinoda, J
Yoshimura, Shi
Iwama, T
AF Yano, Hirohito
Ohe, Naoyuki
Shinoda, Jun
Yoshimura, Shin-ichi
Iwama, Toru
TI Immunohistochemical Study Concerning the Origin of Neurocytoma—A Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Extraventricle; Musashi 1; Neural stem cell; Neurocytoma; Origin; Subependymal
ID Extraventricle; Musashi 1; Neural stem cell; Neurocytoma; Origin; Subependymal
AB A 26-year-old woman presented with rapid tumor growth in her left frontal lobe during 9 years of observation. Operative findings revealed a massive tumor connected to gelatinous, transparent membranous tissue (MT), which extended from the paraventricular zone and continued into the lateral ventricle. Histological diagnosis was atypical neurocytoma. Immunohistochemical analyses revealed that the tumor was strongly positive for not only neural markers but also a glial marker, while the MT was positive for a neural marker. The Ki-67/MIB-1 labeling index was 9.1% in the tumor body and 0% in the MT. Musashi 1, a marker of neural stem cells, was strongly positive in both the tumor body and the MT. We speculate that the tumor growth was due to a rapid decline of the Musashi 1-positive cells to glial differentiation. These cells may be candidates for the origin of the tumor.
C1 [Yano, Hirohito] Gifu University Graduate School of Medicine, Department of Neurosurgery, 1-1 Yanagido, 501-1194 Gifu, Japan.
[Ohe, Naoyuki] Gifu University Graduate School of Medicine, Department of Neurosurgery, 1-1 Yanagido, 501-1194 Gifu, Japan.
[Shinoda, Jun] Kizawa Memorial Hospital, Department of Neurosurgery, Chubu Medical Center for Prolonged Traumatic Brain DysfunctionMinokamo, Japan.
[Yoshimura, Shin-ichi] Gifu University Graduate School of Medicine, Department of Neurosurgery, 1-1 Yanagido, 501-1194 Gifu, Japan.
[Iwama, Toru] Gifu University Graduate School of Medicine, Department of Neurosurgery, 1-1 Yanagido, 501-1194 Gifu, Japan.
RP Yano, H (reprint author), Gifu University Graduate School of Medicine, Department of Neurosurgery, 501-1194 Gifu, Japan.
EM hirohito@gifu-u.ac.jp
CR Elek G, Slowik F, Eross L, Toth S et al, 1999, Central neurocytoma with malignant course. Neuronal and glial differentiation and craniospinal dissemination. Pathol Oncol Res 5:155– 159
Kim BJ, Kim SS, Kim YI et al, 2004, Forskolin promotes astroglial differentiation of human central neurocytoma cells. Exp Mol Med 29:52–56
Kubota T, Hayashi M, Kawano H et al, 1991, Central neurocytoma: immunohistochemical and ultrastructural study. Acta Neuropathol, Berl, 81:418–427
Valduesza JM, Westphal M, Vortmeyer A et al, 1996, Central neurocytoma: clinical, immunohistologic, and biologic findings of a human neuroglial progenitor tumor. Surg Neurol 45:49–56
von Deimling A, Janzer R, Kleihues P et al, 1990, Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies. Acta Neuropathol, Berl, 79:473–479
von Deimling A, Kleihues P, Saremaslani P et al, 1991, Histogenesis and differentiation potential of central neurocytomas. Lab Invest 64:585–591
Westphal M, Stavrou D, Nausch H et al, 1994, Human neurocytoma cells in culture show characteristics of astroglial differentiation. J Neurosci Res 38:698–704
You H, Kim YI, Im SY et al, 2005, Immunohistochemical study of central neurocytoma, subependymoma, and subependymal giant cell astrocytoma. J Neurooncol 74:1–8
Kanemura Y, Mori K, Sakakibara S et al, 2001, Musashi 1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity. Differentiation 68:141–152
Toda M, Iizuka Y, Yu W et al, 2001, Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia 34:1–7
Uchida K, Mukai M, Okano H et al, 2004, Possible oncogenicity of subventricular zone neural stem cells: case report. Neurosurgery 55:977–978
Lee MK, Rebhun LI, Frankfurter A, 1990, Posttranslational modification of class III β-tubulin. Proc Natl Acad Sci USA 87:7195–7199
Menezes JR, Luskin MB, 1994, Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon. J Neurosci 14:5399–5416
Mullen RJ, Buck CR, Smith AM, 1992, NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201–211
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2009
VL 15
IS 2
BP 301
EP 305
DI 10.1007/s12253-008-9106-0
PG 5
ER
PT J
AU Keszthelyi, A
Majoros, A
Nyirady, P
Mayer, P
Bach, D
Romics, I
AF Keszthelyi, Attila
Majoros, Attila
Nyirady, Peter
Mayer, Peter
Bach, Dietmar
Romics, Imre
TI Voiding Symptoms and Urodynamic Findings in Patients with Modified Ileal Neobladde
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Radical cystectomy; Reddy neobladder; Urinary incontinence; Urodynamics
ID Bladder cancer; Radical cystectomy; Reddy neobladder; Urinary incontinence; Urodynamics
AB The aim of our study was to find the cause of urinary incontinence and voiding dysfunction in patients undergoing radical cystectomy and orthotopic bladder replacement with modified ileal neobladder (Reddy). Twenty-eight incontinent patients (operated on between 1988 and 2004) were involved in our examination. Based on the complaints of the patients, continence status was evaluated and divided into two groups: group I: partially incontinent (only night-time incontinence) n=11 (39.3%) and group II: totally incontinent (night-time and daytime incontinence) n=17 (60.7%). Detailed urodynamic examination (enterocystometry and urethral pressure profile) in addition to involuntary neobladder contractions and capacity detection were carried out on all patients. Furthermore resting pressure and maximal voluntary contraction ability of the sphincter were determined and statistically analyzed in both groups. Significant difference was noticed in resting pressure and maximal voluntary contraction ability of the sphincter among the partially incontinent and totally incontinent patients. Frequency, intensity and duration of involuntary neobladder contractions also showed significant differences between the two groups. Incontinence of neobladder depends not only on the destruction of resting and contraction capability of the urethral sphincter, but also on the presence or absence of involuntary contractions in the wall of the neobladder and decreased capacity of the neobladder.
C1 [Keszthelyi, Attila] Semmelweis UniversityBudapest, Hungary.
[Majoros, Attila] Semmelweis UniversityBudapest, Hungary.
[Nyirady, Peter] Semmelweis UniversityBudapest, Hungary.
[Mayer, Peter] Semmelweis UniversityBudapest, Hungary.
[Bach, Dietmar] Semmelweis UniversityBudapest, Hungary.
[Romics, Imre] Semmelweis UniversityBudapest, Hungary.
RP Keszthelyi, A (reprint author), Semmelweis University, Budapest, Hungary.
EM attilakeszthelyi@hotmail.com
CR Couvelaire R, 1952, Le reservoir ileal de substitution apres la cystectomia total chez l’homme. J d’Urol 57:408–411
Lilien OM, Camey M, 1984, 25-year experience with replacement of the human bladder, Camey procedure). J Urol 132: 886–889
Hautmann RE, Egghart G, Frohnenberg D, Miller K, 1988, The ileal neobladder. J Urol 136:27–31
Reddy PK, Lange PH, Fraley EE, 1991, Total bladder replacement using detubularised sigmoid colon: technique and results. J Urol 145:51–55
Studer UE, Ackermann D, Casanova GA, Zingg EJ, 1989, Three years experience with ileal low pressure bladder substitute. BJ Urol 63:43–46
Reddy PK, 1987, Non stomal continent reservoir: use of detubularized ileal segment for bladder replacement. World J Urol 5:190–193
Arai Y, Taki Y, Kawase N, Terachi T, Kakehi Y, Okada T, 1999, Orthotopic ileal neobladder in male patients: functional outcames of 66 cases. Int J Urol 6:388–392
Hobisch A, Kadir T, Kinzl J, 2001, Life after cystectomy and orthotopic neobladder versus ileal conduit urinary diversion. Seminars Urol Oncol 19:18–23
Kulkarni JN, Pramesh CS, Rathi S, Pantvaidya GH, 2002, Longterm results of orthotopic neobladder reconstruction after radicals cystectomy. BJ Urol 91:485–488
Skolarikos A, Deliveliotis C, Alargof E, Ferakis N, Protogerou V, Dimopoulos C, 2004, Modified ileal neobladder for continent urinary diversion: functional results after 9 years of experience. Urol 171:2298–2301
Laguna MP, Brenninkmeier M, Bellon JA, Marrero R, Wijkstra H, Rosette J, Isorna S, 2005, Long term functional and urodynamic results of 50 patients receiving a modified sigmoid neobladder created with a short distal segment. J Urol 174:963–967
Yadav SS, Sadadukhi C, Sharma KK, Yadav RG, Mathur R, 2006, Sigmoid orthotopic neobladder after radical cystectomy for bladder tumour: an Indian experience. BJU Inter 99:403–406
Jensen JB, Lundbeck F, Jensen KME, 2006, Comlications and neobladder function of the Hautmann orthotopic ileal neobladder. BJU Inter 98:1289–1294
Giannantoni A, Mearini E, Di Stasi SM, Mearini L, Bini V, Pizzirusso G, 2004, Assesment of bladder and urethral spichteric function before and after radical retropubic prostatectomy. J Urol 171:1563–1566
Hammerer P, Huland H, 1997, Urodynamic evaluation of changes in urinary control after radical retropubic prostatectomy. J Urol 157:233–236
Majoros A, Bach D, Keszthelyi A, Hamvas A, Romics I, 2006, Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy, prospective urodynamic study). Neuroul Urodyn 25:2–7
Gerharz E, Eingartner K, Dopatka T, Kohl U, Basler H, Riedmiller H, 1997, Quality of life after cystectomy and urinary diversion: result of a retrospective interdisciplinar study. J Urol 158:778–785
Mansson A, Caruso A, Capovilla E, 2000, Quality of life after radical cystectomy and orthotopic bladder substitution. A comparison between Italian and Swedish men. BJU Int 85:26–31
Protogerou V, 2004, Modified S-pouch neobladder vs ileal conduit and a matched control population: a quality of life survey. BJ Urol 94:350–354
Peremenis P, Burkhard F, Kessler T, Gramann T, Studer UE, 2004, Ileal orthotopic bladder substitute combined with an afferent tubular segment: long-term upper urinary tract changes and voiding pattern. Eur Urol 46:604–609
Arata R, Saika T, Tsushima T, Abarzua F, Nasu Y, Kumon H, 2007, Orthotopic ileal neobladder versus sigmoid neobladder: a quality of life, QOL, survey. Acta Med Okayama 61:229–234
Gerharz EW, Mansson A, Hunt S, Skinner EC, Mansson W, 2005, Quality of life after cystectomy and urinary diversion: an evidence based analysis. J Urol 174:1729–1736
Kikuchi E, Horiguchi Y, Nakashima J, Ohigashi T, Oya M, Nakagawa K, Miyajima A, Murai M, 2006, Assessment of long – term quality of life using the FACT-BL questionnaire in patients with an ileal conduit, continent reservoir or orthotopic neobladder. Jpn J Clin Oncol 36:712–716
Saika T, Arata R, Tsushima T, Nasu Y, Suyama B, Takeda K, Ebara S, Manabe D, Kobayashi T, Tanimoto R, Kumon H, 2007, Health-related quality of life after radical cystectomy for bladder cancer in elderly patients with an ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir: a comperative questionnaire survey. Acta Med Okoyama 61:199–203
Schrier B, Laguna MP, van der Pal F, Isorna S, Witjes JA, 2005, Comparison of orthotopic sigmoid and ileal neobladders: continence and urodynamic parameters. Eur Urol 47:679–685
Sevin G, Soyupek S, Armagan A, Hoscan MB, Oksay T, 2004, Ileal orthotopic noebladder, modified Hautmann, via a shorter detubularized ileal segment: experience and results. BJU International 94:355–359
El Bahnasawy MS, Osman Y, Gomha MA, Shaaban AA, Ashamallah A, Ghoneim MA, 2000, Nocturnal enuresis in men with an orthotopic ileal reservoir: urodynamic evaluation. J Urol 164:10–13
Burckhard FC, Kessler TM, Springer J, Studer UE, 2006, Early and late urodynamic assessment of ileal orthotopic bladder substitutes combined with an afferent tubular segment. J Urol 175:2155–2161
El-Bahnasawy MS, Gomba MA, Shaaban AA, 2006, Urethral pressure profile following orthotopic neobladder: differences between nerve sparing and standard radical cystectomy techniques. J Urol 175:1759–1763
Thuroff JW, Mattiasson A, Andersen JT, Hedlund H, Hinman F, Hohenfellner M, Mansson W, Mundy AR, Rowland RG, Steven K, 1996, The standardization of terminology and assessment of functional characteristics of intestinal urinary reservoirs. BJ Urol 78:516–523
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Skinner DG, 1987, Editoral comment. J Urol 138:1154
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 307
EP 313
DI 10.1007/s12253-008-9099-8
PG 7
ER
PT J
AU Lakosi, F
Antal, G
Vandulek, Cs
Kovacs,
Garamvolgyi, R
Petnehazy, O
Bajzik, G
Hadjiev, J
Repa, I
Bogner, P
AF Lakosi, Ferenc
Antal, Gergely
Vandulek, Csaba
Kovacs, Arpad
Garamvolgyi, Rita
Petnehazy, Ors
Bajzik, Gabor
Hadjiev, Janaki
Repa, Imre
Bogner, Peter
TI Technical Feasibility of Transperineal MR-Guided Prostate Interventions in a Low-Field Open MRI Unit: Canine Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Interventional; Brachytherapy; MR-guidance
ID Prostate cancer; Interventional; Brachytherapy; MR-guidance
AB Magnetic resonance imaging (MRI) provides superior visualization of the prostate, its substructure, surrounding tissues, and, most important, focal lesions or cancer. The purpose of our canine study was to demonstrate the feasibility of a low-field (0.35 T) transperineal system that enables precise MR image guidance of prostate interventions. The canines were placed in the right lateral decubitus position. Template reconstruction, trajectory planning, contouring were based on T2-weighted FSE images. For image guidance and target confirmation, fast gradient spoiled-echo (FSPGR) sequence was used. MR compatible coaxial needles were manually inserted through the perineum to the base of the prostate. After satisfactory position was confirmed, brachytherapy catheters were placed through the coaxial needles. The mean deviation of the needle displacements was 2.9 mm with a median value of 2.7 mm. 97% of the errors were less than 4.0 mm. The needle placement accuracy was modelled by the Rayleigh distribution with a sigma value of 2.3 mm. Visual confirmation of needle placements was demonstrated on pathology tissue slices. The time needed for each step was: anaesthesia - 15 min, setup and positioning - 15 min, initial imaging - 15 min, template registration, projection - 15 min, contouring, trajectory planning, insertion of 12 needles - 60 min Based on our canine experiences our method seems to be a promising approach for performing feasible, accurate, reliable and high-quality prostate MR guidance within a reasonable time span.
C1 [Lakosi, Ferenc] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Antal, Gergely] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Vandulek, Csaba] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Kovacs, Arpad] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Garamvolgyi, Rita] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Petnehazy, Ors] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Bajzik, Gabor] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Hadjiev, Janaki] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Repa, Imre] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
[Bogner, Peter] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, H-7400 Kaposvar, Hungary.
RP Bogner, P (reprint author), Kaposi Mor Teaching Hospital, H-7400 Kaposvar, Hungary.
EM bogner.peter@sic.hu
CR Otto S, Kasler M, 2005, A hazai es nemzetkozi daganatos halalozasi es megbetegedesi mutatok alakulasa. Magyar Onkologia 49:99–107
Jereczek-Fossa BA, Orecchia R, 2007, Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for nonmetastatic prostate cancer. Radiother Oncol 84:197–215
Morton G, 2005, The emerging role of high-dose-rate brachytherapy for prostate cancer. Clin Oncol 17:219–227
Presti JC Jr, 2000, Prostate cancer: assessment of risk using digital rectal examination, tumor grade, prostate-specific antigen, and systematic biopsy. Radiol Clin North Am 38:49–58
Futterer J, 2007, MR imaging in the local staging of prostate cancer. Eur J Radiol 63:328–334
Morgan VA, Kyriazi S, Ashley SE et al, 2007, Evaluation of the potential of diffusion-weighted imaging in prostate cancer detection. Acta Radiol 48:695–703
Alonzi R, Padhani AR, Allen C, 2007, Dynamic contrast enhanced MRI in prostate cancer. Eur J Radiol 63:335–350
Mueller-Lisse UG, Scherr MK, 2007, Proton MR spectroscopy of the prostate. Eur J Radiol 63:351–360
Pouliot J, Kim Y, Lessard E et al, 2004, Inverse planning for HDR prostate brachytherapy used to boost dominant intraprostatic lesions defined by magnetic resonance spectroscopy imaging. Int J Radiat Oncol Biol Phys 59:1196–1207
Van Lin EN, Futterer JJ, Heymink SW et al, 2006, IMRT boost dose planning on dominant intraprostatic lesions: gold markerbased three-dimensional fusion of CT with dynamic contrastenhanced and 1H-spectroscopic MRI. Int J Radiat Oncol Biol Phys 65:291–303
Beyersdorff D, Winkel A, Hamm B et al, 2005, MR imagingguided prostate biopsy with a closed MR unit at 1.5 T: initial results. Radiology 234:576–581
D’Amico AV, Cormack R, Tempany CM et al, 1998, Real-time magnetic resonance image-guided interstitial brachytherapy in the treatment of select patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 42:507–515
Fischer GS, Di Maio SP, Haker SJ et al, 2006, A system for MRguided prostate interventions. Proceedings of 1st IEEE/RASDEMBS International Conference on Biomedical Robotics and Biomechatronics February 2006, 68–73
Di Maio SP, Pieper S, Chinzei K, 2007, Robot-assisted needle placement in open MRI: system architecture, integration and validation. Comput Aided Surg 12:15–24
Fischer GS, DiMaio SP, Iordachita II et al, 2007, Robotic assistant for transperineal prostate interventions in 3 T closed MRI. Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv 10:425–433
Engelhard K, Hollenbach HP, Kiefer B et al, 2006, Prostate biopsy in the supine position in a standard 1.5-T scanner under real time MR-imaging control using a MR-compatible endorectal biopsy device. Eur Radiol 16:1237–1243
Menard C, Susil RC, Choyke P et al, 2004, MRI-guided HDR prostate brachytherapy in standard 1.5 T scanner. Int J Radiat Oncol Biol Phys 59:1414–1423
Susil RC, Camphausen K, Choyke P et al, 2004, System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner. Magn Reson Med 52:683–687
Zangos S, Eichler K, Engelmann K et al, 2005, MR-guided transgluteal biopsies with an open low-field system in patients with clinically suspected prostate cancer: technique and preliminary results. Eur Radiol 15:174–182
Zangos S, Hercog C, Eichler K, 2007, MR-compatible assistance system for punction in a high-field system: device and feasibility of transgluteal biopsies of the prostate gland. Eur Radiol 17:1118– 1124
Potter R, Haie-Meder C, Van Limbergen E et al, 2005, Recommendations from gynaecological, GYN, GEC ESTRO working group, II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy—3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 78:67–77
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 315
EP 322
DI 10.1007/s12253-008-9111-3
PG 8
ER
PT J
AU Cai, L
Threadgill, DM
Wang, Y
Li, M
AF Cai, Li
Threadgill, D Michael
Wang, Yalan
Li, Ming
TI Effect of Poly (ADP-ribose) Polymerase-1 Inhibition on the Proliferation of Murine Colon Carcinoma CT26 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PARP-1; NF-κB; Proliferation; Colon carcinoma; In vitro
ID PARP-1; NF-κB; Proliferation; Colon carcinoma; In vitro
AB To investigate effect of poly (ADP-ribose) polymerase inhibition on the proliferation of CT26 cells in vitro and the mechanism of this effect. CT26 cells were treated with a range of concentrations of 5-Aminoisoquinolin-1-one (PARP inhibitor) in vitro. MTT assays and flow cytometry were used to determine the proliferation and cell cycle distribution, respectively, of the cells. The expression of PARP-1 was investigated by Western blot. The binding of Nuclear Factor-κB to DNA was detected by electrophoretic mobility shift assay. The proliferation of CT26 cells was significantly inhibited by 5-AIQ induced PARP inhibition in a dose-dependent manner. Proliferation was inhibited by 17.5% at 100 μM 5-AIQ, by 27.6% at 500 μM 5-AIQ and by 39.9% at 1000 μM (P<0.05). After treatment with 5-AIQ, the proportion of cells in G0/Gl phases increased and the proportion of cells in S phase decreased. The expression of PARP-1 was attenuated in 5-AIQ-treated CT26 cells (P<0.05) and the binding of NF-κB to DNA binding was similarly diminished (P<0.05). These results suggest that PARP inhibition reduced the proliferation of CT26 cells in vitro and influences the cell cycle. This inhibition is mediated by inhibiting PARP-1, which then diminishes the activity of NF-κB.
C1 [Cai, Li] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Threadgill, D Michael] University of Bath, Department of Pharmacy & Pharmacology, BA2 7AY Claverton Down Bath, UK.
[Wang, Yalan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Li, Ming] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
RP Wang, Y (reprint author), Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
EM wangyalan074@126.com
CR Cuzzocrea S, Mazzon E, Di Paola R et al, 2004, 5-Aminoisoquinolinone reduces colon injury by experimental colitis. Naunyn Schmiedebergs Arch Pharmacol 370:464–473
Mota-Filipe H, Sepodes B, McDonald MC et al, 2002, The novel PARP inhibitor 5-aminoisoquinolinone reduces the liver injury caused by ischemia and reperfusion in the rat. Med Sci Monit 8: BR444–453
Cuzzocrea S, McDonald MC, Mazzon E et al, 2002, Effects of 5- aminoisoquinolin-one, a water-soluble, potent inhibitor of the activity of poly, ADP-ribose, polymerase, in a rodent model of lung injury. Biochem Pharmacol 63:293–304
Nosho K, Yamamoto H, Mikami M et al, 2006, Overexpression of poly(ADP-ribose, polymerase-1, PARP-1, in the early stage of colorectal carcinogenesis. Eur J Cancer 42:2374–81
Lockett KL, Hall MC, Xu J, 2004, The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function. Cancer Res 64:6344–6348
Albert JM, Cao C, Kim KW et al, 2007, Inhibition of poly(ADPribose, polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin. Cancer Res. 13:3033–3042
Kang YH, Yi MJ, Kim MJ et al, 2004, caspase-independent cell death by arsenic trioxide in human cervical cancer cells: reactive oxygen species-mediated poly(ADP-ribose, polymerase-1 activation signals apoptosis-inducing factor release from mitochondria. Cancer Res. 64:8960–8967
Hao LX, Wang YL, Li YY, 2006, Correlation of PARP expression with P-selectin and ICAM-1 expression in colorectal carcinoma. Basic Med Sci Clinics 26:882–887
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 323
EP 328
DI 10.1007/s12253-008-9116-y
PG 6
ER
PT J
AU Takacs, T
Paszt, A
Szentpali, K
Ormandi, K
Lazar, M
Palka, I
Kahan, Zs
Lazar, Gy
AF Takacs, Tibor
Paszt, Attila
Szentpali, Karoly
Ormandi, Katalin
Lazar, Mate
Palka, Istvan
Kahan, Zsuzsanna
Lazar, Gyorgy
TI Importance of Sentinel Lymph Node Biopsy in Surgical Therapy of in situ Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Ductal in situ breast cancer; Microinvasion; Isotope localization; Sentinel lymph node biopsy; Lymph node metastasis
ID Ductal in situ breast cancer; Microinvasion; Isotope localization; Sentinel lymph node biopsy; Lymph node metastasis
AB The aim of this retrospective study was to determine the rate of sentinel lymph node (SLN) positivity in patients with a final diagnosis of ductal in situ cancer (DCIS) of the breast. Between October 2002 and January 2007, 57 patients with DCIS underwent wide excision after radio-guided lesion localization; 53 of them (53/57, 93%) had participated in simultaneous SLN mapping. SLNs were analysed by 250-micron step-sectioning with haematoxylin and eosin staining and immunohistochemical evaluation. The histologic investigation verified pure breast DCIS in 44 cases (44/57, 77.2%), DCIS with microinvasion in eight cases (8/57, 14%) and lobular in situ breast cancer in five cases (5/57, 8.8%). SLNs were identified in 49 cases (49/53, 92.5%) and removed in 48 cases (48/53, 90.6%), i.e. an average of 1.6 SLNs per patient. In four patients (4/53, 7.6%), the SLN biopsy was unsuccessful because of the failure of the radiocolloid substance to migrate. In these cases, axillary sampling was performed. In one case (1/53, 1.9%), only a parasternal SLN was detected; this was not removed. Histologic analysis of the SLNs and the axillary lymph nodes with haematoxylin and eosin or cytokeratin immunohistochemistry did not prove the presence of metastases. The international data and our present results suggest that routine SLN biopsy is not to be recommended in pure DCIS cases. If the final histology verifies an invasive or microinvasive tumour, or if mastectomy is to be performed, SLN mapping is suggested.
C1 [Takacs, Tibor] University of Szeged, Department of Surgery, Pecsi u. 4, H-6720 Szeged, Hungary.
[Paszt, Attila] University of Szeged, Department of Surgery, Pecsi u. 4, H-6720 Szeged, Hungary.
[Szentpali, Karoly] University of Szeged, Department of Surgery, Pecsi u. 4, H-6720 Szeged, Hungary.
[Ormandi, Katalin] University of Szeged, Department of RadiologySzeged, Hungary.
[Lazar, Mate] University of Szeged, Department of RadiologySzeged, Hungary.
[Palka, Istvan] University of Szeged, Department of PathologySzeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of Surgery, Pecsi u. 4, H-6720 Szeged, Hungary.
RP Lazar, Gy (reprint author), University of Szeged, Department of Surgery, H-6720 Szeged, Hungary.
EM lg@surg.szote.u-szeged.hu
CR Cody HS 3rd, Klauber-DeMore N, Borgen PI, Van Zee KJ, 2001, Is it really duct carcinoma in situ? Ann surg oncol 8:617–619
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Mittendorf EA, Arciero CA, Gutchell V, Hooke J, Shriver CD, 2005, Core biopsy diagnosis of ductal carcinoma in situ: an indication for sentinel lymph node biopsy. Curr Surg 62:253–257
Moran CJ, Kell MR, Kerin MJ, 2005, The role of sentinel lymph node biopsy in ductal carcinoma in situ. Eur j surg oncol 31:1105–1111
Zavagno G, Carcoforo P, Marconato R, Franchini Z, Scalco G, Burelli P, Pietrarota P, Lise M, Mencarelli R, Capitanio G, Ballarin A, Pierobon ME, Marconato G, Nitti D, 2005, Role of axillary sentinel lymph node biopsy in patient with pure ductal carcinoma in situ of the breast. BMC Cancer 5:28–34
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Broekhuizen LN, Wijsman JH, Peterse JL, Rutgers EJ, 2006, The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast. Eur J Surg Oncol 32:502–506
Kelly TA, Kim JA, Patrick R, Grundfest S, Crowe JP, 2003, Axillary lymph node metastases in patient with a final diagnosis of ductal carcinoma in situ. Am J Surg 186:368–370
Veronesi P, Intra M, Vento AR, Naninato P, Caldarella P, Paganelli G, Viale G, 2005, Sentinel lymph node biopsy for localised ductal carcinoma in situ? The Breast 14:520–522
Torok K, Peley G, Matrai Z, Bidlek M, Szabo E, Sinkovics I, Polgar C, Farkas E, Orosz Z, Koves I, 2006, The role of sentinel lymph node biopsy for staging patients with ductal carcinoma in situ of the breast. Magy Seb 59:173–178
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El-Tamer M, Chun J, Gill M, Bassi D, Lee S, Hibshoosh H, Mansukhani M, 2005, Incidence and clinical significance of lymph node metastasis detected by cytokeratin immunhistochemical staining in ductal carcinoma in situ. Ann Surg Oncol 12:254–259
Dupont EL, McCann C, Cox CE, 1999, Ductal carcinoma in situ of the breast cancer control 6(3):264–271
Schwartz GF, Solin LJ, Olivotto IA, Ernster VL, Pressman P, Consensus Conference Committee, 2000, Consensus conference on the treatment of in situ ductal carcinoma of the breast April 22– 25. 1999. Cancer 88:946–954
Intra M, Veronesi P, Mazzarol G, Galimberti V, Luini A, Sacchini V, Trifiro G, Gentilini O, Pruneri G, Naninato P, Torres F, Paganelli G, Viale G, Veronesi U, 2003, Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. Archives of Surgery 138:309–313
Leidenius M, Salmenkivi K, von Smitten K, Heikkila P, 2006, Tumour-positive sentinel node findings in patients with ductal carcinoma in situ. J Surg Oncol 94:380–384
Mabry H, Giuliano AE, Silverstein MJ, 2006, What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma ins situ? Am J Surg 192:455–457
Katz A, Gage I, Evans S, Shaffer M, Fleury T, Smith F, Flax R, Drogula C, Petrucci P, Magnant C, 2006, Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer. Am J Surg 191:761–766
Wilkie C, White L, Dupont E, Cantor A, Cox CE, 2005, An update of sentinel lymph node mapping in patients with ductal carcinoma in situ. Am J Surg 190:563–566
Farkas EA, Stolier AJ, Teng SC, Bolton JS, Fuhrman GM, 2004, An argument against routine sentinel node mapping for DCIS. Am Surg 70:13–18
Camp R, Feezor R, Kasraeian A, Cendan J, Schell S, Wilkinson E, Copeland E, Lind S, 2005, Sentinel lymph node biopsy for ductal carcinoma in situ: an evolving approach at the University of Florida. Breast J 11:394–397
Zavagno G, Belardinelli V, Marconato R, Carcoforo P, Franchini Z, Scalco G, Burelli P, Pietrarota P, Mencarelli R, Marconato G, Nitti D, 2007, Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion. The Breast 16:146–151
Cserni G, Ambrozay E, Serenyi P, Bori R, Lorincz M, Lorand K, 2005, A nem operativ patologiai emlodiagnosztika eredmenyei. Magy Radiol 79:178–183
Zujewski J, Eng-Wong J, 2005, Sentinel lymph node biopsy in the management of ductal carcinoma in situ. Clin Breast Cancer 6:216–222
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 329
EP 333
DI 10.1007/s12253-008-9123-z
PG 5
ER
PT J
AU Reti, A
Barna, G
Pap,
Adleff, V
Komlosi, LV
Jeney, A
Kralovanszky, J
Budai, B
AF Reti, Andrea
Barna, Gabor
Pap, Eva
Adleff, Vilmos
Komlosi, L Viktor
Jeney, Andras
Kralovanszky, Judit
Budai, Barna
TI Enhancement of 5-Fluorouracil Efficacy on High COX-2 Expressing HCA-7 Cells by Low Dose Indomethacin and NS-398 but not on Low COX-2 Expressing HT-29 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE COX-2; PGE2; HT-29 and HCA-7 cells; 5-fluorouracil; Indomethacin; NS-398; Cell cycle phase
ID COX-2; PGE2; HT-29 and HCA-7 cells; 5-fluorouracil; Indomethacin; NS-398; Cell cycle phase
AB The antiproliferative effect of 5-fluorouracil (5-FU) in the presence of low dose non-steroidal antiinflammatory drugs (NSAIDs) on high cyclooxygenase-2 (COX-2)-expressing HCA-7 and low COX-2-expressing HT-29 colon carcinoma cell lines was investigated. Pharmacogenetic parameters were studied to characterize the 5-FU sensitivity of the two cell lines. Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms were determined by PCR analysis. Cell proliferation was measured by SRB assay, cell cycle distribution and apoptosis by FACS analysis. Cyclooxygenase expression was detected by Western blot and also by fluorescence microscopy. Prostaglandin E2 (PGE2) levels were investigated with ELISA kit. The HT-29 cell line was found to be homozygous for TS 2R and 1494ins6 and T homozygous for MTHFR 677 polymorphisms predicting high 5-FU sensitivity (IC50: 10 μM). TS 3R homozygosity, TS 1496del6 and MTHFR 677CT heterozygosity may explain the modest 5-FU sensitivity (IC50: 1.1 mM) of the HCA-7 cell line. Indomethacin and NS-398 (10 μM and 1.77 μM, respectively) reduced the PGE2 level in HCA-7 cells (>90%). Low concentrations of NSAIDs without antiproliferative potency increased the S-phase arrest and enhanced the cytotoxic action of 5-FU only in HCA-7 cells after 48-hours treatment. The presented data suggested that the enhancement of 5-FU cytotoxicity by indomethacin or NS-398 applied in low dose is related to the potency of NSAIDs to modulate the cell-cycle distribution and the apoptosis; however, it seems that this effect might be dependent on cell phenotype, namely on the COX-2 expression.
C1 [Reti, Andrea] National Institute of OncologyBudapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Pap, Eva] National Institute of OncologyBudapest, Hungary.
[Adleff, Vilmos] National Institute of OncologyBudapest, Hungary.
[Komlosi, L Viktor] National Institute of OncologyBudapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kralovanszky, Judit] National Institute of OncologyBudapest, Hungary.
[Budai, Barna] National Institute of OncologyBudapest, Hungary.
RP Kralovanszky, J (reprint author), National Institute of Oncology, Budapest, Hungary.
EM kralo@oncol.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 335
EP 344
DI 10.1007/s12253-008-9126-9
PG 10
ER
PT J
AU Aktas, S
Kargi, A
Olgun, N
Diniz, G
Erbay, A
Vergin, C
AF Aktas, Safiye
Kargi, Aydanur
Olgun, Nur
Diniz, Gulden
Erbay, Ayse
Vergin, Canan
TI Prognostic Significance of Cell Proliferation and Apoptosis-Regulating Proteins in Epstein-Barr Virus Positive and Negative Pediatric Non-Hodgkin’s Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pediatric non-Hodgkin’s lymphoma; Epstein Barr virus; Apoptosis; Proliferation; Prognosis
ID Pediatric non-Hodgkin’s lymphoma; Epstein Barr virus; Apoptosis; Proliferation; Prognosis
AB Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Virus (EBV) are contemporary issues in pediatric non-Hodgkin’s lymphoma (pNHL). In this study prognostic or pathogenetic role of EBV latent infection, proliferating activity, and apoptosisregulating proteins in pNHL were explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, bax, fas, c-myc, p53 and apoptotic index by TUNEL method were explored in 70 pNHL cases and evaluated statistically. Of the 70 cases evaluated, 24 were female and 46 were male. Seven cases were stage I/II and 63 cases were stage III/IV. The mean age was 7.16±3.72(1–15). EBV was positive in (25.7%) cases. Overall survival was 82%, while event free survival was 75%. Bax was expressed in 40% of the cases, while the expression of bcl-2,was 50%, survivin 42.9%, p53 8.6%, fas 18.6% and c-myc in 45.7%. Mean apoptotic index was 131.29±96.69 per 5,000 cells. Mean proliferation index was 55.97% (12–92%). Fas positivity was high in EBV positive cases (p=0.0001). EBV positivity was not related with prognosis. Apoptotic index was found to be an independent prognostic factor (p=0.017). Our results suggest that apoptosis-regulating proteins have a role in the pathogenesis of pNHL. EBV was correlated with apoptotic index and fas, bcl-2. No correlation was observed with proliferation index and studied factors. High apoptotic index was related with good prognosis.
C1 [Aktas, Safiye] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Bornova, 125/7 sokak Brickent A-3, 35150 Izmir, Turkey.
[Kargi, Aydanur] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Bornova, 125/7 sokak Brickent A-3, 35150 Izmir, Turkey.
[Olgun, Nur] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Diniz, Gulden] Dr Behcet Uz Children’s Research Hospital, Specialist in PathologyIzmir, Turkey.
[Erbay, Ayse] Dr Behcet Uz Children’s Research Hospital, Specialist in Pediatric OncologyIzmir, Turkey.
[Vergin, Canan] Dr Behcet Uz Children’s Research Hospital, Pediatric HematologyIzmir, Turkey.
RP Aktas, S (reprint author), Dokuz Eylul University, Faculty of Medicine, Department of Pathology, 35150 Izmir, Turkey.
EM safiyeaktas@yahoo.com
CR Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD, 2000, The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting—Airlie House, Virginia, November, 1997. Hematol J 1(1):53–66
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Cairo MS, Sposto R, Perkins SL, Meadows AT, Hoover-Regan ML, Anderson JR, Siegel SE, Lones MA, Tedeschi-Blok N, Kadin ME, Kjeldsberg CR, Wilson JF, Sanger W, Morris E, Krailo MD, Finlay JL, 2003, Burkitt's and Burkitt-like lymphoma in children and adolescents: a review of the Children's Cancer Group experience. Br J Haematol 120(4):660–670
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Hirose Y, Fukushima T, Masaki Y, Shimoyama K, Karasawa H, Ogawa N,Wano Y, 2004, Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell lymphoma and an anaplastic variant of a diffuse large B-cell type of non-Hodgkin's lymphoma and strongly expressing p53 protein. Int J Hematol 79, 3):260–265
Camilleri-Broet S, Camparo P, Mokhtari K, Hoang-Xuan KH, Martin A, Arborio M, Hauw JJ, Raphael M, 2000, Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients. Mod Pathol 13(2):158–165
Gutierrez MI, Cherney B, Hussain A, Mostowski H, Tosato G, Magrath I, Bhatia K, 1999, Bax is frequently compromised in Burkitt's lymphomas with irreversible resistance to Fas-induced apoptosis. Cancer Res 59(3):696–703
Faqing T, Zhi H, Liqun Y, Min T, Huanhua G, Xiyun D, Ya C, 2005, Epstein-Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of Survivin in nasopharyngeal carcinoma. Exp Oncol 27(2):96–101
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Idenoue S, Hirohashi Y, Torigoe T, Sato Y, Tamura Y, Hariu H, Yamamoto M, Kurotaki T, Tsuruma T, Asanuma H, Kanaseki T, Ikeda H, Kashiwagi K, Okazaki M, Sasaki K, Sato T, Ohmura T, Hata F, Yamaguchi K, Hirata K, Sato N, 2005, A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins. Clin Cancer Res 11(4):1474–1482
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Pagnano KB, Vassallo J, Lorand-Metze I, Costa FF, Saad ST, 2001, p53, Mdm2, and c-Myc overexpression is associated with a poor prognosis in aggressive non-Hodgkin's lymphomas. Am J Hematol 67(2):84–92
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 345
EP 350
DI 10.1007/s12253-008-9127-8
PG 6
ER
PT J
AU Liu, Y
Guo, F
Dai, M
Wang, D
Tong, Y
Huang, J
Hu, J
Li, G
AF Liu, Yan
Guo, Fengjie
Dai, Miao
Wang, Di
Tong, Yongqing
Huang, Jian
Hu, Jinyue
Li, Guancheng
TI Gammaaminobutyric Acid A Receptor Alpha 3 Subunit is Overexpressed in Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; GABRA3; Immunohistochemistry; In silico; RT-PCR
ID Cancer; GABRA3; Immunohistochemistry; In silico; RT-PCR
AB The identification of tumor-associated antigens, which are specifically expressed in cancer tissues, is very important for immunotherapy of lung cancer. We have combined the in silico screening and experimental verifying to identify genes that are differently expressed in cancers compared with their corresponding normal tissues. Using these methods, we have identified that GABRA3 gene was overexpressed in lung cancer and rarely expressed in other cancers. Furthermore, GABRA3 protein expression was significantly higher in the lower grade of lung cancer. It may compose functional GABA-gated channel with other subunits. This study demonstrated GABRA3 could be a potential biomarker for diagnosis of lung cancer, and GABAA receptors may play an important role in cancer differentiation.
C1 [Liu, Yan] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
[Guo, Fengjie] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
[Dai, Miao] Affiliated Hospital of Weifang Medical University, 261031 Weifang, Shandong Province, China.
[Wang, Di] Central South University, Xiangya Hospital, 410078 Changsha, Hunan Province, China.
[Tong, Yongqing] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
[Huang, Jian] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
[Hu, Jinyue] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
[Li, Guancheng] Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, Hunan Province, China.
RP Li, G (reprint author), Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, China.
EM libsun@163.com
CR Toronto, Canada, Canadian Cancer Society/National Cancer Institute of Canada, 2006, Canadian Cancer Statistics
Carbone DP, 1997, The biology of lung cancer. Semin Oncol 24, 4):388–401
Chen Y, Miller C, Mosher R et al, 2003, Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Res 63, 8):1927–1935
Takahashi M, Yang XJ, Sugimura J et al, 2003, Molecular subclassification of kidney tumors and the discovery of new diagnostic markers. Oncogene 22(43):6810–6818
Reis EM, Ojopi EP, Alberto FL et al, 2005, Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer. Cancer Res 65(5):1693–1699
Vinals C, Gaulis S, Coche T, 2001, Using in silico transcriptomics to search for tumor-associated antigens for immunotherapy. Vaccine 19(17–19):2607–2614
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Akio T, Masayo H, Hidetoshi E et al, 2007, γ-aminobutyric acid, GABA, stimulates pancreatic cancer growth through overexpressing GABAA receptor π subunit. Cancer Res 67(20): 9704–9712
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Azuma H, Inamoto T, Sakamoto T et al, 2003, γ-Aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism. Cancer Res 63(23):8090–8096
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 351
EP 358
DI 10.1007/s12253-008-9128-7
PG 8
ER
PT J
AU Akkiprik, M
Sonmez, O
Gulluoglu, MB
Caglar, BH
Kaya, H
Demirkalem, P
Abacioglu, U
Sengoz, M
Sav, A
Ozer, A
AF Akkiprik, Mustafa
Sonmez, Ozgur
Gulluoglu, M Bahadir
Caglar, B Hale
Kaya, Handan
Demirkalem, Pakize
Abacioglu, Ufuk
Sengoz, Meric
Sav, Aydin
Ozer, Ayse
TI Analysis of p53 Gene Polymorphisms and Protein Over-expression in Patients with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53 polymorphisms; Haplotype; Breast cancer
ID p53 polymorphisms; Haplotype; Breast cancer
AB p53 polymorphic variants play an important role in the determination of tumor phenotype and characteristics in breast cancer. In this study, we examined three common polymorphisms in p53 gene and their haplotype combinations to assess their potential association with inherited predisposition to breast cancer development, in relations with the protein over-expression and patients’ demographic data. A total of 99 patients with breast cancer and 107 agematched healthy controls were included in the study. Genotypes were determined using PCR-RFLP and DNA sequencing techniques. Evaluation of p53 protein overexpression was also examined by immunohistochemistry. Among three polymorphisms, increased codon 72 Pro allele frequency (p=0.0067) and the presence of Pro allele were found to be significantly associated with breast cancer (p=0.013). A significant risk was also found in subjects with combinations of specific haplotypes and genotypes. Most of breast cancer women especially younger than 50 years carry at least one p53 polymorphism (p=0.001). There was no any association between these three p53 polymorphisms and the protein over-expression, separately or in interaction, with breast cancer. In conclusion, presence of proline allele at codon 72 alone, and its special combinations with other two polymorphisms appear to be a significant risk factor for breast cancer. Determination of well-known p53 polymorphisms might be a good predictor for breast cancer development especially in women younger than 50 years.
C1 [Akkiprik, Mustafa] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad, No: 49, Haydarpasa, 34668 Istanbul, Turkey.
[Sonmez, Ozgur] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad, No: 49, Haydarpasa, 34668 Istanbul, Turkey.
[Gulluoglu, M Bahadir] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
[Caglar, B Hale] Marmara University, School of Medicine, Department of Radiation OncologyIstanbul, Turkey.
[Kaya, Handan] Marmara University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Demirkalem, Pakize] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
[Abacioglu, Ufuk] Marmara University, School of Medicine, Department of Radiation OncologyIstanbul, Turkey.
[Sengoz, Meric] Marmara University, School of Medicine, Department of Radiation OncologyIstanbul, Turkey.
[Sav, Aydin] Marmara University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Ozer, Ayse] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad, No: 49, Haydarpasa, 34668 Istanbul, Turkey.
RP Akkiprik, M (reprint author), Marmara University, School of Medicine, Department of Medical Biology, 34668 Istanbul, Turkey.
EM makkiprik@marmara.edu.tr
CR Dunning AM, Healey CS, Pharoah PD et al, 1999, A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 8:843–854
Levine AJ, Momand J, Finlay CA, 1991, The p53 tumour supressor gene. Nature 351:453–456
Nigro JM, Baker SJ, Preisinger AC et al, 1989, Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708
Olivier M, Langerod A, Carrieri P et al, 2006, The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res 12:1157–1167
Olivier M, Eeles R, Hollstein M et al, 2002, The IARC TP53 Database: new online mutation analysis and recommendations to users. Hum Mutat 19:607–614
Weston A, Pan CF, Ksieski HB et al, 1997, p53 haplotype determination in breast cancer. Cancer Epidemiol Biomarkers Prev 6:105–112
Wang-Gohrke S, Rebbeck TR, Besenfelder W et al, 1998, p53 germline polymorphisms are associated with an increased risk for breast cancer in German women. Anticancer Res 18:2095– 2099
Papadakis EN, Dokianakis DN, Spandidos DA, 2000, p53 codon 72 polymorphisms as a risk factor in the development of breast cancer. Mol Cell Bio Res Comm 3:389–392
Kalemi TG, Lambropoulos AF, Gueorguiev M et al, 2005, The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece. Cancer Lett 222:57–65
Sjalander A, Birgander R, Hallmans G et al, 1996, p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis 17:1313–1316
Dumont P, Leu JIJ, Pietra ACD et al, 2003, The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33:357–365
Marin MC, Jost CA, Brooks LA et al, 2000, A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet 25:47–54
Gemignani F, Moreno V, Landi S et al, 2004, A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene 23:1954–1956
Peller S, Kopilova Y, Slutzki S et al, 1995, A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility. DNA Cell Biol 14:983–990
Weston A, Wolff MS, Morabia A, 1998, True extended haplotypes of p53: indicators of breast cancer risk. Cancer Genet Cytogenet 102:153–154
Sjalander A, Birgander R, Kivela A et al, 1995, p53 polymorphisms and haplotypes in different ethnic groups. Hum Hered 45:144–149
Wu X, Zhao H, Amos CI et al, 2002, p53 genotypes and haplotypes associated with lung cancer susceptibility and ethnicity. J Natl Cancer Inst 94:681–690
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Soong R, Iacopetta BJ, 1997, A rapid and nonisotopic method for the screening and sequencing of p53 gene mutations in formalin-fixed, paraffin-embedded tumors. Mod Pathol 10:252– 258
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Khadang B, Fattahi MJ, Talei A et al, 2007, Polymorphism of TP53 codon 72 showed no association with breast cancer in Iranian women. Cancer Genet Cytogenet 173:38–42
Franekova M, Zubor P, Stanclova A et al, 2007, Association of p53 polymorphisms with breast cancer: a case-control study in Slovak population. Neoplasma 54:155–161
Buyru N, Tigli H, Dalay N, 2003, p53 codon 72 polymorphism in breast cancer. Oncol Rep 10:711–714
Langerod A, Bukholm IRK, Bregard A et al, 2002, The TP53 Codon 72 polymorphism may affect the function of TP53 mutation in breast carcinomas but not in colorectal carcinomas. Cancer Epidemiol Biomarkers Prev 11:1684–1688
Suspitsin EN, Buslov KG, Grigoriev MY et al, 2003, Evidence against involvement of p53 polymorphism in breast cancer predisposition. Int J Cancer 103:431–433
Wang-Gohrke S, Becher H, Kreienberg R et al, 2002, Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk or breast cancer by the age of 50 years. Pharmacogenetics 12:269–272
Wegman P, Stal O, Askmalm MS et al, 2006, p53 polymorphic variants at codon 72 and the outcome of therapy in randomized breast cancer patients. Pharmacogenet Genomics 16:347–351
Tan XL, Popanda O, Ambrosone CB et al, 2006, Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients. Breast Cancer Res Treat 97:255–262
Costa S, Pinto D, Pereira D et al, 2008, Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms in prediction of susceptibility on breast cancer. BMC Cancer 8:32
Bartley AN, Ross DW, 2002, Validation of p53 immunohistochemistry as a prognostic factor in breast cancer in clinical practice. Arch Pathol Lab Med 126:456–458
Rolland P, Spendlove I, Madjid Z et al, 2007, The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer. Int J Cancer 120:1311–1317
Yamashita H, Toyama T, Nishio M et al, 2006, p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer. Breast Cancer Res 8:R48
Roos MA, de Bock GH, de Vries J et al, 2007, p53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast. J Surg Res 140:109–114
Kai K, Nishimura R, Arima N et al, 2006, p53 expression status is a significant molecular marker in predicting the time to endocrine therapy failure in recurrent breast cancer: a cohort study. Int J Clin Oncol 11:426–433
Gammon MD, Hibshoosh H, Terry MB et al, 1999, Cigarette smoking and other risk factors in relation to p53 expression in breast cancer among young women. Cancer Epidemiol Biomarkers Prev 8:255–263
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 359
EP 368
DI 10.1007/s12253-008-9129-6
PG 10
ER
PT J
AU Han, Zd
Bi, Xch
Qin, Wj
He, Hch
Dai, Qsh
Zou, J
Ye, Yk
Liang, Yx
Zeng, Gh
Chen, Zn
Zhong, Wd
AF Han, Zhao-dong
Bi, Xue-cheng
Qin, Wei-jun
He, Hui-chan
Dai, Qi-shan
Zou, Jun
Ye, Yong-kang
Liang, Yu-xiang
Zeng, Guo-hua
Chen, Zhi-nan
Zhong, Wei-de
TI CD147 Expression Indicates Unfavourable Prognosis in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; CD147; Clinical pathology; Diagnosis; Prognosis
ID Prostate cancer; CD147; Clinical pathology; Diagnosis; Prognosis
AB Extracellular matrix metalloproteinase inducer (EMMPRIN, also named as CD147) is a multifunctional membrane glycoprotein over-expressed in many kinds of human solid tumors. It has been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological characteristics of the expression of CD147 in human prostate cancer (PCa), and to evaluate its clinical significance in the histologic classification and prognosis of PCa. CD147 protein expression in paraffin-embedded specimens gathered from 62 cases of PCa and 30 cases of benign prostatic hyperplasia (BPH) were detected by the method of immunohistochemistry. The association of CD147 protein expression with the clinicopathological characteristics and with the prognosis of PCa was subsequently assessed. CD147 expression were positively expressed in 51/62 (82.3%) of PCa and 4/30 (13.3%) of BPH cases, respectively. The positive expression rate of CD147 in PCa tissues was significantly higher than that in BPH. The positive expression of CD147 was dramatically associated with TNM grade (p<0.001), the depth of the prostatic wall invasion (p=0.008), GLEASON Score (p=0.001) and Histologic grade (p=0.001). The patients with CD147 expression were associated with a poor prognosis of PCa (p=0.01) and the survival rate of the patients with a strong positive expression of CD147 was the lowest (p=0.01). The results suggest that the expression of CD147 may be an important feature of PCa and the detection of its expression may benefit us in the prediction of the prognosis of PCa.
C1 [Han, Zhao-dong] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Bi, Xue-cheng] Southern Medical University, #1 Pan Fu Road, 510180 Guangzhou, China.
[Qin, Wei-jun] Fourth Military Medical University, Department of Cell Biology & Cell Engineering Research CentreXi’an, China.
[He, Hui-chan] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Dai, Qi-shan] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Zou, Jun] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Ye, Yong-kang] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Liang, Yu-xiang] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
[Zeng, Guo-hua] Guangzhou Medical College, First Affiliated HospitalGuangzhou, China.
[Chen, Zhi-nan] Fourth Military Medical University, Department of Cell Biology & Cell Engineering Research CentreXi’an, China.
[Zhong, Wei-de] Guangzhou Medical College, First Affiliated Hospital, #1 Pan Fu Road, 510180 Guangzhou, China.
RP Zhong, Wd (reprint author), Guangzhou Medical College, First Affiliated Hospital, 510180 Guangzhou, China.
EM wdezhong@21cn.com
CR Schrgder FH, Wildhagen MF, ERSPC, 2001, Screening for prostate cancer: evidence and perspectives. BJU Int 88:811–817
Holmberg L, Bill-Axelson A, Helgesen F, 2002, A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. New Eng J Med 347:781–789
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Kehinde EO, Maghrebi MA, Anim JT, 2008, The importance of determining the aggressiveness of prostate cancer using serum and tissue molecular markers. Can J Urol 15:3967–3974
Wang L, Wu G, Yu L, Yuan J, Fang F, Zhai Z et al, 2006, Inhibition of CD147 expression reduces tumor cell invasion in human prostate cancer cell line via rna interference. Cancer Biology & Therapy 5:608–614
Gabison EE, Mourah S, Steinfels E et al, 2005, Differential expression of extracellular matrix metalloproteinase inducer, CD147, in normal and ulcerated corneas. Am. J. Pathol 166:209–219
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Sidhu SS, Mengistab AT, Tauscher AN, LaVail J, Basbaum C, 2004, The microvesicle as a vehicle for EMMPRIN in tumorstromal interactions. Oncogene 23:956–963
Millimaggi D, Mari M, D’Ascenzo S, Carosa E, Jannini EA, Zucker S et al, 2007, Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 9:349– 357
Nabeshima K, Iwasaki H, Koga K, Hojo H, Suzumiya J, Kikuchi M, 2006, Emmprin, basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int. 56:359–367
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Tang Y, Kesavan P, Marian T, 2004, Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer, EMMPRIN, expressio and matrix metalloproteinase- dependent generation of soluble EMMPRIN. Mol Cancer Res 2:73–80
Kanekura T, Chen X, Kanzaki T, 2002, Basigin, CD147, is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer 99:520–528
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 369
EP 374
DI 10.1007/s12253-008-9131-z
PG 6
ER
PT J
AU Miltenyi, Zs
Toth, J
Gonda, A
Tar, I
Remenyik,
Illes,
AF Miltenyi, Zsofia
Toth, Judit
Gonda, Andrea
Tar, Ildiko
Remenyik, Eva
Illes, Arpad
TI Successful Immunomodulatory Therapy in Castleman Disease with Paraneoplastic Pemphigus Vulgaris
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Castleman disease; Immunmodulatory; PET/CT
ID Castleman disease; Immunmodulatory; PET/CT
AB Castleman disease is a rare lymphoproliferative disorder. The clinical signs and symptoms of the disease are primarily mediated by cytokines, especially interleukin-6. We presented the case of a young female. In May 2004, a 30-year-old otherwise healthy looking woman presented with oral ulcerations resistant to topical and systemic antibiotic and antimycotic treatment. Bullous mucosal lichen or pemphigus vulgaris were suspected. Histological examination and direct and indirect immunofluorescence confirmed the diagnosis of pemphigus. Search for neoplasm revealed a retroperitoneal Castleman tumour sized 15×6×5 cm in the abdominal MRI. The tumour was a bleeder, so the removal was partial. Histological examination showed hyalin hypervascular Castleman disease. Considering her young, fertile age and the multicentric Castleman disease, non-cytostatic immunomodulatory therapy was started including steroid, cyclosporine-A and thalidomide treatment. The control abdominal CT showed a small residual tumour on the bladder. The residual tumour was removed in repeated surgery. At this time the histological examination showed transient type tumour between plasma cell and vascular variant. Currently, i.e. 4 years after the onset of the disease. 18FDG PET/CT examination showed low metabolic active mass in the right iliacal region, but our patient had no symptoms or complaints. She is on 200 mg thalidomide a day and no tumour progression can be seen. Castleman disease can be successfully treated with non-cytostatic immunomodulatory therapy.
C1 [Miltenyi, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
[Toth, Judit] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Gonda, Andrea] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Tar, Ildiko] University of Debrecen, Faculty of Dentistry, Department of PeriodontologyDebrecen, Hungary.
[Remenyik, Eva] University of Debrecen, Department of DermatologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
RP Miltenyi, Zs (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Debrecen, Hungary.
EM mil03@freemail.hu
CR Castleman B, Thowne VW, 1954, Case records of the Massachuetts General Hospital weekly clinicopathological exercises: Case 40011. N Eng J Med 250:26–30
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Casper C, 2005, The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 129:3–17
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Waterston A, Bower M, 2004, Fifty years of multicentric Castleman’s disease. Acta Oncologica 43:698–704
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Nishimoto N, Kanakura Y, Aozasa K et al, 2005, Humanized antiinterleukin- 6 receptor antibody treatment of multicentric Castleman disease. Blood 106:2627–2632
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Dieval C, Bonnet F, Mauclere S et al, 2007, Multicentric Castleman disease: Use of HHV8 viral load monitoring and positron emission tomography during follow-up. Leuk Lymphoma 48(9):1881–1883
Nakamura Y, Tokuyama O, Muso A et al, 2002, Asymptomatic pelvic Castleman disease in an infertile woman: case report. Arch Gynecol Obstet 269:156–158
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 375
EP 381
DI 10.1007/s12253-008-9133-x
PG 7
ER
PT J
AU Varkonyi, J
Bajzik, E
Fazakas,
Sipka, S
Karadi, I
AF Varkonyi, Judit
Bajzik, Edina
Fazakas, Adam
Sipka, Sandor
Karadi, Istvan
TI Short or Long Survival in Multiple Myeloma. A Simple Method for Determining the Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prognostic factors; Multiple myeloma; AMWBC score
ID Prognostic factors; Multiple myeloma; AMWBC score
AB Finding prognostic factors inmultiple myeloma is a real challenge. Several attempts might be found in the literature for that purpose but the results are not satisfactory. Therefore, in the current retorpective study authors analyzed the potential prognostic value of some laboratory data in 104 patients with multiple myeloma. They found the albumin and M-component ratio being lower than 1 and the initial WBC<4,5×109/l correlated strongly with poor prognosis. In addition the low albumin level was not related to albuminuria and that the low WBC was not linked to bone marrow infiltration rate or to antineutrophil antibody formation. On the basis of their experiences authors created an AMWBC score containing A/M and WBC at diagnosis found to be in good correlation to prognosis. Further studies involving more patients are needed to verify the real prognostic value of AMWBC score in multiple myeloma treated with new targeted therapies.
C1 [Varkonyi, Judit] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Bajzik, Edina] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Fazakas, Adam] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Sipka, Sandor] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
[Karadi, Istvan] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
RP Varkonyi, J (reprint author), Semmelweis University, 3rd Department of Internal Medicine, 1125 Budapest, Hungary.
EM varkjud@kut.sote.hu
CR Attal M, Harorusseau JL, Stoppa AM et al, 1996, A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. NEJM 335:9–7
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Kyle RA, GertzMA,Witzig TE et al, 2003, Review of 1,027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 78:21–33
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Anagnostopoulos A, Zervas K, Zomas A et al, 2003, The international prognostic index, IPI, is predictive for survival in refractory or relapsed myeloma patients treated with thalidomide– based regimens. Blood 937A:3492
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 383
EP 387
DI 10.1007/s12253-008-9134-9
PG 5
ER
PT J
AU Syamala, SV
Syamala, V
Sreedharan, H
Raveendran, BP
Kuttan, R
Ankathil, R
AF Syamala, S Volga
Syamala, Vani
Sreedharan, Hariharan
Raveendran, B Praveenkumar
Kuttan, Ratheesan
Ankathil, Ravindran
TI Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) Polymorphisms in Familial and Sporadic Breast Cancer Predisposition and Survival: An Indian Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Familial breast cancer; Low penetrance genes; Single nucleotide polymorphisms; Survival; XRCC1; XPD
ID Familial breast cancer; Low penetrance genes; Single nucleotide polymorphisms; Survival; XRCC1; XPD
AB The etiology of a significant proportion of familial breast cancers is still poorly understood, with known high penetrance gene mutations accounting for only a small proportion of the cases. The increased risk of breast cancer for the majority of women with a family history likely reflects shared minor low penetrant genetic factors. In the present case-control study undertaken to examine the influence of DNA damage repair gene polymorphisms in familial and sporadic breast cancer susceptibility, 219 Sporadic and 140 familial breast cancer patients and 367 controls were genotyped using PCRRFLP. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Variant genotypes XRCC1 Arg/Gln or Gln/Gln and XPD Lys/Gln or Gln/Gln increased both familial and sporadic breast cancer susceptibility. However, when the intra group risk was compared, the risk due to the XPD polymorphic genotypes Lys/Gln or Gln/Gln was significantly lower among familial breast cancer patients compared to sporadic breast cancer patients [OR=0.61; 95%CI=0.39–0.94; p value=0.024) whereas the risk implied by XRCC1 variant genotype was not significantly different between the familial and nonfamilial groups of breast cancer patients [OR=0.97; 95%CI=0.63–1.49; p value=0.882]. Both these variant genotypes were not associated with the disease characteristics or survival of either familial or sporadic breast cancer patients. This study represents an addition to previous published work on GSTs from the same study population and substantiates the hypothesis that the impact of the low penetrance gene polymorphisms differ by family history of the disease.
C1 [Syamala, S Volga] Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, Kerala, India.
[Syamala, Vani] Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, Kerala, India.
[Sreedharan, Hariharan] Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, Kerala, India.
[Raveendran, B Praveenkumar] Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, Kerala, India.
[Kuttan, Ratheesan] Regional Cancer Centre, Division of Radiation Oncology, 695011 Thiruvananthapuram, Kerala, India.
[Ankathil, Ravindran] Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, Kerala, India.
RP Ankathil, R (reprint author), Regional Cancer Centre, Division of Cancer Research, 695 011 Trivandrum, India.
EM rankathil@gmail.com
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Syamala VS, Sreeja L, Syamala V et al., 2008, Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Fam Cancer 7:213–220
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 389
EP 397
DI 10.1007/s12253-008-9135-8
PG 9
ER
PT J
AU Koornstra, JJ
de Jong, S
Boersma-van Eck, W
Zwart, Ny
Hollema, H
de Vries, GEE
Kleibeuker, HJ
AF Koornstra, J Jan
de Jong, Steven
Boersma-van Eck, Wietske
Zwart, Nynke
Hollema, Harry
de Vries, G E Elisabeth
Kleibeuker, H Jan
TI Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Colorectal cancer; Counterattack; Fas ligand; HNPCC; Lynch syndrome
ID Apoptosis; Colorectal cancer; Counterattack; Fas ligand; HNPCC; Lynch syndrome
AB Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and number of TILs in colorectal neoplasms from Lynch syndrome patients (50 adenomas, 20 carcinomas) compared with sporadic cases (69 adenomas, 52 carcinomas). FasL expression was observed in 94% of Lynch syndrome adenomas and in all carcinomas. FasL expression patterns and apoptotic indices were similar in Lynch syndrome-associated neoplasms and sporadic cases. The number of TILs was higher in Lynch syndrome neoplasms than in sporadic cases. There were no correlations between FasL expression and tumour cell apoptosis or number of TILs in Lynch syndrome-associated neoplasms. So, FasL expression is an early event in Lynch syndrome and sporadic colorectal carcinogenesis, but not related to TIL number. Taken together, our data do not support a role for the Fas counterattack in colorectal carcinogenesis in Lynch syndrome.
C1 [Koornstra, J Jan] University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, 9700 Groningen, RB, The Netherlands.
[de Jong, Steven] University of Groningen, University Medical Center Groningen, Department of Medical OncologyGroningen, RB, The Netherlands.
[Boersma-van Eck, Wietske] University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, 9700 Groningen, RB, The Netherlands.
[Zwart, Nynke] University of Groningen, University Medical Center Groningen, Department of Medical OncologyGroningen, RB, The Netherlands.
[Hollema, Harry] University of Groningen, University Medical Center Groningen, Department of PathologyGroningen, RB, The Netherlands.
[de Vries, G E Elisabeth] University of Groningen, University Medical Center Groningen, Department of Medical OncologyGroningen, RB, The Netherlands.
[Kleibeuker, H Jan] University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, 9700 Groningen, RB, The Netherlands.
RP Koornstra, JJ (reprint author), University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, 9700 Groningen, The Netherlands.
EM j.j.koornstra@int.umcg.nl
CR Hendriks YM, de Jong AE, Morreau H et al, 2006, Diagnostic approach and management of Lynch syndrome, hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA Cancer J Clin 56:213–225
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Rijcken FE, Hollema H, Kleibeuker JH, 2002, Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation. Gut 50:382–386
Koornstra JJ, de Jong S, Hollema H et al, 2003, Changes in apoptosis during the development of colorectal cancer: a systematic review of the literature. Crit Rev Oncol Hematol 45:37–53
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Houston AM, Michael-Robinson JM, Walsh MD et al, 2008, The “Fas counterattack” is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability. Hum Pathol 39:243–250
Michael-Robinson JM, Biemer-Huttmann A, Purdie DM et al, 2001, Tumour infiltrating lymphocytes and apoptosis are independent features in colorectal cancer stratified according to microsatellite instability status. Gut 48:360–366
Jackson PA, Green MA, Marks CG et al, 1996, Lymphocyte subset infiltration patterns and HLA antigen status in colorectal carcinomas and adenomas. Gut 38:85–89
Rubio CA, Jacobsson B, Castanos-Velez E, 1999, Cytotoxic intraepithelial lymphocytes in colorectal polyps and carcinomas. Anticancer Res 19(4B):3221–3227
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Walker JA, Quirke P, 2001, Viewing apoptosis through a TUNEL. J Pathol 195:275–276
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Ryan AE, Shanahan F, O’Connell J et al, 2005, Addressing the “Fas counterattack” controversy: blocking fas ligand expression suppresses tumor immune evasion of colon cancer in vivo. Cancer Res 65:9817–9823
Favre-Felix N, Fromentin A, Hammann A et al, 2000, Cutting edge: the tumor counterattack hypothesis revisited: colon cancer cells do not induce T cell apoptosis via the Fas, CD95, APO-1, pathway. J Immunol 5023–5027
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Jekle A, Obst R, Lang F et al, 2000, CD95/CD95 ligand-mediated counterattack does not block T cell cytotoxicity. Biochem Biophys Res Commun 272:395–399
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 399
EP 406
DI 10.1007/s12253-008-9136-7
PG 8
ER
PT J
AU Berstein, ML
Pozharisski, MK
Imyanitov, NE
Maximova, AN
Kovalevskij, YA
AF Berstein, M Lev
Pozharisski, M Kazimir
Imyanitov, N Evgeny
Maximova, A Natalya
Kovalevskij, Yu Anatoly
TI Aromatase, CYP1B1 and Fatty Acid Synthase Expression in Breast Tumors of BRCA1 Mutation Carriers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; BRCA1; Hormonal-metabolic factors; Aromatase; Catechol estrogens; Lipogenesis
ID Breast cancer; BRCA1; Hormonal-metabolic factors; Aromatase; Catechol estrogens; Lipogenesis
AB Numerous experimental evidence suggest that BRCA1-associated breast carcinomas may have distinct endocrine and metabolic features, however these peculiarities are poorly evaluated in clinical settings. Here we comparatively analyzed for the first time aromatase, estrogen 4-hydroxylase (CYP1B1) and fatty acid synthase immunohistochemical expression in breast tumors obtained from 12 BRCA1 mutations carriers and 22 non-carriers. Aromatase expression was higher in mutation carriers than in sporadic cases (p=0.04), which confirms the earlier results obtained in cell lines with down-regulated wild-type BRCA1 and corroborates the usage of aromatase inhibitors in such patients. No differences between study groups were found in the expression of CYP1B1 and fatty acid synthase, which does not, however, mitigate the need of further search for manifestations of the excessive genotoxic effects of estrogens and for increased lipogenesis in BRCA1 mutations carriers.
C1 [Berstein, M Lev] NN Petrov Institute of Oncology, Pesochny, 197758 Saint-Petersburg, Russian Federation.
[Pozharisski, M Kazimir] Scientific Center of Radiology and Surgical TechnologiesSaint-Petersburg, Russian Federation.
[Imyanitov, N Evgeny] NN Petrov Institute of Oncology, Pesochny, 197758 Saint-Petersburg, Russian Federation.
[Maximova, A Natalya] Scientific Center of Radiology and Surgical TechnologiesSaint-Petersburg, Russian Federation.
[Kovalevskij, Yu Anatoly] NN Petrov Institute of Oncology, Pesochny, 197758 Saint-Petersburg, Russian Federation.
RP Berstein, ML (reprint author), NN Petrov Institute of Oncology, 197758 Saint-Petersburg, Russian Federation.
EM levmb@endocrin.spb.ru
CR Welcsh PL, Owens KN, King MC, 2000, Insights into the functions of BRCA1 and BRCA2. Trends Genet 16:69–74
Eeles R, Kadouri L, 1999, BRCA1/2 carriers and endocrine risk modifiers. Endocr Relat Cancer 6:521–528
Hilakivi-Clarke L, 2000, Estrogens, BRCA1, and breast cancer. Cancer Res 60:4993–5001
Rosen EM, Fan S, Isaacs C, 2005, BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocr Relat Cancer 12(3):533–548
Hu Y, Ghosh S, Amleh A, Yue W, Lu Y, Katz A et al, 2005, Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression. Oncogene 24(56):8343–8348
Lu M, Chen D, Lin Z, Reierstad S, Trauernicht AM, Boyer TG et al, 2006, BRCA1 negatively regulates the cancer-associated aromatase promoters I.3 and II in breast adipose fibroblasts and malignant epithelial cells. J Clin Endocrinol Metab 91(11):4514–4519
Foulkes WD, Metcalfe K, Sun P, Hanna WM, Lynch HT, Ghadirian P et al, 2004, Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological grade. Clin Cancer Res 10(6):2029–2034
Hosey AM, Gorski JJ, Murray MM, Quinn JE, Chung WY, Stewart GE et al, 2007, Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. J Natl Cancer Inst 99(22):1683–1694
Bar Sade-Bruchim RB, Khalil T, Quenneville L, Foulkes W, Chong G, Aloyz RS, 2007, Determining the effect of estrogen metabolites on BRCA1-allelic imbalance in normal breast cells heterozygous for BRCA1 mutations. Proceedings of American Assoc. Cancer Res Annual Meeting, Los Angeles, CA, USA, Abstr 3475)
Cao L, Xu X, Cao LL, Wang RH, Coumoul X, Kim SS et al, 2007, Absence of full-length Brca1 sensitizes mice to oxidative stress and carcinogenesis. Carcinogenesis 28(7):1401–1407
Berstein LM, 2008, Endocrinology of wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol 4, 1):23–39
Shukla V, Coumoul X, Cao L, Wang RH, Xiao C, Xu X et al, 2006, Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members. Cancer Res 66(14):7151–7157
Moreau K, Dizin E, Ray H, Luquain C, Lefai E, Foufelle F et al, 2006, BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. J Biol Chem 281(6):3172–3181
Sokolenko AP, Mitiushkina NV, Buslov KG, Bit-Sava EM, Iyevleva AG, Chekmariova EV et al, 2006, High frequency of BRCA1 5382insC mutation in Russian breast cancer patients. Eur J Cancer 42(10):1380–1384
Adlercreutz H, Gorbach SL, Goldin BR, Woods MN, Dwyer JT, Hamalainen E, 1994, Estrogen metabolism and excretion in Oriental and Caucasian women. J Natl Cancer Inst 86(14):1076–1082
Cavalieri E, Chakravarti D, Guttenplan J, Hart E, Ingle J, Jankowiak R et al, 2006, Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta 1766(1):63–78
Menendez JA, Lupu R, 2007, Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7, 10):763–777
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Sasano H, Anderson TJ, Silverberg SG, Santen RJ, Conway M, Edwards DP et al, 2005, The validation of new aromatase monoclonal antibodies for immunohistochemistry—a correlation with biochemical activities in 46 cases of breast cancer. J Steroid Biochem Mol Biol 95(1–5):35–39
Marchetti P, Di Rocco CZ, Ricevuto E, Bisegna R, Cianci G, Calista F et al, 2004, Reducing breast cancer incidence in familial breast cancer: overlooking the present panorama. Ann Oncol 15(Suppl 1):I27–I34
Noruzinia M, Coupier I, Pujol P, 2005, Is BRCA1/BRCA2- related breast carcinogenesis estrogen dependent? Cancer 104, 8):1567–1574
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 407
EP 409
DI 10.1007/s12253-008-9137-6
PG 3
ER
PT J
AU Wu, Y
Liu, XM
Wang, XJ
Zhang, Y
Liang, XQ
Cao, EH
AF Wu, Yan
Liu, Xiao-Min
Wang, Xiao-Juan
Zhang, Yang
Liang, Xiao-Qiu
Cao, En-Hua
TI PIG11 is Involved in Hepatocellular Carcinogenesis and Its Over-expression Promotes Hepg2 Cell Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PIG11; HCC; Apoptosis; Tumour suppressor gene
ID PIG11; HCC; Apoptosis; Tumour suppressor gene
AB PIG11 (p53-induced gene 11) is a p53 target gene and candidate tumour suppressor gene. In this study, the expression of PIG11 protein was detected in human hepatocellular carcinoma (HCC) and normal liver tissues with an immunohistochemical method. Compared with expression in human normal liver tissues, the expression of PIG11 protein was significantly down-regulated in human HCC tissues. In addition, a recombinant pLXSNPIG11 retroviral vector was constructed and transfected into HepG2 cells (human hepatocellular carcinoma cell line) and the role of PIG11 in apoptosis was analyzed. The percentage (18.60%) of apoptotic cells transfected with pLXSN-PIG11 was higher than that in cells transfected with pLXSN only (6.03%) or the vehicle control (3.81%) (P<0.01). DNA gel electrophoresis showed a clear DNA ladder in pLXSN-PIG11-infected HepG2 cells. Our results suggested that the PIG11 gene is involved in carcinogenesis and development of hepatocarcinoma. Therefore, PIG11 is considered to be a new candidate liver tumour suppressor gene, and may play an important role in tumour suppression through promotion of cell apoptosis.
C1 [Wu, Yan] University of South China, Department of Pathology, 421001 Hengyang, Hunan, China.
[Liu, Xiao-Min] University of South China, Department of Pathology, 421001 Hengyang, Hunan, China.
[Wang, Xiao-Juan] University of South China, Department of Pathology, 421001 Hengyang, Hunan, China.
[Zhang, Yang] University of South China, Department of Pathology, 421001 Hengyang, Hunan, China.
[Liang, Xiao-Qiu] University of South China, Department of Pathology, 421001 Hengyang, Hunan, China.
[Cao, En-Hua] Chinese Academy of Science, Institute of Biophysics, 15 Datun Road, Chaoyang District, 100101 Beijing, China.
RP Liang, XQ (reprint author), University of South China, Department of Pathology, 421001 Hengyang, China.
EM liangxiaoqiu505@hotmail.com
CR Polyak K, Xia Y, Zweier JL et al, 1997, A model for p53-induced apoptosis. Nature 389:300–305
Zhu J, Jiang J, Zhou W et al, 1999, Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activity. Oncogene 18:2149–2155
Woo SH, Park IC, Park MJ et al, 2002, Arsenic trioxide induces apoptosis through a reactive oxygen spcies-dependent pathway and loss of mitochondrial menbrane potential in Hele cells. Int J Oncol 21:57–63
Ramachandran C, Rodriguez S, Ramachandran R et al, 2005, Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res 25(5):3293–3302
Chiba T, Yokosuka O, Fukai K et al, 2004, Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells. Oncology 66(6):481– 491
Liang XQ, Cao EH, Zhang Y et al, 2003, p53-induced gene 11, PIG11, involved in arsenic trioxide induced apoptosis in human gastric cancer MGC-803 cells. Oncology Reports 10(5):1265– 1269
Xiong X, Li H, Cao EH, 2007, PIG11 protein binds to DNA in sequence-independent manner in vitro. BBRC 358:29–34
Liang XQ, Cao EH, Zhang Y et al, 2004, A p53 target gene, PIG11, contributes to chemosensitivity of cells to arsenic trioxide. FEBS Letters 569(1–3):94–98
Ricketts SL, Carter JC, Coleman WB, 2003, Identification of three 11p11.2 candidate liver tumor suppressors through analysis of known human genes. Mol Carcinog 36(2):90–99
Xu L, Hui AY, Albanis E et al, 2005, Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 54:142–151
Chiba T, Yokosuka O, Fukai K et al, 2004, Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells. Oncology 66:481–491
Song H, Xu Y, 2007, Gain of function of p53 cancer mutants in disrupting critical DNA damage response pathways. Cell Cycle 6, 13):1570–1573
Leder A, McMenamin J, Zhou F et al, 2008, Genome-wide SNP analysis of Tg.AC transgenic mice reveals an oncogenic collaboration between v-Ha-ras and Ink4a, which is absent in p53 deficiency. Oncogene 27(17):2456–2465
Feng W, Xiao J, Zhang Z et al, 2007, Senescence and apoptosis in carcinogenesis of cervical squamous carcinoma. Mod Pathol 20, 9):961–966
Liu L, Qing S, Chen H et al, 2000, An experimental study on arsenic trioxide-selectively induced human hepatocarcinoma cell lines apoptosis and its related genes. Zhonghua Gan Zang Bing Za Zhi 8(6):367–371, Chinese)
Rivera A, Maxwell SA, 2005, The p53-induced gene-6, proline oxidase, mediates apoptosis through a calcineurin-dependent pathway. J Biol Chem 280:29346–29354
Ding WX, Shen HM, Ong CN et al, 2000, Critical role of reactive oxygen species and mitochondrial permeability transition in microcystin-induced rapid apoptosis in rat hepatocytes. Hepatology 32(3):547–555
Touyz RM, 2005, Reactive oxygen species as mediators of calcium signaling by angiotensin II:implications in vascular physiology and pathophysiology. Antioxid Redox Signal 7(9–10):1302– 1314
KimHJ, Chakravarti N,Oridate N et al, 2006, N-(4-Hydroxyphenyl, retinamide-induced apoptosis triggered by reactive oxygen species is mediated by activation of MAPKs in head and neck squamous carcinoma cells. Oncogene 25(19):2785–2794
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 411
EP 416
DI 10.1007/s12253-008-9138-5
PG 6
ER
PT J
AU Demir, R
Naschberger, L
Demir, I
Melling, N
Dimmler, A
Papadopoulus, Th
Sturzl, M
Klein, P
Hohenberger, W
AF Demir, Resit
Naschberger, Lisa
Demir, Ilknur
Melling, Nathaniel
Dimmler, Arno
Papadopoulus, Thomas
Sturzl, Michael
Klein, Peter
Hohenberger, Werner
TI Hypoxia Generates a More Invasive Phenotype of Tumour Cells: An In Vivo Experimental Setup Based on the Chorioallantoic Membrane
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chorioallantoic membrane; Hypoxia; Tumour invasion; Tumor progression
ID Chorioallantoic membrane; Hypoxia; Tumour invasion; Tumor progression
AB Of all processes involved in carcinogenesis, local invasion and the formation of metastases are the clinically most relevant but the scientifically least well understood at their molecular level. Recent experimental progress has identified that tumour hypoxia not only induces tumour angiogenesis, but also modulates the expression of several genes that have been implicated in tumour invasion and metastasis. Here we developed an in vivo model to understand a number of molecular pathways and cellular mechanisms for tumour invasion in hypoxia. For this purpose fertilized chicken eggs were incubated for 10 days in normoxic conditions. Subsequently colon carcinoma cells (SW-480) were placed on the chorioallantoic membrane. During the following 6 days the eggs were incubated either in normoxic conditions or in stepwise decreasing hypoxic conditions. SW-480 colon carcinoma cells did not invade the epithelial layer in normoxic conditions. In contrast an invasion through the epithelial layer in to the mesoderm was already seen after 3 days when incubated in hypoxic conditions. The chorioallantoic membrane assay described in this paper allows investigating tumour invasion and its cellular mechanisms under defined hypoxic conditions.
C1 [Demir, Resit] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
[Naschberger, Lisa] University of Erlangen, Department of Experimental SurgeryErlangen, Germany.
[Demir, Ilknur] University of Erlangen, Department of BiologyErlangen, Germany.
[Melling, Nathaniel] Albertinen-Krankenhaus, Department of SurgeryHamburg, Germany.
[Dimmler, Arno] St. Vincentius-Kliniken, Department of PathologyKarlsruhe, Germany.
[Papadopoulus, Thomas] Vivantes Humboldt Klinikum, Department of PathologyBerlin, Germany.
[Sturzl, Michael] University of Erlangen, Department of Experimental SurgeryErlangen, Germany.
[Klein, Peter] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
[Hohenberger, Werner] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
RP Demir, R (reprint author), University of Erlangen, Department of Surgery, D-91054 Erlangen, Germany.
EM resit.demir@uk-erlangen.de
CR Hart IR, Saini A, 1992, Biology of tumour metastasis. Lancet 339:1453–1457
Woodhouse EC, Chuaqui RF, Liotta LA, 1997, General mechanisms of metastasis. Cancer 80:1529–1537
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Kirchner T, Brabletz T, 2000, Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence. Analogies with embryonic gastrulation. Am J Pathol 157:1113–1121
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Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC, Samulski TV, Prosnitz LR, Dewhirst MW, 1996, Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res 56:5347–5350
Sullivan R, Graham CH, 2007, Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev 26:319–331
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Demir R, Hoper J, 1997, Effect of beta-interferon on vascular density, mitochondrial metabolism and alkaline phosphatase in normoxia and hypoxia. Adv Exp Med Biol 428:439– 447
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 417
EP 422
DI 10.1007/s12253-008-9140-y
PG 6
ER
PT J
AU Sughayer, AM
Zakarneh, L
Abu-Shakra, R
AF Sughayer, A Maher
Zakarneh, Lama
Abu-Shakra, Raffat
TI Collision Metastasis of Breast and Ovarian Adenocarcinoma in Axillary Lymph Nodes: A Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Collision metastasis
ID Collision metastasis
AB Despite their accepted clinical and genetic association, the incidence of synchronous breast and ovarian carcinoma is rare. Moreover, collision metastasis from both breast and ovarian carcinomas to the same lymph node, to our knowledge has never been reported. Review of the literature revealed eleven cases of metastatic malignant tumors colliding in the same lymph node, none of which had both ovarian and breast carcinoma. Our case was that of a 63 year old woman presenting with a breast lump that was diagnosed as infiltrating ductal carcinoma after a needle biopsy. One month later the patient was found to have malignant ascites, omental carcinomatosis and an ovarian mass. Histology and immunohistochemistry revealed high grade serous papillary adenocarcinoma. When surgery was done to treat the breast tumor some of the axillary lymph nodes revealed metastases from the breast primary, others metastases from the ovarian primary and one had both tumors in a collision phenomenon. Immunohistochemistry was used to confirm this finding.
C1 [Sughayer, A Maher] King Hussein Cancer CenterAmman, Jordan.
[Zakarneh, Lama] King Hussein Cancer CenterAmman, Jordan.
[Abu-Shakra, Raffat] Ministry of National Guard-Health Affairs, King Abdulaziz Medical City, King Abdullah International Medical Research CentreJeddah, Saudi Arabia.
RP Sughayer, AM (reprint author), King Hussein Cancer Center, Amman, Jordan.
EM msughayer@khcc.jo
CR Wade ZK, Shippey JE, Hamon GA et al, 2004, Collision metastasis of prostatic and colonic adenocarcinoma. Arch Pathol Lab Med 128(3):318–320 Mar
Mourra N, Parc Y, McNamara D et al, 2005, Lymph node metastases of prostatic adenocarcinoma in the mesorectum in patients with adenocarcinoma or villous tumor of the rectum with collision phenomenon in a single lymph node: report of five cases. Dis Colon Rectum. 48(2):384–389 Feb
Morgen AD, 1969, Carcinomas of rectum and prostatemetastasizing to the same lymph nodes. J Pathol 97:143–145
Ergen A, Balbay MD, Irwin M, Torno R, 1995, Collision metastasis of bladder and prostate carcinoma to a single pelvic lymph node. Int Urol Nephrol 27(6):743–745
Gohji K, Nomi M, Kizaki T et al, 1997, “Collision phenomenon” of prostate and bladder cancers in lymph node metastases. Int J Urol 4(2):222–224 Mar
Overstreet K, Haghighi P, 2001, Urothelial and prostate carcinoma metastasizing to the same lymph node: a case report and review of the literature. Arch Pathol Lab Med 125(10):1354–1357 Oct
Terada T, Satoh Y, Aoki N et al, 1993, The coexistence of cancer cells of different origin within the same lymph nodes. Surg Radiol Anat 15:119–123
Allal AS, Weintraub J, Remadi S, Abele R, 1996, Concurrent interfollicular Hodgkin’s disease and metastatic breast carcinoma in lymph nodes. Pathol Int 46(10):787–790 Oct
Pastolero GC, Coire CI, Asa SL, 1996, Concurrent medullary and papillary carcinomas of thyroid with lymph node metastases. A collision phenomenon. Am J Surg Pathol 20(2):245–250 Feb
Carbone A, Volpe R, 1983, Kaposi’s sarcoma in lymph nodes concurrent with Hodgkin’s disease. Am J Clin Pathol 80(2):228– 230 Aug
Miki Y, Swensen J, Shattuck-Eidens D et al, 1994, A strong candidate for breast and ovarian cancer susceptibility gene BRCA-1. Science 266:66–71
Wooster R, Neuhausen SL, Mangion J et al, 1994, Localization of a breast cancer susceptibility gene, BRCA-2, to chromosome 13q 12–13. Science 265:2088–2090
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 423
EP 427
DI 10.1007/s12253-008-9141-x
PG 5
ER
PT J
AU Ohara, T
Kawashiri, Sh
Tanaka, A
Noguchi, N
Kitahara, H
Okamune, A
Kato, K
Hase, T
Nakaya, H
Yoshizawa, K
AF Ohara, Teruhisa
Kawashiri, Shuichi
Tanaka, Akira
Noguchi, Natsuyo
Kitahara, Hiroko
Okamune, Ayako
Kato, Koroku
Hase, Takashi
Nakaya, Hiromitsu
Yoshizawa, Kunio
TI Integrin Expression Levels Correlate with Invasion, Metastasis and Prognosis of Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Integrin; Oral squamous cell carcinoma; Invasion; Metastasis; Prognosis
ID Integrin; Oral squamous cell carcinoma; Invasion; Metastasis; Prognosis
AB The present study evaluated the relationship between alpha 3, alpha 6A, and beta 1 integrin expression in cancer cells at the invasive front of oral squamous cell carcinoma (OSCC) and survival rates, as well as the clinical and pathological characteristics. Sections of 100 specimens of primary OSCC were immunostained to assess alpha 3, alpha 6A, and beta 1 integrin expression in cancer cells at the invasive front. OSCC patients with higher expression levels of alpha 3, alpha 6A, and beta 1 integrin had significantly better prognosis than those with lower expression levels (median survival at low vs. high expression levels: alpha 3, 37.1 months vs. 55.7 months; alpha 6A, 38.3 months vs. 47.9 months; and beta 1, 26.1 months vs. 46.1 months) (P<0.05). In addition, beta 1 integrin expression showed the highest correlation with clinical and pathological characteristics. This study concludes that alpha 3, alpha 6A, and beta 1 integrin expression in cancer cells at the invasive front are related to the mode of invasion and prognosis in OSCC.
C1 [Ohara, Teruhisa] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Kawashiri, Shuichi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Tanaka, Akira] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Noguchi, Natsuyo] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Kitahara, Hiroko] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Okamune, Ayako] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Kato, Koroku] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
[Hase, Takashi] Noto Hospital, Department of Oral Surgery, 926-8610 Nanao, Ishikawa, Japan.
[Nakaya, Hiromitsu] Municipal Tsuruga Hospital, Department of Oral Surgery, 914-8502 Tsuruga, Fukui, Japan.
[Yoshizawa, Kunio] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8640 Kanazawa, Ishikawa, Japan.
RP Kawashiri, Sh (reprint author), Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 920-8640 Kanazawa, Japan.
EM skawa@med.kanazawa-u.ac.jp
CR Tamkun JW, DeSimone DW, Fonda D et al, 1986, Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 46:271–282
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Calderwood DA, 2004, Integrin activation. J Cell Sci 117:657–666
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Jim H, Varner J, 2004, Integrins: roles in cancer development and as treatment targets. Br J of Cancer 90:561–565
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Satake J, Suzuki M, Yokoyama J et al, 1995, Integrin distribution in head and neck cancer: association of the α6 subunit with cervical lymph node metastasis. Jpn J Head Neck Cancer 21:1–5
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 429
EP 436
DI 10.1007/s12253-008-9142-9
PG 8
ER
PT J
AU Laughlin, MK
Luo, D
Liu, Ch
Shaw, G
Warrington, HK
Qiu, J
Yachnis, TA
Harrison, KJ
AF Laughlin, M Katharine
Luo, Defang
Liu, Che
Shaw, Gerry
Warrington, H Kenneth
Qiu, Jingxin
Yachnis, T Anthony
Harrison, K Jeffrey
TI Hematopoietic- and Neurologic-Expressed Sequence 1 Expression in the Murine GL261 and High-Grade Human Gliomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GL261; Tumor; siRNA; Jupiter; AAV; Glioma
ID GL261; Tumor; siRNA; Jupiter; AAV; Glioma
AB The hematopoietic- and neurologic-expressed sequence 1 (Hn1) gene encodes a highly conserved protein that is expressed in developing and regenerating tissues. In this study, Hn1 expression was evaluated in human and murine malignant gliomas. Hn1 mRNA and protein were detected in the murine GL261 glioma cell line and in GL261 brain tumors in vivo. HN1 is also expressed in human U118MG and U87MG cell lines. Evaluation of human brain tumors using an anti-Hn1 polyclonal antibody detected strong immunoreactivity in high-grade (WHO III and IV) malignant gliomas. The rate of GL261 cell proliferation in vitro was unaltered by Hn1 depletion using an anti-Hn1 siRNA. However, tumors established from Hn1-depleted GL261 cells formed significantly smaller volumes than those established from control-treated cells. These data suggest a role for Hn1 in the biology of malignant brain tumors.
C1 [Laughlin, M Katharine] University of Florida, College of Medicine, Department of Pharmacology & Therapeutics, 1600 SW Archer Rd, 32610-0267 Gainesville, FL, USA.
[Luo, Defang] University of Florida, College of Medicine, Department of Pharmacology & Therapeutics, 1600 SW Archer Rd, 32610-0267 Gainesville, FL, USA.
[Liu, Che] University of Florida, College of Medicine, Department of Pharmacology & Therapeutics, 1600 SW Archer Rd, 32610-0267 Gainesville, FL, USA.
[Shaw, Gerry] University of Florida, College of Medicine, Department of Neuroscience, 32610-0267 Gainesville, FL, USA.
[Warrington, H Kenneth] University of Florida, College of Medicine, Department of Pediatrics, 32610-0267 Gainesville, FL, USA.
[Qiu, Jingxin] University of Florida, College of Medicine, Department of Pathology, 32610-0267 Gainesville, FL, USA.
[Yachnis, T Anthony] University of Florida, College of Medicine, Department of Pathology, 32610-0267 Gainesville, FL, USA.
[Harrison, K Jeffrey] University of Florida, College of Medicine, Department of Pharmacology & Therapeutics, 1600 SW Archer Rd, 32610-0267 Gainesville, FL, USA.
RP Harrison, KJ (reprint author), University of Florida, College of Medicine, Department of Pharmacology & Therapeutics, 32610-0267 Gainesville, USA.
EM jharriso@ufl.edu
CR Zujovic V, Luo D, Baker HV, Lopez MC, Miller KR, Streit WJ, Harrison JK, 2005, The facial motor nucleus transcriptional program in response to peripheral nerve injury identifies Hn1 as a regeneration-associated gene. J Neurosci Res 82:581–591
Goto T, Hisatomi O, Kotoura M, Tokunaga F, 2006, Induced expression of hematopoietic- and neurologic-expressed sequence 1 in retinal pigment epithelial cells during newt retina regeneration. Exp Eye Res 83:972–980
Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I, Smith D, Hartmann L, Fishman D, Berchuck A, Schmandt R, Whitaker R, Gershenson DM, Mills GB, Bast RC, Jr., 2004, Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 10:3291–3300
Tang W, Lai YH, Han XD, Wong PM, Peters LL, Chui DH, 1997, Murine Hn1 on chromosome 11 is expressed in hemopoietic and brain tissues. Mamm Genome 8:695–696
Zhou G, Wang J, Zhang Y, Zhong C, Ni J, Wang L, Guo J, Zhang K, Yu L, Zhao S, 2004, Cloning, expression and subcellular localization of HN1 and HN1L genes, as well as characterization of their orthologs, defining an evolutionarily conserved gene family. Gene 331:115–123
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Church GM, Gilbert W, 1984, Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995
Harris J, Ayyub C, Shaw G, 1991, A molecular dissection of the carboxyterminal tails of the major neurofilament subunits NF-M and NF-H. J Neurosci Res 30:47–62
McCarty DM, Monahan PE, Samulski RJ, 2001, Self-complementary recombinant adeno-associated virus, scAAV, vectors promote efficient transduction independently of DNA synthesis. Gene Ther 8:1248–1254
Zolotukhin S, Potter M, Zolotukhin I, Sakai Y, Loiler S, Fraites TJ, Jr., Chiodo VA, Phillipsberg T, Muzyczka N, Hauswirth WW, Flotte TR, Byrne BJ, Snyder RO, 2002, Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors. Methods 28:158–167
Harrison JK, Luo D, Streit WJ, 2003, In situ hybridization analysis of chemokines and chemokine receptors in the central nervous system. Methods 29:312–318
Qiu J, Ai L, Ramachandran C, Yao B, Gopalakrishnan S, Fields CR, Delmas AL, Dyer LM, Melnick SJ, Yachnis AT, Schwartz PH, Fine HA, Brown KD, Robertson KD, 2008, Invasion suppressor cystatin E/M, CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas. Lab Invest 88:910–925
Liu C, Luo D, Streit WJ, Harrison JK, 2008, CX3CL1 and CX3CR1 in the GL261 murine model of glioma: CX3CR1 deficiency does not impact tumor growth or infiltration of microglia and lymphocytes. J Neuroimmunol 198:98–105
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P, 2007, The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Pescarmona GP, Scalerandi M, Delsanto PP, Condat CA, 1999, Non-linear model of cancer growth and metastasis: a limiting nutrient as a major determinant of tumor shape and diffusion. Med Hypotheses 53:497–503
Seiki M, 2003, Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett 194:1–11
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 437
EP 444
DI 10.1007/s12253-008-9147-4
PG 8
ER
PT J
AU Papay, J
Sapi, Z
Egri, G
Gyulai, M
Szende, B
Losonczy, Gy
Timar, J
Moldvay, J
AF Papay, Judit
Sapi, Zoltan
Egri, Gabor
Gyulai, Marton
Szende, Bela
Losonczy, Gyorgy
Timar, Jozsef
Moldvay, Judit
TI Platinum-Based Chemotherapy in Lung Cancer Affects the Expression of Certain Biomarkers Including ERCC1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemotherapy; Immunohistochemistry; Lung cancer; Molecular biology; Neoadjuvant treatment
ID Chemotherapy; Immunohistochemistry; Lung cancer; Molecular biology; Neoadjuvant treatment
AB Chemotherapies are widely used in the treatment of lung cancer. However, little is known about their effect in the expression of different tissue markers. Seventeen lung cancer tissue blocks obtained by bronchoscopic biopsies together with their corresponding surgical biopsies after neoadjuvant chemotherapy were studied. They included 9 adenocarcinomas (ADC) and 8 squamous cell carcinomas (SCC). Immunohistochemistry was performed on formalinfixed, paraffin-embedded tissues to study the expression of Ki-67, p53, Bcl-2, Bax, Fas-ligand and ERCC1 (excision repair cross-complementation group 1). Out of 17 NSCLC 6 expressed proapoptotic markers and 4 expressed antiapoptotic markers, while in 7 cases the apoptotic markers did not show detectable changes after neoadjuvant chemotherapy. Six of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment. Eight bronchoscopic NSCLC tissues (6 SCC, 2 ADC) expressed ERCC1. All but one ADC became ERCC1 negative after neoadjuvant therapy. There was no newly expressed ERCC1 positive case in the surgical biopsy group. Platinum-based neoadjuvant chemotherapy had no effect on the apoptotic activity of 17 patients’ tumor specimen, however, 6 of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment, in 3 cases the level of Ki-67 became decreased, while 8 cases had no detectable change of proliferation activity. The results of the present study suggest that platinum-based chemotherapy probably induces a selection of tumor cells with more aggressive phenotype, and also affects the expression of tissue marker (ERCC1) that could have predictive value.
C1 [Papay, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Egri, Gabor] Bajcsy Hospital, Department of SurgeryBudapest, Hungary.
[Gyulai, Marton] County Hospital of PulmonologyTorokbalint, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Losonczy, Gyorgy] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c., H-1125 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Moldvay, Judit] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c., H-1125 Budapest, Hungary.
RP Moldvay, J (reprint author), Semmelweis University, Department of Pulmonology, H-1125 Budapest, Hungary.
EM drmoldvay@hotmail.com
CR U.S. Cancer Statistics Working Group. United States Cancer Statistics: 2002–2004 Incidence and Mortality Web-based Report Version. Atlanta, GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2007
Noble J, Ellis PM, Mackay JA et al, 2006, Second-line or subsequent systemic therapy for recurrent or progressive nonsmall cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 9:1042–58
Junker K, Langner K, Klinke F et al, 2001, Grading of tumor regression in non-small cell lung cancer: morphology and prognosis. Chest. 120(5):1584–91
Morero JL, Poleri C, Martin C et al, 2007, Influence of apoptosis and cell cycle regulator proteins on chemotherapy response and survival in stage IIIA/IIIB NSCLC patients. J Thorac Oncol. 4:293–8
Ikuta K, Takemura K, Kihara M et al, 2005, Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells. Oncol Rep. 13(6):1229–34
Filipits M, Pirker R, Dunant A et al, 2007, Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer: the International Adjuvant Lung Cancer Trial Biologic Program. J Clin Oncol. 25, 19):2735–40
Olaussen KA, Dunant A, Fouret P et al, 2006, DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355:983–91
Rigas JR, Kelly K, 2007, Current treatment paradigms for locally advanced non-small cell lung cancer. J Thorac Oncol. 2(Suppl 2): S77–85
Gilligan D, Nicolson M, Smith I et al, 2007, Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 369(9577):1929–37
de Marinis F, Tedesco B, Treggiari S et al, 2007, Role of induction chemotherapy in resectable N2 non-small cell lung cancer. J Thorac Oncol. 5(Suppl 5):S31–4
Abratt RP, Lee JS, Han JY et al, 2006, Phase II trial of gemcitabine-carboplatin-paclitaxel as neoadjuvant chemotherapy for operable non-small cell lung cancer. J Thorac Oncol. 2:135–40
Stinchcombe TE, Socinski MA, 2007, The role of induction therapy for resectable non-small cell lung cancer. Drugs. 67, 3):321–32
De Pauw R, van Meerbeeck JP, 2007, Neoadjuvant chemotherapy in the treatment of nonsmall-cell lung cancer. Curr Opin Oncol. 19, 2):92–7
Meert AP, Martin B, Verdebout JM et al, 2004, Correlation of different markers, p53, EGF-R, c-erbB-2, Ki-67, expression in the diagnostic biopsies and the corresponding resected tumors in nonsmall cell lung cancer. Lung Cancer. 44(3):295–301
Lang DS, Droemann D, Schultz H et al, 2007, A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy. Respir Res. 14;8:43
Fujii T, Toyooka S, Ichimura K et al, 2008, ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer. Lung Cancer 59, 3):377–84
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 445
EP 450
DI 10.1007/s12253-009-9155-z
PG 6
ER
PT J
AU Younes, AS
Csire, M
Kapusinszky, B
Szomor, K
Takacs, M
Berencsi, Gy
AF Younes, Ali Saleh
Csire, Marta
Kapusinszky, Beatrix
Szomor, Katalin
Takacs, Maria
Berencsi, Gyorgy
TI Heterogeneous Pathways of Maternal-fetal Transmission of Human Viruses (Review)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Syncytiotrophoblast; Fetal endothelium; Virus transcytosis; Maternal-fetal transport
ID Syncytiotrophoblast; Fetal endothelium; Virus transcytosis; Maternal-fetal transport
AB Several viruses can pass the maternal-fetal barrier, and cause diseases of the fetus or the newborn. Recently, however, it became obvious, that viruses may invade fetal cells and organs through different routes without acute consequences. Spermatozoa, seminal fluid and lymphocytes in the sperm may transfer viruses into the human zygotes. Viruses were shown to be integrated into human chromosomes and transferred into fetal tissues. The regular maternal-fetal transport of maternal cells has also been discovered. This transport might implicate that lymphotropic viruses can be released into the fetal organs following cellular invasion. It has been shown that many viruses may replicate in human trophoblasts and syncytiotrophoblast cells thus passing the barrier of the maternalfetal interface. The transport of viral immunocomplexes had also been suggested, and the possibility has been put forward that even anti-idiotypes mimicking viral epitopes might be transferred by natural mechanisms into the fetal plasma, in spite of the selective mechanisms of apical to basolateral transcytosis in syncytiotrophoblast and basolateral to apical transcytosis in fetal capillary endothelium. The mechanisms of maternal-fetal transcytosis seem to be different of those observed in differentiated cells and tissue cultures. Membrane fusion and lipid rafts of high cholesterol content are probably the main requirements of fetal transcytosis. The long term presence of viruses in fetal tissues and their interactions with the fetal immune system might result in post partum consequences as far as increased risk of the development of malignancies and chronic pathologic conditions are discussed.
C1 [Younes, Ali Saleh] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
[Csire, Marta] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
[Kapusinszky, Beatrix] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
[Szomor, Katalin] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
[Takacs, Maria] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
[Berencsi, Gyorgy] National Center for Epidemiology, Division of Virology, Gyali Street 2–6, 1097 Budapest, Hungary.
RP Berencsi, Gy (reprint author), National Center for Epidemiology, Division of Virology, 1097 Budapest, Hungary.
EM berencsi.gyorgy@oek.antsz.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 451
EP 465
DI 10.1007/s12253-009-9166-9
PG 15
ER
PT J
AU Kabukcuoglu, F
Kabukcuoglu, Y
Tanik, C
Sakiz, D
Karsidag, S
AF Kabukcuoglu, Fevziye
Kabukcuoglu, Yavuz
Tanik, Canan
Sakiz, Damlanur
Karsidag, Semra
TI Breast Carcinoma Metastasis in Recurrent Myxoid Liposarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Beta-catenin; Breast cancer; E-cadherin; Liposarcoma; Tumor to tumor metastasis
ID Beta-catenin; Breast cancer; E-cadherin; Liposarcoma; Tumor to tumor metastasis
AB Tumor to tumor metastasis is a rare, but well recognized entity, most commonly involving a carcinoma metastasis to a benign or low grade mesenchymal tumor. A case of breast carcinoma metastasis in a recurrent myxoid liposarcoma is presented in this study. A 52-year-old female patient with a history of breast carcinoma (70% invasive lobular carcinoma and 30% invasive ductal carcinoma) presented with a mass in the right lumbar region. The excised mass was diagnosed as myxoid liposarcoma. The tumor recurred twice and was reexcised. Microscopic examination of the second recurrence revealed multiple foci of breast carcinoma metastases in myxoid liposarcoma. Immunohistochemical study showed staining for CK19, GCDFP-15, estrogen and progesterone in metastases. Both breast carcinoma metastasis and myxoid liposarcoma were immunoreactive for E-cadherin and beta-catenin. To our knowledge, this is the first reported case of breast carcinoma metastasis in myxoid liposarcoma, and the first occurrence of metastasis in a liposarcoma.
C1 [Kabukcuoglu, Fevziye] Sisli Etfal Training and Research Hospital, Department of Pathology, M. Ismail Hakki Sk. No:10/1 Uskudar, 34672 Istanbul, Turkey.
[Kabukcuoglu, Yavuz] Taksim Training and Research Hospital, Department of Orthopedics and TraumatologyIstanbul, Turkey.
[Tanik, Canan] Sisli Etfal Training and Research Hospital, Department of Pathology, M. Ismail Hakki Sk. No:10/1 Uskudar, 34672 Istanbul, Turkey.
[Sakiz, Damlanur] Sisli Etfal Training and Research Hospital, Department of Pathology, M. Ismail Hakki Sk. No:10/1 Uskudar, 34672 Istanbul, Turkey.
[Karsidag, Semra] Sisli Etfal Training and Research Hospital, Department of Plastic Surgery and ReconstructionIstanbul, Turkey.
RP Kabukcuoglu, F (reprint author), Sisli Etfal Training and Research Hospital, Department of Pathology, 34672 Istanbul, Turkey.
EM fkabukcuoglu@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 467
EP 471
DI 10.1007/s12253-008-9121-1
PG 5
ER
PT J
AU Yuan, W
Chen, Z
Wu, Sh
Ge, J
Chang, Sh
Wang, X
Chen, J
Chen, Z
AF Yuan, Weijie
Chen, Zhikang
Wu, Shaobin
Ge, Jie
Chang, Shi
Wang, Xianwei
Chen, Jingxiang
Chen, Zihua
TI Expression of EphA2 and E-cadherin in Gastric Cancer: Correlated with Tumor Progression and Lymphogenous Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EphA2; E-cadherin; Gastric cancer; Immunohistochemistry
ID EphA2; E-cadherin; Gastric cancer; Immunohistochemistry
AB In this study, gastric cancer progression was correlated with the over-expression of erythropoietin-producing hepatocellular (Eph)A2 receptor and down-expression of epithelial cadherin (E-cadherin). Immunohistochemistry of EphA2 and E-cadherin were performed on these tumor samples from 165 primary lesions of gastric cancer. The results showed that expression of EphA2 was obviously increased in gastric cancer tissues (P<0.01), which was positively correlated with the depth of cancer invasion, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). Meanwhile, the expression of E-cadherin was significantly reduced (P<0.01), which was negatively correlated with the depth of cancer invasion, grade of tumor differentiation, TNM stage and lymph node metas tasis (P<0.05). The correlation between EphA2 and Ecadherin expression was negative (r=−0.198, P=0.011). In conclusion, either the over-expression of EphA2 or the down-expression of E-cadherin is correlated with cancer progression and lymphogenous metastasis in gastric cancer, suggesting that both of them may play an important role in tumor progression and metastasis.
C1 [Yuan, Weijie] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Chen, Zhikang] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Wu, Shaobin] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Ge, Jie] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Chang, Shi] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Wang, Xianwei] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Chen, Jingxiang] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
[Chen, Zihua] Central South University, Xiangya Hospital, Department of General Surgery, Xiangya Road, 410008 Changsha, Hunan Province, China.
RP Chen, Z (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
EM chenzihua1@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 473
EP 478
DI 10.1007/s12253-008-9132-y
PG 6
ER
PT J
AU Kiss, LA
Botos, E
AF Kiss, L Anna
Botos, Erzsebet
TI Ocadaic Acid Retains Caveolae in Multicaveolar Clusters
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveola; Alternative endocytosis; Caveosomes; Ocadaic acid
ID Caveola; Alternative endocytosis; Caveosomes; Ocadaic acid
AB Caveola-mediated endocytosis exists parallel to other forms of endocytosis. Being ligand-triggered, caveolar endocytosis provides a more selective and highly regulated way for uptake of specified substances. Internalized caveolae accumulate in intermediate organelles called caveosomes. It is still debated whether caveosomes are independent organelles or the downstream caveosomes interact with the classical endocytotic compartments. In our work caveola internalization was stimulated with a serine/threonine phosphatase (PP1 and PP2A) inhibitor (ocadaic acid—OA). To find out whether caveolar clusters are really independent organelles or they are still connected to the cell surface we used an electron dense surface marker, ruthenium red (Ru red). Since we were especially interested in the fate of caveolar clusters, the cells were treated with OA for longer time. Stimulating caveola-mediated endocytosis, OA treatment resulted in a significant increase in the number of caveolar cluster. Most of these clusters were found Ru red positive indicating that they were still conneted to the cell surface. Our double labeling experiments on ultrathin frozen sections clearly showed that in OA-treated cells caveolae are not transported to late endosomes instead they are accumulted in large multicaveolar clusters. We think that PP2A can be one of the key components to regulate the fusion of various endocytotic compartments and/or the trafficking along the microtubules.
C1 [Kiss, L Anna] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58, 1094 Budapest, Hungary.
[Botos, Erzsebet] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58, 1094 Budapest, Hungary.
RP Kiss, LA (reprint author), Semmelweis University, 1st Department of Anatomy, 1094 Budapest, Hungary.
EM KissA@ana2.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 479
EP 486
DI 10.1007/s12253-008-9139-4
PG 8
ER
PT J
AU Chen, Y
Lu, Y
Lu, Ch
Zhang, L
AF Chen, Yongshun
Lu, You
Lu, Changli
Zhang, Lei
TI Beclin-1 Expression is a Predictor of Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma and Correlated to Hypoxia-Inducible Factor (HIF)-1α Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Beclin-1; HIF-1α; Immunohistochemistry; Clinicopathological factors; Survival
ID Esophageal squamous cell carcinoma; Beclin-1; HIF-1α; Immunohistochemistry; Clinicopathological factors; Survival
AB In the present study, we examined the relationship between Beclin-1 expression and HIF-1α expression in esophageal squamous cell carcinoma(ESCC). There was a loss of Beclin-1 protein expression in 33% of ESCCs. Beclin-1 expression significantly correlated with depth of invasion, lymph node metastasis and clinical stage. Among the 54 patients, The survival rate of the Beclin-1-positive group was better than that of the Beclin-1-negative group. Twenty-five of the 54 (46%) tumor specimens showed high levels of HIF-1α immunoreactivity. Beclin-1 expression was associated with HIF-1α expression. The survival rate of patients with Beclin-1-positive and HIF-1α-low tumors was significantly higher than that of the other groups. These results suggest that Beclin-1 and HIF-1α expression are important determinants of survival in ESCCs.
C1 [Chen, Yongshun] Sichuan University, West China Hospital, Division of Thoracic Oncology, 37, Guoxue Lane, 610041 Chengdu, China.
[Lu, You] Sichuan University, West China Hospital, Division of Thoracic Oncology, 37, Guoxue Lane, 610041 Chengdu, China.
[Lu, Changli] Sichuan University, West China Hospital, Department of PathologyChengdu, China.
[Zhang, Lei] Sichuan University, West China Hospital, Department of NephrologyChengdu, China.
RP Lu, Y (reprint author), Sichuan University, West China Hospital, Division of Thoracic Oncology, 610041 Chengdu, China.
EM radyoulu@hotmail.com
CR Guimaraes CA, Linden R, 2004, Programmed cell death. Apoptosis and alternative deathstyles. Eur J Biochem 271:1638–1650
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 487
EP 493
DI 10.1007/s12253-008-9143-8
PG 7
ER
PT J
AU Zhang, ZB
Cai, L
Zheng, ShG
Xiong, Y
Dong, JH
AF Zhang, Zhi-Bo
Cai, Lei
Zheng, Shu-Guo
Xiong, Yan
Dong, Jia-Hong
TI Overexpression of Caveolin-1 in Hepatocellular Carcinoma with Metastasis and Worse Prognosis: Correlation with Vascular Endothelial Growth Factor, Microvessel Density and Unpaired Artery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveolin-1; Vascular endothelial growth factor; Angiogenesis; Metastasis; Prognosis; Hepatocellular carcinoma; Microvessel density; Unpaired artery
ID Caveolin-1; Vascular endothelial growth factor; Angiogenesis; Metastasis; Prognosis; Hepatocellular carcinoma; Microvessel density; Unpaired artery
AB Caveolin-1 is the major structural protein in caveolae, implicated in oncogenesis and angiogenesis. The connections between caveolin-1 and progression and angiogenesis of hepatocellular carcinoma (HCC) is still not clear. Thus we investigated the relationship of caveolin-1 expression, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), and unpaired artery (UA) with the clinicopathologic features of patients with HCC. Formalin-fixed, paraffin-embedded tissue sections of HCC from 75 patients who had undergone an initial hepatectomy were stained immunohistochemically with specific antibodies against caveolin-1, VEGF, CD34 and α-SMA. The levels of caveolin-1, VEGF, MVD and UA were correlated with the clinicopathologic variables, and tissue sections were also analyzed by dual-label immunofluorescence. We found that increased expression of caveolin-1 was associated with metastasis and with a worse prognosis of HCC. Caveolin-1 expression correlates positively with VEGF, MVD and UA. These results suggest that caveolin-1 may play an important role in the progression of HCC and angiogenesis.
C1 [Zhang, Zhi-Bo] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
[Cai, Lei] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
[Zheng, Shu-Guo] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
[Xiong, Yan] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
[Dong, Jia-Hong] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
RP Dong, JH (reprint author), Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400038 Chongqing, China.
EM Jhdong301@163.com
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Podar K, Shringarpure R, Tai YT, Simoncini M, Sattler M, Ishitsuka K, Richardson PG, Hideshima T, Chauhan D, Anderson KC, 2004, Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Cancer Res 64:7500–7506
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 495
EP 502
DI 10.1007/s12253-008-9144-7
PG 8
ER
PT J
AU Stojsic, Z
Brasanac, D
Stojiljkovic, M
Babic, D
Randjelovic, T
Terzic, T
AF Stojsic, Zorica
Brasanac, Dimitrije
Stojiljkovic, Miodrag
Babic, Darko
Randjelovic, Tomislav
Terzic, Tatjana
TI Composite Carcinoma of the Stomach Associated with Sarcoid-Like Granulomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Composite exocrine-endocrine carcinoma; Gastric carcinoma; Immunohistochemistry; Sarcoid-like granuloma; Stomach
ID Composite exocrine-endocrine carcinoma; Gastric carcinoma; Immunohistochemistry; Sarcoid-like granuloma; Stomach
AB Composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is a special tumor type composed of common adenocarcinoma and the neuroendocrine component comprising at least one-third of the whole tumor area. These tumors are rare in the stomach and mostly published as case reports. We describe a further case of a 36-year-old man being unique in that it was associated with extensive formation of sarcoid-like granulomas. Tumor consisted of, predominantly poorly differentiated, intestinal-type adenocarcinoma and poorly differentiated neuroendocrine, small cell carcinoma. The adenocarcinomatous and neuroendocrine areas were separated, but closely juxtaposed with focal areas showing gradual transition from one to another. Perigastric lymph node metastases corresponded either to neuroendocrine or adenocarcinomatous component. On immunohistochemistry, the exocrine part was positive for cytokeratin 7, whereas superficial well-differentiated parts showed positivity with cytokeratin 20 as well. The neuroendocrine component was negative with those two types of cytokeratin. Both adenocarcinomatous and neuroendocrine tumor portions showed carcinoembryonic antigen (CEA) immunoexpression. Neuroendocrine markers (chromogranin A, synaptophysin and neuron-specific enolase) were diffusely positive in the neuroendocrine component, and found only in the scattered cells within the neoplastic glands of the adenocarcinoma. Entire gastric mucosa and all perigastric lymph nodes were extensively affected by noncaseating, sarcoidlike granulomas. The absence of any clinical manifestations combined with the negative results of chest radiograph and laboratory test for the serum angiotensin converting enzyme argued against the possibility of systemic sarcoidosis.
C1 [Stojsic, Zorica] University of Belgrade, Faculty of Medicine, Institute for Pathology, Dr Subotica 1/II, 11000 Belgrade, Serbia, Serbia.
[Brasanac, Dimitrije] University of Belgrade, Faculty of Medicine, Institute for Pathology, Dr Subotica 1/II, 11000 Belgrade, Serbia, Serbia.
[Stojiljkovic, Miodrag] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia, Serbia.
[Babic, Darko] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia, Serbia.
[Randjelovic, Tomislav] Clinical Centre, Clinical Department of SurgeryBelgrade, Serbia, Serbia.
[Terzic, Tatjana] University of Belgrade, Faculty of Medicine, Institute for Pathology, Dr Subotica 1/II, 11000 Belgrade, Serbia, Serbia.
RP Stojsic, Z (reprint author), University of Belgrade, Faculty of Medicine, Institute for Pathology, 11000 Belgrade, Serbia.
EM zstojsic@med.bg.ac.yu
CR Volante M, Rindi G, Papotti M, 2006, The grey zone between pure, neuro, endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrineendocrine neoplasms. Virchows Arch 449:499–506
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Ooi A, Mai M, Ogino T et al, 1988, Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. Cancer 62:1096–1104
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Jiang SX, Mikami T, Umezawa A et al, 2006, Gastric large cell neuroendocrine carcinomas: a distinct clinicopathologic entity. Am J Surg Pathol 30:945–953
Fenoglio-Preiser C, Munoz N, Carneiro F et al, 2000, Gastric carcinoma. In: Hamilton SR, Aaltonen LA, eds, World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the Digestive System. IARC, Lyon, pp 37–68
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 503
EP 510
DI 10.1007/s12253-008-9145-6
PG 8
ER
PT J
AU Tsiambas, E
Manaios, L
Papanikolopoulos, C
Rigopoulos, ND
Tsounis, D
Karameris, A
Soultati, A
Koliopoulou, A
Kravvaritis, Ch
Sergentanis, Th
Patsouris, E
Dourakis, S
AF Tsiambas, Evangelos
Manaios, Loukas
Papanikolopoulos, Costas
Rigopoulos, N Dimitrios
Tsounis, Dimitrios
Karameris, Andreas
Soultati, Aspasia
Koliopoulou, Antigoni
Kravvaritis, Christos
Sergentanis, Theodoros
Patsouris, Efstratios
Dourakis, Spyridon
TI Chromogenic In Situ Hybridization Analysis of Epidermal Growth Factor Receptor Gene/Chromosome 7 Numerical Aberrations in Hepatocellular Carcinoma Based on Tissue Microarrays
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chromogenic in situ hybridization; Epidermal growth factor receptor; Hepatocellular carcinoma; Tissue microarrays
ID Chromogenic in situ hybridization; Epidermal growth factor receptor; Hepatocellular carcinoma; Tissue microarrays
AB Although Epidermal Growth Factor Receptor (EGFR) overexpression is observed frequently in hepatocellular carcinomas (HCC), specific gene deregulation mechanisms remain unknown. Our aim was to investigate the prognostic significance of the combined protein and gene/chromosome 7 numerical alterations. Using tissue microarray technology, thirty-five (n=35) paraffin embedded histologically confirmed HCCs were cored and reembedded in a paraffin block. Immunohistochemistry was performed for the determination of EGFR protein levels and evaluated by the performance of digital image analysis. Chromogenic in situ hybridization was also performed based on the use of EGFR gene and chromosome 7 centromeric probes, respectively. EGFR overexpression was observed in 26/35 (74.2%) cases and was correlated to the grade of the tumors and also to the history of the patients (p=0.013, p=0.036, respectively). Numerical alterations regarding gene and chromosome 7 were identified in 4/35 (11.4%) and 12/35 (43.2%) cases associated to the grade of the tumors (p=0.019, p=0.001, respectively) and to the survival rate of the patients (p=0.037, p=0.001, respectively). EGFR overall expression was also correlated to the gene copies (p=0.020). EGFR gene numerical alterations –although rare– and also chromosome 7 aneuploidy maybe affect prognosis in HCC patients. To our knowledge this is the first chromogenic in situ hybridization analysis based on tissue microarrays in hepatocellular carcinoma.
C1 [Tsiambas, Evangelos] 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of Pathology, Section of Molecular Pathology, Ag Paraskevi Attiki, Patriarchou Grigoriou E 17, 15341 Athens, Greece.
[Manaios, Loukas] Bioclinic, Dept of SurgeryAthens, Greece.
[Papanikolopoulos, Costas] 401 GA Hospital, Dept of Internal MedicineAthens, Greece.
[Rigopoulos, N Dimitrios] 401 GA Hospital, Dept of Internal MedicineAthens, Greece.
[Tsounis, Dimitrios] 251 AF Hospital, Dept of GastroenterologyAthens, Greece.
[Karameris, Andreas] 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of PathologyAthens, Greece.
[Soultati, Aspasia] University of Athens, Hippokration H, Medical School, Dept of GastroenterologyAthens, Greece.
[Koliopoulou, Antigoni] Evangelismos Hospital, Dept of Thoracic SurgeryAthens, Greece.
[Kravvaritis, Christos] 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of PathologyAthens, Greece.
[Sergentanis, Theodoros] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Dourakis, Spyridon] University of Athens, Hippokration H, Medical School, Dept of GastroenterologyAthens, Greece.
RP Tsiambas, E (reprint author), 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of Pathology, Section of Molecular Pathology, 15341 Athens, Greece.
EM tsiambasecyto@yahoo.gr
CR El Serag H, Davila JA, Petersen NJ, McGlynn KA, 2003, The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139:817–23
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Ramanathan RK, Belani CP, Singh DA, 2006, Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor, EGFR, tyrosine kinase 1 and 2, Her2/Neu, in patients, pts, with advanced biliary tree cancer, BTC, or hepatocellular cancer, HCC). A California Consortium, CCC-P, Trial. J Clin Oncol 24:401
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 511
EP 520
DI 10.1007/s12253-008-9146-5
PG 10
ER
PT J
AU Milinovic, D
Kalafatic, D
Babic, D
Oreskovic, BL
Grsic, LH
Oreskovic, S
AF Milinovic, Darko
Kalafatic, Drzislav
Babic, Damir
Oreskovic, Beketic Lidija
Grsic, Lovric Helena
Oreskovic, Slavko
TI Minimally Invasive Therapy of Cervical Intraepithelial Neoplasia for Fertility Preservation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CIN III; Conization; Fertility preservation
ID CIN III; Conization; Fertility preservation
AB The aim of this study was to determine the extension of cervical intraepithelial neoplasia grade III (CIN III) into endocervical canal and depth of endocervical crypts involvement by CIN with the regard to patients’ age and parity. Correlation between the area of CIN involvement and the extension into endocervical canal was estimated. A total of 218 cervical cone specimens with histologically proven CIN III were included in this study. Extension of CIN into the endocervical canal, depth of involved crypts and ectocervical area affected by CIN were histologically analyzed. The average endocervical crypt involvement was at 1.2 mm of depth. The excision of >4 mm (1.2 mm × 3S.D.) in depth removes >99% of CIN. With the cone length of 15 mm (nulliparous patients) and 18 mm (multiparous patients), no endocervical cone margins were affected with CIN. Since the cone length is the most important determining factor for fertility preservation, the measurement of cervical cone could be essential for future pregnancies.
C1 [Milinovic, Darko] General Hospital Gospic, Department of Obstetrics and GynecologyGospic, Croatia.
[Kalafatic, Drzislav] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and GynecologyZagreb, Croatia.
[Babic, Damir] University of Zagreb, School of Medicine, Department of PathologyZagreb, Croatia.
[Oreskovic, Beketic Lidija] University Hospital for Tumors, Department of OncologyZagreb, Croatia.
[Grsic, Lovric Helena] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and GynecologyZagreb, Croatia.
[Oreskovic, Slavko] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and GynecologyZagreb, Croatia.
RP Kalafatic, D (reprint author), University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, Zagreb, Croatia.
EM drzislav.kalafatic@zg.t-com.hr
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Ljubojevic N, Babic S, Audy-Jurkovic S, et al, 1998, Loop excision of the transformation zone, LETZ, as an outpatient method of management for women with cervical intraepithelial neoplasia: our experience. Coll Antropol 22:533–543
Cecchini S, Visioli CB, Zappa M, Ciatto S., 2002, Recurrence after treatment by loop electrosurgical excision procedure, LEEP, of high-grade cervical intraepithelial neoplasia. Tumori 88:478–480
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 521
EP 525
DI 10.1007/s12253-009-9148-y
PG 5
ER
PT J
AU Bori, R
Sejben, I
Svebis, M
Vajda, K
Marko, L
Pajkos, G
Cserni, G
AF Bori, Rita
Sejben, Istvan
Svebis, Mihaly
Vajda, Kornel
Marko, Laszlo
Pajkos, Gabor
Cserni, Gabor
TI Heterogeneity of pT3 Colorectal Carcinomas According to the Depth of Invasion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal carcinoma; TNM; Depth of invasion; Metastasis; Venous invasion
ID Colorectal carcinoma; TNM; Depth of invasion; Metastasis; Venous invasion
AB Colorectal carcinomas (CRCs) infiltrating through the muscularis propria layer without infiltration of adjacent structures, organs or the serosa—i.e. the pT3 tumors, compose the largest subset of large intestinal carcinomas treated by surgical resection. They are heterogeneous in terms of prognosis. CRCs treated by surgery in a period of 69 months were prospectively classified as pT3a tumors (invading to a maximum of 5 mm beyond the muscularis propria) and pT3b tumors (invading deeper). Their nodal status, incidence of vascular invasion and the presence or absence of distant metastases were analyzed in relation to the depth of invasion. Of the 593 CRCs primarily treated by surgery 429 were pT3 tumors. CRCs categorized as pT3a had significantly lower rates of nodal involvement (44% vs 75%), massive nodal involvement (pN2) (9% vs 39%), venous invasion (17% vs 30%) and distant metastasis (11% vs 28%) than pT3b tumors. Significant differences in these prognostic variables in pT3a and pT3b cancers were observed both for carcinomas of the colon and those of the rectum. Such differences were not obvious in further 66 ypT3 cases of rectal carcinoma receiving neoadjuvant treatment before surgery. Tumors in the pT3a category are associated with a better prognostic profile than pT3b tumors. This subdivision might be useful in both prognostication and treatment planning.
C1 [Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., 6000 Kecskemet, Hungary.
[Sejben, Istvan] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., 6000 Kecskemet, Hungary.
[Svebis, Mihaly] Bacs-Kiskun County Hospital, Department of SurgeryKecskemet, Hungary.
[Vajda, Kornel] Kiskunfelegyhaza City Hospital, Department of SurgeryKiskunfelegyhaza, Hungary.
[Marko, Laszlo] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Pajkos, Gabor] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38., 6000 Kecskemet, Hungary.
RP Bori, R (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, 6000 Kecskemet, Hungary.
EM boririta@hotmail.com
CR Cserni G, 2003, Nodal staging of colorectal carcinomas and sentinel nodes. J Clin Pathol 56:327–335
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 527
EP 532
DI 10.1007/s12253-009-9149-x
PG 6
ER
PT J
AU Nemeth, Zs
Szasz, MA
Somoracz,
Tatrai, P
Nemeth, J
Gyorffy, H
Szijarto, A
Kupcsulik, P
Kiss, A
Schaff, Zs
AF Nemeth, Zsuzsanna
Szasz, Marcell Attila
Somoracz, Aron
Tatrai, Peter
Nemeth, Julia
Gyorffy, Hajnalka
Szijarto, Attila
Kupcsulik, Peter
Kiss, Andras
Schaff, Zsuzsa
TI Zonula Occludens-1, Occludin, and E-cadherin Protein Expression in Biliary Tract Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adherens junction; Biliary tract cancer; Tight junction
ID Adherens junction; Biliary tract cancer; Tight junction
AB The incidence of cholangiocarcinomas originating from intrahepatic and extrahepatic bile ducts, as well as of gallbladder carcinoma is increasing worldwide. The malignant transformation of biliary epithelia involves profound alterations of proteins in the intercellular junctions, among others zonula occludens-1 (ZO-1), occludin, and E-cadherin. Each plays important role in the maintenance of epithelial cell polarity and regulation of cell growth and differentiation. Our aim was to investigate ZO-1, occludin, and E-cadherin immunohistochemical reactions in tissue microarray blocks containing 57 normal and 62 neoplastic biliary tract samples. We demonstrated that the tight junction components ZO-1, occludin, and E-cadherin are downregulated in carcinomas arising from various compartments of the biliary tract (normal intrahepatic and extrahepatic bile ducts, gallbladder) as compared with their normal sites of origin. These results were confirmed by discriminant analysis yielding clear separation of the three normal sample groups from carcinomas in the corresponding locations.
C1 [Nemeth, Zsuzsanna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Somoracz, Aron] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Tatrai, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Nemeth, Julia] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Gyorffy, Hajnalka] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Szijarto, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Kupcsulik, Peter] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Kakar S, Ferrell LD, 2007, Tumors of the liver, gallbladder and biliary tree. In: Fletcher CDM, ed, Diagnostic histopathology of tumors, 3rd edn. Elsevier Limited, Philadelphia, pp 417–462
Chuang SC, Lee KT, Tsai KB, et al, 2004, Immunohistochemical study of DPC4 and p53 proteins in gallbladder and bile duct cancers. World J Surg 28:995–1000
Bajor J, Bero T, GaramszegiM, et al, 2001, Common bile duct tumor in a young woman with ulcerative colitis. Orv Hetil 142:1231–1234
Hong SM, Kim MJ, Pi DY, et al, 2005, Analysis of extrahepatic bile duct carcinomas according to the New American Joint Committee on Cancer staging system focused on tumor classification problems in 222 patients. Cancer 104:802–810
Obama K, Ura K, Li M, et al, 2005, Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepatology 41:1339–1348
Lewis JT, Talwalkar JA, Rosen CB, et al, 2007, Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasia-carcinoma sequence. Am J Surg Pathol 31:907–913
Kobayashi S, Ohnuma N, Yoshida H, et al, 2006, Preferable operative age of choledochal dilation types to prevent patients with pancreaticobiliary maljunction from developing biliary tract carcinogenesis. Surgery 139:33–38
Gonzalez-Mariscal L, Lechuga S, Garay E, 2007, Role of tight junctions in cell proliferation and cancer. Prog Histochem Cytochem 42:1–57
Hartsock A, Nelson WJ, 2008, Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778(3):660–669
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Laurila JJ, Karttunen T, Koivukangas V, et al, 2007, Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis. J Histochem Cytochem 55:567–573
Kleeff J, Shi X, Bode HP, et al, 2001, Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer. Pancreas 23:259–265
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Ikenouchi J, Matsuda M, Furuse M, et al, 2003, Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci 116:1959–1967
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Farazi PA, Zeisberg M, Glickman J, et al, 2006, Chronic bile duct injury associated with fibrotic matrix microenvironment provokes cholangiocarcinoma in p53-deficient mice. Cancer Res 66:6622– 6627
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Orban E, Szabo E, Lotz G, et al, 2008, Different expression of Occludin and ZO-1 in primary and metastatic liver tumors. Pathol Oncol Res 14:299–306
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2009
VL 15
IS 3
BP 533
EP 539
DI 10.1007/s12253-009-9150-4
PG 7
ER
PT J
AU Ellsworth, ER
Hooke, AJ
Love, B
Ellsworth, LD
Shriver, DC
AF Ellsworth, E Rachel
Hooke, A Jeffrey
Love, Brad
Ellsworth, L Darrell
Shriver, D Craig
TI Molecular Changes in Primary Breast Tumors and the Nottingham Histologic Score
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Allelic imbalance; Grade; Mitosis; Nuclear atypia; Tubule formation
ID Allelic imbalance; Grade; Mitosis; Nuclear atypia; Tubule formation
AB Pathological grade is routinely used to stratify breast cancer patients into favorable and less favorable outcome groups. Mechanisms by which genomic changes in breast tumors specifically contribute to the underlying components of tumor grade – tubule formation, nuclear pleomorphism, and mitoses — are unknown. This study examined 26 chromosomal regions known to be altered in breast cancer in 256 invasive breast carcinomas. Differences in overall levels and patterns of allelic imbalance (AI) at each chromosomal region were compared for tumors with favorable (=1) and unfavorable (=3) scores for tubule formation, nuclear pleomorphism and mitotic count. Levels of AI were significantly different between samples with high and low scores for tubule formation (P<0.001), nuclear pleomorphism (P<0.001) and mitotic count (P<0.05). Significantly higher levels of AI were detected at regions 11q23 and 13q12 for tumors with reduced tubule formation, chromosomes 9p21, 11q23, 13q14, 17p13 and 17q12 for those with high levels of nuclear atypia, and chromosomes 1p36, 11q23, and 13q14 for those with high mitotic counts. Region 16q11-q22 showed significantly more AI events in samples with low nuclear atypia. Patterns of genetic changes associated with poorly-differentiated breast tumors were recapitulated by the individual components of the Nottingham Histologic Score. While frequent alteration of 11q23 is common for reduced tubule formation, high nuclear atypia and high mitotic counts, suggesting that this is an early genetic change in the development of poorly-differentiated breast tumors, alterations at the other seven loci associated with poorly-differentiated tumors may specifically influence cell structure, nuclear morphology and cellular proliferation.
C1 [Ellsworth, E Rachel] Henry M. Jackson Foundation for the Advancement of Military Medicine, Clinical Breast Care Project, 620 Seventh Street, 15963 Windber, PA, USA.
[Hooke, A Jeffrey] Walter Reed Army Medical Center, Clinical Breast Care ProjectWashington, DC, USA.
[Love, Brad] InvitrogenCarlsbad, CA, USA.
[Ellsworth, L Darrell] Windber Research Institute, Clinical Breast Care ProjectWindber, PA, USA.
[Shriver, D Craig] Walter Reed Army Medical Center, Clinical Breast Care ProjectWashington, DC, USA.
RP Ellsworth, ER (reprint author), Henry M. Jackson Foundation for the Advancement of Military Medicine, Clinical Breast Care Project, 15963 Windber, USA.
EM r.ellsworth@wriwindber.org
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Ellsworth RE, Hooke JA, Love B et al, 2008, Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors. Breast Cancer Res Treat 107:259–265
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Roylance R, Gorman P, Hanby A, Tomlinson I, 2002, Allelic imbalance analysis of chromosome 16q shows that grade I and grade III invasive ductal breast cancers follow different genetic pathways. J Pathol 196:32–36
Ellsworth DL, Shriver CD, Ellsworth RE, Deyarmin B, Somiari RI, 2003, Laser capture microdissection of paraffin-embedded tissues. Biotechniques 34:42–46
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Medintz IL, Lee C-CR, Wong WW et al, 2000, Loss of heterozygosity assay for molecular detection of cancer using energy-transfer primers and capillary array electrophoresis. Genome Res 10:1211–1218
Ellsworth RE, Ellsworth DL, Neatrour DM et al, 2005, Allelic imbalance in primary breast carcinomas and metastatic tumors of the axillary lymph nodes. Mol Cancer Res 3:71–77
Fitzgibbons PL, Page DL, Weaver D et al, 2000, Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124:966–978
Fechter A, Buettel I, Kuehnel E, Savelyeva L, Schwab M, 2007, Common fragile site RFA11G and rare fragile site FRA11B at 11q23.3 encompass distinct genomic regions. Genes Chromosomes Cancer 46:98–106
Srivastava N, Gochhait S, Gupta P, Bamezai RNK, 2008, Copy number alterations of the H2AFX gene in sporadic breast cancer patients. Genes Chromosomes Cancer 180:121–128
Bagchi A, Papazoglu C, Wu Y et al, 2007, CHD5 is a tumor suppressor at human 1p36. Cell 128:459–475
Ellsworth RE, Ellsworth DL, Love B et al, 2007, Correlation of levels and patterns of genomic instability with histological grading of DCIS. Ann Surg Onc 14:3070–3077
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Hanby AM, Kelsell DP, Potts HWet al, 2007, Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer. Int J Cancer 88:204–208
Patel KJ, Yu VP, Lee H et al, 1998, Involvement of Brca2 in DNA repair. Mol Cell 1:347–357
Han X, Saito H, Miki Y, Nakanishi A, 2008, A CRM1-mediated nuclear export signal governs cytoplasmic localization of BRCA2 and is essential for centrosomal localization of BRCA2. Oncogene 27:2969–2977
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 541
EP 547
DI 10.1007/s12253-009-9151-3
PG 7
ER
PT J
AU Salinas, RN
Lopes, TC
Palma, VP
Oshima, TC
Bueno, V
AF Salinas, R Natalia
Lopes, T Camila
Palma, V Patricia
Oshima, T Celina
Bueno, Valquiria
TI Lung Tumor Development in the Presence of Sphingosine 1-phosphate Agonist FTY720
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Urethane; FTY720; Apoptosis; Proliferation; CD4 + Tcell
ID Lung cancer; Urethane; FTY720; Apoptosis; Proliferation; CD4 + Tcell
AB Urethane is a chemical carcinogen which causes lung tumorigenesis in mice with similarities to human adenocarcinoma (AC). The sphingosine 1-phosphate agonist FTY720 administered to mice in doses above 5 mg/kg/day has been able to prevent hepatocellular carcinoma and bladder cancer. We used BALB/c mice in urethane-induced lung cancer model to investigate the effects of a lower dose of FTY720 (1 mg/kg/day). The benefits of FTY720 were associated with the time point of the compound administration. FTY720 30 Group presented lower incidence and smaller area of lung nodules, decreased PCNA and increased Caspase-3 expressions. The findings in FTY720 0 Group (nodule multiplicity and area, PCNA expression) were similar to Urethane Group suggesting that the administration of the compound at early time point did not affect lung tumor development. FTY720 90 Group presented the biggest nodule area which was associated with increased PCNA and decreased Caspase-3 expressions. FTY720 (30 days and 90 days) administration decreased CD4+splenocytes and blood lymphocytes which caused opposite effects in lung tumor development - impairment and improvement respectively. In conclusion, FTY720 in low dose did not provide lung tumor inhibition in mice but its administration 30 days after the chemical carcinogen (Urethane) injection was associated with impaired tumor development.
C1 [Salinas, R Natalia] Federal University of Sao Paulo, Immunology Division, Rua Botucatu 862, 4° andar, CEP 04023-900 Sao Paulo, SP, Brazil.
[Lopes, T Camila] Federal University of Sao Paulo, Immunology Division, Rua Botucatu 862, 4° andar, CEP 04023-900 Sao Paulo, SP, Brazil.
[Palma, V Patricia] USP Ribeirao Preto Medical School, Laboratory of Flow CytometryRibeirao Preto, SP, Brazil.
[Oshima, T Celina] Sao Paulo University School of Medicine, Department of PathologySao Paulo, SP, Brazil.
[Bueno, Valquiria] Federal University of Sao Paulo, Immunology Division, Rua Botucatu 862, 4° andar, CEP 04023-900 Sao Paulo, SP, Brazil.
RP Bueno, V (reprint author), Federal University of Sao Paulo, Immunology Division, CEP 04023-900 Sao Paulo, Brazil.
EM valquiria@nefro.epm.br;valquiriabueno@hotmail.com
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O'Donnell EP, Zerbe LK, Dwyer-Nield LDet al, 2006, Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis. Cancer Lett 241:197–202
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LaMontagne K, Littlewood-Evans A, Schnell Cet al, 2006, Antagonism of sphigosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res 66:221–231
Azuma H, Takahara S, Ichimaru Net al, 2002, Marked Prevention of Tumor Growth and Metastasis by a Novel Immunosuppressive Agent, FTY720, in Mouse Breast Cancer Models. Cancer Res 62:1410–1419
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 549
EP 554
DI 10.1007/s12253-009-9152-2
PG 6
ER
PT J
AU Ren, T
Jiang, B
Xing, X
Dong, B
Peng, L
Meng, L
Xu, H
Shou, Ch
AF Ren, Tingting
Jiang, Beihai
Xing, Xiaofang
Dong, Bin
Peng, Lirong
Meng, Lin
Xu, Huiyu
Shou, Chengchao
TI Prognostic Significance of Phosphatase of Regenerating Liver-3 Expression in Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PRL-3; Expression; Ovarian cancer; Immunohistochemistry; prognosis
ID PRL-3; Expression; Ovarian cancer; Immunohistochemistry; prognosis
AB Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in several human cancers and associated with tumor progression, invasion and metastasis. However, the correlation between PRL-3 expression and clinical outcome in ovarian cancer has not been studied. In the present study, we investigated the expression of PRL-3 in 119 ovarian cancers and 30 normal ovarian tissues by immunohistochemistry with an anti-PRL-3 mouse monoclonal antibody 3B6, and analyzed its relationship with clinicopathologic factors and survival. The results demonstrated that PRL-3 expression was significantly higher in ovarian cancers compared to normal ovarian tissues (P<0.001). PRL-3 expression is not correlated with patient age, menstruation, tumor size, histological type, residual tumor, or other clinical findings. The patients with PRL-3-positive tumors had a significant poor prognosis than those with PRL-3-negative tumors. Univariate analysis identified PRL-3 expression as a poor outcome predictor (HR 1.925, 95% CI, 1.046–3.544, P=0.035). Multivariate analysis indicated that PRL-3 expression was an independent prognostic factor of borderline significance (HR 1.695, 95% CI, 0.914–3.145, P=0.094). Our results suggest that PRL-3 may serve as a valuable marker for diagnosis of ovarian cancer and as a potential independent prognostic factor for ovarian cancer.
C1 [Ren, Tingting] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Jiang, Beihai] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Xing, Xiaofang] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Dong, Bin] Beijing Cancer Hospital & Institute, Core facilityBeijing, China.
[Peng, Lirong] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Meng, Lin] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Xu, Huiyu] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
[Shou, Chengchao] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 52 Fucheng Road, 100142 Beijing, China.
RP Shou, Ch (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 100142 Beijing, China.
EM scc@bjcancer.org
CR Cannistra SA, 2004, Cancer of the ovary. N Engl J Med 351:2519–2529
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 555
EP 560
DI 10.1007/s12253-009-9153-1
PG 6
ER
PT J
AU Bekasi, S
Zalatnai, A
AF Bekasi, Sandor
Zalatnai, Attila
TI Overexpression of Glucocorticoid Receptor in Human Pancreatic Cancer and in Xenografts. An Immunohistochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; Glucocorticoid receptor; Immunohistochemistry; Xenograft
ID Pancreatic cancer; Glucocorticoid receptor; Immunohistochemistry; Xenograft
AB Glucocorticoid receptor overexpression has been reported in a variety of human solid tumors, but much less in known about its presence in pancreatic cancer. Only one report is available in the literature, back to 1994, since that no peculiar attention has been paid to this issue. Immunohistochemical analysis of paraffin-embedded tissue sections was performed in human normal pancreata and well differentiated pancreatic adenocarcinomas (monoclonal primary antibody, ABCAM, Cambridge, UK). As positive control invasive ductal adenocarcinoma of the breast was used. In the normal non-tumorous pancreas a strong positivity was detected in all acinar cells, typically in the cytoplasm. Nuclear staining was not visible. The distribution of the positive reaction was homogenous. The ductal pancreatic carcinoma cells also displayed a strong positivity. The location of the immune reaction was mainly cytoplasmic but in some tumors a strong nuclear reaction was also noticed. In some slides acini remained also positive in the close vicinity of the tumor. Although the positivity of the ductal tumor cells was a constant finding in our samples, surprisingly, the liver metastasis was completely negative. Strong glucocorticoid receptor expression was also found in xenografted human pancreatic cancer showing a diffuse, mainly cytoplasmic positivity. Our studies have shown that the human pancreatic carcinomas do overexpress a strong glucocorticoid receptor positivity, but its significance is not clear. However, this finding might have a clinical relevance.
C1 [Bekasi, Sandor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 561
EP 566
DI 10.1007/s12253-009-9154-0
PG 6
ER
PT J
AU Blazsek, J
Dobo Nagy, Cs
Blazsek, I
Varga, R
Vecsei, B
Fejerdy, P
Varga, G
AF Blazsek, Jozsef
Dobo Nagy, Csaba
Blazsek, Istvan
Varga, Rita
Vecsei, Balint
Fejerdy, Pal
Varga, Gabor
TI Aminobisphosphonate Stimulates Bone Regeneration and Enforces Consolidation of Titanium Implant into a New Rat Caudal Vertebrae Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE New implant osseointegration model; Osteo-neogenesis; Aminobisphosphonates (Zometa®); Bone regeneration; Micro computer tomography (micro-CT); Biomechanical measurement
ID New implant osseointegration model; Osteo-neogenesis; Aminobisphosphonates (Zometa®); Bone regeneration; Micro computer tomography (micro-CT); Biomechanical measurement
AB Bisphosphonates are widely used as therapeutic agents in bone disorders including cancer metastasis due to their osteoclast inhibitory effect. Recent data shows that bisphosphonates may also induce bone-building by stimulating osteoblast activity. Clinical observations, however, have revealed that bisphosphonates may cause necrosis in the oral cavity which questions their usefulness in bone regeneration during the consolidation of inorganic implants. Here we report the investigation of bone neogenesis following chronic amine bisphosphonate (Zometa®) treatment in a novel experimental model, using the rat tail vertebra as a support. This method involves (1) implantation of titan screw into the tail vertebrae, (2) systemic bisphosphonate treatment and (3) quantitative biophysical measurements which mirrors consolidation of implant, i.e. strength of fixation and changes in newly formed bone architecture using micro Computer Tomograph (micro-CT). The degree of fixation of titan implants (osseointegration) increased by 36% on the effect of Zometa and the structure of newly formed bone became robust. The mass of new bone increased 3.1-fold at 6 weeks of regeneration, as compared to controls. Thus, Zometa®, a potent aminobisphosphonate used in therapy of cancer metastases, osteoporosis and bone marrow transplantation, significantly increased bone neogenesis and enforced osseointegration of titan implants as measured quantitatively in the rat tail vertebra. Our data support the usefulness of aminobisphosphonates in the rehabilitation of bone loss as well as in improvement osseointegration of implants. We emphasise that this novel method may open up new possibilities for screening the effects of local and systemic treatments.
C1 [Blazsek, Jozsef] Semmelweis University, Department of Oral Biology, Nagyvarad ter 4, 1089 Budapest, Hungary.
[Dobo Nagy, Csaba] Semmelweis University, Department of ProsthodonticsBudapest, Hungary.
[Blazsek, Istvan] Paul-Brousse Hospital, ICIG and Universite de Paris-Sud, INSERM U602 and U972Paris, France.
[Varga, Rita] Full-Tech CompanyBudapest, Hungary.
[Vecsei, Balint] Semmelweis University, Department of ProsthodonticsBudapest, Hungary.
[Fejerdy, Pal] Semmelweis University, Department of ProsthodonticsBudapest, Hungary.
[Varga, Gabor] Semmelweis University, Department of Oral BiologyBudapest, Hungary.
RP Blazsek, J (reprint author), Semmelweis University, Department of Oral Biology, 1089 Budapest, Hungary.
EM blajozs@net.sote.hu
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von Knoch F, Jaquiery C, Kowalsky M, Schaeren S, Alabre C, Martin I, Rubash HE, Shanbhag AS, 2005, Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials 34:6941–6949
Tauchmanova L, Ricci P, Serio B, Lombardi G, Colao A, Rotoli B, Selleri C, 2005, Short-term Zoledronic acid treatment increases bone mineral density and marrow clonogenic fibroblast progenitors after allogeneic stem cell transplantation. J Clin Endocrinol Metab 90:627–634
Ysander M, Branemark R, Olmarker K, Myers RR, 2001, Intramedullary osseointegration: development of a rodent model and study of histology and neuropeptide changes around titanium implants. J Rehabilit Res Dev 38:183–190
Naresh KN, Lampert I, Haserjian R, Lykiis D, Elerfiel K, Horncastle D, Smith N, Murray-Brown W, Stamp GW, 2006, Optimal processing of bone marrow trephine biopsy: the Hammersmith protocol. J Clin Pathol 59:903–911
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Saulacic N, Iizuka T, Martin MS, Garcia AG, 2008, Alveolar distraction osteogenesis: a systematic review. Int J Oral Maxillofac Surg 37:1–7
Shubayev VI, Branemark R, Steinauer J, Myers RR, 2004, Titanium implants induce expression of matrix metalloproteases in bone during osseointegration. J Rehab Res Dev 41:757–766
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Amital H, Applbaum YH, Vasiliev L, Rubinow A, 2004, Hypertrophic pulmonary osteoarthropathy: control of pain and symptoms with pamidronate. Clin Rheumatol 23:330–332
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Amant N, McDonald M, Godfrey C, Bilston L, Little D, 2007, Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res 22:867–876
Hashimoto T, Shigetomi M, Ohno T, Matsunaga T, Muramatsu K, Tanaka H, Sugiyama T, Taguchi T, 2007, Sequential treatment with intermittent low-dose human parathyroid hormone, 1–34, and bisphosphonate enhances large-size skeletal reconstruction by vascularized bone transplantation. Calcif Tissue Int 81(3):232–239
Mundy GR, Yoneda T, Hiraga T, 2001, Preclinical studies with zoledronic acid and other bisphosphonates: Impact on the bone microenvironment. Semin Oncol 28(6):35–44
Blazsek I, Chagraoui J, Peault B, 2000, Ontogenic emergence of the hematon, a morphogenic stromal unit that supports multipotential hemopoietic progenitors in mouse bone marrow. Blood 96:3763–3771
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden D, 2003, Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846
Blazsek I, Goldschmidt E, Machover D, Misset JL, Benavides M, Comisso M, Ceresi E, Canon C, Labat ML, Mathe G, 1986, Excess of lympho-reticular cell complexes in the bone marrow linked to T cell mediated dysmyelopoiesis. Biomed Pharmacother 40:28–32
Epling-Burnette PK, Painter JS, Rollison DE, Ku E, Vendron D, Widen R, Boulware D, Zou JX, Bai F, List AF, 2007, Prevalence and clinical association of clonal T-cell expansion in Myelodysplastic Syndrome. Leukemia 21:659–667
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 567
EP 577
DI 10.1007/s12253-009-9156-y
PG 11
ER
PT J
AU Pap, Zs
Pavai, Z
Denes, L
Kovalszky, I
Jung, J
AF Pap, Zsuzsanna
Pavai, Zoltan
Denes, Lorand
Kovalszky, Ilona
Jung, Janos
TI An Immunohistochemical Study of Colon Adenomas and Carcinomas: E-cadherin, Syndecan-1, Ets-1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon adenoma; Colon carcinoma; E-cadherin; Ets-1; Immunohistochemistry; Syndecan-1
ID Colon adenoma; Colon carcinoma; E-cadherin; Ets-1; Immunohistochemistry; Syndecan-1
AB It is thought that dysregulation of E-cadherin, syndecan-1 (CD138) and Ets-1 is involved in carcinoma development. E-cadherin is an important epithelial cell adhesion molecule; syndecan-1 (CD138) is a regulatory proteoglycan in both cell-cell and cell-matrix adhesion and Ets-1 is a proto-oncogene and transcription factor, which takes part in extracellular matrix remodeling. Our goal was to study the changes in the expression of these molecules during colon carcinoma development and progression. We tested 117 colon adenomas and 149 de novo and ex adenoma carcinomas of the colon, using the Ultravision Polymer system. The positive reaction rate was 100% for E-cadherin, 98.3% for syndecan-1 and 22.4% for Ets-1 in adenomas, while in carcinomas it was 88.5%, 62.4% and 56.3% respectively. We found decreasing expression of E-cadherin and syndecan-1 throughout colon carcinoma progression and an opposite regulation for the Ets-1 protein. Decrease in expression of syndecan-1 is more pronounced in carcinomas compared to E-cadherin. De novo carcinomas have lower E-cadherin and syndecan-1 expression, and higher Ets-1 expression compared to ex adenoma carcinomas. These findings support the hypothesis that there are differences in the carcinogenesis of these tumors.
C1 [Pap, Zsuzsanna] University of Medicine and Pharmacy Targu-Mures, Department of Anatomy and EmbryologyTargu-Mures, Romania.
[Pavai, Zoltan] University of Medicine and Pharmacy Targu-Mures, Department of Anatomy and EmbryologyTargu-Mures, Romania.
[Denes, Lorand] University of Medicine and Pharmacy Targu-Mures, Department of Anatomy and EmbryologyTargu-Mures, Romania.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jung, Janos] University of Medicine and Pharmacy Targu-Mures, Department of PathologyTargu-Mures, Romania.
RP Pap, Zs (reprint author), University of Medicine and Pharmacy Targu-Mures, Department of Anatomy and Embryology, Targu-Mures, Romania.
EM papzsuzsa@yahoo.com
CR Valean S, Mircea PA, Oprea L, 2006, Trends of mortality rates from gastric cancer and colorectal cancer in Romania, 1955–2003. J Gastrointestin Liver Dis 15(2):111–115
Hamilton RS, Aaltonen AL, 2000, Pathology and genetics, toumors of the digestive system. IARC Press, Lyon
Pecina-Slaus N, 2003, Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int 3:17
Day MR, Hao X, Mohammad I, Daszak P, Talbot IC, Forbes A, 1999, Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence. Virchows Arch 434:121–125
Beauvais DM, Rapraeger CA, 2004, Syndecans in tumor cell adhesion and signaling. RB&E 2:3 http://www.rbej.com/content/2/1/3
Nakayama T, Masahiro I, Akira O, Shinji N, Ichiro S, 2001, Expression of the ets-1 Proto-Oncogene in human colorectal carcinoma. Mod Pathol 14(5):415–422
Arun S, Watson KD, 2005, Ets transcription factors and their emerging roles in human cancer. Eur J Cancer 41:2462–2478
Nosho K, Yoshiday M, Yamamoto M, Taniguchi H, Adachi Y, Mikami M, Hinodal Y, Imai K, 2005, Association of Ets-related transcriptional factor E1AF expression with overexpression of matrix metalloproteinases, COX-2 and iNOS in the early stage of colorectal carcinogenesis. Carcinogenesis 26(5):892–899
Behrens P, Mathiak M, Mangold E, Kirdorf S, Wellmann A, Fogt F, Rothe M, Florin A, Wernert N, 2003, Stromal expression of invasion-promoting matrix-degrading proteases MMP-1 and -9 and the Ets-1 transcription factor in HNPCC carcinomas and sporadic colorectal cancers. Int J Cancer 107:183–188
Khoursheed MA, Mathew TC, Makar RR, Louis S, Asfar SK, Al- Sayer HM, Dashti HM, Al-Bader A, 2003, Expression of E-cadherin in human colorectal cancer. Surg J R Coll Surg Edinb Irel 86–91
Elzagheid A, Algars A, Bendardaf R, Lamlum H, Ristamaki R, Collan Y, Syrjanen K, Pyrhonen S, 2006, E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol 12(27):4304– 4309
Fujiya M, Watari J, Ashida T, Honda M, Tanabe H, Fujiki T, Saitoh Y, Kohgo Y, 2001, Reduced expression of syndecan-1 affects metastatic potential and clinical outcome in patients with colorectal cancer. Jpn. J Cancer Res 192:1074–1081
Lundin M, Nordling S, Lundin J, Isola J, Wiksten JP, Haglund C, 2005, Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer. Oncology 68:306–313
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Geller SA, Dhall D, Alsabeh R, 2008, Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas. Arch Pathol Lab Med 132:490– 499
Wlodarczyk J, Bethke B, Mueller E, Stolte M, Mueller J, 2001, A comparative study of E-cadherin and stromelysin-3 expression in de novo and ex adenoma carcinoma of the colorectum. Virchows Arch 439:756–761
Batistatou A, Charalabopoulos AK, Scopa CD, Nakanishi Y, Kappas A, Hirohashi S, Agnantis NJ, Charalabopoulos K, 2006, Expression patterns of dysadherin and E-cadherin in lymph node metastases of colorectal carcinoma. Virchows Arch 448:763–767
Peretti T, Waisberg J, Mader AM, Matos L, Costa R, Conceicao G, Lopes A, Nader H, Pinhal M, 2008, Heparanase-2, syndecan- 1, and extracellular matrix remodeling in colorectal carcinoma. Eur J Gastroenterol & Hepatol 20:756–765
Gottardi JC, Wong E, Gumbiner MB, 2001, E-Cadherin suppresses cellular transformation by inhibiting β-catenin signaling in an adhesion-independent manner. J Cell Biol 153(5):1049–1059
Qinglang L, Pyong WP, Wilson LC, Parks CW, 2002, Matrilysin shedding of syndecan-1 regulates Chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 111:635–646
Fitzgerald LM, Wang Z, Park WP, Murphy G, Bernfield M, 2000, Shedding of syndecan-1 and -4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase. J. Cell Biol 148(4):811–824
Hashimoto Y, Skacel M, Adams JC, 2008, Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: an immunohistochemical study of clinically annotated tumors. BMC Cancer 8(185):1–7
Kwak JM, Min BW, Lee JH, Choi JS, Lee SI, Park SS, Kim J, Um JW, Kim SH, Moon HY, 2007, The prognostic significance of Ecadherin and liver intestine-cadherin expression in colorectal cancer. Dis Colon Rectum 50:1873–1880
Dilek F, Topak N, Aktepe F, Sahin O, Turel KS, Sahin DA, Dilek ON, 2008, E-cadherin, β-catenin adhesion complex and relation to matrilysin expression in pT3 rectosigmoid cancers. Pathol Res Practice 204(11):809–815
Tetsuji T, Koji M, Tsuyoshi H, 2006, Colorectal cancer: genetics of development and metastasis. J Gastroenterology 41:185–192
Ortega P, Moran A, de Juan C, Frias C, Hernandez S, Lopez-Asenjo J-A, Sanchez-Pernaute A, Torres A, Iniesta P, Benito M, 2008, DifferentialWnt pathway gene expression and E-cadherin truncation in sporadic colorectal cancers with and without microsatellite instability. Clin Cancer Res 14(4):995–1001
Jurgen D, 2003, The biology of the Ets1 proto-oncogene. Mol Cancer 2:29 http://www.molecular-cancer.com/content/2/1/29
McGuire KJ, Qinglang L, Parks CW, 2003, Matrilysin, Matrix Metalloproteinase-7, mediates E-Cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 162(6):1831–1843
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 579
EP 587
DI 10.1007/s12253-009-9157-x
PG 9
ER
PT J
AU Zhao, ZSh
Wang, YY
Ye, ZY
Tao, HQ
AF Zhao, Zhong-Sheng
Wang, Yuan-Yu
Ye, Zai-Yuan
Tao, Hou-Quan
TI Prognostic Value of Tumor-Related Molecular Expression in Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Basic fibroblast growth factor; Matrix metalloproteinase-9; Urokinase plasminogen activator; Prognosis; Molecular markers
ID Gastric cancer; Basic fibroblast growth factor; Matrix metalloproteinase-9; Urokinase plasminogen activator; Prognosis; Molecular markers
AB In order to identify reliable molecular markers for prognostic prediction in gastric carcinoma, we evaluated the expression of six molecular markers, namely bFGF, IGF-2, HGF, MMP-9, integrin β3 and uPA in gastric cancer. There was a significant correlation between the expression of these markers and the depth of tumor invasion, vessel invasion, lymph node and distant metastasis, TNM stage and microvessel density. The average survival time and 5-year survival rate of patients with positive expression of molecular markers was higher than those with negative expression. Multivariate analysis showed that abnormal expression of bFGF, MMP-9 and uPA, as well as depth of invasion, lymph node and distant metastasis and TNM stage were independently related to poor prognosis of gastric cancer. MMP-9, bFGF and uPA are potential candidates for development as clinically applicable molecular prognostic markers for gastric carcinoma, and may be effective therapeutic targets for the disease in the future.
C1 [Zhao, Zhong-Sheng] Zhejiang Provincial People’s Hospital, Department of Pathology, 158 shangtang road, 310014 Hangzhou, China.
[Wang, Yuan-Yu] Zhejiang Provincial People’s Hospital, Department of General SurgeryHangzhou, China.
[Ye, Zai-Yuan] Zhejiang Provincial People’s Hospital, Department of General SurgeryHangzhou, China.
[Tao, Hou-Quan] Zhejiang Provincial People’s Hospital, Department of General SurgeryHangzhou, China.
RP Zhao, ZSh (reprint author), Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
EM lywyy1979@hotmail.com
CR Inoue M, Tsugane S, 2005, Epidemiology of gastric cancer in Japan. Postgrad Med J 81:419–424
Wenhua Z, Fanghai H, 2008, Surgical therapy of gastric cancer in china. Journal of Practical oncology 23:91–93
Egeblad M, Werb Z et al, 2002, New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161– 174
Moon WS, Park HS, Yu KH et al, 2006, Expression of angiopoietin 1, 2 and their common receptor Tie2 in human gastric carcinoma: in implication for angiogenesis. Journal of Korean Medical Science 21:272–278
Niedergethmann M, Hildenbrand R, Wostbrock B et al, 2002, High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas 25:122–129
Kolev Y, Uetake H, Iida S et al, 2007, Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Annals of Surgical Oncology 14:2738–2747
Mizokami K, Kakeji Y, Oda S et al, 2006, Clinicopathologic significance of hypoxia-inducible factor 1 alpha overexpression in gastric carcinomas. Journal of Surgical Oncology 94:149–154
Weidner N, Semple JP, Welch WR, Folkman J, 1991, Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1–8
Hundahl SA, Phillips JL, Menck HR, 2000, The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: fifth edition American Joint Committee on cancer staging, proximal disease, and the ‘different disease’ hypothesis. Cancer 88:921–932
Park M, Park H, Kim WH, Cho H, Lee JH, 2005, Presence of autocrine hepatocyte growth factor-Met signaling and its role in proliferation and migration of SNU-484 gastric cancer cell line. Exp Mol Med 37:213–219
Niki M, Iso Zaki H, Toyoda M et al, 1999, Serum human hepatocyte growth factor is elevated in patients with metastatic gastric carcinoma. Hepatogastroenterology 46:568–573
Yi HK, Hwang PH, Yang DH, Kang CW, Lee DY, 2001, Expression of the insulin-like growth factors, IGFs, and the IGFbinding proteins, IGFBPs, in human gastric cancer cells. Eur J Cancer 37:2257–2263
Niu JX, Zhang WJ, Ye LY, 2007, The role of adhesion molecules, alpha v beta 3, alpha v beta 5 and their ligands in the tumor cell and endothelial cell adhesion. Eur J Cancer Prev 16:517–527
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Zhang S, Li L, Lin JY, Lin H, 2003, Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma. World J Gastroenterol 9:899–904
Kaneko T, Konno H, Baba M, 2003, Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci 94(1):43–49
Yang SF, Hsieh YS, Lin CL, 2005, Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients. Clin Chim Acta 354:91–99
Gao ZL, Zhang C, Du GY, Lu ZJ, 2007, Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma. Hepatogastroenterology 54:1591–1595
Zhao J, Liu XY, Zhang QY, Jiang W, 2005, Plasma level and prognostic significance of VEGF, bFGF and MMP-9 in patients with advanced non-small-cell lung cancer. Zhonghua Zhong Liu Za Zhi 27:676–679
Ramos-Desimone N, Haha-Dantona E, Siply J et al, 1999, Activation of matrix metalloproteinases 9 Via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274:13066–13076
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Lee SR, Guo SZ, Scannevin RH, 2007, Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators. Neurosci Lett 417:1–5
Zhao Y, Lyons CE Jr, Xiao A, 2008, Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochem Biophys Res Commun 369:1215–1220
Sapienza P, di Marzo L, Borrelli V, 2004, Basic fibroblast growth factor mediates carotid plaque instability through metalloproteinase-2 and -9 expression. Eur J Vasc Endovasc Surg 28:89–97
Rao JS, Gondi C, Chetty C, 2005, Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirusmediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells. Mol Cancer Ther 4:1399–1408
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 589
EP 596
DI 10.1007/s12253-009-9158-9
PG 8
ER
PT J
AU Fodor, A
Molnar, ZsM
Krenacs, L
Bagdi, E
Csomor, J
Matolcsy, A
Demeter, J
AF Fodor, Aniko
Molnar, Zsolt Miklos
Krenacs, Laszlo
Bagdi, Eniko
Csomor, Judit
Matolcsy, Andras
Demeter, Judit
TI Autoimmune Hemolytic Anemia as a Risk Factor of Poor Outcome in Patients with Splenic Marginal Zone Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autoimmune hemolytic anemia; Splenic marginal zone lymphoma; Prognosis; Outcome
ID Autoimmune hemolytic anemia; Splenic marginal zone lymphoma; Prognosis; Outcome
AB Splenic marginal zone lymphoma is a rare disease, accounting for 1% of all lymphomas. We reviewed our single center experience of 13 patients with splenic marginal zone lymphoma (SMZL). Based on the prognostic model developed by Intergruppo Italiano Linfomi, 31% (4/13) of our patients had good, 38% (5/13) had intermediate and 31% (4/13) had a poor prognosis. The presence of two out of three prognostic factors (anemia, elevated LDH, low serum albumin) assignes the patient into the high risk category. In patients with anemia and an elevated LDH due to hemolysis, the outcome seems to be especially poor. Three out of 13 (23%) cases were complicated by autoimmune hemolytic anemia. All patients with autoimmune hemolytic anaemia (AIHA) died 7–28 months after the diagnosis. The mean follow-up time of those nine patients who are still alive is longer than 5 years (36–100 months). Patients with AIHA had significantly (p<0.001) worse survival than those without AIHA. The main finding of our study is that the presence of AIHA is an adverse prognostic factor in SMZL.
C1 [Fodor, Aniko] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, H-1083 Budapest, Hungary.
[Molnar, Zsolt Miklos] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, H-1083 Budapest, Hungary.
RP Demeter, J (reprint author), Semmelweis University, 1st Department of Internal Medicine, H-1083 Budapest, Hungary.
EM demjud@bel1.sote.hu
CR Dogan A, 2005, Modern histological classification of low grade B-cell lymphomas. Best Pract Res Clin Haematol 18:11–26
Schmid C, Kirkham N, Diss T, Isaacson PG, 1992, Splenic marginal zone cell lymphoma. Am J Surg Pathol 16:455–466
Melo JV, Robinson DS, Gregory C, Catovsky D, 1987, Splenic B cell lymphoma with “villous” lymphocytes in the peripheral blood: a disorder distinct from hairy cell leukemia. Leukemia 1:294–298
Isaacson PG, Matutes E, Burke M, Catovsky D, 1994, The histopathology of splenic lymphoma with villous lymphocytes. Blood 84:3828–3834
Matutes E, Oscier D, Montalban C et al, 2008, Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia 22:487–495
Arcaini L, Lazzarino M, Colombo N et al, 2006, Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood 107:4643–4649
Thieblemont C, Felman P, Berger F et al, 2002, Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients. Clin Lymphoma 3:41–47
Thieblemont C, Felman P, Callet-Bauchu E et al, 2003, Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol 4:95–103
Chacon JI, Mollejo M, Munoz E et al, 2002, Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients. Blood 100:1648–1654
Parry-Jones N, Matutes E, Gruszka-Westwood AM et al, 2003, Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients. Br J Haematol 120:759–764
Camacho FI, Mollejo M, Mateo MS et al, 2001, Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases. Am J Surg Pathol 25:1268– 1276
Dungarwalla M, Appiah-Cubi S, Kulkarni S et al, 2008, Highgrade transformation in splenic marginal zone lymphoma with circulating villous lymphocytes: the site of transformation influences response to therapy and prognosis. Br J Haematol 143:71–74 Epub 2008 Jul 30
Cualing H, Steele P, Zellner D, 2000, Blastic transformation of splenic marginal zone B-cell lymphoma. Arch Pathol Lab Med. 124:748–752
Gale R, Smith OP, Wood M, Mehta AB, 1992, Splenic lymphoma with villous lymphocytes complicated by autoimmune haemolytic anaemia. Lancet 340:1106
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 597
EP 603
DI 10.1007/s12253-009-9159-8
PG 7
ER
PT J
AU Kuncova, K
Janda, A
Kasal, P
Zamecnik, J
AF Kuncova, Klara
Janda, Ales
Kasal, Pavel
Zamecnik, Josef
TI Immunohistochemical Prognostic Markers in Intracranial Ependymomas: Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ependymoma; Immunohistochemistry; Ki-67; Meta-analysis; MIB-1; prognosis
ID Ependymoma; Immunohistochemistry; Ki-67; Meta-analysis; MIB-1; prognosis
AB Distinction between grade II ependymomas and anaplastic ependymomas based on histopathological examination solely is problematic and, therefore, the management of intracranial ependymomas remains controversial. The aim of this study was to conduct a systematic review (SR) and meta-analysis (MA) of data published on immunohistochemical prognostic markers (IPM) in intracranial ependymomas (IE), and to establish an evidencebased perspective on their clinical value. Following the extensive search based on a strictly defined group of key words, 30 studies reporting results on IPM in IE were identified. Due to a pronounced inter-study heterogeneity, only 14 publications fulfilled the criteria for inclusion into SR. From the total of 67 immunohistochemical markers, 18 were found to correlate with prognosis. However, owing to inadequate data publishing, MA could be performed only with data on proliferation marker MIB-1 (Ki-67) from 5 publications, including 337 patients: The pooled hazard ratio for overall survival was 3.16 (95% confidence interval=1.96–5.09; p<0.001) implicating that patients suffering from tumors with higher immunohistochemical expression of MIB-1 had a significantly worse outcome. Marked inter-study heterogeneity and incomplete data publishing in primary studies significantly limited extent of the SR, and the possibility of performing MA. Although the prognostic impact of MIB-1 immunoexpression in IE could be confirmed, there remains lack of further reliable IPM that could be used in routine diagnosis. We encourage to search for new, useful markers, as well as to standardize lab-techniques and data interpretation algorithms across laboratories in order to increase data compatibility.
C1 [Kuncova, Klara] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of PathologyPrague, Czech Republic.
[Janda, Ales] Charles University, 2nd Medical School and University Hospital Motol, Department of Medical InformaticsPrague, Czech Republic.
[Kasal, Pavel] Charles University, 2nd Medical School and University Hospital Motol, Department of Medical InformaticsPrague, Czech Republic.
[Zamecnik, Josef] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of PathologyPrague, Czech Republic.
RP Zamecnik, J (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Prague, Czech Republic.
EM josef.zamecnik@lfmotol.cuni.cz
CR McLendon RE, Wiestler OD, Kros JM, Korshunov A, Ng HK, 2007, Ependymoma. In: Louis DN, Wiestler OD, Cavanee WK, eds, Classification of the Tumours of the Central Nervous System. Lyon, International Agency for Research on Cancer, IARC)
Foreman NK, Love S, Thorne R, 1996, Intracranial ependymomas: analysis of prognostic factors in a population-based series. Pediatr Neurosurg 24:119–25
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 605
EP 614
DI 10.1007/s12253-009-9160-2
PG 10
ER
PT J
AU Hashimoto, Y
Tsukamoto, N
Nakahashi, H
Yokohama, A
Saitoh, T
Handa, H
Matsushima, T
Murakami, H
Nojima, Y
Karasawa, M
AF Hashimoto, Yoko
Tsukamoto, Norifumi
Nakahashi, Hirotaka
Yokohama, Akihiko
Saitoh, Takayuki
Handa, Hiroshi
Matsushima, Takafumi
Murakami, Hirokazu
Nojima, Yoshihisa
Karasawa, Masamitsu
TI Hairy Cell Leukemia-Related Disorders Consistently Show Low CD27 Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hairy cell leukemia; HCL-Japanese variant; HBLD; CD27; IgVH; DRB1*04
ID Hairy cell leukemia; HCL-Japanese variant; HBLD; CD27; IgVH; DRB1*04
AB In Japan, typical hairy cell leukemia (HCL) is rare, and HCL-Japanese variant (HCL-JV) is more common. Hairy B-cell lymphoproliferative disorder (HBLD) is another unusual disorder of polyclonal B-lymphocytosis of hairy cell appearance. In the present study, we analyzed the clinical features of 3 patients with HCL, 3 with HCL-JV, and 3 with HBLD. All HBLD patients had the DRB1*04 allele. As compared with other B-cell lymphoproliferative disorders, CD27 expression on B cells was significantly lower in all patients, ranging from 0.3% to 23.4%. Our results suggest that low CD27 expression may be a distinct feature of these HCL-related disorders.
C1 [Hashimoto, Yoko] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Tsukamoto, Norifumi] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Nakahashi, Hirotaka] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Yokohama, Akihiko] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Saitoh, Takayuki] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Handa, Hiroshi] Gunma University, Faculty of Medicine, School of Health ScienceMaebashi, Gunma, Japan.
[Matsushima, Takafumi] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Murakami, Hirokazu] Gunma University, Faculty of Medicine, School of Health ScienceMaebashi, Gunma, Japan.
[Nojima, Yoshihisa] Gunma University, Graduate School of Medicine, Department of Medicine and Clinical ScienceMaebashi, Gunma, Japan.
[Karasawa, Masamitsu] Gunma University, Faculty of Medicine, Blood Transfusion Service, University Hospital, 3-39-15 Showa-machi, 371-8511 Maebashi, Gunma, Japan.
RP Karasawa, M (reprint author), Gunma University, Faculty of Medicine, Blood Transfusion Service, University Hospital, 371-8511 Maebashi, Japan.
EM karasawa@showa.gunma-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 615
EP 621
DI 10.1007/s12253-009-9161-1
PG 7
ER
PT J
AU Ren, T
Xu, L
Jiao, Sh
Wang, Y
Cai, Y
Liang, Y
Zhou, Y
Zhou, H
Wen, Z
AF Ren, Tao
Xu, Lin
Jiao, Shuxian
Wang, Yanying
Cai, Yingyun
Liang, Yongjie
Zhou, Ya
Zhou, Hong
Wen, Zhenke
TI TLR9 Signaling Promotes Tumor Progression of Human Lung Cancer Cell In Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CpG oligonucleotide; Lung cancer; TLR9; Tumor progression; Tumor immunity
ID CpG oligonucleotide; Lung cancer; TLR9; Tumor progression; Tumor immunity
AB Toll like receptor 9 (TLR9) was identified mainly in cells of the immune system, and CpG oligonucleotides (CpG ODN), which induces signaling through TLR9, are currently under investigation as adjuvants in clinical therapies against cancer. However, accumulating data suggested that functional TLR9 was also expressed in tumor cells and the effects of TLR9 signaling on the progression of tumor cells remain undefined. Our previous study demonstrated that the TLR9 signaling could significantly enhance the metastatic potential of human lung cancer cells in vitro. Here we carefully evaluated the direct effect of TLR9 signaling on tumor progression of human lung cancer cells in vitro and in vivo. We observed that TLR9 agonist CpG ODN could robustly enhance the tumor progression of 95D cells which expressed high level of TLR9 in nude mice. Furthermore, the CpG ODN could effectively induce the proliferation and IL-10 secretion of 95D cells in vitro. Finally, we demonstrated that CpG ODN could significantly elevate the tumor progression of TLR9 modifying 95C cells in vitro and in vivo, which could be dramatically abrogated by the inhibitory CpG ODN. Our findings indicated that the TLR9 signaling could promote the tumor progression of human tumor cells, which might provide novel insight into the implications for CpG based anti-tumor therapies.
C1 [Ren, Tao] Tongji University, East Hospital, Department of Respiratory MedicineShanghai, China.
[Xu, Lin] Zunyi Medical College, Department of ImmunologyGuizhou, China.
[Jiao, Shuxian] Qingdao Blood Center, Department of Central Laboratory, 266071 Qingdao, Shandong Province, China.
[Wang, Yanying] Fudan University, Zhongshan Hospital, Department of GerontologyShanghai, China.
[Cai, Yingyun] Fudan University, Zhongshan Hospital, Department of GerontologyShanghai, China.
[Liang, Yongjie] Tongji University, East Hospital, Department of Respiratory MedicineShanghai, China.
[Zhou, Ya] Zunyi Medical College, Department of Medical PhysicsGuizhou, China.
[Zhou, Hong] Qingdao Blood Center, Department of Central Laboratory, 266071 Qingdao, Shandong Province, China.
[Wen, Zhenke] Qingdao Blood Center, Department of Central Laboratory, 266071 Qingdao, Shandong Province, China.
RP Wen, Z (reprint author), Qingdao Blood Center, Department of Central Laboratory, 266071 Qingdao, China.
EM wenzk@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 623
EP 630
DI 10.1007/s12253-009-9162-0
PG 8
ER
PT J
AU Szabo, VG
Kunstar, A
Acsady, Gy
AF Szabo, Viktor Gabor
Kunstar, Aliz
Acsady, Gyorgy
TI Methylentetrahydrofolate Reductase and Nitric Oxide Synthase Polymorphism in Patients with Atherosclerosis and Diabetes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nitric oxide synthase; Methylentetrahydrofolate reductase; Polymorphism; Atherosclerosis; Cardiovascular Risk
ID Nitric oxide synthase; Methylentetrahydrofolate reductase; Polymorphism; Atherosclerosis; Cardiovascular Risk
AB The development of the atherosclerosis is based on multifactorial causes. In addition to the traditional risk factors, gene polymorphisms can play a role in the disease. Therefore in this study we investigated whether the eNOS and MTHFR gene polymorphisms is associated with myocardial infarction and stroke in patients with or without diabetes. We have identified polymorphisms in the NOS 3 gene and one of these polymorphisms, Glu298→Asp, was found to be a major risk factor for carotid artery disease and myocardial infarction. Our results indicate that the MTHFR G677T allele is significantly associated with MI. MTHFR 677 G/T genotyping may be of clinical importance as a prognostic and therapeutic marker, although further studies are needed to substantiate this hypothesis.
C1 [Szabo, Viktor Gabor] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor str. 68, H-1122 Budapest, Hungary.
[Kunstar, Aliz] National Institute of OncologyBudapest, Hungary.
[Acsady, Gyorgy] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor str. 68, H-1122 Budapest, Hungary.
RP Szabo, VG (reprint author), Semmelweis University, Department of Cardiovascular Surgery, H-1122 Budapest, Hungary.
EM szabogvdr@gmail.com
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Pallaud C, Sass C, Zannad F, Siest G, Visvikis S, 2001, APOC3, CETP, fibrinogen, and MTHFR are genetic determinants of carotid intima-media thickness in healthy men, the Stanislas cohort). Clin Genet 59:316–324
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 631
EP 637
DI 10.1007/s12253-009-9163-z
PG 7
ER
PT J
AU Baranyay, F
AF Baranyay, Ferenc
TI Histochemical Contributions to the Binding Mechanism of Complement (CR1, CR2) Receptors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CR1; CR2-reversible tissue adherence of E(A) C3b; E(A)C3d
ID CR1; CR2-reversible tissue adherence of E(A) C3b; E(A)C3d
AB Complement receptors (CR1, CR2, CR3), and their ligands (C3b, C3d, iC3b) are essentially involved in germinal center development and in binding, trapping, and retaining immunocomplexes. Methods studying complement receptor (CR1/CR2)-ligand (C3b/C3d) interactions mostly involve coating of sheep erythrocytes (E), sheep erythrocyte-antisheep erythrocyte antibody (EA complexes) and whole human (h) or mouse (m) sera as a source of complement, EACh/m complexes, as reagents. The observation of Dukor et al. (1970), that EACm complexes in native cryostat sections bind selectively and very strongly to the B lymphocyte regions of lymphoid organs allowed the topo-histochemical analysis of receptor (CR1/CR2)—ligand (C3b/C3d) interactions in such an immunologically important area as the germinal centers. The main finding of this study is, that periodic acid pretreatment of unfixed cryostat tonsil sections-oxidizing vicinal glycol groups of polysaccharide chains into dialdehydes-completely abolished the binding of all EAC/EC complexes to germinal center area. It may suggest the involvement of receptor carbohydrate in C3 receptor/ligand binding. In addition to, the subsequent sodium borohydride reduction-converting aldehydes (produced by periodic acid oxidation) into primary alcohols-restored selectively the binding of all applied EAC/EC complexes to follicular centers. These in vitro topo-histochemical studies give a strong hint for the participation of—OH groups of sugar residues in CR1/CR2 ligand (C3b/C3d) binding.
C1 [Baranyay, Ferenc] Medical University of Pecs, Dorottya Kanizsai Hospital, Szekeres J. u. 2-8, 8801 Nagykanizsa, Hungary.
RP Baranyay, F (reprint author), Medical University of Pecs, Dorottya Kanizsai Hospital, 8801 Nagykanizsa, Hungary.
EM fbaranyay@hotmail.com
CR Bara J, Decaens C, Loridon-Rosa B, Oriol R, 1992, Immunohistological characterization of mucin epitopes by pre-treatment of gastro-intestinal sections with periodic acid. J Immunol Methods 149:105–113
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Clamp JR, Hough L, 1965, The periodate oxidation of amino acids with reference studies to glycoproteins. Biochem J 94:17–24
Dierich MP, Scheiner O, Mussel HH, Hamman KP, Schopf RE, Schutz Z, 1982, Characterisation of complement receptors. Molecular Immunology 19:1201–1204
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 639
EP 644
DI 10.1007/s12253-009-9164-y
PG 6
ER
PT J
AU Roberts, SS
Mendonca-Torres, CM
Jensen, K
Francis, LG
Vasko, V
AF Roberts, S Stephen
Mendonca-Torres, Cecilia Maria
Jensen, Kirk
Francis, L Gary
Vasko, Vasyl
TI GABA Receptor Expression in Benign and Malignant Thyroid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; GABA receptors; Gene expression; Immunohistochemistry; Thyroid
ID Cancer; GABA receptors; Gene expression; Immunohistochemistry; Thyroid
AB Neurotransmitter systems have recently been shown to be involved in multiple malignancies including breast, colon and prostate cancers. The role of neurotransmitters and neurotrophic factors has not yet been examined in thyroid cancer. To determine the possible involvement of neurotransmitter systems in thyroid carcinogenesis we characterized the patterns of gammaaminobutyric acid (GABA) receptor expression in normal thyroid and thyroid tumors. We examined the expression patterns of the GABAergic system in 70 human thyroid tumor samples (13 follicular adenomas, 14 follicular carcinomas, 43 papillary carcinomas) and adjacent normal thyroid by immunohistochemistry. GABAergic system mRNA expression in thyroid cancer cell lines derived from primary (FTC133) and metastatic tumors (FTC236 and FTC238) was examined by real time PCR. Overall, GABA receptor expression is increased in tumors compared to normal thyroid tissue. Expression of GABAA receptor β2 was detected in the vasculature of normal thyroid and thyroid tumors but not in thyroid cancer cells. GABAA α2 was detected in metastatic-derived but not in primary-tumor derived cell lines. Expression levels of GABAB R2 and GABA receptor associated protein (GABARAP) are increased in adenomas and thyroid cancer suggesting their role in early stages of thyroid tumorigenesis. This study represents the first demonstration of GABA receptor expression in human thyroid tissue and suggests that the GABAergic system is involved in thyroid carcinogenesis.
C1 [Roberts, S Stephen] Uniformed Services University of the Health Sciences, Department of Pediatrics, 4301 Jones Bridge Road, 20814 Bethesda, MD, USA.
[Mendonca-Torres, Cecilia Maria] Uniformed Services University of the Health Sciences, Department of Pediatrics, 4301 Jones Bridge Road, 20814 Bethesda, MD, USA.
[Jensen, Kirk] Uniformed Services University of the Health Sciences, Department of Pediatrics, 4301 Jones Bridge Road, 20814 Bethesda, MD, USA.
[Francis, L Gary] Uniformed Services University of the Health Sciences, Department of Pediatrics, 4301 Jones Bridge Road, 20814 Bethesda, MD, USA.
[Vasko, Vasyl] Uniformed Services University of the Health Sciences, Department of Pediatrics, 4301 Jones Bridge Road, 20814 Bethesda, MD, USA.
RP Roberts, SS (reprint author), Uniformed Services University of the Health Sciences, Department of Pediatrics, 20814 Bethesda, USA.
EM sroberts@usuhs.mil
CR Ries LAG, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK, 2008, SEER Cancer Statistics Review, 1975–2005. via http://seer.cancer.gov/ csr/1975_2005/ Cited 04 December 2008
DeGroot LJ, Kaplan EL, McCormick M, Straus FH, 1990, Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 71:414–424
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 645
EP 650
DI 10.1007/s12253-009-9165-x
PG 6
ER
PT J
AU Chen, HJ
Mok, ST
Chen, ZH
Guo, AL
Zhang, XCh
Su, J
Wu, YL
AF Chen, Hua-Jun
Mok, S Tony
Chen, Zhi-Hong
Guo, Ai-Lin
Zhang, Xu-Chao
Su, Jian
Wu, Yi-Long
TI Clinicopathologic and Molecular Features of Epidermal Growth Factor Receptor T790M Mutation and c-MET Amplification in Tyrosine Kinase Inhibitor-resistant Chinese Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-MET; Epidermal growth factor receptor; Non-small cell lung cancer ; Resistance; T790M
ID c-MET; Epidermal growth factor receptor; Non-small cell lung cancer ; Resistance; T790M
AB To investigate the clinicopathologic and molecular features of the T790M mutation and c-MET amplification in a cohort of Chinese non-small cell lung cancer (NSCLC) patients resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). EGFR TKI-resistant NSCLC patients (n=29) and corresponding tumor specimens, and 53 samples of postoperative TKI-naive NSCLC patients were collected. EGFR exon 19, 20, and 21 mutations were analyzed. And c-MET gene copy number was determined. The EGFR T790M mutation in exon 20 was not detected in the population of 53 TKI-naive patients, but found in 48.3% (14/29) of the enrolled TKI-resistant patients. c-MET was amplified in 3.8% (2/53) of the TKI-naive NSCLC patients and highly amplified in 17.2% (5/29) of the cohort. Most of T790M mutations were frequently associated with non-smoker, adenocarcinoma and EGFR activating mutations. Three male patients with T790M mutation occurred with wild-type EGFR, and were resistant to the treatments following TKI resistance. Features of c-MET amplification in TKI-naive patients were indistinguishable from TKI-resistant patients. In the group of wild-type EGFR, patients with T790M mutation had median progression free survival (PFS) and overall survival (OS) as 9.6 months and 12.6 months, respectively; whereas the median PFS and OS of c-MET amplified patients was 4.1 months and 8.0 months, respectively. These results suggest that EGFR T790M mutation and c-MET amplification can occur in TKI-resistant NSCLC with wild-type EGFR, and these genetic defects might be related to different survival outcome. c-MET amplification in TKI-naive or -resistant patients might share similarities in clinicopathologic features.
C1 [Chen, Hua-Jun] Sun Yat-Sen University, Cancer CenterGuangzhou, China.
[Mok, S Tony] Chinese University of Hong Kong, Department of Clinical Oncology, Shatin, New TerritoriesHong Kong, Hong Kong.
[Chen, Zhi-Hong] Guangdong General Hospital, Guangdong Lung Cancer Institute, 106 Zhongshan Er Road, 510080 Guangzhou, Guangdong, China.
[Guo, Ai-Lin] Guangdong Academy of Medical Sciences, Department of BiochipGuangzhou, China.
[Zhang, Xu-Chao] Guangdong Academy of Medical Sciences, Department of BiochipGuangzhou, China.
[Su, Jian] Guangdong General Hospital, Guangdong Lung Cancer Institute, 106 Zhongshan Er Road, 510080 Guangzhou, Guangdong, China.
[Wu, Yi-Long] Guangdong General Hospital, Guangdong Lung Cancer Institute, 106 Zhongshan Er Road, 510080 Guangzhou, Guangdong, China.
RP Wu, YL (reprint author), Guangdong General Hospital, Guangdong Lung Cancer Institute, 510080 Guangzhou, China.
EM syylwu@live.cn
CR Pao W, Miller VA, Politi KA et al, 2005, Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2:e73
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Whitcombe D, Theaker J, Guy SP et al, 1999, Detection of PCR products using self-probing amplicons and fluorescence. Nat Biotechnol 17:804–807
Bean J, Brennan C, Shih JY et al, 2007, MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104:20932–20937
Inukai M, Toyooka S, Ito S et al, 2006, Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 66:7854–7858
Shih JY, Gow CH, Yang PC, 2005, EGFR mutation conferring primary resistance to gefitinib in non-small-cell lung cancer. N Engl J Med 353(2):207–208
Toyooka S, Kiura K, Mitsudomi T, 2005, EGFR mutation and response of lung cancer to gefitinib. N Engl J Med 352(20):2136 author reply 2136
Bell DW, Gore I, Okimoto RA et al, 2005, Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 37(12):1315–1316
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 651
EP 658
DI 10.1007/s12253-009-9167-8
PG 8
ER
PT J
AU Carlos-Bregni, R
Vidaurre, CE
Netto, CA
Leon, EJ
Almeida, PO
AF Carlos-Bregni, Roman
Vidaurre, C Elisa
Netto, Carolina Ana
Leon, E Jorge
Almeida, P Oslei
TI Primary Intraosseous Adenoid Cystic Carcinoma of the Mandible: Histopathological and Immunohistochemical Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Adenoid cystic carcinoma; Intraosseous; Mandible; Immunohistochemistry
ID Adenoid cystic carcinoma; Intraosseous; Mandible; Immunohistochemistry
AB Primary intraosseous salivary gland tumors of the mandible are rare, with mucopidermoid carcinoma being the most frequent, followed by adenoid cystic carcinoma (ACC). We present a case of a central ACC involving the mandible of a 46-year-old man. He presented an indurated swelling on the vestibular aspect of the left mandibular body and ipsilateral paraesthesia of the lower lip. A panoramic radiography revealed a large radiolucent area, with irregular margins, involving the body and ramus of the left mandible, and CT scan confirmed that the lesion was confined within the mandibular bone. The histopathological features were of an ACC. CT scan also revealed multiple nodular lesions in both lungs suggestive of metastases. The patient was surgically treated by hemimandibulectomy. The patient is well with no evidences of recurrences in the mandible. The present case shows that the clinical and immunohistochemical profile of primary intraosseous ACC is similar to what is found in ACC involving the salivary glands.
C1 [Carlos-Bregni, Roman] Centro Clinico de Cabeza y Cuello, 6 ave. 7-39 zona 10, ed. Las Brisas of. 501,, 01010 Ciudad de Guatemala, Guatemala.
[Vidaurre, C Elisa] Centro Clinico de Cabeza y Cuello, 6 ave. 7-39 zona 10, ed. Las Brisas of. 501,, 01010 Ciudad de Guatemala, Guatemala.
[Netto, Carolina Ana] Centro Clinico de Cabeza y Cuello, 6 ave. 7-39 zona 10, ed. Las Brisas of. 501,, 01010 Ciudad de Guatemala, Guatemala.
[Leon, E Jorge] State University of Campinas, School of Dentistry, Department of Oral Diagnosis, Av. Limeira 901, Caixa Postal 52, 13414-903 Piracicaba, Brazil.
[Almeida, P Oslei] State University of Campinas, School of Dentistry, Department of Oral Diagnosis, Av. Limeira 901, Caixa Postal 52, 13414-903 Piracicaba, Brazil.
RP Leon, EJ (reprint author), State University of Campinas, School of Dentistry, Department of Oral Diagnosis, 13414-903 Piracicaba, Brazil.
EM jorgeesquiche@yahoo.com.br
CR Bumstead WD, 1955, Cylindroma of the mandible. Oral Surg 8:546
Brookstone MS, Huvos AG, 1992, Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature. J Oral Maxillofac Surg 50:229– 236
Favia G, Maiorano E, Orsini G et al, 2000, Central, intraosseous, adenoid cystic carcinoma of the mandible: report of a case with periapical involvement. J Endod 12:760–763
Martinez-Madrigal F, Pineda-Daboin K, Casiraghi O et al, 2000, Salivary gland tumors of the mandible. Ann Diagn Pathol 4:347– 353
Capodiferro S, Scully C, Macaita MG et al, 2005, Bilateral intraosseous adenoid cystic carcinoma of the mandible: report of a case with lung metastases at first clinical presentation. Oral Dis 11:109–12
Al-Sukhun J, Lindqvist C, Hietanen J et al, 2006, Central adenoid cystic carcinoma of the mandible: case report and literature review of 16 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:304–308
Garcia de Marcos JA, Calderon-Polanco J, Poblet E et al, 2008, Primary adenoid cystic carcinoma of the mandible: case report and review of the literature. J Oral Maxillofac Surg 66:2609–2615
Mahomed F, Altini M, Meer S, et al, 2009, Central adenoid cystic carcinoma of the mandible with odontogenic features: Report of a case. Head Neck. Feb 2. [Epub ahead of print]
Li Y, Li LJ, Huang J et al, 2008, Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases. J Oral Maxillofac Surg 66:2247–2253
Ojha J, Bhattacharyya I, Islam MN et al, 2007, Intraosseous pleomorphic adenoma of the mandible: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:21–26
Chen JC, Gnepp DR, Bedrossian CW, 1988, Adenoid cystic carcinoma of the salivary glands: an immunohistochemical analysis. Oral Surg Oral Med Oral Pathol 65:316–326
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Foschini MP, Gaiba A, Cocchi R et al, 2005, p63 expression in salivary gland tumors: role of DeltaNp73L in neoplastic transformation. Int J Surg Pathol 13:329–335
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Bergman R, Lichtig C, Moscona RA et al, 1991, A comparative immunohistochemical study of adenoid cystic carcinoma of the skin and salivary glands. Am J Dermatopathol 13:162–168
Moran CA, Suster S, Koss MN, 1994, Primary adenoid cystic carcinoma of the lung. A clinicopathologic and immunohistochemical study of 16 cases. Cancer 73:1390–1397
Luo XL, Sun MY, Lu CT et al, 2006, The role of Schwann cell differentiation in perineural invasion of adenoid cystic and mucoepidermoid carcinoma of the salivary glands. Int J Oral Maxillofac Surg 35:733–739
Daa T, Kaku N, Kashima K et al, 2005, Expression of betacatenin, E-cadherin and cyclin D1 in adenoid cystic carcinoma of the salivary gland. J Exp Clin Cancer Res 24:83–87
Edwards PC, Bhuiya T, Kelsch RD, 2003, C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:586–593
Carlinfante G, Lazzaretti M, Ferrari S et al, 2005, P53, bcl-2 and Ki-67 expression in adenoid cystic carcinoma of the palate. A clinico-pathologic study of 21 cases with long-term follow-up. Pathol Res Pract 200:791–799
Vargas PA, Cheng Y, Barrett AWet al, 2008, Expression of Mcm- 2, Ki-67 and geminin in benign and malignant salivary gland tumours. J Oral Pathol Med 37:309–318
Woo VL, Bhuiya T, Kelsch R, 2006, Assessment of CD43 expression in adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, and monomorphic adenomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:495–500
Soares AB, Ponchio L, Juliano PB et al, 2007, Lymphatic vascular density and lymphangiogenesis during tumour progression of carcinoma ex pleomorphic adenoma. J Clin Pathol 60:995–1000
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 659
EP 664
DI 10.1007/s12253-009-9168-7
PG 6
ER
PT J
AU Kadota, K
Haba, R
Kushida, Y
Katsuki, N
Hayashi, T
Miyai, Y
Bando, K
Taoka, R
Kakehi, Y
AF Kadota, Kyuichi
Haba, Reiji
Kushida, Yoshio
Katsuki, Naomi
Hayashi, Toshitetsu
Miyai, Yumi
Bando, Kenji
Taoka, Rikiya
Kakehi, Yoshiyuki
TI Adult Extrarenal Wilms’ Tumor Mimicking Mixed Epithelial and Stromal Tumor in the Retroperitoneum: A Case Report with Immunohistochemical Study and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Adult; Extrarenal; Retroperitoneum; Mixed epithelial and stromal tumor; Wilms’ tumor
ID Adult; Extrarenal; Retroperitoneum; Mixed epithelial and stromal tumor; Wilms’ tumor
AB We report an extremely rare case of adult extrarenal Wilms’ tumor (WT) in a 52-year-old woman who presented with fever and abdominal distension. Computed tomography revealed a well-defined mass lesion measuring 15.0 cm in the right retroperitoneum and that was in contact with the right kidney. The mass and kidney were surgically removed. Grossly, the mass was well-defined, measuring 16.3×11.0×9.8 cm, and appearing grayish-white in color. The border between the mass and the kidney was welldefined. Histologically, the tumor showed a triphasic pattern consisting of stromal, epithelial and blastemal components. The stromal component was predominant in the tumor and consisted both of spindle cells and smooth muscle cells. The epithelial component showed a mature glandular structure. Immunohistochemically, the stromal component was positive for vimentin, smooth muscle actin and desmin. The blastemal component was positive for vimentin, while the epithelial component was positive for cytokeratin (CK) 18, CK7 and vimentin. WT-1 was negative in the all three components, and the Ki-67 proliferation index was low. The postoperative histopathological diagnosis indicated extrarenal WT arising in the retroperitoneum. Although not treated by either chemotherapy or radiation therapy, she was free from disease recurrence for 30 months after surgery. To the best of our knowledge, this report is only the fourth case of adult extrarenal WT arising in the retroperitoneum. Furthermore, the present case showed predominant smooth muscle differentiation and a mature glandular structure, mimicking a mixed epithelial and stromal tumor.
C1 [Kadota, Kyuichi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Haba, Reiji] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Kushida, Yoshio] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Katsuki, Naomi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Hayashi, Toshitetsu] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Miyai, Yumi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Bando, Kenji] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Taoka, Rikiya] Kagawa University, Faculty of Medicine, Department of UrologyKagawa, Japan.
[Kakehi, Yoshiyuki] Kagawa University, Faculty of Medicine, Department of UrologyKagawa, Japan.
RP Kadota, K (reprint author), Kagawa University, University Hospital, Department of Diagnostic Pathology, 761-0793 Kagawa, Japan.
EM qichi@med.kagawa-u.ac.jp
CR Terenziani M, Spreafico F, Collini P et al, 2004, Adult Wilms’ tumor: A monoinstitutional experience and a review of the literature. Cancer 101:289–293
Muc RS, Grayson W, Grobbelaar JJ, 2001, Adult extrarenal Wilms tumor occurring in the uterus. Arch Pathol LabMed 125:1081–1083
Isaac MA, Vijayalakshmi S, Madhu CS et al, 2000, Pure cystic WT of the ovary with a review of extrarenal Wilms’ tumors. Hum Pathol 31:761–764
Koretz MJ, Wang S, Klein FA et al, 1987, Extrarenal adult Wilms’ tumor. Cancer 60:2484–2488
Fukutomi Y, Shibuya C, Yamamoto S et al, 1988, Extrarenal Wilms’ tumor in the adult patient. A case report and review of the world literature. Am J Clin Pathol 90:618–622
Ratnam GV, Abu-Eshy S, Morad N et al, 2006, Adult extrarenal Wilms’ tumour: A case report and review of literature. West Afr J Med 25:75–78
Gillis AJ, Oosterhuis JW, Schipper ME et al, 1994, Origin and biology of a testicular Wilms’ tumor. Genes Chromosomes Cancer 11:126–135
Adsay NV, Eble JN, Srigley JR et al, 2000, Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 24:958–970
Ghanem MA, Van der Kwast TH, Den Hollander JC et al, 2000, Expression and prognostic value of Wilms’ tumor 1 and early growth response 1 proteins in WT. Clin Cancer Res 6:4265–4271
Vasei M, Moch H, Mousavi A et al, 2008, Immunohistochemical profiling of Wilms tumor: a tissue microarray study. Appl Immunohistochem Mol Morphol 16:128–134
Roberts DJ, Haber D, Sklar J et al, 1993, Extrarenal Wilms’ tumors. A study of their relationship with classical renal Wilms’ tumor using expression of WT-1 as a molecular marker. Lab Invest 68:528–536
Reinhard H, Aliani S, Ruebe C et al, 2004, Wilms’ tumor in adults: Results of the Society of Pediatric Oncology, SIOP, 93– 01/Society for Pediatric Oncology and Hematology, GPOH, Study. J Clin Oncol 22:4500–4506
Coppes MJ, Wilson PC, Weitzman S, 1991, Extrarenal Wilms’ tumor: staging, treatment, and prognosis. J Clin Oncol 9:167–174
Ghanem MA, Van der Kwast TH, Sudaryo MK et al, 2004, MIB-1, KI-67, proliferation index and cyclin-dependent kinase inhibitor p27(Kip1, protein expression in nephroblastoma. Clin Cancer Res 10:591–597
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 665
EP 669
DI 10.1007/s12253-009-9169-6
PG 5
ER
PT J
AU Chua, CT
Yao, P
Akther, J
Young, L
Bao, Sh
Samaraweera, U
Yan, DT
Morris, LD
AF Chua, C Terence
Yao, Peng
Akther, Javed
Young, Lawrence
Bao, Shisan
Samaraweera, Ushma
Yan, D Tristan
Morris, L David
TI Differential Expression of Ki-67 and Sex Steroid Hormone Receptors Between Genders in Peritoneal Mesothelioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mesothelioma; Ki-67 antigen; Estrogen receptor; Progesterone receptor; Androgen receptor; Cytoreductive surgery
ID Mesothelioma; Ki-67 antigen; Estrogen receptor; Progesterone receptor; Androgen receptor; Cytoreductive surgery
AB Gender influence on survival in mesothelioma has been observed in several large clinical series. However, this gender effect has not been investigated. Female patients often have less aggressive tumors and survive longer. However, few studies in the literature have explained the molecular basis of this finding. Understanding this difference at a molecular level may offer the hope of improving survival via hormonal manipulation.We investigate the expression of Ki-67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that characterize this gender difference. Positive expression of markers was observed in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of markers between gender showed a higher Ki-67 in males (M=1.3%, F=0.6%), higher estrogen receptor in females (M=0.6%, F=1.7%) and higher progesterone receptor in females (M=1.0%, F=1.4%). Twenty patients were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence of sex steroid receptors in peritoneal mesothelioma. Once the exact functional effects of these receptors are understood, the use of established therapeutic options that are clinically available to target the sex steroid pathway may become a reality.
C1 [Chua, C Terence] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
[Yao, Peng] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
[Akther, Javed] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
[Young, Lawrence] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
[Bao, Shisan] University of Sydney, School of Medical Sciences and Bosch Institute, Discipline of Pathology, NSW 2006 Sydney, Sydney, Australia.
[Samaraweera, Ushma] Prince of Wales Hospital, Department of Pathology, NSW 2031 Randwick, Sydney, Australia.
[Yan, D Tristan] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
[Morris, L David] St George Hospital, NSW 2217 Kogarah, Sydney, Australia.
RP Morris, LD (reprint author), St George Hospital, NSW 2217 Kogarah, Australia.
EM david.morris@unsw.edu.au
CR Boffetta P, 2007, Epidemiology of peritoneal mesothelioma: a review. Ann. Oncol. 18:985–90
RobinsonBW, Lake RA(2005, Advances in malignantmesothelioma. N Engl J Med. 353:1591–603
Sugarbaker PH, Welch LS, Mohamed F, Glehen OA, 2003, Review of peritoneal mesothelioma at theWashington Cancer Institute. Surg Oncol Clin N Am. 12:605–621
Acherman YI, Welch LS, Bromley CM, Sugarbaker PH, 2003, Clinical presentation of peritoneal mesothelioma. Tumori 89(3):269–73
Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O et al, 2008, Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma, MPM). Ann. Oncol. 19(2):370–3
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P et al, 2003, Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–44
Janne PA, Wozniak AJ, Belani CP, Keohan M-L, Ross HJ, Polikoff JA et al, 2005, Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer 7(1):40–6
Yan TD, Welch L, Black D, Sugarbaker PH, 2007, A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann. Oncol. 18(5):827–34
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Mineo TC, Ambrogi V, Pompeo E, Baldi A, Stella F, Aurea P et al, 2008, The value of occult disease in resection margin and lymph node after extrapleural pneumonectomy formalignant mesothelioma. Ann Thorac Surg 85(5):1740–6
Edwards JG, Stewart DJ, Martin-Ucar A, Muller S, Richards C, Waller DA, 2006, The pattern of lymph node involvement influences outcome after extrapleural pneumonectomy for malignant mesothelioma. J Thorac Cardiovasc Surg 131(5):981–7
Yan TD, Yoo D, Sugarbaker PH, 2006, Significance of lymph node metastasis in patients with diffuse malignant peritoneal mesothelioma. Eur. J. Surg. Oncol. 32(9):948–53
Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G, 1998, Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol 16(1):145–52
Adams VI, Unni KK, Muhm JR, Jett JR, Ilstrup DM, Bernatz PE, 1986, Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 cases. Cancer 58(7):1540–51
Metintas M, Metintas S, Ucgun I, Gibbs AR, Harmanci E, Alatas F et al, 2001, Prognostic factors in diffuse malignant pleural mesothelioma: effects of pretreatment clinical and laboratory characteristics. Respir. Med. 95(10):829–35
Yan TD, Popa E, Brun EA, Cerruto CA, Sugarbaker PH, 2006, Sex difference in diffuse malignant peritoneal mesothelioma. Br. J. Surg. 93(12):1536–42
Antman KH, Blum RH, Greenberger JS, Flowerdew G, Skarin AT, Canellos GP, 1980, Multimodality therapy for malignant mesothelioma based on a study of natural history. Am. J. Med. 68, 3):356–62
Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M et al, 2008, Extrapleural pneumonectomy versus pleurectomy/ decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. Journal of Thoracic & Cardiovascular Surgery 135(3):620–6
Neumann V, Rutten A, Scharmach M, Muller KM, Fischer M, 2004, Factors influencing long-term survival in mesothelioma patients–results of the German mesothelioma register. International Archives of Occupational & Environmental Health 77(3):191–9
Rusch VW, Venkatraman ES, 1999, Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Ann. Thorac. Surg. 68(5):1799–804
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Garcia-Carbonero R, Paz-Ares L, 2006, Systemic chemotherapy in the management of malignant peritoneal mesothelioma. Eur. J. Surg. Oncol. 32(6):676–81
Thomas Scholzen JG, 2000, The Ki-67 protein: From the known and the unknown. J Cell Physiol 182(3):311–22
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 671
EP 678
DI 10.1007/s12253-009-9170-0
PG 8
ER
PT J
AU Lu, M
Ma, J
Xue, W
Cheng, Ch
Wang, Y
Zhao, Y
Ke, Q
Liu, H
Liu, Y
Li, P
Cui, X
He, S
Shen, A
AF Lu, Mudan
Ma, Jianbo
Xue, Wenqun
Cheng, Chun
Wang, You
Zhao, Yueming
Ke, Qing
Liu, Haiou
Liu, Yonghua
Li, Peng
Cui, Xiaopeng
He, Song
Shen, Aiguo
TI The Expression and Prognosis of FOXO3a and Skp2 in Human Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma; FOXO protein FOXO3a; S-phase kinase protein (Skp2); Huh7; Immunohistochemistry (IHC); Prognosis
ID Human hepatocellular carcinoma; FOXO protein FOXO3a; S-phase kinase protein (Skp2); Huh7; Immunohistochemistry (IHC); Prognosis
AB The forkhead box proteins (FOXO proteins) comprise a large family of functionally diverse transcription factors involved in cellular proliferation, transformation, differentiation and longevity. Recently, ubiquitination and proteasome degradation of FOXO3a have been reported. In this study, we investigated the role of FOXO3a and Skp2 in human hepatocellular carcinoma progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 91 specimens. Furthermore in vitro, western-blot analysis and protein stabilization studies were used to study the relationship between FOXO3a and Skp2. We found that the expression of FOXO3a was negatively related with Skp2 expression (r=−0.583; p<0.05) and FOXO3a expression correlated significantly with histological grade (p=0.000), cirrhosis (p=0.015), and tumor size (p=0.043) while Skp2 expression correlated significantly with histological grade (p=0.000) and tumor size (p=0.005). Kaplan-Meier analysis revealed that survival curves of low versus high expressers of FOXO3a and Skp2 showed a highly significant separation in HCC (p<0.01). Our results suggested that FOXO3a and Skp2 may be considered to be important prognosis in human hepatocellular carcinoma. In vitro studies suggested that the degradation of FOXO3a may dependent on the expression of Skp2 in the proliferated Huh7 cells.
C1 [Lu, Mudan] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Ma, Jianbo] Affiliated Hospital of Nantong University, Department of Surgery, 226001 Nantong, China.
[Xue, Wenqun] Wuxi Maternal and Child Health Hospital, 214002 Wuxi, China.
[Cheng, Chun] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Wang, You] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Zhao, Yueming] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Ke, Qing] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Liu, Haiou] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Liu, Yonghua] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Li, Peng] Affiliated Hospital of Nantong University, Department of Surgery, 226001 Nantong, China.
[Cui, Xiaopeng] Affiliated Hospital of Nantong University, Department of Surgery, 226001 Nantong, China.
[He, Song] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Shen, Aiguo] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 19 Qi-xiu Road, 226001 Nantong, Jiangsu, China.
RP Shen, A (reprint author), Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, China.
EM Shen_aiguo@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 679
EP 687
DI 10.1007/s12253-009-9171-z
PG 9
ER
PT J
AU Nagy, Zs
Turcsik, V
Blasko, Gy
AF Nagy, Zsuzsanna
Turcsik, Vera
Blasko, Gyorgy
TI The Effect of LMWH (Nadroparin) on Tumor Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LMWH. Nadroparin; Tumor progression; Survival
ID LMWH. Nadroparin; Tumor progression; Survival
AB Recent clinical studies on patients with malignancies, who were treated with UHF and LMWHs raised the possibility, that these agents may possess an inhibitory effect on tumor progression. Further studies supported that this effect is independent from the anticoagulant and antithrombotic action. In this retrospective study oncological patients with an increased risk for thromboembolism were choosen, who received prophylactic treatment with an LMWH (nadroparin) at least for 6 months. Comparing with the control group, in some subgroups (T3 and T4, as well as M1) the LMWH-treated patients showed a significantly increased survival.
C1 [Nagy, Zsuzsanna] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Turcsik, Vera] Governmental Health Center, Department Anaesthesiology and Intensive CareBudapest, Hungary.
[Blasko, Gyorgy] University of Debrecen, Department of Pharmacology and PharmacotherapyDebrecen, Hungary.
RP Nagy, Zs (reprint author), St. Imre Hospital, Department Clinical Oncology, 1116 Budapest, Hungary.
EM zsulacz@chello.hu
CR von Delius S, Ayvaz M, Wagenpfeil S et al, 2007, Effect of lowmolecular- weight heparin on survival in patients with advanced pancreatic adenocarcinoma. Thromb Haemost 98:434–439
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Casu B, Vlodavsky I, Sanderson RD, 2009, Pathophysiol Haemost Thromb 2007-08: 36, 195–203,, DOI 10.1159/000175157
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 689
EP 692
DI 10.1007/s12253-009-9204-7
PG 4
ER
PT J
AU Ding, W
Ju, Sh
Jiang, Sh
Zhu, L
Wang, Y
Wang, H
AF Ding, Weifeng
Ju, Shaoqing
Jiang, Shengyang
Zhu, Li
Wang, Yueguo
Wang, Huimin
TI Reduced APRIL Expression Induces Cellular Senescence via a HSPG-Dependent Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE A proliferation-inducing ligand; Cellular senescence; Short hairpin RNA; Heparan sulfate proteoglycans
ID A proliferation-inducing ligand; Cellular senescence; Short hairpin RNA; Heparan sulfate proteoglycans
AB APRIL, a member of the TNF superfamily, can induce cell proliferation and is overexpressed in most tumor tissues or cells. Nevertheless, it is still unknown about the effect of decreased levels of APRIL expression on tumor cells. In this study, we analyzed APRIL and HSPG expression in the colon carcinoma cell line, SW480 by Western blot and RT-PCR. And the up-regulation of APRIL and HSPG expression was found in SW480. We also observed that knockdown of APRIL levels in SW480, prominently reversed cell proliferation and partially resulted in senescence phenotypes. Furthermore, cellular senescence due to a decreased level of APRIL expression was associated with engagement of HSPG. Thus, our results suggest that low levels of APRIL play an essential role in cellular senescence via a HSPG-dependent signaling pathway in SW480.
C1 [Ding, Weifeng] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, No.20, Road XisiNantong, China.
[Ju, Shaoqing] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, No.20, Road XisiNantong, China.
[Jiang, Shengyang] Nantong University, Department of Public HealthNantong, China.
[Zhu, Li] Nantong University, Jiangsu Province Key Laboratory of NeuroregenerationNantong, China.
[Wang, Yueguo] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, No.20, Road XisiNantong, China.
[Wang, Huimin] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, No.20, Road XisiNantong, China.
RP Wang, H (reprint author), Affiliated Hospital of Nantong University, Department of Laboratory Medicine, Nantong, China.
EM ntfyjyk@pub.nt.jsinfo.net
CR Bazzoni F, Beutler B, 1996, The tumor necrosis factor ligand and receptor families. N Engl J Med 334:1717–1725
Gaur U, Aggarwal BB, 2003, Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol 66:1403–1408
Hahne M, Kataoka T, Schroter M, Hofmann K, Irmler M, Bodmer JL, Schneider P et al, 1998, APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med 188:1185–1190
Mackay F, Schneider P, Rennert P, Browning J, 2003, BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol 21:231–264
Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl Wet al, 2002, BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J Immunol 169:4314–4321
Nishio M, Endo T, Tsukada N, Ohata J, Kitada S, Reed JC, Zvaifler NJ, Kipps TJ, 2005, Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF- 1alpha. Blood 106:1012–1020
Mongini PK, Inman JK, Han H, Fattah RJ, Abramson SB, Attur M, 2006, APRIL and BAFF promote increased viability of replicating human B2 cells via mechanism involving cyclooxygenase 2. J Immunol 176:6736–6751
Tangye SG, Bryant VL, Cuss AK, Good KL, 2006, BAFF, APRIL and human B cell disorders. Semin Immunol 18:305–317
Endo T, Nishio M, Enzler T, Cottam HB, Fukuda T, James DF, Karin M, Kipps TJ, 2006, BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway. Blood 109:703–710
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Dillon SR, Gross JA, Ansell SM, Novak AJ, 2006, An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov 5:235–246
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Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, Holler N et al, 2000, A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Expt Med 192:1677–1684
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Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP, 2005, Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation. Cell Death Differ 12:637–648
Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F et al, 2005, Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med 201:1375–1383
Lopez-Fraga M, Fernandez R, Albar JP, Hahne M, 2001, Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep 2:945–951
Wallweber HJ, Compaan DM, Starovasnik MA, Hymowitz SG, 2004, The crystal structure of a proliferation-inducing ligand, APRIL. J Mol Biol 343:283–290
Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, Olsson C et al, 2004, APRIL-deficient mice have normal immune system development. Mol Cell Biol 24:997–1006
Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M, 2001, APRIL, a new member of the tumor necrosis factor family, modulates death ligand—induced apoptosis. Cell Death Differ 8:403–410
Ben-Porath I, Weinberg RA, 2005, The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37:961–976
Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E et al, 2007, Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 109:729–739
Schwaller J, Schneider P, Mhawech-Fauceglia P, McKee T, Myit S, Matthes T et al, 2007, Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B cell lymphoma aggressiveness. Blood 109:331–338
Wagner M, Hampel B, Bernhard D, Hala M, Zwerschke W, Jansen- Durr P, 2001, Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis. Exp Gerontol 36:1327–1347
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 693
EP 701
DI 10.1007/s12253-009-9172-y
PG 9
ER
PT J
AU Xu, P
Yu, Sh
Jiang, R
Kang, Ch
Wang, G
Jiang, H
Pu, P
AF Xu, Peng
Yu, Shizhu
Jiang, Rongcai
Kang, Chunsheng
Wang, Guangxiu
Jiang, Hao
Pu, Peiyu
TI Differential Expression of Notch Family Members in Astrocytomas and Medulloblastomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Astrocytomas; Differential expression; Medulloblastomas; Notch family members
ID Astrocytomas; Differential expression; Medulloblastomas; Notch family members
AB Notch signaling pathway plays an integral role in determining cell fates in development. Growing evidence demonstrates that Notch signaling pathway has versatile effects in tumorigenesis depending on the tumor type, grade and stage. Notch signaling pathway is deregulated in some brain tumors. To examine the differential expression of Notch family members (Notch1, 2, 3, 4) in human astrocytomas and medulloblastomas, and to evaluate their roles in the development of both tumor types. Immunohistochemical staining and Western blot analysis were used to detect Notch1, 2, 3, 4 expression in tissue microarray and freshly resected tissue samples of normal brain, astrocytomas and medulloblastomas. Notch family members were not expressed or barely detectable in normal brain tissues. Notch1, 3, 4 were highly expressed but Notch2 was not expressed in astrocytomas. The percentage of immunopositive tumor cells and level of Notch1 expression was increased with tumor grade. In addition, overexpression of Notch2 was detected in medulloblastomas in contrast to low or no expression of Notch1, 3, 4. Differential expression of Notch1, 2, 3, 4 is detected in astrocytomas and medulloblastomas, that may be related to their different roles playing in the development of brain tumors.
C1 [Xu, Peng] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
[Yu, Shizhu] Tianjin Neurological Institute, Laboratory of NeuropathologyTianjin, China.
[Jiang, Rongcai] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
[Kang, Chunsheng] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
[Wang, Guangxiu] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
[Jiang, Hao] Henry Ford Hospital, Department of Neurology, 48202 Detroit, MI, USA.
[Pu, Peiyu] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
RP Pu, P (reprint author), Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
EM pupeiyu33@hotmail.com
CR Mizutani K, Yoon K, Dang L et al, 2007, Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449:351–355
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Fleming RJ, 1998, Structural conservation of Notch receptors and ligands. Semin Cell Dev Biol 9:599–607
Leong KG, Karsan A, 2006, Recent insights into the role of Notch signaling in tumorigenesis. Blood 107:2223–2233
Iso T, Kedes L, Hamamori Y, 2003, HES and HERP Families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:237–255
Lasky J, Wu H, 2005, Notch signaling, brain development, and human disease. Pediatr Res 57:104R–109R
Miele L, 2006, Notch signaling. Clin Cancer Res 12:1074–1079
Kovall RA, 2008, More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene 27:5099–5109
Hansson EM, Lendahl U, Chapman G, 2004, Notch signaling in development and disease. Semin Cancer Biol 14:320–328
Artavanis-Tsakonas S, Rand MD, Lake RJ, 1999, Notch signaling: cell fate control and signal integration in development. Science 284:770–776
Weng AP, Nam Y, Wolfe MS et al, 2003, Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol. 23:655–664
Weijzen S, Rizzo P, Braid M et al, 2002, Activation of Notch-1 signaling maintains the neoplastic phenotype in human Rastransformed cells. Nat Med 8:979–986
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McElhinny AS, Li JL, Wu L, 2008, Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways. Oncogene 27:5138–5147
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 703
EP 710
DI 10.1007/s12253-009-9173-x
PG 8
ER
PT J
AU Gole, B
Duran Alonso, BM
Dolenc, V
Lah, T
AF Gole, Boris
Duran Alonso, Beatriz Maria
Dolenc, Vincenc
Lah, Tamara
TI Post-Translational Regulation of Cathepsin B, but not of Other Cysteine Cathepsins, Contributes to Increased Glioblastoma Cell Invasiveness In Vitro
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Brain tumours; Cysteine cathepsins; Cystatins; Glioma; Invasion; Proteolysis; Stefins
ID Brain tumours; Cysteine cathepsins; Cystatins; Glioma; Invasion; Proteolysis; Stefins
AB Cells that migrate away from a central tumour into brain tissue are responsible for inefficient glioblastoma treatment. This migratory behaviour depends partially on lysosomal cysteine cathepsins. Reportedly, the expression of cathepsins B, L and S gradually increases in the progression from benign astrocytoma to the malignant glioblastoma, although their specific roles in glioma progression have not been revealed. The aim of this study was to clarify their specific contribution to glioblastoma cell invasion. The differences between the matrix invading cells and non-invading core cells from spheroids derived from glioblastoma cell culture and from glioblastoma patients’ biopsies, and embedded in type I collagen, have been studied at the mRNA, protein and cathepsin activity levels. Analyses of the two types of cells showed that the three cathepsins were up-regulated post-translationally, their specific activities increasing in the invading cells. The cystatin levels were also differentially altered, resulting in higher ratio of cathepsins B and L to stefin B in the invading cells. However, using specific synthetic inhibitors and silencing strategies revealed that only cathepsin B activity was involved in the invasion of glioblastoma cells, confirming previous notion of cathepsin B as tumour invasiveness biomarker. Our data support the concept of specific roles of cysteine cathepsins in cancer progression. Finally the study points out on the complexity of protease regulation and the need to include functional proteomics in the systems biology approaches to understand the processes associated with glioma invasion and progression.
C1 [Gole, Boris] National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Vecna pot 111, SI-1000 Ljubljana, Slovenia.
[Duran Alonso, Beatriz Maria] National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Vecna pot 111, SI-1000 Ljubljana, Slovenia.
[Dolenc, Vincenc] University Clinical Centre, Department of NeurosurgeryLjubljana, Slovenia.
[Lah, Tamara] National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Vecna pot 111, SI-1000 Ljubljana, Slovenia.
RP Gole, B (reprint author), National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, SI-1000 Ljubljana, Slovenia.
EM boris.gole@nib.si
CR Ohgaki H, Kleihues P, 2005, Epidemiology and etiology of gliomas. Acta Neuropathol 109(1):93–108
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Demuth T, Berens M, 2004, Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70(2):217–228
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Demuth T, Rennert JL, Hoelzinger DB et al, 2008, Glioma cells on the run- the migratory transcriptome of 10 human glioma cell lines. BMC Genomics 9:54
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Strojnik T, Kavalar R, Trinkaus M, Lah TT, 2005, Cathepsin L in glioma progression: comparison with cathepsin B. Cancer Detect Prev 29(5):448–455
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Flannery T, Gibson D, Mirakhur M et al, 2003, The clinical significance of cathepsin S expression in human astrocytomas. Am J Pathol 163(1):175–182
Flannery T, McQuaid S, McGoohan C et al, 2006, Cathepsin S expression: An independent prognostic factor in glioblastoma tumours-A pilot study. Int J Cancer 119(4):854–860
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 711
EP 723
DI 10.1007/s12253-009-9175-8
PG 13
ER
PT J
AU Bianchi, S
Caini, S
Cattani, GM
Vezzosi, V
Biancalani, M
Palli, D
AF Bianchi, Simonetta
Caini, Saverio
Cattani, Grazia Maria
Vezzosi, Vania
Biancalani, Mauro
Palli, Domenico
TI Diagnostic Concordance in Reporting Breast Needle Core Biopsies using the B Classification—A Panel in Italy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast; Non palpable lesions; Needle core biopsy; Reporting; Diagnostic concordance
ID Breast; Non palpable lesions; Needle core biopsy; Reporting; Diagnostic concordance
AB The widespread implementation of mammography screening has resulted in an increased frequency of needle core biopsies (NCB). The aim of this study was that of evaluating the diagnostic reproducibility on breast NCB, according to the B-classification, among several pathologists from different Italian regions. Fifty single slides of NCBs performed for non palpable breast lesions were selected to evaluate the diagnostic reproducibility, according to the B classification, among 31 pathologists from different Italian areas, involved in the pathologic diagnosis of screen-detected breast lesions. According to the study majority diagnosis (MD), 21 cases were classified as B2 (benign lesion), 23 B3 (lesion of uncertain malignant potential) and 6 B5 (malignant lesion). Overall, individual kappa coefficients in comparison to MD were good (mean 0.61, range 0.31–0.88). The level of inter-observer agreement, however, appeared lower in differentiating the two intermediate categories B2 and B3, thus potentially leading to over-treatment (false-positives: 26%) or under-treatment (false-negatives: 17%) of individual patients. Specific sub-types of B3 need an improvement of the diagnostic definition. A multidisciplinary approach and consultation with expert colleagues are recommended.
C1 [Bianchi, Simonetta] AOU Careggi, Department of Human Pathology and Oncology, AOU Careggi, Viale Morgagni, 50134 Florence, Italy.
[Caini, Saverio] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
[Cattani, Grazia Maria] Bellaria Hospital, Pathologic Anatomy UnitBologna, Italy.
[Vezzosi, Vania] AOU Careggi, Department of Human Pathology and Oncology, AOU Careggi, Viale Morgagni, 50134 Florence, Italy.
[Biancalani, Mauro] Empoli Hospital, Pathologic Anatomy UnitFlorence, Italy.
[Palli, Domenico] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
RP Bianchi, S (reprint author), AOU Careggi, Department of Human Pathology and Oncology, 50134 Florence, Italy.
EM simonetta.bianchi@unifi.it
CR El-Sayed ME, Rakka EA, Reed J et al, 2008, Audit of performance of needle core biopsy diagnoses of screen detected breast lesions. Eur J Cancer 44:2580–2586
NHSBSP Breast Screening Programme, 2001, Guidelines for Non-Operative Diagnostic Procedures and Reporting in Breast Cancer Screening. Sheffield: NHSBSP Pub. No.50
European Commission Working Group on Breast Screening Pathology, 2006, Quality assurance guidelines for pathology. In: Perry N, Broeders M, de Wolf C, Tornberg S, Holland R, von Karsa L, eds, European guidelines for quality assurance in breast cancer screening and diagnosis. Volume 6, 4th edn. Office for Official Publications of the European Communities, Luxemburg, pp 219–312
Pinder SE, Reis-Filho JS, 2007, Non-operative breast pathology. J Clin Pathol 60:1297–1299
Verkooijen HM, 2008, Needle core biopsy for screen detected breast lesions: time to raise the bar. Eur J. Cancer 44:2540–2541
Kumaroswamy V, Liston J, Shaaban AM, 2008, Vacuum assisted stereotactic guided mammotome biopsies in the management of screen detected microcalcifications: experience of a large breast screening centre. J Clin Pathol 61:766–769
Lazarus E, Mainiero MB, Schepps B et al, 2006, BI-RADS lexicon for US and mammography: interobserver variability and positive predictive value. Radiology 239:385–391
Schnitt SJ, Vincent-Salomon A, 2003, Columnar cell lesions of the breast. Adv Anat Pathol 10:113–124
Cohen J, 1960, A coefficient of agreement for nominal scales. Educational and Psychological Measurement 20:37–46
Landis JR, Koch GG, 1977, The measurement of observer agreement for categorical data. Biometrics 33:59–174
Bonk U, Gohla G, Sauer U et al, 2005, Grosse Ubereinstimmung Eergebnisse des ersten Mammographie-Screening-Projekts in Bremen aus histopathologischer Sicht. Deutsche Arzteblatt online, http://www.aerzteblatt.de/aufsaetze/0501)
Kluttig A, Trocchi P, Heinig A et al, 2007, Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization—design and objectives of the Diagnosis Optimisation Study, DIOS). BMC Cancer 7:100– 108
Collins LC, Connolly JL, Page DL et al, 2007, Diagnostic agreement in the evaluation of image-guided breast core needle biopsies. Am J Surg Pathol 28:126–131
Houssami N, Ciatto S, Bilous M et al, 2007, Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential, B3). Br J Cancer 96:1253–1257
Verkooijen HM, Peterse JL, Schipper MEI et al, 2003, Interobserver variability between general and expert pathologists during the histopathological assessment of large-core needle and open biopsies of non-palpable breast lesions. Eur J Cancer 39:2187– 2191
Lee AD, Denley HE, Pinder SE et al, 2003, Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy, B4, or lesion of uncertain malignant potential, B3). Histopathology 42:331–336
Dillon MF, McDermott EW, Hill AD et al, 2007, Predictive value of breast lesions of “Uncertain Malignant Potential” and “Suspicious for malignancy” determined by needle core biopsy. Ann Surg Oncol 14:704–711
Tan PH, Ho BCS, Selvarajan S et al, 2005, Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility? J Clin Pathol 58:705–709
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 725
EP 732
DI 10.1007/s12253-009-9176-7
PG 8
ER
PT J
AU Coufal, O
Pavlik, T
Fabian, P
Bori, R
Boross, G
Sejben, I
Maraz, R
Koca, J
Krejci, E
Horakova, I
Foltinova, V
Vrtelova, P
Chrenko, V
Tekle, EW
Rajtar, M
Svebis, M
Fait, V
Cserni, G
AF Coufal, Oldrich
Pavlik, Tomas
Fabian, Pavel
Bori, Rita
Boross, Gabor
Sejben, Istvan
Maraz, Robert
Koca, Jaroslav
Krejci, Eva
Horakova, Iva
Foltinova, Vendula
Vrtelova, Pavlina
Chrenko, Vojtech
Tekle, Eliza Wolde
Rajtar, Maria
Svebis, Mihaly
Fait, Vuk
Cserni, Gabor
TI Predicting Non-Sentinel Lymph Node Status After Positive Sentinel Biopsy in Breast Cancer: What Model Performs the Best in a Czech Population?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Lymphatic metastasis; Nomogram; Prediction; Sentinel lymph node biopsy; Tumor cells; Isolated
ID Breast cancer; Lymphatic metastasis; Nomogram; Prediction; Sentinel lymph node biopsy; Tumor cells; Isolated
AB Several models have previously been proposed to predict the probability of non-sentinel lymph node (NSLN) metastases after a positive sentinel lymph node (SLN) biopsy in breast cancer. The aim of this study was to assess the accuracy of two previously published nomograms (MSKCC, Stanford) and to develop an alternative model with the best predictive accuracy in a Czech population. In the basic population of 330 SLN-positive patients from the Czech Republic, the accuracy of the MSKCC and the Stanford nomogramswas tested by the area under the receiver operating characteristics curve (AUC). A new model (MOU nomogram) was proposed according to the results of multivariate analysis of relevant clinicopathologic variables. The new model was validated in an independent test population from Hungary (383 patients). In the basic population, six of 27 patients with isolated tumor cells (ITC) in the SLN harbored additional NSLN metastases. The AUCs of the MSKCC and Stanford nomograms were 0.68 and 0.66, respectively; for the MOU nomogram it reached 0.76. In the test population, the AUC of the MOU nomogram was similar to that of the basic population (0.74). The presence of only ITC in SLN does not preclude further nodal involvement. Additional variables are beneficial when considering the probability of NSLN metastases. In the basic population, the previously published nomograms (MSKCC and Stanford) showed only limited accuracy. The developed MOU nomogram proved more suitable for the basic population, such as for another independent population from a mid-European country.
C1 [Coufal, Oldrich] Masaryk Memorial Cancer Institute, Department of Surgical Oncology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Pavlik, Tomas] Masaryk University, Institute of Biostatistics and Analyses, Kamenice 126/3, 62500 Brno, Czech Republic.
[Fabian, Pavel] Masaryk Memorial Cancer Institute, Department of Pathology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38Kecskemet, Hungary.
[Boross, Gabor] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38Kecskemet, Hungary.
[Sejben, Istvan] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38Kecskemet, Hungary.
[Maraz, Robert] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38Kecskemet, Hungary.
[Koca, Jaroslav] ADDS&DSC International s.r.o, Jana Uhra 10, 60200 Brno, Czech Republic.
[Krejci, Eva] Masaryk Memorial Cancer Institute, Department of Pathology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Horakova, Iva] Masaryk Memorial Cancer Institute, Department of Pathology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Foltinova, Vendula] Masaryk Memorial Cancer Institute, Department of Surgical Oncology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Vrtelova, Pavlina] Masaryk Memorial Cancer Institute, Department of Surgical Oncology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Chrenko, Vojtech] Masaryk Memorial Cancer Institute, Department of Surgical Oncology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Tekle, Eliza Wolde] Bacs-Kiskun County Hospital, Department of Oncoradiology, Nyiri ut 38Kecskemet, Hungary.
[Rajtar, Maria] Bacs-Kiskun County Hospital, Department of Oncoradiology, Nyiri ut 38Kecskemet, Hungary.
[Svebis, Mihaly] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38Kecskemet, Hungary.
[Fait, Vuk] Masaryk Memorial Cancer Institute, Department of Surgical Oncology, Zluty kopec 7, 65653 Brno, Czech Republic.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38Kecskemet, Hungary.
RP Coufal, O (reprint author), Masaryk Memorial Cancer Institute, Department of Surgical Oncology, 65653 Brno, Czech Republic.
EM oldrich.coufal@gmail.com
CR Park J, Fey JV, Naik AM, Borgen PI, Van Zee KJ, Cody HS 3rd, 2007, A declining rate of completion axillary dissection in sentinel lymph node-positive breast cancer patients is associated with the use of a multivariate nomogram. Ann Surg 245:462–468
Hwang RF, Gonzalez-Angulo AM, Yi M et al, 2007, Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer 10:723–730
Van Zee KJ, Manasseh DM, Bevilacqua JL et al, 2003, A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patient with a positive sentinel node biopsy. Ann Surg Oncol 10:1140–1151
Degnim AC, Reynolds C, Pantvaidya G et al, 2005, Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram. Am J Surg 190:543–550
Cripe MH, Beran LC, Liang WC, Sickle-Santanello BJ, 2006, The likelihood of additional nodal disease following a positive sentinel lymph node biopsy in breast cancer patients: validation of a nomogram. Am J Surg 192:484–487
Smidt ML, Kuster DM, van der Wilt GJ, Thunnissen FB, Van Zee KJ, Strobbe LJ, 2005, Can the memorial Sloan-Kettering cancer center nomogram predict the likelihood of nonsentinel lymph node metastases in breast cancer patients in the Netherlands? Ann Surg Oncol 12:1066–1072
Soni NK, Carmalt HL, Gillett DJ, Spillane AJ, 2005, Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node positivity. Eur J Surg Oncol 31:958–964
Lambert LA, Ayers GD, Hwang RF et al, 2006, Validation of a breast cancer nomogram for predicting nonsentinel lymph node metastases after a positive sentinel node biopsy. Ann Surg Oncol 13:310–320
Ponzone R, Maggiorotto F, Mariani L et al, 2007, Comparison of two models for the prediction of nonsentinel node metastases in breast cancer. Am J Surg 193:686–692
Kocsis L, Svebis M, Boross G et al, 2004, Use and limitations of a nomogram predicting the likelihood of non-sentinel node involvement after a positive sentinel node biopsy in breast cancer patients. Am Surg 70:1019–1024
Zgajnar J, Perhavec A, Hocevar M et al, 2007, Low performance of the MSKCC nomogram in preoperatively ultrasonically negative axillary lymph node in breast cancer patients. J Surg Oncol 96:547–553
Alran S, De Rycke Y, Fourchotte V et al, 2007, Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy. Ann Surg Oncol 14:2195–2201
Pal A, Provenzano E, Duffy SW, Pinder SE, Purushotham AD, 2008, A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive. Br J Surg 95:302–309
Klar M, Jochmann A, Foeldi M et al, 2008, The MSKCC nomogram for prediction the likelihood of non-sentinel node involvement in a German breast cancer population. Breast Cancer Res Treat 112:523–531
Poirier E, Sideris L, Dube P, Drolet P, Meterissian SH, 2008, Analysis of clinical applicability of the breast cancer nomogram for positive sentinel lymph node: the canadian experience. Ann Surg Oncol 15:2562–2567
Kohrt HE, Olshen RA, Bermas HR et al, 2008, New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer 8:66
Lyman GH, Giuliano AE, Somerfield MR et al, 2005, American society of clinical oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720
Sobin LH, Wittekind Ch, eds,, 2002, TNM Classification of Malignant Tumors, 6th Edn. Wiley & Sons, New Jersey
Houvenaeghel G, Nos C, Mignotte H et al, 2006, Micrometastases in sentinel lymph node in a multicentric study: predictive factors of nonsentinel lymph node involvement–Groupe des Chirurgiens de la Federation des Centres de Lutte Contre le Cancer. J Clin Oncol 24:1814–1822
Cserni G, Rajtar M, Boross G et al, 2002, Comparison of vital dye-guided lymphatic mapping and dye plus gamma probe-guided sentinel node biopsy in breast cancer. World J Surg 26:592–597
Cserni G, 2002, Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 55:926–931
Memorial Sloan-Kettering Cancer Center. Breast cancer nomograms: additional nodal metastases. http://www.mskcc.org/mskcc/ html/15938.cfm. Citied 24 Feb 2009
Kohrt HE, Olshen RA, Jeffrey SS. Non-sentinel lymph node metastasis calculator. Available: https://www3-hrpdcc.stanford. edu/nsln-calculator/. Citied 24 Feb 2009
Hanley JA, McNeil BJ, 1982, The meaning and use of the area under the Receiver Operating Characteristic, ROC, curve. Radiology 143:29–36
Cserni G, Bianchi S, Vezzosi V et al, 2008, Sentinel lymph node biopsy in staging small, up to 15 mm, breast carcinomas. Results from a European multi-institutional study. Pathol Oncol Res 14:117–121
Turner RR, Weaver DL, Cserni G et al, 2008, Nodal stage classification for breast carcinoma: improving interobserver reproducibility through standardized histologic criteria and image-based training. J Clin Oncol 26:258–263
de Mascarel I, MacGrogan G, Debled M, Brouste V, Mauriac L, 2008, Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful? Cancer 112:1672–1678
Cserni G, Bianchi S, Vezzosi V et al, 2008, Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions. Eur J Cancer 44:2185–2191
Cserni G, 2007, Comparison of different validation studies on the use of the Memorial-Sloan Kettering cancer center nomogram predicting nonsentinel node involvement in sentinel node-positive breast cancer patients. Am J Surg 194:699–700
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2009
VL 15
IS 4
BP 733
EP 740
DI 10.1007/s12253-009-9177-6
PG 8
ER
PT J
AU Aktas, S
Celebiler, CA
Zadeoglulari, Z
Diniz, G
Kargi, A
Olgun, N
AF Aktas, Safiye
Celebiler, Cavusoglu Aydan
Zadeoglulari, Zeynep
Diniz, Gulden
Kargi, Aydanur
Olgun, Nur
TI Expression and Methylation Pattern of p16 in Neuroblastoma Tumorigenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroblastoma; p16; Methylation
ID Neuroblastoma; p16; Methylation
AB Understanding migration, population and differentiation of primordial neural crest cells will help in evolving biology of neuroblastoma. P16 is a tumour suppressor gene contributing in cell cycle arrest as cyclin dependent kinase inhibitor. Methylation is an important mechanism for silencing tumor suppressor genes. The aim of this study was to evaluate the role of p16 and its methylation pattern in neuroblastoma tumorigenesis. This study included 23 cases (11 male; 12 female) and 31 samples from archival paraffin embedded tissues. P16 was studied in 5 samples of normal adrenal medullar tissue, 5 samples of adrenal tissue including blastic rests, 5 samples of neuroblastoma in situ tissue and in 8 samples of neuroblastoma tissues primary and after chemotherapy in each group. The adrenal gland tissues were obtained from paediatric autopsy cases. Expression of p16 was searched by immunohistochemistry. Methylation specific PCR was used to detect the methylation rate of p16. The age range of autopsy cases was between 20 weeks of foetal age and 36 months of infant age. The mean age of neuroblastoma cases was 45 months. P16 expression was positive in normal adrenal tissues, in one of 5 samples of adrenal blastic rest tissue and in all of samples of after chemotherapy; while no expression was observed in neuroblastoma and neuroblastoma in situ tissues. P16 methylation was observed in samples of neuroblastoma in situ and primary neuroblastoma tissues. Our results suggest that p16 and its methylation seems to play role in neuroblastoma tumorigenesis and in the migration, population and differentiation of primordial neural crest cells. Inhibitors of DNA methylation may provide a useful tool for restoring p16 activity in neuroblastoma treatment.
C1 [Aktas, Safiye] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
[Celebiler, Cavusoglu Aydan] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
[Zadeoglulari, Zeynep] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
[Diniz, Gulden] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
[Kargi, Aydanur] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
[Olgun, Nur] Dokuz Eylul University, Institute of Oncology, 125/7 sokak Brickent A-3-3Bornova, Izmir, Turkey.
RP Aktas, S (reprint author), Dokuz Eylul University, Institute of Oncology, Bornova, Turkey.
EM safiyeaktas@yahoo.com
CR Michalowski MB, de Fraipont F, Plantaz D, Michelland S, Combaret V, Favrot MC, 2008, Methylation of tumor-suppressor genes in neuroblastoma: the RASSF1A gene is almost always methylated in primary tumors. Pediatr Blood Cancer 50(1):29–32
Bassi CL, Martelli L, Cipolotti R, Scrideli CA, Defavery R, Tone LG, 2004, Lack of evidence for mutations or deletions in the CDKN2A/p16 and CDKN2B/p15 genes of Brazilian neuroblastoma patients. Braz J Med Biol Res 37(11):1683–1687
Takita J, Hayashi Y, Nakajima T, Adachi J, Tanaka T, Yamaguchi N, Ogawa Y, Hanada R, Yamamoto K, Yokota J, 1998, The p16, CDKN2A, gene is involved in the growth of neuroblastoma cells and its expression is associated with prognosis of neuroblastoma patients. Oncogene 17(24):3137–3143
Omura-Minamisawa M, Diccianni MB, Chang RC, Batova A, Bridgeman LJ, Schiff J, Cohn SL, London WB, Yu AL, 2001, p16/p14(ARF, cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease. Clin Cancer Res 7(11):3481–3490
Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J, 2003, Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22, 16):4212–4222
Ohtani N, Yamakoshi K, Takahashi A, Hara E, 2004, The p16INK4a-RB pathway: molecular link between cellular senescence and tumor suppression. J Med Invest 51(3–4):146–153
Ebinger M, Senf L, Wachowski O, Scheurlen W, 2004, Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma. Pathol Oncol Res 10(1): 17–21
Ivanova TA, Golovina DA, Zavalishina LE, Volgareva GM, Katargin AN, Andreeva YY, Frank GA, Kisseljov FL, 2007, Kisseljova NP.Up-regulation of expression and lack of 5′ CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas. BMC Cancer 7:47
Attri J, Srinivasan R, Majumdar S, Radotra BD, Wig J, 2005, Alterations of tumor suppressor gene p16INK4a in pancreatic ductal carcinoma. BMC Gastroenterol 5:22
Liu Y, Lan Q, Siegfried JM, Luketich JD, Keohavong P, 2006, Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia 8(1):46–51
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 1
EP 6
DI 10.1007/s12253-009-9178-5
PG 6
ER
PT J
AU Noel, JCh
Fayt, I
Buxant, F
AF Noel, Jean-Christophe
Fayt, Isabelle
Buxant, Frederic
TI Proliferating Activity in Paget Disease of the Nipple
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Paget disease; Nipple; Breast; Proliferation; Ki-67; Double stain immunohistochemistry
ID Paget disease; Nipple; Breast; Proliferation; Ki-67; Double stain immunohistochemistry
AB Paget disease of the nipple is a rare disease characterized by the presence of malignant glandular cells within the squamous epithelium of the nipple. The most common hypothesis to explain the development of Paget disease is an intraepithelial epidermotropic migration of malignant epithelial cells originating from an underlying intraductal carcinoma. If the immunohistochemical properties of the Paget cells in the nipple have been extensively studied, their proliferating characteristics remain paradoxically poorly studied. In the present study we have investigated the proliferating activity of Paget cells in the nipple by using double stain immunohistochemistry with both Ki67 (a protein which is expressed in all active parts of the cell cycle) and cytokeratin 7 (a highly sensitive marker of Paget cells). Ten cases of Paget disease and in their associated intraductal carcinomas (n=10) and/or invasive carcinomas (n=4) were tested. The mean Ki67 index was in Paget disease (26%±10), in intraductal carcinomas (23%±8) and/or in invasive carcinomas (20%±8) (p>0,05). This is the first report to convincingly demonstrate by specific double stain immunohistochemistry that Paget disease and underlying intraductal carcinomas share a close proliferating activity.
C1 [Noel, Jean-Christophe] Free University of Brussels (ULB), Erasme Hospital, Departments of Pathology, 808 route de Lennik, 1070 Brussels, Belgium.
[Fayt, Isabelle] Free University of Brussels (ULB), Erasme Hospital, Departments of Pathology, 808 route de Lennik, 1070 Brussels, Belgium.
[Buxant, Frederic] Free University of Brussels (ULB), Erasme Hospital, Departments of GynecologyBrussels, Belgium.
RP Noel, JCh (reprint author), Free University of Brussels (ULB), Erasme Hospital, Departments of Pathology, 1070 Brussels, Belgium.
EM Jean-Christophe.Noel@erasme.ulb.ac.be
CR Eusebi V, Mai KT, Taranger-Charpin A, 2003, Tumours of the nipple. In: Tavassoli FA, Devilee P, eds, World Health Organization Classification of Tumours. Pathology & Genetics. Tumours of the Breast and Female Genital Organs. IARC, Lyon, pp 104– 106
Ellis IO, Elston CW, Poller DN, 1998, Paget’s disease of the nipple. In: Elston CW, Ellis IO, eds, The breast. Churchill Linvingstone, Edinburgh, pp 276–281
Rosen PP, 2001, Paget’s disease of the nipple. In: Rosen PP, ed, Rosen’s breast pathology. Lippincott Williams & Wilkins, Philadelphia, pp 565–579
Cohen I, Guarner J, DeRose PB, 1993, Mammary Paget’s disease and associated carcinoma. An immunohistochemical study. Arch Pathol Lab Med 117:291–294
Fu W, Mittel VK, Young SC, 2001, Paget disease of the breast: analysis of 41 patients. Am J Clin Oncol 24:397–400
Kothari AS, Beechey-Newman N, Hamed H et al, 2002, Paget disease of the nipple: a multifocal manifestation of higher-risk disease. Cancer 95:1–7
Schelfhout VRJ, Coene ED, Delaey B et al, 2000, Pathogenesis of Paget’s disease: epidermal heregulin-alpha motility factor and the HER receptor family. J Natl Cancer Inst 92:622–628
De Potter CR, Eeckhout I, Schelfhout AM et al, 1994, Keratinocyte induced chemotaxis in the pathogenesis of Paget’s disease of the breast. Histopathology 24:349–356
Marucci G, Betts C, Golouh R et al, 2002, Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description. Virchows Arch 441:117–123
Lammie GA, Barnes DM, Millis RR, Gullick WJ, 1989, An immunohistochemical study of the presence of c-erb-2 protein in Paget’s disease of the nipple. Histopathology 15:505–514
Keatings L, Sinclair J, Wright C et al, 1990, C-erb-2 oncoprotein expression in mammary and extrammary Paget’s disease. Histopathology 17:243–247
Ellis PE, Wong Te Fong LF, MPhil R et al, 2002, The role of p53 and Ki67 in Paget’s disease of the vulva and the breast. Gynecologic Oncology 86:150–156
Endl E, Gerdes J, 2000, The Ki-67 protein: fascinating forms of unknown function. Exp Cell Res 257:231–237
Noel JC, Fayt I, Fernandez-Aguilar S et al, 2006, Proliferating activity in columnar cells lesions of the breast. Virchows Arch 449:617–621
Heenen M, Thiriar S, Noel JC et al, 1998, Ki-67 immunostaining of normal human epidermis: comparison with 3H-thymidine labelling and PCNA immunostaining. Dermatology 197:123– 126
Elston CW, Ellis IO, 1991, Pathological prognostic factors in breast cancer. The value of histological grade in breast: experience from a large study with long-term follow-up. Histopathology 19:403–410
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 7
EP 10
DI 10.1007/s12253-009-9179-4
PG 4
ER
PT J
AU Sipos, F
Muzes, Gy
Galamb, O
Spisak, S
Krenacs, T
Toth, K
Tulassay, Zs
Molnar, B
AF Sipos, Ferenc
Muzes, Gyorgyi
Galamb, Orsolya
Spisak, Sandor
Krenacs, Tibor
Toth, Kinga
Tulassay, Zsolt
Molnar, Bela
TI The Possible Role of Isolated Lymphoid Follicles in Colonic Mucosal Repair
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Isolated lymphoid follicle; Colon; Mucosal repair; Epithelial stem cell; Myofibroblast; Follicular dendritic cell; Bone marrow; Mesenchymal-epithelial transition
ID Isolated lymphoid follicle; Colon; Mucosal repair; Epithelial stem cell; Myofibroblast; Follicular dendritic cell; Bone marrow; Mesenchymal-epithelial transition
AB The continuous reformation and rapid repair of the colonic mucosa is essential for avoiding the aggregation of pernicious mutations induced by bacterial, toxic, or mitogenic factors. Gut-associated lymphoid tissue is supposed to play a central role in the organization of the repair mechanisms. In inflammatory conditions, the number, the diameter and the density of isolated lymphoid follicles (ILFs) are increasing. They are involved not just in immune surveillance, but their presence is also indispensable in normal mucosal regeneration of the colon. The relation of ILFs to the components of mucosal renewal such as bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts or crypt formation has not been directly studied, and data about their putative organizer role are scattered in scientific literature. Whether they act as a regenerative pool containing stem cells in case of mucosal damage, or they are responsible only for the optimal cytokine milieu for the differentiation of immigrating stem cells is a question under debate. Our aim is to review the relation of ILFs to the different elements of colonic mucosal repair.
C1 [Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Muzes, Gyorgyi] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Spisak, Sandor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
RP Sipos, F (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM sipos.ferenc@freemail.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 11
EP 18
DI 10.1007/s12253-009-9181-x
PG 8
ER
PT J
AU Nemeth, J
Nemeth, Zs
Tatrai, P
Peter, I
Somoracz,
Szasz, MA
Kiss, A
Schaff, Zs
AF Nemeth, Julia
Nemeth, Zsuzsanna
Tatrai, Peter
Peter, Ilona
Somoracz, Aron
Szasz, Marcell Attila
Kiss, Andras
Schaff, Zsuzsa
TI High Expression of Claudin-1 Protein in Papillary Thyroid Tumor and its Regional Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Claudin-1; Lymph node metastasis; Papillary thyroid carcinoma; Tumor marker
ID Claudin-1; Lymph node metastasis; Papillary thyroid carcinoma; Tumor marker
AB Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of β-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by β-catenin in thyroid tumors. Based on these results, claudin-1 may be a useful tumor marker for PTC.
C1 [Nemeth, Julia] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Nemeth, Zsuzsanna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Tatrai, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Peter, Ilona] National Institute of Oncology, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Somoracz, Aron] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM schaff@korb2.sote.hu
CR Pacini F, Schlumberger M, Dralle H et al, 2006, European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154:787–803
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 19
EP 27
DI 10.1007/s12253-009-9182-9
PG 9
ER
PT J
AU Szendroi, A
Dinya, E
Kardos, M
Szasz, MA
Nemeth, Zs
Ats, K
Kiss, J
Antal, I
Romics, I
Szendroi, M
AF Szendroi, Attila
Dinya, Elek
Kardos, Magdolna
Szasz, Marcel Attila
Nemeth, Zsuzsanna
Ats, Katalin
Kiss, Janos
Antal, Imre
Romics, Imre
Szendroi, Miklos
TI Prognostic Factors and Survival of Renal Clear Cell Carcinoma Patients with Bone Metastases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone metastases; Fuhrman grade; Prognostic factors; Renal cell cancer; Surgical treatment; Survival analysis
ID Bone metastases; Fuhrman grade; Prognostic factors; Renal cell cancer; Surgical treatment; Survival analysis
AB In our retrospective study the pathological and clinical factors, influencing the survival of 65 renal clear cell carcinoma patients operated for bone metastasis between 1990 and 2008 were examined. Based on Kaplan-Meier curves age, gender, clinical symptoms, pathological fracture, progression to the soft tissues, localization and size of the metastasis, whether the occurrence of multiplex metastases is multiorganic or only located to the skeletal system and the stage and grade of primary renal cancer did not influence the survival. The survival significantly improved if the bone metastases were solitary, low Fuhrman grade, late onset; and radical surgery was performed. Based on Cox regression analysis, survival after bone surgery was influenced by the multiplicity and grade of metastasis and by the radicality of the surgery, whereas survival after nephrectomy was significantly influenced by onset time and grade of metastasis. When the solitary metastasis was radically removed, 75.0% of the patients survived the first, and 35.5% the fifth postoperative year. If the metastasis was multiple or the surgery was not radical, no patient survived the fifth year. This is the first report on the prognostic significance of the Fuhrman grade of bone metastasis of renal cell cancer. While the Fuhrman grade of the primary tumour did not influence the survival, the lower grade of metastasis was associated with a significant longer survival. Therefore in cases of solitary, operable, late onset metastases with low Fuhrman grade radical removal is recommended, since this way in 35.5% of cases 5 year survival can be expected.
C1 [Szendroi, Attila] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1082 Budapest, Hungary.
[Dinya, Elek] EGIS Pharmaceuticals PLC, Medical DepartmentBudapest, Hungary.
[Kardos, Magdolna] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szasz, Marcel Attila] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Nemeth, Zsuzsanna] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Ats, Katalin] National Institute for Rheumatology and PhysiotherapyBudapest, Hungary.
[Kiss, Janos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Antal, Imre] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Romics, Imre] Semmelweis University, Department of Urology, Ulloi ut 78/b, H-1082 Budapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
RP Szendroi, A (reprint author), Semmelweis University, Department of Urology, H-1082 Budapest, Hungary.
EM aszendroi@gmail.com
CR Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics, 2008. CA Cancer J Clin 58(2):71–96
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 29
EP 38
DI 10.1007/s12253-009-9184-7
PG 10
ER
PT J
AU Li, Z
Tu, J
Yu, Zl
Wu, Yd
Xu, Cm
Zhang, Sht
AF Li, Zhang
Tu, Jun
Yu, Zhong-lin
Wu, Yong-dong
Xu, Cai-min
Zhang, Shu-tian
TI Effects of the Inhibition of Cyclooxygenase-2 on Human Esophageal Cancer Cells: Inhibition of Cell Proliferation and Induction of Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma (ESCC); Cyclooxygenase-2 (COX-2); Acidum acetil salicylicum (aspirin); Cell proliferation; Apoptosis; Synergistic effect
ID Esophageal squamous cell carcinoma (ESCC); Cyclooxygenase-2 (COX-2); Acidum acetil salicylicum (aspirin); Cell proliferation; Apoptosis; Synergistic effect
AB Cyclooxygenase-2 (COX-2) has been shown to be upregulated in a variety of tumors so that COX-2 may be a potential target in the treatment of cancer. In order to further explore the mechanism, we used RNA interference to study effects of the inhibition of COX-2 on esophageal squamous cell carcinoma (ESCC) lines. Western blot analysis demonstrated that COX-2 expression was significantly reduced in ESCC cells treated with the COX-2-specific siRNA. Furthermore, the COX-2 siRNA treatment inhibited cell proliferation and induced apoptosis in ESCC cells. In addition, the combination treatment of COX-2 siRNA and acidum acetil salicylicum (aspirin) has a synergistic effect. Therefore, this combination has potential as an anticancer therapy for the treatment of ESCC.
C1 [Li, Zhang] Capital University of Medical Sciences, Beijing Friendship Hospital, Department of Digestive Diseases, 100050 Beijing, China.
[Tu, Jun] University of Texas at San Antonio, Department of Biology, 78249 San Antonio, TX, USA.
[Yu, Zhong-lin] Capital University of Medical Sciences, Beijing Friendship Hospital, Department of Digestive Diseases, 100050 Beijing, China.
[Wu, Yong-dong] Capital University of Medical Sciences, Beijing Friendship Hospital, Department of Digestive Diseases, 100050 Beijing, China.
[Xu, Cai-min] Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, 100005 Beijing, China.
[Zhang, Shu-tian] Capital University of Medical Sciences, Beijing Friendship Hospital, Department of Digestive Diseases, 100050 Beijing, China.
RP Zhang, Sht (reprint author), Capital University of Medical Sciences, Beijing Friendship Hospital, Department of Digestive Diseases, 100050 Beijing, China.
EM niuziyue1@hotmail.com
CR Roth JA, Putnam JB, Rich TA et al, 1997, Cancer of the esophagus. In: Devita VT, Hellman S Jr, Rosenberg SA, eds, Cancer: principles and practice of the oncology. Lippincott-Raven, Philadephia, pp 980–1020
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Li P, Zhang ST, Yu ZL et al, 2009, Effects of cyclooxygenase-2 non-selective and selective inhibitors on proliferation inhibition and apoptosis induction of esophageal squamous carcinoma cells. Dis Esophagus 22:21–31
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 39
EP 45
DI 10.1007/s12253-009-9185-6
PG 7
ER
PT J
AU Zhang, Ch
Tu, Z
Du, Sh
Wang, Y
Wang, Q
AF Zhang, Che
Tu, Ziliang
Du, Shiming
Wang, Yong
Wang, Qibin
TI Expression of Matrix Metalloproteinase 2 and Extracellular Matrix Metalloproteinase Inducer are Unfavorable Postoperative Prognostic Factors in Intrahepatic Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intrahepatic cholangiocarcinoma; MMP-2; EMMPRIN; Clinicopathology; Prognosis
ID Intrahepatic cholangiocarcinoma; MMP-2; EMMPRIN; Clinicopathology; Prognosis
AB Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients’ prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (p=0.03, 0.02), higher TNM stages (p=0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/ EMMPRIN+expression was the lowest (p<0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/EMMPRIN-, MMP-2+/EMMPRIN+, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (p<0.01, p<0.01, p=0.02, p=0.01 and p=0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA.
C1 [Zhang, Che] Yunyang Medical College, Taihe Hospital, 442000 Shiyan, Hubei, China.
[Tu, Ziliang] Yunyang Medical College, Taihe Hospital, 442000 Shiyan, Hubei, China.
[Du, Shiming] Yunyang Medical College, Taihe Hospital, 442000 Shiyan, Hubei, China.
[Wang, Yong] Yunyang Medical College, Taihe Hospital, 442000 Shiyan, Hubei, China.
[Wang, Qibin] Yunyang Medical College, Taihe Hospital, 442000 Shiyan, Hubei, China.
RP Tu, Z (reprint author), Yunyang Medical College, Taihe Hospital, 442000 Shiyan, China.
EM tzl6212@sina.com
CR Itatsu K, Zen Y, Yamaguchi J, 2008, Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts. Hum Pathol 39:710–719
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Davidson B, Givant-Horwitz V, Lazarovici P, Risberg B, Nesland JM, Trope CG, Schaefer E, Reich R, 2003, Matrix metalloproteinases, MMP), EMMPRIN, extracellular matrix metalloproteinase inducer, and mitogen-activated protein kinases, MAPK): co-expression in metastatic serous ovarian carcinoma. Clin Exp Metastas 20:621–631
Sillanpaa S, Anttila M, Suhonen K, Hamalainen K, Turpeenniemi- Hujanen T, Puistola U et al, 2007, Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 2 in epithelial ovarian cancer. Tumour Biol 28:280–289
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 47
EP 53
DI 10.1007/s12253-009-9186-5
PG 7
ER
PT J
AU Guldur, EM
Kibar, Y
Deniz, H
Bakir, K
AF Guldur, Emin Muhammet
Kibar, Yasemin
Deniz, Hale
Bakir, Kemal
TI Comparison of Osteopontin, β-catenin and hnRNP B1 Expression in Lung Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteopontin; Beta-catenin; Heterogeneous nuclear ribonucleoprotein B1; Lung cancer
ID Osteopontin; Beta-catenin; Heterogeneous nuclear ribonucleoprotein B1; Lung cancer
AB This study was performed to compare osteopontin (OPN), β-catenin and heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) immunreactivities in small cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Correlation of these three antibodies with grade and clinicopathologic stage of the tumor in NSCLC was also investigated. Twenty-nine SCLC, 6 large cell carcinoma, 36 adenocarcinoma and 30 squamous cell carcinoma (SCC), totally 101 cases, were included in this study. OPN, β-catenin and hnRNP B1 expressions were immunohistochemically evaluated. OPN positivity was 6.9% in SCLC and 67% in NSCLC. When NSCLC types were individually considered, OPN positivity was 66.7% in large cell carcinoma, 80% in SCC and 55.6% in adenocarcinomas. β-catenin positivity was observed in 48.6% of NSCLC and none of SCLC cases. These results were statistically significant (p<0.05). Neither grade nor stage of NSCLC was correlated with osteopontin, β-catenin or hnRNP B1 immunreactivity. We observed that OPN and β-catenin are useful in differentiating SCLC from NSCLC. This may be helpful in small lung biopsies where morphology is obscured by crush artifacts.
C1 [Guldur, Emin Muhammet] Harran University, Faculty of Medicine, Department of Pathology, 63100 Sanliurfa, Turkey.
[Kibar, Yasemin] Sehitkamil Hospital, Department of PathologyGaziantep, Turkey.
[Deniz, Hale] Gaziantep Children Hospital, Department of Pathology, SehitkamilGaziantep, Turkey.
[Bakir, Kemal] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
RP Deniz, H (reprint author), Gaziantep Children Hospital, Department of Pathology, Gaziantep, Turkey.
EM haleden2000@yahoo.com
CR Coppola D, Szabo M, Boulware D, Muraca P, Alsarraj M, Chambers AF, Yeatman TJ, 2004, Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res 10:184–190
Donati V, Boldrini L, Dell’Omodarme M, Prati MC, Faviana P, Camacci T, Lucchi M, Mussi A, Santoro M, Basolo F, Fontanini G, 2005, Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res 11:6459–6465
Nozawa N, Hashimoto S, Nakashima Y, Matsuo Y, Koga T, Sugio K, Niho Y, Harada M, Sueishi K et al, 2006, Immunohistochemical α and β-catenin and E-cadherin expression and their clinocopathological significance in human lung adenocarcinoma. Pathol Res Pract 202:639–650
Prinen RT, Hirvikoski P, Johansson RT, Hollmen S, Kosma VM, 2001, Reduced expression of α-catenin, β-catenin is associated with high cell proliferative activity and poor differentiation in non-small cell lung cancer. J Clin Pathol 54:391–395
Sueoka E, Sueoka N, Goto Y, Matsuyama S, Nishimura H, Sato M, Fujimura S, Chiba H, Fujiki H, 2001, Heterogeneous nuclear ribonucleoprotein B1 as early cancer biomarker for occult cancer of human lungs and bronchial dysplasia. Cancer Res 61:1896– 1902
Zhou J, Mulshine JL, Unsworth EJ, Scott FM, Avis IM, Vos MD, Treston AM, 1996, Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4. J Biol Chem 271:10760–10766
Zhang J, Takahashi K, Takahashi F, Shimizu K, Ohshita F, Kameda Y, Maeda K, Nishio K, Fukuchi Y, 2001, Differential osteopontin expression in lung cancer. Cancer Lett 171:215–222
Hu Z, Lin D, Yuan J, Xiao T, Zhang H, Sun W, Han N, Ma Y, Di X, Gao M, Ma J, Zhang J, Cheng S, Gao Y, 2005, Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer. Clin Cancer Res 11:4646–4652
Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T, Sugimachi K, 2000, Expression of E-cadherin and β-Catenin in human nonsmall cell lung cancer and the clinical significance. Clin Cancer Res 6:4789–4796
Wu S, Sato M, Endo C, Sakurada A, Dong B, Aikawa H, Chen Y, Okada Y, Matsumura Y, Sueoka E, Kondo T, 2003, HnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung. Lung Cancer 41:179–186
Zech VF, Dlaska M, Tzankov A, Hilbe W, 2006, Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 in non- small cell lung cancer. Cancer Detect Prev 30:395–402
Schneider S, Yochim J, Brabender J, Uchida K, Danenberg KD, Metzger R, Schneider PM, Salonga D, Holscher AH, Danenberg PV, 2004, Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin Cancer Res 10:1588–1596
Choi YS, Shim YM, Kim SH, Son DS, Lee HS, Kim GY, Han J, Kim J, 2003, Prognostic significance of E-cadherin and β-catenin in resected stage 1 non-small cell lung cancer. Eur J Cardiothorac Surg 24:441–449
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 55
EP 59
DI 10.1007/s12253-009-9187-4
PG 5
ER
PT J
AU Ragab, MS
Samaka, MR
Shams, MT
AF Ragab, M Seham
Samaka, M Rehab
Shams, M Tahany
TI HER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Her2/neu; Oncoprotein survival; Wilms tumor; Differentiation
ID Her2/neu; Oncoprotein survival; Wilms tumor; Differentiation
AB Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P>0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank=13.23 and P>0.001), homologous epithelial differentiation (Log-rank=6.01 and P=0.04), as well as HER2/neu positive tumors (Log-rank=6.14 and P=0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank=21.22, P>0.0000) and if HER2/neu positive (Log-rank=8.53, P=0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.
C1 [Ragab, M Seham] Minoufiya University, Pediatric Department, Hematology and Oncology UnitMinoufiya, Egypt.
[Samaka, M Rehab] Minoufiya University, Faculty of Medicine, The Department of PathologyMinoufiya, Egypt.
[Shams, M Tahany] Suez Canal Universities, Faculty of Medicine, The Department of PathologySuez Canal, Egypt.
RP Ragab, MS (reprint author), Minoufiya University, Pediatric Department, Hematology and Oncology Unit, Minoufiya, Egypt.
EM seham172001@yahoo.com
CR Jaffe N, Huff V, 2004, Neoplasms of the kidney. In: Behrman R, Liegman R, Jenson H, eds, Nelson Textbook of Pediactrics. 16th Edition. W.B. Saunder .Ch. 49. p 1711–1714
Lanzkowsky P, 2005, Wilms tumor :manual of pediatric hematology and oncology. 4th ed. Elsevier Academic Press. 19:548–560
Mokhtar N, Gouda I, Adel I, 2007, Cancer Pathology Registry 2003–2004 and Time Trend Analysis. 3:24–39
Ghanem M, Van Der Kwast T, Den Hollander J et al, 2001, Expression and prognostic value of epidermal growth factor receptor, transforming growth factor- alpha, and c-erb-B-2 in nephroblastoma. Cancer 92:3120–3129
Cendron M, Wajsman Z, 2006, http://WWW.e Medicine .com , Inc, Wilms Tumor excerpt. Last Updated: June 29
Egeler R, Wolff J, Anderson R, Coppes M, 1999, Long-term complications and post-treatment follow-up of patients with Wilms’ tumor. Semin Urol Oncol 17(1):55–61
Salem M, Kinoshita Y, Tajiri T et al, 2006, Association between the HER2 expression and histological differentiation in Wilms tumor. Pediatr Surg Int 22:891–896
Potti A, Forseen S, Koka V et al, 2004, Determination of HER-2/ neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors. Cancer Investig 22(4):537–544
Meert A, Martin B, Paesmans M et al, 2003, The role of HER2/ neu expression on the survival of patients with lung cancer: a systemic review of the literature. Br J Cancer 89:959–965
van de Vijver M, 2001, Assessment of the need and appropriate method for testing for the human epidermal growth factor receptor-2(HER2). Eur J Cancer 37:11–17
Perlman E, Grosfeld J, Togashi K, Boccon-Gibod L, 2004, Nephroblastoma. In: Eble N, Sauter G, Epistein J, eds, Pathology and Genetics of tumors of the urinary system and male genital organs, Ch 1. IARC, Lyon, France, pp 48–52
Bozcuk H, Gumus A, Ozbilim G et al, 2005, Cluster analysis of P-Glycoprotein, c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non small cell lung cancer. Med Sci Monit 11(6):11–20
http//www.cancer.gov,2007 Wilms Tumor and Other Childhood Kidney Tumors, PDQ®): Treatment
Fernandes E, Parham D, Ribiro R, Douglas E, 1988, Teratoid Wilms tumor, an important variant of nephroblastoma. J Pediatr Surg 23:1131–1134
Jimenez R, Wallis T, Tabasczka P, Visscher D, 2000, Determination of HER2/neu status in breast carcinoma: comparative analysis of immunohistochemistry and fluorescent in situ hybridization. Mod Path 13:37–45
Dawson B, Trapp R, 2001, Basic and clinical biostatistics :large medical books. Oxford, London. Boston, pp 270–275
Rivera M, Haber D, 2005, Wilms tumor connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer 5:699–713
Matth L, Bianchi F, Prato I et al, 2001, Renal cell cultures for the study of growth factor interactions underlying kidney organogenesis. Invitro Cell Dev Biol Anim 37:251–258
Taub M, Wang Y, Szczesny T, 1990, Epidermal growth factor or transforming growth factor α is required for kidney tubulogenesis in material cultures in serum-free medium. Proc Natl Acad Sci USA 87:4002–4006
Livasy C, Catrina Reading F, Moore D et al, 2006, EGFR expression and HER2/neu overexpression/amplification in endometrial carcinosarcoma. Gynecol Oncol 100:101–106
Nuciforo P, Pellegrini C, Fasani R et al, 2003, Molecular and Immunohistochemical Analysis of HER2/neu Oncogene in Synovial Sarcoma. Human Pathol 34(7):639–645
Green D, Children’s Oncology Group, 2007, Phase III multimodality therapy based on histology, stage, age, and tumor size in children with Wilms’ tumor, clear cell sarcoma of the kidney, or rhabdoid tumors of the kidney, COG-Q9401, Clinical trial, Completed. [PDQ Clinical Trial]
Mitchell C, Jones P, Kelsey A et al, 2000, The treatment of Wilms’ tumour: results of the United Kingdom Children’s cancer study group, UKCCSG, second Wilms’ tumour study. Br J Cancer 83(5):602–608
Ritchey M, Shamberger R, Haase G et al, 2001, Surgical complications after primary nephrectomy for Wilms’ tumor: report from the ntional Wilms’ tumor study group. J Am Coll Surg 192(1):63–68
Yokoi A, McCrudden K, Huang J et al, 2003, Human epidermal growth factor receptor signaling contributes to tumor growth via angiogenesis in her2/neu-expressing experimental Wilms’ tumor. J Peditr Surg 38:1569–1573
Akslen L, Varhaug J, 1995, Oncoprotiens and tumor progression in papillary thyroid. Cancer 76:1643–1654
Sonia L, Ezzat S, Zheng L et al, 1998, Cytoplasmic staining of erbB-2not mRNA levels correlates with differentiation in human thyroid neoplesia. Clinical Endocrinol 49:629–637
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 61
EP 67
DI 10.1007/s12253-009-9188-3
PG 7
ER
PT J
AU Milicevic, MN
Trbojevic-Stankovic, BJ
Drachenberg, BC
Milicevic,
AF Milicevic, M Novica
Trbojevic-Stankovic, B Jasna
Drachenberg, B Cinthia
Milicevic, Zivana
TI Stereologic Analysis of Tissue Compartments of Gunshot-injured and Blunt-injured Spleen
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Blunt-injured spleen; Gunshot-injured spleen; Human; Morphometry; Stereology; Splenic tissue compartments
ID Blunt-injured spleen; Gunshot-injured spleen; Human; Morphometry; Stereology; Splenic tissue compartments
AB The spleen is composed of several tissue compartments and the respective histoquantitative data are essential for complete understanding of immune or pathological processes in this organ. The aim of our study was to determine and compare the stereologic parameters of all tissue compartments of the gunshotinjured and blunt-injured human spleen. The modelbased stereology with point-counting method was utilized to study the volume densities of red pulp, perifollicular zone, marginal zone, white pulp (follicles and periarteriolar lymphoid sheath), and connective tissue. The areal numerical density (the number of follicles per mm2 of tissue section), the numerical density (the number of follicles per mm3 of tissue) of lymphoid follicles and the mean follicle diameter were also determined. Our study provides stereological parameters for all tissue compartments of the human spleen. No morphometric differences were registered between tissue compartments of the blunt-injured and gunshot-injured spleen. As the gunshot-injured spleen was taken as presumably unstimulated in immunological regard, our results suggest that both gunshot-injured and blunt-injured organs may be used as models of the normal human spleen.
C1 [Milicevic, M Novica] Faculty of Medicine, Institute of Histology and Embryology, Visegradska 26, 11000 Belgrade, Serbia.
[Trbojevic-Stankovic, B Jasna] Clinical Centre, Department of HemodialysisBelgrade, Serbia.
[Drachenberg, B Cinthia] University of Maryland, School of Medicine, Department of PathologyBaltimore, MD, USA.
[Milicevic, Zivana] Faculty of Medicine, Institute of Histology and Embryology, Visegradska 26, 11000 Belgrade, Serbia.
RP Milicevic, (reprint author), Faculty of Medicine, Institute of Histology and Embryology, 11000 Belgrade, Serbia.
EM emilicez@sezampro.yu
CR Adkins B, Charyulu V, Sun QL, Lobo D, Lopez DM, 2000, Early block in maturation is associated with thymic involution in mammary tumor-bearing mice. J Immunol 164:5635–5640
Benedict CA, De Trez C, Schneider K, Ha S, Patterson G, Ware CF, 2006, Specific remodeling of splenic architecture by cytomegalovirus. PLoS Pathogy 2:e16., DOI 10.1371/journal. ppat.0020016
Drachenberg CB, Papadimitriou JC, 1996, Splenic pathology in different forms of traumatic injury. Am J Clin Pathol 106:695
Farhi DC, Ashfaq R, 1996, Splenic pathology after traumatic injury. Am J Clin Pathol 105:474–478
Ghosh P, Komschlies KL, Cippitelli M et al, 1995, Gradual loss of T-helper 1 populations in spleen of mice during progressive tumor growth. J Natl Cancer Inst 87:1478–1483
Gunia S, Albrecht K, May M, Stosiek P, 2005, The white pulp in the setting of the septic spleen caused by different bacteria: a comparative morphometric study. APMIS 113:675–682
Hollowood K, Goodlad JR, 1998, Germinal centre cell kinetics. J Pathol 185:229–233
Kappler JW, Hoffmann M, 1973, Regulation of the immune response. III. Kinetic differences between thymus- and bone marrow-derived lymphocytes in the proliferative response to heterologous erythrocytes. J Exp Med 137:1325–1337
Khanna KM, McNamara JT, Lefrancois L, 2007, In situ imaging of the endogenous CD8 T cell response to infection. Science 318:116–120
Leemans R, Manson W, Snijder JA et al, 1999, Immune response capacity after human splenic autotransplantation: restoration of response to individual pneumococcal vaccine subtypes. Ann Surg 229:279–285
Mebius RE, Kraal G, 2005, Structure and function of the spleen. Nat Rev Immunol 5:606–616
Milicevic NM, Cuschieri A, Xuereb A, Milicevic Z, 1996, Stereologic study of splenic tissue compartments from traumatically injured and cancer patients. Gen Diagn Pathol 142:41–44
Milicevic Z, Cuschieri A, Xuereb A, Milicevic NM, 1996, Stereological study of tissue compartments of the human spleen. Histol Histopathol 11:833–836
Robinette CD, Fraumeni JF Jr, 1977, Splenectomy and subsequent mortality in veterans of the 1939–45 war. Lancet 310:127– 129
Segura JA, Barbero LG, Marquez J, 1997, Early tumor effect on splenic Th lymphocytes in mice. FEBS Lett 414:1–6
Stamou KM, Toutouzas KG, Kekis PB et al, 2006, Prospective study of the incidence and risk factors of postsplenectomy thrombosis of the portal, mesenteric, and splenic veins. Arch Surg 141:663–669
Sun QL, Charyulu V, Lobo D, Lopez DM, 2002, Role of thymic stromal cell dysfunction in the thymic involution of mammary tumor-bearing mice. Anticancer Res 22:91–96
Weibel ER, 1979, Practical methods for biological morphometry, vol 1. Academic, New York
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 69
EP 73
DI 10.1007/s12253-009-9189-2
PG 5
ER
PT J
AU Martic, NT
Pecina-Slaus, N
Kusec, V
Kokotovic, T
Musinovic, H
Davor, T
Zeljko, M
AF Martic, Nikuseva Tamara
Pecina-Slaus, Nives
Kusec, Vesna
Kokotovic, Tomislav
Musinovic, Hana
Davor, Tomas
Zeljko, Martina
TI Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Axin; Beta-catenin; Image analysis; Loss of heterozygosity; Neuroepithelial brain tumors; Wnt signaling
ID Axin; Beta-catenin; Image analysis; Loss of heterozygosity; Neuroepithelial brain tumors; Wnt signaling
AB In the present study changes of components of Wnt signaling pathway—axin (AXIN1) and beta-catenin (CTNNB1) in a sample of 72 neuroepithelial brain tumors were investigated. AXIN-1 gene was tested by PCR/loss of heterozygosity (LOH). Immunostaining and image analysis revealed the quantity and localization of relevant proteins. Polymorphic marker for AXIN-1, showed LOH in 11.1% of tumors. LOH was distributed to 6.3% of glioblastomas, one was found in neuroepithelial dysembrioplastic tumor and one in medulloblastoma. Down regulation of axin expression and up regulation of beta-catenin were detected in the analyzed tumors. Axin was observed in the cytoplasm in 68.8% of samples, in 28.1% in both the cytoplasm and nucleus and 3.1% had no expression. Beta-catenin was observed mainly in the nucleus and cytoplasm (59.4%). Expression in 34.4% of samples was in the cytoplasm and 6.3% showed no expression. Comparison of mean values of relative increase of axin and beta-catenin showed that they are significantly reversely proportional (P=0.014). Relative quantity of beta-catenin in patients with gross deletion of AXIN1 was significantly higher in comparison to patients without LOH (P=0.040). Our results demonstrate that changes of key components of the Wnt signaling play a role in neuroepithelial brain tumors.
C1 [Martic, Nikuseva Tamara] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
[Pecina-Slaus, Nives] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
[Kusec, Vesna] Clinical Hospital Centre Zagreb, Clinical Institute of Laboratory Diagnosis, Kispaticeva 12, 10000 Zagreb, Croatia.
[Kokotovic, Tomislav] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
[Musinovic, Hana] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
[Davor, Tomas] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska 29, 10000 Zagreb, Croatia.
[Zeljko, Martina] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
RP Pecina-Slaus, N (reprint author), School of Medicine University of Zagreb, Croatian Institute for Brain Research, Laboratory of Neurooncology, 10000 Zagreb, Croatia.
EM nina@mef.hr
CR Louis DN, Ohgaki H, Wiestler OD et al, 2007, The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Strother DR, Pollack IF, Gisher PG et al, 2002, Tumors of the central nervous system. In: Pizzo PA, Poplack DG, eds, Principles and practice of pediatric oncology. Wiliam, Philadelphia, pp 751–824
Gordon MD, Nusse R, 2006, Wnt signalling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 281:22429–22433
Caricasole A, Bakker A, Copani A et al, 2005, Two sides of the same coin: Wnt signaling in neurodegeneration and neurooncology. Biosci Rep 25:309–327
Luo W, Lin SC, 2004, Axin: a master Scaffold for multiple signaling pathways. Neurosignals 13:99–113
Kikuchi A, 1999, Modulation of Wnt signaling by Axin and Axil. Cytokine Growth Factor Rev 10:255–265
Polakis P, 2007, The many ways of Wnt in cancer. Curr Opin Genet Dev 17:45–51
Patapoutian A, Reichardt LF, 2000, Roles of wnt proteins in neural development maintenance. Curr Opin Neurobiol 10:392–399
Lie DC, Colamarino SA, Song HJ et al, 2005, Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370–1375
Yu X, Malenka RC, 2003, Beta-catenin is critical for dendritic morphogenesis. Nature Neurosci 6:1169–1177
Brakeman JS, Gu SH, Wang XB et al, 1999, Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein. Neuroscience 91:661–672
Pecina-Slaus N, Zigmund M, Kusec Vet al, 2007, E-cadherin and beta-catenin expression patterns in malignant melanoma assessed by image analysis. J Cutan Pathol 34:239–246
Padden M, Leech S, Craig B et al, 2007, Differences in expression of junctional adhesion molecule—a and beta-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junctions pathology. Acta Neuropathol 113:177–186
Cong F, Varmus H, 2004, Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin. Proc Natl Acad Sci USA 101:2882–2887
Anderson CB, Neufeld KL, White RL, 2002, Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. Proc Natl Acad Sci USA 99:8683–8688
Dahmen RP, Koch A, Denkhaus D et al, 2001, Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res 61:7039–7043
Yokota N, Nishizawa S, Ohta S et al, 2002, Role of wnt pathway in medulloblastoma oncogenesis. Int J Cancer 101:198–201
Giangaspero F, Wellek S, Masuoka J et al, 2006, Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol 112:5–12
Ellison DW, Onilude OE, Lindsey JC et al, 2005, United Kingdom children’s cancer study group brain tumour committee. Beta-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom children’s cancer study group brain tumour committee. J Clin Oncol 23:7951–7957
Nikuseva Martic T, Beros V, Pecina-Slaus N et al, 2007, Genetic changes of CDH1, APC and CTNNB1 found in human brain tumors. Pathol Res Pract 203:779–787
Pecina-Slaus N, Nikuseva-Martic T, Beros V et al, 2007, Genetic alterations of E-cadherin and Beta-Catenin in germinoma and teratoma: report of two central nervous system cases. Pathol Oncol Res 13:370–374
Pecina-Slaus N, Nikuseva Martic T, Tomas D et al, 2008, Meningiomas exhibit loss of heterozygosity of the APC gene. J Neurooncol 87:63–70
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 75
EP 79
DI 10.1007/s12253-009-9190-9
PG 5
ER
PT J
AU Huang, LW
Seow, KM
Lee, ChCh
Lin, YH
Pan, HSh
Chen, HJ
AF Huang, Lee-Wen
Seow, Kok-Min
Lee, Chin-Cheng
Lin, Yu-Hung
Pan, Hun-Shan
Chen, Heng-Ju
TI Decreased p21 Expression in HPV-18 Positive Cervical Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus (HPV); p21; p53; p27; Cervical carcinoma
ID Human papillomavirus (HPV); p21; p53; p27; Cervical carcinoma
AB The aim of this study was to investigate the relationship between different human papillomaviruse (HPV) genotypes and the expression of p53, p21 and p27 in cervical carcinomas. A total of 103 cases of cervical carcinomas were assayed for expression of p53, p21 and p27 by immunohistochemistry. HPV typing was carried out by two polymerase chain reaction-based methods. Overall, HPV prevalence was 97.1% among the cervical carcinomas in this study. HPV-16 was detected in 66% of the tumors, HPV-18 in 7.8%, HPV-16/18 in 7.8% and other HPV types in 15.5%. The expression of p53 and p27 was not related to HPV genotype. However, in the HPV-18 positive cervical carcinomas, expression of p21 was significantly decreased or completely absent (P=0.019). Our results indicated that down-regulation of p21 was strongly associated with HPV-18 positive cervical carcinomas. The significantly lower expression of p21 protein in HPV-18 positive samples compared to HPV-18 negative cervical carcinomas supports the hypothesis that inactivation and degradation of p21 proteins by HPV-18 E7 may play an important role in the carcinogenesis of HPV-18 positive cervical neoplasia.
C1 [Huang, Lee-Wen] Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 95 Wen Chang Road, Shih-Lin District, 111 Taipei, Taiwan, Republic of China.
[Seow, Kok-Min] Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 95 Wen Chang Road, Shih-Lin District, 111 Taipei, Taiwan, Republic of China.
[Lee, Chin-Cheng] Taipei Medical University, College of MedicineTaipei, Taiwan, Republic of China.
[Lin, Yu-Hung] Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 95 Wen Chang Road, Shih-Lin District, 111 Taipei, Taiwan, Republic of China.
[Pan, Hun-Shan] Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 95 Wen Chang Road, Shih-Lin District, 111 Taipei, Taiwan, Republic of China.
[Chen, Heng-Ju] Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 95 Wen Chang Road, Shih-Lin District, 111 Taipei, Taiwan, Republic of China.
RP Huang, LW (reprint author), Shin Kong Wu Ho-Su Memorial Hospital, Department of Obstetrics and Gynecology, 111 Taipei, Taiwan, Republic of China.
EM m002057@ms.skh.org.tw
CR Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJF, Peto J, Meijer CJLM, Munoz N, 1999, Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 81
EP 86
DI 10.1007/s12253-009-9191-8
PG 6
ER
PT J
AU Wong, H
Yau, Th
Chan, P
Ng, OLI
Chan, G
Hui, P
Law, LW
Lo, MC
Hedley, JA
Epstein, JR
AF Wong, Hilda
Yau, Thomas
Chan, Pierre
Ng, O L Irene
Chan, Gavin
Hui, Peter
Law, L W
Lo, M C
Hedley, J Antony
Epstein, J Richard
TI PPI-Delayed Diagnosis of Gastrinoma: Oncologic Victim of Pharmacologic Success
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroendocrine carcinoma; Pancreatic tumor; Zollinger–Ellison syndrome; Gastrin; Omeprazole
ID Neuroendocrine carcinoma; Pancreatic tumor; Zollinger–Ellison syndrome; Gastrin; Omeprazole
AB Functional neuroendocrine tumors are often lowgrade malignant neoplasms that can be cured by surgery if detected early, and such detection may in turn be accelerated by the recognition of neuropeptide hypersecretion syndromes. Uniquely, however, relief of peptic symptoms induced by hypergastrinemia is now available from acid-suppressive drugs such as proton-pump inhibitors (PPIs). Here we describe a clinical case in which time to diagnosis from the onset of peptic symptoms was delayed more than 10 years, in part reflecting symptom masking by continuous prescription of the PPI omeprazole.We propose diagnostic criteria for this under-recognized new clinical syndrome, and recommend that physicians routinely measure serum gastrin levels in persistent cases of PPI-dependent dyspepsia unassociated with H. pylori.
C1 [Wong, Hilda] Queen Mary Hospital, Department of Medicine, Division of Hematology/Oncology, Professorial Block, 102 Pokfulam RoadHong Kong, Hong Kong.
[Yau, Thomas] Queen Mary Hospital, Department of Medicine, Division of Hematology/Oncology, Professorial Block, 102 Pokfulam RoadHong Kong, Hong Kong.
[Chan, Pierre] Queen Mary Hospital, Department of Medicine, Division of GastroenterologyHong Kong, Hong Kong.
[Ng, O L Irene] The University of Hong Kong, Queen Mary Hospital, Department of PathologyHong Kong, Hong Kong.
[Chan, Gavin] The University of Hong Kong, Queen Mary Hospital, Department of PathologyHong Kong, Hong Kong.
[Hui, Peter] The University of Hong Kong, Queen Mary Hospital, Department of RadiologyHong Kong, Hong Kong.
[Law, L W] The University of Hong Kong, Queen Mary Hospital, Department of SurgeryHong Kong, Hong Kong.
[Lo, M C] The University of Hong Kong, Queen Mary Hospital, Department of SurgeryHong Kong, Hong Kong.
[Hedley, J Antony] The University of Hong Kong, Department of Community MedicineHong Kong, Hong Kong.
[Epstein, J Richard] Queen Mary Hospital, Department of Medicine, Division of Hematology/Oncology, Professorial Block, 102 Pokfulam RoadHong Kong, Hong Kong.
RP Epstein, JR (reprint author), Queen Mary Hospital, Department of Medicine, Division of Hematology/Oncology, Hong Kong, Hong Kong.
EM repstein@hku.hk;repstein@stvincents.com.au
CR Ellison EC, Sparks J, 2003, Zollinger–Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors? Am J Surg 186:245–8
Corleto VD, Annibale B, Gibril F et al, 2001, Does the widespread use of proton pump inhibitors mask, complicate and/ or delay the diagnosis of Zollinger–Ellison syndrome? Aliment Pharmacol Ther 15:1555–61
Roy PK, Venzon DJ, Shojamanesh H et al, 2000, Zollinger– Ellison syndrome. Clinical presentation in 261 patients. Medicine, Baltimore, 79:379–411
Ellison EH, Wilson SD, 1964, The Zollinger–Ellison syndrome: re-appraisal and evaluation of 260 registered cases. Ann Surg 160:512–30
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Roy PK, Venzon DJ, Feigenbaum KM et al, 2001, Gastric secretion in Zollinger–Ellison syndrome. Correlation with clinical expression, tumor extent and role in diagnosis—-a prospective NIH study of 235 patients and a review of 984 cases in the literature. Medicine, Baltimore, 80:189–222
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Lodish MB, Powell AC, Abu-Asab M et al, 2008, Insulinoma and gastrinoma syndromes from a single intrapancreatic neuroendocrine tumor. J Clin Endocrinol Metab 93:1123–8
Gurevich L, Kazantseva I, Isakov VA et al, 2003, The analysis of immunophenotype of gastrin-producing tumors of the pancreas and gastrointestinal tract. Cancer 98:1967–76
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Ardill JE, Erikkson B, 2003, The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocr Relat Cancer 10:459–62
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van Santen S, van Soest EJ, Busch OR et al, 2007, Awoman with shock as first sign of Zollinger–Ellison syndrome. Ned Tijdschr Geneeskd 151:478–83
Tartaglia A, Vezzadini C, Bianchini S et al, 2005, Gastrinoma of the stomach: a case report. Int J Gastrointest Cancer 35:211–6
Norton JA, Fraker DL, Alexander HR et al, 1999, Surgery to cure the Zollinger–Ellison syndrome. N Engl J Med 341:635–44
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 87
EP 91
DI 10.1007/s12253-009-9192-7
PG 5
ER
PT J
AU Vitanovics, D
Balint, K
Hanzely, Z
Banczerowski, P
Afra, D
AF Vitanovics, Dusan
Balint, Katalin
Hanzely, Zoltan
Banczerowski, Peter
Afra, Denes
TI Ependymoma in Adults: Surgery, Reoperation and Radiotherapy for Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adult ependymoma; Radiotherapy; Reoperation; Surgery
ID Adult ependymoma; Radiotherapy; Reoperation; Surgery
AB Purpose: to retrospectively determine the longterm outcome of adult intracranial ependymoma patients treated with surgery, reoperation, and postoperative radiation therapy. Material and Methods: 61 patients were treated at our institution between 1980 and 2004. Forty patients had World Health Organization (WHO) Grade II ependymoma, and 21 patients had Grade III ependymoma. The median age was 34 years. The majority of patients were female (59%), and 35 had gross total resections (60%). Eighteen patients were reoperated, 15 only once but 2 twice and one six times. Survival times following reoperation was mostly short but some of them reached more than 5 or 10 years. Postoperative radiation therapy was delivered to 31 patients postoperative (55.4%) and to 5 after reoperation, a median total dose of 54 Gy. Results: The median follow-up of surviving patients was 10.6 years. The 5-year and 10-year diseasefree survival rates for all patients were 50% and 32.9% respectively. The 5-year and 10-year overall survival rates for all patients were 57.1% and 39.4%, respectively. A statistically significant effect on prognosis was observed with WHO tumour grade as well as with MIB-1 labelling index. Subtotal resection predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumour location and radiation therapy. Conclusion: In our experience the use of radiotherapy in adult, intracranial WHO Grade II ependymoma patients had no significant effect on prognosis. Radical surgery and eventual reoperation seems to be more favorable.
C1 [Vitanovics, Dusan] National Institute of Neurosurgery, Amerikai ut 57, 1145 Budapest, Hungary.
[Balint, Katalin] National Institute of Neurosurgery, Amerikai ut 57, 1145 Budapest, Hungary.
[Hanzely, Zoltan] National Institute of Neurosurgery, Amerikai ut 57, 1145 Budapest, Hungary.
[Banczerowski, Peter] National Institute of Neurosurgery, Amerikai ut 57, 1145 Budapest, Hungary.
[Afra, Denes] National Institute of Neurosurgery, Amerikai ut 57, 1145 Budapest, Hungary.
RP Afra, D (reprint author), National Institute of Neurosurgery, 1145 Budapest, Hungary.
EM afraden@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 93
EP 99
DI 10.1007/s12253-009-9194-5
PG 7
ER
PT J
AU Hazzaa, MS
Elashry, MO
Afifi, KI
AF Hazzaa, M Sahar
Elashry, M Osama
Afifi, K Ibtesam
TI Clusterin as a Diagnostic and Prognostic Marker for Transitional Cell Carcinoma of the Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Tumor marker; Clusterin; Over-expression; Prognosis
ID Bladder cancer; Tumor marker; Clusterin; Over-expression; Prognosis
AB We investigated the feasibility of profiling and measuring the concentration of clusterin in urine and serum for individuals with transitional cell carcinoma (TCC) of the bladder and comparing it with nontumor controls. In addition, we analyzed the correlation of expression of clusterin in specimens of TCC to various clinicopathologic parameters and prognosis of bladder cancer. Blood and urine samples were used from 68 patients with TCC of the bladder and from 61 patients with benign urological diseases. Enzyme-linked immunosorbent assays (ELISA) were performed for clusterin from serum and urine. Quantitation of clusterin mRNA was carried out in 68 bladder tumor specimens from radical cystectomy or transurethral resection and 26 normal bladder specimens from BPH patients by using RT-PCR method. Correlation for the expression of clusterin mRNA with clinicopathologic parameters was analyzed. Serum and urine clusterin was significantly higher in individuals with bladder cancer than control (p=0.001). Sensitivity and specificity of serum and urine clusterin as a tumor marker for TCC of the bladder was found to be 80%, 91%, 87.1% and 96.7% respectively. Clusterin expression was significantly higher in TCC specimens than normal tissue specimens (P<0.001). Expression of clusterin was significantly higher in patients with invasive TCC of the bladder than that in patients with superficial TCC and control (P<0.001). Overexpression of clusterin mRNA was significantly associated with tumor recurrence and overall survival (p<0.001). The recurrence-free survival time of patients with overexpression of clusterin was significantly shorter than that of patients with weak expression of clusterin (9.8 months vs. 35.2 months). Clusterin may be considered as a potential diagnostic and prognostic biomarker for bladder cancer using urine, serum and/or molecular biology techniques.
C1 [Hazzaa, M Sahar] Tanta University, Faculty of Medicine, Department of PathologyTanta, Egypt.
[Elashry, M Osama] Tanta University, Urology DepartmentTanta, Egypt.
[Afifi, K Ibtesam] Tanta University, Microbiology DepartmentTanta, Egypt.
RP Elashry, MO (reprint author), Tanta University, Urology Department, Tanta, Egypt.
EM oselashry@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 101
EP 109
DI 10.1007/s12253-009-9196-3
PG 9
ER
PT J
AU Zhang, LZ
Mei, J
Qian, ZK
Cai, XS
Jiang, Y
Huang, WD
AF Zhang, Li-Zhi
Mei, Jiong
Qian, Zhi-Kang
Cai, Xuan-Song
Jiang, Yao
Huang, Wei-Da
TI The Role of VE-cadherin in Osteosarcoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VE-cadherin; Osteosarcoma cell; Vasculogenic mimicry; siRNA
ID VE-cadherin; Osteosarcoma cell; Vasculogenic mimicry; siRNA
AB Osteosarcoma cells can generate vasculogeniclike, patterned networks to obtain nutrients and oxygen, which mimic some function of endotheial-like cells and facilitate tumor malignant progress. These cells also express vascular endothelial-cadherin (VE-cadherin), which is generally accepted as a strictly endothelial-specific transmembrane protein. However, its role is still relatively obscure in osteosarcoma cells. So we inhibit the VE-cadherin gene expression with siRNA in osteosarcoma cells (MG63), and culture those cells in three-dimensional medium, containing Type I collagen or Matrigel, to observe the role of VE-cadherin. Western blotting analysis show that sequence-specific siRNA can significantly decrease the expression of VE-cadherin in MG63 cell. After knockdown of VE-cadherin, osteosacoma cells cann’t induced angiogenic sprout and form osteosarcoma-generated, endotheiallike networks. Our data indicate that VE-cadherin may be a positive and specific regulator not only in angiogenesis, but also in vasculogenic mimicry of osteosarcoma cells. And it can be considered as a new prospective option in the combining treatment of aggressive tumor with highly vascularity, including osteosarcoma.
C1 [Zhang, Li-Zhi] Shanghai Jiaotong University, Shanghai Sixth People’s Hospital, Department of Orthopedic Surgery, No. 600 Yishan Road, 200233 Shanghai, China.
[Mei, Jiong] Tongji Hospital Affiliated to Tongji University, Department of Orthopedic Surgery, 200065 Shanghai, China.
[Qian, Zhi-Kang] Fudan University, Department of Biochemistry, 200433 Shanghai, China.
[Cai, Xuan-Song] Tongji Hospital Affiliated to Tongji University, Department of Orthopedic Surgery, 200065 Shanghai, China.
[Jiang, Yao] Shanghai Jiaotong University, Shanghai Sixth People’s Hospital, Department of Orthopedic Surgery, No. 600 Yishan Road, 200233 Shanghai, China.
[Huang, Wei-Da] Fudan University, Department of Biochemistry, 200433 Shanghai, China.
RP Jiang, Y (reprint author), Shanghai Jiaotong University, Shanghai Sixth People’s Hospital, Department of Orthopedic Surgery, 200233 Shanghai, China.
EM jiangyao2005@163.com
CR Maniotis AJ, Folberg R, Hess A et al, 1999, Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752
Lissitzky JC, Parriaux D, Ristorcelli E et al, 2009, Cyclic AMP signaling as a mediator of vasculogenic mimicry in aggressive human melanoma cells in vitro. Cancer Res 69:802– 809
Stevens AP, Spangler B, Wallner S et al, 2009, Direct and tumor microenvironment mediated influences of 5′-deoxy-5′-(methylthio, adenosine on tumor progression of malignant melanoma. J Cell Biochem 106:210–219
Su F, Li B, Wang J, 2009, Molecular regulation of vasculogenic mimicry in human uveal melanoma cells: role of helix-loop-helix Id2, inhibitor of DNA binding 2). Graefes Arch Clin Exp Ophthalmol 247:411–419
Hendrix MJ, Seftor EA, Meltzer PS, 2001, Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc Natl Acad Sci U S A 98:8018–8023
Gavard J, 2009, Breaking the VE-cadherin bonds. FEBS Lett 583:1–6
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Wallez Y, Vilgrain I, Huber P, 2006, Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med 16:55–59
Taddei A, Giampietro C, Conti A et al, 2008, Endothelial adherens junctions control tight junctions by VE-cadherinmediated upregulation of claudin-5. Nat Cell Biol 10:923–934
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Hess AR, Seftor EA, Gruman LM et al, 2006, VE-cadherin regulates EphA2 in aggressive melanoma cells through a novel signaling pathway: implications for vasculogenic mimicry. Cancer Biol Ther 5:228–233
Pezzolo A, Parodi F, Corrias MV et al, 2007, Tumor origin of endothelial cells in human neuroblastoma. J Clin Oncol 25:376–383
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 111
EP 117
DI 10.1007/s12253-009-9198-1
PG 7
ER
PT J
AU Warth, A
Muley, Th
Herpel, E
Pfannschmidt, J
Hoffmann, H
Dienemann, H
Schirmacher, P
Schnabel, AP
AF Warth, Arne
Muley, Thomas
Herpel, Esther
Pfannschmidt, Joachim
Hoffmann, Hans
Dienemann, Hendrik
Schirmacher, Peter
Schnabel, A Philipp
TI A Histochemical Approach to the Diagnosis of Visceral Pleural Infiltration by Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Visceral pleural infiltration (VPI); Staging; Pathology; Elastic layers; Lung cancer; NSCLC; Pleura; Infiltration; Elastic layer; Staining
ID Visceral pleural infiltration (VPI); Staging; Pathology; Elastic layers; Lung cancer; NSCLC; Pleura; Infiltration; Elastic layer; Staining
AB Introduction: Although invasion of the visceral pleura (VPI) by non-small cell lung cancer (NSCLC) is a TNM-relevant diagnostic criterion and is known to affect the patients´ prognoses, until recently there were no standardized or internationally accepted guidelines. This resulted in a diagnostic ambiguity leading to different tumor staging systems and to hardly comparable patient collectives in research studies world wide. The major problem in this issue is to exactly define what constitutes for the diagnosis of VPI with respect to anatomical landmarks. Methods: In order to address this problem we investigated the pleural infiltration depth of 173 NSCLC specimens without lymph node metastases and proven tumor-related death using elastic stains and a scoring system referring to prominent pleural elastic layers, the lamina elastica externa and interna, as anatomical landmarks. Results: Performing comparative Kaplan-Meier survival analyses for each patient collective we could not find any significant difference in the patients´ survival. This indicates that a differential evaluation of the tumor infiltration depth according to the elastic layers is not practicable. Conclusions: Our findings support the consequent application of the recently proposed, pragmatic approach of the international staging committee for lung cancer (IASLC) to define an internationally accepted and standardized staging system for VPI.
C1 [Warth, Arne] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Muley, Thomas] Thoraxklinik Heidelberg, Translational Research UnitHeidelberg, Germany.
[Herpel, Esther] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Pfannschmidt, Joachim] Thoraxklinik Heidelberg, Department of Thoracic SurgeryHeidelberg, Germany.
[Hoffmann, Hans] Thoraxklinik Heidelberg, Department of Thoracic SurgeryHeidelberg, Germany.
[Dienemann, Hendrik] Thoraxklinik Heidelberg, Department of Thoracic SurgeryHeidelberg, Germany.
[Schirmacher, Peter] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
[Schnabel, A Philipp] University of Heidelberg, Department of Pathology, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
RP Warth, A (reprint author), University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
EM arne.warth@med.uni-heidelberg.de
CR World Health Organization classification of tumors, 2004, Pathology and genetics. Tumours of the lung, pleura, thymus and heart. IARC, Lyon
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 119
EP 123
DI 10.1007/s12253-009-9201-x
PG 5
ER
PT J
AU Strenger, V
Urban, Ch
AF Strenger, Volker
Urban, Christian
TI Chromosomal Integration of the HHV-6 Genome as a Possible Cause of Persistent HHV-6 Detection in a Patient with Langerhans Cell Histiocytosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Strenger, Volker] Medical University of Graz, Department of Paediatrics and Adolescent Medicine, Auenbruggerplatz 30, 8036 Graz, Austria.
[Urban, Christian] Medical University of Graz, Department of Paediatrics and Adolescent Medicine, Auenbruggerplatz 30, 8036 Graz, Austria.
RP Strenger, V (reprint author), Medical University of Graz, Department of Paediatrics and Adolescent Medicine, 8036 Graz, Austria.
EM volker.strenger@medunigraz.at
CR Csire M, Mikala G, Jako J et al, 2007, Persistent long-term human herpesvirus 6, HHV-6, infection in a patient with langerhans cell histiocytosis. Pathol Oncol Res 13:157–160
Boutolleau D, Agut H, Gautheret-Dejean A, 2006, Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of active viral infection? J Infect Dis 194:1019–1020 author reply 1021–1013
Caserta MT, Hall CB, Schnabel K, Lofthus G, McDermott MP, 2007, Human herpesvirus, HHV)-6 and HHV-7 infections in pregnant women. J Infect Dis 196:1296–1303
Daibata M, Taguchi T, Nemoto Y, Taguchi H, Miyoshi I, 1999, Inheritance of chromosomally integrated human herpesvirus 6 DNA. Blood 94:1545–1549
Hubacek P, Maalouf J, Zajickova M et al, 2007, Failure of multiple antivirals to affect high HHV-6 DNAaemia resulting from viral chromosomal integration in case of severe aplastic anaemia. Haematologica 92:e98–e100
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Torelli G, Barozzi P, Marasca R et al, 1995, Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo. J Med Virol 46:178– 188
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Hubacek P, Muzikova K, Hrdlickova A et al, 2009, Prevalence of HHV-6 integrated chromosomally among children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic. J Med Virol 81:258–263
Clark DA, Nacheva EP, Leong HN et al, 2006, Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J Infect Dis 193:912– 916
Kamble RT, Clark DA, Leong HN, Heslop HE, Brenner MK, Carrum G, 2007, Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 40:563–566
Clark DA, Tsao EH, Leong HN, Ward KN, Nacheva EP, Griffiths PD, 2006, Reply to Boutolleau et al. and Luppi et al. J Infect Dis 194:1019–1020 author reply 1021–1013
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 125
EP 126
DI 10.1007/s12253-009-9197-2
PG 2
ER
PT J
AU Yu, L
Yang, JSh
AF Yu, Lu
Yang, Jing Shou
TI A Case of Primary Histiocytic Sarcoma Arising from Thyroid Gland
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Histiocytic sarcoma; Thyroid gland; Differential diagnosis; Gene rearrangements; CD163; Immunohistochemistry
ID Histiocytic sarcoma; Thyroid gland; Differential diagnosis; Gene rearrangements; CD163; Immunohistochemistry
AB Histiocytic sarcoma (HS) is an extremely rare true histiocytic malignancy. We report a case of HS arising from thyroid gland in a 69 year-old man. Following subtotal thyroidectomy, a histopathologic, immunohistologic, and genotypic examination revealed HS. This tumor was composed of large spindle or round epithelioid cells with abundant eosinophilic cytoplasm. The neoplastic cells were positive for macrophage-associated antigen CD68, CD163, and lysozymes, as well as CD45, HLA- DR, DP, DQ, and S100, most consistent with a diagnosis of HS. The BIOMED-2 multiplex PCR analysis showed polyclonal Band T-cell populations. To our knowledge, this is the first report of a rare entity HS involving thyroid gland using a comprehensive immunophenotyping panel including CD163 as well as molecular studies to establish the true histiocytic nature of these lesions.
C1 [Yu, Lu] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 17 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
[Yang, Jing Shou] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 17 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
RP Yang, JSh (reprint author), Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
EM yangsj@fmmu.edu.cn
CR Jaffe ES, 2001, Pathology and genetics of tumours of haematopoietic and lymphoid tissues, Vol. 3. IARC Press, Lyon, France
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De Vos FY, Gerding MN, Arends JW, Wegman JJ, 2008, Histiocytic sarcoma localised in the thyroid: a case report. Ann Hematol 87:681–682
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Vos JA, Abbondanzo SL, Barekman CL, Andriko JW, Miettinen M, Aguilera NS, 2005, Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol 18:693–704
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Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan JK, Favera RD, Delsol G, De Wolf-Peeters C, Falini B, Gascoyne RD, Gaulard P, Gatter KC, Isaacson PG, Jaffe ES, Kluin P, Knowles DM, Mason DY, Mori S, Muller-Hermelink HK, Piris MA, Ralfkiaer E, Stein H, Su IJ, Warnke RA, Weiss LM, 2002, Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 41:1– 29
Sun W, Nordberg ML, Fowler MR, 2003, Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol 27:258–265
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Cao M, Eshoa C, Schultz C, Black J, Zu Y, Chang CC, 2007, Primary central nervous system histiocytic sarcoma with relapse to mediastinum: a case report and review of the literature. Arch Pathol Lab Med 131:301–305
Copie-Bergman C, Wotherspoon AC, Norton AJ, Diss TC, Isaacson PG, 1998, True histiocytic lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases. Am J Surg Pathol 22:1386–1392
Kamel OW, Gocke CD, Kell DL, Cleary ML, Warnke RA, 1995, True histiocytic lymphoma: a study of 12 cases based on current definition. Leuk Lymphoma 18:81–86
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Feldman AL, Minniti C, Santi M, Downing JR, Raffeld M, Jaffe ES, 2004, Histiocytic sarcoma after acute lymphoblastic leukaemia: a common clonal origin. Lancet Oncol 5:248–250
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 127
EP 132
DI 10.1007/s12253-009-9193-6
PG 6
ER
PT J
AU Meng, W
Zhou, Y
Zhang, H
Jiang, L
Wang, Z
Li, X
Zhou, H
Chen, Q
Zeng, X
AF Meng, Wenxia
Zhou, Yu
Zhang, Hengyu
Jiang, Lu
Wang, Zhi
Li, Xiaoying
Zhou, Hongmei
Chen, Qianming
Zeng, Xin
TI Nasal-type NK/T-cell Lymphoma with Palatal Ulcer as the Earliest Clinical Manifestation: A Case Report with Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epstein-Barr virus; Granzyme B; Immunohistochemistry; NK/T-cell lymphoma; Ulcer
ID Epstein-Barr virus; Granzyme B; Immunohistochemistry; NK/T-cell lymphoma; Ulcer
AB Extranodal nasal natural killer (NK)/T-cell lymphoma is a very rare kind of lymphoma, Oral cavity involvement of extranodal natural killer/T-cell lymphoma, nasal type is extremely rare, and its clinicopathologic features are also poorly understood. Recently, we experienced an unusual case of Epstein-Barr virus-associated, extranodal NK/T-cell type with a unhealed palatal ulcer as the earliest clinical feature. It is a challenge for oral medicine specialists to make the early diagnosis for this special type of tumor.
C1 [Meng, Wenxia] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Zhou, Yu] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Zhang, Hengyu] Sichuan University, West China Hospital, Department of CardiologySichuan, China.
[Jiang, Lu] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Wang, Zhi] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Li, Xiaoying] Sichuan University, West China College of Stomatology, Department of Oral MedicineSichuan, China.
[Zhou, Hongmei] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Chen, Qianming] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
[Zeng, Xin] Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 14 RenMinNanLu, Section 3, Chengdu, 610041 Sichuan, China.
RP Zeng, X (reprint author), Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, 610041 Sichuan, China.
EM zengxin22@163.com
CR Harris NL, Jaffe ES, Diebold J et al, 1999, World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia November 1997. J Clin Oncol 17:3835–3849
Ng SB, Lai KW, Murugaya S et al, 2004, Nasal-type extranodal natural killer/Tcell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol 17:1097–1107
Jaffe ES, Harris NL, Stein H et al, 2001, WHO classification of tumors: pathology and genetics of tumors of haematopoietic and lymphoid tissues. IARC, Lyon
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Zhang YC, Zhao S, Yu JB, 2008, Gastric involvement of extranodal NK/T-cell lymphoma, nasal type: a report of 3 cases with literature review. Int J Surg Pathol 16:450–4
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Yang C, Ma J, Yang X, 2008, Natural killer/T-cell nasal-type lymphoma: unusual primary spinal tumor. Spine 33:E929–32
Momose A, Mizuno H, Kajihara S, 2006, EBV-associated nasaltype NK/T-cell lymphoma of the nasal cavity/paranasal sinus in a renal allograft recipient. Nephrol Dial Transplant 21:1413–1416
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Went P, Agostinelli C, Gallamini A et al, 2006, Marker expression in peripheral T-cell lymphoma: a proposed clinicalpathologic prognostic score. J Clin Oncol 24:2472–2479
Kim SJ, Kim SJ, Kim BS, Choi CWet al, 2007, Ki-67 expression is predictive of prognosis in patients with stage I/II extranodal NK/T-cell lymphoma, nasal type. Ann Oncol 18:1382–1387
Tao J, Wasik MA, 2001, Epstein-Barr virus associated polymorphic lymphoproliferative disorders occurring in nontransplant settings. Lab Invest 81:429–37
Hoshida Y, Li T, Dong Z et al, 2001, Lymphoproliferative disorders in renal transplant patients in Japan. Int J Cancer 91:869–875
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 133
EP 137
DI 10.1007/s12253-009-9183-8
PG 5
ER
PT J
AU Dundr, P
Pesl, M
Povysil, C
Bauerova, L
Soukup, V
AF Dundr, Pavel
Pesl, Michael
Povysil, Ctibor
Bauerova, Lenka
Soukup, Viktor
TI Primary Large Cell Neuroendocrine Carcinoma of the Kidney
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoma; Kidney; Large cell; Neuroendocrine; Renal tumors
ID Carcinoma; Kidney; Large cell; Neuroendocrine; Renal tumors
AB We report a case of a 56-year-old male with a primary large cell neuroendocrine renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that measured 145×125×100 mm. Histologically, the tumor consisted of large cells with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were irregular, some of them with finely or coarsely granular chromatin, others with vesicular chromatin and prominent nucleoli. The tumor cells showed multiple mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was solid-alveolar, trabecular and cribriform. Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally. Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin CAM5.2, cytokeratin 34βE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin 20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this type have been reported to date.
C1 [Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Pesl, Michael] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Urology, Ke Karlovu 6, 128 00 Prague, Czech Republic.
[Povysil, Ctibor] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Bauerova, Lenka] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Soukup, Viktor] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Urology, Ke Karlovu 6, 128 00 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 128 00 Prague, Czech Republic.
EM pdundr@seznam.cz
CR Lane BR, Chery F, Jour G et al, 2007, Renal neuroendocrine tumours: a clinicopathological study. BJU Int 100:1030–1035
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Ricketts R, Tamboli P, Czerniak B et al, 2008, Tumor-totumor metastasis: report of 2 cases of metastatic carcinoma to angiomyolipoma of the kidney. Arch Pathol Lab Med 132: 1016–1020
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2010
VL 16
IS 1
BP 139
EP 142
DI 10.1007/s12253-009-9180-y
PG 4
ER
PT J
AU Kopper, L
AF Kopper, Laszlo
TI Panitumumab: An Arrow on Target
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Panitumumab; Colorectal cancer; Anti-EGFR therapy
ID Panitumumab; Colorectal cancer; Anti-EGFR therapy
AB Several options are available today in the treatment of advanced colorectal cancer: traditional chemotherapeutic regimens, targeted therapies, and their combinations. Panitumumab is a new, fully human anti-EGFR monoclonal antibody, what is well-tolerated, effective as a single agent in chemotherapy refractory patients and in different combinations. The clinical response is restricted to tumors with wild-type RAS, therefore the RAS status should be checked before treatment.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Foon KA, Yang XD, Weiner LM et al, 2004, Preclinical and clinical evaluation of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 58:984–990
Jakobovits A, Amado RG, Yang X et al, 2007, From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nat Biotechnol 25:1134–1143
Freeman D, McDorman K, Bussh T et al, 2004, Mono and combination-therapeutic activity of panitumumab, ABX-EGF, on human A431 epidermoid and HT-29 colon carcinoma xenografts: correlation with pharmacodynamic parameters. Proc Am Assoc Cancer Res 27–31
Lopez-Albaitero A, Ferris RL, 2007, Immune activation by epidermal growth factor receptor specific monoclonal antibody therapy for head and neck cancer. Arch Otolaryngeal Head Neck Surg 133:1277–1281
Siena S, Sartore-Bianchi A, Di Nicolantonio F et al, 2009, Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308–1324
Barault L, Veyrie N, Jooste V et al, 2008, Mutations in the RASMAPK, PI(3)K, phosphatidylinositol-3-OH kinase, signaling network correlate with poor survival in a population-based series of colonic cancer. Int J Cancer 122:2255–2259
Artale S, Sartore-Bianchi A, Veronese S et al, 2008, Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol 26:4217–4219
Andreyev HJ, Norman AR, Cunningham D et al, 2001, Kirsten ras mutation in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 85:692–696
Van Cutsem E, Peeters M, Siena S et al, 2007, Open-label phase III trial of panitumumab plus best supportive care compared to best supportive care alone in patients with chemotherapy-refractory a metastatic colorectal cancer. J Clin Oncol 25:1658–1664
Amado RG, Wolf M, Peeters M et al, 2008, Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634
Roth A, Tejpar S, Yan P et al, 2009, Correlation of molecular markers in colon cancer with stage-specific prognosis: results of the translational study on the PETACC 3-EORTC 40093-SAKK 60-00 trial. ASCO, Gastrointestinal cancers Symposium, San Francisco, abstract 288
Moroni M, Veronese S, Benvenuti S et al, 2005, Gene copy number for epidermal growth factor receptor, EGFR, and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6:279–286
Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al, 2007, Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to antiepidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648
Lievre A, Bachet JB, Le Corre D et al, 2006, KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995
Monzon FA, Ogino S, Hammond EH et al, 2009, The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch Pathol Lab Med 133:1600–1606
Di Nicolantonio F, Martini M, Molinari F et al, 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705–5712
Sartore-Bianchi A, Martini M, Molinari F et al, 2009, PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851–1857
Prenen H, De Schutter J, Jacobs B et al, 2009, PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 15:3184–3188
Benvenuti S, Frattini M, Arena S et al, 2008, PIK3CAcancer mutations display gender and tissue specificity patterns. Hum Mutat 29:284–288
Van Cutsem E, Kohne CH, Hitre E et al, 2009, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417
Sartore-Bianchi A, Moroni M, Veronese S et al, 2007, Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol 25:3238–3245
Rowinsky EK, Schwartz GH, Gollob JA et al, 2004, Safety, pharmacokinetics, and activity of ABX-EGF, a fully human antiepidermal growth factor receptor monoclonal antibody in patients with metastatic renal cancer. J Clin Oncol 22:3003–3015
Weiner LM, Belldegrun AS, Crawford J et al, 2008, Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res 14:502–508
Lynch TJJ, Kim ES, Eaby B et al, 2007, Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist 12:610–621
Arends R, Yang B, Schwab G et al, 2005, Flexible dosing schedules of panitumumab in cancer patients. J Clin Oncol 23, abstract 3089
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Hecht JR, Patnaik A, Berlin J et al, 2007, Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer 110:980–988
Mitchell EP, Hecht JR, Baranda J et al, 2007, Panitumumab activity in metastatic colorectal cancer, mCRC, petients, pts, with low or negative tumor epidermal growth factor receptor, EGFRr, levels: An updated analysis. J Clin Oncol 25, abstract 4082
Doi T, Ohtsu A, Tahara M et al, 2009, Safety and pharmacokinetics of panitumumab in Japanase ptients with advanced solid tumors. Int J Clin Oncol 14:307–314
Kim R. Cetuximab and panitumumab: are they interchangeable? Lancet Oncol, DOI 10.1016/S1470-2045(09)70312-2
Douillard JS, Cassidy J, Tabermero J et al, 2009, Randomized phase 3 study on panitutumab with FOLFOX4 compared to FOLFOX alone as first-line treatment, tx, for metastatic colorectal cancer, mCRC): the PRIME trial. Eur J Cancer Suppl 7:6
Peeters M, Price T, Hotko Y et al, 2009, Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. Eur J Cancer Suppl 7:2
Hecht JR, Mitchell E, Chidiac T et al, 2009, A randomized phase IIIB trial of chemotherapy, bevacizumab and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27:672–680
Tol J,Koopman M, Cats Aet al, 2009, Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572
Berlin J, Van Cutsem E, Peeters M et al, 2007, Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer, mCRC): a pooled analysis of five clinical trials. J Clin Oncol 25(suppl, abstract 4134
Bencardino K, Ronzoni M, Manzoni M et al, 2008, In vivo biological effects of Panitumumab plus chemotherapy in advanced colorectal cancer patients. J Clin Oncol 26, abstract 14576
Hendlisz A, Marechal R, Durbecq V et al, 2008, Modulation and prognostic value of epidermal growth factor receptor expression in circulating tumor cells during chemotherapy in patients with metastatic colon cancer. J Clin Oncol 26, abstract 15038
Freeman DJ, Juan T, Reiner M et al, 2008, Association of KRAS mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer 7:184–190
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 143
EP 148
DI 10.1007/s12253-010-9257-7
PG 6
ER
PT J
AU Werling, K
Schaff, Zs
Dinya, E
Tulassay, Zs
AF Werling, Klara
Schaff, Zsuzsa
Dinya, Elek
Tulassay, Zsolt
TI Effect of Liver Steatosis on Therapeutic Response in Chronic Hepatitis C Virus Genotype 1 Infected Patients in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatitis C virus; Genotype 1; Steatosis; Therapy
ID Hepatitis C virus; Genotype 1; Steatosis; Therapy
AB Hepatic steatosis seems a frequent histological alteration seen in chronic hepatitis C virus infected patients. There is still a lot to learn about the exact mechanism of effect of liver steatosis and its influence on the progression of liver diseases. Our study involved 96 chronic hepatitis C genotype 1 infected Hungarian patients who received pegylated interferon and ribavirin treatment for the first time. Degree of steatosis, viral and host factors influencing its development and its effect on the efficiency of antiviral treatment were determined. In 61 (64%) of patients the liver tissue showed varying degree of steatosis, which did not show relationship with level of alcohol consumption (p=0.5792), diabetes mellitus (p=0.5925) or body mass index (p=0.9685) in type 1 chronic hepatitis C patients. Degree of steatosis and virus titer showed strong relationship (OR=2.1). Significant relationship was also found between degree of hepatic steatosis and stage (p=0.0119), as well as between therapeutic response to combined pegylated interferon + ribavirin treatment and steatosis (p=0.0012). Our results demonstrated that steatosis has clinical significance in hepatitis C virus genotype 1 infected patients.
C1 [Werling, Klara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Dinya, Elek] EGIS Pharmaceuticals PLC, Medical DepartmentBudapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
RP Werling, K (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM werling@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 149
EP 157
DI 10.1007/s12253-009-9195-4
PG 9
ER
PT J
AU Badid, N
Baba Ahmed, ZF
Merzouk, H
Belbraouet, S
Mokhtari, N
Merzouk, AS
Benhabib, R
Hamzaoui, D
Narce, M
AF Badid, Naima
Baba Ahmed, Zohra Fatima
Merzouk, Hafida
Belbraouet, Slimane
Mokhtari, Nassima
Merzouk, Ahmed Sid
Benhabib, Riad
Hamzaoui, Djalloul
Narce, Michel
TI Oxidant/Antioxidant Status, Lipids and Hormonal Profile in Overweight Women with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Fatty acids; Leptin; Lipids; Lipoproteins; Oxidative stress
ID Breast cancer; Fatty acids; Leptin; Lipids; Lipoproteins; Oxidative stress
AB This study was carried out to determine the relationships between leptin concentrations, lipid alterations, oxidant/ antioxidant status, in vitro LDL oxidizability and LDL-fatty acid composition in overweight breast cancer patients. Glucose, insulin, leptin, lipids, LDL-cholesteryl ester fatty acids, markers of oxidant status (MDA, Hydroperoxides, carbonyl proteins, conjugated dienes) and markers of antioxidant status (vitamins A, C, E, erythrocyte activities of the enzymes superoxide dismutase, SOD, catalase, glutathione peroxidase,GPx, and glutathione reductase, GR and the serum total antioxidant status, ORAC) were investigated in breast cancer patients and in control women. Our findings showed that insulin, leptin, triglyceride, cholesterol and LDL-C concentrations were increased in patients compared to controls. ORAC and vitamin C and E values were lower while plasma hydroperoxide, carbonyl protein and conjugated diene levels, SOD and GPx activities were higher than in controls. Alterations in LDL-fatty acid composition were associated with their enhanced oxidative susceptibility. There were significant positive correlations between leptin concentrations and LDL-C, hydroperoxides, carbonyl proteins, SOD activity, baseline conjugated diene levels and oxidation rate, and significant negative correlations between leptin and ORAC, lag time and LDL-PUFA in patients. In conclusion, breast cancer is associated with lipid alterations and enhanced oxidative stress linked to high leptin levels in overweight.
C1 [Badid, Naima] University of Tlemcen, Faculty of Sciences, Department of Molecular and Cellular BiologyTlemcen, Algeria.
[Baba Ahmed, Zohra Fatima] University of Tlemcen, Faculty of Sciences, Department of Molecular and Cellular BiologyTlemcen, Algeria.
[Merzouk, Hafida] University of Tlemcen, Faculty of Sciences, Department of Molecular and Cellular BiologyTlemcen, Algeria.
[Belbraouet, Slimane] University of Moncton, School of nutritionMoncton, Canada.
[Mokhtari, Nassima] University of Tlemcen, Faculty of Sciences, Department of Molecular and Cellular BiologyTlemcen, Algeria.
[Merzouk, Ahmed Sid] University of Tlemcen, Faculty of EngineeringTlemcen, Algeria.
[Benhabib, Riad] Tlemcen Hospital, Division of Obstetrics and GynecologyTlemcen, Algeria.
[Hamzaoui, Djalloul] Surgery Clinic AVICENEMaghnia, Algeria.
[Narce, Michel] University of Bourgogne, Faculty of Sciences, INSERM UMR 866,Dijon, France.
RP Merzouk, H (reprint author), University of Tlemcen, Faculty of Sciences, Department of Molecular and Cellular Biology, Tlemcen, Algeria.
EM hafidamerzouk_2@hotmail.com
CR World Health Organization, International Agency for Research on Cancer, 2002, IARC handbooks of cancer prevention: breast cancer screening. IRAC, Layon, pp 1–7
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 159
EP 167
DI 10.1007/s12253-009-9199-0
PG 9
ER
PT J
AU Xu, Y
Zhu, M
Zhang, Sh
Liu, H
Li, T
Qin, Ch
AF Xu, Yijun
Zhu, Mingchen
Zhang, Shuhong
Liu, Hui
Li, Tao
Qin, Chengyong
TI Expression and Prognostic Value of PRL-3 in Human Intrahepatic Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intrahepatic cholangiocarcinoma; PRL-3; Lymph node metastasis; Immunochemistry; Prognosis
ID Intrahepatic cholangiocarcinoma; PRL-3; Lymph node metastasis; Immunochemistry; Prognosis
AB Phosphatase of regenerating liver (PRL)-3 is involved in the metastasis of various tumors, but the expression of PRL-3 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. In this study, we assessed the expression levels of PRL-3 by immunohistochemistry in 102 primary ICC samples, 62 matched lymph node metastases (LNM) and 102 adjacent normal liver tissues. Then we investigated the relationship between PRL-3 expression and clinicopathologic factors. Survival analysis was performed to determine the prognostic significance of PRL-3 expression in ICC. Immunochemistry results suggested PRL-3 expression was negative or weak in non-neoplastic intrahepatic bile ducts of adjacent liver tissue. In primary lesion and LNM high PRL-3 expression was frequently detected. Furthermore, the rate of high PRL-3 expression in LNM was higher than that in primary lesion (80.6% vs. 47.1%, P<0.05). High expression of PRL-3 in primary tumors was significantly associated with TNM (P<0.001), T stage (P<0.001), vascular invasion (P=0.002), and LNM (P<0.001). Survival analysis results with Kaplan-Meier method and Cox proportional hazard model indicated high expression of PRL-3 was correlated with decreased overall survival and was an independent prognostic marker of overall survival. Thus, our results suggested high expression of PRL-3 was correlated with progression and metastasis of ICC and indicated negative prognostic impact. PRL-3 might serve as a novel prognostic marker for patients with ICC.
C1 [Xu, Yijun] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Zhu, Mingchen] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, China.
[Zhang, Shuhong] Jinan Central Hospital Affiliated to Shandong University, Department of Gastroenterology, 105 Jiefang Road, 250013 Jinan, China.
[Liu, Hui] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Li, Tao] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Qin, Chengyong] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
RP Qin, Ch (reprint author), Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 250021 Jinan, China.
EM qinchengyong2005@yahoo.cn
CR Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD, 2005, Cholangiocarcinoma. Lancet 366:1303–1314
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 169
EP 175
DI 10.1007/s12253-009-9200-y
PG 7
ER
PT J
AU Raspollini, RM
Stomaci, N
Ringressi, A
Franchi, A
AF Raspollini, Rosaria Maria
Stomaci, Niceta
Ringressi, Andrea
Franchi, Alessandro
TI Primitive Testicular Leiomyosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Testis; Leiomyosarcoma
ID Testis; Leiomyosarcoma
AB Primary testicular leiomyosarcoma is an uncommon tumor with only few cases described in literature. In young people this rare tumor seems to be related to radiotherapy and anabolic steroids abuse. In older people there are apparently no risk factors. We describe one further case in a 77-years old man with full histological and ultrastructural evaluation. A short term follow-up of one year signals no recurrence of the disease.
C1 [Raspollini, Rosaria Maria] AOU Careggi, Department of Human Pathology and Oncology, Viale G.B. Morgagni, 85, 50134 Florence, Italy.
[Stomaci, Niceta] University of Florence, Carreggi Hospital, Urology ClinicFlorence, Italy.
[Ringressi, Andrea] University of Florence, Carreggi Hospital, Urology ClinicFlorence, Italy.
[Franchi, Alessandro] AOU Careggi, Department of Human Pathology and Oncology, Viale G.B. Morgagni, 85, 50134 Florence, Italy.
RP Raspollini, RM (reprint author), AOU Careggi, Department of Human Pathology and Oncology, 50134 Florence, Italy.
EM mariarosaria.raspollini@unifi.it
CR Canales BK, Lukasewycz SJ, Manivel JC, Pryor JL, 2005, Postradiotherapy intratesticular leiomyosarcoma. Urology 66:657. e19–657e.20
Froehner M, Fischer R, Leike S et al, 1999, Intratesticular leiomyosarcoma in a young man after high dose doping with oral-turinabol. Cancer 86:1571–1575
Hachi H, Bougtab A, Amhajji R et al, 2002, A case report of testicular leiomyosarcoma. Med Top Mars 62:531–533
Ali Y, Kehinde EO, Makar R et al, 2002, Leiomyosarcoma complicating chronic inflammation of the testis. Med Principle Pract 11:157–160
Takizawa A, Miura T, Fujinami K et al, 2005, Primary testicular leiomyosarcoma. Int J Urol 12:596–598
Kumar M, Patne SCU, Kumar S, Shukla VK, 2009, Primary highgrade testicular leiomyosarcoma. Indian J Pathol Microbiol 52:91– 93
Eble JN, Sauter G, Epstein JI, Sesterhenn IA, 2004, Tumours of the urinary system and male genital organs. IARC, Lyon
Deveci MS, Deveci G, Onguru O, Kilciler M, Celasum B, 2002, Testicular, gonadal stromal, fibroma: case report and review of the literature. Path International 52:326–330
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 177
EP 179
DI 10.1007/s12253-009-9202-9
PG 3
ER
PT J
AU Mannan, ASRA
Rifaat, AA
Kahvic, M
Kapila, K
Mallik, M
Grover, KV
Bharati, Ch
Perry, A
AF Mannan, Ala Syed Rifat Abul
Rifaat, A Amre
Kahvic, Mirza
Kapila, Kusum
Mallik, Mrinmay
Grover, Kumar Vinod
Bharati, Chandramouli
Perry, Arie
TI Proximal-Type Epithelioid Sarcoma in the Groin Presenting as a Diagnostic Dilemma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Epitheliod sarcoma; FISH; INI1; Immunohistochemistry; Malignant rhabdoid tumor
ID Epitheliod sarcoma; FISH; INI1; Immunohistochemistry; Malignant rhabdoid tumor
AB Epithelioid sarcoma is an uncommon soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Lately, a ‘proximal’ subtype has been described, which occurs in the pelvic and genital areas of somewhat older individuals and tends to behave more aggressively than the conventional subtype. The correct diagnosis of this subtype is essential, since this tumor can be easily mistaken for other malignant tumors that exhibit epithelioid morphology.We report a case of proximal-type epithelioid sarcoma that presented as an inguinal mass in a 47-year-old man. Histologically, the tumor consisted of diffuse sheets of epithelioid cells with scattered rhabdoid morphology. By immunohistochemistry, the neoplastic cells expressed cytokeratin, epithelial membrane antigen, vimentin, CD34, CD99 and showed complete loss of nuclear INI1 protein expression. Fluorescence in situ hybridization was considered borderline for 22q deletion. We present this case to emphasize the importance of diagnosing this uncommon tumor and the role of INI1 immunohistochemistry in establishing the diagnosis.
C1 [Mannan, Ala Syed Rifat Abul] Al Jahra Hospital, Department of Pathology, 02153 Jahra, Kuwait.
[Rifaat, A Amre] Al Jahra Hospital, Department of Pathology, 02153 Jahra, Kuwait.
[Kahvic, Mirza] Al Jahra Hospital, Department of Pathology, 02153 Jahra, Kuwait.
[Kapila, Kusum] Kuwait University, Faculty of Medicine, Department of PathologyKuwait City, Kuwait.
[Mallik, Mrinmay] Mubarak Al Kabir Hospital, Department of CytopathologyJabriya, Kuwait.
[Grover, Kumar Vinod] Al Jahra Hospital, Department of SurgeryJahra, Kuwait.
[Bharati, Chandramouli] Al Jahra Hospital, Department of RadiologyJahra, Kuwait.
[Perry, Arie] Washington University School of Medicine, Department of Pathology and ImmunologySt. Louis, MO, USA.
RP Mannan, ASRA (reprint author), Al Jahra Hospital, Department of Pathology, 02153 Jahra, Kuwait.
EM mannanrifat@rediffmail.com
CR Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD, 1997, “Proximal-type” epithelioid sarcoma: a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol 21:130–146
Roberts CW, Orkin SH, 2004, The SWI/SNF complex-chromatin and cancer. Nat Rev Cancer 4:133–142
Versteege I, Sevenet N, Lange J et al, 1998, Truncating mutation of hSNF5/INI1 in aggressive pediatric cancer. Nature 394:203– 206
Rousseau-Merck MF, Versteege I, Legrand I et al, 1999, hSNF5/ INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors. Cancer Res 59:3152–3156
Biegel JA, Kalpana G, Knudsen ES et al, 2002, The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res 62:323–328
Hoot AC, Russo P, Judkins AR et al, 2004, Immunohistochemical analysis of the hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors. Am J Sug Pathol 28:1485–1491
Sigauke E, Rakheja D, Maddox DL et al, 2006, Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol 19:717–725
Perry A, Fuller CE, Judkins AR, Dehner LP, Biegel JA, 2005, INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas. Mod Pathol 18:951–958
Modena P, Lualdi E, Facchinetti F et al, 2005, SMARCB1/INI1 Tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 65:4012–4019
Hornick JL, Dal Cin P, Fletcher CD, 2009, Loss of INI1 expression is characteristic of both conventional and proximaltype epithelioid sarcoma. Am J Surg Pathol 33:542–550
Chbani L, Guillou L, Terrier P et al, 2009, Epithelioid sarcoma: a clinicopathologic and immunohistochemical study of 106 cases from the French sarcoma group. Am J Clin Pathol 131:22–27
Kohashi K, Izumi T, Oda Y et al, 2009, Infrequent SMARCB1/ INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Hum Pathol 40:349–355
Enzinger FM, 1970, Epithelioid sarcoma: a sarcoma simulating a granuloma or carcinoma. Cancer 26:1029–1041
Hasegawa T, Matsuno Y, Shimoda T, Umeda T, Yokoyama R, Hirohashi S, 2001, Proximal-type epithelioid sarcoma: a clinicopathologic study of 20 cases. Mod Pathol 14:655–663
Daimaru Y, Hashimoto H, Tsuneyoshi M, Enjoji M, 1987, Epithelial profile of epithelioid sarcoma. An immunohistochemical analysis of eight cases. Cancer 59:134–141
Billings SD, Folpe AL, Weiss SW, 2003, Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol 27:48–57
Raoux D, Peoch M, Pedeutour F et al, 2009, Primary epithelioid sarcoma of bone. Report of a unique case, with immunohistochemical and fluorescent in situ hybridization confirmation of INI1 deletion. Am J Surg Pathol 33:954–958
Fanburg-Smith JC, Hengge M, Hengge UR, Smith JS Jr, Miettinen M, 1998, Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and immunohistochemical study of 18 cases. Ann Diagn Pathol 2:351–362
Oda Y, Tsuneyoshi M, 2006, Extrarenal rhabdoid tumors of soft tissue: clinicopathological and molecular genetic review and distinction from other soft-tissue sarcomas with rhabdoid features. Pathol Int 56:287–295
Rekhi B, Gorad BD, Chinoy RF, 2008, Clinicopathological features with outcomes of a series of conventional and proximaltype epithelioid sarcomas, diagnosed over a period of 10 years at a tertiary cancer hospital in India. Virchows Arch 453:141–153
Chase DR, 1997, Do “rhabdoid features” impart a poorer prognosis to proximal-type epithelioid sarcomas? Commentary. Adv Anat Pathol 5:293–295
Livi L, Shah N, Paiar F, Fisher C, Judson I, Moskovic E et al, 2003, Treatment of epithelioid sarcoma at Royal Marsden Hospital. Sarcoma 7:149–152
Suit HD, Russell WO, Martin RG, 1975, Sarcoma of soft tissue: clinical and histopathologic parameters and response to treatment. Cancer 35:1478–1483
Onol FF, Tanidir Y, Kotiloglu E, Bayramicli M, Turhal S, Turkeri LN, 2006, Proximal type epithelioid sarcoma of the scrotum: a source of diagnostic confusion that needs immediate attention. Eur Urol 49:406–407
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 181
EP 188
DI 10.1007/s12253-009-9203-8
PG 8
ER
PT J
AU Guertl, B
Leuschner, I
Guelly, Ch
Ebner, B
Kronberger, C
Hoefler, G
AF Guertl, Barbara
Leuschner, Ivo
Guelly, Christian
Ebner, Birgit
Kronberger, Cornelia
Hoefler, Gerald
TI Is Predisposition for Nephroblastoma Linked to Polymorphisms of the WTX Gene?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE WTX; Nephroblastoma; SNP; HRMA; Polymorphism
ID WTX; Nephroblastoma; SNP; HRMA; Polymorphism
AB Inactivation of Wilms´ tumor X (WTX) gene has been linked to the pathogenesis of a varying percentage of nephroblastomas. In contrast, germline mutations of WTX were identified to cause bone dysplasia, but not to induce the development of nephroblastomas. In our study we investigated whether tumor promotion of nephroblastoma by inactivation of WTX gene is linked to certain single nucleotide polymorphisms (SNPs). Therefore 8 SNPs—distributed over the whole length of the WTX gene—were investigated by high resolution melting curve analysis (HRMA) and sequencing of genomic DNA from nephroblastoma patients (NB) and controls. No difference was detected in the 8 SNPs investigated, which were distributed over the whole length of the gene. Additionally, sequence analysis of the coding part of the WTX gene of the tumor samples revealed no chromosomal aberration. Our study indicates, that inactivation of WTX appears to be a late event in tumorigenesis of nephroblastoma in a subgroup of nephroblastomas.
C1 [Guertl, Barbara] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Leuschner, Ivo] Christian Albrechts University Kiel, Institute of Pathology, Kiel Pediatric Tumor Registry, Michaelisstr. 11, 24105 Kiel, Germany.
[Guelly, Christian] Medical University of Graz, Centre of Medical Research, Stiftingtalstrasse 24, A-8010 Graz, Austria.
[Ebner, Birgit] Medical University of Graz, Centre of Medical Research, Stiftingtalstrasse 24, A-8010 Graz, Austria.
[Kronberger, Cornelia] General Hospital and Paracelsus Medical University Salzburg, Department of Pathology, Muellner Hauptstrasse 48, A-5020 Salzburg, Austria.
[Hoefler, Gerald] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
RP Guertl, B (reprint author), Medical University of Graz, Department of Pathology, A-8036 Graz, Austria.
EM barbara.guertl-lackner@klinikum-graz.at
CR Breslow NE, Olshan A, Beckwith JB et al, 1993, Epidemiology of Wilms tumor. Med Pediatr Oncol 21:178–181
Rivera MN, Kim WJ, Wells J et al, 2007, An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 315:642– 645
Perotti D, Gamba B, Sardella M et al, 2008, Functional inacitvation of the WTX gene is not a frequent event in Wilms´ tumors. Oncogene 27:4625–4632
Lehnerdt GF, Franz P, Winterhoff S et al, 2008, The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx. Laryngoscope 118:2172– 2176
Guertl B, Leuschner I, Harms D, 2006, Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes. Virch Arch 449:171–174
Scott RH, Stiller CA, Walker L et al, 2006,, 2006, Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet 43:705–715
Jenkins ZA, vanKogelenberg M, Morgan T et al, 2009, Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet 41:95–100
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 189
EP 191
DI 10.1007/s12253-009-9205-6
PG 3
ER
PT J
AU Papp, A
Cseke, L
Farkas, R
Pavlovics, G
Horvath, G
Varga, G
Szigeti, A
Bellyei, Sz
Marton, S
Poto, L
Kalmar, K
Vereczkei, A
Pozsgai, E
Horvath, PO
AF Papp, Andras
Cseke, Laszlo
Farkas, Robert
Pavlovics, Gabor
Horvath, Gabor
Varga, Gabor
Szigeti, Andras
Bellyei, Szabolcs
Marton, Sandor
Poto, Laszlo
Kalmar, Katalin
Vereczkei, Andras
Pozsgai, Eva
Horvath, Peter Ors
TI Chemo-radiotherapy in Locally Advanced Squamous Cell Oesophageal Cancer—are Upper Third Tumours more Responsive?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Complete response; Locally advanced tumor; Neoadjuvant therapy; Squamous cell oesophageal cancer
ID Complete response; Locally advanced tumor; Neoadjuvant therapy; Squamous cell oesophageal cancer
AB Before neoadjuvant therapy was widely applied, the prognosis of oesophageal cancer had been considered dependent on the location of the tumor, i.e. upper third cancers had had the worst prognosis. The aim of this retrolective study was to prove the efficiency of the neoadjuvant treatment, and to compare the response of esophageal cancer in different locations. Between January 1998 and September 2005, 102 patients with locally advanced squamous cell oesophageal cancer received preoperative chemo-radiotherapy. In 40 cases the tumor was located in the upper third and in 62 cases in the middle third of the oesophagus. After a four-week-long treatment free period restaging was carried out and patients considered resectable were submitted to surgery. From 40 patients with upper third oesophageal cancer 28 underwent oesophageal resection or pharyngo-laryngectomy. Thiry-five percent a complete histopathological remission was observed. From 62 patients with middle third oesophageal cancer 43 underwent oesophageal resection. Histological examination of the resected specimens documented complete response only in three patients. The median survival and the R0 resection rate were similar in the two groups. Although the resection rate, perioperative morbidity, mortality and the median survival were similar in the two groups, a significantly higher rate of complete response (p<0,05) was observed in patients with upper third oesophageal cancer compared to patients with middle third oesophageal cancer. It seems that upper third oesophageal cancer has superior sensitivity to multimodal treatment therefore our results may support that upper third location is not an unfavorable prognostic factor any more.
C1 [Papp, Andras] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Cseke, Laszlo] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Farkas, Robert] University of Pecs, Department of Oncology, Edesanyak utja 17, H-7624 Pecs, Hungary.
[Pavlovics, Gabor] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Horvath, Gabor] Tawam Medical Center, The Johns Hopkins Medicine International, Department of Radiation Oncology, Al Ain, 1 Tawam Street, 15258 Abu Dhabi, United Arab Emirates.
[Varga, Gabor] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Szigeti, Andras] University of Pecs, Department of Oncology, Edesanyak utja 17, H-7624 Pecs, Hungary.
[Bellyei, Szabolcs] University of Pecs, Department of Oncology, Edesanyak utja 17, H-7624 Pecs, Hungary.
[Marton, Sandor] University of Pecs, Medical Faculty, Department of Anesthesia and Intensive Therapy, Ifjusag u.13, H-7624 Pecs, Hungary.
[Poto, Laszlo] Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, Honved utca 1, H-7624 Pecs, Hungary.
[Kalmar, Katalin] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Vereczkei, Andras] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
[Pozsgai, Eva] University of Pecs, Department of Oncology, Edesanyak utja 17, H-7624 Pecs, Hungary.
[Horvath, Peter Ors] University of Pecs, Department of Surgery, Ifjusag u.13, H-7624 Pecs, Hungary.
RP Papp, A (reprint author), University of Pecs, Department of Surgery, H-7624 Pecs, Hungary.
EM andras.papp@aok.pte.hu
CR Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux Ph, Van Raemdonck D, 2001, Cancer of the esophagus and gastroesophageal junction: potentially curative therapies Surg Oncol 10:113–122
Keighley MRB, 2003, Gastrointestinal cancers in Europe. Aliment Pharmacol Ther 18(Suppl. 3):7–30
Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H, Fink U, 2001, Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg. 234(3):360–367 discussion 368–9
Law S, Kwong DL, Kwok KF, Wong KH, Chu KM, Sham JS, Wong J, 2003, Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy. Ann Surg. 238(3):339– 347 discussion 347–8
P. Sorrentino et al., 1988, Prognostic Significance of Tumor Stage and Lymph Node Involvement in Thoracic Esophageal Cancer. In: J.R. Siewert, A.H.Holscher, ed, Diseases of the esophagus Springer-Verlag Berlin Heidelberg, pp:709–713,
Piessen G, Mariette C, Triboulet JP, 2005, Cervical and upperthird thoracic oesophageal carcinoma: a single pathological entity? Ann Chir. 130(2):86–91
Feinstein AR, 1985, Clinical epidemiology. Saunders, Philadelphia
Horvath OP, Cseke L, Kalmar K, Varga G, Horvath G, 2001, Larynx-preserving pharyngo-esophagectomy after chemoradiation in the treatment of cancer of the pharyngo-esophageal junction. Ann Thorac Surg. 72(6):2146–2147
Pavlovics G, Cseke L, Papp A, Tizedes G, Tabar BA, Horvath PO, 2006, Esophagus reconstruction with free jejunal transfer. Microsurgery 26(1):73–77
Wong R, Malthaner R, 2003, Combined chemotherapy and radiotherapy, without surgery, compared with radiotherapy alone in localised carcinoma of the esophagus, Cochrane Review), in the Cochrane Library, Issue 1. Oxford, Update Softwer
Mariette C, Piessen G, Triboulet JP, 2007, Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 8:545–553
El Nakadi I, Van Laethem JL, Houben JJ, Gay F, Closset J, Van Houtte P, Danhier S, Limbosch JM, Lambilliotte JP, Gelin M, 2002, Squamous cell carcinoma of the esophagus: multi-modal therapy in locally advanced disease. World J Surg 26, 1):72–78
Meneu-Diaz JC, Blazquez LA, Vicente E, Nuno J, Quijano Y, Lopez-Hervas P, Devesa M, Fresneda V, 2000, The role of multimodality therapy for resectable esophageal cancer. Am J Surg 179(6):508–513
Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T, 1997, Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 337(3):161–167
Visser BC, Venook AP, Patti MG, 2003, Adjuvant and neoadjuvant therapy for esophageal cancer: a critical reappraisal. Surg Oncol 12(1):1–7
Urschel JD, Vasan H, 2003, A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 185(6):538–543
Kaklamanos IG, Walker GR, Ferry K, Franceschi D, 2003, Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol 10:754–761
Greer SE, Goodney PP, Sutton JE, Birkmeyer JD, 2005, Neoadjuvant chemoradiotherapy for esophageal carcinoma:a metaanalysis. Surgery 137:172–177
Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J, 2007, Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol 8:226–234
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Berger AC, Farma J, Scott WJ et al., 2005, Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol 23:4330–4337
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Peracchia A, Bonavina L, Botturi M, Pagani M, Via A, Saino G, 2001, Current status of surgery for carcinoma of the hypopharynx and cervical esophagus. Dis Esoph 14:95–97
Liebermann-Meffert DM, Luescher U, Neff U, Ruedi TP, Allgower M, 1987, Esophagectomy without thoracotomy: is there a risk of intramediastinal bleeding? A study on blood supply of the esophagus. Ann Surg 206(2):184–192
Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, Budach W, Teichmann R, Schmitt M, Schmitt G, Franke C, Wilke H, 2005, Chemoradiation with and whitout surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23(10):2310–2317
Bedenne L, Michel P, Bouche O et al., 2002, Randomised phase III trial in locally advanced esophageal cancer: Radiochemotherapy followed by surgery versus radiochemotherapy alone, FFCD 9102). Proc Am Soc Clin Oncol 21:130a abstr 519
Burmeister B, Dickie G, Smithers B, Hodge R, Morton K, 2000, Thirty-four patients with carcinoma of the cervical esophagus treated with chemoradiation therapy. Arch Otolaryngol Head Neck Surg 126:205–208
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 193
EP 200
DI 10.1007/s12253-009-9206-5
PG 8
ER
PT J
AU Szynglarewicz, B
Matkowski, R
Halon, A
Lacko, A
Stepien, M
Forgacz, J
Pudelko, M
Kornafel, J
AF Szynglarewicz, Bartlomiej
Matkowski, Rafal
Halon, Agnieszka
Lacko, Aleksandra
Stepien, Marcin
Forgacz, Jozef
Pudelko, Marek
Kornafel, Jan
TI Association Between Histological Type of Tumour Growth and Patient Survival in T2-T3 Lymph Node-Negative Rectal Cancer Treated with Sphincter-Preserving Total Mesorectal Excision
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anterior resection; Invasive margin character; Lymphocytic infiltration; Rectal cancer; Total mesorectal excision
ID Anterior resection; Invasive margin character; Lymphocytic infiltration; Rectal cancer; Total mesorectal excision
AB For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by logrank test (P<0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P<0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P<0.01). In multivariate analysis these parameters significantly and independently influenced survival (P<0.01 and P<0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.
C1 [Szynglarewicz, Bartlomiej] Wroclaw Medical University, Lower Silesian Oncology Center, 2nd Department of Surgical Oncology, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Matkowski, Rafal] Wroclaw Medical University, Lower Silesian Oncology Center, 2nd Department of Surgical Oncology, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Halon, Agnieszka] Wroclaw Medical University, Department of PathologyWroclaw, Poland.
[Lacko, Aleksandra] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
[Stepien, Marcin] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
[Forgacz, Jozef] Wroclaw Medical University, Lower Silesian Oncology Center, 2nd Department of Surgical Oncology, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Pudelko, Marek] Wroclaw Medical University, Lower Silesian Oncology Center, 2nd Department of Surgical Oncology, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
[Kornafel, Jan] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
RP Matkowski, R (reprint author), Wroclaw Medical University, Lower Silesian Oncology Center, 2nd Department of Surgical Oncology, 53-413 Wroclaw, Poland.
EM matkowski.r@dco.com.pl
CR Heald RJ, Husband EM, Ryall RDH, 1982, The mesorectum in rectal cancer surgery- the clue to pelvic recurrence? Br J Surg 69:613–616
Dorudi S, Steele RJ, McArdle CS, 2002, Surgery for colorectal cancer. Br Med Bull 64:101–118
Cecil TD, Sexton R, Moran BJ, Heald RJ, 2004, Total mesorectal excision results in low local recurrence rates in lymph nodepositive rectal cancer. Dis Colon Rectum 47:1145–1149
Colquhoun P, Wexner SD, Cohen A, 2003, Adjuvant therapy is valuable in the treatment of rectal cancer despite total mesorectal excision. J Surg Oncol 83:133–139
Merchant NB, Guillem JG, Paty PB et al, 1999, T3N0 rectal cancer: results following sharp mesorectal excision and no adjuvant therapy. J Gastrointest Surg 3:642–647
Price T, Pittman K, Patterson W et al, 2008, Management and survival trends in colorectal cancer. Clin Oncol 20:626–630
Jass JR, Love S, Northover JM, 1987, A new prognostic classification for rectal cancer. Lancet 1:1303–1306
Jass JR, O’Brien MJ, Riddel HR et al, 2007, Recommendations for the reporting of surgically resected specimens of colorectal carcinoma. Virchows Arch 450:1–13
Szynglarewicz B, Matkowski R, Forgacz J et al, 2007, Clinical factors in prediction of prognosis after anterior resection with total mesorectal excision for carcinoma of the rectum. Oncol Rep 17:471–476
Katsumata D, Fukui H, Ono Y et al, 2008, Depth of tumor invasion in locally advanced rectal cancer correlates with patient’s prognosis: the usefulness of elastic stain for its measurement. Surg Today 38:115–122
Bori R, Sejben I, Svebis M et al, 2009, Heterogeneity of pT3 colorectal carcinomas according to the depth of invasion. Pathol Oncol Res, in press). doi 10.1007/s12253-009-9149-x
Miyoshi M, Ueno H, Hashiguchi Y et al, 2006, Extent of mesorectal tumor invasion as a prognostic factor after curative surgery for T3 rectal cancer patients. Ann Surg 243:492–498
Yoshida K, Yoshimatsu K, Otani T et al, 2008, The depth of tumor invasion beyond the outer border of the muscularis propria as a prognostic factor for T3 rectal/rectosigmoid cancer. Anticancer Res 28:1773–1778
Szynglarewicz B, Matkowski R, Maciejczyk A et al, 2008, Combined-modality therapy with sphincter-preserving total mesorectal excision for locally advanced rectal cancer: patient’s age and long-term outcome. J Gastrointestin Liver Dis 17:49–52
Compton CC, 2003, Colorectal carcinoma: Diagnostic, Prognostic, and Molecular Features. Mod Pathol 16:376–388
Nagtegaal I, Gaspar C, Marijnen C et al, 2004, Morphological changes in tumour type after radiotherapy are accompanied by changes in gene expression profile but not in clinical behaviour. J Pathol 204:183–292
Sternberg A, Mizrahi A, Amar M, Groisman G, 2006, Detection of venous invasion in surgical specimens of colorectal carcinoma: the efficacy of various types of tissue blocks. J Clin Pathol 59:207–210
Harrison JC, Dean PJ, el-Zeky F et al, 1994, From Dukes to Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 25:498–505
Quirke P, Dixon MF, Clayden AD et al, 1987, Prognostic significance of DNA aneuploidy and cell proliferation in rectal adenocarcinomas. J Pathol 151:285–291
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 201
EP 206
DI 10.1007/s12253-009-9207-4
PG 6
ER
PT J
AU Olasz, L
Szalma, J
Orsi, E
Tornoczky, T
Marko, T
Nyarady, Z
AF Olasz, Lajos
Szalma, Jozsef
Orsi, Eniko
Tornoczky, Tamas
Marko, Tamas
Nyarady, Zoltan
TI Neoadjuvant Chemotherapy: Does It Have Benefits for the Surgeon in the Treatment of Advanced Squamous Cell Cancer of the Oral Cavity?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OSCC; Neoadjuvant chemotherapy; Surgical margin; Primary tumor regression; Oral cancer
ID OSCC; Neoadjuvant chemotherapy; Surgical margin; Primary tumor regression; Oral cancer
AB The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin—Vincristin—Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2–4 cm 28%; 4–6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III–IV) were not observed. There was a significant decrease in size (P<0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don’t suggest surgery in T4A.
C1 [Olasz, Lajos] University of Pecs, Department of Oral and Maxillofacial Surgery, Dischka Gy. u.5., 7621 Pecs, Hungary.
[Szalma, Jozsef] University of Pecs, Department of Oral and Maxillofacial Surgery, Dischka Gy. u.5., 7621 Pecs, Hungary.
[Orsi, Eniko] University of Pecs, Department of Oral and Maxillofacial Surgery, Dischka Gy. u.5., 7621 Pecs, Hungary.
[Tornoczky, Tamas] University of Pecs, Department of Pathology, Szigeti Str. 12, 7624 Pecs, Hungary.
[Marko, Tamas] University of Pecs, Department of Informatics, Szigeti Str. 12, 7624 Pecs, Hungary.
[Nyarady, Zoltan] University of Pecs, Department of Oral and Maxillofacial Surgery, Dischka Gy. u.5., 7621 Pecs, Hungary.
RP Olasz, L (reprint author), University of Pecs, Department of Oral and Maxillofacial Surgery, 7621 Pecs, Hungary.
EM lajos.olasz@aok.pte.hu
CR Gaudi I, Kasler M, 2002, The course of cancer mortality in Hungary between 1975–2001, English abstract). Magy Onkol 46:291–295
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Woolgar JA, Rogers SN, Lowe D et al, 2003, Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread. Oral Oncol 39:130–137
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 207
EP 212
DI 10.1007/s12253-009-9208-3
PG 6
ER
PT J
AU Urbanowicz, I
Mazur, G
Stacherzak-Pawlik, J
Bogunia-Kubik, K
Wrobel, T
Wozniak, M
Kuliczkowski, K
AF Urbanowicz, Iwona
Mazur, Grzegorz
Stacherzak-Pawlik, Jolanta
Bogunia-Kubik, Katarzyna
Wrobel, Tomasz
Wozniak, Mieczyslaw
Kuliczkowski, Kazimierz
TI IFN Gamma Gene Polymorphism May Contribute to the Susceptibility to CLL
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chronic lymphocytic leukemia; Gene polymorphism; INF gamma
ID Chronic lymphocytic leukemia; Gene polymorphism; INF gamma
AB The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked with the production and activity of certain growth factors. However a significant proportion of CLL patients display immune abnormalities suggestive of aberrant cytokine secretion and/or response. In contrast to B lymphocytes, T cells of B-CLL patients characterise with the increased production of interferongamma (IFN-γ) and this cytokine has been indicated to prevent malignant cells from entering apoptosis including the slowly expanding population of CD5+ B cells that characterizes chronic lymphocytic leukemia. The aim of the present study was to assess whether functionally relevant interferon-gamma gene (IFNG) polymorphism (+847 A/T) contributes to the pathogenesis of B-CLL. In total 110 individuals was investigates, including 61 CLL patients and 50 healthy individuals. The presence of the IFNG AA genotype was found to be associated with susceptibility to CLL (23/61 vs. 7/50, p<0.005, for patients and controls, respectively). This results suggest that individuals rather prone to the lower level of IFN-γ production (associated with the presence of the A allele) appear to be more susceptible to this malignant disease.
C1 [Urbanowicz, Iwona] Wroclaw Medical University, Department of Clinical Chemistry, Pasteur 2 Str, 50-367 Wroclaw, Poland.
[Mazur, Grzegorz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Stacherzak-Pawlik, Jolanta] Wroclaw Medical University, Department of Clinical Chemistry, Pasteur 2 Str, 50-367 Wroclaw, Poland.
[Bogunia-Kubik, Katarzyna] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental TherapyWroclaw, Poland.
[Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Wozniak, Mieczyslaw] Wroclaw Medical University, Department of Clinical Chemistry, Pasteur 2 Str, 50-367 Wroclaw, Poland.
[Kuliczkowski, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
RP Urbanowicz, I (reprint author), Wroclaw Medical University, Department of Clinical Chemistry, 50-367 Wroclaw, Poland.
EM IwonaUrb@yahoo.com
CR Abbott BL, 2004, Advances in the diagnosis and treatment of chronic lymphocytic leukemia. Clin Adv Hematol Oncol 2:448–454
Zenz T, Mertens D, Dohner H, Stilgenbauer S, 2008, Molecular diagnostics in chronic lymphocytic leukemia—Pathogenetic and clinical implications. Leuk Lymphoma 15:1–10
Mainou-Fowler T, Prentice AG, 1996, Modulation of apoptosis with cytokines in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 21:369–377
Pravica V, Perrey C, Stevens A et al, 2000, A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61:863–866
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Perrey C, Pravica V, Sinnott PJ, Hutchinson IV, 1998, Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factoralpha genes: a technical report. Transpl Immunol 6:193–197
Bogunia-Kubik K,Mazur G, Urbanowicz I,Wrobel T, Kuliczkowski K, Wozniak M, Lange A, 2006, Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukemia. Int J Immunogenet 33:21–24
Kiaii S, Choudhury A, Mozaffari F, Rezvany R, Lundin J, Mellstedt H, Osterborg A, 2006, Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia: long-term effects of fludarabine and alemtuzumab treatment. Leuk Lymphoma 47:1229–1238
Kiaii S, Choudhury A, Mozaffari F, Kimby E, Osterborg A, Mellstedt H, 2005, Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia, B-CLL): comparison of indolent and progressive disease. Med Oncol 22:291–302
Rossmann ED, Lewin N, Jeddi-Tehrani M, Osterborg A, Mellstedt H, 2002, Intracellular T cell cytokines in patients with B cell chronic lymphocytic leukaemia, B-CLL). Eur J Haematol 68:299– 306
Podhorecka M, Dmoszynska A, Rolinski J, 2004, Intracellular IFN-gamma expression by CD3+/CD8+ cell subset in B-CLL patients correlates with stage of the disease. Eur J Haematol 73:29–35
Totero D, Tazzari PL, Capaia M, Montera MP, Clavio M, Balleari E, Foa R, Gobbi M, 2003, CD40 triggering enhances fludarabineinduced apoptosis of chronic lymphocytic leukemia B-cells through autocrine release of tumor necrosis factor-alpha and interferon-gama and tumor necrosis factor receptor-I-II upregulation. Haematologica 88:148–158
Gallego A, Vargas JA, Castejon R, Citores MJ, Romero Y, Millan I, Durantez A, 2003, Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL. Cytometry B Clin Cytom 56:23–29
Warle MC, Farhan A, Metselaar HJ et al, 2003, Are cytokine gene polymorphisms related to in vitro cytokine production profiles? Liver Transpl 9:170–181
Vandenbroeck K, Goris A, 2003, Cytokine gene polymorphisms in multifactorial diseases: gateways to novel targets for immunotherapy? Trends Pharmacol Sci 24:284–289
Zaki M, Douglas R, Patten N, Bachinsky M, Lamb R, Nowell P, Moore J, 2000, Disruption of the IFN-gamma cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis. Leuk Res 24:611–621
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 213
EP 216
DI 10.1007/s12253-009-9209-2
PG 4
ER
PT J
AU Chua, CT
Yao, P
Akther, J
Morris, LD
AF Chua, C Terence
Yao, Peng
Akther, Javed
Morris, L David
TI Impact of Tumor Angiogenesis in Peritoneal Mesothelioma After Radical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mesothelioma; Vascular Endothelial Growth Factor; CD 31 Antigen; Angiogenesis; Cytoreductive surgery
ID Mesothelioma; Vascular Endothelial Growth Factor; CD 31 Antigen; Angiogenesis; Cytoreductive surgery
AB Peritoneal mesothelioma is one of the peritoneal surface malignancies where long-term survival is a reality after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Tumor angiogenesis has been shown to be of prognostic significance on survival in mesothelioma. We investigated the impact of survival of patients with peritoneal mesothelioma following CRS and HIPEC to determine the impact of tumor angiogenesis on survival after this radical surgical treatment. Paraffin sections of 23 patients who were treated with CRS and HIPEC were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies (VEGF-C and CD31) on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). VEGF expression and microvessel density (MVD) using CD31 staining were studied. The median survival was 94 months with a 3-year survival rate of 51%. There was no impact on patient’s age, sex, peritoneal cancer index, tumor histopathology and survival outcomes between patients with low or high MVD and VEGF expression. After CRS and HIPEC, our results demonstrate that the prognostic significance of tumor angiogenesis is negated, highlighting the potential importance of other co-contributory mechanisms in mesotheliomagenesis and undergoing radial treatment.
C1 [Chua, C Terence] St George Hospital, University of New South Wales, Department of Surgery, Kogarah, NSW 2217 Sydney, Australia.
[Yao, Peng] St George Hospital, University of New South Wales, Department of Surgery, Kogarah, NSW 2217 Sydney, Australia.
[Akther, Javed] St George Hospital, University of New South Wales, Department of Surgery, Kogarah, NSW 2217 Sydney, Australia.
[Morris, L David] St George Hospital, University of New South Wales, Department of Surgery, Kogarah, NSW 2217 Sydney, Australia.
RP Morris, LD (reprint author), St George Hospital, University of New South Wales, Department of Surgery, NSW 2217 Sydney, Australia.
EM david.morris@unsw.edu.au
CR Chua TC, Yan TD, Morris DL, 2009, Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management. Can J Surg 52(1):59–64
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Masood R, Kundra A, Zhu S, Xia G, Scalia P, Smith DL et al, 2003, Malignant mesothelioma growth inhibition by agents that target the VEGF and VEGF-C autocrine loops. Int J Cancer 104, 5):603–610
Edwards JG, Cox G, Andi A, Jones JL, Walker RA, Walker DA et al, 2001, Angiogenesis is an independent prognostic factor in malignant mesothelioma. Br J Cancer 85(6):863–868
Demirag F, Unsal E, Yilmaz A, Caglar A, 2005, Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma. Chest 128(5):3382–3387
Kothmaier H, Quehenberger F, Halbwedl I, Morbini P, Demirag F, Zeren H et al, 2008, EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors. Thorax 63(4):345–351
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Konig JE, Tolnay E, Wiethege T, Muller KM, 1999, Expression of vascular endothelial growth factor in diffuse malignant pleural mesothelioma. Virchows Arch 435(1):8–12
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Zanella CL, Posada J, Tritton TR, Mossman BT, 1996, Asbestos causes stimulation of the extracellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res 56(23):5334– 5338
Gazdar AF, Carbone M, 2003, Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40. Clin Lung Cancer 5(3):177–181
Aoe K, Hiraki A, Tanaka T, Gemba K-I, Taguchi K, Murakami T et al, 2006, Expression of vascular endothelial growth factor in malignant mesothelioma. Anticancer Res 26(6C):4833–4836
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 217
EP 222
DI 10.1007/s12253-009-9210-9
PG 6
ER
PT J
AU Kruszyna,
Lianeri, M
Rydzanicz, M
Szyfter, K
Jagodzinski, PP
AF Kruszyna, Lukasz
Lianeri, Margarita
Rydzanicz, Malgorzata
Szyfter, Krzysztof
Jagodzinski, P Pawel
TI SDF1-3'A Gene Polymorphism is Associated with Laryngeal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SDF1-3’ G801A; Polymorphism; Laryngeal cancer; CXCR4; PCR-RFLP
ID SDF1-3’ G801A; Polymorphism; Laryngeal cancer; CXCR4; PCR-RFLP
AB The SDF1-3’ G801A (rs 1801157) polymorphism is associated with increased risk of various types of cancers, including those of the neck and head. Using PCR-RFLPs, we investigated the distribution of SDF1-3′ G801A genotypes in patients with laryngeal cancer (n=118) and controls (n=250) in Poland. We found that patients with SDF1-3’ A/A and G/A genotypes exhibit a 1.863-fold increased risk of laryngeal cancer (95% CI=1.177–2.949, p=0.0086). However, there was no significant increase in risk for the homozygous SDF1-3’ A/A genotype OR=3.235 (95% CI=0.5330−19.633, p=0.3329). We also did not observe a significant association between tumor characteristics and prevalence of alleles or genotypes for the SDF1-3′ G801A polymorphism. Our findings suggest that the SDF1-3'A variant may be associated with an increased risk of laryngeal cancer.
C1 [Kruszyna, Lukasz] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Lianeri, Margarita] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Rydzanicz, Malgorzata] Polish Academy of Sciences, Institute of Human Genetics, Department of Environmental MutagenesisPoznan, Poland.
[Szyfter, Krzysztof] Polish Academy of Sciences, Institute of Human Genetics, Department of Environmental MutagenesisPoznan, Poland.
[Jagodzinski, P Pawel] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
RP Jagodzinski, PP (reprint author), Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznan, Poland.
EM pjagodzi@am.poznan.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 223
EP 227
DI 10.1007/s12253-009-9214-5
PG 5
ER
PT J
AU Ren, K
Zhang, W
Shi, Y
Gong, J
AF Ren, Ke
Zhang, Wei
Shi, Yujun
Gong, Jianping
TI Pim-2 Activates API-5 to Inhibit the Apoptosis of Hepatocellular Carcinoma Cells Through NF-κB Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pim-2; NF-κB; API-5; Hepatocellular carcinoma cells; Apoptosis
ID Pim-2; NF-κB; API-5; Hepatocellular carcinoma cells; Apoptosis
AB Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear.We studied the relationship among Pim-2,NF-κBand API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, aswell as NF-κB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-κB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-κB and API-5, as well as NF-κB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-κB and API-5, as well as NF-κB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-κB is the key regulator.
C1 [Ren, Ke] The Second Affiliated Hospital of Chongqing Medical University, Department of Hepatobiliary SurgeryChongqing, China.
[Zhang, Wei] The Second Affiliated Hospital of Chongqing Medical University, Department of Hepatobiliary SurgeryChongqing, China.
[Shi, Yujun] Sichuan University, West China HospitalChengdu, China.
[Gong, Jianping] The Second Affiliated Hospital of Chongqing Medical University, Department of Hepatobiliary SurgeryChongqing, China.
RP Gong, J (reprint author), The Second Affiliated Hospital of Chongqing Medical University, Department of Hepatobiliary Surgery, Chongqing, China.
EM gongjianping11@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 229
EP 237
DI 10.1007/s12253-009-9215-4
PG 9
ER
PT J
AU Seow, FH
Yip, KW
Loh, WH
Ithnin, H
Por, P
Rohaizak, M
AF Seow, Fong Heng
Yip, Kien Wai
Loh, Woon Hui
Ithnin, Hairuszah
Por, Patricia
Rohaizak, Mohammad
TI Immunohistochemical Detection of Phospho-Akt, Phospho-BAD, HER2 and Oestrogen Receptors α and β in Malaysian Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Akt; Oestrogen receptor; HER2
ID Breast cancer; Akt; Oestrogen receptor; HER2
AB Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-α, ER-β, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-α, nuclear ER-β, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-α expression was inversely correlated with HER2 and Ki-67 (P=0.041 and P=0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P=0.012). No relationship of Akt phosphorylation with HER2, ER-α or ER-β was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P=0.036 or P=0.009). The higher Ki-67 and lower ER-α expression showed an association with patient age of <50 years (P=0.004) and with positive nodal status (P=0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.
C1 [Seow, Fong Heng] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Selangor, Malaysia.
[Yip, Kien Wai] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Selangor, Malaysia.
[Loh, Woon Hui] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Selangor, Malaysia.
[Ithnin, Hairuszah] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Selangor, Malaysia.
[Por, Patricia] Assunta Hospital, Jalan Templer, 46990 Petaling Jaya, Selangor, Malaysia.
[Rohaizak, Mohammad] Hospital Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Surgery, 56000 Cheras, Malaysia.
RP Seow, FH (reprint author), Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Malaysia.
EM shf@medic.upm.edu.my
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Stal O, Perez-Tenorio G, Akerberg L et al, 2003, Akt kinases in breast cancer and the results of adjuvant therapy. Breast Cancer Res 5:R37–R44
Zhou X, Tan M, Stone Hawthorne Vet al, 2004, Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res 10:6779–6788
Hill MM, Hemmings BA, 2002, Inhibition of protein kinase B/ Akt. implications for cancer therapy. Pharmacol Ther 93:243–251
Zha J, Harada H, Yang E et al, 1996, Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87:619–628
Fernando RI, Wimalasena J, 2004, Estradiol abrogates apoptosis in breast cancer cells through inactivation of BAD: Ras-dependent nongenomic pathways requiring signaling through ERK and Akt. Mol Biol Cell 15:3266–3284
Krasilnikov MA, 2000, Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry, Mosc, 65:59–67
Liao Y, Hung MC, 2003, Regulation of the activity of p38 mitogen-activated protein kinase by Akt in cancer and adenoviral protein E1A-mediated sensitization to apoptosis. Mol Cell Biol 23:6836–6848
Yonemori K, Tsuta K, Shimizu C, et al, 2009, Immunohistochemical expression of PTEN and phosphorylated Akt are not correlated with clinical outcome in breast cancer patients treated with trastuzumab-containing neo-adjuvant chemotherapy. Med Oncol 26:344-349
Klauber-DeMore N, 2005, Tumor biology of breast cancer in young women. Breast Dis 23:9–15
Hartley MC, McKinley BP, Rogers EA et al, 2006, Differential expression of prognostic factors and effect on survival in young, < or =40, breast cancer patients: a case-control study. Am Surg 72:1189–1194 discussion 1194-5
HusseinMR, Abd-Elwahed SR, Abdulwahed AR, 2008, Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast. Cell Biol Int 32:698–707
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 239
EP 248
DI 10.1007/s12253-009-9216-3
PG 10
ER
PT J
AU Zidar, N
Zver, S
Jurcic, V
AF Zidar, Nina
Zver, Samo
Jurcic, Vesna
TI Extraosseus Plasmacytoma of the Pharynx with Localized Light Chain Deposition. Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Light chain deposition disease; Isolated; Pharynx; Extraosseus plasmacytoma
ID Light chain deposition disease; Isolated; Pharynx; Extraosseus plasmacytoma
AB Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. It is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD, i.e. in the brain, lungs and cervical lymph nodes. We here report on another patient with an isolated form of LCDD, which was limited to the pharyngeal mucosa and was associated with an extraosseus plasmacytoma of the pharynx, expanding the spectrum that has been recognized for LCDD. The patient was treated by local radiotherapy, with an excellent response. A less aggressive clinical course can probably be expected than in the usual form of LCDD, but a longterm follow-up is necessary to establish the clinical significance of this variant of LCDD.
C1 [Zidar, Nina] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia.
[Zver, Samo] University Medical Centre Ljubljana, Department of Haematology, Zaloska 7, 1525 Ljubljana, Slovenia.
[Jurcic, Vesna] University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, 1000 Ljubljana, Slovenia.
RP Zidar, N (reprint author), University of Ljubljana, Faculty of Medicine, Institute of Pathology, 1000 Ljubljana, Slovenia.
EM nina.zidar@mf.uni-lj.si
CR Lin J, Markowitz GS, Valeri AM, Kambham N, Sherman WH, Appel GB et al, 2001, Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol 12:1482–1492
Pozzi C, Locatelli F, 2002, Kidney and liver involvement in monoclonal light chain disorders. Semin Nephrol 22:319–330
Pozzi C, D’Amico M, Fogazzi GB, Curioni S, Ferrario F, Pasquali S et al, 2003, Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis 42:1154–1163
McKenna RW, Kyle RA, Kuehl WM, Grogan TM, Harris NL, Coupland RW, 2008, Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds, WHO classification of tumours of haemopoietic and lymphoid tissues, 2nd edn. IARC, Lyon, pp 200–213
Popovic M, Tavcar R, Glavac D, Volavsek M, Pirtosek Z, Vizjak A, 2007, Light chain deposition disease restricted to the brain: the first case report. Hum Pathol 38:179–184
Piard F, Yaziji N, Jarry O, Assem M, Martin L, Bernard A et al, 1998, Solitary plasmacytoma of the lung with light chain extracellular deposits: a case report and review of the literature. Histopathol 32:356–361
Rostagno A, Frizzera G, Ylagan L, Kumar A, Ghiso J, Gallo G, 2002, Tumoral non-amyloidotic monoclonal immunoglobulin light chain deposits, ‘aggregoma’): presenting feature of B-cell dyscrasia in three cases with immunohistochemical and biochemical analyses. Br J Haematol 119:62–69
Bellotti V, Merlini G, 1996, Toward understanding the molecular pathogenesis of monoclonal immunoglobulin light-chain deposition. Nephrol Dial Transplant 11:1708–1711
Randall RE, Williamson WC Jr, Mullinax F, Tung NY, Still WJ, 1976, Manifestations of systemic light chain deposition. Am J Med 60:293–299
Buxbaum JN, Genega EM, Lazowski P, Kumar A, Tunick PA, Kronzon I et al, 2000, Infiltrative nonamyloidotic monoclonal immunoglobulin light chain cardiomyopathy: an underappreciated manifestation of plasma cell dyscrasias. Cardiology 93:220–228
Toor AA, Ramdane BA, Joseph J, Thomas M, O’Hara C, Barlogie B et al, 2006, Cardiac nonamyloidotic immunoglobulin deposition disease. Mod Pathol 19:233–237
Rivest C, Turgeon PP, Senecal JL, 1993, Lambda light chain deposition disease presenting as an amyloid-like arthropathy. J Rheumatol 20:880–884
Bhargava P, Rushin JM, Rusnock EJ, Hefter LG, Franks TJ, Sabnis SG et al, 2007, Pulmonary light chain deposition disease: report of five cases and review of the literature. Am J Surg Pathol 31:267–276
Colombat M, Mal H, Copie-Bergman C, Diebold J, Damotte D, Callard P et al, 2008, Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor. Blood 112:2004– 2012
Khoor A, Myers JL, Tazelaar HD, Kurtin PJ, 2004, Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases. Am J Clin Pathol 121:200–204
Weichman K, Dember LM, Prokaeva T, Wright DG, Quillen K, Rosenzweig M et al, 2006, Clinical and molecular characteristics of patients with non-amyloid light chain deposition disorders, and outcome following treatment with high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant 38:339–343
Lorenz EC, Gertz MA, Fervenza FC, Dispenzieri A, Lacy MQ, Hayman SR et al, 2008, Long-term outcome of autologous stem cell transplantation in light chain deposition disease. Nephrol Dial Transplant 23:2052–2057
Dores GM, Landgren O, McGlynn KA, Curtis RE, Linet MS, Devesa SS, 2009, Plasmacytoma of bone, extramedullary plasmacytoma, and multiple myeloma: incidence and survival in the United States, 1992–2004. Br J Haematol 144:86–94
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 249
EP 252
DI 10.1007/s12253-009-9218-1
PG 4
ER
PT J
AU Zhang, LY
Jiang, LN
Li, FF
Li, H
Liu, F
Gu, Y
Song, Y
Zhang, F
Ye, J
Li, Q
AF Zhang, Li-Ying
Jiang, Li-Na
Li, Fan-Fan
Li, Hang
Liu, Fang
Gu, Yu
Song, Yue
Zhang, Feng
Ye, Jing
Li, Qing
TI Reduced β-catenin Expression is Associated with Good Prognosis in Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Astrocytoma; β-catenin; Prognosis; Immunohistochemistry
ID Astrocytoma; β-catenin; Prognosis; Immunohistochemistry
AB The aim of this study was to evaluate the expression of β-catenin in astrocytoma, and the clinical relevance and prognostic significance of the expression of β-catenin was also analyzed. Immunohistochemistry was performed on 63 resected astrocytoma tumor specimens to detect the expression of β-catenin. The correlation between the results of immuoexpression and the clinicopathologic parameters and patient survival was processed statistically. In 63 samples of astrocytoma, 36 cases were immunoreactive for β-catenin at cytoplasm, ten cases of astrocytoma were immunoreactive at cytomembrane, and four cases of astrocytoma were stained for β-catenin at nucleus. Spearman analysis showed that the distribution of β-catenin was not correlated with the grades of astrocytoma. However, the expression profiles were correlated with the patient’s 2-year survival, but not correlated with the grades, tumor size, sex, age, or tumor location. Patients with low β-catenin expression levels tended to be associated with a better prognosis than those who with high levels (p=0.042). Our results suggest that β-catenin is useful for the prognosis evaluation of astrocytoma.
C1 [Zhang, Li-Ying] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Jiang, Li-Na] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Li, Fan-Fan] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Li, Hang] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Liu, Fang] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Gu, Yu] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Song, Yue] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Zhang, Feng] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Ye, Jing] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
[Li, Qing] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
RP Li, Q (reprint author), Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
EM liqing@fmmu.edu.cn
CR Louis DN, 1997, A molecular genetic model of astrocytoma histopathology. Brain Pathol 7:755–764
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Utsuki S, Sato Y, Oka H et al, 2002, Relationship between the expression of E-, N-cadherins and beta-catenin and tumor grade in astrocytomas. J Neurooncol 57:187–192
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Polakis P, 2000, Wnt signaling and cancer. Genes Dev 14:1837– 1851
Morin PJ, 1999, beta-catenin signaling and cancer. Bioessays 21:1021–1030
Wijnhoven BP, Dinjens WN, Pignatelli M, 2000, E-cadherincatenin cell-cell adhesion complex and human cancer. Br J Surg 87:992–1005
Woo DK, Kim HS, Lee HS et al, 2001, Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines. Int J Cancer 95:108–113
Grabsch H, Takeno S, Noguchi T et al, 2001, Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome. Histopathology 39:141–149
Zeng JZ, Hui Z, Rao HL, Zhang M, Hou J, Hui W, Qiu L, 2004, Expression of cytoskeleton proteins α- and β-catenin in gliomas. China Cancer 11:0738–0740
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 253
EP 257
DI 10.1007/s12253-009-9219-0
PG 5
ER
PT J
AU Li, M
Gu, Y
Zhang, Z
Zhang, Sh
Zhang, D
Saleem, FA
Zhao, X
Sun, B
AF Li, Man
Gu, Yanjun
Zhang, Zhiguang
Zhang, Shiwu
Zhang, Danfang
Saleem, F Ali
Zhao, Xiulan
Sun, Baocun
TI Vasculogenic Mimicry: a New Prognostic Sign of Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric adenocarcinoma; Hypoxia-inducible factor 1α; Microvascular density; Poorly differentiated; Tissue array; Vasculogenic mimicry
ID Gastric adenocarcinoma; Hypoxia-inducible factor 1α; Microvascular density; Poorly differentiated; Tissue array; Vasculogenic mimicry
AB Vasculogenic mimicry (VM) has been generally recognized as a new pattern of tumor neovascularization. It presents in many human malignancies. Till now, there is no report about VM in gastric adenocarcinoma (GAC). In this study, we collected 173 paraffinembedded human GAC samples, with detailed follow-up and clinicopathologic data. CD31/ periodic acid-Schiff (PAS) double staining, immunohistochemical staining of CK8 & 18 and laminin were performed to validate the existence of VM in GAC. Microvascular density (MVD) and vasulogenic mimicry density (VMD) were counted respectively. VM was observed in 40 of the 173 GAC patients, especially in poorly differentiated GAC (P=0.014). Patients with VM were prone to hematogenous metastasis and distant recurrence compared with patients without VM (P=0.020, 0.029). Higher VMD values was also associated with hematogenous metastasis (P=0.003). Immunohistochemical staining index (SI) of hypoxiainducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 were compared between the VM and non-VM group. The SI of four factors were all higher in the VM group than those of non-VM group (P=0.000, 0.000, 0.004, 0.009, respectively). The Kaplan-Meier survival analysis showed that the VM group has shorter life span compared with non-VM group (P=0.022). Cox proportional hazards model indicated that the presence of VM and TNM stage were independent predictors of poor prognosis (P=0.039 and 0.004) for GAC. In conclusion, VM exists in GAC, especially in poorly differentiated GAC. Additionally, it is an unfavorable prognostic indictor for GAC. Hypoxia may play a role in VM formation in GAC.
C1 [Li, Man] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Gu, Yanjun] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Zhang, Zhiguang] The Second Hospital of Tianjin Medical University, Department of Digestive, 300211 Tianjin, China.
[Zhang, Shiwu] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Zhang, Danfang] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Saleem, F Ali] Tianjin Medical University, Department of Surgery, 300060 Tianjin, China.
[Zhao, Xiulan] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Sun, Baocun] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
RP Sun, B (reprint author), Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
EM baocunsun@eyou.com
CR Maniotis AJ, Folberg R, Hess A et al, 1999, Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752
Chang YS, di Tomaso E, McDonald DM et al, 2000, Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA 97:14608–14613
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Liu C, Huang H, Donate F et al, 2002, Prostate-specific membrane antigen directed selective thrombotic infarction of tumors. Cancer Res 62:5470–5475
Shirakawa K, Tsuda H, Heike Y et al, 2001, Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Res 61:445– 451
Sun B, Zhang S, Zhang D et al, 2006, Vasculogenic mimicry is associated with high tumor grade, invasion and metastasis, and short survival in patients with hepatocellular carcinoma. Oncol Rep 16:693–698
Sun B, Zhang S, Zhao X et al, 2004, Vasculogenic mimicry is associated with poor survival in patients with mesothelial sarcomas and alveolar rhabdomyosarcomas. Int J Oncol 25:1609–1614
van der Schaft DW, Hillen F, Pauwels P et al, 2005, Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia. Cancer Res 65:11520–11528
Sun B, Qie S, Zhang S et al, 2008, Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors. Hum Pathol 39:846–856
Folberg R, Maniotis AJ, 2004, Vasculogenic mimicry. APMIS 112:508–525
Shirakawa K, Wakasugi H, Heike Y et al, 2002, Vasculogenic mimicry and pseudo-comedo formation in breast cancer. Int J Cancer 99:821–828
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Tanigawa N, Amaya H, Matsumura M et al, 1996, Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res 56:2671–2676
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Hasan J, Byers R, Jayson GC, 2002, Intra-tumoural microvessel density in human solid tumours. Br J Cancer 86:1566–1577
Issam Beyrouti M, Beyrouti R, Ben Amar M et al, 2007, Linitis plastica. Presse Med 36:1782–1786
Sood AK, Fletcher MS, Coffin JE et al, 2004, Functional role of matrix metalloproteinases in ovarian tumor cell plasticity. Am J Obstet Gynecol 190:899–909
Hendrix MJ, Seftor EA, Kirschmann DA et al, 2003, Remodeling of the microenvironment by aggressive melanoma tumor cells. Ann N Y Acad Sci 995:151–161
Hess AR, Seftor EA, Seftor RE et al, 2003, Phosphoinositide 3- kinase regulates membrane type 1-matrix metalloproteinase, MMP, and MMP-2 activity during melanoma cell vasculogenic mimicry. Cancer Res 63:4757–4762
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Cabuk D, Basaran G, Celikel C et al, 2007, Vascular endothelial growth factor, hypoxia-inducible factor 1a and CD34 expressions in early-stage gastric tumors: relationship with pathological factors and prognostic impact on survival. Oncology 72:111–117
Mizokami K, Kakeji Y, Oda S et al, 2006, Clinicopathologic significance of hypoxia-inducible factor 1a overexpression in gastric carcinomas. J Surg Oncol 94:149–154
Griffiths EA, Pritchard SA, Welch IM et al, 2005, Is the hypoxiainducible factor pathway important in gastric cancer? Eur J Cancer 41:2792–2805
Zhang J, Gao Q, 2008, Morphology and mechanism research of gastric cancer vasculogenic mimicry. Journal of Chongqing Medical University 33:1063–1066
Park SH, Han JK, Kim TK et al, 1999, Unusual gastric tumors: radiologic-pathologic correlation. Radiographics 19:1435–1446
Kunisaki C, Akiyama H, Nomura M et al, 2006, Clinicopathologic properties of poorly-differentiated adenocarcinoma of the stomach: comparison of solid- and non-solid-types. Anticancer Res 26:639–646
Adachi Y, Yasuda K, Inomata M et al, 2000, Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 89:1418–1424
Strosberg JR, Nasir A, Hodul P et al, 2008, Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res 2:113–125
Sood AK, Fletcher MS, Hendrix MJ, 2002, The embryonic-like properties of aggressive human tumor cells. J Soc Gynecol Investig 9:2–9
Hanahan D, Weinberg RA, 2000, The hallmarks of cancer. Cell 100:57–70
Kim SJ, Rabbani ZN, Dewhirst MW et al, 2005, Expression of HIF-1α CA IX, VEGF, and MMP-9 in surgically resected nonsmall cell lung cancer. Lung Cancer 49:325–335
Malemud CJ, 2006, Matrix metalloproteinases, MMPs, in health and disease: an overview. Front Biosci 11:1696–1701
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 259
EP 266
DI 10.1007/s12253-009-9220-7
PG 8
ER
PT J
AU Giaginis, C
Tsourouflis, G
Zizi-Serbetzoglou, A
Kouraklis, G
Chatzopoulou, E
Dimakopoulou, K
Theocharis, ES
AF Giaginis, Constantinos
Tsourouflis, Gerasimos
Zizi-Serbetzoglou, Adamantia
Kouraklis, Gregorios
Chatzopoulou, Elli
Dimakopoulou, Konstantina
Theocharis, E Stamatios
TI Clinical Significance of Ephrin (Eph)-A1, -A2, -A4, -A5 and -A7 Receptors in Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ephrins; Clinical significance; Clinicopathological parameters; Immunohistochemistry; Pancreatic adenocarcinoma; Prognostic marker
ID Ephrins; Clinical significance; Clinicopathological parameters; Immunohistochemistry; Pancreatic adenocarcinoma; Prognostic marker
AB Ephrin (Eph) receptors have been reported to be frequently overexpressed in a wide variety of cancer types, being associated with tumor growth, invasion, metastasis and angiogenesis. The aim of the present study was to evaluate the clinical significance of Eph-A1, -A2, -A4, -A5 and -A7 expression in pancreatic ductal adenocarcinoma. Eph-A1, -A2, -A4, -A5 and -A7 expression and staining intensity were assessed immunohistochemically in tumoral samples of 67 pancreatic adenocarcinoma patients and were statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity and patients’ survival. Eph receptors were abundantly expressed in pancreatic ductal adenocarcinoma cases examined. Eph-A1 staining intensity was significantly associated with tumor size (pT, p=0.008) and tumor histopathological stage (pStage, p=0.012). Eph-A2 expression was significantly associated with patients’ age (p=0.007), while Eph-A4 and Eph-A5 with tumor proliferative capacity (p=0.019 and p=0.011, respectively). Pancreatic adenocarcinoma patients with moderate/intense Eph-A5 or Eph-A7 staining presented significantly shorter survival times compared to those with negative/mild one (log-rank test, p=0.024 and p=0.009, respectively). Multivariate analysis identified Eph-A5 and Eph-A7 staining intensity as independent prognostic factors (p=0.048 and p=0.004, respectively). In conclusion, the present study revealed that Eph receptors were associated with pancreatic cancer characteristics, supporting evidence for their potential clinical application in management and prognosis of pancreatic adenocarcinoma patients.
C1 [Giaginis, Constantinos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias str, 11527 Athens, Greece.
[Tsourouflis, Gerasimos] University of Athens, Laikon Hospital, Second Department of Propedeutic Surgery, 17, Agiou Thoma str, 11527 Athens, Greece.
[Zizi-Serbetzoglou, Adamantia] Tzaneio General Hospital, Department of Pathology, Zanni & Afentouli str, 18536 Piraeus, Greece.
[Kouraklis, Gregorios] University of Athens, Laikon Hospital, Second Department of Propedeutic Surgery, 17, Agiou Thoma str, 11527 Athens, Greece.
[Chatzopoulou, Elli] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias str, 11527 Athens, Greece.
[Dimakopoulou, Konstantina] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias str, 11527 Athens, Greece.
[Theocharis, E Stamatios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias str, 11527 Athens, Greece.
RP Theocharis, ES (reprint author), University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 11527 Athens, Greece.
EM theocharis@ath.forthnet.gr
CR Zhang J, Hughes SE, 2006, Role of the ephrin and Ephrin receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system. J Pathol 208:453–461
Pasquale EB, 2008, Eph-ephrin bidirectional signaling in physiology and disease. Cell 133:38–52
Nakamoto M, Bergemann AD, 2002, Diverse role for the Eph family of receptor tyrosine kinases in carcinogenesis. Microscopy Res Technique 59:58–67
Surawska H, Ma PC, Salgia R, 2004, The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev 15:419–433
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 267
EP 276
DI 10.1007/s12253-009-9221-6
PG 10
ER
PT J
AU Luo, P
Wang, N
He, E
Eriksson, S
Zhou, J
Hu, G
Zhang, J
Skog, S
AF Luo, Pengcheng
Wang, Naining
He, Ellen
Eriksson, Staffan
Zhou, Ji
Hu, Guozhu
Zhang, Jie
Skog, Sven
TI The Proliferation Marker Thymidine Kinase 1 Level is High in Normal Kidney Tubule Cells Compared to other Normal and Malignant Renal Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kidney; Renal cell carcinoma; Thymidine kinase 1; TK1; Ki-67
ID Kidney; Renal cell carcinoma; Thymidine kinase 1; TK1; Ki-67
AB The activity of the proliferation related enzyme thymidine kinase 1 (TK1) was reported to be 3-fold higher in extracts from normal kidney tissue as compare to renal carcinoma extracts [3]. To verify these unexpected results, determinations of the protein levels of TK1 in normal kidney and in samples from different types of renal cell carcinoma (RCC) were done with immunohistochemistry and Western blot analysis. Two anti-TK1 peptide antibodies reacting with different TK1 epitops were used. TK1 levels were high in tubule cells as compared to glomerulus cells and connective tissue cells, while an intermediary TK1 was observed in renal cell carcinoma (RCC) cells. Western blot analysis demonstrated high levels of TK1 in extract from normal kidney, and lower levels of TK1 in the RCC extracts. The specificity of TK1 staining was demonstrated in competition experiments with excess TK1 antigen. The high TK1 levels in normal kidney tubule cells suggest that they are in a form of activated G1-state. The relatively low TK1 level in RCC, representing TK1 expression in S-phase cells, is in accordance with the low overall proliferation rate of these tumors. These results suggest that cell cycle regulation of TK1 in normal tubule cells differ from that in other type of normal and malignant renal cells.
C1 [Luo, Pengcheng] Renmin Hospital of Wuhan University, Department of NephrologyWuhan, China.
[Wang, Naining] Karolinska University, Department of Pathology, 141 86 Stockholm, Sweden.
[He, Ellen] Karolinska University Hospital, Department of Oncology, 141 86 Stockholm, Sweden.
[Eriksson, Staffan] Biomedical Center, Swedish University of Agricultural Science, Department of Anatomy, Physiology & Biochemistry, 751 23 Uppsala, Sweden.
[Zhou, Ji] Sino-Swed Molecular Bio-Medicine Research InstituteShenzhen, China.
[Hu, Guozhu] Jiangxi People´s Hospital, Department of Central LaboratoryNanchang, China.
[Zhang, Jie] Wuhan University, Renmin Hospital, Department of Urology, 238 Ziyang Road, 430060 Wuhan, Hubie Province, China.
[Skog, Sven] Karolinska University Hospital, Department of Oncology, 141 86 Stockholm, Sweden.
RP Zhang, J (reprint author), Wuhan University, Renmin Hospital, Department of Urology, 430060 Wuhan, China.
EM zhangjie888@sina.com
CR Rylova SN, Mirzaee S, Albertioni F, Eriksson S, 2007, Expression of deoxynucleoside kinases and 5′-nucleotidases in mouse tissues: implications for mitochondrial toxicity. Biochem Pharmacol 74:169–75
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 277
EP 283
DI 10.1007/s12253-009-9222-5
PG 7
ER
PT J
AU Schunemann, PD
Grivicich, I
Regner, A
Leal, FL
de Araujo, RD
Jotz, PG
Fedrigo, AC
Simon, D
da Rocha, BA
AF Schunemann, Pretto Daniel
Grivicich, Ivana
Regner, Andrea
Leal, Freitas Lisiane
de Araujo, Romani Daniela
Jotz, Pereira Geraldo
Fedrigo, Alexandre Carlos
Simon, Daniel
da Rocha, Brondani Adriana
TI Glutamate Promotes Cell Growth by EGFR Signaling on U-87MG Human Glioblastoma Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma multiforme; Glutamate; EGFR; Phospho-Akt; Cell proliferation
ID Glioblastoma multiforme; Glutamate; EGFR; Phospho-Akt; Cell proliferation
AB Accumulating evidences suggest that glutamate plays a key role in the proliferation and invasion of malignant glioblastoma (GBM) tumors. It has been shown that GBM cells release and exploit glutamate for proliferation and invasion through AMPA glutamate receptors. Additionally, amplification of the epidermal growth factor receptor (EGFR) gene occurs in 40–50% of GBM. Since, PI3K/Akt is considered one of the main intracellular pathways involved in EGFR activation, AKT functions could trigger EGFR signaling. Thus, we investigated whether EGFR-phospho-Akt pathway is involved on the glutamate inducing U-87MG human GBM cell line proliferation. For these purpose, we treated the U-87MG cell line with 5 to 200 mM of glutamate and assessed the number of viable cells by trypan blue dye exclusion test. An increase in cell number (50%) was found at 5 mM glutamate, while the addition of DNQX (500 μM), an antagonist of AMPA receptor, inhibited the effect of glutamate on the U87-MG cells proliferation. Also, at 5 mM glutamate we observed an increase on the EGFR and phospho-Akt contents evaluated by immunohistochemistry. Moreover, U-87MG cells treated with glutamate exhibited an increase about 2 times in the EGFR mRNA expression. While, in the presence of the anti-EGFR gefitinib (50 μM) or the PI3K inhibitor wortmannin (5 μM), the U-87MG proliferation was restored to control levels. Together, our data suggest that glutamate signaling mediated by AMPA receptor induces U-87MG human GBM cell line proliferation via EGFR-phospho-Akt pathway.
C1 [Schunemann, Pretto Daniel] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[Grivicich, Ivana] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[Regner, Andrea] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[Leal, Freitas Lisiane] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[de Araujo, Romani Daniela] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[Jotz, Pereira Geraldo] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e Molecular, Av Farroupilha, 8001, Predio 22, 5° andar, 92245-900 Canoas, RS, Brazil.
[Fedrigo, Alexandre Carlos] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
[Simon, Daniel] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e Molecular, Av Farroupilha, 8001, Predio 22, 5° andar, 92245-900 Canoas, RS, Brazil.
[da Rocha, Brondani Adriana] Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias MedicasCanoas, RS, Brazil.
RP da Rocha, BA (reprint author), Universidade Luterana do Brasil, Centro de Pesquisas em Ciencias Medicas, Canoas, Brazil.
EM brondani@terra.com.br
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2010
VL 16
IS 2
BP 285
EP 293
DI 10.1007/s12253-009-9223-4
PG 9
ER
PT J
AU Medinger, M
Kleinschmidt, M
Mross, K
Wehmeyer, B
Unger, C
Schaefer, HE
Weber, R
Azemar, M
AF Medinger, Michael
Kleinschmidt, Manuela
Mross, Klaus
Wehmeyer, Barbara
Unger, Clemens
Schaefer, Hans-Eckart
Weber, Renate
Azemar, Marc
TI c-kit (CD117) Expression in Human Tumors and its Prognostic Value: An Immunohistochemical Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-kit; Imatinib; Immunohistochemistry; Prognosis; Solid tumors; Tyrosine kinases
ID c-kit; Imatinib; Immunohistochemistry; Prognosis; Solid tumors; Tyrosine kinases
AB c-kit functions as a tyrosine kinase receptor and represents a target for small molecule kinase inhibitors. The expression pattern for c-kit was studied in different human tumor types to their correlation with prognosis. Paraffinembedded tumor tissues from 282 patients were analyzed immunohistochemically for c-kit expression. Survival and follow-up data were available from 192/282 (68%) patients. c-kit immunopositivity was found in 62/282 (22%) cases. ckit expression was found in 14/83 (17%) colorectal cancers, in 13/62 (21%) breast cancers, in 7/20 sarcomas (35%), in 5/14 (36%) renal cell carcinomas, in 2/12 ovarian cancers (17%) and in 2/12 (17%) hepatocellular carcinomas. We found no significant correlation between c-kit expression and prognosis although a trend to a worse prognosis in patients with c-kit positive tumors could be observed. Expression of c-kit was found in tumor samples with varying intensities and infrequently.
C1 [Medinger, Michael] Albert-Ludwigs University Freiburg, Tumor Biology CenterFreiburg im Breisgau, Germany.
[Kleinschmidt, Manuela] Albert-Ludwigs University Freiburg, Institute of PathologyFreiburg im Breisgau, Germany.
[Mross, Klaus] Albert-Ludwigs University Freiburg, Tumor Biology CenterFreiburg im Breisgau, Germany.
[Wehmeyer, Barbara] Novartis AGNurnberg, Germany.
[Unger, Clemens] Albert-Ludwigs University Freiburg, Tumor Biology CenterFreiburg im Breisgau, Germany.
[Schaefer, Hans-Eckart] Albert-Ludwigs University Freiburg, Institute of PathologyFreiburg im Breisgau, Germany.
[Weber, Renate] Internal Medicine, Munchnerstr. 14, 86163 Augsburg, Germany.
[Azemar, Marc] Albert-Ludwigs University Freiburg, Tumor Biology CenterFreiburg im Breisgau, Germany.
RP Medinger, M (reprint author), Albert-Ludwigs University Freiburg, Tumor Biology Center, Freiburg im Breisgau, Germany.
EM MedingerM@uhbs.ch
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 295
EP 301
DI 10.1007/s12253-010-9247-9
PG 7
ER
PT J
AU Ladanyi, A
Mohos, A
Somlai, B
Liszkay, G
Gilde, K
Fejos, Zs
Gaudi, I
Timar, J
AF Ladanyi, Andrea
Mohos, Anita
Somlai, Beata
Liszkay, Gabriella
Gilde, Katalin
Fejos, Zsuzsanna
Gaudi, Istvan
Timar, Jozsef
TI FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FOXP3; Immunohistochemistry; Melanoma; Prognosis; Regulatory T cell
ID FOXP3; Immunohistochemistry; Melanoma; Prognosis; Regulatory T cell
AB Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4+CD25+ Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3+ cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3+ cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3+ lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.
C1 [Ladanyi, Andrea] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, 7–9. Rath Gyorgy u, 1122 Budapest, Hungary.
[Mohos, Anita] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Gilde, Katalin] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Fejos, Zsuzsanna] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Gaudi, Istvan] National Institute of Oncology, National Cancer RegistryBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Ladanyi, A (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, 1122 Budapest, Hungary.
EM ladanyi@oncol.hu
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Hiraoka N, Onozato K, Kosuge T, Hirohashi S, 2006, Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12:5423–5434
Bates GJ, Fox SB, Han C et al, 2006, Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24:5373–5380
Kobayashi N, Hiraoka N, Yamagami W et al, 2007, FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res 13:902–911
Gao Q, Qiu S-J, Fan J et al, 2007, Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25:2586–2593
Fox SB, Launchbury R, Bates GJ et al, 2007, The number of regulatory T cells in prostate cancer is associated with the androgen receptor and hypoxia-inducible factor, HIF)-2α but not HIF-1α. Prostate 67:623–629
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Badoual C, Hans S, Rodriguez J et al, 2006, Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancer. Clin Cancer Res 12:465–472
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Carreras J, Lopez-Guillermo A, Fox BC et al, 2006, High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood 108:2957–2964
Gjerdrum LM, Woetmann A, Odum N et al, 2007, FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival. Leukemia 21:2512–2518
Lee NR, Song EK, Jang KY et al, 2008, Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma 49:247–256
Mourmouras V, Fimiani M, Rubegni P et al, 2007, Evaluation of tumour-infiltrating CD4+CD25+FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases. Br J Dermatopathol 157:531–539
De Panfilis G, Campanini N, Santini M et al, 2008, Phase- and stage-related proportions of T cells bearing the transcription factor FOXP3 infiltrate primary melanoma. J Invest Dermatol 128:676– 684
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Kryczek I, Liu R, Wang G et al, 2009, FOXP3 defines regulatory T cells in human tumor and autoimmune disease. Cancer Res 69:3995–4000
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 303
EP 309
DI 10.1007/s12253-010-9254-x
PG 7
ER
PT J
AU Wincewicz, A
Koda, M
Sulkowski, S
Kanczuga-Koda, L
Sulkowska, M
AF Wincewicz, Andrzej
Koda, Mariusz
Sulkowski, Stanislaw
Kanczuga-Koda, Luiza
Sulkowska, Mariola
TI Comparison of Beta-catenin with TGF-beta1, HIF-1alpha and Patients’ Disease-free Survival in Human Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Beta-catenin; TGF-beta1; HIF-1alpha; Patients’ disease free survival; Colorectal cancer
ID Beta-catenin; TGF-beta1; HIF-1alpha; Patients’ disease free survival; Colorectal cancer
AB Beta-catenin accumulation is suppressed by TGFbeta1 (transforming growth factor beta1) in intestinal epithelium suggesting negative feedback between these two factors. Besides that, beta-catenin interacts with HIF-1alpha (hypoxiainducible factor-1alpha) at the promoter region of HIF-1 target genes. Our study was aimed at comparison of beta-catenin with HIF-1alpha, TGF-beta1, Ki67 and survival of sporadic colorectal cancer patients. Expressions of beta-catenin, TGFbeta1, HIF-1alpha, Ki67 were evaluated in triads of specimens of each primary tumor of 72 sporadic colorectal cancers with immunohistochemistry due to limited availability of tissue material. Disease-free survival was analyzed in case of all 100 beta-catenin stained tumors, in 85 cancers stained for HIF-1 and in 72 neoplasms with TGFbeta1 staining. Beta-catenin, TGF-beta1 and HIF-1alpha accumulated in 72 colorectal cancer cells. Beta-catenin correlated both with HIF-1alpha and TGF-beta1 in all colorectal cancers (p<0.009, r=0.307 and p=0.003, r=0.342, respectively) and in subgroups of different clinico-pathological profile. Beta-catenin failed to correlate with Ki67. In case of beta-catenin, TGF-beta1 and HIF-1alpha, disease-free survival curves failed to show any statistically significant differences between groups of marker negative tumors, cancers with low expression and neoplasms with higher protein expression. Positive correlations between beta-catenin and TGF-beta1 may indicate ineffective attempts of TGF-beta1 to reduce intracellular level of beta-catenin in colorectal cancer. Associations between beta-catenin and HIF-1alpha reflect previously detected interactions between HIF-1alpha with beta-catenin and are confirmative for presence of such reactions in human colorectal cancer.
C1 [Wincewicz, Andrzej] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Koda, Mariusz] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Sulkowski, Stanislaw] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Kanczuga-Koda, Luiza] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
[Sulkowska, Mariola] Medical University of Bialystok, Department of General Pathomorphology, Waszyngtona St 13, 15-269 Bialystok, Poland.
RP Wincewicz, A (reprint author), Medical University of Bialystok, Department of General Pathomorphology, 15-269 Bialystok, Poland.
EM andwinc@gmail.com;ruahpolin@yahoo.com
CR Wong NA, Pignatelli M, 2002, Beta-catenin-a linchpin in colorectal carcinogenesis? Am J Pathol 160:389–401
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 311
EP 318
DI 10.1007/s12253-009-9217-2
PG 8
ER
PT J
AU Guo, F
Liu, Y
Huang, J
Li, Y
Zhou, G
Wang, D
Li, Y
Wang, J
Xie, P
Li, G
AF Guo, Fengjie
Liu, Yan
Huang, Jian
Li, Yuehui
Zhou, Guohua
Wang, Di
Li, Yalin
Wang, Jiajia
Xie, Pingli
Li, Guancheng
TI Identification of Rho GTPase Activating Protein 6 Isoform 1 Variant as a New Molecular Marker in Human Colorectal Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RhoGAP6 isform 1 variant; Colorectal cancer; Mass spectrometry; Biomarker; Monoclonal antibody
ID RhoGAP6 isform 1 variant; Colorectal cancer; Mass spectrometry; Biomarker; Monoclonal antibody
AB The early diagnosis of colorectal cancer (CRC) is important because it is one of the most readily curable of all cancers, if detected early. However, the sensitivity of current markers is low. Immunostaining intensity for the monoclonal antibody Hb3 in CRC cell lines and tissues was stronger than in controls. Interestingly, this was associated with a low level of tumor differentiation. We used Hb3-coupled affinity chromatography to search for a corresponding Hb3 antigen as a candidate biomarker for early detection, and identified a Rho GTPase activating protein 6 (RhoGAP6) isoform 1 variant as an Hb3 antigen by mass spectrometry. Using reverse transcription polymerase chain reaction and western blot analysis, we confirmed that the expression levels of this variant were elevated in aberrant cells and tissues. Thus, the RhoGAP6 isoform 1 variant might serve as a biomarker for the development and progression of CRC.
C1 [Guo, Fengjie] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Liu, Yan] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Huang, Jian] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Li, Yuehui] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Zhou, Guohua] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Wang, Di] The First Hospital of Changsha, Department of PathologyChangsha, Hunan Province, China.
[Li, Yalin] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Wang, Jiajia] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Xie, Pingli] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
[Li, Guancheng] Central South University, Xiangya Medical School, Cancer Research Institute, 110 Xiangya Road, 410078 Changsha, Hunan Province, China.
RP Li, G (reprint author), Central South University, Xiangya Medical School, Cancer Research Institute, 410078 Changsha, China.
EM libsun@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 319
EP 326
DI 10.1007/s12253-009-9226-1
PG 8
ER
PT J
AU Habibollahi, P
Jamshidiha, M
Daryani, EN
Jahanzad, I
Ghahremani, HM
Ostad, NS
AF Habibollahi, Peiman
Jamshidiha, Mostafa
Daryani, E Nasser
Jahanzad, Issa
Ghahremani, H Mohammad
Ostad, Nasser Seyed
TI Correlation Between Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression in Human Colorectal Adenocarcinoma: A Cross-Sectional Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Nitric oxide synthase; Cyclooxygenase-2; Adenocarcinoma
ID Colorectal cancer; Nitric oxide synthase; Cyclooxygenase-2; Adenocarcinoma
AB Cyclooxygenase-2 (COX-2) enzyme is believed to play a role in tumor angiogenesis, differentiation, and apoptosis. The inducible isoform of nitric oxide synthase (iNOS) also has the potential ability to damage DNA and conceivably contribute to tumor formation by a rise in nitric oxide production. Seventeen patients diagnosed with colorectal adenocarcinoma, who underwent surgical resection of the tumor, were enrolled in the study. Two macroscopic tissue samples, one from the tumor and the other from the tumor free surgical margin were collected from every patient as formalin fixed paraffin embedded blocks. Samples were analyzed for iNOS and COX-2 expression by immunohistochemistry and Western blotting. Results were digitized and semi-quantitatively analyzed. Immunohistochemistry revealed a similar pattern of expression for both iNOS and COX-2, as both were detected in tumor and epithelial cells. The mean iNOS and COX-2 levels determined by Western blotting method were significantly higher in tumor than in the tumor-free tissues (Wilcoxon signed-rank test, p<0.001 both for iNOS and COX-2). Patients with lymph node involvement had higher levels of both enzymes in tumors (Mann-Whitney U test, p<0.05). There was correlation between iNOS and COX-2 expression of tumor determined by immunohistochemistry and also by Western blotting (Spearman’s rho test, R=0.53, p=0.03 and R=0.57, p=0.02, respectively). In conclusion, our results point out a relationship between iNOS and COX-2 expression in human colorectal adenocarcinomas and may also suggest a possible link between advanced stages of the disease and higher expression of iNOS and COX-2.
C1 [Habibollahi, Peiman] Tehran University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacology & ToxicologyTehran, Iran.
[Jamshidiha, Mostafa] Tehran University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacology & ToxicologyTehran, Iran.
[Daryani, E Nasser] Tehran University of Medical Sciences, Department of GastroenterologyTehran, Iran.
[Jahanzad, Issa] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Ghahremani, H Mohammad] Tehran University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacology & ToxicologyTehran, Iran.
[Ostad, Nasser Seyed] Tehran University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacology & ToxicologyTehran, Iran.
RP Ostad, NS (reprint author), Tehran University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacology & Toxicology, Tehran, Iran.
EM ostadnas@tums.ac.ir
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 327
EP 335
DI 10.1007/s12253-009-9239-9
PG 9
ER
PT J
AU Gisterek, I
Matkowski, R
Lacko, A
Sedlaczek, P
Szewczyk, K
Biecek, P
Halon, A
Staszek, U
Szelachowska, J
Pudelko, M
Bebenek, M
Harlozinska-Szmyrka, A
Kornafel, J
AF Gisterek, Iwona
Matkowski, Rafal
Lacko, Aleksandra
Sedlaczek, Pawel
Szewczyk, Krzysztof
Biecek, Przemyslaw
Halon, Agnieszka
Staszek, Urszula
Szelachowska, Jolanta
Pudelko, Marek
Bebenek, Marek
Harlozinska-Szmyrka, Antonina
Kornafel, Jan
TI Serum Vascular Endothelial Growth Factors A, C and D in Human Breast Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Vascular endothelial growth factor-A; Vascular endothelial growth factor-C; Vascular endothelial growth factor-D; Serum assay; Breast cancer
ID Vascular endothelial growth factor-A; Vascular endothelial growth factor-C; Vascular endothelial growth factor-D; Serum assay; Breast cancer
AB Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions. We found strong correlation between VEGF-A and VEGF-D and between VEGF- C and VEGF-D. Besides serum VEGF-D levels and estrogen receptor (ER) expressions no other correlations between VEGF and clinicopathologic variables were observed. However, elevated VEGF-A and VEGF-C concentrations were associated with increased number of erythrocytes, leukocytes and platelets. In Cox model values of angiogenic serum markers and recognized prognostic markers in breast cancer, VEGF-C turned out as independent prognostic factor. Our study is the first analysis showing correlation between serum concentrations of three angiogenic factors: VEGF-A, VEGF-C, VEGF-D. Associations between angiogenic cytokines and number of blood cells may be due to release of VEGF from platelets and leucocytes. Prognostic role of VEGF is still uncertain, though VEGF-C has a potential to serve as a prognostic marker.
C1 [Gisterek, Iwona] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Matkowski, Rafal] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Lacko, Aleksandra] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Sedlaczek, Pawel] Wroclaw Medical University, Department of Clinical ImmunologyWroclaw, Poland.
[Szewczyk, Krzysztof] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Biecek, Przemyslaw] University of Warsaw, Faculty of Mathematics, Informatics, and MechanicsWarsaw, Poland.
[Halon, Agnieszka] Wroclaw Medical University, Department of PathologyWroclaw, Poland.
[Staszek, Urszula] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Szelachowska, Jolanta] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Pudelko, Marek] Lower Silesian Oncology Center, Department of Oncological SurgeryWroclaw, Poland.
[Bebenek, Marek] Lower Silesian Oncology Center, Department of Oncological SurgeryWroclaw, Poland.
[Harlozinska-Szmyrka, Antonina] Wroclaw Medical University, Department of Clinical ImmunologyWroclaw, Poland.
[Kornafel, Jan] Wroclaw Medical University, Department of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
RP Matkowski, R (reprint author), Wroclaw Medical University, Department of Oncology, 53-413 Wroclaw, Poland.
EM matkowski.r@dco.com.pl
CR Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S, Sugimachi K, 2001, Clinical significance of vascular endothelial growth factor-C, VEGF-C, in breast cancer. Breast Cancer Res Treat 66:159–164
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Hefler L, Zeillinger R, Grimm C, Sood A, Cheng W, Gadducci A, Tempfer CB, Reinthaller A, 2006, Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer. Gynecol Oncol 103:512–517
Gonzalez F, Quesada A, Sevilla I, Baca F, Medina M, Amores J, Diaz JM, Rius-Diaz F, Marques E, Alba E, 2007, Prognostic value of serum angiogenic activity in colorectal cancer patients. J Cell Mol Med 11:120–128
De Vita F, Orditura M, Lieto E, Infusino S, Morgillo F, Martinelli E, Castellano P, Romano C, Ciardiello F, Catalano G, Pignatelli C, Galizia G, 2004, Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma. Cancer 100:270–278
Wang T, Deng M, Qiu W, Dong W, 2007, Association of serum vascular endothelial growth factor –C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer. World J Gastroenterol 13:1794–1798
Tamura M, Ohta Y, 2003, Serum vascular endothelial growth factor –C level in patients with primary nonsmall cell lung carcinoma. Cancer 98:1217–1222
Bando H, Weich H, Brokelmann M, Horiguchi S, Funata N, Ogawa T, Toi M, 2005, Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer. Br J Cancer 92:553–561
Foekens J, Peters H, Grabenchtchikov N, Look M, Meijer-van Gelder M, Geurts-Moespot A, van der Kwast TH, Sweep CG, Klijn JG, 2001, High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in breast cancer. Cancer Res 61:5407–541
Granato A, Frassineti G, Giovannini N, Ballardini M, Nanni O, Maltoni R, Amadori D, Volpi A, 2006, Do serum angiogenic growth factors provide additional information to that of conventional markers in monitoring the course of metastatic breast cancer? Tumor Biol 27:302–308
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Adams J, Carder P, Downey S, Forbes M, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ, Cairnduff F, Selby PJ, Perren TJ, Lansdown M, Banks RE, 2000, Vascular endothelial growth factor, VEGF, in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res 60:2898–2905
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Werther K, Christensen I, Nielsen H, 2002, Determination of vascular endothelial growth factor, VEGF, in circulating blood: significance of VEGF in various leucocytes and platelets. Scand J Clin Lab Invest 62:343–350
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 337
EP 344
DI 10.1007/s12253-009-9211-8
PG 8
ER
PT J
AU Watari, H
Kanuma, T
Ohta, Y
Hassan, KM
Mitamura, T
Hosaka, M
Minegishi, T
Sakuragi, N
AF Watari, Hidemichi
Kanuma, Tatsuya
Ohta, Yoko
Hassan, Kamel Mohamed
Mitamura, Takashi
Hosaka, Masayoshi
Minegishi, Takashi
Sakuragi, Noriaki
TI Clusterin Expression Inversely Correlates with Chemosensitivity and Predicts Poor Survival in Patients with Locally Advanced Cervical Cancer Treated with Cisplatin-Based Neoadjuvant Chemotherapy and Radical Hysterectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clusterin; Neoadjuvant chemotherapy; Cervical cancer; Lymphnode metastasis; Immunohistochemistry
ID Clusterin; Neoadjuvant chemotherapy; Cervical cancer; Lymphnode metastasis; Immunohistochemistry
AB Overexpression of clusterin, an antiapoptotic molecule, has been reported to induce resistance to chemotherapy in a variety of cancer cell types. The aim of this study was to evaluate the significance of clusterin expression to predict response to platinum-based neoadjuvant chemotherapy and survival of patients with invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy specimens of invasive cervical cancer before neoadjuvant chemotherapy were obtained from 46 patients who subsequently underwent radical hysterectomy at Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007. The expression of clusterin protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of clusterin protein in cervical cancer tissues before neoadjuvant chemotherapy was significantly related to poor response to chemotherapy among factors analyzed. Univariate analysis on prognostic factors showed that response to chemotherapy (p=0.01), lymph node metastasis (p=0.02), and clusterin expression (p=0.02) were related to survival. Multivariate analysis revealed that lymph node metastasis (p=0.03), and clusterin expression (p=0.03) were independent prognostic factors for survival of cervical cancer patients. We conclude that clusterin expression could be a new molecular marker to predict response to platinumbased chemotherapy and survival of patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy.
C1 [Watari, Hidemichi] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
[Kanuma, Tatsuya] Gunma University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 371-8511 Maebashi, Japan.
[Ohta, Yoko] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
[Hassan, Kamel Mohamed] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
[Mitamura, Takashi] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
[Hosaka, Masayoshi] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
[Minegishi, Takashi] Gunma University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 371-8511 Maebashi, Japan.
[Sakuragi, Noriaki] Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kita-Ku, 060-8638 Sapporo, Japan.
RP Watari, H (reprint author), Hokkaido University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 060-8638 Sapporo, Japan.
EM watarih@med.hokudai.ac.jp
CR Panici PB, Greggi S, Scambia G et al, 1998, Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Eur J Cancer 34:341–346
Redondo M, Villar E, Torres-Munoz J et al, 2002, Overexpression of clusterin in human breast carcinoma. Am J Pathol 157:393–399
Pucci S, Bonanno E, Pichiorri F et al, 2004, Modulation of different clusterin isoforms in human colon tumorigenesis. Oncogene 23:2298–2304
Chung J, Kwak C, Jin RJ et al, 2004, Enhanced chemosensitivity of bladder cancer cells to cisplatin by suppression of clusterin in vitro. Cancer Lett 203:155–161
Zellweger T, Chi K, Miyake H et al, 2002, Enhanced radiosensitivity in prostate cancer by inhibition of the cell survival protein clusterin. Clin Cancer Res 8:3276–3284
Miyake H, Hara S, Arakawa S et al, 2002, Overexpression of clusterin is an independent prognostic factor for nonpapillary renal cell carcinoma. J Urol 167:703–706
Kruger S, Ola V, Fisher D et al, 2007, Prognostic significance of clusterin immunoreactivity in breast cancer. Neoplasma 54:46– 50
Watari H, Ohta Y, Hassan MK et al, 2008, Clusterin expression predicts survival of invasive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy. Gynecol Oncol 108:527–532
Konishi I, Nanbu K, Mandai M et al, 1998, Tumor response to neoadjuvant chemotherapy correlates with the expression of Pglycoprotein and PCNA but not GST-pi in the tumor cells of cervical carcinoma. Gynecol Oncol 70:365–371
Faried LS, Faried A, Kanuma T et al, 2006, Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy. Oncol Rep 16:57–63
Saito T, Takehara M, Tanaka R et al, 2004, Correlation between responsiveness of neoadjuvant chemotherapy and apoptosisassociated proteins for cervical adenocarcinoma. Gynecol Oncol 92:284–292
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Ferrandina G, Lauriola L, Distefano MG et al, 2002, Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol 20:973–981
Chung HH, Kim MK, Kim JW et al, 2006, XRCC1 R399Q polymorphism is associated with response to platinum-based neoadjuvant chemotherapy in bulhy cervical cancer. Gynecol Oncol 103:1031–1037
Sowery RD, Hadaschik BA, So AI et al, 2008, Clusterin knockdown using the antisense oligonucleotide OGX-011 resensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy. BJU Int 102:389–397
Miyake H, Eto H, Hara I et al, 2004, Synergistic antitumor activity by combined treatment with gemcitabine and antisense oligodeoxynucleotide targeting clusterin gene in an intravesical administration model against human bladder cancer kotcc-1 cells. J Urol 171:2477–2481
Mizutani K, Matsumoto K, Hasegawa N et al, 2006, Expression of clusterin, XIAP and survivin, and their changes by camptothecin, CPT, treatment in CPT-resistant PC-3 and CPT-sensitive LNCaP cells. Exp Oncol 28:209–251
Lourda M, Trougakos P, Gonos ES, 2006, Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up-regulation of Clusterin/Apolipoprotein J. Int J Cancer 120:611–622
Park DC, Yeo SG, Shin EY et al, 2006, Custerin confers paclitaxel resistance in cervical cancer. Gynecol Oncol 103:996– 1000
Lahousen M, Haas J, Pockel H et al, 1999, Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: a randomized, prospective multicenter trial. Gynecol Oncol 73:196–201
Saad F, Hotte SJ, North S, et al, 2008, A phase II randomized study evaluating custirsen, OGX-011, in patients with hormone refractory prostate cancer, HRPC, who relapsed on or within 6 months of first-line docetaxel therapy. ASCO Genitourinary cancers symposium; abstract#151
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 345
EP 352
DI 10.1007/s12253-009-9235-0
PG 8
ER
PT J
AU Qin, F
Song, Y
Li, Z
Zhao, L
Zhang, Y
Geng, L
AF Qin, Fengjin
Song, Yao
Li, Zijian
Zhao, Ling
Zhang, Youyi
Geng, Li
TI S100A8/A9 Induces Apoptosis and Inhibits Metastasis of CasKi Human Cervical Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Cervical cancer; Metastasis; MMP-2; S100 proteins
ID Apoptosis; Cervical cancer; Metastasis; MMP-2; S100 proteins
AB S100 proteins, a family of Ca2+-binding proteins, have been linked to several human diseases in recent years. Deregulated expression of S100 proteins, including S100A9 and its partner S100A8, was reported to be associated with neoplastic disorders. In our previous study using serial analysis of gene expression, we identified decreased expressions of S100A9 and S100A8 in human cervical squamous cell carcinoma. To investigate the functions of S100A8 and S100A9 in cervical cancer, we purified recombinant S100A8 and S100A9 proteins and treated CaSki human cervical cancer cells with these proteins. We found that S100A8/A9 induced apoptosis and inhibited migration of CaSki cells; S100A8/A9 also reduced the expression of matrix metalloproteinase (MMP)-2 in CaSki cells. In summary, this study suggests that S100A8 and S100A9 have inhibitory effects on the proliferation of CaSki carcinoma cells by inducing cell apoptosis and on the invasiveness of CaSki cells.
C1 [Qin, Fengjin] Peking University Third Hospital, Department of Obstetrics and Gynecology, 100191 Beijing, China.
[Song, Yao] Ministry of Education, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Institute of Vascular Medicine, 100191 Beijing, China.
[Li, Zijian] Ministry of Education, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Institute of Vascular Medicine, 100191 Beijing, China.
[Zhao, Ling] Peking University Third Hospital, Department of Obstetrics and Gynecology, 100191 Beijing, China.
[Zhang, Youyi] Ministry of Education, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Institute of Vascular Medicine, 100191 Beijing, China.
[Geng, Li] Peking University Third Hospital, Department of Obstetrics and Gynecology, 100191 Beijing, China.
RP Geng, L (reprint author), Peking University Third Hospital, Department of Obstetrics and Gynecology, 100191 Beijing, China.
EM gengli57@163.com
CR Parkin DM, Bray F, Ferlay J et al, 2005, Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 353
EP 360
DI 10.1007/s12253-009-9225-2
PG 8
ER
PT J
AU Al-Attar, A
Shehata, M
Durrant, L
Moseley, P
Deen, S
Chan, S
AF Al-Attar, Ahmad
Shehata, Mohamed
Durrant, Lindy
Moseley, Paul
Deen, Suha
Chan, Stephen
TI T Cell Density and Location Can Influence the Prognosis of Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intra-tumoural T cells; Ovarian cancer; Prognosis; Stromal T cells
ID Intra-tumoural T cells; Ovarian cancer; Prognosis; Stromal T cells
AB The aims of this study were to examine the significance of CD3+ cells in patients with epithelial ovarian cancer and to determine their influence on the disease in relation to their location within tumours. A 157-core tissue-microarray constructed from primary ovarian cancer patients treated at Nottingham-University-Hospitals (2000–2007) was stained for the T-cell marker CD3. The number of CD3+ cells in direct contact with tumour cells was counted per tumour area. These were considered as "intra-tumoural T-cells (ITTC)". Cores were divided into CD3 'high' or 'low' density tumours. "Stromal T-cells (STC)" were assigned as 'positive' or 'negative'. The study population had a median follow-up time of 36-months (0– 75). The number of ITTC counted in tumour cores ranged between 0 and 184/mm2. 90-tumours-(57%) were found to be in the "low-density" rubric, while 56-(36%) were of a "high-density" T-cell population. STC were found in 118-cores-(75%)-compared to 22-cores-(14%)-negative cores. Higher number of ITTC correlated with lower-grade-(p=0.045), tumour-type-(p=0.034), and longer-median-survivaltimes (57-versus 37-months for high-and low-ITTC densities, respectively, p=0.038). This relationship was reversed when tumours were infiltrated by CD3+ cells in the stroma, predicting worse-survival (Log-rank-test, p=0.028). Combining ITTC with STC produced an interesting pattern where the ITTC-low/STC + ve had the worst prognosis (p=0.003). Infiltration of ovarian cancer by T-cells can influence its prognosis depending on the location of these cells (intratumoural-versus-stromal). The former predicts improved survival, while the latter is probably contributing to tumour progression and, in turn, worse survival.
C1 [Al-Attar, Ahmad] Nottingham University, Department of Clinical Oncology, Hospitals, NHS Trust–City Campus, Hucknall Road, NG5 1PB Nottingham, UK.
[Shehata, Mohamed] Nottingham University, Department of Clinical Oncology, Hospitals, NHS Trust–City Campus, Hucknall Road, NG5 1PB Nottingham, UK.
[Durrant, Lindy] University of Nottingham, Department of Academic Oncology, Hucknall Road, NG5 1PB Nottingham, UK.
[Moseley, Paul] Nottingham University, Department of Clinical Oncology, Hospitals, NHS Trust–City Campus, Hucknall Road, NG5 1PB Nottingham, UK.
[Deen, Suha] Nottingham University Hospitals, Department of Histopathology, NHS Trust–QMC Campus, Derby Road, NG7 2UH Nottingham, UK.
[Chan, Stephen] Nottingham University, Department of Clinical Oncology, Hospitals, NHS Trust–City Campus, Hucknall Road, NG5 1PB Nottingham, UK.
RP Chan, S (reprint author), Nottingham University, Department of Clinical Oncology, NG5 1PB Nottingham, UK.
EM steve.chan@nuh.nhs.uk
CR CRUK, 2009, UK Ovarian Cancer statistics [cited 2009 20/05/ 2009]; Available from:
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 361
EP 370
DI 10.1007/s12253-009-9230-5
PG 10
ER
PT J
AU Gunia, S
May, M
Koch, S
Dietel, M
Erbersdobler, A
AF Gunia, Sven
May, Matthias
Koch, Stefan
Dietel, Manfred
Erbersdobler, Andreas
TI MUC1 Expression in Incidental Prostate Cancer Predicts Staging and Grading on the Subsequent Radical Prostatectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Incidental prostate cancer; MUC1 (episialin); Immunohistochemistry; Histopathologic outcome parameters; Radical prostatectomy
ID Incidental prostate cancer; MUC1 (episialin); Immunohistochemistry; Histopathologic outcome parameters; Radical prostatectomy
AB The behavior of Incidental prostate cancer (IPC) cannot be reliably predicted by means of conventional histomorphology. MUC1 (episialin) expression has been linked to poor outcome in peripheral prostate cancer (PC). We aimed to determine the so far neglected prognostic role of MUC1 expression in IPC which most commonly represents transition zone cancer. Using Tissue microarray (TMA), we assessed the association between MUC1 expression recorded in transurethral resection specimens of the prostate (TURP chips) and histopathologic outcome parameters (Gleason scores and histologic staging) performed on the subsequent radical prostatectomies (RPs) in a study cohort of 54 patients. Due to tissue loss during arraying and sectioning, a total of 44 (81.5%) tumor samples remained available for immunostaining which was dichotomized by two independent clinical pathologists as being absent or present. MUC1 expression was present in 7 (15.9%) of the 44 IPC immunohistochemically investigated with a striking overrepresentation in high stage tumors, and was significantly correlated with histopathologic staging (ρ=0.4; p=0.02) and Gleason scores (ρ=0.3; p=0.03) performed on the corresponding RPs. These data were confirmed by means of the McNemar test (staging: p=0.01; grading: p=0.04). Our findings suggest that MUC1 might become a valuable adjunct to enable individual prognostic ramification prior to radical surgery in prostate cancer histologically detected in TURP chips. This interesting observation clearly awaits validation by larger studies surveying clinical follow-up data.
C1 [Gunia, Sven] Charite-University Medicine Teaching Hospital, Department of Pathology, Pieskower Straße 33, 15526 Bad Saarow, Germany.
[May, Matthias] Klinikum St. Elisabeth, Department of UrologyStraubing, Germany.
[Koch, Stefan] Charite-University Medicine Teaching Hospital, Department of Pathology, Pieskower Straße 33, 15526 Bad Saarow, Germany.
[Dietel, Manfred] Charite University Hospital, Institute of Pathology, Campus Charite MitteBerlin, Germany.
[Erbersdobler, Andreas] Charite University Hospital, Institute of Pathology, Campus Charite MitteBerlin, Germany.
RP Gunia, S (reprint author), Charite-University Medicine Teaching Hospital, Department of Pathology, 15526 Bad Saarow, Germany.
EM sven.gunia@helios-kliniken.de
CR Van Andel G, Vleeming R, Kurth KH, de Reijke TM, 1995, Incidental carcinoma of the prostate. Semin Surg Oncol 11:36–45
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Melchior S, Hadaschik B, Thuroff S, Thomas C, Gillitzer R, Thuroff J, 2008, Outcome of radical prostatectomy for incidental carcinoma of the prostate. BJU Int Dec 5 [Epub ahead of print]
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Garbar C, Mascaux C, Wespes E, 2008, Expression of MUC1 and sialyl-Tn in benign prostatic glands, high-grade prostate intraepithelial neoplasia and malignant prostatic glands: a preliminary study. Anal Quant Cytol Histol 30:71–77
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Strawbridge RJ, Nister M, Brismar K, Li C, Lindstrom S, 2008, Influence of MUC1 genetic variation on prostate cancer risk and survival. Eur J Hum Genet 16:1521–1525
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Gunia S,Koch S,May M, Dietel M, ErbersdoblerA(2009, Expression of prostatic acid phosphatase, PSAP, in transurethral resection specimens of the prostate is predictive of histopathologic tumor stage in subsequent radical prostetctomies. Virchows Arch 454:573–579
Morrison C, Merati K,MarshWL Jr, De Lott L, Cohn DE, Young G, Frankel WL, 2007, The mucin expression profile of endometrial carcinoma and correlation with clinical-pathologic parameters. Appl Immunohistochem Mol Morphol 15:426–431
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 371
EP 375
DI 10.1007/s12253-009-9231-4
PG 5
ER
PT J
AU Smuk, G
Illes,
Keresztes, K
Kereskai, L
Marton, B
Nagy, Zs
Lacza,
Pajor, L
AF Smuk, Gabor
Illes, Arpad
Keresztes, Katalin
Kereskai, Laszlo
Marton, Balazs
Nagy, Zsofia
Lacza, Agnes
Pajor, Laszlo
TI Pheno- and Genotypic Features of Epstein-Barr Virus Associated B-Cell Lymphoproliferations in Peripheral T-Cell Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B-cell lymphoproliferation; Epstein-Barr virus; T-cell lymphoma
ID B-cell lymphoproliferation; Epstein-Barr virus; T-cell lymphoma
AB Among the 300 peripheral T-cell lymphomas (PTCL) searched for EBV positive non-resting B-cells by EBER in situ hybridization 12 have been identified with various forms of EBV-driven B-cell proliferation. This could be categorized into three major forms. i. In the first form scattered immature, mononuclear B-cells of immuno-, centroblastic type with CD20+. CD30+ CD45+, LMP1+ phenotype, reactive appearance and polyclonal immunoglobulin heavy chains gene rearrangement (IgH-R) were admixed to the PTCL cells. ii. The second form mimicked diffuse large B-cell lymphoma as homogenous sheets, largely demarcated from the PTCL, of mononuclear, immature B-cell of CD20+, CD30+, CD45+, LMP1+, EBNA-2+ phenotype but with lack of monoclonal IgH-R were present. iii. In the third form scattered Hodgkin-Reed-Sternberg (HRS) type of cells were noticed which exhibited the CD15+/−, CD20−/+, CD30+, CD45−, LMP1+, EBNA-2- phenotype and in 50% showed clonal IgH gene rearrangement in whole tissue DNA extract. The IgH associated transcription factors’ (OCT2, BOB.1/OBF.1, PU.1) expression patterns in these cells corresponded to those of HRS cells in cHL. Based on analysis of 65 PTCLs, we have identified in the positive cases a highly significant increase of EBV+ small, reactive, resting B-cell compartment (75.9 / 100 HPF in PTCL vs. 1.5 / 100 HPF in control lymph nodes) likely to be due to the decreased immune surveillance. This progressive accumulation of EBV+ bystander B-cell population in PTCLs might be the source of various B-cell proliferations, which in any form represent major diagnostic pitfalls and require a careful differential diagnostic procedure.
C1 [Smuk, Gabor] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
[Keresztes, Katalin] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
[Kereskai, Laszlo] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
[Marton, Balazs] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
[Nagy, Zsofia] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
[Lacza, Agnes] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, 12 Szigeti Str, 7624 Pecs, Hungary.
RP Pajor, L (reprint author), University of Pecs, Department of Pathology, 7624 Pecs, Hungary.
EM laszlo.pajor@kk.pte.hu;titkar.pathology@kk.pte.hu
CR Barry ST, Jaffe SE, Sorbara L et al, 2003, Peripheral T-cell lymphomas expressing CD30 and CD15. Am J Surg Pathol 27:1513–1521
Quintanilla-Martinez L, Fend F, Rodriguez Moguel L et al, 1999, Peripheral T-cell lymphoma with Reed-Sternberg-like cell of Bcell phenotype and genotype associated with Epstein-Barr virus infection. Am J Surg Pathol 23:1233–1240
Pajor L, Kajtar B, Jakso P et al, 2006, Epstein-Barr virus-induced B-cell proliferation of Hodgkin’s and Reed-Sternberg cell phenoand genotype may develop in peripheral T-cell lymphomas. Histopathology 49:553–557
Ho WYJ, Ho CSF, Chan CLA et al, 1998, Frequent detection of Epstein-Barr virus-infected B cells in peripheral T-cell lymphomas. J Pathol 185:79–85
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Korbjuhn P, Anagnostopoulos I, Hummel M et al, 1993, Frequent latent Epstein-Barr virus infection of neoplastic T cells and Bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas. Blood 82:217–223
Suwiwat S, Pradutkanchana J, Ishida T et al, 2007, Quantitative analysis of cell-free Epstein-Barr virus DNA in the plasma of patients with peripheral T-cell and NK-cell lymphomas and peripheral T-cell proliferative diseases. J Clin Virol 40:277–283
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 377
EP 383
DI 10.1007/s12253-009-9233-2
PG 7
ER
PT J
AU Lu, HCh
Chou, FP
Yeh, KT
Chang, YS
Hsu, CN
Chang, JG
AF Lu, Hsiu-Chin
Chou, Fen-Pi
Yeh, Kun-Tu
Chang, Ya-Sian
Hsu, C Nicholas
Chang, Jan-Gowth
TI Expression of Protein Kinase C Family in Human Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Protein kinase C; Human hepatocellular carcinoma
ID Protein kinase C; Human hepatocellular carcinoma
AB Protein kinase Cs (PKCs) play important roles in signal transduction, cell regulation, and tumor formation. In the present study, we analyzed the expression of PKCs in human hepatocellular carcinoma (HCC) tissues and explored their roles in the development of HCC. Real-time quantitative PCR and immunohistochemistry showed that PKCβ and PKCθ were down-regulated in HCC tissues. Reduced expression of PKCθ is well correlated with the grade of cancer cells (p=0.009), and the down-regulated expression of PKCβII is associated with HBV infection (p=0.035). Our findings suggest particular roles of the two PKC isoenzymes in the hepatocarcinogenesis of human HCC.
C1 [Lu, Hsiu-Chin] Kaohsiung Medical University, College of Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Department of Laboratory MedicineKaohsiung, Taiwan, Republic of China.
[Chou, Fen-Pi] Chung Shan Medical University, Department of Medical Laboratory and BiotechnologyTaichung, Taiwan, Republic of China.
[Yeh, Kun-Tu] Changhua Christian Hospital, Department of PathologyChanghua, Taiwan, Republic of China.
[Chang, Ya-Sian] Kaohsiung Medical University, College of Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Department of Laboratory MedicineKaohsiung, Taiwan, Republic of China.
[Hsu, C Nicholas] Kaohsiung Medical University, College of Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Department of Laboratory MedicineKaohsiung, Taiwan, Republic of China.
[Chang, Jan-Gowth] Kaohsiung Medical University, College of Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Department of Laboratory MedicineKaohsiung, Taiwan, Republic of China.
RP Chang, JG (reprint author), Kaohsiung Medical University, College of Medicine, Kaohsiung Medical University Hospital, Institute of Clinical Research, Department of Laboratory Medicine, Kaohsiung, Taiwan, Republic of China.
EM jgchang@ms.kmuh.org.tw
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 385
EP 391
DI 10.1007/s12253-009-9228-z
PG 7
ER
PT J
AU Vuletic, A
Konjevic, G
Milanovic, D
Ruzdijic, S
Jurisic, V
AF Vuletic, Ana
Konjevic, Gordana
Milanovic, Desanka
Ruzdijic, Sabera
Jurisic, Vladimir
TI Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cell cycle; Promyelocytic leukemia; Proliferation; Retinoic acid; Differentiation
ID Cell cycle; Promyelocytic leukemia; Proliferation; Retinoic acid; Differentiation
AB Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). In this study we demonstrate that 13-cis-RA has a dose and time-dependant antiproliferative effect on HL-60 PML cell line, that it induces cell accumulation in resting G0/G1 phase of the cell cycle followed by an increase in CD11b granulocyte differentiation antigen expression. The obtained increase in the percentage of HL-60 cells in G0/G1 phase and complementary decrease in S phase of the cell cycle are accompanied by a decrease in the expression of cell cycle regulatory molecule cyclin B1. We also show the induction of interferon regulatory factor-1 (IRF-1) transcription that can, also, to some extent contribute to the antiproliferative effect of 13-cis-RA. Furthermore, down-regulation of Bcl-2 protein expression in 13-cis-RA treated HL-60 cells may contribute to sensitivity to apoptosis of growth arrested HL-60 promyelocytic cells.
C1 [Vuletic, Ana] Institute of Oncology and Radiology of SerbiaBelgrade, Serbia.
[Konjevic, Gordana] Institute of Oncology and Radiology of SerbiaBelgrade, Serbia.
[Milanovic, Desanka] University of Belgrade, Institute for Biological ResearchBelgrade, Serbia.
[Ruzdijic, Sabera] University of Belgrade, Institute for Biological ResearchBelgrade, Serbia.
[Jurisic, Vladimir] University of Kragujevac, Faculty of MedicineKragujevac, Serbia.
RP Vuletic, A (reprint author), Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
EM radovanovica@ncrc.ac.rs
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 393
EP 401
DI 10.1007/s12253-009-9241-2
PG 9
ER
PT J
AU Sun, Chm
Huang, Shf
Zeng, Jm
Liu, Db
Xiao, Q
Tian, Wj
Zhu, Xd
Huang, Zg
Feng, Wl
AF Sun, Cheng-ming
Huang, Shi-feng
Zeng, Jian-ming
Liu, Din-bing
Xiao, Qing
Tian, Wen-jun
Zhu, Xi-dan
Huang, Zong-gan
Feng, Wen-li
TI Per2 Inhibits K562 Leukemia Cell Growth In Vitro and In Vivo Through Cell Cycle Arrest and Apoptosis Induction
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circadian clock; Per2; Apoptosis; Cell cycle arrest; K562 cell
ID Circadian clock; Per2; Apoptosis; Cell cycle arrest; K562 cell
AB Per2 regulates other molecular and biochemical processes beyond their established role in the regulation of the mammalian circadian clock, herein we investigated the growth inhibiting potential of Per2 in human K562 leukemia cells and the underlying mechanisms .The results showed that over-expression of Per2 induced not only cell cycle arrest at G2/M phase but also an increase in apoptosis, which was confirmed by characteristic morphological changes, FCM and evident DNA fragmentation. Further experiments confirmed both up-regulation of P53 and down-regulation of CylinB1and C-myc. On the other hand, while P53 was found to be down-regulated. CylinB1 and C-myc were up-regulated. after Per2 knockdown. In leukemia mice, Per2 transfection was shown to suppress cellular proliferation and accelerate apoptosis of K562 cells. Moreover, fewer leukemia cells were found to have infiltrated into the livers and spleens of the mice from the Per2 transfected group as compared with those from the control group. In summary, Per2 displayed a significant anti-tumor effect through cell cycle arrest and apoptosis induction in K562 cells. These data further support the emerging role of the circadian clock in critical aspects of cancer development and thorough research is underway on the mechanism of Per2 in the leukemia.
C1 [Sun, Cheng-ming] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Huang, Shi-feng] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Zeng, Jian-ming] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Liu, Din-bing] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Xiao, Qing] Chongqing Medical University, Clinic College, Department of Hematology, 400016 Chongqing, China.
[Tian, Wen-jun] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Zhu, Xi-dan] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
[Huang, Zong-gan] Chongqing Medical University, Clinic College, Department of Hematology, 400016 Chongqing, China.
[Feng, Wen-li] Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
RP Feng, Wl (reprint author), Ministry of Education, Chongqing Medical University, Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, 400016 Chongqing, China.
EM fengwlcqmu@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 403
EP 411
DI 10.1007/s12253-009-9227-0
PG 9
ER
PT J
AU Zhong, F
Zhang, Sh
Shao, Ch
Yang, J
Wu, X
AF Zhong, Fei
Zhang, Shineng
Shao, Chunkui
Yang, Jing
Wu, Xiangyuan
TI Arsenic Trioxide Inhibits Cholangiocarcinoma Cell Growth and induces Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Arsenic trioxide; Apoptosis; Cholangiocarcinoma; Mitochondrial pathway; AKT
ID Arsenic trioxide; Apoptosis; Cholangiocarcinoma; Mitochondrial pathway; AKT
AB Arsenic trioxide (As2O3), an ingredient in many traditional Chinese medicines, has drawn broad attention due to its therapeutic effects on a variety of cancers, including some solid tumors. However, the effects of As2O3 on cholangiocarcinoma have not been reported. In the present study, we demonstrate for the first time that clinically obtainable concentrations of As2O3 inhibit cell growth and induce apoptosis in human cholangiocarcinoma SK-ChA-1 cells. As2O3-induced apoptosis was partially inhibited by caspase inhibitor and accompanied by changes in the expression of Bcl-2 family proteins, decrease of mitochondrial membrane potential (MMP), release of cytochrome C from mitochondria, activation of caspase-3, caspase-9, and cleavage of poly (ADP-ribose) polymerase (PARP). Thus As2O3 induces apoptosis in SK-ChA-1 cells via mitochondria-mediated, caspases-dependent pathways. As2O3 inhibition of Akt phosphorylation may contribute to As2O3-mediated cholangiocarcinoma cell growth inhibition and apoptosis induction.
C1 [Zhong, Fei] Sun Yat-Sen University, Third Affiliated Hospital, Department of Medical Oncology, 510630 Guangzhou, 510630, China.
[Zhang, Shineng] Sun Yat-Sen University, Second Affiliated Hospital, Department of GastroenterologyGuangzhou, 510120, China.
[Shao, Chunkui] Sun Yat-Sen University, Third Affiliated Hospital, Department of PathologyGuangzhou, 510630, China.
[Yang, Jing] Sun Yat-Sen University, Third Affiliated Hospital, VIP Health-care centerGuangzhou, 510630, China.
[Wu, Xiangyuan] Sun Yat-Sen University, Third Affiliated Hospital, Department of Medical Oncology, 510630 Guangzhou, 510630, China.
RP Wu, X (reprint author), Sun Yat-Sen University, Third Affiliated Hospital, Department of Medical Oncology, 510630 Guangzhou, China.
EM Wuxyonco@yahoo.com.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 413
EP 420
DI 10.1007/s12253-009-9234-1
PG 8
ER
PT J
AU Becsagh, P
Varga, K
Szakacs, O
Kopper, L
Orosz, Zs
AF Becsagh, Peter
Varga, Katalin
Szakacs, Orsolya
Kopper, Laszlo
Orosz, Zsolt
TI High Resolution Melting Curve Analysis of DNA Sequence Alterations of Various Sizes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melting curve; High resolution; DNA; Mutations; GIST
ID Melting curve; High resolution; DNA; Mutations; GIST
AB In the diagnostic workflow we need to think in algorithms, containing more assays. One of the most important task in the management of cancer patient is to detect nucleic acid sequence changes in clinical specimens. Before using the most expensive method to analyze direct our targets, a screening assay is needed to reduce the number of samples. In the detection of gene-sequence alterations classical screening methods are available, as SSCP, DGGE or TGGE, (Finke Exp Clin Endocrinol Diabetes 104:92–97, 1996; Lessa and Applebaum Mol Ecol 2:119–129, 1993) however these are very time consuming processes. At this time in the molecular lab the real-time PCR equipments are very popular and with the function of melting curve analysis it can be a very convenient, simple and cost-efficient screening method.
C1 [Becsagh, Peter] Roche Hungary LtdBudaors, Hungary.
[Varga, Katalin] National Institute of OncologyBudapest, Hungary.
[Szakacs, Orsolya] MMM LtdBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Orosz, Zsolt] National Institute of OncologyBudapest, Hungary.
RP Becsagh, P (reprint author), Roche Hungary Ltd, Budaors, Hungary.
EM peter.becsagh@roche.com
CR Finke R, 1996, Theoretical basis and application of molecular diagnostics. Exp Clin Endocrinol Diabetes 92(Suppl 4):92–97, Review
Lessa EP, Applebaum G, 1993, Screening techniques for detecting allelic variation in DNA sequences. Mol Ecol 2, 2):119–129, Review
Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, Pryor RJ, 2003, High resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem 49:853–860
Herrmann MG, Durtschi JD, Bromley LK,Wittwer CT, Voelkerding KV, 2006, DNA melting analysis for mutation scanning and genotyping: a cross platform comparison. Clin Chem 52:494–503
Seipp MT, Durtschi JD, Voelkerding KV, Wittwer CT, 2009, Multiplex amplicon genotyping by high-resolution melting. J Biomol Tech 20:160–164
Wittwer CT, 2009, High-resolution DNA melting analysis: advancements and limitations. Hum Mutat 30:857–859
Crews N, Wittwer CT, Montgomery J et al, 2009, Spatial DNA melting analysis for genotyping and variant scanning. Anal Chem 81:2053–2058
Willmore-Payne C, Holden JA, Wittwer CT, Layfield LJ, 2009, The use of EGFR exon 19 and 21 unlabeled DNA probes to screen for activating mutations in non-small cell lung cancer. J Biomol Tech 19:217–224
Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, Besmer P, 2003, Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 9(9):3329–3337
Talaulikar D, Gray JX, Shadbolt B, McNiven M, Dahlstrom JE, 2008, A comparative study of the quality of DNA obtained from fresh frozen and formalin-fixed decalcified paraffin-embedded bone marrow trephine biopsy specimens using two different methods. J Clin Pathol 61(1):119–123, Epub 2007 Jun
Erali M, Voelkerding KV, Wittwer CT, 2008, High resolution melting applications for clinical laboratory medicine. Exp Mol Pathol 85:50–58
Erali M, Wittwer CT, 2010, High resolution melting analysis for gene scanning. Methods, article in press., DOI 10.1016/j. ymeth.2010.01.013
Korbie DJ, Mattick JS, 2008, Touchdown PCR for increased specificity and sensitivity in PCR amplification. Nat Protoc 3, 9):1452–1456
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 421
EP 426
DI 10.1007/s12253-010-9274-6
PG 6
ER
PT J
AU Adly, AM
Hussein, RAM
AF Adly, A Mohamed
Hussein, Rezk Abdelwahed Mahmoud
TI Immunohistological Profile of the Ras Homologous B Protein (RhoB) in Human Testes Showing Normal Spermatogenesis, Spermatogenic Arrest and Sertoli Cell Only Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RhoB; Human testis; Fertility; Infertility; Ras
ID RhoB; Human testis; Fertility; Infertility; Ras
AB Ras homologous B protein (RhoB) belongs to the Ras homologous subfamily which consists of low molecular weight (21 kDa) GTP-binding proteins. Rho proteins are regulatory molecules associated with various kinases and as such they mediate changes in cell shape, contractility, motility and gene expression. To date, no data are available about the expression pattern of RhoB protein in the human testis showing normal and abnormal spermatogenesis. The present study addresses these issues. Human testicular biopsy specimens were obtained from patients suffering from post-testicular infertility (testis showing normal spermatogenesis, 10 cases) and testicular infertility (testis showing Sertoli cell only syndrome and spermatogenic arrest, 10 patients each). The expression of RhoB was examined using in situ immunofluorescent staining methods. In testes showing normal spermatogenesis, RhoB had a strong expression in the seminiferous epithelium (cytoplasm of Sertoli-cells, spermatogonia and spermatocytes) and in the interstitium (Leydig cells). RhoB expression was weak in the myofibroblasts and absent in the spermatids and sperms. In the testes showing abnormal spermatogenesis, RhoB expression wasmoderate in the seminiferous epithelium (cytoplasm of Sertoli cells, spermatogonia and spermatocytes) and was completely absent in the Leydig cells, myofibroblasts, spermatids and sperms. To the best of our knowledge, this study provides the first morphological indication that RhoB protein is expressed in human testis and its expression undergoes testicular infertility associated changes. These findings suggest the involvement of RhoB in the process of spermatogenesis in human and their possible therapeutic ramifications in testicular infertility are open for further investigations.
C1 [Adly, A Mohamed] Sohag University, Faculty of Science, Department of ZoologySohag, Egypt.
[Hussein, Rezk Abdelwahed Mahmoud] King Khalid University, Assir Central Hospital, Department of PathologyAbha, Saudi Arabia.
RP Hussein, RAM (reprint author), King Khalid University, Assir Central Hospital, Department of Pathology, Abha, Saudi Arabia.
EM mrcpath17@gmail.com;mrh17@gawab.com
CR Hu E, 2006, Recent patents on Rho signaling pathway as therapeutic target for cardiovascular diseases. Recent Patents Cardiovasc Drug Discov 1:249–263
Berken A, Wittinghofer A, 2008, Structure and function of Rhotype molecular switches in plants. Plant Physiol Biochem 46:380– 393
Nowak JM, Grzanka A, Zuryn A, Stepien A, 2008, The Rho protein family and its role in the cellular cytoskeleton. Postepy Hig Med Dosw, Online, 62:110–117
Modarressi MH, Cheng M, Tarnasky HA, Lamarche-Vane N, de Rooij DG, Ruan Y, van der Hoorn FA, 2004, A novel testicular RhoGAP-domain protein induces apoptosis. Biol Reprod 71:1980–1990
Genth H, Dreger SC, Huelsenbeck J, Just I, 2008, Clostridium difficile toxins: more than mere inhibitors of Rho proteins. Int J Biochem Cell Biol 40:592–597
Nakakuki T, Ito M, Iwasaki H, Kureishi Y, Okamoto R, Moriki N, Kongo M, Kato S, Yamada N, Isaka N, Nakano T, 2005, Rho/ Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator inhibitor-1 expression in endothelial cells. Arterioscler Thromb Vasc Biol 25:2088–2093
Sequeira L, Dubyk CW, Riesenberger TA, Cooper CR, van Golen KL, 2008, Rho GTPases in PC-3 prostate cancer cell morphology, invasion and tumor cell diapedesis. Clin Exp Metastasis 25:569– 579
Zhao L, Wang H, Li J, Liu Y, Ding Y, 2008, Overexpression of Rho GDP-dissociation inhibitor Alpha is associated with tumor progression and poor prognosis of colorectal cancer. J Proteome Res 7(9):3994–4003
Scott RW, Olson MF, 2007, LIM kinases: function, regulation and association with human disease. J Mol Med 85:555–568
Ramos S, Khademi F, Somesh BP, Rivero F, 2002, Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse. Gene 298:147–157
Liu GY, Gao SZ, Ge CR, Zhang X, 2008, Cloning, nucleotide sequence and tissue expression profile of three novel porcine genes—RHOB, RHOG and PRAF1. Mol Biol, Mosk, 42:59– 62
Kao TJ, Millette CF, 2007, L-type voltage-operated Ca(+2, channels modulate transient Ca(+2, influx triggered by activation of Sertoli cell surface L-selectin. J Cell Biochem 101:1023–1037
Lui WY, Lee WM, Cheng CY, 2003, Sertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathway. Biol Reprod 68:2189–2206
Lui WY, Lee WM, Cheng CY, 2003, Rho GTPases and spermatogenesis. Biochim Biophys Acta 1593:121–129
Lui WY, Mruk DD, Cheng CY, 2005, Interactions among IQGAP1, Cdc42, and the cadherin/catenin protein complex regulate Sertoli-germ cell adherens junction dynamics in the testis. J Cell Physiol 202:49–66
Shim H, Lee H, Jeoung D, 2006, Cancer/testis antigen cancerassociated gene, CAGE, promotes motility of cancer cells through activation of focal adhesion kinase, FAK). Biotechnol Lett 28:2057–2063
Kamai T, Arai K, Tsujii T, Honda M, Yoshida K, 2001, Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour. BJU Int 87:227–231
Hussein MR, Abou-Deif ES, Bedaiwy MA, Said TM, Mustafa MG, Nada E, Ezat A, Agarwal A, 2005, Phenotypic characterization of the immune and mast cell infiltrates in the human testis shows normal and abnormal spermatogenesis. Fertil Steril 83:1447–1453
Hussein MR, Abu-Dief EE, Abou El-Ghait AT, Adly MA, Abdelraheem MH, 2006, Melatonin and roentgen irradiation of the testis. Fertil Steril 86:750–752
Hussein MR, Abu-Dief EE, Abou El-Ghait AT, Adly MA, Abdelraheem MH, 2006, Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats: an animal model. Int J Exp Pathol 87:237–250
Hirano K, Matsuura F, Tsukamoto K, Zhang Z, Matsuyama A, Takaishi K, Komuro R, Suehiro T, Yamashita S, Takai Y, Matsuzawa Y, 2000, Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease—the small G protein may play a role in cholesterol efflux. FEBS Lett 484:275–279
Freeman EA, Jani P, Millette CE, 2002, Expression and potential function of Rho family small G proteins in cells of the mammalian seminiferous epithelium. Cell Commun Adhes 9:189–204
Nakamura K, Fujita A, Murata T, Watanabe G, Mori C, Fujita J, Watanabe N, Ishizaki T, Yoshida O, Narumiya S, 1999, Rhophilin, a small GTPase Rho-binding protein, is abundantly expressed in the mouse testis and localized in the principal piece of the sperm tail. FEBS Lett 445:9–13
Takahashi H, Koshimizu U, Miyazaki J, Nakamura T, 2002, Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene. Dev Biol 241:259–272
Cunto FD, Imarisio S, Camera P, Boitani C, Altruda F, Silengo L, 2002, Essential role of citron kinase in cytokinesis of spermatogenic precursors. J Cell Sci 115:4819–4826
Togawa A, Miyoshi J, Ishizaki H, Tanaka M, Takakura A, Nishioka H, Yoshida H, Doi T, Mizoguchi A, Matsuura N, Niho Y, Nishimune Y, Nishikawa S, Takai Y, 1999, Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Oncogene 18:5373–5380
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 427
EP 433
DI 10.1007/s12253-009-9232-3
PG 7
ER
PT J
AU Kadota, K
Kushida, Y
Miyai, Y
Katsuki, N
Hayashi, T
Bando, K
Shibuya, Sh
Haba, R
AF Kadota, Kyuichi
Kushida, Yoshio
Miyai, Yumi
Katsuki, Naomi
Hayashi, Toshitetsu
Bando, Kenji
Shibuya, Shinsuke
Haba, Reiji
TI Epidermoid Cyst in an Intrapancreatic Accessory Spleen: Three Case Reports and Review of the Literatures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epidermoid cyst; Pancreas; Accessory spleen; Carbohydrate antigen 19-9; Immunohistochemistry; Histogenesis
ID Epidermoid cyst; Pancreas; Accessory spleen; Carbohydrate antigen 19-9; Immunohistochemistry; Histogenesis
AB The development of an epidermoid cyst in an intrapancreatic accessory spleen is an extremely rare lesion, with only 17 cases being reported in the English literature. All such cases were located in the pancreatic tail, some of which showed carbohydrate antigen 19-9 (CA19-9) immunoreactivity in the lining of the epithelium. A few of themindicated an elevation of the serum CA19-9 level. Here we report three cases of an epidermoid cyst in an intrapancreatic accessory spleen. Cases 1 and 2 were 57-year-old and 70-year-old women, while case 3 was a 37-year-old man. All three cases were asymptomatic. Serum CA19-9 levels showed within normal limits (case 1), slightly elevated (case 2), and clearly elevated (case 3). They underwent a distal pancreatectomy with splenectomy (cases 1 and 2) and without splenectomy (case 3). Grossly, the surgical specimen was a welldemarcated, multiple (case 1) or solitary (cases 2 and 3) cystic mass in the pancreatic tail. A high level of fluid CA 19-9 was detected in case 1. Microscopically, the cystic walls were lined with squamous and cuboidal epithelium, which were surrounded by normal splenic tissue and hyalinized fibrous tissue. The lining squamous epithelium was revealed as nonkeratinizing (Cases 1and 2) or keratinizing (Case 3). Immunohistochemically, CA19-9 was positive in the monolayer and surface layer of the cuboidal epithelium, but negative for the keratinizing squamous epithelium. As for the histogenesis, it is suggested that the cystic lining of the epithelium may derive from the pancreatic duct which protrudes into the accessory spleen.
C1 [Kadota, Kyuichi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Kushida, Yoshio] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Miyai, Yumi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Katsuki, Naomi] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Hayashi, Toshitetsu] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Bando, Kenji] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Shibuya, Shinsuke] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
[Haba, Reiji] Kagawa University, University Hospital, Department of Diagnostic Pathology, 1750-1, Ikenobe, Miki-cho, 761-0793 Kagawa, Japan.
RP Kadota, K (reprint author), Kagawa University, University Hospital, Department of Diagnostic Pathology, 761-0793 Kagawa, Japan.
EM qichi@med.kagawa-u.ac.jp
CR Davidson ED, Campbell WG, Hersh T, 1980, Epidermoid splenic cyst occurring in an intrapancreatic accessory spleen. Dig Dis Sci 25:964–967
Morohoshi T, Hamamoto T, Kunimura T et al, 1991, Epidermoid cyst derived from an accessory spleen in the pancreas. A case report with literature survey. Acta Pathol Jpn 41:916–921
Nakae Y, Hayakawa T, Kondo T et al, 1991, Epidermoid cyst occurring in a pancreatic accessory spleen. J Clin Gastroenterol 13:362–364
Tang X, Tanaka Y, Tsutsumi Y, 1994, Epithelial inclusion cysts in an intrapancreatic accessory spleen. Pathol Int 44:652–654
Furukawa H, Kosuge T, Kanai Y, Mukai K, 1998, Epidermoid cyst in an intrapancreatic accessory spleen: CT and pathologic findings. AJR Am J Roentgenol 171:271
Higaki K, Jimi A, Watanabe J et al, 1998, Epidermoid cyst of the spleen with CA19, 9 or carcinoembryonic antigen productions: report of three cases. Am J Surg Pathol 22:704–708
Tateyama H, Tada T, Murase T et al, 1998, Lymphoepithelial cyst and epidermoid cyst of the accessory spleen in the pancreas. Mod Pathol 11:1171–1177
Sasou S, Nakamura S, Inomata M, 1999, Epithelial splenic cysts in an intrapancreatic accessory spleen and spleen. Pathol Int 49:1078–1083
Choi SK, Ahn SI, Hong KC et al, 2000, A case of epidermoid cyst of the intrapancreatic accessory spleen. J Korean Med Sci 15:589–592
Tsutsumi S, Kojima T, Fukai Y et al, 2000, Epidermoid cyst of an intrapancreatic accessory spleen, a case report. Hepatogastroenterology 47:1462–1464
Horibe Y, Murakami M, Yamao K et al, 2001, Epithelial inclusion cyst, epidermoid cyst, formation with epithelioid cell granuloma in an intrapancreatic accessory spleen. Pathol Int 51:50–54
Sonomura T, Kataoka S, Chikugo T et al, 2002, Epidermoid cyst originating from an intrapancreatic accessory spleen. Abdom Imaging 27:560–562
Kanazawa H, Kamiya J, Nagino M et al, 2004, Epidermoid cyst in an intrapancreatic accessory spleen: a case report. J Hepatobiliary Pancreat Surg 11:61–63
Ru K, Kalra A, Ucci A, 2007, Epidermoid cyst of intrapancreatic accessory spleen. Dig Dis Sci 52:1229–1232
Itano O, Shiraga N, Kouta E et al, 2008, Epidermoid cyst originating from an intrapancreatic accessory spleen. J Hepatobiliary Pancreat Surg 15:436–439
Servais EL, Sarkaria IS, Solomon GJ et al, 2008, Giant epidermoid cyst within an intrapancreatic accessory spleen mimicking a cystic neoplasm of the pancreas: case report and review of the literature. Pancreas 36:98–100
Gleeson FC, Kendrick ML, Chari ST et al, 2008, Epidermoid accessory splenic cyst masquerading as a pancreatic mucinous cystic neoplasm. Endoscopy 40:E141–2
Robbins FG, Yellin AE, Lingua RW et al, 1978, Splenic epidermoid cysts. Ann Surg 187:231–235
Halpert B, Alden ZA, 1964, Accessory spleens in or at the tail of the pancreas. A survey of 2, 700 additional necropsies. Arch Pathol 77:652–654
Burrig KF, 1988, Epithelial, true, splenic cysts. Pathogenesis of the mesothelial and so-called epidermoid cyst of the spleen. Am J Surg Pathol 12:275–81
Elit L, Aylward B, 1989, Splenic cyst carcinoma presenting in pregnancy. Am J Hematol 32:57–60
Schacht V, Dadras SS, Johnson LA et al, 2005, Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumours. Am J Pathol 166:913–921
Ough YD, Nash HR, Wood DA, 1981, Mesothelial cysts of the spleen with squamous metaplasia. Am J Clin Pathol 76:666–669
Lifschitz-Mercer B, Open M, Kushnir I, Czernobilsky B, 1994, Epidermoid cyst of the spleen: a cytokeratin profile with comparison to other squamous epithelia. Virchows Arch 424:213–216
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 435
EP 442
DI 10.1007/s12253-009-9229-y
PG 8
ER
PT J
AU Svec, A
Bury, Y
AF Svec, Alexandr
Bury, Yvonne
TI Haemangioma of the Parathyroid Gland. Does it Really Exist?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Parathyroid gland; Chromogranin A; Haemangioma; VEGF; Tumour-associated vascular proliferations
ID Parathyroid gland; Chromogranin A; Haemangioma; VEGF; Tumour-associated vascular proliferations
AB We are reporting a case of a capillary haemangiomalike proliferation arising within a parathyroid gland adenoma, associated with primary hyperparathyroidism. The vessel proliferation bearing a close resemblance to a capillary haemangioma consisted of tightly packed capillaries, endothelial buds and occasional small caliber muscle-containing vessels. The observation expands the spectrum of tumourassociated vascular proliferations by adding an exuberant haemangioma-like pattern to its extreme end. These are a heterogeneous group of lesions reportedly induced by aberrant production of angiogenic factors. We investigated expression of VEGF, pKDR, FGF2, HIF1α and HIF2α and only VEGF gave a strong positive reaction in the adenoma cells entrapped in the vascular meshwork. Although this does not constitute a proof that aberrant VEGF production was a causative agent, unexpected supportive evidence for its pathogenic role emerged from a failure to detect chromogranin A. Chromogranin A is a precursor of several regulatory proteins, including vasostatin I, a multilevel suppressor of VEGF. The production of vasostatin I may have been reduced in a chromogranin A-negative adenoma which could lead to a loss of its opposing effect on VEGF–regulated processes. The only two other published cases of haemangioma of the parathyroid gland were reported in patients diagnosed with primary parathyroid hyperplasia with hyperparathyroidism, a pathophysiologic condition similar to our case. Therefore we raise the question whether these tumours could also represent a reactive phenomenon.
C1 [Svec, Alexandr] James Cook University Hospital, Department of Cellular Pathology, Marton Road, TS4 3BW Middlesbrough, UK.
[Bury, Yvonne] James Cook University Hospital, Department of Cellular Pathology, Marton Road, TS4 3BW Middlesbrough, UK.
RP Svec, A (reprint author), James Cook University Hospital, Department of Cellular Pathology, TS4 3BW Middlesbrough, UK.
EM alexandr.svec@vfn.cz
CR Chan JKC, 2007, Tumours of the thyroid and parathyroid glands. Parathyroid glands. In: Fletcher CDM, ed, Diagnostic histopathology of tumours, 3rd edn. Churchill Livingstone, London
Rosai J, 2004, Parathyroid glands. In: Rosai J, ed, Rosai and Ackerman's surgical pathology, 9th edn. Mosby, St Louis
DeLellis RA, Williams ED, 2004, Tumours of the thyroid and parathyroid. In: DeLellis RA, Lloyd RV, Heitz PU, Eng Ch, eds, Pathology and genetics of tumours of endocrine organs. IARC, Lyon
Garcia de la Torre N, Buley I, Wass JAH et al, 2004, Angiogenesis and lymphangiogenesis in parathyroid proliferative lesions. J Clin Endocrinol Metab 89:2890–2896
Merino M, Chuaqui R, Fernandez P, 1996, Parathyroid haemangioma: a report of two cases. Endocr Pathol 7:319–322
Gaudin P, Rosai J, 1995, Florid vascular proliferation associated with neural and neuroendocrine neoplasms. A diagnostic clue and potential pitfall. Am J Surg Pathol 19:642–652
Baloch ZW, LiVolsi VA, 1998, Intravascular Kaposi's-like spindle cell proliferation of the capsular vessels of follicular-derived thyroid carcinomas. Mod Pathol 11:995–998
Tse LL, Chan I, Chan JK, 2001, Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma. Histopathology 39:463–468
Vodovnik A, 2002, Capsular vascular proliferation associated with thyroid paraganglioma. Histopathology 41:273
Kuhn E, De Anda J, Manoni S et al, 2006, Renal cell carcinoma associated with prominent angioleiomyoma-like proliferation: report of 5 cases and review of the literature. Am J Surg Pathol 30:1372–1381
Carter W, Uy K, Ward M et al, 2000, Parathyroid-induced angiogenesis is VEGF-dependent. Surgery 128:458–464
Lazaris AC, Tseleni-Balafouta S, Papathomas T et al, 2006, Immunohistochemical investigation of angiogenic factors in parathyroid proliferative lesions. Eur J Endocrinol 154:827–833
Martins P, Schmitt F, Almeida H et al, 2008, Evaluation of parathyroid gland angiogenesis in chronic kidney disease associated with secondary hyperparathyroidism. Nephrol Dial Transplant 23:2889–2894
Rashid G, Bernheim J, Green J et al, 2008, Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor. Eur J Clin Invest 38:798–803
Viacava P, Bocci G, Fanelli G et al, 2006, Microvessel density in human normal and neoplastic parathyroids. Endocr Pathol 17:175–181
Belloni D, Scabini S, Foglieni C et al, 2007, The vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration. FASEB J 21:3052–62
Gould VE, Wiedenmann B, Lee I et al, 1987, Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol 126:243–57
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 443
EP 446
DI 10.1007/s12253-009-9236-z
PG 4
ER
PT J
AU Matsuda, I
Imai, Y
Hirota, S
AF Matsuda, Ikuo
Imai, Yukihiro
Hirota, Seiichi
TI Global Histone Modification Profiles are Well Conserved Between Normal B Lymphocytes and Neoplastic Counterparts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diagnostic histopathology; Tumor; Cell type; Global histone modification; Immunohistochemistry; Reactive lymphoid hyperplasia; Germinal center B cell; Mantle zone B cells; Follicular lymphoma; Mantle cell lymphoma
ID Diagnostic histopathology; Tumor; Cell type; Global histone modification; Immunohistochemistry; Reactive lymphoid hyperplasia; Germinal center B cell; Mantle zone B cells; Follicular lymphoma; Mantle cell lymphoma
AB The identification of cell type is essential in diagnostic tumor histopathology. We hypothesized that some patterns of global histone modification are specific to both particular cell types of non-neoplastic tissues and their neoplastic counterparts. To examine the hypothesis in lymphoid cells, global histone modification patterns of germinal center and mantle zone B cells in reactive lymphoid hyperplasia (RLH) were compared with those of follicular lymphoma (FL) and mantle cell lymphoma (MTL) cells by immunohistochemistry. We revealed that FL cells and MTL cells exhibited the similar histone modification pattern to that of germinal center B lymphocytes and mantle zone B lymphocytes in RLH, respectively. These results indicate that global histone modification profiles specific to non-neoplastic germinal center B lymphocytes and mantle zone B lymphocytes are well conserved in corresponding neoplastic lymphoma cells, and suggest that they will be indicative of tumor cell type at least in B cell lymphoma.
C1 [Matsuda, Ikuo] Hyogo College of Medicine, Department of Surgical Pathology, 1-1 Mukogawa-cho, 663-8501 Nishinomiya, Hyogo, Japan.
[Imai, Yukihiro] Kobe City Medical Center General Hospital, Department of PathologyKobe, Hyogo, Japan.
[Hirota, Seiichi] Hyogo College of Medicine, Department of Surgical Pathology, 1-1 Mukogawa-cho, 663-8501 Nishinomiya, Hyogo, Japan.
RP Hirota, S (reprint author), Hyogo College of Medicine, Department of Surgical Pathology, 663-8501 Nishinomiya, Japan.
EM hiros@hyo-med.ac.jp
CR Jones PA, Baylin SB, 2007, The epigenetics of cancer. Cell 128:683–692
Swerdlow SH, Campo E, Harris NL et al, eds,, 2008, WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO, Geneva
Seligson DB, Horvath S, Shi T et al, 2005, Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435:1262–1266
Barlesi F, Giaccone G, Gallegos-Ruiz MI et al, 2007, Global histone modifications predict prognosis of resected non-small-cell lung cancer. J Clin Oncol 25:4358–4364
Tzao C, Tung HJ, Jin JS et al, 2009, Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus. Mod Pathol 22:252–260
Krivtsov AV, Armstrong SA, 2007, MLL translocations, histone modifications and leukemia stem-cell development. Nat Rev Cancer 7:823–833
Pal S, Balocchi RA, Byrd JC et al, 2007, Low levels of miR-92b/ 96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J 26:3558–3569
Seligson DB, Horvath S, McBrian MA et al, 2009, Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 174:1619–1628
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 447
EP 451
DI 10.1007/s12253-009-9224-3
PG 5
ER
PT J
AU Bardi, E
Dobos,
Kappelmayer, J
Kiss, Cs
AF Bardi, Edit
Dobos, Eva
Kappelmayer, Janos
Kiss, Csongor
TI Differential Effect of Corticosteroids on Serum Cystatin C in Thrombocytopenic Purpura and Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute lymphoblastic leukemia; Coricosteroid therapy; Cystatin C; Glomerular function; Idiopathic thrombocytopenic purpura; Leukemic cell burden
ID Acute lymphoblastic leukemia; Coricosteroid therapy; Cystatin C; Glomerular function; Idiopathic thrombocytopenic purpura; Leukemic cell burden
AB The aim of our study was to evaluate the influence of steroid therapy on serum cystatin C (cysC) concentrations in patients with acute lymphoblastic leukemia (ALL) and idiopthias thrombocytopenias purpura (ITP). We studied 17 patients with ITP (girls: boys=5:12, mean age: 7.6 yrs, range between 1 to 17 years) and 18 patients with ALL (girls: boys=6:12, mean age: 6.3 yrs, range between 2 to 17 years). CysC and white blood cell count (WBC) in both group of patients were determined before and after 300 mg/m2 cumulative dose of steroid therapy. Corticosteroids increased the level of cysC in both groups of patients, however significant increase was found only in ITP patients between pre- and posttreatment values (0,96±0,27 mg/L vs. 1,16±0,3 mg/L, p=0,02). Pretreatment cysC concentrations were within the reference range in patients with ITP but not with ALL and were significantly higher in ALL patients, than in ITP patients (1,23±1,12 mg/L vs. 0,96±0,27 mg/L, p=0,02). Pretreatment WBC of ALL patients were significantly higher than of ITP patients (22,58 G/L, min. 3,5 G/L, max. 102,1 G/L vs. 7,46 G/L, min. 4,8 G/L, max. 12,3 G/L, p=0.03). We have found significant correlation between pretreatment cysC and WBC values in ALL patients (p=0.04). Although the concentration of cysC may be slightly and reversibly influenced by corticosteroid treatment, cysC is sensitive to detect early and moderate deteoriantation of GFR in children with cancer.
C1 [Bardi, Edit] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, 98 Nagyerdei Circle, 4032 Debrecen, Hungary.
[Dobos, Eva] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, 98 Nagyerdei Circle, 4032 Debrecen, Hungary.
[Kappelmayer, Janos] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, 98 Nagyerdei Circle, 4032 Debrecen, Hungary.
RP Bardi, E (reprint author), University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, 4032 Debrecen, Hungary.
EM editbardi@hotmail.com
CR Bardi E, Bobok I, Olah VA, Olah E, Kappelmayer J, Kiss C, 2004, Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatr Nephrol 10:1145–1147
Mussap M, Plebani M, 2004, Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci 41:467–550
Risch L, Herklotz R, Blumberg A, Huber AR, 2001, Effects of glucocorticoid immunosuppression on serum cystatin c concentrations in renal transplant patients. Clin Chem 47:2055–2059
Demirtas S, Akan O, Can M, Elmali E, Akan H, 2006, Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin Biochem 39:115–118
Cimerman N, Brguljan PM, Krasovec M, 2000, Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta 300:83–95
Bokenkamp A, van Wijk JAE, Lentze MJ, 2002, Effect of corticosteroid therapy on serum cystatin C and ß2-microglobulin concentrations. Clin Chem 48:1123–1126
Schrappe M, Reiter A, Zimmermann M et al, 2000, Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995, Berlin-Frankfurt- Munster. Leukemia 14:2205–2222
Jaffe M, 1986, On the precipitation that picric acid produces in normal urine, and on a new reaction of creatinine [in German]. Zietschrift Phisologica Chemica 10:391–400
Counahan R, Chantler C, Ghazali S, Kirkwood B, Rose F, Barrat TM, 1976, Estimation of glomerular filtration rate from plasma creatinine concentration in children. Arch Dis Child 51:875–878
Bardi E, Olah VA, Bartyik K, Endreffy E, Jenei C, Kappelmayer J, Kiss C, 2004, Late effects on renal glomerular and tubular function of childhood cancer survivors. Pediatr Blood Cancer 43:668–673
Bjarnadottir M, Grubb A, Olafsson I, 1995, Promoter mediated dexamethasone-induced increase in cystatin C production in HeLa cels. Scand J Clin Lab Invest 55:617–623
Fricker M, Wiesli P, Brandle M, Schwegler B, Schmid C, 2003, Impact of thyroid dysfunction on serum cystatin c. Kidney Int 63:1944–1947
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 453
EP 456
DI 10.1007/s12253-009-9243-0
PG 4
ER
PT J
AU Bonavina, L
Laface, L
Picozzi, S
Nencioni, M
Siboni, S
Bona, D
Sironi, A
Sorba, F
Clemente, C
AF Bonavina, Luigi
Laface, Letizia
Picozzi, Stefano
Nencioni, Marco
Siboni, Stefano
Bona, Davide
Sironi, Andrea
Sorba, Francesca
Clemente, Claudio
TI Proposal of a Punch Biopsy Protocol as a Pre-requisite for the Establishment of a Tissue Bank from Resected Esophageal Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal carcinoma; Punch biopsy; Tumor bank; Tissue bank; Surgical oncology
ID Esophageal carcinoma; Punch biopsy; Tumor bank; Tissue bank; Surgical oncology
AB With the development of tissue banking, a need for homogeneous methods of collection, processing, and storage of tissue has emerged. We describe the implementation of a biological bank in a high-volume, tertiary care University referral center for esophageal cancer surgery.We also propose an original punch biopsy technique of the surgical specimen. The method proved to be simple, reproducible, and not expensive. Unified standards for specimen collection are necessary to improve results of specimen-based diagnostic testing and research in surgical oncology.
C1 [Bonavina, Luigi] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Laface, Letizia] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Picozzi, Stefano] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Nencioni, Marco] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Siboni, Stefano] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Bona, Davide] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Sironi, Andrea] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Sorba, Francesca] University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical SciencesMilan, Italy.
[Clemente, Claudio] Istituto Clinico S. Ambrogio, Division of PathologyMilan, Italy.
RP Bonavina, L (reprint author), University of Milano Medical School, Division of General Surgery, IRCCS Policlinico San Donato, Department of Medical and Surgical Sciences, Milan, Italy.
EM luigi.bonavina@unimi.it
CR Howe M, 2001, National prostate tumour bank launched in Australia. Lancet Oncol 2:656
Morrin H, Gunningham S, Currie M, Dachs G, Fox S, Robinson B, 2005, The Christchurch tissue bank to support cancer research. NZMJ 118:1–12
Teodorovic I, Therrasse P, Spatz A et al, 2003, Human tissue research: EORTC recommendations on its practical consequences. Eur J Cancer 39:2256–63
Leyland-Jones B, Ambrosone C, Bartlett J, Ellis M, Enos R, Raji A et al, 2008, Recommendations for collection and handling of specimens from group breast cancer clinical trials. J Clin Oncol 26:5638–44
Siewert R, Lordick F, Ott K, Stein H, Weber W, Becker K et al, 2007, Induction therapy in Barrett cancer. Influence on surgical risk and outcome. Ann Surg 246:624–631
Pennathur A, Luketich J, 2008, Resection for esophageal cancer: strategies for optimal management. Ann Thorac Surg 85:S751–756
Kandioler D, Hejna M, Zwrtek R et al, 2007, p53 adapted neoadjuvant therapy for esophageal cancer: pilot study. J Clin Oncol 25:201s, abstract 4535)
Ota Y, Tagagi Y, Osaka Y, Shinohara M, Hoshino S, Tsuchida A et al, 2007, Usefulness of serum protein profiling for prediction of preoperative chemoradiosensitivity of esophageal cancer. Oncol Rep 18:653–657
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 457
EP 460
DI 10.1007/s12253-009-9244-z
PG 4
ER
PT J
AU Perez, OL
Barbisan, G
Ottino, A
Pianzola, H
Golijow, DC
AF Perez, Orlando Luis
Barbisan, Gisela
Ottino, Anabel
Pianzola, Horacio
Golijow, Daniel Carlos
TI Human Papillomavirus DNA and Oncogene Alterations in Colorectal Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human Papillomavirus; Colorectal carcinoma; Viral integration; Proto-oncogene activation; k-ras; c-myc
ID Human Papillomavirus; Colorectal carcinoma; Viral integration; Proto-oncogene activation; k-ras; c-myc
AB The aim of the present study is to determine the presence and molecular integrity of high-risk HPV types in colorectal adenocarcinomas and to assess whether viral DNA is related to common proto-oncogene alterations, such as k-ras mutations and c-myc gene amplification, in colorectal cancer. Seventy-five colorectal adenocarcinomas were screened for HPV infection using nested-PCR (MY09/11-GP5+/6+). HPV typing was performed by type-specific PCR for HPV 16 and HPV 18 DNA. Unidentified samples were subsequently sequenced to determine the viral genotype. The physical status of HPV was determined by a nested PCR approach for type-specific E2 sequences. Cmyc amplification was assessed by co-amplification with β-globin as control locus, and mutation in k-ras codons 12 and 13 by ARMS-PCR. Overall, HPV was detected in thirty-three colorectal specimens (44%). HPV 16 was the prevalent type (16/75), followed by HPV 18 (15/75), HPV 31 (1/75) and HPV 66 (1/75). E2 disruption was detected in 56.3% of HPV 16 and in 40% of HPV 18 positive tumors. C-myc amplification was detected in 29.4% of cases, while k-ras mutations in 30.7%. There was no significant trend for HPV infection in tumors harboring either k-ras or c-myc alterations. This study demonstrates HPV DNA and viral integration in colorectal tumors, suggesting a potential role of this virus in colorectal carcinogenesis. There was no concurrence, however, of k-ras and c-myc activation with viral infection.
C1 [Perez, Orlando Luis] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60 and 118 street, PC B1900 La Plata, Buenos Aires, Argentina.
[Barbisan, Gisela] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60 and 118 street, PC B1900 La Plata, Buenos Aires, Argentina.
[Ottino, Anabel] Interzonal Hospital of San Martin, Service of Pathology, 1791 1st street, PC B1900 La Plata, Buenos Aires, Argentina.
[Pianzola, Horacio] Interzonal Hospital of San Martin, Service of Pathology, 1791 1st street, PC B1900 La Plata, Buenos Aires, Argentina.
[Golijow, Daniel Carlos] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60 and 118 street, PC B1900 La Plata, Buenos Aires, Argentina.
RP Perez, OL (reprint author), University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), PC B1900 La Plata, Argentina.
EM perezlo@gmail.com
CR Ferlay J, Bray F, Pisani P et al, 2004, GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide, IARC Cancer- Base N° 5. IARC, Lyon
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Bodaghi S, Yamanegi K, Xiao SY, 2005, Colorectal papillomavirus infection in patients with colorectal cancer. Clin Cancer Res 11:2862–2867
Yu HG, Shun LB, Luo HS et al, 2002, Deletion of the FHIT gene in human colorectal cancer is independent of high-risk HPV infection. Int J Colorectal Dis 17:396–401
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zur Hausen H, 1999, Viruses in human cancers. Eur J Cancer 35:1878–1885
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Ferber MJ, Thorland EC, Brink AA et al, 2003, Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma. Oncogene 22:7233–7242
Chakrabarti O, Krishna S, 2003, Molecular interactions of ‘high risk’ human papillomaviruses E6 and E7 oncoproteins: implications for tumour progression. J Biosci 28:337–348
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Badaracco G, Venuti A, Sedati A et al, 2002, HPV16 and HPV18 in genital tumors: significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol 67:574–582
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Herrick J, Conti C, Teissier S et al, 2005, Genomic organization of amplified MYC genes suggests distinct mechanisms of amplification in tumorigenesis. Cancer Res 65:1174–1179
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2010
VL 16
IS 3
BP 461
EP 468
DI 10.1007/s12253-010-9246-x
PG 8
ER
PT J
AU Fauzee, JSN
Pan, J
Wang, Yl
AF Fauzee, Jasmine Selimah Nilufer
Pan, Juan
Wang, Ya-lan
TI PARP and PARG Inhibitors—New Therapeutic Targets in Cancer Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PARP. PARG; PARP inhibitors; PARG inhibitors
ID PARP. PARG; PARP inhibitors; PARG inhibitors
AB Today, the number of cancer patients throughout the world is increasing alarmingly and as per the World Health Organisation (WHO) data and statistics the prediction for the year 2020 will be 15 million new cases as compared to only 10 million cases in year 2000 leaving us dumbfounded. A lot of effort has been put in by researchers and scientists over decades to find drugs helpful in the treatment of cancers for the benefit of patients—The latest being the Poly ADP-ribose polymerase (PARP) and the Poly ADP-ribose glycohydrolase (PARG) inhibitors. This review highlights their mechanism of action under the rationale of their use and current development in the field of cancer.
C1 [Fauzee, Jasmine Selimah Nilufer] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Pan, Juan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Wang, Ya-lan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
RP Wang, Yl (reprint author), Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
EM wangyalan074@126.com
CR D’amours D, Desnoyers S, D’silva I, Poirier GG, 1999, Poly, ADP-ribosyl)ation reactions in the regulation of nuclear functions. J Biochem 342:249–268
Parise RA, Shawaqfeh M, Egorin MJ, Beumer JH, 2008, Liquid chromatography-mass spactometric assay for quantitation in human plasma of ABT-888, an orally available, small molecule inhibitor of poly, ADP-ribose, polymerase. J Chromatogr B Analyt Technol Biomed Life Sci 872(1–2):141– 147
Hochegger H, Dejsuphong D, Fukushima T, Morrison C et al, 2006, Parp-1 protects homologous recombination from interferenve by Ku and Ligase IV in vertebrate cells. EMBO J 25:1305– 1314
Virag L, Szabo C, 2002, The therapeutic potential of poly, ADPribose, polymerase inhibitors. Pharmacol Rev 54:375–429
Meyer RG, Meyer-Ficca ML, Jacobson EL, Jacobson MK, 2003, Human poly, ADP-ribose, glycohydrolase, PARG, gene and the common promoter sequence it shares with inner mitochondrial membrane translocase 23, TIM23). Gene 314:181–190
Koh DW, Lawler AM, Poitras MF et al, 2004, Failure to degrade poly, ADP-ribose, increased sensitivity to cytotoxicity and early embryonic lethality. PNAS 101(51):17699–17704
Cortes U, Tong WM, Coyle DL et al, 2004, Depletion of the 110-Kilodalton isoform of poly, ADP-ribose, glycohydrolase increases sensitivity to genotoxic and endotoxic stress in mice. MCB 24(16):7163–7178
Poitras MF, Koh DW, Yu SWet al, 2007, Spatial and functional relationship between poly, ADP-ribose, polymerase-1 and Poly, ADP-ribose, glycohydrolase in the brain. Neuroscience 148, 1):198–211
Miwa M, Matsutani, 2007, PolyADP-ribosylation and cancer. Cancer Sci 98(10):1528–1535
Blenn C, Althaus FR, Manlanga M, 2006, Poly, ADP-ribose, glycohydrolase silencing protects against H2O2-induced cell death. J Biochem 396:419–429
Ratnam K, Low JA, 2007, Current development of clinical poly, ADP-ribose, inhibitor in oncology. Clin Cancer Res 13, 5):1383–1388
Decker P, Miranda EA, De Murcia G, Muller S, 1999, An improved nonisotopic test to screen a large series of new inhibitor molecules of poly, ADP-ribose, polymerase activity for therapeutic applications. Clin Cancer Res 5:1169–1172
Cuzzocrea S, Paola RD, Mazzon E et al, 2005, PARG activity mediates intestinal injury induced by splanchnic artery occlusion and reperfusion. FASEB J 19:558–566
Plummer R, Jones C, Middleton M et al, 2008, Phase I study of the poly, ADP-ribose, polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced Solid Tumors. Clin Cancer Res 14(23):7917–7923
Valenzuela MT, Guerrerro R, Nunez MI et al, 2002, PARP-1 modifies the effectiveness of P53 mediated DNA damage response. Oncogene 21(7):1108–1116
Oei SL, Ziegler M, 2000, ATP for the DNA ligation step in base excision repair is generated from poly, ADP-ribose). J Biol Chem 275:23234–23239
McCabe N, Turner NC, Lord CJ et al, 2006, Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly, ADP-ribose, polymerase inhibition. Cancer Res 66(16):8109–8115
Eguchi Y, Shimizu S, Tsujimoto Y, 1997, Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57:1835–1840
Kumari SR, Mendoza-Alvarez H, Alvarez-Gonzalez R, 1998, Functional interactions of p53 with poly(ADP-ribose, polymerase, PARP, during apoptosis following DNA damage: covalent poly(ADP-ribosyl)ation of p53by exogenous PARP and noncovalent binding of p53 to the Mr 85,000 proteolytic fragment1. Cancer Res 58:5075–5078
Affar EB, Germain M, Winstall E et al, 2001, Caspase-3- mediated processing of poly, ADP-ribose, glycohydrolase during apoptosis. JBC 276(4):2935–2942
Koh DW, Dawson TM, Dawson VL, 2005, Mediation of cell death by Poly, ADP-ribose)-1. Pharmacol Res 52(1):5–14
Bhaskara, et al, 2009, Differrential PARP cleavage: an indication for existence of multiple forms of cell death in human gilomas. Neurology India 57(3)
Hung Q, Wu YT, Tan HL, Ong CN, Shen HM, 2009, A novel function of PARP-1 in modulation of autophagy and necrosis under oxidative stress. Cell Death Diff 16:264–277
Lee Y, Shacter E, 1999, Oxidative stress inhibits apoptosis in human lymphoma cells. J Bio Chem 274:19792–19798
Walisser JA, Thies RC, 1999, Poly, ADP-ribose, polymerase inhibition in oxidant stressed endothelial cells prevents oncosis and permits caspase activation and apoptosis. Exp Cell Res 251, 12):401–413
Mathews MT, Berk BC, 2008, PARP-1 inhibition prevents oxidative and nitrosative stress–induced endothelial cell death via transactivation of the VEGF receptor 2. Arterioscler Thromb Vasc Biol 28:711–717
Kovacs K, Toth A, Deres P et al, 2006, Critical role of PI3- kinase/Akt activation in the PARP inhibitor induced heart function recovery during ischemia–reperfusion. Biochem Pharmacol 71(4):441–452
Klaidman L, Morales M, Kem S et al, 2003, Nicotinamide offers multiple protective mechanisms in stroke as a precursor for NAD+, as a PARP inhibitor and by partial restoration of mitochondrial function. Pharmacology 69(3):150–157
Filipovic DM, Meng X, Reeves WB, 1999, Inhibition of PARP prevents oxidant-induced necrosis but not apoptosis in LLC-PK1 cells. Am J Physiol Renal Physiol 277:428–436
Roesner JP, Vagts DA, Iber T et al, 2006, Protective effects of PARP inhibition on liver microcirculation and function after haemorrhagic shock and resuscitation in male rats. Intensive Care Med 32(10):1649–1657
Oku H, Goto W, Tsujimoto M et al, 2003, Effects of Poly(ADPribose, polymerase, PARP, Inhibitor on NMDA-induced retinal injury. Invest Ophthalmol Vis Sci 44: E-Abstract 27
Charron MJ, Bonner-Weir S, 1999, Implicating PARP and NAD+ depletion in type I diabetes. Nat Med 5:269–270
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 469
EP 478
DI 10.1007/s12253-010-9266-6
PG 10
ER
PT J
AU Wittschieber, D
Kollermann, J
Schlomm, Th
Sauter, G
Erbersdobler, A
AF Wittschieber, Daniel
Kollermann, Jens
Schlomm, Thorsten
Sauter, Guido
Erbersdobler, Andreas
TI Nuclear Grading Versus Gleason Grading in Small Samples Containing Prostate Cancer: A Tissue Microarray Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Gleason grading; Fuhrman nuclear grading; Prognosis; TMA
ID Prostate cancer; Gleason grading; Fuhrman nuclear grading; Prognosis; TMA
AB In this study we addressed the question whether nuclear grading in very small samples of prostate cancer would provide additional prognostic information as compared to Gleason grading. Therefore, a tissue microarray (TMA) was constructed comprising a total number of 3,261 prostate cancers. Blinded for all clinical and pathological data, the TMA spots (diameter 0.6 mm) containing cancer were graded with two systems: First, for nuclear features according to a modified Fuhrman grading system, and second, by using a simplified Gleason system. The results were compared with tumour stage, tumour grade and follow-up data. Although nuclear grading could easily be performed on the TMA spots, no correlation was found with tumour stage, grade or PSA recurrence after prostatectomy. However, Gleason grading, even when performed on the small TMA spots, provided significant prognostic information. Correlation with Gleason scores determined in the complete prostatectomy specimens showed moderate agreement in low-grade (score≤6) or intermediate (score=7) tumours, but poor agreement with high-grade (score≥8) tumours. In conclusion, the Fuhrman grading of prostate cancer does not appear to be of any prognostic importance so the Gleason grading remains the system of choice, even in tumour specimens smaller than 1 mm.
C1 [Wittschieber, Daniel] Charite University Hospital, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
[Kollermann, Jens] University Medical Center, Institute of PathologyHamburg-Eppendorf, Germany.
[Schlomm, Thorsten] University Medical Center, Martini-Clinic, Prostate Cancer CenterHamburg-Eppendorf, Germany.
[Sauter, Guido] University Medical Center, Institute of PathologyHamburg-Eppendorf, Germany.
[Erbersdobler, Andreas] Charite University Hospital, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
RP Wittschieber, D (reprint author), Charite University Hospital, Institute of Pathology, 10117 Berlin, Germany.
EM daniel.wittschieber@charite.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 479
EP 484
DI 10.1007/s12253-010-9270-x
PG 6
ER
PT J
AU Anghel, A
Narita, D
Seclaman, E
Popovici, E
Anghel, M
Tamas, L
AF Anghel, Andrei
Narita, Diana
Seclaman, Edward
Popovici, Emilian
Anghel, Mariana
Tamas, Liviu
TI Estrogen Receptor Alpha Polymorphisms and the Risk of Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute myeloid leukemia; Bladder; Breast; Colorectal; Hepatocellular carcinomas; Susceptibility; Estrogen receptor alpha gene; Single nucleotide polymorphisms
ID Acute myeloid leukemia; Bladder; Breast; Colorectal; Hepatocellular carcinomas; Susceptibility; Estrogen receptor alpha gene; Single nucleotide polymorphisms
AB Estrogens represent risk factors for endocrinerelated cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients—103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)—and 114 healthy controls using hybridization probes. We performed Armitage` s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast=4×10-5; p-trend cancers=1×10-5); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p=1×10-4); for rs2228480, the heterozygous frequency was higher for cancer groups (p=0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplo types T-A of rs2234693&rs9340799 and G-C of rs2228480&rs3798577 showed a trend to be higher represented in breast cancers; T allele of rs2234693 was higher expressed in breast, colon cancers and leukemia; rs2077647 was associated with colon (p=0.008, C-risk allele) and bladder (p=0.01, T-risk allele) cancers. We concluded that ESR1 polymorphisms may have distinct impact in carcinogenesis and further genotyping will establish whether these findings remain significant in larger cohorts.
C1 [Anghel, Andrei] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu 2A, 300041 Timisoara, Romania.
[Narita, Diana] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu 2A, 300041 Timisoara, Romania.
[Seclaman, Edward] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu 2A, 300041 Timisoara, Romania.
[Popovici, Emilian] University of Medicine and Pharmacy, Eftimie Murgu 2A, 300041 Timisoara, Romania.
[Anghel, Mariana] University of Medicine and Pharmacy, Eftimie Murgu 2A, 300041 Timisoara, Romania.
[Tamas, Liviu] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu 2A, 300041 Timisoara, Romania.
RP Narita, D (reprint author), University of Medicine and Pharmacy, Biochemistry Department, 300041 Timisoara, Romania.
EM diana_narita@yahoo.com;biochim@umft.ro
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 485
EP 496
DI 10.1007/s12253-010-9263-9
PG 12
ER
PT J
AU Michailidi, Ch
Giaginis, C
Stolakis, V
Alexandrou, P
Klijanienko, J
Delladetsima, I
Chatzizacharias, N
Tsourouflis, G
Theocharis, S
AF Michailidi, Christina
Giaginis, Costas
Stolakis, Vassilios
Alexandrou, Paraskevi
Klijanienko, Jerzy
Delladetsima, Ioanna
Chatzizacharias, Nicolaos
Tsourouflis, Gerasimos
Theocharis, Stamatios
TI Evaluation of FAK and Src Expression in Human Benign and Malignant Thyroid Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Focal Adhesion Kinase (FAK); Src; Thyroid cancer; immunohistochemistry; Clinicopathological parameters; Diagnosis
ID Focal Adhesion Kinase (FAK); Src; Thyroid cancer; immunohistochemistry; Clinicopathological parameters; Diagnosis
AB Focal Adhesion Kinase (FAK) and Src have been reported to regulate tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate by immunohistochemistry the clinical significance of FAK and Src expression in 108 patients with benign and malignant thyroid lesions. Total FAK expression provided a distinct discrimination between malignant and benign (p=0.00001), as well as between papillary carcinoma and hyperplastic nodules thyroid lesions (p=0.00005), being also associated with follicular cells’ proliferative capacity (p=0.0003). In malignant thyroid lesions, total FAK expression was associated with tumor size (p=0.0455), and presence of capsular (p=0.0102) and lymphatic (p=0.0173) invasion. Total Src expression was borderline increased in cases of papillary carcinoma compared to hyperplastic nodules (p=0.0993), being also correlated with tumor size (p=0.0169). FAK and Src expression was ascribed to a significant extent to the phosphorylated forms of the enzymes, which provided a better discrimination between malignant and benign thyroid lesions. The current data revealed that FAK and to a lesser extent Src expression could be considered of clinical utility in thyroid neoplasia with potential use as therapeutic targets.
C1 [Michailidi, Christina] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Giaginis, Costas] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Stolakis, Vassilios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Klijanienko, Jerzy] Institut Curie, Department of PathologyParis, France.
[Delladetsima, Ioanna] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Chatzizacharias, Nicolaos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Tsourouflis, Gerasimos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Theocharis, Stamatios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
RP Theocharis, S (reprint author), University of Athens, Medical School, Department of Forensic Medicine and Toxicology, GR11527 Athens, Greece.
EM theocharis@ath.forthnet.gr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 497
EP 507
DI 10.1007/s12253-010-9269-3
PG 11
ER
PT J
AU Huang, Q
Xia, Z
You, Y
Pu, P
AF Huang, Qiang
Xia, Zhibo
You, Yongping
Pu, Peiyu
TI Wild Type p53 Gene Sensitizes Rat C6 Glioma Cells to HSV-TK/ACV Treatment In Vitro and In Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; wt-p53; HSV-TK/ACV; Suicide gene therapy; Combined gene therapy
ID Glioma; wt-p53; HSV-TK/ACV; Suicide gene therapy; Combined gene therapy
AB Suicide gene therapy using herpes simplex virusthymidine kinase (HSV-TK)/ganciclovir (GCV), has been extensively tested for the treatment of glioma. Our previous study showed that exogenous wild type p53 (wt-p53) enhanced the anti-tumor effect of HSV-TK/GCV therapy. However, the use of GCV is hindered by its low penetration to the brain and its toxity when used at higher dose. In the present study, we used another pro-drug, acyclovir (ACV), and examined the therapeutic efficacy of HSV-TK/ACV combining with wt-p53 in C6 glioma cells. We observed that wt-p53 combined with HSV-TK/ACV resulted in the super-additive anti-tumor effect in vitro. Exogenous wt-p53 significantly enhanced the sensitivity of TK positive C6 cells to ACV in vitro. Our in vivo experiment demonstrated that the effect of wt-p53 and HSV-TK/ACV combination therapy was better than that of HSV-TK/ACV alone. The survival time of tumor-bearing rats treated with wt-p53 in combination with HSV-TK/ACV was also significantly prolonged than those treated with HSV-TK/ACV alone. These results suggest that wt-p53 can enhance the therapeutic efficacy of HSV-TK/ACV both in vitro and in vivo. These findings are considerably valuable with the respect of using less toxic ACV as prodrug. This novel strategy could provide benefit to HSV-TK/prodrug gene therapy.
C1 [Huang, Qiang] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
[Xia, Zhibo] The First Affiliated Hospital of Sun Yat-sen University, Department of Neurosurgery, 58 Zhongshan Road II, 510080 Guangzhou, Guangdong, China.
[You, Yongping] The First Affiliated Hospital of Nanjing Medical University, Department of Neurosurgery, 210029 Nanjing, China.
[Pu, Peiyu] Tianjin Medical University General Hospital, Department of Neurosurgery, 154 Anshan Road, 300052 Tianjin, China.
RP Pu, P (reprint author), Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
EM pupeiyu33@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 509
EP 514
DI 10.1007/s12253-009-9240-3
PG 6
ER
PT J
AU Ren, HZ
Wang, JSh
Wang, P
Pan, Gq
Wen, JF
Fu, H
Shan, Xz
AF Ren, Hong-Zheng
Wang, Jin-Sheng
Wang, Peng
Pan, Guo-qing
Wen, Ji-Fang
Fu, Hua
Shan, Xu-zheng
TI Increased Expression of Prohibitin and its Relationship with Poor Prognosis in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prohibitin; Esophageal squamous cell carcinoma; Prognosis; Immunohistochemistry
ID Prohibitin; Esophageal squamous cell carcinoma; Prognosis; Immunohistochemistry
AB Prohibitin, a potential tumor suppressor, has been shown to be an anti- proliferative protein, a regulator of cell-cycle progression and in apoptosis. Recently, it was found to be over-expressed in breast cancer and gastric cancer, and it has been suggested as a biomarker in those diseases. To clarify the role and the prognostic significance of prohibitin expression in esophageal squamous cell carcinoma (ESCC), we analyzed the expression in ESCC and their corresponding nonneoplastic epithelia tissues by immunohistochemistry(IHC), Western blotting and realtime quantitative reverse transcription polymerase chain reaction(QRT-PCR).The relationship between prohibitin expression and clinicopathological variables was examined by statistical analysis. The findings suggested the upregulation of prohibitin play an important role in the carcinogenesis of ESCC. The over-expression of prihibitin was significantly correlated with the depth of tumor, lymph node metastasis, distant metastasis, lymphatic invasion and vascular invasion of ESCC. These results suggested that prohibitin(+), lymph node metastasis and distant metastasis could be the independent risk factors for worse prognosis in ESCC patients.
C1 [Ren, Hong-Zheng] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Wang, Jin-Sheng] Changzhi Medical College, Department of PathologyChangzhi, China.
[Wang, Peng] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Pan, Guo-qing] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Wen, Ji-Fang] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Fu, Hua] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Shan, Xu-zheng] Central South University, Public Health College, Department of Health Statistics and EpidemiologyChangsha, China.
RP Wen, JF (reprint author), Central South University, Xiangya Basic Medical College, Department of Pathology, Changsha, China.
EM jifangwen@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 515
EP 522
DI 10.1007/s12253-009-9242-1
PG 8
ER
PT J
AU Yamada, Shi
Yanamoto, S
Kawasaki, G
Mizuno, A
Nemoto, KT
AF Yamada, Shin-ichi
Yanamoto, Souichi
Kawasaki, Goro
Mizuno, Akio
Nemoto, K Takayuki
TI Overexpression of Cortactin Increases Invasion Potential in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cortactin; Invasion; Metastasis; RNA interference; Oral squamous cell carcinoma
ID Cortactin; Invasion; Metastasis; RNA interference; Oral squamous cell carcinoma
AB Cortactin, an F-actin binding protein, stabilizes F-actin networks and promotes actin polymerization by activating the Arp2/3 complex. Overexpression of cortactin has been reported in several human cancers. Cortactin stimulates cell migration, invasion, and experimental metastasis. However, the underlying mechanism is not still understood. In the present study, we therefore evaluated the possibility that cortactin could be appropriate as a molecular target for cancer gene therapy. In 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens, cortactin expression was evaluated by immunological analyses, and the correlations of the overexpression of cortactin with clinicopathologic factors were evaluated. Overexpression of cortactin was detected in 32 of 70 oral squamous cell carcinomas; significantly more frequently than in normal oral mucosa. Cortactin overexpression was more frequent in higher grade cancers according to T classification, N classifications, and invasive pattern. Moreover, RNAi-mediated decrease in cortactin expression reduced invasion. Downregulation of cortactin expression increased the expression levels of E-cadherin, β-catenin, and EpCAM. The siRNA of cortactin also reduced PTHrP expression via EGF signaling. These results consistently indicate that the overexpression of cortactin is strongly associated with an aggressive phenotype of oral squamous cell carcinoma. In conclusion, we propose that cortactin could be a potential molecular target of gene therapy by RNAi targeting in oral squamous cell carcinoma.
C1 [Yamada, Shin-ichi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawasaki, Goro] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Mizuno, Akio] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Nemoto, K Takayuki] Nagasaki University Graduate School of Biomedical Sciences, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Department of Oral Molecular Biology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Yamada, Shi (reprint author), Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 852-8588 Nagasaki, Japan.
EM shinshin@nagasaki-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 523
EP 531
DI 10.1007/s12253-009-9245-y
PG 9
ER
PT J
AU Naidu, R
Har, ChY
Taib, AMN
AF Naidu, Rakesh
Har, Cheng Yip
Taib, Aishah Mohd Nur
TI Genetic Polymorphisms of Paraoxonase 1 (PON1) Gene: Association Between L55M or Q192R with Breast Cancer Risk and Clinico-Pathological Parameters
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Paraoxonase 1; Polymorphism
ID Breast cancer; Paraoxonase 1; Polymorphism
AB The aim of the present study was to evaluate the association between the paraoxonase 1 (PON1) L55M and Q192R polymorphisms and breast cancer risk as well as clinico-pathological characteristics of the patients. Genotyping of these polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The genotype (P=0.023) and allele (P=0.008) frequencies of L55M polymorphism were significantly different between the breast cancer cases and normal individuals. However, the distribution of genotype (P=0.333) and allele (P=0.163) frequencies of Q192R polymorphism showed lack of statistical significance. Women who were MM homozygotes (OR=2.229; 95% CI, 1.219–4.075) and carriers of M allele genotype (OR=1.429; 95% CI, 1.035–1.974) or M allele (OR=1.397; 95% CI, 1.093–1.785) were associated with increased risk of breast cancer. However, women who were heterozygous (OR=0.793; 95% CI, 0.567–1.110) or homozygous (OR=0.746; 95% CI, 0.407–1.370) for R allele or carriers of R allele (OR=0.838; 95%, 0.654–1.074) were not associated with breast cancer risk. The M allele genotype was significantly associated with estrogen receptor negativity (P=0.046) and nodal involvement (P=0.004) but R allele genotype was not associated with any of the clinico-pathological characteristics. In conclusion, our findings suggest that the polymorphic variant of L55M polymorphism could be a useful genetic marker for tumor prognosis and to identify women who might be at greater risk of developing breast cancer in a hospital-based Malaysian population.
C1 [Naidu, Rakesh] Monash University, Sunway Campus, School of Medicine and Health Sciences, Jalan Lagoon Selatan, 46150 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
[Har, Cheng Yip] Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Surgery, 50603 Kuala Lumpur, Malaysia.
[Taib, Aishah Mohd Nur] Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Surgery, 50603 Kuala Lumpur, Malaysia.
RP Naidu, R (reprint author), Monash University, Sunway Campus, School of Medicine and Health Sciences, 46150 Bandar Sunway, Malaysia.
EM kdrakeshna@hotmail.com
CR Mackness B, Durrington PN, Mackness MI, 1998, Human serum paraoxonase. Gen Pharmacol 31:329–336
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Aviram M, Hardak E, Vaya J et al, 2000, Human serum paraoxonases, PON1, Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101:2510–2517
Akcay MN, Yilmaz I, Polat MF et al, 2003, Serum paraoxonase levels in gastric cancer. Hepatogastroenterology 50:cclxxiii–v
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 533
EP 540
DI 10.1007/s12253-010-9267-5
PG 8
ER
PT J
AU Valcz, G
Sipos, F
Krenacs, T
Molnar, J
Patai, V
Leiszter, K
Toth, K
Solymosi, N
Galamb, O
Molnar, B
Tulassay, Zs
AF Valcz, Gabor
Sipos, Ferenc
Krenacs, Tibor
Molnar, Jeannette
Patai, V Arpad
Leiszter, Katalin
Toth, Kinga
Solymosi, Norbert
Galamb, Orsolya
Molnar, Bela
Tulassay, Zsolt
TI Elevated Osteopontin Expression and Proliferative/Apoptotic Ratio in the Colorectal Adenoma–Dysplasia–Carcinoma Sequence
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Proliferative/apoptotic ratio; Adenoma–dysplasia–carcinoma sequence; Gene expression; Tissue microarray
ID Proliferative/apoptotic ratio; Adenoma–dysplasia–carcinoma sequence; Gene expression; Tissue microarray
AB Colorectal cancer progression is characterized by altered epithelial proliferation and apoptosis and by changed expression of tumor development regulators.Our aims were to determine the proliferative/apoptotic epithelial cell ratio (PAR) in the adenoma–dysplasia–carcinoma sequence (ADCS), and to examine its association with osteopontin (OPN), a previously identified protein product related to cancer development. One mm diameter cores from 13 healthy colons, 13 adenomas and 13 colon carcinoma samples were included into a tissue microarray (TMA) block. TUNEL reaction and Ki-67 immunohistochemistry were applied to determine the PAR. The osteopontin protein was also immunodetected. Stained slides were semiquantitatively evaluated using digital microscope and statistically analyzed with logistic regression and Fisher’s exact test. The PAR continuously increased along the ADCS. It was significantly (p<0.001) higher in cancer epithelium (8.84±7.01) than in adenomas (1.40±0.78) and in normal controls (0.89±0.21) (p<0.001). Also, significant positive correlation was observed between elevated PAR and the expression of osteopontin. Cytoplasmic OPN expression was weak in healthy samples. In contrast, cytoplasmic immunoreaction was moderately intensive in adenomas, while in colon cancer strong, diffuse cytoplasmic immune staining was detected. Increasing PAR and OPN expression along ADCS may help monitoring colorectal cancer progression. The significantly elevated OPN protein levels we found during normal epithelium to carcinoma progression may contribute to the increased fibroblast–myofibroblast transition determining stem cell niche in colorectal cancer.
C1 [Valcz, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Molnar, Jeannette] National Institute of Food and Nutrition ScienceBudapest, Hungary.
[Patai, V Arpad] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Leiszter, Katalin] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Solymosi, Norbert] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
RP Valcz, G (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM valczg@yahoo.com
CR Burgess AW, 1998, Growth control mechanisms in normal and transformed intestinal cells. Philos Trans R Soc Lond B Biol Sci 353:903–909
Walker MR, Patel KK, Stappenbeck TS, 2009, The stem cell niche. J Pathol 217:169–180
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 541
EP 545
DI 10.1007/s12253-010-9260-z
PG 5
ER
PT J
AU Jaberipour, M
Habibagahi, M
Hosseini, A
Habibabad, RS
Talei, AAR
Ghaderi, A
AF Jaberipour, Mansooreh
Habibagahi, Mojtaba
Hosseini, Ahmad
Habibabad, Rezai Saadat
Talei, Abd-Al-Rasoul
Ghaderi, Abbas
TI Increased CTLA-4 and FOXP3 Transcripts in Peripheral Blood Mononuclear Cells of Patients with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; CTLA-4 and FOXP3
ID Breast cancer; CTLA-4 and FOXP3
AB Generation of Regulatory T cells (Tregs) is known to play a major role in progression and modulation of the immune escape mechanisms in cancer. These cells express Forkhead/winged helix transcription factor (FOXP3) and also Cytotoxic T-lymphocyte antigen-4 (CTLA-4), as a negative regulatory molecule which, is a potential target for immunotherapy. We, therefore, evaluated FOXP3 and CTLA-4 transcripts in the peripheral blood mononuclear cells from 55 women with histologically-confirmed infiltrating ductal carcinoma of the breast. Blood samples from 40 healthy volunteer women without a history of malignancies or autoimmune disorders were also obtained as a control. The abundance of FOXP3 and CTLA-4 gene transcripts was determined by quantitative real-time PCR (qRT-PCR). Compared to healthy individuals, significantly higher amounts of these transcripts were found in the mononuclear cells from breast cancer patients. Also, a significant correlation was found between CTLA-4 and FOXP3 expressions in a group of patients. Among patients with early stage, nonmetastatic or low-grade disease, the relative expression of CTLA-4 was about 10-fold as much as in the control group. These patients also showed a significant increase, more than 10 fold, in mean relative FOXP3 expression. The results of this investigation point to functional activity of Treg cells in early stages of breast cancer, a finding which emphasizes the significance of Tregs as an imminent target for breast cancer immunotherapy.
C1 [Jaberipour, Mansooreh] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Habibagahi, Mojtaba] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Hosseini, Ahmad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Habibabad, Rezai Saadat] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Talei, Abd-Al-Rasoul] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Habibagahi, M (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM agahim@sums.ac.ir
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 547
EP 551
DI 10.1007/s12253-010-9256-8
PG 5
ER
PT J
AU Bircan, A
Bircan, S
Kapucuoglu, N
Songur, N
Ozturk, O
Akkaya, A
AF Bircan, Ahmet
Bircan, Sema
Kapucuoglu, Nilgun
Songur, Necla
Ozturk, Onder
Akkaya, Ahmet
TI Maspin, VEGF and p53 Expression in Small Biopsies of Primary Advanced Lung Cancer and Relationship with Clinicopathologic Parameters
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Maspin; VEGF; p53; Biopsy; Immunohistochemistry
ID Lung cancer; Maspin; VEGF; p53; Biopsy; Immunohistochemistry
AB Maspin, one of the serine protease inhibitors, has been shown to inhibit tumor progression and metastasis. We aimed to investigate maspin, p53 and VEGF expression in patients with squamous cell carcinoma (SCC), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). The study included 28 SCC, 18 AC, 17 SCLC biopsy samples. We used the streptavidin biotin immunoperoxidase method to test for maspin, p53 and VEGF antibodies. Medical records of these patients were reviewed from archival files. Cytoplasmic maspin expression was detected in 89.3%, 77.8%, 52.9% of SCC, AC and SCLC, respectively. The rate was significantly higher in non-small cell lung cancer (NSCLC) and SCC than SCLC (p=0.013, p=0.021, respectively). The mean percentages of maspin expression were significantly higher in NSCLC, SCC and AC than in SCLC (p=0.0001, p=0.0001, p=0.038, respectively). In ACs, maspin and p53 expressions were correlated, although this was not statistically significant (p=0.053, r=0.464), and maspin positive cases had a significantly higher T status compared to negative cases (p=0.036). In SCC, the stage of disease was positively correlated with p53 (p=0.007, r=0.536) and negatively correlated with VEGF expression (p=0.013, r=−0.498). Multivariate analysis demonstrated that stage of disease was a significant independent prognostic parameter in NSCLC (95% confidence interval: 1.067–3.969; p=0.031). Although maspin expression is higher in SCC and AC, and is related with higher T status in AC, our data did not indicate its prognostic significance. Larger scale studies are needed to reveal the exact role of maspin in lung cancer pathogenesis.
C1 [Bircan, Ahmet] Suleyman Demirel University, Faculty of Medicine, Department of Pulmonary Medicine, 32260 Cunur, Isparta, Turkey.
[Bircan, Sema] Suleyman Demirel University, Faculty of Medicine, Department of PathologyIsparta, Turkey.
[Kapucuoglu, Nilgun] Suleyman Demirel University, Faculty of Medicine, Department of PathologyIsparta, Turkey.
[Songur, Necla] Suleyman Demirel University, Faculty of Medicine, Department of Pulmonary Medicine, 32260 Cunur, Isparta, Turkey.
[Ozturk, Onder] Suleyman Demirel University, Faculty of Medicine, Department of Pulmonary Medicine, 32260 Cunur, Isparta, Turkey.
[Akkaya, Ahmet] Suleyman Demirel University, Faculty of Medicine, Department of Pulmonary Medicine, 32260 Cunur, Isparta, Turkey.
RP Bircan, A (reprint author), Suleyman Demirel University, Faculty of Medicine, Department of Pulmonary Medicine, 32260 Cunur, Turkey.
EM ahbircan@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 553
EP 561
DI 10.1007/s12253-010-9259-5
PG 9
ER
PT J
AU Eren, F
Akkiprik, M
Atug,
Sonmez, O
Tahan, G
Ozdemir, F
Hamzaoglu, H
Celikel, A
Imeryuz, N
Avsar, E
Ozer, A
AF Eren, Fatih
Akkiprik, Mustafa
Atug, Ozlen
Sonmez, Ozgur
Tahan, Gulgun
Ozdemir, Filiz
Hamzaoglu, Over Hulya
Celikel, Ataizi Cigdem
Imeryuz, Nese
Avsar, Erol
Ozer, Ayse
TI R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; Codon 72 polymorphism; Colorectal cancer; Ulcerative colitis; Colectomy; Steroid; Family history
ID p53; Codon 72 polymorphism; Colorectal cancer; Ulcerative colitis; Colectomy; Steroid; Family history
AB P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR=3.03; 95%CI=1.91–2.40; p=0.003), but only modest association with UC (OR=1.61; 95%CI=0.98–2.65; p=0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR=8.0; 95%CI=1.68–38.08, p=0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR=17.77; 95%CI=0.98–323.34, p=0.012) and steroid use (OR=10.14; 95%CI=2.63–39.12, p=0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.
C1 [Eren, Fatih] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad., No: 49, Haydarpasa, 34668 Istanbul, Turkey.
[Akkiprik, Mustafa] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad., No: 49, Haydarpasa, 34668 Istanbul, Turkey.
[Atug, Ozlen] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Sonmez, Ozgur] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad., No: 49, Haydarpasa, 34668 Istanbul, Turkey.
[Tahan, Gulgun] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Ozdemir, Filiz] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Hamzaoglu, Over Hulya] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Celikel, Ataizi Cigdem] Marmara University, School of Medicine, Department of PathologyAltunizade, Turkey.
[Imeryuz, Nese] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Avsar, Erol] Marmara University, Gastroenterology InstituteBasibuyuk, Turkey.
[Ozer, Ayse] Marmara University, School of Medicine, Department of Medical Biology, Tibbiye Cad., No: 49, Haydarpasa, 34668 Istanbul, Turkey.
RP Akkiprik, M (reprint author), Marmara University, School of Medicine, Department of Medical Biology, 34668 Istanbul, Turkey.
EM akkiprik@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 563
EP 568
DI 10.1007/s12253-010-9255-9
PG 6
ER
PT J
AU Bektas, S
Bahadir, B
Ucan, HB
Ozdamar, OS
AF Bektas, Sibel
Bahadir, Burak
Ucan, Hamdi Bulent
Ozdamar, Oguz Sukru
TI CD24 and Galectin-1 Expressions in Gastric Adenocarcinoma and Clinicopathologic Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD24; Clinicopathologic variables; Galectin-1; Gastric adenocarcinoma; Prognosis
ID CD24; Clinicopathologic variables; Galectin-1; Gastric adenocarcinoma; Prognosis
AB CD24 and galectin-1 expression in gastric adenocarcinoma and their clinicopathologic significance remained largely unknown. We aimed to evaluate expressions and staining intensities of CD24 and galectin-1 in gastric adenocarcinoma and to investigate the interrelation with clinicopathologic parameters including survival. 93 cases with gastric adenocarcinoma were reevaluated histopathologically and immunohistochemistry was performed with antibodies against CD24 and galectin-1. Staining intensities of both markers in tumor cells and staining intensity of galectin-1 in tumor-associated stromal cells were scored semiquantitatively. The relationship between expression and staining intensity of CD24 and galectin-1 and clinicopathologic variables were assessed. CD24 staining intensity was associated with lymphovascular invasion (p=0.007), serosal invasion (p=0.001), stage (p=0.001) and lymph node metastasis (p=0.005). Galectin-1 staining intensity in tumor-associated stromal cells was associated with tumor location (p=0.031), lymphovascular invasion (p=0.001), perineural invasion (p=0.001), serosal invasion (p=0.001), differentiation (p=0.003), stage (p=0.001) and lymph node metastasis (p=0.001). Staining intensity of CD24 (p=0.019) and gal-1 (p=0.018) were associated with patient survival. Staining intensity of CD24 in tumor cells and galectin-1 in tumor-associated stromal cells were related with certain clinicopathologic variables. Our findings suggest that these markers are independent prognostic indicators of poor survival and may serve as useful targets for novel therapies.
C1 [Bektas, Sibel] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
[Bahadir, Burak] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
[Ucan, Hamdi Bulent] Zonguldak Karaelmas University, School of Medicine, Department of Surgery, 67600 Kozlu, Zonguldak, Turkey.
[Ozdamar, Oguz Sukru] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
RP Bektas, S (reprint author), Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Turkey.
EM sibel_bektas@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 569
EP 577
DI 10.1007/s12253-010-9248-8
PG 9
ER
PT J
AU Mahjour, BS
Ghaffarpasand, F
Fattahi, JM
Ghaderi, A
Fotouhi Ghiam, A
Karimi, M
AF Mahjour, Babak Seyed
Ghaffarpasand, Fariborz
Fattahi, Javad Mohammad
Ghaderi, Abbas
Fotouhi Ghiam, Alireza
Karimi, Mehran
TI Seroprevalence of Human Herpes Simplex, Hepatitis B and Epstein-Barr Viruses in Children with Acute Lymphoblastic Leukemia in Southern Iran
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute Lymphoblastic Leukemia (ALL); Epstein-Barr Virus (EBV); Hepatitis B Virus (HBV); Human Herpes Simplex Virus (HSV); Iran
ID Acute Lymphoblastic Leukemia (ALL); Epstein-Barr Virus (EBV); Hepatitis B Virus (HBV); Human Herpes Simplex Virus (HSV); Iran
AB To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age-sex matched healthy participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA) were measured by enzyme-linked immunosorbent assay (ELISA). There were 54 (60%) male and 36 (40%) female in both study groups with mean age of 8.47±3.61 and 8.61±2.84 years in case and control group respectively (P=0.812). The prevalence of antibodies against HBsAg (P=0.002), HSV1 (P<0.0001), VCA (P=0.021) and EA (P<0.0001) antigens of EBV were significantly higher in ALL patients. With the results of this study, we could not exclude a connection between these viral infections and later leukemogenesis in childhood ALL, although nor latent infection nor congenital infection cannot be excluded by this method.
C1 [Mahjour, Babak Seyed] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghaffarpasand, Fariborz] Fasa University of Medical SciencesFasa, Iran.
[Fattahi, Javad Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Fotouhi Ghiam, Alireza] McGill University, Douglas Hospital, Mental Health University InstituteMontreal, Quebec, Canada.
[Karimi, Mehran] Shiraz University of Medical Sciences, Nemazee Hospital, Hematology Research CenterShiraz, Iran.
RP Karimi, M (reprint author), Shiraz University of Medical Sciences, Nemazee Hospital, Hematology Research Center, Shiraz, Iran.
EM karimim@sums.ac.ir
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Gustafsson B, Huang W, Bogdanovic G, Gauffin F, Nordgren A, Talekar G, Ornelles DA, Gooding LR, 2007, Adenovirus DNA is detected at increased frequency in Guthrie cards from children who develop acute lymphoblastic leukaemia. Br J Cancer 97:992– 994
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Lehtinen M, Koskela P, Ogmundsdottir HM, Bloigu A, Dillner J, Gudnadottir M, Hakulinen T, Kjartansdottir A, Kvarnung M, Pukkala E, Tulinius H, Lehtinen T, 2003, Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring. Am J Epidemiol 158:207–213
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 579
EP 582
DI 10.1007/s12253-010-9258-6
PG 4
ER
PT J
AU Kakihana, K
Ohashi, K
Akiyama, H
Sakamaki, H
AF Kakihana, Kazuhiko
Ohashi, Kazuteru
Akiyama, Hideki
Sakamaki, Hisashi
TI Correlation Between Survival and Number of Mobilized CD34+ Cells in Patients with Multiple Myeloma or Waldenstrom Macroglobulinemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mobilized CD34+ cell number; Multiple myeloma; Waldenstrom macroglobulinemia; Autologous stem cell transplantation
ID Mobilized CD34+ cell number; Multiple myeloma; Waldenstrom macroglobulinemia; Autologous stem cell transplantation
AB High-dose chemotherapy followed by autologous stem cell transplantation is the established treatment for symptomatic multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). We retrospectively analyzed the impact of mobilized CD34+ cell number on clinical outcomes in patients with MM or WM who underwent autologous stem cell transplantation in our hospital from 1997 to 2007. A total of 39 patients were identified. All patients received peripheral stem cell support after a conditioning regimen. We defined patients with collection of a large number (≥ 8×106/kg) of CD34+ cells as super mobilizers (SM), and all others as normal mobilizers (NM). Although hematological engraftment was earlier in the SM group, overall survival did not differ significantly between groups (P=0.392). Likewise, no significant differences were seen in progression-free survival (P=0.201) or survival after relapse (P=0.330). In conclusion, our retrospective study could not find any correlation between survival and number of mobilized CD34+ cells, in contrast to previously reported results.
C1 [Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22, Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22, Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Akiyama, Hideki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22, Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22, Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Ohashi, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM k.ohashi@cick.jp
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Hiwase DK, Hiwase S, Bailey M et al, 2008, Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant 14:116–124
Bolwell BJ, Pohlman B, Rybicki L et al, 2007, Patients mobilizing large numbers of CD34+ cells, ‘super mobilizers’, have improved survival in autologous stem cell transplantation for lymphoid malignancies. Bone Marrow Transplant 40:437–441
Wang S, Nademanee A, Qian D et al, 2007, Peripheral blood hematopoietic stem cell mobilization and collection efficacy is not an independent prognostic factor for autologous stem cell transplantation. Transfusion 47:2207–2216
Galimberti S, Morabito F, Guerrini F et al, 2003, Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of autotransplanted multiple myeloma patients. Br J Haematol 120:405–412
Gordan LN, Sugrue MW, Lynch JW et al, 2003, Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation. Leuk Lymphoma 44:815–820
O’Shea D, Giles C, Terpos E et al, 2006, Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients. Bone Marrow Transplant 37:731–737
Krejci M, Buchler T, Hajek R et al, 2005, Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients. Bone Marrow Transplant 35:159–164
Wahlin A, Eriksson M, Hultdin M, 2004, Relation between harvest success and outcome after autologous peripheral blood stem cell transplantation in multiple myeloma. Eur J Haematol 73:263–268
Krejci M, Hajek R, Buchler T et al, 2007, Simple variables predict survival after autologous transplantation: a single centre experience in 181 multiple myeloma patients. Neoplasma 54:143–148
Dean R, Masci P, Pohlman B et al, 2005, Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival. Bone Marrow Transplant 36:1049–1052
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 583
EP 587
DI 10.1007/s12253-009-9238-x
PG 5
ER
PT J
AU Fang, Y
Zhao, L
Zang, M
Chen, S
Yan, F
Di, X
Duren, A
AF Fang, Yujiang
Zhao, Lei
Zang, Meifu
Chen, Songsen
Yan, Feng
Di, Xu
Duren, Alicia
TI A Dispensable Role for P450scc in the Overproduction of Aldosterone in Aldosterone-Producing Adenoma and Idiopathic Hyperaldosteronism in Patients with Primary Aldosteronism
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aldosteronism; Adrenocortical adenomas; Idiopathic hyepraldosteronism; P450scc
ID Aldosteronism; Adrenocortical adenomas; Idiopathic hyepraldosteronism; P450scc
AB Our previous study suggests that cytochrome P-450 carbon 17α-hydroxylase/17,20-lyase (P450c17α) correlated with the overproduction of aldosterone in aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) in patients with primary aldosteronism. To further investigate if cytochrome P-450 cholesterol side-chain cleavage enzyme (P450scc) contributes to the overproduction of aldosterone in APA and IHA and if its mRNA expression differs in APA and IHA in patients with primary aldosteronism, we studied the expression of P450scc mRNA in APA and idiopathic hyperplastic nodules. Total RNA was extracted from APA of eight patients diagnosed as APA, idiopathic hyperplastic nodules of four patients diagnosed as IHA, seven normal adrenal glands and one normal muscle tissue. P450scc mRNA was examined by Northern blot analysis. No significant difference in P450scc mRNA was found among normal adrenal gland, APA or idiopathic hyperplastic nodules (P>0.05). These results suggest that P450scc contributes little to the overproduction of aldosterone in APA and IHA and cannot be considered as a marker to differentiate between them in patients with primary aldosteronism.
C1 [Fang, Yujiang] University of Missouri, Department of Internal Medicine, 65211 Columbia, MO, USA.
[Zhao, Lei] Wannan Medical College, Department of Internal Medicine, 241004 Wuhu, China.
[Zang, Meifu] Pekin Union Medical College Hospital, Department of Urology, 100073 Beijing, China.
[Chen, Songsen] Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, 100073 Beijing, China.
[Yan, Feng] Wannan Medical College, Department of Internal Medicine, 241004 Wuhu, China.
[Di, Xu] Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, 100073 Beijing, China.
[Duren, Alicia] University of Missouri, Department of Internal Medicine, 65211 Columbia, MO, USA.
RP Fang, Y (reprint author), University of Missouri, Department of Internal Medicine, 65211 Columbia, USA.
EM fangy@health.missouri.edu
CR Gavras I, 2007, The incidentally discovered adrenal mass. N Engl J Med 356:2005–2006
Dluhy RG, Williams GH, 2004, Aldosterone–villain or bystander? N Engl JMed 351:8–10
Ganguly A, 1998, Primary aldosteronism. N Engl J Med 339:1828–1834
Fang Y, Zang M, Chen S, Di X, 2000, Expression of cytochrome P-450c17α-hydroxynase mRNA in adrenocortical adenomas and hyperplasia from patients with primary aldosteronism and its significance. Basic Med Sci Clin 20:30–33, Chinese
Chomczynski P, Sacchi N, 1987, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Chung B, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL, 1986, Human cholesterol side chain cleavage enzyme, P450scc: cDNAcloning, assignment of the gen to chromosone 15, and expression in the placenta. Proc Natl Acad Sci USA 83:8962– 8966
Morohashi L, Fujii-Kuriyama Y, Okada Y, Sogawa K, Hirose T, Inayama S, Omura T, 1984, Molecular cloning and nucleotide sequence of cDNA for mRNAof mitochondrial P450scc of bovine adrenal cortex. Proc Natl Acad Sci USA 81:4647
Morohashi K, Sogawa K, Omura T, Fujii-Luriyama Y, 1987, Gene structure of human cytochrome P450scc, cholesterol desmolase. J Biochem 101:879–887
Sparkea RS, Klisak I, Miller WL, 1991, Regional mapping of grnes encoding hyman steroidogenic enzymes: P450scc to 15q24- q25; and P450c17 to 10q24-q25. DNA Cell Biol 10:359–365
Ogo A, Haji M, Ohashi M, Nawata H, 1991, Expression of adrenocortical adenomas from patients with primary aldosteronism. Mol Cell Endocrinol 76:7–12
Shibata H, Suzuki H, Ogishima T, Ishimura Y, Saruta T, 1993, Significance of steroidogenic enzymes in the pathogenesis of adrenal tumour. Acta Endocrinol 128:235–242
Bassett MH, Mayhew B, Rehman K, White PC, Mantero F, Arnaldi G, Stewart PM, Bujalska I, Rainey WE, 2005, Expression profiles for steroidogenic enzymes in adrenocortical disease. J Clin Endocrinol Metab 90:5446–5455
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 589
EP 592
DI 10.1007/s12253-009-9237-y
PG 4
ER
PT J
AU Frohlich, G
Agoston, P
Lovey, J
Polgar, Cs
Major, T
AF Frohlich, Georgina
Agoston, Peter
Lovey, Jozsef
Polgar, Csaba
Major, Tibor
TI The Effect of Needle Number on the Quality of High-dose-rate Prostate Brachytherapy Implants
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dose-volume analysis; High-dose-rate; Prostate brachytherapy; Number of needles; Organs at risk; Treatment planning
ID Dose-volume analysis; High-dose-rate; Prostate brachytherapy; Number of needles; Organs at risk; Treatment planning
AB The aim of this study is to evaluate the effect of the number of needles on the quality of dose distributions in high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity and dose to organs at risk. Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms. The plans were divided into three groups according to the number of implanted needles: <15: LNG (low number group), 15–17: MNG (medium number group) and >17: HNG (high number group). Treatment planning was based on transrectal ultrasound imaging. Dose-volume parameters for target (V90, V100, V150, V200, D90, Dmin) and quality indices (DNR, DHI, CI, COIN) were calculated. Maximal dose in reference points and high dose volumes were determined for rectum and urethra. Nonparametric analysis of variance and correlation was used with regard to needle numbers. Between the groups differences were found only in the following parameters: Vp was larger when more needles were used with the values of 22.8 cm3, 28.0 cm3 and 30.9 cm3 for the three groups, and more needles were used when the central cross-section of the prostate was larger. V200 in MNG was lower than in LNG (12%, 14%). Dose to rectum was higher in MNG than in LNG (D2: 51%, 47%). Doses to the urethra were higher in HNG than in MNG (D1: 142%, 137%, and D0.1: 128%, 125%). There was no significant difference in other parameters. Different number of needles results significant differences in treatment plans. However, the optimal needle number depends on not only the size of the prostate, but also the individual anatomy of the patient. Based on our results, in most cases the use of 15–17 needles seems to provide a dosimetrically acceptable treatment plan in HDR prostate implants.
C1 [Frohlich, Georgina] Semmelweis University, School of PhD Studies, Ulloi ut 26, 1085 Budapest, Hungary.
[Agoston, Peter] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Lovey, Jozsef] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Major, Tibor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
RP Frohlich, G (reprint author), Semmelweis University, School of PhD Studies, 1085 Budapest, Hungary.
EM gfrohlich@oncol.hu
CR Akimoto T, Ito K, Saitoh JI et al, 2005, Acute genitourinary toxicity after high-dose-rate, HDR, brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity. Int J Radiat Oncol Biol Phys 63:463–471
Akimoto T, Katoh H, Noda SE et al, 2005, Acute genitourinary toxicity after high-dose-rate, HDR, brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity. Int J Radiat Oncol Biol Phys 63:472–478
Demanes DJ, Rodriguez RR, Altieri GA, 2000, High dose rate prostate brachytherapy: the California Endocurietherapy, CET, Method. Radiother Oncol 57:289–296
Demanes DJ, Rodriguez RR, Schour LD et al, 2005, High-doserate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California Endocurietherapy’s 10-year results. Int J Radiat Oncol Biol Phys 61:1306–1316
Hsu ICJ, Cabrera AR, Weinberg V et al, 2005, Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer. Brachytherapy 4:202–206
Jo J, Hiratsuka J, Fujii T et al, 2004, High-dose-rate Iridium-192 afterloading therapy combined with external beam radiotherapy for T1c-T3bN0M0 prostate cancer. Urology 64:556–560
Kovacs G, Melchert C, Sommerauer M et al, 2007, Intensity modulated high-dose-rate brachytherapy boost complementary to external beam radiation for intermediate- and high-risk localized prostate cancer patients—How we do it in Lubeck/Germany. Brachytherapy 6:142–148
Mate TP, Gottesman JE, Hatton J et al, 1998, High-dose-rate afterloading 192-Iridium prostate brachytherapy: feasibility report. Int J Radiat Oncol Biol Phys 41:525–533
Martin T, Hey-Koch S, Strassmann G et al, 2000, 3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Strahlenther Onkol 176:361–367
Pinkawa M, Fischedick K, Treusacher P et al, 2006, Dose-volume impact in high-dose-rate Iridium-192 brachytherapy as a boost to external beam radiotherapy for localized prostate cancer—a phase II study. Radiother Oncol 78:41–46
Vargas CE, Ghilezan M, Hollander M et al, 2005, A new model using number of needles and androgen deprivation to predict chronic urinary toxicity for high or low dose rate prostate brachytherapy. J Urol 174:882–887
Charra-Brunaud C, Hsu ICJ, Weinberg V et al, 2003, Analysis of interaction between number of implant catheters and dose-volume histograms in prostate high-dose-rate brachytherapy using a computer model. Int J Radiat Oncol Biol Phys 56:586–591
D’Amico AV, Whittington R, Malkowicz B et al, 1998, Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969–974
Baltas D, Kolotas C, Geramani K et al, 1998, A conformal index, COIN, to evaluate implant quality and dose specification in brachytherapy. Int J Radiat Oncol Biol Phys 40:515–524
Hoskin PJ, 2000, High-dose-rate brachytherapy boost treatment in radical radiotherapy for prostate cancer. Radiother Oncol 57:285– 288
Morton GC, 2005, The emerging role of high-dose-rate brachytherapy for prostate cancer. Clin Oncol 17:219–227
Sathya JR, Davis IR, Julian JA et al, 2005, Randomized trial comparing Iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 23:1192– 1199
Stromberg J, Martinez A, Gonzalez J et al, 1995, Ultrasoundguided high-dose-rate conformal brachytherapy boost in prostate cancer: treatment description and preliminary results of a phase I/II clinical trial. Int J Radiat Oncol Biol Phys 33:161–171
Martinez AA, Pataki I, Edmundson G et al, 2001, Phase II prospective study of the use of conformal highdose-rate brachytherapy as monotherapy for the treatment of favourable stage prostate cancer: a feasibility report. Int J Radiat Oncol Biol Phys 49:61–69
Yoshioka Y, Nose T, Yoshida K et al, 2003, High-dose-rate brachytherapy as monotherapy for localized prostate cancer: a retrospective analysis with special focus on tolerance and chronic toxicity. Int J Radiat Oncol Biol Phys 56:213–220
Edmundson GK, Rizzo NR, Teahan M et al, 1993, Concurrent treatment planning for outpatient high-dose-rate prostate template implants. Int J Radiat Oncol Biol Phys 27:1215–1223
Jacob D, Raben A, Sarkar A et al, 2008, Anatomy-based inverse planning simulated annealing optimization in high-dose-rate prostate brachytherapy: significant dosimetric advantage over other optimization techniques. Int J Radiat Oncol Biol Phys 72:820–827
Kolkman-Deurloo IKK, Deleye XGJ, Jansen PP et al, 2004, Anatomy based inverse planning in HDR prostate brachytherapy. Radiother Oncol 73:73–77
Nickers P, Lenaerts E, Thissen B et al, 2005, Does inverse planning applied to Iridium192 high dose rate prostate brachytherapy improve the optimization of the dose afforded by the Paris system? Radiother Oncol 74:131–136
Yoshioka Y, Nishimura T, Kamata M et al, 2005, Evaluation of anatomy-based dwell position and inverse optimization in highdose-rate brachytherapy of prostate cancer: a dosimetric comparison to a conventional cylindrical dwell position, geometric optimization, and dose-point optimization. Radiother Oncol 75: 311–317
Ash D, Flynn A, Battermann J et al, 2000, ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 57:315–321
Nag S, Bice W, Dewyngaert K et al, 2000, The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis. Int J Radiat Oncol Biol Phys 46:221–230
Kovacs G, Potter R, Loch T et al, 2005, GEC/ESTRO-EAU recommendations on temporary brachytherapy using stepping sources for localised prostate cancer. Radiother Oncol 74:37–148
Edmundson GK, Yan D, Martinez AA, 1995, Intraoperative optimization of needle placement and dwell times for conformal prostate brachytherapy. Int J Radiat Oncol Biol Phys 33:1257– 1263
Khoo VS, 2005, Radiotherapeutic techniques for prostate cancer, dose escalation and brachytherapy. Clin Oncol 17:560–571
Lakosi F, Antal G, Vandulek C et al, 2009, Technical feasibility of transperineal MR-guided prostate interventions in a low-field open MRI unit: canine study. Pathol Oncol Res 15(3):315–322
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 593
EP 599
DI 10.1007/s12253-010-9252-z
PG 7
ER
PT J
AU Dundr, P
Fischerova, D
Povysil, C
Berkova, A
Bauerova, L
Cibula, D
AF Dundr, Pavel
Fischerova, Daniela
Povysil, Ctibor
Berkova, Adela
Bauerova, Lenka
Cibula, David
TI Uterine Tumors with Neuroectodermal Differentiation. A Report of 4 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine tumors; PNET; Ewing sarcoma; EWSR1 gene; Neuroectodermal
ID Uterine tumors; PNET; Ewing sarcoma; EWSR1 gene; Neuroectodermal
AB We report four cases of uterine tumors with neuroectodermal differentiation. One tumor had neuroectodermal component only; in the three other tumors, the neuroectodermal component was admixed with another component, namely rhabdomyosarcoma (1 case), and endometrioid adenocarcinoma (2 cases). Histologically, the neuroectodermal component consisted of small to medium sized cells arranged in diffuse sheets. The tumor cells had round nuclei with stippled to coarsely granular chromatin, mostly with non-prominent nucleoli, and scant eosinophilic or amphophilic cytoplasm. Immunohistochemically, 4/4 tumors showed expression of vimentin, synaptophysin and CD56; 3/4 tumors were CD99 and NSE positive; 2/4 tumors showed focal expression of S-100 protein; and 1/4 tumors had focal dot-like cytoplasmic positivity for cytokeratin AE1/AE3. FLI-1 was negative in all cases. FISH examination was performed and none of the tumors showed rearrangement of EWSR1 gene. Uterine tumors with neuroectodermal differentiation are rare; to the best of our knowledge only 44 cases have been reported in the literature to date, referred to as Ewing sarcoma, peripheral PNET (pPNET), PNET (not otherwise specified) and uterine tumors with neuroendocrine differentiation.
C1 [Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Fischerova, Daniela] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and Gynecology, Apolinarska 18, 2 120 00 Prague, Czech Republic.
[Povysil, Ctibor] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Berkova, Adela] Charles University in Prague and General University Hospital in Prague, First Faculty of Medicine, 1st Department of Medicine—Department of Haematology, U nemocnice 2, 2 128 00 Prague, Czech Republic.
[Bauerova, Lenka] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 128 00 Prague, Czech Republic.
[Cibula, David] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and Gynecology, Apolinarska 18, 2 120 00 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 128 00 Prague, Czech Republic.
EM pdundr@seznam.cz
CR Wick MR, 2000, Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol 3:194–203
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Habib K, Finet JF, Plantier F et al, 1992, Rare lesion of the vulva. Arch Anat Cytol Pathol 40:158–159
Kawauchi S, Fukuda T, Miyamoto S et al, 1998, Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI- 1 chimeric mRNA. Am J Surg Pathol 22:1417–1422
Delattre O, Zucman J, Melot T et al, 1994, The Ewing family of tumors-a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331:294–299
Akbayir O, Gungorduk K, Rafioglu G et al, 2008, Primary primitive neuroectodermal tumor of the uterus: a case report. Arch Gynecol Obstet 277:345–348
Blattner JM, Gable P, Quigley MM, McHale MT, 2007, Primitive neuroectodermal tumor of the uterus. Gynecol Oncol 106:419–422
Celik H, Gurates B, Karaoglu A et al, 2009, Uterine primitive neuroectodermal tumor: a case report. Arch Gynecol Obstet 279:259– 261
Christensen B, Schmidt U, Schindler A, 1994, Primitive neuroectodermal tumor of the uterus—a monophasic differentiated mixed Mullerian tumor? Zentralbl Gynakol 116:577–580
Daya D, Lukka H, Clement PB, 1992, Primitive neuroectodermal tumors of the uterus: a report of four cases. Hum Pathol 23:1120– 1129
Euscher ED, Deavers MT, Lopez-Terrada D et al, 2008, Uterine tumors with neuroectodermal differentiation: a series of 17 cases and review of the literature. Am J Surg Pathol 32:219–228
Fraggetta F, Magro G, Vasquez E, 1997, Primitive neuroectodermal tumour of the uterus with focal cartilaginous differentiation. Histopathology 30:483–485
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Karseladze AI, Filipova NA, Navarro S, Llombart-Bosch A, 2001, Primitive neuroectodermal tumor of the uterus. A case report. J Reprod Med 46:845–848
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Molyneux AJ, Deen S, Sundaresan V, 1992, Primitive neuroectodermal tumour of the uterus. Histopathology 21:584–585
Ng SB, Sittampalam K, Chuah KL, 2002, Primitive neuroectodermal tumours of the uterus: a case report with cytological correlation and review of the literature. Pathology 34:455–461
Odunsi K, Olatinwo M, Collins Y et al, 2004, Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature. Gynecol Oncol 92:689–696
Park JY, Lee S, Kang HJ, Kim HS, Park SY, 2007, Primary Ewing’s sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review. Gynecol Oncol 106: 427–432
Peres E, Mattoo TK, Poulik J, Warrier I, 2005, Primitive neuroectodermal tumor, PNET, of the uterus in a renal allograft patient: a case report. Pediatr Blood Cancer 44:283–285
Quddus MR, Rashid L, Sung J et al, 2009, Ewing´s sarcoma / Peripheral primitive neuroectodermal tumor, ES/PNET, differentiation in endometrial serous carcinomas. Reprod Sci 16:591– 595
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Sinkre P, Albores-Saavedra J, Miller DS, Copeland LJ, Hameed A, 2000, Endometrial endometrioid carcinomas associated with Ewing sarcoma/peripheral primitive neuroectodermal tumor. Int J Gynecol Pathol 19:127–132
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 601
EP 608
DI 10.1007/s12253-010-9249-7
PG 8
ER
PT J
AU Jain, KR
Mehta, R
Badve, S
AF Jain, K Rohit
Mehta, Rutika
Badve, Sunil
TI Conjunctival Squamous Cell Carcinoma Due to Ocular Prostheses: A Case Report and Review of Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Conjunctiva; Squamous cell carcinoma; Prostheses
ID Conjunctiva; Squamous cell carcinoma; Prostheses
AB Conjunctival squamous cell carcinoma (SCC) is a rare finding in everyday clinical practice, but is the most common malignancy of the ocular surface. The incidence of this malignancy in the United States is 0.03 per 100,000 persons. It is one extreme of a spectrum of lesions encompassed in ocular surface squamous neoplasia which range from dysplasia to carcinoma in situ to invasive SCC. Exposure to ultraviolet radiation B (UVB), human papilloma virus (HPV), and human immunodeficiency virus (HIV) infection of eroded ocular surface are important risk factors predisposing to the development of this malignancy. Herein we report a case of SCC arising in chronic conjunctival irritation due to prolonged prosthetic use following enucleation for traumatic eye injury.
C1 [Jain, K Rohit] Indiana University, Department of Pathology, 350 W 11th Street, CPL 4010, 46202 Indianapolis, IN, USA.
[Mehta, Rutika] Indiana University, Department of Pathology, 350 W 11th Street, CPL 4010, 46202 Indianapolis, IN, USA.
[Badve, Sunil] Indiana University, Department of Pathology, 350 W 11th Street, CPL 4010, 46202 Indianapolis, IN, USA.
RP Badve, S (reprint author), Indiana University, Department of Pathology, 46202 Indianapolis, USA.
EM sbadve@iupui.edu
CR McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD, 2002, Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol 86(2):168–173
Nguyen J, Ivan D, Esmaeli B, 2008, Conjunctival squamous cell carcinoma in the anophthalmic socket. Ophthal Plast Reconstr Surg 24(2):98–101
Newton R, Ziegler J, Ateenyi-Agaba C, Bousarghin L, Casabonne D, Beral V et al, 2002, The epidemiology of conjunctival squamous cell carcinoma in Uganda. Br J Cancer 87(3):301–308
Shields JA, Shields CL, 2007, Conjunctival invasive squamous cell carcinoma. In: Shields JA, Shields CL, eds, Eyelid, conjunctival, and orbital tumors: an atlas and textbook, 2nd ed. Lippincott Williams & Wilkins, New York, pp 292–306
Whittaker KW, Trivedi D, Bridger J, Sandramouli S, 2002, Ocular surface squamous neoplasia: report of an unusual case and review of the literature. Orbit, Amsterdam, Netherlands, 21, 3):209–215
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Chang WJ, Tse DT, Rosa RH, Huang A, Johnson TE, Schiffman J, 2005, Conjunctival cytology features of giant papillary conjunctivitis associated with ocular prostheses. Ophthal Plast Reconstr Surg 21(1):39–45
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Tunc M, Char DH, Crawford B, Miller T, 1999, Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases. Br J Ophthalmol 83(1):98–103
Tuppurainen K, Raninen A, Kosunen O, Kankkunen JP, Kellokoski J, Syrjanen S et al, 1992, Squamous cell carcinoma of the conjunctiva. Failure to demonstrate HPV DNA by in situ hybridization and polymerase chain reaction. Acta Ophthalmol 70(2):248– 254
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Chaudhry TA, Memon M, Ahmad K, 2006, Use of artificial eye and conjunctival squamous cell carcinoma. J Postgrad Med 52(3):234–235
Endo T, Hata J, Togashi S, Yanagibayashi S, Nakayama Y, 2006, Conjunctival squamous cell carcinoma of the orbit 40 years after enucleation. Ophthal Plast Reconstr Surg 22(4):299–301
Campanella PC, Goldberg SH, Erlichman K, Abendroth C, 1998, Squamous cell tumors and ocular prostheses. Ophthal Plast Reconstr Surg 14(1):45–49
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 609
EP 612
DI 10.1007/s12253-010-9251-0
PG 4
ER
PT J
AU Terada, T
AF Terada, Tadashi
TI Minute Myopericytoma of the Neck: A Case Report with Literature Review and Differential Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Skin; Myopericytoma; Perivascular myoid cells; Histopathology; Immunohistochemistry
ID Skin; Myopericytoma; Perivascular myoid cells; Histopathology; Immunohistochemistry
AB Reports of cutaneous myopericytoma (MPC) are very rare. The author herein reports a case of minute MPC of the neck. A 56-year-old woman noticed a painful small tumor in the neck, and consulted to our hospital. Dermatologists’s diagnosis is a hyperplastic lymph node. Excision of the tumor was performed. Grossly, the tumor was a sold white tumor measuring 3×3×3 mm. Microscopically, it consisted of many vascular channels and perivascular cell proliferation encased by a fibrous capsule. The vascular proliferation showed a hemangiopericytoma (HPC)-like pattren such as staghorn-like vessels. Fibrosis was not present. The HPC-like cells had vesicular nuclei and polygonal cytoplasm. No atypia is recognized. The HPC-like cells focally showed vague nodular proliferation around the vessels. Immunohistocheically, the tumor cells were negative for cytokeratin, and positive for vimentin. The vasculatures were positive for factor VIII-related antigen, CD34, and CD31. The HPC-like tumor cells were positive for α-smooth muscle actin and h-caldesmon, but negative for desmin, S100 protein, melanosome, bcl-2, CD99, and KIT. The Ki-67 labeling was 8% and p53 was negative. The pathologic diagnosis was MPC of the neck skin. The patient is now alive without recurrence 4 years after the excision. A review of the literature revealed 73 cases of MPC from 6 papers. MPC is male predominance, and the patients ages ranges from 13 to 87 years with the median of 47 years. The most common location was lower extremities followed in order by upper extremities, head and neck, and trunk. One MPC occurred within the vasculature, and 3 cases of MPC developed in the scar or trauma lesions. The prognosis after excision is good, but a very minority showed local recurrence. A differential diagnosis was also made.
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231, Shimizu-Ku, 424-8636 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 424-8636 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
CR Middeleton LP, Duray PH, Merino MJ, 1998, The histological spectrum of hemangiopericytoma: application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis. Hum Pathol 29:636–640
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Menzel T, Del Tos AP, Sapi Z, Kutzner H, 2006, Myopericytoma of the skin and soft tissue: clinicopathologic and immunohistochemical study of 54 cases. Am J Surg Pathol 30:104–113
Dray MS, McCarthy SW, Palmer AA, Bonar SF, Stalley PD, Marjoniemi V, Millar E, Scolyer RA, 2006, Myoipericytoma: a unifying term for a spectrum of tumours that show overlapping features with myofibroma. A review of 14 cases. J Clin Pathol 59:67–73
Folpes AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW, 2005, Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 29:1558–1575
Liegl B, Hornick JL, Fletcher CD, 2008, Primary cutaneous PEComa: distinctive clear cell lesions of skin. Am J Surg Pathol 32:608–614
Miettinen M, Paal E, Lasota J, Sobin JH, 2002, Gastrointestinal glomus tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 32 cases. Am J Surg Pathol 26:301– 311
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Lin IH, Kuo FY, Su CY, Lin HC, 2006, Sinonasal-type hemangiopericytoma of the sphenoid sinus. Otolaryngol Head Neck Surg 135:977–979
Rajaram V, Brat DJ, Perry A, 2004, Anaplastic meningioma versus meningeal hemangiopericytoma: immunohistochemical and genetic markers. Hum Pathol 35:1413–1418
Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y, 2002, Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746
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Alawi F, Stratton D, Freedman PD, 2001, Solitary fibrous tumor of the oral soft tissue: a clinicopathological and immunohistochemical study of 16 cases. Am J Surg Pathol 35:900–910
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Terada T, 2009, Primary extragastrointestinal stromal tumors of the transverse mesocolon without c-kit mutations but with PDGFRA mutations. Med Oncol 26:233–237
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Michal M, Fanburg-Smith JC, Lasota J, Fetsch JF, Lichky J, Miettinen M, 2006, Minute synovial sarcoma of the hands and feet: a clinicopathologic study of 21 tumors less than 1 cm. Am J Surg Pathol 30:721–726
McMenamin ME, Fletcher CD, 2002, Malignant myopericytoma: expanding the spectrum of tumours with myopericytic differentiation. Histopathology 41:450–460
Scott RS, Blank KL, Proffer LH, Kraus EW, Heim-Hall J, 2006, Perivascular myoma of myopericytoma and myofibromatosis-type arising in a chronic scar. J Cutan Pathol 33:231–235
Laga AC, Tajirian AL, Islam MN, Bhattachayya I, Cohen DM, Plamondon CJ, Robinson-Bostom L, 2008, Myopericytoma: report of two cases associated with trauma. J Cutan Pathol 35:866–870
McMenamin ME, Calonje E, 2002, Intravascular myopericytoma. J Cutan Pathol 29:557–561
Mimami Y, Shiomi T, Manaba T, 2002, Perivascular myoma: case report and immunohistochemical and ultrastructural studies. Pathol Int 52:69–74
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2010
VL 16
IS 4
BP 613
EP 616
DI 10.1007/s12253-010-9253-y
PG 4
ER
PT J
AU Wang, Y
Sun, W
Guan, Ch
Yu, H
Pan, MZ
AF Wang, Yan
Sun, Weijia
Guan, Chao
Yu, He
Pan, M Z
TI Distribution of Basement Membrane in Supraglottic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Supraglottic squamous cell carcinoma; Basement membrane; Type IV collagen; Cervical lymph node metastasis
ID Supraglottic squamous cell carcinoma; Basement membrane; Type IV collagen; Cervical lymph node metastasis
AB The object of this study was to assess the distribution of basement membrane in supraglottic squamous cell carcinomas. Expression of type IV collagen was detected by immunohistochemistry in resected supraglottic squamous cell carcinomas, and the correlation was examined between expression of type IV collagen and clinicopathological factors and cervical lymph node metastasis of supraglottic squamous cell carcinomas patients. An intact, continuous basement membrane was found in 17 cases (42.5%), while partial or widespread loss of the basement membrane was detected in the other 23 cases (57.5%). Heavily defective basement membrane was much more frequently observed in cases with poor histological differentiation (P<0.05). Cases with BM destruction were more likely to be accompanied by cervical lymph node metastasis (P<0.05). These data suggest that assessing the distribution pattern of basement membrane may be helpful in evaluating the malignancy grading of supraglottic squamous cell carcinomas and the potential occurrence of cervical lymph node metastasis.
C1 [Wang, Yan] China Medical University, The 1st Affiliated Hospital, Department of Otolaryngology, 110001 Shenyang, China.
[Sun, Weijia] China Medical University, The 4th Affiliated Hospital, Department of Surgery, 110001 Shenyang, China.
[Guan, Chao] China Medical University, The 1st Affiliated Hospital, Laryngal Cancer Research Institution, 110001 Shenyang, China.
[Yu, He] China Medical University, The 1st Affiliated Hospital, Department of Otolaryngology, 110001 Shenyang, China.
[Pan, M Z] China Medical University, The 1st Affiliated Hospital, Department of Otolaryngology, 110001 Shenyang, China.
RP Wang, Y (reprint author), China Medical University, The 1st Affiliated Hospital, Department of Otolaryngology, 110001 Shenyang, China.
EM wangyan@mail.cmu.edu.cn
CR Brown PD, Levy AT, Margulies IM, Liotta LA, Stetler-Stevenson WG, 1990, Independent distribution pattern and celluler processing of the 72 KD type IV collagenase and interstital collagenase in human tumorgenic cell lines. Cancer Res 50:6184–6191
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 1
EP 5
DI 10.1007/s12253-010-9250-1
PG 5
ER
PT J
AU Mojtahedi, Z
Khademi, B
Hashemi, BS
Abtahi, MBS
Ghasemi, AM
Fattahi, JM
Ghaderi, A
AF Mojtahedi, Zahra
Khademi, Bijan
Hashemi, Basir Seyed
Abtahi, Mohammad Bagher Seyed
Ghasemi, Ali Mohammad
Fattahi, Javad Mohammad
Ghaderi, Abbas
TI Serum Interleukine-6 Concentration, But Not Interleukine-18, is Associated with Head and Neck Squamous Cell Carcinoma Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cytokine; Head and neck neoplasms; Interleukin-18; Interleukin-6; SCC
ID Cytokine; Head and neck neoplasms; Interleukin-18; Interleukin-6; SCC
AB Inflammation has been linked to various steps in tumorigenesis. Interleukin (IL)-6 and IL-18 are two inflammatory cytokines whose serum concentrations are elevated in several types of cancer, including head and neck squamous cell carcinoma (HNSCC) in some studies. This study was designed to analyze the serum concentrations of these cytokines in Iranian HNSCC patients. Serum IL-6 and IL-18 concentrations were assayed by ELISA commercial kits in 65 untreated patients and 20 healthy volunteers. Serum IL-6 concentration was significantly increased in patients compared to healthy individuals (p<0.000). IL-6 concentration increased as the tumor stage progressed, and a significant difference appeared between stage IV vs. stage I/II/III (p=0.03) disease. Although serum IL-18 concentration was higher in patients than in healthy individuals, the difference was not statistically significant (p=0.06). Moreover, there was no association between serum IL-18 concentration and tumor stage (p=0.47). A significant difference was observed in serum IL-18 concentration according to the gender with higher IL-18 concentration in male patients (p=0.01). In conclusion, serum concentration of IL-6 might correlate with the stage of tumor progression in Iranian HNSCC patients. Further studies with larger numbers of patients are required to exclude the possible minor correlation of serum IL-18 concentration with tumor stage.
C1 [Mojtahedi, Zahra] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Khademi, Bijan] Shiraz University of Medical Sciences, Khalili hospital, Department of ENTShiraz, Iran.
[Hashemi, Basir Seyed] Shiraz University of Medical Sciences, Khalili hospital, Department of ENTShiraz, Iran.
[Abtahi, Mohammad Bagher Seyed] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghasemi, Ali Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Fattahi, Javad Mohammad] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghaderi, Abbas] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
RP Ghaderi, A (reprint author), Shiraz University of Medical Sciences, Institute for Cancer Research, Shiraz, Iran.
EM ghaderia@sums.ac.ir
CR Hardisson D, 2003, Molecular pathogenesis of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 260:502– 508
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Jebreel A, Mistry D, Loke D et al, 2007, Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer. J Laryngol Otol 121:246–252
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 7
EP 10
DI 10.1007/s12253-010-9261-y
PG 4
ER
PT J
AU Valcz, G
Krenacs, T
Sipos, F
Leiszter, K
Toth, K
Balogh, Zs
Csizmadia, A
Muzes, Gy
Molnar, B
Tulassay, Zs
AF Valcz, Gabor
Krenacs, Tibor
Sipos, Ferenc
Leiszter, Katalin
Toth, Kinga
Balogh, Zsofia
Csizmadia, Annamaria
Muzes, Gyorgyi
Molnar, Bela
Tulassay, Zsolt
TI The Role of the Bone Marrow Derived Mesenchymal Stem Cells in Colonic Epithelial Regeneration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mesenchymal stem cells; Mucosal regeneration; Mesenchymal-epithelial transition; Isolated lymphoid aggregates
ID Mesenchymal stem cells; Mucosal regeneration; Mesenchymal-epithelial transition; Isolated lymphoid aggregates
AB Bone marrow derived mesenchymal stem cells (BM-MSCs) take part in the colonic mucosal regeneration. They are multipotent cells, which can be identified with both negative (i.e. CD13, CD 14, CD45, c-Kit, major histocompatibility complex /MHC class I and II) and positive (i.e. CD54 (ICAM1), CD133, CD146 (MCAM), CD166, Flk-1, Sca-1, Thy-1, stage-specific antigen I /SSEAI and Musashi-1, HLA class I) markers. These cells can repopulate the gastrointestinal mucosa as they may differentiate into stromal- (i.e. myofi-broblast) or epithelial-like (Paneth-, epithel-, goblet or enteroendocrin) cells without proliferation. During the mesenchymal to epithelial transition (MET) stem cells enter the epithelial layer and take up epithelial cell-like properties. Rarely BM-MSCs may retain their stem cell characteristics and are capable of producing progeny. The isolated lymphoid aggregates may serve as a platform from where BM-MSCs migrate to the nearby crypts as mediated by several chemoattractant proteins, which are expressed in injured tissue. The number of BM-MSCs is influenced by the degree of inflammation. In this review we summarize the current information about the role of BM-MSCs in the repair progress of injured colonic epithelium and their potential clinical applications.
C1 [Valcz, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Leiszter, Katalin] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Balogh, Zsofia] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csizmadia, Annamaria] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Muzes, Gyorgyi] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
RP Valcz, G (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM valczg@yahoo.com
CR Grove JE, Bruscia E, Krause DS, 2004, Plasticity of bone marrow-derived stem cells. Stem Cells 22:487–500
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 11
EP 16
DI 10.1007/s12253-010-9262-x
PG 6
ER
PT J
AU Kovacs,
Lakosi, F
Liposits, G
Toller, G
Hadjiev, J
Vandulek, Cs
Walter, N
Glavak, Cs
Antal, G
Horvath,
Repa, I
Bogner, P
AF Kovacs, Arpad
Lakosi, Ferenc
Liposits, Gabor
Toller, Gabor
Hadjiev, Janaki
Vandulek, Csaba
Walter, Norbert
Glavak, Csaba
Antal, Gergely
Horvath, Akos
Repa, Imre
Bogner, Peter
TI 3-D Conformal Photon Boost in the Treatment of Early Stage Breast Cancer: Four Year Follow Up Results
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Radiotherapy; 3-D conformal photon boost
ID Breast cancer; Radiotherapy; 3-D conformal photon boost
AB In the treatment of early stage breast cancer, breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard treatment. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study we demonstrate our 4 year experience with the 3-D conformal boost technique. Between January 2004 and June 2005, 77 early stage (Stage I–II) breast cancer patients were treated in our institute with whole breast irradiation (WBI, 50.4 Gy in 28 fractions) after breast conserving surgery. Following WBI, 3-D conformal photon boost was delivered (10–16 Gy in five to eight fractions) for all patients. The clinical outcome was retrospectively recorded in terms of survival and local control. The side effect profile (fibrosis, fat necrosis and cosmetic outcome) was also recorded and studied. In our patient group the mean follow up time was 46.8 months (median: 52, range: 17–71, SD: 14.4) The 4-year probability of local tumor control was 96% (crude rate: 74/77–96.1%), the 4-year probability of overall survival was 96% (crude rate: 74/77–96.1%) in this patient group. In case of the distant metastasis free survival the probability was 89, 5% (crude rate: 70/77–90, 1%). Probability of disease specific survival was 98% (crude rate: 76/77–98. 7%). Local relapse occurred in three cases (3.9%). In ten cases (12.9%) asymptomatic grade I–II breast fibrosis, in eight cases (10.4%) asymptomatic breast fat necrosis were registered. For 14 patients (18.2%) asymptomatic lung fibrosis was recorded on the control CT scans. In term of the relapse free survival, the close resection margin and the nodal positivity resulted in significant difference in favor of the clear resection margin group and the node negative group. In this study the 3-D conformal photon boost resulted in good local control and side effect profile. The presence of tumor bed clips resulted in significantly lower boost PTV volumes, but no correlation was found between the irradiated boost volume and the breast fibrosis. In the relapse free survival analysis, nodal negativity and clear margin status resulted in significantly better RFS.
C1 [Kovacs, Arpad] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Lakosi, Ferenc] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Liposits, Gabor] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Toller, Gabor] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Hadjiev, Janaki] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Vandulek, Csaba] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Walter, Norbert] University of Pecs, Faculty of Health Sciences, Vorosmarty u. 4., H-7621 Pecs, Hungary.
[Glavak, Csaba] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Antal, Gergely] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Horvath, Akos] University of DebrecenDebrecen, Hungary.
[Repa, Imre] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
[Bogner, Peter] Kaposi Mor Teaching Hospital, Guba S. u 40, 7400 Kaposvar, Hungary.
RP Kovacs, (reprint author), Kaposi Mor Teaching Hospital, 7400 Kaposvar, Hungary.
EM kovacs.arpad@sic.hu
CR Bartelink H, Horiot JC, Poortmans P et al, 2001, Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 345:1378–1387
Bates A, Swift C, Kwa W, Moravan V, Aquino-Parsons C, 2007, A computed tomography-based protocol vs conventional clinical mark-up for breast electron boost. Clin Oncol 19:349–355
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Kovacs A, Hadjiev J, Lakosi F et al, 2008, Comparison of photon with electron boost in treatment of early stage breast cancer. Pathol Oncol Res 14:193–197
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Poortmans P, Bartelink H, Horiot J-C, Struikmans H, Van den Bogaert W, Fourquet A, Jagerg J, Hoogenraadh W, Rodrigusa P, Rodenhuisi CW, Collette L, Pierartj M, On behalf of the EORTC Radiotherapy and Breast Cancer Groups, 2004, The influence of the boost technique on local control in breast-conserving treatment in the EORTC ‘boost versus no boost’ randomized trial. Radiother Oncol 72:25–33
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 17
EP 23
DI 10.1007/s12253-010-9264-8
PG 7
ER
PT J
AU Saucy, F
Bachmann, D
Peterman, O
Sordat, B
Sordat, I
Dorta, G
AF Saucy, Francois
Bachmann, Daniel
Peterman, Olivier
Sordat, Bernard
Sordat, Isabelle
Dorta, Gian
TI The Plasminogen System in Microdissected Colonic Mucosa Distant from an Isolated Adenoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urokinase-type plasminogen activators; Plasminogen activator inhibitors; Laser microdissection; Tubular adenoma; Colonic stroma; Colonic epithelium
ID Urokinase-type plasminogen activators; Plasminogen activator inhibitors; Laser microdissection; Tubular adenoma; Colonic stroma; Colonic epithelium
AB In the colon, the urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors, PAI-1 and PAI-2, are implicated in the transition from mucosa to adenoma and tumour progression. However, expression in the mucosa adjacent, or distant, to an adenoma has not yet been investigated. Three biopsies from mucosae adjacent (20 cm, ipsilateral) and distant (contralateral) to an isolated tubular adenoma were analysed in 14 patients and 8 controls. Laser microdissection isolated stromal and epithelial crypt components, and quantitative RT-PCR analyses of uPA, uPAR, PAI-1 and PAI-2 mRNA levels were performed. Among controls, no significant differences in the markers were noted. With left colon isolated tubular adenoma, uPA, uPAR, and PAI-2 mRNA levels were significantly increased in the adjacent mucosal stroma compared to epithelial crypt levels (p<0.05). In right colon adenoma, the mRNA levels of these 3 molecular markers were significantly increased only in the adjacent mucosal stromal samples (p<0.05). Isolated tubular adenoma in the colon increases significantly the mRNA levels of 3 proteolysis-associated molecular markers in the stromal, but not in the epithelial, components of adjacent mucosa. These results suggest the presence of regional and dynamic interactions in apparently non-involved mucosae.
C1 [Saucy, Francois] University Hospital Lausanne, Division of Gastroenterology and Hepatology, 1011 Lausanne, Switzerland.
[Bachmann, Daniel] University Hospital Lausanne, Division of Gastroenterology and Hepatology, 1011 Lausanne, Switzerland.
[Peterman, Olivier] Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland.
[Sordat, Bernard] Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland.
[Sordat, Isabelle] Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland.
[Dorta, Gian] University Hospital Lausanne, Division of Gastroenterology and Hepatology, 1011 Lausanne, Switzerland.
RP Saucy, F (reprint author), University Hospital Lausanne, Division of Gastroenterology and Hepatology, 1011 Lausanne, Switzerland.
EM francois.saucy@chuv.ch
CR Parkin DM, Bray F, Ferlay J, Pisani P, 2001, Estimating the world cancer burden: Globocan 2000. Int J Cancer 94(2):153–156
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Gregorieff A, Clevers H, 2005, Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev 19(8):877–890
Galon J, Fridman WH, Pages F, 2007, The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 67(5):1883–1886
van den Brink GR, Offerhaus GJ, 2007, The morphogenetic code and colon cancer development. Cancer Cell 11(2):109–117
Dano K, Behrendt N, Hoyer-Hansen G, Johnsen M, Lund LR, Ploug M et al, 2005, Plasminogen activation and cancer. Thromb Haemost 93(4):676–681
Mazzieri R, Blasi F, 2005, The urokinase receptor and the regulation of cell proliferation. Thromb Haemost 93(4):641–646
Yang L, Avila H, Wang H, Trevino J, Gallick GE, Kitadai Y et al, 2006, Plasticity in urokinase-type plasminogen activator receptor, uPAR, display in colon cancer yields metastable subpopulations oscillating in cell surface uPAR density–implications in tumor progression. Cancer Res 66(16):7957–7967
Czekay RP, Aertgeerts K, Curriden SA, Loskutoff DJ, 2003, Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol 160(5):781–791
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Sordat I, Chaubert P, Protiva P, Guillou L, Mazzucchelli L, Saraga E et al, 1997, In situ stromal expression of the urokinase/plasmin system correlates with epithelial dysplasia in colorectal adenomas. Am J Pathol 150(1):283–295
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Danjoux M, Guimbaud R, Al Saati T, Meggetto F, Carrere N, Portier G et al, 2006, Contribution of microdissection for the detection of microsatellite instability in colorectal cancer. Hum Pathol 37(3):361–368
Sabates-Bellver J, Van der Flier LG, de Palo M, Cattaneo E, Maake C, Rehrauer H et al, 2007, Transcriptome profile of human colorectal adenomas. Mol Cancer Res 5(12):1263– 1275
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Del Rosso M, Fibbi G, Pucci M, Margheri F, Serrati S, 2008, The plasminogen activation system in inflammation. Front Biosci 13:4667–4686
Sier CF, Verspaget HW, Griffioen G, Verheijen JH, Quax PH, Dooijewaard G et al, 1991, Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis. Gastroenterology 101, 6):1522–1528
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Issa JP, 2008, Colon cancer: it's CIN or CIMP. Clin Cancer Res 14(19):5939–5940
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 25
EP 31
DI 10.1007/s12253-010-9268-4
PG 7
ER
PT J
AU Lu, S
Tian, J
Lv, Z
Wang, H
Bai, X
Liu, W
Li, J
Xu, W
AF Lu, Sumei
Tian, Jiajun
Lv, Zhenghua
Wang, Haibo
Bai, Xiaohui
Liu, Wenwen
Li, Jianfeng
Xu, Wei
TI The Probable Role of Tumor Stem Cells for Lymph Node Metastasis in Supraglottic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD133; CD44; Lymph node metastasis; Supraglottic carcinoma; Tumor stem cell
ID CD133; CD44; Lymph node metastasis; Supraglottic carcinoma; Tumor stem cell
AB Tumor stem cells (TSC), which are considered as likely candidates for the origin of cancer, are deduced to be responsible for tumor metastasis theoretically. We therefore investigated whether TSC were associated with lymph node metastasis in supraglottic carcinoma. Immunohistochemistry was performed for CD44, CD133, and LYVE-1 to detect TSC and lymphatic vessel density (LVD) in 66 primary supraglottic carcinoma tissue samples from 30 patients with lymph node metastasis (N+) and 36 patients without (N0). Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of CD44 and CD133 at mRNA and protein levels in N+ and N0 primary tumors. The LVD was 22.4±10.26 in 30N+ and 6.8±4.09 in 36N0 samples subjected to immunohistochemistry, which was associated with their clinical nodal stages. There were 43.33% CD44-positive and 93.33% CD133-positive samples in 30N+, and 13.89% CD44-positive and 44.44% CD133-positive samples in 36N0 (P<0.05). However, in each positive slide, there were only 5∼10% CD44-positive cells, but 70∼85% CD133-possitive cells. The expressions of CD44 and CD133 of N+ obtained through RT-PCR and Western blot were significantly higher than those of N0. These results suggest that TSC identified through CD44-positive cells in N+ were significantly higher than those in N0, indicating that TSC may be responsible for lymph node metastasis. CD133, whose expression is not restricted to TSC, may be unspecific for TSC identification in hypostatic supraglottic carcinoma.
C1 [Lu, Sumei] Provincial Hospital affiliated to Shandong University, Institute of Eye and ENT, 250021 Jinan, China.
[Tian, Jiajun] Provincial Hospital affiliated to Shandong University, Department of Otolaryngology-Head and Neck Surgery, 250021 Jinan, China.
[Lv, Zhenghua] Provincial Hospital affiliated to Shandong University, Department of Otolaryngology-Head and Neck Surgery, 250021 Jinan, China.
[Wang, Haibo] Provincial Hospital affiliated to Shandong University, Institute of Eye and ENT, 250021 Jinan, China.
[Bai, Xiaohui] Provincial Hospital affiliated to Shandong University, Institute of Eye and ENT, 250021 Jinan, China.
[Liu, Wenwen] Provincial Hospital affiliated to Shandong University, Institute of Eye and ENT, 250021 Jinan, China.
[Li, Jianfeng] Provincial Hospital affiliated to Shandong University, Institute of Eye and ENT, 250021 Jinan, China.
[Xu, Wei] Provincial Hospital affiliated to Shandong University, Department of Otolaryngology-Head and Neck Surgery, 250021 Jinan, China.
RP Xu, W (reprint author), Provincial Hospital affiliated to Shandong University, Department of Otolaryngology-Head and Neck Surgery, 250021 Jinan, China.
EM xwhns@yahoo.com.cn
CR Kyzas PA, Geleff S, Batistatou A et al, 2005, Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J Pathol 206(2):170–7
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 33
EP 38
DI 10.1007/s12253-010-9271-9
PG 6
ER
PT J
AU Hadarits, F
Kisfali, P
Mohas, M
Maasz, A
Sumegi, K
Szabo, M
Hetyesy, K
Valasek, A
Janicsek, I
Wittmann, I
Melegh, B
AF Hadarits, Ferenc
Kisfali, Peter
Mohas, Marton
Maasz, Anita
Sumegi, Katalin
Szabo, Melinda
Hetyesy, Katalin
Valasek, Andrea
Janicsek, Ingrid
Wittmann, Istvan
Melegh, Bela
TI Stepwise Positive Association Between APOA5 Minor Allele Frequencies and Increasing Plasma Triglyceride Quartiles in Random Patients with Hypertriglyceridemia of Unclarified Origin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ApoA5; Hypertriglyceridemia; T-1131C; IVS3+G476A; T1259C; C56G; PCR-RFLP
ID ApoA5; Hypertriglyceridemia; T-1131C; IVS3+G476A; T1259C; C56G; PCR-RFLP
AB Apolipoprotein A5 (ApoA5) gene and its protein product play a central role in the complex regulation of circulating triglyceride levels in humans. Naturally occurring variants of the apolipoprotein A5 gene have been associated with increased triglyceride levels and have been found to confer risk for cardiovascular diseases. In our study, four polymorphisms, the T-1131C, IVS3+G476A, T1259C, and C56G alleles of APOA5 were analyzed in a total of 436 patients by polymerase chain reaction—restriction fragment length polymorphism methods. The randomly selected patients were classified into four quartile (q) groups based on triglyceride levels (q1: TG<1.31 mmol/l; q2: 1.31–2.90 mmol/l; q3: 2.91–4.85 mmol/l; q4: TG>4.85 mmol/l). We observed significant stepwise increasing association between the four APOA5 minor allele carrier frequencies and plasma triglyceride quartiles: -1131C (q1: 4.44%; q2: 8.95%; q3: 12.9%; q4: 20.6%), IVS3+476A (q1: 4.44%; q2: 5.79%; q3: 11.1%; q4: 19.7%), 1259C (q1: 4.44%; q2: 6.84%; q3: 11.1%; q4: 20.6%) and 56G (q1: 5.64%; q2: 6.31%; q3: 11.16%; q4: 11.9%). The serum total cholesterol and high density lipoprotein-cholesterol levels also showed allele-dependent differences in the quartiles. The findings presented here revealed a special arrangement of APOA5 minor alleles in patients with different serum triglyceride ranges in Hungarians.
C1 [Hadarits, Ferenc] Markusovszky County Hospital, Central LaboratorySzombathely, Hungary.
[Kisfali, Peter] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Mohas, Marton] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Sumegi, Katalin] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Szabo, Melinda] Robert Koch Hospital, Department of PulmonologyEdeleny, Hungary.
[Hetyesy, Katalin] Aladar Petz County Hospital, Central LaboratoryGyor, Hungary.
[Valasek, Andrea] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Janicsek, Ingrid] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Wittmann, Istvan] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, Pecs, Hungary.
EM bela.melegh@aok.pte.hu
CR Charlton M, 2009, Obesity, hyperlipidemia, and metabolic syndrome. Liver Transpl 15:S83–S89
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Ewald N, Hardt PD, Kloer HU, 2009, Severe hypertriglyceridemia and pancreatitis: presentation and management. Curr Opin Lipidol
Hopkins PN, Heiss G, Ellison RC et al, 2003, Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 108:519–523
St-Pierre J, Lemieux I, Vohl MC et al, 2002, Contribution of abdominal obesity and hypertriglyceridemia to impaired fasting glucose and coronary artery disease. Am J Cardiol 90:15–18
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Baum L, Tomlinson B, Thomas GN, 2003, APOA5-1131T>C polymorphism is associated with triglyceride levels in Chinese men. Clin Genet 63:377–379
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Wang J, BanMR, Kennedy BA et al, 2008, APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia. Nat Clin Pract Cardiovasc Med 5:730–737
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 39
EP 44
DI 10.1007/s12253-010-9273-7
PG 6
ER
PT J
AU Liu, B
Zhang, Y
Liao, M
Deng, Z
Gong, L
Jiang, J
Lynn, L
Wu, K
Miao, X
AF Liu, Bo
Zhang, Yangde
Liao, Mingmei
Deng, Zhansheng
Gong, Liansheng
Jiang, Jiarui
Lynn, Ling
Wu, Kai
Miao, Xiongying
TI Clinicopathologic and Prognostic Significance of CD24 in Gallbladder Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder carcinoma; CD24; Clinicopathology; Prognosis
ID Gallbladder carcinoma; CD24; Clinicopathology; Prognosis
AB CD24, a small cell surface protein, has emerged as a novel oncogene and prognostic factor for poor outcomes in many human cancers. However, the association of CD24 expression pattern in gallbladder carcinoma with patients’ survival has not been reported. To shed light on this problem, we performed an analysis on the relationship between CD24 expression and prognostic parameters in gallbladder carcinoma. CD24 expression was examined immunohistochemically on paraffin-embedded tissue specimens from 207 patients who underwent surgical treatment for gallbladder carcinoma in the period between January 2004 and May 2009. CD24 positive expression was found in 78.7% (163/207) of the tumor samples. It tended to be associated positively with tumor histological grades and pT stages. Kaplan-Meier curves showed that CD24 positive expression was significantly related to decreased overall survival (p<0.01). Multivariate analysis, including CD24 expression, pT stage, tumor grade, and resection margin involvement, showed that CD24 positive expression was an independent prognostic marker in gallbladder carcinoma (p=0.02; relative risk=1.6). Our data demonstrate for the first time that CD24 is an important marker of malignancy and poor prognosis in gallbladder carcinoma. Its detection combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with gallbladder carcinoma. Furthermore, the CD24 antigen represents an attractive target for specific therapies with monoclonal antibodies in patients with CD24-overexpressing gallbladder carcinoma, so the detection of CD24 may help clinicians select patients likely to benefit from novel molecular therapies.
C1 [Liu, Bo] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan Province, China.
[Zhang, Yangde] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Liao, Mingmei] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Deng, Zhansheng] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Gong, Liansheng] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Jiang, Jiarui] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan Province, China.
[Lynn, Ling] Central South University, The Second Xiangya Hospital, Department of Orthopedics, 410011 Changsha, Hunan Province, China.
[Wu, Kai] Central South University, The First Xiangya Hospital, Department of Orthopedics, 410011 Changsha, Hunan Province, China.
[Miao, Xiongying] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan Province, China.
RP Miao, X (reprint author), Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, China.
EM mxymxy126@126.com
CR Roa I, De Aretxabala X, Araya JC et al, 2006, Preneoplastic lesions in gallbladder cancer. J Surg Oncol 93:615–623
Lewis JT, Talwalkar JA, Rosen CB et al, 2003, Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasiacarcinoma sequence. Am J Surg Pathol 31:907–913
Misra S, Chaturvedi A, Misra NC et al, 2003, Carcinoma of the gallbladder. Lancet Oncol 4:167–176
Taguchi T, Kiyokawa N, Mimori K et al, 2003, Pre-B cell antigen receptor-mediated signal inhibits CD24-induced apoptosis in human pre-B cells. J Immunol 170:252–260
Jung KC, Park WS, Kim HJ et al, 2004, TCR independent and caspase-independent apoptosis of murine thymocytes by CD24 cross-linking. J Immunol 172:795–802
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Park JS, Jung WH, Kim JK et al, 2009, Estrogen receptor α, estrogen receptor β, and progesterone receptor as possible prognostic factor in radically resected gallbladder carcinoma. J Surg Res 152:104–110
Varga M, Obrist P, Schneeberger S et al, 2004, Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res 10:3131–3136
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 45
EP 50
DI 10.1007/s12253-010-9278-2
PG 6
ER
PT J
AU Sabbatini, M
Comi, C
Chiocchetti, A
Piffanelli, V
Car, GP
Dianzani, U
Monaco, F
Cannas, M
AF Sabbatini, Maurizio
Comi, Cristoforo
Chiocchetti, Annalisa
Piffanelli, Valentina
Car, Giorgio Pier
Dianzani, Umberto
Monaco, Francesco
Cannas, Mario
TI Signals of Apoptotic Pathways in Several Types of Meningioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caspases; Caspase-inhibitor; Bax; bcl-2; TUNEL
ID Caspases; Caspase-inhibitor; Bax; bcl-2; TUNEL
AB Meningiomas are intracranial tumour derived from meningothelial cells, which aggressive behaviour has been frequently associated to cell apoptosis. In this paper activation of several factors involved in apoptosis has been investigated on biopsies of primary, non recurrent meningiomas. Benign (meningotheliomatous, transitional, fibrous, angiomatous), atypical and anaplastic meningiomas were analysed by immunohistochemistry and western blot, to visualize the occurring of different apoptotic pathways and their association with clinical grading. Apoptotic cell have been detected by a double colorimetric staining for TUNEL and caspase-3 active form. Apoptotic signal positive cells have been detected in all type of meningiomas analysed, with exception of meningotheliomatous meningiomas. Differences have been found in the activation of apoptotic pathways between several types of grade I meningiomas and among benign, anaplastic and atypical meningiomas. An intense expression of several apoptotic inhibitor occurred in grade I meningiomas. The correlation among expression of apoptotic and inhibitory factors and cell proliferation index may suggest that in grade I meningiomas apoptosis may be related to mechanisms involved into tumor cells surviving. Instead in grade II and III meningiomas the same correlation seems indicate an high turnover of tumor cells that might be useful as index of cell proliferation and tumor mass growth.
C1 [Sabbatini, Maurizio] University of Eastern Piedmont, Department of Clinical and Experimental Medicine, Laboratory of Human Anatomy, Via Solaroli 17, 28100 Novara, Italy.
[Comi, Cristoforo] University of Eastern Piedmont, Department of NeurologyNovara, Italy.
[Chiocchetti, Annalisa] University of Eastern Piedmont, Department of Medical Science, Laboratory of ImmunologyNovara, Italy.
[Piffanelli, Valentina] University of Eastern Piedmont, Department of Clinical and Experimental Medicine, Laboratory of Human Anatomy, Via Solaroli 17, 28100 Novara, Italy.
[Car, Giorgio Pier] Ospedale Maggiore della Carita of Novara, Neurosurgery DivisionNovara, Italy.
[Dianzani, Umberto] University of Eastern Piedmont, Department of Medical Science, Laboratory of ImmunologyNovara, Italy.
[Monaco, Francesco] University of Eastern Piedmont, Department of NeurologyNovara, Italy.
[Cannas, Mario] University of Eastern Piedmont, Department of Clinical and Experimental Medicine, Laboratory of Human Anatomy, Via Solaroli 17, 28100 Novara, Italy.
RP Sabbatini, M (reprint author), University of Eastern Piedmont, Department of Clinical and Experimental Medicine, Laboratory of Human Anatomy, 28100 Novara, Italy.
EM maurizio.sabbatini@med.unipmn.it
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 51
EP 59
DI 10.1007/s12253-010-9279-1
PG 9
ER
PT J
AU Legan, M
Tevzic,
Tolar, A
Luzar, B
Marolt, FV
AF Legan, Mateja
Tevzic, Spela
Tolar, Ana
Luzar, Bostjan
Marolt, Ferlan Vera
TI Glucose Transporter-1 (GLUT-1) Immunoreactivity in Benign, Premalignant and Malignant Lesions of the Gallbladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diagnosis; Gallbladder adenocarcinoma; GLUT-1; Immunohistochemistry; Prognosis
ID Diagnosis; Gallbladder adenocarcinoma; GLUT-1; Immunohistochemistry; Prognosis
AB GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, lowgrade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0–10% of cells stained), positive with weak to moderate (10–50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.
C1 [Legan, Mateja] University of Ljubljana, Faculty of Medicine, Institute of Histology and Embryology, Korytkova 2, SI-1000 Ljubljana, Slovenia.
[Tevzic, Spela] University of Ljubljana, Faculty of Medicine, Institute of Histology and Embryology, Korytkova 2, SI-1000 Ljubljana, Slovenia.
[Tolar, Ana] University of Ljubljana, Faculty of Medicine, Institute of Histology and Embryology, Korytkova 2, SI-1000 Ljubljana, Slovenia.
[Luzar, Bostjan] University of Ljubljana, Faculty of Medicine, Institute of PathologyLjubljana, Slovenia.
[Marolt, Ferlan Vera] University of Ljubljana, Faculty of Medicine, Institute of PathologyLjubljana, Slovenia.
RP Legan, M (reprint author), University of Ljubljana, Faculty of Medicine, Institute of Histology and Embryology, SI-1000 Ljubljana, Slovenia.
EM mateja.legan@mf.uni-lj.si
CR Dills WL, 1993, Nutritional and physiological consequences of tumor glycolysis. Parasitology 107:S177–S186
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 61
EP 66
DI 10.1007/s12253-010-9281-7
PG 6
ER
PT J
AU Song, HJ
Cao, Z
Jung, HY
Nam, WS
Kim, YS
Lee, YJ
Park, SW
AF Song, Hwi Jae
Cao, Zhang
Jung, Hwan Yoon
Nam, Woo Suk
Kim, Young Su
Lee, Young Jung
Park, Sang Won
TI Genetic Alterations and Expression Pattern of CEACAM1 in Colorectal Adenomas and Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CEACAM1; Colorectal cancer; Somatic mutation; Expression; Immunohistochemistry
ID CEACAM1; Colorectal cancer; Somatic mutation; Expression; Immunohistochemistry
AB Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on epithelial cells throughout the intestinal tract and is a negative regulator of tumor cell growth, suggesting that it may function as a tumor suppressor. In this study, to determine whether the CEACAM1 is involved in colorectal tumorigenesis, we have investigated the genetic alterations, including mutations and allelic loss, of the CEACAM1 gene in 17 colonic adenomas and 123 sporadic colorectal cancers. In addition, the expression pattern of the CEACAM1 protein was examined in 60 colonic adenomas and 123 sporadic colorectal adenocarcinomas. No mutation was found in colonic adenomas, but four somatic missense mutations, L36F, T312I, V398I and A445V, were detected in colorectal cancers. Interestingly, all of the mutations were found in left-side colon cancers of the patients with clinical stage III. In LOH analysis, nine adenomas were informative for at least one of the markers and five (55.6%) showed allelic loss. Thirty-eight cancers were informative at D19S211 and D19S872 markers and 21 (56.3%) showed LOH at these markers. Statistically, the frequency of allelic loss at the CEACAM1 locus was not associated with clinicopathologic parameters (P>0.05). In immunohistochemical analysis, loss of expression of CEACAM1 protein was detected in nine (15.0%) and 30 (24.4%) of 60 colorectal adenomas and 123 colorectal cancers. Statistically, there was no significant relationship between loss of CEACAM1 expression and clinicopathologic parameters, including clinical stage, tumor location, tumor size, lymph node metastasis and 5-year survival (P>0.05). These data suggest that genetic alteration and loss of expression of the CEACAM1 may contribute to the development of colorectal cancers, as an early event.
C1 [Song, Hwi Jae] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Cao, Zhang] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Jung, Hwan Yoon] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Nam, Woo Suk] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Kim, Young Su] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Lee, Young Jung] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
[Park, Sang Won] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Seocho-gu, 137-701 Seoul, South Korea.
RP Park, SW (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM wonsang@catholic.ac.kr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 67
EP 74
DI 10.1007/s12253-010-9282-6
PG 8
ER
PT J
AU Topic, A
Ljujic, M
Nikolic, A
Petrovic-Stanojevic, N
Dopudja-Pantic, V
Mitic-Milikic, M
Radojkovic, D
AF Topic, Aleksandra
Ljujic, Mila
Nikolic, Aleksandra
Petrovic-Stanojevic, Natasa
Dopudja-Pantic, Vesna
Mitic-Milikic, Marija
Radojkovic, Dragica
TI Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Alpha-1-antitrypsin; Neutrophil elastase; Polymorphisms; Lung cancer
ID Alpha-1-antitrypsin; Neutrophil elastase; Polymorphisms; Lung cancer
AB Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f=0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were −903TT and −741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.
C1 [Topic, Aleksandra] Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, Vojvode Stepe 450, 11221 Belgrade, Serbia.
[Ljujic, Mila] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Nikolic, Aleksandra] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Petrovic-Stanojevic, Natasa] Zvezdara University Medical CenterBelgrade, Serbia.
[Dopudja-Pantic, Vesna] Zvezdara University Medical CenterBelgrade, Serbia.
[Mitic-Milikic, Marija] Clinical Centre of Serbia, Institute for Lung Diseases and TuberculosisBelgrade, Serbia.
[Radojkovic, Dragica] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
RP Topic, A (reprint author), Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, 11221 Belgrade, Serbia.
EM aleksandra.topic1@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 75
EP 80
DI 10.1007/s12253-010-9283-5
PG 6
ER
PT J
AU Olah,
Balogh, E
Pajor, L
Jakab, Zs
AF Olah, Eva
Balogh, Erzsebet
Pajor, Laszlo
Jakab, Zsuzsanna
TI Ten-year Experiences on Initial Genetic Examination in Childhood Acute Lymphoblastic Leukaemia in Hungary (1993–2002). Technical Approaches and Clinical Implementation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALL; Childhood; Chromosome aberration; FISH; Prognostic factor
ID ALL; Childhood; Chromosome aberration; FISH; Prognostic factor
AB A nationwide study was started in 1993 to provide genetic diagnosis for all newly diagnosed childhood ALL cases in Hungary using cytogenetic examination, DNA-index determination, FISH (aneuploidy, ABL/BCR, TEL/AML1) and molecular genetic tests (ABL/BCR, MLL/AF4, TEL/AML1). Aim of the study was to assess the usefullness of different genetic methods, to study the frequency of various aberrations and their prognostic significance. Results were synthesized for genetic subgrouping of patients. To assess the prognostic value of genetic aberrations overall and event-free survival of genetic subgroups were compared using Kaplan-Meier method. Prognostic role of aberrations was investigated by multivariate analysis (Cox’s regression) as well in comparison with other factors (age, sex, major congenital abnormalities, initial WBC, therapy, immunophenotype). Five hundred eighty-eight ALL cases were diagnosed between 1993–2002. Cytogenetic examination was performed in 537 (91%) (success rate 73%), DNA-index in 265 (45%), FISH in 74 (13%), TEL/AML1 RT-PCR in 219 (37%) cases producing genetic diagnosis in 457 patients (78%). Proportion of subgroups with good prognosis in prae-B-cell ALL was lower than expected: hyperdiploidB 18% (73/400), TEL/AML1+ 9% (36/400). Univariate analysis showed significantly better 5-year EFS in TEL/AML1+ (82%) and hyperdiploidB cases (78%) than in tetraploid (44%) or pseudodiploid (52%) subgroups. By multivariate analysis main negative prognostic factors were: congenital abnormalities, high WBC, delay in therapy, specific translocations. Conclusion: Complementary use of each of genetic methods used is necessary for reliable genetic diagnosis according to the algorythm presented. Specific genetic alterations proved to be of prognostic significance.
C1 [Olah, Eva] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98 Nagyerdei krt, 4012 Debrecen, Hungary.
[Balogh, Erzsebet] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 98 Nagyerdei krt, 4012 Debrecen, Hungary.
[Pajor, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Jakab, Zsuzsanna] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
RP Olah, (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, 4012 Debrecen, Hungary.
EM eolah@dote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 81
EP 90
DI 10.1007/s12253-010-9286-2
PG 10
ER
PT J
AU Agrawal, U
Mishra, KA
Salgia, P
Verma, S
Mohanty, KN
Saxena, S
AF Agrawal, Usha
Mishra, K Ashwani
Salgia, Payal
Verma, Saurabh
Mohanty, K Nayan
Saxena, Sunita
TI Role of Tumor Suppressor and Angiogenesis Markers in Prediction of Recurrence of Non Muscle Invasive Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non muscle invasive bladder cancer; Biomarkers; Predictive role; Survival analysis; Hazard ratio
ID Non muscle invasive bladder cancer; Biomarkers; Predictive role; Survival analysis; Hazard ratio
AB Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a χ2 and Fisher’s Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105 [2.624(1.274-5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993-4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148-4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611 (1.189-5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021-5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n=33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours.
C1 [Agrawal, Usha] Indian Council of Medical Research (ICMR), Institute of Pathology, Safdarjung Hospital Campus, 110029 New Delhi, India.
[Mishra, K Ashwani] Indian Council of Medical Research (ICMR), Institute of Pathology, Safdarjung Hospital Campus, 110029 New Delhi, India.
[Salgia, Payal] Indian Council of Medical Research (ICMR), Institute of Pathology, Safdarjung Hospital Campus, 110029 New Delhi, India.
[Verma, Saurabh] Indian Council of Medical Research (ICMR), Institute of Pathology, Safdarjung Hospital Campus, 110029 New Delhi, India.
[Mohanty, K Nayan] Safdarjung Hospital, Department of Urology, 110029 New Delhi, India.
[Saxena, Sunita] Indian Council of Medical Research (ICMR), Institute of Pathology, Safdarjung Hospital Campus, 110029 New Delhi, India.
RP Saxena, S (reprint author), Indian Council of Medical Research (ICMR), Institute of Pathology, 110029 New Delhi, India.
EM sunita_saxena@yahoo.com
CR Consolidated Report of Population Based Cancer Registries 2001–2004, Incidence and Distribution of Cancer, 2006, National Cancer Registry Programme. Indian Council of Medical Research, ICMR). Bangalore
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 91
EP 101
DI 10.1007/s12253-010-9287-1
PG 11
ER
PT J
AU Mammas, NI
Sourvinos, G
Zaravinos, A
Spandidos, AD
AF Mammas, N Ioannis
Sourvinos, George
Zaravinos, Apostolos
Spandidos, A Demetrios
TI Vaccination against Human Papilloma Virus (HPV): Epidemiological Evidence of HPV in Non-genital Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HPV; Non-genital cancer; Oesophageal; Laryngeal; Oropharyngeal; Lung; Urothelial; Breast; Colon; Vaccination; Childhood
ID HPV; Non-genital cancer; Oesophageal; Laryngeal; Oropharyngeal; Lung; Urothelial; Breast; Colon; Vaccination; Childhood
AB Recently, the vaccine against human papillomavirus (HPV) was introduced in the national vaccination programmes of several countries worldwide. The established association between HPV and the progression of cervical neoplasia provides evidence of the expected protection of the vaccine against cervical cancer. During the last two decades several studies have also examined the possible involvement of HPV in non-genital cancers and have proposed the presence of HPV in oesophageal, laryngeal, oropharyngeal, lung, urothelial, breast and colon cancers. The possible involvement of HPV in these types of cancer would necessitate the introduction of the vaccine in both boys and girls. However, the role of HPV in the pathogenesis of these types of cancer has yet to be proven. Moreover, the controversial evidence of the possible impact of the vaccination against HPV in the prevention of non-genital cancers needs to be further evaluated. In this review, we present an overview of the existing epidemiological evidence regarding the detection of HPV in non-genital cancers.
C1 [Mammas, N Ioannis] University of Crete, Medical School, Department of VirologyHeraklion, Greece.
[Sourvinos, George] University of Crete, Medical School, Department of VirologyHeraklion, Greece.
[Zaravinos, Apostolos] University of Crete, Medical School, Department of VirologyHeraklion, Greece.
[Spandidos, A Demetrios] University of Crete, Medical School, Department of VirologyHeraklion, Greece.
RP Spandidos, AD (reprint author), University of Crete, Medical School, Department of Virology, Heraklion, Greece.
EM spandidos@spandidos.gr
CR zur Hausen H, 2002, Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350
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Akil N, Yasmeen A, Kassab A et al, 2008, High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study. Br J Cancer 99:404–407
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de Cremoux P, Thioux M, Lebigot I, Sigal-Zafrani B, Salmon R, Sastre-Garau X, Institut Curie Breast Group, 2008, No evidence of human papillomavirus DNA sequences in invasive breast carcinoma. Breast Cancer Res Treat 109:55–58
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Bratthauer GL, Tavassoli FA, O’Leary TJ, 1992, Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/ 16/18. Pathol Res Pract 188:384–386
Widschwendter A, Brunhuber T, Wiedemair A et al, 2004, Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history. J Clin Virol 31:292–297
Hennig EM, Di Lonardo A, Venuti A, Holm R et al, 1999, HPV 16 in multiple neoplastic lesions in women with CIN III. J Exp Clin Cancer Res 18:369–377
Damin DC, Caetano MB, Rosito MA et al, 2007, Evidence for an association of human papillomavirus infection and colorectal cancer. Eur J Surg Oncol 33:569–574
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Kirgan D, Manalo P, McGregor B, 1990, Immunohistochemical demonstration of human papilloma virus antigen in human colon neoplasms. J Surg Res 48:397–402
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 103
EP 119
DI 10.1007/s12253-010-9288-0
PG 17
ER
PT J
AU Elhefnawy, GN
AF Elhefnawy, Galal Nadia
TI Contribution of Electron Microscopy to the Final Diagnosis of Renal Biopsies in Egyptian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal biopsy; Glomerulonephritis; Electron microscopy
ID Renal biopsy; Glomerulonephritis; Electron microscopy
AB There are few publications studying the impact and cost benefit relationship of electron microscopy in the diagnosis of glomerulopathies in routine service. The aim of this study is to assess the contribution of EM to the final diagnosis of renal glomerular diseases in Egyptian patients. Retrospective evaluation of 120 renal biopsy specimens received for primary diagnosis at EM center of Ain Shams university Specialized hospital, Cairo Egypt during 2007in the knowledge of light microscopic, immunofluorescence and electron microscopic findings. It was found that EM was essential for diagnosis in 25% of renal biopsies, corresponding to 100% of hereditary glomerulopathies and 23.5% of other glomerulopathies, It was useful to the dignosis in 41.67% of the cases, confirming the preliminary diagnosis. In 33.33% of cases EM was considered unhelpful in diagnosis. It’s concluded that the importance of EM has not decreased during the last years. New glomerular diseases and variants can be diagnosed only by EM as fibrillary glomerulonephritis and immunotactoid glomerulopathy. Routine evaluation of allograft biopsies should include EM to achieve better recognition of capillary lesions of chronic rejection. EM provides useful diagnostic information in about 66% of native renal biopsies. Kidney biopsy protocols should include EM in all biopsy cases. If electron microscopy cannot be performed routinely on all such biopsies, tissue should be reserved for EM studies.
C1 [Elhefnawy, Galal Nadia] Ain Shams Faculty of Medicine, Department of Pathology, 11811 Cairo, Egypt.
RP Elhefnawy, GN (reprint author), Ain Shams Faculty of Medicine, Department of Pathology, 11811 Cairo, Egypt.
EM n.ga.lal@hotmail.com
CR Jennette JC, Olson JL, Schwartz MM, Silva FG, 2007, Primer on the diagnosis of renal disease. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, eds, Heptinstall’s pathology of the kidney, 6th edn. Lippincott Williams & Wilkins publishers, p 108
Tucker JA, 2000, The continuing value of electron microscopy in surgical pathology. Ultrastruct Pathol 24(6):383–389
Tighe JR, Jones NF, 1970, The diagnostic value of routine electron microscopy of renal biopsies. Proc R Soc Med 63, 5):475–477
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Siegel NJ, Spargo BH, Kashgarian M, Hayslett JP, 1973, An evaluation of routine electron microscopy in the examination of renal biopsies. Nephron 10(4):209–215
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Pearson JM, McWilliam LJ, Coyne JD, Curry A, 1994, Value of electron microscopy in diagnosis of renal disease. J Clin Pathol 47, 2):126–128
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Wang S, Zhan Y, Zou W, 1998, The evaluation of electron microscopy in the pathological diagnosis of renal biopsies. Zonghua yi xue za zhi 78(10):782–784
Sementilli A, Moura LA, Franco MF, 2004, The role of electron microscopy for the diagnosis of glomerulopathies. Sao Paulo Med J, Vol. No.3
Collan Y, Hirsimaki P, Aho H, Wuorela M, Sundstom J, Tertti R, Metsrinne K, 2005, Ultrastruct Pathol 29(6):461–468
Rivera A, Magliato S, Meleg-Smith S, 2001, Value of electron microscopy in the diagnosis of childhood nephrotic syndrome. Ultrastruct Pathol 313–320
Strife CF, Mc Adams AJ, West CD, 1982, Membranoproliferative glomerulonephritis characterized by focal segmental proliferation. Clin Nephrol 18:9
Zhou XJ, Silva FG, 2007, Membranoproliferative glomerulonephritis. In: Jennette JC, Olson JL, Schwartz M, Silva FG, eds, Heptinstall’s pathology of the kidney, 6th edn. Lippincott Williams & Wilkins publishers, p 277
HerraraGA, 1999, The value of electronmicroscopy in the diagnosis and clinical management of lupus nephritis. Ultrastruct Pathol 23:63
Grande JP, Balow JE, 1998, Renal biopsy in lupus nephritis. Lupus 7(9):611–617
Herrara GA, Isaac J, Turbet-Herrara EA, 2009, Role of electon microscopy in transplant renal pathology. Ultrastruct Pathol 21, 6):481–498
Ivanyi B, Kemeny E, Szederkenyi E, Marofka F, Szenohradszky P, 2001, The role of electron microscopy in the diagnosis of chronic renal allograft rejection. Mod Pathol 3; 14(12):1200– 1208
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 121
EP 125
DI 10.1007/s12253-010-9290-6
PG 5
ER
PT J
AU Jiang, Y
Long, H
Wang, W
Liu, H
Tang, Y
Zhang, X
AF Jiang, Yong
Long, Hu
Wang, Weiya
Liu, Huawei
Tang, Yuan
Zhang, Xiuhui
TI Clinicopathological Features and Immunoexpression Profiles of Goblet Cell Carcinoid and Typical Carcinoid of the Appendix
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Appendiceal neoplasm; CEA; CgA; CK7; CK20; Immunohistochemistry; Goblet cell carcinoid; Ki67; P63; Typical carcinoid
ID Appendiceal neoplasm; CEA; CgA; CK7; CK20; Immunohistochemistry; Goblet cell carcinoid; Ki67; P63; Typical carcinoid
AB Goblet cell carcinoid (GCC) of the appendix is currently classified as a neuroendocrine tumor, together with typical carcinoid (TC) of the appendix. However, whether GCC is a variant of TC or a mucin-producing adenocarcinoma is still controversial. To get a better understanding, we investigated the clinicopathological features of 55 Chinese patients (26 GCCs and 29 TCs), and explored the histochemical properties and expression profiles of CK7, CK20, P63, CEA, CgA, NSE, CD56, and Ki67 in 37 out of these 55 patients (18 GCCs and 19 TCs). Our results showed GCC had a male predominance, older age involvement, significantly larger tumor size, and significantly more frequency of mesoappendix infiltration than TC. Alcian blue/PAS stains were positive in all the GCC cases, while negative in all the TC cases. CK7 and CK20 expressions were significantly more frequent in GCC (P=0.03 and 0.00001, respectively). However, P63 expression was detected in none of the GCC cases but in 6 TC cases (P=0.02). Although the expression of CgA was similar, strong expression (3+) was significantly more frequent in TC (P=5.7×10−11). Also, NSE and CD56 expressions were significantly more frequent in TC (P=0.02 and 1.26×10−4, respectively). CEA expression was significantly more frequent in GCC (P=2.4×10−6). Finally, Ki67 index was low in GCC (4.7%), but significantly higher than TC (0.9%) (P=5.4×10−6). Taken together, these distinct features support that GCC differs from TC, a classical neuroendocrine tumor, and harbors an immunophenotype of adenocarcinoma. Therefore, the term "low grade adenocarcinoma with neuroendocrine differentiation" might be more appropriate for GCC.
C1 [Jiang, Yong] Sichuan University, West China Hospital, Department of Pathology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan, China.
[Long, Hu] Sichuan University, West China College of Stomatology, 610041 Chengdu, Sichuan, China.
[Wang, Weiya] Sichuan University, West China Hospital, Department of Pathology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan, China.
[Liu, Huawei] Sichuan University, West China School of Medicine, 610041 Chengdu, Sichuan, China.
[Tang, Yuan] Sichuan University, West China Hospital, Department of Pathology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan, China.
[Zhang, Xiuhui] Sichuan University, West China Hospital, Department of Pathology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan, China.
RP Zhang, X (reprint author), Sichuan University, West China Hospital, Department of Pathology, 610041 Chengdu, China.
EM xiuhui_zhang@yahoo.com
CR Capella C, Solcia E, Sobin LH,Arnold R, 2000, Endocrine tumors of the appendix. World Health Organization Classification of Tumours. Pathology and genetics of tumours of the digestive system. In: Hamilton SR, Aaltonen LA, ed, IARC Press, Lyon, pp 99–101
Pahlavan PS, Kanthan R, 2005, Goblet cell carcinoid of the appendix. World J Surg Oncol 3:36
Kanthan R, Saxena A, Kanthan SC, 2001, Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural study. Arch Pathol Lab Med 125(3):386–90
Park K, Blessing K, Kerr K, Chetty U, Gilmour H, 1990, Goblet cell carcinoid of the appendix. Gut 31:322–324
Deans GT, Spence RA, 1995, Neoplastic lesions of the appendix. Br J Surg 82:299–306
Butler TA, Houshiar A, Lin F, Wilson SE, 1994, Goblet cell carcinoid of the appendix. Am J Surg 168:685–687
Alsaad KO, Serra S, Schmitt A, Perren A, Chetty R, 2007, Cytokeratins 7 and 20 immunoexpression profile in goblet cell and classical carcinoids of appendix. Endocr Pathol 18(1):16–22
van Eeden S, Offerhaus GJ, Hart AA et al, 2007, Goblet cell carcinoid of the appendix: a specific type of carcinoma. Histopathology 51(6):763–73
Ramnani DM, Wistuba II, Behrens C et al, 1999, K-ras and p53 mutations in the pathogenesis of classical and goblet cell carcinoids of the appendix. Cancer 86(1):14–21
Stancu M, Wu TT, Wallace C et al, 2003, Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors. Mod Pathol 16(12):1189–98
Subbuswamy SG, Gibbs NM, Ross CF, Morson BC, 1974, Goblet cell carcinoid of the appendix. Cancer 34(2):338–44
Kende AI, Carr NJ, Sobin LH, 2003, Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract. Histopathology 42(2):137–40
Toumpanakis C, Standish RA, Baishnab E, Winslet MC, Caplin ME, 2007, Goblet cell carcinoid tumors, adenocarcinoid, of the appendix. Dis Colon Rectum 50(3):315–22
Wang BY, Gil J, Kaufman D et al, 2002, P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol 33(9):921–6
Owens SR, Greenson JK, 2007, Immunohistochemical staining for p63 is useful in the diagnosis of anal squamous cell carcinomas. Am J Surg Pathol 31(2):285–90
Sokmensuer C, Gedikoglu G, Uzunalimoglu B, 2001, Importance of proliferation markers in gastrointestinal carcinoid tumors: a clinicopathologic study. Hepatogastroenterology 48(39):720–3
Li CC, Hirowaka M, Qian ZR, Xu B, Sano T, 2002, Expression of E-cadherin, b-catenin, and Ki-67 in goblet cell carcinoids of the appendix: an immunohistochemical study with clinical correlation. Endocr Pathol 13(1):47–58
McCusker ME, Cote TR, Clegg LX, Sobin LH, 2002, Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer 94(12):3307–12
Konishi T, Watanabe T, Muto T, Kotake K, Nagawa H, 2006, Site distribution of gastrointestinal carcinoids differs between races. Gut 55(7):1051–2
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 127
EP 132
DI 10.1007/s12253-010-9291-5
PG 6
ER
PT J
AU Warchol, T
Kruszyna,
Lianeri, M
Roszak, A
Jagodzinski, PP
AF Warchol, Teresa
Kruszyna, Lukasz
Lianeri, Margarita
Roszak, Andrzej
Jagodzinski, P Pawel
TI Distribution of CCND1 A870G Polymorphism in Patients with Advanced Uterine Cervical Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical carcinoma; CCND1; Polymorphism
ID Cervical carcinoma; CCND1; Polymorphism
AB We examined the distribution of the CCND1 A870G (rs9344) polymorphic variant in patients with cervical cancer (n=129) and healthy individuals (n=288) in a sample of a Polish cohort. We showed that patients with advanced cervical cancer bearing the CCND1 A/A and A/G genotypes displayed a 1.811-fold increased risk of cervical cancer (95% CI=1.150–2.852, p=0.0098). We also found a significantly higher frequency of the CCND1 870A allele in patients with cancer than in controls, p=0.0116. Our investigation confirmed that the CCND1 870A gene variant may be a genetic risk factor in the incidence of advanced cervical cancer.
C1 [Warchol, Teresa] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Kruszyna, Lukasz] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Lianeri, Margarita] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Roszak, Andrzej] Greater Poland Cancer Center, Department of Radiotherapy and Gynecological OncologyPoznan, Poland.
[Jagodzinski, P Pawel] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
RP Jagodzinski, PP (reprint author), Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznan, Poland.
EM pjagodzi@am.poznan.pl
CR Parkin DM, Bray F, Ferlay J, Pisani P et al, 2005, Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Parkin DM, Bray F, 2006, Chapter 2: the burden of HPV-related cancers. Vaccine 24(S3):11–25
Munoz N, Bosch FX, de Sanjose S et al, 2003, Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527
Baseman JG, Koutsky LA, 2005, The epidemiology of human papillomavirus infections. J Clin Virol 32(Suppl 1):S16–24
Magnusson PK, Sparen P, Gyllensten UB, 1999, Genetic link to cervical tumours. Nature 400:29–30
Hemminki K, Dong C, Vaittinen P, 1999, Familial risks in cervical cancer: is there a hereditary component? Int J Cancer 82:775–781
Hemminki K, Chen B, 2006, Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol BiomarkersPrev 15:1413–1414
Kim JK, Diehl JA, 2009, Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol 220:292–296
Hall M, Peters G, 1996, Genetic alterations of cyclins, cyclindependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res 68:67–108
Wang L, Habuchi T, Mitsumori K et al, 2003, Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism. Int J Cancer 103:116–120
Onay UV, Aaltonen K, Briollais L et al, 2008, Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk. BMC Cancer 8:6
Le Marchand L, Seifried A, Lum-Jones A et al, 2003, Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer. JAMA 290:2843–2848
Rydzanicz M, Golusinski P, Mielcarek-Kuchta D et al, 2006, Cyclin D1 gene, CCND1, polymorphism and the risk of squamous cell carcinoma of the larynx. Eur Arch Otorhinolaryngol 263:43–48
Izzo JG, Malhotra U, Wu TT et al, 2005, Impact of cyclin D1 A870G polymorphism in esophageal adenocarcinoma tumorigenesis. Semin Oncol 32:S11–5
Hou X, Wang S, Zhou Y et al, 2005, Cyclin D1 gene polymorphism and susceptibility to childhood acute lymphoblastic leukemia in a Chinese population. Int J Hematol 82:206–209
Castro FA, Haimila K, Sareneva I et al, 2009, Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population–a candidate gene approach. Int J Cancer 125:1851–1858
Thakur N, Hussain S, Kohaar I et al, 2009, Genetic variant of CCND1: association with HPV-mediated cervical cancer in Indian population. Biomarkers 14:219–225
Satinder K, Chander SR, Pushpinder K et al, 2008, Cyclin D1, G870A, polymorphism and risk of cervix cancer: a case control study in north Indian population. Mol Cell Biochem 315:151–157
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Jeon YT, Kim JW, Song JH et al, 2005, Cyclin D1 G870A polymorphism and squamous cell carcinoma of the uterine cervix in Korean women. Cancer Lett 223:259–263
Catarino R, Matos A, Pinto D et al, 2005, Increased risk of cervical cancer associated with cyclin D1 gene A870G polymorphism. Cancer Genet Cytogenet 160:49–54
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Pabalan N, Bapat B, Sung L et al, 2008, Cyclin D1 Pro241Pro, CCND1-G870A, polymorphism is associated with increased cancer risk in human populations: a meta-analysis. Cancer Epidemiol Biomarkers Prev 17:2773–2781
Huh K, Zhou X, Hayakawa H et al, 2007, Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor. J Virol 81:9737–9747
Huh KW, DeMasi J, Ogawa H et al, 2005, Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proc Natl Acad Sci U S A 102:11492–11497
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 133
EP 137
DI 10.1007/s12253-010-9293-3
PG 5
ER
PT J
AU de Armas, Y
Capo, V
Gonzalez, I
Mederos, L
Diaz, R
de Waard, HJ
Rodriguez, A
Garcia, Y
Cabanas, R
AF de Armas, Yaxsier
Capo, Virginia
Gonzalez, Ida
Mederos, Lilian
Diaz, Raul
de Waard, H Jacobus
Rodriguez, Alberto
Garcia, Yarmila
Cabanas, Ricardo
TI Concomitant Mycobacterium avium Infection and Hodgkin’s Disease in a Lymph Node from an HIV-negative Child
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Mycobacterium avium; Hodgkin’s disease; PCR
ID Mycobacterium avium; Hodgkin’s disease; PCR
AB We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin’s disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.
C1 [de Armas, Yaxsier] Institute of Tropical MedicineHavana City, Cuba.
[Capo, Virginia] Institute of Tropical MedicineHavana City, Cuba.
[Gonzalez, Ida] Institute of Tropical MedicineHavana City, Cuba.
[Mederos, Lilian] Institute of Tropical MedicineHavana City, Cuba.
[Diaz, Raul] Institute of Tropical MedicineHavana City, Cuba.
[de Waard, H Jacobus] Instituto de BiomedicinaCaracas, Venezuela.
[Rodriguez, Alberto] Limonar County HospitalLimonar, Matanzas Province, Cuba.
[Garcia, Yarmila] Juan Manuel Marquez HospitalHavana City, Cuba.
[Cabanas, Ricardo] Juan Manuel Marquez HospitalHavana City, Cuba.
RP de Armas, Y (reprint author), Institute of Tropical Medicine, Havana City, Cuba.
EM Yaxsier@ipk.sld.cu
CR Jarzembowski JA, Young MB, 2008, Nontuberculous mycobacterial infections. Arch Pathol Lab Med 132:1333–1341
Rosenberg SA, Kaplan HS, 1966, Evidence for an orderly progression in the spread of Hodgkin’s disease. Cancer Res 26:1225–1231
Karakas Z, Agaoglu L, Taravari B et al, 2003, Pulmonary tuberculosis in children with Hodgkin’s lymphoma. Hematol J 4:78–81
Centkowski P, Sawczuk-Chabin J, Prochorec M, Warzocha K, 2005, Hodgkin’slymphoma and tuberculosis coexistence in cervical lymph nodes. Leuk Lymphoma 46:471–475
Telenti A, Marchesi F, Balz M, Bally F, Bottger EC, Bodmer T, 1993, Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis. J Clin Microbiol 31:175–178
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Brousset P, Marchou B, Chittal SM, Delsol G, 1994, Concomitant. Mycobacterium avium complex infection and Epstein-Barr virus associated Hodgkin’s disease in a lymph node from a patient with AIDS. Histopathology 24:586–588
Schulz S, Cabras AD, Kremer M et al, 2005, Species identification of mycobacteria in paraffin-embedded tissues: frequent detection of nontuberculous mycobacteria. Modern Pathol 18:274–282
Thegerstrom J, Romanus V, Friman V, Brudin L, Haeming PD, Olsen B, 2008, Mycobacterium avium lymphadenopathy among children, Sweden. Emerg Infect Dis 14:661–663
Falkinham JO III, 1996, Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 9:177–215
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 139
EP 140
DI 10.1007/s12253-010-9275-5
PG 2
ER
PT J
AU Demeter, J
Istenes, I
Fodor, A
Paksi, M
Dombi, P
Valasinyoszki, E
Csomor, J
Matolcsy, A
Nagy, GZs
AF Demeter, Judit
Istenes, Ildiko
Fodor, Aniko
Paksi, Melinda
Dombi, Peter
Valasinyoszki, Erika
Csomor, Judit
Matolcsy, Andras
Nagy, G Zsolt
TI Efficacy of Romiplostim in the Treatment of Chemotherapy Induced Thrombocytopenia (CIT) in a Patient with Mantle Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Chemotherapy; Lymphoma; Thrombocytopenia; Romiplostim
ID Chemotherapy; Lymphoma; Thrombocytopenia; Romiplostim
AB Chemotherapy induced thrombopenia (CIT) is difficult to treat, as previous treatment options, including recombinant human thrombopoietin proved to be of limited efficacy. Here we report a case of a mantle cell lymphoma patient treated with intensive chemotherapy, who belongs to Yehova’s witnesses and therefore did not accept platelet transfusions. At the time of severe thrombocytopenia (zero thrombocytes/ per mikroliter) and gastrointestinal bleeding, on day 13 following the start of hyperCVAD B chemotherapy, romiplostim treatment was given resulting in quick normalisation of the platelet count followed by thrombocytosis. Based on our observation in further studiesmodification of the dose and timing of romiplostim injection in CIT should be considered.
C1 [Demeter, Judit] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, 1083 Budapest, Hungary.
[Istenes, Ildiko] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, 1083 Budapest, Hungary.
[Fodor, Aniko] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, 1083 Budapest, Hungary.
[Paksi, Melinda] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, 1083 Budapest, Hungary.
[Dombi, Peter] Szent Borbala Hospital, Department of HematologyTatabanya, Hungary.
[Valasinyoszki, Erika] Szent Borbala Hospital, Department of HematologyTatabanya, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Nagy, G Zsolt] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor utca 2/A, 1083 Budapest, Hungary.
RP Demeter, J (reprint author), Semmelweis University, 1st Department of Internal Medicine, 1083 Budapest, Hungary.
EM demjud@bel1.sote.hu
CR Levy B, Arnason JE, Bussel JB, 2008, The use of secondgeneration thrombopoietic agents for chemotherapy-induced thrombocytopenia. Curr Opin Oncol 20:690–696
Natale R, Charu V, Schutte W et al, 2009, Safety of romiplostim for treatment of chemotherapy-induced thrombocytopenia, CIT, in patients with advanced non-small cell lung cancer, NSCLC). Eur J Cancer Suppl 7:574
Fanale M, Stiff P, Noonan K et al, 2009, Safety of romiplostim for treatment of severe chemotherapy induced thrombocytopenia, CIT, in patients with lymphoma receiving multi-cycle chemotherapy: results from an open-label dose- and schedule-finding study. Eur J Cancer Suppl 7:562
Dalal S, Boddapati M, Lowery MN et al, 2006, Treatment of acute myeloid leukemia in a Jehovah’s Witness. Ann Hematol 85:407– 408
Nash MJ, Cohen H, 2004, Management of Jehovah's Witness patients with haematological problems. Blood Rev 18:211–7
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 141
EP 143
DI 10.1007/s12253-010-9276-4
PG 3
ER
PT J
AU Rekhi, B
Folpe, LA
Deshmukh, M
Jambhekar, AN
AF Rekhi, Bharat
Folpe, L Andrew
Deshmukh, Mahesh
Jambhekar, Ajit Nirmala
TI Sclerosing Epithelioid Fibrosarcoma–A Report of Two Cases with Cytogenetic Analysis of FUS Gene Rearrangement by FISH Technique
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sclerosing epithelioid fibrosarcoma; Low-grade fibromyxoid sarcoma; Soft tissue sarcomas; FISH technique; FUS rearrangement
ID Sclerosing epithelioid fibrosarcoma; Low-grade fibromyxoid sarcoma; Soft tissue sarcomas; FISH technique; FUS rearrangement
AB Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma. Recently, a link has been suggested between SEF and low-grade fibromyxoid sarcoma (LGFMS) on the basis of the finding of the characteristic translocation t(7;16) (FUS-CREB3L2) of LGFMS in a small number of studied cases of SEF. The frequency of this translocation in SEF is still unknown. We present 2 cases of SEF with cytogenetic analysis for FUS rearrangement. The tumors occurred in 12 and 58 year old patients, respectively and consisted of a well to partially circumscribed, non-encapsulated mass, comprising monomorphic, polygonal cells arranged in aggregates, cords and single file arrays in a variably sclerotic stroma. The cells exhibited minimal nuclear atypia with moderate amount of clear to eosinophilic cytoplasm and rare mitotic figures. One case also showed bland spindle cell areas with myxoid change, as seen in LGFMS. By immunohistochemistry (IHC), the tumor cells were diffusely positive for vimentin, focally for S-100 in 1 case and negative for cytokeratin (CK), epithelial membrane antigen (EMA), HMB-45, desmin, smooth muscle actin (SMA), H-caldesmon, Myo D-1, CD34 and CD 168. By fluorescent in-situ hybridization (FISH) technique, the case with mixed SEF and LGFMS histology was positive for FUS rearrangement. Our study reinforces the previously reported relationship between SEF and LGFMS, and suggests that SEF may represent a variant of LGFMS in at least some cases, rather than an entirely distinct fibrosarcoma variant.
C1 [Rekhi, Bharat] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Folpe, L Andrew] Mayo Clinic, Department of Laboratory Medicine and Pathology, 200 First Street SW, 55905 Rochester, MN, USA.
[Deshmukh, Mahesh] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Jambhekar, Ajit Nirmala] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
RP Rekhi, B (reprint author), Tata Memorial Hospital, Department of Pathology, 400012 Mumbai, India.
EM rekhi.bharat@gmail.com
CR Meis-Kindblom JM, Kindblom LG, van den Berg E, Molennar WM, 2002, Tumors of soft tissue and bone. Pathology and genetics. In: Fletcher CDM, Unni K, Mertens F, eds, World Health Organization classification of tumors. IARC, Lyon, pp 200–204
Antonescu CR, Rosenblum MK, Pereira P, Nascimento AG, Woodruff JM, 2001, Sclerosing epithelioid fibrosarcoma; a study of 16 cases and confirmation of a clinically distinct tumor. Am J Surg Pathol 25:699–709
Meis-Kindblom JM, Kindblom LG, Enzinger FM, 1995, Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating a carcinoma. Am J Pathol 19:979–993
Eyden BP, Manson C, Banerjee SS, Roberts ISD, Harris M, 1998, Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria. Histopathology 33:354–360
Chow LTC, Lui YH, Kumta SM, Allen PW, 2004, Primary sclerosing epithelioid fibrosarcoma of the sacrum: a case report and review of the literature. J Clin Pathol 57:90–94
Smith P, Almeida B, Krajacevic TB, 2008, Sclerosing epithelioid fibrosarcoma as a rare cause of ascites in a young man; a case report. J Med Case reports 2:248
Guillou L, Benhattar J, Gengler C, Gallagher G, Ranchere-Vince D, Collin F, Terrier P, Terrier-Lacombe MJ, Leroux A, Marques B, Aubain Somerhausen Nde S, Keslair F, Pedeutour F, Coindre JM, 2007, Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 31:1387–1402
Medeiros F, Erickson-Johnson MR, Keeney GL, Clayton AC, Nascimento AG, Wang X, Oliveira AM, 2007, Frequency and characterization of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tract. Genes Chromosomes Cancer 46:981–990
Reid R, de Silva MV, Paterson L, Ryan E, Fisher C, 2003, Lowgrade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11, translocation. Am J Surg Pathol 27:1229–1236
Folpe AL, Weiss SW, 2003, Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants. Am J Surg Pathol 27:421– 431
Folpe AL, Goldblum JR, Rubin BP, Shehata BM, Liu W, Dei Tos AP, Weiss SW, 2005, Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 29:1025–1033
Folpe AL, McKenney JK, Bridge JA, Weiss SW, 2002, Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. Am J Surg Pathol 26:1175–1183
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 145
EP 148
DI 10.1007/s12253-010-9277-3
PG 4
ER
PT J
AU Patrelli, ST
Silini, ME
Berretta, R
Thai, E
Gizzo, S
Bacchi Modena, A
Nardelli, BG
AF Patrelli, Silvio Tito
Silini, Maria Enrico
Berretta, Roberto
Thai, Elena
Gizzo, Salvatore
Bacchi Modena, Alberto
Nardelli, Battista Giovanni
TI Squamotransitional Cell Carcinoma of the Vagina: Diagnosis and Clinical Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Squamotransitional cell carcinoma; Transitonal cell carcinoma; HPV-DNA; Immunohistochemistry; Vagina; Cervix; Endometrium; Urogenital tract; Urothelial carcinoma; Squamous carcinoma
ID Squamotransitional cell carcinoma; Transitonal cell carcinoma; HPV-DNA; Immunohistochemistry; Vagina; Cervix; Endometrium; Urogenital tract; Urothelial carcinoma; Squamous carcinoma
AB Primary squamotransitional cell carcinoma (STCC) is rare squamous cell tumor variant resembling transitional cell carcinoma (TCC) of the urinary tract. STCC occurs rarely in the vagina and its clinical and pathological correlates are poorly known. We report a unique case of a 66-year-old Italian woman with STCC of the vagina. A biopsy of the tumor was performed. The tumor qualified as a STCC. Following biopsy, the patient underwent radical hysterectomy (Piver’s III-type) with bilateral salpingo-oophorectomy, upper colpectomy, appendicectomy, peritoneal cytology, and lymphadenectomy. The patient is now healthy without evidence of recurrence at 30 months after surgery. Pathologically, cytoarchitectural characteristics distinguish this histotype (STCC) from conventional squamous cell carcinoma of the genital tract. The cytokeratin staining pattern (CK7 positive and CK20 negative), the p63 expression and the positivity for p16ink4a and high-risk HPV are the main elements of differential diagnosis. We suggest that STCC of the vagina should be treated by radical surgery, possibly followed by adjuvant therapy based on staging results and should receive a long-term follow-up.
C1 [Patrelli, Silvio Tito] University of Parma, Ob/Gyn Clinic, Via Gramsci, 14, 43100 Parma, Italy.
[Silini, Maria Enrico] University of Parma, Institute of PathologyParma, Italy.
[Berretta, Roberto] University of Parma, Ob/Gyn Clinic, Via Gramsci, 14, 43100 Parma, Italy.
[Thai, Elena] University of Parma, Institute of PathologyParma, Italy.
[Gizzo, Salvatore] University of Parma, Ob/Gyn Clinic, Via Gramsci, 14, 43100 Parma, Italy.
[Bacchi Modena, Alberto] University of Parma, Ob/Gyn Clinic, Via Gramsci, 14, 43100 Parma, Italy.
[Nardelli, Battista Giovanni] University of Parma, Ob/Gyn Clinic, Via Gramsci, 14, 43100 Parma, Italy.
RP Patrelli, ST (reprint author), University of Parma, Ob/Gyn Clinic, 43100 Parma, Italy.
EM titosilvio.patrelli@gmail.com
CR Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ, 2009, Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249
Peters WA III, Kuman NB, Morley GW, 1985, Carcinoma of the vagina. Cancer 55:892–897
Rubin SC, Young J, Mikuta JJ, 1985, Squamous carcinoma of the vagina: treatment, complications, and long term follow-up. Gynecol Oncol 20:346–353
Benedet JL, Murphy KJ, Fairey RN, Boyes DA, 1983, Primary invasive carcinoma of the vagina. Obstet Gynecol 62:715–719
Rose PG, Stoler MH, Abdul-Karim FW, 1998, Papillary squamotransitional cell carcinoma of the vagina. Int J Gynecol Pathol 17:372–375
Vesoulis Z, Erhardt CA, 2001, Cytologic diagnosis of vaginal papillary squamotransitional cell carcinoma. A case report. Acta Cytol 45:465–469
Gao Z, Bhuiya T, Falkowski O, 2005, Papillary squamotransitional cell carcinoma of the vagina: a case report and review of literature. J Obstet Gynaecol 25:94–96
Kleter B, van Doorn LJ, Schrauwen L, Molijn A, Sastrowijoto S, ter Schegget J, Lindeman J, ter Harmsel B, Burger M, Quint W, 1999, Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol 37:2508–2517
Koenig C, Turnicky RP, Kankam CF, Tavassoli FA, 1997, Papillary squamotransitional cell carcinoma of the cervix: a report of 32 cases. Am J Surg Pathol 21:915–921
Randall ME, Andersen WA, Mills SE, Kim JA, 1986, Papillary squamous cell carcinoma of the uterine cervix: a clinicopathologic study of nine cases. Int J Gynecol Pathol 5:1–10
Urist MJ, Di Como CJ, Lu ML, Charytonowicz E, Verbel D, Crum CP, Ince TA, McKeon FD, Cordon-Cardo C, 2002, Loss of p63 expression is associated with tumor progression in bladder cancer. Am J Pathol 161:1199–1206
Lininger RA, Wistuba I, Gazdar A, Koenig C, Tavassoli FA, Albores-Saavedra J, 1998, Human papillomavirus type 16 is detected in transitional cell carcinomas and squamotransitional cell carcinomas of the cervix and endometrium. Cancer 83:521– 527
Robert ME, Fu YS, 1990, Papillary squamous cell carcinoma of the uterine cervix—a review with emphasis on prognostic factors and unusual variants. Semin Diagn Pathol 7:173– 189
Qizilbash AH, 1974, Papillary squamous tumors of the uterine cervix: a clinical and pathologic study of 21 cases. Am J Clin Pathol 61:508–520
Bass PS, Birch B, Smart C, Theaker JM, Wells M, 1994, Lowgrade transitional cell carcinoma of the vagina—an unusual cause of vaginal bleeding. Histopathology 24(6):581–583
Fetissof F, Haillot O, Lanson Y, Arbeille B, Lansac J, 1990, Papillary tumour of the vagina resembling transitional cell carcinoma. Pathol Res Pract 186(3):358–364
Jendresen MB, Kvist E, Glenthoj A, 1997, Papillary transitional cell tumour in the vagina. Scand J Urol Nephrol 31, 1):107–108
Singer G, Hohl MK, Hering F, Anabitarte M, 1998, Transitional cell carcinoma of the vagina with pagetoid spread pattern. Hum Pathol 29(3):299–301
Tardio JC, Salas C, 2001, Vaginal papillary carcinomas with transitional cell differentiation: a morphological variant of squamous cell carcinoma? Histopathology 39(4):436–438
Mondaini N, Giubilei G, Raspollini MR, Crisci A, Orlando V, 2005, Recurrence of vaginal implantation of transitional cell carcinoma of the urinary tract. Gynecol Oncol 97, 2):669–670
Hermanova M, Vitezslav V, Husicka R, Neumanova R, Pacik D, 2008, Multicentric transitional cell carcinoma of the vagina and the ureter. Ann Diagn Pathol 12(5):365–367
Labonte S, Tetu B, Boucher D, Larue H, 2001, Transitional cell carcinoma of the endometrium associated with a benign ovarian Brenner tumor: a case report. Hum Pathol 32:230–232
Ordonez NG, 2000, Transitional cell carcinomas of the ovary and bladder are immunophenotypically different. Histophatology 36:433–438
Ollayos CW, Lichy J, Duncan BW, Ali IS, 1996, Papillary squamous carcinoma of the uterine cervix: report of case with HPV 16 DNA and brief review. Gynecol Oncol 63:388–391
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 149
EP 153
DI 10.1007/s12253-010-9280-8
PG 5
ER
PT J
AU Ioannidis, O
Papaemmanuil, S
Kakoutis, E
Papadopoulos, G
Chatzopoulos, S
Kotronis, A
Makrantonakis, N
AF Ioannidis, Orestis
Papaemmanuil, Stylliani
Kakoutis, Emmanouil
Papadopoulos, George
Chatzopoulos, Stavros
Kotronis, Anastasios
Makrantonakis, Nikolaos
TI Fibroepithelioma of Pinkus in Continuity with Nodular Basal Cell Carcinoma: Supporting Evidence of the Malignant Nature of the Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal cell carcinoma; Fibroepithelioma of Pinkus; Nodular; Skin cancer; Trichoblastoma
ID Basal cell carcinoma; Fibroepithelioma of Pinkus; Nodular; Skin cancer; Trichoblastoma
AB Basal cell carcinoma, the most common skin cancer, has several clinical and histopathological variants, with its most common form being nodular basal cell carcinoma. Fibrioepithelioma of Pinkus is considered as an unusual variant of basal cell carcinoma by some authors while others consider it to be a benign analogue of basal cell carcinoma. We present a rare case of fibroepithelioma of Pinkus in continuity with a nodular basal cell carcinoma, a finding that supports the classification of fibroepithelioma of Pinkus as a variant of basal cell carcinoma.
C1 [Ioannidis, Orestis] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Papaemmanuil, Stylliani] General Regional Hospital ‘George Papanikolaou’, Department of PathologyThessaloniki, Greece.
[Kakoutis, Emmanouil] General Regional Hospital ‘George Papanikolaou’, First Surgical DepartmentThessaloniki, Greece.
[Papadopoulos, George] General Regional Hospital ‘George Papanikolaou’, First Surgical DepartmentThessaloniki, Greece.
[Chatzopoulos, Stavros] General Regional Hospital ‘George Papanikolaou’, First Surgical DepartmentThessaloniki, Greece.
[Kotronis, Anastasios] General Regional Hospital ‘George Papanikolaou’, First Surgical DepartmentThessaloniki, Greece.
[Makrantonakis, Nikolaos] General Regional Hospital ‘George Papanikolaou’, First Surgical DepartmentThessaloniki, Greece.
RP Ioannidis, O (reprint author), General Regional Hospital ‘George Papanikolaou’, First Surgical Department, 54640 Thessaloniki, Greece.
EM telonakos@hotmail.com
CR Bath-Hextall F, Bong J, Perkins W et al, 2004, Interventions for basal cell carcinoma of the skin: systematic review. BMJ 329:705
Wong CS, Strange RC, Lear JT, 2003, Basal cell carcinoma. BMJ 327:794–8
Crowson AN, 2006, Basal cell carcinoma: biology, morphology and clinical implications. Mod Pathol 19:S127–47
Brooke RC, 2005, Basal cell carcinoma. Clin Med 5:551–4
Misago N, Suzuki Y, Miura Y et al, 2004, Giant polypoid basal cell carcinoma with features of fibroepithelioma of Pinkus and extensive cornification. Eur J Dermatol 14:272–5
Gellin GA, Bender B, 1966, Giant premalignant fibroepithelioma. Arch Dermatol 94:70–3
Pinkus H, 1953, Premalignant fibroepithelial tumors of skin. Arch Dermatol Syphilol 67:598–615
Zalaudek I, Ferrara G, Broganelli P et al, 2006, Dermoscopy patterns of fibroepithelioma of pinkus. Arch Dermatol 142:1318–22
Bowen AR, LeBoit PE, 2005, Fibroepithelioma of pinkus is a fenestrated trichoblastoma. Am J Dermatopathol 27:149–54
Katona TM, Ravis SM, Perkins SM et al, 2007, Expression of androgen receptor by fibroepithelioma of Pinkus: evidence supporting classification as a basal cell carcinoma variant? Am J Dermatopathol 29:7–12
Stern JB, Haupt HM, Smith RR, 1994, Fibroepithelioma of Pinkus: eccrine duct spread of basal cell carcinoma. Am J Dermatopathol 16:585–7
Schulz T, Hartschuh W, 1997, Merkel cells are absent in basal cell carcinomas but frequently found in trichoblastomas. An immunohistochemical study. J Cutan Pathol 24:14–24
Ackerman AB, Gottlieb GJ, 2005, Fibroepithelial tumor of Pinkus is trichoblastic, basal-cell, carcinoma. Am J Dermatopathol 27:155–9
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 155
EP 157
DI 10.1007/s12253-010-9284-4
PG 3
ER
PT J
AU Terada, T
Moriki, T
AF Terada, Tadashi
Moriki, Toshiaki
TI Monolobar Hepatobiliary Fibropolycystic Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caroli’s disease; Polycystic liver; Monolobar disease; Persistent ductal plate; Portal thrombi; Intrahepatic bile duct development
ID Caroli’s disease; Polycystic liver; Monolobar disease; Persistent ductal plate; Portal thrombi; Intrahepatic bile duct development
AB We herein report a case of monolobar hepatobiliary fibropolycystic disease. A 75-year-old woman presented with heartburn. Imaging modalities including US, CT, and MRI revealed marked atrophy and multiple biliary cysts of the hepatic left lobe. The hepatic right lobe was normal. ERCP and bile duct endoscopy revealed anomalous pancreaticobiliary union, choledochal dilation, dilation of left intrahepatic bile ducts, and small choledochal non-invasive adenocarcinoma. Polycystic kidney diseases were absent. The patient underwent pancreatico-duodenectomy and extended hepatic left lobectomy. Grossly, the hepatic left lobe was markedly atrophic, and studded with numerous biliary cysts. The left intrahepatic bile ducts were dilated (Caroli’s disease) and the common bile duct showed type I choledochal dilation. The right hepatic lobe was normal. Histologically, the hepatic left lobe was replaced by fibroelastosis. The intrahepatic bile ducts showed ductal plate malformation such as irregular contours, invaginations, and protrusions. The numerous biliary cysts also showed ductal plate malformation. There were numerous persistent ductal plates and microhamartomas. Many hyalinized destructive biliary cysts and ductal plates were recognized. The liver parenchyma was scant and free of hepatocellular malformations. The portal veins showed old obliterative portal thrombosis. The right hepatic lobe was normal. Immunohistochemically, the biliary cells were positive for cytokeratin 7, 8, 18 and 19, and MUC6 and CD10, but negative for MUC2 and MUC5AC. The biliary cysts, persistent ductal plate, and microhamartomas were positive for fetal apomucin antigen MUC1.
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231, 424-8636 Shizuoka, Japan.
[Moriki, Toshiaki] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231, 424-8636 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 424-8636 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
CR Jorgensen MJ, 1977, The ductal plate malformation. Acta Pathol Microbiol Scand Supple 257:1–87
Desmet VJ, 1992, Congenital disease of intrahepatic bile ducts: variations on the theme “ductal plate malformation”. Hepatology 16:1069–1083
Terada T, Nakanuma Y, Ohta G, 1987, Glandular elements around the intrahepatic bile ducts in man: their morphology and distribution in normal livers. Liver 7:1–8
Terada T, Nakanuma Y, 1995, Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development. Am J Pathol 146:67–74
Terada T, Nakanuma Y, 1993, Development of human intrahepatic peribiliary glands: histological, keratin immunohistochemical and mucus histochemical analyses. Lab Invest 68:261–269
Terada T, Okada Y, Nakanuma Y, 1995, Expression of matrix proteinases during human intrahepatic bile duct development: a possible role in biliary cell migration. Am J Pathol 147:1207–1213
Terada T, Nakanuma Y, 1995, Expression of pancreatic enzymes, α-amylase, trypsinogen and lipase, during human liver development and maturation. Gastroenterology 108:1236–1245
Terada T, Nakanuma Y, 1994, Profiles of expression of carbohydrate chain structures during human intrahepatic bile duct development and maturation: a lectin-histochemical and immunohistochemical study. Hepatology 20:388–397
Terada T, Nakanuma Y, 1994, Expression of tenascin, type IV collagen and laminin during human intrahepatic bile duct development and in intrahepatic cholangiocarcinoma. Histopathology 25: 143–150
Terada T, Ohta T, Nakanuma Y, 1994, Expression of transforming growth factor-α and its receptor during human liver development and maturation. Virchows Archiv 424:669–675
Terada T, Nakanuma Y, Sirica AE, 1998, Immunohistochemical demonstration of MET overexpression in human intrahepatic cholangiocarcinoma and in hepatolithiasis. Hum Pathol 29:175–180
Terada T, Ashida K, Kitamura Y, Matsunaga Y, Takashima K, Kato M, Ohta T, 1998, Expression of E-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development. J Hepatol 28:263–269
Terada T, Kato M, Horie S, Endo K, Kitamura Y, 1998, Expression of pancreatic alpha-amylase protein and messenger RNA on hilar primitive bile ducts and hepatocytes during human fetal liver organogenesis: an immunohistochemical and in situ hybridization study. Liver 18:313–319
Terada T, Ukita Y, Ueyama J, Ohta T, 2000, Protein expression of double-stranded RNA-activated protein kinase, PKR, in intrahepatic bile ducts in normal adult livers, fetal livers, primary biliary cirrhosis, hepatolithiasis and intrahepatic cholangiocarcinoma. Liver 20:450–457
Kato M, Shinozawa T, Kato S, Terada T, 2000, Divergent expression of midkine in the human fetal liver and kidney: an immunohistochemical analysis of developmental changes in hilar primitive bile ducts and hepatocytes. Liver 20:475–481
Kato M, Shinozawa T, Kato S, Terada T, 2004, Immunohistochemical localization of truncated midkine in developing human bile ducts. Histol Histopathol 18:129–134
Sasaki M, Nakanuma Y, Terada T, Kim YS, 1995, Biliary epithelial expression of MUC1, MUC2, MUC3 and MUC5/6 apomucins during intrahepatic bile duct development and maturation. Am J Pathol 147:574–579
Terada T, Nakanuma Y, 1993, Development of human peribiliary capillary plexus: a lectin-histochemical and immunohistochemical study. Hepatology 18:529–536
Terada T, Kitamura Y, Nakanuma Y, 1997, Normal and abnormal development of the intrahepatic biliary system: a review Tohoku. J Exp Med 181:19–32
Summerfield JA, Nagafuchi Y, Sherlock S, Cadafalch J, Scheuer PJ, 1986, Hepatobiliary fibropolycystic disease: a clinical and histological review of 51 patients. J Hepatol 2:141–156
Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y, 2002, Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746
Terada T, Kawaguchi M, 2005, Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med 271:271–275
Terada T, Tanigichi M, 2004, Intraductal oncocytic papillary neoplasm of the liver. Pathol Int 54:116–123
Terada T, 2009, Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Oncol 28:29–34
Terada T, 2008, Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene. World J Gastroenterol 14:7256–7259
Nakanuma Y, Kurumaya H, Ohta G, 1984, Multiple cysts in the hepatic hilum and their pathogenesis: a suggestion of periductal gland origin. Virchows Arch [A] 404:341–350
Wanless IR, Zahradnik J, Heathcote EJ, 1987, Hepatic cysts of periductal gland origin presenting as obstructive jaundice. Gastroenterology 93:89
Terada T, Nakanuma Y, 1990, Pathological observations of intrahepatic peribiliary glands in 1000 consecutive autopsy livers: III. Survey of necroinflammation and cystic dilatation Hepatology 12:1229–1233
Kida T, Nakanuma Y, Terada T, 1992, Cystic dilatation of peribiliary glands in livers with adult polycystic disease and livers with solitary non-parasitic cysts: an autopsy study. Hepatology 16:334–340
Terada T, Minato H, Nakanuma Y, ShinozakiK,Kobayashi S,Matsui O, 1992, Ultrasound visualization of hepatic peribiliary cysts: a comparison with morphology. Am J Gastroenterol 87:1499–1502
Itai Y, Ebihara R, Tohno E, Tsunoda HS, Kurosaki Y, Saida Y, Doy M, 1994, Hepatic peribiliary cysts: multiple tiny cysts within the larger portal tract, hepatic hilum, or both. Radiology 191:107–110
Terada T, Nakanuma Y, 1988, Congenital biliary dilatation in autosomal dominant adult polycystic disease of the liver and kidneys. Arch Pathol Lab Med 112:1113–1116
Terada T, Matsushita H, Tashiro J, Sairenji T, Erigichi M, Osada I, 2003, Cholesterol hepatolithiasis with peribiliary cysts. Pathol Int 53:716–720
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Terada T, Ishida F, Nakanuma Y, 1989, Vascular plexus around intrahepatic bile ducts in normal livers and portal hypertension. J Hepatol 8:139–149
Terada T, Hoso M, Nakanuma Y, 1989, Microvasculature in the small portal tracts in idiopathic portal hypertension: a morphological comparison with other hepatic diseases. Virchows Arch [A] 415:61–68
Terada T, Nakanuma Y, Hoso M, Obata H, 1991, Expression of HLA-DR antigen on hepatic vascular endothelial cells in idiopathic portal hypertension. Clin Exp Immunol 84:303–307
Terada T, Nakanuma Y, Obata H, 1991, HLA-DR expression on the microvasculature in portal tracts in idiopathic portal hypertension: immunohistochemical characteristics and relation to portal phlebosclerosis. Arch Pathol Lab Med 115:993–997
Van Eyken P, Sciot R, Callea F, Van der Steen K, Moerman P, Desmet VJ, 1988, The development of the intrahepatic bile ducts in man: a keratin immunohistochemical study. Hepatology 8:1589–1595
Awasthi A, Das A, Srinivasan R, Joshi K, 2004, Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver. Histopathology 45:260–267
Furukawa T, Kloppel G, Volkan Adsay N et al, 2005, Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch 447:794–799
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Young WT, Thomas GV, Blethyn AJ, Lawrie BW, 1992, Choledochal cysts and congenital anomalies of the pancreaticobiliary junction: the clinical findings, radiology and outcome in nine cases. Br J Radiol 65:33–38
Misra SP, Dwivedi M, 1990, Pancreaticobiliary ductal union. Gut 1144–1149
Noun R, Sayegh R, Tohme-Noun C, Honein K, Smayra T, Aoun N, 2006, Extracystic biliary carcinoma associated with anomalous psancreaticobiliary junction and cysts. J Hepatobiliary Pancreat Surg 13:557–559
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 159
EP 165
DI 10.1007/s12253-010-9285-3
PG 7
ER
PT J
AU Terada, T
AF Terada, Tadashi
TI Solitary Plasmacytoma of the Thracic Vertebra Presenting with Sudden Paraplegia and Back Pain: A Pathologic Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Plasmacytoma; Vertebra; Bone; Immunohistology; Histopathology
ID Plasmacytoma; Vertebra; Bone; Immunohistology; Histopathology
AB Solitary plasmacytoma (SPC) accounts for 5% of plasma cell neoplasm. SPC of the spine is relatively rare, and SPC presenting with sudden paraplegia is very rare. A 53 year-old woman was admitted to our hospital complaining of sudden severe paraplegia and back pain. Emergency MRI revealed a tumor of the thoracic vertebra no. 10 (Th10). Pressure fracture of the Th10 was also recognized. The tumor was not osteolytic and invasion was recognized around the Th10. The tumor directly compressed the spinal cord. An excision of the tumor was performed under the clinical diagnosis of metastatic carcinoma. Pathologtically, the tumor consisted of plasmacytoid atypical cells with hyperchromatic nuclei. Histochemically, the tumor cells showed pyroninophilia. Immunohistochemically, the tumor cells were positive for λ-light chain, but negative for cytokeratin, epithelial mermbrane antigen, vimentin, CD45, CD20, CD45RO, κ-light chain, α-heavy chain, λ-heavy chain, μ-heavy chain, δ-heavy chain, ε-heavy chain, IgA, IgG, IgM, synaptophysin, chromogranin, S100 protein, desmin, α-smooth muscle antigen, myoglobin, and p53 protein. The Ki-67 labeling was 73%. The author diagnosed the tumor as SPC with λ-light chain disease. After the diagnosis, whole body CT and MRI revealed no other tumors. Blood and serum test revealed no significant changes; no M-protein was recognized. However, voided urine test revealed λ-light chain protein. The patient underwent fixation operation of TH10, and received radiation (50 Gray) and chemotherapy. No recurrence or transformation into myeloma occurred at the present time 25 months after the first manifestation. The present study indicated that pathological examination is an only clue to the diagnosis of SPC of the vertebra bone.
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231 Shimizu-Ku, 424-8636 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 424-8636 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
CR Grogan TM, Muller-Hermelink HK, Van Camp B, Harris NL, Kyle RA, 2001, Plasm cell neoplasms. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds, World health organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 142–156
Bacci G, Savini R, Calderoni P, Gnudi S, Minutllo A, Picci P, 1982, Solitary plasmacytoma of the vertebral column: a report of 15 cases. Tumori 30:271–275
Poor MM, Hitchon PW, Riggs CE, 1988, Solitary spinal plasmacytoma: management and outcome. J Spinal Disord 1:295–300
Colak A, Cataltepe O, Ozgen T, Erbengi A, 1989, Spinal cord compression caused by plasmacytoma: a retrospective review of 14 cases. Neurosurg Rev 12:305–308
Frassica DA, Fraqssica FJ, Schray MF, Sim FH, Kyle RA, 1989, Solitary plasmcytoma of bone: mayo clinic experience. Int J Radiat Oncol Biol Phys 16:43–48
McLain RF, Weinstein JN, 1989, Solitary plasmacytoma of the spine: a review of 84 cases. J Spiral Disord 2:69–74
Liebross RH, Ha CS, Cox JD, Weber D, Delasalle K, Alexanian R, 1998, Solitary bone plasmacytoma: outcome and prognostic factors after radiotherapy. Int J Radiat Oncol Biol Phys 41:1063–1067
Baba H, Maezawa Y, Furusawa N, Wada M, Kokuba Y, Imura S, Imamura Y, Yamada Y, 1998, Solitary plasmcytoma of the spine associated with neurological complications. Spinal Cord 36:470– 475
Dave BR, Nanda A, Anandjiwala JV, 2009, Transpedicular percutaneous biopsy of vertebral body lesions: a case series of 71 cases. Spinal Cord 47:384–389
Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura RY, 2002, Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746
Terada T, Kawaguchi M, 2005, Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med 206:271–275
Terada T, Taniguchi M, 2004, Intraductal oncocytic papillary neoplasm of the liver. Pathol Int 54:116–123
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 167
EP 169
DI 10.1007/s12253-010-9292-4
PG 3
ER
PT J
AU Fukuyama, A
Yokoyama, Y
Futagami, M
Shigeto, T
Wada, R
Mizunuma, H
AF Fukuyama, Asami
Yokoyama, Yoshihito
Futagami, Masayuki
Shigeto, Tatsuhiko
Wada, Ryuichi
Mizunuma, Hideki
TI A Case of Uterine Leiomyoma with Intravenous Leiomyomatosis—Histological Investigation of the Pathological Condition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE CD-34 antibody. Immunostaining; Intravenous leiomyomatosis; Pathological genesis; Uterine leiomyoma
ID CD-34 antibody. Immunostaining; Intravenous leiomyomatosis; Pathological genesis; Uterine leiomyoma
AB Intravenous leiomyomatosis (IVL) is generally defined as a histologically benign leiomyoma derived from a uterine myoma or intrauterine venous wall that has grown and extended intravenously. We here report on a single case of IVL, and investigate its pathological genesis. Regarding the part of the myoma extending to the vessel lumen, observations found the myoma to be pushing into the vessel. Immunostaining with CD34 antibody gave an image of the area where the myoma pushed into the vessel, showing CD34-positive vessel endothelium cells folded back into a layer covering the myoma, and continuing to line of the surface of the myoma within the vessel. Early pathological genesis of IVL was clarified for the first time that the tumor did not invade the vessel by breaking the venous wall, but rather advanced by stretching the vascular wall and progressing into the vein like a polyp, covered in endothelium cells.
C1 [Fukuyama, Asami] Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
[Yokoyama, Yoshihito] Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
[Futagami, Masayuki] Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
[Shigeto, Tatsuhiko] Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
[Wada, Ryuichi] Hirosaki University Graduate School of Medicine, Department of Pathology and Molecular Medicine, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
[Mizunuma, Hideki] Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 5-Zaifu-cho, Hirosaki, 036-8562 Aomori, Japan.
RP Yokoyama, Y (reprint author), Hirosaki University Graduate School of Medicine, Department of Obstetrics and Gynecology, 036-8562 Aomori, Japan.
EM yokoyama@cc.hirosaki-u.ac.jp
CR Norris HJ, Parmley T, 1975, Mesenchymal tumors of the uterus. Intravenous leiomyomatosis. A clinical and pathologic study of 14 cases. Cancer 36:2146–2178
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Mitsuhashi A, Nagai Y, Sugita M et al, 1999, GnRH agonist for intravenous leiomyomatosis eith cardiac extension. A case report. J Reprod Med 44:883–886
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 171
EP 174
DI 10.1007/s12253-010-9265-7
PG 4
ER
PT J
AU Stojsic, J
Stevic, R
Kontic, M
Stojsic, Z
Drndarevic, N
Bunjevacki, V
Jekic, B
AF Stojsic, Jelena
Stevic, Ruza
Kontic, Milica
Stojsic, Zorica
Drndarevic, Neda
Bunjevacki, Vera
Jekic, Biljana
TI Large Cell Lung Carcinoma with Unusual Imaging Feature, Immunophenotype and Genetic Finding
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Large cell lung carcinoma; Immunophenotype; Imaging; Tumor genetic; Diagnosis
ID Large cell lung carcinoma; Immunophenotype; Imaging; Tumor genetic; Diagnosis
AB We present a case of large cell lung carcinoma in sixty-one year old male with typical lung cancer symptoms but unusual radiological presentation and immunophenotype. Tumor morphological finding related to its radiological finding was suggestive for large cell lymphoma or carcinoma, but its immunophenotype made confusion for pathological diagnosis. No p53 mutations were detected in genetic investigation. Multidisciplinar diagnostic approach to some tumors is useful for their final diagnosis.
C1 [Stojsic, Jelena] Clinical Centre of Serbia, Institute for Lung Diseases and TuberculosisBelgrade, Serbia.
[Stevic, Ruza] Clinical Centre of Serbia, Institute of RadiologyBelgrade, Serbia.
[Kontic, Milica] Clinical Centre of Serbia, Institute for Lung Diseases and TuberculosisBelgrade, Serbia.
[Stojsic, Zorica] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Drndarevic, Neda] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Bunjevacki, Vera] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Jekic, Biljana] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
RP Stojsic, J (reprint author), Clinical Centre of Serbia, Institute for Lung Diseases and Tuberculosis, Belgrade, Serbia.
EM dr.jelenastoj@sezampro.rs
CR Byrd RB, Carr DT, Miller WE, Payne WS, Woolen LB, 1968, Radiographic abnormalities in carcinoma of the lung as related to histological cell type. Thorax 24:573–575
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Faggiano A, Sabourin J-C, Lumbroso J, Duvillard P, Leboulleux S, Dromain C, Colao A, Schlumberger M, Baudin E, 2007, Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas.Diagnostic and prognostic features. Cancer 110(2):265–274
Maddau C, Confortini M, Bisanzi S, Janni A, Montinaro F, Paci E, Pontenani G, Rulli P, Salani A, Zappa M, Benvenuti A, Carozzi FM, 2006, Prognostic significance of p53 and Ki-67 antigen expression in surgically treated non-small cell lung cancer. Immunocytochemical detection with imprint cytology. Am J Clin Pathol 125:425–431
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Takahashi T, Munakata M, Ohtsuka Y, 2002, Expression and alteration of Ras and P53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis. Cancer 95(3):624– 633
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2011
VL 17
IS 1
BP 175
EP 179
DI 10.1007/s12253-010-9272-8
PG 5
ER
PT J
AU Zaravinos, A
Chatziioannou, M
Lambrou, IG
Boulalas, I
Delakas, D
Spandidos, AD
AF Zaravinos, Apostolos
Chatziioannou, Maria
Lambrou, I George
Boulalas, Ioannis
Delakas, Dimitris
Spandidos, A Demetrios
TI Implication of RAF and RKIP Genes in Urinary Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RAF family genes; RKIP; Microarrays; qPCR; Computational analysis; Transitional cell carcinoma of the urinary bladder
ID RAF family genes; RKIP; Microarrays; qPCR; Computational analysis; Transitional cell carcinoma of the urinary bladder
AB RKIP has been shown to regulate the RAS-RAFMEK-ERK kinase cascade acting as modulator of apoptosis and metastasis in prostate cancer. Our goal was to examine the expression of the RAF (A-RAF, B-RAF and RAF-1) and RKIP genes in urinary bladder cancer. Microarray analysis and qPCR was employed to investigate the expression of RAF and RKIP, in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder vs. the corresponding levels of adjacent normal tissue. Computational analysis was also performed on Gene Expression Omnibus (GEO) datasets, to unravel differences in the expression of RAF or RKIP between tumor and control samples, and between superficial and muscle invasive tumors. Microarray analysis revealed >2-fold expression of BRAF and RKIP in T2, T3, grade III tumors vs. controls. B-RAF over-expression was verified by qPCR in pT1, grade III tumors vs. their normal counterparts (p=0.016). qPCR revealed a significant RKIP reduction in TCC vs. normal tissue (p=0.002 and p<0.001 for T1, grade II and Ta-T1, grade III, respectively); All RAF genes were positively correlated among each other (A-RAF/B-RAF, p=0.003; A-RAF/RAF-1, p<0.001; B-RAF/RAF-1, p=0.050), whereas B-RAF was negatively correlated with RKIP in TCC (p=0.050). Further computational analysis revealed different expression profiles for the genes of interest, among muscle invasive carcinomas, superficial TCCs, cystectomy specimens and normal tissue. The reduced RKIP mRNA levels in TCC and the elevated levels of B-RAF in pT1, grade III tumors vs. normal tissue, corroborate that these genes are involved in the pathogenesis of urinary bladder cancer.
C1 [Zaravinos, Apostolos] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
[Chatziioannou, Maria] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
[Lambrou, I George] University of Athens, 1st Department of Pediatrics, Goudi, 11527 Athens, Greece.
[Boulalas, Ioannis] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
[Delakas, Dimitris] Department of Urology, VoulaAthens, Greece.
[Spandidos, A Demetrios] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
RP Spandidos, AD (reprint author), University of Crete, Medical School, Department of Virology, 71110 Heraklion, Greece.
EM spandidos@spandidos.gr
CR Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics. CA Cancer J Clin 58:71–96
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Boulalas I, Zaravinos A, Karyotis I, Delakas D, Spandidos DA, 2009, Activation of RAS family genes in urothelial carcinoma. J Urol 181:2312–2319
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Boulalas I, Zaravinos A, Delakas D, Spandidos DA, 2009, Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder. Int J Biol Markers 24:17–21
Zaravinos A, Kanellou P, Baritaki S, Bonavida B, Spandidos DA, 2009, BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell Cycle 8:1402–1408
Zaravinos A, Bizakis J, Spandidos DA, 2008, RKIP and BRAF aberrations in human nasal polyps and the adjacent turbinate mucosae. Cancer Lett 264:288–298
Gattenlohner S, Etschmann B, Riedmiller H, Muller-Hermelink HK, 2009, Lack of KRAS and BRAF mutation in renal cell carcinoma. Eur Urol 55:1490–1491
Karlou M, Saetta AA, Korkolopoulou P et al, 2009, Activation of extracellular regulated kinases, ERK1/2, predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations. Pathology 41:327–334
Mhawech-Fauceglia P, Fischer G, Beck A, Cheney RT, Herrmann FR, 2006, Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up. Eur J Surg Oncol 32:439–444
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Chatterjee D, Bai Y, Wang Z et al, 2004, RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem 279:17515–17523
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 181
EP 190
DI 10.1007/s12253-010-9295-1
PG 10
ER
PT J
AU Guzman, G
Chennuri, R
Voros, A
Boumendjel, R
Locante, A
Patel, R
Valyi-Nagy, T
AF Guzman, Grace
Chennuri, Rohini
Voros, Andras
Boumendjel, Redouane
Locante, Alberto
Patel, Roshan
Valyi-Nagy, Tibor
TI Nucleometric Study of Anisonucleosis, Diabetes and Oxidative Damage in Liver Biopsies of Orthotopic Liver Transplant Recipients with Chronic Hepatitis C Virus Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diabetes; Hepatitis C virus (HCV); Hepatocyte anisonucleosis; Image analysis; Nucleometry; Oxidative damage; 8-hydroxy-2′deoxyguanosine (8-OHdG) immunomarker
ID Diabetes; Hepatitis C virus (HCV); Hepatocyte anisonucleosis; Image analysis; Nucleometry; Oxidative damage; 8-hydroxy-2′deoxyguanosine (8-OHdG) immunomarker
AB Anisonucleosis is defined as a morphological manifestation of nuclear injury characterized by variation in the size of the cell nuclei. It has been described in variety of benign conditions and is most pronounced in dysplasia and malignancy. To better understand the pathogenesis of anisonucleosis in liver diseases, this study focused on hepatocyte anisonucleosis in biopsies of liver transplant recipients who developed recurrent chronic hepatitis C virus (HCV) infection. Post transplant surveillance liver biopsy specimens were evaluated employing light microscopy, immunohistochemistry, digital image analysis, and nucleometry for histopathological analyses, measurement of nuclear size, and quantification of tissue expression of oxidative marker 8-hydroxy-2′deoxyguanosine (8-OHdG). Our aim in this study was to determine whether there were any independent associations between hepatocyte anisonucleosis and various clinicopathological parameters. These features included patient age, body mass index, gender, race, donor age, live versus cadaveric donor status, history of diabetes mellitus, history of tacrolimus and cyclosporine therapy, duration post transplant and parameters of hepatitis activity index, fibrosis index, steatosis, and oxidative tissue damage in formalin fixed paraffin embedded (FFPE) liver biopsies as determined by immunohistochemistry using 8-OHdG, an indicator of hydroxyl radical mediated tissue damage. Our findings suggested that in liver transplant recipients with recurrent chronic HCV infection, hepatocyte anisonucleosis is more pronounced in individuals with diabetes mellitus (p=0.0016), and among those who have heightened hepatic expression of the oxidative damage marker 8-OHdG (p=0.0053). Further studies are necessary to determine whether anisonucleosis is an independent marker for diabetes or oxidative damage.
C1 [Guzman, Grace] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Chennuri, Rohini] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Voros, Andras] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Boumendjel, Redouane] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Locante, Alberto] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Patel, Roshan] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
[Valyi-Nagy, Tibor] University of Illinois at Chicago, College of Medicine, Department of Pathology, Room 130, 840 South Wood Street, M/C 847, 60612 Chicago, IL, USA.
RP Guzman, G (reprint author), University of Illinois at Chicago, College of Medicine, Department of Pathology, 60612 Chicago, USA.
EM GraceGuz@uic.edu
CR Crawford Jm, 2004, The liver and biliary tree. Kumar VFN, Abbas A, eds). Philadelphia, WB Saunders, pp 877–937
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Kuo SH, Lai MY, Liu YR, Lee YT, Chen DS, Lee CS, Hsu HC, 1994, Nuclear area and DNA content in tumor and nontumor portions of hepatocellular carcinoma. Anal Quant Cytol Histol 16:153–158
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 191
EP 199
DI 10.1007/s12253-010-9296-0
PG 9
ER
PT J
AU Lee, JH
Ryu, TY
Cho, ChH
Kim, DK
AF Lee, Jae-Ho
Ryu, Tae-Yung
Cho, Chi-Heum
Kim, Dae-Kwang
TI Different Characteristics of Mitochondrial Microsatellite Instability Between Uterine Leiomyomas and Leiomyosarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Genetic instability; Mitochondrial microsatellite instability; Uterine leiomyoma; Uterine leiomyosarcomas
ID Genetic instability; Mitochondrial microsatellite instability; Uterine leiomyoma; Uterine leiomyosarcomas
AB Uterine leiomyomas are benign tumors of the uterus that arise clonally from smooth muscle cells of the myometrium and are the most common reason for hysterectomies. The aim of this study was to evaluate mitochondrial microsatellite instability (mtMSI) in uterine leiomyomas and leiomyosarcomas to clarify the molecular pathogenetic distinction between these tumors. DNA was isolated from paired normal and tumoral tissues in 50 patients with uterine leiomyomas and 14 patients with leiomyosarcomas. mtMSI was analyzed by using eight microsatellite markers. Our result showed that mitochondrial microsatellite instability was not found in all uterine leiomyomas. However, 3 (21.4%) of 14 patients with leiomyosarcomas had mtMSI and the frequencies of mtMSI in these tumors were significantly different (p<0.01). Distinctive characteristics of mitochondrial genetic instability in uterine leiomyomas and leiomyosarcomas suggested the potential of mtMSI as a marker for differential diagnosis between them.
C1 [Lee, Jae-Ho] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Ryu, Tae-Yung] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Cho, Chi-Heum] Keimyung University, School of Medicine, Department of Obstetrics and GynecologyDaegu, South Korea.
[Kim, Dae-Kwang] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
RP Kim, DK (reprint author), Keimyung University, School of Medicine, Department of Anatomy, 2800 Daegu, South Korea.
EM dkkimmd@kmu.ac.kr
CR Cramer SF, Patel A, 1990, The frequency of uterine leiomyomas. Am J Clin Pathol 94:435–438
Parker WH, 2007, Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril 87:725–736
Walker CL, Stewart EA, 2005, Uterine fibroids: the elephant in the room. Science 308:1589–1592
Chen L, Yang B, 2008, Immunohistochemical analysis of p16, p53, and Ki-67 expression in uterine smooth muscle tumors. Int J Gynecol Pathol 27:326–332
Packenham JP, du Manoir S, Schrock E et al, 1997, Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization. Mol Carcinog 19:273–279
Thibodeau S, Bren G, Schaid D, 1993, Microsatellite instability in cancer of the proximal colon. Science 75:1027–1038
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Boland CR, Thibodeau SN, Hamilton SR et al, 1998, A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257
Naidoo R, Chetty R, 1998, The application of microsatellites in molecular pathology. Pathol Oncol Res 4:310–315
Quade BJ, Pinto AP, Howard DR et al, 1999, Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in contrast to leiomyoma. Am J Pathol 154:945–950
Suwa K, Ohmori M, Miki H, 1999, Microsatellite alterations in various sarcomas in Japanese patients. J Orthop Sci 4:223–230
Amant F, Dorfling CM, Dreyer L et al, 2001, Microsatellite instability in uterine sarcomas. Int J Gynecol Cancer 11:218– 223
Howell N, Kubacka I, Mackey DA, 1996, How rapidly does the humanmitochondrial genome evolve?AmJ HumGenet 59:501–509
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Mittal KR, Chen F, Wei JJ et al, 2009, Molecular and immunohistochemical evidence for the origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leiomyoma-like areas. Mod Pathol 22:1303–1311
French D, Cermele C, Lombardi AM et al, 1998, Microsatellite alterations in uterine leiomyomas. Anticancer Res 18:349–352
Risinger JI, Umar A, Boyer JC et al, 1995, Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity. Cancer Res 55:5664–5669
Stoneking M, 2000, Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet 67:1029–1032
Lievre A, Chapusot C, Bouvier AM et al, 2005, Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol 23:3517–3525
Lee HC, Yin PH, Lin JC et al, 2005, Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci 104:109–122
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 201
EP 205
DI 10.1007/s12253-010-9297-z
PG 5
ER
PT J
AU Kovacs,
Toth, L
Glavak, Cs
Lakosi, F
Hadjiev, J
Bajzik, G
Vandulek, Cs
Repa, I
AF Kovacs, Arpad
Toth, Lilla
Glavak, Csaba
Lakosi, Ferenc
Hadjiev, Janaki
Bajzik, Gabor
Vandulek, Csaba
Repa, Imre
TI Integrating Functional MRI Information into Radiotherapy Planning of CNS Tumors-Early Experiences
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CNS tumor; fMRI; Radiotherapy
ID CNS tumor; fMRI; Radiotherapy
AB The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR’s in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).
C1 [Kovacs, Arpad] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Toth, Lilla] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Glavak, Csaba] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Lakosi, Ferenc] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Hadjiev, Janaki] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Bajzik, Gabor] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Vandulek, Csaba] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
[Repa, Imre] Kaposvar University, Department of Radiation Oncology, Guba S Street 40, 7400 Kaposvar, Hungary.
RP Kovacs, (reprint author), Kaposvar University, Department of Radiation Oncology, 7400 Kaposvar, Hungary.
EM kovacs.arpad@sic.hu
CR Alvarez R, Liney G, Beavis A, 2006, Repeatability of Functional MRI for Conformal Avoidance Radiotherapy Planning. J Magn Reson Imaging 23:108–114
Aoyama H, Kamada K, Shirato H et al, 2004, Integration of mfunctional brain information into stereotactic irradiation treatment planning using magnetoencephalography and magnetic resonance axonography. Int J Radiat Oncol Biol Phys 58:1177–1183
Bleehen NM, Stenning SP, 1991, A medical research council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer 64:769–774
Burman C, Kutcher GJ, Emami B, Goitein M, 1991, Fitting of tissue tolerance data to analytic function: improving the therapeutic ratio. Int J Radiat Oncol Biol Phys 21:123–135
Chang J, Kowalski A, Hou B, Narayana A, 2008, Feasibility Study of Intensity-Modulated Radiotherapy, IMRT, treatment planning using brain functional MRI. Med Dosim 33(1):42–47
Clark BG et al, 1998, The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy. Int J Radiat Oncol Biol Phys 40:667–675
Emami B et al, 1991, Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122
Flickinger JC, Kondziolka D, Lunsford LD et al, 2000, Development of a model to predict permanent symptomatic postradiosurgery. Int J Radiat Oncol Biol Phys 46:1143–1148
Jemal A, Murray T, Ward E et al, 2005, Cancer statistics, 2005. CA Cancer J Clin 55:10–30
Lee SW, Fraass BA, Marsh LH et al, 1999, Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys 43:79–88
Liu WC, Schulder M, Narra V et al, 2000, Functional magnetic resonance imaging aided radiation treatment planning. Med Phys 27:1563–1572
Marks JE et al, 1980, Cerebral radionecrosis: incidence and risk in relation to dose, time fractionation and volume. Int J Radiat Oncol Biol Phys 7:243–252
Moonen CTW, Bandettini PA, eds,, 1999, Functional MRI1. Springer-Verlag, Berlin
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Teh BS, Mai WY, Grant WH et al, 2002, Intensity modulated radiotherapy, IMRT, decreases treatment-related morbidity and potentially enhances tumor control. Cancer Invest 20:437–451
Voges J, Treuer H, Sturm V et al, 1996, Risk analysis of linear radiosurgery. Int J Radiat Oncol Biol Phys 36:1055–1063
Walker MD, Alexander E, Hunt WE et al, 1978, Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49:333–343
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 207
EP 217
DI 10.1007/s12253-010-9298-y
PG 11
ER
PT J
AU Boonmars, Th
Wu, Z
Boonjaruspinyo, S
Puapairoj, A
Kaewsamut, B
Nagano, I
Pinlaor, S
Yongvanit, P
Wonkchalee, O
Juasook, A
Sudsarn, P
Srisawangwong, T
AF Boonmars, Thidarut
Wu, Zhiliang
Boonjaruspinyo, Sirintip
Puapairoj, Anucha
Kaewsamut, Butsara
Nagano, Isao
Pinlaor, Somchai
Yongvanit, Puangrat
Wonkchalee, Orasa
Juasook, Amornrat
Sudsarn, Pakkayanee
Srisawangwong, Tuanchai
TI Involvement of c-Ski Oncoprotein in Carcinogenesis of Cholangiocacinoma Induced by Opisthorchis viverrini and N-nitrosodimethylamine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Opisthorchiasis; Opisthorchis viverrini; c-Ski; TGF-β; CCA; Carcinogenesis
ID Opisthorchiasis; Opisthorchis viverrini; c-Ski; TGF-β; CCA; Carcinogenesis
AB Opisthorchiasis is the major public health problem in the endemic areas of Thailand and Laos because Opisthorchis viverrini infection causes serious hepatobiliary diseases including CCA. The molecular mechanism of the CCA carcinogenesis induced by the infection remains obscure. To reveal the potential genes and signaling pathways to involve in the carcinogenesis, the present study investigated the expression of c-Ski, an oncogene, and two TGF-β signaling pathway relative genes, TGF-β and Smad4, during the development of CCA induced by O. viverrini infection in hamster model, and in human opisthorchiasis associated CCA. The results showed that the expression of c-Ski gene was greatly up-regulated during the carcinogenesis of CCA in hamster model. The overexpression of c-Ski was confirmed by immunohistological staining result which showed the increased expression of c-Ski protein in cytoplasm of the epithelial lining of hepatic bile ducts. Moreover, the immunohistological staining of the specimens of human opisthorchiasis associated CCA revealed the up-regulated expression of c-Ski and Smad4 proteins in the cytoplasm of the epithelial lining of hepatic bile ducts and stomal fibrosis respectively. The expression of TGF-β and Smad4 were up-regulated, which expression kinetics was time-dependent of CCA development. These results suggest that c-Ski is likely involved in the carcinogenesis of CCA induced by O. viverrini infection through regulating TGF-β signaling pathway.
C1 [Boonmars, Thidarut] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Wu, Zhiliang] Gifu University, Graduate School of Medicine, Department of Parasitology, Yanagido1-1, 501-1194 Gifu, Japan.
[Boonjaruspinyo, Sirintip] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Puapairoj, Anucha] Khon Kaen University, Faculty of Medicine, Department of Pathology, 40002 Khon Kaen, Thailand.
[Kaewsamut, Butsara] Khon Kaen University, Northeast Laboratory Animal Center, 40002 Khon Kaen, Thailand.
[Nagano, Isao] Gifu University, Graduate School of Medicine, Department of Parasitology, Yanagido1-1, 501-1194 Gifu, Japan.
[Pinlaor, Somchai] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Yongvanit, Puangrat] Khon Kaen University, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Wonkchalee, Orasa] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Juasook, Amornrat] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Sudsarn, Pakkayanee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Srisawangwong, Tuanchai] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
RP Boonmars, Th (reprint author), Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
EM bthida@kku.ac.th
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 219
EP 227
DI 10.1007/s12253-010-9300-8
PG 9
ER
PT J
AU Tatrai, E
Hartyanszky, I
Laszik, A
Acsady, Gy
Sotonyi, P
Hubay, M
AF Tatrai, Eniko
Hartyanszky, Istvan
Laszik, Andras
Acsady, Gyorgy
Sotonyi, Peter
Hubay, Marta
TI The Role of Viral Infections in the Development of Dilated Cardiomyopathy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cardiomyopathy; Endomyocardial biopsy; Myocardium; Polymerase chain reaction; Viruses
ID Cardiomyopathy; Endomyocardial biopsy; Myocardium; Polymerase chain reaction; Viruses
AB Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.
C1 [Tatrai, Eniko] Semmelweis University, Department of Forensic & Insurance Medicine, 93 Ulloi str, 1091 Budapest, Hungary.
[Hartyanszky, Istvan] Semmelweis University, Department of Cardiovascular Surgery, 1122 Budapest, Hungary.
[Laszik, Andras] Semmelweis University, Department of Forensic & Insurance Medicine, 93 Ulloi str, 1091 Budapest, Hungary.
[Acsady, Gyorgy] Semmelweis University, Department of Cardiovascular Surgery, 1122 Budapest, Hungary.
[Sotonyi, Peter] Semmelweis University, Department of Forensic & Insurance Medicine, 93 Ulloi str, 1091 Budapest, Hungary.
[Hubay, Marta] Semmelweis University, Department of Forensic & Insurance Medicine, 93 Ulloi str, 1091 Budapest, Hungary.
RP Tatrai, E (reprint author), Semmelweis University, Department of Forensic & Insurance Medicine, 1091 Budapest, Hungary.
EM tatraie@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 229
EP 235
DI 10.1007/s12253-010-9302-6
PG 7
ER
PT J
AU Zhang, B
Feng, X
Wang, J
Xu, X
Lin, N
Liu, H
AF Zhang, Biao
Feng, Xuequan
Wang, Jinhuan
Xu, Xinnu
Lin, Na
Liu, Hongsheng
TI Combined Antitumor Effect of Ad-bFGF-siRNA and Ad-Vpr on the Growth of Xenograft Glioma in Nude Mouse Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE siRNA; bFGF; Vpr; Adenoviral vector
ID siRNA; bFGF; Vpr; Adenoviral vector
AB Basic fibroblast growth factor (bFGF) has been demonstrated to correlate with glioma grade and clinical outcome and has established its possible usefulness as a target for glioma therapy. Vpr has been described as an antitumor agent and displays a potent antitumor nature. Here, we try to investigate whether a combined treatment with bFGF-siRNA and Vpr gene would have a enhanced effectiveness on glioma in vitro and in vivo.After treatments with only Ad-bFGF-siRNA, only Ad-Vpr, and a combination of both, we assessed the changes in cell proliferation, cell cycle, and apoptosis in vitro by the methods of MTT, PI and FITC-AnnexinV double staining, respevtively. In addition, we also evaluated the combined effect of bFGF-siRNA and Vpr gene therapy on glioma in vivo using xenograft glioma models in nude mice. Combined Ad-bFGF-siRNA and Ad-Vpr treatment was more better successful in inhibiting cell proliferation in comparison with treatments of either Ad-bFGF-siRNA or Ad-Vpr alone. Treatment of Ad-Vpr alone or a treatment of a combination of Ad-bFGF-siRNA and Ad-Vpr induced the G2/M cell cycle arrest and apoptosis; however, combined treatment was more effective than the Ad-Vpr treatment alone. Although each single treatment can slow the growth of xenograft glioma, the combined treatment with AdbFGF-siRNA and Ad-Vpr was better than either the AdbFGF-siRNA or Ad-Vpr treatment alone. Our results suggest that the combination therapy with bFGF-siRNA and Vpr gene can achieve a enhanced activity of antiglioma, supporting the idea that the combination of these two antitumor agents could open new perspectives in glioma therapy.
C1 [Zhang, Biao] Tianjin Huan Hu Hospital, Clinical Lab, 300060 Tianjin, China.
[Feng, Xuequan] Tianjin Medical University General Hospital, Department of Neurosurgery, 300192 Tianjin, China.
[Wang, Jinhuan] Tianjin Medical University General Hospital, Department of Neurosurgery, 122# Qixiangtai Road, Hexi District, 300060 Tianjin, China.
[Xu, Xinnu] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 300192 Tianjin, China.
[Lin, Na] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 300192 Tianjin, China.
[Liu, Hongsheng] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 300192 Tianjin, China.
RP Wang, J (reprint author), Tianjin Medical University General Hospital, Department of Neurosurgery, 300060 Tianjin, China.
EM wangjinhuanfch@yahoo.com.cn
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Marek L, Ware KE, Fritzsche A, Hercule P, Helton WR, Smith JE, McDermott LA, Coldren CD, Nemenoff RA, Merrick DT, Helfrich BA, Bunn PA Jr, Heasley LE, 2009, Fibroblast growth factor, FGF, and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells. Mol Pharmacol 75(1):196–207
Wang SJ, Wang JH, Zhang YW, Xu XN, Liu HS, 2008, Effects of small interfering RNA targeting basic fibroblast growth factor on proliferation and apoptosis of glioma cell line U251. Ai Zheng 27, 9):905–909
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 237
EP 242
DI 10.1007/s12253-010-9303-5
PG 6
ER
PT J
AU Mitrovic, Z
Ilic, I
Aurer, I
Kinda, BS
Radman, I
Dotlic, S
Ajdukovic, R
Labar, B
AF Mitrovic, Zdravko
Ilic, Ivana
Aurer, Igor
Kinda, Basic Sandra
Radman, Ivo
Dotlic, Snjezana
Ajdukovic, Radmila
Labar, Boris
TI Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-Hodgkin’s lymphoma; Diffuse large B-cell lymphoma; Survivin; Caspase-3; Prognostic factors; Rituximab; Immunohistochemistry
ID Non-Hodgkin’s lymphoma; Diffuse large B-cell lymphoma; Survivin; Caspase-3; Prognostic factors; Rituximab; Immunohistochemistry
AB Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients’ outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (RCHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients’ outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients’ outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP.
C1 [Mitrovic, Zdravko] University Hospital Center Zagreb, Division of Hematology and Department of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Ilic, Ivana] University Hospital Center Zagreb, Department of PathologyZagreb, Croatia.
[Aurer, Igor] University Hospital Center Zagreb, Division of Hematology and Department of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Kinda, Basic Sandra] University Hospital Center Zagreb, Division of Hematology and Department of MedicineZagreb, Croatia.
[Radman, Ivo] University Hospital Center Zagreb, Division of Hematology and Department of MedicineZagreb, Croatia.
[Dotlic, Snjezana] University Hospital Center Zagreb, Department of PathologyZagreb, Croatia.
[Ajdukovic, Radmila] University Hospital Dubrava, Department of Medicine, Av. Gojka Suska 6, 10 000 Zagreb, Croatia.
[Labar, Boris] University Hospital Center Zagreb, Division of Hematology and Department of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
RP Mitrovic, Z (reprint author), University Hospital Center Zagreb, Division of Hematology and Department of Medicine, 10 000 Zagreb, Croatia.
EM mitrovic@mef.hr
CR Feugier P, Van Hoof A, Sebban C et al, 2005, Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23:4117–4126
Pfreundschuh M, Trumper L, Osterborg A et al, 2006, CHOPlike chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B cell lymphoma: a randomized controlled trial by the MabThera International Trial, MInT, Group. Lancet Oncol 7:379–391
Cvetkovic RS, Perry CM, 2006, Rituximab—a review of its use in Non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 66:791–820
Guha M, Altieri DC, 2009, Survivin as a global target of intrinsic tumor suppression networks. Cell Cycle 8:2708–2710
Li F, Yang J, Ramnath N et al, 2005, Nuclear or cytoplasmic expression of survivin: what is the significance? Int J Cancer 114:509–512
Watanuki-Miyauchi R, Kojima Y, Tsurumi H et al, 2005, Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. Pathol Int 55:324–330
Karabatsou K, Pal P, Dodd S et al, 2006, Expression of survivin, platelet-derived growth factor A, PDGF-A, and PDGF receptor alpha in primary central nervous system lymphoma. J Neurooncol 79:171–179
Lin L, Min Z, Ping Z, 2007, Expression of PLK1 and survivin in diffuse large B-cell lymphoma. Leuk Lymphoma 48:2179–2183
Mainou-Fowler T, Overman LM, Dignum H et al, 2008, A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2. Int J Oncol 32:59–68
Adida C, Haioun C, Gaulard P et al, 2000, Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 96:1921–1925
Aktas S, Kargi A, Olgun N et al, 2009, Prognostic significance of cell proliferation and apoptosis-regulating proteins in Epstein-Barr Virus positive and negative pediatric non-Hodgkin’s lymphoma. Pathol Oncol Res 15:345–350
Paydas S, Seydaoglu G, Ergin M et al, 2009, Prognostic significance of angiogenic/lymphangiogenic, anti-apoptotic, inflammatory and viral factors in 88 cases with diffuse large B cell lymphoma and review of the literature. Leuk Res 33:1627–1635
Hans CP, Weisenburger DD, Greiner TC et al, 2005, Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol 18:1377–1384
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Donoghue S, Baden SH, Lauder I et al, 1999, Immunohistochemical localization of caspase-3 correlates with clinical outcome in B-cell diffuse large cell lymphoma. Cancer Res 59:5386–5391
ten Berge RL, Meijer CJ, Dukers DF et al, 2002, Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma. Blood 99:4540–4546
Muris JJ, Cillessen SA, Vos Wet al, 2005, Immunohistochemical profiling of caspase signalling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. Blood 105:2916–2923
Cheson BD, Horning SJ, Coiffier B et al, 1999, Report of an international workshop to standardize response criteria for non- Hodgkin’s lymphomas. NCI Sponsored International Working group. J Clin Oncol 17:1244–1253
The International Non-Hodgkin’s Lymphoma Prognostic Factors Project, 1993, A predictive model for aggressive non-hodgkin’s lymphoma. N Engl J Med 329:987–994
Mounier N, Briere J, Gisselbrecht C et al, 2003, Rituximab plus CHOP, R-CHOP, overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma, DLBCL). Blood 101:4279–4284
Ansell SM, Arendt BK, Grote DM et al, 2004, Inhibition of survivin expression suppresses the growth of aggressive non- Hodgkin’s lymphoma. Leukemia 18:616–623
Tolcher AW, Mita A, Lewis LD et al, 2008, Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin. J Clin Oncol 26:5198–5203
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 243
EP 247
DI 10.1007/s12253-010-9304-4
PG 5
ER
PT J
AU Gergely, L
Vancsa, A
Miltenyi, Zs
Simon, Zs
Barath, S
Illes,
AF Gergely, Lajos
Vancsa, Andrea
Miltenyi, Zsofia
Simon, Zsofia
Barath, Sandor
Illes, Arpad
TI Pretreatment T Lymphocyte Numbers Are Contributing to the Prognostic Significance of Absolute Lymphocyte Numbers in B-cell Non-Hodgkins Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NHL; Lymphocytes; T cells; Prognostic factors
ID NHL; Lymphocytes; T cells; Prognostic factors
AB Targeted immuno-chemotherapy resulted in greatly improved survival of B cell lymphoma patients. Several prognostic markers are investigated, amongst them the pretreatment absolute lymphocyte numbers. We investigated lymphocyte subpopulations and correlated this data with prognosis of patients. 88 patients (mean age: 56 years, 18–88, median follow up 32 months) with B cell lymphomas were investigated. There were 51 DLBCL, 16 Follicular NHL, 4 MALT, 7 Marginal Zone NHL, 10 Small lymphocytic cases were investigated. Our data showed that overall survival was statistically significant up to the 0.9 G/l absolute lymphocyte numbers as dividers between the subgroups. The CD19+ B cell numbers, or the CD56+/CD3- NK cell numbers did not represent any significant differences between subgroups. However CD3+, CD4+ and CD8+ T cells were differentiating statistically significant subgroups. Pretreatment CD3+ cell number less than 700/ul and CD8+ cell number less than 200/ul were corresponding with significantly inferior overall survival. These could be verified in the bad prognostic IPI group as well. Our data further support the importance of pretreatment lymphocyte numbers and highlight CD3+ and CD8+ lymphocytes to be the key factors in predicting outcome.
C1 [Gergely, Lajos] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz zs. Krt. 22, 4032 Debrecen, Hungary.
[Vancsa, Andrea] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz zs. Krt. 22, 4032 Debrecen, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz zs. Krt. 22, 4032 Debrecen, Hungary.
[Simon, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz zs. Krt. 22, 4032 Debrecen, Hungary.
[Barath, Sandor] University of Debrecen, Medical and Health Center, 3rd Department of MedicineDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz zs. Krt. 22, 4032 Debrecen, Hungary.
RP Gergely, L (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
EM lgergely@iiibel.dote.hu
CR Yamaguchi M, Nakamura N, Suzuki R, Kagami Y, Okamoto M, Ichinohasama R et al, 2008, De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients. Haematologica 93(8):1195–1202
Marini G, Ippoliti G, Ascari E, Casirola G, 1972, The absolute lymphocyte count in Hodgkin’s disease as an aid in survival prognosis. Haematologica 57(12):822–831
Decaudin D, Des Guetz G, Mathiot C, Dumont J, Hubert P, Vincent-Salomon A et al, 2003, Absolute lymphocyte count as a predictive factor for response to monoclonal anti-CD20 antibody therapy. Ann Oncol 14(1):171–172
Siddiqui M, Ristow K, Markovic SN, Witzig TE, Habermann TM, Colgan JP et al, 2006, Absolute lymphocyte count predicts overall survival in follicular lymphomas. Br J Haematol 134, 6):596–601
Czuczman MS, Grillo-Lopez AJ, Alkuzweny B, Weaver R, Larocca A, McLaughlin P, 2006, Prognostic factors for non-Hodgkin’s lymphoma patients treated with chemotherapy may not predict outcome in patients treated with rituximab. Leuk Lymphoma 47, 9):1830–1840
Wahlin BE, Sander B, Christensson B, Kimby E, 2007, CD8+ Tcell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma. Clin Cancer Res 13(2 Pt 1):388–397
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Talaulikar D, Choudhury A, Shadbolt B, Brown M, 2008, Lymphocytopenia as a prognostic marker for diffuse large B cell lymphomas. Leuk Lymphoma 49(5):959–964
Oki Y, Yamamoto K, Kato H, Kuwatsuka Y, Taji H, Kagami Yet al, 2008, Low absolute lymphocyte count is a poor prognostic marker in patients with diffuse large B-cell lymphoma and suggests patients’ survival benefit from rituximab. Eur J Haematol 81(6):448–453
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Kim DH, Baek JH, Chae YS, Kim YK, Kim HJ, Park YH et al, 2007, Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma. Leukemia 21(10):2227–2230
Seshadri T, Pintilie M, Keating A, Crump M, Kuruvilla J, 2008, The relationship between absolute lymphocyte count with PFS in patients with Hodgkin’s lymphoma undergoing autologous hematopoietic cell transplant. Bone Marrow Transplant 42(1):29–34
De Angulo G, Yuen C, Palla SL, Anderson PM, Zweidler-McKay PA, 2008, Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies. Cancer 112(2):407–415
Yano Y, Ueda Y, Itoh T, Fuji N, Okugawa K, Naito K et al, 2006, A new strategy using autologous dendritic cells and lymphokine-activated killer cells for cancer immunotherapy: efficient maturation of DCs by co-culture with LAK cells in vitro. Oncol Rep 16(1):147–152
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 249
EP 255
DI 10.1007/s12253-010-9306-2
PG 7
ER
PT J
AU Chen, X
Liao, J
Lu, Y
Duan, X
Sun, W
AF Chen, Xiong
Liao, Jie
Lu, YeBin
Duan, XiaoHui
Sun, Weijia
TI Activation of the PI3K/Akt Pathway Mediates Bone Morphogenetic Protein 2-Induced Invasion of Pancreatic Cancer Cells Panc-1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PI3K/Akt; Bone morphogenetic protein-2 (BMP-2); Invasion; Epithelial to mesenchymal transition (EMT)
ID PI3K/Akt; Bone morphogenetic protein-2 (BMP-2); Invasion; Epithelial to mesenchymal transition (EMT)
AB Bone morphogenetic proteins (BMPs) signaling has an emerging role in pancreatic cancer. However, because of the multiple effects of different BMPs, no final conclusions have been made as to the role of BMPs in pancreatic cancer. In our studies, we have focused on bone morphogenetic protein 2(BMP-2) because it induces an epithelial to mesenchymal transition (EMT) and accelerates invasion in the human pancreatic cancer cell line Panc-1. It has been reported that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates invasion of gastric and colon cancer cells, which is unrevealed in pancreatic cancer cells. The objective of our study was to investigate whether BMP-2 mediated invasion might pass through the PI3K/Akt pathway. Our results show that expression of phosphorylation of Akt was increased by treatment with BMP-2, but not Noggin, a BMP-2 antagonist. Then pretreatment of Panc-1 cells with LY294002, an inhibitor of the PI3K/AKT pathway, significantly inhibited BMP-2-induced EMT and invasiveness. The data suggest that BMP-2 accelerates invasion of panc-1 cells via the PI3K/AKT pathway in panc-1 cells, which gives clues to searching new therapy targets in advanced pancreatic cancer.
C1 [Chen, Xiong] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
[Liao, Jie] Central South University, XiangYa Hospital, Department of Endocrinology, 410008 Changsha, China.
[Lu, YeBin] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
[Duan, XiaoHui] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
[Sun, Weijia] Central South University, Institute of Pancreatic Diseases, 410008 Changsha, China.
RP Sun, W (reprint author), Central South University, Institute of Pancreatic Diseases, 410008 Changsha, China.
EM sunweijiays@hotmail.com
CR Gansler T, Brawley OW, 2010, Cancer statistics, 2010. CA Cancer J Clin 60(1):1
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ten Dijke P, Korchynskyi E, Valdimarsdottir G, Goumans MJ, 2003, Controlling cell fate by bone morphogenetic protein receptors. Mol Cell Endocrinol 211(1–2):105–113
Yamamoto Y, Oelgeschlager M, 2004, Regulation of bone morphogenetic proteins in early embryonic development. Naturwissenschaften 91(11):519–534
Mukhopadhyay A, McGuire T, Peng CY, Kessler JA, 2009, Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation. Development 136(15): 2633–2642
Mukhopadhyay P, Webb CL, Warner DR, Greene RM, Pisano MM, 2008, BMP signaling dynamics in embryonic orofacial tissue. J Cell Physiol 216(3):771–779
Shimizu T, Tanaka T, Iso T, Kawai-Kowase K, Kurabayashi M, 2009, Bone morphogenetic protein-2, BMP-2, and BMP-7 act as instructive factors to specify notch signaling controlling smooth muscle cell phenotype. Circulation 120(18):S1114
Gong SG, Guo C, 2003, Bmp4 gene is expressed at the putative site of fusion in the midfacial region. Differentiation 71(3):228– 236
Gordon KJ, Kirkbride KC, How T, Blobe GC, 2009, Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2. Carcinogenesis 30(2):238–248
Beck SE, Carethers JM, 2007, BMP suppresses PTEN expression via RAS/ERK signaling. Cancer Biol Ther 6(8):1313–1317
Ma J, Sawai H, Matsuo Y, Ochi N, Yasuda A, Takahashi H, Wakasugi T, Funahashi H, Sato M, Takeyama H, 2008, IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res
Stoll V, Calleja V, Vassaux G, Downward J, Lemoine NR, 2005, Dominant negative inhibitors of signalling through the phosphoinositol 3-kinase pathway for gene therapy of pancreatic cancer. Gut 54(1):109–116
Reichert M, Saur D, Hamacher R, Schmid RM, Schneider G, 2007, Phosphoinositide-3-kinase signaling controls S-phase kinase-associated protein 2 transcription via E2F1 in pancreatic ductal adenocarcinoma cells. Cancer Res 67(9):4149–4156
Chen PH, Yang CR, 2008, Decoy receptor 3 expression in AsPC-1 human pancreatic adenocarcinoma cells via the phosphatidylinositol 3-kinase-, Akt-, and NF-kappa B-dependent pathway. J Immunol 181(12):8441–8449
Liu DP, Zhang Y, Dang CX, Ma QY, Lee W, Chen W, 2007, siRNA directed against TrkA sensitizes human pancreatic cancer cells to apoptosis induced by gemcitabine through an inactivation of PI3K/Akt-dependent pathway. Oncol Rep 18(3):673–677
Yip-Schneider MT, Wiesenauer CA, Schmidt CM, 2003, Inhibition of the phosphatidylinositol 3′-kinase signaling pathway increases the responsiveness of pancreatic carcinoma cells to sulindac. J Gastrointest Surg 7(3):354–363
Kang MH, Kang HN, Kim JL, Kim JS, Oh SC, Yoo YA, 2009, Inhibition of PI3 kinase/Akt pathway is required for BMP2- induced EMT and invasion. Oncol Rep 22(3):525–534
Kang MH, Kim JS, Seo JE, Oh SC, Yoo YA, 2010, BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase, PI3K)/Akt pathway. Exp Cell Res 316(1):24–37
Hamada S, Satoh K, Hirota M, Kimura K, Kanno A, Masamune A, Shimosegawa T, 2007, Bone morphogenetic protein 4 induces epithelial-mesenchymal transition through MSX2 induction on pancreatic cancer cell line. J Cell Physiol 213(3):768–774
Amiri A, Noei F, Jeganathan S, Kulkarni G, Pinke DE, Lee JM, 2007, eEF1A2 activates Akt and stimulates Akt-dependent actin remodeling, invasion and migration. Oncogene 26(21):3027–3040
Liu H, Radisky DC, Nelson CM, Zhang H, Fata JE, Roth RA, Bissell MJ, 2006, Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2. Proc Natl Acad Sci USA 103(11):4134–4139
Meng Q, Xia C, Fang J, Rojanasakul Y, Jiang BH, 2006, Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Signal 18(12):2262–2271
Sugimori K, Matsui K, Motomura H, Tokoro T, Wang JY, Higa S, Kimura T, Kitajima I, 2005, BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/Akt-mediated NF-kappa B activation. J Bone Miner Metab 23(6):411–419
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Maddipatla S, Khoury T, Gibbs JF, Nasser E, Rutledge P, Iwata K, Black J, Javle M, 2007, Epithelial-mesenchymal transition, EMT, and role of p-Erk in surgically resected pancreatic cancer. Ann Surg Oncol 14(2):4
Roskelley CD, Somasiri AM, Tognon C, Sorensen P, Nielsen J, McNagny K, Huntsman D, Dedhar S, 2004, On the road to EMT: Genes and phenes that regulate tumor subtype-specific breast cancer progression. FASEB J 18(5):A761–A762
Spaderna S, Schmalhofer O, Hlubek F, Berx G, Eger A, Merkel S, Jung A, Kirchner T, Brabletz T, 2006, A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131(3):830–840
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 257
EP 261
DI 10.1007/s12253-010-9307-1
PG 5
ER
PT J
AU Khoor, A
Byrd-Gloster, LA
Nicosia, VS
AF Khoor, Andras
Byrd-Gloster, L Angela
Nicosia, V Santo
TI Expression of Thyroid Transcription Factor-1 in Malignant Pleural Effusions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TTF-1; Cytology; Pleural effusions; Lung; Adenocarcinoma; Malignant mesothelioma
ID TTF-1; Cytology; Pleural effusions; Lung; Adenocarcinoma; Malignant mesothelioma
AB Separating adenocarcinoma of the lung from nonpulmonary adenocarcinoma or malignant mesothelioma is difficult, especially in cytology specimens. Consequently, it is important to identify markers that may facilitate this distinction. Thyroid transcription factor-1 (TTF-1) is a homeodomain containing transcription factor expressed selectively in the thyroid, lung, and diencephalon. TTF-1 is also expressed in adenocarcinomas of the lung and is widely used as a pulmonary adenocarcinoma marker in surgical specimens. However, the utility of TTF-1 has rarely been investigated in cytology. In this study, we evaluated the expression of TTF-1 in malignant pleural effusions. The primary tumors included 26 pulmonary adenocarcinomas, 26 non-pulmonary adenocarcinomas (13 breast, 5 ovarian, 2 gastric, 2 prostatic, 1 esophageal, 1 colonic, 1 pancreatic and 1 renal) and 4 malignant mesotheliomas. Immunocytochemistry was performed on sections of cell blocks, using a mouse monoclonal TTF-1 antibody (clone 8G7G3/1) and a biotin-streptavidin detection system. Nuclear immunoreactivity for TTF-1 was detected in 19 pulmonary adenocarcinomas. All nonpulmonary adenocarcinomas and malignant mesotheliomas were negative. These data indicate that TTF-1 maintains its sensitivity (73%) and specificity (100%) in cell block preparations and is useful in separating adenocarcinoma of the lung from non-pulmonary adenocarcinoma and malignant mesothelioma in cytology specimens.
C1 [Khoor, Andras] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Road, 32224 Jacksonville, FL, USA.
[Byrd-Gloster, L Angela] Pathologists’ Laboratory, PCHermitage, TN, USA.
[Nicosia, V Santo] University of South Florida, College of Medicine, Department of Pathology and Cell BiologyTampa, FL, USA.
RP Khoor, A (reprint author), Mayo Clinic, Department of Laboratory Medicine and Pathology, 32224 Jacksonville, USA.
EM khoor.andras@mayo.edu
CR Johnston WW, 1985, The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 56:905–909
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Attanoos RL, Gibbs AR, 2003, ‘Pseudomesotheliomatous’ carcinomas of the pleura: a 10-year analysis of cases from the Environmental Lung Disease Research Group Cardiff. Histopathology 43:444–452
Lazzaro D, Price M, de Felice M, Di Lauro R, 1991, The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development 113:1093–1104
Stahlman MT, Gray ME, Whitsett JA, 1996, Expression of thyroid transcription factor-1(TTF-1, in fetal and neonatal human lung. J Histochem Cytochem 44:673–678
Whitsett JA, Glasser SW, 1998, Regulation of surfactant protein gene transcription. Biochim Biophys Acta 1408:303–311
Maeda Y, Dave V, Whitsett JA, 2007, Transcriptional control of lung morphogenesis. Physiol Rev 87:219–244
Katoh R, Kawaoi A, Miyagi E et al, 2000, Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization. Mod Pathol 13:570–576
Katoh R, Miyagi E, Nakamura N et al, 2000, Expression of thyroid transcription factor-1, TTF-1, in human C cells and medullary thyroid carcinomas. Hum Pathol 31:386–393
Burke LM, Rush WI, Khoor A et al, 1999, Alveolar adenoma: a histochemical, immunohistochemical, and ultrastructural analysis of 17 cases. Hum Pathol 30:158–167
Devouassoux-Shisheboran M, Hayashi T, Linnoila RI et al, 2000, A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies: TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium. Am J Surg Pathol 24:906–916
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Khoor A, Whitsett JA, Stahlman MT et al, 1999, Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. Hum Pathol 30:695–700
Folpe AL, Gown AM, Lamps LWet al, 1999, Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol 12:5–8
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 263
EP 267
DI 10.1007/s12253-010-9308-0
PG 5
ER
PT J
AU Ashtiani, OZ
Hasheminasab, SM
Ayati, M
Goulian, SB
Modarressi, HM
AF Ashtiani, Ousati Zahra
Hasheminasab, Sayed-Mohammad
Ayati, Mohsen
Goulian, Sabah Bareto
Modarressi, Hossein Mohammad
TI Are GSTM1, GSTT1 and CAG Repeat Length of Androgen Receptor Gene Polymorphisms Associated with Risk of Prostate Cancer in Iranian Patients?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; AR gene; CAG repeat; GSTM1; GSTT1
ID Prostate cancer; AR gene; CAG repeat; GSTM1; GSTT1
AB We conducted this study to investigate whether CAG repeat length in androgen receptor gene and GSTM1 and GSTT1 polymorphisms influence prostate cancer risk in Iranian newly diagnosed cancer patients compared to age-matched BPH group and healthy individuals. DNA from 110 pathologically-confirmed prostate cancer patients, 99 age-matched men with Benign Prostatic Hyperplasia (BPH) and 100 healthy individuals were extracted and amplified by polymerase chain reaction (PCR). PCR products were examined by electrophoresis and sequencing. The mean number of CAG repeat in prostate cancer patients was significantly smaller than normal (19.9 vs 22.8; p<0.0001) and BPH groups (19.9 vs 21.9; P<0.0001) The mean difference between normal individuals and BPH group was also significant (21.9 vs. 22.8; P=0.003). Presence of GSTM1 null genotype were significantly higher in cancer and BPH group vs. normal individuals (both P values< 0.0001). there was not seen association between GSTT1 null or positive genotype with cancer risk, but analysis of GSTM1 null and GSTT1 positive in combination was statistically associated with Prostate cancer risk (OR=8.4, 95% CI 1.53–46.73). Our results showed that CAG repeat polymorphism in AR gene may act as a risk modifier and GSTM1 null genotypes also may be contributed to prostate cancer susceptibility in Iranian patients.
C1 [Ashtiani, Ousati Zahra] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
[Hasheminasab, Sayed-Mohammad] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
[Ayati, Mohsen] Tehran University of Medical Sciences, Imam Khomeini General Hospital, Department of Urology TehranTehran, Iran.
[Goulian, Sabah Bareto] Biston Ultasound ClinicTehran, Iran.
[Modarressi, Hossein Mohammad] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
RP Modarressi, HM (reprint author), Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical Genetics, Tehran, Iran.
EM modaresi@sina.tums.ac.ir
CR Foley R, Hollywood D, Lawler M, 2004, Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease. Endocr Relat Cancer 11(15369449):477–488
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 269
EP 275
DI 10.1007/s12253-010-9309-z
PG 7
ER
PT J
AU Chatzizacharias, AN
Giaginis, C
Gatzidou, E
Tsourouflis, G
Sfiniadakis, I
Alexandrou, P
Theocharis, ES
AF Chatzizacharias, A Nikolaos
Giaginis, Constantinos
Gatzidou, Elisavet
Tsourouflis, Gerasimos
Sfiniadakis, Ioannis
Alexandrou, Paraskevi
Theocharis, E Stamatios
TI Expression and Clinical Significance of FAK and Src Proteins in Human Endometrial Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FAK; Src; Clinical significance; Immunohistochemistry; Endometrial adenocarcinoma
ID FAK; Src; Clinical significance; Immunohistochemistry; Endometrial adenocarcinoma
AB Focal Adhesion Kinase (FAK) is a protein tyrosine kinase, localised in the focal adhesions, which, upon activation interacts with Src, another tyrosine kinase, regulating several cellular signalling pathways. Both enzymes have been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK and Src expression in cases of endometrial adenocarcinoma. The total (t) and the activated, phosphorylated (p) forms of FAK and Src proteins were assessed immunohistochemically in tumour specimens obtained from 43 endometrial adenocarcinoma patients and were statistically analyzed in relation to various clinicopathological parameters and tumour proliferative capacity, reflected by Ki-67 labelling index. t-FAK positivity was significantly correlated with FIGO disease stage (p=0.031), and t-FAK overexpression with patients’ age (p=0.015). No statistically significant correlation was identified between t-FAK staining intensity, t-Src positivity, overexpression or staining intensity and any of the clinicopathological parameters tested. No significant correlation was found between neither the positivity nor the intensity of staining of either p-FAk or p-Src with any of the parameters under study. Nonetheless, important, but non-significant, trends were identified between t-FAK staining intensity, t-Src positivity and overexpression and patients’ survival (log rank, p=0.122, p=0.090 and p=0.057 respectively). Similarly, p-FAK and p-Src staining characteristics seemed to correlate, even though nonsignificantly, with patients’ survival (log rank, p=0.051 and p=0.070 for p-FAK and p-Src expression, respectively; log rank, p=0.134 and p=0.110 for p-FAK and p-Src staining intensity, respectively). These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress and render further research in this field a necessity.
C1 [Chatzizacharias, A Nikolaos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
[Giaginis, Constantinos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
[Gatzidou, Elisavet] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
[Tsourouflis, Gerasimos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
[Sfiniadakis, Ioannis] Naval Hospital Athens, Department of PathologyAthens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
[Theocharis, E Stamatios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75, Mikras Asias streetm, Goudi, GR11527 Athens, Greece.
RP Theocharis, ES (reprint author), University of Athens, Medical School, Department of Forensic Medicine and Toxicology, GR11527 Athens, Greece.
EM theocharis@ath.forthnet.gr
CR Guan JL, Shalloway D, 1992, Regulation of focal adhesionassociated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 358:690–692
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Xing Z, Chen HC, Nowlen JK, Taylor SJ, Shalloway D, Guan JL, 1994, Direct interaction of v-Src with the focal adhesion kinase mediated by the Src SH2 domain. Mol Biol Cell 5:413–421
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Chatzizacharias NA, Kouraklis GP, Theocharis SE, 2007, Focal adhesion kinase: a promising target for anticancer therapy. Expert Opin Ther Targets 11:1315–1328
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Giaginis CT, Vgenopoulou S, Tsourouflis GS, Politi EN, Kouraklis GP, Theocharis SE, 2009, Expression and clinical significance of focal adhesion kinase in the two distinct histological types, intestinal and diffuse, of human gastric adenocarcinoma. Pathol Oncol Res 15:173–181
Chatzizacharias NA, Giaginis C, Diamanto Zizi-Serbetzoglou D et al, 2010, Evaluation of the clinical significance of Focal Adhesion Kinase and Src expression in human pancreatic ductal adenocarcinoma. Pancreas 39:930–936
Macwhinnie N, Monaghan H, 2004, The use of P53, PTEN, and C-erbB-2 to differentiate uterine serous papillary carcinoma from endometrioid endometrial carcinoma. Int J Gynecol Cancer 14:938–946
Sobel G, Nemeth J, Kiss A, Lotz G, Szabo I, Udvarhelyi N, Schaff Z, Paska C, 2006, Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma. Gynec Oncol 103:591–598
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 277
EP 285
DI 10.1007/s12253-010-9310-6
PG 9
ER
PT J
AU Ieni, A
Barresi, V
Grosso, M
Speciale, G
Rosa, AM
Tuccari, G
AF Ieni, Antonio
Barresi, Valeria
Grosso, Maddalena
Speciale, Giuseppe
Rosa, A Michele
Tuccari, Giovanni
TI Does Lactoferrin Behave as an Immunohistochemical Oncofetal Marker in Bone and Cartilage Human Neoplasms?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone tumours; Fetal tissue; Immunohistochemistry; Lactoferrin; Oncofetal antigens
ID Bone tumours; Fetal tissue; Immunohistochemistry; Lactoferrin; Oncofetal antigens
AB By immunohistochemistry, lactoferrin (LF) has been extensively investigated in human neoplastic tissues; moreover, LF is able to promote bone growth in a murine model. Until now, no systematic studies on human osteocartilagineous fetal samples have been performed in comparison to corresponding neoplastic specimens to verify if LF may represent an oncofetal marker in this field of pathology. By a monoclonal antibody (clone 1A1; Biodesign International; w.d. 1:75) the distribution pattern of LF in bones of 25 human fetal tissues (8–34 gestation weeks), 10 adults (47–82 years) and 30 cartilage as well as 27 bone tumours (9–76 years) was analyzed. LF was encountered in 23/57 cases of osteocartilagineous tumors and namely in 10/10 giant cell tumours, 5/7 osteoid osteomas, 3/3 chondroblastomas, 3/3 chondromyxoid fibromas, 1/1 myeloma, 1/1 adamantinoma. No LF immunoexpression was detected in osteosarcomas, chondrosarcomas, ossifying fibromas, osteochondroma and enchondromas. In embryo-fetal tissues, LF immunoreactivity was localized in mesenchymal cells as well as in chondroblasts at the 8th gestational week and in immature osteocytes and osteoblasts up to the 18th gestation week, with a considerable decrease by the 24th week. No LF expression was found in any bone district since the 30th and up to the 34th week of gestation as well as in corresponding adult samples. Our findings indicate a role for LF as a bone growth regulator in the early phases of the human endochondral ossification, although the hypothesis of LF as oncofetal marker appears questionable in bone tumours.
C1 [Ieni, Antonio] Azienda Ospedaliera Universitaria, Department of Human Pathology, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
[Barresi, Valeria] Azienda Ospedaliera Universitaria, Department of Human Pathology, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
[Grosso, Maddalena] Azienda Ospedaliera Universitaria, Department of Human Pathology, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
[Speciale, Giuseppe] Azienda Ospedaliera Universitaria, Department of Human Pathology, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
[Rosa, A Michele] Azienda Ospedaliera Universitaria, Orthopaedics Clinic, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
[Tuccari, Giovanni] Azienda Ospedaliera Universitaria, Department of Human Pathology, Pad. D, Via Consolare Valeria, 98125 Messina, Italy.
RP Ieni, A (reprint author), Azienda Ospedaliera Universitaria, Department of Human Pathology, 98125 Messina, Italy.
EM calaienco@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 287
EP 293
DI 10.1007/s12253-010-9311-5
PG 7
ER
PT J
AU Bouanene, H
Hadj Kacem, H
Ben Fatma, L
Ben Limem, H
Ben Ahmed, S
Yakoub, S
Miled, A
AF Bouanene, Houda
Hadj Kacem, Hassen
Ben Fatma, Leila
Ben Limem, Halima
Ben Ahmed, Slim
Yakoub, Salwa
Miled, Abdelhedi
TI Polymorphisms in the MUC16 Gene: Potential Implication in Epithelial Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MUC16; Polymorphism; CA125; Epithelial ovarian cancer
ID MUC16; Polymorphism; CA125; Epithelial ovarian cancer
AB MUC16 plays an important role in epithelial ovarian cancer. In this paper, we studied the association between two tags SNPs of MUC16 and the risk of epithelial ovarian cancer. We aimed also to test the association between these tags SNPs and elevated level of the protein CA125. We analyzed a collection of 117 cases. Forty-one samples of patients with epithelial ovarian cancer and 76 samples from Tunisian volunteers were genotyped for two synonymous coding tags SNPs of the MUC16 gene (rs1596797, A/C and rs2547065, C/G) using polymerase chain reaction and sequencing. For the rs1596797 SNP, there was no significant difference in genotype distribution, a rare variation observed in only one patient. For the polymorphism rs2547065, mean CA125 levels were 24 and 78 UI/ml in patients with GG and GC genotypes versus 230 UI/ml in patients with CC genotype (P=0.36). Compared to the C/C genotype, the ‘G’ allele (C/G+G/G genotypes) did not significantly modified the risk of developping epithelial ovarian cancer (OR=0.43; 95% CI). As for the polymorphism rs1596797, compared to the C/C genotype, the ‘A’ allele (C/A+A/A genotypes) did not significantly modified the risk of developping epithelial ovarian cancer (OR=881.7; 95% CI). MUC16 gene polymorphisms selected in this study are neither involved in genetic predisposition to epithelial ovarian cancer nor associated with CA125 level.
C1 [Bouanene, Houda] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
[Hadj Kacem, Hassen] University of Sfax, Centre de Biotechnologie de SfaxSfax, Tunisia.
[Ben Fatma, Leila] CHU Farhat Hached, Service of OncologySousse, Tunisia.
[Ben Limem, Halima] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
[Ben Ahmed, Slim] CHU Farhat Hached, Service of OncologySousse, Tunisia.
[Yakoub, Salwa] Center of Blood TransfusionSousse, Tunisia.
[Miled, Abdelhedi] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
RP Bouanene, H (reprint author), CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
EM bouanenehouda2@yahoo.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 295
EP 299
DI 10.1007/s12253-010-9314-2
PG 5
ER
PT J
AU Biro, A
Fodor, Z
Major, J
Tompa, A
AF Biro, Anna
Fodor, Zoltan
Major, Jeno
Tompa, Anna
TI Immunotoxicity Monitoring of Hospital Staff Occupationally Exposed to Cytostatic Drugs
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD antigens; Cytostatic drug; Immunotoxicity; Lymphocyte phenotype; Occupational exposure; Oxidative burst
ID CD antigens; Cytostatic drug; Immunotoxicity; Lymphocyte phenotype; Occupational exposure; Oxidative burst
AB The aim of our study was to investigate the immunotoxicity of occupational cytostatic drug exposure, and to assess the possible effect of confounding factors, such as age and smoking. In this human study, the immunotoxic effect of antineoplastic drugs was investigated among 306 nurses working in oncology chemotherapy units. Results were compared to 98 non-exposed women. The immune status of the subjects was characterized by immune phenotyping of peripheral blood lymphocytes by flow cytometry, using monoclonal antibodies against surface antigens (CD3, CD4, CD8, CD19, CD25, CD45, CD56 and CD71). The killing ability of neutrophil leukocytes was assessed by the measurement of reactive oxygen intermediate production. Occupational exposure to antineoplastic drugs caused shifts in the major lymphocyte subpopulations, resulting in a statistically significant increase in the ratio of B cells. Cytostatic drug exposure also manifested itself in a decreased frequency of CD25 positive, activated T lymphocytes, and increased oxidative burst of neutrophil granulocytes, both of which may have a functional impact on the immune system of exposed subjects. In the younger subjects exposure also caused a shift in T cell subpopulations: a reduction in the cytotoxic T cell population lead to an elevated Th/Tc ratio. In the exposed group, smoking increased activation of T lymphocyte subpopulations. In conclusion, we have demonstrated that low dose occupational cytostatic drug exposure is immunotoxic, and age and smoking modify the effect of exposure.
C1 [Biro, Anna] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, Nagyvarad ter 2, H-1096 Budapest, Hungary.
[Fodor, Zoltan] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, Nagyvarad ter 2, H-1096 Budapest, Hungary.
[Major, Jeno] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, Nagyvarad ter 2, H-1096 Budapest, Hungary.
[Tompa, Anna] Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, Nagyvarad ter 2, H-1096 Budapest, Hungary.
RP Biro, A (reprint author), Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont, Orszagos Kemiai Biztonsagi Intezet, Citogenetikai es Molekularis Toxikologiai Osztaly, H-1096 Budapest, Hungary.
EM biro.anna@okbi.antsz.hu
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Jakab MG, Major J, Tompa A, 2001, Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health 62:307–318
Connor TH, McDiarmid MA, 2006, Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin 56:354–365
Sorsa M, Anderson D, 1996, Monitoring of occupational exposure to cytostatic anticancer agents. Mutat Res 355:253–261
Sabbioni ME, Castiglione M, Hurny C, Siegrist HP, Bacchi M, Bernhard J et al, 1999, Interaction of tamoxifen with concurrent cytotoxic adjuvant treatment affects lymphocytes and lymphocyte subsets counts in breast cancer patients. Support Care Cancer 7:149–153
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Zielinski CC, Muller C, Kubista E, Staffen A, Eibl MM, 1990, Effects of adjuvant chemotherapy on specific and non-specific immune mechanisms. Acta Med Austriaca 17:11–14
Spatari G, Fenga C, Minciullo PL, Di Pasquale G, Cacciola A, Ventura-Spagnolo E et al, 2005, Modification of interleukin-15 serum levels in workers exposed to chemotherapeutic agents. Mediators Inflamm 1:60–62
Biro A, Pallinger E, Major J, Jakab MG, Klupp T, Falus A, Tompa A, 2002, Lymphocyte phenotype analysis and chromosome aberration frequency of workers occupationally exposed to styrene, benzene, polycyclic aromatic carbohydrates or mixed solvents. Immunol Lett 81:133–140
Biro A, Pallinger E, Falus A, Tompa A, 2004, Characterization of chemically exposed groups by immunotoxicological methods. Hungarian Oncology 48:137–139
Tompa A, Jakab M, Biro A, Magyar B, Fodor Z, Klupp T, Major J, 2006, Chemical safety and health conditions among Hungarian hospital nurses. Ann N Y Acad Sci 1076:635–648
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Environmental Health Criteria 180: Principles and methods for assessing direct immunotoxicity associated with exposure to chemicals. World Health Organization, Geneva, 1992
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 301
EP 308
DI 10.1007/s12253-010-9317-z
PG 8
ER
PT J
AU Demir, R
Peros, G
Hohenberger, W
AF Demir, Resit
Peros, Georgios
Hohenberger, Werner
TI Definition of the “Drug-Angiogenic-Activity-Index” that Allows the Quantification of the Positive and Negative Angiogenic Active Drugs: A Study Based on the Chorioallantoic Membrane Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiogenesis; Chorioallantoic membrane; Drug angiogenic index; Antiangiogenic therapy
ID Angiogenesis; Chorioallantoic membrane; Drug angiogenic index; Antiangiogenic therapy
AB Since the introduction of the angiogenic therapy by Folkman et al. in the 1970’ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the "Drug-Angiogenic-Activity-Index" of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the "Drug Angiogenic Activity Index" by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {ΔVIS[Drug]−ΔVIS[Control]} / Δ VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a −1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the "Drug-Angiogenic-Activity-Index" in the preclinical phase will give us an impact of effectivness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family.
C1 [Demir, Resit] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, 91054 Erlangen, Germany.
[Peros, Georgios] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, 91054 Erlangen, Germany.
[Hohenberger, Werner] University of Erlangen, Department of Surgery, Krankenhausstrasse 12, 91054 Erlangen, Germany.
RP Demir, R (reprint author), University of Erlangen, Department of Surgery, 91054 Erlangen, Germany.
EM r.demir@gmx.net
CR Folkman J, 1971, Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
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Saltz LB, Lenz HJ, Kindler HL, Hochster HS, Wadler S, Hoff PM, Kemeny NE, Hollywood EM, Gonen M, Quinones M, Morse M, Chen HX, 2007, Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 25:4557–4561
Ribatti D, Vacca A, Roncali L, Dammacco F, 1996, The chick embryo chorioallantoic membrane as a model for in vivo research on angiogenesis. Int J Dev Biol 40:1189–1197
Wilting J, Christ B, Bokeloh M, 1991, A modified chorioallantoic membrane, CAM, assay for qualitative and quantitative study of growth factors. Studies on the effects of carriers, PBS, angiogenin, and bFGF. Anat Embryol, Berl, 183:259–271
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Ribatti D, Gualandris A, Bastaki M, Vacca A, Iurlaro M, Roncali L, Presta M, 1997, New model for the study of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane: the gelatin sponge/chorioallantoic membrane assay. J Vasc Res 34:455–463
Kunzi-Rapp K, Genze F, Kufer R, Reich E, Hautmann RE, Gschwend JE, 2001, Chorioallantoic membrane assay: vascularized 3-dimensional cell culture system for human prostate cancer cells as an animal substitute model. J Urol 166:1502–1507
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 309
EP 313
DI 10.1007/s12253-010-9318-y
PG 5
ER
PT J
AU Lakosi, F
Antal, G
Vandulek, Cs
Kovacs,
Toller, LG
Rakasz, I
Bajzik, G
Hadjiev, J
Bogner, P
Repa, I
AF Lakosi, Ferenc
Antal, Gergely
Vandulek, Csaba
Kovacs, Arpad
Toller, L Gabor
Rakasz, Istvan
Bajzik, Gabor
Hadjiev, Janaki
Bogner, Peter
Repa, Imre
TI Open MR-Guided High-Dose-Rate (HDR) Prostate Brachytherapy: Feasibility and Initial Experiences Open MR-Guided High-Dose-Rate (HDR) Prostate Brachytherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HDR; Brachytherapy; Image guidance; Open MRI; Prostate cancer
ID HDR; Brachytherapy; Image guidance; Open MRI; Prostate cancer
AB The aim of our pilot study was to demonstrate the feasibility and dosimetric quality of MR-guided HDR prostate brachytherapy in a low-field 0.35T open MRI scanner and to present our initial clinical experiences. 16 patiets with intermediate- to high-risk localized prostate cancer were treated with 46–60 Gy of external beam radiotherapy preceded and/or followed by an 8 Gy MR-guided HDR boost. For interventions an MR compatible custom-made system, coaxial needles and plastic catheters were used. Template reconstruction, trajectory planning, image guidance, contouring and treatment planning were exclusively based on MR images. For treatment planning, dose-point- and anatomy-based inverse planning optimization was used. Image quality was found to be good to excellent in almost all cases. The mean catheter placement accuracy modeled by Rayleigh distribution was 2.9 mm with a sigma value of 2.3 mm. The mean and standard deviation (SD) of the dosimetric results for the target volume were the following: V100: 94.2±4.3%, V150: 43.9±6.8%, V200: 18.5±5.9%. The mean D0.1, D1 and D1 values for the intraprostatic urethra were 117.6±12.5%, 98.5±19.9% and 122.3±16.4%, respectively. Regarding the rectal wall the mean D0.1, D1 and D2 values were 77.3±7.2%, 64.8±7.5%, and 53.2±9.1%, respectively. The mean maximum dose for the inner rectal surface was 53.5±9.2%. No RTOG Grade 3 or worse acute toxicities were observed. Our method seems to be a promising approach for performing feasible, accurate and high-quality MR-guided HDR prostate brachytherapy. To determine the long term side effects and outcome higher number of patients, additional follow-up is needed.
C1 [Lakosi, Ferenc] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Antal, Gergely] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Vandulek, Csaba] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Kovacs, Arpad] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Toller, L Gabor] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Rakasz, Istvan] Kaposi Mor Teaching Hospital, Department of Urology, Tallian Gyula Street 20-32, 7400 Kaposvar, Hungary.
[Bajzik, Gabor] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Hadjiev, Janaki] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Bogner, Peter] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
[Repa, Imre] Kaposi Mor Teaching Hospital, Guba Sandor Street 40, 7400 Kaposvar, Hungary.
RP Kovacs, (reprint author), Kaposi Mor Teaching Hospital, 7400 Kaposvar, Hungary.
EM kovacs.arpad@sic.hu
CR Kasler M, Sz O, 2008, European and Hungarian national tasks in oncology. Magy Onkol 52:21–33
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Presti JC Jr, 2000, Prostate cancer: assessment of risk using digital rectal examination, tumor grade, prostate-specific antigen, and systematic biopsy. Radiol Clin North Am 38:49–58
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Van Lin EN, Futterer JJ, Heymink SW et al, 2006, IMRT boost dose planning on dominant intraprostatic lesions: gold markerbased three-dimensional fusion of CT with dynamic contrastenhanced and 1H-spectroscopic MRI. Int J Radiat Oncol Biol Phys 65:291–303
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Menard C, Susil RC, Choyke P et al, 2004, MRI-guided HDR prostate brachytherapy in standard 1.5T scanner. Int J Radiat Oncol Biol Phys 59:1414–1423
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 315
EP 324
DI 10.1007/s12253-010-9319-x
PG 10
ER
PT J
AU Szarvas, T
Jager, T
Becker, M
Tschirdewahn, S
Niedworok, Ch
Kovalszky, I
Rubben, H
Ergun, S
vom Dorp, F
AF Szarvas, Tibor
Jager, Tobias
Becker, Markus
Tschirdewahn, Stephan
Niedworok, Christian
Kovalszky, Ilona
Rubben, Herbert
Ergun, Suleyman
vom Dorp, Frank
TI Validation of Circulating MMP-7 Level as an Independent Prognostic Marker of Poor Survival in Urinary Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; MMP-7; Matrilysin; Metastasis; Plasma; Prognosis; Serum
ID Bladder cancer; MMP-7; Matrilysin; Metastasis; Plasma; Prognosis; Serum
AB Molecular marker analyses aiming a more accurate disease characterization and risk stratification of cancer patients provided several promising marker candidates in the last few years. However, recent reviews underlined the paramount importance of validation, since many of the initially promising results could not be confirmed in independent patient cohorts. If serum or plasma is a more appropriate sample to test for prognostic markers is a matter of debate. We recently found serum MMP-7 levels to correlate with poor patients’ prognosis in urinary bladder cancer. In this study, we examined associations of the MMP-7 plasma levels with clinical follow-up data in an independent cohort of bladder cancer patients to validate our former results and to assess if plasma is also suitable for MMP-7 analysis. Plasma levels of 97 patients and 22 controls were analyzed, using enzyme-linked immunosorbent assay. Associations between MMP-7 plasma concentrations and clinical data were assessed applying both univariate and multivariate analysis. Plasma MMP-7 levels were significantly higher in patients than in controls. Similarly to our former findings in sera, high MMP-7 plasma levels proved to be significant and independent predictors of both overall and disease-specific survival. In addition, we observed a metastasis-specific difference in MMP-7 levels between serum and plasma. In summary, we confirmed the prognostic relevance of circulating MMP-7 levels in an independent cohort of patients and concluded that circulating MMP-7 levels may help to identify bladder cancer patients at high-risk of disease progression who could benefit from an adjuvant chemotherapy or from an extended lymph node dissection.
C1 [Szarvas, Tibor] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Jager, Tobias] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Becker, Markus] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Tschirdewahn, Stephan] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Niedworok, Christian] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Rubben, Herbert] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Ergun, Suleyman] University Hospital of Essen, Institute of AnatomyEssen, Germany.
[vom Dorp, Frank] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
RP vom Dorp, F (reprint author), University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
EM frankvomdorp@web.de
CR Madersbacher S, Hochreiter W, Burkhard F, Thalmann GN, Danuser H, Markwalder R, Studer UE, 2003, Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol 21:690–696
Hautmann RE, Gschwend JE, de Petriconi RC, Kron M, Volkmer BG, 2006, Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 176:486–492
vom Dorp F, Borgermann C, Schenck M, Becker M, Rose A, Szarvas T, Rubben H, 2009, Role of lymphadenectomy in patients with invasive urothelial carcinoma of the bladder. Urologe 48:51– 53
Dyrskjot L, Zieger K, Real FX, Malats N, Carrato A, Hurst C, Kotwal S, Knowles M, Malmstrom PU, de la Torre M, Wester K, Allory Y, Vordos D, CaillaultA RF, Hein AM, Jensen JL, Jensen KM, Marcussen N, Orntoft TF, 2007, Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 13:3545–3551
Szarvas T, Becker M, vom Dorp F, Gethmann C, Totsch M, Bankfalvi A, Schmid KW, Romics I, Rubben H, Ergun S, 2010, Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci 101:1300–1308
Riley RD, Sauerbrei W, Altman DG, 2009, Prognostic markers in cancer: the evolution of evidence from single studies to metaanalysis, and beyond. Br J Cancer 100:1219–1229
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Bleeker SE, Moll HA, Steyerberg EW, Donders AR, Derksen- Lubsen G, Grobbee DE, Moons KG, 2003, External validation is necessary in prediction research: a clinical example. J Clin Epidemiol 56:826–832
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Ito TK, Ishii G, Saito S, Yano K, Hoshino A, Suzuki T, Ochiai A, 2009, Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. Blood 113:2363–2369
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Koskensalo S, Mrena J, Wiksten JP, Nordling S, Kokkola A, Hagstrom J, Haglund C, 2010, MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol 31:149–155
Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, Mukaiya M, Hirata K, Imai K, 2001, Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 19:1118–1127
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Maurel J, Nadal C, Garcia-Albeniz X, Gallego R, Carcereny E, Almendro V, Marmol M, Gallardo E, Auge JM, Longaron R, Martinez-Fernandez A, Molina R, Castells A, Gascon P, 2007,, 2007, Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 121:1066–1071
Martinez-Fernandez A, Garcia-Albeniz X, Pineda E, Visa L, Gallego R, Codony-Servat J, Auge JM, Longaron R, Gascon P, Lacy A, Castells A, Maurel J, 2009, Serum matrilysin levels predict outcome in curatively resected colorectal cancer patients. Ann Surg Oncol 16:1412–1420
Ramankulov A, Lein M, Johannsen M, Schrader M, Miller K, Jung K, 2008, Plasma matrix metalloproteinase-7 as a metastatic marker and survival predictor in patients with renal cell carcinomas. Cancer Sci 99:1188–1194
Szarvas T, Becker M, vom Dorp F, Meschede J, Scherag A, Bankfalvi A, Henning R, Schmid KW, Romics I, Rubben H, Ergun S, 2010, Elevated serum matrix metalloproteinase 7 levels predict poor prognosis after radical prostatectomy Int J Cancer, In press)
Szarvas T, Singer BB, Becker M, vom Dorp F, Jager T, Szendroi A, Riesz P, Romics I, Rubben H, Ergun S, 2010, Urinary MMP-7 level is associated with the presence of metastasis in bladder cancer. BJU Int, In press)
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 325
EP 332
DI 10.1007/s12253-010-9320-4
PG 8
ER
PT J
AU Mao, YL
Li, ZW
Lou, ChJ
Pang, D
Zhang, YQ
AF Mao, Yin-Ling
Li, Zhi-Wei
Lou, Chang-Jie
Pang, Da
Zhang, Yan-Qiao
TI PHOSPHO-STAT5 Expression is Associated with Poor Prognosis of Human Colonic Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon carcinoma; Immunohistochemistry; Prognosis; Signal transducer and activator of transcription- 5 (STAT5)
ID Colon carcinoma; Immunohistochemistry; Prognosis; Signal transducer and activator of transcription- 5 (STAT5)
AB The signal transducer and activator of transcription-5 (STAT5) protein has been shown to play an important role in tumor progression through stimulating cell proliferation and preventing apoptosis. STAT5 activation has been observed in a variety of human tumors and cancer cell lines. However, it is not clear how activated STAT5 is expressed in colon cancer. In this study, we aimed to investigate phospho-STAT5 (activated form of STAT5) expression and its relationship with the clinicopathological factors and overall survival of patients with colonic adenocarcinoma. A total of 121 histological samples were selected for this study. Immunohistochemistry was used to detect the expression of phospho-STAT5. Analysis of the immunohistochemical staining was based on the proportion of stained cells in the field: positive, >15% stained cells, and negative, <15% stained cells. Survival times were analyzed using the Kaplan-Meier method, and the differences between groups were assessed with the log-rank test. A multivariate Cox regression model was used for prognostic power analysis. Expression of phospho-STAT5 was observed in the cytoplasms of colonic adenocarcinoma cells. Univariate analysis showed that phospho-STAT5 immunoreactivity was correlated with the depth of tumor invasion (P-value=0.009), tumornode-metastasis (TNM) stage (P-value=0.048) and shorter overall survival times (P-value=0.026). Lymph node metastasis, distant metastasis and TNM stage were associated with shorter overall survival times (P-value range from 0.003-<0.001). Multivariate analysis showed that only distant metastasis was an independent predictor of overall survival time (P-value=0.016). Our findings first demonstrate that phospho-STAT5 is frequently present and active in colonic adenocarcinoma and related to poor prognosis.
C1 [Mao, Yin-Ling] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, No. 150, Haping Road, 150040 Harbin, Heilongjiang Province, China.
[Li, Zhi-Wei] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, No. 150, Haping Road, 150040 Harbin, Heilongjiang Province, China.
[Lou, Chang-Jie] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, No. 150, Haping Road, 150040 Harbin, Heilongjiang Province, China.
[Pang, Da] The Affiliated Tumor Hospital of Harbin Medical University, Department of Surgery, 150040 Harbin, Heilongjiang Province, China.
[Zhang, Yan-Qiao] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, No. 150, Haping Road, 150040 Harbin, Heilongjiang Province, China.
RP Zhang, YQ (reprint author), Harbin Medical University, Cancer Hospital, Department of Medical Oncology, 150040 Harbin, China.
EM yanqiaozhang@126.com
CR Lievre A, Bachet JB, Le Corre D et al, 2006, KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995
Galizia G, Lieto E, Ferraraccio F et al, 2004, Determination of molecular marker expression can predict clinical outcome in colon carcinomas. Clin Cancer Res 10:3490–3499
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Cotarla I, Ren S, Zhang Y et al, 2004, Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers. Int J Cancer 108:665–671
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Klampfer L, 2008, The role of signal transducers and activators of transcription in colon cancer. Front Biosci 13:2888–2899
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 333
EP 339
DI 10.1007/s12253-010-9321-3
PG 7
ER
PT J
AU Ru, GQ
Wang, HJ
Xu, WJ
Zhao, ZSh
AF Ru, Guo-Qing
Wang, Hui-Ju
Xu, Wen-Jun
Zhao, Zhong-Sheng
TI Upregulation of Twist in Gastric Carcinoma Associated with Tumor Invasion and Poor Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric carcinoma; Metastasis; RT-PCR; Twist expression
ID Gastric carcinoma; Metastasis; RT-PCR; Twist expression
AB Tumor invasion and metastasis are the most common causes of death in gastric carcinoma. Twist, a transcription factor of the basic helix-loop-helix class, reportedly regulates cancer metastasis and induces epithelial-mesenchymal transition (EMT). We evaluated the expression of Twist and its effect on cell migration in gastric carcinoma (GC). Twist expression was detected by real-time quantitative RT-PCR in gastric tumor tissue, metastatic lymph nodes and normal gastric tissue from 47 gastric carcinoma patients who had undergone gastrectomies with radical lymph node dissections without preoperative treatment. Twist expression was also analyzed immunohistochemically in 436 gastric cancer cases. GC tumor tissue and metastatic lymph nodes was upregulated compared with normal gastric mucosa (P<0.05). Twist protein expression differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph nodes (P<0.05) In stages I, II, and III, 5-year survival rates of patients with high Twist expression were significantly lower than in patients with low expression (P<0.05). In stage IV, Twist expression did not correlate with 5-year survival rates (P=0.07). Further multivariate analysis suggested that depth of invasion, lymph-node and distant metastases, TNM stage, and upregulation of TWIST were independent prognostic indicators for GC. Twist expression in gastric cancer is associated significantly with lymph-node and distant metastases, and poor prognosis. Twist may be a useful marker for the development, progression and metastasis of GC.
C1 [Ru, Guo-Qing] Wenzhou Medical University, 325035 Wenzhou, Zhejiang, China.
[Wang, Hui-Ju] Key Laboratory of Gastroenterology of Zhejiang Province, 310014 Hangzhou, China.
[Xu, Wen-Jun] Zhejiang Provincial People’s Hospital, Department of Pathology, 158 Shangtang Road, 310014 Hangzhou, Zhejiang, China.
[Zhao, Zhong-Sheng] Zhejiang Provincial People’s Hospital, Department of Pathology, 158 Shangtang Road, 310014 Hangzhou, Zhejiang, China.
RP Zhao, ZSh (reprint author), Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
EM zhaozhongsheng50@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 341
EP 347
DI 10.1007/s12253-010-9332-0
PG 7
ER
PT J
AU Goncalves, RA
Carneiro, JVA
Martins, I
de Faria, ASP
Ferreira, AM
de Mello, LRE
Fogaca, SH
Elia, CSC
de Souza, SPH
AF Goncalves, Rodrigues Andrea
Carneiro, Jose Vasconcellos Antonio
Martins, Ivanir
de Faria, Antonio Silvestre Paulo
Ferreira, Aparecida Maria
de Mello, Linhares Riello Eduardo
Fogaca, Soares Homero
Elia, Carvalho Siqueira Celeste
de Souza, Siffert Pereira Heitor
TI Prognostic Significance of p53 Protein Expression in Early Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Early gastric cancer; p53; Prognosis
ID Early gastric cancer; p53; Prognosis
AB Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren’s histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.
C1 [Goncalves, Rodrigues Andrea] Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, Rodolpho Paulo Rocco 255, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil.
[Carneiro, Jose Vasconcellos Antonio] Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, Rodolpho Paulo Rocco 255, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil.
[Martins, Ivanir] Instituto Nacional de Cancer, Divisao de Patologia, 20230-130 Rio de Janeiro, Brazil.
[de Faria, Antonio Silvestre Paulo] Instituto Nacional de Cancer, Divisao de Patologia, 20230-130 Rio de Janeiro, Brazil.
[Ferreira, Aparecida Maria] Instituto Nacional do Cancer, Secao de Endoscopia Digestiva, 20230-130 Rio de Janeiro, Brazil.
[de Mello, Linhares Riello Eduardo] Instituto Nacional do Cancer, e Secao de Cirurgia Oncologica Abdomino-pelvica, 20230-130 Rio de Janeiro, Brazil.
[Fogaca, Soares Homero] Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, Rodolpho Paulo Rocco 255, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil.
[Elia, Carvalho Siqueira Celeste] Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, Rodolpho Paulo Rocco 255, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil.
[de Souza, Siffert Pereira Heitor] Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, Rodolpho Paulo Rocco 255, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil.
RP de Souza, SPH (reprint author), Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitario Clementino Fraga Filho, Departamento de Clinica Medica, 21941-913 Rio de Janeiro, Brazil.
EM hsouza@hucff.ufrj.br;heitor.souza@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 349
EP 355
DI 10.1007/s12253-010-9333-z
PG 7
ER
PT J
AU Cai, W
Sun, Y
Wang, W
Han, Ch
Ouchida, M
Xia, W
Zhao, X
Sun, B
AF Cai, Wenjuan
Sun, Yan
Wang, Wei
Han, Chunrong
Ouchida, Mamoru
Xia, Wenbin
Zhao, Xiulan
Sun, Baocun
TI The Effect of SYT-SSX and Extracellular Signal-Regulated Kinase (ERK) on Cell Proliferation in Synovial Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Synovial sarcoma; Cell proliferation; Fusion gene
ID Synovial sarcoma; Cell proliferation; Fusion gene
AB The character of Synovial sarcoma is the chromosomal translocation t(X; 18)(p11.2;q11.2), which results in the fusion of the SYT gene with a SSX gene. There is little study that could fully elucidate the mechanism of pathogenesis of this fusion transcript. This study is designed to gain more insight into the function of this fusion gene. We evaluated the whole genome expression in SYO-1 cells inhibited as a result of specific small interfering RNA for SYT-SSX. Cell proliferation and apoptosis were analyzed by flow cytometer and MTT. The proteins correlated with proliferation were also detected using western blot. TUNEL and Immunohistochemical stain assessment were also carried out on TMA of SS tissues. The mRNA level reduced over 90% caused by SYT-SSX specific siRNA. Five pathways were employed, that ERK1/2 pathway was differential significantly (p=0.043218). Meanwhile, down-regulation of SYT-SSX fusion gene expression would inhibit the proliferation of SS cell and the survival rate decreased (34.1%), while apoptotic rate increased (10.92%). After transfected with SYT-SSX-specific siRNA it caused a block in G1/G0 phase (31.99%) of SYO-1 cells compared with control cells. The protein level of ERK1/2, p-ERK, and cyclin D1 altered in same trend with expression of SYT-SSX. In TMA stain assessment, SYT-SSX positive group with high ki-67 LI expressed more cyclin D1and CDK4 than the SYT-SSX negative group. High ki-67 LI was detected in cases with p-ERK expression. Meanwhile, cyclin D1 and CDK4 were shown to be more expressed in tumor cells with p-ERK expression. Our results suggest that the fusion gene SYTSSX should be considered to play important role on SS cell growth via ERK pathway. This study may be valuable for understanding the pathogenic role and molecular mechanism of the fusion gene SYT-SSX in synovial sarcoma through the proposed genome-wide approach. Furthermore, the research would open up the possibility of using SYT-SSX and ERK as a therapeutic target.
C1 [Cai, Wenjuan] Tianjin Medical University, Department of PathologyTianjin, China.
[Sun, Yan] Tianjin Medical University, Department of PathologyTianjin, China.
[Wang, Wei] Tianjin Medical University, Department of PathologyTianjin, China.
[Han, Chunrong] Tianjin Medical University, Department of PathologyTianjin, China.
[Ouchida, Mamoru] Okayama University, Graduate School of Medicine and Dentistry, Department of Molecular GeneticsOkayama, Japan.
[Xia, Wenbin] Tianjin Medical University, Department of PathologyTianjin, China.
[Zhao, Xiulan] Tianjin Medical University, Department of Pathology, 300060 Tianjin, China.
[Sun, Baocun] Tianjin Medical University, Department of PathologyTianjin, China.
RP Sun, B (reprint author), Tianjin Medical University, Department of Pathology, Tianjin, China.
EM baocunsun@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 357
EP 367
DI 10.1007/s12253-010-9334-y
PG 11
ER
PT J
AU Zhao, P
Lu, Y
Liu, L
Zhong, M
AF Zhao, Po
Lu, Yali
Liu, Lin
Zhong, Mei
TI Aberrant Cytoplasmic Expression of Cyclin B1 Protein and its Correlation with EBV-LMP1, P53 and P16(INK4A) in Classical Hodgkin Lymphoma in China
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lymphoma; Cyclin B1; EBV; P53; p16; Immunohistochemistry
ID Lymphoma; Cyclin B1; EBV; P53; p16; Immunohistochemistry
AB The relationships between the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) in Chinese classical Hodgkin lymphoma are unknown and need exploring. Samples of classical Hodgkin lymphoma from 60 Chinese patients were analyzed for the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) proteins by immunohistochemistry. Cyclin B1 protein was overexpressed in 90.0% (54/60) of this group of classical Hodgkin lymphoma, staining mainly and strongly in cytoplasm but also sparsely and weakly in nucleus of the Hodgkin and Reed-Sternberg (HRS) cells. EBV-LMP1, P53 and P16 (INK4A) were overexpressed in 85.0%, 96.7% and 71.7% of Hodgkin lymphoma, respectively. EBV-LMP1, P53 and P16(INK4A) were was noted in the nucleus of HRS cells. Microscopically, cyclin B1 and P53 staining distinguished the HRS cells from the complex background of lymphocytes. Cyclin B1 was positively correlated with EBV-LMP1 (P<0.001) and P53(P<0.001), but was inversely related to P16(INK4A) (P<0.05). It is suggested that overexpression of cyclin B1 could play an important role in the evolution of classical Hodgkin lymphoma, and cyclin B1 may be considered as a potential adjunct marker to identify HRS cells in diagnosis and be served as Hodgkin lymphomaassociated antigen in the near future.
C1 [Zhao, Po] Chinese People’s Liberation Army (PLA) General Hospital, Department of Pathology, 28 Fuxing Road, 100853 Beijing, China.
[Lu, Yali] Chinese People’s Liberation Army (PLA) General Hospital, Department of Pathology, 28 Fuxing Road, 100853 Beijing, China.
[Liu, Lin] Chinese People’s Liberation Army (PLA) General Hospital, Department of Pathology, 28 Fuxing Road, 100853 Beijing, China.
[Zhong, Mei] Chinese People’s Liberation Army (PLA) General Hospital, Department of Pathology, 28 Fuxing Road, 100853 Beijing, China.
RP Zhao, P (reprint author), Chinese People’s Liberation Army (PLA) General Hospital, Department of Pathology, 100853 Beijing, China.
EM zhaopo@301hospital.com.cn
CR Stein H, Delsol G, Pileri S, Said J, Mann R, Poppema S, Jaffe ES, Swerdlow SH, 2001, Classical Hodgkin lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds, World Health Organization classification of tumours—tumours of haematopoeitic and lymphoid tissues, Chapter 8. IARC, Lyon, pp 244– 253
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 369
EP 373
DI 10.1007/s12253-010-9335-x
PG 5
ER
PT J
AU Narita, D
Seclaman, E
Ilina, R
Cireap, N
Ursoniu, S
Anghel, A
AF Narita, Diana
Seclaman, Edward
Ilina, Razvan
Cireap, Natalia
Ursoniu, Sorin
Anghel, Andrei
TI ADAM12 and ADAM17 Gene Expression in Laser-capture Microdissected and Non-microdissected Breast Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ADAM12; ADAM17; Gene expression; Laser-capture microdissection; Breast tumors
ID ADAM12; ADAM17; Gene expression; Laser-capture microdissection; Breast tumors
AB ADAM (a disintegrin and metalloprotease)12 and ADAM17 are multidomain transmembrane proteins involved in ectodomain shedding of cytokines, growth factors and adhesion molecules, with pivotal activities in the tumor microenvironment. The aim of this study was to confirm the up-regulation of ADAM17 and ADAM12 gene splicing variants in breast tumors and to delineate their expression between laser-capture microdissected (LCM) and nonmicrodissected breast tumors. The gene expression was analyzed by quantitative-reverse transcription-PCR in a total sample of 109 breast tumors paired with corresponding nonneoplastic breast tissues. ADAM12 and 17 proteins expression for corresponding tissue samples was confirmed by immunohistochemistry. ADAM12S, 12L and 17 genes were significantly up-regulated in either malign or benign LCM samples when compared to non-tumor controls. For non-LCM samples, it was obtained also an increased expression for ADAM12 and 17 genes in cancers, while in benign tumors only ADAM12 variants were significantly upregulated compared to controls. When benign versus malignant tumors were compared, in LCM samples all investigated genes displayed a higher expression in cancers, whereas in non-LCM, ADAM12 variants were overexpressed in benign samples. The increased expression of ADAM12 protein in the tumor cells and stroma of benign breast diseases was immunohistochemically confirmed. These differences between LCM and non-LCM samples were explained by the contribution of the stroma to the expression of this marker. This study underlines the accuracy conferred by homogenous LCM samples on gene expression profiles and confers further evidence regarding the role of ADAM12 and 17 in the breast tumorigenesis and progression.
C1 [Narita, Diana] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu Square No. 2A, 300041 Timisoara, Romania.
[Seclaman, Edward] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu Square No. 2A, 300041 Timisoara, Romania.
[Ilina, Razvan] University of Medicine and Pharmacy, Department of Surgical OncologyTimisoara, Romania.
[Cireap, Natalia] University of Medicine and Pharmacy, Department of Surgical OncologyTimisoara, Romania.
[Ursoniu, Sorin] University of Medicine and Pharmacy, Department of Public HealthTimisoara, Romania.
[Anghel, Andrei] University of Medicine and Pharmacy, Biochemistry Department, Eftimie Murgu Square No. 2A, 300041 Timisoara, Romania.
RP Narita, D (reprint author), University of Medicine and Pharmacy, Biochemistry Department, 300041 Timisoara, Romania.
EM diana_narita@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 375
EP 385
DI 10.1007/s12253-010-9336-9
PG 11
ER
PT J
AU Yang, L
Bian, Y
Huang, Sh
Ma, X
Zhang, Ch
Su, X
Chen, ZJ
Xie, J
Zhang, H
AF Yang, Ling
Bian, Yuehong
Huang, Shuhong
Ma, Xiaoli
Zhang, Chi
Su, Xiulan
Chen, Zi-Jiang
Xie, Jingwu
Zhang, Hongwei
TI Identification of Signature Genes for Detecting Hedgehog Pathway Activation in Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; Hedgehog; Hedgehoginteracting protein; Platelet derived growth factor receptor alpha; Smoothened; Suppressor of fused
ID Esophageal cancer; Hedgehog; Hedgehoginteracting protein; Platelet derived growth factor receptor alpha; Smoothened; Suppressor of fused
AB The hedgehog signaling pathway plays an important role in cell growth and differentiation both in normal embryonic development and in tumors. Our previous work shows that hedgehog pathway is frequently activated in esophageal cancers. To further elucidate the role of hedgehog pathway in esophageal cancers we examined the expression of the target genes, hedgehog-interacting protein (HIP) and platelet derived growth factor receptor alpha (PDGFRα) and hedgehog signaling molecules, smoothened (SMO), suppressor of fused (Su(Fu)) in the specimens using in-situ hybridization and RT-PCR. We found that HIP, PDGFRα, SMO and Su(Fu) gene highly expressed in the primary esophageal squamous cell carcinomas but not in normal esophageal tissue. The transcripts of HIP, PDGFRα and SMO were expressed in 13 of 15 esophageal cancers. Su(Fu) expression was missing in 2 esophageal cancers. The results from in-situ hybridization were further confirmed by RT-PCR. Our results revealed a set of genes for detecting hedgehog signaling activation in esophageal cancer.
C1 [Yang, Ling] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
[Bian, Yuehong] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
[Huang, Shuhong] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
[Ma, Xiaoli] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
[Zhang, Chi] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
[Su, Xiulan] Inner Mongolia Medical College, 010050 Hohhot, China.
[Chen, Zi-Jiang] Provincial Hospital Affiliated to Shandong University, Reproductive Medical Center, 250021 Jinan, China.
[Xie, Jingwu] Indiana University School of Medicine, Division of hematology and Oncology, Indiana University Simon Cancer Center, Wells Center for Pediatric Research, Department of Pediatrics, 46202 Indianapolis, IN, USA.
[Zhang, Hongwei] Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
RP Zhang, H (reprint author), Shandong University, School of Life Sciences, Institute of Developmental Biology, 250100 Jinan, China.
EM zhw@sdu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 387
EP 391
DI 10.1007/s12253-010-9337-8
PG 5
ER
PT J
AU Baliko, Z
Sarosi, V
Illes, BM
Varga, Zs
Hegedus, G
Molnar, P
Szakall, Sz
AF Baliko, Zoltan
Sarosi, Veronika
Illes, Balazs Miklos
Varga, Zsuzsanna
Hegedus, Geza
Molnar, Peter
Szakall, Szabolcs
TI PET-CT Imaging and Reality
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Chronic necrotizing pulmonary aspergillosis; Immunocompromised state; Metastatising colon neoplasia; PET/CT
ID Chronic necrotizing pulmonary aspergillosis; Immunocompromised state; Metastatising colon neoplasia; PET/CT
AB The spectrum of human diseases caused by members of the Aspergillus genus is extensive. It ranges from allergic reactions to colonization of preexisting pulmonary cavities to invasion and destruction of lung parenchyma with pyemic spread to brain, skin, and other organs, causing rapid death. The immune status of the host is a crucial factor in determining the phenotype and severity of the disease. In this case report Chronic Necrotizing Pulmonary Aspergillosis (CNPA), a rare, locally- or semi-invasive variant of pulmonary Aspergillosis, mimicking lung metastasis is presented. The 60-year-old male patient had earlier received multiple cycles of systemic chemotherapy due to colorectal carcinoma. Our case report focuses on the benefits and the possible disadvantages of PET-CT imaging in CNPA.
C1 [Baliko, Zoltan] Baranya County Hospital, Department of Respiratory Medicine, 2 Rakoczi street, 7623 Pecs, Hungary.
[Sarosi, Veronika] Baranya County Hospital, Department of Respiratory Medicine, 2 Rakoczi street, 7623 Pecs, Hungary.
[Illes, Balazs Miklos] University of Pecs, I. Department of Internal Medicine, 2 Rakoczi street, 7623 Pecs, Hungary.
[Varga, Zsuzsanna] Baranya County Hospital, Department of OncologyPecs, Hungary.
[Hegedus, Geza] County Hospital of Baranya, Department of PathologyPecs, Hungary.
[Molnar, Peter] Szent Imre Hospital, Department of Diagnostic ImagingBudapest, Hungary.
[Szakall, Szabolcs] Szent Imre Hospital, Department of Diagnostic ImagingBudapest, Hungary.
RP Illes, BM (reprint author), University of Pecs, I. Department of Internal Medicine, 7623 Pecs, Hungary.
EM illes.balazs@yahoo.com
CR Soubani AO, Chandrasekar PH, 2002, The clinical spectrum of pulmonary aspergillosis. Chest 121:1988–1999
Gefter W, Weingrad T, Epstein D et al, 1981, “Semi-invasive” pulmonary aspergillosis: a new look at the spectrum of Aspergillus infections of the lung. Radiology 140:313–321
Mandell G, Bennett J, Dolin R, eds,, 1995, Principles and practice of infectious diseases. Churchill—Livingstone
Bohacs A, Kocsis J, Somoskovi A, Meszaros Z, Sapi Z, Tamasi L, Bartfai Z, 2004, Chronic necrotizing pulmonary aspergillosis in an immunocompromised patient. Orvosi Hetilap 145(35): 1811–1815
Pass HI et al, 2005, Lung cancer—principles and practice. Lippincott Williams & Wilkins
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 393
EP 395
DI 10.1007/s12253-010-9299-x
PG 3
ER
PT J
AU Liu, X
Deng, Y
Zhang, X
Mukherjee, R
Huang, W
Zhang, G
Wang, H
Li, X
AF Liu, Xi
Deng, Yuan
Zhang, Xuebin
Mukherjee, Rajarshi
Huang, Wei
Zhang, Guanjun
Wang, Hongyan
Li, Xiaofeng
TI Interdigitating Dendritic Cell Sarcoma Following Adult Liver Transplantation: Case Report and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Adult; Differential diagnosis; Epstein-Barr virus; Interdigitating dendritic cell sarcoma; Liver transplantation; Tacrolimus
ID Adult; Differential diagnosis; Epstein-Barr virus; Interdigitating dendritic cell sarcoma; Liver transplantation; Tacrolimus
AB Interdigitating dendritic cell sarcoma is an extremely rare neoplasm derived from professional antigen presenting cells. We report an unusual case of such a tumor occurring in a 61-year-old woman who had undergone orthotopic liver transplantation for stage IVA2 primary hepatocellular carcinoma with a raised preoperative α-fetoprotein level, followed by tacrolimus-based immunosuppressive therapy. During her subsequent management, the tacrolimus blood levels ranged from 7.9 ng/mL to 16.1 ng/mL. Physical examination revealed bilateral neck and left axillary lymphadenopathy. No evidence of either chronic hepatitis B virus or Epstein-Barr virus could be detected in serum. An excisional biopsy of a right neck lymph node was performed. Microscopically, the normal architecture was diffusely effaced by a proliferation of spindled to ovoid cells arrayed in a fascicular, ill-defined whorled pattern and small lymphocytes were admixed in varying numbers with the tumor cells. Immunohistochemical studies showed that the tumor cells were positive for S100 protein, vimentin and CD68. Based on these findings, the case was diagnosed as an interdigitating dendritic cell sarcoma. The patient unfortunately had no response to 2 cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), and died of wide spread disease 6 months after the original biopsy. We propose that tacrolimus-based immunosuppression was associated with the development of interdigitating dendritic cell sarcoma after liver transplantation in this case.
C1 [Liu, Xi] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Deng, Yuan] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Zhang, Xuebin] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Mukherjee, Rajarshi] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Huang, Wei] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Zhang, Guanjun] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Wang, Hongyan] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Li, Xiaofeng] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
RP Liu, X (reprint author), Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
EM liuxizgq@gmail.com
CR Swerdlow SH, Campo E, Harris NL et al, 2008, WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon
Inaba K, Inaba M, 1999, Cell biologic properties of dendritic cells. Saishinigaku 54:14–21
Fonseca R, Yamakawa M, Nakamura S et al, 1998, Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review. Am J Hematol 59:161–167
Turner RR, Wood GS, Beckstead JH et al, 1984, Histiocytic malignancies: morphologic, immunologic, and enzymatic heterogeneity. Am J Surg Pathol 8:485–500
American Liver Tumor Study Group, 1998, A randomized prospective multi-institutional trial of orthotopic liver transplantation or partial hepatic resection with or without adjuvant chemotherapy for hepatocellular carcinoma. Investigator Booklet and Protocol
Feltkamp CA, van Heerde P, Feltkamp-Vroom TM et al, 1981, A malignant tumor arising from interdigitating cells; light microscopical, ultrastructural, immuno-and enzyme-histochemical characteristics. Virchows Arch A Pathol Anat Histol 393:183–192
Nakamura S, Hara K, Suchi T et al, 1988, Interdigitating cell sarcoma: a morphologic, immunohistologic, and enzymehistochemical study. Cancer 61:562–568
Weiss LM, Berry GJ, Dorfman RF et al, 1990, Spindle cell neoplasms of lymph nodes of probable reticulum cell lineage: true reticulum cell sarcoma? Am J Surg Pathol 14:405–414
Miettinen M, Fletcher CD, Lasota J, 1993, True histiocytic lymphoma of small intestine: analysis of two S-100 proteinpositive cases with features of interdigitating reticulum cells sarcoma. Am J Clin Pathol 100:285–292
Nakamura S, Koshikawa T, Kitoh K et al, 1994, Interdigitating cell sarcoma: a morphologic and immunologic study of lymph node lesions in four cases. Pathol Int 44:374–386
Vasef MA, Zaatari GS, Chan WC et al, 1995, Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three doses. Am J Clin Pathol 104:696–701
Liu SM, Huang PH, Liu JM, 1998, Interdigitating reticulum cell tumor of lymph node: a case report and literature review. Pathol Int 48:974–980
Luk IS, Shek TW, Tang VW et al, 1999, Interdigitating dendritic cell tumor of the testis: a novel testicular spindle cell neoplasm. Am J Surg Pathol 23:1141–1148
Gaertner EM, Tsokos M, Derringer GA et al, 2001, Interdigitating dendritic cell sarcoma: a report of four cases and review of the literature. Am J Clin Pathol 115:589–597
Kawachi K, Nakatani Y, Inayama Y et al, 2002, Interdigitating dendritic cell sarcoma of the spleen: report of a case with a review of the literature. Am J Surg Pathol 26:530–537
Olnes MJ, Nicol T, Duncan M et al, 2002, Interdigitating dendritic cell sarcoma: a rare malignancy responsive to ABVD chemotherapy. Leuk Lymphoma 43:817–821
Dillon KM, Hill CM, Cameron CH et al, 2002, Mediastinal mixed dendritic cell sarcoma with hybrid features. J Clin Pathol 55:791–794
Barwell N, Howatson R, Jackson R et al, 2004, Interdigitating dendritic cell sarcoma of salivary gland associated lymphoid tissue not associated with HHV-8 or EBV infection. J Clin Pathol 57:87–89
Pillay K, Solomon R, Daubenton JD et al, 2004, Interdigitating dendritic cell sarcoma: a report of four paediatric cases and review of the literature. Histopathology 44:283–291
Androulaki A, Giaslakiotis K, Lazaris AC, 2005, Interdigitating dendritic cell sarcoma/tumour of the tonsil. Br J Haematol 131:415
Rupar G, Beham-Schmid C, Galle G et al, 2005, Interdigitating dendritic cell sarcoma of urinary bladder mimicking large intravesical calculus. Urology 66:1109
Kanaan H, Al-Maghrabi J, Linjawi A et al, 2006, Interdigitating dendritic cell sarcoma of the duodenum with rapidly fatal course: a case report and review of the literature. Arch Pathol Lab Med 130:205–208
Sharma M, Ahsan F, Ah-See KW et al, 2006, Interdigitating dendritic cell sarcoma of the parotid gland. J Laryngol Otol 120:244–246
Cossu A, Deiana A, Lissia A et al, 2006, Synchronous interdigitating dendritic cell sarcoma and B-cell small lymphocytic lymphoma in a lymph node. Arch Pathol Lab Med 130:544– 547
Jo S, Babb MJ, Hilsinger RL Jr, 2006, Interdigitating dendritic cell sarcoma of cervical lymph nodes. Arch Otolaryngol Head Neck Surg 132:1257–1259
Nayer H, Murphy KM, Hawkins AL et al, 2006, Clonal cytogenetic abnormalities and BCL2 rearrangement in interdigitating dendritic cell sarcoma. Leuk Lymphoma 47:2651–2654
Boldin I, Brix-Grunwald G, Scarpatetti MM et al, 2008, Interdigitating dendritic cell sarcoma of the eyelid with a rapidly fatal course. Arch Ophthalmol 126:738–740
Feldman AL, Arber DA, Pittaluga S et al, 2008, Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood 111:5433–5439
Lee JC, Christensen T, O’Hara CJ, 2009, Metastatic interdigitating dendritic cell sarcoma masquerading as a skin primary tumor: a case report and review of the literature. Am J Dermatopathol 31:88–93
Kapucuoglu N, Percinel S, Ventura T et al, 2009, Dendritic cell sarcomas/tumours of the breast: report of two cases. Virchows Arch 454:333–339
Adam Z, Pour L, Vesely K et al, 2009, Interdigitating dendritic cell sarcoma of the leg. Onkologie 32:364–365
Efune G, Sumer BD, Sarode VR et al, 2009, Interdigitating dendritic cell sarcoma of the parotid gland: case report and literature review. Am J Otolaryngol 30:264–268
Chen W, Lau SK, Fong D et al, 2009, High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/ dendritic cell sarcomas. Am J Surg Pathol 33:863–873
Fraser CR, Wang W, Gomez M et al, 2009, Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma to interdigitating dendritic cell sarcoma: evidence for transdifferentiation of the lymphoma clone. Am J Clin Pathol 132:928–939
Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R et al, 1995, An increased incidence of Epstein-Barr Virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation 59:524–529
Cacciarelli TV, Reyes J, Jaffe R et al, 2001, Primary tacrolimus, FK506, therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients. Pediatr Transplant 5:359–364
Kairouz S, Hashash J, Kabbara W et al, 2007, Dendritic cell neoplasms: an overview. Am J Hematol 82:924–928
Grogg KL, Macon WR, Kurtin PJ et al, 2005, A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor. Mod Pathol 18:260–266
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 397
EP 402
DI 10.1007/s12253-010-9312-4
PG 6
ER
PT J
AU Mete,
Dogan,
Kapran, Y
Tihan, D
Erbil, Y
Ozarmagan, S
AF Mete, Ozgur
Dogan, Oner
Kapran, Yersu
Tihan, Deniz
Erbil, Yesim
Ozarmagan, Selcuk
TI Intestinal Langerhans Cell Histiocytosis-like Lesion in an Adult Presented with Diverticulitis: A Reactive or Neoplastic Condition?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Langerhans cell histiocytosis; Langerhans cell hyperplasia; Langerhans cell histiocytosis-like lesion; Gastrointestinal tract; Diverticulitis
ID Langerhans cell histiocytosis; Langerhans cell hyperplasia; Langerhans cell histiocytosis-like lesion; Gastrointestinal tract; Diverticulitis
AB The involvement of the gut by Langerhans cell histiocytosis (LCH) is very rare in adults; however this is usually observed with a disseminated disease in children. We report a 75-year-old male patient who underwent right hemicolectomy for a complicated intestinal diverticular disease. The surgical specimen revealed LCH-like proliferative lesion associated with diverticulitis. The overall morphological and immunohistochemical findings are indistinguishable from LCH. Systemic scans and subsequently performed bone marrow biopsies were free of disease. Although the HUMARA clonality assay cannot be assessed, the lack of evidence of LCH progression or disease elsewhere in the whole body strongly supported the possibility of an atypical reactive phenomenon probably due to the underlying intestinal diverticular disease. Therefore, it is important to avoid diagnosing such a unifocal Langerhans cell proliferation as LCH in patients with underlying pathologies in the absence of systemic involvement. Therefore, without knowledge of clonal status of a unifocal Langerhans cell proliferation, we recommend using the terminology of LCH-like lesion.
C1 [Mete, Ozgur] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, CapaIstanbul, Turkey.
[Dogan, Oner] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, CapaIstanbul, Turkey.
[Kapran, Yersu] Istanbul Medical Faculty, Department of Pathology, Temel Bilimler Binasi, CapaIstanbul, Turkey.
[Tihan, Deniz] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Erbil, Yesim] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Ozarmagan, Selcuk] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
RP Mete, (reprint author), Istanbul Medical Faculty, Department of Pathology, Istanbul, Turkey.
EM ozgurmete77@gmail.com
CR Levy J, Khaskelberg A, Garvin J, 2001, Langerhans cell histiocytosis, LCH, involving the gastrointestinal tract: a clinical-electrogastrographic correlation. J Pediatr Gastroenterol Nutr 33:511–514
Santos-Machado TM, Cristofani LM, Almedia MT, Maluf PT, Costa PA, Pereira MA et al, 1999, Disseminated Langerhans cell histiocytosis and massive protein-losing enteropathy. Braz J of Med and Biol Res 32:1095–1099
Egeler RM, Schipper ME, Heymans HS, 1990, Gastrointestinal involvement in Langerhans cell histiocytosis, Histiocytosis X): a clinical report of three cases. Eur J Pediatr 149:325–329
Patel BJ, Chippindale AJ, Gupta SC, 1991, Case report: small bowel histiocytosis-X. Clin Radiol 44:62–63
Terracciano L, Kocher T, Cathomas G, Bubendorf L, Lehmann FS, 1999, Langerhans cell histiocytosis of the stomach with atypical morphological features. Pathol 49:553–556
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds,, 2008, WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon
Merad M, Ginhoux F, Collin M, 2008, Origin, homeostasis and function of Langerhans cells and other langerin expressing dendritic cells. Nat Rev Immunol 8:935–947
Chang SY, Kweon MN, 2010, Langerin-expressing dendritic cells in gut-associated lymphoid tissues. Immunol Rev 234:233–346
Lau SK, Chu PG, Weiss LM, 2008, Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non- Langerhans cell histiocytic disorders. Am J Surg Pathol 32:615– 619
Verdijk P, Dijkman R, Plasmeijer EI, Mulder AA, Zoutman WH, Mieke Mommaas A et al, 2005, A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human langerin gene. J Invest Dermatol 124:714– 717
Kissenpfennig A, Ait-Yahia S, Clair-Moninot V, Stossel H, Badell E, Bordat Y et al, 2005, Disruption of the langerin ⁄ CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol Cell Biol 25:88–99
Negrin-Dastis S, Butenda D, Dorzee J, Fastrez J, D'Odemont JP, 2007, Complete disappearance of lung abnormalities on highresolution computed tomography: a case of histiocytosis X. Can Respir J 14:235–237
Christie LJ, Evans AT, Bray SE, Smith ME, Kernohan NM, Levison DA et al, 2006, Lesions resembling Langerhans cell histiocytosis in association with other lymphoproliferative disorders: a reactive or neoplastic phenomenon? Hum Pathol 37:32–39
Bhattacharjee P, Glusac EJ, 2007, Langerhans cell hyperplasia in scabies: a mimic of Langerhans cell histiocytosis. J Cutan Pathol 34:716–720
Burch JM, Krol A, Weston WL, 2004, Sarcoptes scabiei infestation misdiagnosed and treated as Langerhans cell histiocytosis. Pediatr Dermatol 21:58–62
Singaram C, Sengupta A, Stevens C, Spechler SJ, Goyal RK, 1991, Localization of calcitonin gene-related peptide in human esophageal Langerhans cells. Gastroenterology 100:560–563
Schneider EN, Smoller BR, Lamps LW, 2004, Histiocytic subpopulations in the gastrointestinal tract: distribution and possible relationship to function. Appl Immunohistochem Mol Morphol 12:356–359
Niess JH, Reinecker HC, 2005, Lamina propria dendritic cells in the physiology of the gastrointestinal tract. Curr Opin Gastroenterol 21:687–691
Selim MA, Shea CR. Langerhans cell histiocytosis. eMedicine Specialities, available at http://www.emedicine.com/derm/topic216. htm, last updated 07.02.2007).
Giona F, Caruso R, Testi AM, Moleti ML, Malagnino F, Martelli M et al, 1997, Langerhans cell histiocytosis in adults: a clinical and therapeutic analysis of 11 patients from a single institution. Cancer 80:1786–1791
Choi SW, Bangaru BS, Wu CD, Finlay JL, 2003, Gastrointestinal involvement in disseminated Langerhans cell histiocytosis, LCH, with durable complete response to 2-chlorodeoxyadenosine and high-dose cytarabine. J Pediatr Hematol Oncol 25:503–506
Hait E, Liang M, Degar B, Glickman J, Fox VL, 2006, Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report and literature review. Pediatrics 118:e1593–e1599
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 403
EP 407
DI 10.1007/s12253-010-9313-3
PG 5
ER
PT J
AU Harangi, M
Kovacs, T
Rakoczi,
Rejto, L
Miko, L
Toth, L
Szucs, G
Galuska, L
Paragh, Gy
AF Harangi, Mariann
Kovacs, Tibor
Rakoczi, Eva
Rejto, Laszlo
Miko, Laszlo
Toth, Laszlo
Szucs, Gabriella
Galuska, Laszlo
Paragh, Gyorgy
TI Malignancy or Inflammation? A Case Report of a Young Man with Fever of Unknown Origin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Fever of unknown origin; Chronic osteomyelitis; Vertebral biopsy; Positron emission tomography; Magnetic resonance imaging
ID Fever of unknown origin; Chronic osteomyelitis; Vertebral biopsy; Positron emission tomography; Magnetic resonance imaging
AB A case of a young man with fever of unknown origin is presented. This diagnosis can be frustrating for both patients and physicians because the diagnostic workup often involves numerous noninvasive and invasive procedures that sometimes fail to explain the fever. In the presented case some of the imaging diagnostic findings suggested malignant hematological disorder. However, histopathological and microbiological investigation proved vertebral osteomyelitis caused by Staphylococcus haemolyticus. Diagnosis was established by positron emission tomography, magnetic resonance imaging, and culture and histopathological analysis of a spinal biopsy. 3 months of antibiotic therapy was curative. Biopsy and microbiological investigation may be necessary in patients with fever, back pain and evidence of a spinal lesion on imaging, even if neoplastic disease is suspected.
C1 [Harangi, Mariann] University of Debrecen, Medical and Health Science Center, First Department of Medicine, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kovacs, Tibor] University of Debrecen, Medical and Health Science Center, First Department of Medicine, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Rakoczi, Eva] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Rejto, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Miko, Laszlo] University of Debrecen, Clinical Center, Department of NeurosurgeryDebrecen, Hungary.
[Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Szucs, Gabriella] University of Debrecen, Medical and Health Science Center, Department of RheumatologyDebrecen, Hungary.
[Galuska, Laszlo] University of Debrecen, Medical and Health Science Center, Institute of Nuclear MedicineDebrecen, Hungary.
[Paragh, Gyorgy] University of Debrecen, Medical and Health Science Center, First Department of Medicine, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Paragh, Gy (reprint author), University of Debrecen, Medical and Health Science Center, First Department of Medicine, 4032 Debrecen, Hungary.
EM paragh@hotmail.com
CR Petersdorf RG, Beeson P, 1961, Fever of unexplained origin: report on 100 cases. Medicine, Baltimore, 40:1–30
Roth AR, Basello GM, 2003, Approach to the adult patient with fever of unknown origin. Am Fam Physician 68:2223–2228
Mourad O, Palda V, Detsky AS, 2003, A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med 163:545–551
Zimmerli W, 2010, Clinical practice. Vertebral osteomyelitis. N Engl J Med 362:1022–1029
Gomez-Rodriguez N, Ferreio-Seoane JL, Ibanez-Ruan J, Servillano-Castano J, 1998, Spondylodiscitis cause by Streptococcus equisimilis. Br J Rheumatol 37:1030–1032
Kumar A, Sandoe J, Kumar N, 2005, Three cases of vertebral osteomyelitis caused by Streptococcus dysgalactiae subsp. equisimilis. J Med Microbiol 54:1103–1105
Carragee EJ, 1997, Pyogenic vertebral osteomyelitis. J Bone Joint Surg Am 79:874–880
Gemmel F, Dumarey N, Palestro CJ, 2006, Radionuclide imaging of spinal infections. Eur J Nucl Med Mol Imaging 33:1226–1237
Kwee TC, Basu S, Cheng G, Alavi A, 2010, FDG PET/CT in carcinoma of unknown primary. Eur J Nucl Med Mol Imaging 37:635–644
Sammak B, Abd El Bagi M, Al Shahed M et al, 1999, Osteomyelitis: a review of currently used imaging techniques. Eur Radiol 9:894–900
Hsu CY, Yu CW, Wu MZ et al, 2008, Unusual manifestations of vertebral osteomyelitis: intraosseous lesions mimicking metastases. AJNR Am J Neuroradiol 29:1104–1110
Gentry LO, 1990, Antibiotic therapy for osteomyelitis. Infect Dis Clin North Am 4:485–499
Legrand E, Flipo RM, Guggenbuhl P et al, 2001, Management of nontuberculous infectious discitis. treatments used in 110 patients admitted to 12 teaching hospitals in France. Joint Bone Spine 68:504–509
Bhavan KP, Kirmani N, 2009, Hematogenous vertebral osteomyelitis. Mol Med 106:277–282
Roblot F, Besnier JM, Juhel L et al, 2007, Optimal duration of antibiotic therapy in vertebral osteomyelitis. Semin Arthritis Rheum 36:269–277
Yoon SH, Chung SK, Kim KJ et al, 2010, Pyogenic vertebral osteomyelitis: identification of microorganism and laboratory markers used to predict clinical outcome. Eur Spine J 19:575– 582
Hassoun A, Taur Y, Singer C, 2006, Evaluation of thin needle aspiration biopsy in the diagnosis and management of vertebral osteomyelitis, VO). Int J Infect Dis 10:486–487
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 409
EP 413
DI 10.1007/s12253-010-9315-1
PG 5
ER
PT J
AU Myung, KJ
Jeong, BJ
Han, D
Song, SCh
Moon, JH
Kim, AY
Kim, EJ
Byun, Sj
Kim, HW
Chang, SM
AF Myung, Kyung Jae
Jeong, Bong Ji
Han, Daehee
Song, Sung Chi
Moon, Jong Hyeon
Kim, A Young
Kim, Eun Ji
Byun, Sun-ju
Kim, Ho Woo
Chang, Soo Mee
TI Well-Differentiated Liposarcoma of the Oesophagus: Clinicopathological, Immunohistochemical and Array CGH Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Oesophagus; Well-differentiated liposarcoma; Array comparative genomic hybridization; Chromosome; CDK4; MDM2
ID Oesophagus; Well-differentiated liposarcoma; Array comparative genomic hybridization; Chromosome; CDK4; MDM2
AB Liposarcoma develops extremely rarely in the oesophagus. Microscopically, it exhibits subtle atypia of H&E-stained features. Accordingly, immunohistochemical features and chromosomal alterations are used for its confirmatory diagnosis. However, cytogenetic analysis has not been performed for oesophageal liposarcoma. We studied chromosomal alterations using array comparative genomic hybridization (CGH), as well as endoscopic, radiological, H&E-stained and immunohistochemical features in the oesophageal well-differentiated liposarcoma of a 67-year-old man. Array CGH analysis revealed the presence of high-level amplifications at chromosomal locations 1p12–1q21.2, 12q13.2–12q15 and 12q21.33–12q23.1. At least 29 genes were highly amplified (log2 ratio >2), among which CDK4 and MDM2 were the most highly amplified (log2 ratio >4) and were accepted as major target genes. Moreover, the amplification of AMDHD1, HAL and LTA4H (log2 ratio=3.153) was a novel finding. This case suggests the presence of a characteristic profile of gene amplification in well-differentiated liposarcoma of the oesophagus. The amplified genes may be of pathogenic importance for primary oesophageal well-differentiated liposarcoma.
C1 [Myung, Kyung Jae] Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 425 Shindaebang-dong, Dongjak-gu, 156-707 Seoul, South Korea.
[Jeong, Bong Ji] Seoul National University Boramae Hospital, Department of Internal Medicine, 156-707 Seoul, South Korea.
[Han, Daehee] Catholic University Seoul St. Mary’s Hospital, Department of Radiology, 137-701 Seoul, South Korea.
[Song, Sung Chi] Seoul National University Boramae Hospital, Department of Radiology, 156-707 Seoul, South Korea.
[Moon, Jong Hyeon] Seoul National University Boramae Hospital, Department of Thoracic Surgery, 156-707 Seoul, South Korea.
[Kim, A Young] Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 425 Shindaebang-dong, Dongjak-gu, 156-707 Seoul, South Korea.
[Kim, Eun Ji] Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 425 Shindaebang-dong, Dongjak-gu, 156-707 Seoul, South Korea.
[Byun, Sun-ju] Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 425 Shindaebang-dong, Dongjak-gu, 156-707 Seoul, South Korea.
[Kim, Ho Woo] Seoul National University College of Medicine, Department of Pathology, 110-779 Seoul, South Korea.
[Chang, Soo Mee] Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 425 Shindaebang-dong, Dongjak-gu, 156-707 Seoul, South Korea.
RP Chang, SM (reprint author), Seoul National University College of Medicine, Seoul National University Boramae Hospital, Department of Pathology, 156-707 Seoul, South Korea.
EM meesooch@snu.ac.kr
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Shangary S, Wang S, 2008, Targeting the MDM2-p53 interaction for cancer therapy. Clin Cancer Res 14:5318–5324
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 415
EP 420
DI 10.1007/s12253-010-9322-2
PG 6
ER
PT J
AU Albayrak, M
Balcik, SO
Alan, S
Dincer, LS
Yuksel, KM
Albayrak, A
AF Albayrak, Murat
Balcik, Sahin Ozlem
Alan, Saadet
Dincer, Lutfu Suleyman
Yuksel, Kurt Meltem
Albayrak, Aynur
TI A Rare Cause of Fever, Hepatosplenomegaly, and Thrombocytopenia: Hepatosplenic Gamma/Delta T-Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Albayrak, Murat] Diskapi Yildirim Beyazit Education and Research Hospital, Department of Hematology, Umut Mah. Sembol Sok. 26/5 Seyranbaglari, CankayaAnkara, Turkey.
[Balcik, Sahin Ozlem] Fatih University, Medical School, Department of Hematology, Dizgi Sokak 9/6 Basinevleri, 06120 Ankara, Turkey.
[Alan, Saadet] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Dincer, Lutfu Suleyman] Yeditepe University, Medical School, Department of HematologyIstanbul, Turkey.
[Yuksel, Kurt Meltem] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of HematologyAnkara, Turkey.
[Albayrak, Aynur] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
RP Balcik, SO (reprint author), Fatih University, Medical School, Department of Hematology, 06120 Ankara, Turkey.
EM drozlembalcik@yahoo.com
CR Moleti ML, Testi AM, Giona F et al, 2006, Gamma-delta hepatosplenic T-cell lymphoma. Description of a case with immunophenotypic and molecular follow-up successfully treated with chemotherapy alone. Leuk Lymphoma 47, 2):333–336
Weidman E, 2000, Hepatosplenic T cell Lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia 14:991–997
Belhadj K, Reyes F, Farcet JP et al, 2003, Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood 15;102, 13):4261–4269
Copie-Bergman C, Wotherspoon AC, Norton AJ et al, 1998, True histiocytic Lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases. AmJ Surg Pathol 22:1386–1392
Munir J, Preston G, Polish R, 2004, Case report: a common presentation of a rare disease-hepatosplenic T-cell lymphoma. Hawaii Med J 63(11):341–343
Meulenbeld HJ, Spiering W, Nooijen P et al, 2007, Hepatosplenic gammadelta T-cell lymphoma: a case report. Eur J Intern Med 18, 3):241–243
Jaeger G, Bauer F, Brezinschek R et al, 2008, Hepatosplenic gammadelta T-cell lymphoma successfully treated with a combination of alemtuzumab and cladribine. Ann Oncol 19(5):1025–1026
Gopcsa L, Banyai A, Tamaska J et al, 2002, Hepatosplenic gamma delta T-cell lymphoma with leukemic phase successfully treated with 2-chlorodeoxyadenosine. Haematologia, Budap, 32, 4):519–527
Iannitto E, Barbera V, Quintini G et al, 2002, Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin. Br J Haematol 117(4):995–996
Corazzelli G, Capobianco G, Russo F et al, 2005, Pentostatin, 2′- deoxycoformycin, for the treatment of hepatosplenic gammadelta T-cell lymphomas. Haematologica 90(3):ECR14
Grigg AP, 2001, 2′-Deoxycoformycin for hepatosplenic gammadelta T-cell lymphoma. Leuk Lymphoma 42(4):797–799
Mittal S, Milner BJ, Johnston PW et al, 2006, A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol 76, 6):531–534
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 421
EP 423
DI 10.1007/s12253-010-9324-0
PG 3
ER
PT J
AU Dobi,
Kelemen, Gy
Kaizer, L
Weiczner, R
Thurzo, L
Kahan, Zs
AF Dobi, Agnes
Kelemen, Gyongyi
Kaizer, Laszlo
Weiczner, Roland
Thurzo, Laszlo
Kahan, Zsuzsanna
TI Breast Cancer under 40 Years of Age: Increasing Number and Worse Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Age; Breast cancer; Incidence; Predictive factors; Prognostic factors
ID Age; Breast cancer; Incidence; Predictive factors; Prognostic factors
AB Breast cancer at a relatively young age with a poor prognosis is currently exhibiting an increasing incidence. In a retrospective cohort analysis of early breast cancer cases after surgery from our institutional patient registry, 141 patients aged ≤40 years constituted the younger group, with 300 randomly selected patients aged >40 years as controls. A significant and steady increase was found in the relative number of younger cases during the years 2004–2009. The histological type and grade and the lymph node status of the cancers differed significantly between the two groups, with more aggressive biological behaviour, a more advanced stage and a worse prognosis in the younger group. Half of the cancers in the younger cohort were ER-negative, while two-thirds in the control group were ER-positive. Comparativelymore tumours were PR-positive and HER2-negative in the control group than in the younger group. The rates of triple-negative cases were 25% and 13% in the younger age and the control group, respectively (p=0.026). Significantly higher mastectomy and axillary block dissection rates were observed in the younger age group, and more chemotherapy was administered than in the control group. Our findings demonstrate the significance of breast cancer in cases aged <40 years, and draw attention to the need for appropriate care in these cases.
C1 [Dobi, Agnes] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Kaizer, Laszlo] University of Szeged, Department of PathologySzeged, Hungary.
[Weiczner, Roland] University of Szeged, Department of AnatomySzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Dobi, (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM dobiagnes@gmail.com
CR Agarwal G, Pradeep PV, Aggarwal V et al, 2007, Spectrum of breast cancer in Asian women. World J Surg 31:1031–1040
Brinton LA, Sherman ME, Carreon JD, Anderson WF, 2008, Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst 100:1643–1648
Bouchardy C, Fioretta G, Verkooijen HM et al, 2007, Recent increase of breast cancer incidence among women under the age of forty. Br J Cancer 96:1743–1746
Fredholm H, Eaker S, Frisell J et al, 2009, Breast cancer in young women: poor survival despite intensive treatment. PLoS One 4:e7695
Chung M, Chang HR, Bland KI, Wanebo HJ, 1996, Younger women with breast carcinoma have a poorer prognosis than older women. Cancer 77:97–103
McAree B, O’Donnell ME, Spence A et al, 2010, Breast cancer in women under 40 years of age: A series of 57 cases from Northern Ireland. Breast., DOI 10.1016/j.breast.2009.12.002
Winchester DP, 1996, Breast cancer in young women. Surg Clin North Am 76:279–287
Maggard MA, O’Connell JB, Lane KE et al, 2003, Do young breast cancer patients have worse outcomes? J Surg Res 113:109–113
Fernandopulle SM, Cher-Siangang P, Tan PH, 2006, Breast carcinoma in women 35 years and younger: a pathological study. Pathology 38:219–222
Colleoni M, Rotmensz N, Robertson C et al, 2002, Very young women, <35 years, with operable breast cancer: features of disease at presentation. Ann Oncol 13:273–279
Anders CK, Hsu DS, Breakwater G et al, 2008, Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26:3324–3330
Bori R, Cserni G, 2009, Basal phenotype in breast carcinoma occurring in women aged 35 or younger. Pathol Oncol Res 15:41–45
Cabanes A, Vidal E, Perez-Gomez B et al, 2009, Age-specific breast, uterine and ovarian cancer mortality trends in Spain: Changes from 1980–2006. Cancer Epid 33:169–175
Szekely B, Madaras L, Gy S et al, 2010, A fiatal es idoskori emlorak osszehasonlitasa klinikopathologiai jellemzok alapjan. Magy Onkol 54:19–26
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 425
EP 428
DI 10.1007/s12253-010-9305-3
PG 4
ER
PT J
AU Wang, XX
Fu, L
Li, X
Wu, X
Zhu, Z
Fu, L
Dong, JT
AF Wang, Xin-Xin
Fu, Liya
Li, Xuan
Wu, Xiao
Zhu, Zhengmao
Fu, Li
Dong, Jin-Tang
TI Somatic Mutations of the Mixed-Lineage Leukemia 3 (MLL3) Gene in Primary Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MLL3; Mutation; Single nucleotide polymorphism; Expression; Breast cancer
ID MLL3; Mutation; Single nucleotide polymorphism; Expression; Breast cancer
AB The mixed-lineage leukemia 3 (MLL3) gene, which encodes an important component of a histone H3 lysine 4 methyltransferase complex named the ASC-2- and Mll3-containing complex (ASCOM), has been implicated as a tumor suppressor gene due to its frequent mutations in multiple types of human tumors as well as tumor induction upon targeted inactivation of the gene in mice. The role of MLL3 in breast cancer, however, remains unknown. In this study, we sequenced all 59 exons of MLL3 (14.7 Kb coding sequence) in 38 breast cancers from Chinese women, and found three somatic mutations in two of the cases, including one frameshift mutation (c.2687 ins A) that truncates the majority of the MLL3 protein, and two synonymous mutations. In addition to 24 known single nucleotide polymorphisms (SNPs), 5 novel SNPs were also detected in the 38 women; and interestingly, all the 5 novel SNPs alter amino acid sequences of MLL3 thus could have functional consequences. We also examined the expression of MLL3 mRNA in 30 breast tumors and their matched normal breast tissues. While no associations were found between expression change and clinicopathologic parameters, 40% of the samples showed reduced expression in cancer tissues. These results suggest that mutation of MLL3 plays a role in the development of breast cancer.
C1 [Wang, Xin-Xin] Cancer Hospital of Tianjin Medical University, Department of Breast Cancer Pathology and Research Laboratory, Huan Hu Xi Road, 300060 Tianjin, China.
[Fu, Liya] Cancer Hospital of Tianjin Medical University, Department of Breast Cancer Pathology and Research Laboratory, Huan Hu Xi Road, 300060 Tianjin, China.
[Li, Xuan] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 94 Weijin Road, 300071 Tianjin, China.
[Wu, Xiao] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 94 Weijin Road, 300071 Tianjin, China.
[Zhu, Zhengmao] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 94 Weijin Road, 300071 Tianjin, China.
[Fu, Li] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 94 Weijin Road, 300071 Tianjin, China.
[Dong, Jin-Tang] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 94 Weijin Road, 300071 Tianjin, China.
RP Fu, L (reprint author), Cancer Hospital of Tianjin Medical University, Department of Breast Cancer Pathology and Research Laboratory, 300060 Tianjin, China.
EM fulijyb@hotmail.com
CR Ruault M, Brun ME, Ventura M et al, 2002, MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Gene 284(1–2):73–81
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Stephens P, Edkins S, Davies H et al, 2005, A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nat Genet 37(6):590– 592
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 429
EP 433
DI 10.1007/s12253-010-9316-0
PG 5
ER
PT J
AU Khanmohammadi, M
Bagheri Garmarudi, A
Samani, S
Ghasemi, K
Ashuri, A
AF Khanmohammadi, Mohammadreza
Bagheri Garmarudi, Amir
Samani, Simin
Ghasemi, Keyvan
Ashuri, Ahmad
TI Application of Linear Discriminant Analysis and Attenuated Total Reflectance Fourier Transform Infrared Microspectroscopy for Diagnosis of Colon Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancer; Diagnosis; ATR-FTIR; Chemometrics; LDA
ID Colon cancer; Diagnosis; ATR-FTIR; Chemometrics; LDA
AB Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) microspectroscopy was applied for detection of colon cancer according to the spectral features of colon tissues. Supervised classificationmodels can be trained to identify the tissue type based on the spectroscopic fingerprint. A total of 78 colon tissues were used in spectroscopy studies. Major spectral differences were observed in 1,740–900 cm−1 spectral region. Several chemometric methods such as analysis of variance (ANOVA), cluster analysis (CA) and linear discriminate analysis (LDA) were applied for classification of IR spectra. Utilizing the chemometric techniques, clear and reproducible differences were observed between the spectra of normal and cancer cases, suggesting that infrared microspectroscopy in conjunction with spectral data processing would be useful for diagnostic classification. Using LDA technique, the spectra were classified into cancer and normal tissue classes with an accuracy of 95.8%. The sensitivity and specificity was 100 and 93.1%, respectively.
C1 [Khanmohammadi, Mohammadreza] Imam Khomeini International University, Faculty of Science, Chemistry Department, 34149-1-6818 Qazvin, Iran.
[Bagheri Garmarudi, Amir] Imam Khomeini International University, Faculty of Science, Chemistry Department, 34149-1-6818 Qazvin, Iran.
[Samani, Simin] Qazvin University of Medical Sciences, Pathology DepartmentQazvin, Iran.
[Ghasemi, Keyvan] Imam Khomeini International University, Faculty of Science, Chemistry Department, 34149-1-6818 Qazvin, Iran.
[Ashuri, Ahmad] Imam Khomeini International University, Faculty of Science, Chemistry Department, 34149-1-6818 Qazvin, Iran.
RP Khanmohammadi, M (reprint author), Imam Khomeini International University, Faculty of Science, Chemistry Department, 34149-1-6818 Qazvin, Iran.
EM mrkhanmohammadi@gmail.com
CR Cancer Facts & Figures, 2009, A report by American Cancer Society, accessed at: http://www.cancer.org
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2011
VL 17
IS 2
BP 435
EP 441
DI 10.1007/s12253-010-9326-y
PG 7
ER
PT J
AU Vegso, Gy
Hajdu, M
Sebestyen, A
AF Vegso, Gyula
Hajdu, Melinda
Sebestyen, Anna
TI Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Adoptive T-cell therapy; Early detection; Epstein-Barr virus; Immunosuppression; Lymphoma; Posttransplant lymphoproliferative disorders; Rituximab; Risk factors; Solid organ transplantation; Therapy
ID Adoptive T-cell therapy; Early detection; Epstein-Barr virus; Immunosuppression; Lymphoma; Posttransplant lymphoproliferative disorders; Rituximab; Risk factors; Solid organ transplantation; Therapy
AB Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous disease group of benign and malignant entities. The new World Health Organisation classification introduced in 2008 distinguishes early lesions, polymorphic, monomorphic and classical Hodgkin lymphoma-type PTLD. Based on the time of appearance, early and late forms can be identified. PTLDs are the second most frequent posttransplantation tumors in adulthood, and the most frequent ones in childhood. The incidence varies with the transplanted organ — from 1%–2% following kidney transplantation to as high as 10% following thoracic organ transplantation — due to different intensities in immunosuppression. Immunocompromised state and Epstein-Barr virus (EBV) infection are the two major risk factors. In Europe and the US approximately 85% of PTLDs are of B-cell origin, and the majority are EBV-associated. Symptoms are often unspecific; extranodal, organ manifestations and central nervous system involvement is common. Early lesions respond well to a decrease in immunosuppression. Malignant entities are treated with rituximab, chemotherapy, radiotherapy and surgical therapy. Adoptive T-cell transfer represents a promising therapeutic approach. The prognosis is favorable in early PTLD, and poor in late PTLD. Five-year survival is 30% for high-grade lymphomas. The prognosis of EBV-negative lymphomas is worse. Lowering the risk of PTLD may be achieved by low dose maintenance immunosuppression, immunosuppressive drugs inhibiting cell proliferation, and special immunotherapy (e.g. interleukin-2 inhibitors). Early detection is especially important for high risk — e.g. EBV-negative — patients, where the appearance of EBV-DNA and the increase in its titer may help.
C1 [Vegso, Gyula] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, H-1082 Budapest, Hungary.
[Hajdu, Melinda] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Vegso, Gy (reprint author), Semmelweis University, Department of Transplantation and Surgery, H-1082 Budapest, Hungary.
EM vegso@trans.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 443
EP 454
DI 10.1007/s12253-010-9329-8
PG 12
ER
PT J
AU Diaz Delgado, M
Hernandez Amate, A
Pereira Gallardo, S
Jaramillo, S
Virizuela Echaburu, AJ
Gonzalez-Campora, JR
AF Diaz Delgado, Mario
Hernandez Amate, Alicia
Pereira Gallardo, Sofia
Jaramillo, Sara
Virizuela Echaburu, Antonio Juan
Gonzalez-Campora, J Ricardo
TI Gastrointestinal Stromal Tumors: Morphological, Immunohistochemical and Molecular Changes Associated with Kinase Inhibitor Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Gastrointestinal stromal tumors; GIST; Imatinib mesylate; sunitinib malate; Primary resistance; Secondary resistance; Morphological changes; Molecular changes
ID Gastrointestinal stromal tumors; GIST; Imatinib mesylate; sunitinib malate; Primary resistance; Secondary resistance; Morphological changes; Molecular changes
AB Recurrent or metastatic GISTs are currently treated with kinase inhibitors since they achieves disease control in 70–85% of patients but this response depend on KIT and PDGFRA gene mutation status. We review the morfological and molecular findings associated to kinase inhibitors administration in GISTs based on the literature on Medline and authors’ own experience. The initial response to kinase inhibitors (imatinib mesylate, Gleevec, Novartis) usually is partial and depend on the mutational KIT or PDGFRA state. Amongst patients wih KIT mutations, the best results are achived in those harboring exon 11 (85%) and exon 9 (45%) mutations. GISTs harboring PDGFRA gene mutations generally respond favorably except those involving the Asp842Val mutation. In the absence of KIT/PDGFRA gene mutations, partial response or disease stabilization is reported in 23% and 50% of patients, respectively, and disease progression in 19%. Histological examination of tumors displaying an initial response to imatinib reveals a highly-variable reduction in the number of tumor cells, a decline in the proliferative index, myxohyaline or sclerohyaline stroma, and a varying degree of bleeding and edema, necrosis and cystification. 72% of patients with initial good response to imatinib, display metastases or new nodule growth within an existing clinically-quiescent tumor after 12–36 months of treatment. This secondary resistance is characterized by a number of well-defined morphological and molecular changes. Histologically, the new growths display increased mitotic activity, pleomorphism, an epithelioid or mixed phenotype and persistent KIT expression although more rarely, dedifferentiation and loss of KIT expression (Fig. 4), as well as trans-differentiation into a rhabdomyosarcoma or epithelial phenotype has been reported. Molecularly, 46–67% of patients present additional KIT mutations, generally in the kinase domain (exons 13, 14 and 17) but also in the ATP-binding domain (exons 15,16) of the same allele. Secondary PDGFRA mutations are very rare. Secondary mutations have not been observed in GISTs not harboring KIT/PDGFRA mutations, or in tumors displaying an unusual morphology or loss of CD117 expression. A number of studies highlight the presence of different resistance mutations within different new tumor nodules, as well as the simultaneous development of distinct resistant tumor subclones within a single lesion (acquired polyclonal resistance). Secondary mutation in genes other than KIT/PDGFRA has only been reported in BRAF (Val600Glu).
C1 [Diaz Delgado, Mario] Hospital de Merida, Servicio de Anatomia PatologicaBadajoz, Spain.
[Hernandez Amate, Alicia] Hospital Infanta Cristina, Servicio de Anatomia PatologicaBadajoz, Spain.
[Pereira Gallardo, Sofia] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda. Dr. Fedriani s/n, 41009 Seville, Spain.
[Jaramillo, Sara] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda. Dr. Fedriani s/n, 41009 Seville, Spain.
[Virizuela Echaburu, Antonio Juan] Virgen Macarena University Hospital, Oncology ServiceSeville, Spain.
[Gonzalez-Campora, J Ricardo] Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, Avda. Dr. Fedriani s/n, 41009 Seville, Spain.
RP Gonzalez-Campora, JR (reprint author), Virgen Macarena University Hospital and University of Seville Medical School, Department of Pathology, 41009 Seville, Spain.
EM rcampora@us.es
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 455
EP 461
DI 10.1007/s12253-011-9362-2
PG 7
ER
PT J
AU Bene, L
Falus, A
Baffy, N
Fulop, KA
AF Bene, Laszlo
Falus, Andras
Baffy, Noemi
Fulop, Kristof Andras
TI Cellular and Molecular Mechanisms in the Two Major Forms of Inflammatory Bowel Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Crohn’s disease; Inflammatory bowl disease; Intestinal tract; Ulcerative colitis
ID Crohn’s disease; Inflammatory bowl disease; Intestinal tract; Ulcerative colitis
AB The factors involved in the pathogenesis of Crohn’s disease and ulcerative colitis, the two major types of inflammatory bowel disease (IBD) are summarized. Intestinal antigens composed of bacterial flora along with antigen presentation and impaired mucosal barrier have an important role in the initiation of IBD. The bacterial community may be modified by the use of antibiotics and probiotics. The dentritic cells recognize the antigens by cell surface Toll like receptor and the cytoplasmic CARD/NOD system. The balance between Th1/Th2/Th17 cell populations being the source of a variety of cytokines regulates the inflammatory mechanisms and the clearance of microbes. The intracellular killing and digestion, including autophagy, are important in the protection against microbes and their toxins. The homing process determines the location and distribution of the immune cells along the gut. All these players are potential targets of pharmacological manipulation of disease status.
C1 [Bene, Laszlo] Peterfy Hospital, Department of Internal MedicineBudapest, Hungary.
[Falus, Andras] Semmelweis University, Department of Genetics, Cell and ImmunobiologyBudapest, Hungary.
[Baffy, Noemi] Semmelweis University, Department of Genetics, Cell and ImmunobiologyBudapest, Hungary.
[Fulop, Kristof Andras] Semmelweis University, Department of Genetics, Cell and ImmunobiologyBudapest, Hungary.
RP Falus, A (reprint author), Semmelweis University, Department of Genetics, Cell and Immunobiology, Budapest, Hungary.
EM faland@dgci.sote.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 463
EP 472
DI 10.1007/s12253-011-9397-4
PG 10
ER
PT J
AU You, Q
Wang, Xsh
Fu, Sb
Jin, Xm
AF You, Qi
Wang, Xi-shan
Fu, Song-bin
Jin, Xiao-ming
TI Downregulated Expression of Inhibitor of Growth 4 (ING4) in Advanced Colorectal Cancers: A Non-Randomized Experimental Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal carcinoma; Tumor suppressor gene; ING4; Immunohistochemistry
ID Colorectal carcinoma; Tumor suppressor gene; ING4; Immunohistochemistry
AB Colorectal cancer has a high cure rate if it can be detected early. Identifying and understanding the genes involved may enable early diagnosis and reduce mortality. The aim of our study was to investigate the correlation between the expression of ING4 and the pathological features in patients with colorectal cancer. We assayed ING4 protein expression levels in tumor samples from 97 patients diagnosed with colorectal cancer between January 2001 and January 2002. The patients received no other treatments except surgery. ING4 protein expression was downregulated in adenoma relative to normal mucosa and further reduced in colorectal cancer tissues. Furthermore, the suppression of ING4 expression was also related to the more advanced Dukes’ stages. We observed that ING4 expression levels in patients with lymphatic metastasis were lower than those without metastasis. Together, our results indicate that ING4 play a role in colorectal carcinoma progression.
C1 [You, Qi] The Tumor Hospital of Harbin Medical University, Department of Colorectal Surgery, 150040 Harbin, Heilongjiang Province, China.
[Wang, Xi-shan] The Tumor Hospital of Harbin Medical University, Department of Colorectal Surgery, 150040 Harbin, Heilongjiang Province, China.
[Fu, Song-bin] The Tumor Hospital of Harbin Medical University, Department of Colorectal Surgery, 150040 Harbin, Heilongjiang Province, China.
[Jin, Xiao-ming] The Tumor Hospital of Harbin Medical University, Department of Colorectal Surgery, 150040 Harbin, Heilongjiang Province, China.
RP Wang, Xsh (reprint author), The Tumor Hospital of Harbin Medical University, Department of Colorectal Surgery, 150040 Harbin, China.
EM wxshan1208@yahoo.com.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 473
EP 477
DI 10.1007/s12253-010-9301-7
PG 5
ER
PT J
AU Li, N
Wang, J
Shen, Sh
Bu, X
Tian, X
Huang, P
AF Li, Nan
Wang, Jingmei
Shen, Shanshan
Bu, Xiaodong
Tian, Xiaoqiang
Huang, Peilin
TI Expression of p53, Ki-67 and c-Myc Proteins is Predictive of the Surgical Molecular Margin in Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal carcinoma; Surgical molecular margin; p53; Ki-67; c-Myc
ID Colorectal carcinoma; Surgical molecular margin; p53; Ki-67; c-Myc
AB Surgical resection is the mainstay of treatment for colorectal carcinoma, however, the overall survival is modest due to frequent local recurrence from residual cancer cells after "curative" resection. Therefore, the status of surgical margin (tumor free or positive) has a significant influence on patient’s survival. The difference in molecular profile between mucosa neighboring tumor lesions and remote area (surgical margin) may aid in evaluating resection status. 44 colorectal tumor tissues with corresponding adjacent non-neoplastic mucosa (within 3 cm from tumor tissues), and 110 tumor tissues with corresponding surgical margin mucosa (5 cm from tumor tissues) were randomly collected, fixed in 10% formalin and followed by embedding in paraffin. And the expression of p53, Ki-67 and c-Myc were investigated by tissue microarray (TMA) and immunohistochmistry. The expression of p53, Ki-67 and c-Myc were decreased in both adjacent non-neoplastic mucosa and mucosa of surgical margin, comparing to their expression in corresponding cancer cells. Furthermore, the expression of these proteins in mucosa of remote area (surgical margin) was significantly lower than those adjacent to tumor lesions. The expression of p53, Ki-67 and c-Myc in mucosa can be used as molecular marker for assessing surgical margin status in colorectal carcinoma.
C1 [Li, Nan] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, Dingjia Qiao. 87, 210019 Nanjing, China.
[Wang, Jingmei] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of PathologyNanjing, China.
[Shen, Shanshan] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, Dingjia Qiao. 87, 210019 Nanjing, China.
[Bu, Xiaodong] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, Dingjia Qiao. 87, 210019 Nanjing, China.
[Tian, Xiaoqiang] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, Dingjia Qiao. 87, 210019 Nanjing, China.
[Huang, Peilin] Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, Dingjia Qiao. 87, 210019 Nanjing, China.
RP Huang, P (reprint author), Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Pathology, 210019 Nanjing, China.
EM hplwpp@yahoo.cn
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Zlobec I, Holler S, Tornillo L et al, 2009, Combined histomorphologic and immunohistochemical phenotype to predict the presence of vascular invasion in colon cancer. Dis Colon Rectum 52:1114–1121
Kammerer U, Kapp M, Gassel AM et al, 2001, A new rapid immunohistochemical staining technique using the EnVision antibody complex. J Histochem Cytochem 49:623–630
Kamath A, Helie M, Bifulco CB et al, 2009, Lack of immunohistochemical detection of VEGF in prostate carcinoma. Appl Immunohistochem Mol Morphol 17:227–232
Fu CG, Tominaga O, Nagawa H et al, 1998, Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients. Dis Colon Rectum 41:68–74
Bateman AC, Carr NJ, Warren BF, 2005, The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin? J Clin Pathol 58:426– 428
Goldenberg D, Harden S, Masayesva BG et al, 2004, Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg 130:39–44
van Houten VM, Leemans CR, Kummer JA et al, 2004, Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study. Clin Cancer Res 10:3614–3620
Masasyesva BG, Tong BC, Brock MV et al, 2005, Molecular margin analysis predicts local recurrence after sublobar resection of lung cancer. Int J Cancer 113:1022–1025
Yang B, Gao YT, Du Z et al, 2005, Methylation-based molecular margin analysis in hepatocellular carcinoma. Biochem Biophys Res Commun 338:1353–1358
Kane MF, Loda M, Gaida GM et al, 1997, Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57:808–811
Murad JC, Ribeiro U Jr, Safatle-Ribeiro AVet al, 2007, Evaluation of molecular markers in hepatic metastasis of colorectal adenocarcinoma. Hepatogastroenterology 54:1029–1033
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 479
EP 487
DI 10.1007/s12253-010-9323-1
PG 9
ER
PT J
AU Kadivar, M
Monabati, A
Joulaee, A
Hosseini, N
AF Kadivar, Maryam
Monabati, Ahmad
Joulaee, Azadeh
Hosseini, Niloufar
TI Epstein-Barr Virus and Breast Cancer: Lack of Evidence for an Association in Iranian Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epstein–Barr virus (EBV); Breast carcinoma; Iran; Immunohistochemistry (IHC); Polymerase chain reaction (PCR)
ID Epstein–Barr virus (EBV); Breast carcinoma; Iran; Immunohistochemistry (IHC); Polymerase chain reaction (PCR)
AB Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virusencoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.
C1 [Kadivar, Maryam] Tehran University of Medical Sciences, Hazrat Rasool-e-Akram Hospital, Department of Pathology, Niayesh St, Sattarkhan AveTehran, Iran.
[Monabati, Ahmad] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
[Joulaee, Azadeh] Shahid Beheshti University of Medical Sciences, Department of Breast & General surgeryTehran, Iran.
[Hosseini, Niloufar] Shahid Beheshti University of Medical SciencesTehran, Iran.
RP Kadivar, M (reprint author), Tehran University of Medical Sciences, Hazrat Rasool-e-Akram Hospital, Department of Pathology, Tehran, Iran.
EM dmkadivar@gmail.com
CR Labrecque LG, Barnes DM, Fentiman IS et al, 1995, Epstein-Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res 55:39–45
Parkin DM, Bray FI, Devesa SS, 2001, Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):54–66
He J-R, Song Er-Wei, Ren Ze-Fang, 2009, Research advancement on relationship between Epstein-Barr virus and breast cancer. Chin J Cancer 28(8):1–6
Fawzy S, Sallam M, Awad NM, 2008, Detection of Epstein-Barr virus in breast carcinoma in Egyptian women. Clin Biochem 41, 7–8):486–492
Joshi D, Quadri M, Gangane N et al, 2009, Association of Epstein-Barr virus infection with breast cancer in rural Indian women. PLoS One 4 4(12):e8180
Kallkan A, Ozdarendeli A, Bulut Y et al, 2005, Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin-embedded breast cancer tissues. Med Princ Pract 14(4):268–271
Cox B, Richardson A, Graham P et al, 2010, Breast cancer, cytomegalovirus and Epstein-Barr virus: a nested case-control study. Br J Cancer 102(11):1665–1669
Bonnet M, Guinebretiere J, Kremmer E et al, 1999, Detection of EBV DNA by polymerase chain reaction in invasive breast cancers. J Natl Cancer Inst 91:1376–1381
Saito I, Servenius B, Compton T et al, 1989, Detection of EBV DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren’s syndrome. J Exp Med 169:2191– 2198
Horiuchi K, Mishima K, Ohsawa M et al, 1994, Carcinoma of stomach and breast with lymphoid stroma: localisation of Epstein-Barr virus. J Clin Pathol 47:538–540
Luqmani YA, Shousha S, 1995, Presence of Epstein-Barr virus in breast carcinoma. Int J Oncol 6:899–903
Brink AA, van den Brule AJ, van Diest P et al, 2000, Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 92:655–656
Fina F, Romain S, Ouafik L et al, 2001, Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas. Br J Cancer 84:783–790
Grinstein S, Preciado MV, Gattuso P et al, 2002, Demonstration of Epstein-Barr virus in carcinomas of various sites. Cancer Res 62:4876–4878
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Lespagnard L, Cochaux P, Larsimont D et al, 1995, Absence of Epstein-Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction. Am J Clin Pathol 103:449–452
Chu JS, Chen CC, Chang KJ, 1998, In situ detection of Epstien-Barr virus in breast cancer. Cancer Lett 124:53–57
Arbach H, Viglasky V, Lefeu F et al, 2006, Epstein-Barr virus, EBV, genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel, Taxol). J Virol 80:845–853
Perkins RS, Sahm K, Marando C et al, 2006, Analysis of Epstein-Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR. Breast Cancer Res 8(6):R70
Glaser SL, Hsu JL, Gulley ML, 2004, Epstein-Barr Virus and Breast Cancer: State of the Evidence for Viral Carcinogenesis. Cancer Epidemiol Biomark Prev 13:688–697
McCall SA, Lichy JH, Bijwaard KE et al, 2001, Epstein-Barr virus detection in ductal carcinoma of the breast. J Natl Cancer Inst 93:148–150
Deshpande CG, Badve S, Kidwai N et al, 2002, Lack of expression of the Epstein-Barr Virus, EBV, gene products, EBERs, EBNA1, LMP1, and LMP2A, in breast cancer cells. Lab Invest 82:1193–1199
Chu PG, Chang KL, Chen YY et al, 2001, No significant association of Epstein-Barr virus infection with invasive breast carcinoma. Am J Pathol 159:571–578
Chang KL, Albujar PF, Chen YY et al, 1993, High prevalence of Epstain-Barr virus in the reed-sternberg cells of Hodgkin’s disease occurring in Peru. Blood 81:496–501
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 489
EP 492
DI 10.1007/s12253-010-9325-z
PG 4
ER
PT J
AU Kim, SN
Kang, YJ
Jo, JO
Kim, YH
Oh, RY
Kim, YO
Jung, HM
Ock, SM
Cha, HJ
AF Kim, Soo Nam
Kang, Yun-Jeong
Jo, Jin-Ok
Kim, Yeol Heung
Oh, Rim Young
Kim, Young-Ok
Jung, Hyung Min
Ock, Sun Mee
Cha, Hee-Jae
TI Elevated Expression of Thymosin β4, Vascular Endothelial Growth Factor (VEGF), and Hypoxia Inducible Factor (HIF)-1α in Early-Stage Cervical Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Thymosin β4; VEGF; HIF-1α; Angiogenesis
ID Cervical cancer; Thymosin β4; VEGF; HIF-1α; Angiogenesis
AB Recent studies have shown that thymosin β4 (TB-4) is highly related with tumor metastasis and angiogenesis. In addition, TB-4 induced the expression of VEGF in melanoma cells. We investigated the expression patterns of TB-4 and related angiogenic proteins, VEGF, and HIF-1α, at various stages of cervical cancers and also identified the expression pattern of these proteins in metastatic cervical cancers. Expression patterns of TB-4, VEGF, and HIF-1α were studied with tissue microarray containing 42 samples of cervical cancers. In addition, 15 cervical cancers and metastatic tumors in lymph nodes from patients who have metastatic tumors were also analyzed to confirm the role of TB-4, VEGF, and HIF -1α in cervical cancer metastasis. The expression levels of TB-4, VEGF, and HIF-1α were very weak at early cancer stages (stages 0 to 1A) but significantly increased at stage 1B. The numbers of blood vessels in tumors were also increased at stage 1B. The expression patterns of TB-4, VEGF, and HIF-1α were compared in tumors without lymph node metastasis, primary tumors with lymph node metastasis, and metastatic tumors in lymph nodes. The expression levels of TB-4, VEGF, and HIF-1α in primary tumors with lymph node metastasis and their metastatic tumors in lymph node were less than in tumors without lymph node metastasis. These data suggest that TB-4, VEGF, and HIF-1α triggered angiogensis and tumor invasiveness to surrounding tissues at early stage of cervical carcinoma but have a negative or no effect on the metastatic potential.
C1 [Kim, Soo Nam] Kosin University College of Medicine, Department of Obstetrics and GynecologyBusan, South Korea.
[Kang, Yun-Jeong] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Jo, Jin-Ok] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Kim, Yeol Heung] Kosin University College of Medicine, Department of Obstetrics and GynecologyBusan, South Korea.
[Oh, Rim Young] Kosin University College of Medicine, Department of Obstetrics and GynecologyBusan, South Korea.
[Kim, Young-Ok] Kosin University College of Medicine, Department of PathologyBusan, South Korea.
[Jung, Hyung Min] Kyung Hee University, College of Medicine, Department of Obstetrics and GynecologySeoul, South Korea.
[Ock, Sun Mee] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Cha, Hee-Jae] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
RP Cha, HJ (reprint author), Kosin University College of Medicine, Department of Parasitology and Genetics, 602-703 Busan, South Korea.
EM hcha@kosin.ac.kr
CR Low TL, Hu SK, Goldstein AL, 1981, Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces deoxynucleotidy l transferase activity in thymocyte populations. Proc Natl Acad Sci USA 78:1162–1166
Low TL, Goldstein AL, 1985, Thymic hormones: an overview. Methods Enzymol 116:213–219
Safer D, Nachmias VT, 1994, Beta thymosins as actin binding peptides. BioEssays 16:473–479
Yu FX, Lin SC, Morrison-Bogorad M et al, 1993, Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins. J Biol Chem 268:502–509
Yu FX, Lin SC, Morrison-Bogorad M et al, 1994, Effects of thymosin beta 4 and thymosin beta 10 on actin structures in living cells. Cell Motil Cytoskeleton 27:13–25
Grant DS, Rose W, Yaen C et al, 1999, Thymosin beta 4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 3:125–135
Philp D, Goldstein AL, Kleinman HK, 2004, Thymosin beta 4 promotes angiogenesis, wound healing and hair follicle development. Mech Ageing Dev 125:113–115
Philp D, St-Surin S, Cha HJ et al, 2007, Thymosin beta 4 induces hair growth via stem cell migration and differentiation. Ann NY Acad Sci 1112:95–103
Iguchi K, Usami Y, Hirano K et al, 1999, Decreased thymosin beta 4 in apoptosis induced by a variety of antitumor drugs. Biochem Pharmacol 57:1105–1111
Niu M, Nachmias VT, 2007, Increased resistance to apoptosis in cells overexpressing thymosin beta four: a role for focal adhesion kinase pp 125FAK. Cell Adhes Commun 7:311–320
Young JD, Lawrence AJ, MacLean AG et al, 1999, Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med 5:1424– 1427
Cha HJ, Jeong MJ, Kleinman HK, 2003, Role of thymosin beta 4 in tumor metastasis and angiogenesis. J Natl Cancer Inst 95:1674– 1680
Kobayashi T, Okada F, Fujii N et al, 2002, Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. Am J Pathol 160:869–882
Wang WS, Chen PM, Hsiao HL et al, 2004, Overexpression of the thymosin beta-4 gene is associated with increased invasion of SW480 colon carcinoma cells and the distant metastasis of human colorectal carcinoma. Oncogene 23:6666–6671
Huang HC, Hu CH, Tang MC et al, 2007, Thymosin beta 4 triggers an epithelial-mesenchymal transition in colorectal carcinoma by upregulating integrin-linked kinase. Oncogene 26:2781– 2790
Larsson LI, Holck S, 2007, Localization of thymosin beta-4 in tumors. Ann NY Acad Sci 1112:317–325
Larsson LI, Holck S, 2007, Occurrence of thymosin beta 4 in human breast cancer cells and in other cell types of the tumor microenvironment. Hum Pathol 38:114–119
Ji P, Diederichs S, Wang W et al, 2003, MALAT-1, a novel noncoding RNA, and thymosin beta 4 predict metastasis and survival at early-stage non-small cell lung cancer. Oncogene 22:8031–8041
Jia YT, Li ZX, Liu M et al, 2009, Endostar reduces the growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer. Zhonghua Zhong Liu Za Zhi 31:254–257
Willmott LJ, Monk BJ, 2009, Cervical cancer therapy: current, future and anti-angiogensis targeted treatment. Expert Rev Anticancer Ther 9:895–903
Clark EA, Golub TR, Lander ES et al, 2000, Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406:532–535
Otto AM, Mqller CSG, Huff T et al, 2002, Chemotherapeutic drugs change actin skeleton organization and the expression of betathymosins in human breast cancer cells. J Cancer Res Clin Oncol 128:247–256
Yamamoto T, Gotoh M, Kitajima M et al, 1993, Thymosin beta-4 expression is correlated with metastatic capacity of colorectal carcinomas. Biochem Biophys Res Commun 193:706– 710
Monk BJ, Willmott LJ, Sumner DA, 2010, Anti-angiogenesis agents in metastatic or recurrent cervical cancer. Gynecol Oncol 116:181–186
Goncharuk IV, Vorobjova LI, Lukyanova NYet al, 2009, Vascular endothelial growth factor exression in uterine cervical cancer: correlation with clinicopathologic characteristics and survival. Exp Oncol 31:179–181
No JH, Jo H, Kim SH et al, 2009, Expression of vascular endothelial growth factor and hypoxia inducible factor-1alpha in cervical neoplasia. Ann NY Acad Sci 1171:105–110
Sosne G, Szliter EA, Barrett R et al, 2002, Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res 74:293–299
Sosne G, Qiu P, Christopherson PL et al, 2007, Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res 48:663–669
Badamchian M, Fagarasan MO, Danne RL et al, 2003, Thymosin beta 4 reduces lethality and downregulates inflammatorymediators in endotoxin-induced septic shock. Int Immunopharmacol 3:1225–1233
Falk V, Lundgren N, Quarfordt L et al, 1982, Primary surgical treatment of carcinoma stage I of the uterine cervix. Acta Obstet Gynecol Scand 61:481–486
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 493
EP 502
DI 10.1007/s12253-010-9327-x
PG 10
ER
PT J
AU Toth, K
Galamb, O
Spisak, S
Wichmann, B
Sipos, F
Valcz, G
Leiszter, K
Molnar, B
Tulassay, Zs
AF Toth, Kinga
Galamb, Orsolya
Spisak, Sandor
Wichmann, Barnabas
Sipos, Ferenc
Valcz, Gabor
Leiszter, Katalin
Molnar, Bela
Tulassay, Zsolt
TI The Influence of Methylated Septin 9 Gene on RNA and Protein Level in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; mRNA expression; Peripheral blood; Protein expression; Septin 9
ID Colorectal cancer; mRNA expression; Peripheral blood; Protein expression; Septin 9
AB Colorectal cancer is one of the leading death causes in the world. Specificity and sensitivity of the present screening methods are unsuitable and their compliance is too low. Nowadays the most effective method is the colonoscopy, because it gives not only macroscopic diagnosis but therapeutic possibility as well, however the compliance of the patients is very low. Hence development of new diagnostic methods is needed. Altered expression of septin 9 was found in several tumor types including colorectal cancer. The aim of this study was to detect the methylation related mRNA and protein expression changes of septin 9 in colorectal adenomadysplasia-carcinoma sequence and to analyze its reversibility by demethylation treatment. Septin 9 protein expression showed significant difference between normal and colorectal cancer (CRC) samples (p<0,001). According to biopsy microarray results, septin 9 mRNA expression decreased in the progression of colon neoplastic disease (p<0,001). In laser microdissected epithelial cells, septin 9 significantly underexpressed in CRC compared to healthy controls (p<0,001). The expression of septin9_v1 region was higher in the healthy samples, while septin9_v2, v4, v4*, v5 overexpression were detected in cancer epithelial cells compared to normal. The septin 9 mRNA and protein levels of HT29 cells increased after demethylation treatment. The increasing methylation of septin 9 gene during colorectal adenomadysplasia-carcinoma sequence progression is reflected in the decreasing mRNA and protein expression, especially in the epithelium. These changes can be reversed by demethylation agents converting this screening marker gene into therapeutic target.
C1 [Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Spisak, Sandor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Wichmann, Barnabas] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Valcz, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Leiszter, Katalin] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
RP Toth, K (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM drtothkinga@yahoo.com
CR Boyle P, Ferlay J, 2005, Cancer incidence and mortality in Europe, 2004. Ann Oncol 16:481–488
Jemal A, Murray T, Ward E et al, 2005, Cancer statistics, 2005. CA Cancer J Clin 55:10–30
Ebert MP, Model F, Mooney S et al, 2006, Aristaless-like homeobox-4 gene methylation is a potential marker for colorectal adenocarcinomas. Gastroenterology 131:1418–1430
Lofton-Day C, Model F, Devos T et al, 2008, DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem 54:414–423
Grutzmann R, Molnar B, Pilarsky C et al, 2008, Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS ONE 3:e3759
Devos T, Tetzner R, Model F et al, 2009, Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 55:1337–1346
Scott M, Hyland PL, McGregor G et al, 2005, Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours. Oncogene 24:4588–4700
Galamb O, Gyorffy B, Sipos F, 2008, Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 25:1–16
Hall PA, Russell SE, 2004, The pathobiology of the septin gene family. J Pathol 204:489–505
Russell SE, McIlhatton MA, Burrows JF, 2000, Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors. Cancer Res 60:4729–4734
Kalikin LM, Sims HL, Petty EM, 2000, Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene, MSF, that map to a 17q25 region of loss in breast and ovarian tumors. Genomics 63:165–172
Burrows JF, Chanduloy S, McIlhatton MA et al, 2003, Altered expression of the septin gene, SEPT9, in ovarian neoplasia. J Pathol 201:581–588
Montagna C, LyuMS, Hunter K et al, 2003, The Septin 9, MSF, gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187
Tatsumi K, Taki T, Taniwaki M et al, 2001, The CDCREL1 gene fused to MLL in de novo acute myeloid leukemia with t(11;22,, q23;q11.2, and its frequent expression in myeloid leukemia cell lines. Genes Chromosom Cancer 30:230–235
Kim HJ, Ki CS, Park Q et al, 2003, MLL/SEPTIN6 chimeric transcript from invins(X;11)(q24;q23q13, in acute monocytic leukemia: report of a case and review of the literature. Genes Chromosom Cancer 38:8–12
Kojima K, Sakai I, Hasegawa A et al, 2004, FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23). Leukemia 18:998–1005
Tanaka M, Tanaka T, Matsuzaki S et al, 2003, Rapid and quantitative detection of human septin family Bradeion as a practical diagnostic method of colorectal and urologic cancers. Med Sci Monit 9:61–68
Kim DS, Hubbard SL, Peraud A et al, 2004, Analysis of mammalian septin expression in human malignant brain tumors. Neoplasia 6:168–178
Model F, Osborn N, Ahlquist D et al, 2007, Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease. Mol Cancer Res 5:153–163
Toth K, Galamb O, Spisak S et al, 2009, Free circulating DNA based colorectal cancer screening from peripheral blood: the possibility of the methylated septin 9 gene marker. Orv Hetil 150:969–977
Scott M, McCluggage WG, Hillan KJ et al, 2006, Altered patterns of transcription of the septin 9 gene, SEPT9, in ovarian tumorigenesis. Int J Cancer 118:1325–1329
Montagna C, Lyu MS, Hunter K, 2003, The Septin 9, MSF, gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187
Gonzalez ME, Peterson EA, Privette LM, 2007, High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. Cancer Res 67:8554–8564
Liu ZJ, Wang G, Cai Y, 2009, Androgen receptor CpG island methylation status in human leukemia cancer cells. Cancer Investig 27:156–162
Yap OW, Bhat G, Liu L et al, 2009, Epigenetic modifications of the Estrogen receptor beta gene in epithelial ovarian cancer cells. Anticancer Res 29:139–144
Deng G, Kakar S, Okudiara K et al, 2009, Unique methylation pattern of oncostatin m receptor gene in cancers of colorectum and other digestive organs. Clin Cancer Res 15:1519–1526
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 503
EP 509
DI 10.1007/s12253-010-9338-7
PG 7
ER
PT J
AU Halon, A
Materna, V
Drag-Zalesinska, M
Nowak-Markwitz, E
Gansukh, T
Donizy, P
Spaczynski, M
Zabel, M
Dietel, M
Lage, H
Surowiak, P
AF Halon, Agnieszka
Materna, Verena
Drag-Zalesinska, Malgorzata
Nowak-Markwitz, Ewa
Gansukh, Tserenchunt
Donizy, Piotr
Spaczynski, Marek
Zabel, Maciej
Dietel, Manfred
Lage, Hermann
Surowiak, Pawel
TI Estrogen Receptor Alpha Expression in Ovarian Cancer Predicts Longer Overall Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Estrogen receptor alpha; Ovarian cancer; Immunohistochemistry; Cisplatin
ID Estrogen receptor alpha; Ovarian cancer; Immunohistochemistry; Cisplatin
AB Estrogen as a potential factor of ovarian carcinogenesis, acts via two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), but the cellular signal pathways involved are not completely clear so far. In this study we have described the expression of ERα, detected by immunocytochemistry in 11 ovarian carcinoma cell lines and by immunohistochemistry in 43 Federation Internationale des Gyneacologistes et Obstetristes stage III ovarian carcinoma specimens prepared before and after treatment with cisplatin-based schemes. For cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma, analysis of cisplatin sensitivity in 11 ovarian carcinoma cell line was also performed. The strong nuclear ERα expression was only shown in the single A2780P cell line. Expression of ERα in tissue specimens did not reveal any correlations between histopathological parameters (histologic type and grading). We demonstrated a significant association with ERα expression in specimens from primary laparotomies (PL) and cause–specific survival. In the cases terminated by death of the patient, overall immunoreactivity score of ERα expression at PL was significantly lower than in surviving patients. In addition, Kaplan-Meier analysis revealed significantly shorter overall survival time and progression-free time in cases with lower immunoreactivity score of ERα expression at PL. Our findings support the hypothesis that aberrant hormone activity, by way of altered receptor expression, might be an important factor in the malignant transformation of ovarian cancer.
C1 [Halon, Agnieszka] Wroclaw Medical University, Department of Pathology, ul. Marcinkowskiego 1, 50-367 Wroclaw, Poland.
[Materna, Verena] Charite University Hospital, Institute of Pathology, Chariteplatz. 1 20/21, 10117 Berlin, Germany.
[Drag-Zalesinska, Malgorzata] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-356 Wroclaw, Poland.
[Nowak-Markwitz, Ewa] Poznan University of Medical Sciences, Cathedral of Mother’s and Child’s Health, ul. Polna 33, 60-535 Poznan, Poland.
[Gansukh, Tserenchunt] Medical Research Institute of Mongolia, Bayangol duureg, Ard-Ayush Street-1, 210526 Ulan Bator, Mongolia.
[Donizy, Piotr] Wroclaw Medical University, Department of Pathology, ul. Marcinkowskiego 1, 50-367 Wroclaw, Poland.
[Spaczynski, Marek] Poznan University of Medical Sciences, Cathedral of Mother’s and Child’s Health, ul. Polna 33, 60-535 Poznan, Poland.
[Zabel, Maciej] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-356 Wroclaw, Poland.
[Dietel, Manfred] Charite University Hospital, Institute of Pathology, Chariteplatz. 1 20/21, 10117 Berlin, Germany.
[Lage, Hermann] Charite University Hospital, Institute of Pathology, Chariteplatz. 1 20/21, 10117 Berlin, Germany.
[Surowiak, Pawel] Charite University Hospital, Institute of Pathology, Chariteplatz. 1 20/21, 10117 Berlin, Germany.
RP Halon, A (reprint author), Wroclaw Medical University, Department of Pathology, 50-367 Wroclaw, Poland.
EM ahalon2@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 511
EP 518
DI 10.1007/s12253-010-9340-0
PG 8
ER
PT J
AU Fernandez-Acenero, JM
Cordova, Sh
Manzarbeitia, F
Medina, C
AF Fernandez-Acenero, Jesus Maria
Cordova, Sharon
Manzarbeitia, Felix
Medina, Camino
TI Immunohistochemical Profile of Urothelial and Small Cell Carcinomas of the Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urothelial cell carcinoma; Small cell carcinoma; Neuroendocrine tumors; TTF-1; Immunohistochemistry
ID Urothelial cell carcinoma; Small cell carcinoma; Neuroendocrine tumors; TTF-1; Immunohistochemistry
AB Small cell carcinoma of the bladder is an uncommon and rather aggressive bladder tumor, representing less than 1% of all vesical tumors. Small cell carcinoma of different organs has been shown to express markers of neuroendocrine differentiation, and also thyroid transcription factor 1 (TTF-1). TTF-1 is a transcription factor and its expression has been shown mainly in pulmonary small cell carcinomas and adenocarcinomas and in thyroid tumors. Although it was initially proposed as a useful marker to delineate the origin of metastatic adenocarcinomas from the lung, its expression is being increasingly reported in tumors from different origins. The goal of this review is to analyse the immunohistochemical profile of small cell carcinoma of the bladder and to compare it to classical urothelial cell carcinomas. With this aim we have reviewed the small cell bladder carcinomas diagnosed in a single tertiary hospital in Madrid (Fundacion Jimenez Diaz) in the last 12 years. We have found 6 pure small cell carcinomas and performed a wide panel of immunohistochemistry, including cytokeratins 7 and 20, enolase, chromogranin, synaptophysin, CD56 and TTF-1 to these tumors and also to 30 high grade urothelial cell carcinomas of usual type. Only one of our small cell carcinoma cases showed positivity for TTF-1, while five expressed CD56 and four neuron-specific enolase. None of our cases expressed cytokeratin 20 or 7. To our surprise we found a case of conventional urothelial cell carcinoma expressing focally TTF-1. These results are in accordance with the current literature, although our rate of TTF-1 expression (16.6%) is on the low end of the spectrum.
C1 [Fernandez-Acenero, Jesus Maria] University Hospital Fundacion Jimenez Diaz, Department of PathologyMadrid, Spain.
[Cordova, Sharon] University Hospital Fundacion Jimenez Diaz, Department of PathologyMadrid, Spain.
[Manzarbeitia, Felix] University Hospital Fundacion Jimenez Diaz, Department of PathologyMadrid, Spain.
[Medina, Camino] University Hospital Fundacion Jimenez Diaz, Department of PathologyMadrid, Spain.
RP Fernandez-Acenero, JM (reprint author), University Hospital Fundacion Jimenez Diaz, Department of Pathology, Madrid, Spain.
EM mgg10167@gmail.com
CR Blomjous CE, Vos W, De Voogt HJ, Van der Valk P, 1989, Small cell carcinoma of the urinary bladder. A clinicopathological, morphometric, immunohistochemical and ultrastructural series of 18 cases. Cancer 64:1347–1357
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Cheng L, Jones TD, McCarthy RP, Eble JN, Wang M, MacLennan GT, Lopez-Beltran A, Yang XJ, Koch MO, Zhang S, Pan CX, Baldridge LA, 2005, Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma. Am J Pathol 166:1533–1539
Jones TD, Kernek KM, Yang XJ, Lopez-Beltran A, MacLennan GT, Eble JN, Lin H, Pan CX, Tretiakova M, Baldridge LA, Cheng L, 2005, Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases. Hum Pathol 36:718–723
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 519
EP 523
DI 10.1007/s12253-010-9341-z
PG 5
ER
PT J
AU Fotovati, A
Abu-Ali, S
Kage, M
Shirouzu, K
Yamana, H
Kuwano, M
AF Fotovati, Abbas
Abu-Ali, Samah
Kage, Masayoshi
Shirouzu, Kazuo
Yamana, Hideaki
Kuwano, Michihiko
TI N-myc Downstream-regulated Gene 1 (NDRG1) a Differentiation Marker of Human Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Differentiation; Cancer biomarkers; NDRG1; Cap43; Anticancer differentiation therapy
ID Breast cancer; Differentiation; Cancer biomarkers; NDRG1; Cap43; Anticancer differentiation therapy
AB N-myc downstream-regulated gene 1 (NDRG1), also called differentiation-related gene-1 (Drg1) and Cap43, is expressed in various normal tissues and suppressed in several malignancies. In this study, whether NDRG1 expression was correlated with differentiation of human breast cancer cells has been investigated. Endogenous expression level of NDRG1 was closely correlated with differentiation status of breast cancer cell lines. Furthermore, sodium butyrate (NaB), an inducer of cellular differentiation, increased the expression of β-casein, a milk-related differentiation marker, together with upregulation of NDRG1 in breast cancer cells. In contrast, inhibition of NDRG1 by its siRNA resulted in reduced accumulation of β-casein. Immunohistochemical analysis showed co-expression of NDRG1 and β-casein or milk fat protein (MFP), another differentiation marker of breast tissue, in the mouse xenograft model of breast cancer. Furthermore, overexpression of NDRG1 expanded the differentiated area in the xenograft model of breast cancer. In human breast cancer, using samples from 45 patients, we also showed close relationship between NDRG1 and β-casein or MFP expression. Altogether, in vitro and in vivo data demonstrated a possible role of NDRG1 in differentiation of breast cancer. We concluded that NDRG1 could be used as a biomarker for differentiation of breast cancer for both diagnostic and therapeutic purposes.
C1 [Fotovati, Abbas] Kurume University, Institute of Cancer Innovative Therapy, Laboratory of Molecular SurgeryKurume, Japan.
[Abu-Ali, Samah] JOYUP Bio-Medicals, Laboratory of Biomedical Research, Nishi-Ogi-Minami Suginami-kuTokyo, Japan.
[Kage, Masayoshi] Kurume University, Institute of Cancer Innovative Therapy, Laboratory of Molecular SurgeryKurume, Japan.
[Shirouzu, Kazuo] Kurume University, School of Medicine, Kurume University Hospital, Department of SurgeryKurume, Japan.
[Yamana, Hideaki] Kurume University, School of Medicine, Kurume University Hospital, Department of SurgeryKurume, Japan.
[Kuwano, Michihiko] Kyushu University, Graduate School of Pharmaceutical Sciences, Department of PharmaceuticsFukuoka, Japan.
RP Fotovati, A (reprint author), Kurume University, Institute of Cancer Innovative Therapy, Laboratory of Molecular Surgery, Kurume, Japan.
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Marcha JA, Boulaiz H, Peran M, Prados JC, Campos J, Gonzalez FJ, Rodriguez-Serrano F, Melguizo C, Velez C, Carrillo E, Hita F, Ortiz R, Martinez-Amat A, Caba O, Ventura C, Aranega A, 2009, Cancer stem cells and differentiation therapy. In: Macrcha JA et al, ed, Therapeutic potential of differentiation in cancer and normal stem cells, 1st edn. Nova Science Publishers Inc, New York
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 525
EP 533
DI 10.1007/s12253-010-9342-y
PG 9
ER
PT J
AU Jankovic Velickovic, L
Dolicanin, Z
Hattori, T
Pesic, I
Djordjevic, B
Stojanovic, M
Stankovic, J
Visnic, M
Stefanovic, V
AF Jankovic Velickovic, Ljubinka
Dolicanin, Zana
Hattori, Takanori
Pesic, Ivana
Djordjevic, Biljana
Stojanovic, Mariola
Stankovic, Jablan
Visnic, Milan
Stefanovic, Vladisav
TI Divergent Squamous Differentiation in Upper Urothelial Carcinoma—Comparative Clinicopathological and Molecular Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Divergent differentiation; Squamous metaplasia; Molecular markers; Proliferative activity; Upper urothelial carcinoma
ID Divergent differentiation; Squamous metaplasia; Molecular markers; Proliferative activity; Upper urothelial carcinoma
AB Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p<0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p<0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p=0.007), Ki-67 activity (p=0.016) and growth (p=0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.
C1 [Jankovic Velickovic, Ljubinka] Faculty of Medicine, Institute of PathologyNis, Serbia.
[Dolicanin, Zana] Faculty of Medicine, Institute of PathologyNis, Serbia.
[Hattori, Takanori] Shiga University of Medical Science, Department of PathologyOhtsu, Japan.
[Pesic, Ivana] Faculty of Medicine, Institute of PathophysiologyNis, Serbia.
[Djordjevic, Biljana] Faculty of Medicine, Institute of PathologyNis, Serbia.
[Stojanovic, Mariola] Public Health Institute, Department of StatisticsNis, Serbia.
[Stankovic, Jablan] Faculty of Medicine, Clinic of SurgeryNis, Serbia.
[Visnic, Milan] Faculty of Medicine, Clinic of SurgeryNis, Serbia.
[Stefanovic, Vladisav] Faculty of Medicine, Institute of Nephrology, Bul. Zorana Djindjica 81, 18000 Nis, Serbia.
RP Stefanovic, V (reprint author), Faculty of Medicine, Institute of Nephrology, 18000 Nis, Serbia.
EM stefan@ni.ac.rs
CR Shanks JH, Iczkowski KA, 2009, Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics. Histopathology 54:885–900
Nigwekar P, Amin BM, 2008, The many faces of urothelial carcinoma. An update with an emphasis on recently described variants. Adv Anat Pathol 15:218–233
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Martin EJ, Jenkins JB, Zuk JR, Blandy PJ, Baithun IS, 1989, Clinical importance of squamous metaplasia in invasive transitional cell carcinoma of the bladder. J Clin Pathol 42:250–253
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Lopez-Beltran A, Sauter G, Gasser T, Hartmann A, Schmitz- Drager BJ, Helpap B, Ayala AG, Tamboli P, Knowles MA, Sidransky D, Cordon-Cardo C, Jones PA, Cairns P, Simon R, Amin MB, Tyezinski JE, 2004, Tumors of the urinary system. Infiltrating urothelial carcinoma. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA, eds, World Health Organization classification of tumours. Pathology and genetics. Tumours of the urinary system and male genital organs. IARC, Lyon, pp 93–109
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Xue-Ru Wu, 2005, Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 5:713–725
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 535
EP 539
DI 10.1007/s12253-010-9343-x
PG 5
ER
PT J
AU Horvath, Zs
Torday, L
Hitre, E
Ganofszky, E
Juhos,
Czegledi, F
Urban, L
Polgar, Cs
Lang, I
Eckhardt, S
Kasler, M
AF Horvath, Zsolt
Torday, Laszlo
Hitre, Erika
Ganofszky, Erna
Juhos, Eva
Czegledi, Ferenc
Urban, Laszlo
Polgar, Csaba
Lang, Istvan
Eckhardt, Sandor
Kasler, Miklos
TI Inflammatory Breast Cancer—Comparing the Effectivity of Preoperative Docetaxel-Epirubicine Protocol to Conventional Antracycline-Containing Chemotherapy to Achieve Clinical Benefit and Complete Pathological Response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anthracycline; Docetaxel; Inflammatory breast cancer; Pathological complete remission; Primary systemic chemotherapy
ID Anthracycline; Docetaxel; Inflammatory breast cancer; Pathological complete remission; Primary systemic chemotherapy
AB Our retrospective analysis compared the effectiveness of conventional antracycline-containing protocols (A+) and docetaxel/epirubicine (TE) as primary systemic chemotherapies (PSCT) for inflammatory breast cancer (IBC). Seventy IBC patients received either A+(n=48) or TE (n=22) as PSCT. The objective clinical response and clinical benefit rate of treated patients were 54.3% (A+: 54,2% vs. TE: 54,5%; p=0,28) and 92.8% (A+: 91,7% vs. TE: 95,5%; p=0,57), respectively. The clinical complete response rate (cCR) was 23.2% (A+: 27,1% vs. TE:4,5%; χ2=4,79; p=0,03) with 7.14% (A+: 10,4% vs. TE:0%; χ2=2,47; p=0,12) of pathological complete responses (pCR). The median progression free (PFS)/local progression free (LPFS)/overall survival (OS) was 2.0/5.4/4.0 years, respectively. Patients achieving cCR had a tendency for better survival parameters than patients with less than cCR. Response rates or survival data were not statistically different in the two chemotherapy (CT) treatment groups. The survival was not influenced by the number of CT cycles in either protocols. In this set of patients, the clinical efficacy of the two alternative primary systemic chemotherapies (A+and TE) is equivalent in the treatment of inflammatory breast cancer (IBC), despite of the significant difference in favour of A+noticed in CRs. Six cycles of CT could be enough for patients achieving CR, however sequential pre- and/or postoperative CT with non crossresistant drugs should be considered for non-responders.
C1 [Horvath, Zsolt] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Torday, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H6720 Szeged, Hungary.
[Hitre, Erika] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Ganofszky, Erna] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Juhos, Eva] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Czegledi, Ferenc] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Urban, Laszlo] Petz Aladar County et University Teaching Hospital, Oncopulmonolgic Centre, Vasvary u. 2-4, H9024 Gyor, Hungary.
[Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Lang, Istvan] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Eckhardt, Sandor] National Institute of Oncology, Department of Diagnostic Pathology, Rath Gy u 7-9, H1122 Budapest, Hungary.
[Kasler, Miklos] National Institute of Oncology, Department of Diagnostic Pathology, Rath Gy u 7-9, H1122 Budapest, Hungary.
RP Horvath, Zs (reprint author), National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, H1122 Budapest, Hungary.
EM hor.zsolt@oncol.hu;zsodicsom@gmail.com
CR Levine PH, Steinhorn SC, Ries LG, Aron JL, 1985, Inflammatory breast cancer: the experience of the surveillance, epidemiology, and end results, SEER, program. J Natl Cancer Inst 74:291–297
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Low JA, Berman AW, Steinberg SM et al, 2004, Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. J Clin Oncol 22:4067–4074
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Kuerer HM, Newman LA, Smith TL et al, 1999, Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 541
EP 550
DI 10.1007/s12253-010-9344-9
PG 10
ER
PT J
AU Vereczkey, I
Serester, O
Dobos, J
Gallai, M
Szakacs, O
Szentirmay, Z
Toth, E
AF Vereczkey, Ildiko
Serester, Orsolya
Dobos, Judit
Gallai, Monika
Szakacs, Orsolya
Szentirmay, Zoltan
Toth, Erika
TI Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Borderline; Molecular; Mucinous; Ovary; Pathogenesis; Serous
ID Borderline; Molecular; Mucinous; Ovary; Pathogenesis; Serous
AB The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.
C1 [Vereczkey, Ildiko] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Serester, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Dobos, Judit] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Gallai, Monika] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Szakacs, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Szentirmay, Zoltan] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gy u 7-9, 1122 Budapest, Hungary.
RP Vereczkey, I (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, 1122 Budapest, Hungary.
EM vereczkey.ildiko@oncol.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 551
EP 559
DI 10.1007/s12253-010-9345-8
PG 9
ER
PT J
AU Li, QL
Yang, ZL
Liu, JQ
Miao, XY
AF Li, Qing-Long
Yang, Zhu-Lin
Liu, Jie-Qiong
Miao, Xiong-Ying
TI Expression of CDX2 and Hepatocyte Antigen in Benign and Malignant Lesions of Gallbladder and Its Correlation with Histopathologic Type and Clinical Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder cancer; Chronic cholecystitis; CDX2; Hepatocyte antigen (Hep); Hepatocyte paraffin 1; Immunohistochemistry; Clinicopathology
ID Gallbladder cancer; Chronic cholecystitis; CDX2; Hepatocyte antigen (Hep); Hepatocyte paraffin 1; Immunohistochemistry; Clinicopathology
AB Recent studies have shown that both CDX2 and Hepatocyte antigen (Hep) are detected in different types of cancer and associated with clinical prognosis. However, fever studies have examined gallbladder cancer specimens, and little is known about the clinicopathological significance of both CDX2 and Hep expression in gallbladder adenocarcinomas. In present study, we examined the expression frequencies of CDX2 and Hepatocyte antigen (Hep), and explored their clinicopathologic significances in gallbladder adenocarcinoma. Immunohistochemistry was used to detect and compare the frequencies of CDX2 and Hep expression in 108 samples of gallbladder adenocarcinoma, 46 peri-tumor tissues and 35 chronic cholecystitis. The expression frequencies for CDX2 and Hep were 49/108 (45.4%) and 45/108 (41.7%) in gallbladder carcinoma; 13/46 (28.3%) and 11/46 (23.9) in peri-tumor tissues; 5/35 (14.3%) and 2/35 (5.7%) in chronic cholecystitis. The positive staining of CDX2 or Hep in gallbladder adenocarcinoma was significantly higher than that in peritumoral tissues (both, P<0.05), and chronic cholecystits (both, P<0.01). The expression of CDX2 or Hep was negatively correlated to grade of differentiation, tumor size and lymph node metastasis (P<0.01 or P<0.05). Elevated expression frequency of CDX2 or Hep was associated with increased overall survival (P=0.003 or P=0.002). Multivariate Cox regression analysis showed that CDX2 (P=0.014) or Hep (P=0.026) expression was an independent prognostic predictor in gallbladder adenocarcinoma. CDX2 and Hep might function as important biological markers in the development and prognosis of gallbladder adenocarcinoma.
C1 [Li, Qing-Long] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 139 Middle Renmin Road, 410011 Changsha, Hunan, China.
[Yang, Zhu-Lin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 139 Middle Renmin Road, 410011 Changsha, Hunan, China.
[Liu, Jie-Qiong] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 139 Middle Renmin Road, 410011 Changsha, Hunan, China.
[Miao, Xiong-Ying] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 139 Middle Renmin Road, 410011 Changsha, Hunan, China.
RP Yang, ZL (reprint author), Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, China.
EM zhulin.yang@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 561
EP 568
DI 10.1007/s12253-010-9346-7
PG 8
ER
PT J
AU Iyengar, B
Singh, VA
AF Iyengar, Bhanu
Singh, V Avantika
TI Embryonic Vasculogenesis in Nodular Melanomas and Tumour Differentiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Vasculogenic mimicry; Incorporated microvasculature; Pigmented .Amelanotic; Laminin; Integrin
ID Vasculogenic mimicry; Incorporated microvasculature; Pigmented .Amelanotic; Laminin; Integrin
AB The relationship of vasculogenic mimicry to pigment in nodular vertical growth phase [VGP] cutaneous melanomas is assessed in this study. 10 nodules each from 27 tumors, 15 pigmented and 12 amelanotic were sampled in proportion to the pigment level. Serial frozen and paraffin sections subjected to HE, Reticulin, PAS to assess the vascular pattern; Dopa Oxidase and Immunopositivity for HMB45, LN5 [laminin 5] & integrin[α5β1], and EM [electron microscopy] to identify Weibel-Palade bodies within endothelial cells. The vascular pattern, pigment and the immunopositivity was mapped to assess the percentage VM [vasculogenic sinusoids] vs INC [incorporated microvasculature]. In pigmented melanomas, INC from preexisting stromal vessels is predominant. Amelanotic melanomas show embryonic vasculogenic mimicry, a selfpropagating system of spaces within the sheets of tumors cells. Both INC and VM co-exist in tumors with both amelanotic and melanotic nodules. In areas with VM, loci of LN5 and α5β1 integrin positive cells appear within the proliferating columns, positivity in these cells suggesting a switch to a more aggressive form. Irregular spaces appear lined by tumor cells, with initial hemopoeitic activity, coalesce and interlink into tubular networks. Spaces lined by tumor cells extend into an intricate network which then connects with the angiogenetic system. The tumor cells lining the vasculogenic spaces are positive for LN5, α5β1 integrin. Statistically, INC is significantly higher in pigmented melanomas, whereas amelanotic melanomas show significantly higher VM. Pigmentation is correlated positively with INC and negatively with VM. INC and VM are negatively correlated with each other.
C1 [Iyengar, Bhanu] Iyengar Farm, Pigment Cell Center, Brijwasan Road, PO Kapashera, 110037 New Delhi, India.
[Singh, V Avantika] Iyengar Farm, Pigment Cell Center, Brijwasan Road, PO Kapashera, 110037 New Delhi, India.
RP Iyengar, B (reprint author), Iyengar Farm, Pigment Cell Center, 110037 New Delhi, India.
EM bhanu_i@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 569
EP 577
DI 10.1007/s12253-010-9350-y
PG 9
ER
PT J
AU Mehdi, JS
Ali, A
Rizvi, AM
AF Mehdi, Jafar Syed
Ali, Asgar
Rizvi, Alam Moshahid
TI Parkin Gene Alterations in Ovarian Carcinoma from Northern Indian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Loss of heterozygosity; Ovarian cancer; Parkin gene; Reverse transcriptase PCR; Tumor suppressor gene
ID Loss of heterozygosity; Ovarian cancer; Parkin gene; Reverse transcriptase PCR; Tumor suppressor gene
AB Parkin, a tumor suppressor gene located on chromosome 6q25-27, has been identified as a target for mutation in many human malignancies like breast, ovaries, cervical and lungs etc. After a preliminary report on the loss of heterozygosity and altered Parkin expression in breast and ovarian tumors, we aimed to study loss of heterozygosity in the Parkin gene associated microsatellite markers and its expression in human ovarian cancer patients from Indian population. We examined 102 paired normal and ovarian cancer samples for allelic loss in Parkin gene locus using Parkin gene associated microsatellite markers through loss of heterozygosity and changes in its expression through semiquantitative RT-PCR. Loss of heterozygosity identified common region of loss in Parkin locus with highest frequency for the intragenic marker D6S1599 (53%) whereas, 49 of 102 (48%) specimens showed decreased or no expression of Parkin in ovarian tumors. The study revealed that presence of loss of heterozygosity was significantly higher in both the intragenic markers (D6S1599 and D6S305) as compared with the locus of flanking region (D6S1008) with their p value 0.000001 and 0.00008, respectively. It also revealed that Parkin inactivation is probably a combination of loss of heterozygosity coupled with downregulation of Parkin gene through an alternative means like epigenetic mechanism. These data strongly supports the previous study and argue that Parkin is a tumor suppressor gene whose inactivation may play an important role in ovarian carcinoma.
C1 [Mehdi, Jafar Syed] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar MargNew Delhi, India.
[Ali, Asgar] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar MargNew Delhi, India.
[Rizvi, Alam Moshahid] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar MargNew Delhi, India.
RP Rizvi, AM (reprint author), Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, New Delhi, India.
EM rizvijmi@gmail.com
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Preacher KJ, 2001, Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence [Computer software]. Available from http:// www.quantpsy.org
Foulkes WD, Ragoussis J, Stamp GWH, Allan GJ, Trowsdale J, 1993, Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma. Br J Cancer 67:551–559
WanMZT, D’Abling G, Zheng I, VeliscuM, Dubeau L, 1994, Three distinct regions of chromosome 6 are targets of loss of heterozygosity in human ovarian carcinomas. J Oncol 5:1043–1048
Agirre X, Roman-Gomez J, Vazquez I, Jimenez-Velasco A, Garate L, Montiel-Duarte C, Artieda P, Cordeu L, Lahortiga I, Calasanz MJ, Heiniger A, Torres A, Minna JD, Prosper F, 2006, Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia. Int J Cancer 118:1945–1953
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 579
EP 586
DI 10.1007/s12253-010-9351-x
PG 8
ER
PT J
AU Cui, Q
Jiang, W
Guo, J
Liu, Ch
Li, D
Wang, X
Zeng, Y
AF Cui, Qiu
Jiang, Weihao
Guo, Jun
Liu, Cheng
Li, Dingfeng
Wang, Xiaohong
Zeng, Yanjun
TI Relationship Between Hypermethylated MGMT Gene and Osteosarcoma Necrosis Rate After Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; DNA methylation; CpG island; Drug resistance; Neoplasm; O6-Methylguanine-DNA Methyltransferase
ID Osteosarcoma; DNA methylation; CpG island; Drug resistance; Neoplasm; O6-Methylguanine-DNA Methyltransferase
AB To investigate the relativity of MGMT(O-6-methylguanine-DNA methyltransferase) gene methylation from patients with protein expression and osteosarcoma necrosis rate after chemotherapy. Fifty-one oteosarcoma tissues were collected, Methylation of MGMT gene promoter was detected by methylation-specific PCR method, and protein expression of MGMT was examined by immunohistochemistry procedure, the relationship between methylated MGMT gene expression and patients response to chemotherapy was analyzed. The positive ratio of methylation MGMT gene promoter in 51 patients was 23.5% (12 in 51). Negative percentage of protein expression of MGMT was 27.5% (14 in 51). It seemed that methylation of MGMT gene in osteosarcoma tissues had no evident relationship with the patient’s age, sexuality, and the size and type of neoplasms, etc. The necrosis rates of methylated MGMT of osteosarcoma (tumor grade from I to IV) were 0 (0/51), 3.9% (2/51), 5.9% (3/51), 13.7% (7/51), respectively. In contrast, the necrosis rates of unmethylated MGMT of osteosarcoma (tumor grade from I to IV) were 45.1% (23/51), 25.5% (13/51), 3.9% (2/51), 2.0% (1/51), respectively. It suggest that methylated and unmethylated MGMT gene of osteosarcoma have significant difference in protein expression. The unmethylated MGMT gene has higher positive protein expression (u=−4.92, P<0.001). Methylation of MGMT gene has higher tumor necrosis rate in osteosarcoma patients. Methylation in MGMT promoter may be important for judging the effect of chemotherapy in Osteosarcoma patients.
C1 [Cui, Qiu] 307 Hospital of PLA, Department of Orthopedics, PLA 307th Hospital, 100071 Beijing, China.
[Jiang, Weihao] 307 Hospital of PLA, Department of Orthopedics, PLA 307th Hospital, 100071 Beijing, China.
[Guo, Jun] 307 Hospital of PLA, Department of Orthopedics, PLA 307th Hospital, 100071 Beijing, China.
[Liu, Cheng] 307 Hospital of PLA, Department of Orthopedics, PLA 307th Hospital, 100071 Beijing, China.
[Li, Dingfeng] 307 Hospital of PLA, Department of Orthopedics, PLA 307th Hospital, 100071 Beijing, China.
[Wang, Xiaohong] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
[Zeng, Yanjun] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
RP Li, D (reprint author), 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
EM 307yygk@sina.com
CR Sabharwal A, Middleton MR, 2006, Exploiting the role of O6- methylguanine DNA Methyltransferase, MGMT, in cancer therapy[J]. Curr Opin Pharmacol 6(4):355–363
Kaina B, ChristmannM, Naumann S, Roos WP, 2007, MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents[J]. DNA Repair, Amst, 6(8):1079–99
Jacinto FV, Esteller M, 2007, MGMT hypermethylation: a prognostic foe, a predictive friend[J]. DNA Rep 10(1):10–16
Helleday T, Petermann E, Lundin C et al, 2008, DNA repair pathways as targets for cancer therapy[J]. Nat Rev 8(3):193–204
Rosen G, Caparros B, Huvos AG et al, 1982, Preoperative chemotherapy for osteogenic sarcoma: selection of Postoperativeadjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy [J]. Cancer 49(6):1221–1230
Lee S, Kim WH, Jung HY et al, 2002, Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma [J]. Am J Pathol 161(3):1015–1022
Ho JW, 2006, Potential and cytotoxicity of cis-Platinum complex with anti-tumor activity in combination therapy[J]. Recent Patents on Anti-Cancer Drug Discovery 1:129–134
Sabharwal A, Middleton MR, 2006, Exploiting the role of O6- methylguanine DNA methyltransferase, MGMT, in cancer therapy[ J]. Curr Opin Pharmascol 6(4):355–363
Verbeek B, Southgate TD, Gilham DE, Margison GP, 2008, O6- Methylguanine-DNA methyltransferase inactivation and chemotherapy[ J]. Br Med Bull 85:17–33
Voelter V, Diserens AC, Moulin A et al, 2008, Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma[J]. Int J Cancer 123(5):1215–8
Gal-Yan EN, Saito Y, Egger G et al, 2008, Cancer epigenetics: modifications, screening, and therapy[J]. Annu Rev Med 59:267– 280
Weisenberger DJ, Siegmund KD, Campan M et al, 2006, CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38:787–793
Kawaguchi K, Oda Y, Saito T et al, 2006, DNA hypermethylation status of multiple genes in soft tissue sarcomas[J]. Mod Pathol 19, 1):106–114
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 587
EP 591
DI 10.1007/s12253-010-9354-7
PG 5
ER
PT J
AU Beketic-Oreskovic, L
Ozretic, P
Rabbani, NZ
Jackson, LI
Sarcevic, B
Levanat, S
Maric, P
Babic, I
Vujaskovic, Z
AF Beketic-Oreskovic, Lidija
Ozretic, Petar
Rabbani, N Zahid
Jackson, L Isabel
Sarcevic, Bozena
Levanat, Sonja
Maric, Petra
Babic, Ivan
Vujaskovic, Zeljko
TI Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 8-OHdG; Breast cancer; CA-IX; CD105; Survival analysis
ID 8-OHdG; Breast cancer; CA-IX; CD105; Survival analysis
AB The aimof this studywas to examine the prognostic significance of carbonic anhydrase IX (CA-IX), an endogenous marker for tumor hypoxia; endoglin (CD105), a proliferation-associated and hypoxia-inducible glycoprotein and 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative DNA lesion, in breast cancer patients. Immunohistochemical expressions of CA-IX, CD105 and 8-OHdG, analyzed on paraffin-embedded tumor tissues from forty female breast cancer patients, were used to assess their prognostic implication on overall survival (OS) and relapse-free survival (RFS). Patients with high CA-IX expression (above cut-off value) had a higher occurrence of relapse (P=0.002). High CA-IX expression was significantly associated with shorter RFS (P<0.001, hazard ratio (HR) 0.21) and shorter OS (P<0.001, HR 0.19). Lymph node negative patients with high CA-IX expression had worse RFS (P=0.031, HR 0.14) and OS (P=0.005, HR 0.05). Patients with grade I&II tumors and high CA-IX expression showed shorter RFS (P=0.028, HR 0.28) and OS (P=0.008, HR 0.20). Worse OS (P=0.046, HR 0.28) was found in subgroup of patients with grade II tumors and high CA-IX expression. Among all three markers, only high CA-IX expression was strong independent prognostic indicator for shorter OS (HR 4.14, 95% CI 1.28–13.35, P=0.018) and shorter RFS (HR 3.99, 95% CI 1.38–11.59, P=0.011). Elevated expression of CA-IX was an independent prognostic factor for decreased RFS and OS and a significant marker for tumor aggressiveness. CD105 had week prognostic value; whereas, 8-OHdG, in this study, did not provide sufficient evidence as a prognostic indicator in breast cancer patients.
C1 [Beketic-Oreskovic, Lidija] University Hospital for Tumors, University of Zagreb, School of Medicine, Department of Radiation Oncology, Ilica 197, 10000 Zagreb, Croatia.
[Ozretic, Petar] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
[Rabbani, N Zahid] Duke University Medical Center, Department of Radiation OncologyDurham, NC, USA.
[Jackson, L Isabel] Duke University Medical Center, Department of Radiation OncologyDurham, NC, USA.
[Sarcevic, Bozena] University Hospital for Tumors, University of Zagreb, School of Medicine, Department of PathologyZagreb, Croatia.
[Levanat, Sonja] Rudjer Boskovic Institute, Department of Molecular MedicineZagreb, Croatia.
[Maric, Petra] University Hospital for Tumors, University of Zagreb, School of Medicine, Department of Radiation Oncology, Ilica 197, 10000 Zagreb, Croatia.
[Babic, Ivan] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and GynecologyZagreb, Croatia.
[Vujaskovic, Zeljko] Duke University Medical Center, Department of Radiation OncologyDurham, NC, USA.
RP Maric, P (reprint author), University Hospital for Tumors, University of Zagreb, School of Medicine, Department of Radiation Oncology, 10000 Zagreb, Croatia.
EM lidija.beketic.oreskovic@zg.t-com.hr
CR Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics. CA Cancer J Clin 58:71–96
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 593
EP 603
DI 10.1007/s12253-010-9355-6
PG 11
ER
PT J
AU Matsumoto, N
Umezawa, T
Sasaki, T
Nakajima, K
Kanetsuna, Y
Sasaki, H
AF Matsumoto, Naoki
Umezawa, Takashi
Sasaki, Toru
Nakajima, Kuninobu
Kanetsuna, Yukiko
Sasaki, Hiroshi
TI Clinical and Prognostic Value of the Presence of Irregular Giant Nuclear Cells in pT1 Ovarian Clear Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intraoperative diagnosis; Nuclear morphometry; Ovarian cancer; Pathology; Touch imprint cytology
ID Intraoperative diagnosis; Nuclear morphometry; Ovarian cancer; Pathology; Touch imprint cytology
AB In the early stages of epithelial ovarian cancer, histopathological grading is important. However, the grading of ovarian clear cell carcinoma (OCCC) remains controversial. We aimed to identify irregular giant nuclear cells (IGNCs) by a simple method in clinical practice, and to evaluate the prognostic value of IGNCs in pT1 OCCC. Eighty-seven pT1 OCCC patients who underwent initial surgery at Jikei University Kashiwa Hospital, Chiba, Japan, were retrospectively assessed. Paraffin-embedded tissue sections (PTSs) stained with hematoxylin and eosin were reviewed. Giant nuclear cells (GNCs) were defined as cells with a nuclear length of more than twice the median nuclear length. GNCs with irregular nuclear circumferences were defined as IGNCs. Cases where one or more GNCs existed and where IGNCs accounted for >10% of the GNCs were classified as IGNC-positive. We also attempted to identify IGNCs on touch imprint cytology smears (TICSs). Among the 87 cases, 68 were IGNC-negative and 19 were IGNC-positive. The 5-year disease-free and overall survival rates were 88.9% and 90.3% in the total patients, 98.3% and 100% in the IGNC-negative group, and 59.7% and 62.0% in the IGNC-positive group, respectively. These survival rates were significantly lower in the IGNC-positive group than in the IGNC-negative group (adjusted hazard ratio=14, 95% confidence interval=2.7–124 and adjusted hazard ratio=25, 95% confidence interval=2.9–768, respectively). Prognostic differences were not identified for other factors. IGNC identification on 28 available TICSs predicted IGNC identification on PTSs (sensitivity=50.0%, specificity=100%, P=0.007). The presence of IGNCs has clinical and prognostic value for pT1 OCCC.
C1 [Matsumoto, Naoki] Jikei University Kashiwa Hospital, Department of Obstetrics and Gynecology, 163-1 Kashiwashita, 277-8567 Kashiwa, Chiba, Japan.
[Umezawa, Takashi] Jikei University School of Medicine, Department of PathologyTokyo, Japan.
[Sasaki, Toru] Tokyo Medical University, Department of Obstetrics and GynecologyTokyo, Japan.
[Nakajima, Kuninobu] Jikei University School of Medicine, Department of Obstetrics and GynecologyTokyo, Japan.
[Kanetsuna, Yukiko] Jikei University Kashiwa Hospital, Department of Clinical PathologyKashiwa, Chiba, Japan.
[Sasaki, Hiroshi] Jikei University Kashiwa Hospital, Department of Obstetrics and Gynecology, 163-1 Kashiwashita, 277-8567 Kashiwa, Chiba, Japan.
RP Matsumoto, N (reprint author), Jikei University Kashiwa Hospital, Department of Obstetrics and Gynecology, 277-8567 Kashiwa, Japan.
EM nmazmoto@my.home.ne.jp
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Rioux-Leclercq N, Karakiewicz PI, Trinh QD et al, 2007, Prognostic ability of simplified nuclear grading of renal cell carcinoma. Cancer 109:868–874
Novara G, Martignoni G, Artibani Wet al, 2007, Grading systems in renal cell carcinoma. J Urol 177:430–436
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 605
EP 611
DI 10.1007/s12253-010-9356-5
PG 7
ER
PT J
AU Chen, CHA
Waterboer, T
Keleher, A
Morrison, B
Jindal, Sh
McMillan, D
Nicol, D
Gardiner, AR
McMillan, AJN
Antonsson, A
AF Chen, C-H Alice
Waterboer, Tim
Keleher, Annie
Morrison, Beth
Jindal, Shalini
McMillan, Denise
Nicol, David
Gardiner, A Robert
McMillan, A J Nigel
Antonsson, Annika
TI Human Papillomavirus in Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Benign prostatic hyperplasia (BPH); Human papillomavirus (HPV); Polymerase chain reaction (PCR); Prostate cancer; Serology
ID Benign prostatic hyperplasia (BPH); Human papillomavirus (HPV); Polymerase chain reaction (PCR); Prostate cancer; Serology
AB The aim of this study was to determine the prevalence of human papillomavirus (HPV) types in tissue and HPV antibodies in prostatic disease. Prostate tissue samples were collected from 51 patients diagnosed with adenocarcinoma and 11 with benign prostatic hyperplasia (BPH). All tissue samples were confirmed by histology. Plasma samples were available for 52 prostate patients. We investigated HPV DNA prevalence by PCR, and PCR positive samples were HPV type determined by sequencing. Prevalence of antibodies against twenty-seven HPV proteins from fourteen different HPV types was assessed in the plasma samples. The HPV DNA prevalence in the tissue samples was 14% (7/51) for prostate cancer samples and 27% (3/11) for BPHs. HPV-18 was the only type detected in tissue samples (10/62). No significant difference in HPV prevalence between the prostate cancer and BPH samples was found. HPV-positive cells were identified in eight of our thirteen prostate tissue slides (3/3 BPH and 5/10 adenocarcinoma) by in situ hybridisation, and the positive cells were found in epithelial cells and peripheral blood cells. Serology data showed no significant increase in levels of antibodies against any of the HPV-18 proteins tested for in prostatic disease patients. Antibodies against HPV-1, HPV-4, HPV-6 and HPV-11 were significantly higher in the group of males with prostatic disease. Our study did not show an association between prostatic disease and either presence of HPV DNA in samples or previous exposure of high-risk HPV.
C1 [Chen, C-H Alice] The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, QLD, Australia.
[Waterboer, Tim] German Cancer Research Center (DKFZ), Infection and Cancer Program, 69120 Heidelberg, Germany.
[Keleher, Annie] The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, QLD, Australia.
[Morrison, Beth] The University of Queensland, Princess Alexandra Hospital, Department of Urology, Central Clinical Division, 4102 Brisbane, QLD, Australia.
[Jindal, Shalini] Dame Roma Mitchell Cancer Research Laboratories, 5000 Adelaide, SA, Australia.
[McMillan, Denise] The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, QLD, Australia.
[Nicol, David] The University of Queensland, Princess Alexandra Hospital, Department of Urology, Central Clinical Division, 4102 Brisbane, QLD, Australia.
[Gardiner, A Robert] The University of Queensland, Royal Brisbane Hospital, Department of Surgery, Central Clinical Division, 4029 Brisbane, QLD, Australia.
[McMillan, A J Nigel] The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, QLD, Australia.
[Antonsson, Annika] The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, QLD, Australia.
RP Antonsson, A (reprint author), The University of Queensland, Princess Alexandra Hospital, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, 4102 Brisbane, Australia.
EM annika.antonsson@qimr.edu.au
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 613
EP 617
DI 10.1007/s12253-010-9357-4
PG 5
ER
PT J
AU Vural,
Uluoglu,
Akyurek, N
Oguz, A
Karadeniz, C
AF Vural, Cigdem
Uluoglu, Omer
Akyurek, Nalan
Oguz, Aynur
Karadeniz, Ceyda
TI The Evaluation of CD99 Immunoreactivity and EWS/FLI1 Translocation by Fluorescence in situ Hybridization in Central PNETs and Ewing’s Sarcoma Family of Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ewing’s sarcoma family of tumors; Peripheral primitive neuroectodermal tumor; CD99; EWS-FLI1 translocation; Fluorescence in situ hybridization
ID Ewing’s sarcoma family of tumors; Peripheral primitive neuroectodermal tumor; CD99; EWS-FLI1 translocation; Fluorescence in situ hybridization
AB Ewing’s sarcoma family of tumors (ESFTs) are indicated by malignant, small, round and blue cell tumors of the bone and soft tissue. Gene rearrangements between EWS gene on chromosome 22q12 and members of the ETS gene family are common in and specific to ESFTs. Another defining characteristic of ESFTs is their membranous expression of the CD99. In contrast, such translocations and immunoreactivity are not found in central primitive neuroectodermal tumors (cPNETs). The aim of this study was to investigate the detection of EWS/FLI1 translocations and CD99 immunoreactivity in order to evaluate their clinicopathological features and their roles in the differential diagnosis of these tumors. In this study, we investigated CD99 immunoreactivity using immunohistochemistry and Ewing’s sarcoma / Friend leukaemia virus integration 1 (EWS/FLI1) translocation using the fluorescence in situ hybridization (FISH) method in 23 cases. CD99 expression was detected in 10/11 (90%) ESFT cases and 2/7 cPNET cases. In 18 cases EWS/FLI1 translocation was examined using the FISH method. The EWS/FLI1 translocations were detected in 7/8 (87.5%) ESFTs cases, whereas non of 8 cPNET cases were detected with this translocation. One case could not be classified as either central or peripheral, showed EWS/FLI1 translocation. There was a statistically significant difference in CD99 expression (p=0.0013) and EWS/FLI1 translocation (p=0,002) between cPNETs and ESFTs cases. In conclusion, CD99 expression and EWS/FLI1 translocation are specific and sensitive markers in the diagnosis of ESFTs. However, these were often not found in cases of cPNET. Therefore, in the diagnosis of ESFTs, clinical, radiological, histopathological and immunohistochemical parameters should always be evaluated together.
C1 [Vural, Cigdem] Baskent University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Uluoglu, Omer] Gazi University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Akyurek, Nalan] Gazi University Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Oguz, Aynur] Gazi University Faculty of Medicine, Department of Pediatric OncologyAnkara, Turkey.
[Karadeniz, Ceyda] Gazi University Faculty of Medicine, Department of Pediatric OncologyAnkara, Turkey.
RP Vural, (reprint author), Baskent University Faculty of Medicine, Department of Pathology, Ankara, Turkey.
EM dr.cvural@gmail.com
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Llombart-Bosch A, Navarro S, 2001, Immunohistochemical detection of EWS and FLI-1 proteins in ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99, MIC-2, expression. Appl Immunohistochem Mol Morphol 9(3):255–260
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Mhawech-Fauceglia P, Hermann F, Penetrante R et al, 2006, Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, break-apart probe fluorescence in situ, FISH, analysis in ewing’s sarcoma/primitive neuroectodermal tumour, EWS/PNET): a comparative study with CD99 and FLI-1 polyclonal antibodies. Histopathology 49(6):569–575
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Ishii N, Hiraga H, Sawamura Y et al, 2001, Alternative EWSFLI1 fusion gene and MIC2 expression in peripheral and central primitive neuroectodermal tumors. Neuropathology 21(1):40–44
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Qian X, Jin L, Shearer BM et al, 2005, Molecular diagnosis of ewing’s sarcoma/primitive neuroectodermal tumor in formalinfixed paraffin-embedded tissues by RT-PCR and fluorescence in situ hybridization. Diagn Mol Pathol 14(1):23–28
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 619
EP 625
DI 10.1007/s12253-010-9358-3
PG 7
ER
PT J
AU Lu, L
Zhao, G
Luu-The, V
Ouellet, J
Fan, Z
Labrie, F
Pelletier, G
AF Lu, Lu
Zhao, Gang
Luu-The, Van
Ouellet, Johanne
Fan, Zhinmin
Labrie, Fernand
Pelletier, Georges
TI Expression of 11β-hydroxysteroid Dehydrogenase Type 1 in Breast Cancer and Adjacent Non-Malignant Tissue. An Immunocytochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 11β-hydroxysteroid dehydrogenase type 1; Breast cancer; Glucocorticoid receptors; Immunocytochemistry; Cortisol
ID 11β-hydroxysteroid dehydrogenase type 1; Breast cancer; Glucocorticoid receptors; Immunocytochemistry; Cortisol
AB Intratumoral biosynthesis of hormone steroids is thought to play a role in the pathogenesis and development of human breast cancer. There is evidence that glucocorticoids may inhibit the development and progression of breast cancer. 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 is the enzyme which converts inactive cortisone to active cortisol. In order to study the expression of 11β-HSD type 1 in breast cancer and non-cancerous breast tissue, we have developed specific antibodies to 11β-HSD type 1 and proceeded to localization of the enzyme in 84 specimens of breast carcinoma and adjacent nonmalignant tissues by immnohistochemistry. The results were correlated with the expression of androgen receptor, estrogen receptor, progesterone receptor, glucocorticoid receptor and CDC47, a cell division marker, as well as the tumor stage, tumor size, nodal status and menopausal status. The expression of 11β-HSD type 1 in 64% of breast cancer specimens appeared significantly lower than that observed in normal adjacent tissues (97% of cases being positive). There was no significant correlation between 11β-HSD type 1 expression and the clinicopathological parameters studied. The decrease in 11β-HSD type 1 expression in breast cancer as compared to that observed in the adjacent normal tissues may play a role in the development and/or progression of the cancer by modifying the intratumoral levels of glucocorticoids.
C1 [Lu, Lu] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
[Zhao, Gang] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
[Luu-The, Van] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
[Ouellet, Johanne] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
[Fan, Zhinmin] Jilin University, China-Japan Union Hospital, No74, Xin Min Street, 130021 Changchun, Jilin Province, China.
[Labrie, Fernand] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
[Pelletier, Georges] Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, 2705 Laurier blvd, G1V 4G2 Quebec, QC, Canada.
RP Pelletier, G (reprint author), Laval University Hospital Research Center, Molecular Endocrinology and Oncology Research Center, G1V 4G2 Quebec, Canada.
EM georges.pelletier@crchul.ulaval.ca
CR Allegra JC, Lippman ME, Thompson EB, Simon R, Barlock A, Green L, Huff KK, Do HM, Aitken SC, 1979, Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer. Cancer Res 39(5):1447–1454
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Song D, Liu G, Luu-The V, Zhao D, Want I, Zhang H, Xueling G, Li S, Desy L, Labrie F, Pelletier G, 2006, Expression of aromatase and 17β-hydroxysteroid dehydrogease types 1, 7 and 12 in breast cancer. An immunocytochemical study. J Steroid Biochem Mol Biol 101:136–144
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Wang H, Want Y, Rayburn ER, Hill DL, Rinehart JJ, Zhang R, 2007, Dexamethasone as a chemosensitizer for breast cancer chemotherapy: potentiaion of the antitumor activity of adriamycin, modulation of cytokine expression, and pharmacokinetics. Int J Clin Oncol 30(4):947–953
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 627
EP 632
DI 10.1007/s12253-011-9361-3
PG 6
ER
PT J
AU Stamatelli, A
Saetta, AA
Bei, Th
Kavantzas, N
Michalopoulos, VN
Patsouris, E
Aroni, K
AF Stamatelli, Angeliki
Saetta, A Angelica
Bei, Thaleia
Kavantzas, Nicolaos
Michalopoulos, V Nicolaos
Patsouris, Efstratios
Aroni, Kiriaki
TI B-Raf Mutations, Microsatellite Instability and p53 Protein Expression in Sporadic Basal Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal cell carcinoma; B-Raf; Microsatellite instability; p53; Skin
ID Basal cell carcinoma; B-Raf; Microsatellite instability; p53; Skin
AB Basal Cell Carcinoma (BCC) is the most common skin malignancy. Genes related to the Ras/Raf signalling pathway have been implicated in the pathogenesis of skin cancer. The objective of this study was to investigate the presence of B-Raf mutations in sporadic BCCs as well as its correlation with the phenotype of microsatellite instability (MSI), the clinicopathological parameters of the tumours and p53 protein expression. 83 BCC specimens were screened for B-Raf mutations, applying polymerase chain reaction, single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. MSI status was examined using mononucleotide microsatellite markers and p53 protein expression was demonstrated by immunohistochemical staining. A C to T transition at 1790 nucleotide leading to a silent mutation L597L; and a T to A transversion causing an amino acid change (F610I) have been found. MSI was detected in 5% of the cases and p53 accumulation was present in 37/83 samples studied. Although rare B-Raf alterations have been observed in BCC, none of them harboured the hot-spot mutation T1799A commonly present in melanomas and colon carcinomas. Consequently, no correlation could be determined between B-Raf alterations, MSI status, the clinicopathological features and p53 protein expression. Our results are in favour of a secondary importance for Ras signalling cascade genes in BCC pathogenesis.
C1 [Stamatelli, Angeliki] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
[Saetta, A Angelica] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
[Bei, Thaleia] NIH, National Institutes of Child Health and Human Development, 20892 Bethesda, MD, USA.
[Kavantzas, Nicolaos] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
[Michalopoulos, V Nicolaos] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
[Aroni, Kiriaki] University of Athens, Medical School, Department of Pathology, 75 Mikras Asias Str, GR-115 27 Athens, Greece.
RP Stamatelli, A (reprint author), University of Athens, Medical School, Department of Pathology, GR-115 27 Athens, Greece.
EM agstam@med.uoa.gr
CR Ionescu DN, Arida M, Jukic DM, 2006, Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation. Arch Pathol Lab Med 130:45–51
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 633
EP 637
DI 10.1007/s12253-011-9363-1
PG 5
ER
PT J
AU Deisch, J
Raisanen, J
Rakheja, D
AF Deisch, Jeremy
Raisanen, Jack
Rakheja, Dinesh
TI Immunoexpression of SALL4 in Wilms Tumors and Developing Kidney
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Kidney development; Nephrogenic rest; SALL4; Wilms tumor
ID Immunohistochemistry; Kidney development; Nephrogenic rest; SALL4; Wilms tumor
AB SALL4 is a zinc finger transcription factor that plays a role in the maintainence and pluripotency of embryonic stem cell and is important in renal development where SALL4 mutations give rise to renal malformations. Because Wilms tumor recapitulates renal embryogenesis, we hypothesized that Wilms tumor cells may also express SALL4. We performed immunohistochemistry for SALL4 on tissue microarray sections of Wilms tumors, nephrogenic rests, and fetal renal cortices. Half (26 out of 52) of the Wilms tumors showed SALL4 immunoreactivity, ranging from strong and diffuse to focal and weak. Blastemal, epithelial, and combined blastemal and epithelial patterns of immunoreactivity were identified. No cases showed stromal staining. In the fetal kidney, SALL4 expression was restricted to the blastema and primitive epithelium at 15 weeks’ gestation. SALL4 staining was not seen at later gestational ages, in non-neoplastic postnatal kidneys, or in nephrogenic rests. Our study is the first to demonstrate SALL4 immunoreactivity in Wilms tumors and in developing fetal kidney. The absence of SALL4 staining in nephrogenic rests, the presumed precursors of Wilms tumors, is intriguing and suggests that Wilms tumors have a pluripotency quality that may be lacking in nephrogenic rests.
C1 [Deisch, Jeremy] University of Texas Southwestern Medical Center, Department of Pathology MC 9073, 5323 Harry Hines Boulevard, 75390 Dallas, TX, USA.
[Raisanen, Jack] University of Texas Southwestern Medical Center, Department of Pathology MC 9073, 5323 Harry Hines Boulevard, 75390 Dallas, TX, USA.
[Rakheja, Dinesh] University of Texas Southwestern Medical Center, Department of Pathology MC 9073, 5323 Harry Hines Boulevard, 75390 Dallas, TX, USA.
RP Rakheja, D (reprint author), University of Texas Southwestern Medical Center, Department of Pathology MC 9073, 75390 Dallas, USA.
EM dinesh.rakheja@utsouthwestern.edu
CR Pode-Shakked N, Metsuyanim S, Rom-Gross E et al, 2009, Developmental tumourigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population. J Cell Mol Med 13:1792–1808
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Zhang J, TamWL, Tong GQ et al, 2006, Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 8:1114–1123
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Metsuyanim S, Harari-Steinberg O, Buzhor E et al, 2009, Expression of stem cell markers in the human fetal kidney. PLoS ONE 4:e6709
Ma Y, Singer DB, Gozman A et al, 2001, Hsal 1 is related to kidney and gonad development and is expressed in Wilms tumor. Pediatr Nephrol 16:701–709
Metsuyanim S, Pode-Shakked N, Schmidt-Ott KM et al, 2008, Accumulation of malignant renal stem cells is associated with epigenetic changes in normal renal progenitor genes. Stem Cells 26:1808–1817
Chai L, Yang J, Di C et al, 2006, Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development. J Biol Chem 281:18918–18926
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Al-Baradie R, Yamada K, St Hilaire C et al, 2002, Duane radial ray syndrome, Okihiro syndrome, maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet 71:1195–1199
Borozdin W, Boehm D, Leipoldt M et al, 2004, SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism. J Med Genet 41:e113
Borozdin W, Wright MJ, Hennekam RC et al, 2004, Novel mutations in the gene SALL4 provide further evidence for acrorenal- ocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. J Med Genet 41:e102
Kohlhase J, Chitayat D, Kotzot D et al, 2005, SALL4 mutations in Okihiro syndrome, Duane-radial ray syndrome), acro-renalocular syndrome, and related disorders. Hum Mutat 26:176–183
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Miertus J, Borozdin W, Frecer Vet al, 2006, A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet 119:154–161
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 639
EP 644
DI 10.1007/s12253-011-9364-0
PG 6
ER
PT J
AU Mise, J
Dembitz, V
Banfic, H
Visnjic, D
AF Mise, Josko
Dembitz, Vilma
Banfic, Hrvoje
Visnjic, Dora
TI Combined Inhibition of PI3K and mTOR Exerts Synergistic Antiproliferative Effect, but Diminishes Differentiative Properties of Rapamycin in Acute Myeloid Leukemia Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ATRA; Leukemia; PI3K; PMA; Rapamycin
ID ATRA; Leukemia; PI3K; PMA; Rapamycin
AB A novel strategy has been suggested to enhance rapamycin-based cancer therapy through combining mammalian target of rapamycin (mTOR)-inhibitors with an inhibitor of the phosphatydilinositol 3-kinase PI3K/Akt or mitogen-activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) pathway. However, recent study demonstrated the potentiating effect of rapamycin on all-trans-retinoic acid (ATRA)-mediated differentiation of acute myelogenous leukemia (AML) cells, prompting us to investigate the effects of longitudinal inhibition of PI3K/Akt/mTOR signaling pathway on both proliferation and differentiative capacity of AML. In NB4, HL-60, U937 and K562 cell lines, rapamycin exerted minimal antiproliferative effects, and combining PI3K inhibitor LY 294002 and rapamycin inhibited proliferation more than LY 294002 alone. Rapamycin potentiated differentiation of ATRA-treated NB4 cells, but the combination of rapamycin and LY 294002 inhibited the expression of CD11b in both ATRA- and phorbol myristate acetate (PMA)-stimulated cells more than PI3K inhibitor alone. These results demonstrate that, although the combination of PI3K inhibitor and rapamycin is more effective in inhibiting proliferation of AML, the concomitant inhibition of PI3K and mTOR by LY 294002 and rapamycin has more inhibitory effects on ATRA-mediated differentiation than the presence of PI3K-inhibitor alone, and diminishes positive effects of rapamycin on leukemia cell differentiation.
C1 [Mise, Josko] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Salata 3, 10 000 Zagreb, Croatia.
[Dembitz, Vilma] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Salata 3, 10 000 Zagreb, Croatia.
[Banfic, Hrvoje] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Salata 3, 10 000 Zagreb, Croatia.
[Visnjic, Dora] School of Medicine University of Zagreb, Croatian Institute for Brain Research, Salata 3, 10 000 Zagreb, Croatia.
RP Visnjic, D (reprint author), School of Medicine University of Zagreb, Croatian Institute for Brain Research, 10 000 Zagreb, Croatia.
EM visnjic@mef.hr
CR Xu Q, Simpson SE, Scialla TJ et al, 2003, Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood 102:972–980
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Sun SY, Rosenberg LM, Wang X et al, 2005, Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65:7052–7058
Tamburini J, Chapuis N, Bardet V et al, 2008, Mammalian target of rapamycin, mTOR, inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways. Blood 111:379–382
Carracedo A, Ma L, Teruya-Feldstein J et al, 2008, Inhibition of mTORC1 leads to MAPK pathway activation through a PI3Kdependent feedback loop in human cancer. J Clin Invest 118:3065–3074
Kinkade CW, Castillo-Martin M, Puzio-Kuter A et al, 2008, Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model. J Clin Invest 118:3051–3064
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Nishioka C, Ikezoe T, Yang J et al, 2009, Inhibition of mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells. Int J Cancer 125:1710–1720
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Ikezoe T, Nishioka C, Bandobashi K et al, 2007, Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells. Leuk Res 31:673–682
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Miranda MB, McGuire TF, Johnson DE, 2002, Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines. Leukemia 16:683–692
Crabbe T, Welham MJ, Ward SG, 2007, The PI3K inhibitor arsenal: choose your weapon! Trends Biochem Sci 32:450–456
Chiarini F, Fala F, Tazzari PL et al, 2009, Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia. Cancer Res 69:3520–3528
Park S, Chapuis N, Bardet V et al, 2008, PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia 22:1698–1706
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Park SJ, Kang SY, Kim NS et al, 2002, Phosphatidylinositol 3-kinase regulates PMA-induced differentiation and superoxide production in HL-60 cells. Immunopharmacol Immunotoxicol 24:211–226
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 645
EP 656
DI 10.1007/s12253-011-9365-z
PG 12
ER
PT J
AU Fang, Z
Xiong, Y
Li, J
Liu, L
Li, M
Zhang, W
Shi, L
Wan, J
AF Fang, Zhengyu
Xiong, Yi
Li, Jiana
Liu, Li
Li, Manhui
Zhang, Wei
Shi, Lei
Wan, Jun
TI Detection of APC Gene Deletions in Colorectal Malignancies Using Quantitative PCR in a Chinese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; APC; Copy number variation; Gene expression
ID Colorectal cancer; APC; Copy number variation; Gene expression
AB The adenomatous polyposis coli (APC) gene has been shown to be involved in genetic instability and to be downregluated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in colorectal cancers (CRCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of CRC and adjacent normal epithelium (n=134) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in colorectal malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage of colorectal cancer samples (26.1%, 35 out of 134). There was a positive correlation between copy number decrease of APC and tumor progression in CRCs. Furthermore, copy number loss of APC was correlated with decreased mRNA expression. However, mRNA levels of APC were also impaired in CRC samples with unaltered copy numbers, indicating that sporadic CRCs exhibit different mechanisms of APC regulation.
C1 [Fang, Zhengyu] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
[Xiong, Yi] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
[Li, Jiana] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
[Liu, Li] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
[Li, Manhui] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
[Zhang, Wei] Ji-Nan University, JNU-HKUST Joint LabGuangzhou, Guangdong, China.
[Shi, Lei] The Hong Kong University of Science and Technology, Division of Life Science, Section of Biochemistry and Cell BiologyKowloon, Hong Kong.
[Wan, Jun] Shenzhen-PKU-HKUST Medical Center, Biomedical Research InstituteShenzhen, Guangdong Province, China.
RP Wan, J (reprint author), Shenzhen-PKU-HKUST Medical Center, Biomedical Research Institute, Shenzhen, China.
EM wanj@ust.hk
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 657
EP 661
DI 10.1007/s12253-010-9359-2
PG 5
ER
PT J
AU Cserni, G
Francz, M
Kalman, E
Kelemen, Gy
Komjathy, CsD
Kovacs, I
Kulka, J
Sarkadi, L
Udvarhelyi, N
Vass, L
Voros, A
AF Cserni, Gabor
Francz, Monika
Kalman, Endre
Kelemen, Gyongyi
Komjathy, Csaba Detre
Kovacs, Ilona
Kulka, Janina
Sarkadi, Laszlo
Udvarhelyi, Nora
Vass, Laszlo
Voros, Andras
TI Estrogen Receptor Negative and Progesterone Receptor Positive Breast Carcinomas—How Frequent are they?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Estrogen receptor; Progesterone receptor; Immunohistochemistry; Estrogen receptor-negative progesterone receptor-positive breast cancer
ID Breast cancer; Estrogen receptor; Progesterone receptor; Immunohistochemistry; Estrogen receptor-negative progesterone receptor-positive breast cancer
AB Estrogen receptor (ER) testing has become an important part of breast cancer reporting as the ER status is a predictor of hormonal treatment efficacy. Progesteron receptors (PR) are often tested in parallel, and the best response to hormonal manipulations can be expected in tumors positive for both receptors. The existence of breast cancers with an ER negative and PR positive phenotype is controversial. A series of cases with this phenotype were reevaluated to clarify the existence and the frequency of this entity. A total of 205/6587 (3.1%; range of the rate per department: 0.3–7.1%.) cases reported to have the ER-negative and PR-positive status by immunohistochemistry were collected from 9 Hungarian departments. After careful reevaluation of the tumor slides and control tissues with a 1% cut-off for positivity and restaining of the questionable cases, all but 1 of the reevaluable 182 cases changed their original phenotype. Most cases converted to dual positives (n=124) or dual negatives (n=31) or unassessable / questionable. ER-negative and PR-positive breast cancers are very rare if existing. Such a phenotype should prompt reassessment.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Francz, Monika] Josa Andras Teaching Hospital, Department of Pathology, Szent Istvan u.68, 4400 Nyiregyhaza, Hungary.
[Kalman, Endre] University of Pecs, Department of Pathology, Szigeti ut 12, 7624 Pecs, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Komjathy, Csaba Detre] Kenezy Teaching Hospital, Department of Pathology, Bartok Bela u. 2-26, 4043 Debrecen, Hungary.
[Kovacs, Ilona] Kenezy Teaching Hospital, Department of Pathology, Bartok Bela u. 2-26, 4043 Debrecen, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Sarkadi, Laszlo] Kenezy Teaching Hospital, Department of Pathology, Bartok Bela u. 2-26, 4043 Debrecen, Hungary.
[Udvarhelyi, Nora] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy u.7-9, 1122 Budapest, Hungary.
[Vass, Laszlo] Flor Ferenc University Hospital of Pest County, Department. of Pathology/Cytopathology, Semmelweis ter 1, 2143 Kistarcsa, Hungary.
[Voros, Andras] University of Szeged, Department of Pathology, Allomas u. 2, 6720 Szeged, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, 6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Moshin SK, Weiss H, Havinghurst T et al, 2004, Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17:1545–1554
Viale G, Regan MM, Maiorano E et al, 2008, Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors—International Breast Cancer Study Group. J Clin Oncol 26:1404–1410
Nadji M, Gomez-Ferenandez C, Ganjei-Azar P et al, 2005, Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5, 993 breast cancers. Am J Clin Pathol 123:21–27
De Maeyer L, Van Limbergen E, De Nys K et al, 2008, Does estrogen receptor-negative/progesterone receptor-positive breast carcinoma exist? J Clin Oncol 26:335–340
Goldhirsch A, Glick JH, Gelber RD et al, 2005, Meeting highlights: International expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16:1569–1583
Rhodes A, Jasani B, 2009, The oestrogen receptor-negative/ progesterone receptor-positive breast tumour: a biological entity or a technical artefact? J Clin Pathol 62:95–96
Rakha EA, El-Sayed ME, Green AR et al, 2007, Biological and clinical characteristics of breast cancer with single hormone receptor-positive phenotype. J Clin Oncol 25:4772–4778
Hammond MEH, Hayes DF, Dowsett M et al, 2010, American Society of Clinical Oncology / College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795
Viale G, Regan MM, Maiorano E et al, 2007, Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 25:3846–3652
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 663
EP 668
DI 10.1007/s12253-011-9366-y
PG 6
ER
PT J
AU Golmoghaddam, H
Pezeshki, MA
Ghaderi, A
Doroudchi, M
AF Golmoghaddam, Hossein
Pezeshki, Mohammad Abdul
Ghaderi, Abbas
Doroudchi, Mehrnoosh
TI CD1a and CD1d Genes Polymorphisms in Breast, Colorectal and Lung Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD1; Allele; Breast cancer; Lung cancer; Colorectal cancer
ID CD1; Allele; Breast cancer; Lung cancer; Colorectal cancer
AB CD1 molecules might contribute to anti-tumor immune response by presentation of tumor-derived lipid and glycolipid antigens to T cells and NKT cells. Polymorphisms in CD1 genes have been suggested to modify ligand binding of CD1 molecules and thereby change the antigen presenting ability of these molecules. The aim of this study was to investigate the exon 2 polymorphisms of CD1a and CD1d in several high incident cancers in Iran. For this purpose, 201 female breast cancer patients and 207 healthy women, 64 lung cancer patients and 95 healthy individuals and 109 patients with colorectal cancer and 109 healthy controls were recruited to this study. Using PCR-SSP method, no significant correlation was found in genotype and allele frequencies of CD1a between all three studied groups and their control counterparts. Moreover, a dominant frequency of CD1d 01 (A) allele was observed in the majority of studied individuals. No significant association between the CD1 polymorphisms and prognostic factors in breast, lung and colorectal cancers was detected. Our results highlight the conserved nature of CD1 genes and may point to the immuoregulatory functions of CD1 molecules in cancer that can be exerted through fine tuning of NK, T and NKT cells.
C1 [Golmoghaddam, Hossein] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Pezeshki, Mohammad Abdul] Shiraz University of Medical Sciences, Institute for Cancer ResearchShiraz, Iran.
[Ghaderi, Abbas] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Doroudchi, Mehrnoosh] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Doroudchi, M (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM mdoroudchi@gmail.com
CR Mori L, De Libero G, 2008, Presentation of lipid antigens to T cells. Immunol Lett 117:1–8
Salio M, Silk JD, Cerundolo V, 2010, Recent advances in processing and presentation of CD1 bound lipid antigens. Curr Opin Immunol 22:81–8
De Libero G, Mori L, 2010, How the immune system detects lipid antigens. Prog Lipid Res 49:120–7
De Libero G, Mori L, 2005, Recognition of lipid antigens by T cells. Nat Rev Immunol 5:485–96
Coventry B, Heinzel S, 2004, CD1a in human cancers: a new role for an old molecule. Trends Immunol 25:242–8
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Metelitsa LS, Weinberg KI, Emanuel PD, Seeger RC, 2003, Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells. Leukemia 17:1068–77
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Yue SC, Shaulov A, Wang R et al, 2005, CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and production of bioactive IL-12. Proc Natl Acad Sci USA 102:11811–6
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 669
EP 675
DI 10.1007/s12253-011-9367-x
PG 7
ER
PT J
AU Pimentel-Nunes, P
Afonso, L
Lopes, P
Roncon-Albuquerque, R
Goncalves, N
Henrique, R
Moreira-Dias, L
Leite-Moreira, FA
Dinis-Ribeiro, M
AF Pimentel-Nunes, Pedro
Afonso, Luis
Lopes, Paula
Roncon-Albuquerque, Roberto
Goncalves, Nadia
Henrique, Rui
Moreira-Dias, Luis
Leite-Moreira, F Adelino
Dinis-Ribeiro, Mario
TI Increased Expression of Toll-like Receptors (TLR) 2, 4 and 5 in Gastric Dysplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric pathology; Dysplasia; Innate immunity receptors; TLRs
ID Gastric pathology; Dysplasia; Innate immunity receptors; TLRs
AB TLRs are important innate immunity receptors. Even though TLR2, 4 and 5 appear to be important for Helicobacter pylori (HP) recognition, their role in the evolution of gastritis to more advanced lesions is still unknown. To compare the expression of TLR2, 4 and 5 in normal gastric mucosa, HP+ gastritis, intestinal metaplasia, dysplasia and adenocarcinoma. Immunohistochemistry for TLR2, 4 and 5 was performed with anti-TLR2-TLR4-TLR5 antibodies in 117 histological samples of normal gastric mucosa (n=22), HP+ gastritis (n=20), intestinal metaplasia (n=33), dysplasia (mucosectomy specimens, n=20) and intestinal type adenocarcinoma (surgery specimens,n=22); quantification of expression was performed independently by two pathologists taking into account the percentage of positive epithelial cells and the degree of expression (zero to three score). A statistically significant trend for progressive increase of TLRs expression from normal mucosa to gastric dysplasia was found (mean expression: normal mucosa 0.1; gastritis 1.0; metaplasia 2.2; dysplasia 2.8, p<0.01). All dysplasia samples presented more than 90% positive epithelial cells with strong expression (2.8;95%CI2.7–3). There was less TLRs expression in carcinomas (TLR2:1.0; TLR4:2.0 and TLR5:1.2, p<0.05) when compared with dysplasia, with TLR4 being more expressed than TLR2 and 5 in these lesions (p=0.03). A score of all markers’ expression of eight leads to a low (4%) false positive rate in patients with precancerous conditions. Progression of gastric lesions associated with gastric carcinogenesis is associated with increased TLRs expression. Gastric dysplasia presents a high level of TLRs expression, suggesting that these receptors may play a role in adenocarcinoma development.
C1 [Pimentel-Nunes, Pedro] University of Porto, Cardiovascular Research & Development Unit, Al. Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
[Afonso, Luis] Portuguese Oncology Institute, Department of PathologyPorto, Portugal.
[Lopes, Paula] Portuguese Oncology Institute, Department of PathologyPorto, Portugal.
[Roncon-Albuquerque, Roberto] University of Porto, Cardiovascular Research & Development Unit, Al. Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
[Goncalves, Nadia] University of Porto, Cardiovascular Research & Development Unit, Al. Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
[Henrique, Rui] Portuguese Oncology Institute, Department of PathologyPorto, Portugal.
[Moreira-Dias, Luis] Portuguese Oncology Institute, Gastroenterology DepartmentPorto, Portugal.
[Leite-Moreira, F Adelino] University of Porto, Cardiovascular Research & Development Unit, Al. Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
[Dinis-Ribeiro, Mario] Portuguese Oncology Institute, Gastroenterology DepartmentPorto, Portugal.
RP Pimentel-Nunes, P (reprint author), University of Porto, Cardiovascular Research & Development Unit, 4200-319 Porto, Portugal.
EM pedronunesml@gmail.com
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la Trejo-de OA, Torres J, Perez-Rodriguez M, Camorlinga-Ponce M, Luna LF, Abdo-Francis JM et al, 2008, TLR4 single-nucleotide polymorphisms alter mucosal cytokine and chemokine patterns in Mexican patients with Helicobacter pylori-associated gastroduodenal diseases. Clin Immunol 129:333–340., DOI 10.1016/j.clim.2008.07.009
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Chochi K, Ichikura T, Kinoshita M, Majima T, Shinomiya N, Tsujimoto H et al, 2008, Helicobacter pylori augments growth of gastric cancers via the lipopolysaccharide-toll-like receptor 4 pathway whereas its lipopolysaccharide attenuates antitumor activities of human mononuclear cells. Clin Cancer Res 14:2909–2917., DOI 10.1158/1078-0432.CCR-07-4467
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 677
EP 683
DI 10.1007/s12253-011-9368-9
PG 7
ER
PT J
AU Gao, J
Zhang, J
Long, Y
Tian, Y
Lu, X
AF Gao, Jinbo
Zhang, Jinghui
Long, Yaoping
Tian, Yuan
Lu, Xiaoming
TI Expression of Tankyrase 1 in Gastric Cancer and Its Correlation with Telomerase Activity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tankyrase 1; Gastric cancer; Telomerase; Telomere
ID Tankyrase 1; Gastric cancer; Telomerase; Telomere
AB Tankyrase 1, which enhances telomerase access to telomeres, plays an important role in telomere maintenance. The aim of this study was to determine the expression and potential role of tankyrase 1 in gastric cancer development and progression. We examined the expression of tankyrase 1 by RT-PCR and Western blotting, and assessed telomerase activity by TRAP-ELISA method in gastric cancer and adjacent normal tissues. We found that tankyrase 1 expression was significantly up-regulated in gastric cancer tissues compared to normal corresponding tissues. Tankyrase 1 over-expression by gastric cancerous tissue was significantly associated with tumor histology differentiation and tumor stage. Moreover, tankyrase 1 expression was significantly correlation with telomerase activity. Our results indicate that tankyrase 1 overexpression may play an important role in gastric cancer development and progression. Tankyrase 1 may be used as a biomarker of gastric cancer and may serve as a target for cancer therapy.
C1 [Gao, Jinbo] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 1277 Jiefang Avenue, 430022 Wuhan, Hubei, China.
[Zhang, Jinghui] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 1277 Jiefang Avenue, 430022 Wuhan, Hubei, China.
[Long, Yaoping] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 1277 Jiefang Avenue, 430022 Wuhan, Hubei, China.
[Tian, Yuan] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 1277 Jiefang Avenue, 430022 Wuhan, Hubei, China.
[Lu, Xiaoming] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 1277 Jiefang Avenue, 430022 Wuhan, Hubei, China.
RP Gao, J (reprint author), Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of Surgery, 430022 Wuhan, China.
EM drgaojinbo@gmail.com
CR Zakian VA, 1995, Telomeres: beginning to understand the end. Science 270:1601–1607
Blackburn EH, 1991, Structure and function of telomeres. Nature 350:569–573
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB, 1992, Telomere end-replication problem and cell aging. J Mol Biol 225:951–960
Hanahan D, Weinberg RA, 2000, The hallmarks of cancer. Cell 100:57–70
Osterhage JL, Friedman KL, 2009, Chromosome end maintenance by telomerase. J Biol Chem 284:16061–16065
De Boeck G, Forsyth RG, Praet M, Hogendoorn PC, 2009, Telomere-associated proteins:cross-talk between telomere maintenance and telomere-lengthening mechanisms. J Pathol 217:327–344
Feng J, Funk WD, Wang SS et al, 1995, The RNA component of human telomerase. Science 269:1236–1241
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Smith S, de Lange T, 2000, Tankyrase promotes telomere elongation in human cells. Curr Biol 10:1299–1302
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Klapper W, Krams M, Qian W, Janssen D, Parwaresch R, 2003, Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomerebinding protein expression but uncoupled from proliferation. Br J Cancer 89:713–719
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Matsutani N, Yokozaki H, Tahara E et al, 2001, Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas. Int J Oncol 19:507–512
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Yoo J, Park SY, Kang SJ, Kim BK, Shim SI, Kang CS, 2003, Expression of telomerase activity, human telomerase RNA, and telomerase reverse transcriptase in gastric adenocarcinomas. Mol Pathol 16:700–707
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 685
EP 690
DI 10.1007/s12253-011-9369-8
PG 6
ER
PT J
AU Rijavec, M
Silar, M
Triller, N
Kern, I
Cegovnik, U
Kosnik, M
Korosec, P
AF Rijavec, Matija
Silar, Mira
Triller, Nadja
Kern, Izidor
Cegovnik, Urska
Kosnik, Mitja
Korosec, Peter
TI Expressions of Topoisomerase IIα and BCRP in Metastatic Cells are Associated with Overall Survival in Small Cell Lung Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Small cell lung cancer; Metastatic cells; Topoisomerase IIα; Breast cancer resistance protein (BCRP); mRNA expression levels
ID Small cell lung cancer; Metastatic cells; Topoisomerase IIα; Breast cancer resistance protein (BCRP); mRNA expression levels
AB The aim of this study was to investigate the mRNA expression levels of multidrug resistanceassociated proteins in chemo-naive metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemonaive metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.
C1 [Rijavec, Matija] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Silar, Mira] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Triller, Nadja] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Kern, Izidor] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Cegovnik, Urska] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Kosnik, Mitja] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
[Korosec, Peter] University Clinic of Respiratory and Allergic Diseases, Golnik 36, 4204 Golnik, Slovenia.
RP Rijavec, M (reprint author), University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia.
EM matija.rijavec@klinika-golnik.si
CR National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology: Small cell lung cancer. Available at: http://www.nccn.org/professionals/physician_gls/PDF/sclc.pdf. Accessed June 3, 2009
National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology: Non-Small cell lung cancer. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf. Accessed June 3, 2009
Scagliotti GV, Novello S, Selvaggi G, 1999, Multidrug resistance in non-small-cell lung cancer. Ann Oncol 10:S83–S86
Smith EF, Postmus PE, 1995, Chemotherapy of small cell lung cancer. In: Carney DN, ed, lung cancer. The Bath Press, Avon, pp 156–172
Ihde DC, Minna JD, 1991, Non-small cell lung cancer. Part I: biology, diagnosis, and staging. Curr Probl Cancer 15:61–104
Spiro SG, Porter JC, 2002, Lung cancer-where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 166:1166–1196
Ikuta K, Takemura K, Sasaki K, Kihara M, Nishimura M, Ueda N, Naito S, Lee E, Shimizu E, Yamauchi A, 2005, Expression of multidrug resistance proteins and accumulation of cisplatin in human non-small cell lung cancer cells. Biol Pharm Bull 28:707–712
Chhatriwala H, Jafri N, Salgia R, 2006, A review of topoisomerase inhibition in lung cancer. Cancer Biol Ther 5:1600–1607
Endicott JA, Ling V, 1989, The biochemistry of P-glycoproteinmediated multidrug resistance. Ann Rev Biochem 58:137–171
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Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD, 1998, A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665– 15670
Klein I, Sarkadi B, Varadi A, 1999, An inventory of the human ABC proteins. Biochim Biophys Acta 1461:237–262
Triller N, Korosec P, Kern I, Kosnik M, Debeljak A, 2006, Multidrug resistance in small cell lung cancer: expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease. Lung Cancer 54:235–240
Berger W, Elbling L, Micksche M, 2000, Expression of the major vault protein LRP in human non-small-cell lung cancer cells: activation by short-term exposure to antineoplastic drugs. Int J Cancer 88:293–300
Larsen AK, Escargueil AE, Skladanowski A, 2000, Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacol Ther 85:217–229
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Guinee DG Jr, Holden JA, Benfield JR, Woodward ML, Przygodzki RM, Fishback NF, Koss MN, Travis WD, 1996, Comparison of DNA topoisomerase II alpha expression in small cell and nonsmall cell carcinoma of the lung. In search of a mechanism of chemotherapeutic response. Cancer 78:729–735
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Goldman B, 2003, Multidrug resistance: can new drugs help chemotherapy score against cancer? J Natl Cancer Inst 95:255–257
Leonard GD, Fojo T, Bates SE, 2003, The role of ABC transporters in clinical practice. Oncologist 8:411–424
Kawabata S, Oka M, Soda H, Shiozawa K, Nakatomi K, Tsurutani J, Nakamura Y, Doi S, Kitazaki T, Sugahara K, Yamada Y, Kamihira S, Kohno S, 2003, Expression and functional analyses of breast cancer resistance protein in lung cancer. Clin Cancer Res 9:3052–3057
Kitazono M, Sumizawa T, Takebayashi Y, Chen ZS, Furukawa T, Nagayama S, Tani A, Takao S, Aikou T, Akiyama S, 1999, Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells. J Natl Cancer Inst 91:1647–1653
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 691
EP 696
DI 10.1007/s12253-011-9370-2
PG 6
ER
PT J
AU Duzcan, F
Duzcan, ES
Sen, S
Yorukoglu, K
Caner, V
Sen Turk, N
Cetin, OG
Kelten, C
Tuna, B
Sarsik, B
Tepeli, E
AF Duzcan, Fusun
Duzcan, Ender Suleyman
Sen, Sait
Yorukoglu, Kutsal
Caner, Vildan
Sen Turk, Nilay
Cetin, Ozan Gokhan
Kelten, Canan
Tuna, Burcin
Sarsik, Banu
Tepeli, Emre
TI Expression and Amplification of Topoisomerase-2α in Type 1 and Type 2 Papillary Renal Cell Carcinomas and Its Correlation with HER2/neu Amplification
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary renal cell carcinoma; Topoisomerase- 2α; HER2/neu; FISH; Immunohistochemistry
ID Papillary renal cell carcinoma; Topoisomerase- 2α; HER2/neu; FISH; Immunohistochemistry
AB The current study was undertaken to investigate chromosomal and genetical aberrations leading to overexpression of Topoisomerase-2α (TOP2α) and to reveal the possible association of these aberrations with HER2/neu overexpression and gene amplification, and to search for the relationship between TOP2α and HER2/neu status with prognostical biomarkers in papillary renal cell carcinoma (RCC), a group of tumors with diverse molecular, chromosomal and clinical features. Archival cases of papillary RCC obtained from Departments of Pathology of Pamukkale, Ege and Dokuz Eylul Universities were studied in two groups (type 1 and type 2) each containing 20 cases. The level of TOP2α and HER2/neu expression by tumor cells were determined immunohistochemically. A multicolor FISH probe was used to define both amplification of HER2/neu and TOP2α genes, and polysomy 17. The ratio of cells expressing TOP2α in type 1 and type 2 papillary RCC were 24.29% and 6.89%, respectively. The difference was statistically significant comparing the average or median values of groups separately (p=0.002). The expression levels of TOP2α and HER2/neu were also correlated. TOP2α and HER2/neu were co-amplified in both groups. Immunohistochemical expression was not observed in 15 of 23 cases with HER2/neu amplification. The most frequent finding detected by FISH method was polysomy of chromosome 17. We had contradictory results compared with the findings reported in the limited numbers of literature. It shows us that papillary RCC constitute a heterogenous group of tumors with various cytogenetic features and morphological classification of these tumors may not be compatible with their molecular characteristics.
C1 [Duzcan, Fusun] Pamukkale University, Medical Faculty, Department of Medical Genetics, Doktorlar Cad. Kat:3, BayramyeriDenizli, Turkey.
[Duzcan, Ender Suleyman] Pamukkale University, Faculty of Medicine, Department of PathologyDenizli, Turkey.
[Sen, Sait] Ege University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Yorukoglu, Kutsal] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Caner, Vildan] Pamukkale University, Medical Faculty, Department of Medical BiologyDenizli, Turkey.
[Sen Turk, Nilay] Pamukkale University, Faculty of Medicine, Department of PathologyDenizli, Turkey.
[Cetin, Ozan Gokhan] Pamukkale University, Medical Faculty, Department of Medical Genetics, Doktorlar Cad. Kat:3, BayramyeriDenizli, Turkey.
[Kelten, Canan] Pamukkale University, Faculty of Medicine, Department of PathologyDenizli, Turkey.
[Tuna, Burcin] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Sarsik, Banu] Ege University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Tepeli, Emre] Pamukkale University, Medical Faculty, Department of Medical Genetics, Doktorlar Cad. Kat:3, BayramyeriDenizli, Turkey.
RP Duzcan, F (reprint author), Pamukkale University, Medical Faculty, Department of Medical Genetics, Denizli, Turkey.
EM fusunduzcan@yahoo.com;fduzcan@pau.edu.tr
CR Eble J, Sauter G, Epstein J, Sesterhenn I, 2004, Tumours of the urinary system and male genital organs. In: Eble J, Sauter G, Epstein J, Sesterhenn I, eds, World health organization classification of tumours. IARC, Lyon, pp 27–29
Delahunt B, Eble JN, 1997, Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 10(6):537–544
Murphy WM, Grignon DJ, Perlman EJ, 2004, Tumors of the kidney, bladder and related urinary structures. AFIP atlas of tumor pathology, 4th series. American Registry of Pathology, Washington, pp 123–130
Petersen RO, Sesterhenn IA, Davis CJ, 2009, Urologic pathology, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, pp 54–56
Delahunt B, Eble J, McCredis M, Bethwaite P, Stewart J, Bilous M, 2001, Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases. Hum Pathol 32:590–595
Pignot G, Elie C, Conquy S et al, 2007, Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. Urology 69:230–235
Jiang F, Richter J, Schraml P, Bubendorf L, Gasser T, Sauter G, Mihatsch MJ, Moch H, 1998, Chromosomal imbalances in papillary renal cell carcinoma. Am J Pathol 153:1467–1473
Sanders ME, Mick R, Tomaszewski JE, Barr FG, 2002, Unique patterns of allelic imbalance distinguish type 1 from type 2 sporadic papillary renal cell carcinoma. Am J Pathol 161:997–1005
Kovacs G, Fuzesi L, Emanual A, Kung HF, 1991, Cytogenetics of papillary renal cell tumors. Genes Chromosom Cancer 3:249– 255
Glukhova L, Goguel AF, Chudoba I, Angevin E, Pavon C, Terrier-Lacombe MJ, Meddeb M, Escudier B, Bernheim A, 1998, Overpresentation of 7q31 and 17q in renal cell carcinomas. Genes Chromosom Cancer 22:171–178
Hughson MD, Dickman K, Bigler SA, Meloni AM, Sandberg AA, 1998, Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization. Cancer Genet Cytogenet 106:93–104
Hughson MD, Bigler S, Dickman K, Kovacs G, 1999, Renal cell carcinoma of end-stage renal disease: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification. Mod Pathol 12:301–309
Dekel Y, Frede T, Kugel V, Neumann G, Rassweiler J, Koren R, 2005, Human DNA topoisomerase II-alpha expression in laporospically treated renal cell carcinoma. Oncol Rep 14:271– 274
Cooper GM, Hausman RE, 2006, Genomik DNA’nin replikasyonu, korunmasi ve yeniden duzenlenmesi. In: Sakizli M, Atabey N, eds, Hucre-Molekuler Yaklasim. Translational, 3rd edn. Izmir Tip Kitapevi, Izmir, pp 186–187
Jarvinen TAH, Liu ET, 2003, Topoisomerase IIα gene, TOP2A, amplification and deletion in cancer—more common than anticipated. Cytopathology 14:309–313
Varis A, Wolf M, Monni O, Vakkari ML, Kokkola A, Moskalk C, Frierson H Jr, Powell SM, Knuutila S, Kalioniemi A, El-Rifai W, 2002, Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res 62:2625–2629
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Reese DM, Small EJ, Magrane G, Waldman FM, Chew K, Sudilovsky D, 2001, HER2 protein expression and gene amplification in androgen-independent prostate cancer. Am J Clin Pathol 116:234–239
Press MF, Finn RS, Cameron D, Di Leo A, Geyer CE, Villalobos IE, Santiago A, Guzman R, Gasparyan A, Ma Y, Danenberg K, Martin AM, Williams L, Oliva C, Stein S, Gagnon R, Arbushites M, Koehler MT, 2008, HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res 14:7861–7870
Caner V, Turk NS, Duzcan F, Tufan NL, Kelten EC, Zencir S, Dodurga Y, Bagci H, Duzcan SE, 2008, No strong association between HER-2/neu protein overexpression and gene amplification in high-grade invasive urothelial carcinomas. Pathol Oncol Res 14:261–266
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 697
EP 703
DI 10.1007/s12253-011-9372-0
PG 7
ER
PT J
AU Chu, T
Chen, X
Yu, J
Xiao, J
Fu, Z
AF Chu, Tongwei
Chen, Xiaoyang
Yu, Jie
Xiao, Jianwen
Fu, Zhou
TI Extracellular Matrix Metalloproteinase Inducer is a Negative Prognostic Factor of Pediatric Medulloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medulloblastoma; Extracellular matrix metalloproteinase inducer; Immunohistochemistry; Prognosis
ID Medulloblastoma; Extracellular matrix metalloproteinase inducer; Immunohistochemistry; Prognosis
AB Medulloblastoma (MB) is the most common embryonal CNS tumor of childhood. Its survival rates have significantly improved over the years due to developments in diagnostic techniques and therapeutic strategies. However, it is still an important cause of cancer-related deaths in children. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells. Therefore, the aim of this study was to investigate whether the expression patterns of EMMPRIN may predict the clinical prognosis in MB. EMMPRIN expression in a series of 56 MB with various grades and pathological types was analyzed by immunohistochemical staining on paraffin-embedded sections. Then, the correlation of EMMPRIN expression patterns with clinicalpathological features of patients and its prognostic relevance were determined. Immunohistochemistry revealed that the positive expression rate of EMMPRIN in MB (75.0%, 42/56) was significantly higher than that in normal cerebellums (6.7%, 2/30, p<0.001). In addition, EMMPRIN expression in MB was up-regulated in higher metastatic stage (p<0.01), aggressive histopathological type (p<0.005), necrosis (p<0.01), as well as with undifferentiated tumor (p<0.01). Furthermore, over-expression of EMMPRIN correlated significantly with poor prognosis (0.01 T KRAS transversion in patients with constitutional MUTYH biallelic mutations. Cancer Lett 274:266–270
Voz ML, Agten NS, Van de Ven WJ et al, 2000, PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Cancer Res 60:106–113
Van Dyck F, Declercq J, Braem CV et al, 2007, PLAG1, the prototype of the PLAG gene family: versatility in tumour development. Int J Oncol 30:765–774
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 765
EP 769
DI 10.1007/s12253-011-9384-9
PG 5
ER
PT J
AU Ngow, AH
Wan Khairina, MNW
AF Ngow, A Harris
Wan Khairina, Mohd Nowalid Wan
TI Cardiac Metastasis: A Rare Involvement of Primitive Neuroectodermal Tumour of the Lung
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE PNET; Cardiac Metastasis; Ewing’s Sarcoma; Extraosseous Ewing’s Sarcoma
ID PNET; Cardiac Metastasis; Ewing’s Sarcoma; Extraosseous Ewing’s Sarcoma
AB A 15 year-old adolescent was referred with 2 month history of worsening of breathlessness and haemoptysis. He also reported constitutional symptoms of fever, poor appetite and weight loss. The chest roentgenogram showed a massive right pleural effusion with apparent cardiomegaly. The cardiac silhouette over the right heart border was obliterated and the mediastinum was widened. Computed tomogram of the thorax showed a bulky heterogeneous mass in the right lung with extension to the heart. Subsequent CT guided lung biopsy revealed Primitive Neuroectodermal tumour (PNET). Here, we illustrate the clinical course of an aggressive pulmonary PNET with lethal cardiac metastasis.
C1 [Ngow, A Harris] International Islamic University Malaysia/Hospital Tengku Ampuan Afzan, Jalan Hospital, Kulliyyah of Medicine, 25150 Kuantan, Pahang, Malaysia.
[Wan Khairina, Mohd Nowalid Wan] Ministry of Health Malaysia, Hospital Tengku Ampuan Afzan, 25150 Kuantan, Pahang, Malaysia.
RP Ngow, AH (reprint author), International Islamic University Malaysia/Hospital Tengku Ampuan Afzan, Jalan Hospital, Kulliyyah of Medicine, 25150 Kuantan, Malaysia.
EM harrisngow@gmail.com
CR Besirli K, Arslan C, Tuzun H, Oz B, 2000, The primitive Neuroectodermal tumour of the heart. Eur J Cardiothorac Surg 18:619–621
Charney DA, Charney JM, Ghali VS, Teplitz C, 1996, Primitive Neuroectodermal tumour of the myocardium: a case report, review of the literature, immunohistochemical and ultrastructural study. Hum Pathol 27:1365–1369
Hendershot E, 2005, Treatment approaches for metastatic Ewing’s sarcoma: a review of the literature. J Pediatr Oncol Nurs 22:339– 352
Askin FB, Rosai J, Sibley RK, Dehner LP, McAlister WH, 1979, Malignant small cell tumour of the thoracopulmonary region in childhood. Cancer 43:2438–2451
Reynen K, Kockeritz U, Strasser RH, 2004, Metastases to the heart. Ann Oncol 15:375–381
Hawkins DS, Felgenhauer J, Park J, Kreissman S, Thomson B, Douglas J et al, 2002, Peripheral blood stem cell support reduces the toxicity of intensive chemotharpy for children and adolescents with metastatic sarcomas. Cancer 95:1354–1365
Marley EF, Liapis H, Humphry PA, Nadler RB, Siegel CL, Zhu X, Brandt SM, Dehner LP, 1997, Primitive Neuroectodermal tumor of the kidney another enigma: a pathologic, immunohistochemical and molecular diagnostic study. Am J Surg Pathol 21:354–359
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 771
EP 774
DI 10.1007/s12253-010-9328-9
PG 4
ER
PT J
AU Ioannidis, O
Papaemmanouil, S
Chatzopoulos, S
Paraskevas, G
Konstantara, A
Kotronis, A
Kakoutis, E
Makrantonakis, A
AF Ioannidis, Orestis
Papaemmanouil, Styliani
Chatzopoulos, Stavros
Paraskevas, George
Konstantara, Athina
Kotronis, Anastasios
Kakoutis, Emmanouil
Makrantonakis, Apostolos
TI Giant Bilateral Symptomatic Adrenal Myelolipomas Associated with Congenital Adrenal Hyperplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Adrenal gland; Bilateral myelolipomma; Congenital adrenal hyperplasia; 21-hydroxylase deficiency; Giant myelolipoma; Symptomatic myelolipoma
ID Adrenal gland; Bilateral myelolipomma; Congenital adrenal hyperplasia; 21-hydroxylase deficiency; Giant myelolipoma; Symptomatic myelolipoma
AB Adrenal myelolipoma is an uncommon, benign, biochemically non-functioning and endocrinologically inactive tumor composed of variable amounts of mature adipose tissue and scattered islands of haemopoietic elements, including erythroid, myeloid and lymphoid series, as well as megakaryocytes. Diagnosis of myelolipomas is based on imaging, with ultrasonography, CT and MRI being effective in more than 90% of cases. Differential diagnosis includes other containing fat adrenal masses such as teratoma, lipoma and liposarcoma. The optimal treatment depends on the size and symptoms of the myelolipoma. For incidentally discovered, asymptomatic adrenal myelolipomas smaller than 4 cm surveillance seems to be enough while symptomatic, complicated, hormonally active and larger than 7 cm myelolipomas, should be surgically removed. We present a case of giant bilateral symptomatic adrenal myelolipomas associated with congenital adrenal hyperplasia. A 34 year old female, with congenital adrenal hyperplasia because of 21-hydroxylase deficiency, presented with diffuse abdominal pain and vomiting. Physical examination revealed hirsutism, pronounced virilization and palpable masses both on the right and left abdominal area. The abdominal CT demonstrated bilateral large masses in the anatomical position of the adrenal glands with densities indicating adipose tissue. The differential diagnosis was between myelolipoma and liposarcoma. For diagnostic and also therapeutical reasons, as the masses were large and symptomatic and causing pressure to the surrounding structures, the patient was submitted to laparotomy for bilateral excision. Histopathological examination established the diagnosis of adrenal myelolipoma.
C1 [Ioannidis, Orestis] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Papaemmanouil, Styliani] General Regional Hospital ‘George Papanikolaou’, Department of PathologyThessaloniki, Greece.
[Chatzopoulos, Stavros] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Paraskevas, George] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Konstantara, Athina] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Kotronis, Anastasios] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Kakoutis, Emmanouil] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
[Makrantonakis, Apostolos] General Regional Hospital ‘George Papanikolaou’, First Surgical Department, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece.
RP Ioannidis, O (reprint author), General Regional Hospital ‘George Papanikolaou’, First Surgical Department, 54640 Thessaloniki, Greece.
EM telonakos@hotmail.com
CR Daneshmand S, Quek ML, 2006, Adrenal myelolipoma: diagnosis and management. Urol J 3:71–74
Osborn M, Smith M, Senbanjo T, Crofton M, Robinson S, Rajan P, 2002, Adrenal myelolipoma—clinical, radiological and cytological findings: a case report. Cytopathology 13:242–246
Cyran KM, Kenney PJ, Memel DS, Yacoub I, 1996, Adrenal myelolipoma. AJR Am J Roentgenol 166:395–400
Fujiwara R, Onishi T, Shimada A, Nakai T, Miyabo S, Nakakugi K, Yamamoto M, 1993, Adrenal myelolipoma: comparison of diagnostic imaging and pathological findings. Intern Med 32:166– 170
Talwalkar SS, Shaheen SP 2nd, 2006, Extra-adrenal myelolipoma in the renal hilum: a case report and review of the literature. Arch Pathol Lab Med 130:1049–1052
Lam KY, Lo CY, 2001, Adrenal lipomatous tumours: a 30 year clinicopathological experience at a single institution. J Clin Pathol 54:707–712
Repassy DL, Csata S, Sterlik G, Ivanyi A, 2001, Giant adrenal myelolipoma. Pathol Oncol Res 7:72–73
Nermoen I, Folling I, Vegge K, Larmo A, Nedrebo BG, Husebye ES, Lovas K, 2009, Two adults with adrenal myelolipoma and 21-hydroxylase deficiency. Case Report Med 2009:916891
Kalidindi RS, Hattingh L, 2006, Bilateral giant adrenal myelolipomas. Abdom Imaging 31:125–127
Palmer WE, Gerard-McFarland EL, Chew FS, 1991, Adrenal myelolipoma. AJR Am J Roentgenol 156:724
O’Daniel-Pierce ME, Weeks JA, McGrath PC, 1996, Giant adrenal myelolipoma. South Med J 89:1116–1118
Gould JD, Mitty HA, Pertsemlidis D, Szporn AH, 1987, Adrenal myelolipoma: diagnosis by fine-needle aspiration. AJR Am J Roentgenol 148:921–922
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 775
EP 778
DI 10.1007/s12253-010-9330-2
PG 4
ER
PT J
AU Tamas, L
Sari, E
Repassy, G
Szabo, P
Bagdi, E
Krenacs, L
Demeter, J
AF Tamas, Laszlo
Sari, Eszter
Repassy, Gabor
Szabo, Peter
Bagdi, Eniko
Krenacs, Laszlo
Demeter, Judit
TI Spontaneous Remission in Localized Diffuse Large B-cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Diffuse large B-cell lymphoma; Spontaneous remission; Activated B-cell type DLBLC; Root of tongue; Untreated lymphoma
ID Diffuse large B-cell lymphoma; Spontaneous remission; Activated B-cell type DLBLC; Root of tongue; Untreated lymphoma
AB Diffuse large B-cell lymphoma (DLBCL) is an aggressive neoplastic disease of the lymphatic system, the activated B-cell type of this disease is likely to have a substantially worse prognosis. In this study, we report the favorable outcome of the activated B-cell type of DLBCL, though untreated, 7 years after diagnosis. In 2003, DLBCL localized to the root of tongue was found in the patient complaining of dysphonia and a pharyngeal globus perception but the patient did not agree to get any active hematological treatment. During the following years, the patient did not have any complaints. At the otorhinolaryngological control examination, in 2010, she was complaintfree, had normal laboratory parameters. Moreover a PETCT scan did not reveal metabolic activity relating to malignancy. The extraordinary disease process can be explained by the spontaneous regression of the activated B-cell type DLBCL. Spontaneous regression of oral lymphoma has been published only exceptionally. To our knowledge, no report of spontaneous regression of activated B-cell type DLBLC has been reported.
C1 [Tamas, Laszlo] Jahn Ferenc South-Pest Hospital, Department of Oto-Rhino-Laryngology, Koves u. 1., 1204 Budapest, Hungary.
[Sari, Eszter] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Repassy, Gabor] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Szabo, Peter] PET-CT Medical Diagnostic LtdBudapest, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
RP Tamas, L (reprint author), Jahn Ferenc South-Pest Hospital, Department of Oto-Rhino-Laryngology, 1204 Budapest, Hungary.
EM tamlaci@freemail.hu
CR Alizadeh AA, Eisen MB, Davis RE et al, 2000, Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511
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Hans CP, Weisenburger DD, Greiner TC et al, 2004, Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282
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Abe R, Ogawa K, Maruyama Y et al, 2007, Spontaneous regression of diffuse large B-cell lymphoma harbouring epsteinbarr virus: a case report and review of the literature. J Clin Exp Hematopathol 47:23–26
Evans LS, Hancock B, 2003, Non-Hodgkin lymphoma. The Lancet Vol 362:139–146
Daly RM, Healy CM, Toner ME et al, 2008, Spontaneous regression of non-Hodgkin’s lymphoma int he oral cavity after incisional biopsy. Br J Or Maxillofac Surg 46:223–225
Savarrio L, Gibosn J, Dunlop DJ et al, 1999, Spontaneous regression of an anaplastic large cell lymphoma int he oral cavity: first reported case and review of the literature. Or Onc 35:609–613
Koga M, Kusukawa J, Havabuchi N, 2003, Spontaneous regression of extranodal malignant lymphoma occurred int he gingiva. Or Onc 39:323–324
Iqbal J, Greiner TC, Patel K et al, 2009, Gene expression profiling in lymphoma diagnosis and management. Best Pract & Res Clin Haem 22:191–210
Camilleri-Broet S, Criniere E, Broet P et al, 2006, A uniform activated B-cell-like immunophenotpye might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood 107:190–196
Lu X, Nechushtan H, Ding F et al, 2005, Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell like and activated B-cell –like diffuse large-cell lymphomas. Blood 105(7):2924–2932
Barrans SL, Carter I, Owen RG et al, 2002, Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood 99:1136–1143
Armitage JO, 2008, Is lymphoma occuring int he elderly the same disease? Leuk Lymphoma 49:14–6
Gutierrez A, Mestre F, Perez-Manga G, Rodriguez J, 2010, Diffuse large B-cell lymphoma in the older. Crit Rev Oncol HematolMar 18. [Epub ahead of print], DOI 10.1016/j.critrevonc.2010.02.009
Liu Y-H, Xu FP, Zhuang HG et al, 2008, Clinicopathologic significance of immunphenotypic profiles related to germinal center and activation B-cell differentiation in diffuse large B-cell lymphoma from Chinese patients. Hum Path 39:875–884
Pfreundschuh M, 2010, How I treat elderly patients with diffuse large B-cell lymphoma. Blood 116:5103–10
Miller TP, Unger JM, Spier CM et al, 2004, Effect of adding rituximab to three cycles of CHOP plus involved –field radiotherapy for limited –stage agressive diffuse B-cell lymphoma, SWOG-0014). Blood 104:48a
Persky DO, Unger JM, Spier CM et al, 2008, Phase II study of rituximab plus three cycles of CHOP and involved –field radiotherapy for patients with limited-stage agressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol 26(14):2258–2263
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2011
VL 17
IS 3
BP 779
EP 784
DI 10.1007/s12253-011-9379-6
PG 6
ER
PT J
AU Sikalidis, KA
Varamini, B
AF Sikalidis, K Angelos
Varamini, Behzad
TI Roles of Hormones and Signaling Molecules in Describing the Relationship Between Obesity and Colon cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Colon cancer; Inflammation; Insulin; Leptin; Obesity
ID Colon cancer; Inflammation; Insulin; Leptin; Obesity
AB Colon cancer represents a highly prevalent disease in the Western world. While dietary and lifestyle recommendations remain important factors in disease prevention and treatment, epidemiological data have made it clear that obesity and excess body weight remain significant risk factors for the disease. A number of potential direct and indirect relationships exist between obesity and increased risk of colon cancer. Several mechanisms which appear promising and warrant further investigation are discussed here, specifically the modifying role of insulin and insulin-like growth factors, leptin, adipose-tissue induced changes in estrogens and androgens, and inflammatory molecules. A brief review of these hormones and signaling molecules and their action in colon cancer development is described. A thorough integration and understanding of the mechanisms of action these systems exert on colonic epithelia will be important in designing studies and experiments aimed at elucidating disease etiology for prevention and treatment.
C1 [Sikalidis, K Angelos] Cornell University, Division of Nutritional Sciences, 214 Savage Hall, 14853 Ithaca, NY, USA.
[Varamini, Behzad] University of Pennsylvania, School of Medicine, 19104 Philadelphia, PA, USA.
RP Sikalidis, KA (reprint author), Cornell University, Division of Nutritional Sciences, 14853 Ithaca, USA.
EM as545@cornell.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 785
EP 790
DI 10.1007/s12253-010-9352-9
PG 6
ER
PT J
AU Dunai, Zs
Bauer, IP
Mihalik, R
AF Dunai, Zsuzsanna
Bauer, I Pal
Mihalik, Rudolf
TI Necroptosis: Biochemical, Physiological and Pathological Aspects
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Necrosis; Necroptosis; Programmed cell death; RIPK1; RIPK3; TNF; Death receptor
ID Necrosis; Necroptosis; Programmed cell death; RIPK1; RIPK3; TNF; Death receptor
AB Programmed cell death is a key component of tissue homeostasis, normal development and wide variety of diseases. Conventional view refers to programmed cell death form as caspase-mediated apoptosis while necrosis is considered as an accidental and unwanted cell demise, carried out in a non-regulated manner and caused by extreme conditions. However, accumulating evidences indicate that necrotic cell death can also be a regulated process. The term necroptosis has been introduced to describe a cell death receptor-induced, caspase-independent, highly regulated type of programmed cell death process with morphological resemblance of necrosis. Necroptosis recently has been found to contribute to a wide range of pathologic cell death forms including ischemic brain injury, neurodegenerative diseases and viral infection, therefore a better understanding of the necroptotic signaling machinery has clinical relevance.
C1 [Dunai, Zsuzsanna] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy street 7-9, H-1122 Budapest, Hungary.
[Bauer, I Pal] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Tuzolto street 37-47, H-1094 Budapest, Hungary.
[Mihalik, Rudolf] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Rath Gyorgy street 7-9, H-1122 Budapest, Hungary.
RP Dunai, Zs (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, H-1122 Budapest, Hungary.
EM dunaizs@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 791
EP 800
DI 10.1007/s12253-011-9433-4
PG 10
ER
PT J
AU Vicha, A
Holzerova, M
Krepelova, A
Musil, Z
Prochazka, P
Sumerauer, D
Kodet, R
Eckschlager, T
Jarosova, M
AF Vicha, Ales
Holzerova, Milena
Krepelova, Anna
Musil, Zdenek
Prochazka, Pavel
Sumerauer, David
Kodet, Roman
Eckschlager, Tomas
Jarosova, Marie
TI Molecular Cytogenetic Characterization in Four Pediatric Pheochromocytomas and Paragangliomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pheochromocytoma; Paraganglioma; Comparative genomic hybridization; Pediatric; Microarray
ID Pheochromocytoma; Paraganglioma; Comparative genomic hybridization; Pediatric; Microarray
AB Pheochromocytomas (PCCs) are rare tumors among children and adolescents and therefore are not genetically well characterized. The most frequently observed chromosomal changes in PCC are losses of 1p, 3q and/or 3p, 6q, 17p, 11q, 22q, and gains of 9q and 17q. Aberrations involving chromosome 11 are more common in malignant tumors. Unfortunately information about gene aberrations in childhood PCC’s is limited. We used comparative genomic hybridization (CGH) and array comparative genomic hybridization (aCGH) to screen for copy number changes in four children suffering from pheochromocytoma or paraganglioma. Patients were diagnosed at the age 13 or 14 years. Bilateral pheochromocytoma was associated with von Hippel-Lindau syndrome (VHL). Multiple paraganglioma was associated with a germline mutation in SDHB. We found very good concordance between the results of CGH and aCGH techniques. Losses were observed more frequently than gains. All cases had a loss of chromosome 11 or 11p. Other aberrations were loss of chromosome 3 and 11 in sporadic pheochromocytoma, and loss of 3p and 11p in pheochromocytoma, which carried the VHL mutation. The deletion of chromosome 1p and other changes were observed in paragangliomas. We conclude that both array CGH and CGH analysis identified similar chromosomal regions involved in tumorigenesis of pheochromocytoma and paragangliomas, but we found 3 discrepancies between the methods. We didn’t find any, of the proposed, molecular markers of malignancy in our benign cases and therefore we speculate that molecular cytogenetic examination may be helpful in separating benign and malignant forms in the future.
C1 [Vicha, Ales] Charles University, 2nd Medical School and University Hospital Motol, Department of Pediatric Hematology and Oncology, Fakultni nemocnice v Motole, V uvalu 84Prague, Czech Republic.
[Holzerova, Milena] Palacky University and University Hospital, Medical School, Department of Hemato-oncologyOlomouc, Czech Republic.
[Krepelova, Anna] Charles University and University Hospital Motol, 2nd Medical School, Institute of Biology and Medical GeneticsPrague, Czech Republic.
[Musil, Zdenek] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Institute of Biology and Medical GeneticsPrague, Czech Republic.
[Prochazka, Pavel] Charles University, 2nd Medical School and University Hospital Motol, Department of Pediatric Hematology and Oncology, Fakultni nemocnice v Motole, V uvalu 84Prague, Czech Republic.
[Sumerauer, David] Charles University, 2nd Medical School and University Hospital Motol, Department of Pediatric Hematology and Oncology, Fakultni nemocnice v Motole, V uvalu 84Prague, Czech Republic.
[Kodet, Roman] Charles University and University Hospital Motol, 2nd Medical School, Department of Pathology and molecular medicinePrague, Czech Republic.
[Eckschlager, Tomas] Charles University, 2nd Medical School and University Hospital Motol, Department of Pediatric Hematology and Oncology, Fakultni nemocnice v Motole, V uvalu 84Prague, Czech Republic.
[Jarosova, Marie] Palacky University and University Hospital, Medical School, Department of Hemato-oncologyOlomouc, Czech Republic.
RP Vicha, A (reprint author), Charles University, 2nd Medical School and University Hospital Motol, Department of Pediatric Hematology and Oncology, Prague, Czech Republic.
EM ales.vicha@lfmotol.cuni.cz
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 801
EP 808
DI 10.1007/s12253-011-9385-8
PG 8
ER
PT J
AU Rykala, J
Przybylowska, K
Majsterek, I
Pasz-Walczak, G
Sygut, A
Dziki, A
Kruk-Jeromin, J
AF Rykala, Jan
Przybylowska, Karolina
Majsterek, Ireneusz
Pasz-Walczak, Grazyna
Sygut, Andrzej
Dziki, Adam
Kruk-Jeromin, Julia
TI Angiogenesis Markers Quantification in Breast Cancer and Their Correlation with Clinicopathological Prognostic Variables
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Angiogenesis; Cancer progression; Multiplex protein assay
ID Breast cancer; Angiogenesis; Cancer progression; Multiplex protein assay
AB Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay can improve diagnosis and prognosis in this diseases.
C1 [Rykala, Jan] Medical University of Lodz, Barlicki Hospital, Department of Plastic, Reconstructive and Aesthetic Surgery, Kopcinskiego 22, 90–153 Lodz, Poland.
[Przybylowska, Karolina] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Hallera 1, 90–647 Lodz, Poland.
[Majsterek, Ireneusz] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Hallera 1, 90–647 Lodz, Poland.
[Pasz-Walczak, Grazyna] Medical University of Lodz, Department of Pathology, Paderewskiego 4, 93–509 Lodz, Poland.
[Sygut, Andrzej] Medical University of Lodz, Department of General and Colorectal Surgery, Hallera 1, 90–647 Lodz, Poland.
[Dziki, Adam] Medical University of Lodz, Department of General and Colorectal Surgery, Hallera 1, 90–647 Lodz, Poland.
[Kruk-Jeromin, Julia] Medical University of Lodz, Barlicki Hospital, Department of Plastic, Reconstructive and Aesthetic Surgery, Kopcinskiego 22, 90–153 Lodz, Poland.
RP Rykala, J (reprint author), Medical University of Lodz, Barlicki Hospital, Department of Plastic, Reconstructive and Aesthetic Surgery, 90–153 Lodz, Poland.
EM janekrykalarykala@gmail.com
CR Baeriswyl V, Christofori G, 2009, The angiogenic switch in carcinogenesis. Semin Cancer Biol 19(5):329–337
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A Randomized Phase III Trial of Paclitaxel With or Without Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer: Eastern Cooperative Oncology Group trial E 2100. Abstract 7
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 809
EP 817
DI 10.1007/s12253-011-9387-6
PG 9
ER
PT J
AU Naghibalhossaini, F
Hosseini, MH
Mokarram, P
Zamani, M
AF Naghibalhossaini, Fakhraddin
Hosseini, Mahmoodzadeh Hamideh
Mokarram, Pooneh
Zamani, Mozhdeh
TI High Frequency of Genes’ Promoter Methylation, but Lack of BRAF V600E Mutation among Iranian Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancer; BRAF; KRAS; Methylation
ID Colon cancer; BRAF; KRAS; Methylation
AB Gene silencing due to DNA hypermethylation is a major mechanism for loss of tumor suppressor genes function in colorectal cancer. Activating V600E mutation in BRAF gene has been linked with widespread methylation of CpG islands in sporadic colorectal cancers. The aim of the present study was to evaluate the methylation status of three cancer-related genes, APC2, p14ARF, and ECAD in colorectal carcinogenesis and their association with the mutational status of BRAF and KRAS among Iranian colorectal cancer patients. DNA from 110 unselected series of sporadic colorectal cancer patients was examined for BRAF V600E mutation by PCR-RFLP. Promoter methylation of genes in tumors was determined by methylation specific PCR. The frequency of APC2, E-CAD, and p14 methylation was 92.6%, 40.4% and 16.7%, respectively. But, no V600E mutation was identified in the BRAF gene in any sample. No association was found in cases showing epigenetic APC, ECAD, and p14 abnormality with the clinicopathological parameters under study. The association between KRAS mutations and the so called methylator phenotype was previously reported. Therefore, we also analyzed the association between the hot spot KRAS gene mutations in codons of 12 and 13 with genes’ promoter hypermethylation in a subset of this group of patients. Out of 86 tumors, KRAS was mutated in 24 (28%) of tumors, the majority occurring in codon 12. KRAS mutations were not associated with genes’ methylation in this tumor series. These findings suggest a distinct molecular pathway for methylation of APC2, p14, and ECAD genes from those previously described for colorectal cancers with BRAF or KRAS mutations.
C1 [Naghibalhossaini, Fakhraddin] Shiraz University of Medical Sciences, Department of Biochemistry, Zand StreetShiraz, Fars, Iran.
[Hosseini, Mahmoodzadeh Hamideh] Shiraz University of Medical Sciences, Department of Biochemistry, Zand StreetShiraz, Fars, Iran.
[Mokarram, Pooneh] Shiraz University of Medical Sciences, Department of Biochemistry, Zand StreetShiraz, Fars, Iran.
[Zamani, Mozhdeh] Shiraz University of Medical Sciences, Department of Biochemistry, Zand StreetShiraz, Fars, Iran.
RP Naghibalhossaini, F (reprint author), Shiraz University of Medical Sciences, Department of Biochemistry, Shiraz, Iran.
EM fakhraddin.naghibalhossaini@mail.mcgill.ca
CR Malekzadeh R, Bishehsari F, Mahdavinia M, Ansari R, 2009, Epidemiology and molecular genetics of colorectal cancer in Iran: a review. Arch Iran Med 12:161–169
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 819
EP 825
DI 10.1007/s12253-011-9388-5
PG 7
ER
PT J
AU Patara, M
Santos, MME
Coudry, dAR
Soares, AF
Ferreira, OF
Rossi, MB
AF Patara, Marcelo
Santos, Maria Monteiro Erika
Coudry, de Almeida Renata
Soares, Augusto Fernando
Ferreira, Oliveira Fabio
Rossi, Mauro Benedito
TI Ezrin Expression as a Prognostic Marker in Colorectal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Ezrin; Biological marker; Prognostic; Adenocarcinoma
ID Colorectal cancer; Ezrin; Biological marker; Prognostic; Adenocarcinoma
AB Ezrin protein acts in the regulation of cytoskeletal and directly influences survival and tumor progression; there is an increase in its expression in metastatic cells and tissues in several types of cancer including colorectal cancer. 250 Patients with colorectal cancer submitted to surgery from 1995 to 2002. Protein expression was carried through by Tissue Micro Array immunohistochemical tests of paraffined neoplasic tissues and associated with clinical variables. Differentiation degree, lymph node invasion, metastasis at diagnosis, and palliative surgery were associated to a higher expression of the protein and survival. Higher expression of the Ezrin correlates with tumor aggressiveness and worse prognosis for colorectal cancer.
C1 [Patara, Marcelo] College of Medical Sciences Santa Casa de Sao Paulo, CNPq—PIBIC, Rua Professor Antonio Prudente, 211, 01509–010 Sao Paulo, SP, Brazil.
[Santos, Maria Monteiro Erika] Hospital A.C.Camargo, Center of ResearchSao Paulo, Brazil.
[Coudry, de Almeida Renata] A. C. Camargo Cancer Hospital, Department of PathologySao Paulo, Brazil.
[Soares, Augusto Fernando] A. C. Camargo Cancer Hospital, Department of PathologySao Paulo, Brazil.
[Ferreira, Oliveira Fabio] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery DepartmentSao Paulo, Brazil.
[Rossi, Mauro Benedito] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery DepartmentSao Paulo, Brazil.
RP Patara, M (reprint author), College of Medical Sciences Santa Casa de Sao Paulo, CNPq—PIBIC, 01509–010 Sao Paulo, Brazil.
EM marcelopatara@gmail.com
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Kobel M, Langhammer T, Huttelmaier S, Schmitt WD, Kriese K, Dittmer J, Strauss HG, Thomssen C, Hauptmann S, 2006, Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas. Mod Pathol 19:581–7
Ohtani K, Sakamoto H, Rutherford T, Chen Z, Satoh K, Naftolin F, 1999, Ezrin, a membrane-cytoskeletal linking protein, is involved in the process of invasion of endometrial cancer cells. Cancer Lett 147:31–8
Ohtani K, Sakamoto H, Rutherford T, Chen Z, Kikuchi A, Yamamoto T, Satoh K, Naftolin F, 2002, Ezrin, a membranecytoskeletal linking protein, is highly expressed in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma. Cancer Lett 179:79–86
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Makitie T, Carpen O, Vaheri A, Kivela T, 2001, Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma. Invest Ophthalmol Vis Sci 42:2442–2448
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Curto M, Al McClatchey, 2004, Ezrin. A metastatic determinant? Cancer Cell 5:113–14
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 827
EP 833
DI 10.1007/s12253-011-9389-4
PG 7
ER
PT J
AU Hata, M
Machi, J
Mamou, J
Yanagihara, TE
Saegusa-Beecroft, E
Kobayashi, KG
Wong, CMC
Fung, C
Feleppa, JE
Sakamoto, K
AF Hata, Masaki
Machi, Junji
Mamou, Jonathan
Yanagihara, T Eugene
Saegusa-Beecroft, Emi
Kobayashi, K Gregory
Wong, C M Clifford
Fung, Conway
Feleppa, J Ernest
Sakamoto, Kazuhiro
TI Entire-volume Serial Histological Examination for Detection of Micrometastases in Lymph Nodes of Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Lymph nodes; Micrometastases; Serial histological examination
ID Colorectal cancer; Lymph nodes; Micrometastases; Serial histological examination
AB The purpose of this study was to accurately detect lymph-node micrometastases, i.e., metastatic cancer foci that have a size between 2.0 and 0.2 mm, in nodes excised from colorectal cancer (CRC) patients, and to determine how frequently micrometastases might be missed when standard histological examination procedures are used. A total of 311 lymph nodes were removed and examined from 90 patients with Stage I to IV CRC. The number of slices of histology sections ranged from 6 to 75 per node (average=25.5; SD=11.1), which provided a total of 7,943 slices. Lymph nodes were examined in their entire volume at every 50-μm and 100-μm intervals for nodes smaller and larger than 5 mm respectively. The total number of thin sections examined in each node and the number of thin sections where metastatic foci were present were counted. The number of thin sections with metastatic foci and the total number of slices was determined for each node. In addition, the presence or absence of metastatic foci in the "central" slice was determined. Micrometastases were found in 12/311 (3.9%) of all lymph nodes. In the 12 lymph nodes with micrometastases, the rate of metastatic slices over all slices was 39.4% (range=6.3 to 81.3%; SD=25.8%) In the central slice of each node, micrometastases were present only in 6 of 12 lymph nodes (50%); accordingly, they were not present in the central slice for half the micrometastatic nodes. These 6 nodes represented 1.9% of the 311 nodes and 11.1% of the 54 metastatic nodes. This study suggests that a significant fraction of micrometastases can be missed by traditional singleslice sectioning; half of the micrometastases would have been overlooked in our data set of 311 nodes.
C1 [Hata, Masaki] University of Hawaii and Kuakini Medical Center, Department of Surgery, 405 N. Kuakini Street, Suite 601, 96817 Honolulu, HI, USA.
[Machi, Junji] University of Hawaii and Kuakini Medical Center, Department of Surgery, 405 N. Kuakini Street, Suite 601, 96817 Honolulu, HI, USA.
[Mamou, Jonathan] Riverside Research InstituteNew York, NY, USA.
[Yanagihara, T Eugene] University of Hawaii and Kuakini Medical Center, Department of PathologyHonolulu, HI, USA.
[Saegusa-Beecroft, Emi] University of Hawaii and Kuakini Medical Center, Department of Surgery, 405 N. Kuakini Street, Suite 601, 96817 Honolulu, HI, USA.
[Kobayashi, K Gregory] University of Hawaii and Kuakini Medical Center, Department of PathologyHonolulu, HI, USA.
[Wong, C M Clifford] University of Hawaii and Kuakini Medical Center, Department of PathologyHonolulu, HI, USA.
[Fung, Conway] University of Hawaii and Kuakini Medical Center, Department of PathologyHonolulu, HI, USA.
[Feleppa, J Ernest] Riverside Research InstituteNew York, NY, USA.
[Sakamoto, Kazuhiro] Juntendo University School of Medicine, Department of Coloproctological SurgeryTokyo, Japan.
RP Hata, M (reprint author), University of Hawaii and Kuakini Medical Center, Department of Surgery, 96817 Honolulu, USA.
EM masakihata4999@yahoo.co.jp
CR Greene FL, Page DL, Fleming ID et al, 2002, AJCC cancer staging manual. 6th ed. New York Springer;.
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Tan LK, Giri D, Hummer AJ et al, 2008, Occult Axillary Node Metastases in Breast Cancer Are Prognostically Significant: Results in 368 Node-Negative Patients With 20-Year Follow-Up. J Clin Oncol 26:1803–1809
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Reed J, Rosman M, Verbanac KM et al, 2009, Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer: 10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/ Anne Arundel Medical Center Sentinel Node Multicenter Study. J Am Coll Surg 208:333–340
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Fisher ER, Colangelo L, Wieand S et al, 2003, Lack of influence of cytokeratin-positive mini micrometastases in “negative node” patients with colorectal cancer: findings from the National Surgical Adjuvant Breast and Bowel Projects protocols R-01 and C-01. Dis Colon Rectum 46:1021–1026
Noura S, Yamamoto H, Miyake Y et al, 2002, Immunohistochemical assessment of localization and frequency of micrometastasis in lymph nodes of colorectal cancer. Clin Cancer Res 8:759–767
Palma RT, Waisberg J, Bromberg SH et al, 2003, Micrometastasis in regional lymph nodes of extirpated colorectal carcinoma: immunohistochemical study using anti-cytokeratin antibodies AE1/AE3. Colorectal Dis 5:164–168
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Messerini L, Cianchi F, Cortesini C et al, 2006, Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma. Hum Pathol 37:1259–1267
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Pheby D, Levine D, Pitcher R et al, 2004, Lymph-node harvests directly influence the staging of colorectal cancer: evidence of a regional audit. J Clin Pathol 57:43–47
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 835
EP 841
DI 10.1007/s12253-011-9390-y
PG 7
ER
PT J
AU Kandemir, ON
Barut, F
Gun, DB
Keser, HS
Karadayi, N
Gun, M
Ozdamar, OS
AF Kandemir, Onak Nilufer
Barut, Figen
Gun, Dogan Banu
Keser, Hallac Sevinc
Karadayi, Nimet
Gun, Mustafa
Ozdamar, Oguz Sukru
TI Lymphatic Differentiation in Classic Kaposi’s Sarcoma: Patterns of D2-40 Immunoexpression in the Course of Tumor Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE D2-40; Immunohistochemistry; Kaposi sarcoma; Lymphatic; Podoplanin
ID D2-40; Immunohistochemistry; Kaposi sarcoma; Lymphatic; Podoplanin
AB The recent development of lymphatic endotheliumspecific immuno-indicators has given rise to research on the histogenesis of Kaposi sarcoma (KS), specifically focusing on its lymphatic root and differentiation. D2-40 is a new lymphatic marker that recognizes podoplanin and is easily applied to formalin-fixed paraffin-embedded human tissues. This study examined D2-40 immunoexpression in 178 classical KS lesions using immunohistochemical methods. D2-40 immunoexpression was also examined in 63 non-KS soft tissue lesions to test the reliability of D2-40 monoclonal antibody in the pathological diagnosis of KS. D2-40 immunoreactivity was detected at all of the KS lesions and in lymphangioma and nonneoplastic lymphatic endothelium. There was no significant relationship between the extent of D2-40 staining and histopathological stage; however, there was a positive correlation between the staining intensity and histopathological stage in KS cases. D2-40 immunoreactivity was detected at all histopathological stages of KS and may be added to the routine immunohistochemical panel used for the differential diagnosis of KS. Widespread D2-40 protein expression is evidence of a lymphatic origin or the differentiation of neoplastic cells in KS, and D2-40 expression increases with tumor progression.
C1 [Kandemir, Onak Nilufer] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
[Barut, Figen] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
[Gun, Dogan Banu] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
[Keser, Hallac Sevinc] Lutfi Kirdar Kartal Training and Research Hospital, Department of PathologyIstanbul, Turkey.
[Karadayi, Nimet] Lutfi Kirdar Kartal Training and Research Hospital, Department of PathologyIstanbul, Turkey.
[Gun, Mustafa] Ataturk State Hospital, Department of PathologyZonguldak, Turkey.
[Ozdamar, Oguz Sukru] Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Zonguldak, Turkey.
RP Kandemir, ON (reprint author), Zonguldak Karaelmas University, School of Medicine, Department of Pathology, 67600 Kozlu, Turkey.
EM niluferkandemir@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 843
EP 851
DI 10.1007/s12253-011-9392-9
PG 9
ER
PT J
AU Szabo, VG
Acsady, Gy
AF Szabo, Viktor Gabor
Acsady, Gyorgy
TI Tumornecrosis-Factor-α 308 GA Polymorphism in Atherosclerotic Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumornecrosis-factor-α; Polymorphism; Atherosclerosis; Cardiovascular risk
ID Tumornecrosis-factor-α; Polymorphism; Atherosclerosis; Cardiovascular risk
AB The development of the atherosclerosis is a multifactorial process, where the clinical pattern is determined by environmental and genetic factors. Except for the classical risk factors of atherosclerosis (hypertension, lipid-metabolic disorders, diabetes, smoking) the clinical signs can be influenced by the genetic variants (polymorphisms) of the enzymes, which are responsible for the endothelial cell function and for the thrombotic factors. In our examination our aim was to define the TNF-α 308GA polymorphisms in atherosclerotic diabetic, atherosclerotic non-diabetic and healthy patients. We found correlation of the frequency of myocardial infarction and stroke in atherosclerotic diabetic and atherosclerotic non-diabetic patients. We proved that among patients with mutant TNF-α AA genotype the occurrence of cardiovascular events is significantly higher: Mutant AA homozygous genotype: control group 1, 6%, MI group 10,7%, p<0,005, OR: 8,17 versus Normal GG allele: control group 76,7%, MI group 61,3%. The TNF-α AA genotype can have a clinical importance as a prognostic and therapeutic marker, although further studies are needed to confirm this hypothesis.
C1 [Szabo, Viktor Gabor] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor str. 68, 1122 Budapest, Hungary.
[Acsady, Gyorgy] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor str. 68, 1122 Budapest, Hungary.
RP Szabo, VG (reprint author), Semmelweis University, Department of Cardiovascular Surgery, 1122 Budapest, Hungary.
EM szabogvdr@gmail.com
CR Yang Z, Ming X, 2006, Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin Med Res 4, 1):53–65
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 853
EP 857
DI 10.1007/s12253-011-9393-8
PG 5
ER
PT J
AU Liu, Dc
Yang, ZL
Jiang, S
AF Liu, Dong-cai
Yang, Zhu-Lin
Jiang, Song
TI Identification of PEG10 and TSG101 as Carcinogenesis, Progression, and Poor-Prognosis Related Biomarkers for Gallbladder Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder cancer; Gallbladder polyp; Chronic cholecystitis; PEG10; TSG101
ID Gallbladder cancer; Gallbladder polyp; Chronic cholecystitis; PEG10; TSG101
AB PEG10 is a transcriptional factor while TSG101 is involved in numerous cellular processes, including apoptotic resistance. Overexpression of PEG10 and TSG101 were observed in a variety of human cancers. However, their expression and clinical significance in gallbladder cancer (GBC) have not yet been identified. To understand the tumor biology of GBC at the molecular level, we examined PEG10 and TSG101 expression in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues by using immunohistochemistry. Overexpression of PEG10 and TSG101 was detected in gallbladder adenocarcinoma (48.1% and 47.2%, respectively). Conversely, there was less expression detected in the peritumoral tissues (19.6%), adenomatous polyps (13.3%), and gallbladder epithelium with chronic cholecystitis (5.1%) (p<0.01, p<0.05, and p<0.01, respectively). Notably, the benign lesions with positive PEG10 and/or TSG101 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The overexpression of PEG10 and TSG101 was significantly associated with differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that overexpression of PEG10 (p=0.041) and TSG101 (p=0.025) was closely associated with decreased overall survival. Multivariate Cox regression analysis revealed that positive expression of PEG10 (p=0.036) or TSG101 (p=0.022) is a predictor of poor prognosis in gallbladder adenocarcinoma. Our study suggested that overexpression of PEG10 and TSG101 might be closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.
C1 [Liu, Dong-cai] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
[Yang, Zhu-Lin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Jiang, Song] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
RP Yang, ZL (reprint author), Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, China.
EM yangzhulin8@sina.com
CR Ono R, Kobayashi S, Wagatsuma H et al, 2001, A retrotransposonderived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics 73:232–237
Okabe H, Satoh S, Furukawa Y et al, 2003, Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res 63:3043–3048
Kainz B, Shehata M, Bilban M et al, 2007, Overexpression of the paternally expressed gene 10, PEG10, from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia. Int J Cancer 121:1984–1993
Tsuji K, Yasui K, Gen Y et al, 2010, PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. Cancer Genet Cytogenet 198:118–125
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Ip WK, Lai PB, Wong NL et al, 2007, Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma. Cancer Lett 250:284–91
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Lee CT, Park KH, Yanagisawa K et al, 2004, Combination therapy with conditionally replicating adenovirus and replication defective adenovirus. Cancer Res 64:6660–6665
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 859
EP 866
DI 10.1007/s12253-011-9394-7
PG 8
ER
PT J
AU Ruppenthal, DR
Nicolini, C
Filho, FFA
Meurer, R
Damin, PA
Rohe, A
Alexandre, OPC
Damin, CD
AF Ruppenthal, D Rubia
Nicolini, Carmela
Filho, Fabiano Ferreira Antonio
Meurer, Rosalva
Damin, P Andrea
Rohe, Adriana
Alexandre, O P Claudio
Damin, C Daniel
TI TWIST1 Promoter Methylation in Primary Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; TWIST1; Methylation; Prognosis; Colon
ID Colorectal cancer; TWIST1; Methylation; Prognosis; Colon
AB TWIST1 gene, a transcription factor that belongs to the family of basic helix–loop–helix proteins, has been related to tumor progression and metastasis in different cancers. The aim of our study was to investigate TWIST1 promoter methylation in patients with primary colorectal carcinoma and determine its correlation with prognostic factors and disease outcome. Seventy-three patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as a control group. All tissues were analyzed through methylation-specific PCR. TWIST1 hypermethylation was detected in colorectal specimens of 46 patients with cancer, but in none of the tissues from the nonmalignant control group (p<0.001). In cancer patients, TWIST1 hypermethylation was found in 38 of 73 tumor samples as compared with 20 of 73 matched samples of non-cancerous colorectal tissue (P=0.001). TWIST1 hypermethylation was not correlated with prognostic predictors for the disease outcome, patients’ overall survival and disease-free survival rates. We concluded that TWIST1 hypermethylation is present in the colon and rectum of most patients with colorectal carcinoma, suggesting this molecular alteration may be involved in the process of colorectal carcinogenesis.
C1 [Ruppenthal, D Rubia] Methodist University Center (IPA), Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Nicolini, Carmela] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Filho, Fabiano Ferreira Antonio] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Meurer, Rosalva] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Damin, P Andrea] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Rohe, Adriana] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Alexandre, O P Claudio] Federal University of Health Sciences of Porto Alegre, Laboratory of Molecular BiologyPorto Alegre, RS, Brazil.
[Damin, C Daniel] Federal University of Rio Grande do Sul, Department of Surgery, Rua Ramiro Barcelos 2350, 035-903 Porto Alegre, RS, Brazil.
RP Damin, CD (reprint author), Federal University of Rio Grande do Sul, Department of Surgery, 035-903 Porto Alegre, Brazil.
EM damin@terra.com.br
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Gort EH, Suijkerbuijk KP, Roothaan SM et al, 2008, Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer. Cancer Epidemiol Biomarkers Prev 17:3325–3330
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Mironchik Y, Winnard PT Jr, Vesuna F et al, 2005, TWIST1 overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer. Cancer Res 65:10801–10809
Elias MC, Tozer KR, Silber JR et al, 2005, TWIST1 is expressed in human gliomas and promotes invasion. Neoplasia 7:824–837
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Martin TA, Goyal A, Watkins G, Jiang WG, 2005, Expression of the transcription factors snail, slug, and TWIST1 and their clinical significance in human breast cancer. Ann Surg Oncol 12:488–496
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 867
EP 872
DI 10.1007/s12253-011-9395-6
PG 6
ER
PT J
AU Cai, Ch
Jiang, Fn
Liang, Yx
He, Hch
Han, Zd
Dai, Qsh
Qin, Gq
Chen, Jh
Chen, Xb
Chen, Yr
Zeng, Gh
Zhu, Jg
Zhong, Wd
AF Cai, Chao
Jiang, Fu-neng
Liang, Yu-xiang
He, Hui-chan
Han, Zhao-dong
Dai, Qi-shan
Qin, Guo-qiang
Chen, Jia-hong
Chen, Xi-bin
Chen, Yan-ru
Zeng, Guo-hua
Zhu, Jian-guo
Zhong, Wei-de
TI Classical and Alternative Nuclear Factor-κB Pathways: A Comparison among Normal Prostate, Benign Prostate Hyperplasia and Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Nuclear factor κB; Prognosis; Prostate cancer; Real-time quantitative RT-PCR
ID Immunohistochemistry; Nuclear factor κB; Prognosis; Prostate cancer; Real-time quantitative RT-PCR
AB Nuclear factor-κB (NF-κB) is controlled by the classical and alternative NF-κB pathways, the role of which in prostate cancer (PCa) is not clearly defined. To provide this missing translational link, we compared the classical and alternative NF-κB pathways in normal prostate, benign prostate hyperplasia (BPH) and PCa. Prostate specimens were divided into three groups: group A, PCa (n=68); group B, BPH (n=60); and group C, normal prostates (n=15). The gene expression levels of NF-κB1 and NF-κB2 were determined by real-time quantitative RT-PCR. Additionally, we analyzed the expression and sub-cellular localization of phosphorylated P50 (p-P50) and phosphorylated P52 (p-P52) proteins by immunohistochemical staining. Furthermore, associations were made between NF-κB pathway proteins and patients’ prognosis. Compared with BPH and normal prostate tissues, the expression of NF-κB1 gene was differentially down-regulated by >1.5-fold, whereas NF-κB2 gene was differentially up-regulated by >2-fold in PCa tissues. The proportion of p-P50 positive patients in group A (26.5%) was significantly lower than in group B (88.3%, p=0.005) and C (100%, p=0.002). The proportion of p-P52 positive patients in group A (42.6%) was significantly higher than in group B (11.7%, p=0.009) and C (6.7%, p=0.008). Comparison of the survival curves in group A according to p-P52 expression showed a significant difference between positive and negative patients. The p-P52 positive patients showed worse prognosis (p=0.019). Our findings suggest for the first time that the classical and alternative NF-κB pathways have an important role in PCa. p-P52 might be a predictor of poor prognosis for PCa.
C1 [Cai, Chao] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Jiang, Fu-neng] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Liang, Yu-xiang] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[He, Hui-chan] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Han, Zhao-dong] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Dai, Qi-shan] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Qin, Guo-qiang] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Jia-hong] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Xi-bin] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Yan-ru] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Zeng, Guo-hua] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510230 Guangzhou, China.
[Zhu, Jian-guo] Guizhou Provincial People’s Hospital, Department of Urology, 550002 Guizhou, China.
[Zhong, Wei-de] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
RP Zhong, Wd (reprint author), Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
EM zhongwd2009@live.cn
CR Hughes C, Murphy A, Martin C et al, 2005, Molecular pathology of PCA. J Clin Path 58:673–684
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 873
EP 878
DI 10.1007/s12253-011-9396-5
PG 6
ER
PT J
AU Rouissi, K
Ouerhani, S
Hamrita, B
Bougatef, K
Marrakchi, R
Cherif, M
Ben Slama, RM
Bouzouita, M
Chebil, M
Ben Ammar Elgaaied, A
AF Rouissi, Kamel
Ouerhani, Slah
Hamrita, Bechr
Bougatef, Karim
Marrakchi, Raja
Cherif, Mohamed
Ben Slama, Riadh Mohamed
Bouzouita, Mohamed
Chebil, Mohamed
Ben Ammar Elgaaied, Amel
TI Smoking and Polymorphisms in Xenobiotic Metabolism and DNA Repair Genes are Additive Risk Factors Affecting Bladder Cancer in Northern Tunisia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Xenobiotics; DNA repair; Predisposition
ID Bladder cancer; Xenobiotics; DNA repair; Predisposition
AB Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking and genetic polymorphisms on the occurrence of bladder cancer. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of Nacetyltransferases (NAT) and glutathione S-transferases (GST). DNA repair is essential to an individual’s ability to respond to damage caused by tobacco carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to this environmental exposure. Polymorphisms in NAT2, GST and DNA repair genes alter the ability of these enzymes to metabolize carcinogens or to repair alterations caused by this process. We have conducted a case-control study to assess the role of smoking, slow NAT2 variants, GSTM1 and GSTT1 null, and XPC, XPD, XPG nucleotide excision-repair (NER) genotypes in bladder cancer development in North Tunisia. Taken alone, each gene unless NAT2 did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR=7.14; 95% CI: 1.30–51.41). However, in tobacco consumers, we have shown that Null GSTM1, Wild GSTT1, Slow NAT2, XPC (CC) and XPG (CC) are genetic risk factors for the disease. When combined together in susceptible individuals compared to protected individuals these risk factors give an elevated OR (OR=61). So, we have shown a strong cumulative effect of tobacco and different combinations of studied genetic risk factors which lead to a great susceptibility to bladder cancer.
C1 [Rouissi, Kamel] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 2092 Tunis, Tunisia.
[Ouerhani, Slah] University of Tunis El Manar, Pasteur Institute of Tunis, Laboratory of Molecular and Cellular HaematologyTunis, Tunisia.
[Hamrita, Bechr] Charles Nicole Hospital, Department of UrologyTunis, Tunisia.
[Bougatef, Karim] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 2092 Tunis, Tunisia.
[Marrakchi, Raja] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 2092 Tunis, Tunisia.
[Cherif, Mohamed] Charles Nicole Hospital, Department of UrologyTunis, Tunisia.
[Ben Slama, Riadh Mohamed] Charles Nicole Hospital, Department of UrologyTunis, Tunisia.
[Bouzouita, Mohamed] Charles Nicole Hospital, Department of UrologyTunis, Tunisia.
[Chebil, Mohamed] Charles Nicole Hospital, Department of UrologyTunis, Tunisia.
[Ben Ammar Elgaaied, Amel] University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 2092 Tunis, Tunisia.
RP Rouissi, K (reprint author), University of El Tunis Manar I, Faculty of Sciences of Tunis, Laboratory of Genetics, Immunology and Human Pathology, 2092 Tunis, Tunisia.
EM rouissik2000@yahoo.fr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 879
EP 886
DI 10.1007/s12253-011-9398-3
PG 8
ER
PT J
AU Bojkova, B
Garajova, M
Pec, M
Kubatka, P
Kajo, K
Mokan, M
Kassayova, M
Orendas, P
Kiskova, T
Ahlersova, E
Ahlers, I
AF Bojkova, Bianka
Garajova, Miroslava
Pec, Martin
Kubatka, Peter
Kajo, Karol
Mokan, Marian
Kassayova, Monika
Orendas, Peter
Kiskova, Terezia
Ahlersova, Eva
Ahlers, Ivan
TI Metabolic Effects of Pioglitazone in Chemically-Induced Mammary Carcinogenesis in Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemoprevention; Mammary carcinogenesis; Metabolism; Pioglitazone; Rat
ID Chemoprevention; Mammary carcinogenesis; Metabolism; Pioglitazone; Rat
AB In this paper, the effect of peroral antidiabetic pioglitazone, a thiazolidinedione derivate, on selected parameters of carbohydrate and lipid metabolism in Nmethyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague–Dawley rats was evaluated. Pioglitazone was administered in the diet at two concentrations (10 ppm and 100 ppm), the chemoprevention was initiated 12 days before carcinogenesis induction and lasted until the termination of the experiment. The experiment was terminated 17 weeks after carcinogenesis induction, selected organs and tissues were removed and weighed and basic metabolic and hormonal parameters were determined. Pioglitazone increased glycemia (without exceeding normal values) and glycogen concentration in both liver and heart muscle without altering insulinemia and increased triacylglycerol concentration in liver, these changes were more prominent in group with higher dose. Pioglitazone also reduced corticosterone serum concentration and attenuated lipid peroxidation. Pioglitazone and other glitazones may be useful in alleviation of unfavourable metabolic changes in cancer patients.
C1 [Bojkova, Bianka] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Garajova, Miroslava] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Pec, Martin] Comenius University, Jessenius Faculty of Medicine, Department of Medical Biology, Mala Hora 4, 037 54 Martin, Slovakia.
[Kubatka, Peter] Comenius University, Jessenius Faculty of Medicine, Department of Medical Biology, Mala Hora 4, 037 54 Martin, Slovakia.
[Kajo, Karol] Comenius University, Jessenius Faculty of Medicine, Department of Pathology, Kollarova 2, 036 01 Martin, Slovakia.
[Mokan, Marian] Comenius University, Jessenius Faculty of Medicine, Clinic of Internal Medicine I., Kollarova 2, 036 01 Martin, Slovakia.
[Kassayova, Monika] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Orendas, Peter] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Kiskova, Terezia] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Ahlersova, Eva] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
[Ahlers, Ivan] P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, Moyzesova 11, 041 67 Kosice, Slovakia.
RP Bojkova, B (reprint author), P.J.Safarik University, Faculty of Science, Institute of Biology and Ecology, 041 67 Kosice, Slovakia.
EM bianka.bojkova@upjs.sk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 887
EP 892
DI 10.1007/s12253-011-9399-2
PG 6
ER
PT J
AU Kravchick, S
Peled, R
Cytron, Sh
AF Kravchick, Sergey
Peled, Ronit
Cytron, Shmuel
TI Watchful Waiting and Active Surveillance Approach in Patients with Low Risk Localized Prostatic Cancer: An Experience of Out-Patients Clinic with 12-Year Follow-Up
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate; Cancer; Expectant management; Body mass index; TRUS-biopsy
ID Prostate; Cancer; Expectant management; Body mass index; TRUS-biopsy
AB In this study we evaluated the safety of expectant approach in the patients with low risk prostate cancer in the reality of community based out-patients clinics. 48 men were enrolled into the study. The inclusion criteria were age ranged from 60 to 75 years and the Epstein criteria for low risk prostate cancer. Patients were managed expectantly while curative treatment was offered when indicated. Initial and final Charlson comorbidity index (CCI) and BMI were assessed for all men. Patients’ median follow-up was 81.1±29.1 years. During this study 41.7% of the patients chose active forms of treatment. Cancer was found in 20.8% (n-10) of our patients. Two first sessions of re-biopsy diagnosed 92% of T1c upgrading. Six men with CCI ≥2 died from concomitant disease and no one died from PCa. Significant correlation was found between BMI and final CCI ≥2 (p-0.001). Expectant approach can be considered as self alternative to active treatment model in selected group of patients with well differentiated PCa, however 20.8% of these patients are still at risk of having aggressive form of cancer. Expectant approach is particular beneficial for the patients with CCI 1–2 and high BMI.
C1 [Kravchick, Sergey] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Peled, Ronit] Ben-Gurion University of the Negev, Faculty of Health Sciences, Department of Health Systems ManagementBeer-Sheva, Israel.
[Cytron, Shmuel] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
RP Kravchick, S (reprint author), Barzialy Medical Center, Urology Department, Ashkelon, Israel.
EM cambell@netvision.net.il;sergeyk@barzi.health.gov.il
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Djavan B, Waldert M, Zlotta A, Dobronski P, Seitz C, Remzi M, Borkowski A, Schulman C, 2001, Marberger M Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol 166(3):856–860
Post PN, Kil PJ, Hendrikx AJ, Janssen-Heijnen ML, Crommelin MA, Coebergh JW, 1999, Comorbidity in patients with prostate cancer and its relevance to treatment choice. BJU Int 84(6):652–656
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 893
EP 897
DI 10.1007/s12253-011-9400-0
PG 5
ER
PT J
AU Faccion, SR
Ferreira, MR
Grabois, FM
Fonseca, CTh
de Oliveira, AJ
Maia, CR
AF Faccion, Soares Roberta
Ferreira, Moreira Regina
Grabois, Fornaciari Marilia
Fonseca, Carvalho Theresinha
de Oliveira, Antonio Jose
Maia, Ciuvalschi Raquel
TI Lack of Prognostic Significance of Survivin in Pediatric Medulloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Survivin; Childhood; Medulloblastoma; Prognostic factor; Immunohistochemistry
ID Survivin; Childhood; Medulloblastoma; Prognostic factor; Immunohistochemistry
AB Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children. Because of the significant rate of mortality and treatment-related morbidity, the identification of prognostic factors could lead to a more accurate selection of patients who can benefit from a less aggressive therapy and improve risk stratification. Survivin is an inhibitor of apoptosis protein (IAP), the expression of which has been associated with worse prognosis in MDB. However, both of its subcellular localizations may contribute to tumor progression, and ultimately, survivin subcellular localization prognostic value depends on tumor type biological features. The goal of this study was to analyze these survivin features in the pediatric MDB tumor samples and its impact on clinical outcome. Survivin expression and subcellular localization were accessed by immunohistochemistry in a series of 41 tumor samples. Kaplan-Meier survival curves were compared using the log-rank test. Survivin expression ranged from completely absent to fully present in a notably higher pattern of nuclear localization than cytoplasmic (19 of 41 versus 4 of 41, respectively).However, survivin expression and subcellular localization were not associated with five-year overall survival or metastasis status at diagnosis, which was the only statistically significant prognostic factor in our series (p=0.008). Taken together, our results suggest that survivin expression should be further studied in large, multicenter series to determine its accurate impact on prognosis and pathobiology of pediatric MDB.
C1 [Faccion, Soares Roberta] Instituto Nacional de Cancer (INCA), Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenacao Geral Tecnico-Cientifica, Praca da Cruz Vermelha, 23, 6o andar, Ala B, Centro, 20230–130 Rio de Janeiro, RJ, Brazil.
[Ferreira, Moreira Regina] INCA, HCI, Coordenacao Geral de Gestao Assistencial, Servico de Pediatria, 20230-130 Rio de Janeiro, RJ, Brazil.
[Grabois, Fornaciari Marilia] INCA, HCI, Coordenacao Geral de Gestao Assistencial, Servico de Pediatria, 20230-130 Rio de Janeiro, RJ, Brazil.
[Fonseca, Carvalho Theresinha] Instituto Nacional de Cancer, Divisao de Patologia, 20220-400 Rio de Janeiro, RJ, Brazil.
[de Oliveira, Antonio Jose] INCA, HCI, Coordenacao Geral de Gestao Assistencial, Servico de Neurocirurgia, 20230-130 Rio de Janeiro, RJ, Brazil.
[Maia, Ciuvalschi Raquel] Instituto Nacional de Cancer (INCA), Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenacao Geral Tecnico-Cientifica, Praca da Cruz Vermelha, 23, 6o andar, Ala B, Centro, 20230–130 Rio de Janeiro, RJ, Brazil.
RP Maia, CR (reprint author), Instituto Nacional de Cancer (INCA), Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenacao Geral Tecnico-Cientifica, 20230–130 Rio de Janeiro, Brazil.
EM rcmaia@inca.gov.br
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 899
EP 908
DI 10.1007/s12253-011-9401-z
PG 10
ER
PT J
AU Li, L
Wang, YY
Zhao, ZSh
Ma, J
AF Li, Li
Wang, Yuan-Yu
Zhao, Zhong-Sheng
Ma, Jie
TI Ezrin is Associated with Gastric Cancer Progression and Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric carcinoma; Ezrin; Progression; Prognosis
ID Gastric carcinoma; Ezrin; Progression; Prognosis
AB To investigat the clinical significance of Ezrin in the development and progression of gastric cancer. Immunohistochemistry was employed to analyze Ezrin expression in 436 clinicopathologically characterized gastric cancer cases. Ezrin protein levels were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. Positive expression of Ezrin correlated with age, size of tumor, location of tumor, depth of invasion, vessel invasion, lymph node and distant metastasis and TNM stage. In stages I, II and III, the 5 year survival rate of patients with a high expression of Ezrin was significantly lower than those in patients with low expression. In stage IV, Ezrin expression did not correlate with the 5 year survival rate. Further multivariate analysis suggested that the depth of invasion, lymph node and distant metastasis, TNM stage, and up-regulation of Ezrin were independent prognostic indicators for the disease. Expression of Ezrin in gastric cancer is significantly associated with lymph node and distant metastasis, and poor prognosis. Ezrin protein could be useful markers to predict tumor progression and prognosis.
C1 [Li, Li] Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
[Wang, Yuan-Yu] Zhejiang Provincial People’s Hospital, Gastrointestinal Surgery, 310014 Hangzhou, China.
[Zhao, Zhong-Sheng] Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
[Ma, Jie] Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
RP Zhao, ZSh (reprint author), Zhejiang Provincial People’s Hospital, Department of Pathology, 310014 Hangzhou, China.
EM zhaozhongsheng50@126.com
CR Zhan W-H, Han F-H, 2008, Surgical therapy of gastric cancer in china. J Pract Oncol 23:91–93
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Meng Y, Lu Z, Yu S, Zhang Q, Ma Y, Chen J, 2010, Ezrin promotes invasion and metastasis of pancreatic cancer cells. J Transl Med 8:61
Chuan YC, Iglesias-Gato D, Fernandez-Perez L, Cedazo-Minguez A, Pang ST, Norstedt G, Pousette A, Flores-Morales A, 2010, Ezrin mediates c-Myc actions in prostate cancer cell invasion. Oncogene 29(10):1531–1542
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 909
EP 915
DI 10.1007/s12253-011-9402-y
PG 7
ER
PT J
AU Cerne, JZ
Frkovic-Grazio, S
Gersak, K
AF Cerne, Jasmina-Ziva
Frkovic-Grazio, Snjezana
Gersak, Ksenija
TI Breast Tumor Characteristics in Hormone Replacement Therapy Users
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Breast tumor characteristics; HRT use; Mammography
ID Breast cancer; Breast tumor characteristics; HRT use; Mammography
AB The aim of this study was to further elucidate the influence of HRT use, regarding duration, regimen and route of administration, on breast tumor characteristics. We evaluated the associations between HRT use and breast tumor characteristics in 530 postmenopausal women diagnosed with invasive breast cancer. Detailed information on HRT use and mammographic attendance were collected through a postal questionnaire. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression. Tumors in HRT users were significantly smaller, more often of ductal histologic type and with lower grade and lower mitotic index compared to tumors in nonusers. Tumor characteristics did not vary significantly by HRT duration, regimen and route of administration, except for mitotic index, which was more often of score 2 in long-term users, and of score 3 in short-term users. Higher mammographic surveillance among HRT users did not explain our results. We conclude that tumors in HRT users have a more favorable prognostic profile regardless of duration, regimen and route of administration. These effects seem to be due to the influence of HRT on preexisting tumors causing their greater differentiation rather than earlier detection due to mammographic surveillance.
C1 [Cerne, Jasmina-Ziva] University Medical Centre Ljubljana, Department of Obstetrics and Gynecology, Slajmerjeva 3, 1000 Ljubljana, Slovenia.
[Frkovic-Grazio, Snjezana] Institute of Oncology, Department of Pathology, Zaloska 2, 1000 Ljubljana, Slovenia.
[Gersak, Ksenija] University Medical Centre Ljubljana, Department of Obstetrics and Gynecology, Slajmerjeva 3, 1000 Ljubljana, Slovenia.
RP Gersak, K (reprint author), University Medical Centre Ljubljana, Department of Obstetrics and Gynecology, 1000 Ljubljana, Slovenia.
EM ksenija.gersak@mf.uni-lj.si
CR Rossouw JE, Anderson GL, Prentice RL et al, 2002, Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333
Collaborative Group on Hormonal Factors in Breast Cancer, 1997, Breast cancer, hormone replacement therapy: collaborative reanalysis of data from 51 epidemiology studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet 350:1047–1059
Pines A, Sturdee DW, Birkhauser MH et al, 2007, IMS updated recommendations on postmenopausal hormone therapy. Climacteric 10:181–194
Chlebowski RT, Hendrix SL, Langer RD et al, 2003, Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 289:3243–3253
Flesch-Janys D, Slanger T, Mutschelknauss E et al, 2008, Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy. Int J Cancer 123:933–941
Reeves GK, Beral V, Green J et al, 2006, Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7:910–918
Biglia N, Sgro L, Defabiani E et al, 2005, The influence of hormone replacement therapy on the pathology of breast cancer. Eur J Surg Oncol 31:467–472
Bonnier P, Bessenay F, Sasco AJ et al, 1998, Impact of menopausal hormone replacement therapy on clinical and laboratory characteristics of breast cancer. Int J Cancer 79:278–282
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Stahlberg C, Pedersen A, Andersen Z et al, 2004, Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy. Br J Cancer 91:644– 650
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Speroff L, 2008, Postmenopausal hormone therapy and the risk of breast cancer: a contrary thought. Menopause 15:393–400
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 917
EP 923
DI 10.1007/s12253-011-9403-x
PG 7
ER
PT J
AU Varga, T
Somogyi, A
Barna, G
Wichmann, B
Nagy, G
Racz, K
Selmeci, L
Firneisz, G
AF Varga, Timea
Somogyi, Aniko
Barna, Gabor
Wichmann, Barna
Nagy, Geza
Racz, Karoly
Selmeci, Laszlo
Firneisz, Gabor
TI Higher Serum DPP-4 Enzyme Activity and Decreased Lymphocyte CD26 Expression in Type 1 Diabetes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dipeptidyl peptidase-4 (DPP-4); CD26; Type 1 diabetes (T1DM); Islet cell antibody (ICA); Glutamic acid decarboxylase antibody (GAD)
ID Dipeptidyl peptidase-4 (DPP-4); CD26; Type 1 diabetes (T1DM); Islet cell antibody (ICA); Glutamic acid decarboxylase antibody (GAD)
AB Dipeptidyl peptidase-4 (DPP-4) is involved in the metabolism of peptide hormones, T-cell activation and proliferation. In type 1 diabetes mellitus (T1DM) β-cell destruction involves a number of dysregulated T-cells. Our aim was to assess the serum DPP-4 activity and the lymphocyte membrane bound CD26 expression in patients with type 1 diabetes and healthy controls. Ninety-eight (T1DM: 48, F/M=20/28, mean age: 34.4y; control: 50, F/M=39/11 mean age: 32,4y) individuals were included. Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. ICA and GAD antibodies were assessed in the T1DM group. DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flowcytometric analysis. We found higher serum DPP-4 activity (Mean: T1DM: 30.069 U/L, control: 22.62 U/L, p<0.0001) and decreased CD26 lymphocyte expression on all lymphocyte subpopulations in T1DM. Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. Here we first present that the serum DPP-4 activity is increased and the lymphocyte membrane bound CD26 expression is decreased in type 1 diabetes. Decreased lymphocyte membrane bound CD26 expression in T1DM might be a novel part of the T-lymphocyte regulatory dysfunction observed in type 1 diabetes mellitus. These results might provide some basis for the clinical implication of DPP-4 inhibition in patients with T1DM.
C1 [Varga, Timea] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Somogyi, Aniko] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Wichmann, Barna] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Nagy, Geza] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Racz, Karoly] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Selmeci, Laszlo] Semmelweis University, Department of Cardiovascular SurgeryBudapest, Hungary.
[Firneisz, Gabor] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
RP Varga, T (reprint author), Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary.
EM timcsus@yahoo.com
CR Gorrell MD, Gysbers V, McCaughan GW, 2001, CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 54:249–264
Morimoto C, Schlossman SF, 1998, The structure and function of CD26 in the T-cell immune response. Immunol Rev 161:55–70
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 925
EP 930
DI 10.1007/s12253-011-9404-9
PG 6
ER
PT J
AU Xiong, X
Ren, HZ
Li, MH
Mei, JH
Wen, JF
Zheng, ChL
AF Xiong, Xin
Ren, Hong-Zheng
Li, Min-Hua
Mei, Jin-Hong
Wen, Ji-Fang
Zheng, Chang-Li
TI Down-Regulated miRNA-214 Induces a Cell Cycle G1 Arrest in Gastric Cancer Cells by Up-Regulating the PTEN Protein
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Cell cycle; Gastric cancer cell line; miRNA-214; PTEN
ID Apoptosis; Cell cycle; Gastric cancer cell line; miRNA-214; PTEN
AB To detect the expression of miRNA-214 in human gastric cancer cell lines of BGC823, MKN45 and SGC7901, and to identify the effect of miRNA-214 on cell cycle and apoptosis of these cells. Expression of miRNA-214 in human normal gastric mucosal cell line GES-1 and human gastric cancer cell lines was detected by real-time reversetranscription polymerase chain reaction. Antisense-miRNA-214 oligonucleotides were transfected transiently into gastric cancer cell lines to down-regulate the expression of miRNA-214. The cell cycle and apoptosis were studied by flow cytometry assay. PTEN, one of the target genes of miRNA-214 was detected by using of immunocytochemistry and Western blotting. MiRNA-214 was overexpressed in gastric cancer cell lines of BGC823, MKN45 and SGC7901 compared with normal gastric mucosal cell line GES-1. Antisense-miRNA-214 oligonucleotides significantly down-regulated the expression of miRNA-214, and increased the portion of G1-phase and decreased the portion of S-phase in BGC823 and MKN45 cells. The immunocytochemistry test and Western blotting analysis showed that the down-regulation of miRNA-214 could significantly up-regulate the expression of PTEN in BGC823 and MKN45 cells. MiRNA-214 is overexpressed in human gastric cancer cell lines of BGC823, MKN45 and SGC7901. The down-regulation of miRNA-214 could induce a G1 cell cycle arrest in them, the up-regulation of PTEN maybe one of the mechanism.
C1 [Xiong, Xin] Central South University, Xiangya Basic Medical College, Department of Pathology, 410013 Changsha, Hunan Province, China.
[Ren, Hong-Zheng] Central South University, Xiangya Basic Medical College, Department of Pathology, 410013 Changsha, Hunan Province, China.
[Li, Min-Hua] the First Affiliated Hospital of Nanchang University, Department of Pathology, 330006 Nanchang, Jiangxi Province, China.
[Mei, Jin-Hong] the First Affiliated Hospital of Nanchang University, Department of Pathology, 330006 Nanchang, Jiangxi Province, China.
[Wen, Ji-Fang] Central South University, Xiangya Basic Medical College, Department of Pathology, 410013 Changsha, Hunan Province, China.
[Zheng, Chang-Li] Central South University, Xiangya Basic Medical College, Department of Pathology, 410013 Changsha, Hunan Province, China.
RP Zheng, ChL (reprint author), Central South University, Xiangya Basic Medical College, Department of Pathology, 410013 Changsha, China.
EM changlizheng1125@yahoo.com.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 931
EP 937
DI 10.1007/s12253-011-9406-7
PG 7
ER
PT J
AU Wu, Q
Yang, Z
Hu, S
Su, T
An, Y
Zhang, Z
Nie, Y
Wang, X
Shi, Y
Fan, D
AF Wu, Qiong
Yang, Zhiping
Hu, Sijun
Su, Tao
An, Yanxin
Zhang, Zhiyong
Nie, Yongzhan
Wang, Xin
Shi, Yongquan
Fan, Daiming
TI Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clinic pathologic; PTEN; P21; P57; C-Myc; Stemness; Prognosis
ID Clinic pathologic; PTEN; P21; P57; C-Myc; Stemness; Prognosis
AB Cancer stem cells are nowadays considered to be the origin of cancer. Also, stem cell associated genes are emerging as predictors of cancer malignancy. We investigated the association of several stemness genes (c-Myc, PTEN, p57 and p21) with clinic pathological parameters and survival in stomach cancer by performing immunohistochemistry on paraffin sections of gastric cancer patients who underwent surgical staging with following-up statistics. We discovered that expression of c-Myc was significantly related to distant metastasis, the combined expression of PTEN and p21 correlated positively to overall survival, while p57 was less useful in overall survival prediction in gastric cancer. Additionally, there is a positive correlation between expressions of p57 and p21. In conclusion, our present study indicated that expression of stemness genes (c-Myc, PTEN, p57 and p21) performed different predictive potential in the evaluation of clinical malignancy levels in gastric cancer.
C1 [Wu, Qiong] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Yang, Zhiping] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Hu, Sijun] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Su, Tao] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[An, Yanxin] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Zhang, Zhiyong] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Nie, Yongzhan] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Wang, Xin] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Shi, Yongquan] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
[Fan, Daiming] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 127 Changle Western Road, 710032 Xi’an, Shaanxi, China.
RP Shi, Y (reprint author), Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
EM shiyquan@fmmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 939
EP 946
DI 10.1007/s12253-011-9407-6
PG 8
ER
PT J
AU Li, D
Cui, Q
Liu, Y
Wang, X
Liu, Ch
Liu, Sh
Zeng, Y
AF Li, Dingfeng
Cui, Qiu
Liu, Yaosheng
Wang, Xiaohong
Liu, Cheng
Liu, Shubin
Zeng, Yanjun
TI Chemotherapy Response Analysis for Osteosarcom with Intra-arterial Chemotherapy by Subcutaneous Implantable Delivery System
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Neoadjuvant chemotherapy; Arterial chemotherapy; Survival rate
ID Osteosarcoma; Neoadjuvant chemotherapy; Arterial chemotherapy; Survival rate
AB To summarize the experience in intraarterial neoadjuvant chemotherapy for extremity osteosarcoma. Between January 2002 and December 2007,111 patients with stage IIB extremity osteosarcoma received preoperative intraarterial therapy with subcutaneous implantation of chemotherapy pump as well as en bloc resection, and postoperative adjuvant chemotherapy. There were 63 males and 48 females with an average age of 18 (range, 14~39 years). The time from symptom onset to hospitalization varied from several days to 6 months. The induction chemotherapy regimen includes: epirubicin [50~70 mg/m2 by 4-hour intraarterial infusion/day for 3 day] and cisplatin [100~120 mg/m2 by 2-hour intraarterial infusion/day for 3 days] repetitively every 2~3 weeks. Among which 24 cases only received two cycles induction chemotherapy was set to nonstandard chemotherapy group and 87 cases received three to six cycles induction chemotherapy set to standard chemotherapy group. The number of preoperative chemotherapy-cycles of standard chemotherapy group depends on the clinical and radiographic evaluation of chemotherapy efficacy. Median follow-up time was 28(8~48) months. The rate of limb preservation surgery was 89.53% (77/86) in standard chemotherapy group,and was 37.5% (9/24) in nonstandard chemotherapy group. Kaplan-Meier survival analysis showed that the 3-year overall survival rate and disease free survival rate of all the 111 cases were 68.3% and 65.9% respectively. There were significant differences in overall survival rate (38.9%, 80.0%, P=0.000), disease free survival rate (30.1%, 79.5%, P=0.000), distant metastasis rate (66.67%, 16.09%, P=0.0000) and local recurrence rate (58.33%, 13.79%, P=0.0000) between nonstandard chemotherapy group and standard chemotherapy group. Standard intraarterial neo-adjuvant chemotherapy was more effective than nonstandard intraarterial induction chemotherapy to stage IIB extremity osteosarcoma.
C1 [Li, Dingfeng] 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
[Cui, Qiu] 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
[Liu, Yaosheng] 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
[Wang, Xiaohong] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
[Liu, Cheng] 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
[Liu, Shubin] 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
[Zeng, Yanjun] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
RP Li, D (reprint author), 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
EM 307yygk@sina.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 947
EP 953
DI 10.1007/s12253-011-9408-5
PG 7
ER
PT J
AU Stanczak, A
Stec, R
Bodnar, L
Olszewski, W
Cichowicz, M
Kozlowski, W
Szczylik, C
Pietrucha, T
Wieczorek, M
Lamparska-Przybysz, M
AF Stanczak, Aleksandra
Stec, Rafal
Bodnar, Lubomir
Olszewski, Wojciech
Cichowicz, Marzena
Kozlowski, Wojciech
Szczylik, Cezary
Pietrucha, Tadeusz
Wieczorek, Maciej
Lamparska-Przybysz, Monika
TI Prognostic Significance of Wnt-1, β-catenin and E-cadherin Expression in Advanced Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE β-catenin; E-cadherin; Wnt-1; Wnt signaling pathway; Advanced colorectal carcinoma; Prognostic factor
ID β-catenin; E-cadherin; Wnt-1; Wnt signaling pathway; Advanced colorectal carcinoma; Prognostic factor
AB Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of Ecadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma.
C1 [Stanczak, Aleksandra] Medical University of Lodz, Department of Medical BiotechnologyLodz, Poland.
[Stec, Rafal] Military Institute of Medicine, Oncology DepartmentWarsaw, Poland.
[Bodnar, Lubomir] Military Institute of Medicine, Oncology DepartmentWarsaw, Poland.
[Olszewski, Wojciech] Medical Center for Postgraduate Education, and Maria Sk³odowska-Curie Memorial Cancer Center and Institute of Oncology, Department of PathologyWarsaw, Poland.
[Cichowicz, Marzena] Military Institute of Medicine, Pathomorphology DepartmentWarsaw, Poland.
[Kozlowski, Wojciech] Military Institute of Medicine, Pathomorphology DepartmentWarsaw, Poland.
[Szczylik, Cezary] Military Institute of Medicine, Oncology DepartmentWarsaw, Poland.
[Pietrucha, Tadeusz] Medical University of Lodz, Department of Medical BiotechnologyLodz, Poland.
[Wieczorek, Maciej] Celon Pharma Ltd, Innovative Drugs Research & Development Department, 41A Mokra St. Kielpin, 05–092 Lomianki, Poland.
[Lamparska-Przybysz, Monika] Celon Pharma Ltd, Innovative Drugs Research & Development Department, 41A Mokra St. Kielpin, 05–092 Lomianki, Poland.
RP Stanczak, A (reprint author), Medical University of Lodz, Department of Medical Biotechnology, Lodz, Poland.
EM aleksandra.stanczak@celonpharma.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 955
EP 963
DI 10.1007/s12253-011-9409-4
PG 9
ER
PT J
AU Chen, ShW
Guo, ZM
Zhang, Q
Yang, AK
Li, QL
Zhuang, ShM
Wang, LP
Song, M
AF Chen, Shu-Wei
Guo, Zhu-Ming
Zhang, Quan
Yang, An-Kui
Li, Qiu-Li
Zhuang, Shi-Min
Wang, Li-Ping
Song, Ming
TI Invasion of the Hypoglossal Nerve by Adenoid Cystic Carcinoma of the Tongue: Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Neural invasion; Adenoid cystic carcinoma; Hypoglossal nerve; Tongue; Treatment
ID Neural invasion; Adenoid cystic carcinoma; Hypoglossal nerve; Tongue; Treatment
AB Adenoid cystic carcinoma (ACC) is a rare but highly aggressive malignancy mainly originating from the salivary glands. ACC is well known for its propensity toward neural invasion (NI). NI is the process of neoplastic invasion in and along nerves. It is a distinct and welldocumented phenomenon in ACC; however, it is an underestimated route of metastatic spread. Multiple distant metastases can be established through NI route, and NI is believed to portend a poor prognosis. Despite increasing recognition of NI in many malignancies, the molecular mechanism behind NI is not well established. We present a unique case of hypoglossal nerve invasion by ACC arising from the minor salivary glands in the tongue of a 34-yearold man. We also review and discuss current theories on the pathogenesis and mechanism of NI.
C1 [Chen, Shu-Wei] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Guo, Zhu-Ming] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Zhang, Quan] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Yang, An-Kui] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Li, Qiu-Li] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Zhuang, Shi-Min] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Wang, Li-Ping] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Song, Ming] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
RP Song, M (reprint author), Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 510060 Guangzhou, China.
EM songming@sysucc.org.cn
CR Spiro RH, Huvos AG, Strong EW, 1974, Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg 128:512–520
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Barrett AW, Speight PM, 2009, Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol 45:936–940
Silvester KC, Barnes S, 1990, Adenoid cystic carcinoma of the tongue presenting as a hypoglossal nerve palsy. Br J Oral Maxillofac Surg 28:122–124
Wang D, Li Y, He H, Liu L, Wu L, He Z, 2007, Intraoral minor salivary gland tumors in a Chinese population: a retrospective study on 737 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:94–100
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Hanna E, Vural E, Prokopakis E, Carrau R, Snyderman C, Weissman J, 2007, The sensitivity and specificity of highresolution imaging in evaluating perineural spread of adenoid cystic carcinoma to the skull base. Arch Otolaryngol Head Neck Surg 133:541–545
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Beard CJ, Chen MH, Cote K, Loffredo M, Renshaw AA, Hurwitz M et al, 2004, Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer. Int J Radiat Oncol Biol Phys 58:19–24
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Ayala GE, Wheeler TM, Shine HD, Schmelz M, Frolov A, Chakraborty S et al, 2001, In vitro dorsal root ganglia and human prostate cell line interaction: redefining perineural invasion in prostate cancer. Prostate 49:213–223
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Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM et al, 2006, Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 965
EP 968
DI 10.1007/s12253-010-9339-6
PG 4
ER
PT J
AU Yu, L
Yang, JSh
AF Yu, Lu
Yang, Jing Shou
TI Kaposiform Hemangioendothelioma of the Spleen in an Adult: An Initial Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Kaposiform hemangioendothelioma; Kasabach–Merritt phenomenon; Vascular tumor; Immunohistochemistry; Spleen
ID Kaposiform hemangioendothelioma; Kasabach–Merritt phenomenon; Vascular tumor; Immunohistochemistry; Spleen
AB Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular neoplasm characterized by infiltrating nodules and sheets of spindle cells, and unmistakable resemblance to Kaposi's sarcoma. KHE occurs mainly in newborns and infants and presents most commonly in the skin, deep soft tissue, and bone. We report a case of KHE in a 36-year-old female who presented with a spleen mass and underwent splenectomy. Macroscopic examination revealed a large, dark-red, firm mass in the spleen. Histologically, the tumor consisted of irregular, infiltrating nodules of densely packed spindle-shaped tumor cells closely associated with small slit-like and sieve-like blood vessels, which were separated with hyalinized hypocellular fibrous stroma. Immunohistochemically, both spindle and epithelioid cells were positive for CD34, CD31, and vimentin, but negative for EMA, cytokeratin, CD21, CD35, CD1a, and S-100 protein. The well-formed capillaries and mature vessels but not spindle tumor cell showed reactivity for factor VIII- related antigen. Alpha-Smooth muscle actin was detected in pericytes surrounding small round or slit-like capillaries. The final histologic diagnosis was KHE. Followup 6 month after operation revealed no sign of recurrence or metastasis.To the best of our knowledge, this is the first report of KHE arising in the spleen.
C1 [Yu, Lu] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 17 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
[Yang, Jing Shou] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 17 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
RP Yang, JSh (reprint author), Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
EM yangsj@fmmu.edu.cn
CR Tsang WYW, 2002, Kaposiform hemangioendothelioma. World Health Organization Classification of Tumours: pathology and genetics of tumours of the soft tissues and bones. In: Fletcher CDM, Unni KK, Mertens F, eds). IARC, Lyon, pp 163–164
Zukerberg LR, Nickoloff BJ, Weiss SW, 1993, Kaposiform hemangioendothelioma of infancy and childhood. An aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. Am J Surg Pathol 17:321–328
Lyons LL, North PE, Mac-Moune Lai F, Stoler MH, Folpe AL, Weiss SW, 2004, Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol 28:559–568
Mac-Moune Lai F, To KF, Choi PC, Leung PC, Kumta SM, Yuen PP, Lam WY, Cheung AN, Allen PW, 2001, Kaposiform hemangioendothelioma: five patients with cutaneous lesion and long follow-up. Mod Pathol 14:1087–1092
Fernandez Y, Bernabeu-Wittel M, Garcia-Morillo JS, 2009, Kaposiform hemangioendothelioma. Eur J Intern Med 20:106–113
Mentzel T, Mazzoleni G, Dei Tos AP, Fletcher CD, 1997, Kaposiform hemangioendothelioma in adults. Clinicopathologic and immunohistochemical analysis of three cases. Am J Clin Pathol 108:450–455
San Miguel FL, Spurbeck W, Budding C, Horton J, 2008, Kaposiform hemangioendothelioma: a rare cause of spontaneous hemothorax in infancy. Review of the literature. J Pediatr Surg 43:e37–e41
Tello MA, Shields G, Gadre SA, Ryan M, 2004, Pathology quiz case 2. Diagnosis: Kaposiform hemangioendothelioma, KHE). Arch Otolaryngol Head Neck Surg 130:991, diag 993–994
Sarkar M, Mulliken JB, Kozakewich HP, Robertson RL, Burrows PE, 1997, Thrombocytopenic coagulopathy, Kasabach-Merritt phenomenon, is associated with Kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg 100:1377–1386
Blei F, Karp N, Rofsky N, Rosen R, Greco MA, 1998, Successful multimodal therapy for kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: case report and review of the literature. Pediatr Hematol Oncol 15:295–305
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 969
EP 972
DI 10.1007/s12253-010-9331-1
PG 4
ER
PT J
AU Cui, Q
Li, D
Liu, Ch
Guo, J
Liu, Sh
Liu, Y
Zhai, MJ
Zeng, Y
AF Cui, Qiu
Li, Dingfeng
Liu, Cheng
Guo, Jun
Liu, Shubin
Liu, Yaosheng
Zhai, M J
Zeng, Yanjun
TI Two Case-Reports of the Limb Salvage Treatment of Osteosarcoma Consolidated with Obvious Pathological Fractures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Osteosarcoma; Pathological fracture; Limb salvage treatment; Chemotherapy
ID Osteosarcoma; Pathological fracture; Limb salvage treatment; Chemotherapy
AB Objective: The effect of the limb salvage of the treatment of Osteosarcoma Consolidated with Obvious Pathological Fractures is not very well, the purpose of this paper is to track the efficacy of limb salvage treatment when the patients accepted the artery intervention chemotherapy and enclosed 2 clinical case-reports. Methods: From January 2003 to September 2005, 2 clinical cases which one is a male, 29 years old, was confirmed osteosarcoma on the left distal femur, and the other is a female, 15 years old and has osteosarcoma on the right arm with obvious pathological fracture. After receiving arterial chemotherapy pump embedded, then started chemotherapy after the tumor biopsy, and the next process prosthesis replacement in limb salvage surgery after 5 times chemotherapy, follow on the next 5 times chemotherapy after the surgery. Results: With an average follow-up 70 months, there are no postoperative infection and prosthesis loosening found, also didn’t detected tumor recurrence and metastasis, and the limb function recovered well. Conclusions: With the effective, neoadjuvant chemotherapy and comprehensive treatment, salvage treatment is not the contraindication of the patients with pathological fractures of combined primary osteosarcoma, and the treatment with long-term follow-up effectively.
C1 [Cui, Qiu] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Li, Dingfeng] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Liu, Cheng] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Guo, Jun] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Liu, Shubin] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Liu, Yaosheng] Academy of Military Medical Sciences, Department of Bone Tumor, No.8 of East Avenue, Fengtai District, 100071 Beijing, China.
[Zhai, M J] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
[Zeng, Yanjun] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
RP Li, D (reprint author), Academy of Military Medical Sciences, Department of Bone Tumor, 100071 Beijing, China.
EM 307yygk@sina.com
CR McKenna RJ, Schwinn CP, Soong KY et al, 1966, Sarcomata of osteogenic series: an analysis of 553 cases. J Bone Joint Surg Am 48:1–26
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2011
VL 17
IS 4
BP 973
EP 979
DI 10.1007/s12253-010-9347-6
PG 7
ER
PT J
AU Vegso, Gy
Gorog, D
Fehervari, I
Nemes, B
Doros, A
Langer, MR
Kobori, L
AF Vegso, Gyula
Gorog, Denes
Fehervari, Imre
Nemes, Balazs
Doros, Attila
Langer, Miklos Robert
Kobori, Laszlo
TI Role of Organ Transplantation in the Treatment of Malignancies – Hepatocellular Carcinoma as the Most Common Tumour Treated with Transplantation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Bridging therapy; Bronchioloalveolar carcinoma; Des-gamma-carboxy prothrombin; Extended criteria; Heart sarcomas; Hepatocellular carcinoma; Living donor liver transplantation; Liver transplantation; Milan criteria; Proliferation signal inhibitor
ID Bridging therapy; Bronchioloalveolar carcinoma; Des-gamma-carboxy prothrombin; Extended criteria; Heart sarcomas; Hepatocellular carcinoma; Living donor liver transplantation; Liver transplantation; Milan criteria; Proliferation signal inhibitor
AB There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapies may help prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The greatest experience with this procedure is in Asia. Despite the favourable results, LT as the treatment of HCC is debated and raises several questions: regarding indication and expectable outcome. Milan criteria seem to answer this questions although they are too strict. The number and size of HCC foci per se is not sufficient predictor of eligibility to transplantation and for prognosis. Majority of the prognostic factors can be evaluated only after transplantation with pathological examination of HCC. Aim of the present research is to find prognostic factors that are characteristic of biological behaviour of HCC, which can be detected before LT in order to select patients who have the greatest benefit from LT. Re-definition of eligibility criteria is an actual question; an international consensus based on additional prospective studies is required for the "new" recommendation.
C1 [Vegso, Gyula] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Gorog, Denes] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Fehervari, Imre] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Nemes, Balazs] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Doros, Attila] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Langer, Miklos Robert] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
[Kobori, Laszlo] Semmelweis University, Department of Transplantation and Surgery, Baross u. 23, 1082 Budapest, Hungary.
RP Vegso, Gy (reprint author), Semmelweis University, Department of Transplantation and Surgery, 1082 Budapest, Hungary.
EM vegso.gyula@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 1
EP 10
DI 10.1007/s12253-011-9441-4
PG 10
ER
PT J
AU Kakihana, K
Ohashi, K
Hirashima, Y
Murata, Y
Kobayashi, T
Yamashita, T
Sakamaki, H
Akiyama, H
AF Kakihana, Kazuhiko
Ohashi, Kazuteru
Hirashima, Yuka
Murata, Yutaka
Kobayashi, Takeshi
Yamashita, Takuya
Sakamaki, Hisashi
Akiyama, Hideki
TI Clinical Impact of Pre-transplant Pulmonary Impairment on Survival After Allogeneic Hematopoietic Stem Cell Transplantation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Fatal pulmonary complication; Obstructive ventilatory impairment; Restrictive ventilatory impairment; Reduced intensity conditioning regimen
ID Fatal pulmonary complication; Obstructive ventilatory impairment; Restrictive ventilatory impairment; Reduced intensity conditioning regimen
AB We retrospectively analyzed the clinical outcomes of patients with pulmonary impairment before undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for the first time. Among 297 evaluable patients who underwent their first HSCT, 23 had restrictive, obstructive or mixed ventilatory impairment (n=9, 13 and 1, respectively). Males predominated among the patients with pulmonary impairment (p=0.037) and received a reduced intensity conditioning (RIC) regimen more frequently, although the difference did not reach statistical significance (p=0.05). Among 23 patients with pulmonary impairment, 9 underwent post-transplant pulmonary function tests and obstructive ventilatory impairment progressed only in 2 patients, both of whom developed bronchiolitis obliterans. Kaplan-Meier estimates of 3-year overall (OS) among patients with and without pulmonary impairment were 57% and 47%, respectively, and those of relapse-free survival (RFS) were 70%, and 68%, respectively, with no significant differences between the groups (OS, p=0.235; RFS, p=0.287). The rates of nonrelapse mortality also did not significantly differ (p=0.835). Our results suggest that allogeneic HSCT is safe for patients with pulmonary impairment. The lower frequency of fatal pulmonary complications after HSCT and the RIC regimen might contribute to favorable survival rates.
C1 [Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Hirashima, Yuka] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center, Pharmacy DivisionTokyo, Japan.
[Murata, Yutaka] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Kobayashi, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Yamashita, Takuya] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
[Akiyama, Hideki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113–8677 Tokyo, Japan.
RP Kakihana, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113–8677 Tokyo, Japan.
EM kakihana@cick.jp
CR Marras TK, Szalai JP, Chan CK, Lipton JH, Messner HA, Laupacis A, 2002, Pulmonary function abnormalities after allogeneic marrow transplantation: a systematic review and assessment of an existing predictive instrument. Bone Marrow Transplant 30:599–607
Badier M, Guillot C, Delpierre S, Vanuxem P, Blaise D, Maraninchi D, 1993, Pulmonary function changes 100 days and one year after bone marrow transplantation. Bone Marrow Transplant 12:457–461
Gore EM, Lawton CA, Ash RC, Lipchik RJ, 1996, Pulmonary function changes in long-term survivors of bone marrow transplantation. Int J Radiat Oncol Biol Phys 36:67–75
Chiou TJ, Tung SL, Wang WS, Tzeng WF, Yen CC, Fan FS et al, 2002, Pulmonary function changes in long-term survivors of chronic myelogenous leukemia after allogeneic bone marrow transplantation: a Taiwan experience. Cancer Invest 20:880–888
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El-Khatib M, Bou-Khalil P, Abbas O, Salman A, Jamaleddine G, 2007, Value of pretransplant pulmonary function tests in predicting pulmonary complications after autologous peripheral stem cell transplantation. Lung 185:321–324
Savani BN, Montero A, Srinivasan R, Singh A, Shenoy A, Mielke S et al, 2006, Chronic GVHD and pretransplantation abnormalities in pulmonary function are the main determinants predicting worsening pulmonary function in long-term survivors after stem cell transplantation. Biol Blood Marrow Transplant 12:1261–1269
Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG et al, 2003, Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med 168:208–214
Chien JW, Madtes DK, Clark JG, 2005, Pulmonary function testing prior to hematopoietic stem cell transplantation. Bone Marrow Transplant 35:429–435
Ghalie R, Szidon JP, Thompson L, Nawas YN, Dolce A, Kaizer H, 1992, Evaluation of pulmonary complications after bone marrow transplantation: the role of pretransplant pulmonary function tests. Bone Marrow Transplant 10:359–365
Lee MY, Chiou TJ, Yang MH, Bai LY, Hsiao LT, Chao TC et al, 2005, Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation. Eur J Haematol 74:152–157
Goldberg SL, Klumpp TR, Magdalinski AJ, Mangan KF, 1998, Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients. J Clin Oncol 16:3796–3802
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al, 2005, Hematopoietic cell transplantation, HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106:2912–2919
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 11
EP 16
DI 10.1007/s12253-011-9383-x
PG 6
ER
PT J
AU Liu, X
He, Z
Li, Ch
Huang, G
Ding, C
Liu, H
AF Liu, Xingyan
He, Zhiwei
Li, Cai-hong
Huang, Guoliang
Ding, Congcong
Liu, Hong
TI Correlation Analysis of JAK-STAT Pathway Components on Prognosis of Patients with Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Janus kinases; Signal transducers and activator of transcription; Clinical pathology; Prognosis
ID Prostate cancer; Janus kinases; Signal transducers and activator of transcription; Clinical pathology; Prognosis
AB Janus kinases (JAK)/signal transducers and activator of transcription (STAT) pathway is activated constitutively in prostate cancer (PCa). Despite previous reports implying a role of this pathway in the development of clinical hormone-refractory PCa, the correlation of pathway members with the clinicopathologic features and prognosis of patients with PCa has not been elucidated. To address this problem, pJAK-1Tyr1022/1023 and pSTAT-3Tyr705 were evaluated by immunostaining in needle biopsies of the prostate from 202 PCa patients treated by definitive therapy (105 cases) or hormonal therapy (97 cases). The correlation of two protein expression with the clinicopathologic features and the prognosis of PCa were subsequently assessed. The expression levels of pJAK-1Tyr1022/1023 and pSTAT-3Tyr705 were both positively correlated with Gleason score and clinical stage of patients with PCa. Their expression was also significantly higher in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (both P<0.001). In all patients, the recurrence-free survival (RFS) rates were significantly higher in those with low pJAK-1Tyr1022/1023 and pSTAT-3Tyr705 expression than that in those with high expression (both P<0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with lower pJAK-1Tyr1022/1023 (P<0.001 and 0.012, respectively) and pSTAT-3Tyr705 expression (P<0.001 and 0.015, respectively) were significantly higher than in those with higher expression. Cox multivariate analysis showed that the expression levels of pJAK-1Tyr1022/1023 (P=0.002) and pSTAT-3Tyr705 (P=0.005) were prognostic factors for PCa in addition to extraprostatic extension (P=0.026) and Gleason score (P=0.018). The results of pJAK-1Tyr1022/1023 and pSTAT-3Tyr705 immunostainings in needle-biopsy specimens are prognostic factors for PCa.
C1 [Liu, Xingyan] Guangdong Medical University, Cancer Research Institute, 523808 Dongguan, Guangdong, China.
[He, Zhiwei] Guangdong Medical University, Cancer Research Institute, 523808 Dongguan, Guangdong, China.
[Li, Cai-hong] Key Laboratory of Medical Molecular Activity Research, 523808 Dongguan, Guangdong, China.
[Huang, Guoliang] Guangdong Medical University, Cancer Research Institute, 523808 Dongguan, Guangdong, China.
[Ding, Congcong] Guangdong Medical University, Cancer Research Institute, 523808 Dongguan, Guangdong, China.
[Liu, Hong] Guangdong Medical University, 523808 Dongguan, Guangdong, China.
RP Liu, H (reprint author), Guangdong Medical University, 523808 Dongguan, China.
EM alison0428@126.com
CR Kehinde EO, Maghrebi MA, Anim JT, 2008, The importance of determining the aggressiveness of prostate cancer using serum and tissue molecular markers. Can J Urol 15:3967–74
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 17
EP 23
DI 10.1007/s12253-011-9410-y
PG 7
ER
PT J
AU Kacar, A
Arikok, TA
Kokenek Unal, DT
Onder, E
Hucumenoglu, S
Alper, M
AF Kacar, Ayper
Arikok, Turker Ata
Kokenek Unal, Dilay Tuba
Onder, Evrim
Hucumenoglu, Sema
Alper, Murat
TI Stromal Expression of CD34, α-Smooth Muscle Actin and CD26/DPPIV in Squamous Cell Carcinoma of the Skin: A Comparative Immunohistochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD34; α-SMA; CD26; Squamous cell carcinoma; Tumor stroma
ID CD34; α-SMA; CD26; Squamous cell carcinoma; Tumor stroma
AB Invasion pathogenesis is one of the most complicated issues in the literature. There are numerous studies concerning the tumor markers implicated in the preinvasiveinvasive tumor sequence. Despite ample studies on the invasion pathogenesis of cutaneous melanomas, there is limited and dispersed work presently available on nonmelanoma skin cancer. The vast knowledge in the literature concerning this issue in squamous cell carcinoma comes mostly from the studies of the oral cavity, esophagus, larynx, and cervix. In this study, we investigated tumor-free neighboring stroma and tumor stroma in squamous cell carcinomas (SCCs) of the skin as well as keratoacanthomas (KAs) with respect to the presence of stromal CD34-positive (CD34+) fibrocytes and α-smooth muscle actin-positive (α-SMA+) myofibroblasts using seborrheic keratosis (SKs) and nontumoral skin samples as controls. We also evaluated the stromal expression pattern of CD26/DPPIV (CD26), a tumor suppressor gene product that also has immunoregulatory properties. Immunohistochemistry was performed on samples of 31 SCC, 8 KA, 15 SK and 10 non-tumoral skin samples. Peri-tumoral stroma from resection margins was also evaluated. We found that CD34 and α-SMA demonstrated significantly different staining between benign and malignant squamous skin lesions consisting of a loss of CD34+ fibrocytes paralleled by a gain of α-SMA+ myofibroblasts in malignant tumor stroma. Additionally, it was shown that CD26 expression was lower in tumor stroma when compared to that of tumor neighboring stroma. However, we concluded that this finding may be attributable to the solar elastosis areas in the peritumoral tissue, which shows diffuse strong positivity for this marker.
C1 [Kacar, Ayper] Ankara Children’s Hematology and Oncology Hospital, Pathology DepartmentAnkara, Turkey.
[Arikok, Turker Ata] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Kokenek Unal, Dilay Tuba] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Onder, Evrim] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Hucumenoglu, Sema] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Pathology DivisionAnkara, Turkey.
[Alper, Murat] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
RP Kacar, A (reprint author), Ankara Children’s Hematology and Oncology Hospital, Pathology Department, Ankara, Turkey.
EM ayperkacar@yahoo.com
CR Kojc N, Zidar N, Vodopivec B et al, 2005, Expression of CD 34, alpha-smooth muscle actin, and transforming growth factor beta-1 in squamous intraepithelial lesions and squamous cell carcinoma of larynx and hypopharynx. Hum Pathol 36(1):16–21
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Barth PJ, Zu Schweinsberg TS, Ramaswamy A, Moll R, 2004, CD 34 + fibrocytes, alpha-smooth muscle antigen-positive myofibroblasts, and CD 117 expression in the stroma of invasive squamous cell carcinomas of the oral cavity pharynx and larynx. Virchows Arch 444(3):231–234
Barth PJ, Ebrahimsade S, Hellinger A et al, 2002, CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions. Virchows Arch 440:128–133
Barth PJ, Ebrahimsade S, Ramaswamy A et al, 2002, CD34+ fibrocytes in invasive ductal carcinoma, ductal carcinoma in situ, and benign lesions. Virchows Arch 440:298–303
Barth PJ, Ramaswamy A, Moll R et al, 2002, CD34+ fibrocytes in normal cervical stroma, cervical intraepithelial neoplasia III, and invasive squamous cell carcinoma of the cervix uteri. Virchows Arch 441:564–568
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Thielitz A, Vetter RW, Schultze B et al, 2008, Inhibitors of dipeptidyl peptidase IV-like activity mediate antifibrotic effects in normal and keloid derived skin fibroblasts. J Invest Dermatol 128, 4):855–866
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Campbell TB, Hangoc G, Liu Yet al, 2007, Inhibition of CD26 in human cord blood CD34+ cells enhances their engraftment of nonobese diabetic/severe combined immunodeficiency mice. Stem Cells Dev 16(3):347–354
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 25
EP 31
DI 10.1007/s12253-011-9412-9
PG 7
ER
PT J
AU Kafousi, M
Vrekoussis, Th
Tsentelierou, E
Pavlakis, K
Navrozoglou, I
Dousias, V
Sanidas, E
Tsiftsis, D
Georgoulias, V
Stathopoulos, NE
AF Kafousi, Maria
Vrekoussis, Thomas
Tsentelierou, Eleftheria
Pavlakis, Kitty
Navrozoglou, Iordanis
Dousias, Vassilios
Sanidas, Elias
Tsiftsis, Dimitrios
Georgoulias, Vassilios
Stathopoulos, N Efstathios
TI Immunohistochemical Study of the Angiogenetic Network of VEGF, HIF1α, VEGFR-2 and Endothelial Nitric Oxide Synthase (eNOS) in Human Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiogenesis; Breast Cancer; eNOS; VEGF
ID Angiogenesis; Breast Cancer; eNOS; VEGF
AB Background: The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse. The aim of the current study was to investigate the expression of key molecules involved in these opposite pathways in primary breast cancer. Methods: Representative tumor samples from 242 patients with early-stage breast cancer (invasive ductal breast carcinomas) were investigated for the expression of VEGF, VEGFR-2, HIF1α, iNOS, and eNOS using immunohistochemistry. Results: Endothelial NOS was found in 159 cases, VEGF in 131 cases, HIF-1α in 139 cases, VEGFR2 in 185 cases and inducible NOS (iNOS) in 22 cases. There was a significant correlation between the expression of VEGF and VEGFR-2, eNOS and VEGF, eNOS and VEGFR-2, eNOS and HIF1α. No statistically significant correlation was found between iNOS and the rest of the studied molecules. Conclusions: In breast cancer cases, the major molecules regulating NO and VEGF production can be co-expressed in the individual carcinomas implying a possibility for the relevant pathways to be active; however appropriate functional experiments remain to be conducted to prove such a hypothesis.
C1 [Kafousi, Maria] Medical School of the University of Crete, Department of Pathology, Voutes, 70003 Heraklion, Crete, Greece.
[Vrekoussis, Thomas] Medical School of the University of Crete, Department of Pathology, Voutes, 70003 Heraklion, Crete, Greece.
[Tsentelierou, Eleftheria] Medical School of the University of Crete, Department of Pathology, Voutes, 70003 Heraklion, Crete, Greece.
[Pavlakis, Kitty] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Navrozoglou, Iordanis] Ioannina University Hospital, Department of Obstetrics and GynecologyIoannina, Epirus, Greece.
[Dousias, Vassilios] Ioannina University Hospital, Department of Obstetrics and GynecologyIoannina, Epirus, Greece.
[Sanidas, Elias] Medical School, University of Crete, Department of Surgical OncologyHeraklion, Crete, Greece.
[Tsiftsis, Dimitrios] Medical School, University of Crete, Department of Surgical OncologyHeraklion, Crete, Greece.
[Georgoulias, Vassilios] Medical School, University of Crete, Department of Medical OncologyHeraklion, Crete, Greece.
[Stathopoulos, N Efstathios] Medical School of the University of Crete, Department of Pathology, Voutes, 70003 Heraklion, Crete, Greece.
RP Stathopoulos, NE (reprint author), Medical School of the University of Crete, Department of Pathology, 70003 Heraklion, Greece.
EM stath@med.uoc.gr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 33
EP 41
DI 10.1007/s12253-011-9413-8
PG 9
ER
PT J
AU Varoczy, L
Zilahi, E
Gyetvai,
Kajtar, B
Gergely, L
Sipka, S
Illes,
AF Varoczy, Laszlo
Zilahi, Erika
Gyetvai, Agnes
Kajtar, Bela
Gergely, Lajos
Sipka, Sandor
Illes, Arpad
TI Fc-Gamma-Receptor IIIa Polymorphism and Gene Expression Profile Do Not Predict the Prognosis in Diffuse Large B-cell Lymphoma Treated with R-CHOP Protocol
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diffuse large B-cell lymphoma; Rituximab; Fc-gamma-receptor IIIa polymorphism; Gene expression profile; Treatment response; Survival
ID Diffuse large B-cell lymphoma; Rituximab; Fc-gamma-receptor IIIa polymorphism; Gene expression profile; Treatment response; Survival
AB The addition of rituximab to conventional chemotherapy has significantly improved the treatment outcome in diffuse large B-cell lymphoma. However, differences in treatment response and survival data can be observed independently from the International Prognostic Index scores. The current study evaluated the impact of Fc-gamma-receptor IIIa polymorphism and gene expression profile on the response of DLBCL patients to R-CHOP therapy as well as on their survival results. Fifty-one patients were involved, thirty-two females, nineteen males, their median age was 53.1 years. The FCGR3A polymorphism at the 158. amino acid position determined with PCR method showed the following results: VV: 12 cases (23.5%), VF: 29 cases (56.8%) and FF: 10 cases (19.6%), respectively. There was no significant difference between the treatment responses of the three groups. The event-free survival data were less favorable in the F-allele carriers than in V/V homozygous patients, but without any significancy, and the overall survival curves were almost the same. As for the gene expression profile, 20 patients’ biopsy specimens showed germinal center and 31 showed non-germinal center characteristics. Treatment results did not differ from each other in the two groups. Both the event-free and the overall survival data were more favorable in the GC group, however the differences were not significant. Our results contest the predictive value of Fcgamma-receptor IIIa polymorphism and gene expression profile in diffuse large B-cell lymphoma.
C1 [Varoczy, Laszlo] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. 22., 4032 Debrecen, Hungary.
[Zilahi, Erika] University of Debrecen, Medical and Health Science Center, Regional Laboratory for Immunology, Moricz Zs. 22., 4032 Debrecen, Hungary.
[Gyetvai, Agnes] University of Debrecen, Medical and Health Science Center, Regional Laboratory for Immunology, Moricz Zs. 22., 4032 Debrecen, Hungary.
[Kajtar, Bela] University of Pecs, Department of PathologyPecs, Hungary.
[Gergely, Lajos] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. 22., 4032 Debrecen, Hungary.
[Sipka, Sandor] University of Debrecen, Medical and Health Science Center, Regional Laboratory for Immunology, Moricz Zs. 22., 4032 Debrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. 22., 4032 Debrecen, Hungary.
RP Varoczy, L (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
EM laszlo.varoczy@gmail.com
CR Coiffier B, Reyes F, Groupe d’Etude des Lymphomes de l’Adulte, 2005, Best treatment of agressive non-Hodgkin’s lymphoma: a French perspective. Oncology, Williston Park, 19:7–15
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 43
EP 48
DI 10.1007/s12253-011-9414-7
PG 6
ER
PT J
AU Mahmoodi, M
Nahvi, H
Mahmoudi, M
Kasaian, A
Mohagheghi, MA
Divsalar, K
Nahavandian, B
Jafari, A
Ansarpour, B
Moradi, B
Aghamohammadi, A
Amirzargar, AA
AF Mahmoodi, Majid
Nahvi, Hedayat
Mahmoudi, Mahdi
Kasaian, Amir
Mohagheghi, Mohammad-Ali
Divsalar, Kouros
Nahavandian, Bijan
Jafari, Abbas
Ansarpour, Bita
Moradi, Batoul
Aghamohammadi, Asghar
Amirzargar, Ali-Akbar
TI HLA-DRB1,-DQA1 and -DQB1 Allele and Haplotype Frequencies in Female Patients with Early Onset Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Allele frequency; Breast cancer; Human leukocyte antigen (HLA); HLA-DRB1; HLA-DQA1; HLA-DQB1
ID Allele frequency; Breast cancer; Human leukocyte antigen (HLA); HLA-DRB1; HLA-DQA1; HLA-DQB1
AB Based on the reports, few HLA class II alleles are associated with susceptibility or protection in breast cancer. Here we investigate the association between HLA class II alleles and breast cancer in Iranian women. 100 patients with pathologically proven breast cancer who referred to Cancer Institute were randomly selected and compared with a group of 80 healthy blood donor subjects. The patients were studied in two groups, group 1 includes patients aging 40 years or younger and group 2 include patients aging over 40 years. HLA class II alleles were determined by amplification of DNA followed by HLA-typing using sequence-specific primer (SSP) for each allele. In group 1, the most frequent alleles were HLA-DQA1*0301 (P=0.002, OR=3.3) and HLA-DQB1*0302 (P=0.04, OR=2.8). In group 2, the following alleles increased significantly than those in controls including HLA-DQA1*0301 (P=0.001, OR=3.4) and HLA-DRB1*0301 (P=0.04, OR=2.3). In complete group of patients, the frequency of HLADQA1* 0301 (P=0.001, OR=3.4) and HLA-DRB1*1303 (P=0.02, OR=2.3) increased significantly than those in control group. HLA-DQA1*0505, HLA-DQA1*0101, HLA-DRB1*1301and HLA-DRB1*0101 alleles showed negative association with breast cancer. Our findings suggest that HLA-DQA1*0301 allele is mainly associated with increased risk of breast cancer including early-onset of the disease. HLA-DQA1*0505 and HLA-DRB1*1301 are involved in protection. We conclude that specific alleles of HLA class II influence breast cancer risk.
C1 [Mahmoodi, Majid] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Nahvi, Hedayat] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Mahmoudi, Mahdi] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Kasaian, Amir] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Mohagheghi, Mohammad-Ali] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Divsalar, Kouros] Kerman University of Medical Sciences, Neuroscience Research CenterKerman, Iran.
[Nahavandian, Bijan] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Jafari, Abbas] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Ansarpour, Bita] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Moradi, Batoul] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
[Aghamohammadi, Asghar] Tehran University of Medical Scie, Growth and Development Research CenterTehran, Iran.
[Amirzargar, Ali-Akbar] Tehran University of Medical Sciences, Faculty of Medicine, Department of ImmunologyTehran, Iran.
RP Amirzargar, AA (reprint author), Tehran University of Medical Sciences, Faculty of Medicine, Department of Immunology, Tehran, Iran.
EM amirzara@tums.ac.ir
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 49
EP 55
DI 10.1007/s12253-011-9415-6
PG 7
ER
PT J
AU Li, X
Zhang, Q
He, W
Meng, W
Yan, J
Zhang, L
Zhu, X
Liu, T
Li, Y
Bai, Z
AF Li, Xun
Zhang, Quanbao
He, Wenting
Meng, Wenbo
Yan, Jun
Zhang, Lei
Zhu, Xiaoliang
Liu, Tao
Li, Yumin
Bai, Zhongtian
TI Low Frequency of PIK3CA Gene Mutations in Hepatocellular Carcinoma in Chinese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; PIK3CA; Gene mutation; Hepatitis B virus
ID Hepatocellular carcinoma; PIK3CA; Gene mutation; Hepatitis B virus
AB PI3K/AKT constitutes an important pathway regulating the signaling of multiple biological processes and plays a critical role in carcinogenesis. PIK3CA gene missense mutations have been reported in many human cancer types. The mutation of it in hepatocellular carcinoma cases varies with different races and regions. In this study, we investigated PIK3CA mutation in Chinese hepatocellular carcinoma patients. A total 90 Chinese patients of hepatocellular carcinoma were recruited in this study. Exons 9 and 20 hotspots mutations of PIK3CA gene were detected by PCR-based DNA sequencing. Two point mutations (E542K and D549H) in exon 9 were found in only one patient (1/90; 1.11%), no mutation was found in exon 20 in any cases. 57 patients are associated with HBV infection (57/90; 63.3%), and 8 patients with HCV infection (8/90; 8.9%). The frequency of the PIK3CA mutations in hepatocellular carcinoma seems to be lower in Chinese hepatocellular carcinoma patients. These findings suggest that PI3K mutations may not play a major role in hepatic carcinogenesis in Chinese. HBV infection has close relationship with HCC in Chinese.
C1 [Li, Xun] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Zhang, Quanbao] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[He, Wenting] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Meng, Wenbo] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Yan, Jun] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Zhang, Lei] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Zhu, Xiaoliang] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
[Liu, Tao] Key Laboratory of Digestive System, 730000 Lanzhou, Gansu Province, China.
[Li, Yumin] Key Laboratory of Digestive System, 730000 Lanzhou, Gansu Province, China.
[Bai, Zhongtian] The First Hospital of Lanzhou University, The Second Department of General Surgery, 730000 Lanzhou, China.
RP Li, Y (reprint author), Key Laboratory of Digestive System, 730000 Lanzhou, China.
EM liym@lzu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 57
EP 60
DI 10.1007/s12253-011-9416-5
PG 4
ER
PT J
AU Nikolenyi, A
Uhercsak, G
Csenki, M
Hamar, S
Csorgo, E
Tanczos, E
Thurzo, L
Brodowicz, Th
Wagnerova, M
Kahan, Zs
AF Nikolenyi, Aliz
Uhercsak, Gabriella
Csenki, Melinda
Hamar, Sandor
Csorgo, Erika
Tanczos, Ervin
Thurzo, Laszlo
Brodowicz, Thomas
Wagnerova, Maria
Kahan, Zsuzsanna
TI Tumour Topoisomerase II Alpha Protein Expression and Outcome After Adjuvant Dose-Dense Anthracycline-Based Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anthracyclines; Adjuvant chemotherapy; Breast cancer; Dose-dense chemotherapy; Topoisomerase II alpha
ID Anthracyclines; Adjuvant chemotherapy; Breast cancer; Dose-dense chemotherapy; Topoisomerase II alpha
AB There is a need for the selection of those breast cancers where benefit may be attained from the addition of an anthracycline to the adjuvant chemotherapy. The expression of topoisomerase II alpha (TOP2A) protein in 3 cohorts of breast cancers treated with adjuvant dose-dense anthracycline-based chemotherapy was determined retrospectively. The TOP2A status was analysed in relation with the other standard tumour features and the outcome. TOP2A IHC results were assessable in 106 patients: with a cut-off value of 15%, 48% of the tumours were classified as TOP2A-positive. The expression of TOP2A correlated with that of Ki67 (R=0.532, p<0.001) and a high grade (p=0.04), but did not correlate with the proportion of ER- or PR-positive cells in the tumour. More tumors were TOP2A-negative among the ER- or PR-positive cancers than among the ER/PR-negative cancers (p=0.021 and p=0.002, respectively). After a median follow-up time of 64.5 months, 31 relapses (23.5%) and 23 deaths (17.4%) had occurred in 131 patients. The overall survival was longer in the TOP2A-positive cases than in the TOP2A-negative cases. The recurrence-free survival and the overall survival were significantly more favourable in the ER/PR-negative and TOP2A-positive tumours than in other subgroups. In a Cox proportional hazards model, the grade and TOP2A remained significant determinants in the ER/PR-negative subgroup. TOP2A positivity and grade 3 indicated a decrease in the risk of death with HR=0.211 (95% CI: 0.042–1.05, p=0.056) and HR=0.216 (95% CI: 0.047–0.990, p=0.048), respectively. A higher sensitivity to anthracycline-containing regimens is suggested in ER/PR-negative and TOP2A-positive cancers.
C1 [Nikolenyi, Aliz] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Uhercsak, Gabriella] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Csenki, Melinda] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Hamar, Sandor] University of Szeged, Department of PathologySzeged, Hungary.
[Csorgo, Erika] University of Szeged, Department of PathologySzeged, Hungary.
[Tanczos, Ervin] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Brodowicz, Thomas] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Wagnerova, Maria] Central European Cooperative Oncology GroupVienna, Austria.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM kahan@onko.szote.u-szeged.hu
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Gianni L, Norton L, Wolmark N, Suter TM, Bonadonna G, Hortobagyi GN, 2009, Role of anthracyclines int he treatment of early breast cancer. J Clin Oncol 27:4798–4808
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 61
EP 68
DI 10.1007/s12253-011-9417-4
PG 8
ER
PT J
AU Sugunadevi, G
Suresh, K
Vijayaanand, AM
Rajalingam, K
Sathiyapriya, J
AF Sugunadevi, Govindasamy
Suresh, Kathiresan
Vijayaanand, Arokia Mariadoss
Rajalingam, Kasinathan
Sathiyapriya, Jagadeesan
TI Anti Genotoxic Effect of Mosinone-A on 7, 12-Dimethyl Benz[a] Anthracene Induced Genotoxicity in Male Golden Syrian Hamsters
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chromosomal aberrations; Comet assay; Genotoxicity; DMBA; Micronuclei; Mosinone-A
ID Chromosomal aberrations; Comet assay; Genotoxicity; DMBA; Micronuclei; Mosinone-A
AB The present study was aimed to evaluate the antigenotoxic effect of Mosinone-A on 7,12-dimethylbenz [a]anthracene induced genotoxicity. The frequency of micronucleated polychromatic erythrocytes [MnPCEs], chromosomal aberrations [CA], DNA damage (comet assay) as cytogenetic markers and the status of lipid peroxidation byproducts, antioxidants and phase II detoxification agents were used as biochemical markers to assess the antigenotoxic effect of Mosinone-A on DMBA induced genotoxicity. A single intraperitoneal injection of DMBA (30 mg/kg b.wt) to golden Syrian hamsters, resulted in marked elevation in the frequency of MnPCEs, aberrations in the chromosomal structure were found in bone marrow and DNA damage (comet assay) was found in blood cells and altered level of lipid peroxidation, antioxidants, and phase II detoxification agents. Oral pretreatment of Mosinone-A (2 mg/kg b.wt) for 5 days to DMBA treated animals significantly reduced the frequency of MnPCEs, chromosomal abnormalities such as chromosomal break, gap, minute, fragment, DNA damage and reversed the status of biochemical variables. Our results thus demonstrated the antigenotoxic effect of Mosinone-A on DMBA induced genotoxicity in male golden Syrian hamsters.
C1 [Sugunadevi, Govindasamy] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Suresh, Kathiresan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Vijayaanand, Arokia Mariadoss] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Rajalingam, Kasinathan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Sathiyapriya, Jagadeesan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
RP Suresh, K (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
EM suraj_cks@yahoo.co.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 69
EP 77
DI 10.1007/s12253-011-9418-3
PG 9
ER
PT J
AU Shen, GJ
Xu, YCh
Li, X
Dong, JM
Jiang, NZ
Wang, J
Wang, BL
AF Shen, Guo Jian
Xu, Yang Chao
Li, Xin
Dong, Jun Ming
Jiang, Nong Zi
Wang, Jin
Wang, Bo Lin
TI Dystroglycan is Associated with Tumor Progression and Patient Survival in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adhesion molecule; α-dystroglycan; β-dystroglycan; Gastric cancer; Prognosis
ID Adhesion molecule; α-dystroglycan; β-dystroglycan; Gastric cancer; Prognosis
AB Previous reports had indicated that there was a possible correlation of dystroglycan (DG) with biological behavior of cancer cells and cancer patients’ survival. However, the role of DG expression in gastric cancer was rarely studied. In this study, α-DG and β-DG expression were determined by immunohistochemistry in specimens of primary cancer, metastatic lymph node, distal metastatic lesion, and their normal counterpart tissues in 20 gastric cancer patients. Correlations between α-DG and β-DG expression and prognosis were retrospectively analyzed. Our results found that positive expression of α-DG in normal mucosa, paired primary tumor, metastatic lymph node and distal metastatic site was detected in 95%, 70%, 25%, and 5% specimens, individually. Regarding β-DG,it was 70%, 55%, 10%, and 10%, individually. Patients who had lower α-DG expression in tumors than in normal counterparts showed poor survival (p=0.002), whereas such a correlation was not found in the case of β-DG (p=0.079). Difference of α-DG between primary tumor and its normal counterparts was an independent prognostic factor in gastric cancer with distal metastasis. This study showed DG expression was gradually reduced during tumor progression. Different expression of α-DG, but not β-DG, between primary tumor and normal specimen, correlated with patient survival, implicating a potential marker for gastric cancer prognosis.
C1 [Shen, Guo Jian] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, 310016 Hangzhou, China.
[Xu, Yang Chao] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, 310016 Hangzhou, China.
[Li, Xin] Hangzhou First People’s Hospital, Department of Medical Oncology, 310016 Hangzhou, China.
[Dong, Jun Ming] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, 310016 Hangzhou, China.
[Jiang, Nong Zi] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Wang, Jin] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of PathologyHangzhou, China.
[Wang, Bo Lin] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, 310016 Hangzhou, China.
RP Wang, BL (reprint author), Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, 310016 Hangzhou, China.
EM wanglinbo@medmail.com.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 79
EP 84
DI 10.1007/s12253-011-9419-2
PG 6
ER
PT J
AU Lakatos, G
Sipos, F
Miheller, P
Hritz, I
Varga, ZsM
Juhasz, M
Molnar, B
Tulassay, Zs
Herszenyi, L
AF Lakatos, Gabor
Sipos, Ferenc
Miheller, Pal
Hritz, Istvan
Varga, Zsofia Maria
Juhasz, Mark
Molnar, Bela
Tulassay, Zsolt
Herszenyi, Laszlo
TI The Behavior of Matrix Metalloproteinase-9 in Lymphocytic Colitis, Collagenous Colitis and Ulcerative Colitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Matrix metalloproteinase; Ulcerative colitis; Lymphocytic colitis; Collagenous colitis; Immunohistochemistry; Inflammation
ID Matrix metalloproteinase; Ulcerative colitis; Lymphocytic colitis; Collagenous colitis; Immunohistochemistry; Inflammation
AB Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffinembedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7±19.5%) compared to LC (6.6±9.3%), CC (6.4±7.6%), active diverticulitis (5.33±2.4%), inactive diverticular disease (5.0±2.2%) and controls (6.3±2.6%) (P<0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0±2.8%, moderate: 23.9±3.7%, severe UC: 52.6±3.9% and 6.3±2.6%, respectively, P<0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P<0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P<0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.
C1 [Lakatos, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Miheller, Pal] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Hritz, Istvan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Varga, Zsofia Maria] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Juhasz, Mark] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Molnar, Bela] Hungarian Academy of Science, Clinical Gastroenterology Research UnitBudapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Herszenyi, Laszlo] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
RP Herszenyi, L (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM hersz@bel2.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 85
EP 91
DI 10.1007/s12253-011-9420-9
PG 7
ER
PT J
AU Cappetta, A
Bergamo, F
Mescoli, C
Lonardi, S
Rugge, M
Zagonel, V
AF Cappetta, Alessandro
Bergamo, Francesca
Mescoli, Claudia
Lonardi, Sara
Rugge, Massimo
Zagonel, Vittorina
TI Hepatoid Adenocarcinoma of the Colon: What Should We Target?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatoid adenocarcinoma; Colon cancer; Hepatocellular carcinoma; Alpha-fetoprotein; FOLFOX; FOLFIRI
ID Hepatoid adenocarcinoma; Colon cancer; Hepatocellular carcinoma; Alpha-fetoprotein; FOLFOX; FOLFIRI
AB Hepatoid adenocarcinoma is a rare extra hepatic neoplasm that displays morphological and phenotypic features similar to those of hepatocellular carcinoma. We report a case of a 75-year-old woman, presenting with abdominal pain and complaints of weakness and lost of appetite, who was found to have a mass on her right colon. She underwent right hemicolectomy for a pT3N2M0, stage IIIC colon cancer. The tumor phenotype and immunophenotype, as documented by alpha-fetoprotein immunoreaction positivity, were consistent with adenocarcinoma of hepatoid origin. The patient received FOLFOX-4 regimen as adjuvant treatment, relapsed after six cycles, then was switched to FOLFIRI regimen plus Bevacizumab and progressed after only four cycles. She died 1 month later, eight months after the diagnosis. The lack of any clinical benefit despite an aggressive and multimodal therapeutic strategy, raises a question about what should be targeted when we face this rare disease associated with a very poor prognosis.
C1 [Cappetta, Alessandro] Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 1, Via Gattamelata 64, 35128 Padova, Italy.
[Bergamo, Francesca] Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 1, Via Gattamelata 64, 35128 Padova, Italy.
[Mescoli, Claudia] University of Padua, Department of Diagnostic Medicine and Special Therapies, Pathology Unit 2, Via Gabelli 61, 35121 Padova, Italy.
[Lonardi, Sara] Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 1, Via Gattamelata 64, 35128 Padova, Italy.
[Rugge, Massimo] University of Padua, Department of Diagnostic Medicine and Special Therapies, Pathology Unit 2, Via Gabelli 61, 35121 Padova, Italy.
[Zagonel, Vittorina] Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 1, Via Gattamelata 64, 35128 Padova, Italy.
RP Cappetta, A (reprint author), Veneto Institute of Oncology—IRCCS, Medical Oncology Unit 1, 35128 Padova, Italy.
EM alessandro.cappetta@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 93
EP 96
DI 10.1007/s12253-011-9424-5
PG 4
ER
PT J
AU Kallen, EM
Nunes Rosado, GF
Gonzalez, LA
Sanders, EM
Cates, MMJ
AF Kallen, E Michael
Nunes Rosado, G Flavia
Gonzalez, L Adriana
Sanders, E Melinda
Cates, M M Justin
TI Occasional Staining for p63 in Malignant Vascular Tumors: A Potential Diagnostic Pitfall
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiosarcoma; Hemangioendothelioma; Hemangioma; Kaposi sarcoma; p63
ID Angiosarcoma; Hemangioendothelioma; Hemangioma; Kaposi sarcoma; p63
AB Expression of p63, a putative marker for epithelial or myoepithelial differentiation, has been used to distinguish spindle cell carcinoma from sarcoma. The specificity of p63 for epithelial differentiation has not been thoroughly evaluated however, since p63 expression has been explored in only a handful of mesenchymal tumors. After observing unexpected immunohistochemical staining for p63 in an angiosarcoma of the breast, we evaluated a series of benign and malignant vascular tumors to determine the frequency of such a finding. Nuclear immunoreactivity to p63 was detected, at least focally, in 24% of malignant vascular tumors other than Kaposi sarcoma, which was uniformly negative. Benign vascular tumors were also negative for p63. Although p63 expression in tumors of vascular differentiation is unusual, it may be seen occasionally in some malignant vascular tumors. Thus, p63 is not entirely specific for epithelial differentiation. Since soft tissue angiosarcomas and hemangioendotheliomas sometimes express cytokeratins, the finding of nuclear p63 represents another potential pitfall in the differential diagnosis between poorly-differentiated carcinomas and vascular neoplasms.
C1 [Kallen, E Michael] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 1161 21st Ave. South, Medical Center North C-3322, 37232 Nashville, TN, USA.
[Nunes Rosado, G Flavia] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 1161 21st Ave. South, Medical Center North C-3322, 37232 Nashville, TN, USA.
[Gonzalez, L Adriana] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 1161 21st Ave. South, Medical Center North C-3322, 37232 Nashville, TN, USA.
[Sanders, E Melinda] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 1161 21st Ave. South, Medical Center North C-3322, 37232 Nashville, TN, USA.
[Cates, M M Justin] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 1161 21st Ave. South, Medical Center North C-3322, 37232 Nashville, TN, USA.
RP Cates, MMJ (reprint author), Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 37232 Nashville, USA.
EM justin.m.cates@vanderbilt.edu
CR Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G, 2010, p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol 2(9):a004887
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Moll UM, Slade N, 2004, p63 and p73: roles in development and tumor formation. Mol Cancer Res 2(7):371–386
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Chen SY, Takeuchi S, Urabe K, Hayashida S, Kido M, Tomoeda H, Uchi H, Dainichi T, Takahara M, Shibata S, Tu YT, Furue M, Moroi Y, 2008, Overexpression of phosphorylated-ATF2 and STAT3 in cutaneous angiosarcoma and pyogenic granuloma. J Cutan Pathol 35(8):722–730
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Senoo M, Matsumura Y, Habu S, 2002, TAp63γ, p51A, and dNp63α, p73L), two major isoforms of the p63 gene, exert opposite effects on the vascular endothelial growth factor, VEGF, gene expression. Oncogene 21(16):2455–2465
Chu PG, Weiss LM, 2002, Keratin expression in human tissues and neoplasms. Histopathology 40(5):403–439
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Gill R, O’Donnell RJ, Horvai A, 2009, Utility of immunohistochemistry for endothelial markers in distinguishing epithelioid hemangioendothelioma from carcinoma metastatic to bone. Arch Pathol Lab Med 133(6):967–972
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 97
EP 100
DI 10.1007/s12253-011-9426-3
PG 4
ER
PT J
AU Corradi, D
Alquati, S
Bertoni, F
Bartoli, V
Dei Tos, PA
Wenger, D
Giannini, C
AF Corradi, Domenico
Alquati, Sara
Bertoni, Franco
Bartoli, Veronica
Dei Tos, Paolo Angelo
Wenger, Doris
Giannini, Caterina
TI A Small Intraneural Epithelioid Malignant Peripheral Nerve Sheath Tumour of the Median Nerve Simulating a Benign Lesion. Description of a Case and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Malignant peripheral nerve sheath tumour; Epithelioid variant; Surgical margins; Outcome; Immunohistochemistry
ID Malignant peripheral nerve sheath tumour; Epithelioid variant; Surgical margins; Outcome; Immunohistochemistry
AB The epithelioid variant of malignant peripheral nerve sheath tumours (MPNSTs) is a very rare malignancy. We describe the case of a 30-year-old man complaining of acute pain in his right elbow, mild distal paraesthesias, and some motor deficiencies. He was discovered as having a small fusiform swelling of the median nerve. In view of its very small size, shape, and nonspecific MRI signal, it had initially suggested a benign lesion. The diagnosis of epithelioid MPNST was made only at the histopathological examination. This malignant neoplasm recurred locally fourteen months after surgery. In addition to describe the above very rare case, we have reviewed the literature on epithelioid MPNSTs clearly involving deep major nerve trunks. This case serves as a warning that, even in major nerve trunks, tiny lesions may in reality be early intraneural MPNSTs which, due to their deep location, must be treated adequately with wide margin surgery since the resection margin status represents one of the major parameters influencing the local control of disease and its clinical outcome.
C1 [Corradi, Domenico] University of Parma, Institute of Pathology, Via Gramsci 14, 43126 Parma, Italy.
[Alquati, Sara] Arcispedale S. Maria Nuova, Department of OncologyReggio Emilia, Italy.
[Bertoni, Franco] University of BolognaBologna, Italy.
[Bartoli, Veronica] University of Parma, Institute of Pathology, Via Gramsci 14, 43126 Parma, Italy.
[Dei Tos, Paolo Angelo] Regional Hospital, Department of PathologyTreviso, Italy.
[Wenger, Doris] Mayo Clinic, Department of RadiologyRochester, MN, USA.
[Giannini, Caterina] Mayo Clinic, Department of Laboratory Medicine and PathologyRochester, MN, USA.
RP Corradi, D (reprint author), University of Parma, Institute of Pathology, 43126 Parma, Italy.
EM domenico.corradi@unipr.it
CR Scheithauer B, Louis D, Hunter S et al, 2007, Malignant peripheral nerve sheath tumor, MPNST). In: Louis D, Ohgaki H, Wiestler O et al, eds, WHO classification of tumours of the central nervous system. Lyon, IARC Press
Weiss S, Goldblum J, 2008, Malignant tumors of the peripheral nerves. In: Weiss S, Goldblum J, eds, Enzinger and Weiss’s Soft Tissue Tumors, 5th edn. Mosby, Philadelphia
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 101
EP 106
DI 10.1007/s12253-010-9348-5
PG 6
ER
PT J
AU Papachristou, JD
Goodman, M
Cieply, K
Rao, NMU
AF Papachristou, J Dionysios
Goodman, Mark
Cieply, Kathleen
Rao, N M Uma
TI Extraskeletal Osteosarcoma of Subcutaneous Soft Tissue with Lymph Node and Skin Metastasis: A Case Report with Fluorescence in Situ Hybridization Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Papachristou, J Dionysios] University of Pittsburgh, School of Medicine, Department of PathologyPittsburgh, PA, USA.
[Goodman, Mark] University of Pittsburgh, School of Medicine, Department of OrthopedicsPittsburgh, PA, USA.
[Cieply, Kathleen] University of Pittsburgh, School of Medicine, Department of PathologyPittsburgh, PA, USA.
[Rao, N M Uma] University of Pittsburgh, School of Medicine, Department of PathologyPittsburgh, PA, USA.
RP Papachristou, JD (reprint author), University of Pittsburgh, School of Medicine, Department of Pathology, Pittsburgh, USA.
EM papachristoudj@med.upatras.gr;dip13@pitt.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 107
EP 110
DI 10.1007/s12253-010-9349-4
PG 4
ER
PT J
AU Chen, ChJ
Hsu, HT
Lin, MT
Pintye, M
Chen, JR
AF Chen, Chih-Jung
Hsu, Hui-Ting
Lin, Ming-Tsan
Pintye, Mariann
Chen, Jim-Ray
TI Renal Cell Carcinoma with t(X;17)(p11.2;q25) in a 5-year-old Taiwanese Boy. A Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Chen, Chih-Jung] Changhua Christian Hospital, Department of PathologyChanghua, Taiwan, Republic of China.
[Hsu, Hui-Ting] Changhua Christian Hospital, Department of PathologyChanghua, Taiwan, Republic of China.
[Lin, Ming-Tsan] Changhua Christian Hospital, Department of PediatricChanghua, Taiwan, Republic of China.
[Pintye, Mariann] Chang Gung Memorial Hospital at Keelung, Department of Pathology, No.222, Meijin RdKeelung, Taiwan, Republic of China.
[Chen, Jim-Ray] Chang Gung Memorial Hospital at Keelung, Department of Pathology, No.222, Meijin RdKeelung, Taiwan, Republic of China.
RP Chen, JR (reprint author), Chang Gung Memorial Hospital at Keelung, Department of Pathology, Keelung, Taiwan, Republic of China.
EM jimrchen@cgmh.org.tw
CR Eble JN, Sauter G, Epstein J et al, 2004, WHO Classification of Tumours. Pathology and genetics of tumours of the urinary system and male genital organs. IARC Press, Lyon, pp 37–38
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2012
VL 18
IS 1
BP 111
EP 116
DI 10.1007/s12253-010-9353-8
PG 6
ER
PT J
AU Liu, Ch
AF Liu, Chibo
TI Serum Amyloid A Protein in Clinical Cancer Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Serum amyloid A; SAA; Cancer diagnosis; Proteomics; Inflammation; SELDI-TOF MS
ID Serum amyloid A; SAA; Cancer diagnosis; Proteomics; Inflammation; SELDI-TOF MS
AB The serum amyloid A (SAA) protein is an acute phase protein that is synthesized under the regulation of inflammatory cytokines during both acute and chronic inflammation. It is suggested that the SAA increases correlate with many types of carcinogenesis and neoplastic diseases. Th changes in SAA in serum could therefore indicate the progress and malignancy of the disease, as well as the host responses. The present paper reviewed the rationale of using SAA as potential cancer biomarker in clinical diagnosis, including the contribution and involvement of SAA in cancer growth and development. Then we discussed the current applications of SAA in diagnosis and tracing of different types of cancers. Finally the proteomics techniques, especially the SELDI-TOF MS to identify SAA in serum from patients were appreciated as an important manner in clinical diagnosis.
C1 [Liu, Chibo] Taizhou Municipal Hospital, Department of Clinical Laboratory, 318000 Taizhou, Zhejiang, China.
RP Liu, Ch (reprint author), Taizhou Municipal Hospital, Department of Clinical Laboratory, 318000 Taizhou, China.
EM chibo_liu@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 117
EP 121
DI 10.1007/s12253-011-9459-7
PG 5
ER
PT J
AU Suba, Zs
AF Suba, Zsuzsanna
TI Interplay Between Insulin Resistance and Estrogen Deficiency as co- Activators in Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Insulin resistance; Estrogen deficiency; Carcinogenesis; Obesity; Type-2 diabetes; Growth factor; menopause; sexual steroid; Cardiovascular disease
ID Insulin resistance; Estrogen deficiency; Carcinogenesis; Obesity; Type-2 diabetes; Growth factor; menopause; sexual steroid; Cardiovascular disease
AB Both insulin resistance and estrogen deficiency result in complex metabolic disorder based mainly on defective cellular glucose uptake and on an atherogenic serum lipid profile. These alterations may be regarded as high risks for several life-threatening human diseases, such as type-2 diabetes, cardiovascular lesions and malignancies. Insulin resistance and estrogen deficiency are concomitant disorders with mutual interrelationship. Insulin resistance and the compensatory hyperinsulinemia provoke increased androgen synthesis at the expense of decreased estrogen production. Similarly, a moderate or severe decrease in serum estrogen levels enhances the prevalence of insulin resistant states both in men and women. Healthy premenopausal women enjoy the defensive effect of estrogens against metabolic and hormonal disorders. However, even a slight decrease in their circulatory estrogen levels associated with insulin resistance may increase the risk for cancers, particularly in the organs having high estrogen demand (breast, endometrium and ovary). On the other hand, postmenopausal state with profound estrogen deficiency confers high risk for cancers in different organs with either high or moderate estrogen demand. After menopause, hormone replacement therapy improves insulin sensitivity and decreases the enhanced inclination to malignancies in postmenopausal women. Recognition of the thorough interplay between insulin resistance and estrogen deficiency may illuminate many apparently controversial experimental and clinical findings concerning cancer development and therapeutic possibilities. Moreover, their interactions in the initiation and progression of human malignancies may supply new strategies in primary cancer prevention and cancer cure.
C1 [Suba, Zsuzsanna] National Institute of Oncology, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
RP Suba, Zs (reprint author), National Institute of Oncology, 1122 Budapest, Hungary.
EM subazdr@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 123
EP 133
DI 10.1007/s12253-011-9466-8
PG 11
ER
PT J
AU Koutsaki, M
Zaravinos, A
Spandidos, AD
AF Koutsaki, Maria
Zaravinos, Apostolos
Spandidos, A Demetrios
TI Modern Trends into the Epidemiology and Screening of Ovarian Cancer. Genetic Substrate of the Sporadic Form
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Ovarian cancer; Risk factors; Symptoms; Screening; Oncogenes and onco-suppressor genes
ID Ovarian cancer; Risk factors; Symptoms; Screening; Oncogenes and onco-suppressor genes
AB Ovarian cancer (OC) is a heterogeneous disease, including a broad spectrum of histological subtypes and demonstrating diverse biological behavior. Epithelialderived ovarian malignant tumours constitute the predominant and most lethal form of the disease. Age, genetic predisposition, gynecological and reproductive factors and environmental factors are the main risk factors that increase the risk for acquiring OC. Vaginal examination, ultrasonography and measurement of blood serum levels of tumour markers, especially CA125 constitute the first-line screening modalities for OC, whereas second-line testing involves more accurate imaging techniques such as color Doppler ultrasound of the lesion or/and a CT scan. Sex steroid hormone pathway genes, cell cycle genes, DNA repair genes, oncogenes and onco-suppressor genes have been associated with a genetic susceptibility to sporadic OC. In the present review we focus on the major oncogenes and onco-suppressor genes in the sporadic form of the disease. Each tumour subtype is associated with a unique molecular signature, as revealed by current genetic and biomarker profiling studies. Different OC pathways emerge early in the process of carcinogenesis, ultimately leading to clinically different tumour types. As mutations acquired early during tumourigenesis will be present in all later stages, largescale gene expression profiling using DNA microarray analysis techniques can help to classify ovarian cancers into clinically relevant subtypes.
C1 [Koutsaki, Maria] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
[Zaravinos, Apostolos] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
[Spandidos, A Demetrios] University of Crete, Medical School, Department of Virology, 71110 Heraklion, Crete, Greece.
RP Spandidos, AD (reprint author), University of Crete, Medical School, Department of Virology, 71110 Heraklion, Greece.
EM spandidos@spandidos.gr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 135
EP 148
DI 10.1007/s12253-011-9482-8
PG 14
ER
PT J
AU Halaszlaki, Cs
Takacs, I
Butz, H
Patocs, A
Lakatos, P
AF Halaszlaki, Csaba
Takacs, Istvan
Butz, Henriett
Patocs, Attila
Lakatos, Peter
TI Novel Genetic Mutation in the Background of Carney Complex
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Carney complex; Endocrine overactivity; Genetic study; Regulatory subunit 1A of the protein kinase A; Splice mutation
ID Carney complex; Endocrine overactivity; Genetic study; Regulatory subunit 1A of the protein kinase A; Splice mutation
AB Carney complex is a rare disease inherited in an autosomal dominant manner. It is mostly caused by inactivating mutations of the subunit of protein kinase A. Carney complex is associated with atrial myxoma, nevi or myxomas of the skin, breast tumor and endocrine overactivity. Primary pigmented nodular adrenocortical disease is the specific endocrine manifestation. The authors present the history of a 53-year-old female patient who had undergone surgery for atrial myxomas, thyroid tumor and breast cancer. She was also operated for an adrenal adenoma causing Cushing’s syndrome. Genetic study revealed a novel mutation in the regulatory subunit of protein kinase A (ivs2-1G>A splice mutation in intron 2). Her heterozygous twins were also genetically screened and one of them carried the same mutation. The authors emphasize that despite the absence of specific treatment for patients with Carney complex, confirmation of the diagnosis by genetic studies is important for the close follow-up of the patient and early identification of novel manifestations.
C1 [Halaszlaki, Csaba] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor u. 2/A, 1083 Budapest, Hungary.
[Takacs, Istvan] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor u. 2/A, 1083 Budapest, Hungary.
[Butz, Henriett] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Patocs, Attila] Hungarian Academy of Sciences, Molecular Medicine Research Group, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Lakatos, Peter] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor u. 2/A, 1083 Budapest, Hungary.
RP Halaszlaki, Cs (reprint author), Semmelweis University, 1st Department of Internal Medicine, 1083 Budapest, Hungary.
EM drhalaszlaki@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 149
EP 152
DI 10.1007/s12253-012-9502-3
PG 4
ER
PT J
AU Gurel, D
Kargi, A
Karaman, I
Onen, A
Unlu, M
AF Gurel, Duygu
Kargi, Aydanur
Karaman, Ilgin
Onen, Ahmet
Unlu, Mehtat
TI CD10 Expression in Epithelial and Stromal Cells of Non-small Cell Lung Carcinoma (NSCLC): A Clinic and Pathologic Correlation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD10; Carcinoma; Lung; Stromal cells; Epithelial cells
ID CD10; Carcinoma; Lung; Stromal cells; Epithelial cells
AB CD10 is a zinc dependent metallopeptidase, and its expression in stromal and/or epithelial cells of many carcinomas has been suggested to have prognostic value. This study investigates CD10 expression in epithelial and stromal cells of non small cell lung carcinoma (NSCLC), and evaluates its prognostic value for this tumor and its histologic subtypes. Sixty-six cases of NSCLC [35 cases of nonsquamous cell carcinoma (NSCC) and 31 cases of squamous cell carcinoma (SCC)] were analyzed immunohistochemically for CD10 antibody. Fisher’s exact test and univariate survival analyses were performed. Comparison of clinicopathologic characteristics for NSCLC showed that only stromal CD10 expression had worse prognostic impact, associated with the presence of recurrence (p=0.001), death (p=0.006) and disease positivity (p=0.001). For SCC, CD10 was found to be expressed mainly in the stromal cells, and was associated with a decreased survival (p=0.000) and disease free survival (p=0.000). CD10 expression was restricted to the epithelial cells in NSCC and associated with an increased disease free survival (p=0.036). Stromal CD10 expression apppears to be a worse prognostic factor in NSCLCs. CD10 which is expressed in different cell components of SCC and NSCC appears to have opposing effects on the behaviour of these histologic types.
C1 [Gurel, Duygu] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Kargi, Aydanur] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Karaman, Ilgin] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Onen, Ahmet] Dokuz Eylul University, Faculty of Medicine, Department of Thoracic SurgeryIzmir, Turkey.
[Unlu, Mehtat] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
RP Gurel, D (reprint author), Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Izmir, Turkey.
EM duygu.gurel@deu.edu.tr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 153
EP 160
DI 10.1007/s12253-011-9421-8
PG 8
ER
PT J
AU Chen, ChJ
Lin, SE
Lin, YM
Lin, ShH
Chen, DR
Chen, ChL
AF Chen, Chih-Jung
Lin, Sey-En
Lin, Yueh-Min
Lin, Shu-Hui
Chen, Dar-Ren
Chen, Chi-Long
TI Association of Expression of Kruppel-Like Factor 4 and Kruppel-Like Factor 5 with the Clinical Manifestations of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Immunohistochemistry; KLF4; KLF5; Kruppel-like factor
ID Breast cancer; Immunohistochemistry; KLF4; KLF5; Kruppel-like factor
AB Kruppel-like factors (KLFs) are import modulators of cell proliferation, differentiation, and transformation and have recently been considered possible prognostic factors in breast cancer. In this study, we investigated the correlation between KLF4 and KLF5 expression and the clinical manifestations of breast cancer by immunohistochemical analysis. We observed increased KLF4 and KLF5 expression in tumor cells (invasive and in situ carcinomas), consistent KLF4 and KLF5 expression in in situ and invasive carcinomas, significant associations between KLF4 expression and tumor grade (p=0.033), size (p=0.035) and stage (p=0.006), and an association between KLF5 expression and tumor grade (p=0.033). Interestingly, we observed a relationship between increasing age and KLF4 expression (p=0.007), with a tendency towards greater expression in tumor cells in patients over 50 years old. Moreover, KLF5 nuclear localization was restricted to non-tumor breast ducts and lobules; however, loss of nuclear expression of KLF5 in in situ and invasive carcinomas was observed. Although the mechanism of the loss of KLF5 nuclear expression is not clear, this phenomenon may imply a possible tumorsuppressor-like role for KLF5 in breast cancer tumorigenesis. The expression of KLF4 and KLF5 in breast cancer patients in Taiwan is similar to that in Western countries, except for the uncertainty surrounding its prognostic significance. Further clarification of the underlying mechanisms of KLF4 and KLF5 expression and their correlations with breast cancer outcomes is necessary.
C1 [Chen, Chih-Jung] Taipei Medical University, College of Medicine, Graduate Institute of Clinical Medicine, 250 Wu-Xing Street, 110 Taipei, Taiwan, Republic of China.
[Lin, Sey-En] Taipei Medical University, College of Medicine, Graduate Institute of Clinical Medicine, 250 Wu-Xing Street, 110 Taipei, Taiwan, Republic of China.
[Lin, Yueh-Min] Changhua Christian Hospital, Department of PathologyChanghua, Taiwan, Republic of China.
[Lin, Shu-Hui] Changhua Christian Hospital, Department of PathologyChanghua, Taiwan, Republic of China.
[Chen, Dar-Ren] Changhua Christian Hospital, Department of Surgery, Comprehensive Breast Cancer CenterChanghua, Taiwan, Republic of China.
[Chen, Chi-Long] Taipei Medical University, College of Medicine, Graduate Institute of Clinical Medicine, 250 Wu-Xing Street, 110 Taipei, Taiwan, Republic of China.
RP Chen, ChL (reprint author), Taipei Medical University, College of Medicine, Graduate Institute of Clinical Medicine, 110 Taipei, Taiwan, Republic of China.
EM chencl@tmu.edu.tw
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Beckers J, Herrmann F, Rieger S et al, 2005, Identification and validation of novel ERBB2, HER2, NEU, targets including genes involved in angiogenesis. Int J Cancer 114:590–597
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 161
EP 168
DI 10.1007/s12253-011-9422-7
PG 8
ER
PT J
AU Rasti, M
Arabsolghar, R
Khatooni, Z
Mostafavi-Pour, Z
AF Rasti, Mozhgan
Arabsolghar, Rita
Khatooni, Zahed
Mostafavi-Pour, Zoherh
TI p53 Binds to Estrogen Receptor 1 Promoter in Human Breast Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Estrogen receptor 1; Methylated promoter; p53; Epigenetic
ID Breast cancer; Estrogen receptor 1; Methylated promoter; p53; Epigenetic
AB p53 is a tumor suppressor protein that regulates estrogen receptor 1 (ESR1) expression. To investigate the mechanism of ESR1 gene regulation by p53, chromatin immunoprecipitation was applied to assess the binding of p53, DNMT1, HDAC1 and MeCP2 to both silenced ESR1 promoter in MDA-MB-468 cells and active ESR1 promoter in MCF-7 breast cancer cells. The results of chromatin immunoprecipitation experiments showed that p53 protein binds to both unmethylated CpG island of the ESR1 promoter in the ER-positive MCF-7 and the hypermethylated ESR1 promoter in the ER-negative MDA-MB-468 cells. However, repression complex including DNMT1, HDAC1 and MeCP2 is only associated with silenced ESR1 in ER-negative MDA-MB-468 human breast cancer cells. In addition, ectopically expressed wild type p53 failed to reactivate the ESR1 gene in these cells. These results suggest that specific p53 mutations may contribute to loss of estrogen receptor α expression in breast tumors and also support the hypothesis that mutant p53 is likely to impact DNA methylation.
C1 [Rasti, Mozhgan] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Arabsolghar, Rita] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Khatooni, Zahed] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Mostafavi-Pour, Zoherh] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
RP Rasti, M (reprint author), Shiraz University of Medical Sciences, Department of Biochemistry, Shiraz, Iran.
EM rasti31@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 169
EP 175
DI 10.1007/s12253-011-9423-6
PG 7
ER
PT J
AU Juhasz, E
Beres, J
Kanizsai, Sz
Nagy, K
AF Juhasz, Emese
Beres, Judit
Kanizsai, Szilvia
Nagy, Karoly
TI The Consequence of a Founder Effect: CCR5-Δ32, CCR2-64I and SDF1-3’A Polymorphism in Vlach Gypsy Population in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CCR5; CCR2; SDF1; HIV-1; Gypsy; Hungary
ID CCR5; CCR2; SDF1; HIV-1; Gypsy; Hungary
AB Frequencies of genetic polymorphisms of the three most frequent HIV-1 resistance-conferring alleles playing an important role in HIV-1 pathogenesis were analysed in Vlach Gypsy populations living in Hungary, as the largest minority. Mutations in the encoding genes, such as CCR5-Δ32, CCR2-64I and SDF1-3’A are shown to result in protective effects against HIV-1 infection and disease progression. 560 samples collected from Vlach Gypsy individuals living in 6 North-East Hungarian settlements were genotyped by PCR-RFLP method. Overall allele frequencies of CCR5-Δ32, CCR2-64I and SDF1-3’A were found as 0.122, 0.186 and 0.115 respectively. All the observed genotype frequencies were in accordance with Hardy-Weinberg equilibrium . In regions, however, Vlach Gypsies live in majority and in ethnically homogenous communities, a higher CCR5-Δ32 mutations were found, with allele frequencies of 0.148 and 0.140 respectively, which are remarkably higher than those in general Hungarian people, and ten times higher than in regions of North-Western India from where present day Hungarian Gypsies originated in the Middle Ages. In the background of this higher CCR5-Δ32 allele frequency in the population analysed in our study a genetic founder effect could be assumed. Allele frequency of CCR2-64I was found to be among the highest in Europe. SDF1-3’A allele frequency in Vlach Gypsies was significantly lower than in ethnic Hungarians. 63% of the total 560 individuals tested carried at least one of the mutations studied. These results could partially explain the low incidence of HIV/AIDS among Vlach Gypsies in Hungary.
C1 [Juhasz, Emese] Semmelweis University, Department of Medical Microbiology, Nagyvarad ter 4, 1089 Budapest, Hungary.
[Beres, Judit] National Center for Healthcare Audit and Inspection, Vaci ut 174, 1138 Budapest, Hungary.
[Kanizsai, Szilvia] Semmelweis University, Department of Medical Microbiology, Nagyvarad ter 4, 1089 Budapest, Hungary.
[Nagy, Karoly] Semmelweis University, Department of Medical Microbiology, Nagyvarad ter 4, 1089 Budapest, Hungary.
RP Juhasz, E (reprint author), Semmelweis University, Department of Medical Microbiology, 1089 Budapest, Hungary.
EM juheme@net.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 177
EP 182
DI 10.1007/s12253-011-9425-4
PG 6
ER
PT J
AU Wang, Yx
Lv, H
Li, Zx
Li, C
Wu, Xy
AF Wang, Yue-xiang
Lv, Hui
Li, Ze-xia
Li, Cui
Wu, Xiao-ying
TI Effect of shRNA Mediated Down-Regulation of Annexin A2 on Biological Behavior of Human Lung Adencarcinoma Cells A549
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Annexin A2; Lung cancer; RNA interference; Proliferation; Invasion
ID Annexin A2; Lung cancer; RNA interference; Proliferation; Invasion
AB In the previous study, we found that Annexin A2 was significantly up-regulated in lung cancer and could induce related-antigen in lung cancer patients’ serum. To further study the function of Annexin A2, the short hairpin RNA plasmid targeting Annexin A2 was constructed in vitro and transfected into human lung adencarcinoma A549 cells. Knocking down Annexin A2 expression by shRNA, the mRNA level of Annexin A2 was investigated by semi-quantitative RT-PCR. The expression of Annexin A2 protein was examined by Western Blotting and Immuocytochemistry. MTT assay and Transwell chamber model were used to evaluate proliferation and invasion of A549 cells in vitro. The concentration of matrix metalloproteinase-2 (MMP-2) and cathepsin B (CB) in the supernatant was evaluated by ELISA. At 48 h after transfection, the expression of Annexin A2 mRNA and protein was down-regulated significantly, respectively (p<0.05).The proliferation and invasion capability of A549 cells also decreased significantly (p<0.05). The concentration of MMP-2 and CB was down-regulated obviously, respectively (p<0.05). This study implies that Annexin A2 might play an important role in the progression and invasion of human lung cancer cells, and could promote progression of lung cancer by regulating the expression of MMP-2 and CB.
C1 [Wang, Yue-xiang] Central South University, Xiangya School of Medicine, Department of Medical Ultrastructure, Xiangya Road #110, 410078 Changsha, Hunan, China.
[Lv, Hui] Central South University, Xiangya School of Medicine, Department of Medical Ultrastructure, Xiangya Road #110, 410078 Changsha, Hunan, China.
[Li, Ze-xia] Central South University, Xiangya School of Medicine, Department of Medical Ultrastructure, Xiangya Road #110, 410078 Changsha, Hunan, China.
[Li, Cui] Central South University, Xiangya Hospital, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, 410078 Changsha, Hunan, China.
[Wu, Xiao-ying] Central South University, Xiangya School of Medicine, Department of Medical Ultrastructure, Xiangya Road #110, 410078 Changsha, Hunan, China.
RP Wu, Xy (reprint author), Central South University, Xiangya School of Medicine, Department of Medical Ultrastructure, 410078 Changsha, China.
EM WXY14503@Yahoo.com.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 183
EP 190
DI 10.1007/s12253-011-9427-2
PG 8
ER
PT J
AU Fauzee, JSN
Li, Q
Wang, Yl
Pan, J
AF Fauzee, Jasmine Selimah Nilufer
Li, Qiaozhuan
Wang, Ya-lan
Pan, Juan
TI Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NFκ-B Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PARG; PARP; PI3K/Akt pathway; NFκ-B
ID PARG; PARP; PI3K/Akt pathway; NFκ-B
AB Poly ADP-ribose polymerase (PARP) which is closely related to Poly ADP-ribose glycohydrolase (PARG) has already been thoroughly investigated in both experimental and clinical cancer trials compared to the latter. Nevertheless, in this experiment the importance of PARG expression was highlighted; whereby it is being silenced via lentivirus vector-mediated short hairpin RNA (shRNA). MTT assay showed that there was an inhibition in human Lovo colon cancer cell growth and flow cytometry demonstrated an increase in the population of cells in G0/G1 phase with a decrease in the S phase in transfected Lovo cells. Furthermore, our results suggested that the effect of silencing PARG leads to the inhibition of PARP expression; related to a decrease in the expression of Nuclear Factor Kappa-B (NFκ-B) with an increase in Akt473 phosphorylation; suggesting that the Phosphoinositol 3-kinase (PI3K)/Akt/NFκ-B pathway is important for cellular growth and proliferation. Hence, this study emphasizes and converges on the relevance of silencing PARG which inhibits growth of human colonic cancer cells via PI3K/Akt/NFκ-B pathway; as colon carcinoma remains to be amongst one of the commonest cancers throughout the world with high morbidity and mortality rates.
C1 [Fauzee, Jasmine Selimah Nilufer] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Li, Qiaozhuan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Wang, Ya-lan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
[Pan, Juan] Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
RP Wang, Yl (reprint author), Chongqing Medical University, Molecular Medicine and Cancer Research Center, Department of Pathology, 400016 Chongqing, China.
EM wangyalan074@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 191
EP 199
DI 10.1007/s12253-011-9428-1
PG 9
ER
PT J
AU Cao, X
Xia, Y
Yang, J
Jiang, J
Chen, L
Ni, R
Li, L
Gu, Z
AF Cao, Xiaolei
Xia, Yunfei
Yang, Junling
Jiang, Jinxia
Chen, Li
Ni, Runzhou
Li, Liren
Gu, Zhifeng
TI Clinical and Biological Significance of Never in Mitosis Gene A-Related Kinase 6 (NEK6) Expression in Hepatic Cell Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma (HCC); Nek6; Ki-67; Prognosis
ID Human hepatocellular carcinoma (HCC); Nek6; Ki-67; Prognosis
AB Nek6 is a cell cycle regulatory gene, which can control cell proliferation and survival. Recent studies suggested that desregulation of Nek6 expression plays a key role in oncogenesis. This study was aimed to investigate the potential roles of Nek6 in hepatocellular carcinoma (HCC) development. Immunohistochemistry and Western blot analysis was performed for Nek6 in 80 hepatocellular carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were performed to determine the prognostic significance of Nek6 in HCC. In addition, Nek6 expression vector was used to detect its role in cell cycle control. Nek6 was overexpressed in hepatocellular carcinoma as compared with the adjacent normal tissue. High expression of Nek6 was associated with histological grade and the level of alpha fetal protein, and Nek6 was positively correlated with proliferation marker Ki-67. Univariate analysis showed that Nek6 expression was associated with poor prognosis. Multivariate analysis indicated that Nek6 and Ki-67 protein expression was an independent prognostic marker for HCC. While in vitro, following release from serum starvation of HuH7 HCC cell, the expression of Nek6 was upregulated. Overexpression Nek6 in Huh7 cell could promote the cell cycle. In conclusion, Nek6 is involved in the pathogenesis of hepatocellular carcinoma. It may be a favorable independent poor prognostic parameter for hepatocellular carcinoma.
C1 [Cao, Xiaolei] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, Jiangsu, China.
[Xia, Yunfei] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Yang, Junling] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Jiang, Jinxia] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Chen, Li] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, Jiangsu, China.
[Ni, Runzhou] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Li, Liren] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Gu, Zhifeng] Affiliated Hospital of Nantong University, Department of Internal Medicine, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
RP Li, L (reprint author), Affiliated Hospital of Nantong University, Department of Internal Medicine, 226001 Nantong, China.
EM larry017@163.com
CR Llovet JM, Burroughs A, Bruix J, 2003, Hepatocellular carcinoma. Lancet 362:1907–1917
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 201
EP 207
DI 10.1007/s12253-011-9429-0
PG 7
ER
PT J
AU Gumustekin, M
Kargi, A
Bulut, G
Gozukizil, A
Ulukus, C
Oztop, I
Atabey, N
AF Gumustekin, Mukaddes
Kargi, Aydanur
Bulut, Gulay
Gozukizil, Aysim
Ulukus, Cagnur
Oztop, Ilhan
Atabey, Nese
TI HGF/c-Met Overexpressions, but not Met Mutation, Correlates with Progression of Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE c-Met; HGF; Invasion; Non-small cell lung cancer; RhoA; MMP-2; MMP-9; TIMP-3
ID c-Met; HGF; Invasion; Non-small cell lung cancer; RhoA; MMP-2; MMP-9; TIMP-3
AB Hepatocyte Growth Factor (HGF) and its receptor c-Met are suggested to play an important role in progression of solid organ tumors by mediating cell motility, invasion and metastasis. Overexpression of HGF and c-Met have been shown in non-small-cell lung cancer (NSCLC). However, their role in tumor progression is not clearly defined. The aim of this study is to determine the role of HGF/c-Met pathway and its association with invasion related markers and clinicopathologic parameters in NSCLC. Immunohistochemical analysis was performed on 63 paraffin-embedded NSCLC tumor sections. The expressions of invasion related markers such as Matrix Metalloproteinases (MMPs) 2 and 9, Tissue Inhibitor Metalloproteinase (TIMP) 1 and 3 and RhoA were also examined. Coexpression of HGF/c-Met was significantly associated with lymph node invasion and TIMP-3 and RhoA overexpressions. There were positive correlation between TIMP-3 overexpression and advanced stage and negative correlation between RhoA overexpression and survival. DNA sequencing for Met mutations in both nonkinase and tyrosine kinase (TK) domain was established. A single nucleotide polymorphism (SNP) in sema domain and two SNPs in TK domain of c-Met were found. There was no statistically significant correlation between the presence of c-Met alterations and clinicopathologic parameters except shorter survival time in cases with two SNPs in TK domain. These results suggest that HGF/c-Met might exert their effects in tumor progression in association with RhoA and probably with TIMP-3. The blockade of the HGF/c-Met pathway with RhoA and/or TIMP-3 inhibitors may be an effective therapeutic target for NSCLC treatment.
C1 [Gumustekin, Mukaddes] Dokuz Eylul University, Medical School, Department of PharmacologyInciralti, Izmir, Turkey.
[Kargi, Aydanur] Dokuz Eylul University, Medical School, Department of PathologyInciralti, Izmir, Turkey.
[Bulut, Gulay] Dokuz Eylul University, Medical School, Department of Medical Biology and GeneticsInciralti, Izmir, Turkey.
[Gozukizil, Aysim] Dokuz Eylul University, Medical School, Department of Medical Biology and GeneticsInciralti, Izmir, Turkey.
[Ulukus, Cagnur] Dokuz Eylul University, Medical School, Department of PathologyInciralti, Izmir, Turkey.
[Oztop, Ilhan] Dokuz Eylul University, Medical School, Department of Medical OncologyInciralti, Izmir, Turkey.
[Atabey, Nese] Dokuz Eylul University, Medical School, Department of Medical Biology and GeneticsInciralti, Izmir, Turkey.
RP Atabey, N (reprint author), Dokuz Eylul University, Medical School, Department of Medical Biology and Genetics, Inciralti, Turkey.
EM nese.atabey@deu.edu.tr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 209
EP 218
DI 10.1007/s12253-011-9430-7
PG 10
ER
PT J
AU Karabon, L
Pawlak-Adamska, E
Tomkiewicz, A
Jedynak, A
Kielbinski, M
Woszczyk, D
Potoczek, S
Jonkisz, A
Kuliczkowski, K
Frydecka, I
AF Karabon, Lidia
Pawlak-Adamska, Edyta
Tomkiewicz, Anna
Jedynak, Anna
Kielbinski, Marek
Woszczyk, Dariusz
Potoczek, Stanislaw
Jonkisz, Anna
Kuliczkowski, Kazimierz
Frydecka, Irena
TI Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CTLA-4; Gene polymorphisms; MM
ID CTLA-4; Gene polymorphisms; MM
AB Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic Tlymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p=0.03, 0.65 vs. 0.58, p=0.04, and 0.63 vs. 0.57, p=0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p=0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies.
C1 [Karabon, Lidia] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Pawlak-Adamska, Edyta] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Tomkiewicz, Anna] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Jedynak, Anna] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Kielbinski, Marek] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 1, 50-367 Wroclaw, Poland.
[Woszczyk, Dariusz] Regional Hospital in Opole, Department of Hematology, ul. Kosnego 53Opole, Poland.
[Potoczek, Stanislaw] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 1, 50-367 Wroclaw, Poland.
[Jonkisz, Anna] Medical University, Department of Forensic Medicine, Curie Sklodowskiej 52, 50-369 Wroclaw, Poland.
[Kuliczkowski, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Pasteura 1, 50-367 Wroclaw, Poland.
[Frydecka, Irena] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
RP Karabon, L (reprint author), Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, 53-114 Wroclaw, Poland.
EM lkarabon@iitd.pan.wroc.pl
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Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757, 2003
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Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KM, Smith AN, Di GG, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RC, Howlett S, Healy B, Nutland S, Rance HE, Everett V, Smink LJ, Lam AC, Cordell HJ, Walker NM, Bordin C, Hulme J, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Ronningen KS, Guja C, Ionescu- Tirgoviste C, Savage DA, Maxwell AP, Carson DJ, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SC, 2003, Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423:506–511
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Goldin LR, Pfeiffer RM, Gridley G, Gail MH, Li X, Mellemkjaer L, Olsen JH, Hemminki K, Linet MS, 2004, Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 100:1902–1908
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 219
EP 226
DI 10.1007/s12253-011-9431-6
PG 8
ER
PT J
AU Boonjaraspinyo, S
Boonmars, Th
Kaewkes, S
Laummaunwai, P
Pinlaor, S
Loilome, W
Yongvanit, P
Wu, Z
Puapairoj, A
Bhudhisawasdi, V
AF Boonjaraspinyo, Sirintip
Boonmars, Thidarut
Kaewkes, Sasithorn
Laummaunwai, Porntip
Pinlaor, Somchai
Loilome, Watchalin
Yongvanit, Puangrat
Wu, Zhiliang
Puapairoj, Anucha
Bhudhisawasdi, Vajarabhongsa
TI Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cholangiocarcinoma; Clinicopathology; Retinoblastoma 1; Cyclin D1; Heat shock protein 70; Heat shock protein 90; Histone deacetylase 6
ID Cholangiocarcinoma; Clinicopathology; Retinoblastoma 1; Cyclin D1; Heat shock protein 70; Heat shock protein 90; Histone deacetylase 6
AB Cholangiocarcinoma is a crucial health problem in northeast Thailand. Although rare, it is a highly fatal disease and the prognosis of CCA patients is very poor. To determine if expression of specific genes is useful for diagnosis and prognosis for CCA. We examined the expression of HSP70, HSP90, RB1, cyclin D1, and HDAC6 in 50 resections of human CCA tissues by quantitative real-time PCR. The expression of HSP70, RB1, and HDAC6 was "dominant down-regulation", while the expression of cyclin D1 and HSP90 was "dominant upregulation". There were no correlations between RB1, cyclin D1, HSP90, and clinicopathological parameters such as status, histology type, histological grading, stage of CCA, and metastasis. A significant association was found between HDAC6 and CCA staging (p=0.000), CCA gross type and HSP70 (p=0.046) as well as RB1 expression (p=0.046). Patients with down-regulation of HSP70 had significantly poorer prognosis than those in the upregulation group (p=0.002). Expression of HSP70 may be useful as a new prognostic marker for CCA.
C1 [Boonjaraspinyo, Sirintip] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Boonmars, Thidarut] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Kaewkes, Sasithorn] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Laummaunwai, Porntip] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Pinlaor, Somchai] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Loilome, Watchalin] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Yongvanit, Puangrat] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Wu, Zhiliang] Gifu University, Graduate School of Medicine, Department of Parasitology, 5011194 Gifu, Japan.
[Puapairoj, Anucha] Khon Kaen University, Faculty of Medicine, Department of Pathology, 40002 Khon Kaen, Thailand.
[Bhudhisawasdi, Vajarabhongsa] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
RP Boonmars, Th (reprint author), Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
EM bthida@kku.ac.th
CR International Agency for Research on Cancer, IARC,, 1994, Infection with liver flukes, Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61:121–175
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Sripa B, Pairojkul C, 2008, Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol 24:349–156
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Zhang Z, Yamashita H, Toyama T et al, 2004, HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 10:6962–6968
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 227
EP 237
DI 10.1007/s12253-011-9432-5
PG 11
ER
PT J
AU Abdou, GA
Asaad, YN
Elkased, A
Said, H
Dawoud, M
AF Abdou, Gaber Asmaa
Asaad, Youssef Nancy
Elkased, Ahmed
Said, Hala
Dawoud, Marwa
TI Adult Pancreatic Neuroblastoma, an Unusual Site and Fatal Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroblastoma; Pancreas; Fatal outcome
ID Neuroblastoma; Pancreas; Fatal outcome
AB In this report, we describe a classic case of stroma rich neuroblastoma, nodular type in a 22 year old female presented with a pancreatic mass. This rare and unusual presentation elicits several differential diagnostic categories including solid pseudopapillary tumor, pancreatic endocrine tumor, pancreatoblastoma and PNET. In this report, we tried to differentiate between them depending on the histopathological features and using panel of epithelial and neuroendocrine markers. Although of the rarity of pancreatic neuroblastoma as a primary site of origin, however it should be considered in the differential diagnosis of pancreatic masses in children and young adult. Neuropil and ganglionic differentiation are helpful features to recognize neuroblastoma and differentiate them from other small blue cell tumors. The fatal outcome of adult neuroblastoma confirming the independence of age as a prognostic factor in this neoplasm regardless of stage and histology.
C1 [Abdou, Gaber Asmaa] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
[Asaad, Youssef Nancy] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
[Elkased, Ahmed] Menofiya University, Faculty of Medicine, Department of SurgeryShebein Elkom, Egypt.
[Said, Hala] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
[Dawoud, Marwa] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
RP Abdou, GA (reprint author), Menoufiya University, Faculty of Medicine, Department of Pathology, Shebein Elkom, Egypt.
EM Asmaa_elsaidy@yahoo.com
CR Howman-Giles R, Shaw PJ, Uren RF, Chung DKV, 2007, Neuroblastoma and other neuroendocrine tumors. Semin Nucl Med 37:286–302
David R, Eftekhari F, Lamki N, Shirkhoda A, Fan S, Kumar P, Singleton EB,Madewell JE, 1989, Themany faces of neuroblastoma. Radiographics 5:859–882
Menegaux F, Olshan AF, Reitnauer PJ, Blatt J, Cohn SL, 2005, Positive association between congenital anomalies and risk of neuroblastoma. Pediatr Blood Canc 45:649–655
Tsuji A, Takayanagi M, Kasugai T, Sugimoto H, Shibahara H, Kawasaki H, 2010, A case of adult neuroblastoma with fatal outcome. Nippon Shokakibyo Gakkai Zasshi 107:1651–1660
Vouriot MA, Marchal AL, Olive D, Benz Lemoine E, Schmitt M, Hoeffel JC, 1985, Neuroblastoma of the tail of the pancreas. Apropos of a case. J Radiol 66:547–549
Hoeffel JC, GalloyMA, Schmitt C, SchmittM(1991, Neuroblastoma of the tail of the pancreas in childhood. Br J Radiol 64:167–168
Kumar HR, Sandoval JA, Lovell MA, Fenton LZ, Bealer JF, 2010, Primary pancreatic neuroblastoma: an unusual tumor in infancy. J Pediatr Surg 45:642–646
Lieber MR, Lack EE, Roberts JRJ, Merino MJ, Patterson K, Restrepo C, Solomon D, Chandra R, Triche TJ, 1987, Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases. Am J Surg Pathol 11:85–93
Ehehalt F, Saeger HD, Schmidt CM, Grutzmann R, 2009, Neuroendocrine tumors of the pancreas. Oncologist 14:456– 467
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Luttges J, Pierre E, Zamboni G, Weh G, Lietz H, Kussmann J, Kloppel G, 1997, Malignant non-epithelial tumors of the pancreas. Pathologe 18:233–237
Bulchmann G, Schuster T, Haas RJ, Joppich I, 2000, Primitive neuroectodermal tumor of the pancreas. An extremely rare tumor. Case report and review of the literature. Klin Padiatr 212:185–188
Movahedi-Lankarani S, Hruban RH, Westra WH, Klimstra DS, 2002, Primitive neuroectodermal tumors of the pancreas: a report of seven cases of a rare neoplasm. Am J Surg Pathol 26:1040– 1047
Perek S, Perek A, Sarman K, Tuzun H, Buyukunal E, 2003, Primitive neuroectodermal tumor of the pancreas. A case report of an extremely rare tumor. Pancreatology 3:352–356
Welsch T, Mechtersheimer G, Aulmann S, Mueller SA, Buechler MW, Schmidt J, Kienle P, 2006, Huge primitive neuroectodermal tumor of the pancreas: report of a case and review of the literature. World J Gastroenterol 12:6070–6073
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Nekrep N, Wang J, Miyatsuka T, German MS, 2008, Signals from the neural crest regulate beta-cell mass in the pancreas. Development 135:2151–2160
Plank JL, Mundell NA, Frist AY, LeGrone AW, Kim T, Musser MA, Walter TJ, Labosky PA, 2011, Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation. Dev Biol 349:321–330
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Panovska-Stavridis I, Ivanovski M, Hadzi-Pecova L, Ljatifi A, Trajkov D, Spiroski M, Cevreska L, 2010, A case report of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome. Prilozi 31:349–359
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Slavc I, Ellenbogen R, Jung WH, Vawter GF, Kretschmar C, Grier H, Korf BR, 1990, Myc gene amplification and expression in primary human neuroblastoma. Canc Res 50:1459–1463
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 239
EP 243
DI 10.1007/s12253-011-9434-3
PG 5
ER
PT J
AU Vlachostergios, JP
Karasavvidou, F
Patrikidou, A
Voutsadakis, AI
Kakkas, G
Moutzouris, G
Zintzaras, E
Daliani, DD
Melekos, DM
Papandreou, NCh
AF Vlachostergios, J Panagiotis
Karasavvidou, Foteini
Patrikidou, Anna
Voutsadakis, A Ioannis
Kakkas, Grigorios
Moutzouris, George
Zintzaras, Elias
Daliani, D Danai
Melekos, D Michael
Papandreou, N Christos
TI p53 and Cyclooxygenase-2 Expression are Directly Associated with Cyclin D1 Expression in Radical Prostatectomy Specimens of Patients with Hormone-Naive Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; Cyclooxygenase-2; Cyclin D1; Radical prostatectomy; Prostate cancer; Biochemical failure
ID p53; Cyclooxygenase-2; Cyclin D1; Radical prostatectomy; Prostate cancer; Biochemical failure
AB Prostate cancer (PCa) is a potentially curable disease when diagnosed in early stages and subsequently treated with radical prostatectomy (RP). However, a significant proportion of patients tend to relapse early, with the emergence of biochemical failure (BF) as an established precursor of progression to metastatic disease. Several candidate molecular markers have been studied in an effort to enhance the accuracy of existing predictive tools regarding the risk of BF after RP. We studied the immunohistochemical expression of p53, cyclooxygenase-2 (COX-2) and cyclin D1 in a cohort of 70 patients that underwent RP for early stage, hormone naive PCa, with the aim of prospectively identifying any possible interrelations as well as correlations with known prognostic parameters such as Gleason score, pathological stage and time to prostate-specific antigen (PSA) relapse. We observed a significant (p=0.003) prognostic role of p53, with high protein expression correlating with shorter time to BF (TTBF) in univariate analysis. Both p53 and COX-2 expression were directly associated with cyclin D1 expression (p=0.055 and p=0.050 respectively). High p53 expression was also found to be an independent prognostic factor (p=0.023). Based on previous data and results provided by this study, p53 expression exerts an independent negative prognostic role in localized prostate cancer and could therefore be evaluated as a useful new molecular marker to be added in the set of known prognostic indicators of the disease. With respect to COX-2 and cyclin D1, further studies are required to elucidate their role in early prediction of PCa relapse after RP.
C1 [Vlachostergios, J Panagiotis] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Larissa, Greece.
[Karasavvidou, Foteini] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Pathology, 41110 Biopolis, Larissa, Greece.
[Patrikidou, Anna] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Larissa, Greece.
[Voutsadakis, A Ioannis] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Larissa, Greece.
[Kakkas, Grigorios] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Urology, 41110 Biopolis, Larissa, Greece.
[Moutzouris, George] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Urology, 41110 Biopolis, Larissa, Greece.
[Zintzaras, Elias] University of Thessaly School of Medicine, Department of Biomathematics, 41110 Biopolis, Larissa, Greece.
[Daliani, D Danai] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Larissa, Greece.
[Melekos, D Michael] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Urology, 41110 Biopolis, Larissa, Greece.
[Papandreou, N Christos] University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Larissa, Greece.
RP Vlachostergios, JP (reprint author), University of Thessaly School of Medicine, University Hospital of Larissa, Department of Medical Oncology, 41110 Biopolis, Greece.
EM pvlacho@med.uth.gr
CR Bostwick DG, Grignon DJ, Hammond ME et al, 1999, Prognostic factors in prostate cancer. College of American pathologists consensus statement 1999. Arch Pathol Lab Med 124:995–1000
Brooks JD, Bova GS, Ewing CM et al, 1996, An uncertain role for p53 gene alterations in human prostate cancers. Cancer Res 56:3814–3822
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 245
EP 252
DI 10.1007/s12253-011-9435-2
PG 8
ER
PT J
AU Kandemir, ON
Barut, F
Bektas, S
Ozdamar, OS
AF Kandemir, Onak Nilufer
Barut, Figen
Bektas, Sibel
Ozdamar, Oguz Sukru
TI Can Lymphatic Vascular Density Be Used in Determining Metastatic Spreading Potential of Tumor in Invasive Ductal Carcinomas?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; D2-40; Lymhangiogenesis; Lymphatic vessel invasion
ID Breast carcinoma; D2-40; Lymhangiogenesis; Lymphatic vessel invasion
AB Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p<0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p>0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&E] (p=0.04), number of lymphatic invasion [n/mm2, D2-40] (p=0.001), tumor size (p=0.01), lymph node status (p=0.03), and tumor stage (p=0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor’s biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.
C1 [Kandemir, Onak Nilufer] Zonguldak Karaelmas University, Faculty of Medicine, Department of PathologyZonguldak, Turkey.
[Barut, Figen] Zonguldak Karaelmas University, Faculty of Medicine, Department of PathologyZonguldak, Turkey.
[Bektas, Sibel] Zonguldak Karaelmas University, Faculty of Medicine, Department of PathologyZonguldak, Turkey.
[Ozdamar, Oguz Sukru] Zonguldak Karaelmas University, Faculty of Medicine, Department of PathologyZonguldak, Turkey.
RP Kandemir, ON (reprint author), Zonguldak Karaelmas University, Faculty of Medicine, Department of Pathology, Zonguldak, Turkey.
EM niluferkandemir@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 253
EP 262
DI 10.1007/s12253-011-9436-1
PG 10
ER
PT J
AU Wang, Z
Yuan, X
Jiao, N
Zhu, H
Zhang, Y
Tong, J
AF Wang, Zhu
Yuan, Xin
Jiao, Nanlin
Zhu, Hui
Zhang, Youwei
Tong, Jiandong
TI CDH13 and FLBN3 Gene Methylation are Associated with Poor Prognosis in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Methylation; Prognosis; Microdissection
ID Colorectal cancer; Methylation; Prognosis; Microdissection
AB The aim of this study was to identify potential epigenetic prognostic biomarkers for colorectal cancer (CRC) in the Chinese population. The methylation status of five tumor suppressor genes (CDH13, DLEC1, FBLN3, hMHL1 and RUNX3) was determined using manual microdissection followed by methylation-specific PCR in 85 paired CRC specimens and adjacent normal tissue. The results showed that methylation frequencies in cancerous tissues were 31.8% for CDH13, 37.6% for DLEC1, 38.8% for FBLN3, 22.4% for hMHL1 and 27.1% for RUNX3, all of which were significantly higher than in corresponding normal tissue. Furthermore, CDH13 methylation was associated with poor differentiation (P=0.019) and tended to be predominant in advanced stages (P=0.084); FBLN3 methylation was associated with advanced stages (P=0.027) and lymph node metastasis (P=0.029). Accordingly, the methylation status of CDH13 (P=0.022), FBLN3 (P=0.008), CDH13 and/or FBLN3 (P=0.001) predicted adverse overall survival in CRC, while hMHL1 methylation showed a protective role in survival (P=0.046). Cox proportional hazard models further indicated that CDH13 and/or FBLN3 methylation, but not that of hMHL1, was an independent prognostic factor for CRC. In conclusion, we found CDH13 and FBLN3 gene methylation are potential biomarkers for poor prognosis in CRC.
C1 [Wang, Zhu] The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, Number 368, Mid Hanjiang Road, 225009 Yangzhou, China.
[Yuan, Xin] The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, Number 368, Mid Hanjiang Road, 225009 Yangzhou, China.
[Jiao, Nanlin] Wannan Medical College, Yijishan Hospital, Department of Pathology, 241001 Wuhu, China.
[Zhu, Hui] The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, Number 368, Mid Hanjiang Road, 225009 Yangzhou, China.
[Zhang, Youwei] The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, Number 368, Mid Hanjiang Road, 225009 Yangzhou, China.
[Tong, Jiandong] The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, Number 368, Mid Hanjiang Road, 225009 Yangzhou, China.
RP Tong, J (reprint author), The second Clinical School of Yangzhou University, Yangzhou No.1 People’s Hospital, Department of Oncology, 225009 Yangzhou, China.
EM tongjd1@yahoo.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 263
EP 270
DI 10.1007/s12253-011-9437-0
PG 8
ER
PT J
AU Huang, Z
Hua, D
Hu, Y
Cheng, Z
Zhou, X
Xie, Q
Wang, Q
Wang, F
Du, X
Zeng, Y
AF Huang, Zhaohui
Hua, Dong
Hu, Yu
Cheng, Zhihong
Zhou, Xike
Xie, Qigen
Wang, Qiongyao
Wang, Feng
Du, Xiang
Zeng, Yanjun
TI Quantitation of Plasma Circulating DNA Using Quantitative PCR for the Detection of Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Plasma; Circulating DNA; Quantitative PCR
ID Hepatocellular carcinoma; Plasma; Circulating DNA; Quantitative PCR
AB Circulating DNA is a potential biomarker for tumor diagnosis and prognosis. This study was aimed to quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) using quantitative PCR and evaluate its potential clinical value. Blood samples were collected from 72 patients with HCC, 37 with liver cirrhosis or chronic hepatitis and 41 healthy volunteers. Plasma DNA was extracted and quantified by a real-time quantitative PCR method. The diagnostic and prognostic value of plasma DNA analysis for HCC was evaluated. DNA levels in the HCC plasma (median: 173 ng/mL) were significantly higher than those in the healthy controls (9 ng/mL) or control benign patients (46 ng/mL) (P<0.001). The area under the receiver-operation characteristic (ROC) curve (AUC) assessing plasma DNA was 0.949 for healthy controls and 0.874 for control patients. Plasma DNA detection could discriminate HCC from normal controls with 90.2% sensitivity and 90.3% specificity at the cut-off value of 18.2 ng/mL. Combined ROC analyses using plasma DNA and serum AFP revealed an elevated AUC of 0.974 with 95.1% sensitivity and 94.4% specificity in discriminating HCC from normal controls. The plasma DNA levels were positively associated with tumor size (P=0.012), and were significantly elevated in HCC patients with intrahepatic spreading or vascular invasion (P=0.035). The overall survival time of patients with high plasma DNA levels showed a shortened tread when compared with that of patients with low plasma DNA concentrations (P=0.071). Plasma DNA may be a valuable noninvasive tool for the detecting and predicting the metastasis potential of HCC; and the prognostic value of plasma DNA needed further investigation.
C1 [Huang, Zhaohui] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Hua, Dong] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Hu, Yu] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Cheng, Zhihong] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Zhou, Xike] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Xie, Qigen] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Wang, Qiongyao] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Wang, Feng] The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 200 Huihe Road, 214062 Wuxi, Jiangsu Province, China.
[Du, Xiang] Fudan University Shanghai Cancer Center, Department of Pathology, 270 Dong An Road, 200032 Shanghai, China.
[Zeng, Yanjun] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
RP Huang, Z (reprint author), The Fourth Affiliated Hospital of Suzhou University, Wuxi Oncology Institute, 214062 Wuxi, China.
EM hzhwxsy@126.com
CR El-Serag HB, Rudolph KL, 2007, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576
Farazi PA, DePinho RA, 2006, Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6(9):674– 687
Farinati F, Marino D, De Giorgio M et al, 2006, Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 101(3):524–532
Butt AN, Swaminathan R, 2008, Overview of circulating nucleic acids in plasma/serum. Ann N Y Acad Sci 1137:236–242
Huang ZH, Li LH, Hua D, 2006, Quantitative analysis of plasma circulating DNA at diagnosis and during follow-up of breast cancer patients. Cancer Lett 243(1):64–70
Gal S, Fidler C, Lo YM et al, 2004, Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR. Br J Cancer 90(6):1211–1215
Sozzi G, Conte D, Mariani L et al, 2001, Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res 61(12):4675–4678
Paci M, Maramotti S, Bellesia E et al, 2009, Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer. Lung Cancer 64(1):92–97
Kumar S, Guleria R, Singh V et al, 2010, Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy. Lung Cancer 70(2):211–217
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Huang ZH, Hua D, Du CH et al, 2007, Quantitation of plasma circulating DNA and its clinical value in the diagnosis and prognosis of breast cancer. Maternal Child Health Care China 22, 15):2095–2097
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Gordian E, Ramachandran K, Reis IM et al, 2010, Serum free circulating DNA is a useful biomarker to distinguish benign versus malignant prostate disease. Cancer Epidemiol Biomarkers Prev 19(8):1984–1991
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Lippmann ML, Morgan L, Fein A et al, 1982, Plasma and serum concentrations of DNA in pulmonary thromboembolism. Am Rev Respir Dis 125(4):416–419
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 271
EP 276
DI 10.1007/s12253-011-9438-z
PG 6
ER
PT J
AU Hager, M
Haufe, H
Alinger, B
Kolbitsch, Ch
AF Hager, Martina
Haufe, Heike
Alinger, Beate
Kolbitsch, Christian
TI pS6 Expression in Normal Renal Parenchyma, Primary Renal Cell Carcinomas and their Metastases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kidney cancer; Metastases; Normal renal parenchyma; pS6; Renal cell carcinoma
ID Kidney cancer; Metastases; Normal renal parenchyma; pS6; Renal cell carcinoma
AB In cancer therapy novel concepts focus on phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) inhibitors. In this context, phosphorylated S6 protein of the 40S ribosomal subunit (pS6) overexpression was previously shown to be associated with sensitivity to inhibitors of mTOR. The present study therefore evaluated pS6 expression in normal renal parenchyma (NRP), primary renal cell carcinomas (PRCC) and their metastases. pS6 and pmTOR expression was immunohistochemically analyzed in a tissue microarray (TMA) from localized primary renal cell carcinoma (lPRCC) (n=35), metastasized primary renal cell carcinoma (mPRCC) (n=45), their metastases (n=45), and NRP (n=45). pS6 expression was stronger in mPRCCs and metastases than in NRP and lPRCCs (p<0.05). In mPRCCs high-grade and high-stage tumors showed higher pS6 levels. pS6 overexpression was more frequently found in metastases (40/45; 88.9%) than in mPRCC (24/45; 53.3%) (p<0.05). Overexpression of pS6 in metastases without concomitant overexpression in their primary tumors was found in 16/45 (35.56%) cases. Patients with pS6 overexpression in mPRCCs but also in metastases showed a tendency to shorter overall survival. pS6 score and pmTOR score correlated positively in NRP and in tumorous tissue (mPRCC and metastases). In conclusion, the present study showed stronger pS6 expression and more frequent overexpression in metastases than in corresponding PRCCs. In approximately one-third of the cases pS6 overexpression was found exclusively in metastases, which is interesting with regard to the association between high pS6 expression and sensitivity to mTOR inhibitor therapy.
C1 [Hager, Martina] General Hospital and Paracelsus Medical University Salzburg, Department of Pathology, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
[Haufe, Heike] General Hospital and Paracelsus Medical University Salzburg, Department of Pathology, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
[Alinger, Beate] General Hospital and Paracelsus Medical University Salzburg, Department of Pathology, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
[Kolbitsch, Christian] Innsbruck Medical University (MUI), Department of Anaesthesiology and Intensive Care MedicineInnsbruck, Austria.
RP Hager, M (reprint author), General Hospital and Paracelsus Medical University Salzburg, Department of Pathology, 5020 Salzburg, Austria.
EM hager.martina@gmx.at
CR Dufner A, Thomas G, 1999, Ribosomal S6 kinase signaling and the control of translation. Exp Cell Res 253:100–109
Ferrari S, Bandi HR, Hofsteenge J et al, 1991, Mitogen-activated 70K S6 kinase. Identification of in vitro 40 S ribosomal S6 phosphorylation sites. J Biol Chem 266:22770–22775
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Youssif TA, Fahmy MA, Koumakpayi IH et al, 2011, The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases. Cancer 117:290– 300
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 277
EP 283
DI 10.1007/s12253-011-9439-y
PG 7
ER
PT J
AU Favaro, JW
Hetzl, CA
Reis, OL
Ferreira, U
Billis, A
Cagnon, HAV
AF Favaro, Jose Wagner
Hetzl, Cia Amanda
Reis, Oliveira Leonardo
Ferreira, Ubirajara
Billis, Athanase
Cagnon, Helena A Valeria
TI Periacinar Retraction Clefting in Nonneoplastic and Neoplastic Prostatic Glands: Artifact or Molecular Involvement
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostatic cancer; Histological criteria; Retraction clefting; Dystroglycans; Matrix metalloproteinases; Insulin-like growth factor; Fibroblast growth factor; Vimentin; Laminin; p63
ID Prostatic cancer; Histological criteria; Retraction clefting; Dystroglycans; Matrix metalloproteinases; Insulin-like growth factor; Fibroblast growth factor; Vimentin; Laminin; p63
AB A space between neoplastic acini and prostatic stroma is not rare and studies have interpreted this as an artifact, considering the absence of endothelial cells indicating vascular invasion. Thus, the aims of this work were to characterize and correlate the occurrence and extent of retraction clefting with the reactivities of α and β dystroglycan (αDG, βDG), laminin, matrix metalloproteinase 2 (MMP-2), p63, insulin-like growth factor 1(IGF-1), vimentin, and fibroblast growth factor 2 (FGF-2). The study was based on nonneoplastic and neoplastic prostatic tissues obtained from necropsies and retropubic radical prostatectomies. The results showed that periacinar retraction clefting was significantly more frequent in prostatic carcinoma samples than in normal prostatic acini. Most of the neoplastic acini (72.0%) showed retraction clefting of more than 50% of circumference, which were significantly more frequent in Gleason score 7 and 6. Decreased collagen and reticular and elastic fibers were verified in the stroma around neoplastic acini. Weak and discontinuous αDG, βDG, and laminin immunoreactivities and intensified MMP-2, vimentin, IGF-1 and FGF-2 immunoreactivities were verified in the neoplastic acini; p63 immunoreactivity was negative in all carcinomas. Thus, these findings showed that the lack of epithelial basal cells, DGs, and laminin and increased MMP-2, IGF-1, and FGF-7 could be considered important pathways in periacinar retraction occurrence. This study demonstrated the origin of and the biological mechanisms responsible for periacinar retraction clefting in prostatic carcinoma.
C1 [Favaro, Jose Wagner] Univ Estadual Paulista (UNESP), Institute of Biosciences, Department of Anatomy, CP-510, 18618-970 Botucatu, SP, Brazil.
[Hetzl, Cia Amanda] UNICAMP - University of Campinas, Institute of Biology, Department of Anatomy, Cellular Biology, Physiology and BiophysicsCampinas, SP, Brazil.
[Reis, Oliveira Leonardo] UNICAMP - University of Campinas, School of Medicine, Department of UrologyCampinas, SP, Brazil.
[Ferreira, Ubirajara] UNICAMP - University of Campinas, School of Medicine, Department of UrologyCampinas, SP, Brazil.
[Billis, Athanase] UNICAMP - University of Campinas, School of Medicine, Department of PathologyCampinas, SP, Brazil.
[Cagnon, Helena A Valeria] UNICAMP - University of Campinas, Institute of Biology, Department of Anatomy, Cellular Biology, Physiology and BiophysicsCampinas, SP, Brazil.
RP Favaro, JW (reprint author), Univ Estadual Paulista (UNESP), Institute of Biosciences, Department of Anatomy, 18618-970 Botucatu, Brazil.
EM wjfavaro@ibb.unesp.br
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 285
EP 292
DI 10.1007/s12253-011-9440-5
PG 8
ER
PT J
AU Jiang, W
Wang, Z
Li, X
Fan, X
Duan, Y
AF Jiang, Wei
Wang, Zhiming
Li, Xinying
Fan, Xuegong
Duan, Yankun
TI High-mobility Group Box 1 is Associated with Clinicopathologic Features in Patients with Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma (HCC); Clinicopathology; High-mobility group box 1(HMGB1); Reverse transcription–polymerase chain reaction (RT–PCR); Gene expression
ID Hepatocellular carcinoma (HCC); Clinicopathology; High-mobility group box 1(HMGB1); Reverse transcription–polymerase chain reaction (RT–PCR); Gene expression
AB High-mobility group box 1(HMGB1) has been associated with many human cancers, but the role of HMGB1 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the expression of HMGB1 in human HCC with regard to its clinical significance. Twelve cases of normal liver tissues, 34 cases of HCC and the corresponding liver tissue just around the tumor (LAT) were collected. Then, all the samples were subjected to clinicopathologic examination, reverse transcription–polymerase chain reaction (RT–PCR), Western-blot (WB) and immunohistochemical analysis for the expression of HMGB1. The relationships between HMGB1 mRNA expression and clinicopathologic parameters were analyzed. RT–PCR demonstrated that the expression of relative HMGB1 mRNA (HMGB1/GAPDH) was 0.854±0.172; the highest in the tissue of HCC, significantly up-regulated compared with that of 0.527±0.155 in LAT and of 0.405±0.087 in normal liver tissues (P<0.001). HMGB1 mRNA overexpression was significantly associated with Edmondson stage, TNM stage, vascular invasion and capsule invasion. Western-blot showed the expression of HMGB1 protein in HCC also as the highest among all the groups. Furthermore this overexpression revealed by immunostaining was predominantly localized in the nuclei of HCC; whereas, none of the stains were seen in normal liver cells and only a trace of it was detected in the cytoplasm of LAT cells. Our results suggested the overexpression of HMGB1 might be an important pathogenetic factor in HCC. The mechanisms of HMGB1 in HCC genesis, development and its possible diagnostic and prognostic roles need to be further explored.
C1 [Jiang, Wei] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
[Wang, Zhiming] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
[Li, Xinying] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
[Fan, Xuegong] Central South University, Xiangya Hospital, Department of Infectious Diseases, 410008 Changsha, Hunan, China.
[Duan, Yankun] Central South University, Xiangya Hospital, Department of Infectious Diseases, 410008 Changsha, Hunan, China.
RP Wang, Z (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
EM wzm005@yahoo.com.cn
CR Srivatanakul P, Sriplung H, Deerasamee S, 2004, Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev 5:118–125
Yao DF, Dong ZZ, Yao M, 2007, Specific molecular markers in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 6:241– 247
El-Serag HB, Rudolph KL, 2007, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576
Bosch FX, Ribes J, Cleries R et al, 2005, Epidemiology of hepatocellular carcinoma. Clin Liver Dis 9:191–211
Javaherian K, Liu JF, Wang JC, 1978, Nonhistone proteins HMG1 and HMG2 change the DNA helical structure. Science 199:1345– 1346
Lotze MT, Tracey KJ, 2005, High-mobility group box 1 protein, HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331–342
Czura CJ, Wang H, Tracey KJ, 2001, Dual roles for HMGB1: DNA binding and cytokine. J Endotoxin Res 7:315–321
Muller S, Scaffidi P, Degryse B et al, 2001, New EMBO members’ review: the double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J 20:4337– 4340
Kostova N, Zlateva S, Ugrinova I et al, 2010, The expression of HMGB1 protein and its receptor RAGE in human malignant tumors. Mol Cell Biochem 337:251–258
Akaike H, Kono K, Sugai H et al, 2007, Expression of high mobility group box chromosomal protein-1, HMGB-1, in gastric cancer. Anticancer Res 27:449–457
Brezniceanu ML, Volp K, Bosser S et al, 2003, HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma. FASEB J 17:1295–1297
Wu D, Ding Y, Wang S et al, 2008, Increased expression of high mobility group box 1, HMGB1, is associated with progression and poor prognosis in human nasopharyngeal carcinoma. J Pathol 216:167–175
Liu Y, Xie C, Zhang X et al, 2010, Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer 46:3007–3015
Schlueter C, Weber H, Meyer B et al, 2005, Angiogenetic signaling through hypoxia: HMGB1: an angiogenetic switch molecule. Am J Pathol 166:1259–1263
Dong Xda E, Ito N, Lotze MT et al, 2007, High mobility group box I, HMGB1, release from tumor cells after treatment: implications for development of targeted chemoimmunotherapy. J Immunother 30:596–606
Kuniyasu H, Oue N, Wakikawa A et al, 2002, Expression of receptors for advanced glycation end-products, RAGE, is closely associated with the invasive and metastatic activity of gastric cancer. J Pathol 196:163–170
Edmondson HA, Steiner PE, 1954, Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503
Greene FL, Page DL, Fleming ID et al, 2002, AJCC cancer staging manual, 6th edn. Springer, New York
Thomas JO, Travers AA, 2001, HMG1 and 2, and related ‘architectural’ DNA-binding proteins. Trends Biochem Sci 26:167–174
Ghavami S, Rashedi I, Dattilo BM et al, 2008, S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol 83:1484–1492
Palumbo R, Galvez BG, Pusterla T et al, 2007, Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation. J Cell Biol 179:33–40
Gardella S, Andrei C, Ferrera D et al, 2002, The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesiclemediated secretory pathway. EMBO Rep 3:995–1001
Bonaldi T, Talamo F, Scaffidi P et al, 2003, Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22:5551–5560
Cheng BQ, Jia CQ, Liu CT et al, 2008, Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Dig Liver Dis 40:446–452
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 293
EP 298
DI 10.1007/s12253-011-9442-3
PG 6
ER
PT J
AU Gaida, MM
Bach, TS
Gunther, F
Baseras, B
Tschaharganeh, FD
Welsch, Th
Felix, K
Bergmann, F
Hansch, MG
Wente, NM
AF Gaida, M Matthias
Bach, T Sylvia
Gunther, Frank
Baseras, Billur
Tschaharganeh, F Darjus
Welsch, Thilo
Felix, Klaus
Bergmann, Frank
Hansch, M Gertrud
Wente, N Moritz
TI Expression of Galectin-3 in Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; Galectins; Galectin-3; Expression
ID Pancreatic cancer; Galectins; Galectin-3; Expression
AB Galectin-3 influences neoangiogenesis, tumor cell adhesion, and tumor-immune-escape mechanisms. Hence, the expression of galectin-3 in pancreatic ductal adenocarcinoma (PDAC) was evaluated. Galectin-3 expression in PDAC cell lines was proven by the presence of intracellular protein and by release into the supernatant. Furthermore, galectin-3 was found in the majority of human tissue samples. Serum concentrations of galectin-3 in PDAC patients did not differ significantly from healthy donors and did not correlate with established tumor markers. In conclusion, galectin-3 is expressed in PDAC tissues suggesting a role in tumor development; however, no relationship between expression and clinical findings could be established.
C1 [Gaida, M Matthias] University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
[Bach, T Sylvia] University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
[Gunther, Frank] University of Heidelberg, Institute of Immunology, 69120 Heidelberg, Germany.
[Baseras, Billur] University of Heidelberg, Institute of Immunology, 69120 Heidelberg, Germany.
[Tschaharganeh, F Darjus] University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
[Welsch, Thilo] University of Heidelberg, Department of Surgery, 69120 Heidelberg, Germany.
[Felix, Klaus] University of Heidelberg, Department of Surgery, 69120 Heidelberg, Germany.
[Bergmann, Frank] University of Heidelberg, Department of Pathology, 69120 Heidelberg, Germany.
[Hansch, M Gertrud] University of Heidelberg, Institute of Immunology, 69120 Heidelberg, Germany.
[Wente, N Moritz] University of Heidelberg, Department of Surgery, 69120 Heidelberg, Germany.
RP Wente, NM (reprint author), University of Heidelberg, Department of Surgery, 69120 Heidelberg, Germany.
EM moritz.wente@aesculap.de
CR Jemal A, Siegel R, Xu J, Ward E, 2010, Cancer statistics, 2010. CA Cancer J Clin 60:277–300
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Hittelet A, Legendre H, Nagy N, Bronckart Y, Pector JC, Salmon I, Yeaton P, Gabius HJ, Kiss R, Camby I, 2003, Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration. Int J Cancer 103:370–379
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Zaia PL, Oshima CT, de Oliveira LF, ndrade Scherholz PL, Manoukian FN, 2010, Immunoexpression of galectin-3 in colorectal cancer and its relationship with survival. J Gastrointest Cancer.
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Sakaki M, Fukumori T, Fukawa T, Elsamman E, Shiirevnyamba A, Nakatsuji H, Kanayama HO, 2010, Clinical significance of Galectin-3 in clear cell renal cell carcinoma. J Med Invest 57:152– 157
Vereecken P, Awada A, Suciu S, Castro G, Morandini R, Litynska A, Lienard D, Ezzedine K, Ghanem G, Heenen M, 2009, Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage III and stage IV melanoma patients. Melanoma Res 19:316–320
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Ceyhan GO, Bergmann F, Kadihasanoglu M, Erkan M, Park W, Hinz U, Giese T, Muller MW, Buchler MW, Giese NA, Friess H, 2007, The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis. Gut 56:534– 544
Erkan M, Kleeff J, Esposito I, Giese T, Ketterer K, Buchler MW, Giese NA, Friess H, 2005, Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis. Oncogene 24:4421–4432
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Koopmann J, Thuluvath PJ, Zahurak ML, Kristiansen TZ, Pandey A, Schulick R, Argani P, Hidalgo M, Iacobelli S, Goggins M, Maitra A, 2004, Mac-2-binding protein is a diagnostic marker for biliary tract carcinoma. Cancer 101:1609–1615
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 299
EP 307
DI 10.1007/s12253-011-9444-1
PG 9
ER
PT J
AU Rizvi, AM
Alam, Sh
Mehdi, JS
Ali, A
Batra, S
AF Rizvi, Alam Moshahid
Alam, Shabbir
Mehdi, Jafar Syed
Ali, Asgar
Batra, Swaraj
TI Allelic Loss of 10q23.3, the PTEN Gene Locus in Cervical Carcinoma from Northern Indian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Loss of heterozygosity; Squmaous cell carcinoma; Cervical carcinoma; Tumor suppressor gene
ID Loss of heterozygosity; Squmaous cell carcinoma; Cervical carcinoma; Tumor suppressor gene
AB Cervical cancer is one of the most common malignant diseases affecting women worldwide. Studies on loss of heterozygosity have been made for PTEN gene specific microsatellite markers in malignancies like breast, ovary and lungs and the results have shown a significant association. However the role of this gene is not clearly understood in cervical cancer from Indian population. A total of 135 cervical carcinoma tissues samples were analyzed for loss of heterozygosity. DNA was isolated from the samples and their matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers (D10S198 & D10S192) and one marker (D10S541) in flanking region and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 31 out of 133 (23%) informative cases showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 8% (D10S192) to 13% (D10S198). Loss of heterozygosity was more frequently detected in intragenic region (D10S198 & D10S192) than in flanking region, D10S541 (21% versus 9%). These data argue that PTEN is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.
C1 [Rizvi, Alam Moshahid] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar Marg, 110025 New Delhi, India.
[Alam, Shabbir] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar Marg, 110025 New Delhi, India.
[Mehdi, Jafar Syed] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar Marg, 110025 New Delhi, India.
[Ali, Asgar] Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, Maulana Mohammad Ali Jauhar Marg, 110025 New Delhi, India.
[Batra, Swaraj] LNJP/MAMC Campus, Department of Obstetrics & Gynecology, 110002 New Delhi, India.
RP Rizvi, AM (reprint author), Jamia Millia Islamia, Department of Biosciences, Genome Biology Lab, 110025 New Delhi, India.
EM rizvijmi@gmail.com
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Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R, 1997, PTEN: a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer. Science 275:1943–1947
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Izycka-Swieszewska E, Brzeskwiniewicz M,Wozniak A, Drozynska E, GrajkowskaW, Perek D, Balcerska A, Klepacka T, Limon J, 2010, EGFR, PIK3CA and PTEN gene status and their protein product expression in neuroblastic tumours. Folia Neuropathol 48(4):238– 245
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Orchiston EA, Bennett D, Leslie NR, Clarke RG, Winward L, Downes CP, Safrany ST, 2004, PTEN M-CBR3, a versatile and selective regulator of inositol 1,3,4,5,6-pentakisphosphate, Ins, 1,3, 4,5,6, P5). Evidence for Ins, 1,3,4,5,6)P5 as a proliferative signal. J Biol Chem 279:1116–1122
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Konopka B, Janiec-Jankowska A, Paszko Z, Goluda M, 2004, The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma. J Cancer Res Clin Oncol 130:114–121
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 309
EP 313
DI 10.1007/s12253-011-9446-z
PG 5
ER
PT J
AU Jia, Y
Liu, M
Huang, W
Wang, Z
He, Y
Wu, J
Ren, Sh
Ju, Y
Geng, R
Li, Z
AF Jia, Yitao
Liu, Min
Huang, Wangang
Wang, Zhenbao
He, Yutong
Wu, Jianhua
Ren, Shuguang
Ju, Yingchao
Geng, Ruichao
Li, Zhongxin
TI Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Recombinant human endostatin; Colorectal cancer; Metastasis; Angiogenesis; Lymphangiogenesis
ID Recombinant human endostatin; Colorectal cancer; Metastasis; Angiogenesis; Lymphangiogenesis
AB To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected.Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P<0.01). The density of blood vessels in or around the tumor area was 12.27±1.21 and 22.25±2.69 per field in Endostar-treated mice and controls (P<0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84±0.81 vs. 13.83±1.08, P<0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer.
C1 [Jia, Yitao] Hebei General Hospital, Department of OncologyShijiazhuang, Hebei, China.
[Liu, Min] Hebei General Hospital, Geriatrics Key LaboratoryShijiazhuang, Hebei, China.
[Huang, Wangang] Hebei Medical University, the Forth Hospital, Second Department of SurgeryShijiazhuang, Hebei, China.
[Wang, Zhenbao] Hebei Medical University, the Forth Hospital, Second Department of SurgeryShijiazhuang, Hebei, China.
[He, Yutong] Cancer Institute of Hebei ProvinceShijiazhuang, Hebei, China.
[Wu, Jianhua] Hebei Medical University, the Forth Hospital, Centre of Animal ExperimentShijiazhuang, Hebei, China.
[Ren, Shuguang] Hebei Medical University, the Forth Hospital, Centre of Animal ExperimentShijiazhuang, Hebei, China.
[Ju, Yingchao] Hebei Medical University, the Forth Hospital, Centre of Animal ExperimentShijiazhuang, Hebei, China.
[Geng, Ruichao] Hebei Medical University, the Forth Hospital, Second Department of SurgeryShijiazhuang, Hebei, China.
[Li, Zhongxin] Hebei Medical University, the Forth Hospital, Second Department of SurgeryShijiazhuang, Hebei, China.
RP Jia, Y (reprint author), Hebei General Hospital, Department of Oncology, Shijiazhuang, China.
EM jiayitao1970@yahoo.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 315
EP 323
DI 10.1007/s12253-011-9447-y
PG 9
ER
PT J
AU Bouanene, H
Saibi, W
Mokni, M
Sriha, B
Ben Fatma, L
Ben Limem, H
Ben Ahmed, S
Gargouri, A
Miled, A
AF Bouanene, Houda
Saibi, Walid
Mokni, Moncef
Sriha, Badreddine
Ben Fatma, Leila
Ben Limem, Halima
Ben Ahmed, Slim
Gargouri, Ali
Miled, Abdelhedi
TI Biochemical and Morphological Differences Between CA125 Isolated from Healthy Women and Patients with Epithelial Ovarian Cancer from Tunisian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CA125; Ovarian cancer; Tumor marker; Biochemical characterization; MUC16
ID CA125; Ovarian cancer; Tumor marker; Biochemical characterization; MUC16
AB Analysis of the structure of CA125 is essential for determining the physiological role of this significant tumor antigen. The objectives of this study were: (1) to identify the characteristics of the CA125 isolated from healthy and patient women with epithelial ovarian cancer; and (2) to determine the ferning structure of this antigen. The cancer-derived CA125 antigen (cCA125) purified by gel filtration and affinity chromatography (Concanavalin A) was run on SDS-PAGE and examined using light microscopy and compared with healthy-derived CA125 antigen (hCA125). Both purified antigen cCA125 and hCA125 showed a high molecular mass (> 2,000 kDa) with high mannose glycans. The ferning patterns related to cCA125 and hCA125 revealed distinct differences in the patterns of arborescence. The ferning morphology of cCA125 antigen was denser than that of hCA125 antigen making an obvious difference between cCA125 and hCA125, with respect to length, branching and distribution of crystals. The current study provides the first evidence for a potential functional link between CA125 and its structure which, in the light of a comparison between cCA125 and hCA125, might proof to be of significant biomedical importance in the future.
C1 [Bouanene, Houda] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
[Saibi, Walid] University of Sfax, Centre de Biotechnologie de Sfax, Laboratory of Biomass Valorization and Protein Production in Eucaryotes, B.P. 1177, 3038 Sfax, Tunisia.
[Mokni, Moncef] Farhat Hached Hospital, Department of PathologySousse, Tunisia.
[Sriha, Badreddine] Farhat Hached Hospital, Department of PathologySousse, Tunisia.
[Ben Fatma, Leila] CHU Farhat Hached, Service of OncologySousse, Tunisia.
[Ben Limem, Halima] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
[Ben Ahmed, Slim] CHU Farhat Hached, Service of OncologySousse, Tunisia.
[Gargouri, Ali] University of Sfax, Centre de Biotechnologie de Sfax, Laboratory of Biomass Valorization and Protein Production in Eucaryotes, B.P. 1177, 3038 Sfax, Tunisia.
[Miled, Abdelhedi] CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
RP Bouanene, H (reprint author), CHU Farhat Hached, Laboratory of Biochemistry, 4000 Sousse, Tunisia.
EM bouanenehouda2@yahoo.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 325
EP 330
DI 10.1007/s12253-011-9448-x
PG 6
ER
PT J
AU Maciejczyk, A
Jagoda, E
Wysocka, T
Matkowski, R
Gyorffy, B
Lage, H
Surowiak, P
AF Maciejczyk, Adam
Jagoda, Ewa
Wysocka, Teresa
Matkowski, Rafal
Gyorffy, Balazs
Lage, Hermann
Surowiak, Pawel
TI ABCC2 (MRP2, cMOAT) Localized in the Nuclear Envelope of Breast Carcinoma Cells Correlates with Poor Clinical Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ABCC2; Breast cancer; Immunohistochemistry; Prognosis
ID ABCC2; Breast cancer; Immunohistochemistry; Prognosis
AB Nuclear expression of ABCC2 can be specific for lower differentiated cells and stem cells. The study aimed at examination of ABCC2 expression in breast cancers. The immunohistochemical analyses were performed on 70 samples of breast cancer.We have also studied prognostic value of the ABCC2 mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 1809 breast cancer patients. Immunohistochemical studies demonstrated that ABCC2 expression may be manifested in nuclear envelope of neoplastic cells (ABCC2n) as well as in their cell membrane and cytoplasm (ABCC2c). The univariate and multivariate analyses showed that higher expression of ABCC2n and ABCC2c was typical for cases of a shorter overall survival time. Higher ABBC2n expression was also typical for cases of a shorter disease-free survival and a shorter progression-free time. The KM plotter analysis of the prognostic value of ABCC2 mRNA expression showed that elevated ABCC2 expression was specific for cases of a shorter relapse-free survival only in the estrogen receptor-negative subgroup. The study demonstrated hat breast cancers manifest ABCC2 expression and that it is linked to a less favourable prognosis. Our results suggested that immunohistochemical tests represent a reliable way to detect prognostic value of ABCC2 expression, allowing to demonstrate differences related to subcellular localization of the protein. Cases with nuclear expression of ABCC2 manifested a more aggressive clinical course, which might reflect a less advanced differentiation of neplastic cells, resistance to the applied cytostatic drugs and tamoxifen.
C1 [Maciejczyk, Adam] Lower Silesian Oncology Center, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
[Jagoda, Ewa] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-356 Wroclaw, Poland.
[Wysocka, Teresa] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-356 Wroclaw, Poland.
[Matkowski, Rafal] Wroclaw Medical University, Department of OncologyWroclaw, Poland.
[Gyorffy, Balazs] Hungarian Academy of Sciences - Semmelweis University, 1st Dept. of Pediatrics, Research Laboratory for Pediatrics and Nephrology, Bokay u. 53-54, 1083 Budapest, Hungary.
[Lage, Hermann] Charite University Hospital, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
[Surowiak, Pawel] Lower Silesian Oncology Center, pl. Hirszfelda 12, 53-413 Wroclaw, Poland.
RP Surowiak, P (reprint author), Lower Silesian Oncology Center, 53-413 Wroclaw, Poland.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 331
EP 342
DI 10.1007/s12253-011-9449-9
PG 12
ER
PT J
AU Yan, M
Huang, HY
Wang, T
Wan, Y
Cui, ShD
Liu, Zz
Fan, QX
AF Yan, Min
Huang, Hong-Yan
Wang, Ting
Wan, Yi
Cui, Shu-De
Liu, Zhen-zhen
Fan, Qing-Xia
TI Dysregulated Expression of Dicer and Drosha in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; microRNAs; Dicer; Drosha
ID Breast cancer; microRNAs; Dicer; Drosha
AB Large-scale profiling approaches have revealed global down-regulation of microRNAs (miRNAs) in several human cancer types including breast cancer. Altered expression of Dicer and Drosha, two key enzymes in the miRNA maturation, is believed to be one of the most important mechanisms. By using quantitative real-time RTPCR (QT-PCR), we examined the expression of Dicer and Drosha in 49 pairs of matched human breast cancer tissues. Decreased expression was observed in 53.1% (Dicer), 51.9% (Drosha) and 75.5% (Dicer plus Drosha) breast cancer tissues. In conclusion, the decreased expression of Dicer and Drosha may play a role in down-regulation of miRNAs in breast cancer.
C1 [Yan, Min] First Affiliated Hospital of Zhengzhou University, Department of Oncology, No. 1, East Jianshe Rd, 450003 Zhengzhou, China.
[Huang, Hong-Yan] Affiliated Hospital of Academy of Military Medical Sciences, Department of Breast CancerBeijing, China.
[Wang, Ting] Fourth Military Medical University, Xijing Hospital, Department of Vascular and Endocrine SurgeryXi’an, China.
[Wan, Yi] Fourth Military Medical University, Department of StatisticsXi’an, China.
[Cui, Shu-De] Henan Cancer Hospital, Breast Cancer CenterHenan, China.
[Liu, Zhen-zhen] Henan Cancer Hospital, Breast Cancer CenterHenan, China.
[Fan, Qing-Xia] First Affiliated Hospital of Zhengzhou University, Department of Oncology, No. 1, East Jianshe Rd, 450003 Zhengzhou, China.
RP Fan, QX (reprint author), First Affiliated Hospital of Zhengzhou University, Department of Oncology, 450003 Zhengzhou, China.
EM fanqx2011@yeah.net
CR Jemal A, Siegel R, Xu J, Ward E, 2010, Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300
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Erson AE, Petty EM, 2009, miRNAs and cancer: new research developments and potential clinical applications. Cancer Biol Ther 8(24):2317–2322
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Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM, 2005, MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65, 16):7065–7070
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Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, Urbauer D, Pennacchio LA, Cheng JF, Nick AM, Deavers MT, Mourad-Zeidan A, Wang H, Mueller P, Lenburg ME, Gray JW, Mok S, Birrer MJ, Lopez-Berestein G, Coleman RL, Bar-Eli M, Sood AK, 2008, Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 359(25):2641–2650
Sand M, Gambichler T, Skrygan M, Sand D, Scola N, Altmeyer P, Bechara FG, 2010, Expression levels of the microRNA processing enzymes Drosha and dicer in epithelial skin cancer. Cancer Invest 28(6):649–653
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 343
EP 348
DI 10.1007/s12253-011-9450-3
PG 6
ER
PT J
AU He, Hch
Chen, Jh
Chen, Xb
Qin, Gq
Cai, Ch
Liang, Yx
Han, Zd
Dai, Qsh
Chen, Yr
Zeng, Gh
Zhu, Jg
Jiang, Fn
Zhong, Wd
AF He, Hui-chan
Chen, Jia-hong
Chen, Xi-bin
Qin, Guo-qiang
Cai, Chao
Liang, Yu-xiang
Han, Zhao-dong
Dai, Qi-shan
Chen, Yan-ru
Zeng, Guo-hua
Zhu, Jian-guo
Jiang, Fu-neng
Zhong, Wei-de
TI Expression of Hedgehog Pathway Components is Associated with Bladder Cancer Progression and Clinical Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hedgehog signaling pathway; Sonic hedgehog; Patched; Gli1; Bladder cancer; Prognosis
ID Hedgehog signaling pathway; Sonic hedgehog; Patched; Gli1; Bladder cancer; Prognosis
AB Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P=0.006, 0.006 and 0.008, respectively), venous invasion (P=0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P=0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P=0.002, 0.002 and 0.001, respectively) and overall survival (all P<0.001) than those with negative expression of these three proteins. Univariate and multivariate analysis of prognostic factors in bladder cancer patients indicated that the expression patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic factors (all P<0.001). This is the first report describing about the correlation between Hh pathway and the prognosis of bladder cancer. Expression of Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent normal tissues. The examination of their expression is potentially valuable in prognostic evaluation of bladder cancer.
C1 [He, Hui-chan] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Jia-hong] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Xi-bin] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Qin, Guo-qiang] Southern Medical University, 510515 Guangzhou, China.
[Cai, Chao] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Liang, Yu-xiang] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Han, Zhao-dong] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Dai, Qi-shan] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Chen, Yan-ru] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Zeng, Guo-hua] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510230 Guangzhou, China.
[Zhu, Jian-guo] Guizhou Provincial People’s Hospital, Department of Urology, 550002 Guizhou, China.
[Jiang, Fu-neng] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
[Zhong, Wei-de] Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
RP Zhong, Wd (reprint author), Guangzhou Medical College, Guangzhou First Municipal People’s Hospital, Department of Urology, 510180 Guangzhou, China.
EM wdezhong@21cn.com
CR Kramer MW, Escudero DO, Lokeshwar SD et al, 2011, Association of hyaluronic acid family members, HAS1, HAS2, and HYAL-1, with bladder cancer diagnosis and prognosis. Cancer 117:1197–209
Lei Y, Yan S, Ming-De L et al, 2011, Prognostic significance of Aurora-A expression in human bladder cancer. Acta Histochem 113:514–518
Canesin G, Gonzalez-Peramato P, Palou J et al, 2010, Galectin-3 expression is associated with bladder cancer progression and clinical outcome. Tumour Biol 31:277–285
Pasca di Magliano M, Hebrok M, 2003, Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 3:903– 911
Kameda C, Tanaka H, Yamasaki A, 2009, The Hedgehog pathway is a possible therapeutic target for patients with estrogen receptornegative breast cancer. Anticancer Res 29:871–879
Lauth M, Toftgrd R, 2007, The Hedgehog pathway as a drug target in cancer therapy. urr Opin Investig. Drugs 8:457–461
Laurendeau I, Ferrer M, Garrido D, 2010, Gene expression profiling of the Hedgehog signaling pathway in human meningiomas. Mol Med 16:262–270
Walter K, Omura N, Hong SM, 2010, Overexpression of smoothened activates the sonic hedgehog signaling pathway in pancreatic cancer-associated fibroblasts. Clin Cancer Res 16:1781–1789
Berman DM, Karhadkar SS, Maitra A, 2003, Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425:846–851
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Thayer SP, di Magliano MP, Heiser PW, 2003, Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425:851–856
Yanai K, Nagai S, Wada J, 2007, Hedgehog signaling pathway is a possible therapeutic target for gastric cancer. J SurgOncol 95:55–62
Chen G, Goto Y, Sakamoto R et al, 2011, GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor. Biochem Biophys Res Commun 404:809–815
Kelleher FC. Hedgehog signalling and therapeutics in pancreatic cancer. Carcinogenesis. 2010 In press
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Oue T, Yoneda A, Uehara S et al, 2010, Increased expression of the hedgehog signaling pathway in pediatric solid malignancies. J Pediatr Surg 45:387–392
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Ju B, Spitsbergen J, Eden CJ et al, 2009, Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol Cancer 8:40
Ingham PW, McMahon AP, 2001, Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15:3059–3087
Merchant JL, Saqui-Salces M, El-Zaatari M, 2010, Hedgehog signaling in gastric physiology and cancer. Prog Mol Biol Transl Sci 96:133–156
Morton JP, Mongeau ME, Klimstra DS, 2007, Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc Natl Acad Sci USA 104:5103–5108
Berman DM, Karhadkar SS, Maitra A, 2003, Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumors. Nature 425:846–851
Rush SZ, Abel TW, Valadez JG et al, 2010, Activation of the Hedgehog pathway in pilocytic astrocytomas. Neuro Oncol 12:790–798
Liao X, SiuMK,AuCWet al, 2009)Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30:131–140
Yang Y, Tian X, Xie X et al, 2010, Expression and regulation of hedgehog signaling pathway in pancreatic cancer. Langenbecks Arch Surg 395:515–525
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 349
EP 355
DI 10.1007/s12253-011-9451-2
PG 7
ER
PT J
AU Lau, CP
Wong, YE
AF Lau, C Patrick
Wong, Y Elaine
TI Targeting MET by Tyrosine Kinase Inhibitor Suppresses Growth and Invasion of Nasopharyngeal Carcinoma Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nasopharyngeal carcinoma; MET; Growth; Invasion; Tyrosine kinase inhibitor
ID Nasopharyngeal carcinoma; MET; Growth; Invasion; Tyrosine kinase inhibitor
AB Nasopharyngeal carcinoma (NPC) represents a common cancer in endemic areas with high invasive and metastatic potential. It is now known that the HGF-MET signaling pathway plays an important role in mediating the invasive growth of many different types of cancer, including head and neck squamous cell carcinoma. HGF has been shown to stimulate NPC cell growth and invasion in cell line model. The current study aims at demonstrating the effect of MET inhibition by small molecule tyrosine kinase inhibitor PHA665752 on the growth and invasive potential of NPC cell lines. NPC cell lines were used for immunohistochemistry for the MET protein, as well as western blot analysis on MET together with its downstream cascade signaling proteins after treatment with PHA665752. The effect on cell growth, migration and invasion after PHA665752 treatment was also studied. MET inhibition by PHA665752 resulted in highly significant inhibition on NPC cell growth, migration and invasion in vitro. Down-regulation of phospho-MET, phospho-Akt, phospho-MAPK, phospho-STAT3, cyclin D1, β-catenin and PCNA was detected in NPC cells after PHA665752 treatment. MET inhibition with tyrosine kinase inhibitor resulted in suppression of NPC cell growth and invasive potential via down-regulation of a variety of signaling onco-proteins. MET is an important therapeutic target for NPC that warrants further studies and clinical trials.
C1 [Lau, C Patrick] Hong Kong Cancer Institute, Sir YK Pao Center for Cancer, Department of Clinical OncologyShatin, Hong Kong SAR, China.
[Wong, Y Elaine] Hong Kong Cancer Institute, Sir YK Pao Center for Cancer, Department of Clinical OncologyShatin, Hong Kong SAR, China.
RP Lau, CP (reprint author), Hong Kong Cancer Institute, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Shatin, China.
EM patricklau75@hotmail.com
CR Zur Hausen H, Schulte-Holthausen H, Klein G et al, 1970, EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 228:1056–8
Tao Q, Chan ATC, 2007, Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Rev Mol Med 9:1–24
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Kam MKM, Teo PML, Chau RMC et al, 2004, Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: The Hong Kong experience. Int J Radiat Oncol Biol Phys 60:1440–50
Baujat B, Audry H, Bourhis J et al, 2006, Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64:47–56
Jeffers M, Rong S, Vande Woude GF, 1996, Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/ metastasis. J Mol Med 74:505–13
Birchmeier C, Birchmeier W, Gherardi E et al, 2003, Met, metastasis, motility and more. Nat Rev Mol Cell Bio 4:915–25
Lau PC, Chan AT, 2011, Novel therapeutic target for head and neck squamous cell carcinoma: HGF-MET signaling pathway. Anticancer Drugs 22:665–73
Horikawa T, Sheen T, Takeshita H et al, 2001, Induction of c- Met proto-oncogene by Epstein-Barr Virus Latent Membrane Protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma. Am J Pathol 159:27–33
Qian CN, Guo X, Cao B et al, 2002, Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. Cancer Res 62:589–96
Zhou HY, Wan KF, Ip CK et al, 2008, Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK. FEBS Lett 582:3415–22
Xie LQ, Bian LJ, Li Z et al, 2010, Altered expression of Ecadherin by hepatocyte growth factor and effect on the prognosis of nasopharyngeal carcinoma. Ann Surg Oncol 17:1927–36
Glaser R, Zhang HY, Yao KT et al, 1989, Two epithelial tumor cell lines, HNE-1 and HONE-1, latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci USA 86:9524–8
Lo AK, Lo KW, Tsao SW et al, 2006, Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells. Neoplasia 8:173–80
Paweletz CP, Charboneau L, Bichsel VE et al, 2001, Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene 20:1981–9
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 357
EP 363
DI 10.1007/s12253-011-9452-1
PG 7
ER
PT J
AU Ulamec, M
Dzombeta, T
Cupic, H
Lenicek, T
Davor, T
Kruslin, B
AF Ulamec, Monika
Dzombeta, Tihana
Cupic, Hrvoje
Lenicek, Tanja
Davor, Tomas
Kruslin, Bozo
TI Periacinar Retraction Clefting and D2-40 Expression in Prostatic Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE D2 40; Lymphovascular invasion; Prostatic adenocarcinoma; Retraction clefting
ID D2 40; Lymphovascular invasion; Prostatic adenocarcinoma; Retraction clefting
AB Retraction clefting is known to appear in various types of tumors, but it has only recently been recognized as a specific histological phenomenon. Previously, it was considered merely a laboratory procedure artifact, but lately, there have been some assumptions that peritumoral retractions actually represent lymphatic spaces. In our study, we analyzed neoplastic glands in 52 specimens of prostatic adenocarcinoma. Immunohistochemical analysis was performed using D2-40 antibody, to highlight lymphatic endothelium and thereby differentiate actual lymph vessels or lymphovascular invasion from periacinar retractions. Our results showed that the number of lymph vessels was significantly lower in tumorous tissue compared to adjacent normal prostatic tissue. On the other hand, the number of lymph vessels in tumorous tissue was significantly higher than the number of lymph vessels mimicking periacinar retractions. Overall, the number of lymph vessels mimicking periacinar clefts was particularly low. These results are in accordance with our previous studies, which had shown that periacinar clefting appears due to lack of basal cells and stromal changes around tumorous acini. Also, these results support our hypothesis that retractions do not represent lymph vessels but should be considered a distinct entity, which is proven to be helpful both as diagnostic and predictive factor.
C1 [Ulamec, Monika] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska cesta 29Zagreb, Croatia.
[Dzombeta, Tihana] University of Zagreb, School of Medicine, Department of PathologyZagreb, Croatia.
[Cupic, Hrvoje] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska cesta 29Zagreb, Croatia.
[Lenicek, Tanja] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska cesta 29Zagreb, Croatia.
[Davor, Tomas] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska cesta 29Zagreb, Croatia.
[Kruslin, Bozo] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Vinogradska cesta 29Zagreb, Croatia.
RP Kruslin, B (reprint author), University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, Zagreb, Croatia.
EM bozo.kruslin@kbcsm.hr
CR Halpert B, Schmalhorst WR, 1996, Carcinoma of the prostate in patients 70–79 years old. Cancer 1919:695–698
Halpert B, Sheehan EA, Schmalhorst WR et al, 1963, Carcinoma of the prostate: a survey of 5000 autopsies. Cancer 16:736–742
Kruslin B, Tomas D, Mikuz G, 2011, Periacinar retraction artifact of prostate. Front Biosci 3:226–35
Srigley JR, 2004, Benign mimickers of prostatic adenocarcinoma. Mod Pathol 17:328–48
Herawi M, Parwani AV, Irie J et al, 2005, Small glandular proliferations on needle biopsies: most common benign mimickers of prostatic adenocarcinoma sent in for expert second opinion. Am J Surg Pathol 29:874–80
Ulamec M, Tomas D, Ensinger C et al, 2007, Periacinar retraction clefting in proliferative prostatic atrophy and prostatic carcinoma. J Clin Pathol 60:1098–1101
Kruslin B, Tomas D, Rogatsch H et al, 2003, Periacinar retraction clefting in the prostatic needle core biopsies: an important diagnostic criterion or a simple artifact? Virchows Arch 443:524–7
Kruslin B, Tomas D, Rogatsch H et al, 2005, Correlation of periacinar retraction clefting in needle core biopsies and corresponding prostatectomy specimens of patients with prostatic adenocarcinoma. Int J Surg Pathol 13:67–72
Irie J, Manucha V, Ioffe OB et al, 2007, Artefact as the pathologist’s friend: peritumoral retraction in in situ and infiltrating duct carcinoma of the breast. Int J Surg Pathol 15:53–9
Tomas D, Kruslin B, 2004, The potential value of, myo, fibroblastic stromal reaction in the diagnosis of prostatic adenocarcinoma. Prostate 61:324–331
Tomas D, Ulamec M, Hudolin T et al, 2006, Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate cancer. Prostate Cancer Prostatic Dis 9:414–419
Acs G, Dumoff KL, Solin LJ et al, 2007, Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma. Am J Surg Pathol 31:129–40
Acs G, Paragh G, Chuang ST et al, 2009, The presence of micropapillary features and retraction artifact in core needle biopsy material predicts lymph node metastasis in breast carcinoma. Am J Surg Pathol 33:202–10
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Tomas D, Spajic B, Milosevic M et al, 2011, Extensive retraction artifacts predict biochemical recurrence-free survival in prostatic carcinoma. Histopathology 58:447–54
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Kahn HJ, Marks A, 2002, A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest 82:1255–1257
Kruslin B, Tomas D, Cviko A et al, 2006, Periacinar clefting and p63 immunostaining in prostatic intraepithelial neoplasia and prostatic carcinoma. Pathol Oncol Res 12:205–9
Weinstein MH, Signoretti S, Loda M, 2002, Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. Mod Pathol 15:1302–8
Davis LD, Zhang W, Merseburger A et al, 2002, p63 expression profile in normal and malignant prostate epithelial cells. Anticancer Res 22:3819–25
Roma AA, Magi-Galluzzi C, Kral MA et al, 2006, Peritumoral lymphatic invasion is associated with regional lymph node metastases in prostate adenocarcinoma. Mod Pathol 19:392–8
Cheng L, Bishop E, Zhou H et al, 2008, Lymphatic vessel density in radical prostatectomy specimens. Hum Pathol 39:610–5
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 365
EP 370
DI 10.1007/s12253-011-9453-0
PG 6
ER
PT J
AU Valcz, G
Sipos, F
Krenacs, T
Molnar, J
Patai, V
Leiszter, K
Toth, K
Wichmann, B
Molnar, B
Tulassay, Zs
AF Valcz, Gabor
Sipos, Ferenc
Krenacs, Tibor
Molnar, Jeannette
Patai, V Arpad
Leiszter, Katalin
Toth, Kinga
Wichmann, Barna
Molnar, Bela
Tulassay, Zsolt
TI Increase of α-SMA+ and CK+ Cells as an Early Sign of Epithelial-Mesenchymal Transition during Colorectal Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epithelial–myofibroblast transition; Adenoma–carcinoma sequence; Cytokeratin; Alpha–smooth muscle actin
ID Epithelial–myofibroblast transition; Adenoma–carcinoma sequence; Cytokeratin; Alpha–smooth muscle actin
AB Our aim was to examine cell transition events by detecting the frequency of intrapithelial α-smooth muscle actin (SMA)+/cytokeratin (CK)+ cells during colorectal adenoma–carcinoma sequence, in relation to E-cadherin expression. Our further aim was to determine the proliferative activity of intraepithelial α-SMA+ cells. Histologically healthy, adenoma, and colorectal cancer (CRC) biopsy samples were taken during routine colonoscopy and were included into tissue microarrays (TMAs). Slides immunostained for Ki-67, α-SMA, E-cadherin and pan-cytokeratin were digitalized and analyzed by using a digital microscope software. The proportion of α-SMA+/CK+ cells was significantly higher in CRC samples (3.34±1.01%) compared to healthy (1.94±0.69%) or adenoma (1.62±0.78%) samples (p<0.01). E-cadherin expression negatively correlated with the number of α-SMA+ cells. The majority of intraepithelial α-SMA+ cells were in the proliferative phase. During tumor progression, the appearance of dot-like α-SMA staining in CK positive cells may indicate the initial phase of the epithelial-tomesenchymal transition (EMT). The high proportion of intraepithelial α-SMA+ proliferating cells may refer to their increased plasticity compared to differentiated cells. The negative correlation between E-cadherin and intraepithelial α-SMA expression suggests that EMT is facilitated by a loss of epithelial cell contact.
C1 [Valcz, Gabor] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Molnar, Jeannette] National Institute of Food and Nutrition ScienceBudapest, Hungary.
[Patai, V Arpad] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Leiszter, Katalin] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Toth, Kinga] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Wichmann, Barna] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Molnar, Bela] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Tulassay, Zsolt] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
RP Valcz, G (reprint author), Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary.
CR Schultheiss G, Diener M, 1998, K+ and Cl- conductances in the distal colon of the rat. Gen Pharmacol 31:337–342
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Thiery JP, Acloque H, Huang RYet al, 2009, Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890
Kalluri R,Weinberg RA, 2009, The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428
Kalluri R, 2009, EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 119:1417–1419
Hugo H, Ackland ML, Blick T et al, 2007, Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213:374–383
Radisky DC, 2005, Epithelial-mesenchymal transition. J Cell Sci 118:4325–4326
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Miyazono K, 2009, Transforming growth factor-beta signaling in epithelial-mesenchymal transition and progression of cancer. Proc Jpn Acad Ser B Phys Biol Sci 85:314–323
Masszi A, Speight P, Charbonney E et al, 2010, Fate-determining mechanisms in epithelial-myofibroblast transition: major inhibitory role for Smad3. J Cell Biol 188:383–399
Masszi A, Fan L, Rosivall L, McCulloch CA et al, 2004, Integrity of cell-cell contacts is a critical regulator of TGF-beta 1-induced epithelial-to-myofibroblast transition: role for beta-catenin. Am J Pathol 165:1955–1967
Reichert M, Muller T, Hunziker W, 2000, The PDZ domains of zonula occludens-1 induce an epithelial to mesenchymal transition of Madin-Darby canine kidney I cells. Evidence for a role of betacatenin/ Tcf/Lef signaling. J Biol Chem 275:9492–9500
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Ng YY, Huang TP, Yang WC et al, 1998, Tubular epithelialmyofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 54:864–876
Zhou BP, Deng J, Xia W et al, 2004, Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelialmesenchymal transition. Nat Cell Biol 6:931–940
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Masszi A, Di Ciano C, Sirokmany G et al, 2003, Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition. Am J Physiol Renal Physiol 284:911–924
Pino MS, Kikuchi H, Zeng M et al, 2010, Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology 138:1406–1417
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 371
EP 376
DI 10.1007/s12253-011-9454-z
PG 6
ER
PT J
AU Gong, L
Cui, Z
Yu, X
Wei, Y
Peng, J
Leng, X
AF Gong, Lei
Cui, Zhuqingqing
Yu, Xin
Wei, Yuhua
Peng, Jirun
Leng, Xisheng
TI Hexokinase II in CD133+ and CD133- Hepatoma BEL-7402 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatoma; CD133; Hexokinase II; BEL- 7402; Therapeutic target
ID Hepatoma; CD133; Hexokinase II; BEL- 7402; Therapeutic target
AB Hexokinase II is a key enzyme in the glycolytic pathway and CD133+ human hepatoma cells possess cancer stem cell-like properties. The expression and enzyme activity of hexokinase II in CD133+ and CD133- hepatoma cells were examined. CD133 on the surface of the hepatoma BEL-7402 cells was analyzed by flow cytometry and the cells were magnetically sorted into CD133+ and CD133- groups. CD133+ cells comprised 1.04% of the total BEL-7402 cell population. Reverse transcription-polymerase chain reaction (PCR) and quantitative real-time PCR were used to assay the expression of hexokinase II mRNA in these two groups. The level of mRNA in CD133- cells was 4.35 times greater than the level in CD133+ cells. 3,6-biphosphoglucose dehydrogenasecoupled colorimetric method and temperature-sensitive trials were applied to determine the enzyme activity of hexokinase II, which was 1.02 U/g protein in CD133+ cells and 2.47 U/g protein in CD133- cells. Hexokinase II was the major active hexokinase isoform in CD133+ cells, comprising 92.7% of the overall cellular hexokinase activity. The results indicate that hexokinase II is vitally meaningful for CD133+ hepatoma BEL-7402 cells. Hexokinase II represents a new therapeutic target for treating CD133+ hepatoma cells.
C1 [Gong, Lei] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
[Cui, Zhuqingqing] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
[Yu, Xin] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
[Wei, Yuhua] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
[Peng, Jirun] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
[Leng, Xisheng] Peking University People’s Hospital, Department of Hepatobiliary Surgery, No. 11 South Xizhimen Street, Xicheng District, 100044 Beijing, China.
RP Leng, X (reprint author), Peking University People’s Hospital, Department of Hepatobiliary Surgery, 100044 Beijing, China.
EM lengxs2003@126.com
CR Yin AH, Miraglia S, 1997, AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012
Shmelkov SV, Clair R, 2005, AC133/CD133/Prominin-1. Int J Biochem Cell Biol 37:715–719
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Hermann PC, Huber SL, 2007, Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323
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Collins AT, Barry PA, 2005, Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946– 10951
Suetsugu A, Nagaki M, 2006, Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem and Biophys Res Comm 351:820–824
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Pedersen PL, Mathupala S, 2002, Mitochondrial bound type II hexokinase: a key player in the growth and survival of many cancers and an ideal prospect for therapeutic intervention. Biochim Biophys Acta 1555:14–20
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Ihrlund LS, Hernlund E, Khan O et al, 2008, 3-Bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs. Mol Oncol 2:94–101
Mathupala SP, Ko YH, Pedersen PL, 2010, The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies. Biochim Biophys Acta 1797:1225–1230
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 377
EP 381
DI 10.1007/s12253-011-9455-y
PG 5
ER
PT J
AU Singh, A
Mishra, KA
Ylaya, K
Hewitt, MS
Sharma, ChK
Saxena, S
AF Singh, Avninder
Mishra, Kumar Ashwani
Ylaya, Kris
Hewitt, M Stephen
Sharma, Chand Karam
Saxena, Sunita
TI Wilms Tumor-1, Claudin-1 and Ezrin Are Useful Immunohistochemical Markers That Help to Distinguish Schwannoma from Fibroblastic Meningioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarkers; Fibroblastic meningioma; Immunohistochemistry; Schwannoma; Tissue microarray
ID Biomarkers; Fibroblastic meningioma; Immunohistochemistry; Schwannoma; Tissue microarray
AB The aim of this study is to identify immunohistochemical (IHC) markers that can reliably separate schwannoma (SCHW) and fibroblastic meningioma (FM). We selected 106 cases of intracranial SCHW (n=56) and FM (n=50) and constructed a tissue microarray (TMA) of core diameter of 1.0 mm from archival formalin-fixed paraffin-embedded tissue. ATMA-IHC was performed using 14 antibodies. After IHC staining, 98 cores were found suitable for evaluation. The IHC staining was scored as 0–2+ (0, negative; 1+, weak and/or focal 2+ strong and/or diffuse positive). A discriminant analysis (DA) (Wilks’Lambda test) was performed to assess the relative importance of these biomarkers in classifying the two groups FM and SCHW. It showed that WT-1 (Wilks’λ 0.085, p<0.001), EMA (Wilks’λ 0.253, p<0.001), S100 (Wilks’λ 0.487, p<0.001), Claudin-1 (Wilks’ λ 0.57, p<0.001) and Ezrin (Wilks’λ 0.656, p<0.001), SPARC (Wilks’λ 0.751, p<0.01), NP-Y (Wilks’λ, 0.819, p<0.001) and EGFR (Wilks’λ 0.845, p=0.026) were some of the statistically significant markers that discriminated SCHW and FM. For sensitivity and specificity for SCHW the significant markers [Area under the curve (95% CI), p-value] by ROC analysis were WT-1 [0.990(0.000, 1.000), <0.001], S100 [0.880(0.808, 0.951), <0.001] while for diagnosing FM the most sensitive and specific markers were EMA [0.957(0.914, 1.000), <. 001], Claudin-1 [0.857(0.782, 0.932), <0.001] and ezrin [0.792(0.700,0.884),<0.001]. WT-1, Claudin-1 and Ezrin may be potentially useful immunohistochemical adjuncts to EMA and S100 that differentiate SCHW from FM.
C1 [Singh, Avninder] National Institute of Pathology (ICMR), Safdarjung Hospital Campus, Room 602, 6th floor, 110029 New Delhi, India.
[Mishra, Kumar Ashwani] National Institute of Pathology (ICMR), Safdarjung Hospital Campus, Room 602, 6th floor, 110029 New Delhi, India.
[Ylaya, Kris] National Institutes of Health, National Cancer Institute, TARP LabBethesda, MD, USA.
[Hewitt, M Stephen] National Institutes of Health, National Cancer Institute, TARP LabBethesda, MD, USA.
[Sharma, Chand Karam] Safdarjung Hospital, Department of NeurosurgeryNew Delhi, India.
[Saxena, Sunita] National Institute of Pathology (ICMR), Safdarjung Hospital Campus, Room 602, 6th floor, 110029 New Delhi, India.
RP Singh, A (reprint author), National Institute of Pathology (ICMR), Safdarjung Hospital Campus, 110029 New Delhi, India.
EM dravninder@yahoo.co.in
CR Louis DN, Scheithauer BW, Budka H, von Deimling A et al, 2000, Meningiomas. In: Kleihues P, Cavenee WK, eds, Tumours of the nervous system. IARC, Lyon, pp 176–184
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Theaker JM, Gatter KC, Esiri MM, Fleming KA, 1986, Epithelial membrane antigen and cytokeratin expression by meningiomas: an immunohistological study. J Clin Pathol 39:435–439
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Sloan JP, Ormerod MG, 1981, Distribution of epithelial membrane antigen in normal and neoplastic tissues and its value on diagnosis on diagnostic tumor pathology. Cancer 47:1786–1795
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Bhattacharjee M, Adesina AM, Goodman C, Powell S, 2003, Claudin-1 expression in meningiomas and schwannomas: possible role in differential diagnosis [abstract]. J Neuropathol Exp Neurol 62:581
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Martinez-Glez V, Hernandez-Franco C, Rey JA, 2008, Microarray gene expression profiling in meningiomas and schwannnomas. Curr Med Chem 15:826–833
Welling DB, Lasak JM, Akhmametyeva A, Ghaheri B, Chang LS, 2002, A cDNA microarray analysis of vestibular schwannomas. Otol Neurotol 23:736–748
Fine SW, McClain SA, Maomi L, 2004, Immunohistochemical staining for calretinin is useful for differentiating schwannomas from neurofibromas. Am J Clin Pathol 122:552–559
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Omulecka A, Papierz W, Nawrocka-Kunecka A, Lewy-Trenda I, 2006, Immunohistochemical expression of progesterone and estrogen receptors in meningiomas. Folia Neuropathol 44:111– 115
Jaiswal S, Agrawal V, Jaiswal AK, Pandey R, Mahapatra AK, 2009, Expression of estrogen and progesterone receptors in vestibular schwannomas and their clinical significance. J Negat Results Biomed 8:9
Dalgorf DM, Roswell C, Bilbao JM, Chen JM, 2008, Immunohistochemical investigation of hormone receptors and vascular growth factor concentration in vestibular schwannomas. Skull Base 18:377–384
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 383
EP 389
DI 10.1007/s12253-011-9456-x
PG 7
ER
PT J
AU Nemeth, BI
Tiszlavicz, L
AF Nemeth, Balazs Istvan
Tiszlavicz, Laszlo
TI Biphenotypic Surface Epithelial Cells in the Gastrointestinal Tube with Mixed Epithelial-Myofibroblastic Differentiation: A Paradigm
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myofibroblast; Actin; Stem cell
ID Myofibroblast; Actin; Stem cell
AB Epithelial cells and myofibroblasts are wellcharacterized histomorphological elements of tissues. They are distinguished from one another on the basis of topography and of differences in cytokeratin (CK) and α-smooth muscle actin (SMA) expression. Certain epithelial cells exhibit CK / SMA co-expression. This study aimed to define the immunophenotypical characteristics of these biphenotypic cells with respect to cytodifferentiation (broad spectrum of CKs, SMA), cell-cell interaction (E-cadherin, adenomatous polyposis coli - APC, β-catenin), and cell survival (cyclooxygenase-2 - Cox-2). At the routine gastrointestinal pathology service of the Department of Pathology, University of Szeged, tissue samples were identified from instances of cervical inlet patch (n=5), Barrett’s esophagus (n=5), gastritis (n=5), fundic gland polyp (n=2), gastric neoplastic polyp (n=1), inflammatory bowel disease (n=5), and colonic neoplastic polyp (n=3). that contained epithelial cells expressing SMA. These biphenotypic cells were further immunophenotyped. Foregut-derived biphenotypic cells expressed CKs 7 and 20, while hindgut-derived biphenotypic cells expressed only CK 20. Subepithelial myofibroblasts adjacent to biphenotypic epithelium expressed Cox-2, SMA, and β-catenin, as did biphenotypic cells. Myofibroblasts, however, did not express CKs. In neoplastic polyps, APC expression weakened as cytologic atypism increased, while intermingled biphenotypic cells in neoplastic glands overexpressed APC, as did myofibroblasts beneath. CK subspecies expression in biphenotypic cells reflects embryonic development of the gastrointestinal tract. The immunophenotyping analysis addresses bidirectional (via transdifferentiation from epithelia into myofibroblasts or vice versa) formation of biphenotypic cells within damaged epithelium, a phenomenon that must be further analysed.
C1 [Nemeth, Balazs Istvan] University of Szeged, Department of Pathology, 6720 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, 2 Allomas Street, 6720 Szeged, Hungary.
RP Nemeth, BI (reprint author), University of Szeged, Department of Pathology, 6720 Szeged, Hungary.
EM nemeth.istvan.balazs@med.u-szeged.hu
CR Adegboyega PA, Mifflin RC, DiMari JF, Saada JI, Powell DW, 2002, Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps, and adenomatous colorectal polyps. Arch Pathol Lab Med 126:829–836
Bach SP, Renehan AG, Potten CS, 2000, Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis 3:469–476
Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D, Birchmeier W, 1998, Functional interaction of an axin homolog, conductin, with beta-catenin, APC and GSK3beta. Science 280:596–599
Brachvogel B, Moch H, Pausch F, Schlotzer-Schrehardt U, Hofmann C, Hallmann R, von der Mark K, Winkler T, Poschl E, 2005, Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell-like population with the capacity to differentiate into multiple mesenchymal lineages. Development 132:2657–2668
De Vriese S, Tilton RG, Mortier S, Lameire NH, 2006, Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia. Nephrol Dial Transplant 21:2549–2555
Hermiston ML, Wong MH, Gordon JI, 1996, Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system. Genes Develop 10:985–996
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Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB, 1999, Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 277:C1–C19
Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB, 1999, Myofibroblasts. II. Intestinal subepithelial myofibroblasts. Am J Physiol 277:C183–C201
Powell DW, Adegboyega PA, DiMari JF, Mifflin RC, 2005, Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol Gastrointest Liver Physiol 289:G2–G7
Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM, 2002, Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res 62:6846–6849
Tsujii M, DuBois RN, 1995, Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthases-2. Cell 83:493–501
Valentich JD, Popov V, Saada JI, Powell DW, 1997, Phenotypic characterization of an intestinal subepithelial myofibroblast cell line. Am J Physiol 272:C1513–C1524
Vyas SK, Leyland H, Gentry J, Arthur MJ, 1995, Rat hepatic lipocytes synthesize and secrete transin, stromelysin, in early primary culture. Gastroenterology 109:889–898
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 391
EP 396
DI 10.1007/s12253-011-9457-9
PG 6
ER
PT J
AU Liao, M
Tong, P
Zhao, J
Zhang, Y
Li, Z
Wang, J
Feng, X
Hu, M
Pan, Y
AF Liao, Mingmei
Tong, Ping
Zhao, Jinfeng
Zhang, Yangde
Li, Zhehai
Wang, Jiwei
Feng, Xueping
Hu, Man
Pan, Yifeng
TI Prognostic Value of Matrix Metalloproteinase-1/ Proteinase-Activated Receptor-1 Signaling Axis in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Matrix metalloproteinase-1; Proteinase-activated receptor-1; Prognosis
ID Hepatocellular carcinoma; Matrix metalloproteinase-1; Proteinase-activated receptor-1; Prognosis
AB Matrix metalloproteinase-1 (MMP-1) is proposed to be involved in both tumor cell invasion and metastasis. MMP-1 proteolytically activates protease activated receptor-1 (PAR-1), which also plays an important role in tumor development and progression. However, it is currently unknown whether MMP-1 activation of PAR-1 has relevance to the progression of hepatocellular carcinoma (HCC). To address this problem, we investigate the clinicopathological and prognostic value of MMP-1/PAR-1 signaling axis in HCC. Immunohistochemistry assay was used to determine the expression of MMP-1 and PAR-1 proteins in normal and HCC tissues. The correlations of MMP-1 and PAR-1 expression with clinicopathological parameters were assessed by Chisquared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors.MMP-1 and PAR-1 immunoreactivities were negative or low in normal liver tissues, but high in HCC tissues. PAR-1 expression was significantly correlated with that of MMP-1 (r=0.896, p<0.0001). The overexpression of MMP-1 and PAR-1 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high MMP-1 and PAR-1 expression had significantly poorer overall survival (OS) (both P<0.001) and disease-free survival (DFS) (both P<0.001) when compared with patients with the low expression of MMP-1 and PAR-1. On multivariate analysis, MMP-1 and PAR-1 expression patterns were found to be independent prognostic factors for OS (both P<0.001) and DFS (both P<0.001). Our results suggest for the first time that the MMP-1/PAR-1 signaling axis might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with HCC.
C1 [Liao, Mingmei] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
[Tong, Ping] Central South University, State Key Laboratory of Medical GeneticsChangsha, Hunan, China.
[Zhao, Jinfeng] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
[Zhang, Yangde] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
[Li, Zhehai] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
[Wang, Jiwei] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
[Feng, Xueping] Central South University, Xiangya Hospital, 410008 Changsha, Hunan, China.
[Hu, Man] Central South University, Xiangya Hospital, 410008 Changsha, Hunan, China.
[Pan, Yifeng] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan, China.
RP Pan, Y (reprint author), Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, China.
EM yifengp@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 397
EP 403
DI 10.1007/s12253-011-9458-8
PG 7
ER
PT J
AU Rajalingam, K
Sugunadevi, G
Arokia Vijayaanand, M
Kalaimathi, J
Suresh, K
AF Rajalingam, Kasinathan
Sugunadevi, Govindasamy
Arokia Vijayaanand, Mariadoss
Kalaimathi, Janakiraman
Suresh, Kathiresan
TI Anti-Tumour and Anti-Oxidative Potential of Diosgenin against 7, 12-Dimethylbenz(a)anthracene Induced Experimental Oral Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Antioxidants; Lipid peroxidation; Diosgenin; DMBA; Histopathology
ID Antioxidants; Lipid peroxidation; Diosgenin; DMBA; Histopathology
AB The ultimate aim of the present study was to exploring the chemopreventive efficacy of diosgenin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. The chemopreventive potential of diosgenin was evaluated by measuring the tumour incidence, tumour volume and tumour burden as well as analyzing the activities of detoxification agents, levels of lipid peroxidation byproducts and antioxidants status by specific colorimetric methods. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouches of male Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin, thrice a week for 16 weeks. DMBA painted animals were indicating the morphological changes as depicted as hyperplasia, dysplasia and well-developed squamous cell carcinoma. Moreover, antioxidants and lipid peroxidation byproducts levels were drastically altered in DMBA painted hamsters. Oral administration of diosgenin (80 mg/kg bw) to DMBA painted hamsters on alternate days for 16 weeks significantly reduced the formation of oral tumour and normalized the above biochemical abnormalities. We conclude that the diosgenin is probably potent chemopreventive agent due to their antioxidant function in DMBA induced hamster buccal pouch carcinogenesis.
C1 [Rajalingam, Kasinathan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Sugunadevi, Govindasamy] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Arokia Vijayaanand, Mariadoss] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Kalaimathi, Janakiraman] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
[Suresh, Kathiresan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608 002 Tamil Nadu, India.
RP Suresh, K (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
EM suraj_cks@yahoo.co.in
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 405
EP 412
DI 10.1007/s12253-011-9460-1
PG 8
ER
PT J
AU Varga, I
Hutoczki, G
Szemcsak, DCs
Zahuczky, G
Toth, J
Adamecz, Zs
Kenyeres, A
Bognar, L
Hanzely, Z
Klekner,
AF Varga, Imre
Hutoczki, Gabor
Szemcsak, D Csaba
Zahuczky, Gabor
Toth, Judit
Adamecz, Zsolt
Kenyeres, Annamaria
Bognar, Laszlo
Hanzely, Zoltan
Klekner, Almos
TI Brevican, Neurocan, Tenascin-C and Versican are Mainly Responsible for the Invasiveness of Low-Grade Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Astrocytoma; Brain metastasis; Schwannoma; Normal brain; Extracellular matrix; Invasion
ID Astrocytoma; Brain metastasis; Schwannoma; Normal brain; Extracellular matrix; Invasion
AB The extent of tumor removal determines the effectiveness of postoperative oncotherapy. This is especially true for primary brain tumors, where peritumoral invasion usually makes radical resection impossible. The aim of the study was to determinate the specific expression pattern of invasion related molecules of different intracranial tumors and to identify molecules that are principally responsible for the peritumoral invasiveness of grade II astrocytoma mRNA expression of 26 extracellular matrix (ECM) molecules was determined in tissue samples from grade II astrocytoma, schwannoma, intracerebral metastases of non-small cell lung cancer and normal brain. Immunohistochemical staining for brevican, neurocan, tenascin-C and versican was also performed for each tumor group. Comparing astrocytoma to metastasis, schwannoma and normal brain; and metastasis and schwannoma to normal brain, 22, 17, 20, 21, and 19 molecules, respectively, were found to be significantly overexpressed at the mRNA level. Cluster analysis of mRNA expression showed a specific gene expression pattern for each histological group. Four molecules of 26 were found to be associated to astrocytoma. Immunohistochemical staining confirmed the results of the mRNA analysis at the protein level. Tumors of different origin have a specific invasive phenotype that can evidently determinate on gene expression level. This characteristic expression pattern of the invasion-related molecules might help to screen exact targets for anti-invasion drugs. In case of low-grade astrocytoma. brevican, neurocan, tenascin-C and versican were found to correlate principally with the invasive phenotype of low-grade astrocytoma, thus these molecules can potentially serve as targets for anti-invasion therapy in the future.
C1 [Varga, Imre] Kenezy Gyula Hospital, Department of PulmonologyDebrecen, Hungary.
[Hutoczki, Gabor] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Szemcsak, D Csaba] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Zahuczky, Gabor] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Toth, Judit] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Adamecz, Zsolt] University of Debrecen, Medical and Health Science Center, Institute of Nuclear MedicineDebrecen, Hungary.
[Kenyeres, Annamaria] University of Medicine, The Institute of Anatomy, Histology and EmbryologyDebrecen, Hungary.
[Bognar, Laszlo] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Hanzely, Zoltan] Orszagos Pszichiatriai es Neurologiai IntezetBudapest, Hungary.
[Klekner, Almos] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
RP Klekner, (reprint author), University of Debrecen, Clinical Center, Department of Neurosurgery, 4032 Debrecen, Hungary.
EM aklekner@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 413
EP 420
DI 10.1007/s12253-011-9461-0
PG 8
ER
PT J
AU Kelemen, Gy
Varga, Z
Lazar, Gy
Thurzo, L
Kahan, Zs
AF Kelemen, Gyongyi
Varga, Zoltan
Lazar, Gyorgy
Thurzo, Laszlo
Kahan, Zsuzsanna
TI Cosmetic Outcome 1–5 Years After Breast Conservative Surgery, Irradiation and Systemic Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast-conserving therapy; Cosmesis; Fibrosis; Radiotherapy dose; Irradiated volume
ID Breast-conserving therapy; Cosmesis; Fibrosis; Radiotherapy dose; Irradiated volume
AB The late side-effects of the local therapy of early breast cancer depend on many patient- and therapy-related parameters.We aimed at investigating the factors that influence the cosmetic and functional outcomes among our breast cancer patients after breast-conserving surgery and conformal radiotherapy, with or without adjuvant systemic therapy. A study was made of the association of the cosmetic outcome after a median follow-up time of 2.4 years and the clinical data on 198 patients extracted from a prospectively compiled database. Breast tenderness occurred more frequently among patients ≤50 years old (p<0.05). Long-term side effects were related to radiotherapy-related factors the most, while no effect of the systemic therapy could be detected. The risk of hyperpigmentation, breast edema and breast fibrosis increased by 18%, 23% and 7%, respectively for every 100 cm3 increase in the irradiated breast volume, while that of breast edema and breast fibrosis increased by 21% and 12%, respectively for every 10 cm3 increase in the boost volume. Patients who received a photon boost were significantly more likely to develop breast edema and fibrosis than those who received electrons (p<0.005). Dose inhomogeneity was related to the volume of the irradiated breast (p=0.037). Dyspigmentation developed more often among patients older than 50 years, while smoking favoured both dyspigmentation and teleangiectasia. Breast edema was related to dyspigmentation (p=0.003), fibrosis (p<0.001) and breast asymmetry (p=0.032), whereas none of these abnormalities were associated with teleangiectasia. Body image changes were more frequent at a younger age (p<0.005), while the need to change clothing habits occurred more often at an older age (p<0.05). Radiotherapy-related parameters appear to exert the greatest effect on the overall cosmetic outcome after breast-conserving surgery and postoperative radiotherapy.
C1 [Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM kahan@onko.szote.u-szeged.hu
CR Voogd AC, Nielsen M, Peterse JL, Blichert-Toft M, Bartelink H, Overgaard M et al, 2001, Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 19:1688– 1697
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER et al, 2002, Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233–1241
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 421
EP 427
DI 10.1007/s12253-011-9462-z
PG 7
ER
PT J
AU Toth, L
Andras, Cs
Molnar, Cs
Tanyi, M
Csiki, Z
Molnar, P
Szanto, J
AF Toth, Laszlo
Andras, Csilla
Molnar, Csaba
Tanyi, Miklos
Csiki, Zoltan
Molnar, Peter
Szanto, Janos
TI Investigation of β-catenin and E-cadherin Expression in Dukes B2 Stage Colorectal Cancer with Tissue Microarray Method. Is It a Marker of Metastatic Potential in Rectal Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE β-catenin and E cadherin; Colorectal cancer; TMA; Metastasis
ID β-catenin and E cadherin; Colorectal cancer; TMA; Metastasis
AB β-catenin and E cadherin are both membraneassociated proteins which are essential regulators and providers of cellular adhesion. In the metastatic cascade of malignant tumours, detachment of tumour cells from each other is a very important step. It has been shown in several tumour types, that reduced expression of these proteins is important. The aim of our study was to clarify the expression profile of these proteins, and correlate the findings with the metastasizing potential of early stage colon and rectal cancers. Formalin fixed and paraffin embedded samples from 79 Dukes B2 stage colorectal cancer were examined using a tissue microarray approach. The expression of β-catenin and E-cadherin proteinswas determined immunohistochemically. Our findings indicated that there is a tendency for metastatic spread in cases when membranous expression of β-catenin is lost (p=0.062). Similarly metastases in negative cases developed more rapidly, than in positive ones (p=0.05). Survival rate was worse in the negative cases. The risk of metastasis in rectal cancer was significantly higher in the β-catenin membranously negative than positive groups (p=0.024) and in case of β-catenin nuclear expression the risk was also higher (p=0.047). Reduced E-cadherin expression also correlated with development of metastatic disease, but this association was statistically not significant. The immunohistochemical analysis of 79 cases shows that in Dukes B2 stage colorectal tumours clarification of β-catenin and E-cadherin expression patterns is reliable for predicting the metastatic potential of early stage rectal cancer and hence the method may have relevant implications in the therapeutic management of these cancers.
C1 [Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Andras, Csilla] University of Debrecen, Department of Oncology, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Molnar, Csaba] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Tanyi, Miklos] University of Debrecen, Department of Surgery and Operative Techniques, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Csiki, Zoltan] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Molnar, Peter] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
[Szanto, Janos] University of Debrecen, Department of Oncology, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
RP Toth, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, 4032 Debrecen, Hungary.
EM tothlasz@dote.hu
CR Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics, 2008. CA Cancer J Clin 58:71–96
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 429
EP 437
DI 10.1007/s12253-011-9463-y
PG 9
ER
PT J
AU Kaira, K
Okumura, T
Nakagawa, K
Ohde, Y
Takahashi, T
Murakami, H
Naito, T
Endo, M
Kondo, H
Nakajima, T
Yamamoto, N
AF Kaira, Kyoichi
Okumura, Takehiro
Nakagawa, Kazuo
Ohde, Yasuhisa
Takahashi, Toshiaki
Murakami, Haruyasu
Naito, Tateaki
Endo, Masahiro
Kondo, Haruhiko
Nakajima, Takashi
Yamamoto, Nobuyuki
TI MUC1 Expression in Pulmonary Metastatic Tumors: A Comparison of Primary Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MUC1; Pulmonary metastatic tumor; NSCLC; 18F-FDG PET; Glut1; Hypoxia
ID MUC1; Pulmonary metastatic tumor; NSCLC; 18F-FDG PET; Glut1; Hypoxia
AB MUC1 expression has been described as a predictor for tumor progression and worsening of prognosis in various human neoplasms. However, little is known about the role of MUC1 expression in pulmonary metastatic tumors. The aim of this study is to examine the clinicopathological significance of MUC1 expression in pulmonary metastatic tumors (PMT). One hundred forty-seven patients with PMT who underwent 18F-FDG PET before metastasectomy were included in this study. Tumor sections were stained by immunohistochemistry for MUC1, glucose transporter 1 (Glut1), hypoxia-inducible-1α (HIF-1α) and vascular endothelial growth factor (VEGF). 18F-FDG uptake and the expression of these biomarkers were correlated in primary lung cancer. MUC1 expression pattern was classified into high-grade polarized expression (HP), low-grade polarized expression (LP), or depolarized expression (DP) group. Of 147 patients, HP, LP and DP group were 9 (6%), 114 (78%) and 24 (16%), respectively. The expression of Glut1, HIF-1αand VEGF, and 18F-FDG uptake were significantly higher in DP group than HP or LP groups. MUC1 expression with HP and DP pattern was significantly higher in primary lung cancer than in PMT, whereas, MUC1 expression with LP pattern yielded a significantly high positive rate in PMT. LP group was recognized in the majority of patients with pulmonary metastatic adenocarcinoma, especially colon cancer, whereas, HP group was significantly low in pulmonary metastatic adenocarcinoma as compared with primary adenocarcinoma. Polarized MUC1 has a different expression pattern between primary and metastatic tumors with adenocarcinoma, and depolarized MUC1 is closely associated with glucose metabolism and hypoxia.
C1 [Kaira, Kyoichi] Shizuoka Cancer Center, Division of Thoracic Oncology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Okumura, Takehiro] Shizuoka Cancer Center, Division of Thoracic Surgery, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Nakagawa, Kazuo] Shizuoka Cancer Center, Division of Thoracic Surgery, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Ohde, Yasuhisa] Shizuoka Cancer Center, Division of Thoracic Surgery, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Takahashi, Toshiaki] Shizuoka Cancer Center, Division of Thoracic Oncology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Murakami, Haruyasu] Shizuoka Cancer Center, Division of Thoracic Oncology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Naito, Tateaki] Shizuoka Cancer Center, Division of Thoracic Oncology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Endo, Masahiro] Shizuoka Cancer Center, Division of Diagnostic Radiology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Kondo, Haruhiko] Shizuoka Cancer Center, Division of Thoracic Surgery, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Nakajima, Takashi] Shizuoka Cancer Center, Division of Pathology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
[Yamamoto, Nobuyuki] Shizuoka Cancer Center, Division of Thoracic Oncology, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, 411-8777 Shizuoka, Japan.
RP Kaira, K (reprint author), Shizuoka Cancer Center, Division of Thoracic Oncology, 411-8777 Shizuoka, Japan.
EM kkaira1970@yahoo.co.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 439
EP 447
DI 10.1007/s12253-011-9465-9
PG 9
ER
PT J
AU Feher, ZL
Pocsay, G
Krenacs, L
Zvara,
Bagdi, E
Pocsay, R
Lukacs, G
Gyory, F
Gazdag, A
Tarko, E
Puskas, GL
AF Feher, Z Liliana
Pocsay, Gabor
Krenacs, Laszlo
Zvara, Agnes
Bagdi, Eniko
Pocsay, Reka
Lukacs, Geza
Gyory, Ferenc
Gazdag, Andrea
Tarko, Erzsebet
Puskas, G Laszlo
TI Amplification of Thymosin Beta 10 and AKAP13 Genes in Metastatic and Aggressive Papillary Thyroid Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thymosin beta 10 (TB10); Tre-2 oncogene; AKAP13; Genomic amplification; Metastasis; Papillary thyroid carcinoma (PTC)
ID Thymosin beta 10 (TB10); Tre-2 oncogene; AKAP13; Genomic amplification; Metastasis; Papillary thyroid carcinoma (PTC)
AB Papillary thyroid carcinoma (PTC) is the most common well-differentiated thyroid cancer. Although the great majority of the cases exhibit an indolent clinical course, some of them develop local invasion with distant metastasis, and a few cases transform into undifferentiated/anaplastic thyroid carcinoma with a rapidly lethal course. To identify gene copy number alterations predictive of metastatic potential or aggressive transformation, arraybased comparative genomic hybridization (CGH-array) was performed in 43 PTC cases. Formalin-fixed and paraffinembedded samples from primary tumours of 16 cases without metastasis, 14 cases with only regional lymph node metastasis, and 13 cases with distant metastasis, recurrence or extrathyroid extension were analysed. The CGH-array and confirmatory quantitative real-time PCR results identified the deletion of the EIF4EBP3 and TRAK2 gene loci, while amplification of thymosin beta 10 (TB10) and Tre-2 oncogene regions were observed as general markers for PTC. Although there have been several studies implicating TB10 as a specific marker based on gene expression data, our study is the first to report on genomic amplification. Although no significant difference could be detected between the good and bad prognosis cases in the A-kinase anchor protein 13 (AKAP13) gene region, it was discriminative markers for metastasis. Amplification in the AKAP13 region was demonstrated in 42.9% and 15.4% of the cases with local or with distant metastasis, respectively, while no amplification was detected in nonmetastatic cases. AKAP13 and TB10 regions may represent potential new genomic markers for PTC and cancer progression.
C1 [Feher, Z Liliana] University of Szeged, Department of Medical Genetics, 6701 Szeged, Hungary.
[Pocsay, Gabor] Bekes County Pandy Kalman Hospital, Department of Internal MedicineGyula, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Zvara, Agnes] University of Szeged, Department of Medical Genetics, 6701 Szeged, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Pocsay, Reka] Bekes County Pandy Kalman Hospital, Department of Internal MedicineGyula, Hungary.
[Lukacs, Geza] University of Debrecen, Medical and Health Science Centre, 1st Department of SurgeryDebrecen, Hungary.
[Gyory, Ferenc] University of Debrecen, Medical and Health Science Centre, 1st Department of SurgeryDebrecen, Hungary.
[Gazdag, Andrea] Bekes County Pandy Kalman Hospital, Department of Internal MedicineGyula, Hungary.
[Tarko, Erzsebet] Borsod-Abauj-Zemplen County Hospital, 2nd Department of Internal MedicineMiskolc, Hungary.
[Puskas, G Laszlo] University of Szeged, Department of Medical Genetics, 6701 Szeged, Hungary.
RP Puskas, GL (reprint author), University of Szeged, Department of Medical Genetics, 6701 Szeged, Hungary.
EM pusi@brc.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 449
EP 458
DI 10.1007/s12253-011-9467-7
PG 10
ER
PT J
AU El-Gendi, MS
Mostafa, FM
El-Gendi, MA
AF El-Gendi, Mohamed Saba
Mostafa, Farouk Mohamed
El-Gendi, Mohamed Ahmed
TI Stromal Caveolin-1 Expression in Breast Carcinoma. Correlation with Early Tumor Recurrence and Clinical Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; Clinical outcome; Predictive value; Stromal caveolin-1; Tumor recurrence
ID Breast carcinoma; Clinical outcome; Predictive value; Stromal caveolin-1; Tumor recurrence
AB Caveolin- (cav-1) has been linked to tumor progression and clinical outcome in breast cancer, but its role as a prognostic marker is still unclear. We evaluated stromal and tumor caveolin-1 expression in 91 breast carcinomas, and assessed the association between their expression and clinicopathologic variables as well as patient outcome and early tumor recurrence. Absence of stromal caveolin-1 expression was detected in 18.7% of cases, while 25.3% of cases revealed tumor epithelial caveolin-1 expression. Combined stromal and tumor caveolin-1 immunopositivity was seen in 24.2% of cases. Absence of stromal cav-1 associated with larger tumor size, higher grade, higher nodal stage, higher number of positive nodes, higher TNM stage, positive HER2 status, higher recurrence rate, and shorter mean progression free survival (PFS). Stromal cav-1 status was a significant predictor of PFS in ER+, PR +, and HER2 + tumors. In tamoxifentreated patients, absence of stromal Cav-1 was a significant predictor of poor clinical outcome, suggestive of tamoxifen resistance. Conversely, tumor epithelial and combined caveolin-1 expression, didnot associate with patient outcome. In multivariate analysis, only TNM stage independently associated with survival. Loss of stromal caveolin-1 is a novel breast cancer biomarker that can predict early tumor recurrence, short PFS, and tamoxifen- resistance. Thus, its use as a predictive biomarker, especially in lower grade, lower stage, ER+, PR+, HER2+, and tamoxifen treated patients may allow for early interventions with more aggressive therapies. Thus, stromal marker expression and epithelial-stromal cross talk may be critical for tumor progression and metastasis.
C1 [El-Gendi, Mohamed Saba] University of Alexandria, Faculty of Medicine, Department of Pathology, 29 Fawzy Moaaz Street, SmouhaAlexandria, Egypt.
[Mostafa, Farouk Mohamed] Alexandria Faculty of Medicine, Departement of Clinical OncologyAlexandria, Egypt.
[El-Gendi, Mohamed Ahmed] Alexandria University, Medical Research Institute, Department of Experimental and Clinical SurgeryAlexandria, Egypt.
RP El-Gendi, MS (reprint author), University of Alexandria, Faculty of Medicine, Department of Pathology, Alexandria, Egypt.
EM sabagendi@yahoo.com
CR Liedtke C, Kersting C, Burger H et al, 2007, Caveolin-1 expression in benign and malignant lesions of the breast. World J Surg Oncol 5:110., DOI 10.1186/1477-7819-5-110
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 459
EP 469
DI 10.1007/s12253-011-9469-5
PG 11
ER
PT J
AU Gao, Ch
Pang, L
Ren, Ch
Ma, T
AF Gao, Chengcheng
Pang, Liqun
Ren, Chengcheng
Ma, Tianheng
TI Prognostic Value of Raf Kinase Inhibitor Protein in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Raf kinase inhibitor protein; Prognosis
ID Esophageal squamous cell carcinoma; Raf kinase inhibitor protein; Prognosis
AB Raf kinase inhibitory protein (RKIP, also PEBP1) is involved in regulation of multiple cellular signaling processes and suppressing metastasis in animal models. Downregulation of RKIP expression has been shown to promote tumor progression in a variety of human cancers. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the prognostic significance of RKIP expression by immunohistochemistry in a group of patients with ESCC treated with surgical resection. RKIP expression in 233 surgically resected ESCC specimens and 49 cases of adjacent normal tissues was detected by using immunohistochemical staining. The clinical and prognostic significance of RKIP expression was statistically analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. Significant downregulation was noted for RKIP protein in ESCCs, compared to adjacent normal tissues (p<0.001). A lower disease-free survival and overall survival of ESCC was found in patients whose tissues had low RKIP expression (both P<0.001). In addition, RKIP expression could stratify the patient survival (disease-free survival / overall survival) in stage II (P=0.01 and 0.02, repectively). The Cox proportionate hazard regression model also established that low expression of RKIP was significantly correlated with increased risk (RR=3.572) of recurrence compared with high RKIP expression (P<0.001). Furthermore, the results of multivariate analysis suggested that RKIP expression (P<0.001) was an independent factor that affected overall survival. These findings suggest that the low expression of RKIP be associated with poor survival in resectable ESCC patients.
C1 [Gao, Chengcheng] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, Jiangsu, China.
[Pang, Liqun] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, Jiangsu, China.
[Ren, Chengcheng] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, Jiangsu, China.
[Ma, Tianheng] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, Jiangsu, China.
RP Ren, Ch (reprint author), Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, China.
EM gao.jsha@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 471
EP 477
DI 10.1007/s12253-011-9470-z
PG 7
ER
PT J
AU Kosmaczewska, A
Bocko, D
Ciszak, L
Wlodarska-Polinska, I
Kornafel, J
Szteblich, A
Masternak, A
Frydecka, I
AF Kosmaczewska, Agata
Bocko, Dorota
Ciszak, Lidia
Wlodarska-Polinska, Iwona
Kornafel, Jan
Szteblich, Aleksandra
Masternak, Anna
Frydecka, Irena
TI Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD28; CTLA-4; T cell; Cervical cancer; Progression; Systemic immunosuppression
ID CD28; CTLA-4; T cell; Cervical cancer; Progression; Systemic immunosuppression
AB Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4+CD28+ and CD8+CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.
C1 [Kosmaczewska, Agata] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, R. Weigla 12, 53-114 Wroclaw, Poland.
[Bocko, Dorota] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, R. Weigla 12, 53-114 Wroclaw, Poland.
[Ciszak, Lidia] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, R. Weigla 12, 53-114 Wroclaw, Poland.
[Wlodarska-Polinska, Iwona] Wroclaw Medical University, Department of Gynecological OncologyWroclaw, Poland.
[Kornafel, Jan] Wroclaw Medical University, Department of Gynecological OncologyWroclaw, Poland.
[Szteblich, Aleksandra] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, R. Weigla 12, 53-114 Wroclaw, Poland.
[Masternak, Anna] Regional Hospital in Opole, Department of HematologyOpole, Poland.
[Frydecka, Irena] Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, R. Weigla 12, 53-114 Wroclaw, Poland.
RP Kosmaczewska, A (reprint author), Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, 53-114 Wroclaw, Poland.
EM kosmacz@iitd.pan.wroc.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 479
EP 489
DI 10.1007/s12253-011-9471-y
PG 11
ER
PT J
AU Luo, D
Huang, H
Lu, ML
Zhao, GF
Chang, J
Zheng, MY
Wang, Y
AF Luo, Deng
Huang, Hua
Lu, Ming-Liang
Zhao, Gong-Fang
Chang, Jiang
Zheng, Meng-Yao
Wang, Yan
TI Abnormal Expression of Adhesion Protein Bves is Associated with Gastric Cancer Progression and Poor Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Bves; Cell adhesion molecules; Metastasis; Prognosis
ID Gastric cancer; Bves; Cell adhesion molecules; Metastasis; Prognosis
AB Although many molecular and biological studies have shown risk factors for gastric cancer, the available knowledge is still insufficient to unveil the exact mechanism of gastric cancer. To investigate the relationships between Bves expression and the clinicopathologic features of gastric cancer and whether Bves can act as prognostic indicators in gastric cancer. Tissues were obtained from the gastrectomy specimens of 306 human gastric cancer and 78 noncancerous gastric tissue at the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University from February 1996 to March 2007. The method of immunohistochemistry was used to investigate the expression of Bves in them. The relationship between Bves expression and the survival times of the patients was retrospectively analysed. Reduced expression of Bves frequently occurred in gastric cancer tissue. Low expression of Bves correlated with histologic differentiation, depth of invasion, regional lymph nodes and distant metastasis, and TNM stages (P<0.05). Bves expression did not correlate with age, gender, location of tumor, size of tumor and histologic type (P>0.05); Further multivariate analysis revealed that lymph node metastasis (P<0.0001), distant metastasis (P<0.0001), surgical treatment (P<0.0001), and the expression of Bves (P<0.0001) were independent prognostic factors in patients with gastric cancer; The Kaplan-Meier plot showed that survival times of patients with low Bves expression was significantly lower than those in patients with high Bves expression. Besides, low Bves expression had a much more significant effect on the survival of those patients with early stage tumors (χ2=131.216,P<0.0001), highlighted by a >51.3% reduction in 3-year survival compared with that of patients with high Bves expression. In late stages, the difference was also significant (χ2=5.818,P=0.016), with a 34.8% reduction in 3-year survival. Reduced expression of Bves in gastric cancer is associated with tumor progression and the patient’s poor survival. This study showed that the studied protein has further provided a basis for the development of potential biomarker for gastric cancer prognosis.
C1 [Luo, Deng] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Huang, Hua] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Lu, Ming-Liang] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Zhao, Gong-Fang] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Chang, Jiang] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Zheng, Meng-Yao] the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, No. 1, MaYuan Road, XiShan District, 650101 Kunming, Yunnan Province, China.
[Wang, Yan] the Second Affiliated Hospital of Kunming Medical University, Department of PathologyKunming, Yunnan Province, China.
RP Huang, H (reprint author), the Second Affiliated Hospital of Kunming Medical University, Department of Gastroenterology, 650101 Kunming, China.
EM 122068863@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 491
EP 497
DI 10.1007/s12253-011-9472-x
PG 7
ER
PT J
AU Ribeiro, MA
Pereira, S
Andrade, S
Costa, M
Lopes, C
Aguas, PA
Monteiro, PM
AF Ribeiro, M Andreia
Pereira, Sofia
Andrade, Sara
Costa, Madalena
Lopes, Carlos
Aguas, P Artur
Monteiro, P Mariana
TI Insulin Prevents Leptin Inhibition of RM1 Prostate Cancer Cell Growth
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Obesity; Leptin; Insulin; RM1 cells; Cellular proliferation
ID Prostate cancer; Obesity; Leptin; Insulin; RM1 cells; Cellular proliferation
AB The association between obesity and cancer is controversial: whereas several epidemiological, clinical and research studies using cancer cell lines have supported that high levels of insulin and leptin could favor prostate cancer development and dissemination, other studies have demonstrated opposite effects or even absence of association. The main goal of this study was to evaluate the in vitro proliferation of murine androgen insensitive prostate carcinoma cells RM1 in the presence of leptin and insulin. After assessing and confirming the presence of leptin and insulin receptors in RM1 cells by immunocytochemistry, cells were cultured in the presence of different concentrations of leptin (0, 25, 50, 100 and 200 ng/mL), insulin (0, 50, 100, 150 and 200 nM) or leptin plus insulin ( 25 ng/ml+50 nM; 50 ng/ml+100 nM; 100 ng/ml+150 nM; 200 ng/ml+200 nM; 25 ng/ml+150 nM; 100 ng/ml+50 nM of leptin plus insulin, respectively). Cell proliferation was evaluated by assessing the percentage of resazurin reduction, a surrogate marker of cell metabolic rate. Leptin significantly decreased the percentage of resazurin reduction in all studied concentrations while there was only a slight or non significant difference in RM1cell proliferation in the presence of insulin or insulin combined with leptin when compared with control. These results show that leptin decreases RM1 prostate cancer cell proliferation at the studied concentrations, while insulin is able to antagonize the leptin inhibition of RM1 prostate cancer cell growth in vitro. The difference in cell growth that is modulated by the various hormonal environments may explain the heterogeneous behavior of prostate cancer in the obese human population.
C1 [Ribeiro, M Andreia] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
[Pereira, Sofia] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
[Andrade, Sara] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
[Costa, Madalena] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
[Lopes, Carlos] University of Porto, Department of Pathology and Immunology of ICBAS, 4099-003 Porto, Portugal.
[Aguas, P Artur] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
[Monteiro, P Mariana] University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
RP Monteiro, PM (reprint author), University of Porto, Clinical and Experimental Endocrinology, Department of Anatomy, 4099-003 Porto, Portugal.
EM mpmonteiro@icbas.up.pt
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 499
EP 507
DI 10.1007/s12253-011-9473-9
PG 9
ER
PT J
AU Hasby, AE
AF Hasby, Adel Eiman
TI Weapons Ovarian Epithelial Tumors May Use in Immune Escape: An Immunohistochemical Correlational Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FasL; Survivin; CD3+ T-lymphocytes; Ovarian epithelial tumors; Immune escape
ID FasL; Survivin; CD3+ T-lymphocytes; Ovarian epithelial tumors; Immune escape
AB Investigate FasL and survivin expression in a series of primary ovarian surface epithelial tumors, correlate their expression with each other, and characterize the presence of CD3+ T-lymphocytes in studied tumors and determine whether their presence correlates with FasL or survivin expression in malignant cases. FasL and survivin expression was assessed in 54 ovarian epithelial tumors. The results were compared between different tumor types and grades. Correlation between both markers’ expression in all studied tumors was done. Either marker’s expression was compared to the mean CD3+ T-lymphocytes per HPF in the studied malignant tumors. Either FasL or survivin expression was significantly higher in malignant versus benign ovarian epithelial tumors (p<0.001 for both) and both markers were strongly correlated to each other (r=0.877 & p<0.001). Malignant tumors show significantly higher mean CD3+ T-lymphocytes than benign and borderline tumors. The mean CD3+ T-lymphocytes decrease significantly on increasing malignant tumor grade (p=0.019) and expression of both FasL and survivin (r=−0.729, -0.582, respectively & p<0.001 for both). The higher expression of FasL and survivin in malignant as compared to benign ovarian tumors suggest that they have a significant role in pathogenesis of ovarian carcinoma. Both markers are strongly correlated to each other and may contribute to immune escape of ovarian carcinoma as their higher expression is associated with decreased number of CD3+T-lymphocytes.
C1 [Hasby, Adel Eiman] Tanta University, Faculty of Medicine, Department of PathologyTanta, Ghrbia, Egypt.
RP Hasby, AE (reprint author), Tanta University, Faculty of Medicine, Department of Pathology, Tanta, Egypt.
EM eimanhasby@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 509
EP 518
DI 10.1007/s12253-011-9474-8
PG 10
ER
PT J
AU Mehes, G
Hegyi, K
Csonka, T
Fazakas, F
Kocsis, Zs
Radvanyi, G
Vadnay, I
Bagdi, E
Krenacs, L
AF Mehes, Gabor
Hegyi, Katalin
Csonka, Tamas
Fazakas, Ferenc
Kocsis, Zsolt
Radvanyi, Gaspar
Vadnay, Istvan
Bagdi, Eniko
Krenacs, Laszlo
TI Primary Uterine NK-Cell Lymphoma, Nasal-Type: A Unique Malignancy of a Prominent Cell Type of the Endometrium
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Aggressive lymphoma; Uterine NK-cells; Angiogenesis; EBV; Dissemination
ID Aggressive lymphoma; Uterine NK-cells; Angiogenesis; EBV; Dissemination
AB Natural killer (NK) cells host in the human endometrium with dedicated role in reproductive physiology. Interestingly, malignant transformation of these specialized cells has not been presented thus far. Here we report a primary endometrial NK-cell lymphoma of a 48 year-old patient presenting with irregular bleeding. The endometrial curetting showed a dense lymphomatous infiltrate demonstrating highly infiltrative aggressive features with characteristic angiocentric, partially angiodestructive growth pattern and accompanying focal necroses. The lymphoma cells displayed a CD3ε/CD56/TIA-1/granzyme-B-positive and CD5/CD4/CD8/TCRγδ-negative immunophenotype, proved to be positive for Epstein-Barr virus by EBER in situ hybridization, and revealed no clonal T-cell receptor gene rearrangement. The diagnosis of uterine extranodal NK-cell lymphoma, nasal-type was made. Clinically, the disease was limited to the uterus at diagnosis, but progressed rapidly, and the patient died within 5 months due disseminated lymphoma, irrespective of intensive chemotherapy. Genuine NK-cell lymphomas occurring in the uterus as primary site seem to be rare making the therapeutic decisions extremely complicated.
C1 [Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hegyi, Katalin] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Csonka, Tamas] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Fazakas, Ferenc] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kocsis, Zsolt] Kazincbarcika City Hospital, Department of PathologyKazincbarcika, Hungary.
[Radvanyi, Gaspar] Semmelweis Hospital, Department of HematologyMiskolc, Hungary.
[Vadnay, Istvan] County Hospital of Borsod-Abauj-Zemplen, Department of PathologyMiskolc, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
RP Mehes, G (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, 4032 Debrecen, Hungary.
EM gabor.mehes@dote.hu
CR Chan JKC, Quintanilla-Martinez L, Ferry JA, Peh SC, 2008, Extranodal NK/T-cell lymphoma, nasal type, in: WHO classification of tumours of haemopoietic and lymphoid tissues. IARC, Lyon, pp 285–288
Kim TM, Heo DS, 2009, Extranodal NK/T-cell lymphoma, nasal type: new staging system and treatment strategies. Cancer Sci 100, 12):2242–2248
Au YW, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, SNG I, Vose J, Armitage JO, Liang R, 2009, Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-cell Lymphoma Project. Blood 113(17):3931–3937
Ohshima K, Liu Q, Koga T, Suzumiya J, Kikuchi M, 2002, Classification of cell lineage and anatomical site and prognosis of extranodal T-cell lymphoma—natural killer cell, cytotoxic Tlymphocyte and non NK/CTL types. Virchows Arch 440, 4):425–435
Huang Y, DeReynies A, De Laval L, Ghazi B, Martin-Garcia N, Travert M, Bosq J, Briere J, Petit B, Thomas E, Coppo P, Marafioti T, Emile JF, Delfau-Laure MH, Schmitt C, Gaulard P, 2010, Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasaltype. Blood 115(6):1226–1237
Kohrt H, Advani R, 2009, Extranodal natural killer/T-cell lymphoma: current concepts in biology and treatment. Leuk Lymphoma 50(11):1773–1784
Briese J, Noack F, Harland A, Horny HP, 2006, Primary extranodal NK/T cell lymphoma, nasal type, of the endometrium: report of an unusual case diagnosed at autopsy. Gynecol Obstet Invest 61(3):164–166
Mhawech P, Medeiros LJ, Bueso-Ramos C, Coffey DM, Gei AF, Shahab I, 2000, Natural killer-cell lymphoma involving the gynecologic tract. Arch Pathol Lab Med 124(10):1510–1513
Nakamura S, Kato M, Ichimura K, Yatabe Y, Kagami Y, Suzuki R, Taji H, Kondo E, Asakura S, Kojima M, Murakami S, Yamao K, Tsuzuki T, Adachi GK, Miwa A, Yoshidai T, 2001, Peripheral T/naural killer-cell lymphoma involving the female genital tract: a clinicopathologic study of 5 cases. Int J Hematol 73(1):108–114
Kim TM, Park YH, Lee SY, Kim JH, Kim DW, Im SA, Kim TY, Kim CW, Heo DS, Bang YJ, Chang KH, Kim NK, 2005, Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)/II(E, extranodal NK/T-cell lymphoma, nasal type. Blood 106(12):3785–3790
Manaster I, Mandelboim O, 2010, The unique properties of uterine NK-cells. Am J Reprod Immunol 63(6):434–444
Kalkunte S, Chichester CO, Gotsch F, Sentman CL, Romero R, Sharma S, 2008, Evolution of non-cytotoxic uterine natural killer cells. Am J Reprod Immunol 59(5):425–432
van den Heuvel M, Peralta C, Bashar S, Taylor S, Horrocks J, Cray BA, 2005, Trafficking of peripheral blood CD56(bright, cells to the decidualizing uterus—new tricks for old dogmas. J Reprod Immunol 67(1–2):21–34
van den Heuvel M, Chantakru S, Xuemei X, Evans SS, Tekpetey F, Mote PA, Clarke CL, Croy BA, 2005, Trafficking of circulating pro-NK-cells to the decidualizing uterus: regulatory mechanisms in the mouse and human. Immunol Invest 34(3):273–293
Quenby S, Nik H, Innes B, Lash G, Turner M, Drury J, Blumer J, 2009, Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Hum Reprod 24(1):45–54
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 519
EP 522
DI 10.1007/s12253-011-9360-4
PG 4
ER
PT J
AU Giordano, G
D’Adda, T
Bottarelli, L
Lombardi, M
Brigati, F
Berretta, R
Merisio, C
AF Giordano, Giovanna
D’Adda, Tiziana
Bottarelli, Lorena
Lombardi, Mariano
Brigati, Francesca
Berretta, Roberto
Merisio, Carla
TI Two Cases of Low-Grade Endometriod Carcinoma Associated with Undifferentiated Carcinoma of the Uterus (Dedifferentiated Carcinoma): A Molecular Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Endometrial undifferentiated carcinoma; Dedifferentiated carcinoma; Microsatellite Instability; Loss of heterozygosity
ID Endometrial undifferentiated carcinoma; Dedifferentiated carcinoma; Microsatellite Instability; Loss of heterozygosity
AB Dedifferentiated carcinoma (DC) is an uterine neoplasm containing both low-grade endometrioid carcinoma (LGEC) and undifferentiated carcinoma (UC). DC is an aggressive tumour even when the UC component represents only 20% of the entire neoplasm. In this paper, two cases DCs at different stages of development, in 61- and 83-yearold women respectively were reported. In addition, in these uterine malignancies microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in order to explain its aggressive behavior, in both components. Case #1 presented metastases at diagnosis, while case #2 was at a lower stage. LGEC component was invasive in case #1 and intramucous in case #2. In both cases, UC components were characterized by a high degree of instability, in accordance of its aggressive behaviour and its architectural heterogeneity. Further studies with more numerous cases are mandatory to confirm these data.
C1 [Giordano, Giovanna] University of Parma, Institute of Pathology, Viale A. Gramsci, 14, 43100 Parma, Italy.
[D’Adda, Tiziana] University of Parma, Institute of Pathology, Viale A. Gramsci, 14, 43100 Parma, Italy.
[Bottarelli, Lorena] University of Parma, Institute of Pathology, Viale A. Gramsci, 14, 43100 Parma, Italy.
[Lombardi, Mariano] University of Parma, Institute of Pathology, Viale A. Gramsci, 14, 43100 Parma, Italy.
[Brigati, Francesca] University of Parma, Institute of Pathology, Viale A. Gramsci, 14, 43100 Parma, Italy.
[Berretta, Roberto] University of Parma, Ob/Gyn ClinicParma, Italy.
[Merisio, Carla] University of Parma, Ob/Gyn ClinicParma, Italy.
RP Giordano, G (reprint author), University of Parma, Institute of Pathology, 43100 Parma, Italy.
EM giovanna.giordano@unipr.it
CR Silverberg SG, Kurman RJ, Nogales F et al, 2003, Epithelial tumors and related lesions. In: Tavassoli FA, Devilee P, eds, Tumors of the breast and female genital organs: World Health Organization classification of tumours. IARC, Lyon, p 227
Altraulsi B, Malpica A, Deavers MT, Bodurka DC, Broddus R, Silva EG, 2005, Undifferentiated carcinoma of the endometrium. Am J Surg Pathol 29:1316–1321
Silva EG, Deavers MT, Malpica A, 2007, Undifferentiated carcinoma of the endometrium: a review. Pathology 39:134–138
Silva EG, Deavers MT, Bodurka DC et al, 2006, Association of Low-Grade Endometrioid carcinoma of the uterus and ovary with carcinoms: a new type of dedifferentiated carcinoma? Int J Gynecol Pathol 25:52–58
Boland CR, Thibodeau SN, Hamilton SR et al, 1998, A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial pre disposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257
Umar A, Boland CR, Terdiman JP et al, 2004, Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer, Lynch syndrome, and microsatellite instability. J Natl Cancer Inst 96:261–268
D'Adda T, Bottarelli L, Azzoni C et al, 2005, Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Mod Pathol 18:795–805
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Slomovitz BM, Burke TW, Eifel PJ et al, 2003, Uterine papillary serous carcinoma, UPSC): a single institution review of 129 cases. Gynecol Oncol 91:463–469
Sherman ME, Bur ME, Kurman RJ, 1995, p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol 26:1268–1274
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Lagarda H, Catasus L, Arguelles R, Matias-Guiu X, Prat J, 2001, K-ras mutations in endometrial carcinomas with microsatellite instability. J Pathol 193:193–199
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Peltomaki P, Lothe RA, Aaltonen LA et al, 1993, Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res 53:5853–5855
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Wirtz HC, Muller W, Noguchi T et al, 1998, Prognostic value and clinicopathological profile of microsatellite instability in gastric cancer. Clin Cancer Res 4:1749–1754
Duggan BD, Felix JC, Muderspach LI et al, 1994, Microsatellite instability in sporadic endometrial carcinoma. J Natl Cancer Inst 86:1216–1221
Wagner BJ, Presnell SC, 2009, Loss of heterozygosity in basic concepts of molecular pathology. Springer US 2:97–107
Black D, Soslow RA, Levine DA et al, 2006, Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol 24(11):1745–1753
Shia J, Black D, Hummer AJ et al, 2008, Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer. Hum Pathol 39(1):116–125
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 523
EP 528
DI 10.1007/s12253-011-9386-7
PG 6
ER
PT J
AU Dundr, P
Fischerova, D
Povysil, C
Tvrdik, D
Cibula, D
AF Dundr, Pavel
Fischerova, Daniela
Povysil, Ctibor
Tvrdik, Daniel
Cibula, David
TI Primary Synovial Sarcoma of the Uterus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Female genital tract; Immunohistochemistry; RT-PCR; Synovial sarcoma; Uterus
ID Female genital tract; Immunohistochemistry; RT-PCR; Synovial sarcoma; Uterus
AB We report a case of a 52-year-old female with synovial sarcoma of the uterine corpus. Grossly, the partly polypoid tumor involved the endometrium with invasion into the inner half of the myometrium. Histologically, the tumor showed biphasic structure with the predominance of poorly differentiated small to medium sized round to oval cells. These cells showed high nuclear to cytoplasmic ratio and were arranged in diffuse sheets. Other component consisted of larger epitheloid cells with ample eosinophilic cytoplasm arranged in irregular nests. These cells were only present in a small amount. Immunohistochemically, the tumor cells in both components showed the expression of EMA, S-100 protein, CD99, and NSE. RT-PCR analysis showed the presence of SYT-SSX1 fusion transcript. At present, the patient shows no signs of tumor relapse 56 months after the diagnosis. To the best of our knowledge, this is the first report of synovial sarcoma arising in uterus.
C1 [Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Fischerova, Daniela] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
[Povysil, Ctibor] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Tvrdik, Daniel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Cibula, David] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 12800 Prague, Czech Republic.
EM pdundr@seznam.cz
CR Weiss SW, Goldblum J, 2008, Malignant soft tissue tumors of uncertain type. In: Weiss SW, Goldblum JR, eds, Enzinger and Weiss’s soft tissue tumors, 5th edition). Mosby Elsevier, St. Louis, pp 1161–220
Al-DarajiW, Lasota J, Foss R, MiettinenM(2009, Synovial sarcoma involving the head: analysis of 36 cases with predilection to the parotid and temporal regions. Am J Surg Pathol 33:1494–1503
Tvrdik D, Svatosova J, Dundr P, Povysil C, 2005, Molecular Diagnosis of Synovial Sarcoma: Detection of SYT-SSX1/2 Fusion Transcripts by RT-PCR in Paraffin-Embedded Tissue. Med Sci Monit 11:MT1–7
Drozenova J, Povysil C, Tvrdik D, Babjuk M, Hanus T, 2008, Primary synovial sarcoma of the kidney. Cesk Patol 44:20–22
Makhlouf HR, Ahrens W, Agarwal B et al, 2008, Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases. Am J Surg Pathol 32:275–281
Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA, 1996, Translocation, X;18, in primary synovial sarcoma of the lung. Cancer Genet Cytogenet 88:49–52
Wang ZH,Wang XC, Xue M, 2010, Clinicopathologic analysis of 4 cases of primary renal synovial sarcoma. Chin J Cancer 29:212–216
Ambani DS, White B, Kaplan AL, Alberto A, 2006, A case of monophasic synovial sarcoma presenting as a vulvar mass. Gynecol Oncol 100:433–436
Holloway CL, Russell AH, Muto M, Albert M, Viswanathan AN, 2007, Synovial cell sarcoma of the vulva: multimodality treatment incorporating preoperative external-beam radiation, hemivulvectomy, flap reconstruction, interstitial brachytherapy, and chemotherapy. Gynecol Oncol 104:253–256
Mitsuhashi A, Nagai Y, Suzuka K et al, 2007, Primary synovial sarcoma in fallopian tube: case report and literature review. Int J Gynecol Pathol 26:34–37
Nielsen GP, Shaw PA, Rosenberg AE, Dickersin GR, Young RH, Scully RE, 1996, Synovial sarcoma of the vulva: a report of two cases. Mod Pathol 9:970–974
Pelosi G, Luzzatto F, Landoni F et al, 2007, Poorly differentiated synovial sarcoma of the vagina: first reported case with immunohistochemical, molecular and ultrastructural data. Histopathology 50:808–810
Smith CJ, Ferrier AJ, Russell P, Danieletto S, 2005, Primary synovial sarcoma of the ovary: first reported case. Pathology 37:385–387
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Povysil C, 1984, Synovial sarcoma with squamous metaplasia. Ultrastruct Pathol 7:207–213
Kosemehmetoglu K, Vrana JA, Folpe AL, 2009, TLE1 expression is not specific for synovial sarcoma: a whole study of 163 soft tissue and bone neoplasms. Mod Pathol 22:872–878
Krskova L, Sumerauer D, Stejskalova E, Kodet R, 2007, A novel variant of SYT-SSX1 fusion gene in a case of spindle cell synovial sarcoma. Diagn Mol Pathol 16:179–183
Turc-Carel C, Dal Cin P, Limon J et al, 1987, Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981–1985
Guillou L, Benhattar J, Bonichon F et al, 2004, Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 22:4040–4050
ten Heuvel SE, Hoekstra HJ, Bastiaannet E, Suurmeijer AJ, 2009, The classic prognostic factors tumor stage, tumor size, and tumor grade are the strongest predictors of outcome in synovial sarcoma: no role for SSX fusion type or ezrin expression. Appl Immunohistochem Mol Morphol 17:189–195
Michal M, Fanburg-Smith JC, Lasota J, Fetsch JF, Lichy J, Miettinen M, 2006, Minute synovial sarcomas of the hands and feet: a clinicopathologic study of 21 tumors less than 1 cm. Am J Surg Pathol 30:721–726
Singer S, Baldini EH, Demetri GD, Fletcher JA, Corson JM, 1996, Synovial sarcoma: prognostic significance of tumor size, margin of resection, andmitotic activity for survival. J Clin Oncol 14:1201–1208
Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM, 2000, Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 18:3794–3803
Palmerini E, Staals EL, Alberghini M et al, 2009, Synovial sarcoma: retrospective analysis of 250 patients treated at a single institution. Cancer 115:2988–2998
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 529
EP 533
DI 10.1007/s12253-011-9391-x
PG 5
ER
PT J
AU Toth, B
Katona, M
Harsing, J
Szepesi,
Karpati, S
AF Toth, Bela
Katona, Maria
Harsing, Judit
Szepesi, Agota
Karpati, Sarolta
TI Indeterminate Cell Histiocytosis in a Pediatric Patient: Successful Treatment with Thalidomide
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Indeterminate cell histiocytosis; Thalidomide; Pediatric patient; Immunohistochemistry; Electronmicroscopy; Birbeck granules
ID Indeterminate cell histiocytosis; Thalidomide; Pediatric patient; Immunohistochemistry; Electronmicroscopy; Birbeck granules
AB The 15-year-old male patient presented several 2–6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.
C1 [Toth, Bela] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria utca 41, 1085 Budapest, Hungary.
[Katona, Maria] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria utca 41, 1085 Budapest, Hungary.
[Harsing, Judit] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria utca 41, 1085 Budapest, Hungary.
[Szepesi, Agota] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria utca 41, 1085 Budapest, Hungary.
RP Toth, B (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM tothbela@bor.sote.hu
CR Gianotti F, Caputo R, 1985, Histiocytic syndromes: a review. J Am Acad Dermatol 13:383–404
Bolognia JL, Jorizzo JL, Rapini RP, eds,, 2008, Dermatology. Mosby Elsevier, London Edinburgh New York Philadelphia St Louis Sidney Toronto
Ringel E, Moschella S, 1985, Primary histiocytic dermatoses. Arch Dermatol 121:1531–1542
Groopman J, Golde D, 1981, The histiocytic disorders: a pathophysiologic analysis. Ann Intern Med 94:95–107
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Manente L, Cotellessa C, Schmitt I et al, 1997, Indeterminate cell histiocytosis: a rare histiocytic disorder. Am J Dermatopathol 19:276–283
Rodriguez-Jurado R, Vidaurri-de la Cruz H, Duran-Mckinster C et al, 2003, Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient. Arch Pathol Lab Med 127(6):748–751
Burgdorf WHC, Plewig G, Wolff HH, Landthaler M, eds,, 2009, Braun-Falco’s dermatology. Springer, Heidelberg
Breatnach AS, 1963, A new concept of the relation between the Langerhans cell and the melanocyte. J Invest Dermatol 40:279– 281
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Ratzinger G, Burgdorf WH, Metze D et al, 2005, Indeterminate cell histiocytosis: fact or fiction? J Cutan Pathol 32(8):552–560
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Berti E, Gianotti R, Alessi E, 1988, Unusual cutaneous histiocytosis expressing an intermediate immunophenotype between Langerhans cells and dermal macrophages. Arch Dermatol 124:1250–1253
Sidoroff A, Zelger B, Steiner H et al, 1996, Indeterminate cell histiocytosis—a clinicopathological entity with features of both X- and non-X histiocytosis. Br J Dermatol 134:525
Calatayud M, Guell JL, Gris O et al, 2001, Ocular involvement in a case of systemic indeterminate cell hitiocytosis: case report. Cornea 20:769
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Segal GH, Mesa MV, Fishleder AJ et al, 1992, Precursor Langerhans cell histiocytosis. An unusual histiocytic proliferation in a patient with persistent non-Hodgkin lymphoma and terminal acute monocytic leukemia. Cancer 70:547–553
Vener C, Soligo D, Berti E et al, 2007, Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia. Br J Dermatol 156(6):1357–1361
Broekaert SM, Metzler G, Burgdorf W et al, 2007, Multisystem Langerhans cell histiocytosis: successful treatment with thalidomide. Am J Clin Dermatol 8(5):311–314
Wang CH, Chen GS, 2004, Indeterminate cell histiocytosis: a case report. J Med Sci 20:24–30
Malhomme de la Roche H, Lai-Cheong JE, Calonje E et al, 2008, Indeterminate cell histiocytosis responding to total skin electron beam therapy. Br J Dermatol 158(4):838–840
Eichholz A, Merchant S, Gaya AM, 2010, Anti-angiogenesis therapies: their potential in cancer management. Onco Targets Ther 24(3):69–82
Ventura F, Pereira T, da Luz Duarte M et al, 2010, Indeterminate cell histiocytosis in association with acute myeloid leukemia. Dermatol Res Pract 2010:569345. Epub 2010 Jun 21
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 535
EP 538
DI 10.1007/s12253-011-9405-8
PG 4
ER
PT J
AU Mahta, A
Qu, Y
Nastic, D
Sundstrom, M
Kim, YR
Saria, M
Santagata, S
Kesari, S
AF Mahta, Ali
Qu, Yan
Nastic, Denis
Sundstrom, Maria
Kim, Y Ryan
Saria, Marlon
Santagata, Sandro
Kesari, Santosh
TI Relapsing Tumefactive Lesion in an Adult with Medulloblastoma Previously Treated with Chemoradiotherapy and Stem Cell Transplant
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medulloblastoma; Tumefactive; Stem cell transplant; Radiation necrosis
ID Medulloblastoma; Tumefactive; Stem cell transplant; Radiation necrosis
AB Herein, we present an adult case of medulloblastoma who received chemotherapy, radiation therapy and stem cell transplantation, and underwent multiple surgical resections for what were thought to be recurrences; however pathology confirmed a diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a consequence of stem cell transplantation rather than a simple radiation treatment effect.
C1 [Mahta, Ali] University of California, Moores Cancer Center, Department of Neurosciences, 3855 Health Sciences Drive, Suite 3336, La Jolla, 92093-0819 San Diego, CA, USA.
[Qu, Yan] University of California, Moores Cancer Center, Department of Neurosciences, 3855 Health Sciences Drive, Suite 3336, La Jolla, 92093-0819 San Diego, CA, USA.
[Nastic, Denis] Umea University Medical SchoolUmea, Sweden.
[Sundstrom, Maria] Umea University Medical SchoolUmea, Sweden.
[Kim, Y Ryan] University of California, Moores Cancer Center, Department of Neurosciences, 3855 Health Sciences Drive, Suite 3336, La Jolla, 92093-0819 San Diego, CA, USA.
[Saria, Marlon] University of California, Moores Cancer Center, Department of Neurosciences, 3855 Health Sciences Drive, Suite 3336, La Jolla, 92093-0819 San Diego, CA, USA.
[Santagata, Sandro] Brigham and Women’s Hospital, Department of Pathology, Division of Neuropathology, 75 Francis Street, 02115 Boston, MA, USA.
[Kesari, Santosh] University of California, Moores Cancer Center, Department of Neurosciences, 3855 Health Sciences Drive, Suite 3336, La Jolla, 92093-0819 San Diego, CA, USA.
RP Kesari, S (reprint author), University of California, Moores Cancer Center, Department of Neurosciences, 92093-0819 San Diego, USA.
EM skesari@ucsd.edu
CR Schultheiss TE, Kun LE, Ang KK, Stephens LC, 1995, Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 31(5):1093–1112
Armstrong CL, Hunter JV, Ledakis GE et al, 2002, Late cognitive and radiographic changes related to radiotherapy: initial prospective findings. Neurology 59(1):40–48
Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP, 1998, Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? AJNR Am J Neuroradiol 19(3):407–413
Sorensen J, Savitcheva II, Engler H, Langstrom B, 2000, 3. Utility of PET and 11 C-Methionine in the Paediatric Brain Tumors. Clin Positron Imaging 3(4):157
Chao ST, Suh JH, Raja S, Lee SY, Barnett G, 2001, The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96(3):191–197
Giannopoulou C, Fragaki C, 2006, Positron emission tomography in evaluating the response to treatment of brain tumors, lymphomas and breast cancer. Hell J Nucl Med 9(2):117–125
Fouladi M, Chintagumpala M, Laningham FH et al, 2004, White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 22(22):4551–4560
Asato R, Akiyama Y, Ito M et al, 1992, Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate. Cancer 70(7):1997–2004
Paakko E, Vainionpaa L, Lanning M, Laitinen J, Pyhtinen J, 1992, White matter changes in children treated for acute lymphoblastic leukemia. Cancer 70(11):2728–2733
Hertzberg H, Huk WJ, Ueberall MA et al, 1997, CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL–an evaluation of the interferences between morphology and neuropsychological performance. The German Late Effects Working Group. Med Pediatr Oncol 28(6):387–400
Khong PL, Kwong DL, Chan GC et al, 2003, Diffusion-tensor imaging for the detection and quantification of treatment-induced white matter injury in children with medulloblastoma: a pilot study. AJNR Am J Neuroradiol 24(4):734–740
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 539
EP 543
DI 10.1007/s12253-011-9464-x
PG 5
ER
PT J
AU Tornoczky, T
Bogner, B
Krausz, Th
Ottoffy, G
Szuhai, K
AF Tornoczky, Tamas
Bogner, Barna
Krausz, Thomas
Ottoffy, Gabor
Szuhai, Karoly
TI Angiomatoid Fibrous Histiocytoma: Pleomorphic Variant Associated with Multiplication of EWSR1-CREB1 Fusion Gene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AFH; Angiomatoid fibrous histiocytoma; Pleomorphic; Multiplication; EWSR1-CREB1 fusion gene
ID AFH; Angiomatoid fibrous histiocytoma; Pleomorphic; Multiplication; EWSR1-CREB1 fusion gene
AB Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor which exceptionally occurs in visceral organs or bones. Histologically this is a bland, monomorphic tumor and only occasionally shows pleomorphism. Vast majority of the soft tissue cases share the same translocation and the resulting EWSR1-CREB1 gene fusion as background pathogenetic alteration. Here we report a 10-year-old boy with subcutaneous tumor of the right shoulder. Histological, immunohistochemical and FISH analyses of the case revealed pleomorphic phenotype, characteristic immunophenotype and multiplication of the EWSR1-CREB1 fusion gene in the nuclei of the tumor cells. The possible explanation of the fusion gene multiplication, its relation to the morphology and the clinical outcome are discussed in the context of the published literature.
C1 [Tornoczky, Tamas] University of Pecs, Department of Pathology, Rakoczi ut 2, 7623 Pecs, Hungary.
[Bogner, Barna] Balassa Janos County Hospital, Department of PathologySzekszard, Hungary.
[Krausz, Thomas] University of Illinois at Chicago, College of Medicine, Department of PathologyChicago, IL, USA.
[Ottoffy, Gabor] University of Pecs, Department of PediatricsPecs, Hungary.
[Szuhai, Karoly] Leiden University, Medical Center, Department of Molecular Cell BiologyLeiden, The Netherlands.
RP Tornoczky, T (reprint author), University of Pecs, Department of Pathology, 7623 Pecs, Hungary.
EM ttamas64@hotmail.com
CR Enzinger FM, 1979, Angiomatoid malignant fibrous histiocytoma: a distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm. Cancer 44(6):2147–2157
Fletcher CDM, 1991, Angiomatoid “malignant fibrous histiocytoma”: an immunohistochemical study indicative of myoid differentiation. Hum Pathol 22(6):563–568
Fanburg-Smith JC, Miettinen M, 1999, Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Hum Pathol 30, 11):1336–1343
Tanas MR, Rubin BP, Montgomery EA et al, 2010, Utility of FISH in the diagnosis of angiomatoid fibrous histiocytoma: a series of 18 cases. Mod Pathol 23:93–97
Waters BL, Panagopoulos I, Allen EF, 2000, Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF genes induced by a chromosomal translocation involving bands 12q13 and 16p11. Cancer Genet Cytogenet 121:109–116
Hallor KH, Micci F, Meis-Kindblom JM et al, 2007, Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett 251, 1):158–163
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2012
VL 18
IS 2
BP 545
EP 548
DI 10.1007/s12253-011-9468-6
PG 4
ER
PT J
AU Fan, Ch
Yu, J
Liu, Y
Xu, H
Wang, E
AF Fan, Chuifeng
Yu, Juanhan
Liu, Yang
Xu, Hongtao
Wang, Enhua
TI Increased NDRG1 Expression is Associated with Advanced T Stages and Poor Vascularization in Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IHC; MVD; NDRG1; NSCLC; T stage
ID IHC; MVD; NDRG1; NSCLC; T stage
AB N-myc downstream regulated gene 1 (NDRG1) is a member of the N-myc downstream regulated gene family which belongs to the alpha/beta hydrolase superfamily. Earlier studies have shown its association with inhibition of tumor metastasis. However, its function in malignant tumors is not fully enunciated. Recently there was increasing evidence that NDRG1 is involved in stress responses. In the current study, we examined the expression of NDRG1 and its correlation with clinicopathological factors and microvessel density (MVD) in non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC). NDRG1 expression in NSCLC (71/115, 61.7%) was higher than that in normal lung tissues (32/115, 27.8%) (p<0.05). NDRG1 expression in NSCLC cells was found in cytoplasm (63/115, 54.8%), nuclear (24/115, 20.9%) and cell membrane (13/115, 11.3%). NDRG1 expression in NSCLC with advanced T stages (T2-4) (63/84, 75.0%) was significantly higher than that with T1 stage (8/31, 25.8%) (P<0.05). No other clinicopathological factors including lymph node metastasis were found to be associated with NDRG1 expression (p>0.05). Moreover increased NDRG1 expression was associated with lower MVD in NSCLC (P<0.05). MVD in adenocarcinoma (33.4±8.4/HP) was significantly higher than that in squamous cell carcinoma (SCC) (19.3±8.1/HP) (P<0.05). No other clinicopathological factors were associated with MVD in NSCLC (p>0.05). The present findings indicate an increase of NDRG1 expression with the progress of tumour extent which may be due to unbalanced tumor oxygenation on account of poor vascularization in NSCLC.
C1 [Fan, Chuifeng] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
[Yu, Juanhan] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
[Liu, Yang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
[Xu, Hongtao] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
[Wang, Enhua] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
RP Fan, Ch (reprint author), China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110001 Shenyang, China.
EM fanchuifeng@yeah.net
CR Lachat P, Shaw P, Gebhard S et al, 2002, Expression of NDRG1, a differentiation-related gene, in human tissues. Histochem Cell Biol 118:399–408
Taketomi Y, Sugiki T, Saito T et al, 2003, Identification of NDRG1 as an early inducible gene during in vitro maturation of cultured mast cells. Biochem Biophys Res Commun 306:339–346
Wakisaka Y, Furuta A, Masuda K et al, 2003, Cellular distribution of NDRG1 protein in the rat kidney and brain during normal postnatal development. J Histochem Cytochem 51:1515–1525
Rutherford MN, Bayly GR, Matthews BP et al, 2001, The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells. Leukemia 15:362–370
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Zhou D, Salnikow K, Costa M, 1998, Cap43, a novel gene specially induced by Ni2+ compounds. Cancer Res 58:2182–2189
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Zheng Y, Wang LS, Xia L et al, 2009, NDRG1 is down-regulated in the early apoptotic event induced by camptothecin analogs: the potential role in proteolytic activation of PKC delta and apoptosis. Proteomics 9:2064–2075
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 549
EP 556
DI 10.1007/s12253-010-9294-2
PG 8
ER
PT J
AU Kadar, K
Wolf, K
Tabori, J
Karadi, I
Varkonyi, J
AF Kadar, Katalin
Wolf, Krisztina
Tabori, Judit
Karadi, Istvan
Varkonyi, Judit
TI The Albumin and Monoclonal Protein Ratio as Prognostic Marker for Multiple Myeloma in the Era of Novel Agents
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiple myeloma; Prognostic factors; Albumin; M-protein; A/M ratio
ID Multiple myeloma; Prognostic factors; Albumin; M-protein; A/M ratio
AB Multiple myeloma (MM) is a heterogeneous disease group regarding prognosis, clinical course, and response to therapeutic interventions. Numerous prognostic factors have been identified however there was no consensus about the best prognostic indicators or the proper staging systems. In a previous study the A/M ratio containing albumin (A) and monoclonal component (M) emerged as reliable predictor of survival duration in patients treated with conventional chemotherapy. In the current retrospective study authors evaluated the prognostic role of this fraction in the era of novel agents. They assessed the A/M ratio prior treatment in 56 newly diagnosed MM patients from the aspect of the survival time. According to the results the A/M being <1 at the diagnosis indicated significantly poorer prognosis both at the 2 years (p00,01) and at the 5 years (p00,07) survival endpoints. These results proved that A/M ratio remained valuable marker for predicting prognosis in patients treated with proteosome inhibitor and antiangiogenic therapy as well. Authors recommend therefore applying this A/M ratio in further studies for the better pre-treatment stratification.
C1 [Kadar, Katalin] Semmelweis University, Kutvolgyi Clinical Centre, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Wolf, Krisztina] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Tabori, Judit] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Karadi, Istvan] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
[Varkonyi, Judit] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4., 1125 Budapest, Hungary.
RP Kadar, K (reprint author), Semmelweis University, Kutvolgyi Clinical Centre, 1125 Budapest, Hungary.
EM kadarka@kut.sote.hu
CR Rajkumar SV, 2009, Multiple myeloma. Curr Probl Cancer 1:7–64
Kyle RA, 1983, Long-term survival in multiple myeloma. N Engl J Med 308:314–316
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Eleutherakis-Papaiakovou V, Bamias A, Gika D et al, 2007, Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymph 48:337–341
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San Miguel JF, Fonseca R, Greipp PR, 2004, Prognostic factors and classification for multiple myeloma: contribution to clinical management. In: Malpas JS, Bergsagel DE, Kyle RA, Anderson KC, eds, Myeloma: Biology and management, 3rd edn. Saunders, Elsevier Inc, Oxford, pp 189–199
Witzig TE, Gertz MA, Lust JA et al, 1996, Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma. Blood 88:1780–1787
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Greipp PR, San Miguel J, Durie BG et al, 2005, International staging system for multiple myeloma. J Clin Oncol 23:3412–3420
Jacobson JL, Hussein MA, Barlogie B et al, 2003, Southwest Oncology Group. A new staging system for multiple myeloma patients based on the Southwest Oncology Group, SWOG, experience. Br J Haematol 122:441–450
Kumar SK, Mihael JR, Buadi FK et al, 2009, Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy, mSMART, consensus guidelines. Mayo Clin Proc 84(12):1095–1110
Medical Research Working Party on Leukemia in Adults, 1980, Prognostic features on the third MRC myelomatosis trial. Br J Cancer 42:831–840
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Varkonyi J, Bajzik E, Fazakas A et al, 2009, Short or long survival in multiple myeloma. A simple method for determine the prognosis. Pathol Oncol Res 15:383–387
Kaplan EL, Meier P, 1958, Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 557
EP 561
DI 10.1007/s12253-012-9506-z
PG 5
ER
PT J
AU Lichao, S
Liang, P
Chunguang, G
Fang, L
Zhihua, Y
Yuliang, R
AF Lichao, Sun
Liang, Peng
Chunguang, Guo
Fang, Lv
Zhihua, Yang
Yuliang, Ran
TI Overexpression of PTGIS Could Predict Liver Metastasis and is Correlated with Poor Prognosis in Colon Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PTGIS; Colon cancer; Liver metastasis; Prognosis
ID PTGIS; Colon cancer; Liver metastasis; Prognosis
AB The purpose of this study was to evaluate the predictive ability of PTGIS for liver metastasis. Protein expression of PTGIS was analyzed on tissue microarray consisting of 117 CRC cases with liver metastasis (M1) and 104 cases of CRC without liver metastasis at least 5 years after resection of primary CRC (M0) by immunohistochemistry. Expression of PTGIS in 147 of 221 of primary lesions exhibited positive staining. Moreover, the PTGIS expression was significantly higher in CRC-M1 than CRC-M0 group. More importantly, the 87% (20/23) heterochronous metastatic cases showed positive staining for PTGIS. Collecting the primary and liver metastatic tumor samples from the same colon cancer patients, we tested the expression of PTGIS and revealed that the expression level of PTGIS in the hepatic metastases was noticeably higher than in the matched primary colon cancer tissues from the same patient in 9 out of 16 cases examined. Logistic regression analysis indicated that the expression of PTGIS and lymph node involvement were risk factors in colon cancer liver metastasis independent of the other variables. In leave-one-out validation model, the combination of PTGIS and lymph node involvement yielded the 89.7% satisfactory sensitivity and 83% specificity for detection of hepatic metastasis. Kaplan–Meier survival analysis revealed a correlation between higher PTGIS expression levels and shorter overall survival times. In conclusion, our results suggest that PTGIS combined with lymph node involvement may be used as accurate predictors of liver metastasis in colorectal cancer.
C1 [Lichao, Sun] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, No.17 Panjiayuan Nanli, Chaoyang District, 100021 Beijing, China.
[Liang, Peng] China-Japan Friendship Hospital, Institute of Clinical Medical Sciences, 100029 Beijing, China.
[Chunguang, Guo] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), Department of abdominal surgical oncology, 100021 Beijing, China.
[Fang, Lv] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, No.17 Panjiayuan Nanli, Chaoyang District, 100021 Beijing, China.
[Zhihua, Yang] Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, No.17 Panjiayuan Nanli, Chaoyang District, 100021 Beijing, China.
[Yuliang, Ran] Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, No.17 Panjiayuan Nanli, Chaoyang District, 100021 Beijing, China.
RP Yuliang, R (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College, Cancer Institute (Hospital), State Key Laboratory of Molecular Oncology, 100021 Beijing, China.
EM ran_yuliang@yahoo.com.cn
CR Jemal A, Siegel R, Xu J, Ward E, 2010, Cancer statistics, 2010. CA Cancer J Clin 60:277–300
McMillan DC, McArdle CS, 2007, Epidemiology of colorectal liver metastases. Surg Oncol 16:3–5
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Buchanan FG, Chang W, Sheng H, Shao J, Morrow JD, DuBois RN, 2004, Up-regulation of the enzymes involved in prostacyclin synthesis via Ras induces vascular endothelial growth factor. Gastroenterology 127:1391–1400
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 563
EP 569
DI 10.1007/s12253-011-9478-4
PG 7
ER
PT J
AU Xu, Y
Liu, Z
Guo, K
AF Xu, Yuanhong
Liu, Zhe
Guo, Kejian
TI The Effect of JDP2 and ATF2 on the Epithelial-mesenchymal Transition of Human Pancreatic Cancer Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; Epithelial-mesenchymal transition; Jun dimerization protein 2; Activator protein-1
ID Pancreatic cancer; Epithelial-mesenchymal transition; Jun dimerization protein 2; Activator protein-1
AB Pancreatic cancer is a common malignancy with a bleak outcome due to the early occurrence of micrometastases and poor prognosis. The epithelial-mesenchymal transition (EMT) is considered to be related to the invasion and metastasis of a variety of malignant tumors. Currently, there is no research regarding the relationship of pancreatic cancer EMT with Jun dimerization protein 2 (JDP2), an inhibitor of the activator protein-1 (AP-1) family, and activating transcription factor-2 (ATF2), an AP-1-family member. In this study, we used western blot analysis and immunofluorescence to detect the protein expression of the epithelial marker E-cadherin and the mesenchymal marker vimentin in the pancreatic cancer cell line BxPC3, which was transfected with JDP2 and induced by Collagen I. Compared with the negative control, the E-cadherin and vimentin expression levels did not change significantly, whereas E-cadherin expression decreased and vimentin expression increased in the control group transfected with empty plasmid, suggesting that JDP2 inhibits the EMT induced by Collagen I. Additionally, we verified that compared with the negative control, the morphology of the Capan2 cell line induced by TGF-β1 after transfection with ATF2 was significantly changed, as was the mRNA expression of E-cadherin, whereas the mRNA expression of vimentin, Snail, and ATF2 was significantly increased. Cell invasiveness was also significantly increased (P<0.01), suggesting that ATF2, together with TGF-β1, induced EMT in the Capan2 cell line. The members of the AP-1 family are closely related to EMT and that JDP2, as an AP-1-family inhibitor, inhibits EMT, which could lead to a new direction in molecular-targeted therapy for pancreatic cancer.
C1 [Xu, Yuanhong] First Hospital of China Medical University, Department of Pancreatic Gastroenterologic Surgery, No. 92, Nanjing Rd, 110001 Shenyang, China.
[Liu, Zhe] First Hospital of China Medical University, Department of Pancreatic Gastroenterologic Surgery, No. 92, Nanjing Rd, 110001 Shenyang, China.
[Guo, Kejian] First Hospital of China Medical University, Department of Pancreatic Gastroenterologic Surgery, No. 92, Nanjing Rd, 110001 Shenyang, China.
RP Xu, Y (reprint author), First Hospital of China Medical University, Department of Pancreatic Gastroenterologic Surgery, 110001 Shenyang, China.
EM xuyhsy@yeah.net
CR Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ, Cancer statistics, 2006, CA Cancer J Clin 56:106–30
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Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A, 2006, Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 174:175–83
Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A, 2008, HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem 283:33437–46
Davies M, Robinson M, Smith E, Huntley S, Prime S, Paterson I, 2005, Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem 95:918–31
Nishioka R, Itoh S, Gui T, Gai Z, Oikawa K, Kawai M, Tani M, Yamaue H, Muragaki Y, 2010, SNAIL induces epithelial-tomesenchymal transition in a human pancreatic cancer cell line, BxPC3, and promotes distant metastasis and invasiveness in vivo. Exp Mol Pathol 89:149–57
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Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, Rimm DL, 2003, Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res 63:8103–7
Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H, Zoumpourlis V, 2004, Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors. Cancer Res 64:8573–84
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 571
EP 577
DI 10.1007/s12253-011-9476-6
PG 7
ER
PT J
AU Racz, G
Csenki, Zs
Kovacs, R
Hegyi,
Baska, F
Sujbert, L
Zsakovics, I
Kis, R
Gustafson, R
Urbanyi, B
Szende, B
AF Racz, Gergely
Csenki, Zsolt
Kovacs, Robert
Hegyi, Arpad
Baska, Ferenc
Sujbert, Laszlo
Zsakovics, Ivett
Kis, Renata
Gustafson, Ryan
Urbanyi, Bela
Szende, Bela
TI Subacute Toxicity Assessment of Water Disinfection Byproducts on Zebrafish
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 4-ethylbenzaldehyde; 2; 4-difluoroaniline; Zebrafish; Water disinfection byproducts
ID 4-ethylbenzaldehyde; 2; 4-difluoroaniline; Zebrafish; Water disinfection byproducts
AB Disinfection of raw water is essential to the production of drinking water. However, by-products of disinfection may exert toxic effects. The potential toxic effects of two of these compounds, 4-ethylbenzaldehyde (EBA) and 2,4-difluoroaniline (DFA) were investigated using the zebrafish (Danio rerio) model. The two compounds, dissolved, were introduced in duplicate aquariums containing zebrafish in two different concentrations based on LC50 values. The aquarium water containing EBA or DFA was changed every 96 h throughout the 3 months of treatment. Behavior of the fish in each replicate was inspected twice daily. In course of treatment with both concentrations, fish exposed to DFA displayed behavior associated with visible anxiety, while EBA treated were lethargic and did not evade capture. Application of both concentrations of each component into the aquarium water resulted in dystrophic lesions in the liver, kidney and skin of the fish while preneoplastic lesions and tumors were not observed.
C1 [Racz, Gergely] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26,, 1085 Budapest, Hungary.
[Csenki, Zsolt] Szent Istvan University, Faculty of Agricultural and Environmental Sciences, Department of Fish CultureGodollo, Hungary.
[Kovacs, Robert] Szent Istvan University, Faculty of Agricultural and Environmental Sciences, Department of Fish CultureGodollo, Hungary.
[Hegyi, Arpad] Szent Istvan University, Faculty of Agricultural and Environmental Sciences, Department of Fish CultureGodollo, Hungary.
[Baska, Ferenc] Szent Istvan University, Faculty of Veterinary Medicine, Department of Pathology and Forensic Veterinary Medicine, 1078 Budapest, Hungary.
[Sujbert, Laszlo] Semmelweis University, Department of Public Health, Nagyvarad ter 4, 1089 Budapest, Hungary.
[Zsakovics, Ivett] 3D HISTECH Kft, Konkoly-Thege ut 29-33, 1121 Budapest, Hungary.
[Kis, Renata] 3D HISTECH Kft, Konkoly-Thege ut 29-33, 1121 Budapest, Hungary.
[Gustafson, Ryan] University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Department of Environmental Sciences & EngineeringChapel Hill, NC, USA.
[Urbanyi, Bela] Szent Istvan University, Faculty of Agricultural and Environmental Sciences, Department of Fish CultureGodollo, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26,, 1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Nieuwenhuijsen MJ, Toledano MB, Elliott P, 2000, Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies. J Expo Anal Environ Epidemiol 10:586–599
Cognet L, Courtois Y, Mallevialle J, 1986, Mutagenic activity of disinfection by-products. Environ Health Perspect 69:165–175
Woodruff NWet al, 2001, Human cell mutagenicity of chlorinated and unchlorinated water and the disinfection byproduct 3-chloro-4-, dichloromethyl)-5-hydroxy-2(5H)-furanone, MX). Mutat Res 495:157–168
Morris RD et al, 1992, Chlorination, chlorination by-products, and cancer: a meta-analysis. Am J Public Health 82:955–963
Bove GE Jr, Rogerson PA, Vena JE, 2007, Case control study of the geographic variability of exposure to disinfectant byproducts and risk for rectal cancer. Int J Health Geogr 6:18
Villanueva CM et al, 2007, Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools. Am J Epidemiol 165:148–156
Sujbert L et al, 2006, Genotoxic potential of by-products in drinking water in relation to water disinfection: survey of preozonated and post-chlorinated drinking water by Ames-test. Toxicology 219:106–112
Racz G et al, 2004, Rapid communication: water disinfection byproducts enhanced apoptotic activity in human lymphocytes. J Toxicol Environ Health A 67:1315–1319
Krasner SW et al, 2006, Occurrence of a new generation of disinfection byproducts. Environ Sci Technol 40:7175–7185
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Khudoley VV, 1984, Use of aquarium fish, Danio rerio and Poecilia reticulata, as test species for evaluation of nitrosamine carcinogenicity. Natl Canc Inst Monogr 65:65–70
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 579
EP 584
DI 10.1007/s12253-011-9479-3
PG 6
ER
PT J
AU Chiang, Y
Zhou, X
Wang, Z
Song, Y
Liu, Z
Zhao, F
Zhu, J
Xu, H
AF Chiang, Yeunpo
Zhou, Xin
Wang, Zhenning
Song, Yongxi
Liu, Zhuangkai
Zhao, Fang
Zhu, Jinliang
Xu, Huimian
TI Expression Levels of MicroRNA-192 and -215 in Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clinicopathological characteristics; Gastric cancer; microRNA; miR-192; miR-215
ID Clinicopathological characteristics; Gastric cancer; microRNA; miR-192; miR-215
AB MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. miR-192 and -215, which have the same "seed region", have not been comprehensively investigated using a large number of cases in gastric cancer. The total RNA was extracted from 118 gastric cancer tissues and three gastric cancer cell lines as well as matched non-tumor adjacent tissues (NATs). After polyadenylation and reverse transcription, expression levels of miR-192 and -215 were determined by real-time PCR and calculation using the 2-ΔΔCT method for evaluation of the association between miR-192, and -215 expression levels and clinicopathological characteristics. There were no significant differences in miR-192 and -215 expression levels between gastric cancer tissues and non-tumor counterparts (both p>0.05, paired ttest). Interestingly, miR-192 and -215 were down-regulated in MGC-803 cells, BGC-823 cells and SGC-7901 cells (all p<0.01, paired t-test). Also, the down-regulation of miR-192 and -215 was demonstrated to be associated with increased tumor sizes (both p00.003, Mann–Whitney U test) and advanced Borrmann type tumors (p00.015 and p00.044, respectively, Kruskal-Wallis H test). Moreover, the expression of miR-192 was significantly lower in the pT4 stage of gastric cancer than in pT1, pT2 and pT3 stages (p00.026). Furthermore, there was a strong correlation between miR-192 and -215 in gastric cancer tissues (p<0.001, Pearson regressions). miR-192 and -215 might be related to the proliferation and invasion of gastric cancer. Potentially, they could become important biomarkers.
C1 [Chiang, Yeunpo] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
[Zhou, Xin] ShengJing Hospital of China Medical University, Department of Gynecology and ObstetricsShenyang, China.
[Wang, Zhenning] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
[Song, Yongxi] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
[Liu, Zhuangkai] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
[Zhao, Fang] ShengJing Hospital of China Medical University, Department of Gynecology and ObstetricsShenyang, China.
[Zhu, Jinliang] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
[Xu, Huimian] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
RP Wang, Z (reprint author), China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
EM josieon826@yahoo.com.cn
CR Bartel DP, 2004, MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 585
EP 591
DI 10.1007/s12253-011-9480-x
PG 7
ER
PT J
AU Tokes, AM
Szasz, MA
Juhasz,
Schaff, Zs
Harsanyi, L
Molnar, AI
Baranyai, Zs
Besznyak, I
Zarand, A
Salamon, F
Kulka, J
AF Tokes, Anna-Maria
Szasz, Marcell Attila
Juhasz, Eva
Schaff, Zsuzsa
Harsanyi, Laszlo
Molnar, Arthur Istvan
Baranyai, Zsolt
Besznyak, Istvan
Zarand, Attila
Salamon, Ferenc
Kulka, Janina
TI Expression of Tight Junction Molecules in Breast Carcinomas Analysed by Array PCR and Immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; Tight junction; Claudin; Array; Immunohistochemistry
ID Breast carcinoma; Tight junction; Claudin; Array; Immunohistochemistry
AB In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.
C1 [Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Juhasz, Eva] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Harsanyi, Laszlo] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1091 Budapest, Hungary.
[Molnar, Arthur Istvan] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1091 Budapest, Hungary.
[Baranyai, Zsolt] Fovarosi Onkormanyzat Uzsoki utcai Oktato Korhaz, Sebeszeti-Ersebeszeti Osztaly, Uzsoki u. 29, 1145 Budapest, Hungary.
[Besznyak, Istvan] Fovarosi Onkormanyzat Uzsoki utcai Oktato Korhaz, Sebeszeti-Ersebeszeti Osztaly, Uzsoki u. 29, 1145 Budapest, Hungary.
[Zarand, Attila] Fovarosi Onkormanyzat Uzsoki utcai Oktato Korhaz, Sebeszeti-Ersebeszeti Osztaly, Uzsoki u. 29, 1145 Budapest, Hungary.
[Salamon, Ferenc] Fovarosi Uzsoki utcai Korhaz, Pathologia, Uzsoki u. 29, 1145 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Tokes, AM (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM tokesa1972@yahoo.co.uk
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 593
EP 606
DI 10.1007/s12253-011-9481-9
PG 14
ER
PT J
AU Arvai, K
Nagy, K
Barti-Juhasz, H
Petak, I
Krenacs, T
Micsik, T
Vegso, Gy
Perner, F
Szende, B
AF Arvai, Kristof
Nagy, Katalin
Barti-Juhasz, Helga
Petak, Istvan
Krenacs, Tibor
Micsik, Tamas
Vegso, Gyula
Perner, Ferenc
Szende, Bela
TI Molecular Profiling of Parathyroid Hyperplasia, Adenoma and Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Parathyroid lesions; Apoptosis; Gene expression profiling; Tissue micro array
ID Parathyroid lesions; Apoptosis; Gene expression profiling; Tissue micro array
AB The objective of the study was to examine proliferation and apoptosis associated gene expression in the whole sequence parathyroid lesions to reveal specific features of carcinoma. This study was based on surgically removed parathyroid tissues, gene expression analysis was performed both at gene and protein level. First, mRNA isolation was performed from deep-frozen tissue samples, and further apoptosis pathway-specific cDNA macroarray analysis was carried out. The results were validated with real-time PCR. Subsequently, protein expression was analyzed with immunhistochemistry on TissueMicro Array multi-blocks derived from several paraffinembedded samples. cDNA macroarrays revealed elevated expression of both pro-apoptotic (FAS receptor, TRAIL ligand, CASPASE8, and −4) and anti-apoptotic (cIAP1, APOLLON) genes in benign proliferative lesions compared to that in normal gland. TMA studies showed overexpression of KI67, P53, SURVIVIN and APOLLON protein and failure of expression of P27, BCL2, BAX, CHROMOGRANIN-A, SYNAPTOPHYSIN, CYCLIND1, FLIP, TRAIL, CK8, CK18, CK19 in parathyroid carcinoma was detected. These alterations in gene expression of the investigated products could be used in differentiation between beningn and malignant proliferative processes of the parathyroid gland. Authors conclude that a series of alterations in gene expression such as overexpression of APOLLON, P53, KI67 and suppression of P27, BCL2, BAX lead to uncontrolled cell proliferation, but still not leading to increased apoptotic activity in parathyroid carcinoma.
C1 [Arvai, Kristof] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Nagy, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Barti-Juhasz, Helga] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Petak, Istvan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Vegso, Gyula] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Perner, Ferenc] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Szende, Bela] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Szende, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM bszende@korb1.sote.hu
CR Fernandez-Ranvier GG, Khanafshar E, Jensen K et al, 2007, Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis? Cancer 110(2):255–264
Adami S, Marcocci C, Gatti D. Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res 17 Suppl 2:N18-23
Marx SJ, 2000, Hyperparathyroid and hypoparathyroid disorders. N Engl J Med 343:1863–1875
Fernandez-RanvierGG, Khanafshar E, TachaD et al, 2009, Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer 115(2):334–344
Stojadinovic A, Hoos A, Nissan A et al, 2003, Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol 34(1):54–64
Szende B, Farid P, Vegso G et al, 2004, Apoptosis and P53, Bcl-2 and Bax gene expression in parathyroid glands of patients with hyperparathyroidism. Pathol Oncol Res 10(2): 98–103
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Masi G, Barzon L, Iacobone M et al, 2008, Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer 15(4):1115–1126
Shih RY, Fackler S, Maturo S et al, 2009, Parathyroid carcinoma in multiple endocrine neoplasia type 1 with a classic germline mutation. Endocr Pract 15(6):567–572
Cetani F, Ambrogini E, Viacava P et al, 2007, Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol 156(5):547–554
Howell VM, Gill A, Clarkson A et al, 2009, Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab 94(2):434–441
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 607
EP 614
DI 10.1007/s12253-011-9483-7
PG 8
ER
PT J
AU Helpap, B
Kristiansen, G
Beer, M
Kollermann, J
Oehler, U
Pogrebniak, A
Fellbaum, Ch
AF Helpap, Burkhard
Kristiansen, Glen
Beer, Michaela
Kollermann, Jens
Oehler, Ulrich
Pogrebniak, Alexsei
Fellbaum, Christian
TI Improving the Reproducibility of the Gleason Scores in Small Foci of Prostate Cancer - Suggestion of Diagnostic Criteria for Glandular Fusion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate carcinoma; Glandular fusion; Interobserver reproducibility
ID Prostate carcinoma; Glandular fusion; Interobserver reproducibility
AB High upgrading rates of Gleason score 6 to 7 carcinomas between biopsy and radical prostatectomy specimens may be produced by change of fused glands of pattern 3 to pattern 4. Therefore, inter-observer reproducibility of fused and non-fused glands in biopsy specimens was analysed. Images of H&E stained slides of glands of carcinomas with Gleason score 6 and 7 (3+4) with and without glandular fusions with different lens magnification were analysed by 4 specialized genitourinary pathologists and 3 non-specialized pathologists. The definition of glandular fusion was a complete lack of any stromal fibres between a minimum of two glands and only one line of nuclei within the area of fusion. Overall agreement and interobserver reproducibility of fused versus non-fused glands of non- and uro-pathologically specialized pathologists were lower in lens magnification of 50× in contrast to 200×. The inter-observer reproducibility of fused glands by specialized observer was higher than that of nonspecialized pathologists. The results support the importance of strict but practicable criteria for the diagnosis of fused tumor glands in order to decrease the interobserver variability of Gleason scores, particularly in nonspecialised pathologists.
C1 [Helpap, Burkhard] Hegau-Bodensee Hospital of Singen, Department of Pathology, Virchow Str. 10, 78224 Singen, Germany.
[Kristiansen, Glen] University of Bonn, Institute of PathologyBonn, Germany.
[Beer, Michaela] University of Zurich, Institute of Surgical PathologyZurich, Switzerland.
[Kollermann, Jens] HSK- Hospital, Institute of PathologyWiesbaden, Germany.
[Oehler, Ulrich] Hegau-Bodensee Hospital of Singen, Department of Pathology, Virchow Str. 10, 78224 Singen, Germany.
[Pogrebniak, Alexsei] Hegau-Bodensee Hospital of Singen, Department of Pathology, Virchow Str. 10, 78224 Singen, Germany.
[Fellbaum, Christian] Hegau-Bodensee Hospital of Singen, Department of Pathology, Virchow Str. 10, 78224 Singen, Germany.
RP Helpap, B (reprint author), Hegau-Bodensee Hospital of Singen, Department of Pathology, 78224 Singen, Germany.
EM burkhard.helpap@hbh-kliniken.de
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Helpap B, Egevad L, 2008, Influence of the modified Gleason grading on pT stage and Gleason score of the prostate carcinoma after radical prostatectomy. Anal Quant Cytol Histol 30:1–7
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Helpap B, Kollermann J, 2012, Combined histoarchitectural and cytological biopsy grading improves grading accuracy in low grade prostate cancer. Int J Urol submitted
Egevad L, Algaba F, Berney D et al, 2011, Interactive digital slides with heat maps: a novel method to improve the reproducibility of Gleason grading. Virchows Arch 459:175–182
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 615
EP 621
DI 10.1007/s12253-011-9484-6
PG 7
ER
PT J
AU Jarai, T
Maasz, G
Burian, A
Bona, A
Jambor, E
Gerlinger, I
Mark, L
AF Jarai, Tamas
Maasz, Gabor
Burian, Andras
Bona, Agnes
Jambor, Eva
Gerlinger, Imre
Mark, Laszlo
TI Mass Spectrometry-Based Salivary Proteomics for the Discovery of Head and Neck Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarker discovery; MALDI TOF MS; Saliva; Tumor
ID Biomarker discovery; MALDI TOF MS; Saliva; Tumor
AB The 5-year survival rates for cases of head and neck squamous cell carcinoma (HNSCC) are only some 60%, mainly because 20%–40% of the patients develop a local relapse in the same or an adjacent anatomic region, even when the surgical margins are histologically tumour-free. Tumours are often discovered in an advanced stage because of the lack of specific symptoms and the diagnostic difficulties. The more advanced the stage of the tumour, the more invasive the diagnostic and treatment interventions needed. An early molecular diagnosis is therefore of vital importance in order to increase the survival rate. The aimof this study was to develop an efficient rapid and sensitive mass spectrometric method for the detection of differentially expressed proteins as tumourspecific biomarkers in saliva from HNSCC patients. Whole saliva samples were collected from patients with HNSCC and from healthy subjects. The proteins were profiled by using SDS PAGE, MALDI TOF/TOF mass spectrometry and the Mascot database search engine. Several potential tumour markers were identified, including annexin A1, beta- and gamma-actin, cytokeratin 4 and 13, zinc finger proteins and P53 pathway proteins. All of these proteins play a proven role in tumour genesis, and have not been detected previously in saliva. Salivary proteomics is a non-invasive specific method for cancer diagnosis and follow-up treatment. It provides facilities for the readily reproducible and reliable detection of tumours in early stages.
C1 [Jarai, Tamas] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti KlinikaPecs, Hungary.
[Maasz, Gabor] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti str. 12, 7624 Pecs, Hungary.
[Burian, Andras] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti KlinikaPecs, Hungary.
[Bona, Agnes] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti str. 12, 7624 Pecs, Hungary.
[Jambor, Eva] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti str. 12, 7624 Pecs, Hungary.
[Gerlinger, Imre] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti KlinikaPecs, Hungary.
[Mark, Laszlo] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti str. 12, 7624 Pecs, Hungary.
RP Mark, L (reprint author), University of Pecs, Institute of Biochemistry and Medical Chemistry, 7624 Pecs, Hungary.
EM laszlo.mark@aok.pte.hu
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Mahfouz ME, Rodrigo JP, Takes RP, Elsheikh MN, Rinaldo A, Brakenhoff RH, Ferlito A, 2010, Current potential and limitations of molecular diagnostic methods in head and neck cancer. Eur Arch Otorhinolaryngol 267:851–860
Mydlarz WK, Hennessey PT, Califano JA, 2010, Advances and perspectives in the molecular diagnosis of head and neck cancer. Expert Opin Med Diag 4:53–65
Xia SH, Hu LP, Hu H, Ying WT, Xu X, Cai Y, Han YL, Chen BS, Wei F, Qian XH, Cai YY, Shen Y, Wu M, Wang MR, 2002, Three isoforms of annexin I are preferentially expressed in normal esophageal epithelia but down-regulated in esophageal squamous cell carcinomas. Oncogene 21:6641–6648
Schaaij-Visser TB, Bremmer JF, Braakhuis BJ, Heck AJ, Slijper M, van der Waal I, Brakenhoff RH, 2010, Evaluation of cornulin, keratin 4, keratin 13 expression and grade of dysplasia for predicting malignant progression of oral leukoplakia. Oral Oncol 46:123– 127
Matsumoto I, Yamamoto M, 2005, Differential expression of the keratin-4, -13,-14, -17 and transglutaminase 3 genes during the development of oral squamous cell carcinoma from leukoplakia. Oral Oncol 41:607–613
Pedrero JMG, Fernandez MP, Morgan RO, Zapatero AH, Gonzalez MV, Nieto CS, Rodrigo JP, 2004, Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status. Am J Pathol 164:73–79
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Lin CY, Jeng YM, Chou HY, Hsu HC, Yuan RH, Chiang CP et al, 2008, Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma. J Surg Oncol 97:544–550
Lo WY, Tsai MH, Tsai Y, Hua CH, Tsai FJ, Huang SY, Tsai CH, Lai CC, 2007, Identification of overexpressed proteins in oral squamous cell carcinoma, OSCC, patients by clinical proteomic analysis. Clin Chim Acta 376:101–107
Makridakis M, Vlahou A, 2010, Secretome proteomics for discovery of cancer biomarkers. J Proteomics 73:2291–2305
Schaaij-Visser T, Brakenhoff RH, Leemans CR, Heck AJR, Slijper M, 2010, Protein biomarker discovery for head and neck cancer. J Proteomics 73:1790–1803
Schaaij-Visser TB, Graveland AP, Gauci S, Braakhuis BJ, Buijze M, Heck AJ et al, 2009, Differential proteomics identifies protein biomarkers that predict local relapse of head and neck squamous cell carcinomas. Clin Cancer Res 15:7666–7675
Wadsworth JD, Somers K, Stack BC, Cazare L, Malik G, Adam BL, Wright GL, Semmes JO, 2004, Identification of patients with head and neck cancer using serum protein profiles. Arch Otolaryngol Head Neck Surg 130:98–104
Wu W, Tang X, Hu W, Lotan R, Hong WK, Mao L, 2002, Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry. Clin Exp Metastasis 19:319–326
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 623
EP 628
DI 10.1007/s12253-011-9486-4
PG 6
ER
PT J
AU Cui, Q
Li, D
Zhang, J
Wang, X
Liu, Sh
Wang, L
Zhang, P
Zhou, J
Liu, Ch
Jiang, W
Zeng, Y
AF Cui, Qiu
Li, Dingfeng
Zhang, Jing
Wang, Xiaohong
Liu, Shubin
Wang, Lei
Zhang, Ping
Zhou, Ju
Liu, Cheng
Jiang, Weihao
Zeng, Yanjun
TI The Significance of Preoperative Chemotherapy in Evaluation of Recurrent Soft Tissue Liposarcoma Necrosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Implantable intra-arterial induction chemotherapy; Liposarcoma; Cisplatin; Doxorubicin; Caffeine
ID Implantable intra-arterial induction chemotherapy; Liposarcoma; Cisplatin; Doxorubicin; Caffeine
AB To investigate the effect of preoperative induction chemotherapy on treatment of recurrent liposarcoma. 21 patients with recurrent liposarcoma received the treatment of preoperative intra-arterial chemotherapy and surgical resection. Intra-arterial chemotherapy was given by subcutaneous implantable drug delivery system with infusion of cisplatin and doxorubicin followed by caffeine. After treatment, patients were followed up for 39 months. The liposarcoma changes in CT imaging were observed in 18 cases and there were 15 cases with medium or severe pathological changes caused by chemotherapy. At the end of the postoperative follow-up of 39 months, liposarcoma reoccurred locally in 2 cases; pulmonary metastasis occurred in 1 case and death in 3 cases. Preoperative intra-arterial chemotherapy is effective for highly malignant tumors such as recurrent liposarcoma and the judgment of prognosis is based on the postoperative pathological changes of such tumor.
C1 [Cui, Qiu] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Li, Dingfeng] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Zhang, Jing] Beijing University of Technology, Biomedical Engineering Center, 100022 Beijing, China.
[Wang, Xiaohong] Beijing University of Technology, Biomedical Engineering Center, 100022 Beijing, China.
[Liu, Shubin] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Wang, Lei] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Zhang, Ping] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Zhou, Ju] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Liu, Cheng] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Jiang, Weihao] 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
[Zeng, Yanjun] Beijing University of Technology, Biomedical Engineering Center, 100022 Beijing, China.
RP Li, D (reprint author), 307th Hospital of PLA, Department of Bone Tumor, 100071 Beijing, China.
EM 307yygk@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 629
EP 633
DI 10.1007/s12253-011-9487-3
PG 5
ER
PT J
AU Guo, X
Xiong, L
Zou, L
Zhao, J
AF Guo, Xiaodong
Xiong, Lu
Zou, Lin
Zhao, Jingmin
TI Upregulation of Bone Morphogenetic Protein 4 is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Bone morphogenetic protein 4; Prognosis
ID Hepatocellular carcinoma; Bone morphogenetic protein 4; Prognosis
AB Bone morphogenetic protein (BMP) 4 plays a crucial role in tumor invasion and metastasis of various human cancers. However, little is known about the correlation of BMP4 expression with clinical aggressiveness and prognosis in hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of BMP4 in HCC and determine its correlation with tumor progression and prognosis. Immunohistochemistry assay was used to determine the expression of BMP4 in HCC and corresponding paracarcinomatous tissues from 156 patients. The potential prognostic value of BMP4 was investigated by comparing the survival rates between the BMP4-positive and BMP4-negative HCC patients. Immunohistochemically, BMP4 protein expression in the HCC tissues (120/156, 76.9%) was significantly higher than that in the paracarcinomatous tissues (19/156, 12.2%, P<0.01). The expression of BMP4 in HCC was associated with number of tumor nodules (P00.02), Edmondson grade (P00.03), TNM stage (P00.009), and vascular invasion (>P00.006). In univariate survival analysis, the significant associations of the BMP4 protein overexpression with shortened patients’ overall and disease-free survival were found (P00.001 and 0.006, respectively). Furthermore, its expression was found to be an independent factor for predicting both overall (P00.009) and disease-free survival (P00.022) of HCC in multivariate analysis. Our data suggest for the first time that BMP4 is overexpressed in HCC tissues and may also act as a novel marker for predicting the recurrence and prognosis of HCC patients after surgery.
C1 [Guo, Xiaodong] Chinese PLA Postgraduate Medical School, 100853 Beijing, China.
[Xiong, Lu] 302 Hospital of PLA, 100039 Beijing, China.
[Zou, Lin] Chinese PLA General Hospital, 100853 Beijing, China.
[Zhao, Jingmin] 302 Hospital of PLA, 100039 Beijing, China.
RP Zhao, J (reprint author), 302 Hospital of PLA, 100039 Beijing, China.
EM zhaojingmin302@163.com
CR Yang H, Lin M, Xiong F, Yang Y, Nie X, McNutt MA, Zhou R, 2011, Combined lysosomal protein transmembrane 4 beta-35 and argininosuccinate synthetase expression predicts clinical outcome in hepatocellular carcinoma patients. Surg Today 41:810–817
Farazi PA, DePinho RA, 2006, Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6:674–687
Thorgeirsson SS, Grisham JW, 2002, Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31:339–346
Chen D, Zhao M, Mundy GR, 2004, Bone morphogenetic proteins. Growth Factors 22:233–241
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Marki D, Celi T, Grkovi A, Spanjol J, Fukar Z, Grahovac B, Ethorevi G, Bobinac D, 2011, mRNA expression of bone morphogenetic proteins and their receptors in human renal cell carcinoma. Urol Int In press
Yuen HF, Chan YP, Cheung WL, Wong YC, Wang X, Chan KW, 2008, The prognostic significance of BMP-6 signaling in prostate cancer. Mod Pathol 21:1436–1443
Motoyama K, Tanaka F, Kosaka Y, Mimori K, Uetake H, Inoue H, Sugihara K, Mori M, 2008, Clinical significance of BMP7 in human colorectal cancer. Ann Surg Oncol 15:1530–1537
Hogan BL, 1996, Bone morphogenetic proteins in development. Curr Opin Genet Dev 6:432–438
Virtanen S, Alarmo EL, Sandstrom S, Ampuja M, Kallioniemi A, 2011, Bone morphogenetic protein −4 and −5 in pancreatic cancer– novel bidirectional players. Exp Cell Res 317:2136–2146
McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, Cabrera L, Keller E, McCauley L, Cho KR, Buckanovich RJ, 2011, Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest 121:3206–3219
Slattery ML, Lundgreen A, Herrick JS, Kadlubar S, Caan BJ, Potter JD, Wolff RK, 2011, Genetic variation in bone morphogenetic protein and colon and rectal cancer. Int J Cancer In press
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Slattery ML, Lundgreen A, Herrick JS, Wolff RK, Caan BJ, 2011, Genetic variation in the transforming growth factor-β signaling pathway and survival after diagnosis with colon and rectal cancer. Cancer 117:4175–4183
Lombardo Y, Scopelliti A, Cammareri P, Todaro M, Iovino F, Ricci-Vitiani L, Gulotta G, Dieli F, de Maria R, Stassi G, 2011, Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice. Gastroenterology 140:297–309
LeeYC, ChengCJ, BilenMA, Lu JF, Satcher RL,Yu-Lee LY,Gallick GE,Maity SN, Lin SH(2011, BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res 71:5194–5203
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Hamada S, Satoh K, Hirota M, Fujibuchi W, Kanno A, Umino J, Ito H, Satoh A, Kikuta K, Kume K, Masamune A, Shimosegawa T, 2009, Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines. Cancer Sci 100:103–110
Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, Brem H, Olivi A, Dimeco F, Vescovi AL, 2006, Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–765
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 635
EP 640
DI 10.1007/s12253-011-9488-2
PG 6
ER
PT J
AU Katz, S
Balogh, P
Nagy, N
Kiss, LA
AF Katz, Sandor
Balogh, Petra
Nagy, Nandor
Kiss, L Anna
TI Epithelial-To-Mesenchymal Transition Induced by Freund’s Adjuvant Treatment in Rat Mesothelial Cells: A Morphological and Immunocytochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveolin-1/caveolae; Epithelial-tomesenchymal transition; Mesothelial cell; Transdifferentiation
ID Caveolin-1/caveolae; Epithelial-tomesenchymal transition; Mesothelial cell; Transdifferentiation
AB Intraperitoneal injection of Freund’s adjuvant induces acute peritonitis. By the time of the Freund’s adjuvant treatment the flat, simple squamous epithelial cells became rounded, cuboidal shaped, many of them have lost their connection with the neighbouring cells and detached from the basement membrane. The macrophage markers’ (ED1, OX43 and CD68) expression also increased in the mesothelial cells and more mesothelin and anti-ED1 doublelabelled cells were found freely present close to the surface. The cytokeratin expression of the mesothelial cells has gradually decreased. At the 5th day of the inflammation practically there was no cytokeratin labelling present in the mesothelial cells and the mesothelin expression has significantly decreased. Parallel to this mesothelial cells started to express vimentin, a characteristic mesenchymal intermediate filament protein indicating that they gradually lost their epithelial character and gained mesenchymal phenotype. These results strongly suggest that under the effect of Freund’s adjuvant treatment (inflammation) mesothelial cells can undergo epithelial-to-mesenchymal transition and differentiate into phagocytotic (macrophage-like) cells. Studying the caveolae/caveolin-1 on the plasma membrane of mesothelial cells we found that the Freund’s adjuvant treatment has changed the cellular distribution of caveolin-1: as the inflammation progressed strong caveolin-1 labelling was found inside of the cytoplasm(in perinuclear localization) indicating that inflammation induced the caveolae internalization. These results indicate that caveolae/caveolin-1 might play important regulatory role in signal transduction leading to trasdifferentiation.
C1 [Katz, Sandor] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58Budapest, Hungary.
[Balogh, Petra] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58Budapest, Hungary.
[Nagy, Nandor] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58Budapest, Hungary.
[Kiss, L Anna] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58Budapest, Hungary.
RP Katz, S (reprint author), Semmelweis University, 1st Department of Anatomy, Budapest, Hungary.
EM katzsanya@gmail.com
CR Savagner P, 2001, Leaving the neighbourhood: Molecular mechanisms involved during epithelial-mesenchymal transition. Bioesssay 23:912–923
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Moustakas A, Pardali K, Gaal A, Heldin CH, 2002, Mechanisms of TGF-beta signalling in regulation of cell growth and differentiation. Immunol Lett 82:85–91
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Boyer B, Valles AM, Edme N, 2000, Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol 60:1091– 1099
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Yanez-Mo M, Lara-Pezzi E, Selgas R, Ramirez-Huesca M et al, 2003, Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. New England J Medicine 348:403–413
von Ruhland CJ, Campbell L, Gumbleton M, Jasani B, Newman G, 2004, Immunolocalization of caveolin-1 in rat and human mesothelium. JHistochem and Cytochem 52:1415–1425
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Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL, Arteaga CL, 2000, Phosphatidyl inositol 3-kinase function is required for TGFbeta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 275:36803–36810
Patel HH, Murray F, Insel PA, 2008, Caveolae as organizers of pharmacologically relevant signa transduction molecules. Ann Rev Pharmacol Toxicol 48:359–391
Pelkmans L, Helenius A, 2002, Endocytosis via caveolae. Traffic 3:311–320
Krajewska WM, Maslowska I, 2004, Caveolins: structure and function in signal transduction. Cell Mol Biol Lett 9:195–220
Razani B, Zhang ZL, Bitzer M, von Gersdorff G, Bottinger EP, Lisanti MP, 2001, Caveolin-1 regulates transforming growth factor, TGF)-ß-SMAD signalling through an interaction with the TGF-ß type I receptor. J Biol Chem 276:6727–6738
Zwaagstra JC, El-Alfy M, O’Connor-McCourt MD, 2001, Transforming growth factor, TGF)-ß 1 internalization: modulation by ligand interaction with TGF-ß receptors types I and II and a mechanism that is distinct from clathrin-mediated endocytosis. J Biol Chem 276:27237–27245
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 641
EP 649
DI 10.1007/s12253-011-9489-1
PG 9
ER
PT J
AU Ebrahimkhani, S
Asgharian, MA
Nourinaier, B
Ebrahimkhani, K
Vali, N
Abbasi, F
Zali, RM
AF Ebrahimkhani, Saeideh
Asgharian, Mohammad Ali
Nourinaier, Babak
Ebrahimkhani, Khadijeh
Vali, Nasrin
Abbasi, Fatemeh
Zali, Reza Mohammad
TI Association of GSTM1, GSTT1, GSTP1 and CYP2E1 Single Nucleotide Polymorphisms with Colorectal Cancer in Iran
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glutathione S-transferases; Colorectal cancer; Cytochrome P4502E1; Iran
ID Glutathione S-transferases; Colorectal cancer; Cytochrome P4502E1; Iran
AB Colorectal cancer is a major cause of morbidity and mortality both globally and in Iran. The aim of this study was to determine the association between genetic polymorphisms of glutathione S-transferases P1, M1 and T1 (GSTP1, M1, T1) and susceptibility to colorectal cancer (CRC). Genotyping of GSTP1, GSTM1 and GSTT1 was performed by the use of pyrosequencing. One hundred cases and healthy controls were enrolled into this study. Mean GSTT1 polymorphism type was significantly (P<0.01) higher in cases as compared to controls (P<0.0001: OR, 2.43: 95% CI, 1.47-4). On the other hand there is no significant association between GSTM1, GSTP1 and colorectal cancer. GSTs measurement may be useful as a colorectal marker in colorectal cancer and biopsies obtained at colonoscopy can be used to measure tumor markers.
C1 [Ebrahimkhani, Saeideh] Shahid Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Taleghani st- EvinTehran, Iran.
[Asgharian, Mohammad Ali] Islamic Azad University, Department of Cell and Molecular Biology, Tonekabon BranchTonekabon, Iran.
[Nourinaier, Babak] Shahid Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Taleghani st- EvinTehran, Iran.
[Ebrahimkhani, Khadijeh] Zanjan University of Medical ScienceZanjan, Iran.
[Vali, Nasrin] Shahid Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Taleghani st- EvinTehran, Iran.
[Abbasi, Fatemeh] Azarbaijan Tarbiat Molaem University, Department of Cell and Molecular BiologyTonekabon, Iran.
[Zali, Reza Mohammad] Shahid Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Taleghani st- EvinTehran, Iran.
RP Zali, RM (reprint author), Shahid Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Tehran, Iran.
EM mrzali55@yahoo.com
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Nakajima T, Wang R-S, Nimura Y et al, 1996, Expression of cytochrome P450s and glutathione S- transferases in human esophagus with squamous- cell carcinomas. Carcinogenesis 17:1477–1481
Boyer TD, Kenney WC, 1985, Preparation, characterization and properties of glutathione S-transferases. In: Zakim D, Vessey D, eds, Biochemical pharmacology and toxicology.Wiley, New York
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Meyer DJ, Coles B, Pemble SE, Gilmore KS, Fraser GM, Ketterer B, 1991, θ, a new class of glutathione transferases purified from rat and man. Biochem J 274:409–414
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF, 1994, Effects of human and rat glutathione S-transferases on the covalent bonding of the N-acetoxy derivatives of heterocyclic amine carcinogens in vitro: a possible mechanism of organ specificity in their carcinogenesis. Cancer Res 54:4920–4926
Pemble S, Schroeder KR, Spenser SR et al, 1994, Human glutathione S-transferase, GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276
EvansWE, RellingMV(1999, Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487–91
Rebbeck TR, 1997, Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomark Prev 6:733–743
Strange RC, Lear JT, Fryer AA, 1998, Glutathione S-transferase polymorphisms: influence on susceptibility to cancer. Chem Biol Interact 24(111–112):351–364
Nomania H, Mohammadzadeh Ghobadloob S, Yaghmaeib B, Rezvaniea NA, Yaghmaeic K, 2005, Glutathione S-transferases activity in patients with colorectal cancer. Clin Biochem 38:621–624
Rajagopal R, Deakin M, Fawole AS et al, 2005, Glutathione Stransferase T1 polymorphisms are associated with outcome in colorectal cancer. Carcinogenesis 26(12):2157–2163
Srivastava SK, Singhal SS, Hu X, Awasthi YC, Zimniak P, Singh SV, 1999, Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Biophys 366:89–94
Houlston RS, 1999, Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 8:675–682
Baily R, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl F, 1998, Breast cancer and CYP1A1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70
Saadat I, Saadat M, 2001, Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Letters 169:21–26
de Jong M, Nolte IM, te Meerman GJ et al, 2002, Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev 11:1332–52
Board PG, 1981, Gene deletion and partial deficiency of the glutathione S-transferase, ligandin, system in man. FEBS Lett 135:12–14
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Xing D, Tan W, Song N, Lin D, 2000, Genetic polymorphism in hOGG1and susceptibility to esophageal cancer in Chinese. Zhonghuayixue Yichuanxue Zazhi 17:377–380
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Tan W, Song N, Wang GQ et al, 2000, Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev 9:551–556
Dong CH, Yu SZ, Chen GC, Zhao DM, Hu Y, 1998, Association of polymorphisms of glutathioneS transferase M1 and T1 genotypes with elevated aflatoxin and increased risk of primary liver cancer. Shijie Huaren Xiaohua Zazhi 6:463–466
Thong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK, 1993, Relationship between the GSTMI genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824
Chevenix-Trench G, Young J, Coggan M, Board P, 1995, Glutathione S-transferase Ml, and Tl polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis 16:1655–1657
Katoh T, Nagata N, Kuroda Y et al, 1996, Glutathione Stransferase MI, GSTM1), and Tl(GSTT1, genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis 17:1855–1859
Deakin M, Elder J, Hendrickse C et al, 1996, Glutathione Stransferase GSTI’l genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 17:881–884
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 651
EP 656
DI 10.1007/s12253-011-9490-8
PG 6
ER
PT J
AU Li, Z
Liao, Q
Wu, Y
Liao, M
Hao, Y
Zhang, Sh
Song, Sh
Li, B
Zhang, Yd
AF Li, Zhehai
Liao, Qiande
Wu, Yuchi
Liao, Mingmei
Hao, Yuqin
Zhang, Shengbin
Song, Shipeng
Li, Bing
Zhang, Yang-de
TI Upregulation of a Disintegrin and Metalloprotease 8 Influences Tumor Metastasis and Prognosis in Patients with Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; A disintegrin and metalloprotease 8; Immunohistochemistry; Prognosis; Overall survival; Disease-free survival
ID Osteosarcoma; A disintegrin and metalloprotease 8; Immunohistochemistry; Prognosis; Overall survival; Disease-free survival
AB To investigate the clinicopathological and prognostic value of a disintegrin and metalloprotease 8 (ADAM8) in osteosarcoma. ADAM8 expression in osteosarcoma tissues was examined by immunohistochemistry in 69 patients. ADAM8 was positively expressed in 61 of 69 (88.4%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (P00.008) and metastasis (P00.002). Patients with strong ADAM8 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P<0.001) when compared with the patients with the weak expression of ADAM8. On multivariate analysis, ADAM8 expression was found to be an independent prognostic factor for both OS (P<0.001) and DFS (P<0.001). Our results suggest for the first time that ADAM8 might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with osteosarcoma.
C1 [Li, Zhehai] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87, 410078 Changsha, Hunan, China.
[Liao, Qiande] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87, 410078 Changsha, Hunan, China.
[Wu, Yuchi] Inner Mongolia Medical College, The Third Affiliated Hospital, Shaoxian Road 20, Kun District, 014010 Baotou, Inner Mongolia, China.
[Liao, Mingmei] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87, 410078 Changsha, Hunan, China.
[Hao, Yuqin] Inner Mongolia Medical College, The Third Affiliated Hospital, Shaoxian Road 20, Kun District, 014010 Baotou, Inner Mongolia, China.
[Zhang, Shengbin] Inner Mongolia Medical College, The Third Affiliated Hospital, Shaoxian Road 20, Kun District, 014010 Baotou, Inner Mongolia, China.
[Song, Shipeng] Inner Mongolia Medical College, The Third Affiliated Hospital, Shaoxian Road 20, Kun District, 014010 Baotou, Inner Mongolia, China.
[Li, Bing] Inner Mongolia Medical College, The Third Affiliated Hospital, Shaoxian Road 20, Kun District, 014010 Baotou, Inner Mongolia, China.
[Zhang, Yang-de] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87, 410078 Changsha, Hunan, China.
RP Zhang, Yd (reprint author), Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410078 Changsha, China.
EM zydjs@sohu.com
CR Urakawa H, Nishida Y, Naruse T, Nakashima H, Ishiguro N, 2009, Cyclooxygenase-2 overexpression predicts poor survival in patients with high-grade extremity osteosarcoma: a pilot study. Clin Orthop Relat Res 467:2932–2938
Yao Y, Dong Y, Lin F et al, 2009, The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep 21:229–235
Jaffe N, 2009, Adjuvant chemotherapy in osteosarcoma: an odyssey of rejection and vindication. In: Jaffe N, Bielack SS, Bruland OS, eds, Pediatric and adolescent osteosarcoma, cancer treatment and research. Springer, New York, p 152
Wang YC, Zheng LH, Ma BA et al, 2011, Clinical value of signal transducers and activators of transcription 3, STAT3, gene expression in human osteosarcoma. Acta Histochem 113:402–408
Dijkstra A, Postma DS, Noordhoek JA et al, 2009, Expression of ADAMs, “a disintegrin and metalloprotease”, in the human lung. Virchows Arch 454:441–449
Mochizuki S, Okada Y, 2007, ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628
Hernandez I, Moreno JL, Zandueta C, Montuenga L, Lecanda F, 2010, Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer. Oncogene 29:3758–3769
Hall T, Pegg LE, Pauley AM, Fischer HD, Tomasselli AG, Zack MD, 2009, ADAM8 substrate specificity: influence of pH on preprocessing and proteoglycan degradation. Arch Biochem Biophys 491:106–111
Zack MD, Melton MA, Stock JL et al, 2009, Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8, ADAM8). Clin Exp Immunol 158:246–256
Ishizuka H, Garcia-Palacios V, Lu G et al, 2011, ADAM8 enhances osteoclast precursor fusion and osteoclast formation in vitro and in vivo. J Bone Miner Res 26:169–181
Ishikawa N, Daigo Y, Yasui W, 2004, ADAM8 as a novel serological and histochemical marker for lung cancer. Clin Cancer Res 10:8363–8370
Roemer A, Schwettmann L, Jung M, 2004, The membrane proteases adams and hepsin are differentially expressed in renal cell carcinoma. Are they potential tumor markers? J Urol 172:2162– 2166
Fritzsche FR, Jung M, Xu C, 2006, ADAM8 expression in prostate cancer is associated with parameters of unfavorable prognosis. Virchows Arch 449:628–636
Ainola M, Li TF, Mandelin J et al, 2009, Involvement of a disintegrin and a metalloproteinase 8, ADAM8, in osteoclastogenesis and pathological bone destruction. Ann Rheum Dis 68:427–434
Choi SJ, Han JH, Roodman GD, 2001, ADAM8: a novel osteoclast stimulating factor. J Bone Miner Res 16:814–822
Mandelin J, Li TF, Hukkanen MV, 2003, Increased expression of a novel osteoclast-stimulating factor, ADAM8, in interface tissue around loosened hip prostheses. J Rheumatol 30:2033–2038
Egeblad M, Werb Z, 2002, New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174
Shiomi T, Okada Y, 2003, MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev 22:145–152
Wildeboer D, Naus S, Amy Sang QX, Bartsch JW, Pagenstecher A, 2006, Metalloproteinase disintegrins ADAM8 and ADAM19 are highly regulated in human primary brain tumors and their expression levels and activities are associated with invasiveness. J Neuropathol Exp Neurol 65:516–527
Valkovskaya N, Kayed H, Felix K et al, 2007, ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer. J Cell Mol Med 11:1162–1174
Valkovskaya NV, 2008, Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines. Exp Oncol 30:129– 132
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 657
EP 661
DI 10.1007/s12253-011-9491-7
PG 5
ER
PT J
AU Carmignani, L
Picozzi, S
Casellato, S
Bozzini, G
Marenghi, C
Macchi, A
Lunelli, L
Rubino, B
Clemente, C
AF Carmignani, Luca
Picozzi, Stefano
Casellato, Stefano
Bozzini, Giorgio
Marenghi, Carlo
Macchi, Alberto
Lunelli, Luca
Rubino, Barbara
Clemente, Claudio
TI A Proposed New Technique in Prostate Cancer Tissue Bio-Banking: Our Experience with a New Protocol
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate; Cancer; Prostate cancer; Bio-bank; Tissue; Biopsy
ID Prostate; Cancer; Prostate cancer; Bio-bank; Tissue; Biopsy
AB The aim of our study, beyond validating a method of collecting and storing biological samples from patients with prostate cancer, was to validate an innovative biopsy method for the creation of a biobank of prostatic frozen tissues. Patients referred to our hospital between November 2008 and March 2010 to undergo radical prostatectomy were invited to participate in the study. Each patient’s data were stored in two databases (personal information and clinical database) while samples of urine, blood and its derivatives, fresh material and formalin-processed tissue were stored in a correlated biobank. The proposed method for collecting fresh material was to take samples of the neoplastic tissue by carrying out targeted biopsies in the area indicated by the biopsy mapping as the site of the malignancy, under manual palpation to identify the neoplastic nodule. The site of sampling was marked by an injection of India ink. 55 patients agreed to participate in the study. In 43 cases biopsies were correct, with a mean of 48% of core involved by tumour (range, 10–90%). Overall the tumour detection rate was 78.2%. The protocol for collecting biological material and the new method for collecting fresh tissue reduce internal steps and staff involved, thereby reducing all those variables that cause heterogeneity of material and changes in its quality. This process provides high quality, low cost material for research on prostate cancer. The features of the collection protocol mean that the protocol can also be used in non-academic centres with only limited research funds.
C1 [Carmignani, Luca] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Picozzi, Stefano] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Casellato, Stefano] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Bozzini, Giorgio] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Marenghi, Carlo] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Macchi, Alberto] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Lunelli, Luca] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Rubino, Barbara] Istituto Clinico S. Ambrogio, Division of Pathology, Via Faravelli 16, 20149 Milan, Italy.
[Clemente, Claudio] Istituto Clinico S. Ambrogio, Division of Pathology, Via Faravelli 16, 20149 Milan, Italy.
RP Picozzi, S (reprint author), IRCCS Policlinico San Donato, University of Milan, Urology Department, 20097 San Donato Milanese, Italy.
EM stepico@tin.it
CR Dhir R, 2008, Prostate cancer biobanking. Curr Opin Urol 18:309–14
Melamed J, Datta MW, Becich MJ et al, 2004, The cooperative prostate cancer tissue resource: a specimen and data resource for cancer researchers. Clin Cancer Res 10:4614–21
Bova GS, Fox WM, Epstein JI, 1993, Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. Mod Pathol 6:201–7
Bonavina L, Laface L, Picozzi S et al, 2010, Proposal of a punch biopsy protocol as a pre-requisite for the establishment of a tissue bank from resected esophageal tumors. Pathol Oncol Res 16:457–60
Greene FL, Page DL, Fleming ID et al, 2002, AJCC Cancer Staging Manual, 6th edn. Springer, New York, NY
Bosso N, Chinello C, Picozzi SC et al, 2008, Human urine biomarkers of renal cell carcinoma evaluated by ClinProt. Proteomics Clin Appl 2:1036–46
Hulmes JD, Bethea D, Ho K et al, 2004, An investigation of plasma collection, stabilization, and storage procedures for proteomic analysis of clinical samples. Clinical Proteomics 1:17–31
Thongboonkerd V, 2007, Proteomics of human body fluids: principles, methods, and applications. Humana Press Inc., New Jersey
Gore JL, Shariat SF, Miles BJ et al, 2001, Optimal combinations of systematic sextant and laterally directed biopsies for the detection of prostate cancer. J Urol 165:1554–9
Etzioni R, Penson DF, Legler JM et al, 2002, Overdiagnosis due to prostate-specific antigen screening: Lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 94:981–990
Johansson JE, Andren O, Andersson SO et al, 2004, Natural history of early, localized prostate cancer. JAMA 291:2713–9
Schroeder FH, Hugosson J, Roobol MJ et al, 2009, Screening and prostate-cancer mortality in a randomized European study. N Eng J Med 360:1320–8
http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-99–012.html.
Milanes-Yearsley M, Hammond ME, Pajak TF et al, 2002, Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups. Mod Pathol 15:1366–73
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 663
EP 668
DI 10.1007/s12253-011-9492-6
PG 6
ER
PT J
AU Nagy, Zs
Horvath, O
Kadas, J
Valtinyi, D
Laszlo, L
Kopper, B
Blasko, Gy
AF Nagy, Zsuzsanna
Horvath, Orsolya
Kadas, Julia
Valtinyi, Dorottya
Laszlo, Larisza
Kopper, Bence
Blasko, Gyorgy
TI D-Dimer as a Potential Prognostic Marker
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; LMWH; D-dimer; prognostic marker; solid tumors
ID cancer; LMWH; D-dimer; prognostic marker; solid tumors
AB Malignant tumors are often accompanied by increased risk for procoagulant activity, thrombosis and embolism. As a marker indicating such disturbancies is D-dimer, a product of fibrinolysis. In this retrospective study almost 300 patients with malignant tumors were evaluated. During LMWH treatment (as thromboprophylaxis) the highest frequency of VTE with worst prognosis occurred in pancreatic cancer (partly due to the late discovery) followed by ovarian, colonic and breast cancers. Also, increased D-dimer level correlated with progression (stages) and high mortality rate. Furthermore, D-dimer showed very similar or better prognostic activity than the clinically widely used classic tumor markers and suggested to use it as an additional value.
C1 [Nagy, Zsuzsanna] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Horvath, Orsolya] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Kadas, Julia] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Valtinyi, Dorottya] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Laszlo, Larisza] St. Imre Hospital, Department Clinical Oncology, Tetenyi ut 12-15, 1116 Budapest, Hungary.
[Kopper, Bence] Semmelweis University, Department of Biophysics and Radiation BiologyBudapest, Hungary.
[Blasko, Gyorgy] University of Debrecen, Department of Pharmacology and PharmacotherapyDebrecen, Hungary.
RP Nagy, Zs (reprint author), St. Imre Hospital, Department Clinical Oncology, 1116 Budapest, Hungary.
EM zsulacz@chello.hu
CR Bouillard JB, Bouillaud S, 1823, De l’Obliteration des veines et de son influence sur la formation des hydropisies partielles: consideration sur la hydropisies passive et general. Arch GenMed 1:188–204
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Blom JW, Doggen CJ, Osanto S, Rosendaal FR, 2005, malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293:492–496
Murchinson JT, Wylie L, Stockton DL, 2004, Excess risk of cancer in patients with primary venous thromboembolism: a national, population-based cohort study. Br J Cancer 91:92–95
Noble S, Pasi J, 2010, Epidemiology and pathophysiology of cancer-associated thrombosis. Brit J Cancer 102:52–59
Kakkar AK, 2005, Low molecular weight heparin and survival in patients with malignant disease. Cancer Control 12:22–30
Kakkar AK, Levine MN, Kadziola Z, 2004, Low molecular weight heparin, therapy with deltaparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study, FAMOUS). J Clin Oncol 22:1944–1948
Klerk CPW, Smorenburg SM, Otten H-M et al, 2005, The effect of low molecular weight heparin on survivcal in patients with advanced malignancy. J Clin Oncol 23:2130–2135
Tovari J, Berecky B, Gilly R et al, 2004, Effect of heparin treatment on the metastatization of melanoma in a preclinical model, in Hungarian). Magyar Onkologia 48:235–241
Lazo-Langer A, Gross GD, Spaans JN et al, 2007, The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trial. Thromb Hemostasis 5:729–737
Niers TMH, Bruggeman LW, Van Sluis GL et al, 2009, Long-term thrombin inhibition promotes cancer cell extravasation in a mouse model of experimental metastasis. Internat Soc Thrombosis Haemostasis 7:1595–1597
Mousa SA, Petersen LJ, 2009, Anticancer properties of lowmolecular- weight heparin: preclinical evidence. Thromb Haemost 102:258–267
Borsig I, 2010, Antimetastatic effect of heparins and modified heparins. Experimental evidence. Thrombosis Res 125(suppl 2): S66–S71
Kenessey I, Simon E, Futosi K et al, 2009, Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical humanmelanoma metastasis model. Thromb Haemost 102:1265–1273
Nadir Y, Brenner B, 2010, Heparanase procoagulant effects and inhibition by heparins. Thromb Res 125(suppl 2):572–576
Kvolik S, Jukic M, Matijevic M et al, 2010, An overview of coagulation disorders in cancer patients. Surg Oncol 29:e33–e46
Khorana AA, Kunderer NM, Culakova E et al, 2008, Development and validation of a predictive model for chemotherapyassociated thrombosis. Blood 111:4902–4907
Doormaal FF et al, 2011, Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol 29:2701–2706
Zs N, Turcsik V, Gy B, 2009, The effect of LMWH, Nadroparin, on Tumor progression. Pathol Oncol Res Path Oncol Res 15:689– 692
Kulasingam V, Pavlou MR, Diamandis EP, 2010, Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer. Nature Cancer Rev 10:371–378
Moore RG et al, 2009, A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 112:40–46
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 669
EP 674
DI 10.1007/s12253-011-9493-5
PG 6
ER
PT J
AU Andjelic, MB
Mihaljevic, SB
Jakovic, RL
AF Andjelic, M Bosko
Mihaljevic, S Biljana
Jakovic, R Ljubomir
TI ABVD as the Treatment Option in Advanced Hodgkin’s Lymphoma Patients Older than 45 Years
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Advanced Hodgkin’s lymphoma; Elderly patients
ID Advanced Hodgkin’s lymphoma; Elderly patients
AB Advanced age is considered an unfavourable prognostic factor for Hodgkin’s lymphoma (HL). The optimal treatment for these patients is not yet defined, especially for the advanced stages. We analysed the outcome and prognostic relevance of patient and disease characteristics in 46 advanced stage HL patients who were older than 45 years, treated with ABVD. Elderly patients (>60 year) had a significantly higher rate of comorbidities (p<0.05). The complete remission rate was significantly lower in elderly patients and in patients with an IPS ≥3 (p<0.05, p<0.05, respectively). Elderly patients had significantly shorter event-free survival (p<0.01) and overall survival (p<0.01) compared to patients of 45–60 year. Extranodal disease, an IPS ≥3, bulky disease, an ESR>50 and the presence of a large mediastinal tumour mass didn’t have an influence on survival (p>0.05). The multivariate Cox regression analysis identified the age of >60 year as an independent prognostic factor. The prospective clinical trials seem to be needed for defining the optimal therapeutic approach in elderly patients.
C1 [Andjelic, M Bosko] Clinical Center of Serbia, Clinic for Hematology, 2 Koste Todorovic St, 11000 Belgrade, Serbia.
[Mihaljevic, S Biljana] Clinical Center of Serbia, Clinic for Hematology, 2 Koste Todorovic St, 11000 Belgrade, Serbia.
[Jakovic, R Ljubomir] Clinical Center of Serbia, Clinic for Hematology, 2 Koste Todorovic St, 11000 Belgrade, Serbia.
RP Andjelic, MB (reprint author), Clinical Center of Serbia, Clinic for Hematology, 11000 Belgrade, Serbia.
EM boleoli@sezampro.rs
CR Brusamolino E, Bacigalupo A, Barosi G et al, 2009, Classical Hodgkin’s lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up. Haematologica 94:550–565
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 675
EP 680
DI 10.1007/s12253-011-9494-4
PG 6
ER
PT J
AU Savic, A
Cemerikic-Martinovic, V
Dovat, S
Rajic, N
Urosevic, I
Sekulic, B
Kvrgic, V
Popovic, S
AF Savic, Aleksandar
Cemerikic-Martinovic, Vesna
Dovat, Sinisa
Rajic, Nebojsa
Urosevic, Ivana
Sekulic, Borivoj
Kvrgic, Vanja
Popovic, Stevan
TI Angiogenesis and Survival in Patients with Myelodysplastic Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myelodysplastic syndrome; Angiogenesis; Microvessel density; VEGF; Survival; Prognosis
ID Myelodysplastic syndrome; Angiogenesis; Microvessel density; VEGF; Survival; Prognosis
AB Angiogenesis has been implicated in the pathogenesis and prognosis of myelodysplastic syndrome (MDS). In this study, we investigated the relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, common morphological and clinical factors, and survival in patients with MDS. We examined the MVD of paraffin-embedded bone marrow sections from 70 MDS patients and 31 controls. VEGF expression was determined in 50 patients and 20 controls. The median MVD in MDS patients was significantly higher than that in controls (p00.025), whereas there was no difference in VEGF expression between MDS patients and controls. In univariate analysis, increased MVD was associated with a shorter survival time (p00.023). However, in multivariate analysis, MVD was not an independent predictor of survival. The VEGF expression did not influence survival in univariate analysis. Survival was independently influenced by platelet count (p00.0073), cytogenetic risk category (p00.022), and transfusion dependence (p00.0073). Neither MVD nor VEGF expression were predictors for progression to acute myeloid leukemia in univariate analysis. Progression to acute myeloid leukemia was independently influenced only by the cytogenetic risk category (p00.022). This study confirmed increased MVD in MDS. It does not support an independent prognostic role of angiogenesis in MDS.
C1 [Savic, Aleksandar] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
[Cemerikic-Martinovic, Vesna] Pathohistology Laboratory Beolab, Resavska 60, 11000 Belgrade, Serbia.
[Dovat, Sinisa] Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Children’s Hospital, Department of Pediatrics, H085, Division of Pediatric Hematology/Oncology, 500 University Drive, 17033 Hershey, PA, USA.
[Rajic, Nebojsa] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
[Urosevic, Ivana] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
[Sekulic, Borivoj] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
[Kvrgic, Vanja] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
[Popovic, Stevan] Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, Hajduk Veljkova 1-3, 21000 Novi Sad, Serbia.
RP Savic, A (reprint author), Clinical Center of Vojvodina, Faculty of Medicine, Clinic of Hematology, 21000 Novi Sad, Serbia.
EM asavic@uns.ac.rs
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Horny HP, Sotlar K, Valent P, 2007, Diagnostic value of histology and immunohistochemistry in myelodysplastic syndromes. Leuk Res 31:1609–1616
Valent P, Horny HP, Bennett JM et al, 2007, Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 31:727–736
Patsouris E, Katsarou O, Korkolopoulou P et al, 2004, Increased microvascular network in bone marrow of HIV-positive haemophilic patients. HIV Med 5:18–25
List A, Dewald G, Bennett J et al, 2006, Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456–1465
Raza A, Reeves JA, Feldman EJ et al, 2008, Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate- 1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 111:86–93
Musto P, 2004, Thalidomide therapy for myelodysplastic syndromes: current status and future perspectives. Leuk Res 28:325– 332
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Oh ST, Gotlib J, 2008, Antiangiogenic therapy in myelodysplastic syndromes: is there a role? Curr Hematol Malig Rep 3:10–18
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 681
EP 690
DI 10.1007/s12253-012-9495-y
PG 10
ER
PT J
AU Ziadi, S
Boughamoura, H
Ben Maitig, M
Ben Gacem, R
Mestiri, S
Chaabani, L
Trimeche, M
AF Ziadi, Sonia
Boughamoura, Hatem
Ben Maitig, Mahmoud
Ben Gacem, Riadh
Mestiri, Sarra
Chaabani, Lotfi
Trimeche, Mounir
TI Immunodetection of SV40 T/t-antigens in Human Osteosrcoma in a Series of Tunisian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Simian Virus 40; Immunohistochemistry; Tunisia
ID Osteosarcoma; Simian Virus 40; Immunohistochemistry; Tunisia
AB Osteosarcoma is a primary bone malignancy that typically occurs during adolescence but also has a second incidence peak in the elderly. The etiology of osteosarcoma is not well understood. Recent investigations have identified SV40 DNA sequences in osteosarcomas, suggesting that SV40 may contribute to tumor development. However, these studies also demonstrated geographical differences in SV40-positive osteosarcomas. The purpose of this study was to determine the prevalence and clinicopathological characteristics of SV40 positive osteosarcoma in Tunisian patients. Fifty-six formalin-fixed paraffin-embedded specimens of osteosarcomas were retrospectively investigated. Samples investigated were clinical cases examined between 1990 and 2004 in the Laboratory of Pathology at the University Hospital Farhat-Hached of Sousse (Tunisia). The search for SV40 was performed by immunohistochemistry using the Pab108 antibody for the detection of the viral oncoproteins: large T antigen and small t antigen (T/t-ag). SV40 status was correlated with clinico-pathological data. T/t-ag immunostaning was detected in the tumor cells in 31/56 (55.4%) osteosarcoma cases. SV40 positivity was more frequent (83%) in patients older than 40 years (5/6 cases) than in patients under 40 years (52%, 26/50), but the difference does not reach statistical significance (p00.33). Moreover, the time between the onset of clinical symptoms and diagnosis was shorter for SV40 positive than SV40 negative cases (p00.08). However, the viral status did not differ significantly according to gender, tumor size, histological subtype, tumor location, or metastases. This study documents the presence SV40 T/t-antigens in a proportion of osteosarcomas in Tunisian patients. The expression of these viral oncoproteins supports the hypothesis that SV40 may have a role in the pathogenesis of this tumor.
C1 [Ziadi, Sonia] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Boughamoura, Hatem] Sahloul Hospital, Department of OrthopedicsSousse, Tunisia.
[Ben Maitig, Mahmoud] Sahloul Hospital, Department of OrthopedicsSousse, Tunisia.
[Ben Gacem, Riadh] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Mestiri, Sarra] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Chaabani, Lotfi] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Trimeche, Mounir] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
RP Trimeche, M (reprint author), Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
EM m_trimech@yahoo.fr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 691
EP 696
DI 10.1007/s12253-012-9496-x
PG 6
ER
PT J
AU Wang, L
Yang, M
Shan, L
Qi, L
Chai, C
Zhou, Q
Yao, K
Wu, H
Sun, W
AF Wang, Lifeng
Yang, Miling
Shan, Lihui
Qi, Lei
Chai, Cuicui
Zhou, Qiufeng
Yao, Ke
Wu, Hongmei
Sun, Wenguang
TI The Role of SPARC Protein Expression in the Progress of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; SPARC; Angiogenesis; Cancer cells proliferation
ID Gastric cancer; SPARC; Angiogenesis; Cancer cells proliferation
AB We aimed to investigate the expression of SPARC (secreted protein, acidic and rich in cysteine) in gastric cancer and its relationship with tumor angiogenesis and cancer cells proliferation. Protein expression of SPARC, VEGF, CD34 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue was evaluated by immunohistochemistry. CD34 staining was used as an indicator of microvessel density (MVD). Ki-67 labeling Index (LI) indicated cancer cells proliferation. Statistical analysis was used to investigate its relationship with clinical characteristics, tumor angiogenesis and cancer cells proliferation. SPARC expression was mainly in the stromal cells surrounding the gastric cancer cells, and was statistically significant differences between gastric cancer and normal gastric tissue (P<0.05). Both the expression of SPARC and VEGF were related to differentiation degree, clinical stage, Lauren classification and lymph node metastasis (P<0.05). Expression of SPARC was significantly negatively correlated with the expression of VEGF and MVD in gastric cancer tissues. Expression of SPARC was also negatively correlated with Ki-67-LI. Our findings suggest that both the expression of SPARC and VEGF are closed to tumor angiogenesis in gastric cancer, SPARC inhibited tumor angiogenesis but VEGF promoted tumor angiogenesis. SPARC also inhibited cells proliferation of gastric cancer.
C1 [Wang, Lifeng] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Yang, Miling] The First Teaching Hospital, Zhengzhou University, Department of Pathology, 450003 Henan, China.
[Shan, Lihui] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Qi, Lei] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Chai, Cuicui] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Zhou, Qiufeng] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Yao, Ke] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Wu, Hongmei] The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
[Sun, Wenguang] The First Clinical College of Harbin Medical University, Department of Nutrition, 150001 Harbin, China.
RP Wang, L (reprint author), The First Clinical College of Harbin Medical University, Department of Pathology, 150001 Harbin, China.
EM hljwlf@yahoo.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 697
EP 702
DI 10.1007/s12253-012-9497-9
PG 6
ER
PT J
AU Livide, G
Epistolato, CM
Amenduni, M
Disciglio, V
Marozza, A
Mencarelli, AM
Toti, P
Lazzi, S
Hadjistilianou, Th
De Francesco, S
D’Ambrosio, A
Renieri, A
Ariani, F
AF Livide, Gabriella
Epistolato, Carmela Maria
Amenduni, Mariangela
Disciglio, Vittoria
Marozza, Annabella
Mencarelli, Antonietta Maria
Toti, Paolo
Lazzi, Stefano
Hadjistilianou, Theodora
De Francesco, Sonia
D’Ambrosio, Alfonso
Renieri, Alessandra
Ariani, Francesca
TI Epigenetic and Copy Number Variation Analysis in Retinoblastoma by MS-MLPA
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Retinoblastoma; MS-MLPA; Epigenetics; Copy number changes
ID Retinoblastoma; MS-MLPA; Epigenetics; Copy number changes
AB Retinoblastoma is the most common primary intraocular malignancy in children. Two step inactivation of RB1 (M1-M2) represents the key event in the pathogenesis of retinoblastoma but additional genetic and epigenetic events (M3-Mn) are required for tumor development. In the present study, we employed Methylation Specific Multiplex Ligation Probe Assay to investigate methylation status and copy number changes of 25 and 39 oncosuppressor genes, respectively. This technique was applied to analyse 12 retinoblastomas (5 bilateral and 7 unilateral) and results were compared to corresponding normal retina. We identified hypermethylation in seven new genes: MSH6 (50%), CD44 (42%), PAX5 (42%), GATA5 (25%), TP53 (8%), VHL (8%) and GSTP1 (8%) and we confirmed the previously reported hypermethylation of MGMT (58%), RB1 (17%) and CDKN2 (8%). These genes belong to key pathways including DNA repair, pRB and p53 signalling, transcriptional regulation, protein degradation, cell-cell interaction, cellular adhesion and migration. In the same group of retinoblastomas, a total of 29 copy number changes (19 duplications and 10 deletions) have been identified. Interestingly, we found deletions of the following oncosuppressor genes that might contribute to drive retinoblastoma tumorigenesis: TP53, CDH13, GATA5, CHFR, TP73 and IGSF4. The present data highlight the importance of epigenetic changes in retinoblastoma and indicate seven hypermethylated oncosuppressors never associated before to retinoblastoma pathogenesis. This study also confirms the presence of copy number variations in retinoblastoma, expecially in unilateral cases (mean 3 ±1.3) where these changes were found more frequently respect to bilateral cases (mean 1.4±1.1).
C1 [Livide, Gabriella] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Epistolato, Carmela Maria] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Amenduni, Mariangela] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Disciglio, Vittoria] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Marozza, Annabella] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Mencarelli, Antonietta Maria] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Toti, Paolo] University of Siena, Department of Human Pathology and Oncology, Section of PathologySiena, Italy.
[Lazzi, Stefano] University of Siena, Department of Human Pathology and Oncology, Section of PathologySiena, Italy.
[Hadjistilianou, Theodora] Azienda Ospedaliera Universitaria Senese, Ophthalmological Science and NeuroscienceSiena, Italy.
[De Francesco, Sonia] Azienda Ospedaliera Universitaria Senese, Ophthalmological Science and NeuroscienceSiena, Italy.
[D’Ambrosio, Alfonso] University of Siena, Pediatrics DepartmentSiena, Italy.
[Renieri, Alessandra] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
[Ariani, Francesca] University of Siena, Department of Biotechnology, Medical GeneticsSiena, Italy.
RP Renieri, A (reprint author), University of Siena, Department of Biotechnology, Medical Genetics, Siena, Italy.
EM renieri@unisi.it
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 703
EP 712
DI 10.1007/s12253-012-9498-8
PG 10
ER
PT J
AU Jin, JSh
Tsao, TY
Sun, PCh
Yu, ChP
Tzao, Ch
AF Jin, Jong-Shiaw
Tsao, Tang-Yi
Sun, Pei-Chang
Yu, Cheng-Ping
Tzao, Ching
TI SAHA Inhibits the Growth of Colon Tumors by Decreasing Histone Deacetylase and the Expression of Cyclin D1 and Survivin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Histone deacetylase; Histone deacetylase inhibitor; Nude mice; Colon cancer
ID Histone deacetylase; Histone deacetylase inhibitor; Nude mice; Colon cancer
AB We studied the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on colon cancer. The expression of HDACs in colorectal cancer specimens and the effects of SAHA on colon cancer cells and tumors of nude mice were assessed. Treatment with SAHA (3 μm) for 72 h induced downregulation of different subtypes of HDAC proteins and also induced acetylation of histone 3 and histone 4. SAHA significantly inhibited the expression of the oncogenic protein c-myc and also increased the expression of the p53 and Rb proteins. The immunohistochemical staining of HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, was significantly increased in colorectal adenocarcinoma specimens compared to healthy control tissues. In addition, murine studies showed that 100 mg/kg SAHA administered by intraperitoneal injection significantly induced tumor necrosis and inhibited the growth of colon tumors. Immunohistochemistry of the tumor tissues from nude mice revealed that SAHA inhibited the expression of different subtypes of histone deacetylase, the anti-apoptotic proteins cyclin D1, survivin, and also inhibited cell proliferative as determined by Ki67 expression. SAHA inhibited the growth of colon tumors by decreasing histone deacetylases and the expression of cyclin D1 and survivin in nude mice.
C1 [Jin, Jong-Shiaw] Tungs’ Taichung Metro Harbor Hospital, Department of PathologyWuqi Township, Taichung County, Taiwan, Republic of China.
[Tsao, Tang-Yi] Tungs’ Taichung Metro Harbor Hospital, Department of PathologyWuqi Township, Taichung County, Taiwan, Republic of China.
[Sun, Pei-Chang] National Defense Medical Center, Tri-Service General Hospital, Department of PathologyNeihu, Taipei County, Taiwan, Republic of China.
[Yu, Cheng-Ping] National Defense Medical Center, Tri-Service General Hospital, Department of PathologyNeihu, Taipei County, Taiwan, Republic of China.
[Tzao, Ching] National Defense Medical Center, Tri-Service General Hospital, Division of Thoracic Surgery, Department of Surgery, No. 325, Sec. 2, Cheng-Kung Road, 114 Neihu, Taipei County, Taiwan, Republic of China.
RP Tzao, Ch (reprint author), National Defense Medical Center, Tri-Service General Hospital, Division of Thoracic Surgery, Department of Surgery, 114 Neihu, Taiwan, Republic of China.
EM doctor.jsjin@gmail.com
CR Mayer RJ, 2009, Targeted therapy for advanced colorectal cancermore is not always better. N Eng J Med 360:623–625
WilkoW, Annika R, Silvia N, Aurelia N, Ann-Christin B, Manfred D, Volker G, Boehm M, Thomas B, Carsten D, 2008, Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res 14:1669–1677
Ito K, Adcock IM, 2002, Histone acetylation and histone deacetylation. Mol Biotechnol 20:99–106
Kuo MH, Allis CD, 1998, Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20:615–626
Kim DH, Kim M, Kwon HJ, 2003, Histone deacetylase in carcinogenesis and its inhibitors as anti-cancer agents. J Biochem Mol Biol 36:110–119
Marks PA, Richon VM, Breslow R, Rifkind RA, 2001, Histone deacetylase inhibitors as new cancer drugs. Curr Opin Oncol 13:477–483
Luong QT, O’Kelly J, Braunstein GD, Hershman JM, Koeffler HP, 2006, Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo. Clin Cancer Res 12:5570–5577
Sun PC, Tzao C, Chen BH, Liu CW, Yu CP, Jin JS, 2010, Suberoylanilide hydroxamic acid induces apoptosis and sub-G1 arrest of 320 HSR colon cancer cells. J Biochem Sci 17:76–85
Jin JS, Hsieh DS, Loh SH, Chen A, Yao CW, Yen CY, 2006, Increasing expression of serine protease matriptase in ovary tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters. Mod Pathol 19:447–452
Jin JS, Wu WY, Lin YF, 2006, Higher expression of epidermal growth factor receptor is associated with extracellular matrix metalloprotease inducer in colorectal adenocarcinoma: tissue microarray analysis of immunostaining score with clinicopathological parameters. Dis Markers 22:309–316
Jung M, 2001, Inhibitors of histone deacetylase as new anticancer agents. Curr Med Chem 8:1505–1511
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Kelly WK, O’Connor OA, Krug LM, 2005, Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol 23:3923– 3931
Sakajiri S, Kumagai T, Kawamata N, Saitoh T, Said JW, Koeffler HP, 2005, Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines. Exp Hematol 33:53–61
Bali P, Pranpat M, Swaby R, 2005, Activity of suberoylanilide hydroxamic acid against human breast cancer cells with amplification of Her-2. Clin Cancer Res 11:6382–6389
Rundall BK, Denlinger CE, Jones DR, 2005, Suberoylanilide hydroxamic acid combined with gemcitabine enhances apoptosis in non-small cell lung cancer. Surgery 138:360–367
Takai N, Desmond JC, Kumagai T, 2004, Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin Cancer Res 10:1141–1149
Takai N, Kawamata N, Gui D, Said JW, Miyakawa I, Koeffler HP, 2004, Human ovarian carcinoma cells: histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer 101:2760–2770
Altieri DC, 2006, The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr Opin Cell Biol 18:609–615
Noh EJ, Lim DS, Jeong G, Lee JS, 2009, An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner. Biochem Biophys Res Commun 378:326–331
Kim DH, Kundu JK, Surh YJ, 2011, Redox modulation of p53: mechanisms and functional significance. Mol Carcinog 50:222– 234
Shen F, Kirmani KZ, Xiao Z, Thirlby BH, Hickey RJ, Malkas LH, 2011, Nuclear protein isoforms: implications for cancer diagnosis and therapy. J Cell Biochem 112:756–760
Smith RA, Tang J, Tudur-Smith C, Neoptolemos JP, Ghaneh P, 2011, Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer. Br J Cancer 104:1440–1451
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 713
EP 720
DI 10.1007/s12253-012-9499-7
PG 8
ER
PT J
AU Krzeslak, A
Wojcik-Krowiranda, K
Forma, E
Jozwiak, P
Romanowicz, H
Bienkiewicz, A
Brys, M
AF Krzeslak, Anna
Wojcik-Krowiranda, Katarzyna
Forma, Ewa
Jozwiak, Pawel
Romanowicz, Hanna
Bienkiewicz, Andrzej
Brys, Magdalena
TI Expression of GLUT1 and GLUT3 Glucose Transporters in Endometrial and Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glucose transporters; mRNA expression; Protein expression; Breast cancer; Endometrial cancer
ID Glucose transporters; mRNA expression; Protein expression; Breast cancer; Endometrial cancer
AB Cancer cells have accelerated metabolism and high glucose requirements. The up-regulation of specific glucose transporters may represent a key mechanism by which malignant cells may achieve increased glucose uptake to support the high rate of glycolysis. In present study we analyzed the mRNA and protein expression of GLUT1 and GLUT3 glucose transporters by quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting technique in 76 cases of endometrial carcinoma and 70 cases of breast carcinoma. SLC2A1 and SLCA2A3 mRNAs expression was found, respectively in 100% and 97.4% samples of endometrial cancers and only in 50% and 40% samples of breast cancers. In endometrial cancers GLUT1 and GLUT3 protein expression was identified in 67.1% and 30.3% of cases. Analogously, in breast cancers in 48.7% and 21% of samples, respectively. The results showed that both endometrial and breast poorly differentiated tumors (grade 2 and 3) had significantly higher GLUT1 and GLUT3 expression than well-differentiated tumors (grade 1). Statistically significant association was found between SLCA2A3 mRNA expression and estrogen and progesterone receptors status in breast cancers. GLUT1 has been reported to be involved in the uptake of glucose by endometrial and breast carcinoma cells earlier and the present study determined that GLUT3 expression is also involved. GLUT1 and GLUT3 seem to be important markers in endometrial and breast tumors differentiation.
C1 [Krzeslak, Anna] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Wojcik-Krowiranda, Katarzyna] Medical University of Lodz, Department of Gynecological Oncology, Pabianicka 62, 93-509 Lodz, Poland.
[Forma, Ewa] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Jozwiak, Pawel] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Rzgowska 281/289, 93-338 Lodz, Poland.
[Bienkiewicz, Andrzej] Medical University of Lodz, Department of Gynecological Oncology, Pabianicka 62, 93-509 Lodz, Poland.
[Brys, Magdalena] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
RP Brys, M (reprint author), Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, 90-236 Lodz, Poland.
EM zreg@biol.uni.lodz.pl
CR Young CD, Anderson SM, 2008, Sugar and fat—that’s where it’s at: metabolic changes in tumors. Breast Cancer Res 10:202
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Rivenzon-Segal D, Boldin-Adamsky S, Seger D, Seger R, Degani H, 2003, Glycolysis and glucose transporter 1 as markers of response to hormonal therapy in breast cancer. Int J Cancer 107:177–182
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 721
EP 728
DI 10.1007/s12253-012-9500-5
PG 8
ER
PT J
AU Gasparinho, GM
Morgado, S
Fonseca, R
Chaves, P
AF Gasparinho, Gabriela Maria
Morgado, Sonia
Fonseca, Ricardo
Chaves, Paula
TI Collision Metastases of Breast and Rectal Carcinoma – A Possible Role for Chemokines Receptors Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Gasparinho, Gabriela Maria] Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Servico de Anatomia Patologica, Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal.
[Morgado, Sonia] Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Servico de Anatomia Patologica, Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal.
[Fonseca, Ricardo] Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Servico de Anatomia Patologica, Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal.
[Chaves, Paula] Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Servico de Anatomia Patologica, Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal.
RP Gasparinho, GM (reprint author), Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Servico de Anatomia Patologica, 1099-023 Lisbon, Portugal.
EM mggasparinho@gmail.com
CR Sughayer MA, Zakarneh L, Abu-Shakra R, 2009, Collision metastasis of breast and ovarian adenocarcinoma in axillary lymph nodes: a case report and review of the literature. Pathol Oncol Res 15:423–427
Mattioli F, Masoni F, Ponti G, Rossi G, Molteni G, Alicandri- Ciufelli M, Presutti L, 2009, “Collision” metastasis from unknown primary squamous cell carcinoma and papillary microcarcinoma of thyroid presenting as lateral cervical cystic mass. Auris Nasus Larynx 36:372–375
Raman D, Baugher PJ, Thu YM, Richmond A, 2007, Minireview: role of chemokines in tumor growth. Cancer Lett 256:137–165
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegul E, Zlotnik A, 2001, Involvement of chemokine receptors in breast cancer metastases. Nature 410:50– 56
Kodama J, Hasengaowa KT, Seki N, Matsuo T, Ojima Y, Nakamura K, Hongo A, Hiramatsu Y, 2007, Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer. Ann Oncol 18:70–76
Andre F, Cabioglu N, Assi H, Sabourin JC, Delaloge S, Sahin A, Broglio K, Spano JP, Combadiere C, Bucana C, Soria JC, Cristofanilli M, 2006, Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer. Ann Oncol 17:945–951
Mizell J, Smith M, Li BDL, Ampli F, Chu QD, 2009, Overexpression of CXCR4 in primary tumor of patients with Her2- negative breast cancer was predictive of a poor disease-free survival: a validation study. Ann Surg Oncol 16:2711–2716
Mburu YK, Wang J, Wood MA, Walker WH, Ferris RL, 2006, CCR7 mediates inflammation-associated tumor progression. Immunol Res 36:61–72
Ghadjar P, Coupland SE, Na IK, Noutsias M, Letsch A, Stroux A, Bauer S, Buhr HJ, Thiel E, Scheibenbogen C, Keilholz U, 2006, Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer. J Clin Oncol 24:1910–1916
Ghadjar P, Rubie C, Aebersold DM, Keilholz U, 2009, Minireview: the chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer. Int J Cancer 125:741–745
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 729
EP 732
DI 10.1007/s12253-011-9443-2
PG 4
ER
PT J
AU Kulcsar, I
Szanto, A
Varoczy, L
Mehes, G
Zeher, M
AF Kulcsar, Istvan
Szanto, Antonia
Varoczy, Laszlo
Mehes, Gabor
Zeher, Margit
TI Hodgkin’s Lymphoma Developed after Autologous Stem Cell Transplantation for Multiple Myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Kulcsar, Istvan] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Szanto, Antonia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Zeher, Margit] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
RP Kulcsar, I (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
EM istvankulcsar@yahoo.com
CR Curtis RE, Travis LB, Rowlings PA, et al., 1999, Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 94: 2208±2216.
Lowe T, Bhatia S, Somlo G, 2007, Second malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 13(10):1121–1134
Gy V, Sebestyen A, Jaray J, Kopper L, 2008, Malignant tumors in the immunocompromised state following organ transplantation. Orvoskepzes 81:235–242
Fend F, Martinez A, Quintanilla-Martinez L et al, 2002, Clonally unrelated Hodgkin’s disease following autologous stem cell transplant for B-cell lymphoma. Br J Haematol 116, 2):329–333
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Rowlings PA, Curtis RE, Passweg JR et al, 1999, Increased incidence of Hodgkin’s disease after allogeneic bone marrow transplantation. J Clin Oncol 17(10):3122–3127
Ranganathan S, Webber S, Ahuja S, Jaffe R, 2004, Hodgkin-like posttransplant lymphoproliferative disorder in children: does it differ from posttransplant Hodgkin lymphoma? Pediatr Dev Pathol 7(4):348–360
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 733
EP 736
DI 10.1007/s12253-011-9477-5
PG 4
ER
PT J
AU Payer, E
Miltenyi, Zs
Simon, Zs
Szabados, L
Hegyi, K
Mehes, G
Illes,
AF Payer, Edit
Miltenyi, Zsofia
Simon, Zsofia
Szabados, Lajos
Hegyi, Katalin
Mehes, Gabor
Illes, Arpad
TI Uncommon Late Relapse of Angioimmunoblastic T-Cell Lymphoma after 16-Year Remission Period
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Payer, Edit] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Simon, Zsofia] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
[Szabados, Lajos] Scanomed Kft., Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hegyi, Katalin] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Illes, Arpad] University of Debrecen, Medical and Health Center, 3rd Department of Medicine, Moricz Zs. krt. 22, 4032 Debrecen, Hungary.
RP Payer, E (reprint author), University of Debrecen, Medical and Health Center, 3rd Department of Medicine, 4032 Debrecen, Hungary.
EM payeredit@vipmail.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2012
VL 18
IS 3
BP 737
EP 741
DI 10.1007/s12253-011-9475-7
PG 5
ER
PT J
AU Kopper, L
AF Kopper, Laszlo
TI Denosumab—A Powerful RANKL Inhibitor to Stop Lytic Metastases and Other Bone Loss Actions by Osteoclasts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Denosumab; RANKL-inhibitor; Osteoclasts; Metastasis
ID Denosumab; RANKL-inhibitor; Osteoclasts; Metastasis
AB Denosumab is a perfect example on the targeted anticancer therapy. The inhibition of RANKL activity suppressed the osteoclasts’ resorptive function and so prevented skeletal related events. This effect is useful not only against bone metastases, but also in the treatment of other diseases caused by bone loss. In different solid tumors with bone metastasis the quality of life also improved, although the overall survival usually showed no change. On the market the main competitors for denosumab are still the bisphosphonates (questions of costs and reimbursement are not discussed) and some potential new agents e.g. Src kinases (as dasatinib, saracatinib, bosutinib), cathepsin K inhibitors, (e.g. odanacatib), and new selective estrogen receptor modulators (e.g. bazedoxifene, lasofoxifene). Nevertheless, today denosumab is one of the most powerful agents in bone-saving area.
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM kopper@korb1.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 743
EP 747
DI 10.1007/s12253-012-9538-4
PG 5
ER
PT J
AU Jokai, H
Marschalko, M
Csomor, J
Szakonyi, J
Kontar, O
Barna, G
Karpati, S
Hollo, P
AF Jokai, Hajnalka
Marschalko, Marta
Csomor, Judit
Szakonyi, Jozsef
Kontar, Orsolya
Barna, Gabor
Karpati, Sarolta
Hollo, Peter
TI Tissue-Specific Homing of Immune Cells in Malignant Skin Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Lymphocyte homing receptors; Cutaneous lymphocyte associated antigen; Malignant melanoma; Basal cell carcinoma; Squamous cell carcinoma; Cutaneous T-cell lymphoma
ID Lymphocyte homing receptors; Cutaneous lymphocyte associated antigen; Malignant melanoma; Basal cell carcinoma; Squamous cell carcinoma; Cutaneous T-cell lymphoma
AB Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral nonlymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by nonlymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sezary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.
C1 [Jokai, Hajnalka] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
[Marschalko, Marta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Szakonyi, Jozsef] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
[Kontar, Orsolya] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
[Hollo, Peter] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria u. 41, 1085 Budapest, Hungary.
RP Jokai, H (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM jokaihajnalka@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 749
EP 759
DI 10.1007/s12253-012-9529-5
PG 11
ER
PT J
AU Hegyi, K
Mehes, G
AF Hegyi, Katalin
Mehes, Gabor
TI Mitotic Failures in Cancer: Aurora B Kinase and its Potential Role in the Development of Aneuploidy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cell division; Mitotic failure; Aurora kinase; Aneuploidy; Cancer progression
ID Cell division; Mitotic failure; Aurora kinase; Aneuploidy; Cancer progression
AB One of the basic requirements during the process of cell division is to maintain genetic integrity and ensure normal ploidy. The family of Aurora kinases, composed of Aurora A, B and C, takes a major role in the control of centrosome cycle, mitotic entry, chromosome condensation and coordination of chromosomal movements. Deregulation of kinase expression was described in a series of different malignancies which was also associated with aneuploidy. Recently, Aurora kinases gained significant interest as potential therapeutic targets in oncology. While there is increasing evidence about the activities of Aurora A kinase during cancer progression, data are controversial regarding the role of Aurora B. In this review the biology of Aurora kinases and its potential relation to cancer progression is discussed with special focus on functional changes and determination of Aurora B kinase.
C1 [Hegyi, Katalin] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Mehes, G (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, 4032 Debrecen, Hungary.
EM gabor.mehes@dote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 761
EP 769
DI 10.1007/s12253-012-9534-8
PG 9
ER
PT J
AU Zeyaullah, M
Patro, M
Ahmad, I
Ibraheem, K
Sultan, P
Nehal, M
Ali, A
AF Zeyaullah, M
Patro, Mohan
Ahmad, Irfan
Ibraheem, Kawthar
Sultan, P
Nehal, Mohammad
Ali, Arif
TI Oncolytic Viruses in the Treatment of Cancer: A Review of Current Strategies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Oncolytic viruses; Tumor cells; Human cancer; Virotherapeutics; Combination therapy
ID Oncolytic viruses; Tumor cells; Human cancer; Virotherapeutics; Combination therapy
AB Oncolytic viruses are live, replication-competent viruses that replicate selectively in tumor cells leading to the destruction of the tumor cells. Tumor-selective replicating viruses offer appealing advantages over conventional cancer therapy and are promising a new approach for the treatment of human cancer. The development of virotherapeutics is based on several strategies. Virotherapy is not a new concept, but recent technical advances in the genetic modification of oncolytic viruses have improved their tumor specificity, leading to the development of new weapons for the war against cancer. Clinical trials with oncolytic viruses demonstrate the safety and feasibility of an effective virotherapeutic approach. Strategies to overcome potential obstacles and challenges to virotherapy are currently being explored. Systemic administrations of oncolytic viruses will successfully extend novel treatment against a range of tumors. Combination therapy has shown some encouraging antitumor responses by eliciting strong immunity against established cancer.
C1 [Zeyaullah, M] Omar Al-Mukhtar University, Faculty of Medicine, Department of MicrobiologyAl-Baida, Libyan Arab Jamabiriya.
[Patro, Mohan] Omar Al-Mukhtar University, Faculty of Medicine, Department of SurgeryAl-Baida, Libyan Arab Jamabiriya.
[Ahmad, Irfan] Jamia Millia Islamia, Department of Biosciences, 110025 New Delhi, India.
[Ibraheem, Kawthar] Omar Al-Mukhtar University, Faculty of Medicine, Department of MicrobiologyAl-Baida, Libyan Arab Jamabiriya.
[Sultan, P] Omar Al-Mukhtar University, Faculty of Medicine, Department of BiochemistryAl-Baida, Libyan Arab Jamabiriya.
[Nehal, Mohammad] Central University of Bihar (CUB)Patna, Bihar, India.
[Ali, Arif] Jamia Millia Islamia (Central University), Department of Biotechnology, 110025 New Delhi, India.
RP Zeyaullah, M (reprint author), Omar Al-Mukhtar University, Faculty of Medicine, Department of Microbiology, Al-Baida, Libyan Arab Jamabiriya.
EM zeya786@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 771
EP 781
DI 10.1007/s12253-012-9548-2
PG 11
ER
PT J
AU Omar, FMM
Ito, K
Nga, EM
Soo, R
Peh, KB
Ismail, MT
Thakkar, B
Soong, R
Ito, Y
Salto-Tellez, M
AF Omar, Feroz Mohd Mohd
Ito, Kosei
Nga, En Min
Soo, Ross
Peh, Keow Bee
Ismail, Muliana Tuty
Thakkar, Bhavin
Soong, Richie
Ito, Yoshiaki
Salto-Tellez, Manuel
TI RUNX3 Downregulation in Human Lung Adenocarcinoma is Independent of p53, EGFR or KRAS Status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; KRAS; Lung adenocarcinoma; p53; Promoter hypermethylation; RUNX3
ID EGFR; KRAS; Lung adenocarcinoma; p53; Promoter hypermethylation; RUNX3
AB RUNX3 aberrations play a pivotal role in the oncogenesis of breast, gastric, colon, skin and lung tissues. The aim of this study was to characterize further the expression of RUNX3 in lung cancers. To achieve this, a lung cancer tissue microarray (TMA), frozen lung cancer tissues and lung cell lines were examined for RUNX3 expression by immunohistochemistry, while the TMA was also examined for EGFR and p53 expression. RUNX3 promoter methylation status, and EGFR and KRAS mutation status were also investigated. Inactivation of RUNX3 was observed in 70% of the adenocarcinoma samples, and this was associated with promoter hypermethylation but not biased to EGFR/KRAS mutations. Our results suggest a central role of RUNX3 downregulation in pulmonary adenocarcinoma, which may not be dependent of other established cancer-causing pathways and may have important diagnostic and screening implications.
C1 [Omar, Feroz Mohd Mohd] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Ito, Kosei] Nagasaki University, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523 Nagasaki, Japan.
[Nga, En Min] National University Hospital, Department of Pathology, 5, Lower Kent Ridge Road, 119074 Singapore, Singapore.
[Soo, Ross] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Peh, Keow Bee] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Ismail, Muliana Tuty] National University Hospital, Department of Pathology, 5, Lower Kent Ridge Road, 119074 Singapore, Singapore.
[Thakkar, Bhavin] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Soong, Richie] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Ito, Yoshiaki] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
[Salto-Tellez, Manuel] National University of Singapore, Cancer Science Institute of Singapore, #12-01, 14 Medical Drive, 117599 Singapore, Singapore.
RP Ito, Y (reprint author), National University of Singapore, Cancer Science Institute of Singapore, 117599 Singapore, Singapore.
EM csiitoy@nus.edu.sg
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Ibrahim AEK, Arends MJ, Silva A-L, Wyllie AH, Greger L, Ito Y et al, 2010, Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut
Soung YH, Lee JW, Kim SY, Seo SH, Park WS, Nam SW et al, 2005, Mutational analysis of EGFR and K-RAS genes in lung adenocarcinomas. Virchows Arch 446(5):483–488
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 783
EP 792
DI 10.1007/s12253-011-9485-5
PG 10
ER
PT J
AU Calabuig-Farinas, S
Benso, GR
Szuhai, K
Machado, I
Lopez-Guerrero, AJ
de Jong, D
Peydro, A
San Miguel, T
Navarro, L
Pellin, A
LLombart-Bosch, A
AF Calabuig-Farinas, Silvia
Benso, Gil Rosario
Szuhai, Karoly
Machado, Isidro
Lopez-Guerrero, Antonio Jose
de Jong, Danielle
Peydro, Amando
San Miguel, Teresa
Navarro, Lara
Pellin, Antonio
LLombart-Bosch, Antonio
TI Characterization of a New Human Cell Line (CH-3573) Derived from a Grade II Chondrosarcoma with Matrix Production
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone tumor; Cell line; Chondrosarcoma; Grade II; Karyotype; Matrix
ID Bone tumor; Cell line; Chondrosarcoma; Grade II; Karyotype; Matrix
AB Chondrosarcomas are malignant cartilageforming tumors that represent the third most common malignant solid tumor of bone. In patients with grades II and III, local recurrence, increasing tumor size and dedifferentiation have been associated with lower survival rates. These biologically poorly-understood neoplasms vary considerably in clinical presentation and biological behavior. Cytogenetic studies have shown that heterogeneity is related to karyotypic complexity; moreover, alterations in the 9p21 locus and TP53 gene are related to disease progression. Despite the relatively high frequency of chondrosarcoma only a limited number of cell lines exist in the scientific community, limiting the possibility to study hypothesisderived research or primary drug interaction necessary for pre-clinical studies. We report a chondrosarcoma cell line, CH-3573, derived from a primary tumor that may serve as a useful tool for both in vitro and in vivo models to study the molecular pathogenesis. In addition, xenograft passages in nude mice were studied to characterize the genetic stability over the course of tumor progression. In contrary to other reported cell lines, an important feature of our established cell line was the retained matrix production, a characteristic feature of a conventional grade II chondrosarcoma. The cell line (CH-3573) was characterized by pathological, immunohistochemical and molecular genetic methods.
C1 [Calabuig-Farinas, Silvia] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[Benso, Gil Rosario] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[Szuhai, Karoly] Leiden University, Medical Center, Department of Molecular Cell BiologyLeiden, The Netherlands.
[Machado, Isidro] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[Lopez-Guerrero, Antonio Jose] Fundacion Instituto Valenciano de Oncologia, Laboratory of Molecular BiologyValencia, Spain.
[de Jong, Danielle] Leiden University, Medical Center, Department of Molecular Cell BiologyLeiden, The Netherlands.
[Peydro, Amando] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[San Miguel, Teresa] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[Navarro, Lara] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[Pellin, Antonio] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
[LLombart-Bosch, Antonio] University of Valencia, Department of Pathology, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain.
RP LLombart-Bosch, A (reprint author), University of Valencia, Department of Pathology, 46010 Valencia, Spain.
EM antonio.llombart@uv.es
CR Evans HL, Ayala AG, Romsdahl MM, 1977, Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40(2):818–31
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Puri A, Shah M, Agarwal MG, Jambhekar NA, Basappa P, 2009, Chondrosarcoma of bone: does the size of the tumor, the presence of a pathologic fracture, or prior intervention have an impact on local control and survival? J Cancer Res Ther 5(1):14–9
Riedel RF, Larrier N, Dodd L, Kirsch D, Martinez S, Brigman BE, 2009, The clinical management of chondrosarcoma. Curr Treat Options Oncol 10(1–2):94–106
Takigawa M, Tajima K, Pan HO et al, 1989, Establishment of a clonal human chondrosarcoma cell line with cartilage phenotypes. Cancer Res 49(14):3996–4002
Takigawa M, Pan HO, Kinoshita A, Tajima K, Takano Y, 1991, Establishment from a human chondrosarcoma of a new immortal cell line with high tumorigenicity in vivo, which is able to form proteoglycan-rich cartilage-like nodules and to respond to insulin in vitro. Int J Cancer 48(5):717–25
Ikemoto S, Sugimura K, Yoshida N, Nakatani T, 2004, Chondrosarcoma of the urinary bladder and establishment of a human chondrosarcoma cell line, OCUU-6). Hum Cell 17(3):93–6
Kudo N, Ogose A, Hotta T et al, 2007, Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation. Virchows Arch 451(3):691–9
Yang L, Chen Q, Zhang S, Wang X, Li W, Wen J et al, 2009, A novel mutated cell line with characteristics of dedifferentiated chondrosarcoma. Int J Mol Med 24(4):427–35
Gil-Benso R, Lopez-Gines C, Lopez-Guerrero JA et al, 2003, Establishment and characterization of a continuous human chondrosarcoma cell line, ch-2879: comparative histologic and genetic studies with its tumor of origin. Lab Invest 83(6):877–87
Kalinski T, Krueger S, Pelz AF et al, 2005, Establishment and characterization of the permanent human cell line C3842 derived from a secondary chondrosarcoma in Ollier’s disease. Virchows Arch 446(3):287–99
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Szuhai K, Tanke HJ, 2006, COBRA: combined binary ratio labeling of nucleic-acid probes for multi-color fluorescence in situ hybridization karyotyping. Nat Protoc 1(1):264–75
Lopez-Guerrero JA, Lopez-Gines C, Pellin A, Carda C, Llombart- Bosch A, 2004, Deregulation of the G1 to S-phase cell cycle checkpoint is involved in the pathogenesis of human osteosarcoma. Diagn Mol Pathol 13(2):81–91
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Moussavi-Harami F, Mollano A, Martin JA et al, 2006, Intrinsic radiation resistance in human chondrosarcoma cells. Biochem Biophys Res Commun 346(2):379–85
Rozeman LB, Hogendoorn PC, Bovee JV, 2002, Diagnosis and prognosis of chondrosarcoma of bone. Expert Rev Mol Diagn 2, 5):461–72
Bovee JV, van Royen M, Bardoel AF et al, 2000, Near-haploidy and subsequent polyploidization characterize the progression of peripheral chondrosarcoma. Am J Pathol 157(5):1587–95
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 793
EP 802
DI 10.1007/s12253-012-9505-0
PG 10
ER
PT J
AU Annunziata, C
Buonaguro, L
Buonaguro, MF
Tornesello, LM
AF Annunziata, Clorinda
Buonaguro, Luigi
Buonaguro, M Franco
Tornesello, Lina Maria
TI Characterization of the Human Papillomavirus (HPV) Integration Sites into Genital Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human Papillomavirus; HPV; Integration sites; Penile cancer; Vulvar Cancer
ID Human Papillomavirus; HPV; Integration sites; Penile cancer; Vulvar Cancer
AB Oncogenic HPVs have been found frequently integrated into human genome of invasive cancers and chromosomal localization has been extensively investigated in cervical carcinoma. Few studies have analyzed the HPV integration loci in other genital cancers. We have characterized the integration sites of HPV16 in invasive penile carcinoma by means of Alu-HPV-based PCR. Nucleotide sequence analysis of viral–human DNA junctions showed that HPV integration occurredin one case within the chromosome 8q21.3 region, in which the FAM92A1 gene is mapped, and in the second case inside the chromosome 16p13.3, within the intronic region of TRAP1 gene. These results confirm previous observations, summarized in a systematic review of the literature, on the HPV integration events in gene loci relevant to cancer pathogenesis.
C1 [Annunziata, Clorinda] National Cancer Institute, Molecular Biology and Viral Oncology and AIDS Reference Centre, Cappella Cangiani, 80131 Naples, Italy.
[Buonaguro, Luigi] National Cancer Institute, Molecular Biology and Viral Oncology and AIDS Reference Centre, Cappella Cangiani, 80131 Naples, Italy.
[Buonaguro, M Franco] National Cancer Institute, Molecular Biology and Viral Oncology and AIDS Reference Centre, Cappella Cangiani, 80131 Naples, Italy.
[Tornesello, Lina Maria] National Cancer Institute, Molecular Biology and Viral Oncology and AIDS Reference Centre, Cappella Cangiani, 80131 Naples, Italy.
RP Tornesello, LM (reprint author), National Cancer Institute, Molecular Biology and Viral Oncology and AIDS Reference Centre, 80131 Naples, Italy.
EM m.tornesello@istitutotumori.na.it;irccsvir@unina.it
CR Zur Hausen H, 2002, Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2(5):342–350
Bouvard V, Baan R, Straif K et al, 2009, A review of human carcinogens–Part B: biological agents. Lancet Oncol 10(4):321– 322
Parkin DM, Bray F, 2006, Chapter 2: The burden of HPV-related cancers. Vaccine 24(Suppl 3):S11–S25
Dunne EF, Nielson CM, Stone KM et al, 2006, Prevalence of HPV infection among men: A systematic review of the literature. J Infect Dis 194(8):1044–1057
Bruni L, Diaz M, Castellsague X et al, 2010, Cervical Human Papillomavirus Prevalence in 5 Continents: Meta-Analysis of 1 Million Women with Normal Cytological Findings. J Infect Dis.
Palefsky JM, 2007, HPV infection in men. Dis Markers 23, 4):261–272
Daling JR, Madeleine MM, Schwartz SM et al, 2002, A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84(2):263–270
Gillison ML, Shah KV, 2003, Chapter 9: Role of mucosal human papillomavirus in nongenital cancers. J Natl Cancer Inst Monogr, 31):57–65.
Smith JS, Backes DM, Hoots BE et al, 2009, Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol 113(4):917–924
Steenbergen RD, De WJ, Wilting SM et al, 2005, HPV-mediated transformation of the anogenital tract. J Clin Virol 32(Suppl 1): S25–S33
Wentzensen N, Vinokurova S, von Knebel DM, 2004, Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 64(11):3878–3884
Kraus I, Driesch C, Vinokurova S et al, 2008, The majority of viral-cellular fusion transcripts in cervical carcinomas cotranscribe cellular sequences of known or predicted genes. Cancer Res 68, 7):2514–2522
Matovina M, Sabol I, Grubisic G et al, 2009, Identification of human papillomavirus type 16 integration sites in high-grade precancerous cervical lesions. Gynecol Oncol 113(1):120–127
Couturier J, Sastre-Garau X, Schneider-Maunoury S et al, 1991, Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression. J Virol 65(8):4534–4538
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Tornesello ML, Buonaguro FM, Meglio A et al, 1997, Sequence variations and viral genomic state of human papillomavirus type 16 in penile carcinomas from Ugandan patients. J Gen Virol 78(Pt 9):2199–2208
Pett M, Coleman N, 2007, Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis? J Pathol 212, 4):356–367
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Kraus I, Driesch C, Vinokurova S et al, 2008, The majority of viral-cellular fusion transcripts in cervical carcinomas cotranscribe cellular sequences of known or predicted genes. Cancer Res 68, 7):2514–2522
Liu D, Hu J, Agorreta J et al, 2010, Tumor necrosis factor receptor-associated protein 1(TRAP1, regulates genes involved in cell cycle and metastases. Cancer Lett 296(2):194–205
Liang S, Gong F, Zhao X et al, 2009, Prokaryotic expression, purification of a new tumor-relative protein FAM92A1-289 and its characterization in renal cell carcinoma. Cancer Lett 276(1):81–87
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Liu D, Hu J, Agorreta J et al, 2010, Tumor necrosis factor receptor-associated protein 1(TRAP1, regulates genes involved in cell cycle and metastases. Cancer Lett 296(2):194–205
Nakanishi G, Fujii K, Asagoe K et al, 2009, Human papillomavirus genome integration in multifocal vulvar Bowen’s disease and squamous cell carcinoma. Clin Exp Dermatol 34, 8):e965–e967
Dall KL, Scarpini CG, Roberts I et al, 2008, Characterization of naturally occurring HPV16 integration sites isolated from cervical keratinocytes under noncompetitive conditions. Cancer Res 68, 20):8249–8259
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 803
EP 808
DI 10.1007/s12253-012-9507-y
PG 6
ER
PT J
AU Chen, M
Chen, Tsh
Lu, Yy
Liu, Chy
Qu, Jl
AF Chen, Min
Chen, Tong-sheng
Lu, Ying-ying
Liu, Cheng-yi
Qu, Jun-le
TI Dihydroarteminsin-Induced Apoptosis is not Dependent on the Translocation of Bim to the Endoplasmic Reticulum in Human Lung Adenocarcinoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bim; Dihydroartemisinin (DHA); Endoplasmic reticulum (ER); Apoptosis; Human lung adenocarcinoma cells
ID Bim; Dihydroartemisinin (DHA); Endoplasmic reticulum (ER); Apoptosis; Human lung adenocarcinoma cells
AB Bim, a proapoptotic BH3-only member of Bcl-2 family, has been considered to play an important role in initiating mitochondrial apoptotic pathway. Our previous studies have shown the ability of dihydroarteminsin (DHA) to induce apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. In this study, we investigated the function of Bim during DHA-induced apoptosis in ASTC-a-1 and another human lung adenocarcinoma (A549) cell lines. Confocal imaging of single living cell expressing GFP-BimL showed the translocation of Bim to endoplasmic reticulum (ER) rather than mitochondria during DHA-induced apoptosis.Moreover, we also found that DHA induced ER stress and an increase of Bim protein levels. However, silencing Bim by short hairpin RNA did not inhibit DHA-induced caspase-9 activation and cell apoptosis. Taken together, our results demonstrate for the first time that DHA induces Bim translocation to ER, but DHA-induced apoptosis is not dependent on Bim in ASTCa-1 and A549 cell lines.
C1 [Chen, Min] South China Normal University, MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, 510631 Guangzhou, China.
[Chen, Tong-sheng] South China Normal University, MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, 510631 Guangzhou, China.
[Lu, Ying-ying] South China Normal University, MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, 510631 Guangzhou, China.
[Liu, Cheng-yi] South China Normal University, Laboratory of Laser Sports Medicine, 510631 Guangzhou, China.
[Qu, Jun-le] Shenzhen University, Institute of Optoelectronics, 518060 Shenzhen, China.
RP Chen, Tsh (reprint author), South China Normal University, MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, 510631 Guangzhou, China.
EM chentsh@scnu.edu.cn
CR Wang XW, Xing D, Liu L et al, 2009, BimL directly neutralizes Bcl-xL to promote Bax activation during UV-induced apoptosis. FEBS Lett 583:1873–1879
Yin KJ, Hsu CY, Hu XY et al, 2006, Protein phosphatase 2A regulates bim expression via the Akt/FKHRL1 signaling pathway in amyloidpeptide-induced cerebrovascular endothelial cell death. J Neurosci 26:2290–2299
Schneiders UM, Schyschka L, Rudy A et al, 2009, BH3-only proteins Mcl-1 and Bim as well as endonuclease G are targeted in spongistatin 1–induced apoptosis in breast cancer cells. Mol Cancer Ther 8:2914–2925
Khawaja NR, Carre M, Kovacic H et al, 2008, Patupilone-induced apoptosis is mediated by mitochondrial reactive oxygen species through Bim relocalization to mitochondria. Mol Pharmacol 74:1072–1083
Szegezdi E, Logue SE, Gorman AM et al, 2006, Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:880–885
Merino D, Giam M, Hughes PD et al, 2009, The role of BH3-only protein Bim extends beyond inhibiting Bcl-2–like prosurvival proteins. J Cell Biol 186:355–362
Morishima N, Nakanishi K, Tsuchiya K et al, 2004, Translocation of Bim to the endoplasmic reticulum, ER, mediates ER stress signaling for activation of caspase-12 during ER stress-induced apoptosis. J Biol Chem 279:50375–50381
Puthalakath H, O’Reilly LA, Gunn P et al, 2007, ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129:1337– 1349
Chin TY, Lin HC, Kuo JP et al, 2007, Dual effect of thapsigargin on cell death in porcine aortic smooth muscle cells. Am J Physiolcell Ph 292:383–395
Morishima N, Nakanishi K, Takenouchi H et al, 2002, An endoplasmic reticulum stress-specific caspase cascade in apoptosis. J Biol Chem 277:34287–34294
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Handrick R, Ontikatze T, Bauer KD et al, 2010, Dihydroartemisinin induces apoptosis by a Bak-dependent intrinsic pathway. Mol Cancer Ther 9:2497–2510
Mercer AE, Maggs JL, Sun XM et al, 2007, Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J Biol Chem 282:9372–9382
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Zhang YJ, Xing D, Liu L, 2009, PUMA promotes Bax translocation by both directly interacting with Bax and by competitive binding to Bcl-XL during UV-induced apoptosis. Mol Biol Cell 20:3077–3087
Zhang WW, Wang ZP, Chen TS, 2010, Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells. Med Oncol 28:307–314
Stan SD, Hahm ER, Warin R et al, 2008, Withaferin A causes FOXO3a- and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res 68:7661–7669
Nakayama Y, Endo M, Tsukano H et al, 2010, Molecular mechanisms of the LPS-induced non-apoptotic ER stress-CHOP pathway. J Biochem 147:471–483
Lu JJ, Chen SM, Zhang XWet al, 2010, The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drug., DOI 10.1007/s10637-010-9481-8
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Kim H, Tu HC, Ren D et al, 2009, Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell 36:487–499
Gillissen B, Essmann F, Hemmati PG et al, 2007, Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis. J Cell Biol 179:701–715
Zhang LL, Zhang YJ, Xing D, 2010, LPLI inhibits apoptosis upstream of Bax translocation via a GSK-3β-inactivation mechanism. J Cell Physiol 224:218–228
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 809
EP 816
DI 10.1007/s12253-012-9508-x
PG 8
ER
PT J
AU Attaallah, W
Yilmaz, MA
Erdogan, N
Yalcin, S
Aktan, A
AF Attaallah, Wafi
Yilmaz, Mine Ayse
Erdogan, Nusret
Yalcin, A. Suha
Aktan, Ozdemir Ahmet
TI Whey Protein Versus Whey Protein Hydrolyzate for the Protection of Azoxymethane and Dextran Sodium Sulfate Induced Colonic Tumors in Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancer; Azoxymethane; Dextran sodium sulfate; Whey protein; Whey protein hydrolyzate
ID Colon cancer; Azoxymethane; Dextran sodium sulfate; Whey protein; Whey protein hydrolyzate
AB Recent studies have shown that whey protein has many useful effects including its anti-cancer effect. In this study we have compared the protective effect of dietary whey protein with whey protein hydrolyzate against azoxymethane and dextran sodium sulfate induced colon cancer in rats. We used a rat model of the colon cancer induced by administration of azoxymethane followed by repeated dextran sodium sulfate ingestion which causes multiple tumor development. Colon tissues were analyzed histologically in addition to biochemical analyses performed by measuring lipid peroxidation, protein oxidation and glutathione levels in both of colon and liver tissues of rats after sacrification. Macroscopic and microscopic tumors were identified in all groups that received azoxymethane followed by repeated dextran sodium sulfate. Group fed with whey protein hydrolyzate showed significantly less macroscopic and microscopic tumor development compared with group fed with whey protein. The protocol applied to generate an appropriate model of colon cancer was successful. Whey protein hydrolyzate was found to be more effective in preventing colon tumor development compared with whey protein.
C1 [Attaallah, Wafi] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
[Yilmaz, Mine Ayse] Marmara University, School of Medicine, Department of BiochemistryIstanbul, Turkey.
[Erdogan, Nusret] Taksim Education and Research Hospital, Department of PathologyIstanbul, Turkey.
[Yalcin, A. Suha] Marmara University, School of Medicine, Department of BiochemistryIstanbul, Turkey.
[Aktan, Ozdemir Ahmet] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
RP Attaallah, W (reprint author), Marmara University, School of Medicine, Department of General Surgery, Istanbul, Turkey.
EM drwafi2003@yahoo.com
CR Bissahoyo A, Pearsall RS, Hanlon K, Vicky A, Donna H, Virginia LG, David WT, 2005, Azoxymethane is a genetic backgrounddependent colorectal tumor initiator and promoter in mice: effects of dose, route, and diet. Toxicol Sci 88:340–345
Hakkak R, Korourian S, Ronis MJJ, Johnston JM, Badger TM, 2001, Dietary whey protein protect against azoxymethane-induced colon tumors in male rats. Cancer Epidem Biomar 10:555–558
Xiao R, Badger TM, Simmen FA, 2005, Dietary exposure to soy or whey proteins alters colonic golbal gene expression profiles during rat colon tumorigenesis. Mol Cancer 4:1
Belobrajdic DP, McIntosh GH, Owens JA, 2003, Whey proteins protect more than red meat against azoxymethane induced ACF in Wistar rats. Cancer Lett 198:43–51
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 817
EP 822
DI 10.1007/s12253-012-9509-9
PG 6
ER
PT J
AU Rubovszky, G
Horvath, Zs
Toth, E
Lang, I
Kasler, M
AF Rubovszky, Gabor
Horvath, Zsolt
Toth, Erika
Lang, Istvan
Kasler, Miklos
TI Significance of Histomorphology of Early Triple-Negative Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Triple-negative breast cancer; Vascular invasion; Necrosis; Irradiation
ID Triple-negative breast cancer; Vascular invasion; Necrosis; Irradiation
AB Triple-negative breast cancer (TNBC) is a heterogeneous disease. Possibly genetic characterisation provides the most appropriate information on tumour biology and prognosis, but it is only limitedly available in clinical practice. The aim of this investigation was to explore what additional prognostic information could be gained from detailed histomorphologic report. Patients and method: patients were selected retrospectively operated from 2005 to 2009 in one institution and charts were revised. Beyond age, tumour and nodal status, histologic grade and therapy, the additional pathologic characteristics were also involved in analysis: necrosis, lymphocytic infiltration, peritumoural vascular invasion (PVI), perineural invasion, DCIS extent and grade, perinodal spread, mitotic activity index (MAI). Results: 295 early TNBC were involved. In univariate survival analysis with a mean follow-up of 3.57 years the tumour size, the nodal status, type of operation (conservation or mastectomy), irradiation, PVI and perinodal spread proved to be significantly connected with both disease free survival (DFS) and breast cancer specific overall survival (BSOS), and necrosis and chemotherapy with BSOS. Necrosis analysed together with lymphocytic infiltrate showed greater predicting power. In multivariate analysis nodal metastasis, necrosis positive/lymphacytic infiltration negative status and lack of irradiation has significant negative impact on DFS (p0<0.0001 HR:1.98 [1.4–2.77], p0<0.017 HR:2.1 [1.1–3.8], p0<0.001 HR:0.25 [0.11–0.57], respectively) and BSOS (p0<0.0001 HR:2.47 [1.8–3.4], p0<0.017 HR:3.7 [1.6–8.2], p0<0.0017 HR:0.24 [0.1–0.58], respectively). For DFS perivascular invasion also showed significant effect (p0<0.042 HR:2.5 [1.0–6.0]). Nodal status was the strongest prognostic parameter but other histomorphologic parameters can be used for prognosis prediction.
C1 [Rubovszky, Gabor] National Institute of OncologyBudapest, Hungary.
[Horvath, Zsolt] National Institute of OncologyBudapest, Hungary.
[Toth, Erika] National Institute of OncologyBudapest, Hungary.
[Lang, Istvan] National Institute of OncologyBudapest, Hungary.
[Kasler, Miklos] National Institute of OncologyBudapest, Hungary.
RP Rubovszky, G (reprint author), National Institute of Oncology, Budapest, Hungary.
EM garub@oncol.hu
CR Rakha EA, El-Sayed ME, Green AR et al, 2007, Prognostic markers in triple-negative breast cancer. Cancer 109:25–32
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 823
EP 831
DI 10.1007/s12253-012-9510-3
PG 9
ER
PT J
AU Yuan, J
Tu, Y
Mao, X
He, Sh
Wang, L
Fu, G
Zong, J
Zhang, Y
AF Yuan, Jun
Tu, Yanyang
Mao, Xinggang
He, Shiming
Wang, Liang
Fu, Guoqiang
Zong, Jianhai
Zhang, Yongsheng
TI Increased Expression of FAT10 is Correlated with Progression and Prognosis of Human Glioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; FAT10; Immunochemistry assay; Quantitative real-time PCR; Western blot analysis; Prognosis
ID Glioma; FAT10; Immunochemistry assay; Quantitative real-time PCR; Western blot analysis; Prognosis
AB FAT10, as a small ubiquitin-like modifier, plays an important role in various cellular processes, including mitosis, immune response, and apoptosis, the dys-regulation of which may arise tumorigenesis. Therefore, the aim of this study was to examine the expression of FAT10 at gene and protein levels in glioma samples with different WHO grades and its association with survival. One hundred and twentyeight glioma specimens and 10 non-neoplastic brain tissues were collected. Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of FAT10. Kaplan-Meier method and Cox’s proportional hazards model were used in survival analysis. Immunohistochemistry showed that FAT10 protein was over-expressed in glioma tissues. FAT10 mRNA and protein levels were both higher in glioma compared to control on real-time PCR and Western blot analysis (both P<0.001). Additionally, its expression levels increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry analysis and Western blot. Moreover, the survival rate of FAT10-positive patients was significantly lower than that of FAT10-negative patients (P<0.001). We further confirmed that the increased expression of FAT10 was a significant and independent prognostic indicator in glioma by multivariate analysis (P<0.001). Our data provides convincing evidence for the first time that the increased expression of FAT10 at gene and protein levels is correlated with poor outcome in patients with glioma. FAT10 may promote the aggressiveness of glioma and may be a potential prognosis predictor of glioma.
C1 [Yuan, Jun] Fourth Military Medical University, Tangdu Hospital, Administrative Department, 710038 Xi’an, China.
[Tu, Yanyang] Fourth Military Medical University, Tangdu Hospital, Department of Emergency, 710038 Xi’an, China.
[Mao, Xinggang] 254th Hospital of PLA, Department of Neurosurgery, 300142 Tianjin, China.
[He, Shiming] Fourth Military Medical University, Tangdu Hospital, Department of Neurosurgery, 710038 Xi’an, China.
[Wang, Liang] Fourth Military Medical University, Tangdu Hospital, Department of Neurosurgery, 710038 Xi’an, China.
[Fu, Guoqiang] Fourth Military Medical University, Tangdu Hospital, Department of Emergency, 710038 Xi’an, China.
[Zong, Jianhai] Fourth Military Medical University, Tangdu Hospital, Department of Neurosurgery, 710038 Xi’an, China.
[Zhang, Yongsheng] Fourth Military Medical University, Tangdu Hospital, Administrative Department, 710038 Xi’an, China.
RP Zhang, Y (reprint author), Fourth Military Medical University, Tangdu Hospital, Administrative Department, 710038 Xi’an, China.
EM zhangys@fmmu.edu.cn
CR Ohgaki H, Kleihues P, 2005, Epidemiology and etiology of gliomas. Acta Neuropathol 109:93
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 833
EP 839
DI 10.1007/s12253-012-9511-2
PG 7
ER
PT J
AU Hewala, IT
Abd El-Monaim, AN
Anwar, M
Ebied, AS
AF Hewala, I Taha
Abd El-Monaim, A Nadia
Anwar, Medhat
Ebied, A Samia
TI The Clinical Significance of Serum Soluble Fas and p53 Protein in Breast Cancer Patients: Comparison with Serum CA 15-3
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Apoptosis; Soluble Fas; p53 protein; CA 15-3; Diagnosis; Surgery; FAC chemotherapy
ID Breast cancer; Apoptosis; Soluble Fas; p53 protein; CA 15-3; Diagnosis; Surgery; FAC chemotherapy
AB Serum sFas and p53 protein have been observed in breast cancer patients, but their clinical usefulness for diagnosis and therapy monitoring has not been clarified. The aim of this study was to compare the clinical utility of serumsFas and p53 protein with that of serumCA 15-3 as the most commonly used breast cancer tumor marker. Serum samples were taken from 35 normal healthy controls and 35 breast cancer patients before surgery, after 2 weeks of surgery and after six cycles of FAC chemotherapy. Serum sFas and p53 protein levels were measured using ELISA kits. Serum CA 15-3 levels were determined using IRMA kit. Mean Serum levels of sFas and CA 15-3 were significantly elevated while p53 protein was significantly declined in breast caner patients than controls. Serum p53 protein showed the greatest significant area under the ROC curve (84.3%) followed by sFas (80.5%), then CA 15-3 (78%). The sensitivity, specificity and cut-off value for diagnosing breast cancer patients were 84.2%, 82.6% and 2.88 U/ml for p53 protein, 83.3%, 68.2% and 497.3 pg/ml for sFas and 45.8%, 100% and 23 U/ml for CA15-3. Surgical removal of breast resulted in a significant decline in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. Six cycles of chemotherapy resulted in a significant elevation in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. sFas was significantly correlated with tumor grade. It could be concluded that although serum p53 protein is superior to sFas and CA15-3 for diagnosis of breast cancer patients, only sFas is useful for monitoring the response of breast cancer patients to surgery and chemotherapy if the effect of systemic inflammatory reactions is excluded.
C1 [Hewala, I Taha] Alexandria University, Medical Research Institute, Department of Radiation Sciences, 165 El-Horria Avenue, El Hadara, 21561 Alexandria, Egypt.
[Abd El-Monaim, A Nadia] Alexandria University, Medical Research Institute, Department of Cancer Management and Research, 165 El-Horria Avenue, El Hadara, 21561 Alexandria, Egypt.
[Anwar, Medhat] Alexandria University, Medical Research Institute, Department of Experimental and Clinical Surgery, 165 El-Horria Avenue, El Hadara, 21561 Alexandria, Egypt.
[Ebied, A Samia] Alexandria University, Medical Research Institute, Department of Applied Medical Chemistry, 165 El-Horria Avenue, El Hadara, 21561 Alexandria, Egypt.
RP Hewala, IT (reprint author), Alexandria University, Medical Research Institute, Department of Radiation Sciences, 21561 Alexandria, Egypt.
EM tahahewala@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 841
EP 848
DI 10.1007/s12253-012-9512-1
PG 8
ER
PT J
AU Zamirska, A
Matusiak,
Dziegiel, P
Szybejko-Machaj, G
Szepietowski, CJ
AF Zamirska, Aleksandra
Matusiak, Lukasz
Dziegiel, Piotr
Szybejko-Machaj, Grazyna
Szepietowski, C Jacek
TI Expression of Metallothioneins in Cutaneous Squamous Cell Carcinoma and Actinic Keratosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metallothioneins; Squamous cell carcinoma; Actinic keratosis; Ki-67; Skin
ID Metallothioneins; Squamous cell carcinoma; Actinic keratosis; Ki-67; Skin
AB Metallothioneins (MT) are low-molecular weight proteins implicated in heavy metal detoxification, zinc and cooper homeostasis and cell protection against free radicals. In variety of cancers MT-overexpression was shown, but there are just a few studies on the role of MT in skin carcinogenesis. Current study was undertaken to evaluate MT and Ki-67 expression in pre-cancerous skin lesions as well as in fully developed skin cancers. 73 squamous cell carcinomas (SCC), 23 actinic keratoses (AK) and 20 normal skin samples were included in the study. In obtained paraffin sections immunohistochemical reactions were performed. MT-expression in SCC (mean 2.89±1.83) was significantly higher than in AK (mean 1.69±1.26)(p00.006) and higher than in normal skin (mean 2±0.79) (p00.0075). The MT-expression positively correlated with Ki-67 expression (R00.28; p00.017) in SCC and in AK (R00.49; p00.018). Various clinico-pathological variables, e.g. morphology, size of lesions and the depth of neoplastic infiltration were not associated to MT-expression in both SCC and AK. The grade of histological differentiation of SCC correlated positively with Ki-67 antigen (p<0.001) and did not correlate with MT-expression (p00.06). Ki-67 expression was higher in SCC and in AK than in healthy skin (p00,003). In SCC and in AK expression of Ki-67 antigen correlated positively with MT-expression (respectively p00.017 and p00.018). MT may serve as a good markers of proliferation in SCC and AK. MT-overexpression in SCC may suggest a potential role of MT in skin carcinogenesis.
C1 [Zamirska, Aleksandra] Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Chalubinskiego 1, 50-368 Wroclaw, Poland.
[Matusiak, Lukasz] Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Chalubinskiego 1, 50-368 Wroclaw, Poland.
[Dziegiel, Piotr] Wroclaw Medical University, Department of Human Morphology and EmbryologyWroclaw, Poland.
[Szybejko-Machaj, Grazyna] Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Chalubinskiego 1, 50-368 Wroclaw, Poland.
[Szepietowski, C Jacek] Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Chalubinskiego 1, 50-368 Wroclaw, Poland.
RP Matusiak, (reprint author), Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, 50-368 Wroclaw, Poland.
EM luke71@interia.pl
CR Dziegiel P, 2004, Expression of metallothioneins in tumor cells. Pol J Pathol 55:3–12
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Palmiter RD, Findley SD, Whitmore TE et al, 1992, MT-III, a brain-specific member of the metallothionein gene family. Proc Natl Acad Sci USA 89:6333–7
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 849
EP 855
DI 10.1007/s12253-012-9513-0
PG 7
ER
PT J
AU Kenessey, I
Banki, B
Mark,
Varga, N
Tovari, J
Ladanyi, A
Raso, E
Timar, J
AF Kenessey, Istvan
Banki, Balazs
Mark, Agnes
Varga, Norbert
Tovari, Jozsef
Ladanyi, Andrea
Raso, Erzsebet
Timar, Jozsef
TI Revisiting CB1 Receptor as Drug Target in Human Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CB1 receptor; Endocannabinoid; Human malignant melanoma; Metastasis
ID CB1 receptor; Endocannabinoid; Human malignant melanoma; Metastasis
AB Previous studies have indicated the antitumoral effect of human melanocytes, human melanoma cell lines expressing CB1 receptor (CB1), and of the peritumoral administration of endocannabinoids. In the present study, we systematically screened several human melanoma cell lines for the expression of CNR1 and demonstrated transcription of the authentic gene. The product of CNR1, the CB1 protein, was found localized to the cell membrane as well as to the cytoskeleton. Further, the studied human melanoma cell lines expressed functional CB1 since physiological and synthetic ligands, anandamide (AEA), Met- F-AEA, ACEA and AM251 showed a wide range of biological effects in vitro, for example anti-proliferative, proapoptotic and anti-migratory. More importantly, our studies revealed that systemic administration of a stable CB1 agonist, ACEA, into SCID mice specifically inhibited liver colonization of human melanoma cells. Since therapeutic options for melanoma patients are still very limited, the endocannabinoid-CB1 receptor system may offer a novel target.
C1 [Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Banki, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Mark, Agnes] National Institute of OncologyBudapest, Hungary.
[Varga, Norbert] National Institute of OncologyBudapest, Hungary.
[Tovari, Jozsef] National Institute of OncologyBudapest, Hungary.
[Ladanyi, Andrea] National Institute of OncologyBudapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Kenessey, I (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM steveken12@yahoo.com
CR Wang J, Ueda N, 2009, Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat 89:112–119
Flygare J, Sander B, 2008, The endocannabinoid system in cancerpotential therapeutic target? Semin Cancer Biol 18:176–189
Mouslech Z, Valla V, 2009, Endocannabinoid system: an overview of its potential in current medical practice. Neuro Endocrinol Lett 30:153–179
Bifulco M, Di Marzo V, 2002, Targeting the endocannabinoid system in cancer therapy: a call for further research. Nat Med 8:547–550
Alexander A, Smith PF, Rosengren RJ, 2009, Cannabinoids in the treatment of cancer. Cancer Lett 285:6–12
Alpini G, Demorrow S, 2009, Changes in the endocannabinoid system may give insight into new and effective treatments for cancer. Vitam Horm 81:469–485
Fowler CJ, Gustafsson SB, Chung SC et al, 2010, Targeting the endocannabinoid system for the treatment of cancer–a practical view. Curr Top Med Chem 10:814–827
Bifulco M, Malfitano AM, Pisanti S et al, 2008, Endocannabinoids in endocrine and related tumours. Endocr Relat Cancer 15:391–408
Portella G, Laezza C, Laccetti P et al, 2003, Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis. FASEB J 17:1771–1773
Pisanti S, Bifulco M, 2009, Endocannabinoid system modulation in cancer biology and therapy. Pharmacol Res 60:107–116
Bifulco M, Laezza C, Gazzerro P et al, 2007, Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion, review). Oncol Rep 17:813–816
Sarfaraz S, Afaq F, Adhami VM et al, 2005, Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res 65:1635–1641
Gazzerro P, Malfitano AM, Proto MC et al, 2010, Synergistic inhibition of human colon cancer cell growth by the cannabinoid CB1 receptor antagonist rimonabant and oxaliplatin. Oncol Rep 23:171–175
Biro T, Toth BI, Hasko G et al, 2009, The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci 30:411–420
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Blazquez C, Carracedo A, Barrado L et al, 2006, Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J 20:2633–2635
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Sarnataro D, Grimaldi C, Pisanti S et al, 2005, Plasma membrane and lysosomal localization of CB1 cannabinoid receptor are dependent on lipid rafts and regulated by anandamide in human breast cancer cells. FEBS Lett 579:6343–6349
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European public assessment report. Acomplia. http://www.ema.europa. eu/docs/en_GB/document_library/EPAR_-_Summary_for_ the_public/human/000666/WC500021282.pdf.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 857
EP 866
DI 10.1007/s12253-012-9515-y
PG 10
ER
PT J
AU Jethon, A
Pula, B
Piotrowska, A
Wojnar, A
Rys, J
Dziegiel, P
Podhorska-Okolow, M
AF Jethon, Aleksandra
Pula, Bartosz
Piotrowska, Aleksandra
Wojnar, Andrzej
Rys, Janusz
Dziegiel, Piotr
Podhorska-Okolow, Marzena
TI Angiotensin II Type 1 Receptor (AT-1R) Expression Correlates with VEGF-A and VEGF-D Expression in Invasive Ductal Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiotensin receptors; VEGF; Angiogenesis; Lymphangiogenesis; Breast cancer
ID Angiotensin receptors; VEGF; Angiogenesis; Lymphangiogenesis; Breast cancer
AB Recent studies point to the involvement of angiotensin II (Ang II) receptor type 1 (AT-1R) on processes of metastasing, stimulation of invasiveness and angiogenesis in tumours. In this study, the correlation between intensity of AT-1R expression and expression of lymph- and angiogenesis markers in invasive ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced AT- 1R expression. Expression intensity of AT-1R was found to correlate with expressions of VEGF-A (r00.26; p00.008) and VEGF-D (r00.24; p00.015). Out of the examined markers of angiogenesis and lymphangiogenesis only the pronounced expression of VEGF-C was found to correlate with patient poor clinical outcome (p00.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could point to stimulatory action of Ang II on their expression what might result in augmented lymph- and angiogenesis in IDC.
C1 [Jethon, Aleksandra] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Pula, Bartosz] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Piotrowska, Aleksandra] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Wojnar, Andrzej] Lower Silesian Centre of Oncology, Department of PathomorphologyWroclaw, Poland.
[Rys, Janusz] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of Tumour PathologyKrakow, Poland.
[Dziegiel, Piotr] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Podhorska-Okolow, Marzena] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
RP Podhorska-Okolow, M (reprint author), Wroclaw Medical University, Department of Human Morphology and Embryology, 50-368 Wroclaw, Poland.
EM marzenna.podhorska-okolow@am.wroc.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 867
EP 873
DI 10.1007/s12253-012-9516-x
PG 7
ER
PT J
AU Giaginis, C
Politi, E
Alexandrou, P
Sfiniadakis, J
Kouraklis, G
Theocharis, S
AF Giaginis, Costantinos
Politi, Ekaterini
Alexandrou, Paraskevi
Sfiniadakis, John
Kouraklis, Gregory
Theocharis, Stamatios
TI Expression of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) in Human Non-small Cell Lung Carcinoma: Correlation with Clinicopathological Parameters, Proliferation and Apoptosis Related Molecules and Patients’ Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PPAR-γ; Non-small cell lung carcinoma; Immunohistochemistry; Cell cycle; Cell proliferation; Apoptosis
ID PPAR-γ; Non-small cell lung carcinoma; Immunohistochemistry; Cell cycle; Cell proliferation; Apoptosis
AB Peroxisome proliferator-activated receptor-γ (PPAR-γ) has currently been considered as molecular target for the treatment of human metabolic disorders. PPAR-γ has also been implicated in the pathogenesis and progression of several types of cancer, being associated with cell differentiation, growth and apoptosis. The present study aimed to evaluate the clinical significance of PPAR-γ expression in non-small cell lung carcinoma (NSCLC). PPAR-γ protein expression was assessed immunohistochemically in tumoral samples of 67 NSCLC patients and was statistically analyzed in relation to clinicopathological parameters, proliferation and apoptosis related molecules and patients’ survival. Positive PPAR-γ expression was prominent in 30 (45 %) out of 67 NSCLC cases. PPAR-γ positivity was more frequently observed in squamous cell lung carcinoma cases compared to lung adenocarcinoma ones (p00.048). PPAR-γ positivity was significantly associated with bcl-2 positivity (p00.016) and borderline with c-myc positivity (p00.052), whereas non associations with grade of differentiation, TNM stage, Ki-67, p53, bax proteins’ expression and patients’ survival were noted. In the subgroup of squamous cell lung carcinoma cases, PPAR-γ positivity was significantly associated with tumor size (p00.038), while in lung adenocarcinoma ones with histopathological grade of differentiation (p00.026). The present study supported evidence for possible participation of PPAR-γ in the biological mechanisms underlying the carcinogenic evolution of the lung. Although the survival prediction using PPAR-γ expression as a marker seems uncertain, the observed correlation with apoptosis related proteins reinforces the potential utility of PPAR-γ ligands as cell cycle modulators in future therapeutic approaches in lung cancer.
C1 [Giaginis, Costantinos] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias Street, 11527 Athens, Greece.
[Politi, Ekaterini] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias Street, 11527 Athens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias Street, 11527 Athens, Greece.
[Sfiniadakis, John] Naval Hospital Athens, Department of Pathology, 70, Dinokratous Street, 11521 Athens, Greece.
[Kouraklis, Gregory] University of Athens, Medical School, Second Department of Propedeutic Surgery, 17, Ag. Thoma Street, 11527 Athens, Greece.
[Theocharis, Stamatios] University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 75 Mikras Asias Street, 11527 Athens, Greece.
RP Giaginis, C (reprint author), University of Athens, Medical School, Department of Forensic Medicine and Toxicology, 11527 Athens, Greece.
EM cgiaginis@yahoo.gr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 875
EP 883
DI 10.1007/s12253-012-9517-9
PG 9
ER
PT J
AU Zaczek, A
Markiewicz, A
Supernat, A
Bednarz-Knoll, N
Brandt, B
Seroczynska, B
Skokowski, J
Szade, J
Czapiewski, P
Biernat, W
Welnicka-Jaskiewicz, M
Jassem, J
AF Zaczek, Anna
Markiewicz, Aleksandra
Supernat, Anna
Bednarz-Knoll, Natalia
Brandt, Burkhardt
Seroczynska, Barbara
Skokowski, Jaroslaw
Szade, Jolanta
Czapiewski, Piotr
Biernat, Wojciech
Welnicka-Jaskiewicz, Marzena
Jassem, Jacek
TI Prognostic Value of TOP2A Gene Amplification and Chromosome 17 Polysomy in Early Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Chromosome 17 polysomy; TOP2A amplification; qPCR; FISH; Prognostic factor
ID Breast cancer; Chromosome 17 polysomy; TOP2A amplification; qPCR; FISH; Prognostic factor
AB The aim of this study was to analyze the occurrence of TOP2A gene amplification and chromosome 17 polysomy in patients with early breast cancer and to correlate the status of these alterations with the prognostic significance expressed as patients’ clinical features and survival. Such concurrent analyses of TOP2A gene status and chromosome 17 polysomy have not been performed before. Study group included 149 consecutive stage I-III patients administered standard multimodality treatment. TOP2A abnormalities were examined by standard fluorescence in situ hybridization (FISH) and developed by our group quantitative real-time PCR (qPCR). TOP2A amplification and deletion assessed by FISH were found in 23% and 7% of the tumours, respectively, and by qPCR in 31% and 11% of the tumours, respectively. Chromosome 17 polysomy was detected in 40% of the cases. TOP2A amplification (by qPCR) correlated with shorter diseasefree survival (p00.03) and overall survival (p00.047), and the prognostic value of TOP2A was confirmed in the multivariate analysis (HR03.22, 95% CI 1.09–9.56, p00.03). TOP2A gene amplification, but not chromosome 17 polysomy, carries negative prognostic information in early breast cancer. Given the aforementioned results, qPCR might serve as a prognostic tool in determining the patient’s prognosis.
C1 [Zaczek, Anna] University of Gdansk and Medical University of Gdansk, Intercollegiate Faculty of Biotechnology, Laboratory of Cell Biology, Department of Medical Biotechnology, Debinki 1, 80-211 Gdansk, Poland.
[Markiewicz, Aleksandra] University of Gdansk and Medical University of Gdansk, Intercollegiate Faculty of Biotechnology, Laboratory of Cell Biology, Department of Medical Biotechnology, Debinki 1, 80-211 Gdansk, Poland.
[Supernat, Anna] University of Gdansk and Medical University of Gdansk, Intercollegiate Faculty of Biotechnology, Laboratory of Cell Biology, Department of Medical Biotechnology, Debinki 1, 80-211 Gdansk, Poland.
[Bednarz-Knoll, Natalia] University Medical Centre, Institute of Tumour Biology, Hamburg-Eppendorf, Martinistrasse 52, 20-246 Hamburg, Germany.
[Brandt, Burkhardt] University Medical Centre, Institute of Tumour Biology, Hamburg-Eppendorf, Martinistrasse 52, 20-246 Hamburg, Germany.
[Seroczynska, Barbara] Medical University of Gdansk, Bank of Frozen Tissues and Genetic Specimen, Debinki 1, 80-211 Gdansk, Poland.
[Skokowski, Jaroslaw] Medical University of Gdansk, Bank of Frozen Tissues and Genetic Specimen, Debinki 1, 80-211 Gdansk, Poland.
[Szade, Jolanta] Medical University of Gdansk, Department of Pathomorphology, Debinki 7, 80-211 Gdansk, Poland.
[Czapiewski, Piotr] Medical University of Gdansk, Department of Pathomorphology, Debinki 7, 80-211 Gdansk, Poland.
[Biernat, Wojciech] Medical University of Gdansk, Department of Pathomorphology, Debinki 7, 80-211 Gdansk, Poland.
[Welnicka-Jaskiewicz, Marzena] Medical University of Gdansk, Department of Oncology and Radiotherapy, Debinki 7, 80-211 Gdansk, Poland.
[Jassem, Jacek] Medical University of Gdansk, Department of Oncology and Radiotherapy, Debinki 7, 80-211 Gdansk, Poland.
RP Zaczek, A (reprint author), University of Gdansk and Medical University of Gdansk, Intercollegiate Faculty of Biotechnology, Laboratory of Cell Biology, Department of Medical Biotechnology, 80-211 Gdansk, Poland.
EM azaczek@gumed.edu.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 885
EP 894
DI 10.1007/s12253-012-9518-8
PG 10
ER
PT J
AU Ding, Y
Huang, X
Liu, T
Fu, Y
Tan, Z
Zheng, H
Zhou, T
Dai, J
Xu, W
AF Ding, Yan
Huang, Xiaobing
Liu, Taiping
Fu, Yong
Tan, Zhangping
Zheng, Hong
Zhou, Taoli
Dai, Jigang
Xu, Wenyue
TI The Plasmodium Circumsporozoite Protein, a Novel NF-κB Inhibitor, Suppresses the Growth of SW480
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circumsporozoite protein; Nuclear transcription factor κB; Human colon cancer cell line; Proliferation; Apoptosis
ID Circumsporozoite protein; Nuclear transcription factor κB; Human colon cancer cell line; Proliferation; Apoptosis
AB The blocking of NF-κB activation is a promising strategy for the treatment of colorectal cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was recently reported to block NF-κB activation in hepatocytes. Thus, we investigated the effect of the CSP on the growth of the human colon cancer cell line, SW480. We demonstrated that transfection with a recombinant plasmid expressing CSP inhibited the proliferation of SW480 in a dose-dependent manner and induced the apoptosis of SW480. A NF-κB gene reporter assay showed that both the CSP and its nuclear localization signal (NLS) motif could equally suppress the activation of NF-κB following the stimulation with human recombinant TNF-α in the SW480. Furthermore, western blot analysis indicated that NLS did not affect the phosphorylation and degradation of IκB, but could sharply inhibit the nuclear translocation of NF-κB in TNF-α stimulated SW480. Hence, our data suggest that the CSP might be explored as a new NF-κB inhibitor for the treatment of colorectal cancer.
C1 [Ding, Yan] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Huang, Xiaobing] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400037 Chongqing, China.
[Liu, Taiping] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Fu, Yong] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Tan, Zhangping] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Zheng, Hong] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Zhou, Taoli] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
[Dai, Jigang] The Third Military Medical University, Xinqiao Hospital, Department of Thoracic Surgery, 400037 Chongqing, China.
[Xu, Wenyue] Third Military Medical University, Department of Pathogenic Biology, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
RP Dai, J (reprint author), The Third Military Medical University, Xinqiao Hospital, Department of Thoracic Surgery, 400037 Chongqing, China.
EM 691057831@qq.com
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PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
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J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 895
EP 902
DI 10.1007/s12253-012-9519-7
PG 8
ER
PT J
AU Wang, Y
Wang, X
Yang, Z
Zhu, G
Chen, D
Meng, Z
AF Wang, Yongzhi
Wang, Xinghuan
Yang, Zhonghua
Zhu, Guangbin
Chen, Dong
Meng, Zhe
TI Menthol Inhibits the Proliferation and Motility of Prostate Cancer DU145 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Menthol; Migration; Proliferation; Prostate cancer; Transient receptor potential (TRP) channel
ID Menthol; Migration; Proliferation; Prostate cancer; Transient receptor potential (TRP) channel
AB In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgenindependent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p<0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G0/G1 phase (p<0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent.
C1 [Wang, Yongzhi] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Wang, Xinghuan] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Yang, Zhonghua] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Zhu, Guangbin] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Chen, Dong] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Meng, Zhe] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
RP Wang, X (reprint author), Wuhan University, Zhongnan Hospital, Department of Urology, 430071 Wuhan, China.
EM urologistwxh@gmail.com
CR Jemal A, Siegel R, Ward E et al, 2007, Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66
Chen Y, Clegg NJ, Scher HI, 2009, Anti-androgens and androgendepleting therapies in prostate cancer: new agents for an established target. Lancet Oncol 10(10):981–991
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Taplin ME, 2007, Drug insight: role of the androgen receptor in the development and progression of prostate cancer. Nat Clin Pract Oncol 4(4):236–244
Damber JE, Aus G, 2008, Prostate cancer. Lancet 371(9625):1710– 1721
Legrand G, Humez S, Slomianny C et al, 2001, Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control. J Biol Chem 276(50):47608–47614
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Vanoverberghe K, Vanden Abeele F, Mariot P et al, 2004, Ca2+ homeostasis and apoptotic resistance of neuroendocrinedifferentiated prostate cancer cells. Cell Death Differ 11(3):321–330
Skryma R, Mariot P, Bourhis XL et al, 2000, Store depletion and store-operated Ca2+ current in human prostate cancer LNCaP cells: involvement in apoptosis. J Physiol 527(Pt 1):71–83
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Vanden Abeele F, Roudbaraki M, Shuba Y, Skryma R, Prevarskaya N, 2003, Store-operated Ca2+ current in prostate cancer epithelial cells. Role of endogenous Ca2+ transporter type 1. J Biol Chem 278(17):15381–15389
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Tsavaler L, Shapero MH, Morkowski S, Laus R, 2001, Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61(9):3760– 3769
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Zhang L, 2004, Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64(22):8365–8373
Valero M, Morenilla-Palao C, Belmonte C, Viana F, 2010, Pharmacological and functional properties of TRPM8 channels in prostate tumor cells. Pflugers Arch-Eur J Physiol 461(1):99– 114
Kim S, Nam J, Park E, Kim B, So I, Jeon J, 2009, Menthol regulates TRPM8-independent processes in PC-3 prostate cancer cells. BBA-Mol Basis Dis 1792(1):33–38
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 903
EP 910
DI 10.1007/s12253-012-9520-1
PG 8
ER
PT J
AU Zhang, Y
Deng, Zsh
Liao, Mm
Wang, N
Zhang, Xq
Yu, Hy
Zhang, Yd
AF Zhang, Yang
Deng, Zhan-sheng
Liao, Ming-mei
Wang, Ning
Zhang, Xiao-qing
Yu, Hai-yang
Zhang, Yang-de
TI Tumor Associated Glycoprotein-72 is a Novel Marker for Poor Survival in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Tumor associated glycoprotein-72; Clinicopathology; Prognosis; Disease-free survival; Overall survival
ID Hepatocellular carcinoma; Tumor associated glycoprotein-72; Clinicopathology; Prognosis; Disease-free survival; Overall survival
AB To investigate the relationship of tumor associated glycoprotein-72 (TAG-72) expression with clinicopathological features in hepatocellular carcinoma (HCC) patients. Sixty pairs of HCC and paracarcinomatous (PCLT) tissues, and 10 nomral liver (NL) tissues were collected for Western blot analysis, and 244 pairs of HCC and PCLT tissues were collected for immunohistochemistry analysis. TAG-72 protein expression was elevated significantly in HCC tissues compared with PCLT and NL tissues. Its increased expression was correlated with TNM stage, Edmondson-Steiner grade, vein invasion and multiple tumor nodes. It is noteworthy that the HCC patients with high TAG-72 expression had shorter overall survival and disease-free survival than the patients with low expression. Multivariate Cox regression analysis revealed that TAG-72 expression was an independent prognostic factor for HCC patients. The current study demonstrated for the first time that the increased expression of TAG-72 was correlated with poor survival in patients with HCC, indicating that TAG-72 is a novel prognostic marker for HCC.
C1 [Zhang, Yang] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Deng, Zhan-sheng] Central South University, The First Xiangya Hospital, Department of Orthopedics, 410008 Changsha, Hunan Province, China.
[Liao, Ming-mei] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Wang, Ning] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Zhang, Xiao-qing] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Yu, Hai-yang] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
[Zhang, Yang-de] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, Hunan Province, China.
RP Zhang, Yd (reprint author), Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, 410008 Changsha, China.
EM zhangyd99@sina.cn
CR Zhang MF, Zhang ZY, Fu J, Yang YF, Yun JP, 2009, Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma. J Transl Med 7:110
Teo EK, Fock KM, 2001, Hepatocellular carcinoma: an Asian perspective. Dig Dis 19:263–268
Leoni S, Piscaglia F, Righini R, Bolondi L, 2006, Management of small hepatocellular carcinoma. Acta Gastroenterol Belg 69:230– 235
Jin B, Wang X, Jin Y et al, 2009, Detection of serum gastric cancer-associated MG7-Ag from gastric cancer patients using a sensitive and convenient ELISA method. Cancer Invest 27:227– 233
Molina R, Auge JM, Escudero JM et al, 2008, Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21–1, CEA, SCC and NSE. Tumour Biol 29:371–380
Chen L, Wang Y, Liu X et al, 2008, A new TAG-72 cancer marker peptide identified by phage display. Cancer Lett 272:122–132
Kim SJ, Hong HJ, 2007, Guided selection of human antibody light chains against TAG-72 using a phage display chain shuffling approach. J Microbiol 45:572–577
Chauhan SC, Vinayek N, Maher DM et al, 2007, Combined staining of TAG-72, MUC1, and CA125 improves labeling sensitivity in ovarian cancer: antigens for multi-targeted antibodyguided therapy. J Histochem Cytochem 55:867–875
Mohsin H, Jia F, Sivaguru G, Hudson MJ et al, 2006, Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu. Bioconjug Chem 17:485– 492
Santos-Juanes J, Bernaldo de Quiros JF, Galache Osuna C et al, 2004, Apocrine carcinoma, adenopathies, and raised TAG-72 serum tumor marker. Dermatol Surg 30:566–569
Milenic DE, Brady ED, Garmestani K, Albert PS, Abdulla A, Brechbiel MW, 2010, Improved efficacy of alpha-particletargeted radiation therapy: dual targeting of human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72. Cancer 116:1059–1066
Zou P, Xu S, Povoski SP et al, 2009, Near-infrared fluorescence labeled anti-TAG-72 monoclonal antibodies for tumor imaging in colorectal cancer xenograft mice. Mol Pharm 6:428–440
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Ponnusamy MP, Venkatraman G, Singh AP et al, 2007, Expression of TAG-72 in ovarian cancer and its correlation with tumor stage and patient prognosis. Cancer Lett 251:247–257
Ouyang M, Wu W, Zou Y, Zhou J, Wang Z, Wan X, 2010, Immunoreactivity and prognostic value of tumor-associated glycoprotein 72 in primary gallbladder carcinoma. Surg Oncol 19:82– 87
Graves SS, Dearstyne E, Lin Y et al, 2003, Combination therapy with Pretarget CC49 radioimmunotherapy and gemcitabine prolongs tumor doubling time in a murine xenograft model of colon cancer more effectively than either monotherapy. Clin Cancer Res 9:3712–3721
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 911
EP 916
DI 10.1007/s12253-012-9521-0
PG 6
ER
PT J
AU Rekhi, B
Sharique, A
Basak, R
Qureshi, SS
Desai, SS
Ramadwar, M
Desai, BS
Kurkure, P
Jambhekar, AN
AF Rekhi, Bharat
Sharique, Ahmed
Basak, Ranjan
Qureshi, S Sajid
Desai, S Saral
Ramadwar, Mukta
Desai, B Sangeeta
Kurkure, Purna
Jambhekar, A Nirmala
TI Desmoplastic Small Round Cell Tumor-Clinicopathological Spectrum, Including Unusual Features and Immunohistochemical Analysis of 45 Tumors Diagnosed at a Tertiary Cancer Referral Centre, with Molecular Results t(11; 22) (p13; q12) (EWS-WT1) in Select Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Desmoplastic small round cell tumor; WT1; Roundcell tumors; Molecular analysis of synovialsarcomas; Immunohistochemistry of synovial sarcoma
ID Desmoplastic small round cell tumor; WT1; Roundcell tumors; Molecular analysis of synovialsarcomas; Immunohistochemistry of synovial sarcoma
C1 [Rekhi, Bharat] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Sharique, Ahmed] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Basak, Ranjan] Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Division of Molecular PathologyNavi Mumbai, Khargar, India.
[Qureshi, S Sajid] Tata Memorial Hospital, Pediatric Surgical Oncology Services, Parel, 400012 Mumbai, Maharashtra, India.
[Desai, S Saral] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Ramadwar, Mukta] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Desai, B Sangeeta] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
[Kurkure, Purna] Tata Memorial Hospital, Department of Medical Oncology, Parel, 400012 Mumbai, Maharashtra, India.
[Jambhekar, A Nirmala] Tata Memorial Hospital, Department of Pathology, Dr E.B. Road, Parel, 400012 Mumbai, Maharashtra, India.
RP Rekhi, B (reprint author), Tata Memorial Hospital, Department of Pathology, 400012 Mumbai, India.
EM rekhi.bharat@gmail.com
CR Antonescu CR, Gerald W, 2002, Desmoplastic small round cell tumor. In: Fletcher CDM, Unni K, Mertens F, eds, Tumors of soft tissue and bone. Pathology and genetics. World Health Organization classification of tumors. IARC, Lyon, pp 216–219
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Ordonez NG, el-Naggar AK, Ro JY, Silva EG, Mackay B, 1993, Intra-abdominal desmoplastic small cell tumor: a light microscopic, immunocytochemical, ultrastructural, and flow cytometric study. Hum Pathol 24:850–865
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Rekhi B, Basak R, Desai S, Jambhekar NA, 2010, A t, 11; 22,, p13; q12, EWS-WT-1 positive desmoplastic small round cell tumor, DSRCT, of the maxilla- An unusual case indicating role of molecular diagnosis in round cell sarcomas. J Post Grad Med 56:206–210
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 917
EP 927
DI 10.1007/s12253-012-9522-z
PG 11
ER
PT J
AU Hassumi-Fukasawa, KM
Miranda-Camargo, AF
Zanetti, RB
Galano, FD
Ribeiro-Silva, A
Soares, GE
AF Hassumi-Fukasawa, Kazue Marcela
Miranda-Camargo, Alves Fabiana
Zanetti, Riedo Bruna
Galano, Faria Denise
Ribeiro-Silva, Alfredo
Soares, Garcia Edson
TI Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BAG-1; PARP-1; HPV; Cervix; PCR; Immunohistochemistry
ID BAG-1; PARP-1; HPV; Cervix; PCR; Immunohistochemistry
AB Cervical cancer remains persistently the second most common malignancies among women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the estimate is for 18,430 new cases in 2011. Several types of molecular markers have been studied in carcinogenesis including proteins associated with apoptosis such as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and invasive squamous cell carcinomas (SCCs) of the uterine cervix and to verify a possible association with HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG-1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1 expression levels were significantly different between LSILs and HSILs (p00,014) and between LSILs and SCCs (p00,014). In regards to PARP-1 expression, we found significant differences between the expression levels in HSILs and SCCs (p00,022). No association was found between BAG-1 expression and the presence of HPV. However, a significant association was found between PARP-1 expression and HPV positivity in the HSILs group (p00,021). In conclusion our research suggests that BAG-1 expression could contribute to the differentiation between LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between HSIL HPV-related and SCC. Further studies are needed to clarify the molecular aspects of the relationship between PARP-1 expression and HPV infection, with potential applications for cervical cancer prediction.
C1 [Hassumi-Fukasawa, Kazue Marcela] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Miranda-Camargo, Alves Fabiana] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Zanetti, Riedo Bruna] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Galano, Faria Denise] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Ribeiro-Silva, Alfredo] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Soares, Garcia Edson] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, Avenida dos Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
RP Hassumi-Fukasawa, KM (reprint author), University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, 14049-900 Ribeirao Preto, Brazil.
EM marcelahassumi@usp.br
CR Nour NM, 2009, Cervical cancer: a preventable death. Rev Obstet Gynecol 4:240–244
Jayshree RS, Sreenivas A, Tessy M, Krishna S, 2009, Cell intrinsic & extrinsic factors in cervical carcinogenesis. Indian J Med Res 130:286–295
Townsend PA, Cutress RI, Carroll CJ, Lawrence KM, Scarabelli TM, Packham G, Stephanou A, Latchman DS, 2004, BAG-1 proteins protect cardiac myocytes from simulated ischemia/reperfusion- induced apoptosis via an alternate mechanism of cell survival independent of the proteasome. J Biol Chem 20:20723– 20728
Sharp A, Crabb SJ, Townsend PA, Cutress RI, Brimmell M, Wang X, Packham G, 2004, BAG-1 in carcinogenesis. Expert Rev Mol Med 6(7):1–15
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 929
EP 937
DI 10.1007/s12253-012-9523-y
PG 9
ER
PT J
AU Wu, D
Li, H
Du, W
Ji, X
Liu, W
Huang, Sh
Xiao, Y
AF Wu, Dan
Li, Huiyu
Du, Wen
Ji, Xiaoxia
Liu, Wei
Huang, Shiang
Xiao, Yi
TI Mathematical Modeling of Therapeutic Strategies for Myeloid Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hematopoietic stem cells; Cancer stem cell; Mathematical modeling; Chemotherapy
ID Hematopoietic stem cells; Cancer stem cell; Mathematical modeling; Chemotherapy
AB The existence of malignant stem cells has been proven for hematopoietic disorder as well as some solid tumors. Although significant improvements in cancer therapy have been made, tumor recurrence is frequent and can partly be due to the absence of therapeutic target which tumor stem cells are regarded as. In this paper we shall explore different therapeutic scenarios for successful tumor treatment by using a predictive mathematical model based on the cell compartment method. In particular, we shall study the effects of the chemotherapeutic target rate and of the interval of G-CSF administration on therapy for myeloid malignancies through simulating chemotherapy with G-CSF (granulocyte colony-stimulating factor) support. The results indicate that if target rate is raised to an enough high value, the efficiency of chemotherapy increases so greatly that the tumor mature cells perish completely and normal mature cells are maintained at a normal level. Furthermore, the administration of G-CSF can increase the amount of the normal mature cells to a normal level. However, too long interval of G-CSF administration is demonstrated not propitious to patients’ healing. These results indicate that the simulations may be an effective approach to help designing therapeutic scenarios for successful tumor treatment by chemotherapy.
C1 [Wu, Dan] Huazhong University of Science and Technology, Department of PhysicsWuhan, China.
[Li, Huiyu] Huazhong University of Science and Technology, Tongji Medical College, Center of Stem cellWuhan, China.
[Du, Wen] Huazhong University of Science and Technology, Tongji Medical College, Center of Stem cellWuhan, China.
[Ji, Xiaoxia] Huazhong University of Science and Technology, Department of PhysicsWuhan, China.
[Liu, Wei] Huazhong University of Science and Technology, Tongji Medical College, Center of Stem cellWuhan, China.
[Huang, Shiang] Huazhong University of Science and Technology, Tongji Medical College, Center of Stem cellWuhan, China.
[Xiao, Yi] Huazhong University of Science and Technology, Department of PhysicsWuhan, China.
RP Xiao, Y (reprint author), Huazhong University of Science and Technology, Department of Physics, Wuhan, China.
EM yxiao@mail.hust.edu.cn
CR Reya T, Morrison SJ, Clarke MF, Weissman IL, 2001, Stem cells, cancer, and cancer stem cells. Nature 414:105–111
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 939
EP 947
DI 10.1007/s12253-012-9524-x
PG 9
ER
PT J
AU Biesaga, B
Niemiec, J
Ziobro, M
AF Biesaga, Beata
Niemiec, Joanna
Ziobro, Marek
TI Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Early breast cancer patients; Anthracyclines; Angiogenesis; p53 status; Potential prognostic factors
ID Early breast cancer patients; Anthracyclines; Angiogenesis; p53 status; Potential prognostic factors
AB A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤214.8 microvesells/ mm2) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm2). The proportion of higher MVD tumors significantly increased in N2 (P00.000) and in estrogen (P00.046) or progesterone receptors (P00.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P00.000), steroid receptors negativity (P00.000), cytokeratin5/ 6 positivity (P00.026), topoisomerase IIα overexpression (P00.005) and higher proliferation rate (P00.001). In univariate analysis, higher MVD (P00.016) and p53 negativity (P00.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.
C1 [Biesaga, Beata] Centre of Oncology, Department of Applied Radiobiology, Garncarska 11, 31-115 Krakow, Poland.
[Niemiec, Joanna] Centre of Oncology, Department of Applied Radiobiology, Garncarska 11, 31-115 Krakow, Poland.
[Ziobro, Marek] Centre of Oncology, Department of Medical Oncology, Garncarska 11, 31-115 Krakow, Poland.
RP Biesaga, B (reprint author), Centre of Oncology, Department of Applied Radiobiology, 31-115 Krakow, Poland.
EM z5biesag@cyfronet.pl
CR Early Breast Cancer Trialists' Collaborative Group, EBCTCG,, 2005, Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–717
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Biesaga B, Niemiec J, Ziobro M, Wysocka J, Kruczak A, 2011, Prognostic potential of topoisomerase IIα and HER2 in a retrospective analysis of early advanced breast cancer patients treated with adjuvant anthracycline chemotherapy. Breast 20(4):338–350
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 949
EP 960
DI 10.1007/s12253-012-9525-9
PG 12
ER
PT J
AU Kulkarni, A
Thota, B
Mallavarapu, RS
Thennarasu, K
Arivazhagan, A
Santosh, V
Chandramouli, AB
AF Kulkarni, Aniruddh
Thota, Balaram
Mallavarapu, R Srividya
Thennarasu, Kandavel
Arivazhagan, Arimappamagan
Santosh, Vani
Chandramouli, Ashwathnarayanara Bangalore
TI Expression Pattern and Prognostic Significance of IGFBP Isoforms in Anaplastic Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anaplastic astrocytoma; Insulin-like growth factor binding protein; Immunohistochemistry; Prognosis
ID Anaplastic astrocytoma; Insulin-like growth factor binding protein; Immunohistochemistry; Prognosis
AB The role of insulin- like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in recent years. There is paucity of literature on their expression and impact on clinical outcome in anaplastic astrocytomas. To evaluate the expression patterns of IGFBP isoforms in anaplastic astrocytoma and correlate with clinical outcome, a retrospective study of 53 adult patients operated for supratentorial lobar anaplastic astrocytoma was performed. The protein expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7), was studied by immunohistochemistry on all samples. The patients were followed up and outcome was documented. The median age at presentation in the present study was 35 years. The pattern of staining was intra cytoplasmic, homogenous and diffuse for IGFBP-2, -3 and -5 and granular for IGFBP-7. IGFBP-2 expression was significantly low in anaplastic astrocytoma as compared to other isoforms (P<0.001). IGFBP-3 expression was higher than the other isoforms. However, its’ expression correlated with favorable overall survival and demonstrated a trend towards significance on univariate analysis. The present study is the first of its kind to describe comprehensively the pattern of expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7) in anaplastic astrocytomas. IGFBP-2 and IGFBP-3 expression patterns and correlation to prognosis were distinct in anaplastic astrocytoma patients, contradictory to what has been reported in glioblastoma, thus giving further evidence that anaplastic astrocytomas are molecularly distinct from glioblastoma.
C1 [Kulkarni, Aniruddh] National Institute of Mental Health and Neurosciences, Department of NeurosurgeryBangalore, India.
[Thota, Balaram] National Institute of Mental Health and Neurosciences, Department of NeuropathologyBangalore, India.
[Mallavarapu, R Srividya] National Institute of Mental Health and Neurosciences, Department of NeuropathologyBangalore, India.
[Thennarasu, Kandavel] National Institute of Mental Health and Neurosciences, Department of BiostatisticsBangalore, India.
[Arivazhagan, Arimappamagan] National Institute of Mental Health and Neurosciences, Department of NeurosurgeryBangalore, India.
[Santosh, Vani] National Institute of Mental Health and Neurosciences, Department of NeuropathologyBangalore, India.
[Chandramouli, Ashwathnarayanara Bangalore] National Institute of Mental Health and Neurosciences, Department of NeurosurgeryBangalore, India.
RP Santosh, V (reprint author), National Institute of Mental Health and Neurosciences, Department of Neuropathology, Bangalore, India.
EM vani.santosh@gmail.com
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Wang H, Fuller GN, Zhang W, 2004, Insulin-like growth factors and insulin-like growth factors binding proteins in CNS tumors. In: Zhang W, Fuller GN, eds, Genomic and molecular neurooncology. Jones and Bartlett Publishers, Sudbury, pp 119–130
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Moore LM, Holmes KM, Smith SM, Wu Y, Tchougounova E, Uhrbom L et al, 2009, IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas. Proc Natl Acad Sci U S A 106(39):16675–16679
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Hou XJ, Zhang YZ, Liu X, Meng LH, Qiao YB, 2009, Expressions of IGFBP-5, cFLIP in cervical intraepithelial neoplasia, cervical carcinoma and their clinical significances: a molecular pathology. J Exp Clin Cancer Res 28:70
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 961
EP 967
DI 10.1007/s12253-012-9526-8
PG 7
ER
PT J
AU Ye, F
Jiao, J
Zhou, C
Cheng, Q
Chen, H
AF Ye, Feng
Jiao, Jie
Zhou, Caiyun
Cheng, Qi
Chen, Huaizeng
TI Nucleotide Excision Repair Gene Subunit XPD is Highly Expressed in Cervical Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE XPD; Cervical squamous cell carcinoma; Nucleotide excision repair
ID XPD; Cervical squamous cell carcinoma; Nucleotide excision repair
AB One of the subunits in the mammalian transcription factor IIH complex,XPD (TFIIH p80), plays a significant role in the nucleotide excision repair pathway. Events such as abnormal DNA excision repair may be involved in the cervical carcinogenesis process. Expression of the human XPD protein was examined using immunohistochemistry in 84 normal cervical tissues and 148 cervical squamous cell carcinoma samples. Additionally, qRT-PCR was performed to analyse the XPD mRNA expression in 69 fresh normal cervical tissues and 110 cervical carcinoma samples. The relationships between XPD expression and various clinicopathological features (including age, FIGO stage, tumor size, stroma involvement, lymph node metastasis and histologic grade) were assessed. The XPD (TFIIH p80) protein was detected primarily in the cytoplasm.We found a statistically significant difference in XPD expression level in cervical carcinoma versus normal cervical tissue (Z0−7.302, P<0.000). Notably, XPD mRNA was significantly over-expressed in cervical carcinoma tissues but not in normal cervix tissues (t06.942, P<0.000). However, no statistically significant relationship was found regarding XPD expression and age, FIGO stage, tumor size, stroma involvement, lymph node metastasis or histologic grade (P< 0.089, 0.953, 0.809, 0.275, 0.421, 0.387 respectively). Our results showed that XPD was highly expressed in cervical squamous cell carcinoma tissues. A poorly understood change may occur during the XPD transcription process, resulting in the abnormal enrichment seen from mRNA to the protein level, thus leaving the protein unable to perform the normal function of excision repair. There is a need for further research in order to elucidate the specific mechanism involved.
C1 [Ye, Feng] School of Medicine, Zhejiang University, Women’s Hospital, Women’s Reproductive Health Laboratory of Zhejiang Province, Xueshi Rd #2, 310006 Hangzhou, China.
[Jiao, Jie] School of Medicine, Zhejiang University, Women’s Hospital, Department of Gynecological Oncology, Xueshi Rd #2, 310006 Hangzhou, China.
[Zhou, Caiyun] School of Medicine, Zhejiang University, Women’s Hospital, Department of Pathology, Xueshi Rd #2, 310006 Hangzhou, China.
[Cheng, Qi] School of Medicine, Zhejiang University, Women’s Hospital, Women’s Reproductive Health Laboratory of Zhejiang Province, Xueshi Rd #2, 310006 Hangzhou, China.
[Chen, Huaizeng] School of Medicine, Zhejiang University, Women’s Hospital, Women’s Reproductive Health Laboratory of Zhejiang Province, Xueshi Rd #2, 310006 Hangzhou, China.
RP Chen, H (reprint author), School of Medicine, Zhejiang University, Women’s Hospital, Women’s Reproductive Health Laboratory of Zhejiang Province, 310006 Hangzhou, China.
EM chenhz@zju.edu.cn
CR Wang J, Lv XW, Shi JP et al, 2007, Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells. World J Gastroenterol 13:1129–1134
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Falik-Zaccai TC, Keren Z, Slor H, 2009, The Versatile DNA Nucleotide Excision Repair, NER, and Its Medical Significance. Pediatr Endocrinol Rev 7:117–122
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He X, Ye F, Zhang J et al, 2008, Susceptibility of XRCC3, XPD, and XPG genetic variants to cervical carcinoma. Pathobiology 75:356–363
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Jaitovich-Groisman I, Benlimame N, Slagle BL et al, 2001, Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. J Bio Chem 276:14124–14132
Oksenych V, Coin F, 2010, The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell Cycle 9:90–96
Gao W, Romkes M, Zhong S et al, 2010, Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk. Oncol Rep 24:257–262
Sturgis EM, Zheng R, Li L et al, 2000, XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case–control analysis. Carcinogenesis 21:2219–2223
Butkiewicz D, Rusin M, Enewold L et al, 2001, Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22:593–597
Vogel U, Hedayati M, Dybdahl M et al, 2001, Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited. Carcinogenesis 22:899–904
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Aboussekhra A, Biggerstaff M, Shivji MK et al, 1995, Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell 80:859–868
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 969
EP 975
DI 10.1007/s12253-012-9527-7
PG 7
ER
PT J
AU Kovacs, J
Gurzu, S
Jung, J
Szederjesi, J
Copotoiu, SM
Copotoiu, R
Azamfirei, L
AF Kovacs, Judit
Gurzu, Simona
Jung, Janos
Szederjesi, Janos
Copotoiu, Sanda-Maria
Copotoiu, Ruxandra
Azamfirei, Leonard
TI Clinico-Pathological Particularities of the Shock- Related Pancreatitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute pancreatitis; Analgo-sedation; Hyperglycemia; Hypocalcemia; Severe hypotension
ID Acute pancreatitis; Analgo-sedation; Hyperglycemia; Hypocalcemia; Severe hypotension
AB Acute pancreatitis can develop in patients with shock due to the underlying diseases, surgical interventions or because of severe hypoperfusion. The aim of our work was to study the histological alterations of the pancreas in patients dying after cardiogenic, hypovolemic or septic shock, to demonstrate the presence and severity of pancreatic injury. We performed a retrospective study which included patients who died and who were autopsied after different types of shock, hospitalized between 2007–2009 in general and cardiac intensive care units. We excluded the patients with known pancreatic diseases. From 223 patients included in our study 39 presented necrotising hemorrhagic alteration of the pancreatic tissue. There were no differences in histological and immunohistochemical findings between the different etiopathogenetic types of shock. None of the patients had characteristic clinical signs for acute pancreatitis. The digestive symptoms, they presented, could be related to the underlying disease or to postoperative state. The common findings in these patients were prolonged and severe hypotension, associated renal dysfunction, leucocytosis, hyperglycemia and hypocalcemia. Pancreatitis can occur in patients with shock, due to prolonged hypoperfusion of the pancreas. It is difficult to diagnose it because clinical signs are altered due to severity of underlying disease or analgo-sedation commonly used in intensive care. We therefore recommend in patients with shock to consider the possible development of ischemic pancreatitis for prompt and efficient treatment.
C1 [Kovacs, Judit] University of Medicine and Pharmacy Tg-Mures, Department of Anesthesia and Intensive CareTargu-Mures, Romania.
[Gurzu, Simona] University of Medicine and Pharmacy Targu-Mures, Department of Pathology, Gheorghe Marinescu 38, 540193 Targu-Mures, Romania.
[Jung, Janos] University of Medicine and Pharmacy Targu-Mures, Department of Pathology, Gheorghe Marinescu 38, 540193 Targu-Mures, Romania.
[Szederjesi, Janos] University of Medicine and Pharmacy Tg-Mures, Department of Anesthesia and Intensive CareTargu-Mures, Romania.
[Copotoiu, Sanda-Maria] University of Medicine and Pharmacy Tg-Mures, Department of Anesthesia and Intensive CareTargu-Mures, Romania.
[Copotoiu, Ruxandra] University of Medicine and Pharmacy Tg-Mures, Department of Anesthesia and Intensive CareTargu-Mures, Romania.
[Azamfirei, Leonard] University of Medicine and Pharmacy Tg-Mures, Department of Anesthesia and Intensive CareTargu-Mures, Romania.
RP Gurzu, S (reprint author), University of Medicine and Pharmacy Targu-Mures, Department of Pathology, 540193 Targu-Mures, Romania.
EM simonagurzu@yahoo.com
CR Piton G, Barbot O, Manzon C et al, 2010, Acute ischemic pancreatitis following cardiac arrest: a case report. J Pancreas, Online, 11(5):456–459
Hackert T, Hartwig W, Fritz S et al, 2009, Ischemic acute pancreatitis: clinical features of 11 patients and review of the literature. Am J Surg 197(4):450–454
Sakorafas GH, Tsiotos GG, Sarr MG, 2000, Ischemia/reperfusion induced pancreatitis. Dig Surg 17:3–14
Schmitz-Moorman P, 1981, Comparative radiological and morphological study of the human pancreas. Acute necrotising pancreatitis in man. Path Res Pract 171:325–335
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Kuo IM, Wang F, Liu KH et al, 2009, Post-gastrectomy acute pancreatitis in a patient with gastric carcinoma and pancreas divisum. World J Gastroenterol 15(36):4596–4600
Blom RLGM, van Heijl M, Busch ORC et al, 2009, Acute pancreatitis in the postoperative course after esophagectomy: a major complication described in 4 patients. Case Rep Gastroenterol 3:382–388
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 977
EP 981
DI 10.1007/s12253-012-9528-6
PG 5
ER
PT J
AU Wu, L
Wang, Z
Lu, R
Jiang, W
AF Wu, Lielin
Wang, Zhiming
Lu, Rongli
Jiang, Wei
TI Expression of High Mobility Group A2 is Associated with Poor Survival in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
C1 [Wu, Lielin] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
[Wang, Zhiming] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
[Lu, Rongli] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Jiang, Wei] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
RP Wang, Z (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
EM wzm005@yahoo.com.cn
CR Srivatanakul P, Sriplung H, Deerasamee S, 2004, Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev 5:118–125
Mann CD, Neal CP, Garcea G et al, 2007, Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer 43:979–992
Reeves R, Beckerbauer L, 2001, HMGI/Y proteins: flexible regulators of transcription and chromatin structure. Biochim Biophys Acta 1519:13–29
Fusco A, Fedele M, 2007, Roles of HMGA proteins in cancer. Nat Rev Cancer 7:899–910
Cleynen I, Van de Ven WJ, 2008, The HMGA proteins: a myriad of functions. Int J Oncol 32:289–305
Chiappetta G, Avantaggiato V, Visconti R et al, 1996, High level expression of the HMGI, Y, gene during embryonic development. Oncogene 13:2439–2446
Rogalla P, Drechsler K, Frey G et al, 1996, HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. Am J Pathol 149:775–779
Ashar HR, Fejzo MS, Tkachenko A et al, 1995, Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell 82:57–65
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Sarhadi VK, Wikman H, Salmenkivi K et al, 2006, Increased expression of high mobility group A proteins in lung cancer. J Pathol 209:206–212
Meyer B, Loeschke S, Schultze A et al, 2007, HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog 46:503– 511
Abe N, Watanabe T, Suzuki Y et al, 2003, An increased highmobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue. Br J Cancer 89:2104– 2109
Belge G, Meyer A, Klemke M et al, 2008, Upregulation of HMGA2 in thyroid carcinomas: a novel molecular marker to distinguish between benign and malignant follicular neoplasias. Gene Chromosome Canc 47:56–63
Motoyama K, Inoue H, Nakamura Y et al, 2008, Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 14:2334– 2340
Livak KJ, Schmittquen TD, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T), Method. Method 25:402–408
Miyazawa J, Mitoro A, Kawashiri S et al, 2004, Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Cancer Res 64:2024–2029
Park S-M, Shell S, Radjabi AR et al, 2007, Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle 6:2585–2590
Hristov AC, Cope L, Reyes MD et al, 2009, HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mod Pathol 22:43–49
Vallone D, Battista S, Pierantoni GM et al, 1997, Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product. EMBO J 16:5310–5321
Fedele M et al, 2006, HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity. Cancer Cell 9:459–471
Thuault S, Valcourt U, Petersen M et al, 2006, Transforming growth factor employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 174:175–183
Wang X, Liu X, Li AY et al, 2011, Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers. Clin Cancer Res 17:2570–2580
Langelotz C, Schmid P, Jakob C et al, 2003, Expression of highmobility- group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer. Br J Cancer 88:1406–1410
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 983
EP 987
DI 10.1007/s12253-012-9514-z
PG 5
ER
PT J
AU Gong, L
Cai, Y
Zhou, X
Yang, H
AF Gong, Liang
Cai, Yun
Zhou, Xiangdong
Yang, Heping
TI Activated Platelets Interact with Lung Cancer Cells Through P-Selectin Glycoprotein Ligand-1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Platelet activation; P-selectin; Pselectin glycoprotein ligand 1; RNA interference
ID Lung cancer; Platelet activation; P-selectin; Pselectin glycoprotein ligand 1; RNA interference
AB Hematogenous metastasis always leads to the poor prognosis of non-small cell lung cancers (NSCLC). Activated platelets are involved in hematogenous metastasis and may be a potential therapeutic target. P-selectin is an important adhesion molecule and expressed on the surface of activated platelets. P-selectin glycoprotein ligand-1 (PSGL-1) as a transmembrane protein is expressed on the surface of various cell types. P-selectin can bind to PSGL-1, and thereby initiate the platelet-mediated cell adhesion. The aim of the study was to investigate the degree of platelet activation in NSCLC and the roles of PSGL-1 in the activation of platelets. Purified platelets were obtained from NSCLC patients (40 lung adenocarcinomas and 26 lung squamous cell carcinomas), and P-selectin expression was detected by fluorescence-activated cell sorter. The population of peripheral blood platelets with P-selectin expression in lung adenocarcinoma was 63.16±25.44 %, and significantly higher than that in lung squamous cell carcinoma (35.97±17.19 %) and the healthy population (9.12± 7.66 %, n030). A specific small hairpin RNA (shRNA) for PSGL-1 was transfected into A549 human alveolar cell carcinoma cells. The expressions of PSGL-1 mRNA and protein were significantly reduced with the PSGL-1 shRNA (p<0.01). Furthermore, the knockdown of PSGL-1 also resulted in the significantly reduced aggregate formation of activated platelets and A549 cells. Thus, activated platelets may interact with lung cancer cells through PSGL-1. Inhibiting platelet activation and/or down-regulating PSGL-1 expression may be useful for suppression of tumor metastasis.
C1 [Gong, Liang] the Third Military Medical University, Southwest Hospital, Department of Respiratory diseasesChongqing, China.
[Cai, Yun] the Third Military Medical University, Southwest Hospital, Southwest Cancer InstituteChongqing, China.
[Zhou, Xiangdong] the Third Military Medical University, Southwest Hospital, Department of Respiratory diseasesChongqing, China.
[Yang, Heping] the Third Military Medical University, Southwest Hospital, Department of Respiratory diseasesChongqing, China.
RP Yang, H (reprint author), the Third Military Medical University, Southwest Hospital, Department of Respiratory diseases, Chongqing, China.
EM mkojima@163.com
CR Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ, 2007, Cancer statistics. CA Cancer J Clin 57:43–66
Inamura K, Ishikawa Y, 2010, Lung cancer progression and metastasis from the prognostic point of view. Clin ExpMetastasis 27:389–397
Geiger TR, Peeper DS, 2009, Metastasis mechanisms. Biochim Biophys Acta 1796:293–308
Joyce JA, Pollard JW, 2009, Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252
Borsig L, 2008, The role of platelet activation in tumor metastasis. Expert Rev Anticancer Ther 8:1247–1255
Sierko E, Wojtukiewicz MZ, 2007, Inhibition of platelet function, does it offer a chance of better cancer progression control? Semin Thromb Hemost 33:712–721
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 989
EP 996
DI 10.1007/s12253-012-9531-y
PG 8
ER
PT J
AU Roszak, A
Mostowska, A
Sowinska, A
Lianeri, M
Jagodzinski, PP
AF Roszak, Andrzej
Mostowska, Adrianna
Sowinska, Anna
Lianeri, Margarita
Jagodzinski, P Pawel
TI Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical carcinoma; IL12A and IL12B; Polymorphisms
ID Cervical carcinoma; IL12A and IL12B; Polymorphisms
AB We studied the contribution of the IL12A 3′UTR G>A (rs568408) and IL12B 3′UTR A>C (rs3212227) polymorphisms to the risk of cervical cancer. These polymorphisms were genotyped in four hundred-five patients with cervical cancer and four hundred fifty unrelated healthy females from the Polish population. Logistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status revealed that the IL12B 3′UTR A>C polymorphism could be a genetic risk factor for cervical cancer. The adjusted odds ratio (OR) for patients with the A/C genotype vs A/A genotype was 1.557 (95 % CI01.173–2.066, p00.0178) and adjusted OR for the C/C or A/C genotype vs the A/A genotype was 1.635 (95 % CI01.241–2.153, p00.0125). However, logistic regression analysis did not show an association of the IL12A 3′UTR G>A polymorphism with cervical cancer development in the studied Polish population. Our studies confirmed that the IL12B 3′UTR A>C polymorphism may be a genetic risk factor for cervical cancer.
C1 [Roszak, Andrzej] Greater Poland Cancer Center, Department of Radiotherapy and Gynecological OncologyPoznan, Poland.
[Mostowska, Adrianna] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Sowinska, Anna] Poznan University of Medical Sciences Poznan, Department of Computer Science and StatisticsPoznan, Poland.
[Lianeri, Margarita] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Jagodzinski, P Pawel] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
RP Jagodzinski, PP (reprint author), Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznan, Poland.
EM pjagodzi@am.poznan.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 997
EP 1002
DI 10.1007/s12253-012-9532-x
PG 6
ER
PT J
AU Hanajiri, R
Ohashi, K
Hirashima, Y
Kakihana, K
Kobayashi, T
Yamashita, T
Sakamaki, H
Akiyama, H
AF Hanajiri, Ryo
Ohashi, Kazuteru
Hirashima, Yuka
Kakihana, Kazuhiko
Kobayashi, Takeshi
Yamashita, Takuya
Sakamaki, Hisashi
Akiyama, Hideki
TI Second Allogeneic Transplantation for Relapsed Acute Leukemia after Initial Allogeneic Hematopoietic Stem Cell Transplantation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Second allogeneic hematopoietic stem cell transplantation; Acute leukemia; Relapse; Salvage treatment
ID Second allogeneic hematopoietic stem cell transplantation; Acute leukemia; Relapse; Salvage treatment
AB We retrospectively reviewed the medical records of 45 patients with relapsed acute leukemia after initial allogeneic hematopoietic stem ell transplantation (allo-HSCT). Among 45 patients, a total of 11 patients eventually underwent second allo-HSCT (HSCT-2). Median survival after relapse was 294 days (range, 135–942 days) for HSCT-2. Multivariate analysis showed significantly better survival for recipients of second allo-HSCT than for other patients (hazard ratio, 4.38; 95 % confidence interval, 1.45–13.2; P00.009). Although outcomes for patients with relapsed leukemia were generally poor, our results suggest that second HSCT could offer a survival advantage over other conventional salvage strategies.
C1 [Hanajiri, Ryo] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Hirashima, Yuka] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center, Pharmacy DivisionTokyo, Japan.
[Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashi, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Yamashita, Takuya] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Akiyama, Hideki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Ohashi, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM k.ohashi@cick.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1003
EP 1008
DI 10.1007/s12253-012-9535-7
PG 6
ER
PT J
AU Lv, H
Li, Q
Qiu, W
Xiang, J
Wei, H
Liang, H
Sui, A
Liang, J
AF Lv, Hongying
Li, Qicai
Qiu, Wengsheng
Xiang, Jinyu
Wei, Hongjun
Liang, Hua
Sui, Aihua
Liang, Jun
TI Genetic Polymorphism of XRCC1 Correlated with Response to Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal neoplasms/genetics; Polymorphism; Oxaliplatin/drug therapy; X-ray repair cross complementing 1/genetics
ID Colorectal neoplasms/genetics; Polymorphism; Oxaliplatin/drug therapy; X-ray repair cross complementing 1/genetics
AB To examine the association between genetic polymorphisms of XRCC1 Arg399Gln(G→A) and response to oxaliplatin-based chemotherapy in advanced colorectal cancer. XRCC1 genotypes of totally 99 patients(37 stage III, 62 stage IV)with advanced colorectal cancer treated with oxaliplatin-based chemotherapy were detected by TaqMan-MGB probe allelic discrimination method. And clinical response of 62 patients in stage IV after 2 to 3 cycles of chemotherapy were evaluated. Also time to progress (TTP) of all patients were evaluated. Of the genotype frequencies in all patients, up to 52.53 % were G/G genotype, 9.09 % were A/A genotype, and 38.38 % were G/A genotype. The response rate (CR+PR) of 62 patients in stage IV was 61.29% (19/31). Patients with G/G genotype showed enhanced respond to chemotherapy compared to those with G/A+A/A (x205.6, P00.029; OR03.845, 95 %CI01.231~12.01, P00.018). Individuals with the G/G genotype had a TTP of 10.0 (8.88–11.12) months, those with the G/A+A/A genotype had an TTP of 5.0(4.26–5.74) months. The log-rank test was marginally significant (x2029.20, P<0.01). The Cox proportional hazards model, adjusted for stage, performance status, and chemotherapy regimen, showed that only XRCC1 G/G genotypes increases the OR significantly (OR03.555; 95 % CI, 2.119~5.963; P<0.01). The results suggest that XRCC1 Arg399Gln polymorphisms is associated with the response to oxaliplantin-based chemotherapy and time to progression in advanced colorectal cancer in Chinese population. It is proposed that the XRCC1 Arg399Gln polymorphism should be routinely detected to screen patients who are more likely benefit from oxaliplantin-based treatment.
C1 [Lv, Hongying] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
[Li, Qicai] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
[Qiu, Wengsheng] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
[Xiang, Jinyu] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
[Wei, Hongjun] Qingdao Municipal Hospital, Department of Pathology, 266027 Qingdao, CN, China.
[Liang, Hua] Qingdao Oncology Hospital, Department of Oncology, 266074 Qingdao, CN, China.
[Sui, Aihua] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
[Liang, Jun] The Affiliated Hospital of Qingdao University, 266003 Qingdao, CN, China.
RP Liang, J (reprint author), The Affiliated Hospital of Qingdao University, 266003 Qingdao, China.
EM qdliangjun@163.com
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Zhang Z, Miao XP, Tan W, Guo YL, Zhang XM, Lin DX, 2006, Correlation of genetic polymorphisms in DNA repair genes ADPRT and XRCC1 to risk of gastric cancer. Ai Zheng 25(1):7–10
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1009
EP 1014
DI 10.1007/s12253-012-9536-6
PG 6
ER
PT J
AU Sobczuk, A
Poplawski, T
Blasiak, J
AF Sobczuk, Anna
Poplawski, Tomasz
Blasiak, Janusz
TI Polymorphisms of DNA Repair Genes in Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE XRCC1; ERCC2; hOGG1; Endometrial cancer; RFLP-PCR; BER; NER
ID XRCC1; ERCC2; hOGG1; Endometrial cancer; RFLP-PCR; BER; NER
AB Endometrial cancer belongs to the commonest malignancy in females. Its development may be associated with the high exposure of endometrium to exo- and endogenous estrogens. Estrogens produce DNA bulky adducts and oxidative base damages which are removed in nucleotide excision repair (NER) and base excision repair (BER) pathways. The reaction of endometrial cells to DNA damage may be crucial for their susceptibility to cancer transformation. This reaction is executed mainly by DNA repair, which can be modulated by the variability in the genes encoding DNA repair proteins. In this report we genotyped 4 polymorphisms of 3 DNA repair genes in 94 endometrial cancer patients and 114 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: p.Arg194Trp, p.Arg399Gln of the XRCC1 gene, p.Ser326Cys of the hOGG1 gene and p.Lys751Gln of the ERCC2 gene. We found an association between the ERCC2 751Gln variant and endometrial cancer occurrence (OR 3.95; 95 % CI 1.88–8.31). Gene-gene interaction between the ERCC2 751Gln and XRCC1 194Trp variants also increased the risk of endometrial cancer (OR 4.41; 95 % CI 2.01–9.67). The risk in the carriers of the ERCC2 751Gln variant was increased by a positive cancer history in first degree relatives (OR 4.97; 95 % CI 1.98–12.48). The risk of endometrial cancer was not alter by polymorphism p.Ser326Cys of the hOGG1 gene. The 751 Lys/Gln polymorphism of the ERCC2 gene may be linkedwith endometrial cancer occurrence and its effect can be potentiated by variants of the XRCC1 gene or first degree relatives positive cancer history.
C1 [Sobczuk, Anna] Medical University of Lodz, Department of Gynaecology and ObstetricsLodz, Poland.
[Poplawski, Tomasz] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Blasiak, Janusz] University of Lodz, Department of Molecular GeneticsLodz, Poland.
RP Blasiak, J (reprint author), University of Lodz, Department of Molecular Genetics, Lodz, Poland.
EM jblasiak@biol.uni.lodz.pl
CR Prat J, Gallardo A, Cuatrecasas M, Catasus L, 2007, Endometrial carcinoma: pathology and genetics. Pathology 39:72–87
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Velasco A, Bussaglia E, Pallares J et al, 2006, PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 37:1465–1472
Liehr JG, Fang WF, Sirbasku DA, Ari-Ulubelen A, 1986, Carcinogenicity of catechol estrogens in Syrian hamsters. J Steroid Biochem 24:353–356
Kohno T, Kunitoh H, Toyama K et al, 2006, Association of the OGG1-Ser326Cys polymorphism with lung adenocarcinoma risk. Cancer Sci 97:724–728
Pachouri SS, Sobti RC, Kaur P, Singh J, 2007, Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol 26:186–191
Poplawski T, Arabski M, Kozirowska D et al, 2006, DNA damage and repair in gastric cancer–a correlation with the hOGG1 and RAD51 genes polymorphisms. Mutat Res 601:83–91
Yin J, Vogel U, Ma Y, Qi R, Sun Z, Wang H, 2007, The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population. Lung Cancer 56:153–160
Hatt L, Loft S, Risom L et al, 2008, OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study. Mutat Res 639:45–54
Yin J, Vogel U, Ma Y, Guo L,Wang H, Qi R, 2006, Polymorphism of the DNA repair gene ERCC2 Lys751Gln and risk of lung cancer in a northeastern Chinese population. Cancer Genet Cytogenet 169:27–32
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Brewster AM, Jorgensen TJ, Ruczinski I et al, 2006, Polymorphisms of the DNA repair genes ERCC2, Lys751Gln, and XRCC1, Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer. Breast Cancer Res Treat 95:73–80
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1015
EP 1020
DI 10.1007/s12253-012-9537-5
PG 6
ER
PT J
AU Chuangui, Ch
Peng, T
Zhentao, Y
AF Chuangui, Chen
Peng, Tang
Zhentao, Yu
TI The Expression of High Mobility Group Box 1 is Associated with Lymph Node Metastasis and Poor Prognosis in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE High mobility group box 1 (HMGB1); Esophageal squamous cell carcinoma (ESCC); Vascular endothelial growth factor C (VEGF-C); Lymphangiogenesis
ID High mobility group box 1 (HMGB1); Esophageal squamous cell carcinoma (ESCC); Vascular endothelial growth factor C (VEGF-C); Lymphangiogenesis
AB The objective is to explore the expression of high mobility group box 1 (HMGB1) in esophageal squamous cell carcinoma (ESCC) and its relationship with lymph node metastasis and the prognosis of patients as well as possible mechanism. The expression of HMGB1, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in ESCC tissues, which were obtained from 72 patients who underwent radical esophagectomy, was detected through immunohistochemistry, firstly. The correlations between HMGB1 and VEGF-C, and micro-lymphatic vessel density (MLD), and lymph node metastasis, and the prognosis of patients, were analyzed by statistic analysis. The plasmid of small interference RNA (siRNA) targeting HMGB1, giving siHMGB1, was transfected into exponentially growing KYSE150 human esophageal squamous cancer cells and the expression of HMGB1 mRNA and protein was observed by Real-time PCR and Western Blot and the expression of VEGF-C was examined by ELISA. HMGB1 expressed highly in the nuclei and cytoplasm of carcinoma cells as well as the extracellular space in ESCC and was associated with lymph node metastasis, MLD, the expression of VEGF-C, TNM stage and the prognosis of patients (P<0.05 or P<0.01). In vitro, siHMGB1 inhibited the expression of HMGB1 mRNA and protein and the secretion of VEGF-C in KYSE150 cells. In ESCC, HMGB1 expresses highly and affects the prognosis of patients through regulating the expression of VEGF-C to promote lymphangiogenesis and lymph node metastasis, and HMGB1 might serve as the marker of progression and potential target for anti-lymphangiogenesis therapy.
C1 [Chuangui, Chen] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
[Peng, Tang] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
[Zhentao, Yu] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
RP Zhentao, Y (reprint author), Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
EM tracycheng2008@yahoo.com.cn
CR Duff SE, Li C, Jeziorska M, Kumar S, Saunders MP, Sherlock D, O’Dwyer ST, Jayson GC, 2003, Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy. Br J Cancer 89:426–30
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Liu P, Chen W, Zhu H, Liu B, Song S, Shen W, Wang F, Tucker S, Zhong B, Wang D, 2009, Expression of VEGF-C correlates with a poor prognosis based on analysis of prognostic factors in 73 patients with esophageal squamous cell carcinomas. Jpn J Clin Oncol 39:644–50
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Ito N, DeMarco RA,Mailliard RB, Han J, Rabinowich H, Kalinski P, Stolz DB, Zeh HJ 3rd, Lotze MT, 2007, Cytolytic cells induce HMGB1 release from melanoma cell lines. J Leukoc Biol 81:75–83
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1021
EP 1027
DI 10.1007/s12253-012-9539-3
PG 7
ER
PT J
AU Palanimuthu, D
Baskaran, N
Silvan, S
Rajasekaran, D
Manoharan, Sh
AF Palanimuthu, Duraisamy
Baskaran, Nagarethinam
Silvan, Simon
Rajasekaran, Duraisamy
Manoharan, Shanmugam
TI Lupeol, A Bioactive Triterpene, Prevents Tumor Formation During 7,12-Dimethylbenz(a)anthracene Induced Oral Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Antioxidants; DMBA; Lipid peroxidation; Lupeol; Oral cancer
ID Antioxidants; DMBA; Lipid peroxidation; Lupeol; Oral cancer
AB The oral cancer chemopreventive efficacy of lupeol, a bioactive triterpene, was assessed by monitoring the tumor incidence and using the status of phase I and II xenobiotic metabolizing enzymes, lipid peroxidation and antioxidants as biochemical end points during 7,12-dimethylbenz( a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA three times a week for 14 weeks. Well differentiated oral squamous cell carcinoma with marked abnormalities in the status of biochemical markers were noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely inhibited the formation of oral tumors and restored the status of biochemical markers during DMBA induced oral carcinogenesis. The present study thus demonstrates the chemopreventive potential of lupeol in DMBA induced oral carcinogenesis. The chemopreventive potential of lupeol is probably due to its antioxidant or free radical scavenging property and modulating effect on phase I and II xenobiotic metabolizing enzymes in favour of the excretion of carcinogenic metabolites during DMBA induced hamster buccal pouch carcinogenesis.
C1 [Palanimuthu, Duraisamy] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai nagar, 608 002 Tamil Nadu, India.
[Baskaran, Nagarethinam] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai nagar, 608 002 Tamil Nadu, India.
[Silvan, Simon] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai nagar, 608 002 Tamil Nadu, India.
[Rajasekaran, Duraisamy] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai nagar, 608 002 Tamil Nadu, India.
[Manoharan, Shanmugam] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai nagar, 608 002 Tamil Nadu, India.
RP Manoharan, Sh (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
EM sakshiman@rediffmail.com
CR Rastogi T, Devesa S, Mangtani P, Mathew A, Cooper N, Kao R, Sinha R, 2008, Cancer incidence rates among South Asians in four geographic regions: India, Singapore, UK and US. Int J Epidemiol 37:147–160
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Yamashita K, Lu H, Lu J, Chen G, Yokoyama T, Sagara Y, Manabe M, Kodama H, 2002, Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin Chim Acta 325:91–6
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1029
EP 1037
DI 10.1007/s12253-012-9541-9
PG 9
ER
PT J
AU Li, B
Ge, Z
Song, Sh
Zhang, Sh
Yan, H
Huang, B
Zhang, Y
AF Li, Bing
Ge, Zhiping
Song, Shipeng
Zhang, Shengbin
Yan, Hong
Huang, Boyun
Zhang, Yangde
TI Decreased Expression of SOX7 is Correlated with Poor Prognosis in Lung Adenocarcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; SOX7; Immunohistochemistry; Quantitative real-time reverse transcription polymerase chain reaction; Prognosis
ID Lung adenocarcinoma; SOX7; Immunohistochemistry; Quantitative real-time reverse transcription polymerase chain reaction; Prognosis
AB Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/β-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/β- catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P<0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P00.002), lymph node metastasis (P00.011) and advanced TNM stage (P00.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P00.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P00.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma.
C1 [Li, Bing] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87Changsha, Hunan, China.
[Ge, Zhiping] the Third Affiliated Hospital of Inner Mongolia Medical College (Baogang Hospital of Inner Mongolia), Department of Cardiology, Shaoxian Road 20, Kun DistrictBaotou, Inner Mongolia, China.
[Song, Shipeng] the Third Affiliated Hospital of Inner Mongolia Medical College (Baogang Hospital of Inner Mongolia), Department of Genery Surgery, Shaoxian Road 20, Kun DistrictBaotou, Inner Mongolia, China.
[Zhang, Shengbin] the Third Affiliated Hospital of Inner Mongolia Medical College (Baogang Hospital of Inner Mongolia), Department of Genery Surgery, Shaoxian Road 20, Kun DistrictBaotou, Inner Mongolia, China.
[Yan, Hong] the second Affiliated Hospital of Baotou Medical College, Department of CardiologyBaotou, Inner Mongolia, China.
[Huang, Boyun] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87Changsha, Hunan, China.
[Zhang, Yangde] Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Xiangya Road 87Changsha, Hunan, China.
RP Zhang, Y (reprint author), Central South University, Xiangya Hospital, National Hepatobiliary and Enteric Surgery Research Center, Changsha, China.
EM zydjs@sohu.com
CR Okamoto J, Kratz JR, Hirata T, Mikami I, Raz D, Segal M, Chen Z, Zhou HM, Pham P, Li H, Beltran A, Ray MR, Koizumi K, Shimizu K, Jablons D, He B, 2011, Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma patients. Clin Lung Cancer 12:237–44
Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, 2004, World Health Organization International Histological Classification of Tumours. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press, Lyon
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Cermenati S,Moleri S, Cimbro S, Corti P, Del Giacco L, Amodeo R, Dejana E, Koopman P, Cotelli F, BeltrameM(2008, Sox18 and Sox7 play redundant roles in vascular development. Blood 111:2657–66
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Katoh M, 2002, Expression of human SOX7 in normal tissues and tumors. Int J Mol Med 9:363–8
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1039
EP 1045
DI 10.1007/s12253-012-9542-8
PG 7
ER
PT J
AU Guo, J
Niu, R
Huang, W
Zhou, M
Shi, J
Zhang, L
Liao, H
AF Guo, JingJing
Niu, Rui
Huang, Wenhui
Zhou, Mengliang
Shi, Jixing
Zhang, Luyong
Liao, Hong
TI Growth Factors from Tumor Microenvironment Possibly Promote the Proliferation of Glioblastoma-Derived Stem-like Cells in Vitro
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma stem-like cells; Proliferation; Microenvironment; Growth factors
ID Glioblastoma stem-like cells; Proliferation; Microenvironment; Growth factors
AB Glioblastoma multiformis a lethal brain glial tumor characterized by low survival and high recurrence, partially attributed to the glioblastoma stem cells according to recent researches. Microenvironment or niche in tumor tissue is believed to provide essential support for the aberrant growth of tumor stem cells. In order to explore the effect of growth factors in tumor microenvironment on glioblastoma stem cells behavior, glioblastoma-derived stem-like cells (GDSCs) were isolated from adult human glioblastoma specimen with antibody against surface marker CD133 and were co-cultured with various tumor cells including U87MG cells, unsorted glioblastoma tumor cells, CD133- cells and normal rat primary astrocytes. Results suggested that tumor cells could promote GDSCs proliferation while non-tumor cells could not, and several growth factors were exclusively detected in the coculture system with tumor cells. It was concluded that growth factors derived from tumor microenvironment possibly contributed to the uncontrolled proliferation of GDSCs.
C1 [Guo, JingJing] China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 24# Tong Jiaxiang road, 210009 Nanjing, China.
[Niu, Rui] China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 24# Tong Jiaxiang road, 210009 Nanjing, China.
[Huang, Wenhui] China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 24# Tong Jiaxiang road, 210009 Nanjing, China.
[Zhou, Mengliang] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Shi, Jixing] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Zhang, Luyong] China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 24# Tong Jiaxiang road, 210009 Nanjing, China.
[Liao, Hong] China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 24# Tong Jiaxiang road, 210009 Nanjing, China.
RP Liao, H (reprint author), China Pharmaceutical University, Jiangsu Center for Drug Screening, Neurobiology Lab, 210009 Nanjing, China.
EM liaohong56@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1047
EP 1057
DI 10.1007/s12253-012-9543-7
PG 11
ER
PT J
AU Petrov, VS
Malkhasyan, K
Ulyanin, YM
Abdrakhmanov, FE
Khasanov, ShR
AF Petrov, V Semion
Malkhasyan, A. Karen
Ulyanin, Yurievich Mikhail
Abdrakhmanov, F E
Khasanov, Shamilyevich Rustem
TI The Value of the Preoperative FISH Test in Unscreened Bladder Cancer Patients with TUR Indications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Urothelial carcinoma; FISH; Prediction; Bladder washings
ID Bladder cancer; Urothelial carcinoma; FISH; Prediction; Bladder washings
AB Patients with bladder cancer are still requiring close follow up with frequent cystoscopies. This study aims to assess the FISH analysis, as a procedure capable of highlighting the hidden features of a tumor and helping to individualize treatment tactics. The bladder washings of 50 primary bladder cancer patients were taken prior to TURB and analyzed with the commercial FISH assay UroVysion®. All patients were divided into groups according to the maximum stage and grade of the tumor. The sensitivity of the method was 81.5 %, 91.7 % and 100 % for the Ta, T1 and T2 stage groups, respectively. For the G1, G2 and G3 groups the sensitivity was 70 %, 100 % and 100 %, respectively. In addition, the rate of detecting genetically abnormal cells was significantly higher in the T2 stage compared to the Ta and combined Ta+T1 groups, as well as in the G3 group compared to the G1 and G2 groups. The mean signal number from each chromosome insignificantly increased with the stage and grade of the tumor. The detection of <40 % genetically abnormal cells predicted the absence of muscle invasion and a G3 tumor with more then 90 % reliability. The FISH method is highly sensitive in early bladder cancer detection and is able to predict the morphological character of a tumor even before surgery.
C1 [Petrov, V Semion] Kazan Cancer CenterKazan, Russian Federation.
[Malkhasyan, A. Karen] N. N. Blokhin Russian Cancer Research Center RAMSMoscow, Russian Federation.
[Ulyanin, Yurievich Mikhail] Kazan Cancer CenterKazan, Russian Federation.
[Abdrakhmanov, F E] Kazan Cancer CenterKazan, Russian Federation.
[Khasanov, Shamilyevich Rustem] Kazan Cancer CenterKazan, Russian Federation.
RP Malkhasyan, K (reprint author), N. N. Blokhin Russian Cancer Research Center RAMS, Moscow, Russian Federation.
EM karen.malkhasyan@gmail.com
CR Davydov M, Aksel E, 2009, Statistics of the malignant neoplasm in Russia and CIS countries in 2007. J Blokhin RCRC RAMS 20, N3(77)
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Sevankaev A, Lushnikov E, Karyakin O, Mikhailova G, Gorban N, Bashkatov S, Golub E, Shkavrova T, Cepenko V, 2008, Clinical use of the FISH method in early detection of superficial bladder cancer. Oncourology 4:61–65
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Magi-Galluzzi C, Epstein JI, 2004, Urothelial papilloma of the bladder: a review of 34 de novo cases. Am J Surg Pathol 28, 12):1615–1620
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1059
EP 1066
DI 10.1007/s12253-012-9544-6
PG 8
ER
PT J
AU Jeong, HE
Koo, HD
Lee, HS
Bang, BK
Park, HE
Seol, SJ
Lee, YJ
Pyo, SJ
Kim, HD
Lee, JH
Oh, S
AF Jeong, Haeng Eun
Koo, Hoe Dong
Lee, Hyuk Sang
Bang, Bae Ki
Park, Hye Eun
Seol, Soo Ji
Lee, Yong Ji
Pyo, Soo Jung
Kim, Hoon Dong
Lee, Jin Hee
Oh, Sukjoong
TI Aggressive Classical Kaposi’s Sarcoma Mimicking Malignant Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Classical Kaposi’s sarcoma; Human herpesvirus-8; Lymphoma
ID Classical Kaposi’s sarcoma; Human herpesvirus-8; Lymphoma
AB Classical Kaposi’s sarcoma is an unusual multifocal neoplasm of vascular endothelial cell origin, and considered a less malignant, slowly-progressing tumor. Although visceral involvement is occasionally seen in HIV/AIDS patients with KS, tumor dissemination to visceral lymph nodes in classical KS is very rare. A 72-yearold woman without any other relevant past medical history presented with anorexia, weight loss, night sweats, and skin eruptions. As the rapid progression of cytopenias and lymphadenopathy were observed, bone marrow biopsy and imaging were performed. Positron emission tomography showed disseminated lymphadenopathy in the cervical, axillary, mediastinal, inguinal, and abdomino-pelvic nodal areas. Inguinal lymph node biopsy was compatible with KS, positive for CD31, CD34, and human herpesvirus-8 by immunohistochemical stain. We report a case of aggressive classical KS mimicking aggressive malignant lymphoma.
C1 [Jeong, Haeng Eun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Koo, Hoe Dong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Lee, Hyuk Sang] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Bang, Bae Ki] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Park, Hye Eun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Seol, Soo Ji] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Lee, Yong Ji] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
[Pyo, Soo Jung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of PathologySeoul, South Korea.
[Kim, Hoon Dong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of PathologySeoul, South Korea.
[Lee, Jin Hee] University of Ulsan College of Medicine, Asan Medical Center, Department of PathologySeoul, South Korea.
[Oh, Sukjoong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 108 Pyung-Dong, Chongno-Gu, 110-746 Seoul, South Korea.
RP Koo, HD (reprint author), Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal Medicine, 110-746 Seoul, South Korea.
EM dhkoo.smc@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1067
EP 1069
DI 10.1007/s12253-012-9545-5
PG 3
ER
PT J
AU Literati-Nagy, Zs
Tory, K
Literati-Nagy, B
Kolonics, A
Vigh, L
Vigh, L
Mandl, J
Szilvassy, Z
AF Literati-Nagy, Zsuzsanna
Tory, Kalman
Literati-Nagy, Botond
Kolonics, Attila
Vigh, Laszlo
Vigh, Laszlo
Mandl, Jozsef
Szilvassy, Zoltan
TI A Novel Insulin Sensitizer Drug Candidate—BGP-15—Can Prevent Metabolic Side Effects of Atypical Antipsychotics
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Atypical antipsychotic drugs; Side effects; BGP-15; Hydroxylamine derivative; Insulin resistance; Weight gain; Hyperinsulinaemic euglycaemic glucose clamp
ID Atypical antipsychotic drugs; Side effects; BGP-15; Hydroxylamine derivative; Insulin resistance; Weight gain; Hyperinsulinaemic euglycaemic glucose clamp
AB Atypical antipsychotic drugs (AAPD) are widely used to treat severe psychiatric disorders, have well documented metabolic side effects such as disturbances in glucose metabolism, insulin resistance and weight gain. It has been shown that BGP-15, a hydroxylamine derivative with insulin sensitizing activity can prevent AAPD provoked fat accumulation in adipocyte cultures, and insulin resistance in animal experiments and in healthy volunteers. The aim of this study was to compare the preventive effect of BGP-15 with conventional oral antidiabetics on metabolic side effects of AAPDs. We found that BGP-15 that does not belong to either conventional insulin sensitizers or oral antidiabetics, is able to counteract insulin resistance and weight gain provoked by antipsychotic agents in rats while rosiglitazone and metformin were not effective in the applied doses. Our results confirm that BGP-15 is a promising new drug candidate to control the metabolic side effects of atypical antipsychotics. Data indicate that this rat model is suitable to analyze the metabolic side effects of AAPDs and the protective mechanism of BGP-15.
C1 [Literati-Nagy, Zsuzsanna] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Tory, Kalman] N-Gene Research and Development LtdBudapest, Hungary.
[Literati-Nagy, Botond] Drug Research Center LtdBalatonfured, Hungary.
[Kolonics, Attila] N-Gene Research and Development LtdBudapest, Hungary.
[Vigh, Laszlo] Mecsek Pharma Research LtdPecs, Hungary.
[Vigh, Laszlo] Hungarian Academy of Sciences, Biological Research CenterSzeged, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Szilvassy, Zoltan] University of Debrecen, Department of Pharmacology and Pharmacotherapy, 4032 Debrecen, Hungary.
RP Tory, K (reprint author), N-Gene Research and Development Ltd, Budapest, Hungary.
EM trklmn@gmail.com
CR Gardner DM, Baldessarini RJ, Waraich P, 2005, Modern antipsychotic drugs: a critical overview. CMAJ 172:1703–1711
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Literati-Nagy B, Kulcsar E, Literati-Nagy Z, Buday B, Petrfai E, Horvath T, Tory K, Kolonics A, Fleming A, Mandl J, Koranyi L, 2009, Improvement of insulin sensitivity by a novel drug, BGP- 15, in insulin-resistant patients: a proof of concept randomized double-blind clinical trial. Horm Metab Res 41:374–380
Tim Crul, Noemi Toth, Stefano Piotto, Peter Literati-Nagy, Kalman Tory, Pierre Haldimann, Bernadett Kalmar, Linda Greensmith, Zsolt Torok, Gabor Balogh, Imre Gombos, Federica Campana, Simona Concilio, Ferenc Gallyas, Gabor Nagy, Zoltan Berente, Burcin Gungor, Maria Peter, Attila Glatz, Akos Hunya, Zsuzsanna Literati-Nagy, Laszlo Vigh Jr., Femke Hoogstra-Berends, Andre Heeres, Irma Kuipers, Lizette Loen, Jean-Paul Seerden, Deli Zhang, Roelien A M Meijering, Robert H Henning, Bianca JJM Brundel, Harm H Kampinga, Laszlo Koranyi, Zoltan Szilvassy, Jozsef Mandl, Balazs Sumegi, Mark A Febbraio, Ibolya Horvath, Philip L Hooper, Laszlo Vigh, 2012, Hydroximic acid derivatives: pleiotrophic HSP coinducers restoring homeostasis and robustness. Curr. Phar. Des, in press).
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Literati-Nagy B, Peterfai E, Kulcsar E, Literati-Nagy Z, Buday B, Tory K, Mandl J, Sumegi B, Fleming A, Roth J, Koranyi L, 2010, Beneficial effect of the insulin sensitizer, HSP co-inducer, BGP- 15 on olanzapine-induced metabolic disorders. Brain Res Bull 83:340–344
Literati-Nagy Z, Tory K, Literati-Nagy B, Kolonics A, Torok Z, Gombos I, Balogh G, Vigh L Jr, Horvath I, Mandl J, Sumegi B, Hooper PL, Vigh L, 2012, The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics. Cell Stress Chaperon., DOI 10.1007/s12192-012-0327-5
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1071
EP 1076
DI 10.1007/s12253-012-9546-4
PG 6
ER
PT J
AU Yadamsuren, EA
Nagy, Sz
Pajor, L
Lacza,
Bogner, B
AF Yadamsuren, Enkh-Amar
Nagy, Szilvia
Pajor, Laszlo
Lacza, Agnes
Bogner, Barna
TI Characteristics of Advanced- and Non Advanced Sporadic Polypoid Colorectal Adenomas: Correlation to KRAS Mutations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sporadic colorectal adenomas; Villous architecture; KRAS mutation; Adenoma progression
ID Sporadic colorectal adenomas; Villous architecture; KRAS mutation; Adenoma progression
AB The malignant potential of colorectal adenomas highly correlates with their pathological characteristics, such as size, histology and grade of dysplasia. Currently, based on these parameters, adenomas are characterized as "nonadvanced or advanced" and patient surveillance is adjusted accordingly. The aim of this study was to investigate the correlation between the KRAS mutations and characteristics of non-advanced and advanced colorectal adenomas for predicting the risk of increased malignant potential of adenomas that may influence the decision to offer follow-up endoscopic surveillance. We used a mutagenic polymerase chain reaction – restriction fragment length polymorphism method to determine KRAS mutations in 164 colorectal sporadic polypoid adenomas (51 non-advanced-, 113 advanced adenomas) and in 40 early colorectal carcinomas. The method of mutation detection was validated according to recommendation for KRAS mutation testing in colorectal carcinoma of the European Quality Assurance Program. The limit of detection of the assay was 3 % mutated DNA with a good reproducibility. Evaluation of pathological characteristics was performed according to European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis. The morphological parameters of the adenoma such as size, histology, grade of dysplasia are highly correlated with one another: an increasing adenoma size raised the proportion of villous histology and degree of dysplasia (all p<0.0001). KRAS mutations were detected in 31 % of the non-advanced adenomas, in 57.5 % of the advanced adenomas and in 62.5 % of the early carcinomas. Most mutations occurred at codon 12 rather than at codon 13 (72 %, 82 %, 76 % versus 22 %, 17 %, 24 %, respectively). There was no significant difference in association of KRAS mutation with age, gender, location among non-advanced-, and advanced adenomas and early carcinomas. KRAS mutation was found more often in tubulovillous and villous adenomas, whereas wild-type KRAS was observed more frequently in tubular adenomas (P<0.0001) and there was an increased prevalence of KRAS mutations in larger adenomas (P<0.0001). In this study KRAS mutation occurred with the same frequency in adenomas with low-grade (48 %) and high-grade (50 %) dysplasia. KRAS mutation is very strongly associated with a villous architecture and through villous component expansion, KRAS mutations may increase risk of tumor progression in sporadic colorectal polypoid adenomas.
C1 [Yadamsuren, Enkh-Amar] University of Pecs, Department of Pathology, Szigeti str. 12, 7624 Pecs, Hungary.
[Nagy, Szilvia] University of Pecs, Department of Neurology, 7623 Pecs, Hungary.
[Pajor, Laszlo] University of Pecs, Department of Pathology, Szigeti str. 12, 7624 Pecs, Hungary.
[Lacza, Agnes] University of Pecs, Department of Pathology, Szigeti str. 12, 7624 Pecs, Hungary.
[Bogner, Barna] University of Pecs, Department of Pathology, Szigeti str. 12, 7624 Pecs, Hungary.
RP Bogner, B (reprint author), University of Pecs, Department of Pathology, 7624 Pecs, Hungary.
EM bogner.barna@gmail.com
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Van Krieken JHJM, Jung A, Kirchner T et al, 2008, KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance programme. Virchow Arch 453:417–431
Amicarelli G, Adlerstein D, Shehi E, Wang F, Makrigiorgos GM, 2006, Genotype-specific signal generation based on digestion of 3-Way DNA junctions: application to KRAS variation detection. Clin Chem 52(10):1855–1863
Krypuy M, Newnham GM, Thomas DM et al, 2006, High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer. BMC. Cancer 6:295
Brink M, de Goeij AFPM, Weijenberg MP et al, 2003, K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study. Carcinogenesis 24(4):703–710
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Jass JR, Baker K, Zlolec I et al, 2006, Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a’fusion’ pathway to colorectal cancer. Histopathology 49:121–131
Risio M, 2010, The natural history of adenomas. Best Practice & Research Clinical Gastroenterology 24:271–280
Appelman HD, 2008, Con: High-grade dysplasia and villous features should not be part of the routine diagnosis of colorectal adenomas. Am J Gastroenterol 103:1329–1331
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Nusko G, Sachse R, Mansmann U et al, 1997, K-RAS-2 gene mutations as predictors of metachronous colorectal adenomas. Scand J Gastroenterol 32:1035–1041
Wang JY, Wang YH, Jao SW et al, 2006, Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: correlation to activated K-ras oncogene. Oncol Rep 16:1245–1252
O’Brien MJ, Yang S, Mack C et al, 2006, Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol 30:1491–1501
Risio M, Malacarne D, Giaretti W, 2005, KRAS transitions and villous growth in colorectal adenomas. Cell Oncology 27:363–366
Ishii T, Notohara K, Umapathy A et al, 2011, Tubular adenomas with minor villous changes show molecular features characteristic of tubulovillous adenomas. Am J Surg Pathol 35:212–220
Saini SD, Kim HM, Schoenfeld P, 2006, Incidence of advanced adenomas at surveillance colonoscopy in patients with a personal history of colon adenomas: a meta-analysis and systematic review. Gastrointest Endosc 64:614–626
Calistri D, Rengucci C, Seymour I et al, 2005, Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression. J Cell Physiol 204:484–488
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1077
EP 1084
DI 10.1007/s12253-012-9547-3
PG 8
ER
PT J
AU Gravante, G
Ong, LS
West, K
McGregor, A
Maddern, JG
Metcalfe, SM
Lloyd, MD
Dennison, RA
AF Gravante, Gianpiero
Ong, Ling Seok
West, Kevin
McGregor, Angus
Maddern, J Guy
Metcalfe, S Matthew
Lloyd, M David
Dennison, R Ashley
TI Patterns of Histological Changes following Hepatic Electrolytic Ablation in an Ex-Vivo Perfused Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ex-vivo; Liver; Histology; Pathology; Electrolytic ablation
ID Ex-vivo; Liver; Histology; Pathology; Electrolytic ablation
AB Electrolytic ablation (EA) destroys the liver by releasing toxic radicles and producing modifications in the local pH without increasing the tissue temperature. We assessed the histological changes produced by EA using an ex-vivo perfused model. Five porcine livers were harvested, preserved in ice and reperfused for six hours in an extracorporeal circuit using autologous normothermic blood. One hour after reperfusion EA was performed and liver biopsies collected at the end of the experiments. The main necrotic zone consisted of coagulative necrosis, sinusoidal dilatation and haemorrhage with an unusual morphological pattern. The coagulative necrosis and haemorrhage affected mainly the peripheral area of the lobule with relative sparing of the area surrounding the centrilobular vein. Contrasting with this sinusoidal dilatation appeared to be more prominent in the centrilobular area. EA produces patterns of tissue destruction that have not been observed with the more commonly used thermal techniques. Further studies should obtain more information about the influence of adjacent biliary and vascular structures so that appropriate clinical trials can be designed.
C1 [Gravante, Gianpiero] Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, Gwendolen Road, LE5 4PW Leicester, UK.
[Ong, Ling Seok] Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, Gwendolen Road, LE5 4PW Leicester, UK.
[West, Kevin] University Hospitals of Leicester NHS Trust, Department of HistopathologyLeicester, UK.
[McGregor, Angus] University Hospitals of Leicester NHS Trust, Department of HistopathologyLeicester, UK.
[Maddern, J Guy] The Queen Elizabeth Hospital, Department of Surgery, University of AdelaideWoodville, Australia.
[Metcalfe, S Matthew] Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, Gwendolen Road, LE5 4PW Leicester, UK.
[Lloyd, M David] Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, Gwendolen Road, LE5 4PW Leicester, UK.
[Dennison, R Ashley] Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, Gwendolen Road, LE5 4PW Leicester, UK.
RP Gravante, G (reprint author), Leicester General Hospital, Department of Hepatobiliary and Pancreatic Surgery, LE5 4PW Leicester, UK.
EM ggravante@hotmail.com
CR Robertson GS, Wemyss-Holden SA, Dennison AR et al, 1998, Experimental study of electrolysis-induced hepatic necrosis. Br J Surg 85(9):1212–1216
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1085
EP 1089
DI 10.1007/s12253-012-9549-1
PG 5
ER
PT J
AU Terada, T
AF Terada, Tadashi
TI Primary Esophageal Small Cell Carcinoma with Brain Metastasis and with CD56, KIT, and PDGFRA Expressions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231 Shimizu-Ku, 424–8636 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 424–8636 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
CR Miettinen M, Lasota J, 2005, KIT, CD117): a review on expression in normal and neoplastic tissue, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13:205–220
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Dow N, Giblen G, Sobin LH, Miettinen M, 2006, Gastrointestinal stromal tumors: differential diagnosis. Semin Diagn Pathol 23:111–119
Sihto H, Sarlomo-Rikara M, Tynnienen O, Tanner M, Andersson LC, Franssila K, Nupponen NN, Joensuu H, 2005, KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors. J Clin Oncol 23:49–57
Koide N, Saito H, Suzuki A, Sato T, Koiwai K, Nakamura N, Miyagawa S, 2007, Clinicopathologic features and histochemical analuses of proliferative activity and angiogenesis in small cell carcinoma of the esophagus. J Gastroenterol 42:932–938
Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y, 2002, Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746
Terada T, Kawaguchi M, 2005, Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med 271:271–275
Terada T, 2009, Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Oncol 28:29–34
Terada T, 2009, Primary extragastrointestinal stromal tumor of the transverse mesocolon without c-kit mutations but with PDGFRA mutations. Med Oncol 26:233–237
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Terada T, 2009, Primary small cell carcinoma of the mediastinum: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes. Med Oncol 26:247–250
Terada T, 2010, Primary small cell carcinoma of the ureter: a case report involving immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes. Pathology 42:101–102
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Naeem M, Dahiya M, Clark JI, Creech SD, Alkin S, 2002, Analysis of c-kit protein expression in small-cell lung carcinoma and its implications for prognosis. Hum Pathol 33:1182– 1187
Mojica WD, Saxena R, Starostik P, Cheney RT, 2005, CD117+ small cell lung cancer lacks the asp 816 val point mutation in exon 17. Histopathology 47:517–522
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Burger H, Den Bakker MA, Stoter G, Verweij J, Nooter K, 2003, Lack of c-kit exon 11 activating mutations in c-kit/CD117-positive SCLC tumor specimens. Eur J Cancer 39:793–799
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1091
EP 1093
DI 10.1007/s12253-011-9374-y
PG 3
ER
PT J
AU Wang, Ch
Fu, H
Zhao, FG
Wang, J
Shi, Y
AF Wang, Chunmeng
Fu, H
Zhao, Fang Gong
Wang, Jingmei
Shi, Yongquan
TI CT Scan is not Everything in the Evaluation of a Patient with Gastrointestinal Tumors (GIST) Under Imatinib Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Wang, Chunmeng] Fudan University Shanghai Cancer Center, Abdominal Department, 270 Dong’an Road, 200032 Shanghai, China.
[Fu, H] Fudan University Shanghai Cancer Center, Abdominal Department, 270 Dong’an Road, 200032 Shanghai, China.
[Zhao, Fang Gong] Fudan University Shanghai Cancer Center, Abdominal Department, 270 Dong’an Road, 200032 Shanghai, China.
[Wang, Jingmei] Fudan University Shanghai Cancer Center, Department of Pathology, 270 Dong’an Road, 200032 Shanghai, China.
[Shi, Yongquan] Fudan University Shanghai Cancer Center, Abdominal Department, 270 Dong’an Road, 200032 Shanghai, China.
RP Shi, Y (reprint author), Fudan University Shanghai Cancer Center, Abdominal Department, 200032 Shanghai, China.
EM shiyingqiang@yeah.net
CR Stroszczynski C, Jost D, Reichardt P, Chmelik P, Gaffke G, Kretzschmar A et al, 2005, Follow-up of gastrointestinal stromal tumours(GIST, during treatment with imatinib mesylate by abdominal MRI. Eur Radiol 15:2448–2456
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ et al, 2002, Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480
Phongkitkarun S, Phaisanphrukkun C, Jatchavala J, Sirachainan E, 2008, Assessment of gastrointestinal stromal tumors with computed tomography following treatment with imatinib mesylate. World J Gastroenterol 14:892–898
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al, 2000, New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, Johnson MM et al, 2004, CT Evaluation of the response of gastrointestinal stromal tumors after Imatinib Mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 183:1619–1628
Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL et al, 2007, We should desist using RECIST, at Least in GIST. J Clin Oncol 25:1760–1764
Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR et al, 2007, Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759
Jager PL, Gietema JA, van der Graaf WT, 2004, Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET. Nucl Med Commun 25:433–438
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1095
EP 1097
DI 10.1007/s12253-011-9445-0
PG 3
ER
PT J
AU Ozturk, GO
AF Ozturk, Goruroglu Ozlem
TI HLA Alleles in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Ozturk, Goruroglu Ozlem] Cukurova University, Faculty of Medicine, Department of Clinical Biochemistry, Tibbi Biyokimya AD, 01330 Adana, Turkey.
RP Ozturk, GO (reprint author), Cukurova University, Faculty of Medicine, Department of Clinical Biochemistry, 01330 Adana, Turkey.
EM ozlem_goruroglu@yahoo.com
CR Mahmoodi M, Nahvi H, Mahmoudi M, Kasaian A, Mohagheghi MA, Divsalar K, Nahavandian B, Jafari A, Ansarpour B, Moradi B, Aghamohammadi A, Amirzargar A, 2011, HLA-DRB1,-DQA1 and -DQB1 Allele and Haplotype Frequencies in Female Patients with Early Onset Breast Cancer. Pathol Oncol Res [In press]
Gun FD, Ozturk OG, Polat A, Polat G, 2011, HLA class-II allele frequencies in Turkish breast cancer patients. Med Oncol [In press]
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1099
EP 1099
DI 10.1007/s12253-012-9501-4
PG 1
ER
PT J
AU Ostwal, V
Rekhi, B
Noronha, V
Basak, R
Desai, BS
Maheshwari, A
Prabhash, K
AF Ostwal, Vikas
Rekhi, Bharat
Noronha, Vanita
Basak, Ranjan
Desai, B Sangeeta
Maheshwari, Amita
Prabhash, Kumar
TI Primitive Neuroectodermal Tumor of Ovary in a Young Lady, Confirmed with Molecular and Cytogenetic Results—A Rare Case Report with a Diagnostic and Therapeutic Challenge
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Ostwal, Vikas] Tata Memorial Hospital, Department of Medical Oncology, ParelMumbai, India.
[Rekhi, Bharat] Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Division of Molecular Pathology, KhargarNavi Mumbai, India.
[Noronha, Vanita] Tata Memorial Hospital, Department of Medical Oncology, ParelMumbai, India.
[Basak, Ranjan] Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Division of Molecular Pathology, KhargarNavi Mumbai, India.
[Desai, B Sangeeta] Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Division of Molecular Pathology, KhargarNavi Mumbai, India.
[Maheshwari, Amita] Tata Memorial Hospital, Department of Surgical Oncology (Gynaecology), ParelMumbai, India.
[Prabhash, Kumar] Tata Memorial Hospital, Department of Medical Oncology, ParelMumbai, India.
RP Rekhi, B (reprint author), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Division of Molecular Pathology, Navi Mumbai, India.
EM rekhi.bharat@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2012
VL 18
IS 4
BP 1101
EP 1106
DI 10.1007/s12253-012-9503-2
PG 6
ER
PT J
AU Rusz, O
Kahan, Zs
AF Rusz, Orsolya
Kahan, Zsuzsanna
TI Bone Homeostasis and Breast Cancer: Implications for Complex Therapy and the Maintenance of Bone Integrity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast cancer; Bisphosphonates; Denosumab; Bone; Prevention
ID Breast cancer; Bisphosphonates; Denosumab; Bone; Prevention
AB The standard of care in bone metastases is antiresorptive therapy. If present in the bone, tumor cells induce a vicious cycle by stimulating the osteoclasts, which further accelerates tumor progression. The widely-used bisphosphonates or the new therapeutic option, denosumab an inhibitor of the receptor activator of NF-κB ligand (RANKL), interrupt this vicious cycle, inhibit tumor growth, and in clinical practice prevent skeleton-related events. Adjuvant oncological therapy, including chemotherapy and endocrine manipulations (ovarian ablation and tamoxifen in premenopausal, and aromatase inhibitors in postmenopausal women), increases the bone turnover and the risk of fracture. Awareness is essential for the diagnosis and treatment of cancer therapyinduced bone loss, or its prevention with appropriate calcium and vitamin D supplementation. A new possibility has been suggested for the prevention of relapse: the use of bisphosphonates in the adjuvant setting. Three large studies and their meta-analyses indicate that the inhibition of bone remodeling prevents the growth of dormant tumor cells and cancer relapse in the population of postmenopausal patients with a lowestrogen environment in the skeleton. The similar potential of a RANKL inhibitor is currently under evaluation. Since the maintenance of bone integrity is necessary for the prevention of both therapy-related side-effects and progression of the disease, the management of breast cancer at any stage requires a careful consideration of the bone homeostasis.
C1 [Rusz, Orsolya] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM kahan.zsuzsanna@med.u-szeged.hu
CR Van Poznak CH, Temin S, Yee GC et al, 2011, American society of clinical oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 29:1221–1227
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Clemons M, Dranitsaris G, Ooi W, Cole DEC, 2008, A phase II trial evaluating the palliative benefit of second-line oral ibandronate in breast cancer patients with either a skeletal related event, SRE, or progressive bone metastases, BM, despite standard bisphosphonate, BP, therapy. Breast Canc Res Treat 108:79–85
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 1
EP 10
DI 10.1007/s12253-012-9586-9
PG 10
ER
PT J
AU Pan, G
Zhang, X
Ren, J
Lu, J
Li, W
Fu, H
Zhang, Sh
Li, J
AF Pan, Guoqing
Zhang, Xiangling
Ren, Junyu
Lu, Jianbo
Li, Wenliang
Fu, Hongmei
Zhang, Shufang
Li, Jun
TI Semaphorin 5A, an Axon Guidance Molecule, Enhances the Invasion and Metastasis of Human Gastric Cancer through Activation of MMP9
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Semaphorin 5A; Gastric cancer; Invasion and metastasis; MMP9; ErK1/2
ID Semaphorin 5A; Gastric cancer; Invasion and metastasis; MMP9; ErK1/2
AB Semaphorin 5A, a member of semaphorin family, was originally identified as axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, its functional roles and mechanism(s) in invasion and metastasis of gastric cancer remain unclear. By using human gastric caner cell lines Parental SGC7901, SGC7901-siScrambled and SGC7901-siSema 5A, we found that semaphorin 5A significantly promoted the invasive and metastatic abilities of gastric cancer cell in vitro. Semaphorin 5A increased the expression of MMP9 by activating phosphorylated ErK1/2 in gastric cancer cell. Furthermore, MEK inhibitor PD98059 and MMP9 antibody (Ab) significantly inhibited in vitro invasive and metastatic abilities induced by semaphorin 5A. Taken together, the present work revealed a novel function of semaphorin 5A that the existence of semaphorin 5A could promote invasion and metastasis of gastric cancer by regulating MMP9 expression, at least partially, via the MEK/ERKs signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy.
C1 [Pan, Guoqing] The First Affiliated Hospital of Kunming Medical College, Department of PathologyKunming, Yunnan, China.
[Zhang, Xiangling] The First Affiliated Hospital of Kunming Medical College, Department of Blood TransfusionKunming, Yunnan, China.
[Ren, Junyu] The First Affiliated Hospital of Kunming Medical College, Department of SurgeryKunming, Yunnan, China.
[Lu, Jianbo] The First Affiliated Hospital of Kunming Medical College, Department of PathologyKunming, Yunnan, China.
[Li, Wenliang] The First Affiliated Hospital of Kunming Medical College, Department of SurgeryKunming, Yunnan, China.
[Fu, Hongmei] The First Affiliated Hospital of Kunming Medical College, Department of PathologyKunming, Yunnan, China.
[Zhang, Shufang] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central Laboratory, Renmin road #43, 570208 Haikou, Hainan, China.
[Li, Jun] The First Affiliated Hospital of Kunming Medical College, Department of NephrologyKunming, Yunnan, China.
RP Zhang, Sh (reprint author), Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central Laboratory, 570208 Haikou, China.
EM haikuoyinyuan@163.com
CR Parkin DM, Bray F, Ferlay J et al, 2005, Global cancer statistics, 2002. CA Cancer J Clinic 55:74–108
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 11
EP 18
DI 10.1007/s12253-012-9550-8
PG 8
ER
PT J
AU Zhu, Ch
Wang, Q
Xie, J
Shi, J
Zhou, X
Li, D
Xiong, F
Zhang, L
AF Zhu, Chunrong
Wang, Qingcai
Xie, Jing
Shi, Jinfang
Zhou, Xiumin
Li, Dapeng
Xiong, Feng
Zhang, Lu
TI Expression and Significance of RKIP and E-cadherin in Lung Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RKIP; E-cadherin; Lung squamous cell carcinoma; RT-PCR; Western blot
ID RKIP; E-cadherin; Lung squamous cell carcinoma; RT-PCR; Western blot
AB The purpose of this study was to investigate the expression of Raf kinase inhibitor protein (RKIP) and epithelial cadherin (E-cadherin) in lung squamous cell carcinoma tissue and its correlation with the clinical pathology of lung squamous cell carcinoma. RKIP and E-cadherin mRNA (by RT-PCR) and protein (by western blotting) levels were monitored in carcinoma tissues and surrounding normal tissues from 86 lung squamous cell carcinoma cases, and their positive rates were calculated. The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P<0.05). The positive expression rates were significantly lower in those with lymph node metastasis than in those without (P<0.05). The lower the degree of tumor differentiation, the lower the E-cadherin mRNA positive expression rate (P<0.05). The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in patients at advanced (III, IV) stages than in patients at early (I, II) stages (p<0.05); this rate, however, was independent of gender, age, and tumor size (P>0.05). The protein levels of RKIP and E-cadherin were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P<0.05). The levels were significantly lower in patients with lymph node metastasis than in those without it (P<0.05). The lower the degree of tumor differentiation, the lower the protein level of E-cadherin (P< 0.05). Both RKIP and E-cadherin are tumor suppressors, their low expression levels may be associated with initiation, invasion and/or metastasis, as well as with the inhibition of lung squamous cell carcinoma differentiation.
C1 [Zhu, Chunrong] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Wang, Qingcai] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Xie, Jing] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Shi, Jinfang] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Zhou, Xiumin] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Li, Dapeng] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Xiong, Feng] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
[Zhang, Lu] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, No. 188, Shi Zi Rd, 215006 Suzhou, China.
RP Zhu, Ch (reprint author), Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215006 Suzhou, China.
EM zhucr2011@yeah.net
CR Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W, 1999, Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 401:173–7
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 19
EP 26
DI 10.1007/s12253-012-9552-6
PG 8
ER
PT J
AU Engelman, dFBM
Grande, MR
Naves, AM
de Franco, FM
de Paulo Castro Teixeira, V
AF Engelman, de Fatima Brasil Miriam
Grande, Mendes Rogerio
Naves, Andery Marcelo
de Franco, Fabiano Marcello
de Paulo Castro Teixeira, Vicente
TI Integrin-Linked Kinase (ILK) Expression Correlates with Tumor Severity in Clear Cell Renal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Tissue array analysis; Carcinoma; Renal cell; Integrin-linked kinase; Human
ID Immunohistochemistry; Tissue array analysis; Carcinoma; Renal cell; Integrin-linked kinase; Human
AB Integrin-linked kinase (ILK) is an unique intracellular serine/threonine kinase and adapter protein. When dysregulated, it has been associated with increased cell proliferation, anchorage-independent cell growth, evasion of apoptosis, angiogenesis, invasion of surrounding tissues, downregulation of E-cadherin expression, nuclear translocation of β-catenin and metastasis, all features of tumoral malignancy. The objective of the present work was to evaluate the expression of ILK in clear cell renal carcinomas (CCRC) as a possible prognostic indicator. ILK immunoexpression was evaluated in a tissue microarray (TMA) with 45 human CCRCs. In addition, the apoptotic and proliferative indices and the immuno-expression of β-catenin and Ecadherin were also evaluated. E-cadherin expression was significantly decreased in tumors with positive ILK expression in relation to those with negative immunoexpression (p00.011). ILK immunostaining was significantly increased in high-grade in comparison to low-grade CCRCs (p<0.0008). ILK expression was also associated with increased proliferative index (p<0.020), tumor size >7.0 cm (p<0.018) and with renal vein and capsule invasion (p<0.003 and p<0.00). Finally, tumors stage I and II (noninvasive) presented significantly reduced ILK immunoexpression when compared to stage III (locally invasive) (p<0.0028). ILK immunoexpression in CCRC increases with loss of intercellular adhesion, nuclear grading, increased proliferative index and Robson stage. Altogether, our data suggest a possible role for ILK in the progression of CRCC.
C1 [Engelman, de Fatima Brasil Miriam] Universidade do Vale do Sapucai, Faculdade de Ciencias da Saude Dr Jose Antonio Garcia Coutinho, Avenida Alfredo Custodio de Paula 360, 37550000 Pouso Alegre, Minas Gerais, Brazil.
[Grande, Mendes Rogerio] Universidade do Vale do Sapucai, Faculdade de Ciencias da Saude Dr Jose Antonio Garcia Coutinho, Avenida Alfredo Custodio de Paula 360, 37550000 Pouso Alegre, Minas Gerais, Brazil.
[Naves, Andery Marcelo] Sao Paulo University School of Medicine, Department of Pathology, Rua Botucatu Edificio Lemos Torres 1° Andar, 04023-062 Sao Paulo, SP, Brazil.
[de Franco, Fabiano Marcello] Sao Paulo University School of Medicine, Department of Pathology, Rua Botucatu Edificio Lemos Torres 1° Andar, 04023-062 Sao Paulo, SP, Brazil.
[de Paulo Castro Teixeira, Vicente] Sao Paulo University School of Medicine, Department of Pathology, Rua Botucatu Edificio Lemos Torres 1° Andar, 04023-062 Sao Paulo, SP, Brazil.
RP Engelman, dFBM (reprint author), Universidade do Vale do Sapucai, Faculdade de Ciencias da Saude Dr Jose Antonio Garcia Coutinho, 37550000 Pouso Alegre, Brazil.
EM mi.engelman@uol.com.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 27
EP 33
DI 10.1007/s12253-012-9554-4
PG 7
ER
PT J
AU Luo, Y
Tian, L
Ye, F
Yi, M
Chen, X
Huang, Q
AF Luo, Yanli
Tian, Ling
Ye, Feng
Yi, Miaoying
Chen, Xiafang
Huang, Qian
TI The Predictive Role of p16 Deletion, p53 Deletion, and Polysomy 9 and 17 in Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic ductal adenocarcinoma; Prognosis; p16; p53; Deletion; Polysomy
ID Pancreatic ductal adenocarcinoma; Prognosis; p16; p53; Deletion; Polysomy
AB In this study, we investigated p53 and p16 deletions, and chromosome 9 and 17 amplifications in pancreatic ductal adenocarcinoma (PDAC), and further analyzed their associations with clinical characteristics and prognosis of PDAC. A total of 32 PDAC and 23 peritumoral tissues were collected. Molecular abnormalities of CEP9/p16 and CEP17/p53 were detected using Fluorescence in situ hybridization (FISH). Deletions of p16 and p53 were detected in 50 % and 65.7 % of PDAC, respectively. Polysomy 9 and 17 were identified in 75 % and 71.8 % of PDAC, respectively. No p16 and p53 deletion, polysomy 9 and 17 were identified in peritumoral tissues. We also observed significant correlations of p16 deletion, polysomy 9 and 17 with shorter survival of PDAC. P16 deletion, polysomy 9 and 17 are predictive markers for poor prognosis of PDAC patients, but p53 deletion is not associated with the clinical characteristics and prognosis of PDAC.
C1 [Luo, Yanli] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
[Tian, Ling] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
[Ye, Feng] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
[Yi, Miaoying] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
[Chen, Xiafang] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
[Huang, Qian] Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 85 Wujin Road, 200080 Shanghai, China.
RP Huang, Q (reprint author), Shanghai Jiaotong University, First People’s Hospital, Experimental Research Center, 200080 Shanghai, China.
EM qhuang2012@yahoo.com
CR Spratlin JL, Mulder KE, 2011, Looking to the future: biomarkers in the management of pancreatic adenocarcinoma. Int J Mol Sci 12:5895–5907
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 35
EP 40
DI 10.1007/s12253-012-9555-3
PG 6
ER
PT J
AU Boissiere-Michot, F
Denouel, A
Boulle, N
Guillaume, C
Orsetti, B
Lopez-Crapez, E
Chateau, MCh
Bibeau, F
AF Boissiere-Michot, Florence
Denouel, Amelie
Boulle, Nathalie
Guillaume, Carole
Orsetti, Beatrice
Lopez-Crapez, Evelyne
Chateau, Marie-Christine
Bibeau, Frederic
TI The Non-Crosslinking Fixative RCL2®-CS100 is Compatible with Both Pathology Diagnosis and Molecular Analyses
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Fixative; Formalin substitute; Nucleic acids; Morphology
ID Fixative; Formalin substitute; Nucleic acids; Morphology
AB Formalin is the key agent for tissue fixation and pathological diagnosis. However, it poorly preserves nucleic acids and this can impair molecular studies. An alternative to formalin would be a fixative which can allow both morphologic and molecular analyses. To assess the suitability of such a fixative, breast (n011) and colon (n012) tumor samples were fixed in the non cross-linking RCL2®- CS100 fixative and compared to paired formalin-fixed and to frozen samples, the current standards for histology and molecular analyses, respectively. Sections from RCL2®- CS100-fixed samples showed good preservation of cellular and architectural morphology, suitable for routine diagnosis. Although some antibodies required change in the immunohistochemical procedures, quality of the immunohistochemical staining was comparable to that obtained after formalin fixation. HER2 chromogenic in situ hybridization was also successfully performed. High quality DNA could be isolated from RCL2®-CS100-fixed cancer tissues as evidenced by successful amplification of large DNA fragment, CGH array, KRAS and microsatellites genotyping. The quality of RNA from RCL2®-CS100-fixed samples was slightly decreased in comparison to that of RNA isolated from frozen samples, as evidenced by a decreased RNA integrity number but remained exploitable for molecular assays. Our results support the use of the RCL2®-CS100 fixative for histological diagnosis and recovery of high-quality nucleic acids for molecular applications. However, specific procedures for tissue handing and processing, essential to provide high-quality specimens, could limit its use to small target lesions which cannot be frozen without impairing their pathological evaluation.
C1 [Boissiere-Michot, Florence] Val d’Aurelle Cancer Institute, Department of Pathology, 34 298 Montpellier, France.
[Denouel, Amelie] Val d’Aurelle Cancer Institute, Department of Pathology, 34 298 Montpellier, France.
[Boulle, Nathalie] Arnaud de Villeneuve Hospital, Department of Cellular Biology and Hormonology, 34 090 Montpellier, France.
[Guillaume, Carole] Val d’Aurelle Cancer Institute, INSERM U896, 34 298 Montpellier, France.
[Orsetti, Beatrice] Val d’Aurelle Cancer Institute, INSERM U896, 34 298 Montpellier, France.
[Lopez-Crapez, Evelyne] Val d’Aurelle Cancer Institute, Department of Biology, 34 298 Montpellier, France.
[Chateau, Marie-Christine] Val d’Aurelle Cancer Institute, Department of Pathology, 34 298 Montpellier, France.
[Bibeau, Frederic] Val d’Aurelle Cancer Institute, Department of Pathology, 34 298 Montpellier, France.
RP Boissiere-Michot, F (reprint author), Val d’Aurelle Cancer Institute, Department of Pathology, 34 298 Montpellier, France.
EM Florence.Boissiere@montpellier.unicancer.fr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 41
EP 53
DI 10.1007/s12253-012-9556-2
PG 13
ER
PT J
AU Juasook, A
Boonmars, Th
Wu, Z
Loilome, W
Veteewuthacharn, K
Namwat, N
Sudsarn, P
Wonkchalee, O
Sriraj, P
Aukkanimart, R
AF Juasook, Amornrat
Boonmars, Thidarut
Wu, Zhiliang
Loilome, Watcharin
Veteewuthacharn, Kulathida
Namwat, Nissana
Sudsarn, Pakkayanee
Wonkchalee, Orasa
Sriraj, Pranee
Aukkanimart, Ratchadawan
TI Immunosuppressive Prednisolone Enhances Early Cholangiocarcinoma in Syrian Hamsters with Liver Fluke Infection and Administration of N-nitrosodimethylamine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liver fluke; Cholangiocarcinogenesis; Immunosuppressed; Chronic inflammation; Histopathology
ID Liver fluke; Cholangiocarcinogenesis; Immunosuppressed; Chronic inflammation; Histopathology
AB Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumormicroenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation.
C1 [Juasook, Amornrat] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Boonmars, Thidarut] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Wu, Zhiliang] Gifu University, Graduate School of Medicine, Department of Parasitology, Yanagido1-1, 501-1194 Gifu, Japan.
[Loilome, Watcharin] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Veteewuthacharn, Kulathida] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Namwat, Nissana] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Sudsarn, Pakkayanee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Wonkchalee, Orasa] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Sriraj, Pranee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Aukkanimart, Ratchadawan] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
RP Boonmars, Th (reprint author), Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
EM boonmars@yahoo.com;bthida@kku.ac.th
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 55
EP 62
DI 10.1007/s12253-012-9557-1
PG 8
ER
PT J
AU Patonai, A
Erdelyi-Belle, B
Korompay, A
Somoracz,
Torzsok, P
Kovalszky, I
Barbai, T
Raso, E
Lotz, G
Schaff, Zs
Kiss, A
AF Patonai, Attila
Erdelyi-Belle, Boglarka
Korompay, Anna
Somoracz, Aron
Torzsok, Peter
Kovalszky, Ilona
Barbai, Tamas
Raso, Erzsebet
Lotz, Gabor
Schaff, Zsuzsa
Kiss, Andras
TI Molecular Characteristics of Fibrolamellar Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Fibrolamellar hepatocellular carcinoma; Hepatocellular carcinoma; Cholangiocellular carcinoma; Epidermal growth factor receptor; K-RAS mutation
ID Fibrolamellar hepatocellular carcinoma; Hepatocellular carcinoma; Cholangiocellular carcinoma; Epidermal growth factor receptor; K-RAS mutation
AB Fibrolamellar hepatocellular carcinoma (FLC) occurs in non-cirrhotic liver and the etiopathogenesis is still obscure. Both hepatocellular and cholangiocellular markers are expressed in the tumor, however, molecular alterations and altered pathways playing role in the tumor pathogenesis are not clearly identified. The purpose of the present study was to compare the expression level of EGFR, syndecan-1 and ßcatenin in FLC, conventional hepatocellular carcinoma (cHCC) and cholangiocellular carcinoma (CCC) and to investigate the possibility ofmutation both in EGFR and K-RAS. Eight FLCs were compared with 7 cHCCs, 7 CCCs and 5 normal liver samples. Cytokeratins 7, 8, 18, 19, HepPar1 (HSA), EGFR, syndecan-1 (CD138) and ß-catenin were detected by immunohistochemistry. In addition EGFR, ß-catenin and syndecan-1 were evaluated by digital morphometry and K-RAS, EGFR mutations in FLC cases using paraffin-embedded samples. All FLCs were positive for HepPar1 (HSA) and cytokeratins 7, 8, 18, but negative for cytokeratin 19 by immunohistochemistry. EGFR was significantly overexpressed in all three tumor types, being highest in FLCs (p<0,0001). EGFR, K-RAS mutation analyses revealed no mutations in exons studied in FLCs. Our findings proved that expression of EGFR is higher in FLC than in other types of primary malignant hepatic tumors and no KRAS mutation can be detected, so FLC is a good candidate for anti-EGFR treatment.
C1 [Patonai, Attila] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Erdelyi-Belle, Boglarka] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Korompay, Anna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Somoracz, Aron] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Torzsok, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Barbai, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM schaff.zsuzsa@med.semmelweis-univ.hu
CR Abdul-Al HM, Wang G, Makhlouf HR, Goodman ZD, 2010, Fibrolamellar hepatocellular carcinoma: An immunohistochemical comparison with conventional hepatocellular carcinoma. Int J Surg Pathol 18:313–318
Kannangai R, Vivekanandan P, Martinez-Murillo F, Choti M, TorbensonM, 2007, Fibrolamellar carcinomas show overexpression of genes in the RAS, MAPK, PIK3, and xenobiotic degradation pathways. Hum Pathol 38:639–644
Liu S, Chan KW, Wang B, Qiao L, 2009, Fibrolamellar hepatocellular carcinoma. Am J Gastroenterol 104:2617–2624
Torbenson M, 2007, Review of the clinicopathologic features of fibrolamellar carcinoma. Adv Anat Pathol 14:217–223
Ward SC, Huang J, Tickoo SK, Thung SN, Ladanyi M, Klimstra DS, 2010, Fibrolamellar carcinoma of the liver exhibits immunohistochemical evidence of both hepatocyte and bile duct differentiation. Mod Pathol 23:1180–1190
Patonai A, Erdelyi-Belle B, Korompay A, Somoracz A, Straub BK, Schirmacher P, Kovalszky I, Lotz G, Kiss A, Schaff Z, 2011, Claudins and tricellulin in fibrolamellar hepatocellular carcinoma. Virchows Arch 458:679–688
Kakar S, Chen X, Ho C, Burgart LJ, Sahai V, Dachrut S, Yabes A, Jain D, Ferrell LD, 2009, Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization. Hum Pathol 22:134–141
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Vivekanandan P, Daniel H, Yeh MM, Torbenson M, 2010, Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas. Mod Pathol 23:790–798
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 63
EP 70
DI 10.1007/s12253-012-9558-0
PG 8
ER
PT J
AU Bezic, J
Samija-Projic, I
Projic, P
Ljubkovic, J
Tomas-Zekic, S
Marinovic-Guic, M
Tomic, S
AF Bezic, Josko
Samija-Projic, Ivana
Projic, Petar
Ljubkovic, Jelena
Tomas-Zekic, Sandra
Marinovic-Guic, Maja
Tomic, Snjezana
TI Near-Diploid Hyperploidy in Early Breast Cancer (T1a,b) is Associated with Higher Risk of Lymph Node Involvement
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Early breast cancer; Nodal metastases; DNA flow cytometry; DNA index
ID Early breast cancer; Nodal metastases; DNA flow cytometry; DNA index
AB Due to the worldwide implementation of the mammographic screening program early breast cancer (T1a,b) has become more prevalent form of breast cancer. Although T1a,b breast cancers are generally associated with excellent prognosis, some of them, particularly those with lymph node involvement, has unfavourable outcome. Searching for additional prognostic factors, we investigated DNA content of 163 T1a,b cancers measured by DNA flow cytometry, and correlated it with regional lymph node status. T1a,b cancers were divided into four ploidy classes based on their DNA index (DI): hypodiploid (DI<0.95), diploid (DI 0.95–1.05), low-hyperploid (DI 1.06–1.3), and highhyperploid (DI>1.3). Diploid T1a,b cancers were associated with negative lymph node status (p<0.003). Among aneuploid cancers only low-hyperploid tumors were associated with positive lymph node status (p<0.03). The histopathological features of low-hyperploid group of T1a,b cancers did not differ from the other three ploidy groups of cancers, except for lower S-phase fraction of tumor cells in lowhyperploid group compared to high-hyperploid group (p<0.01). Our data showed that near-diploid hyperploid T1a,b cancers are associated with higher risk of lymph node involvement despite similar clinicopathological features shared with other ploidy classes of T1a,b tumors.
C1 [Bezic, Josko] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
[Samija-Projic, Ivana] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
[Projic, Petar] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
[Ljubkovic, Jelena] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
[Tomas-Zekic, Sandra] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
[Marinovic-Guic, Maja] University of Split, School of MedicineSplit, Croatia.
[Tomic, Snjezana] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21 000 Split, Croatia.
RP Bezic, J (reprint author), University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, 21 000 Split, Croatia.
EM jbezic@mefst.hr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 71
EP 77
DI 10.1007/s12253-012-9559-z
PG 7
ER
PT J
AU Zhang, Y
Tan, YF
Jiang, Ch
Zhang, K
Zha, TZ
Zhang, M
AF Zhang, Yun
Tan, Yong-Fei
Jiang, Chao
Zhang, Kai
Zha, Tian-Zhou
Zhang, Miao
TI High ADAM8 Expression is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ADAM8; Hepatocellular carcinoma; Biomarker; Prognosis; Immunohistochemical analysis
ID ADAM8; Hepatocellular carcinoma; Biomarker; Prognosis; Immunohistochemical analysis
AB In this study,we investigated the ADAM8 expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features,including the survival of patients with HCC. Furthermore,we examined the biological processes regulated by ADAM8 during the development of using HepG2 cell line as a model system. We used immunohistochemistry to compare ADAM8 protein expression in HCC and normal liver tissues and further analyze the ADAM8 protein expression in clinicopathologically characterized 105 HCC cases.We stably knocked down the endogenous expression level of ADAM8 in HepG2 cells with specific shRNA expressing lentiviral vector. Following the successful establishment of stable cells,we examined in vitro cell growth by MTT assay,anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition,we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Protein expression level of ADAM8 was markedly higher in HCC tissues than that in the normal liver tissues (P<0.0058).In addition,high expression of ADAM8 protein was positively correlated with serum AFP elevation,tumor size,histological differentiation,tumor recurrence,tumor metastasis,and tumor stage. Patients with higher ADAM8 expression showed a significantly shorter overall survival time than patients with low ADAM8 expression. Multivariate analysis suggested that ADAM8 expression might be an independent prognostic indicator (p00.016) for the survival of patients with HCC. ADAM8-specific shRNA (shADAM8) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells,the shADAM8 cells exhibited significantly reduced in vitro cell growth,anchorageindependent growth,cell migration and invasion (p<0.05).In vivo,the xenograft transplants from shADAM8 cells gave rise to much smaller tumors as compared to those from shCtrl cells. High ADAM8 expression is associated with poor overall survival in patients with HCC. Down-regulation of ADAM8 inhibits the growth,anchorage-independent growth, migration and invasion of HepG2 cells. ADAM8 may be a potential target of antiangiogenic therapy for HCC.
C1 [Zhang, Yun] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
[Tan, Yong-Fei] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
[Jiang, Chao] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
[Zhang, Kai] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
[Zha, Tian-Zhou] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
[Zhang, Miao] Yixing People’s Hospital, Department of General Surgery, No. 75, Tongzhen Guan Rd, 214200 Yixing, China.
RP Tan, YF (reprint author), Yixing People’s Hospital, Department of General Surgery, 214200 Yixing, China.
EM yongfeitan@yahoo.com.cn
CR Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, TaylorRobinson SD, 2009, Hepatocellular carcinoma:current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol 3:353–367
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Koorey D, 2007, Hepatocellular carcinoma:prevention, detection and treatment in the real world. Intern Med J 37:513–515
Pleguezuelo M, Marelli L, Misseri M, Germani G, Calvaruso V, Xiruochakis E et al, 2008, TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 8:1623–1641
Yoshiyama K, Higuchi Y, Kataoka M, Matsuura K, Yamamoto S, 1997, CD156(human ADAM8):expression, primary amino acid sequence, and gene location. Genomics 41(1):56–62
Yamamoto S, Higuchi Y, Yoshiyama K et al, 1999, ADAM family proteins in the immune system. Immunol Today 20(6):278–284
Schlomann U, Wildeboer D, Webster A et al, 2002, The metalloprotease disintegrin ADAM8. Processing by autocatalysis is required for proteolytic activity and cell adhesion. Biol Chem 277(50):48210–48219
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Fourie AM, Coles F, Moreno V, Karlsson L, 2003, Catalytic activity of ADAM8, ADAM15, and MDC-L, ADAM28, on synthetic peptide substrates and in ectodomain cleavage of CD23. J Biol Chem 278(33):30469–30477
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Valkovskaya NV, 2008, Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines. Exp Oncol 30(2):129–132
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Tuck AB, O'Malley FP, Singhal H et al, 1998, Osteopontin expression in a group of lymph node negative breast cancer patients. Int J Cancer 79:502–508
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 79
EP 88
DI 10.1007/s12253-012-9560-6
PG 10
ER
PT J
AU Masood, N
Kayani, AM
AF Masood, Nosheen
Kayani, Akhtar Mahmood
TI Expression Patterns of Carcinogen Detoxifying Genes (CYP1A1, GSTP1 & GSTT1) in HNC Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; GSTP1; CYP1A1; GSTT1
ID Immunohistochemistry; GSTP1; CYP1A1; GSTT1
AB Carcinogen detoxifying genes may be involved in pathogenesis of head and neck cancer (HNC). CYP1A1 is phase I enzyme that converts carcinogens into water soluble compounds which are easily excreted from body. GSTs constitute phase II detoxification enzymes that recognize these highly electrophilic compounds and detoxify them. Abnormal expression of these genes can potentially lead to cancer initiation. In present study, we analyzed protein expression of these genes in a total of 192 HNC patients and noncancerous healthy control serum samples screened for GSTs specific activity by ELISA. Furthermore, expression of these molecules was also determined in 49 HNC tissues/ adjacent control tissue by immunohistochemistry with specific antibodies. Mean serum GSTs specific activity was found to be 7.7 (+11.5)U/L in HNC patients and 11.4 (+7.5)U/L in controls. Significant decrease (P<0.05) in GSTs specific activity was observed in HNC patients compared with controls (P<0.001). Data for immunohistochemistry showed that CYP1A1 and GSTT1 was down expressed whereas GSTP1 was over expressed in HNC tissues compared with adjacent normal control tissues. Results of immunohistochemistry revealed 63 % HNC tissues had weak, 27 % moderate and 10 % strong staining for CYP1A1. For GSTT1, 27 % HNC tissues had no staining, 49 % weak staining, 16 % moderate and 8 % strong staining. Similarly for GSTP1, percentages for weak, moderate and strong staining were 6 %, 12 % and 82 % respectively. These reduced proteins observed in cancer patients highlight a potential breach on DNA repair mechanism when compared with control. Thus altered expression of these detoxifying molecules may collectively contribute to HNC development in Pakistani population.
C1 [Masood, Nosheen] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Kayani, Akhtar Mahmood] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
RP Masood, N (reprint author), COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics Lab, Islamabad, Pakistan.
EM nosheenmasood@hotmail.com
CR Bhurgri Y, 2005, Cancer of the oral cavity- trends in Karachi south, 1995–2002). Asian Pac J Cancer Prev 6(1):22–26
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Hanif M, Zaidi P, Kamal S, Hameed A, 2009, Institution based cancer incidence in a local population in Pakistan: nine year data analysis. Asian Pac J Cancer Prev 10(2):227–230
Guengerich FP, Simada T, 1991, Oxidation of toxic and carcinogenic chemicals by human cytochrome P 450 enzymes. Chem Res Toxicol 4:341–407
Masood N, Kayani MA, 2011, Mutational analysis of xenobiotic metabolizing genes, CYP1A1 and GSTP1, in sporadic head and neck cancer patients. Genet Mol Biol 34(4):533–538
Masood N, Kayani MA, Malik FA, Ishrat M, Baig RM, Faryal R, 2011, Genetic variations in carcinogen metabolizing genes associated with oral cancer in Pakistani population. Asian Pac J Cancer Prev 12:491–495
Masood N, Malik FA, Ishrat M, Baig RM, Kayani MA, 2011, A novel CYP1A1 gene polymorphism and the risk of head and neck cancer in Pakistani population. Afr J Biotechnol 10(27):5273–5280
Masood N, Ishrat M, Malik FA, Baig RM, Kayani MA, 2010, Association of GSTM1 and GSTT1 gene deletions with risk of head and neck cancer in Pakistan: a case control study. Asian Pac J Cancer Prev 11:881–885
Masood N, Malik FA, Kayani MA, 2011, Expression of xenobiotic metabolizing genes in head and neck cancer tissues. Asian Pac J Cancer Prev 12(2):377–382
Farin FM, Bigler LG, Oda D, McDougall JK, Omiecinski CJ, 1995, Expression of cytochrome P450 and microsomal exposide hydrolase in cervical and oral epithelial cells immortalized by human papillomavirus type 16 E6/E7 genes. Carcinogenesis 16:1670
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Patel BP, Raval GN, Rawal RM, Patel JB, Sainger RN, Patel MM, Shah MH, Patel DD, Patel PS, 2002, Serum glutathione-Stransferase and glutathione reductase activity in head and neck cancer patients. Neoplasma 49(4):260–266
Ferruzzi E, Franceschini R, Cazzolato G, Geroni C, Fowst C, Pastorino U, Tradati N, Tursi J, Dittadi R, Gion M, 2003, Blood glutathione as a surrogate marker of cancer tissue glutathione Stransferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck. Eur J Cancer 39(7):1019– 1029
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 89
EP 94
DI 10.1007/s12253-012-9563-3
PG 6
ER
PT J
AU Cserni, G
Bori, R
Maraz, R
Leidenius, HKM
Meretoja, JT
Heikkila, SP
Regitnig, P
Luschin-Ebengreuth, G
Zgajnar, J
Perhavec, A
Gazic, B
Lazar, Gy
Takacs, T
Voros, A
Audisio, AR
AF Cserni, Gabor
Bori, Rita
Maraz, Robert
Leidenius, H K Marjut
Meretoja, J Tuomo
Heikkila, S Paivi
Regitnig, Peter
Luschin-Ebengreuth, Gero
Zgajnar, Janez
Perhavec, Andraz
Gazic, Barbara
Lazar, Gyorgy
Takacs, Tibor
Voros, Andras
Audisio, A Riccardo
TI Multi-Institutional Comparison of Non-sentinel Lymph Node Predictive Tools in Breast Cancer Patients with High Predicted Risk of Further Axillary Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sentinel lymph node; Non-sentinel lymph node; Breast cancer; Nomogram; High risk; Axillary lymph node dissection
ID Sentinel lymph node; Non-sentinel lymph node; Breast cancer; Nomogram; High risk; Axillary lymph node dissection
AB Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.
C1 [Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 2, 6720 Szeged, Hungary.
[Bori, Rita] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Maraz, Robert] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Leidenius, H K Marjut] Helsinki University Central Hospital, Breast Surgery Unit, 00029 Helsinki, Finland.
[Meretoja, J Tuomo] Helsinki University Central Hospital, Breast Surgery Unit, 00029 Helsinki, Finland.
[Heikkila, S Paivi] Helsinki University Central Hospital, Department of Pathology, 00029 Helsinki, Finland.
[Regitnig, Peter] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, 8036 Graz, Austria.
[Luschin-Ebengreuth, Gero] Medical University of Graz, Department of Obstetrics and Gynecology, Auenbruggerplatz 25, 8036 Graz, Austria.
[Zgajnar, Janez] Institute of Oncology, Department of Surgical Oncology, Zaloska c. 2, 1105 Ljubljana, Slovenia.
[Perhavec, Andraz] Institute of Oncology, Department of Surgical Oncology, Zaloska c. 2, 1105 Ljubljana, Slovenia.
[Gazic, Barbara] Institute of Oncology, Department of Pathology, Zaloska c. 2, 1105 Ljubljana, Slovenia.
[Lazar, Gyorgy] University of Szeged, Department of Surgery, Pecsi u 6, 6720 Szeged, Hungary.
[Takacs, Tibor] University of Szeged, Department of Surgery, Pecsi u 6, 6720 Szeged, Hungary.
[Voros, Andras] University of Szeged, Department of Pathology, Allomas u. 2, 6720 Szeged, Hungary.
[Audisio, A Riccardo] St Helens Teaching Hospital, Department of Surgery, Marshalls Cross Road, WA93DA St Helens, UK.
RP Cserni, G (reprint author), University of Szeged, Department of Pathology, 6720 Szeged, Hungary.
EM cserni@freemail.hu
CR Lyman GH, Giuliano AE, Somerfield MR et al, 2005, American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 95
EP 101
DI 10.1007/s12253-012-9553-5
PG 7
ER
PT J
AU Pagni, F
Zannella, S
Ronchi, S
Garanzini, C
Leone, EB
AF Pagni, Fabio
Zannella, Stefano
Ronchi, Susanna
Garanzini, Cristina
Leone, Eugenio Biagio
TI HER2 Status of Gastric Carcinoma and Corresponding Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Metastasis; HER2; IHC; HER2 status scoring system
ID Gastric cancer; Metastasis; HER2; IHC; HER2 status scoring system
AB Our goal is to verify HER2 status variability between primary tumor and metastatic site. Our second intention is to identify the most reliable criteria for pathological HER2 status assessment in gastric cancer node metastases since, at present, there is not a validated standard. 3 independent pathologists evaluated HER2 immunohistochemical and gene status (for IHC 2+ cases) in 34 gastric carcinoma metastatic lymph nodes and in their corresponding primary tumors. For primary gastric cancers, we followed the current HER2 assessment guidelines and for nodal metastases, we applied two immunohistochemical scoring systems with different cut-offs. The immunohistochemical inter-pathologists mean agreement was 71.4 % (κ00.45); a final score for each case was defined after collegial revision. By applying the two immunohistochemical criteria, we found 2 discordant cases, which can imply different pathological management.Moreover, a significantly different HER2 status between lymph node metastasis and primary tumor was obtained in 4 cases (concordance ratio 87.5 %). None of the patients would have undergone a different therapeutic pathway despite the scoring method applied. On the other hand we also detected a subset of patients who could have their therapeutic management changed, according to the differences between HER2 status in lymph nodes metastases and primary tumor.
C1 [Pagni, Fabio] Desio Hospital, Department of PathologyDesio, Italy.
[Zannella, Stefano] Desio Hospital, Department of PathologyDesio, Italy.
[Ronchi, Susanna] Desio Hospital, Department of PathologyDesio, Italy.
[Garanzini, Cristina] Desio Hospital, Department of PathologyDesio, Italy.
[Leone, Eugenio Biagio] Desio Hospital, Department of PathologyDesio, Italy.
RP Pagni, F (reprint author), Desio Hospital, Department of Pathology, Desio, Italy.
EM petala.83@tiscali.it
CR Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK, 2010, Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer, ToGA): a phase III, openlabel, randomised controlled trial. Lancet 376:687–97
Hoffmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, Ochiai A, Ruschoff J, Henkel T, 2008, Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805
Ruschoff J, Dietel M, Baretton G, Arbogast S, Walch A, Monges G, Chenard MP, Penault-Llorca F, Nagelmeier I, Schlake W, Hofler H, Kreipe HH, 2010, HER2 diagnostics in gastric cancer: guideline validation and development of standardized immunohistochemical testing. Virchows Arch 457:299–307
Wolff AC, Hammond EH M, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, 2007, American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for Human Epidermal Growth Factor Receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18–43
Albarello L, Pecciarini L, Doglioni C, 2011, HER2 Testing in gastric cancer. Adv Anat Pathol 18:53–59
Bozzetti C, Negri FV, Lagrasta CA, Crafa P, Bassano C, Tamagnini I, Gardini G, Nizzoli R, Leonardi F, Gasparro D, Camisa R, Cavalli S, Silini EM, Ardizzoni A, 2011, Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer 104:1372–1376
Nassar A, Cohen C, Agersborg SS, Zhou W, Lynch KA, Albitar M, Barker EA, Vanderbilt BL, Thompson J, Heyman ER, Lange H, Olson A, Siddiqui MT, 2001, Trainable Immunohistochemical HER/neu Image Analysis. A multisite performance study using 260 breast tissue specimen. Arch Pathol Lab Med 135:896–902
Marx AH, Tharun L, Muth J, Dancau AM, Simon R, Yekebas E, Kaifi JT, Mirlacher M, Brummendorf TH, Bokemeyer C, Izbicki JR, Sauter G, 2009, HER-2 amplification is highly homogeneous in gastric cancer. Hum Pathol 40:769–777
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 103
EP 109
DI 10.1007/s12253-012-9564-2
PG 7
ER
PT J
AU Tavares, A
Gandra, A
Viveiros, F
Cidade, C
Maciel, J
AF Tavares, Amelia
Gandra, Antonio
Viveiros, Fernando
Cidade, Cassilda
Maciel, Jorge
TI Analysis of Clinicopathologic Characteristics and Prognosis of Gastric Cancer in Young and Older Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE Cancer gastric; Prognostic; Age
ID Cancer gastric; Prognostic; Age
AB Background: The worldwide incidence of gastric cancer is gradually declining, however it remains the fourth highest in cancer incidence and the second leading cause of cancer death. Gastric cancer in young people is a disturbing problem and the routine screening does not include people less than 35 years. The clinicopathological features of gastric carcinoma are said to differ between young and elderly patients and it is thought that the prognosis of this disease is worse for younger patients. It is also suggested that the diagnosis is usually made later or have a more aggressive behaviour. Although, others report that tumor staging and prognosis for young patients is similar to older patients and depends on whether the patients undergo a curative resection. All these data need more investigation and studies. Although Portugal has a high incidence of gastric cancer, no studies have yet been performed comparing the clinicopathologic features and prognosis of young and elderly patients with gastric cancer. Aims: This study intend to assess whether the clinicopathological features and prognosis of gastric cancer in young patients (YGC) is similar to older ones (OGC). Methods: Between 2000 and 2005, 406 patients with histological diagnosis of primary gastric cancer, treated in the Departments of Surgery and Oncology at the Centro Hospitalar of Vila Nova de Gaia / Espinho, were regularly followed at least for five years after surgery. These were reviewed retrospectively. Several variables were analyzed in young patients and compared with the elder ones. We used the chi-square and Fisher to evaluate the statistical association between categorical variables and t-test for numeric variables. Survival was estimated by the Kaplan- Meier method and used the log-rank test to assess differences in survival among different subgroups of patients. The criteria for statistical significance was p<0.05. Data analysis was performed using the SPSS 18. Results and Conclusions: With regard to resectability, 78 % of the tumors were resected in the group of younger patients, the surgery more frequently achieved was total gastrectomy with anastomosis in Y of Roux. In the elder group, about 62 % of the tumors were resected and BII gastrectomy was the most frequent surgery. The diffuse adenocarcinoma was the most frequent histological type in younger patients, whereas in older patients was intestinal adenocarcinoma. With regard to the stage in the first group there was a predominance of stages: IA and IV (26.1 %) in the second: IV (25.8 %). The survival for stage III e IV was significantly worst in YGC compared with OGC.
C1 [Tavares, Amelia] Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia, Portugal.
[Gandra, Antonio] Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia, Portugal.
[Viveiros, Fernando] Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia, Portugal.
[Cidade, Cassilda] Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia, Portugal.
[Maciel, Jorge] Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia, Portugal.
RP Tavares, A (reprint author), Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
EM ameliassbtavares@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 111
EP 117
DI 10.1007/s12253-012-9530-z
PG 7
ER
PT J
AU Rubovszky, G
Nagy, T
Godeny, M
Szasz, A
Lang, I
AF Rubovszky, Gabor
Nagy, Tunde
Godeny, Maria
Szasz, Andras
Lang, Istvan
TI Successful Treatment of Solitary Bone Metastasis of Non-Small Cell Lung Cancer with Bevacizumab and Hyperthermia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE Solitary bone metastases; Lung cancer; Hyperthermia; Bevacizumab
ID Solitary bone metastases; Lung cancer; Hyperthermia; Bevacizumab
AB Non-small cell lung cancer (NSCLC) represents 85 % of all malignant lung cancers. In metastatic disease the principle goal of palliative therapy is to prolong survival with least toxicity and best patients’ quality of life. Bevacizumab (BEV) has been approved as first line treatment in combination with platinum based chemotherapy and maintenance therapy in NSCLC. BEV can be added safely to several chemotherapeutic agents, however there is no data on coadministration with thermotherapy. Even in localized disease no robust evidence exists about the beneficial effect of loco-regional thermotherapy on overall survival, but it might be used successfully in symptom palliation. In this article a successful co-administration of BEV and hyperthermia is reported in a patient with monolocalized bone metastasis from previously operated NSCLC. This case suggests that electrohyperthermia can probably be incorporated in palliative therapy added not only to radiotherapy or chemotherapy but also to anti-angiogenic BEV treatment.
C1 [Rubovszky, Gabor] National Institute of OncologyBudapest, Hungary.
[Nagy, Tunde] National Institute of OncologyBudapest, Hungary.
[Godeny, Maria] National Institute of OncologyBudapest, Hungary.
[Szasz, Andras] Szt. Istvan University, Biotechnics DepartmentGodollo, Hungary.
[Lang, Istvan] National Institute of OncologyBudapest, Hungary.
RP Rubovszky, G (reprint author), National Institute of Oncology, Budapest, Hungary.
EM garub@oncol.hu
CR Wakelee HA, Bernardo P, Johnson DH et al, 2006, Changes in the natural history of nonsmall cell lung cancer, NSCLC)–comparison of outcomes and characteristics in patients with advanced NSCLC entered in Eastern Cooperative Oncology Group trials before and after 1990. Cancer 06:2208–2217
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An SJ, Huang YS, Chen ZH, 2011, et al. Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy, Med Oncol [Epub ahead of print]
Horn L, Dahlberg SE, Sandler AB et al, 2009, Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. J Clin Oncol 27:6006– 6011
Herbst RS, Ansari R, Bustin F et al, 2011, Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-smallcell lung cancer after failure of standard first-line chemotherapy, BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet 377:1846–1854
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 119
EP 122
DI 10.1007/s12253-012-9551-7
PG 4
ER
PT J
AU Haltrich, I
Csoka, M
Kovacs, G
Torok, D
Alpar, D
Ottoffy, G
Fekete, Gy
AF Haltrich, Iren
Csoka, Monika
Kovacs, Gabor
Torok, Dora
Alpar, Donat
Ottoffy, Gabor
Fekete, Gyorgy
TI Six Cases of Rare Gene Amplifications and Multiple Copy of Fusion Gene in Childhood Acute Lymphoblastic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Childhood ALL; Gene amplification; FISH; Subtle rearrangement
ID Childhood ALL; Gene amplification; FISH; Subtle rearrangement
AB Cytogenetic aberrations are very important factors in risk assessment of childhood hematological malignancies. We report six childhood acute lymphoid leukemia (ALL) cases with rare cytogenetic aberrations: five with RUNX1, ABL1 or MLL proto-oncogene amplification and one case of multiple copies of ETV6/RUNX1 fusion genes. The simultaneous presence of two adverse genetic aberrations is of special interest: ETV6-RUNX1 fusion gene is associated with good prognosis and intrachromosomal amplification of the homologue RUNX1 gene is associated with poor prognosis. We also report a patient with MLL amplification, a unique finding in childhood T-ALL. Report of these subtle rearrangements contributes to our understanding of diagnostic and prognostic significance of these rare cytogenetic abnormalities.
C1 [Haltrich, Iren] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, 1094 Budapest, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, 1094 Budapest, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, 1094 Budapest, Hungary.
[Torok, Dora] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, 1094 Budapest, Hungary.
[Alpar, Donat] University of Pecs, Department of PathologyPecs, Hungary.
[Ottoffy, Gabor] University of Pecs, Department of PediatricsPecs, Hungary.
[Fekete, Gyorgy] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, 1094 Budapest, Hungary.
RP Haltrich, I (reprint author), Semmelweis University, 2nd Department of Pediatrics, 1094 Budapest, Hungary.
EM haltrich.iren@med.semmelweis-univ.hu
CR Bruyere H, Sutherland H, Chipperfield K, Hudoba M, 2010, Concomitant and successive amplifications of MYC in APL-like leukemia. Cancer Genet Cytogenet 197:75–80
Gebhart E, 2005, Double minutes, cytogenetic equivalents of gene amplification, in human neoplasia - a review. Clin Transl Oncol 7:477–485
Attarbaschi A, Mann G, Panzer-Grumayer R et al, 2008, Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin- Frankfurt-Munster, ALL-BFM, trials. J Clin Oncol 26:3046–3050
Mohamed A, 2010, MLL amplification in leukemia. Atlas Genet Cytogenet Oncol Haematol. URL: http://AtlasGeneticsOncology.org/ Anomalies/MLLampliID1547.html
Moorman AV, Ensor HM, Richards SM et al, 2010, Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol 11:429–438
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Attarbaschi A, Mann G, Konig M et al, 2004, Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis. Leukemia 18:1611–1616
Al-Sweedan SA, Neglia JP et al, 2007, Characteristics of patients with TEL-AML1-positive acute lymphoblastic leukemia with single or multiple fusions. Pediatr Blood Cancer 48:510–514
Moorman AV, Richards SM, Robinson HM et al, 2007, Prognosis of children with acute lymphoblastic leukemia, ALL, and intrachromosomal amplification of chromosome 21, iAMP21). Blood 109:2327–2330
Mikhail FM, Serry KA, Hatem N et al, 2002, AML1 gene overexpression in childhood acute lymphoblastic leukemia. Leukemia 16:658–668
PaisAP,Amare KadamPS, RajeGC et al, 2008, RUNX1 aberrations in ETV6/RUNX1-positive and ETV6/RUNX1-negative patients: its hemato-pathological and prognostic significance in a large cohort, 619 cases, of ALL. Pediatr Hematol Oncol 25:582–597
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Bernasconi P, Calatroni S, Giardini I et al, 2005, ABL1 amplification in T-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet 162:146–150
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Cuthbert G, Thompson K, McCullough S et al, 2000, MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Group, UKCCG, study. Leukemia 14:1885–1891
Espinet B, Florensa L, Salido M, Sole F, 2003, MLL intrachromosomal amplification in a pre-B acute lymphoblastic leukemia. Haematologica 88:EIM03
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 123
EP 128
DI 10.1007/s12253-012-9533-9
PG 6
ER
PT J
AU Kontic, M
Stojsic, J
Stevic, R
Bunjevacki, V
Jekic, B
Dobricic, V
AF Kontic, Milica
Stojsic, Jelena
Stevic, Ruza
Bunjevacki, Vera
Jekic, Biljana
Dobricic, Valerija
TI Could Spindle Cell Lung Carcinoma be Considered and Treated as Sarcoma, According to its Clinical Course, Morphology, Immunophenotype and Genetic Finding?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Spindle cell lung carcinoma; Immunophenotype; Oncogenetic; p53; Sarcoma
ID Spindle cell lung carcinoma; Immunophenotype; Oncogenetic; p53; Sarcoma
AB The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment.
C1 [Kontic, Milica] Clinical Centre of Serbia, Institute for Lung Diseases and TuberculosisBelgrade, Serbia.
[Stojsic, Jelena] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Stevic, Ruza] Clinical Centre of Serbia, Institute of RadiologyBelgrade, Serbia.
[Bunjevacki, Vera] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Jekic, Biljana] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Dobricic, Valerija] University in Belgrade, Medical Faculty, Clinical Centre of Serbia, Institute of NeurologyBelgrade, Serbia.
RP Kontic, M (reprint author), Clinical Centre of Serbia, Institute for Lung Diseases and Tuberculosis, Belgrade, Serbia.
EM milicakontic@yahoo.com
CR Mainwaring MG, Poor C, Zander DS, Harman E, 2000, Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest 117:591–593
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Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC et al, 2004, World health organisation classification of tumours. Pathology and genetics of the lung, pleura, thymus and heart. IARC Press, Lyon, pp 512–536
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Stojsic J, Stevic R, Kontic M, Stojsic Z, Drndarevic N, Bunjevacki V, Jekic B, 2011, Large cell lung carcinoma with unusual imaging feature. Immunophenotype and genetic finding. Pathol Oncol Res 17:175–179
Kim TS, Han J, Lee KS, Jeong YJ, Kwak SH, Byun HS, ChungMJ, Kim H, Kwon OJ, 2005, CT findings of surgically resected pleomorphic carcinoma of the lung in 30 patients. AJR 185:120–125
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Venissac N, Pop D, 2007, Sarcomatoid lung cancer, spindle/giant cells): an aggressive disease? J Thorac Cardiovasc Surg 134:619– 623
Kontic M, Stojsic J, Kacar-Kukric V, Jekic B, Bunjevacki V, 2010, Multidisciplinary approach in diagnosis of lung carcinoma. Exp Oncol 32:111–113
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 129
EP 133
DI 10.1007/s12253-012-9562-4
PG 5
ER
PT J
AU Villaran, J
Loaiza-Bonilla, A
Parra-Herran, C
Pinto, A
AF Villaran, Jorge
Loaiza-Bonilla, Arturo
Parra-Herran, Carlos
Pinto, Andre
TI Pelvic Angiosarcoma Occurring in a Postmenopausal Female: Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
C1 [Villaran, Jorge] University of Miami, Jackson Health System MiamiMiami, FL, USA.
[Loaiza-Bonilla, Arturo] University of Miami, Jackson Health System MiamiMiami, FL, USA.
[Parra-Herran, Carlos] Brigham and Women’s Hospital, Department of PathologyBoston, MA, USA.
[Pinto, Andre] University of Miami, Jackson Health System MiamiMiami, FL, USA.
RP Pinto, A (reprint author), University of Miami, Jackson Health System Miami, Miami, USA.
EM Apinto1@med.miami.edu
CR Mankin H, Hornicek F, 2005, Diagnosis, classification, and management of soft tissue sarcomas. Cancer Control 12(1):5– 21
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Young R, Brown N, Reed M et al, 2010, Angiosarcoma. Lancet Oncol 11:983–91
Hart J, Mandavilli S, 2011, Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med 135(2):268–72
Cambruzzi E, Pegas KL, Milani DM, Cruz RP, Guerra EH, Ferrari MB, 2010, Angiosarcoma arising in an ovarian fibroma: a case report. Pathol Res Int 842592
Bradford L, Swartz K, Rose S, 2010, Primary angiosarcoma of the ovary complicated by hemoperitoneum: a case report and review of the literature. Arch Gynecol Obstet 281:145–150
Bosmuller H, Gruber C, Haitchi-Petnehazy S, Dietmar Wagner D, Webersinke G, Hauptmann S, 2011, Primary angiosarcoma of the ovary with prominent fibrosis of the ovarian stroma. Case report of an 81-year old patient. Diagn Pathol 6:65–71
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Penel N, Marreaud S, Robin YM et al, 2011, Angiosarcoma: state of the art and perspectives. Crit Rev Oncol Hematol 80(2):257–63
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Sood A, Sorosky J, Gelder M et al, 1998, Primary ovarian sarcoma: analysis of prognostic variables and the role of surgical cytoreduction. Cancer 82(9):1731–7
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Bradford L, Swartz K, Rose S, 2010, Primary angiosarcoma of the ovary complicated by hemoperitoneum: a case report and review of the literature. Arch Gynecol Obstet 281:145–150
Serrano C, Garcia A, Brana I et al, 2010, Angiosarcoma of the ovary: is it always a lethal disease? J Clin Oncol 28(33):e675–e677
Cambruzzi E, Pegas KL, Milani DM et al, 2010, Angiosarcoma arising in an ovarian fibroma: a case report. Pathol Res Int 2010:842592
Kiesel H, Muller AM, Schmitt-Graeff A et al, 2009, Dramatic and durable efficacy of imatinib in an advanced angiosarcoma without detectable KIT and PDGFRA mutations. Cancer Biol Ther 8:319–321
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2013
VL 19
IS 1
BP 135
EP 139
DI 10.1007/s12253-012-9540-x
PG 5
ER
PT J
AU Balogh, P
Katz, S
Kiss, LA
AF Balogh, Peter
Katz, Sandor
Kiss, L Anna
TI The Role of Endocytic Pathways in TGF-β Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE TGF-β; EMT; Endocytosis; Early endosome; Caveolae
ID TGF-β; EMT; Endocytosis; Early endosome; Caveolae
AB Transforming growth factor β (TGF-β) superfamily consists of numerous cytokins that regulate various cellular processes. TGF-β, the prototype of the family, signals through its cell surface serine/threonin kinase receptors and besides its role in cell differentiation, migration, adhesion etc. it is also able to induce epithelial-mesenchymal (EMT) transition via both Smadpathway and MAPK- pathway. Among the different types of epithelial-mesenchymal transition, type II that is described to be associated with wound healing, tissue regeneration, organ fibrosis and is induced upon inflammatory stimuli. It can be triggered by secretion of growth factors such as TGF-β, EGF. Different endocytic routes are used for the internalization of TGF-β ligand and its receptors and these pathways can control the activity of downstream events. Internalization via clathrin-coated vesicles promotes the signaling while the caveolamediated endocytosis plays important role in the termination of the events, although the steps of the latter event are less clear. The early endosome is considered a clue compartment in promoting the signaling. Recently published data suggest that the early endosome plays crucial role in the termination of the TGFβ signaling as well. It is not only maintain a special environment for the effective signaling but can direct the internalized cargos towards degradative pathways (multivesicular bodies, lysosomes).
C1 [Balogh, Peter] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58, 1094 Budapest, Hungary.
[Katz, Sandor] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58, 1094 Budapest, Hungary.
[Kiss, L Anna] Semmelweis University, 1st Department of Anatomy, Tuzolto u. 58, 1094 Budapest, Hungary.
RP Balogh, P (reprint author), Semmelweis University, 1st Department of Anatomy, 1094 Budapest, Hungary.
EM balogh.petra@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 141
EP 148
DI 10.1007/s12253-012-9595-8
PG 8
ER
PT J
AU Zamanian, M
Veerakumarasivam, A
Syahril, A
Rosli, R
AF Zamanian, Mohammadreza
Veerakumarasivam, Abhi
Syahril, Abdullah
Rosli, Rozita
TI Calreticulin and Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Calreticulin; Endoplasmic reticulum; Cancer; Malignant progression; Invasion; Metastasis
ID Calreticulin; Endoplasmic reticulum; Cancer; Malignant progression; Invasion; Metastasis
AB Calreticulin (CRT) as a multi-functional endoplasmic reticulum protein is involved in a spectrum of cellular processes which ranges from calcium homeostasis and chaperoning to cell adhesion and finally malignant formation and progression. Previous studies have shown a contributing role for CRT in a range of different cancers. This present review will focus on the possible roles of CRT in the progression of malignant proliferation and the mechanisms involved in its contribution to cancer invasion.
C1 [Zamanian, Mohammadreza] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Genetic Medicine Research Center, 43400 Selangor, Serdang, Malaysia.
[Veerakumarasivam, Abhi] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Genetic Medicine Research Center, 43400 Selangor, Serdang, Malaysia.
[Syahril, Abdullah] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Genetic Medicine Research Center, 43400 Selangor, Serdang, Malaysia.
[Rosli, Rozita] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Genetic Medicine Research Center, 43400 Selangor, Serdang, Malaysia.
RP Rosli, R (reprint author), Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Genetic Medicine Research Center, 43400 Selangor, Malaysia.
EM rozita@medic.upm.edu.my;r_rosli@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 149
EP 154
DI 10.1007/s12253-012-9600-2
PG 6
ER
PT J
AU Singh, KA
Pandey, A
Tewari, M
Kumar, R
Sharma, A
Pandey, PH
Shukla, ShH
AF Singh, Kumar Alok
Pandey, Anshuman
Tewari, Mallika
Kumar, Rajiv
Sharma, Anjana
Pandey, P H
Shukla, Shankar Hari
TI Prospects of Nano–Material in Breast Cancer Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Nano materials; Breast cancer; Biomarkers; Diagnosis
ID Nano materials; Breast cancer; Biomarkers; Diagnosis
AB Breast cancer evaluation and early diagnosis are core complexity worldwide and an ambiguity for scientists till date. Nano-materials are innovative tools for rapid diagnosis and therapy, which may induce an immense result in the field of oncology. Their exceptional size-dependent properties make them special and superior materials and quite indispensable in several fields of the human activities. The major obstacle in finding cure for malignant breast cancer is to increase in development of resistances for tumors to the therapeutic treatments. The widespread mammo-graph particle is being developed by nations to diagnosis disease in primitive stage to decline the mortality rates caused by breast carcinoma. The advancement of nano-particle based diagnostic tools facilitates in evaluation and provides encouraging development in breast cancer therapeutics. In this compact review, efforts have been made to compose the current advancements in the area of functional nano-particles. Furthermore, in vivo and in vitro applications of nano-materials in breast cancer management are also discussed.
C1 [Singh, Kumar Alok] Banaras Hindu University, Institute of Medical Sciences, Department of Surgical Oncology, 221005 Varanasi, India.
[Pandey, Anshuman] Banaras Hindu University, Institute of Medical Sciences, Department of Surgical Oncology, 221005 Varanasi, India.
[Tewari, Mallika] Banaras Hindu University, Institute of Medical Sciences, Department of Surgical Oncology, 221005 Varanasi, India.
[Kumar, Rajiv] Amity University, Amity Institute of Biotechnology, Lucknow CampusLucknow, UP, India.
[Sharma, Anjana] Amity University, Amity Institute of Biotechnology, Lucknow CampusLucknow, UP, India.
[Pandey, P H] Banaras Hindu University, Faculty of Science, Department of BiochemistryVaranasi, India.
[Shukla, Shankar Hari] Banaras Hindu University, Institute of Medical Sciences, Department of Surgical Oncology, 221005 Varanasi, India.
RP Shukla, ShH (reprint author), Banaras Hindu University, Institute of Medical Sciences, Department of Surgical Oncology, 221005 Varanasi, India.
EM wfsos1@gmail.com;harishukla@usa.net
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 155
EP 165
DI 10.1007/s12253-013-9609-1
PG 11
ER
PT J
AU Aiad, AH
Bashandy, AM
Abdou, GA
Zahran, AA
AF Aiad, A Hayam
Bashandy, A Manar
Abdou, Gaber Asmaa
Zahran, A Ahmad
TI Significance of AgNORs and Ki-67 Proliferative Markers in Differential Diagnosis of Thyroid Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ag NORs; Ki 67 labeling index; Follicular carcinoma; Follicular adenoma; Papillary carcinoma
ID Ag NORs; Ki 67 labeling index; Follicular carcinoma; Follicular adenoma; Papillary carcinoma
AB We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study included: 25 papillary carcinomas, 7 follicular carcinomas, 21 follicular adenomas and 27 nodular goiters. Using a semiautomatic image analysis system, Ag NORs parameters were measured and calculated including: total area of AgNORs, mean Ag NOR number in nuclei, nuclear area, mean area of AgNOR dots per each nucleus, number of central and marginal AgNOR dots, and the relative ratio of total area of AgNOR dots/total area of nucleus. Ki67 immunostaining was performed and the LI was determined. There was a significant difference between groups of thyroid lesions regarding total area of AgNORs, Ag NOR number and number of marginal Ag NOR dots. According to receiver operating characteristic curve, Ag NORs number 02.91 and marginal Ag NORs02.67 were useful cut off values above which follicular carcinoma can be diagnosed with 100 % sensitivity, 79 % specificity, 76 % PPV, 100 % NPV and 85 % diagnostic accuracy for both parameters. Mean Ki67 LI in our study was 14.12±2.29, 61.42±3.77, 34.90±3.49 and 18.60±1.96 for papillary carcinoma, follicular carcinoma, follicular adenoma and nodular goiter respectively. Ki67 LI showed statistically significant difference between follicular carcinoma and follicular adenoma (p<0.026) and between papillary carcinoma and follicular adenoma (p<0.007). Quantification of Ag NORs and Ki67 LI could be used as helpful ancillary methods in the differentiation between different thyroid lesions.
C1 [Aiad, A Hayam] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
[Bashandy, A Manar] Menoufiya University, Faculty of Medicine, Department of AnatomyShebein Elkom, Egypt.
[Abdou, Gaber Asmaa] Menoufiya University, Faculty of Medicine, Department of PathologyShebein Elkom, Egypt.
[Zahran, A Ahmad] Shebin El-Kom Educational Hospital, ENT DepartmentShebein Elkom, Egypt.
RP Aiad, AH (reprint author), Menoufiya University, Faculty of Medicine, Department of Pathology, Shebein Elkom, Egypt.
EM hayamaiad@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 167
EP 175
DI 10.1007/s12253-012-9565-1
PG 9
ER
PT J
AU Youlin, K
Jianwei, Z
Xin, G
Li, Z
Xiaodong, W
Xiuheng, L
Hengchen, Z
Zhiyuan, Ch
AF Youlin, Kuang
Jianwei, Zhang
Xin, Gou
Li, Zhang
Xiaodong, Weng
Xiuheng, Liu
Hengchen, Zhu
Zhiyuan, Chen
TI 4-1BB Protects Dendritic Cells from Prostate Cancer-Induced Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dendritic cells; Co-stimulatory molecules; 4-1BB; Prostate cancer
ID Dendritic cells; Co-stimulatory molecules; 4-1BB; Prostate cancer
AB It has been shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DCs), which are responsible for the induction of specific antitumor immune responses. Here, we investigated the function of 4-1BB on protecting DCs from prostate cancer-induced apoptosis with an agonistic mAb to 4-1BB. RM-1 cells and DCs were coincubated for 48 h and DC apoptosis was assessed by Annexin Vassay. TNF-α and IL-12 production were assessed by enzyme-linked immunosorbent assay (ELISA) and Bcl-2 and Bcl-xL on DCs were analyzed by Western blot. We have shown that co-incubation of RM-1 cells with DCs is accompanied by an increased level of DCs apoptosis. Triggering 4-1BB on DCs resulted in increased resistance of DCs to RM-1 cells-induced apoptosis, which was owing to the up-regulated expression of Bcl-2 and Bcl-xL, and increased secretion of TNF-αand IL-12. These results demonstrate that triggering 4-1BB on DCs could increased resistance of DCs to PCa-induced apoptosis.
C1 [Youlin, Kuang] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
[Jianwei, Zhang] First Affiliated Hospital of Zhengzhou University, Department of UrologyZhengzhou, China.
[Xin, Gou] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
[Li, Zhang] Wuhan University, Renmin Hospital, Department of UrologyWuhan, China.
[Xiaodong, Weng] Wuhan University, Renmin Hospital, Department of UrologyWuhan, China.
[Xiuheng, Liu] Wuhan University, Renmin Hospital, Department of UrologyWuhan, China.
[Hengchen, Zhu] Wuhan University, Renmin Hospital, Department of UrologyWuhan, China.
[Zhiyuan, Chen] Wuhan University, Renmin Hospital, Department of UrologyWuhan, China.
RP Xin, G (reprint author), Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
EM kyl361@163.com
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Amdur RJ, Parsons JT, Fitzgerald LT et al, 1990, The effect of overall treatment time on local control in patients with adenocarcinoma of the prostate treated with radiation therapy. Int J Radiat Oncol Biol Phys 19:1377–1382
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Lee SW, Park Y, So T et al, 2008, Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells. Nat Immunol 9:917–926
Choi BK, Kim YH, Kwon PM et al, 2009, 4-1BB functions as a survival factor in dendritic cells. J Immunol 182:4107–4115
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 177
EP 181
DI 10.1007/s12253-012-9566-0
PG 5
ER
PT J
AU Mahjabeen, I
Baig, MR
Masood, N
Sabir, M
Inayat, U
Malik, AF
Kayani, AM
AF Mahjabeen, Ishrat
Baig, Mehmood Ruqia
Masood, Nosheen
Sabir, Maimoona
Inayat, Uzma
Malik, Arshad Faraz
Kayani, Akhtar Mahmood
TI Genetic Variations in XRCC1 Gene in Sporadic Head and Neck Cancer (HNC) Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HNC; SSCP; DNA; Carcinogenesis; Mutational analysis; XRCC1
ID HNC; SSCP; DNA; Carcinogenesis; Mutational analysis; XRCC1
AB DNA repair gene polymorphisms have been implicated as susceptibility factors in cancer development. It is possible that DNA repair polymorphisms may also influence the risk of gene mutation. Polymorphisms in the DNA repair gene XRCC1 have been indicated to have a contributive role in DNA adduct formation and an increased risk of cancer development. 300 head and neck cancer patients and 150 controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole exonic region of XRCC1 in head and neck cancer patients. Sequence analysis revealed two missense and two silent mutations in our study. Frequency of silent mutations; Pro206Pro (rs915927) and Gln632Gln (rs3547) was calculated as 0.16 (16 %) and 0.30 (30 %) respectively. Whereas, the frequency of missense mutations; Arg399Gln (rs25487) and Tyr576Asn (rs2307177) was calculated as 0.27 (27 %) and 0.28 (28 %) respectively. In our study, incidence of these mutations was found higher in larynx cancer (p<0.005) as compared to oral cavity and pharynx cancer. Our finding suggests that the polymorphic XRCC1 gene may contribute to risk of developing head and neck cancer. To our knowledge, this is the first report that XRCC1 is associated with increased risk of head and neck cancer in a Pakistani population.
C1 [Mahjabeen, Ishrat] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Baig, Mehmood Ruqia] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Masood, Nosheen] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Sabir, Maimoona] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Inayat, Uzma] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Malik, Arshad Faraz] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
[Kayani, Akhtar Mahmood] COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics LabIslamabad, Pakistan.
RP Kayani, AM (reprint author), COMSATS Institute of Information Technology, Department of Biosciences, Cancer Genetics Lab, Islamabad, Pakistan.
EM mkayani@comsats.edu.pk
CR Parkin DM, Pisani P, Ferley J, 1999, Global cancer statistics. CA Cancer J Clin 49:33–64
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 183
EP 188
DI 10.1007/s12253-012-9567-z
PG 6
ER
PT J
AU Chaisuparat, R
Rojanawatsirivej, S
Yodsanga, S
AF Chaisuparat, Risa
Rojanawatsirivej, Somsri
Yodsanga, Somchai
TI Ribosomal Protein S6 Phosphorylation is Associated with Epithelial Dysplasia and Squamous Cell Carcinoma of the Oral Cavity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ribosomal protein S6; Epithelial dysplasia; Oral squamous cell carcinoma; Tumor progression
ID Ribosomal protein S6; Epithelial dysplasia; Oral squamous cell carcinoma; Tumor progression
AB Ribosomal protein S6 (RPS6), a downstream effector of the mammalian target of rapamycin pathway (mTOR), is activated in many cancers including oral squamous cell carcinoma (OSCC). However, the role of RPS6 in the progression of potentially malignant disorders (or premalignant lesions) to OSCC is unknown. The purpose of this study was to examine the expression of RPS6 in epithelial dysplasia and OSCC to determine the association of RPS6 in tumor progression. In our study, an immunohistochemical analysis of RPS6 was performed on tissue microarrays containing 30 control samples, 15 epithelial dysplasia cases, and 53 OSCC cases. Correlations between the clinicopathologic features of OSCC and RPS6 expression were analyzed using the Chi-square test. We found RPS6 phosphorylation (p-RPS6) in 15/30 (50 %) control normal oral mucosa samples, 15/15 (100 %) epithelial dysplasia cases, and 47/53 (88.68 %) OSCC cases. The frequency of p-RPS6 in epithelial dysplasia or OSCC showed a statistically significant difference compared to control (P<0.001). However, there were no significant correlations between p-RPS6 and the clinicopathologic features of OSCC. Our findings suggest that RPS6 activation is associated with the early events of tumor progression, suggesting p-RPS6 as a potential marker for early detection of oral cancer.
C1 [Chaisuparat, Risa] Chulalongkorn University, Faculty of Dentistry, Department of Oral Pathology, Henry-Dunant Road, Pathumwan, 10330 Bangkok, Thailand.
[Rojanawatsirivej, Somsri] Chulalongkorn University, Faculty of Dentistry, Department of Oral Pathology, Henry-Dunant Road, Pathumwan, 10330 Bangkok, Thailand.
[Yodsanga, Somchai] Chulalongkorn University, Faculty of Dentistry, Department of Oral Pathology, Henry-Dunant Road, Pathumwan, 10330 Bangkok, Thailand.
RP Chaisuparat, R (reprint author), Chulalongkorn University, Faculty of Dentistry, Department of Oral Pathology, 10330 Bangkok, Thailand.
EM risa.c@chula.ac.th
CR Johnson NW, Jayasekara P, Amarasinghe AA, 2011, Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology. Periodontol 2000 57(1):19–37
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Ruvinsky I, Meyuhas O, 2006, Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31:342–348
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Torres-Rendon A, Roy S, Craig GT et al, 2009, Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas. Br J Cancer 100:1128–1134
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 189
EP 193
DI 10.1007/s12253-012-9568-y
PG 5
ER
PT J
AU Li, L
Zhang, A
Cao, X
Chen, J
Xia, Y
Zhao, H
Shen, A
AF Li, Liren
Zhang, Aixian
Cao, Xiaolei
Chen, Jing
Xia, Yunfei
Zhao, Hui
Shen, Aiguo
TI General Transcription Factor IIB Overexpression and a Potential Link to Proliferation in Human Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma (HCC); General transcription factor IIB (TFIIB); Cell proliferation; Pathogenesis
ID Human hepatocellular carcinoma (HCC); General transcription factor IIB (TFIIB); Cell proliferation; Pathogenesis
AB The general transcription factor IIB (TFIIB) plays a central role in preinitiation complex (PIC) assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II (RNA POLII). TFIIB functionally counteracts the transcriptional activation of hepatitis B virus X protein (HBx), which has been shown to play a role in the development of human hepatocellular carcinoma (HCC). However, the function of TFIIB in HCC remains unclear. In this article, we demonstrate that TFIIB plays an important role in HCC pathogenesis. TFIIB expression was immunohistochemically examined in a series of 100 HCC tissue specimens. The expression level of TFIIB showed significant correlation with the histological grade (P<0.030), the level of AFP (P<0.011) and the proliferation marker Ki-67 (P<0.0002). High TFIIB expression level correlated with poor survival. Western blot analysis also confirmed that the TFIIB protein was overexpressed in HCC tissue compared to benign normal tissue. Additionally, Western blot and qRT-PCR analyses showed a high expression level of TFIIB protein in the HCC cell lines SMMC7721, HepG2, BEL7404, and Huh7 and the immortalized normal line BEL7702 but a lower expression in the normal Chang hepatocyte cell line. Following the release of Huh7 cells from serum starvation, the expression of TFIIB was upregulated. A cell growth assay suggested that TFIIB was involved in the proliferation and growth of HCC cells. In conclusion, our results demonstrate that TFIIB overexpression may play essential roles in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of HCC cells.
C1 [Li, Liren] Affiliated Hospital of Nantong University, Department of Internal Medicine, 226001 Nantong, China.
[Zhang, Aixian] Affiliated Hospital of Nantong University, Department of Internal Medicine, 226001 Nantong, China.
[Cao, Xiaolei] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, China.
[Chen, Jing] Affiliated Hospital of Nantong University, Department of Surgery, 226001 Nantong, China.
[Xia, Yunfei] Affiliated Hospital of Nantong University, Department of Internal Medicine, 226001 Nantong, China.
[Zhao, Hui] Affiliated Hospital of Nantong University, Department of Internal Medicine, 226001 Nantong, China.
[Shen, Aiguo] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, China.
RP Shen, A (reprint author), Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, China.
EM jsntzax@163.com
CR Feng H, Cheng AS, Tsang DP et al, 2011, Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives β-catenin/ T cell factor-dependent hepatocarcinogenesis. J Clin Invest 121:3159–3175
Hsieh A, Kim HS, Lim SO et al, 2011, Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/β-catenin signaling. Cancer Lett 300:162–172
Lau WY, 2000, Primary liver tumors. Semin Surg Oncol 19:135– 144
Llovet JM, Bruix J, 2008, Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48:1312–1327
El-Serag HB, Rudolph KL, 2007, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576
Ueda S, Basaki Y, Yoshie M et al, 2006, PTEN/Akt signaling through epidermal growth factor receptor is prerequisite for angiogenesis by hepatocellular carcinoma cells that is susceptible to inhibition by gefitinib. Cancer Res 66:5346–5353
Baek HJ, Lim SC, Kitisin K et al, 2008, Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology 48:1128–1137
Deng WS, Roberts SGE, 2007, TFIIB and the regulation of transcription by RNA polymerase II. Chromosoma 116:417–429
Albert TK, Grote K, Boeing S et al, 2010, Basal core promoters control the equilibrium between negative cofactor 2 and preinitiation complexes in human cells. Genome Biol 11:R33
Sevilimedu A, Shi H, Lis JT, 2008, TFIIB aptamers inhibit transcription by perturbing PIC formation at distinct stages. Nucleic Acids Res 36:3118–3127
Wang YM, Fairley JA, Roberts SGE, 2010, Phosphorylation of TFIIB links transcription initiation and termination. Curr Biol 20:548–553
Liu X, Bushnell DA, Wang D et al, 2010, Structure of an RNA polymerase II–TFIIB complex and the transcription initiation mechanism. Science 327:206–209
Simone C, Robert OJ, 2010, The linker domain of basal transcription factor TFIIB controls distinct recruitment and transcription stimulation functions. Nucleic Acids Res 39:464–474
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Yang H, Gu J, Zheng Q et al, 2011, RPB5-mediating protein is required for the proliferation of hepatocellular carcinoma cells. J Biol Chem 286:11865–11874
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Wada C, Kasai K, Kameya T et al, 1992, A general transcription initiation factor, human transcription factor IID, overexpressed in human lung and breast carcinoma and rapidly induced with serum stimulation. Cancer Res 52:307–313
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Qadri I, Fatima K, AbdeL-Hafiz H, 2011, Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH. BMC Microbiol 11:48
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 195
EP 203
DI 10.1007/s12253-012-9569-x
PG 9
ER
PT J
AU Ji, HX
Zhao, Q
Pan, JH
Shen, WH
Chen, ZW
Zhou, ZS
AF Ji, Hui-Xiang
Zhao, Qian
Pan, Jin-Hong
Shen, Wen-Hao
Chen, Zhi-Wen
Zhou, Zhan-Song
TI Association of BLCA-4 Hypomethylation in Blood Leukocyte DNA and the Risk of Bladder Cancer in a Chinese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BLCA-4; Hypomethylation; Bladder cancer; Blood leukocyte
ID BLCA-4; Hypomethylation; Bladder cancer; Blood leukocyte
AB Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum, bladder, breast, head and neck, and testicular germ cells. The aim of this study was to examine whether global hypomethylation measured at BLCA-4 repeat regions through bisulfite pyrosequencing in blood leukocyte DNA is associated with the risk of bladder cancer(BC). A total of 312 bladder cancer patients and 361 healthy control subjects were included in Chongqing, China. Global methylation in blood leukocyte DNA was estimated by analyzing BLCA-4 repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing. The median methylation level in BC cases (percentage of 5-methylcytosine (5 mC)075.7 %) was significantly lower than that in controls (79.7 % 5 mC) (P<0.002, Wilcoxon rank-sum test). The odds ratios (ORs) of BC for individuals in the third, second, and first (lowest) quartiles of BLCA-4 methylation were 1.2 (95 % confidence interval (CI) 0.8– 1.9), 1.6 (95 % CI 1.1–2.3), and 2.7 (95 % CI 1.5–3.8) (P for trend <0.001), respectively, compared to individuals in the fourth (highest) quartile. A 2.1-fold (95 % CI 1.5–2.8) increased risk of BC was observed among individuals with BLCA-4 methylation below the median compared to individuals with higher (>median) BLCA-4 methylation. Our results demonstrate for the first time that individuals with global hypomethylation measured in BLCA-4 repeats in blood leukocyte DNA have an increased risk for BC. Our data provide the evidence that BLCA-4 hypomethylation may be a useful biomarker for poor prognosis of patients with BC.
C1 [Ji, Hui-Xiang] Southwest Hospital Affilated to Third Military Medical University, Urology Department, No. 33, Gaotanyanzheng RD, 400038 Chongqing, China.
[Zhao, Qian] Kunming General Hospital of Chengdu Military Region, Urology Department, No. 212, Daguan RD, 650032 Kunming, China.
[Pan, Jin-Hong] Southwest Hospital Affilated to Third Military Medical University, Urology Department, No. 33, Gaotanyanzheng RD, 400038 Chongqing, China.
[Shen, Wen-Hao] Southwest Hospital Affilated to Third Military Medical University, Urology Department, No. 33, Gaotanyanzheng RD, 400038 Chongqing, China.
[Chen, Zhi-Wen] Southwest Hospital Affilated to Third Military Medical University, Urology Department, No. 33, Gaotanyanzheng RD, 400038 Chongqing, China.
[Zhou, Zhan-Song] Southwest Hospital Affilated to Third Military Medical University, Urology Department, No. 33, Gaotanyanzheng RD, 400038 Chongqing, China.
RP Zhou, ZS (reprint author), Southwest Hospital Affilated to Third Military Medical University, Urology Department, 400038 Chongqing, China.
EM zhouzs@yahoo.com.cn
CR Parkin MP, 2008, The global burden of urinary bladder cancer. Scand J Urol Nephrol 42:12–20
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 205
EP 210
DI 10.1007/s12253-012-9570-4
PG 6
ER
PT J
AU Cserni, G
Bezsenyi, I
Marko, L
AF Cserni, Gabor
Bezsenyi, Istvanne
Marko, Laszlo
TI Patients’ Choice on Axillary Lymph Node Dissection Following Sentinel Lymph Node Micrometastasis — First Report on Prospective Use of a Nomogram in Very Low Risk Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sentinel lymph node; Non sentinel lymph node; Micrometastasis; Nomogram; Patient’s choice; Axillary lymph node dissection
ID Sentinel lymph node; Non sentinel lymph node; Micrometastasis; Nomogram; Patient’s choice; Axillary lymph node dissection
AB The optimal locoregional treatment of patients diagnosed with sentinel node (SN) micrometastasis is controversial. A previously reported and validated nomogram was used to calculate the risk of non-SN metastasis in patients with SN micrometastasis over a period of 2 years. Patients were given detailed information about the risk, consequences and treatment options of non-SN involvement, the risk and potential complications of unnecessary completion axillary lymph node dissection (ALND), the imperfectness of the nomogram, and other factors that may influence their selection of further treatment. They also received a questionnaire to monitor factors influencing their decisions. Of the 25 patients participating in the study, 10 have opted for ALND. The only factor that seemed to influence their choice was fear from disease recurrence. Giving detailed information to SN micrometastatic patients is a patient-centered alternative to current recommendations on performing ALND in all such patients or omitting ALND in all of them.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Bezsenyi, Istvanne] University of Szeged, Department of Pathology, Allomas u. 2, 6720 Szeged, Hungary.
[Marko, Laszlo] University of Szeged, Department of Pathology, Allomas u. 2, 6720 Szeged, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, 6000 Kecskemet, Hungary.
EM cserni@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 211
EP 216
DI 10.1007/s12253-012-9571-3
PG 6
ER
PT J
AU Candelier, JJ
Frappart, L
Yadaden, T
Poaty, H
Picard, JY
Prevot, S
Coullin, P
AF Candelier, Jean-Jacques
Frappart, Lucien
Yadaden, Tarik
Poaty, Henriette
Picard, Jean-Yves
Prevot, Sophie
Coullin, Philippe
TI Altered p16 and Bcl-2 Expression Reflects Pathologic Development in Hydatidiform Moles and Choriocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Trophoblast; Uterine cancer; Differentiation; p16; Bcl-2
ID Trophoblast; Uterine cancer; Differentiation; p16; Bcl-2
AB Abnormal trophoblast differentiation is the main cause of gestational trophoblast diseases in the case of hydatidiform moles and choriocarcinomas. Here we investigated the expression patterns of two gene products, p16 and Bcl-2, implicated in cell cycle regulation and apoptosis, respectively, using immunohistochemistry during normal placenta differentiation, hydatidiform moles (partial, complete and invasive) and post-molar choriocarcinomas. The p16 protein shows a gradual expression in cytotrophoblast of normal villous, from a p16 weak proliferative phenotype to a p16 strong invasive phenotype reaching a maximum around 17 weeks of gestation. The expression pattern in cytotrophoblast was similar in moles in contrast to the villous mesenchyme of invasive moles where p16 was strongly expressed. Bcl-2 expression was syncytiotrophoblast specific in normal placenta and moles and increased gradually during normal differentiation. The results explain the persistence of normal and molar villous fragments during their development and their dramatic invasion in the uterine arteries in case of invasive moles. In choriocarcinomas the weak Bcl-2 expression is associated with weak p16 expression indicating a great apoptotic and proliferative potentials. The results suggest that strong p16 expression in the villous mesenchyme may be responsible in part of the morbidity of the moles, and the key of cancer progression in the choriocarcinomas would be a fast cell-cycle turnover.
C1 [Candelier, Jean-Jacques] INSERM U782 Endocrinologie et genetique de la reproduction et du developpement, 32 rue des Carnets, 92140 Clamart, France.
[Frappart, Lucien] Hopital E. Herriot, Service central d’anatomie et de cytologie pathologiques, place d’Arsonval, 69437 Lyon, France.
[Yadaden, Tarik] Centre Hospitalier, Service d’anatomie et de cytologie pathologiques, 194, avenue Rubillard, 72037 Le Mans, France.
[Poaty, Henriette] INSERM U782 Endocrinologie et genetique de la reproduction et du developpement, 32 rue des Carnets, 92140 Clamart, France.
[Picard, Jean-Yves] INSERM U782 Endocrinologie et genetique de la reproduction et du developpement, 32 rue des Carnets, 92140 Clamart, France.
[Prevot, Sophie] Hopital A. Beclere, Service d’anatomie et de cytologie pathologiques, 157 rue de la Porte de Trivaux, 92141 Clamart, France.
[Coullin, Philippe] INSERM U782 Endocrinologie et genetique de la reproduction et du developpement, 32 rue des Carnets, 92140 Clamart, France.
RP Candelier, JJ (reprint author), INSERM U782 Endocrinologie et genetique de la reproduction et du developpement, 92140 Clamart, France.
EM jean-jacques.candelier@u-psud.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 217
EP 227
DI 10.1007/s12253-012-9572-2
PG 11
ER
PT J
AU Obeidat, RB
Matalka, II
Mohtaseb, AA
Al-Kaisi, SN
AF Obeidat, R Basil
Matalka, I Ismail
Mohtaseb, A Alia
Al-Kaisi, S Nabih
TI Selected Immuno-Histochemical Markers in Curettage Specimens and their Correlation with Final Pathologic Findings in Endometrial Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Estrogen receptor; Progesterone receptor; p53; Ki-67; Her2/neu; Endometrial cancer
ID Estrogen receptor; Progesterone receptor; p53; Ki-67; Her2/neu; Endometrial cancer
AB To assess the immuno-histochemical expression of various markers in, endometrial biopsies of patients with endometrial cancer, and to correlate their expression with the final pathologic findings. Sixty-two patients with primary endometrial cancer who underwent surgical treatment were included in this study. Immuno-histochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2, Her-2/neu and Ki-67 were assessed in curettage specimens, and review of the final pathology report from hysterectomy specimens was carried out. The expression of these markers in curettage was correlated with the final tumor characteristics obtained on hysterectomy specimens. Both ER and PR were significantly more expressed in endometrioid type (EC) than nonendometrioid type (NEC) (P value of 0.004 and 0.012). On the contrary, P53, Her-2 and Ki-67 showed higher positivity in NEC than EC (P value of 0.005, 0.025 and 0.002). Positive expression of ER and PR was significantly associated with low grade tumors and superficial myometrial invasion, whereas positive expression of Her-2 and Ki-67 was significantly associated with higher grade lesions, and deep myometrial invasion. Moreover, a statistically significant inverse relationship was observed between the positivity of P53, Her-2 and Ki-67 and the positivity of ER, PR. We found that determination of immuno-histochemical markers in curettage specimens might be helpful in predicting the final pathologic findings in patients with endometrial cancer. This might be helpful in planning the extensivity of the surgery.
C1 [Obeidat, R Basil] Jordan University of Science and Technology, Department of Obstetrics and Gynecology, 21110 Irbid, Jordan.
[Matalka, I Ismail] Jordan University of Science and Technology, Department of Pathology and Laboratory MedicineIrbid, Jordan.
[Mohtaseb, A Alia] Jordan University of Science and Technology, Department of Pathology and Laboratory MedicineIrbid, Jordan.
[Al-Kaisi, S Nabih] King Hussein Cancer Center, Department of PathologyAmman, Jordan.
RP Obeidat, RB (reprint author), Jordan University of Science and Technology, Department of Obstetrics and Gynecology, 21110 Irbid, Jordan.
EM b_obeidat@hotmail.com
CR Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ, 2009, Cancer statistics. CA Cancer J Clin 59(4):225–249
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 229
EP 235
DI 10.1007/s12253-012-9573-1
PG 7
ER
PT J
AU Ji, YI
Lee, BY
Kang, YJ
Jo, JO
Lee, HS
Kim, YH
Kim, YO
Lee, Ch
Koh, BS
Kim, A
Lee, YJ
Jung, HM
Ock, SM
Cha, HJ
AF Ji, Yong-Il
Lee, Bo-Young
Kang, Yun-Jeong
Jo, Jin-Ok
Lee, Ho Sang
Kim, Yeol Heung
Kim, Young-Ok
Lee, Chulmin
Koh, Bong Suk
Kim, Ari
Lee, Young Ji
Jung, Hyung Min
Ock, Sun Mee
Cha, Hee-Jae
TI Expression Patterns of Thymosin β4 and Cancer Stem Cell Marker CD133 in Ovarian Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thymosin β4; CD133; Ovarian cancer; Metastasis; Cancer stem cells; Stomach cancer
ID Thymosin β4; CD133; Ovarian cancer; Metastasis; Cancer stem cells; Stomach cancer
AB Thymosin β4 (Tβ4), a small acidic actin binding peptide, is overexpressed in a side population of cancer stem cells and CD133-positive colorectal cancer stem cells. In order to understand the relationship between Tβ4 and CD133, we studied the expression patterns of Tβ4 and CD133 in ovarian cancers. The expression patterns of Tβ4 and CD133 were studied in normal ovaries, primary ovarian cancers, metastatic ovarian cancers, primary stomach cancers, and normal stomachs by Western blot and immunohistochemistry. Expression patterns and co-localization of Tβ4 and CD133 were examined by immunofluorescence and confocal laser-scanning microscopy. Tβ4 is overexpressed in primary ovarian cancers, but not in primary stomach cancers, when compared with normal controls. However, Tβ4 levels in metastatic stomach cancers to the ovary are significantly upregulated compared with levels in normal stomachs and primary stomach cancers. These results suggest that Tβ4 levels are related to tumorigenesis in ovarian cancers and metastasis in stomach cancers. The expression of Tβ4 in normal ovaries and normal stomachs was weak, but was colocalized with CD133 expression. Tβ4 expression was also co-localized with CD133 expression in primary ovarian carcinomas, metastatic ovarian cancers from stomach cancers and primary stomach cancers. These data suggest that Tβ4 expression is strongly related to CD133 expression and is a characteristic of stem cells or cancer stem cells.
C1 [Ji, Yong-Il] Kosin University College of Medicine, Department of Obstetrics and GynecologyBusan, South Korea.
[Lee, Bo-Young] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Kang, Yun-Jeong] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Jo, Jin-Ok] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Lee, Ho Sang] Kosin University, Department of SurgeryBusan, South Korea.
[Kim, Yeol Heung] Kosin University College of Medicine, Department of Obstetrics and GynecologyBusan, South Korea.
[Kim, Young-Ok] Kosin University College of Medicine, Department of PathologyBusan, South Korea.
[Lee, Chulmin] Inje university, Haeunade Paik Hospital, Department of Obstetrics and GynecologyBusan, South Korea.
[Koh, Bong Suk] Inje university, Sanggye Paik Hospital, Department of Obstetrics and GynecologySeoul, South Korea.
[Kim, Ari] Catholic University of Daegu, School of Medicine, Departments of Obstetrics and GynecologyDaegu, South Korea.
[Lee, Young Ji] Wonkwang University, College of Medicine, Department of Obstetrics and GynecologyIksan, South Korea.
[Jung, Hyung Min] Konkuk University, School of Medicine, Department of Obstetrics and GynecologySeoul, South Korea.
[Ock, Sun Mee] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
[Cha, Hee-Jae] Kosin University College of Medicine, Department of Parasitology and Genetics, 34, Annam-dong, Seo-gu, 602-703 Busan, South Korea.
RP Cha, HJ (reprint author), Kosin University College of Medicine, Department of Parasitology and Genetics, 602-703 Busan, South Korea.
EM hcha@kosin.ac.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 237
EP 245
DI 10.1007/s12253-012-9574-0
PG 9
ER
PT J
AU Aneiros-Fernandez, J
Arias-Santiago, S
Arias-Santiago, B
Herrero-Fernandez, M
Carriel, V
Aneiros-Cachaza, J
Lopez-Valverde, A
Cutando-Soriano, A
AF Aneiros-Fernandez, Jose
Arias-Santiago, Salvador
Arias-Santiago, Borja
Herrero-Fernandez, Maria
Carriel, Victor
Aneiros-Cachaza, Jose
Lopez-Valverde, Antonio
Cutando-Soriano, Antonio
TI MT1 Melatonin Receptor Expression in Warthin’s Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Melatonin; MT1 receptor; Normal parotid gland
ID Immunohistochemistry; Melatonin; MT1 receptor; Normal parotid gland
AB We contribute the first immunohistochemical study of MT1 melatonin receptor in Warthin’s tumor and normal parotid gland. All 14Warthin’s tumors studied showed intense cytoplasmic positivity for MT1 receptor in all cylindrical epithelial cells lining spaces and a less intense positivity in basal cells. The lymphoid component accompanying the tumor was always negative for MT1 receptor. The parotid structure surrounding the tumor showed intense cytoplasmic positivity in all cells lining excretory ducts (lobar and lobulillar), with a lesser and focal positivity in cells of the acinar component. The biological activity of MT1 receptor in epithelial cells lining parotid excretory ducts may resemble its activity in Warthin’s tumor cells.Hence, we propose Warthin’s tumor as a useful positive control in immunohistochemical studies of MT1 melatonin receptor.
C1 [Aneiros-Fernandez, Jose] San Cecilio University Hospital, Department of PathologyGranada, Spain.
[Arias-Santiago, Salvador] San Cecilio University Hospital, Department of DermatologyGranada, Spain.
[Arias-Santiago, Borja] University of Granada, School of DentistryGranada, Spain.
[Herrero-Fernandez, Maria] University of Granada, School of DentistryGranada, Spain.
[Carriel, Victor] University of Granada, Tissue Engineering GroupGranada, Spain.
[Aneiros-Cachaza, Jose] San Cecilio University Hospital, Department of PathologyGranada, Spain.
[Lopez-Valverde, Antonio] University of Salamanca, School of DentistrySalamanca, Spain.
[Cutando-Soriano, Antonio] University of Granada, School of DentistryGranada, Spain.
RP Cutando-Soriano, A (reprint author), University of Granada, School of Dentistry, Granada, Spain.
EM acutando@ugr.es
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Cutando A, Aneiros-Fernandez J, Lopez-Valverde A, Arias- Santiago S, Aneiros-Cachaza J, Reiter RJ, 2011, A new perspective in Oral health: potentialimportance and actions of melatonin receptors MT1, MT2, MT3, and RZR/ROR in the oral cavity. Arch Oral Biol 56:944–950
Cutando A, Aneiros-Fernandez J, Aneiros-Cachaza J, Arias- Santiago S, 2011, Melatonin and cancer: current knowledge and its application to oral cavity tumours. J Oral Pathol Med 40(8):593–597
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Sobrinho-Simoes M, Maximo V, 2006, Warthin’s tumour. Virchows Arch 448:877–878
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 247
EP 250
DI 10.1007/s12253-012-9575-z
PG 4
ER
PT J
AU Huang, XB
Li, J
Zheng, L
Zuo, GH
Han, KQ
Li, HY
Liang, P
AF Huang, Xiao-Bing
Li, Jing
Zheng, Lu
Zuo, Guo-Hua
Han, Ke-Qiang
Li, Hong-Yan
Liang, Ping
TI Bioinformatics Analysis Reveals Potential Candidate Drugs for HCC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Cirrhosis; Sub-pathways; Small molecule drugs
ID Hepatocellular carcinoma; Cirrhosis; Sub-pathways; Small molecule drugs
AB In our study, we used the GSE17967 series to identify differentially expressed genes between cirrhosis and hepatocellular carcinoma, aiming to analyse the mechanism of the progression of cirrhosis to hepatocellular carcinoma and identify the sub-pathways closely related to this progression, and find the small molecule drugs to interfere this progression. From the result of our study, we find that many small molecule drugs closely related with carcinoma have been linked by our method. We also find some new small molecule drugs related to this progression. It is demonstrated that bioinformatics analysis is useful in identification of the candidate drugs in hepatocellular carcinoma.
C1 [Huang, Xiao-Bing] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Li, Jing] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Zheng, Lu] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Zuo, Guo-Hua] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Han, Ke-Qiang] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Li, Hong-Yan] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
[Liang, Ping] Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, NO.2 Xin Qiao Street, Sha Ping Ba District, 400037 Chongqing, China.
RP Liang, P (reprint author), Third Military Medical University, Xinqiao Hospital, Department of Hepatobiliary Surgery, 400037 Chongqing, China.
EM PiangLiang2012@hotmail.com
CR El-Serag HB, Rudolph KL, 2007, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 7):2557–2576., DOI 10.1053/j.gastro.2007.04.061
Avila MA, Berasain C, Sangro B, Prieto J, 2006, New therapies for hepatocellular carcinoma. Oncogene 25(27):3866–3884., DOI 10.1038/sj.onc.1209550
Yuan R, Jiang C, Hong K, Yu X, Wu L, Liu T, Liu X, Tang X, Cai H, Shao J, 2011, Genetic variation in the Fat10 gene is associated with risk of hepatocellular carcinoma in a Chinese population. Asian Pac J Cancer Prev 12(8):2117–2122
Johnson PJ, Williams R, 1987, Cirrhosis and the aetiology of hepatocellular carcinoma. J Hepatol 4(1):140–147
Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M, Donato MF, Piva A, Di Carlo V, Dioguardi N, 1991, Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325(10):675–680., DOI 10.1056/ NEJM199109053251002
Aravalli RN, Steer CJ, Cressman EN, 2008, Molecular mechanisms of hepatocellular carcinoma. Hepatology 48(6):2047–2063., DOI 10.1002/hep. 22580
Spies M, Dasu MR, Svrakic N, Nesic O, Barrow RE, Perez-Polo JR, Herndon DN, 2002, Gene expression analysis in burn wounds of rats. Am J Physiol Regul Integr Comp Physiol 283(4):R918– R930., DOI 10.1152/ajpregu.00170.2002
Llovet JM, Bruix J, 2008, Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48(4):1312–1327., DOI 10.1002/ hep. 22506
Su H, Hu N, Yang HH, Wang C, Takikita M, Wang QH, Giffen C, Clifford R, Hewitt SM, Shou JZ, Goldstein AM, Lee MP, Taylor PR, 2011, Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res 17(9):2955–2966., DOI 10.1158/ 1078-0432.CCR-10-2724
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Smyth GK, 2004, Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:Article3., DOI 10.2202/1544-6115.1027
Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I, 2001, Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125(1–2):279–284
Zhou L, Liu C, Meng FD, Qu K, Tian F, Tai MH, Wei JC, Wang RT, 2012, Long-term prognosis in hepatocellular carcinoma patients after hepatectomy. Asian Pac J Cancer Prev 13(2):483– 486
Dreesen O, Brivanlou AH, 2007, Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3(1):7–17
Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC, 2005, Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45:495–528., DOI 10.1146/annurev.pharmtox.45.120403.095825
Shankar S, Srivastava RK, 2008, Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitorinduced apoptosis. Adv Exp Med Biol 615:261–298., DOI 10.1007/ 978-1-4020-6554-5_13
Minucci S, Pelicci PG, 2006, Histone deacetylase inhibitors and the promise of epigenetic, and more, treatments for cancer. Nat Rev Cancer 6(1):38–51., DOI 10.1038/nrc1779
Marks PA, Breslow R, 2007, Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25(1):84–90., DOI 10.1038/nbt1272
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 251
EP 258
DI 10.1007/s12253-012-9576-y
PG 8
ER
PT J
AU Lu, Y
Sun, G
Liu, G
Shi, Y
Han, Y
Yu, F
Xiang, X
Li, W
Xiao, H
Liu, X
Li, Sh
AF Lu, Yifang
Sun, Guogui
Liu, Geling
Shi, Yanping
Han, Ying
Yu, Fang
Xiang, Xiuxiu
Li, Weijuan
Xiao, Hongzhen
Liu, Xiuling
Li, Sha
TI Clinical Significance of Mannose-Binding Lectin Expression in Thyroid Carcinoma Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid carcinoma; Apoptosis; Mannosebinding lectin
ID Thyroid carcinoma; Apoptosis; Mannosebinding lectin
AB Mannose-binding lectin (MBL) plays an important role in the host defence against pathogens and carcinogenesis. This study aimed to analyze differential expression of MBL protein in thyroid cancer tissues and then to investigate the effects of rhMBL in thyroid cancer cells. Tissue specimens from 45 thyroid carcinoma patients and 45 adenoma patients were recruited for immunohistochemical analysis of MBL expression. Cell viability, apoptosis, RT-PCR and Western blot assays were used to detect changes in tumor cell viability, apoptosis, and gene expression, respectively, after treatment of thyroid cancer cells with rhMBL. MBL was differentially expressed in papillary thyroid carcinoma, adenoma, and the distant normal tissues (0.322±0.008, 0.227±0.003, and 0.113 ±0.003, respectively, P<0.05). MBL expression was associated with the advanced disease stage, histological grade, or lymph nodemetastasis in cancer patients (P<0.05).Moreover, rhMBL treatment of thyroid cancer cells reduced tumor cell viability but induced apoptosis in a dose- and time-dependent manner. rhMBL treatment also downregulated Bcl2 protein expression in thyroid cancer cells (P<0.05). In addition, expression p53 protein was increased in thyroid cancer cells after rhMBL treatment (P<0.05). The data from the current study demonstrate that MBL overexpression is associated with advanced thyroid carcinomas, and rhMBL treatment significantly reduced viability but induced apoptosis of thyroid cancer cell lines. Further studies will clarify whether overexpressed MBL in thyroid cancer tissues is functional.
C1 [Lu, Yifang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Sun, Guogui] Tangshan People’s Hospital, Department of ChemoradiotherapyTangshan, China.
[Liu, Geling] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Shi, Yanping] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Han, Ying] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Yu, Fang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Xiang, Xiuxiu] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Weijuan] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Xiao, Hongzhen] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Liu, Xiuling] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Sha] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
RP Liu, G (reprint author), Tangshan Workers Hospital, Department of Endocrinology (Section I), Tangshan, China.
EM lyf800218@163.com
CR DeLellis RA, Lloyd RV, Heitz PU, Eng C, eds,, 2004, World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. IARC, Lyon
Nikiforov YE, 2009, Thyroid tumors: classification and general considerations. In: Nikiforov YE, Biddinger PW, Thompson LDR, eds, Diagnostic pathology and molecular genetcis of the thyroid. Lippincott Williams & Wilkins, Baltimore, pp 94–102
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA, 2003, High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/ PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63(7):1454–1457
Frattini M, Ferrario C, Bressan P, BalestraD,De Cecco L,Mondellini P, Bongarzone I, Collini P, Gariboldi M, Pilotti S, PierottiMA, Greco A, 2004, Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene 23(44):7436–7440
Loris R, 2002, Principles of styuctures of animal and plant lectins. Biochim Biophys Acta 1572(2-3):198–208
Fujita T, 2002, Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2(5):346–353
Bernig T, Boersma BJ, Howe TM, Welch R, Yadavalli S, Staats B, Mechanic LE, Chanock SJ, Ambs S, 2007, The mannose-binding lectin, MBL2, haplotype and breast cancer: an association study in African American and Caucasian women. Carcinogenesis 28, 4):828–836
Wang FY, Tahara T, Arisawa T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Okubo M, Maruyama N, Kamano T, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Nakano H, Hirata I, 2008, Mannan-binding lectin, MBL, polymorphism and Gastric Cancer Risk in Japanese Population. Dig Dis Sci 53(11):2904–2908
Amon PE, Robyn MM, 2003, Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 37(11):1496–1505
Ma Y, Uemura K, Oka S, Kozutsumi Y, Kawasaki N, Kawasaki T, 1999, Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system:mannan-binding proteindependent cell-mediated cytotoxicity. Biochem 96(2):371–375
Vang Petersen S, Thiel S, Jensenius JC, 2001, The mannanbinding lectin pathway of complement activation: biology and disease association. Mol lmmunol 38(2–3):133–149
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Garcia-Laorden MI, Rua-Figueroa I, Perez-Aciego P, Rodriguez- Perez JC, Citores MJ, Alamo F, Erausquin C, Rodriguez-Gallego C, 2003, Mannose binding lectin polymorphisms as a diseasemodulating facter in women with systemic lupus erythematosus from Canary Islands, Spain. J Rheumatol 30(4):740–746
Tumer MW, 2002, The role of mannose-binding lectin in health and desease. HK J Paediatr 40(7):134–142
Boniotto M, Braida L, Baldas V, Not T, Ventura A, Vatta S, Radillo O, Tedesco F, Percopo S, Montico M, Amoroso A, Crovella S, 2005, Evidence of a correlation between mannose binding lectin and celiac disease: a model for other autoimmune diseases. J Mol Med 83(4):308–315
Stuart LM, Takahashi K, Shi L, Savill J, Ezekowitz RA, 2005, Mannose-binding lectin-deficient mice display defective apoptotic cells. J Immunol 174(6):3220–3226
Koch A, Melbye M, Sorensen P, Homoe P, Madsen HO, Molbak K, Hansen CH, Andersen LH, Hahn GW, Garred P. Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. Uqeskr Laeqer 164(10):5635-5640
van der Zwet WC, Catsburg A, van Elburg RM, Savelkoul PH, Vandenbroucke-Grauls CM, 2008, Mannose binding Lectin, MBL, genotype in relation to risk of nosocomial infection in preterm neonates in the neonatal intensive care unit. Clin Microbiol Infect 14(2):130–135
Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG, 2002, Analysis of the relationship between mannose-binding lectin, MBL, genotype, MBL levels and function in an Australian blood donor population. Seand J Immunol 56(6):630–641
Liu G, Zhang H, Li J, 2006, mRNA differential display cloning of thyroid cancer-related genes. Chin J Clin Oncol 33:621–624
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 259
EP 266
DI 10.1007/s12253-012-9577-x
PG 8
ER
PT J
AU Takacs, T
Paszt, A
Simonka, Zs
Abraham, Sz
Borda, B
Ottlakan, A
Ormandi, K
Lazar, M
Voros, A
Kahan, Zs
Lazar, Gy
AF Takacs, Tibor
Paszt, Attila
Simonka, Zsolt
Abraham, Szabolcs
Borda, Bernadett
Ottlakan, Aurel
Ormandi, Katalin
Lazar, Mate
Voros, Andras
Kahan, Zsuzsanna
Lazar, Gyorgy
TI Radioguided Occult Lesion Localisation Versus Wire-Guided Lumpectomy in the Treatment of Non-Palpable Breast Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-palpable; Breast cancer; Wire-guided localisation; Radioguided occult lesion localisation; Surgical margins
ID Non-palpable; Breast cancer; Wire-guided localisation; Radioguided occult lesion localisation; Surgical margins
AB The purpose of this study was to compare the two methods—guidewire localisation and the radioguided occult lesion localisation—used in the localisation and surgical removal of non-palpable breast tumours. This retrospective study enrolled patients diagnosed with nonpalpable malignant breast tumours. In this study either guidewire localisation (GWL, n069) or radioguided occult lesion localisation (ROLL, n0321) was used for the detection and removal of the tumours. The two methods were compared with regards to preoperative localisation time, operating time, removed specimen volume, the pathological tumour size, the presence of positive surgical margins and postoperative complications. Furthermore, we have also investigated other factors that could have an impact on the frequency of positive resection margins. The localisation time was significantly shorter in the ROLL group, both with ultrasound guidance (5.7±1.44 min vs. 21.6±2.37 min, p<0.05) and with radiographic guidance (21.8±3.1 min vs. 41.6±3.75 min, p<0.021) as well. No significant difference was observed between the two methods in terms of operating time, removed specimen volume and pathological tumour size, or the presence of positive resection margins, or the occurrence of postoperative wound infections. The size of the tumour (ROLL, GWL grps), the presence of a multifocal tumour (ROLL grp), the presence of an extensive in situ breast carcinoma around the invasive cancer (ROLL, GWL grps) and the volume of the removed breast specimen (GWL grp) significantly increased the frequency of positive resection margins. We recommend the use of the ROLL method for the removal of nonpalpable breast tumours as it has a much shorter localisation time, and it is a simpler surgical technique as well.
C1 [Takacs, Tibor] University of Szeged, Department of SurgerySzeged, Hungary.
[Paszt, Attila] University of Szeged, Department of SurgerySzeged, Hungary.
[Simonka, Zsolt] University of Szeged, Department of SurgerySzeged, Hungary.
[Abraham, Szabolcs] University of Szeged, Department of SurgerySzeged, Hungary.
[Borda, Bernadett] University of Szeged, Department of SurgerySzeged, Hungary.
[Ottlakan, Aurel] University of Szeged, Department of SurgerySzeged, Hungary.
[Ormandi, Katalin] Euromedic Diagnostics Hungary LtdSzeged, Hungary.
[Lazar, Mate] Euromedic Diagnostics Hungary LtdSzeged, Hungary.
[Voros, Andras] University of Szeged, Department of PathologySzeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
RP Lazar, Gy (reprint author), University of Szeged, Department of Surgery, Szeged, Hungary.
EM lg@surg.szote.u-szeged.hu
CR Verkooijen HM, Peeters PHM, Pijnappel RM, Koot VCM, Schipper MEI, Rinkes IHMB, 2000, Diagnostic accuracy of needle-localized open breast biopsy for impalpable breast disease. Br J Surg 87(3):344–347
Kopans DB, DeLuca S, 1980, A modified needle-hook wire technique to simplify preoperative localisation of occult breast lesions. Radiology 134(3):781
Zurrida S, Galimberti V, Monti S, Luini, 1998, A radioguided localisation of occult breast lesions. Breast 7(1):11–13
Gennari R, Galimberti V, De Cicco C, Zurrida S, Zerwes F, Pigatto F et al, 2000, Use of technetium-99m-labeled colloid albumin for preoperative and intraoperative localisation of nonpalpable breast lesions. J Am Coll Surg 190(6):692–698, discussion 698–699
Ronka R, Krogerus L, Leppanen E, von Smitten K, Leidenius M, 2004, Radio-guided occult lesion localisation in patients undergoing breast-conserving surgery and sentinel node biopsy. Am J Surg 187(4):491–496
Gallegos Hernandez JF, Tanis PJ, Deurloo EE, Nieweg OE, Th Rutgers EJ, Kroon BB et al, 2004, Radio-guided surgery improves outcome of therapeutic excision in non-palpable invasive breast cancer. Nucl Med Commun 25(3):227–232
Zgajnar J, Hocevar M, Frkovic-Grazio S, Hertl K, Schweiger E, Besic N, 2004, Radioguided occult lesion localisation, ROLL, of the nonpalpable breast lesions. Neoplasma 51:385–389
Nadeem R, Chagla LS, Harris O, Desmond S, Thind R, Titterrell C et al, 2005, Occult breast lesions: a comparison between radioguided occult lesion localisation, ROLL, vs. wire-guided lumpectomy, WGL). Breast 14(4):283–289
Thind CR, Desmond S, Harris O, Nadeem R, Chagla LS, Audisio RA, 2005, Radio-guided localisation of clinically occult breast lesions, ROLL): a DGH experience. Clin Radiol 60:681–686
Medina-Franco H, Abarca-Perez L, Garcia-Alvarez MN, Ulloa- Gomez JL, Romero-Trejo C, Sepulveda-Mendez J, 2008, Radioguided occult lesion localisation, ROLL, versus wireguided lumpectomy for non-palpable breast lesions: a randomized prospective evaluation. J Surg Oncol 97(2):108–111
De Cicco C, Trifiro G, Intra M, Marotta G, Ciprian A, Frasson A et al, 2004, Optimised nuclear medicine method for tumor marking and sentinel node detection in occult primary breast lesions. Eur J Nucl Med Mol Imaging 31(3):349–354
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Luini A, Zurrida S, Paganelli G, Galimberti V, Sacchini V, Monti S et al, 1999, Comparison of radioguided excision with wire localisation of occult breast lesions. Br J Surg 86(4):522–525
Rampaul RS, Bagnall M, Burrell H, Pinder SE, Evans AJ, Macmillan RD, 2004, Randomized clinical trial comparing radioisotope occult lesion localisation and wire-guided excision for biopsy of occult breast lesions. Br J Surg 91(12):1575–1577
Strnad P, Rob L, Halaska MG, Chod J, Zuntova A, Moravcova Z, 2006, Radioguided occult lesion localisation in combination with detection of the sentinel lymph node in non-palpable breast cancer tumours. Eur J Gynaecol Oncol 27(3):236–238
Moreno M, Wiltgen JE, Bodanese B, Schmitt RL, Gutfilen B, da Fonseca LM, 2008, Radioguided breast surgery for occult lesion localisation—correlation between two methods. J Exp Clin Cancer Res 15(27):29
Mariscal Martinez A, Sola M, de Tudela AP, Julian JF, Fraile M, Vizcaya S et al, 2009, Radioguided localisation of nonpalpable breast cancer lesions: randomized comparison with wire localisation in patients undergoing conservative surgery and sentinel node biopsy. AJR Am J Roentgenol 193(4):1001–1009
Lovrics PJ, Cornacchi SD, Vora R, Goldsmith CH, Kahnamoui K, 2011, Systematic review of radioguided surgery for non-palpable breast cancer. Eur J Surg Oncol 37(5):388–397
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Besic N, Zgajnar J, Hocevar M, Rener M, Frkovic-Grazio S, Snoj N et al, 2002, Breast biopsy with wire localisation: factors influencing complete excision of nonpalpable carcinoma. Eur Radiol 12, 11):2684–2689
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 267
EP 273
DI 10.1007/s12253-012-9578-9
PG 7
ER
PT J
AU Shen, Y
Liu, Y
Liu, Sh
Zhang, A
AF Shen, Yizhen
Liu, Yi
Liu, Shaoge
Zhang, Aimin
TI Toll-like Receptor 4 Gene Polymorphisms and Susceptibility to Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Toll-like receptor 4; Polymorphism; Bladder cancer
ID Toll-like receptor 4; Polymorphism; Bladder cancer
AB Bladder cancer is one of the most common malignancies in the world. Toll-like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with bladder cancer. Four TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Il3, and +3725G/C) were genotyped in a total number of 436 bladder cancer patients and 522 healthy controls. Data were analyzed using the Chi-square test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in bladder cancer cases than in controls (odds ratio [OR]01.58, 95 % confidence interval [CI]01.19–2.10, p0 0.0015, and OR02.33, 95%CI01.52–3.58, p<0.0001, respectively). Also, the frequency of TLR4 +3725C allele was significantly higher in bladder cancer patients (p<0.0001). The -2242T/C, Asp299Gly and Thr399Il3 polymorphisms did not reveal any significant differences between cases and controls. Stratification analysis of the clinical features in the patients demonstrated that cases with invasive cancer were correlated with higher numbers of +3725GC and CC genotype (p<0.0004 and p<0.0231). In conclusion, these results indicate that TLR4 +3725G/C polymorphism may be a novel risk factor for bladder cancer in the Chinese population.
C1 [Shen, Yizhen] General Hospital of Jinan Military Command, Department of Urology, 25 Shifan Road, 250031 Jinan, Shandong, China.
[Liu, Yi] General Hospital of Jinan Military Command, Department of Urology, 25 Shifan Road, 250031 Jinan, Shandong, China.
[Liu, Shaoge] General Hospital of Jinan Military Command, Department of Urology, 25 Shifan Road, 250031 Jinan, Shandong, China.
[Zhang, Aimin] General Hospital of Jinan Military Command, Department of Urology, 25 Shifan Road, 250031 Jinan, Shandong, China.
RP Zhang, A (reprint author), General Hospital of Jinan Military Command, Department of Urology, 250031 Jinan, China.
EM zhangiaimin@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 275
EP 280
DI 10.1007/s12253-012-9579-8
PG 6
ER
PT J
AU Miao, Y
Li, AL
Wang, L
Fan, ChF
Zhang, XP
Xu, HT
Yang, LH
Liu, Y
Wang, EH
AF Miao, Yuan
Li, Ai-Lin
Wang, Liang
Fan, Chui-Feng
Zhang, Xiu-Peng
Xu, Hong-Tao
Yang, Lian-He
Liu, Yang
Wang, En-Hua
TI Overexpression of NEDD9 is Associated with Altered Expression of E-Cadherin, β-Catenin and N-Cadherin and Predictive of Poor Prognosis in non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; NEDD9; Epithelial-mesenchymal transition; Lymphatic metastasis; Prognosis
ID Non-small cell lung cancer; NEDD9; Epithelial-mesenchymal transition; Lymphatic metastasis; Prognosis
AB Neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) is overexpressed in multiple tumor types, where it is thought to regulate tumor cell metastasis and act as a trigger of the epithelial-mesenchymal transition (EMT). Loss of E-cadherin/β-catenin and upregulation of Ncadherin are hallmarks of the EMT. The expression and correlation of NEDD9 with E-cadherin, β-catenin and Ncadherin in lung cancer are poorly characterized. We examined NEDD9, E-cadherin, β-catenin and N-cadherin protein expression in 105 cases of non-small cell lung carcinoma (NSCLC), including 43 cases of squamous cell carcinoma and 62 cases of lung adenocarcinoma, and the corresponding normal lung tissues using immunohistochemistry. NEDD9 was overexpressed in 56.2% (59/105) of the NSCLC samples compared to normal lung tissue. Overexpression of NEDD9 correlated with abnormal expression of E-cadherin, β-catenin and N-cadherin (P<0.001, P<0.008 and P<0.027, respectively). Additionally, overexpression of NEDD9 correlated positively with lymph node metastasis in NSCLC (Chisquare test; P<0.015). The mean overall survival of NSCLC patients overexpressing NEDD9 (39.10±6.49 months) was markedly shorter than patients with normal NEDD9 expression (56.67±7.44 months; Log-Rank, P<0.001). Moreover, for patients with adenocarcinoma or squarmous cell carcinoma, the survival is also dramatically poorer upon overexpression of NEDD9. In multivariate analysis, overexpression of NEDD9 (P<0.013) and TNM stage (P<0.001) were significant independent prognostic factors for overall survival in NSCLC. In conclusion, overexpression of NEDD9 correlates with altered expression of EMT markers, increased lymph node metastasis and poorer survival in lung cancer.
C1 [Miao, Yuan] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Li, Ai-Lin] the First Affiliated Hospital of China Medical University, Department of RadiotherapyShenyang, China.
[Wang, Liang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Fan, Chui-Feng] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Zhang, Xiu-Peng] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Xu, Hong-Tao] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Yang, Lian-He] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Liu, Yang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
[Wang, En-Hua] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, China.
RP Wang, EH (reprint author), China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, Shenyang, China.
EM wangeh@hotmail.com
CR Travis WD, 2011, Pathology of lung cancer. Clin Chest Med 32, 4):669–692
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 281
EP 286
DI 10.1007/s12253-012-9580-2
PG 6
ER
PT J
AU Sulfikkarali, N
Krishnakumar, N
Manoharan, Sh
Nirmal, MR
AF Sulfikkarali, Nechikkad
Krishnakumar, Narendran
Manoharan, Shanmugam
Nirmal, Madhavan Ramadas
TI Chemopreventive Efficacy of Naringenin-Loaded Nanoparticles in 7,12-dimethylbenz(a)anthracene Induced Experimental Oral Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nanochemoprevention; DMBA; Hamster buccal pouch carcinogenesis; Naringenin
ID Nanochemoprevention; DMBA; Hamster buccal pouch carcinogenesis; Naringenin
AB Nanochemoprevention has been introduced recently as a novel approach for improving phytochemicals bioavailability and anti-tumor effect. The present study is designed to evaluate the chemopreventive efficacy of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of lipid peroxidation, antioxidants and immunoexpression patterns of proliferating cell nuclear antigen (PCNA) and p53 proteins. Transmission electron microscope (TEM) and dynamic light scattering (DLS) investigations have confirmed a narrow size distribution of the prepared nanoparticles (40–90 nm) with ~88 % encapsulation efficiency. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA in liquid paraffin three times a week for 14 weeks. DMBA painted animals revealed the morphological changes, hyperplasia, dysplasia and welldifferentiated squamous cell carcinoma. Moreover, the status of lipid peroxidation, antioxidants and immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of NARNPs (50 mg NAR/kg body weight/day) to DMBA-treated animals completely prevented the tumor formation as compared to the free NAR and significantly reduced the degree of histological lesions, in addition to restoration of the status of biochemical and molecular markers during oral carcinogenesis. In addition, NARNPs have more potent anti-lipid peroxidative, antiproliferative effect and antioxidant potentials compared to free NAR in DMBA-induced oral carcinogenesis. In conclusion, the present study suggests that NARNPs could be a potentially useful drug carrier system for targeted delivery of naringenin for cancer chemoprevention.
C1 [Sulfikkarali, Nechikkad] Annamalai University, Department of Physics, 608 002 Annamalainagar, Tamilnadu, India.
[Krishnakumar, Narendran] Annamalai University, Department of Physics, 608 002 Annamalainagar, Tamilnadu, India.
[Manoharan, Shanmugam] Annamalai University, Department of Biochemistry and Biotechnology, 608 002 Annamalainagar, Tamilnadu, India.
[Nirmal, Madhavan Ramadas] Annamalai University, Rajah Muthiah Dental College & Hospital, Department of Oral and Maxillofacial Pathology, 608 002 Annamalainagar, Tamilnadu, India.
RP Krishnakumar, N (reprint author), Annamalai University, Department of Physics, 608 002 Annamalainagar, India.
EM nskumarphyamu@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 287
EP 296
DI 10.1007/s12253-012-9581-1
PG 10
ER
PT J
AU Nyari, AT
Ottoffy, G
Bartyik, K
Thurzo, L
Solymosi, N
Cserni, G
Parker, L
McNally, JQR
AF Nyari, Andras Tibor
Ottoffy, Gabor
Bartyik, Katalin
Thurzo, Laszlo
Solymosi, Norbert
Cserni, Gabor
Parker, Louise
McNally, J Q Richard
TI Spatial Clustering of Childhood Acute Lymphoblastic Leukaemia in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute lymphoblastic leukaemia; Aetiology; Childhood; Cluster analysis; Environmental exposure; Spatial distribution; Gender specific effect; Male predominance
ID Acute lymphoblastic leukaemia; Aetiology; Childhood; Cluster analysis; Environmental exposure; Spatial distribution; Gender specific effect; Male predominance
AB The aetiology of childhood acute lymphoblastic leukaemia has been linked with spatially heterogeneous environmental exposures. The presence of spatial clustering would be consistent with geographically localized environmental exposures over long periods of time. The present study is the first to examine spatial clustering amongst children aged 0– 4 years using population-based data from Hungary. The data set consisted of 134 children diagnosed with acute lymphoblastic leukaemia who were resident in part of Hungary during the period 1981–2000. Two levels of spatial aggregation were examined: counties and settlements. The Potthoff-Whittinghill and Moran I autocorrelation methods were used to test for spatial clustering. Additionally, an evaluation of the environmental changes during the study period was considered. Specifically analyses were carried out on sub-periods to investigate a possible effect of the Chernobyl catastrophe. There was statistically significant spatial clustering both at the county (estimate of extra-Poisson variation (β)=0.56, P=0.04) and settlement levels (estimate of extra-Poisson variation (β)=0.68, P=0.0003). At county level, the finding was attributable to clustering amongst female cases, but at settlement level, the finding was limited to male cases. There was significant spatial autocorrelation in the sub-periods immediately following the accident (1986–1990 & 1991–1995), but not before 1986, nor after 1995. A significant autocorrelation was observed during the 5 year period immediately following the accident (1986–1990, global Moran I=0.1334, p=0.005). The centre of significant excesses of ALL cases was located in the county of Baranya. Our study is consistent with an environmental aetiology for acute lymphoblastic leukaemia in children associated with constant exposure to an, as yet unknown, environmental factor in small geographical areas. Although a possible effect of the Chernobyl accident was found in the autocorrelation analysis, the role of chance cannot be excluded.
C1 [Nyari, Andras Tibor] University of Szeged, Department of Medical Informatics, 6701 Szeged, Hungary.
[Ottoffy, Gabor] University of Pecs, Department of PediatricsPecs, Hungary.
[Bartyik, Katalin] University of Szeged, Department of PediatricsSzeged, Hungary.
[Thurzo, Laszlo] University of Szeged, Department of OncotherapySzeged, Hungary.
[Solymosi, Norbert] Saint Stephen University Budapest, Department of Animal Hygiene, Herd-health and Veterinary EtiologyBudapest, Hungary.
[Cserni, Gabor] University of Szeged, Department of PathologySzeged, Hungary.
[Parker, Louise] Dalhousie University, IWK Health Centre, Department of PediatricsHalifax, Canada.
[McNally, J Q Richard] Newcastle University, Institute of Health and SocietyNewcastle upon Tyne, UK.
RP Nyari, AT (reprint author), University of Szeged, Department of Medical Informatics, 6701 Szeged, Hungary.
EM Nyari.Tibor@med.u-szeged.hu
CR McNally RJQ, Eden TOB, 2004, An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol 127:243–263
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 297
EP 302
DI 10.1007/s12253-012-9582-0
PG 6
ER
PT J
AU Zhou, P
Wu, LL
Wu, KM
Jiang, W
Li, Jd
Zhou, Ld
Li, XY
Chang, Sh
Huang, Y
Tan, H
Zhang, GW
He, F
Wang, ZM
AF Zhou, Peng
Wu, Lie-Lin
Wu, Ke-Min
Jiang, Wei
Li, Jin-dong
Zhou, Le-du
Li, Xin-Ying
Chang, Shi
Huang, Yun
Tan, Hui
Zhang, Ge-Wen
He, Feng
Wang, Zhi-Ming
TI Overexpression of MMSET is Correlation with Poor Prognosis in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; MMSET; Clinicopathology; Prognosis; Disease-free survival; Overall survival
ID Hepatocellular carcinoma; MMSET; Clinicopathology; Prognosis; Disease-free survival; Overall survival
AB The multiple myeloma SET domain (MMSET) involved in the t(4;14)(p16;q32) chromosomal translocation encodes a histone lysine methyltransferase. High expression of MMSET is common translocation in multiple myeloma (MM) and is associated with the worst prognosis. Recent studies have shown that overexpression of MMSET is significant in other tumor types compared to their normal tissues. However, little is known about its role in hepatocellular carcinoma (HCC). In these study we investigate the expression of MMSET in HCC and to make correlations with clinicopathologic features. Twenty-eight pairs of HCC and adjacent non-tumor tissues, and eight normal liver tissues were collected for MMSET detection by western blotting and real time-PCR analysis. Immunohistochemistry was used to determine the expression of MMSET in HCC and adjacent non-tumor tissues from 103 patients. Overexpression of MMSET was significantly associated with Edmondson stage, vascular invasion. Moreover, Kaplan- Meier curves showed that MMSET upregulated was associated with shorter overall survival and disease-free survival in HCC patient. In conclusion, our study demonstrates for the first time that overexpression of MMSET is an independent prognostic factor and is correlated with poor survival in HCC patients.
C1 [Zhou, Peng] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Wu, Lie-Lin] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Wu, Ke-Min] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Jiang, Wei] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Li, Jin-dong] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Zhou, Le-du] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Li, Xin-Ying] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Chang, Shi] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Huang, Yun] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Tan, Hui] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Zhang, Ge-Wen] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[He, Feng] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
[Wang, Zhi-Ming] Central South University, Xiangya Hospital, Department of General Surgery, No.87 Xiangya Road, 410008 Changsha, China.
RP Wang, ZM (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
EM wzm005@yahoo.com.cn
CR Di Bisceglie AM, 2004, Issues in screening and surveillance for hepatocellular carcinoma. Gastroenterology 127:S104–S107
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 303
EP 309
DI 10.1007/s12253-012-9583-z
PG 7
ER
PT J
AU Cui, J
Xu, G
Liu, J
Pang, Z
Florholmen, J
Cui, G
AF Cui, Jing
Xu, Gang
Liu, Jinzhong
Pang, Zhigang
Florholmen, Jon
Cui, Guanglin
TI The Expression of Non-Mast Histamine in Tumor Associated Microvessels in Human Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Histamine; Angiogenesis; Colorectal cancer
ID Histamine; Angiogenesis; Colorectal cancer
AB Angiogenesis is essential for the growth, expansion and metastasis of human colorectal cancers (CRCs). Histamine produced by mast cells is a potent proangiogenic factor. However, the significance of non-mast cell expressing histamine in the tumor microenvironment remains unknown. In this study, we evaluated the histamine positive microvessels with the specific marker for biosynthesis of histamine L-histidine decarboxylase (HDC) in the CRC tumor microenvironment. The relationship between HDC positive microvessel density (HDC-MVD) and clinical pathological parameters was assessed. The results revealed that HDC-MVD in the tumor microenvironment of CRCs was significantly increased as compared with the controls. CRC patients with lymph node invasion had a particularly higher density of HDC-MVD than those without. The density of HDC-MVD accounted for ~79 % of CD34 positive MVD in CRCs and double IHC analysis demonstrated that these HDC positive microvessels were mostly CD34 positive microvessels and with a high proliferative activity. Our results suggest that histamine expressed in microvessels could be an additional cellular source and involved in the cancer invasion through promoting angiogenesis in human CRCs.
C1 [Cui, Jing] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
[Xu, Gang] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
[Liu, Jinzhong] the Fourth Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, Henan, China.
[Pang, Zhigang] the Second Affiliated Hospital of Zhengzhou University, Department of Gastrointestinal SurgeryZhengzhou, Henan, China.
[Florholmen, Jon] University of Tromso, Faculty of Medicine, Institute of Clinical Medicine, Laboratory of Gastroenterology & NutritionTromso, Norway.
[Cui, Guanglin] the Second Affiliated Hospital of Zhengzhou University, Department of MedicineZhengzhou, Henan, China.
RP Cui, G (reprint author), the Second Affiliated Hospital of Zhengzhou University, Department of Medicine, Zhengzhou, China.
EM guanglin.cui@uit.no
CR Timar J, Csuka O, Orosz Z, Jeney A, Kopper L, 2001, Molecular pathology of tumor metastasis. I. Predictive pathology. Pathol Oncol Res POR 7:217–230
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Hellstrand K, Brune M, Naredi P, Mellqvist UH, Hansson M et al, 2000, Histamine: a novel approach to cancer immunotherapy. Cancer Investig 18:347–355
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 311
EP 316
DI 10.1007/s12253-012-9584-y
PG 6
ER
PT J
AU Zizhen, Z
Hui, C
Yanying, Sh
Danping, Sh
Jiahua, L
Chao, H
Xingzhi, N
AF Zizhen, Zhang
Hui, Cao
Yanying, Shen
Danping, Shen
Jiahua, Liu
Chao, He
Xingzhi, Ni
TI Correlation Between Immunophenotype Classification and Clinicopathological Features in Chinese Patients with Primary Gastric Diffuse Large B-Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diffuse large B-cell lymphoma; Immunophenotype; Primary gastric lymphoma; Prognosis
ID Diffuse large B-cell lymphoma; Immunophenotype; Primary gastric lymphoma; Prognosis
AB Recent studies have shown that diffuse large Bcell lymphoma (DLBCL) can be classified into germinal center B-cell–like (GCB) and non-GCB phenotypes by immunohistochemical staining. The aim of this study was to investigate the correlation of immunophenotypic classification with clinicopathological features in Chinese patients with primary gastric DLBCL to further our knowledge of this disease. Seventy-three patients with a histopathological diagnosis of primary gastric DLBCL were studied. Immunohistochemistry was carried out using the EnVision method to detect the expression of CD10, Bcl-6, and MUM1. The clinicopathologic features and follow-up data were analyzed using the Kaplan–Meier method, log-rank test, and χ2 test. Expression of CD10 was observed in 21.9 % (16/73) of patients, Bcl-6 in 72.6 % (53/73), and MUM1 in 74.0 % (54/73). According to these data, 32.9 % (24/73) of the cases belonged to GCB subtype and 67.1 % (49/73) belonged to non-GCB subtype. There was a significant difference in tumor size and local lymph node metastasis between the GCB and non-GCB groups (P<0.05). Complications in the GCB group (4.2 %) occurred less frequently than those in the non-GCB group (18.4 %); however, this difference was not significant (P>0.05). Survival analysis revealed that patients in the GCB group had an increased 5- year survival rate compared to those in the non-GCB group (58.5 % vs 35.7 %, χ2=3.939, P<0.05). The 5-year survival rate of patients undergoing R-CHOP chemotherapy was significantly longer than that of patients in the CHOP group (74.7 % vs 37.5 %, χ2=4.185, P<0.05). The immunophenotype classification of primary gastric DLBCL, which is closely related to the tumor size and local lymph nodes metastasis, was found to have prognostic significance.
C1 [Zizhen, Zhang] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
[Hui, Cao] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
[Yanying, Shen] Medical College of Shanghai Jiao Tong University, Ren Ji Hospital, Department of Pathology, Dongfang Road 1630, 200127 Shanghai, China.
[Danping, Shen] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
[Jiahua, Liu] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
[Chao, He] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
[Xingzhi, Ni] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, Dongfang Road 1630, 200127 Shanghai, China.
RP Xingzhi, N (reprint author), Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, 200127 Shanghai, China.
EM zzzhang16@hotmail.com
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Berglund M, Thunberg U, Amini RM, Book M, Roos G, Erlanson M, Linderoth J, Dictor M, Jerkeman M, Cavallin-Stahl E, Sundstrom C, Rehn-Eriksson S, Backlin C, Hagberg H, Rosenquist R, Enblad G, 2005, Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. Mod Pathol 18:1113–1120
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Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, Braziel RM, Geng H, Iqbal J, Lenz G, Vose JM, Hans CP, Fu K, Smith LM, Li M, Liu Z, Gascoyne RD, Rosenwald A, Ott G, Rimsza LM, Campo E, Jaffe ES, Jaye DL, Staudt LM, Chan WC, 2009, A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 15:5494–5502
Meyer PN, Fu K, Greiner TC, Smith LM, Delabie J, Gascoyne RD,Ott G, Rosenwald A, Braziel RM, Campo E, Vose JM, Lenz G, Staudt LM, Chan WC, Weisenburger DD, 2010, Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with Rituximab. J Clin Oncol 29:200–207
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C, 2002, CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242
Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ, 2006, Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large Bcell lymphoma. J Clin Oncol 24:3121–3127
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Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, Hans CP, Greiner TC, Bierman PJ, Bociek RG, Armitage JO, Chan WC, Vose JM, 2008, Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-celllike and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol 26:4587–4594
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 317
EP 322
DI 10.1007/s12253-012-9585-x
PG 6
ER
PT J
AU Toth, V
Somlai, B
Hatvani, Zs
Szakonyi, J
Gaudi, I
Karpati, S
AF Toth, Veronika
Somlai, Beata
Hatvani, Zsofia
Szakonyi, Jozsef
Gaudi, Istvan
Karpati, Sarolta
TI Melanoma Screening in a Hungarian Nuclear Power Plant
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sun exposure; Hazard of ionizing radiation; Nuclear power plant; Melanoma screening; Melanoma incidence
ID Sun exposure; Hazard of ionizing radiation; Nuclear power plant; Melanoma screening; Melanoma incidence
AB The industrial use of the ionizing radiation (IR) particularly stresses the safe work, regular health control is inevitable. Since previous occupational cohorts reported contradictory data on the incidence of melanoma among nuclear industry workers, and in few publications significant increase of it has been described, our clinic was requested by the industry to screen malignant skin tumours among the workers of a power plant. Within a year we have investigated 556 workers, 275 females and 281 males. Out of them 283, majorly males had been officially confirmed as to be employed at hazardous, but strictly controlled environment for an average of 18 years (1–32 years). To distinguish between IR and environmental UV (UVA+UVB) induced cutaneous malignancies we determined the sun and tanning bed exposure of the workers. One in situ melanoma developed in a woman with type I skin, bullous sunburns in the history, who had worked in safe environment for 26 years. Basal cell carcinoma was identified in two men, each of them worked for more than 20 years with IR (in hazardous environment). One had type I skin, the other had type II skin. These results didn’t differ significantly (chi-squared test; p00, 2437 and 1, 0) from the national population data and the results of Euromelanoma screening campaign in Hungary. Our data clearly show, that 1./UV exposure and skin type should be evaluated in occupation cohort studies. 2./The melanoma incidence was not significantly higher among the employees of the power plant than in the general Hungarian population, according to the results of our study, the only Hungarian power plant is safe as far as the skin carcinogenesis is concerned.
C1 [Toth, Veronika] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Hatvani, Zsofia] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Szakonyi, Jozsef] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Gaudi, Istvan] National Institute of Oncology, Rath Gyorgy street 7-9, 1122 Budapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
RP Toth, V (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM toveroka@yahoo.com
CR Austin DF, Reynolds PJ, Snyder MA, Biggs MW, Stubbs HA, 1981, Malignant melanoma among employees of Lawrence Livermore National Laboratory. Lancet 2:712–716
Acquavella JF,Wilkinson GS, Tietjen GL, Key CR, Voelz GL, 1982, Malignant melanoma incidence at the Los Alamos National Laboratory. Lancet 319:883–884
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Smith PG, Douglas AJ, 1986, Mortality of workers at the Sellafield plant of British Nuclear Fuels. Br Med J 293:845–854
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Moore DH 2nd, Patterson HW, Hatch F, Discher D, Schneider JS, Bennett D et al, 1997, Case–controll study of malignant melanoma among employees of the Lawrence Livermore National Laboratory. Am J Ind Med 32:377–391
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Gawkrodger DJ, 2004, Occupational skin cancers. Occup Med 54:458–463
Gaudi I, Kasler M, 2003, New cases of melanoma as documented in the National Cancer Registry. Hungarian Oncology 47:13–17
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 323
EP 328
DI 10.1007/s12253-012-9587-8
PG 6
ER
PT J
AU Televantou, D
Karkavelas, G
Hytiroglou, P
Lampaki, S
Iliadis, G
Selviaridis, P
Polyzoidis, SK
Fountzilas, G
Kotoula, V
AF Televantou, Despina
Karkavelas, George
Hytiroglou, Prodromos
Lampaki, Sofia
Iliadis, George
Selviaridis, Panagiotis
Polyzoidis, S Konstantinos
Fountzilas, George
Kotoula, Vassiliki
TI DARPP32, STAT5 and STAT3 mRNA Expression Ratios in Glioblastomas are Associated with Patient Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma subtyping; IDH-negative disease; DARPP32; STAT3; STAT5A; STAT5B; Geneexpression; Survivin
ID Glioblastoma subtyping; IDH-negative disease; DARPP32; STAT3; STAT5A; STAT5B; Geneexpression; Survivin
AB Based on recent developments in glioblastoma subtyping, we examined DARPP32 (PPP1R1B), a neuronal marker against STAT5 and STAT3 that are pro-oncogenic in glioblastoma. mRNA ratios of DARPP32, STAT1, STAT3, STAT5A and STAT5B were assessed in routinely diagnosed gliomas s including a series of glioblastomas from patients (n067) treated with chemoradiotherapy (temozolomide), out of which 88 % had sequencing validated IDH-negative disease. DARPP32/STAT1 (p00.0007), DARPP32/STAT3 (p0 0.0004) and DARPP32/STAT5B (p00.0039) ratios were significantly higher in grade II and III as compared to grade IV tumours. The same high ratios were also associated with absence of immunohistochemically assessed AKT/PKB phosphorylation and survivin protein expression. High DARPP32/ STAT3,DARPP32/STAT5B, and STAT5B/STAT3 ratios were associated with longer patient progression free (PFS) and overall survival (OS). Upon multivariate analysis, total/subtotal removal of the tumour (HR:0.431; 95%CI:0.241–0.771, Wald p00.005), high DARPP32/STAT5B (HR:0.341; 95%CI:0.169–0.690; Wald p00.003) and STAT5B/STAT3 mRNA ratios (HR:0.480; 95%CI:0.280–0.824; Wald p0 0.008) were independent favorable parameters for prolonged PFS. Extent of surgery (HR:0.198; 95%CI:0.101–0.390; p< 0.001) and high DARPP32/STAT5A ratios (HR:0.320; 95%CI:0.160–0.638, p00.001) were independently predictive for longer OS. The presented approach is applicable for prospective validation and appears promising towards an effective glioblastoma patient stratification in addition to IDH mutations. These data may contribute to understanding the biology of gliomas with respect to their potential neuronal characteristics and justify STAT-inhibiting therapeutic interventions in the same tumour system.
C1 [Televantou, Despina] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology Department, 54006 Thessaloniki, Greece.
[Karkavelas, George] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology Department, 54006 Thessaloniki, Greece.
[Hytiroglou, Prodromos] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology Department, 54006 Thessaloniki, Greece.
[Lampaki, Sofia] Aristotle University of Thessaloniki School of Medicine, Department of Medical OncologyThessaloniki, Greece.
[Iliadis, George] Department of Radiation OncologyThessaloniki, Greece.
[Selviaridis, Panagiotis] Aristotle University of Thessaloniki, AHEPA Hospital, 1st Neurosurgical DepartmentThessaloniki, Greece.
[Polyzoidis, S Konstantinos] Aristotle University of Thessaloniki, AHEPA Hospital, 1st Neurosurgical DepartmentThessaloniki, Greece.
[Fountzilas, George] Aristotle University of Thessaloniki School of Medicine, Department of Medical OncologyThessaloniki, Greece.
[Kotoula, Vassiliki] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology Department, 54006 Thessaloniki, Greece.
RP Kotoula, V (reprint author), Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology Department, 54006 Thessaloniki, Greece.
EM vkotoula@auth.gr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2013
VL 19
IS 2
BP 329
EP 343
DI 10.1007/s12253-012-9588-7
PG 15
ER
PT J
AU Muzes, Gy
Sipos, F
Csomor, J
Sreter, L
AF Muzes, Gyorgyi
Sipos, Ferenc
Csomor, Judit
Sreter, Lidia
TI Multicentric Castleman’s Disease: A Challenging Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Multicentric Castleman’s disease; HHV-8; IL-6; Differential diagnosis; Therapy; Monoclonal antibodies
ID Multicentric Castleman’s disease; HHV-8; IL-6; Differential diagnosis; Therapy; Monoclonal antibodies
AB Multicentric Castleman’s disease (MCD) is a sytemic disorder with flares of non-specific symptoms suggestive of a chronic inflammatory syndrome. It is typically accompanied by generalized lymphadenopathy and multiorgan involvement. Histologically, two main variants of Castleman’s disease exist, the hyalin vascular type and the plasma cell variant. Upon localization unicentric (localized), and multicentric (diffuse, systemic) subtypes can be distinguished with more different disease outcomes. Patients often exhibit acute phase reactions and several autoimmune phenomena, and are at high risk for developing malignancies. Both the idiopathic and the HHV-8-driven infectious forms of MCD represent distinct disease entities with a less favorable prognosis. The induction of human IL-6 excess via yet unknown upstream mechanisms, and overexpression of viral IL-6 by HHV-8 can pivotally influence MCD biology. Based on the role of IL-6 in pathogenesis, MCD is also designated as IL-6 lymphadenopathy. To date there are no direct therapeutic evidences, but having been translated to daily practice the main regulatory factors may serve as promising therapeutic targets.
C1 [Muzes, Gyorgyi] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1088 Budapest, Hungary.
[Sreter, Lidia] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary.
RP Muzes, Gy (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM muzes.gyorgyi@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 345
EP 351
DI 10.1007/s12253-013-9619-z
PG 7
ER
PT J
AU Turi, K
Barabas, P
Csurgay, K
Lehner, Gy
Lorincz,
Nemeth, Zs
AF Turi, Katalin
Barabas, Peter
Csurgay, Katalin
Lehner, Gyorgy
Lorincz, Adam
Nemeth, Zsolt
TI An Analysis of the Epidemiological and Etiological Factors of Oral Tumors of Young Adults in a Central-Eastern European Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Young adult; Oral cancer; Epidemiology; Etiology; Human papilloma virus
ID Young adult; Oral cancer; Epidemiology; Etiology; Human papilloma virus
AB The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV-associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.
C1 [Turi, Katalin] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
[Barabas, Peter] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
[Csurgay, Katalin] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
[Lehner, Gyorgy] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
[Lorincz, Adam] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
[Nemeth, Zsolt] Semmelweis University, Department of Oral and Maxillofacial Surgery, Maria str. 52, 1085 Budapest, Hungary.
RP Nemeth, Zs (reprint author), Semmelweis University, Department of Oral and Maxillofacial Surgery, 1085 Budapest, Hungary.
EM nemeth.zsolt@dent.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 353
EP 363
DI 10.1007/s12253-013-9628-y
PG 11
ER
PT J
AU Pecina-Slaus, N
AF Pecina-Slaus, Nives
TI Merlin, the NF2 Gene Product
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NF2 gene; Merlin; Schwannoma; Neurinoma
ID NF2 gene; Merlin; Schwannoma; Neurinoma
AB Merlin, the protein product of NF2 gene, is one of the most versatile tumor suppressors capable of integrating different mechanisms that regulate cell proliferation, motility, survival and signaling pathways underlying and governing those mechanisms. Merlin is considered a member of the band 4.1 families of cytoskeleton-associated proteins also called ERM family and acts as tumor suppressor. The main cause for transformation of Schwann cells into schwannomas is credited to the inactivation of the neurofibromin 2 (NF2) gene and the consecutive loss of its protein merlin. Recent scientific advances improved our understanding of pathogenic mechanisms involving NF2 gene. The present review brings genetic properties of NF2 gene, molecular characteristics of merlin, summarizes mutational spectra and explains merlin’s multifunctional roles regarding its involvement in neurofibromatosis associated tumorigenesis.
C1 [Pecina-Slaus, Nives] University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Laboratory of Neurooncology, Salata 12, 10000 Zagreb, Croatia.
RP Pecina-Slaus, N (reprint author), University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Laboratory of Neurooncology, 10000 Zagreb, Croatia.
EM nina@mef.hr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 365
EP 373
DI 10.1007/s12253-013-9644-y
PG 9
ER
PT J
AU Jenei, Z
Bardi, E
Magyar, TM
Horvath,
Paragh, Gy
Kiss, Cs
AF Jenei, Zoltan
Bardi, Edit
Magyar, Tunde Maria
Horvath, Agnes
Paragh, Gyorgy
Kiss, Csongor
TI Anthracycline Causes Impaired Vascular Endothelial Function and Aortic Stiffness in Long Term Survivors of Childhood Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Childhood cancer; Survivors; Endothelial dysfunction; Stiffness
ID Childhood cancer; Survivors; Endothelial dysfunction; Stiffness
AB Vascular and endothelial functions were investigated in long term survivors of childhood cancer exposed to anthracycline treatment. We enrolled 96 long-term survivors (57 males and 39 females, mean age 14.9±5.3 year) of different childhood cancers and 72 age-, sex-, bodyweightand blood pressure matched controls (39 males and 33 females, mean age 13.7±4.9 year). Aortic stiffness was characterized by echocardiography. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD%) and nitrate-mediated dilatation (NTG%). Results were compared between three subgroups: anthracycline treated, only chemotherapy treated and control subgroups. The cumulative anthracycline dose was less than 350 mg/ m2. The healthy control subgroup had a significantly greater FMD response (13.13±2.40 %), and lower stiffness index (2.08±0.6) than both the anthracycline (7.12±6.28 % and 6.45±3.25, respectively) and only chemotherapy treated (10.17±4.23 % and 4.12±2.32, respectively) subgroups. In the anthracycline treated subgroup a significantly (p<0.01) lower FMD% response, and higher stiffness index were detected than in the only chemotherapy treated subgroup. Higher triglyceride level, higher cumulative anthracycline dose and lower age at the start of treatment were found to be associated independently with impairment of FMD% response and aortic stiffness. We found a significant negative correlation between FMD and aortic stiffness (p<0.001) and a positive correlation between FMD and distensibility (p<0.0001) Childhood cancer long term survivors exposed to anthracycline treatment exhibit a marked preclinical vasculopathy, characterized by endothelial dysfunction and increased arterial stiffness, contributing to a deteriorated cardiovascular function.
C1 [Jenei, Zoltan] University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Nagyerdei krt. 98, 4025 Debrecen, Hungary.
[Bardi, Edit] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Magyar, Tunde Maria] University of Debrecen, Medical and Health Science Center, Department of NeurologyDebrecen, Hungary.
[Horvath, Agnes] University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Nagyerdei krt. 98, 4025 Debrecen, Hungary.
[Paragh, Gyorgy] University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Nagyerdei krt. 98, 4025 Debrecen, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
RP Jenei, Z (reprint author), University of Debrecen, Faculty of Medicine, Department of Internal Medicine, 4025 Debrecen, Hungary.
EM jenei@internal.med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 375
EP 383
DI 10.1007/s12253-012-9589-6
PG 9
ER
PT J
AU Yahyapour, Y
Shamsi-Shahrabadi, M
Mahmoudi, M
Motevallian, A
Siadati, S
Shefaii, S
Shirvani, ShJ
Mollaie, H
Monavari, HRS
Keyvani, H
AF Yahyapour, Yousef
Shamsi-Shahrabadi, Mahmoud
Mahmoudi, Mahdi
Motevallian, Abbas
Siadati, Sepideh
Shefaii, S
Shirvani, Shokri Javad
Mollaie, R. Hamidreza
Monavari, Hamid Reza Seyed
Keyvani, Hossein
TI High-Risk and Low-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma at Mazandaran, Northern Iran
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE High-risk and Low-risk HPV; Genotyping; ESCC; Mazandaran; North of Iran
ID High-risk and Low-risk HPV; Genotyping; ESCC; Mazandaran; North of Iran
AB Cancers are the second most common cause of nonaccidental deaths in Iran, following cardiovascular deaths. Mazandaran, near the Caspian Littoral at north of Iran have identified as a several-high incidence area for Esophageal Squamous Cell Carcinoma (ESCC) in the world. Several associated risk factors, such as dietary and cultural habits, infectious agents, nutritional deficiencies, too much use of tobacco and alcohol and infection to certain DNA tumor viruses (HPVs), including environmental and genetic factors are attributed to this disease. To explore this issue, we analyzed HPV DNA prevalence and HPV types together in relation to tumor sites a high-incidence population. Archived tissue blocks from 46, 69 and 62 upper, middle and lower third of esophagus, respectively from ESCC patients were evaluated for the presence of HPV DNA by PCR using the degenerate HPV L1 consensus primer pairs MY09/MY11. The positive specimens were evaluated by Real-time PCR to determine HPV genotypes. From the 49 HPV positive cases, of ESCC patients, 5 (23.1%), 11 (55 %) and 9 (56.3 %) of upper, middle and lower third of ESCC specimens, respectively were positive by at least one high and one low-risk HPV genotypes. In general, HPV45 and HPV11 were the most common high- risk and low-risk HPV genotypes in HPV L1 positive cases, respectively, followed by HPV6, HPV52 and HPV39. Therefore, the high prevalence of HPV DNA in different anatomical sites of ESCC patients from the Mazandaran region in North of Iran provides more evidence for a role of HPV in this cancer.
C1 [Yahyapour, Yousef] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Shamsi-Shahrabadi, Mahmoud] Tehran University of Medical Sciences, Faculty of Medicine, Department of Virology and Antimicrobial Resistance Research CenterTehran, Iran.
[Mahmoudi, Mahdi] School of Public Health, Tehran University of Medical Sciences, Department of Epidemiology and BiostatisticsTehran, Iran.
[Motevallian, Abbas] School of Public Health, Tehran University of Medical Sciences, Department of Epidemiology and BiostatisticsTehran, Iran.
[Siadati, Sepideh] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Shefaii, S] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Shirvani, Shokri Javad] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Mollaie, R. Hamidreza] Tehran University of Medical Sciences, Faculty of Medicine, Department of Virology and Antimicrobial Resistance Research CenterTehran, Iran.
[Monavari, Hamid Reza Seyed] Tehran University of Medical Sciences, Faculty of Medicine, Department of Virology and Antimicrobial Resistance Research CenterTehran, Iran.
[Keyvani, Hossein] Tehran University of Medical Sciences, Faculty of Medicine, Department of Virology and Antimicrobial Resistance Research CenterTehran, Iran.
RP Monavari, HRS (reprint author), Tehran University of Medical Sciences, Faculty of Medicine, Department of Virology and Antimicrobial Resistance Research Center, Tehran, Iran.
EM hrmonavari@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 385
EP 391
DI 10.1007/s12253-012-9590-0
PG 7
ER
PT J
AU Je, ME
Yoo, JN
Lee, HS
AF Je, Mi Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Somatic Mutation of PARK2 Tumor Suppressor Gene is not Common in Common Solid Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PARK2; Tumor suppressor; Mutation; Cancers
ID PARK2; Tumor suppressor; Mutation; Cancers
AB Recent studies identified that PARK2 gene was a candidate tumor suppressor gene in colorectal cancers and glioblastomas. The aim of this study was identify whether PARK2 somatic mutation is present in other solid tumor as well. In this study, we analyzed the entire coding sequences of human PARK2 gene in gastric, colorectal, breast, lung and prostate carcinoma by single-strand conformation polymorphism (SSCP) and subsequent direct DNA sequencing. We found two missense mutations (p.Ser9Thr and p.Gly450Val) in colon carcinomas (4.3 %), which were not overlapped with the known PARK2 mutations. Our data suggest that somatic mutational events in PARK2 gene may be rare in colorectal, gastric, prostate, breast and lung carcinomas and may not play an important role in the development of these cancers.
C1 [Je, Mi Eun] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Cancer Research Institute, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Yoshii SR, Kishi C, Ishihara N, Mizushima N, 2011, Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem 286:19630– 19640
Kahle PJ, Haass C, 2004, How does parkin ligate ubiquitin to Parkinson’s disease? EMBO Rep 5:681–685
Farrer MJ, 2006, Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7:306–318
Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A, 1999, A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson’s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Hum Mol Genet 8:567–574
Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, Trapasso F, Drusco A, Shimizu M, Masciullo V, D’Andrilli G, Scambia G, Picchio MC, Alder H, Godwin AK, Croce CM, 2003, Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci U S A 100:5956–5961
Picchio MC, Martin ES, Cesari R, Calin GA, Yendamuri S, Kuroki T, Pentimalli F, Sarti M, Yoder K, Kaiser LR, Fishel R, Croce CM, 2004, Alterations of the tumor suppressor gene Parkin in nonsmall cell lung cancer. Clin Cancer Res 10:2720–2724
Fujiwara M, Marusawa H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, Kataoka A, Nukina N, Takahashi R, Chiba T, 2008, Parkin as a tumor suppressor gene for hepatocellular carcinoma. Oncogene 27:6002–6011
Poulogiannis G, McIntyre RE, Dimitriadi M, Apps JR,Wilson CH, Ichimura K, Luo F, Cantley LC, Wyllie AH, Adams DJ, Arends MJ, 2010, PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc Natl Acad Sci U S A 107:15145–15150
Veeriah S, Taylor BS, Meng S, Fang F, Yilmaz E, Vivanco I, Janakiraman M, Schultz N, Hanrahan AJ, Pao W, Ladanyi M, Sander C, Heguy A, Holland EC, Paty PB, Mischel PS, Liau L, Cloughesy TF, Mellinghoff IK, Solit DB, Chan TA, 2010, Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet 42:77–82
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Kim MS, Hur SY, Yoo NJ, Lee SH, 2010, Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol 221:147–152
Kim MS, Oh JE, Kim YR, Park SW, Kang MR, Kim SS, Ahn CH, Yoo NJ, Lee SH, 2010, Somatic mutations and losses of expression of microRNA regulation-related genes AGO2 and TNRC6A in gastric and colorectal cancers. J Pathol 221:139–146
Kim YR, Oh JE, Kim MS, Kang MR, Park SW, Han JY, Eom HS, Yoo NJ, Lee SH, 2010, Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J Pathol 220:446–451
Hayashi K, 1992, PCR-SSCP: a simple and sensitive method for detection of mutations in the genomic DNA. PCR Methods Appl 1:34–38
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 393
EP 395
DI 10.1007/s12253-012-9591-z
PG 3
ER
PT J
AU Du, X
Zhao, H
Zang, L
Song, N
Yang, T
Dong, R
Yin, J
Wang, Ch
Lu, J
AF Du, Xilin
Zhao, Huadong
Zang, Li
Song, Nuan
Yang, Tao
Dong, Rui
Yin, Jikai
Wang, Chengguo
Lu, Jianguo
TI Overexpression of Histone Deacetylase 2 Predicts Unfavorable Prognosis in Human Gallbladder Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Primary gallbladder carcinoma; Histone deacetylase 2; Clinicopathology; Overall survival; Disease-free survival
ID Primary gallbladder carcinoma; Histone deacetylase 2; Clinicopathology; Overall survival; Disease-free survival
AB As important regulators of chromatin, histone deacetylases (HDACs) are involved in silencing tumor suppressor genes. HDAC2, a member of HDACs, has been demonstrated to be implicated in the development and progression of various human malignancies; however, its expression and role in human primary gallbladder carcinoma (PGC) are not fully understood. Therefore, we conducted this study to address this problem. The subjects were 136 patients underwent resection for PGC. Immunostainings for HDAC2 were performed on these archival tissues. The correlation of HDAC2 expression with clinicopathological characteristics including survival was analyzed. HDAC2 was positively expressed in the nucleus of tumor cells in 86.0 % (117/136) of PGC but not in the normal epithelium of the gallbladder. Additionally, there was a significant difference in the incidence of positive nodal metastasis between high and low HDAC2 expression groups (P00.001). The incidences of advanced clinical stage (P00.005) and pathologic T stage (P<0.001), and higher histologic grade (P<0.001) were respectively higher in the high HDAC2 expression group than in the low group. Moreover, univariate and multivariate analyses revealed the high HDAC2 expression to be an independent prognostic factor for both overall and disease-free survival of patients with PGC. High HDAC2 expression was correlated with a high incidence of lymph node metastasis and aggressive tumor progression of PGC. It also was an independent prognostic factor for poorer overall and disease-free survival in patients. Therefore, detection of HDAC2 expression may help us screen patients at increased risk of malignant behavior for PGC.
C1 [Du, Xilin] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Zhao, Huadong] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Zang, Li] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Song, Nuan] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Yang, Tao] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Dong, Rui] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Yin, Jikai] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Wang, Chengguo] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
[Lu, Jianguo] Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
RP Wang, Ch (reprint author), Fourth Military Medical University, Tangdu Hospital, Department of general surgery, 710038 Xi’an, China.
EM chengguo@fmmu.edu.cn
CR Misra S, Chaturvedi A, Misra NC, Sharma ID, 2003, Carcinoma of the gallbladder. Lancet Oncol 4:167–176
Chen Y, Chen Y, Yu G, Ding H, 2011, Lymphangiogenic and angiogentic microvessel density in gallbladder carcinoma. Hepatogastroenterology 58:20–25
Araida T, Higuchi R, Hamano M, Kodera Y, Takeshita N, Ota T, Yoshikawa T, Yamamoto M, Takasaki K, 2009, Should the extrahepatic bile duct be resected or preserved in R0 radical surgery for advanced gallbladder carcinoma? results of a Japanese Society of Biliary Surgery Survey: a multicenter study. Surg Today 39:770– 779
Kokudo N, Makuuchi M, Natori T, Sakamoto Y, Yamamoto J, Seki M, Noie T, Sugawara Y, Imamura H, Asahara S, Ikari T, 2003, Strategies for surgical treatment of gallbladder carcinoma based on information available before resection. Arch Surg 138:741–750
Davies GF, Ross AR, Arnason TG, Juurlink BH, Harkness TA, 2010, Troglitazone inhibits histone deacetylase activity in breast cancer cells. Cancer Lett 288:236–250
Brandl A, Heinzel T, Kramer OH, 2009, Histone deacetylases: salesmen and customers in the post-translational modification market. Biol Cell Auspices Eur Cell Biol Organ 101:193–205
Ishdorj G, Graham BA, Hu X, Chen J, Johnston JB, Fang X, Gibson SB, 2008, Lysophosphatidic acid protects cancer cells from histone deacetylase, HDAC, inhibitor-induced apoptosis through activation of HDAC. J Biol Chem 283:16818–16829
Mehdi O, Francoise S, Sofia CL, Urs G, Kevin Z, Bernard S, Igor S, Anabela CD, Dominique L, Eric M, Ali O, 2012, HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat, LBH589, and trichostatine, TSA). Pancreatology 12:146–155
Spiegel S, Milstien S, Grant S, 2012, Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy. Oncogene 31:537–551
Lee JH, Jeong EG, Choi MC, Kim SH, Park JH, Song SH, Park J, Bang YJ, Kim TY, 2010, Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells. Mol Cells 30:107–112
Xu LN, Wang X, Zou SQ, 2008, Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines. World J Gastroenterol 14:2578–2581
Yamaguchi J, Sasaki M, Sato Y, Itatsu K, Harada K, Zen Y, Ikeda H, Nimura Y, Nagino M, Nakanuma Y, 2010, Histone deacetylase inhibitor, SAHA, and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma. Cancer Sci 101:355–362
Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, Digiovanni J, Kiguchi K., 2012, The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol. In press
Willis-Martinez D, Richards HW, Timchenko NA, Medrano EE, 2010, Role of HDAC1 in senescence, aging, and cancer. Exp Gerontol 45:279–285
Schuler S, Fritsche P, Diersch S, Arlt A, Schmid RM, Saur D, Schneider G, 2010, HDAC2 attenuates TRAIL-induced apoptosis of pancreatic cancer cells. Mol Cancer 9:80
Jung KH, Noh JH, Kim JK, Eun JW, Bae HJ, Xie HJ, Chang YG, Kim MG, Park H, Lee JY, Nam SW, 2012, HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins. J Cell Biochem 113:2167–2177
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Quint K, Agaimy A, Di Fazio P, Montalbano R, Steindorf C, Jung R, Hellerbrand C, Hartmann A, Sitter H, Neureiter D, Ocker M, 2011, Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC. Virchows Arch 459:129–139
Aghdassi A, Sendler M, Guenther A, Mayerle J, Behn CO, Heidecke CD, Friess H, Buchler M, Evert M, Lerch MM, Weiss FU, 2012, Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer. Gut 61:439– 448
Ramsey MR, He L, Forster N, Ory B, Ellisen LW, 2011, Physical association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res 71:4373–4379
de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB, 2003, Histone deacetylases, HDACs): characterization of the classical HDAC family. Biochem J 370:737–749
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Harms KL, Chen X, 2007, Histone deacetylase 2 modulates p53 transcriptional activities through regulation of p53-DNA binding activity. Cancer Res 67:3145–3152
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Chang HH, Chiang CP, Hung HC, Lin CY, Deng YT, Kuo MY, 2009, Histone deacetylase 2 expression predicts poorer prognosis in oral cancer patients. Oral Oncol 45:610–614
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 397
EP 403
DI 10.1007/s12253-012-9592-y
PG 7
ER
PT J
AU Wang, K
Jia, Z
Zou, J
Zhang, A
Wang, G
Hao, J
Wang, Y
Yang, Sh
Pu, P
AF Wang, Kun
Jia, Zhifan
Zou, Jian
Zhang, Anling
Wang, Guangxiu
Hao, Jianwei
Wang, Yirong
Yang, Shuxu
Pu, Peiyu
TI Analysis of hsa-miR-30a-5p Expression in Human Gliomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; miR-30a-5p; Ex
ID Glioma; miR-30a-5p; Ex
AB Our previous study demonstrated that miR-30a-5p was upregulated in six malignant glioma cell lines by micro- RNA(miRNA) array. For further verification of this finding, the expression of miR-30a-5p in 7 more malignant glioma cell lines, 43 freshly resected glioma samples and 75 archival paraffin embedded glioma specimens with different grade of malignancy were examined by qRT-PCR and in situ hybridization (ISH). Here, we present the first evidence that miR-30a-5p is overexpressed in glioma cell lines and glioma samples as compared to the normal brain tissues (NBTs), and its expression level is positively correlated with tumor grade of malignancy. It is concluded that miR-30a-5p may have the potential as a diagnostic or prognostic marker of gliomas and as the target of miRNA-based glioma therapy in further studies.
C1 [Wang, Kun] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Jia, Zhifan] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, Heping District, 300052 Tianjin, China.
[Zou, Jian] School of Medicine, Zhejiang University, Women’s Hospital, Women’s Reproductive Health Laboratory of Zhejiang Province, 310006 Hangzhou, China.
[Zhang, Anling] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, Heping District, 300052 Tianjin, China.
[Wang, Guangxiu] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, Heping District, 300052 Tianjin, China.
[Hao, Jianwei] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, Heping District, 300052 Tianjin, China.
[Wang, Yirong] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Yang, Shuxu] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Pu, Peiyu] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, Heping District, 300052 Tianjin, China.
RP Pu, P (reprint author), Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
EM pupeiyu33@hotmail.com
CR Eyler CE, Foo WC, LaFiura KM et al, 2008, Brain cancer stem cells display preferential sensitivity to Akt inhibition. Stem Cells 26:3027–3036
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 405
EP 411
DI 10.1007/s12253-012-9593-x
PG 7
ER
PT J
AU Abdel-Aziz, A
Mohamed, AM
Akl, MFF
Taha, NMA
AF Abdel-Aziz, Azza
Mohamed, Ali Mie
Akl, Mohamed Farouk Fatma
Taha, Nageeb M Ahmed
TI Survivin Expression in Medulloblastoma: A Possible Marker for Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medulloblastoma; survivin; survival; antiapoptosis
ID Medulloblastoma; survivin; survival; antiapoptosis
AB Medulloblastomas are highly invasive tumors which are generally disseminated at the time of diagnosis. High and continued morbidity and mortality have prompted the search for new biologic markers that might be used for targeted therapy to minimise treatment related side effects. In this work, we studied the positive expression of survivin in medulloblastoma and investigated its relation to clinical, pathologic data and survival. Tumor tissue specimens from 47 patients with medulloblastoma who underwent primary surgical treatment from June 2002 to June 2006 at the Mansoura university hospital, Egypt were collected. Paraffin sections of all samples were submitted for immunohistochemistry using anti-survivin antibody. The relation between the percentage of positive survivin cells with clinical, pathological and survival data was evaluated Results: In 47 cancer tissue specimens, one case large-cell-anaplastic (1.12 %), tweleve cases desmoplastic (25.53 %) and 34 cases classic medulloblastomas (72.34 %). The immunohistochemical expression of survivin was nulear with moderate intensity. It does not correlate with either age or sex. There was a significant negative correlation of survivin expression with survival (p<0.001), where negative survivin immunostaining was associated with prolonged overall and disease free survival, while survivin expression was associated with shortened survival. Conclusion: Survivin expression correlate with the clinical outcome with poor prognosis and could be a potential predictive factor for recurrence or metastasis.
C1 [Abdel-Aziz, Azza] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Mohamed, Ali Mie] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Akl, Mohamed Farouk Fatma] Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine DepartmentMansoura, Egypt.
[Taha, Nageeb M Ahmed] Mansoura University, Faculty of Medicine, Neurosurgery departmentMansoura, Egypt.
RP Akl, MFF (reprint author), Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine Department, Mansoura, Egypt.
EM fatmaakl@yahoo.com
CR Bowers DC, Gargan L, Weprin BE, Muline AF, Elterman RD, Munoz L, Giller CA, Winick NJ, 2007, Impact of site of tumor recurrence upon survival for children with recurrent or progressive medulloblastoma. J Neurosurg 107(1 Suppl Pediatrics): 5–10
Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A, 2008, Medulloblastoma: from molecular pathology to therapy review. Clin Cancer Res 14(4):971–976
Sasaki T, Lopes MBS, Hankins GR, Helm GA, 2002, Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system. Acta Neuropathol 104:105–109
Li XN, Shu Q, Su JM, Adesina AM, Wong KK, Perlaky L, Antalffy BA, Blaney SM, Lau CC, 2007, Differential expression of survivin splice isoforms in medulloblastomas. Neuropathol Appl Neurobiol 33:67–76
Liu R, Mitchell DA, 2010, Survivin as an immunotherapeutic target for adult and pediatric malignant brain tumors. Cancer Immunol Immunother 59:183–193
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Haberler C, Slavc I, Czech T, Gelpi E, Heinzl H, Budka H, Urban C, Scarpatetti M, Ebetsberger-Dachs G, Schindler C, Jones N, Klein-Franke A, Maier H, Jauk B, Kiefer A, Hainfellner JA, 2006, Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome. Eur J Cancer 42(17):2996–3003
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 413
EP 419
DI 10.1007/s12253-012-9594-9
PG 7
ER
PT J
AU Smardova, J
Liskova, K
Ravcukova, B
Kubiczkova, L
Sevcikova, S
Michalek, J
Svitakova, M
Vybihal, V
Kren, L
Smarda, J
AF Smardova, Jana
Liskova, Kvetoslava
Ravcukova, Barbora
Kubiczkova, Lenka
Sevcikova, Sabina
Michalek, Jaroslav
Svitakova, Miluse
Vybihal, Vaclav
Kren, Leos
Smarda, Jan
TI High Frequency of Temperature-Sensitive Mutants of p53 in Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; p53 tumor suppressor; FASAY; Temperature-sensitive mutations; p53 gene deletion
ID Glioblastoma; p53 tumor suppressor; FASAY; Temperature-sensitive mutations; p53 gene deletion
AB Glioblastoma is the most common and the most aggressive type of brain cancer. Aberrations of the RTK/RAS/PI3K-, p53-, and RB cell signaling pathways were recognized as a core requirement for pathogenesis of glioblastoma. The p53 tumor suppressor functions as a transcription factor transactivating expression of its target genes in response to various stress stimuli. We determined the p53 status in 36 samples of glioblastoma by functional analyses FASAY and split assay. Seventeen p53 mutations were detected and further analyzed by cDNA and gDNA sequencing in 17 patients (47.2 %). Fifteen (88.2 %) of the mutations were missense mutations causing amino acid substitutions, seven of them exhibited temperature-sensitivity. Two mutations were determined as short deletions, one of them causing formation of premature termination codon in position 247. Fluorescent in situ hybridization revealed the loss of the p53- specific 17p13.3 locus in four of 33 analyzed samples (12 %). In 12 out of 30 samples (40 %), the p53 protein accumulation was shown by immunoblotting. There was high (80 %) concordance between the presence of the clonal p53 mutation and the p53 protein accumulation.
C1 [Smardova, Jana] University Hospital Brno, Department of Pathology, Jihlavska 20, 625 00 Brno, Czech Republic.
[Liskova, Kvetoslava] University Hospital Brno, Department of Pathology, Jihlavska 20, 625 00 Brno, Czech Republic.
[Ravcukova, Barbora] Centre for Cardiovascular Surgery and Transplantation, Molecular Genetics LaboratoryBrno, Czech Republic.
[Kubiczkova, Lenka] Masaryk University, Faculty of Medicine, Department of Pathological PhysiologyBrno, Czech Republic.
[Sevcikova, Sabina] Masaryk University, Faculty of Medicine, Department of Pathological PhysiologyBrno, Czech Republic.
[Michalek, Jaroslav] Masaryk University, Faculty of Medicine, Department of PharmacologyBrno, Czech Republic.
[Svitakova, Miluse] University Hospital Brno, Department of Pathology, Jihlavska 20, 625 00 Brno, Czech Republic.
[Vybihal, Vaclav] Faculty Hospital Brno, Department of NeurosurgeryBrno, Czech Republic.
[Kren, Leos] University Hospital Brno, Department of Pathology, Jihlavska 20, 625 00 Brno, Czech Republic.
[Smarda, Jan] Masaryk University, Faculty of Science, Department of Experimental BiologyBrno, Czech Republic.
RP Smardova, J (reprint author), University Hospital Brno, Department of Pathology, 625 00 Brno, Czech Republic.
EM janasmarda@seznam.cz
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 421
EP 428
DI 10.1007/s12253-012-9596-7
PG 8
ER
PT J
AU Wang, Q
Wang, N
Shao, G
Qian, J
Shen, D
Fei, Y
Mao, W
Wu, D
AF Wang, Qiong
Wang, Nanyao
Shao, Guoyi
Qian, Jianzhong
Shen, Dong
Fei, Yanhua
Mao, Weidong
Wu, Dan
TI Relationship Between Gastric Cancer Tau Protein Expression and Paclitaxel Sensitivity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Tau protein; Paclitaxel; Sensitivity
ID Gastric cancer; Tau protein; Paclitaxel; Sensitivity
AB The abnormal expression of Tau protein in breast cancer tissue affects paclitaxel sensitivity. The abnormal expression also exists in gastric carcinoma. Therefore, we speculate that the expression levels of Tau protein is closely related to paclitaxel sensitivity in gastric cancer, thus affecting the efficacy of paclitaxel. In this study, we used immunohistochemical methods to detect Tau protein expression levels in 47 cases of gastric cancer specimens. We also used Western blot to detect the level of Tau protein expression in gastric cancer cell lines and to check the efficacy of paclitaxel in vitro application. Findings indicate that Tau protein expression rate can reach as high as (+ +–+ + +) 63.83 % in gastric cancer. Paclitaxel induces inhibition and apoptosis with low expression of Tau protein in gastric cancer cell lines (P<0.05). The level of Tau protein expression is significantly correlated with paclitaxel efficacy. If confirmed by further studies, the Tau protein can be another useful marker of gastric cancer, thereby leading to the application of paclitaxel in cancer treatment.
C1 [Wang, Qiong] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
[Wang, Nanyao] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
[Shao, Guoyi] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Surgery, 214400 Wuxi, China.
[Qian, Jianzhong] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Pathology, 214400 Wuxi, China.
[Shen, Dong] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
[Fei, Yanhua] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
[Mao, Weidong] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
[Wu, Dan] The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
RP Wang, Q (reprint author), The Affiliated Jiangyin Hospital of Southeast University Medical College, Department of Oncology, 214400 Wuxi, China.
EM qiongwangcn@163.com
CR Zheng LZ, Chen Q, 2005, Gastric cancer chemotherapy status. Gastroenterology 10:178–181
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Qiu LX, Qian XP, Liu B, 2009, Research progress on Taxane drug efficacy forecast molecular. Modern Oncol 17:1583–1584
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 429
EP 435
DI 10.1007/s12253-012-9598-5
PG 7
ER
PT J
AU Snyder, DA
Dulin-Smith, NA
Houston, HR
Durban, NA
Brisbin, JB
Oostra, DTy
Marshall, TJ
Kahwash, MB
Pierson, RCh
AF Snyder, D Andrew
Dulin-Smith, N Ashley
Houston, H Ronald
Durban, N Ashley
Brisbin, J Bethany
Oostra, D Tyler
Marshall, T Jordan
Kahwash, M Basil
Pierson, R Christopher
TI Expression Pattern of Id Proteins in Medulloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medulloblastoma; Id proteins; Id2; Id3; Cerebellum
ID Medulloblastoma; Id proteins; Id2; Id3; Cerebellum
AB Inhibitor of DNA binding or inhibitor of differentiation (Id) proteins are up regulated in a variety of neoplasms, particularly in association with high-grade, poorly differentiated tumors, while differentiated tissues show little or no Id expression. The four Id genes are members of the helix-loop-helix (HLH) family of transcription factors and act as negative regulators of transcription by binding to and sequestering HLH complexes. We tested the hypothesis that Id proteins are overexpressed in medulloblastoma by performing immunohistochemistry using a medulloblastoma tissue microarray with 45 unique medulloblastoma and 11 normal control cerebella, and antibodies specific for Id1, Id2, Id3, and Id4. A semi-quantitative staining score that took staining intensity and the proportion of immunoreactive cells into account was used. Id1 was not detected in normal cerebella or in medulloblastoma cells, but 78 % of tumors showed strong Id1 expression in endothelial nuclei of tumor vessels. Id2 expression was scant in normal cerebella and increased in medulloblastoma (median staining score: 4). Id3 expression was noted in some neurons of the developing cerebellar cortex, but it was markedly up regulated in medulloblastoma (median staining score: 12) and in tumor endothelial cells. Id4 was not expressed in normal cerebella or in tumor cells. Id2 or Id3 overexpression drove proliferation in medulloblastoma cell lines by altering the expression of critical cell cycle regulatory proteins in favor of cell proliferation. This study shows that Id1 expression in endothelial cells may contribute to angiogenic processes and that increased expression of Id2 and Id3 in medulloblastoma is potentially involved in tumor cell proliferation and survival.
C1 [Snyder, D Andrew] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Dulin-Smith, N Ashley] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Houston, H Ronald] Nationwide Children’s Hospital, Department of Pathology and Laboratory MedicineColumbus, OH, USA.
[Durban, N Ashley] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Brisbin, J Bethany] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Oostra, D Tyler] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Marshall, T Jordan] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Kahwash, M Basil] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
[Pierson, R Christopher] Nationwide Children’s Hospital, The Research InstituteColumbus, OH, USA.
RP Pierson, RCh (reprint author), Nationwide Children’s Hospital, The Research Institute, Columbus, USA.
EM christopher.pierson@nationwidechildrens.org
CR Louis DN OH, Wiestler OD, Cavenee WK, eds,, 2007, WHO classification of tumors of the central nervous system. Lyon
Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM, 2001, Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children’s Cancer Group study. J Clin Oncol 19(15):3470–3476
Perk J, Iavarone A, Benezra R, 2005, Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer 5(8):603–614
Jen Y, Manova K, Benezra R, 1997, Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis. Dev Dyn 208(1):92–106
Lyden D, Young AZ, Zagzag D, YanW, GeraldW, O’Reilly R et al, 1999, Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401(6754):670–677
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Fong S, Debs RJ, Desprez PY, 2004, Id genes and proteins as promising targets in cancer therapy. Trends Mol Med 10(8):387– 392
Ruzinova MB, Benezra R, 2003, Id proteins in development, cell cycle and cancer. Trends Cell Biol 13(8):410–418
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Prabhu S, Ignatova A, Park ST, Sun XH, 1997, Regulation of the expression of cyclin-dependent kinase inhibitor p21 by E2A and Id proteins. Mol Cell Biol 17(10):5888–5896
Ayrault O, Zindy F, Rehg J, Sherr CJ, Roussel MF, 2009, Two tumor suppressors, p27Kip1 and patched-1, collaborate to prevent medulloblastoma. Mol Cancer Res 7(1):33–40
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Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC et al, 2012, Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123(4):465–472
Oliver TG, Grasfeder LL, Carroll AL, Kaiser C, Gillingham CL, Lin SM et al, 2003, Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc Natl Acad Sci U S A 100(12):7331–7336
Lasorella A, Stegmuller J, Guardavaccaro D, Liu G, Carro MS, Rothschild G et al, 2006, Degradation of Id2 by the anaphasepromoting complex couples cell cycle exit and axonal growth. Nature 442(7101):471–474
Iavarone A, Garg P, Lasorella A, Hsu J, Israel MA, 1994, The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein. Genes Dev 8(11):1270–1284
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Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Yet al, 2001, Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Nature 409(6823):1067–1070
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 437
EP 446
DI 10.1007/s12253-012-9599-4
PG 10
ER
PT J
AU Mu, F
Liu, ShP
Zhou, XL
Chen, JB
Li, HB
Zuo, JSh
Xu, KCh
AF Mu, Feng
Liu, Shu-Peng
Zhou, Xu-Long
Chen, Ji-Bing
Li, Hai-Bo
Zuo, Jian-Sheng
Xu, Ke-Cheng
TI Prevention of Needle-Tract Seeding by Two-Step Freezing after Lung Cancer Biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biopsy; Percutaneous cryoablation; Lung cancer; Pathology
ID Biopsy; Percutaneous cryoablation; Lung cancer; Pathology
AB Fine-needle aspiration biopsy is a method to detect malignancy for undetermined pulmonary nodules, but has the potential to spread malignant cells from the tumor to the pleural cavity or chest wall. We developed a two-step freezing method to avoid needle-tract seeding, by use of percutaneous cryoablation after biopsy but before the biopsy needle was removed. A man aged 72 years was admitted because of a large mass in right upper lobe. After biopsy, the patient underwent surgery. Pathological assessment of the resected tumor showed that tissue around the biopsy probe and cryoprobe had been killed before needle withdrawal.
C1 [Mu, Feng] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Liu, Shu-Peng] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Zhou, Xu-Long] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Chen, Ji-Bing] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Li, Hai-Bo] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Zuo, Jian-Sheng] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
[Xu, Ke-Cheng] Chinese Academy of Science, Institutes of Biomedicine and Health, No. 91 Judezhong Road, Haizhu District, 510305 Guangzhou, Guangdong, China.
RP Chen, JB (reprint author), Chinese Academy of Science, Institutes of Biomedicine and Health, 510305 Guangzhou, China.
EM jibingchen@yahoo.com.cn
CR Moloo Z, Finley RJ, Lefcoe MS, Turner-Smith L, Craig ID, 1985, Possible spread of bronchogenic carcinoma to the chest wall after a transthoracic fine needle aspiration biopsy. A case report. Acta Cytol 29:167–169
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Sawabata N, Ohta M, Maeda H, 2000, Fine-needle aspiration cytologic technique for lung cancer has a high potential of malignant cell spread through the tract. Chest 118:936–939
Vignoli M, Rossi F, Chierici C, Terragni R, De Lorenzi D, Stanga M et al, 2007, Needle tract implantation after fine needle aspiration biopsy, FNAB, of transitional cell carcinoma of the urinary bladder and adenocarcinoma of the lung. Schweiz Arch Tierheilkd 149:314–318
Inoue M, Nakatsuka S, Yashiro H, Ito N, Izumi Y, Yamauchi Y et al, 2012, Percutaneous cryoablation of lung tumors: feasibility and safety. J Vasc Interv Radiol 23:295–302, quiz 305
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Hashimoto K, Izumi Y, Yamauchi Y, Yashiro H, Inoue M, Nakatsuka S et al, 2012, Prediction of the critical thermal zone during pulmonary cryoablation on computed tomography from correlated experimental and clinical findings. J Thorac Cardiovasc Surg., DOI 10.1016/j.jtcvs.2012.03.029
Hinshaw JL, Littrup PJ, Durick N, Leung W, Lee FT Jr, Sampson L et al, 2010, Optimizing the protocol for pulmonary cryoablation: a comparison of a dual- and triple-freeze protocol. Cardiovasc Intervent Radiol 33:1180–1185
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Nakatsuka S, Yashiro H, Inoue M, Kuribayashi S, Kawamura M, Izumi Y et al, 2010, On freeze-thaw sequence of vital organ of assuming the cryoablation for malignant lung tumors by using cryoprobe as heat source. Cryobiology 61:317–326
Berner A, Lund-Iversen M, Nesland JM, 2011, Fine needle aspirations in oncology. Arkh Patol 73:21–26
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Littrup PJ, Jallad B, Vorugu V, Littrup G, Currier B, GeorgeMet al, 2009, Lethal isotherms of cryoablation in a phantom study: effects of heat load, probe size, and number. J Vasc Interv Radiol 20:1343–1351
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 447
EP 450
DI 10.1007/s12253-012-9601-1
PG 4
ER
PT J
AU Sassi, A
Popielarski, M
Synowiec, E
Morawiec, Z
Wozniak, K
AF Sassi, Agnieszka
Popielarski, Marcin
Synowiec, Ewelina
Morawiec, Zbigniew
Wozniak, Katarzyna
TI BLM and RAD51 Genes Polymorphism and Susceptibility to Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Genepolymorphism; BLM gene; RAD51 gene; DNA double-strand breaks
ID Breast cancer; Genepolymorphism; BLM gene; RAD51 gene; DNA double-strand breaks
AB DNA repair by homologous recombination is one of the main processes of DNA double strand breaks repair. In the present work we performed a case-control study (304 cases and 319 controls) to check an association between the genotypes of the c.-61 G>T and the g.38922 C>G polymorphisms of the RAD51 gene and the g.96267 A>C and the g.85394 A>G polymorphisms of the BLM gene and breast cancer occurrence. Genotypes were determined in DNA from peripheral blood by PCR-RLFP and by PCRCTPP. We observed an association between breast cancer occurrence and the T/G genotype (OR 4.41) of the c.-61 G>T-RAD51 polymorphism, the A/A genotype (OR 1.69) of the g.85394 A>G-BLM polymorphism and the A/A genotype (OR 2.49) of the g.96267 A>C-BLM polymorphism. Moreover, we demonstrated a correlation between intra- and intergenes genotypes combinations and breast cancer occurrence. We found a correlation between progesterone receptor expression and the T/G genotype (OR 0.57) of the c.-61 G>T- RAD51 polymorphism. We also found a correlation between the T/G genotype (OR 1.86) and the T/T genotype (OR 0.56) of the c.-61 G>T- RAD51 polymorphism and the lymph node metastasis. We showed an association between the A/A genotype (OR 2.45) and the A/C genotype (OR 0.41) of the g.96267 A>C-BLM polymorphism and G3 grade of tumor. Our results suggest that the variability of the RAD51 and BLM genes may play a role in breast cancer occurrence. This role may be underlined by a common interaction between these genes.
C1 [Sassi, Agnieszka] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Popielarski, Marcin] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Synowiec, Ewelina] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Morawiec, Zbigniew] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Wozniak, Katarzyna] University of Lodz, Department of Molecular GeneticsLodz, Poland.
RP Wozniak, K (reprint author), University of Lodz, Department of Molecular Genetics, Lodz, Poland.
EM wozniak@biol.uni.lodz.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 451
EP 459
DI 10.1007/s12253-013-9602-8
PG 9
ER
PT J
AU Wang, LP
Chen, ShW
Zhuang, ShM
Li, H
Song, M
AF Wang, Li-Ping
Chen, Shu-Wei
Zhuang, Shi-Min
Li, Huan
Song, Ming
TI Galectin-3 Accelerates the Progression of Oral Tongue Squamous Cell Carcinoma via a Wnt/β-catenin-Dependent Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Galectin-3; Oral tongue squamous cell carcinoma; Wnt/β-catenin; Clinicopathological significance; Mechanism
ID Galectin-3; Oral tongue squamous cell carcinoma; Wnt/β-catenin; Clinicopathological significance; Mechanism
AB The purpose of this study was to elucidate the clinicopathological significance and mechanism of action of galectin-3 in oral tongue squamous cell carcinoma (OTSCC). Here, the expression of galectin-3 was quantified in OTSCC (n=68) and paired OTSCC and normal surrounding tissues (n=10) using immunohistochemical staining. Tca8113 OTSCC cells were transfected with a plasmid expressing galectin-3 cDNA or siRNA against galectin-3. Cell proliferation, migration and invasion were measured using the MTT assay, Matrigel-coated Transwell migration assay and wound healing assay. The effect of galectin-3 on the Wnt/β-catenin signaling pathway and epithelial mesenchymal transition (EMT) were investigated using a plasmid expressing the Wnt antagonist dickkopf 1 (DKK1) and Western blotting. Galectin-3 was expressed at significantly higher levels in OTSCC than the normal adjacent tissues; galectin-3 expression correlated strongly with pathological stage, pathological grade and lymph node invasion in OTSCC. Overexpression of galectin-3 promoted Tca8113 cell proliferation, migration and invasion, upregulated Wnt protein expression, activated β-catenin and induced the EMT; knockdown of galectin-3 had the opposite effects. Co-transfection of Tca8113 cells overexpressing galectin-3 with the Wnt antagonist DKK1 reduced the ability of galectin-3 to increase cell proliferation, migration and invasion, reduced upregulation of Wnt, inhibited β-catenin activation and abrogated the EMT, demonstrating that the Wnt/β-catenin signaling pathway mediated the effects of galectin-3. Galectin-3 plays an important role in the progression of OTSCC via activation of the Wnt/β-catenin signaling pathway.
C1 [Wang, Li-Ping] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Chen, Shu-Wei] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Zhuang, Shi-Min] The Third Affiliated Hospital of Sun Yat-sen University, Department of Otolaryngology-Head & Neck SurgeryGuangzhou, China.
[Li, Huan] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
[Song, Ming] Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 651 Dongfeng Dong Road, 510060 Guangzhou, China.
RP Song, M (reprint author), Sun Yat-sen University Cancer Center, Department of Head and Neck Surgery, 510060 Guangzhou, China.
EM songming@sysucc.org.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 461
EP 474
DI 10.1007/s12253-013-9603-7
PG 14
ER
PT J
AU Zhang, K
Bai, P
Shi, Sh
Zhou, B
Wang, Y
Song, Y
Rao, L
Zhang, L
AF Zhang, Kui
Bai, Peng
Shi, Shaoqing
Zhou, Bin
Wang, Yanyun
Song, Yaping
Rao, Li
Zhang, Lin
TI Association of Genetic Variations in RTN4 3’-UTR with Risk of Uterine Leiomyomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RTN4; Uterine Leiomyoma (UL); Polymorphism; Genetic susceptibility
ID RTN4; Uterine Leiomyoma (UL); Polymorphism; Genetic susceptibility
AB This pilot case-control study was conducted to test the hypothesis that the TATC (rs71682890) and CAA (rs34917480) insertion/deletion polymorphisms of RTN4 3’- UTR are associated with the susceptibility to uterine leiomyoma (UL). The study recruited 286 premenopausal women with UL and 450 unrelated postmenopausal women not presenting the disease as control subjects. The polymorphisms of rs71682890 and rs34917480 were genotyped with the method of polymerase chain reaction polyacrylamide gel electrophoresis (PCR - PAGE). No statistically significant association was observed between the TATC insertion/deletion polymorphism and UL risk. However, increased UL risk was identified to be significantly associated with CAA insertion/deletion polymorphism in the recessive and codominant model. The present study provided evidence for the first time that CAA polymorphism in RTN4 3’-UTR, but not TATC polymorphism may be involved in susceptibility to UL.
C1 [Zhang, Kui] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Forensic Biology, 610041 Chengdu, Sichuan, China.
[Bai, Peng] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Forensic Biology, 610041 Chengdu, Sichuan, China.
[Shi, Shaoqing] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Immunology, 610041 Chengdu, Sichuan, China.
[Zhou, Bin] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, 610041 Chengdu, Sichuan, China.
[Wang, Yanyun] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, 610041 Chengdu, Sichuan, China.
[Song, Yaping] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, 610041 Chengdu, Sichuan, China.
[Rao, Li] West China Hospital of Sichuan University, Department of Cardiology, 610041 Chengdu, Sichuan, China.
[Zhang, Lin] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Forensic Biology, 610041 Chengdu, Sichuan, China.
RP Zhang, L (reprint author), Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Forensic Biology, 610041 Chengdu, China.
EM zhanglin@scu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 475
EP 479
DI 10.1007/s12253-013-9604-6
PG 5
ER
PT J
AU Le Donne, M
Giuffre, G
Caruso, C
Nicotina, AP
Alibrandi, A
Scalisi, R
Simone, A
Chiofalo, B
Triolo, O
AF Le Donne, Maria
Giuffre, Giuseppe
Caruso, Carmela
Nicotina, Antonio Piero
Alibrandi, Angela
Scalisi, Rosalba
Simone, Angela
Chiofalo, Benito
Triolo, Onofrio
TI Human Papillomavirus Types Distribution in Eastern Sicilian Females with cervical lesions. A Correlation with Colposcopic and Histological Findings
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; Genotypes; Distribution; Colposcopy; Cervical lesion
ID Human papillomavirus; Genotypes; Distribution; Colposcopy; Cervical lesion
AB To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17–68 years, with previous cytological abnormalities, were included in this study. HPVDNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6%) followed by HPV-31 (26.9%), −6 (18.6 %), −58 (8.8 %), −18 (6.7 %), −66 (5.7 %), −52 and −53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P=0.023; and HPV-53 P=0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7%, 31.2%, 44%and 37.2%of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.
C1 [Le Donne, Maria] Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Via Consolare Valeria, 98125 Messina, Italy.
[Giuffre, Giuseppe] Azienda Ospedaliera Universitaria, Department of Human Pathology, Via Consolare Valeria, 98125 Messina, Italy.
[Caruso, Carmela] Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Via Consolare Valeria, 98125 Messina, Italy.
[Nicotina, Antonio Piero] Azienda Ospedaliera Universitaria, Department of Human Pathology, Via Consolare Valeria, 98125 Messina, Italy.
[Alibrandi, Angela] University of Messina, Department of Economical, Business and Environmental Sciences and Quantitative Methods, Via dei Verdi n.75, 98124 Messina, Italy.
[Scalisi, Rosalba] Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Via Consolare Valeria, 98125 Messina, Italy.
[Simone, Angela] Azienda Ospedaliera Universitaria, Department of Human Pathology, Via Consolare Valeria, 98125 Messina, Italy.
[Chiofalo, Benito] Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Via Consolare Valeria, 98125 Messina, Italy.
[Triolo, Onofrio] Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Via Consolare Valeria, 98125 Messina, Italy.
RP Le Donne, M (reprint author), Azienda Ospedaliera Universitaria, ‘Policlinico G. Martino’, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, 98125 Messina, Italy.
EM marialedonne@tin.it
CR Giorgi Rossi P, Bisanzi S, Paganini I et al, 2010, Prevalence of HPV high and low risk types in cervical samples from the Italian general population: a population based study. BMC Infect Dis 20(10):214
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De Francesco MA, Gargiulo F, Schreiber C, Ciravolo G, Salinaio F, Manca N, 2005, Detection and genotyping of human papillomavirus in cervical samples from Italian patients. J Med Virol 75:588–592
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Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE, 2011, Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 103:368–383
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 481
EP 487
DI 10.1007/s12253-013-9605-5
PG 7
ER
PT J
AU Liu, Ch
Cui, Q
Shu, C
Guo, J
Li, D
AF Liu, Cheng
Cui, Qiu
Shu, Cuili
Guo, Jun
Li, Dingfeng
TI Comprehensive Treatment Based on Intra-arterial Chemotherapy for Distal Femur Neoplasms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intra-arterial chemotherapy; SIDS; Distal femur; Bone neoplasms
ID Intra-arterial chemotherapy; SIDS; Distal femur; Bone neoplasms
AB To investigate the clinical efficacy of intra-arterial chemotherapy by subcutaneous implantable delivery system (SIDS) in the treatment of distal femur neoplasm. From March 2002 to December 2009, 51 patients were treated with SIDS intra-femoral artery chemotherapy, followed by customized prosthetic reconstruction, including 45 patients of osteosarcoma and 6 malignant fibrous histiocytoma in distal femur. The average follow-up period was 64 months (ranging between 24 and 116 months) to track on the efficacy of chemotherapy, which shows that 96.1 % of patients got pain relief, 70.6 % of patients had significant radiological change, and 82.4 % of paitents with medium to severe pathological variation responded to the chemotherapy. Local recurrence happened in 4 cases, 3 cases are alive with disease, 4 cases died because of pulmonary metastases and other 40 patients are free of local recurrence or distant metastasis. SIDS intra-femur artery chemotherapy can improve clinical outcome of DFN, and provide effective method for treatment of DFN when combined with customized prosthetic reconstruction.
C1 [Liu, Cheng] 307 Hospital of PLA, Department of Orthopedics, NO 8 East Street, Fengtai District, 100071 Beijing, China.
[Cui, Qiu] 307 Hospital of PLA, Department of Orthopedics, NO 8 East Street, Fengtai District, 100071 Beijing, China.
[Shu, Cuili] 307 Hospital of PLA, Department of Orthopedics, NO 8 East Street, Fengtai District, 100071 Beijing, China.
[Guo, Jun] 307 Hospital of PLA, Department of Orthopedics, NO 8 East Street, Fengtai District, 100071 Beijing, China.
[Li, Dingfeng] 307 Hospital of PLA, Department of Orthopedics, NO 8 East Street, Fengtai District, 100071 Beijing, China.
RP Li, D (reprint author), 307 Hospital of PLA, Department of Orthopedics, 100071 Beijing, China.
EM 307yygk@sina.com
CR Wilkins RM, Cullen JW, Camozzi AB et al, 2005, Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity. Clin Orthop Relat Res 438:128–136
Zhang HJ, Yang JJ, Lu JP et al, 2009, Use of intra-arterial chemotherapy and embolization before limb salvage surgery for osteosarcoma of the lower extremity. Cardiovasc Intervent Radiol 32, 4):672–678
Abe S, Tateishi A, Ogawa K et al, 2001, Long-term local intensive preoperative chemotherapy and joint-preserving conservative surgery for osteosarcoma around the knee. Orthopedics 24(7):671–676
Wilkins RM, Cullen JW, Odom L et al, 2003, Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity. Ann Surg Oncol 10(5):498–507
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Cui Q, Li DF, Liu C et al, 2011, Two case-reports of the limb salvage treatment of osteosarcoma consolidated with obvious pathological fractures. Pathol Oncol Res 17:973–979
Wu CC, Pritsch T, Shehadeh A et al, 2008, The anterior popliteal approach for popliteal exploration, distal femoral resection, and endoprosthetic reconstruction. J Arthroplasty 23(2):254–262
Hugate RR, Wilkins RM, Kelly CM et al, 2008, Intraarterial chemotherapy for extremity osteosarcoma and MFH in adults. Clin Orthop Relat Res 466(6):1292–1301
Gelderblom H, Jinks RC, Sydes M et al, 2011, Survival after recurrent osteosarcoma: data from 3 European Osteosarcoma Intergroup, EOI, randomized controlled trials. Eur J Cancer 47(6):895–902
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 489
EP 493
DI 10.1007/s12253-013-9606-4
PG 5
ER
PT J
AU Giordano, G
Pizzi, S
Azzoni, C
Bottarelli, L
D’Adda, T
AF Giordano, Giovanna
Pizzi, Silvia
Azzoni, Cinzia
Bottarelli, Lorena
D’Adda, Tiziana
TI Primary Squamous Cell Carcinoma of the Endometrium Unrelated to Human Papilloma Virus: A Molecular Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial squamous carcinoma; Allelic imbalance; Aberrant methylation of promoters
ID Endometrial squamous carcinoma; Allelic imbalance; Aberrant methylation of promoters
AB In this paper we report a molecular study of a case of Primary Endometrial Squamous Carcinoma (PESC), in which a Human Papilloma Virus (HPV) infection had been previously excluded by Polymerase Chain Reaction (PCR). The studies performed in an effort to explain the carcinogenesis included immunohistochemical over-expression of p53 and p16 proteins as previously observed in our own papers, plus microsatellite analysis of D10S1765 at 10q23.3 (PTEN) and TP53 at 17p13.1 (P53) as well as the methylation status of the of BRCA1 and p16 promoters using specific PCRs. In this rare malignancy, we found allelic imbalance (AI) at 17p13.1 (P53). Instead, AI at D10S1765 (PTEN) gene was absent. The genetic alteration of p53, with hyper-expression of p53 protein and an absence of abnormalities in the PTEN gene are consistent with the similarities between Uterine Serous Carcinoma (USC) and our case of PESC. The aberrant methylation of both p16 and BCAR1 promoters was not detected in our case. This finding too could imply that ESC is more similar to Uterine Serous Carcinoma than Uterine Endometrioid Carcinoma (UEC). Moreover, the lack of aberrant methylation of p16, which is in accordance with over-expression of p16 immunoreactivity, in the absence of HPV infection may be related to other unknown genetic alterations. In our opinion, it is hard to reach any definite conclusion concerning the carcinogenesis of PESC, because of its rarity and the very few molecular studies reported in the literature. Further studies with more numerous cases and larger molecular analyses are mandatory for this malignancy, to confirm whether it is more closely related to papillary endometrial cancer than to endometrioid carcinoma.
C1 [Giordano, Giovanna] University of Parma, Institute of Pathology, via Antonio Gramsci, 14 43126 Parma, Italy.
[Pizzi, Silvia] University of Parma, Institute of Pathology, via Antonio Gramsci, 14 43126 Parma, Italy.
[Azzoni, Cinzia] University of Parma, Institute of Pathology, via Antonio Gramsci, 14 43126 Parma, Italy.
[Bottarelli, Lorena] University of Parma, Institute of Pathology, via Antonio Gramsci, 14 43126 Parma, Italy.
[D’Adda, Tiziana] University of Parma, Institute of Pathology, via Antonio Gramsci, 14 43126 Parma, Italy.
RP Giordano, G (reprint author), University of Parma, Institute of Pathology, 14 43126 Parma, Italy.
EM giovanna.giordano@unipr.it
CR Klaes R, Friedrich T, Spitkovsky D et al, 2001, Overexpression of p16ink4a as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92:276–284
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 495
EP 499
DI 10.1007/s12253-013-9607-3
PG 5
ER
PT J
AU Dede, K
Mersich, T
Besznyak, I
Zarand, A
Salamon, F
Baranyai, Zs
Landherr, L
Jakab, F
Bursics, A
AF Dede, Kristof
Mersich, Tamas
Besznyak, Istvan
Zarand, Attila
Salamon, Ferenc
Baranyai, Zsolt
Landherr, Laszlo
Jakab, Ferenc
Bursics, Attila
TI Bevacizumab Treatment Before Resection of Colorectal Liver Metastases: Safety, Recovery of Liver Function, Pathologic Assesment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal liver metastases; Preoperative chemotherapy; Bevacizumab; Complications; Functional liver recovery
ID Colorectal liver metastases; Preoperative chemotherapy; Bevacizumab; Complications; Functional liver recovery
AB Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients —(1) CTX+BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection—were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX+BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P=0.72). Only the type of resection was associated with a significantly higher complication rate (p=0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV+CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection.
C1 [Dede, Kristof] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Mersich, Tamas] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Besznyak, Istvan] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Zarand, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Salamon, Ferenc] Fovarosi Uzsoki utcai Korhaz, PathologiaBudapest, Hungary.
[Baranyai, Zsolt] Szent Imre Hospital, Department of SurgeryBudapest, Hungary.
[Landherr, Laszlo] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Jakab, Ferenc] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Bursics, Attila] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
RP Dede, K (reprint author), Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, 1145 Budapest, Hungary.
EM dede.kristof@gmail.com
CR Adam R, Delvart V, Pascal G et al, 2004, Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657
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Scoggins CR, Campbell ML, Landry CS et al, 2009, Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol 16, 1):35–41
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Ribero D, Wang H, Donadon M et al, 2007, Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110(12):2761–2767
Klinger M, Eipeldauer S, Hacker S et al, 2009, Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol 35(5):515– 520
D’Angelica M, Kornprat P, Gonen M et al, 2007, Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched casecontrol study. An Surg Oncol 14:759–765
Ellis LM, Curley SA et al, 2005, Surgical resection after downsizing of colorectal liver metastasis in the era of Bevacizumab. J Clin Oncol 23(22):4853–4855
Reddy SK, Morse MA, Hurwitz HI et al, 2008, Addition of bevacizumab to irinotecan and oxaliplatin based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg 206:96–106
Mahfud M, Breitenstein S, El-Badry AM et al, 2010, Impact of preoperative bevacizumab on complications after resection of colorectal liver metastases: case-matched control study. World J Surg 34(1):92–100
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Dindo D, Demartines N, Clavien PA, 2004, Classification of surgical complications a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213
Dan G, Blazer III, Kishi Y et al, 2008, Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 25(33):5344–5351
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Chua TC, Saxena A, Liauw A et al, 2010, Systematic review of randomized and nonrandomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol 17(2):492–501
Nordlinger B, Van Cutsem E, Gruenberger T, European Colorectal Metastases Treatment Group; Sixth International Colorectal Liver Metastases Workshop et al, 2009, Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol 20(6):985–992
Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA, 2012, Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg 255:237–247
Scappaticci FA, Fehrenbacher L, Cartwright T et al, 2005, Surgical woundhealing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180
Tamandl D, Gruenberger B, Klinger M et al, 2010, Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study. Ann Surg 252(1):124– 130
Kishi Y, Zorzi D, Contreras CM et al, 2010, Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol 17(11):2870–2876
Gordon MS, Margolin K, Talpaz M et al, 2001, Phase I safety and pharmacokineticstudy of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19(3):843–850
Chun YS, Vauthey JN, Boonsirikamchai P et al, 2009, Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal livermetastases. JAMA 302(21):2338–2344
Rubbia-Brandt L, Giostra E, Brezault C et al, 2007, Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol 18:299–304
Dipen MM, Kopetz S, Boonsirikamchai P et al, 2010, Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol 34:1287–1294
Li Chang HH, Leeper WR, Chan G, Quan D, Driman DK, 2012, Infarct-like necrosis. A distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol 36:570–576
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 501
EP 508
DI 10.1007/s12253-013-9608-2
PG 8
ER
PT J
AU de Abreu Pereira, D
Areias, RV
Franco, FM
Benitez, CMM
do Nascimento, MC
de Azevedo, MC
Alves, G
AF de Abreu Pereira, Denise
Areias, Rabello Vivian
Franco, Felipe Marco
Benitez, Carlos Moreira Manuel
do Nascimento, Moreira Cristina
de Azevedo, Maria Carolina
Alves, Gilda
TI Measurement of HER2 in Saliva of Women in Risk of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating HER2; Saliva; NAF; Breast cancer; Impalpable lesion
ID Circulating HER2; Saliva; NAF; Breast cancer; Impalpable lesion
AB HER2 amplification can be present in ductal carcinoma in situ (DCIS). The aim of the present study was to test the feasibility of measuring soluble HER2 in the saliva of patients at risk of breast cancer towards early diagnosis and prognosis.Women with lesions classified as 4 according to BIRADS and women with spontaneous nipple discharge (NAF) were recruited for this study. Quantification of soluble HER2 in saliva was performed using the enzyme immunoassay ELISA. Median values of HER2 were quantified in saliva of the control groups and in the patient groups. The statistical test nonparametric Mann–Whitney was applied for the evaluation of median differences. Although the medians increased with the severity of the clinical status, no significant difference was found in all possibilities (p> 0.05) when comparing the medians among the patients groups. Interestingly, inter-individual HER2 quantity variations in the saliva were detected in this study in some subjects from each group. Considering possible interindividual variations, research on saliva-based circulating HER2 has to be reinforced to ensure its correct application in diagnosis, treatment and in follow-up of breast cancer patients. Older and current issues surrounding the controversy about the appropriate methods for HER2 evaluation are discussed.
C1 [de Abreu Pereira, Denise] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
[Areias, Rabello Vivian] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
[Franco, Felipe Marco] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
[Benitez, Carlos Moreira Manuel] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
[do Nascimento, Moreira Cristina] Instituto Nacional de Cancer, Divisao de Patologia, Av. Cordeiro da Graca, 156, Santo CristoRio de Janeiro, Brazil.
[de Azevedo, Maria Carolina] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
[Alves, Gilda] Instituto Nacional de Cancer, Servico de Hematologia, Pc da Cruz Vermelha, 23, 6º andarRio de Janeiro, Brazil.
RP Alves, G (reprint author), Instituto Nacional de Cancer, Servico de Hematologia, Rio de Janeiro, Brazil.
EM gbrown@inca.gov.br
CR Lang JE, Kuerer HM, 2007, Breast ductal secretions: clinical features, potential uses, and possible applications. Cancer Control 14(4):350–359
Wong DT, 2006, Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc 137(3):313–321
Streckfus C, Bigler L, Dellinger T, Pfeifer M, Rose A, Thigpen JT, 1999, CA 15–3 and c-erbB-2 presence in the saliva of women. Clin Oral Investig 3(3):138–143
Streckfus C, Bigler L, Dellinger T, Dai X, Kingman A, Thigpen JT, 2000, The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. Clin Cancer Res 6(6):2363–2370
Streckfus C, Bigler L, Dellinger T, Dai X, Cox WJ, McArthur A, Kingman A, Thigpen JT, 2001, Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91(2):174–179
Streckfus C, Bigler L, 2005, The use of soluble, salivary c-erbB-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study. Adv Dent Res 18(1):17–24
Esteva FJ, Cheli CD, Fritsche H, Fornier M, Slamon D, Thiel RP, Luftner D, Ghani F, 2005, Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies. Breast Cancer Res 7(4):R436–R443
McArthur H, 2009, An overview of HER-targeted therapy with lapatinib in breast cancer. Adv Ther 26(3):263–271
Zhou X, Cella D, Cameron D, Amonkar MM, Segreti A, Stein S, Walker M, Geyer CE, 2009, Lapatinib plus capecitabine versus capecitabine alone for HER2+, ErbB2+, metastatic breast cancer: quality-of-life assessment. Breast Cancer Res Treat 117(3):577– 589
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL, 2001, Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874
Barnes DM, Bartkova J, Camplejohn RS, Gullick WJ, Smith PJ, Millis RR, 1992, Overexpression of the c-erbB-2 oncoprotein: why does this occur more frequently in ductal carcinoma in situ than in invasive mammary carcinoma and is this of prognostic significance? Eur J Cancer 28(2–3):644–648
Allred DC, Clark GM, Molina R, Tandon AK, Schnitt SJ, Gilchrist KW, Osborne CK, Tormey DC, McGuireWL, 1992)Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 23(9):974–979
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Clark GM, McGuire WL, 1991, Follow-up study of HER-2/neu amplification in primary breast cancer. Cancer Res 51(3):944–948
Schroeter CA, De Potter CR, Rathsmann K, Willighagen RG, Greep JC, 1992, c-erbB-2 positive breast tumours behave more aggressively in the first years after diagnosis. Br J Cancer 66(4):728–734
Bianchi S, Paglierani M, Zampi G, Cardona G, Cataliotti L, Bonardi R, Ciatto S, 1993, Prognostic significance of c-erbB-2 expression in node negative breast cancer. Br J Cancer 67(3):625– 629
Press MF, Pike MC, Chazin VR, Hung G, Udove JA, Markowicz M, Danyluk J, Godolphin W, Sliwkowski M, Akita R, Paterson MC, Slnmoir DJ, 1993, Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res 53(20):4960–4970
Meijer SL, Wesseling J, Smit VT, Nederlof PM, Hooijer GK, Ruijter H, Arends JW, Kliffen M, van Gorp JM, Sterk L, van de Vijver MJ, 2011, HER2 gene amplification in patients with breast cancer with equivocal IHC results. J Clin Pathol 64(12):1069– 1072
Dowsett M, Hanna WM, Kockx M, Penault-Llorca F, Ruschoff J, Gutjahr T, Habben K, van de Vijver MJ, 2007, Standardization of HER2 testing: results of an international proficiency-testing ring study. Mod Pathol 20(5):584–591
Wludarski SC, Lopes LF, Berto E, Silva TR, Carvalho FM, Weiss LM, Bacchi CE, 2011, HER2 testing in breast carcinoma: very low concordance rate between reference and local laboratories in Brazil. Appl Immunohistochem MolMorphol 19(2):112– 118
Wilking U, Karlsson E, Skoog L, Hatschek T, Lidbrink E, Elmberger G, Johansson H, Lindstrom L, Bergh J, 2011, HER2 status in a population-derived breast cancer cohort: discordances during tumor progression. Breast Cancer Res Treat 125(2):553– 561
Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D, 2010, Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann Oncol 21(6):1254–1261
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 509
EP 513
DI 10.1007/s12253-013-9610-8
PG 5
ER
PT J
AU Kovacs, AK
Kenessey, I
Timar, J
AF Kovacs, Attila Kristof
Kenessey, Istvan
Timar, Jozsef
TI Skin Metastasis of Internal Cancers: A Single Institution Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Skin metastasis; Visceral organs; Regional distribution
ID Skin metastasis; Visceral organs; Regional distribution
AB Skin metastatization of internal cancers are rare and a few studies are available analyzing its clinicopathological features. The reported incidence of skin metastasis is influenced by two factors: the relative proportion of cancers covered by skin in the various cohorts and the large differences in the prevalences of various cancer types. Futhermore, the anatomical distribution of skin metastases of various cancer types is aslo not well known. Therefore we have collected a skin metastasis cohort of biopsy and authopsy cases (n=80) from the archive of our department and analysed its clinicopathologic features. The adjusted skin metastasis prevalence data of various inner cancers indicated that kidney-, lung- and colorectal cancers have a strong positive preference for skin metastatisation while pancreatic cancer has a negative one. We have provided evidences that lower gastrointestinal- and genitourinary cancers preferred infradiaphragmatic skin regions unlike upper gastrointestinal cancers while lung- and kidney cancers preferred supradiaphragmatic regions. We have also detected that ventral skin regional metastasis is slightly more prevalent irrespective of the cancer type. Our study provide the first statistical data for the variations in skin preference of metastatisation among various cancer types as well as for the significant variations in their regional distributions.
C1 [Kovacs, Attila Kristof] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93, 1091 Budapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93, 1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi u. 93, 1091 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM jtimar@gmail.com
CR Brownstein MH, Helwig EB, 1972, Patterns of cutaneous metastasis. Arch Dermatol 105(6):862–868
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Hussein MRA, 2010, Skin metastasis: a pathologist’s perspective. J Cutan Pathol 37(9):1–20
Alcaraz I, Cerroni L, Rutten A, Kutzner H, Requena L, 2012, Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol 34(4):347–393
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 515
EP 520
DI 10.1007/s12253-013-9611-7
PG 6
ER
PT J
AU Wang, M
Zhang, D
Wang, R
Rui, Y
Zhou, J
Wang, R
Zhou, B
Huang, X
Yang, L
Li, Y
Hu, J
Zhou, Z
Sun, X
AF Wang, Mojin
Zhang, Dan
Wang, Rui
Rui, Yuanyi
Zhou, Jin
Wang, Rong
Zhou, Bin
Huang, Xiaoran
Yang, Lie
Li, Yuan
Hu, Jiankun
Zhou, Zongguang
Sun, Xiaofeng
TI A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE A-kinase anchoring proteins 10; Immunohistochemical staining; Western blot; Polymorphism; Colorectal cancer
ID A-kinase anchoring proteins 10; Immunohistochemical staining; Western blot; Polymorphism; Colorectal cancer
AB The cAMP/PKA signalling events regulated by A-kinase anchoring proteins 10 (AKAP10) is involved in tumorigenesis. Previous study showed that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. However, there was no literature reporting the role of AKAP10 in the pathogenesis of colorectal cancer. The aim of the study was to investigate the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. The expression of AKAP10 was determined by immunohistochemical staining (IHC) and western blot assay on colorectal cancer (n=176), adenoma (n=87) and distant normal mucosa (n=72). 176 patients with colorectal cancer were genotyped for AKAP10 2073A/G polymorphism by TaqMan RT-PCR. We found that the positive expression rate of AKAP10 in colorectal cancer (59 %) was significantly higher than those in adenoma (39 %) and distant normal mucosa (42 %) (P=0.004). There was no significant difference between adenoma and distant normal mucosa (P=0.741). Positive AKAP10 staining was correlated with deeper tumor invasion (P<0.001), lymph nodes metastasis (P=0.022), advanced tumor stage (P<0.001) and poorly differentiated degree (P=0.003). Compared with AA genotype (52 %), positive expression of AKAP10 was significantly increased in colorectal cancer patients with the variant (AG+GG) genotypes (68 %, P=0.033). It was concluded that AKAP10 may play an important role in the development and progression of colorectal cancer.
C1 [Wang, Mojin] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Zhang, Dan] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Wang, Rui] Sichuan University, West China Hospital, Department of GastroenterologyChengdu, China.
[Rui, Yuanyi] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Zhou, Jin] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Wang, Rong] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Zhou, Bin] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Huang, Xiaoran] Sichuan University, West China Hospital, Department of PathologyChengdu, China.
[Yang, Lie] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Li, Yuan] West China Hospital, Sichuan University, Institute of Digestive Surgery and State Key Laboratory of Biotherapy, Department of Pediatric SurgeryChengdu, China.
[Hu, Jiankun] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Zhou, Zongguang] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 37 Guo Xue Xiang, 610041 Chengdu, China.
[Sun, Xiaofeng] University of Linkoping, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Division of OncologyLinkoping, Sweden.
RP Zhou, Z (reprint author), Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 610041 Chengdu, China.
EM zhou_767@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 521
EP 527
DI 10.1007/s12253-013-9612-6
PG 7
ER
PT J
AU Xiong, Sw
Lin, Tx
Xu, Kw
Dong, W
Ling, Xh
Jiang, Fn
Chen, G
Zhong, Wd
Huang, J
AF Xiong, Si-wei
Lin, Tian-xin
Xu, Ke-wei
Dong, Wen
Ling, Xiao-hui
Jiang, Fu-neng
Chen, Guo
Zhong, Wei-de
Huang, Jian
TI MicroRNA-335 Acts as a Candidate Tumor Suppressor in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; microRNA-335; Tumor suppressor; Clinicopathological feature; Prognosis
ID Prostate cancer; microRNA-335; Tumor suppressor; Clinicopathological feature; Prognosis
AB MicroRNA-335 (miR-335) acts as a tumor suppressor or a tumor promoter in different human malignancies. However, the involvement of miR-335 in prostate cancer (PCa) is still unclear. The purpose of this study was to investigate the functional and clinical significance of miR-335 in PCa. miR-335 expression in 3 PCa cell lines (LNCaP/DU145/PC3) and in 20 clinical PCa tissues were detected by real-time quantitative reverse transcriptase-PCR compared with corresponding controls. The function of miR-335 was investigated for cell proliferation, invasion and migration in PCa cells transfected with agents containing EGFP-miR-335 expression vector. Additionally, miR-335 expression in 104 clinical PCa tissues was detected by in situ hybridization. Its assocaitions with clinicopathological features and prognosis in patients with PCa were also determined. miR-335 was significantly down-regulated in PCa cell lines than in the normal prostate cell line (P<0.01). With the similar results in vitro, the reduced expression of miR-335 was also found in human PCa tissues comparing with paired adjacent benign prostate tissues (P<0.05). Moreover, the increased expression of miR-335 suppressed cell proliferation, invasion and migration of PCa cell lines in vitro. Turning to its clinical significance, the low expression of miR-335 was significantly associated with high Gleason Score (P=0.04), advanced clinical stage (P=0.04), and positive metastasis (P=0.02), but not with prognosis in PCa patients. Our data demonstrated for the first time the inhibitory effect of miR-335 on cell proliferation and invasion for PCa cells. The loss of this microRNA might be associated with clinical progression of PCa patients.
C1 [Xiong, Si-wei] Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
[Lin, Tian-xin] Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
[Xu, Ke-wei] Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
[Dong, Wen] Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
[Ling, Xiao-hui] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510180 Guangzhou, China.
[Jiang, Fu-neng] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510180 Guangzhou, China.
[Chen, Guo] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510180 Guangzhou, China.
[Zhong, Wei-de] Guangzhou Medical College, First Affiliated Hospital of Guangzhou Medical College, Urology Key Laboratory of Guangdong Province, 510180 Guangzhou, China.
[Huang, Jian] Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
RP Huang, J (reprint author), Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Department of Urology, 510120 Guangzhou, China.
EM Yehjn@yahoo.com.cn
CR Siegel R, Naishadham D, Jemal A, 2012, Cancer statistics, 2012. CA Cancer J Clin 62:10–29
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Dasgupta S, Srinidhi S, Vishwanatha JK, 2012, Oncogenic activation in prostate cancer progression and metastasis: molecular insights and future challenges. J Carcinog 11:4
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Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell’Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM, 2004, MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101:11755–11760
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Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H, 2009, The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun 385:492–496
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 529
EP 537
DI 10.1007/s12253-013-9613-5
PG 9
ER
PT J
AU Pappa, AC
Tsirakis, G
Boula, A
Sfiridaki, A
Psarakis, EF
Alexandrakis, GM
Stathopoulos, NE
AF Pappa, A Constantina
Tsirakis, George
Boula, Anna
Sfiridaki, Aikaterini
Psarakis, E Fotios
Alexandrakis, G Michael
Stathopoulos, N Efstathios
TI The Significance of non Correlation Between Interleukin-8 Serum Levels with Bone Marrow Microvascular Density in Patients with Myeloma Multiple
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myeloma; Cytokines; Bone marrow; Inflammation
ID Myeloma; Cytokines; Bone marrow; Inflammation
AB In multiple myeloma (MM), angiogenesis plays a substantial role in disease progression. Interleukin-8 (IL-8), a pro-inflammatory chemokine with potent pro-angiogenic properties, has been implicated in the pathophysiology of MM. The aim of the study is to measure serum levels of IL- 8 in MM patients and to correlate them with markers of angiogenesis, such as circulating levels of platelet derived growth factor-AB (PDGF-AB) and angiogenin (Ang), and bone marrow microvascular density (MVD). Fifty-three newly diagnosed MM patients, 23 of them, who reached plateau phase after effective treatment and 20 healthy controls, were studied. Serum levels of PDGF-AB, Ang and IL- 8 were measured by ELISA, whereas bone marrow MVD was estimated by immunohistochemical staining of vessels with anti-CD31. All measured parameters were higher in MM patients compared to controls and in increased disease stages. They all also significantly decreased in plateau phase. IL-8 correlated positively with Ang and PDGF-AB, but not with MVD. The circulating levels of IL-8, PDGFAB and Ang are elevated in patients with MM. The lack of correlation between IL-8 with MVD suggests that its levels represent the inflammatory element of MM disease and the participation in angiogenesis process is rather complex with multifactorial mechanisms.
C1 [Pappa, A Constantina] University Hospital of Heraklion, Hematology Department, Knossou Avenue, 71409 Heraklion, Greece.
[Tsirakis, George] University Hospital of Heraklion, Hematology Department, Stavrakia, 71110 Heraklion, Greece.
[Boula, Anna] University Hospital of Heraklion, Hematology Department, Knossou Avenue, 71409 Heraklion, Greece.
[Sfiridaki, Aikaterini] University Hospital of Heraklion, Hematology Department, Knossou Avenue, 71409 Heraklion, Greece.
[Psarakis, E Fotios] University Hospital of Heraklion, Hematology Department, Knossou Avenue, 71409 Heraklion, Greece.
[Alexandrakis, G Michael] University Hospital of Heraklion, Hematology Department, Stavrakia, 71110 Heraklion, Greece.
[Stathopoulos, N Efstathios] Medical School of the University of Crete, Department of Pathology, Stavrakia, 71110 Heraklion, Greece.
RP Alexandrakis, GM (reprint author), University Hospital of Heraklion, Hematology Department, 71110 Heraklion, Greece.
EM alexandm@med.uoc.gr
CR Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC, 2007, Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer 7:585–598
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Tsirakis G, Pappa C, Kanellou P, Stratinaki M, Xekalou A, Psarakis F, Sakellaris G, Alegakis A, Stathopoulos E, Alexandrakis M, 2012, Role of platelet-derived growth factor- AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma. Hematol Oncol 30:131–136
Kastritis E, Roussou M, Michalis M, Gavriatopoulou M, Michalis E, Migkou M, Delimpasi S, Kyrtsonis MC, Gogos D, Liapis K, Charitaki E, Repousis P, Terpos E, Dimopoulos A, 2010, On behalf of the Greek Myeloma Study Group. High levels of serum angiogenic growth factors in patients with AL amyloidosis: comparisons with normal individuals and multiple myeloma patients. Br J Haematol 150:587–591
Tsirakis G, Pappa C, Kaparou M, Katsomitrou V, Xatzivasili A, Alegakis T, Xekalou A, Stathopoulos E, Alexandrakis M, 2011, Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients. Eur J Histochem 55(e21):113–116
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Pappa C, Tsirakis G, Kanellou P, Kaparou M, Stratinaki M, Xekalou A, Alegakis A, Boula A, Stathopoulos E, Alexandrakis M, 2011, Monitoring serum levels ELR + CXC chemokines and the relationship between microvessel density and angiogenic growth factors in multiple myeloma. Cytokine 56:616–620
Alexandrakis MG, Passam FH, Pappa CA, Dambaki C, Sfakiotaki G, Alegakis AK, Kyriakou DS, Stathopoulos E, 2004, Expression of proliferating cell nuclear antigen, PCNA, in multiple myeloma: its relationship to bone marrow microvessel density and other factors of disease activity. Int J Immunopathol Pharmacol 17:49– 56
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Li S, Ibaragi S, Hu GF, 2011, Angiogenin as a molecular target for the treatment of prostate cancer. Curr Canc Ther Rev 7:83–90
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 539
EP 543
DI 10.1007/s12253-013-9614-4
PG 5
ER
PT J
AU Nikuseva-Martic, T
Serman, L
Zeljko, M
Vidas,
Gasparov, S
Zeljko, MH
Kosovic, M
Pecina-Slaus, N
AF Nikuseva-Martic, Tamara
Serman, Ljiljana
Zeljko, Martina
Vidas, Zeljko
Gasparov, Slavko
Zeljko, Marija Hrvojka
Kosovic, Marin
Pecina-Slaus, Nives
TI Expression of Secreted Frizzled-Related Protein 1 and 3, T-cell Factor 1 and Lymphoid Enhancer Factor 1 in Clear Cell Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SFRP1; SFRP3; TCF1; LEF1; cRCC
ID SFRP1; SFRP3; TCF1; LEF1; cRCC
AB Frequency and mortality of renal cell carcinoma (RCC) are increasing for decades. However, the molecular background of RCC tumorigenesis is still poorly understood. In current study we investigated the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC). Thirty-six pairs of paraffinembedded clear cRCC and adjacent nontumoral tissues samples using immunohistochemistry (IHC) were analyzed and compared with corresponding clinicopathological parameters. Immunohistochemistry indicated statistically significant decreased SFRP3 expression in tumor tissues but no consistency in SFRP1 expression in analyzed normal and tumor tissue. The TCF1 expression level was significantly weaker in normal tissue compared to tumor samples while LEF1 protein levels were significantly weaker in tumor tissue. To our knowledge, this is the first report on analysis of the expression of transcription factors TCF1 and LEF1 in clear cell renal cell carcinoma and their comparison with Wnt signal pathway antagonists belonging to SFRP family.
C1 [Nikuseva-Martic, Tamara] University of Zagreb, School of Medicine, Department of Biology, Salata 3, 10000 Zagreb, Croatia.
[Serman, Ljiljana] University of Zagreb, School of Medicine, Department of Biology, Salata 3, 10000 Zagreb, Croatia.
[Zeljko, Martina] “Merkur” University Hospital, Department of Internal MedicineZagreb, Croatia.
[Vidas, Zeljko] “Merkur” University Hospital, Department of UrologyZagreb, Croatia.
[Gasparov, Slavko] “Merkur” University Hospital, Department of Clinical Pathology and CytologyZagreb, Croatia.
[Zeljko, Marija Hrvojka] “Merkur” University Hospital, Department of Internal MedicineZagreb, Croatia.
[Kosovic, Marin] University of Zagreb, School of Medicine, Department of Physics and BiophysicsZagreb, Croatia.
[Pecina-Slaus, Nives] University of Zagreb, School of Medicine, Department of Biology, Salata 3, 10000 Zagreb, Croatia.
RP Nikuseva-Martic, T (reprint author), University of Zagreb, School of Medicine, Department of Biology, 10000 Zagreb, Croatia.
EM tmartic@mef.hr
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Pecina-Slaus N, Nikuseva Martic T, Deak AJ, Zeljko M, Hrascan R, Tomas D, Musani V, 2010, Genetic and protein changes of Ecadherin in meningiomas. J Cancer Res Clin Oncol 136(5):695–702
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 545
EP 551
DI 10.1007/s12253-013-9615-3
PG 7
ER
PT J
AU Perez, OL
Crivaro, A
Barbisan, G
Poleri, L
Golijow, DC
AF Perez, Orlando Luis
Crivaro, Andrea
Barbisan, Gisela
Poleri, Lucia
Golijow, Daniel Carlos
TI XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) Single Nucleotide Polymorphisms in Cervical Cancer Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; HPV; XRCC2; XRCC3; Single Nucleotide Polymorphism
ID Cervical cancer; HPV; XRCC2; XRCC3; Single Nucleotide Polymorphism
AB Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR=2.4 (CI=1.1–4.9, p=0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR=0.48; CI=0.2–1; p=0.1) or XRCC3 241 CT/CC (OR=0.87; CI=0.52–1.4; p=0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.
C1 [Perez, Orlando Luis] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60th and 118th Street, PC B1900 La Plata, Buenos Aires, Argentina.
[Crivaro, Andrea] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60th and 118th Street, PC B1900 La Plata, Buenos Aires, Argentina.
[Barbisan, Gisela] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60th and 118th Street, PC B1900 La Plata, Buenos Aires, Argentina.
[Poleri, Lucia] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60th and 118th Street, PC B1900 La Plata, Buenos Aires, Argentina.
[Golijow, Daniel Carlos] University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), 60th and 118th Street, PC B1900 La Plata, Buenos Aires, Argentina.
RP Perez, OL (reprint author), University of La Plata, Faculty of Veterinary Genetics, IGEVET-CONICET (Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations), PC B1900 La Plata, Argentina.
EM perezlo@gmail.com
CR Wright TC, 2009, Natural history of HPV infections. J Fam Pract 58:3–7
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Huang J, Ye F, Chen H, Lu W, Xie X, 2007, The nonsynonymous single nucleotide polymorphisms of DNA repair gene XRCC1 and susceptibility to the development of cervical carcinoma and high-risk human papillomavirus infection. Int J Gynecol Cancer 17:668–675
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 553
EP 558
DI 10.1007/s12253-013-9616-2
PG 6
ER
PT J
AU Brankovic, SA
Brajuskovic, NG
Mircetic, DJ
Nikolic, ZZ
Kalaba, BP
Vukotic, DV
Tomovic, MS
Cerovic, JS
Radojicic, AZ
Savic-Pavicevic, LD
Romac, PS
AF Brankovic, S Ana
Brajuskovic, N Goran
Mircetic, D Jovan
Nikolic, Z Zorana
Kalaba, B Predrag
Vukotic, D Vinka
Tomovic, M Sasa
Cerovic, J Snezana
Radojicic, A Zoran
Savic-Pavicevic, L Dusanka
Romac, P Stanka
TI Common Variants at 8q24 are Associated with Prostate Cancer Risk in Serbian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Association study; Polymorphism; Single nucleotide polymorphism (SNP); 8q24
ID Prostate cancer; Association study; Polymorphism; Single nucleotide polymorphism (SNP); 8q24
AB Previous studies have shown correlation between single nucleotide polymorphisms (SNPs) at 8q24 and prostate cancer (PCa) risk. This study aimed to evaluate possible association between genotypes and alleles of 8q24 polymorphisms (rs1447295, rs4242382, rs6983267, rs7017300, and rs7837688) and PCa risk and progression. 150 patients with PCa, 150 patients with benign prostatic hyperplasia (BPH), and 100 healthy controls selected from the general population were recruited for this study. SNPs were genotyped by using PCR-RFLP analysis. There was a significant positive association between the A allele of the SNP rs4242382 and PCa risk [PCa vs. BPH comparison, P=0.014 for the best-fitting dominant model; odds ratio (OR) =1.98; 95 % confidence interval (95%CI) 1.14–3.43].We found evidence (P=0.0064) of association between PCa risk and rs7017300 (heterozygote OR= 1.60; 95%CI 0.95–2.69) when comparing genotype distributions in PCa and BPH patients. The association between T allele rs7837688 and PCa riskwas determined in PCa vs. BPH comparison with the best-fitting model of inheritance being log-additive (P=0.0033; OR=2.14, 95%CI 1.27–3.61). Odds ratio for carriers of rs6983267 TT genotype under recessive model of association with PCa was found to be 0.36 (PCa vs. control comparison, P=0.0029; 95%CI 0.19–0.71). For rs1447295, deviation from Hardy-Weinberg equilibrium was observed in BPH patients and controls. We found no association between parameters of PCa progression and five 8q24 SNPs. Locus 8q24 harbors genetic variants associated with PCa risk in Serbian population.
C1 [Brankovic, S Ana] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Brajuskovic, N Goran] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Mircetic, D Jovan] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Nikolic, Z Zorana] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Kalaba, B Predrag] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Vukotic, D Vinka] Clinical Centre, Department of UrologyBelgrade, Serbia.
[Tomovic, M Sasa] Clinical Centre, Clinical Department of SurgeryBelgrade, Serbia.
[Cerovic, J Snezana] Military Medical Academy, Institute of PathologyBelgrade, Serbia.
[Radojicic, A Zoran] University of Belgrade, Faculty of Organizational ScienceBelgrade, Serbia.
[Savic-Pavicevic, L Dusanka] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
[Romac, P Stanka] University of Belgrade, Faculty of BiologyBelgrade, Serbia.
RP Brajuskovic, NG (reprint author), University of Belgrade, Faculty of Biology, Belgrade, Serbia.
EM brajuskovic@bio.bg.ac.rs
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 559
EP 569
DI 10.1007/s12253-013-9617-1
PG 11
ER
PT J
AU Literati-Nagy, Zs
Tory, K
Literati-Nagy, B
Bajza,
Vigh, L
Vigh, L
Mandl, J
Szilvassy, Z
AF Literati-Nagy, Zsuzsanna
Tory, Kalman
Literati-Nagy, Botond
Bajza, Agnes
Vigh, Laszlo
Vigh, Laszlo
Mandl, Jozsef
Szilvassy, Zoltan
TI Synergetic Insulin Sensitizing Effect of Rimonabant and BGP-15 in Zucker-Obes Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rimonabant; BGP-15; Insulin resistance; Obesity; Capsaicin; Glucose clamp
ID Rimonabant; BGP-15; Insulin resistance; Obesity; Capsaicin; Glucose clamp
AB Abdominal obesity is referred for as a common pathogenic root of multiple risk factors, which include insulin resistance, dyslipidemia, hypertension, and a pro-atherogenic and pro-inflammatory state. Irrespective of its psychiatric side effects, rimonabant through blocking cannabinoid-1 receptor (CB1R) induces an increase in whole body insulin sensitivity. The aim of this work was to study the effect of selected doses of another insulin sensitizer compound BGP-15, and rimonabant on insulin resistance in Zucker obese rats with a promise of inducing insulin sensitization together at lower doses than would have been expected by rimonabant alone. We found that BGP-15 potentiates the insulin sensitizing effect of rimonabant. The combination at doses, which do not induce insulin sensitization by themselves, improved insulin signaling. Furthermore our results suggest that capsaicin-induced signal may play a role in insulin sensitizing effect of both molecules. Our data might indicate that a lower dose of rimonabant in the treatment of insulin resistance and type 2 diabetes is sufficient to administer, thus a lower incidence of the unfavorable psychiatric side effects of rimonabant are to be expected.
C1 [Literati-Nagy, Zsuzsanna] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Tory, Kalman] N-Gene Research and Development LtdBudapest, Hungary.
[Literati-Nagy, Botond] Drug Research Center LtdBalatonfured, Hungary.
[Bajza, Agnes] N-Gene Research and Development LtdBudapest, Hungary.
[Vigh, Laszlo] Mecsek Pharma Research LtdPecs, Hungary.
[Vigh, Laszlo] Hungarian Academy of Sciences, Biological Research CenterSzeged, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Szilvassy, Zoltan] University of Debrecen, Department of Pharmacology and Pharmacotherapy, 4032 Debrecen, Hungary.
RP Tory, K (reprint author), N-Gene Research and Development Ltd, Budapest, Hungary.
EM trklmn@gmail.com
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Tim C, Noemi T, Stefano P, Peter L-N, Kalman T, Pierre H, Bernadett K, Linda G, Zsolt T, Gabor B, Imre G, Federica C, Simona C, Ferenc G, Gabor N, Zoltan B, Burcin G, Maria P, Attila G, Akos H, Zsuzsanna L-N, Vigh L Jr, Femke H-B, Andre H, Irma K, Lizette L, Jean-Paul S, Deli Z, Meijering RAM, Henning RH, Brundel BJJM, Kampinga HH, Laszlo K, Zoltan S, Jozsef M, Balazs S, Febbraio MA, Ibolya H, Hooper PL, Laszlo V, 2013, Hydroximic acid derivatives: pleiotrophic HSP coinducers restoring homeostasis and robustness. Curr Pharm Des 19(00)
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 571
EP 575
DI 10.1007/s12253-013-9620-6
PG 5
ER
PT J
AU Kanjer, K
Tatic, S
Neskovic-Konstantinovic, Z
Abu Rabi, Z
Nikolic-Vukosavljevic, D
AF Kanjer, Ksenija
Tatic, Svetislav
Neskovic-Konstantinovic, Zora
Abu Rabi, Zaki
Nikolic-Vukosavljevic, Dragica
TI Treatment Response to Preoperative Anthracycline-Based Chemotherapy in Locally Advanced Breast Cancer: The Relevance of Proliferation and Apoptosis Rates
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breastcancer; Primary chemotherapy; Ki-67; AI; Growth index
ID Breastcancer; Primary chemotherapy; Ki-67; AI; Growth index
AB Objectives were to evaluate the relevance of proliferating fraction (Ki-67) along with apoptotic index (AI) which denoted growth index (Ki-67/AI ratio, GI) to predict pathological response to preoperative chemotherapy, and the pattern of their modifications following chemotherapy in women with locally advanced breast cancer. Archivalmaterial of diagnostic biopsies and surgical specimens from 106 patients were examined. Response rate to chemotherapy in this group was 95 %, eight (8 %) patients achieved a pathological complete remission (pCR) and five (5 %) had a progressive/stable disease (PD/SD). The expression of Ki-67 and AI were assessed using immunohistochemistry and in situ DNA nick labeling assay respectively. Higher baseline level of Ki-67 and GI were associated with an improved pathological response (p=0.0001 and p=0.008), but the degree of correlation with GI was no greater than that with Ki-67 alone. Ki-67 below 1 % highly indicated a lack of tumor response. High AI which characterized the opposite chemo-sensitive tumors, pCR vs. PD/SD (p=0.72) implied that treatment response was not influenced by the "presence" or "absence" of apoptosis. A significant decrease in Ki-67 (p<0.001), AI (p =0.035) and GI (p=0.008) was found following chemotherapy, but percentage change in biomarker values revealed an increase in a number of cases. Higher initial Ki-67 and AI was associated with profound reduction of GI and raising value of GI after treatment, respectively. Such a variance of a given parameter elicited by chemotherapy may have various impact on disease outcome.
C1 [Kanjer, Ksenija] Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Pasterova 14Belgrade, Serbia.
[Tatic, Svetislav] University of Belgrade, Faculty of Medicine, Institute for Pathology, Dr Subotica 1Belgrade, Serbia.
[Neskovic-Konstantinovic, Zora] Institute of Oncology and Radiology of Serbia, Department of Medical Oncology, Pasterova 14Belgrade, Serbia.
[Abu Rabi, Zaki] Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Pasterova 14Belgrade, Serbia.
[Nikolic-Vukosavljevic, Dragica] Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Pasterova 14Belgrade, Serbia.
RP Kanjer, K (reprint author), Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Belgrade, Serbia.
EM ksenijakanjer@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 577
EP 588
DI 10.1007/s12253-013-9621-5
PG 12
ER
PT J
AU Maraz, R
Boross, G
Ambrozay,
Svebis, M
Cserni, G
AF Maraz, Robert
Boross, Gabor
Ambrozay, Eva
Svebis, Mihaly
Cserni, Gabor
TI Selective Ductectomy for the Diagnosis and Treatment of Intraductal Papillary Lesions Presenting with Single Duct Discharge
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intraductal papilloma; Breast cancer; Ductography; Selective ductectomy
ID Intraductal papilloma; Breast cancer; Ductography; Selective ductectomy
AB Solitary ductal papilloma of the breast, although considered a benign disorder has a potential association with carcinomas. We studied and analyzed the role of selective ductectomy (SD) for the diagnosis and treatment of intraductal lesions presenting with single duct discharge and ductography suggestive of intraductal (papillary) lesions. During a ten-year-period, files of patients presenting with single (or rarely dual) duct discharge were retrospectively reviewed. The examinations included mammography, ductography and ultrasonography and cytology of the fluid discharged from the duct in all patients. Patients treated with SD were considered further and their histological diagnosis and treatment were analyzed. The series included 100 patients. In 6 cases malignancy was found in the specimen consisting of four in situ and two invasive ductal carcinomas. These 6 patients had a second operation and this was followed by adjuvant treatment. Nine further patients had atypical ductal hyperplasia in or around papillomas and one patient had lobular neoplasia around her papilloma. In the present series, the incidence of carcinoma associated with the clinical suspicion of papillary lesions was 6%, and further 10% had low grade neoplastic proliferations resulting in the diagnosis of atypical papillomas or atypical ductal hyperplasia or lobular neoplasia around the papilloma, indicating that single duct discharge may be a symptom a malignancy, and that ductal papillomas have malignant potential. For such a low risk and grade of malignancy simple follow-up could be one option, but in some cases SD could be applied to relieve the patients from symptoms and establish a diagnosis.
C1 [Maraz, Robert] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Boross, Gabor] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Ambrozay, Eva] Bacs-Kiskun County Teaching Hospital, Breast Diagnostic UnitKecskemet, Hungary.
[Svebis, Mihaly] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of PathologyKecskemet, Hungary.
RP Maraz, R (reprint author), Bacs-Kiskun County Hospital, Department of Surgery, 6000 Kecskemet, Hungary.
EM marazrobert2010@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 589
EP 595
DI 10.1007/s12253-013-9622-4
PG 7
ER
PT J
AU Zhu, W
Chen, L
Ai, Z
AF Zhu, Wei
Chen, Li
Ai, Zhilong
TI Candidate Agents for Papillary Thyroid Cancer Identified by Gene Expression Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid carcinoma; Differentially expressed genes; Small molecules
ID Papillary thyroid carcinoma; Differentially expressed genes; Small molecules
AB A better understanding of the molecular mechanisms involved in papillary thyroid cancer (PTC) is needed to manage these patients effectively. Our objectives were to expand our understanding of this disease, and to identify biologically active small molecules capable to reverse PTC. We downloaded gene expression data of PTC from Gene Expression Omnibus database and employed computational bioinformatics analysis to compare gene expression patterns with normal tissues. Small molecules that induced inverse gene changes to the PTC were identified. A total of 2,154 differentially expressed genes (DEGs) with a false discovery rate of 0.01 were identified. These 2,154 DEGs were significantly enriched in 17 pathways, including pathways associated with signal transduction, tumorigenesis and lipid or amino acid metabolism. In addition, we identified large amount of small molecules that capable to reverse PTC. We found a group of small molecules that can provide new ideas for the therapeutic studies in PTC. These drugs are clearly a direction that warrants additional consideration.
C1 [Zhu, Wei] Fudan University, Hua Shan Hospital, Department of General Surgery, No.180 Fenglin Road, Xuhui District, 200032 Shanghai, China.
[Chen, Li] Fudan University, Hua Shan Hospital, Department of General Surgery, No.180 Fenglin Road, Xuhui District, 200032 Shanghai, China.
[Ai, Zhilong] Fudan University, Hua Shan Hospital, Department of General Surgery, No.180 Fenglin Road, Xuhui District, 200032 Shanghai, China.
RP Ai, Z (reprint author), Fudan University, Hua Shan Hospital, Department of General Surgery, 200032 Shanghai, China.
EM aizhilongazl@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2013
VL 19
IS 3
BP 597
EP 604
DI 10.1007/s12253-013-9625-1
PG 8
ER
PT J
AU Vuity, D
Bogdan, S
Csurgay, K
Sapi, Z
Nemeth, Zs
AF Vuity, Drazsen
Bogdan, Sandor
Csurgay, Katalin
Sapi, Zoltan
Nemeth, Zsolt
TI Malignant Fibrous Histiocytoma/Undifferentiated High-Grade Pleomorphic Sarcoma of the Maxillary Sinus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Malignant fibrous histiocytoma; Undifferentiated high-grade pleomorphic sarcoma; Orbitoethmoidal spread; Young age; Lymphatic metastasis
ID Malignant fibrous histiocytoma; Undifferentiated high-grade pleomorphic sarcoma; Orbitoethmoidal spread; Young age; Lymphatic metastasis
AB Malignant fibrous histiocytoma (MFH) also known as undifferentiated high-grade pleomorphic sarcoma (UHPS) is a soft tissue sarcoma, composed of undifferentiated mesenchymal tumors possessed fibrohistiocytic morphology without definite true histiocytic differentiation. Head and neck localization is very rare, showing an incidence ranging from 4% to 10% in different series of investigations. The most frequent involved sites in UHPS are the neck and parotid, followed by the scalp, face, anterior skull base and orbit. Upper aerodigestive tract, lateral skull base and ear are rare locations. The incidence of the lymphatic metastases is also rare. The aim of this article is to report a case of UHPS in the maxillary sinus with palatal, orbital and ethmoidal involvement, with lymphatic metastasis and its surgical treatment. In addition, we review the literature of similar cases of the past 12 years.
C1 [Vuity, Drazsen] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Bogdan, Sandor] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Csurgay, Katalin] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Nemeth, Zsolt] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
RP Vuity, D (reprint author), Semmelweis University, Department of Oral and Maxillofacial Surgery, Budapest, Hungary.
EM drazsen@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 605
EP 609
DI 10.1007/s12253-013-9640-2
PG 5
ER
PT J
AU Xie, B
Chen, J
Liu, B
Zhan, J
AF Xie, Biao
Chen, Jinhui
Liu, Bin
Zhan, Junkun
TI Klotho Acts as a Tumor Suppressor in Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Klotho; Insulin/IGF1 axis; Autophagy; Wnt signaling; ROS
ID Klotho; Insulin/IGF1 axis; Autophagy; Wnt signaling; ROS
AB The klotho gene is a classical "aging suppressor" gene. Its roles in the pathology of chronic kidney diseases have been well documented. However, the role of Klotho in tumorigenesis, cancer progression, and prognosis is attracting more and more attention. Recent studies have shown that Klotho participates in the progression of several types of human cancers. Klotho functions as a tumor suppressor by inhibiting insulin/IGF1, p53/p21, and Wnt signaling. Silencing klotho gene expression is mainly mediated through promoter hypermethylation and histone deacetylation in cancer. Klotho has been proposed to take part in cell proliferation, survival, autophagy, and resistance to anti-cancer therapies.
C1 [Xie, Biao] 8th Changsha Hospital, Department of General Surgery, 410015 Changsha, Hunan, China.
[Chen, Jinhui] 8th Changsha Hospital, Department of General Surgery, 410015 Changsha, Hunan, China.
[Liu, Bin] 8th Changsha Hospital, Department of General Surgery, 410015 Changsha, Hunan, China.
[Zhan, Junkun] Central South University, Second Xiangya Hospital, Department of Geriatric Medicine, 410011 Changsha, Hunan, China.
RP Zhan, J (reprint author), Central South University, Second Xiangya Hospital, Department of Geriatric Medicine, 410011 Changsha, China.
EM zhanjunkun@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 611
EP 617
DI 10.1007/s12253-013-9663-8
PG 7
ER
PT J
AU Orosz, E
Ember, I
Gombos, K
Toth, L
Tarpay,
Pap,
Otto, Sz
AF Orosz, Eniko
Ember, Istvan
Gombos, Katalin
Toth, Laszlo
Tarpay, Adam
Pap, Akos
Otto, Szabolcs
TI Alternatives for the Intensive Follow-Up After Curative Resection of Colorectal Cancer. Potential Novel Biomarkers for the Recommendations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Colorectal cancer; Follow-up; New strategy; New biomarkers
ID Colorectal cancer; Follow-up; New strategy; New biomarkers
AB Early diagnosis of recurrence and metastasis of colorectal cancer following surgery of curative intent is of vital importance in terms of survival and quality of life. The consistent implementation of appropriate patient follow-up strategy is therefore essential. Debates over the methodology, evaluation and strategy of follow-up have been known for many years, and continue today. By introducing several follow-up models, the present paper offers different options featuring certain individual, national and international, conceptual and financial aspects. Colorectal cancer is an important public health concern due to its destructive nature and frequency, it is therefore essential to develop new monitoring strategies, involving new biomarkers and extensive clinical validation. Since the recurrence rate is very high in high-risk patients, the improvement of individual patient risk estimates and the utilization of a corresponding follow-up model require broad international co-operation and common practice, along with the determination of optimal levels of evidence.
C1 [Orosz, Eniko] National Institute of Oncology, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Ember, Istvan] University of Pecs, Faculty of Medicine, Department of Public HealthPecs, Hungary.
[Gombos, Katalin] University of Pecs, Faculty of Medicine, Department of Public HealthPecs, Hungary.
[Toth, Laszlo] National Institute of Oncology, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Tarpay, Adam] National Institute of Oncology, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Pap, Akos] National Institute of Oncology, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Otto, Szabolcs] National Institute of Oncology, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
RP Otto, Sz (reprint author), National Institute of Oncology, 1122 Budapest, Hungary.
EM sz.otto@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 619
EP 629
DI 10.1007/s12253-013-9672-7
PG 11
ER
PT J
AU Patki, J
Pawar, SS
AF Patki, M. Jyoti
Pawar, S Sagar
TI HSP90: Chaperone-me-not
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Hsp90; Cancer hallmarks; Hsp90 inhibitors; Tumor selectivity; Client proteins; Inhibitor classes
ID Hsp90; Cancer hallmarks; Hsp90 inhibitors; Tumor selectivity; Client proteins; Inhibitor classes
AB With increasing understanding of the molecular basis of carcinogenesis, its progression and metastasis, the cancer therapy has shifted from empirical approaches to targeting specific molecules that regulate the complex network of signalling pathways for cell survival and proliferation. These include key players in malignant transformation like protein kinases, transcription factors, steroid hormone receptors, cell cycle regulators, signal transduction proteins and regulators of apoptosis. Almost all these proteins depend upon the molecular chaperone Hsp90 for their proper folding, stability and function and thus are a part of the Hsp90 clientele. Dependence of these proteins on Hsp90 makes this chaperone an appealing target for cancer therapeutics. Inhibition of Hsp90 can affect multiple oncogenic pathways simultaneously. Moreover Hsp90 inhibitors selectively kill cancer cells compared to normal cells and cancer cells have greater dependence on Hsp90 for the maintenance of intracellular protein homeostasis. All this has led to a rapid pace discovery of Hsp90 clients as well as chemical inhibitors of Hsp90. The role of hsp90 in cancer, tumor selectivity of Hsp90 inhibitors and the current status of Hsp90 inhibitors are discussed in the present review.
C1 [Patki, M. Jyoti] Padmashree Dr D.Y. Patil University, Department of Biotechnology and Bioinformatics, Sector-15, Plot-50, CBD BelapurNavi Mumbai, India.
[Pawar, S Sagar] University of Mumbai, Chikitsak Samuha’s Patkar-Varde College, Department of Zoology, S.V. Road, Goregaon (W)Mumbai, India.
RP Patki, J (reprint author), Padmashree Dr D.Y. Patil University, Department of Biotechnology and Bioinformatics, Navi Mumbai, India.
EM jyotitope8@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 631
EP 640
DI 10.1007/s12253-013-9675-4
PG 10
ER
PT J
AU Qiang, F
Guangguo, R
Yongtao, H
Dandan, D
Hong, Y
AF Qiang, Fang
Guangguo, Ren
Yongtao, Han
Dandan, Dong
Hong, Yang
TI Multidrug Resistance in Primary Tumors and Metastases in Patients with Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; Lymph node metastasis; Multidrug resistance; Protein expression
ID Esophageal cancer; Lymph node metastasis; Multidrug resistance; Protein expression
AB Studies have demonstrated that radical esophagectomy can significantly prolong disease-free survival and improve the survival rate of patients with T3 or T4 esophageal cancer and lymph node metastasis. Multidrug resistant cancer cells have active efflux mechanisms that prevent the accumulation of chemotherapeutic drugs in the cells. The purpose of this study was to compare the expression of five MDR related proteins between primary tumors in patients with thoracic esophageal squamous cell carcinoma (ESCC) and metastatic cancer in lymph nodes to explore the clinical significance of heterogeneity in MDR metastatic cancer cells. Fifty-four patients with ESCC and lymph node metastasis were included. All patients underwent subtotal esophagectomy and D2/D3 lymph node resection. The expression of lung resistance-related protein (LRP), Pglycoprotein, topoisomerase-II, thymidylate synthase, and glutathione S-transferase P1–1 (GST-π) were determined in the primary tumors and lymph nodes via immunohistochemistry. The expression of LRP was significantly different between the primary tumors and lymph nodes (P=0. 026). No significant differences were found for the other four proteins, and protein expression was not associated with either degree of differentiation or disease stage. It was also found that GST-π was expressed in all patients in both the primary tumors and lymph nodes, suggesting that the design and application of chemotherapeutic protocols capable of reducing GST-π expression may be beneficial for patients with ESCC. Additional research regarding the clinical utility of MDR protein expression in ESCC is warranted to design effective chemotherapeutic protocols.
C1 [Qiang, Fang] Cancer Hospital of Sichuan Province, Department of Thoracic Surgery, No. 55, 4th section of Remin South Rd, 610000 Chengdu, Sichuan province, China.
[Guangguo, Ren] Cancer Hospital of Sichuan Province, Department of Thoracic Surgery, No. 55, 4th section of Remin South Rd, 610000 Chengdu, Sichuan province, China.
[Yongtao, Han] Cancer Hospital of Sichuan Province, Department of Thoracic Surgery, No. 55, 4th section of Remin South Rd, 610000 Chengdu, Sichuan province, China.
[Dandan, Dong] The People’s Hospital of Sichuan Province, Department of PathologyChengdu, China.
[Hong, Yang] The People’s Hospital of Sichuan Province, Department of PathologyChengdu, China.
RP Qiang, F (reprint author), Cancer Hospital of Sichuan Province, Department of Thoracic Surgery, 610000 Chengdu, China.
EM fangqiang111@126.com
CR Wolfard A, Paszt A, Szentpali K et al, 2011, Efficacy and drawbacks of neoadjuvant chemoradiotherapy in squamous cell carcinoma of the thoracic esophagus. Hepatogastroenterology 58:1214– 1219
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Ando N, Kato H, Igaki H et al, 2012, A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5- fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus, JCOG9907). Ann Surg Oncol 19:68–74
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Yamamoto Y, Yamai H, Seike J et al, 2012, Prognosis of esophageal squamous cell carcinoma in patients positive for human epidermal growth factor receptor family can be improved by initial chemotherapy with docetaxel, fluorouracil, and cisplatin. Ann Surg Oncol 19:757–765
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Funke S, Timofeeva M, Risch A et al, 2010, Genetic polymorphisms in GST genes and survival of colorectal cancer patients treated with chemotherapy. Pharmacogenomics 11:33–41
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 641
EP 648
DI 10.1007/s12253-013-9623-3
PG 8
ER
PT J
AU Kaira, K
Toyoda, M
Shino, M
Sakakura, K
Takahashi, K
Tominaga, H
Oriuchi, N
Kanai, Y
Oyama, T
Chikamatsu, K
AF Kaira, Kyoichi
Toyoda, Minoru
Shino, Masato
Sakakura, Koichi
Takahashi, Katsumasa
Tominaga, Hideyuki
Oriuchi, Noboru
Kanai, Yoshikatsu
Oyama, Tetsunari
Chikamatsu, Kazuaki
TI Clinicopathological Significance of L-type Amino Acid Transporter 1 (LAT1) Expression in Patients with Adenoid Cystic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenoid cystic carcinoma; LAT1; CD98; Salivary gland; Prognostic factor
ID Adenoid cystic carcinoma; LAT1; CD98; Salivary gland; Prognostic factor
AB The expression of L-type amino acid transporter 1 (LAT1) is correlated with tumor cell growth and survival. However, the clinicopathological significance of LAT1 expression in adenoid cystic carcinoma (ACC) remains to be elucidated. The aim of this study is to investigate the clinicopathological significance of LAT1 expression in ACC. A total of 30 patients with ACC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, p53, and CD98, and cell proliferation and microvessel density (MVD) were determined by Ki-67 and CD34, respectively. High LAT1 and CD98 expression were observed in 27 % (8/30) and 23 % (7/30) of samples, respectively (p>0.999). The high expression of LAT1 was significantly correlated with cell proliferation (Ki-67) and the cell cycle regulator p53. By univariate analysis, solid histological pattern, maxillary tumor site, LAT1, CD98, Ki-67 and p53 were significantly associated with poor prognosis. Multivariate analysis demonstrated that the high expression of LAT1 was an independent prognostic factor for predicting poor prognosis after surgical resection. LAT1 is a promising clinical marker to predict the outcome after surgery in patients with ACC.
C1 [Kaira, Kyoichi] Gunma University, Graduate School of Medicine, Department of Medicine and Molecular Science, Showa-machi, 371-8511 Maebashi, Gunma, Japan.
[Toyoda, Minoru] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Gunma, Japan.
[Shino, Masato] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Gunma, Japan.
[Sakakura, Koichi] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Gunma, Japan.
[Takahashi, Katsumasa] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Gunma, Japan.
[Tominaga, Hideyuki] Gunma University, Gunma Graduate School of Medicine, Department of Molecular ImagingMaebashi, Gunma, Japan.
[Oriuchi, Noboru] Gunma University, Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear medicineMaebashi, Gunma, Japan.
[Kanai, Yoshikatsu] Osaka University, Graduate School of Medicine, Division of Bio-system PharmacologyOsaka, Japan.
[Oyama, Tetsunari] Gunma University, Graduate School of Medicine, Department of Diagnostic PathologyMaebashi, Gunma, Japan.
[Chikamatsu, Kazuaki] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Gunma, Japan.
RP Kaira, K (reprint author), Gunma University, Graduate School of Medicine, Department of Medicine and Molecular Science, 371-8511 Maebashi, Japan.
EM kkaira1970@yahoo.co.jp
CR Kokemueller H, Eckardt A, Brachvogel P et al, 2004, Adenoid cystic carcinoma of the head and neck-a 20 years experience. Int J Oral Maxillofac Surg 33:25–31
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Kobayashi H, Ishii Y, Takayama T, 2005, Expression of L-type amino acid transporter 1, LAT1, in esophageal carcinoma. J Surg Oncol 90:233–238
Kaira K, Oriuchi N, Imai H et al, 2008, Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer 98:742–748
Nakanishi K, Ogata S, Matsuo H et al, 2007, Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch 451:681–690
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 649
EP 656
DI 10.1007/s12253-013-9624-2
PG 8
ER
PT J
AU Sikalidis, KA
Fitch, DM
Fleming, ESh
AF Sikalidis, K Angelos
Fitch, D Mark
Fleming, E Sharon
TI Diet Induced Obesity Increases the Risk of Colonic Tumorigenesis in Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Obesity; Colon cancer; C57BL/6J; Diet induced obesity; AOM
ID Obesity; Colon cancer; C57BL/6J; Diet induced obesity; AOM
AB A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.
C1 [Sikalidis, K Angelos] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
[Fitch, D Mark] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
[Fleming, E Sharon] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
RP Sikalidis, KA (reprint author), University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, USA.
EM angelos_sikalidis@dfci.harvard.edu
CR Murphy TK, Calle EE, Rodriguez C, Khan HS, Thun MJ, 2000, Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol 152(9):847–854
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 657
EP 666
DI 10.1007/s12253-013-9626-0
PG 10
ER
PT J
AU Huang, GL
Qiu, JH
Li, BB
Wu, JJ
Lu, Y
Liu, XY
He, Z
AF Huang, Guo-Liang
Qiu, Jin-Hua
Li, Bin-Bin
Wu, Jing-Jing
Lu, Yan
Liu, Xing-Yan
He, Zhiwei
TI Prolyl Isomerase Pin1 Regulated Signaling Pathway Revealed by Pin1 +/+ and Pin1 −/− Mouse Embryonic Fibroblast Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pin1; Pathway; Cancer; Immune
ID Pin1; Pathway; Cancer; Immune
AB Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) plays a key role in a number of diseases including cancer and Alzheimer disease. Previous studies have identified a wide range of phosphoproteins as Pin1 substrates. Related pathways were analyzed separately. The aim of this study was to provide a comprehensive picture involving Pin1 regulation. A genome-wide mRNA expression microarray was carried out using the RNA isolation from Pin1 +/+ and Pin1 −/− mouse embryonic fibroblast (MEF) cells. Signaling pathways regulated by Pin1 were analyzed with the utility of KEGG pathway and GO annotation. An expression pattern regulated by Pin1 was revealed. A total of 606 genes, 375 being up-regulated and 231 down-regulated, were differentially expressed when comparing Pin1 +/+ to Pin1 −/− MEF cells. Totally 48 pathways were shown to be regulated by Pin1 expression in KEGG pathway analysis. In the GO annotation system, 19 processes on biological processes, 15 processes on cellular components, and 18 processes on molecular functions were found to be in the regulation of Pin1 expression. Pathways related to immune system and cancer showed most significant association with Pin1 regulation. Pin1 is an important regulator in a wide range of signaling pathways that were related to immune system and cancer.
C1 [Huang, Guo-Liang] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
[Qiu, Jin-Hua] Huizhou First Hospital, Department of Neurology, 516000 Huizhou, China.
[Li, Bin-Bin] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
[Wu, Jing-Jing] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
[Lu, Yan] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
[Liu, Xing-Yan] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
[He, Zhiwei] Guangdong Medical University, Cancer Research Institute, No. 1 Xincheng Road, 523808 Dongguan, China.
RP He, Z (reprint author), Guangdong Medical University, Cancer Research Institute, 523808 Dongguan, China.
EM zhiweihe688@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 667
EP 675
DI 10.1007/s12253-013-9629-x
PG 9
ER
PT J
AU Zhou, L
Qiu, T
Xu, J
Wang, T
Wang, J
Zhou, X
Huang, Z
Zhu, W
Shu, Y
Liu, P
AF Zhou, Li
Qiu, Tianzhu
Xu, Jing
Wang, Tongshan
Wang, Jian
Zhou, Xin
Huang, Zebo
Zhu, Wei
Shu, Yongqian
Liu, Ping
TI miR-135a/b Modulate Cisplatin Resistance of Human Lung Cancer Cell Line by Targeting MCL1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-135a/b; Cisplatin resistance; Apoptosis; MCL1; Lung cancer
ID miR-135a/b; Cisplatin resistance; Apoptosis; MCL1; Lung cancer
AB microRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of drug resistance in human lung cancer cell line. We found that miR-135a/b were downregulated while MCL1 was upregulated in A549/CDDP (cisplatin) cells, compared with the parental A549 cells. In vitro drug sensitivity assay demonstrated that overexpression of miR-135a/b sensitized A549/CDDP cells to cisplatin. The luciferase activity of MCL1 3′-untranslated region-based reporter constructed in A549/CDDP cells suggested that MCL1 was the direct target gene of miR-135a/b. Enforced miR-135a/b expression reduced MCL1 protein level and sensitized A549/CDDP cells to CDDP-induced apoptosis. Taken together, our findings first suggested that hsa-miR-135a/b could play a role in the development of CDDP resistance in lung cancer cell line at least in part by modulation of apoptosis via targeting MCL1.
C1 [Zhou, Li] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Qiu, Tianzhu] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Xu, Jing] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Wang, Tongshan] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Wang, Jian] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Zhou, Xin] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Huang, Zebo] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Zhu, Wei] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Shu, Yongqian] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
[Liu, Ping] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 300 Guangzhou Road, 210029 Nanjing, China.
RP Liu, P (reprint author), Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 210029 Nanjing, China.
EM liu-ping@csco.org.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 677
EP 683
DI 10.1007/s12253-013-9630-4
PG 7
ER
PT J
AU Sun, G
Hu, W
Lu, Y
Wang, Y
AF Sun, Guogui
Hu, Wanning
Lu, Yifang
Wang, Yadi
TI A Meta-Analysis of HIF-1α and Esophageal Squamous Cell Carcinoma (ESCC) Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ESCC; HIF-1α; Meta-analysis; Survival
ID ESCC; HIF-1α; Meta-analysis; Survival
AB To investigate the correlation of hypoxiainducible factor-1α (HIF-1α) expression with clinical prognosis and efficacy of radiochemotherapy in esophageal squamous cell carcinoma (ESCC). Studies assessing the clinical or prognostic significance of HIF-1α expression in ESCC published prior to December 2011 were selected by searching PubMed, EMBASE, Cochrane Library, and (China National Knowledge Infrastructure) CNKI. A metaanalysis was performed to clarify the impact of HIF-1α expression on clinicopathological parameters or survival in ESCC. A total of 16 studies met the inclusion criteria, which included 1261 patients with ESCC. Accordingly, the level of HIF-1α expression in esophageal tissues of patients with ESCC was significantly higher than that in normal patients (odds ratio, OR=33.111, 95 % confidence interval, CI= 11.912–92.040). The expression of HIF-1α correlated with the depth of invasion (OR=1.701, 95 % CI=1.076–4.705), clinical TNM stage (OR=2.160, 95%CI=1.516–3.077), as well as lymph node metastasis (OR=2.393, 95 % CI= 1.319–4.344), regardless of differentiation grading (OR= 1.185, 95 % CI=0.859–1.635). Furthermore, there was a significant association of increased HIF-1α expression with poorer radiochemotherapy outcomes, 2-year overall survival (OR=0.219, 95 % CI=0.104–0.461) and survival (OR= 0.320, 95 % CI=0.115–0.887, P<0.05) in patients with ESCC. In addition, HIF-1α expression correlated with VEGF expression in the ESCCs (OR=4.635, 95%CI= 2.591–8.292). Increased expression of HIF-1α plays an important role in the malignant biology of ESCC resulting in significantly poorer radiochemotherapy outcomes and 2- year overall survival. HIF-1α expression may be a prognostic factor, as well as a potential target for therapy in patients with ESCC.
C1 [Sun, Guogui] Tangshan People’s Hospital, Department of Chemoradiotherapy, 063000 Tangshan, Hebei Province, China.
[Hu, Wanning] Tangshan People’s Hospital, Department of Chemoradiotherapy, 063000 Tangshan, Hebei Province, China.
[Lu, Yifang] Tangshan Workers Hospital, Department of Endocrinology (Section I), 063000 Tangshan, Hebei Province, China.
[Wang, Yadi] The Military General Hospital of Beijing PLA, Department of Radiotherapy, 100700 Beijing, China.
RP Hu, W (reprint author), Tangshan People’s Hospital, Department of Chemoradiotherapy, 063000 Tangshan, China.
EM guogui_sun@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 685
EP 693
DI 10.1007/s12253-013-9631-3
PG 9
ER
PT J
AU Pather, S
Mohamed, Z
McLeod, H
Pillay, K
AF Pather, Sugeshnee
Mohamed, Zainab
McLeod, Heather
Pillay, Komala
TI Large Cell Lymphoma: Correlation of HIV Status and Prognosis with Differentiation Profiles Assessed by Immunophenotyping
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diffuse large B cell lymphoma; Plasmablastic lymphoma; Prognosis; HAART; HIV; CD4; Bcl-2; CD38
ID Diffuse large B cell lymphoma; Plasmablastic lymphoma; Prognosis; HAART; HIV; CD4; Bcl-2; CD38
AB Diffuse large B cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) represent aggressive non- Hodgkin lymphomas, particularly in the setting of HIV infection. Since the introduction of highly active antiretroviral therapy (HAART), recent studies have documented improved survival outcome in patients with AIDS-related lymphomas. This study contributes a South African perspective by correlating the HIV status and prognosis of DLBCL and PBL with differentiation profiles assessed by immunophenotyping. Analysis of the morphologic, immunophenotypic and clinicopathologic features of 52 cases of DLBCL and 9 cases of de novo PBL was performed. The overall survival of patients with PBL was poorer than that of DLBCL (logrank p value 0.002). Despite HAART, the overall survival with DLBCL and HIV infection was significantly poorer than HIV negative patients with DLBCL (p value <0.001). Profound immunosuppression was evident in the HIV positive group as the mean CD4 count was 151 cells/mm3 in DLBCL and 61 cells/mm3 in PBL. HIV positive patients were significantly younger at presentation with greater likelihood of extranodal lymphoma. When Hans’ and Muris’ algorithmic stratification of DLBCL were applied, no statistical significance was demonstrated (p values 0.188 and 0.399 respectively). However, when Bcl-2 expression occurred in germinal center-type DLBCL (Hans’ defined), improved survival was conferred by the germinal center immunophenotype (p value 0.007). The study demonstrates that DLBCL and PBL have significant potential for aggressive behaviour and poor outcome in the setting of profound immunosuppression due to HIV infection. Further studies are required to assess the effect of targeted-immunotherapy (Rituximab) in combination with recent amendment of the South African national antiretroviral treatment guidelines which has created tremendous potential for improved survival in patients with AIDS-related non-Hodgkin B-cell lymphomas.
C1 [Pather, Sugeshnee] University of Cape Town, Groote Schuur Hospital, Division of Anatomical Pathology, National Health Laboratory ServiceCape Town, South Africa.
[Mohamed, Zainab] University of Cape Town, Groote Schuur Hospital, Department of Radiation OncologyCape Town, South Africa.
[McLeod, Heather] University of Cape Town, Groote Schuur Hospital, Division of Anatomical Pathology, National Health Laboratory ServiceCape Town, South Africa.
[Pillay, Komala] University of Cape Town, Red Cross Children’s Hospital, Division of Anatomical Pathology, National Health Laboratory ServiceCape Town, South Africa.
RP Pather, S (reprint author), University of Cape Town, Groote Schuur Hospital, Division of Anatomical Pathology, National Health Laboratory Service, Cape Town, South Africa.
EM Sugeshnee.pather@nhls.ac.za
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 695
EP 705
DI 10.1007/s12253-013-9632-2
PG 11
ER
PT J
AU Skapa, P
Robova, H
Rob, L
Zamecnik, J
AF Skapa, Petr
Robova, Helena
Rob, Lukas
Zamecnik, Josef
TI p16INK4a Immunoprofiles of Squamous Lesions of the Uterine Cervix–Implications for the Reclassification of Atypical Immature Squamous Metaplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine cervix; p16; Cytokeratin 17; Cervical intraepithelial neoplasia; Atypical immature squamous metaplasia; Flat condyloma
ID Uterine cervix; p16; Cytokeratin 17; Cervical intraepithelial neoplasia; Atypical immature squamous metaplasia; Flat condyloma
AB p16INK4a immunoprofiles of non-precancerous and dysplastic squamous cervical lesions were defined and applied to the reclassification of atypical immature squamous metaplasia (AIM). The immunoexpression of cytokeratin 17 (CK 17) in AIM was also evaluated. Totally, 295 cervical cone biopsies representing squamous metaplasia, reactive changes, koilocytosis, flat condyloma, CIN I, CIN II, CIN III and AIM were subjected to p16INK4a immunohistochemistry. AIM cases were analyzed using CK 17 antibody. Typical p16INK4a immunoprofiles for the metaplastic, LSIL/HPV and HSIL phenotypes were recorded and used for the categorization of AIM into particular phenotype groups. Results were correlated with CK 17 immunoexpression. All CIN II and CIN III lesions, all but one case of CIN I and all flat condylomas overexpressed p16INK4a. Other non-precancerous lesions, including koilocytosis, were predominantly negative. Contrary to the sporadic and focal immunostaining, diffuse positivity was associated with the dysplastic features of the lesion. CIN II and CIN III were characterized by a diffuse, strong/weak, full-thickness staining, whereas CIN I showed a heterogeneous diffuse/focal, weak/strong, lower half positivity. One third of AIM lesions may be reclassified as HSIL, one third as LSIL/HPV and one third shows metaplastic phenotype. All AIM cases with metaplastic and LSIL/HPV phenotypes expressed CK 17 diffusely, whereas focal positivity slightly prevailed in AIM with HSIL phenotype. We conclude that p16INK4a immunohistochemistry is a supporting method for the differential diagnosis of cervical lesions, which may be especially useful for the reclassification of AIM. The efficacy of CK 17 immunohistochemistry seems to be controversial for these purposes.
C1 [Skapa, Petr] Charles University and University Hospital Motol, 2nd Medical School, Department of Pathology and molecular medicine, V Uvalu 84, 150 06 Prague, Czech Republic.
[Robova, Helena] University Hospital Motol, Charles University, 2nd Medical School, Department of Obstetrics and Gynecology, V Uvalu 84Prague, Czech Republic.
[Rob, Lukas] University Hospital Motol, Charles University, 2nd Medical School, Department of Obstetrics and Gynecology, V Uvalu 84Prague, Czech Republic.
[Zamecnik, Josef] Charles University and University Hospital Motol, 2nd Medical School, Department of Pathology and molecular medicine, V Uvalu 84, 150 06 Prague, Czech Republic.
RP Skapa, P (reprint author), Charles University and University Hospital Motol, 2nd Medical School, Department of Pathology and molecular medicine, 150 06 Prague, Czech Republic.
EM petr.skapa@lfmotol.cuni.cz
CR McCluggage WG, Walsh MY, Thornton CM, Hamilton PW, Date A, Caughley LM, Bharucha H, 1998, Inter- and intra-observer variation in the histopathological reporting of cervical squamous intraepithelial lesions using a modified Bethesda grading system. Br J Obstet Gynaecol 105(2):206–210
Stoler MH, Schiffman M, 2001, Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 285(11):1500–1505
Carreon JD, ShermanME, GuillenD, Solomon D, Herrero R, Jeronimo J, Wacholder S, Rodriguez AC, Morales J, Hutchinson M, Burk RD, Schiffman M, 2007, CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of populationbased cervical samples. Int J Gynecol Pathol 26(4):441–446
Crum CP, Egawa K, Fu YS, Lancaster WD, Barron B, Levine RU, Fenoglio CM, Richart RM, 1983, Atypical immature metaplasia, AIM). A subset of human papilloma virus infection of the cervix. Cancer 51(12):2214–2219
Geng L, Connolly DC, Isacson C, Ronnett BM, Cho KR, 1999, Atypical immature metaplasia, AIM, of the cervix: is it related to high-grade squamous intraepithelial lesion, HSIL)? Hum Pathol 30(3):345–351
Iaconis L, Hyjek E, Ellenson LH, Pirog EC, 2007, p16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection. Arch Pathol Lab Med 131(9):1343–1349
Duggan MA, Akbari M, Magliocco AM, 2006, Atypical immature cervical metaplasia: immunoprofiling and longitudinal outcome. Hum Pathol 37(11):1473–1481
O’Neill CJ, McCluggage WG, 2006, p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol 13(1):8–15
Branca M, Ciotti M, Santini D, Di Bonito L, Giorgi C, Benedetto A, Paba P, Favalli C, Costa S, Agarossi A, Alderisio M, Syrjanen K, 2004, p16(INK4A, expression is related to grade of CIN and highrisk human papillomavirus but does not predict virus clearance after conization or disease outcome. Int J Gynecol Pathol 23(4):354–365
Martens JE, Arends J, Van der Linden PJ, De Boer BA, Helmerhorst TJ, 2004, Cytokeratin 17 and p63 are markers of the HPV target cell, the cervical stem cell. Anticancer Res 24(2B):771–775
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Regauer S, Reich O, 2007, CK17 and p16 expression patterns distinguish, atypical, immature squamous metaplasia from highgrade cervical intraepithelial neoplasia, CIN III). Histopathology 50(5):629–635
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Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T, 1998, Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Am J Pathol 153(6):1741–1748
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Focchi GR, Silva ID, Nogueira-de-Souza NC, Dobo C, Oshima CT, Stavale JN, 2007, Immunohistochemical expression of p16(INK4A, in normal uterine cervix, nonneoplastic epithelial lesions, and low-grade squamous intraepithelial lesions. J Low Genit Tract Dis 11(2):98–104
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Negri G, Vittadello F, Romano F, Kasal A, Rivasi F, Girlando S, Mian C, Egarter-Vigl E, 2004, p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 445(6):616–620
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Castle PE, SchiffmanM,Wheeler CM, Solomon D, 2009, Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 113(1):18–25
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 707
EP 714
DI 10.1007/s12253-013-9633-1
PG 8
ER
PT J
AU Otrock, KZ
Saab, J
Aftimos, G
Nasr, F
Farhat, SF
Khairallah, S
Abadjian, G
Ghosn, M
Sidani, H
Ibrahim, A
Tawil, A
Ghorra, C
Meguerian, Z
Mokaddem, W
Dayeh, W
Salem, Z
Chahine, G
Bitar, N
Mugharbel, A
Makdessi, J
Khater, Ch
El Hajj, M
Abi Gerges, D
Sfeir, Ch
Kattan, J
Ibrahim, K
Saade, M
Sadek, H
Mahfouz, AR
Kharfan-Dabaja, AM
Zaatari, G
Bazarbachi, A
AF Otrock, K Zaher
Saab, Jad
Aftimos, Georges
Nasr, Fady
Farhat, S Fadi
Khairallah, Saad
Abadjian, Gerard
Ghosn, Marwan
Sidani, Hassan
Ibrahim, Ahmad
Tawil, Ayman
Ghorra, Claude
Meguerian, Zarouhie
Mokaddem, Walid
Dayeh, Walid
Salem, Ziad
Chahine, Georges
Bitar, Nizar
Mugharbel, Anas
Makdessi, Joseph
Khater, Christina
El Hajj, Mirna
Abi Gerges, Dany
Sfeir, Charles
Kattan, Joseph
Ibrahim, Khaled
Saade, Michel
Sadek, Hussein
Mahfouz, A Rami
Kharfan-Dabaja, A Mohamed
Zaatari, Ghazi
Bazarbachi, Ali
TI A Collaborative Nationwide Lymphoma Study in Lebanon: Incidence of Various Subtypes and Analysis of Associations with Viruses
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lymphoma; Incidence; Subtypes; Viruses; EBV; Lebanon
ID Lymphoma; Incidence; Subtypes; Viruses; EBV; Lebanon
AB Incidence of various Hodgkin (HL) and non- Hodgkin lymphoma (NHL) subtypes and association with viruses in Lebanon are not known. We undertook a nationwide study of 272 patients diagnosed with lymphoma in 2007. HL comprised 32.7%(n=89) of cases while NHL represented 67.3 % (n=183). Consistent with the literature, nodular sclerosis was the most predominant HL subtype (n=57/89). Among NHL, B-cell NHL represented 88 % (n=161/183), T-cell NHL 9 % (n=17/183), whereas in 2.7 % it was not classifiable. The B-cell NHL comprised predominantly diffuse large B-cell lymphoma (46 %) and follicular lymphoma (23 %). 81 cases were reviewed by a panel of pathologists with 87.6 % concordance rate. Serology was negative for hepatitis C in 122 tested cases. HIV was positive in 2 cases. Two adult T-cell leukemia/lymphoma were HTLV-I positive. EBV IgG were positive in 88.5 % of cases. 38 EBV seropositive cases [27 NHL (24 B-cell, 3 T-cell) and 11 HL] were studied for EBV genome expression using EBV-encoded RNA (EBER)-in situ hybridization. EBER expression was positive in 8 (21 %) cases (6 HL, 2 T-cell NHL). The distribution of lymphoma subtypes in Lebanon appears similar to that of Western countries. The high rate of EBV positivity in HL and T-cell lymphoma by EBER deserves further investigation.
C1 [Otrock, K Zaher] American University of Beirut Medical Center, Department of Pathology and Laboratory MedicineBeirut, Lebanon.
[Saab, Jad] American University of Beirut Medical Center, Department of Pathology and Laboratory MedicineBeirut, Lebanon.
[Aftimos, Georges] Institut National de PathologieBeirut, Lebanon.
[Nasr, Fady] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Farhat, S Fadi] Hammoud Hospital University Medical CenterSaida, Lebanon.
[Khairallah, Saad] Institut National de PathologieBeirut, Lebanon.
[Abadjian, Gerard] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Ghosn, Marwan] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Sidani, Hassan] Makassed General HospitalBeirut, Lebanon.
[Ibrahim, Ahmad] Makassed General HospitalBeirut, Lebanon.
[Tawil, Ayman] American University of Beirut Medical Center, Department of Pathology and Laboratory MedicineBeirut, Lebanon.
[Ghorra, Claude] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Meguerian, Zarouhie] Saint Georges HospitalBeirut, Lebanon.
[Mokaddem, Walid] Islamic HospitalTripoli, Lebanon.
[Dayeh, Walid] Hammoud Hospital University Medical CenterSaida, Lebanon.
[Salem, Ziad] American University of Beirut Medical Center, Department of Internal Medicine, 6044 Beirut, Lebanon.
[Chahine, Georges] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Bitar, Nizar] Sahel General HospitalBeirut, Lebanon.
[Mugharbel, Anas] Makassed General HospitalBeirut, Lebanon.
[Makdessi, Joseph] Saint Georges HospitalBeirut, Lebanon.
[Khater, Christina] Trad HospitalBeirut, Lebanon.
[El Hajj, Mirna] Saint Georges HospitalBeirut, Lebanon.
[Abi Gerges, Dany] Middle East Institute of HealthBeirut, Lebanon.
[Sfeir, Charles] Saint Georges HospitalAjaltoun, Lebanon.
[Kattan, Joseph] Hotel-Dieu de France University HospitalBeirut, Lebanon.
[Ibrahim, Khaled] Hammoud Hospital University Medical CenterSaida, Lebanon.
[Saade, Michel] Rizk HospitalBeirut, Lebanon.
[Sadek, Hussein] Bekaa General HospitalBekaa, Lebanon.
[Mahfouz, A Rami] American University of Beirut Medical Center, Department of Pathology and Laboratory MedicineBeirut, Lebanon.
[Kharfan-Dabaja, A Mohamed] American University of Beirut Medical Center, Department of Internal Medicine, 6044 Beirut, Lebanon.
[Zaatari, Ghazi] American University of Beirut Medical Center, Department of Pathology and Laboratory MedicineBeirut, Lebanon.
[Bazarbachi, Ali] American University of Beirut Medical Center, Department of Internal Medicine, 6044 Beirut, Lebanon.
RP Bazarbachi, A (reprint author), American University of Beirut Medical Center, Department of Internal Medicine, 6044 Beirut, Lebanon.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 715
EP 722
DI 10.1007/s12253-013-9634-0
PG 8
ER
PT J
AU Madaras, L
Baranyak, Zs
Kulka, J
Szasz, MA
Kovacs, A
Lan, HP
Szekely, B
Dank, M
Nagy, T
Kiss, O
Harsanyi, L
Barbai, T
Kenessey, I
Tokes, AM
AF Madaras, Lilla
Baranyak, Zsuzsanna
Kulka, Janina
Szasz, Marcell Attila
Kovacs, Attila
Lan, Huong Phan
Szekely, Borbala
Dank, Magdolna
Nagy, Tibor
Kiss, Orsolya
Harsanyi, Laszlo
Barbai, Tamas
Kenessey, Istvan
Tokes, Anna Maria
TI Retrospective Analysis of Clinicopathological Characteristics and Family History Data of Early-Onset Breast Cancer: A Single-Institutional Study of Hungarian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Early-onset; Family history
ID Breast cancer; Early-onset; Family history
AB Patients at young age (≤35 years) diagnosed with breast cancer (BC) are considered to have poor prognosis. The aim of the present study was to retrospectively analyse clinicopathological characteristics and prognosis in a group of young BC patients. We included women diagnosed with invasive breast carcinoma younger than/or at the age of 35 years. Between 1999 and 2009, 107 women with earlyonset BC were selected from the database of the 2nd Department of Pathology at Semmelweis University. For clinicopathological comparison, 55 women (36–45 years), 214 women (46–65 years), 110 women (66–75 years) and 58 women (76≤years) were also included in the analysis. Family history, clinicopathological and follow-up data were analysed. The tissue specimens were reviewed for histological type, nuclear grade, and estrogen receptor (ER), progesterone receptor (PgR), Ki67 and HER2 status (IHC4). The mean age in the study group was 31.6 years at the time of diagnosis. Histology showed a high incidence of grade III tumours in this group of patients (67.9 %), while only four cases (3.8 %) were considered grade I. According to the immunohistochemical results, 35.3 % of the study cases were considered as Luminal B (LumB: either being higly proliferative or co-expressing HER2) and 33.3 % as triple negative breast carcinomas (TNBC). The detailed questionnaire related to family history was completed and received in 49/107 cases (45.8 %). Analysis of these data revealed an affected family history of breast or ovarian carcinoma in first and second degree relatives in 51.0 %. A high proportion (52.0 %) of TNBC was observed among young women with a family history of the disease. Survival analysis of the 107 patients showed that 25 (23.3 %) women died until 31 December 2012. No significant difference in survival was detectable considering the regimen of systemic treatment (p=0.188). Regarding clinicopathological parameters, the immunophenotypes, grade, pT and pN values differred substantially between the age groups (p=0.001, for all), and the shortest relapse-free survival was seen among the youngest BC patients. This analysis illustrates that breast cancer arising in young women is characterized by the presence of less favorable subtypes such as LumB and TNBC. The increased proportion of TNBC was especially remarquable in the group of patients presenting with family history of the disease. The fact that a high rate of death occured and no significant difference in OS were notable regarding the scheme of systemic therapies (neoadjuvant vs. adjuvant) highlight the necessity of the development of new treatment strategies.
C1 [Madaras, Lilla] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Baranyak, Zsuzsanna] MH Honvedkorhaz, Sebeszeti OsztalyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kovacs, Attila] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Lan, Huong Phan] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szekely, Borbala] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Nagy, Tibor] Szt. Istvan University, Biotechnics Department, Szent-Gyorgyi Albert u. 4., 2100 Godollo, Hungary.
[Kiss, Orsolya] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Harsanyi, Laszlo] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Barbai, Tamas] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tokes, Anna Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Tokes, AM (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM ta@med.semmelweis-univ.hu
CR Tusnady G, Gaudi I, Rejto L, Kasler M, Szentirmay Z, 2008, Survival chances of hungarian cancer patients in the national cancer registry. Magy Onkol 52:339–349
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 723
EP 729
DI 10.1007/s12253-013-9635-z
PG 7
ER
PT J
AU Kim, HJ
Baek, TH
Yim, SH
Kim, HK
Jeong, SH
Kang, BH
Oh, Ss
Lee, GH
Kim, WJ
Kim, DK
AF Kim, Heon Joo
Baek, Tae-Hwa
Yim, Sun Hyun
Kim, Hyun Kyo
Jeong, Seong-Hoo
Kang, Bum Ho
Oh, Sang-seok
Lee, Gu Hee
Kim, Wha Jae
Kim, Dong Kwang
TI Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Invasive Ductal Carcinoma of the Breast: The Impact on Prognosis and Correlation to Clinicopathologic Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CTHRC1; Immunohistochemistry; Metastasis; Breast cancer
ID CTHRC1; Immunohistochemistry; Metastasis; Breast cancer
AB CTHRC1 has been known as a regulator of collagen expression and cell migration. The aim of this research was to clarify the clinicopathologic significance of CTHRC1 expression in human breast cancer. 22 cases of breast cancer tissues, randomly selected from clinically diagnosed patients, showed a significant increase of CTHRC1 mRNA expression compared to the normal tissue from the same patients using RT-PCR and real-time PCR. Additionally we investigated breast cancers from 189 patients by immunohistochemistry (IHC). A high level of CTHRC1 expression was observed in 111 (58.7 %) out of 189 breast cancer patients and the expression was significantly correlated with histologic grade (P=0.026), nodal status (P<0.001), and TNM pathologic stage (P=0.002). High CTHRC1 expression was associated with a shorter recurrence free survival (P=0.008). Taken together, the results showed that CTHRC1 over-expression was significantly associated with clinicopathological factors of poor prognosis in invasive ductal carcinoma. CTHRC1 could be used as a supplementary prognostic biomarker and a potential therapeutic target in breast cancer.
C1 [Kim, Heon Joo] Eulji University, School of Medicine, Department of Pathology, 301-070 Daejeon, South Korea.
[Baek, Tae-Hwa] Eulji University, School of Medicine, Department of Pathology, 301-070 Daejeon, South Korea.
[Yim, Sun Hyun] Eulji University, School of Medicine, Department of Pathology, 301-070 Daejeon, South Korea.
[Kim, Hyun Kyo] Eulji University, School of Medicine, Preventive Medicine, 301-070 Daejeon, South Korea.
[Jeong, Seong-Hoo] Chonbuk National University, Medical School, Department of Surgery, 560-182 Chonju, South Korea.
[Kang, Bum Ho] Korea Research Institute of Bioscience and Biotechnology, Medical Genomics Research Center, 305-333 Daejeon, South Korea.
[Oh, Sang-seok] Gyeongsang National University, PMBBRC, Division of Applied Life Science (BK21), 660-701 Jinju, South Korea.
[Lee, Gu Hee] Korea Research Institute of Bioscience and Biotechnology, Medical Genomics Research Center, 305-333 Daejeon, South Korea.
[Kim, Wha Jae] Korea Research Institute of Bioscience and Biotechnology, Medical Genomics Research Center, 305-333 Daejeon, South Korea.
[Kim, Dong Kwang] Gyeongsang National University, PMBBRC, Division of Applied Life Science (BK21), 660-701 Jinju, South Korea.
RP Kim, DK (reprint author), Gyeongsang National University, PMBBRC, Division of Applied Life Science (BK21), 660-701 Jinju, South Korea.
EM kdkim88@gnu.ac.kr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 731
EP 737
DI 10.1007/s12253-013-9636-y
PG 7
ER
PT J
AU Wu, K
Hu, G
He, X
Zhou, P
Li, J
He, B
Sun, W
AF Wu, Kemin
Hu, Guohuang
He, Xin
Zhou, Peng
Li, Jian
He, Bin
Sun, Weijia
TI MicroRNA-424-5p Suppresses the Expression of SOCS6 in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; miR-424-5p; SOCS6; ERK1/2 signaling pathway
ID Pancreatic cancer; miR-424-5p; SOCS6; ERK1/2 signaling pathway
AB MicroRNAs (miRNAs) are a group of small noncoding RNA molecules predicted to control the activity of about 30 % of all protein-coding genes in mammals. The expression of microRNA-424-5p (miR-424-5p) has been shown to vary in multiple hematological and solid organ malignancies, such as pancreatic cancer. This study aimed to characterize the function of upregulated miR-424-5p in pancreatic cancer and show how downstream suppressor of cytokine-induced signaling 6 (SOCS6) is negatively regulated by miR-424-5p. MiR-424-5p and SOCS6 expression was detected using quantitative real-time PCR (qRT-PCR) in pancreatic cancer tissues and adjacent non-tumorous ductal epithelium tissues. Luciferase reporter assays were used to assess SOCS6 as a target of miR-424-5p. The downstream effect of SOCS6 was measured by qRT-PCR after miR-424- 5p inhibition and SOCS6 upregulation. The functions of miR- 424-5p in vitro in pancreatic cancer cells were measured by migration and invasion assays and flow cytometry. Results suggested miR-424-5p was significantly upregulated in pancreatic cancer and suppress the expression of SOCS6, and miR-424-5p increased proliferation,migration and invasion of pancreatic cancer cells, while inhibited cell apoptosis. It was concluded that miR-424-5p is frequently upregulated in pancreatic cancer and modulates ERK1/2 signaling pathway by negatively regulating SOCS6.
C1 [Wu, Kemin] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
[Hu, Guohuang] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
[He, Xin] Central South University, Xiangya Hospital, Department of AnesthesiologyChangsha, China.
[Zhou, Peng] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
[Li, Jian] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
[He, Bin] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
[Sun, Weijia] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan Province, China.
RP Sun, W (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, China.
EM sunweijia2010@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 739
EP 748
DI 10.1007/s12253-013-9637-x
PG 10
ER
PT J
AU Zhu, M
Xu, Y
Mao, X
Gao, Y
Shao, L
Yan, F
AF Zhu, Mingchen
Xu, Yijun
Mao, Xuelian
Gao, Yanfang
Shao, Lijia
Yan, Feng
TI Overexpression of Metastasis-Associated in Colon Cancer-1 Associated with Poor Prognosis in Patients with Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MACC1; Immunohistochemistry; Prognosis; Esophageal caner
ID MACC1; Immunohistochemistry; Prognosis; Esophageal caner
AB Recent studies have shown that expression of metastasis-associated in colon cancer-1(MACC1) is observed in different types of cancer and plays an important role in tumor metastasis. However, the expression of MACC1 and its possible role in esophageal cancer remains unknown. In this study, we determined the expression of MACC1 in esophageal cancer by utilizing immunohistochemistry and analyzed the relationship between the expression and esophageal cancer prognosis. Immunohistochemistry results showed that 47 of 85 cancer lesions (55.2 %) were stained positive, and high expression of MACC1 was correlated with the node metastasis and TNM stage (P<0.05). The Kaplan-Meier survival curve showed that patients with high MACC1 expression had significantly reduced overall 5-year survival rates (P=0.004). Cox regression analysis revealed that high expression of MACC1 was associated with increased risk of death (hazard ratio [HR] =2.25) in patients with esophageal cancer. These findings suggested that high expression of MACC1 was correlated with progression and metastasis of esophageal cancer and might serve as a novel prognostic marker for patients with esophageal cancer.
C1 [Zhu, Mingchen] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, Jiangsu, China.
[Xu, Yijun] Nanjing First Hospital & Nanjing Medical University First Hospital, Department of Gastroenterology, 68 Changle Road, 210006 Nanjing, Jiangsu, China.
[Mao, Xuelian] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, Jiangsu, China.
[Gao, Yanfang] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, Jiangsu, China.
[Shao, Lijia] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, Jiangsu, China.
[Yan, Feng] Jiangsu Cancer Hospital, Department of Clinical Laboratory, 42 Baiziting Road, 210009 Nanjing, Jiangsu, China.
RP Yan, F (reprint author), Jiangsu Cancer Hospital, Department of Clinical Laboratory, 210009 Nanjing, China.
EM yanfeng2007@sohu.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 749
EP 753
DI 10.1007/s12253-013-9638-9
PG 5
ER
PT J
AU Cireap, N
Narita, D
AF Cireap, Natalia
Narita, Diana
TI Molecular Profiling of ADAM12 and ADAM17 Genes in Human Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ADAM12; ADAM17; Melanoma; Gene expression; Cytokines
ID ADAM12; ADAM17; Melanoma; Gene expression; Cytokines
AB ADAM12 and ADAM17 proteins belong to a family of transmembrane disintegrin-containing metalloproteinases (ADAMs) involved in the proteins ectodomain shedding and cell-cell and cell-matrix interactions. However, the specific biological functions of ADAMs are still unclear and, until now, these proteins were not investigated yet in melanoma. The aim of this study was to analyze the splicing variants of ADAM12 (L and S) and ADAM17 gene expression in melanoma at transcriptional and translational level in comparison with control (non-tumor) tissues. Taking in account that ADAM17 sheddase is involved in the modulation of TNF-α (tumor necrosis factor alpha), we analyzed also this cytokine in the plasma of the same patients before any treatment, and we compared the results with healthy controls. Quantitative-RT-PCR and immunohistochemistry were used to analyze ADAM12 and ADAM17 genes expression and the analysis of TNF-α expression was carried out in the plasma using ELISA. We demonstrated that ADAM12L splicing variant together with ADAM17 gene are strongly overexpressed in melanomas, whereas ADAM12S, although up-regulated when compared with the non-tumor controls, the difference was not statistically significant. When we compared the levels of expression for the ADAMs genes according to the tumor stage, we observed that all three investigated genes were significantly overexpressed in advanced stage in comparison with early stage melanomas. In the plasma of the same patients, the expression of TNF-α was up-regulated and significantly correlated with the expression of ADAM17 and respectively, with the advanced tumor stage.
C1 [Cireap, Natalia] University of Medicine and Pharmacy, Department of Surgical OncologyTimisoara, Romania.
[Narita, Diana] University of Medicine and Pharmacy, Biochemistry Department, E. Murgu 2, 300041 Timisoara, Romania.
RP Narita, D (reprint author), University of Medicine and Pharmacy, Biochemistry Department, 300041 Timisoara, Romania.
EM diana_narita@yahoo.com;diananarita@umft.ro
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 755
EP 762
DI 10.1007/s12253-013-9639-8
PG 8
ER
PT J
AU Arul, D
Subramanian, P
AF Arul, Duraikannu
Subramanian, Perumal
TI Naringenin (Citrus Flavonone) Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Naringenin; Hepatocellular carcinoma cells; Cell proliferation; Apoptosis
ID Naringenin; Hepatocellular carcinoma cells; Cell proliferation; Apoptosis
AB Search for new substances with antiproliferative activity and apoptosis inducing potential towards HepG2 cells is important since HCC is notoriously resistant to conventional chemotherapy. Dietary phytochemicals with significant anti-proliferative and apoptosis inducing potential are considered as agents promising for cancer therapy. Naringenin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong cytotoxic activity in numerous types of cancer cells. However, the detailed molecular mechanisms of its antiproliferative effects and apoptosis induction are still unclear. In this study, we investigated antiproliferative and apoptosisinducing effect of naringenin in human hepatocellular carcinoma HepG2 cells. Naringenin was shown to inhibit the proliferation of HepG2 cells resulted partly from an accumulation of cells in the G0/G1 and G2/M phase of the cell cycle. Naringenin induced a rapid accumulation of p53, which might account for the naringenin-induced G0/G1 and G2/M phase arrests in Hep G2 cells. In addition, naringenin have been shown to induce apoptosis as evidenced by nuclei damage and increased proportion of apoptotic cells detected by flow cytometry analysis. Naringenin triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, subsequent release of cytochrome C, and sequential activation of caspase-3. Our results showed that naringenin had inhibitory effect on the growth of HepG2 cell line through inhibition of cell proliferation and apoptosis induction. The elucidation of the drug targets of naringenin on inhibition of tumor cells growth should enable further development of naringenin for liver cancer therapy.
C1 [Arul, Duraikannu] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalainagar, 608 002 Tamil Nadu, India.
[Subramanian, Perumal] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalainagar, 608 002 Tamil Nadu, India.
RP Arul, D (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
EM sent.biochem@gmail.com
CR Semela D, Heim M, 2011, Hepatocellular carcinoma. Ther Umsch 68:213–217
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 763
EP 770
DI 10.1007/s12253-013-9641-1
PG 8
ER
PT J
AU Huang, L
Wang, Sh
Li, ShSh
Yang, XM
AF Huang, Li
Wang, Shuang
Li, Shi-Sheng
Yang, Xin-Ming
TI Prognostic Significance of Beclin-1 Expression in Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Beclin-1; Laryngeal squamous cell carcinoma; Metastasis; Prognosis
ID Beclin-1; Laryngeal squamous cell carcinoma; Metastasis; Prognosis
AB Beclin-1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The aim of the present investigation was to analyze the Beclin-1 protein expression and to assess its prognostic significance in tissue of laryngeal squamous cell carcinoma (LSCC). Beclin-1 protein expression in 82 primary laryngeal squamous cell carcinoma and 40 paracarcinoma non-tumor tissue samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients’ outcome. The expression of Beclin-1 in tumor tissues was significantly lower than that in non-tumor tissues (P=0.035). Reduced Beclin-1 expression was significantly correlated with lymph node metastases (P=0.021). Kaplan–Meier survival estimates showed a significant correlation between Beclin-1 expression and patient’s survival rate (log-rank P<0.05).Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P=0.048) and Beclin-1 expression (P=0.029) were statistically significant, independent prognostic factors for LSCC. Our findings suggested that decreased Beclin-1 expression and lymph node metastases, as examined by immunohistochemistry, are both independent biomarker for poor prognosis of patients with LSCC.
C1 [Huang, Li] Sichuan University, West China Hospital, Department of Otolaryngology-Head and Neck Surgery, 37, Guoxue Lane, 610041 Chengdu, China.
[Wang, Shuang] Central South University, The Second XiangYa Hospital, Department of Otolaryngology-Head and Neck Surgery, 410011 Changsha, Hunan, China.
[Li, Shi-Sheng] Central South University, The Second XiangYa Hospital, Department of Otolaryngology-Head and Neck Surgery, 410011 Changsha, Hunan, China.
[Yang, Xin-Ming] Central South University, The Second XiangYa Hospital, Department of Otolaryngology-Head and Neck Surgery, 410011 Changsha, Hunan, China.
RP Yang, XM (reprint author), Central South University, The Second XiangYa Hospital, Department of Otolaryngology-Head and Neck Surgery, 410011 Changsha, China.
EM x16y2003@yahoo.com.cn
CR Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP, 2005, Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 114:806–816
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 771
EP 777
DI 10.1007/s12253-013-9642-0
PG 7
ER
PT J
AU Tastemir-Korkmaz, D
Demirhan, O
Kuleci, S
Hasturk, S
AF Tastemir-Korkmaz, Deniz
Demirhan, Osman
Kuleci, Sedat
Hasturk, Serap
TI There is no Significant Association Between Death Receptor 4 (DR4) Gene Polymorphisms and Lung Cancer in Turkish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Death receptor 4; Polymorphisms
ID Lung cancer; Death receptor 4; Polymorphisms
AB Death receptor 4 (DR4) gene is a candidate tumor supressor gene that has a role in apoptotic pathway. It was reported in literature that polymorphisms in DR4 gene lead to susceptibility to many cancers. In accordance with this information, we aimed to investigate the association between G422A, C626G, A683C and A1322G polymorphisms in DR4 gene and lung cancer. We selected 60 patients with lung cancer (LC) and 30 healthy, sex and age matched volunteers randomly. Four polymorhisms, G422A, C626G, A683C and A1322G, in DR4 gene were analyzed with Polymerase Change Reaction (PCR) – Restriction Fragment Lenght Polymorphism (RFLP) and Amplification Refractory Mutation System (ARMS) techniques in both groups. Our results showed that there are no statistically significances between the patients and controls in terms of the G422A, C626G, A683C and A1322G polymorphisms in DR4 gene (p>0,05). Our findings showed no role of DR4 gene polymorhisms in susceptibility to LC and provide a plausible explanation for DR4 genetic heterogeneity in LC susceptibility.
C1 [Tastemir-Korkmaz, Deniz] Adiyaman University, Vocational School of Health Services, TR-02040 Adiyaman, Turkey.
[Demirhan, Osman] Cukurova University, Faculty of Medicine, Department of Medical Biology and GeneticsAdana, Turkey.
[Kuleci, Sedat] Cukurova University, Faculty of Medicine, Department of Chest DiseasesAdana, Turkey.
[Hasturk, Serap] Acibadem Hospital, Department of Chest DiseasesAdana, Turkey.
RP Tastemir-Korkmaz, D (reprint author), Adiyaman University, Vocational School of Health Services, TR-02040 Adiyaman, Turkey.
EM deniz-tbio@hotmail.com
CR Dechant MJ, Fellenberg J, Scheuerpflug CG, Ewerbeck V, Debatin K-M, 2004, Mutation Analysis of the apoptotic “death-receptors” and the adaptors TRADD and FADD/MORT-1 in osteosarcoma tumor samples and osteosarcoma cell lines. Int J Cancer 109:661– 667
Hazra A, Chamberlain RM, Grossman HB, Zhu Y, Spitz MR, Wu X, 2003, Death receptor 4 and bladder cancer risk. Cancer Res 63:1157–1159
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Martinez-Ferrandis JI, Rodriguez-Lopez R, Milne RL, Gonzalez E, Cebolla E, Chirivella I, Zamora P, Arias JI, Palacios S, Cervantes A, Diez O, Benitez J, Armengod ME, 2007, Polymorphisms in TRAIL receptor genes and risk of breast cancer in Spanish women. Cancer Biomark 3(2):89–93
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Lee SH, Shin MS, Kim HS, Lee HK, Park WS, Kim SY, Lee JH, Han SY, Park JY, Oh RR, Kang CS, Kim KM, Jang JJ, Nam SW, Lee JY, Yoo NJ, 2001, Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin’s lymphoma. Oncogene 20(3):399–403
Ulybina YM, Kuligina ES, Mitiushkina NV, Rozanov ME, Ivantsov AO, Ponomariova DN, Togo AV, Levchenko EV, Shutkin VA, Brenister SI, Devilee P, Zhivotovsky B, Hirvonen A, Imyanitov EN, 2009, Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer. Cancer Lett 278(2):183–191
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Lu G, Bing X, Qi S, Chun L, 2007, Association of DR4 gene polymorphism in Chinese patients with gastroduodenal diseases. Med J Wuhan Univ 28:93–95
Wolf S, Mertens D, Pscherer A, Schroeter P, Winkler D, Grone HJ, Hofele C, Hemminki K, Kumar R, SteineckG,Dohner H, Stilgenbauer S, Lichter P, 2006, Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lumphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer. Int J Cancer 118:1831–1835
Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O’Connell M, Kelley RF, Ashkenazi A, de Vos AM, 1999, Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol Cell 4:563–571
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Fernandez V, Jares P, Bea S, Salaverria I, Guino E, de Sanjose S, Colomer D, Ott G, Montserrat E, Campo E, 2004, Frequent polymorphic changes but not mutations of TRAIL receptors DR4 and DR5 in mantle cell lymphoma and other B-cell lymphoid neoplasms. Haematologica 89:1322–1331
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 779
EP 784
DI 10.1007/s12253-013-9643-z
PG 6
ER
PT J
AU Juasook, A
Aukkanimart, R
Boonmars, Th
Sudsarn, P
Wonkchalee, N
Laummaunwai, P
Sriraj, P
AF Juasook, Amornrat
Aukkanimart, Ratchadawan
Boonmars, Thidarut
Sudsarn, Pakkayanee
Wonkchalee, Nadchanan
Laummaunwai, Porntip
Sriraj, Pranee
TI Tumor-Related Gene Changes in Immunosuppressive Syrian Hamster Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunosuppressive; Cholangiocarcinogenesis; Tumor-related gene; Immunohistochemistry
ID Immunosuppressive; Cholangiocarcinogenesis; Tumor-related gene; Immunohistochemistry
AB The results of a previous study demonstrated that prednisolone enhanced cholangiocarcinogenesis. Therefore, to clarify molecular changes during immunosuppressive cholangiocarcinogenesis, Syrian hamsters were divided into 8 groups: uninfected controls; immunosuppressed Syrian hamsters using prednisolone (P); normal Syrian hamsters administered N-nitrosodimethylamine (ND); immunosuppressed Syrian hamsters administered N-nitrosodimethylamine (NDis); normal Syrian hamsters infected with Opisthorchis viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were used for analysis of tumor-related gene expression and immunohistochemistry through cytokeratin 19 (CK19) and proliferating cell nuclear antigen (PCNA) staining. The tumor-related gene expression results show that CCAis groups at all time points exhibited upregulation of COX-2, IL-6, SOD1, CAT and iNOS and downregulation of p53, which correlated with the predominant expression of CK19 and PCNA in liver tissue. These results suggest that prednisolone enhances cholangiocarcinoma development, which was confirmed by molecular changes.
C1 [Juasook, Amornrat] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Aukkanimart, Ratchadawan] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Boonmars, Thidarut] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Sudsarn, Pakkayanee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Wonkchalee, Nadchanan] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Laummaunwai, Porntip] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Sriraj, Pranee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
RP Boonmars, Th (reprint author), Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
EM boonmars@yahoo.com;bthida@kku.ac.th
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 785
EP 794
DI 10.1007/s12253-013-9645-x
PG 10
ER
PT J
AU Yanamoto, S
Yamada, Shi
Takahashi, H
Kawasaki, G
Ikeda, H
Shiraishi, T
Fujita, Sh
Ikeda, T
Asahina, I
Umeda, M
AF Yanamoto, Souichi
Yamada, Shin-ichi
Takahashi, Hidenori
Kawasaki, Goro
Ikeda, Hisazumi
Shiraishi, Takeshi
Fujita, Shuichi
Ikeda, Tohru
Asahina, Izumi
Umeda, Masahiro
TI Predictors of Locoregional Recurrence in T1-2N0 Tongue Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tongue cancer; Recurrence; Neoadjuvant chemotherapy; Surgical margin
ID Tongue cancer; Recurrence; Neoadjuvant chemotherapy; Surgical margin
AB Locoregional recurrence of oral tongue squamous cell carcinoma (OTSCC) has been considered a poor prognostic entity in terms of survival rate. The purpose of this study was to evaluate the incidence of locoregional recurrence and to identify significant risk factors for locoregional recurrence in early-stage OTSCC. We retrospectively reviewed the records of 58 patients who underwent radical surgery for T1-2N0 OTSCC. The local recurrence and regional recurrence rates were 10.3 % (6/58 patients) and 15.5 % (9/58 patients) in this study, respectively. The survival rate of patients with local recurrence was 66.7 %, which was significantly lower than that (96.2 %) of patients without local recurrence, whereas the survival rates of patients with or without regional recurrence were not significantly difference. Pattern of invasion (POI), neoadjuvant chemotherapy (NAC) and the status of the surgical margin were identified as factors influencing local recurrence. In particular, the status of the deep surgical margin was a high potential independent risk factor. The deep surgical margin was resected closely in many NAC-treated cases, suggesting that NAC may lead to local recurrence and a poor outcome. No efficacy of NAC was observed, suggesting that the standard treatment for early OTSCC is surgery alone.
C1 [Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yamada, Shin-ichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Takahashi, Hidenori] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawasaki, Goro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Ikeda, Hisazumi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Shiraishi, Takeshi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Fujita, Shuichi] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone Metabolism, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Ikeda, Tohru] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone Metabolism, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Asahina, Izumi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral Surgery, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Yanamoto, S (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM syana@nagasaki-u.ac.jp
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Penel N, Fournier C, Lefebvre D, Lefebvre JL, 2005, Multivariate analysis of risk factors for wound infection in head and neck squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical procedures. Oral Oncol 41:294–303
Rahima B, Shingaki S, Nagata M, Saito C, 2004, Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:423–431
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Schwartz GJ, Mehta RH, Wenig BL, Shaligram C, Portugal LG, 2000, Salvage treatment for recurrent squamous cell carcinoma of the oral cavity. Head Neck 22:34–41
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Kaya S, Yilmaz T, Gursel B, Sarac S, Sennaroglu L, 2001, The value of elective neck dissection in treatment of cancer of the tongue. Am J Otolaryngol 22:59–64
Lim YC, Lee JS, Koo BS, Kim SH, Kim YH, Choi EC, 2006, Treatment of contralateral N0 neck in early squamous cell carcinoma of the oral tongue: elective neck dissection versus observation. Laryngoscope 116:461–465
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 795
EP 803
DI 10.1007/s12253-013-9646-9
PG 8
ER
PT J
AU Toth, V
Hatvani, Zs
Somlai, B
Harsing, J
Laszlo, FJ
Karpati, S
AF Toth, Veronika
Hatvani, Zsofia
Somlai, Beata
Harsing, Judit
Laszlo, F Janos
Karpati, Sarolta
TI Risk of Subsequent Primary Tumor Development in Melanoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Survivor; Cancer risk; Subsequent primary tumor
ID Melanoma; Survivor; Cancer risk; Subsequent primary tumor
AB Incidence of subsequent malignant tumor development in 740 patients with primary cutaneous melanoma verified between 2006 and 2010 at the Semmelweis University was studied retrospectively and was compared to data of sex and age matched Hungarian population. The follow-up period was 1499 personyears for the whole group from the diagnosis of index melanoma with an average of 2 years. Standardized incidence rate (SIR) was established as the ratio of observed and expected values. The risk of all subsequent malignancies was 15- and 10-fold higher in males (SIR: 15.42) and in females (SIR: 10.55) with melanoma, than in the general population. The increased cancer risk resulted mainly from the significantly higher skin tumor development: SIR values were 160.39 and 92.64 for additional invasive melanoma and 342.28 and 77.04 for subsequent in situ melanoma in males and females, respectively. Non-melanoma skin cancers also notably contributed to the higher risk, the SIR was elevated in both genders to the same extent (males: 17.12, females: 17.55). The risk was also significantly higher for extracutaneous tumor development like chronic lymphocytic leukemia, colon and kidney cancer (both genders), non-Hodgkin’s lymphoma, cervical cancer (females), and bladder carcinoma (males). These data underline the importance of patient education and the necessity of frequent medical follow up, including a close-up dermatological screening of melanoma survivors for further malignancies.
C1 [Toth, Veronika] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Hatvani, Zsofia] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Harsing, Judit] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Laszlo, F Janos] University of Debrecen, Department of Computer Science, Kassai street 26, 4028 Debrecen, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
RP Toth, V (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM toveroka@yahoo.com
CR Wassberg C, Thorn M, Yuen J, Ringborg U, Hakulinen T, 1996, Second primary cancers in patients with cutaneous malignant melanoma: a population-based study in Sweden. Br J Cancer 73:255–259
Levi F, LaVecchia C, Randimbison L, Te VC, Erler G, 1997, Incidence of invasive cancers following cutaneous malignant melanoma. Int J Cancer Suppl 72:776–779
Wassberg C, Thorn M, Yuen J, Hakulinen T, Ringborg U, 1999, Cancer risk in patients with earlier diagnosis of cutaneous melanoma in situ. Int J Cancer 83:314–317
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Goggins WB, Finkelstein DM, Tsao H, 2001, Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma. Cancer 91:874–880
Schmid-Wendtner MH, Baumert J, Wendtner CM, Plewig G, Volkenandt M, 2001, Risk of second primary malignancies in patients with cutaneous melanoma. Br J Dermatol 145:981–985
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Lens MB, Newton-Bishop JA, 2005, An association between cutaneous melanoma and non-Hodgkin’s lymphoma: pooled analysis of published data with a review. Ann Oncol 16:460–465
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Crocetti E, Guzzinati S, Paci E, Falcini F, Zanetti R, Vercelli M et al, 2008, The risk of developing a second, different, cancer among 14 560 survivors of malignant cutaneous melanoma: a study by AIRTUM, the Italian Network of Cancer Registries). Melanoma Res 18:230–234
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 805
EP 810
DI 10.1007/s12253-013-9647-8
PG 6
ER
PT J
AU Yang, Q
Du, J
Zu, L
AF Yang, Qing
Du, Jun
Zu, Lingling
TI Overexpression of CD73 in Prostate Cancer is Associated with Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; CD73; Immunohistochemistry; Lymph node; Metastasis
ID Prostate cancer; CD73; Immunohistochemistry; Lymph node; Metastasis
AB Prostate cancer is the most common malignancy in men in Europe and North America. At present, it is becoming an increasingly common cancer in China. CD73 (ecto-5′-nucleotidase) is a glycosylphosphatidylinositol (GPI)-linked 70-kDa cell surface enzyme. It is also broadly expressed in many types of tissues. Recent studies have showed that CD73 is widely expressed on malignancies and is up-regulated in cancerous tissues. Consequently, we analyzed the expression of CD73 in prostate cancer tissue. The expression of the CD73 protein was evaluated by Immunohistochemistry staining in 116 tissue specimens. The expression was further examined by quantitative real-time PCR (qRT-PCR) and Western blot in the same set of patients. The intense cell membrane staining for the CD73 protein was observed. The expression of CD73 in lymph node non-metastasizing prostate cancer tissues can be seen at low levels, and is generally undetectable. RT-PCR and Western blot showed that the expression of CD73 in lymph node metastasizing prostate cancer was higher compared with non-metastasizing ones. These results suggest that CD73 could be considered as a relevant-specific target for molecular therapy of prostate cancer metastasis.
C1 [Yang, Qing] Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, Department of Genitourinary Oncology, 300060 Tianjin, China.
[Du, Jun] Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, Department of Genitourinary Oncology, 300060 Tianjin, China.
[Zu, Lingling] Tianjin Medical University General Hospital, Tianjin Lung Cancer InstituteTianjin, China.
RP Yang, Q (reprint author), Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, Department of Genitourinary Oncology, 300060 Tianjin, China.
EM yangqingtj@163.com
CR Ruan Y, YuW, Cheng F et al, 2012, Detection of prostate stem cell antigen expression in human prostate cancer using quantum-dotbased technology. Sensors, Basel, 12(5):5461–5470
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Colgan SP, Eltzschig HK, Eckle T, Thompson LF, 2006, Physiological roles for ecto-5′-nucleotidase, CD73). Purinergic Signal 2(2):351–360
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Lee H, Lin EC, Liu L, Smith JW, 2003, Gene expression profiling of tumor xenografts: in vivo analysis of organ-specific metastasis. Int J Cancer 107(4):528–534
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 811
EP 814
DI 10.1007/s12253-013-9648-7
PG 4
ER
PT J
AU Wang, F
Liu, Y
Zhang, H
AF Wang, Fei
Liu, Yulong
Zhang, Hao
TI Loss of MTSS1 Expression is an Independent Prognostic Factor for Hilar Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cholangiocarcinoma; MTSS1; Immunohistochemistry; Prognosis
ID Cholangiocarcinoma; MTSS1; Immunohistochemistry; Prognosis
AB Metastasis suppressor 1 (MTSS1) is a novel metastasis suppressor gene in a variety of cancers. This study aimed to detect MTSS1 expression in normal and cancerous tissue specimens from Chinese patients with hilarcholangiocarcinoma to determine the association with clinicopathological parameters and survival. Tissue microarrays containing normal and tumor specimens were constructed using paraffin blocks from 61 patients for immunohistochemical analysis of MTSS1 expression. A subgroup of these tissues was verified by Western blot analysis. MTSS1 protein was expressed in 24 of 61 cases (39.3 %) of tumor tissues, compared to that in 22 of 26 (84.6 %) of non-neoplastic bile duct epithelium and in 26 of 26 (100 %) of adjacent normal liver cells. Loss of MTSS1 expression was associated with lymph node metastases of cholangiocelluarcarcinoma and tumor cell de-differentiation. MTSS1 expression inversely associated with tumor recurrence and overall survival of the patients by univariate and multivariate analyses. MTSS1 expression was significantly decreased in human hilarcholangiocarcinoma and lost MTSS1 expression was associated with pooroverall survival and tumor recurrences in cholangiocarcinoma patients. Thus, MTSS1 expression represents an independent predictor for tumor recurrence and overall survival in patients with cholangiocarcinoma.
C1 [Wang, Fei] Eastern Hepatobiliary Hospital, Department of SurgeryShanghai, China.
[Liu, Yulong] the Second Affiliated Hospital of Soochow University, Emergency CenterSuzhou, China.
[Zhang, Hao] Fudan University, Hua Shan Hospital, Department of General Surgery, Wulumuqi Middle Road 12, 200040 Shanghai, China.
RP Zhang, H (reprint author), Fudan University, Hua Shan Hospital, Department of General Surgery, 200040 Shanghai, China.
EM drhao@hotmail.com
CR Ito F, Cho CS, Rikkers LF, Weber SM, 2009, Hilar cholangiocarcinoma: Current management. Ann Surg 250(2):210–218
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Maeno H, Ono T, Yamanoi A, Nagasue N, 2007, Our experiences in surgical treatment for hilar cholangiocarcinoma. Hepatogastroenterology 54(75):669–673
Nixdorf S, Grimm MO, Loberg R, Marreiros A, Russell PJ, Pienta KJ, Jackson P, 2004, Expression and regulation of MIM, Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines. Cancer Lett 215(2):209–220
Utikal J, Gratchev A, Muller-Molinet I, Oerther S, Kzhyshkowska J, Arens N, Grobholz R, Kannookadan S, Goerdt S, 2006, The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylation. Int J Cancer 119(10):2287–2293
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Parr C, Jiang WG, 2009, Metastasis suppressor 1, MTSS1, demonstrates prognostic value and anti-metastatic properties in breast cancer. Eur J Cancer 45(9):1673–1683
Liu K,Wang G, Ding H, Chen Y, Yu G,Wang J Downregulation of metastasis suppressor 1(MTSS1, is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer. BMC Cancer 10:428
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Ma S, Guan XY, Lee TK, Chan KW, 2007, Clinicopathological significance of missing in metastasis B expression in hepatocellular carcinoma. Hum Pathol 38(8):1201–1206
Callahan CA, Ofstad T, Horng L, Wang JK, Zhen HH, Coulombe PA, Oro AE, 2004, MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription. Genes Dev 18(22):2724–2729
Wang D, Zhang H, Fang Z, Yu G: Annexin-1 downregulation is associated with clinical outcome in chinese patients with hilar cholangiocarcinoma. Eur Surg Res 45(3–4):151–157
Liu JH, Song LB, Zhang X, Guo BH, Feng Y, Li XX, Liao WT, Zeng MS, Huang KH, 2008, Bmi-1 expression predicts prognosis for patients with gastric carcinoma. J Surg Oncol 97(3):267–272
Urano N, Fujiwara Y, Doki Y, Tsujie M, Yamamoto H, Miyata H, Takiguchi S, Yasuda T, Yano M, Monden M, 2006, Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric Cancer 9(1):44–49
Tsai HM, Chuang CH, Lin XZ, Chen CY, 2009, Factors relating to the short term effectiveness of percutaneous biliary drainage for hilar cholangiocarcinoma. World J Gastroenterol 15(41):5206–5210
Tsalis K, Vasiliadis K, Kalpakidis V, Christoforidis E, Avgerinos A, Botsios D, Megalopoulos A, Haidich AB, Betsis D, 2007, A single-center experience in the management of Altemeier-Klatskin tumors. J Gastrointestin Liver Dis 16(4):383–389
Ramacciato G, Nigri G, Bellagamba R, Petrucciani N, Ravaioli M, Cescon M, Del Gaudio M, Ercolani G, Di Benedetto F, Cautero N et al, 2010, Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma. Am Surg 76(11):1260–1268
Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Ohge H, Sueda T, 2011, Prognostic factors after surgical resection for intrahepatic, hilar, and distal cholangiocarcinoma. Ann Surg Oncol 18(3):651–658
Li Q, Li HK, Hao XS, 2009, Analysis of the surgical outcome and prognostic factors for hilar cholangiocarcinoma. ZhonghuaWai Ke Za Zhi 47(2):94–97
Kirimlioglu H, Turkmen I, Bassullu N, Dirican A, Karadag N, Kirimlioglu V, 2009, The expression of matrix metalloproteinases in intrahepatic cholangiocarcinoma, hilar, Klatskin tumor), middle and distal extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma: role of matrix metalloproteinases in tumor progression and prognosis. Turk J Gastroenterol 20(1):41–47
Fiorentino M, Altimari A, D’Errico A, Gabusi E, Chieco P, Masetti M, Grigioni WF, 2001, Low p27 expression is an independent predictor of survival for patients with either hilar or peripheral intrahepatic cholangiocarcinoma. Clin Cancer Res 7(12):3994–3999
Thelen A, Scholz A, Benckert C, Schroder M, Weichert W, Wiedenmann B, Neuhaus P, Jonas S, 2008, Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma. J Gastroenterol 43(12):959–966
Nishihara Y, Aishima S, Hayashi A, Iguchi T, Fujita N, Taketomi A, Honda H, Tsuneyoshi M, 2009, CD10+ fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma. Histopathology 55(4):423–431
Bershteyn M, Atwood SX, Woo WM, Li M, Oro AE: MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling. Dev Cell 19(2):270–283.
Bompard G, Sharp SJ, Freiss G, Machesky LM, 2005, Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B. J Cell Sci 118(Pt 22):5393–5403
Lin J, Liu J, Wang Y, Zhu J, Zhou K, Smith N, Zhan X, 2005, Differential regulation of cortactin and N-WASP-mediated actin polymerization by missing in metastasis, MIM, protein. Oncogene 24(12):2059–2066
Mattila PK, Pykalainen A, Saarikangas J, Paavilainen VO, Vihinen H, Jokitalo E, Lappalainen P, 2007, Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism. J Cell Biol 176(7):953–964
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 815
EP 820
DI 10.1007/s12253-013-9649-6
PG 6
ER
PT J
AU Ma, J
Ma, J
Meng, Q
Zhao, ZSh
Xu, Wj
AF Ma, Jie
Ma, Jun
Meng, Qun
Zhao, Zhong-Sheng
Xu, Wen-juan
TI Prognostic Value and Clinical Pathology of MACC-1 and c-MET Expression in Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; MACC-1; c-MET; Progression; Prognosis
ID Gastric cancer; MACC-1; c-MET; Progression; Prognosis
AB This study was to assess the expression of MACC-1 and c-MET in gastric cancer, and to correlate this expression with clinicohistological parameters and patient prognosis. Total RNA was extracted from cancer tissue and adjacent normal mucosa from frozen biopsy specimens of 30 patients with gastric cancer, and MACC-1 expression was assessed by RTPCR. MACC-1 and c-MET protein expression were also assessed in paraffin-embedded tissues obtained from 436 tumor mucosa and 92 normal mucosa specimens by immunohistochemistry. The correlation between MACC-1 and c-MET expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status and vessel invasion) were also evaluated. RT-PCR analysis revealed that MACC-1 expression was significantly higher in cancerous mucosa compared with normal tissue. Immunohistochemical analysis indicated that MACC-1 and c-MET were moderately or strongly expressed in gastric cancer tissue, whereas expression was weak or absent in non-cancer tissue. Expression of MACC-1 or c-MET was significantly associated with larger tumor size, deeper tumor invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distant metastasis and advanced clinical stage. However, only MACC-1 exhibited significantly greater expression in carcinomas from the higher age group. The intensity of MACC-1 and c-MET expression was also positively correlated. Survival analysis of the 436 gastric cancer patients revealed that patients in clinical stages I, II and III exhibiting lower MACC-1 and c-MET expression had a higher 5-year survival rate compared with patients expressing high levels of these proteins. Multivariate analysis revealed that MACC-1 and c-MET may be independent prognostic indexes of gastric carcinoma (P<0.01). Our findings confirm that MACC-1 and c-MET expression is strongly related to gastric cancer stage and degree of malignancy, and is inversely correlated to patient prognosis. Thus, MACC-1 and c-MET may interact to promote tumorigenesis and their expression may be used as independent prognostic markers in gastric cancer.
C1 [Ma, Jie] Zhejiang Provincial People’s Hospital, Department of PathologyHangzhou, Zhejiang, China.
[Ma, Jun] GongShu District People’s Hospital, Department of MedcineHangzhou, Zhejiang, China.
[Meng, Qun] Zhejiang Provincial People’s Hospital, Department of PathologyHangzhou, Zhejiang, China.
[Zhao, Zhong-Sheng] Zhejiang Provincial People’s Hospital, Department of PathologyHangzhou, Zhejiang, China.
[Xu, Wen-juan] Zhejiang Provincial People’s Hospital, Department of PathologyHangzhou, Zhejiang, China.
RP Zhao, ZSh (reprint author), Zhejiang Provincial People’s Hospital, Department of Pathology, Hangzhou, China.
EM zhaozhongsheng1950@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 821
EP 832
DI 10.1007/s12253-013-9650-0
PG 12
ER
PT J
AU Chen, HJ
Yan, HH
Yang, JJ
Chen, ZH
Su, J
Zhang, XCh
Wu, YL
AF Chen, Hua-Jun
Yan, Hong-Hong
Yang, Jin-Ji
Chen, Zhi-Hong
Su, Jian
Zhang, Xu-Chao
Wu, Yi-Long
TI Disease Flare After EGFR Tyrosine Kinase Inhibitor Cessation Predicts Poor Survival in Patients with Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Epidermal growth factor receptor; Tyrosine kinase inhibitor; Cessation; Disease flare
ID Non-small cell lung cancer; Epidermal growth factor receptor; Tyrosine kinase inhibitor; Cessation; Disease flare
AB Available study revealed non-small cell lung cancer (NSCLC) patients faced a risk of disease flare after cessation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There was no data concerning the prognostic value of disease flare. This study aimed to investigate the prevalence of disease flare in a Chinese cohort, and analyzed its prediction to survival. A cohort of 227 NSCLC patients with acquired resistance to EGFR TKI was retrospectively analyzed. Prevalence and clinical features of disease flare after TKI cessation were reviewed. Survival data were analyzed between patients with flare and those without flare. EGFR gene mutations in tumors were detected. Twenty of 227 (8.8 %) patients were determined with disease flare after TKI cessation. The median interval from TKI cessation to disease flare was 7 days (range 3–18). Forty percent of patients complained of deteriorated dyspnea attributable to malignant effusion. Thirty percent of patients had progressive lesions in the brain. After TKI cessation 35 % of flare patients died before challenge of subsequent treatment. No response was observed in 30 % of flare patients undergoing subsequent chemotherapy. When compared with the non-flare group, patients with disease flare demonstrated comparable progression-free survival (10.1 vs. 9.9 months; P=0.973), shorter post-TKI survival (4.1 vs. 6.1 months; P<0.001), and a significantly poor overall survival (16.6 vs. 21.6 months; P=0.002). Disease flare after cessation of EGFR TKI occurred in Chinese NSCLC population and predicted a poor survival.
C1 [Chen, Hua-Jun] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Yan, Hong-Hong] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Yang, Jin-Ji] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Chen, Zhi-Hong] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Su, Jian] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Zhang, Xu-Chao] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
[Wu, Yi-Long] Guangdong General Hospital, Guangdong Lung Cancer InstituteGuangzhou, China.
RP Wu, YL (reprint author), Guangdong General Hospital, Guangdong Lung Cancer Institute, Guangzhou, China.
EM syylwu@live.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 833
EP 838
DI 10.1007/s12253-013-9651-z
PG 6
ER
PT J
AU Menschikowski, M
Hagelgans, A
Schuler, U
Froeschke, S
Rosner, A
Siegert, G
AF Menschikowski, Mario
Hagelgans, Albert
Schuler, Ulrich
Froeschke, Susanne
Rosner, Andrea
Siegert, Gabriele
TI Plasma Levels of Phospholipase A2-IIA in Patients with Different Types of Malignancies: Prognosis and Association with Inflammatory and Coagulation Biomarkers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; Inflammation; Secreted phospholipase A2; C-reactive protein; Fibrinogen
ID Cancer; Inflammation; Secreted phospholipase A2; C-reactive protein; Fibrinogen
AB It is well-known that the plasma level of group IIA phospholipase A2 (sPLA2-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA2-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin’s lymphoma. Plasma levels of sPLA2-IIA are shown to be markedly increased in all types of analysed malignancies in comparison to the normal range (22.8±4.5 μg/L versus <1.9 μg/L). Levels of sPLA2-IIA correlate positively with CRP (p<0.001), fibrinogen (p<0.01), FVIII (p<0.05), and vWF (p<0.05) and negatively with antithrombin levels (p<0.05). Kaplan- Meier analyses revealed a statistically prolonged survival time of patients with lower sPLA2-IIA concentrations (<4 μg/L) in comparison to those with elevated concentrations (>4 μg/L) of this enzyme. In conclusion, the study shows that the measurement of plasma sPLA2-IIA levels has prognostic values in patients with different types of malignancies. The association of sPLA2-IIA levels with CRP, fibrinogen, FVIII, and vWF levels supports the importance of inflammatory processes for the up-regulation of sPLA2-IIA during cancer progression.
C1 [Menschikowski, Mario] Technische Universitat Dresden, Medizinische Fakultat, Institut fur Klinische Chemie und Laboratoriumsmedizin, Fetscherstrasse 74, 01307 Dresden, Germany.
[Hagelgans, Albert] Technische Universitat Dresden, Medizinische Fakultat, Institut fur Klinische Chemie und Laboratoriumsmedizin, Fetscherstrasse 74, 01307 Dresden, Germany.
[Schuler, Ulrich] Technische Universitat Dresden, Medizinische Fakultat, Medizinische Klinik und Poliklinik IDresden, Germany.
[Froeschke, Susanne] Technische Universitat Dresden, Medizinische Fakultat, Medizinische Klinik und Poliklinik IDresden, Germany.
[Rosner, Andrea] Technische Universitat Dresden, Medizinische Fakultat, Medizinische Klinik und Poliklinik IDresden, Germany.
[Siegert, Gabriele] Technische Universitat Dresden, Medizinische Fakultat, Institut fur Klinische Chemie und Laboratoriumsmedizin, Fetscherstrasse 74, 01307 Dresden, Germany.
RP Menschikowski, M (reprint author), Technische Universitat Dresden, Medizinische Fakultat, Institut fur Klinische Chemie und Laboratoriumsmedizin, 01307 Dresden, Germany.
EM Mario.Menschikowski@uniklinikum-dresden.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 839
EP 846
DI 10.1007/s12253-013-9652-y
PG 8
ER
PT J
AU Jia, Z
Wang, K
Zhang, A
Wang, G
Kang, Ch
Han, L
Pu, P
AF Jia, Zhifan
Wang, Kun
Zhang, Anling
Wang, Guangxiu
Kang, Chunsheng
Han, Lei
Pu, Peiyu
TI miR-19a and miR-19b Overexpression in Gliomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; miR-19 expression; Real-time PCR; In situ hybridization; PTEN
ID Glioma; miR-19 expression; Real-time PCR; In situ hybridization; PTEN
AB Astrocytic gliomas are the most common type of human primary brain tumors with poor prognosis. MicroRNAs(miRs) are frequently deregulated in gliomas and play an oncogenic or tumor suppressor role. In our previous study we found that miR-19a and miR-19b were upregulated in malignant glioma cell lines by microRNA array. For further validation of this finding, the expression of miR- 19a and miR-19b was detected by qRT-PCR and in situ hybridization(ISH) in 8 malignant glioma cell lines, 43 freshly resected glioma samples and 75 archival paraffin embedded glioma specimens with different grades of malignancy in the present study. The results demonstrate that miR-19a and miR- 19b are overexpressed in glioma cell lines and astrocytic glioma tissues, and their expression level is positively correlated with tumor grades. Additionally, the tumor suppressor gene PTEN is identified as the target ofmiR-19a and miR-19b by Luciferase assay. It is speculated that miR-19a and miR- 19b may have an oncogenic role in gliomagenesis at least partially via the negative regulation of PTEN and the molecular mechanism of gliomagenesis in which miR 19a and miR- 19b involved should be investigated further.
C1 [Jia, Zhifan] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Wang, Kun] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Zhang, Anling] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Wang, Guangxiu] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Kang, Chunsheng] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Han, Lei] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
[Pu, Peiyu] Tianjin Medical University General Hospital, Department of Neurosurgery, 152 An-Shan Road, 300052 Tianjin, China.
RP Pu, P (reprint author), Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
EM zhfjia@hotmail.com
CR Louis DN, 2006, Molecular pathology of malignant gliomas. Annu Rev Pathol 1:97–117
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 847
EP 853
DI 10.1007/s12253-013-9653-x
PG 7
ER
PT J
AU Gasljevic, G
Lamovec, J
Contreras, AJ
Zadnik, V
Blas, M
Gasparov, S
AF Gasljevic, Gorana
Lamovec, Janez
Contreras, Antonio Juan
Zadnik, Vesna
Blas, Mateja
Gasparov, Slavko
TI HER2 in Gastric Cancer: An Immunohistochemical Study on Tissue Microarrays and the Coressponding Whole-Tissue Sections with a Supplemental Fish Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FISH; Gastric carcinoma; HER2; Immunohistochemistry; TMA; Whole sections
ID FISH; Gastric carcinoma; HER2; Immunohistochemistry; TMA; Whole sections
AB Since focal HER2 expression is an issue in GC, TMA construction from the paraffin-embedded surgicallyobtained tissue may not reflect its real status. The aim of this study was to assess the HER2 status in tissue microarrays (TMAs) and the corresponding whole sections using HercepTest immunohistochemistry (IHC), and to correlate it and to assess the concordance of HER2 IHC and fluorescence in situ hybridization (FISH) in TMAs. Concordance of the HER2 expression status for 302 cases of gastric cancer using 9 paired TMAs was evaluated using a 2-mm core size and 305 corresponding whole sections. Concordance of the IHC and FISH HER2 status was compared. In addition,, the HER2 status was compared to clinicopathological characteristics and patients’ survival. Using the whole-section approach, HER2 over-expression was found in 25.2 % (HER2 3+ 6.6 %, HER2 2+ 18.7 %) of tumours. The overall concordance of IHC between the cores and the whole section was 84.9 %; 15.1 % of the tumours showed HER2 amplification. The overall concordance of IHC and FISH on cores was 75.7 %. The level of amplification correlated with the IHC score. Relationship between the intestinal and papillary types and tumour grade was observed for tumours with over-expression and amplification, whereas tumour location was related only to over-expression. There was a statistically significant difference in the overall survival of the patients, which was related to HER2 amplification. In conclusion, good concordance of the IHC HER2 results between tissue cores in TMA and whole sections, and excellent concordance of the IHC and FISH results on tissue cores was found. At least a part of the observed IHC HER2 heterogeneity could very likely be explained by fixation artifacts.With adequate fixation, a higher concordance of IHC HER2 between the cores and the whole sections can be expected. The TMA approach could enable an easier analysis of more than one representative tumour block.
C1 [Gasljevic, Gorana] Institute of Oncology, Department of Pathology, Zaloska 2, 1000 Ljubljana, Slovenia.
[Lamovec, Janez] Institute of Oncology, Department of Pathology, Zaloska 2, 1000 Ljubljana, Slovenia.
[Contreras, Antonio Juan] Institute of Oncology, Department of Pathology, Zaloska 2, 1000 Ljubljana, Slovenia.
[Zadnik, Vesna] Institute of Oncology, Cancer Registry, Zaloska 2, 1000 Ljubljana, Slovenia.
[Blas, Mateja] Institute of Oncology, Department of Pathology, Zaloska 2, 1000 Ljubljana, Slovenia.
[Gasparov, Slavko] “Merkur” University Hospital, Department of Clinical Pathology and Cytology, Zajceva 19, 10 000 Zagreb, Croatia.
RP Gasljevic, G (reprint author), Institute of Oncology, Department of Pathology, 1000 Ljubljana, Slovenia.
EM ggasljevic@onko-i.si
CR Kamangar F, Dores GM, Anderson WF, 2006, Patterns of cancer incidence, mortality and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150
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Faycal J, Bessaguet C, Nousbaum JB et al, 2005, Epidemiology and long term survival of gastric carcinoma in the French district of Finestere between 1984 and 1995. Gastroenterol Clin Biol 29:23–32
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Hofmann M, Stoss O, Shi D et al, 2008, Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 855
EP 865
DI 10.1007/s12253-013-9654-9
PG 11
ER
PT J
AU Sikalidis, KA
Fitch, DM
Fleming, ESh
AF Sikalidis, K Angelos
Fitch, D Mark
Fleming, E Sharon
TI Risk of Colonic Cancer is Not Higher in the Obese Lepob Mouse Model Compared to Lean Littermates
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Leptin; Aberrant crypts; Tumors; Proliferation; Azoxymethane
ID Leptin; Aberrant crypts; Tumors; Proliferation; Azoxymethane
AB Epidemiological data suggest that obesity increases the risk of colorectal cancer in humans. Given that diet-induced obesity mouse models verified the epidemiological data, the present study aimed to determine whether obese C57BL/6J-Lepob male mice (a different obesity in vivo model) were at greater risk of colonic cancer than their lean male littermates. Risk of colonic tumorigenesis was assessed by numbers of aberrant crypts, aberrant crypt foci and colonic tumors. Proliferation of the colonic epithelia was assessed histochemically following administration of BrdU. Availability of the procarcinogen, azoxymethane (AOM) to target tissues was assessed by quantifying via HPLC plasma AOM concentrations during the 60 min period following AOM injection. When obese and lean mice were injected with azoxymethane (AOM) at doses calculated to provide equivalent AOM levels per kg lean body mass, obese animals had significantly fewer aberrant crypts/colon and fewer aberrant crypt foci/colon than the lean animals. Tumors were identified in the colonic mucosa of lean (4 tumors in 14 mice) but not obese (0 tumors in 15 mice) mice. Colonic cell proliferation was not significantly different for obese and lean mice. Because these results were unexpected, plasma AOM concentrations were measured and were found to be lower in the obese than lean mice. When plasma AOM levels were comparable for the lean and obese mice, the Lepob mice continued to have significantly fewer aberrant crypt foci/colon than the lean mice, but differences were not statistically different for aberrant crypts/colon. Interestingly, obese Lepob mice did not exhibit increased risk of colonic cancer as expected. Instead, Lepob mice exhibited equivalent or lower risk of colon cancer when compared to the lean group. These results taken together with in vivo results from diet-induced obesity studies, imply that leptin may be responsible for the increased risk of colon cancer associated with obesity.
C1 [Sikalidis, K Angelos] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
[Fitch, D Mark] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
[Fleming, E Sharon] University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, CA, USA.
RP Sikalidis, KA (reprint author), University of California, Department of Nutritional Sciences and Toxicology, 94720 Berkeley, USA.
EM angelos_sikalidis@dfci.harvard.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 867
EP 874
DI 10.1007/s12253-013-9656-7
PG 8
ER
PT J
AU Bubis, G
Hilly, O
Bubis, R
Halpern, M
Schwartz, A
Koren, R
Rath-Wolfson, L
AF Bubis, Golan
Hilly, Ohad
Bubis, Roy
Halpern, Marisa
Schwartz, Ariel
Koren, Rumelia
Rath-Wolfson, Lea
TI A New Ki-67 / E-Cadherin Cocktail Reduces Inter-observer Variation of the Calculated Proliferative Index
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE Ki-67; E-Cadherin; Cocktail immunostain; Proliferative index; Infiltrating duct carcinoma of breast
ID Ki-67; E-Cadherin; Cocktail immunostain; Proliferative index; Infiltrating duct carcinoma of breast
AB The proliferative index in breast carcinoma is usually calculated by the percentage of the Ki-67 positive cells out of the total number of malignant cells. In order to reduce the inter-observer variability of the calculated proliferative index a cocktail of antibodies against E-Cadherin and Ki-67 (Ki/Cad Cocktail) is presented. The cocktailwas applied on 59 cases of infiltrating duct carcinoma of breast and compared to the consecutive slides stained for Ki-67 alone. The Ki/Cad cocktail has the advantage that by adding the anti E-Cadherin antibody, all the malignant epithelial cells are highlighted and can be differentiated from other proliferating cells. Statistical analysis proved that the cocktail increases the inter-observer agreement from 89 % to 97 % as compared to the Ki-67 alone and also reduces the overlap between the cancer grades.
C1 [Bubis, Golan] Hadassah University, Department of BiologyJerusalem, Israel.
[Hilly, Ohad] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck SurgeryTel Aviv, Israel.
[Bubis, Roy] Tel-Aviv University, Raymond and Beverly School of Physics and AstronomyTel Aviv, Israel.
[Halpern, Marisa] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Schwartz, Ariel] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Koren, Rumelia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Rath-Wolfson, Lea] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
RP Hilly, O (reprint author), Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of Otolaryngology-Head and Neck Surgery, Tel Aviv, Israel.
EM hillyo@clalit.org.il
CR DeSantis C, Siegel R, Bandi P, Jemal A, 2011, Breast cancer statistics, 2011. CA Cancer J Clin 61:409–418., DOI 10.3322/caac.20134
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Assersohn L, Salter J, Powles TJ, A’hern R, Makris A, Gregory RK, Chang J,DowsettM(2003, Studies of the potential utility ofKi67 as a predictive molecular marker of clinical response in primary breast cancer. Breast Cancer Res Treat 82:113–123
Urruticoechea A, Smith IE, Dowsett M, 2005, Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 23:7212–7220
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Gal R, Halpern M, Gertzmann H, Schwartz A, Rath-Wolfson L, Koren R, 2011, Ki-67 & E-Cadherin cocktail: an immunochemical stain for accurate estimation of the proliferative index in infiltrating duct carcinoma of breast. Med Con 4:9–11
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Qureshi HS, Linden MD, Divine G, Raju UB, 2006, E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters. Am J Clin Pathol 125:377–385
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2013
VL 19
IS 4
BP 875
EP 879
DI 10.1007/s12253-013-9655-8
PG 5
ER
PT J
AU Robert, M
Robert, L
AF Robert, A. Matthieu
Robert, Ladislas
TI Xanthine Oxido-Reductase, Free Radicals and Cardiovascular Disease. A Critical Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Xanthine oxidase; Free radicals; ROS; Cardiovascular disease; Allopurinol
ID Xanthine oxidase; Free radicals; ROS; Cardiovascular disease; Allopurinol
AB Free radical mediated pathologies occupy a special place in medical semiology and in mechanistic interpretation of diseases. Free radicals, or better reactive oxygen species (ROS) or reactive nitrogen species (RNS) play also an important role in cell signaling. This is the basis of the ambivalent (Jekyll – Hyde) situation of ROS in biology and pathology. Aging itself is attributed by a popular theory to free radicals. A number of ROS – scavenging substances and procedures were described without however reaching credibility for their therapeutic value. An interesting exception is the xanthine oxido - reductase produced ROS and their role in cardiovascular disease. Allopurinol inhibition of xanthine oxido – reductase was shown to be efficient in some cases of cardiovascular diseases. Another important aspect of xanthine oxido – reductase produced ROS is their antibacterial capacity considered to be of importance with newborns fed on milk rich in this enzyme as well as at the gastrointestinal barrier. This ambivalent role of xanthine oxido – reductase justifies this review on the basic enzymatic mechanisms involved, derived ROS production, their role in the abovementioned biological processes and especially the interest of the inhibition of this enzyme as a preventive or curative measure in some cardiovascular pathologies.
C1 [Robert, A. Matthieu] Hopital Hotel Dieu, Laboratoire de Recherche Ophtalmologique, 7 rue Jean-Baptiste Lully, 94440 Paris, France.
[Robert, Ladislas] Hopital Hotel Dieu, Laboratoire de Recherche Ophtalmologique, 7 rue Jean-Baptiste Lully, 94440 Paris, France.
RP Robert, L (reprint author), Hopital Hotel Dieu, Laboratoire de Recherche Ophtalmologique, 94440 Paris, France.
EM lrobert5@orange.fr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 1
EP 10
DI 10.1007/s12253-013-9698-x
PG 10
ER
PT J
AU Bittner, N
Ostoros, Gy
Geczi, L
AF Bittner, Nora
Ostoros, Gyula
Geczi, Lajos
TI New Treatment Options for Lung Adenocarcinoma - in View of Molecular Background
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Non-small cell lung cancer (NSCLC); Adenocarcinoma; Targeted therapies; Signal transduction pathway; Tyrosine kinase inhibitors; Monoclonal antibodies; EGFR mutation; KRAS; EML-4ALK; VEGFR
ID Non-small cell lung cancer (NSCLC); Adenocarcinoma; Targeted therapies; Signal transduction pathway; Tyrosine kinase inhibitors; Monoclonal antibodies; EGFR mutation; KRAS; EML-4ALK; VEGFR
AB Lung cancer is the leading cause of cancer related mortality all over the world, and a number of developments have indicated future clinical benefit recently. The development of molecular pathology methods has become increasingly important in the prediction of chemotherapy sensitivity and mutation analysis to identify driver mutations as important targets of new therapeutic agents. The most significant changes in the treatment of NSCLC revealed in new pathologic classification and in the introduction of molecularly targeted therapies, which include monoclonal antibodies and small molecule tyrosine kinase inhibitors. The side effects of these agents are generally better tolerated than those of conventional chemotherapy and show higher efficacy. The most important factor follows: histology subtypes, gene mutation status, patients’ selection, drug toxicities and occurence of drug resistance. In the advanced disease, the hope of cure is less than 3 %, but improvements in survival have been clearly achieved. Some years ago the median lung cancer survival rate was 10–12 months, now in case of available specific molecular targets, a significant increase in median survival rates to 24–36 months has been achieved. These agents give an opportunity to provide a new standard of care. Therefore testing EGFR mutations and ALK rearrangements in patients with advanced lung adenocarcinoma should be incorporated into routine clinical practice. This review focuses on the rationale for targeted agents and new treatment possibilities in case of advanced lung adenocarcinoma.
C1 [Bittner, Nora] National Institute of OncologyBudapest, Hungary.
[Ostoros, Gyula] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Geczi, Lajos] National Institute of OncologyBudapest, Hungary.
RP Bittner, N (reprint author), National Institute of Oncology, Budapest, Hungary.
EM nora_bittner@yahoo.ca
CR Travis WD, Brambilla E et al, 2011, International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thoracic Oncol 6:2244–2285
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 11
EP 25
DI 10.1007/s12253-013-9719-9
PG 15
ER
PT J
AU Gao, D
Li, Sh
AF Gao, Dongwei
Li, Sha
TI Stimuli-induced Organ-specific Injury Enhancement of Organotropic Metastasis in a Spatiotemporal Regulation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Stimuli; Organ-specific injury; Organotropic metastasis; Spatiotemporal regulation
ID Stimuli; Organ-specific injury; Organotropic metastasis; Spatiotemporal regulation
AB The relationship between inflammation and tumorigenesis has been established. Recently, inflammation is also reported to be a drive force for cancer metastasis. Further evidences show that various stimuli directly induced-injury in a specific organ can also promote metastasis in this organ, which include epidemiological reports, clinical series and experimental studies. Each type of cancer has preferential sites for metastasis, which is also due to inflammatory factors that are released by primary cancer to act on these sites and indirectly induce injuries on them. Host factors such as stress,fever can also influence distant metastasis in a specific site through stimulation of immune and inflammatory effects. The five aspects support an idea that specific-organ injury directly induced by various stimuli or indirectly induced by primary tumor or host factors activation of proinflammatory modulators can promote metastasis in this organ through a spatiotemporal regulation, which has important implications for personalized prediction, prevention and management of cancer metastasis.
C1 [Gao, Dongwei] 536 Hospital of PLA, 29# Xiadu street, 810007 Xining, Qinghai Province, China.
[Li, Sha] Lanzhou General Hospital of PLA, Department of Radiation Oncology, 333# Southern Binhe Road, 730050 Lanzhou, Gansu Province, China.
RP Gao, D (reprint author), 536 Hospital of PLA, 810007 Xining, China.
EM gdw3152007@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 27
EP 42
DI 10.1007/s12253-013-9734-x
PG 16
ER
PT J
AU Zhang, XM
Ma, ZW
Wang, Q
Wang, JN
Yang, JW
Li, XD
Li, H
Men, TY
AF Zhang, Xiao-Ming
Ma, Zhong-Wei
Wang, Qiang
Wang, Jian-Ning
Yang, Ji-Wei
Li, Xian-Duo
Li, Hao
Men, Tong-Yi
TI A New RNA-Seq Method to Detect the Transcription and Non-coding RNA in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; RNA-seq; Transcription; Non-coding RNA; lncRNA
ID Prostate cancer; RNA-seq; Transcription; Non-coding RNA; lncRNA
AB Prostate cancer is a big killer in many regions especially American men, and this year, the diagnosed rate rises rapidly.We aimed to find the biomarker or any changing in prostate cancer patients. With the development of next generation sequencing, much genomic alteration has been found. Here, basing on the RNA-seq result of human prostate cancer tissue, we tried to find the transcription or non-coding RNA expressed differentially between normal tissue and prostate cancer tissue. 10 T sample data is the RNA-seq data for prostate cancer tissue in this study, we found the differential gene is TFF3-Trefoil factor 3, which was more than seven fold change from prostate cancer tissue to normal tissue, and the most outstanding transcript is C15orf21. Additionally, 9 lncRNAs were found according our method. Finally, we found the many important non-coding RNA related to prostate cancer, some of them were long non-coding RNA (lncRNA).
C1 [Zhang, Xiao-Ming] Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, No.16766 Jingshi Road, 250014 Jinan, Shandong Province, China.
[Ma, Zhong-Wei] Hospital of Shandong Aluminum Corporation, Department of Urology, 255069 Zibo, China.
[Wang, Qiang] 309 Hospital of the Chinese People’s Liberation Army, Department of Urology, 100091 Beijing, China.
[Wang, Jian-Ning] Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, No.16766 Jingshi Road, 250014 Jinan, Shandong Province, China.
[Yang, Ji-Wei] Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, No.16766 Jingshi Road, 250014 Jinan, Shandong Province, China.
[Li, Xian-Duo] Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, No.16766 Jingshi Road, 250014 Jinan, Shandong Province, China.
[Li, Hao] Hospital of Shandong Aluminum Corporation, Department of Urology, 255069 Zibo, China.
[Men, Tong-Yi] Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, No.16766 Jingshi Road, 250014 Jinan, Shandong Province, China.
RP Men, TY (reprint author), Qianfoshan Hospital Affiliated to Shandong University, Department of Urology, 250014 Jinan, China.
EM mentongyish3316@sina.com
CR Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY, Sboner A, Esgueva R, Pflueger D, Sougnez C, 2011, The genomic complexity of primary human prostate cancer. Nature 470(7333):214–220
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Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL, 2011, Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25(18):1915–1927
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 43
EP 50
DI 10.1007/s12253-013-9618-0
PG 8
ER
PT J
AU Lu, C
Liu, G
Cui, X
Zhang, J
Wei, L
Wang, Y
Yang, X
Liu, Y
Cong, X
Lv, L
Ni, R
Huang, X
AF Lu, Cuihua
Liu, Guoliang
Cui, Xiaopeng
Zhang, Jing
Wei, Lixian
Wang, Yingying
Yang, Xiaojing
Liu, Yanhua
Cong, Xia
Lv, Liting
Ni, Runzhou
Huang, Xiaodong
TI Expression of SGTA Correlates with Prognosis and Tumor Cell Proliferation in Human Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Small glutamine-rich TPR-containing protein A (SGTA); Prognosis; Proliferation; Cell cycle
ID Hepatocellular carcinoma; Small glutamine-rich TPR-containing protein A (SGTA); Prognosis; Proliferation; Cell cycle
AB To investigate the potential role of small glutaminerich TPR-containing protein A (SGTA) in hepatocarcinogenesis, immunohistochemistry and Western blot were performed to detect the expression of SGTA in clinical Hepatocellular carcinoma (HCC) samples, adjacent nontumorous liver tissues and HCC cell lines. In addition, expression of SGTA was correlated with clinicopathological variables and univariate andmultivariate survival analyses were performed to determine the prognostic significance. Moreover, the biological significance of the aberrant expression of SGTA was investigated in vitro. Both immunohistochemistry evaluation and Western blot analyses demonstrated that SGTA was overexpressed in HCC tissues compared with adjacent nontumorous liver tissues. Expression of SGTA directly correlated with the histological grades of HCC and high expression of SGTA was associated with a poor prognosis. SGTA depletion by siRNA inhibited cell proliferation, blocked S-phase and mitotic entry in Huh7 cells. Western blot analyses showed that SGTA depletion decreased cyclin A and cyclin B levels. Taken together, owing to overexpression of SGTA in HCC and its important role in predicting poor prognosis and the development of HCC, SGTA could be a potential prognostic marker and therapeutic target of HCC.
C1 [Lu, Cuihua] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Liu, Guoliang] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Cui, Xiaopeng] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Zhang, Jing] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Wei, Lixian] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Wang, Yingying] Medical College of Nantong University, Department of Immunology and Microbiology, 226001 Nantong, Jiangsu, China.
[Yang, Xiaojing] Medical College of Nantong University, Department of Immunology and Microbiology, 226001 Nantong, Jiangsu, China.
[Liu, Yanhua] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Cong, Xia] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Lv, Liting] Medical College of Nantong University, Department of Immunology and Microbiology, 226001 Nantong, Jiangsu, China.
[Ni, Runzhou] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
[Huang, Xiaodong] Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, Jiangsu, China.
RP Ni, R (reprint author), Medical College of Nantong University, Affiliated Hospital of Nantong University, Department of Digestion, 226001 Nantong, China.
EM nirunzhou@sina.cn
CR Zhou P,Wu LL,Wu KM et al, 2012, Overexpression of MMSET is correlation with poor prognosis in hepatocellular carcinoma. Pathol Oncol Res 19(2):303–9
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 51
EP 60
DI 10.1007/s12253-013-9657-6
PG 10
ER
PT J
AU Doki, N
Ohashi, K
Oshikawa, G
Kobayashi, T
Kakihana, K
Sakamaki, H
AF Doki, Noriko
Ohashi, Kazuteru
Oshikawa, Gaku
Kobayashi, Takeshi
Kakihana, Kazuhiko
Sakamaki, Hisashi
TI Clinical Outcome of Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph + ALL): Experience From a Single Institution
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph + ALL); Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Tyrosine kinase inhibitor (TKI); Complete remission (CR)
ID Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph + ALL); Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Tyrosine kinase inhibitor (TKI); Complete remission (CR)
AB To identify factors affecting transplant outcome, data from 65 Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients who had undergone allogeneic hematopoietic transplantation (allo-HSCT) in our institution were analyzed. The probability of OS (overall survival) and DFS (disease free-survival) at 3 years after allo- HSCT was 40.1 % and 38 %, respectively. Multivariate analysis showed that gender and disease status (p=0.0059, p=0.0039, respectively) were significant factors for OS. Among 51 patients with CR (complete remission), multivariate analysis showed that the factors associated with OS included gender (p=0.014), number of white blood cell at diagnosis (p=0.025), and the source of stem cells (bone marrow versus. cord blood; BM stem cell source was associated with favorable OS, p=0.042). Twenty-one patients relapsed after allo-HSCT with a median of 207 days (range, 19–1,324 days). The estimated cumulative incidence of relapse at 3 years was 39.4%. Patients with CR showed a lower relapse rate at 3 years (34.2 %) when compared with patients with non-CR (62.7 %). Among 21 patients, eight patients received imatinib-based chemotherapy and 13 received chemotherapy without imatinib before HSCT. In terms of treatment after relapse, seven patients received chemotherapy with imatinib and 13 received chemotherapy without imatinib. Five patients underwent a second HSCT. One patient survived, and 20 patients died. In this study, disease status at time of allo-HSCT had a significant impact on OS, DFS, and relapse. Imatinib administration given before allo-HSCT was not associated with favorable outcome. Second-generation tyrosine kinase inhibitors may be more suitable candidates for Ph + ALL before and after allo-HSCT.
C1 [Doki, Noriko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Oshikawa, Gaku] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashi, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Doki, N (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM n-doki@cick.jp
CR Gleissner B, Gokbuget N, Bartram CR et al, 2002, Leading prognostic relevance of the BCR-ABLtranslocation in adult acute Blineage lymphoblastic leukemia: a prospective study of the German Multicenter Traial Group and confirmed polymerase chain reaction analysis. Blood 99:1536–1543
Vinetti M, Fazi P, Cimino G et al, 2007, Imatinib plus steroids induces complete remissons and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy:results of the Gruppo Italiano Malattie Ematologiche dell’Adulto, GI-MEMA, LAL0201-B protocol. Blood 109:3676–3678
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Caocci G, Vacca A, Ledda A et al, 2012, Prophylactic and preemptive therapy with dasatinib after hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Biol Blood Marrow Transplant 18:652–654
Teng CL, Yu JT, Chen HC, Hwang WL, 2013, Maintenance therapy with dasatinib after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Hematol., DOI 10.1007/s00277−012-1670-4
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 61
EP 66
DI 10.1007/s12253-013-9658-5
PG 6
ER
PT J
AU Wozniak, K
Krupa, R
Synowiec, E
Morawiec, Z
AF Wozniak, Katarzyna
Krupa, Renata
Synowiec, Ewelina
Morawiec, Zbigniew
TI Polymorphism of UBC9 Gene Encoding the SUMO-E2- Conjugating Enzyme and Breast Cancer Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE UBC9 gene and protein; Breast cancer; Sumoylation
ID UBC9 gene and protein; Breast cancer; Sumoylation
AB UBC9 protein (E2-conjugating enzyme) plays a key role in post-translation modification named sumoylation. Proteins, which are sumoylated take part in many cellular processes including cell growth, maintaining the genome integrity and stability and cancer development. The aim of this study was to investigate an association between three polymorphisms of the UBC9 gene: c.73G>A (rs11553473), c.430T>G (rs75020906) and g.1289209T>C (rs7187167) and a risk of ductal breast cancer occurrence. We performed a case-control study in 181 breast cancer cases and 277 controls using PCR-RLFP and ASO-PCR. In the case of the 430T>G polymorphism of the UBC9 gene lack of variability suggests that there is not a polymorphic site in polish population. We observed that a risk of breast cancer occurrence is elevated in patients with the G/A genotype (OR 5.03; 95 % Cl 3.05–8.28), the A/A genotype (OR 11.3; 95 % Cl 4.24–30.3) and the A allele (OR 6.86; 95 % Cl 4.43–10.6) of the c.73G>A polymorphism. In the case of the g.1289209T>C polymorphism we found a correlation between estrogen receptor (ER) expression and the T/T genotype (OR 0.22; 95 % Cl 0.07–0.64) and the T allele (OR 0.53; 95 % Cl 0.32–0.88). We also found a correlation between the T/T genotype (OR 4.13; 95 % Cl 1.21–14.1) and the T allele (OR 2.09; 95 % Cl 1.07–4.08) of the g.1289209T>C polymorphism with triple negative breast cancer. Our results suggest that the variability of the UBC9 gene can play a role in breast cancer occurrence.
C1 [Wozniak, Katarzyna] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Krupa, Renata] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Synowiec, Ewelina] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Morawiec, Zbigniew] N. Copernicus Hospital, Department of Surgical OncologyLodz, Poland.
RP Wozniak, K (reprint author), University of Lodz, Department of Molecular Genetics, Lodz, Poland.
EM wozniak@biol.uni.lodz.pl
CR Seeler J-S, Bischof O, Nacerddine K, Dejean A, 2007, SUMO, the three rs and cancer. CTMI 313:49–71
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Zhu S, Sachdeva M, Wu F, Lu Z, Mo YY, 2010, Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner. Oncogene 29:1763–1772
Ronen O, Malone JP, Kay P, Bivens C, Hall K, Paruchuri LP,Mo YY, Robbins KT, Ran S, 2009, Expression of a novel marker, Ubc9, in squamous cell carcinoma of the head and neck. Head Neck 31:845–855
Driscoll JJ, Pelluru D, Lefkimmiatis K, Fulciniti M, Prabhala RH, Greipp PR, Barlogie B, Tai YT, Anderson KC, Shaughnessy JD Jr, Annunziata CM, Munshi NC, 2010, The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome. Blood 115:2827–2834
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Dunnebier T, Bermejo JL, Haas S, Fischer HP, Pierl CB, Justenhoven C, Brauch H, Baisch C, Gilbert M, Harth V, Spickenheuer A, Rabstein S, Pesch B, Bruning T, Ko YD, Hamann U, 2009, Common variants in the UBC9 gene encoding the SUMO-conjugating enzyme are associated with breast tumor grade. Int J Cancer 125:596–602
Dunnebier T, Bermejo JL, Haas S, Fischer HP, Pierl CB, Justenhoven C, Brauch H, Baisch C, Gilbert M, Harth V, Spickenheuer A, Rabstein S, Pesch B, Bruning T, Ko YD, Hamann U, 2010, Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and breast cancer risk. Breast Cancer Res Treat 121:185–194
Synowiec E, Krupa R, Morawiec Z,WasyleckaM, Dziki L, Morawiec J, Blasiak J,Wozniak K, 2010, Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism. Mutat Res 694:31–38
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 67
EP 72
DI 10.1007/s12253-013-9659-4
PG 6
ER
PT J
AU Zhou, F
Xu, J
Ding, G
Cao, L
AF Zhou, Fan
Xu, Jiewei
Ding, Guoping
Cao, Liping
TI Overexpressions of CK2β and XIAP are Associated with Poor Prognosis of Patients with Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Protein kinase CK2; Casein kinase 2; X-Linked inhibitor of apoptosis protein; Cholangiocarcinoma; Prognosis
ID Protein kinase CK2; Casein kinase 2; X-Linked inhibitor of apoptosis protein; Cholangiocarcinoma; Prognosis
AB To investigate the expressions of casein kinase II β(CK2β) and X-Linked inhibitor of apoptosis protein (XIAP) in cholangiocarcinoma (CCA) and evaluated their correlations with major clinicopathologic features and patients’ survival. Fifty CCA specimens and 20 normal liver tissues were included in the study. Immunohistochemical staining was used to determine the expression levels of CK2β, XIAP in normal and CCA tissues. The relationships of CK2β and XIAP expressions with clinicopathologic parameters and clinical outcome were evaluated. High immunostaining of CK2β and XIAP were observed in 66 % (33/50) and 68 % (34/50) of CCA tissues, which were significantly higher than that of normal liver tissues 0 % (0/20) and 25 % (5/20). The high expression of CK2β was significantly associated with TNM stage (P=0.036), histological grade (P=0.020) and high serum CEA level(P=0.010), while high expression of XIAP was only associated with TNM stage(P=0.014) and high serum CEA level(P=0.001). By univariant analysis, patients with high expression of CK2β and XIAP demonstrate significantly poorer overall survival (P=0.003 vs P=0.018). Cox regression model showed that positive expression of CK2βis an independent factor of prognosis (P=0.004). The expressions of CK2β and XIAP in CCA tissues showed strong correlations with the tumor progression, CK2β may be applied as a potential prognostic marker for CCA.
C1 [Zhou, Fan] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Xu, Jiewei] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Ding, Guoping] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Cao, Liping] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
RP Cao, L (reprint author), School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
EM cao@zju.edu.cn
CR Blechacz B, Gores GJ, 2008, Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology 48:308–321., DOI 10.1002/hep.22310
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Shaib YH, Davila JA, McGlynn K et al, 2004, Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol 40:472–477., DOI 10.1016/j.jhep.2003.11.030
Patel T, 2001, Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33:1353–1357., DOI 10.1053/jhep. 2001.25087
Zhang P, Davis AT, Ahmed K, 1998, Mechanism of protein kinase CK2 association with nuclear matrix: role of disulfide bond formation. J Cell Biochem 69:211–220
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 73
EP 79
DI 10.1007/s12253-013-9660-y
PG 7
ER
PT J
AU Yongxiang, W
Liang, G
Qinshu, Sh
AF Yongxiang, Wang
Liang, Gao
Qinshu, Shao
TI Apoptosis of Human Pancreatic Carcinoma PC-2 Cells by an Antisense Oligonucleotide Specific to Point Mutated K-ras
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic carcinoma; K-ras gene; Antisense oligonucleotide; Target gene
ID Pancreatic carcinoma; K-ras gene; Antisense oligonucleotide; Target gene
AB The prognosis of pancreatic carcinoma is poor due to the difficulty in early diagnosis, insensitivity to routine therapies and limited understanding of its pathological mechanisms. Gene therapy is now becoming an important strategy for the treatment of pancreatic carcinoma, which includes antisense gene therapy. In this study, we investigated the effect of an antisense oligonucleotide specific to point mutated K-ras on the apoptosis of human pancreatic carcinoma cells in vitro. Human pancreatic carcinoma PC-2 cells were transfected with an antisense oligonucleotide specific to a K-ras point mutation by liposomes. The effect of the antisense oligonucleotide on the apoptosis of PC-2 cells was studied using flow cytometry, TUNEL, and phase contrast microscopy. An apoptotic peak was observed in the experimental group, and most cells were arrested at the G1 phase with few cells at the S phase. The numbers of apoptotic cells in the experimental group increased as indicated by TUNEL and phase contrast microscopy. An antisense oligonucleotide specific to a K-ras point mutation promotes apoptosis in PC-2 cells in vitro perhaps by inhibition of ras gene expression.
C1 [Yongxiang, Wang] Zhejiang Provincial People’s Hospital, Department of General Surgery, 310014 Hangzhou, China.
[Liang, Gao] Zhejiang Provincial People’s Hospital, Department of Oncology, 310014 Hangzhou, China.
[Qinshu, Shao] Zhejiang Provincial People’s Hospital, Department of General Surgery, 310014 Hangzhou, China.
RP Liang, G (reprint author), Zhejiang Provincial People’s Hospital, Department of Oncology, 310014 Hangzhou, China.
EM yxwang910@yahoo.com.cn
CR Zongzheng J, Yongxiang W, Xi C, Tao W, 2003, Peripancreatic artery ligation and artery infusion chemotherapy for advanced pancreatic carcinoma. Chin Med J 116:89–92
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Shuanzeng W, Tonghua L, Hongrui L, Jie G, 2003, Unique GGT→GTT mutation at K-ras codon 12 in six human pancreatic cancer cell lines from Chinese patients. Chin Med J 116:1585–1587
Luttges J, Stigge C, Pacena M, Kloppel G, 2004, Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years. Cancer 100:173–182
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Matsubayashi H, Watanabe H, Ajioka Y, Nishikura K, Yamano M, Seki T et al, 2000, Different amounts of K-ras mutant epithelial cells in pancreatic carcinoma and mass-forming pancreatitis. Pancreas 21:77–85
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 81
EP 85
DI 10.1007/s12253-013-9661-x
PG 5
ER
PT J
AU Igci, ZY
Erkilic, S
Igci, M
Arslan, A
AF Igci, Ziya Yusuf
Erkilic, Suna
Igci, Mehri
Arslan, Ahmet
TI MCM3 Protein Expression in Follicular and Classical Variants of Papillary Thyroid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid carcinoma; Follicular variant of papillary thyroid carcinoma; Classic variant of papillary thyroid carcinoma; MCM; MCM3
ID Papillary thyroid carcinoma; Follicular variant of papillary thyroid carcinoma; Classic variant of papillary thyroid carcinoma; MCM; MCM3
AB Minichromosome maintenance (MCM) proteins are needed as licensors in the DNA replication of eukaryotic cells and transcriptional control of MCM genes has critical role in the regulation of MCM functions. Different MCM protein family members are proposed as diagnostic or prognostic markers in various cancers due to their increased proliferative potential. Among MCM family members, minichromosome maintenance protein 3 (MCM3) expressions in both mRNA and protein levels were shown to be associated with papillary thyroid carcinoma (PTC). But, the usability of MCM3 in some histological variants of PTC might be controversial due to tissue specific molecular heterogeneities. In follicular variant of papillary thyroid carcinoma (FVPTC), a number of genes including MCM3 were shown to be differentially expressed which were specific to this kind of variant. Using immunohistochemistry method, MCM3 protein expression levels were compared in FVPTC, classic variant of papillary thyroid carcinoma (CVPTC), and multi-nodular goiter (MNG) tissues in a group of 32 cases. There was meaningful differences between MNG vs. FVPTC (p=0.016) and MNG vs. CVPTC (p=0.019) while there was no significant difference in the comparison FVPTC vs. CVPTC (p=0.15). Four of the 5 CVPTC cases having surrounding tissue invasion had high expression values. For FVPTC and CVPTC, MCM3 protein expression results were parallel to our previous mRNA expression study while there was downregulation in protein expression despite the increased expression of MCM3 mRNA in MNG suggesting tissue-specific post-transcriptional events in benign thyroid neoplasms of which should be focused on. Moreover, the relatively lower MCM3 protein expression in FVPTC comparing to CVPTC could be due to a different tumorigenic pathway favored in this type of tissue.
C1 [Igci, Ziya Yusuf] University of Gaziantep, Faculty of Medicine, Department of Medical Biology, 27310 Gaziantep, Turkey.
[Erkilic, Suna] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Igci, Mehri] University of Gaziantep, Faculty of Medicine, Department of Medical Biology, 27310 Gaziantep, Turkey.
[Arslan, Ahmet] University of Gaziantep, Faculty of Medicine, Department of Medical Biology, 27310 Gaziantep, Turkey.
RP Igci, ZY (reprint author), University of Gaziantep, Faculty of Medicine, Department of Medical Biology, 27310 Gaziantep, Turkey.
EM igci@gantep.edu.tr
CR Jemal A, Siegel R, Xu J,Ward E, 2010, Cancer statistics, 2010. CA Cancer J Clin 60:277–300
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Ertek S, Yilmaz NC, Cicero AF, Vurupalmaz O, Demiroz AS, Erdogan G, 2012, Increasing diagnosis of thyroid papillary carcinoma follicular variant in south-east Anatolian region: comparison of characteristics of classical papillary and follicular variant thyroid cancers. Endocr Pathol 23:157–160
Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, Tuttle RM, Ghossein RA, 2006, Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer 107:1255–1264
LiVolsi VA, 2011, Papillary thyroid carcinoma: an update. Mod Pathol 24(Suppl 2):S1–S9
Salajegheh A, Petcu EB, Smith RA, Lam AK, 2008, Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists. Postgrad Med J 84:78–82
Igci YZ, Arslan A, Akarsu E, Erkilic S, Igci M, Oztuzcu S, Cengiz B, Gogebakan B, Cakmak EA, Demiryurek AT, 2011, Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma. Endocr Pathol 22:86–96
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Melck A, Masoudi H, Griffith OL, Rajput A, Wilkins G, Bugis S, Jones SJ,Wiseman SM, 2007, Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer. Ann Surg Oncol 14:3403–3411
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Zhu M,Wang F, Yan F, Yao PY, Du J, Gao X,Wang X,Wu Q,Ward T, Li J, Kioko S, Hu R, Xie W, Ding X, Yao X, 2008, Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization. J Biol Chem 283:18916–18925
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 87
EP 91
DI 10.1007/s12253-013-9662-9
PG 5
ER
PT J
AU Chang, L
Guo, F
Wang, Y
Lv, Y
Huo, B
Wang, L
Liu, W
AF Chang, Liang
Guo, Fengjie
Wang, Yudong
Lv, Yalei
Huo, Bingjie
Wang, Long
Liu, Wei
TI MicroRNA-200c Regulates the Sensitivity of Chemotherapy of Gastric Cancer SGC7901/DDP Cells by Directly Targeting RhoE
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA-200c; Gastric cancer; RhoE; Drug resistance
ID MicroRNA-200c; Gastric cancer; RhoE; Drug resistance
AB Gastric cancer remains a worldwide burden as the second leading cause of cancer-related death. Drug resistance of chemotherapy looms as a major clinical obstacle to successful treatment. Recent evidence indicated that miRNA-200c can restore the sensitivity of NSCLC cells to cisplatin and cetuximab. The expression of miRNA-200c and RhoE were investigated in gastric cancer tissues and cells (SGC7901 and SGC7901/DDP) by qRT-PCR. A luciferase reporter assay was done to understand the potential correlation between miRNA-200c and RhoE. Pre-miR-200c was transfected in SGC7901/DDP cells to confirm whether miRNA-200c could regulate RhoE expression. RhoE was knocked down to explore the role of RhoE on sensitivity of chemotherapy in gastric cancer by MTT. Western blot analysis was performed to further explore the mechanism of RhoE in regulating drug resistance. The results showed that miRNA-200c was significantly lower in cancerous tissues than those in the paired normal tissues, whereas the expression of RhoE was just the opposite. The significant difference of miRNA-200c and RhoE were observed between SGC7901 cells and SGC7901/DDP cells. miRNA-200c has target sites in the 3’-UTR of RhoE mRNA by luciferase reporter assay. Transfection of pre-miR-200c reduces RhoE expression. Meanwhile, the knockdown of RhoE enhanced the sensitivity of SGC7901/DDP cells and changed expression of some genes. These suggested that miRNA-200c regulated the sensitivity of chemotherapy to cisplatin (DDP) in gastric cancer by possibly targeting RhoE.
C1 [Chang, Liang] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
[Guo, Fengjie] Tianjin Medical University General Hospital, Tianjin Lung Cancer InstituteTianjin, China.
[Wang, Yudong] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
[Lv, Yalei] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
[Huo, Bingjie] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
[Wang, Long] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
[Liu, Wei] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 12 Jiankang RoadShijiazhuang, Hebei Province, China.
RP Liu, W (reprint author), Fourth Hospital of Hebei Medical University, Department of Medical Oncology, Shijiazhuang, China.
EM changliang1081@163.com
CR Lee JH, Kim KM, Cheong JH, Noh SH, 2012, Current management and future strategies of gastric cancer. Yonsei Med J 53(2):248–257
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Schoof CR, Botelho EL, Izzotti A, Vasques Ldos R, 2012, MicroRNAs in cancer treatment and prognosis. Am J Cancer Res 2(4):414–433
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Davalos V, Moutinho C, Villanueva A, Boque R, Silva P, Carneiro F, Esteller M, 2012, Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene 31(16):2062–2074
Roybal JD, Zang Y, Ahn YH, Yang Y, Gibbons DL, Baird BN, Alvarez C, Thilaganathan N, Liu DD, Saintigny P, Heymach JV, Creighton CJ, Kurie JM, 2011, miR-200 inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1. Mol Cancer Res 9(1):25–35
Yu J, Ohuchida K, Mizumoto K, Sato N, Kayashima T, Fujita H, Nakata K, Tanaka M, 2010, MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation. Mol Cancer 9:169
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Madigan JP, Bodemann BO, Brady DC, Dewar BJ, Keller PJ, Leitges M, Philips MR, Ridley AJ, Der CJ, Cox AD, 2009, Regulation of Rnd3 localization and function by protein kinase C alpha-mediated phosphorylation. Biochem J 424(1):153–161
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Jurmeister S, Baumann M, Balwierz A, Keklikoglou I, Ward A, Uhlmann S, Zhang JD, Wiemann S, Sahin O, 2012, MicroRNA- 200c represses migration and invasion of breast cancer cells by targeting actin-regulatory proteins FHOD1 and PPM1F. Mol Cell Biol 32(3):633–651
Lo WL, Yu CC, Chiou GY, Chen YW, Huang PI, Chien CS, Tseng LM, Chu PY, Lu KH, Chang KW, Kao SY, Chiou SH, 2011, MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells. J Pathol 223(4):482–495
Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK, 2009, MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther 8(5):1055–1066
Leskela S, Leandro-Garcia LJ, Mendiola M, Barriuso J, Inglada- Perez L, Munoz I, Martinez-Delgado B, Redondo A, de Santiago J, Robledo M, Hardisson D, Rodriguez-Antona C, 2010, The miR- 200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. Endocr Relat Cancer 18(1):85–95
Collett GP, Goh XF, Linton EA, Redman CW, Sargent IL, 2012, RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells. PLoS One 7(1):e30453
Poch E, Minambres R, Mocholi E, Ivorra C, Perez-Arago A, Guerri C, Perez-Roger I, Guasch RM, 2007, RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line. Exp Cell Res 313(4):719–731
Cuiyan Z, Jie H, Fang Z, Kezhi Z, Junting W, Susheng S, Xiaoli F, Ning L, Xinhua M, Zhaoli C, Kang S, Bin Q, Baozhong L, Sheng C, Meihua X, Jie H, 2007, Overexpression of RhoE in Non-small Cell Lung Cancer, NSCLC, is associated with smoking and correlates with DNA copy number changes. Cancer Biol Ther 6(3):335–342
Klein RM, Higgins PJ, 2011, A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition. Mol Cancer 10:114
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 93
EP 98
DI 10.1007/s12253-013-9664-7
PG 6
ER
PT J
AU Nelhubel, AGy
Karoly, B
Szabo, B
Lotz, G
Kiss, A
Tovari, J
Kenessey, I
AF Nelhubel, A Gyorgyi
Karoly, Boroka
Szabo, Balazs
Lotz, Gabor
Kiss, Andras
Tovari, Jozsef
Kenessey, Istvan
TI The Prognostic Role of Claudins in Head and Neck Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Claudin; Head and neck squamous cell carcinoma; Prognosis; Immunohistochemistry; Tight junction
ID Claudin; Head and neck squamous cell carcinoma; Prognosis; Immunohistochemistry; Tight junction
AB The expression of tight junction proteins is frequently altered in epithelial cancers. The loss of cell-cell adhesion associates with enhanced metastatic potential, which underlies the role of altered expression pattern of tight junction component claudins (CLDNs). Our study assessed the expression of CLDN 1, 2, 3, 4, 7, 8 and 10 in squamous cell carcinoma of the head and neck region (HNSCC) including oropahrynx, larynx, and hypopharynx in comparison to normal epithelial tissue of the same patient. The surgical samples were examined by tissue microarray and immunohistochemistry, the expression was calculated by H-score, which took account of intensity and percentage of positivity as well. Both normal and cancerous tissue proved negative for CLDN 3, 8 and 10. Normal epithelia showed mild expression of CLDN 4, but the minimal positivity disappeared in squamous cancer. In case of CLDN 1 and CLDN 7 we demonstrated significantly increased intensity in cancer, while CLDN 2 showed decreased expression compared with normal epithelium. The normal polarity and distribution of claudins were lost in HNSCC. Moreover, preserved expression of CLDN 2 (but not that of 1 and 7) was associated with better survival, which suggested a potential prognostic role of CLDN 2.
C1 [Nelhubel, A Gyorgyi] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Karoly, Boroka] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Szabo, Balazs] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Tovari, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Kenessey, I (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM steveken12@yahoo.com
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Nichols LS, Ashfaq R, Iacobuzio-Donahue CA, 2004, Claudin 4 protein expression in primary and metastatic pancreatic cancer: Support for use as a therapeutic target. Am J Clin Pathol 121:226–230
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 99
EP 106
DI 10.1007/s12253-013-9665-6
PG 8
ER
PT J
AU Krawczyk, P
Nicos, M
Ramlau, R
Powrozek, T
Wojas-Krawczyk, K
Sura, S
Jarosz, B
Szumilo, J
Warda, E
Mazurkiewicz, T
Sawicki, M
Milanowski, J
AF Krawczyk, Pawel
Nicos, Marcin
Ramlau, Rodryg
Powrozek, Tomasz
Wojas-Krawczyk, Kamila
Sura, Sylwia
Jarosz, Bozena
Szumilo, Justyna
Warda, Edward
Mazurkiewicz, Tomasz
Sawicki, Marek
Milanowski, Janusz
TI The Incidence of EGFR-Activating Mutations in Bone Metastases of Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; EGFR gene mutations; Bone metastases; EGFR tyrosine kinase inhibitors
ID Lung adenocarcinoma; EGFR gene mutations; Bone metastases; EGFR tyrosine kinase inhibitors
AB Poor prognosis of lung adenocarcinoma is associated with early occurrence of distant metastases. This type of non-small-cell lung carcinoma more frequently involves EGFR gene abnormalities, which determine the efficacy of EGFR tyrosine kinase inhibitor therapies (EGFR TKIs). It is probable that genetic abnormalities present in primary tumor will also be present in metastases. Unfortunately little is known about the incidence of these mutations in the metastases and about the effectiveness ofmolecularly targeted therapy in such patients. Formalin-fixed, paraffin-embedded tumor tissue was prepared from 431 samples of primary adenocarcinoma, 61 of adenocarcinoma central nervous system (CNS) metastases and 8 of adenocarcinoma bone metastases. The presence of exon 19 deletions was examined using the PCR technique and amplified PCR product fragment length analysis. The ASP-PCR technique was used to evaluate the L858R substitutions in exon 21, and the results were analyzed using ALF Express II sequencer. In the adenocarcinoma metastases to bone obtained from 8 patients, deletions in exon 19 of the EGFR gene were revealed in 3 smoking men and one nonsmoking woman, while L858R substitution in exon 21 was found in one smoking woman and one man of unknown smoking status. The incidence of EGFR gene mutations in the bonemetastases was 75 %, in the primary adenocarcinoma - 12.8 %, and in the adenocarcinoma metastases to CNS - 14.75 %. Five patients with EGFR gene mutation revealed in bone metastases were treated with EGFR TKIs; the majority of them had a satisfactory response to therapy.
C1 [Krawczyk, Pawel] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Nicos, Marcin] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Ramlau, Rodryg] Greater Poland Center of Pulmonology and Thoracic Surgery of Eugenia and Janusz ZeylandPoznan, Poland.
[Powrozek, Tomasz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Wojas-Krawczyk, Kamila] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Sura, Sylwia] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Jarosz, Bozena] Medical University of Lublin, Neurosurgery and Pediatric Neurosurgery DepartmentLublin, Poland.
[Szumilo, Justyna] Medical University of Lublin, Department of Clinical PathomorphologyLublin, Poland.
[Warda, Edward] Medical University of Lublin, Orthopedics and Traumatology DepartmentLublin, Poland.
[Mazurkiewicz, Tomasz] Medical University of Lublin, Orthopedics and Traumatology DepartmentLublin, Poland.
[Sawicki, Marek] Medical University of Lublin, Thoracic Surgery DepartmentLublin, Poland.
[Milanowski, Janusz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
RP Krawczyk, P (reprint author), Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, 20-954 Lublin, Poland.
EM krapa@poczta.onet.pl
CR Jemal A, Bray F, Center MM et al, 2011, Global cancer statistic. CA Cancer J Clin 61:69–90
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 107
EP 112
DI 10.1007/s12253-013-9667-4
PG 6
ER
PT J
AU Naserpour Farivar, T
Johari, P
Najafipour, R
Farzam, A
Nasirian, N
HajManouchehri, F
Jahani Hashemi, H
Azimi, A
Bahrami, M
AF Naserpour Farivar, Taghi
Johari, Pouran
Najafipour, Reza
Farzam, Amir
Nasirian, Neda
HajManouchehri, Fatemeh
Jahani Hashemi, Hassan
Azimi, Akram
Bahrami, Mohammad
TI The Relationship Between Gastric Cancer and Helicobacter Pylori in Formaldehyde Fixed Paraffin Embedded Gastric Tissues of Gastric Cancer Patients-Scorpion Real-Time PCR Assay Findings
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Scorpion; Real-time; Helicobacter pylori; Gastric; Cancer
ID Scorpion; Real-time; Helicobacter pylori; Gastric; Cancer
AB Gastric cancer is the second leading cause of cancerrelated deaths worldwide and it seems that environmental and lifestyle factors and infection with Helicobacter pylori (H.pylori) have had a major role in the etiology of gastric cancer. The aim of this study was to investigate the presence of H. pylori DNA in archival gastric tissues of patients with gastric cancer disease by rapid, sensitive and specific technique of Scorpion Realtime PCR. This retrospective cross-sectional study was performed on 285 paraffin embedded gastric specimens of patients who were pathologically proved for gastric cancer admitted in Bou- Ali, Shahid Rajaie and Dehkhoda hospitals and Bahar and Farzam private laboratory in Qazvin city in Iran during 2009 and 150 paraffin embedded pathological specimens of patients with other proved diagnosis other than gastric cancer. Results of our Scorpion Realtime PCR analysis showed that DNA of H. pylori DNA was present in 78.42 % of our total specimens. Modified McMullen’s Staining of paraffin embedded sections was positive in 210 patients. Also we were not able to finding significant relationship between demographic characteristics of our studied patients and presence of H. pylori DNA in their formaldehyde fixed paraffin embedded gastric tissues samples. Existence of H. pylori in gastric tissue samples of patients with gastric cancer is controversial and our results indicated that in our studied specimens prevalence of H.pylori was significantlymore than recent published reports.
C1 [Naserpour Farivar, Taghi] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Johari, Pouran] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Najafipour, Reza] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Farzam, Amir] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Nasirian, Neda] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[HajManouchehri, Fatemeh] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Jahani Hashemi, Hassan] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Azimi, Akram] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
[Bahrami, Mohammad] Qazvin University of Medical Sciences, Cellular and Molecular Reasearch CenterQazvin, Iran.
RP Najafipour, R (reprint author), Qazvin University of Medical Sciences, Cellular and Molecular Reasearch Center, Qazvin, Iran.
EM rnajafipour@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 113
EP 117
DI 10.1007/s12253-013-9669-2
PG 5
ER
PT J
AU Lokamani, I
Looi, ML
Md Ali, AS
Mohd Dali, ZHA
Ahmad Annuar, AM
Jamal, R
AF Lokamani, Ilambarthi
Looi, Mee-Lee
Md Ali, Aishah Siti
Mohd Dali, Zailani Hatta Ahmad
Ahmad Annuar, Azrif Muhammad
Jamal, Rahman
TI Gelsolin and Ceruloplasmin as Potential Predictive Biomarkers for Cervical Cancer by 2D-DIGE Proteomics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 2D-DIGE; Cervical neoplasia; Gelsolin; ceruloplasmin; proteomics
ID 2D-DIGE; Cervical neoplasia; Gelsolin; ceruloplasmin; proteomics
AB This study aimed to identify candidate proteins which may serve as potential biological markers for cervical cancer using 2D-DIGE. Serum samples of controls, patients with cervical intraepithelial neoplasia grade 3 (CIN 3), squamous cell carcinoma of early (SCC I and II) and late (SCC III and IV) stage were subjected to 2D-DIGE. Differentially expressed spots were identified by tandem mass spectrometry. Validation of candidate proteins in serum and tissue samples were then performed by ELISA and immunohistochemistry (IHC) analysis respectively. A total of 20 differentially expressed proteins were identified. These proteins were found to play key roles in the apoptosis pathway, complement system, various types of transportation such as hormones, fatty acids, lipid, vitamin E and drug transportation, coagulation cascade, regulation of iron and immunologic response. Based on their functional relevancy to the progression of various cancers, 4 proteins namely the complement factor H, CD5- like antigen, gelsolin and ceruloplasmin were chosen for further validation using ELISA. Biological network analysis showed that ceruloplasmin and gelsolin are closely interacted with the oncogene NF-κb. These two proteins were further validated using the IHC. Gelsolin and ceruloplasmin may serve as potential predictive biomarkers for the progression of high grade lesions.
C1 [Lokamani, Ilambarthi] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Level 7, Clinical Block, UKM Medical Centre, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
[Looi, Mee-Lee] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Level 7, Clinical Block, UKM Medical Centre, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
[Md Ali, Aishah Siti] Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Pathology, 56000 Kuala Lumpur, Malaysia.
[Mohd Dali, Zailani Hatta Ahmad] Universiti Kebangsaan Malaysia, Obstetrics and Gynecology Department, 56000 Kuala Lumpur, Malaysia.
[Ahmad Annuar, Azrif Muhammad] Universiti Kebangsaan Malaysia, Faculty of Medicine, Radiology Department, 56000 Kuala Lumpur, Malaysia.
[Jamal, Rahman] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Level 7, Clinical Block, UKM Medical Centre, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
RP Jamal, R (reprint author), Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), 56000 Kuala Lumpur, Malaysia.
EM rahmanj@ppukm.ukm.edu.my
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 119
EP 129
DI 10.1007/s12253-013-9670-9
PG 11
ER
PT J
AU Vosmik, M
Laco, J
Sirak, I
Beranek, M
Hovorkova, E
Vosmikova, H
Drastikova, M
Hodek, M
Zoul, Z
Odrazka, K
Petera, J
AF Vosmik, Milan
Laco, Jan
Sirak, Igor
Beranek, Martin
Hovorkova, Eva
Vosmikova, Hana
Drastikova, Monika
Hodek, Miroslav
Zoul, Zdenek
Odrazka, Karel
Petera, Jiri
TI Prognostic Significance of Human Papillomavirus (HPV) Status and Expression of Selected Markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki67/MIB-1) on Outcome After (Chemo-) Radiotherapy in Patients with Squamous Cell Carcinoma of Uterine Cervix
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine cervix; Immunohistochemistry; Squamous cell carcinoma; Prognostic factors; Human papillomavirus
ID Uterine cervix; Immunohistochemistry; Squamous cell carcinoma; Prognostic factors; Human papillomavirus
AB The aim of the retrospective study was to evaluate prognostic significance of human papillomavirus (HPV) status and expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2/neu), vascular endothelial growth factor (VEGF), CD34 antigen, tumor suppressors p63 and p53, and Ki67/ MIB-1 in squamous cell carcinoma of the uterine cervix (SCCC) treated with radiotherapy or chemoradiotherapy. Seventy-two consecutive patients with SCCC, diagnosed and treated with (chemo-) radiotherapy with a curative intent at the University Hospital Hradec Kralove between August 1998 and August 2008, were enrolled in the study. The median follow-up period was 57 months (range 5–152). The tested biological factors were evaluated by polymerase chain reaction (HPV status) and by immunohistochemistry (remaining above mentioned markers) from archival paraffin embedded original diagnostic tumor samples. A statistical significant correlation was observed between low expression of p63 and poor overall survival (p =0.001), although the complete response probability was influenced with borderline statistical significance (p=0.05). However, the results could be affected by the statistical error due to the small number of p63 negative patients. HPV positivity and EGFR staining intensity was associated with higher complete response probability (p =0.038 and p =0.044, resp.). All other results were not significant. Neither HPV positivity nor EGFR staining intensity were reflected in the overall survival evaluation. In conclusion, the presented study did not confirm any apparently significant association of the suggested markers with prognosis of SCCC in patients treated with (chemo-) radiotherapy.
C1 [Vosmik, Milan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Laco, Jan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Sirak, Igor] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Beranek, Martin] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Hovorkova, Eva] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Vosmikova, Hana] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Drastikova, Monika] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Hodek, Miroslav] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Zoul, Zdenek] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Odrazka, Karel] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
[Petera, Jiri] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec KraloveHradec Kralove, Czech Republic.
RP Vosmik, M (reprint author), Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, 500 05 Hradec Kralove, Czech Republic.
EM milan.vosmik@fnhk.cz
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Gaffney DK, Haslam D, Tsodikov A, Hammond E, Seaman J, Holden J, Lee RJ, Zempolich K, Dodson M, 2003, Epidermal growth factor receptor, EGFR, and vascular endothelial growth factor, VEGF, negatively affect overall survival in carcinoma of the cervix treated with radiotherapy. Int J Radiat Oncol Biol Phys 56:922–928
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Sobin LH, Wittekind C, 2002, UICC international union against cancer TNM classification of malignant tumours, 6th edn. Wiley- Liss, New York
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 131
EP 137
DI 10.1007/s12253-013-9674-5
PG 7
ER
PT J
AU Bardi, E
Csoka, M
Garai, I
Szegedi, I
Muller, J
Gyorke, T
Kajary, K
Nemes, K
Kiss, Cs
Kovacs, G
AF Bardi, Edit
Csoka, Monika
Garai, Ildiko
Szegedi, Istvan
Muller, Judit
Gyorke, Tamas
Kajary, Kornelia
Nemes, Karolina
Kiss, Csongor
Kovacs, Gabor
TI Value of FDG-PET/CT Examinations in Different Cancers of Children, Focusing on Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Childhood cancers; FDG-PET/CT; Hodgkin; Non-Hodgkin lymphoma; High grade solid tumors
ID Childhood cancers; FDG-PET/CT; Hodgkin; Non-Hodgkin lymphoma; High grade solid tumors
AB The aim of the study was to assess sensitivity and specificity of FDG-PET/CT in different forms of childhood cancer. We retrospectively evaluated the results dedicated of 162 FDG-PET/CT examinations of 86 children treated with: Hodgkin lymphoma (HL; n=31), non-Hodgkin lymphoma (NHL; n=30) and other high grade solid tumors (n=25). Patients were admitted and treated in two departments of pediatric hematology and oncology in Hungary. FDG-PET/CT was performed for staging (n=25) and for posttreatment evaluation (n=137). Imaging was performed in three FDG-PET/CT Laboratories, using dedicated PET/CT scanners. False positive results were defined as resolution or absence of disease progression over at least 1 year on FDG-PET/CT-scans without any intervention. In some cases histopathological evaluation of suspicious lesions was performed. Fals negative results were defined as negative FDG-PET/CT results in case of active malignancy. Positive predictive values (PPV) and negative predictive values (NPV) were calculated. NPV was 100 %. The highest PPV was observed in high grade solid tumors (81 %), followed by HL (65 %) and NHL (61 %). There was a major difference of PPV in different histological types of HL (50 % in HL of mixed-cellularity subtype, 90 % in nodular sclerosing, and 100 % in lymphocyte-rich and lymphocyte depleted HL). We treated one patient with nodular lymphocyte predominant HL, who had 5 false positive FDG-PET/CT results. PPV of Tand B-lineage NHL were similar (60%and 62 %, respectively). We observed an interesting difference of PPV in different stages of HL and NHL. In HL PPV was higher in early than in advanced disease forms: 66 % in stage II HL and 60 % in stage III HL, whereas there was an inverse relationship between PPV and disease stages in NHL 0%in stage I and II patients, 67%in stage III and 100 % in stage IV patients. PPV was lower in males (54 %) than in females (65 %). PPV were 64 % vs. 58 % in patients under vs. over 10 years of age. Negative FDG-PET/ CT results during follow-up reliably predict the absence of malignancy. Positive FDG-PET/CT scan results in general have a low PPV. The relatively high PPV in patients with histologically proven high grade solid tumors, advanced stages of NHL and with nodular sclerosing, lymphocyte-rich and lymphocyte depleted subtypes of HL warrant a confirmation by biopsy, whereas the watch-and-wait approach can be used in other forms of childhood cancer patients with a positive FDG-PET/ CT result in course of follow-up examinations.
C1 [Bardi, Edit] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Garai, Ildiko] Scanomed Kft.Debrecen, Hungary.
[Szegedi, Istvan] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Muller, Judit] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Gyorke, Tamas] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Kajary, Kornelia] Pozitron Diagnosztika KftBudapest, Hungary.
[Nemes, Karolina] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
RP Bardi, E (reprint author), University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, Debrecen, Hungary.
EM editbardi@hotmail.com
CR London K, Cross S, Onikul E, Dalla-Pozza L, Howman-Giles R, 2011,, 18)F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging. Eur J Nucl Med Mol Imaging 38:274–284
Rhodes MM, Delbeke D, Whitlock JA, Martin W, Kuttesch JF, Frangoul HA, Shankar S, 2006, Utility of FDG-PET/CT in follow up of children treated for Hodgkin and non-Hodgkin lymphoma. J Pediatr Hematol Oncol 28:300–306
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 139
EP 143
DI 10.1007/s12253-013-9676-3
PG 5
ER
PT J
AU Arzt, L
Quehenberger, F
Halbwedl, I
Mairinger, Th
Popper, HH
AF Arzt, Lisa
Quehenberger, Franz
Halbwedl, Iris
Mairinger, Thomas
Popper, H Helmut
TI BAP1 Protein is a Progression Factor in Malignant Pleural Mesothelioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BRCA1-associated protein1 (BAP1); Malignant pleuralmesothelioma; Asbestos exposure; Overall survival
ID BRCA1-associated protein1 (BAP1); Malignant pleuralmesothelioma; Asbestos exposure; Overall survival
AB Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time - the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to nonasbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.
C1 [Arzt, Lisa] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, 8036 Graz, Austria.
[Quehenberger, Franz] Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Auenbruggerplatz 2/V, 8036 Graz, Austria.
[Halbwedl, Iris] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, 8036 Graz, Austria.
[Mairinger, Thomas] Helios Klinikum Berlin, Institute of Pathology, Walterhoferstraße 11, 14156 Berlin, Germany.
[Popper, H Helmut] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, 8036 Graz, Austria.
RP Arzt, L (reprint author), Medical University of Graz, Department of Pathology, 8036 Graz, Austria.
EM lisa.arzt@medunigraz.at
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 145
EP 151
DI 10.1007/s12253-013-9677-2
PG 7
ER
PT J
AU Catrina (Ene), MA
Borze, I
Guled, M
Costache, M
Leen, G
Sajin, M
Ionica, E
Chitu, A
Knuutila, S
AF Catrina (Ene), Maria Ana
Borze, Ioana
Guled, Mohamed
Costache, Mariana
Leen, Gayle
Sajin, Maria
Ionica, Elena
Chitu, Aura
Knuutila, Sakari
TI MicroRNA Expression Profiles in Kaposi’s Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Array profiling; FFPE; Kaposi sarcoma; miRNA; Quantitative reverse transcriptase polymerase chain reaction
ID Array profiling; FFPE; Kaposi sarcoma; miRNA; Quantitative reverse transcriptase polymerase chain reaction
AB Kaposi’s sarcoma (KS) is a mesenchymal tumor, caused by Human herpesvirus 8 (HHV8) with molecular and cytogenetic changes poorly understood. To gain further insight on the underlying molecular changes in KS, we performed microRNA (miRNA) microarray analysis of 17 Kaposi’s sarcoma specimens. Three normal skin specimens were used as controls. The most significant differentially expressed miRNA were confirmed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We detected in KS versus normal skin 185 differentially expressed miRNAs, 76 were upregulated and 109 were downregulated. The most significantly downregulated miRNAs were miR-99a, miR- 200 family, miR-199b-5p, miR-100 and miR-335, whereas kshv-miR-K12-4-3p, kshv-miR-K12-1, kshv-miR-K12-2, kshv-miR-K12-4-5p and kshv-miR-K12-8 were significantly upregulated. High expression levels of kshv-miR-K12-1 (p=0.004) and kshv-miR-K12-4-3p (p=0.001) was confirmed by RT-PCR. The predicted target genes for differentially expressed miRNAs included genes which are involved in a variety of cellular processes such as angiogenesis (i.e. THBS1) and apoptosis (i.e. CASP3, MCL1), suggesting a role for these miRNAs in Kaposi’s sarcoma pathogenesis.
C1 [Catrina (Ene), Maria Ana] University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, 050095 Bucharest, Romania.
[Borze, Ioana] University of Helsinki, Haartman Institute and HUSLAB, Department of Pathology, Haartmaninkatu 3, 00014 Helsinki, Finland.
[Guled, Mohamed] University of Helsinki, Haartman Institute and HUSLAB, Department of Pathology, Haartmaninkatu 3, 00014 Helsinki, Finland.
[Costache, Mariana] Department of Pathology, 050471 Bucharest, Romania.
[Leen, Gayle] University of Helsinki, Haartman Institute and HUSLAB, Department of Pathology, Haartmaninkatu 3, 00014 Helsinki, Finland.
[Sajin, Maria] Department of Pathology, 050471 Bucharest, Romania.
[Ionica, Elena] University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, 050095 Bucharest, Romania.
[Chitu, Aura] University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, 050095 Bucharest, Romania.
[Knuutila, Sakari] University of Helsinki, Haartman Institute and HUSLAB, Department of Pathology, Haartmaninkatu 3, 00014 Helsinki, Finland.
RP Knuutila, S (reprint author), University of Helsinki, Haartman Institute and HUSLAB, Department of Pathology, 00014 Helsinki, Finland.
EM sakari.knuutila@helsinki.fi
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 153
EP 159
DI 10.1007/s12253-013-9678-1
PG 7
ER
PT J
AU Zhang, J
Xu, H
Ren, F
Yang, Y
Chen, B
Zhang, F
AF Zhang, Jinnan
Xu, Haiyan
Ren, Fang
Yang, Yijin
Chen, Bin
Zhang, Fengchun
TI Analysis of Clinicopathological Features and Prognostic Factors of Desmoplastic Small Round Cell Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Desmoplastic small round cell tumor; Prognosis
ID Desmoplastic small round cell tumor; Prognosis
AB Desmoplastic small round cell tumor (DSRCT) is a relatively uncommon and highly aggressive malignancy in young males. It is associated with a poor outcome, due in part to missed diagnosis. To characterize the clinical pathological features of DSRCT in Chinese patients and to find out the characteristics of treatment and prognostic factors, the authors collected and analyzed the clinical information of 48 cases. A total of 48 cases of DSRCT between March 1995 and March 2012were retrospectively reviewed and analyzed. The clinical information, histological results and survival data of the patients were collected. Median age was 26.96±14.09 years with a range of 6–66 years. Thirty-three patients (68.75 %) were seen before 30 years old, and 15 patients (31.25 %) were diagnosed after 30 years old. The male-to-female ratio is 3.36 :1. Among them, 37 cases presented with tumors in the abdominal or pelvic cavity; the other 11 cases had extraabdominal tumors. The most common symptoms were abdominal pain (19/48, 39.58 %) and palpable mass (12/48, 25.00 %). The percentage of patients received surgery, complete surgery, and chemotherapy was 79.17 %, 37.50 %, and 52.08 %, respectively. Median follow-up duration was 2.67 years. Median overall survival for all patients was 24.33 months (95 % CI: 9.74–38.92 months) and median event-free survival for all patients was 8.00 months (95 % CI: 5.13–10.89 months). Univariate analysis revealed that surgery, effective debulking surgery, chemotherapy and any two or more combined therapeutics were significant prognostic factors for longer overall survival (p<0.05). Cox regression analysis showed complete surgery was an independent prognostic factor. Standard therapy for DSRCT consists of combination of surgical resection and postoperative chemotherapy. Complete surgery is an independent prognostic factor and should be further investigated.
C1 [Zhang, Jinnan] Jilin University, China-Japan Union Hospital, Department of Neurosurgery, 130031 Changchun, China.
[Xu, Haiyan] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
[Ren, Fang] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
[Yang, Yijin] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
[Chen, Bin] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
[Zhang, Fengchun] Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
RP Zhang, F (reprint author), Shanghai Jiaotong University School of Medicine, Suzhou Kowloon Hospital, Department of Oncology, 215021 Suzhou, China.
EM fczhang2004@163.com
CR Gerald WL, Rosai J, 1989, Case 2: desmoplastic small round cell tumor with divergent differentiation. Pediatr Pathol 9:177–183
Dufresne A, Cassier P, Couraud L, Marec-Berard P,Meeus P, Alberti L, Blay JY, 2012, Desmoplastic small round cell tumor: current management and recent findings. Sarcoma 2012:714986
Rekhi B, Ahmed S, Basak R, Qureshi SS, Desai SS, Ramadwar M, Desai SB, Kurkure P, Jambhekar NA, 2012, Desmoplastic small round cell tumor-clinicopathological spectrum, including unusual features and immunohistochemical analysis of 45 tumors diagnosed at a tertiary cancer referral centre, with molecular results t(11; 22,, p13; q12,, EWS-WT1, in select cases. Pathol Oncol Res 18:917– 927
Gerald WL, Ladanyi M, de Alava E , Cuatrecasas M, Kushner BH, LaQuaglia MP, Rosai J, 1998, Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16:3028–3036
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Hayes-Jordan A, Anderson PM, 2011, The diagnosis and management of desmoplastic small round cell tumor: a review. Curr Opin Oncol 23:385–389
Kushner BH, LaQuaglia MP, Wollner N, Meyers PA, Lindsley KL, Ghavimi F, Merchant TE, Boulad F, Cheung NK, Bonilla MA, Crouch G, Kelleher JF Jr, Steinherz PG, Gerald WL, 1996, Desmoplastic small round cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol 14:1515–1531
Bertuzzi A, Castagna L, Nozza A, Quagliuolo V, Siracusano L, Balzarotti M, Compasso S, Alloisio M, Soto Parra H, Santoro A, 2002, High-dose chemotherapy in poor-prognosis adult small round cell tumours: clinical and molecular results from a prospective study. J Clin Oncol 20:2181–2188
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Watanabe T, Miyamoto S, Kitagori K, Horimatsu T, Morita S, Mashimo Y, Ezoe Y, Muto M, Chiba T, 2012, A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy. Oncol Lett 3:30–34
Quaglia MP, Brennan MF, 2000, The clinical approach to desmoplastic small round cell tumor. Surg Oncol 9:77–81
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 161
EP 168
DI 10.1007/s12253-013-9679-0
PG 8
ER
PT J
AU Maraz, R
Boross, G
Pap-Szekeres, J
Rajtar, M
Ambrozay,
Cserni, G
AF Maraz, Robert
Boross, Gabor
Pap-Szekeres, Jozsef
Rajtar, Maria
Ambrozay, Eva
Cserni, Gabor
TI Internal Mammary Sentinel Node Biopsy in Breast Cancer. Is it Indicated?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Internalmammary nodes; Sentinel node biopsy
ID Breast cancer; Internalmammary nodes; Sentinel node biopsy
AB Axillary sentinel node (A-SN) biopsy is a standard procedure in breast cancer surgery. Sampling of intenal mammary sentinel nodes (IM-SN) is not performed routinly, although it is also considered an important prognostic factor of breast cancer. The role of this latter procedure was investigated in cases of IM-SN visualized on lymphoscintigraphy. Between January 2001 and June 2012 1542 patients with clinically node negative operable primary breast cancer had sentinel node biopsy (SNB). Both axillary and IM-SN were sampled (whenever detected), based on lymphoscintigraphy, intraoperative gamma probe detection and blu dye mapping. Lymphoscintigraphy showed IM-SN in 83 cases. IM-SN biopsy (IM-SNB) was succesfull in 77 patients (93 %). A total of 86 IM-SNs were removed. IM-SN involvement was identified in 14 cases, representing 18 % of patients who underwent IM-SNB. This included macrometastases (MAC) in 5 cases, micrometastases (MIC) in 2 cases, isolated tumor cells (ITC) in 7 cases. No significant differences were found between patients with and without IM-SN involvement in terms of age, tumor location, tumor size, axillary involvement, tumor grade or estrogen receptor status. The IM-SN involvement has lead to new therapeutic indications in 2 cases (2.6 %), both of them due to MAC in the IM-SN: in 1 case change in chemotherapy and in 1 case change in radiotherapy, with the addition of iradiation of the internal mammary chain. Based on this series and information from the literature, we conclude that the indication for an IM-SNB procedure is very limited and its routine use should not be recommended.
C1 [Maraz, Robert] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Boross, Gabor] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Pap-Szekeres, Jozsef] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Rajtar, Maria] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Ambrozay, Eva] Bacs-Kiskun County Teaching Hospital, Breast Diagnostic UnitKecskemet, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of PathologyKecskemet, Hungary.
RP Maraz, R (reprint author), Bacs-Kiskun County Hospital, Department of Surgery, 6000 Kecskemet, Hungary.
EM marazrobert2010@gmail.com
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Uren RF, Howman-Giles RB, Thompson JF et al, 1995, Mammary lymphoscintigraphy in breast cancer. J Nucl Med 36:1775–1780
Lamonica D, Edge SB, Hurd T et al, 2003, Mammographic and clinical predictors of drainage patterns in breast lymphoscintigrams obtained during sentinel node procedures. Clin NuclMed 28:558–564
Van der Ent FW, Kengen RA, van der Pol HA et al, 2001, Halsted revisited: internal mammary sentinel lymph node biopsy in breast cancer. Ann Surg 234:79–84
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Cserni G, 2002, Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 55:926–931
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Heuts EM, van der Ent FW, Hulsewe KWE, von Meyenfeldt MF, Voogd EM, 2009, Internal mammary lymph drainage and sentinel node biopsy in breast cancer- A study on 1008 patients. Eur J Cancer Surgery 35:252–257
Nathan J, Boyages J, French JR, Ung OA, 2008, Internal mammary sentinel nodes: ignore, irradiate or operate? Eur J Cancer 45:789–794
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Roumen RMH, Geuskens LM, Valkenburg JGH et al, 1999, In search of the true sentinel node by different injection techniques in breast cancer patients. Eur J Surg Oncol 25:347–351
Borgstein PJ, Meijer S, Pijpers RJ, van Diest PJ, 2000, Functional lymphatic anatomy for sentinel node biopsy in breast cancer: echoes from the past and the periareolar blue method. Ann Surg 1(81–89)
Spillane AJ, Noushi F, Cooper RA, Gebski V, Uren RF, 2009, Highresolution lymphoscintigraphy is essential for recognition of the significance of internal mammary nodes in breast cancer. Ann Oncol 20:977–984
Sugg SL, Ferguson DJ, Posner MC, Heimann R, 2000, Should internal mammary nodes be sampled in the sentinel lymph node era? Ann Surg Oncical Oncol 7:188–192
Van der Ent FW, Kengen RA, van der Pol HA, Povel JA, Stroeken HJ, Hoofwijk AG, 2001, Halsted revisited: internal mammary sentinel lymph node biopsy in breast cancer. Ann Surg 234(1):79–84
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 169
EP 177
DI 10.1007/s12253-013-9680-7
PG 9
ER
PT J
AU Feng, Qj
Zhang, F
Huang, Xy
Wu, Zx
AF Feng, Qing-jing
Zhang, Feng
Huang, Xiao-yun
Wu, Zhi-xiang
TI Effectiveness and Complications of Anthracycline and Taxane in the Therapy of Breast Cancer: A Meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Meta-analysis; Breast cancer; Anthracycline; Taxane
ID Meta-analysis; Breast cancer; Anthracycline; Taxane
AB Objective: To compare the efficacy and safety between anthracycline & taxane and anthracycline in the treatment of breast cancer. Methods: Computer-assisted literature search was performed with PubMed, MEDLINE, EMBASE and Cochrane Controlled Trials Register (CCTR) to identify pertinent literatures. Software RevMan 5.0 was used for statistical analysis. The measurement of interest outcomes included severe neurotoxicity, death without breast cancer recurrences, leukemia, venous thrombus and severe cardiotoxicity. Results: A total of 10 randomized controlled trial studies (RCTs) containing 18,198 cases were selected in this metaanalysis. Of which, 9,902 cases were treated with anthracycline & taxane and 8,296 cases treated with anthracycline alone as control. Anthracycline& taxane showed lower risks of incident leukemia (RR=0.40; 95 % CI: 0.18, 0.90), venous thrombus (RR=0.49; 95 % CI: 0.29, 0.84) and severe cardiotoxicity (RR=0.41, 95%CI: 0.26, 0.66), but higher risks of incident severe neurotoxicity (RR=5.97; 95 % CI: 1.72, 20.65) and non-recurrent death (RR=1.79; 95%CI: 1.06, 3.04), compared to anthracycline alone. Conclusion: Clinically important differences exist for general safety in favour of the anthracycline & taxane rather than anthracycline alone. However, as a result of tumor recurrent rate, anthracycline might be superior to anthracycline & taxane. A longer duration of follow-up and a larger number of cases are required to better assess the efficacy and safety profile of the treatment of breast cancer.
C1 [Feng, Qing-jing] Yiwu Maternity and Child Care Hospital, Department of Breast Surgery, 322000 Yiwu, China.
[Zhang, Feng] School of Medicine, Zhejiang University, Women’s Hospital, Department of Surgery, No. 1 Xueshi Road, 310006 Hangzhou, China.
[Huang, Xiao-yun] Yiwu Maternity and Child Care Hospital, Department of Breast Surgery, 322000 Yiwu, China.
[Wu, Zhi-xiang] Shanghai Jiao Tong University, The International Peace Maternity and Child Health Hospital of China welfare Institute, Department of Breast Surgery, 200030 Shanghai, China.
RP Zhang, F (reprint author), School of Medicine, Zhejiang University, Women’s Hospital, Department of Surgery, 310006 Hangzhou, China.
EM zhang3772@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 179
EP 184
DI 10.1007/s12253-013-9681-6
PG 6
ER
PT J
AU Rehders, A
Anlauf, M
Adamowsky, I
Ghadimi, HM
Klein, S
Antke, Ch
Cupisti, K
Stoecklein, HN
Knoefel, TW
AF Rehders, Alexander
Anlauf, Martin
Adamowsky, Ilona
Ghadimi, H Markus
Klein, Sarah
Antke, Christina
Cupisti, Kenko
Stoecklein, H Nikolas
Knoefel, T Wolfram
TI Is Minimal Residual Lymph Node Disease in Papillary Thyroid Cancer of Prognostic Impact? An Analysis of The Epithelial Cell Adhesion Molecule EpCAM in Lymph Nodes of 40 pN0 Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid cancer; Lymphadenectomy; Radio iodine treatment; Tumor cell dissemination; Immunohistochemistry
ID Papillary thyroid cancer; Lymphadenectomy; Radio iodine treatment; Tumor cell dissemination; Immunohistochemistry
AB This study was aimed to assess the extend of nodal microdissemination in patients with pN0 papillary thyroid carcinoma (PTC) using immunohistochemical analysis. In early stage PTC both, systematic lymphadenectomy as well as radio iodine treatment, aimed to eliminate occult nodal tumor involvement, are under controversial debate, since little is known about the extend of lymphatic microdissemination in these patients. Formalin embedded samples of the resected lymph nodes were systematically screened for the presence of disseminated tumor cells using immunohistochemistry (monoclonal antibody Ber-EP4). Clinical and histopathological parameters as well as the post-operative course were recorded. Survival data were analysed by the Kaplan-Meier method and the log rank test. Overall 321 lymph nodes of 40 patients were screened immunohistochemically. In 12.5 % of the patients disseminated occult tumor cells were diagnosed. In addition to tumor resection 90 % of the patients underwent adjuvant radio-iodine treatment. The mean observation period in our collective was 72 months. The detection of disseminated tumor cells did not correlate with clinicopathologic risk parameters and did not have significant influence on the prognosis of these patients. Immunohistochemical analysis enables the detection of disseminated tumor cells in patients with pN0 PTC. This finding seems to support the application of adjuvant radio iodine, even in early tumor stages.
C1 [Rehders, Alexander] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Anlauf, Martin] Heinrich Heine University, Institute of PathologyDusseldorf, Germany.
[Adamowsky, Ilona] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Ghadimi, H Markus] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Klein, Sarah] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Antke, Christina] Heinrich Heine University, Department of Nuclear MedicineDusseldorf, Germany.
[Cupisti, Kenko] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Stoecklein, H Nikolas] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
[Knoefel, T Wolfram] Heinrich Heine University, Department of SurgeryDusseldorf, Germany.
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Ito Y, Tomoda C, Uruno T et al, 2006, Clinical significance of metastasis to the central compartment frompapillary microcarcinoma of the thyroid. World J Surg 30:91–99
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 185
EP 190
DI 10.1007/s12253-013-9682-5
PG 6
ER
PT J
AU Samulak, D
Grosman-Dziewiszek, P
Michalska, MM
Mojs, E
Samulak, K
Romanowicz, H
Smolarz, B
AF Samulak, Dariusz
Grosman-Dziewiszek, Patrycja
Michalska, M Magdalena
Mojs, Ewa
Samulak, Katarzyna
Romanowicz, Hanna
Smolarz, Beata
TI Evaluation of Expression of the PTEN Gene, Oestrogen and Progesterone Receptors as Diagnostic and Predictive Factors in Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Oestrogen and progesterone receptors; PTEN gene; Predictive factor
ID Endometrial cancer; Oestrogen and progesterone receptors; PTEN gene; Predictive factor
AB Endometrial cancer belongs to the commonest malignancy in females after breast cancer,malignant neoplasm of female genitals in Europe and North America but there is still not significant improvement as far as the curability of this neoplasm is concerned, especially its advanced forms. That is why there is need to define new factors that could be not only diagnostic but also predictve factors. In present study we analyzed the mRNA PTEN expression by quantitative realtime polymerase chain reaction (Q-PCR) in 123 women of endometrial carcinoma and 14 women of control group. Moreover we assessed oestrogen (ER) and progesterone receptors (PgR) in all cases.We defined the correlation between expression of PTEN gene and receptors and between PTEN expression and maturity grade of cancer. Neoplasm advancement grade G1was diagnosed in 82.11%of patients (n =101), G2 in 9.76 % of patients (n =12) and G3 in 8.13 % of patients (n =10). Presence of ER and PgR and decreased expression of PTEN gene was found in majority of patients with endometrial cancer (79.12 % and 59.34 % respectively) and the most numerous group was with weak expression of ER and strong expression of PgR. There was no statistically significant difference in gene expression depending on receptors expression nor maturity grade of cancer (p >0.05). Evaluation of expression of PTEN gene may turn out to be a very useful tool aimed at qualifying patients for different therapies of endometrial cancer and at searching of new diagnostic and therapeutic methods of this cancer independently on its receptor status nor maturity grade of cancer.
C1 [Samulak, Dariusz] Poznan University of Medical Sciences, Cathedral of Mother’s and Child’s Health, ul. Polna 33, 60-535 Poznan, Poland.
[Grosman-Dziewiszek, Patrycja] Wroclaw Medical University, Department of Human Morphology and Embryology, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Michalska, M Magdalena] Regional Hospital in Kalisz, Department of Obstetrics and Gynaecology, ul. Torunska 7, 62-800 Kalisz, Poland.
[Mojs, Ewa] Poznan University of Medical Sciences, Department of Clinical PsychologyPoznan, Poland.
[Samulak, Katarzyna] University of Medical Sciences in Poznan, Student Scientific Society, ul. Polna 33, 60-535 Poznan, Poland.
[Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
RP Smolarz, B (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, 93-338 Lodz, Poland.
EM smolbea@wp.pl
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Inaba F, Kawamata H, Teramoto T, Fukasawa I, Inaba N, Fujimori T, 2005, PTEN and p53 abnormalities are indicative and predictive factors for endometrial carcinoma. Oncol Rep 13:17–24
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Sobczuk A, Smolarz B, Romanowicz-Makowska H, Pertynski T, 2006, MMAC/PTEN gene expression in endometrial cancer: RTPCR studies. Pol J Pathol 57:137–140
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Gadducci A, Tana R, Cosio S, Fanucchi A, Genazzani AR, 2008, Molecular target therapies in endometrial cancer: from the basic research to the clinic. Gynecol Endocrinol 24:239–249
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 191
EP 196
DI 10.1007/s12253-013-9684-3
PG 6
ER
PT J
AU Qian, L
Luo, Q
Zhao, X
Huang, J
AF Qian, Liqiang
Luo, Qingquan
Zhao, Xiaojing
Huang, Jia
TI Pathways Enrichment Analysis for Differentially Expressed Genes in Squamous Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Squamous lung cancer; Oncogenesis mechanism; Potential pathways; Target genes
ID Squamous lung cancer; Oncogenesis mechanism; Potential pathways; Target genes
AB Squamous lung cancer (SQLC) is a common type of lung cancer, but its oncogenesis mechanism is not so clear. The aim of this study was to screen the potential pathways changed in SQLC and elucidate the mechanism of it. Published microarray data of GSE3268 series was downloaded from Gene Expression Omnibus (GEO). Significance analysis of microarrays was performed using software R, and differentially expressed genes (DEGs) were harvested. The functions and pathways of DEGs were mapped in Gene Otology and KEGG pathway database, respectively. A total of 2961 genes were filtered as DEGs between normal and SQLC cells. Cell cycle and metabolism were the mainly changed functions of SQLC cells. Meanwhile genes such as MCM, RFC, FEN1, and POLD may induce SQLC through DNA replication pathway, and genes such as PTTG1, CCNB1, CDC6, and PCNA may be involved in SQLC through cell cycle pathway. It is demonstrated that pathway analysis is useful in the identification of target genes in SQLC.
C1 [Qian, Liqiang] Shanghai JiaoTong University, Shanghai Chest Hospital, Shanghai Lung Cancer Center, NO.241 Huaihai Road, 200030 Shanghai, China.
[Luo, Qingquan] Shanghai JiaoTong University, Shanghai Chest Hospital, Shanghai Lung Cancer Center, NO.241 Huaihai Road, 200030 Shanghai, China.
[Zhao, Xiaojing] Shanghai JiaoTong University, Shanghai Chest Hospital, Shanghai Lung Cancer Center, NO.241 Huaihai Road, 200030 Shanghai, China.
[Huang, Jia] Shanghai JiaoTong University, Shanghai Chest Hospital, Shanghai Lung Cancer Center, NO.241 Huaihai Road, 200030 Shanghai, China.
RP Luo, Q (reprint author), Shanghai JiaoTong University, Shanghai Chest Hospital, Shanghai Lung Cancer Center, 200030 Shanghai, China.
EM luoqingquanlqq@hotmail.com
CR Tseng C-Y, Huang Y-C, Su S-Y, Huang J-Y, Lai C-H, Lung C-C, Ho C-C, Liaw Y-P, 2012, Cell type specificity of female lung cancer associated with sulfur dioxide from air pollutants in Taiwan: an ecological study. BMC Publ Health 12(1):4
Giangreco A, Lu L, Vickers C, Teixeira VH, Groot KR, Butler CR, Ilieva EV, George PJ, Nicholson AG, Sage EK, 2012, β–Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial–mesenchymal transition. J Pathol 226(4):575–587
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Li C, Johnson DE, 2013, Liberation of functional p53 by proteasome inhibition in human papilloma virus-positive head and neck squamous cell carcinoma cells promotes apoptosis and cell cycle arrest. Cell Cycle 12(6)
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 197
EP 202
DI 10.1007/s12253-013-9685-2
PG 6
ER
PT J
AU Chen, XJ
Shen, J
Zhang, GB
Chen, WCh
AF Chen, Xiao-Juan
Shen, Jin
Zhang, Guang-Bo
Chen, Wei-Chang
TI B7-H6 Protein Expression has no Prognostic Significance in Human Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B7-H6; Gastric carcinoma; Adjacent non-tumor tissues; Immunohistochemistry
ID B7-H6; Gastric carcinoma; Adjacent non-tumor tissues; Immunohistochemistry
AB B7-H6, a novel member of the B7 family which binds to NKp30 to trigger antitumor NK cell cytotoxicity and cytokine secretion. Recently, B7-H family has been reported to be a negative regulator of the immune response in patients with gastric carcinoma.However, no reports have investigated the clinical significance of B7-H6 expression in human gastric cancer. We present the first study to the clinicopathological and prognostic value of B7-H6 in primary gastric tumors and adjacent non-tumor tissues at the protein level. Here we show that B7-H6 immunoreactivity was expressed in 6/60 (10 %) gastric tumors and 8/43 (18.60 %) adjacent non-tumor tissues. No statistical difference was found between B7-H6 expression and various prognostic factors; however, B7-H6-positive carcinomas were significantly associated with a higher differentiation (p =0.047). The survival analysis did not confirm the prognostic significance of B7-H6 expression in gastric cancer patients. Our data suggest that B7-H6, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer.
C1 [Chen, Xiao-Juan] The First Affiliated Hospital of Soochow University, Department of Gastroenterology, 215006 Suzhou, China.
[Shen, Jin] The First Affiliated Hospital of Soochow University, Department of Gastroenterology, 215006 Suzhou, China.
[Zhang, Guang-Bo] The First Affiliated Hospital of Soochow University, Department of Gastroenterology, 215006 Suzhou, China.
[Chen, Wei-Chang] The First Affiliated Hospital of Soochow University, Department of Gastroenterology, 215006 Suzhou, China.
RP Chen, WCh (reprint author), The First Affiliated Hospital of Soochow University, Department of Gastroenterology, 215006 Suzhou, China.
EM chenwcdoc@163.com
CR Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA Cancer Clin 61:69–90., DOI 10.3322/caac
Zang X, Allison JP, 2007, The B7 family and cancer therapy. Costimulation and coinhibition. Clin Cancer Res 13:5271–5279
Greaves P, Gribben JG, 2013, The role of B7 family molecules in hematologic malignancy. Blood 121:734–744., DOI 10.1182/blood- 2012-10-385591
Lu B, Chen L, Liu L, Zhu Y, Wu C, Jiang J, Zhang X, 2011, T-cellmediated tumor immune surveillance and expression of B7 coinhibitory molecules in cancers of the upper gastrointestinal tract. Immunol Res 50:269–275., DOI 10.1007/s12026-011-8227-9
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Seliger B, Quandt D, 2012, The expression, function, and clinical relevance of B7 family members in cancer. Cancer Immunol Immunother 61:1327–1341., DOI 10.1007/s00262-012-1293-6
Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B, Haldeman B, Ostrander CD, Kaifu T, Chabannon C, Moretta A,West R, XuW, Vivier E, Levin SD, 2009, The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med 206:1495–1503., DOI 10.1084/ jem.20090681
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, 2009, AJCC cancer staging manual, 7th edn. Springer-verlag, New York
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Arigami T, Uenosono Y, Hirata M, Yanagita S, Ishigami S, Natsugoe S, 2011, B7-H3 expression in gastric cancer: a novel molecular blood marker for detecting circulating tumor cells. Cancer Sci 102:1019–1024., DOI 10.1111/j.1349-7006.2011. 01877.x
Arigami T, Uenosono Y, Ishigami S, Hagihara T, Haraguchi N, Natsugoe S, 2011, Clinical significance of the B7-H4 coregulatory moleculeas a novel prognostic marker in gastric cancer. World J Surg 35:2051–2057., DOI 10.1007/s00268-011- 1186-4
Jiang J, Zhu Y,Wu C, Shen Y,WeiW, Chen L, ZhengX, Sun J, Lu B, Zhang X, 2010, Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer. Cancer Immunol Immunother 59:1707–1714
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 203
EP 207
DI 10.1007/s12253-013-9686-1
PG 5
ER
PT J
AU Yerrabothala, S
Shaaban, H
Capo, G
Maroules, M
Debari, AV
AF Yerrabothala, Swaroopa
Shaaban, Hamid
Capo, Gerardo
Maroules, Michael
Debari, A Vincent
TI The Impact of Diabetes Mellitus on Breast Cancer Outcomes: A Single Center Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Practice Guideline
DE Diabetes mellitus; Breast neoplasms; Survival
ID Diabetes mellitus; Breast neoplasms; Survival
AB Diabetes mellitus has been implicated to affect the prognostic outcomes of patients with various types of cancer. This study explores the impact of diabetes mellitus on the survival outcomes of patients with all stages of breast cancer. We performed a retrospective analysis of 255 patients with all stages of breast cancer. Survival outcomes were compared for diabetic and non-diabetic patients. A greater percent of patients in the non-diabetic group (54.1 %) presented with early-stage (stage 0 and 1) cancer than diabetics for which 41.2 % presented with stage 0 or 1 breast cancer; however this difference did not achieve statistical significance (p=0.068). Overall, we observed a significant difference in survival between the diabetics and non-diabetic subjects (p=0.001). Even after adjustment for all covariates and after stratification for Body Mass Index (BMI), diabetics were found to have a poorer prognosis in terms of survival time. In patients with breast cancer, diabetes mellitus is an independent predictor of lower overall survival rates, even after adjusting for other comorbidities. Primary caregivers and oncologists alike should aggressively screen breast cancer patients for diabetes mellitus and vice versa.
C1 [Yerrabothala, Swaroopa] Seton Hall University School of Health and Medical Sciences, Trinitas Regional Medical CenterElizabeth, USA.
[Shaaban, Hamid] St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 111 central avenue, 07102 Newark, NJ, USA.
[Capo, Gerardo] Seton Hall University School of Health and Medical Sciences, Trinitas Regional Medical CenterElizabeth, USA.
[Maroules, Michael] Seton Hall University School of Health and Medical Sciences, St Joseph’s Regional Medical CenterPaterson, USA.
[Debari, A Vincent] Seton Hall University School of Health and Medical SciencesSouth Orange, NJ, USA.
RP Shaaban, H (reprint author), St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 07102 Newark, USA.
EM hamidshaaban@gmail.com
CR American Cancer Society, 2008, Breast cancer facts and figures 2007–2008. American Cancer Society, Atlanta
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 209
EP 214
DI 10.1007/s12253-013-9666-5
PG 6
ER
PT J
AU Fernandez-Vega, I
Quirk, J
Norwood, LF
Sibtain, AN
Laxton, R
Bodi, I
AF Fernandez-Vega, Ivan
Quirk, Jennifer
Norwood, L Fiona
Sibtain, A Naomi
Laxton, Ross
Bodi, Istvan
TI Gliomatosis Cerebri Type 1 with Extensive Involvement of the Spinal Cord and BRAF V600E Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Gliomatosis cerebri; BRAF V600E; Brain; Spinal cord
ID Glioma; Gliomatosis cerebri; BRAF V600E; Brain; Spinal cord
AB Gliomatosis cerebri (GC) is a rare neoplasm in which there is a diffuse cerebral infiltration by malignant glial cells with relative conservation of the underlying structures. A 67-year-old lady was admitted complaining of balance problems, troubled breathing, stuttered speech, decreased mobility, progressive ataxia and also some mild cognitive problems. MRI demonstrated ill defined T2 hyperintensity with mild mass effect mainly involving the brain stem and cerebellar hemispheres, with minor signal abnormalities extending supratentorially along the corticospinal tracts. The imaging appearances were static over a year. No biopsy was performed. The patient received palliative care and died 2 years after initial presentation. Macroscopic examination of the brain showed an extensive firm white-grey lesion predominantly in the cerebellar white matter, the brainstem, spreading to the full length of the spinal cord and invading the sensory ganglia. Histology revealed an extensively infiltrating diffuse glioma with small elongated fusiform nuclei. Diagnosis of GC type 1 was made. Molecular genetic tests revealed BRAF V600E mutation, while no IDH1 & IDH2 mutations were found. GC should be taken into account in the differential diagnoses mainly when there is rapid clinical deterioration without clear evidence of radiological progression. Extensive spinal cord infiltration has been reported only in 9 % and BRAF V600E mutation was detected only in one case in GC previously. Future clinical trials should address whether BRAF V600E mutant brain tumour patients will benefit from BRAF V600E-directed targeted therapies.
C1 [Fernandez-Vega, Ivan] Hospital Universitario Central de Asturias, Department of PathologyOviedo, Spain.
[Quirk, Jennifer] Princess Royal University Hospital, Department of NeurologyOrpington, UK.
[Norwood, L Fiona] Princess Royal University Hospital, Department of NeurologyOrpington, UK.
[Sibtain, A Naomi] King’s College Hospital, Department of NeuroradiologyLondon, UK.
[Laxton, Ross] King’s College Hospital, Clinical NeuropathologyLondon, UK.
[Bodi, Istvan] King’s College Hospital, Clinical NeuropathologyLondon, UK.
RP Bodi, I (reprint author), King’s College Hospital, Clinical Neuropathology, London, UK.
EM istvan.bodi@nhs.net
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Desestret V, Ciccarino P, Ducray F, Criniere E, Boisselier B, Labussiere M, Polivka M, Idbaih A, Kaloshi G, von Deimling A, Hoang-Xuan K, Delattre JY,Mokhtari K, SansonM(2011, Prognostic stratification of gliomatosis cerebri by IDH1 R132H and INA expression. J Neurooncol 105(2):219–224., DOI 10.1007/s11060-011-0587-4
Kwon MJ, Kim ST, Kong DS, Lee D, Park S, Kang SY, Song JY, Nam DH, Kato Y, Choi YL, Suh YL, 2012, Mutated IDH1 is a favorable prognostic factor for type 2 gliomatosis cerebri. Brain Pathol 22(3):307–317., DOI 10.1111/j.1750-3639.2011.00532.x
Mawrin C, Kirches E, Schneider-Stock R, Boltze C, Vorwerk CK, vonMawrin A, vonDeimling A, Stoltenburg-Didinge G, Bornemann A, Romeike B, Sellhaus B, Dietzmann K, 2005, Alterations of cell cycle regulators in gliomatosis cerebri. J Neurooncol 72(2):115–122., DOI 10.1007/s11060-004-2061-z
LiuW, Lv G, Li Y, Li L,Wang B, 2011, Downregulation of CDKN2A and suppression of cyclin D1 gene expressions in malignant gliomas. J Exp Clin Cancer Res 30:76., DOI 10.1186/1756-9966-30-76
Di Giovanni S,Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI, 2005, Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci U S A 102(23):8333–8338., DOI 10. 1073/pnas.0500989102
Kouri FM, Jensen SA, Stegh AH, 2012, The role of Bcl-2 family proteins in therapy responses ofmalignant astrocytic gliomas: Bcl2L12 and beyond. Sci World J 2012:838916., DOI 10.1100/2012/838916
Mawrin C, Lins H, Kirches E, Schildhaus HU, Scherlach C, Kanakis D, Dietzmann K, 2003, Distribution of p53 alterations in a case of gliomatosis cerebri. Hum Pathol 34(1):102–106., DOI 10.1053/hupa. 2003.1
Wan PTGM, Roe SM, Lee S, NiculescuDuvaz D, Good VM, Jones CM, Marshall CJ, Springer CJBD, Marais R, 2004, Cancer genome project.Mechanismof activation of the RAF-ERKsignaling pathway by oncogenic mutations of B-RAF. Cell 116:855–867., DOI 10.1016/ S0092-8674(04)00215-6
Capper D, Berghoff AS, von DeimlingA, PreusserM(2012, Clinical neuropathology practice news 2-2012: BRAF V600E testing. Clin Neuropathol 31(2):64–66
Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold- Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis DN, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A, 2011, Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121(3): 397–405., DOI 10.1007/s00401-011-0802-6
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Huillard E, Hashizume R, Phillips JJ, Griveau A, Ihrie RA, Aoki Y, Nicolaides T, Perry A, Waldman T, McMahon M, Weiss WA, Petritsch C, James CD, Rowitch DH, 2012, Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy. Proc Natl Acad Sci U S A 109(22):8710–8715., DOI 10.1073/pnas.1117255109
Nicolaides TP, Li H, Solomon DA, Hariono S, Hashizume R, Barkovich K, Baker SJ, Paugh BS, Jones C, Forshew T, Hindley GF, Hodgson JG, Kim JS, Rowitch DH, Weiss WA, Waldman TA, James CD, 2011, Targeted therapy for BRAFV600E malignant astrocytoma. Clin Cancer Res 17(24):7595–7604., DOI 10.1158/ 1078-0432.CCR-11-1456
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 215
EP 220
DI 10.1007/s12253-013-9732-z
PG 6
ER
PT J
AU Kim, SM
Yoo, JN
Lee, HS
AF Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Expressional and Mutational Analysis of CREBBP Gene in Gastric and Colorectal Cancers with Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kim, Sung Min] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Cancer Research Institute, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Cancer Research Institute, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Gonzalez GA, Montminy MR, 1989, Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59:675–680
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Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S, 1998, A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58: 5248–5257
Kim MS, Hur SY, Yoo NJ, Lee SH, 2010, Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol 221:147–152
Kim MS, Oh JE, Kim YR, Park SW, Kang MR, Kim SS, Ahn CH, Yoo NJ, Lee SH, 2010, Somatic mutations and losses of expression of microRNA regulation-related genes AGO2 and TNRC6A in gastric and colorectal cancers. J Pathol 221:139–146
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2014
VL 20
IS 1
BP 221
EP 222
DI 10.1007/s12253-013-9668-3
PG 2
ER
PT J
AU Reptova, S
Trtkova, SK
Kolar, Z
AF Reptova, Silvie
Trtkova, Smesny Katerina
Kolar, Zdenek
TI Direct Detection of the AR-E211 G>A Gene Polymorphism from Blood and Tissue Samples Without DNA Isolation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gene polymorphism; Prostate cancer; Androgen receptor; Direct method
ID Gene polymorphism; Prostate cancer; Androgen receptor; Direct method
AB The pathogenesis of prostate cancer (CaP) involves alterations in a gene structure of the androgen receptor (AR). The single nucleotide polymorphism AR-E211 G>A localized in exon 1 of the AR gene (G1733A) was detected using direct polymerase chain reaction and restriction digestion (PCRRFLP) method on blood and tissue samples without prior DNA isolation. We used blood samples of patients with a diagnosis of benign prostatic hyperplasia (BPH) or CaP. From monitored group of CaP patients were selected specimen in formalin-fixed paraffin-embedded tissue blocks with morphology of BPH and CaP. The main objective of our study was to develop a method based the direct PCR-RFLP analysis from blood and tissue without prior DNA isolation for faster genotyping analysis of a large number of samples. We found no statistically significant differences in allelic % of the ARE211 G>A polymorphism between BPH and CaP patients (p≤0.8462). Genotyping of the AR-E211 G>A variant in blood was not identical with tumor tissue genotyping analysis. Significant agreement between blood and tissue AR-E211 G>A polymorphism only in non-tumor tissue focus was confirmed. Although we analyzed a limited number of the tissue samples, we suppose that a presence of the minor allele A may be associated with cancer transformation-induced changes of the modified AR gene.
C1 [Reptova, Silvie] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
[Trtkova, Smesny Katerina] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
[Kolar, Zdenek] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
RP Trtkova, SK (reprint author), Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, 775 15 Olomouc, Czech Republic.
EM trtkova@post.cz
CR Casella R, Maduro MR, Lipshultz LI, Lamb DJ, 2001, Significance of the polyglutamine tract polymorphism in the androgen receptor. Urology 5:651–656
Gottlieb B, Beitel LK, Wu JH, Trifiro M, 2004, The androgen receptor gene mutations database, ARDB): 2004 update.Hum Mutat 23:527–533
Beilin J, Ball EMA, Favaloro JM, Zajac JD, 2000, Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specifity in prostate and non-prostate cell lines. J Mol Endocrinol 25:85–96
Zitzmann M, Nieschlag E, 2003, The CAGrepeat polymorphismwithin the androgen receptor gene and maleness. Int J Androl 26:76–83
Chang BL, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A et al, 2002, Polymorphic GGC repeats in the androgen receptor gene are associated with hereditary and sporadic prostate cancer risk. Hum Genet 110:122–129
Chen C, Lamharzi N, Weiss NS, Etzioni R, Dightman DA, Barnett et al, 2002, Androgen receptor polymorphisms and the incidence of prostate cancer. Cancer Epidemiol Biomarkers Prev 11:985–986
Ferro P, Catalano MG, Dell’Eva R, Fortunati N, Pfeffer U, 2002, The androgen receptor CAG repeat: a modifier of carcinogenesis? Mol Cell Endocrinol 193:109–120
Mononen N, Ikonen T, Autio V, Rokman A, Matikainen MP, Teuvo L et al, 2002, Androgen receptor CAG polymorphism and prostate cancer risk. Hum Genet 111:166–171
Silva NB, Koff WJ, Biolchi V, Brenner C, Biolo KD, Spritzer PM et al, 2008, Polymorphic CAG and GGC repeat lengths in the androgen receptor gene and prostate cancer risk: analysis of a Brazilian population. Cancer Invest 26:74–80
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Ross RK, Pike MC, Coetzee GA, Reichardt JKV, Yu MC, Feigelson H, 1998, Androgen metabolism and prostate cancer: Establishing a model of genetic susceptibility. Cancer Res 58:4497– 4504
Gray IC, Campbell DA, Spurr NK, 2000, Single nucleotide polymorphisms as tools in human genetics. Hum Mol Genet 9:2403– 2408
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Sasaki M, Karube A, Karube Y,Watari M, Sakuragi N, Fujimoto S, Dahiya R, 2005, GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients. Biochem Biophys Res Commun 329:100–104
Hayes VM, Severi G, Eggleton SA, Padilla EJD, Southey MC, Sutherland RL, Hopper JL, Giles GG, 2005, The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. Cancer Epidemiol Biomarkers Prev 14:993–996
Medeiros R, Vasconcelos A, Costa S, Pinto D, Morais A, Oliveira J, Lopees C, 2003, Steroid hormone genotypes ARStuI and ER325 are linked to the progression of human prostate cancer. Cancer Genet Cytogenet 141:91–96
Ribeiro ML, Santos A, Carvalho-Salles AB, Hackel C, 2002, Allelic frequencies of six polymorphic markers for risk of prostate cancer. Braz J Med Biol Res 35:205–213
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 223
EP 227
DI 10.1007/s12253-013-9671-8
PG 5
ER
PT J
AU Liu, Ch
Cui, Q
Guo, J
Li, D
Zeng, Y
AF Liu, Cheng
Cui, Qiu
Guo, Jun
Li, Dingfeng
Zeng, Yanjun
TI Intra-Arterial Intervention Chemotherapy for Sarcoma and Cancerous Ulcer Via an Implanted Pump
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sarcoma ulcer; Cancerous ulcer; Chemotherapy pump; Intra-arterial chemotherapy
ID Sarcoma ulcer; Cancerous ulcer; Chemotherapy pump; Intra-arterial chemotherapy
AB To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limbsalvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms including pain, infection and bleeding, which would help to make a decreased blood supplied and well defined tumor boundary to finally decrease the recurrence rate.
C1 [Liu, Cheng] Affiliated Hospital of Academy of Military Medical Sciences, Department of Orthopedics (307 Hospital of PLA), 100071 Beijing, China.
[Cui, Qiu] Affiliated Hospital of Academy of Military Medical Sciences, Department of Orthopedics (307 Hospital of PLA), 100071 Beijing, China.
[Guo, Jun] Affiliated Hospital of Academy of Military Medical Sciences, Department of Orthopedics (307 Hospital of PLA), 100071 Beijing, China.
[Li, Dingfeng] Affiliated Hospital of Academy of Military Medical Sciences, Department of Orthopedics (307 Hospital of PLA), 100071 Beijing, China.
[Zeng, Yanjun] Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
RP Zeng, Y (reprint author), Beijing University of Technology, Biomechanics and Medical Information Institute, 100022 Beijing, China.
EM yjzeng@bjut.edu.cn
CR Yan S, Jichang Z, eds,, 2003)Manual for clinical cancer medicine[M]. People’s Medical Publishing House, Beijing, p 106
Mei W, Xizhi G, 1982, WHO standards for evaluating the cancer treatment effects. Chin J Oncol 4(4):300
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Hong G, Yaling G, 2005, Clinical observation of using Alpha interferon to treat cancerous ulcer. J Clin Oncol 10(4):416–417
Wang YF, Que HF, Xu JN et al, 2012, Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial. Zhong Xi Yi Jie He Xue Bao 10(2):166–175
Wang SQ, Goldberg LH, 2007, Pulsed-dye laser treatment of nonhealing chronic ulcer with hypergranulation tissue. Arch Dermatol 143(6):700–702
Siqi F, Jianxing S, 2010, Free flap transplantation in the treatment of 1 case of huge chronic ulcer induced by breast cancer. Chin J Aesthet Med 19(7):978–979
Guo J, Cui Q, Liu C et al, 2013, Clinical report on transarterial neoadjuvant chemotherapy of malignant fibrous histiocytoma in soft tissue. Clin Transl Oncol 15:370–375
Cheng L, Dingfeng L, Ju Z et al, 2009, Comprehensive treatment of malignant tumor of distal femur based on interventional chemotherapy. Chin J Clin Oncol Rehabil 3(4):250–253
Cui Q, Li DF, Liu C et al, 2011, Two case-reports of the limb salvage treatment of osteosarcoma consolidated with obvious pathological fractures. Pathol Oncol Res 17:973–979
Li D, Cui Q, Liu Yet al, 2011, Chemotherapy response analysis for osteosarcoma with intra-arterial chemotherapy by subcutaneous implantable delivery system. Pathol Oncol Res 17(4):947–953
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 229
EP 234
DI 10.1007/s12253-013-9673-6
PG 6
ER
PT J
AU Kosmaczewska, A
Ciszak, L
Swierkot, J
Szteblich, A
Wiland, P
Frydecka, I
AF Kosmaczewska, Agata
Ciszak, Lidia
Swierkot, Jerzy
Szteblich, Aleksandra
Wiland, Piotr
Frydecka, Irena
TI Alterations in Both the Activatory and Inhibitory Potential of Peripheral Blood CD4+ T Cells in Rheumatoid Arthritis Patients Correlate with Disease Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD28; CD40L; CTLA-4; Rheumatoid arthritis; Disease progression; Therapy
ID CD28; CD40L; CTLA-4; Rheumatoid arthritis; Disease progression; Therapy
AB The chronic nature of rheumatoid arthritis (RA) suggests immune dysfunction, including persistent systemic activation. Therefore, we evaluated the activatory and inhibitory potential as well as proliferative activity of peripheral blood (PB) CD4+ T cells from RA patients in different stages of the disease and after different therapeutic interventions.We found that CD4+ T cells from RA patients were activated in vivo concerning decreased CD28 expression and increase of CD40L, CD69, and CTLA-4 expression; however, the extent of stimulation was suboptimal when compared to healthy controls. Consequently, impaired proliferative activities of these cells were found in all patients irrespective of the active disease duration. Treatment with methotrexate (MTX) and/or inhibitors of TNF-alpha (iTNF) did not significantly influence systemic activation in RA patients, which corresponded with the maintenance of inflammation markers; however, partial restoration of CD28 and CTLA-4 expression as well as clinical improvement were observed. In patients with early disease (the MTX group), we noted higher capacity of CD4+ T cells for restoration of T cell function, whereas cells from the iTNF group with progressive disease remained with a proliferative defect after the treatment. In conclusion, our study demonstrates that the dysregulated expression of molecules interfering with CD4+ Tcell signaling may result in functional impairment of the effector T cells and correlates with disease progression.
C1 [Kosmaczewska, Agata] Polish Academy of Sciences, Institute of Immunology and Experimental TherapyWroclaw, Poland.
[Ciszak, Lidia] Polish Academy of Sciences, Institute of Immunology and Experimental TherapyWroclaw, Poland.
[Swierkot, Jerzy] Wroclaw Medical University, Department of Rheumatology and Internal MedicineWroclaw, Poland.
[Szteblich, Aleksandra] Polish Academy of Sciences, Institute of Immunology and Experimental TherapyWroclaw, Poland.
[Wiland, Piotr] Wroclaw Medical University, Department of Rheumatology and Internal MedicineWroclaw, Poland.
[Frydecka, Irena] Polish Academy of Sciences, Institute of Immunology and Experimental TherapyWroclaw, Poland.
RP Kosmaczewska, A (reprint author), Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Wroclaw, Poland.
EM kosmacz@iitd.pan.wroc.pl
CR Weyand CM, 2000, New insights into the pathogenesis of rheumatoid arthritis. Rheumatology 39:13–18
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Krummel MF, Allison JP, 1995, CD28 and CTLA-4 have opposing effects on the response of Tcells to stimulation. J Exp Med 182:459–465
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 235
EP 243
DI 10.1007/s12253-013-9687-0
PG 9
ER
PT J
AU Wang, BH
Jiang, BZ
Li, M
AF Wang, Bin Hong
Jiang, Biao Zhi
Li, Min
TI Research on the Typical miRNA and Target Genes in Squamous Cell Carcinoma and Adenocarcinoma of Esophagus Cancer with DNA Microarray
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; Differentially expressed miRNA; Target genes interaction network; Function and pathway enrichment analysis
ID Esophageal cancer; Differentially expressed miRNA; Target genes interaction network; Function and pathway enrichment analysis
AB To identify the typically expressed miRNAs in squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of esophagus cancer and their target genes, and explore the related functions and pathways, providing potential biomarkers for esophageal carcinoma diagnosis and treatment. Gene expression profile GSE13937 was downloaded from Gene Expression Omnibus database which includes 152 samples, paired non-cancerous and cancerous, 44 SCC cases and 32 ADC cases; the differentially expressed miRNAs were identified with limma packages in R language after the data were normalized. Selected differentially expressed miRNAs were further analyzed using bioinformatics methods. Firstly, verified targets of miRNAs in two miRNA databases: miRecods and miRTarBase were integrated to select the targets genes of differentially expressed miRNAs. Next, String software was used to construct the target genes interaction network. Finally, function and pathway enrichment analysis of genes in the interaction network was carried out with Gestalt software. Up-regulated hsa-miR-21 and down-regulated hsamiR- 203 were identified by comparing normal and cancer tissue samples, and the targets genes regulated by these two miRNAs were most significantly related to cell cycle function and pathway, especially in the phase of G1/S. The two differentially expressed miRNA: hsa-miR-21 and hsa-miR-203 provide evidence for early diagnosis and treatment of esophageal carcinoma. The functions and pathways of target genes shows that deep understanding of cell cycle G1/S will help to illustrate the relationship between cell cycle regulation and pathogenesis of esophageal cancer.
C1 [Wang, Bin Hong] Fengxian District Central Hospital, Sixth People’s Hospital in Southern Branch, Affiliated to Shanghai Jiao Tong University, Department of Cardiac-Thoracic Surgery, 201499 Shanghai, China.
[Jiang, Biao Zhi] Fengxian District Central Hospital, Sixth People’s Hospital in Southern Branch, Affiliated to Shanghai Jiao Tong University, Department of Cardiac-Thoracic Surgery, 201499 Shanghai, China.
[Li, Min] Fengxian District Central Hospital, Sixth People’s Hospital in Southern Branch, Affiliated to Shanghai Jiao Tong University, Department of Cardiac-Thoracic Surgery, 201499 Shanghai, China.
RP Li, M (reprint author), Fengxian District Central Hospital, Sixth People’s Hospital in Southern Branch, Affiliated to Shanghai Jiao Tong University, Department of Cardiac-Thoracic Surgery, 201499 Shanghai, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 245
EP 252
DI 10.1007/s12253-013-9688-z
PG 8
ER
PT J
AU Kawakita, A
Yanamoto, S
Yamada, Shi
Naruse, T
Takahashi, H
Kawasaki, G
Umeda, M
AF Kawakita, Akiko
Yanamoto, Souichi
Yamada, Shin-ichi
Naruse, Tomofumi
Takahashi, Hidenori
Kawasaki, Goro
Umeda, Masahiro
TI MicroRNA-21 Promotes Oral Cancer Invasion via the Wnt/β-Catenin Pathway by Targeting DKK2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MiR-21; Oral tongue squamous cell carcinoma; DKK2; β-catenin; Tumor invasion
ID MiR-21; Oral tongue squamous cell carcinoma; DKK2; β-catenin; Tumor invasion
AB MicroRNA-21 (miR-21) is overexpressed in a wide variety of cancers and has been related to cellular proliferation, apoptosis, and invasion; however, the function of miR-21 is unknown in oral tongue squamous cell carcinoma (OTSCC). The purpose of this study was to examine miR-21 expression in OTSCC, correlate it with clinicopathological factors, and investigate its contribution to OTSCC cell invasion. MiR-21 expression in 79 primary OTSCCs was evaluated using locked nucleic acid in situ hybridization, and correlation was examined with the clinicopathological factors. To determine the miR-21 target, we searched for molecular genes involved in tumor invasion using the commonly cited prediction program miRanda. In an OTSCC cell line, SCC25 cells, we further evaluated whether miR-21 contributes to cell invasiveness by blocking its expression with a specific knockdown LNA probe and confirmed the direct target by Matrigel invasion assay and Western blotting. MiR-21 overexpression was detected in 60 of 79 cases (75.9 %) and correlated with the pattern of invasion (P =0.016). We selected DKK2 as a Wnt/antagonist involved in tumor invasion. MiR-21 overexpression was significantly correlated with the DKK2-/β-catenin- immunohistochemical phenotype. Knockdown ofmiR-21 significantly decreased the invasion potential of SCC25 cells with up-regulated DKK2. It was found that miR-21 is overexpressed and associated with tumor invasion in OTSCC, and that miR-21 promotes OTSCC cell invasion via the Wnt/β-catenin pathway by targeting DKK2 in vitro. These results suggest that miR-21 may be a potential therapeutic target for OTSCC treatment.
C1 [Kawakita, Akiko] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yamada, Shin-ichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Takahashi, Hidenori] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawasaki, Goro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Yanamoto, S (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM syana@nagasaki-u.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 253
EP 261
DI 10.1007/s12253-013-9689-y
PG 9
ER
PT J
AU Lan, YJ
Chen, H
Chen, JQ
Lei, QH
Zheng, M
Shao, ZR
AF Lan, Yan-Ju
Chen, Huan
Chen, Jia-Qi
Lei, Qiu-Hua
Zheng, Min
Shao, Zhe-Ren
TI Immunolocalization of Vimentin, Keratin 17, Ki-67, Involucrin, β-Catenin and E-Cadherin in Cutaneous Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Squamous cell carcinoma; Epithelial-mesenchymal transition; Immunolocalization
ID Squamous cell carcinoma; Epithelial-mesenchymal transition; Immunolocalization
AB Skin squamous cell carcinoma (SCC) is a subtype of very aggressive skin cancers. To investigate if epithelialmesenchymal transition (EMT), a process for epitheloid cells losing their polarity and cohesiveness and transform into spindle-shaped cells, occurs in skin SCC. By using immunofluorescence, we defined the immunolocalization of vimentin, Keratin 17, β-catenin, E-cadherin, Ki-67 and involucrin, in SCC samples. Our results show reduced activity of involucrin and E-cadherin, and increased expression of Ki-67, β-catenin, Keratin 17 and vimentin in SCC. These data propose that EMT really occurs in poorly differentiated SCC and keratin 17 and involucrin may be another two biomarkers for EMT.
C1 [Lan, Yan-Ju] Lishui Central Hospital, Department of DermatologyLishui, China.
[Chen, Huan] Lishui Central Hospital, Department of DermatologyLishui, China.
[Chen, Jia-Qi] Zhejiang University School of Medicine, Second Affiliated Hospital, Department of DermatologyHangzhou, China.
[Lei, Qiu-Hua] Zhejiang University School of Medicine, Second Affiliated Hospital, Department of DermatologyHangzhou, China.
[Zheng, Min] Zhejiang University School of Medicine, Second Affiliated Hospital, Department of DermatologyHangzhou, China.
[Shao, Zhe-Ren] Zhejiang University School of Medicine, Second Affiliated Hospital, Department of Plastic Surgery, 88 Jiefang Rd, 310009 Hangzhou, China.
RP Shao, ZR (reprint author), Zhejiang University School of Medicine, Second Affiliated Hospital, Department of Plastic Surgery, 310009 Hangzhou, China.
EM shaozju@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 263
EP 266
DI 10.1007/s12253-013-9690-5
PG 4
ER
PT J
AU Orsini, G
Legitimo, A
Failli, A
Ferrari, P
Nicolini, A
Spisni, R
Miccoli, P
Consolini, R
AF Orsini, Giulia
Legitimo, Annalisa
Failli, Alessandra
Ferrari, Paola
Nicolini, Andrea
Spisni, Roberto
Miccoli, Paolo
Consolini, Rita
TI Quantification of Blood Dendritic Cells in Colorectal Cancer Patients During the Course of Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating dendritic cells; Colorectal cancer; Immunosuppression; Flow cytometry
ID Circulating dendritic cells; Colorectal cancer; Immunosuppression; Flow cytometry
AB Colorectal cancer is a malignancy with poor prognosis that might be associated with defective immune function. The aim of the present study was to investigate circulating dendritic cells in colorectal cancer patients, in order to contribute to elucidate tumor-escape mechanisms and to point out a possible correlation with the clinical condition of the disease. Therefore, we enumerated ex vivo myeloid and plasmacytoid dendritic cells, through multicolor flow cytometry, in 26 colorectal patients and 33 healthy controls. Furthermore we performed several analyses at determined time points in order to define the immunological trend of cancer patients after surgery and other conventional treatments. At the preoperative time point the absolute number of plasmacytoid dendritic cells in cancer patients was significantly reduced in comparison to controls, this result being mainly referred to stage III-IV patients. The number of myeloid dendritic cells did not show any significant difference compared to healthy controls; interestingly the expression of the tolerogenic antigen CD85k was significantly higher on cancer patients’ myeloid dendritic cells than controls’. At the following samplings, circulating dendritic cell absolute number did not show any difference compared to controls. Conclusively the impairment of the number of circulating dendritic cells may represent one of the tumor escape mechanisms occurring in colorectal cancer. These alterations seem to be correlated to cancer progression. Our work sheds light on one of dendritic cell-based tumor immune escape mechanisms. This knowledge may be useful to the development of more effective immunotherapeutic strategies.
C1 [Orsini, Giulia] University of Pisa, Department of Experimental and Clinical Medicine, via Roma 67, 56126 Pisa, Italy.
[Legitimo, Annalisa] University of Pisa, Department of Experimental and Clinical Medicine, via Roma 67, 56126 Pisa, Italy.
[Failli, Alessandra] Azienda Ospedaliero-Universitaria PisanaPisa, Italy.
[Ferrari, Paola] University of Pisa, Department of Experimental and Clinical Medicine, via Roma 67, 56126 Pisa, Italy.
[Nicolini, Andrea] University of Pisa, Department of Experimental and Clinical Medicine, via Roma 67, 56126 Pisa, Italy.
[Spisni, Roberto] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical AreaPisa, Italy.
[Miccoli, Paolo] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical AreaPisa, Italy.
[Consolini, Rita] University of Pisa, Department of Experimental and Clinical Medicine, via Roma 67, 56126 Pisa, Italy.
RP Orsini, G (reprint author), University of Pisa, Department of Experimental and Clinical Medicine, 56126 Pisa, Italy.
EM giulia.orsini@for.unipi.it;gl84@hotmail.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 267
EP 276
DI 10.1007/s12253-013-9691-4
PG 10
ER
PT J
AU Theocharis, S
Klijanienko, J
Giaginis, C
Alexandrou, P
Patsouris, E
Sastre-Garau, X
AF Theocharis, Stamatios
Klijanienko, Jerzy
Giaginis, Constantinos
Alexandrou, Paraskevi
Patsouris, Efstratios
Sastre-Garau, Xavier
TI Ephrin Receptor (Eph) -A1, -A2, -A4 and -A7 Expression in Mobile Tongue Squamous Cell Carcinoma: Associations with Clinicopathological Parameters and Patients Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mobile tongue squamous cell carcinoma; Ephrin receptors; Clinicopathological parameters; Prognosis; Immunohistochemistry
ID Mobile tongue squamous cell carcinoma; Ephrin receptors; Clinicopathological parameters; Prognosis; Immunohistochemistry
AB Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of Eph- A1, -A2, -A4 and -A7 protein expression in mobile tongue squamous cell carcinoma (SCC). Eph-A1, -A2, -A4 and -A7 protein expression was assessed immunohistochemically on 37 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients’ survival. All the examined mobile tongue SCC cases were found positive for Eph-A1, -A2, -A4 and -A7. Significant associations were noted between high Eph-A1, -A4 and -A7 expression and absence of lymph node metastases (p=0.0263, p=0.0461 and p=0.0461, respectively). High Eph-A1, -A2 and -A7 expression was significantly more frequently observed in patients presenting absence of vascular invasion (p =0.0444), dense stromal inflammatory reaction (p=0.0063) and female gender (p=0.0327), respectively. Mobile tongue SCC patients with high Eph-A7 expression presented longer overall and disease-free survival compared to those with low Eph-A7 expression (log-rank test, p=0.0093 and p=0.0164, respectively). In multivariate analysis, Eph-A7 expression was identified as independent prognostic factor of overall survival (Coxregression analysis, p=0.0426). The present study supported evidence that Ephs may participate in the malignant transformation of mobile tongue SCC, reinforcing their utility as clinical markers for patients’ management and prognosis, as also as targets for potential therapeutic intervention in tongue chemoprevention.
C1 [Theocharis, Stamatios] Institut Curie, Department of PathologyParis, France.
[Klijanienko, Jerzy] Institut Curie, Department of PathologyParis, France.
[Giaginis, Constantinos] University of Athens, Medical School, Department of Pathology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, Department of Pathology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, Department of Pathology, 75 M. Asias str., Goudi, GR11527 Athens, Greece.
[Sastre-Garau, Xavier] Institut Curie, Department of PathologyParis, France.
RP Theocharis, S (reprint author), Institut Curie, Department of Pathology, Paris, France.
EM theocharis@ath.forthnet.gr
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Kinch MS, Moore MB, Harpole DH, 2003, Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival. Clin Cancer Res 9:613–618
Shao Z, Zhang WF, Chen XM, Shang ZJ, 2008, Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: correlation with the angiogenesis and clinical outcome. Oral Oncol 44:1110–1117
Kamat AA, Coffey D, MerrittWMet al, 2009, EphA2 overexpression is associated with lack of hormone receptor expression and poor outcome in endometrial cancer. Cancer 115:2684–2692
Miyazaki T, Kato H, Fukuchi M, Nakajima M, Kuwano H, 2003, EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma. Int J Cancer 103:657–663
Wang LF, Fokas E, Bieker M et al, 2008, Increased expression of EphA2 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. Oncol Rep 19:151–156
Herrem CJ, Tatsumi T, Olson KS et al, 2005, Expression of EphA2 is prognostic of disease-free interval and overall survival in surgically treated patients with renal cell carcinoma. Clin Cancer Res 11:226–231
Oki M, Yamamoto H, Taniguchi H, Adachi Y, Imai K, Shinomura Y, 2008, Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers. World J Gastroenterol 14:5650–5656
Wang LF, Fokas E, Juricko J et al, 2008, Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer 8:79
Pasquale EB, 2010, Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 10:165–180
Tandon M, Vemula SV, Mittal SK, 2011, Emerging strategies for EphA2 receptor targeting for cancer therapeutics. Expert Opin Ther Targets 15:31–51
Landen CN Jr, Chavez-Reyes A, Bucana C et al, 2005, Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 65:6910–6918
Shahzad MM, Lu C, Lee JW et al, 2009, Dual targeting of EphA2 and FAK in ovarian carcinoma. Cancer Biol Ther 8:1027–1034
Zhuang G, Brantley-Sieders DM, Vaught D et al, 2010, Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res 70:299–308
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 277
EP 284
DI 10.1007/s12253-013-9692-3
PG 8
ER
PT J
AU Li, J
Yang, ZL
Zou, Q
Yuan, Y
Li, J
Liang, L
Zhen, G
Chen, S
AF Li, Jiequn
Yang, Zhu-Lin
Zou, Qiong
Yuan, Yuan
Li, Jinghe
Liang, Lufeng
Zhen, Guixiang
Chen, Senlin
TI Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder: An Immunohistochemistry Study of Prognostic Markers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladdercancer; Adenocarcinoma; Squamous cell carcinoma; Adenosquamous carcinoma; KRT19; hASH1; Prognosis; Metastasis
ID Gallbladdercancer; Adenocarcinoma; Squamous cell carcinoma; Adenosquamous carcinoma; KRT19; hASH1; Prognosis; Metastasis
AB Gallbladder cancers (GBCs) are highly aggressive and lethal diseases. However, the key molecular mechanisms responsible for the progression and prognosis of GBCs have not been identified. No biological markers for effectively identifying GBC subtypes have been reported. In this study the expression of keratin 19 (KRT19) and human achaetescute homolog 1 (hASH1) proteins in 46 squamous cell/ adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry. Negative KRT19 or positive hASH1 expression were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASC patients. In contrast, positive KRT19 and hASH1 expression were significantly associated with large tumor size, lymph metastasis, invasion, and TNM stage in AC patients. Univariate Kaplan–Meier analysis showed that loss of KRT19 or elevated hASH1 expression significantly correlated with decreased survival in SC/ASC patients. In contrast, positive KRT19 and hASH1 expression correlated with a shorter survival time in AC patients. Multivariate Cox regression analysis showed that negative KRT19 expression or positive hASH1 expression was an independent poor-prognostic predictor in SC/ASC, but positive KRT19 and hASH1 expression were poor-prognostic factors in AC patients. Our study suggested that hASH1 can be used to determine the malignancy of SC/ASC and AC tumors and is associated with poor prognosis. In contrast, KRT19 is a protective factor in AC patients but a sign of malignancy in SC/ ASC patients.
C1 [Li, Jiequn] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan, China.
[Yang, Zhu-Lin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Zou, Qiong] Central South University, Third Xiangya Hospital, Department of Pathology, 410013 Changsha, Hunan, China.
[Yuan, Yuan] Central South University, Third Xiangya Hospital, Department of Pathology, 410013 Changsha, Hunan, China.
[Li, Jinghe] Central South University, Xiangya Basic Medical College, Department of Pathology, 410078 Changsha, Hunan, China.
[Liang, Lufeng] Hunan Provincial People’s Hospital, Department of Hepatobiliary and Pancreatic Surgery, 410007 Changsha, Hunan, China.
[Zhen, Guixiang] Loudi Central Hospital, Department of Pathology, 417011 Loudi, Hunan, China.
[Chen, Senlin] Hunan Provincial Tumor Hospital, Department of Pathology, 410013 Changsha, Hunan, China.
RP Yang, ZL (reprint author), Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, China.
EM zhulinyang@yahoo.com
CR Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics, 2008. CA Cancer J Clin 58:71–96
Jayaraman S, Jarnagin WR, 2010, Management of gallbladder cancer. Gastroenterol Clin N Am 39:331–342
Bamburg JR, Wiggan OP, 2002, ADF/cofilin and actin dynamics in disease. Trends Cell Biol 12:598–605
Roa JC, Tapia O, Cakir A et al, 2011, Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas. Mod Pathol 24: 1069–1078
Wang W, Eddy R, Condeelis J, 2007, The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer 7:429–440
Nishihara K, Nagai E, Izumi Y, Yamaguchi K, Tsuneyoshi M, 1994, Adenosquamous carcinoma of the gallbladder: a clinicopathological, immunohistochemical and flow-cytometric study of twenty cases. Jpn J Cancer Res 85:389–399
Kondo M, Dono K, Sakon M et al, 2002, Adenosquamous carcinoma of the gallbladder. Hepato-Gastroenterology 49:1230–1234
Park SB, Kim YH, Rho HL, Chae GB, Hong SK, 2012, Primary carcinosarcoma of the gallbladder. J Korean Surg Soc 82:54–58
Barak V, Goike H, Panaretakis KW, Einarsson R, 2004, Clinical utility of cytokeratins as tumor markers. Clin Biochem 37:529–540
Lacroix M, 2006, Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13: 1033–1067
Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT, 2005, Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57
Chu PG, Weiss LM, 2002, Keratin expression in human tissues and neoplasms. Histopathology 40:403–439
Nozato M, Kaneko S, Nakagawara A, Komuro H, 2013, Epithelialmesenchymal transition-related gene expression as a new prognostic marker for neuroblastoma. Int J Oncol 42:134–140
Jain R, Fischer S, Serra S, Chetty R, 2010, The use of Cytokeratin 19, CK19, immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol 18:9–15
Axelson H, 2004, The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1. Cancer Lett 204:171–178
Ball DW(2004, Achaete-scute homolog-1 and Notch in lung neuroendocrine development and cancer. Cancer Lett 204:159–169
Sippel RS, Carpenter JE, Kunnimalaiyaan M, Chen H, 2003, The role of human achaete-scute homolog-1 in medullary thyroid cancer cells. Surgery 134:866–871
Kunnimalaiyaan M, Traeger K, Chen H, 2005, Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells. Am J Physiol Gastrointest Liver Physiol 289:G636–G642
Shida T, Furuya M, Nikaido T et al, 2005, Aberrant expression of human achaete-scute homologue gene 1 in the gastrointestinal neuroendocrine carcinomas. Clin Cancer Res 11(2 Pt 1):450–458
MikiM, Ball DW, Linnoila RI, 2012, Insights into the achaete-scute homolog-1 gene, hASH1, in normal and neoplastic human lung. Lung Cancer 75:58–65
Jensen-Taubman S, Wang XY, Linnoila RI, 2010, Achaete-scute homologue-1 tapers neuroendocrine cell differentiation in lungs after exposure to naphthalene. Toxicol Sci 117:238–248
Liu DC, Yang ZL, 2011, Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma. Pathol Res Pract 207: 472–478
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 285
EP 292
DI 10.1007/s12253-013-9693-2
PG 8
ER
PT J
AU Shi, B
Wang, X
Han, X
Liu, P
Wei, W
Li, Y
AF Shi, Baomin
Wang, Xiuyan
Han, Xujie
Liu, Pengfei
Wei, Weiwei
Li, Yan
TI Functional Modules Analysis Based on Coexpression Network in Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Co-expression network; Functional modules; Pancreatic ductal adenocarcinoma
ID Co-expression network; Functional modules; Pancreatic ductal adenocarcinoma
AB Pancreatic ductal adenocarcinoma (PDAC) is the most common epithelial, exocrine pancreatic malignancy, accounting formore than 80%of themalignant neoplasms of the pancreas. Although the molecular basis of pancreatic cancer is now better understood than ever before, there remains a long distance from being completely understood. In this study, we identified the differentially expressed genes (DEGs) in PDAC tissue compared with normal tissue and constructed a coexpression network by computing the pairwise correlation coefficient between the DEGs. We applied a statistical approach of MCODE to cluster genes in the coexpression network. Ten functional modules were identified in this network. Our results strongly suggest that dysregulations of immune response, homeostasis and cell adhesion may significantly contribute to the development and progression of PDAC. Results from this study will provide the groundwork for the understanding of PDAC. Future studies are needed to confirm some of the possible interactions suggested by this study.
C1 [Shi, Baomin] Tongji Hospital of Tongji University, Department of General Surgery, 389 xincun road, Putuo district, 200065 Shanghai, China.
[Wang, Xiuyan] Tongji Hospital of Tongji University, Department of UltrasonographyShanghai, China.
[Han, Xujie] Tongji Hospital of Tongji University, Department of General Surgery, 389 xincun road, Putuo district, 200065 Shanghai, China.
[Liu, Pengfei] Tongji Hospital of Tongji University, Department of General Surgery, 389 xincun road, Putuo district, 200065 Shanghai, China.
[Wei, Weiwei] Tongji Hospital of Tongji University, Department of General Surgery, 389 xincun road, Putuo district, 200065 Shanghai, China.
[Li, Yan] Tongji Hospital of Tongji University, Department of General Surgery, 389 xincun road, Putuo district, 200065 Shanghai, China.
RP Shi, B (reprint author), Tongji Hospital of Tongji University, Department of General Surgery, 200065 Shanghai, China.
EM shibaominsbm@hotmail.com
CR Alexakis N, Halloran C, RaratyM, Ghaneh P, Sutton R, Neoptolemos JP, 2004, Current standards of surgery for pancreatic cancer. Br J Surg 91(11):1410–1427., DOI 10.1002/bjs.4794
Siegel R,Ward E, Brawley O, Jemal A, 2011, Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61(4):212–236
Ghaneh P, Costello E, Neoptolemos JP, 2007, Biology and management of pancreatic cancer. Gut 56(8):1134–1152
Li D, Xie K, Wolff R, Abbruzzese JL, 2004, Pancreatic cancer. Lancet 363(9414):1049–1057., DOI 10.1016/S0140-6736(04)15841-8
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW, 2008, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321(5897):1801–1806
Carter H, Samayoa J, Hruban RH, Karchin R, 2010, Prioritization of driver mutations in pancreatic cancer using cancer-specific highthroughput annotation of somatic mutations, CHASM). Cancer Biol Ther 10(6):582–587
Zhang G, Schetter A, He P, Funamizu N, Gaedcke J, Ghadimi BM, Ried T, Hassan R, Yfantis HG, Lee DH, Lacy C, Maitra A, Hanna N, Alexander HR, Hussain SP, 2012, DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts clinical outcome in pancreatic ductal adenocarcinoma. PLoS One 7(2):e31507., DOI 10. 1371/journal.pone.0031507
Perez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grutzmann R, Aust D, Rummele P, Knosel T, Herd C, Stemple DL, Kettleborough R, Brosnan JA, Morgan R, Knight S, Yu J, Stegeman S, Collier LS, ten Hoeve JJ, de Ridder J, Klein AP, GogginsM, Hruban RH, Chang DK, Biankin AV, Grimmond SM,Wessels LF,Wood SA, Iacobuzio-Donahue CA, Pilarsky C, Largaespada DA, Adams DJ, Tuveson DA, 2012, The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature 486(7402):266–270., DOI 10.1038/nature11114
VincentA,Omura N, Hong SM, Jaffe A, Eshleman J, GogginsM(2011, Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clin Cancer Res 17(13):4341–4354., DOI 10.1158/1078-0432.CCR-10-3431
Badea L, HerleaV, Dima SO,Dumitrascu T, Popescu I, 2008, Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology 55(88):2016–2027
Badea L, Herlea V, Dima SO, Dumitrascu T, Popescu I, 2008, Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology 55(88): 2015–2026
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 293
EP 299
DI 10.1007/s12253-013-9694-1
PG 7
ER
PT J
AU Manoochehri, M
Karbasi, A
Bandehpour, M
Kazemi, B
AF Manoochehri, Mehdi
Karbasi, Ashraf
Bandehpour, Mojgan
Kazemi, Bahram
TI Down-Regulation of BAX Gene During Carcinogenesis and Acquisition of Resistance to 5-FU in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Carcinogenesis; 5-FU; Chemoresistance; Apoptosis
ID Colorectal cancer; Carcinogenesis; 5-FU; Chemoresistance; Apoptosis
AB Carcinogenesis and resistance to chemotherapy could be as results of expression variations in apoptosis regulating genes. Changes in the expression of apoptosis interfering genes may contribute to colorectal carcinogenesis and resistance to 5-Flourouracil (5-FU) during treatment schedule period. The present study aimed to evaluate the expression of pro-apoptotic and anti-apoptotic genes in colorectal cancer tumor tissues, normal adjacent tissues, and tumor colorectal cancer cell line during acquiring resistance to 5-FU in HT-29 based on Bolus treatment protocol. The normal and tumor tissues were obtained from hospital after surgery and total RNA was extracted for expression analysis. The HT-29 colorectal cancer cell line was cultured and exposed with 5-FU in three stages based on Bolus protocol. The MTT assay and Real Time PCR were carried out to determine the sensitivity to the drug and expression of desired genes, respectively. The obtained data showed that Proapoptotic genes, BAX and BID, were down-regulated in resistant derivate cells compared to wild type HT-29 cells. On the other hand Antiapoptotic genes, CIAP1 and XIAP, showed upregulation in resistant cells compared to wild type ones. Furthermore, BAX and FAS genes showed down-regulation in tumor samples in comparison to normal adjacent tissues. In conclusion, the results of our study suggest that BAX down-regulation could contribute as an important factor during both colorectal carcinogenesis and cell resistance to 5-FU.
C1 [Manoochehri, Mehdi] Shahid Beheshti University of Medical Sciences, Cellular and Molecular Biology Research CenterTehran, Iran.
[Karbasi, Ashraf] Baqyiatallah Research Center for Gastroenterology and Liver Diseases, Gastroenterology and Hepatology DepartmentTehran, Iran.
[Bandehpour, Mojgan] Shahid Beheshti University of Medical Sciences, Cellular and Molecular Biology Research CenterTehran, Iran.
[Kazemi, Bahram] Shahid Beheshti University of Medical Sciences, Cellular and Molecular Biology Research CenterTehran, Iran.
RP Kazemi, B (reprint author), Shahid Beheshti University of Medical Sciences, Cellular and Molecular Biology Research Center, Tehran, Iran.
EM kazemi@sbmu.ac.ir
CR Herszenyi L, Tulassay Z, 2010, Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci 14(4):249–258
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ShaibW, Lee V, Saif MW, 2009, Bolus 5-fluorouracil as an alternative modality to infusion 5-fluorouracil in a patient with rectal cancer and capecitabine-induced cardiotoxicity. In Vivo 23(5):821–826
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Peters GJ, Backus HH, Freemantle S, van Triest B, Codacci-Pisanelli G, van derWilt CL, Smid K, Lunec J, Calvert AH, Marsh S,McLeod HL, Bloemena E, Meijer S, Jansen G, van Groeningen CJ, Pinedo HM, 2002, Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta 1587(2–3):194–205
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 301
EP 307
DI 10.1007/s12253-013-9695-0
PG 7
ER
PT J
AU Dong-Feng, Z
Ting, L
Yong, Z
Cheng, Ch
Xi, Z
Pei-Yan, K
AF Dong-Feng, Zeng
Ting, Liu
Yong, Zhang
Cheng, Chang
Xi, Zhang
Pei-Yan, Kong
TI The TPO/c-MPL Pathway in the Bone Marrow may Protect Leukemia Cells from Chemotherapy in AML Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thrombopoietin; c-MPL; Acutemyeloid leukemia; Chemotherapy resistance; Relapse
ID Thrombopoietin; c-MPL; Acutemyeloid leukemia; Chemotherapy resistance; Relapse
AB Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle–dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn’t been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P <0.05). The osteoblasts derived from AML patients’ BMSCs secreted more TPO than the osteoblasts derived from normal control BMSCs (P <0.05). A strong positive correlation between the TPO level and c-MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblastswas the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patientderived blasts and leukemia repopulating cells need to be further studied.
C1 [Dong-Feng, Zeng] Third Military Medical University, Xinqiao Hospital, Department of Hematology, 400037 Chongqing, China.
[Ting, Liu] Third Military Medical University, Daping Hospital, Department of Ophtalmology, 400042 Chongqing, China.
[Yong, Zhang] Chengdu General Hospital of Chengdu Military Region, Department of Hematology, 610000 Chengdu, China.
[Cheng, Chang] Third Military Medical University, Xinqiao Hospital, Department of Hematology, 400037 Chongqing, China.
[Xi, Zhang] Third Military Medical University, Xinqiao Hospital, Department of Hematology, 400037 Chongqing, China.
[Pei-Yan, Kong] Third Military Medical University, Xinqiao Hospital, Department of Hematology, 400037 Chongqing, China.
RP Pei-Yan, K (reprint author), Third Military Medical University, Xinqiao Hospital, Department of Hematology, 400037 Chongqing, China.
EM kongpeiyanpp1312@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 309
EP 317
DI 10.1007/s12253-013-9696-z
PG 9
ER
PT J
AU Mozes, P
Szanto, E
Tiszlavicz, L
Barzo, P
Cserhati, A
Fodor, E
Hideghety, K
AF Mozes, Petra
Szanto, Erika
Tiszlavicz, Laszlo
Barzo, Pal
Cserhati, Adrienne
Fodor, Emese
Hideghety, Katalin
TI Clinical Course of Central Neurocytoma with Malignant Transformation—An Indication for Craniospinal Irradiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Central neurocytoma; Craniospinal dissemination; Radiotherapy; MIB-1 labeling index
ID Central neurocytoma; Craniospinal dissemination; Radiotherapy; MIB-1 labeling index
AB Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25–30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.
C1 [Mozes, Petra] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., 6720 Szeged, Hungary.
[Szanto, Erika] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., 6720 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, Allomas u. 2., 6720 Szeged, Hungary.
[Barzo, Pal] University of Szeged, Department of Neurosurgery, Semmelweis u. 6., 6720 Szeged, Hungary.
[Cserhati, Adrienne] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., 6720 Szeged, Hungary.
[Fodor, Emese] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., 6720 Szeged, Hungary.
[Hideghety, Katalin] University of Szeged, Department of Oncotherapy, Koranyi fasor 12., 6720 Szeged, Hungary.
RP Mozes, P (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM mozespetra@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 319
EP 325
DI 10.1007/s12253-013-9697-y
PG 7
ER
PT J
AU Horvath, K
Pete, I
Vereczkey, I
Dudnyikova, A
Godeny, M
AF Horvath, Katalin
Pete, Imre
Vereczkey, Ildiko
Dudnyikova, Anna
Godeny, Maria
TI Evaluation of the Accuracy of Preoperative MRI in Measuring Myometrial Infiltration in Endometrial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MRI; Endometriumcarcinoma; Myometrial infiltration; Benign uterine lesions
ID MRI; Endometriumcarcinoma; Myometrial infiltration; Benign uterine lesions
AB The aim of our study was to evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the pretreatment evaluation of myometrium invasion in endometrial cancer. Our retrospective study concerns 89 patients with endometrial cancer, who had preoperative MR evaluation of myometrium invasion and we compared it with histological results. Considering histological type and grade, we had excluded patients with poor prognosis, and separately evaluated those cases where the depth of myometrium invasion is the main prognostic factor determining the choice treatment. Of the 89 cases MRI had accurately evaluated the depth of myometrial invasion in 75 patients. Based on data from all cases, we found the sensitivity of detection of deep myometrial infiltration by MRI (Sv) 71 %, specificity (Sp) 92 %, accuracy (Acc) 84 %, positive predictive value (PPV) 86 % and negative predictive value (NPV) 83 %. Excluding patients with poor prognosis according to histology and grade, these data were Sv 71 %, Sp 95 %, Acc 87 %, PPV 90 %, NPV 84 %. In conclusion, MRI is an efficient diagnostic tool in assessing myometrial infiltration, which is necessary for proper preoperative staging and therapy planning, including evaluation of the necessity of lymphadenectomy. Certain factors may interfere with evaluation of MRI results, thus hindering the precise determination of the level of myometrial infiltration.
C1 [Horvath, Katalin] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Pete, Imre] National Institute of Oncology, Center of GynaecologyBudapest, Hungary.
[Vereczkey, Ildiko] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Dudnyikova, Anna] National Institute of Oncology, Center of GynaecologyBudapest, Hungary.
[Godeny, Maria] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
RP Horvath, K (reprint author), National Institute of Oncology, Center of Radiology, Budapest, Hungary.
EM vakhor2@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 327
EP 333
DI 10.1007/s12253-013-9699-9
PG 7
ER
PT J
AU Yu, Y
Huang, T
Wu, Y
Ma, X
Yu, G
Qi, J
AF Yu, Yongjiang
Huang, Tao
Wu, Yu
Ma, Xiaorong
Yu, Guopeng
Qi, Jun
TI In-Vitro and In-Vivo Imaging of Prostate Tumor Using NaYF4: Yb, Er Up-Converting Nanoparticles
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NaYF4:Yb; Er; Nanoparticles; Prostate tumor cells; Biological imaging
ID NaYF4:Yb; Er; Nanoparticles; Prostate tumor cells; Biological imaging
AB The aim of this study was to investigate the feasibility of prostate tumor bioimaging both in vitro and in vivo using an upconversion fluorophore, NaYF4: Yb, Er nanoparticles. Luminescent signals of human prostate cancer cells (CWR22R and LNCaP) labeled with NaYF4: Yb, Er nanoparticles were detected by laser scanning confocal microscope, while Cy3 or FITC was used as control probe. Mouse-human prostate cancer model was developed by subcutaneously injecting the CWR22R cells into BALB/c nude mice to investigate the in-vivo imaging properties of NaYF4:Yb, Er nanoparticles. Both CWR22R and LNCaP cells could phagocytose NaYF4:Yb, Er nanoparticles in vitro, and the cellular uptake of CWR22R cells was much higher than that of LNCaP cells (95.42±3.47% vs. 51.63±6.43 %), which made us choose the former for the further study. CWR22R cells pre-labeled with NaYF4:Yb, Er nanoparticles showed no obvious decrease of fluorescence intensity (P >0.05) after light exposure, while the fluorescence intensity of Cy3 or FITC labeled cells decreased rapidly with prolonged bleaching (P <0.05). Furthermore, the in-vivo results showed that the prostate cancer cells pre-labeled with or without NaYF4:Yb, Er nanoparticles formed tumors 4 weeks after injection, and the tumor length-diameter of the nanoparticle group and the control group was (10.3±2.0) mm and (9.8±2.5) mm, respectively. Significant upconversion fluorescence signals were observed in the tumors of the nanoparticle group when being excited at 980 nmby a NIR laser. In summary, the results suggest that as an intensive fluorescence imaging label agent, NaYF4:Yb, Er nanoparticles possess unique features and can be used for imaging prostate tumor cells both in vitro and in vivo by phagocytosis.
C1 [Yu, Yongjiang] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, No.1665 Kongjiang Road, Yangpu District, 200092 Shanghai, China.
[Huang, Tao] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, No.1665 Kongjiang Road, Yangpu District, 200092 Shanghai, China.
[Wu, Yu] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, No.1665 Kongjiang Road, Yangpu District, 200092 Shanghai, China.
[Ma, Xiaorong] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Plastic Surgery, 200092 Shanghai, China.
[Yu, Guopeng] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, No.1665 Kongjiang Road, Yangpu District, 200092 Shanghai, China.
[Qi, Jun] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, No.1665 Kongjiang Road, Yangpu District, 200092 Shanghai, China.
RP Qi, J (reprint author), Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of Urology, 200092 Shanghai, China.
EM jasonqi@sh163.net
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 335
EP 341
DI 10.1007/s12253-013-9700-7
PG 7
ER
PT J
AU Wang, Sh
Lu, Sh
Geng, Sh
Ma, Sh
Liang, Z
Jiao, B
AF Wang, Shuai
Lu, Shengkui
Geng, Shaomei
Ma, Shucheng
Liang, Zhaohui
Jiao, Baohua
TI Decreased expression of microRNA-206 correlates with poor clinical outcome in patients with malignant astrocytomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNA-206; Astrocytoma; Expression; Prognosis
ID microRNA-206; Astrocytoma; Expression; Prognosis
AB MicroRNA-206 (miR-206) has been proved to function as a tumor suppressor in several types of human malignant cancers. More recently, it has been demonstrated that the ectopic expression of miR-206 significantly inhibited the proliferation and promoted apoptosis at the early stages in glioma cell U343. In order to investigate the clinical significance of miR-206 expression in human astrocytoma, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-206 in 108 astrocytoma and 20 normal brain tissues. As the results, the expression levels of miR-206 in astrocytoma tissues were significantly lower than those in normal brain tissues (P <0.001). Additionally, the decreased expression of miR-206 in astrocytoma was significantly associated with advanced pathological grade (P =0.008), low Karnofsky performance score (KPS, P =0.02), and large tumor size (P=0.01). Moreover, Kaplan-Meier survival and Cox regression analyses showed that low miR-206 expression (P <0.001) and advanced pathological grade (P =0.02) were independent factors predicting poor prognosis for astrocytomas. In conclusion, this is the first report of the differential expression of miR-206 in human astrocytoma tissues. MiR-206 could be a valuable marker of astrocytoma progression and low miR-206 expression is associated with poor overall survival in patients with malignant astrocytomas.
C1 [Wang, Shuai] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
[Lu, Shengkui] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
[Geng, Shaomei] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
[Ma, Shucheng] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
[Liang, Zhaohui] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
[Jiao, Baohua] Second Hospital of Hebei Medical University, Department of Neurosurgery, No. 215, Hepingxi Road, 050000 Shijiazhuang, Hebei Province, China.
RP Jiao, B (reprint author), Second Hospital of Hebei Medical University, Department of Neurosurgery, 050000 Shijiazhuang, China.
EM jbhhbey@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 343
EP 348
DI 10.1007/s12253-013-9701-6
PG 6
ER
PT J
AU Liu, Y
Song, J
Li, Y
Zhao, Y
Ju, Q
Zhou, G
Li, G
AF Liu, Yanhong
Song, Jie
Li, Yuehui
Zhao, Yanjie
Ju, Qiang
Zhou, Guohua
Li, Guancheng
TI Monoclonal Antibody Preparation and Expression Profile Analysis of a Novel Hepatoma Associated Gene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Hepatoma associated gene; Monoclonal antibody; Immunohistochemistry; Expression profile
ID Hepatocellular carcinoma; Hepatoma associated gene; Monoclonal antibody; Immunohistochemistry; Expression profile
AB Hepatoma associated gene (HTA), a gene screened and cloned by our previous research, was specifically expressed in certain kinds of tumors and had a cancer-promoting role in hepatocellular carcinoma (HCC). To further elucidate the mechanism of HTA in hepatoma carcinogenesis and its potential role as a cancer biomarker, refolded HTA protein (HTA) was obtained by prokaryotic recombinant expression system and immobilized metal affinity chromatography. Then anti-HTA monoclonal antibody (mAb) was produced by hybridoma technique. Using the high titer anti-HTA mAb with high specificity obtained, the expression profile of HTA was analysed by immunohistochemistry staining. It showed that HTA expressed specifically in some kinds of tumors, and didn’t express in almost any of the normal tissues. The positive expression rate and expression quantity of HTA was significantly higher in HCC tissues than in hepatic cirrhosis tissues, hepatic fibrosis tissues and normal hepatic tissues. The expression of HTA was positively correlated with hepatoma carcinogenic process.
C1 [Liu, Yanhong] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Song, Jie] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Li, Yuehui] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Zhao, Yanjie] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Ju, Qiang] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Zhou, Guohua] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
[Li, Guancheng] Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, Hunan, China.
RP Li, G (reprint author), Key Laboratory of Carcinogenesis Ministry of Health, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, 410078 Changsha, China.
EM libsun@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 349
EP 356
DI 10.1007/s12253-013-9703-4
PG 8
ER
PT J
AU Hunyadi, J
Andras, Cs
Szabo, I
Szanto, J
Szluha, K
Sipka, S
Kovacs, P
Kiss, A
Szegedi, Gy
Altorjay, I
Sapy, P
Antal-Szalmas, P
Toth, L
Fazekas, Gy
Rajnavolgyi,
AF Hunyadi, Janos
Andras, Csilla
Szabo, Imre
Szanto, Janos
Szluha, Kornelia
Sipka, Sandor
Kovacs, Peter
Kiss, Attila
Szegedi, Gyula
Altorjay, Istvan
Sapy, Peter
Antal-Szalmas, Peter
Toth, Laszlo
Fazekas, Gyorgy
Rajnavolgyi, Eva
TI Autologous Dendritic Cell Based Adoptive Immunotherapy of Patients with Colorectal Cancer—A Phase I-II Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dendritic cell; Vaccination; Colorectal cancer; Autologous
ID Dendritic cell; Vaccination; Colorectal cancer; Autologous
AB Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4+ and CD8+ Tlymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient’s immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeuticmodality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.
C1 [Hunyadi, Janos] University of Debrecen, Medical and Health Science Center, Clinical Centre for Cell Therapy, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Andras, Csilla] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
[Szabo, Imre] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
[Szanto, Janos] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
[Szluha, Kornelia] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
[Sipka, Sandor] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Kovacs, Peter] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Kiss, Attila] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Szegedi, Gyula] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Altorjay, Istvan] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Sapy, Peter] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
[Antal-Szalmas, Peter] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Fazekas, Gyorgy] University of Debrecen, Medical and Health Science Center, Clinical Centre for Cell Therapy, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Rajnavolgyi, Eva] University of Debrecen, Faculty of Medicine, Division of Clinical ImmunologyDebrecen, Hungary.
RP Szabo, I (reprint author), University of Debrecen, Department of Oncology, 4012 Debrecen, Hungary.
EM szabo.imre@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 357
EP 365
DI 10.1007/s12253-013-9704-3
PG 9
ER
PT J
AU Valibeigi, B
Amirghofran, Z
Golmoghaddam, H
Hajihosseini, R
Kamazani, MF
AF Valibeigi, Behnaz
Amirghofran, Zahra
Golmoghaddam, Hossein
Hajihosseini, Reza
Kamazani, M Fatemeh
TI Fas Gene Variants in Childhood Acute Lymphoblastic Leukemia and Association with Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute lymphoblastic leukemia; Fas; Polymorphism
ID Acute lymphoblastic leukemia; Fas; Polymorphism
AB Fas molecule is one of the main important molecules involved in apoptotic cell death. Single nucleotide polymorphisms in the promoter of Fas gene at positions −1377G/A and −670 A/G may affect its expression and play an important role in the pathology of leukemia. In the present study the association between these polymorphisms and risk of the development of acute lymphoblastic leukemia (ALL) in children with ALL compared to cancer-free control subjects was examined by polymerase chain reaction- based restriction fragment length polymorphism. The relationship between the polymorphisms and clinical and laboratory features of the patients and response to therapy were determined. No significant differences in genotype and allele frequencies between the patients and the control subjects at positions −670 and −1377 were detected. Evaluation of the prognostic factors revealed an association between the GG genotype at position −670 and liver involvement in ALL patients (p < 0.04). Although patients with −1377 AA genotype showed shorter mean complete remission duration, the result of survival analysis did not reach to be significant. In conclusion, results of this study showed no contribution of Fas genotypes at positions −670 and −1377 to risk of ALL in children. The association of Fas GG genotype at position −670 with liver involvement in the patients may show its important role in prognosis of ALL.
C1 [Valibeigi, Behnaz] Payame Noor University, Tehran CenterTehran, Iran.
[Amirghofran, Zahra] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Golmoghaddam, Hossein] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
[Hajihosseini, Reza] Payame Noor University, Tehran CenterTehran, Iran.
[Kamazani, M Fatemeh] Medical School, Shiraz University of Medical Sciences, Department of ImmunologyShiraz, Iran.
RP Amirghofran, Z (reprint author), Medical School, Shiraz University of Medical Sciences, Department of Immunology, Shiraz, Iran.
EM amirghz@sums.ac.ir
CR Daneshbod Y, Amirghofran Z, Tabei SZ, 2005, Bcl-2 expression in acute myelogenous leukemia: the relation to myeloid antigen expression and response to therapy in Iranian patients. Neoplasma 52:109–114
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Sunter NJ, Scott K, Hills R et al, 2012, A functional variant in the core promoter of the CD95 cell death receptor gene predicts prognosis in acute promyelocytic leukemia. Blood 5:196–205
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 367
EP 374
DI 10.1007/s12253-013-9705-2
PG 8
ER
PT J
AU Cai, T
Xiao, J
Wang, Zf
Liu, Q
Wu, H
Qiu, Yz
AF Cai, Tao
Xiao, Jie
Wang, Zhi-fei
Liu, Qiang
Wu, Hao
Qiu, Yuan-zheng
TI Identification of Differentially Coexpressed Genes in Gonadotrope Tumors and Normal Pituitary Using Bioinformatics Methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gene; Gonadotrope tumors; Pituitary; Bioinformatics
ID Gene; Gonadotrope tumors; Pituitary; Bioinformatics
AB To investigate the underlying molecular mechanisms of pituitary tumor by using the microarray expression profiles of pituitary tumor and normal tissue samples. The gene expression profile of GSE26966 was downloaded from Gene Expression Omnibus, including nine normal samples and 14 pituitary tumor samples. The differentially coexpressed genes (DEGs) were identified by Affy package in R Software. The functional and pathway enrichment analysis of the screened DEGs were performed by DAVID. Then, differential coexpression networks were contructed and further analyzed. Functional and pathway enrichment analysis of the 1220 identified DEGs revealed that phosphatidylinositol signaling system, p53 signaling pathway and inositol phosphate metabolism were disturbed in pituitary tumors. The degree of DLK1, CDKN2A and ITGA4 in the constructed differential coexpression network was 46, 45 and 44, respectively. In addition, MPP2 and ASAP2 were the obvious hub genes in the constructed differential coexpression network. Through exploring genes in the differential coexpression networks, the results suggested that DLK1, CDKN2A, ITGA4, MPP2 and ASAP2 may potentially be used as biomarkers for pituitary tumor.
C1 [Cai, Tao] The First Xiangya Hospital of Central South University, Department of OtolaryngologyChangsha, Hunan Province, China.
[Xiao, Jie] The Third Xiangya Hospital of Central South University, Department of EmergencyChangsha, Hunan Province, China.
[Wang, Zhi-fei] The Third Xiangya Hospital of Central South University, Department of NeurosurgeryChangsha, Hunan Province, China.
[Liu, Qiang] The Third Xiangya Hospital of Central South University, Department of NeurosurgeryChangsha, Hunan Province, China.
[Wu, Hao] The Third Xiangya Hospital of Central South University, Department of NeurosurgeryChangsha, Hunan Province, China.
[Qiu, Yuan-zheng] The First Xiangya Hospital of Central South University, Department of OtolaryngologyChangsha, Hunan Province, China.
RP Qiu, Yz (reprint author), The First Xiangya Hospital of Central South University, Department of Otolaryngology, Changsha, China.
EM songyechun@hotmail.com
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Alexander JM, BillerBM, BikkalH, Zervas NT, Arnold A, Klibanski A, 1990, Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 86(1):336–340., DOI 10.1172/JCI114705
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 375
EP 380
DI 10.1007/s12253-013-9706-1
PG 6
ER
PT J
AU Zhang, X
Nie, Y
Li, X
Wu, G
Huang, Q
Cao, J
Du, Y
Li, J
Deng, R
Huang, D
Chen, B
Li, Sh
Wei, B
AF Zhang, Xiangyang
Nie, Yuqiang
Li, Xiaorong
Wu, Guifu
Huang, Qun
Cao, Jie
Du, Yanlei
Li, Junda
Deng, Ruoyu
Huang, Dongshen
Chen, Baozhi
Li, Shang
Wei, Baojun
TI MicroRNA-181a Functions as an Oncomir in Gastric Cancer by Targeting the Tumour Suppressor Gene ATM
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-181a; micro-RNA; Gastric cancer; Target gene; ATM
ID miR-181a; micro-RNA; Gastric cancer; Target gene; ATM
AB Based on our previous experiments, this study is to further investigate the functional significance of miR-181a and its target gene in gastric cancer. Expression of miR-181a was detected by qRT-PCR in three normal gastric tissues and three human gastric cancer cell lines (SGC-7901, MGC-803, and BGC-823 cells). After transfection with miR-181a inhibitor, proliferation, apoptosis, migration, and invasion of the SGC-7901 cells were evaluated. Ataxia-telangiectasia mutation (ATM) was predicted as a target gene of miR-181a with bioinformatics analysis, and was verified by lucifersae reporter assay. Expression of ATM protein in HEK293T cells and tissues was measured by Western Blot. Expression of ATM mRNA in HEK293T cells was measured by RT-PCR. Compared with three non-tumour tissues, the expression of miR-181a in three gastric cancer cells was significantly increased by 26.68, 14.83 and 14.96 folds; Compared with Negative Control(NC) and blank groups, transfection of miR- 181a inhibitor led to inhibition of SGC7901 cell proliferation, invasion, and migration as well as promotion of apoptosis. A luciferase reporter assay demonstrated that ATM was a direct target of miR-181a, miR-181a mimics transfection down regulated ATM mRNA and protein expression. There was inverse correlation between miR-181a and ATM protein expression in gastric cancer and normal gastric tissues. Our study demonstrates that over-expression of miR-181a might be involved in development of gastric cancer by promoting proliferation and inhibiting apoptosis probably through directly targeting ATM. miR-181a modulation may be a potential strategy for the development of miRNA-based therapy of gastric cancer.
C1 [Zhang, Xiangyang] Shenzhen Futian Hospital of TCM, Department of Gastroenterology, No. 6001 North Central Avenue of Futian, 518034 Shenzhen, China.
[Nie, Yuqiang] Guangzhou Medical University, Guangzhou First Municipal People’s Hospital, Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, No.1 Panfu Road, 510180 Guangzhou, China.
[Li, Xiaorong] Shenzhen Futian Hospital of TCM, Department of Gastroenterology, No. 3025 Middle Shennan Road, 518033 Shenzhen, China.
[Wu, Guifu] Shenzhen Futian Hospital of TCM, Department of Gastroenterology, No. 3025 Middle Shennan Road, 518033 Shenzhen, China.
[Huang, Qun] Shenzhen Futian Hospital of TCM, Department of Gastroenterology, No. 3025 Middle Shennan Road, 518033 Shenzhen, China.
[Cao, Jie] Guangzhou Medical University, Guangzhou First Municipal People’s Hospital, Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, No.1 Panfu Road, 510180 Guangzhou, China.
[Du, Yanlei] Guangzhou Medical University, Guangzhou First Municipal People’s Hospital, Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, No.1 Panfu Road, 510180 Guangzhou, China.
[Li, Junda] People’s Hospital Of New District Longhua Shenzhen, Department of Gastroenterology, Jianshe East Road of Longhua New City, 518019 Shenzhen, China.
[Deng, Ruoyu] People’s Hospital Of New District Longhua Shenzhen, Department of Gastroenterology, Jianshe East Road of Longhua New City, 518019 Shenzhen, China.
[Huang, Dongshen] Guangzhou Chest Hospital, 510180 Guangzhou, China.
[Chen, Baozhi] Lanzhou University Second Hospital, 730046 Lanzhou, China.
[Li, Shang] Jiuquan City Health School, 735000 Lanzhou, China.
[Wei, Baojun] People’s Hospital of Gansu Province, 730060 Lanzhou, China.
RP Nie, Y (reprint author), Guangzhou Medical University, Guangzhou First Municipal People’s Hospital, Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, 510180 Guangzhou, China.
EM yuqiangnie@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 381
EP 389
DI 10.1007/s12253-013-9707-0
PG 9
ER
PT J
AU Voros, A
Csorgo, E
Kovari, B
Lazar, P
Kelemen, Gy
Cserni, G
AF Voros, Andras
Csorgo, Erika
Kovari, Bence
Lazar, Peter
Kelemen, Gyongyi
Cserni, Gabor
TI The Use of Digital Images Improves Reproducibility of the Ki-67 Labeling Index as a Proliferation Marker in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Core-biopsy; Ki-67; Proliferation marker; Reproducibility; Digital assessment
ID Breast cancer; Core-biopsy; Ki-67; Proliferation marker; Reproducibility; Digital assessment
AB The proportion of Ki-67 immunostained cells (Ki- 67 labeling index, LI) is one of the most commonly used histology methods for estimating proliferation of breast carcinomas. Although the Ki-67 LI is used in treatment decision making, its reproducibility shows variation in different studies, and is generally less then optimal. The aim of the present study was to investigate how the use of a standardized, partially digitalized counting method could affect reproducibility of determining the Ki-67 LI. Thirty breast cancer core-biopsy samples were stained with B-56, SP-6 and MIB-1 monoclonal Ki-67 antibodies. Each sample was represented by a single digital photograph taken with a x20 objective. Four investigators determined the Ki-67 LI on these digital images by estimation, then by counting with the help of a grid overlaid on the same images. Altogether 720 evaluations were made by 4 independent pathologists. Good to excellent correlation was found between estimations and calculations of each observer. Kappa values >0.6 suggest substantial inter-observer agreement when classifying the cases into a 15 % and 30 % cut-off determined three-tiered or a 4-quarter-based four-tiered categorization, which is better than the fair reproducibility gained on the real slides in a previous study. The results also suggest that the type of the antibody may also impact on the consistency of both estimating and calculating the Ki-67 LIs. The results indicate that counting on digital images may significantly improve reproducibility of determining the KI-67 LI. Interestingly, estimation on the same images is not worse, but is obviously faster and more convenient.
C1 [Voros, Andras] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Csorgo, Erika] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Kovari, Bence] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Lazar, Peter] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
RP Voros, A (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM andrasvoros@libero.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 391
EP 397
DI 10.1007/s12253-013-9708-z
PG 7
ER
PT J
AU Li, N
Abe, Sh
Kurata, M
Abe-Suzuki, Sh
Onishi, I
Kirimura, S
Murayama, T
Hidaka, M
Kawano, F
Kitagawa, M
AF Li, Na
Abe, Shinya
Kurata, Morito
Abe-Suzuki, Shiho
Onishi, Iichiroh
Kirimura, Susumu
Murayama, Toshihiko
Hidaka, Michihiro
Kawano, Fumio
Kitagawa, Masanobu
TI Over-Expression of Cancerous Inhibitor of PP2A (CIP2A) in Bone Marrow Cells from Patients with a Group of High-Risk Myelodysplastic Syndromes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CIP2A; c-MYC; Myelodysplastic syndromes; Bone marrow; Immunohistochemistry
ID CIP2A; c-MYC; Myelodysplastic syndromes; Bone marrow; Immunohistochemistry
AB Cancerous inhibitor of PP2A (protein phosphatase 2A) (CIP2A) is an inhibitor of PP2A, a phosphatase and tumor suppressor that regulates cell proliferation, differentiation, and survival. The aim of this study was to investigate whether CIP2A plays a role in the progression of myelodysplastic syndromes (MDS). Immunohistochemical analysis revealed that a fraction patients having refractory anemia with excess blasts (RAEB)-1 (4 out of 12) and RAEB-2 (10 out of 14) exhibited significant expression of CIP2A in bone marrow hematopoietic cells, while all patients with refractory cytopenia with unilineage or multilineage dysplasia (RCUD/ RCMD) (0 out of 18) and the control group (0 out of 17) were negative. CIP2A was mainly expressed by the MPO-positive myeloid series of cells and partly by the CD34-positive cells in association with the expression of phosphorylated c-MYC (pc- MYC) protein and the cell cycle-related proteins Ki-67, MCM2, and geminin. The percentage of p-c-MYC-positive cells in the bone marrow of CIP2A-positive MDS cases was significantly higher than that in CIP2A-negative MDS cases (P <0.01). The expression levels of mRNA for CIP2A and PP2A exhibited positive correlation in MDS/control bone marrow. These results suggest that up-regulated expression of CIP2A might play a role in the proliferation of blasts in the MDS bone marrow and in disease progression in at least some cases.
C1 [Li, Na] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Abe, Shinya] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Kurata, Morito] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Abe-Suzuki, Shiho] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Onishi, Iichiroh] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Kirimura, Susumu] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
[Murayama, Toshihiko] National Hospital Organization, Kumamoto Medical Center, Department of PathologyKumamoto, Japan.
[Hidaka, Michihiro] National Hospital Organization, Kumamoto Medical Center, Department of Internal MedicineKumamoto, Japan.
[Kawano, Fumio] National Hospital Organization, Kumamoto Medical Center, Department of Internal MedicineKumamoto, Japan.
[Kitagawa, Masanobu] Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
RP Abe, Sh (reprint author), Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Department of Comprehensive Pathology, 113-8519 Tokyo, Japan.
EM abenchi.pth2@tmd.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 399
EP 407
DI 10.1007/s12253-013-9709-y
PG 9
ER
PT J
AU Kim, K
Kim, DH
Chae, WS
Shin, JH
Kim, JH
Do, SI
Lee, JH
Koo, HJ
Pyo, JS
Sohn, HJ
AF Kim, Kyungeun
Kim, Dong-Hoon
Chae, Wan Seoung
Shin, Jun-Ho
Kim, Joo Hong
Do, Sung-Im
Lee, Joo Hyun
Koo, Hae Ji
Pyo, Jung-Soo
Sohn, Hee Jin
TI Expression of Cell Cycle-Related Proteins, p16, p53 and p63 as Important Prognostic Markers in Gallbladder Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder; Adenocarcinoma; p16 protein; p53 protein; p63 protein
ID Gallbladder; Adenocarcinoma; p16 protein; p53 protein; p63 protein
AB Gallbladder cancer, the most common biliary tract malignancy, is a highlymalignant neoplasm. In the present work, we have analyzed the significance of cell cycle-related proteins to predict prognosis and to provide guidance for optimal therapeutic decision-making in patients with gallbladder adenocarcinoma. The expressions of p16, p21, p27, p53, p63, cyclin D1, bcl-2 and bcl-6 were examined in a tissue microarray constructed from 96 cases of gallbladder adenocarcinoma by immunohistochemistry and correlated with clinicopathologic prognostic factors. Expression of p16 was correlated with a low pT stage, adenoma background and good prognosis. Cases with p63 expression showed a higher T stage, more frequent perineural invasion and poor prognosis when compared to cases without p63 expression. Over-expression of p53 or loss of p53 was associated with poor tumor differentiation, frequent distant metastasis and low disease-specific survival rate. The expressions of p21, p27, bcl- 2, bcl-6 and cyclin D1 were not significant prognostic factors for gallbladder adenocarcinoma. These results indicate that p16, p63 and p53 can be used as prognostic markers in gallbladder adenocarcinoma; especially p53 and p63 as poor prognostic markers and p16 as a favorable prognostic marker.
C1 [Kim, Kyungeun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Kim, Dong-Hoon] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Chae, Wan Seoung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Shin, Jun-Ho] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Kim, Joo Hong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Internal MedicineSeoul, South Korea.
[Do, Sung-Im] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Lee, Joo Hyun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Koo, Hae Ji] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Pyo, Jung-Soo] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
[Sohn, Hee Jin] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 108, Pyeong-dong, Jongro-gu, 100-634 Seoul, South Korea.
RP Sohn, HJ (reprint author), Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 100-634 Seoul, South Korea.
EM jhpath.sohn@samsung.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 409
EP 415
DI 10.1007/s12253-013-9710-5
PG 7
ER
PT J
AU Virag, J
Kenessey, I
Haberler, Ch
Piurko, V
Balint, K
Dome, B
Timar, J
Garami, M
Hegedus, B
AF Virag, Jozsef
Kenessey, Istvan
Haberler, Christine
Piurko, Violetta
Balint, Katalin
Dome, Balazs
Timar, Jozsef
Garami, Miklos
Hegedus, Balazs
TI Angiogenesis and Angiogenic Tyrosine Kinase Receptor Expression in Pediatric Brain Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Astrocytoma; Ependymoma; Medulloblastoma; Tyrosine kinase receptor; Targeted therapy
ID Astrocytoma; Ependymoma; Medulloblastoma; Tyrosine kinase receptor; Targeted therapy
AB Tumor angiogenesis and receptor tyrosine kinases (RTK) are major novel targets in anticancer molecular therapy. Accordingly, we characterized the vascular network and the expression pattern of angiogenic RTK in the most frequent pediatric brain tumors. In a retrospective collection of 44 cases (14 astrocytoma, 16 ependymoma and 14 medulloblastoma), immunohistochemistry for VEGFR1, VEGFR2, PDGFRα, PDGFRβ, and c-Kit as well as microvessel labeling with CD34 and SMA were conducted on surgical specimens. We found a significantly higher vascular density in ependymoma. Glomeruloid formations were abundant in medulloblastoma but rare or almost absent in astrocytoma and ependymoma, respectively. C-Kit and VEGFR2 labeled blood vessels were more abundant in ependymoma than in the other two types of tumors. In contrast, medulloblastoma contained higher number of PDGFRα expressing vessels. In tumor cells, we found no VEGFR2 but VEGFR1 expression in all three tumor types. PDGFRαwas strongly expressed on the tumor cells in all three malignancies, while PDGFRβ tumor cell expression was present in the majority of medulloblastoma cases. Interestingly, small populations of c-Kit expressing cancer cells were found in a number of medulloblastoma and ependymoma cases. Our study suggests that different angiogenic mechanisms are present in ependymoma and medulloblastoma. Furthermore ependymoma patients may benefit from anti-angiogenic therapies based on the high vascularization as well as the endothelial expression of c-kit and VEGFR2. The expression pattern of the receptors on tumor cells also suggests the targeting of specific angiogenic tyrosine kinase receptors may have direct antitumor activity. Further preclinical and biomarker driven clinical investigations are needed to establish the application of tyrosine kinase inhibitors in the treatment of pediatric brain tumors.
C1 [Virag, Jozsef] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Haberler, Christine] Medical University of Vienna, Department of NeuropathologyVienna, Austria.
[Piurko, Violetta] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Balint, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Dome, Balazs] Medical University of Vienna, Department of Thoracic SurgeryVienna, Austria.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Garami, Miklos] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Hegedus, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Hegedus, B (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM balazs.hegedus@meduniwien.ac.at
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 417
EP 426
DI 10.1007/s12253-013-9711-4
PG 10
ER
PT J
AU Moghbeli, M
Forghanifard, MM
Aarabi, A
Mansourian, A
Abbaszadegan, RM
AF Moghbeli, Meysam
Forghanifard, Mahdi Mohammad
Aarabi, Azadeh
Mansourian, Akram
Abbaszadegan, Reza Mohammad
TI Clinicopathological Sex- Related Relevance of Musashi1 mRNA Expression in Esophageal Squamous Cell Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Musashi1 (Msi1); Expressional analysis; Real-time PCR
ID Esophageal squamous cell carcinoma; Musashi1 (Msi1); Expressional analysis; Real-time PCR
AB The cancer stem cell theory is considered as the spotlight of cancer biology, in which a subpopulation of tumor cells show unlimited proliferative and self renewal capacities. Post-transcriptional regulation is involved in different cellular functions such as cell differentiation and proliferation which results in cellular diversity. Musashi1 (Msi1) is one of the most important RNA-binding proteins (RBPs) which are involved in translational inhibition. Although, Msi1 targets are largely unknown, p21WAF-1, a cell cycle regulator, and Numb, inhibitor of notch signaling pathway, are well-known factors which are suppressed by the Msi1 in normal and cancer stem cells. Msi1 expression in tumor tissues from 53 ESCC patients was compared to normal tissues using realtime polymerase chain reaction (PCR). Msi1 was significantely overexpressed in 41.5 % of tumor samples and we observed a significant correlation between Msi1 expression and sex, in which the males had shown a higher level of Msi1 expression in comparison with the females (2.00 Vs 0.78 fold changes, p =0.05). In this study, we assessed whether Msi1 is expressed in ESCC samples suggesting this protein as a novel cancer stem cell marker which requires further studies.
C1 [Moghbeli, Meysam] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
[Forghanifard, Mahdi Mohammad] Islamic Azad University, Damghan Branch, Department of BiologyDamghan, Iran.
[Aarabi, Azadeh] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
[Mansourian, Akram] Mashhad University of Medical Sciences, Ghaem Hospital, Department of PathologyMashhad, Iran.
[Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
RP Abbaszadegan, RM (reprint author), Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
EM abbaszadeganmr@mums.ac.ir
CR Gholamin M, Moaven O, Memar B, Farshchian M, Naseh H, Malekzadeh R, Sotoudeh M, Rajabi-Mashhadi MT, Forghani MN, Farrokhi F, Abbaszadegan MR, 2009, Overexpression and interactions of interleukin-10, transforming growth factor beta, and vascular endothelial growth factor in esophageal squamous cell carcinoma. World J Surg 33(7):1439–1445
Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA, 2008, An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40(5):499–507
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 427
EP 433
DI 10.1007/s12253-013-9712-3
PG 7
ER
PT J
AU Zhang, F
Yang, J
Li, Z
AF Zhang, Fan
Yang, Junlan
Li, Zijian
TI Trastuzumab-Induced Systemic Capillary Leak Syndrome in a Breast Cancer Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SCLS; Trastuzumab; Chemotherapy; Breast cancer
ID SCLS; Trastuzumab; Chemotherapy; Breast cancer
AB Systemic capillary leak syndrome (SCLS) is a rare health condition. It is characterized by recurrent episodes of generalized edema and severe hypotension along with hypoproteinemia. The condition is under recognized because of its nonspecific signs and symptoms, and high mortality rate. SCLS triggered by trastuzumab, a target drug for Her2- positive breast cancer patients, has not been previously reported. A 59-year-old Chinese woman, diagnosed with breast cancer with accompanying liver and bone metastasis, was treated with 3 cycles of docetaxel with capecitabine and a regimen of 12 cycles of capecitabine with trastuzumab. The patient developed systemic capillary leak syndrome during the 16th cycle of chemotherapy. Post-diagnosis treatment regimen is also presented in the current case report. SCLS has been previously observed in breast cancer patients. However, SCLS incidence post-chemotherapeutic treatment with trastuzumab has not been reported elsewhere. Hence, our report highlights the need for rigorous investigation of the side effects of trastuzumab usage and the increasing need of insightful diagnosis to manage any incidence of SCLS. The case provides valuable experience for treating the uncommon adverse effects of trastuzumab in Her2-positive breast cancer patients.
C1 [Zhang, Fan] PLA General Hospital, Tumor Center, Key LaboratoryBeijing, China.
[Yang, Junlan] PLA General Hospital, Tumor Center, Oncology Department, No. 28 Fuxing Road, Haidian District, 100853 Beijing, China.
[Li, Zijian] PLA No.161 Hospital, Oncology DepartmentWuhan, China.
RP Yang, J (reprint author), PLA General Hospital, Tumor Center, Oncology Department, 100853 Beijing, China.
EM yangjunlan1123@126.com
CR Clarkson B, Thompson D, Horwith M et al, 1960, Cyclical edema and shock due to increased capillary permeability. Am J Med 29:193–216
Dhir V, Arya V, Malav IC et al, 2007, Idiopathic systemic capillary leak syndrome, SCLS): case report and systematic review of cases reported in the last 16 years. Intern Med 46:899–904
de Martino M, Sasso L, Pirozzi F et al, 2009, Systemic capillary leak syndrome or Clarkson’s disease: a case report. Intern Emerg Med 4: 357–358
Druey KM, Greipp PR, 2010, Narrative review: the systemic capillary leak syndrome. Ann Intern Med 153:90–98
Hollenberg J, Frykman J, Lundberg LG et al, 2010, A case report of systemic capillary leak syndrome, Clarkson’s disease). Acta Anaesthesiol Scand 54:649–652
Guillaume M, Tolsma V, Colombe B et al, 2011, Idiopathic systemic capillary leak syndrome: a case report with cardiac involvement. Rev Med Interne 32:e69–e71
Hudis CA, 2007, Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med 357:39–51
Bencsath KP, Reu F, Dietz J et al, 2011, Idiopathic systemic capillary leak syndrome preceding diagnosis of infiltrating lobular carcinoma of the breast with quiescence during neoadjuvant chemotherapy. Mayo Clin Proc 86:260–261
Kai-Feng W, Hong-Ming P, Hai-Zhou L et al, 2011, Interleukin-11- induced capillary leak syndrome in primary hepatic carcinoma patients with thrombocytopenia. BMC Cancer 11:204
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 435
EP 437
DI 10.1007/s12253-013-9713-2
PG 3
ER
PT J
AU Xu, D
Yu, Y
Zhu, Y
Huang, T
Chen, Y
Qi, J
AF Xu, Ding
Yu, Yongjiang
Zhu, Yunkai
Huang, Tao
Chen, Yaqing
Qi, Jun
TI A new Model Consists of Intravesical Prostatic Protrusion, Prostate Volume and Serum Prostatic-Specific Antigen in the Evaluation of Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intravesical prostatic protrusion; Prostate specific antigen; Prostate cancer; Diagnostic accuracy
ID Intravesical prostatic protrusion; Prostate specific antigen; Prostate cancer; Diagnostic accuracy
AB The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiveroperator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0–10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.
C1 [Xu, Ding] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UrologyShanghai, China.
[Yu, Yongjiang] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UrologyShanghai, China.
[Zhu, Yunkai] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UltrasoundShanghai, China.
[Huang, Tao] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UrologyShanghai, China.
[Chen, Yaqing] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UltrasoundShanghai, China.
[Qi, Jun] XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of UrologyShanghai, China.
RP Qi, J (reprint author), XinHua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine, Department of Urology, Shanghai, China.
EM qijunqijunqqjj@hotmail.com
CR Stephan C, Jung K, Lein M, Diamandis EP, 2007, PSA and other tissue kallikreins for prostate cancer detection. Eur J Cancer 43(13): 1918–1926., DOI 10.1016/j.ejca.2007.06.006
Tchetgen MB, Oesterling JE, 1997, The effect of prostatitis, urinary retention, ejaculation, and ambulation on the serum prostate-specific antigen concentration. Urol Clin North Am 24(2):283–291
Schroder FH, Roobol MJ, 2009, Defining the optimal prostatespecific antigen threshold for the diagnosis of prostate cancer. Curr Opin Urol 19(3):227–231., DOI 10.1097/MOU.0b013e328329a2d0
Lee JW, Ryu JH, Yoo TK, Byun SS, Jeong YJ, Jung TY, 2012, Relationship between Intravesical prostatic protrusion and postoperative outcomes in patients with benign prostatic hyperplasia. Korean J Urol 53(7):478–482., DOI 10.4111/kju.2012.53.7.478
Lim KB, Ho H, Foo KT, Wong MY, Fook-Chong S, 2006, Comparison of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of bladder outlet obstruction. Int J Urol 13(12):1509–1513., DOI 10.1111/j. 1442-2042.2006.01611.x
Lee LS, Sim HG, Lim KB, Wang D, Foo KT, 2010, Intravesical prostatic protrusion predicts clinical progression of benign prostatic enlargement in patients receiving medical treatment. Int J Urol 17(1): 69–74., DOI 10.1111/j.1442-2042.2009.02409.x
Yuen JS, Ngiap JT, Cheng CW, Foo KT, 2002, Effects of bladder volume on transabdominal ultrasound measurements of intravesical prostatic protrusion and volume. Int J Urol 9(4):225–229
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Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, Richie JP, deKernion JB,Walsh PC, Scardino PT, Lange PH, Subong EN, Parson RE, Gasior GH, Loveland KG, Southwick PC, 1998, Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 279(19): 1542–1547
Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH, SlawinKM, Marks LS, Loeb S, BroylesDL, Shin SS,CruzAB, Chan DW, Sokoll LJ, Roberts WL, van Schaik RH, Mizrahi IA, 2011, A multicenter study of [−2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. J Urol 185(5):1650–1655., DOI 10.1016/j.juro.2010.12.032
Reis LO, Barreiro GC, Baracat J, Prudente A, D’Ancona CA, 2008, Intravesical protrusion of the prostate as a predictive method of bladder outlet obstruction. Int Braz J Urol 34(5):627–633, discussion 634–627
Chia SJ, Heng CT, Chan SP, Foo KT, 2003, Correlation of intravesical prostatic protrusion with bladder outlet obstruction. BJU Int 91(4):371–374
Nose H, Foo KT, Lim KB, Yokoyama T, Ozawa H, Kumon H, 2005, Accuracy of two noninvasive methods of diagnosing bladder outlet obstruction using ultrasonography: intravesical prostatic protrusion and velocity-flow video urodynamics. Urology 65(3):493–497., DOI 10.1016/j.urology.2004.10.014
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 439
EP 443
DI 10.1007/s12253-013-9714-1
PG 5
ER
PT J
AU Lu, Rl
Hu, ChP
Yang, Hp
Li, Yy
Gu, Qh
Wu, L
AF Lu, Rong-li
Hu, Cheng-Ping
Yang, Hua-ping
Li, Yuan-yuan
Gu, Qi-hua
Wu, Lielin
TI Biological Characteristics and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Efficacy of EGFR Mutation and its Subtypes in Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma (LAC); Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; Exon 19 deletions (del 19); Exon 21 point mutation (L858R)
ID Lung adenocarcinoma (LAC); Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; Exon 19 deletions (del 19); Exon 21 point mutation (L858R)
AB Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in lung adenocarcinoma (LAC). In this study, we extensively investigated the impact of patients’ biological characteristics on EGFR mutation and the impact of EGFR mutation subtypes on targeted therapy of advanced LAC. We examined EGFR exons18to21status in169 LAC patients by direct sequencing to study the impact of patients’ biological characteristics on the EGFR mutational spectrum. And then, 59 patients with advanced LAC harboring EGFR exon 19 deletions(del 19) or exon 21 point mutation(L858R) mutations received first-line treatment of gefitinib or erlotinib, the efficacy of treatment, and the progression-free survival (PFS) of these patients were recorded. The frequency of the EGFR mutation and its subtypes and the variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using all samples (n =169). The EGFR mutation was significantly associated with well-differentiated tumor and excessive household cooking fumes(P <0.05). The deletions in exon 19 were more frequently associated with well-differentiated tumor (P <0.05). The overall frequency of the EGFR mutation was 49%. Then the impact of EGFR mutation subtypes on targeted therapy were investigated by the retrospective analysis on 59 advanced LAC patients with del 19 or L858R mutations and treated first-line with erlotinib or gefitinib. The deletions in exon 19 got longer PFS (P < 0.05). But there were no differences in PFS between erlotinib therapy and gefitinib therapy. EGFR mutations were more frequently in high tumor differentiation and excessive household cooking fumes LAC. The del 19 mutation rate is relatively high with a high differentiation degree in advanced lung adenocarcinoma. The deletions in exon 19 may benefit more from first-line targeted therapy of advanced LAC compared with exon 21 point mutation L858R. There was no significant difference between the efficacy of gefitinib and erlotinib treatments associated with EGFR mutation and its subtypes.
C1 [Lu, Rong-li] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Hu, Cheng-Ping] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Yang, Hua-ping] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Li, Yuan-yuan] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Gu, Qi-hua] Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, Hunan, China.
[Wu, Lielin] Central South University, Xiangya Hospital, Department of General Surgery, 410008 Changsha, Hunan, China.
RP Hu, ChP (reprint author), Central South University, Xiangya Hospital, Department of Respiratory, 410008 Changsha, China.
EM huchengp28@126.com
CR Siegel R, Naishadham D, Jemal A, 2012, Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29
Herbst RS, Heymach JV, Lippman SM(2008, Lung cancer. N Engl J Med 359(13):1367–1380
Mok TS, Wu YL, Thongprasert S et al, 2009, Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957
Mitsudomi T, Morita S, Yatabe Y et al, 2010, Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor, WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11(2):121–128
Lynch TJ, Bell DW, Sordella R et al, 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129– 2139
Paez JG, Janne PA, Lee JC et al, 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500
Mok TS, Wu YL, Thongprasert S et al, 2009, Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957
Yang CH, Yu CJ, Shih JY et al, 2008, Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 26(16):2745–2753
Rosell R, Moran T, Queralt C et al, 2009, Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967
Thatcher N, Chang A, Parikh P et al, 2005, Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study, Iressa Survival Evaluation in Lung Cancer). Lancet 366(9496):1527–1537
Shepherd FA, Rodrigues PJ, Ciuleanu T et al, 2005, Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132
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Miao-Jin F, Hai-Gang L, Zhi-Qiang L et al, 2011, Relationship of epidermal growth factor receptor gene mutations, clinicopathologic features and prognosis in patients with non-small cell lung cancer. Chinese J Pathol 40(10):679–682
Tomizawa Y, Iijima H, Sunaga N et al, 2005, Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer. Clin Cancer Res 11(19 Pt 1):6816–6822
Tam IY, Chung LP, Suen WS et al, 2006, Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res 12(5):1647–1653
Rosell R, Moran T, Queralt C et al, 2009, Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967
Shigematsu H, Gazdar AF, 2006, Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 118(2):257–262
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Kim ST, Uhm JE, Lee J et al, 2012, Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer 75(1):82–88
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 445
EP 451
DI 10.1007/s12253-013-9715-0
PG 7
ER
PT J
AU Paschke, L
Rucinski, M
Ziolkowska, A
Zemleduch, T
Malendowicz, W
Kwias, Z
Malendowicz, KL
AF Paschke, Lukasz
Rucinski, Marcin
Ziolkowska, Agnieszka
Zemleduch, Tomasz
Malendowicz, Witold
Kwias, Zbigniew
Malendowicz, K Ludwik
TI ZFP91—A Newly Described Gene Potentially Involved in Prostate Pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Benign prostate hyperplasia; Prostate cancer; Prostate cancer cell lines; ZFP91
ID Benign prostate hyperplasia; Prostate cancer; Prostate cancer cell lines; ZFP91
AB In search for novel molecular targets in benign prostate hyperplasia (BPH), a PCR Array based screening of 84 genes was performed. Of those, expression of ZFP91 (ZFP91 zinc finger protein) was notably upregulated. Limited data concerning the function of ZFP91 product show that it is a potential transcription factor upregulated in human acute myelogenous leukemia and most recently found to be the noncanonical NF-κB pathway regulator. In order to test this finding on a larger number of samples, prostate specimens were obtained from patients undergoing adenomectomy for BPH (n =21), and as a control, from patients undergoing radical cystectomy for bladder cancer (prostates unchanged pathologically, n =18). Similar studies were performed on cultured human prostate cancer cell lines: LNCaP, DU145, 22Rv1, PC-3; as well as normal prostate epithelial cells-PrEC. Methods employed included: Human Obesity PCR Array (Qiagen), QPCR and Western blotting. QPCR studies confirmed significant overexpression of ZFP91 in BPH samples. On a protein level, however, comparison between normal and BPH prostates revealed insignificant differences. As for prostate cell lines examined, all expressed ZFP91 mRNA. Western blotting analysis showed markedly higher protein levels of ZFP91 in all cancer cell lines in comparison with normal (PrEC) cells. In conclusion, the upregulated ZFP91 mRNA in BPH, not accompanied by parallel changes in ZFP91 protein levels, together with ZFP91 protein abundance in prostate cancer cell lines suggest ZFP91 involvement in these prostate diseases.
C1 [Paschke, Lukasz] Poznan University of Medical Sciences, Department of Histology and Embryology, 6 Swiecicki St, 60-781 Poznan, Poland.
[Rucinski, Marcin] Poznan University of Medical Sciences, Department of Histology and Embryology, 6 Swiecicki St, 60-781 Poznan, Poland.
[Ziolkowska, Agnieszka] Poznan University of Medical Sciences, Department of Histology and Embryology, 6 Swiecicki St, 60-781 Poznan, Poland.
[Zemleduch, Tomasz] Poznan University of Medical Sciences, Department of Histology and Embryology, 6 Swiecicki St, 60-781 Poznan, Poland.
[Malendowicz, Witold] Poznan University of Medical Sciences, Department of Histology and Embryology, 6 Swiecicki St, 60-781 Poznan, Poland.
[Kwias, Zbigniew] Poznan University of Medical Sciences, Department of Urology and UrooncologyPoznan, Poland.
[Malendowicz, K Ludwik] Poznan University of Medical Sciences, Department of Urology and UrooncologyPoznan, Poland.
RP Paschke, L (reprint author), Poznan University of Medical Sciences, Department of Histology and Embryology, 60-781 Poznan, Poland.
EM paschkelukasz@gmail.com
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Paschke L, Zemleduch T, Rucinski M, Ziolkowska A, Szyszka M, Malendowicz LK, 2010, Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis. Peptides 31:1715–1724
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 453
EP 459
DI 10.1007/s12253-013-9716-z
PG 7
ER
PT J
AU Liu, K
Gu, MM
Chen, HL
You, QSh
AF Liu, Kun
Gu, Ming-Ming
Chen, Hong-Lin
You, Qing-Sheng
TI NOB1 in Non-small-cell Lung Cancer: Expression Profile and Clinical Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small-cell lung cancer; NOB1; Tumor–specific gene
ID Non-small-cell lung cancer; NOB1; Tumor–specific gene
AB Nin one binding (NOB1) gene has been reported up-regulated in several types of cancer. The aim of this study was to investigate the expression profile of NOB1 in nonsmall- cell lung cancer (NSCLC) and assess the clinical significance. qRT-PCR was used in the detection of NOB1 mRNA expression both in NSCLC tissue and in adjacent normal lung tissue. Western blot analysis and immunohistochemistry were used in the detection of NOB1 protein expression. The clinicopathological implications of NOB1 were analyzed statistically. It was confirmed by RT-qPCR that expression of NOB1 mRNA in NSCLC cells was higher than in human lung cells (P <0.05), and NOB1 mRNA was also over-expressed in NSCLC tissue when compared with adjacent tissue and normal lung tissue (P <0.05). Western blot analysis showed that NOB1 protein was significant increased in NSCLC cell lines compared with human lung cell line. Western blot analysis and immunohistochemistry showed that NOB1 protein was significant increased in NSCLC tissue compared with adjacent tissue and normal lung tissue (P <0.05). There were significant associations between NOB1 expression and TNM stage, lymph node metastasis, and histopathological grade (P <0.05), but not gender, age, smoke, or tumor diameter (P >0.05). Our results suggest that enhanced expression of NOB1 gene plays an important role in the occurrence and development of NSCLC. NOB1 may be a potential therapeutic target in NSCLC.
C1 [Liu, Kun] Affiliated Hospital of Nantong University, Department of Cardiothoracic Surgery, Xi Si Road 20#, 226001 Nantong, Jiangsu Province, China.
[Gu, Ming-Ming] Affiliated Hospital of Nantong University, Department of Cardiothoracic Surgery, Xi Si Road 20#, 226001 Nantong, Jiangsu Province, China.
[Chen, Hong-Lin] Nantong University, Qi Xiu Road 19#, 226001 Nantong, Jiangsu Province, China.
[You, Qing-Sheng] Affiliated Hospital of Nantong University, Department of Cardiothoracic Surgery, Xi Si Road 20#, 226001 Nantong, Jiangsu Province, China.
RP You, QSh (reprint author), Affiliated Hospital of Nantong University, Department of Cardiothoracic Surgery, 226001 Nantong, China.
EM pphss@126.com
CR Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA Cancer J Clin 61(2):69–90
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Lin S,MengW, ZhangWet al, 2013, Expression of the NOB1 gene and its clinical significance in papillary thyroid carcinoma. J Int Med Res 41(3):568–572
Lin Y, Peng S, Yu H, Teng H, Cui M, 2012, RNAi-mediated downregulation of NOB1 suppresses the growth and colonyformation ability of human ovarian cancer cells. Med Oncol 29(1): 311–317
Lu Z, Guo Q, Shi A, Xie F, Lu Q, 2012, Downregulation of NIN/ RPN12 binding protein inhibit the growth of human hepatocellular carcinoma cells. Mol Biol Rep 39(1):501–507
Huang WY, Chen DH, Ning L, Wang LW, 2012, siRNA mediated silencing of NIN1/RPN12 binding protein 1 homolog inhibits proliferation and growth of breast cancer cells. Asian Pac J Cancer Prev 13(5):1823–1827
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Oyama T, Osaki T, Baba T, Nagata Y, Mizukami M, So T, Nakata S, Ichiki Y, Uramoto H, Sugaya M, Yoshimatsu T, Morita M, Hanagiri T, Sugio K, Kawamoto T, Yasumoto K, 2005, Molecular genetic tumor markers in non-small cell lung cancer. Anticancer Res 25(2B): 1193–1196
Tone Y, Tanahashi N, Tanaka K, Fujimuro M, Yokosawa H, Toh-e A, 2000, NOB1p, a new essential protein, associates with the 26S proteasome of growing saccharomyces cerevisiae cells. Gene 243(1–2):37–45
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Tu Y, Chen C, Pan J, Xu J, Zhou ZG,Wang CY(2012, The Ubiquitin Proteasome Pathway, UPP, in the regulation of cell cycle control and DNA damage repair and its implication in tumorigenesis. Int J Clin Exp Pathol 5(8):726–738
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 461
EP 466
DI 10.1007/s12253-013-9717-y
PG 6
ER
PT J
AU Grigoryeva, SE
Cherdyntseva, VN
Karbyshev, SM
Volkomorov, VV
Stepanov, I
Zavyalova, VM
Perelmuter, MV
Buldakov, AM
Afanasjev, GS
Tuzikov, AS
Bukurova, AY
Lisitsyn, AN
Beresten, FS
AF Grigoryeva, S Evgeniya
Cherdyntseva, V Nadezhda
Karbyshev, S Mikhail
Volkomorov, V Viktor
Stepanov, IvanV
Zavyalova, V Marina
Perelmuter, M Vladimir
Buldakov, A Mikhail
Afanasjev, G Sergey
Tuzikov, A Sergey
Bukurova, A Yulia
Lisitsyn, A Nikolai
Beresten, F Sergey
TI Expression of Cyclophilin A in Gastric Adenocarcinoma Patients and Its Inverse Association with Local Relapses and Distant Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Stomach cancer; Two-dimensional gel electrophoresis; Proteomics; Mass spectrometry; Cancer markers
ID Stomach cancer; Two-dimensional gel electrophoresis; Proteomics; Mass spectrometry; Cancer markers
AB The aim of this study was to identify new protein markers of the intestinal and diffuse type gastric adenocarcinoma and to determine their relation to local relapses and distantmetastasis. Using two-dimensional gel electrophoresis, we searched for proteins that are overexpressed in the intestinal and/or diffuse type gastric adenocarcinoma, as compared to matched normal mucosa samples with further change confirmation by Western blot. Expression of the selected proteins was further assessed by immunohistocemistry in a large panel of gastric adenocarcinoma with various clinicopathological features. Expression level of cyclophilin A measured with western blot appeared to be increased on average ten times in 63 % of gastric adenocarcinoma vs. paired samples of normal mucosa. The frequency of immunihistochemistry detected cyclophilin A protein expression was found to be equal in tumor of both histotypes, but staining intensity was higher in intestinal versus diffuse types of gastric adenocarcinoma. cyclophilin A protein expression appeared to be lower in deeply invading glandular and cribriform structures of intestinal tumors, as well as in discretely placed groups of the intestinal tumor cells. Local relapses as well as distant metastases registered within 3 year follow up were observed to occur much less frequently in patients with positive cyclophilin A immunostaining in gastric tumors. Analysis of cyclophilin A expression has a potential value for prognosis of gastric adenocarcinoma recurrence and distant metastasis.
C1 [Grigoryeva, S Evgeniya] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Cherdyntseva, V Nadezhda] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Karbyshev, S Mikhail] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Volkomorov, V Viktor] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Stepanov, IvanV] Siberian State Medical UniversityTomsk, Russian Federation.
[Zavyalova, V Marina] Siberian State Medical UniversityTomsk, Russian Federation.
[Perelmuter, M Vladimir] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Buldakov, A Mikhail] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Afanasjev, G Sergey] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Tuzikov, A Sergey] Siberian Branch of RAMS, Cancer Research Institute, 5 Kooperativny Street, 634050 Tomsk, Russian Federation.
[Bukurova, A Yulia] Russian Academy of Sciences, Engelhardt Institute of Molecular BiologyMoscow, Russian Federation.
[Lisitsyn, A Nikolai] Russian Academy of Sciences, Engelhardt Institute of Molecular BiologyMoscow, Russian Federation.
[Beresten, F Sergey] Russian Academy of Sciences, Engelhardt Institute of Molecular BiologyMoscow, Russian Federation.
RP Grigoryeva, SE (reprint author), Siberian Branch of RAMS, Cancer Research Institute, 634050 Tomsk, Russian Federation.
EM grigorieva@oncology.tomsk.ru
CR Jemal A, Center M, DeSantis C, Ward E, 2010, Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19(8):1893–1907
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Washington K, 2010, 7th Edition of the AJCC Cancer Staging Manual: Stomach. Ann Surg Oncol 17:3077–3079
VolkomorovV, Grigoryeva E, KrasnovG, Litviakov N, Tsyganov M, KarbyshevM, Zavyalova M, Afanasуev S, Cherdyntseva N, Lisitsyn N, Beresten S, 2013, Search for potential gastric cancer markers using miRNA databases and gene expression analysis. Exp Oncol 35(1):2–7
Obchoei S, Weakley SM, Wongkham S, Wongkham C, Sawanyawisuth K, Yao Q, Chen C, 2011, Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma. Mol Cancer 10:102
Nigro P, SatohK, O’DellM, SoeN, Cui Z,Mohan A,Abe J, Alexis J, Sparks J, Berk B, 2011, Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 208(1):53–66
Lee J, 2010, Role of Cyclophilin A during Oncogenesis. Arch Pharm Res 33:181–187
Campa MJ, Wang MZ, Howard B, Fitzgerald MC, Patz EF, 2003, Protein expression profiling identifies macrophage migration inhibitory factor and cyclophilin A as potential molecular targets in nonsmall-cell lung cancer. Cancer Res 63:1652–1656
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Lim SO, Park SJ, KimW, Park SG, Kim HJ, Kim YI, Sohn TS, Noh JH, Jung G, 2002, Proteome analysis of hepatocellular carcinoma. Biochem Biophys Res Commun 291:1031–1037
Yang J, Li A, Yang Y, Li X, 2011, Identification of cyclophilin A as a potential prognostic factor for clear-cell renal cell carcinoma by comparative proteomic analysis. Cancer Biol Ther 11(5):535–546
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Krasnov GS, Oparina NY, Hankin SL, Mashkova TD, Ershov AN, Zatsepina OG, Karpov VL, Beresten SF, 2009, Identification of proteins with altered expression in colorectal cancer by means of 2D-proteomics. Mol Biol, Mosk, 43:321–328
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Stepanov IV, Zavizlova MV, Grigor’eva ES, Bukurova YA, Afanas’ev SG, Cherdyntseva NV, 2010, Clinico-morphological and genetics features of diffuse and intestinal gastric adenocarcinomas. Siberian journal of oncology 40:55–66, in Russian)
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 467
EP 473
DI 10.1007/s12253-013-9718-x
PG 7
ER
PT J
AU Gou, X
Chen, H
Jin, F
Wu, W
Li, Y
Long, J
Gong, X
Luo, M
Bi, T
Li, Z
He, Q
AF Gou, Xiaoxia
Chen, Haixia
Jin, Feng
Wu, Weili
Li, Yuanyuan
Long, Jinhua
Gong, Xiuyun
Luo, Mengyalan
Bi, Ting
Li, Zhuolin
He, Qianyong
TI Expressions of CD147, MMP-2 and MMP-9 in Laryngeal Carcinoma and its Correlation with Poor Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laryngeal carcinoma; Extracellularmatrix metalloproteinase induced factor; Matrix metalloproteinase-2; Matrix metalloproteinase-9; Immunohistochemistry
ID Laryngeal carcinoma; Extracellularmatrix metalloproteinase induced factor; Matrix metalloproteinase-2; Matrix metalloproteinase-9; Immunohistochemistry
AB The objectives of this study are to investigate the expressions of matrix metalloproteinase inducing factor (CD147), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) in laryngeal tumor tissues and its significant correlation with tumor infiltration, metastasis and prognosis. Laryngeal tumor tissue from 48 laryngeal cancer patients with complete clinical information was collected. The laryngitis tissue from 15 patients were collected as control group. Immunohistochemical analysis for CD147, MMP-2 and MMP-9 was performed for all the tissue. The results showed the expression rates of CD147, MMP-2 and MMP-9 in laryngeal carcinoma were 87.5 %, 75.0 % and 79.2 % respectively, significantly higher than those (26.7 %, 6.7 %, and 33.3 % respectively) in the control group are (P <0.01). High expression of CD147, MMP-2 and MMP-9 related to the clinical stages and lymphatic metastasis of laryngeal carcinoma. Univariate survival analysis showed that the 5-year survival of laryngeal carcinoma patients with low expression of CD147, MMP-2 and MMP-9was 83.3 %, 83.3 % and 90 % respectively, while the patients with high expression had 5-year survival at 25 %, 7.7 % and 18.2 % respectively (P <0.05). Multiple regression analysis showed that high expression of MMP-9 was independently associated with poor prognosis (P <0.05). High expression of CD147, MMP-2 and MMP-9 were related with laryngeal carcinoma invasion and metastasis. High expressions of CD147,MMP-2 and MMP-9 were all predictive factors of poor prognosis of laryngeal carcinoma.
C1 [Gou, Xiaoxia] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Chen, Haixia] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Jin, Feng] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Wu, Weili] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Li, Yuanyuan] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Long, Jinhua] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Gong, Xiuyun] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Luo, Mengyalan] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Bi, Ting] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[Li, Zhuolin] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
[He, Qianyong] The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
RP Jin, F (reprint author), The Affiliated Hospital of Guiyang Medical College, Guizhou Cancer Hospital, Department of Oncology, 550003 Guiyang, China.
EM jinf8865@yeah.net
CR Nabeshima K, Iwasaki H, Koga K, Hojo H, Suzumiya J, Kikuchi M, 2006, Emmprin, basigin/CD147):matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int 56:359–367
Tang Y, Kesavan P, Nakada MT, Yan L, 2004, Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer, EMMPRIN, expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2:73–80
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Guo H, Li R, Zucker S, Toole BP, 2000, EMMPRIN, CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res 60:888–891
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Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, Xu HY, Song F, Yang XM, Mi L, Zhao QC, Tian R, Feng Q, Zhang SH, Li Y, Jiang JL, Li L, Yu XL, Zhang Z, Chen ZN, 2007, A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology 45:269–276
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Jia L,WeiW, Cao J, Xu H, Miao J, Zhang J, 2009, Silencing CD147 inhibits tumor progression and increases chemosensitivity inmurine lymphoid neoplasm P388D1 cells. Ann Hematol 88(8):753–760
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 475
EP 481
DI 10.1007/s12253-013-9720-3
PG 7
ER
PT J
AU Kapoor, Sh
AF Kapoor, Shailendra
TI Tumor Growth Attenuating Effects of Naringenin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kapoor, Shailendra] University of ChicagoChicago, IL, USA.
RP Kapoor, Sh (reprint author), University of Chicago, Chicago, USA.
EM shailendrakapoor@yahoo.com
CR Sulfikkarali N, Krishnakumar N, Manoharan S, Nirmal RM, 2012, Chemopreventive efficacy of naringenin-loaded nanoparticles in 7,12- dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Pathol Oncol Res 19:287–296
Sabarinathan D, Vanisree AJ, 2012, Plausible role of naringenin against cerebrally implanted C6 glioma cells in rats. Mol Cell Biochem 375:171–178
Sabarinathan D, Mahalakshmi P, Vanisree AJ, 2011, Naringenin, a flavanone inhibits the proliferation of cerebrally implanted C6 glioma cells in rats. Chem Biol Interact 189:26–36
Sabarinathan D, Mahalakshmi P, Vanisree AJ, 2010, Naringenin promote apoptosis in cerebrally implanted C6 glioma cells. Mol Cell Biochem 345:215–222
Ekambaram G, Rajendran P, Magesh V, Sakthisekaran D, 2008, Naringenin reduces tumor size and weight lost in N-methyl-N′-nitro- N-nitrosoguanidine-induced gastric carcinogenesis in rats. Nutr Res 28:106–112
Ekambaram G, Rajendran P, Devaraja R, Muthuvel R, Sakthisekaran D, 2008, Impact of naringenin on glycoprotein levels in N-methyl-N′- nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Anticancer Drugs 19:885–890
Subramanian P, Arul D, 2012, Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats. Cell Biochem Funct 31: 511–517
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2014
VL 20
IS 2
BP 483
EP 483
DI 10.1007/s12253-013-9702-5
PG 1
ER
PT J
AU Al-Dasooqi, N
Wardill, RH
Gibson, JR
AF Al-Dasooqi, Noor
Wardill, R Hannah
Gibson, J Rachel
TI Gastrointestinal Mucositis: The Role of MMP-Tight Junction Interactions in Tissue Injury
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Matrix metalloproteinases; Tight junctions; Gut toxicity; Mucositis; Chemotherapy
ID Matrix metalloproteinases; Tight junctions; Gut toxicity; Mucositis; Chemotherapy
AB Chemotherapy for cancer causes significant gut toxicity known as mucositis. The pathogenesis of mucositis is ill defined. Recent clinical research guidelines have highlighted epithelial junctional complexes as emerging targets within mucositis research. Given the robust biological evidence linking tight junctions and matrix metalloproteinases, key mediators of mucositis, tight junction proteins have received significant attention. Despite this, the link between tight junctions, matrix metalloproteinases and mucositis development is yet to be established. This critical review therefore aims to describe the role of matrix metalloproteinases in mucositis, and how matrix metalloproteinase-dependent tight junction disruption may contribute to the pathobiology of mucositis.
C1 [Al-Dasooqi, Noor] University of Adelaide, School of Medical Sciences, North Terrace, 5005 Adelaide, Australia.
[Wardill, R Hannah] University of Adelaide, School of Medical SciencesAdelaide, Australia.
[Gibson, J Rachel] University of Adelaide, School of Medical SciencesAdelaide, Australia.
RP Al-Dasooqi, N (reprint author), University of Adelaide, School of Medical Sciences, 5005 Adelaide, Australia.
EM noor.al-dasooqi@adelaide.edu.au
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 485
EP 491
DI 10.1007/s12253-013-9733-y
PG 7
ER
PT J
AU Holczbauer,
Gyongyosi, B
Lotz, G
Torzsok, P
Kaposi-Novak, P
Szijarto, A
Tatrai, P
Kupcsulik, P
Schaff, Zs
Kiss, A
AF Holczbauer, Agnes
Gyongyosi, Benedek
Lotz, Gabor
Torzsok, Peter
Kaposi-Novak, Pal
Szijarto, Attila
Tatrai, Peter
Kupcsulik, Peter
Schaff, Zsuzsa
Kiss, Andras
TI Increased Expression of Claudin-1 and Claudin-7 in Liver Cirrhosis and Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocarcinogenesis; Hepatitis C virus; Cirrhosis; Tight junction; Claudin
ID Hepatocarcinogenesis; Hepatitis C virus; Cirrhosis; Tight junction; Claudin
AB Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelialmesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV-infection. Expression of claudin-1, -2, -3, -4, and −7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding nontumorous tissues and 6 normal livers. Claudin-1 and −7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both nontumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV-infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation.
C1 [Holczbauer, Agnes] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Gyongyosi, Benedek] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Torzsok, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kaposi-Novak, Pal] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Szijarto, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Tatrai, Peter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kupcsulik, Peter] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
RP Kiss, A (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM kiss.andras@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 493
EP 502
DI 10.1007/s12253-013-9683-4
PG 10
ER
PT J
AU Rekhi, B
Vogel, U
Basak, R
Desai, BS
Jambhekar, AN
AF Rekhi, Bharat
Vogel, Ulrich
Basak, Ranjan
Desai, B Sangeeta
Jambhekar, A Nirmala
TI Clinicopathological and Molecular Spectrum of Ewing Sarcomas/PNETs, Including Validation of EWSR1 Rearrangement by Conventional and Array FISH Technique in Certain Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ewing sarcoma; PNET; EWS-FLI1; EWSR1 rearrangement; FISH in soft tissue tumors; Molecular pathology of soft tissue sarcomas; Array FISH
ID Ewing sarcoma; PNET; EWS-FLI1; EWSR1 rearrangement; FISH in soft tissue tumors; Molecular pathology of soft tissue sarcomas; Array FISH
AB Over the years, a wide clinicopathological spectrum has been identified within Ewing family of tumors (EFTs). As these tumors are chemosensitive, their correct and timely identification is necessary. The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test. Fifty-eight EFTs were identified in 38 males and 20 females within an age-range of 1–65 years (median, 16),mostly in lower extremities (14) (24.1 %). Therapeutically, most patients underwent neoadjuvant chemotherapy with subsequent surgery. Histopathologically, diagnosis of EFTs was initially offered in 41/58 (70.6 %) tumors. On review, 59 % tumors showed diffuse pattern, while 41 % displayed rosettes. Immunohistochemically, tumor cells were mostly diffusely positive for CD99 (48/52) (92.3 %); FLI-1 (17/18) (94.4 %); variably for BCL2 (16/18) (88.8 %), synaptophysin (6/20) (35 %), S100-P (2/7) (28.5 %), CD56 (2/5) (40 %), NSE (2/5) (40 %), calponin (3/4) (75 %), EMA (5/24) (20.8 %) and CK (3/24) (12.5%), the latter two mostly focally. Fifty five tumors were EWS-FLI1 positive, while a single tumor was EWS-ERG positive. Sensitivity for PCR was 61 %. EWSR1 rearrangement was detected by FISH in 12/13 Ewing sarcomas/ PNETs. Sensitivity for EWSR1 test was 92.3 % and specificity was 100 %. Thirty-eight tumors, including 14 molecular confirmed EFTs and 21 other tumors were tested for EWSR1 rearrangement. Among 21 unrelated tumors, EWSR1 rearrangement was detected in fewmyoepithelial tumors, occasional desmoplastic small round cell tumor and an extraskeletal myxoid chondrosarcoma. Further, a tissue microarray with a separate set of 8 EFTs, confirmed at another laboratory was analysed for validation of EWSR1 rearrangement test. 23/28 (82.1 %) tissue cores of the tissue microarray, stained by FISH were interpretable, including EWSR1 rearrangement, detected in 20/28 tissue cores; not detected in 3 liver cores and uninterpretable in 5 (17.8 %) cores. Classical EFTs can be diagnosed with diffuse, membranous CD99 positivity, intranuclear FLI1 positivity and LCA negativity in malignant round cells. In unconventional cases, it is indispensable to reveal the concomitant fusion m-RNA by RT-PCR. In case of negative molecular results, it is necessary to prove EWSR1 rearrangement by FISH. These tests should be interpreted with clinicopathological correlation. Tissue microarrays for FISH are useful during validation of a new test, especially when sarcomas like EFTs show less genetic heterogeneity within tumor cells.
C1 [Rekhi, Bharat] Tata Memorial Hospital, Department of Pathology, ParelMumbai, Maharashtra, India.
[Vogel, Ulrich] Eberhard-Karls-University, University Hospital Tuebingen, Institute of Pathology, Leibermeisterstrasse 8, 72076 Tuebingen, Germany.
[Basak, Ranjan] Tata Memorial Hospital, Department of Pathology, ParelMumbai, Maharashtra, India.
[Desai, B Sangeeta] Tata Memorial Hospital, Department of Pathology, ParelMumbai, Maharashtra, India.
[Jambhekar, A Nirmala] Tata Memorial Hospital, Department of Pathology, ParelMumbai, Maharashtra, India.
RP Rekhi, B (reprint author), Tata Memorial Hospital, Department of Pathology, Mumbai, India.
EM rekhi.bharat@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 503
EP 516
DI 10.1007/s12253-013-9721-2
PG 14
ER
PT J
AU Choi, JY
Yoo, JN
Lee, HS
AF Choi, Jin Youn
Yoo, Jin Nam
Lee, Hyung Sug
TI Down-regulation of ROBO2 Expression in Prostate Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ROBO2; Prostate cancer; Expression
ID ROBO2; Prostate cancer; Expression
AB Several lines of evidence exist that axon guidance genes are involved in cancer pathogenesis. Axon guidance genes ROBO1 and ROBO2 are candidate tumor suppressor genes (TSG). The aim of our study was to address whether ROBO1 and ROBO2 expressions are altered in prostate cancers (PCA). In this study, we analyzed ROBO1 and ROBO2 expressions in 107 PCAs. In the immunohistochemistry, loss of ROBO2 expression was identified in 66 % of PCAs and was significantly higher than that in normal cells (p< 0.001). By contrast, there was no significant difference of ROBO1 expression between normal and PCAs. Our results indicate that axon guidance protein ROBO2 is frequently lost in PCA and that ROBO2 might be involved in PCA pathogenesis as a candidate TSG.
C1 [Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Topczewska JM, Postovit LM, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff BJ, Topczewski J, Hendrix MJ, 2006, Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness. Nat Med 12:925–932
Mehlen P, Delloye-Bourgeois C, Chedotal A, 2011, Novel roles for Slits and netrins: axon guidance cues as anticancer targets. Nat Rev Cancer 11:188–197
Tseng RC, Lee SH, Hsu HS, Chen BH, TsaiWC, Tzao C,Wang YC, 2010, SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer Res 70:543–551
Prasad A, Paruchuri V, Preet A, Latif F, Ganju RK, 2008, Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. J Biol Chem 283:26624–26633
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Mitra S, Mazumder-Indra D, Mondal RK, Basu PS, Roy A, Roychoudhury S, Panda CK, 2012, Inactivation of SLIT2- ROBO1/2 pathway in premalignant lesions of uterine cervix: clinical and prognostic significances. PLoS One 7:e38342
Sundaresan V, Chung G, Heppell-Parton A, Xiong J, Grundy C, Roberts I, James L, Cahn A, Bench A, Douglas J, Minna J, Sekido Y, Lerman M, Latif F, Bergh J, Li H, Lowe N, Ogilvie D, Rabbitts P, 1998, Homozygous deletions at 3p12 in breast and lung cancer. Oncogene 17:1723–1729
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Ghosh S, Ghosh A, Maiti GP, Alam N, Roy A, Roychoudhury S, Panda CK(2009, Alterations of ROBO1/DUTT1 andROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications. Hum Genet 125:189–198
Latil A, Chene L, Cochant-Priollet B, Mangin P, Fournier G, Berthon P, Cussenot O, 2003, Quantification of expression of netrins, slits and their receptors in human prostate tumors. Int J Cancer 103:306–315
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Kim MS, Hur SY, Yoo NJ, Lee SH, 2010, Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol 221:147–152
Kim MS, Oh JE, Kim YR, Park SW, Kang MR, Kim SS, Ahn CH, Yoo NJ, Lee SH, 2010, Somatic mutations and losses of expression of microRNA regulation-related genes AGO2 and TNRC6A in gastric and colorectal cancers. J Pathol 221:139–146
Biankin AV, Waddell N, Kassahn KS et al, 2012, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 491:399–405
Ong CK, Subimerb C, Pairojkul C et al, 2012, Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet 44:690–693
Berger MF, Lawrence MS, Demichelis F et al, 2011, The genomic complexity of primary human prostate cancer. Nature 470:214–220
Barbieri CE, Baca SC, LawrenceMS et al, 2012, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44:685–689
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 517
EP 519
DI 10.1007/s12253-013-9722-1
PG 3
ER
PT J
AU Seki, S
Fujiwara, M
Matsuura, M
Fujita, Sh
Ikeda, H
Umeda, M
Asahina, I
Ikeda, T
AF Seki, Sachiko
Fujiwara, Mutsunori
Matsuura, Masaaki
Fujita, Shuichi
Ikeda, Hisazumi
Umeda, Masahiro
Asahina, Izumi
Ikeda, Tohru
TI Prognostic Value of Podoplanin Expression in Oral Squamous Cell Carcinoma―A Regression Model Auxiliary to UICC Classification
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Podoplanin; Oral squamous cell carcinoma; Prognosis; Clinical stage; Statistical analysis
ID Podoplanin; Oral squamous cell carcinoma; Prognosis; Clinical stage; Statistical analysis
AB Podoplanin, a type I transmembrane glycoprotein with an effect of platelet aggregation, has been reported to be one of the possible prognostic factors of oral squamous cell carcinoma (OSCC). However, the biological significance of podoplanin is largely unclear. The aim of this study was to develop a practicalmodel for the prediction of prognosis using the grade of podoplanin expression, and also to evaluate the biological function of podoplanin. Eighty-two specimens of patients with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed. These 82 cases were composed of 66 well-differentiated, 10 moderately differentiated and 6 poorly differentiated OSCC. Podoplanin was successfully immunostained in 78 specimens, and was detected in most cases, but the frequency of positive cells varied. The prognosis of patients with more than 50 % podoplaninpositive tumor cells was significantly poorer than that of the other patients. Multivariate hazards regression analysis suggested that a linear combination of covariates, OSCC patients with more or less than 50 % podoplanin expression, age of more or less than 70 years old,mode of invasion and T3, T4 or T2 versus T1 of the UICC T-stage classification was the most effective model for evaluating the prognosis of OSCC patients. Additionally, podoplanin expression had a significant relationship to UICC clinical stage and the expression of Ki- 67. An effective regression model using podoplanin expression was developed for evaluating the prognosis of OSCC and the biological significance of podoplanin was suggested to be associated with the growth and/or progression of OSCC.
C1 [Seki, Sachiko] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
[Fujiwara, Mutsunori] Japanese Red Cross Medical Center, Department of Clinical PathologyTokyo, Japan.
[Matsuura, Masaaki] Japanese Foundation for Cancer Research, Genome Center of JFCR, and Division of Cancer Genomics, Cancer Institute of JFCR, Bioinformatics GroupTokyo, Japan.
[Fujita, Shuichi] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
[Ikeda, Hisazumi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral SurgeryNagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Asahina, Izumi] Nagasaki University Graduate School of Biomedical Sciences, Department of Regenerative Oral SurgeryNagasaki, Japan.
[Ikeda, Tohru] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
RP Ikeda, T (reprint author), Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone Metabolism, Nagasaki, Japan.
EM tohrupth@nagasaki-u.ac.jp
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Kreppel M, Drebber U, Wedemeyer I, Eich HT, Backhaus T, Zoller JE, Scheer M, 2011, Podoplanin expression predicts prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy. Oral Oncol 47(9):873–878., DOI 10.1016/j. oraloncology.2011.06.508
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 521
EP 528
DI 10.1007/s12253-013-9723-0
PG 8
ER
PT J
AU Varszegi, D
Duga, B
Melegh, IB
Sumegi, K
Kisfali, P
Maasz, A
Melegh, B
AF Varszegi, Dalma
Duga, Balazs
Melegh, I Bela
Sumegi, Katalin
Kisfali, Peter
Maasz, Anita
Melegh, Bela
TI Hodgkin Disease Therapy Induced Second Malignancy Susceptibility 6q21 Functional Variants in Roma and Hungarian Population Samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hodgkin’s lymphoma; PRDM1; Genetics; Susceptibility
ID Hodgkin’s lymphoma; PRDM1; Genetics; Susceptibility
AB Patients treated successfully for pediatric Hodgkin’s lymphoma are known to develop secondary malignancies; care is already taken in treatment to prevent this adverse effect. Recent GWAS study identified rs4946728 and rs1040411 noncoding SNPs located between PRDM1 and ATG1 genes on chromosome 6q21 as risk factors for secondary malignancies in patients formerly treated with radiotherapy for pediatric Hodgkin disease. We investigated the allele frequencies of these two SNPs in biobanked, randomly selected DNA of average, apparently healthy Hungarians (n =277) and in samples of Roma (n =279) population living Hungary. The risk allele frequency for rs4946728 was 79.4 % in Hungarian and 83.5 % in Roma samples, while for rs1040411 it was 56.4%in Hungarian and 55.8%in Roma samples. These values are quite similar in the two populations, and are rather high. The values are higher than those frequencies observed in the controls (rs4946728: 59.1 % and rs1040411: 39.6 %, p < 0.05), and are in the range of the cases (86 % and 68.2 %, respectively) of the above original GWAS study. Our findings suggest, that beside the already taken precautions, genetic characterization of Hungarian pediatric Hodgkin patients seems to be advantageous prior to the treatment of their disease.
C1 [Varszegi, Dalma] University of Pecs, Department of Dermatology, Venereology and OncodermatologyPecs, Hungary.
[Duga, Balazs] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
[Melegh, I Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
[Sumegi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
[Kisfali, Peter] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, 7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, 7624 Pecs, Hungary.
EM bela.melegh@aok.pte.hu
CR Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL, Neglia JP, 2010, Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 102: 1083–1095
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 529
EP 533
DI 10.1007/s12253-013-9724-z
PG 5
ER
PT J
AU Chen, K
Wu, D
Bai, Y
Zhu, X
Chen, Z
Wang, Ch
Zhao, Y
Li, M
AF Chen, Kai
Wu, Dajiang
Bai, Yushu
Zhu, Xiaodong
Chen, Ziqiang
Wang, Chuanfeng
Zhao, Yingchuan
Li, Ming
TI Fuzzy Clustering Analysis of Osteosarcoma Related Genes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Gene sequences; Fuzzy clustering; Runx2
ID Osteosarcoma; Gene sequences; Fuzzy clustering; Runx2
AB Osteosarcoma is the most common malignant bone-tumor with a peak manifestation during the second and third decade of life. In order to explore the influence of genetic factors on the mechanism of osteosarcoma by analyzing the inter relationship between osteosarcoma and its related genes, and then provide potential genetic references for the prevention, diagnosis and treatment of osteosarcoma, we collected osteosarcoma related gene sequences in Genebank of National Center for Biotechnology Information (NCBI) and local alignment analysis for a pair of sequences was carried out to identify the measurement association among related sequences. Then fuzzy clustering method was used for clustering analysis so as to contact the unknown genes through the consistent osteosarcoma related genes in one class. From the result of fuzzy clustering analysis, we could classify the osteosarcoma related genes into two groups and deduced that the genes clustered into one group had similar function. Based on this knowledge, we found more genes related to the pathogenesis of osteosarcoma and these genes could exert similar function as Runx2, a risk factor confirmed in osteosarcoma, this study may help better understand the genetic mechanism and provide new molecular markers and therapies for osteosarcoma.
C1 [Chen, Kai] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Wu, Dajiang] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Bai, Yushu] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Zhu, Xiaodong] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Chen, Ziqiang] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Wang, Chuanfeng] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Zhao, Yingchuan] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
[Li, Ming] Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
RP Li, M (reprint author), Changhai Hospital, Department of Orthopedics, 200433 Shanghai, China.
EM minglil@hotmail.com
CR Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, 2002, Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 535
EP 539
DI 10.1007/s12253-013-9725-y
PG 5
ER
PT J
AU Sheng, L
Xiong, M
Li, C
Meng, X
AF Sheng, Long
Xiong, Maoming
Li, Cong
Meng, Xiangling
TI Reversing Multidrug-Resistant by RNA Interference Through Silencing MDR1 Gene in Human Hepatocellular Carcinoma Cells Subline Bel-7402/ADM
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma; siRNA; MDRl gene; Reversal; Bel-7402/ADM
ID Human hepatocellular carcinoma; siRNA; MDRl gene; Reversal; Bel-7402/ADM
AB Multidrug resistance (MDR) in hepatocellular carcinoma (HC) significantly impedes the effect of chemotherapy and is considered as a primary reason leading to its recurrences andmetastasis. The aimof present study was to explore new molecular targets for the reversal of MDR in HC by screening the adriamycin (ADM)-induced, human MDR-resistant HC cell subline Bel-7402/ADM. Small interfering RNAs (siRNAs) of four (MDR1si326, MDR1si1513, MDR1si2631 and MDR1si3071) targeting MDR1 were designed and transfected into Bel-7402/ADM cell strains. The experiments involved the following: mRNA expression of MDR1 gene by RT-PCR, P-glycoprotein (P-gp) expression by Western blot, intracellular ADM accumulation flow cytometry, and IC50 of ADM by a cytotoxic MTT assay. Four siRNAs reversed MDR in HC mediated by MDR1 to varying degrees. The expression level of MDR1 mRNA in cells of MDR1si326 or MDR1si2631 group (0.190±0.038 or 0.171± 0.011) was more decreased. The expression level of P-gp in cells of MDR1si326 group was the lowest. The accumulation of ADM in cells of MDR1si326 or MDR1si2631 group (77.0±3.5 or 75.4±2.9) was more increased. The IC50 of cells to ADM was lowest in MDR1si326 group (11.32±0.69 mg/L). Compared with other three siRNAs, MDR1si326 performed the optimal reversal effect of drug resistance in human HC Bel-7402/ADM.
C1 [Sheng, Long] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
[Xiong, Maoming] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
[Li, Cong] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
[Meng, Xiangling] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
RP Xiong, M (reprint author), The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
EM xiongmd@aliyun.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 541
EP 548
DI 10.1007/s12253-013-9726-x
PG 8
ER
PT J
AU Zhou, Y
Wan, Ch
Liu, Y
Lv, L
Chen, B
Ni, R
Huang, Y
Li, Y
Zheng, X
Yang, D
Mao, G
Xue, Q
AF Zhou, Yiqun
Wan, Chunhua
Liu, Yifei
Lv, Liting
Chen, Buyou
Ni, Runzhou
Huang, Yuexia
Li, Yangcheng
Zheng, Xiaodong
Yang, Dunpeng
Mao, Guoxin
Xue, Qun
TI Polycomb Group Oncogene RING1 is Over-expressed in Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; RING1; Prognosis
ID Non-small cell lung cancer; RING1; Prognosis
AB Ring finger protein 1 (RING1) have recently been reported to be related to aggressive tumor features in Prostate Cancer and urothelial carcinoma of the bladder. However, the role of RING1 in non-small-cell lung cancer (NSCLC) tumorigenesis has never been elucidated. So we aimed at investigating the potential role of RING1 in NSCLC. RING1 expression was evaluated by Immunoblot in 8 paired fresh lung cancer tissues and immunohistochemistry on 69 paraffinembedded sections from 2006 to 2009. Furthermore, flowcytometry and RNA interference were performed to analyse the role of RING1 in A549 cells. We showed that the expression level of RING1 was significant increased in lung cancer as compared with the adjacent normal tissue. High expression level of RING1 was associated with TNM stage (P =0.013), and RING1 was positively related with proliferation marker Ki67 (P <0.05). Moreover, RING1 knockdown induces growth suppression of human lung cancer cells through G1/ S cell cycle phase arrest in vitro. Kaplan–Meier survival curves showed that high expression level of RING1 was associated with poor prognosis (P =0.03). On the basis of these results, we suggested that RING1 protein expression may be a favorable independent prognostic parameter for non-small cell lung cancer.
C1 [Zhou, Yiqun] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 226001 Nantong, Jiangsu, China.
[Wan, Chunhua] Nantong University, Department of Public Health, 226001 Nantong, Jiangsu, China.
[Liu, Yifei] Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, Jiangsu, China.
[Lv, Liting] Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, Jiangsu, China.
[Chen, Buyou] Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, Jiangsu, China.
[Ni, Runzhou] Affiliated Hospital of Nantong University, Department of Gastroenterology, 226001 Nantong, Jiangsu, China.
[Huang, Yuexia] Affiliated Hospital of Nantong University, Department of Gastroenterology, 226001 Nantong, Jiangsu, China.
[Li, Yangcheng] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 226001 Nantong, Jiangsu, China.
[Zheng, Xiaodong] Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, Jiangsu, China.
[Yang, Dunpeng] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 226001 Nantong, Jiangsu, China.
[Mao, Guoxin] Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, Jiangsu, China.
[Xue, Qun] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 226001 Nantong, Jiangsu, China.
RP Mao, G (reprint author), Affiliated Hospital of Nantong University, Department of Oncology, 226001 Nantong, China.
EM ntmgx123@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 549
EP 556
DI 10.1007/s12253-013-9727-9
PG 8
ER
PT J
AU Fernandes, FB
Coates, J
Odashiro, NA
Quezada, C
Huynh, A
Odashiro, RP
Odashiro, M
Burnier, NM
AF Fernandes, F Bruno
Coates, James
Odashiro, N Alexandre
Quezada, Carlos
Huynh, Aimee
Odashiro, R Patricia
Odashiro, Macanori
Burnier, N Miguel
TI Hypoxia-Inducible Factor-1α and its Role in the Proliferation of Retinoblastoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hypoxic; Hypoxic-inducible factor; Retinoblastoma; Knockdown; Proliferation
ID Hypoxic; Hypoxic-inducible factor; Retinoblastoma; Knockdown; Proliferation
AB In order to better understand the role of HIF-1α in the proliferation of the retinoblastoma cells, a siRNA knockdown of HIF-1α followed by a proliferation assay was performed. Further sequencing was then carried out in order to assess knockdown efficiency and expression of HIF-1α. Upregulation of HIF-1α gene expression in CoCl2-treated retinoblastoma cells was demonstrated via melting curve analysis from PCR tests and was further analyzed using western blot and densitometry analysis. Reduction of HIF-1α expression in retinoblastoma, post HIF-1α knockdown, was observed after siRNA transfection into Y-79 cells. Knockdown of HIF-1α resulted in a significant decrease in proliferation thereby demonstrating that HIF-1α is involved in promoting survival and proliferation in retinoblastoma cells. Stabilization of HIF-1α in retinoblastoma cells using CoCl2 was unsuccessful.
C1 [Fernandes, F Bruno] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
[Coates, James] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
[Odashiro, N Alexandre] McMaster University, Department of Pathology and Molecular MedicineHamilton, ON, Canada.
[Quezada, Carlos] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
[Huynh, Aimee] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
[Odashiro, R Patricia] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
[Odashiro, Macanori] Federal University of Mato Grosso do SulCampo Grande, MS, Brazil.
[Burnier, N Miguel] The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, 3775 University St., Room 216, H3A 2B4 Montreal, QC, Canada.
RP Quezada, C (reprint author), The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology and Pathology, H3A 2B4 Montreal, Canada.
EM quezadarc@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 557
EP 563
DI 10.1007/s12253-013-9728-8
PG 7
ER
PT J
AU Ujj, Zs
Buglyo, G
Udvardy, M
Vargha, Gy
Biro, S
Rejto, L
AF Ujj, Zsofia
Buglyo, Gergely
Udvardy, Miklos
Vargha, Gyorgy
Biro, Sandor
Rejto, Laszlo
TI WT1 Overexpression Affecting Clinical Outcome in Non-Hodgkin Lymphomas and Adult Acute Lymphoblastic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE WT1 gene; Overexpression; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; Mantle cell lymphoma; Acute lymphoblastic leukemia
ID WT1 gene; Overexpression; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; Mantle cell lymphoma; Acute lymphoblastic leukemia
AB The Wilms tumor 1 (WT1) gene has a complex role as a transcriptional regulator, acting as tumor suppressor or oncogene in different malignancies. The prognostic role of its overexpression has been well-studied in leukemias, especially acute myeloid leukemia (AML), but not in lymphomas. For the first time to our knowledge, we present a study demonstrating the correlation of WT1 expression and survival in various non-Hodgkin lymphomas. We also studied the prognostic implications of WT1 overexpression in adult acute lymphoblastic leukemia (ALL). In our sample of 53 patients— 25 with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), 9 with peripheral T-cell lymphoma (PTCL), 2 with Burkitt’s lymphoma, 2 with mucosa-associated lymphoid tissue (MALT) lymphoma, and 7 with B-cell ALL—, we measured WT1 mRNA from blood samples by quantitative RT-PCR, and divided the patients into subgroups based on the level of expression. Kaplan–Meier survival curves were drawn and compared using the logrank test. In the sample of DLBCL patients, the difference in overall and disease-free survival between WT1-positive and negative subgroups was significant (p=0.0475 and p=0.0004, respectively), and in a few observed cases, a sudden increase in WT1 expression signified a relapse soon followed by death. Disease-free survival curves in MCL and ALL were similarly suggestive of a potential role played by WT1. In PTCL, though WT1-positivity was detected in 4 out of 9 cases, it did not seem to affect survival. The few cases of MALT and Burkitt’s lymphoma all proved to be WT1-negative.
C1 [Ujj, Zsofia] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Buglyo, Gergely] University of Debrecen, Department of Human Genetics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Vargha, Gyorgy] University of Debrecen, Department of Human Genetics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Biro, Sandor] University of Debrecen, Department of Human Genetics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Rejto, Laszlo] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Buglyo, G (reprint author), University of Debrecen, Department of Human Genetics, 4032 Debrecen, Hungary.
EM gbuglyo@hotmail.com
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Tosello V, MansourMR, Barnes K, PaganinM, SulisML, Jenkinson S, Allen CG, Gale RG, Linch DC, Palomero T, Real P,Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G,Wiernik PH, Paietta E, Pieters R,Horstmann M,Meijerink JPP, FerrandoAA(2009)WT1 mutations in T-ALL. Blood 114(5):1038–1045
Heesch S, Goekbuget N, Stroux A, Tanchez JO, Schlee C, Burmeister T, Schwartz S, Blau O, Keilholz U, Busse A, Hoelzer D, Thiel E, Hofmann WK, Baldus CD, 2010, Prognostic implications of mutations and expression of the Wilms tumor 1, WT1, gene in adult acute T-lymphoblastic leukemia. Haematologica 95(6):942–949
Oka Y, Tsuboi A, Oji Y, Kawase I, Sugiyama H, 2008, WT1 peptide vaccine for the treatment of cancer. CurrOpin Immunol 20(2):211–220
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 565
EP 570
DI 10.1007/s12253-013-9729-7
PG 6
ER
PT J
AU Franchi, A
Innocenti, RDD
Palomba, A
Miligi, L
Paiar, F
Franzese, C
Santucci, M
AF Franchi, Alessandro
Innocenti, Rossi Degli Duccio
Palomba, Annarita
Miligi, Lucia
Paiar, Fabiola
Franzese, Ciro
Santucci, Marco
TI Low Prevalence of K-RAS, EGF-R and BRAF Mutations in Sinonasal Adenocarcinomas. Implications for Anti-EGFR Treatments
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sinonasal adenocarcinoma; Intestinal type adenocarcinoma; EGFR; KRAS; BRAF
ID Sinonasal adenocarcinoma; Intestinal type adenocarcinoma; EGFR; KRAS; BRAF
AB We have previously shown that a subset of sinonasal intestinal-type adenocarcinomas (ITAC) shows activation of the epidermal growth factor-receptor (EGFR) pathway. In this study we examine the status of the EGFR, KRAS and BRAF genes in a series of sinonasal intestinal (ITAC) and nonintestinal type adenocarcinomas (non-ITAC). Eighteen ITACs and 12 non-ITACs were studied immunohistochemically for EGFR expression. Point mutations were analyzed for EGFR exons 19 and 21, KRAS exon 2 and BRAF exon 15 by direct sequencing. Non-ITACs showed significantly higher expression of EGFR (p =0.015). Mutation analysis revealed one ITAC with EGFR and one ITAC with KRAS mutation, while two non-ITACs presented mutation of BRAF.We conclude that a subset of sinonasal adenocarcinomas shows overexpression of EGFR, while activating mutations of the signaling cascade downstream of EGFR are rare, suggesting that these tumors could be good candidates for anti-EGFR therapies.
C1 [Franchi, Alessandro] AOU Careggi, Department of Surgery and Translational Medicine, Largo Brambilla 3, 50134 Florence, Italy.
[Innocenti, Rossi Degli Duccio] University of Florence, Department of Clinical and Experimental MedicineFlorence, Italy.
[Palomba, Annarita] Azienda Ospedaliera Universitaria Careggi, Unit of HistopathologyFlorence, Italy.
[Miligi, Lucia] ISPO – Cancer Prevention and Research Institute, Unit of Environmental and Occupational EpidemiologyFlorence, Italy.
[Paiar, Fabiola] Azienda Ospedaliera Universitaria Careggi, Unit of Radiation OncologyFlorence, Italy.
[Franzese, Ciro] Azienda Ospedaliera Universitaria Careggi, Unit of Radiation OncologyFlorence, Italy.
[Santucci, Marco] AOU Careggi, Department of Surgery and Translational Medicine, Largo Brambilla 3, 50134 Florence, Italy.
RP Franchi, A (reprint author), AOU Careggi, Department of Surgery and Translational Medicine, 50134 Florence, Italy.
EM franchi@unifi.it
CR Dulguerov P, Jacobsen MS, Allal AS, Lehmann W, Calcaterra T, 2001, Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review. Cancer 92: 3012–3029
Turner JH, Reh DD, 2012, Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data. Head Neck 34:877–885
Franchi A, Miligi L, Palomba A, Giovannetti L, Santucci M, 2011, Sinonasal carcinomas: recent advances in molecular and phenotypic characterization and their clinical implications. Crit Rev Oncol Hematol 79:265–277
Custodio A, Feliu J, 2013, Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: Beyond KRAS mutations. Crit Rev Oncol Hematol 85:45–81
Franchi A, Fondi C, Paglierani M, Pepi M, Gallo O, Santucci M, 2009, Epidermal growth factor receptor expression and gene copy number in sinonasal intestinal type adenocarcinoma. Oral Oncol 45: 835–838
Franchi A, Palomba A, Massi D, Biancalani M, Sardi I, Gallo O, Santucci M, 2006, Low-grade salivary type tubulo-papillary adenocarcinoma of the sinonasal tract. Histopathology 48:881–884
Garcia-Inclan C, Lopez F, Perez-Escuredo J, Cuesta-Albalad MP, Vivanco B, Centeno I, Balbin M, Suarez C, Llorente JL, Hermsen MA, 2012, EGFR status and KRAS/BRAF mutations in intestinaltype sinonasal adenocarcinomas. Cell Oncol 35:443–450
Szablewski V, Solassol J, Poizat F, LarrieuxM, Crampette L, Mange A, Bascoul-Mollevi C, Costes V, 2013, EGFR expression and KRAS and BRAF mutational status in intestinal-type sinonasal adenocarcinoma. Int J Mol Sci 14:5170–5181
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA, 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139
Taron M, Ichinose Y, Rosell R, Mok T, Massuti B, Zamora L, Mate JL, Manegold C, Ono M, Queralt C, Jahan T, Sanchez JJ, Sanchez- Ronco M, Hsue V, Jablons D, Sanchez JM, Moran T, 2005, Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinoma. Clin Cancer Res 11:5878–5885
Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, LindemanN, Boggon TJ, NaokiK, SasakiH, FujiiY, Eck MJ, Sellers WR, Johnson BE, Meyerson M, 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500
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Yom SS, Rashid A, Rosenthal DI, Elliott DD, Hanna EY,Weber RS, El-Naggar AK, 2005, Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance. Mod Pathol 18:315–319
FrattiniM, Perrone F, Suardi S, Balestra D, Caramuta S, Colombo F, Licitra L, Cantu G, PierottiMA, Pilotti S, 2006, Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Head Neck 28:909–915
Bornholdt J, Hansen J, Steiniche T, Dictor M, Antonsen A,Wolff H, Schlunssen V, Holmila R, Luce D, Vogel U, Husgafvel-Pursiainen K, Wallin H, 2008, K-ras mutations in sinonasal cancers in relation to wood dust exposure. BMC Cancer 8:53
Lopez F, Garcia Inclan C, Perez-Escuredo J, AlvarezMarcos C, Scola B, Suarez C, Llorente JL, Hermsen MA, 2012, KRAS and BRAF mutations in sinonasal cancer. Oral Oncol 48:692–697
Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S,Mazzucchelli L, Frattini M, Siena S, Bardelli A, 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26: 5705–5712
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 571
EP 579
DI 10.1007/s12253-013-9730-1
PG 9
ER
PT J
AU Madaras, L
Kovacs, AK
Szasz, MA
Kenessey, I
Tokes, AM
Szekely, B
Baranyak, Zs
Kiss, O
Dank, M
Kulka, J
AF Madaras, Lilla
Kovacs, Attila Kristof
Szasz, Marcell Attila
Kenessey, Istvan
Tokes, Anna-Maria
Szekely, Borbala
Baranyak, Zsuzsanna
Kiss, Orsolya
Dank, Magdolna
Kulka, Janina
TI Clinicopathological Features and Prognosis of Pregnancy Associated Breast Cancer – A Matched Case Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Breast cancer; Pregnancy associated breast cancer; Pregnancy; Postpartum; Young women
ID Breast cancer; Pregnancy associated breast cancer; Pregnancy; Postpartum; Young women
AB Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women ≤45 years, diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest, Hungary between 1998 and 2012. Histopathology information on tumor type, grade, size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI), associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were recorded, IHC-based subtype was assessed, clinical, management and outcome data were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical management data did not differ in cases and controls. Histopathology of disease at presentation was not significantly different, but NPI assessed the PABC group as having poor, whereas controls as having intermediate prognosis. Associated in situ lesion was more often high grade Extensive Intraductal Carcinoma Component (EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC. Disease-free and overall survival was inferior compared to controls. PABC patients with LuminalB prol and Triple negative tumors had inferior outcomes. On multivariate analysis inferior prognosis of PABC was associated with pregnancy. Our study has demonstrated inferior outcome of PABC. Difference in tumor biology is reflected by the predominance of triple negative and LuminalB tumors in PABC. The strength of the study is the analysis of complete pathology and IHC data.
C1 [Madaras, Lilla] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Kovacs, Attila Kristof] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Szekely, Borbala] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Baranyak, Zsuzsanna] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Kiss, Orsolya] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, 1st Department of Internal Medicine, Tomo u 25-29, 1083 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93., 1091 Budapest, Hungary.
RP Madaras, L (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM lilla.madaras@gmail.com
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Azim HA Jr, Botteri E, Renne G, Dell’Orto P, Rotmensz N, Gentilini O, Sangalli C, Pruneri G, Di Nubila B, Locatelli M, Sotiriou C, Piccart M, Goldhirsch A, Viale G, Peccatori FA, 2012, The biological features and prognosis of breast cancer diagnosed during pregnancy: a case–control study. Acta Oncol 51(5):653–661., DOI 10. 3109/0284186X.2011.636069
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 581
EP 590
DI 10.1007/s12253-013-9735-9
PG 10
ER
PT J
AU Jancsik, AV
Gelencser, G
Maasz, G
Schmidt, J
Molnar, AG
Wittmann, I
Olasz, L
Mark, L
AF Jancsik, A Veronika
Gelencser, Gabor
Maasz, Gabor
Schmidt, Janos
Molnar, A Gergo
Wittmann, Istvan
Olasz, Lajos
Mark, Laszlo
TI Salivary Proteomic Analysis of Diabetic Patients for Possible Oral Squamous Cell Carcinoma Biomarkers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diabetes mellitus; MALDI TOF/TOF mass spectrometry; Oral squamous cell carcinoma; Salivary biomarkers; Type-2 diabetes
ID Diabetes mellitus; MALDI TOF/TOF mass spectrometry; Oral squamous cell carcinoma; Salivary biomarkers; Type-2 diabetes
AB Since oral squamous cell carcinoma (OSCC) is one of the most important causes of death worldwide, the prevention and early detection plays a crucial role. Recent epidemiological studies have incriminated diabetes as a risk factor for the development of OSCC, as well as oral premalignant lesions. As for the last 20 years diabetes and oral squamous cell carcinoma rates have been increasing rapidly, therefore a reliable detection method of major saliva proteins as possible biomarkers for OSCC is of key priority. In this study we collected whole saliva samples from patients with diabetes and from healthy subjects. To reduce the risk of failure and to keep the investigation good reproducible, we proposed an examination and saliva collecting technique. The proteins were analyzed using SDS-PAGE and MALDI TOF/TOF mass spectrometry. Our findings show that the expression of Annexin A8, Peroxiredoxin-2 and Tyrosine kinase is elevated by patients having diabetes. All these proteins have been previously described in cancer saliva samples also in OSCC. Our current findings showed that testing saliva may be an effective and reliable method for detecting oral cancer in early stages.
C1 [Jancsik, A Veronika] University of Pecs, Department of Oral and Maxillofacial Surgery, 5 Dischka G. str, 7620 Pecs, Hungary.
[Gelencser, Gabor] University of Pecs, Department of Oral and Maxillofacial Surgery, 5 Dischka G. str, 7620 Pecs, Hungary.
[Maasz, Gabor] University of Pecs, Institute of Biochemistry and Medical Chemistry, 12 Szigeti str, 7624 Pecs, Hungary.
[Schmidt, Janos] University of Pecs, Institute of Biochemistry and Medical Chemistry, 12 Szigeti str, 7624 Pecs, Hungary.
[Molnar, A Gergo] University of Pecs, 2nd Department of Medicine and Nephrological Center, 1 Pacsirta str, 7624 Pecs, Hungary.
[Wittmann, Istvan] University of Pecs, 2nd Department of Medicine and Nephrological Center, 1 Pacsirta str, 7624 Pecs, Hungary.
[Olasz, Lajos] University of Pecs, Department of Oral and Maxillofacial Surgery, 5 Dischka G. str, 7620 Pecs, Hungary.
[Mark, Laszlo] University of Pecs, Institute of Biochemistry and Medical Chemistry, 12 Szigeti str, 7624 Pecs, Hungary.
RP Mark, L (reprint author), University of Pecs, Institute of Biochemistry and Medical Chemistry, 7624 Pecs, Hungary.
EM laszlo.mark@aok.pte.hu
CR Wong DT, 2006, Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Ass 137:313–321
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Szanto I, Mark L, Bona A, Maasz G, Sandor B, Gelencser G, Turi Z, Gallyas F Jr, 2012, High-throughput screening of saliva for early detection of oral cancer: a pilot study. Technol Cancer Res Treat 11(2):181–188
Jarai T, Maasz G, Burian A, Bona A, Jambor E, Gerlinger I, Mark L, 2012, Mass spectrometry-based salivary proteomics for the discovery of head and neck squamous cell carcinoma. Pathol Oncol Res 18(3):623–628
Parkin DM, Bray F, Ferlay J, Pisani P, 2005, Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 591
EP 595
DI 10.1007/s12253-013-9736-8
PG 5
ER
PT J
AU Forma, E
Wojcik-Krowiranda, K
Jozwiak, P
Szymczyk, A
Bienkiewicz, A
Brys, M
Krzeslak, A
AF Forma, Ewa
Wojcik-Krowiranda, Katarzyna
Jozwiak, Pawel
Szymczyk, Agnieszka
Bienkiewicz, Andrzej
Brys, Magdalena
Krzeslak, Anna
TI Topoisomerase IIβ Binding Protein 1 c.*229C>T (rs115160714) Gene Polymorphism and Endometrial Cancer Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Topoisomerase IIβ binding protein 1; Polymorphism; Genetic variation; Endometrial cancer
ID Topoisomerase IIβ binding protein 1; Polymorphism; Genetic variation; Endometrial cancer
AB TopBP1 (topoisomerase IIβ binding protein 1) protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. In this study we investigated whether alterations in the TopBP1 gene can influence the risk of endometrial cancer. We examined the association between five single nucleotide polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 3′UTR region of the TopBP1 gene and endometrial cancer risk as well as allelespecific gene expression. One hundred twenty-one endometrial cancer patients were genotyped for these SNPs. Allelespecific TopBP1 mRNA and protein expressions were determined by real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with endometrial cancer. Compared to homozygous common allele carriers, heterozygous for the T variant had significantly increased risk of endometrial cancer [adjusted odds ratio (OR)=5.59, 95 % confidence interval (CI): 1.96–15.91, p=0.0003]. Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT genotype. There was a significant association between the rs115160714 and tumor grade and FIGO classification. Most carriers of minor allele had a high grade tumors (G3) classified as FIGO III/IV. The results of our study raise a possibility that a genetic variation of TopBP1 may be implicated in the etiology of endometrial cancer.
C1 [Forma, Ewa] University of Lodz, Department of Cytobiochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Wojcik-Krowiranda, Katarzyna] Medical University of Lodz, Department of Gynecological Oncology, Pabianicka 62, 93-509 Lodz, Poland.
[Jozwiak, Pawel] University of Lodz, Department of Cytobiochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Szymczyk, Agnieszka] University of Lodz, Department of Cytobiochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Bienkiewicz, Andrzej] Medical University of Lodz, Department of Gynecological Oncology, Pabianicka 62, 93-509 Lodz, Poland.
[Brys, Magdalena] University of Lodz, Department of Cytobiochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
[Krzeslak, Anna] University of Lodz, Department of Cytobiochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
RP Krzeslak, A (reprint author), University of Lodz, Department of Cytobiochemistry, 90-236 Lodz, Poland.
EM zreg@biol.uni.lodz.pl
CR Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I, 2005, Endometrial cancer. Lancet 366:491–505
Segev Y, Iqbal J, Lubinski J et al, 2013, Hereditary Breast Cancer Study Group. The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study. Gynecol Oncol., DOI 10.1016/j.ygyno.2013.03.027
Forma E, Brys M, Krajewska W, 2011, TopBP1 in DNA damage response. In: Kruman I, ed, DNA repair/book 4. INTECH Open Access, Rijeka, pp 281–304
Glover JNM, 2006, Insights into the molecular basis of human hereditary breast cancer from studies of the BRCA1 BRCT domain. Fam Cancer 5:89–93
Sokka M, Parkkinen S, Pospiech H, Syvaoja JE, 2010, Function of TopBP1 in genome stability. Subcell Biochem 50:119–141
RodriguezMC, Songyang Z, 2008, BRCT domains: phosphopeptide binding and signaling modules. Front Biosci 13:5905–5915
Smits VA, Warmerdam DO, Martin Y, Freire R, 2010, Mechanisms of ATR-mediated checkpoint signalling. Front Biosci 15:840–853
Forma E, Brzezianska E, Krzeslak A et al, 2012, Association between the c.*229C>T polymorphism of the topoisomerase IIβ binding protein 1, TopBP1, gene and breast cancer. Mol Biol Rep 40:3493–3502
Bilbao C, Ramirez R, Rodriguez G et al, 2010, Double strand break repair components are frequent targets of microsatellite instability in endometrial cancer. Eur J Cancer 46:2821–2827
Zighelboim I, Schmidt AP, Gao F et al, 2009, ATR mutation in endometrioid endometrial cancer is associated with poor clinical outcomes. J Clin Oncol 27:3091–3096
Forma E, Krzeslak A, Bernaciak M, Romanowicz-Makowska H, Brys M, 2012, Expression of TopBP1 in hereditary breast cancer. Mol Biol Rep 39:7795–7804
Liu K, Bellam N, Lin HYet al, 2009, Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer. Mol Cell Biol 29:2673–2693
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 597
EP 602
DI 10.1007/s12253-013-9737-7
PG 6
ER
PT J
AU Feng, L
Tao, L
Dawei, H
Xuliang, L
Xiaodong, L
AF Feng, Liu
Tao, Lin
Dawei, He
Xuliang, Li
Xiaodong, Luo
TI HIF-1α Expression Correlates with Cellular Apoptosis, Angiogenesis and Clinical Prognosis in Rectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hypoxia-inducible factor 1 alpha (HIF-1α); Rectal neoplasm; Apoptosis; Neovascularization
ID Hypoxia-inducible factor 1 alpha (HIF-1α); Rectal neoplasm; Apoptosis; Neovascularization
AB Regional hypoxia caused by accelerated cell proliferation and overgrowth is an important characteristic of neoplasm. Hypoxia can cause a series of changes in gene transcription and protein expression, thereby not only inducing tumor cell resistance to radiotherapy and chemotherapy but also promoting tumor invasion and metastasis. This study aimed to investigate the relationship between HIF-1α expression and cellular apoptosis, angiogenesis and clinical prognosis in rectal carcinoma. In 113 rectal carcinoma cases, cellular apoptosis was analyzed by the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, whereas the levels of HIF-1α expression, VEGF expression, microvessel density (MVD) and lymphatic vessel density(LVD) were examined by immunohistochemical staining. HIF-1 expression was detected in 67 of 113 rectal carcinoma cases (59.3 %). A positive correlation was found among HIF-1α expression, cellular apoptosis and angiogenesis. The 5-year survival rate in the HIF-1α-negative group was significantly higher than that in the HIF-1α- positive group (81.34 % versus 50 %, P<0.05). According to the Cox regression analysis, HIF-1α expression, VEGF expression and cellular apoptosis index were independent risk factors for clinical prognosis in rectal carcinoma. Aberrant HIF-1α expression correlates with apoptosis inhibition, angiogenesis and poor prognosis in rectal carcinoma.
C1 [Feng, Liu] Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), the Children’s Hospital, Chongqing Medical University, Department of Urinary Surgery, 400014 Chongqing, China.
[Tao, Lin] Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), the Children’s Hospital, Chongqing Medical University, Department of Urinary Surgery, 400014 Chongqing, China.
[Dawei, He] Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), the Children’s Hospital, Chongqing Medical University, Department of Urinary Surgery, 400014 Chongqing, China.
[Xuliang, Li] Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), the Children’s Hospital, Chongqing Medical University, Department of Urinary Surgery, 400014 Chongqing, China.
[Xiaodong, Luo] Chongqing Medical University, the Second Affiliated Hospital, Department of Obstetrics and Gynecology, 400010 Chongqing, China.
RP Xiaodong, L (reprint author), Chongqing Medical University, the Second Affiliated Hospital, Department of Obstetrics and Gynecology, 400010 Chongqing, China.
EM cchliuf@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 603
EP 610
DI 10.1007/s12253-013-9738-6
PG 8
ER
PT J
AU Wang, Y
Zheng, T
AF Wang, Yonggang
Zheng, Tianying
TI Screening of Hub Genes and Pathways in Colorectal Cancer with Microarray Technology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Pathway interaction network; Protein-protein interaction networksz analysis; p53 signaling pathway
ID Colorectal cancer; Pathway interaction network; Protein-protein interaction networksz analysis; p53 signaling pathway
AB Here we intend to identify key genes and pathways in the pathogenesis of colorectal cancer (CRC) through analyzing microarray data with bioinformatic tools. The gene expression profile dataset GSE23878 was downloaded from Gene Expression Omnibus and differentially expressed genes (DEGs) were screened out using Student’s t-test. GO function and KEGG pathway enrichment analyses were performed for these DEGs with the DAVID online tool. Interaction network was constructed among the over-represented pathways based on the protein-protein interactions within the pathways. Besides, the protein interaction information obtained from HPRD database were applied to constructed protein-protein interaction networks among the DEGs and hub genes and function module were screened out. A total of 2,296 DEGs were obtained and they were enriched in 34 pathways. An interaction network was constructed among 32 pathways, in which p53 signaling pathway acted as the hub pathway as it showed the highest node degree. The protein-protein interaction network comprised 1,481 interaction relationships among 332 genes which included 40 DEGs. Further analysis revealed that theses DEGs formed 7 functionmodules and many genes, such as PDGFRB, MET, FZD2, CCND1, PRKCB, ARHGEF6, JUP, WNT2, WNT5A and WNT11 were key genes in the networks. The DEGs and disturbed biological functions uncovered in present study may play important roles in the development of CRC and can contribute to the understanding on molecular mechanisms of CRC. Further these DEGs we obtained can be acted as potential biomarkers for diagnosis and therapy of CRC.
C1 [Wang, Yonggang] Shandong University, Cancer Center, Qilu Hospital, Department of Chemotherapy, NO. 107 West Wenhua Road, 250012 Jinan, Shandong Province, China.
[Zheng, Tianying] Shandong University, Cancer Center, Qilu Hospital, Department of Chemotherapy, NO. 107 West Wenhua Road, 250012 Jinan, Shandong Province, China.
RP Zheng, T (reprint author), Shandong University, Cancer Center, Qilu Hospital, Department of Chemotherapy, 250012 Jinan, China.
EM zhentianyingzh@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 611
EP 618
DI 10.1007/s12253-013-9739-5
PG 8
ER
PT J
AU Xuan, Qj
Wang, Jx
Nanding, A
Wang, Zp
Liu, H
Lian, X
Zhang, Qy
AF Xuan, Qi-jia
Wang, Jing-xuan
Nanding, Abiyasi
Wang, Zhi-peng
Liu, Hang
Lian, Xin
Zhang, Qing-yuan
TI Tumor-Associated Macrophages are Correlated with Tamoxifen Resistance in the Postmenopausal Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Tumor-associated macrophages; Epidermal growth factor receptor; Tamoxifen resistance; Obesity
ID Breast cancer; Tumor-associated macrophages; Epidermal growth factor receptor; Tamoxifen resistance; Obesity
AB Tumor-associated macrophages (TAMs) have been correlated with increased angiogenesis and poor prognosis in breast cancer. However, the precise role of TAMs in tamoxifen resistance remains unclear. We used immunohistochemical method to examine the expression of epidermal growth factor receptor (EGFR) and CD163+ macrophages in 100 breast cancer tissues. The clinical and biological features of 100 patients were estrogen receptor (ER)-positive and human epidermal growth factor receptor 2(Her-2)-negative tumors. The tamoxifen resistant tissues (n=48) were the surgical excision samples frompatientswho developed recurrence ormetastasis at the time of adjuvant tamoxifen treatment. The tamoxifen resistant tissues were contrast to tamoxifen sensitive tissues (n=52). Positive staining for EGFR and CD163+ macrophages were observed in 21 samples (43.8 %) and in 26 samples (54.2 %) respectively in tamoxifen resistance group, which were higher than that of tamoxifen sensitive group (P=0.001 and P=0.000279 respectively). Significant positive correlations were found between the expression of EGFR and CD163+ macrophages (r=0.567, P<0.01). CD163+ macrophages were positively correlated with tumor size, lymph node metastasis and obesity. Obesity was also related to tamoxifen resistance (P<0.05). The patients with higher density of CD163+ macrophages infiltration suffered fromshorter time to develop recurrence or metastasis (P<0.05). TAMs may be associated with tamoxifen resistance. Further studies are needed to investigate the potential mechanism between TAMs and tamoxifen resistance.
C1 [Xuan, Qi-jia] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
[Wang, Jing-xuan] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
[Nanding, Abiyasi] Tumor Hospital of Harbin Medical University, Department of Pathology, 150081 Harbin, Heilongjiang, China.
[Wang, Zhi-peng] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
[Liu, Hang] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
[Lian, Xin] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
[Zhang, Qing-yuan] Harbin Medical University, Cancer Hospital, Department of Medical Oncology, Haping Road 150 of Nangang District, 150081 Harbin, Heilongjiang, China.
RP Zhang, Qy (reprint author), Harbin Medical University, Cancer Hospital, Department of Medical Oncology, 150081 Harbin, China.
EM zqyxsci@126.com
CR Key TJ, Verkasalo PK, Banks E, 2001, Epidemiology of breast cancer. Lancet Oncol 2:133–140
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 619
EP 624
DI 10.1007/s12253-013-9740-z
PG 6
ER
PT J
AU Ahmed, AR
Shawky, EAA
Hamed, HR
AF Ahmed, Allah Rehab
Shawky, El-Aty Abd
Hamed, Hamdy Rasha
TI Prognostic Significance of Cyclin D1 and E-cadherin Expression in Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE E-cadherin; CyclinD1; Laryngeal squamous cell carcinoma; Prognosis
ID E-cadherin; CyclinD1; Laryngeal squamous cell carcinoma; Prognosis
AB Cyclin D1 and E-cadherin are important factors in the progression and metastasis of cancers. Their role in laryngeal carcinoma has been studied with conflicting results. To define the frequency of cyclin D1 and E-cadherin expression and its correlation with both the clinicopathological characteristics and prognosis of patients with laryngeal squamous cell carcinoma (LSCC). Tumor tissue samples from 75 patients with laryngeal squamous cell carcinoma were examined for cyclin D1 and E-cadherin expression by immunohistochemistry. The relationship between the expression of both molecules and the age and sex of the patient, tumor site, tumor differentiation, lymph node metastasis, tumor invasiveness, TNM stages, tumor recurrence and overall survival was analyzed. Cyclin D1 was found to be a significant independent prognostic factor of lymph node metastasis (p=0.000). The multivariate analysis revealed that cyclin D1 and E-cadherin expression wasn’t an independent prognostic factor of local recurrence free survival (LRFS) in patients with LSCC (P=0.56 and 0.28) respectively. However, the univariate analysis revealed a significant association between them and LRFS (p=0.003 and 0.000) respectively. Also, the group of high cyclin D1 /low Ecadherin expression had the poorest prognosis, so they might serve as potential predictors of the prognosis of the patients with LSCC. E-cadherin was found to affect the overall survival (OAS) significantly by the univariate analysis (p=0.01). However, by the multivariate analysis the TNM stage was the only independent prognostic factor of OAS (p<0.05). Cyclin D1 can be used as an independent prognostic marker of lymph node metastasis in patients with LSCC and can help to identify those patients with clinically negative lymph nodes but with considerable risk for occult metastasis. Detection of cyclin D1 and E-cadherin status in LSCC may contribute to the identification of patients with high risk factors of local recurrence. However, they don’t appear to be better prognostic predictors than other established markers in LSCC.
C1 [Ahmed, Allah Rehab] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Shawky, El-Aty Abd] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Hamed, Hamdy Rasha] Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine DepartmentMansoura, Egypt.
RP Hamed, HR (reprint author), Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine Department, Mansoura, Egypt.
EM rashahamdy532@yahoo.com
CR Luke CG, Yeoh E, Roder DM, 2008, Exploring trends in laryngeal cancer incidence, mortality and survival: implications for research and cancer control. Asian Pac J Cancer Prev 9(3):397–402
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vanDiest PJ, Michalides RJAM, Jannink I et al, 1997, Cyclin D1 expression in invasive breast cancer: correlations and prognostic value. Am J Pathol 150(2):705–711
Ishikawa T, Furihata M, Ohtsuki Y et al, 1998, Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma. Br J Cancer 77(1):92–97
Wangefjord S, Manjer J, Gaber A et al, 2011, Cyclin D1 expression in colorectal cancer is a favourable prognostic factor inmen but not in women in a prospective, population-based cohort study. Biol Sex Differ 2:10
Ito Y, Matsuura N, Sakon M et al, 1999, Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Hepatology 30(1):90–99
Fracchiolla NS, Pruneri G, Pignataro L et al, 1997, Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: correlation of protein expression with lymph node metastases and advanced clinical stage. Cancer 79(6):1114–1121
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Loddo M, Kingsbury SR, Rashid M et al, 2009, Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer. Br J Cancer 100(6): 959–970
Barnes L, Eveson JW, Reichart PA et al, 2005, World Health Organization classification of tumors: pathology and genetics of tumors of the head and neck. Lyon: IARC. Squamous cell carcinoma in; Hypopharynx, larynx and trachea;, 3): p p121. Edited by Cardesa A, Gale N, Nadal A et al
Edge SB, Byrd DR, Compton CC et al, 2010, Larynx. In: AJCC cancer staging manual, 7th edn. Springer, New York, pp 57–62
Larizadeh MH, Damghani MA, Tabrizchi H et al, 2009, Expression of E-cadherin in squamous cell carcinoma of the larynx and its correlation with clinicopathological features. J Med Sci 9(1):41–45
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Rodrigo JP, Dominguez F, Suarez V et al, 2007, Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer. Arch Otolaryngol 133(2):145–150
Michalides RJAM, van Veelen NMJ, Kristel PMP et al, 1997, Overexpression of cyclin D1 indicates a poor prognosis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 123(5):497–502
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 625
EP 633
DI 10.1007/s12253-014-9741-6
PG 9
ER
PT J
AU Oskina, N
Ermolenko, N
Boyarskih, AU
Lazarev, A
Petrova, V
Ganov, D
Tonacheva, O
Lifschitz, G
Filipenko, M
AF Oskina, А. Natalja
Ermolenko, А. Natalya
Boyarskih, Aleksandrovna Ulyana
Lazarev, F. Aleksandr
Petrova, D. Valentina
Ganov, I. Dmitriy
Tonacheva, G. Olga
Lifschitz, I. Galina
Filipenko, L. Maxim
TI Associations Between SNPs Within Antioxidant Genes and the Risk of Prostate Cancer in the Siberian Region of Russia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GPX1; GSTP1; MnSOD; Prostate cancer; Single nucleotide polymorphisms (SNPs); SOD2
ID GPX1; GSTP1; MnSOD; Prostate cancer; Single nucleotide polymorphisms (SNPs); SOD2
AB In the present study we investigated the association of a number of polymorphic changes in antioxidant system genes (SNPs rs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1 gene and rs4880 in the MnSOD gene) with the risk of prostate cancer. The association of disease stage and PSA levels with specific genotypes was also analyzed. A study was conducted with the participation of 736 Russian men. We compared the frequency of occurrence of the studied alleles in patients with prostate cancer (392) to a control group (344) of men without a history of cancer. Genotyping was performed by real-time PCR. Comparison of frequencies of alleles and genotypes were performed using logistic regression analysis. No statistically significant association with the risk of prostate cancer was found for any of the SNPs studied (p>0.05). For SNP rs1695 in the GSTP1 gene, a correlation with cancer disease stage was observed: a GG genotype is significantly more common in patients with PCa in the 3rd and 4th stage than 1st and 2nd (OR[95%CI]= 2.66[1.15–6.18], p=0.02). Both studied SNPs of GSTP1 gene are associated with the level of PSA: the GG rs1695 and the TT rs1138272 genotypes are associated with higher PSA levels (p=1.5*10−3).
C1 [Oskina, А. Natalja] Institute of Chemical Biology and Fundamental MedicineNovosibirsk, Russian Federation.
[Ermolenko, А. Natalya] Institute of Chemical Biology and Fundamental MedicineNovosibirsk, Russian Federation.
[Boyarskih, Aleksandrovna Ulyana] Institute of Chemical Biology and Fundamental MedicineNovosibirsk, Russian Federation.
[Lazarev, F. Aleksandr] N. N. Blokhin Russian Cancer Research Center RAMSBarnaul, Russian Federation.
[Petrova, D. Valentina] N. N. Blokhin Russian Cancer Research Center RAMSBarnaul, Russian Federation.
[Ganov, I. Dmitriy] N. N. Blokhin Russian Cancer Research Center RAMSBarnaul, Russian Federation.
[Tonacheva, G. Olga] Krasnoyarsk Regional Oncology CenterKrasnoyarsk, Russian Federation.
[Lifschitz, I. Galina] Institute of Chemical Biology and Fundamental MedicineNovosibirsk, Russian Federation.
[Filipenko, L. Maxim] Institute of Chemical Biology and Fundamental MedicineNovosibirsk, Russian Federation.
RP Oskina, N (reprint author), Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russian Federation.
EM nattasha.o@gmail.com
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Yossepowitch O, Pinchuk I, Gur U, Neumann A, Lichtenberg D, Baniel J, 2007, Advanced but not localized prostate cancer is associated with increased oxidative stress. J Urol 178(4 Pt 1):1238–1243, discussion 1243-1234
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 635
EP 640
DI 10.1007/s12253-014-9742-5
PG 6
ER
PT J
AU Yang, X
Liu, G
Xiao, H
Yu, F
Xiang, X
Lu, Y
Li, W
Liu, X
Li, Sh
Shi, Y
AF Yang, Xiaolin
Liu, Geling
Xiao, Hongzhen
Yu, Fang
Xiang, Xiuxiu
Lu, Yifang
Li, Weijuan
Liu, Xiuling
Li, Sha
Shi, Yanping
TI TPX2 Overexpression in Medullary Thyroid Carcinoma Mediates TT Cell Proliferation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medullary thyroid cancer; TPX2; siRNA; Proliferation; Apoptosis
ID Medullary thyroid cancer; TPX2; siRNA; Proliferation; Apoptosis
AB TPX2 (targeting protein for xenopus kinesinlike protein 2), a microtubule-associated protein, plays an important role in the formation of the mitotic spindle. Abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for medullary thyroid cancer (MTC). We investigated the expression of TPX2 in human MTC tissues and its potential use as a therapeutic target. Immunohistochemical analysis of TPX2 expression was performed for 32 cases of MTC and 8 cases of normal thyroid. TPX2 expression was found to be significantly higher in MTC compared to normal thyroid tissues (P<0.05), and to be associated with tumor size, lymph node metastasis, and advanced disease stage. The cellular effects of TPX2 knockdown, including cell proliferation, apoptosis, cell cycle diffusions, and mitotic gene expression were investigated using small interfering RNA (siRNA). TPX2- siRNA caused G1 and G2-phase cell cycle arrest, inhibited cell proliferation, and induced apoptosis. TPX2-siRNA also downregulated Aurora-A and cyclinB1 protein expression in MTC cells and enhanced the expression of p53 protein (P<0.05). These results suggest that TPX2 may be of potential use as a new marker for MTC prognosis and therapy.
C1 [Yang, Xiaolin] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Liu, Geling] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Xiao, Hongzhen] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Yu, Fang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Xiang, Xiuxiu] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Lu, Yifang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Weijuan] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Liu, Xiuling] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Sha] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Shi, Yanping] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
RP Liu, G (reprint author), Tangshan Workers Hospital, Department of Endocrinology (Section I), Tangshan, China.
EM liugeling1963@163.com
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Moore JD, 2013, In the wrong place at the wrong time: does cyclin mislocalization drive oncogenic transformation? Nat Rev Cancer 13(3):201–208
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 641
EP 648
DI 10.1007/s12253-014-9743-4
PG 8
ER
PT J
AU Posfai,
Irsai, G
Illes,
Mehes, G
Marton, I
Molnar, Cs
Csipo, I
Barath, S
Gergely, L
AF Posfai, Eva
Irsai, Gabor
Illes, Arpad
Mehes, Gabor
Marton, Imelda
Molnar, Csaba
Csipo, Istvan
Barath, Sandor
Gergely, Lajos
TI Evaluation of Significance of Lymphocyte Subpopulations and Non-specific Serologic Markers in B-cell Non-Hodgkin’s Lymphoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lymphocyte subpopulations; Non-specific serologicmarkers; Non-Hodgkin’s lymphoma; Immuno-chemotherapy; Host immune system
ID Lymphocyte subpopulations; Non-specific serologicmarkers; Non-Hodgkin’s lymphoma; Immuno-chemotherapy; Host immune system
AB The use of rituximab brought attention to the hosts’ immune system and to the microenvironment in non- Hodgkin’s lymphoma cases. Our aim was to identify prognostic factors that can be measured easily to indicate the current state of the patient’s immune status and possible reaction against malignant cells. In the retrospective analysis (2000–2008), 66 patients diagnosed with B-cell non- Hodgkin’s lymphomas were enrolled (40 women, 26 men; mean age: 51 years).White blood cells, lymphocytes, CD3 +; CD4 +; CD8+T-cells, immunoglobulin types A; G; M, anticardiolipin antibody isotypes A; G; M; and levels of beta-2- microglobulin were measured before the initiation of the first cycle of chemotherapy, during and after 4-weeks treatment. As for CD 3+ T-lymphocytes, the absolute CD 3+ T – lymphocyte numbers were higher before (0.78×109/L) versus during (0.27×109/L) treatment, and increased percentages were detected in pre- (66.57 %) and post-treatment (75.32 %). Absolute numbers of CD 8+ T-lymphocyte levels showed reduction before (0.26×109/L) versus during (0.10× 109/L) therapy, but were elevated after (0.28×109/L) treatment, while increased percentage before (21.99 %) versus after (29.85 %), and during (24.56 %) versus after (29.85 %) therapy were seen. Average white blood cell numbers were increased before (9.71×109/L) versus during (12.07×109/L) treatment, while decreased numbers could be observed, after (5.47×109/L) treatment. IgA levels were decreased before (2.51 g/L) versus after (1.63 g/L) therapy. IgG levels were higher before (12.25 g/L) vs. after (8.64 g/L) treatment. IgM levels were decreased before (1.76 g/L) and after (0.83 g/L) as well as before (1.76 g/L) versus during (0.73 g/L) treatment. Anti-cardiolipin antibody type A level were decreased before (2.76 U/ml) versus after (2.49 U/ml) treatment. Decreased level of beta-2-microglobulin could be observed before (2.91 mg/L) versus post (2.28 mg/L) chemotherapy. Findings may provide better insight into the effects of immuno-chemotherapy on the hosts’ immune system.
C1 [Posfai, Eva] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Irsai, Gabor] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Marton, Imelda] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Molnar, Csaba] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Csipo, Istvan] University of Debrecen, Medical and Health Science Center, Regional Laboratory for ImmunologyDebrecen, Hungary.
[Barath, Sandor] University of Debrecen, Medical and Health Science Center, Regional Laboratory for ImmunologyDebrecen, Hungary.
[Gergely, Lajos] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Gergely, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM lgergely@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 649
EP 654
DI 10.1007/s12253-014-9744-3
PG 6
ER
PT J
AU Gu, JM
Jang, IB
AF Gu, Jin Mi
Jang, Ik Byung
TI Clinicopathologic Significance of Sox2, CD44 and CD44v6 Expression in Intrahepatic Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intrahepatic cholangiocarcinoma; Sox2; CD44; CD44v6; Survival
ID Intrahepatic cholangiocarcinoma; Sox2; CD44; CD44v6; Survival
AB Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p=0.025), T4 stage (p= 0.046), and worse overall survival (p=0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p>0.05). CD44 expression showed an association with periductal infiltrative type (p=0.034), poor differentiation (p=0.012), and vascular invasion (p=0.009). CD44v6 expression was evident in patients with stage IV (p=0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC.
C1 [Gu, Jin Mi] Yeungnam University, College of Medicine, Department of Pathology, 170, Hyeonchung-ro, Nam-guDaegu, South Korea.
[Jang, Ik Byung] Yeungnam University, College of Medicine, Department of Internal MedicineDaegu, South Korea.
RP Gu, JM (reprint author), Yeungnam University, College of Medicine, Department of Pathology, Daegu, South Korea.
EM mjgu@yu.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 655
EP 660
DI 10.1007/s12253-014-9745-2
PG 6
ER
PT J
AU Zhang, ShL
Yuan, F
Guan, X
Li, J
Liu, LX
Sun, J
Liu, B
Ma, W
Deng, MF
AF Zhang, Shun Lu
Yuan, Fang
Guan, Xuan
Li, Juan
Liu, Lian Xin
Sun, Jing
Liu, Bo
Ma, Wei
Deng, Mei Feng
TI Association of Genetic Polymorphisms in HSD17B1, HSD17B2 and SHBG Genes with Hepatocellular Carcinoma Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SHBG; HSD17B1; HSD17B2; HCC
ID SHBG; HSD17B1; HSD17B2; HCC
AB Genetic polymorphisms of enzymes involved in estrogen synthesizing/transporting can influence the risk of hormone-dependent diseases. The incidence rate and relative risk for hepatocellular carcinoma (HCC) are higher in men than in women. This study was conducted to explore the relationship of single nucleotide polymorphisms (SNPs) in 17 β-Hydroxysteroid dehydrogenases (HSD17B1 and HSD17B2) and sex hormone-binding globulin (SHBG) genes with the risk of HCC within Chinese Han population. Polymorphisms of HSD17B1 rs676387, HSD17B2 rs8191246 and SHBG rs6259 were genotyped in 253 HCC patients and 438 healthy control subjects using the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Significantly increased HCC risk was found to be associated with T allele of rs676387 and G allele of rs8191246. Increased HCC risks were found in different genetic model (TT genotype in a recessive model, T allele carriers in a dominant model, TT genotype and TG genotype in a codominant model for HSD17B1 rs676387, G allele carriers in a dominant model and AG genotype in a codominant model for HSD17B2 rs8191246, respectively). No association between SHBG rs6259 and HCC risk was observed. The present study provided evidence that HSD17B1 rs676387 and HSD17B2 rs8191246 were association with HCC development. Further studies in diverse ethnic population with larger sample size were recommended to confirm the findings.
C1 [Zhang, Shun Lu] Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
[Yuan, Fang] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Immunology, 610041 Chengdu, China.
[Guan, Xuan] Chengdu Medical College, Department of Experimental Technology, 610500 Chengdu, China.
[Li, Juan] Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
[Liu, Lian Xin] Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
[Sun, Jing] Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
[Liu, Bo] Cheng Du Medical College, Department of Lab Medicine, 610500 Chengdu, China.
[Ma, Wei] Cheng Du Medical College, Department of Lab Medicine, 610500 Chengdu, China.
[Deng, Mei Feng] Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
RP Zhang, ShL (reprint author), Cheng Du Medical College, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
EM zhangls2012@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 661
EP 666
DI 10.1007/s12253-014-9746-1
PG 6
ER
PT J
AU Shin, E
Yu, YD
Kim, DS
Won, HN
AF Shin, Eun
Yu, Young-Dong
Kim, Dong-Sik
Won, Hee Nam
TI Adiponectin Receptor Expression Predicts Favorable Prognosis in Cases of Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Adiponectin; Immunohistochemistry; Prognosis
ID Hepatocellular carcinoma; Adiponectin; Immunohistochemistry; Prognosis
AB Obesity influences risk, progression and prognosis of various cancers including hepatocellular carcinoma (HCC). Adipose-tissue-derived adipokines has been considered to be involved in tumorigenesis and adiponecin, one such adipokine, has antiproliferative effect on obesity-related malignancies, though variable signal pathway mediated by adiponectin receptors-AdipoR1 and AdipoR2. In this study, we investigated expression of adiponectin and adiponectin receptors in tumor and non-tumorous hepatic tissues of HCC patients and its clinicopathological significance. We collected 75 HCC tissues and 70 non-tumorous hepatic tissues from HCC patients who underwent surgical resection. The tissue microarrays were constructed and immunohistochemical study for adiponectin, AdipoR1 and AipoR2 was performed. Adiponectin and AdipoR1 expression rates were significantly lower in HCC than non-neoplastic hepatic tissues (82.7 % vs. 97.1 % and 24.0 % vs. 90 %, P=0.005 and <0.001, respectively). Immunopositivity for adiponectin was associated with small tumor size, low Edmonson-Steiner grade and absence of other organ invasion (P=0.015, 0.021 and 0.028, respectively). AdipoR1 expression had association with absence of vascular invasion (P=0.028) and AdipoR2 expression was correlated with lower histologic grade and low pathologic Tstage (P=0.003 and 0.008, respectively). Cox regression analysis revealed that low expression of AdipoR1 and AdipoR2 were associated with increased risk of recurrence and death, respectively (hazard ration = 3.222 and 14.797, respectively). These findings suggest that loss of adiponectin, and adiponectin receptors expression is associated with aggressive clinicopathological features of HCC and AdipoR1 and AdipoR2 might serve as the independent prognostic factors for HCC patients.
C1 [Shin, Eun] Seoul National University Bundang Hospital, Department of Pathology, 173-82 Gumiro, Bundang-gu, Seongnam, 463-707 Gyeonggi, South Korea.
[Yu, Young-Dong] Korea University, College of Medicine, Department of Surgery, 126-1 Anam-dong 5 ga, Seongbuk-gu, 163-705 Seoul, South Korea.
[Kim, Dong-Sik] Korea University, College of Medicine, Department of Surgery, 126-1 Anam-dong 5 ga, Seongbuk-gu, 163-705 Seoul, South Korea.
[Won, Hee Nam] Korea University, College of Medicine, Department of Pathology, 126-1 Anam-dong 5 ga, Seongbuk-gu, 163-705 Seoul, South Korea.
RP Won, HN (reprint author), Korea University, College of Medicine, Department of Pathology, 163-705 Seoul, South Korea.
EM nhw@korea.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 667
EP 675
DI 10.1007/s12253-014-9747-0
PG 9
ER
PT J
AU Sukosd, F
Ivanyi, B
Pajor, L
AF Sukosd, Farkas
Ivanyi, Bela
Pajor, Laszlo
TI Accurate Determination of the Pathological Stage with Gross Dissection Protocol for Radical Cystectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer stage; Gross dissection; Pathology report; Radical cystectomy; Total embedding; Urinary bladder carcinoma; Whole mount section
ID Cancer stage; Gross dissection; Pathology report; Radical cystectomy; Total embedding; Urinary bladder carcinoma; Whole mount section
AB The current protocol for reporting urinary bladder cancer in radical cystectomies may exhibit limitations in the diagnostic accuracy, such as a risk of understaging, especially in cases with prostatic involvement. Difficulty can arise in the verification of stage pT0, and the assessment of surgical margins is suboptimal. We have developed a daily gross dissection protocol practice where radical cystectomies are totally embedded and evaluated histologically in wholemount sections. We report here on the first 138 consecutive specimens from 2008 to the first quarter of 2012 inclusive. The incidence of the cancer stages was compared with data on 15,586 radical cystectomies from the literature. The differences were analyzed with the one-sample z-test (p<0.05). The following emerged from and our series and the literature data: pT0 8.7 % and 6.1 %; pTa 0.7 % and 2.9 %; pTis 2.9 % and 6 %; pT1 15.2 % and 15.5 %; pT2 21 % and 23.3 %; pT3 34.8 % and 34.3 %; and pT4 16.7 % and 11 %, respectively. Our findings closely reflected the means of the published statistical data based on a large number of cases. The differences were due to the more detailed processing: the case numbers in groups from pTis to pT2 were comparatively low, while those in groups pT3 and pT4 were higher. The difference in group pT4 was significant (p=0.0494).With this method, only those samples were regarded as pT0 in which the granulomatous area and the hemosiderin deposition indicative of the earlier intervention were observable and the entire preparation was tumor-free.
C1 [Sukosd, Farkas] University of Szeged, Department of Pathology, 2 Allomas u, 6720 Szeged, Hungary.
[Ivanyi, Bela] University of Szeged, Department of Pathology, 2 Allomas u, 6720 Szeged, Hungary.
[Pajor, Laszlo] University of Szeged, Department of Urology, 57 Kalvaria u, 6725 Szeged, Hungary.
RP Sukosd, F (reprint author), University of Szeged, Department of Pathology, 6720 Szeged, Hungary.
EM sukosd.farkas@med.u-szeged.hu
CR Parkin DM, 2008, The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl, 218)42:12–20
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Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S et al, 2001, Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19:666–675
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Lopez-Beltran A, Bassi PF, Pavone-Macaluso M, Montironi R, 2004, Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis. A joint proposal of the European Society of Uropathology and the Uropathology Working Group. Virchows Arch 445:103–110
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 677
EP 685
DI 10.1007/s12253-014-9748-z
PG 9
ER
PT J
AU Novak Kujundzic, R
Grbesa, I
Ivkic, M
Kruslin, B
Konjevoda, P
Gall Troselj, K
AF Novak Kujundzic, Renata
Grbesa, Ivana
Ivkic, Mirko
Kruslin, Bozo
Konjevoda, Pasko
Gall Troselj, Koraljka
TI Possible Prognostic Value of BORIS Transcript Variants Ratio in Laryngeal Squamous Cell Carcinomas – a Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laryngeal squamous cell carcinoma; Prognostic value; BORIS; Transcript variant; Immunohistochemistry; RT-PCR
ID Laryngeal squamous cell carcinoma; Prognostic value; BORIS; Transcript variant; Immunohistochemistry; RT-PCR
AB BORIS is a paralog of a highly conserved, multifunctional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent nontumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7−) as an independent prognostic factor associated with disease relapse during a 5-year followup period. Patients having BORIS 7+/BORIS 7− ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/ BORIS 7− ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival.
C1 [Novak Kujundzic, Renata] Ruder Boskovic Institute, Laboratory for Epigenomics, Bijenicka cesta 54, 10002 Zagreb, Croatia.
[Grbesa, Ivana] Ruder Boskovic Institute, Laboratory for Epigenomics, Bijenicka cesta 54, 10002 Zagreb, Croatia.
[Ivkic, Mirko] Sestre Milosrdnice University Hospital, Department of Otorhinolaryngology and Head and Neck Surgery, 10000 Zagreb, Croatia.
[Kruslin, Bozo] University Hospital Sisters of Charity, Ljudevit Jurak Department of Pathology, 10000 Zagreb, Croatia.
[Konjevoda, Pasko] Ruder Boskovic Institute, Center for NMR, Bijenicka cesta 54, 10002 Zagreb, Croatia.
[Gall Troselj, Koraljka] Ruder Boskovic Institute, Laboratory for Epigenomics, Bijenicka cesta 54, 10002 Zagreb, Croatia.
RP Novak Kujundzic, R (reprint author), Ruder Boskovic Institute, Laboratory for Epigenomics, 10002 Zagreb, Croatia.
EM rnovak@irb.hr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 687
EP 695
DI 10.1007/s12253-014-9749-y
PG 9
ER
PT J
AU Kwon, YS
Lee, JH
Kim, B
Park, JW
Kwon, KT
Kang, HS
Kim, Sh
AF Kwon, Young Sun
Lee, Jae-Ho
Kim, Bora
Park, Jong-Wook
Kwon, Kyu Taeg
Kang, Hee Sun
Kim, Shin
TI Complexity in Regulation of microRNA Machinery Components in Invasive Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNA biogenesis; DGCR8; AGO2; Ki-67; Invasive breast carcinoma
ID microRNA biogenesis; DGCR8; AGO2; Ki-67; Invasive breast carcinoma
AB Altered expression of microRNA (miRNA) machinery components may play an important role in breast cancer progression. The objective of the current study was to evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to assess the value of clinical parameters on their expression. By using quantitative real-time PCR, we examined the expression of the four miRNA machinery components in 52 breast tumor tissues which are diagnosed as invasive ductal carcinoma and adjacent non-neoplastic tissues. In the present study, decreased mRNA expression levels of major miRNA machinery components were observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are positively correlated with to each other. This study revealed for the first time that expression alterations of DGCR8 are significantly associated with estrogen receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was significantly correlated with N stage. These results provided evidences that downregulated the four miRNA machinery components may play an important role in breast pathobiology and that DGCR8 and AGO2 might be associated with important clinical factors.
C1 [Kwon, Young Sun] Keimyung University, School of Medicine, Department of Pathology, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Lee, Jae-Ho] Keimyung University, School of Medicine, Department of Anatomy, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Kim, Bora] Keimyung University, School of Medicine, Department of Immunology, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Park, Jong-Wook] Keimyung University, School of Medicine, Department of Immunology, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Kwon, Kyu Taeg] Keimyung University, School of Medicine, Department of Immunology, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Kang, Hee Sun] Keimyung University, School of Medicine, Department of General Surgery, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
[Kim, Shin] Keimyung University, School of Medicine, Department of Immunology, 1095 Dalgubeoldaero, Dalseo-Gu, 704-701 Daegu, South Korea.
RP Kim, Sh (reprint author), Keimyung University, School of Medicine, Department of Immunology, 704-701 Daegu, South Korea.
EM god98005@dsmc.or.kr
CR Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF, Macmillan D, Blamey RW, Ellis IO, 2005, High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340–350., DOI 10.1002/ijc.21004
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM, 2004, Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374., DOI 10.1158/1078-0432.CCR-04-0220
Perou CM, Sorlie T, EisenMB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen- Dale AL, Brown PO, BotsteinD(2000)Molecular portraits of human breast tumours. Nature 406(6797):747–752., DOI 10.1038/35021093
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 697
EP 705
DI 10.1007/s12253-014-9750-5
PG 9
ER
PT J
AU Kropotova, SE
Zinovieva, LO
Zyryanova, FA
Dybovaya, IV
Prasolov, SV
Beresten, FS
Oparina, YN
Mashkova, DT
AF Kropotova, S Ekaterina
Zinovieva, L Olga
Zyryanova, F Alisa
Dybovaya, I Vera
Prasolov, S Vladimir
Beresten, F Sergey
Oparina, Yu Nina
Mashkova, D Tamara
TI Altered Expression of Multiple Genes Involved in Retinoic Acid Biosynthesis in Human Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Retinoic acid biosynthesis; Gene expression; Tumor progression
ID Colorectal cancer; Retinoic acid biosynthesis; Gene expression; Tumor progression
AB All-trans-retinoic acid (atRA), the oxidized form of vitamin A (retinol), regulates a wide variety of biological processes, such as cell proliferation and differentiation. Multiple alcohol, retinol and retinaldehyde dehydrogenases (ADHs, RDHs, RALDHs) as well as aldo-keto reductases (AKRs) catalyze atRA production. The reduced atRA biosynthesis has been observed in several human tumors, including colorectal cancer. However, subsets of atRA-synthesizing enzymes have not been determined in colorectal tumors. We investigated the expression patterns of genes involved in atRA biosynthesis in normal human colorectal tissues, primary carcinomas and cancer cell lines by RT-PCR. These genes were identified using transcriptomic data analysis (expressed sequence tags, RNA-sequencing, microarrays). Our results indicate that each step of the atRA biosynthesis pathway is dysregulated in colorectal cancer. Frequent and significant decreases in the mRNA levels of the ADH1B, ADH1C, RDHL, RDH5 and AKR1B10 genes were observed in a majority of colorectal carcinomas. The expression levels of the RALDH1 gene were reduced, and the expression levels of the cytochrome CYP26A1 gene increased. The human colon cancer cell lines showed a similar pattern of changes in the mRNA levels of these genes. A dramatic reduction in the expression of genes encoding the predominant retinoloxidizing enzymes could impair atRA production. The most abundant of these genes, ADH1B and ADH1C, display decreased expression during progression from adenoma to early and more advanced stage of colorectal carcinomas. The diminished atRA biosynthesis may lead to alteration of cell growth and differentiation in the colon and rectum, thus contributing to the progression of colorectal cancer.
C1 [Kropotova, S Ekaterina] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Zinovieva, L Olga] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Zyryanova, F Alisa] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Dybovaya, I Vera] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Prasolov, S Vladimir] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Beresten, F Sergey] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Oparina, Yu Nina] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
[Mashkova, D Tamara] Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
RP Mashkova, DT (reprint author), Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
EM tamashkova@yandex.ru
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 707
EP 717
DI 10.1007/s12253-014-9751-4
PG 11
ER
PT J
AU Oberlander, M
Alkemade, H
Bunger, S
Ernst, F
Thorns, Ch
Braunschweig, T
Habermann, J
AF Oberlander, Martina
Alkemade, Hendrik
Bunger, Stefanie
Ernst, Floris
Thorns, Christoph
Braunschweig, Till
Habermann, K. Jens
TI A ‘Waterfall’ Transfer-based Workflow for Improved Quality of Tissue Microarray Construction and Processing in Breast Cancer Research
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tissue microarray (TMA); Biomarkers; High-throughput technique; Immunohistochemistry; Immunofluorescence staining
ID Tissue microarray (TMA); Biomarkers; High-throughput technique; Immunohistochemistry; Immunofluorescence staining
AB A major focus in cancer research is the identification of biomarkers for early diagnosis, therapy prediction and prognosis. Hereby, validation of target proteins on clinical samples is of high importance. Tissue microarrays (TMAs) represent an essential advancement for high-throughput analysis by assembling large numbers of tissue cores with high efficacy and comparability. However, limitations along TMA construction and processing exist. In our presented study, we had to overcome several obstacles in the construction and processing of high-density breast cancer TMAs to ensure good quality sections for further research. Exemplarily, 406 breast tissue cores from formalin-fixed and paraffin embedded samples of 245 patients were placed onto three recipient paraffin blocks. Sectioning was performed using a rotary microtome with a "waterfall" automated transfer system. Sections were stained by immunohistochemistry and immunofluorescence for nine proteins. The number and quality of cores after sectioning and staining was counted manually for each marker. In total, 97.1 % of all cores were available after sectioning, while further 96 % of the remaining cores were evaluable after staining. Thereby, normal tissue cores were more often lost compared to tumor tissue cores. Our workflow provides a robust method for manufacturing high-density breast cancer TMAs for subsequent IHC or IF staining without significant sample loss.
C1 [Oberlander, Martina] University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
[Alkemade, Hendrik] University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
[Bunger, Stefanie] University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
[Ernst, Floris] University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
[Thorns, Christoph] University of Schleswig-Holstein, Institute of Pathology, Campus LubeckLubeck, Germany.
[Braunschweig, Till] Medical Faculty of the Technical University of Aachen, Department of Pathology, Pauwelsstraße 30, 52074 Aachen, Germany.
[Habermann, K. Jens] University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
RP Habermann, J (reprint author), University of Lubeck and University Medical Center Schleswig-Holstein, Department of Surgery, Section for Translational Surgical Oncology and Biobanking, 23538 Lubeck, Germany.
EM habermann@biobank.uni-luebeck.de
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 719
EP 726
DI 10.1007/s12253-014-9752-3
PG 8
ER
PT J
AU Lang, D
Marwitz, S
Heilenkotter, U
Schumm, W
Behrens, O
Simon, R
Reck, M
Vollmer, E
Goldmann, T
AF Lang, S. Dagmar
Marwitz, Sebastian
Heilenkotter, Uwe
Schumm, W
Behrens, Oliver
Simon, Ronald
Reck, Martin
Vollmer, Ekkehard
Goldmann, Torsten
TI Transforming Growth Factor-Beta Signaling Leads to uPA/PAI-1 Activation and Metastasis: A Study on Human Breast Cancer Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastasis; Breast cancer; Urokinase-type plasminogen activator; Plasminogen activator inhibitor-1; Transforming growth factor beta; Mothers against decapentaplegic homolog 3; BMP Activin membrane-bound inhibitor homolog
ID Metastasis; Breast cancer; Urokinase-type plasminogen activator; Plasminogen activator inhibitor-1; Transforming growth factor beta; Mothers against decapentaplegic homolog 3; BMP Activin membrane-bound inhibitor homolog
AB Metastasis represents a major problem in the treatment of patients with advanced primary breast cancer. Both Transforming Growth Factor-Beta (TGF-β) signaling and Plasminogen Activator (PA) components, urokinasetype Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) represent a complex network crucial for such enhanced invasiveness of tumors and imply high prognostic/predictive and promising therapeutic potential. Therefore, protein expression of specific effector molecules comprising the main parts of the TGF-β signaling pathway were determined in HOPE-fixed human tumor tissues through IHC (Scoring) using tissue microarray (TMA) technique and correlated with respective uPA and PAI-1 levels determined earlier in the same TMAs through optimized IHC and semi-quantitative image analysis. TGF-β signaling was active in vast majority (96 %) of the tumor samples and 88 % of all cases were significantly correlated with established metastasis markers uPA and PAI-1. In addition, TGF-β was also closely associated with tumor size, nodal status and two steroid hormone receptors. Consistent interrelationships between TGF-β, PA components and additional tumor characteristics underline the superiority of such more comprising data with regards to confirming TGF-β signaling as a promising target system to inhibit metastasis in advanced breast cancer.
C1 [Lang, S. Dagmar] Research Center Borstel, Clinical and Experimental Pathology, Parkallee 3a, 23845 Borstel, Germany.
[Marwitz, Sebastian] Research Center Borstel, Clinical and Experimental Pathology, Parkallee 3a, 23845 Borstel, Germany.
[Heilenkotter, Uwe] Holsteinisches Breast Center, Gynecological Hospital, Clinical Center ItzehoeItzehoe, Germany.
[Schumm, W] Holsteinisches Breast Center, imland Clinic Rendsburg, PathologyRendsburg, Germany.
[Behrens, Oliver] Holsteinisches Breast Center, imland Clinic RendsburgRendsburg, Germany.
[Simon, Ronald] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Reck, Martin] Airway Research Center North (ARCN)- Member of the German Center for Lung Research (DZL)Borstel, Germany.
[Vollmer, Ekkehard] Research Center Borstel, Clinical and Experimental Pathology, Parkallee 3a, 23845 Borstel, Germany.
[Goldmann, Torsten] Research Center Borstel, Clinical and Experimental Pathology, Parkallee 3a, 23845 Borstel, Germany.
RP Lang, D (reprint author), Research Center Borstel, Clinical and Experimental Pathology, 23845 Borstel, Germany.
EM dlang@fz-borstel.de
CR Welch DR, Steeg PS, Rinker-Schaeffer CW, 2000, Molecular biology of breast cancer metastasis. Genetic regulation of human breast carcinoma metastasis. Breast Cancer Res 2:408–412
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Huang SS, Ling T-Y, Tseng W-F, Huang Y-W, Tang F-M, Leal SM, Huang JS, 2003, FASEB J 17:2068–2080
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Matise LA, Palmer TD, Ashby WJ, Nashabi A, Chytil A, Aakre M, Pickup MW, Gorska AE, Zijlstra A, Moses HL, 2012, Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Breast Cancer Res 14: R98
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 727
EP 732
DI 10.1007/s12253-014-9753-2
PG 6
ER
PT J
AU Liu, G
Xie, B
Gong, L
Zhou, J
Shu, G
AF Liu, Ganglei
Xie, Biao
Gong, Lin
Zhou, Jianping
Shu, Guoshun
TI The Expression of p66Shc Protein in Benign, Premalignant, and Malignant Gastrointestinal Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Colorectal cancer; p66Shc; Neoplasia; Hyperplastic polyps; Immunohistochemistry
ID Gastric cancer; Colorectal cancer; p66Shc; Neoplasia; Hyperplastic polyps; Immunohistochemistry
AB ROS produced from Oxidative stress have long been recognized to be involved in carcinogenesis. p66Shc generates H2O2 by oxidizing cytochrome c, and its expression has been reported to be elevated in several tumors. However, the expression of p66Shc in gastric cancer has not been reported, and its role in colorectal cancer has not been well elucidated. This study investigated p66Shc expression in benign, premalignant, and malignant gastric and colorectal lesions. p66Shc expression in 146 gastric tumors, 136 colorectal tumors, 45 gastric hyperplastic polyps, 33 gastric low-grade intraepithelial neoplasias, 41 gastric high-grade intraepithelial neoplasias, 42 colorectal hyperplastic polyps, 21 colorectal low-grade intraepithelial neoplasias, 38 colorectal high-grade intraepithelial neoplasias, and 30 normal gastric and colorectal tissues was measured by immunohistochemistry. Most normal gastric and colorectal tissues exhibited low or no p66Shc expression (93.4 %), while most gastric and colorectal tumors exhibited moderate to high p66Shc expression (78.1 %– 80.9 %). The p66Shc expression in normal gastric and colorectal tissues were significantly lower than that in the lowgrade intraepithelial neoplasias (p<0.05), high-grade intraepithelial neoplasias (p<0.01), and gastric adenocarcinomas (p<0.01 or <0.001). No differences in p66Shc expression were observed in gastric and colorectal hyperplastic polyps compared to the normal tissues. No statistically significant differences in p66Shc expression were observed between patients with different disease stages, different tumor grades, and with or without lymph node metastasis in gastric and colorectal cancers. In conclusion, p66Shc may be involved in the carcinogenesis of gastric and colorectal cancers and could be a marker for the diagnosis of gastric and colorectal cancers.
C1 [Liu, Ganglei] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
[Xie, Biao] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
[Gong, Lin] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
[Zhou, Jianping] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
[Shu, Guoshun] Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, Hunan, China.
RP Zhou, J (reprint author), Central South University, Second Xiangya Hospital, Department of Geriatric Surgery, 410011 Changsha, China.
EM zhoujiangping88@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 733
EP 739
DI 10.1007/s12253-014-9754-1
PG 7
ER
PT J
AU Marsovszky, L
Resch, DM
Visontai, Zs
Nemeth, J
AF Marsovszky, Laszlo
Resch, D Miklos
Visontai, Zsuzsanna
Nemeth, Janos
TI Confocal Microscopy of Epithelial and Langerhans Cells of the Cornea in Patients Using Travoprost Drops Containing Two Different Preservatives
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Benzalkonium chloride; Confocal microscopy; Langerhans cell; Polyquaternium
ID Benzalkonium chloride; Confocal microscopy; Langerhans cell; Polyquaternium
AB The recently developed confocal cornea microscopy offers the opportunity to examine pathologies of the cornea and to gain insight into the activity of innate immunity. We aimed to investigate the corneal epithelial and Langerhans cell (LC) densities along with dry eye parameters in primary openangle glaucoma (POAG) subjects, treated with either of two commercially available travoprost 0.004 % topical medications containing different preservatives. (1: benzalkonium chloride 0.015 % (TravBAK) and 2: polyquaternium-1 (PQ) 0.001%(TravPQ). Consecutive case series of nineteen POAG patients on TravBAK (mean age: 64.8±13.6 years), nineteen POAG patients on TravPQ (mean age: 66.8±11.3 years) and nineteen age-matched healthy control subjects (63.8±8.2 years). Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), Schirmer test (ST) and tear break up time (TBUT) were assessed, and then corneal epithelial and LC densities were investigated with confocal microscopy. Tear production was significantly reduced in both glaucoma patient groups compared to healthy individuals (p<0.05). TBUT was significantly reduced and epithelial cell densities were significantly greater in patients treated with TravBAK compared to healthy individuals (p<0.05 for all). LC densities were greater in both glaucoma groups compared to control subjects (p<0.05 for all). Travoprost therapy may compromise ocular surface. The limited alertness of the corneal immune system found in patients with TravPQ can be considered as indicators of a less disturbed ocular surface and better controlled corneal homeostasis.
C1 [Marsovszky, Laszlo] Semmelweis University, Department of Ophthalmology, Maria u. 39, 1085 Budapest, Hungary.
[Resch, D Miklos] Semmelweis University, Department of Ophthalmology, Maria u. 39, 1085 Budapest, Hungary.
[Visontai, Zsuzsanna] Semmelweis University, Department of Ophthalmology, Maria u. 39, 1085 Budapest, Hungary.
[Nemeth, Janos] Semmelweis University, Department of Ophthalmology, Maria u. 39, 1085 Budapest, Hungary.
RP Marsovszky, L (reprint author), Semmelweis University, Department of Ophthalmology, 1085 Budapest, Hungary.
EM marsovsz@hotmail.com
CR Martone G, Frezzotti P, Tosi GM, Traversi C, Mittica V, Malandrini A, Pichierri P, Balestrazzi A, Motolese PA, Motolese I, Motolese E, 2009, An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol 147:725–735
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Labbe A, Pauly A, Liang H, Brignole-Baudouin F,Martin C,Warnet JM, Baudouin C, 2006, Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study. J Ocul Pharmacol 22:267–278
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 741
EP 746
DI 10.1007/s12253-014-9755-0
PG 6
ER
PT J
AU Wu, Ch
Yang, Sh
Sun, Z
Han, X
Ye, Y
Liu, Sh
AF Wu, Chunyu
Yang, Shunfang
Sun, Zhenping
Han, Xianghui
Ye, Yiyi
Liu, Sheng
TI Characterization of the Attenuation of Breast Cancer Bone Metastasis in Mice by Zoledronic Acid Using 99mTc bone Scintigraphy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone metastasis; Breast cancer; 99mTc-MDP bone scintigraphy; Zoleronic acid
ID Bone metastasis; Breast cancer; 99mTc-MDP bone scintigraphy; Zoleronic acid
AB Metastatic breast cancer often metastasizes to bone. The purposes of the study were (1) to evaluate the use of 99mTc-MDP bone scintigraphy for detection of metastatic bone lesions, and (2) to determine the efficacy of zoledronic acid in mice with breast cancer bone metastasis. All tumorbearing mice were analyzed with radionuclide bone scintigraphy, X-ray, and histological analysis. The metastatic bone tissue was also harvested and analyzed by western blotting and real-time qPCR. Interestingly, zoledronic acid significantly decreased both the tumor burden and the incidence of bone metastasis in mice. In addition, histomorphometric, stereological, and molecular biology analyses demonstrated that zoledronic acid may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. Finally, the attenuation of breast cancer bone metastasis using zoledronic acid can be accurately characterized by 99mTc bone scintigraphy in mice.
C1 [Wu, Chunyu] Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Department of Breast Surgery, 725 South Wanping Road, 200032 Shanghai, China.
[Yang, Shunfang] Shanghai JiaoTong University, Shanghai Chest Hospital, Department of Nuclear Medicine, 200030 Shanghai, China.
[Sun, Zhenping] Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Department of Breast Surgery, 725 South Wanping Road, 200032 Shanghai, China.
[Han, Xianghui] Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Pharmacology Laboratory of Traditional Chinese Medicine, 200032 Shanghai, China.
[Ye, Yiyi] Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Pharmacology Laboratory of Traditional Chinese Medicine, 200032 Shanghai, China.
[Liu, Sheng] Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Department of Breast Surgery, 725 South Wanping Road, 200032 Shanghai, China.
RP Liu, Sh (reprint author), Shanghai University of Traditional Chinese Medicine, Longhua Hospital, Department of Breast Surgery, 200032 Shanghai, China.
EM sliu_tcm@163.com
CR Chen WQ, Zeng HM, Zheng RS, Zhang SW, He J, 2012, Cancer incidence and mortality in China, 2007. Chin J Cancer Res 24:1–8
Linos E, Spanos D, Rosner BA, Linos K, Hesketh T, Qu JD et al, 2008, Effects of reproductive and demographic changes on breast cancer incidence in China: a modeling analysis. J Natl Cancer Inst 100:1352–1360
Lipton A, Uzzo R, Amato RJ, Ellis GK, Hakimian B, Roodman GD et al, 2009, The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors. J Natl Compr Cancer Netw Suppl 7:S1–S29
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Luo KW, Ko CH, Yue GG, Lee MY, Siu WS, Lee JK et al, 2013, Anti-tumor and anti-osteolysis effects of the metronomic use of zoledronic acid in primary and metastatic breast cancer mouse models. Cancer Lett 339:42–48
Insalaco L, Di Gaudio F, TerrasiM, Amodeo V, Caruso S, Corsini LR et al, 2012, Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells. J Cell Mol Med 16: 2186–2195
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Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M et al, 2002, Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538– 6544
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2014
VL 20
IS 3
BP 747
EP 754
DI 10.1007/s12253-014-9756-z
PG 8
ER
PT J
AU Somoracz,
Korompay, A
Torzsok, P
Patonai, A
Erdelyi-Belle, B
Lotz, G
Schaff, Zs
Kiss, A
AF Somoracz, Aron
Korompay, Anna
Torzsok, Peter
Patonai, Attila
Erdelyi-Belle, Boglarka
Lotz, Gabor
Schaff, Zsuzsa
Kiss, Andras
TI Tricellulin Expression and its Prognostic Significance in Primary Liver Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Tricellulin; Hepatocellular carcinoma; Cholangiocellular carcinoma; Prognosis
ID Tricellulin; Hepatocellular carcinoma; Cholangiocellular carcinoma; Prognosis
AB Numerous data suggest that altered expression of tight junction proteins such as occludin and claudins plays important role in carcinogenesis. However, little is known about tricellulin, a transmembrane tight junction protein concentrated where three epithelial cells meet. We aimed to characterize tricellulin expression in normal and cirrhotic liver in comparison to primary hepatic neoplasms. Tricellulin expression of 20 control livers, 12 cirrhotic livers, 32 hepatocell u l a r carcinomas (HCC), and 20 i n t rahepatic cholangiocarcinomas (iCCC) was investigated by immunohistochemistry and Western blotting. Co-localization of tricellulin with claudin-1, -4, and MRP2 was studied using double immunofluorescence. Scattered tricellulin immunopositivity was restricted to biliary pole of hepatocytes confirmed by co-localization with MRP2. Moreover, spottedlike reaction was observed between bile duct epithelial cells. In 40 % of HCCs marked tricellulin overexpression was measured regardless of tumor grades. In iCCCs, however, tricellulin expression decreased parallel with dedifferentiation. In HCCs high tricellulin expression, in iCCCs low tricellulin expression correlated with poor prognosis. Co-localization with MRP2 might substantiate that tricellulin plays role in blood-biliary barrier. Overexpressed tricellulin in a subset of HCCs correlated with unfavorable prognosis. Similar to ductal pancreatic adenocarcinoma, higher grades of iCCCs were associated with decreased tricellulin expression correlating with poor prognosis.
C1 [Somoracz, Aron] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Korompay, Anna] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Torzsok, Peter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Patonai, Attila] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Erdelyi-Belle, Boglarka] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kiss, A (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM kiss.andras@med.semmelweis-univ.hu
CR Zigler M, Dobroff AS, Bar-Eli M, 2010, Cell adhesion: implication in tumor progression. Minerva Med 101:149–162
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Ikenouchi J, FuruseM, Furuse K et al, 2005, Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171: 939–945
Chiba H, Osanai M, Murata M et al, 2008, Transmembrane proteins of tight junctions. Biochim Biophys Acta 1778:588–600
Riazuddin S, Ahmed ZM, Fanning AS et al, 2006, Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet 79: 1040–1051
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ShinHI, KimBH, ChangHS et al, 2011, Expression of claudin-1 and -7 in clear cell renal cell carcinoma and its clinical significance. Korean J Urol 52:317–322
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 755
EP 764
DI 10.1007/s12253-014-9758-x
PG 10
ER
PT J
AU Michalopoulos, N
Papavramidis, STh
Karayannopoulou, G
Pliakos, I
Papavramidis, TS
Kanellos, I
AF Michalopoulos, Nickos
Papavramidis, S Theodossis
Karayannopoulou, Georgia
Pliakos, Ioannis
Papavramidis, T Spiros
Kanellos, Ioannis
TI Neuroendocrine Tumors of Extrahepatic Biliary Tract
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Neuroendocrine tumor; Carcinoid; Biliary neoplasm; Klatskin tumor; Extrahepatic biliary duct obstruction
ID Neuroendocrine tumor; Carcinoid; Biliary neoplasm; Klatskin tumor; Extrahepatic biliary duct obstruction
AB Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The aim of the present review is to elucidate the characteristics of EBNETs, their treatment and prognosis. An exhaustive systematic review of the literature was performed from 1959 up-to-date. One hundred articles, describing 150 cases were collected. Each article was carefully analyzed and a database was created. The most common symptoms were jaundice (60.3 %) and pruritus (19.2 %). Cholelithiasis co-existed in 15 cases (19.2 %). Hormone- and vasoactive peptide- related symptoms were present in only 7 cases (9 %). The most frequent sites were found to be the common hepatic duct and the proximal common bile duct (19.2 %). Surgical management was considered the main treatment for EBNETs, while excision of extrahepatic biliary tree (62.82 %) with portal vein lymphadenectomy (43.6 %) was the most popular procedure. EBNETs are extremely rare. Their rarity makes their characterization particularly difficult. Up to date the final diagnosis is made after surgery by pathology and immunohistochemistry findings. The present analysis of the existing published cases elucidates many aspects of these tumours, giving complete clinicopathological documentation.
C1 [Michalopoulos, Nickos] Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 85 Karakasi, 54453 Thessaloniki, Greece.
[Papavramidis, S Theodossis] Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 85 Karakasi, 54453 Thessaloniki, Greece.
[Karayannopoulou, Georgia] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology DepartmentThessaloniki, Greece.
[Pliakos, Ioannis] Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 85 Karakasi, 54453 Thessaloniki, Greece.
[Papavramidis, T Spiros] Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 85 Karakasi, 54453 Thessaloniki, Greece.
[Kanellos, Ioannis] Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 85 Karakasi, 54453 Thessaloniki, Greece.
RP Michalopoulos, N (reprint author), Aristotle University of Thessaloniki, AHEPA University Hospital, 3rd Department of Surgery, 54453 Thessaloniki, Greece.
EM nickos.michalopoulos@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 765
EP 775
DI 10.1007/s12253-014-9808-4
PG 11
ER
PT J
AU Eder, K
Kalman, B
AF Eder, Katalin
Kalman, Bernadette
TI Molecular Heterogeneity of Glioblastoma and its Clinical Relevance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Glioblastoma; Inter-tumor heterogeneity; Intra-tumor heterogeneity; Molecular classification; Molecular heterogeneity; Primary brain tumor
ID Glioblastoma; Inter-tumor heterogeneity; Intra-tumor heterogeneity; Molecular classification; Molecular heterogeneity; Primary brain tumor
AB Glioblastoma is the most common intracranial malignancy and constitutes about 50%of all gliomas. Both intertumor and intra-tumor histological heterogeneity had been recognized by the early 1980-ies. Recent works using novel molecular platforms provided molecular definitions of these tumors. Based on comprehensive genomic sequence analyses, The Cancer Genome Atlas Research Network (TCGA) cataloged somatic mutations and recurrent copy number alterations in glioblastoma. Robust transcriptome and epigenome studies also revealed inter-tumor heterogeneity. Integration and cluster analyses of multi-dimensional genomic data lead to a new classification of glioblastoma tumors into subtypes with distinct biological features and clinical correlates. However, multiple observations also revealed tumor area-specific patterns of genomic imbalance. In addition, genetic alterations have been identified that were common to all areas analyzed and other alterations that were area specific. Analyses of intratumor transcriptome variations revealed that in more than half of the examined cases, fragments from the same tumor mass could be classified into at least two different glioblastoma molecular subgroups. Intra-tumor heterogeneity of molecular genetic profiles in glioblastoma may explain the difficulties encountered in the validation of oncologic biomarkers, and contribute to a biased selection of patients for single target therapies, treatment failure or drug resistance. In this paper, we summarize the currently available literature concerning interand intra-tumor molecular heterogeneity of glioblastomas, and call attention to the importance of this topic in relation to the growing efforts in routine molecular diagnostics and personalized therapy.
C1 [Eder, Katalin] Vas County Markusovszky Hospital, Markusovszky Street 5, 9700 Szombathely, Hungary.
[Kalman, Bernadette] Vas County Markusovszky Hospital, Markusovszky Street 5, 9700 Szombathely, Hungary.
RP Eder, K (reprint author), Vas County Markusovszky Hospital, 9700 Szombathely, Hungary.
EM ederkati@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 777
EP 787
DI 10.1007/s12253-014-9833-3
PG 11
ER
PT J
AU Najbauer, J
Kraljik, N
Nemeth, P
AF Najbauer, Joseph
Kraljik, Nikola
Nemeth, Peter
TI Glioma Stem Cells: Markers, Hallmarks and Therapeutic Targeting by Metformin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cancer stem cells; Glioma; Glioma stem cells; Metformin; Therapeutic targeting
ID Cancer stem cells; Glioma; Glioma stem cells; Metformin; Therapeutic targeting
AB Malignant gliomas are among the deadliest primary brain tumors. Despite multimodal therapy and advances in chemotherapy, imaging, surgical and radiation techniques, these tumors remain virtually incurable. Glioma stem cells may be responsible for resistance to traditional therapies and tumor recurrence. Therefore, elimination of glioma stem cells may be crucial for achieving therapeutic efficacy. Metformin, a small molecule drug widely used in the therapy of type 2 diabetes, has shown significant anti-tumor effects in patients with breast cancer and prostate cancer. Recent preclinical data suggest that metformin also has therapeutic effects against glioma. Here we review the markers and hallmarks of glioma stem cells, and the molecular mechanisms involved in therapeutic targeting of glioma stem cells by metformin.
C1 [Najbauer, Joseph] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
[Kraljik, Nikola] Institute of Public Health for the Osijek-Baranja County, F. Krezme 1, 31000 Osijek, Croatia.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
RP Najbauer, J (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7624 Pecs, Hungary.
EM jnajbauer@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 789
EP 797
DI 10.1007/s12253-014-9837-z
PG 9
ER
PT J
AU Chen, W
Jiang, X
Luo, Z
AF Chen, Wei
Jiang, Xiaofei
Luo, Zhuang
TI WWP2: A Multifunctional Ubiquitin Ligase Gene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE WWP2 (AIP2); Ubiquitylation; Cancer
ID WWP2 (AIP2); Ubiquitylation; Cancer
AB The ubiquitin-proteasome system plays an important role in various celluar processes. WWP2, a recently identified ubiquitin E3 ligase, has been proved a multifunctional gene by degradation a series of targets via ubiquitindependent proteasome system, including PETN, Smads, Oct4, EGR2, TIRF and so. Hereafter, we reviewed the recent research process about the function of WWP2.
C1 [Chen, Wei] Sichuan North Medical College, Department of Pathophysiology, 637100 Nanchong, China.
[Jiang, Xiaofei] The Seventh People’s Hospital of Chengdu, Department of General Surgery, 610041 Chengdu, China.
[Luo, Zhuang] Kunming Medical University, First Affiliated Hospital, Department of Respiratory Diseases, 650032 Kunming, China.
RP Luo, Z (reprint author), Kunming Medical University, First Affiliated Hospital, Department of Respiratory Diseases, 650032 Kunming, China.
EM skyny4511@126.com
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Lu D, Davis MP, Abreu-Goodger C, Wang W, Campos LS, Siede J, Vigorito E, SkarnesWC, Dunham I, Enright AJ et al, 2012, MiR-25 regulatesWwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs. PLoS ONE 7(8):e40938
Chen A, Gao B, Zhang J, McEwen T, Ye SQ, Zhang D, Fang D, 2009, The HECT-type E3 ubiquitin ligase AIP2 inhibits activationinduced T-cell death by catalyzing EGR2 ubiquitination. Mol Cell Biol 29(19):5348–5356
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Foot NJ, Dalton HE, Shearwin-Whyatt LM,Dorstyn L, Tan SS, Yang B, Kumar S, 2008, Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2. Blood 112(10):4268–4275
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 799
EP 803
DI 10.1007/s12253-014-9838-y
PG 5
ER
PT J
AU Hu, X
Xin, Y
Xiao, Y
Zhao, J
AF Hu, Xiaobin
Xin, Yan
Xiao, Yuping
Zhao, Jing
TI Overexpression of YAP1 is Correlated with Progression, Metastasis and Poor Prognosis in Patients with Gastric Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE YAP1; Gastriccarcinoma; Metastasis; Prognosis
ID YAP1; Gastriccarcinoma; Metastasis; Prognosis
AB YAP1 is overexpressed in numerous cancers, but its molecular mechanism in the carcinogenesis and clinic significance in tumor diagnosis and prognosis remains to be determined. We attempted to analyze the clinicopathologic significance of YAP1 expression and the correlation of the YAP1 levels with the progression, metastasis and prognosis of patients with gastric carcinoma. By immunohistochemistry, we determined YAP1 expression in 214 of primary gastric carcinoma (GC), 167 of matched normal gastric mucosa, 40 of chronic atrophic gastritis, 11 of dysplasia and 73 of intestinal metaplasia. The positive rate of YAP1 in gastric carcinoma was significantly higher than that in normal gastric mucosa, chronic atrophic gastritis and intestinal metaplasia. In the gastric cancers with lymph node metastasis, the positive rate of YAP1 was much higher than that in the group without lymph nodemetastasis. Moreover, gastric cancer patients with YAP1 overexpression demonstrated poorer prognosis than those with YAP1 negative staining. Finally, multivariate analysis of 191 patients with gastric carcinoma indicated that YAP1 overexpression, the invasion depth and lymph node metastasis were high hazard factors for gastric carcinoma. Our results demonstrated that YAP1 overexpression is correlated to the progression, lymph node metastasis and poor prognosis of gastric carcinoma, suggesting that overexpression of YAP1 might be an adjuvant factor for predicting lymph node metastasis, and a useful biomarker for the diagnosis and prediction of prognosis in patients with gastric cancers.
C1 [Hu, Xiaobin] No. 1 Hospital of China Medical University, Cancer Institute and Department of Pediatrics, 155 North Nanjing Street, Heping District, 110001 Shenyang, Liaoning Province, China.
[Xin, Yan] China Medical University, The First Affiliated Hospital, Department of General Surgery, 155 North Nanjing Street, Heping District, 110001 Shenyang, Liaoning Province, China.
[Xiao, Yuping] China Medical University, The First Affiliated Hospital, Department of General Surgery, 155 North Nanjing Street, Heping District, 110001 Shenyang, Liaoning Province, China.
[Zhao, Jing] China Medical University, The First Affiliated Hospital, Department of General Surgery, 155 North Nanjing Street, Heping District, 110001 Shenyang, Liaoning Province, China.
RP Xin, Y (reprint author), China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
EM yxin@mail.cmu.edu.cn
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OverholtzerM, Zhang J, Smolen GA,Muir B, LiW, Sgroi DC, Deng CX, Brugge JS, Haber DA, 2006, Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci U S A 103:12405–12410
Tufail R, Jorda M, Zhao W, Reis I, Nawaz Z, 2011, Loss of Yesassociated protein, YAP, expression is associated with estrogen and progesterone receptors negativity in invasive breast carcinomas. Breast Cancer Res Treat 131:743–750
Steinhardt AA, Gayyed MF, Klein AP, Dong J, Maitra A, Pan D, Montgomery EA, Anders RA, 2008, Expression of Yes-associated protein in common solid tumors. Hum Pathol 39:1582–1589
Zhang J, Ji JY, Yu M, Overholtzer M, Smolen GA, Wang R, Brugge JS, Dyson NJ, Haber DA, 2009, YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat Cell Biol 11:1444–1450
Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT, Luk JM, 2009, Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer 115:4576–4585
Lam-Himlin DM, Daniels JA, Gayyed MF, Dong J, Maitra A, Pan D, Montgomery EA, Anders RA, 2006, The hippo pathway in human upper gastrointestinal dysplasia and carcinoma: a novel oncogenic pathway. Int J Gastrointest Cancer 37:103– 109
KangW, Tong JH, Chan AW, Lee TL, Lung RW, Leung PP, So KK, Wu K, Fan D, Yu J, Sung JJ, To KF, 2011, Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Clin Cancer Res 17:2130– 2139
Da CL, Xin Y, Zhao J, Luo XD, 2009, Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions. World J Gastroenterol 15:4055–4061
Song M, Cheong JH, Kim H, Noh SH, Kim H, 2012, Nuclear expression of Yes-associated protein 1 correlates with poor prognosis in intestinal type gastric cancer. Anticancer Res 32:3827–3834
Zhang J, Xu ZP, Yang YC, Zhu JS, Zhou Z, Chen WX, 2012, Expression of Yes-associated protein in gastric adenocarcinoma and inhibitory effects of its knockdown on gastric cancer cell proliferation and metastasis. Int J Immunopathol Pharmacol 25:583–590
Zhang J, Yang YC, Zhu JS, Zhou Z, Chen WX, 2012, Clinicopathologic characteristics of YES-associated protein 1 overexpression and its relationship to tumor biomarkers in gastric cancer. Int J Immunopathol Pharmacol 25:977–987
Zhou GX, Li XY, Zhang Q, Zhao K, Zhang CP, Xue CH, Yang K, Tian ZB, 2013, Effects of the hippo signaling pathway in human gastric cancer. Asian Pac J Cancer Prev 14:5199–5205
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 805
EP 811
DI 10.1007/s12253-014-9757-y
PG 7
ER
PT J
AU Becsagh, P
Szakacs, O
AF Becsagh, Peter
Szakacs, Orsolya
TI Setting Up a Probe Based, Closed Tube Real-Time PCR Assay for Focused Detection of Variable Sequence Alterations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE qPCR; Taqman probe; Simple probe; c-Kit; Mutations; DNA
ID qPCR; Taqman probe; Simple probe; c-Kit; Mutations; DNA
AB During diagnostic workflow when detecting sequence alterations, sometimes it is important to design an algorithm that includes screening and direct tests in combination. Normally the use of direct test, which is mainly sequencing, is limited. There is an increased need for effective screening tests, with "closed tube" during the whole process and therefore decreasing the risk of PCR product contamination. The aim of this study was to design such a closed tube, detection probe based screening assay to detect different kind of sequence alterations in the exon 11 of the human c-kit gene region. Inside this region there are variable possible deletions and single nucleotide changes. During assay setup, more probe chemistry formats were screened and tested. After some optimization steps the taqman probe format was selected.
C1 [Becsagh, Peter] Roche Hungary LtdBudaors, Hungary.
[Szakacs, Orsolya] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
RP Becsagh, P (reprint author), Roche Hungary Ltd, Budaors, Hungary.
EM peter.becsagh@roche.com
CR Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, Besmer P, 2003, Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 9(9):3329–3337
Kondiah K, Swanepoel R, Paweska JT, Burt FJ, 2010, A simpleprobe real-time PCR assay for genotyping reassorted and nonreassorted isolates of Crimean-Congo hemorrhagic fever virus in southern Africa. J Virol Methods 169(1):34–38
Grannemann S, Landt O, Breuer S, Blomeke B, 2005, LightTyper assay with locked-nucleic-acid-modified oligomers for genotyping of the toll-like receptor 4 polymorphisms A896G and C1196T. Clin Chem 51(8):1523–1525
Frances F, Corella D, Sorli JV, Guillen M, Gonzalez JI, Portoles O, 2005, Validating a rapid method for detecting common polymorphisms in the APOA5 gene by melting curve analysis using LightTyper. Clin Chem 51:1279–1282
Frances F, Portoles O, Sorli JV, Guillen M, Gonzalez JI, Corella D, 2008, Single tube optimisation of APOE genotyping based on melting curve analysis. Clin Biochem 41(10–11):923–926
McGuigan FE, Ralston SH, 2002, Single nucleotide polymorphism detection: allelic discrimination using TaqMan. Psychiatr Genet 12(3):133–136
Hui L, DelMonte T, Ranade K, 2008, Genotyping using the TaqMan assay. Curr Protoc Hum Genet., DOI 10.1002/0471142905.hg0210s56
Zhou L, Myers AN, Vandersteen JG, Wang L, Wittwer CT, 2004, Closed-tube genotyping with unlabeled oligonucleotide probes and a saturating DNA dye. Clin Chem 50(8):1328–1335
Roche Applied Science, 2004, LightCycler Manual, Technical Note No. LC 18/2004: Assay formats for use in real-time PCR. https:// www.roche-applied-science.com/sis/rtpcr/lightcycler/ lightcycler—docs/technical—notes/lc—18.pdf
Mackay J, Landt O, 2007, Real-time PCR fluorescent chemistries. Methods Mol Biol 353:237–261
Korbie DJ, Mattick JS, 2008, Touchdown PCR for increased specificity and sensitivity in PCR amplification. Nat Protoc 3(9):1452–1456
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 813
EP 818
DI 10.1007/s12253-014-9759-9
PG 6
ER
PT J
AU Alshenawy, AH
AF Alshenawy, AlSaeid Hanan
TI Utility of Immunohistochemical Markers in Diagnosis of Follicular Cell Derived Thyroid Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid carcinoma; Immunohistochemistry; CD56; HBME-1; Gatectin-3; CK19
ID Thyroid carcinoma; Immunohistochemistry; CD56; HBME-1; Gatectin-3; CK19
AB Differentiating the follicular derived lesions can be challenging. Although immunohistochemistry is generally accepted as a useful ancillary technique in the diagnosis, controversy exists regarding the best marker or combination of markers to distinguish each lesion from its mimics. In this study, we aimed at evaluating multiple markers to compare their sensitivity and usefulness, and to find out if a combination of the evaluated markers can be of additional value in discriminating thyroid lesions. The study included two groups of follicular derived thyroid lesions; benign group (Grave’s disease, nodular goiter, Hashimoto’s and adenoma) and malignant group (papillary, follicular carcinoma, well differentiated tumors of unknown malignant potential and follicular tumour of unknown malignant potential). Immunohistochemical evaluation of CD56, HBME-1, Gaectin-3 and CK19 were done. The sensitivity, specificity for each marker and their combination were calculated. Each marker was sensitive and specific for certain lesion but the sensitivity and specificity was increased when use combination of markers. Although no single marker is completely sensitive and specific for follicular thyroid lesions, the combination of CD56, HBME-1, Gaectin-3 and CK19 attains high sensitivity and specificity in diagnosis.
C1 [Alshenawy, AlSaeid Hanan] Tanta University, Faculty of Medicine, Department of Pathology, 25 Hamdy Gado streetTanta, Egypt.
RP Alshenawy, AH (reprint author), Tanta University, Faculty of Medicine, Department of Pathology, Tanta, Egypt.
EM hanan_alshenawy@yahoo.com
CR Ying YL, Hans M, Job K et al, 2008, Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-g, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma. Eur J Endocrinol 158:375–384
Guido F, Esther DR, Marco R et al, 2011, Follicular thyroid neoplasms can be classified as low- and high-risk according to HBME-1 andGalectin-3 expression on liquid-based fine-needle cytology. Eur J Endocrinol 165:447–453
Yoon LC, Mi KK, Jin-Won S et al, 2005, Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci 20(5):853–859
Yasuhiro I, Hiroshi Y, Chisato T et al, 2005, HBME-1 expression in follicular tumor of the thyroid: an investigation of whether it can be used as amarker to diagnose follicular carcinoma. AnticancerRes 25:179–182
Arturs O, Zenons N, Ilze S et al, 2012, Immunohistochemical expression of HBME-1, E-cadherin, and CD56 in the differential diagnosis of thyroid nodules. Medicina, Kaunas, 48(10):507–514
Mauro P, Jaime R, Roberta DP et al, 2005, Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 18:541–546
Dina ED, Ahmed N, Salem A, 2008, Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid. Diagn Pathol 3–5
Jeffrey L, Bhuvanesh S, Giovanni T et al, 2006, Follicular variant of papillary thyroid carcinoma. A clinicopathologic study of a problematic entity. Cancer 107(6):1255–1264
Debdas B, Ram ND, Uttara C et al, 2012, Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma. Indian J Med Paediatr Oncol 33(2):107–111
RashaMA, Lobna SS, 2012, Potential diagnostic utility of CD56 and claudin-1 in papillary thyroid carcinoma and solitary follicular thyroid nodules. J Egypt Natl Cancer Inst 24:175–184
Husain AS, Jining F, Farah T et al, 2009, Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cytojournal 6:18
Young JP, Soo HK, Dong CK et al, 2007, Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27kip1 in the differential diagnosis of thyroid nodules. J Korean Med Sci 22(4):621–628
Sandrine R, Brahim E, Sergio F et al, 2002, Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications.Mod Pathol 15(12):1294–1301
Prasad ML, Pellegata NS, Huang Y et al, 2005, Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57
de Matos PS, Ferreira AP, de Oliveira FF et al, 2005, Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 47:391–401
Ozolins A, Narbuts Z, Strumfa I et al, 2010, Diagnostic utility of immunohistochemical panel in various thyroid pathologies. Langenbecks Arch Surg 395(7):885–891
DeLellis RA, 2006, Pathology and genetics of thyroid carcinoma. J Surg Oncol 94(8):662–669
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Park WY, Jeong SM, Lee JH et al, 2009, Diagnostic value of decreased expression of CD56 protein in papillary carcinoma of the thyroid gland. Basic Appl Pathol 2:63–68
Nasr MR, Mukhopadhyay S, Zhang S et al, 2006, Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME 1 combined with CK-19 immunostaining. Mod Pathol 19:1631–1637
Husain AS, Bo J, John B et al, 2010, Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol 5:9
Qingbin S, Deguang W, Yi L et al, 2011, Diagnostic significance of CK19, TG, Ki67 and galectin-3 expression for papillary thyroid carcinoma in the northeastern region of China. Diagn Pathol 6:126– 131
Shin MK, Kim JW, Ju Y, 2011, CD56 and high molecular weight keratin as dignostic markers of papillary thyroid carcinoma. Korean J Pathol 45:477–484
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MiettinenM, Karkkainen P, 1996, Differential reactivity ofHBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Virchows Arch 429:213–219
Cheung CC, Ezzat S, Freeman JL e t a l, 2001, Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 14:338–342
Gasbarri A, Martegani MP, Del Prete F et al, 1999, Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 17:3494–3499
Saggiorato E, De Pompa R, Volante M et al, 2005, Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocrinol Relat Cancer 12:305–317
Orlandi F, Saggiorato E, Pivano G et al, 1998, Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 58: 3015–3020
Kovacs RB, Foldes J, Winkler G et al, 2003, The investigation of galectin-3 in diseases of the thyroid gland. Eur J Endocrinol 149(5): 449–453
Bartolazzi A, Gasbarri A, Papotti M et al, 2001, Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650
Collet JF, Fajac A, 2006, Galectin-3 immunodetection in thyroid fine-needle aspirates: technical procedure and results. Ann Pathol 26:347–351
KimMJ, Kim HJ, Hong SJ et al, 2006, Diagnostic utility of galectin- 3 in aspirates of thyroid follicular lesions. Acta Cytol 50:28–34
Sahoo S, Hoda SA, Rosai J et al, 2001, Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma. Am J Clin Pathol 116:696–702
Guyetant S,Michalak S,Valo I et al, 2003, Diagnosis of the follicular variant of papillary thyroid carcinoma significance of immunohistochemistry. Ann Pathol 23:11–20
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 819
EP 828
DI 10.1007/s12253-014-9760-3
PG 10
ER
PT J
AU Tang, Y
Jiang, L
Tang, W
AF Tang, Yongyong
Jiang, Li
Tang, Wei
TI Decreased Expression of NPRL2 in Renal Cancer Cells is Associated with Unfavourable Pathological, Proliferation and Apoptotic Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NPRL2; Renal cancer carcinoma; Transfection; Proliferation; Apoptosis
ID NPRL2; Renal cancer carcinoma; Transfection; Proliferation; Apoptosis
AB The tumor suppressor gene nitrogen permease regulator-like 2(NPRL2) NPRL2 expressed obviously in many normal human tissues, but reduced in expression in many human tumors significantly. In this study, we detected the expression of NPRL2 in 78 clear cell renal cell carcinoma (ccRCC) by immunohistochemistry and correlated it with clinicopathological parameters. Meanwhile, the function of NPRL2 in human ccRCC was further explored after transfected recombinant expressing plasmids pEGFP-N1- NPRL2 into human renal cancer 786-0 cells. NPRL2 protein showed high expression in 67 of 78 cases of adjacent normal tissues (85.9 %), which was significantly higher than that in ccRCC tissues (23/78, 29.5 %). Clinic pathological analysis showed that NPRL2 expression was significantly correlated with histological grade (P=0.044), TNM stage (P=0.025) and lymph node metastasis (P=0.028). MTT assay demonstrated that NPRL2 could obviously inhibit renal cancer cell proliferation. Flow cytometric analysis revealed that NPRL2 could induce renal cancer cells apoptosis and arrest the cell cycle in G0/G1 phase. In conclusion, NPRL2 is closely correlated to unfavourable pathological, proliferation and apoptotic features in ccRCC.
C1 [Tang, Yongyong] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, No.1 Medical College Road, Yuzhong District, 400016 Chongqing, China.
[Jiang, Li] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, No.1 Medical College Road, Yuzhong District, 400016 Chongqing, China.
[Tang, Wei] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, No.1 Medical College Road, Yuzhong District, 400016 Chongqing, China.
RP Tang, W (reprint author), Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
EM tangwei2060@163.com
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics, 2013. CA Cancer J Clin 63:11–30
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Jemal A, Siegel R, Ward E et al, 2008, Cancer statistics, 2008. CA Cancer J Clin 58:71–96
Arsanious A, Bjarnason GA, Yousef GM, 2009, From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma. Mol Cancer 8(1):20
Jiang Z, Chu PG, Woda BA, Liu Q, Balaji KC, Rock KL, Wu CL, 2008, Combination of quantitative IMP3 and tumor stage: a new system to predict metastasis for patients with localized renal cell carcinomas. Clin Cancer Res 14:5579–5584
Lee JW, Bae SH, Jeong JW et al, 2004, Hypoxia-inducible factor, HIF-1)alpha: its protein stability and biological functions. Exp Mol Med 36(1):1–12
Hirota, Yan L, Tsunoda Tet al, 2006, Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma. Int J Oncol 29(4):799– 827
Lerman MI, Minna JD, 2000, The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 60(21):6116–6133
Li J, Wang F, Haraldson et al, 2004, Functional characterization of the candidate tumor suppressor gene NPRL2/G21 located in 3p21.3C. Cancer Res 64(18):6438–6443
Sasatomi E, Finkelstein SD, Woods JD et al, 2002, Comparison of accumulated allele loss between primary tumor and lymph node metastasis in stage II non-small cell lung carcinoma: implications for the timing of lymph nodemetastasis and prognostic value. Cancer Res 62(9):2681–2689
Senchenko VN, Anedchenko EA, Kondratieva TT et al, 2010, Simultaneous down-regulation of tumor suppressor genes RBSP3/ CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC Cancer 10:75
Otani S, Takeda S, Yamada S, Sakakima Y et al, 2009, The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor. J Surg Oncol 100(5):358–363
Zabarovsky ER, Lerman MI, Minna JD, 2002, Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene 21(45):6915–6935
Yi Lo PH, Chung Leung AC, Xiong W et al, 2006, Expression of candidate chromosome 3p21.3 tumor suppressor genes and downregulation of BLU in some esophageal squamous cell carcinomas. Cancer Lett 234(2):184–192
Chow LS, Lo KW, Kwong J et al, 2004, RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma. Int J Cancer 109(6):839–847
Li J, Wang F, Protopopov A et al, 2004, Inactivation of RASSF1C during in vivo tumor growth identifies it as a tumor suppressor gene. Oncogene 23(35):5941–5949
Wang F, Grigorieva EV, Li J et al, 2008, HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro. PLoS One 3(8):e3031
Senchenko et al, 2010, Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC Cancer 10:75
Jayachandran G, Ueda K, Wang B, Roth JA, Ji L, 2010, NPRL2 sensitizes human non-small cell lung, NSCLC, cells to cisplatin treatment by regulating components in the DNA repair pathway. PLoS One 5(8):e11994
Otani S, Takeda S, Yamada S et al, 2009, The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor. J Surg Oncol 100:358–363
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Xue et al, 2012, Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma. J Transl Med 10:200
Otani S, Takeda S, Yamada S et al, 2009, The tumor supperessor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor. J Surg Oncol 100(5):358–363
Gao Y, Wang J, Fan G, 2012–2013, NPRL2 is an independent prognostic factor of osteosarcoma. Cancer Biomark 12(1):31–36
Yogurtcu B,Hatemi I,Aydin I et al, 2012)NPRL2 gene expression in the progression of colon tumors. Genet Mol Res 11(4):4810–4816
Ji L, Nishizaki M, Gao B et al, 2002, Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo. Cancer Res 62(9):2715–2720
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Economidou F, Tzortzaki EG, Schiza S et al, 2007, Microsatellite DNA analysis does not distinguish malignant from benign pleural effusions. Oncol Rep 18(6):1507–1512
Castagnaro A, Marangio E, Verduri A et al, 2007, Microsatellite analysis of induced sputum DNA in patients with lung cancer in heavy smokers and in healthy subjects. Exp Lung Res 33(6): 289–301
Kurata A, Katayama R, Watanabe T et al, 2008, TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling. Cancer Sci 99(9):1827–1834
Kim JH, Kim H, Lee KY et al, 2006, Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. HumMol Genet 15(7):1181–1186
Wang YX, Zhu SC, Feng W, Li J, Su JW, Li R, 2006, Effect on retardation of G2/M phase in esophageal carcinoma cells transfected with CHK1 and CHK2 shRNA after irradiation. Zhonghua Zhong Liu Za Zhi 28(8):572–577
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 829
EP 837
DI 10.1007/s12253-014-9761-2
PG 9
ER
PT J
AU Raza, Y
Khan, A
Farooqui, A
Mubarak, M
Facista, A
Akhtar, ShS
Khan, S
Kazi, IJ
Bernstein, C
Kazmi, USh
AF Raza, Yasir
Khan, Adnan
Farooqui, Amber
Mubarak, Muhammad
Facista, Alex
Akhtar, Shakeel Syed
Khan, Saeed
Kazi, Iqbal Javed
Bernstein, Carol
Kazmi, Urooj Shahana
TI Oxidative DNA Damage as a Potential Early Biomarker of Helicobacter pylori Associated Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Helicobacter pylori; Gastritis; 8-hydroxy-2′-deoxyguanosine; Gastric cancer; Immunohistochemistry
ID Helicobacter pylori; Gastritis; 8-hydroxy-2′-deoxyguanosine; Gastric cancer; Immunohistochemistry
AB Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid- Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori. The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) (p≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori-associated gastric carcinogenesis.
C1 [Raza, Yasir] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
[Khan, Adnan] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
[Farooqui, Amber] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
[Mubarak, Muhammad] Sindh Institute of Urology and Transplantation, Department of HistopathologyKarachi, Pakistan.
[Facista, Alex] University of Arizona, College of Medicine, Department of Cellular and Molecular MedicinePhoenix, AZ, USA.
[Akhtar, Shakeel Syed] Civil Hospital Karachi, Department of Surgery and MedicineKarachi, Pakistan.
[Khan, Saeed] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
[Kazi, Iqbal Javed] Sindh Institute of Urology and Transplantation, Department of HistopathologyKarachi, Pakistan.
[Bernstein, Carol] University of Arizona, College of Medicine, Department of Cellular and Molecular MedicinePhoenix, AZ, USA.
[Kazmi, Urooj Shahana] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
RP Mubarak, M (reprint author), Sindh Institute of Urology and Transplantation, Department of Histopathology, Karachi, Pakistan.
EM drmubaraksiut@yahoo.com
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Inokuma T, Haraguchi M, Fujita F, Tajima Y, Kanematsu T, 2009, Oxidative stress and tumor progression in colorectal cancer. Hepatogastroenterology 56:343–347
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 839
EP 846
DI 10.1007/s12253-014-9762-1
PG 8
ER
PT J
AU Xing, J
Cao, G
Fu, Ch
AF Xing, Junjie
Cao, Guangwen
Fu, Chuangang
TI HMGA1 Interacts with β-Catenin to Positively Regulate Wnt/β-Catenin Signaling in Colorectal Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; HMGA1; β-catenin; Wnt signaling pathway
ID Colorectal cancer; HMGA1; β-catenin; Wnt signaling pathway
AB The high mobility group A1 (HMGA1) protein plays an important role in numerous biological processes, such as embryogenesis, cell proliferation, differentiation, apoptosis and carcinogenesis.Wnt/β-catenin signaling pathway plays a key role in development and cancer. Although previous reports have shown HMGA1 protein level can be induced by Wnt/β-catenin signaling pathway, however, the specific mechanism of HMGA1 on regulating Wnt/β-catenin signaling remains unclear. Here, we reported that HMGA1 interacted with β-catenin by using coimmunoprecipitation approach with exogenous and endogenous protein samples. HMGA1 positively regulated Wnt/β-catenin signaling, as determined by that HMGA1 increased the TOP-FLASH activity in a dose-dependent manner and β-catenin downstream target gene expression. Moreover, HMGA1 induced proliferation of colorectal cancer cells. Mechanistically, HMGA1 increased the β-catenin–TCF4 complex formation. Importantly, there was a correlation between HMGA1 and β-catenin expression in human colorectal cancer tissues. In summary, HMGA1 positively regulates Wnt/β-catenin signaling through interacting with β-catenin, which leads to increase the β-catenin–TCF4 complex formation. This suggests that targeting HMGA1 may be a useful therapeutic option in clinical application.
C1 [Xing, Junjie] Second Military Medical University, Changhai Hospital, Department of Colorectal SurgeryShanghai, China.
[Cao, Guangwen] Second Military Medical University, Department of EpidemiologyShanghai, China.
[Fu, Chuangang] Second Military Medical University, Changhai Hospital, Department of Colorectal SurgeryShanghai, China.
RP Fu, Ch (reprint author), Second Military Medical University, Changhai Hospital, Department of Colorectal Surgery, Shanghai, China.
EM fugang416@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 847
EP 851
DI 10.1007/s12253-014-9763-0
PG 5
ER
PT J
AU Huang, P
Cao, K
Zhao, H
AF Huang, Ping
Cao, Kejian
Zhao, Heng
TI Screening of Critical Genes in Lung Adenocarcinoma via Network Analysis of Gene Expression Profile
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; Gene expression profile; Differentially expressed gene; Gene expression core signature; Functional enrichment analysis; Network clustering
ID Lung adenocarcinoma; Gene expression profile; Differentially expressed gene; Gene expression core signature; Functional enrichment analysis; Network clustering
AB Biomarker discovery is of great importance in diagnosis and treatment of diseases. In present study, a number of differentially expressed genes (DEGs) were identified for lung adenocarcinoma via comparative analysis of gene expression data. A gene expression core signature was generated for four types of lung adenocarcinoma (EGFR-mutated, KRAS-mutated, ALK-mutated and triple-negative adenocarcinoma). Functional enrichment analysis with DAVID tools revealed that up-regulated genes were mainly associated with cell cycle while down-regulated genes were mainly involved in vasculature development and cell adhesion. Then it was used to retrieve relevant small molecule drugs with Connectivity map and trichostatin A was predicted to be the top candidate drug for treatment of lung cancer. Network clustering was performed with MCL in cytoscape to identify sub-networks and several hub genes were obtained: CDC25C, ICT1, TK1 and EZH2. These genes play important roles in the progression of lung cancer and some have been suggested as potential biomarkers. Therefore, our findings are beneficial in deepening the understandings about the pathogenesis and providing directions for future researches.
C1 [Huang, Ping] Shanghai Jiao Tong University, Shanghai Chest Hospital, Department of Thoracic Surgery, NO.241 Huaihaixi Road, 200030 Shanghai, China.
[Cao, Kejian] Shanghai Jiao Tong University, Shanghai Chest Hospital, Department of Thoracic Surgery, NO.241 Huaihaixi Road, 200030 Shanghai, China.
[Zhao, Heng] Shanghai Jiao Tong University, Shanghai Chest Hospital, Department of Thoracic Surgery, NO.241 Huaihaixi Road, 200030 Shanghai, China.
RP Zhao, H (reprint author), Shanghai Jiao Tong University, Shanghai Chest Hospital, Department of Thoracic Surgery, 200030 Shanghai, China.
EM H_zhang28@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 853
EP 858
DI 10.1007/s12253-014-9764-z
PG 6
ER
PT J
AU Shabayek, IM
Sayed, MO
Attaia, AH
Awida, AH
Abozeed, H
AF Shabayek, I Marwa
Sayed, M Ola
Attaia, A Hanan
Awida, A Heba
Abozeed, Hamdy
TI Diagnostic Evaluation of Urinary Angiogenin (ANG) and Clusterin (CLU) as Biomarker for Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder; Cancer; Cytology; Angiogenin; Clusterin; Sensitivity
ID Bladder; Cancer; Cytology; Angiogenin; Clusterin; Sensitivity
AB Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n=50), benign (n=20) and healthy (n=20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.
C1 [Shabayek, I Marwa] Future University, Faculty of Pharmaceutical Sciences and Pharmaceutical Technologies, Department of BiochemistryCairo, Egypt.
[Sayed, M Ola] Azhar University, Faculty of Pharmacy, Department of BiochemistryCairo, Egypt.
[Attaia, A Hanan] Azhar University, Faculty of Pharmacy, Department of BiochemistryCairo, Egypt.
[Awida, A Heba] Future University, Faculty of Pharmaceutical Sciences and Pharmaceutical Technologies, Department of BiochemistryCairo, Egypt.
[Abozeed, Hamdy] Azhar University, Faculty of Medicine, Urology DepartmentCairo, Egypt.
RP Shabayek, IM (reprint author), Future University, Faculty of Pharmaceutical Sciences and Pharmaceutical Technologies, Department of Biochemistry, Cairo, Egypt.
EM biochemistry.fue@gmail.com
CR American Cancer Society, 2013, Cancer facts and figures 2013. American Cancer Society, Atlanta
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 859
EP 866
DI 10.1007/s12253-014-9765-y
PG 8
ER
PT J
AU Sipos, F
Muzes, Gy
Furi, I
Spisak, S
Wichmann, B
Germann, MT
Constantinovits, M
Krenacs, T
Tulassay, Zs
Molnar, B
AF Sipos, Ferenc
Muzes, Gyorgyi
Furi, Istvan
Spisak, Sandor
Wichmann, Barnabas
Germann, M Tiana
Constantinovits, Miklos
Krenacs, Tibor
Tulassay, Zsolt
Molnar, Bela
TI Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Free-circulating DNA; DSS-colitis; Toll-like receptor 9; Proinflammatory cytokines; Tissue regeneration
ID Free-circulating DNA; DSS-colitis; Toll-like receptor 9; Proinflammatory cytokines; Tissue regeneration
AB In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitisderived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.
C1 [Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Muzes, Gyorgyi] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Furi, Istvan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Spisak, Sandor] Harvard Medical School, Dana-Farber Cancer Institute, Department of Medical OncologyBoston, MA, USA.
[Wichmann, Barnabas] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Germann, M Tiana] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Constantinovits, Miklos] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Street 46, 1088 Budapest, Hungary.
RP Sipos, F (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM dr.siposf@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 867
EP 877
DI 10.1007/s12253-014-9766-x
PG 11
ER
PT J
AU Aoki, J
Tsubokura, M
Kakihana, K
Oshikawa, G
Kobayashi, T
Doki, N
Sakamaki, H
Ohashi, K
AF Aoki, Jun
Tsubokura, Masaharu
Kakihana, Kazuhiko
Oshikawa, Gaku
Kobayashi, Takeshi
Doki, Noriko
Sakamaki, Hisashi
Ohashi, Kazuteru
TI The Predictive Value for Pulmonary Infection by Area Over the Neutrophil Curve (D-index) in Patients Who Underwent Reduced Intensity Hematopoietic Stem Cell Transplantation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE D-index; cD-index; D21-index; Pulmonary infection; Reduced intensity conditioning regimen
ID D-index; cD-index; D21-index; Pulmonary infection; Reduced intensity conditioning regimen
AB We evaluated the predictive value of the D-index for pulmonary infection in the early phase of reduced intensity stem cell transplantation (RIST). Out of 68 patients, ten patients developed a pulmonary infection within 100 days after RIST. Both the D-index and the cD-index were higher in the patients with pulmonary infection than in the control group (P=0.009, P=0.042, respectively). The best sensitivity and specificity, calculated with receiver operating characteristic curves, showed that the D-index was superior to the duration of neutropenia in predicting pulmonary infection. We also evaluated the utility of a cumulative D-index until 21 days after RIST (D21-index). The D21-index was higher in the patients with pulmonary infection (P=0.047). The cutoff value of the D21-index was lower than that of the D-index (8650 vs. 11000) with comparable sensitivity and specificity. Our results demonstrate that the D21-index, as well as the D-index, are useful tools for the prediction of pulmonary infection in RIST.
C1 [Aoki, Jun] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Tsubokura, Masaharu] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Oshikawa, Gaku] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashi, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Doki, Noriko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Kakihana, K (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM kakihana@cick.jp
CR Engels EA, Ellis CA, Supran SE, Schmid CH, Barza M, Schenkein DP, Koc Y, Miller KB, Wong JB, 1999, Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk. Clin Infect Dis 28(2):256–266., DOI 10.1086/515103
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Kimura S, Oshima K, Sato K, Sato M, Terasako K, Nakasone H, Kikuchi M, Okuda S, Kako S, Yamazaki R, Tanaka Y, Tanihara A, Nishida J, Kanda Y, 2010, Retrospective evaluation of the area over the neutrophil curve index to predict early infection in hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant 16(10):1355–1361., DOI 10.1016/j.bbmt.2010.04.012
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 879
EP 883
DI 10.1007/s12253-014-9768-8
PG 5
ER
PT J
AU Li, F
Wang, W
Li, L
Chang, Y
Su, D
Guo, G
He, X
Li, M
AF Li, Fenqiang
Wang, Wenhui
Li, Li
Chang, Yaowen
Su, Dongjun
Guo, Gang
He, Xuewen
Li, Mingxiang
TI An Effective Therapy to Painful Bone Metastases: Cryoablation Combined with Zoledronic Acid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pain; Bone metastases; Cryoablation; Zoledronic acid; Combined therapy; Efficacy
ID Pain; Bone metastases; Cryoablation; Zoledronic acid; Combined therapy; Efficacy
AB Approximately half or more of patients diagnosed with late malignant tumors may suffer from metastatic bone pain, effective palliation of pain becomes an important part of comprehensive therapy formalignant tumors. In this study, we examined the efficacy and safety of the combined regimen of cryoablation and zoledronic acid in patients of bonemetastatic pain. A total of 84 subjects were randomly divided into three groups, and underwent treatments of cryoablation plus zoledronic acid, cryoablation alone, zoledronic acid alone between June 2009 and March 2012. Patients responses had been assessed for a total of 6 months by using the Brief Pain Inventory (BPI)-Short Form. The results showed that the mean response of worst and average pain significantly dropped at week 2 (all P<0.05) in group with cryoablation treatment but at week 4 (all P<0.05) in group with zoledronic acid treatment. While between week 16 and week 24, zoledronic acid treatments showed more durable response to worst and average pain compared to cryoablation (all P<0.05). Cryoablation plus zoledronic acid regimen showed significant drop in worst and average pain between week 1 and week 4 compared to zoledronic acid alone (all P<0.05) and more durable effect on bone metastatic pain between week 12 and week 24 than cryoablation alone (all P<0.05). Additionally, no serious adverse effects and complication were observed by this combination use. In conclusion, cryoablation combined with zoledronic acid was safe and effective regimen and showed its superiority of fast response and durable effect on painful bone metastases.
C1 [Li, Fenqiang] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Wang, Wenhui] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Li, Li] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Chang, Yaowen] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Su, Dongjun] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Guo, Gang] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[He, Xuewen] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
[Li, Mingxiang] Lanzhou University First Hospital, Department of Interventional Radiology, No.1 Donggang West Road, 730000 Lanzhou, China.
RP Wang, W (reprint author), Lanzhou University First Hospital, Department of Interventional Radiology, 730000 Lanzhou, China.
EM wangwenhui1968@163.com
CR Yoh K, Kubota K, Ohmatsu H, Goto K, Niho S, Ohe Y, 2012, Feasibility study of zoledronic acid plus cisplatin-docetaxel as firstline treatment for advanced non-small cell lung cancer with bone metastases. Anticancer Res 32:4131–4135
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de Freitas RM, de Menezes MR, Cerri GG, Gangi A, 2011, Sclerotic vertebral metastases: pain palliation using percutaneous image-guided cryoablation. Cardiovasc Intervent Radiol 34(Suppl 2):S294–S299
Callstrom MR, Charboneau JW, 2007, Image-guided palliation of painful metastases using percutaneous ablation. Tech Vasc Interv Radiol 10:120–131
Paparella S, Finkelberg E, Varisco D, Tondelli E, Rocco F, 2011)Use of zoledronic acid in patients with prostate cancer bone metastases: control of pain and musculoskeletal complications. Urologia 78:300– 304
Yamada K, Yoshimura M, Kaise H, Ogata A, Ueda N, Tokuuye K, Kohno N, 2012, Concurrent use of Sr-89 chloride with zoledronic acid is safe and effective for breast cancer patients with painful bone metastases. Exp Ther Med 3:226–230
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Ottewell PD, Woodward JK, Lefley DV, Evans CA, Coleman RE, Holen I, 2009, Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone. Mol Cancer Ther 8: 2821–2832
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 885
EP 891
DI 10.1007/s12253-014-9769-7
PG 7
ER
PT J
AU Pocza, T
Sebestyen, A
Turanyi, E
Krenacs, T
Mark,
Sticz, BT
Jakab, Zs
Hauser, P
AF Pocza, Timea
Sebestyen, Anna
Turanyi, Eszter
Krenacs, Tibor
Mark, Agnes
Sticz, Bela Tamas
Jakab, Zsuzsanna
Hauser, Peter
TI mTOR Pathway As a Potential Target In a Subset of Human Medulloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Medulloblastoma; mTORC1; mTOR inhibitors; Survival; Daoy; Pediatric; Brain; Tumor; Rapamycin
ID Medulloblastoma; mTORC1; mTOR inhibitors; Survival; Daoy; Pediatric; Brain; Tumor; Rapamycin
AB As mammalian Target of Rapamycin (mTOR) plays role in protein synthesis and metabolism, mTOR pathway activation is involved in the pathogenesis of several types of tumors. Our aim was to elucidate its role in medulloblastoma in terms of prognosis and as a therapeutic target. Members of activated mTOR complex 1 (mTORC1) pathway, phosphomTOR (p-mTOR) and phospho-S6 (p-S6) were examined by immunohistochemistry in formalin fixed paraffin embedded samples of 40 patients with medulloblastoma, and results were compared to clinical features and survival of patients. In proliferation assays, Daoy and UW228–2 medulloblastoma cell lines were tested by rapamycin, an mTORC1 inhibitor, and NVP-BEZ235, a dual mTOR and phosphatidylinositol 3- kinase (PI3K) inhibitor, each in monotherapy and in combination with cytostatic drugs (cisplatin, etoposide). Components of mTORC1 and mTORC2 complexes were also examined in these cell lines. Neither presence of p-mTOR (32.5 %) nor p-S6 (32.5 %) correlated with age, gender or histological subtype. In 22.5 % of cases simultaneous expression of pmTOR and p-S6 was shown. Kaplan-Meier analysis showed inferior survival of patients expressing both marker proteins, but it was not statistically significant, probably due to low case number. UW228–2 cells had greater sensitivity to mTOR inhibitors, possibly due to its higher mTORC1 specific protein expression levels, compared to Daoy cells. In both cell lines antiproliferative effect of cytostatic drugs was significantly enhanced by mTOR inhibitors (p<0.05). Based on our in vitro and clinicopathological studies mTOR inhibitors may have a role in the future treatment of a subset of patients with medulloblastoma.
C1 [Pocza, Timea] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, H-1094 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Turanyi, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Mark, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Sticz, Bela Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Jakab, Zsuzsanna] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, H-1094 Budapest, Hungary.
[Hauser, Peter] Semmelweis University, 2nd Department of Pediatrics, Tuzolto utca 7-9, H-1094 Budapest, Hungary.
RP Hauser, P (reprint author), Semmelweis University, 2nd Department of Pediatrics, H-1094 Budapest, Hungary.
EM hauserpeti@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 893
EP 900
DI 10.1007/s12253-014-9771-0
PG 8
ER
PT J
AU Wrobel, T
Pogrzeba, J
Stefanko, E
Wojtowicz, M
Jazwiec, B
Dzietczenia, J
Mazur, G
Kuliczkowski, K
AF Wrobel, Tomasz
Pogrzeba, Joanna
Stefanko, Ewa
Wojtowicz, Marcin
Jazwiec, Bozena
Dzietczenia, Justyna
Mazur, Grzegorz
Kuliczkowski, Kazimierz
TI Expression of Eph A4, Eph B2 and Eph B4 Receptors in AML
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acutemyeloid leukemia; EphA4-Eph B2-Eph B4; Prognostic impact
ID Acutemyeloid leukemia; EphA4-Eph B2-Eph B4; Prognostic impact
AB Eph receptors represent the largest subfamily of receptor tyrosine kinases (RTKs). The up- regulation of Eph receptors has been documented in various solid tumors, where it often correlates with poor prognosis. Their significance in hematologic malignancies is still unclear. This study aimed to investigate the expression of Eph A4, Eph B2, and Eph B4 mRNA in non - M3 AML patients and determine their prognostic significance. Bone marrow samples from 101 newly diagnosed non -M3 AML patients and 26 healthy controls for comparison were quantified by real time reverse transcriptase polymerase chain reaction (RT-PCR), and the comparative cycle threshold (Ct) method was used to determine their relative expression levels to GUS control gene. The results showed that expression of all selected Eph receptors was significantly lower in AML patients comparing to controls. It also differed according to FAB subtypes. The decreased expression levels of Eph A4 were associated with higher leukocytes (p=0.022) and blast cell counts (p=0.001), and unfavorable FLT3-ITD mutation. Our study revealed significant correlation between lower EphB2 expression levels, and higher complete remission rate (p=0.009724) and longer overall survival. Additionally, we found that patients with shorter RFS had decreased EphB4 expression (p=0.00). In conclusion, the results suggest the prognostic impact of decreased expression levels of some Eph receptors in AML patients.
C1 [Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
[Pogrzeba, Joanna] Regional Hospital in Opole, Department of Hematology, ul. Katowicka 64Opole, Poland.
[Stefanko, Ewa] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
[Wojtowicz, Marcin] Regional Hospital in Opole, Department of Hematology, ul. Katowicka 64Opole, Poland.
[Jazwiec, Bozena] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
[Dzietczenia, Justyna] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
[Mazur, Grzegorz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
[Kuliczkowski, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, L. Pasteura 4 Street, 50-367 Wroclaw, Poland.
RP Pogrzeba, J (reprint author), Regional Hospital in Opole, Department of Hematology, Opole, Poland.
EM joannapog@interia.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 901
EP 907
DI 10.1007/s12253-014-9767-9
PG 7
ER
PT J
AU Kalfert, D
Celakovsky, P
Laco, J
Ludvikova, M
AF Kalfert, David
Celakovsky, Petr
Laco, Jan
Ludvikova, Marie
TI The Role of Protein p16INK4a in Glottic Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laryngeal cancer; Squamous cell carcinoma; p16 protein; Prognostic marker
ID Laryngeal cancer; Squamous cell carcinoma; p16 protein; Prognostic marker
AB Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing the common etiological factors. However some differences in pathogenesis and prognosis of HNSCC have been hitherto documented. Laryngeal squamous cell carcinoma (LSCC) is one the most common type of the head and neck cancer. The majority of laryngeal cancers are located in the glottic area. P16 was recently documented to be important prognostic marker in many tumors including HNSCC. The aim of our study was to assess the significance of p16 expression in glottic LSCC. Fifty eight patients after surgical treatment of the glottic LSCC were enrolled in the retrospective study. The p16 expression was immunohistochemically detected and semiquantitatively evaluated in tumor tissue. The results were statistically correlated with clinical and pathological parameters. Protein p16 was expressed in glottic LSCC of 15 patients (25.9 %). Statistically significant higher p16 overexpression was proven in non-smokers in comparison with smokers (75 % versus 18 %; p =0.003). Recurrent cancer was diagnosed in 8 patients (13.8 %), and all these tumors were p16 negative. Our study shows, that p16 expression in glottic LSCC especially in subgroup of non-smokers might be promising prognosticator of better clinical outcome in routine practice. The p16 status did not statistically correlate with cervical lymph nodemetastases orwith grading and staging of cancers, respectively. The preliminary results suggest that p16 overexpression in glottic LSCC may identify patients at low risk of disease recurrence. However, the pathobiology of this tumor as well as predictive role of p16 expression in laryngeal cancer still remains to be better elucidated.
C1 [Kalfert, David] University Hospital Hradec Kralove, Department of Otorhinolaryngology and Head and Neck SurgeryPrague, Czech Republic.
[Celakovsky, Petr] University Hospital Hradec Kralove, Department of Otorhinolaryngology and Head and Neck SurgeryPrague, Czech Republic.
[Laco, Jan] Charles University, 1st Faculty of Medicine and General Teaching HospitalPrague, Czech Republic.
[Ludvikova, Marie] Charles University in Prague, Faculty of Medicine in Pilsen, Institute of Biology, Karlovarska 48, 30166 Pilsen, Czech Republic.
RP Ludvikova, M (reprint author), Charles University in Prague, Faculty of Medicine in Pilsen, Institute of Biology, 30166 Pilsen, Czech Republic.
EM ludvikova.m@email.cz
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 909
EP 915
DI 10.1007/s12253-014-9773-y
PG 7
ER
PT J
AU Hong, Z
Bi, A
Chen, D
Gao, L
Yin, Z
Luo, L
AF Hong, Zhuan
Bi, Aijing
Chen, Dan
Gao, Li
Yin, Zhimin
Luo, Lan
TI Activation of Hedgehog Signaling Pathway in Human Non-small Cell Lung Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Shh; Ptch-1; Gli-1; Non-small cell lung cancer; Survival
ID Shh; Ptch-1; Gli-1; Non-small cell lung cancer; Survival
AB The activation of the hedgehog pathway, which is an important signaling mechanism crucial in embryogenesis, has strong links to carcinogenesis. Aberrant regulation of this pathway can result in the development of tumors. The present study was designed to investigate Hh related protein expression in non-small cell lung cancers. Fifty five non-small cell lung cancers samples were used in the study. By reverse transcription-polymerase chain reaction (RT-PCR), the expression of Shh, Ptch-1, and Gli-1 in tumor and adjacent normal tissues was examined and associated to clinical pathologic features. The expression levels of Shh, Ptch-1, Gli-1 in non-small cell lung cancer tissues were 63.64, 69.09, 43.64%, respectively, higher than that in the adjacent normal tissues. Survival analysis showed that both Ptch-1 and Gli-1 expression were associated with poor survival (both P<0.05, logrank test). Shh and Ptch-1 expression were correlated with lymph node metastasis. These results suggest that dysregulation of Hh signaling pathway plays an important role in the development of human NSCLCs. The expression of Ptch-1 and Gli-1 is possibly involved in NSCLCs progression, which may be a useful prognostic indicator of NSCLCs.
C1 [Hong, Zhuan] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 22 Hankou Road, 210093 Nanjing, China.
[Bi, Aijing] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 22 Hankou Road, 210093 Nanjing, China.
[Chen, Dan] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 22 Hankou Road, 210093 Nanjing, China.
[Gao, Li] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 22 Hankou Road, 210093 Nanjing, China.
[Yin, Zhimin] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, No. 1 Wenyuan Road, 210046 Nanjing, China.
[Luo, Lan] Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 22 Hankou Road, 210093 Nanjing, China.
RP Luo, L (reprint author), Nanjing Normal University, College of Life Science, Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, 210093 Nanjing, China.
EM lanluo@nju.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 917
EP 922
DI 10.1007/s12253-014-9774-x
PG 6
ER
PT J
AU Kis, A
Tatar, ZsT
Gall, T
Boda, R
Tar, I
Major, T
Redl, P
Gergely, L
Szarka, K
AF Kis, Andrea
Tatar, Zsofia Timea
Gall, Tamas
Boda, Robert
Tar, Ildiko
Major, Tamas
Redl, Pal
Gergely, Lajos
Szarka, Krisztina
TI Frequency of Genetic and Epigenetic Alterations of p14ARF and p16INK4A in Head and Neck Cancer in a Hungarian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell cancer; Laryngeal squamous cell cancer; Tumour suppressor gene; Promoter methylation
ID Oral squamous cell cancer; Laryngeal squamous cell cancer; Tumour suppressor gene; Promoter methylation
AB Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions andmutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher’s exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls (p<0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 (p=0.043 and p=0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.
C1 [Kis, Andrea] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Tatar, Zsofia Timea] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Gall, Tamas] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Boda, Robert] University of Debrecen, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Tar, Ildiko] University of Debrecen, Faculty of Dentistry, Department of Periodontology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Major, Tamas] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Redl, Pal] University of Debrecen, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Gergely, Lajos] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Szarka, Krisztina] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Szarka, K (reprint author), University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, H-4032 Debrecen, Hungary.
EM szkrisz@med.unideb.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 923
EP 929
DI 10.1007/s12253-014-9775-9
PG 7
ER
PT J
AU Ye, Q
Chen, L
Yin, X
Liu, JChY
Ji, Q
Zhao, E
AF Ye, Qingqing
Chen, Li
Yin, Xiaolu
Liu, Jie Charles Yuan
Ji, Qunsheng
Zhao, Enfeng
TI Development of Serous Ovarian Cancer is Associated with the Expression of Homologous Recombination Pathway Proteins
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serous ovarian cancer (SOC); Homologous recombination (HR); Immunohistochemistry (IHC); Meiotic recombination 11 (Mre11); Mediator of DNA damage checkpoint protein 1 (MDC1); Ataxia telangiectasia mutated (ATM); ATM-Rad3-related (ATR); Breast cancer susceptibility gene 1 (BRCA1)
ID Serous ovarian cancer (SOC); Homologous recombination (HR); Immunohistochemistry (IHC); Meiotic recombination 11 (Mre11); Mediator of DNA damage checkpoint protein 1 (MDC1); Ataxia telangiectasia mutated (ATM); ATM-Rad3-related (ATR); Breast cancer susceptibility gene 1 (BRCA1)
AB To investigate the expressions of key markers in the homologous recombination (HR) pathway and the correlation with clinicopathological parameters in serous ovarian cancer (SOC). We analyzed the protein expression of MRE11, MDC1, ATM, ATR and BRCA1 by immunohistochemistry (IHC) in 97 SOC samples, and correlated with clinical parameters including age, tumor grades, clinical stage, status of menstruation and chemotherapy. Low expression of MRE11 and MDC1 was detected in 14.4 % and 3.1 % of the patient samples, and negative expression of ATM, ATR and BRCA1 was found in 11.3 %, 6.3 % and 29.9 % of the patient samples, respectively. ATR deficiency was significantly associated with menopause (P=0.025), strong expression of ATM (P=0.017) and MRE11 (P=0.040) with premenopausal SOC, strong expression of MRE11 (P=0.016) with low tumor grade, and strong expression of BRCA1 (P=0.015) with early clinical stage. In addition, low expression of MRE11 was strongly associated with negativity of ATR (P<0.001) and BRCA1 (P= 0.004) Furthermore, ATR deficiency was associated with low expression of ATM (P=0.028) and loss expression of BRCA1 (P=0.009). Our results suggest that reduced expression or loss of proteins in HR pathway is associated with SOC development. Abnormality of MRE11 and BRCA1 are strongly associated with late clinical stage in SOC patients.
C1 [Ye, Qingqing] AstraZeneca Global R&D, Innovation Center ChinaShanghai, China.
[Chen, Li] Chinese PLA General Hospital, Department of Obstetrics & GynecologyBeijing, China.
[Yin, Xiaolu] AstraZeneca Global R&D, Innovation Center ChinaShanghai, China.
[Liu, Jie Charles Yuan] AstraZeneca Global R&D, Innovation Center ChinaShanghai, China.
[Ji, Qunsheng] AstraZeneca Global R&D, Innovation Center ChinaShanghai, China.
[Zhao, Enfeng] Hainan Branch of Chinese PLA General Hospital, Department of Obstetrics & Gynecology, 572014 Sanya, Hainan, China.
RP Zhao, E (reprint author), Hainan Branch of Chinese PLA General Hospital, Department of Obstetrics & Gynecology, 572014 Sanya, China.
EM 301.zhao@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 931
EP 938
DI 10.1007/s12253-014-9776-8
PG 8
ER
PT J
AU Kovacs, P
Panczel, G
Borbola, K
Juhasz, G
Liszkay, G
AF Kovacs, Peter
Panczel, Gitta
Borbola, Kinga
Juhasz, Gabriella
Liszkay, Gabriella
TI Psychological Changes in Melanoma Patients During Ipilimumab Treatment Compared to Low-Dose Interferon Alpha Therapy—A Follow-Up Study of First Experiences
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ipilimumab; Interferon; Malignant melanoma; Depression; Anxiety
ID Ipilimumab; Interferon; Malignant melanoma; Depression; Anxiety
AB Immuntherapies are frequently accompanied by psychological side effects. Our goals were to detect the changes of psychological factors (depression, anxiety) among melanoma patients during ipilimumab treatment. Ten ipilimumab treated melanoma patients (Group 1.) and 18 low-dose interferon-alpha treated patients (Group 2.) were compared. In our longitudinal study we measured depression (Zung Self- Rating Depression Scale) and anxiety (State-Trait Anxiety Inventory, STAI). Psychological status was tested four times: in every 3 week during ipilimumab treatment according to the relevant treatment protocol and at baseline, 1st, 3rd and 6th month of interferon therapy. No significant differences were detected at different timepoints in the level of depression or in the anxiety scale in Group 1. However significant increase of depression was found in Group 2 during the 6 months of the study. Increased levels of anxiety were found in the second timepoint in both treatment groups. This increase was only temporary and the level of anxiety returned to the baseline. In our sample no measurable psychological differences were detectable during the 12 weeks treatment period of ipilimumab. Ipilimumab seems to have fewer psychological side-effects compared to other immune therapies.
C1 [Kovacs, Peter] National Institute of Oncology, 7-9. Gyorgy Rath Street, 1122 Budapest, Hungary.
[Panczel, Gitta] National Institute of Oncology, 7-9. Gyorgy Rath Street, 1122 Budapest, Hungary.
[Borbola, Kinga] National Institute of Oncology, 7-9. Gyorgy Rath Street, 1122 Budapest, Hungary.
[Juhasz, Gabriella] Semmelweis University, Department of Pharmacology and PharmacotherapyBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, 7-9. Gyorgy Rath Street, 1122 Budapest, Hungary.
RP Kovacs, P (reprint author), National Institute of Oncology, 1122 Budapest, Hungary.
EM kovacs.peter@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 939
EP 944
DI 10.1007/s12253-014-9777-7
PG 6
ER
PT J
AU Powrozek, T
Krawczyk, P
Jarosz, B
Mlak, R
Wojas-Krawczyk, K
Sawicki, M
Stencel, D
Trojanowski, T
Milanowski, J
AF Powrozek, Tomasz
Krawczyk, Pawel
Jarosz, Bozena
Mlak, Radoslaw
Wojas-Krawczyk, Kamila
Sawicki, Marek
Stencel, Dariusz
Trojanowski, Tomasz
Milanowski, Janusz
TI The Application of Real-Time PCR Technique to Detect Rare Cell Clones with Primary T790M Substitution of EGFR Gene in Metastases of Non-small Cell Lung Cancer to Central Nervous System in Chemotherapy Naive Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; EGFR gene; T790M mutation; Metastases to central nervous system; EGFR tyrosine kinase inhibitor
ID Non-small cell lung cancer; EGFR gene; T790M mutation; Metastases to central nervous system; EGFR tyrosine kinase inhibitor
AB The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using realtime PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naive patients.
C1 [Powrozek, Tomasz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Krawczyk, Pawel] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Jarosz, Bozena] Medical University of Lublin, Neurosurgery and Pediatric Neurosurgery DepartmentLublin, Poland.
[Mlak, Radoslaw] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Wojas-Krawczyk, Kamila] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Sawicki, Marek] Medical University of Lublin, Thoracic Surgery DepartmentLublin, Poland.
[Stencel, Dariusz] Boehringer Ingelheim PolandWarsaw, Poland.
[Trojanowski, Tomasz] Medical University of Lublin, Neurosurgery and Pediatric Neurosurgery DepartmentLublin, Poland.
[Milanowski, Janusz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
RP Krawczyk, P (reprint author), Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, 20-954 Lublin, Poland.
EM krapa@poczta.onet.pl
CR Zhou W, Ercan B, Janne PA, Gray NS, 2011, Discovery of selective irreversible inhibitors for EGFR-T790M. Bioorg Med Chem Lett 21(2):638–643
Ma C, Wei S, Song Y, 2011, T790M and acquired resistance of EGFRTKI: a literature review of clinical reports. J Thorac Dis 3:10– 18
Krawczyk P, Mlak R, Powrozek T, Nicos M, Kowalski DM, Wojas- Krawczyk K et al, 2012, Mechanisms of resistance to reversible inhibitors of EGFR tyrosine kinase in non-small cell lung cancer. Wspolczesna Onkol 16(5):401–406
Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CVet al, 2008, Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359:366–377
Su K-Y, Chen H-Y, Li K-C, Kuo M-L, Yang JC-H, Chan W-K et al, 2012, Pretreatment epidermal growth factor receptor, EGFR, T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non–small-cell lung cancer. J Clin Oncol 30:433–440
Oh JE, An CH, Yoo NJ, Lee SH, 2011, Detection of low-level EGFR T790M mutation in lung cancer tissues. APMIS 119(7):403–411
Asano H, Toyooka S, Tokumo M, Ichimura K, Aoe K, Ito S et al, 2006, Detection of EGFR gene mutation in lung cancer by mutantenriched polymerase chain reaction assay. Clin Cancer Res 12:43–48
Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al, 2006, Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 119(6):1491–1494
Han HS, Eom DW, Kim JH, Kim KH, Shin HM, An JYet al, 2011, EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer 12(6):380–386
Inukai M, Toyooka S, Ito S, Asano H, Ichihara S, Soh J et al, 2006, Presence of epidermal growth factor receptor gene T790M mutation as aminor clone in non–small cell lung cancer. Cancer Res 66:7854–7858
Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW et al, 2012, Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy, LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 13(5):528–538
Hirsh V, Cadranel J, Cong XJ, Fairclough D, Finnern HW, Lorence RM et al, 2013, Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial, LUXLung 1). J Thorac Oncol 8(2):229–237
Janjigian YY, Groen HJ, Horn L, Smit EF, Fu Y,Wang F et al., 2011, Activity and tolerability of afatinib, BIBW 2992, and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib. J Clin Oncol 29(suppl): abstr 7525
Fujita Y, Suda K, Kimura H, Matsumoto K, Arao T, Nagai T et al, 2012, Highly sensitive detection of EGFR T790M mutation using colony hybridization predicts favorable prognosis of patients with lung cancer harboring activating EGFR mutation. J Thorac Oncol 7(11):1640–1644
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 945
EP 951
DI 10.1007/s12253-014-9778-6
PG 7
ER
PT J
AU Ding, W
Wang, G
Shao, K
Wang, F
Huang, H
Ju, Sh
Cong, H
Wang, H
AF Ding, Weifeng
Wang, Guihua
Shao, Keke
Wang, Feng
Huang, Hua
Ju, Shaoqing
Cong, Hui
Wang, Huimin
TI Amelioration of Colorectal Cancer Using Negative Lipidoid Nanoparticles to Encapsulate siRNA Against APRIL by Enema Delivery Mode
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; A proliferation-inducing ligand; Negative lipidoid nanoparticles; siRNA; Enema; Small-molecule drugs
ID Colorectal cancer; A proliferation-inducing ligand; Negative lipidoid nanoparticles; siRNA; Enema; Small-molecule drugs
AB A proliferation-inducing ligand (APRIL) is a key cell proliferation-regulatory molecule and have been investigated well enough in immunity regulation and a few of immune diseases. APRIL can stimulate tumor cell growth and is up-expressed in cancer tissues, especially in CRC (colorectal cancer). However, whether inhibition of APRIL can regulate tumor-relative genes expression in vivo and subsequently ameliorate the pathological progress of CRC remains obscure. To address this question, we developed a novel negative lipidoid nanoparticles (NLNs) encapsulating small interference RNA (siRNA) for selectively silencing APRIL in the parenchyma of CRC focus in vivo, which uptake proceeded through a lipid raft endocytotic pathway. Local enema delivery of APRIL-NLNs silenced APRIL in CRC cells and animal models, and then ameliorated experimentally the progress of CRC by suppressing CRC cell proliferation, metastasis, and apoptosis-related cytokine expression and did not affect the function of liver and kidneys and not trigger the immune response of CRC models. This study reveals APRIL to be a potential anti-CRC target by in vivo experiments, and suggests that the application of similar modes of siRNA delivery may be feasible in other therapeutic settings.
C1 [Ding, Weifeng] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
[Wang, Guihua] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
[Shao, Keke] The First People’s Hospital of Yancheng City, Medical Laboratory DepartmentYancheng, Jiangsu Province, China.
[Wang, Feng] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
[Huang, Hua] Affiliated Hospital of Nantong University, Pathology Medicine CenterNantong, Jiangsu Province, China.
[Ju, Shaoqing] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
[Cong, Hui] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
[Wang, Huimin] Affiliated Hospital of Nantong University, Department of Laboratory MedicineNantong, Jiangsu Province, China.
RP Cong, H (reprint author), Affiliated Hospital of Nantong University, Department of Laboratory Medicine, Nantong, China.
EM dwfnt@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 953
EP 964
DI 10.1007/s12253-014-9779-5
PG 12
ER
PT J
AU Choi, JY
Kim, SM
An, HCh
Yoo, JN
Lee, HS
AF Choi, Jin Youn
Kim, Sung Min
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Regional Bias of Intratumoral Genetic Heterogeneity of Nucleotide Repeats in Colon Cancers with Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bethesda panel; Colorectal cancer; Dinucleotide repeats; Intratumoral heterogeneity; Microsatellite instability; Mononucleotide repeats; Promega panel
ID Bethesda panel; Colorectal cancer; Dinucleotide repeats; Intratumoral heterogeneity; Microsatellite instability; Mononucleotide repeats; Promega panel
AB Intratumoral heterogeneity (ITH) may produce regional biases in genotype and phenotype evaluation in a single tumor and may impede proper cancer diagnosis. To evaluate the extent of ITH in colorectal cancer (CRC) with microsatellite instability (MSI), we obtained 4–7 biopsies from39CRCs followed by MSI analysis either using the Bethesda MSI evaluation system or Promega system with 5 mononucleotide markers. We found decreased prevalence of MSI (+) by the Promega system compared to the Bethesda system. The overall discordance between the two systems was 54%. In contrast to the previous studies that had shown discordance only in low MSI (MSI-L), our results showed the discordance not only in MSI-L, but also in high MSI (MSI-H) cases. Among the MSI (+) CRCs, ITH of MSI status was identified in 41.7%of CRC by the Bethesda systemand 22.2%by the Promega system. In terms of MSI markers, the ITH originated from dinucleotide markers in most cases (69 %), but it originated from mononucleotide markers (31 %) as well. Pooling of DNA from a regional biopsy with MSI (+) with additional biopsies from stable MSI (MSS) showed that this approach was beneficial to increase the sensitivity of MSI detection. Our results indicate that ITH of MSI phenotype by the Bethesda system is more overestimated than previously identified. However, because there was considerable ITH of MSI subtypes and markers even by the Promega system, our data suggest that analysis of MSI status in multiple regional biopsies is needed for a better evaluation of MSI status in CRC.
C1 [Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General Surgery, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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Xicola RM, Llor X, Pons E, Castells A, Alenda C, Pinol V, Andreu M, Castellvi-Bel S, Paya A, Jover R, Bessa X, Giros A, Duque JM, Nicolas-Perez D, Garcia AM, Rigau J, Gassull MA; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association, 2007, Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst 99:244–52
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Fallik D, Borrini F, Boige V, Viguier J, Jacob S, Miquel C, Sabourin JC, Ducreux M, Praz F, 2003)Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 63:5738–44
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 965
EP 971
DI 10.1007/s12253-014-9781-y
PG 7
ER
PT J
AU Sari, E
Nagy, GyZs
Baghy, K
Rajnai, H
Bodor, Cs
Csomor, J
Barna, G
Rudas, G
Kovalszky, I
Demeter, J
AF Sari, Eszter
Nagy, Gyorgy Zsolt
Baghy, Kornelia
Rajnai, Hajnalka
Bodor, Csaba
Csomor, Judit
Barna, Gabor
Rudas, Gabor
Kovalszky, Ilona
Demeter, Judit
TI Treatment of Refractory Hairy Cell Leukemia with a BRAF-inhibitor: Lessons to be Learnt
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hairy cell leukemia; Refractory; BRAF V600E; Vemurafenib
ID Hairy cell leukemia; Refractory; BRAF V600E; Vemurafenib
AB Hairy cell leukemia is a rare chronic lymphoproliferative disorder with indolent but progressive clinical course. Patients require treatment when they have significant cytopenia or recurrent infections. The gold standard treatment are purine nucleoside analogues (cladribine and pentostatine), with these agents the rate of complete remission can approach even 95 %. The differential diagnosis between classical hairy cell leukemia and other, rare splenic lymphomas that can mimic this disease might be really challenging. Splenic lymphoma with villous lymphocytes and other new, provisional WHO entities share some, but not all immunophenotypical features with hairy cell leukemia. The correct diagnosis is of an extreme importance as these entities require different treatment. Thus further investigation in the pathogenesis of hairy cell leukemia is required in order to solve this challenge. Discovery of the BRAF V600E mutation as a diseasedefining genetic event in hairy cell leukemia can be helpful in both differential diagnosis and treatment of this disease.We report the case of three hairy cell leukemia patients, whose diagnosis or treatment was based on this newly discovered somatic mutation, but the treatment results and side effects were individual.
C1 [Sari, Eszter] Semmelweis University, 1st Department of Internal Medicine, Koranyi S. Str. 2/a, H-1083 Budapest, Hungary.
[Nagy, Gyorgy Zsolt] Semmelweis University, 1st Department of Internal Medicine, Koranyi S. Str. 2/a, H-1083 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Rajnai, Hajnalka] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Rudas, Gabor] Semmelweis Egyetem, MR Kutatokozpont, Balassa Str. 6, H-1083 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Str. 26, H-1085 Budapest, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal Medicine, Koranyi S. Str. 2/a, H-1083 Budapest, Hungary.
RP Demeter, J (reprint author), Semmelweis University, 1st Department of Internal Medicine, H-1083 Budapest, Hungary.
EM demjud@bel1.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 973
EP 980
DI 10.1007/s12253-014-9783-9
PG 8
ER
PT J
AU Ladanyi, A
Sebestyen, T
Mohos, A
Liszkay, G
Somlai, B
Toth, E
Timar, J
AF Ladanyi, Andrea
Sebestyen, Timea
Mohos, Anita
Liszkay, Gabriella
Somlai, Beata
Toth, Erika
Timar, Jozsef
TI Ectopic lymphoid structures in primary cutaneous melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ectopic lymphoid structures; Primary melanoma; B cells; T cells; Follicular dendritic cells; High endothelial venules
ID Ectopic lymphoid structures; Primary melanoma; B cells; T cells; Follicular dendritic cells; High endothelial venules
AB Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO+ memory T cells. A network of CD21+ follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79+ HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures. The appearance of B-cell aggregates did not show association with the outcome of the disease, although a trend for their higher prevalence was observed in thicker tumors. Our results show that neogenesis of lymphoid structures does occur in primary melanomas, albeit with lower frequency compared to that reported in metastases.
C1 [Ladanyi, Andrea] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, 7-9. Rath Gyorgy u., H-1122 Budapest, Hungary.
[Sebestyen, Timea] St John's Hospital, Department of Pathology, 1-3. Dios arok, H-1125 Budapest, Hungary.
[Mohos, Anita] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 26. Ulloi ut, H-1085 Budapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gyorgy u., H-1122 Budapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 41. Maria u, H-1085 Budapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, 7-9. Rath Gyorgy u., H-1122 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, 93. Ulloi ut, H-1091 Budapest, Hungary.
RP Ladanyi, A (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, H-1122 Budapest, Hungary.
EM ladanyi@oncol.hu
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van Baren N, Baurain JF, Coulie PG, 2013, Lymphoid neogenesis in melanoma. What does it tell us? OncoImmunology 2:e22505
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 981
EP 985
DI 10.1007/s12253-014-9784-8
PG 5
ER
PT J
AU Zhang, Y
Liu, H
Chen, X
Bai, Q
Liang, R
Shi, B
Liu, L
Tian, D
Liu, M
AF Zhang, Yongqing
Liu, Hongjuan
Chen, Xiequn
Bai, Qingxian
Liang, Rong
Shi, Bing
Liu, Lihui
Tian, DengMei
Liu, Mingjuan
TI Modified Bortezomib, Adriamycin and Dexamethasone (PAD) Regimen in Advanced Multiple Myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Modified PAD regimen; Bortezomib; Advanced multiple myeloma; Efficacy and safety
ID Modified PAD regimen; Bortezomib; Advanced multiple myeloma; Efficacy and safety
AB The PAD regime, composed of bortezomib, adriamycin and dexamethasone, improves the outcomes of patients with advanced multiple myeloma (MM), but at the same time produces high frequency of serious toxic side effects. For the first time, we evaluated the efficacy and safety of a bortezomib-dose-reduced PAD regime in the treatment of relapsed/refractory MM in this clinical study. Forty-five patients were treated with two to six 21-day cycles of PAD, comprising bortezomib at 1.3 mg/m2 (P1AD, n=21) or 1.0 mg/m2 (P2AD, n=24) (days 1, 4, 8, 11), adriamycin at 9 mg/m2 (days 1–4) and dexamethasone at 40 mg/day (days 1–4). Overall, 36 patients (80 %) showed at least partial remission (PR), in which 9 cases (20 %) showed complete remission (CR) and 10 cases (22 %) showed very good partial remission (VGPR). The efficacy of PAD regimen in advanced MM patients was not related to the traditional prognostic factors. There was no significant difference between P1AD and P2AD in the rates of PR, CR or VGPR, 1.5-year progression-free survival (PFS), and overall survival (OS) (81 % vs. 79%, 48 % vs. 38%, 64% vs. 59%, and 85% vs. 73 %, respectively). However, the grade 3–4 toxic effects, including thrombocytopenia (13 % vs. 38 %), peripheral neuropathy (8 % vs. 33%) and 3–4 grade gastrointestinal reaction (13%vs. 43%), were markedly inhibited after P2AD compared to P1AD (P<0.05). The bortezomib-dose-reduced PAD regime reduced the incidence of adverse reactions without affecting the treatment efficacy in patients with advanced MM.
C1 [Zhang, Yongqing] the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 17 Heishanhu Road, 100091 Beijing, China.
[Liu, Hongjuan] the 309th Hospital of Chinese People’s Liberation Army, Department of Geriatrics, 100091 Beijing, China.
[Chen, Xiequn] the Fourth Military Medical University, Xijing Hospital, Department of Hematology, 710032 Xi’an, China.
[Bai, Qingxian] the Fourth Military Medical University, Xijing Hospital, Department of Hematology, 710032 Xi’an, China.
[Liang, Rong] the Fourth Military Medical University, Xijing Hospital, Department of Hematology, 710032 Xi’an, China.
[Shi, Bing] the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 17 Heishanhu Road, 100091 Beijing, China.
[Liu, Lihui] the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 17 Heishanhu Road, 100091 Beijing, China.
[Tian, DengMei] the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 17 Heishanhu Road, 100091 Beijing, China.
[Liu, Mingjuan] the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 17 Heishanhu Road, 100091 Beijing, China.
RP Zhang, Y (reprint author), the 309th Hospital of Chinese People’s Liberation Army, Department of Hematology, 100091 Beijing, China.
EM zhangyongqing0725@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2014
VL 20
IS 4
BP 987
EP 995
DI 10.1007/s12253-014-9785-7
PG 9
ER
PT J
AU Sulyok, M
Makara, M
Ujhelyi, E
Valyi-Nagy, I
AF Sulyok, Mihaly
Makara, Mihaly
Ujhelyi, Eszter
Valyi-Nagy, Istvan
TI Non-Hodgkin Lymphoma and Hepatitis C: Where We are and What Next?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Hepatitis C; Cryoglobulinemia; Non-Hodgkin lymphoma; Direct acting antivirals; Interferon
ID Hepatitis C; Cryoglobulinemia; Non-Hodgkin lymphoma; Direct acting antivirals; Interferon
AB The association between hepatitis C virus and certain B-cell non-Hodgkin lymphomas, such as marginal zone lymphomas, is supported by epidemiological studies. The exact pathogenetic mechanism is still unknown but both chronic antigenic stimulation and viral lymphotropism may contribute to the evolution of the malignant clone. Furthermore, the hematologic response following hepatitis C antiviral treatment suggests that the virus may have an etiologic role. Interferon and ribavirin based treatment proved to be successful in small case series of hepatitis C virus associated splenic lymphoma with villous lymphocytes, therefore, it is suggested that antiviral treatment could be an alternative to chemo-immunotherapy. In the near future new more potent direct acting antivirals will make interferon free treatments possible. It is still an open question whether these new shortcourse regimens are also effective in the treatment of associated lymphomas and what is the importance of the lymphoid reservoir in eliminating HCV.
C1 [Sulyok, Mihaly] St. Istvan and St Laszlo Hospital, Hepatology Center, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Makara, Mihaly] St. Istvan and St Laszlo Hospital, Hepatology Center, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Ujhelyi, Eszter] St. Istvan and St Laszlo Hospital, Immunology LaboratoryBudapest, Hungary.
[Valyi-Nagy, Istvan] St. Istvan and St Laszlo Hospital, Hepatology Center, Albert Florian str. 5-7, 1097 Budapest, Hungary.
RP Sulyok, M (reprint author), St. Istvan and St Laszlo Hospital, Hepatology Center, 1097 Budapest, Hungary.
EM sulyok.mihaly@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 1
EP 7
DI 10.1007/s12253-014-9845-z
PG 7
ER
PT J
AU Sikalidis, KA
AF Sikalidis, K Angelos
TI Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE T-cell; Amino acids; Cysteine; Glutamine; Phenylalanine; Tryptophan; Arginine; Immune response; Signaling; Immunomodulation; Avidity
ID T-cell; Amino acids; Cysteine; Glutamine; Phenylalanine; Tryptophan; Arginine; Immune response; Signaling; Immunomodulation; Avidity
AB While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing mechanisms not completely delineated. Interesting work has investigated how certain amino acids affect the proliferation rate of T-cells as well as their effectiveness in clearing tumors. The role of amino acids cysteine, glutamine, phenylalanine, tryptophan and arginine in immunomodulation and particularly regarding T-cell proliferation and activation is discussed. The redox balance is reported to affect T-cell proliferation via modulation of cysteine availability. In addition antigen presenting cells (APCs), similar to myeloid cells determine the availability of amino acids in the extracellular microenvironment affecting T-cell proliferation and activation. A better mechanistic understanding of T-cell function modulation via amino acid signaling or metabolic properties may be helpful towards optimization of adaptive immunity with implications for cancer prognosis and treatment.
C1 [Sikalidis, K Angelos] Harvard Medical School, Harvard Institutes of Medicine, Dana-Farber Cancer Institute, Immunobiology Laboratory, 77Avenue Louis Pasteur, 02115 Boston, MA, USA.
RP Sikalidis, KA (reprint author), Harvard Medical School, Harvard Institutes of Medicine, Dana-Farber Cancer Institute, Immunobiology Laboratory, 02115 Boston, USA.
EM angelos_sikalidis@dfci.harvard.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 9
EP 17
DI 10.1007/s12253-014-9860-0
PG 9
ER
PT J
AU Wang, XT
Li, DG
Li, L
Kong, FB
Pang, LM
Mai, W
AF Wang, Xiao-Tong
Li, De-Gang
Li, Lei
Kong, Fan-Biao
Pang, Li-Ming
Mai, Wei
TI Meta-Analysis of Oncological Outcome After Abdominoperineal Resection or Low Anterior Resection for Lower Rectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Low anterior resection; Abdominoperineal resection; Lower rectal cancer; Prognosis
ID Low anterior resection; Abdominoperineal resection; Lower rectal cancer; Prognosis
AB In lower rectal cancer, postoperative outcome is still subject of controversy between the advocates of abdominoperineal resection (APR) and low anterior resection (LAR). Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. Publications were identified which assessed the differences comparing 5- year survival, local recurrence, circumferential resection margin rate, complications and so on. A meta-analysis was performed to clarify the safety and feasibility of the two procedures with several types of outcome measures. A total of 13 studies met the inclusion criteria, and comprised 6,850 cases. Analysis of these data showed that LAR group was highly correlated with 5-year survival (pooled OR=1.73, 95%CI: 1.30–2.29, P=0.0002 random-effect). And local recurrence rate of APR group was significantly higher than that in LAR group (pooled OR=0.63, 95%CI: 0.53–0.75, P<0.00001 fixed-effect). Also, the circumferential resection margin (CRM) were high involved in APR group than in LAR group. (5 trials reported the data, pooled OR=0.43, 95%CI: 0.36– 0.52, P<0.00001 fixed-effect). Besides, the incidents of overall complications of APR group was higher compared with LAR group (pooled OR=0.52, 95%CI: 0.29–0.92, P=0.03 random-effect). Patients treated by APR have a higher rate of CRM involvement, a higher local recurrence, and poorer prognosis than LAR. And there is evidence that in selected low rectal cancer patients, LAR can be used safely with a better oncological outcome than APR. due to the inherent limitations of the present study, for example, the trails available for this systematic review are limited and the finite retrospective data, future prospective randomized controlled trials will be useful to fully investigate these outcome measures and to confirm this conclusion.
C1 [Wang, Xiao-Tong] People’s Hospital of Guangxi Zhuang Autonomous Region, Departments of Gastrointestinal and Peripheral Vascular SurgeryNanning, China.
[Li, De-Gang] The First Affiliated Hospital of Guangxi University of Chinese Medicine, Departments of SurgeryNanning, China.
[Li, Lei] People’s Hospital of Guangxi Zhuang Autonomous Region, Departments of Gastrointestinal and Peripheral Vascular SurgeryNanning, China.
[Kong, Fan-Biao] The First Affiliated Hospital of Guangxi University of Chinese Medicine, Departments of SurgeryNanning, China.
[Pang, Li-Ming] The First Affiliated Hospital of Guangxi University of Chinese Medicine, Departments of SurgeryNanning, China.
[Mai, Wei] People’s Hospital of Guangxi Zhuang Autonomous Region, Departments of Gastrointestinal and Peripheral Vascular SurgeryNanning, China.
RP Mai, W (reprint author), People’s Hospital of Guangxi Zhuang Autonomous Region, Departments of Gastrointestinal and Peripheral Vascular Surgery, Nanning, China.
EM 13977154858@139.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 19
EP 27
DI 10.1007/s12253-014-9863-x
PG 9
ER
PT J
AU Kiss, O
Tokes, AM
Spisak, S
Szilagyi, A
Lippai, N
Szekely, B
Szasz, AM
Kulka, J
AF Kiss, Orsolya
Tokes, Anna-Maria
Spisak, Sandor
Szilagyi, Anna
Lippai, Norbert
Szekely, Borbala
Szasz, Attila Marcell
Kulka, Janina
TI Breast- and Salivary Gland-Derived Adenoid Cystic Carcinomas: Potential Post-Transcriptional Divergencies. A Pilot Study Based on miRNA Expression Profiling of Four Cases and Review of the Potential Relevance of the Findings
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenoid cystic carcinoma; microRNA; Breast; Salivary gland
ID Adenoid cystic carcinoma; microRNA; Breast; Salivary gland
AB Adenoid cystic carcinoma (ACC) is a malignant tumor of the salivary glands but identical tumors can also arise from the breast. Despite their similar histomorphological appearance the salivary gland- and the breast-derived forms differ in their clinical features: while ACC of the salivary glands (sACC) have an agressive clinical course, the breastderived form (bACC) shows a very favourable clinical outcome. To date no exact molecular alterations have yet been identified which would explain the diverse clinical features of the ACCs of different origin. In our pilot experiment we investigated the post-transcriptional features of ACC cases by performing microRNA-profiling on 2-2 bACC and sACC tissues and on 1-1 normal breast and salivary gland tissue. By comparing the microRNA-profiles of the investigated samples we identified microRNAs which were expressed differently in bACC and sACC cases according to their normal controls: 7 microRNAs were overexpressed in sACC cases and downexpressed in bACC tumors (let-7b, let-7c, miR-17, miR-20a, miR-24, miR-195, miR-768-3) while 9 microRNAs were downexpressed in sACC cases and overexpressed in bACC tissues (let-7e, miR-23b, miR-27b, miR-193b, miR-320a, miR-320c, miR-768-5p, miR-1280 and miR-1826) relative to their controls. We also identified 8 microRNAs which were only expressed in sACCs and one microRNA (miR-1234) which was only absent in sACC cases. By target predictor online databases potential targets of the these microRNAs were detected to identify genes that may play central role in the diverse cinical outcome of bACC and sACC cases.
C1 [Kiss, Orsolya] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tokes, Anna-Maria] Hungarian Academy of Sciences, MTA-SE Tumor Progression Research GroupBudapest, Hungary.
[Spisak, Sandor] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Szilagyi, Anna] Fejer County Szent Gyorgy HospitalSzekesfehervar, Hungary.
[Lippai, Norbert] Jasz-Nagykun-Szolnok County Hetenyi Geza HospitalSzolnok, Hungary.
[Szekely, Borbala] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szasz, Attila Marcell] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kulka, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM kulka.janina@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 29
EP 44
DI 10.1007/s12253-014-9770-1
PG 16
ER
PT J
AU Zhang, G
Liu, X
Huang, W
Li, X
Johnstone, M
Deng, Y
Ke, Y
Nunes, MQ
Wang, H
Wang, Y
Zhang, X
AF Zhang, Guanjun
Liu, Xi
Huang, Wei
Li, Xiaofeng
Johnstone, Marianne
Deng, Yuan
Ke, Yongqiang
Nunes, M Quentin
Wang, Hongyan
Wang, Yili
Zhang, Xuebin
TI Carcinoma Showing Thymus-Like Elements of the Thyroid Gland: Report of Three Cases Including One Case with Breast Cancer History
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoma showing thymus-like elements; Breast cancer; Second primary tumor; Solid cell nests; Differential diagnosis; Histogenesis
ID Carcinoma showing thymus-like elements; Breast cancer; Second primary tumor; Solid cell nests; Differential diagnosis; Histogenesis
AB Carcinoma showing thymus-like elements (CASTLE) is a raremalignant tumor of the thyroid or adjacent neck soft tissues, whose histogenesis is still debated. It may resemble other primary or metastatic poorly differentiated tumors histologically and the differential diagnosis is crucial for CASTLE has a better prognosis. However, CASTLE as a second primary tumor has not been reported in the literature. We report three cases of thyroid CASTLE, including a unique tumor following breast-conserving surgery for early-stage breast invasive carcinoma. There were two female and one male. All three tumors were located in the right lobe of the thyroid, and one tumor showed extension into the surrounding soft tissue. Histologically, all tumors showed expansive growth and consisted of cords, nests or sheets of epithelial cells divided into irregularly shaped lobules by fibrous connective tissue with lymphoplasmacytic infiltration. Focal squamous differentiation resembling Hassall’s corpuscles were observed. All cases stained positively for CD5, CD117, high molecular weight cytokeratin, cytokeratin, P63, carcinoembryonic antigen and epithelial membrane antigen. Positive staining for Bcl-2 in two cases and chromogranin A in one case was noted. Ki-67 expression ranged from 15 to 25 %. Thyroid transcription factor and CD3 were negative. There was no evidence of recurrent or metastatic disease at following surgery. These features demonstrated CASTLE may arise from branchial pouch remnants, the thyroid solid cell nests. CASTLE is a rare entity, awareness of its occurrence as a second primary tumor is important to avoid overtreatment because it is associated with a favorable prognosis.
C1 [Zhang, Guanjun] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Liu, Xi] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Huang, Wei] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Li, Xiaofeng] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Johnstone, Marianne] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Deng, Yuan] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Ke, Yongqiang] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Nunes, M Quentin] Royal Liverpool University Hospital, Division of Surgery and OncologyLiverpool, UK.
[Wang, Hongyan] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Wang, Yili] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
[Zhang, Xuebin] Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
RP Liu, X (reprint author), Medical College of Xian Jiaotong University, First Affiliated Hospital, Department of Pathology, 710061 Xi’an, China.
EM liuxizgq@gmail.com
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Liu Z, Teng XY, Sun DX, Xu WX, Sun SL, 2013, Clinical Analysis of Thyroid Carcinoma Showing Thymus-Like Differentiation: Report of 8 Cases. Int Surg 98:95–100
Tsutsui H, Hoshi M, Kubota M, Suzuki A, Nakamura N, Usuda J, Shibuya H,Miyajima K, Ohira T, Ito K, Ikeda N, 2013)Management of Thyroid Carcinoma Showing Thymus-Like Differentiation, CASTLE, Invading the Trachea. Surg Today., DOI 10.1007/s00595- 013-0560-2
Cheuk W, Chan JKC, Dorfman DM, Giordano T, 2004, Carcinoma Showing Thymus-Like Differentiation. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, eds, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs, 3rd edn. IARC Press, Lyon, pp 96–97
Torres-Cabala CA,WangWL, Trent J, Yang D, Chen S, Galbincea J, Kim KB, Woodman S, Davies M, Plaza JA, Nash JW, Prieto VG, Lazar AJ, Ivan D, 2009, Correlation Between KIT Expression and KITMutation inMelanoma: A Study of 173 Cases with Emphasis on the Acral-Lentiginous/Mucosal Type. Mod Pathol 22:1446–1456
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, 2012, WHO Classification of Tumours of the Breast, 4th edn. IARC Press, Lyon
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Dorfman DM, Shahsafaei A, Miyauchi A, 1998, Intrathyroidal Epithelial Thymoma, ITET)/Carcinoma Showing Thymus-Like Differentiation, CASTLE, Exhibits CD5 Immunoreactivity: new Evidence for Thymic Differentiation. Histopathology 32:104–109
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Cameselle-Teijeiro J, Abdulkader I, Perez-Becerra R, Vazquez- Boquete A, Alberte-Lista L, Ruiz-Ponte C, Forteza J, Sobrinho- Simoes M, 2009, BRAF Mutation in Solid Cell Nest Hyperplasia Associated with Papillary Thyroid Carcinoma. A Precursor Lesion? Hum Pathol 40:1029–1035
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 45
EP 51
DI 10.1007/s12253-014-9772-z
PG 7
ER
PT J
AU Ottoffy, G
Szigeti, E
Bartyik, K
Nyari, Cs
Parker, L
McNally, JQR
Nyari, AT
AF Ottoffy, Gabor
Szigeti, Erika
Bartyik, Katalin
Nyari, Csaba
Parker, Louise
McNally, J Q Richard
Nyari, Andras Tibor
TI Investigating the Relationship between Mortality from Respiratory Diseases and Childhood Acute Lymphoblastic Leukaemia in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Childhood acute lymphoblastic leukaemia; Gender-specific difference; Deaths from respiratory infections; Poisson regression
ID Childhood acute lymphoblastic leukaemia; Gender-specific difference; Deaths from respiratory infections; Poisson regression
AB Our aim was to investigate the ecological association between death from infectious disease of the respiratory system and the risk of acute lymphoid leukaemia (ALL) in children aged less than 7 years. Poisson regression analyses were carried out using overall data and gender-specific models. The study included 176 cases (92(52.3 %) boys and 84 (47.7 %) girls) of ALL in those aged 0–6 years in South Hungary. Eight cases were diagnosed before the age of 1 year. A significant risk of ALL disease was observed with higher levels of mortality from the chronic respiratory diseases (p=0.035) and pneumonia (p=0.010) among children aged 2–5 years (Odds Ratio for trend was 1.001 and 95%CI [1.000–1.002] and Odds ratio for trend was 1.013 and 95%CI [1.003–1.023], respectively). Significantly increased risk of childhood ALL was detected among children under 1 year of age residing in areas around birth with higher levels of mortality from influenza (Odds Ratio (OR) for trend was 1.05; 95%CI [1.01–1.09]; p=0.012). This risk was also detected in girls (p<0.001), but not in boys (p=0.43). Our findings provide new evidence that will help to understand the different pattern of female and male childhood ALL occurrence , but further studies are needed using detailed individual medical history to clarify the role of influenza and other infectious diseases in the etiology of childhood ALL and to explain gender-specific effects.
C1 [Ottoffy, Gabor] University of Pecs, Department of PediatricsPecs, Hungary.
[Szigeti, Erika] University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
[Bartyik, Katalin] University of Szeged, Department of PediatricsSzeged, Hungary.
[Nyari, Csaba] Saint Stephen University, Faculty of Economics, Agriculture and Health StudiesBekescsaba, Hungary.
[Parker, Louise] Dalhousie University, IWK Health Centre, Department of PediatricsHalifax, Canada.
[McNally, J Q Richard] Newcastle University, Institute of Health and SocietyNewcastle upon Tyne, UK.
[Nyari, Andras Tibor] University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
RP Nyari, AT (reprint author), University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
EM nyari.tibor@med.u-szeged.hu
CR Kinlen LJ, 1995, Epidemiological evidence for an infective basis in childhood leukaemia. Br J Cancer 71:1–5
McNally RJQ, Eden TOB, 2004, An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol 127: 243–263
Hakulinen T, Hovi L, Karkinen-Jaaskelainen, Penttinen K, Saxen L, 1973, Association between influenza during pregnancy and childhood leukaemia. Br Med J 4(5887):265–267
Bithell JF, Draper GJ, Gorbach PD, 1973, Association between malignant disease in children and maternal virus infections. Br Med J 1(5855):706–708
Randolph VL, Heath CW Jr, 1974, Influenza during pregnancy in relation to subsequent childhood leukemia and lymphoma. Am J Epidemiol 100(5):399–409
Curnen MG, Varma AA, Christine BW, Turgeon LR, 1974, Childhood leukemia and maternal infectious diseases during pregnancy. J Natl Cancer Inst 53(4):943–947
Kwan ML, Metayer C, Crouse V, Buffler PA, 2007, Maternal illness and drug/medication use during the period surrounding pregnancy and risk of childhood leukemia among offspring. Am J Epidemiol 165(1):27–35
Parodi S, Santi I,Marani E et al, 2012, Infectious diseases and risk of leukemia and non-Hodgkin’s lymphoma: a case–control study. Leuk Res 36:1354–1358
Nyari TA, Dickinson HO, Parker L, 2003, Childhood cancer in relation to infections in the community during pregnancy and around the time of birth. Int J Cancer 104(6):772–777
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Nyari TA, Kajtar P, Bartyik K, Thurzo L, McNally R, Parker L, 2008, Seasonal variation of childhood acute lymphoblastic leukaemia is different between girls and boys. Pathol Oncol Res 14: 423–428
Nyari TA, Kajtar P, Bartyik K, Thurzo L, Parker L, 2006, Childhood acute lymphoblastic leukaemia in relation to population mixing around the time of birth in South Hungary. Pediatr Blood Cancer 47: 944–948
Nyari TA, Ottoffy G, Bartyik K et al, 2013, Spatial clustering of childhood acute lymphoblastic leukaemia in Hungary. Pathol Oncol Res 19:297–302
Cotterill SJ, Parker L, Malcolm AJ, Reid M, More L, Craft AW, 2000, Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry. Br J Cancer 83: 397–403
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 53
EP 57
DI 10.1007/s12253-014-9786-6
PG 5
ER
PT J
AU Girardi, MF
Barra, BM
Zettler, GC
AF Girardi, Muradas Fabio
Barra, Bizarro Marinez
Zettler, Galleano Claudio
TI Predictive Factors for Lymph Node Metastasis in Solitary Papillary Thyroid Carcinomas: A Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid gland; Thyroid neoplasms; Carcinoma; Papillary; Lymphatic metastasis
ID Thyroid gland; Thyroid neoplasms; Carcinoma; Papillary; Lymphatic metastasis
AB Identifying risk factors for neck lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is important for patient prognosis establishment.We conducted a retrospective study among 317 patients with solitary PTC. Factors associated with clinically evident LNM were evaluated. LNM were identified in 69 (21.7%) patients. Central compartment (17.3%) and lateral compartment (9.4 %) were involved. Thyroid capsule invasion and extrathyroidal extension were found to be independent risk factors for both central and lateral compartment metastasis in multivariate analysis. Larger diameter was associated with central compartment metastasis in logistic regression model, whereas male gender only with lateral compartment metastasis. As closer tumors were positioned in relation to glandular capsule we expected rising rates of nodal spread. It was unlikely to find clinically evident neck LNM among patients with centrally located tumors.
C1 [Girardi, Muradas Fabio] Santa Casa Hospital Complex, Santa Rita Hospital, Department of Head and Neck SurgeryPorto Alegre, RS, Brazil.
[Barra, Bizarro Marinez] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, RS, Brazil.
[Zettler, Galleano Claudio] Santa Casa Hospital Complex, Santa Rita Hospital, Department of PathologyPorto Alegre, RS, Brazil.
RP Girardi, MF (reprint author), Santa Casa Hospital Complex, Santa Rita Hospital, Department of Head and Neck Surgery, Porto Alegre, Brazil.
EM fabiomgirardi@gmail.com
CR Sherman SI, 2003, Thyroid carcinoma. Lancet 361(9356):501–11
Davies L,Welch HG, 2006, Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295(18):2164–7
Baek SK, Jung KY, Kang SM, Kwon SY, Woo JS, Cho SH et al, 2010, Clinical risk factors associated with cervical lymph node recurrence in papillary thyroid carcinoma. Thyroid 20(2):147–52
Beasley NJ, Lee J, Eski S, Walfsh P, Witterick I, 2002, Impact of nodal metastases on prognosis in patients with well-differentiated thyroid cancer. Arch Otolaryngol Head Neck Surg 128(7):825–8
So YK, Son YI, Hong SD, SeoMY, Baek CH, Jeong HS et al, 2010, Subclinical lymph node metastasis in papillary thyroid microcarcinoma: a study of 551 resections. Surgery 148(3):526–31
Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fugimoto Y, 2010, Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: Our treatment strategies and outcomes. World J Surg 34(6):1222–31
Roti E, degli Uberti EC, Bondanelli M, Braverman LE, 2008, Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 159(6):659–73
Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K et al, 2004, Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg 28(11):1115–21
Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K et al, 2004, Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid. World J Surg 28(5):498–501
Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T et al, 2003, Lymph node metastasis from 259 papillary thyroid Microcarcinomas: Frequency, Pattern of Occurrence and Recurrence, andOptimal Strategy forNeckDissection. Ann Surg 237(3):399–407
Hughes CJ, Shaha AR, Shah JP, Loree TR, 1996, Impact of lymph nodemetastasis in differentiated carcinoma of the thyroid: amatchedpair analysis. Head Neck 18(2):127–32
Sarvanan K, Bapuraj JR, Sharma SC, Radotra BD, Khandelwal N, Suri S, 2002, Computed tomography and ultrasonographic evaluation ofmetastatic cervical lymph nodes with surgicoclinicopathologic correlation. J Laryngol Otol 116(3):194–9
Lee DW, Ji YB, Sung ES, Park JS, Lee YJ, Park DW et al, 2013, Roles of ultrasonography and computed tomography in the surgical management of cervical lymph node metastases in papillary thyroid carcinoma. Eur J Surg Oncol 39(2):191–6
Jeong HS, Baek CH, Son YI, Choi JY, Kim HJ, Ko YH et al, 2006, Integrated 18 F-FDG PET/CT for the initial evaluation of cervical node level of patients with papillary thyroid carcinoma: comparison with ultrasound and contrast-enhanced CT. Clin Endocrinol, Oxf, 65(3):402–7
Henry JF, Gramatica L, Denizot A, Kvachenyuk A, Puccini M, Defechereux T, 1998, Morbidity of prophylactic lymph node dissection in the central neck area in patients with papillary thyroid carcinoma. Langenbecks Arch Surg 383(2):167–9
Pereira JA, Jimeno J,Miquel J, IglesiasM,Munne A, Sancho JJ et al, 2005, Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 138(6):1095–100
Edge SE, Byrd DR, Carducci MA, Compton CA, 2010, AJCC cancer staging manual. Springer, New York
Shah JP, 1990, Cervical lymph node metastases—diagnostic, therapeutic, and prognostic implications.Oncology, Williston Park, 4(10): 61–9
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Cho JK, Kim JY, Jeong CY, Jung EJ, Park ST, Jeong SH et al, 2012, Clinical features and prognostic factors in papillary thyroid microcarcinoma depends on age. J Korean Surg Soc 82(5):281–7
Choi SJ, Kim TY, Lee JC, Shong YK, Cho KJ, Ryu JS et al, 2008, Is routine central neck dissection necessary for the treatment of papillary thyroid microcarcinoma? Clin Exp Otorhinolayngol 1(1):41–5
Zuniga S, Sanabria A, 2009, Prophylactic central neck dissection in stage N0 papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 135(11):1087–91
Nam IC, Park JO, Joo YH, Cho KJ, Kim MS, 2013, Pattern and predictive factors of regional lymph node metastasis in papillary thyroid carcinoma: A prospective study. Head Neck 35(1):40–45
Jeong JJ, Lee YS, Lee SC, Kang SW, Chung WY, Chang HS et al, 2011, A scoring system for prediction of lateral neck node metastasis from papillary thyroid cancer. J Korean Med Sci 26(8): 996–1000
Gulben K, Berberoglu U, Celen O, Mersin HH, 2008, Incidental papillary microcarcinoma of the thyroid - factors affecting lymph node metastasis. Langenbecks Arch Surg 393(1):25–9
Choi Y, Park KJ, Ryu S, Kim DH, Yun J, Kang DK et al, 2012, Papillary thyroid carcinoma involving cervical neck lymph nodes: correlations with lymphangiogenesis and ultrasound features. Endocr J 59(10):941–8
Hunt JP, Buchmann LO, Wang L, Abraham D, 2011, An analysis of factors predicting lateral cervical nodal metastases in papillary carcinoma of the thyroid. Arch Otolaryngol Head Neck Surg 137(11): 1141–5
Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y et al, 2012, Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab 97(4):1250–7
Mirallie E, Sagan C, Hamy A, Paineau J, Kahn X, Le Neel JC et al, 1999, Predictive factors for node involvement in papillary thyroid carcinoma. Univariate and multivariate analyses. Eur J Cancer 35(3): 420–3
Ortiz S, Rodriguez JM, Soria T, Perez-Flores D, Pinero A, Moreno J et al, 2001, Extrathyroid spread in papillary carcinoma of the thyroid: clinicopathological and prognostic study. Otolaryngol Head Neck Surg 124(3):261–5
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Kim SS, Lee BJ, Lee JC, Kim SJ, Lee SH, Jeon YK et al, 2011, Preoperative ultrasonographic tumor characteristics as a predictive factor of tumor stage in papillary thyroid carcinoma. Head Neck 33(12):1719–26
Foschini MP, Papotti M, Parmeggiani A, Tallini G, Castaldini L, Meringolo D et al, 2004, Three-dimensional reconstruction of vessel distribution in benign and malignant lesions of thyroid. Virchows Arch 445(2):189–98
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Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K et al, 2006, Minimal extrathyroid extension does Not affect the relapsefree survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the Age of 45 years. Surg Today 36(1):12–8
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 59
EP 64
DI 10.1007/s12253-014-9788-4
PG 6
ER
PT J
AU Alsaegh, AM
Miyashita, H
Zhu, RSh
AF Alsaegh, Amjed Mohammed
Miyashita, Hitoshi
Zhu, Rong Sheng
TI Expression of Human Papillomavirus is Correlated with Ki-67 and COX-2 Expressions in Keratocystic Odontogenic Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus (HPV); Keratocyst; Odontogenic; Ki-67; Cyclooxygenase-2 (COX-2)
ID Human papillomavirus (HPV); Keratocyst; Odontogenic; Ki-67; Cyclooxygenase-2 (COX-2)
AB The aim of the current study was to investigate the presence of human papillomavirus (HPV) and evaluate its association with Ki-67 and cyclooxygenase-2 (COX-2) expressions in keratocystic odontogenic tumor (KCOT).Nineteen cases were included in the present study. Conventional PCR method and immunohistochemical analysis were performed for the detection of HPV-DNA and HPV-L1 capsid protein. Moreover, the expressions of Ki-67 and COX-2 proteins were analyzed immunohistochemically. HPV-DNA was detected in 36.8 % (7/19) of tumor samples, whilst HPV-L1 protein was identified in 68.4 % (13/19) of them. The Kappa coefficient statistical test showed a moderate agreement (κ0.424) between PCR and IHC assays for HPV detection. Expression of HPV-DNA was positively correlated with Ki-67 and COX-2 expressions (p<0.05), whereas HPV-L1 positive staining was positively correlated with COX-2 (p<0.05) and highly associated with those of Ki-67 (p< 0.01). There was no significant correlation between the presence of HPV and the recurrence of the studied lesions. The results of the current study showed that active HPV infection was present in the odontogenic epithelium of KCOT, and it was associated with increased proliferation rate and COX-2 expression. These findings suggest that HPV may have a role in the pathogenesis and aggressiveness of KCOT. Based on these conclusions, we recommend further investigations of HPV vaccine or antiviral therapy and COX-2 inhibitors as nonsurgical options in the prevention and management of KCOT.
C1 [Alsaegh, Amjed Mohammed] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Stomatology, 430030 Wuhan, China.
[Miyashita, Hitoshi] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Stomatology, 430030 Wuhan, China.
[Zhu, Rong Sheng] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Stomatology, 430030 Wuhan, China.
RP Zhu, RSh (reprint author), Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Stomatology, 430030 Wuhan, China.
EM tongji36@yahoo.com
CR Barnes L, Eveson JW, Reichart P, Sidransky D, 2005, World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. IARC, Lyon
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Gadbail AR, Chaudhary M, Patil S, Gawande M, 2009, Actual Proliferating Index and p53 protein expression as prognostic marker in odontogenic cysts. Oral Dis 15:490–498
de Oliveira MG, Lauxen Ida S, Chaves AC, Rados PV, Sant'Ana Filho M, 2011, Odontogenic epithelium: immunolabeling of Ki-67, EGFR and survivin in pericoronal follicles, dentigerous cysts and keratocystic odontogenic tumors. Head Neck Pathol 5:1–7
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Gonzalez-Moles MA, Mosqueda-Taylor A, Delgado-Rodriguez M et al, 2006, Analysis of p53 protein by PAb240, Ki-67 expression and human papillomavirus DNA detection in different types of odontogenic keratocyst. Anticancer Res 26:175–181
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 65
EP 71
DI 10.1007/s12253-014-9789-3
PG 7
ER
PT J
AU Gurgel, CD
Valenca-Junior, TJ
Dornelas, AC
Vieira, BR
Maia-Filho, TAJ
Lima-Junior, CPR
Ribeiro, AR
Almeida, RCP
AF Gurgel, Cordeiro Daniel
Valenca-Junior, Telmo Jose
Dornelas, Aparecida Conceicao
Vieira, Braga Renato
Maia-Filho, Tarcisio Alves Joao
Lima-Junior, Cesar Pereira Roberto
Ribeiro, Albuquerque Ronaldo
Almeida, Roberto Carvalho Paulo
TI Immunoexpression of Metalloproteinases 2 and 14 and TIMP-2 Inhibitor in Main Types of Primary Gastric Carcinomas and Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Immunohistochemistry; Macrophage; Metalloproteinase; Metastasis
ID Gastric cancer; Immunohistochemistry; Macrophage; Metalloproteinase; Metastasis
AB Metalloproteinase-2 (MMP-2) and −14 (MMP-14) and the tissue inhibitor of metalloproteinases type 2 (TIMP-2) participate in epithelial-mesenchymal transition and tumor progression in many cancers. However, the correlation between these enzymes in gastric cancer and the metastatic potential to their respective lymph node needs to be determined. Here, we evaluated the expression of these enzymes in gastric carcinoma and lymph node metastases and their possible involvement in tumor progression. Histological samples from 83 patients with gastric cancer and their respective lymph nodes were used. MMP-2,MMP-14 and TIMP-2 immunoexpression was scored. TIMP-2 expression in tumor-associated macrophages occurred more frequently than in normal mucosa (P=0.0128). Female tumor samples presented higher MMP-2 expression (P= 0.0248), while TIMP-2 occurred mainly in patients over 50 years old (P=0.0034). MMP-2 was higher expressed in primary tumor macrophages than in neoplastic cells (P=0.0118), and was also seen in macrophages from metastatic-affected lymph nodes of intestinal and diffuse histotypes (P=0.0006). MMP-2, MMP-14 and TIMP-2 expression in mononuclear cells might be correlated with progression of gastric cancer. MMP-14 production by macrophages appears to be more involved in diffuse gastric cancer progression.
C1 [Gurgel, Cordeiro Daniel] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
[Valenca-Junior, Telmo Jose] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
[Dornelas, Aparecida Conceicao] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
[Vieira, Braga Renato] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
[Maia-Filho, Tarcisio Alves Joao] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
[Lima-Junior, Cesar Pereira Roberto] Federal University of Ceara, Faculty of Medicine, Department of Physiology and PharmacologyFortaleza, Ceara, Brazil.
[Ribeiro, Albuquerque Ronaldo] Federal University of Ceara, Faculty of Medicine, Department of Physiology and PharmacologyFortaleza, Ceara, Brazil.
[Almeida, Roberto Carvalho Paulo] Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, Rua Monsenhor Furtado S/N, Rodolfo Teofilo, 60430-350 Fortaleza, Ceara, Brazil.
RP Almeida, RCP (reprint author), Federal University of Ceara, Faculty of Medicine, Department of Pathology and Forensic Medicine, 60430-350 Fortaleza, Brazil.
EM paulorcalmeida@uol.com.br;paulo.almeida@ufc.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 73
EP 81
DI 10.1007/s12253-014-9790-x
PG 9
ER
PT J
AU Zhong, W
Yu, Z
Zhan, J
Yu, T
Lin, Y
Xia, ZSh
Yuan, YH
Chen, QK
AF Zhong, Wa
Yu, Zhong
Zhan, Jun
Yu, Tao
Lin, Ying
Xia, Zhong-Sheng
Yuan, Yu-Hong
Chen, Qi-Kui
TI Association of Serum Levels of CEA, CA199, CA125, CYFRA21-1 and CA72-4 and Disease Characteristics in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Cancer marker; TNM stage; Duke stage; Overall survival
ID Colorectal cancer; Cancer marker; TNM stage; Duke stage; Overall survival
AB Identifying predictive biomarkers for colorectal cancer would facilitate diagnosis and treatment of the disease. This study aimed to investigate the association of the serological biomarkers CEA, CA19–9, CA125, CYFRA21–1 and CA72–4 with patient characteristics and disease outcomes in colorectal cancer. Patients (N=373) with colorectal cancer were evaluated for the association of CEA, CA19–9, CA125, CYFRA21–1, and CA72–4 pre and post-surgery and at disease recurrence with demographics, disease characteristics including pathological types, degree of differentiation, invasion depth, abdominal lymph node metastasis, TMN stage, Dukes stage, location of cancer and metastasis, and disease outcomes. It was more common for a patient to express these markers prior to surgery and at disease recurrence than following surgery. Overall, the serum levels of CEA, CA19–9, CA125, CYFRA21–1, and CA72–4 were not associatedwith age, gender, pathological type and location of cancer (all P-values >0.05), but were associated with the poor tumor differentiation, higher tumor invasion, greater degree of abdominal lymph node metastasis, and higher TNM and Duke stage tumors (all P-values<0.01). CEA expressionwas associatedwith older ages (median age 65 years). Multivariate analysis indicated that CEA was correlated with overall survival and none of the markers correlated with disease recurrence. The expression of CEA, CA19–9, CA125, CYFRA21–1, and CA72–4 was associated with specific disease characteristics which tended to indicated more advanced disease and disease recurrence consistent with these biomarkers being useful for detecting colorectal cancer.
C1 [Zhong, Wa] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Yu, Zhong] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Zhan, Jun] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Yu, Tao] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Lin, Ying] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Xia, Zhong-Sheng] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Yuan, Yu-Hong] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
[Chen, Qi-Kui] Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, No.107 Yanjiang Xi Road, Yuexiu District, 510120 Guangzhou, Guangdong, China.
RP Chen, QK (reprint author), Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Gastroenterology, 510120 Guangzhou, China.
EM qikuichen@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 83
EP 95
DI 10.1007/s12253-014-9791-9
PG 13
ER
PT J
AU Moatter, T
Aban, M
Iqbal, W
Pervez, Sh
AF Moatter, Tariq
Aban, Muniba
Iqbal, Waseem
Pervez, Shahid
TI Cyclooxygenase-2 Polymorphisms and Breast Cancer Associated Risk in Pakistani Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cyclooxygenase; Cox-2; Breast Cancer; Polymorphism; Haplotypes; RFLP
ID Cyclooxygenase; Cox-2; Breast Cancer; Polymorphism; Haplotypes; RFLP
AB Prostaglandins produced by Cyclooxygenase-2 enzyme have been implicated to have a role in breast carcinogenesis. Several single nucleotide polymorphisms (SNPs) linked to COX-2 enzyme are reported to modulate its expression. The aim of the present study was to examine association of these SNPs to breast cancer risk in Pakistani patients. Methods In this case–control study, three sequence variants rs689465, rs689466, rs20417 in the promoter region of COX- 2 were screened to evaluate the association with breast cancer risk. A total of 150 breast cancer patients and 101 healthy control genomic DNA were genotyped for rs689456, rs689466, rs20417 and their genotypes distribution in cases and control were compared using Pearson chi square test. Risk association was analyzed through odd ratio calculated by logistic regression. Results A screening analysis of COX-2 SNPs in 101 healthy controls showed distribution of Minor allelic frequency distribution of SNPs as follows : rs689465 (0.12), rs689466 (0.15), rs20417 (0.23). Further analyses revealed that their observed genotype frequencies were consistent with Hardy Weinberg equilibrium and strong linkage disequilibrium was identified between rs20417, rs689465 and rs689466. The Combined allele variants analysis showed that Haplotype rs68965G- 689466A-20417C (OR 2.909; CI 95 %1.3776.327; P=0.007) was significantly associated with breast cancer. Conclusions Our results indicate no strong association between three most frequent COX-2 SNPs rs689465 rs689466, rs20417 studied with breast cancer risk in the single locus analysis. However, our data suggested that combined COX-2 SNP haplotype have a role in breast cancer associated risk in Pakistani patients.
C1 [Moatter, Tariq] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
[Aban, Muniba] Baqai Medical University, Department of PathologyKarachi, Pakistan.
[Iqbal, Waseem] Baqai Medical University, Department of PathologyKarachi, Pakistan.
[Pervez, Shahid] The Aga Khan University, Department of Pathology and Microbiology, Stadium Road, 74800 Karachi, Pakistan.
RP Pervez, Sh (reprint author), The Aga Khan University, Department of Pathology and Microbiology, 74800 Karachi, Pakistan.
EM shahid.pervez@aku.edu
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Brasky TM, Bonner MR, Moysich KB, Ambrosone CB, Nie J, Tao MH et al, 2011, Genetic variant in Cox-2, Non-steroidal antiinflammatory drug and breast cancer risk in the Western New York Exposures and Breast Cancer, WEB, Study. Breast Cancer Res Treat 126:157–165
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 97
EP 101
DI 10.1007/s12253-014-9792-8
PG 5
ER
PT J
AU Pereira, LD
dos Santos Ferreira, CA
Faria, PdG
Kwee, KJ
AF Pereira, Lima Debora
dos Santos Ferreira, Carolina Ana
Faria, Pinto de Giselle
Kwee, Kiemlian Jolie
TI Autophagy Interplays with Apoptosis and Cell Cycle Regulation in the Growth Inhibiting Effect of Trisenox in HEP-2, a Laryngeal Squamous Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laryngeal squamous cancer; Trisenox; L-buthionine sulfoximine; Autophagy; Apoptosis
ID Laryngeal squamous cancer; Trisenox; L-buthionine sulfoximine; Autophagy; Apoptosis
AB Laryngeal squamous cell carcinoma (LSCC) is the most common among several types of head and neck cancers. Current treatments have a poor effect on early and advanced cases, and further investigations for novel agents against LSCCs are desirable. In this study, we elucidate the cytotoxic enhancing effect of arsenic trioxide (As2O3) combined with L-buthionine sulfoximine (BSO) in LSCC. The effect of BSO with As2O3 or Cisplatin (CDDP) on cell viability was examined using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The reactive oxygen species (ROS) levels, cell cycle, and apoptosis were measured by flow cytometry using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), propidium iodide (PI) and annexin V/PI. The acidic vacuolar organelles were visualized by fluorescence microscope and quantified using flow cytometry. Neither CDDP nor As2O3 when used alone reduced the cell viability. BSO was found to enhance only As2O3 sensitivity, leading to G2/M arrest and autophagy with no correlation of ROS induction. This result suggests that modulation of glutathione enhances autophagy, which interplays with apoptosis. In this study, we obtained initial preclinical evidence for the potential efficacy of these drugs in a combined therapy protocol.
C1 [Pereira, Lima Debora] A. C. Camargo Cancer Hospital, Department of StomatologySao Paulo, Brazil.
[dos Santos Ferreira, Carolina Ana] Instituto Nacional de Cancer Jose Alencar Gomes da Silva (INCA), Programa de Pos-Graduacao em Oncologia do Instituto Nacional de Cancer (PPGO-INCA)Rio de Janeiro, Brazil.
[Faria, Pinto de Giselle] Universidade Federal da Bahia (UFBA), Instituto de Ciencias da Saude (ICS), Departamento de BiorregulacaoBahia, Brazil.
[Kwee, Kiemlian Jolie] INCA, Coordenacao de PesquisaRio de Janeiro, Brazil.
RP Kwee, KJ (reprint author), INCA, Coordenacao de Pesquisa, Rio de Janeiro, Brazil.
EM jkwee@inca.gov.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 103
EP 111
DI 10.1007/s12253-014-9794-6
PG 9
ER
PT J
AU Basaran, D
Salman, CM
Boyraz, G
Selcuk, I
Usubutun, A
Ozgul, N
Yuce, K
AF Basaran, Derman
Salman, Coskun Mehmet
Boyraz, Gokhan
Selcuk, Ilker
Usubutun, Alp
Ozgul, Nejat
Yuce, Kunter
TI Accuracy of Intraoperative Frozen Section in the Evaluation of Patients with Adnexal Mass: Retrospective Analysis of 748 Cases with Multivariate Regression Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Frozen section; Ovarian tumor; Adnexalmass; Ovarian cancer; Borderline ovarian tumor
ID Frozen section; Ovarian tumor; Adnexalmass; Ovarian cancer; Borderline ovarian tumor
AB Objective: To evaluate the accuracy of intraoperative frozen section in the evaluation of patients with adnexal mass and to define the clinicopathological factors associated with misdiagnosis during frozen section evaluation. Methods: The clinicopathological data of patients who underwent exploratory laparotomy for adnexal mass were reviewed. Results of the intraoperative frozen section and permanent histology reports were compared. Univariate and multivariate analyses were performed to reveal factors associated with misdiagnosis. Results: The study group consisted of 748 patients. Of these patients, 509 (68.0 %) had benign, 43 (5.7 %) had borderline, 196 (26.2 %) had malignant histological diagnosis at permanent section. The overall agreement between intraoperative frozen section and permanent pathology was 96.8 %. Twenty four out of 745 cases (3.8 %) were misdiagnosed by frozen section. Univariate analysis showed that borderline histology (p<0.0001) and tumor size larger than 10 cm (p=0.012) were associated with misdiagnosis. According to multivariate analysis, borderline histology (OR: 22.6, p<0.0001) was the only independent predictor for misdiagnosis during frozen examination. Conclusion: The frozen section evaluation of the adnexal mass is highly accurate. However, tumor size greater than 10 cm and borderline histology are the factors that adversely influence the accuracy of intraoperative frozen section. Clinicians must be aware of these pitfalls during intraoperative decision making following frozen section report.
C1 [Basaran, Derman] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
[Salman, Coskun Mehmet] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
[Boyraz, Gokhan] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
[Selcuk, Ilker] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
[Usubutun, Alp] Hacettepe University, Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Ozgul, Nejat] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
[Yuce, Kunter] Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sihhiye, 06100 Ankara, Turkey.
RP Salman, CM (reprint author), Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology, 06100 Ankara, Turkey.
EM csalman@hacettepe.edu.tr
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Medeiros LR, Rosa DD, Edelweiss MI, Stein AT, Bozzetti MC, Zelmanowicz A et al, 2005, Accuracy of frozen-section analysis in the diagnosis of ovarian tumors: a systematic quantitative review. Int J Gynecol Cancer 15(2):192–202
Geomini PM, Zuurendonk LD, Bremer GL, de Graaff J, Kruitwagen RF, Mol BW, 2005, The impact of size of the adnexal mass on the accuracy of frozen section diagnosis. Gynecol Oncol 99(2):362–366
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WangKG, Chen TC,Wang TY, Yang YC, Su TH, 1998, Accuracy of frozen section diagnosis in gynecology. Gynecol Oncol 70(1):105– 110
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 113
EP 118
DI 10.1007/s12253-014-9795-5
PG 6
ER
PT J
AU Acikalin, A
Gumurdulu, D
Bagir, KE
Torun, G
Guzel, BA
Zeren, H
Vardar, AM
AF Acikalin, Arbil
Gumurdulu, Derya
Bagir, Kilic Emine
Torun, Goncagul
Guzel, Baris Ahmet
Zeren, Handan
Vardar, Ali Mehmet
TI The Guidance of Intraoperative Frozen Section For Staging Surgery in Endometrial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Intraoperative frozen section; Staging surgery
ID Endometrial cancer; Intraoperative frozen section; Staging surgery
AB The objective of this study was to evaluate the reliability of an intraoperative frozen section during the endometrial carcinoma staging surgery procedure. The paraffin section reports of 291 cases with endometrial carcinoma were compared with intraoperative frozen section reports, which were diagnosed in the Pathology Department of Cukurova University, Medical Faculty between June 2006 and December 2012. The reports were reviewed for diagnostic accuracy of the frozen section in terms of histological subtype, grade, and myometrial invasion. Concordance values between frozen and paraffin section reports were 86, 84.3, and 91.6 % for histological subtype, grade, and myometrial invasion, respectively. When collectively evaluated, two (0.7 %) of 291 patients were inappropriately operated on due to frozen section reports. Intraoperative frozen section is a reliable guide for surgeons to evaluate the risk group of patients with endometrial cancer and prevent an unnecessary staging surgery operation.
C1 [Acikalin, Arbil] Cukurova University, School of Medicine, Pathology Department, Saricam, 01330 Adana, Turkey.
[Gumurdulu, Derya] Cukurova University, School of Medicine, Pathology Department, Saricam, 01330 Adana, Turkey.
[Bagir, Kilic Emine] Cukurova University, School of Medicine, Pathology Department, Saricam, 01330 Adana, Turkey.
[Torun, Goncagul] Cukurova University, School of Medicine, Pathology Department, Saricam, 01330 Adana, Turkey.
[Guzel, Baris Ahmet] Cukurova University, School of Medicine, Obstetrics and Gynecology DepartmentAdana, Turkey.
[Zeren, Handan] Acibadem University, School of Medicine, Pathology DepartmentIstanbul, Turkey.
[Vardar, Ali Mehmet] Cukurova University, School of Medicine, Obstetrics and Gynecology DepartmentAdana, Turkey.
RP Acikalin, A (reprint author), Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
EM arbilavci@yahoo.com
CR Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB, 1987, Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group study. Cancer 60(8 Suppl): 2035–2041
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ArkoD, Takac I, 2000, High frequency transvaginal ultrasonography in preoperative assessment of myometrial invasion in endometrial cancer. J Ultras Med 19(9):639–643
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Kumar S, Medeiros F, Dowdy SC, Keeney GL, Bakkum-Gamez JN, Podratz KC, ClibyWA, Mariani A, 2012, A prospective assessment of the reliability of frozen section to direct intraoperative decision making in endometrial cancer. Gynecol Oncol 127(3):525–531., DOI 10.1016/j.ygyno.2012.08.024
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Sanjuan A, Cobo T, Pahisa J, Escaramis G, Ordi J, Ayuso JR, Garcia S, Hernandez S, Torne A, Roman SM, Lejarcegui JA, Vanrell JA, 2006, Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer: role of magnetic resonance imaging and frozen section. Int J Gynecol Cancer 16(1):385–390., DOI 10.1111/J.1525- 1438.2006.00414.X
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Maneschi F, Nardi S, Sarno M, Manicone AM, Perugini A, Partenzi A, Lambiase A, Pericoli N, Maiorca A, Travaini S, 2007, Endometrial carcinoma. Intraoperative evaluation of myometrial invasion. A prospective study. Int J Gynecol Cancer 17(4):940
Obrzut B, Obrzut M, Skret-Magierlo J, Skret A, Ulman D, Krol P, Zmuda M, 2008, Value of the intraoperative assessment of the depth ofmyometrial invasion in endometrial carcinoma. Ginekol Pol 79(6): 404–409
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 119
EP 122
DI 10.1007/s12253-014-9796-4
PG 4
ER
PT J
AU Jenner, S
Wiedorn, HK
Techel, D
AF Jenner, Stefan
Wiedorn, Herrmann Klaus
Techel, Dieter
TI Development of a DUSP9 Methylation Screening Assay
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DUSP9; Colorectal cancer; Promoter methylation; CIMP; Pyrosequencing
ID DUSP9; Colorectal cancer; Promoter methylation; CIMP; Pyrosequencing
AB A methylation screening assay for DUSP9 (dualspecificity phosphatase 9) has been developed and applied on 79 FFPE samples from patients with colorectal cancer (CRC) and 22 corresponding tumor free colon samples in this study. Quantitative pyrosequencing was used for the determination of the methylation in the promoter CpG island, including 83 CpG motifs. In this way, the methylation pattern of the 11 tumor samples with the weakest and the strongest methylation could be identified and were compared to their corresponding tumor free colon samples. Forty six percent of the weakly methylated samples showed no significant difference to their tumor free counterparts, whereas in 27 % of the cases an increased or reduced methylation was detectable. For the strongly methylated tumor samples only 18 % showed no significant difference to their tumor free counterparts, whereas 82 % were significantly stronger methylated. In CRC, the aberrant promoter methylation of tumor suppressor genes is one aspect that defines the CpG island methylator phenoptype (CIMP) and is frequently observed in a subpopulation of cases. Patients harboring a CIMP phenotype often show additional clinicopathological characteristics, the so called CIMP features. Interestingly, no CIMP features were found for the weakly methylated samples analyzed in this study but could be seen in 82 % of the strongly methylated cases, indicating a possible use for DUSP9 as CIMP marker.
C1 [Jenner, Stefan] Katharinen Hospital Stuttgart, Department of Pathology, Division of Molecular Pathology, Kriegsbergstr. 60, 70174 Stuttgart, Germany.
[Wiedorn, Herrmann Klaus] Katharinen Hospital Stuttgart, Department of Pathology, Division of Molecular Pathology, Kriegsbergstr. 60, 70174 Stuttgart, Germany.
[Techel, Dieter] Katharinen Hospital Stuttgart, Department of Pathology, Division of Molecular Pathology, Kriegsbergstr. 60, 70174 Stuttgart, Germany.
RP Jenner, S (reprint author), Katharinen Hospital Stuttgart, Department of Pathology, Division of Molecular Pathology, 70174 Stuttgart, Germany.
EM S.Jenner@Klinikum-Stuttgart.de
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Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE, 2010, Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 16(3):790–799
Dunn J, Baborie A, Alam F, Joyce K, Moxham M, Sibson R et al, 2009, Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer 101(1):124–131
Kondoh K, Nishida E, 2007, Regulation of MAP kinases by MAP kinase phosphatases. Biochim Biophys Acta 1773(8):1227–1237
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 123
EP 130
DI 10.1007/s12253-014-9797-3
PG 8
ER
PT J
AU Zhou, L
Rui, JA
Wang, ShB
Chen, ShG
Qu, Q
AF Zhou, Li
Rui, Jing-An
Wang, Shao-Bin
Chen, Shu-Guang
Qu, Qiang
TI Clinicopathological Predictors of Poor Survival and Recurrence After Curative Resection in Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Portal vein tumor thrombosis; Survival; Recurrence
ID Hepatocellular carcinoma; Portal vein tumor thrombosis; Survival; Recurrence
AB Many factors associated with long-term outcome in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) were previously identified. However, those in HCC without PVTT have not been elucidated. This study was designed to define the risk factors of poor postsurgical survival and recurrence in this subgroup of HCC. Medical records and follow-up data of consecutive 152 patients with PVTT-absent HCC underwent curative resection were reviewed. The impacts of clinical and pathological variables on patient survival and recurrence were evaluated by univariate and multivariate analyses. It was shown that Edmondson-Steiner grade, TNM stage, microvascular invasion (MVI), satellite nodule, serum AFP level, tumor size and number were significant for tumor-specific and/or tumor-free survival in univariate analysis. Among them, Edmondson- Steiner grade and TNM stage were of independent significances for both, whereas satellite nodule independently predicted tumor-free survival. In Chi-square test, Edmondson- Steiner grade, TNM stage and MVI were significantly related to overall as well as early recurrence. Stepwise logistic regression identified Edmondson-Steiner grade as the single independent predictor of both. To be summarized, variables that are associated with poor prognosis and recurrence in HCC without PVTT are all tumor-related ones. Of these, differentiation degree might be of particular importance.
C1 [Zhou, Li] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Rui, Jing-An] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Wang, Shao-Bin] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Chen, Shu-Guang] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Qu, Qiang] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
RP Zhou, L (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
EM lizhou02@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 131
EP 138
DI 10.1007/s12253-014-9798-2
PG 8
ER
PT J
AU Cui, G
Yang, H
Zhao, J
Yuan, A
Florholmen, J
AF Cui, Guanglin
Yang, Hang
Zhao, Jianbo
Yuan, Aping
Florholmen, Jon
TI Elevated Proinflammatory Cytokine IL-17A in the Adjacent Tissues Along the Adenoma-Carcinoma Sequence
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IL-17A; Adjacent mucosa; Colorectum; Cancer
ID IL-17A; Adjacent mucosa; Colorectum; Cancer
AB Considerable evidence has suggested that chronic inflammation is a causative factor in the development of human colorectal cancer (CRC). Interleukin (IL)-17A produced mainly by Th17 cells is a novel proinflammatory cytokine and increased IL-17A is associated with colorectal neoplastic transformation. In this study, we have evaluated the expression of IL-17A in the adjacent tissues along the colorectal adenoma-carcinoma sequence. The expression of IL- 17A in the adjacent tissues of colorectal adenoma (adenomaadjacent, n=32) and sporadic CRC (CRC-adjacent, n=45) was examined. In addition, the expression pattern of Th17 cell differentiation stimulators (IL-1β, IL-6 and IL-23A) in the adjacent tissues were also examined. The results showed that the expression level of IL-17A mRNA was non-statistically increased (4-fold higher) in the adenoma-adjacent tissues and it became significantly increased (9-fold higher) in the CRC-adjacent tissues as compared with the control. The expression level of IL-17A in the CRC-adjacent tissues was not associated with CRC clinicopathological parameters and overall survival. Immunohistochemistry confirmed an increased density of intraepithelial IL-17A expressing cells in the CRC-adjacent tissues. The Th17 cell differentiation simulators IL- 1β and IL-6 were also shown in an increase trend from the adenoma-adjacent to CRC-adjacent tissues. These results provide evidence that IL-17A/Th17 response is enhanced in the adjacent tissues during the colorectal neoplastic transformation.
C1 [Cui, Guanglin] The Second Affiliated Hospital of Zhengzhou University, Department of GastroenterologyZhengzhou, Henan, China.
[Yang, Hang] The Second Affiliated Hospital of Zhengzhou University, Department of GastroenterologyZhengzhou, Henan, China.
[Zhao, Jianbo] The Second Affiliated Hospital of Zhengzhou University, Department of GastroenterologyZhengzhou, Henan, China.
[Yuan, Aping] The Second Affiliated Hospital of Zhengzhou University, Department of GastroenterologyZhengzhou, Henan, China.
[Florholmen, Jon] University of Tromso, Faculty of Medicine, Institute of Clinical Medicine, Laboratory of Gastroenterology & NutritionTromso, Norway.
RP Cui, G (reprint author), The Second Affiliated Hospital of Zhengzhou University, Department of Gastroenterology, Zhengzhou, China.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 139
EP 146
DI 10.1007/s12253-014-9799-1
PG 8
ER
PT J
AU Voros, A
Csorgo, E
Kovari, B
Lazar, P
Kelemen, Gy
Rusz, O
Nyari, T
Cserni, G
AF Voros, Andras
Csorgo, Erika
Kovari, Bence
Lazar, Peter
Kelemen, Gyongyi
Rusz, Orsolya
Nyari, Tibor
Cserni, Gabor
TI Different Methods of Pretreatment Ki-67 Labeling Index Evaluation in Core Biopsies of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Their Relation to Response to Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast carcinoma; Evaluation methods; Ki-67; Neoadjuvant therapy; Tumor regression
ID Breast carcinoma; Evaluation methods; Ki-67; Neoadjuvant therapy; Tumor regression
AB Increased proliferation activity of breast cancer cells evaluated by Ki-67 immunohistochemistry, i.e. a high Ki-67 labeling index (Ki-67 LI), may predict better tumor regression in case of neoadjuvant chemotherapy. Despite recommendations for the evaluation of Ki-67 LI, there are variations in methodology. We assessed the effect of different evaluation methods on the Ki-67 LI in patients with different response to neoadjuvant chemotherapy. Thirty pretreatment core-biopsy samples of patients receiving neoadjuvant docetaxel-epirubicin chemotherapy with or without capecitabine were evaluated for their Ki-67 LI. Pathologic regression was categorized as no regression, partial regression and complete regression, with 10 cases in each category. Three antibodies (MIB1, B56, SP6), 4 observers and 4 methods (counting or estimating on glass slides and counting or estimating on representative digital images) were compared. The Kruskal-Wallis test and analyses of variance were performed to investigate the differences in Ki-67 LIs between different clinical outcomes (tumor regression categories). Breast carcinomas with pathological complete regression had a higher mean Ki-67 LI than tumors not achieving complete regression with any methods, observers and antibodies investigated, although there was a variation between different evaluations in what may represent high proliferation. Estimating the Ki-67 LI on digital images representing the highest proliferation in the core biopsy seemed the best in separating complete responders from non-responders. High Ki-67 LI values were more likely associated with pathological complete regression independently of the method of evaluation used, although the definition of high proliferation is problematic. Estimating the Ki-67 LI may be an adequate method of evaluation.
C1 [Voros, Andras] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Csorgo, Erika] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Kovari, Bence] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Lazar, Peter] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Rusz, Orsolya] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Nyari, Tibor] University of Szeged, Department of Medical Informatics, Koranyi fasor 9, 6720 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u 2, 6725 Szeged, Hungary.
RP Voros, A (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM andrasvoros@libero.it
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 147
EP 155
DI 10.1007/s12253-014-9800-z
PG 9
ER
PT J
AU Omran, MO
Al Sheeha, M
AF Omran, Mahmoud Ola
Al Sheeha, Muneera
TI Human Papilloma Virus Early Proteins E6 (HPV16/18-E6) and the Cell Cycle Marker P16 (INK4a) are Useful Prognostic Markers in Uterine Cervical Carcinomas in Qassim Region- Saudi Arabia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Cervical carcinoma; HPV16/18E6; P16 (INK4a)
ID Immunohistochemistry; Cervical carcinoma; HPV16/18E6; P16 (INK4a)
AB Cervical cancer is a common and an important public health problem for adult women in developing countries. In contrast, cervical cancer incidence is low in Saudi Arabia. High-risk types of human papilloma viruses (HPV16 and HPV18) are the most significant risk factors for cervical cancer. HPV16/18-E6 oncoprotein is associated with HPV etiology, viral persistence and epithelial transformation. Cell cycle protein p16 INK4a (p16) plays an important role in the pathophysiology of cervical carcinomas. The aims of this study were to investigate the expression of HPV16/18-E6 and p16 in uterine cervical carcinomas in Qassim Region - Saudi Arabia, and to relate the results to the established clinicopathological prognostic parameters (age of the patient, educational level, birth control methods, number of pregnancy, smoking status, degree of histological differentiation, clinical stage, and lymph node metastasis) The study included 40 specimens of uterine cervical squamous cell carcinomas diagnosed and confirmed by biopsy. Histopathological classification of cervical tumors cases was performed according to the International Federation of Gynecology and Obstetrics (FIGO). Immunohistochemical analysis for HPV16/18-E6 and p16 were carried out on formalin-fixed paraffinembedded sections of cervical tissues using avidin-biotin peroxidase method. There was a significant statistical correlation between HPV16/18-E6 expression in cervical carcinoma and nationality, smoking status and size of the tumor. HPV16/ 18-E6 oncoprotein expression in normal lymphocytes and endothelial cells in the tumor tissues and the adjacent normal cervical tissues suggest the possibility that HPV infection might spread to other organs through blood circulation. P16 expression has been correlated with high grade, stage of cervical SCC and HPV16/18-E6 expression. The current study supports the critical function of p16 and HPV16/18-E6 as specific markers for cervical carcinoma. However the potential for usage of p16 and HPV16/18-E6 as prognostic markers will require detailed follow data for a larger group of patients.
C1 [Omran, Mahmoud Ola] Asyut University, Faculty of Medicine, Pathology DepartmentAssiut, Egypt.
[Al Sheeha, Muneera] Qassim University, College of Medicine, Department of Obstetrics and GynacologyBuridah, Qassim Region, Saudi Arabia.
RP Omran, MO (reprint author), Asyut University, Faculty of Medicine, Pathology Department, Assiut, Egypt.
EM ola67oh@yahoo.com
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Reijmers RM, Spaargaren M, Pals ST, 2013, Heparan sulfate proteoglycans in the control of B cell development and the pathogenesis of multiple myeloma. FEBS J 280(10):2180–2193
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 157
EP 166
DI 10.1007/s12253-014-9801-y
PG 10
ER
PT J
AU Celik, B
Khoor, A
Bulut, T
Nassar, A
AF Celik, Betul
Khoor, Andras
Bulut, Tangul
Nassar, Aziza
TI Rapid On-Site Evaluation has High Diagnostic Yield Differentiating Adenocarcinoma vs Squamous Cell Carcinoma of Non–Small Cell Lung Carcinoma, not Otherwise Specified Subgroup
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cytology; Lung carcinoma; Non-small cell lung carcinoma; On-site cytologic evaluation; Subclassification
ID Cytology; Lung carcinoma; Non-small cell lung carcinoma; On-site cytologic evaluation; Subclassification
AB Our objective was to evaluate the diagnostic yield of rapid on-site evaluation (ROSE) on the differential diagnosis of non–small cell lung carcinoma, not otherwise specified (NSCLC-NOS). Biopsied cases diagnosed as NSCLC-NOS with ROSE during 2004 through 2008 were retrieved. Diagnostic confirmation was done with immunohistochemistry (IHC) involving thyroid transcription factor-1 and p63 immunostains. For the study, 106 cases were available. The final diagnoses rendered were squamous cell carcinoma (SqCC) (n=39) and adenocarcinoma (AC) (n=67). Cytologic, histologic, and IHC concordance for these diagnoses occurred in 75 cases (70.8 %), of which 56 (52.8 %) were AC and 19 (17.9 %) were SqCC. Cytologic, histologic, and IHC discordance was found in 31 cases (29.2 %). Of these 31 cases, 11 NSCLC-NOS diagnoses histologically corresponded to 1 SqCC plus 4 ACs, and 4 favor SqCC plus 2 ACs; the former 5 NSCLC-NOS cases classified correctly through cytology, as well as IHC. However, IHC was not available for the latter 6 NSCLC-NOS cases that were also classified correctly through cytology. In addition, only 3 NSCLC-NOS diagnoses cytologically corresponded to 3 favor SqCC histologically, in which IHC was not available, and for 2 cases that both corresponded to favor SqCC and favor AC histologically and cytologically. In the other 15 cases, histology labeled 4 cases NSCLC-NOS and misclassified 2 cases; cytology labeled 1 case NSCLC-NOS and misclassified 13 cases. ROSE has high diagnostic yield over subclassification of NSCLC-NOS. We recommend allocating a cytotechnologist for specimen adequacy and a cytopathologist for cytologic diagnosis.
C1 [Celik, Betul] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Rd, 32224 Jacksonville, FL, USA.
[Khoor, Andras] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Rd, 32224 Jacksonville, FL, USA.
[Bulut, Tangul] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Nassar, Aziza] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Rd, 32224 Jacksonville, FL, USA.
RP Nassar, A (reprint author), Mayo Clinic, Department of Laboratory Medicine and Pathology, 32224 Jacksonville, USA.
EM nassar.aziza@mayo.edu
CR Travis WD, Rekhtman N, Riley GJ, Geisinger KR, Asamura H, Brambilla E et al, 2010, Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol 5(4):411–414
Agackiran Y, Ozcan A, Akyurek N, Memis L, Findik G, Kaya S, 2012, Desmoglein-3 and napsin a double stain, a useful immunohistochemical marker for differentiation of lung squamous cell carcinoma and adenocarcinoma from other subtypes. Appl Immunohistochem Mol Morphol 20(4):350–355
da Cunha Santos G, Ko HM, Saieg MA, Geddie WR, 2013, “The petals and thorns” of ROSE, rapid on-site evaluation). Cancer Cytopathol 121(1):4–8, Epub 2012 Jul 3
Collins BT, Chen AC, Wang JF, Bernadt CT, Sanati S, 2013, Improved laboratory resource utilization and patient care with the use of rapid on-site evaluation for endobronchial ultrasound fineneedle aspiration biopsy. Cancer Cytopathol 121(10):544–551, Epub 2013 Jul 3
TravisWD, Brambilla E, NoguchiM, Nicholson AG, Geisinger KR, Yatabe Y et al, 2011, International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2):244–285
Whitson BA, Groth SS, Odell DD, Briones EP, Maddaus MA, D’Cunha J et al, 2013, True negative predictive value of endobronchial ultrasound in lung cancer: are we being conservative enough? Ann Thorac Surg 95(5):1689–1694, Epub 2012 Dec 13
Dumonceau JM, Koessler T, van Hooft JE, Fockens P, 2012, Endoscopic ultrasonography-guided fine needle aspiration: relatively low sensitivity in the endosonographer population. World J Gastroenterol 18(19):2357–2363
Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T et al, 2013, Rapid on-site cytologic evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing lung cancer: a randomized study. Respiration 85(6):486–492, Epub 2013 Apr 3
Schmidt RL, Howard K, Hall BJ, Layfield LJ, 2012, The comparative effectiveness of fine-needle aspiration cytology sampling policies: a simulation study. Am J Clin Pathol 138(6):823–830
Khurana KK, Kovalovsky A,Wang D, Lenox R, 2013, Feasibility of dynamic telecytopathology for rapid on-site evaluation of endobronchial ultrasound-guided transbronchial fine needle aspiration. Telemed J E Health 19(4):265–271
Karnak D, Ciledag A, Ceyhan K, Atasoy C, Akyar S, Kayacan O, 2013, Rapid on-site evaluation and low registration error enhance the success of electromagnetic navigation bronchoscopy. Ann Thorac Med 8(1):28–32
Koegelenberg CF, Diacon AH, Irusen EM, von Groote-Bidlingmaier F, Mowlana A, Wright CA et al, 2011, The diagnostic yield and safety of ultrasound-assisted transthoracic biopsy of mediastinal masses. Respiration 81(2):134–141, Epub 2010 Dec 2
Trisolini R, Cancellieri A, Tinelli C, Paioli D, Scudeller L, Casadei GP et al, 2011, Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. Chest 139(2):395–401, Epub 2010 Oct 28
Griffin AC, Schwartz LE, Baloch ZW, 2011, Utility of on-site evaluation of endobronchial ultrasound-guided transbronchial needle aspiration specimens. Cytojournal 8:20, Epub 2011 Nov 21
Hebert-Magee S, Bae S, Varadarajulu S, Ramesh J, Frost AR, Eloubeidi MA et al, 2013, The presence of a cytopathologist increases the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration cytology for pancreatic adenocarcinoma: a meta-analysis. Cytopathology 24(3):159–171
Ecka RS, SharmaM(2013, Rapid on-site evaluation of EUS-FNAby cytopathologist: an experience of a tertiary hospital. Diagn Cytopathol 41(12):1075–1080, Epub 2013 Oct 25
NicholsonAG,GonzalezD, Shah P, PynegarMJ,DeshmukhM, Rice A et al, 2010, Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologicmaterial, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFRmutation analysis. J Thorac Oncol 5(4):436–441
Hu Y, Puri V, Crabtree TD, Kreisel D, Krupnick AS, Patterson AG et al, 2013, Attaining proficiency with endobronchial ultrasoundguided transbronchial needle aspiration. J Thorac Cardiovasc Surg 146(6):1387–1392.e1, Epub 2013 Sep 24
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 167
EP 172
DI 10.1007/s12253-014-9802-x
PG 6
ER
PT J
AU Dede, K
Salamon, F
Landherr, L
Jakab, F
Bursics, A
AF Dede, Kristof
Salamon, Ferenc
Landherr, Laszlo
Jakab, Ferenc
Bursics, Attila
TI Pathologic Assessment of Response to Chemotherapy in Colorectal Cancer Liver Metastases after Hepatic Resection: Which Method to Use?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer liver metastases; Preoperative chemotherapy; Pathologic response
ID colorectal cancer liver metastases; Preoperative chemotherapy; Pathologic response
AB Background: Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. Histopathologic assessmentmethods of the resected specimen could evaluate the response to chemotherapy. In this study it is analyzed if these histopathologic changes are specific to preoperative chemotherapy and if these methods have correlation with survival. Methods: Sixty three patients with available pathology slides, resected for colorectal cancer liver metastases were enrolled in this study. 46 patients (73 %) received neoadjuvant chemotherapy. Five pathological evaluation methods were compared according to the literature: [1] residual tumor cell ratio, [2] tumor regression grade (TRG) scoring system, [3] modified tumor regression grade (mTRG) scoring system with the type of necrosis, [4] pattern of tumor regression and [5] the tumor thickness at the tumor-normal interface (TNI). Results: Analyzing the pathological methods between the chemotherapy (CTX) and the non-chemotherapy group (NC), we found that that four evaluation methods showed significant and one showed strong correlation with the use of chemotherapy. (Residual tumor cell ratio: p=0.08; TRG: p <0.01; mTRG: p=0.03; pattern of tumor regression: p <0.01; TNI: p=0.02). In the chemotherapy group none of the analyzed pathological methods showed significant correlation with progression free survival (PFS) or with overall survival (OS). Residual tumor cell ratio, TRG and the pattern of tumor cells showed positive but not significant correlation with OS and PFS and a slight difference in the group of patients with TNI <2 mm could be documented. Conclusions: Tumor regression grade (TRG) and tumor thickness at the tumor-normal interface (TNI) were the most useful methods for pathological response evaluation and these methods had some correlation with survival. According to these data, authors concluded, that a reproducible and well defined scoring system, based on different histopathological evaluation methods should be developed to predict more accurately the effect of neoadjuvant chemotherapy in CRCLM patients.
C1 [Dede, Kristof] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Salamon, Ferenc] Fovarosi Uzsoki utcai Korhaz, PathologiaBudapest, Hungary.
[Landherr, Laszlo] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Jakab, Ferenc] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
[Bursics, Attila] Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, Uzsoki utca 29, 1145 Budapest, Hungary.
RP Dede, K (reprint author), Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Sebeszeti-Onkosebeszeti Osztaly, 1145 Budapest, Hungary.
EM dede.kristof@gmail.com
CR Nordlinger B, Vauthey J-N, Poston G et al, 2010, The timing of chemotherapy and surgery for the treatment of colorectal liver metastases. Clin Colorectal Cancer 9(4):212–218
Chua T. C., Saxena A., Liauw A., et al.: Systematic review of randomized and nonrandomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases Ann Surg Oncol. 2010, 2):492–501., 17.
Gruenberger B, Tamandl D, Schueller J et al, 2008, Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 26(11): 1830–1835
Nordlinger B, Van Cutsem E, Gruenberger T et al, 2009, Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol 20(6):985–92
Adam R, Delvart V, Pascal G et al, 2004, Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Ann Surg 240:644–657
Dede K, Mersich T, Besznyak I et al, 2013, Bevacizumab treatment before resection of colorectal liver metastases: safety, recovery of liver function, pathologic assesment. Pathol Oncol Res 19:501–508
Scoggins CR, Campbell ML, Landry CS et al, 2009, Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol 16(1):35–41
Therasse P, Arbuck SG, Eisenhauer EA et al, 2000, New guidelines to evaluate the response to treatment is solid tumors. J Natl Cancer Inst 92:205–216
ChunYS, Vauthey JN, Boonsirikamchai P et al. Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal LiverMetastases JAMA. 2 [Epub ahead of print].009 302, 21):2338–2344.
Dan G, Blazer III, Yoji K et al, 2008, Pathologic response to preoperative chemotherapy: a New outcome End point after resection of hepatic colorectal metastases. J Clin Onc 25(33):5344–5351
Rubbia-Brandt L, Giostra E, Brezault C et al, 2007, Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol 18:299–304
Chang HHI, LeeperWR, Chan G et al, 2012, Infarct-like necrosis: a distinct formof necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol 36:570–576
Ribero D, Wang H, DonadonM et al, 2007, Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110(12):2761–2767
Maru DM, Kopetz S, Boonsirikamchai P et al, 2010, Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol 34:1287–129
Gomez Dorronsoro ML, Vera R, Ortega L, et al. Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy Clin Transl Oncol. [Epub ahead of print].
Knijn N, de Ridder JA, Punt CJ et al, 2013, Histopathological evaluation of resected colorectal cancer liver metastases: what should be done? Histopathology 63(2):149–56
Ng JKS, Urbanski SJ, Mangat N et al, 2008, Colorectal liver metastases contract centripetally with a response to chemotherapy. Cancer 112:362–71
Dede K, Lang I, Porneczi B et al, 2013, Preoperative chemotherapy in the surgical treatment of colorectal liver metastases. Magy Seb 66(6):325–30
Shindoh J, Loyer EM, Kopetz S et al, 2012, Optimal morphologic response to preoperative chemotherapy: an alternate outcome End point before resection of hepatic colorectal metastases. J Clin Oncol 30:4566–4572
Egger ME, Cannon RM, Metzger TL et al, 2013, Assessment of chemotherapy response in colorectal liver metastases in patients undergoing hepatic resection and the correlation to pathologic residual viable tumor. J Am Coll Surg 216:845–56
Poultsides GA, Bao F, Servais EL et al, 2012, Pathologic response to preoperative chemotherapy in colorectal liver metastases: fibrosis, not necrosis. Predicts outcome. Ann Surg Oncol 19:2797–2804
Gruenberger T, Arnold D, Rubbia-Brandt L, 2012, Pathologic response to bevacizumab-containing chemotherapy in patients with colorectal liver metastases and its correlation with survival. Surg Oncol 21:309–15
Loupakis F, Schirripa M, CaparelloC et al.: Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab Br J Cancer. 2013. [Epub ahead of print].
Klinger M, Tamandl D, Eipeldauer S et al, 2010, Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol 17(8):2059–65
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 173
EP 179
DI 10.1007/s12253-014-9803-9
PG 7
ER
PT J
AU An, HCh
Je, ME
Yoo, JN
Lee, HS
AF An, Hyeok Chang
Je, Mi Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of Cadherin Genes DCHS2, CDH10 and CDH24 Genes in Gastric and Colorectal Cancers with High Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DHCS2; CDH10; CDH24; Cadherin; Mutation; Cancer; Microsatellite instability
ID DHCS2; CDH10; CDH24; Cadherin; Mutation; Cancer; Microsatellite instability
AB Cadherins (CDHs) are important in maintenance of cell adhesion and polarity, alterations of which contribute to tumorigenesis. Alterations of E-cadherin, a prototype CDH, have been reported in many cancers. However, alterations of unconventional CDHs, including CDH10, CDH24 and DCHS2 are largely unknown in cancers. Aim of this study was to explore whether CDH10, CDH24 and DCHS2 genes are mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that CDH10, CDH24 and DCHS2 genes had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI).We analyzed the mutations in 89GC and 131 CRC (high MSI (MSI-H) or stable MSI/low MSI (MSS/ MSI-L)) by single-strand conformation polymorphism analysis and DNA sequencing. We found six DCHS2, one CDH10 and one CDH24 frameshift mutations in them. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (8/105) and MSS/MSIL (0/115). The DCHS2 frameshift mutations were found in 8.8 % and 4.2 % of GC and CRC with MSI-H respectively. Our results show that unconventional CDH10, CDH24 and DCHS2 genes harbored frameshift mutations. These mutations might inactivate the cell adhesion-related functions and could be a feature of GC and CRC with MSI-H.
C1 [An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General SurgerySeoul, South Korea.
[Je, Mi Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Hulpiau P, van Roy F, 2009, Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol 41:349–369
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 181
EP 185
DI 10.1007/s12253-014-9804-8
PG 5
ER
PT J
AU Pula, B
Tazbierski, T
Zamirska, A
Werynska, B
Bieniek, A
Szepietowski, J
Rys, J
Dziegiel, P
Podhorska-Okolow, M
AF Pula, Bartosz
Tazbierski, Tadeusz
Zamirska, Aleksandra
Werynska, Bozena
Bieniek, Andrzej
Szepietowski, Jacek
Rys, Janusz
Dziegiel, Piotr
Podhorska-Okolow, Marzena
TI Metallothionein 3 Expression in Normal Skin and Malignant Skin Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metallothionein-3; Skin cancer; Squamous cell carcinoma; Basal cell carcinoma
ID Metallothionein-3; Skin cancer; Squamous cell carcinoma; Basal cell carcinoma
AB Metallothionein-3 (MT-3) has been shown to be expressed in several malignancies and to have an impact on patients’ survival in breast and urinary bladder cancer cases. However, its expression has not been determined in normal skin or in its malignant lesions. MT-3 expression was studied using immunohistochemistry in 17 cases of normal skin, 18 of actinic keratosis (AK), 39 of squamous cell carcinoma (SCC), and 23 of basal cell carcinoma (BCC). Low MT-3 expression was observed in normal skin epidermis with faint or no expression in the epidermis basal layer. Significantly higher MT-3 expression was noted in AK (P=0.007) and SCC (P<0.0001), as compared with normal skin epidermis. BCC cases were characterized by the lowest MT-3 expression of all the examined groups, which was significantly lower in comparison to normal skin epidermis, AK, and SCC (P=0.009; P<0.0001 and P<0.0001, respectively). In conclusion, MT-3 may be involved in the development of SCC.
C1 [Pula, Bartosz] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Tazbierski, Tadeusz] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Zamirska, Aleksandra] Wroclaw Medical University, Department of Dermatology, Venereology and AllergologyWroclaw, Poland.
[Werynska, Bozena] Medical University of Wroclaw, Department of Pulmonology and Pulmonary TumorsWroclaw, Poland.
[Bieniek, Andrzej] Wroclaw Medical University, Department of Dermatology, Venereology and AllergologyWroclaw, Poland.
[Szepietowski, Jacek] Wroclaw Medical University, Department of Dermatology, Venereology and AllergologyWroclaw, Poland.
[Rys, Janusz] Maria Sklodowska-Curie Memorial Institute Oncology Center, Department of Tumor PathologyKrakow, Poland.
[Dziegiel, Piotr] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
[Podhorska-Okolow, Marzena] Wroclaw Medical University, Department of Human Morphology and Embryology, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
RP Podhorska-Okolow, M (reprint author), Wroclaw Medical University, Department of Human Morphology and Embryology, 50-368 Wroclaw, Poland.
EM marzenna.podhorska-okolow@umed.wroc.pl
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 187
EP 193
DI 10.1007/s12253-014-9805-7
PG 7
ER
PT J
AU Tian, X
Wang, Q
Li, Y
Hu, J
Wu, L
Ding, Q
Zhang, Ch
AF Tian, Xiangguo
Wang, Qizhi
Li, Yan
Hu, Jinhua
Wu, Lei
Ding, Qian
Zhang, Chunqing
TI The Expression of S100A4 Protein in Human Intrahepatic Cholangiocarcinoma: Clinicopathologic Significance and Prognostic Value
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intrahepatic cholangiocarcinoma; Prognosis; S100A4; Matrix metalloproteinase-9 (MMP-9); Immunohistochemistry
ID Intrahepatic cholangiocarcinoma; Prognosis; S100A4; Matrix metalloproteinase-9 (MMP-9); Immunohistochemistry
AB Intrahepatic cholangiocarcinoma(ICC) is a highly malignant adenocarcinoma arising from bile duct epithelial cells of the intrahepatic biliary system with early hematogenous and lymphatic extrahepatic spread. The current treatment methods for ICC are far fromideal. Identifying novel effective prognostic biomarkers which might be related to the development and progression of ICC may help provide new therapeutic strategies. Both calcium-binding protein S100A4 and Matrix metalloproteinase-9(MMP-9) are correlated with development and progression of many carcinomas. In the present study, we investigated expression of S100A4 as well as MMP-9 in ICC tissues from 65 patients using immunohistochemistry. The correlation of S100A4 and MMP-9 expression with clinicopathological features and prognosis of patients were analyzed. S100A4 and MMP-9 were positively expressed in 32(49.2 %) and 35(53.8 %) patients, respectively. The positive correlation between S100A4 and MMP-9 expression was statistically significant (P=0.018). S100A4 positive expression was significantly correlated with vascular invasion (P=0.008), lymph node metastasis (P=0.029) and the TNM stage (P=0.008). MMP-9 expression was not found to be correlated with any clinicopathological parameter. Patients with S100A4 positive expression had a significantly poorer overall survival rate than those with S100A4 negative expression (P=0.000). MMP-9 positive expression was also correlated with poor survival (P=0.044). However, only S100A4 expression (P=0.004) and the surgical margin (P=0.024) were significantly independent prognostic predictors by multivariate analysis. In conclusion, expression of S100A4 is correlated with MMP-9 expression and it could be a useful marker for predicting the progression, metastasis and prognosis of ICC.
C1 [Tian, Xiangguo] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Wang, Qizhi] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Li, Yan] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Hu, Jinhua] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Wu, Lei] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Ding, Qian] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
[Zhang, Chunqing] Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 324 Jingwu Weiqi Road, 250021 Jinan, China.
RP Zhang, Ch (reprint author), Provincial Hospital Affiliated to Shandong University, Department of Gastroenterology, 250021 Jinan, China.
EM zhangchunqing_sdu@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 195
EP 201
DI 10.1007/s12253-014-9806-6
PG 7
ER
PT J
AU Toth-Liptak, J
Piukovics, K
Borbenyi, Z
Demeter, J
Bagdi, E
Krenacs, L
AF Toth-Liptak, Judit
Piukovics, Klara
Borbenyi, Zita
Demeter, Judit
Bagdi, Eniko
Krenacs, Laszlo
TI A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies–A Tissue Microarray Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hairy cell leukemia; Bone marrow trephine biopsy; Tissue microarray; Immunohistochemistry
ID Hairy cell leukemia; Bone marrow trephine biopsy; Tissue microarray; Immunohistochemistry
AB Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized by a unique immunophenotype. Due to low number of circulating neoplastic cells and ‘dry tap’ aspiration, the diagnosis is often based on BM trephine biopsy. We have performed a consecutive immunohistochemical analysis to evaluate diagnostic usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200, annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently available against fixation resistant epitopes. We analyzed tissue microarrays consisting of samples gained from 73 small B-cell lymphoma cases, including hairy cell leukemia (HCL) (n=32), HCL variant (HCL-v) (n=4), B-cell chronic lymphocytic leukemia (B-CLL) (n=11), lymphoplasmacytic lymphoma (LPL) (n=3), mantle cell lymphoma (MCL) (n=10), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n=2), splenic B cell marginal zone lymphoma (SMZL) (n=8), and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n=3) cases. The HCL cases were 100 % positive for all but 2 (DBA.44 and CD123) of these markers. Annexin A1 showed 100 % specificity and accuracy, which was followed by CD123, pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and TRAP, in decreasing order. In conclusion, our results reassured the high specificity of annexin A1 and pERK, as well as the diagnostic value of standard HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also represent valuable tools in the differential diagnosis of HCL and its mimics.
C1 [Toth-Liptak, Judit] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Jobb fasor 23/B, 6726 Szeged, Hungary.
[Piukovics, Klara] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Jobb fasor 23/B, 6726 Szeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, Jobb fasor 23/B, 6726 Szeged, Hungary.
RP Krenacs, L (reprint author), Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular Diagnostics, 6726 Szeged, Hungary.
EM krenacsl@vipmail.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 203
EP 211
DI 10.1007/s12253-014-9807-5
PG 9
ER
PT J
AU Magyari, F
Barna, S
Miltenyi, Zs
Rajnai, H
Csomor, J
Udvardy, M
Illes,
Varoczy, L
AF Magyari, Ferenc
Barna, Sandor
Miltenyi, Zsofia
Rajnai, Hajnalka
Csomor, Judit
Udvardy, Miklos
Illes, Arpad
Varoczy, Laszlo
TI Histopathological Difficulties in an Adolescent Lymphoma Patient
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B-cell lymphoma intermediate beetwen DLBCL and classical HL; 18FDG-PET/CT; R-CHOP; Agressive lymphomas
ID B-cell lymphoma intermediate beetwen DLBCL and classical HL; 18FDG-PET/CT; R-CHOP; Agressive lymphomas
AB The B-cell lymphoma, unclassifiable, showing intermediate features typical for both diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (HL) is a novel category of diffuse large B-cell lymphomas (DLBCL/ HL), which has been described by the WHO classification in 2008. This rare type of lymphomas, previously called as gray zone lymphoma presents peculiar clinical, morphological and immunophenotypical patterns. In December 2011 a 17-year old male was diagnosed with mixed cellularity subtype of classical HL. His clinical stage was IV/BXS (abdominal bulky) with unfavourable prognosis. Because of the unusally extended disease (nodal-extranodal-bulky) a histological revision was performed. After an incomplete course of ABVD chemotherapy the patient’s symptoms disappeared and regression was detected in the size of peripheral lymph nodes. The diagnosis changed into DLBCL/HL, so the treatment was modified to R-CHOP-14 regimen. After the administration of 3 cycles of R-CHOP-14, he achieved a complete metabolic remission (CMR), which was confirmed by a 18FDG-PET/CT scan. Receiving further 4 cycles of R-CHOP-14 therapy the patient was still in CMR, but a PET negative large mass (70× 30 mm) still remained visible in the abdominal region. Considering this residuum and the agressive subtype of lymphoma he was referred for an autologous hemopoietic stem cell transplantation (AHSCT). After 2 cycles of R-DHAP regimen, successful CD34 positive stem cell collection was performed in August 2012. In September 2012, he underwent a R-BEAM conditioning followed by AHSCT. The next 18FDG-PET/CT still detected CMR 100 days after the AHSCT. The patient was in excellent clinical condition and also in complete remission 15 months after the AHSCT. Upon this case, it should be underlined that the diagnosis may need revision if a patient represents atypical clinical signs and behavior, and the importance of cooperation between clinicians and pathologists is also strongly emphasized.
C1 [Magyari, Ferenc] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Barna, Sandor] Scanomed Kft.Debrecen, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Rajnai, Hajnalka] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Magyari, F (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, H-4032 Debrecen, Hungary.
EM magyarif13@gmail.com
CR Swerdlow S, Campo E, Harris NL et al, 2008, WHO classification of tumors of hematopoietic and lymphoid tissues. IARC, Lyon, pp 267–268
Grant C, Dunleavy K, Eberle FC et al, 2011, Primary mediastinal large B-cell lymphoma, classic hodgkin lymphoma presenting in the mediastinum, and mediastinal gray zone lymphoma: what is the oncologist to do? Curr Hematol Malig Rep 6(3):157–163
Rosenwald A,Wright G, Leroy K et al, 2003)Molecular diagnosis of primarymediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 198:851–862
Hasserjian RP, Ott G, Elenitoba-Johnson KS et al, 2009, Commentary on the WHO classification of tumors of lymphoid tissues, 2008)“Gray zone” lymphomas overlapping with Burkitt lymphoma or classicalHodgkin lymphoma. J Hematopathol 2:89–95
Dunleavy K, Grant C, Eberle FC et al, 2012, Gray-zone lymphoma: better treated like hodgkin-lymphoma or mediastinal large B-cell lymphoma. Curr Hematol Malig Rep 7:241–247
Cabanillas F, 2011, Non-Hodgkin’s lymphoma: the old and the new. Clin Lymphoma Myeloma Leuk., DOI 10.1016/j.clml.2011.03.029, Epub 2011 Apr 28
Dunleavy K, Pittaluga S, Shovlin M et al, 2011, Untreated primary mediastinal B-cell, PMBL, and mediastinal grey zone, MGZL, lymphomas: comparison of biological features and clinical outcome following DA-EPOCH-R without radiation. Ann Oncol 22(suppl 4):134
Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho D, A, and for the MabThera International Trial, MInT, Group, 2011, Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol, DOI 10.1093/annonc/mdq418
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Iwaki N, Sato Y, Kurakowa T et al, 2013, B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma. Med Mol Morphol., DOI 10.1007/s00795-013-0038-8. Epub 2013 Mar 20
Vassilakopuolos PT, Pangalis AG, Katsigiannis A et al, 2012, Rituximab, cyclophosphamide, doxorubicin, vincristin, and prednisone with or without radiotherapy in primarymediastinal large B-cell lymphoma: the emerging standard of care. Oncologist., DOI 10.1634/ theoncologist
Han HS, Escalo MP, Hsiao B et al, 2010, High incidence of falsepositive PET scans in patients with aggressive non Hodgkin lymphoma treated with rituximab containing regimen. Ann Oncol 20:309–318
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 213
EP 217
DI 10.1007/s12253-014-9810-x
PG 5
ER
PT J
AU Sun, G
Wang, Y
Liu, Q
Hu, W
AF Sun, Guogui
Wang, Yadi
Liu, Q
Hu, Wanning
TI Expression of Wip1 in Kidney Carcinoma and its Correlation with Tumor Metastasis and Clinical Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Wip1; Kidney cancer; Cell proliferation; Cell apoptosis; Prognosis
ID Wip1; Kidney cancer; Cell proliferation; Cell apoptosis; Prognosis
AB This study aimed to analyze the expression, clinical significance of proto-oncogene in kidney carcinoma and the biological effect in its cell line by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1). Immunohistochemistry and western blot were respectively used to analyze Wip1 protein expression in 78 cases of kidney cancer and normal tissues to study the relationship between Wip1 expression and clinical factors. Wip1 siRNA was transiently transfected into papillary kidney carcinoma cell by liposome-mediated method and was detected by Quantitative real-time RT-PCR (qRTPCR) and western blot.MTT assay, cell apoptosis, cell migration and invasion were also conducted as to the influence of the down-regulated expression of Wip1 that might be found on ACHN cells biological effect. The level of Wip1 protein expression was found to be significantly higher in kidney cancer tissue than normal tissues (P<0.05). There were significant differences between Wip1 expression and lymph node metastasis, clinical stages and tumor differentiation (P<0.05). Meanwhile, Increased expression of Wip1 was significantly with poor overall survival time by Kaplan-Meier analysis (P<0.05). qRT-PCR and Western blot showed that ACHN cell transfected Wip1 siRNA had a lower relative expressive content than normal cell (P<0.05).MTT assay, cell apoptosis, cell cycles demonstrated that ACHN cell transfected Wip1 siRNA had a lower survival fraction, higher cell apoptosis, more percentage of the G0/G1 phases, significant decrease in migration and invasion, and higher P53 and P16 protein expression compared with ACHN cell untransfected Wip1 siRNA (P<0.05). Wip1 protein was increased in kidney carcinoma, specifically in T stages, lymph node metastasis, clinical stages and tumor differentiation. Wip1 may involved in the biological processes of kidney cancer cell proliferation, apoptosis, and migration and invasion by regulation P53 and P16 protein expression.
C1 [Sun, Guogui] Tangshan People’s Hospital, Department of Chemoradiotherapy, NO.65, Shengli Road, Lunan District, 063000 Tangshan, Hebei Province, China.
[Wang, Yadi] The Military General Hospital of Beijing PLA, Department of Radiotherapy, 100700 Beijing, China.
[Liu, Q] The Fourth Hospital of Hebei Medical University, Department of Radiotherapy, 050017 Shijiazhuang, China.
[Hu, Wanning] Tangshan People’s Hospital, Department of Chemoradiotherapy, NO.65, Shengli Road, Lunan District, 063000 Tangshan, Hebei Province, China.
RP Hu, W (reprint author), Tangshan People’s Hospital, Department of Chemoradiotherapy, 063000 Tangshan, China.
EM guogui_sun@hotmail.com
CR Tan X, He S, Han Y, Yu Y, Xiao J, Xu D, Wang G, Du Y, Chang W, Yin J, Su T, Hou J, Cao G, 2013, Establishment and characterization of clear cell renal cell carcinoma cell lines with different metastatic potential from Chinese patients. Cancer Cell Int 13:20
StadlerWM, Figlin RA,McDermott DF, Dutcher JP, Knox JJ,Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM, 2010, ARCCS Study Investigators: safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access programinNorthAmerica. Cancer 116:1272–1280
Fuku T, Semba S, Yutori H, Yokozaki H, 2007, Increased wild-type p53-induced phosphatase 1, Wip1 or PPM1D, expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma. Pathol Int 57:566–571
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 219
EP 224
DI 10.1007/s12253-014-9811-9
PG 6
ER
PT J
AU Je, ME
Choi, JY
Yoo, JN
Lee, HS
AF Je, Mi Eun
Choi, Jin Youn
Yoo, Jin Nam
Lee, Hyung Sug
TI Oncogenic PTPN11 Mutations are Rare in Solid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Je, Mi Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Pugh TJ,Morozova O, Attiyeh EF, Asgharzadeh S,Wei JS, Auclair D, Carter SL, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, Chiu R, Corbett RD, Hirst M, Jackman SD, Kamoh B, Khodabakshi AH, Krzywinski M, Lo A, Moore RA, Mungall KL, Qian J, Tam A, Thiessen N, Zhao Y, Cole KA, Diamond M, Diskin SJ, Mosse YP, Wood AC, Ji L, Sposto R, Badgett T, LondonWB,Moyer Y, Gastier-Foster JM, Smith MA, Guidry Auvil JM, Gerhard DS, Hogarty MD, Jones SJ, Lander ES, Gabriel SB, Getz G, Seeger RC, Khan J,MarraMA, Meyerson M, Maris JM, 2013, The genetic landscape of high-risk neuroblastoma. Nat Genet 45:279–84
Chan G, Kalaitzidis D, Neel BG, 2008, The tyrosine phosphatase Shp2, PTPN11, in cancer. Cancer Metastasis Rev 27:179–92
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YooNJ, KimHR, KimYR, An CH, Lee SH, 2012, Somaticmutations of the KEAP1 gene in common solid cancers. Histopathology 60:943– 52
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–7
Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG, 2004, Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res 64:8816–20
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2015
VL 21
IS 1
BP 225
EP 227
DI 10.1007/s12253-014-9780-z
PG 3
ER
PT J
AU Bianco, MA
Uno, M
Oba-Shinjo, MS
Clara, AC
de Almeida Galatro, FTh
Rosemberg, S
Teixeira, JM
Nagahashi Marie, KS
AF Bianco, Macedo Andre
Uno, Miyuki
Oba-Shinjo, Mieko Sueli
Clara, Afonso Carlos
de Almeida Galatro, Fernanda Thais
Rosemberg, Sergio
Teixeira, Jacobsen Manoel
Nagahashi Marie, Kazue Suely
TI CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemokine; Astrocytoma; CXCR7; CXCR4; HIF1α; IDH1
ID Chemokine; Astrocytoma; CXCR7; CXCR4; HIF1α; IDH1
AB The CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1α expression and IDH1 mutation. CXCR7, CXCR4 and HIF1α mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p<0.001). AGII showed no significant correlation between CXCR7/HIF1α (p=0.548); there was significant correlation between CXCR7/CXCR4 (p=0.042) and CXCR7/IDH1 (p=0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p<0.001) and CXCR7/HIF1α (p=0.008). HIF1α overexpression was associated with higher expressions of CXCR7 (p=0.01) and CXCR4 (p<0.0001), while IDH1 mutation was associated with lower CXCR7 (p=0.009) and CXCR4 (p=0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1α in GBM. Overexpression HIF1α was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.
C1 [Bianco, Macedo Andre] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
[Uno, Miyuki] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
[Oba-Shinjo, Mieko Sueli] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
[Clara, Afonso Carlos] Barretos Cancer Hospital, Rua Antenos Duarte Villela, 1331, 14784-400 Barretos, SP, Brazil.
[de Almeida Galatro, Fernanda Thais] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
[Rosemberg, Sergio] Sao Paulo University School of Medicine, Department of Pathology, Av. Dr. Arnaldo, 455, 01246-903 Sao Paulo, SP, Brazil.
[Teixeira, Jacobsen Manoel] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
[Nagahashi Marie, Kazue Suely] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, 01246-903 Sao Paulo, SP, Brazil.
RP Bianco, MA (reprint author), University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell Biology, 01246-903 Sao Paulo, Brazil.
EM abianco@usp.br;amb0973@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 229
EP 240
DI 10.1007/s12253-014-9813-7
PG 12
ER
PT J
AU Ascencio-Cedillo, R
Lopez-Pulido, IE
Munoz-Valle, FJ
Villegas-Sepulveda, N
Del Toro-Arreola, S
Estrada-Chavez, C
Daneri-Navarro, A
Franco-Topete, R
Perez-Montiel, D
Garcia-Carranca, A
Pereira-Suarez, LA
AF Ascencio-Cedillo, Rafael
Lopez-Pulido, Ivan Edgar
Munoz-Valle, Francisco Jose
Villegas-Sepulveda, Nicolas
Del Toro-Arreola, Susana
Estrada-Chavez, Ciro
Daneri-Navarro, Adrian
Franco-Topete, Ramon
Perez-Montiel, Delia
Garcia-Carranca, Alejandro
Pereira-Suarez, Laura Ana
TI Prolactin and Prolactin Receptor Expression in Cervical Intraepithelial Neoplasia and Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Prolactin; Prolactin receptor; Expression
ID Cervical cancer; Prolactin; Prolactin receptor; Expression
AB Prolactin receptor (PRLR) overexpression could play a role in tumorigenesis. The aim of this study was to determine prolactin (PRL) and PRLR expression in biopsies from patients with precursor lesions and uterine cervical cancer. PRLR expression was analyzed in 63 paraffin-embedded biopsies of uterine cervical tissue. In total, eleven low-grade squamous intraepithelial lesions (LSIL), 23 high-grade squamous intraepithelial lesions (HSIL), 21 uterine cervical cancers (UCC) and 8 normal epithelium (NE) were examined using immunoperoxidase staining and Western blot analysis. Additionally, PRL expression was identified in human cervical cancer serumand tissues. The PRLR expressionwas found to be significantly increased in cervical cancer in comparison with normal tissue and precursor lesions (P<0.0003). The presence of the long isoform of the PRLR was observed only in cervical cancer tissues. Serum PRL levels were normal in all samples and local prolactin expression was similar in precursor lesions and cervical cancer by Western blot analysis. Our data suggest a possible role for PRLR in the progression of cervical cancer.
C1 [Ascencio-Cedillo, Rafael] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de FisiologiaGuadalajara, Jalisco, Mexico.
[Lopez-Pulido, Ivan Edgar] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de FisiologiaGuadalajara, Jalisco, Mexico.
[Munoz-Valle, Francisco Jose] Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Instituto de Investigacion en Ciencias BiomedicasGuadalajara, Jalisco, Mexico.
[Villegas-Sepulveda, Nicolas] Unidad Zacatenco, Centro de Investigacion y de Estudios Avanzados-IPN, Departamento de Biomedicina Molecular, 07360 Mexico City, DF, Mexico.
[Del Toro-Arreola, Susana] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de FisiologiaGuadalajara, Jalisco, Mexico.
[Estrada-Chavez, Ciro] Centro de Investigacion y Asistencia en Tecnologia y diseno del Estado de Jalisco A.C., 44270 Guadalajara, Jalisco, Mexico.
[Daneri-Navarro, Adrian] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de FisiologiaGuadalajara, Jalisco, Mexico.
[Franco-Topete, Ramon] Nuevo Hospital Civil de Guadalajara, Departamento de PatologiaGuadalajara, Jalisco, Mexico.
[Perez-Montiel, Delia] Instituto de Investigaciones Biomedicas UNAM, Departamento de Biologia Molecular y BiotecnologiaMexico City, Mexico.
[Garcia-Carranca, Alejandro] Instituto de Investigaciones Biomedicas UNAM, Departamento de Biologia Molecular y BiotecnologiaMexico City, Mexico.
[Pereira-Suarez, Laura Ana] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de FisiologiaGuadalajara, Jalisco, Mexico.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 241
EP 246
DI 10.1007/s12253-014-9814-6
PG 6
ER
PT J
AU Vizkeleti, J
Vereczkey, I
Frohlich, G
Varga, Sz
Horvath, K
Pulay, T
Pete, I
Nemeskeri, Cs
Mayer,
Sipos, N
Kasler, M
Polgar, Cs
AF Vizkeleti, Julia
Vereczkey, Ildiko
Frohlich, Georgina
Varga, Szilvia
Horvath, Katalin
Pulay, Tamas
Pete, Imre
Nemeskeri, Csaba
Mayer, Arpad
Sipos, Norbert
Kasler, Miklos
Polgar, Csaba
TI Pathologic Complete Remission after Preoperative High-Dose-Rate Brachytherapy in Patients with Operable Cervical Cancer: Preliminary Results of a Prospective Randomized Multicenter Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Preoperative brachytherapy; Pathologic complete remission; Surgical margins
ID Cervical cancer; Preoperative brachytherapy; Pathologic complete remission; Surgical margins
AB The role of preoperative intrauterine brachytherapy (BT) in the multidisciplinary treatment of early stage cervical carcinoma (ESCC) is controversial. In 2005, a prospective randomized multicenter study was initiated in Hungary in order to explore the potential advantages of preoperative high-dose-rate (HDR) BT. In this article we evaluate the efficiency of preoperative HDR BT by the rate of pathologic complete remission (pCR) in the first 185 patients enrolled in the study at the National Institute of Oncology and at the Uzsoki Municipal Cancer Center in collaboration with the 1st Department of Gynaecology and Obstetrics of Semmelweis University, Budapest, Hungary. In arm A, patients received 2x8Gy preoperative intracavitary HDR BT, while in arm B no preoperative treatment was given. In both arms patients underwent radical Wertheim (Piver III) hysterectomy. The pCR rate was 25.7% after preoperative HDR BT, while it was only 11.2% with surgery alone (p=0.03), in these cases the tumor was eliminated during the diagnostic excision or conisation. The rate of positive surgical margins was 1.5% after preoperative BT, while it was as high as 11.4% without preoperative RT (p=0.02). There was no significant difference in the local tumor control (LTC), distant metastases free survival (DMFS) and overall survival (OS) between the two arms. According to our preliminary results preoperative intracavitary HDR BT significantly increases the rate of pCR and decreases the rate of positive surgical margins in patients with ESCC. Longer follow-up is required to establish the possible impact of pCR on the ultimate LTC and OS.
C1 [Vizkeleti, Julia] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Vereczkey, Ildiko] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Frohlich, Georgina] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Varga, Szilvia] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Horvath, Katalin] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Pulay, Tamas] National Institute of Oncology, Center of GynaecologyBudapest, Hungary.
[Pete, Imre] National Institute of Oncology, Center of GynaecologyBudapest, Hungary.
[Nemeskeri, Csaba] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Mayer, Arpad] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Sipos, Norbert] Semmelweis Medical University, Ist Department of Gynaecology and ObstetricsBudapest, Hungary.
[Kasler, Miklos] National Institute of OncologyBudapest, Hungary.
[Polgar, Csaba] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
RP Vizkeleti, J (reprint author), National Institute of Oncology, Center of Radiotherapy, Budapest, Hungary.
EM juliavizkeleti@yahoo.com
CR Practice Bulletin ACOG, 2002, Diagnosis and treatment of cervical carcinomas. Int J Gynec Obst 78:79–91
NCCN Clinical Practice Guidelines in Oncology-Cervical Cancer, 2011, www.nccn.org/
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Atlan D, Touboul E, Deniaud-Alexandre E et al, 2002, Operable stages IB and II cervical carcinomas: A retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy. Int J Radiat Oncol Biol Phys 54:780–793
Beskow C, Agren-Cronqvist AK, Granath F et al, 2002, Pathologic complete remission after preoperative intracavitary radiotherapy of cervical cancer stage Ib and IIa is a strong prognostic factor for longterm survival: Analysis of the Radiumhemmet data 1989–1991. Int J Gynecol Cancer 12:158–170
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Muschitz S, Petrow P, Briot E et al, 2004, Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma. Radiother Oncol 73:187–194
Resbeut MR, Alzieu C, Gonzague-Casabianca L et al, 2001, Combined brachytherapy and surgery for early carcinoma of the uterine cervix: Analysis of extent of surgery on outcome. Int J Radiat Oncol Biol Phys 50:873–881
Mayer A, Nemeskeri C, Poti Z, 2004, Evaluation of high-doserate brachytherapy in the preoperative treatment of FIGO stage IB cervical carcinoma. Magyar Onkologia [In Hungarian] 48: 141–144
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 247
EP 256
DI 10.1007/s12253-014-9815-5
PG 10
ER
PT J
AU Hu, YM
Li, J
Yu, LCh
Shi, ShB
Du, YJ
Wu, JN
Shi, LW
AF Hu, Yi-Ming
Li, Jing
Yu, Li-Chao
Shi, Shun-Bing
Du, Yong-Jie
Wu, Jian-Nong
Shi, Lin Wei
TI Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Neoadjuvant chemotherapy; Survivin mRNA; Prognosis; Prediction
ID Non-small cell lung cancer; Neoadjuvant chemotherapy; Survivin mRNA; Prognosis; Prediction
AB In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by realtime quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P=0.01 and P=0.008, respectively) and pathologic response (both P=0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P=0.021 and P=0.014, respectively for DFS; P=0.009 and P=0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.
C1 [Hu, Yi-Ming] Affiliated Hospital of Jiangsu University, Department of Pulmonary Medicine, 438 North Jiefang Street, 212001 Zhenjiang, China.
[Li, Jing] Affiliated Hospital of Jiangsu University, Department of Pulmonary Medicine, 438 North Jiefang Street, 212001 Zhenjiang, China.
[Yu, Li-Chao] Affiliated Hospital of Jiangsu University, Department of Thoracic Surgery, 212001 Zhenjiang, China.
[Shi, Shun-Bing] Affiliated Hospital of Jiangsu University, Department of Thoracic Surgery, 212001 Zhenjiang, China.
[Du, Yong-Jie] Affiliated Hospital of Jiangsu University, Department of Pulmonary Medicine, 438 North Jiefang Street, 212001 Zhenjiang, China.
[Wu, Jian-Nong] Affiliated Hospital of Jiangsu University, Department of Pathology, 212001 Zhenjiang, China.
[Shi, Lin Wei] Affiliated Hospital of Jiangsu University, Department of Pulmonary Medicine, 438 North Jiefang Street, 212001 Zhenjiang, China.
RP Li, J (reprint author), Affiliated Hospital of Jiangsu University, Department of Pulmonary Medicine, 212001 Zhenjiang, China.
EM lijian541226@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 257
EP 265
DI 10.1007/s12253-014-9816-4
PG 9
ER
PT J
AU Shen, CC
Cui, XY
He, Y
Kang, YH
Yi, Ch
Yang, JL
Gou, LT
AF Shen, Cong-Cong
Cui, Xin-Yi
He, Yi
Kang, Yu-Huan
Yi, Cheng
Yang, Jin-Liang
Gou, Lan-Tu
TI High Phosphorylation Status of AKT/mTOR Signal in DESI2-Reduced Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DESI2; AKT; mTOR; Pancreatic ductal adenocarcinoma
ID DESI2; AKT; mTOR; Pancreatic ductal adenocarcinoma
AB Desumoylating isopeptidase 2 (DESI2) is a recently identified protein with unclear functions. In this study, a total of 132 tissue samples of pancreatic ductal adenocarcinoma and 73 samples of pancreatic normal tissues were explored to assess DESI2 expression and its implications to AKT/ mTOR signal. Immunohistochemistry showed DESI2 expression is significantly decreased in cancer tissues versus normal tissues, presenting lowest level in poorly differentiated cancer. Unlike DESI2, the key factors in AKT/mTOR pathway including p-AKT, mTOR, p-mTOR and p-P70S6K present high expression in pancreatic cancer. It is notable that p-mTOR is significantly increased in DESI2-lower cancer compared with DESI2-higher cancer, although mTOR presents no difference in the two groups. The relative p-mTOR/mTOR ratio is also significantly elevated in DESI2-lower cancer. Moreover, the samples whose p-AKT and p-mTOR scores both exceed the median are obviously increased in DESI2-lower cancer compared with DESI2-higher cancer. As a downstream molecule of AKT/mTOR pathway, p-P70S6K was found to display higher level in DESI2-lower pancreatic cancer. High phosphorylation status of those proteins in DESI2-reduced pancreatic cancer indicates that there is high activity of AKT/mTOR signal in condition of DESI2 reduction, which could provide clues to reveal the implications of DESI2 in carcinogenesis.
C1 [Shen, Cong-Cong] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, No. 1, Keyuan Road 4, Gaopeng Street, 610041 Chengdu, Sichuan, China.
[Cui, Xin-Yi] Sichuan University, West China Hospital, Division of Abdominal Cancer, Cancer Center, 610041 Chengdu, Sichuan, China.
[He, Yi] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, No. 1, Keyuan Road 4, Gaopeng Street, 610041 Chengdu, Sichuan, China.
[Kang, Yu-Huan] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, No. 1, Keyuan Road 4, Gaopeng Street, 610041 Chengdu, Sichuan, China.
[Yi, Cheng] Sichuan University, West China Hospital, Division of Abdominal Cancer, Cancer Center, 610041 Chengdu, Sichuan, China.
[Yang, Jin-Liang] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, No. 1, Keyuan Road 4, Gaopeng Street, 610041 Chengdu, Sichuan, China.
[Gou, Lan-Tu] Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, No. 1, Keyuan Road 4, Gaopeng Street, 610041 Chengdu, Sichuan, China.
RP Gou, LT (reprint author), Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, 610041 Chengdu, China.
EM goulantu@gmail.com
CR Gregory SG, Barlow KF,McLay KE, Kaul R, Swarbreck D,Dunham A, 2006, The DNA sequence and biological annotation of human chromosome 1. Nature 441:315–321
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 267
EP 272
DI 10.1007/s12253-014-9817-3
PG 6
ER
PT J
AU Pavlakis, K
Bobos, M
Batistatou, A
Kotoula, V
Eleftheraki, GA
Stofas, A
Timotheadou, E
Pentheroudakis, G
Psyrri, A
Koutras, A
Pectasides, D
Papakostas, P
Razis, E
Christodoulou, Ch
Kalogeras, TK
Fountzilas, G
AF Pavlakis, Kitty
Bobos, Mattheos
Batistatou, Anna
Kotoula, Vassiliki
Eleftheraki, G Anastasia
Stofas, Anastasios
Timotheadou, Eleni
Pentheroudakis, George
Psyrri, Amanda
Koutras, Angelos
Pectasides, Dimitrios
Papakostas, Pavlos
Razis, Evangelia
Christodoulou, Christos
Kalogeras, T Konstantine
Fountzilas, George
TI p85 Protein Expression is Associated with Poor Survival in HER2-Positive Patients with Advanced Breast Cancer Treated with Trastuzumab
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p85; Prognostic factors; Breast carcinoma; Immunohistochemistry; HER2 status; Trastuzumab
ID p85; Prognostic factors; Breast carcinoma; Immunohistochemistry; HER2 status; Trastuzumab
AB To investigate the immunohistochemical expression of p85 in a cohort of trastuzumab-treated HER2- positive and HER2-negative metastatic breast cancer patients. The medical records of all patients with metastatic breast cancer treated with trastuzumab-based regimens between 1998 and 2010 were reviewed and clinical information was obtained. Formalin-fixed paraffin-embedded tumor tissue samples with adequate material were retrospectively collected from 183 patients. Samples were evaluated by immunohistochemistry for p85, estrogen receptors (ER), progesterone receptors (PgR), HER2, Ki67, PTEN and phosphorylated Akt (S473 and T308). HER2 status was studied by fluorescence in situ hybridization, as well. PIK3CA mutational status was also evaluated. Median follow-up for all patients was 72 months. Central re-evaluation for HER2 revealed only 111 HER2- positive cases, with the remaining 72 patients being HER2- negative. Median survival was longer in HER2-positive patients (50.7 months) compared to HER2-negative patients (36.6 months) both treated with trastuzumab, but this difference has not reached significance (p=0.068). In total, 62 % of the patients were found positive for p85, however the p85 protein was not found to be differentially expressed in HER2- positive versus HER2-negative cases. There were no significant associations between protein expression of p85 and any of the markers under study, or with time to progression. Positive p85 protein expression was however associated with poor survival in trastuzumab-treated HER2-positive patients. In our cohort of trastuzumab-treated HER2-positive breast cancer patients, positive p85 protein expression appears to be a prognostic factor of poor survival and, if validated, might have important implications in the treatment of such patients.
C1 [Pavlakis, Kitty] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Bobos, Mattheos] Aristotle University of Thessaloniki School of Medicine, Hellenic Foundation for Cancer Research, Laboratory of Molecular OncologyThessaloniki, Greece.
[Batistatou, Anna] Ioannina University Hospital, Department of PathologyIoannina, Greece.
[Kotoula, Vassiliki] Aristotle University of Thessaloniki, AHEPA University Hospital, Pathology DepartmentThessaloniki, Greece.
[Eleftheraki, G Anastasia] Data Office, Hellenic Cooperative Oncology Group, Section of BiostatisticsAthens, Greece.
[Stofas, Anastasios] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Timotheadou, Eleni] Aristotle University of Thessaloniki School of Medicine, Department of Medical OncologyThessaloniki, Greece.
[Pentheroudakis, George] Ioannina University Hospital, Department of Medical OncologyIoannina, Greece.
[Psyrri, Amanda] Attikon University Hospital, Second Department of Internal MedicineAthens, Greece.
[Koutras, Angelos] University of Patras Medical School, University Hospital, Division of Oncology, Department of MedicinePatras, Greece.
[Pectasides, Dimitrios] Attikon University Hospital, Second Department of Internal MedicineAthens, Greece.
[Papakostas, Pavlos] University of Athens, 3rd Department of Medicine, Oncology UnitAthens, Greece.
[Razis, Evangelia] University of Athens, 3rd Department of Medicine, Oncology UnitAthens, Greece.
[Christodoulou, Christos] Second Department of Medical OncologyPiraeus, Greece.
[Kalogeras, T Konstantine] Aristotle University of Thessaloniki School of Medicine, Department of Medical OncologyThessaloniki, Greece.
[Fountzilas, George] Aristotle University of Thessaloniki School of Medicine, Hellenic Foundation for Cancer Research, Laboratory of Molecular OncologyThessaloniki, Greece.
RP Pavlakis, K (reprint author), University of Athens, Medical School, Department of Pathology, Athens, Greece.
EM epavlaki@med.uoa.gr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 273
EP 282
DI 10.1007/s12253-014-9818-2
PG 10
ER
PT J
AU Sun, G
Zhang, J
Ma, BX
Wang, Y
Cheng, JY
Hu, W
AF Sun, Guogui
Zhang, Jianguo
Ma, B X
Wang, Yadi
Cheng, J Y
Hu, Wanning
TI Overexpression of Wild-Type p53-Induced Phosphatase 1 Confers Poor Prognosis of Patients with Nasopharyngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Wip1; Nasopharyngeal cancer; Cell proliferation; Cell apoptosis; Prognosis
ID Wip1; Nasopharyngeal cancer; Cell proliferation; Cell apoptosis; Prognosis
AB This study aimed to analyze the expression, clinical significance of proto-oncogene in nasopharyngeal carcinoma and the biological effect in its cell line by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1). Immunohistochemistry and western blot were respectively used to analyze Wip1 protein expression in 85 cases of nasopharyngeal cancer and normal tissues to study the relationship between Wip1 expression and clinical factors. Wip1 siRNA was transiently transfected into papillary nasopharyngeal carcinoma cell by liposome-mediated method and was detected by Quantitative real-time RT-PCR (qRT-PCR) and western blot. MTT-assay, cell apoptosis, migration and invasion were also conducted as to the influence of the down-regulated expression of Wip1 that might be found on CNE2 cells biological effect. The level of Wip1 protein expression was found to be significantly higher in nasopharyngeal cancer tissue than normal tissues (P <0.05). There were significant differences between Wip1 expression and T stages, lymph node metastasis, clinical stages, tumor differentiation and radiotherapy response (P<0.05), regardless of age, gender (P>0.05). Meanwhile, Increased expression of Wip1 was significantly with poor overall survival time by Kaplan- Meier analysis (P<0.05). Wip1 expression deletion determines independent risk factors for prognosis of patients with nasopharyngeal carcinoma in addition to tumor T stage, clinical stage, histological grade and lymph node metastasis outside by Cox-2 in the regression analysis (P<0.05). qRT-PCR and Western blot showed that CNE2 cell transfected Wip1 siRNA had a lower relative expressive content than normal cell (P<0.05). MTT assay, cell apoptosis, cell cycles demonstrated that CNE2 cell transfected Wip1 siRNA had a lower survival fraction, higher cell apoptosis, more percentage of the G0/G1 phases, significant decrease in migration and invasion, and higher P53 and P16 protein expression compared with CNE2 cell untransfected Wip1 siRNA (P<0.05).Wip1 protein was increased in nasopharyngeal carcinoma, specifically in T stages, lymph node metastasis, clinical stages and tumor differentiation. Wip1 may involved in the biological processes of nasopharyngeal cancer cell proliferation, apoptosis, and migration and invasion by regulation P53 and P16 protein expression.
C1 [Sun, Guogui] Tangshan People’s Hospital, Department of Chemoradiotherapy, NO.65, Shengli road, Lunan district, 063000 Tangshan, Hebei province, China.
[Zhang, Jianguo] Tangshan People’s Hospital, Department of Pathology, 063000 Tangshan, Hebei province, China.
[Ma, B X] Tangshan People’s Hospital, Department of Pathology, 063000 Tangshan, Hebei province, China.
[Wang, Yadi] The Military General Hospital of Beijing PLA, Department of Radiotherapy, 100700 Beijing, China.
[Cheng, J Y] The Fourth Hospital of Hebei Medical University, Department of Radiotherapy, 050017 Shijiazhuang, China.
[Hu, Wanning] Tangshan People’s Hospital, Department of Chemoradiotherapy, NO.65, Shengli road, Lunan district, 063000 Tangshan, Hebei province, China.
RP Hu, W (reprint author), Tangshan People’s Hospital, Department of Chemoradiotherapy, 063000 Tangshan, China.
EM wanning_hu2008@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 283
EP 291
DI 10.1007/s12253-014-9819-1
PG 9
ER
PT J
AU Nourashrafeddin, S
Aarabi, M
Modarressi, HM
Rahmati, M
Nouri, M
AF Nourashrafeddin, Seyedmehdi
Aarabi, Mahmoud
Modarressi, Hosein Mohammad
Rahmati, Marveh
Nouri, Mohammad
TI The Evaluation of WBP2NL-Related Genes Expression in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; WBP2NL-related genes; qRT-PCR
ID Breast cancer; WBP2NL-related genes; qRT-PCR
AB Breast cancer is the most frequent cause of mortality in women all around the world; therefore, study on molecular aspects of breast cancer is necessary for finding new biomarkers. Recent studies have shown that WW Binding Protein 2 (WBP2) is an important protein for the oncogenic property of cancer. We have previously evaluated the WW Binding Protein 2 N-Terminal Like (WBP2NL) gene expression in cancerous cell line and breast tumor tissues, and reported changes in expression, which could increase tumorigenic cell growth. However, the molecular mechanisms of WBP2NL and its clinical relevance have not been investigated. In this study, the expression of WBP2NL-related genes in the invasive breast carcinoma and normal breast tissues was evaluated for the first time. Analysis of WBP2NL-related genes expression was performed with reverse transcription-PCR and real time-PCR detection method. The target genes studied were as follow: WW domain containing E3 ubiquitin protein ligase 1(WWP1),membrane associated guanylatekinase containing WW and PDZ domain-1 (MAGI1), neural precursor cell expressed developmentally down-regulated 4 (NEDD4), formin binding protein-4 (FNBP4), BCL2-associated athanogene-3 (BAG3), WW domain-containing oxidoreductase (WWOX), yes-associated protein-1 (YAP1), WW domain containing transcription regulator (WWTR1), member RAS oncogene family (RAB2A), and small G protein signaling modulator 3 (SGSM3). The expression of WWP1, BAG3, and WWTR1 was significantly increased in breast cancer. In contrast, the expression of WWOX, YAP1, RAB2A, and SGSM3 was significantly decreased. The MAGI1 and NEDD4 expression was increased, while the expression of FNBP4 was unchanged. These findings lead us to suggest that WBP2NL might play roles as an antiapoptotic factor or co-activator to promote breast cancer cell survival and proliferation.
C1 [Nourashrafeddin, Seyedmehdi] Tabriz University of Medical Sciences, Women’s Reproductive Health Research CenterTabriz, Iran.
[Aarabi, Mahmoud] Queen’s University, Department of Anatomy and Cell BiologyKingston, Canada.
[Modarressi, Hosein Mohammad] Tehran University of Medical Sciences, Faculty of Medicine, Department of Medical GeneticsTehran, Iran.
[Rahmati, Marveh] Tabriz University of Medical Science, Faculty of Medicine, Department of BiochemistryTabriz, Iran.
[Nouri, Mohammad] Tabriz University of Medical Sciences, Women’s Reproductive Health Research CenterTabriz, Iran.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 293
EP 300
DI 10.1007/s12253-014-9820-8
PG 8
ER
PT J
AU Tang, JY
Hsi, E
Huang, YCh
Hsu, ChHN
Yang, WCh
Chang, HW
Chai, ChY
Chu, PY
AF Tang, Jen-Yang
Hsi, Edward
Huang, Ya-Chun
Hsu, Chung-Heng Nicholas
Yang, Wen-Chi
Chang, Hsueh-Wei
Chai, Chee-Yin
Chu, Pei-Yi
TI Overexpression of Autophagy-Related 16-Like 1 in Patients with Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autophagy; Oral cancer; Immunohistochemistry; Autophagy-related 16-like 1
ID Autophagy; Oral cancer; Immunohistochemistry; Autophagy-related 16-like 1
AB Dyregulation of autophagy has been reported in various human cancers including oral squamous cell carcinoma (OSCC). The objective of this study was to link expression of autophagy-related 16-like 1 (ATG16L1), a protein essential for autophagosome formation, to clinical outcome in a cohort of 90 OSCC patients. Expression level of ATG16L1 was assessed by immunohistochemistry and an immunoreactivity score (IRS), ranging from 0 to 9, was assigned to each case. The results were correlated with clinicopathological parameters and outcome of patients. Twenty-seven patients (30 %) exhibited ATG16L1 overexpression as indicated by an IRS of 9. Overexpression of ATG16L1 was significantly associated with disease stage (p=0.001), size (p=0.031) of the tumor, lymph node metastasis (p=0.004), and histological grade (p=0.038). ATG16L1 overexpression significantly affected the overall survival (p=0.020) and time to recurrence (p=0.031) of OSCC patients in Kaplan- Meier analysis. The present study suggested that ATG16L1 may be used as a biomarker for selecting OSCC patients with a more aggressive phenotype.
C1 [Tang, Jen-Yang] Kaohsiung Medical University, Faculty of Medicine, College of Medicine, Department of Radiation OncologyKaohsiung, Taiwan, Republic of China.
[Hsi, Edward] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Huang, Ya-Chun] Kaohsiung Medical University, College of Medicine, Department of Pathology, No. 100, Tzyou 1st RoadKaohsiung, Taiwan, Republic of China.
[Hsu, Chung-Heng Nicholas] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Yang, Wen-Chi] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Chang, Hsueh-Wei] Kaohsiung Medical University, College of Medicine, Research Center for Environmental MedicineKaohsiung, Taiwan, Republic of China.
[Chai, Chee-Yin] Kaohsiung Medical University, College of Medicine, Department of Pathology, No. 100, Tzyou 1st RoadKaohsiung, Taiwan, Republic of China.
[Chu, Pei-Yi] St. Martin De Porres Hospital, Department of Pathology, No. 565, Sec. 2, Daya RoadNew Taipei City, Taiwan, Republic of China.
RP Chai, ChY (reprint author), Kaohsiung Medical University, College of Medicine, Department of Pathology, Kaohsiung, Taiwan, Republic of China.
EM cychai@kmu.edu.tw
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 301
EP 305
DI 10.1007/s12253-014-9821-7
PG 5
ER
PT J
AU Mostowska, A
Sajdak, S
Pawlik, P
Markowska, J
Pawalowska, M
Lianeri, M
Jagodzinski, PP
AF Mostowska, Adrianna
Sajdak, Stefan
Pawlik, Piotr
Markowska, Janina
Pawalowska, Monika
Lianeri, Margarita
Jagodzinski, P Pawel
TI Replication Study for the Association of Seven Genome- Gwas-Identified Loci With Susceptibility to Ovarian Cancer in the Polish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; Single nucleotide polymorphisms; Genome-wide association studies
ID Ovarian cancer; Single nucleotide polymorphisms; Genome-wide association studies
AB We investigated the previously-demonstrated association of seven genome-wide association studies (GWAS) single nucleotide polymorphisms (SNPs), including rs2072590 (HOXD-AS1), rs2665390 (TIPARP), rs10088218 and rs10098821 (8q24), rs3814113 (9p22), rs9303542 (SKAP1) and rs2363956 (ANKLE1), as risk factors of epithelial ovarian tumors (EOTs). These SNPs were genotyped in two hundred seventy three patients with EOTs and four hundred sixty four unrelated healthy females from the Polish population. We observed the lowest p values of the trend test for the 9p22 rs3814113 and 8q24 rs10098821 SNPs in patients with all subtypes of ovarian cancer (ptrend=0.010 and ptrend=0.014, respectively). There were also significant p values for the trend of the 9p22 rs3814113 and the 8q24 rs10098821 SNPs for serous histological subtypes of ovarian cancer (ptrend=0.006, ptrend=0.033, respectively). Moreover, stratification of the patients based on their histological type of cancer demonstrated, in the dominant hereditary model, a significant association of the 9p22 rs3814113 SNP with serous ovarian carcinoma OR=0.532 (95 % CI=0.342 - 0.827, p=0.005, pcorr=0.035). Despite the relatively small sample size of cases and controls, our studies confirmed some of the previously-demonstrated GWAS SNPs as genetic risk factors for EOTs.
C1 [Mostowska, Adrianna] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Sajdak, Stefan] Poznan University of Medical Sciences, Clinic of Gynecological SurgeryPoznan, Poland.
[Pawlik, Piotr] Poznan University of Medical Sciences, Clinic of Gynecological SurgeryPoznan, Poland.
[Markowska, Janina] Poznan University of Medical Sciences, Chair of Gynecologic OncologyPoznan, Poland.
[Pawalowska, Monika] Poznan University of Medical Sciences, Chair of Gynecologic OncologyPoznan, Poland.
[Lianeri, Margarita] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Jagodzinski, P Pawel] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
RP Jagodzinski, PP (reprint author), Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznan, Poland.
EM pjagodzi@am.poznan.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 307
EP 313
DI 10.1007/s12253-014-9822-6
PG 7
ER
PT J
AU Dedic Plavetic, N
Jakic-Razumovic, J
Kulic, A
Sirotkovic-Skerlev, M
Baric, M
Vrbanec, D
AF Dedic Plavetic, Natalija
Jakic-Razumovic, Jasminka
Kulic, Ana
Sirotkovic-Skerlev, Maja
Baric, Marina
Vrbanec, Damir
TI Prognostic Value of Ki-67 in Breast Carcinoma: Tissue Microarray Method Versus Whole Section Analysis- Potentials and Pitfalls
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ki-67; Breast cancer; Proliferation; Prognostic factor; Tissue microarrays
ID Ki-67; Breast cancer; Proliferation; Prognostic factor; Tissue microarrays
AB In our study we have compared the prognostic value of two distinct methods of immunohistochemical Ki- 67 determination, tissue microarray (TMA) and classical whole section analysis. "Cut-off" values were used according to the 2009 St. Gallen Consensus. Tissue specimens were obtained from a consecutive retrospective series of 215 female patients with primary invasive tumours. Two hundred and thirteen patients were included in the study. Data on Ki-67 was collected by both tissue microarray (TMA) and whole section analysis. Follow up data on overall (OS) and diseasefree survival (DFS) were collected. Median follow-up was 95 months (range from 7.8 through 107 months). Mutual correlation of two Ki-67 determination methods was nonsignificant (Person’s r=0.13417; p=0.0528). There was statistically significant association of whole section Ki-67 expression with histological and nuclear grade, progesterone receptor and HER2/neu status. The expression of Ki-67 protein in TMAs correlated only with histological and nuclear grade, but not with other traditional clinicopathological factors. Statistically significant differences in DFS (p=0.0156) and OS (p=0.0028) were confirmed between subgroups with low and high whole section Ki-67 expression. When subgroups with high and intermediate expression were compared, significant difference was found in DFS (p=0.0272), but not in OS (p=0.0624). On the other hand, there was no statistically significant difference either in DFS, or in OS, according to the expression of Ki-67 in TMAs (p=0.6529; p= 0.7883; p=0.7966 for DFS, and p=0.8917; p=0.6448; p=0.4323 for OS, respectively). In our study, classical whole section was superior to TMA analysis in terms of prognosis and clinicopathological correlation. Our results indicate that the method used may have impact on prognostic significance of Ki-67. Further studies are needed, covering a greater number of patients and including a precisely defined stage and treatment patient cohorts, in order to solve controversies in Ki-67 assessment methodology.
C1 [Dedic Plavetic, Natalija] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Jakic-Razumovic, Jasminka] University Hospital Center Zagreb, Department of PathologyZagreb, Croatia.
[Kulic, Ana] University Hospital Center Zagreb and Zagreb Medical School, Department of PathophysiologyZagreb, Croatia.
[Sirotkovic-Skerlev, Maja] University Hospital Center Zagreb and Zagreb Medical School, Department of PathophysiologyZagreb, Croatia.
[Baric, Marina] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Vrbanec, Damir] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
RP Dedic Plavetic, N (reprint author), University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, 10 000 Zagreb, Croatia.
EM natalija.dedic-plavetic@zg.t-com.hr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 315
EP 324
DI 10.1007/s12253-014-9823-5
PG 10
ER
PT J
AU Han, BE
Chang, YB
Jung, SY
Kim, YS
AF Han, Byeol Eun
Chang, Yoon Bo
Jung, Suk Young
Kim, Yeon Sung
TI Lantana camara Induces Apoptosis by Bcl-2 Family and Caspases Activation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Bcl-2 family; Breast cancer; Caspase; Lantana camara
ID Apoptosis; Bcl-2 family; Breast cancer; Caspase; Lantana camara
AB Breast cancer is one of the most common cancers worldwide, and the second most fatal cancer in women after lung cancer. Because there are instances of cancer resistance to existing therapies, studies focused on the identification of novel therapeutic drugs are very important. In this study, we identified a natural anticancer agent from Lantana camara, a flowering plant species of the genus Verbena. The extract obtained from the L. camara exhibited cell death properties in the human breast cancer cell line,MCF-7.We found that the apoptosis induced by treatment with the L. camara extract was regulated by the Bcl-2 family. Bid and Bax was increased and Bcl-2 was decreased by L. camara extract. L. camara extract modulated cleavage of caspase-8, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP). Our results support the potential use of the L. camara extract as an anti-breast cancer drug.
C1 [Han, Byeol Eun] Wonkwang University, College of Pharmacy, Institute of Pharmaceutical Research and Development, 460 Ikandae-ro, 570-749 Iksan, Jeonbuk, South Korea.
[Chang, Yoon Bo] Wonkwang University, College of Pharmacy, Institute of Pharmaceutical Research and Development, 460 Ikandae-ro, 570-749 Iksan, Jeonbuk, South Korea.
[Jung, Suk Young] Pusan National University, College of PharmacyBusan, South Korea.
[Kim, Yeon Sung] Wonkwang University, College of Pharmacy, Institute of Pharmaceutical Research and Development, 460 Ikandae-ro, 570-749 Iksan, Jeonbuk, South Korea.
RP Kim, YS (reprint author), Wonkwang University, College of Pharmacy, Institute of Pharmaceutical Research and Development, 570-749 Iksan, South Korea.
EM sungykim@wonkwang.ac.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 325
EP 331
DI 10.1007/s12253-014-9824-4
PG 7
ER
PT J
AU Cincin, BZ
Unlu, M
Kiran, B
Bireller, SE
Baran, Y
Cakmakoglu, B
AF Cincin, Birsu Zeynep
Unlu, Miray
Kiran, Bayram
Bireller, Sinem Elif
Baran, Yusuf
Cakmakoglu, Bedia
TI Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon Cancer; Quercitrin; Antiproliferative; Apoptosis
ID Colon Cancer; Quercitrin; Antiproliferative; Apoptosis
AB Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.
C1 [Cincin, Birsu Zeynep] Istanbul University, Institute of Experimental Medical Research, CapaIstanbul, Turkey.
[Unlu, Miray] Izmir Institute of Technology, Science Faculty, Department of Molecular Biology and Genetics, Urla, 35430 Izmir, Turkey.
[Kiran, Bayram] Kastamonu University, Department of BiologyKastamonu, Turkey.
[Bireller, Sinem Elif] Istanbul University, Institute of Experimental Medical Research, CapaIstanbul, Turkey.
[Baran, Yusuf] Izmir Institute of Technology, Science Faculty, Department of Molecular Biology and Genetics, Urla, 35430 Izmir, Turkey.
[Cakmakoglu, Bedia] Istanbul University, Institute of Experimental Medical Research, CapaIstanbul, Turkey.
RP Cakmakoglu, B (reprint author), Istanbul University, Institute of Experimental Medical Research, Istanbul, Turkey.
EM bedia@istanbul.edu.tr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 333
EP 338
DI 10.1007/s12253-014-9825-3
PG 6
ER
PT J
AU Zidi, S
Stayoussef, M
Zouidi, F
Benali, S
Gazouani, E
Mezlini, A
Yacoubi-Loueslati, B
AF Zidi, Sabrina
Stayoussef, Mouna
Zouidi, Ferjeni
Benali, Samir
Gazouani, Ezzedine
Mezlini, Amel
Yacoubi-Loueslati, Besma
TI Tumor Necrosis Factor Alpha (−238 / −308) and TNFRII-VNTR (−322) Polymorphisms as Genetic Biomarkers of Susceptibility to Develop Cervical Cancer Among Tunisians
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumor necrosis factor; Polymorphisms; Cervical cancer; Tunisians; Haplotypes
ID Tumor necrosis factor; Polymorphisms; Cervical cancer; Tunisians; Haplotypes
AB Host genetic factors may confer susceptibility to Cervical Cancer. TNF-α as pro-inflammatory cytokine participates in the maintenance of immune homeostasis. Allelic variation of immuno-modulatory genes is associated with alteration in immune function. This study investigated the associations between TNF-α-308G>A, −238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women. Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The variant heterozygote −308 G/A was associated with a 41 % decreased risk of cervical cancer (GG vs A/A; p=0.002; OR = 0.41; 95 % CI =0.23–0.76). Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was significantly associated with a decreased risk of CC (GG vs G/A+A/A; p=0.026; OR = 0.62; 95 % CI = 0.40–0.97). The FIGO stratified analysis showed that the minor variant A/A and combined G/A+A/A of TNFα-238 G>A and TNFα-308 G>A increased the risk of the tumor evolution, respectively, (P=0.011; OR = 2.98; 95% CI = 1.16–7.72) (P=0.008; OR = 2.76; 95%CI = 1.20–6.41), (P=0.000; OR = 16.33; 95 % CI = (5.10–55.23) (P=0.000; OR = 7.54; 95 % CI = 2.68–22.29). There was statistically significant relationship between the incidence of the TNF-α mutations and the clinical progression of cancer according to the FIGO classification. In our study, the haploview analysis revealed no LD between rs1800629 and rs361525. TNF-α and TNFRII polymorphisms might be genetic risk factors for cervical cancer in Tunisian population
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Stayoussef, Mouna] University of Monastir, Faculty of Pharmacy, Research Unit of Hematological and Autoimmune DiseasesMonastir, Tunisia.
[Zouidi, Ferjeni] Habib Bourguiba University, Hospital of Sfax, Immunology DepartmentSfax, Tunisia.
[Benali, Samir] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Gazouani, Ezzedine] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Yacoubi-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 339
EP 345
DI 10.1007/s12253-014-9826-2
PG 7
ER
PT J
AU Mise, PB
Telesmanic, DV
Tomic, S
Sundov, D
Capkun, V
Vrdoljak, E
AF Mise, Petric Branka
Telesmanic, Dobric Vesna
Tomic, Snjezana
Sundov, Dinka
Capkun, Vesna
Vrdoljak, Eduard
TI Correlation Between E-cadherin Immunoexpression and Efficacy of First Line Platinum-Based Chemotherapy in Advanced High Grade Serous Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; E-cadherin; Immunohistochemistry; Response to platinum-based chemotherapy; Platinum sensitivity; Prognosis
ID Ovarian cancer; E-cadherin; Immunohistochemistry; Response to platinum-based chemotherapy; Platinum sensitivity; Prognosis
AB To analyze correlation between immunoexpression of E-cadherin and efficacy of first line platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma. The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed, paraffinembedded samples from 98 patients with advanced-stage high-grade serous ovarian cancer and related to clinical features (stage according to the International Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial cytoreductive surgery), response to platinum-based chemotherapy (according to Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinum-resistant and platinum-sensitive) and patients progression free survival (PFS) and overall survival (OS). Ecadherin immunostaining was positive in 74 and negative in 24 serous ovarian carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive E-cadherin expression predict significantly better response to first line platinum-based chemotherapy (p<0.001) and platinum sensitivity (p<0.001). Moreover, positive E-cadherin expression predict significantly longer PFS (p<0.001) and OS (p<0.001). The multivariate analysis for OS showed that positive E-cadherin expression is predictor to platinum sensitivity (p<0.001) and longer OS (p=0.01). Positive E-cadherin expression seems to be a predictor of better response to first line platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative Ecadherin expression was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin as a marker has predictive and prognostic value.
C1 [Mise, Petric Branka] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, Spinciceva 1, 21000 Split, Croatia.
[Telesmanic, Dobric Vesna] General Hospital Zadar, Department of Oncology, Boze Pericica 5, 23000 Zadar, Croatia.
[Tomic, Snjezana] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21000 Split, Croatia.
[Sundov, Dinka] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Pathology, Forensic Medicine and Cytology, Spinciceva 1, 21000 Split, Croatia.
[Capkun, Vesna] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Nuclear Medicine, Spinciceva 1, 21000 Split, Croatia.
[Vrdoljak, Eduard] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, Spinciceva 1, 21000 Split, Croatia.
RP Mise, PB (reprint author), University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, 21000 Split, Croatia.
EM brapemi@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 347
EP 356
DI 10.1007/s12253-014-9827-1
PG 10
ER
PT J
AU Coban, I
Cakir, A
Unal, DKT
Bassullu, N
Karpuz, V
Dogusoy, BG
Alper, M
AF Coban, Ipek
Cakir, Asli
Unal, Dilay Kokenek Tuba
Bassullu, Nuray
Karpuz, Vildan
Dogusoy, Bulbul Gulen
Alper, Murat
TI Emerin Expression in Well Differentiated Epithelial Lesions of Thyroid: Implications in Papillary Thyroid Carcinoma Diagnosis and Predicting Malignant Behavior
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Emerin; Thyroid; Nucleus; Membrane
ID Emerin; Thyroid; Nucleus; Membrane
AB Recently, it has been reported that identifying nuclear membrane irregularities with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis. However, literature regarding the significance of emerin immunohistochemistry in thyroid is limited. We evaluated the diagnostic accuracy of the well-established nuclear alterations, nuclear protrusions and recently described nuclear shapes (garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin- eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy measures of tissue microarrays evaluated with both stains, to detect whether emerin immunohistochemistry improves the diagnostic accuracy for papillary thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin- eosin diagnostic accuracy of grooves was the highest (0.92). For follicular variant of papillary thyroid carcinoma, with both stains, predominately oval nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95). Nuclear protrusions were poor identifiers for papillary thyroid carcinoma. However, with emerin immunohistochemistry, they could successfully identify malignancy in 83 % of the cases. Using emerin immunohistochemistry, in addition to hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70 vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs. 0.94). Consistent with the previous literature, our findings indicate that emerin immunohistochemistry may be used as an adjunct diagnostic method to identify papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions detected with emerin imunohistochemistry may be used as indicators of malignant behavior in small tissue samples of thyroid.
C1 [Coban, Ipek] Istanbul Bilim University, School of Medicine, Department of Pathology, Cemil Aslan Guder Sok. No: 8 Gayrettepe, 30342 Istanbul, Turkey.
[Cakir, Asli] Medipol University School of Medicine, Department of PathologyIstanbul, Turkey.
[Unal, Dilay Kokenek Tuba] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Bassullu, Nuray] Istanbul Bilim University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Karpuz, Vildan] Istanbul Bilim University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Dogusoy, Bulbul Gulen] Istanbul Bilim University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Alper, Murat] Diskapi Yildirim Beyazit Education and Research Hospital, Department of PathologyAnkara, Turkey.
RP Coban, I (reprint author), Istanbul Bilim University, School of Medicine, Department of Pathology, 30342 Istanbul, Turkey.
EM ipekco@gmail.com;ipek.coban@florence.com.tr
CR Clary KM, Condel JL, Liu Y, Johnson DR, Grzybicki DM, Raab SS, 2005, Interobserver variability in the fine needle aspiration biopsy diagnosis of follicular lesions of the thyroid gland. Acta Cytol 49(4): 378–382
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 357
EP 366
DI 10.1007/s12253-014-9828-0
PG 10
ER
PT J
AU Hu, Q
Luo, T
He, P
Zhong, X
Tian, T
Lv, Q
Yan, X
Zheng, H
AF Hu, Qiancheng
Luo, Ting
He, Ping
Zhong, Xiaorong
Tian, Tinglun
Lv, Qing
Yan, Xi
Zheng, Hong
TI Trends and Present Treatment Patterns of Early Breast Cancer in Southwest China
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Early breast cancer; Southwest China; Trends; Present treatment
ID Early breast cancer; Southwest China; Trends; Present treatment
AB To analyze the changing patterns of treatment and to explore the current treatment approaches for breast cancer in Southwest China, we conducted a population-based retrospective cohort study of early breast cancer cases. The data of patients who registered in the information management system for breast cancer in Huaxi Hospital, Sichuan University from 1989 to 2012 were extracted. Nearly all patients underwent surgery, among whom radical mastectomy was the predominant option. Chemotherapy (88.7 %) was the most predominant adjuvant therapy approach. The percentage of patients receiving radiation therapy displayed fluctuant increase, which was 37.1 % in 2001 and reached up to 67.6 % in 2011. Besides, the endocrinetherapy became more and more popular in the hormone-receptor positive patients and the percentage of endocrinetherapywas increased from54.1 at 2001 to 85.6 % at 2011. However, more than 10 % of hormone-receptor positive patients still did not receive endocrinetherapy annually. The hormone-receptor positive patients who received endocrinetherapy had better 5-year disease free survival (DFS) and overall survival (OS) compared to those without endocrinetherapy (5-y DFS: 88.4% vs. 75.1 %, P<0.001; 5-y OS: 95.7 % vs. 88.4 %, P<0.001). N stage appeared to have greater impact on the 5-year DFS and OS than molecular subtyping. The treatment for breast cancer in China has been significantly improved but more attentions should be paid to radiotherapy and endocrine therapy. In addition, the value of N stage in the prognosis of breast cancer should not be ignored when the molecular typing draws more and more attentions.
C1 [Hu, Qiancheng] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[Luo, Ting] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[He, Ping] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[Zhong, Xiaorong] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[Tian, Tinglun] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[Lv, Qing] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Yan, Xi] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
[Zheng, Hong] West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, No.37 Guo Xue Xiang, 610041 Chengdu, China.
RP Zheng, H (reprint author), West China Hospital, Sichuan University, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, 610041 Chengdu, China.
EM hongzheng11@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 367
EP 378
DI 10.1007/s12253-014-9829-z
PG 12
ER
PT J
AU Ibrahim, RT
Abdel-Raouf, MS
AF Ibrahim, R Taiseer
Abdel-Raouf, M Samar
TI Immunohistochemical Study of Glypican-3 and HepPar-1 in Differentiating Hepatocellular Carcinoma from Metastatic Carcinomas in FNA of the Liver
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HCC; MA; Fine needle aspiration; Glypican-3; GPC-3; HepPar-1; Immunohistochemistry
ID HCC; MA; Fine needle aspiration; Glypican-3; GPC-3; HepPar-1; Immunohistochemistry
AB Hepatocellular carcinoma (HCC) remains a common malignant cancer worldwide, it is considered the fifth most common malignant cancer. On the other hand,metastatic tumors are widespread in the liver , with metastatic adenocarcinoma (MA) constituting the greatest part, therefore differentiation of HCC from MA is a frequent problem facing the pathologist especially in liver fine-needle aspiration biopsies. Evaluating the diagnostic value of glypican-3 (GPC-3) and HepPar-1 immunostaining in differentiating hepatocellular carcinoma from metastatic tumors in liver cell block material. Fourty eight cell blocks prepared from FNA from the liver ( 30 cases HCC, 18 cases metastatic carcinoma in liver ) stained by Glypican -3 and HepPar-1 immunohistochemical markers. Glypican-3 was immunoexpressed in 97 % of cases of HCC while all cases of metastatic carcinoma were negative . HepPar-1 was expressed in 93 % of cases of HCC and 11 % of metastatic carcinoma of the liver . In this study the sensitivity of GPC3 in the diagnosis of HCC in cytological material was 96.7% and the specificity was 100% while the sensitivity and specificity of HepPar-1 was 93.3 % and 88.9 % respectively. Immunohistochemical staining for GPC-3 in cell block material of the liver is highly sensitive and specific and it is a valuable tool capable of differentiating HCC from most of metastatic tumors of the liver.
C1 [Ibrahim, R Taiseer] Zagazig University, Faculty of Medicine, Department of PathologyAl Sharqiyah, Egypt.
[Abdel-Raouf, M Samar] Zagazig University, Faculty of Medicine, Department of PathologyAl Sharqiyah, Egypt.
RP Abdel-Raouf, MS (reprint author), Zagazig University, Faculty of Medicine, Department of Pathology, Al Sharqiyah, Egypt.
EM samar_foda2010@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 379
EP 387
DI 10.1007/s12253-014-9830-6
PG 9
ER
PT J
AU Yong, Z
Zhang, Q
Fan, Z
Sun, J
Liu, X
Cheng, L
Li, A
Xu, J
AF Yong, Zhang
Zhang, Qiang
Fan, Zhongze
Sun, Jue
Liu, Xulin
Cheng, Lingling
Li, Ao
Xu, Jianhua
TI A Chinese herbal Formula, Chang-Wei-Qin, Synergistically Enhances Antitumor Effect of Oxaliplatin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Xenograft model; Changweiqing; Platinum drugs; Copper transporters
ID Colorectal cancer; Xenograft model; Changweiqing; Platinum drugs; Copper transporters
AB Chang-Wei-Qing (CWQ), a Chinese herbal formula, has long been employed clinically to treat cancers. In this study, we investigated the synergistic effect of CWQ with oxaliplatin (OXA) on the tumor growth inhibition of orthotopic transplanted colon cancer and explored the underlying mechanism. By generating the orthotopic transplanted nude mouse model of human colon carcinoma, we found that (1) CWQ enhanced OXA-mediated tumor suppression by 4.25-fold. (2) The body weights of nude mice in CWQ group and combination group were increased. (3) The survival time of tumor-bearing nude mice was dramatically improved in CWQ and CWQ/OXA group. (4) CWQ could restore OXA-mediated deregulation of copper transporter genes, hCTR1, ATP7A and ATP7B. (5) OXA-induced drug resistance index for OXA, 5-FU, HCPT and THP were 7.59, 4.28, 5.78 and 4.50 respectively, while the reversal index by combined CWQ treatment were 6.57, 2.61, 4.97 and 3.10, respectively. Our study demonstrates that the repeated intraperitoneal injection of OXA can induce multi-drug resistance of orthotopic transplanted nude mouse model of human colon carcinoma. The CWQ treatment can alleviate OXA-triggered side effects and reverse platinum drug resistance via up-regulation of hCTR1 expression and down-regulation of ATP7A and ATP7B levels.
C1 [Yong, Zhang] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Zhang, Qiang] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Fan, Zhongze] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Sun, Jue] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Liu, Xulin] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Cheng, Lingling] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Li, Ao] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
[Xu, Jianhua] Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 164 Lanxi Road, Putuo District, 200062 Shanghai, China.
RP Xu, J (reprint author), Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Department of Medical Oncology, 200062 Shanghai, China.
EM xujianhua_2013@126.com;xujianhua50@126.com
CR Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA. Cancer J Clin 61(2):69–90
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Shiragami R,Murata S, Kosugi C, Tezuka T, YamazakiM, Hirano A, Yoshimura Y, Suzuki M, Shuto K, Koda K, 2013, Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells. Int J Oncol 43(2):431–438
McCleary NJ, Odejide O, Szymonifka J, Ryan D, Hezel A, Meyerhardt JA, 2013, Safety and effectiveness of oxaliplatin-based chemotherapy regimens in adults 75 years and older with colorectal cancer. Clin Colorectal Cancer 12(1):62–69
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Dmitriev OY, 2011, Mechanism of tumor resistance to cisplatin mediated by the copper transporter ATP7B. Biochem Cell biol= Biochimie et biologie cellulaire 89(2):138––147
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KuoMT, Fu S, Savaraj N, Chen HH, 2012, Role of the human highaffinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy. Cancer Res 72(18): 4616–4621
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Howell SB, Safaei R, Larson CA, Sailor MJ, 2010, Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs. Mol Pharmacol 77(6):887–894
Komatsu M, Sumizawa T, Mutoh M, Chen ZS, Terada K, Furukawa T, Yang XL, Gao H, Miura N, Sugiyama T et al, 2000, Copper-transporting P-type adenosine triphosphatase, ATP7B, is associated with cisplatin resistance. Cancer Res 60(5):1312–1316
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Kummar S, Copur MS, Rose M, Wadler S, Stephenson J, O’Rourke M, Brenckman W, Tilton R, Liu SH, Jiang Z et al, 2011, A phase I study of the chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer 10(2):85–96
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 389
EP 397
DI 10.1007/s12253-014-9831-5
PG 9
ER
PT J
AU Docs, O
Fazakas, F
Horvath, LN
Toth, L
Andras, Cs
Horvath, Zs
Mehes, G
AF Docs, Otto
Fazakas, Ferenc
Horvath, Lugosine Nora
Toth, Laszlo
Andras, Csilla
Horvath, Zsolt
Mehes, Gabor
TI Changes of KRAS Exon 2 Codon 12/13 Mutation Status in Recurrent Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE KRAS; Colorectal carcinoma; Heterogeneity; Multiple tumors
ID KRAS; Colorectal carcinoma; Heterogeneity; Multiple tumors
AB Colorectal cancer (CRC) is a heterogeneous disease presenting with a wide spectrum of morphological and molecular characteristics sometimes even within the same patient. To understand the mechanisms of oscillations in the KRAS status we evaluated the collective of CRC patients tested using allele-specific PCR and Sanger-sequencing. Mutant KRAS allele was observed in 43.3 % of cases. Repeated analysis of KRAS status in recurrent tumors ormetastases was performed in 18/665 cases and a total of 6 cases with different KRAS status was found. In three cases the histological pattern of the tumor was identical. In one patient different histology and molecular status was seen between the primary and the recurrent tumor samples. In two further cases localization, histological type and KRAS mutational status all supported the occurrence of synchron/metachron colorectal tumors. In conclusion, both the progression of the original disease but also multiple tumor formation may contribute to mutation status differences during the course of colorectal carcinoma.
C1 [Docs, Otto] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Fazakas, Ferenc] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Horvath, Lugosine Nora] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Andras, Csilla] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Horvath, Zsolt] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Mehes, G (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4032 Debrecen, Hungary.
EM gabor.mehes@med.unideb.hu;gabor.mehes@dote.hu
CR Baselga J, 2001, The EGFR as a target for anticancer therapy – focus on cetuximab. Eur J Cancer 37:16–22
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 399
EP 404
DI 10.1007/s12253-014-9834-2
PG 6
ER
PT J
AU Satapathy, RSh
Mohapatra, P
Das, D
Siddharth, S
Kundu, NCh
AF Satapathy, Ranjan Shakti
Mohapatra, Purusottam
Das, Dipon
Siddharth, Sumit
Kundu, Nath Chanakya
TI The Apoptotic Effect of Plant Based Nanosilver in Colon Cancer Cells is a p53 Dependent Process Involving ROS and JNK Cascade
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Silver nanoparticle; Periwinkle; p53; MAPK; MMP; ROS; Colon cancer
ID Silver nanoparticle; Periwinkle; p53; MAPK; MMP; ROS; Colon cancer
AB Here, we report the p53 dependent mitochondriamediated apoptotic mechanism of plant derived silvernanoparticle (PD-AgNPs) in colorectal cancer cells (CRCs). PD-AgNPs was synthesized by reduction of AgNO3 with leaf extract of a medicinal plant periwinkle and characterized. Uptake of PD-AgNPs (ξ - 2.52±4.31 mV) in HCT116 cells was 3 fold higher in comparison to synthetic AgNPs (ξ + 2.293±5.1 mV). A dose dependent increase in ROS production, activated JNK and decreased mitochondrial membrane potential (MMP) were noted in HCT116 but not in HCT116 p53−/− cells after PD-AgNP exposure. PD-AgNP-mediated apoptosis in CRCs is a p53 dependent process involving ROS and JNK cascade.
C1 [Satapathy, Ranjan Shakti] KIIT University, KIIT School of Biotechnology, Cancer Biology Division, Campus-11, Patia, Bhubaneswar, 751024 Orissa, India.
[Mohapatra, Purusottam] KIIT University, KIIT School of Biotechnology, Cancer Biology Division, Campus-11, Patia, Bhubaneswar, 751024 Orissa, India.
[Das, Dipon] KIIT University, KIIT School of Biotechnology, Cancer Biology Division, Campus-11, Patia, Bhubaneswar, 751024 Orissa, India.
[Siddharth, Sumit] KIIT University, KIIT School of Biotechnology, Cancer Biology Division, Campus-11, Patia, Bhubaneswar, 751024 Orissa, India.
[Kundu, Nath Chanakya] KIIT University, KIIT School of Biotechnology, Cancer Biology Division, Campus-11, Patia, Bhubaneswar, 751024 Orissa, India.
RP Kundu, NCh (reprint author), KIIT University, KIIT School of Biotechnology, Cancer Biology Division, 751024 Orissa, India.
EM cnkundu@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 405
EP 411
DI 10.1007/s12253-014-9835-1
PG 7
ER
PT J
AU Todorova, AT
Jordanov, HS
Stancheva, SG
Chalakov, JI
Melnicharov, BM
Kunev, VK
Mitev, IV
Kaneva, PR
Goranova, ET
AF Todorova, A Teodora
Jordanov, H Stanislav
Stancheva, S Gergana
Chalakov, J Ivan
Melnicharov, B Mincho
Kunev, V Kuncho
Mitev, I Vanio
Kaneva, P Radka
Goranova, E Teodora
TI Mutational Status of CDKN2A and TP53 Genes in Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CDKN2A; TP53; Mutations; Sequencing; Laryngeal squamous cell carcinoma
ID CDKN2A; TP53; Mutations; Sequencing; Laryngeal squamous cell carcinoma
AB Laryngeal squamous cell carcinoma (LSCC) is the second most common tumour of the head and neck. It is characterized by frequent aberrations in two cell-cycle regulators— CDKN2A and TP53. However, LSCC has been often studied as a part of the group of head and neck cancers and not as an individual entity. In the current study we aimed to examine mutation status of CDKN2A and TP53 genes in 108 LSCC patients. DNA was extracted from fresh-frozen tumour tissues; exons 1–3 of CDKN2A and exons 5–8 of TP53 were screened for mutations by direct sequencing. Genetic aberrations in CDKN2A were found in 16 (14.2 %) and those in TP53—in 56/108 (51.9 %) tumours. Seven mutations (two insertions, three deletions, one missense and one silent) detected in CDKN2Awere not described previously. Also, we found seven novel deletions and a novel indel in TP53. No significant associations with clinical features were found. However, TP53 mutations were predominantly observed in smokers with advanced stage tumours. Screening for genetic aberrations in a defined group of LSCC contributes to the knowledge about laryngeal carcinogenesis. Further investigations are required to confirm the observed trends in associations with clinical features.
C1 [Todorova, A Teodora] Medical University of Sofia, Molecular Medicine Center, 2 Zdrave street, 1431 Sofia, Bulgaria.
[Jordanov, H Stanislav] Medical University - Sofia, Clinic of Otorhinolaryngology, UMHAT, 8 Byalo More Street, 1527 Sofia, Bulgaria.
[Stancheva, S Gergana] Medical University of Sofia, Molecular Medicine Center, 2 Zdrave street, 1431 Sofia, Bulgaria.
[Chalakov, J Ivan] Medical University - Sofia, Clinic of Otorhinolaryngology, UMHAT, 8 Byalo More Street, 1527 Sofia, Bulgaria.
[Melnicharov, B Mincho] Medical University - Sofia, Clinic of Otorhinolaryngology, UMHAT, 8 Byalo More Street, 1527 Sofia, Bulgaria.
[Kunev, V Kuncho] Medical University - Sofia, Clinic of Otorhinolaryngology, UMHAT, 8 Byalo More Street, 1527 Sofia, Bulgaria.
[Mitev, I Vanio] Medical University of Sofia, Molecular Medicine Center, 2 Zdrave street, 1431 Sofia, Bulgaria.
[Kaneva, P Radka] Medical University of Sofia, Molecular Medicine Center, 2 Zdrave street, 1431 Sofia, Bulgaria.
[Goranova, E Teodora] Medical University of Sofia, Molecular Medicine Center, 2 Zdrave street, 1431 Sofia, Bulgaria.
RP Goranova, ET (reprint author), Medical University of Sofia, Molecular Medicine Center, 1431 Sofia, Bulgaria.
EM goranova@mmcbg.org
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 413
EP 421
DI 10.1007/s12253-014-9836-0
PG 9
ER
PT J
AU Podmaniczky, E
Fabian, K
Papay, J
Puskas, R
Gyulai, M
Furak, J
Tiszlavicz, L
Losonczy, Gy
Timar, J
Moldvay, J
AF Podmaniczky, Eszter
Fabian, Katalin
Papay, Judit
Puskas, Rita
Gyulai, Marton
Furak, Jozsef
Tiszlavicz, Laszlo
Losonczy, Gyorgy
Timar, Jozsef
Moldvay, Judit
TI Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ERCC1; Lung cancer; Platinumbased chemotherapy; Immunohistochemistry; Gender differences
ID ERCC1; Lung cancer; Platinumbased chemotherapy; Immunohistochemistry; Gender differences
AB We have already demonstrated in a small cohort of 17 non-small cell lung cancer patients that ERCC1 (excision repair cross-complementation group 1) protein expression decreased after platinum-based treatment, however, certain clinicopathological parameters, such as histologic subtypes, ERCC1 expression scores, chemotherapeutic combinations, response rate, gender and smoking history were not analyzed. The aim of our present study was to extend the studied cohort and analyze those parameters. ERCC1 protein expression was examined in 46 patients treated with neoadjuvant chemotherapy. 46 bronchoscopic biopsy samples (27 squamous cell carcinomas /SCC/ and 19 adenocarcinomas /ADC/) together with their corresponding surgical biopsies were studied. ERCC1 immunohistochemistry was performed on formalinfixed, paraffin-embedded tissues. Staining scores were calculated by multiplying the percentage of positive tumor cells (0–100) by the staining intensity (0–3). 24/27 bronchoscopic SCC tissues expressed ERCC1. Thirteen of these cases became negative after neoadjuvant therapy and the expression differences between pre- and postchemotherapy samples were highly significant (p<0.001). 11/19 bronchoscopic ADC tissues expressed ERCC1. Six of these cases became negative after neoadjuvant therapy and the expression differences were significant (p<0.010). There was no newly expressed ERCC1 postoperatively. Comparison of staining score changes revealed more pronounced decrease in SCC (p=0.032). We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender. We could confirm our previous data in a larger cohort that platinum-based chemotherapy affects the ERCC1 expression probably referring to an induction of tumor cell selection.
C1 [Podmaniczky, Eszter] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
[Fabian, Katalin] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
[Papay, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Puskas, Rita] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
[Gyulai, Marton] County Hospital of PulmonologyTorokbalint, Hungary.
[Furak, Jozsef] Szegedi Tudomanyegyetem, AOK, Mellkassebeszeti TanszekSzeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of PathologySzeged, Hungary.
[Losonczy, Gyorgy] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Moldvay, Judit] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
RP Fabian, K (reprint author), Semmelweis University, Department of Pulmonology, H-1125 Budapest, Hungary.
EM drfabian.katalin@gmail.com
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Guarneri V, DieciMV, Barbieri E, Piacentini F, Omarini C, Ficarra G, Bettelli S, Conte PF, 2013, Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients. Ann Oncol., DOI 10.1093/annonc/mdt364
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 423
EP 431
DI 10.1007/s12253-014-9839-x
PG 9
ER
PT J
AU Saadat, M
Saadat, Sh
AF Saadat, Mostafa
Saadat, Shekoofeh
TI Genetic Polymorphism of CAT C-262 T and Susceptibility to Breast Cancer, a Case–Control Study and Meta-Analysis of the Literatures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; CAT; Genetic polymorphism; Meta-analysis
ID Breast cancer; CAT; Genetic polymorphism; Meta-analysis
AB Catalase (CAT) activity is likely to be affected by functional polymorphism of C-262 T (rs1001179) in the CAT gene (OMIM: 115500). It is hypothesized that individuals with the lower expressing forms of the CAT polymorphism may be more susceptible to breast cancer. Therefore, the present case–control study and meta-analysis were carried out. The present case–control study consisted of 407 females with breast cancer and a total of 395 healthy female from population matched with patients according to age. Genotypic analysis for the CAT C-262 T polymorphism was determined by PCR. We identified 7 eligible studies, including 10,471 subjects (4,959 patients, and 5,512 healthy controls) in relation to the CAT C-262 T polymorphism and breast cancer risk. Based on the present case–control study, the CT (OR=0.90, 95 % CI: 0.66–1.22, P=0.484) and TT (OR=0.68, 95 % CI: 0.35–1.30, P=0.245) genotypes were not associated with breast cancer risk compared to the CC genotype. For metaanalysis including all studies, there was significant heterogeneity between studies. The overall ORs of the breast cancer risk were not associatedwith the CT (Q-statistic=14.90, df=6, P<0.05; OR=1.01, 95 % CI: 0.92–1.09, P=0.862) and TT (Q-statistic=2.57, df=6, P>0.05; OR=1.03, 95 % CI: 0.85– 1.24, P=0.770) genotypes. There was no association between C-262 T polymorphism of the CAT and risk of breast cancer.
C1 [Saadat, Mostafa] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
[Saadat, Shekoofeh] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
RP Saadat, M (reprint author), Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
EM saadat@shirazu.ac.ir;msaadat41@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 433
EP 437
DI 10.1007/s12253-014-9840-4
PG 5
ER
PT J
AU Kusters-Vandevelde, VNH
van Engen- van Grunsven, ACHI
Coupland, ES
Lake, LS
Rijntjes, J
Pfundt, R
Kusters, B
Wesseling, P
Blokx, AMW
Groenen, JTAP
AF Kusters-Vandevelde, V N Heidi
van Engen- van Grunsven, A C H Ilse
Coupland, E Sarah
Lake, L Sarah
Rijntjes, Jos
Pfundt, Rolph
Kusters, Benno
Wesseling, Pieter
Blokx, A M Willeke
Groenen, J T A Patricia
TI Mutations in G Protein Encoding Genes and Chromosomal Alterations in Primary Leptomeningeal Melanocytic Neoplasms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Leptomeningeal melanocytic neoplasm; Melanocytoma; Melanoma; Central nervous system; GNAQ; GNA11
ID Leptomeningeal melanocytic neoplasm; Melanocytoma; Melanoma; Central nervous system; GNAQ; GNA11
AB Limited data is available on the genetic features of primary leptomeningeal melanocytic neoplasms (LMNs). Similarities with uveal melanoma were recently suggested as both entities harbor oncogenic mutations in GNAQ and GNA11. Whether primary LMNs share additional genetic alterations with uveal melanoma including copy number variations is unknown. Twenty primary LMNs ranging from benign and intermediate-grade melanocytomas to melanomas were tested by direct sequencing for hotspot mutations in the genes GNA11, GNAQ, BRAF, NRAS and HRAS. Furthermore, the lesions were tested for copy number variations of chromosomes frequently present in uveal melanoma (1p, 3, 6 and 8q) by multiplex ligation-dependent probe amplification (MLPA). Genome-wide analyses of copy number alterations of two leptomeningeal melanocytic neoplasms were performed using the OncoScan SNP-array. GNAQQ209 mutations were present in eleven LMNs, while two of 20 cases carried a GNA11Q209 mutation. No BRAF, HRAS or NRAS hotspot mutations were detected. Monosomy 3 and gain of 8q were present in one leptomeningeal melanoma, and one intermediate-grade melanocytoma harbored a gain of chromosome 6. With MLPA, the melanocytomas did not show any further gross chromosomal variations. Our data shows that primary LMNs, like uveal melanoma, harbor oncogenic mutations in GNAQ and GNA11 but lack mutations in BRAF, NRAS and HRAS. This finding may help in the differential diagnosis between a primary LMN and a metastasis from a cutaneous melanoma to the central nervous system. Copy number variations in some aggressive LMNs resemble those present in uveal melanoma but their prognostic significance is unclear.
C1 [Kusters-Vandevelde, V N Heidi] Canisius Wilhelmina Hospital, Department of Pathology, C66, 6500 GS Nijmegen, The Netherlands.
[van Engen- van Grunsven, A C H Ilse] Radboud University Nijmegen, Medical Centre, Department of Pathology, 6500 HB Nijmegen, The Netherlands.
[Coupland, E Sarah] University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Pathology, Daulby Street, L69 3GA Liverpool, UK.
[Lake, L Sarah] University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Pathology, Daulby Street, L69 3GA Liverpool, UK.
[Rijntjes, Jos] Radboud University Nijmegen, Medical Centre, Department of Pathology, 6500 HB Nijmegen, The Netherlands.
[Pfundt, Rolph] Radboud University Medical Center, Department of Human Genetics, 6500 HB Nijmegen, The Netherlands.
[Kusters, Benno] Radboud University Nijmegen, Medical Centre, Department of Pathology, 6500 HB Nijmegen, The Netherlands.
[Wesseling, Pieter] Canisius Wilhelmina Hospital, Department of Pathology, C66, 6500 GS Nijmegen, The Netherlands.
[Blokx, A M Willeke] Radboud University Nijmegen, Medical Centre, Department of Pathology, 6500 HB Nijmegen, The Netherlands.
[Groenen, J T A Patricia] Radboud University Nijmegen, Medical Centre, Department of Pathology, 6500 HB Nijmegen, The Netherlands.
RP Kusters-Vandevelde, VNH (reprint author), Canisius Wilhelmina Hospital, Department of Pathology, C66, 6500 GS Nijmegen, The Netherlands.
EM h.kusters@cwz.nl
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Wang H, Zhang S,Wu C, Zhang Z, Qin T, 2013)Melanocytomas of the central nervous system: a clinicopathological and molecular study. Eur J Clin Invest 43:809–15
PedersenM,Kusters-VandeveldeHV, VirosA,Groenen PJ, Sanchez- Laorden B, Gilhuis JH, van Engen-van Grunsven IA, Renier W, Schieving J, Niculescu-Duvaz I, Springer CJ, Kusters B, Wesseling P, Blokx WA, Marais R, 2013, Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes. Cancer Discov 3:458–469
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 439
EP 447
DI 10.1007/s12253-014-9841-3
PG 9
ER
PT J
AU Dehghan, R
Hosseinpour Feizi, AM
Pouladi, N
Babaei, E
Montazeri, V
Fakhrjoo, A
Sedaei, A
Azarfam, P
Nemati, M
AF Dehghan, Roghayeh
Hosseinpour Feizi, Ali Mohammad
Pouladi, Nasser
Babaei, Esmaeil
Montazeri, Vahid
Fakhrjoo, Ashraf
Sedaei, Ayda
Azarfam, Parvin
Nemati, Masoumeh
TI Association of P53 (−16ins-Pro) Haplotype with the Decreased Risk of Differentiated Thyroid Carcinoma in Iranian-Azeri Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid; Neoplasms; P53 tumor suppressor protein; Polymorphism; Haplotype; Molecular marker
ID Thyroid; Neoplasms; P53 tumor suppressor protein; Polymorphism; Haplotype; Molecular marker
AB Association of P53 polymorphisms with the increased risk of various cancers has been investigated in numerous studies. However, the results were conflicting and no polymorphism has been determined as a definite risk factor. It is likely that the study of P53 combined genotypes and haplotypes may be more useful than individual polymorphisms. Thus, in this study, we analyzed the associations of intron 3 Ins16bp and exon 4 Arg72Pro polymorphisms, aswell as their combined genotypes and haplotypes with the risk of differentiated thyroid carcinoma in Iranian-Azeri patients. This case– control study was performed on 84 Iranian Azeri patients with differentiated thyroid carcinoma and 150 healthy subjects. Intron 3 genotype was determined using PCR products analysis on polyacrylamide gels and AS-PCR was used for genotyping Arg72Pro polymorphism. The javastat online statistics package software and SHEsis program were applied for data analysis. There was no significant difference in genotype frequencies of both two polymorphisms between cases and controls. However, the (−16ins/−16ins) (Arg/Pro) genotype combination had a noticeable but not significant association with decreased risk of thyroid cancer development (OR= 0.497 95%CI: 0.209–1.168 P=0.080) and also the frequency of (−16ins-Pro) haplotype was significantly higher in controls rather than patients (OR=0.543 95%CI: 0.326–0.903 P=0.018). In our study, there was association between (−16ins-Pro) haplotype with decreased risk of differentiated thyroid carcinoma development in Iranian-Azeri patients.
C1 [Dehghan, Roghayeh] Tabriz University, Department of BiologyTabriz, Iran.
[Hosseinpour Feizi, Ali Mohammad] Tabriz University, Department of BiologyTabriz, Iran.
[Pouladi, Nasser] Azarbaijan Shahid Madani University, Department of BiologyTabriz, Iran.
[Babaei, Esmaeil] Tabriz University, Department of BiologyTabriz, Iran.
[Montazeri, Vahid] Noor-E-Nejat Hospital, Department of Thorax SurgeryTabriz, Iran.
[Fakhrjoo, Ashraf] Tabriz University of Medical Sciences, Department of PathologyTabriz, Iran.
[Sedaei, Ayda] Tabriz University, Department of BiologyTabriz, Iran.
[Azarfam, Parvin] Tabriz University, Department of BiologyTabriz, Iran.
[Nemati, Masoumeh] Tabriz University, Department of BiologyTabriz, Iran.
RP Hosseinpour Feizi, AM (reprint author), Tabriz University, Department of Biology, Tabriz, Iran.
EM pourfeiz@eastp.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 449
EP 454
DI 10.1007/s12253-014-9846-y
PG 6
ER
PT J
AU Pan, W
Li, G
Yang, X
Miao, J
AF Pan, Weiran
Li, Gang
Yang, Xiaoxiao
Miao, Jinming
TI Revealing the Potential Pathogenesis of Glioma by Utilizing a Glioma Associated Protein-Protein Interaction Network
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Differentially expressed genes; Glioma associated protein-protein interaction network; Functional enrichment analysis
ID Glioma; Differentially expressed genes; Glioma associated protein-protein interaction network; Functional enrichment analysis
AB This study aims to explore the potential mechanism of glioma through bioinformatic approaches. The gene expression profile (GSE4290) of glioma tumor and non-tumor samples was downloaded from Gene Expression Omnibus database. A total of 180 samples were available, including 23 non-tumor and 157 tumor samples. Then the raw data were preprocessed using robust multiarray analysis, and 8,890 differentially expressed genes (DEGs) were identified by using ttest (false discovery rate<0.0005). Furthermore, 16 known glioma related genes were abstracted from Genetic Association Database. After mapping 8,890 DEGs and 16 known glioma related genes to Human Protein Reference Database, a glioma associated protein-protein interaction network (GAPN) was constructed. In addition, 51 sub-networks in GAPN were screened out through Molecular Complex Detection (score≥1), and sub-network 1 was found to have the closest interaction (score=3). What’ more, for the top 10 sub-networks, Gene Ontology (GO) enrichment analysis (p value<0.05) was performed, and DEGs involved in subnetwork 1 and 2, such as BRMS1L and CCNA1, were predicted to regulate cell growth, cell cycle, and DNA replication via interacting with known glioma related genes. Finally, the overlaps of DEGs and human essential, housekeeping, tissue-specific genes were calculated (p value=1.0, 1.0, and 0.00014, respectively) and visualized by Venn Diagram package in R. About 61 % of human tissue-specific genes were DEGs as well. This research shed new light on the pathogenesis of glioma based on DEGs and GAPN, and our findings might provide potential targets for clinical glioma treatment.
C1 [Pan, Weiran] Shengjing Hospital of China Medical University, Department of Neurosurgery, NO. 36 Sanhaojie Street, Heping District, 110004 Shenyang, China.
[Li, Gang] Shengjing Hospital of China Medical University, Department of Neurosurgery, NO. 36 Sanhaojie Street, Heping District, 110004 Shenyang, China.
[Yang, Xiaoxiao] Shengjing Hospital of China Medical University, Department of Neurosurgery, NO. 36 Sanhaojie Street, Heping District, 110004 Shenyang, China.
[Miao, Jinming] Shengjing Hospital of China Medical University, Department of Neurosurgery, NO. 36 Sanhaojie Street, Heping District, 110004 Shenyang, China.
RP Pan, W (reprint author), Shengjing Hospital of China Medical University, Department of Neurosurgery, 110004 Shenyang, China.
EM weiranpan2@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 455
EP 462
DI 10.1007/s12253-014-9848-9
PG 8
ER
PT J
AU Forghanifard, MM
Taleb, Sh
Abbaszadegan, RM
AF Forghanifard, Mahdi Mohammad
Taleb, Shaghayegh
Abbaszadegan, Reza Mohammad
TI Notch Signaling Target Genes are Directly Correlated to Esophageal Squamous Cell Carcinoma Tumorigenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Notch signaling pathway; Esophageal squamous cell carcinoma; Real time PCR; HEY1; HEY2
ID Notch signaling pathway; Esophageal squamous cell carcinoma; Real time PCR; HEY1; HEY2
AB Notch signaling is an important cellular pathway which affects the development and function ofmany organs. It plays critical roles in maintaining of progenitor stem cell population as well as balancing cell proliferation, survival, differentiation and apoptosis. It has been shown that notch signaling is aberrantly activated during the carcinogenesis of a variety of human cancers. In this study we aimed to explore activation of this signaling pathway in esophageal squamous cell carcinoma (ESCC) through expressional analysis of notch signaling target genes. The mRNA expression of HEY1and HEY2 was comparatively analyzed by real-time PCR in tumor and related margin normal tissues of 50 ESCC patients. Comparative quantitative real-time PCR indicates the overexpression of HEY1 and HEY2 in 54 and 30 % of ESCC samples, respectively. Overexpression of HEY1 was significantly associated with stage of the tumor (p=0.048) and tumor location (p=0.008). HEY2 overexpression was also significantly correlated to node metastasis of tumor cells (p=0.043). Overexpression of HEY1 and HEY2 in ESCC is correlated to different indices of poor prognosis and it is extrapolated that such overexpression is important in progression and development of ESCC tumorigenesis. To the best of our knowledge, this is the first report introducing aberrant activation of notch signaling target genes in ESCC, where it plays roles in development and progression of the malignancy and may be considered in therapeutic modalities to restrict ESCC progression.
C1 [Forghanifard, Mahdi Mohammad] Islamic Azad University, Damghan Branch, Department of Biology, Cheshmeh-Ali Boulevard, Sa’dei Square, 3671639998 Damghan, Iran.
[Taleb, Shaghayegh] Mashhad University of Medical Sciences, Medical School, Medical Genetics Research CenterMashhad, Iran.
[Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, Bu-Ali square, 9196773117 Mashhad, Iran.
RP Abbaszadegan, RM (reprint author), Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
EM Abbaszadeganmr@mums.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 463
EP 467
DI 10.1007/s12253-014-9849-8
PG 5
ER
PT J
AU Yuan, P
Liu, D
Deng, M
Liu, J
Wang, J
Zhang, L
Liu, Q
Zhang, T
Chen, Y
Jin, G
AF Yuan, Pengfei
Liu, Dechun
Deng, Miao
Liu, Jiangbo
Wang, Jianguang
Zhang, Like
Liu, Qipeng
Zhang, Ting
Chen, Yanbin
Jin, Gaoyuan
TI Identification of Differently Expressed Genes with Specific SNP Loci for Breast Cancer by the Integration of SNP and Gene Expression Profiling Analyses
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Single nucleotide polymorphisms; Gene expression profile; Fisher’s combined probability test; Correlation analysis; Transcription factor
ID Breast cancer; Single nucleotide polymorphisms; Gene expression profile; Fisher’s combined probability test; Correlation analysis; Transcription factor
AB This study aims to explore the relationship between gene polymorphism and breast cancer, and to screen DEGs (differentially expressed genes) with SNPs (single nucleotide polymorphisms) related to breast cancer. The SNPs of 17 patients and the preprocessed SNP profiling GSE 32258 (38 cases of normal breast cells) were combined to identify their correlation with breast cancer using chi-square test. The gene expression profiling batch8_9 (38 cases of patients and 8 cases of normal tissue) was preprocessed with limma package, and the DEGs were filtered out. Then fisher’s method was applied to integrate DEGs and SNPs associated with breast cancer. With NetBox software, TRED (Transcriptional Regulatory Element Database) and UCSC (University of California Santa Cruz) database, genes-associated network and transcriptional regulatory network were constructed using cytoscape software. Further, GO (Gene Ontology) and KEGG analyses were performed for genes in the networks by using siggenes. In total, 332 DEGs were identified. There were 160 breast cancer-related SNPs related to 106 genes of gene expression profiling (19 were significant DEGs). Finally, 11co-correlated DEGs were selected. In genes-associated network, 9 significant DEGs were correlated to 23 LINKER genes while, in transcriptional regulatory network, E2F1 had regulatory relationships with 7 DEGs including MTUS1, CD44, CCNB1 and CCND2. KRAS with SNP locus of rs1137282 was involved in 35 KEGG pathways. The genes of MTUS1, CD44, CCNB1, CCND2 and KRAS with specific SNP loci may be used as biomarkers for diagnosis of breast cancer. Besides, E2F1 was recognized as the transcription factor of 7 DEGs including MTUS1, CD44, CCNB1 and CCND2.
C1 [Yuan, Pengfei] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Liu, Dechun] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Deng, Miao] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Liu, Jiangbo] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Wang, Jianguang] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Zhang, Like] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Liu, Qipeng] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Zhang, Ting] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Chen, Yanbin] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
[Jin, Gaoyuan] The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, Jinghua Road No. 24, Jianxi District, 471003 Luoyang, China.
RP Liu, D (reprint author), The First Affiliated Hospital of Henan University Science and Technology, Department of Breast Surgery, 471003 Luoyang, China.
EM liudechun2008@126.com
CR Sariego J, 2010, Breast cancer in the young patient. Am Surg 76(12): 1397–1400
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 469
EP 475
DI 10.1007/s12253-014-9851-1
PG 7
ER
PT J
AU Bianchi, S
Caini, S
Paglierani, M
Saieva, C
Vezzosi, V
Baroni, G
Simoni, A
Palli, D
AF Bianchi, Simonetta
Caini, Saverio
Paglierani, Milena
Saieva, Calogero
Vezzosi, Vania
Baroni, Gianna
Simoni, Antonella
Palli, Domenico
TI Accuracy and Reproducibility of HER2 Status in Breast Cancer Using Immunohistochemistry: A Quality Control Study in Tuscany Evaluating the Impact of Updated 2013 ASCO/CAP Recommendations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Human epidermal growth factor receptor 2; Immunohistochemistry; Fluorescence in situ hybridization; Accuracy; Reproducibility
ID Breast cancer; Human epidermal growth factor receptor 2; Immunohistochemistry; Fluorescence in situ hybridization; Accuracy; Reproducibility
AB The correct identification of HER2-positive cases is a key point to provide the most appropriate therapy to breast cancer (BC) patients.We aimed at investigating the reproducibility and accuracy of HER2 expression by immunohistochemistry (IHC) in a selected series of 35 invasive BC cases across the pathological anatomy laboratories in Tuscany, Italy. Unstained sections of each BC case were sent to 12 participating laboratories. Pathologists were required to score according to the Food and Drug Administration (FDA) four-tier scoring system (0, 1+, 2+, 3+). Sixteen and nineteen cases were HER2 non-amplified and amplified respectively on fluorescence in situ hybridization. Among 192 readings of the 16 HER2 non-amplified samples, 153 (79.7 %) were coded as 0 or 1+, 39 (20.3 %) were 2+, and none was 3+ (false positive rate 0 %). Among 228 readings of the 19 HER2 amplified samples, 56 (24.6 %) were scored 0 or 1+, 79 (34.6 %) were 2+, and 93 (40.8 %) were 3+. The average sensitivity was 75.4 %, ranging between 47 % and 100 %, and the overall false negative rate was 24.6 %. Participation of pathological anatomy laboratories performing HER2 testing by IHC in external quality assurance programs should be made mandatory, as the system is able to identify laboratories with suboptimal performance that may need technical advice. Updated 2013 ASCO/CAP recommendations should be adopted as the widening of IHC 2+ "equivocal" category would improve overall accuracy of HER2 testing, as more cases would be classified in this category and, consequently, tested with an in situ hybridisation method.
C1 [Bianchi, Simonetta] AOU Careggi, Department of Surgery and Translational MedicineFlorence, Italy.
[Caini, Saverio] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
[Paglierani, Milena] AOU Careggi, Department of Surgery and Translational MedicineFlorence, Italy.
[Saieva, Calogero] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
[Vezzosi, Vania] AOU Careggi, Department of Surgery and Translational MedicineFlorence, Italy.
[Baroni, Gianna] AOU Careggi, Department of Surgery and Translational MedicineFlorence, Italy.
[Simoni, Antonella] AOU Careggi, Department of Surgery and Translational MedicineFlorence, Italy.
[Palli, Domenico] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
RP Bianchi, S (reprint author), AOU Careggi, Department of Surgery and Translational Medicine, Florence, Italy.
EM simonetta.bianchi@unifi.it
CR Popescu NC, King CR, Kraus MH, 1989, Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12-21.32. Genomics 4:362–366
Perez EA, Cortes J, Gonzalez-Angulo AM, JMS et al, 2014, HER2 testing: current status and future directions. Cancer Treat Rev 40: 276–284
Hanna WM, Ruschoff J, Bilous M et al, 2014, HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol 27:4–18
Wolff AC, Hammond EH, Schwartz JN et al, 2007, American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145
Provenzano E, Johnson N, 2009, Overview of recommendations of HER2 testing in breast cancer. Diagn Histopathol 15:478–484
Walker RA, Bartlett JM, DowsettMet al, 2008)HER2 testing inUK: further update to recommendations. J Clin Pathol 61:818–824
Wolff AC, Hammond EH, Hicks DG et al, 2013, Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31: 3997–4013
Hanna W, O’Malley FP, Barnes P et al, 2007, Updated recommendations from the Canadian National Consensus Meeting on HER2/neu testing in breast cancer. Curr Oncol 4:149–153
Paik S, Bryant J, Tan-Chiu E et al, 2002, Real-world performance of HER2 testing-National Surgical adjuvant Breast and Bowel Project Experience. J Natl Cancer Inst 94:852–854
Vogel CL, Bloom K, Burris H et al, 2011, Discordance between central and local laboratory Her2 testing from a large HER2-negative population in VIRGO, a metastatic breast cancer registry. Cancer Res 71(24):188s
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Schrohl AS, Pedersen HC, Jonsen SS et al, 2011, Human epidermal growth factors receptors 2, HER2, immunoreactivity: specificity of three pharmacodiagnostic antibodies. Histopathology 59: 975–983
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Sauter G, Lee J, Bartlett JMS et al, 2009, Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 27:1323–1333
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 477
EP 485
DI 10.1007/s12253-014-9852-0
PG 9
ER
PT J
AU Togami, Sh
Sasajima, Y
Kasamatsu, T
Oda-Otomo, R
Okada, S
Ishikawa, M
Ikeda, Shi
Kato, T
Tsuda, H
AF Togami, Shinichi
Sasajima, Yuko
Kasamatsu, Takahiro
Oda-Otomo, Rie
Okada, Satoshi
Ishikawa, Mitsuya
Ikeda, Shun-ichi
Kato, Tomoyasu
Tsuda, Hitoshi
TI Immunophenotype and Human Papillomavirus Status of Serous Adenocarcinoma of the Uterine Cervix
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serous adenocarcinoma; Uterine cervix; Immunohistochemical features; Human papillomavirus
ID Serous adenocarcinoma; Uterine cervix; Immunohistochemical features; Human papillomavirus
AB Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n=12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0 %, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50 %, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p<0.01).HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.
C1 [Togami, Shinichi] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Sasajima, Yuko] National Cancer Center Hospital, Department of Pathology and Clinical Laboratories, Chuo-kuTokyo, Japan.
[Kasamatsu, Takahiro] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Oda-Otomo, Rie] National Cancer Center Hospital, Department of Pathology and Clinical Laboratories, Chuo-kuTokyo, Japan.
[Okada, Satoshi] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Ishikawa, Mitsuya] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Ikeda, Shun-ichi] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Kato, Tomoyasu] National Cancer Center Hospital, Department of Gynecology, 5-1–1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.
[Tsuda, Hitoshi] National Cancer Center Hospital, Department of Pathology and Clinical Laboratories, Chuo-kuTokyo, Japan.
RP Togami, Sh (reprint author), National Cancer Center Hospital, Department of Gynecology, 104-0045 Tokyo, Japan.
EM togami@m3.kufm.kagoshima-u.ac.jp
CR Olawaiye AB, Rauh-Hain JA, Withiam-Leitch M, Rueda B, Goodman A, del Carmen MG, 2008, Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma. Gynecol Oncol 110(3):293–298
Zhou C, Gilks CB, Hayes M, Clement PB, 1998, Papillary serous carcinoma of the uterine cervix: a clinicopathologic study of 17 cases. Am J Surg Pathol 22(1):113–120
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Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, 2007, American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131(1):18–43
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Baalbergen A, Ewing-Graham PC, Eijkemans MJ, Helmerhorst TJ, 2007, Prognosis of adenocarcinoma of the uterine cervix: p53 expression correlates with higher incidence of mortality. Int J Cancer 121(1):106–110
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Batistatou A, Zolota V, Tzoracoleftherakis E, Scopa CD, 2000, Papillary serous adenocarcinoma of the endocervix: a rare neoplasm. Immunohistochemical profile. Int J Gynecol Cancer 10(4):336–339
Nofech-Mozes S, Rasty G, Ismiil N, Covens A, Khalifa MA, 2006, Immunohistochemical characterization of endocervical papillary serous carcinoma. Int J Gynecol Cancer 16(Suppl 1):286–292
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Fontaine J, Hankins C, Mayrand MH, Lefevre J, Money D, Gagnon S, Rachlis A, Pourreaux K, Ferenczy A, Coutlee F, 2005, High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV. AIDS, London, England, 19(8): 785–794
Riethdorf L, Riethdorf S, Lee KR, Cviko A, Loning T, Crum CP, 2002, Human papillomaviruses, expression of p16, and early endocervical glandular neoplasia. Hum Pathol 33(9):899–904
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Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S, 2003, Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 88(1):63–73
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Nofech-Mozes S, Khalifa MM, Ismiil N, Dube V, Saad RS, Sun P, Seth A, 2010, Ghorab Z Detection of HPV-DNA by a PCR-based method in formalin-fixed, paraffin-embedded tissue from rare endocervical carcinoma types. Appl Immunohistochem Mol Morphol 18(1):80–85
Hadzisejdc I, Krasevic M, Haller H, Grahovac B, 2007, Distribution of human papillomavirus types in different histological subtypes of cervical adenocarcinoma. Coll Anthropol 31(Suppl 2):97–102
Acs G, Pasha T, Zhang PJ, 2004, WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium. Int J Gynecol Pathol 23(2):110–118
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Hylander B, Repasky E, Shrikant P, IntenganM, Beck A, Driscoll D, Singhal P, Lele S, Odunsi K, 2006, Expression ofWilms tumor gene, WT1, in epithelial ovarian cancer. Gynecol Oncol 101(1):12–17
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Nofech-Mozes S, Khalifa MA, Ismiil N, Saad RS, Hanna WM, Covens A, Ghorab Z, 2008, Immunophenotyping of serous carcinoma of the female genital tract. Mod Pathol 21(9):1147–1155 2 9. De a v e r s MT, M a l p i c a A, S i l v a EG, 2 0 0 3 , Immunohistochemistry in gynecological pathology. Int J Gynecol Cancer 13(5):567–579 30. Alkushi A, Irving J, Hsu F, Dupuis B, Liu CL, Rijn M, Gilks CB, 2003, Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Arch 442(3):271–277 31. Santin AD, Bellone S, Van Stedum S, BushenW, PalmieriM, Siegel ER, De Las Casas LE, Roman JJ, Burnett A, Pecorelli S, 2005, Amplification of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma. Cancer 104(7):1391–1397 32. Slomovitz BM, Broaddus RR, Burke TW, Sneige N, Soliman PT,Wu W, Sun CC, MunsellMF, Gershenson DM, Lu KH, 2004, Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. J Clin Oncol 22(15):3126–3132 33. Togami S, Sasajima Y, Oi T, Ishikawa M, Onda T, Ikeda S, Kato T, Tsuda H, Kasamatsu T, 2012, Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2, HER2, and hormone receptor expression in uterine papillary serous carcinoma. Cancer Sci 103(5):926–932
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 487
EP 494
DI 10.1007/s12253-014-9854-y
PG 8
ER
PT J
AU Nemeth, H
Kuronya, Zs
Biro, K
Kormosoi-Toth, K
Horvath, Sz
Geczi, L
AF Nemeth, Hajnalka
Kuronya, Zsofia
Biro, Krisztina
Kormosoi-Toth, Krisztina
Horvath, Szabolcs
Geczi, Lajos
TI Pericardial Tamponade Caused by Tumor Hemorrhage – a Rare Complication of Metastatic Testicular Choriocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Nemeth, Hajnalka] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Kuronya, Zsofia] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Biro, Krisztina] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Kormosoi-Toth, Krisztina] National Institute of Oncology, Department of Anesthesiology and Intensive TherapyBudapest, Hungary.
[Horvath, Szabolcs] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Geczi, Lajos] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
RP Nemeth, H (reprint author), National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Budapest, Hungary.
EM nemethhajnalka@hotmail.com
CR Williams MB, Schwartz BF, 2012, Testicular choriocarcinoma. http://emedicine.medscape.com/article/435577-overview . Accessed 26 Dec 2013
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 495
EP 499
DI 10.1007/s12253-014-9842-2
PG 5
ER
PT J
AU Choudhari, KSh
Gadbail, RA
AF Choudhari, Korde Sheetal
Gadbail, R Amol
TI Hybrid Odontogenic Tumors: A Controversy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choudhari, Korde Sheetal] Yerala Dental College and Hospital, Department of Oral Pathology & Microbiology, B-15, Mandovi, Chheda Nagar, Chembur(W), 4400089 Mumbai, Maharashtra, India.
[Gadbail, R Amol] Sharad Pawar Dental College, Department of Oral Pathology & Microbiology, Sawangi, 442001 Wardha, Maharashatra, India.
RP Choudhari, KSh (reprint author), Yerala Dental College and Hospital, Department of Oral Pathology & Microbiology, 4400089 Mumbai, India.
EM kordesheetal@yahoo.co.in
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2015
VL 21
IS 2
BP 501
EP 502
DI 10.1007/s12253-014-9844-0
PG 2
ER
PT J
AU Galamb,
Benczik, M
Zinner, B
Vigh, E
Baghy, K
Jeney, Cs
Kiss, A
Lendvai, G
Sobel, G
AF Galamb, Adam
Benczik, Marta
Zinner, Balazs
Vigh, Eszter
Baghy, Kornelia
Jeney, Csaba
Kiss, Andras
Lendvai, Gabor
Sobel, Gabor
TI Dysregulation of microRNA Expression in Human Cervical Preneoplastic and Neoplastic Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cervix; Cervical cancer; microRNA; Biomarker; Screening
ID Cervix; Cervical cancer; microRNA; Biomarker; Screening
AB Data discussed in recent reviews demonstrated that dysregulation of microRNA (miRNA) expression profiles occurs during cervical carcinogenesis and characteristic upor downregulation of certain miRNAs might be used as biomarkers. The majority of altered miRNAs, however were found to be inconsistent upon comparison with cancerous and normal cervical epithelia in the discussed studies due to several reasons. The results obtained in this present review suggest the need for further investigations on miRNAs on larger sample sizes in order to indicate sensitivity and specificity by means of well defined, "unified" methods. In addition, obtaining further data on the clinical course and outcome of patients in comparison to the dysregulation of miRNA expression profile could turn miRNAs into prognostic and/or progression markers. Inhibition of overexpressed miRNAs, as suggested by some authors, might even serve as target for cancer therapy.
C1 [Galamb, Adam] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
[Benczik, Marta] CellCall Ltd, Roppentyu u. 48, 1134 Budapest, Hungary.
[Zinner, Balazs] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
[Vigh, Eszter] Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Jeney, Csaba] CellCall Ltd, Roppentyu u. 48, 1134 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
[Lendvai, Gabor] Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
[Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
RP Sobel, G (reprint author), Semmelweis University, 2nd Department of Obstetrics and Gynecology, 1082 Budapest, Hungary.
EM sobelg@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 503
EP 508
DI 10.1007/s12253-014-9871-x
PG 6
ER
PT J
AU Bal, MM
Ramadwar, M
Deodhar, K
Shrikhande, Sh
AF Bal, Meenu Munita
Ramadwar, Mukta
Deodhar, Kedar
Shrikhande, Shailesh
TI Pathology of Gallbladder Carcinoma: Current Understanding and New Perspectives
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Gallbladder carcinoma; Epidemiology; Pathways; Terminology; Precancerous lesions; Histologic subtypes; Molecular pathology
ID Gallbladder carcinoma; Epidemiology; Pathways; Terminology; Precancerous lesions; Histologic subtypes; Molecular pathology
AB Gallbladder carcinoma is a rare and highly lethal malignancy. It stands out from amongst the other GI tract malignancies for its unique epidemiological profile, proclivity for female gender, definitional ambiguities, ability to escape early diagnosis, and absence of effective treatment. Pathobiology of gallbladder carcinoma continues to remain poorly understood. Recently, better characterization of the precursor lesions and elucidation of underlying molecular pathways has enhanced our understanding of gallbladder tumorigenesis. Proposal of a unified terminology and evolving consensus in classifying gallbladder pre-invasive neoplasia offers hope of better assimilation of rare data from diverse parts of the world. Identifying biomarkers and cancer specific cellular targets that will pave the way for novel therapeutic approaches for gallbladder carcinoma is urgently needed. In this review we delve into the epidemiologic, genetic and pathologic characteristics of this enigmatic disease with a special focus on the recent advancements in the field of gallbladder pathology.
C1 [Bal, Meenu Munita] Tata Memorial Hospital, Department of Pathology, 400012 Parel, Mumbai, India.
[Ramadwar, Mukta] Tata Memorial Hospital, Department of Pathology, 400012 Parel, Mumbai, India.
[Deodhar, Kedar] Tata Memorial Hospital, Department of Pathology, 400012 Parel, Mumbai, India.
[Shrikhande, Shailesh] Tata Memorial Hospital, Department of Hepato-Pancreato-Biliary Surgical Oncology, 400012 Parel, Mumbai, India.
RP Bal, MM (reprint author), Tata Memorial Hospital, Department of Pathology, 400012 Parel, India.
EM munitamenon@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 509
EP 525
DI 10.1007/s12253-014-9886-3
PG 17
ER
PT J
AU Fernandes, VJ
Cobucci, NOR
Jatoba, ANC
de Medeiros Fernandes, AATh
de Azevedo, WVJ
de Araujo, MGJ
AF Fernandes, Verissimo Jose
Cobucci, Ney Oliveira Ricardo
Jatoba, Andre Nunes Carlos
de Medeiros Fernandes, Allyrio Araujo Thales
de Azevedo, Welber Verissimo Judson
de Araujo, Maria Galvao Joselio
TI The Role of the Mediators of Inflammation in Cancer Development
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Inflammation and cancer; Inflammation mediators; Mechanisms of tumorigenesis
ID Inflammation and cancer; Inflammation mediators; Mechanisms of tumorigenesis
AB Epigenetic disorders such as point mutations in cellular tumor suppressor genes, DNA methylation and posttranslational modifications are needed to transformation of normal cells into cancer cells. These events result in alterations in critical pathways responsible for maintaining the normal cellular homeostasis, triggering to an inflammatory response which can lead the development of cancer. The inflammatory response is a universal defense mechanism activated in response to an injury tissue, of any nature, that involves both innate and adaptive immune responses, through the collective action of a variety of soluble mediators. Many inflammatory signaling pathways are activated in several types of cancer, linking chronic inflammation to tumorigenesis process. Thus, Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, growth, invasion, and metastasis, affecting also the immune surveillance. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. A range of inflammation mediators, including cytokines, chemokines, free radicals, prostaglandins, growth and transcription factors, microRNAs, and enzymes as, cyclooxygenase and matrix metalloproteinase, collectively acts to create a favorable microenvironment for the development of tumors. In this review are presented the main mediators of the inflammatory response and discussed the likely mechanisms through which, they interact with each other to create a condition favorable to development of cancer.
C1 [Fernandes, Verissimo Jose] Federal University of Rio Grande do Norte, Post-Graduate Program in Biological SciencesNatal, RN, Brazil.
[Cobucci, Ney Oliveira Ricardo] Federal University of Rio Grande do Norte, Maternidade Escola Januario CiccoNatal, RN, Brazil.
[Jatoba, Andre Nunes Carlos] Federal University of Rio Grande do Norte, Department of PathologyNatal, RN, Brazil.
[de Medeiros Fernandes, Allyrio Araujo Thales] University of Rio Grande do Norte State, Department of Biomedical SciencesMossoro, RN, Brazil.
[de Azevedo, Welber Verissimo Judson] Federal University of Triangulo Mineiro, Hospital UniversitarioMina Gerais, Brazil.
[de Araujo, Maria Galvao Joselio] Federal University of Rio Grande do Norte, Post-Graduate Program in Biological SciencesNatal, RN, Brazil.
RP Fernandes, VJ (reprint author), Federal University of Rio Grande do Norte, Post-Graduate Program in Biological Sciences, Natal, Brazil.
EM joseverissimo1951@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 527
EP 534
DI 10.1007/s12253-015-9913-z
PG 8
ER
PT J
AU Bianchi, S
Bendinelli, B
Saladino, V
Vezzosi, V
Brancato, B
Nori, J
Palli, D
AF Bianchi, Simonetta
Bendinelli, Benedetta
Saladino, Valeria
Vezzosi, Vania
Brancato, Beniamino
Nori, Jacopo
Palli, Domenico
TI Non-Malignant Breast Papillary Lesions - B3 Diagnosed on Ultrasound - Guided 14-Gauge Needle Core Biopsy: Analysis of 114 Cases from a Single Institution and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary lesions; 14-gauge needle core biopsy; Epithelial atypia; Excision; Associated carcinoma
ID Papillary lesions; 14-gauge needle core biopsy; Epithelial atypia; Excision; Associated carcinoma
AB One-hundred-fourteen consecutive cases of breast ultrasound-guided 14-gauge needle core biopsy (14G NCB) performed from January 2001 to June 2013 and diagnosed as non-malignant papillary lesion (PL)-B3, were reviewed and compared with definitive histological diagnosis on surgical excision (SE) to evaluate the diagnostic accuracy of ultrasound-guided 14G NCB. PL with epithelial atypia on 14G NCB were associated to malignancy on definitive histological diagnosis on SE in 22 (7 DCIS and 15 invasive carcinomas) of 46 cases with an underestimation rate of 47.8 %, while 9 (4 DCIS and 5 invasive carcinomas) cases out of 68 cases of PL without epithelial atypia were upgraded to carcinoma with an underestimation rate of 13.2 %. In cases of PL with epithelial atypia on ultrasound-guided 14G NCB, SE appears mandatory due to the high risk of associated malignancy. The diagnosis of PL without epithelial atypia on ultrasound-guided 14G NCB does not exclude malignancy at subsequent SE, consequently further assessment (by surgical or vacuum-assisted excision) is recommended to avoid the risk of delaying a diagnosis of malignancy, although this tends to be lower (1 in 8 patients).
C1 [Bianchi, Simonetta] AOU Careggi, Department of Surgery and Translational Medicine, Largo G.A. Brambilla 3, 50134 Florence, Italy.
[Bendinelli, Benedetta] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
[Saladino, Valeria] AOU Careggi, Department of Surgery and Translational Medicine, Largo G.A. Brambilla 3, 50134 Florence, Italy.
[Vezzosi, Vania] AOU Careggi, Department of Surgery and Translational Medicine, Largo G.A. Brambilla 3, 50134 Florence, Italy.
[Brancato, Beniamino] Cancer Research and Prevention Institute (ISPO), Senology UnitFlorence, Italy.
[Nori, Jacopo] Careggi University Hospital, Diagnostic Senology UnitFlorence, Italy.
[Palli, Domenico] Cancer Research and Prevention Institute (ISPO), Molecular and Nutritional Epidemiology UnitFlorence, Italy.
RP Bianchi, S (reprint author), AOU Careggi, Department of Surgery and Translational Medicine, 50134 Florence, Italy.
EM simonetta.bianchi@unifi.it
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Shin HJ, Kim HH, Kim SM, Yang HR, Sohn JH, Kwon GY et al, 2008, Papillary lesions of the breast diagnosed at percutaneous sonographically guided biopsy: comparison of sonographic features and biopsy methods. Am J Roentgenol 190:630–636
Ahmadiyeh N, Stoleru MA, Raza S, Lester SC, Golshan M, 2009, Management of intraductal papillomas of the breast: an analysis of 129 cases and their outcome. Ann Surg Oncol 16:2264–2269
Bernik SF, Troob S, Ying BL, Simpson SA, Axelord DM, Siegel B et al, 2009, Papillary lesions of the breast diagnosed by core needle biopsy: 71 cases with surgical follow-up. Am J Surg 197:473–478
BodeMK, Rissanen T, Apaja-SarkkinenM(2009, Ultrasonographyguided core needle biopsy in differential diagnosis of papillary breast tumors. Acta Radiol 7:722–729
Cheng TY, Chen CM, Lee MY, Lin KJ, Hung CF, Yang PS et al, 2009, Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary. Ann Surg Oncol 16:3375–3379
Tseng HS, Chen YL, Chen ST,Wu YC, Kuo SJ, Chen LS et al, 2009, The management of papillary lesion of the breast by core needle biopsy. J Cancer Surg 35:21–24
Bennet LE, Ghate SV, Bentley R, Baker JA, 2010, Is surgical excision of core biopsy proven benign papillomas of the breast necessary? Acad Radiol 17:553–557
Tse GM, Tan PH, LacambraMD, Jara-Lazaro AR, Chan SK, Lui PC et al, 2009, Papillary lesions of the breast accuracy of core biopsy. Histopathology 56:481–488
Youk JH, Kim EK, Kwak JY, Son EJ, Park BW, Kim SII, 2011, Benign papilloma without atypia diagnosed at us-guided 14-gauge core-needle biopsy: clinical and us features predictive of upgrade to malignancy. Radiology 258:81–88
Chang JM, HanW, MoonWK, Cho N, Noh DY, Park IA et al, 2011, Papillary lesions initially diagnosed at ultrasound-guided vacuumassisted breast biopsy: rate of malignancy based on subsequent surgical excision. Ann Surg Oncol 18:2506–2514
KimMJ,Kim SI,Youk JH, Moon HJ,Kwak JY, ParkBWet al, 2011, The diagnosis of non malignant papillary lesions of the breast: comparison of ultrasound-guided automated gun biopsy and vacuumassisted removal. Clin Radiol 66:530–535
Rakha EA, Lee AHS, Jenkins JA, Murphy AE, Hamilton LJ, Ellis IO, 2011, Characterization and outcome of breast needle core biopsy diagnoses of lesions of uncertain malignant potential, B3, in abnormalities detected by mammographic screening. Int J Cancer 129: 1417–1424
Richter-Ehrenstein C, Tombokan F, Fallenberg EM, Schneider A, Denkert C, 2011, Intraductal papillomas of the breast: diagnosis and management of 151 patients. Breast 20:501–504
Destounis S, Seifert P, Somerville P,Murphy P,Morgan R, Arieno A, Young WL, 2011, Underestimation of papillary breast lesions by core biopsy: correlation to surgical excision. Breast Cancer 18:42–50
Fu CY, Chen TW, Hong ZJ, Chan DC, Young CY, Chen CJ et al, 2012, Papillary breast lesions diagnosed by core biopsy require complete excision. EJSO 38:1029–1035
Holley SO, Appleton CM, Farria DM, Reichert VC, Warrik J, Craig Allred D et al, 2012, Patologic outcomes of nonmalignant papillary breast lesions diagnosed at imaging-guided core needle biopsy. Radiology 265:379–384
Lu Q, Tan EY, Ho B, Chen JJC, Chan PMY, 2012, Surgical excision of intraductal breast papilloma diagnosed on core biosy. ANZ J Surg 82:168–172
Rizzo M, Linebarger J, Lowe MC, Pan L, Gabram SG, Vasquez L et al, 2012, Management of papillary breast lesions diagnosed on core-needle biopsy:clinical pathologic and radiologic analysis of 276 cases with surgical follow-up. J Am Coll Surg 214:280–287
Al Hassan T, Delli Fraine P, El-Khoury M, Joseph L, Zheng J, Mesurolle B, 2013, Accuracy of percutaneous core needle biopsy in diagnosing papillary breast lesions and potential impact of sonographic features on their management. J Clin Ultrasound 41:1–9
Wiratkapun C, Keeratitragoon T, Lertsithichai P, Chanplakorn N, 2013, Upgrading rate of papillary breast lesions diagnosed by core-needle biopsy. Diagn Interv Radiol 19:361–367
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 535
EP 546
DI 10.1007/s12253-014-9882-7
PG 12
ER
PT J
AU Chen, YY
Li, FYA
Huang, KH
Lan, YT
Chen, MH
Chao, Y
Lo, SSh
Wu, ChW
Shyr, YM
Fang, WL
AF Chen, Yin-Yin
Li, Fen-Yau Anna
Huang, Kuo-Hung
Lan, Yuan-Tzu
Chen, Ming-Huang
Chao, Yee
Lo, Su-Shun
Wu, Chew-Wun
Shyr, Yi-Ming
Fang, Wen-Liang
TI Adenosquamous Carcinoma of the Stomach and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenosquamous carcinoma; Adenocarcinoma; Squamous cell carcinoma; Metastatic lymph node
ID Adenosquamous carcinoma; Adenocarcinoma; Squamous cell carcinoma; Metastatic lymph node
AB Adenosquamous carcinoma of the stomach is a very rare disease, consisting of less than 0.4 % of all stomach cancer. From 1991 to 2013, a total of 2800 patients received gastrectomy for gastric cancer at Taipei Veterans General hospital. Among them, seven patients (0.25 %) diagnosed as adenosquamous carcinoma were enrolled. The clinicopathologic characteristics and prognosis were analyzed. The mean age of the seven patients was 62.3 years-old. There were 5 males and 2 females. Six patients were stage III disease and one patient was stage IV disease. Four patients finally died of gastric cancer. Only one patient had no recurrence until death. Among the seven patients, adenocarcinoma component comprises the majority of the metastatic lymph node in 6 patients (85.7 %). The only one patient with major squamous cell carcinoma component in metastatic lymph node had no tumor recurrence till death. Adenosquamous carcinoma of stomach is a rare disease and is associated with a poor prognosis. The component of adenocarcinoma and squamous cell carcinoma in the metastatic lymph node may influence the prognosis.
C1 [Chen, Yin-Yin] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Li, Fen-Yau Anna] Taipei Veterans General Hospital, Department of PathologyTaipei, Taiwan, Republic of China.
[Huang, Kuo-Hung] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Lan, Yuan-Tzu] Taipei Veterans General Hospital, Department of Surgery, Division of Colon & Rectal SurgeryTaipei, Taiwan, Republic of China.
[Chen, Ming-Huang] Taipei Veterans General Hospital, Department of Medicine, Division of Hematology and OncologyTaipei, Taiwan, Republic of China.
[Chao, Yee] Taipei Veterans General Hospital, Department of Medicine, Division of Hematology and OncologyTaipei, Taiwan, Republic of China.
[Lo, Su-Shun] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Wu, Chew-Wun] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Shyr, Yi-Ming] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Fang, Wen-Liang] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
RP Fang, WL (reprint author), Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, 11217 Taipei, Taiwan, Republic of China.
EM s821094@hotmail.com
CR Mori E, Watanabe A, Maekawa S et al, 2000, Adenosquamous carcinoma of the remnant stomach: report of a case. Surg Today 30:643– 646
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Tohma T, Yamamoto Y, Seki Yet al, 2009)Weekly paclitaxel therapy is effective for gastric adenosquamous carcinoma: a case report. Hepatogastroenterology 56:568–570
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Sobin L, Gospodarowicz M, Wittekind C, eds,, 2009, TNM classification of malignant tumours, UICC International Union Against Cancer), 7th edn. New York, Wiley-Blackwell
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 547
EP 551
DI 10.1007/s12253-014-9890-7
PG 5
ER
PT J
AU Ben Abdelkrim, S
Fathallah, K
Rouatbi, R
Ayachi, M
Hmissa, S
Mokni, M
AF Ben Abdelkrim, Soumaya
Fathallah, Khadija
Rouatbi, Rim
Ayachi, Malak
Hmissa, Sihem
Mokni, Moncef
TI OM.Breast Cancer in Very Young Women Aged 25 Year-Old or Below in the Center of Tunisia and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Young women; Tunisia; 25 years-old
ID Breast cancer; Young women; Tunisia; 25 years-old
AB Breast cancer in very young women under 40 or 35 years attracted a widespread attention. Few studies have focused on women aged below 25 years. The aim of this study was to evaluate the situation of breast cancer in women ≤25 years in the center of Tunisia. Retrospective review from 1993 to 2013. Clinical, histopathological, therapeutic and outcome data were recorded. Cases were classified into different molecular subtypes based on the immunohistochemistrybased definitions. The series included 25 patients. The mean duration of symptoms was 7.5 months. The most common presenting symptom was a palpable mass. Four patients had at least one relative diagnosed with breast cancer. Mammography combined with ultrasound was suggestive of malignancy in 60 % of cases. Curative surgical treatment could be offered in 19 cases. The mean tumor size was 39 mm. Nodal metastases were detected in 9/18 cases. Twenty cases could be classified into: luminal A (5 cases), luminal B (6 cases), Her-2 (1 case), triple negative (6 cases) and unclassified (2 cases). Two women experienced locoregional recurrence and 6 had distant recurrence. Asynchronous contralateral breast cancer occurred in one case. The overall survival at 5 and 10 years was 85 and 75 % respectively. The survival was significantly lower in grade III tumors (p=0.04) and triple negative tumors (p= 0.03). Breast cancer in women ≤25 years is uncommon. An adequate medical education of young women and physicians is necessary.
C1 [Ben Abdelkrim, Soumaya] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Fathallah, Khadija] Farhat Hached University Hospital, Department of GynecologySousse, Tunisia.
[Rouatbi, Rim] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Ayachi, Malak] Cancer RegistrySousse, Tunisia.
[Hmissa, Sihem] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Mokni, Moncef] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
RP Ben Abdelkrim, S (reprint author), Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
EM benabdelkrims@voila.fr
CR Missaoui N, Jaidene L, Ben Abdelkrim S, Ben Abdelkader A, Beizig N, Ben Yaacoub L, Yaacoubi MT, Hmissa S, 2011, Breast cancer in Tunisia: clinical and pathological findings. Asian Pac J Cancer Prev 12(1):169–172
Missaoui N, Landolsi H, Jaidaine L, Ben Abdelkader A, Yaacoubi MT,Hmissa S, 2012, Breast cancer in central Tunisia: an earlier age at diagnosis and incidence increase over a 15-year period. Breast J 18(3):289–291
Narod SA, 2012, Breast cancer in young women. Nat Rev Clin Oncol 9:460–470
Kothari AS, Beechey-Newman N, D’Arrigo C, Hanby AM, Ryder K, Hamed H, Fentiman IS, 2002, Breast carcinoma in women age 25 years or less. Cancer 94(3):606–614
Khanfir A, Frikha M, Kallel F, Meziou M, Trabelsi K, Boudawara T, Mnif J, Daoud J, 2006, Breast cancer in young women in the south of Tunisia. Cancer Radiother 10(8):565–571
Dimitrakakis C, Tsigginou A, Zagouri F, Marinopoulos S, Sergentanis TN, Keramopoulos A, Liakou P, Zografos GC, Papadimitriou CA, Dimopoulos MA, Antsaklis A, 2013, Breast cancer in women aged 25 years and younger. Obstet Gynecol 121(6):1235–1240
Paillocher N, Lacourtoisie SA, Fondrinier E, Catala L, Morand C, Boursier J, Guerin O, Descamps P, 2006, Infiltrating breast cancer in women younger than 25 years: 13 cases. PresseMed 35(11 Pt 1): 1618–1624
Yao S, Xu B, Ma F, Liao Y, Fan Y, 2009, Breast cancer in women younger than 25: clinicopathological features and prognostic factors. Ann Oncol 20(2):387–389
Alipour S, Omranipour R, Jahanzad I, Bagheri K, 2013, Very young breast cancer in a referral center in Tehran, Iran; review of 55 cases aged 25 or less throughout 33 years. Asian Pac J Cancer Prev 14(11):6529–6532
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, eds,, 2012, WHO classification of tumours of the breast, fourth edition. IARC Press, Lyon
Elston CW, Ellis IO, 1991, Pathological prognostic factors in breast cancer.I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410
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Lin CH, Liau JY, Lu YS, Huang CS, Lee WC, Kuo KT, Shen YC, Kuo SH, Lan C, Liu JM, Kuo WH, Chang KJ, Cheng AL, 2009, Molecular subtypes of breast cancer emerging in young women in Taiwan: evidence for more than just westernization as a reason for the disease in Asia. Cancer Epidemiol Biomarkers Prev 18(6): 1807–1814
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Khurshid A, Faridi N, Arif AM, Naqvi H, Tahir M, 2013, Breast lesions in adolescents and young women in Pakistan: a 5 year study of significance of early recognition. Asian Pac J Cancer Prev 14(6): 3465–3467
Ntekim A, Nufu FT, Campbell OB, 2009, Breast cancer in young women in Ibadan, Nigeria. Afr Health Sci 9(4):242–246
Keegan TH, DeRouen MC, Press DJ, Kurian AW, Clarke CA, 2012, Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res 14(2):R55
Gabriel CA, Domchek SM, 2010, Breast cancer in young women. Breast Cancer Res 12(5):212
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ColleoniM, Rotmensz N, Robertson C, Orlando L, Viale G, Renne G, Luini A, Veronesi P, Intra M, Orecchia R, Catalano G, Galimberti V, Nole F, Martinelli G, Goldhirsch A, 2002, Very young women, <35 years, with operable breast cancer: features of disease at presentation. Ann Oncol 13(2):273–279
Tichy JR, Lim E, Anders CK, 2013, Breast cancer in adolescents and young adults: a review with a focus on biology. J Natl Compr Canc Netw 11(9):1060–1069
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Andre F, Domont J, Delaloge S, 2007, What can breast cancer molecular sub-classification add to conventional diagnostic tools? Ann Oncol 18(Suppl 9):ix33–6
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D, 2000, Molecular portraits of human breast tumours. Nature 17;406(6797):747–752
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D, 2003, Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100(14):8418–8423
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Keegan TH, Press DJ, Tao L, Derouen MC, Kurian AW, Clarke CA, Gomez SL, 2013, Impact of breast cancer subtypes on threeyear survival among adolescent and young adult women. Breast Cancer Res 15(5):R95
Ben Abdelkrim S, Trabelsi A, Missaoui N, Beizig N, Bdioui A, Anjorin A, Jomaa W, Mokni M, 2010, Distribution of molecular breast cancer subtypes among Tunisianwomen and correlation with histopathological parameters: a study of 194 patients. Pathol Res Pract 206(11):772–775
Madaras L, Szasz MA, Baranyak Z, Tokes AM, Szittya L, Lotz G, Szekely B, Szentmartoni G, Dank M, Baranyai Z, Kulka J, 2012, Morphological and immunophenotypical heterogeneity in breast cancers of young and elderly women. Magy Onkol 56(2):75–78
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 553
EP 561
DI 10.1007/s12253-015-9944-5
PG 9
ER
PT J
AU Zhou, X
Zheng, R
Zhang, H
He, T
AF Zhou, Xiaodong
Zheng, Ruiguo
Zhang, Huifang
He, Tianlin
TI Pathway Crosstalk Analysis of Microarray Gene Expression Profile in Human Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma; Pathway crosstalk; Protein-protein interaction network
ID Human hepatocellular carcinoma; Pathway crosstalk; Protein-protein interaction network
AB Liver cancer is the third most common cause of cancer death in the world. Hepatocellular carcinoma (HCC) is the main pathological types in liver cancer, which amounts to 70–85 % of primary liver cancer in the world and 90 % in China. The aim of this study was to establish a PPI network and a pathway crosstalk network to isolate important dysfunctional pathways which play an important role in the pathogenesis of HCC. System biology approach was used in this research. A PPI network was firstly built and then a dysfunctional crosstalk network of HCC related pathways was constructed. Several important significant dysfunctional crosstalk pathways were identified. Basal transcription factors (hsa03022), Glycerophospholipid metabolism (hsa00564) and Metabolism of xenobiotics by cytochrome P450 (hsa00980) were significantly interact with Pathway in cancer (hsa05200). Besides, pathway Axon guidance (hsa04360) was also dysfunctional crosstalk with Pathway in cancer (hsa05200). The crosstalks among these pathways reveal some evidence that the pathways closely cooperated and play important tasks in HCC progression. Besides, the pathway hsa04360 dysfunctional crosstalk with the hsa05200 indicates there would be a same mechanism for HCC invasion and migration.
C1 [Zhou, Xiaodong] PLA 535 Hospital, Department of General Surgery, 418008 Huaihua, China.
[Zheng, Ruiguo] PLA 535 Hospital, Department of General Surgery, 418008 Huaihua, China.
[Zhang, Huifang] PLA 535 Hospital, Department of Emergency, 418008 Huaihua, China.
[He, Tianlin] Changhai Hospital, Department of General Surgery, No.168 Changhai Road, Yangpu District, 200433 Shanghai, China.
RP He, T (reprint author), Changhai Hospital, Department of General Surgery, 200433 Shanghai, China.
EM Skyrainhe@163.com
CR Parkin DM, Bray F, Ferlay J, Pisani P, 2001, Estimating the world cancer burden: globocan 2000. Int J Cancer 94(2):153–156
Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP, 2006, The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45(4): 529–538
Tang Z-Y, Ye S-L, Liu Y-K, Qin L-X, Sun H-C, Ye Q-H, Wang L, Zhou J, Qiu S-J, Li Y, 2004, A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130(4):187–196
Berger JC, Vander Griend D, Stadler WM, Rinker-Schaeffer C, 2004, Metastasis suppressor genes: signal transduction, cross-talk and the potential for modulating the behavior of metastatic cells. Anti-Cancer Drugs 15(6):559–568
Berasain C, Ujue Latasa M, Urtasun R, Goni S, Elizalde M, Garcia- Irigoyen O, Azcona M, Prieto J, AvilaMA, 2011, Epidermal growth factor receptor, EGFR, crosstalks in liver cancer. Cancer 3(2):2444– 2461
Dai R, Chen R, Li H, 2009, Cross-talk between PI3K/Akt andMEK/ ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells. Int J Oncol 34(6):1749–1757
Berasain C, Castillo J, Prieto J, Avila MA, 2007, New molecular targets for hepatocellular carcinoma: the ErbB1 signaling system. Liver Int 27(2):174–185
Chen L, Wang R-S, Zhang X-S, 2009, Biomolecular networks: methods and applications in systems biology, vol 10. Wiley
Zhao X-M, Wang R-S, Chen L, Aihara K, 2008, Uncovering signal transduction networks from high-throughput data by integer linear programming. Nucleic Acids Res 36(9):e48–e48
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 563
EP 569
DI 10.1007/s12253-014-9855-x
PG 7
ER
PT J
AU Jederan,
Lovey, J
Szentirmai, Z
Hitre, E
Lerant, G
Horvath, K
Godeny, M
AF Jederan, Eva
Lovey, Jozsef
Szentirmai, Zoltan
Hitre, Erika
Lerant, Gergely
Horvath, Katalin
Godeny, Maria
TI The Role of MRI in the Assessment of the Local Status of Anal Carcinomas and in Their Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MRI; Anal cancer; Staging of anal cancer; Chemoradiation therapy
ID MRI; Anal cancer; Staging of anal cancer; Chemoradiation therapy
AB This study aims to define the role of Magnetic Resonance (MR) examinations in the assessment and therapy of anal cancer (AC), and to present the main features of the MR examinations and the typical tumor spread pattern. The MR examinations of 67 anal cancer patients with histologically confirmed planocellular cancer were analyzed retrospectively. The tumor size and the signal intensity, the nodal status were examined before and after the treatment, and in recidive tumors (N=13). At the time of the diagnosis the primary tumor was in early stage (Tis, T1, T2) in 71.5%of the cases, and it was localized in 97 %. In 97.4 % of the cases the tumor had relatively increased signal intensities compared to the adjacent muscles. Patients received chemo-radiotherapy (CRT). After CRT in 26 out of 39 patients (66.7%) the size of the tumor decreased (in 75 %), and the signal intensity decreased on the T2 weighted (T2w) images. In the residual tumor cases (19/39) verified 6 patients out of 19 had further decrease in size, and signal intensity a year after the end of the therapy. The MR examination plays a key role in the therapy of AC, by assessing the precise local status, the possible recidive tumors, and monitoring the therapy.
C1 [Jederan, Eva] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Lovey, Jozsef] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Szentirmai, Zoltan] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Hitre, Erika] National Institute of Oncology, Department of Chemotherapy and ClinicopharmacologyBudapest, Hungary.
[Lerant, Gergely] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Horvath, Katalin] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Godeny, Maria] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
RP Jederan, (reprint author), National Institute of Oncology, Center of Radiology, Budapest, Hungary.
EM jederan@t-online.hu;jederan@oncol.hu
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 571
EP 579
DI 10.1007/s12253-014-9857-8
PG 9
ER
PT J
AU Wu, H
Gu, Yh
Wei, L
Guo, Tk
Zhao, Y
Su, G
Li, J
Xie, Xd
AF Wu, Hua
Gu, Yuan-hui
Wei, Li
Guo, Tian-kang
Zhao, Yong
Su, Gang
Li, Jiong
Xie, Xiao-dong
TI Association of Romo1 Gene Genetic Polymorphisms with Risk of Gastric Cancer in Northwestern Chinese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Romo1 gene; Single nucleotide polymorphisms; DHPLC
ID Gastric cancer; Romo1 gene; Single nucleotide polymorphisms; DHPLC
AB Increased expression of reactive oxygen species modulator 1 protein-triggered reactive oxygen species production was reported in the mitochondria of various cancer cell lines. To date there is no report on association between Romo1 gene polymorphisms and gastric cancer risk. To investigate the relationship between Romo1 gene polymorphisms and GC risk, we conducted a case-control study in a population from northwest China (358 GC patients and 412 healthy controls). The genotypes of two SNPs were determined with PCR– denaturing high-performance liquid chromatography and direct DNA sequencing. We found that the genotype and allele distributions of two polymorphisms were significantly different in GC patients compared with controls, When the wild type of two loci were served as the reference group, respectively, significantly increased risk for gastric cancer were associated with rs6060566 TC genotype (Adjusted OR= 1.525, 95 % CI =1.126–2.138), rs6060567 GC genotype (Adjusted OR=1.641, 95 % CI =1.238–2.291) and CC genotype (Adjusted OR=1.594, 95%CI =1.102–2.973). This effect was more pronounced in patients with smoking, alcohol consumption, H.pylori infection,and male patients subgroups. Haplotypes analysis of two genetic variants showed that the most common haplotype TG displayed the strongest evidence of association with GC (corrected P=9.30×10−5), and was associated with protection against GC (OR=0.584). Whereas the CC haplotypes had significant correlation with GC risk (OR=1.732). These findings suggested genetic polymorphisms of Romo1 gene were associated with significant risk of GC in Northwestern Chinese population, which is strengthened by alcohol use, smoking, H.pylori infection or male patients.
C1 [Wu, Hua] Lanzhou University, School of Basic Medical Science, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 730000 Lanzhou, Gansu Province, China.
[Gu, Yuan-hui] People’s Hospital of Gansu Province, Surgical Department, 730000 Lanzhou, Gansu Province, China.
[Wei, Li] People’s Hospital of Gansu Province, Surgical Department, 730000 Lanzhou, Gansu Province, China.
[Guo, Tian-kang] People’s Hospital of Gansu Province, Surgical Department, 730000 Lanzhou, Gansu Province, China.
[Zhao, Yong] General Hospital of Lanzhou Military Region, 730050 Lanzhou, Gansu Province, China.
[Su, Gang] Lanzhou University, School of Basic Medical Science, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 730000 Lanzhou, Gansu Province, China.
[Li, Jiong] Lanzhou University, School of Basic Medical Science, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 730000 Lanzhou, Gansu Province, China.
[Xie, Xiao-dong] Lanzhou University, School of Basic Medical Science, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 730000 Lanzhou, Gansu Province, China.
RP Xie, Xd (reprint author), Lanzhou University, School of Basic Medical Science, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 730000 Lanzhou, China.
EM xdxie@lzu.edu.cn;xdxiegenetics@outlook.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 581
EP 587
DI 10.1007/s12253-014-9858-7
PG 7
ER
PT J
AU Baric, M
Kulic, A
Sirotkovic-Skerlev, M
Dedic Plavetic, N
Vidovic, M
Horvatic-Herceg, G
Vrbanec, D
AF Baric, Marina
Kulic, Ana
Sirotkovic-Skerlev, Maja
Dedic Plavetic, Natalija
Vidovic, Marina
Horvatic-Herceg, Gordana
Vrbanec, Damir
TI Circulating Her-2/Neu Extracellular Domain in Breast Cancer Patients-Correlation with Prognosis and Clinicopathological Parameters Including Steroid Receptor, Her-2/Neu Receptor Coexpression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER-2/neu ECD; Breast cancer; Prognosis; Steroid receptor/HER-2/neu receptor coexpression
ID HER-2/neu ECD; Breast cancer; Prognosis; Steroid receptor/HER-2/neu receptor coexpression
AB HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. The aim of this study was to analyze the relationship between HER-2/neu extracellular domain in the serum and the prognosis in breast cancer patients. We also correlated HER-2/neu ECD with various clinicopathological factors including steroid receptor, HER-2/neu receptor coexpression. The serum from seventy nine patients with invasive breast cancer and twenty individuals without malignancy was analyzed using the enzymelinked immune adsorbent assay method. The cut-off value was estimated by the ROC curve analysis (15.86 μg/L). HER-2/neu ECD values in the serum of patients with breast cancer were significantly higher than in control subjects. Circulating HER-2/neu ECD was significantly associated with the histological grade of tumors and the status of axillary lymph nodes. Negative correlation was observed between HER-2/neu ECD in the serumand estrogen receptor positivity. When we analyzed HER-2/neu ECD in relation with coexpression of steroid receptor and HER-2/neu receptor in tissue, statistically higher values were found in the subgroup of patients with steroid receptor negative, HER-2/neu negative tumors than in the other subgroups. HER-2/neu ECD was not an independent factor in the univariate and multivariate analysis. However, elevated HER-2/neu ECD levels were found in patients with breast cancer possessing more aggressive phenotype.
C1 [Baric, Marina] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Kulic, Ana] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical OncologyZagreb, Croatia.
[Sirotkovic-Skerlev, Maja] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical OncologyZagreb, Croatia.
[Dedic Plavetic, Natalija] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Vidovic, Marina] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
[Horvatic-Herceg, Gordana] University Hospital Center Zagreb, Clinical Department of Nuclear Medicine and Radiation ProtectionZagreb, Croatia.
[Vrbanec, Damir] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, Kispaticeva 12, 10 000 Zagreb, Croatia.
RP Baric, M (reprint author), University Hospital Center Zagreb and Zagreb Medical School, Department of Medical Oncology, 10 000 Zagreb, Croatia.
EM marina.baric11@gmail.com
CR Slamon DJ, ClarkGM,Wong SG, LevinWJ, Ullrich A,McguireWL, 1987, Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 589
EP 595
DI 10.1007/s12253-014-9859-6
PG 7
ER
PT J
AU Nemes, K
Csoka, M
Nagy, N
Mark,
Varadi, Zs
Danko, T
Kovacs, G
Kopper, L
Sebestyen, A
AF Nemes, Karolina
Csoka, Monika
Nagy, Noemi
Mark, Agnes
Varadi, Zsofia
Danko, Titanilla
Kovacs, Gabor
Kopper, Laszlo
Sebestyen, Anna
TI Expression of Certain Leukemia/Lymphoma Related microRNAs and its Correlation with Prognosis in Childhood Acute Lymphoblastic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miRNA-128b miRNA-223; Childhood ALL; Prognosis; Relapse
ID miRNA-128b miRNA-223; Childhood ALL; Prognosis; Relapse
AB In spite of the improved efficacy of therapy, it still fails in 15–20 % of childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered expression of certain miRNAs (miRs) have been described in ALL with potential effect on prognosis. Presence of certain miRs (miRNA-16, −21, −24, −29b, −128b, −142-3p, −155, −223) was characterized in human lymphoma and leukemia cells by real-time PCR. Expression of miRs in pediatric ALL patients (n=24) was measured before chemotherapy, at conventional response checkpoints and at relapse. Correlation between altered miR expression and response to prednisolone at day 8 of therapy and long term prognosis was statistically analysed. Overexpression of "oncomiR/inflammamiR"-21 – which is characteristic in different tumors—was missing in human ALL cells. However, higher expression of miR-128b and lower expression of miR-223 is generally characteristic for human ALL cell lines and ALL cells isolated from pediatric patients. Correlation was shown between miR-128b expression and prognosis, prednisolone response and survival data in childhood ALL. Expression of miR-128b and miR-223—both are leukemia specific—changed in parallel with percentage of bone marrow blasts in remission and during relapse. Therefore, we suggest that overexpression of miR-128b and downregulation of miR-223 shows a significant correlation with treatment response and prognosis in childhood ALL.
C1 [Nemes, Karolina] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9., 1094 Budapest, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9., 1094 Budapest, Hungary.
[Nagy, Noemi] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
[Mark, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
[Varadi, Zsofia] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9., 1094 Budapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9., 1094 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26., 1085 Budapest, Hungary.
RP Csoka, M (reprint author), Semmelweis University, 2nd Department of Pediatrics, 1094 Budapest, Hungary.
EM dr.csoka.monika@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 597
EP 604
DI 10.1007/s12253-014-9861-z
PG 8
ER
PT J
AU Damjanovic, A
Matic, ZI
Ðordic, M
Ðurovic, NM
Nikolic, S
Roki, K
Milovanovic, Z
Antic-Stankovic, J
Dzodic, R
Damjanovic, S
Kanjer, K
Abu Rabi, Z
Juranic, Z
AF Damjanovic, Ana
Matic, Z Ivana
Ðordic, Marija
Ðurovic, Nikolic Marina
Nikolic, Srdan
Roki, Ksenija
Milovanovic, Zorka
Antic-Stankovic, Jelena
Dzodic, Radan
Damjanovic, Svetozar
Kanjer, Ksenija
Abu Rabi, Zaki
Juranic, Zorica
TI Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; Herceptin; Metformin; PBMC
ID Cancer; Herceptin; Metformin; PBMC
AB The aim of research was to determine the effects of maximally therapeutically achievable concentrations of metformin on malignant cells and healthy peripheral blood mononuclear cells (PBMC). Eight patients with T2D or hyperglycemia and nine healthy volunteers were included in the study. For determination of the influence of metformin on the phenotype of breast carcinoma, 1,410 patients with surgically removed tumors were included. From this group 37 breast cancer patients had DM type 2 or hyperglycemia and were pretreated with metformin alone or sometimes in combination with other antidiabetic drugs. Our results proved that metformin at low concentrations inducedmild decrease in survival of malignant cells and PBMC stimulated for proliferation, but it didn’t affect survival of resting PBMC. The effects of plasma of hyperglycemic patients who were under metformin therapy on autologous PBMC-induced decrease in survival of MDAMB- 361 cells, was noticeable in some patients. Metformin pretreatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival. The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p<0.013), while the number of patientswith ER+PR+ tumors was not significantly changed (p<0.832). In conclusion, therapeutically used concentrations of metformin exhibit mild cytotoxic action on malignant and dividing normal cells pointing to its preferred role in malignant and autoimmune diseases. The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors.
C1 [Damjanovic, Ana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Matic, Z Ivana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Ðordic, Marija] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Ðurovic, Nikolic Marina] Clinical Center of Serbia, Clinic of Endocrinology, Diabetes and Metabolic Diseases, dr Subotica 13, 11000 Belgrade, Serbia.
[Nikolic, Srdan] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Roki, Ksenija] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Milovanovic, Zorka] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Antic-Stankovic, Jelena] University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
[Dzodic, Radan] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Damjanovic, Svetozar] Clinical Center of Serbia, Clinic of Endocrinology, Diabetes and Metabolic Diseases, dr Subotica 13, 11000 Belgrade, Serbia.
[Kanjer, Ksenija] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Abu Rabi, Zaki] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Juranic, Zorica] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
RP Juranic, Z (reprint author), Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
EM juranicz@ncrc.ac.rs
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 605
EP 612
DI 10.1007/s12253-014-9864-9
PG 8
ER
PT J
AU Banovic, M
Mahovlic, V
Salopek, MK
Banovic, V
Babic, I
Oreskovic, S
Babic, D
AF Banovic, Maja
Mahovlic, Vesna
Salopek, Meljanac Kristina
Banovic, Vladimir
Babic, Ivan
Oreskovic, Slavko
Babic, Damir
TI The Value of HPV-HR DNA Testing During the Follow-Up After Treatment of CIN3/AIS
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; Preinvasive cervical disease; Postconisation; HPV-HR DNA test; Follow-up
ID Human papillomavirus; Preinvasive cervical disease; Postconisation; HPV-HR DNA test; Follow-up
C1 [Banovic, Maja] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, Petrova 13, 10000 Zagreb, Croatia.
[Mahovlic, Vesna] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Pathology and CytologyZagreb, Croatia.
[Salopek, Meljanac Kristina] University of Zagreb, School of Medicine, Department of PathologyZagreb, Croatia.
[Banovic, Vladimir] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, Petrova 13, 10000 Zagreb, Croatia.
[Babic, Ivan] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, Petrova 13, 10000 Zagreb, Croatia.
[Oreskovic, Slavko] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, Petrova 13, 10000 Zagreb, Croatia.
[Babic, Damir] University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Pathology and CytologyZagreb, Croatia.
RP Banovic, M (reprint author), University of Zagreb, School of Medicine, Clinical Hospital Center Zagreb, Department of Obstetrics and Gynecology, 10000 Zagreb, Croatia.
EM mzanko03@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 613
EP 617
DI 10.1007/s12253-014-9865-8
PG 5
ER
PT J
AU Hever, VN
Pentek, M
Ballo, A
Gulacsi, L
Baji, P
Brodszky, V
Damasdi, M
Bognar, Z
Toth, Gy
Buzogany, I
Szanto,
AF Hever, V Noemi
Pentek, Marta
Ballo, Andras
Gulacsi, Laszlo
Baji, Petra
Brodszky, Valentin
Damasdi, Miklos
Bognar, Zita
Toth, Gyorgy
Buzogany, Istvan
Szanto, Arpad
TI Health Related Quality of Life in Patients with Bladder Cancer: A Cross-Sectional Survey and Validation Study of the Hungarian Version of the Bladder Cancer Index
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Quality of life; EQ-5D; FACT-Bl; Bladder Cancer Index; Validation
ID Bladder cancer; Quality of life; EQ-5D; FACT-Bl; Bladder Cancer Index; Validation
AB Health-related quality of life (HRQoL) is an important outcome in oncology care although an underexplored area in bladder cancer (BC). Our aims were to assess HRQoL of patients with BC, analyse relationships between diverse HRQoL measures and validate the Hungarian version of the Bladder Cancer Index (BCI) questionnaire. A cross-sectional survey was performed among patients with BC (N=151). Validated Hungarian versions of the FACT-Bl, SF-36 and EQ-5D were applied and SF-6D was derived. Psychometric analysis of the Hungarian BCI was performed. Pearson correlations between the five measures were analysed. Deterioration in SF-36 Physical Functioning was detected among patients aged 45–64 years. The EQ-5D score did not differ significantly from the age-matched population norm. Correlations between the FACT-Bl, EQ-5D and SF-6D utility measures were strong (r>0.6). Cronbach alpha coefficients of the Hungarian BCI ranged from 0.75 to 0.97 and factor analysis confirmed that data fit to the six predefined subdomains. Test-retest correlations (reliability, N=50) ranged from 0.67 to 0.87 and interscale correlations between urinary, bowel and sexual BCI domains were weak or moderate (r=0.29 to 0.49). Convergent validity revealed a stronger correlation with FACT-Bl (r=0.126 to 0.719) than with generic health state scores (r=0.096 to 0.584). Results of divergent validity of the Hungarian BCI by treatment groups by Kruskal Wallis test were promising although limited by low sample sizes in cystectomy subgroups. Generic health state measures have limited capacity to capture HRQoL impact of BC. Validity tests yielded favourable results for the Hungarian BCI. Mapping studies to estimate utility scores from FACT-Bl are encouraged but less recommendable with the BCI.
C1 [Hever, V Noemi] Corvinus University of Budapest, Department of Health Economics, Fovam ter 8., 1093 Budapest, Hungary.
[Pentek, Marta] Corvinus University of Budapest, Department of Health Economics, Fovam ter 8., 1093 Budapest, Hungary.
[Ballo, Andras] University of Pecs, Department of Urology, Munkacsy Mihaly utca 2, 7621 Pecs, Hungary.
[Gulacsi, Laszlo] Corvinus University of Budapest, Department of Health Economics, Fovam ter 8., 1093 Budapest, Hungary.
[Baji, Petra] Corvinus University of Budapest, Department of Health Economics, Fovam ter 8., 1093 Budapest, Hungary.
[Brodszky, Valentin] Corvinus University of Budapest, Department of Health Economics, Fovam ter 8., 1093 Budapest, Hungary.
[Damasdi, Miklos] University of Pecs, Department of Urology, Munkacsy Mihaly utca 2, 7621 Pecs, Hungary.
[Bognar, Zita] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti ut 12, 7624 Pecs, Hungary.
[Toth, Gyorgy] Josa Andras Hospital, Department of Urology, Szent Istvan ut 68, 4400 Nyiregyhaza, Hungary.
[Buzogany, Istvan] Peterfy Hospital, Department of Urology, Peterfy S u. 8-20, 1076 Budapest, Hungary.
[Szanto, Arpad] University of Pecs, Department of Urology, Munkacsy Mihaly utca 2, 7621 Pecs, Hungary.
RP Pentek, M (reprint author), Corvinus University of Budapest, Department of Health Economics, 1093 Budapest, Hungary.
EM marta.pentek@uni-corvinus.hu
CR Ploeg M, Aben KK, Kiemeney LA, 2009, The present and future burden of urinary bladder cancer in the world. World J Urol 27(3): 289–293., DOI 10.1007/s00345-009-0383-3
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Aboumohamed AA, Raza SJ, Al-Daghmin A, Tallman C, Creighton T, Crossley H, Dailey S, Khan A, Din R,MehedintD,Wang K, ShiY, Sharif M, Wilding G, Weizer A, Guru KA, 2014, Health-related quality of life outcomes after robot-assisted and open radical cystectomy using a validated bladder-specific instrument: a multiinstitutional study. Urology., DOI 10.1016/j.urology.2014.02.024
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 619
EP 627
DI 10.1007/s12253-014-9866-7
PG 9
ER
PT J
AU Abderrahmane, R
Louhibi, L
Moghtit, ZF
Boubekeur, A
Benseddik, K
Boudjema, A
Benrrahal, F
Aberkane, M
Fodil, M
Saidi-Mehtar, N
AF Abderrahmane, Rym
Louhibi, Lotfi
Moghtit, Zohra Fatima
Boubekeur, Amina
Benseddik, Khedidja
Boudjema, Abdellah
Benrrahal, Fouzia
Aberkane, Meriem
Fodil, Mostefa
Saidi-Mehtar, Nadhira
TI TP53 Arg 72Pro and MDM2 SNP309 Polymorphisms and Colorectal Cancer Risk: A West Algerian Population Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Polymorphism; TP53 Arg72Pro; MDM2 SNP309; CRC; Algerian population; Case/Control study
ID Polymorphism; TP53 Arg72Pro; MDM2 SNP309; CRC; Algerian population; Case/Control study
AB The tumor suppressor gene TP53 and its regulator MDM2 are both key players involved in multiple pathways including apoptosis, cellular transcriptional control and cell cycle regulation. Common germline polymorphisms in these genes may affect colorectal cancer (CRC) susceptibility. An arginine-to-proline substitution at codon 72 in the TP53 gene is reported to decrease apoptotic potential, while a thymine-toguanine polymorphism at nucleotide 309 (named SNP309) of murine double minute 2 MDM2 gene increases its transcription. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer in the Algerian population was addressed in this study. DNA samples from 121 controls and 116 cases were genotyped for these two polymorphisms by PCR/RFLP then confirmed by sequencing. Unexpectedly no significant association was found between this potential marker TP53 Arg72Pro and CRC (p>0.05). However, our findings reveal that individuals with the MDM2 SNP309 GG genotype have a low risk of CRC as compared to the TT genotype (OR=0.49; 95%CI: 0.24–0.98, p=0.04),withmore significance for females (OR=0.16; 95 % CI: 0.06–0.41, p<0.05). Moreover, no significant association was observed between the combined TP53 and MDM2 genotypes and CRC. Contrary to initial expectations that the GG genotype with high MDM2 levels would increase cancer risk, our results demonstrate that the MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer. This is suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.
C1 [Abderrahmane, Rym] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Louhibi, Lotfi] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Moghtit, Zohra Fatima] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Boubekeur, Amina] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Benseddik, Khedidja] Centre de Recherche en Cancerologie de MarseilleMarseille, France.
[Boudjema, Abdellah] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Benrrahal, Fouzia] Centre Hospitalier d’Oran, 76, Bd Dr Benzerdjeb - PlateauOran, Algeria.
[Aberkane, Meriem] Universite d’Oran, Faculte de Medecine, Departement de Pharmacie, BP 1524 El M’naouer, 31000 Oran, Algeria.
[Fodil, Mostefa] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
[Saidi-Mehtar, Nadhira] Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, BP 1505 El M’naouer, 31000 Oran, Algeria.
RP Abderrahmane, R (reprint author), Universite des Sciences et de la Technologie d’Oran- Mohamed BOUDIAF-USTOMB, Faculte des sciences de la nature et de la vie, Departement de Genetique Moleculaire Appliquee, Laboratoire de Genetique Moleculaire et Cellulaire, 31000 Oran, Algeria.
EM abderrahmane_rym@yahoo.fr
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Qin X, Peng Q, TangW, Lao X, Chen Z, Lai H, Deng Y, Mo C, Sui J, Wu J, Zhai L, Yang S, Li S, Zhao J, 2013, An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk. PLoS ONE 8(9):0076031
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 629
EP 635
DI 10.1007/s12253-014-9867-6
PG 7
ER
PT J
AU Wu, J
Chen, P
Xie, Yg
Gong, Nm
Sun, Ll
Sun, Chf
AF Wu, Jing
Chen, Ping
Xie, Yang-gui
Gong, Nian-mei
Sun, Lin-lin
Sun, Chun-feng
TI Comparison of the Effectiveness and Safety of Ultrasoundand CT-Guided Percutaneous Radiofrequency Ablation of Non-Operation Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE US guidance; CT guidance; Radiofrequency ablation; Hepatocellular carcinoma
ID US guidance; CT guidance; Radiofrequency ablation; Hepatocellular carcinoma
AB To retrospectively compare the effectiveness and safety of ultrasound (US)- and computer tomography (CT)- guided percutaneous radiofrequency ablation (PRFA) in treating patients with non-operation hepatocellular carcinoma (HCC). Forty patients with non-operation HCC who were treated with US-guided PRFA (20 patients with 24 HCC lesions) or CT-guided PRFA (20 patients with 27 HCC lesions) were enrolled in this study. Follow-up was performed with US and CT/MRI. Complete ablation rate, local recurrence rate, and overall survival rate were used to evaluate the efficacy of the two therapeutic choices. The PRFA-related complications including hilar bile duct injury, sepsis, liver failure, renal dysfunction, peritoneal hemorrhage, and skin burn were assessed. The operation time of CT-guided group was significantly longer than that of the US-guided group (P<0.05). The single ablation times for tumors with similar size showed no significant difference between the two groups (P>0.05). The differences in complete ablation rate (79.2 vs. 88.9 %, P>0.05) and local recurrence rate (16.7 vs. 14.8 %, P>0.05) between US- and CT-guided groups were not statistically significant. In the US-guided group, the 1-, 2-, and 3- year overall survival rates were 85, 74, and 68%, respectively, while they were 84, 72, and 58%in the CT-guided group. The differences were not statistically significant (P>0.05). No severe complications were found in the two groups. Both US- and CT-guided PRFA are safe and effective therapies for patients with HCC when surgical options are precluded.
C1 [Wu, Jing] The Third Hospital Affiliated to Nantong University, Department of Ultrasound, 226006 Nantong, China.
[Chen, Ping] The Third Hospital Affiliated to Nantong University, Department of Oncology, 226006 Nantong, China.
[Xie, Yang-gui] The Hospital Affiliated to Nantong University, Department of Ultrasound, Xisi Road No. 20, 226006 Nantong, China.
[Gong, Nian-mei] The Third Hospital Affiliated to Nantong University, Department of Ultrasound, 226006 Nantong, China.
[Sun, Lin-lin] The Third Hospital Affiliated to Nantong University, Department of Ultrasound, 226006 Nantong, China.
[Sun, Chun-feng] The Third Hospital Affiliated to Nantong University, Department of Medical Imaging, 226006 Nantong, China.
RP Xie, Yg (reprint author), The Hospital Affiliated to Nantong University, Department of Ultrasound, 226006 Nantong, China.
EM xieyanggui34@hotmail.com
CR Llovet JM, Burroughs A, Bruix J, 2003, Hepatocellular carcinoma. Lancet 362(9399):1907–1917., DOI 10.1016/S0140-6736(03)14964-1
Shiina S, 2009, Image-guided percutaneous ablation therapies for hepatocellular carcinoma. J Gastroenterol 44(Suppl 19):122–131., DOI 10.1007/s00535-008-2263-9
Lencioni R, Crocetti L, 2013, Image-guided ablation for hepatocellular carcinoma. Recent Results Cancer Res Fortschr Der Krebsforschung Progres Dans Les Rech Sur Le Cancer 190:181– 194., DOI 10.1007/978-3-642-16037-0_12
Kim PN, Choi D, Rhim H, Rha SE, Hong HP, Lee J, Choi JI, Kim JW, Seo JW, Lee EJ, Lim HK, 2012, Planning ultrasound for percutaneous radiofrequency ablation to treat small, 0.05).
C1 [Mate, Miklos] Saint Emerich Hospital Budapest, Surgical DepartmentBudapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
RP Mate, M (reprint author), Saint Emerich Hospital Budapest, Surgical Department, Budapest, Hungary.
EM miklos.mate@gmail.com
CR Croft J, Parry E, Jenkins GJ, Doak SH, Baxter JN, Griffiths AP, Brownn TH, Parry JM, 2002, Analysis of the premalignant stages of Barrett’s oesophagus through to adenocarcinoma by comparative genomic hybridization. Eur Gastroenterol Hepatology 14:1179–1186
Souza RF,Morales CP, Spechler SJ, 2001, A conceptual approach to understanding the molecular mechanism of cancer development in Barrett’s esophagus, Review, alimentary pharmacology. Therapy 15: 1087–1100
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Geddert H, Zeriouh M, Wolter M, Heise JW, Gabbert HE, Sarbia M, 2002, Gene amplification and proteins overexpression of c-erb-b2 in Barrett’s carcinoma and its precursor laesions A. J Clin Pathol 117: 558–566
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Ramel S, 2002, Barrett’s Esophagus: model of neoplastic progression. World J Surg, 73):1697–1703
Schneider PM, Stoeltzing O, Roth JA, Hoelscher AH, Wegerer S, Mizumoto S et al, 2000, p53 mutational status improves estimation fo prognosis in patients with curatively rsected adenocarcinoma in Barrett’s esophagus. Clin Cancer Res 6:3153–3158
Neuhaus H, Terheggen G, Rutz EM, Vieth M, Schumacher B, 2012, Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett’s esophagus. Endocopy 44:1105–1113
Seery JP, 2002, Stem cells of the oesophageal epithelium. J Cell Sci 115:1783–1789
Sarosi G, Brown G, Jaiswal K, Feagins LA, Lee E, Crook TW, Souza RF, Zou YS, Shay JW, Spechler SJ, 2008, Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus. Dis Esophagus 21:43–50
Arul GS, Moorghen M, Myerscough N, Alderson DA, Spicer RD, Corfield AP, 2000)Mucin gene expression in Barrett’s esophagus: an in situ hybridization and immunohistochemical study. Gut 47:753– 761
Burjonrappa SC, Reddimasu S, Nawaz Z, Gao X, Sharma P, Loggie B, 2007, Mucin expression profile in Barrett’s, dysplasia, adenocarcinoma sequence int he esophagus. Indian J Cancer Year 44(1):1–5
Rahn JJ, Shen Q, Mah BK, Hugh JC, 2004, MUC1 initiates a calcium signal after ligation by intercellular adhesion molecule-1. J Biol Chem 279:29386–29390
Sharma P, Sidorenko EI, 2005, Are screening and surveillance for Barrett’s esophagus really worthhile ? Gut, 54):27–32
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Galipeau PC, Li X, Blount PL, Maley CC, Sanchez CA, Odze RD, Ayub K, Rabinovitch PS, Vaughan TL, Reid BJ, 2007, NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med 4:e67
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 669
EP 673
DI 10.1007/s12253-014-9873-8
PG 5
ER
PT J
AU Das, RB
Bhaumik, S
Firoz, A
Mandsaurwala, A
Satam, H
AF Das, Ranjan Bibhu
Bhaumik, Sangeet
Firoz, Ahmad
Mandsaurwala, Aziz
Satam, Heena
TI Molecular Spectrum of Somatic EGFR and KRAS Gene Mutations in non Small Cell Lung Carcinoma: Determination of Frequency, Distribution Pattern and Identification of Novel Variations in Indian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR mutation; Lung cancer; Novel mutation; India
ID EGFR mutation; Lung cancer; Novel mutation; India
AB Somatic mutations of EGFR and KRAS gene represent the most common alterations currently known in NSCLC patients. This study explored the frequency, distribution pattern of EGFR and KRAS mutations in Indian patients. The frequencies of EGFR and KRAS mutations were 29 % (116/400) and 4.5 % (6/132) respectively. Both EGFR and KRAS mutations were prevalent in females, and a trend towards higher mutation frequency was seen in patients under≥ 60 years age. The presence of EGFR and KRAS mutations were higher in adenocarcinomas in comparison to other histological subtype. Sequencing analysis of EGFR exon 18 revealed Inframe deletion (G709_T710>A) and missense mutation (K713R). Among exon 19 positive cases, 49.3 % (37/75) were in-frame deletions, of which E746_A750del was frequent. Similarly, ~47 % (35/75) cases showed complex mutation involving indel. Among mutations in exon 20 (N= 9), 8 were substitutions, one showed duplication, while all exon 21 mutations were of the missense types with L858R as the most recurrent type. Sequencing analysis of KRAS exon 1 revealed three different types codon 12 substitutions resulting in c34G>T (G12C) (n=4), c.35G>A (G12D) (n=1), and c.35G>T (G12V) (n=1). In conclusion, the present study is an example of molecular diversity of EGFR and KRAS gene in Indian patients and further confirms that the frequency of EGFR and KRAS mutations varies considerably globally. To the best of our knowledge, this is the first Indian study to evaluate KRAS mutation. The current study also served to identify novel variations that added new insights into the genetic heterogeneity of NSCLC.
C1 [Das, Ranjan Bibhu] SRL Ltd, Research and Development, Plot No.1, Prime square building S.V.Road, Goregaon (W), 400062 Mumbai, India.
[Bhaumik, Sangeet] SRL Ltd, Research and Development, Plot No.1, Prime square building S.V.Road, Goregaon (W), 400062 Mumbai, India.
[Firoz, Ahmad] SRL Ltd, Research and Development, Plot No.1, Prime square building S.V.Road, Goregaon (W), 400062 Mumbai, India.
[Mandsaurwala, Aziz] SRL Ltd, Research and Development, Plot No.1, Prime square building S.V.Road, Goregaon (W), 400062 Mumbai, India.
[Satam, Heena] SRL Ltd, Research and Development, Plot No.1, Prime square building S.V.Road, Goregaon (W), 400062 Mumbai, India.
RP Das, RB (reprint author), SRL Ltd, Research and Development, 400062 Mumbai, India.
EM brdas@srl.in
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 675
EP 687
DI 10.1007/s12253-014-9874-7
PG 13
ER
PT J
AU Saadat, M
Pashaei, S
Amerizade, F
AF Saadat, Mostafa
Pashaei, Samira
Amerizade, Foroozan
TI Susceptibility to Gastric Cancer and Polymorphisms of Insertion/Deletion at the Intron 3 of the XRCC4 and VNTR at the Promoter Region of the XRCC5
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Polymorphism; Ins/Del; VNTR; XRCC4; XRCC5
ID Gastric cancer; Polymorphism; Ins/Del; VNTR; XRCC4; XRCC5
AB The genes encoding X-ray repair crosscomplementing group 4 (XRCC4; OMIM: 194363) and 5 (XRCC5; OMIM: 194364) are involved in repair of DNA double-strand breaks. To investigating the associations between polymorphisms of Insertion/Deletion (I/D, rs28360071) in the intron 3 of the XRCC4 and VNTR in the promoter region of the XRCC5 and risk of gastric cancer, the present study was carried out. We included 159 (56 females, 103 males) with gastric cancer and 242 (75 females, 167 males) healthy blood donors frequency matched for age and gender. Using PCR-basedmethods, the genotypes of the study polymorphisms were determined. The alleles of VNTR XRCC5 polymorphism divided into two groups: L (0 and 1 repeats) and H (2 and 3 repeats) alleles. For the I/D XRCC4 polymorphism, after stratification of the subjects according to their family history (FH) of cancer, either the ID (OR=3.19, 95%CI: 1.35–7.50, P=0.008) or the DD genotypes (OR= 4.62, 95%CI: 1.63–13.0, P=0.004) among positive FH persons, increased the risk of gastric cancer compared with the reference group (persons who have negative FH and II genotype). For the VNTR XRCC5 polymorphism, the LH+HH genotypes among positive FH persons, increased the risk of gastric cancer compared with the reference group (persons who have negative FH and LL genotype) (OR=2.88, 95%CI: 1.34–6.18, P=0.006). Sensitivity analysis showed that the above mentioned associations were not occurred due to the maldistribution of the genotypes among missing data. The present study suggests that both polymorphisms of the XRCC4 and XRCC5 might be risk factors for gastric cancer development especially among persons with positive FH.
C1 [Saadat, Mostafa] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
[Pashaei, Samira] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
[Amerizade, Foroozan] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
RP Saadat, M (reprint author), Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
EM saadat@shirazu.ac.ir;msaadat41@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 689
EP 693
DI 10.1007/s12253-014-9875-6
PG 5
ER
PT J
AU Wu, H
Sun, Y
Ye, H
Yang, Sh
Lee, LS
de las Morenas, A
AF Wu, Hao
Sun, Yue
Ye, Huihui
Yang, Shi
Lee, L Stephanie
de las Morenas, Antonio
TI Anaplastic Thyroid Cancer: Outcome and the Mutation/Expression Profiles of Potential Targets
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anaplastic thyroid cancer; Targeted therapy; PDL1; BRAF; c-KIT
ID Anaplastic thyroid cancer; Targeted therapy; PDL1; BRAF; c-KIT
AB Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the thyroid. No effective treatment modalities are currently available. Targeted therapy against protein kinases showed promising results in preclinical studies. Our goal was to assess the mutational status of potential therapeutic targets, as well as the biomarker for immunotherapy in the clinical context. Using allele specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1 in anaplastic thyroid cancer specimens. Results were compared to clinical information and patient outcome to assess the utility of these biomarkers. There were 13 patients in our study with a median overall survival of 19 weeks. Of the 13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1 expression was seen in 3 (23 %) patients, none of them were surgical candidates due to unresectability and poor performance status. KRAS codon 12/13 and EGFR exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase inhibitors and immunotherapy may be useful adjuvant therapies for ATC.
C1 [Wu, Hao] Baylor College of Medicine, Texas Children’s Hospital, Department of Pathology, AB190.11, 6621 Fannin Street, 77030 Houston, TX, USA.
[Sun, Yue] Boston University Medical Center, Department of Pathology and Laboratory Medicine, 02118 Boston, MA, USA.
[Ye, Huihui] Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Pathology and Laboratory Medicine, 02115 Boston, MA, USA.
[Yang, Shi] Boston University Medical Center, Department of Pathology and Laboratory Medicine, 02118 Boston, MA, USA.
[Lee, L Stephanie] Boston University Medical Center, Department of Medicine, 02118 Boston, MA, USA.
[de las Morenas, Antonio] Boston University Medical Center, Department of Pathology and Laboratory Medicine, 02118 Boston, MA, USA.
RP Wu, H (reprint author), Baylor College of Medicine, Texas Children’s Hospital, Department of Pathology, 77030 Houston, USA.
EM hao.wu@bcm.edu
CR Carling T, Udelsma R, 2008, Thyroid tumors. In: DeVita VT, Lawrence TS, Rosenberg SA, eds, Devita, Hellman & Rosenberg’s cancer [electronic resource]: principles and practice of oncology. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, pp 1663–1682
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Kimura H, Nakajima T, Takeuchi K et al, 2012, ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity. Lung Cancer 75:66–72
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 695
EP 701
DI 10.1007/s12253-014-9876-5
PG 7
ER
PT J
AU Nowakowski, A
de Souza, CS
Jach, R
Rosillon, D
Ksiazek, A
Holl, K
AF Nowakowski, Andrzej
de Souza, Collas Sabrina
Jach, Robert
Rosillon, Dominique
Ksiazek, Alicja
Holl, Katsiaryna
TI HPV-Type Distribution and Reproducibility of Histological Diagnosis in Cervical Neoplasia in Poland
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; CIN; Diagnosis reproducibility; HPV; Poland
ID Cervical cancer; CIN; Diagnosis reproducibility; HPV; Poland
AB This study was performed to assess attribution of high grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) to human papillomavirus (HPV) genotypes and secondarily to assess reproducibility of HG-CIN/ICC diagnosis obtained in Poland. Formaldehyde fixed, paraffin embedded blocks of HG-CIN/ICC from two distant institutions were sent to a central laboratory together with original histological diagnoses. Central/ expert review of histopathological specimens was performed and agreement between local and central/expert diagnoses was calculated. HPV detection and genotyping in the samples was carried out with the use of SPF10- LiPA25 technology. Results were analyzed for 205 HGCIN and 193 ICC cases with centrally confirmed diagnoses. Kappa coefficients and 95 % confidence intervals for HG-CIN and ICC diagnoses were: 0.13 (0.09;0.17) and 0.19 (0.11;0.26) respectively. Cohen’s kappa coefficients for lesions with representative number of samples ranged from 0.01 for cervical intraepithelial neoplasia grade 2 to 0.75 for adenocarcinoma. HPV DNA was detected in 96.1 and 91.2 % of the confirmed HG-CIN and ICC specimens respectively. HPV positive HG-CIN was most commonly attributed to HPV types: 16 (62.8), 33 (7.8), 31 (6.6), 52 (3.7), 45 (2.6) and 58 (2.6 %). HPV positive ICC was most commonly attributed to HPV types: 16 (72.1), 18 (10.8), 33 (5.7), 45 (3.4) and 31 (1.7 %). Reproducibility of histological diagnosis of HG-CIN/ICC obtained in Poland generally increases with the severity of lesion and is lowest for cervical intraepithelial neoplasia grade 2 and highest for adenocarcinoma. Over 80 % of ICC cases are vaccinepreventable in Poland.
C1 [Nowakowski, Andrzej] Medical University of Lublin, Department of Oncologic Gynecology and Gynecology, ul. Staszica 16, 20-081 Lublin, Poland.
[de Souza, Collas Sabrina] 4Clinics, 8 rue de la Terrasse, F-75017 Paris, France.
[Jach, Robert] Krakow University Hos, Medical College of Jagiellonian University, Department of Obstetrics and Perinatology, ul. Kopernika 23, 31-501 Krakow, Poland.
[Rosillon, Dominique] GlaxoSmithKline Vaccines, Rue Fleming 20, 1300 Wavre, Belgium.
[Ksiazek, Alicja] GlaxoSmithKline, ul. Rzymowskiego 53, 02-697 Warsaw, Poland.
[Holl, Katsiaryna] GlaxoSmithKline Vaccines, Rue Fleming 20, 1300 Wavre, Belgium.
RP Nowakowski, A (reprint author), Medical University of Lublin, Department of Oncologic Gynecology and Gynecology, 20-081 Lublin, Poland.
EM andrzejmnowakowski@poczta.onet.pl
CR Spaczynski M, Karowicz-Bilinska A, Rokita W et al, 2010, Attendance rate in the polish cervical cancer screening program in the years 2007–2009. Ginekol Pol 81:655–663
IARC. Globocan 2008, Section of Cancer Information. Available at: http://globocan.iarc.fr/factsheets/cancers/cervix.asp. Accessed on December 11, 2012.
Nowakowski A, Jackowska T, Oszukowski P, Radowicki S,Wysocki J, Zatonski W, 2013, Prevention of cervical cancer – an interdisciplinary problem. Can we improve the situation in Poland and how? Pediatr Pol 88:340–346
The communicate of Chief Sanitary Inspector for Poland on the Programme of Immunization for the year 2013. Available at: http:// dziennikmz.mz.gov.pl/DUM_MZ/2012/78/akt.pdfa
Kedzia W, Pruski D, Jozefiak A, Rokita W, Spaczynski M, 2010, Genotyping of oncogenic human papilloma viruses in women with HG SIL diagnosis. Ginekol Pol 81:740–744
Bardin A, Vaccarella S, Clifford GM et al, 2008, Human papillomavirus infection inwomen with and without cervical cancer inWarsaw, Poland. Eur J Cancer 44:557–564
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Klaes R, Benner A, Friedrich T et al, 2002, p16INK4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol 26:1389–1399
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Dijkstra MG, Heideman DA, de Roy SC et al, 2010, p16, INK4a, immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions. J Clin Pathol 63:972– 977
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 703
EP 711
DI 10.1007/s12253-014-9877-4
PG 9
ER
PT J
AU Oh, RH
An, HCh
Yoo, JN
Lee, HS
AF Oh, Rim Hye
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of MUC15 Gene in Gastric and its Regional Heterogeneity in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MUC15; MUC7; Heterogeneity; Mutation; Cancer; Microsatellite instability
ID MUC15; MUC7; Heterogeneity; Mutation; Cancer; Microsatellite instability
AB Mucins are important in tumorigenesis and expressional alterations of mucins are common in human cancers. A membrane-bound mucin MUC15 and secreted mucins MUC4 and MUC7 are known to involve in tumorigenesis, but their mutation status in cancers remains unknown. Aim of this study was to explore whether MUC4, MUC7 and MUC15 genes are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). In a public database, we found that MUC15 and MUC7 genes had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI). We analyzed the mutations in 90 GC and 141 CRC (high MSI (MSI-H) or stable MSI/low MSI (MSS/MSI-L)) by single-strand conformation polymorphism analysis and DNA sequencing. In the present study, we found MUC15 frameshift mutations (14.7% of GC and 15.2% of CRC with MSI-H), MUC 7 frameshift mutations (2.9% of GC with MSI-H) and MUC4 frameshift mutations (8.8% of GC and 3.8% of CRC with MSI-H). These mutations were not found in in MSS/MSI-L (0/118). Additionally, we analyzed intratumoral heterogeneity (ITH) of MUC15 mutation in 16 CRC and found that seven CRC (43.8%) harbored regional ITH of MUC15. We also analyzed MUC15 expression in GC and CRC by immunohistochemistry. Negative MUC15 expression was identified in 15–41% of the GC and CRC irrespective of MSI status. Of note, the negative expression was more common in those with MUC15 mutations.We identified alterations of MUC genes at various levels (frameshift mutations, genetic ITH and expression loss), which together might play a role in tumorigenesis of GC and CRC with MSI-H. Our data suggest that mutation analysis in multiple regions is needed for a better evaluation of mutation status in CRC with MSI-H.
C1 [Oh, Rim Hye] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General Surgery, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 713
EP 718
DI 10.1007/s12253-014-9878-3
PG 6
ER
PT J
AU Chen, G
Li, H
Niu, X
Li, G
Han, N
Li, X
Li, G
Liu, Y
Sun, G
Wang, Y
Li, Z
Li, Q
AF Chen, Guoting
Li, Hengping
Niu, Xianping
Li, Guofeng
Han, Ning
Li, Xin
Li, Guang
Liu, Yangzhou
Sun, Guixin
Wang, Yong
Li, Zengchun
Li, Qinchuan
TI Identification of Key Genes Associated with Colorectal Cancer Based on the Transcriptional Network
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Differentially expressed genes; Transcriptional network; Module selection; Functional analysis
ID Colorectal cancer; Differentially expressed genes; Transcriptional network; Module selection; Functional analysis
AB Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and adenoma vs. CRC, were identified using the Wilcoxon test method in R respectively. The interactive network of DEGs was constructed to select the significant modules using the Pearson’s correlation. Meanwhile, transcriptional network of DEGs was also constructed using the g: Profiler. Totally, 2, 741 DEGs in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs. CRC were identified. Moreover, function analysis of DEGs in each group showed FcR-mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in module 6, and Jak-STAT signaling pathway in module 19 were also enriched. Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT, SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development. Therapy targeting on the functions of these key genes might provide novel perspective for CRC treatment.
C1 [Chen, Guoting] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Hengping] Shandong Laigang Hoaspital, Department of General Surgery, 271126 Laiwu, Shandong Province, China.
[Niu, Xianping] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Guofeng] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Han, Ning] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Xin] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Guang] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Liu, Yangzhou] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Sun, Guixin] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Wang, Yong] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Zengchun] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
[Li, Qinchuan] Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, No. 150, Jimo Road, 200120 Shanghai, China.
RP Li, Q (reprint author), Tongji University School of Medicine, East Hospital, Department of Emergency Surgery, 200120 Shanghai, China.
EM li.qinchuan@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 719
EP 725
DI 10.1007/s12253-014-9880-9
PG 7
ER
PT J
AU Chen, B
Hu, KW
Zhang, JW
Wei, ZJ
Meng, XL
Xiong, MM
AF Chen, Bo
Hu, Kong-Wang
Zhang, Jia-Wei
Wei, Zhi-Jian
Meng, Xiang-Ling
Xiong, Mao-Ming
TI A critical Analysis of the Relationship Between Aldehyde dehydrogenases-2 Glu487Lys Polymorphism and Colorectal Cancer Susceptibility
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Aldehyde dehydrogenases-2; ALDH-2; Polymorphism; Risk factor
ID Colorectal cancer; Aldehyde dehydrogenases-2; ALDH-2; Polymorphism; Risk factor
AB Studies investigating the association between genetic polymorphism of aldehyde dehydrogenases-2 (ALDH- 2) Glu487Lys and colorectal cancer (CRC) risk have reported conflicting results. Given this uncertainty, we carried out a critical analysis of published case-control studies to derive a more precise estimation of this relationship. Published literature from PubMed, EMBASE and China Knowledge Resource Integrated Database were retrieved, and the literature search was updated in June 2014. Eleven studies comprising 6965 subjects were selected (2300 cases and 4665 controls). Overall, our study showed no statistical significance for CRC risk associated with any of the genetic models of ALDH-2 Glu487Lys polymorphism. When studies were stratified for control source, a decreased risk of CRC for participants with Lys/Lys was observed in population based case-control studies [Lys/Lys vs. (Glu/Lys + Glu/Glu): odds ratio (OR)=0.57, 95% confidence interval (CI)=0.38–0.87]. Furthermore, we also confirmed the significant correlation between Glu487Lys polymorphism and the influence on the risk of rectal cancer in males [Glu/Glu vs. (Glu/Lys + Lys/Lys): OR=1.52, 95%CI= 1.10–2.08]. The combined effects of the two gene polymorphisms [ALDH-2 and alcohol dehydrogenase 1B (ADH-1B)] were also studied. Compared with subjects having ALDH-2 Lys+ with ADH-1B His/His, ORs and 95%CIs for those with ALDH-2 Glu/Glu and ADH-1B His/His was 3.42(0.57– 20.38). Similar trends were observed for the other two types of comparisons. Our study supports that ALDH-2 Glu487Lys polymorphism is associated with significant reduced risks of CRC in population-based samples, and of rectal cancer in males.
C1 [Chen, Bo] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
[Hu, Kong-Wang] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
[Zhang, Jia-Wei] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
[Wei, Zhi-Jian] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
[Meng, Xiang-Ling] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
[Xiong, Mao-Ming] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, Anhui, China.
RP Xiong, MM (reprint author), The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
EM anyixmm@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 727
EP 733
DI 10.1007/s12253-014-9881-8
PG 7
ER
PT J
AU Isic Dencic, MT
Savin, BS
Selemetjev, AS
Paskas, DS
Zivaljevic, RV
Bozic, DV
Cvejic, SD
AF Isic Dencic, M Tijana
Savin, B Svetlana
Selemetjev, A Sonja
Paskas, D Svetlana
Zivaljevic, R Vladan
Bozic, D Vesna
Cvejic, S Dubravka
TI Strong Expression of HBME-1 Associates with High-Risk Clinicopathological Factors of Papillary Thyroid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid carcinoma; HBME-1; Diagnosis; Prognosis; Lymph node metastasis; pT; pTNM
ID Papillary thyroid carcinoma; HBME-1; Diagnosis; Prognosis; Lymph node metastasis; pT; pTNM
AB Thyroid cancer comprises a heterogeneous group of lesions with great diversity of biological behaviour. Markers which could help clinicians to identify high-risk patients for tailored optimization of clinical management are of crucial importance. HBME-1 protein level was analysed immunohistochemically using routinely prepared archival tissue sections of a broad range of papillary thyroid carcinoma (PTC) variants and in corresponding lymph node metastases (LNM). The results were evaluated in comparison with clinicopathological features of PTC. Positive immunoreaction was noticed in most classical (83/92; 90.2 %), follicular (60/71; 84.5 %) and trabecular (4/5; 80.0 %) variants of PTC. All cases of macrofollicular, Warthin-like and diffuse sclerosing PTC variants were HBME-1 positive (4/4, 3/3, 2/2; 100 % respectively). Tall cell and solid PTC variants showed diversity of staining (2/3; 66.67 % and 13/23; 56.52 % respectively), while PTCs with mixed histological pattern containing insular areas were mainly weakly positive (2/5; 40.0 %). A single case of clear cell PTC variant showed no reaction. Moreover, all matched metastatic PTC into lymph nodes (LNM) were HBME-1 positive (17/17; 100 %) and expressed HBME-1 in a similar pattern to the matched primary tumour. We also found a statistically significant association between high HBME-1 expression and the presence of lymph node metastasis, advanced pT status and pTNM stage (P<0.05), but only a tendency for association with extrathyroidal invasion of the tumour (P=0.058). Therefore, we recommend using immunoexpression of HBME-1 as useful mean to increase the likelihood of detecting most PTC variants and to predict some unfavourable clinical parameters in these patients.
C1 [Isic Dencic, M Tijana] University of Belgrade, Institute for the Application of Nuclear Energy - INEP, Banatska 31b, Zemun, 11080 Belgrade, Serbia.
[Savin, B Svetlana] University of Belgrade, Institute for the Application of Nuclear Energy - INEP, Banatska 31b, Zemun, 11080 Belgrade, Serbia.
[Selemetjev, A Sonja] University of Belgrade, Institute for the Application of Nuclear Energy - INEP, Banatska 31b, Zemun, 11080 Belgrade, Serbia.
[Paskas, D Svetlana] University of Belgrade, Institute for the Application of Nuclear Energy - INEP, Banatska 31b, Zemun, 11080 Belgrade, Serbia.
[Zivaljevic, R Vladan] Clinical Center of Serbia, Clinic of Endocrinology, Diabetes and Metabolic Diseases, 11000 Belgrade, Serbia.
[Bozic, D Vesna] University of Belgrade, Faculty of Medicine, Institute for Pathology, 11000 Belgrade, Serbia.
[Cvejic, S Dubravka] University of Belgrade, Institute for the Application of Nuclear Energy - INEP, Banatska 31b, Zemun, 11080 Belgrade, Serbia.
RP Isic Dencic, MT (reprint author), University of Belgrade, Institute for the Application of Nuclear Energy - INEP, 11080 Belgrade, Serbia.
EM tijana@inep.co.rs
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 735
EP 742
DI 10.1007/s12253-014-9883-6
PG 8
ER
PT J
AU Sumegi, K
Jaromi, L
Magyari, L
Kovesdi, E
Duga, B
Szalai, R
Maasz, A
Matyas, P
Janicsek, I
Melegh, B
AF Sumegi, Katalin
Jaromi, Luca
Magyari, Lili
Kovesdi, Erzsebet
Duga, Balazs
Szalai, Renata
Maasz, Anita
Matyas, Petra
Janicsek, Ingrid
Melegh, Bela
TI Functional Variants of Lipid Level Modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 Genes in Healthy Roma and Hungarian Populations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Polymorphisms; Triglyceride; Roma; Hungarian
ID Polymorphisms; Triglyceride; Roma; Hungarian
AB The role of triglyceride metabolism in different diseases, such as cardiovascular or cerebrovascular diseases is still under extensive investigations. In genome-wide studies several polymorphisms have been reported, which are highly associated with plasma lipid level changes. Our goal was to examine eight variants: rs12130333 at the ANGPTL3, rs16996148 at the CILP2, rs17321515 at the TRIB1, rs17145738 and rs3812316 of the MLXIPL, rs4846914 at GALNT2, rs1260326 and rs780094 residing at the GCKR loci. A total of 399 Roma (Gypsy) and 404 Hungarian population samples were genotyped using PCR-RFLP method. Significant differences were found between Roma and Hungarian population samples in both MLXIPL variants (C allele frequency of rs17145738: 94.1% vs. 85.6%, C allele frequency of rs3812316: 94.2% vs. 86.8% in Romas vs. in Hungarians, p<0.05), in ANGPTL3 (Tallele frequency of rs1213033: 12.2% vs. 18.5% in Romas vs. Hungarians, p<0.05) and GALNT2 (G allele frequency of rs4846914: 46.6% vs. 54.5% Romas vs. in Hungarians, p<0.05), while no differences over SNPs could be verified and the known minor alleles showed no correlation with triglyceride levels in any population samples. The current study revealed fundamental differences of known triglyceride modifying SNPs in Roma population. Failure of finding evidence for affected triglyceride metabolismshows that these susceptibility genes aremuch less effective compared for example to the apolipoprotein A5 gene.
C1 [Sumegi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Jaromi, Luca] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Magyari, Lili] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Kovesdi, Erzsebet] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Duga, Balazs] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Szalai, Renata] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Matyas, Petra] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Janicsek, Ingrid] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti u. 12, H-7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
EM melegh.bela@pte.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 743
EP 749
DI 10.1007/s12253-014-9884-5
PG 7
ER
PT J
AU Posfai,
Marton, I
Kiraly, AP
Kotosz, B
Kiss-Laszlo, Zs
Szell, M
Borbenyi, Z
AF Posfai, Eva
Marton, Imelda
Kiraly, Attila Peter
Kotosz, Balazs
Kiss-Laszlo, Zsuzsanna
Szell, Marta
Borbenyi, Zita
TI JAK2 V617F, MPL, and CALR Mutations in Essential Thrombocythaemia and Major Thrombotic Complications: A Single-Institute Retrospective Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myeloproliferative neoplasms; Essential thrombocythaemia; JAK2 V617F mutation; MPL mutations; CALR mutations; Thrombosis
ID Myeloproliferative neoplasms; Essential thrombocythaemia; JAK2 V617F mutation; MPL mutations; CALR mutations; Thrombosis
AB Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p=0.042), haemoglobin (p=0.000), red blood cell (p=0.000) and haematocrit (p=0.000) and hepatomegaly (p=0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395–4.258; p=0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.
C1 [Posfai, Eva] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Koranyi fasor 6, H-6720 Szeged, Hungary.
[Marton, Imelda] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Koranyi fasor 6, H-6720 Szeged, Hungary.
[Kiraly, Attila Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kotosz, Balazs] University of Szeged, Institute of Economics and Rural DevelopmentSzeged, Hungary.
[Kiss-Laszlo, Zsuzsanna] University of Szeged, Department of Medical GeneticsSzeged, Hungary.
[Szell, Marta] University of Szeged, Department of Medical GeneticsSzeged, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Koranyi fasor 6, H-6720 Szeged, Hungary.
RP Posfai, (reprint author), University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, H-6720 Szeged, Hungary.
EM evaposfay@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 751
EP 758
DI 10.1007/s12253-014-9885-4
PG 8
ER
PT J
AU Shinmura, K
Kato, H
Igarashi, H
Inoue, Y
Nakamura, S
Du, Ch
Kurachi, K
Nakamura, T
Ogawa, H
Tanahashi, M
Niwa, H
Sugimura, H
AF Shinmura, Kazuya
Kato, Hisami
Igarashi, Hisaki
Inoue, Yusuke
Nakamura, Satoki
Du, Chunping
Kurachi, Kiyotaka
Nakamura, Toshio
Ogawa, Hiroshi
Tanahashi, Masayuki
Niwa, Hiroshi
Sugimura, Haruhiko
TI CD44-SLC1A2 Fusion Transcripts in Primary Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD44-SLC1A2; Fusion transcript; Colorectal cancer
ID CD44-SLC1A2; Fusion transcript; Colorectal cancer
AB A CD44-SLC1A2 fusion has recently been discovered in a subset of primary gastric cancers, and an APIPSLC1A2 fusion has been described in a colon cancer cell line (SNU-C1); however, whether such SLC1A2 fusions occur in primary colorectal cancer (CRC) and whether such fusions are specific for gastrointestinal cancers remain uncertain. In the present study, we examined 90 primary CRCs and 112 primary non-small cell lung cancers (NSCLCs) for CD44-SLC1A2 and APIP-SLC1A2 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of both types of SLC1A2 fusion transcripts was not detected in any of the NSCLCs, the expression of CD44-SLC1A2, but not the APIP-SLC1A2 fusion transcript, was detected in one (1.1 %) CRC. The CD44-SLC1A2 fusion transcript was expressed in cancerous tissue but not in corresponding non-cancerous tissue, and the fusion occurred between exon 1 of CD44 and exon 2 of SLC1A2; it was expected that a slightly truncated but functional SLC1A2 protein would be produced under the CD44 promoter. A quantitative RT-PCR analysis revealed that SLC1A2 mRNA expression was upregulated in CRC containing SLC1A2 fusion transcripts, while it was downregulated in most other CRCs. The SLC1A2 fusion-positive carcinoma was located on the right-side of colon,was amucinous adenocarcinoma, was immunohistochemically negative for MSH2 mismatch repair protein, and contained no APC or KRAS mutations. Together, these results suggest that the expression of SLC1A2 fusion transcripts is related to a subset of primary CRCs and may contribute to the elucidation of the characteristics of SLC1A2 fusion-positive CRCs in the future.
C1 [Shinmura, Kazuya] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Kato, Hisami] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Igarashi, Hisaki] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Inoue, Yusuke] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Nakamura, Satoki] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Du, Chunping] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
[Kurachi, Kiyotaka] Hamamatsu University School of Medicine, Department of Surgery 2Hamamatsu, Japan.
[Nakamura, Toshio] Hamamatsu University School of Medicine, Department of Surgery 2Hamamatsu, Japan.
[Ogawa, Hiroshi] Seirei Mikatahara General Hospital, Division of PathologyHamamatsu, Japan.
[Tanahashi, Masayuki] Seirei Mikatahara General Hospital, Respiratory Disease Center, Division of Thoracic SurgeryHamamatsu, Japan.
[Niwa, Hiroshi] Seirei Mikatahara General Hospital, Respiratory Disease Center, Division of Thoracic SurgeryHamamatsu, Japan.
[Sugimura, Haruhiko] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Shizuoka, Japan.
RP Shinmura, K (reprint author), Hamamatsu University School of Medicine, Department of Tumor Pathology, 431-3192 Hamamatsu, Japan.
EM kzshinmu@hama-med.ac.jp
CR Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S,Watanabe H, Kurashina K, Hatanaka H, BandoM, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H, 2007, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448:561–566
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Shinmura K, Kageyama S, Tao H, Bunai T, Suzuki M, Kamo T, Takamochi K, Suzuki K, Tanahashi M, Niwa H, Ogawa H, Sugimura H, 2008, EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in nonsmall cell lung carcinomas. Lung Cancer 61:163–169
Matsuura S, Shinmura K, Kamo T, Igarashi H,Maruyama K, Tajima M, Ogawa H, Tanahashi M, Niwa H, Funai K, Kohno T, Suda T, Sugimura H, 2013, CD74-ROS1 fusion transcripts in resected nonsmall cell lung carcinoma. Oncol Rep 30:1675–1680
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 759
EP 764
DI 10.1007/s12253-014-9887-2
PG 6
ER
PT J
AU Naruse, T
Yanamoto, S
Yamada, Shi
Rokutanda, S
Kawakita, A
Kawasaki, G
Umeda, M
AF Naruse, Tomofumi
Yanamoto, Souichi
Yamada, Shin-ichi
Rokutanda, Satoshi
Kawakita, Akiko
Kawasaki, Goro
Umeda, Masahiro
TI Anti-Tumor Effect of the Mammalian Target of Rapamycin Inhibitor Everolimus in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral cancer; mTOR; Everolimus; Hypoxia
ID Oral cancer; mTOR; Everolimus; Hypoxia
AB The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC- 2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P<0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P<0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC.
C1 [Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yamada, Shin-ichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Rokutanda, Satoshi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawakita, Akiko] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawasaki, Goro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Naruse, T (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM naruse12@nagasaki-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 765
EP 773
DI 10.1007/s12253-014-9888-1
PG 9
ER
PT J
AU Vrdoljak, E
Geczi, L
Mardiak, J
Ciuleanu, TE
Leyman, S
Zhang, K
Sajben, P
Torday, L
AF Vrdoljak, Eduard
Geczi, Lajos
Mardiak, Jozef
Ciuleanu, Tudor-Eliade
Leyman, Sophie
Zhang, Ke
Sajben, Peter
Torday, Laszlo
TI Central and Eastern European Experience with Sunitinib in Metastatic Renal Cell Carcinoma: A Sub-analysis of the Global Expanded-Access Trial
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; Metastatic; Sunitinib; Expanded-access
ID Renal cell carcinoma; Metastatic; Sunitinib; Expanded-access
AB A global, open-label, expanded-access trial (EAT) provided sunitinib treatment on a compassionate-use basis to patients with metastatic renal cell carcinoma (mRCC) between 2005 and 2011. This retrospective analysis examines outcomes in patients from Central and East European (CEE) countries participating in the global EAT. Sunitinib (starting dose 50 mg orally once daily, with dose reduction for toxicity) was administered in repeated 6-week cycles (4 weeks on and 2 weeks off) until occurrence of disease progression or unacceptable toxicity. Tumor assessments were guided by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but were performed according to local standards of care. In total, 401 CEE patients received sunitinib (median treatment duration 9.6 months), of whom 378 were evaluable for tumor response. The most frequent grade ≥3 toxicities were fatigue (7.5 %), hypertension (7.0 %), thrombocytopenia (6.5 %), diarrhea (4.2 %), nausea and hand-foot syndrome (both 3.7 %) and neutropenia (3.0 %). Median overall survival was 30.7 months (95 % CI 23.3, months). Overall survival tended to be longer in cytokine-naive than cytokineexperienced patients (median 60.8 vs. 27.5 months; P= 0.1324). Among patients with evaluable tumors, 4.0 % achieved a complete and 14.6 % a partial response [objective response rate (ORR) 18.5 % (95 % CI 14.7, 22.8 %)].Median progression-free survival was 11.6 months (95 % CI 10.3, 12.8 months). Sunitinib demonstrates safety and effectiveness in real-world mRCC patients in CEE countries. Expandedaccess program patients showed a lower tumor response rate but similar survival outcomes to patients in the pivotal Phase III clinical trial of sunitinib in mRCC.
C1 [Vrdoljak, Eduard] University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, Spinciceva 1, 21000 Split, Croatia.
[Geczi, Lajos] National Institute of OncologyBudapest, Hungary.
[Mardiak, Jozef] National Cancer Institute, Department of Medical OncologyBratislava, Slovakia.
[Ciuleanu, Tudor-Eliade] University of Medicine and Pharmacy Iuliu Hatieganu, Institute of Oncology Ion ChiricutaCluj-Napoca, Romania.
[Leyman, Sophie] Pfizer Inc.Brussels, Belgium.
[Zhang, Ke] Pfizer Inc.La Jolla, CA, USA.
[Sajben, Peter] Pfizer Inc.New York, NY, USA.
[Torday, Laszlo] University of Szeged, Department of OncotherapySzeged, Hungary.
RP Vrdoljak, E (reprint author), University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, 21000 Split, Croatia.
EM edo.vrdoljak@gmail.com
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Moore LE, Hung R, Karami S, Boffetta P, Berndt S, Hsu CC, Zaridze D, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia- Dabrowska N, Mates D, Mukeria A, Holcatova I, Yeager M, Chanock S, Garcia-Closas M, Rothman N, Chow WH, Brennan P, 2008, Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer 122(8):1710–1715., DOI 10.1002/ ijc.23318
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 775
EP 782
DI 10.1007/s12253-014-9889-0
PG 8
ER
PT J
AU Imayama, N
Yamada, Shi
Yanamoto, S
Naruse, T
Matsushita, Y
Takahashi, H
Seki, S
Fujita, Sh
Ikeda, T
Umeda, M
AF Imayama, Naomi
Yamada, Shin-ichi
Yanamoto, Souichi
Naruse, Tomofumi
Matsushita, Yuki
Takahashi, Hidenori
Seki, Sachiko
Fujita, Shuichi
Ikeda, Tohru
Umeda, Masahiro
TI FOXC2 Expression is Associated with Tumor Proliferation and Invasion Potential in Oral Tongue Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FOXC2; Invasion; Metastasis; Proliferation; Oral tongue squamous cell carcinoma
ID FOXC2; Invasion; Metastasis; Proliferation; Oral tongue squamous cell carcinoma
AB Forkhead box protein C2 (FOXC2) is a gene encoding a transcription factor that controls the generation of mesodermal tissue including vascular and lymphatic tissues. FOXC2 has previously been associated with EMT and tumor angiogenesis in various cancers. Moreover, a relationship between the expression of FOXC2 and poor prognosis has been reported in various cancers.We herein examined the clinicopathological significance of FOXC2 in oral tongue squamous cell carcinoma (OTSCC) and attempted to clarify the function of FOXC2 in OTSCC cell lines in vitro. The overexpression of FOXC2 was more frequent in cancers with higher grades according to the pattern of invasion (grade 4 vs. 1–3; p<0.05).A correlationwas observed between the expression of FOXC2 and that of VEGF-A and -C (VEGF-A; p<0.05, VEGF-C; p<0.001). The high-FOXC2 expression group had a significantly poorer prognosis than that of the low-expression group (p<0.001). Multivariate analysis indicated that the overexpression of FOXC2 may also be an independent prognostic factor, similar to N classification (N0 vs 1/2; p<0.05), stage classification (stage I/II vs III/IV; p<0.05), pattern of invasion (grade 1-3vs 4; p<0.05), local recurrence (local recurrence (+) vs (−); p<0.01), and the overexpression of FOXC2 (FOXC2 overexpression (−) vs.(+); p<0.05). In the OTSCC cell line analysis, the expression of FOXC2 was also associated with proliferation and invasion potential. These results strongly suggest that the overexpression of FOXC2 may be a potent predictor of survival in OTSCC patients.
C1 [Imayama, Naomi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yamada, Shin-ichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Matsushita, Yuki] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Takahashi, Hidenori] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Seki, Sachiko] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
[Fujita, Shuichi] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
[Ikeda, Tohru] Nagasaki University Graduate School of Biomedical Sciences, Department of Oral Pathology and Bone MetabolismNagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Yamada, Shi (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM shinshin@nagasaki-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 783
EP 791
DI 10.1007/s12253-014-9891-6
PG 9
ER
PT J
AU Ahmed, AR
Aboelnaga, ME
AF Ahmed, Allah Rehab
Aboelnaga, M Engy
TI Thyroid Cancer in Egypt: Histopathological Criteria, Correlation With Survival and Oestrogen Receptor Protein Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid cancer; Immunohistochemistry; Papillary carcinoma; Oestrogen receptor; Egypt
ID Thyroid cancer; Immunohistochemistry; Papillary carcinoma; Oestrogen receptor; Egypt
AB Thyroid cancer represents approximately 1% of new cancer and oestrogen may play a role in the pathogenesis of thyroid neoplasm. We aimed to study the clinicopathological criteria and ER expression of thyroid cancer in Mansoura University (Egypt), and to correlate the survival to these clinicopathological data and ER expression. This retrospective study reviewed 644 patients with histologically proven thyroid carcinoma during the period from 2003 to 2011. 152 cases during the period between 2008 and 2011 were retrieved from the archive and examined by immunohistochemistry for oestrogen receptor-α (ER) expression. ER-α expression is significantly associated with the female sex, lymph node metastasis, TNM stage, extrathyroid extension, multifocality disease and recurrence and in the whole series (p<0.5). The same was noticed in papillary carcinoma (PTC) except the gender of the patient. Tumour type, extrathyroid extension and ER expression were the independent prognostic factors of DFS, while in PTC, only ER expression was the independent one. The histological type was the only independent prognostic factor for OAS in the series were studied for ER expression, while extrathyroid extension was the only one that affected OAS of PTC. There was significant positive correlation with lymph node metastasis and ER expression in whole patient and PTC cases. No difference in survival between the low and high ranges of positive oestrogen expression. The prognosis of thyroid carcinoma in Egypt is similar to that occurs worldwide. ER-α expression was a significant prognostic marker for DFS in thyroid cancer and can be used as a predictive factor of lymph node metastasis.
C1 [Ahmed, Allah Rehab] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Aboelnaga, M Engy] Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine DepartmentMansoura, Egypt.
RP Aboelnaga, ME (reprint author), Mansoura University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine Department, Mansoura, Egypt.
EM engyms2007@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 793
EP 802
DI 10.1007/s12253-014-9892-5
PG 10
ER
PT J
AU Alay, I
Turan, T
Ureyen, I
Karalok, A
Tasci, T
Ozfuttu, A
Kose, FM
Tulunay, G
AF Alay, Ismail
Turan, Taner
Ureyen, Isin
Karalok, Alper
Tasci, Tolga
Ozfuttu, Ahmet
Kose, Faruk Mehmet
Tulunay, Gokhan
TI Lymphadenectomy Should Be Performed Up to the Renal Vein in Patients with Intermediate-High Risk Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Supramesenteric lymph node; Lymphatic spread; Left renal vein
ID Endometrial cancer; Supramesenteric lymph node; Lymphatic spread; Left renal vein
AB We aimed to evaluate para-aortic metastases relative to the level of inferior mesenteric artery (IMA) and to discuss the clinico-pathological features of these patients. A total of 204 patients who underwent systematic pelvic and para-aortic lymphadenectomy up to the level of renal veins for endometrial cancer between January 2007 and August 2013 were included in this study. Of these 204 patients, 44 (21.6 %) had lymph node involvement. From a total of 27 patients with paraaortic lymph node (PALN) metastasis, 11 had only supramesenteric and 4 had only inframesenteric nodal involvement, while 12 had both supramesenteric and inframesenteric metastases. Supramesenteric lymph node metastases were detected in 85.2 % of patients who have paraaortic metastases and in 11.3 % of all patients. Additionally, 5 patients had only supramesenteric lymphatic metastasis. The surgico-pathological characteristics of patients with isolated supramesenteric and inframesenteric metastasis were similar. However, the patients with lymphatic spread in both regions were found to have pelvic lymphatic metastasis and cervical invasion more commonly compared to patients with only supramesenteric or only inframesenteric metastasis. The site of metastatic lymph nodes wasn’t associated with the likelihood and site of recurrence. Lymphadenectomy should be performed up to the level of renal vein in case of the presence of indication for lymphadenectomy in patients with endometrial cancer. Additionally, it is not possible to predict the patients with supramesenteric lymph node involvement by tumor grade, histological type and myometrial invasion.
C1 [Alay, Ismail] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Turan, Taner] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Ureyen, Isin] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Karalok, Alper] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Tasci, Tolga] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Ozfuttu, Ahmet] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Pathology Division, KeciorenAnkara, Turkey.
[Kose, Faruk Mehmet] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
[Tulunay, Gokhan] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Etlik Street, Kecioren, 06010 Ankara, Turkey.
RP Ureyen, I (reprint author), Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, 06010 Ankara, Turkey.
EM isin.ureyen@gmail.com
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ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK, 2009, Efficacy of systematic pelvic lymphadenectomy in endometrial cancer, MRC ASTEC trial): a randomized study. Lancet 373(9658):125–136
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Fotopoulou C, Savvatis K, Kraetschell R, Schefold JC, Lichtenegger W, Sehouli J, 2010, Systematic pelvic and aortic lymphadenectomy in intermediate and high-risk endometrial cancer: lymph-node mapping and identification of predictive factors for lymph-node status. Eur J Obstet Gynecol Reprod Biol 149(2):199–203
Kumar S, Podratz KC, Bakkum-Gamez JN et al, 2014, Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph nodemetastasis in endometrial cancer. Gynecol Oncol 132(1): 38–43
Nomura H, Aoki D, Suzuki N et al, 2006, Analysis of clinicopathologic factors predicting para-aortic lymph node metastasis in endometrial cancer. Int J Gynecol Cancer 16(2):799–804
Odagiri T,Watari H, Kato T, et al, 2014, Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials. Ann Surg Oncol
Chang SJ, Kim WY, Yoon JH, Yoo SC, Chang KH, Ryu HS, 2008, Para-aortic lymphadenectomy improves survival in patients with intermediate to high-risk endometrial carcinoma. Acta Obstet Gynecol Scand 87(12):1361–1369
Mariani A,Webb MJ, Galli L, Podratz KC, 2000, Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer. Gynecol Oncol 76(3):348–356
Todo Y, Kato H, Kaneuchi M, Watari H, Takeda M, Sakuragi N, 2010, Survival effect of para-aortic lymphadenectomy in endometrial cancer, SEPAL study): a retrospective cohort analysis. Lancet 375(9721):1165–1172
Meeting Report, 2009, The new FIGO staging system for cancers of the vulva, cervix, endometrium and sarcomas. Gynecol Oncol 115: 325–328
Turan T, Yilmaz SS, Hizli D et al, 2011, A prospective evaluation of lymphatic dissemination in endometrial cancer: is it adequate to perform lymph node dissection up to the inferior mesenteric artery? Int J Gynecol Cancer 21(5):864–869
Creutzberg CL, van Putten WL, Koper PC et al, 2000, Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomized trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 355(9213):1404–1411
National Comprehensive Cancer Network, 2014, Clinical practice guidelines in oncology, uterine cancers. Version 1. National Comprehensive Cancer Network, Washington, DC
Yokoyama Y, Maruyama H, Sato S et al, 1997, Indispensability of pelvic and paraaortic lymphadenectomy in endometrial cancers. Gynecol Oncol 64:411–417
Mariani A, Dowdy SC, Cliby WA et al, 2008, Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol 109:11– 18
Burke TW, Levenback C, Tornos C et al, 1996, Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer: results of a pilot study. Gynecol Oncol 62:169–173
Maccauro M, Lucignani G, Aliberti G et al, 2005, Sentinel lymph node detection following the hysteroscopic peritumoural injection of 99mTc-labelled albumin nanocolloid in endometrial cancer. Eur J Nucl Med Mol Imaging 32:569–574
Turan T, Hizli D, Sarici S et al, 2012, What is the impact of cervical invasion on lymph node metastasis in patients with stage IIIC endometrial cancer? Arch Gynecol Obstet 285(4):1119–1124
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 803
EP 810
DI 10.1007/s12253-014-9893-4
PG 8
ER
PT J
AU Berretta, R
Gizzo, S
Noventa, M
Marrazzo, V
Franchi, L
Migliavacca, C
Michela, M
Merisio, C
Modena, BA
Patrelli, ST
AF Berretta, Roberto
Gizzo, Salvatore
Noventa, Marco
Marrazzo, Vivienne
Franchi, Laura
Migliavacca, Costanza
Michela, Monica
Merisio, Carla
Modena, Bacchi Alberto
Patrelli, Silvio Tito
TI Quality of Life in Patients Affected by Endometrial Cancer: Comparison Among Laparotomy, Laparoscopy and Vaginal Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Laparotomic surgery; Laparoscopic surgery; Vaginal surgery; Quality of life; Complications
ID Endometrial cancer; Laparotomic surgery; Laparoscopic surgery; Vaginal surgery; Quality of life; Complications
AB The aim of this study is to verify if the surgical approach (laparoscopy/laparotomy/vaginal) in stage-I endometrial cancer treatment, may have effects on intra- and postoperative outcomes and on the patient’s quality of life. The study group consisted of patients with histological diagnosis of type-I endometrial adenocarcinoma, stage-I. They were divided into three groups according to surgical approach chosen (laparotomic/laparoscopic/vaginal). Every patient answered a telephone health survey (SF-36) at 30 and 180 days post-surgery. Surgical-operating times, hospitalization length and short/long-term complications after surgery were also compared. The SF-36 survey revealed a better performance status in patients who underwent laparoscopy as compared to those who received laparotomy or vaginal surgery. We found significantly better results considering General Health, Physical Functioning, Role-Physical and Bodily Pain in the laparoscopy group after 30 and 180 days. Patients who underwent laparoscopy had significantly shorter hospitalization and less post-operative complications even if laparoscopy required significantly longer surgical-operating times compared to vaginal surgery. Our data confirm the superiority of the laparoscopic approach respect to the laparotomic and vaginal ones both in term of hospitalization length and post-operative complications.
C1 [Berretta, Roberto] University of Parma, Department of Surgical SciencesParma, Italy.
[Gizzo, Salvatore] University of Padua, Department of Woman and Child Health, Via Giustiniani 3, 35128 Padova, Italy.
[Noventa, Marco] University of Padua, Department of Woman and Child Health, Via Giustiniani 3, 35128 Padova, Italy.
[Marrazzo, Vivienne] University of Parma, Department of Surgical SciencesParma, Italy.
[Franchi, Laura] University of Parma, Department of Surgical SciencesParma, Italy.
[Migliavacca, Costanza] University of Parma, Department of Surgical SciencesParma, Italy.
[Michela, Monica] University of Parma, Department of Surgical SciencesParma, Italy.
[Merisio, Carla] University of Parma, Department of Surgical SciencesParma, Italy.
[Modena, Bacchi Alberto] University of Parma, Department of Surgical SciencesParma, Italy.
[Patrelli, Silvio Tito] University of Parma, Department of Surgical SciencesParma, Italy.
RP Gizzo, S (reprint author), University of Padua, Department of Woman and Child Health, 35128 Padova, Italy.
EM ginecologia_padova@libero.it
CR Berretta R, Merisio C, Melpignano M et al, 2008, Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population. Int J Gynecol Cancer 18:797–802
Gizzo S, Di Gangi S, Bertocco A et al, 2014, Levonorgestrel intrauterine system in adjuvant tamoxifen treatment: balance of breast risks and endometrial benefits–systematic review of literature. Reprod Sci 21(4):423–431
Saccardi C, Gizzo S, Patrelli TS et al, 2013, Endometrial surveillance in tamoxifen users: role, timing and accuracy of hysteroscopic investigation: observational longitudinal cohort study. Endocr Relat Cancer 20(4):455–462
Patrelli TS, Berretta R, RollaMet al, 2009, Pelvic lymphadenectomy in endometrial cancer: our current experience. Eur J Gynaecol Oncol 30:536–538
Brazier JE, Harper R, Jones NM et al, 1992, Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ 305(6846):160–164
Pecorelli S, 2009, Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105:103–104
Mikuta JJ, 1993, International Federation of Gynecology and Obstetrics staging of endometrial cancer 1988. Cancer 71(4 Suppl): 1460–1463
Berretta R, Patrelli TS, Migliavacca C et al, 2014, Assessment of tumor size as a useful marker for the surgical staging of endometrial cancer. Oncol Rep 31(5):2407–2412
Gizzo S, Burul G, Di Gangi S et al, 2013, LigaSure vessel sealing system in vaginal hysterectomy: safety, efficacy and limitations.Arch Gynecol Obstet 288(5):1067–1074
Eltabbakh GH, 2002, Analysis of survival after laparoscopy in women with endometrial carcinoma. Cancer 95(9):1894–1901
Litta P, Fracas M, Pozzan C et al, 2003, Laparoscopicmanagement of early stage endometrial cancer. Eur J Gynaecol Oncol 24(1):41–44
Berretta R, Patrelli TS, Faioli R et al, 2013, Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature. Int J Clin Exp Pathol 6(8):1652–1657
Patrelli TS, Gizzo S, Di Gangi S et al, 2011, Cervical Mullerian adenosarcoma with heterologous sarcomatous overgrowth: a fourth case and review of literature. BMC Cancer 11:236
Patrelli TS, Silini EM, Gizzo S et al, 2011, Extragenital Mullerian adenosarcoma with pouch of Douglas location. BMC Cancer 11:171
Magrina JF, Weaver AL, 2004, Laparoscopic treatment of endometrial cancer: five-year recurrence and survival rates. Eur J Gynaecol Oncol 25(4):439–441
Malur S, Possover M,MichelsW, Schneider A, 2001, Laparoscopicassisted vaginal versus abdominal surgery in patients with endometrial cancer–a prospective randomized trial. Gynecol Oncol 80(2): 239–244
Holub Z, Jabor A, Bartos P et al, 2002, Laparoscopic surgery for endometrial cancer: long-term results of a multicentric study. Eur J Gynaecol Oncol 23(4):305–310
Zullo F, Palomba S, Russo T et al, 2005, A prospective randomized comparison between laparoscopic and laparotomic approaches in women with early stage endometrial cancer: a focus on the quality of life. Am J Obstet Gynecol 193(4):1344–1352
Nieboer TE, Hendriks JC, Bongers MY et al, 2012, Quality of life after laparoscopic and abdominal hysterectomy: a randomized controlled trial. Obstet Gynecol 119(1):85–91
Janda M, Gebski V, Brand A et al, 2010, Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer, LACE): a randomised trial. Lancet Oncol 11(8):772–780
Capelli G, De Vincenzo RI, Addamo A et al, 2002, Which dimensions of health-related quality of life are altered in patients attending the different gynecologic oncology health care settings? Cancer 95(12):2500–2507
Kornblith AB, Huang HQ, Walker JL et al, 2009, Quality of life of patients with endometrial cancer undergoing laparoscopic international federation of gynecology and obstetrics staging compared with laparotomy: a Gynecologic Oncology Group study. J Clin Oncol 27(32):5337–5342, Erratum in: J Clin Oncol. 2010 Jun 1;28(16): 2805
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 811
EP 816
DI 10.1007/s12253-014-9895-2
PG 6
ER
PT J
AU Terada, T
AF Terada, Tadashi
TI Expression of Cytokeratins in Glioblastoma Multiforme
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma multiforme; CK; Immunohistochemistry
ID Glioblastoma multiforme; CK; Immunohistochemistry
AB Little is known about the cytokeratin (CK) expressions in glioblastoma multiforme (GBM). The aim is to explore the CK expression in GM using immunohistochemistry (IHC). IHC study in 30 cases (median=68 years, SE=12.6) of GBM in brain. CK expression using AE1/3 antidody was seen in 29/30 (97 %) cases. There were no expressions of CK34BE12, CK5, CK6, CK7, CK8, CK14, CK 18, CK19, and CK20. Expression of p53 and glial fibrillary acidic protein (GFAP) were recognized in all 30 cases (100 %). All cases showed Ki-67 antigen labeling, index of which ranged from 6 to 43 % (m±SD=24+16). The IHC using CKAE1/3 in GBM very frequently shows positive reaction. The expression may cause difficulty in pathologic diagnosis in GBM, particularly in discrimination between GBM and metastatic carcinoma. The CK positivity in GM may be due to CK molecules other than CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19 and CK20. GBM frequently expression p53 and high Ki-67 labeling.
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, Miyakami 1231, Shimizu-Ku, 424-8636 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 424-8636 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
CR CosgroveM, Fitzgibbons PL, Sherrod A, Chandrasoma PT,Martin SE, 1989, Intermediate filament expression in astrocytic neoplasms.AmJ Surg Pathol 13:141–145
Ng HK, Lo ST, 1989, Cytokeratin immunoreactivity in gliomas. Histopathology 14:359–368
Cosgrove MM, Rich KA, Kunin SA, Sherrod AE, Martin SE, 1993, Keratin intermediate filament expression in astrocytic neoplasms: analysis by immunocytochemistry, western blot, and northern hybridization. Mod Pathol 6:342–347
Hirato J, Nakazato Y, Ogawa A, 1994, Expression of non-glial intermediate filament proteins in gliomas. Clin Neuropathol 13:1–11
Oh D, Prayson RA, 1999, Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study. Arch Pathol Lab Med 123:917–920
Goswami C, Chatterjee U, Sen S, Chatterjee S, Sarkar S, 2007, Expression of cytokeratins in gliomas. Indian J Pathol Microbiol 50: 478–481
Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y, 2002, Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746
Masica DL, Karchin R, 2011, Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival. Cancer Res 71:4550–4561
Jung TY, Jung S, Kim IY,Moon KS, JangWY, Park SJ, Kim YH, Kim HS, Min JJ, Kim J, 2012, Pathologic analysis of glioblastoma via multiple stereotactic biopsies of active tumor and necrosis. Oncol Rep 27:707–713
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 817
EP 819
DI 10.1007/s12253-015-9896-9
PG 3
ER
PT J
AU Marosvari, D
Teglasi, V
Csala, I
Marschalko, M
Bodor, Cs
Timar, B
Csomor, J
Harsing, J
Reiniger, L
AF Marosvari, Dora
Teglasi, Vanda
Csala, Iren
Marschalko, Marta
Bodor, Csaba
Timar, Botond
Csomor, Judit
Harsing, Judit
Reiniger, Lilla
TI Altered MicroRNA Expression in Folliculotropic and Transformed Mycosis Fungoides
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA; Mycosis fungoides; Folliculotropic mycosis fungoides; Transformed mycosis fungoides
ID MicroRNA; Mycosis fungoides; Folliculotropic mycosis fungoides; Transformed mycosis fungoides
AB Mycosis fungoides (MF) is a common, indolent primary cutaneous T-cell lymphoma (CTCL), with rare, more aggressive variants, such as folliculotropic MF (FMF). A minority of the MF cases may undergo large cell transformation (T-MF) associated with poor prognosis. A selection of microRNAs (miRs) contribute to the pathogenesis and progression of classic MF, and may also be useful in differential diagnostics. However, the molecular background of FMF and the mechanisms involved in large cell transformation are obscure. We analyzed the expression of 11 miRs in 9 FMF and 7 T-MF cases. Three miRs, including miR-93-5p, miR-181a and miR-34a were significantly upregulated in both FMF and T-MF. FMF also showed overexpression of miR-155 and miR-223, while miR-181b and miR-326 were overexpressed in T-MF cases compared to controls. These results by identifying a number of differentially expressed microRNAs add further insight into the molecular pathogenesis of folliculotropic MF and large cell transformation of MF.
C1 [Marosvari, Dora] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Teglasi, Vanda] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csala, Iren] Semmelweis University, Institute of Behavioural SciencesBudapest, Hungary.
[Marschalko, Marta] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Harsing, Judit] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Reiniger, Lilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Reiniger, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM lillareiniger@yahoo.com
CR Swerdlow SH, International Agency for Research on Cancer., World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: International Agency for Research on Cancer, 2008
Willemze R, Jaffe ES, Burg G et al, 2005)WHO-EORTC classification for cutaneous lymphomas. Blood 105:3768–85
Scarisbrick JJ, Kim YH,Whittaker SJ et al, 2014, Prognostic factors, prognostic indices and staging in mycosis fungoides and sezary syndrome: where are we now? Br J Dermatol 170:1226–36
Gerami P, Rosen S, Kuzel T, Boone SL, Guitart J, 2008, Folliculotropic mycosis fungoides: an aggressive variant of cutaneous T-cell lymphoma. Arch Dermatol 144:738–46
Vergier B, de Muret A, Beylot-Barry M et al, 2000, Transformation of mycosis fungoides: clinicopathological and prognostic features of 45 cases french study group of cutaneious lymphomas. Blood 95: 2212–8
BennerMF, Jansen PM,VermeerMH,Willemze R, 2012, Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 119:1643–9
Wong HK, Mishra A, Hake T, Porcu P, 2011, Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma, mycosis fungoides and Sezary syndrome). Br J Haematol 155:150–66
van Doorn R, Zoutman WH, Dijkman R et al, 2005, Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol 23:3886–96
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van Kester MS, Ballabio E, Benner MF et al, 2011, miRNA expression profiling of mycosis fungoides. Mol Oncol 5:273–80
Maj J, Jankowska-Konsur A, Sadakierska-Chudy A, Noga L, Reich A, 2011, Altered microRNA expression in mycosis fungoides. Br J Dermatol 166:331–6
Ralfkiaer U, Hagedorn PH, Bangsgaard N et al, 2011, Diagnostic microRNA profiling in cutaneous T-cell lymphoma, CTCL). Blood 118:5891–900
Moyal L, Barzilai A, Gorovitz B et al, 2013, miR-155 is involved in tumor progression of mycosis fungoides. Exp Dermatol 22:431–3
Contassot E, Kerl K, Roques S et al, 2008, Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression. Blood 111:4780–7
Dereure O, Levi E, Vonderheid EC, KadinME, 2002, Infrequent Fas mutations but no Bax or p53 mutations in early mycosis fungoides: a possible mechanism for the accumulation of malignant T lymphocytes in the skin. J Invest Dermatol 118:949–56
Wu J, Nihal M, Siddiqui J, Vonderheid EC, Wood GS, 2009, Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation. J Invest Dermatol 129:1165–73
Nielsen M, Kaestel CG, Eriksen KWet al, 1999, Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells. Leukemia 13:735–8
Sommer VH, Clemmensen OJ, Nielsen O et al, 2004, In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia 18:1288–95
Mao X, Orchard G, Lillington DM et al, 2004, BCL2 and JUNB abnormalities in primary cutaneous lymphomas. Br J Dermatol 151: 546–56
Mao X, Orchard G, Mitchell TJ et al, 2008, A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS. J Cutan Pathol 35:899–910
Mao X, Lillington D, Scarisbrick JJ et al, 2002, Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in sezary syndrome and mycosis fungoides. Br J Dermatol 147:464–75
Benner MF, Ballabio E, van Kester MS et al, 2012, Primary cutaneous anaplastic large cell lymphoma shows a distinct miRNA expression profile and reveals differences from tumor-stage mycosis fungoides. Exp Dermatol 21:632–4
Prochazkova M, Chevret E, Mainhaguiet G et al, 2007, Common chromosomal abnormalities in mycosis fungoides transformation. Genes, Chromosom Cancer 46:828–38
Laharanne E, Chevret E, Idrissi Y et al, 2010, CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma. Mod Pathol 23:547–58
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McGirt LY, Adams CM, Baerenwald DA, Zwerner JP, Zic JA, Eischen CM, 2013, miR-223 regulates cell growth and targets proto-oncogenes in mycosis fungoides/cutaneous T-cell lymphoma. J Investi Dermatol 134:1101–7
Mi QS, Xu YP,Wang H, Qi RQ, Dong Z, Zhou L, 2013, Deletion of microRNA miR-223 increases Langerhans cell cross-presentation. Int J Biochem Cell Biol 45:395–400
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Salgado R, Servitje O, Gallardo F et al, 2010, Oligonucleotide array- CGH identifies genomic subgroups and prognosticmarkers for tumor stage mycosis fungoides. J invest Dermatol 130:1126–35
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Scarisbrick JJ, Woolford AJ, Russell-Jones R, Whittaker SJ, 2000, Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN. Blood 95:2937–42
Katona TM, Smoller BR,Webb AL, Hattab EM, Khalil A, Hiatt KM, 2013, Expression of PTEN in mycosis fungoides and correlation with loss of heterozygosity. Am J Dermatopathol 35:555–60
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 821
EP 825
DI 10.1007/s12253-015-9897-8
PG 5
ER
PT J
AU Ivanov, BI
Gritsenko, AV
Miroshnikov, AS
AF Ivanov, B Iuri
Gritsenko, A Viktor
Miroshnikov, A Sergey
TI Evaluation of Antitumor Activity of Platelet Microbicidal Protein on the Model of Transplanted Breast Cancer in CBRB-Rb(8.17) 1Iem Mice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Platelet microbicidal protein; Antitumor activity; Breast cancer; Mouse model
ID Platelet microbicidal protein; Antitumor activity; Breast cancer; Mouse model
AB Breast cancer is the most common women’s cancer in the world. There is considerable current interest in developing anticancer agents with a new mode of action because of the development of resistance by cancer cells towards current anticancer drugs. Mamalian cells have been shown to contain small, cationic, microbicidal peptides. Antimicrobial peptides have drawn attention as a promising alternative to current antitumor agents. Such peptides have been isolated both from animal and human platelets and have been termed platelets microbicidal proteins (PMP). The aim of this work was to study antitumor activity of PMP in vivo on the model of mouse breast cancer in comparison with antitumor hexapeptide Arg-alpha-Asp-Lys-Val-Tyr-Arg (Immunofan). We demonstrated that the tumors treated with PMP were significant smaller than the control groups (P<0.05). In experiments in vivo using CBRB-Rb(8.17)1Iem mice with transplanted tumors PMP inhibited tumor growth during the treatments and after its discontinuation. These findings indicate that PMP can exert antitumor effects. Therefore, PMP may be used for the development of therapy for the intervention of breast cancer.
C1 [Ivanov, B Iuri] Russian Academy of Sciences, Institute of Cellular and Intracellular SymbiosisOrenburg, Russian Federation.
[Gritsenko, A Viktor] Russian Academy of Sciences, Institute of Cellular and Intracellular SymbiosisOrenburg, Russian Federation.
[Miroshnikov, A Sergey] Russian Academy of Agricultural Sciences, All-Russian Institute of Meat Cattle BreedingOrenburg, Russian Federation.
RP Ivanov, BI (reprint author), Russian Academy of Sciences, Institute of Cellular and Intracellular Symbiosis, Orenburg, Russian Federation.
EM ubi2010@rambler.ru
CR Biersack B, Ahmad A, Sarkar FH, Schobert R, 2012, Coinage metal complexes against breast cancer. Curr Med Chem 19:3949–3956
Trape AP, Gonzalez-Angulo AM, 2012, Breast cancer and metastasis: on the way toward individualized therapy. Cancer Genomics Proteomics 9:297–310
Caffarel MM, Andradas C, Perez-Gomez E, Guzman M, Sanchez C, 2012, Cannabinoids: a new hope for breast cancer therapy? Cancer Treat Rev 38:911–918
Hou L, Zhao X, Wang P, Ning Q, Meng M, Caigang L, 2013, Antitumor activity of antimicrobial peptides containing CisoDGRC in CD13 negative breast cancer cells. PLoS ONE 8:e53491., DOI 10. 1371/journal.pone.0053491
Shamova OV, Sakuta GA, Orlov DS, Zenin VV, Shteĭn GI,Kolodkin NI, Afonina IV, Kokriakov VN, 2007, Effects of antimicrobial peptides of neutrophils on tumor and normal cells in culture. Tsitologiia 49:1000–1010
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 827
EP 830
DI 10.1007/s12253-014-9812-8
PG 4
ER
PT J
AU Ata, A
Polat, A
Serinsoz, E
Sungur, AM
Arican, A
AF Ata, Alper
Polat, Ayse
Serinsoz, Ebru
Sungur, Ali Mehmet
Arican, Ali
TI Prognostic Value of Increased her2 Expression in Cancers of Pancreas and Biliary Tree
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER2; Cancers of pancreas and biliary tract; Survival
ID HER2; Cancers of pancreas and biliary tract; Survival
AB Increased HER2 expression has a prognostic, and predictive value in many solid cancer types, predominantly in breast cancer. However the effects of HER2 on survival from cancers of pancreas, gall bladder, cholangiocellular, and ampullary region are not known. In this study, the effects of increased HER2 expression on these types of cancer have been analyzed. Immunohistochemical HER2 staining was performed in 31 (44.9 %) female, and 38 (55.1 %) male patients with a mean age of 65±10 years, and various parameters, mostly survival rates of patients with pancreas (n=30; 43.5 %), gall bladder (n=17; 24.6 %), cholangiocellular (n= 12; 17.4%), and ampullary region (n=10; 14.5 %) carcinomas were evaluated. Strong (3 +) membranous staining for HER2 was observed in 2 patients with gall bladder cancers (11.76 % of all gall bladder cancers). In 2.90 % of all cases strong membranous staining (2+ or 3+) was observed. Weak (1+) membranous staining was noted in one (3.33 %) pancreatic, and one cholangiocellular (8.33 %) cancer patient, and in none of the ampullary region patient membranous staining for HER2 was observed. Since only scarce number of patients demonstrated membranous staining for HER2, survival analysis was not performed on these patients. Based on cytoplasmic HER2 staining scores, the patients were divided into weakly (0–3 pts; n=17 patients; 24.66 %), moderate (4–5 pts; n=22; 31.88 %), and strongly (6–7 pts; n=30; 43.46 %) stained groups. Patients whose specimens demonstrated borderline statistical significant (p=0.052) low staining for HER2 had higher survival rates when compared with other cases. Increased HER2 expression has no prognostic, and predictive value in cancers of pancreas, biliary tract, and ampulla vateri. If HER2 will be evaluated in these types of cancer, membranous, as well as cytoplasmic staining properties should be taken into account.
C1 [Ata, Alper] Mersin University School of Medicine, Department of Medical OncologyMersin, Turkey.
[Polat, Ayse] Mersin University School of Medicine, Department of PathologyMersin, Turkey.
[Serinsoz, Ebru] Mersin University School of Medicine, Department of PathologyMersin, Turkey.
[Sungur, Ali Mehmet] Mersin University School of Medicine, Department of BiostatisticsMersin, Turkey.
[Arican, Ali] Mersin University School of Medicine, Department of Medical OncologyMersin, Turkey.
RP Ata, A (reprint author), Mersin University School of Medicine, Department of Medical Oncology, Mersin, Turkey.
EM dralperata@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 831
EP 838
DI 10.1007/s12253-014-9847-x
PG 8
ER
PT J
AU Hata, N
Suzuki, OS
Murata, H
Hatae, R
Akagi, Y
Sangatsuda, Y
Amano, T
Yoshimoto, K
Tahira, T
Mizoguchi, M
AF Hata, Nobuhiro
Suzuki, O Satoshi
Murata, Hideki
Hatae, Ryusuke
Akagi, Yojiro
Sangatsuda, Yuhei
Amano, Toshiyuki
Yoshimoto, Koji
Tahira, Tomoko
Mizoguchi, Masahiro
TI Genetic Analysis of a Case of Glioblastoma with Oligodendroglial Component Arising During the Progression of Diffuse Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GBMO; IDH1; Loss of heterozygosity; Secondary glioblastoma
ID GBMO; IDH1; Loss of heterozygosity; Secondary glioblastoma
AB The most recent definition of glioblastoma with oligodendroglioma component (GBMO) assigned clinical significance to the observation of oligodendroglial foci within glioblastomas. However, the pathological mechanism of its histogenesis has not yet been determined. We report the genetic analysis of a GBMO case that evolved from an astrocyte lineage. A 37-year-old male underwent a third craniotomy for the removal of recurrent lesions of a secondary glioblastoma originating from a previous diffuse astrocytoma. The lesion in the right frontal lobe contained oligodendroglial foci within a glioblastoma background, while the remaining lesions showed only classic glioblastoma histology. Genetic analyses revealed distal 10q loss of heterozygosity (LOH) occurring de novo in the oligodendroglial tissue, as well as 10p, 17p LOH, and isocitrate dehydrogenase-1 gene (IDH1) mutations inherited from the previous lesions. The final recurrent glioblastoma underwent LOH on almost the entire of chromosome 10. Based on these results, the importance of an oligodendroglial component in glioblastomas may be limited.
C1 [Hata, Nobuhiro] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Suzuki, O Satoshi] Kyushu University, Graduate School of Medical Sciences, Department of NeuropathologyFukuoka, Japan.
[Murata, Hideki] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Hatae, Ryusuke] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Akagi, Yojiro] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Sangatsuda, Yuhei] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Amano, Toshiyuki] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Yoshimoto, Koji] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
[Tahira, Tomoko] Kyushu University, Medical Institute of Bioregulation, Division of Genome Analysis, Research Center for Genetic Information, 3-1-1 Maidashi, Higashi-kuFukuoka, Japan.
[Mizoguchi, Masahiro] Kyushu University, Graduate School of Medical Sciences, Department of NeurosurgeryFukuoka, Japan.
RP Hata, N (reprint author), Kyushu University, Graduate School of Medical Sciences, Department of Neurosurgery, Fukuoka, Japan.
EM hatanobu@kyumed.jp
CR Louis DN, Ohgaki H,Wiestler OD, CaveneeWK(eds,, 2007)World health organization classification of tumours of the central nervous system. IARC Press, Lyon
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SalvatiM, Formichella AI, D’EliaA, Brogna C, Frati A, Giangaspero F, Delfini R, Santoro A, 2009, Cerebral glioblastoma with oligodendrogliomal component: analysis of 36 cases. J Neuro- Oncol 94:129–134
Cairncross JG, Ueki K, Zlatescu MC et al, 1998, Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479
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Kraus JA, Lamszus K, Glesmann N et al, 2001, Molecular genetic alterations in glioblastomas with oligodendroglial component. Acta Neuropathol 101:311–320
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Sasaki H, Betensky RA, Cairncross JG, Louis DN, 2002, DMBT1 polymorphisms: relationship to malignant glioma tumorigenesis. Cancer Res 62:1790–1796
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 839
EP 843
DI 10.1007/s12253-014-9850-2
PG 5
ER
PT J
AU Jargin, VS
AF Jargin, V Sergei
TI Renal Cell Carcinoma after Chernobyl: on the Role of Radiation vs. Late Detection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jargin, V Sergei] Peoples’ Friendship University of Russia, Clementovski per 6-82, 115184 Moscow, Russian Federation.
RP Jargin, VS (reprint author), Peoples’ Friendship University of Russia, 115184 Moscow, Russian Federation.
EM sjargin@mail.ru
CR UNSCEAR, 2008, Report to the General Assembly. Sources and effects of ionizing radiation. Annex D. Health effects due to radiation from the Chernobyl accident. New York, United Nations
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Mould RF, 2000, The Chernobyl record. The definite history of Chernobyl catastrophe. Institute of Physics, Bristol & Philadelphia
Romanenko AM, Ruiz-Sauri A, Morell-Quadreny L, Valencia G, Vozianov AF, Llombart-Bosch A, 2012, Microvessel Density is High in Clear-Cell Renal Cell Carcinomas of Ukrainian Patients Exposed to Chronic Persistent Low-Dose Ionizing Radiation After the Chernobyl Accident. Virchows Arch 460:611–619., DOI 10.1007/ s00428–012–1243-x
Romanenko A, Morell-Quadreny L, Ramos D, Nepomnyaschiy V, Vozianov A, Llombart-Bosch A, 2006, Extracellular Matrix Alterations in Conventional Renal Cell Carcinomas by Tissue Microarray Profiling Influenced by the Persistent, Long-Term, low- Dose Ionizing Radiation Exposure in Humans. Virchows Arch 448: 584–590., DOI 10.1007/s00428–006–0160–2
Romanenko A, Morell-Quadreny L, Nepomnyaschy V, Vozianov A, Llombart-Bosch A, 2000, Pathology and Proliferative Activity of Renal-Cell Carcinomas, RCCS, and Renal Oncocytomas in Patients With Different Radiation Exposure After the Chernobyl Accident in Ukraine. Int J Cancer 87:880–883., DOI 10.1002/1097– 0215(20000915)87:6<880::AID-IJC19>3.0.CO;2-J
Romanenko A, Morell-Quadreny L, Nepomnyaschy V, Vozianov A, Llombart-Bosch A, 2001, Radiation Sclerosing Proliferative Atypical Nephropathy of Peritumoral Tissue of Renal-Cell Carcinomas After the Chernobyl Accident in Ukraine. Virchows Arch 438:146–153., DOI 10.1007/s004280000334
Morell-Quadreny L, Romanenko A, Lopez-Guerrero JA, Calabuig S, Vozianov A, Llombart-Bosch A, 2011, Alterations of Ubiquitylation and Sumoylation in Conventional Renal Cell Carcinomas After the Chernobyl Accident: a Comparison with Spanish Cases. Virchows Arch 459:307–313., DOI 10.1007/s00428–011–1124–8
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Jargin SV, 2007, Over-Estimation of Radiation-InducedMalignancy After the Chernobyl Accident. Virchows Arch 451:105–106., DOI 10. 1007/s00428–007–0428–1
Jargin SV, 2010, Chernobyl-Related Cancer: Re-Evaluation Needed. Turkish J Pathol 26:177–1., DOI 10.5146/tjpath.2010.01021
Romanenko A, Morell-Quadreny L, Ramos D, Nepomnyaschiy V, Vozianov A, Llombart-Bosch A, 2007, Author Reply to: Over-Estimation of Radiation-Induced Malignancy after the Chernobyl Accident. Virchows Arch 451:107–108., DOI 10. 1007/s00428–007–0442–3
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 845
EP 846
DI 10.1007/s12253-014-9787-5
PG 2
ER
PT J
AU Lee, HS
Je, ME
Yoo, JN
Lee, HS
AF Lee, Hak Sung
Je, Mi Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI HMCN1, a cell polarity-related gene, is somatically mutated in gastric and colorectal cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Lee, Hak Sung] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong Socho-gu, 137-701 Seoul, South Korea.
[Je, Mi Eun] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Vogel BE, Muriel JM, Dong C, Xu X, 2006, Hemicentins: what have we learned from worms? Cell Res 16:872–878
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Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–1047
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of theKEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 847
EP 848
DI 10.1007/s12253-014-9809-3
PG 2
ER
PT J
AU Oh, RH
An, HCh
Yoo, JN
Lee, HS
AF Oh, Rim Hye
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of TAF7L Gene, a Core Component for Transcription by RNA Polymerase II, in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Oh, Rim Hye] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General SurgerySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Gegonne A, Devaiah BN, Singer DS, 2013, TAF7: traffic controller in transcription initiation. Transcription 4:29–33
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Yazarloo F, Shirkoohi R, Mobasheri MB, Emami A, Modarressi MH, 2013, Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a genderdependent expression pattern. Med Oncol 30:368
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
YooNJ, KimHR, KimYR, An CH, Lee SH, 2012, Somaticmutations of the KEAP1 gene in common solid cancers. Histopathology 60:943– 952
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 849
EP 850
DI 10.1007/s12253-014-9832-4
PG 2
ER
PT J
AU Choi, JY
Yoo, JN
Lee, HS
AF Choi, Jin Youn
Yoo, Jin Nam
Lee, Hyung Sug
TI Mutation of HELLS, a Chromatin Remodeling Gene, Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Becker PB, 2002, HorzW(2002, ATP-dependent nucleosome remodeling. Annu Rev Biochem 71:247–273
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Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
YooNJ, KimHR, KimYR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Lee DW, Zhang K, Ning ZQ, Raabe EH, Tintner S, Wieland R, Wilkins BJ, Kim JM, Blough RI, Arceci RJ, 2000, Proliferationassociated SNF2-like gene, PASG): a SNF2 family member altered in leukemia. Cancer Res 60:3612–3622
GoelA, ArnoldCN,NiedzwieckiD,Carethers JM,Dowell JM,Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR, 2004, Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res 64:3014–3021
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 851
EP 852
DI 10.1007/s12253-014-9862-y
PG 2
ER
PT J
AU Choi, RM
Yoo, JN
Lee, HS
An, HCh
AF Choi, Ryoung Mi
Yoo, Jin Nam
Lee, Hyung Sug
An, Hyeok Chang
TI Frameshift Mutation of an Angiogenesis Factor VEGFB and its Mutational Heterogeneity in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Ryoung Mi] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General Surgery, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP An, HCh (reprint author), The Catholic University of Korea, College of Medicine, Department of General Surgery, 137-701 Seoul, South Korea.
EM achcolo@catholic.ac.kr
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Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U, 1996, Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci U S A 93:2576–2581
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Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Gylfe AE, Kondelin J, Turunen M, Ristolainen H, Katainen R, Pitkanen E, Kaasinen E, Rantanen V, Tanskanen T, Varjosalo M, Lehtonen H, Palin K, Taipale M, Taipale J, Renkonen-Sinisalo L, Jarvinen H, Bohm J, Mecklin JP, Ristimaki A, Kilpivaara O, Tuupanen S, Karhu A, Vahteristo P, Aaltonen LA, 2013, Identification of candidate oncogenes in human colorectal cancers with microsatellite instability. Gastroenterology 145(3):540–543
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
Calin GA, Gafa R, TibilettiMG, Herlea V, Becheanu G, Cavazzini L, Barbanti-Brodano G, Nenci I, Negrini M, Lanza G, 2000, Genetic progression in microsatellite instability high, MSI-H, colon cancers correlates with clinico-pathological parameters: a study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes. Int J Cancer 89:230–235
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 853
EP 855
DI 10.1007/s12253-015-9900-4
PG 3
ER
PT J
AU Choi, JY
Yoo, JN
Lee, HS
AF Choi, Jin Youn
Yoo, Jin Nam
Lee, Hyung Sug
TI Mutation and Expression of a Methyl-Binding Protein 6 (MBD6) in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR WeberM, Schubeler D, 2007, Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol 19: 273–280
SuzukiMM, Bird A, 2008, DNAmethylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476
Jung JS, Jee MK, Cho HT, Choi JI, Im YB, Kwon OH, Kang SK, 2013, MBD6 is a direct target of Oct4 and controls the stemness and differentiation of adipose tissue-derived stem cells. Cell Mol Life Sci 70:711–728
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
YooNJ, KimHR, KimYR, An CH, Lee SH, 2012, Somaticmutations of the KEAP1 gene in common solid cancers. Histopathology 60:943– 952
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 857
EP 858
DI 10.1007/s12253-015-9904-0
PG 2
ER
PT J
AU Je, ME
An, HCh
Chung, JY
Yoo, JN
Lee, HS
AF Je, Mi Eun
An, Hyeok Chang
Chung, Jun Yeun
Yoo, Jin Nam
Lee, Hyung Sug
TI GNAS Mutation Affecting Codon 201 is Rare in Most Human Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE GNAS; Mutation; Cancers
ID GNAS; Mutation; Cancers
C1 [Je, Mi Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General Surgery, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Chung, Jun Yeun] The Catholic University of Korea, College of Medicine, Department of Microbiology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L, 1989, GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340:692–696
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Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE, 2006, The consensus coding sequences of human breast and colorectal cancers. Science 314:268–274
Nishikawa G, Sekine S, Ogawa R, Matsubara A, Mori T, Taniguchi H, Kushima R, Hiraoka N, Tsuta K, Tsuda H, Kanai Y, 2013, Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. Br J Cancer 108:951–958
Nault JC, FabreM, Couchy G, Pilati C, Jeannot E, Tran Van Nhieu J, Saint-Paul MC, De Muret A, Redon MJ, Buffet C, Salenave S, Balabaud C, Prevot S, Labrune P, Bioulac-Sage P, Scoazec JY, Chanson P, Zucman-Rossi J, 2012, GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation. J Hepatol 56:184–191
Kalfa N, Lumbroso S, Boulle N, Guiter J, Soustelle L, Costa P, Chapuis H, Baldet P, Sultan C, 2006, Activating mutations of Gsalpha in kidney cancer. J Urol 176:891–895
Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, Shibata N, Shimizu K, Kamatani N, Shiratori K, 2011, Wholeexome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep 1:161
Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia- Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL, 2011, Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 364:2496–2506
Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson JR, Allen GE, Ng CC, Wong BH, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang D, Ong P, Chan-on W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema K, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S, Tan P, Teh BT, 2012, Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet 44:690–693
Jung SW, Lee SY, JekarlDW, KimM, LimJ, KimY, Han K, KimYJ, Cho SG, Song J, 2011, Cytogenetic characteristics and prognosis analysis in 231 myelodysplastic syndrome patients from a single institution. Leuk Res 35:735–740
Lee SH, Jeong EG, Soung YH, Lee JW, Yoo NJ, Lee SH, 2008, Absence of GNAS and EGFL6 mutations in common human cancers. Pathology 40:95–97
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2015
VL 21
IS 3
BP 859
EP 860
DI 10.1007/s12253-015-9919-6
PG 2
ER
PT J
AU Cserni, G
Maraz, R
AF Cserni, Gabor
Maraz, Robert
TI Regional Disease Control in Selected Patients with Sentinel Lymph Node Involvement and Omission of Axillary Lymph Node Dissection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Axillary lymph node dissection; Sentinel lymph node; Micrometastasis; Isolated tumour cells/clusters; Follow-up
ID Axillary lymph node dissection; Sentinel lymph node; Micrometastasis; Isolated tumour cells/clusters; Follow-up
AB Whether an axillary lymph node dissection (ALND) is needed for breast cancer patients with minimal sentinel lymph node (SLN) involvement is arguable despite recent data supporting the omission of axillary clearance in these patients. Data on disease recurrence of 111 patients with SLN involvement and no ALND were analysed. Patients with minimal SLN involvement were assessed for their risk of non- SLN metastasis by means of several nomograms. The series included patients with isolated tumour cells (n=76), micrmetastasis (n=33) and macrometastasis (n=2) who were followed for a median of 37 months (range 12–148 months). Six patients died, 3 of disease and 3 of unrelated causes. Eight further patients had breast cancer related events: 1 local breast recurrence and seven distant metastases. No axillary regional recurrence was detected. Disease related events were not associated with the risk of non-SLN metastasis. The presented data suggest that omitting ALND in patients with low volume SLN metastasis may be a safe procedure, and support the observation that systemic disease recurrence may not be associated with axillary recurrence or the risk of NSLN involvement predicted by nomograms.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Maraz, Robert] Bacs-Kiskun County Hospital, Department of Surgery, Nyiri ut 38, H-6000 Kecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V et al, 2010, Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg 251:595–600
Zavagno G, De Salvo GL, Scalco G, Bozza F, Barutta L, Del Bianco P et al, 2008, A randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the Sentinella/GIVOM Trial. Ann Surg 247:207–213
Andersson Y, de Boniface J, Jonsson PE, Ingvar C, Liljegren G, Bergkvist L et al, 2012, Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer. Br J Surg 99:226–231
Hunt KK, Ballman KV, McCall LM, Boughey JC, Mittendorf EA, Cox CE et al, 2012, Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial. Ann Surg 256:428–436
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP et al, 2010, Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically nodenegative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11:927– 933
Cserni G, Burzykowski T, Vinh-Hung V, Kocsis L, Boross G, Sinko M et al, 2004, Axillary sentinel node and tumour-related factors associated with non-sentinel node involvement in breast cancer. Jpn J Clin Oncol 34:519–524
Viale G, Maiorano E, Pruneri G, Mastropasqua MG, Valentini S, Galimberti V et al, 2005, Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy. Ann Surg 241:319–325
Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM et al, 2010, Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 252:426–432
Sola M, Alberro JA, Fraile M, Santesteban P, Ramos M, Fabregas R et al, 2013, Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastasis: final results from the multicenter clinical trial AATRM 048/13/2000. Ann Surg Oncol 20:120–127
Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P et al, 2013, Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases, IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 14:297–305
Park J, Fey JV, Naik AM, Borgen PI, Van Zee KJ, Cody HS 3rd, 2007, A declining rate of completion axillary dissection in sentinel lymph node-positive breast cancer patients is associated with the use of a multivariate nomogram. Ann Surg 245:462–468
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Wasif N, Maggard MA, Ko CY, Giuliano AE, 2010, Underuse of axillary dissection for the management of sentinel node micrometastases in breast cancer. Arch Surg 145: 161–166
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Grabau D, Dihge L, FernoM, Ingvar C, Ryden L, 2013, Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade’s experience from a single institution. EJSO 39:601–607
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Cserni G, 2002, Complete step sectioning of axillary sentinel lymph nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 55:926–931
Cserni G, Bezsenyi I, Marko L, 2013, Patients′ choice on axillary lymph node dissection following sentinel lymph node micrometastasis–first report on prospective use of a nomogram in very low risk patients. Pathol Oncol Res 19:211–216
Cserni G, Gregori D, Merletti F, Sapino A, Mano MP, Ponti A et al, 2004)Meta-analysis of non-sentinel nodemetastases associated with micrometastatic sentinel nodes in breast cancer. Br J Surg 91:1245– 1252
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Cserni G, Bianchi S, Vezzosi V, van Diest P, van Deurzen C, Sejben I et al, 2008, Variations in sentinel node isolated tumour cells / micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions. Eur J Cancer 44: 2185–2191
Meretoja TJ, Vironen JH, Heikkila PS, Leidenius MH, 2010, Outcome of selected breast cancer patients with micrometastasis or isolated tumor cells in sentinel node biopsy and no completion axillary lymph node dissection. J Surg Oncol 102: 215–219
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 861
EP 866
DI 10.1007/s12253-015-9899-6
PG 6
ER
PT J
AU Zhong, Dt
Wu, Rp
Wang, Xl
Huang, XB
Lin, Mx
Lan, Yq
Chen, Q
AF Zhong, Dong-ta
Wu, Ri-ping
Wang, Xin-li
Huang, Xiao-Bing
Lin, Meng-xin
Lan, Yan-qin
Chen, Qiang
TI Combination Chemotherapy with S-1 and Oxaliplatin (SOX) as First-Line Treatment in Elderly Patients with Advanced Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Advanced gastric cancer; S-1; Oxaliplatin; Elderly; Combination chemotherapy
ID Advanced gastric cancer; S-1; Oxaliplatin; Elderly; Combination chemotherapy
AB This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40–60 mg depending on patient’s body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m2 oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3–63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8–87.8 %). The median follow-up period was 23 months (range, 5–42 months). The median time to progression was 6.9 months (95 %CI, 5.5–8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4– 14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7–66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and welltolerated regimen for elderly patients with advanced gastric cancer.
C1 [Zhong, Dong-ta] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Wu, Ri-ping] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Wang, Xin-li] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Huang, Xiao-Bing] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Lin, Meng-xin] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Lan, Yan-qin] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
[Chen, Qiang] Fujian Medical University Union Hospital, Department of Medical Oncology, No. 29 Xinquan Road, 350001 Fuzhou, Fujian, China.
RP Chen, Q (reprint author), Fujian Medical University Union Hospital, Department of Medical Oncology, 350001 Fuzhou, China.
EM cqiang8@189.cn
CR Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ, 2009, Cancer statistics, 2009. CA Cancer J Clin 59:225–249
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Kato T, Shimamoto Y, Uchida J, Ohshimo H, Abe M, Shirasaka T, Fukushima M, 2001, Possible regulation of 5-fluorouracil-induced neuro- and oral toxicities by two biochemical modulators consisting of S-1, a new oral formulation of 5-fluorouracil. Anticancer Res 21: 1705–1712
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Hirata K, Horikoshi N, Tominaga K, Sohma K, Yamaguchi K, Okazaki M, Furuhata T, Sasaki K, Nakano Y, Ishizuka H, Yamada Y, Uno S, Taguchi T, Yamamitsu S, Shirasaka T, 2006, Pharmacokinetics of S-1. Gan To Kagaku Ryoho 33: 27–35
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M, 2008, S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer, SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 867
EP 873
DI 10.1007/s12253-015-9903-1
PG 7
ER
PT J
AU Quan, L
Qiu, T
Liang, J
Li, M
Zhang, Y
Tao, K
AF Quan, Liangliang
Qiu, Tao
Liang, Jiulong
Li, Miao
Zhang, Yu
Tao, Kai
TI Identification of Target Genes Regulated by KSHV miRNAs in KSHV-Infected Lymphoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kaposi’s sarcoma-associated herpesvirus; Gene; microRNAs; Functional annotation
ID Kaposi’s sarcoma-associated herpesvirus; Gene; microRNAs; Functional annotation
AB This study aimed to identify target genes regulated by KSHV miRNAs in KSHV-infected lymphoma cells. Original Ago HITS-CLIP data of BC-3 and BCBL-1 cell lines were downloaded from SRA database in NCBI, including mRNA and miRNA samples. The raw mRNA reads were mapped into human reference genome hg19 via TopHat for read alignment. PCR duplicates were removed via the SAM tool and the peaks of reads were analyzed via Cufflinks. For miRNA data, the raw data were mapped to the mature miRNA sequences based on miRBase via Bowtie. Peak intersection was computed by using intersectBed in BEDtools. Then, the mature miRNA seeds were identified and then were aligned with 3’ UTR merged peaks. The regulationships of miRNAs and their corresponding genes were analyzed based on the signal of RNA-induced silencing complex. Totally, 7 KSHV-related genes regulated by KSHV miRNAs were identified, including IPO5, EDA, NT5C3, WSB1, KCNS1, PRAM1 and MTRNR2L6. Among them, EDA, MTRNR2L6 and IPO5 were regulated by multiple KSHV miRNAs, such as kshv-miR-K12-1-5p, kshv-miR-K12-4-3p and kshv-miR-K12-3-5p, respectively. Furthermore, expression of kshv-miR-K12-1-5p and kshv-miR-K12-3-5p in BCBL-1 cell line were lower than that in BC-3 cell line, conversely, expression of kshv-miR-K12-4-3p in BCBL-1 cell line were higher than that in BC-3 cell line. In conclusion, potential target genes regulated by KSHV miRNAs in KSHV-infected lymphoma cells might play key roles in the nosogenesis of this disease. These findings might provide the basis for deep understanding of KSHV-infected tumors and further molecular experiments.
C1 [Quan, Liangliang] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
[Qiu, Tao] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
[Liang, Jiulong] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
[Li, Miao] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
[Zhang, Yu] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
[Tao, Kai] General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, No. 83 Wenhua Road, Shenhe District, 110016 Shenyang, Liaoning Province, China.
RP Tao, K (reprint author), General Hospital of Shenyang Military Area Command, Department of Plastic Surgery, 110016 Shenyang, China.
EM kaitaodr@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 875
EP 880
DI 10.1007/s12253-015-9902-2
PG 6
ER
PT J
AU Emami, N
Saadat, I
Omidvari, Sh
AF Emami, Naghmeh
Saadat, Iraj
Omidvari, Shahpour
TI Susceptibility to Colorectal Cancer and Two Genetic Polymorphisms of XRCC4
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Polymorphisms; XRCC4
ID Colorectal cancer; Polymorphisms; XRCC4
AB The X-ray complementing group 4 (XRCC4, OMIM: 194363) plays a key role in non-homologous endjoining DNA repair pathway in mammalian cells. This pathway is believed to help maintain genomic stability. In the present study, it is hypothesized that genetic polymorphisms in the NHEJ repair XRCC4 gene may be associated with an increased risk in developing colorectal cancer (CRC). We genotyped two polymorphisms of XRCC4, G-1394T (rs6869366) and intron 3 insertion/deletion (I/D; rs28360071) in 200 colorectal cancer patients as well as 256 healthy individuals, and evaluated their association with CRC. We found that in G-1394T polymorphism, neither the TG nor the GG genotypes (versus the TT genotype) were associated with the risk of developing CRC. The results of our study indicate that in comparison with the II genotype, ID and DD genotypes had no significant association with the risk of developing CRC. Subjects with TT genotype and positive family history in colorectal cancer were found to be at a much lower risk of developing CRC in comparison with the reference group (OR=0.31, 95%CI: 0.11–0.85, P=0.023). It should be noted that participants having at least one G allele (TG+GG genotypes) were at a significantly higher risk to develop the disease compared with the reference group (OR=9.10, 95%CI: 2.00–41.3, P=0.004). In relation to I/D polymorphism, among participants, those with positive family history, either with ID (OR=4.78, 95%CI: 2.26–10.0, P<0.001) or DD genotypes (OR=5.73, 95%CI: 1.99–16.4, P=0.001) had a significantly association with the disease. Among participants with a positive family history in CRC, the haplotype GD dramatically increased the risk of developing CRC (OR=10.2, 95%CI: 2.28–46, P=0.002). The results of this study indicate that G-1394T and I/D polymorphisms of XRCC4 among individuals with positive family history for colorectal cancer substantially increase the risk factor for developing colorectal cancers.
C1 [Emami, Naghmeh] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
[Saadat, Iraj] Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
[Omidvari, Shahpour] Shiraz University of Medical Sciences, Department of ChemotherapyShiraz, Iran.
RP Saadat, I (reprint author), Shiraz University, College of Sciences, Department of Biology, 71454 Shiraz, Iran.
EM isaadat@shirazu.ac.ir
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Chang CH, Chiu CF, Wang HC, Wu HC, Tsai RY, Tsai CW, Wang RF, Wang CH, Tsou YA, Bau DT, 2009, Significant association of ERCC6 single nucleotide polymorphisms with bladder cancer susceptibility in Taiwan. Anticancer Res 29: 5121–5124
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 881
EP 885
DI 10.1007/s12253-015-9905-z
PG 5
ER
PT J
AU Eduardo, GDPM
Campaner, BA
Silva, ALGM
AF Eduardo, Gamba De Paula Mariana
Campaner, Bittencourt Adriana
Silva, Antonieta Longo Galvao Maria
TI Apoptosis Phenomena in Squamous Cell Carcinomas and Adenocarcinomas of the Uterine Cervix
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Uterine cervix; Squamous cell carcinoma; Adenocarcinoma; Bcl-2 protein
ID Apoptosis; Uterine cervix; Squamous cell carcinoma; Adenocarcinoma; Bcl-2 protein
AB To investigate the relationship between apoptosis and histologic types in invasive squamous cell carcinoma and adenocarcinoma of the uterine cervix. The present study involved the assessment of surgical specimens from 74 women with cervical carcinomas FIGO stage IB1 (54 squamous cell carcinomas and 20 adenocarcinomas). The study samples were obtained from selected paraffin blocks containing specimens from patients submitted to surgical procedures. The respective medical charts of patients were reviewed and epidemiologic, clinical and disease-related data were collected. Cervical specimens were assessed by the immunohistochemistry technique using the Bcl-2 protein as a marker. The reactions were considered positive when the cells became stained in brown color. Bcl-2 positive cells were counted in 10 fields under a high magnification (400x) using light microscopy, in the slides area containing squamous carcinoma and adenocarcinoma of the cervix. The total cell count was expressed as the number of positive Bcl-2 cells per mm2. No significant difference in the number of cells marked by the Bcl-2 protein was found for the variables age, tumor diameter, angiolymphatic invasion or number of lymph nodes affected. Comparison of the number of cells marked by the Bcl-2 protein in the two histological groups revealed a statistically significant difference, with squamous tumors presenting a greater number of marked cells. Squamous cervical tumors present a greater number of positive Bcl-2 cells per mm2, suggesting that that the rate of cell death in squamous cell carcinomas of the cervix is lower than in adenocarcinomas.
C1 [Eduardo, Gamba De Paula Mariana] Santa Casa de Sao Paulo, School of Medicine, Department of Obstetrics and Gynecology, R. Cesario Mota Jr, 112 - Vila Buarque, 01221-020 Sao Paulo, SP, Brazil.
[Campaner, Bittencourt Adriana] Santa Casa de Sao Paulo, School of Medicine, Department of Obstetrics and Gynecology, R. Cesario Mota Jr, 112 - Vila Buarque, 01221-020 Sao Paulo, SP, Brazil.
[Silva, Antonieta Longo Galvao Maria] Santa Casa de Sao Paulo, School of Medicine, Department of Pathology, Rua Cesario Mota Jr 112 - Vila Buarque, 01221-020 Sao Paulo, SP, Brazil.
RP Campaner, BA (reprint author), Santa Casa de Sao Paulo, School of Medicine, Department of Obstetrics and Gynecology, 01221-020 Sao Paulo, Brazil.
EM abcampaner@terra.com.br
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 887
EP 892
DI 10.1007/s12253-015-9906-y
PG 6
ER
PT J
AU Alshenawy, AH
AF Alshenawy, AlSaeid Hanan
TI Immunohistochemical Panel for Differentiating Renal Cell Carcinoma with Clear and Papillary Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; CK7; Carbonic anhydrase IX; α-methylacyl-CoA-racemase; TFE-3
ID Renal cell carcinoma; CK7; Carbonic anhydrase IX; α-methylacyl-CoA-racemase; TFE-3
AB Renal cell carcinoma (RCC) in which clear cells with papillary architecture are present is a difficult diagnostic challenge. The most common type, clear cell RCC, only rarely has papillary architecture. The second most common one, papillary RCC, only rarely contains clear cells. However, two recently described less-common types, clear cell papillary and Xp11 translocation RCC characteristically feature both papillary architecture and cells with clear cytoplasm. Accurate diagnosis has both prognostic and therapeutic implications. This study aims to highlight the helpful cytomorphologic and immunohistochemical features of each of these entities to enable reproducible classification. Sixty RCC cases with clear cells and papillary architecture were selected and classified according to The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia and graded according to The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma then stained for CK7, carbonic anhydrase IX (CA IX), α- methylacyl-CoA-racemase (AMACR) and TFE-3. The characteristic immunoprofile of Clear RCC is CK7-, AMACR-, CA IX+ and TFE3-, papillary RCC is CK7+, AMACR+, CAIX- and TFE3-, while for clear cell papillary RCC it is CK7+, AMACR-, CAIX+ and TFE3- and lastly Xp11translocation RCC is CK7-, AMACR+, CAIX- and TFE3+. Immunohistochemical staining for CA IX, CK7, AMACR and TFE3 comprises a concise panel for distinguishing RCC with papillary and clear pattern.
C1 [Alshenawy, AlSaeid Hanan] Tanta University, Faculty of Medicine, Department of Pathology, 25 Hamdy Gado streetTanta, Egypt.
RP Alshenawy, AH (reprint author), Tanta University, Faculty of Medicine, Department of Pathology, Tanta, Egypt.
EM hanan_alshenawy@yahoo.com
CR Deng F, Melamed J, 2012, Histologic variants of renal cell carcinoma: does tumor type influence outcome? Urol Clin N Am 39:119–132
Zhanyong B, Priti L, Song L et al, 2013, Role of carbonic anhydrase IX, α-methylacyl coenzyme a racemase, cytokeratin 7, and galectin-3 in the evaluation of renal neoplasms: a tissue microarray immunohistochemical study. Ann Diagn Pathol 17:58–62
Sean R, John N, Liang C et al, 2013, Clear cell papillary renal cell carcinoma: differential diagnosis and extended immunohistochemical profile. Mod Pathol 26:697–708
Hillary R, Guido M, Pedram A, 2012, Renal cell carcinoma with clear cell and papillary features. Arch Pathol Lab Med 136:391–399 5 . Wal t e r B, Hartmann A, Hofstadter F et al, 2012, Immunohistochemical marker panel differentiates between the three most common subtypes of renal cell carcinoma independent from histomorphologic criteria. Virchows Arch 460:343–352 6. Borislav A, Cinthia B, 2014, Clear cell papillary renal cell carcinoma: incidence, morphological features, immunohistochemical profile, and biologic behavior: a single institution study. Pathol Res Pract 210:234–241 7. Rajen G, Elizabeth G, Ximing J et al, 2013, Differential diagnosis of renal tumors with clear cytoplasm: clinical relevance of renal tumor subclassification in the era of targeted therapies and personalized medicine. Arch Pathol Lab Med 137:467–480 8. Park J, Lee C, Suh J et al, 2012, Clear cell papillary renal cell carcinoma: a report of 15 cases including three cases of concurrent othertype renal cell carcinomas. Korean J Pathol 46:541–547 9. Saba K, Ozden T, Sumer B et al, 2008, Diagnostic utility of cytokeratins 7, 10 and 20 in renal cell carcinoma and oncocytoma. Turk J Pathol 24:140–146 10. Michelle P, Amy Z, Zhanyong B, 2013, Useful immunohistochemical panel for differentiating clear cell papillary renal cell carcinoma from its mimics. Ann Diagn Pathol 17:437–440 11. Elizabeth M, Musie G, Robert N et al, 2010, Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade. Am J Clin Pathol 134:873–879 12. John RS, Brett D, John NE et al, 2013, The International Society of Urological Pathology, ISUP, Vancouver classification of renal neoplasia. Am J Surg Pathol 37:1209–1220 13. Brett D, John CC, Guido M et al, 2013, The International Society of Urological Pathology, ISUP, grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 37(10):1490– 1504 14. Edge S, Byrd D, Compton C et al, eds,, 2010, AJCC cancer staging manual, 7th edn. Springer, New York, pp 479–489 15. Stephen M, Yonghong X, Yupu L et al, 2011, Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins. Mod Pathol 24:1207–1220 16. Brannon A, Haake S, Hacker K et al, 2012, Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology. Eur Urol 61:258– 268 17. Aydin H, Chen L, Cheng L et al, 2010, Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of the kidney. Am J Surg Pathol 34:608–1621 18. Duan L, Youseff R, Margulis Vet al, 2011, Clear cell papillary renal cell carcinoma: clinicopathologic, immunohistochemical, andmolecular analysis. Mod Pathol 24:189–193 19. Brunelli M, Menestrina F, Segala D et al, 2009, Renal cell carcinoma with prominent leiomyomatous proliferation appears not to be a variant of clear cell renal cell carcinoma. Mod Pathol 22:160– 165 20. Shen S, Truong L, Scarpelli M et al, 2012, Role of immunohistochemistry in diagnosing renal neoplasms: when is it really useful? Arch Pathol Lab Med 136:410–417 21. Al-Ahmadie H, Alden D et al, 2011, Role of immunohistochemistry in the evaluation of needle core biopsies in adult renal cortical tumors: an ex vivo study. Am J Surg Pathol 36:949–961 22. Tickoo S, Reuter V, 2011, Differential diagnosis of renal tumors with papillary architecture. Adv Anat Pathol 18:120–131
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 893
EP 899
DI 10.1007/s12253-015-9898-7
PG 7
ER
PT J
AU Al-Bahrani, R
Nagamori, S
Leng, R
Petryk, A
Sergi, C
AF Al-Bahrani, Redha
Nagamori, Seishi
Leng, Roger
Petryk, Anna
Sergi, Consolato
TI Differential Expression of Sonic Hedgehog Protein in Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Cholangiocarcinoma; Sonic hedgehog; Bone morphogenetic protein 4; Immunohistochemistry
ID Hepatocellular carcinoma; Cholangiocarcinoma; Sonic hedgehog; Bone morphogenetic protein 4; Immunohistochemistry
AB Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) are the two most common primary liver malignancies in adult patients. The molecular mechanisms underlying the pathogenesis of HCC and CCA are still poorly understood. Sonic hedgehog (SHH) signaling plays an essential role during mammalian development, i.e., promoting organ growth, tissue differentiation, and cell polarity. The upregulation of SHH has been observed during carcinogenesis, including colorectal carcinoma. Our aimwas to investigate the expression pattern of SHH in HCC and CCA.We investigated 40 malignant tumors of the liver, including 21 HCC and 19 of intrahepatic CCA cases by immunohistochemistry (IHC) using a polyclonal antibody against SHH and Avidin-Biotin Complex method. We also investigated the co-localization of SHH and Bone morphogenetic protein 4 (BMP4) in CCA using indirect double IHC. Moreover, we examined whether SHH is expressed in two HCC cell lines HepG2 and HuH-7 and three CCA cell lines OZ, HuCCT1 and HuH28.We found that SHH was expressed in 15 out of 21 cases (71.4 %) of HCC and 100 % of CCA cases by immunohistochemistry. SHH expression showed a positive trend in liver tumors (HCC, CCA) with high grade (G2-G3). SHH localized to the epithelial cells, while BMP4 was expressed in the stromal cells in CCA by double IHC. However, both HCC and CCA cell lines showed SHH expression by Western blot analysis. In conclusion, SHH seems to be an interesting marker of dedifferentiation in liver tumors and the simultaneous epithelial-mesenchymal expression may be an intriguing prompt to investigate cross-talks between SHH and BMP4.
C1 [Al-Bahrani, Redha] University of Alberta, Department of Laboratory Medicine and Pathology, 8440-112 Street, T6G 2B7 Edmonton, AB, Canada.
[Nagamori, Seishi] National Institute of Infectious Diseases, Department of Virology IITokyo, Japan.
[Leng, Roger] University of Alberta, Department of Laboratory Medicine and Pathology, 8440-112 Street, T6G 2B7 Edmonton, AB, Canada.
[Petryk, Anna] University of Minnesota, Department of PediatricsMinneapolis, MN, USA.
[Sergi, Consolato] University of Alberta, Department of Laboratory Medicine and Pathology, 8440-112 Street, T6G 2B7 Edmonton, AB, Canada.
RP Sergi, C (reprint author), University of Alberta, Department of Laboratory Medicine and Pathology, T6G 2B7 Edmonton, Canada.
EM sergi@ualberta.ca
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 901
EP 908
DI 10.1007/s12253-015-9918-7
PG 8
ER
PT J
AU Ramya, NL
Pulicherla, KK
AF Ramya, N L
Pulicherla, Kanth Krishna
TI Studies on Deimmunization of Antileukaemic L-Asparaginase to have Reduced Clinical Immunogenicity- An in silico Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE L- Asparaginase; Hypersensitive reactions; Neutralizing antibodies; Anaphylactic shock; Pectobacterium carotovorum; Immunogenicity; Acute lymphoblastic leukaemia
ID L- Asparaginase; Hypersensitive reactions; Neutralizing antibodies; Anaphylactic shock; Pectobacterium carotovorum; Immunogenicity; Acute lymphoblastic leukaemia
AB Protein therapeutics, particularly of heterologous origin are shown to elicit immunogenic responses which result in adverse allergic reactions in spite of their promising clinical benefit. L-Asparaginase is one such well known chemotherapeutic agent that has enhanced the survival rates to 90%in the treatment of acute lymphoblastic leukaemia for past 30 years. But the use of this enzyme is accompanied by hypersensitive reactions ranging from allergy to anaphylactic shock which have a drastic influence in treatment outcomes. Numerous attempts have been made to minimize the problems of immunogenicity, which remained as a major bottleneck in the treatment protocols. Conjugating the enzyme L- Asparaginase with PEG was successful as it has reduced the complications in therapy and frequency of injections (dosages), and thus became prominent in reducing the immunogenicity up to a certain extent. Keeping the bottlenecks in consideration during the development of therapeutics, the present study concentrates on engineering of protein as an alternative to the PEGylated enzyme, having reduced immunogenicity as an inbuilt character of protein by using in silico approaches. L-Asparaginase from Escherichia coli and Pectobacterium carotovorum were selected for the present study. The methodology consists of (i) locating the B and CD4+ T cell epitopes of enzyme by in silico tools (ii) generating point mutations of these epitopes to alter or reduce the immunogenicity of protein (iii) generating enzyme models by molecular modelling (iv) assessing the binding affinity of the substrate with L-Asparaginase variants by in silico docking methods using Autodock 4.2 and (v) validating the mutated model for stability by molecular dynamics simulation studies using Gromacs.
C1 [Ramya, N L] Acharya Nagarjuna University, Department of Biotechnology, Nagarjuna Nagar, 522510 Guntur, AP, India.
[Pulicherla, Kanth Krishna] VIT University, Center for Bioseparation Technology, 632014 Vellore, TN, India.
RP Pulicherla, KK (reprint author), VIT University, Center for Bioseparation Technology, 632014 Vellore, India.
EM kkpulicherla@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 909
EP 920
DI 10.1007/s12253-015-9912-0
PG 12
ER
PT J
AU Mostafavi-Pour, Z
Kianpour, S
Dehghani, M
Mokarram, P
Torabinejad, S
Monabati, A
AF Mostafavi-Pour, Zoherh
Kianpour, Sedigheh
Dehghani, Mehdi
Mokarram, Pooneh
Torabinejad, Simin
Monabati, Ahmad
TI Methylation of Integrin α4 and E-Cadherin Genes in Human Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Integrin α4; E-Cadherin; DU145; PC3; Prostate cancer; DNA methylation
ID Integrin α4; E-Cadherin; DU145; PC3; Prostate cancer; DNA methylation
AB Prostate cancer is the second most common malignancy in men worldwide. Abnormal epigenetic alterations such as DNA methylation and histone modification play an important role in tumor initiation, progression and regulation of cancer-related genes such as integrin α4 and E-cadherin. Expression of these genes was determined by semiquantitative reverse transcriptase-PCR in prostate cancer cell lines, DU145 and PC3, before and after treatment with 5-aza- 2-deoxycytidine and trichostatin A. Laser capture microdissection microscopy was used to obtain exclusively affected epithelial cells from prostate gland biopsies of 30 patients with prostate cancer and 40 with benign prostate hyperplasia. DNA bisulfite modifications followed by methylation-specific PCR were used to evaluate the promoter methylation status of Ecadherin and α4 integrin genes in extracted DNA from patients and aforementioned cell lines. The integrin α4 promoter in DU145 was fully methylated, whereas in PC3 cells, partial methylation was detected. E-cadherin was expressed in both cell lines; trichostatin A and 5-aza-2-deoxycytidine treatment had no effect on E-cadherin expression, however the combined treatment of both drugs or 5-aza-2-deoxycytidine alone increased integrin α4 expression. Integrin α4 and E-cadherin were hypermethylated in 66.6 % and 6.6 % of prostate cancer cases, respectively; no hypermethylation was observed in patients with benign prostate hyperplasia. These results together suggest that aberrant DNA methylation is one of the mechanisms involved in integrin α4 expression and may play an important role in human prostate carcinogenesis. In addition, the higher rate of integrin α4 gene methylation in prostate cancer patients elects it as a potential molecular tumor marker.
C1 [Mostafavi-Pour, Zoherh] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Kianpour, Sedigheh] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Dehghani, Mehdi] University of Texas Health Science Center, Department of Internal Medicine, Division of Oncology, 77030 Houston, TX, USA.
[Mokarram, Pooneh] Shiraz University of Medical Sciences, Department of BiochemistryShiraz, Iran.
[Torabinejad, Simin] Shiraz University of Medical Sciences, Shiraz Nephrourology Research CenterShiraz, Iran.
[Monabati, Ahmad] Medical School, Shiraz University of Medical Sciences, Department of PathologyShiraz, Iran.
RP Mostafavi-Pour, Z (reprint author), Shiraz University of Medical Sciences, Department of Biochemistry, Shiraz, Iran.
EM zmostafavipour88@yahoo.co.uk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 921
EP 927
DI 10.1007/s12253-015-9917-8
PG 7
ER
PT J
AU Alexandrakis, GM
Goulidaki, N
Pappa, AC
Boula, A
Psarakis, F
Neonakis, I
Tsirakis, G
AF Alexandrakis, G Michael
Goulidaki, Nektaria
Pappa, A Constantina
Boula, Anna
Psarakis, Fotios
Neonakis, Ioannis
Tsirakis, George
TI Interleukin-10 Induces Both Plasma Cell Proliferation and Angiogenesis in Multiple Myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiogenesis; Cytokines; Growth factors; Multiple myeloma
ID Angiogenesis; Cytokines; Growth factors; Multiple myeloma
AB In multiple myeloma the angiogenic process is enhanced by various mediators.Among them interleukin-10 (IL- 10), secreted mainly by myeloma-associated macrophages seems to participate in myeloma progression with variable manners. The aim of the study was to measure serum levels of IL-10 in various stages of MM patients and to correlate them with various angiogenic cytokines, such as vascular endothelial growth factor and angiopoietin-2 and with known proliferation parameters, such as serum levels of B-cell activating factor and bone marrow infiltration by myeloma plasma cells, in order to explore their clinical significance. We measured serum levels of the above parameters by ELISA in 54 newly diagnosed MM patients. All of them were higher in MM patients and were increasing in parallel with disease progression. Furthermore, IL-10 correlated positively with both angiogenic cytokines and proliferation markers. This correlation of IL-10 with both angiogenic cytokines and markers of disease activity implicates that they all have an important role in MM pathogenesis and progression.
C1 [Alexandrakis, G Michael] University Hospital of Heraklion, Hematology Department, Stavrakia, 71110 Heraklion, Crete, Greece.
[Goulidaki, Nektaria] University Hospital of Heraklion, Hematology DepartmentHeraklion, Greece.
[Pappa, A Constantina] University Hospital of Heraklion, Hematology DepartmentHeraklion, Greece.
[Boula, Anna] University Hospital of Heraklion, Hematology DepartmentHeraklion, Greece.
[Psarakis, Fotios] University Hospital of Heraklion, Hematology DepartmentHeraklion, Greece.
[Neonakis, Ioannis] University Hospital of Heraklion, Hematology DepartmentHeraklion, Greece.
[Tsirakis, George] University Hospital of Heraklion, Hematology Department, Stavrakia, 71110 Heraklion, Crete, Greece.
RP Tsirakis, G (reprint author), University Hospital of Heraklion, Hematology Department, 71110 Heraklion, Greece.
EM georgetsirakis@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 929
EP 934
DI 10.1007/s12253-015-9921-z
PG 6
ER
PT J
AU Michalska, MM
Samulak, D
Romanowicz, H
Smolarz, B
AF Michalska, M Magdalena
Samulak, Dariusz
Romanowicz, Hanna
Smolarz, Beata
TI Single Nucleotide Polymorphisms (SNPs) of RAD51-G172T and XRCC2-41657C/T Homologous Recombination Repair Genes and the Risk of Triple- Negative Breast Cancer in Polish Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RAD51; XRCC2; Triple negative breast cancer; Gene polymorphism
ID RAD51; XRCC2; Triple negative breast cancer; Gene polymorphism
AB Double strand DNA breaks are the most dangerous DNA damage which, if non-repaired or misrepaired, may result in genomic instability, cancer transformation or cell death. RAD51 and XRCC2 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of triple-negative breast cancer. The polymorphisms of the XRCC2 gene - 41657C/T (rs718282) and of the RAD51 gene, −172G/T (rs1801321), were investigated by PCR-RFLP in 70 patients with triple-negative breast cancer and 70 age- and sex matched non-cancer controls. The obtained results demonstrated a significant positive association between the RAD51 T/T genotype and TNBC, with an adjusted odds ratio (OR) of 4.94 (p=0.001). The homozygous T/T genotype was found in 60%of TNBC cases and in 14% of the used controls. Variant 172 Tallele of RAD51 increased cancer risk (OR=2.81 (1.72– 4.58), p<.0001). No significant associations were observed between -41657C/T genotype of XRCC2 and the incidence of TNBC. There were no significant differences between the distribution of XRCC2 -41657C/T genotypes in the subgroups assigned to histological grades. The obtained results indicate that the polymorphism of RAD51, but not of XRCC2 gene, may be positively associated with the incidence of triplenegative breast carcinoma in the population of Polish women.
C1 [Michalska, M Magdalena] Regional Hospital in Kalisz, Department of Obstetrics and GynaecologyKalisz, Poland.
[Samulak, Dariusz] Regional Hospital in Kalisz, Department of Obstetrics and GynaecologyKalisz, Poland.
[Romanowicz, Hanna] Regional Hospital in Glowno, High School of InformaticsGlowno, Poland.
[Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
RP Smolarz, B (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, 93-338 Lodz, Poland.
EM smolbea@wp.pl
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Romanowicz-Makowska H, Smolarz B, Gajecka M, Kiwerska K, Rydzanicz M, Kaczmarczyk D, Olszewski J, Szyfter K, Blasiak J, Morawiec-Sztandera A, 2012, Polymorphism of the DNA repair genes RAD51 and XRCC2 in smoking- and drinking-related laryngeal cancer in a Polish population. Arch Med Sci 8:1065–1075
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 935
EP 940
DI 10.1007/s12253-015-9922-y
PG 6
ER
PT J
AU Fang, WL
Huang, KH
Lan, YT
Chen, MH
Chao, Y
Lo, SSh
Wu, ChW
Shyr, YM
Li, FYA
AF Fang, Wen-Liang
Huang, Kuo-Hung
Lan, Yuan-Tzu
Chen, Ming-Huang
Chao, Yee
Lo, Su-Shun
Wu, Chew-Wun
Shyr, Yi-Ming
Li, Fen-Yau Anna
TI The Risk Factors of Lymph Node Metastasis in Early Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Early gastric cancer; Lymph node metastasis; Lymphatic invasion
ID Early gastric cancer; Lymph node metastasis; Lymphatic invasion
AB Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is an effective alternative treatment for early gastric cancer. However, a major concern is the likelihood of lymph node metastasis. From December 1987 to December 2006, 391 patients who underwent curative surgery for gastric cancer with mucosal (T1a, n=265) or submucosal (T1b, n=126) invasion and a retrieved lymph node number≧15 were enrolled. The frequency and risk factors of lymph node metastasis were analyzed. The frequency of lymph node metastasis was 4.9 % in T1a lesions and 21.4 % in T1b lesions. Although the depth of submucosal tumor invasion was<2 mm, there was a 28.6 % chance of lymph node metastasis. A T1b lesion, i.e., the width of the submucosal tumor invasion was<5 mm, resulted in fewer lymph node metastases than lesions>5 mm in width. Multivariate analysis demonstrated that Lauren’s diffuse type and lymphatic invasion were independent risk factors for lymph node metastasis in T1a lesions, while lymphatic invasion was the strongest risk factor for lymph node metastasis in T1b lesions. EMR/ESD is a good alternative for T1a intestinal type adenocarcinoma without lymphatic invasion. Surgical resection is necessary for patients with T1b gastric cancer with lymphatic invasion.
C1 [Fang, Wen-Liang] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Huang, Kuo-Hung] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Lan, Yuan-Tzu] Taipei Veterans General Hospital, Department of Surgery, Division of Colon & Rectal SurgeryTaipei, Taiwan, Republic of China.
[Chen, Ming-Huang] Taipei Veterans General Hospital, Department of Medicine, Division of Hematology and OncologyTaipei, Taiwan, Republic of China.
[Chao, Yee] Taipei Veterans General Hospital, Department of Medicine, Division of Hematology and OncologyTaipei, Taiwan, Republic of China.
[Lo, Su-Shun] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Wu, Chew-Wun] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Shyr, Yi-Ming] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Li, Fen-Yau Anna] Taipei Veterans General Hospital, Department of Pathology, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
RP Fang, WL (reprint author), Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, 11217 Taipei, Taiwan, Republic of China.
EM s821094@hotmail.com
CR Japanese Gastric Cancer Association, 2011, Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 14:101–112
Gotoda T, 2007, Endoscopic resection of early gastric cancer. Gastric Cancer 10:1–11
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Holscher AH, Drebber U, Monig SP et al, 2009, Early gastric cancer: lymph node metastasis starts with deep mucosal infiltration. Ann Surg 250:791–797
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Ye BD, Kim SG, Lee JY et al, 2008, Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer. J Gastroenterol Hepatol 23:46–50
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Kim H, Kim JH, Park JC et al, 2011, Lymphovascular invasion is an important predictor of lymph node metastasis in endoscopically resected early gastric cancers. Oncol Rep 25:1589–1595
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 941
EP 946
DI 10.1007/s12253-015-9920-0
PG 6
ER
PT J
AU Chen, H
Ye, Q
Lv, J
Ye, P
Sun, Y
Fan, Sh
Su, X
Gavine, P
Yin, X
AF Chen, Hao
Ye, Qingqing
Lv, Jing
Ye, Peng
Sun, Yun
Fan, Shuqiong
Su, Xinying
Gavine, Paul
Yin, Xiaolu
TI Evaluation of Trastuzumab Anti-Tumor Efficacy and its Correlation with HER-2 Status in Patient-Derived Gastric Adenocarcinoma Xenograft Models
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER2; Gastric carcinoma; Trastuzumab; Xenograft model antitumor assays; Fluorescence in situ hybridization; Immunohistochemistry
ID HER2; Gastric carcinoma; Trastuzumab; Xenograft model antitumor assays; Fluorescence in situ hybridization; Immunohistochemistry
AB The aimof the study was to investigate trastuzumab anti-tumor efficacy and its correlation with HER-2 status in primary xenograft models derived from Chinese patients with gastric adenocarcinoma. Patient-derived gastric adenocarcinoma xenograft (PDGAX) mouse models were firstly generated by implanting gastric adenocarcinoma tissues from patients into immune deficient mice. A high degree of histological and molecular similarity between the PDGAX mouse models and their corresponding patients’ gastric adenocarcinoma tissues was shown by pathological observation, HER-2 expression, HER-2 gene copy number, and mutation detection. Based on Hoffmann’s criteria in gastric cancer, three models (PDGAX001, PDGAX003 and PDGAX005) were defined as HER-2 positive with fluorescence in situ hybridization (FISH) amplification or immunohistochemistry (IHC) 2+/ 3+, while two models (PDGAX002, PDGAX004) were defined as HER-2 negative. Upon trastuzumab treatment, significant tumor regression (105 % TGI) was observed in model PDGAX005 (TP53 wt), while moderate sensitivity (26 % TGI) was observed in PDGAX003, and resistance was observed in PDGAX001, 002 and 004. A significant increase in HER-2 gene copy number was only observed in PDGAX005 (TP53 wt). Interestingly, trastuzumab showed no efficacy in PDGAX001 (HER2 IHC 3+ and FISH amplification, but with mutant TP53). Consistent with this finding, phosphor-HER2 modulation by trastuzumab was observed in model PDGAX005, but not in PDGAX001.
C1 [Chen, Hao] Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Department of General Surgery, No. 160 Pujian Road, 200127 Shanghai, China.
[Ye, Qingqing] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Lv, Jing] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Ye, Peng] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Sun, Yun] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Fan, Shuqiong] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Su, Xinying] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Gavine, Paul] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
[Yin, Xiaolu] AstraZeneca R&D, Asia & Emerging Market iMed, 199 Liangjing Road, 201203 Shanghai, China.
RP Yin, X (reprint author), AstraZeneca R&D, Asia & Emerging Market iMed, 201203 Shanghai, China.
EM lucy.yin@astrazeneca.com
CR Kaur A, Dasanu CA, 2011, Targeting the her2 pathway for the therapy of lower esophageal and gastric adenocarcinoma. Expert Opin Pharmacother 12:2493–2503
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Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, Ochiai A, 2006, Comparison of her2 gene amplification assessed by fluorescence in situ hybridization and her2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 15:65–71
Mackenzie M, Spithoff K, Jonker D, 2011, Systemic therapy for advanced gastric cancer: a clinical practice guideline. Curr Oncol 18:e202–209
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 947
EP 955
DI 10.1007/s12253-015-9909-8
PG 9
ER
PT J
AU Garay, T
Molnar, E
Juhasz,
Laszlo, V
Barbai, T
Dobos, J
Schelch, K
Pirker, Ch
Grusch, M
Berger, W
Timar, J
Hegedus, B
AF Garay, Tamas
Molnar, Eszter
Juhasz, Eva
Laszlo, Viktoria
Barbai, Tamas
Dobos, Judit
Schelch, Karin
Pirker, Christine
Grusch, Michael
Berger, Walter
Timar, Jozsef
Hegedus, Balazs
TI Sensitivity of Melanoma Cells to EGFR and FGFR Activation but Not Inhibition is Influenced by Oncogenic BRAF and NRAS Mutations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; BRAF; NRAS; Mutation; EGF; FGF2; EGFR inhibitor; FGFR inhibitor
ID Melanoma; BRAF; NRAS; Mutation; EGF; FGF2; EGFR inhibitor; FGFR inhibitor
AB BRAF and NRAS are the two most frequent oncogenic driver mutations in melanoma and are pivotal components of both the EGF and FGF signaling network. Accordingly, we investigated the effect of BRAF and NRAS oncogenic mutation on the response to the stimulation and inhibition of epidermal and fibroblast growth factor receptors in melanoma cells. In the three BRAF mutant, two NRAS mutant and two double wild-type cell lines growth factor receptor expression had been verified by qRT-PCR. Cell proliferation and migration were determined by the analysis of 3- days-long time-lapse videomicroscopic recordings. Of note, a more profound response was found in motility as compared to proliferation and double wild-type cells displayed a higher sensitivity to EGF and FGF2 treatment when compared to mutant cells. Both baseline and induced activation of the growth factor signaling was assessed by immunoblot analysis of the phosphorylation of the downstream effectors Erk1/2. Low baseline and higher inducibility of the signaling pathway was characteristic in double wild-type cells. In contrast, oncogenic BRAF or NRAS mutation did not influence the response to EGF or FGF receptor inhibitors in vitro. Our findings demonstrate that the oncogenic mutations in melanoma have a profound impact on the motogenic effect of the activation of growth factor receptor signaling. Since emerging molecularly targeted therapies aim at the growth factor receptor signaling, the appropriate mutational analysis of individual melanoma cases is essential in both preclinical studies and in the clinical trials and practice.
C1 [Garay, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Molnar, Eszter] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Juhasz, Eva] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Laszlo, Viktoria] Medical University of Vienna, Department of Thoracic Surgery, Spitalgasse 23, A-1090 Vienna, Austria.
[Barbai, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Dobos, Judit] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Schelch, Karin] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal Pathology, Borschkegasse 8a, A-1090 Vienna, Austria.
[Pirker, Christine] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal Pathology, Borschkegasse 8a, A-1090 Vienna, Austria.
[Grusch, Michael] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal Pathology, Borschkegasse 8a, A-1090 Vienna, Austria.
[Berger, Walter] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal Pathology, Borschkegasse 8a, A-1090 Vienna, Austria.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Hegedus, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Hegedus, B (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
CR Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM(2006, Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem 281(23): 15694–15700., DOI 10.1074/jbc.M601252200
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 957
EP 968
DI 10.1007/s12253-015-9916-9
PG 12
ER
PT J
AU Tsvetkova, A
Todorova, A
Todorov, T
Georgiev, G
Drandarska, I
Mitev, V
AF Tsvetkova, Anita
Todorova, Albena
Todorov, Tihomir
Georgiev, Georgi
Drandarska, Ivanka
Mitev, Vanyo
TI Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian Probands
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CRPC; Molecular subtyping; Prostate cancer; PCA3; TMPRSS2:ERG gene fusions; Prognosis
ID CRPC; Molecular subtyping; Prostate cancer; PCA3; TMPRSS2:ERG gene fusions; Prognosis
AB To correlate the molecular data to the clinicopathological parameters in Bulgarian prostate cancer patients. PCA3 overexpression, TMPRSS2-ERG gene fusion, GSTP1 promoter hypermethylation, somatic mutations in the AR gene and the IVS1-27G > A polymorphism in the KLF6 gene were studied. A total of 148 patients were analyzed: 16 aggressive PCa, 83 non-aggressive PCa, 25 BPH and 24 chronic inflammatory diseases. Real-time RT-PCR, DNA sequencing, and bisulfite conversion of DNA, were applied. All cases with aggressive PCa before treatment were tested positive for PCA3 overexpression, expression of a T2-ERG gene fusion product and GSTP1 promoter hypermethylation. No somatic mutations were detected in the AR gene and all patients showed normal KLF6-IVS1-27G > A genotype. The TMPRSS2-ERG positive status correlates with moderate to poorly differentiated prostate tumors and it is considered as unfavorable disease predictor. Positive GSTP1 promoter hypermethylation seems to be highly specific and the earliest epigenetic change in the prostate gland, which indicates the beginning of the pathological process. The appearance of positive molecular markers in blood was considered as a predictor of PCa dissemination. GSTP1 promoter hypermethylation was found as the earliest and a long-lasting epigenetic marker in blood samples of PCa patients, which makes it suitable as a marker for treatment follow-up. The molecular profile of prostate cancer needs to be strictly monitored during the course of disease treatment, which is of a great help in determining the patient’s individual therapy response.
C1 [Tsvetkova, Anita] Medical University - Sofia, Department of Medical Chemistry and BiochemistrySofia, Bulgaria.
[Todorova, Albena] Medical University - Sofia, Department of Medical Chemistry and BiochemistrySofia, Bulgaria.
[Todorov, Tihomir] Genetic Medico-Diagnostic LaboratorySofia, Bulgaria.
[Georgiev, Georgi] Military Medical Academy, Department of UrologySofia, Bulgaria.
[Drandarska, Ivanka] Military Medical Academy, Department of PathologySofia, Bulgaria.
[Mitev, Vanyo] Medical University - Sofia, Department of Medical Chemistry and BiochemistrySofia, Bulgaria.
RP Tsvetkova, A (reprint author), Medical University - Sofia, Department of Medical Chemistry and Biochemistry, Sofia, Bulgaria.
EM annita_25@abv.bg
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PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 969
EP 976
DI 10.1007/s12253-015-9915-x
PG 8
ER
PT J
AU Rusz, O
Voros, A
Varga, Z
Kelemen, Gy
Uhercsak, G
Nikolenyi, A
Ormandi, K
Simonka, Zs
Kahan, Zs
AF Rusz, Orsolya
Voros, Andras
Varga, Zoltan
Kelemen, Gyongyi
Uhercsak, Gabriella
Nikolenyi, Aliz
Ormandi, Katalin
Simonka, Zsolt
Kahan, Zsuzsanna
TI One-Year Neoadjuvant Endocrine Therapy in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Hormone sensitivity; Letrozole; Tamoxifen; Neoadjuvant endocrine therapy; Predictive factors
ID Breast cancer; Hormone sensitivity; Letrozole; Tamoxifen; Neoadjuvant endocrine therapy; Predictive factors
AB The evaluation of the effects of 1-year endocrine therapy (NET) was aimed at. A retrospective analysis of 42 cases with 46 stage II–III invasive, hormone receptor-positive, HER2-negative breast cancers was performed. One-year NET was planned with letrozole (n=33, postmenopausal group), or with goserelin plus letrozole (n=7) or with goserelin plus tamoxifen (n=2) (premenopausal group). Surgery was performed in accordance with the initial stage and the response to therapy. With regard to the tumor remaining in the surgical specimen, risk groups were constructed: Group 1: stage 0, pathological complete regression (pCR); Group 2: stages IAIIA; Group 3: stages ≥IIB + cases with clinical progression. Due to local progression, NET was replaced by neoadjuvant chemotherapy in three patients (four tumors). In two postmenopausal patients, letrozole was replaced by tamoxifen because of the insufficient treatment effect. In 19/42 cases, breastconserving surgery was performed. Within Group 1, there was no cancer in four cases, while only DCIS remained in 2 (pCR: 13 %); Groups 2 and 3 comprised 25 and 15 cases, respectively. The likeliness of a good response (Groups 1 and 2 vs. Group 3) to NET was increased by 7 % for every 1 % increase of the expression of ER (OR=1.070; 95 % CI: 1.007–1.138, p=0.029). Progression-free survival differed according to treatment response (p=0.001). The post-therapy Ki67 value of ≤15 % had only a marginal effect on survival. No other associations were detected between the tumor characteristics and the therapeutic response or survival. Longduration NET is effective and safe in cases of hormonesensitive breast cancer.
C1 [Rusz, Orsolya] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Voros, Andras] University of Szeged, Department of PathologySzeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Kelemen, Gyongyi] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Uhercsak, Gabriella] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Nikolenyi, Aliz] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Ormandi, Katalin] University of Szeged, Department of RadiologySzeged, Hungary.
[Simonka, Zsolt] University of Szeged, Department of SurgerySzeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM kahan.zsuzsanna@med.u-szeged.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 977
EP 984
DI 10.1007/s12253-015-9911-1
PG 8
ER
PT J
AU Kravchick, S
Lobik, L
Cytron, Sh
Kravchenko, Y
Dor, BD
Peled, R
AF Kravchick, Sergey
Lobik, Leonid
Cytron, Shmuel
Kravchenko, Yakov
Dor, Ben David
Peled, Ronit
TI Patients with Persistently Elevated PSA and Negative Results of TRUS-Biopsy: Does 6-Month Treatment with Dutasteride can Indicate Candidates for Re-Biopsy. What is the Best of Saturation Schemes: Transrectal or Transperineal Approach?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Biopsy; Elevated PSA; Dutasteride
ID Prostate cancer; Biopsy; Elevated PSA; Dutasteride
AB To identify patients who actually need a re - biopsy, based on alterations in PSA readings after 6-month treatment with Dutasteride. We also sought to bring out the most beneficial re-biopsy scheme. We have reviewed the records of patients with persistently elevated PSA and at least one set of TRUS biopsies. Patients who were treated with alpha - blockers/Dutasteride combination were considered as the study group, while patients in control received alphablockers alone. Patients in both groups underwent re-biopsy 6 months later. The two protocols of re-biopsies were used at that time: 20-24 cores saturation transrectal (ST)) and ≥40 cores saturation transperineal template-guided (STT) biopsies. One hundred thirty-three patients were included in this study. In 86.7 % of the patients in the study group mean PSA decreased from 7.4±2.69 to 4.037±1.53 (p-0.001). The overall cancer detection rate was 29 % (n-39: 19 v/s 20, control and study groups, respectively). In the study group PSA decreased to 26.73±11.26 % in patients with cancer, compared with 40.54±13.3 % in patients without. It must be emphasized that STT-biopsies detected significantly more cancers (38.46 v/s 20.59 %, p- 0.005). Mean cores number got to 21±2.45 and 45±5.65 in ST and STT biopsies, respectively. Six-month treatment with Dutasteride decreases PSA readings in 86.7 % of the patients. A PSA decline of less than 40% (cutoff) should be considered as an indicator for re-biopsy. Transperineal template-guided biopsies had a higher cancer detection rate.
C1 [Kravchick, Sergey] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Lobik, Leonid] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Cytron, Shmuel] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Kravchenko, Yakov] Barzialy Medical Center, Pathology DepartmentAshkelon, Israel.
[Dor, Ben David] Barzialy Medical Center, Pathology DepartmentAshkelon, Israel.
[Peled, Ronit] Ben Gurion University, Epidemiology and StatisticsBeer-Sheva, Israel.
RP Kravchick, S (reprint author), Barzialy Medical Center, Urology Department, Ashkelon, Israel.
EM kravchick.sergey@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 985
EP 989
DI 10.1007/s12253-015-9910-2
PG 5
ER
PT J
AU Josa, V
Krzystanek, M
Vass, T
Lang, T
Juhasz, V
Szilagyi, K
Tihanyi, B
Harsanyi, L
Szallasi, Z
Salamon, F
Baranyai, Zs
AF Josa, Valeria
Krzystanek, Marcin
Vass, Tamas
Lang, Tamas
Juhasz, Viktoria
Szilagyi, Kamilla
Tihanyi, Balazs
Harsanyi, Laszlo
Szallasi, Zoltan
Salamon, Ferenc
Baranyai, Zsolt
TI Thrombocytosis of Liver Metastasis from Colorectal Cancer as Predictive Factor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thrombocytosis; Liver metastasis of colorectal cancer; Prognostic factor; Survival
ID Thrombocytosis; Liver metastasis of colorectal cancer; Prognostic factor; Survival
AB There is increasing evidence that thrombocytosis is associated with tumor invasion and metastasis formation. It was shown in several solid tumor types that thrombocytosis prognosticates cancer progression. The aim of this study was to evaluate preoperative thrombocytosis as a potential prognostic biomarker in isolated metastases, in patients with liver metastasis of colorectal cancer (mCRC). Clinicopathological data of 166 patients with mCRC who had surgical resection between 2001 and 2011 were collected retrospectively. All primary tumors have been already resected. The platelet count was evaluated based on the standard preoperative blood profile. The patients were followed-up on average for 28 months. Overall survival (OS) of patients with thrombocytosis was significantly worse both in univariate (HR=3.00, p=0.03) and in multivariate analysis (HR=4.68, p=0.056) when adjusted for gender, age, tumor size and surgical margin. Thrombocytosis was also a good prognosticator of diseasefree survival (DFS) with HR=2.7, p=0.018 and nearly significant in multivariate setting (HR=2.26, p=0.073). The platelet count is a valuable prognostic marker for the survival in patients with mCRC.
C1 [Josa, Valeria] Tumorgenetika Human Biospecimen Collection and Research, Kerekgyarto u. 36, 1147 Budapest, Hungary.
[Krzystanek, Marcin] Technical University of Denmark, Department of Systems Biology, Kemitorvet Building 208, 2800 Kgs. Lyngby, Denmark.
[Vass, Tamas] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1082 Budapest, Hungary.
[Lang, Tamas] Szent Istvan Hospital, Department of General Surgery, Nagyvarad ter 1, 1097 Budapest, Hungary.
[Juhasz, Viktoria] Bajcsy Hospital, Department of Surgery, Maglodi ut 89-91, 1106 Budapest, Hungary.
[Szilagyi, Kamilla] HDF Medical Centre, Department of Otorhinolaryngology and Head and Neck Surgery, Podmaniczky utca 109-111, 1062 Budapest, Hungary.
[Tihanyi, Balazs] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1082 Budapest, Hungary.
[Harsanyi, Laszlo] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1082 Budapest, Hungary.
[Szallasi, Zoltan] Technical University of Denmark, Department of Systems Biology, Kemitorvet Building 208, 2800 Kgs. Lyngby, Denmark.
[Salamon, Ferenc] Fovarosi Uzsoki utcai Korhaz, Pathologia, Uzsoki u. 29-41, 1145 Budapest, Hungary.
[Baranyai, Zsolt] Semmelweis University, 1st Department of Surgery, Ulloi ut 78, 1082 Budapest, Hungary.
RP Baranyai, Zs (reprint author), Semmelweis University, 1st Department of Surgery, 1082 Budapest, Hungary.
EM barazso@gmail.com
CR Kanavos P, Schurer W, 2010, The dynamics of colorectal cancer management in 17 countries. Eur J Health Econ 10(Suppl 1):S115– S129
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 991
EP 997
DI 10.1007/s12253-015-9925-8
PG 7
ER
PT J
AU Wieczorek, A
Balwierz, W
AF Wieczorek, Aleksandra
Balwierz, Walentyna
TI The Role of Id2 Protein in Neuroblatoma in Children
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroblastoma; Id2 protein; Prognostic factor
ID Neuroblastoma; Id2 protein; Prognostic factor
AB Id (DNA binding and/or differentiation) proteins occur physiologically during ontogenesis and negatively regulate the activity of other helix-loop-helix (HLH) proteins. Id2 protein causes block of cells differentiation in the S phase of the cell cycle and regulates the activity of Rb protein. The role of Id2 protein in physiological cell cycle progression and in neuroblastoma (NBL) pathogenesis was proposed by Lasorella. The aim of the study was evaluation of Id2 expression and its prognostic significance in NBL cells coming from primary tumors and evaluation of its prognostic significance, and correlation of Id2 expression with known prognostic factors. Sixty patients with primary NBL treated from 1991 to 2005 were included in the analysis.We found 50 patients with high and 10 patients with low intensity of Id2 expression. The median percentage of NBL cells with Id2 expression was 88 %. We found no correlation between the number of NBL cells or the intensity of Id2 expression and OS and DFS. In patients with stage 4 NBL, almost all patients had high expression of Id2 and it was significantly more common than in other disease stages (p=0,03). We found no correlation between Id2 expression and other known prognostic factor in NBL patients. We assume that Id2 is not prognostic factor. However, due to its abundant expression in most of NBL cells and its role in cell cycle, it may be potential therapeutic target. Exact knowledge of expression time may be helpful in explaining mechanisms of oncogenesis.
C1 [Wieczorek, Aleksandra] Jagiellonian University Medical College, Polish-American Institute of Pediatrics, Department of Pediatric Oncology and HematologyKrakow, Poland.
[Balwierz, Walentyna] Jagiellonian University Medical College, Polish-American Institute of Pediatrics, Department of Pediatric Oncology and HematologyKrakow, Poland.
RP Wieczorek, A (reprint author), Jagiellonian University Medical College, Polish-American Institute of Pediatrics, Department of Pediatric Oncology and Hematology, Krakow, Poland.
EM a.wieczorek@uj.edu.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 999
EP 1004
DI 10.1007/s12253-015-9908-9
PG 6
ER
PT J
AU Micsik, T
Kiszler, G
Szabo, D
Krecsak, L
Hegedus, Cs
Krenacs, T
Molnar, B
AF Micsik, Tamas
Kiszler, Gabor
Szabo, Daniel
Krecsak, Laszlo
Hegedus, Csaba
Krenacs, Tibor
Molnar, Bela
TI Computer Aided Semi-Automated Evaluation of HER2 Immunodetection—A Robust Solution for Supporting the Accuracy of Anti HER2 Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Digital pathology; Validation; Image analysis; HER2; Immunohistochemistry
ID Breast cancer; Digital pathology; Validation; Image analysis; HER2; Immunohistochemistry
AB HER2-positive breast cancers usually benefit from anti-HER2 therapy, thus, HER2 evaluation became inevitable for patient selection. HER2-negative (IHC 0, 1+) and strong positive (IHC 3+) cases can easily be interpreted with immunohistochemistry, but equivocal (IHC 2+) cases require further analysis of HER2 gene amplification using in situ hybridization. Our study aimed to validate digital pathology and automated image analysis for unbiased evaluation of HER2 immunostains. We developed an image segmentation algorithm for analyzing HER2-immunostaining (4B5 clone) in tissue microarrays of breast cancers. Two pathologists assessed 309 microscopic regions of at least 100 tumor cells each— representing all HER2 positivity groups—according to international guidelines either semi-quantitatively or by using the MembraneQuant software. Scoring results were statistically correlated with each other and with FISH data, and almost perfect agreement was found (inter-method Cohen’s kappa=0.872, Spearman-rho=0.928). When clinical relevance (scoring disagreement that may define erroneous treatment selection) was examined high agreement was found (quadratic weighted kappa=0.967). Image analysis classified cases with excellent correlation with visual evaluation, therefore, MembraneQuant software proved to be a reliable tool for assessing HER2 immunoreactions and supporting better targeting anti-HER2 therapy. As digital analysis of immunomorphological markers allows permanent archiving, standardization and accurate reviewing of results, it supports quality assurance initiatives in diagnostic pathology—especially of equivocal cases which are hard to interpret.
C1 [Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi u. 26, 1085 Budapest, Hungary.
[Kiszler, Gabor] 3D HISTECH KftBudapest, Hungary.
[Szabo, Daniel] 3D HISTECH KftBudapest, Hungary.
[Krecsak, Laszlo] 3D HISTECH KftBudapest, Hungary.
[Hegedus, Csaba] 3D HISTECH KftBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi u. 26, 1085 Budapest, Hungary.
[Molnar, Bela] 3D HISTECH KftBudapest, Hungary.
RP Micsik, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM micsikt@gmail.com;micsikt@mail.korb1.sote.hu
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Choritz H, Busche G, Kreipe H, 2011, Quality assessment of HER2 testing by monitoring of positivity rates. Virchows Arch 459(3):283– 289., DOI 10.1007/s00428-011-1132-8
Dobson L, Conway C, Hanley A, Johnson A, Costello S, O’Grady A, Connolly Y, Magee H, O’Shea D, Jeffers M, Kay E, 2010, Image analysis as an adjunct to manual HER-2 immunohistochemical review: a diagnostic tool to standardize interpretation. Histopathology 57(1):27–38., DOI 10.1111/j.1365-2559.2010.03577.x
Gavrielides MA, Gallas BD, Lenz P, Badano A, Hewitt SM, 2011, Observer variability in the interpretation of HER2/neu immunohistochemical expressionwith unaided and computer-aided digitalmicroscopy. Arch Pathol Lab Med 135(2):233–242., DOI 10.1043/1543- 2165-135.2.233
Tuominen VJ, Tolonen TT, Isola J, 2012, ImmunoMembrane: a publicly available web application for digital image analysis of HER2 immunohistochemistry. Histopathology 60(5):758–767., DOI 10.1111/ j.1365-2559.2011.04142.x
Brey EM, Lalani Z, Johnston C, Wong M, McIntire LV, Duke PJ, Patrick CW Jr, 2003, Automated selection of DAB-labeled tissue for immunohistochemical quantification. J Histochem Cytochem 51(5): 575–584
Bloom K, Harrington D, 2004, Enhanced accuracy and reliability of HER-2/neu immunohistochemical scoring using digital microscopy. Am J Clin Pathol 121(5):620–630., DOI 10.1309/y73u-8x72-b68tmgh5
Lehr HA, Jacobs TW, Yaziji H, Schnitt SJ, Gown AM, 2001, Quantitative evaluation of HER-2/neu status in breast cancer by fluorescence in situ hybridization and by immunohistochemistry with image analysis. Am J Clin Pathol 115(6):814–822., DOI 10.1309/ aj84-50ak-1x1b-1q4c
Ciampa A, Xu B, Ayata G, Baiyee D, Wallace J, Wertheimer M, Edmiston K, Khan A, 2006, HER-2 status in breast cancer: correlation of gene amplification by FISH with immunohistochemistry expression using advanced cellular imaging system. Appl Immunohistochem Mol Morphol 14(2):132–137., DOI 10.1097/01. pai.0000150516.75567.13
Keller B, Chen W, Gavrielides MA, 2012, Quantitative assessment and classification of tissue-based biomarker expression with color content analysis. Arch Pathol Lab Med 136(5):539–550., DOI 10. 5858/arpa.2011-0195-OA
Krecsak L, Micsik T, Kiszler G, Krenacs T, Szabo D, Jonas V, Csaszar G, Czuni L, Gurzo P, Ficsor L, Molnar B, 2011, Technical note on the validation of a semi-automated image analysis software application for estrogen and progesterone receptor detection in breast cancer. Diagn Pathol 6:6., DOI 10.1186/1746-1596-6-6
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, BilousM, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, 2013, Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013., DOI 10.1200/jco.2013.50.9984
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Martin V, Camponovo A, Ghisletta M, Bongiovanni M, Mazzucchelli L, 2012, Internal Quality Assurance Program for ERBB2, HER2, testing improves the selection of breast cancer patients for treatment with Trastuzumab. Pathol Res Int 2012:261857., DOI 10.1155/2012/261857
Roche PC, Suman VJ, Jenkins RB, Davidson NE, Martino S, Kaufman PA, Addo FK, Murphy B, Ingle JN, Perez EA, 2002, Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst 94(11):855–857
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Andersson J, Linderholm B, Bergh J, Elmberger G, 2004, HER-2/ neu, c-erbB-2, evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol 12(1):14–20
Shin SJ, Hyjek E, Early E, Knowles DM, 2006, Intratumoral heterogeneity of her-2/neu in invasive mammary carcinomas using fluorescence in-situ hybridization and tissue microarray. Int J Surg Pathol 14(4):279–284., DOI 10.1177/1066896906293055
Joshi AS, Sharangpani GM, Porter K, Keyhani S, Morrison C, Basu AS, Gholap GA, Gholap AS, Barsky SH, 2007, Semi-automated imaging system to quantitate Her-2/neu membrane receptor immunoreactivity in human breast cancer. Cytometry A 71(5):273–285., DOI 10.1002/cyto.a.20374
Health CfDaR, 2007, 510(k, substantial equivalence determination decision summary for Aperio Technologies, Inc. ScanScope® XT System, IHC HER2/neu Image Analysis Application. Food and Drug Administration. http://www.accessdata.fda.gov/cdrh_docs/ reviews/K071128.pdf. Accessed 28 Mar 2013
Health CfDaR, 2004, 510(k, substantial equivalence determination decision summary for Applied Imaging Corporation, Applied Imaging Ariol™ with HER2 Application. Food and Drug Administration. http://www.accessdata.fda.gov/cdrh_docs/pdf3/ k032113.pdf. Accessed 28 Mar 2013
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Micsik TKG, Szabo D, Krecsak L, Krenacs T, Molnar B, 2013, Is HER2 amplification predictable by digital immunohistochemistry? Diagn Pathol 8(Suppl 1):S14
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1005
EP 1011
DI 10.1007/s12253-015-9927-6
PG 7
ER
PT J
AU Li, J
Hu, G
Kong, F
Wu, K
Song, K
He, J
Sun, W
AF Li, Jian
Hu, Guohuang
Kong, Fujiao
Wu, Kemin
Song, Kun
He, Jianfeng
Sun, Weijia
TI Elevated STMN1 Expression Correlates with Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic ductal adenocarcinoma (PDAC); STMN1; Prognosis
ID Pancreatic ductal adenocarcinoma (PDAC); STMN1; Prognosis
AB STMN1 is a cytosolic phosphoprotein that not only participates in cell division, but also plays an important role in other microtubule-dependent processes, such as cell motility. Furthermore, STMN1 acts as a "relay protein" in several intracellular signaling pathways that influence cell growth and differentiation. Thus, STMN1 is likely to support cellular processes essential for tumor progression: survival and migration. Indeed, elevated STMN1 expression has been reported in various types of human malignancies and is correlated with poor prognosis in these human malignancies. However, the clinical and prognostic significance of STMN1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, we assessed STMN1 in PDAC in this retrospective study.We first examined STMN1 expression in PDAC tissues from 27 cases and matched adjacent non-cancerous tissues by quantitative polymerase chain reaction (PCR) and western blot analyses. Next, immunohistochemistry was used to evaluate STMN1 expression in 87 archived paraffin-embedded PDAC specimens. STMN1 mRNA and protein expression levels were to a large extent up-regulated in PDAC tissue compared with their adjacent non-cancerous tissues. Moreover, STMN1 expression was closely correlated with histological differentiation, lymphatic metastasis, and TNM stage (P= 0.023, 0.047, and 0.014, respectively). In addition, PDAC patients with higher STMN1 expression died sooner than those with lower STMN1 expression (P<0.01). Multivariate analysis demonstrated that STMN1 expression was an independent prognostic factor for PDAC patients (P<0.01). Herein, we provide the first evidence that up-regulated STMN1 may contribute to tumor progression and poor prognosis in PDAC patients and may serve as a novel prognostic marker.
C1 [Li, Jian] Central South University, Xiangya Hospital, Department of PET centerChangsha, China.
[Hu, Guohuang] The fourth Hospital of Changsha, Department of General SurgeryChangsha, China.
[Kong, Fujiao] Central South University, Xiangya Hospital, Department of AnesthesiologyChangsha, China.
[Wu, Kemin] Central South University, Xiangya Hospital, Department of General SurgeryChangsha, China.
[Song, Kun] Central South University, Xiangya Hospital, Department of General SurgeryChangsha, China.
[He, Jianfeng] Central South University, Xiangya Hospital, Department of General SurgeryChangsha, China.
[Sun, Weijia] Central South University, Xiangya Hospital, Department of General SurgeryChangsha, China.
RP Sun, W (reprint author), Central South University, Xiangya Hospital, Department of General Surgery, Changsha, China.
EM sunweijia2013@126.com
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Kouzu Y, Uzawa K, Koike H, Saito K, Nakashima D, Higo M, Endo Y, Kasamatsu A, Shiiba M, Bukawa H, Yokoe H, Tanzawa H, 2006, Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis. Br J Cancer 94: 717–723
Yuan RH, Jeng YM, Chen HL, Lai PL, Pan HW, Hsieh FJ, Lin CY, Lee PH, Hsu HC, 2006, Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 209:549–558
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Chen G,Wang H,Gharib TG, Huang CC, Thomas DG, Shedden KA, Kuick R, Taylor JM, Kardia SL, Misek DE, Giordano TJ, Iannettoni MD, Orringer MB, Hanash SM, Beer DG, 2003, Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. Mol Cell Proteomics 2:107–116
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1013
EP 1020
DI 10.1007/s12253-015-9930-y
PG 8
ER
PT J
AU Wang, XX
Liu, BB
Wu, X
Su, D
Zhu, Z
Fu, L
AF Wang, Xin-Xin
Liu, Bing-Bing
Wu, Xiao
Su, Dan
Zhu, Zhengmao
Fu, Li
TI Loss of Leucine Zipper Putative Tumor Suppressor 1 (LZTS1) Expression Contributes to Lymph Node Metastasis of Breast Invasive Micropapillary Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast IMPC; LZTS1; Gene expression and promoter methylation
ID Breast IMPC; LZTS1; Gene expression and promoter methylation
AB Breast invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer with a high potential of lymph node metastasis, aggressive clinical behavior, and poor disease-free or overall survival. Expression of leucine zipper putative tumor suppressor 1 (LZTS1) was frequently lost or reduced in breast cancer tissues. This study investigated the expression of LZTS1 protein in breast IMPC tissues using immunohistochemistry. In addition, somatic LZTS1 mutations and promoter methylation were assessed to determine an association with clinicopathological data from IMPC patients. LZTS1 protein was downregulated in 62 (62 %) of 100 IMPC tissue samples and was significantly associated with lymph node metastasis (P<0.05). A LZTS1 exon mutation occurred in one of the 53 IMPC cases analyzed, whereas a LZTS1 intron mutation occurred in 26 of 53 cases. Moreover, LZTS1 promoter was frequently methylated in IMPC samples and was associated with reduced LZTS1 expression levels in IMPC tissues. These data demonstrated that the loss of LZTS1 expression was associated with lymph node metastasis in patients with IMPC, and LZTS1 promoter methylation could be responsible for the loss of LZTS1 expression.
C1 [Wang, Xin-Xin] Capital Medical University, Beijing Youan Hospital, Department of Pathology, 100069 Beijing, China.
[Liu, Bing-Bing] Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, Huan Hu Xi Road, 300060 Tianjin, China.
[Wu, Xiao] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 300071 Tianjin, China.
[Su, Dan] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 300071 Tianjin, China.
[Zhu, Zhengmao] Nankai University, College of Life Sciences, Department of Genetics and Cell Biology, 300071 Tianjin, China.
[Fu, Li] Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, Huan Hu Xi Road, 300060 Tianjin, China.
RP Fu, L (reprint author), Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China.
EM tj.lzts1@gmail.com
CR Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, 2011, WHO classification of tumors of the breast. IARC Press, Lyon, pp 14–17
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Nassar H, Wallis T, Andea A, Dey J, Adsay V, Visscher D, 2001, Clinicopathologic analysis of invasive micropapillary differentiation in breast carcinoma. Mod Pathol 14:836–841
Walsh MM, Bleiweiss IJ, 2001, Invasive micropapillary carcinoma of the breast: eighty cases of an underrecognized entity. Hum Pathol 32:583–589
Pettinato G, Manivel CJ, Panico L, Sparano L, Petrella G, 2004, Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. Am J Clin Pathol 121:857–866
Ishii H, Baffa R, Numata SI, Murakumo Y, Rattan S, Inoue H, Mori M, Fidanza V, Alder H, Croce CM, 1999, The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. Proc Natl Acad Sci U S A 96: 3928–3933
Toyooka S, Fukuyama Y, Wistuba II, Tockman MS, Minna JD, Gazdar AF, 2002, Differential expression of FEZ1/LZTS1 gene in lung cancers and their cell cultures. Clin Cancer Res 8:2292–2297
Vecchione A, Ishii H, Shiao YH, Trapasso F, Rugge M, Tamburrino JF, Murakumo Y, Alder H, Croce CM, Baffa R, 2001, Fez1/lzts1 alterations in gastric carcinoma. Clin Cancer Res 7:1546–1552
Vecchione A, Ishii H, Baldassarre G, Bassi P, Trapasso F, Alder H, Pagano F, Gomella LG, Croce CM, Baffa R, 2002, FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells. Am J Pathol 160:1345–1352
Nonaka D, Fabbri A, Roz L, Mariani L, Vecchione A, Moore GW, Tavecchio L, Croce CM, Sozzi G, 2005, Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer. Cancer Res 65: 1207–1212
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Ono K, Uzawa K, Nakatsuru M, Shiiba M, Mochida Y, Tada A, Bukawa H, Miyakawa A, Yokoe H, Tanzawa H, 2003, Downregulation of FEZ1/LZTS1 gene with frequent loss of heterozygosity in oral squamous cell carcinomas. Int J Oncol 23:297–302
Vecchione A, Galetti TP, GardimanM, Ishii H, Giarnieri E, Pagano F, Gomella LG, Croce CM, Baffa R, 2004, Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases.BMC Urol 4:11
Ishii H, Vecchione A, Murakumo Y, Baldassarre G, Numata S, Trapasso F, Alder H, Baffa R, Croce CM, 2001, FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc Natl Acad Sci U S A 98:10374–10379
Chen L, Zhu Z, Sun X, Dong XY,Wei J, Gu F, Sun YL, Zhou J,Dong JT, Fu L, 2009, Down-regulation of tumor suppressor gene FEZ1/ LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis. Breast Cancer Res Treat 116:471–478
Guo X, Chen L, Lang R, Fan Y, Zhang X, Fu L, 2006, Invasive micropapillary carcinoma of the breast: association of pathologic features with lymph node metastasis. Am J Clin Pathol 126:740–746
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Arnold JM, Choong DY, Lai J, Campbell IG, Chenevix-Trench G, 2006, Mutation and expression analysis of LZTS1 in ovarian cancer. Cancer Lett 233:151–157
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Wang XX, Zhu Z, Su D, Lei T, Wu X, Fan Y, Li X, Zhao J, Fu L, Dong JT, Fu L, 2011, Down-regulation of leucine zipper putative tumor suppressor 1 is associated with poor prognosis, increased cell motility and invasion, and pithelial-to-mesenchymal transition characteristics in human breast carcinoma. Hum Pathol 42:1410–1419
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1021
EP 1026
DI 10.1007/s12253-015-9923-x
PG 6
ER
PT J
AU Zavesky, L
Jandakova, E
Turyna, R
Langmeierova, L
Weinberger, V
Zaveska Drabkova, L
Hulkova, M
Horinek, A
Duskova, D
Feyereisl, J
Minar, L
Kohoutova, M
AF Zavesky, Ludek
Jandakova, Eva
Turyna, Radovan
Langmeierova, Lucie
Weinberger, Vit
Zaveska Drabkova, Lenka
Hulkova, Martina
Horinek, Ales
Duskova, Daniela
Feyereisl, Jaroslav
Minar, Lubos
Kohoutova, Milada
TI Evaluation of Cell-Free Urine microRNAs Expression for the Use in Diagnosis of Ovarian and Endometrial Cancers. A Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; Endometrial cancer; Urine; microRNA; miR-92a; miR-106b
ID Ovarian cancer; Endometrial cancer; Urine; microRNA; miR-92a; miR-106b
AB Among gynaecological cancers, epithelial ovarian cancers are the most deadly cancers while endometrial cancers are the most common diseases. Efforts to establish relevant novel diagnostic, screening and prognostic markers are aimed to help reduce the high level of mortality, chemoresistance and recurrence, particularly in ovarian cancer. MicroRNAs, the class of post-transcriptional regulators, have emerged as the promising diagnostic and prognostic markers associated with various diseased states recently. Urine has been shown as the source of microRNAs several years ago; however, there has been lack of information on urine microRNA expression in ovarian and endometrial cancers till now. In this pilot study, we examined the expression of candidate cell-free urine microRNAs in ovarian cancer and endometrial cancer patients using quantitative real-time PCR. We compared the expression between pre- and post-surgery ovarian cancer samples, and between patients with ovarian and endometrial cancers and healthy controls, within three types of experiments. These experiments evaluated three different isolation methods of urine RNA, representing two supernatant and one exosome fractions of extracellular microRNA. In ovarian cancer, we found miR-92a significantly up-regulated, and miR-106b significantly down-regulated in comparison with control samples. In endometrial cancer, only miR-106b was found down-regulated significantly compared to control samples. Using exosome RNA, no significant de-regulations in microRNAs expression could be found in either of the cancers investigated.We propose that more research should now focus on confirming the diagnostic potential of urine microRNAs in gynaecological cancers using more clinical samples and largescale expression profiling methods.
C1 [Zavesky, Ludek] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Institute of Biology and Medical Genetics, Albertov 4, CZ-128 00 Prague, Czech Republic.
[Jandakova, Eva] University Hospital Brno, Department of Pathology, Obilni trh 11, CZ-625 00 Brno, Czech Republic.
[Turyna, Radovan] Institute for the Care of Mother and Child, Podolske nabrezi 157, CZ-147 00 Prague, Czech Republic.
[Langmeierova, Lucie] General University Hospital in Prague, Faculty Transfusion Centre, U Nemocnice 2, CZ-128 08 Prague, Czech Republic.
[Weinberger, Vit] University Hospital Brno, Department of Obstetrics and Gynaecology, Obilni trh 11, CZ-625 00 Brno, Czech Republic.
[Zaveska Drabkova, Lenka] Academy of Sciences of the Czech Republic, Institute of Botany of the ASCR, v. v. i., Zamek 1, CZ-252 43 Prague, Czech Republic.
[Hulkova, Martina] General University Hospital in Prague, Department of Pediatrics and Adolescent Medicine, Ke Karlovu 2, CZ-121 00 Prague, Czech Republic.
[Horinek, Ales] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Institute of Biology and Medical Genetics, Albertov 4, CZ-128 00 Prague, Czech Republic.
[Duskova, Daniela] General University Hospital in Prague, Faculty Transfusion Centre, U Nemocnice 2, CZ-128 08 Prague, Czech Republic.
[Feyereisl, Jaroslav] Institute for the Care of Mother and Child, Podolske nabrezi 157, CZ-147 00 Prague, Czech Republic.
[Minar, Lubos] University Hospital Brno, Department of Obstetrics and Gynaecology, Obilni trh 11, CZ-625 00 Brno, Czech Republic.
[Kohoutova, Milada] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Institute of Biology and Medical Genetics, Albertov 4, CZ-128 00 Prague, Czech Republic.
RP Zavesky, L (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Institute of Biology and Medical Genetics, CZ-128 00 Prague, Czech Republic.
EM ludek.zavesky@gmail.com
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Kan CWS, Hahn MA, Gard GB et al, 2012, Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer. BMC Cancer 12:627., DOI 10.1186/1471-2407- 12-627
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1027
EP 1035
DI 10.1007/s12253-015-9914-y
PG 9
ER
PT J
AU Oshikawa, G
Yoshioka, K
Takahashi, Y
Shingai, N
Ikegawa, Sh
Kobayashil, T
Doki, N
Kakihana, K
Ohashi, K
Sakamaki, H
AF Oshikawa, Gaku
Yoshioka, Kousuke
Takahashi, Yukie
Shingai, Naoki
Ikegawa, Shuntaro
Kobayashil, Takeshi
Doki, Noriko
Kakihana, Kazuhiko
Ohashi, Kazuteru
Sakamaki, Hisashi
TI Impact of prior azacitidine on the outcome of allogeneic hematopoietic transplantation for myelodysplastic syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myelodysplastic syndrome; Allogeneic hematopoietic stem cell transplantation; Azacitidine
ID Myelodysplastic syndrome; Allogeneic hematopoietic stem cell transplantation; Azacitidine
AB To clarify the clinical impact of prior use of azacitidine (AZA) on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS), we retrospectively reviewed the clinical outcomes of 15 MDS patients who were treated with AZA before allo-HSCT (AZA group). We compared the outcomes of these 15 patients with 52 MDS patients who were solely given the best supportive care (BSC) before allo-HSCT (BSC group). Although patients in the AZA group were older with higher International Prognostic Scoring System (IPSS) scores compared to patients in the BSC group, no significant differences were found between the two groups in overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) or non-relapse mortality. However, in patients with a higher IPSS score (Int-2/High), pre-transplant AZA may provide better OS and DFS and lower CIR. Acute graft-versus-host disease rates were similar between the two groups. These results should be reassuring to patients with high-risk MDS receiving AZA before allo-HSCT.
C1 [Oshikawa, Gaku] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Yoshioka, Kousuke] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Takahashi, Yukie] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Shingai, Naoki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ikegawa, Shuntaro] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashil, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Doki, Noriko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Oshikawa, G (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM gaku.oshikawa@gmail.com
CR Gyurkocza B, Deeg HJ, 2012, Allogeneic hematopoietic cell transplantation forMDS: forwhom, when and how? Blood Rev 26:247– 254
Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R et al, 2002, Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20:2429–2440
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A et al, 2009, Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10:223–232
Kim DY, Lee JH, Park YH, Kim SD, Choi Y, Lee SB et al, 2012, Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant 47:374–379
Damaj G, Duhamel A, Robin M, Beguin Y, Michallet M,MohtyM et al, 2012, Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Societe Francaise de Greffe de Moelle et de Therapie-Cellulaire and the Groupe-Francophone des Myelodysplasies. J Clin Oncol 20: 4533–4540
Gerds AT, Gooley TA, Estey EH, Appelbaum FR, Deeg HJ, Scott BL, 2012, Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol Blood Marrow Transplant 18:1211–1218
Field T, Perkins J, Huang Y, Kharfan-DabajaMA, Alsina M, Ayala E et al, 2010, 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 45: 255–260
Cogle CR, Imanirad I, Wiggins LE, Hsu J, Brown R, Scornik JC et al, 2010, Hypomethylating agent induction therapy followed by hematopoietic cell transplantation is feasible in patients with myelodysplastic syndromes. Clin Adv Hematol Oncol 8:40– 46
Yahng SA, Yoon JH, Shin SH, Lee SE, Cho BS, Lee DG et al, 2013, Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes. Eur J Haematol 90:111–120
Damaj G, Duhamel A, Robin M, Milpied N, Michallet M, Chevallier P et al, 2013, Azacitidine versus best supportive care before non-myeloablative allogeneic stem cell transplantation for MDS: a study by the SFGM-TC. Leukemia Res 37(Suppl 1):S14– S15
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B,Wijermans PW, Nimer SD et al, 2006, Clinical application and proposal for modification of the International Working Group, IWG, response criteria in myelodysplasia. Blood 108:419–425
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Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al, 1997, International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088
Giralt S, 2005, Reduced-intensity conditioning regimens for hematologic malignancies: what have we learned over the last 10 years? Hematol Am Soc Hematol Educ Program 2005:384–389
Kanda Y, 2013, Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458
NCCN, 2012, Clinical practice guidelines in oncology: Myelodysplastic syndromes version 2.2014. National Comprehensive Cancer Network, Washington
Sanchez-Abarca LI, Gutierrez-Cosio S, Santamaria C, Caballero- Velazquez T, Blanco B, Herrero-Sanchez C et al, 2010, Immunomodulatory effect of 5-azacytidine, 5-azaC): potential role in the transplantation setting. Blood 115:107–121
Choi J, Ritchey J, Prior JL, Holt M, Shannon WD, Deych E et al, 2010, In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood 116:129–139
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1037
EP 1043
DI 10.1007/s12253-015-9933-8
PG 7
ER
PT J
AU Marrero-Rodriguez, D
Taniguchi-Ponciano, K
Lopez-Sleman, J
Romero-Morelos, P
Mendoza-Rodriguez, M
Garcia, I
Huerta-Padilla, V
Mantilla, A
Duarte, A
Pina, P
Rodriguez-Esquivel, M
Lopez-Romero, R
Parrazal-Romero, J
Tobias-Alonso, S
Jimenez-Vega, F
Alvarez-Blanco, M
Salcedo, M
AF Marrero-Rodriguez, Daniel
Taniguchi-Ponciano, Keiko
Lopez-Sleman, Julio
Romero-Morelos, Pablo
Mendoza-Rodriguez, Monica
Garcia, Israel
Huerta-Padilla, Victor
Mantilla, Alejandra
Duarte, Armando
Pina, Patricia
Rodriguez-Esquivel, Miriam
Lopez-Romero, Ricardo
Parrazal-Romero, Jorge
Tobias-Alonso, Salvador
Jimenez-Vega, Florinda
Alvarez-Blanco, Mario
Salcedo, Mauricio
TI Thymopoietin Beta and Gamma Isoforms as a Potential Diagnostic Molecular Marker for Breast Cancer: Preliminary Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thymopoietin; Isoforms; Molecular marker; Breast cancer
ID Thymopoietin; Isoforms; Molecular marker; Breast cancer
AB Thymopoietin (TMPO) is an inner nuclear membrane protein, the coding gene named equally, can give arise to six isoforms by alternative splicing. This gene has been found up regulated in several types of cancer. At present work, we evaluated the TMPO isoforms generated by alternative splicing as well as the protein signal detection in breast cancer samples. TMPO expression was analyzed by immunohistochemistry in tissue microarray containing 46 breast tissue samples including normal (n=6), benign lesions (n=18) (fibroadenomas (n=6), fibrocystic changes (n=6), ductal hyperplasias (n=6)) and breast carcinoma (n=22). Isoforms -α, −β and -γ of TMPO were evaluated using RT-PCR; clinical-pathological correlation analysis were done by mean of X2. Neither the normal nor the benign lesions of the breas t showed positive TMPO immunodetection, whilst 45 % of the breast carcinomas were immunopositive (p=0.000), nine of ten positives carcinomas correspond to the Luminal A subtype. Further, alpha isoform was present in all breast samples analyzed; however, beta and gamma isoforms were only present in ten (p=0.003) and 17 (p=0.000), respectively, in the breast cancer samples. According with the present data, we suggest that TMPOβ and -γ isoforms could provide a potential reliable diagnostic marker for breast cancer.
C1 [Marrero-Rodriguez, Daniel] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Taniguchi-Ponciano, Keiko] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Lopez-Sleman, Julio] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Romero-Morelos, Pablo] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Mendoza-Rodriguez, Monica] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Garcia, Israel] Hospital de Oncologia CMN-SXXI, IMSS, Servicio de Ginecologia OncologicaMexico City, Mexico.
[Huerta-Padilla, Victor] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Mantilla, Alejandra] Hospital de Oncologia CMN-SXXI, IMSS, Servicio de PatologiaMexico City, Mexico.
[Duarte, Armando] Hospital General de Zona #35, IMSS, Cd. Juarez, Clinica de MamaChihuahua, Mexico.
[Pina, Patricia] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Rodriguez-Esquivel, Miriam] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Lopez-Romero, Ricardo] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Parrazal-Romero, Jorge] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
[Tobias-Alonso, Salvador] Hopital General, Cd. Juarez, Departamento de PatologiaChihuahua, Mexico.
[Jimenez-Vega, Florinda] Universidad Autonoma de Ciudad Juarez, Laboratorio de BiotecnologiaChihuahua, Mexico.
[Alvarez-Blanco, Mario] Hospital General de Mexico, S.S., Servicio de Oncologia, Unidad de QuimioterapiaMexico City, Mexico.
[Salcedo, Mauricio] Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, Av. Cuauhtemoc 330, Col. Doctores, DF 06720 Mexico City, Mexico.
RP Salcedo, M (reprint author), Hospital de Oncologia CMN-SXXI. IMSS, Unidad de Investigacion Medica en Enfermedades Oncologicas, Laboratorio de Oncologia genomica, DF 06720 Mexico City, Mexico.
EM maosal89@yahoo.com
CR Knaul FM, Nigenda B, Lozano R, Arreola H, Langer A, Frenk J, 2008, Breast cancer in Mexico: a pressing priority. Reprod Health Matters 16:113–123
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1045
EP 1050
DI 10.1007/s12253-015-9907-x
PG 6
ER
PT J
AU Lakosi, F
Gulyban,
Janvary, ZsL
Simoni, BMS
Jansen, N
Seidel, L
Kovacs,
Vavassis, P
Coucke, P
AF Lakosi, Ferenc
Gulyban, Akos
Janvary, Zsolt Levente
Simoni, Ben-Mustapha Selma
Jansen, Nicolas
Seidel, Laurence
Kovacs, Arpad
Vavassis, Peter
Coucke, Philippe
TI Respiratory Motion, Anterior Heart Displacement and Heart Dosimetry: Comparison Between Prone (Pr) and Supine (Su) Whole Breast Irradiation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Prone breast radiotherapy; 4D-computed tomography; Respiratory motion; Left-anterior-descending coronary artery
ID Breast cancer; Prone breast radiotherapy; 4D-computed tomography; Respiratory motion; Left-anterior-descending coronary artery
AB To analyze respiratory motion of surgical clips, chest wall (CW) and the anterior displacement of the heart and its impact on heart dosimetry between prone (Pr) and supine (Su) positions during whole breast radiotherapy after breast conserving surgery. Sixteen patients underwent 4D-CT for radiotherapy planning in Pr and Su positions. Maximum inhale and maximum exhale phases were analyzed. Mean 3D vectorial displacements±standard deviations (SD) of the surgical clips were measured. Volumetric changes of the CW were recorded and compared. Cardiac displacement was assessed by a volume between the inner surface of CW and the myocardium of the heart (CW/H-V). For left-sided cases, comparative dosimetry was performed in each position simulating no- (Pr-noC, Su-noC) versus daily correction protocols (Pr-C, Su-C). The movements of 81 surgical clips were analyzed. Prone positioning significantly reduced both the mean 3D vectorial displacements (1.1±0.6 (Pr) vs. 2.0±0.9 mm (Su), p<0.01) and their variability (0.3±0.2 vs. 0.5±0.3 mm, p=0.01). Respiration-induced volumetric changes of CW were also significantly lower in Pr (2.3±4.9 vs. 9.6± 7.1 cm3 , p<0.01). The CW/H-V was significantly smaller in Pr than in Su (39.9±14.6 vs. 64.3±28.2 cm3 , p<0.01). Besides identical target coverage heart, left-anterior-descending coronary artery (LADCA) and ipsilateral lung dose parameters were lowered with Pr-C compared to Pr-noC, Su-C and Su-noC. Prone position significantly reduced respirationrelated surgical clip movements, their variability as well as CW movements. Significant anterior heart displacement was observed in Pr. Prone position with daily online correction could maximize the heart and LADCA protection.
C1 [Lakosi, Ferenc] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
[Gulyban, Akos] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
[Janvary, Zsolt Levente] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
[Simoni, Ben-Mustapha Selma] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
[Jansen, Nicolas] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
[Seidel, Laurence] University Hospital of Liege, Department of BiostatisticsLiege, Belgium.
[Kovacs, Arpad] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Vavassis, Peter] Hopital Maisonneuve- RosemontQuebec, Canada.
[Coucke, Philippe] University Hospital of Liege, Department of Radiation Oncology, Avenue de l’hopital, B.35, 4000 Liege, Belgium.
RP Lakosi, F (reprint author), University Hospital of Liege, Department of Radiation Oncology, 4000 Liege, Belgium.
EM lakosiferenc@yahoo.com;flakosi@chu.ulg.ac.be
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1051
EP 1058
DI 10.1007/s12253-015-9932-9
PG 8
ER
PT J
AU Erdelyi-Belle, B
Torok, Gy
Apati,
Sarkadi, B
Schaff, Zs
Kiss, A
Homolya, L
AF Erdelyi-Belle, Boglarka
Torok, Gyorgy
Apati, Agota
Sarkadi, Balazs
Schaff, Zsuzsa
Kiss, Andras
Homolya, Laszlo
TI Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human embryonic stem cells; Stem cell differentiation; Cytokeratins; Tight junctions; Claudins; Tricellulin; Agrin
ID Human embryonic stem cells; Stem cell differentiation; Cytokeratins; Tight junctions; Claudins; Tricellulin; Agrin
AB Human embryonic stem cells can be differentiated in vitro into a wide variety of progeny cells by addition of different morphogens and growth factors. Our aim was to monitor the expression pattern of tight junction (TJ) components and various cellular markers during differentiation of stem cell lines toward the hepatic lineage. Human embryonic stem cell lines (HUES1, HUES9) were differentiated into endoderm-like cells, and further differentiated to hepatocytelike cells. Gene expressions of Oct3/4, Nanog, alpha-fetoprotein, albumin, cytokeratins (CK-7, CK-8, CK-18, CK-19), ATP-binding cassette (ABC) transporters (ABCC2, ABCC7, ABCG2), and various TJ components, including claudin-1, claudin-4, claudin-5, claudin-7, and tricellulin, as well as an extracellular matrix component, agrin were monitored during hepatic differentiation by real-time quantitative PCR. The differentiated cells exhibit epithelial morphology and functional assessments similar to that of hepatocytes. The expression level of stem cell marker genes (Oct3/4 and Nanog) significantly and gradually decreased, while liver-associated genes (alpha-fetoprotein, albumin) reached their highest expression at the end of the differentiation. The endoderm-like cells expressed claudin-1, which declined eventually. The expression levels of cholangiocyte markers including claudin-4, CK-7, CK-19, and agrin gradually increased and reached their highest level at the final stage of differentiation. In contrast, these cells did not express notable level of claudin- 7, CK-8 and tricellulin. The marker set used for monitoring differentiation revealed both hepatocyte and cholangiocyte characteristics of the differentiated cells at the final stage. This is the first report describing the expression level changes of various TJ components, and underlining their importance in hepatic differentiation.
C1 [Erdelyi-Belle, Boglarka] Semmelweis University, 2nd Department of Pathology, Ulloi Street 93, 1091 Budapest, Hungary.
[Torok, Gyorgy] Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzymology, Magyar tudosok korutja 2, 1117 Budapest, Hungary.
[Apati, Agota] Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzymology, Magyar tudosok korutja 2, 1117 Budapest, Hungary.
[Sarkadi, Balazs] Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzymology, Magyar tudosok korutja 2, 1117 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi Street 93, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi Street 93, 1091 Budapest, Hungary.
[Homolya, Laszlo] Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzymology, Magyar tudosok korutja 2, 1117 Budapest, Hungary.
RP Homolya, L (reprint author), Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzymology, 1117 Budapest, Hungary.
EM homolya.laszlo@ttk.mta.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1059
EP 1070
DI 10.1007/s12253-015-9936-5
PG 12
ER
PT J
AU Carmignani, L
Macchi, A
Ratti, D
Finkelberg, E
Casellato, S
Bozzini, G
Maruccia, S
Marenghi, C
Picozzi, S
AF Carmignani, Luca
Macchi, Alberto
Ratti, Dario
Finkelberg, Elisabetta
Casellato, Stefano
Bozzini, Giorgio
Maruccia, Serena
Marenghi, Carlo
Picozzi, Stefano
TI Are Histological Findings of Thulium Laser Vapo-Enucleation Versus Transurethral Resection of the Prostate Comparable?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate; Benign prostatic hypertrophy; Transurethral; Thulium; Laser
ID Prostate; Benign prostatic hypertrophy; Transurethral; Thulium; Laser
AB We investigated if an adequate histological diagnosis can be made from tissue after Thulium laser vapoenucleation of the prostate (ThuVEP) and whether it is comparable to transurethral prostate resection (TURP) tissue findings in patients with symptomatic benign prostatic hyperplasia. We analyzed 350 ThuLEP and 100 matched TURP tissue specimens from patients who underwent one of the two procedures between January 2009 and June 2014. Thulium Laser Enucleation of Prostate (ThuVEP) was combined with mechanical morcellation of the resected lobe. Each histological specimen was reviewed by two pathologists. Preoperative prostate ultrasound volume, total serum prostatic specific antigen and postoperative tissue weight were evaluated. Microscopic histological diagnosis was assessed by standard histological techniques and immunohistochemical evaluation. Patients were comparable in terms of age and preoperative total serum prostate specific antigen. Incidental adenocarcinoma and high grade PIN of the prostate were diagnosed in a comparable percent of specimens in the 2 groups (2.5 % in the ThuVEP group versus 3 % in the TURP group). Tissue thermal artifacts induced by the Thulium laser are mostly due to coagulation as that of the conventional monopolar diathermy in TURP. Tissue quality was maintained in the ThuVEP histological specimens. Tissue maintain histological characteristics and proprieties without modification for successive immunoistochemical analysis. The pathologist ability to detect incidental prostate cancer and PIN was maintained even if there is a quoted of vaporized tissue.
C1 [Carmignani, Luca] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Macchi, Alberto] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Ratti, Dario] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Finkelberg, Elisabetta] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Casellato, Stefano] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Bozzini, Giorgio] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Maruccia, Serena] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Marenghi, Carlo] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
[Picozzi, Stefano] IRCCS Policlinico San Donato, University of Milan, Urology Department, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy.
RP Picozzi, S (reprint author), IRCCS Policlinico San Donato, University of Milan, Urology Department, 20097 San Donato Milanese, Italy.
EM stepico@tin.it
CR Suhani, Gupta S, Gupta A, Saha S, Mahapatra L, Srivastava U, 2013, Outcome of surgery for benign prostatic hyperplasia-is it predictable? J Clin Diagn Res 7:2859–2862
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1071
EP 1075
DI 10.1007/s12253-015-9931-x
PG 5
ER
PT J
AU Liu, P
Jiang, W
Ren, H
Zhang, H
Hao, J
AF Liu, Pengfei
Jiang, Wenhua
Ren, He
Zhang, Huilai
Hao, Jihui
TI Exploring the Molecular Mechanism and Biomakers of Liver Cancer Based on Gene Expression Microarray
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liver cancer; Bioinformatics; Biomarker; Pathway
ID Liver cancer; Bioinformatics; Biomarker; Pathway
AB Liver cancer is one of the most common cancers worldwide with high morbidity and mortality. Its molecular mechanism hasn’t been fully understood though many studies have been conducted and thus further researches are still needed to improve the prognosis of liver cancer. Firstly, differentially expressed genes (DEGs) between six Mdr2-knockout (Mdr2- KO) mutant mice samples (3-month-old and 12-month-old) and six control mice samples were identified. Then, the enriched GO terms and KEGG pathways of those DEGs were obtained using the Database for Annotation, Visualization and Integrated Discovery (DAVID, http://david.abcc.ncifcrf.gov/). Finally, protein-protein interactions (PPI) network of those DEGs were constructed using STRING database (http://www.string-db.org/) and visualized by Cytoscape software, at the same time, genes with high degree were selected out. Several novel biomarkers that might play important roles in liver cancer were identified through the analysis of gene microarray in GEO. Also, some genes such as Tyrobp, Ctss and pathways such as Pathways in cancer, ECM-receptor interaction that had been researched previously were further confirmed in this study. Through the bioinformatics analysis of the gene microarray in GEO, we found some novel biomarkers of liver cancer and further confirmed some known biomarkers.
C1 [Liu, Pengfei] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and LeukemiaTianjin, China.
[Jiang, Wenhua] The Second Hospital of Tianjin Medical University, Department of RadiotherapyTianjin, China.
[Ren, He] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic CancerTianjin, China.
[Zhang, Huilai] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and LeukemiaTianjin, China.
[Hao, Jihui] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic CancerTianjin, China.
RP Hao, J (reprint author), National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer, Tianjin, China.
EM haojihui@tjmuch.com
CR Bertino G, Demma S, Ardiri A, Proiti M, Gruttadauria S, Toro A, Malaguarnera G, Bertino N, Malaguarnera M, Di Carlo I, 2014, Hepatocellular carcinoma: novel molecular targets in carcinogenesis for future therapies. Biomed Res Int 2014, 203693
JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S, 2014, GOLP3 is a predictor of survival in patients with hepatocellular carcinoma. Clin Invest Med 37(4):E233
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Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Barash H, Domany E, Galun E, Goldenberg D, 2007, Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice. Mol Cancer Ther 6(4): 1283–1291
Yang YM, Lee WH, Lee CG, An J, Kim ES, Kim SH, Lee SK, Lee CH, Dhanasekaran DN, Moon A, Hwang S, Lee SJ, Park JW, Kim KM, Kim SG, 2014, Galpha gep oncogene deregulation of p53- responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma. Oncogene 0
Xu X, Huang P, Yang B, Wang X, Xia J, 2014, Roles of CXCL5 on migration and invasion of liver cancer cells. J Transl Med 12:193
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Gautier L, Cope L, Bolstad BM, Irizarry RA, 2004, Affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3): 307–315
Diboun I, Wernisch L, Orengo CA, Koltzenburg M, 2006, Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics 7:252
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Shabo I, Olsson H, Stal O, Svanvik J, 2013, Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival. Clin Breast Cancer 13(5):371–377
Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, Rodrigues A, Magalhaes JS, Oliveira J, Lothe RA, Teixeira MR, Jeronimo C, Lind GE, 2010, Three epigenetic biomarkers, GDF15, TMEFF2, and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin Cancer Res 16(23):5842–5851
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1077
EP 1083
DI 10.1007/s12253-015-9926-7
PG 7
ER
PT J
AU Cates, MMJ
AF Cates, M M Justin
TI Prognostic factors for second recurrence after surgical resection of recurrent desmoid-type fibromatosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aggressive fibromatosis; Local recurrence; Prognosis; Second recurrence
ID Aggressive fibromatosis; Local recurrence; Prognosis; Second recurrence
AB The optimal management of recurrent desmoidtype fibromatosis is undefined. This study was performed to determine what factors, if any, predict second recurrence after surgical resection of recurrent desmoid tumors. Of 41 patients with recurrent desmoid-type fibromatosis, 29 underwent surgical resection and 8 were followed by observation. Four others received adjuvant chemo/pharmacotherapy. Clinicopathologic features were assessed as prognostic factors for second recurrence after surgical resection of recurrent desmoid tumors by Cox proportional hazards regression. Nine of 29 patients who underwent surgical resection of recurrent desmoid tumor developed a second recurrence. Larger size of recurrent tumor was associated with increased risk of second recurrence (hazard ratio, 1.09; P=0.006). Treatment of the primary tumor with adjuvant radiation therapy also increased risk of re-recurrence (3.41; P=0.032). Second recurrence of desmoid-type fibromatosis after surgical resection is, much like recurrence of primary desmoid tumor, difficult to predict with current prognostic indicators.
C1 [Cates, M M Justin] Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, CC-3322, 1161 21st Ave. South, 37232 Nashville, TN, USA.
RP Cates, MMJ (reprint author), Vanderbilt University Medical Center and Vanderbilt University, School of Medicine, Department of Pathology, 37232 Nashville, USA.
EM justin.m.cates@vanderbilt.edu
CR National Comprehensive Cancer Network Soft Tissue Sarcoma, Version 2.2014). http://www.Nccn.Org/Professionals/Physician_ Gls/Pdf/Sarcoma.Pdf. Accessed 20 March 2014
Ballo MT, Zagars GK, Pollack A, Pisters PW, Pollack RA, 1999, Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy. J Clin Oncol 17:158–167
Lev D, Kotilingam D, Wei C, Ballo MT, Zagars GK, Pisters PW, Lazar AA, Patel SR, Benjamin RS, Pollock RE, 2007, Optimizing treatment of desmoid tumors. J Clin Oncol 25:1785–1791
Gluck I, Griffith KA, Biermann JS, Feng FY, Lucas DR, Ben-Josef E, 2011, Role of radiotherapy in the management of desmoid tumors. Int J Radiat Oncol Biol Phys 80:787–792
Prodinger PM, Rechl H, Keller M, Pilge H, Salzmann M, Von Eisenhart-Rothe R, Holzapfel BM, 2013, Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre. Int Orthop 37:1987–1993
Mullen JT, Delaney TF, Kobayashi WK, Szymonifka J, Yeap BY, Chen YL, Rosenberg AE, Harmon DC, Choy E, Yoon SS, Raskin KA, Nielsen GP, Hornicek FJ, 2012, Desmoid tumor: analysis of prognostic factors and outcomes in a surgical series. Ann Surg Oncol 19:4028–4035
Nuyttens JJ, Rust PF, Thomas CR Jr, Turrisi AT, 2000, Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: a comparative review of 22 articles. Cancer 88: 1517–1523
Bonvalot S, Eldweny H, Haddad V, Rimareix F, Missenard G, Oberlin O, Vanel D, Terrier P, Blay JY, Le Cesne A, Le Pechoux C, 2008, Extra-abdominal primary fibromatosis: aggressive management could be avoided in a subgroup of patients. Eur J Surg Oncol 34:462–468
Gronchi A, Casali PG, Mariani L, Lo Vullo S, Colecchia M, Lozza L, Bertulli R, Fiore M,Olmi P, SantinamiM, Rosai J, 2003, Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution. J Clin Oncol 21:1390–1397
Peng PD, Hyder O, Mavros MN, Turley R, Groeschl R, Firoozmand A, Lidsky M, Herman JM, Choti M, Ahuja N, Anders R, Blazer DG III, Gamblin TC, Pawlik TM, 2012, Management and recurrence patterns of desmoids tumors: a multi-institutional analysis of 211 patients. Ann Surg Oncol 19: 4036–4042
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Cates JM, Stricker TP, 2014, Surgical resection margins in desmoid-type fibromatosis: a critical reassessment. Am J Surg Pathol 38:1707–1714
Crago AM, Denton B, Salas S, Dufresne A, Mezhir JJ, Hameed M, Gonen M, Singer S, Brennan MF, 2013, A prognostic nomogram for prediction of recurrence in desmoid fibromatosis. Ann Surg 258: 347–353
Cates JM, Stricker TP, Sturgeon D, Coffin CM, 2014, Desmoidtype fibromatosis-associated gardner fibromas: prevalence and impact on local recurrence. Cancer Lett 353:176–181
Salas S, Dufresne A, Bui B, Blay JY, Terrier P, Ranchere-Vince D, Bonvalot S, Stoeckle E, Guillou L, Le Cesne A, Oberlin O, Brouste V, Coindre JM, 2011, Prognostic factors influencing progressionfree survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation. J Clin Oncol 29:3553–3558
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1085
EP 1090
DI 10.1007/s12253-015-9939-2
PG 6
ER
PT J
AU Lerant, G
Sarkozy, P
Takacsi-Nagy, Z
Polony, G
Tamas, L
Toth, E
Boer, A
Javor, L
Godeny, M
AF Lerant, Gergely
Sarkozy, Peter
Takacsi-Nagy, Zoltan
Polony, Gabor
Tamas, Laszlo
Toth, Erika
Boer, Andras
Javor, Laszlo
Godeny, Maria
TI Dynamic Contrast-Enhanced MRI Parameters as Biomarkers in Assessing Head and Neck Lesions After Chemoradiotherapy Using a Wide-Bore 3 Tesla Scanner
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DCE-MRI; Head-and neck tumors; Post-treatment imaging; Chemoradiotherapy; Time intensity curve; Biomarker
ID DCE-MRI; Head-and neck tumors; Post-treatment imaging; Chemoradiotherapy; Time intensity curve; Biomarker
AB Pilot studies have shown promising results in characterizing head and neck tumors (HNT) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), differentiating between malignant and benign lesions and evaluating changes in response to chemoradiotherapy (CRT). Our aim was to find DCE-MRI parameters, biomarkers in evaluating the post-CRT status. Two hundred and five patients with head and neck lesions were examined with DCE-MRI sequences. The time intensity curves (TIC) were extracted and processed to acquire time-to-peak (TTP), relative maximum enhancement (RME), relative wash-out (RWO), and two new parameters attack and decay. These parameters were analyzed using univariate tests in SPSS (Statistical Package for the Social Sciences, version 17, SPSS Inc. Chicago, USA) to identify parameters that could be used to infer tumor malignancy and post-CRT changes. Multiple parameters of curve characteristics were significantly different between malignant tumors after CRT (MACRT) and changes caused by CRT. The best-performing biomarkers were the attack and the decay. We also found multiple significant (p<0.05) parameters for both the benign and malignant status as well as pre- and post-CRT status. Our large cohort of data supports the increasing role of DCE-MRI in HNT differentiation, particularly for the assessment of post-CRT status along with accurate morphological imaging.
C1 [Lerant, Gergely] National Institute of Oncology, Center of Radiology, Rath Gyorgy Street 7-9, 1122 Budapest, Hungary.
[Sarkozy, Peter] Budapest University of Technology, Department of Measurement and Information systemsBudapest, Hungary.
[Takacsi-Nagy, Zoltan] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Polony, Gabor] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Tamas, Laszlo] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Boer, Andras] National Institute of Oncology, Multidisciplinary Center of Head and Neck OncologyBudapest, Hungary.
[Javor, Laszlo] National Institute of Oncology, Center of Radiology, Rath Gyorgy Street 7-9, 1122 Budapest, Hungary.
[Godeny, Maria] National Institute of Oncology, Center of Radiology, Rath Gyorgy Street 7-9, 1122 Budapest, Hungary.
RP Lerant, G (reprint author), National Institute of Oncology, Center of Radiology, 1122 Budapest, Hungary.
EM lerger@freemail.hu
CR Furukawa M, Parvathaneni U, Maravilla K, Richards TL, Anzai Y, 2013, Dynamic contrast-enhanced MR perfusion imaging of head and neck tumors at 3 Tesla. Head Neck 35:923–929
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Kim S, Loevner LA, Quon H, Kilger A, Sherman E, Weinstein G, Chalian A, Poptani H, 2010, Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging. AJNR Am J Neuroradiol 31:262–268
Godeny M, 2014, Prognostic factors in advanced pharyngeal and oral cavity cancer; significance of multimodality imaging in terms of 7th edition of TNM. Cancer Imaging 14:1–13
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Hermans R, De Keyzer F, Vandecaveye V, Carp L, 2012, Head and neck cancer imaging. Springer, Berlin/Heidelberg, Germany
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Andrade RS, Heron DE, Degirmenci B, Filho PA, Branstetter BF, Seethala RR, Ferris RL, Avril N, 2006, Posttreatment assessment of response using FDG-PET/CT for patients treated with definitive radiation therapy forhead and neck cancers. Int J Radiat Oncol Biol Phys 65:1315–1322
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Vandecaveye V, de Keyzer F, Vander Poorten V, Deraedt K, Alaerts H, LanduytW, Nuyts S, Hermans R, 2006, Evaluation of the larynx for tumour recurrence by diffusion-weighted MRI after radiotherapy: initial experience in four cases. Br J Radiol 79:681–687
Vandecaveye V, De Keyzer F, Nuyts S, Deraedt K, Dirix P, Hamaekers P, Vander Poorten V, Delaere P, Hermans R, 2007, Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after, chemo, radiotherapy: correlation between radiologic and histopathologic findings. Int J Radiat Oncol Biol Phys 67:960–971
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1091
EP 1099
DI 10.1007/s12253-015-9942-7
PG 9
ER
PT J
AU Zidi, S
Sghaier, I
Zouidi, F
Benahmed, A
Stayoussef, M
Kochkar, R
Gazouani, E
Mezlini, A
Yacoubi-Loueslati, B
AF Zidi, Sabrina
Sghaier, Ikram
Zouidi, Ferjeni
Benahmed, Amira
Stayoussef, Mouna
Kochkar, Radhia
Gazouani, Ezzedine
Mezlini, Amel
Yacoubi-Loueslati, Besma
TI Interleukin-1 Gene Cluster Polymorphisms and its Haplotypes may Predict the Risk to Develop Cervical Cancer in Tunisia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Polymorphism; Haplotype; Interleukin-1beta; Interleukin-1alpha; Interleukin-1receptor antagonist; Cervical cancer; Tunisians
ID Polymorphism; Haplotype; Interleukin-1beta; Interleukin-1alpha; Interleukin-1receptor antagonist; Cervical cancer; Tunisians
AB Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p=0.048; OR= 2.92; 95 % CI=1.00–8.74), moreover, the L/2* decreased the risk (p=0.011; OR=0.47; 95 % CI=0.25–0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β- 511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p=0.030; OR=0.46; 95 % CI=0.22–0.96) (p=0.020; OR=0.68; 95 % CI=0.48–0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p=0.023; OR=0.29; 95 % CI=0.08–0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p=0.032; OR=0.53; 95 % CI=0.29–0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p=0.018; OR=1.57; 95%CI=1.07–2.30).Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Sghaier, Ikram] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Zouidi, Ferjeni] Habib Bourguiba UniversitySfax, Tunisia.
[Benahmed, Amira] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Stayoussef, Mouna] University of Monastir, Faculty of Pharmacy, Research Unit of Hematological and Autoimmune DiseasesMonastir, Tunisia.
[Kochkar, Radhia] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Gazouani, Ezzedine] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Yacoubi-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1101
EP 1107
DI 10.1007/s12253-015-9941-8
PG 7
ER
PT J
AU Vuletic, A
Jovanic, I
Jurisic, V
Milovanovic, Z
Nikolic, S
Spurnic, I
Konjevic, G
AF Vuletic, Ana
Jovanic, Irena
Jurisic, Vladimir
Milovanovic, Zorka
Nikolic, Srdan
Spurnic, Igor
Konjevic, Gordana
TI Decreased Interferon γ Production in CD3+ and CD3−CD56+ Lymphocyte Subsets in Metastatic Regional Lymph Nodes of Melanoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Regional lymph nodes; Interferon γ; T cells; NK cells
ID Regional lymph nodes; Interferon γ; T cells; NK cells
AB As lymphogenic dissemination is very common in melanoma, regional lymph nodes (LN)s represent first immunological barriers to tumor invasion and play a complex role in antitumor immune defense. In this sense, their most prominent role is the presentation of tumor-derived antigens to naive T cells and generation of cell-mediated adaptive immune response. Since tumor micro-environment affects immune cell function in this study we have evaluated the ability of T cells and NK cells in metastatic (involved) and non-metastatic regional LNs to produce interferon γ (IFNγ), a pleiotropic cytokine that regulates adaptive antitumor immune response. Our results show reduced IFNγ production in both T and NK lymphocyte subsets and decreased prevalence of T cells in metastatic regional LNs of melanoma patients. The decrease of IFNγ production in T cells was more pronounced with increased number of involved regional LNs indicating tumor-induced functional impairment of both T and NK cell lymphocyte subsets in involved regional LNs. Therefore, shown low IFNγ production in metastatic LNs may represent an obstacle in adaptive cell-mediated antitumor immune response and hence may enable tumor progression.
C1 [Vuletic, Ana] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
[Jovanic, Irena] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
[Jurisic, Vladimir] University of Kragujevac, Faculty of MedicineKragujevac, Serbia.
[Milovanovic, Zorka] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
[Nikolic, Srdan] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
[Spurnic, Igor] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
[Konjevic, Gordana] Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
RP Vuletic, A (reprint author), Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
EM radovanovica@ncrc.ac.rs
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1109
EP 1114
DI 10.1007/s12253-015-9938-3
PG 6
ER
PT J
AU Lorincz, T
Jemnitz, K
Kardon, T
Mandl, J
Szarka, A
AF Lorincz, Tamas
Jemnitz, Katalin
Kardon, Tamas
Mandl, Jozsef
Szarka, Andras
TI Ferroptosis is Involved in Acetaminophen Induced Cell Death
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acetaminophen; Hepatotoxicity; Ferroptosis; Necroptosis; Glutathione
ID Acetaminophen; Hepatotoxicity; Ferroptosis; Necroptosis; Glutathione
AB The recently described form of programmed cell death, ferroptosis can be induced by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly shows distinct morphologic, biochemical and genetic features from apoptosis, necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely applied analgesic and antipyretic, acetaminophen induces a cell death which can be characterized by GSH depletion, GPX inhibition and caspase independency the involvement of ferroptosis in acetaminophen induced cell death has been investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate the viability of acetaminophen treated HepG2 cells. It should be noticed that these cells do not form NAPQI due to the lack of phase I enzyme expression therefore GSH depletion cannot be observed. However in the case of acetaminophen treated primary mouse hepatocytes the significant elevation of cell viability could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1 treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1 has no influence on the expression of CYP2E1 or on the cellular GSH level which suggest that the protective effect of ferrostatin-1 in APAP induced cell death is not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI conjugation by cellular GSH. Our results suggest that beyond necroptosis and apoptosis a third programmed cell death, ferroptosis is also involved in acetaminophen induced cell death in primary hepatocytes.
C1 [Lorincz, Tamas] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
[Jemnitz, Katalin] Research Centre for Natural Sciences, Hungarian Academy of Sciences, Institute of Molecular PharmacologyBudapest, Hungary.
[Kardon, Tamas] Hungarian Academy of Sciences and Semmelweis University, Pathobiochemistry Research Group, 1444 Budapest, Hungary.
[Mandl, Jozsef] Hungarian Academy of Sciences and Semmelweis University, Pathobiochemistry Research Group, 1444 Budapest, Hungary.
[Szarka, Andras] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
RP Szarka, A (reprint author), Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, 1111 Budapest, Hungary.
EM szarka@mail.bme.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1115
EP 1121
DI 10.1007/s12253-015-9946-3
PG 7
ER
PT J
AU Byatnal, AA
Byatnal, A
Sen, S
Guddattu, V
Solomon, ChM
AF Byatnal, Amit Aditi
Byatnal, Amit
Sen, Subhalakshmi
Guddattu, Vasudev
Solomon, Charlotte Monica
TI Cyclooxygenase-2 – An Imperative Prognostic Biomarker in Oral Squamous Cell Carcinoma- An Immunohistochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoma; Squamous cell; Cyclooxygenase 2; Immunohistochemistry
ID Carcinoma; Squamous cell; Cyclooxygenase 2; Immunohistochemistry
AB Oral squamous cell carcinoma (OSCC) is the most common head and neck squamous cell carcinoma (HNSCC) with metastasis and tumor recurrence resulting in 90 % of cancer associated mortality. COX-2, an inflammatory biomarker, has been shown to play a significant role in tumorigenesis of OSCC. To study the expression of COX-2 in OSCC by immunohistochemistry and investigate its association with the clinicopathological parameters including patient survival. A cross sectional study was carried out in 75 histologically confirmed cases of OSCC. COX-2 expression was evaluated by indirect streptavidin biotin method. The expression was semi-quantitatively assessed using established criteria. The expression profile of COX-2 was correlated with the clinicopathological details like tumor size, regional lymphnode metastasis, distant metastasis, clinical stage, local recurrence of tumor, histological grade, and survival of patient. Chi square and Kaplan Meier statistical tests were applied for assessing this association. COX-2 expression was absent in normal oral mucosa. Over expression of COX-2 was seen in 58 out of 75 specimens of OSCC. Overexpression of COX-2 was significantly associated with the lymphnode involvement, histological grade, local recurrence of tumor and patient survival. COX-2 expression represents an important biomarker of prognostic significance that may be used to identify a subset of patients at high risk and to predict patient survival.
C1 [Byatnal, Amit Aditi] Oral Pathology and MicrobiologyHubli, Karnataka, India.
[Byatnal, Amit] AMES Dental College and Hospital, Department of Oral Medicine and RadiologyRiachur, Karnataka, India.
[Sen, Subhalakshmi] Manipal University, Manipal College of Dental Sciences, Department of Oral Pathology and Microbiology, 576104 Manipal, Karnataka, India.
[Guddattu, Vasudev] Manipal University, Department of BiostatisticsManipal, Karnataka, India.
[Solomon, Charlotte Monica] Manipal University, Manipal College of Dental Sciences, Department of Oral Pathology and Microbiology, 576104 Manipal, Karnataka, India.
RP Solomon, ChM (reprint author), Manipal University, Manipal College of Dental Sciences, Department of Oral Pathology and Microbiology, 576104 Manipal, India.
EM solomonmc@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1123
EP 1131
DI 10.1007/s12253-015-9940-9
PG 9
ER
PT J
AU Chen, Px
Li, Qy
Yang, Z
AF Chen, Pu-xiang
Li, Qiao-yan
Yang, Zhulin
TI Musashi-1 Expression is a Prognostic Factor in Ovarian Adenocarcinoma and Correlates with ALDH-1 Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; Musashi-1; Immunohistochemistry
ID Ovarian cancer; Musashi-1; Immunohistochemistry
AB The presence of cancer stem-like cells (CSCs) has been demonstrated to be associated with tumor metastasis, chemoresistance, and rapid recurrence of various tumors. The impact of CSC-related markers in the metastasis and prognosis of ovarian cancer has not been well established. In this study, the protein expression of musashi-1 and ALDH1 was measured using immunohistochemistry. Results demonstrated that the percentage of positive musashi-1 and ALDH1 expression were significantly higher in ovarian serous adenocarcinomas, mucinous adenocarcinomas and clear cell adenocarcinomas than in cystadenomas and normal tissues. The percentage of positive musashi-1 and ALDH1 expression were significantly lower in patients identifiedwith clinical stage I or II ovarian adenocarcinomas without lymph node metastasis compared to patients with clinical stage III or IV tumors and lymph node metastasis. The expression of musashi-1 and ALDH1 was found to be highly consistent in ovarian adenocarcinomas. Univariate Kaplan-Meier analysis showed a negative correlation between musashi-1 or ALDH1 expression and overall survival. Multivariate Cox regression analysis showed that positive expression of musashi-1 or ALDH1 in ovarian adenocarcinoma was an independent predictor of poor prognosis. Our study suggested that musashi-1 and ALDH1 expression are closely related to metastasis of ovarian adenocarcinoma. The positive expression of musashi-1 and ALDH1 might be a poor-prognostic factor of ovarian adenocarcinoma.
C1 [Chen, Pu-xiang] Second Xiangya Hospital, Department of Obstetrics and Gynaecology, 410011 Changsha, Hunan, China.
[Li, Qiao-yan] Hunan Provincial People’s Hospital, 410011 Changsha, Hunan, China.
[Yang, Zhulin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
RP Yang, Z (reprint author), Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, China.
EM zhulinyang@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1133
EP 1140
DI 10.1007/s12253-015-9943-6
PG 8
ER
PT J
AU Zhou, L
Yu, L
Ding, G
Chen, W
Zheng, S
Cao, L
AF Zhou, Liangjing
Yu, Leilai
Ding, Guoping
Chen, Wenchao
Zheng, Sixin
Cao, Liping
TI Overexpressions of DLL4 and CD105 are Associated with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DLL4 protein; Endoglin protein; Pancreatic neoplasms; Prognosis
ID DLL4 protein; Endoglin protein; Pancreatic neoplasms; Prognosis
AB The aim of this study was to investigate the expression of Delta-like ligand 4(DLL4) and Endoglin(CD105) labeled microvessel density(MVD) in pancreatic ductal adenocarcinoma (PDAC) and evaluate their correlation with major clinicopathologic features and patients’ survival. Forty-two pancreatic cancer and 20 normal pancreatic tissues were included in the study. Immunohistochemical staining was employed to assess the expression level of DLL4 both in tumor cells and stromal vascular endothelial cells, as well as CD105 which was used to determine MVD. The relationships of DLL4 and CD105 expression with clinicopathologic parameters and clinical outcome were evaluated. Both DLL4 and CD105-labeled microvessel were observed highly immunostained in PDAC cases, and high expression of DLL4 was positively correlated with MVD. Moreover, the high expression of DLL4 was significantly associated with histological grade, node stage and TNM stage in not only the cancer cells but also stroma; while high expression of CD105 was associated with histological grade, TNM stage, node stage and distant metastasis. In univariant analysis, patients with high expression of DLL4 and CD105 tended to significantly poorer overall survival. Both DLL4 and CD105 were overexpressed in a large proportion of patients with PDAC. The expression of DLL4 was positively correlated with CD105-labeled MVD, indicating DLL4 may involved in angiogenesis. In addition, high DLL4 and CD105 expression correlated with the poor clinical outcome and overall survival in patients with PDAC.
C1 [Zhou, Liangjing] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Yu, Leilai] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Ding, Guoping] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Chen, Wenchao] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Zheng, Sixin] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
[Cao, Liping] School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
RP Cao, L (reprint author), School of Medicine, Zhejiang University, Second Affiliated Hospital, Department of Hepatobiliary Surgery, 310006 Hangzhou, China.
EM cao@zju.edu.cn
CR Sarkar FH, Banerjee S, Li Y, 2007, Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol 224(3):326– 336
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Folkman J, 1995, Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1141
EP 1147
DI 10.1007/s12253-015-9937-4
PG 7
ER
PT J
AU Kalmar, A
Peterfia, B
Hollosi, P
Wichmann, B
Bodor, A
Patai, V
Scholler, A
Krenacs, T
Tulassay, Zs
Molnar, B
AF Kalmar, Alexandra
Peterfia, Balint
Hollosi, Peter
Wichmann, Barnabas
Bodor, Andras
Patai, V Arpad
Scholler, Andrea
Krenacs, Tibor
Tulassay, Zsolt
Molnar, Bela
TI Bisulfite-Based DNA Methylation Analysis from Recent and Archived Formalin-Fixed, Paraffin Embedded Colorectal Tissue Samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA methylation; Colorectal cancer; Genomic DNA isolation; Methylation-sensitive high-resolution melting analysis; Pyrosequencing
ID DNA methylation; Colorectal cancer; Genomic DNA isolation; Methylation-sensitive high-resolution melting analysis; Pyrosequencing
AB We aimed to test the applicability of formalin-fixed and paraffin-embedded (FFPE) tissue samples for gene specific DNA methylation analysis after using two commercially available DNA isolation kits. Genomic DNA was isolated from 5 colorectal adenocarcinomas and 5 normal adjacent tissues from "recent", collected within 6 months, and "archived", collected more than 5 years ago, FFPE tissues using either High Pure FFPET DNA Isolation kit or QIAamp DNA FFPE Tissue kit. DNA methylation analysis of MAL, SFRP1 and SFRP2 genes, known to be hypermethylated in CRC, was performed using methylation-sensitive high resolution melting (MS-HRM) analysis and sequencing. QIAamp (Q) method resulted in slightly higher recovery in archived (HP: 1.22± 3.18μg DNA; Q: 3.00±4.04μg DNA) and significantly (p<0.05) higher recovery in recent samples compared to High Pure method (HP) (HP: 4.10±2.91μg DNA; Q: 11.51 ±7.50μg DNA). Both OD260/280 and OD260/230 ratios were lower, but still high in the High Pure isolated archived and recent samples compared to those isolated with QIAamp. Identical DNA methylation patterns were detected for all 3 genes tested by MS-HRM with both isolation kits in the recent group. However, despite of higher DNA recovery in QIAamp slightly more reproducible methylation results were obtained from High Pure isolated archived samples. Sequencing confirmed DNA hypermethylation in CRCs. In conclusion, reproducible DNA methylation patterns were obtained from recent samples using both isolation kits. However, long term storage may affect the reliability of the results leading to moderate differences between the efficiency of isolation kits.
C1 [Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Peterfia, Balint] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Hollosi, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Wichmann, Barnabas] Hungarian Academy of Sciences, Molecular Medicine Research Group, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Bodor, Andras] Eotvos Lorand University, Department of Physics of Complex Systems, Pazmany Peter setany 1/A, 1117 Budapest, Hungary.
[Patai, V Arpad] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Scholler, Andrea] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
RP Kalmar, A (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM alexandra.kalmar@gmail.com
CR Krijgsman O, Israeli D, Haan JC et al, 2012, CGH arrays compared for DNA isolated from formalin-fixed, paraffin-embeddedmaterial. Genes Chromosom Cancer 51(4):344–352., DOI 10.1002/gcc.21920
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TCGA Research Network: http://cancergenome.nih.gov/
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1149
EP 1156
DI 10.1007/s12253-015-9945-4
PG 8
ER
PT J
AU Korkmaz, TD
Demirhan, O
Abat, D
Demirberk, B
Tunc, E
Kuleci, S
AF Korkmaz, Tastemir Deniz
Demirhan, Osman
Abat, Deniz
Demirberk, Bulent
Tunc, Erdal
Kuleci, Sedat
TI Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sex chromosome aneuploidies; Microchimeric cells; Lung cancer; Bladder cancer
ID Sex chromosome aneuploidies; Microchimeric cells; Lung cancer; Bladder cancer
AB The phenomenon of feta-maternal microchimerisms inspires numerous questions. Many questions remain to be answered regarding this new avenue of genetics. The X and Y chromosomes have been associated with malignancy in different types of human tumors.We aimed to investigate the numerical aberrations of chromosomes X and Y in lung cancer (LC) and bladder cancer (BC) and review recent evidence for possible roles of microchimeric cells (McCs) in these cancers. We carried out cytogenetic analysis of the tumor and blood sampling in 52 cases of people with BC and LC, and also with 30 healthy people. A total of 48 (92.3 %) of the patients revealed sex chromosome aneuploidies (SCAs). A total SCAs was found in 9.8 % of 2282 cells that were analyzed as one or more cells in each case. The 68 and 95 SCAs were found in the 1952 (8.4 %) cells in peripheral blood, and 41 and 19 SCAs in the 330 (18.2 %) cells in the tumoral tissues respectively. There was a significant difference in the frequencies of SCAs between the patients and the control groups determined by the Fischer’s Exact Test (p<0.0001). The frequencies of SCAs were higher in the tumoral tissues than in the blood (p<0.0001). There was a significant difference in the frequencies of SCAs between the tumor and blood tissues, and this was higher in the tumor tissue (p<0.0001). In general, 78.9 % (41) of the 52 patients with LC and BC had X and Y chromosome monosomies. Largely a Y chromosome loss was present in 77.8 % of the men, and the 47, XXY karyotype was found in 33.3 % of them. The second most common SCA was monosomy X, and was found in 71.4 % of the women. McCs were observed in 26.9 % of the 52 patients, and the frequencies of McCs were higher in the blood than in the tissues (p<0.0001). XY cells were identified in the lung and bladder tissues of the women who had been pregnant with boys, but not in those who had not. There was a significant difference in the frequencies of McCs between the LC and BC patients (p<0.0005). We speculate that the microchimerism could have a general beneficial role in cancer, in which some sites may not be evident because of an allogeneic maternal immune reaction that hastens cancer development. A further understanding of McCs may help in anticipating its implications in cancer. Our results may suggest that SCAs may be contributing factors in the development of LC and BC, and aneuploidies of X and Y chromosomes play a role in the pathogenesis of cancers.
C1 [Korkmaz, Tastemir Deniz] Adiyaman University, Vocational School of Health Services, AltinsehirAdiyaman, Turkey.
[Demirhan, Osman] Cukurova University, Faculty of Medicine, Department of Medical Biology and Genetics, 01330 Adana, Turkey.
[Abat, Deniz] Cukurova University, Faculty of Medicine, Department of UrologyAdana, Turkey.
[Demirberk, Bulent] Adana Mental and Nervous diseases’ HospitalAdana, Turkey.
[Tunc, Erdal] Cukurova University, Faculty of Medicine, Department of Medical Biology and Genetics, 01330 Adana, Turkey.
[Kuleci, Sedat] Cukurova University, Faculty of Medicine, Department of Chest DiseasesAdana, Turkey.
RP Demirhan, O (reprint author), Cukurova University, Faculty of Medicine, Department of Medical Biology and Genetics, 01330 Adana, Turkey.
EM osdemir@cu.edu.tr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1157
EP 1165
DI 10.1007/s12253-015-9934-7
PG 9
ER
PT J
AU Moizs, M
Bajzik, G
Lelovics, Zs
Strausz, J
Rakvacs, M
Zadori, P
Kovacs,
Repa, I
AF Moizs, Mariann
Bajzik, Gabor
Lelovics, Zsuzsanna
Strausz, Janos
Rakvacs, Marianna
Zadori, Peter
Kovacs, Arpad
Repa, Imre
TI Characterization of Individuals Taking Part in Low Dose Computed Tomography (LDCT) Screening Program
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Lung screening; Participation rate; Hungary
ID Lung cancer; Lung screening; Participation rate; Hungary
AB In the past years the participation rate in conventional voluntary x-ray lung screening has been around 22%in Somogy County in Hungary. Due to the high morbidity and mortality rates of lung cancer, low participation rate of the high risk individuals on the screening is a primary question in Hungary. To obtain an effectively high level of participation in our ongoing low dose CT screening program, we had to emphasize the benefits of participation for the targeted individuals. As a first step, our aim was to gather information on the aspects affecting the individuals’ will for participation.We used the most accessible source of information: individuals over the age of 50, who attended the conventional voluntary lung screening, were approached to fill a questionnaire on their habits relating to smoking, health issues and their prior participation of lung screening. 1080 adults anonymously completed the questionnaire. Analyzing the results, beside other findings, we found a unique variable factor, which altered negatively the compliance for the screening: older individuals, who started participating in the screening in obligation to the health regulations, took part in the voluntary screening programs at a significantly lower rate. Our findings led us to better understanding the complexity of decision making affecting the individual’s participation and attitudes toward health issues. Trial registration: IG/03833/2012.
C1 [Moizs, Mariann] Kaposi Mor Teaching Hospital, Tallian Gyula u. 20-32, H-7400 Kaposvar, Hungary.
[Bajzik, Gabor] Kaposvar University, Department of Radiation Oncology, Guba Sandor u. 40, H-7400 Kaposvar, Hungary.
[Lelovics, Zsuzsanna] Kaposi Mor Teaching Hospital, Tallian Gyula u. 20-32, H-7400 Kaposvar, Hungary.
[Strausz, Janos] Kaposi Mor Teaching Hospital, Tallian Gyula u. 20-32, H-7400 Kaposvar, Hungary.
[Rakvacs, Marianna] Kaposi Mor Teaching Hospital, Tallian Gyula u. 20-32, H-7400 Kaposvar, Hungary.
[Zadori, Peter] Kaposvar University, Department of Radiation Oncology, Guba Sandor u. 40, H-7400 Kaposvar, Hungary.
[Kovacs, Arpad] Kaposvar University, Department of Radiation Oncology, Guba Sandor u. 40, H-7400 Kaposvar, Hungary.
[Repa, Imre] Kaposi Mor Teaching Hospital, Tallian Gyula u. 20-32, H-7400 Kaposvar, Hungary.
RP Repa, I (reprint author), Kaposi Mor Teaching Hospital, H-7400 Kaposvar, Hungary.
EM repa.imre@sic.ke.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1167
EP 1173
DI 10.1007/s12253-015-9929-4
PG 7
ER
PT J
AU Nikkuni, O
Kaira, K
Toyoda, M
Shino, M
Sakakura, K
Takahashi, K
Tominaga, H
Oriuchi, N
Suzuki, M
Iijima, M
Asao, T
Nishiyama, M
Nagamori, Sh
Kanai, Y
Oyama, T
Chikamatsu, K
AF Nikkuni, Osamu
Kaira, Kyoichi
Toyoda, Minoru
Shino, Masato
Sakakura, Koichi
Takahashi, Katsumasa
Tominaga, Hideyuki
Oriuchi, Noboru
Suzuki, Masami
Iijima, Misa
Asao, Takayuki
Nishiyama, Masahiko
Nagamori, Shushi
Kanai, Yoshikatsu
Oyama, Tetsunari
Chikamatsu, Kazuaki
TI Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Larynx; LAT1; CD98; Imunohistochemistry; ASCT2; Prognostic factor
ID Larynx; LAT1; CD98; Imunohistochemistry; ASCT2; Prognostic factor
AB The aim of this study is to evaluate the clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with advanced laryngeal squamous cell carcinoma (LSCC). A total of 73 patients with advanced LSCC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, 4F2hc, system ASC amino acid transporter-2 (ASCT2), cell proliferation by Ki-67, microvessel density (MVD) determined by CD34 and p53. A positive LAT1, 4F2hc and ASCT2 expression (staining more than a quarter) in the primary sites were recognized in 85, 80 and 45 %, respectively, and a high LAT1, 4F2hc and ASCT2 expression (staining more than a half) yielded 48, 31 and 18 %, respectively. High expression of LAT1 was significantly associated with lymph node metastasis, 4F2hc, ASCT2, Ki-67 and p53. The expression of LAT1 was significantly correlated with ASCT2, 4F2hc, cell proliferation, and MVD. By univariate analysis, there was no statistically significant relationship between LAT1 expression and prognosis in advanced LSCC. LAT1, 4F2hc and ASCT2 were highly expressed in patients with advanced laryngeal cancer. Our study suggests that the expression of LAT1 plays a crucial role in the metastasis and tumor progression in advanced LSCC.
C1 [Nikkuni, Osamu] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
[Kaira, Kyoichi] Gunma University, Graduate School of Medicine, Department of Oncology Clinical Development, Showa-machi, 371-8511 Maebashi, Japan.
[Toyoda, Minoru] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
[Shino, Masato] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
[Sakakura, Koichi] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
[Takahashi, Katsumasa] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
[Tominaga, Hideyuki] Fukushima Medical University, Advanced Clinical Research CenterFukushima, Japan.
[Oriuchi, Noboru] Gunma University, Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear medicineMaebashi, Japan.
[Suzuki, Masami] Gunma Prefectural Cancer Center, Department of Head & Neck SurgeryOta, Japan.
[Iijima, Misa] Gunma Prefectural Cancer Center, Department of Pathology and Clinical LaboratoriesOta, Japan.
[Asao, Takayuki] Gunma University, Graduate School of Medicine, Department of Oncology Clinical Development, Showa-machi, 371-8511 Maebashi, Japan.
[Nishiyama, Masahiko] Gunma University, Graduate School of Medicine, Department of Molecular Pharmacology and OncologyMaebashi, Japan.
[Nagamori, Shushi] Osaka University, Graduate School of Medicine, Division of Bio-system PharmacologyOsaka, Japan.
[Kanai, Yoshikatsu] Osaka University, Graduate School of Medicine, Division of Bio-system PharmacologyOsaka, Japan.
[Oyama, Tetsunari] Gunma University, Graduate School of Medicine, Department of Diagnostic PathologyMaebashi, Japan.
[Chikamatsu, Kazuaki] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck SurgeryMaebashi, Japan.
RP Kaira, K (reprint author), Gunma University, Graduate School of Medicine, Department of Oncology Clinical Development, 371-8511 Maebashi, Japan.
EM kkaira1970@yahoo.co.jp
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Kaira K, Oriuchi N, Imai H et al, 2009, Prognostic significance of L-type amino acid transporter 1, LAT1, and 4F2 heavy chain, CD98, expression in stage I pulmonary adenocarcinoma. Lung Cancer 66:120–126
Namikawa M, Kakizaki S, Kaira K, et al, 2014, Expression of amino acid transporters, LAT1, ASCT2 and xCT, as clinical significance in hepatocellular carcinoma. Hepatol Res in press
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1175
EP 1181
DI 10.1007/s12253-015-9954-3
PG 7
ER
PT J
AU Stahl, RP
Schnellert, J
Koop, Ch
Simon, R
Marx, A
Izbicki, RJ
Sauter, G
Quaas, A
AF Stahl, R Phillip
Schnellert, Jessica
Koop, Christina
Simon, Ronald
Marx, Andreas
Izbicki, R Jakob
Sauter, Guido
Quaas, Alexander
TI Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tissue microarrays; Colorectal cancer; Heterogeneity; p53; HER2
ID Tissue microarrays; Colorectal cancer; Heterogeneity; p53; HER2
AB Cancer is often heterogeneous both on a morphological and on a genetic level. Though resected tumors are often large, molecular tumor analysis is usually restricted to one tissue block. In this project we introduce a new tool for a highthroughput heterogeneity analysis of colorectal cancer. A heterogeneity tissuemicroarray (TMA) wasmanufactured fromtissues of 340 patients with colorectal cancer. For this purpose 8 different tissue spots were taken from as many different cancer blocks per patient as possible (at least 4 different blocks). Additional tissue samples from 1 to 4 corresponding lymph node metastases were added from 134 patients. The systemwas then validated by analysing one parameter each known for minimal (p53) or substantial (HER2) heterogeneity in colorectal cancer. P53 alterations as detected by immunohistochemistry were seen in 174 (51.3%) of 339 analyzable primary tumors of which 23 (13.2% of positive cases) showed a heterogeneous distribution pattern. HER2 overexpression was seen in 18 (5.4 %) of 336 evaluable tumors. HER2 amplification occurred in 6 (33.3 %) of the 18 cases with HER2 overexpression. Genomic heterogeneity was more prevalent for HER2 alterations than for p53 alterations. For immunohistochemical expression analysis, 16 of 18 positive cases were heterogeneous (88.9 %) and for amplification 3 of 6 cases (50 %) were heterogeneous. Large section validation revealed, however a considerable fraction of heterogeneous cases were due to technical artifacts. In summary, our data suggest, that heterogeneity TMAs are a powerful tool to rapidly screen for molecular heterogeneity in colorectal cancer.
C1 [Stahl, R Phillip] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Schnellert, Jessica] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Koop, Christina] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Simon, Ronald] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Marx, Andreas] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Izbicki, R Jakob] University Medical Center Hamburg-Eppendorf, General, Visceral and Thoracic Surgery Department, Martinistrasse 52, 20246 Hamburg, Germany.
[Sauter, Guido] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Quaas, Alexander] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
RP Stahl, RP (reprint author), University Medical Center Hamburg Eppendorf, Pathology, 20246 Hamburg, Germany.
EM p.stahl@uke.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1183
EP 1189
DI 10.1007/s12253-015-9953-4
PG 7
ER
PT J
AU San-Miguel, T
Pinto, S
Navarro, L
Callaghan, CR
Monteagudo, C
Lopez-Gines, C
Cerda-Nicolas, M
Gil-Benso, R
AF San-Miguel, Teresa
Pinto, Sandra
Navarro, Lara
Callaghan, C Robert
Monteagudo, Carlos
Lopez-Gines, Concha
Cerda-Nicolas, Miguel
Gil-Benso, Rosario
TI Expression of the Chemokine Receptors CXCR3, CXCR4, CXCR7 and Their Ligands in Rhabdomyosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Alveolar Rhabdomyosarcoma; Chemokines; Embryonal Rhabdomyosarcoma; Flow cytometry
ID Alveolar Rhabdomyosarcoma; Chemokines; Embryonal Rhabdomyosarcoma; Flow cytometry
AB Rhabdomyosarcomas (RMS) are soft tissue malignant tumors of childhood and adolescents. The mechanisms underlying their aggressiveness are still poorly understood. Chemokines are chemotactic proteins involved in pathological processes that have been intensely studied in several types of cancers because of their influence in migration, angiogenesis, or metastases.We analyzed the expression of the chemokine receptors CXCR3, CXCR4 and CXCR7 and their ligands CXCL9, CXCL10, CXCL11 and CXCL12, in 15 RMS samples derived from nine patients. Expression was measured in tumors and primary cultures of RMS by Real-Time Polymerase Chain Reaction, immunostaining and flow cytometry. Our results show that these receptors are widely expressed in RMS. A significant difference between CXCL12/CXCR4, CXCL12/CXCR7, CXCL11/CXCR7 expression ratios was found in alveolar versus embryonal RMS and similarly between CXCL12/CXCR4 and CXCL11/CXCR3 ratios in primary versus recurrent tumors. These findings suggest a possible association between the interrelation of chemokine/ chemokine-receptor and an aggressive biological behavior in RMS.
C1 [San-Miguel, Teresa] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Pinto, Sandra] University of Coimbra, Center for Neuroscience and Cell Biology – CNC.IBILI, Blasco Ibanez,17, 3004-517 Coimbra, Portugal.
[Navarro, Lara] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Callaghan, C Robert] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Monteagudo, Carlos] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Lopez-Gines, Concha] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Cerda-Nicolas, Miguel] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
[Gil-Benso, Rosario] University of Valencia, Department of Pathology, Blasco Ibanez, 15, 46010 Valencia, Spain.
RP San-Miguel, T (reprint author), University of Valencia, Department of Pathology, 46010 Valencia, Spain.
EM teconsan@uv.es
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1191
EP 1199
DI 10.1007/s12253-015-9947-2
PG 9
ER
PT J
AU Chen, YT
Tsao, ShCh
Yuan, FShSh
Tsai, HP
Chai, ChY
AF Chen, Yi-Ting
Tsao, Shu-Chuan
Yuan, F Shyng-Shiou
Tsai, Hung-Pei
Chai, Chee-Yin
TI Serine Protease Inhibitor Kazal Type 1 (SPINK1) Promotes Proliferation of Colorectal Cancer Through the Epidermal Growth Factor as a Prognostic Marker
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Epidermal growth factor receptor (EGFR); Serine protease inhibitor Kazal type-1 (SPINK1); Tumor-associated trypsin inhibitor (TATI)
ID Colorectal cancer; Epidermal growth factor receptor (EGFR); Serine protease inhibitor Kazal type-1 (SPINK1); Tumor-associated trypsin inhibitor (TATI)
AB Serine protease inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is involved in inflammation, cell proliferation and carcinogenesis. The role and association between SPINK1, EGFR and Ki-67 in colorectal adenoma (CRA) and colorectal cancer (CRC) are still unknown. In this study, we used immunohistochemical stain to evaluate expression of SPINK1, EGFR and Ki-67 proteins in 30 CRA and 53 CRC patients semiquantitatively, and then analyzed their correlation with clinicopathologic parameters. Our results revealed that SPINK1 expression was noted in the upper and basal parts of the crypts in CRA and was more intensely related with cellular atypia. EGFR expression was found in 13 out of 30 adenomas, including 9 out of 15 adenomas with dysplasia or synchronous CRC (60 %), and 4 out of 15 adenomas without dysplasia (26.7 %). In CRC, high SPINK1 expression was significantly associated with males (p= 0.041) and advanced disease stage (p=0.015). EGFR positivity was significantly correlated with higher T stage (p=0.004) and disease stage (stage I-IV, p=0.017; early vs. late, p=0.015). Pearson’s correlation showed positive correlation between the SPINK1 intensity and EGFR immunoreactivity (p=0.011), and Ki-67 and SPINK1 intensity or percentage (p=0.017 and p=0.039 respectively). In Kaplan-Meier analyses, patients with high SPINK1 intensity tended to have shorter overall survival (p=0.03). Concomitant expression of high SPINK1 intensity and EGFR was also identified as being associated with poor prognosis (p=0.015). In conclusion, high SPINK1 expression is associated with advanced stage and poor prognosis. There is positive correlation between high SPINK1 expression, EGFR immunoreactivity, and high Ki- 67 labeling index. The SPINK1 protein seems to play a role in tumor proliferation and malignant transformation through the EGFR pathway. SPINK1 may serve as a prognostic biomarker in therapeutic targeting in the future.
C1 [Chen, Yi-Ting] Kaohsiung Medical University, College of Medicine, Department of Pathology, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Tsao, Shu-Chuan] Kaohsiung Medical University, College of Medicine, Department of Pathology, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Yuan, F Shyng-Shiou] Kaohsiung Medical University, Cancer Center, Department of Medical Research, Translational Research CenterKaohsiung, Taiwan, Republic of China.
[Tsai, Hung-Pei] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Chai, Chee-Yin] Kaohsiung Medical University, College of Medicine, Department of Pathology, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
RP Chai, ChY (reprint author), Kaohsiung Medical University, College of Medicine, Department of Pathology, 807 Kaohsiung, Taiwan, Republic of China.
EM cychai@kmu.edu.tw
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1201
EP 1208
DI 10.1007/s12253-015-9949-0
PG 8
ER
PT J
AU Ipekci, T
Ozden, F
Unal, B
Saygin, C
Uzunaslan, D
Ates, E
AF Ipekci, Tumay
Ozden, Ferhat
Unal, Betul
Saygin, Caner
Uzunaslan, Didem
Ates, Erhan
TI Epithelial-Mesenchymal Transition Markers β-catenin, Snail, and E-Cadherin do not Predict Disease Free Survival in Prostate Adenocarcinoma: a Prospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Epithelial-mesenchymal transition; β-catenin; Snail; E-cadherin; Survival
ID Prostate cancer; Epithelial-mesenchymal transition; β-catenin; Snail; E-cadherin; Survival
AB Current methods for diagnosis and staging of prostate adenocarcinoma are not sensitive enough to distinguish between patients with indolent disease and those that should receive radical treatment. Epithelial-mesencyhmal transition (EMT) is a well-characterized process involved in tumor invasion and metastasis. The aim of this study is to analyze the expression of β-catenin, Snail, and E-cadherin in prostate cancer patients with prospective evaluation of their value in predicting disease-free survival (DFS). One-hundred-andthree consecutive prostate carcinoma patients who underwent radical prostatectomy and 35 patients with benign prostate hyperplasia (BPH) were enrolled. Age, initial PSA level, tumor size and clinical stage were documented for adenocarcinoma patients and they were enrolled in active surveillance with serum PSA levels. Recurrence was defined as PSA level of ≥0.2 ng/ml on at least 2 occasions over a 2-month period. Immunohistochemical staining intensity was scored as negative, weakly positive, moderately positive, and strongly positive. For Snail and β-catenin immunoreaction, the tumors were considered nuclear positive when more than 5 % of the nuclei of tumor cells were positively stained. Patients with prostate cancer had weaker β-catenin (p<0.0001), Snail (p= 0.006), and E-cadherin (p=0.02) staining when compared to BPH patients and the frequency of nuclear positivity for β- catenin and Snail were higher in adenocarcinoma group (p< 0.0001). Increased expression and nuclear positivity of β- catenin were associated with advanced stage (p=0.012 and p=0.003) and higher tumor volume (p=0.013 and p=0.002). Additionally, patients with increased Snail expression had higher Gleason scores and tumor volume at presentation (p= 0.008 and p=0.004). However, there were no significant DFS differences in adenocarcinoma patients who did and did not have β-catenin, Snail, and E-cadherin expression as assessed with log-rank test. Expressions of β-catenin, Snail, and Ecadherin were significantly lower in prostate cancer patients compared to BPH patients and both β-catenin and Snail had nuclear staining pattern in patients with adenocarcinoma. However, none of these markers predicted DFS in 36-month follow up of our cohort.
C1 [Ipekci, Tumay] Antalya Training and Research Hospital, Department of UrologyAntalya, Turkey.
[Ozden, Ferhat] Van Regional Training and Research Hospital, Department of PathologyVan, Turkey.
[Unal, Betul] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Saygin, Caner] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Kocamustafapasa, Fatih, 0340090 Istanbul, Turkey.
[Uzunaslan, Didem] Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, Kocamustafapasa, Fatih, 0340090 Istanbul, Turkey.
[Ates, Erhan] Antalya Training and Research Hospital, Department of UrologyAntalya, Turkey.
RP Saygin, C (reprint author), Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine, 0340090 Istanbul, Turkey.
EM csaygin@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1209
EP 1216
DI 10.1007/s12253-015-9958-z
PG 8
ER
PT J
AU Bittner, N
Baliko, Z
Sarosi, V
Laszlo, T
Toth, E
Kasler, M
Geczi, L
AF Bittner, Nora
Baliko, Zoltan
Sarosi, Veronika
Laszlo, Terezia
Toth, Erika
Kasler, Miklos
Geczi, Lajos
TI Bone Metastases and the EGFR and KRAS Mutation Status in Lung Adenocarcinoma - The Results of Three Year Retrospective Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; Skeletal related events; Tyrosine kinase inhibitors; EGFR mutation; KRAS mutation
ID Lung adenocarcinoma; Skeletal related events; Tyrosine kinase inhibitors; EGFR mutation; KRAS mutation
AB Lung cancer is a heterogeneous group of disease and mutational profiling of lung adenocarcinomas is a routine practice in thoracic oncology. Kirsten-RAS (KRAS) and EGFR mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas. Our aim was to investigate the correlation between bone metastases and EGFR and KRAS mutation status in lung adenocarcinoma patients. Retrospectively we analysed 224 patients with recurrent or metastatic lung adenocarcinomas. Patients were treated with standard chemotherapy as first line therapy and with EGFRTK inhibitors as a second or third line therapy. 72 of 224 patients (32 %) had verified bone metastases. Bone metastases and Skeletal Related Events (SRE) were more frequent in men, heavy smokers and without treatment of EGFR TK inhibitors. We have found that EGFR and KRAS mutation status are both predictive factors for the treatment efficacy and prognostic factors for the disease progression. However there were no significant correlation between mutation status and the presence of bone metastases (P=0, 59). In our study the presence of bone metastases proved to be an independent prognostic factor related to poor performance status and worse Quality of Life (QL).
C1 [Bittner, Nora] National Institute of OncologyBudapest, Hungary.
[Baliko, Zoltan] University of Pecs, Faculty of Medicine, Department of PulmonologyPecs, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of Medicine, Department of PulmonologyPecs, Hungary.
[Laszlo, Terezia] University of Pecs, Faculty of Medicine, Department of PulmonologyPecs, Hungary.
[Toth, Erika] National Institute of OncologyBudapest, Hungary.
[Kasler, Miklos] National Institute of OncologyBudapest, Hungary.
[Geczi, Lajos] National Institute of OncologyBudapest, Hungary.
RP Bittner, N (reprint author), National Institute of Oncology, Budapest, Hungary.
EM nora_bittner@yahoo.ca
CR Jemal A, Siegel R, Ward E, Hao Y, 2009, Cancer statistic, 2009. CA Cancer J Clin 59:225–249
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1217
EP 1221
DI 10.1007/s12253-015-9955-2
PG 5
ER
PT J
AU Pala, EE
Bayol, U
Keskin, UE
Ozguzer, A
Kucuk, U
Ozer, O
Koc, A
AF Pala, Ebru Emel
Bayol, Umit
Keskin, Usturali Elif
Ozguzer, Alp
Kucuk, Ulku
Ozer, Ozge
Koc, Altug
TI Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Triple negative breast cancer; EGFR; p53; HER2
ID Triple negative breast cancer; EGFR; p53; HER2
AB Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18–23), p53 (exon 5–8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening.We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.
C1 [Pala, Ebru Emel] Tepecik Education and Research Hospital, Pathology Department, Gaziler Caddesi, Yenisehir, 35000 Izmir, Turkey.
[Bayol, Umit] Tepecik Education and Research Hospital, Pathology Department, Gaziler Caddesi, Yenisehir, 35000 Izmir, Turkey.
[Keskin, Usturali Elif] Tepecik Education and Research Hospital, Pathology Department, Gaziler Caddesi, Yenisehir, 35000 Izmir, Turkey.
[Ozguzer, Alp] Tepecik Education and Research Hospital, Pathology Department, Gaziler Caddesi, Yenisehir, 35000 Izmir, Turkey.
[Kucuk, Ulku] Tepecik Education and Research Hospital, Pathology Department, Gaziler Caddesi, Yenisehir, 35000 Izmir, Turkey.
[Ozer, Ozge] Genetic DepartmentIzmir, Turkey.
[Koc, Altug] Genetic DepartmentIzmir, Turkey.
RP Pala, EE (reprint author), Tepecik Education and Research Hospital, Pathology Department, 35000 Izmir, Turkey.
EM emelozkok@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1223
EP 1227
DI 10.1007/s12253-015-9956-1
PG 5
ER
PT J
AU Winczura, P
Sosinska-Mielcarek, K
Duchnowska, R
Badzio, A
Lakomy, J
Majewska, H
Peksa, R
Pieczynska, B
Radecka, B
Debska-Szmich, S
Adamowicz, K
Biernat, W
Jassem, J
AF Winczura, Piotr
Sosinska-Mielcarek, Katarzyna
Duchnowska, Renata
Badzio, Andrzej
Lakomy, Joanna
Majewska, Hanna
Peksa, Rafal
Pieczynska, Beata
Radecka, Barbara
Debska-Szmich, Sylwia
Adamowicz, Krzysztof
Biernat, Wojciech
Jassem, Jacek
TI Immunohistochemical Predictors of Bone Metastases in Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Bone metastases; Predictive factors; Immunohistochemistry
ID Breast cancer; Bone metastases; Predictive factors; Immunohistochemistry
AB Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate imumohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p=0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p=0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p=0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p<0.0001, respectively; HR 1.79, p=0.013). Luminal A (43 vs. 23 % respectively, p=0.009) and luminal B/HER2-positive (16 vs. 4.9 % respectively, p=0.032) subtypes were more common in patients with- compared to those without BM, whereas triple negative breast cancer subtype was less common (16 vs. 38 %, p=0.002).
C1 [Winczura, Piotr] Medical University of GdanskGdansk, Poland.
[Sosinska-Mielcarek, Katarzyna] Medical University of Gdansk, Department of Oncology and RadiotherapyGdansk, Poland.
[Duchnowska, Renata] Military Institute of MedicineWarsaw, Poland.
[Badzio, Andrzej] Medical University of GdanskGdansk, Poland.
[Lakomy, Joanna] Medical University of GdanskGdansk, Poland.
[Majewska, Hanna] Medical University of GdanskGdansk, Poland.
[Peksa, Rafal] Medical University of GdanskGdansk, Poland.
[Pieczynska, Beata] Medical University of GdanskGdansk, Poland.
[Radecka, Barbara] Regional Oncology CenterOpole, Poland.
[Debska-Szmich, Sylwia] Medical University of LodzLodz, Poland.
[Adamowicz, Krzysztof] Medical University of Gdansk, Department of Oncology and RadiotherapyGdansk, Poland.
[Biernat, Wojciech] Medical University of GdanskGdansk, Poland.
[Jassem, Jacek] Medical University of GdanskGdansk, Poland.
RP Winczura, P (reprint author), Medical University of Gdansk, Gdansk, Poland.
EM pwinczura@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1229
EP 1236
DI 10.1007/s12253-015-9957-0
PG 8
ER
PT J
AU Singh, KM
Singh, L
Pushker, N
Sen, S
Sharma, A
Chauhan, AF
Kashyap, S
AF Singh, Kumar Mithalesh
Singh, Lata
Pushker, Neelam
Sen, Seema
Sharma, Anjana
Chauhan, Ahamad Feeroj
Kashyap, Seema
TI Correlation of High Mobility Group Box-1 Protein (HMGB1) with Clinicopathological Parameters in Primary Retinoblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Retinoblastoma; Immunohistochemistry; HMGB1; RT-PCR
ID Retinoblastoma; Immunohistochemistry; HMGB1; RT-PCR
AB HMGB1 is considered to be DNA chaperone as it binds without any specificity. It is the structural protein which alters nuclear homeostasis and genomic stability of chromatin. Its role in retinoblastoma (Rb) remains unclear. The aim of the present study was to evaluate the expression of HMGB1 protein in primary enucleated retinoblastomas. Expression of HMGB1 in 69 prospective cases of primary retinoblastoma were assessed by immunohistochemistry and reverse transcriptase PCR (RT-PCR) technique and correlated with clinicopathological parameters. Immunohistochemical staining revealed expression of HMGB1 in 55.07%(38/69) cases. Semiquantitative RT-PCR was performed on 31 fresh tumor tissues. mRNA expression was observed in 77.41 % (24/31) cases. Expression of HMGB1 was statistically significant with poor tumor differentiation (p=0.0440) & optic nerve invasion (p=0.0128).HMGB1 expression was frequently seen in poorly differentiated tumors and those with histopathological high risk factors. Therefore, HMGB1 may contribute to tumor invasiveness and could serve as a poor prognostic marker in Rb.
C1 [Singh, Kumar Mithalesh] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Singh, Lata] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Pushker, Neelam] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of OphthalmologyNew Delhi, India.
[Sen, Seema] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Sharma, Anjana] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular MicrobiologyNew Delhi, India.
[Chauhan, Ahamad Feeroj] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Kashyap, Seema] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
RP Kashyap, S (reprint author), All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular Pathology, New Delhi, India.
EM dr_skashyap@hotmail.com
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Liu F, Zhang Y, Peng Z, Gao H, Xu L, Chen M, 2012, High expression of high mobility group box 1, hmgb1, predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy. J Transl Med 10:135–144
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1237
EP 1242
DI 10.1007/s12253-015-9951-6
PG 6
ER
PT J
AU Avci, N
Ture, M
Deligonul, A
Cubukcu, E
Olmez, FO
Sahinturk, S
Topak, A
Kurt, E
Evrensel, T
Sahin, BA
Yakut, T
AF Avci, Nilufer
Ture, Mehmet
Deligonul, Adem
Cubukcu, Erdem
Olmez, Fatih Omer
Sahinturk, Serdar
Topak, Ali
Kurt, Ender
Evrensel, Turkkan
Sahin, Bilgehan Ahmet
Yakut, Tahsin
TI Association and Prognostic Significance of the Functional −1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Matrix metalloproteinases; Polymorphism; Association study; Prognosis
ID Gastric cancer; Matrix metalloproteinases; Polymorphism; Association study; Prognosis
AB Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case–control design the association between the functional −1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case–control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 −1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR=0.89, 95 % confidence interval [CI]=0.44–1.82, P=0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR=0.81, 95 % CI=0.40–1.94, P=0.84). When the MMP-9 −1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjectswith the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9−1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.
C1 [Avci, Nilufer] Ali Osman Sonmez Oncology Hospital, Department of Medical OncologyBursa, Turkey.
[Ture, Mehmet] Uludag University Medicine Faculty, Department of Medical GeneticsBursa, Turkey.
[Deligonul, Adem] Uludag University Medicine Faculty, Department of Medical OncologyBursa, Turkey.
[Cubukcu, Erdem] Ali Osman Sonmez Oncology Hospital, Department of Medical OncologyBursa, Turkey.
[Olmez, Fatih Omer] Medipol University School of Medicine, Department of Medical OncologyIstanbul, Turkey.
[Sahinturk, Serdar] Uludag University Medicine Faculty, Department of Medical GeneticsBursa, Turkey.
[Topak, Ali] Uludag University Medicine Faculty, Department of Medical GeneticsBursa, Turkey.
[Kurt, Ender] Uludag University Medicine Faculty, Department of Medical OncologyBursa, Turkey.
[Evrensel, Turkkan] Uludag University Medicine Faculty, Department of Medical OncologyBursa, Turkey.
[Sahin, Bilgehan Ahmet] Uludag University Medicine Faculty, Department of Internal MedicineBursa, Turkey.
[Yakut, Tahsin] Uludag University Medicine Faculty, Department of Medical GeneticsBursa, Turkey.
RP Avci, N (reprint author), Ali Osman Sonmez Oncology Hospital, Department of Medical Oncology, Bursa, Turkey.
EM drniluferavci@hotmail.com
CR Fock KM, 2014, Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther 40:250–260
de Martel C, Forman D, Plummer M, 2013, Gastric cancer: epidemiology and risk factors. Gastroenterol Clin N Am 42:219–240
Lordick F, Allum W, Carneiro F, Mitry E, Tabernero J, Tan P, Van Cutsem E, van de Velde C, Cervantes A, 2014, Unmet needs and challenges in gastric cancer: the way forward. Cancer Treat Rev 40: 692–700
CrewKD, Neugut AI, 2006, Epidemiology of gastric cancer.World J Gastroenterol 12:354–362
Shi J, Qu YP, Hou P, 2014, Pathogenetic mechanisms in gastric cancer. World J Gastroenterol 20:13804–13819
McLean MH, El-Omar EM, 2014, Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 11:664–674
Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R, Kaur G, 2014, Matrix metalloproteinases and cancer—roles in threat and therapy. Asian Pac J Cancer Prev 15:1085–1091
Nissinen L, Kahari VM, 2014, Matrix metalloproteinases in inflammation. Biochim Biophys Acta 1840:2571–2580
Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S, 2014, Matrix metalloproteinases and gastrointestinal cancers: impacts of dietary antioxidants. World J Biol Chem 5:355–376
Sampieri CL, Leon-Cordoba K, Remes-Troche JM, 2013, Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers. J Cancer Res Ther 9:356–363
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ZhangQW, Liu L, Chen R,Wei YQ, Li P, Shi HS, ZhaoYW(2012, Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis. Asian Pac J Cancer Prev 13:2903–2908
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Gong LL, Liu H, Liu LH, 2014, Lack of association between matrix metalloproteinase-9 gene-1562C/T polymorphism and preeclampsia: a meta-analysis. Hypertens Pregnancy 33:389–394
Yang TF, Guo L, Wang Q, 2014, Meta-analysis of associations between four polymorphisms in the matrix metalloproteinases gene and gastric cancer risk. Asian Pac J Cancer Prev 15:1263–1267
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Wang L, Ma YT, Xie X, Yang YN, Fu ZY, Liu F, Li XM, Chen BD, 2011, Association ofMMP-9 gene polymorphisms with acute coronary syndrome in the Uygur population of China. World J Emerg Med 2:104–110
Emanuele E, Lista S, Ghidoni R, Binetti G, Cereda C, Benussi L, Maletta R, Bruni AC, Politi P, 2011, Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer’s disease. Neurobiol Aging 32:1231–1235
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Schveigert D, Valuckas KP, Kovalcis V, Ulys A, Chvatovic G, Didziapetriene J, 2013, Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer. Tumori 99:523–529
Chiranjeevi P, Spurthi KM, Rani NS, Kumar GR, Aiyengar TM, Saraswati M, Srilatha G, Kumar GK, Sinha S, Kumari CS, Reddy BN,Vishnupriya S, Rani HS, 2014, Gelatinase B, −1562C/T, polymorphism in tumor progression and invasion of breast cancer. Tumour Biol 35:1351–1356
El Samanoudy A, Monir R, Badawy A, Ibrahim L, Farag K, El Baz S, Alenizi D, Alenezy A, 2014, Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses. Genet Mol Res 13:8025–8034
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1243
EP 1247
DI 10.1007/s12253-015-9950-7
PG 5
ER
PT J
AU Mallick, S
Breta, M
Gupta, DS
Dinda, KA
Mohanty, KB
Singh, KM
AF Mallick, Saumyaranjan
Breta, Monika
Gupta, Datta Siddhartha
Dinda, Kumar Amit
Mohanty, K Biddhu
Singh, K Manoj
TI Angiogenesis, Proliferative Activity and DNA Ploidy in Oral Verrucous Carcinoma: A Comparative Study Including Verrucous Hyperplasia and Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiogenesis; Proliferative activity; Ploidy; Verrucous carcinoma
ID Angiogenesis; Proliferative activity; Ploidy; Verrucous carcinoma
AB Verrucous carcinoma (VC) is a rare and distinct clinicopathologic variant of well-differentiated squamous cell carcinoma (SCC). This study aims to evaluate the histomorphology, proliferative activity, level of angiogenesis, and DNA ploidy of these pathological entities. This was a retrospective-prospective study of 18 cases of verrucous hyperplasia (VH), 41 cases of VC, and 44 cases of SCC. Immunohistochemical analysis for Ki-67 (MIB-1) and CD34 were performed. The tumor proliferative index, endothelial proliferative index and microvascular density were calculated. DNA ploidy was determined using image cytometry. The age range and gender ratio were similar in all three groups. The differences in MIB-1 labeling index (p=0.0001), microvascular density (p=0.01), and endothelial proliferative index (p= 0.001) between VC and SCC were found to be statistically significant. A non-significant increasing trend was observed in all of these parameters between VH and VC. On ploidy analysis, 100 % of SCC cases were aneuploid, compared to 39 % of VH and 86 % of VC cases. Our study demonstrates a significant difference in tumor proliferation, microvessel density, and ploidy between VC and SCC while increasing trend between VH and VC. These parameters, along with morphological findings, may be useful in differentiating these entities in small mucosal biopsies.
C1 [Mallick, Saumyaranjan] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Breta, Monika] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Gupta, Datta Siddhartha] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Dinda, Kumar Amit] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Mohanty, K Biddhu] All India Institute of Medical Sciences, Department of Radiation oncology, 110029 New Delhi, India.
[Singh, K Manoj] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Singh, KM (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM makusi@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1249
EP 1257
DI 10.1007/s12253-014-9856-9
PG 9
ER
PT J
AU Zhu, L
Liu, J
Shenglin, M
Zhang, Sh
AF Zhu, Lucheng
Liu, Jihong
Shenglin, Ma
Zhang, Shirong
TI Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MALAT-1; LncRNA; Metastasis; Prognosis; Survival; Meta-analysis
ID MALAT-1; LncRNA; Metastasis; Prognosis; Survival; Meta-analysis
AB Elevated expression of MALAT-1 was found in various cancers, and correlated with metastasis and prognostic. This meta-analysis collected all relevant articles and explored correlation of MALAT-1 with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS). A quantitative meta-analysis was performed through a systematic search in PubMed,Web of Science, Medline, CNKI, CBM, and the Cochrane Library. The odds ratios (OR) of LNM and DM and hazard ratio (HR) of OS were calculated to assess the association strength. Eight studies with a total of 845 patients were included in the meta-analysis. Six different types of cancer were evaluated, with 2 non-small cell lung cancer (NSCLC), 1 colorectal cancer (CRC), 1 gastric cancer (GC), 2 pancreatic cancer (PC), 1 clear cell renal cell carcinoma (ccRCC), and 1 osteosarcoma (OSA). Compared with low MALAT-1 expression, high MALAT-1 expression correlated with more LNM (OR=2.08, 95 %CI: 1.00-4.32, p=0.05) by a random-effects model (I2=71 %, p=0.004). A similar result was seen between MALAT-1 expression and DM, the OR was 3.52 (95 %CI: 1.06–11.71, p=0.04) adopting a randomeffects model (I2=59 %, p=0.04). Additionally, our analysis showed a poorer OS in patients with high MALAT-1 expression than those with low MALAT-1 expression (HR=2.12, 95 %CI: 1.60–2.82, p<0.001) adopting a random-effects model (I2=56 %, p=0.04). MALAT-1 may serve as a molecular marker for cancer metastasis and prognosis.
C1 [Zhu, Lucheng] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, huansha Road, shangcheng District, 310006 Hangzhou, China.
[Liu, Jihong] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, huansha Road, shangcheng District, 310006 Hangzhou, China.
[Shenglin, Ma] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, huansha Road, shangcheng District, 310006 Hangzhou, China.
[Zhang, Shirong] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, huansha Road, shangcheng District, 310006 Hangzhou, China.
RP Shenglin, M (reprint author), Hangzhou First People’s Hospital, Department of Medical Oncology, 310006 Hangzhou, China.
EM mashenglin@outlook.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1259
EP 1264
DI 10.1007/s12253-015-9960-5
PG 6
ER
PT J
AU Fabian, M
Toth, V
Somlai, B
Harsing, J
Kuroli, E
Rencz, F
Kuzmanovszki, D
Szakonyi, J
Toth, B
Karpati, S
AF Fabian, Melinda
Toth, Veronika
Somlai, Beata
Harsing, Judit
Kuroli, Eniko
Rencz, Fanni
Kuzmanovszki, Daniella
Szakonyi, Jozsef
Toth, Bela
Karpati, Sarolta
TI Retrospective Analysis of Clinicopathological Characteristics of Pregnancy Associated Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Pregnancy; Postpartum; Young women
ID Melanoma; Pregnancy; Postpartum; Young women
AB Pregnancy associated melanoma (PAM) by definition appears during pregnancy or within 1 year after delivery. In this retrospective study we analysed the pathological characteristics and survival rate of PAM and matched the data with non-pregnant age- and stage-matched control patients. Between 2003 and 2014, 34 pregnant women (aged 32.5±5.6 years) were diagnosed with melanoma at the Department of Dermatology, Venereology and Dermatooncology of the Semmelweis University. During the pathological process histologic subtype, Breslow thickness and Clark level, tumor cell type, mitotic rate, peritumoral inflammation, as well as ulceration, regression, necrosis, vascular invasion and presence of satellitewere analyzed and related to clinical data. Primary tumor location and clinical staging, disease course, local recurrence and metastases, 5-year survival rate, other tumor development before or after the diagnosis of melanoma have also been documented. We found no difference in all parameters between pregnant and non-pregnant melanoma cases except peritumoral inflammation which was higher in PAM group, moreover the presence of mild inflammation was significantly higher in PAM group compared to non-pregnancy associated melanoma (NPAM) women group.
C1 [Fabian, Melinda] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Toth, Veronika] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Somlai, Beata] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Harsing, Judit] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Kuroli, Eniko] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Rencz, Fanni] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Kuzmanovszki, Daniella] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Szakonyi, Jozsef] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Toth, Bela] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Maria street 41, 1085 Budapest, Hungary.
RP Karpati, S (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, 1085 Budapest, Hungary.
EM karpatsar@gmail.com
CR Tomao F, Papa A, Lo Russo G, Zuber S, Spinelli GP, Rossi L, Caruso D, Prinzi N, Stati V, Benedetti Panici P, Tomao S, 2014, Correlation between fertility drugs use and malignant melanoma incidence: the state of the art. Tumour Biol 35(9):8415–8424
Driscoll MS, Grant-Kels JM, 2007, Hormones, nevi, and melanoma: an approach to the patient. J Am Acad Dermatol 57(6):919– 931, quiz 932–6
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Toth V, Somlai B, Harsing J, Hatvani Z, Karpati S, 2013, Stage distribution of malignant melanomas in a Hungarian centre. Orv Hetil 154(25):969–976
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1265
EP 1271
DI 10.1007/s12253-015-9961-4
PG 7
ER
PT J
AU Dong, F
Liu, F
Yan, S
Liu, X
Jiang, Z
Liu, J
AF Dong, Fengyun
Liu, Fuhong
Yan, Suhua
Liu, Xiaochun
Jiang, Zhongmin
Liu, Ju
TI Elevated Expression of CD109 in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Dong, Fengyun] Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, 250014 Jinan, Shandong, China.
[Liu, Fuhong] Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, 250014 Jinan, Shandong, China.
[Yan, Suhua] Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, 250014 Jinan, Shandong, China.
[Liu, Xiaochun] The University of Texas, MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, 1515 Holcombe Blvd, 77030 Houston, TX, USA.
[Jiang, Zhongmin] Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, 250014 Jinan, Shandong, China.
[Liu, Ju] Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, 250014 Jinan, Shandong, China.
RP Jiang, Z (reprint author), Qianfoshan Hospital Affiliated to Shandong University, 250014 Jinan, China.
EM qyjzm@sina.com.cn
CR Stoner GD, Wang LS, Chen T, 2007, Chemoprevention of esophageal squamous cell carcinoma. Toxicol Appl Pharmacol 224(3):337– 349., DOI 10.1016/j.taap.2007.01.030
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Megumi K, Ishigami S, UchikadoY, Kita Y, Okumura H,Matsumoto M, Uenosono Y, Arigami T, Kijima Y, Kitazono M, Shinchi H, Ueno S, Natsugoe S, 2012, Clinicopathological significance of BMP7 expression in esophageal squamous cell carcinoma. Ann Surg Oncol 19(6):2066–2071., DOI 10.1245/s10434-011-2024-5
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Hashimoto M, Ichihara M, Watanabe T, Kawai K, Koshikawa K, Yuasa N, Takahashi T, Yatabe Y, Murakumo Y, Zhang JM, Nimura Y, Takahashi M, 2004, Expression of CD109 in human cancer. Oncogene 23(20):3716–3720., DOI 10.1038/sj.onc.1207418
Ozbay PO, Ekinci T, Yigit S, Yavuzcan A, Uysal S, Soylu F, Cakalagaoglu F, 2013, Investigation of prognostic significance of CD109 expression in women with vulvar squamous cell carcinoma. Onco Targets Ther 6:621–627., DOI 10.2147/OTT.S41069
Zhang JM, Hashimoto M, Kawai K, Murakumo Y, Sato T, Ichihara M, Nakamura S, Takahashi M, 2005, CD109 expression in squamous cell carcinoma of the uterine cervix. Pathol Int 55(4):165– 169., DOI 10.1111/j.1440-1827.2005.01807.x
Duff B, Weigel JA, Bourne P, Weigel PH, McGary CT, 2002, Endothelium in hepatic cavernous hemangiomas does not express the hyaluronan receptor for endocytosis. Hum Pathol 33(3):265–269
Cuppini L, Calleri A, BruzzoneMG, Prodi E, Anghileri E, Pellegatta S, Mancuso P, Porrati P, Di Stefano AL, Ceroni M, Bertolini F, Finocchiaro G, Eoli M, 2013, Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan. PLoS One 8(9):e74345., DOI 10.1371/ journal.pone.0074345
Hagiwara S, Murakumo Y, Sato T, Shigetomi T,Mitsudo K, Tohnai I, UedaM, Takahashi M, 2008, Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity. Cancer Sci 99(10):1916–1923., DOI 10.1111/j.1349-7006. 2008.00949.x
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1273
EP 1275
DI 10.1007/s12253-014-9894-3
PG 3
ER
PT J
AU Kim, JCh
Shin, WJ
Jung, WS
Park, RB
Park, HN
AF Kim, Jae Chang
Shin, Woo Jung
Jung, Won Seok
Park, Ryung Bo
Park, Hwa Neung
TI Somatic Mutation of ARHI Gene in Hepatocellular Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kim, Jae Chang] University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
[Shin, Woo Jung] University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
[Jung, Won Seok] University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
[Park, Ryung Bo] University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
[Park, Hwa Neung] University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
RP Park, HN (reprint author), University of Ulsan, College of Medicine, Ulsan University Hospital, Biomedical Research Center, 682-714 Ulsan, South Korea.
EM airhiro@naver.com
CR Ahn J, Flamm SL, 2004, Hepatocellular carcinoma. Dis Mon 50: 556–573
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Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, KuoWL, Gray JW, Siciliano M, Mills GB, Bast RC Jr, 1999, NOEY2, ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. Proc Natl Acad Sci U S A 96:214–219
Luo RZ, Fang X, Marquez R, Liu SY,Mills GB, LiaoWS,Yu Y, Bast RC, 2003, ARHI is a Ras-related small G-protein with a novel Nterminal extension that inhibits growth of ovarian and breast cancers. Oncogene 22:2897–2909
Yu Y, Luo R, Lu Z,Wei FengW, Badgwell D, Issa JP, Rosen DG, Liu J, Bast RC Jr, 2006, Biochemistry and biology of ARHI, DIRAS3), an imprinted tumor suppressor gene whose expression is lost in ovarian and breast cancers. Methods Enzymol 407:455–468
Wang L, Hoque A, Luo RZ, Yuan J, Lu Z, Nishimoto A, Liu J, Sahin AA, Lippman SM, Bast RC Jr, Yu Y, 2003, Loss of the expression of the tumor suppressor gene ARHI is associated with progression of breast cancer. Clin Cancer Res 9:3660–3666
Rosen DG,Wang L, Jain AN, Lu KH, Luo RZ, Yu Y, Liu J, Bast RC Jr, 2004, Expression of the tumor suppressor gene ARHI in epithelial ovarian cancer is associated with increased expression of p21WAF1/ CIP1 and prolonged progression-free survival. Clin Cancer Res 10: 6559–6566
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Hisatomi H, Nagao K, Wakita K, Kohno N, 2002, ARHI/NOEY2 inactivation may be important in breast tumor pathogenesis. Oncology 62:136–140
FengW, Marquez RT, Lu Z, Liu J, Lu KH, Issa JP, Fishman DM, Yu Y, Bast RC Jr, 2008, Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Cancer 112: 1489–1502
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Huang J, Lin Y, Li L, Qing D, Teng XM, Zhang YL, Hu X, Hu Y, Yang P, Han ZG, 2009, ARHI, as a novel suppressor of cell growth and downregulated in human hepatocellular carcinoma, could contribute to hepatocarcinogenesis. Mol Carcinog 48:130–140
Yang J, Hu A, Wang L, Li B, Chen Y, ZhaoW, XuW, Li T, 2009, NOEY2 mutations in primary breast cancers and breast hyperplasia. Breast 18:197–203
Janssen EA, Ovestad IT, Skaland I, Soiland H, Gudlaugsson E, Kjellevold KH, Nysted A, Soreide JA, Baak JP, 2009, LOH at 1p31, ARHI, and proliferation in lymph node-negative breast cancer. Cell Oncol 31:335–343
Yu Y, Fujii S, Yuan J, Luo RZ,Wang L, Bao J, KadotaM, Oshimura M, Dent SR, Issa JP, Bast RC Jr, 2003, Epigenetic regulation of ARHI in breast and ovarian cancer cells. Ann N Y Acad Sci 983: 268–277
Pei XH, Yang Z, Liu HX, Qiao SS, 2011, Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft. Cell Biol Int 35:1019–1024
Zhao X, Li J, Zhuo J, Cai L, 2010, Reexpression of ARHI inhibits tumor growth and angiogenesis and impairs the mTOR/VEGF pathway in hepatocellular carcinoma. Biochem Biophys Res Commun 403:417–421
Park WS, Cho YG, Kim CJ, Song JH, Lee YS, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, 2005, Hypermethylation of the RUNX3 gene in hepatocellular carcinoma. Exp Mol Med 37:276–281
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1277
EP 1279
DI 10.1007/s12253-015-9924-9
PG 3
ER
PT J
AU Jo, SY
Kim, SM
Lee, HS
Yoo, JN
AF Jo, Sol Yun
Kim, Sung Min
Lee, Hyung Sug
Yoo, Jin Nam
TI Mutational Heterogeneity of MED23 Gene in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Yoo, JN (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM goldfish@catholic.ac.kr
CR Poss ZC, Ebmeier CC, Taatjes DJ, 2013, TheMediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48:575–608
Makinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, Gentile M, Yan J, Enge M, Taipale M, Aavikko M, Katainen R, Virolainen E, Bohling T, Koski TA, Launonen V, Sjoberg J, Taipale J, Vahteristo P, Aaltonen LA, 2011, MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 334:252–255
LimWK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND,McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT, 2014, Exome sequencing identifies highly recurrentMED12 somatic mutations in breast fibroadenoma. Nat Genet 46:877–880
Yang X, Zhao M, Xia M, Liu Y, Yan J, Ji H, Wang G, 2012, Selective requirement forMediator MED23 in Ras-active lung cancer. Proc Natl Acad Sci U S A 109:E2813–E2822
Guo Y,Wang J, Li H, Liu W, Chen D, Zhao K, Liang X, Zhang Q, Yang Y, Chen G, 2015, MED23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma. J Gastroenterol Hepatol 30:1094–1103
Shi J, Han Q, Zhao H, Zhong C, Yao F, 2014, Downregulation of MED23 promoted the tumorigenecity of esophageal squamous cell carcinoma. Mol Carcinog 53:833–840
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Calin GA, Gafa R, Tibiletti MG, Herlea V, Becheanu G, Cavazzini L, Barbanti-Brodano G, Nenci I, Negrini M, Lanza G, 2000, Genetic progression in microsatellite instability high, MSI-H, colon cancers correlates with clinicopathological parameters: a study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes. Int J Cancer 89: 230–235
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2015
VL 21
IS 4
BP 1281
EP 1282
DI 10.1007/s12253-015-9959-y
PG 2
ER
PT J
AU Halasz, T
Horvath, G
Kiss, A
Par, G
Szombati, A
Gelley, F
Nemes, B
Kenessey, I
Piurko, V
Schaff, Zs
AF Halasz, Tunde
Horvath, Gabor
Kiss, Andras
Par, Gabriella
Szombati, Andrea
Gelley, Fanni
Nemes, Balazs
Kenessey, Istvan
Piurko, Violetta
Schaff, Zsuzsa
TI Evaluation of Histological and non-Invasive Methods for the Detection of Liver Fibrosis: The Values of Histological and Digital Morphometric Analysis, Liver Stiffness Measurement and APRI Score
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liver fibrosis; Liver stiffness; Digital morphometric analysis; Liver biopsy
ID Liver fibrosis; Liver stiffness; Digital morphometric analysis; Liver biopsy
AB Prognosis and treatment of liver diseases mainly depend on the precise evaluation of the fibrosis. Comparisons were made between the results of Metavir fibrosis scores and digital morphometric analyses (DMA), liver stiffness (LS) values and aminotransferase-platelet ratio (APRI) scores, respectively. Liver biopsy specimens stained with Sirius red and analysed by morphometry, LS and APRI measurements were taken from 96 patients with chronic liver diseases (56 cases of viral hepatitis, 22 cases of autoimmune- and 18 of mixed origin). The strongest correlation was observed between Metavir score and DMA (r=0.75 p<0.05), followed in decreasing order by LS and Metavir (r=0.61), LS and DMA (r=0.47) LS and APRI (r=0.35) and Metavir and APRI (r= 0.24), respectively. DMA is a helpful additional tool for the histopathological evaluation of fibrosis, even when the sample size is small and especially in case of advanced fibrosis. The non-invasive methods showed good correlation with the histopathological methods; LS proved to be more accurate than APRI. The stronger correlation between LS values and Metavir scores, as well as the results of DMA in case of appropriate sample size were remarkable.
C1 [Halasz, Tunde] Semmelweis University, 2nd Department of Pathology, Ulloi str 93, 1091 Budapest, Hungary.
[Horvath, Gabor] Hepatology Center of BudaBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi str 93, 1091 Budapest, Hungary.
[Par, Gabriella] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Szombati, Andrea] Del-Pesti CentrumkorhazBudapest, Hungary.
[Gelley, Fanni] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Nemes, Balazs] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi str 93, 1091 Budapest, Hungary.
[Piurko, Violetta] Semmelweis University, 2nd Department of Pathology, Ulloi str 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi str 93, 1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM schaff.zsuzsa@med.semmelweis-univ.hu
CR Bedossa P, Dargere D, Paradis V, 2003, Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 38:1449–1457
Afdhal NH, 2004, Biopsy or biomarkers: is there a gold standard for diagnosis of liver fibrosis? Clin Chem 50:1299–1300
Desmet VJ, Gerber M, Hoofnagle JH et al, 1994, Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19: 1513–1520
Germani G, Burroughs AK, Duillon AP, 2010, The relationship between liver disease stage and liver fibrosis: a tangled web. Histopathology 57:773–784
Huang Y, de Boer WB, Adams LA et al, 2014, Image analysis of liver biopsy samples measures fibrosis and predicts clinical outcome. J Hepatol 61:22–27
Hall AR, Tsochatzis E, Morris R et al, 2013, Sample size requirement for digital image analysis of collagen prportionate area in cirrhotic livers. Histopathology 62:421–430
Isgro G, Calvaruso V, Andreana L et al, 2013, The relationship between transient elastograpy and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis. J Gastroenterol 48:921–929
Huang Y, de Boer WB, Adams LA et al, 2013, Image analysis of liver collagen using sirius red is more accurate and correlates better with serum fibrosis markers than trichrome. Liver Int 338:1249– 1256
Poynard T, Bedossa P, Opolon P, 1997, Natural history of liver fibrosis progression in patient with chronic hepatitis C. The OBSVIRC, METAVIR, CLINVIR and DOSVIRCgroups. Lancet 349:825–832
Corpechot C, El Naggar A, Poujol-Robert A et al, 2006, Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology 43:1118–1124
Brunt M, Janney CG, Di Bisceglie AM et al, 1999, Nonacoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474
Ishak K, Baptista L, Bianchi L et al, 1995, Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699
Wai CT, Greenson JK, Fontana RJ, 2003, A simple noninvasive index can predict both significant fibrosis and cirrhosis in patient with chronic hepatitis C. Hepatology 38:518–526
Dahab GM, Kheriza MM, El-Beltagi HM et al, 2004, Digital quatification of fibrosis in liver biopsy sections: description of a new method by photoshop software. J Gastroenterol Hepatol 19: 78–85
Goodman ZD, Stoddard AM, Bonkowsky HL et al, 2009, Fibrosis progression in chronic hepatitis C: morphometric image analysis in the HALT-C trial. Hepatology 50:1738–1749
Huss S, Schmitz J, Goltz D et al, 2010, Development and evaluation of an open source Delphi-based software for morphometric quantification of liver fibrosis. Fibrogenesis Tissue Repair 3:10
Wright M, Thursz M, Pullen R et al, 2003, Quantitative versus morphological assessment of liver fibrosis: semi-quantitative scores aremore robust than digital image fibrosis area estimation. Liver Int 23:28–34
Maduli E, Andorno S, Rigamonti C et al, 2002, Evaluation of liver fibrosis in chronic hepatits C with a computer-assisted morphometric method. Ann Ital Med Int 17:242–247
Arima M, Terao H, Kashima K et al, 2004, Regression of liver fibrosis in cases of chronic liver disease type C: quantitative evaluation by using computed image analysis. Intern Med 43:902–910
FriedenbergMA,Miller L, Chung CYet al, 2005, Simplified method of hepatic fibrosis quantification: design of a new morphometric analysis application. Liver Int 25:1156–1161
O’BrienMJ, KeatingNM, Elderiny S et al, 2000, An assessment of digital image analysis to measure fibrosis in liver biopsy specimens of patients with chronic hepatitis C. Am J Clin Pathol 114:712–718
Pilette C, Rousselet C, Bedossa P et al, 1998, Histopathological evaluation of liver fibrosis: quantitative image analysis vs semiquantitative scores. Comparison with serum markers J Hepatol 28:439–446
Ziol M, Kettaneh A, Ganne-Carrie N et al, 2009, Relationships between fibrosis amounts assessed by morphometry and liver stiffness measurements in chronic hepatitis or steatohepatitis. Eur J Gastroenterol Hepatol 21:1261–1268
Lazzarini AL, Levine RA, Ploutz-Synder J et al, 2005, Advances in digital quantification technique enhance discrimination between mild and advanced liver fibrosis in chronic hepatitis C. Liver Int 25:1142–1149
Cho HJ, Seo YS, Lee KG et al, 2011, Serum aminotransferase levels instead of etiology affects the accuracy of transient elastography in chronic viral hepatitis patient. Gastroenterol Hepatol 26:492–500
Yasuda M, Shimizu I, Shiba M et al, 1999, Supressive efects of estradiol on dimetylnitrosamine-induced fibrosis of the liver in rats. Hepatology 29:719–727
Fraquelli M, Rigamonti C, Casazza G et al, 2007, Reproducibility of transient elastograpy in the evaluation of liver fibrosis in patient with chronic liver disease. Gut 56:968–973
Arena U, Vizutti F, Abraldes JG et al, 2008, Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatits C. Gut 57:1288–1293
Tapper EB, Cohen EB, Afdhal N et al, 2012, Levels of alanine aminotransferase confound use of transient elastography to diagnose fibrosis in patients with chronic HCV infection. Clin Gastroenterol Hepatol 10:932–937
McCormick SE, Goodman ZD, Maydonovitch CC et al, 1996, Evaluation of liver histology ALT elevation and HCV RNA titer in patients with chronic hepatitis C. Am J Gastroenterol 91:1516–1522
Poynard T, Ngo Y, Perazzo H et al, 2011, Prognostic value of liver fibrosis biomarkers. Ameta-analysis. Gastroenterol Hepatol 7:445– 454
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 1
EP 6
DI 10.1007/s12253-015-9964-1
PG 6
ER
PT J
AU Zhou, L
Li, J
Shao, QQ
Guo, JCh
Liang, ZY
Zhou, WX
Zhang, TP
You, L
Zhao, YP
AF Zhou, Li
Li, Jian
Shao, Qian-Qian
Guo, Jun-Chao
Liang, Zhi-Yong
Zhou, Wei-Xun
Zhang, Tai-Ping
You, Lei
Zhao, Yu-Pei
TI Expression and Significances of MTSS1 in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastasis suppressor 1; Pancreatic cancer; Lymph node metastasis; Prognosis
ID Metastasis suppressor 1; Pancreatic cancer; Lymph node metastasis; Prognosis
AB Thus far, expression of metastasis suppressor 1 (MTSS1), its clinicopathologic and prognostic significances in pancreatic cancer (PC) remain unknown. Expression of MTSS1 was detected by Western blotting in PC cell lines, and by tissue microarray-based immunohistochemical staining in paired tumor and non-tumor samples from 242 patients with PC. Furthermore, the correlations between MTSS1 expression and clinicopathologic variables as well as overall survival were evaluated. In PC cell lines, MTSS1 was differentially expressed. In addition, MTSS1 expression was significantly lower in tumor than in non-tumor tissues (P<0.001 in both McNemar and Mann–Whitney U tests). High tumoral expression of MTSS1 was closely associated with absence of lymph node metastasis (P=0.023). Univariate analysis found that high MTSS1 expression in tumor tissues was a strong predictor of favorable overall survival in the whole cohort (P<0.001). Besides, its impacts on prognosis were also observed in nine out of fourteen subgroups. Finally, MTSS1 expression was identified as an independent prognostic marker in the whole cohort (P=0.031) as well as in six subgroups (P<0.05), as shown by multivariate Cox regression test. Down-regulation of MTSS1 expression is evident in PC, and is associated with lymph node metastasis and poor prognosis.
C1 [Zhou, Li] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Li, Jian] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Shao, Qian-Qian] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Guo, Jun-Chao] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Liang, Zhi-Yong] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of Pathology, 100730 Beijing, China.
[Zhou, Wei-Xun] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of Pathology, 100730 Beijing, China.
[Zhang, Tai-Ping] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[You, Lei] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
[Zhao, Yu-Pei] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
RP Guo, JCh (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
EM gjcpumch@163.com
CR HidalgoM(2010, Pancreatic cancer. N Engl JMed 362:1605–1617
Egawa S, Toma H, Ohigashi H, Okusaka T, Nakao A, Hatori T, Maguchi H, Yanagisawa A, Tanaka M, 2012, Japan pancreatic cancer registry; 30th year anniversary: Japan pancreas society. Pancreas 41:985–992
Lee SR, Kim HO, Son BH, Yoo CH, Shin JH, 2013, Prognostic factors associated with long-term survival and recurrence in pancreatic adenocarcinoma. Hepatogastroenterology 60:358–362
Pongprasobchai S, Pannala R, Smyrk TC, BamletW, Pitchumoni S, Ougolkov A, de Andrade M, Petersen GM, Chari ST, 2008, Longterm survival and prognostic indicators in small, 25 % of cases. The E3 ubiquitin ligase NEDD4 (also known as NEDD4-1) has been reported to negatively regulate PTEN protein levels through poly-ubiquitination and proteolysis in carcinomas of the prostate, lung, and bladder, but its effect on PTEN in the breast has not been studied extensively. To investigate whether NEDD4 contributes to low PTEN levels in human breast cancer, we analyzed the expression of these proteins by immunohistochemistry across a large Swedish cohort of breast tumor specimens, and their transcript expression levels by microarrays. For both NEDD4 and PTEN, their transcript expression was significantly correlated to their protein expression. However, comparing NEDD4 expression to PTEN expression, either no association or a positive correlation was observed at the protein and transcript levels. This unexpected observation was further corroborated in two independent breast cancer cohorts from The Netherlands Cancer Institute and The Cancer Genome Atlas. Our results suggest that NEDD4 is not responsible for the frequent down-regulation of the PTEN protein in human breast carcinoma.
C1 [Chen, Yilun] Lund University, Department of Clinical Sciences, Division of Oncology and PathologyLund, Sweden.
[van de Vijver, J Marc] Academic Medical Center, Department of PathologyAmsterdam, The Netherlands.
[Hibshoosh, Hanina] Columbia University Medical CenterNew York, NY, USA.
[Parsons, Ramon] Icahn School of Medicine at Mount Sinai, Department of Oncological SciencesNew York, NY, USA.
[Saal, H Lao] Lund University, Department of Clinical Sciences, Division of Oncology and PathologyLund, Sweden.
RP Saal, HL (reprint author), Lund University, Department of Clinical Sciences, Division of Oncology and Pathology, Lund, Sweden.
EM lao.saal@med.lu.se
CR Maehama T, Dixon JE, 1998, The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biolumin Chemilumin 273:13375–13378
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Liaw D, Marsh DJ, Li J, Dahia PL,Wang SI, Zheng Z, et al, 1997, Germline mutations of the PTEN gene in cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64–67
Hobert JA, Eng C, 2009, PTEN hamartoma tumor syndrome: an overview. Genitourin Med 11:687–694
Li J, Yen C, Liaw D, Podsypanina K, Bose S,Wang SI, et al, 1997, PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947
Steck PA, PershouseMA, Jasser SA, Yung WK, Lin H, Ligon AH, et al, 1997, Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356–362
Shaw RJ, Cantley LC, 2006, Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441:424–430
Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, et al, 2015, COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res 43: D805–811
Saal LH, Holm K,Maurer M, Memeo L, Su T,Wang X, et al, 2005, PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65:2554–2559
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Saal LH, Gruvberger-Saal SK, Persson C, Lovgren K, Jumppanen M, Staaf J, et al, 2008, Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 40:102–107
Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, et al, 2007, NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128:129–139
Drinjakovic J, Jung H, Campbell DS, Strochlic L, Dwivedy A, Holt CE, 2010, E3 ligase Nedd4 promotes axon branching by downregulating PTEN. Neuron 65:341–357
Goh CP, Low LH, Putz U, Gunnersen J, Hammond V, Howitt J, et al, 2013, Ndfip1 expression in developing neurons indicates a role for protein ubiquitination by Nedd4 E3 ligases during cortical development. Neurosci Lett 555:225–230
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Trotman LC, Wang X, Alimonti A, Chen Z, Teruya-Feldstein J, Yang H, et al, 2007, Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128:141–156
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Eide PW, Cekaite L, Danielsen SA, Eilertsen IA, Kjenseth A, Fykerud TA, et al, 2013, NEDD4 is overexpressed in colorectal cancer and promotes colonic cell growth independently of the PI3K/PTEN/AKT pathway. Cell Signal 25:12–18
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van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al, 2002, A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009
van 't Veer, LJ, Dai, H, van de Vijver, MJ, He, YD, Hart, AA,Mao, M et al, 2002, Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536
Ahn Y, Hwang CY, Lee SR, Kwon KS, Lee C, 2008, The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4. Biochem J 412:331–338
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 41
EP 47
DI 10.1007/s12253-015-9971-2
PG 7
ER
PT J
AU Kucharczyk, T
Krawczyk, P
Powrozek, T
Kowalski, MD
Ramlau, R
Kalinka-Warzocha, E
Knetki-Wroblewska, M
Winiarczyk, K
Krzakowski, M
Milanowski, J
AF Kucharczyk, Tomasz
Krawczyk, Pawel
Powrozek, Tomasz
Kowalski, M Dariusz
Ramlau, Rodryg
Kalinka-Warzocha, Ewa
Knetki-Wroblewska, Magdalena
Winiarczyk, Kinga
Krzakowski, Maciej
Milanowski, Janusz
TI The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Pemetrexed monotherapy; TS; MTHFR; Polymorphism
ID Non-small cell lung cancer; Pemetrexed monotherapy; TS; MTHFR; Polymorphism
AB In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/ 3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/ C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) aswell as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.
C1 [Kucharczyk, Tomasz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Krawczyk, Pawel] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Powrozek, Tomasz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Kowalski, M Dariusz] M. Sklodowska-Curie in Warsaw, Oncology Centre-Institute, Department of Lung and Chest Cancer, W. K. Roentgena 5, 02-781 Warsaw, Poland.
[Ramlau, Rodryg] Greater Poland Center of Pulmonology and Thoracic Surgery of Eugenia and Janusz ZeylandPoznan, Poland.
[Kalinka-Warzocha, Ewa] Regional Centre of Oncology in Lodz, Ignacego Paderewskiego 4, 90-993 Lodz, Poland.
[Knetki-Wroblewska, Magdalena] M. Sklodowska-Curie in Warsaw, Oncology Centre-Institute, Department of Lung and Chest Cancer, W. K. Roentgena 5, 02-781 Warsaw, Poland.
[Winiarczyk, Kinga] M. Sklodowska-Curie in Warsaw, Oncology Centre-Institute, Department of Lung and Chest Cancer, W. K. Roentgena 5, 02-781 Warsaw, Poland.
[Krzakowski, Maciej] M. Sklodowska-Curie in Warsaw, Oncology Centre-Institute, Department of Lung and Chest Cancer, W. K. Roentgena 5, 02-781 Warsaw, Poland.
[Milanowski, Janusz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
RP Krawczyk, P (reprint author), Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, 20-954 Lublin, Poland.
EM krapa@poczta.onet.pl
CR Dela Cruz CS, Tanoue LT, Matthay RA, 2011, Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med 32:605–644
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 49
EP 56
DI 10.1007/s12253-015-9966-z
PG 8
ER
PT J
AU Sudsarn, P
Boonmars, Th
Ruangjirachuporn, W
Namwat, N
Loilome, W
Sriraj, P
Aukkanimart, R
Wonkchalee, N
Jiraporn, S
AF Sudsarn, Pakkayanee
Boonmars, Thidarut
Ruangjirachuporn, Wipaporn
Namwat, Nisana
Loilome, Watcharin
Sriraj, Pranee
Aukkanimart, Ratchadawan
Wonkchalee, Nadchanan
Jiraporn, Songsri
TI Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Praziquantel; Aspirin; Opisthorchis viverrini; N-nitrosodimethylamine; Cholangiocarcinoma; Syrian hamster
ID Praziquantel; Aspirin; Opisthorchis viverrini; N-nitrosodimethylamine; Cholangiocarcinoma; Syrian hamster
AB Opisthorchiasis is one of the major risk factors for cholangiocarcinoma (CCA) in northeastern Thailand. An effective drug for killing this parasite is praziquantel. Recently, several reports have shown that with frequent use, praziquantel may itself be a CCA risk and can cause liver cell damage from an immunopathological response after parasite death. Aspirin has many properties including antiinflammation and anti-cancer. Therefore, we use of aspirin (As) and praziquantel (Pz) to improve hepatobiliary system function in hamsters infected with Opisthorchis viverrini (OV) and or administered N-nitrosodimethylamine (ND). Livers of OVNDAsPz, appeared healthy macroscopically, suggesting slow progression of cholangiocarcinoma evident by extent of fibrosis and bile duct cell proliferation was less than OVND although aggregations of inflammatory cells remained. Proliferating cell nuclear antigen (PCNA), cytokeratin 19 (CK19), and cancer antigen (CA19-9) staining were strongly positive in OVND, but were only slight in OVNDAs. Moreover, OVNDAsPz, appeared a few inflammatory infiltrations, bile duct proliferation, fibrosis and CCA area than the OVNDAs group. Thirty seven point five percent of hamster in this group could not develop CCA. These findings suggest that using aspirin combination with praziquantel treatment can improve the hepatobiliary system after O. viverrini infection and reduce the risk of CCA.
C1 [Sudsarn, Pakkayanee] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Boonmars, Thidarut] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Ruangjirachuporn, Wipaporn] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
[Namwat, Nisana] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Loilome, Watcharin] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Sriraj, Pranee] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Aukkanimart, Ratchadawan] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Wonkchalee, Nadchanan] Khon Kaen University, Liver Fluke and Cholangiocarcinoma Research Center, 40002 Khon Kaen, Thailand.
[Jiraporn, Songsri] Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
RP Boonmars, Th (reprint author), Khon Kaen University, Faculty of Medicine, Department of Parasitology, 40002 Khon Kaen, Thailand.
EM bthida@kku.ac.th;boonmars@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 57
EP 65
DI 10.1007/s12253-015-9967-y
PG 9
ER
PT J
AU Wang, Qh
Ji, ZG
Li, Hz
Fan, H
Chen, Zg
Shi, Bb
Fang, Y
AF Wang, Qing-hai
Ji, Zhi-Gang
Li, Han-zhong
Fan, Hua
Chen, Zhi-gang
Shi, Bing-bing
Fang, Yujiang
TI Clinicopathologic Comparison of Urothelial Bladder Carcinoma in Young and Elder Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urothelial bladder cancer; Young; Pathology
ID Urothelial bladder cancer; Young; Pathology
AB Bladder cancer (BC) is a common aggressive malignancy and Urothelial bladder cancer (UBC) consists of the majority of BC. There is uncertainty regarding the clinicopathologic characteristics of UBCs in younger patients. To investigate the clinicopathologic features of young patients with UBCs. A total of 2825 pathological records of UBC patients, including 42 young patients (≤ 30 years old) and 2783 elder patients (> 30 years old), were retrospectively studied. The stage distribution classified was statistically significant (Χ2 = 12.25, P = 0.02) between young and old patients; superficial tumors was far more in young patients than in old patients. More young patients tended to be low- and moderate-grade UBCs (Χ2 = 6.75, P = 0.009). Young patients with superficial UBCs also showed lower recurrence rate, compared to elder patients (Χ2 = 5.77, P = 0.02). For 5-year survival rate, young patients (93.8 %) showed better than elder patients (85.1 %) (Χ2 = 4.01, P = 0.045). Patients younger than 30 years old with UBCs had low-grade and low-stage tumors and exhibited better prognosis than elder patients.
C1 [Wang, Qing-hai] the Affiliated Hospital of Qingdao University, Department of Kidney Transplantation, 1677 Wutaishan Road, 266000 Qingdao, China.
[Ji, Zhi-Gang] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 1 Shuaifuyuan, Wangfujing, 100730 Beijing, China.
[Li, Han-zhong] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 1 Shuaifuyuan, Wangfujing, 100730 Beijing, China.
[Fan, Hua] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 1 Shuaifuyuan, Wangfujing, 100730 Beijing, China.
[Chen, Zhi-gang] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 1 Shuaifuyuan, Wangfujing, 100730 Beijing, China.
[Shi, Bing-bing] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 1 Shuaifuyuan, Wangfujing, 100730 Beijing, China.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Shi, Bb (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 100730 Beijing, China.
EM shibbpumch@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 67
EP 70
DI 10.1007/s12253-015-9968-x
PG 4
ER
PT J
AU Horvath, BK
Pankovics, P
Kalman, E
Kadar, Zs
Battyani, Z
Lengyel, Zs
Reuter, G
AF Horvath, Barbara Katalin
Pankovics, Peter
Kalman, Endre
Kadar, Zsolt
Battyani, Zita
Lengyel, Zsuzsanna
Reuter, Gabor
TI Epidemiological, Clinicopathological and Virological Features of Merkel Cell Carcinomas in Medical Center of University of Pecs, Hungary (2007–2012)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Merkel cell polyomavirus; Merkel cell carcinoma; Skin tumour; DNA tumour virus
ID Merkel cell polyomavirus; Merkel cell carcinoma; Skin tumour; DNA tumour virus
AB Merkel cell carcinoma (MCC) is a rare, highly aggressive skin tumour. In 2008, a Merkel cell polyomavirus (MC) was identified in MCCs as a potential etiological factor of MCC. The aims of this retrospective study were to investigate the epidemiological, clinicopathological and virological features of MCCs. Between 2007 and 2012, 11 patients had been diagnosed with MCC by histological methods in University of Pecs, Hungary. In eight MCC cases MC was tested by PCR (in primary skin lesions, lymph nodes/cutan metastases, MCC neighboring carcinomas). Clinicopathological characteristics (age, histological pattern, lymphovascular invasion, co-morbidities) of MC-positive and MC-negative cases were compared. MC was detected in three (37.5 %) out of eight patients’ primary tumour or metastasis. The average age was 73.8 (64.3 in MC-positive group). Except the youngest, 55 year-old patient (the primary tumour appeared on his leg), all tumours were found at the head and neck region. Immunosuppression (steroid therapy, chronic lymphoid leukaemia, chronic obstructive pulmonary disease) and/or old age were characteristic for all cases. Histological pattern was different in MC-positive and in MC-negative groups: MCCs with MC showed more homogeneous histological pattern, lack of lymphovascular invasion and were associated with better prognosis (mortality rate: 33 % versus 80 %). MCC associated with oncogenic virus is a newly recognized clinical entity. However, MC could not be detected in all histologically proven MCCs. The well-defined selection of patients/ disease groups and better characterization of differences between MC-positive and negative cases is an important step towards the recognition of the etiology and pathogenesis of all MCCs.
C1 [Horvath, Barbara Katalin] ANTSZ Regional Institute of State Public Health Service, Regional Laboratory of Virology, Szabadsag ut 7, H-7623 Pecs, Hungary.
[Pankovics, Peter] ANTSZ Regional Institute of State Public Health Service, Regional Laboratory of Virology, Szabadsag ut 7, H-7623 Pecs, Hungary.
[Kalman, Endre] University of Pecs, Department of PathologyPecs, Hungary.
[Kadar, Zsolt] University of Pecs, Department of Dermatology, Venereology and OncodermatologyPecs, Hungary.
[Battyani, Zita] University of Pecs, Department of Dermatology, Venereology and OncodermatologyPecs, Hungary.
[Lengyel, Zsuzsanna] University of Pecs, Department of Dermatology, Venereology and OncodermatologyPecs, Hungary.
[Reuter, Gabor] ANTSZ Regional Institute of State Public Health Service, Regional Laboratory of Virology, Szabadsag ut 7, H-7623 Pecs, Hungary.
RP Reuter, G (reprint author), ANTSZ Regional Institute of State Public Health Service, Regional Laboratory of Virology, H-7623 Pecs, Hungary.
EM reuter.gabor@gmail.com
CR Woo SH, Stumpfova M, Jensen UB, Lumpkin EA, Owens DM, 2010, Identification of epidermal progenitors for the Merkel cell lineage. Development 137(23):3965–3971
Van Keymeulen A, Mascre G, Youseff KK, Harel I, Michaux C, De Geest N, Szpalski C, Achouri Y, BlochW, Hassan BA, Blanpain C, 2009, Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187(1):91– 100
HeathM, Jaimes N, Lemos B,Mostaghimi A,Wang LC, Penas PF, Nghiem P, 2008, Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 58(3):375–381
Feng H, ShudaM, Chang Y, Moore PS, 2008, Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100
Lemos BD, Storer BE, Iyer JG, Phillips JL, Bichakjian CK, Fang LC, Johnson TM, Liegeois-Kwon NJ, Otley CC, Paulson KG, Ross MI, Yu SS, Zeitouni NC, Byrd DR, Sondak VK, Gershenwald JE, Sober AJ, Nghiem P, 2010, Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol 63(5):751–761
Becker JC, Houben R, Uqurel S, Trefzer U, Pfohler C, Schrama D, 2009, MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 129(1):248–250
Varga E, Kiss M, Szabo K, Kemeny L, 2009, Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas. Br J Dermatol 161(4):930–932
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Laude HC, Jonchere B, Maubec E, Carlotti A, Marinho E, Couturaud B, Peter M, Sastre-Garau X, Avril MF, Duprin N, Rozenberg F, 2010, Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma. PLoS Pathog 6(8):e1001076
Bhatia K, Goedert JJ, Modali R, Preiss L, Ayers LW, 2010, Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral abundance and better clinical outcome. Int J Cancer 127(6):1493–1496
Waltari M, Sihto H, Kukko H, Koljonen V, Sankila R, Bohling T, Joensuu H, 2011, Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma. Int J Cancer 129(3):619–628
Busam KJ, Jungbluth AA, Rekthman N, Coit D, PulitzerM, Bini J, Arora R, Hanson NC, Tassello JA, Frosina D, Moore P, Chang Y, 2009)Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol 33(9):1378–1385
Martel-Jantin C, Filippone C, Cassar O, Peter M, Tomasic G, Vielh P, Briere J, Petrella T, Aubriot-Lorton MH, Mortier L, Jouvion G, Sastre-GarauX, Robert C,GessainA(2012, Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma. Virology 426(2):134–142
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 71
EP 77
DI 10.1007/s12253-015-9974-z
PG 7
ER
PT J
AU Tarnoki, LD
Tarnoki, DA
Ohlmann-Knafo, S
Pickuth, D
AF Tarnoki, Laszlo David
Tarnoki, Domonkos Adam
Ohlmann-Knafo, Susanne
Pickuth, Dirk
TI Pattern of Tumour Spread of Common Primary Tumours as Seen on Magnetic Resonance Imaging
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Breast tumor; Vertebral metastasis; Spine; Pedicle
ID Lung cancer; Breast tumor; Vertebral metastasis; Spine; Pedicle
AB Although some reports with computed tomography and bone scintigraphy are available in the literature, the distinct epidemiologic description of skeletal metastatic pattern of various tumors is still lacking. This study uses a novel approach to identify skeletal metastases from magnetic resonance imaging (MRI) data to describe metastatic pattern in common malignancies. A retrospective analysis of 130 cancer patients (42 lung, 56 breast, 11 prostate cancers; 21 multiple myeloma) with vertebral metastases and without disseminated disease, and whom underwent a whole body 3Tesla MRI investigation (Discovery MR750w), was carried out. Multiple myeloma had the most commonly disseminated metastatic disease (95 %) compared to lung (28 %), breast (44 %) and prostate (71 %) cancers. Lung cancer was related to more frequent pedicle involvement compared to breast or prostate cancer (29, 9 and 0 %, p<0.05). Pathologic fracture was mainly associated with multiple myeloma (43 %). The prevalence of lung cancer metastases was more frequent in the lumbal spine (81 %), as well as particular in C7, D7, D8, D9 and L1, compared to breast cancers. Most differences among tumors were detected in the extravertebral osseous metastatic pattern (p<0.05). The highest frequency of extravertebral skeletal metastases was present in multiple myeloma (28 to 76 %). Brain metastasis was more frequent in lung cancer compared to breast cancers (35 % vs. 17 %, p<0.05). Significant differences in the skeletal metastatic pattern among common malignancies were demonstrated with MRI.
C1 [Tarnoki, Laszlo David] Caritasklinikum Saarbrucken St. Theresia, Academic Teaching Hospital of Saarland University, Department of Diagnostic and Interventional Radiology, Rheinstraße 2, D-66113 Saarbrucken, Germany.
[Tarnoki, Domonkos Adam] Caritasklinikum Saarbrucken St. Theresia, Academic Teaching Hospital of Saarland University, Department of Diagnostic and Interventional Radiology, Rheinstraße 2, D-66113 Saarbrucken, Germany.
[Ohlmann-Knafo, Susanne] Caritasklinikum Saarbrucken St. Theresia, Academic Teaching Hospital of Saarland University, Department of Diagnostic and Interventional Radiology, Rheinstraße 2, D-66113 Saarbrucken, Germany.
[Pickuth, Dirk] Caritasklinikum Saarbrucken St. Theresia, Academic Teaching Hospital of Saarland University, Department of Diagnostic and Interventional Radiology, Rheinstraße 2, D-66113 Saarbrucken, Germany.
RP Tarnoki, LD (reprint author), Caritasklinikum Saarbrucken St. Theresia, Academic Teaching Hospital of Saarland University, Department of Diagnostic and Interventional Radiology, D-66113 Saarbrucken, Germany.
EM tarnoki4@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 79
EP 85
DI 10.1007/s12253-015-9975-y
PG 7
ER
PT J
AU Soylu, H
Acar, N
Ozbey, O
Unal, B
Koksal, TI
Bassorgun, I
Ciftcioglu, A
Ustunel, I
AF Soylu, Hakan
Acar, Nuray
Ozbey, Ozlem
Unal, Betul
Koksal, Turker Ismail
Bassorgun, Ibrahim
Ciftcioglu, Akif
Ustunel, Ismail
TI Characterization of Notch Signalling Pathway Members in Normal Prostate, Prostatic Intraepithelial Neoplasia (PIN) and Prostatic Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunohistochemistry; Notch signalling pathway; Prostate cancer; Prostatic intraepithelial neoplasia
ID Immunohistochemistry; Notch signalling pathway; Prostate cancer; Prostatic intraepithelial neoplasia
AB Prostate Cancer (PCa) holds the second place in terms of cancer-related mortality rate among men. The Notch signalling pathway regulates the proliferation and differentiation in embryonic and adult tissues and determines the cell fate. The body of knowledge in the present literature is currently controversial about the effect of the Notch pathway on prostatic cancer. Therefore, the present study aimed to examine the immunolocalization and expression levels of Notch1- 4, Jagged1-2, Delta, HES1 and HES5 from among the members of the Notch signalling pathway in tissues of normal, prostatic intraepithelial neoplasia (PIN) and malignant prostate. The current study included a sample of 20 patients with localised prostatic adenocarcinoma, 18 patients with high grade PIN (H-PIN) and 18 normal prostatic tissue. Immunolocalisations of Notch1, 2, 3, 4, Jagged1, 2, Delta, HES1 and HES5 were identified through the immunohistochemical method. The findings of the present study showed that all in-scope members of the Notch signalling pathway were localised in PIN structures to a greater extent than in other tissues and from amongst these members, specifically Notch1, Notch4, Jagged1 and HES1 were at more significant levels. Consequently, the findings of the present study may indicate that the Notch signalling pathway can play a role especially in the formation of PIN structures.
C1 [Soylu, Hakan] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
[Acar, Nuray] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
[Ozbey, Ozlem] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
[Unal, Betul] Akdeniz University, Faculty of Medicine, Department of Pathology, 07070 Antalya, Turkey.
[Koksal, Turker Ismail] Akdeniz University, Faculty of Medicine, Department of Urology, 07070 Antalya, Turkey.
[Bassorgun, Ibrahim] Akdeniz University, Faculty of Medicine, Department of Pathology, 07070 Antalya, Turkey.
[Ciftcioglu, Akif] Akdeniz University, Faculty of Medicine, Department of Pathology, 07070 Antalya, Turkey.
[Ustunel, Ismail] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
RP Ustunel, I (reprint author), Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
EM iustunel@akdeniz.edu.tr
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WangX, FuY, ChenX, Ye J, LuB, Ye F, LuW, XieX(2010, The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol 136(7):989–996., DOI 10.1007/s00432-009-0744-8
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 87
EP 94
DI 10.1007/s12253-015-9983-y
PG 8
ER
PT J
AU Melling, N
Grimm, N
Simon, R
Stahl, P
Bokemeyer, C
Terracciano, L
Sauter, G
Izbicki, RJ
Marx, HA
AF Melling, Nathaniel
Grimm, Norbert
Simon, Ronald
Stahl, Philip
Bokemeyer, Carsten
Terracciano, Luigi
Sauter, Guido
Izbicki, R Jakob
Marx, H Andreas
TI Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tissue microarray; Gastrointestinal cancer; Colorectal cancer; Biomarker
ID Tissue microarray; Gastrointestinal cancer; Colorectal cancer; Biomarker
AB To correlate H2Bub1 expression with outcome in colorectal cancer, H2Bub1 expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinicopathological parameters. H2Bub1 IHC was seen in 1256 (79.3 %) of 1584 interpretable CRC and was considered weak in 26.2 % and strong in 53.1% of cancers. H2Bub1 expression was completely lost in 20.7 % of the cases. Loss of H2Bub1 expression was associated with high tumor grade (p = 0.0211), high tumor stage (p = 0.0003), positive nodal status (p = 0.0139) and histological tumor type (p = 0.0202). No link was found between H2Bub1 expression and tumor localization (p = 0.1262), peritumoral lymphocytic infiltration (p = 0.2523) or vascular invasion (p = 0.5970). Loss of H2Bub1 expression in CRC was strongly associated with poor patient survival (p = 0.0006). This observation held true also in a subset survival analysis of nodal negative (N0) and nodal positive (N1) cancers (p = 0.0296 and p = 0.0197, respectively). In the subgroup of p53 negative cancers no prognostic impact of H2Bub1 staining was seen (p = 0.1924), whereas in p53 positive CRC H2Bub1 expression loss was associated with poor prognosis (p = 0.0031). Strikingly worsened outcome was found for nodal negative cancers presenting with accumulation of p53 when H2Bub1 expression was lost (p = 0.0006). Our data demonstrate that a reduced H2Bub1 expression is a strong prognostic biomarker both in nodal negative and nodal positive CRC. H2Bub1 expression measurement might help to select nodal negative CRC patients that may benefit from adjuvant therapy.
C1 [Melling, Nathaniel] University Medical Center Hamburg-Eppendorf, Department of Surgery, 20246 Hamburg, Germany.
[Grimm, Norbert] Regio Hosptital Pinneberg, Department of Surgery, 25421 Pinneberg, Germany.
[Simon, Ronald] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Stahl, Philip] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Bokemeyer, Carsten] University Medical Center Hamburg-Eppendorf, Hubertus Wald Cancer Center, Department of Oncology, Hematology, BMT with section Pneumology, 20246 Hamburg, Germany.
[Terracciano, Luigi] University Hospital Basel, Institute of Pathology, 4001 Basel, Switzerland.
[Sauter, Guido] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
[Izbicki, R Jakob] University Medical Center Hamburg-Eppendorf, Department of Surgery, 20246 Hamburg, Germany.
[Marx, H Andreas] University Medical Center Hamburg Eppendorf, Pathology, Martinistrasse 52, 20246 Hamburg, Germany.
RP Marx, HA (reprint author), University Medical Center Hamburg Eppendorf, Pathology, 20246 Hamburg, Germany.
EM a.marx@uke.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 95
EP 102
DI 10.1007/s12253-015-9977-9
PG 8
ER
PT J
AU Qingxu, G
Yan, Z
Jiannan, X
Yunlong, L
AF Qingxu, Guo
Yan, Zhang
Jiannan, Xu
Yunlong, Liu
TI Association Between the Gene Polymorphisms of HDAC9 and the Risk of Atherosclerosis and Ischemic Stroke
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Histone deacetylase 9; Atherosclerosis; Ischemic stroke; Polymorphism
ID Histone deacetylase 9; Atherosclerosis; Ischemic stroke; Polymorphism
AB Genome-wide association studies have demonstrated various polymorphisms of histone deacetylase 9 (HDAC9) gene was strong risk locus for large-vessel stroke, but the results were controversial. This study aims to replicate the association between the previous detected SNPs of HDAC9 and the susceptibility of ischemic stroke. The study population consisted of 262 consecutive patients diagnosed with ischemic stroke and 300 age and gender matched unrelated controls between October 2012 and October 2014. Rs11984041, rs2389995, and rs2240419 of HDAC9 were genotyped and compared between the cases and controls. The SNP rs11984041 of HDAC9 was found nonpolymorphic in the population involved. The G allele of rs2389995 was found significantly associated with decreased risk of ischemic stroke, no matter with the codominant (AG v.s AA, 0.53 (0.36–0.77), P < 0.001; GG v.s AA, 0.63 (0.27–1.43), P < 0.001), dominant (AG + GG v.s AA, 0.54 (0.38–0.78), P < 0.001), or the recessive model (GG vs AA + AG, 0.75 (0.33–1.71), P < 0.001). On the other hand, The T allele of rs2240419 was found significantly associated with increased risk of ischemic stroke, no matter with the codominant (CT v.s CC, 1.75 (1.22–2.51), P < 0.001; TT v.s CC, 2.67 (1.55–4.61), P < 0.001), dominant (CT + TT v.s CC, 1.93 (1.38–2.71), P < 0.001), or the recessive model (TT vs CC + CT, 2.07 (1.23–3.47), P < 0.001). No linkage disequilibrium was found between rs2389995 and rs2240419 of HDAC9. In conclusion, the present study demonstrated the SNP rs11984041 of HDAC9 was nonpolymorphic in Chinese Han population. The minor G allele of rs2389995 significantly decreased and the minor Tallele of rs2240419 significantly increased the risk of ischemic stroke.
C1 [Qingxu, Guo] The General Hospital of Beijing Military Region, Department of Vascular Surgery, No.5 NancangmenBeijing, China.
[Yan, Zhang] The General Hospital of Beijing Military Region, Ophthalmology DepartmentBeijing, China.
[Jiannan, Xu] Yanjiao People’s Hospital, Department of CardiologyHebei, China.
[Yunlong, Liu] The General Hospital of Beijing Military Region, Department of Vascular Surgery, No.5 NancangmenBeijing, China.
RP Yunlong, L (reprint author), The General Hospital of Beijing Military Region, Department of Vascular Surgery, Beijing, China.
EM liuyunlong_dragon@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 103
EP 107
DI 10.1007/s12253-015-9978-8
PG 5
ER
PT J
AU Huang, CF
Deng, WW
Zhang, L
Zhang, WF
Sun, ZJ
AF Huang, Cong-Fa
Deng, Wei-Wei
Zhang, Lu
Zhang, Wen-Feng
Sun, Zhi-Jun
TI Expression of LC3, LAMP2, KEAP1 and NRF2 in Salivary Adenoid Cystic Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LC3; LAMP2; KEAP1; NRF2; Salivary adenoid cystic carcinoma
ID LC3; LAMP2; KEAP1; NRF2; Salivary adenoid cystic carcinoma
AB Salivary Adenoid Cystic Carcinoma (SACC) is a tumor characterized by inevitable local progression and terminal hematogenous metastasis. This study aimed to investigate the expression of LC3, LAMP2, KEAP1 and NRF2 in SACC. Human salivary gland tissue microarray which contains 74 SACC, 12 pleomorphic adenoma and 18 normal salivary gland specimens. High expression of LC3, LAMP2, KEAP1 and NRF2 were found in SACC patients, and LC3, LAMP2, KEAP1 and NRF2 expression were significantly higher in SACC than as compared with pleomorphic adenoma and (or) normal salivary gland. The expression of NRF2 was correlated with pathological type of human SACC (P < 0.05). Moreover, the high-expression of KEAP1 had significant correlations with LC3 (P < 0.001, R = 0.3195), and LAMP2 (P < 0.001, R = 0.3346) and NRF2 (P < 0.05, R = 0.2246) by using the Pearson correlation coefficient test. Our findings demonstrated that up-regulation of LC3, LAMP2, KEAP1 and NRF2 were associated with carcinogenesis and progression of SACC patients, suggesting that they may be useful molecular targets in salivary adenoid cystic carcinoma.
C1 [Huang, Cong-Fa] Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 37 Luoyu Road, 430079 Wuhan, China.
[Deng, Wei-Wei] Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 37 Luoyu Road, 430079 Wuhan, China.
[Zhang, Lu] Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 37 Luoyu Road, 430079 Wuhan, China.
[Zhang, Wen-Feng] Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 37 Luoyu Road, 430079 Wuhan, China.
[Sun, Zhi-Jun] Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 37 Luoyu Road, 430079 Wuhan, China.
RP Zhang, WF (reprint author), Wuhan University, School and Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, 430079 Wuhan, China.
EM zhangwf59@163.com
CR Wang YF, ZhangW, He KF, Liu B, Zhang L, et al., 2014, Induction of autophagy-dependent cell death by the survivin suppressant YM155 in salivary adenoid cystic carcinoma. Apoptosis 19:748– 758
Tang QL, Fan S, Li HG, Chen WL, Shen XM, et al., 2011, Expression of Cyr61 in primary salivary adenoid cystic carcinoma and its relation to Ki-67 and prognosis. Oral Oncol 47:365–370
Munafo DB, Colombo MI, 2001, A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. J Cell Sci 114:3619–3629
Meijer AJ, Dubbelhuis PF, 2004, Amino acid signalling and the integration of metabolism. Biochem Biophys Res Commun 313: 397–403
Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, et al., 2008, Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4:151–175
Saha T, 2012, LAMP2A overexpression in breast tumors promotes cancer cell survival via chaperone-mediated autophagy. Autophagy 8:1643–1656
Fehrenbacher N, Bastholm L, Kirkegaard-Sorensen T, Rafn B, Bottzauw T, et al., 2008, Sensitization to the lysosomal cell death pathway by oncogene-induced down-regulation of lysosomeassociated membrane proteins 1 and 2. Cancer Res 68:6623–6633
Miracco C, Cevenini G, Franchi A, Luzi P, Cosci E, et al., 2010, Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions. Hum Pathol 41:503–512
Tang JY, Hsi E, Huang YC, Hsu NC, Chu PY, et al., 2013, High LC3 expression correlates with poor survival in patients with oral squamous cell carcinoma. Hum Pathol 44:2558–2562
Eskelinen EL, 2011, The dual role of autophagy in cancer. Curr Opin Pharmacol 11:294–300
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Takaya K, Suzuki T, Motohashi H, Onodera K, Satomi S, et al., 2012, Validation of the multiple sensor mechanism of the Keap1- Nrf2 system. Free Radic Biol Med 53:817–827
Leinonen HM, Kansanen E, Polonen P, Heinaniemi M, Levonen AL, 2014, Role of the keap1-nrf2 pathway in cancer. Adv Cancer Res 122:281–320
Huang CF, Zhang L, Ma SR, Zhao ZL, Wang WM, et al., 2013, Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma. PLoS One 8: e83479
Liu C, Xu P, Chen D, Fan X, Xu Y, et al., 2013, Roles of autophagy-related genes beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia. Biomed Rep 1:855–860
Jiang L, Huang S, LiW, ZhangD, Zhang S, et al., 2012, Expression of autophagy and ER stress-related proteins in primary salivary adenoid cystic carcinoma. Pathol Res Pract 208:635–641
Mello AS, Goldim MP, Mezzalira J, Garcia CS, Daitx VV, et al., 2014, LAMP2 as a marker of EBV-mediated B lymphocyte transformation in the study of lysosomal storage diseases. Mol Cell Biochem 385:1–6
Kansanen E, Kuosmanen SM, Leinonen H, Levonen AL, 2013, The Keap1-Nrf2 pathway: mechanisms of activation and dysregulation in cancer. Redox Biol 1:45–49
Suzuki T, Motohashi H, Yamamoto M, 2013, Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci 34: 340–346
Lister A, Nedjadi T, Kitteringham NR, Campbell F, Costello E, et al., 2011, Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy. Mol Cancer 10:37
Gonzalez-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, et al., 2005, The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 118:3091–3102
Tanida I, Tanida-Miyake E, Ueno T, Kominami E, 2001, The human homolog of Saccharomyces cerevisiae Apg7p is a proteinactivating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J Biol Chem 276:1701–1706
Gonzalez Y, Aryal B, Chehab L, Rao VA, 2014, Atg7- and Keap1- dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress. Oncotarget 5:1526–1537
Huber S, Valente S, Chaimbault P, Schohn H, 2014, Evaluation of 2-pioglitazone, an analogue of pioglitazone, on colon cancer cell survival: evidence of drug treatment association with autophagy and activation of the Nrf2/Keap1 pathway. Int J Oncol 45:426–438
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 109
EP 114
DI 10.1007/s12253-015-9981-0
PG 6
ER
PT J
AU Markow, M
Bui, MM
Lin, HY
Lloyd, M
Sexton, JW
Dhillon, J
AF Markow, Michael
Bui, M Marilyn
Lin, Hui-Yi
Lloyd, Mark
Sexton, J Wade
Dhillon, Jasreman
TI Evaluation of PAX8 Expression and Its Potential Diagnostic and Prognostic Value in Renal and Extra-Renal Ewing Sarcomas/PNETs
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PAX8; PNET; Renal PNET
ID PAX8; PNET; Renal PNET
AB PAX8 is a transcription factor involved in the regulation of organogenesis of the thyroid gland, kidney, and Mullerian system. It is commonly expressed in epithelial tumors of thyroid and parathyroid glands, kidney, thymus, and female genital tract. PAX8 is increasingly used in the establishment of tissue of origin in carcinomas and has recently been identified in a subset of small blue round cell tumors including Ewing sarcomas/PNETs. However, it is unclear if this association in ES/PNETs is due to renal origin or is PNET specific. In this study we investigated the PAX8 staining pattern of primary renal and extra-renal ES/PNETs to explore its potential diagnostic and prognostic role. A tissue microarray (TMA) of 22 cases of extra-renal Ewing/PNETs and two separate cases of primary renal PNET whole slide sections were immunohistochemically stained with rabbit polyclonal PAX8 antibody. PAX8 was positive in 2 of 2 primary renal PNETs and in 14 (64 %) cases of the extra renal PNETs. The association between PAX8 immunoreactivity and Ewing/PNET was identified in both primary renal and extra-renal Ewing/PNETs for the first time. Further studies are warranted to verify these findings and to shed light in the tumorigenesis of Ewing/ PNET. However, PAX8 is not useful in establishing a diagnosis of Ewing/PNET due to its presence in different tumors like carcinomas, lymphomas and sarcomas. PAX8 does not seem to have prognostic value.
C1 [Markow, Michael] University of South Florida, College of Medicine, Department of Pathology and Cell Biology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
[Bui, M Marilyn] University of South Florida, College of Medicine, Department of Pathology and Cell Biology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
[Lin, Hui-Yi] Moffitt Cancer Center, Department of BiostatisticsTampa, FL, USA.
[Lloyd, Mark] H. Lee Moffitt Cancer Center and Research Institute, Analytic Microscopy CoreTampa, FL, USA.
[Sexton, J Wade] Moffitt Cancer Center and Research Institute, Department of Genitourinary OncologyTampa, FL, USA.
[Dhillon, Jasreman] University of South Florida, College of Medicine, Department of Pathology and Cell Biology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
RP Dhillon, J (reprint author), University of South Florida, College of Medicine, Department of Pathology and Cell Biology, 33612 Tampa, USA.
EM jasreman.dhillon@moffitt.org
CR Plachov D, Chowdhury K, Walther C, Simon D, Guenet JL, Gruss P, 1990, PAX8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development 110(2): 643–651
Tacha D, Zhou D, Cheng L, 2011, Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol 19(4):293–299
Laury AR, Perets R, Piao H, Krane JF, Barletta JA, French C, Chirieac LR, Lis R, Loda M, Hornick JL, Drapkin R, Hirsch MS, 2011, A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol 35(6):816–826
Koo J, Mertens RB, Mirocha JM,Wang HL, Dhall D, 2012, Value of islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. Mod Pathol 25(6):893–901
Ordonez NG, 2012, Value of PAX8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol 19(3):140–151
Tan PH, Cheng L, Rioux-Leclercq N, Merino MJ, Netto G, Reuter VE, Shen SS, Grignon DJ, Montironi R, Eqevad L, Srigley JR, Delahunt B, Moch H, ISUP Renal Tumor Panel, 2013, ISUP renal tumor panel. Renal tumors: diagnostic and prognostic biomarkers. Am J Surg Pathol 37(10):1518–1531
Chang A, Brimo F, Montgomery EA, Epstein JI, 2013, Use of PAX8 and GATA3 in diagnosing sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma. Hum Pathol 44(8):1563– 1568
Carney EM, Banerjee P, Ellis CL, Albadine R, Sharma R, Chaux AM, Burger PC, Netto GJ, 2011, PAX2(−)/PAX8(−)/inhibin A(+, immunoprofile in hemangioblastoma: a helpful combination in the differential diagnosis with metastatic clear cell renal cell carcinoma to the central nervous system. Am J Surg Pathol 35(2):262–267
Doyle LA, Fletcher CD, 2014, Peripheral hemangioblastoma: clinicopathologic characterization in a series of 22 cases. Am J Surg Pathol 38(1):119–127
Fan R, 2014, PAX immunoreactivity in poorly differentiated small round cell tumors of childhood. Fetal Pediatr Pathol 33(4):244–252
Zhao M,Williamson SR, Yu J, XiaW, Li C, Zheng J, ZhuY, Sun K, Wang Z, Cheng L, 2013, PAX8 expression in sporadic hemangioblastoma of the kidney supports a primary renal cell lineage: implications for differential diagnosis. Hum Pathol 44(10): 2247–2255
Surdez D, Benetkiewicz M, Perrin V, Han ZY, Pierron G, Ballet S, Lamoureux F, Redini F, Decouvelaere AV, Daudigeos-Dubus E, Geoerger B, de Pinieux G, Delattre O, Tirode F, 2012, Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes Ewing sarcoma growth. Cancer Res 72(17):4494–4503
Holmes BJ, Gown AM, Vang R, Ronnett BM, Yemelyanova A, 2014, PAX8 expression in uterine malignant mesodermal mixed tumor, carcinosarcoma). Int J Gynecol Pathol 33(4):42–31
Sangoi AR, Cassarino DS, 2013, PAX-8 expression in primary and metastatic Merkel cell carcinoma: an immunohistochemical analysis. Am J Dermatopathol 35(4):448–451
Morgan EA, Pozdnyakova O, Nascimento AF, Hirsch MS, 2013, PAX8 and PAX5 are differentially expressed in B-cell and T-cell lymphomas. Histopathology 62(3):406–413
Fletcher CD, Bridge JA, Hogendoorn P, Mertens F, 2013, WHO classification of tumours of soft tissue and bone. Fourth Edition. World Health Organization; 468 pp.
BuiMM, Han G, Geza A, Reed D, Gonzalez R, Pasha TL, Zhang P, 2011, Connexin 43 is a prognostic biomarker for Ewing Sarcoma, EWS)/primitive neuroectodermal tumor, PNET). Sarcoma 2011: 971050
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 115
EP 120
DI 10.1007/s12253-015-9986-8
PG 6
ER
PT J
AU Li, H
Jiang, Y
Pei, F
Li, L
Yan, B
Geng, X
Liu, B
AF Li, Hui
Jiang, Yang
Pei, Fenghua
Li, Lu
Yan, Bingzhu
Geng, Xinyu
Liu, Bingrong
TI Aldehyde Dehydragenase 1 and Nodal as Significant Prognostic Markers in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALDH1; Nodal; Colorectal cancer; Predictive factors
ID ALDH1; Nodal; Colorectal cancer; Predictive factors
AB This study aimed to analyze prognostic significance of aldehyde dehydragenase 1 (ALDH1) and Nodal expression in patients with colorectal cancer. ALDH1 and Nodal expressions were observed based on the immunohistochemistry staining from 108 colorectal cancer patients. Scores were given to the staining intensity and percentage of positive cells, and sum of two scores for each case was used to define the groups of ALDH1 and Nodal.We also investigated the protein and mRNA levels of ALDH1 and Nodal by Western blot and qRT-PCR assays. The results were analyzed with the clinicopathologic parameters of these patients. The results indicated that expressions of ALDH1 and Nodal were significantly correlated with the differentiation degree, metastasis, number of tumor positive lymph nodes and AJCC stage. ALDH1 was inclined to express more in the worse differentiated degrees, lymph node metastasis, and worse AJCC stage of colorectal cancer patients. And the expression of Nodal was inversely compared with ALDH1.While the expression of ALDH1 was inversely correlated with the Nodal (r = −0.709, P < 0.01).
C1 [Li, Hui] The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, Xuefu Road 246, Nangang District, 150001 Harbin, Heilongjiang, China.
[Jiang, Yang] Harbin Medical University, Department of Pathology, Xuefu Road 157, 150081 Harbin, Heilongjiang, China.
[Pei, Fenghua] The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, Xuefu Road 246, Nangang District, 150001 Harbin, Heilongjiang, China.
[Li, Lu] The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, Xuefu Road 246, Nangang District, 150001 Harbin, Heilongjiang, China.
[Yan, Bingzhu] The Second Affiliated Hospital of Harbin Medical University, Department of Infectious Disease, Xuefu Road 246, 150001 Harbin, Heilongjiang, China.
[Geng, Xinyu] The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, Xuefu Road 246, Nangang District, 150001 Harbin, Heilongjiang, China.
[Liu, Bingrong] The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, Xuefu Road 246, Nangang District, 150001 Harbin, Heilongjiang, China.
RP Liu, B (reprint author), The Second Affiliated Hospital of Harbin Medical University, Department of Gastroenterology, 150001 Harbin, China.
EM bingrongliu1963@126.com
CR Saika K, Sobue T, 2013, Cancer statistics in the world. Gan to Kagaku ryoho 40:2475–2480
Giuliani F, De Vita F, Colucci G, Pisconti S, 2010, Maintenance therapy in colon cancer. Cancer Treat Rev 36(Suppl 3):S42–S45
Hess DA,Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, EadesWC, Creer MH, Nolta JA, 2006, Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood 107:2162– 2169
Dave B, Chang J, 2009, Treatment resistance in stem cells and breast cancer. J Mammary Gland Biol Neoplasia 14:79–82
Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, Wang H, Liu Z, Su Y, Stass SA, Katz RL, 2009, Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 7:330–338
Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z, Stass SA, Jiang F, 2010, ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Investig 90: 234–244
Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM, 2009, ALDH1 is a marker for normal and malignant human colonic stem cells and track SC overpolution during cancer tumorigenesis. Cancer Res 69:3382– 3389
Schier AF, Shen MM, 2000, Nodal signalling in vertebrate development. Nature 403:385–389
Strizzi L, HardyKM, Kirschmann DA, Ahrlund-Richter L, Hendrix MJ, 2012, Nodal expression and detection in cancer: experience and challenges. Cancer Res 72:1915–1920
Hamilton SR, Vogelstein B,Kudo S, Nakamura S, Hainaut P, Rubio AC, Sobin LH, Fogt F, Winawer SJ, Goldgar DE, Jass JR, 2000, Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA, eds, World Health Organization Classification of Tumors, International Agency for Research on Cancer, IARC). Press, Lyon, pp. 110–111
Li FY, Lai MD, 2009, Colorectal cancer, one entity or three. J Zhejiang Univ Sci B 10:219–229
Ma I, AllanAL, 2011, The role of human aldehyde dehydrogenases in normal and cancer stem cells. Stem Cell Rev 7:292–306
Yasmeen R, Jeyakumar SM, Reichert B, Yang F, Ziouzenkova O, 2012, The contribution of vitamin a to autocrine regulation of fat depots. Biochim Biophys Acta 1821:190–197
Goossens-Beumer IJ, Zeestraten EC, Benard A, Christen T, Reimers MS, Keijzer R, Sier CF, Liefers GJ, Morreau H, Putter H, Vahrmeijer AL, van de Velde CJ, Kuppen PJ, 2014, Clinical prognostic value of combined analysis of Aldh1, survivin, and EpCAM expression in colorectal cancer. Br J Cancer 110:2935–2944
Fitzgerald TL, Rangan S, Dobbs L, Starr S, Sigounas G, 2014, The impact of aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer. J Surg Res 192:82–89
Oh SY, Sohn SH, Yim H, Lee D, SuhKW, KimYB, 2015, ALDH1 is a prognostic factor for patients treated with neoadjuvant chemoradiotherapy and radical resection for stage III rectal cancer. J Surg Oncol 111:243–247
Zhou F, Mu YD, Liang J, Liu ZX, Zhou D, NingWL, Li YZ, Ding D, Zhang JF, 2015, Aldehyde dehydrogenase 1: a specific cancer stemcellmarker for human colorectal carcinoma.MolMed Rep 11: 3894–3899
Hou Y, Liu YY, Zhao XK, 2013, Expression of aldehyde dehydrogenase 1 in colon cancer. Asian Pac J Trop Med 6:574–577
Juan H, Hamada H, 2001, Roles of nodal-lefty regulatory loops in embryonic pattering of vertebrates. Genes Cells 6:923–930
Zarzynska JM, 2014, Two faces of TGF-beta1 in breast cancer. Mediat Inflamm 2014:141747
Xu G, Zhong Y, Munir S, Yang BB, Tsang BK, Peng C, 2004, Nodal induces apoptosis and inhibits proliferation in human epithelial ovarian cancer cells via activin receptor-like kinase 7. J Clin Endocrinol Metab 89:5523–5534
Zhong Y, Xu G, Ye G, Lee D, Modica-Amore J, Peng C, 2009, Nodal and activin receptor-like kinase 7 induce apoptosis in human breast cancer cell lines: role of caspase 3. Int J Physiol Pathophysiol Pharmacol 1:83–96
De Silva T, Ye G, Liang YY, Fu G, Xu G, Peng C, 2012, Nodal promotes glioblastoma cell growth. Front Endocrinol, Lausanne, 3:59
GongY, GuoY, Hai Y, YangH, LiuY, YangS,ZhangZ,MaM,Liu L, Li Z, He Z, 2014, Nodal promotes the self-renewal of human colon cancer stem cells via an autocrine manner through Smad2/ 3signaling pathway. Biomed Res Int 2014:364134
Katsuno Y, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, MiyazonoK(2012, Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-b. J Pathol 228:391–404
Wang Y, Jiang Y, Tian T, Hori Y, Wada N, Ikeda J, Morii E, 2013, Inhibitory effect of nodal on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma of uterus. Biochem Biophys Res Commun 440:731–736
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 121
EP 127
DI 10.1007/s12253-015-9984-x
PG 7
ER
PT J
AU Xu, H
Seifert, PR
Niu, X
Li, Y
Bui, MM
AF Xu, Hairong
Seifert, P Robert
Niu, Xiaohui
Li, Yuan
Bui, M Marilyn
TI The Establishment and Utility of a Free Online Database of Primary Bone Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Online database; Bone tumors; Establishment; Epidemiology; Tool
ID Online database; Bone tumors; Establishment; Epidemiology; Tool
AB Primary bone tumors are rare. It is estimated that 3010 individuals (1680 male and 1330 female) were diagnosed with malignancies of bone and joints in 2013 in the United States. [1] The yearly incidence is about 0.9 per 100,000. In comparison, the 2013 incidence of prostate and breast cancer was estimated to be 238,590 and 234,580 respectively. [1] The rarity of this entity together with the non-specific clinical symptoms and complex imaging findings, make this a challenging diagnosis for clinicians. [2–4] However, early and accurate diagnosis is the key to appropriate treatment and better clinical outcome. Primary bone tumors follow a somewhat rigid age-specific distribution. [5, 6] For instance, between the ages of 10– 20 years, there is an incidence peak for osteochondroma and osteosarcoma. [7] Beyond age 40 years, there is a steady increase in chondrosarcoma, myeloma and lymphoma. [7] The use of epidemiological data, including the patient’s age, sex and tumor location, has been the standard 1st approach to establishing a differential diagnosis. This information is augmented by radiological and histological studies to render an accurate diagnosis. However, in many instances, comprehensive epidemiology data can indicate a definite diagnosis before obtaining diagnostic tissue via an invasive procedure. [8, 9] Although epidemiological information on bone and soft tissue tumors can be gathered from literature searches and published sources, an online source would provide greater convenience. In addition, a patient database could provide a real-time and up-to-date source unlike literature and textbook searches. [10–13] To the best of our knowledge, based on Chinese and English literature searches, no such database has so far been described. A database is defined as a data structure composed of organized and interrelated data. They are designed to facilitate the collection of data and support the acquisition of relevant information. [14] Here, we describe our recently built, free, online database of primary bone tumors, including its construction and the main practical utility. This may serve as a reference for users interested in constructing a free online database. It will also be useful for sarcoma physicians and researchers alike.
C1 [Xu, Hairong] Peking University, Beijing Ji Shui Tan Hospital, Department of Orthopedic Oncology SurgeryBeijing, China.
[Seifert, P Robert] University of South Florida, College of Medicine, Department of Pathology and Cell BiologyTampa, FL, USA.
[Niu, Xiaohui] Peking University, Beijing Ji Shui Tan Hospital, Department of Orthopedic Oncology SurgeryBeijing, China.
[Li, Yuan] Peking University, Beijing Ji Shui Tan Hospital, Department of Orthopedic Oncology SurgeryBeijing, China.
[Bui, M Marilyn] University of South Florida, College of Medicine, Department of Pathology and Cell BiologyTampa, FL, USA.
RP Bui, MM (reprint author), University of South Florida, College of Medicine, Department of Pathology and Cell Biology, Tampa, USA.
EM Marilyn.Bui@moffitt.org
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics, 2013. CA Cancer J Clin 63:11–30
Franchi A, 2012, Epidemiology and classification of bone tumors. Clin Cases Miner Bone Metab 9:92–95
Limb D, Dreghorn C, Murphy JK, Mannion R, 1994, Primary lymphoma of bone. Int Orthop 18:180–183
Widhe B,Widhe T, 2000, Initial Symptoms and Clinical Features in Osteosarcoma and Ewing Sarcoma*. J Bone Joint Surg Am 82:667
Campanacci M, 1999, Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. Springer Verlag, Wien
Unni KK, Inwards CY, 2010, Dahlin's bone tumors: general aspects and data on 10,165 cases. Lippincott Williams & Wilkins, Philadelphia
Anfinsen KP, Devesa SS, Bray F, et al., 2011, Age-period-cohort analysis of primary bone cancer incidence rates in the United States, 1976–2005). Cancer Epidemiol Biomark Prev 20:1770–1777
Wu JS and Hochman M. Bone Tumors: A Practical Guide to Imaging. Springer: New York, 2012, p.414.
Davies AM, Sundaram M, James SJ, 2009, Imaging of bone tumors and tumor-like lesions: techniques and applications. Springer, New York, p 716
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Fletcher CD, Unni KK, Mertens F, 2002, Pathology & genetics: tumours of soft tissue and bone. World Health Organization, Geneva
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Iarc.Who Classification of Tumours of Soft Tissue and BoneIARC WHO Classification of Tumours SeriesVolume 5 of World Health Organization Classification of Tumours. 4 ed.: World Health Organization: Geneva, 2013, p.427
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Niu XH, Xu HR, Inwards CY, Li Y, Zhang Q, Ding Y, Letson GD, BuiMM(2015, Primary bone tumors: epidemiological comparison of 9,200 patients treated at Beijing Ji Shui Tan Hospital, Beijing, China with 10, 165 patients at Mayo Clinic, Rochester, MN, USA. Arch Pathol Lab Med 139(9):1149–1155
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Frain B, 2012, Responsive web design with HTML5 and CSS3. Packt Publishing, UK
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 129
EP 133
DI 10.1007/s12253-015-9982-z
PG 5
ER
PT J
AU Bienkiewicz, J
Smolarz, B
Malinowski, A
AF Bienkiewicz, Jan
Smolarz, Beata
Malinowski, Andrzej
TI Association Between Single Nucleotide Polymorphism +276G > T (rs1501299) in ADIPOQ and Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Single nucleotide polymorphism; + 276G>T; Obesity; Adiponectin; ADIPOQ
ID Endometrial cancer; Single nucleotide polymorphism; + 276G>T; Obesity; Adiponectin; ADIPOQ
AB Current literature gives evidence of an indisputable role adiponectin plays in adipose tissue metabolism and obesity-related diseases. Moreover, latest research efforts focus on linking genetic markers of this adipocytokine’s gene (ADIPOQ) with cancer. Aim of this study was to determine the genotype distribution of single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQ and an attempt to identify the impact this polymorphism exerts on endometrial cancer risk in obese females. The test group comprised 90 women treated surgically for endometrial cancer between 2000 and 2012 in the Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Polish Mothers’ Memorial Hospital - Research Institute, Lodz, Poland. 90 individuals treated in the parallel period for uterine fibroids constituted the control group. Patients within both groups were stratified according to BMI into: lean, overweight and obese subjects. Statistical analysis was performed between two major groups and, furthermore, within the abovementioned subgroups. The analysis revealed that allele G of the investigated polymorphism in obese women with endometrial cancer is significantly more frequent, and allele T is significantly less frequent than in lean controls. However, no significant correlation was observed between the polymorphism and endometrial cancer in lean and overweight females. Single nucleotide polymorphism +276G > T (rs1501299) in ADIPOQmay be considered to be a risk factor of endometrial cancer. Further research on SNP in EC is warranted to obtain more conclusive outcomes.
C1 [Bienkiewicz, Jan] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
[Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular GeneticsLodz, Poland.
[Malinowski, Andrzej] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
RP Bienkiewicz, J (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Lodz, Poland.
EM jan.a.bienkiewicz@gmail.com
CR Siegel R, Naishadham D, Jemal A, et al., 2012, Cancer statistics. CA Cancer J Clin 62(1):10–29
Bokhman JV, 1983, Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15(1):10–17
Crosbie EJ, Zwahlen M, Kitchener HC, et al., 2010, Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 19(12):3119–3130
Bhaskaran K, Douglas I, Forbes H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet. 2014 Aug 30;384(9945):755–765.
SGO Clinical Practice Endometrial Cancer Working Group, Burke WM, Orr J, et al., 2014, Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol 134(2):385–392
Calle EE, Rodriguez C, Walker-Thurmond K, et al., 2003, Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638
Friberg E, Mantzoros CS, Wolk A, 2007, Diabetes and risk of endometrial cancer: a population-based prospective cohort study. Cancer Epidemiol Biomark Prev 16(2):276–280
Hecht J, Mutter GL, 2006, Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 24(29):4783–4791
Tilg H, 2006)Moschen AR adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783
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Fisman EZ, Tenenbaum A, 2014, Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary Disease? Cardiovasc Diabetol 13:103
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Gu HF, 2009, Biomarkers of adiponectin: plasma protein variation and genomic DNA polymorphisms. Biomark Insights 4:123–133
Melistas L, Mantzoros CS, Kontogianni M, et al., 2009, Association of the +45 T > G and +276G > T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 161(6):845–852
Stumvoll M, Tschritter O, Fritsche A, et al., 2002, Association of the T-G polymorphism in adiponectin, exon 2, with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51(1):37–41
Chu H, Wang M, Zhong D, et al., 2013, AdipoQ polymorphisms are associated with type 2 diabetes mellitus: a meta-analysis study. Diabetes Metab Res Rev 29(7):532–545
Teras LR, Goodman M, Patel AV, et al., 2009, No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. Cancer Epidemiol Biomark Prev 18(9):2553–2557
Ye C,Wang J, Tan, et al., 2013)Meta-analysis of adiponectin polymorphisms and colorectal cancer risk. Int J Med Sci 10(9):1113– 1120
Dhillon PK, Penney KL, Schumacher F, et al., 2011, Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer. Cancer Epidemiol Biomark Prev 20(12):2618–2627
Chen X, Xiang YB, Long JR, et al., 2012, Genetic polymorphisms in obesity-related genes and endometrial cancer risk. Cancer 118(13):3356–3364
Meyer LA, Westin SN, Lu KH, et al., 2008, Genetic polymorphisms and endometrial cancer risk. Expert Rev Anticancer Ther 8(7):1159–1167
Fan HJ, Wen ZF, Xu BL, et al., 2013, Three adiponectin rs1501299G/T, rs822395A/C, and rs822396A/G polymorphisms and risk of cancer development: a meta-analysis. Tumour Biol 34(2):769–778
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 135
EP 138
DI 10.1007/s12253-015-9985-9
PG 4
ER
PT J
AU Fekete, F
Fadgyas, B
Papp,
Szilagyi,
Prohaszka, Z
Muller, B
Kovacs, G
AF Fekete, Ferenc
Fadgyas, Balazs
Papp, Eva
Szilagyi, Agnes
Prohaszka, Zoltan
Muller, Brigitta
Kovacs, Gabor
TI The role of mannose binding lectin on fever episodes in pediatric oncology patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MBL; Polymorphism; Febrile neutropenia; Oncohematology
ID MBL; Polymorphism; Febrile neutropenia; Oncohematology
AB Despite significant changes in pediatric oncological therapy, mortality is still high, mainly due to infections. Complement system as an ancient immune defense against microorganisms plays a significant role in surmounting infections, therefore, deficiency of its components may have particular importance in malignancies. The present paper assesses the effect of promoter (X/Y) and exon 1 (A/0) polymorphisms of the MBL2 gene altering mannose binding lectin (MBL) serum level in pediatric oncological patients with febrile neutropenia. Furthermore, frequency distribution of MBL2 alleles in children with malignancies and age-matched controls was analysed. Fifty-four oncohematological patients and 53 children who had undergone pediatric surgery were enrolled into this retrospective study. No significant differences were found in the frequency of MBL2 alleles between the hematooncologic and control group. The average duration of fever episodes was significantly shorter (p = 0.035) in patients carrying genotypes (AY/AY and AY/AX) that encode normal MBL level, compared to individuals with genotypes associated with lower functional MBL level (AX/AX, AY/0, AX/0, or 0/0) (days, median (IQ range) 3.7(0–5.4) vs. 5.0(3.8–6.6), respectively). In conclusion, our data suggest that MBL2 genotypes may influence the course of febrile neutropenia in pediatric patients with malignancies, and may contribute to clarification of the importance of MBL in infections.
C1 [Fekete, Ferenc] Heim Pal Children's Hospital, Department of Hematology, Madarasz Street Building, Madarasz utca 22-24, 1131 Budapest, Hungary.
[Fadgyas, Balazs] Heim Pal Children’s Hospital, Department of Pediatric Surgery and TraumatologyBudapest, Hungary.
[Papp, Eva] Gyula Nyiro Hospital, National Institute of Psychiatry and AddictionsBudapest, Hungary.
[Szilagyi, Agnes] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Prohaszka, Zoltan] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Muller, Brigitta] Heim Pal Children's Hospital, Department of Hematology, Madarasz Street Building, Madarasz utca 22-24, 1131 Budapest, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
RP Fekete, F (reprint author), Heim Pal Children's Hospital, Department of Hematology, 1131 Budapest, Hungary.
EM efekete@heimpalkorhaz.hu
CR Walport MJ, 2001, Complement Second of two parts. N Engl J Med 344:1140–1144
Walport MJ, 2001, Complement First of two parts. N Engl J Med 344:1058–1066
Neth O, Jack DL, Dodds AW, et al., 2000, Mannose-binding lectin binds to a range of clinically relevantmicroorganisms and promotes complement deposition. Infect Immun 68:688–693
Garred P, 2008, Mannose-binding lectin genetics: from a to Z. Biochem Soc Trans 36:1461–1466
Garred P, Larsen F, Madsen HO, et al., 2003, Mannose-binding lectin deficiency–revisited. Mol Immunol 40:73–84
Bouwman, LH, Roep, BO & Roos,, 2006, A Mannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol. 67:247–256.
Ruskamp JM, Hoekstra MO, Rovers MM, et al., 2006,, 2006, mannose-binding lectin and upper respiratory tract infections in children and adolescents: a review. Arch Otolaryngol Head Neck Surg 132:482–486
Koutsounaki E, Goulielmos GN, Koulentaki M, et al., 2008, Mannose-binding lectin MBL2 gene polymorphisms and outcome of hepatitis C virus-infected patients. J Clin Immunol 28:495–500
Garred P, S J,J, Quist L, et al, 2003, Association of mannosebinding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 188:1394–1403
Schmiegelow K, Garred P, Lausen B, et al., 2002, Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia. Blood 100:3757–3760
Neth O, Hann I, Turner MW, et al., 2001, Deficiency of mannosebinding lectin and burden of infection in children with malignancy: a prospective study. Lancet 358:614–618
Ghazi M, Isadyar M, Gachkar L, et al., 2012, Serum levels of mannose-binding lectin and the risk of infection in pediatric oncology patients with chemotherapy. J Pediatr Hematol Oncol 34:128– 130
Horiuchi T, Gondo H, Miyagawa H, et al., 2005, Association of MBL gene polymorphismswithmajor bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT. Genes Immun 6:162–166
Peterslund NA, Koch C, Jensenius JC, et al., 2001, Association between deficiency ofmannose-binding lectin and severe infections after chemotherapy. Lancet 358:637–638
Vekemans M, Robinson J, Georgala A, et al., 2007, Low mannosebinding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy. Clin Infect Dis 44:1593–1601
Frakking FN, Brouwer N, Dolman KM, et al., 2011, Mannosebinding lectin, MBL, as prognostic factor in paediatric oncology patients. Clin Exp Immunol 165:51–59
Bergmann OJ, Christiansen M, Laursen I, et al., 2003, Low levels of mannose-binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy. Eur J Haematol 70:91–97
Lausen B, Schmiegelow K, Andreassen B, et al., 2006, Infections during induction therapy of childhood acute lymphoblastic leukemia– no association to mannose-binding lectin deficiency. Eur J Haematol 76:481–487
Martinez-Lopez J, Rivero A, Rapado I, et al., 2009, Influence of MBL-2 mutations in the infection risk of patients with follicular lymphoma treated with rituximab, fludarabine, and cyclophosphamide. Leuk Lymphoma 50:1283–1289
Rubnitz JE, Howard SC, Willis J, et al., 2008, Baseline mannose binding lectin levels may not predict infection among children with leukemia. Pediatr Blood Cancer 50:866–868
Zehnder, A, Fisch, U, Hirt, A, et al., 2009, prognosis in pediatric hematologic malignancies is associated with serum concentration of mannose-binding lectin-associated serine protease-2, MASP-2). Pediatr Blood Cancer. 2009;53: 53–57.
Frakking FN, Israels J, Kremer LC, et al., 2011, Mannose-binding lectin, MBL, and the risk for febrile neutropenia and infection in pediatric oncology patients with chemotherapy. Pediatr Blood Cancer 57:89–96
Bang P, Laursen I, Thornberg K, et al., 2008,, 2008, the pharmacokinetic profile of plasma-derived mannan-binding lectin in healthy adult volunteers and patients with Staphylococcus aureus septicaemia. Scand J Infect Dis 40: 44–48
Frakking FN, Brouwer N, van de Wetering MD, et al., 2009, Safety and pharmacokinetics of plasma-derived mannose-binding lectin, MBL, substitution in children with chemotherapy-induced neutropaenia. Eur J Cancer 45:505–512
Valdimarsson H, 2003, Infusion of plasma-derived mannan-binding lectin, MBL, into MBL-deficient humans. Biochem Soc Trans 31:768–769
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 139
EP 143
DI 10.1007/s12253-015-9992-x
PG 5
ER
PT J
AU Jamdade, SV
Mundhe, AN
Kumar, P
Tadla, V
Lahkar, M
AF Jamdade, Sudhir Vinayak
Mundhe, A Nitin
Kumar, Parveen
Tadla, Venkatesh
Lahkar, Mangala
TI Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cisplatin; Raloxifene; Nephrotoxicity; Inflammation; Pro-inflammatory cytokines
ID Cisplatin; Raloxifene; Nephrotoxicity; Inflammation; Pro-inflammatory cytokines
AB Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumours like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its antitumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFκB). Moreover, assessment of tumour reduction was done by measuring tumour volume and percentage tumour reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-α and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-α and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumour reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumour activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity.
C1 [Jamdade, Sudhir Vinayak] Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, Assam, India.
[Mundhe, A Nitin] Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, Assam, India.
[Kumar, Parveen] Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, Assam, India.
[Tadla, Venkatesh] Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, Assam, India.
[Lahkar, Mangala] Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, Assam, India.
RP Jamdade, SV (reprint author), Gauhati Medical College, National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacology and Toxicology, Laboratory of Molecular Pharmacology and Toxicology, 781032 Guwahati, India.
EM vinayak757@gmail.com
CR Bogdanovic G, Kojic V, Srdic T, Jakimov D, Djuran MI, Bugarcic ZD, Baltic M, Baltic VV, 2002, Growth effects of some platinum(II, complexes with sulfur-containing carrier ligands on MCF7 human breast cancer cell line upon simultaneous administration with taxol. Met Based Drugs 9:33–43
Aisner J, Jacobs M, Sinabaldi V, Gray W, Eisenberger M, 1994, Chemoradiotherapy for the treatment of regionally advanced head and neck cancers. Semin Oncol 21:35–44
Kelland L, 2007, The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584
Ali BH, Al Moundhri MS, 2006, Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol 44:1173–1183
Ramesh G, Kimball SR, Jefferson LS, Reeves WB, 2007, Endotoxin and cisplatin synergistically stimulate TNF-alpha production by renal epithelial cells. Am J Physiol Renal Physiol 292: F812–F819
Basnakian AG, Apostolov EO, Yin X, Napirei M, Mannherz HG, Shah SV, 2005, Cisplatin nephrotoxicity is mediated by deoxyribonuclease I. J Am Soc Nephrol 16:697–702
Arany I, Safirstein RL, 2003, Cisplatin nephrotoxicity. Semin Nephrol 23:460–464
Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, Oh DJ, Lu L, Klein CL, Dinarello CA, Edelstein CL, 2007, Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin, IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther 322:8– 15
Ramesh G, Brian Reeves W, 2006, Cisplatin increases TNF-alpha mRNA stability in kidney proximal tubule cells. Ren Fail 28:583– 592
Yao X, Panichpisal K, Kurtzman N, Nugent K, 2007, Cisplatin nephrotoxicity: a review. Am J Med Sci 334:115–124
Ramesh G, ReevesWB(2002, TNF-alphamediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 110:835–842
Ramesh G, Reeves WB, 2003, TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. Am J Physiol Renal Physiol 285:F610–F618
Ramesh G, ReevesWB, 2004, Salicylate reduces cisplatin nephrotoxicity by inhibition of tumour necrosis factor-alpha. Kidney Int 65:490–499
Dong Z, Atherton SS, 2007, Tumour necrosis factor-alpha in cisplatin nephrotoxicity: a homebred foe? Kidney Int 72:5–7
Kaya H, Ozkaya O, SezikM, Arslanoglu E,Yilmaztepe A, Ulukaya E, 2005, Effects of raloxifene on serum malondialdehyde, erythrocyte superoxide dismutase, and erythrocyte glutathione peroxidase levels in healthy postmenopausal women. Maturitas 50:182–188
Lippuner K, Buchard PA, De Geyter C, Imthurn B, Lamy O, Litschgi M, Luzuy F, Schiessl K, Stute P, Birkhauser M, 2012, Recommendations for raloxifene use in daily clinical practice in the Swiss setting. Eur Spine J 21:2407–2417
Shibata MA, Morimoto J, Shibata E, Kurose H, Akamatsu K, Li ZL, Kusakabe M, Ohmichi M, Otsuki Y, 2010, Raloxifene inhibits tumour growth and lymph node metastasis in a xenograft model of metastatic mammary cancer. BMC Cancer 10:566
Galien R, Garcia T, 1997, Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-kappaB site. Nucleic Acids Res 25:2424–2429
Olivier S, Close P, Castermans E, de Leval L, Tabruyn S, Chariot A, Malaise M, Merville MP, Bours V, Franchimont N, 2006, Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature. Mol Pharmacol 69:1615–1623
K.K. Thakur, N.B. Bolshette, C. Trandafir, V.S. Jamdade, A. Istrate, R. Gogoi, A. Cucuianu, Role of toll-like receptors in multiple myeloma and recent advances. Exp Hematol, 2014, 43(3):158–167
Kumar P, Bolshette NB, Jamdade VS, Mundhe NA, Thakur KK, Saikia KK, LahkarM(2013, Breast cancer status in India: an overview. J Carcinog 3:177–183
Cheung J, Mak YT, Papaioannou S, Evans BA, Fogelman I, Hampson G, 2003, Interleukin-6, IL-6), IL-1, receptor activator of nuclear factor kappaB ligand, RANKL, and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene. J Endocrinol 177:423–433
Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Hewitt SM, Miyaji T, McLeroy P, Nibhanupudy B, Li S, Star RA, 2001, Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 60:2118–2128
Kalaitzidis D, Gilmore TD, 2005, Transcription factor cross-talk: the estrogen receptor and NF-kappaB. Trends Endocrinol Metab 16:46–52
Kumar P, Kadakol A, Shasthrula P, Mundhe NA, Jamdade VS, Barua CC, Gaikwad AB, 2015, Curcumin as an adjuvant to breast cancer treatment. Anti Cancer Agents Med Chem 15:647–656
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Liu Y, Webb HK, Fukushima H, Micheli J, Markova S, Olson JL, Kroetz DL, 2012, Attenuation of cisplatin-induced renal injury by inhibition of soluble epoxide hydrolase involves nuclear factor kappaB signaling. J Pharmacol Exp Ther 341:725–734
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB, 2010, Mechanisms of cisplatin nephrotoxicity. Toxins, Basel, 2:2490– 2518
Schrier RW, 2002, Cancer therapy and renal injury. J Clin Invest 110:743–745
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 145
EP 153
DI 10.1007/s12253-015-9988-6
PG 9
ER
PT J
AU Hutoczki, G
Bognar, L
Toth, J
Scholtz, B
Zahuczky, G
Hanzely, Z
Csosz,
Remenyi-Puskar, J
Kallo, G
Hortobagyi, T
Klekner,
AF Hutoczki, Gabor
Bognar, Laszlo
Toth, Judit
Scholtz, Beata
Zahuczky, Gabor
Hanzely, Zoltan
Csosz, Eva
Remenyi-Puskar, Judit
Kallo, Gergo
Hortobagyi, Tibor
Klekner, Almos
TI Effect of Concomitant Radiochemotherapy on Invasion Potential of Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radiochemotherapy; Temozolomide; Extracellular matrix; Invasion; Glioblastoma
ID Radiochemotherapy; Temozolomide; Extracellular matrix; Invasion; Glioblastoma
AB Glioblastoma (GBM) is the most common primary brain tumor in adults with inevitable recurrence after oncotherapy. The insufficient effect of "gold standard" temozolomide-based concomitant radiochemotherapy may be due to the inability to prevent tumor cell invasion. Peritumoral infiltration depends mainly on the interaction between extracellular matrix (ECM) components and cell membrane receptors. Changes in invasive behaviour after oncotherapy can be evaluated at the molecular level by determining the RNA expression and protein levels of the invasionrelated ECM components. The expression of nineteen ECM molecules was determined at both RNA and protein levels in thirty-one GBM samples. Fifteen GBM samples originated from the first surgical procedure on patients before oncotherapy, and sixteen GBM samples were collected at the second surgery due to local recurrence after concomitant chemoirradiation. RNA expressions were measured with qRTPCR, and protein levels were determined by quantitative analysis of Western blots. Only MMP-9 RNA transcript level was reduced (p < 0.05) whereas at protein level, eight molecules showed changes concordant with RNA expression with significant decrease in brevican only. The results suggest that concomitant radiochemotherapy does not have sufficient impact on the expression of invasion-related ECM components of glioblastoma, oncotherapy does not significantly affect its invasive behavior. To avoid the spread of tumors into the brain parenchyma, supplementation of antiproliferative treatment with anti-invasive agents may be worth consideration in oncotherapy for glioblastoma.
C1 [Hutoczki, Gabor] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Bognar, Laszlo] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Toth, Judit] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Scholtz, Beata] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Zahuczky, Gabor] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hanzely, Zoltan] National Institute of Clinical Neurosciences, Amerikai ut 57, 1145 Budapest, Hungary.
[Csosz, Eva] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Remenyi-Puskar, Judit] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kallo, Gergo] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hortobagyi, Tibor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Klekner, Almos] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Bognar, L (reprint author), University of Debrecen, Clinical Center, Department of Neurosurgery, 4032 Debrecen, Hungary.
EM neurosurgery.debrecen@freemail.hu
CR Murnyak B, Csonka T, Hegyi K, Mehes G, Klekner A, Hortobagyi T, 2013, Occurrence and molecular pathology of high grade gliomas., in Hungarian). Ideggyogy Sz 66:312–321
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 155
EP 160
DI 10.1007/s12253-015-9989-5
PG 6
ER
PT J
AU Tian, L
Shan, W
Zhang, Y
Lv, X
Li, X
Wei, C
AF Tian, Lei
Shan, Weiyu
Zhang, Yufei
Lv, Xuejun
Li, Xuehua
Wei, Caiyun
TI Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; miR-21; Prognosis
ID Lung cancer; miR-21; Prognosis
AB MicroRNAs (miRNAs) are endogenous small (19– 24 nt long) noncoding RNAs that regulate gene expression in a sequence specific manner. An increasing association between miRNA and cancer has been recently reported. Lung cancer is globally responsible for 1.4 million deaths annually and is the leading cause of cancer-related deaths in both women and men. In this study, we investigated the miR-21 expression in non-small cell lung cancer (NSCLC) to evaluate their value in prognosis of this tumor. Here, we assess miR-21 expression in NSCLC and its clinical significance including survival analysis. The expression of miR-21 in matched normal and tumor tissues of NSCLC was evaluated using a quantitative real-time RT-PCR. A Kaplan–Meier survival curve was generated following a logrank test. It was observed that miR-21 expression was up-regulated in NSCLC tissues compared with noncancerous lung tissues (mean ± SD: 6.7 ± 2.3 vs. 3.7 ± 1.5, P < 0.001). The up-regulation of miR-21 in NSCLC cancer tissues was also significantly correlated with aggressive clinicopathological features.We found that the patients with high miR-21 expression have a higher tumor grade (P = 0.027) and are in higher risk of lymph node metastasis (P = 0.021). Moreover, the results of Kaplan–Meier analyses showed that NSCLC patients with the high miR-21 expression tend to have shorter overall survival and progression free survival (P < 0.001). The multivariate analysis clearly indicated that the high miR-21 expression in biopsy samples may be considered as an independent prognostic factor in NSCLC for decreased survival (RR 3.88; 95%CI, 2.47–6.11). Our data indicate the potential of miR-21 as a novel prognostic biomarker for NSCLC. Large well-designed studies with diverse populations and functional evaluations are warranted to confirm and extend our findings.
C1 [Tian, Lei] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
[Shan, Weiyu] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
[Zhang, Yufei] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
[Lv, Xuejun] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
[Li, Xuehua] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
[Wei, Caiyun] No.88 Hospital of People’s Republic of China, Department of RespirationGuangzhou, China.
RP Tian, L (reprint author), No.88 Hospital of People’s Republic of China, Department of Respiration, Guangzhou, China.
EM drtianlei@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 161
EP 167
DI 10.1007/s12253-015-9979-7
PG 7
ER
PT J
AU Lim, ChL
Looi, LM
Zakaria, ZSS
Sagap, I
Rose, MI
Chin, SF
Jamal, R
AF Lim, Cheng Lay
Looi, Lee Mee
Zakaria, Zulkifli Syed Syed
Sagap, Ismail
Rose, Mohammed Isa
Chin, Siok-Fong
Jamal, Rahman
TI Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Proteomics; 2D-DIGE; LC-MS/MS; Apolipoprotein A1
ID Colorectal cancer; Proteomics; 2D-DIGE; LC-MS/MS; Apolipoprotein A1
AB Early detection of colorectal cancer (CRC) is vital for the improvement of disease prognosis. However to date there are no blood-based biomarkers sensitive and specific enough for early diagnosis. We analysed the differences in serum protein expression of early stage CRC (Dukes’ A and B) and late stage CRC (Dukes’ C and D) against normal controls using 2D Fluorescence Difference Gel Electrophoresis (2D-DIGE). Analysis of the 2D maps showed that 23 proteins were differentially expressed between groups (p≤0.05) and these proteins were identified with LC-MS/MS. Eight proteins were up-regulated and 2 down-regulated in patients with early CRC, whereas 14 proteins were up-regulated and 4 downregulated in those with late CRC compared to normal controls (p≤0.05). Five proteins, namely apolipoprotein A1 (APOA1), apolipoprotein E (APOE), complement factor H (CFH), galectin-7 (GAL7) and synaptojanin-2 (SYNJ2) were validated using ELISA and only APOA1 and GAL-7 showed consistent findings. Further validation using immunohistochemistry showed negative immunoreactivity for GAL-7 in CRC tissues, suggesting that GAL-7 detected in the serum did not originate from the CRC tumour. APOA1 showed positive immunoreactivity but its expression did not correlate with Dukes’ staging (p=0.314), tumour grading (p=0.880) and lymph node involvement (p=0.108). Differences in APOA1 isoforms and/or conformation between serum and tissue samples as well as tumour heterogeneity may explain for the discrepancies between DIGE and ELISA when compared to immunohistochemistry. Structural and functional studies of APOA1 in future would best describe the role of APOA1 in CRC.
C1 [Lim, Cheng Lay] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras, 56000 Kuala Lumpur, Malaysia.
[Looi, Lee Mee] Taylor’s University, Lakeside Campus, School of Biosciences, Subang JayaSelangor, Malaysia.
[Zakaria, Zulkifli Syed Syed] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras, 56000 Kuala Lumpur, Malaysia.
[Sagap, Ismail] Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of SurgeryKuala Lumpur, Malaysia.
[Rose, Mohammed Isa] Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of PathologyKuala Lumpur, Malaysia.
[Chin, Siok-Fong] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras, 56000 Kuala Lumpur, Malaysia.
[Jamal, Rahman] Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras, 56000 Kuala Lumpur, Malaysia.
RP Jamal, R (reprint author), Universiti Kebangsaan Malaysia, UKM Medical Molecular Biology Institute (UMBI), 56000 Kuala Lumpur, Malaysia.
EM rahmanj@ppukm.ukm.edu.my
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 169
EP 177
DI 10.1007/s12253-015-9991-y
PG 9
ER
PT J
AU Benczik, M
Galamb,
Koiss, R
Kovacs, A
Jaray, B
Szekely, T
Szekerczes, T
Schaff, Zs
Sobel, G
Jeney, Cs
AF Benczik, Marta
Galamb, Adam
Koiss, Robert
Kovacs, Attila
Jaray, Balazs
Szekely, Tamas
Szekerczes, Timea
Schaff, Zsuzsa
Sobel, Gabor
Jeney, Csaba
TI Claudin-1 as a Biomarker of Cervical Cytology and Histology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Biomarker; Claudin-1; Immunocytochemistry
ID Cervical cancer; Biomarker; Claudin-1; Immunocytochemistry
AB Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing. A population of 352 women attending colposcopic referral visits resulting in cervical conisation and a second population of 150 women attending routine gynaecological visits with negative cervical cytology were enrolled in a multi-centre clinical study in Hungary. Cytology and HPV (Genoid Full Spectrum HPV Amplification and Detection System) testing were carried out along with immunocytochemistry for CLDN1, and as a reference, using CINtec p16 Cytology Kit. Three different evaluation protocols were used which assessed immunostaining characteristics with or without cytological readings. High correlation observable between p16INK4a and CLDN1 established CLDN1 as a competing marker in cervical cancer. Concordance of CLDN1 immunostaining of cervical intraepithelial neoplasia 2 and above (CIN2+) positives was 84.0 % (73.8–89.3); concordance of CIN2+ negatives was 69.0 % (59.6–75.8). In conclusion, CLDN1 has similar diagnostic potential as p16INK4a, our results established it as a histological and cytological biomarker with the potential to improve the clinical performance of cervical cytology and histology.
C1 [Benczik, Marta] CellCall Ltd, Roppentyu u. 48, 1134 Budapest, Hungary.
[Galamb, Adam] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
[Koiss, Robert] Del-Pesti Centrumkorhaz, Nagyvarad ter 1, 1097 Budapest, Hungary.
[Kovacs, Attila] CellCall Ltd, Roppentyu u. 48, 1134 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Szekely, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
[Jeney, Csaba] CellCall Ltd, Roppentyu u. 48, 1134 Budapest, Hungary.
RP Jeney, Cs (reprint author), CellCall Ltd, 1134 Budapest, Hungary.
EM csjeney@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 179
EP 188
DI 10.1007/s12253-015-9990-z
PG 10
ER
PT J
AU Giaginis, C
Alexandrou, P
Delladetsima, I
Karavokyros, I
Danas, E
Giagini, A
Patsouris, E
Theocharis, S
AF Giaginis, Constantinos
Alexandrou, Paraskevi
Delladetsima, Ioanna
Karavokyros, Ioannis
Danas, Eugene
Giagini, Athina
Patsouris, Efstratios
Theocharis, Stamatios
TI Clinical Significance of Hu-Antigen Receptor (HuR) and Cyclooxygenase-2 (COX-2) Expression in Human Malignant and Benign Thyroid Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid malignancy; Hu-antigen R; Cyclooxygenase-2; Clinicopathological parameters; Immunohistochemistry
ID Thyroid malignancy; Hu-antigen R; Cyclooxygenase-2; Clinicopathological parameters; Immunohistochemistry
AB Hu-antigen R (HuR) is considered to play a crucial role in tumor formation and growth by binding to mRNAs encoding proteins such as Cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 proteins’ expression in human benign and malignant thyroid lesions. HuR and COX-2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 98 patients with benign (n = 48) and malignant (n = 50) lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity and recurrence risk rate. Enhanced HuR and COX-2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0073 and p = 0.0016, respectively), as well as in papillary carcinomas compared to hyperplastic nodules (p = 0.0039 and p = 0.0009, respectively). Positive associations of both HuR and COX-2 expression with follicular cells’ proliferation rate were also noted (p = 0.0087 and p = 0.0127, respectively). In malignant thyroid lesions, elevated COX-2 expression was significantly associated with female patients’ gender (p = 0.0381) and the presence of lymph node metastases (p = 0.0296). The present data support evidence that both HuR and COX-2 may be involved in the malignant state of thyroid neoplasia and may be utilized in the diagnosis of malignant thyroid tumors.
C1 [Giaginis, Constantinos] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Delladetsima, Ioanna] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Karavokyros, Ioannis] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Danas, Eugene] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Giagini, Athina] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
[Theocharis, Stamatios] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str, GR11527 Goudi, Athens, Greece.
RP Theocharis, S (reprint author), University of Athens, Medical School, First Department of Pathology, GR11527 Goudi, Greece.
EM statheocharis@yahoo.com
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McAllister F, Pineda DM, Jimbo M, et al., 2014, dCK expression correlates with 5-fluorouracil efficacy and HuR cytoplasmic expression in pancreatic cancer: a dual-institutional follow-up with the RTOG 9704 trial. Cancer Biol Ther 15:688–698
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 189
EP 196
DI 10.1007/s12253-015-9997-5
PG 8
ER
PT J
AU Chen, YCh
Fang, WL
Wang, RF
Liu, ChA
Yang, MH
Lo, ShSh
Wu, ChW
Li, FYA
Shyr, YM
Huang, KH
AF Chen, Yun-Chi
Fang, Wen-Liang
Wang, Ruei-Fang
Liu, Chien-An
Yang, Muh-Hwa
Lo, Shu-Shun
Wu, Chew-Wen
Li, Fen-Yau Anna
Shyr, Yi-Ming
Huang, Kuo-Hung
TI Clinicopathological Variation of Lauren Classification in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Gastrecotomy; Lauren’s classification
ID Gastric cancer; Gastrecotomy; Lauren’s classification
AB The investigation of prognostic factor for gastric cancer is still desirable because of dismal prognosis in gastric cancer. Lauren’s classification is currently a useful histological classification. There are few large series evaluating the prognostic significance of Lauren’s classification in gastric cancer. From January 1987 to December 2013, a total of 3071 patients received gastrectomy for gastric cancer. According Lauren’s classification, 1423(46.3 %) patients were intestinal type, 1000 patients (32.6 %) were diffuse type, and 648 patients (21.1 %) were mixed type. The clinicopathological characteristics and prognosis in Lauren’s classification were analyzed in these patients. Our results showed that patients with intestinal type gastric cancer (57.7%) had a better 5-year overall survival than diffuse type (45.6 %) and mixed type (43.4 %, P<0.001). The clinicopathological characteristics showed that gastric cancer patients with intestinal type were older (P<0.001), male predominant (P<0.001), smaller tumor size (P<0.001), distal stomach predominant (P<0.001), relative well differentiated (P<0.001), less advanced Borrmann type (P<0.001), less scirrhous type stromal reaction(P<0.001), less infiltrating type of Ming’s histology type(P<0.001), less tumor invasion depth and less lymphovascular invasion (P<0.001). Multivariate analysis with overall survival as an endpoint showed that age (P=0.005), Borrmann classification (P<0.001), pathological T category (P=0.023), pathological N category (P<0.001) and Lauren’s classification (P=0.003) were significant correlated in gastric cancer. Lauren’s classification is an independent prognostic factor in gastric cancer patient undergoing gastrectomy. Lauren’s classification can serve as a prognostic marker for gastric cancer patient receiving gastrectomy. The clinicopathological appearance and prognosis of mixed type gastric cancer is similar to diffuse type gastric cancer.
C1 [Chen, Yun-Chi] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No.201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Fang, Wen-Liang] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No.201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Wang, Ruei-Fang] Shin Kong Wu Ho-Su Memorial Hospital, Department of Emergency MedicineTaipei, Taiwan, Republic of China.
[Liu, Chien-An] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Yang, Muh-Hwa] National Yang-Ming University, School of Medicine, Institute of Clinical MedicineTaipei, Taiwan, Republic of China.
[Lo, Shu-Shun] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Wu, Chew-Wen] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No.201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Li, Fen-Yau Anna] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Shyr, Yi-Ming] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No.201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Huang, Kuo-Hung] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No.201, Sec. 2, Shipai Rd., Beitou District, 11217 Taipei, Taiwan, Republic of China.
RP Huang, KH (reprint author), Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, 11217 Taipei, Taiwan, Republic of China.
EM khhuang@vghtpe.gov.tw
CR Taiwan Public Health Report 2012, Department of Health, Executive Yuan, R.O.C., Taiwan)
Wu CW, Hsiung CA, Lo SS et al, 2006, Nodal dissection for patients with gastric cancer: a randomized controlled trial. Lancet Oncol 7:309–315
Hartgrink HH, van de Velde CJH, Putter H et al, 2004, Extended lymph-node dissection for gastric cancer: who may benefit? final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 22:2069–2077
Lauren P, 1965, The two histologic main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma, an attempt at a histo-clinicalclassification. Acta Parhol Microb Scan 64:31–49
Qiu MZ, Cai MY, Zhang DS et al, 2013, Clinicopathological characteristics and prognostic analysis of lauren classification in gastric adenocarcinoma in China. J Transl Med 11:58
Berlth F, Bollschweiler E, Drebber U et al, 2014, Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol 20(19):5679–5684
Ming SC, 1977, Gastric carcinoma: a pathological classification. Cancer 39(6):2475–2485
American Joint Committee on Cancer, 2010, AJCC cancer staging manual, 7th edn. Springer, New York
Komatsu S, Ichikawa D, Miyamae M et al, 2015, Histological mixed-type as an independent prognostic factor in stage I gastric carcinoma. World J Gastroenterol 21(2):549–555
Zheng HC, Li XH, Hara T et al, 2008, Mixed type gastric carcinoma exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch 452(5):525–534
GravalosC, JimenoA(2008)HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 19(9):1523–1529
Qiu M, Zhou Y, Zhong X et al, 2014, Lauren classification combined with HER2 status is a better prognostic factor in Chinese gastric cancer patients. BMC Cancer 14:823
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 197
EP 202
DI 10.1007/s12253-015-9996-6
PG 6
ER
PT J
AU Glowacka, I
Nowikiewicz, T
Siedlecki, Z
Hagner, W
Nowacka, K
Zegarski, W
AF Glowacka, Iwona
Nowikiewicz, Tomasz
Siedlecki, Zygmunt
Hagner, Wojciech
Nowacka, Krystyna
Zegarski, Wojciech
TI The Assessment of the Magnitude of Frontal Plane Postural Changes in Breast Cancer Patients After Breast-Conserving Therapy or Mastectomy – Follow-up Results 1 Year After the Surgical Procedure
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast conserving therapy; Mastectomy; Computed-assisted postural assessment; Body posture; Frontal plane
ID Breast conserving therapy; Mastectomy; Computed-assisted postural assessment; Body posture; Frontal plane
AB Breast cancer is the most common malignancy in Polish women. Management of breast cancer includes surgical treatment as well as adjuvant chemotherapy, radiotherapy, hormonal therapy, and combination regimens. One of the adverse consequences of oncological management of breast cancer may involve changes in frontal plane body posture. The objective of the study was to assess the frontal plane body posture changes in women treated for breast cancer. A prospective study including 101 of female breast cancer patients subjected to surgical treatment in the period from October 2011 to October 2012 (mastectomy was performed in 51 cases while breast conserving therapy was administered in the remaining 50 cases). The body posture in the frontal plane was assessed using the computerassisted postural assessment system with Moire fringe analysis. No statistically significant differences were observed in pre-operational postural parameters of interest. Exam II revealed highly significant differences in SLA values; results suggesting more pronounced dysfunction were observed in the MAS group. Exam III revealed highly significant differences in PIA, SH, SD and SLA values; results suggesting more pronounced dysfunction were observed in the MAS group. Undesirable postural changes occur both in women who were treated with radical mastectomy and in those who underwent breast-conserving surgery; breast-conserving surgery is associated with decreased severity in postural abnormalities;
C1 [Glowacka, Iwona] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of RehabilitationBydgoszcz, Poland.
[Nowikiewicz, Tomasz] Bydgoszcz Oncology Center, Clinical Department of Breast Cancers and Breast Reconstruction SurgeryBydgoszcz, Poland.
[Siedlecki, Zygmunt] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of NeurosurgeryBydgoszcz, Poland.
[Hagner, Wojciech] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of RehabilitationBydgoszcz, Poland.
[Nowacka, Krystyna] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of RehabilitationBydgoszcz, Poland.
[Zegarski, Wojciech] Medical College of the Nicolaus Copernicus University in Torun, Clinic and Chair of Oncological SurgeryBydgoszcz, Poland.
RP Glowacka, I (reprint author), Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of Rehabilitation, Bydgoszcz, Poland.
EM iwona.glowacka@cm.umk.pl
CR Devoogdt N, Van Kampen M, Christiaens MR et al, 2011, Shortand long-term recovery of upper limb function after axillary lymph node dissection. Eur J Cancer Care, Engl, 20:77–86
Favarao KU, Mantese JC, Barros AC, 2010, Shoulder mobility after axillary sentinel node biopsy for early infiltrating breast cancer treatment. Eur J Gynaecol Oncol 31:23–26
Yang EJ, Park WB, Seo KS et al, 2010, Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer surviviors: a prospective cohort study. J Surg Oncol 101:84–91
Ferrell BR, Grant MM, Funk B et al, 1997, Quality of life in breast cancer survivors as identified focus groups. Psychooncology 6:13–23
Crosible J, Kilbreath SL, Dylke E et al, 2010, Effect ofmastectomy on shoulder and spinal kinematics during bilateral upper-limb movement. Phys Ther 90:679–692
Crosible J, Kilbreath SL, Hollman L et al, 2008, Scapulohumeral rhythm and associated spinal motion. Clin Biomech 23:184–192
Keramopoulos A, Tsionou C, Minaretzis D et al, 1993, Arm morbidity following treatment of breast cancer with total axillary dissection: a multivariated approach. Oncology 50:445–449
McClure PW, Michener LA, Sennett BJ et al, 2001, Direct 3- dimensional measurement of scapular kinematics during dynamic movements in vivo. J Shoulder Elbow Surg 10:269–277
Bentzen SM, Dische S, 2000, Morbidity related to axillary irradiation in the treatment of breast cancer. Acta Oncol 39:337–347
Tanis PJ, Nieweg OE, Valdes Olmos RA, Kroon BB, 2001, Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg 192:399– 409
Tanis PJ, Nieweg OE, Valdes Olmos RA, 2001, History of sentinel node and validation of the technique. Breast Cancer Res 3:109–112
Zavagno G, Rubello D, Franchini Z et al, 2005, Axillary sentinel lymph nodes in breast cancer: a single lymphatic pathway drains the en tire mammary gland. Eur J Surg Oncol 31:479–484
Rietman JS, Dikstra PU, Hoekstra HJ et al, 2003, Late morbidity after treatment of breast cancer in relation to daily activities and quality of life: a systemic review. Eur J Surg Oncol 29:229–238
Hojan K, Wruk B, Stryla W, 2011, Wplyw leczenia raka piersi na dolegliwosci bolowe kregoslupa w odcinku ledzwiowokrzyzowym. Onkologia Polska 13:177–184
Ciesla S, Polom K, 2010, The effect of immediate breast reconstruction with Becker-25 prosthesis on the preservation of proper body posture in patients after mastectomy. Eur J Surg Oncol 36(7): 625–631
Bak M, Rostkowska E, 2000, The influence of using breast prothesis during the night on the changes of body posture among women after mastectomy. Fizjoterapia 8(4):11–15
Adderley-Kelly B, Williams-Stephens E, 2003, The relationsship between obesity and breast cancer. ABNF Journal 14(3):61–65
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Fisher B, Redmond C, Poisson R et al, 1989, Eight-year results of a randomised trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 320:822–828
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Clark AC, McColloch PB, Levine MN et al, 1992, Randomised clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 84:683–689
Veronesi U, Luini A, Del VecchioMet al, 1993, Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 328:1587–1589
Ragaz J, Jackson SM, Le N et al, 1997, Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337:956–962
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 203
EP 208
DI 10.1007/s12253-015-9995-7
PG 6
ER
PT J
AU Toth, D
Varga, Zs
Sebo,
Torok, M
Kovacs, I
AF Toth, Dezso
Varga, Zsolt
Sebo, Eva
Torok, Miklos
Kovacs, Ilona
TI Predictive Factors for Positive Margin and the Surgical Learning Curve in Non-Palpable Breast Cancer After Wire-Guided Localization – Prospective Study of 214 Consecutive Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Surgery; Non-palpable; Wire-guided localization; Learning curve
ID Breast cancer; Surgery; Non-palpable; Wire-guided localization; Learning curve
AB To investigate the most commonly used technique, the wire-guided localization (WGL) in non-palpable breast cancer. To analyze the effective factors on positive surgical margins in our practice and determine the surgical learning curve of this method. Prospective consecutive study was performed from January 2005 to December 2011. Inclusion criteria was a non-palpable breast lesion with malignancy on preoperative histology. All lesions were localized by ultrasound or stereotactic guided wire placement. Margins 1 mm or closer were accepted as positive margins which required reexcision. To determine the learning curve of WGL method we investigated the change in the reoperation rate after primary procedure performed by "high-volume" surgeon. Two hundred and fourteen consecutive patients were enrolled. In 23 patients (10.7 %) reexcision was needed. Positive surgical margins were significantly influenced by the patient’s age (p=0.03), tumor volume (p<=0.001), proportion of tumor volume/specimen volume (p<0.001), presence of DCIS (p<0.001), multifocality (p=0.03) and the learning curve (p=0.006) with univariate analysis. Only the tumor volume, presence of DCIS and the learning curve were proved as independent prognostic factor for reoperation by multivariate analysis. The reoperation rate decreased below 20 % after the fortieth operation. Results of our single institutional study suggest, that this localization technique can be performed safely with very good results after 40 procedures as a learning curve for surgeons.
C1 [Toth, Dezso] Kenezy Teaching Hospital, Department of General Surgery, 2-26 Bartok Street, 4031 Debrecen, Hungary.
[Varga, Zsolt] Kenezy Teaching Hospital, Department of General Surgery, 2-26 Bartok Street, 4031 Debrecen, Hungary.
[Sebo, Eva] Kenezy Teaching Hospital, Kenezy Breast Center, 21 Jeriko Street, 4032 Debrecen, Hungary.
[Torok, Miklos] Kenezy Teaching Hospital, Department of Pathology, 2-26 Bartok Street, 4031 Debrecen, Hungary.
[Kovacs, Ilona] Kenezy Teaching Hospital, Department of Pathology, 2-26 Bartok Street, 4031 Debrecen, Hungary.
RP Toth, D (reprint author), Kenezy Teaching Hospital, Department of General Surgery, 4031 Debrecen, Hungary.
EM detoth@gmail.com
CR ParkinM, Bray F, Ferlay J, Pisani P, 2002, Global cancer statistics. Cancer J Clin 55:74–108
Skinner KA, Silberman H, Sposto R, Silverstein MJ, 2001, Palpable breast cancers are inherently different from nonpalpable breast cancers. Ann Surg Oncol 8(9):705–710
Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ, 2000, Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990–8: comparison of observed with predicted mortality. BMJ 321:665–669
Gray RJ, Salud C, Nguyen K et al, 2001, Randomized prospective evaluation of a novel technique for biopsy or lumpectomy of nonpalpable breast lesions: radioactive seed versus wire localization. Ann Surg Oncol 8(9):711–715
Medina-Franco H, Abarca-Perez L, Garcia-Alvarez MN, Ulloa- Gomez JL, Romero-Trejo C, Sepulveda-Mendez J, 2008, Radioguided occult lesion localization, ROLL, versus wireguided lumpectomy for non-palpable breast lesions: a randomized prospective evaluation. J Surg Oncol 97(2):108–111
Ocal K, Dag A, Turkmenoglu O, Gunay EC, Yucel E, Duce MN, 2011, Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial. Clinics, Sao Paulo, 66(6):1003–1007
Lovrics PJ, Cornacchi SD, Farrokhyar F et al, 2009, The relationship between surgical factors and margin status after breastconservation surgery for early stage breast cancer. Am J Surg 197(6):740–746
Toth D, Sebo E, Sarkadi L, Kovacs I, Kiss C, Damjanovich L, 2012, Role of core needle biopsy in the treatment of radial scar. Breast 21(6):761–763
Postma EL,Witkamp AJ, van den BoschMA, Verkooijen HM, van Hillegersberg R, 2011, Localization of nonpalpable breast lesions. Expert Rev Anticancer Ther 11(8):1295–1302
Besic N, Zgajnar J, HocevarMet al, 2002, Breast biopsy with wire localization: factors influencing complete excision of nonpalpable carcinoma. Eur Radiol 12(11):2684–2689
Davis PS,Wechsler RJ, Feig SA, MarchDE, 1988)Migration of breast biopsy localization wire. AJR Am J Roentgenol 150(4):787–788
Rahusen FD, Bremers AJ, Fabry HF, van Amerongen AH, Boom RP, Meijer S, 2002, Ultrasound-guided lumpectomy of nonpalpable breast cancer versus wire-guided resection: a randomized clinical trial. Ann Surg Oncol 9:994–998
Homer MJ, 1983, Transection of the localization hooked wire during breast biopsy. Am J Roentgenol 141:929–930
Tykka H, Castren-Person M, Sjoblom M, 1993, Pneumothorax caused by hooked wire localization of an impalpable breast lesion detected by mammography. Breast 2:52–53
Jeevan R, Cromwell DA, Trivella M et al, 2012, Reoperation rates after breast conserving surgery for breast cancer among women in England: retrospective study of hospital episode statistics. BMJ 345:e4505
Takacs T, Paszt A, Simonka Z et al, 2013, Radioguided occult lesion localisation versus wire-guided lumpectomy in the treatment of non-palpable breast lesions. Pathol Oncol Res 19(2):267–273
Bernardi S, Bertozzi S, Londero AP, Gentile G, Giacomuzzi F, Carbone A, 2012, Incidence and risk factors of the intraoperative localization failure of nonpalpable breast lesions by radio-guided occult lesion localization: a retrospective analysis of 579 cases. World J Surg 36(8):1915–1921
Wazer DE, Schmidt-Ullrich RK, Ruthazer R et al, 1999, The influence of age and extensive intraductal component histology upon breast lumpectomy margin assessment as a predictor of residual tumor. Int J Radiat Oncol Biol Phys 45(4):885–891
Smitt MC, Horst K, 2007, Association of clinical and pathologic variables with lumpectomy surgicalmargin status after preoperative diagnosis or excisional biopsy of invasive breast cancer. Ann Surg Oncol 14(3):1040–1044
Sanchez C, Brem RF, McSwain AP, Rapelyea JA, Torrente J, Teal CB, 2010, Factors associated with re-excision in patients with early-stage breast cancer treated with breast conservation therapy. Am Surg 76(3):331–334
Lovrics PJ, Cornacchi SD, Vora R, Goldsmith CH, Kahnamoui K, 2011, Systematic review of radioguided surgery for non-palpable breast cancer. Eur J Surg Oncol 37(5):388–397
Del Turco MR, Ponti A, Bick U, Biganzoli L et al, 2010, Quality indicators in breast cancer care. Eur J Cancer 46(13):2344–2356
AhmedM, DouekM(2013, Radioactive seed localisation, RSL, in the treatment of non-palpable breast cancers: systematic review and meta-analysis. Breast 22(4):383–388
Postma EL, Verkooijen HM, van Esser S et al, 2012, Efficacy of ‘radioguided occult lesion localisation’, ROLL, versus ‘wire-guided localisation’, WGL, in breast conserving surgery for nonpalpable breast cancer: a randomised controlled multicentre trial. Breast Cancer Res Treat 136(2):469–478
Cleffken B, Postelmans J, Olde Damink S, Nap M, Schreutelkamp I, van der Bijl H, 2007, Breast-conserving therapy for palpable and nonpalpable breast cancer: can surgical residents do the job irrespective of experience? World J Surg 31(9):1731–1736
Landheer ML, Hoorntje LE, Klinkenbijl JH, Borel Rinkes IH, 2004, The surgical treatment of nonpalpable breast carcinoma in a university teaching hospital and a general teaching hospital by residents-in-training and surgeons; comparable results. Ned Tijdschr Geneeskd 148(35):1724–1727
Edge SB, Byrd DR, Compton CC et al, eds,, 2010, AJCC cancer staging manual, 7th edn. Springer, New York, pp 347–376
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 209
EP 215
DI 10.1007/s12253-015-9999-3
PG 7
ER
PT J
AU Ujj, Zs
Buglyo, G
Udvardy, M
Beyer, D
Vargha, Gy
Biro, S
Rejto, L
AF Ujj, Zsofia
Buglyo, Gergely
Udvardy, Miklos
Beyer, Daniel
Vargha, Gyorgy
Biro, Sandor
Rejto, Laszlo
TI WT1 Expression in Adult Acute Myeloid Leukemia: Assessing its Presence, Magnitude and Temporal Changes as Prognostic Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE WT1 gene; Overexpression; Quantitative real-time PCR; Acute myeloid leukemia
ID WT1 gene; Overexpression; Quantitative real-time PCR; Acute myeloid leukemia
AB Expression of the gene Wilms tumor 1 (WT1) has been suggested as a marker of minimal residual disease in acute myeloid leukemia (AML), but literature data are not without controversy. Our aimwas to assess the presence, magnitude and temporal changes of WT1 expression as prognostic factors. 60 AML patients were followed until death or the end of the 6-year observation period. Blood samples were taken at diagnosis, post-induction, during remission and in case of a relapse. Using quantitative real-time PCR, we determined WT1 expression from each sample, normalized it against the endogenous control gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and classified samples as negative, moderately positive or highly positive. We divided the patients into groups based on detected WT1 expression values, illustrated overall and disease-free survival on Kaplan-Meier curves, and compared differences between each group by the logrank test. Disappearance of WT1-positivity during chemotherapy had a favorable effect on survival. Interestingly, no difference was seen between the survivals of WT1-positive subgroups that expressed moderate or high levels of WT1 mRNA. A 1-log decrease in WT1 expression without becoming negative did not affect prognosis, either. Our results suggest that defining a cut-off value for WT1-positivity, rather than just using logarithmic figures of changes in gene expression, might have prognostic use in post-induction AML patients. We encourage further, larger-scale studies.
C1 [Ujj, Zsofia] University of Debrecen, Faculty of Medicine, Department of Hematology, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Buglyo, Gergely] University of Debrecen, Department of Human Genetics, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of Hematology, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Beyer, Daniel] University of Debrecen, Department of Human Genetics, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Vargha, Gyorgy] University of Debrecen, Department of Human Genetics, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Biro, Sandor] University of Debrecen, Department of Human Genetics, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
[Rejto, Laszlo] University of Debrecen, Faculty of Medicine, Department of Hematology, 98 Nagyerdei korut, 4028 Debrecen, Hungary.
RP Buglyo, G (reprint author), University of Debrecen, Department of Human Genetics, 4028 Debrecen, Hungary.
EM gbuglyo@hotmail.com
CR Rose EA, Glaser T, Jones C, Smith CL, Lewis WH, Call KM, Minden M, Champagne E, Bonetta L, Yeger H, Housman DE, 1990, Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms' tumor gene. Cell 60:495–508
CallKM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, 1990, Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60:509–520
Essafi A, Webb A, Berry RL, Slight J, Burn SF, Spraggon L, Velecela V, Martinez-Estrada OM, Wiltshire JH, Roberts SG, Brownstein D, Davies JA, Hastie ND, Hohenstein P, 2011, A wt1-controlled chromatin switching mechanism underpins tissuespecific wnt4 activation and repression. Dev Cell 21:559–574
Morrison AA, Viney RL, Ladomery MR, 2008, The posttranscriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta 1785:55–62
Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE, 1991, Alternative splicing and genomic structure of theWilms tumor gene WT1. Proc Natl Acad Sci U S A 88:9618–9622
Miller-Hodges E, Hohenstein P, 2012)WT1 in disease: shifting the epithelial-mesenchymal balance. J Pathol 226:229–240
Miwa H, Beran M, Aunders GF, 1992, Expression of the Wilms tumor gene, WT1, in human leukemias. Leukemia 6:405–409
Vidovic K, Svensson E, Nilsson B, Thuresson B, Olofsson T, Lennartsson A, Gullberg U, 2010, Wilms' tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells. Leukemia 24:992–1000
Bergmann L, Miething C, Maurer U, Brieger J, Karakas T, Weidmann E, Hoelzer D, 1997, High levels of Wilms' tumor gene, wt1, mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood 90:1217–1225
Gaiger A, Schmid D, Heinze G, Linnerth B, Greinix H, Kalhs P, Tisljar K, Priglinger S, Laczika K, Mitterbauer M, Novak M, Mitterbauer G,Mannhalter C, Haas OA, Lechner K, Jager U, 1998, Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia. Leukemia 12:1886–1894
Noronha SA, Farrar JE, Alonzo TA, Gerbing RB, Lacayo NJ, Dahl GV, Ravindranath Y, Arceci RJ, LoebDM(2009)WT1 expression at diagnosis does not predict survival in pediatric AML: a report from the children's oncology group. Pediatr Blood Cancer 53:1136–1139
Mossallam GI, Hamid TM, Mahmoud HK, 2013, Prognostic significance of WT1 expression at diagnosis and end of induction in Egyptian adult acute myeloid leukemia patients. Hematology 18: 69–73
Gray JX, McMillen L, Mollee P, Paul S, Lane S, Bird R, Gill D, Saal R, Marlton P, 2012, WT1 expression as a marker of minimal residual disease predicts outcome in acute myeloid leukemia when measured post-consolidation. Leuk Res 36:453–458
Andersson C, Li X, Lorenz F, Golovleva I, Wahlin A, Li A, 2012, Reduction in WT1 gene expression during early treatment predicts the outcome in patients with acute myeloid leukemia. Diagn Mol Pathol 21:225–233
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 217
EP 221
DI 10.1007/s12253-015-0002-0
PG 5
ER
PT J
AU Oh, RH
Choi, JY
Yoo, JN
Lee, HS
AF Oh, Rim Hye
Choi, Jin Youn
Yoo, Jin Nam
Lee, Hyung Sug
TI Leukemia Relapse-Associated Mutation of NT5C2 Gene is Rare in de Novo Acute Leukemias and Solid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Oh, Rim Hye] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Jin Youn] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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Tzoneva G, Perez-Garcia A, Carpenter Z, Khiabanian H, Tosello V, Allegretta M, Paietta E, Racevskis J, Rowe JM, Tallman MS, Paganin M, Basso G, Hof J, Kirschner-Schwabe R, Palomero T, Rabadan R, Ferrando A, 2013, Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med 19:368–371
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 223
EP 224
DI 10.1007/s12253-015-9965-0
PG 2
ER
PT J
AU Choi, RM
An, HCh
Yoo, JN
Lee, HS
AF Choi, Ryoung Mi
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of CAB39L, an Activator of LKB1 Tumor Suppressor, in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Ryoung Mi] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General SurgerySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Alessi DR, Sakamoto K, Bayascas JR, 2006, LKB1-dependent signaling pathways. Transcription 4:29–33
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 225
EP 226
DI 10.1007/s12253-015-9973-0
PG 2
ER
PT J
AU Lee, HJ
Kim, SM
Yoo, JN
Lee, HS
AF Lee, Hwa Ju
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Absence of KNSTRN Mutation, a Cutaneous Squamous Carcinoma-Specific Mutation, in Other Solid Tumors and Leukemias
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Lee, Hwa Ju] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Fang L, Seki A, Fang G, 2009, SKAP associates with kinetochores and promotes the metaphase-to-anaphase transition. Cell Cycle 8: 2819–2827.
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Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044-E1047.
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers Histopathology 60:943–952.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 227
EP 228
DI 10.1007/s12253-015-9993-9
PG 2
ER
PT J
AU Goodyer, M
Langabeer, ES
Haslam, K
Murphy, K
AF Goodyer, Matthew
Langabeer, E Stephen
Haslam, Karl
Murphy, Karen
TI The JAK2 V617F Allele Burden in Latent Myeloproliferative Neoplasms Presenting with Splanchnic Vein Thrombosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Goodyer, Matthew] St. Vincent’s University Hospital, Department of HaematologyDublin, Ireland.
[Langabeer, E Stephen] St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular DiagnosticsDublin, Ireland.
[Haslam, Karl] St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular DiagnosticsDublin, Ireland.
[Murphy, Karen] St. Vincent’s University Hospital, Department of HaematologyDublin, Ireland.
RP Langabeer, ES (reprint author), St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular Diagnostics, Dublin, Ireland.
EM slangabeer@stjames.ie
CR Sekhar M, McVinnie K, Burroughs AK, 2013, Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol 162: 730–747
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 229
EP 230
DI 10.1007/s12253-015-9994-8
PG 2
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Absence of PRKD1 Mutation, a Salivary Tumor-Specific Mutation, in Solid Tumors and Leukemias
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2016
VL 22
IS 1
BP 231
EP 232
DI 10.1007/s12253-015-0001-1
PG 1
ER
PT J
AU Jarosova, M
Kriegova, E
Schneiderova, P
Fillerova, R
Prochazka, V
Mikesova, M
Flodr, P
Indrak, K
Papajik, T
AF Jarosova, Marie
Kriegova, Eva
Schneiderova, Petra
Fillerova, Regina
Prochazka, Vit
Mikesova, Michaela
Flodr, Patrik
Indrak, Karel
Papajik, Tomas
TI A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Diffuse large B-cell lymphoma; BCL6 rearrangements; BCL2 rearrangements; Non-immunoglobulin gene translocations; Complex chromosomal changes
ID Diffuse large B-cell lymphoma; BCL6 rearrangements; BCL2 rearrangements; Non-immunoglobulin gene translocations; Complex chromosomal changes
AB BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the "major breakpoint region" encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with "alternative breakpoint cluster" located 245– 285 kb 5′ BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5′ untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5′ untranslated region of BCL6 and 5′ untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era.
C1 [Jarosova, Marie] Palacky University and University Hospital, Medical School, Department of Hemato-oncology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Kriegova, Eva] Palacky University Olomouc and the University Hospital Olomouc, Faculty of Medicine and Dentistry, Department of Immunology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Schneiderova, Petra] Palacky University Olomouc and the University Hospital Olomouc, Faculty of Medicine and Dentistry, Department of Immunology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Fillerova, Regina] Palacky University Olomouc and the University Hospital Olomouc, Faculty of Medicine and Dentistry, Department of Immunology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Prochazka, Vit] Palacky University and University Hospital, Medical School, Department of Hemato-oncology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Mikesova, Michaela] Palacky University and University Hospital, Medical School, Department of Hemato-oncology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Flodr, Patrik] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Indrak, Karel] Palacky University and University Hospital, Medical School, Department of Hemato-oncology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
[Papajik, Tomas] Palacky University and University Hospital, Medical School, Department of Hemato-oncology, Hnevotinska 3, 77900 Olomouc, Czech Republic.
RP Jarosova, M (reprint author), Palacky University and University Hospital, Medical School, Department of Hemato-oncology, 77900 Olomouc, Czech Republic.
EM marie.jarosova@fnol.cz
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 233
EP 243
DI 10.1007/s12253-015-9972-1
PG 11
ER
PT J
AU Shao, QQ
Zhang, TP
Zhao, WJ
Liu, ZW
You, L
Zhou, L
Guo, JCh
Zhao, YP
AF Shao, Qian-Qian
Zhang, Tai-Ping
Zhao, Wen-Jing
Liu, Zi-Wen
You, Lei
Zhou, Li
Guo, Jun-Chao
Zhao, Yu-Pei
TI Filamin A: Insights into its Exact Role in Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Filamin A; Cancer metastasis; Localization; Nucleus; Cytoplasm
ID Filamin A; Cancer metastasis; Localization; Nucleus; Cytoplasm
AB Filamin A (FlnA) is a well-known actin crosslinking protein. It serves as a scaffold for over 90 binding partners and involves in multiple cell functions, of which cell migration and adhesion is especially critical. Recently, its role in the cell has come under scrutiny for FlnA’s involvement in cancer development. Originally revealed as a cancerpromoting protein, FlnA actually plays a dual role in cancers. When localized to the cytoplasm, FlnA has a tumorpromoting effect by interacting with signaling molecules. While once localized to the nucleus, it may act to suppress tumor growth and inhibit metastasis by interacting with transcription factors. Thus drugs that can cause FlnA to transpose from cytoplasm to nucleus could be a promising treatment for cancers. Study to this end is on the way in prostate cancer and the results are encouraging. FlnA has been studied in large categories of cancers, such as prostate cancer, breast cancer, melanoma, lung cancer, etc. However, most studies did not evaluate the differences that arise from the localization of the protein, which was a great pity! What’s more, although FlnA’s is undoubtedly important in cancer invasion and metastasis, both preclinical and clinical researches are very rare in some highly metastatic cancers, such as pancreatic cancer. In this mini-review, we give a comprehensive summary of FlnA’ s expression in cancers. Where available, we also indicate the correlation of FlnA with cancer stages and patient prognosis, and clarify its localization (nucleus/cytoplasm) and its dual role (promote/suppress) in different cancers.
C1 [Shao, Qian-Qian] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Zhang, Tai-Ping] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Zhao, Wen-Jing] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Liu, Zi-Wen] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[You, Lei] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Zhou, Li] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Guo, Jun-Chao] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
[Zhao, Yu-Pei] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuaifuyuan Wangfujing, 100730 Beijing, China.
RP Guo, JCh (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
EM gjcpumch@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 245
EP 252
DI 10.1007/s12253-015-9980-1
PG 8
ER
PT J
AU Zeng, H
Zhang, Z
Dai, X
Chen, Y
Ye, J
Jin, Z
AF Zeng, Haibin
Zhang, Zhong
Dai, Xiaoming
Chen, Yongzhong
Ye, Jianhua
Jin, Zhixin
TI Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; microRNA-199b-5p; Clinicopathological characteristics; Prognosis; Carcinogenesis
ID Osteosarcoma; microRNA-199b-5p; Clinicopathological characteristics; Prognosis; Carcinogenesis
AB MicroRNA (miR)-199b-5p has been reported to be upregulated in human osteosarcoma tissues and participate in the Notch signaling in osteosarcoma cells. This study was aimed to investigate the associations of miR-199b-5p expression with tumor progression of primary osteosarcoma, and to deepen the understanding of its involvement in carcinogenesis. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect expression levels of miR-199b-5p in 98 osteosarcoma and corresponding adjacent normal tissues. Then, the correlations of its expression with clinicopathological characteristics and patient prognosis were statistically analyzed. Moreover, in vitro assays were performed to assess the effects of miR-199b-5p on the proliferation, migration and invasion of two human osteosarcoma cell lines MG63 and U2OS. Compared to normal controls, miR- 199b-5p expression was significantly upregulated in osteosarcoma tissues (P<0.001). In addition, the expression levels of miR-199b-5p in osteosarcoma patients with high tumor grade (P=0.008), positive metastasis (P=0.001) and positive recurrence (P=0.001) were markedly higher than those with low tumor grade, negative metastasis and negative recurrence. Moreover, osteosarcoma patients with high miR-199b-5p expression showed shorter overall survival (P<.001) and shorter disease-free survival (P<0.001) than those with low expression. Furthermore, the inhibition of miR-199b-5p significantly suppressed cell proliferation, and reduced the migratory and invasive abilities of osteosarcoma cells. This study offer the convincing evidence for the first time that the increased expression of miR-199b-5p may play crucial roles in aggressive progression and poor prognosis of human osteosarcoma. miR- 199b-5p may function as an oncogene by positively regulating the malignant potentials of this neoplasm.
C1 [Zeng, Haibin] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
[Zhang, Zhong] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
[Dai, Xiaoming] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
[Chen, Yongzhong] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
[Ye, Jianhua] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
[Jin, Zhixin] Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
RP Zeng, H (reprint author), Fuzhou General Hospital of Nanjing Military Region, 476 Clinical Division, Department of Orthopedics, 350002 Fuzhou, China.
EM Zenghaib139@163.com
CR Marina N, Gebhardt M, Teot L, Gorlick R, 2004, Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441
Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G, 2006, Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 32:423–436
Bielack SS, Marina N, Ferrari S, 2008, Osteosarcoma: the same old drugs or more? J Clin Oncol 26:3102–3103
Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF, 2011, The molecular pathogenesis of osteosarcoma: a review. Sarcoma 2011:959248
Kansara M, ThomasDM(2007, Molecular pathogenesis of osteosarcoma. DNA Cell Biol 26:1–18
Carrington JC, Ambros V, 2003, Role of microRNAs in plant and animal development. Science 301:336–338
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Andolfo I, Liguori L, De Antonellis P, 2012, The micro-RNA 199b-5p regulatory circuit involves Hes1, CD15, and epigenetic modifications in medulloblastoma. Neuro Oncol 14:596– 612
Lauvrak SU, Munthe E, Kresse SH, Stratford EW, Namlos HM, Meza-Zepeda LA, Myklebost O, 2013, Functional characterisation of osteosarcoma cell lines and identification ofmRNAs and miRNAs associated with aggressive cancer phenotypes. Br J Cancer 109: 2228–2236
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 253
EP 260
DI 10.1007/s12253-015-9901-3
PG 8
ER
PT J
AU Xu, L
Tang, W
AF Xu, Liping
Tang, Wenru
TI Associations of Polymorphisms in mir-196a2, mir-146a and mir-149 with Colorectal Cancer Risk: A Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mir-196a2; mir-146a; mir-149; CRC; SNP
ID mir-196a2; mir-146a; mir-149; CRC; SNP
AB MicroRNAs (miRNAs) are non-coding RNAs which act as tumor suppressors or oncogenes. And single nucleotide polymorphism (SNP) in miRNA regions is one type of genetic variations in human genome. Various studies have investigated the associations of miRNAs SNP and kinds of cancers. In this article, we searched eligible studies to explore the relationships between mir-196a2 /mir-146a /mir- 149 polymorphisms and colorectal cancer (CRC). A literature search of PubMed, Web of Science and ScienceDirect was conducted to identify all relevant studies. Three genetic models with pooled ratio and 95 % confidence interval were used to evaluate the associations. We found that mir-196a2 polymorphism was significantly associated with CRC in Asian group (additive model: OR=1.197, 95 %CI 1.084~ 1.32, P<0.001; dominant model: OR=1.247, 95 %CI 1.065 ~1.46, P=0.006; recessive model: OR=1.298, 95 %CI 1.101 ~1.531, P=0.002). And no associations were observed between SNPs of mir-146a, mir-149 and CRC in three genetic models.We also found CRC risk was not associated with mir- 146a and mir-149 polymorphisms in population subgroup analysis. The current meta-analysis suggests that mir-196a2 polymorphism is associated with CRC, especially in Asian group. While, no associations have been found between mir- 146a /mir-149 polymorphisms and CRC.
C1 [Xu, Liping] Kunming University of Science and Technology, Medical Faculty, Laboratory of Molecular Genetics of Aging & Tumor, Chenggong Campus, 727 South Jingming Road, 650500 Kunming, Yunnan, China.
[Tang, Wenru] Kunming University of Science and Technology, Medical Faculty, Laboratory of Molecular Genetics of Aging & Tumor, Chenggong Campus, 727 South Jingming Road, 650500 Kunming, Yunnan, China.
RP Tang, W (reprint author), Kunming University of Science and Technology, Medical Faculty, Laboratory of Molecular Genetics of Aging & Tumor, 650500 Kunming, China.
EM 531081047@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 261
EP 267
DI 10.1007/s12253-014-9843-1
PG 7
ER
PT J
AU Giaginis, C
Alexandrou, P
Poulaki, E
Delladetsima, I
Troungos, C
Patsouris, E
Theocharis, S
AF Giaginis, Constantinos
Alexandrou, Paraskevi
Poulaki, Elpida
Delladetsima, Ioanna
Troungos, Constantinos
Patsouris, Efstratios
Theocharis, Stamatios
TI Clinical Significance of EphB4 and EphB6 Expression in Human Malignant and Benign Thyroid Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ephrin receptors; Thyroid malignancy; Clinicopathological parameters; Immunohistochemistry; Papillary carcinoma; Hyperplastic nodule
ID Ephrin receptors; Thyroid malignancy; Clinicopathological parameters; Immunohistochemistry; Papillary carcinoma; Hyperplastic nodule
AB Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of EphB4 and EphB6 protein expression in human malignant and benign thyroid lesions. EphB4 and EphB6 protein expression was assessed immunohistochemically on paraffinembedded thyroid tissues obtained from 127 patients with benign (n=71) and malignant (n=56) thyroid lesions. Enhanced EphB4 and EphB6 expression was more frequently observed in malignant compared to benign thyroid lesions (p=0.0508 and p=0.0006, respectively). EphB4 and EphB6 expression also provided a distinct discrimination between papillary carcinoma and hyperplastic nodules (p=0.0302 and p=0.0013, respectively). In malignant thyroid lesions, enhanced EphB4 expression was significantly associated with larger tumor size (p=0.0366). Enhanced EphB6 expression was significantly associated with larger tumor size (p=0.0366), the presence of lymph node metastases (p=0.0023), the presence of capsular (p=0.0038), lymphatic (p=0.0053) and vascular invasion (p=0.0018) and increased risk of recurrence rate (p=0.0038). The present study supported evidence that EphB4 and mainly EphB6 may participate in the malignant thyroid transformation, reinforcing their utility as useful biomarkers and possible therapeutic targets in this type of neoplasia.
C1 [Giaginis, Constantinos] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
[Alexandrou, Paraskevi] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
[Poulaki, Elpida] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
[Delladetsima, Ioanna] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
[Troungos, Constantinos] University of Athens, Medical School, Department of BiochemistryAthens, Greece.
[Patsouris, Efstratios] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
[Theocharis, Stamatios] University of Athens, Medical School, First Department of Pathology, 75 M. Asias str., 11527 Goudi, Athens, Greece.
RP Theocharis, S (reprint author), University of Athens, Medical School, First Department of Pathology, 11527 Goudi, Greece.
EM stamtheo@med.uoa.gr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 269
EP 275
DI 10.1007/s12253-014-9879-2
PG 7
ER
PT J
AU Li, Y
Dong, M
Sheng, W
Huang, L
AF Li, Yuji
Dong, Ming
Sheng, Weiwei
Huang, Longping
TI Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carbonic anhydrase IX; Pancreatic cancer; Invasion; Migration
ID Carbonic anhydrase IX; Pancreatic cancer; Invasion; Migration
AB The aim of this study was to study the effects of carbonic anhydrase IX (CA IX) towards the invasion and metastasis of pancreatic cancer. The expressions of CA IX in 58 cases of pancreatic cancer and paired paracancerous normal tissues, obtained from 2005 to 2012 in the first Affiliated Hospital of China Medical University, were detected, as well as its expressions in different pancreatic cancer cell lines, aiming to detect the impacts of CA IX silencing towards the invasion and metastasis of pancreatic cancer cells. The CA IX expressions in 58 pancreatic cancer cases were higher than those in the paired paracancerous normal tissues (P<0.01), and positively correlated with the tumor size and the UICC staging UICC (P<0.05), the multivariate analysis showed that the high expression of CA IX was the independent risk factor towards the prognosis of pancreatic cancer (P<0.05). The CA IX was highly expressed in AxPC–1 and Miapaca–2, and the interference effects were significant. CA IX silencing could significantly inhibit the invasion and metastasis of AxPC-1 and Miapaca. We support a pro-tumor role of CA IX in the development and progression of pancreatic cancer.
C1 [Li, Yuji] China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
[Dong, Ming] China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
[Sheng, Weiwei] China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
[Huang, Longping] China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
RP Dong, M (reprint author), China Medical University, The First Affiliated Hospital, Department of General Surgery, 110001 Shenyang, China.
EM mingdongcn@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 277
EP 286
DI 10.1007/s12253-015-9935-6
PG 10
ER
PT J
AU Shastry, HA
Thota, B
Mallavarapu, RS
Arivazhagan, A
Santosh, V
AF Shastry, H Arun
Thota, Balaram
Mallavarapu, R Srividya
Arivazhagan, Arimappamagan
Santosh, Vani
TI Nuclear Protein Phosphatase 1 α (PP1A) Expression is Associated with Poor Prognosis in p53 Expressing Glioblastomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; Prognosis; TP53; Protein phosphatase 1 α; PPP1CA
ID Glioblastoma; Prognosis; TP53; Protein phosphatase 1 α; PPP1CA
AB Background: Protein phosphatase 1 α (PP1A) is an enzyme intimately associated with cell cycle, the over expression of which has been demonstrated in glioblastoma (GBM). Further, the nuclear expression of PP1A has been shown to be highly specific to GBM. In addition, PP1A has been shown to be a connecting molecule in the p53 containing GBM sub network. In view of these, we evaluated the prognostic relevance of PP1A. Methods: GBM tissues were examined for protein expression of PP1A by immunohistochemistry (IHC). Nuclear expression of PP1A was scored in all tumor tissue samples. Survival analyses were performed by Cox-Regression and Kaplan-Meier survival analysis with Log Rank tests. IDH1, ATRX and p53 IHC and stratification of all GBM cases were performed and subgroup specific evaluation of nuclear PP1A correlation with overall and progression free survival was performed. Results: PP1A protein expression showed no correlation with prognosis in all cases of GBM or on stratification based on IDH1 or ATRX expression. However on p53 stratification nuclear PP1A expression emerged as strong independent predictor of poor overall survival only in p53 positive GBMs both in univariate and multivariate analysis. Conclusions: While PP1A expression uniquely associates with poor prognosis only in p53 expressing GBMs, there is a notable absence of such correlation in p53 negative GBMs; thus skewing the overall relation of this molecule with prognosis in GBM. PP1A emerging as a strong prognostic marker in p53 expressing GBMs, enables us to foresee this molecule as a potential therapeutic target.
C1 [Shastry, H Arun] National Institute of Mental Health and Neurosciences (NIMHANS), Department of Clinical Neurosciences, Hosur RoadBangalore, India.
[Thota, Balaram] National Institute of Mental Health and Neurosciences, Department of Neuropathology, Hosur RoadBangalore, India.
[Mallavarapu, R Srividya] National Institute of Mental Health and Neurosciences, Department of Neuropathology, Hosur RoadBangalore, India.
[Arivazhagan, Arimappamagan] National Institute of Mental Health and Neurosciences, Department of Neurosurgery, Hosur RoadBangalore, India.
[Santosh, Vani] National Institute of Mental Health and Neurosciences (NIMHANS), Department of Clinical Neurosciences, Hosur RoadBangalore, India.
RP Santosh, V (reprint author), National Institute of Mental Health and Neurosciences (NIMHANS), Department of Clinical Neurosciences, Bangalore, India.
EM vani.santosh@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 287
EP 292
DI 10.1007/s12253-015-9928-5
PG 6
ER
PT J
AU Marton, I
Krenacs, L
Bagdi, E
Bakos, A
Demeter, J
Borbenyi, Z
AF Marton, Imelda
Krenacs, Laszlo
Bagdi, Eniko
Bakos, Annamaria
Demeter, Judit
Borbenyi, Zita
TI Clinical and Molecular Diagnostic Evaluation of Systemic Mastocytosis in the South-Eastern Hungarian Population Between 2001–2013 – A Single Centre Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myeloproliferative neoplasm; Mastocytosis; KIT D816V mutation; Orphan disease
ID Myeloproliferative neoplasm; Mastocytosis; KIT D816V mutation; Orphan disease
AB Systemic mastocytosis (SM) is a rare chronic myeloproliferative neoplasm with only limited epidemiologic data published so far. We aimed to analyze the clinical and molecular diagnostic features, and the prognosis and cumulative incidence of SM cases in a cohort of south-eastern Hungarian patients of 13 year follow up. In the period 2001–2013, 35 consecutive SM cases were diagnosed in our regional centre. Immunophenotype, KIT D816V mutation frequency and clinical characteristics, and the prognosis impact of clinical subtypes were tested and compared with published data. Indolent SM (ISM) was diagnosed in 14 patients, SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 15 patients and aggressive SM (ASM) in 6 patients. The KIT D816V mutation was found in 11/14 (78 %) of the ISM cases, in 12/15 (80 %) of the SMAHNMD cases and in 5/6 (83 %) of the ASM cases. The life expectancy of ISM patients was better, whereas the SMAHNMD and ASM groups exhibited a reduced median survival. The cumulative incidence for 13 year of the SM was 0.27/10,000. We detected lower 13 year cumulative SM incidence than of published epidemiologic data due to in our analyses involved only those patients who had bone marrow biopsy and histopathologically confirmed SM. This clinical overview clearly showed that the clinical characteristics differ between ISM (UP, anaphylaxis and osteoporosis) and SMAHNMD/ ASM (cytopenia, eosinophilia and splenomegaly).
C1 [Marton, Imelda] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Bagdi, Eniko] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Bakos, Annamaria] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
RP Marton, I (reprint author), University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Szeged, Hungary.
EM imeldamarton@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 293
EP 299
DI 10.1007/s12253-015-9948-1
PG 7
ER
PT J
AU Mendes, J
Goncalves, CA
Alves, R
Jorge, J
Pires, A
Ribeiro, A
Sarmento-Ribeiro, BA
AF Mendes, Jose
Goncalves, Cristina Ana
Alves, Raquel
Jorge, Joana
Pires, Ana
Ribeiro, Ana
Sarmento-Ribeiro, Bela Ana
TI L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diffuse Large B-cell Lymphoma; Burkitt’s lymphoma; Everolimus; L744; 832; Apoptosis
ID Diffuse Large B-cell Lymphoma; Burkitt’s lymphoma; Everolimus; L744; 832; Apoptosis
AB Non-Hodgkin Lymphoma (NHL) constitutes a very heterogeneous group of diseases with different aggressiveness. Diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) are two clinically aggressive lymphomas from the germinal center, very heterogeneous and with different genetic signatures. Several intracellular pathways are involved in lymphomagenesis, being BCR/PI3K/AKT/mTOR and RAS/RAF pathways the most frequently ones. In this context the therapeutic potential of a mTOR inhibitor – everolimus – and a RAS/RAF pathway inhibitor – L744,832 – was evaluated in two NHL cell lines. Farage and Raji cells were cultured in the absence and presence of several concentrations of everolimus and L744,832 in monotherapy and in combination with each other, as well as in association with the conventional chemotherapy drug vincristine. Our results show that everolimus and L744,832 induce antiproliferative and cytotoxic effect in a time-, dose-, and cell line-dependent manner, inducing cell death mainly by apoptosis. A potentiation effect was observed when the drugs were used in combination. In conclusion, the results suggest that everolimus and L744, 832, alone or in combination, could provide therapeutic benefits in these subtypes of NHL.
C1 [Mendes, Jose] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Goncalves, Cristina Ana] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Alves, Raquel] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Jorge, Joana] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Pires, Ana] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Ribeiro, Ana] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
[Sarmento-Ribeiro, Bela Ana] Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.
RP Sarmento-Ribeiro, BA (reprint author), Faculty of Medicine University of Coimbra – FMUC, University Clinic of Hematology and Applied Molecular Biology, 3000-548 Coimbra, Portugal.
EM absarmento@fmed.uc.pt
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 301
EP 309
DI 10.1007/s12253-015-9998-4
PG 9
ER
PT J
AU Nabi, Sh
Kahlon, P
Bozorgnia, F
Arshad, A
Mikkelsen, T
Donthireddy, V
AF Nabi, Shahzaib
Kahlon, Pushpinderdeep
Bozorgnia, Farshid
Arshad, Adeel
Mikkelsen, Tom
Donthireddy, Vijayalakshmi
TI Predictors of Venous Thromboembolism in Patients with Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GBM; Venous thromboembolism; KPS scale; Bevacizumab
ID GBM; Venous thromboembolism; KPS scale; Bevacizumab
AB To evaluate different risk factors associated with development of venous thromboembolism (VTE) in patients with Glioblastoma (GBM). A retrospective chart review was performed to include patients diagnosed with GBM from 2001 to 2011. Cases (n = 162) were defined as patients with GBM who developed VTE after diagnosis of GBM. Controls (n = 840) were defined as patients with GBM with no history of VTE. Data was collected for multiple variables including age, gender, race, length of hospital stay after brain biopsy, total number of hospital admissions unrelated to VTE, Karnofsky Performance Status (KPS), use of Bevacizumab and any bleeding episodes. Patients with GBM who had VTE had poorer KPS scores, with the majority (57 %) being in between 40 and 70, as compared to the controls where majority (82 %) had better performance (KPS 80-100). For every one year increase in age, the odds of developing VTE increased by 3%(OR 1.03, 95%CI 1.02-1.04, p < 0.001) with the mean age being 61.8 ± 11.4 years. GBM patients who developed a VTE were found to have greater number of hospital admissions (OR 1.43, 95%CI 1.33-1.53, p < 0.001) and longer stays in hospital after GBM biopsy (OR 1.14, 95%CI 1.09-1.18, p < 0.001). Patients receiving Bevacizumab were more likely to develop VTE (OR 1.79, 95%CI 1.21-2.64, p < 0.001) and were more likely to have a bleed (OR 3.78, 95 % CI 2.70-5.30, p < 0.001). Patients with GBM are at a higher risk of developing VTE. The risk is higher in older patients who require multiple hospital admissions, longer duration of hospital stays related to GBM biopsy, and in patients with lower KPS scores. Bevacizumab use is related to a higher incidence of VTE as well as bleeds. This study suggests that a more aggressive strategy for VTE prophylaxis should be considered in GBM patients with risk factors for VTE.
C1 [Nabi, Shahzaib] Henry Ford Health System / Wayne State University, Department of Internal Medicine, 2799 West Grand Boulevard, CFP 1, 48202 Detroit, MI, USA.
[Kahlon, Pushpinderdeep] Henry Ford Health System / Wayne State University, Department of Internal Medicine, 2799 West Grand Boulevard, CFP 1, 48202 Detroit, MI, USA.
[Bozorgnia, Farshid] Wayne State University, School of MedicineDetroit, MI, USA.
[Arshad, Adeel] Weill Cornell University, Hamad Medical Corporation, Department of Internal MedicineDoha, Qatar.
[Mikkelsen, Tom] Henry Ford Health System / Wayne State University, Hermelin Brain Tumor CenterDetroit, MI, USA.
[Donthireddy, Vijayalakshmi] Henry Ford Health System / Wayne State University, Department of Hematology-OncologyDetroit, MI, USA.
RP Nabi, Sh (reprint author), Henry Ford Health System / Wayne State University, Department of Internal Medicine, 48202 Detroit, USA.
EM snabi1@hfhs.org
CR Thaler J, Ay C, Kaider A, Reitter EM, Haselbock J, Mannhalter C, Zielinski C, Marosi C, Pabinger I, 2014, Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro-Oncology 16(12):1645– 1651., DOI 10.1093/neuonc/nou106
Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH, 2007, Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5(3):632–634., DOI 10.1111/j.1538-7836.2007.02374.x
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 311
EP 316
DI 10.1007/s12253-015-0008-7
PG 6
ER
PT J
AU Burada, F
Ciurea, EM
Nicoli, R
Streata, I
Vilcea, DI
Rogoveanu, I
Ioana, M
AF Burada, Florin
Ciurea, Eugen Marius
Nicoli, Raluca
Streata, Ioana
Vilcea, Dan Ionica
Rogoveanu, Ion
Ioana, Mihai
TI ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Autophagy; ATG16L1 gene; Polymorphism; Gene expression
ID Gastric cancer; Autophagy; ATG16L1 gene; Polymorphism; Gene expression
AB Gastric cancer is a major leading cause of cancerrelated death in both sexes in Europe. The role of autophagy process in carcinogenesis remains unclear and there is increasing evidence that Helicobacter pylori is a key player in modulating autophagy in gastric carcinogenesis. The aim of this studywas to assess the potential association of ATG16L1 T300A polymorphismwith susceptibility of gastric cancer, and further to analyze the expression profile of ATG16L1 gene in paired tumoral and peritumoral gastric tissue. A total of 108 patients diagnosed with gastric cancer and 242 healthy controlswere enrolled.ATG16L1 T300A polymorphism was detected using TaqMan genotyping assay containing primers and specific probes for A and G allele, respectively. ATG16L1 mRNA level was evaluated in 34 paired tumoral and peritumoral tissues using qRT-PCR. We found a significant association for both carriers of AG (OR 0.52, 95 % CI: 0.30–0.91, p = 0.02) and GG genotype (OR 0.53, 95 % CI: 0.28–0.98, p = 0.043), these were at a lower risk for gastric cancer when compared with the wild-type AA genotype. The strongest association was observed in a dominant model, the carriers of G allele were protected against gastric cancer (OR 0.52, 95 % CI: 0.13–0.88, p = 0.013). In a stratified analyse, the association was limited to non-cardia type and intestinal type. ATG16L1 gene expression was detected in both tumor and peritumoral tissues, with the mRNA-ATG16L1 levels significantly higher in tumor sample. Our results suggest that ATG16L1 T300A polymorphismmay be associatedwith gastric carcinogenesis.
C1 [Burada, Florin] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
[Ciurea, Eugen Marius] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
[Nicoli, Raluca] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
[Streata, Ioana] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
[Vilcea, Dan Ionica] University of Medicine and Pharmacy of Craiova, Department of Surgery, Petru Rares street no 2-4, 200349 Craiova, Romania.
[Rogoveanu, Ion] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
[Ioana, Mihai] University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, 1 May street no 66Craiova, Romania.
RP Burada, F (reprint author), University of Medicine and Pharmacy of Craiova, Research Center of Gastroenterology and Hepatology, Craiova, Romania.
EM buradaflorin@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 317
EP 322
DI 10.1007/s12253-015-0006-9
PG 6
ER
PT J
AU Zidi, S
Sghaier, I
Gazouani, E
Mezlini, A
Yacoubi-Loueslati, B
AF Zidi, Sabrina
Sghaier, Ikram
Gazouani, Ezzedine
Mezlini, Amel
Yacoubi-Loueslati, Besma
TI Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Toll-like receptor; Cervical cancer; Gene polymorphism; FIGO stage
ID Toll-like receptor; Cervical cancer; Gene polymorphism; FIGO stage
AB Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (−196 to −174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16–0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+ IV); C/C versuss C/T [p = 0.033; OR: 2.03(1.00–4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00–3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58– 13.06)], [p = 0.001; OR: 3.49(1.44–8.45)] and in stage (III+ IV) [p = 0.038; OR: 3.77(0.87–16.29)], [p = 0.007; OR: 5.21(1.65–16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/ Del genotype is associated with tumor evolution to stage (III+ IV) [p = 0.003; OR: 3.00 (1.22–7.35)] and the genotypes Gly/ Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Sghaier, Ikram] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
[Gazouani, Ezzedine] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Yacoubi-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 2092 El MANAR I, 1092 Tunis, Tunisia.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 323
EP 330
DI 10.1007/s12253-015-0009-6
PG 8
ER
PT J
AU Zhu, L
Jing, S
Wang, B
Wu, K
Shenglin, M
Zhang, Sh
AF Zhu, Lucheng
Jing, Saisai
Wang, Bing
Wu, Kan
Shenglin, Ma
Zhang, Shirong
TI Anti-PD-1/PD-L1 Therapy as a Promising Option for Non-Small Cell Lung Cancer: a Single arm Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PD-1; PD-L1; Non-small cell lung cancer; Checkpoint inhibitor; Meta-analysis
ID PD-1; PD-L1; Non-small cell lung cancer; Checkpoint inhibitor; Meta-analysis
AB Anti-PD-1/PD-L1 antibodies showed satisfactory efficacy in treating non-small-cell lung cancer. We conducted this meta-analysis to explore the advantage subtypes and best therapeutic modalities of Anti-PD-1/PD-L1 therapy on NSCLC. A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, and the Cochrane Library. The pooled ORR, 6-month progressionfree survival rate (PFSR6m), and 1-year overall survival rate (OSR1y) were calculated and compared. 15 trials were included in this meta-analysis. Our analyses demonstrated the pooled ORR of 1st line and 2nd or more line anti-PD-1/PDL1 therapy were 36.5 % (21.9–51.0 %) and 17.0 % (14.3– 19.7 %), respectively. While the difference was significant (Z = 3.31, p < 0.001). The pooled ORR for non-squamous and squamous cell lung cancer were 18.5 % (16.0–21.1 %) and 17.9 % (14.4–21.5 %), respectively. The difference was not significant (Z = 0.27, p = 0.791). The pooled ORR for PDL1 positive and negative patients were 29.6 % (21.6–37.6 %) and 13.5 % (10.6–16.3 %), respectively. The difference was significant (Z = 4.39, p < 0.001). The PFSR6m for PD-L1 positive and negative NSCLC were 50.0 % (40.5–62.3 %) and 27.0 % (19.2–34.7 %). The difference was significant (Z = 3.72, p < 0.001). The OSR1y for PD-L1 positive and negative NSCLC were 66.8 % (44.8 %-88.9 %) and 54.0 % (32.6–75.3 %). The difference was not significant (Z = 0.77, p = 0.441). Anti-PD-1/PD-L1 antibody can serve as a promising treatment option for NSCLC. Patients with positive PD-L1 expression may benefit more from anti-PD-1/PD-L1 therapy. 1st-line anti-PD-1/ PD-L1 therapy can be chosen as the best modality. Squamous cell lung cancer also benefit from anti-PD-1/ PD-L1 therapy.
C1 [Zhu, Lucheng] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Jing, Saisai] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Wang, Bing] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Wu, Kan] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Shenglin, Ma] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Zhang, Shirong] Hangzhou First People’s Hospital, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
RP Shenglin, M (reprint author), Hangzhou First People’s Hospital, 310006 Hangzhou, China.
EM mashenglin@outlook.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 331
EP 339
DI 10.1007/s12253-015-0011-z
PG 9
ER
PT J
AU Mallak, JA
Abbaszadegan, RM
Khorasanizadeh, NP
Forghanifard, MM
AF Mallak, Javdani Afsaneh
Abbaszadegan, Reza Mohammad
Khorasanizadeh, Naeemi Pegah
Forghanifard, Mahdi Mohammad
TI Contribution of EVX1 in Aggressiveness of Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EVX1; BMP signaling pathway; Epithelial mesenchymal transition; Escc
ID EVX1; BMP signaling pathway; Epithelial mesenchymal transition; Escc
AB Homeobox genes play an overruling role in the regional cell fate determination during development. EVX1 is known as a new target gene of BMP signaling pathway, a group of morphogens which are making the largest subset within the transformation growth factor beta (TGF-β) superfamily. In this study, we aimed to enlighten the expression level of EVX1 in esophageal squamous cell carcinoma (ESCC) and to disclose its apparent roles in maintenance and progression of the disease. The expression level of EVX1 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients using relative comparative real-time PCR. The importance of EVX1 in development and cancer was also reviewed. EVX1 was underexpressed in 70 % of tumor samples. There was a significant correlation between down-regulation of EVX1 and lymph node metastasis of tumor cells (p = 0.027). Furthermore, EVX1 underexpression was significantly correlated with depth of tumor cell invasion (P = 0.037). To the best of our knowledge, this is the first report highlighting EVX1 expression in ESCC to date. The clinicopathological relevance of EVX1 mRNA expression in ESCC targeted this gene as a new independent molecular marker for advanced tumor, which determine the characteristics and behavior of aggressive ESCC.
C1 [Mallak, Javdani Afsaneh] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human GeneticsMashhad, Iran.
[Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human GeneticsMashhad, Iran.
[Khorasanizadeh, Naeemi Pegah] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human GeneticsMashhad, Iran.
[Forghanifard, Mahdi Mohammad] Islamic Azad University, Damghan Branch, Department of Biology, Cheshmeh-Ali Boulevard, Sa’dei SquareDamghan, Iran.
RP Forghanifard, MM (reprint author), Islamic Azad University, Damghan Branch, Department of Biology, Damghan, Iran.
EM forghanifard@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 341
EP 347
DI 10.1007/s12253-015-0005-x
PG 7
ER
PT J
AU Helpap, B
Ringli, D
Tonhauser, J
Poser, I
Breul, J
Gevensleben, H
Seifert, HH
AF Helpap, Burkhard
Ringli, Daniel
Tonhauser, Jens
Poser, Immanuel
Breul, Jurgen
Gevensleben, Heidrun
Seifert, Hans-Helge
TI The Significance of Accurate Determination of Gleason Score for Therapeutic Options and Prognosis of Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate; Carcinoma; Gleason and combigrading; Prognosis; PSA progress; Survival
ID Prostate; Carcinoma; Gleason and combigrading; Prognosis; PSA progress; Survival
AB The Gleason score (GS) to date remains one of the most reliable prognostic predictors in prostate cancer (PCa). However, the majority of studies supporting its prognostic relevance were performed prior to its modification by the International Society of Urological Pathology (ISUP) in 2005. Furthermore, the combination of Gleason grading and nuclear/nucleolar subgrading (Helpap score) has been shown to essentially improve grading concordance between biopsy and radical prostatectomy (RP) specimens. This prompted us to investigate the modified GS and combigrading (Gleason/Helpap score) in association with clinicopathological features, biochemical recurrence (BCR), and survival. Core needle biopsies and corresponding RP specimens from 580 patients diagnosed with PCa between 2005 and 2010 were evaluated. According to the modified GS, the comparison between biopsy and RP samples resulted in an upgrading from GS 6 to GS 7a and GS 7b in 65%and 19 %, respectively. Combigrading further resulted in an upgrading from low grade (GS 6/2a) to intermediate grade PCa (GS 6/2b) in 11.1 % and from intermediate grade (GS 6/2b) to high grade PCa (GS 7b/2b) in 22.6 %. Overall, well-differentiated PCa (GS 6/2a) was detected in 2.8 % of RP specimens, while intermediate grade (GS 6/2b and GS 7a/2b) and high grade cancers (≥ GS 7b) accounted for 39.5 % and 57.4 % of cases, respectively. At a mean follow-up of 3.9 years, BCR was observed in 17.6 % of patients with intermediate (9.8 %) or high grade PCa (30.2 %), while PSA relapse did not occur in GS 6/2a PCa. In conclusion, adding nuclear/nucleolar subgrading to the modified GS allowed for a more accurate distinction between low and intermediate grade PCa, therefore offering a valuable tool for the identification of patients eligible for active surveillance (AS).
C1 [Helpap, Burkhard] Hegau-Bodensee Hospital of Singen, Department of Pathology, 78207 Singen, Germany.
[Ringli, Daniel] Hegau-Bodensee Hospital of Singen, Department of Pathology, 78207 Singen, Germany.
[Tonhauser, Jens] Hegau-Bodensee Hospital of Singen, Department of UrologySingen, Germany.
[Poser, Immanuel] Loretto Hospital, Department of Urology and Urologic OncologyFreiburg, Germany.
[Breul, Jurgen] Loretto Hospital, Department of Urology and Urologic OncologyFreiburg, Germany.
[Gevensleben, Heidrun] University of Bonn, Institute of PathologyBonn, Germany.
[Seifert, Hans-Helge] Hegau-Bodensee Hospital of Singen, Department of UrologySingen, Germany.
RP Helpap, B (reprint author), Hegau-Bodensee Hospital of Singen, Department of Pathology, 78207 Singen, Germany.
EM burkhard.helpap@hbh-kliniken.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 349
EP 356
DI 10.1007/s12253-015-0013-x
PG 8
ER
PT J
AU Kaabi, B
Belaaloui, G
Benbrahim, W
Hamizi, K
Sadelaoud, M
Toumi, W
Bounecer, H
AF Kaabi, Batoul
Belaaloui, Ghania
Benbrahim, Wassila
Hamizi, Kamel
Sadelaoud, Mourad
Toumi, Wided
Bounecer, Hocine
TI ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ADRA2A; Single nucleotide polymorphism (SNP); Breast cancer; Risk; Prognosis; Case-control study
ID ADRA2A; Single nucleotide polymorphism (SNP); Breast cancer; Risk; Prognosis; Case-control study
AB Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis.A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphismis associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphismcould represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy.
C1 [Kaabi, Batoul] Batna 1 University, Faculty of SciencesBatna, Algeria.
[Belaaloui, Ghania] Batna 2 University, Faculty of Medicine, Citee Ezzouhour, 05000 Batna, Algeria.
[Benbrahim, Wassila] Batna 2 University, Faculty of Medicine, Citee Ezzouhour, 05000 Batna, Algeria.
[Hamizi, Kamel] Batna 2 University, Faculty of Medicine, Citee Ezzouhour, 05000 Batna, Algeria.
[Sadelaoud, Mourad] LAM LaboratoryBatna, Algeria.
[Toumi, Wided] LAM LaboratoryBatna, Algeria.
[Bounecer, Hocine] Batna 2 University, Faculty of Medicine, Citee Ezzouhour, 05000 Batna, Algeria.
RP Belaaloui, G (reprint author), Batna 2 University, Faculty of Medicine, 05000 Batna, Algeria.
EM gbelaaloui@yahoo.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 357
EP 365
DI 10.1007/s12253-015-0010-0
PG 9
ER
PT J
AU Zhang, Y
Liu, P
Jiang, Y
Dou, X
Yan, J
Ma, Ch
Fan, Q
Wang, W
Su, F
Tang, H
Su, X
AF Zhang, Yafei
Liu, Peng
Jiang, Yizhen
Dou, Xiaofeng
Yan, Jianghua
Ma, Chao
Fan, Qun
Wang, Weixing
Su, Fu
Tang, Hui
Su, Xinhui
TI High Expression of Neuropilin-1 Associates with Unfavorable Clinicopathological Features in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Neuropilin-1; Expression; Clinicopathology
ID Hepatocellular carcinoma; Neuropilin-1; Expression; Clinicopathology
AB As a co-receptor for vascular endothelial growth factor (VEGF), Neuropilin-1 (NRP-1) plays an important role in angiogenesis and malignant progression of many human cancers. However, the role of NRP-1 in hepatocellular carcinoma (HCC) is not well understood. The study aimed to detected the expression of Neuropilin-1 in HCC and investigate the association between its expression and the clinicopathological characteristics and prognosis of HCC. Quantitative real-time PCR (qRT-PCR), Western blot, Immunofluorescence and immunohistochemistry (IHC) analyses were performed to characterize the expression of NRP-1 in HCC cell lines and tissues. The association of NRP-1 expression with the clinicopathological characteristics and the prognosis was subsequently assessed. qRT-PCR and Western blot assays revealed that the expression of NRP-1 in HCC was significantly increased relative to that of normal live cells and tissues (P < 0.05,and <0.001, respectively). In addition, high expression of NRP-1 was significantly associated with intrahepatic metastasis (P = 0.036), Edmondson grade (P = 0.007), TNM classification (P = 0.0031), and portal vein invasion (P = 0.004). Furthermore, the HCC patients with high NRP- 1 expression had shorter overall survival (OS), and recurrence-free survival (RFS), whereas, patients with low NRP-1 expression had better OS and RFS (P = 0.0035, and 0.0048, respectively). These data indicate that NRP-1 expression may play an important role in the progression of HCC, and that high NRP-1 expression suggests unfavorable clinicopathological characteristics and survival in HCC patients.
C1 [Zhang, Yafei] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Liu, Peng] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Jiang, Yizhen] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Dou, Xiaofeng] Zhejiang University School of Medicine, The Second Affiliated Hospital, Department of Nuclear Medicine, No.88 Jiefang Road, 310009 Hangzhou, China.
[Yan, Jianghua] Xiamen University, Medical School, Cancer Research Center, Xiangan South Road, 361102 Xiamen, China.
[Ma, Chao] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Fan, Qun] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Wang, Weixing] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Su, Fu] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Tang, Hui] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
[Su, Xinhui] Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, No.201 Hubin South Road, 361004 Xiamen, China.
RP Su, X (reprint author), Xiamen University, Zhongshan Hospital, Department of Nuclear Medicine, 361004 Xiamen, China.
EM suxinhuii@163.com
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 367
EP 375
DI 10.1007/s12253-015-0003-z
PG 9
ER
PT J
AU Fernandez-Acenero, JM
Cortes, D
Gomez del Pulgar, T
Cebrian, A
Estrada, L
Martinez-Useros, J
Celdran, A
Garcia-Foncillas, J
Pastor, C
AF Fernandez-Acenero, Jesus Maria
Cortes, Delia
Gomez del Pulgar, Teresa
Cebrian, Arancha
Estrada, Lourdes
Martinez-Useros, Javier
Celdran, Angel
Garcia-Foncillas, Jesus
Pastor, Carlos
TI PLK-1 Expression is Associated with Histopathological Response to Neoadjuvant Therapy of Hepatic Metastasis of Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatic metastasis; Colorectal carcinoma; Neoadjuvant therapy; PLK1; Histopathological response; Targeted drugs
ID Hepatic metastasis; Colorectal carcinoma; Neoadjuvant therapy; PLK1; Histopathological response; Targeted drugs
AB Polo-like kinase 1 (PLK1) is a serine/threonineprotein kinase expressed during mitosis and overexpressed in multiple human cancers, including leukemia and also many solid tumors. PLK1 knockdown has been shown to block proliferation of leukemic cell lines and the clonogenic potential of tumor cells grown from patients with cancer. PLK1 inhibition is a promising strategy for the treatment of some tumors. We aim to analyze expression of PLK1 in metastatic colorectal carcinoma. Retrospective analysis of colorectal carcinomas with hepatic metastasis during follow-up receiving neoadjuvant chemotherapy (NAC), based on oxaliplatin. Immunohistochemistry for PLK-1 in paraffin-embedded tissue from the primary and also from the metastasis. 50 patients. 32 % showed good histopathological response. 43 % of the primaries were positive for PLK1, as opposed to 23.5%of the metastasis. Expression of PLK1 was significantly reduced in metastasis compared with the primaries (p = 0.05),what could be due to therapy or to a phenotypic change of the metastatic nodule. Analysis of the prognostic influence of PLK1 expression showed significant association between PLK1 expression in metastasis and lower overall survival (p = 0.000). We have also found a significant association between PLK1 expression and histopathological response (p = 0.02). All the tumors with high expression of PLK1 showed minor response (11/11). This study shows the association between survival and poor histopathological response to therapy and high expression of PLK1 in metastasis. Our results could open a new therapeutic approach through the inhibition of PLK1.
C1 [Fernandez-Acenero, Jesus Maria] Hospital Clinico San Carlos, Department of Surgical Pathology, C/ Profesor Martin Lagos s/n, 28040 Madrid, Spain.
[Cortes, Delia] University Hospital Fundacion Jimenez Diaz, Health Research Institute FJD-UAM, Department of SurgeryMadrid, Spain.
[Gomez del Pulgar, Teresa] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Cebrian, Arancha] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Estrada, Lourdes] Hospital Clinico San Carlos, Department of Surgical Pathology, C/ Profesor Martin Lagos s/n, 28040 Madrid, Spain.
[Martinez-Useros, Javier] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Celdran, Angel] University Hospital Fundacion Jimenez Diaz, Health Research Institute FJD-UAM, Department of SurgeryMadrid, Spain.
[Garcia-Foncillas, Jesus] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Pastor, Carlos] University Hospital Fundacion Jimenez Diaz, Health Research Institute FJD-UAM, Department of SurgeryMadrid, Spain.
RP Fernandez-Acenero, JM (reprint author), Hospital Clinico San Carlos, Department of Surgical Pathology, 28040 Madrid, Spain.
EM mgg10167@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 377
EP 383
DI 10.1007/s12253-015-0015-8
PG 7
ER
PT J
AU Rakesh, N
Iyengar, A
Majumdar, K
Vidya, ShG
Shantha Kumar, SS
AF Rakesh, Nagaraju
Iyengar, Asha
Majumdar, Kuhu
Vidya, Shankar Gurram
Shantha Kumar, S S
TI Quantitative Evaluation of Tumour - Associated Tissue Eosinophilia and Cyclo-oxegenase-2 Gene in Oral Cancer Patients with Assessment of Long Term Outcomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Cyclooxygenase-2; COX-2; Tumour associated tissue eosinophilia; TATE; Locoregional recurrence
ID Oral squamous cell carcinoma; Cyclooxygenase-2; COX-2; Tumour associated tissue eosinophilia; TATE; Locoregional recurrence
AB Various histopathological parameters have been extensively studied for prognostication of oral cancer but the focus is now getting diverted towards the role of inflammatory mediators in cancer progression. The present study was undertaken to evaluate two such components of the inflammatory milieu, tumor-associated tissue eosinophilia (TATE) as well as Cyclo-oxygenase-2 (COX-2) gene expression, quantitatively in oral squamous cell carcinoma (OSCC) patients in relation to treatment outcomes and patterns of recurrence. A total of forty five patients with primary OSCC matching our inclusion criteria were selected for the study and followed up over a five year period. TATE was evaluated from the invasive front of the tumor using Haematoxylin and eosin (H & E) stained sections of histopathological specimens and graded as mild, moderate or intense. COX-2 gene expression was obtained from specimens using the reverse transcriptase - polymerase chain reaction (RT-PCR) method. A statistically significant association was observed between degree of TATE and locoregional recurrence (P < 0.001). The expression of COX-2 gene ranged from 0.4326 to 0.9998 and a highermean COX-2 score was recorded in samples with intense degree of TATE followed by moderate and mild TATE. (P < 0.001). Using the t-test, the difference in mean COX-2 was found to be statistically significant (P < 0.001) between patients who developed locoregional recurrence and those who did not. The analysis of TATE may provide an indication of future recurrence at the time of diagnosis of OSCC. Also, the increased expression of COX-2 gene in OSCC strongly suggests its possible use as a chemopreventive/chemotherapeutic target.
C1 [Rakesh, Nagaraju] M.S. Ramaiah Dental College & Hospital, Department of Oral Medicine, Diagnosis and Radiology, MSRIT Post, New BEL RoadBangalore, India.
[Iyengar, Asha] M.S. Ramaiah Dental College & Hospital, Department of Oral Medicine, Diagnosis and RadiologyBangalore, India.
[Majumdar, Kuhu] M.S. Ramaiah Dental College & Hospital, Department of Oral Medicine, Diagnosis and Radiology, MSRIT Post, New BEL RoadBangalore, India.
[Vidya, Shankar Gurram] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and MicrobiologyBangalore, India.
[Shantha Kumar, S S] M.S. Ramaiah Institute of Technology, Department of BiotechnologyBangalore, India.
RP Rakesh, N (reprint author), M.S. Ramaiah Dental College & Hospital, Department of Oral Medicine, Diagnosis and Radiology, Bangalore, India.
EM drnrakesh@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 385
EP 392
DI 10.1007/s12253-015-0016-7
PG 8
ER
PT J
AU Wang, DY
Zou, LP
Liu, XJ
Zhu, HG
Zhu, R
AF Wang, Di-Yi
Zou, Li-Ping
Liu, Xiao-Jia
Zhu, Hong-Guang
Zhu, Rong
TI Chemokine Expression Profiles of Human Hepatoma Cell Lines Mediated by Hepatitis B Virus X Protein
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatitis B virus X protein; Chemokine antibody array; Chemokines; Interleukin-8
ID Hepatitis B virus X protein; Chemokine antibody array; Chemokines; Interleukin-8
AB The hepatitis B virus X protein (HBx), which is encoded by hepatitis B virus (HBV), plays crucial roles in the tumorigenesis of HBV associated hepatocellular carcinoma (HCC). Recent studies suggest that the HBx is involved in regulation of host immune cytokines and chemokines in HBV-associated HCC patients. However, effects of the HBx on autocrine chemokine expression profiles of hepatoma cells, which were shown in modulation of tumor-immune cell interactions, have not been investigated comprehensively. In the present study, human hepatoma cell lines SMMC-7721 and HepG2 were transfected with HBx-expressing plasmid. Human chemokine antibody array 1 (RayBio®), which simultaneously detects 38 chemokine factors, was used to determine chemokine expression profiles. Real-time polymerase chain reaction (real-time PCR) was used to further confirm the differential expression of chemokines. Chemokine antibody array revealed that all 38 chomekines were found to be expressed by SMMC-7721 and HepG2 cell lines. Interleukin-8 (IL-8) was obviously up-regulated, and epithelial neutrophil-activating protein 78 (ENA78), eosinophil chemotactic protein-1 (Eotaxin-1), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3 and macrophage inflammatory protein-3β (MIP-3β) were significantly declined in both cell lines following transfection of HBx-expressing plasmid. Other chemokines showed little or no significant changes. HBx-induced differential chemokine expression levels were validated by real-time PCR. Hierarchical cluster analysis identified a distinction of chomekine expression profiles between HBX-expressing hepatoma cell lines and controls. Our findings provide new evidence that HBx is able to selectively regulate chomekines in hepatoma cells that may be involved in the regulation of tumor-immune cell interactions.
C1 [Wang, Di-Yi] Affiliated Hospital of Taishan Medical University, Department of Pathology, 271000 Taian, China.
[Zou, Li-Ping] Fudan University, Huashan Hospital, Department of Pathology, 200040 Shanghai, China.
[Liu, Xiao-Jia] Fudan University, Shanghai Medical College, Department of Oncology, 200032 Shanghai, China.
[Zhu, Hong-Guang] Fudan University, Shanghai Medical College, Department of Oncology, 200032 Shanghai, China.
[Zhu, Rong] Fudan University, Shanghai Medical College, Department of Oncology, 200032 Shanghai, China.
RP Wang, DY (reprint author), Affiliated Hospital of Taishan Medical University, Department of Pathology, 271000 Taian, China.
EM xilisa@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 393
EP 399
DI 10.1007/s12253-015-0014-9
PG 7
ER
PT J
AU Patrikidou, A
Valeri, MR
Kitikidou, K
Destouni, Ch
Vahtsevanos, K
AF Patrikidou, Anna
Valeri, Maria Rosalia
Kitikidou, Kyriaki
Destouni, Charikleia
Vahtsevanos, Konstantinos
TI Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cytology; Biomarker; Oral squamous cell carcinoma; Angiogenesis; Theranostics
ID Cytology; Biomarker; Oral squamous cell carcinoma; Angiogenesis; Theranostics
AB We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.
C1 [Patrikidou, Anna] Institute Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
[Valeri, Maria Rosalia] Theagenio Cancer Hospital, Department of CytopathologyThessaloniki, Greece.
[Kitikidou, Kyriaki] Democritus University, School of Agricultural Sciences and Forestry, Department of Forestry and Management of the Environment and Natural ResourcesAlexandroupolis, Greece.
[Destouni, Charikleia] Theagenio Cancer Hospital, Department of CytopathologyThessaloniki, Greece.
[Vahtsevanos, Konstantinos] Theagenio Cancer Hospital, Department of Oral and Maxillofacial SurgeryThessaloniki, Greece.
RP Patrikidou, A (reprint author), Institute Gustave Roussy, 94805 Villejuif, France.
EM anna.patrikidou@gustaveroussy.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 401
EP 411
DI 10.1007/s12253-015-0017-6
PG 11
ER
PT J
AU Yip, KW
He, YP
Maizaton, AA
Yusoff, S
Seow, FH
AF Yip, Kien Wai
He, Yuan Pei
Maizaton, Atmadini Abdullah
Yusoff, Suryati
Seow, Fong Heng
TI Increased Expression of Phosphatidylinositol 3-Kinase p110α and Gene Amplification of PIK3CA in Nasopharyngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PIK3CA; Akt; Nasopharyngeal carcinoma; Immunohistochemistry
ID PIK3CA; Akt; Nasopharyngeal carcinoma; Immunohistochemistry
AB Molecular alterations in PIK3CA oncogene that encodes the p110α catalytic subunit of phosphatidylinositol 3- kinase (PI3K p110α) are commonly found in human cancers. In this study, we examined the expression of PI3K p110α and PIK3CA gene amplification in 74 nasopharyngeal carcinoma (NPC) cases. Immunohistochemical staining demonstrated overexpression of PI3K p110α protein in 44.6 % (33/74) of NPCs and 4.8 % (2/42) of the adjacent normal nasopharyngeal mucosa. Copy number of PIK3CA gene was successfully analyzed in 51 of the total NPC cases and 19 non-malignant nasopharynx tissues by quantitative real-time PCR. Using mean + 2(standard deviation) of copy numbers in the non-malignant nasopharynx tissues as a cutoff value, PIK3CA copy number gain was found in 10 of 51 (19.6 %) NPC cases. High PI3K p110α expression level was correlated with increased PIK3CA copy number (Spearman’s rho =0.324, P = 0.02). PI3K p110α expression and PIK3CA copy number did not associate with Akt phosphorylation, and patient and tumor variables. This study suggests that PI3K p110α overexpression, which is attributed, at least in part, to PIK3CA gene amplification, may contribute to NPC pathogenesis. However, these molecular aberrations may not be responsible for activation of Akt signaling in NPC.
C1 [Yip, Kien Wai] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, 43400 Selangor, Malaysia.
[He, Yuan Pei] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, 43400 Selangor, Malaysia.
[Maizaton, Atmadini Abdullah] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, 43400 Selangor, Malaysia.
[Yusoff, Suryati] Hospital Kuala Lumpur, Department of PathologyKuala Lumpur, Malaysia.
[Seow, Fong Heng] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Serdang, 43400 Selangor, Malaysia.
RP Seow, FH (reprint author), Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Selangor, Malaysia.
EM shf@upm.edu.my
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 413
EP 419
DI 10.1007/s12253-015-0007-8
PG 7
ER
PT J
AU Vojkovics, D
Kellermayer, Z
Heidt, D
Mihalj, M
Kajtar, B
Ernszt, D
Kovacs, T
Nemeth, P
Balogh, P
AF Vojkovics, Dora
Kellermayer, Zoltan
Heidt, Diana
Mihalj, Martina
Kajtar, Bela
Ernszt, David
Kovacs, Tamas
Nemeth, Peter
Balogh, Peter
TI Isolation and Characterization of a Murine Spontaneous High-Grade Follicular Lymphoma with Restricted In Vivo Spreading – a Model for Lymphatic Metastasis Via the Mesentery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mouse; Follicular lymphoma; Lymphatics; Model
ID Mouse; Follicular lymphoma; Lymphatics; Model
AB Spontaneous or induced malignant lymphomas in mice are valuable tools for studying human lymphoproliferative diseases, including the mechanism of migration between peripheral lymphoid organs and positioning within distinct tissue compartments. Here we report the isolation and characterization of a novel spontaneous lymphoma from BALB/c mice showing restricted tissue distribution and metastasis. The lymphoma cells display CD19, B220, MHC II, surface IgG2a/kappa chain with VH7183 rearrangement of the IgH gene, indicating their B-cell origin. Serial intraperitoneal injection of primary tumor into both BALB/c and RAG-1- deficient hosts led to the successful propagation of lymphoma. Despite the cytological characteristics of high-grade follicular B-cell lymphoma, the tumor cells (denoted as Bc-DLFL.1) showed significantly lesser spreading to extraabdominal locations upon intraperitoneal passage compared to splenic and mesenteric lymph node expansion. In mesenteric lymph nodes the high endothelial venules contained only few tumor cells, while the lymphatic vessels were almost completely filled with lymphoma cells. Similarly, the LYVE-1-positive lymphatic capillaries within the mesentery were packed with lymphoma cells. These findings suggest that Bc-DLFL.1 cells likely propagate primarily via the lymphatic circulation within the mesentery, therefore this tumor may offer an in vivo model to investigate the tumor cell migration via the lymphatic circulation from the peritoneal cavity.
C1 [Vojkovics, Dora] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
[Kellermayer, Zoltan] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
[Heidt, Diana] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
[Mihalj, Martina] Josip Juraj Strossmayer University of Osijek, School of Medicine, Department of Physiology and ImmunologyOsijek, Croatia.
[Kajtar, Bela] University of Pecs, Department of PathologyPecs, Hungary.
[Ernszt, David] Pecsi Tudomanyegyetem, Gyogyszereszeti IntezetPecs, Hungary.
[Kovacs, Tamas] Pecsi Tudomanyegyetem, Gyogyszereszeti IntezetPecs, Hungary.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
[Balogh, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, Szigeti ut 12, H-7624 Pecs, Hungary.
RP Balogh, P (reprint author), University of Pecs, Faculty of Medicine, Department of Immunology and Biotechnology, H-7624 Pecs, Hungary.
EM balogh.peter@pte.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 421
EP 430
DI 10.1007/s12253-015-0025-6
PG 10
ER
PT J
AU Balogh, T
Lorincz, T
Stiller, I
Mandl, J
Banhegyi, G
Szarka, A
AF Balogh, Tibor
Lorincz, Tamas
Stiller, Ibolya
Mandl, Jozsef
Banhegyi, Gabor
Szarka, Andras
TI The Level of ALR is Regulated by the Quantity of Mitochondrial DNA
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Augmenter of liver regeneration; Mitochondrial DNA; ρ0 cells; Regulation
ID Augmenter of liver regeneration; Mitochondrial DNA; ρ0 cells; Regulation
AB Augmenter of liver regeneration (ALR) contributes to mitochondrial biogenesis, maintenance and to the physiological operation of mitochondria. The depletion of ALR has been widely studied and had serious consequences on the mitochondrial functions. However the inverse direction, the effect of the depletion of mitochondrial electron transfer chain and mtDNA on ALR expression has not been investigated yet. Thus mtDNA depleted, ρ0 cell line was prepared to investigate the role of mitochondrial electron transfer chain and mtDNA on ALR expression. The depletion of mtDNA has not caused any difference at mRNA level, but at protein level the expression of ALR has been markedly increased. The regulatory role of ATP and ROS levels could be ruled out because the treatment of the parental cell line with different respiratory inhibitors and uncoupling agent could not provoke any changes in the protein level of ALR. The effect of mtDNA depletion on the protein level of ALR has been proved not to be liver specific, since the phenomenon could be observed in the case of two other, non-hepatic cell lines. It seems the level of mtDNA and/or its products may have regulatory role on the protein level of ALR. The up-regulation of ALR can be a part of the adaptive response in ρ0 cells that preserves the structural integrity and the transmembrane potential despite the absence of protein components encoded by the mtDNA.
C1 [Balogh, Tibor] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
[Lorincz, Tamas] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
[Stiller, Ibolya] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1444 Budapest, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1444 Budapest, Hungary.
[Banhegyi, Gabor] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1444 Budapest, Hungary.
[Szarka, Andras] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
RP Szarka, A (reprint author), Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, 1111 Budapest, Hungary.
EM szarka@mail.bme.hu
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Ilowski M, Kleespies A, de Toni EN, Donabauer B, Jauch KW, Hengstler JG, Thasler WE, 2011, Augmenter of liver regeneration, ALR, protects human hepatocytes against apoptosis. Biochem Biophys Res Commun 404(1):148–152
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 431
EP 437
DI 10.1007/s12253-015-0020-y
PG 7
ER
PT J
AU Tian, L
Shan, W
Zhang, Y
Lv, X
Li, X
Wei, C
AF Tian, Lei
Shan, Weiyu
Zhang, Yufei
Lv, Xuejun
Li, Xuehua
Wei, Caiyun
TI Erratum to: Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Erratum to: Pathol. Oncol. Res. DOI 10.1007/s12253-015-9979-7. The original article contained an error. The name of the third author should have been Yufei Zhang not Yufei Zhnag. The corrected author name is shown above.
C1 [Tian, Lei] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
[Shan, Weiyu] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
[Zhang, Yufei] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
[Lv, Xuejun] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
[Li, Xuehua] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
[Wei, Caiyun] No. 88 Hospital of PLA, Department of Pulmonary MedicineTaian, Shandong Province, China.
RP Tian, L (reprint author), No. 88 Hospital of PLA, Department of Pulmonary Medicine, Taian, China.
EM drtianlei@163.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 439
EP 439
DI 10.1007/s12253-015-0004-y
PG 1
ER
PT J
AU Wang, Y
Wang, X
Yang, Z
Zhu, G
Chen, D
Meng, Z
AF Wang, Yongzhi
Wang, Xinghuan
Yang, Zhonghua
Zhu, Guangbin
Chen, Dong
Meng, Zhe
TI Erratum to: Menthol Inhibits the Proliferation and Motility of Prostate Cancer DU145 Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Erratum to: Pathol. Oncol. Res. (2012) 18:903–910 DOI 10.1007/s12253-012-9520-1. The original article contained an error. The corrected Acknowledgments section is shown below. Acknowledgments: This study was supported in part by grants from the National Natural Science Foundation of China (grants 81172434 and 81202027) and Fundamental Research Funds for the Central Universities (grant 2012303020211).
C1 [Wang, Yongzhi] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Wang, Xinghuan] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Yang, Zhonghua] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Zhu, Guangbin] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Chen, Dong] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
[Meng, Zhe] Wuhan University, Zhongnan Hospital, Department of Urology, Number 169, Donghu Road, 430071 Wuhan, Hubei, China.
RP Wang, X (reprint author), Wuhan University, Zhongnan Hospital, Department of Urology, 430071 Wuhan, China.
EM wangxinghuan@whu.edu.cn
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2016
VL 22
IS 2
BP 441
EP 441
DI 10.1007/s12253-012-9520-1
PG 1
ER
PT J
AU Vajaria, NB
Patel, RK
Begum, R
Patel, SP
AF Vajaria, N Bhairavi
Patel, R Kinjal
Begum, Rasheedunnisa
Patel, S Prabhudas
TI Sialylation: an Avenue to Target Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Sialic acid; Sialidase; Sialyltransferase; Sialoproteins; Sialylation
ID Sialic acid; Sialidase; Sialyltransferase; Sialoproteins; Sialylation
AB Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration.
C1 [Vajaria, N Bhairavi] The Gujarat Cancer & Research Institute, Department of Cancer Biology, Biochemistry Research Division, 380 016 Ahmedabad, Gujarat, India.
[Patel, R Kinjal] The Gujarat Cancer & Research Institute, Department of Cancer Biology, Biochemistry Research Division, 380 016 Ahmedabad, Gujarat, India.
[Begum, Rasheedunnisa] The M. S. University of Baroda, Department of BiochemistryVadodara, Gujarat, India.
[Patel, S Prabhudas] The Gujarat Cancer & Research Institute, Department of Cancer Biology, Biochemistry Research Division, 380 016 Ahmedabad, Gujarat, India.
RP Patel, SP (reprint author), The Gujarat Cancer & Research Institute, Department of Cancer Biology, Biochemistry Research Division, 380 016 Ahmedabad, India.
EM prabhudas_p@hotmail.com
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Tian Y, Estena FJ, Song J, Zhang H, 2012, Altered expression of sialylated glycoproteins in breast cancer using hydrazide chemistry and mass spectrometry. Mol Cell Proteomics 11:M111.011403
Shah MH, Telang SD, Shah PM, Patel PS, 2008, Tissue and serum alpha 2–3- and alpha 2–6-linkage specific sialylation changes in oral carcinogenesis. Glycoconj J 25:279–290
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YakobM, Fuentes L,WangMB, Abemayor E,Wong DTW(2014, Salivary biomarkers for detection of oral squamous cell carcinoma. Current state and recent advances. Curr Oral Health Rep 1:133–141
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Vajaria BN, Patel KR, Begum R, Patel JB, Shah FD, Joshi GM, Patel PS, 2014, Salivary glyco-sialylation changes monitors oral carcinogenesis. Glycoconj J 31:649–659
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Martinez-Duncker I, Salinas-Marin R, Martinez-Duncker C, 2011, Towards invivo imaging of cancer sialylation. Int J Mol Imaging 2011:283497
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Silvestri I, Testa F, Zappasodi R, CairoCW, ZhangY, Lupo B, Galli R, Nicola MD, Venerando B, Tringali C, 2014, Sialidase NEU 4 is involved in glioblastoma stem cell survival. Cell Death Dis 5:e1381
O’Shea LK, Abdulkhalek S, Allison S, Neufeld RJ, SzewczukMR, 2014, Therapeutic targeting of Neu1 sialidase with oseltamivir phosphate, Tamiflu, disables cancer cells survival in human pancreatic cancer with acquired chemoresistance. Onco Targets Ther 7: 117–134
Li X, Zhang L, Shao Y, Liang Z, Shao C, Wang B, Guo B, Li N, Zhao X, Li Y, Xu D, 2011, Effects of human plasma membrane associated sialidase siRNA on prostate cancer invasion. Biochem Biophys Res Commun 416:270–276
Tsai CS, Yen HY, Lin MI, Tsai TI, Wang SY, Huang WI, Hsu TL, Cheng YS, Fang JM, Wong CH, 2013, Cell-permeable probe for identification and imaging of human sialidases. Proc Natl Acad Sci U S A 110:2466–2471
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 443
EP 447
DI 10.1007/s12253-015-0033-6
PG 5
ER
PT J
AU Roncati, L
Barbolini, G
Piacentini, F
Piscioli, F
Pusiol, T
Maiorana, A
AF Roncati, Luca
Barbolini, Giuseppe
Piacentini, Federico
Piscioli, Francesco
Pusiol, Teresa
Maiorana, Antonio
TI Prognostic Factors for Breast Cancer: an Immunomorphological Update
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Prognostic factors; Histology; Immunohistochemistry; Tumor-infiltrating lymphocytes (TILs); Granulysin
ID Breast cancer; Prognostic factors; Histology; Immunohistochemistry; Tumor-infiltrating lymphocytes (TILs); Granulysin
AB The prognostic variability recorded within homogeneous groups of patients for anatomo-clinical disease stages has led to a more detailed biological characterization of breast cancer. Recently, the attention of the scientific community has focused on the role of tumor-infiltrating lymphocytes (TILs). Therefore, the need of an in-depth immunomorphological characterization of TILs has been emerged. The presence of TILs has been retrospectively investigated in 113 female cases of ductal carcinoma. An immunohistochemical investigation with CD3, CD4, CD8, CD20, CD56, granulysin, perforin-1, granzyme-B and TIA-1 was performed according to the standard procedures on all 17 cases with TILs evidence. TILs consisted of T and B lymphocytes: the prevalent population showed a T immunoprofile with a CD8-immunopositive killer subpopulation (Tk), close-linked to carcinomatous cells, and a CD4-immunopositive helper subpopulation (Th), inside the tumor. A time sequence (firstly T, then B) has been disclosed. Granulysin, perforin, granzyme-B and TIA-1 were expressed by Tk cells. The activated Tk cells secrete these mediators as a result of the binding to the tumor target cell, causing its lytic planned death. The cytotoxicity supported by Tk cells appears an important favorable prognostic factor. Therefore, a graduation system for TILs in breast cancer has been here proposed (absent, non-brisk, brisk).
C1 [Roncati, Luca] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
[Barbolini, Giuseppe] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
[Piacentini, Federico] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and of Public Health, Section of OncologyModena, MO, Italy.
[Piscioli, Francesco] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Pusiol, Teresa] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Maiorana, Antonio] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
RP Roncati, L (reprint author), University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, Italy.
EM emailmedical@gmail.com
CR World Health Organization. International Agency for Research on Cancer, 2014, Breast cancer. Chapter 5.2. In:World Cancer Report 362–373
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 449
EP 452
DI 10.1007/s12253-015-0024-7
PG 4
ER
PT J
AU Zhao, J
Chen, J
Lin, H
Jin, R
Liu, J
Liu, X
Meng, N
Cai, X
AF Zhao, Jie
Chen, Jiang
Lin, Hui
Jin, Renan
Liu, Jinghua
Liu, Xiaolong
Meng, Ning
Cai, Xiujun
TI The Clinicopathologic Significance of BAF250a (ARID1A) Expression in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; ARID1A; BAF250a; Tumor suppressor gene
ID Hepatocellular carcinoma; ARID1A; BAF250a; Tumor suppressor gene
AB Hepatocellular carcinoma (HCC) is one of the most common and lethal human cancers. Recently, exome sequencing has revealed that mutation of ARID1A is frequent in HCC. Herein, we determined the clinicopathologic significance of ARID1A expression in HCC.We detected the level of mRNA and protein expression of ARID1A in 12 paired HCC tumors and adjacent non-cancerous tissues by quantitative real-time PCR and immunohistochemistry (IHC). In addition, we determined the expression of BAF250a on 121 HCC tumors by IHC and assessed the association between BAF250a expression and clinicopathologic and prognostic features. The levels of ARID1A mRNA were significantly elevated in 10 of 12 HCC tumors compared with adjacent non-cancerous tissues. The level of BAF250a protein expression was higher in 10 of 12 HCC tumors compared with adjacent liver tissues. IHC indicated that 12.17 % of HCC tumors (14/115) were BAF250a-negative. Loss of BAF250a was significantly associated with larger tumor size, but not associated with other clinicopathologic features. There was no significant difference in disease-free or overall survival between BAF250a-positive and BAF250a-negative patients. Most HCCs had an increased level of ARID1A mRNA and BAF250a expression. Loss of BAF250a was significantly more frequent in larger HCC tumors, but had no prognostic significance.
C1 [Zhao, Jie] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Chen, Jiang] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Lin, Hui] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Jin, Renan] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Liu, Jinghua] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Liu, Xiaolong] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Meng, Ning] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
[Cai, Xiujun] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, No. 3, East Qinchun Road, 310016 Hangzhou, China.
RP Cai, X (reprint author), Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hepatobiliary and Pancreas Surgery, 310016 Hangzhou, China.
EM cxjsrrsh@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 453
EP 459
DI 10.1007/s12253-015-0022-9
PG 7
ER
PT J
AU El-Gendi, MS
Mostafa, FM
AF El-Gendi, Mohamed Saba
Mostafa, Farouk Mohamed
TI Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Runx2; Breast carcinoma; Prognostic factor; Clinical outcome; Survival
ID Runx2; Breast carcinoma; Prognostic factor; Clinical outcome; Survival
AB The Runx family of transcription factors has been implicated in cancer progression, both positively and negatively. Recent studies assigned a role for Runx2 in promoting breast cancer metastasis. However, the role of Runx2 during the early stage of breast carcinoma and its association with clinical outcomes remain unknown. Assessing the clinicopathological significance of Runx2 expression in a cohort of breast invasive ductal carcinomas (IDC). The correlation of nuclear Runx2 LI with clinicopathological parameters was assessed in 84 IDCs. To study the association of Runx2 with patient outcomes, in addition to treating it as a continuous variable, Runx2 was categorized by its median value (65) and by an additional two cut-off points determined by ROC curve analyses, at 45 for disease free survival (DFS) and 40 for overall survival (OS). Multivariate Cox regression models were also constructed. We used the best subset regression to identify models that predict DFS and OS with as few predictors as possible, and validation was performed. Based on the "Predicted R2", the three best models were identified. Using Cox-regression, the interaction between Runx2 and other clinicopathological terms was tested. Runx2 LI was significantly associated only with positive Her-2 status, and did not correlate significantly with other clinicopathological parameters. Although Runx2 LI, in the continuous form and when categorized by the median, did not correlate significantly with DFS and OS; after it was categorized using the optimal cutoff points determined using ROC curve analysis, the patients with Runx2 LI >45%showed a significantly higher event rate and shorter DFS (P = 0.047), whereas patients with Runx2 LI >40 % showed a significantly shorter OS (P = 0.050). Moreover, Runx2 LI contributed significantly in the models built to predict DFS and OS. For DFS, no interaction terms contributed significantly to the models. However, among stage IV cases, the interaction term between centred Runx2 and ER significantly contributed to the prediction of OS. Runx2 was a significant predictor of OS in this model. Runx2 has a role in biological behaviour and affects the outcome of IDC; therefore, its inhibition may be a new therapeutic strategy. The predictability of Runx2 for OS in stage IV tumours differs with different ER states. The pattern of this difference was not determined because the sample size was not sufficient to allow pattern testing.
C1 [El-Gendi, Mohamed Saba] University of Alexandria, Faculty of Medicine, Department of PathologyAlexandria, Egypt.
[Mostafa, Farouk Mohamed] Alexandria Faculty of Medicine, Department of Clinical Oncology and Nuclear MedicineAlexandria, Egypt.
RP El-Gendi, MS (reprint author), University of Alexandria, Faculty of Medicine, Department of Pathology, Alexandria, Egypt.
EM sabaelgendi@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 461
EP 470
DI 10.1007/s12253-015-0018-5
PG 10
ER
PT J
AU Wu, X
Sun, L
Wang, X
Su, P
Li, Z
Zhang, Ch
Wang, Y
Gao, P
Ma, R
AF Wu, Xiaojuan
Sun, Limin
Wang, Xiao
Su, Peng
Li, Zhishuang
Zhang, Chunyan
Wang, Yan
Gao, Peng
Ma, Rong
TI Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mPRα; p-Akt; MMP-9; Invasive breast cancer; Metastasis
ID mPRα; p-Akt; MMP-9; Invasive breast cancer; Metastasis
AB Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPRα and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptorα (mPRα) was investigated. The results showed that the protein expression of mPRα, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPRα and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPRα and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPRα and p-Akt together with MMP-9. The results confirm that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPRα signaling pathway.
C1 [Wu, Xiaojuan] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Sun, Limin] Shandong Jiaotong Hospital, Department of OrthopedicsJinan, Shandong, China.
[Wang, Xiao] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Su, Peng] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Li, Zhishuang] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Zhang, Chunyan] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Wang, Yan] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Gao, Peng] The Second Hospital of Shandong University, Department of Pathology, 44 Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Ma, Rong] Shandong Univeristy, QiLu Hospital, Department of Breast SurgeryJinan, Shandong, China.
RP Gao, P (reprint author), The Second Hospital of Shandong University, Department of Pathology, 250012 Jinan, China.
EM gaopeng@sdu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 471
EP 476
DI 10.1007/s12253-015-0023-8
PG 6
ER
PT J
AU Zheng, DS
Bui, K
Chiappori, A
Bepler, G
Bui, MM
AF Zheng, D Sam
Bui, Katherine
Chiappori, Alberto
Bepler, Gerold
Bui, M Marilyn
TI RRM1, ERCC1 and TS1 Immunofluorescence Expression in Leiomyosarcoma: A Tissue Microarray Study with Clinical Outcome Correlation Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Soft tissue tumor; Leiomyosarcoma; Prognosis; Survival; Tissue microarray; ERCC1; RRM1; TS1
ID Soft tissue tumor; Leiomyosarcoma; Prognosis; Survival; Tissue microarray; ERCC1; RRM1; TS1
AB ERCC1, RRM1 and TS1 are reportedly linked to chemotherapy resistance in lung and other cancers. However, there are currently no studies reporting the relationship between these genes and clinical parameters in leiomyosarcomas. Method: This study investigated the expression pattern of ERCC1, RRM1 and TS1 in forty-four leiomyosarcoma samples by the use of tissue microarray (TMA), immunofluorescence and AQUA methods. The results were then analyzed for expression level and correlations were made with clinical outcome to determine their potential prognostic value in leiomyosarcoma. Results: In the forty-four samples studied, the expression level of these three proteins can be well quantified in the AQUA system and reflected by the AQUA score. RRM1 and ERCC1 expression levels did not show any relationship with overall survival. However, a correlation was found between TS1 expression in the cytoplasm and overall survival. The high expression group had a shorter overall survival time (log-rank p = 0.0498). This trend was confirmed by the Cox proportional hazards model. Discussion: The poor overall survival of leiomyosarcoma is linked to TS1 cytoplasm expression which may be useful in predicting prognoses of this tumor, methods targeting expression of TS1 may lead to improved overall survival in leiomyosarcoma, though more detailed information regarding treatment information and a larger sample size is needed to confirm this phenomenon.
C1 [Zheng, D Sam] University of South Florida, College of MedicineTampa, FL, USA.
[Bui, Katherine] University of South Florida, College of MedicineTampa, FL, USA.
[Chiappori, Alberto] H. Lee Moffitt Cancer Center, Thoracic Oncology, MCC 2nd FL, 12029 Magnolia Drive, 33647 Tampa, FL, USA.
[Bepler, Gerold] Detroit Medical Center, Barbara Ann Karmanos Cancer InstituteDetroit, MI, USA.
[Bui, M Marilyn] H. Lee Moffitt Cancer Center, Thoracic Oncology, MCC 2nd FL, 12029 Magnolia Drive, 33647 Tampa, FL, USA.
RP Bui, MM (reprint author), H. Lee Moffitt Cancer Center, Thoracic Oncology, 33647 Tampa, USA.
EM marilyn.bui@moffitt.org
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 477
EP 482
DI 10.1007/s12253-015-0021-x
PG 6
ER
PT J
AU Liu, L
Yang, ZL
Wang, Ch
Miao, X
Liu, Z
Li, D
Zou, Q
Li, J
Liang, L
Zeng, G
Chen, S
AF Liu, Luyao
Yang, Zhu-Lin
Wang, Chunwei
Miao, Xiongying
Liu, Zhiyu
Li, Daiqiang
Zou, Qiong
Li, Jinghe
Liang, Lufeng
Zeng, Guixiang
Chen, Senlin
TI The Expression of Notch 1 and Notch 3 in Gallbladder Cancer and Their Clinicopathological Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder cancer; Prognosis; Notch 1; Notch 3; Adenocarcinoma; Squamous cell/adenosquamous carcinomas
ID Gallbladder cancer; Prognosis; Notch 1; Notch 3; Adenocarcinoma; Squamous cell/adenosquamous carcinomas
AB Gallbladder cancers (GBCs) are highly malignant gastrointestinal cancers. The biological makers for the prognosis and targeting therapy of GBCs have not been established. The protein expression of Notch 1 and Notch 3 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (AC) was measured using immunohistochemistry. Positive Notch 1 and Notch 3 expression in both SC/ASC and AC was significantly associated with large tumor size, invasion, metastasis, and low surgical curability (P < 0.05 or P < 0.01). Univariate Kaplan-Meier analysis showed that positive Notch 1 and Notch 3 expression was significantly associated with mean survival of SC/ASC and AC patients (P < 0.01 or P < 0.001). Multivariate Cox regression analysis showed that positive Notch 1 and Notch 3 expression, as well as low differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Positive Notch 1 and Notch 3 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in both SC/ASC and AC patients.
C1 [Liu, Luyao] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Yang, Zhu-Lin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Wang, Chunwei] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Miao, Xiongying] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Liu, Zhiyu] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, Hunan, China.
[Li, Daiqiang] Central South University, Second Xiangya Hospital, Department of Pathology, 410011 Changsha, Hunan, China.
[Zou, Qiong] Central South University, Third Xiangya Hospital, Department of Pathology, 410013 Changsha, Hunan, China.
[Li, Jinghe] Central South University, Xiangya Basic Medical College, Department of Pathology, 410078 Changsha, Hunan, China.
[Liang, Lufeng] Hunan Provincial People’s Hospital, Department of Hepatobiliary and Pancreatic Surgery, 410007 Changsha, Hunan, China.
[Zeng, Guixiang] Loudi Central Hospital, Department of Pathology, 417011 Loudi, Hunan, China.
[Chen, Senlin] Hunan Provincial Tumor Hospital, Department of Pathology, 410013 Changsha, Hunan, China.
RP Yang, ZL (reprint author), Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary Diseases, 410011 Changsha, China.
EM zhulinyang@yahoo.com
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Ding XY, Ding J,Wu K, et al., 2012, Cross-talk between endothelial cells and tumor via delta-like ligand 4/notch/PTEN signaling inhibits lung cancer growth. Oncogene 31:2899–2906
Liu DC, Yang ZL, 2011, Clinicopathologic significance of minichromosomemaintenance protein 2 and Tat-interacting protein 30 expression in benign and malignant lesions of the gallbladder. Hum Pathol 42:1676–1683
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Howard JD, Moriarty WF, Park J, et al., 2013, Notch signaling mediatesmelanoma-endothelial cell communication andmelanoma cell migration. Pigment Cell Melanoma Res 26:697–707
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 483
EP 492
DI 10.1007/s12253-015-0019-4
PG 10
ER
PT J
AU Lakosi, F
Gulyban,
Simoni, BMS
Nguyen, VP
Cucchiaro, S
Seidel, L
Janvary, ZsL
Nicolas, S
Vavassis, P
Coucke, P
AF Lakosi, Ferenc
Gulyban, Akos
Simoni, Ben-Mustapha Selma
Nguyen, Viet Paul
Cucchiaro, Severine
Seidel, Laurence
Janvary, Zsolt Levente
Nicolas, Sophie
Vavassis, Peter
Coucke, Philippe
TI The Influence of Treatment Position (Prone vs. Supine) on Clip Displacement, Seroma, Tumor Bed and Partial Breast Target Volumes: Comparative Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Prone breast radiotherapy; Partial breast irradiation; Target volume
ID Breast cancer; Prone breast radiotherapy; Partial breast irradiation; Target volume
AB To analyse the displacement of surgical clips in prone (Pr) position and assess the consequences on target volumes and integral dose of partial breast irradiation (PBI). 30 post-lumpectomy breast cancer patients underwent CT imaging in supine (Su) and Pr. Clip displacements were measured by the distances from the clips to a common fix bony reference point. On each dataset, the tumour bed (TB = clips ± seroma), clinical target volume (CTV = TB + 1.5 cm) and planning target volumes (PTV = CTV + 1 cm) for PBI were determined and the volume pairs were compared. Furthermore estimation of integral dose ratio (IDR) within the breast from tangential treatment was performed as the ratio of the irradiated breast volume and the volume encompassing all clips. Clips close to the chest wall (CW) in Su showed significantly less displacement in Pr. The mean volumes of seroma, CTV and PTV were significantly higher in Pr than in Su. The PTV volume difference (Pr-Su) was significantly higher in patients with presence of seroma, deep clips and TB location in the superior-internal-quadrant (SIQ) and at the junction of superior quadrants (jSQ). In a multivariate analysis two factors remained significant: seroma and TB localization in SIQjSQ. The IDR was significantly larger in Su than in Pr (7.6 vs. 4.1 p <0.01). Clip displacements varied considerably with respect to their relative position to the CW. In selected patients Pr position potentially leads to a significant increase in target volumes of PBI. Tangential beam arrangement for PBI should be avoided, not only in Su but in Pr as well in case of clipbased target volume definition.
C1 [Lakosi, Ferenc] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Gulyban, Akos] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Simoni, Ben-Mustapha Selma] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Nguyen, Viet Paul] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Cucchiaro, Severine] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Seidel, Laurence] University Hospital of Liege, Department of BiostatisticsLiege, Belgium.
[Janvary, Zsolt Levente] University of Debrecen, Medical and Health Science Center, Institute of Nuclear MedicineDebrecen, Hungary.
[Nicolas, Sophie] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
[Vavassis, Peter] Hopital Maisonneuve-Rosemont, Department of Radiation OncologyMontreal, Quebec, Canada.
[Coucke, Philippe] University Hospital of Liege, Department of Radiation Oncology, B.35, B-4000 Liege, Belgium.
RP Lakosi, F (reprint author), University Hospital of Liege, Department of Radiation Oncology, B-4000 Liege, Belgium.
EM lakosiferenc@yahoo.com
CR Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M et al, 2011, Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716., DOI 10.1016/S0140-6736(11)61629-2
Kovacs A, Lakosi F, Liposits G, Toller G, Hadjiev J, Vandulek C et al, 2011, 3-D conformal photon boost in the treatment of early stage breast cancer: four year follow up results. Pathol Oncol Res 17:17– 23., DOI 10.1007/s12253-010-9264-8
Polgar C, Van Limbergen E, Potter R, Kovacs G, Polo A, Lyczek J et al, 2010, Patient selection for accelerated partial-breast irradiation, APBI, after breast-conserving surgery: recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology, GEC-ESTRO, breast cancer working group ba. Radiother Oncol 94:264–273., DOI 10.1016/j. radonc.2010.01.014
Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH et al, 2009, Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology, ASTRO). Int J Radiat Oncol Biol Phys 74:987–1001., DOI 10.1016/j.ijrobp.2009.02.031
Polgar C, Fodor J, Major T, Sulyok Z, Kasler M, 2013, Breastconserving therapy with partial or whole breast irradiation: tenyear results of the Budapest randomized trial. Radiother Oncol 108:197–202., DOI 10.1016/j.radonc.2013.05.008
Mozsa E, Meszaros N,Major T, Frohlich G, Stelczer G, Sulyok Z et al, 2014, Accelerated partial breast irradiation with external beam three-dimensional conformal radiotherapy : five-year results of a prospective phase II clinical study. Strahlenther Onkol 444–450., DOI 10.1007/s00066-014-0633-1
Formenti SC, Hsu H, Fenton-Kerimian M, Roses D, Guth A, Jozsef G et al, 2012, Prone accelerated partial breast irradiation after breast-conserving surgery: five-year results of 100 patients. Int J Radiat Oncol Biol Phys., DOI 10.1016/j.ijrobp.2012.01.039
Kirby AM, Evans PM, Donovan EM, Convery HM, Haviland JS, Yarnold JR, 2010, Prone versus supine positioning for whole and partial-breast radiotherapy: a comparison of non-target tissue dosimetry. Radiother Oncol 96:178–184., DOI 10.1016/j.radonc.2010. 05.014
Coles CE, Wilson CB, Cumming J, Benson JR, Forouhi P, Wilkinson JS et al, 2009, Titaniumclip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group. Eur J Surg Oncol 35:578–582., DOI 10.1016/j.ejso.2008.09.005
Major T, Frohlich G, Lovey K, Fodor J, Polgar C, 2009, Dosimetric experience with accelerated partial breast irradiation using imageguided interstitial brachytherapy. Radiother Oncol 90:48–55., DOI 10.1016/j.radonc.2007.10.027
Ahunbay EE, Robbins J, Christian R, Godley A, White J, Li XA, 2012, Interfractional target variations for partial breast irradiation. Int J Radiat Oncol Biol Phys 82:1594–1604., DOI 10.1016/j.ijrobp. 2011.01.041
Kirby AM, Evans PM, Helyer SJ, Donovan EM, Convery HM, Yarnold JR, 2011, A randomised trial of supine versus prone breast radiotherapy, SuPr study): comparing set-up errors and respiratory motion. Radiother Oncol 100:221–226., DOI 10.1016/j.radonc.2010. 11.005
Mitchell J, Formenti SC, DeWyngaert JK, 2010, Interfraction and intrafraction setup variability for prone breast radiation therapy. Int J Radiat Oncol Biol Phys 76:1571–1577., DOI 10.1016/j.ijrobp. 2009.07.1683
Lakosi F, Gulyban A, Janvary L, Simoni SB-M, Jansen N, Seidel L et al, 2015, Respiratory motion, anterior heart displacement and heart dosimetry: comparison between prone, Pr, and supine, Su, whole breast irradiation. Pathol Oncol Res., DOI 10.1007/s12253-
-9932-9 15. MukeshM, Harris E, Jena R, Evans P, Coles C, 2012, Relationship between irradiated breast volume and late normal tissue complications: a systematic review. Radiother Oncol 104:1–10., DOI 10.1016/ j.radonc.2012.04.025
Leonard KL, Hepel JT, Hiatt JR, Dipetrillo TA, Price LL,Wazer DE, 2013, The effect of dose-volume parameters and interfraction interval on cosmetic outcome and toxicity after 3-dimensional conformal accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 85:623–629., DOI 10.1016/j.ijrobp.2012.06.052
Formenti SC, DeWyngaert JK, Jozsef G, Goldberg JD, 2012, Prone vs supine positioning for breast cancer radiotherapy. JAMA 308: 861–863., DOI 10.1001/2012.jama.10759
Mulliez T, Speleers B, Madani I, De Gersem W, Veldeman L, De Neve W, 2013, Whole breast radiotherapy in prone and supine position: is there a place for multi-beam IMRT? Radiat Oncol 8: 151., DOI 10.1186/1748-717X-8-151
Qiu J-J, Chang Z, Horton JK, Wu Q-RJ, Yoo S, Yin F-F, 2014, Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation, APBI). Med Dosim 39:152–158., DOI 10.1016/j.meddos.2013.12.001
Fahimian B, Yu V, Horst K, Xing L, Hristov D, 2013, Trajectory modulated prone breast irradiation: a LINAC-based technique combining intensity modulated delivery and motion of the couch. Radiother Oncol 109:475–481., DOI 10.1016/j.radonc.2013.10.031
Vicini F, Winter K, Wong J, Pass H, Rabinovitch R, Chafe S et al, 2010, Initial efficacy results of RTOG 0319: three-dimensional conformal radiation therapy, 3D-CRT, confined to the region of the lumpectomy cavity for stage I/ II breast carcinoma. Int J Radiat Oncol Biol Phys 77:1120–1127., DOI 10.1016/j.ijrobp.2009.06.067
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 493
EP 500
DI 10.1007/s12253-015-0028-3
PG 8
ER
PT J
AU Hashiguchi, Y
Kasai, M
Fukuda, T
Ichimura, T
Yasui, T
Sumi, T
AF Hashiguchi, Yasunori
Kasai, Mari
Fukuda, Takeshi
Ichimura, Tomoyuki
Yasui, Tomoyo
Sumi, Toshiyuki
TI Serum Sialyl-Tn (STN) as a Tumor Marker in Patients with Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serum sialyl Tn level; Endometrial cancer; Tumormarker
ID Serum sialyl Tn level; Endometrial cancer; Tumormarker
AB There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60 years (28–83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44 months (1–83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p =0.02) and lymph node metastasis (p= 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer.
C1 [Hashiguchi, Yasunori] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
[Kasai, Mari] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
[Fukuda, Takeshi] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
[Ichimura, Tomoyuki] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
[Yasui, Tomoyo] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
[Sumi, Toshiyuki] Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 1-4-3 Asahimachi, Abeno-ku, 545-8585 Osaka, Japan.
RP Hashiguchi, Y (reprint author), Osaka City University, Graduate School of Medicine, Department of Obstetrics and Gynecology, 545-8585 Osaka, Japan.
EM cbl37090yh@nifty.com
CR Staff AC, Trovik J, Eriksson AGZ et al, 2011, Elevated plasma growth differentiation factor-15 correlates with lymph node metastases and poor survival in endometrial cancer. Clin Cancer Res 17(14):4825–4833
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Ohno S, Ohno Y, Nakada H et al, 2006, Expression of Tn and sialyl-Tn antigen in endometrial cancer: its relationship with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patient prognosis. Anticancer Res 26:4047–4053
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 501
EP 504
DI 10.1007/s12253-015-0030-9
PG 4
ER
PT J
AU Nagy, BZs
Wichmann, B
Kalmar, A
Bartak, KB
Tulassay, Zs
Molnar, B
AF Nagy, Brigitta Zsofia
Wichmann, Barnabas
Kalmar, Alexandra
Bartak, Kinga Barbara
Tulassay, Zsolt
Molnar, Bela
TI miRNA Isolation from FFPET Specimen: A Technical Comparison of miRNA and Total RNA Isolation Methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MiRNA; Isolation kit; Comparison; Reference MiRNA; U6; Normalization; Total RNA; Isolation; Ffpe; Colon; Colorectal cancer; Concentration
ID MiRNA; Isolation kit; Comparison; Reference MiRNA; U6; Normalization; Total RNA; Isolation; Ffpe; Colon; Colorectal cancer; Concentration
AB MiRNA remain stable for detection and PCR-based amplification in FFPE tissue samples. Several miRNA extraction kits are available, however miRNA fraction, as part of total RNA can be isolated using total RNA purification methods, as well. Our primary aim was to compare four different miRNA and total RNA isolation methods from FFPE tissues. Further purposes were to evaluate quantitatively and qualitatively the yield of the isolated miRNA. MiRNAs were isolated from normal colorectal cancer FFPE specimens from the same patients. Two miRNA isolation kits (High Pure miRNA Isolation Kit, miRCURY™ RNA Isolation Kit) and two total RNA isolation kits were compared (High Pure RNA Paraffin Kit, MagNA Pure 96 Cellular RNA LV Kit). Quantity and quality were determined, expression analysis was performed by realtime PCR using qPCR Human Panel I + II (Exiqon) method detecting 742 human miRNAs in parallel. The yield of total RNA was found to be higher than miRNA purification protocols (in CRC: Ex: 0203 ± 0021 μg; HPm: 1,45 ± 0,8 μg; HPp: 21,36 ± 4,98 μg; MP: 8, 6 ± 5,1 μg). MiRNAs were detected in lower relative quantity of total RNA compared to the miRNA kits. Higher number of miRNAs could be detected by the miRNA isolation kits in comparison to the total RNA isolation methods. (Ex: 497 ± 16; HPm: 542 ± 11; HPp: 332 ± 36; MP: 295 ± 74). Colon specific miRNAs (miR-21-5p;-34-5p) give satisfying results by miRNA isolation kits. Although miRNA can be detected also after total RNA isolation methods, for reliable and reproducible miRNA expression profiling the use of miRNA isolation kits are more suitable.
C1 [Nagy, Brigitta Zsofia] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Str. 46, 1088 Budapest, Hungary.
[Wichmann, Barnabas] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Str. 46, 1088 Budapest, Hungary.
[Bartak, Kinga Barbara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Str. 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Str. 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi Str. 46, 1088 Budapest, Hungary.
RP Nagy, BZs (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM nagyzsofiab@gmail.com
CR Lewis BP, Burge CB, Bartel DP, 2005, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20., DOI 10.1016/j. cell.2004.12.035
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Oue N, Anami K, Schetter AJ, Moehler M, Okayama H, KhanMA, Bowman ED, Mueller A, Schad A, ShimomuraM, Hinoi T, Aoyagi K, Sasaki H, Okajima M, Ohdan H, Galle PR, YasuiW, Harris CC, 2014, High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer. Int J Cancer 134(8):1926–1934., DOI 10.1002/Ijc.28522
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 505
EP 513
DI 10.1007/s12253-015-0027-4
PG 9
ER
PT J
AU Erol, O
Suren, D
Tutus, B
Toptas, T
Gokay, AA
Derbent, UA
Ozel, KM
Sezer, C
AF Erol, Onur
Suren, Dinc
Tutus, Birsel
Toptas, Tayfun
Gokay, Arda Ahmet
Derbent, Uysal Aysel
Ozel, Kemal Mustafa
Sezer, Cem
TI Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE E-cadherin; p53; Inhibin-α; Hydatidiform mole
ID E-cadherin; p53; Inhibin-α; Hydatidiform mole
AB The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n=23), PHM (n= 24), and CHM (n=23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.
C1 [Erol, Onur] Antalya Training and Research Hospital, Department of Obstetrics and GynecologyAntalya, Turkey.
[Suren, Dinc] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Tutus, Birsel] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Toptas, Tayfun] Antalya Training and Research Hospital, Department of Gynecologic OncologyAntalya, Turkey.
[Gokay, Arda Ahmet] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Derbent, Uysal Aysel] Antalya Training and Research Hospital, Department of Obstetrics and GynecologyAntalya, Turkey.
[Ozel, Kemal Mustafa] Antalya Training and Research Hospital, Department of Obstetrics and GynecologyAntalya, Turkey.
[Sezer, Cem] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
RP Erol, O (reprint author), Antalya Training and Research Hospital, Department of Obstetrics and Gynecology, Antalya, Turkey.
EM dronurerol@hotmail.com
CR Cheung AN, 2003, Pathology of gestational trophoblastic disease. Baillieres Best Pract Res Clin Obstet Gynaecol 17:849–868
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Jun SY, Ro JY, Kim KR, 2003, P57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles. Histopathology 43:17–25
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Floridon C, Nielsen O, Holund B, Sunde L, Westergaard JG, Thomsen SG, Teisner B, 2000, Localization of E-cadherin in villous, extravillous and vascular trophoblasts during intrauterine, ectopic and molar pregnancy. Mol Hum Reprod 6:943–950
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Batistatou A, Makrydimas G, Zagorianakou N, Zagorianakou P, Nakanishi Y, Agnantis NJ, Hirohashi S, Charalabopoulos K, 2007, Expression of dysadherin and E-cadherin in trophoblastic tissue in normal and abnormal pregnancies. Placenta 28:590–592
Shu H, Chen H, Yang B, Chang Z, Xiong M, Chen W, 2013, Aberrant expression of E-cadherin and integrin β-1 in trophoblasts is associated with malignant gestational trophoblastic diseases. Int J Gynecol Cancer 23:749–754
Xue WC, Feng HC, Tsao SW, Chan KY, Ngan HY, Chiu PM, Maccalman CD, CheungAN, 2003, Methylation status and expression of E-cadherin and cadherin-11 in gestational trophoblastic diseases. Int J Gynecol Cancer 13:879–888
Balaram P, Alex S, Panikkar B, Rajalekshmi TN, 2004, Adhesionrelated proteins E-cadherin, P-cadherin, CD44, and CD44v6, and antimetastatic protein nm23H1 in complete hydatidiform moles in relation to invasion potential. Int J Gynecol Cancer 14:532–539
Cohen M, Meisser A, Haenggeli L, Irminger-Finger I, Bischof P, 2007, Status of p53 in first-trimester cytotrophoblastic cells. Mol Hum Reprod 13:111–116
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de Kretser DM, HedgerMP LKL, Phillips DJ, 2002, Inhibins, activins and follistatin in reproduction. Hum Reprod Update 8: 529–541
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 515
EP 521
DI 10.1007/s12253-015-0031-8
PG 7
ER
PT J
AU Nemejcova, K
Ticha, I
Kleiblova, P
Bartu, M
Cibula, D
Jirsova, K
Dundr, P
AF Nemejcova, Kristyna
Ticha, Ivana
Kleiblova, Petra
Bartu, Michaela
Cibula, David
Jirsova, Katerina
Dundr, Pavel
TI Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clear cell carcinoma; Endometrioid carcinoma; HNF-1-beta; Immunohistochemistry; Mutation analysis; Methylation
ID Clear cell carcinoma; Endometrioid carcinoma; HNF-1-beta; Immunohistochemistry; Mutation analysis; Methylation
AB Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88% of hyperplasias with atypias (14/16 cases), 91 %of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expressionwasmostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation.
C1 [Nemejcova, Kristyna] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 2 12800 Prague, Czech Republic.
[Ticha, Ivana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 2 12800 Prague, Czech Republic.
[Kleiblova, Petra] Charles University in Prague, First Faculty of Medicine, General University Hospital, Institute of Biochemistry and Experimental OncologyPrague, Czech Republic.
[Bartu, Michaela] Charles University, 1st Faculty of Medicine and General Teaching HospitalPrague, Czech Republic.
[Cibula, David] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
[Jirsova, Katerina] Charles University in Prague, First Faculty of Medicine, Bank of Biological MaterialPrague, Czech Republic.
[Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 2 12800 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 2 12800 Prague, Czech Republic.
EM pdundr@seznam.cz
CR Barbacci E, Chalkiadaki A, Masdeu C, et al., 2004, HNF1β/TCF2 mutations impair transactivation potential through altered coregulator recruitment. Hum Mol Genet 13:3139–3149
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Yamamoto S, Tsuda H, Aida S, Shimazaki H, Tamai S, Matsubara O, 2007, Immunohistochemical detection of hepatocyte nuclear factor 1β in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium. Hum Pathol 38:1074–1080
Kato N, Sasou S, Motoyama T, 2006, Expression of hepatocyte nuclear factor-1β, HNF-1β, in clear cell tumors and endometriosis of the ovary. Mod Pathol 19:83–89
Kato N, Tamura G, Motoyama T, 2008, Hypomethylation of hepatocyte nuclear factor-1β, HNF-1β, CpG island in clear cell carcinoma of the ovary. Virchows Arch 452:175–180
Park KJ, Kiyokawa T, Soslow RA, Lamb CA, Oliva E, Zivanovic O, JuretzkaMM, Pirog EC, 2011, Unusual endocervical adenocarcinomas: an immunohistochemical analysis with molecular detection of human papillomavirus. Am J Surg Pathol 35:633–646., DOI 10.1097/PAS.0b013e31821534b9
Kenny SL, McBride HA, Jamison J, McCluggage WG, 2012, Mesonephric adenocarcinomas of the uterine cervix and corpus: HPV-negative neoplasms that are commonly PAX8, CA125, and HMGA2 positive and that may be immunoreactive with TTF1 and hepatocyte nuclear factor 1-β. Am J Surg Pathol 36:799–807., DOI 10.1097/PAS.0b013e31824a72c6
Fadare O, Liang SX, 2012, Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma. Appl Immunohistochem Mol Morphol 20:580–587., DOI 10.1097/ PAI.0b013e31824973d1
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Fadare O, Zhao C, Khabele D, et al., 2015, Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase, AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours. Pathology 47:105–111., DOI 10.1097/PAT. 0000000000000223
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 523
EP 530
DI 10.1007/s12253-015-0037-2
PG 8
ER
PT J
AU Shen, X
Guo, Y
Qi, J
Shi, W
Wu, X
Ni, H
Ju, Sh
AF Shen, Xianjuan
Guo, Yuehua
Qi, Jing
Shi, Wei
Wu, Xinhua
Ni, Hongbing
Ju, Shaoqing
TI Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bcell-activating factor (BAFF); Drug resistance; Multiple myeloma (MM); microRNA; Signaling pathway
ID Bcell-activating factor (BAFF); Drug resistance; Multiple myeloma (MM); microRNA; Signaling pathway
AB An increasing amount of experimental evidence has shown that miRNAs play a causal role in hematologic tumorigenesis. In this study, we characterized the role of miR-202 in multiple myeloma (MM) drug sensitivity. The potential binding site of miR-202 and B cell-activating factor (BAFF) was confirmed by luciferase reporter assay. MM cells were transfected with miR-202 mimics and inhibitor. Cells growth was measured by WST-1 cell proliferation assay and Annexin V-FLUOS apoptosis assay. BAFF and miR-202 mRNA levels were measured by real-time PCR. Meanwhile, BAFF, Bcl-2 family survival proteins and MAPK pathway proteins were measured by Western blot. It was found that miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNK/SAPK signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells. These results suggest that the regulatory mechanism of miR-202 expression may be a promising target for fine-tuning anti-myeloma therapy.
C1 [Shen, Xianjuan] Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, #20 Xisi Road, 226001 Nantong, JS, China.
[Guo, Yuehua] Nantong University, #9 Seyuan Road, 226001 Nantong, JS, China.
[Qi, Jing] Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, #20 Xisi Road, 226001 Nantong, JS, China.
[Shi, Wei] Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, #20 Xisi Road, 226001 Nantong, JS, China.
[Wu, Xinhua] Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, #20 Xisi Road, 226001 Nantong, JS, China.
[Ni, Hongbing] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Ju, Shaoqing] Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, #20 Xisi Road, 226001 Nantong, JS, China.
RP Ju, Sh (reprint author), Affiliated Hospital of Nantong University, Surgical Comprehensive Laboratory, 226001 Nantong, China.
EM jsq814@hotmail.com;274391898@qq.com
CR Comert M, Gunes AE, Sahin F, Saydam G, 2013, Quality of Life and Supportive Care inMultipleMyeloma. Turk J Haematol 30(3): 234–246
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Fuchs O, 2013, Targeting of NF-kappaB signaling pathway, other signaling pathways and epigenetics in therapy of multiple myeloma. Cardiovasc Hematol Disord Drug Targets 13(1):16–34
Calin GA, Croce CM, 2006, MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866
Kong YW, Ferland-McCollough D, Jackson TJ, Jackson TJ, Bushell M, 2012, microRNAs in cancer management. Lancet Oncol 13(6):e249–e258
Corsini LR, Bronte G, Terrasi M, Amodeo V, Fanale D, Fiorentino E, Cicero G, Bazan V, Russo A, 2012, The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies. Expert Opin Ther Targets 16(Suppl 2):S103–S109
Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI, Croce CM, 2008, MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci U S A 105(35):12885– 12890
Corthals SL, Sun SM, Kuiper R, de Knegt Y, Broyl A, van der Holt B, Beverloo HB, Peeters JK, el Jarari L, Lokhorst HM, Zweegman S, Jongen-LavrencicM, Sonneveld P, 2011, MicroRNA signatures characterize multiple myeloma patients. Leukemia 25(11):1784– 1789
Gao SM, Xing CY, Chen CQ, Lin SS, Dong PH, Yu FJ, 2011, miR- 15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level. J Exp Clin Cancer Res 30:110
Hao M, Zhang L, An G, Meng H, Han Y, Xie Z, Xu Y, Li C, Yu Z, Chang H, Qiu L, 2011, Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression. Leuk Lymphoma 52(9):1787–1794
Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Stadtmauer EA, O’Connor OA, Shi H, Boral AL, Goy A, 2006, Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 24:4867–4874
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Yu J, Qiu X, Shen X, ShiW,Wu X, Gu G, Zhu B, Ju S, 2014)miR- 202 expression concentration and its clinical significance in the serum of multiple myelomapatients. Ann Clin Biochem 51:543– 549
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Coppo R, 2014, Proteasome inhibitors in progressive renal diseases. Nephrol Dial Transplant 29(Suppl 1):i25–i30
Wen J, Feng Y, Huang W, Chen H, Liao B, Rice L, Preti HA, Kamble RT, Zu Y, Ballon DJ, Chang CC, 2010, Enhanced antimyeloma cytotoxicity by the combination of arsenic trioxide and bortezomib is further potentiated by p38 MAPK inhibition. Leuk Res 34(1):85–92
Kobayashi T, Kuroda J, Ashihara E, Oomizu S, Terui Y, Taniyama A, Adachi S, Takagi T, Yamamoto M, Sasaki N, Horiike S, Hatake K, Yamauchi A, Hirashima M, Taniwaki M, 2010, Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways. Leukemia 4:843–850
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 531
EP 539
DI 10.1007/s12253-015-0035-4
PG 9
ER
PT J
AU Qiao, D
Li, M
Pu, J
Wang, W
Zhu, W
Liu, H
AF Qiao, Dongfeng
Li, Ming
Pu, Juan
Wang, Wanwei
Zhu, Weiguo
Liu, Haiyan
TI Loss of Protein Tyrosine Phosphatase Receptor J Expression Predicts an Aggressive Clinical Course in Patients with Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Protein tyrosine phosphatase receptor J; Esophageal squamous cell carcinoma; Progression; Migration; Invasion
ID Protein tyrosine phosphatase receptor J; Esophageal squamous cell carcinoma; Progression; Migration; Invasion
AB Protein Tyrosine Phosphatase Receptor J (PTPRJ) has been reported to be a tumor suppressor in various human cancers. The aim of this study was to investigate the clinical significance of PTPRJ in ESCC patients and its effects on biological behaviors of ESCC cells. PTPRJ expression, at mRNA and protein levels, were respectively detected by quantitative real-time PCR, western blot and immunohistochemistry, based on 106 newly diagnosed ESCC patients. The associations between PTPRJ expression and clinicopathological characteristics of ESCC patients were statistically analyzed. Then, the effects of PTPRJ in migration and invasion were determined by wound healing and transwell assays based on ESCC cell line transfected with siRNA or expression vector of PTPRJ. Expression of PTPRJ at mRNA and protein levels were both significantly lower in ESCC tissues than those in normal esophageal mucosa. Immunohistochemistry showed that PTPRJ protein was localized in the cytoplasm of cancer cells in ESCC tissues. In addition, PTPRJ downregulation was found to be closely correlated with advanced tumor stage (P = 0.01) and poor differentiation (P = 0.03).Moreover, knockdown of PTPRJ in KYSE510 cells could significantly promote cell migration and invasion (both P < 0.05), which were reversed by the restoration of PTPRJ expression in vitro (both P < 0.05). Our data offer the convincing evidence that loss of PTPRJ expression may predict an aggressive clinical course in ESCC patients. PTPRJ may function as a tumor suppressor and play an important role in the regulation of ESCC cell motility, suggesting its potentials as a therapeutic agent for human ESCC.
C1 [Qiao, Dongfeng] People’s Hospital of Lianshui County, Department of Radiotherapy Pathology, 223400 Lianshui, China.
[Li, Ming] People’s Hospital of Xuyi County, Department of Radiotherapy Pathology, 211700 Xuyi, China.
[Pu, Juan] People’s Hospital of Lianshui County, Department of Radiotherapy Pathology, 223400 Lianshui, China.
[Wang, Wanwei] People’s Hospital of Lianshui County, Department of Radiotherapy Pathology, 223400 Lianshui, China.
[Zhu, Weiguo] Nanjing Medical University, Huai’an First People’s Hospital, Department of Radiotherapy Oncology, 223300 Huainan, China.
[Liu, Haiyan] Nanjing Medical University, Huai’an First People’s Hospital, Department of Pathology, 223300 Huainan, China.
RP Zhu, W (reprint author), Nanjing Medical University, Huai’an First People’s Hospital, Department of Radiotherapy Oncology, 223300 Huainan, China.
EM jshazwg@126.com
CR Baba Y, Watanabe M, Yoshida N, Baba H, 2014, Neoadjuvant treatment for esophageal squamous cell carcinoma. World J Gastrointest Oncol 6:121–128
Shang L, Wang M, 2013, Molecular alterations and clinical relevance in esophageal squamous cell carcinoma. Front Med 7:401– 410
Li JS, Ying JM, Wang XW, Wang ZH, Tao Q, Li LL, 2013, Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma. Chin J Cancer 32:3–11
Kruger J, Brachs S, Trappiel M, Kintscher U, Meyborg H, Wellnhofer E, Thone-Reineke C, Stawowy P, Ostman A, Birkenfeld AL, Bohmer FD, Kappert K, 2015, Enhanced insulin signaling in density-enhanced phosphatase-1, DEP-1, knockout mice. Mol Metab 4:325–336
Petermann A, Stampnik Y, Cui Y, Morrison H, Pachow D, Kliese N, Mawrin C, Bohmer FD, 2015, Deficiency of the proteintyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells. J Neuro- Oncol 122:451–459
Spring K, Lapointe L, Caron C, Langlois S, Royal I, 2014, Phosphorylation of DEP-1/PTPRJ on threonine 1318 regulates Src activation and endothelial cell permeability induced by vascular endothelial growth factor. Cell Signal 26:1283– 1293
Ortuso F, Paduano F, Carotenuto A, Gomez-Monterrey I, Bilotta A, Gaudio E, Sala M, Artese A, Vernieri E, Dattilo V, Iuliano R, Brancaccio D, Bertamino A, Musella S, Alcaro S, Grieco P, Perrotti N, Croce CM, Novellino E, Fusco A, Campiglia P, Trapasso F, 2013, Discovery of PTPRJ agonist peptides that effectively inhibit in vitro cancer cell proliferation and tube formation. ACS Chem Biol 8:1497–1506
Smart CE, Askarian Amiri ME, Wronski A, Dinger ME, Crawford J, Ovchinnikov DA, Vargas AC, Reid L, Simpson PT, Song S, Wiesner C, French JD, Dave RK, da Silva L, Purdon A, Andrew M, Mattick JS, Lakhani SR, Brown MA, Kellie S, 2012, Expression and function of the protein tyrosine phosphatase receptor J, PTPRJ, in normal mammary epithelial cells and breast tumors. PLoS One 7:e40742
Spring K, Fournier P, Lapointe L, Chabot C, Roussy J, Pommey S, Stagg J, Royal I, 2015, The protein tyrosine phosphatase DEP-1/ PTPRJ promotes breast cancer cell invasion and metastasis. Oncogene In press
Yan CM, Zhao YL, Cai HY, Miao GY, Ma W, 2015, Blockage of PTPRJ promotes cell growth and resistance to 5-FU through activation of JAK1/STAT3 in the cervical carcinoma cell line C33A. Oncol Rep 33:1737–1744
Chen G, Peng J, Zhu W, Tao G, Song Y, Zhou X, Wang W, 2014, Combined downregulation of microRNA-133a and microRNA- 133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy. Med Oncol 31:263
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM, 2010, Estimates of worldwide burden of cancer in 2008. Int J Cancer 127:2893–2917
Xu X, Lan W, Jin X, Wang B, Yan H, Chen X, Lai X, Zhang L, Zhang X, Li Z, 2014, Regulated expression of PTPRJ by COX-2/ PGE2 axis in endothelial cells. PLoS One 9:e114996
Dave RK, Dinger ME, Andrew M, Askarian-Amiri M, Hume DA, Kellie S, 2013, Regulated expression of PTPRJ/CD148 and an antisense long noncoding RNA in macrophages by proinflammatory stimuli. PLoS One 8:e68306
Aya-Bonilla C, Green MR, Camilleri E, Benton M, Keane C, Marlton P, Lea R, Gandhi MK, Griffiths LR, 2013, High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to Non- Hodgkin’s lymphoma. Genes Chromosom Cancer 52:467–479
Liotta LA, Kohn EC, 2001, The microenvironment of the tumourhost interface. Nature 411:375–379
WangW, Goswami S, Sahai E, 2005, Tumor cells caught in the act of invading: their strategy for enhanced cell motility. Trends Cell Biol 15:138–145
Ridley AJ, Schwartz MA, Burridge K, 2003, Cell migration: integrating signals from front to back. Science 302:1704–1709
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 541
EP 547
DI 10.1007/s12253-015-0036-3
PG 7
ER
PT J
AU Guo, Yl
You, K
Geng, L
Qiao, J
AF Guo, Yan-li
You, Ke
Geng, Li
Qiao, Jie
TI Clinical Performance of APTIMA Human Papillomavirus (HPV) 16 18/45 mRNA Genotyping Testing for the Detection of Cervical Intraepithelial Neoplasia 3 (CIN3) or Cancer in a Select Group of Chinese Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; HPV mRNA genotyping; Cervical cancer; Screening
ID Human papillomavirus; HPV mRNA genotyping; Cervical cancer; Screening
AB HPV type was evaluated in a select group of Chinese women that were positive with hybrid capture, and correlations were performed between the pathology found, the type of virus and a semiquantitation from the hybrid capture results. Totally 394 referred high-risk-HPV-positive women evaluated by Hybrid Capture 2 (HC-2) assay were enrolled. Before colposcopy, cervical specimens were collected from all participants and suspended into PreservCytcollection medium (Hologic Inc., Marlborough, MA), and tested with the APTIMA HPV16 18/45 mRNA assay. Colposcopy and diagnostic biopsies were done on all participants. Viral load was assessed by HC2 assay. Totally 55 women were diagnosed as CIN 3 plus cancer (≥CIN3), and the prevalence of HPV16/18/ 45 was 65.5 % (95 % confidence interval [CI], 52.9–78.0 %) among these ≥CIN3 women. Compared with the group with positive HC2 but negative HPV16/18/45, the odds ratio (OR) to identify ≥CIN3 was 6.3 (95%CI, 3.2–12.3) for HPV16 and 3.2 (95 % CI, 1.4–7.2) for HPV18/45. When using ≥CIN3 as an endpoint, the sensitivity and specificity was 65.5 % (95 % CI, 52.9–78.0 %) and 72.0 % (95 % CI, 67.2–76.8 %). In the case of HPV16/18/45 negative, no high HPV load had a statistically significant increased risk for the prevalence of ≥CIN3. HPV16, 18 and 45 infection is a major cause for ≥CIN3 in Chinese women. Women with positive HPV16/18/ 45 should be referred to colposcopy immediately. HPV load was not suitable for the further triaged of the HPV16/18/45 negative cases.
C1 [Guo, Yan-li] Peking University Third Hospital, Department of Obstetrics and Gynecology, Number 49 Huayuanbei Road Haidian District, 100191 Beijing, China.
[You, Ke] Peking University Third Hospital, Department of Obstetrics and Gynecology, Number 49 Huayuanbei Road Haidian District, 100191 Beijing, China.
[Geng, Li] Peking University Third Hospital, Department of Obstetrics and Gynecology, Number 49 Huayuanbei Road Haidian District, 100191 Beijing, China.
[Qiao, Jie] Peking University Third Hospital, Department of Obstetrics and Gynecology, Number 49 Huayuanbei Road Haidian District, 100191 Beijing, China.
RP Geng, L (reprint author), Peking University Third Hospital, Department of Obstetrics and Gynecology, 100191 Beijing, China.
EM gengli57@163.com
CR Walboomers JM, JacobsMV,ManosMM, Bosch FX, Kummer JA, Shah KVet al, 1999, Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19
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Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M et al, 2014, Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 383:524–532
Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T et al, 2013, Five-year risk of CIN3+ and cervical cancer for women who test Pap-negative, but are HPV-positive. J Low Genit Tract Dis 17:S56–S63
Saslow D, Solomon D, Lawson HW, KillackeyM, Kulasingam SL, Cain J et al, 2012, American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer. Am J Clin Pathol 137:516–542
Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M et al, 2013, 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 121:829–846
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 549
EP 554
DI 10.1007/s12253-015-0029-2
PG 6
ER
PT J
AU Hu, B
Yan, X
Liu, F
Zhu, Ch
Zhou, H
Chen, Y
Liu, J
Gu, X
Ni, R
Zhang, T
AF Hu, Baoying
Yan, Xia
Liu, Fang
Zhu, Changlai
Zhou, Huiling
Chen, Yuyan
Liu, Jinxia
Gu, Xingxing
Ni, Runzhou
Zhang, Tianyi
TI Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human hepatocellular carcinoma (HCC); PTPN9; Cell proliferation; Prognosis
ID Human hepatocellular carcinoma (HCC); PTPN9; Cell proliferation; Prognosis
AB Human hepatocellular carcinoma (HCC) is one of the most common malignant cancers, whose molecular mechanisms is remains largely. PTPN9 has recently been reported to play a critical role in breast cancer development. However, the role of PTPN9 in human HCC remains elusive. The present study aimed at investigating the potential role of PTPN9 in HCC. Western blot and immunohistochemistry were used to examine the expression of PTPN9 protein in HCC and adjacent non-tumorous tissues in 45 patients. Furthermore, Cell Counting Kit-8, flow cytometry and RNA interference experiments were performed to analyze the role of PTPN9 in the regulation of HCC cell proliferation. We showed that the expression level of PTPN9 was significantly reduced in HCC, compared with adjacent non-tumorous tissues. PTPN9 expression was inversely associated with Tumor size (P= 0.014), serum AFP level (P=0.004) and Ki-67 expression. Low expression of PTPN9 predicted poor survival in HCC patients. Moreover, PTPN9 interference assay that PTPN9 inhibited cell proliferation in HepG2 cells. Cell apoptosis assay revealed that, silencing of PTPN9 expression significantly reduced cell apoptosis, compared with control ShRNA treatment group. Our results suggested that PTPN9 expression was down-regulated in HCC tumor tissues, and reduced PTPN9 expression was associated with worsened overall survival in HCC patients. Depletion of PTPN9 inhibits the apoptosis and promotes the proliferation of HCC cells.
C1 [Hu, Baoying] Nantong University, Medical College, Basic Medic Research Centre, 226001 Nantong, Jiangsu, China.
[Yan, Xia] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, Jiangsu, China.
[Liu, Fang] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, Jiangsu, China.
[Zhu, Changlai] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, Jiangsu, China.
[Zhou, Huiling] Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, 226019 Nantong, Jiangsu, China.
[Chen, Yuyan] Nantong University, Medical College, Class 5, Grade 13, Clinical Medicine, 226001 Nantong, Jiangsu, China.
[Liu, Jinxia] Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, 226019 Nantong, Jiangsu, China.
[Gu, Xingxing] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, Jiangsu, China.
[Ni, Runzhou] Affiliated Hospital of Nantong University, Department of Gastroenterology, 226001 Nantong, Jiangsu, China.
[Zhang, Tianyi] Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, Jiangsu, China.
RP Zhang, T (reprint author), Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, 226001 Nantong, China.
EM ntdxzty@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 555
EP 565
DI 10.1007/s12253-015-0038-1
PG 11
ER
PT J
AU Jelicic, J
Balint, TM
Jovanovic, PM
Boricic, N
Micev, M
Stojsic, J
Antic, D
Andjelic, B
Bila, J
Balint, B
Pavlovic, S
Mihaljevic, B
AF Jelicic, Jelena
Balint, Todorovic Milena
Jovanovic, Perunicic Maja
Boricic, Novica
Micev, Marjan
Stojsic, Jelena
Antic, Darko
Andjelic, Bosko
Bila, Jelena
Balint, Bela
Pavlovic, Sonja
Mihaljevic, Biljana
TI The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and High CD44 Tumor Cell Expression in Non Hodgkin Lymphomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lymphoma; Lymphocyte-to-monocyte count; Adhesion; Angiogenesis
ID Lymphoma; Lymphocyte-to-monocyte count; Adhesion; Angiogenesis
AB Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/ partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD> 42 blood vessels/0.36 mm2 correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p =0.014). High CD44s expression in FL correlated with inferior EFS and OS (p<0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51–7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08–1.79, p=0.01). Furthermore, in FL, ALC/ AMC mostly influenced OS (HR 5.21, 95 % CI 1.17–23.21, p =0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06– 14.95, p =0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).
C1 [Jelicic, Jelena] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
[Balint, Todorovic Milena] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
[Jovanovic, Perunicic Maja] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Boricic, Novica] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Micev, Marjan] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Stojsic, Jelena] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Antic, Darko] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
[Andjelic, Bosko] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
[Bila, Jelena] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
[Balint, Bela] MMA, Institute for Transfusiology and HemobiologyBelgrade, Serbia.
[Pavlovic, Sonja] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Mihaljevic, Biljana] Clinical Center of Serbia, Clinic for Hematology, Koste Todorovica 2 str, 11000 Belgrade, Serbia.
RP Balint, TM (reprint author), Clinical Center of Serbia, Clinic for Hematology, 11000 Belgrade, Serbia.
EM bb.lena@gmail.com
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Ribatti D,Nico B, Ranieri G et al, 2013, The role of angiogenesis in human non-Hodgkin lymphomas. Neoplasia 15:231–238
Nagel S, Hirschmann P, Dirnhofer S et al, 2010, Coexpression of CD44 variant isoforms and receptor for hyaluronic acid-mediated motility, RHAMM, CD168, is an International Prognostic Index and C-MYC gene status-independent predictor of poor outcome in diffuse large B-cell lymphomas. Exp Hematol 38:38–45
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 567
EP 577
DI 10.1007/s12253-015-0032-7
PG 11
ER
PT J
AU Szanto, A
Szabo, K
Nagy, G
Molnar, Cs
Zeher, M
AF Szanto, Antonia
Szabo, Katalin
Nagy, Gabor
Molnar, Csaba
Zeher, Margit
TI Characterization and Comparison of Patient Subgroups Suspicious for IgG4-Related Disease and Malignant Lymphoma in Patients Followed-up for Sjogren’s Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IgG4-related disease; Malignant lymphoma; Sjogren’s syndrome
ID IgG4-related disease; Malignant lymphoma; Sjogren’s syndrome
AB Differential diagnosis of patients with Sjogren’s syndrome (SS), IgG4-related disease (IgG4-RD) and SS patients having high risk for lymphoma (LHR) can be challenging. Some patients with IgG4-RD might be misdiagnosed as having SS. There are special symptoms of SS that raise the possibility of IgG4-RD whereas other symptoms identify patients as having LHR. The purpose of this study was to characterize and compare patients with SS, possible IgG4-RD and SS patients with LHR. Sixty-five SS patients were divided into 4 subgroups according to having possible IgG4-RD (n = 15), LHR (n = 16), eligible for both aforementioned groups (n = 20) and not eligible for either group (n = 14), respectively. Four patients fulfilled the diagnostic criteria for IgG4-RD. The serum levels of IgG4 were significantly higher in patients suspicious for IgG4-RD compared to that of LHR patients (0.46 g/l vs. 0.12 g/l, p = 0.032). Shared features of the patient groups (salivary gland swelling (SGS) and lymphadenopathy), were separately analysed: SGS patients had higher IgG4/IgG ratio (p = 0.036), lymphadenopathic patients had higher IgG4 levels (p = 0.042). Some patients may be "hidden" under the diagnosis of SS. Although patients with LHR and patients with possible IgG4-RD share some symptoms, they differ significantly regarding IgG4 levels and IgG4/IgG ratio.
C1 [Szanto, Antonia] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, 22 Moricz Zs. Krt, H-4032 Debrecen, Hungary.
[Szabo, Katalin] Josa Andras County Hospital, Department of Pediatrics, 68 Szent Istvan Street, H-4400 Nyiregyhaza, Hungary.
[Nagy, Gabor] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, 22 Moricz Zs. Krt, H-4032 Debrecen, Hungary.
[Molnar, Csaba] University of Debrecen, Faculty of Medicine, Department of Pathology, 98 Nagyerdei Krt, H-4032 Debrecen, Hungary.
[Zeher, Margit] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, 22 Moricz Zs. Krt, H-4032 Debrecen, Hungary.
RP Zeher, M (reprint author), University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, H-4032 Debrecen, Hungary.
EM zeher@iiibel.dote.hu
CR Masaki Y, Kurose N, Umehara H, 2011, IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. J Clin Exp Hematopathol 1:13–20
Okazaki K, Uchida K, Research Committee Members, 2009, Proposal of the Concept and diagnostic criteria of IgG4-related disease, in Japanese). Annual reports of research committee of intractable diseases supported by Ministry of Health, Labour and Welfare of Japan 25–30
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H, Kamisawa T, Shimosegawa T, Shimatsu A, Nakamura S, Ito T, Notohara K, Sumida T, Tanaka Y, Mimori T, Chiba T, Mishima M, Hibi T, Tsubouchi H, Inui K, Ohara H, 2012, Comprehensive diagnostic criteria for IgG4-related disease, IgG4-RD). Mod Rheumatol 22:21–30
Vitali C, Bombardieri S, Jonsson R, HMM, EL A, SE C, TE D, PC F, RI F, SS K, SR P, Talal N, MH W, European Study Group on Classification Criteria for Sjogren's Syndrome, 2002, Classification criteria for sjogren’s syndrome: a revised version of the European criteria proposed by the American-European consensus group. Ann Rheum Dis 61:554–558
Geyer JT, Desphande V, 2011, IgG4-associated sialadenitis. Curr Opin Rheumatol 23:95–101
Ioannidis JP, Vassioliou VA, Moutsopoulos HM, 2002, Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary sjogren’s syndrome. Arthritis Rheum 46:741–747
Seror R, Ravaud P, Bowman S, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C, Sjogren's Task Force EULAR, 2010, EULAR sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary sjogren’s syndrome. Ann Rheum Dis 69:1103–1109
Szanto A, Nagy G, Cs M, Griger Z, Tarr T, Zeher M, 2014, Description of patients with IgG4-related disease from a Hungarian center. Scand J Rheumatol 43:334–337
Ryu JH, Horie R, Sekiguchi H, Peikert T, Yi ES, 2012, Spectrum of disorders associated with elevated serum IgG4 levels encountered in clinical practice. Int J Rheumatol 232960., DOI 10.1155/2012/ 232960
Moriyama M, Tanaka A, Maehara T, Ohyama Y, Shimizu M, Nakashima H, Hayashida JN, Shinozaki S, Kubo Y, Furukawa S, Kikuta T, Nakamura S, 2013, Clinical characteristics of mikulicz’s disease as an IgG4-related disease. Clin Oral Investig 17:1995–2002
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Quartuccio L, Isola M, Baldini C, Priori R, Bocci EB, Carubbi F, Maset M, Gregoraci G, Della Mea V, Salvin S, De Marchi G, Luciano N, Colafrancesco S, Alunno A, Giacomelli R, Gerli R, Valesini G, Bombardieri S, De Vita S, 2014, Biomarkers of lymphoma in sjogren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. J Autoimmun 51:75–80
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Laco J, Ryska A, Celakovsky P, Dolezalova H, Mottl R, Tucek L, 2011, Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe. Histopathology 58:1157–1163
Stone JH, Khosroshahi A, Desphande V, Chan JKC, Heathcote JG, Aalberse R, Azumi A, Bloch DB, Brugge WR, Carruthers MN, Cheuk W, Cornell L, Castillo CF, Ferry JA, Forcione D, Kloppel G, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, MasakiY, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani D, Sato Y, Smyrk T, Stone JR, Takahira M, Umehara H, Webster G, Yamamoto M, Yi E, Yoshino T, Zamboni G, Zen Y, Chari S, 2012, Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 64:3061–3067
Moriyama M, Furukawa S, Kawano S, Goto Y, Kiyoshima T, Tanaka A, Maehara T, Hayashida J-N, Ohta M, Nakamura S, 2014, The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called mikulicz’s disease. Int J Oral Maxillofac Surg 43:1276–1281
Shimizu Y, Yamamoto M, Naishiro Y, Sudoh G, Ishigami K, Yajima H, Tabeya T, Matsui M, Suzuki C, Takahashi H, Seki N, Himi T, YamashitaK, Noguchi H,Hasegawa T, Suzuki Y, Honda S, Abe T, Imai K, Shinomura Y, 2013, Necessity of early intervention for IgG4-related disease - delayed treatment induces fibrosis progression. Rheumatology, Oxford, 52:679–683
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 579
EP 585
DI 10.1007/s12253-016-0041-1
PG 7
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of AKAP9 Gene in Gastric and Colorectal Cancers with High Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AKAP9; Fameshift mutation; Cancer; Microsatellite instability
ID AKAP9; Fameshift mutation; Cancer; Microsatellite instability
AB A-kinase-anchoring protein 9 (AKAP9) coordinates the cellular location and function of protein kinase A. AKAP9 plays an important role in centrosome duplication, cell cycle progression and maintenance of cell membrane integrity, alterations of which contribute to tumorigenesis. Somatic mutations of AKAP9 gene have been detected in many cancers including gastric (GC) and colorectal cancers (CRC), but the mutation status with respect to microsatellite instability (MSI) has not been reported. In a public database, we found that AKAP9 gene had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with MSI. We analyzed the mutations in 79 GCs and 124 CRCs including high MSI (MSI-H) and microsatellite stable/low MSI (MSS/MSI-L) cases by single-strand conformation polymorphism analysis and DNA sequencing. Overall, we found AKAP9 frameshift mutations in 4 (11.7 %) GCs and 20 (17.7 %) CRCs with MSI-H (24/113), but not in MSS/MSI-L cancers (0/90) (p < 0.001). In addition, we analyzed intratumoral heterogeneity (ITH) of AKAP9 frameshift mutations in 16 CRCs and found that five CRCs (31.3 %) harbored regional ITH of the AKAP9 frameshift mutations. Our data indicate that AKAP9 gene harbors not only somatic frameshift mutations but also mutational ITH, which together may be features of GC and CRC with MSI-H. Our results also suggest that regional mutation analysis is needed for a better evaluation of mutation status in these tumors to overcome ITH.
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Colledge M, Scotte JD, 1999, AKAPs: from structure to function. Trends Cell Biol 9:216–221
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 587
EP 592
DI 10.1007/s12253-016-0042-0
PG 6
ER
PT J
AU Ozdemir, AD
Usubutun, A
AF Ozdemir, Ates Deniz
Usubutun, Alp
TI PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PAX2; PAX8; Mucinous ovarian tumor; Mucinous ovarian carcinoma; Borderline seromucinous tumor
ID PAX2; PAX8; Mucinous ovarian tumor; Mucinous ovarian carcinoma; Borderline seromucinous tumor
AB Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis s t i l l r e m a i n s a m y s t e r y. PAX2 a n d PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were reevaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity–similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.
C1 [Ozdemir, Ates Deniz] Hacettepe University, Faculty of Medicine, Department of PathologyAnkara, Turkey.
[Usubutun, Alp] Hacettepe University, Faculty of Medicine, Department of PathologyAnkara, Turkey.
RP Ozdemir, AD (reprint author), Hacettepe University, Faculty of Medicine, Department of Pathology, Ankara, Turkey.
EM denizates010@gmail.com
CR Seidman JD, Kurman RJ, Ronnett BM, 2003, Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 27(7):985–993
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 593
EP 599
DI 10.1007/s12253-016-0040-2
PG 7
ER
PT J
AU Sulzyc-Bielicka, V
Domagala, P
Bielicki, D
Safranow, K
Rogowski, W
Domagala, W
AF Sulzyc-Bielicka, Violetta
Domagala, Pawel
Bielicki, Dariusz
Safranow, Krzysztof
Rogowski, Wojciech
Domagala, Wenancjusz
TI E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; E2F1; Thymidylate synthase; 5FU-based therapy
ID Colorectal cancer; E2F1; Thymidylate synthase; 5FU-based therapy
AB The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR= 3,78, P=0,009) and DFS (HR= 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P=0.008) and OS (P=0.01). About 37 and 31 % difference in 3-year DFS and OS respectivelywere seen between patients w i t h E2F1+TS+ v s . E2F1-TS- c o l o n c a n c e r immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.
C1 [Sulzyc-Bielicka, Violetta] Pomeranian Medical University, Department of Clinical OncologySzczecin, Poland.
[Domagala, Pawel] Pomeranian Medical University, Department of Pathology, Unii Lubelskiej 1, 71-252 Szczecin, Poland.
[Bielicki, Dariusz] Pomeranian Medical University, Department of GastroenterologySzczecin, Poland.
[Safranow, Krzysztof] Pomeranian Medical University, Department of Biochemistry and Medical ChemistrySzczecin, Poland.
[Rogowski, Wojciech] University of Warmia and Mazury, Department of OncologyOlsztyn, Poland.
[Domagala, Wenancjusz] Pomeranian Medical University, Department of Pathology, Unii Lubelskiej 1, 71-252 Szczecin, Poland.
RP Domagala, W (reprint author), Pomeranian Medical University, Department of Pathology, 71-252 Szczecin, Poland.
EM wenek@pum.edu.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 601
EP 608
DI 10.1007/s12253-016-0043-z
PG 8
ER
PT J
AU Chen, J
Hu, L
Chen, J
Pan, Q
Ding, H
Xu, G
Zhu, P
Wen, X
Huang, K
Wang, Y
AF Chen, Jie
Hu, Lijuan
Chen, Jian
Pan, Qinshi
Ding, Hongyan
Xu, Gang
Zhu, Peiwu
Wen, Xiusu
Huang, Keta
Wang, Yumin
TI Detection and Analysis of Wnt Pathway Related lncRNAs Expression Profile in Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; LncRNAs; Wnt pathway; Expression profile
ID Lung adenocarcinoma; LncRNAs; Wnt pathway; Expression profile
AB Studies have shown that the expression profile of Wnt signaling pathway is very important in lung adenocarcinoma (LAD) and some lncRNAs can regulate the expression of key molecules of Wnt pathway. However, Wnt pathway related lncRNAs are not systematically analyzed and detected in lung adenocarcinoma. We used a high-throughput microarray to compare the lncRNA expression profiles in LAD and corresponding normal tissue (NT) samples. Several candidate Wnt pathway related lncRNAs were verified by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis. We found that 232 Wnt pathway related lncRNAs were obviously expressed (≥2-fold change) in lung adenocarcinoma samples and 13 Wnt pathway related lncRNAs were aberrantly expressed in lung adenocarcinoma compared with matched histologically normal lung tissues by qPCR. Among these, RP11-181G12.2 and RP11-89 K21.1 were the most aberrantly expressed lncRNAs. Our study ascertained the expression of Wnt pathway related lncRNAs in lung adenocarcinoma. The results revealed that many Wnt pathway related lncRNAs were differentially expressed in lung adenocarcinoma tissues, suggesting that they may play a key role in tumor development.
C1 [Chen, Jie] The First Affiliated Hospital of Wenzhou Medical University, Department of Intensive Care UnitWenzhou, Zhejiang Province, China.
[Hu, Lijuan] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Chen, Jian] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Pan, Qinshi] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Ding, Hongyan] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Xu, Gang] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Zhu, Peiwu] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Wen, Xiusu] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
[Huang, Keta] The First Affiliated Hospital of Wenzhou Medical University, Department of PathologyWenzhou, Zhejiang Province, China.
[Wang, Yumin] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang Province, China.
RP Wang, Y (reprint author), The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, China.
EM wym0577@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 609
EP 615
DI 10.1007/s12253-016-0046-9
PG 7
ER
PT J
AU Kanizsai, Sz
Ongradi, J
Aradi, J
Nagy, K
AF Kanizsai, Szilvia
Ongradi, Jozsef
Aradi, Janos
Nagy, Karoly
TI New Approach for Inhibition of HIV Entry: Modifying CD4 Binding Sites by Thiolated Pyrimidine Derivatives
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIV entry; Thiolated pyrimidine derivatives; HIV-1 pseudotypes; Redox processes; CD4
ID HIV entry; Thiolated pyrimidine derivatives; HIV-1 pseudotypes; Redox processes; CD4
AB Thiolated pyrimidine derivatives have been synthetized and their antiretroviral effect against human immunodeficiency virus type 1 (HIV-1IIIB) and HIV-1 chimeric pseudovirions have been quantitatively determined in cellbased viral infectivity assays including syncytium inhibition assay as well as a single-cycle viral infection assay on HeLaCD4- LTR/ß-gal cells. Pseudotype virions prepared bearing HIV-1 envelope preference for CCR5 coreceptor, CXCR4 coreceptor or for both, respectively, with a HIV-1 core containing luciferase reporter gene were able to infect susceptible cells but are replication defective so unable to replicate in the cells . Data indicate that thiolated pyrimidine derivatives inhibited effectively virally induced cell fusion in vitro aswell as infectivity of primary HIV- 1IIIB strain and HIV-1 pseudovirions using chemokine receptors CCR5 or CXCR4 or both for virus entry a dose dependent manner. Inhibition was selective, depended on the pseudovirus coreceptor preference. Our results suggest that some of these sulfur containing pyrimidines interact with redoxactive -SH groups required for successful HIV entry, including a redox active disulfide in the CD4 molecule as well as -SH groups in HIV viral envelope gp120. This mode of action is unique representing a new class of potential HIV entry inhibitors.
C1 [Kanizsai, Szilvia] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
[Ongradi, Jozsef] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
[Aradi, Janos] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Nagy, Karoly] Semmelweis University, Department of Medical MicrobiologyBudapest, Hungary.
RP Nagy, K (reprint author), Semmelweis University, Department of Medical Microbiology, Budapest, Hungary.
EM nagy.karoly@med.semmelweis-univ.hu
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Zarr M, Siliciano R, 2015, Stoichiometric parameters of HIV-1 entry. Virology 474:1–9
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 617
EP 623
DI 10.1007/s12253-016-0044-y
PG 7
ER
PT J
AU Yamada, Shi
Yanamoto, S
Naruse, T
Matsushita, Y
Takahashi, H
Umeda, M
Nemoto, KT
Kurita, H
AF Yamada, Shin-ichi
Yanamoto, Souichi
Naruse, Tomofumi
Matsushita, Yuki
Takahashi, Hidenori
Umeda, Masahiro
Nemoto, K Takayuki
Kurita, Hiroshi
TI Skp2 Regulates the Expression of MMP-2 and MMP-9, and Enhances the Invasion Potential of Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Skp2; invasion; metastasis; migration; oral squamous cell carcinoma
ID Skp2; invasion; metastasis; migration; oral squamous cell carcinoma
AB Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck regions and accounts for more than 90 % of cancers in the oral cavity. Sphase kinase-associated protein-2 (Skp2) is a member of the F-box protein family and the substrate recognition subunit of the Skp1-Cullin-F box protein E3 ubiquitin ligase complex. Skp2 is oncogenic and overexpressed in human cancers. The aims of the present study were to determine the clinicopathological significance of Skp2 in OSCC and clarify its function in OSCC cell lines in vitro. Multiple methods including immunohistochemical staining, RT-PCR, western blotting, migration and invasion assays, and siRNA transfection were employed in order to investigate the clinicopathological significance and molecular function of Skp2 in OSCC. The overexpression of Skp2 was more frequent in OSCC than in the normal oral epithelium. It was also more frequently detected in cancers with higher grades according to the Tclassification, N classification, and pattern of invasion. The high-Skp2 expression group had a significantly poorer prognosis, at 30.1 %, than that of the low-expression group, at 63.0 %. The downregulation of Skp2 decreased migration and invasion potentials in HSC3 cells. Moreover, the suppression of Skp2 reduced the enzyme activities of MMP-2 and MMP-9 via Sp1. Skp2 may be a prognostic factor in OSCC patients, and may also play crucial roles in the migration and invasion potentials of OSCC cells.
C1 [Yamada, Shin-ichi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Matsushita, Yuki] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Takahashi, Hidenori] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral OncologyNagasaki, Japan.
[Nemoto, K Takayuki] Nagasaki University Graduate School of Biomedical Sciences, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Department of Oral Molecular BiologyNagasaki, Japan.
[Kurita, Hiroshi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
RP Yamada, Shi (reprint author), Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 390-8621 Matsumoto, Japan.
EM yshinshin@shinshu-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 625
EP 632
DI 10.1007/s12253-016-0049-6
PG 8
ER
PT J
AU Ferrer-Font, L
Alcaraz, E
Plana, M
Candiota, PA
Itarte, E
Arus, C
AF Ferrer-Font, Laura
Alcaraz, Estefania
Plana, Maria
Candiota, Paula Ana
Itarte, Emilio
Arus, Carles
TI Protein Kinase CK2 Content in GL261 Mouse Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; CK2 content; Preclinical brain tumor; GBM therapeutic targets
ID Glioma; CK2 content; Preclinical brain tumor; GBM therapeutic targets
AB Glioblastoma (GBM) is the most prevalent and aggressive human glial tumour with a median survival of 14– 15 months. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment. Unfortunately, chemoresistence always ensues with concomitant tumour regrowth. Protein kinase CK2 (CK2) contributes to tumour development, proliferation, and suppression of apoptosis in cancer and it is overexpressed in human GBM. Targeting CK2 in GBM treatment may benefit patients. With this translational perspective in mind, we have studied the CK2 expression level by Western blot analysis in a preclinical model of GBM: GL261 cells growing orthotopically in C57BL/6 mice. The expression level of the CK2 catalytic subunit (CK2α) was higher in tumour (about 4-fold) and in contralateral brain parenchyma (more than 2-fold) than in normal brain parenchyma (p < 0.05). In contrast, no significant changes were found in CK2 regulatory subunit (CK2β) expression, suggesting an increased unbalance of CK2α/CK2β in GL261 tumours with respect to normal brain parenchyma, in agreement with a differential role of these two subunits in tumours.
C1 [Ferrer-Font, Laura] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
[Alcaraz, Estefania] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
[Plana, Maria] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
[Candiota, Paula Ana] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
[Itarte, Emilio] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
[Arus, Carles] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
RP Candiota, PA (reprint author), Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, 08193 Cerdanyola del Valles, Spain.
EM AnaPaula.Candiota@uab.cat
CR Buckner JC, 2003, Factors influencing survival in high-grade gliomas. Semin Oncol 30(6 Suppl 19):10–14
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 633
EP 637
DI 10.1007/s12253-015-9987-7
PG 5
ER
PT J
AU Sand, M
Bechara, GF
Skrygan, M
Sand, D
Gambichler, Th
Bromba, M
Stockfleth, E
Hessam, Sch
AF Sand, Michael
Bechara, G Falk
Skrygan, Marina
Sand, Daniel
Gambichler, Thilo
Bromba, Michael
Stockfleth, Eggert
Hessam, Schapoor
TI Mutation Scanning of D1705 and D1709 in the RNAse IIIb Domain of MicroRNA Processing Enzyme Dicer in Cutaneous Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Dicer; Mutation; MicroRNA
ID Melanoma; Dicer; Mutation; MicroRNA
AB Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metalion- binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain.
C1 [Sand, Michael] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
[Bechara, G Falk] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
[Skrygan, Marina] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
[Sand, Daniel] University of Michigan, Kellogg Eye Center, 1000 Wall Street, 48105 Ann Arbor, MI, USA.
[Gambichler, Thilo] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
[Bromba, Michael] Catholic Clinics of the Ruhr Peninsula, St. Josef Hospital, Department of Plastic Surgery, Heidbergweg 22-24, 45257 Essen, Germany.
[Stockfleth, Eggert] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
[Hessam, Schapoor] Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, Gudrunstr. 56, 44791 Bochum, Germany.
RP Sand, M (reprint author), Ruhr-University Bochum, St. Josef Hospital, Department of Dermatology, Venereology and Allergology, Dermatologic Surgery Unit, 44791 Bochum, Germany.
EM michael.sand@ruhr-uni-bochum.de
CR Sand M, 2014, The pathway of miRNA maturation. Methods Mol Biol 1095:3–10., DOI 10.1007/978-1-62703-703-7_1
Foulkes WD, Priest JR, Duchaine TF, 2014, DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 14(10):662–672., DOI 10.1038/nrc3802
Aksoy BA, Jacobsen A, Fieldhouse RJ, Lee W, Demir E, Ciriello G, Schultz N, Marks DS, Sander C, 2014, Cancer-associated recurrent mutations in RNase III domains of DICER1., DOI 10.1101/ 005686
Harbst K, Lauss M, Cirenajwis H,Winter C, Howlin J, Torngren T, Kvist A, Nodin B, Olsson E, Hakkinen J, Jirstrom K, Staaf J, Lundgren L, Olsson H, Ingvar C, Gruvberger-Saal SK, Saal LH, Jonsson G, 2014, Molecular and genetic diversity in the metastatic process of melanoma. J Pathol 233(1):39–50., DOI 10.1002/path. 4318
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Pellegrino L, Jacob J, Roca-Alonso L, Krell J, Castellano L, Frampton AE, 2013, Altered expression of the miRNA processing endoribonuclease dicer has prognostic significance in human cancers. Expert Rev Anticancer Ther 13(1):21–27., DOI 10.1586/era.12. 150
Sand M, Gambichler T, Sand D, Altmeyer P, Stuecker M, Bechara FG, 2011, Immunohistochemical expression patterns of the microRNA-processing enzyme dicer in cutaneous malignant melanomas, benign melanocytic nevi and dysplastic melanocytic nevi. Eur J Dermatol EJD 21(1):18–21., DOI 10. 1684/ejd.2011.1210
Nemlich Y, Greenberg E, Ortenberg R, Besser MJ, Barshack I, Jacob-Hirsch J, Jacoby E, Eyal E, Rivkin L, Prieto VG, Chakravarti N, Duncan LM, Kallenberg DM, Galun E, Bennett DC, Amariglio N, Bar-Eli M, Schachter J, Rechavi G, Markel G, 2013)MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor growth. J Clin Invest 123(6):2703–2718., DOI 10.1172/JCI62980
Mione M, Bosserhoff A, 2014, MicroRNAs in melanocyte and melanoma biology. Pigment Cell Melanoma Res., DOI 10.1111/ pcmr.12346
Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, Liang S, Naylor TL, Barchetti A, Ward MR, Yao G, Medina A, O’Brien-Jenkins A, Katsaros D, Hatzigeorgiou A, Gimotty PA, Weber BL, Coukos G, 2006, microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A 103(24):9136–9141., DOI 10.1073/pnas.0508889103
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 639
EP 641
DI 10.1007/s12253-015-0034-5
PG 3
ER
PT J
AU Damasdi, M
Jakab, F
Kovacs, K
Oldal, M
Kemenesi, G
Szabo, E
Valyi-Nagy, I
Pytel,
Farkas, L
Szanto,
AF Damasdi, Miklos
Jakab, Ferenc
Kovacs, Krisztina
Oldal, Miklos
Kemenesi, Gabor
Szabo, Eszter
Valyi-Nagy, Istvan
Pytel, Akos
Farkas, Laszlo
Szanto, Arpad
TI Prevalence and Type Diversity of Human Papillomaviruses in Penile Cancers in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Damasdi, Miklos] University of Pecs, Department of UrologyPecs, Hungary.
[Jakab, Ferenc] University of Pecs, Szentagothai Research Center, Ifjusag ut 20, H-7624 Pecs, Hungary.
[Kovacs, Krisztina] University of Pecs, Department of PathologyPecs, Hungary.
[Oldal, Miklos] University of Pecs, Szentagothai Research Center, Ifjusag ut 20, H-7624 Pecs, Hungary.
[Kemenesi, Gabor] University of Pecs, Szentagothai Research Center, Ifjusag ut 20, H-7624 Pecs, Hungary.
[Szabo, Eszter] Del-Pesti CentrumkorhazBudapest, Hungary.
[Valyi-Nagy, Istvan] Del-Pesti CentrumkorhazBudapest, Hungary.
[Pytel, Akos] University of Pecs, Department of UrologyPecs, Hungary.
[Farkas, Laszlo] University of Pecs, Department of UrologyPecs, Hungary.
[Szanto, Arpad] University of Pecs, Department of UrologyPecs, Hungary.
RP Jakab, F (reprint author), University of Pecs, Szentagothai Research Center, H-7624 Pecs, Hungary.
EM jakabf@gamma.ttk.pte.hu
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Bezerra AL, Lopes A, Santiago GH, Ribeiro KC, LatorreMR, Villa LL, 2001, Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer 91:2315–2321
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Guerrero D, Guarch R, Ojer A, Casas JM, Ropero S, Mancha A, et al., 2008, Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma. BJU Int 102:747–755
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 643
EP 646
DI 10.1007/s12253-015-0026-5
PG 4
ER
PT J
AU Girdhar, Y
Singh, N
Behera, D
Sharma, S
AF Girdhar, Yashila
Singh, Navneet
Behera, Digambar
Sharma, Siddharth
TI Combinations of the Variant Genotypes of CYP1A1, GSTM1 and GSTT1 are Associated with an Increased Lung Cancer Risk in North Indian Population: a Case-Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Girdhar, Yashila] Thapar University, Department of Biotechnology, 147004 Patiala, Punjab, India.
[Singh, Navneet] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary Medicine, Sector-12, 160012 Chandigarh, India.
[Behera, Digambar] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary Medicine, Sector-12, 160012 Chandigarh, India.
[Sharma, Siddharth] Thapar University, Department of Biotechnology, 147004 Patiala, Punjab, India.
RP Sharma, S (reprint author), Thapar University, Department of Biotechnology, 147004 Patiala, India.
EM siddharthsharma.phd@thapar.edu
CR Shah PP, Singh AP, Singh M, Mathur N, Pant MC, Mishra BN, Parmar D, 2008, Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer. Mutat Res 639:1–10
Jancova P, Anzenbacherb P, 2010, Anzenbacherova E, 2010, phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 154:103–116
Tefre T, Ryberg D, Haugen A, Nebert DW, Skaug V, Brogger A, Borresen AL, 1991, Human CYP1A1, cytochrome P 1450, gene: lack of association between the Msp I restriction fragment length polymorphism and incidence of lung cancer in a Norwegian population. Pharmacogenet Genomics 1:1
Altinisik J, Balta ZB, Aydin G, Ulutin T, Buyru N, 2010, Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer. Mol Biol Rep 37:263–267
Lee KM, Kang D, Clapper ML, Sundberg MI, Kihara MO, Kiyohara C, Min S, Lan Q, Le Marchand L, Lin P, Lung ML, Pinarbasi H, Pisani P, Srivatanakul P, Seow A, Sugimura H, Tokudome S, Yokota J, Taioli E, 2008, CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations. Cancer Epidemiol Biomark Prev 17:5
Cascorbi I, Brockmoller J, Roots I, 1996, A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages and impact on lung cancer susceptibility. Cancer Res 56:4965–4969
Shaffi SM, Shah AM, Bhat IA, Koul P, Ahmad SN, Siddiqi MA, 2009, CYP1A1 polymorphismand risk of lung cancer in the ethnic Kashmiri population. Asian Pacific J Cancer Prev 10:651–656
Kumar V, Singh S, Yadav CS, Ahmed RS, Gupta S, Pasha ST, Tripathi AK, Banerjee BD, 2009, CYP1A1 and CYP3A4 polymorphic variations in Delhi population of North India. Environ Toxicol Pharmacol 29:126–130
Shia X, Zhoua S,Wangb Z, Zhouc Z,Wanga Z, 2007, CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59, 155—163.
Zhan P,Wang Q, Qian Q,Wei SZ,Yu LK, 2011, CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: an updated metaanalysis and review. J Exp Clin Cancer Res 30:99
Sobti RC, Sharma S, Joshi A, Jindal SK, Janmeja A, 2004, Genetic polymorphism of the CYP1A1, CYP 2E1, GSTM1 & GSTT1 genes and lung cancer susceptibility in a north Indian population. Mol Cell Biochem 266:1–9
Liu X, Li Z, Zhang Z, ZhangW, LiW, Xiao Z, Liu H, Jiao H,Wang Y, Li G, 2014, Meta-analysis of GSTM1 null genotype and lung cancer risk in Asians.Med Sci Monit 20:1239–1245., DOI 10.12659/ MSM.890490
B’chir F, Aida T, Maurice JA, Saguem S, 2012, Glutathione Stransferase M1 and T1, CYP1A2-2467 T/delT polymorphisms and non-small cell lung cancer risk in Tunisian sample. Egypt J Med Hum Genet 13:307–312
Saarikoski ST, Voho A, Reinikainen M, Anttila S, Karjalainen A, Malaveille C, et al., 1998, Combined effect of polymorphic GST genes on individual susceptibility to lung cancer. Int J Cancer 77:516–521
Quinones L, Lucas D, Godoy J, Ca′ceres D, Berthou F, Varela N, Lee K, Acevedo C, Marti’nez L, Aguilera AM, Gil L, 2001, CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people. Cancer Lett 174:35–44
Sreeja LK, Syamala V, Hariharan S, Madhavan J, Devan SC, Ankathil R, 2005, Possible risk modification by CYO1A1, GSTM1 and GSTT1 gene polymorphism in lung cancer susceptibility in a south Indian population. J Hum Genet 50:618–662
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 647
EP 652
DI 10.1007/s12253-016-0058-5
PG 6
ER
PT J
AU Choi, JE
Kim, SM
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Inactivating Frameshift Mutation of INPP4B Encoding a PI3K Pathway Phosphatase in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Vanhaesebroeck B, Stephens L, Hawkins P, 2012, PIK3K signaling: the path to discovery and understanding. Nat Rev Mol Cell Biol 13: 195–203
Chen M, Nowak DG, Trotman LC, 2014, Molecular pathways: PI3K pathway phosphatases as biomarkers for cancer prognosis and therapy. Clin Cancer Res 20:3057–3063
Li Chew C, Lunardi A, Gulluni F, Ruan DT, Chen M, Salmena L, Nishino M, Papa A, Ng C, Fung J, Clohessy JG, Sasaki J, Sasaki T, Bronson RT, Hirsch E, Pandolfi PP, 2015, In vivo role of INPP4B in tumor and metastasis suppression through regulation of PI3K–AKT signaling at endosomes. Cancer Discov 5:740–751
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2016
VL 22
IS 3
BP 653
EP 654
DI 10.1007/s12253-016-0062-9
PG 2
ER
PT J
AU Davidson, TK
Zhu, Z
Fang, Y
AF Davidson, T Kristoffer
Zhu, Ziwen
Fang, Yujiang
TI Phytochemicals in the Fight Against Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Phytochemicals; Apple extract; Cancer
ID Phytochemicals; Apple extract; Cancer
AB Phytochemicals are chemical compounds from fruits, vegetables, or grains and they have been used to treat various diseases for thousands of years. More than one million people in the United States get cancer each year. Although recent advances in medicine have improved the outcomes for cancer patients, there is still a need for novel approaches in the fight against cancer. One such approach that has shown promise in recent years is the use of phytochemicals alone or as synergistic agents. In this review, we will discuss the use of phytochemicals as therapeutic agents against cancer with an emphasis on apple extract.
C1 [Davidson, T Kristoffer] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
EM yujiang.fang@dmu.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 655
EP 660
DI 10.1007/s12253-016-0045-x
PG 6
ER
PT J
AU Benharroch, D
Ariad, S
Tadmor, N
Nalbandyan, K
Lazarev, I
AF Benharroch, Daniel
Ariad, Samuel
Tadmor, Noa
Nalbandyan, Karen
Lazarev, Irena
TI Relevance of the Measles Virus Expression in Cancer - an Update
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Measles virus; Hodgkin lymphoma; Lung cancer; Breast cancer; Atypical measles syndrome
ID Measles virus; Hodgkin lymphoma; Lung cancer; Breast cancer; Atypical measles syndrome
AB Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.
C1 [Benharroch, Daniel] Ben-Gurion University of the Negev, Soroka University Medical Center and Faculty of Health Sciences, Departments of Pathology, 1, Itzhak Rager Boulevard, 84101 Beer-Sheva, Israel.
[Ariad, Samuel] Ben-Gurion University of the Negev, Soroka University Medical Center and Faculty of Health Sciences, Departments of OncologyBeer-Sheva, Israel.
[Tadmor, Noa] Ben-Gurion University of the Negev, National Institute for Biotechnology in the Negev, Department of Life SciencesBeer-Sheva, Israel.
[Nalbandyan, Karen] Ben-Gurion University of the Negev, Soroka University Medical Center and Faculty of Health Sciences, Departments of Pathology, 1, Itzhak Rager Boulevard, 84101 Beer-Sheva, Israel.
[Lazarev, Irena] Ben-Gurion University of the Negev, Soroka University Medical Center and Faculty of Health Sciences, Departments of OncologyBeer-Sheva, Israel.
RP Benharroch, D (reprint author), Ben-Gurion University of the Negev, Soroka University Medical Center and Faculty of Health Sciences, Departments of Pathology, 84101 Beer-Sheva, Israel.
EM dbenharroch@yahoo.com
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Wilson KS, Freeland JML, Gallagher A, et al., 2007)Measles virus and classical Hodgkin lymphoma: no evidence for a direct association. Int J Cancer 121:442–447
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 661
EP 666
DI 10.1007/s12253-016-0080-7
PG 6
ER
PT J
AU Yahyapour, Y
Sadeghi, F
Alizadeh, A
Rajabnia, R
Siadati, S
AF Yahyapour, Yousef
Sadeghi, Farzin
Alizadeh, Ahad
Rajabnia, Ramazan
Siadati, Sepideh
TI Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Merkel cell polyomavirus; Human papillomavirus; Oncogenic viruses
ID Esophageal squamous cell carcinoma; Merkel cell polyomavirus; Human papillomavirus; Oncogenic viruses
AB Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 noncancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and noncancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non-cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 × 10−5 ± 2.4 × 10−5 and 6.0 × 10−6 ± 1.3 × 10−5 per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01–6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.
C1 [Yahyapour, Yousef] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Sadeghi, Farzin] Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research CenterBabol, Iran.
[Alizadeh, Ahad] Royan Institute for Reproductive Biomedicine, ACECR, Reproductive Epidemiology Research Center, Department of Epidemiology and Reproductive HealthTehran, Iran.
[Rajabnia, Ramazan] Babol University of Medical Sciences, Infectious Diseases & Tropical Medicine Research CenterBabol, Iran.
[Siadati, Sepideh] Babol University of Medical Sciences, Department of PathologyBabol, Iran.
RP Sadeghi, F (reprint author), Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research Center, Babol, Iran.
EM sadeghifarzin6@gmail.com
CR Lambert R, Hainaut P, 2007, Esophageal cancer: cases and causes, part I). Endoscopy 39(6):550–555
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Al-Haddad S et al., 2014, Infection and esophageal cancer. Ann N YAcad Sci 1325:187–196
Guo F et al., 2012, Human papillomavirus infection and esophageal squamous cell carcinoma: a case-control study. Cancer Epidemiol Biomarkers Prev 21(5):780–785
Yahyapour Y et al., 2013, High-risk and low-risk human papillomavirus in esophageal squamous cell carcinoma at Mazandaran, Northern Iran. Pathol Oncol Res 19(3):385–391
Cao B et al., 2005, LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. Carcinogenesis 26(7):1280–1284
Moens U, Van Ghelue M, Ehlers B, 2014, Are human polyomaviruses co-factors for cancers induced by other oncoviruses? Rev Med Virol 24(5):343–360
Salehi-Vaziri M et al., 2015, Merkel cell polyomavirus and human papillomavirus infections in cervical disease in Iranian women. Arch Virol 160(5):1181–1187
Feng H et al., 2008, Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 667
EP 672
DI 10.1007/s12253-016-0048-7
PG 6
ER
PT J
AU Patocs, A
Lendvai, KN
Butz, H
Liko, I
Sapi, Z
Szucs, N
Toth, G
Grolmusz, KV
Igaz, P
Toth, M
Racz, K
AF Patocs, Attila
Lendvai, K Nikoletta
Butz, Henriett
Liko, Istvan
Sapi, Zoltan
Szucs, Nikolette
Toth, Geza
Grolmusz, K Vince
Igaz, Peter
Toth, Miklos
Racz, Karoly
TI Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pheochromocytoma; Paraganglioma; Germline mutation; Genotype-phenotype
ID Pheochromocytoma; Paraganglioma; Germline mutation; Genotype-phenotype
AB Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare tumors,with heterogeneous genetic background. In up to 30 % of all, apparently sporadic Pheo/PGL cases germline mutations can be identified in one of the 15 genes representing genetic susceptibility for Pheo/PGL. Malignancy is rare but it frequently associates with SDHB mutations. Our aim was to determine the prevalence of germline SDHx, SDHAF2, MAX and TMEM127 mutations in Hungarian patients with apparently sporadic Pheo/PGLs. Mutation screening of the SDHx, SDHAF2, MAX and TMEM127 genes was performed in 82 Hungarian patients with apparently sporadic Pheo/PGL using PCR and bidirectional Sanger sequencing. Disease-causing germline mutations were identified in 11 patients, of which 4 SDHB and 2 TMEM127 mutations were novel. Earlier development of Pheo/PGL, more malignant phenotype and multiple tumors were observed in genetically positive cases especially in those with SDHB mutations. The presence of bilateral or multiple tumors was the most predictive for identification of a pathogenic mutation. Together with cases harboring germline RET, VHL and NF1 mutations, Hungarian patients with Pheo/PGL exhibit a heterogeneousmutation spectrum, indicating that all of the Pheo/PGL susceptibility genes should be tested. Novel genotype-phenotype associations revealed by our study may contribute to improvement of diagnostic approaches and may help to achieve a better clinical follow up for patients with Pheo/PGL.
C1 [Patocs, Attila] Hungarian Academy of SciencesBudapest, Hungary.
[Lendvai, K Nikoletta] Hungarian Academy of SciencesBudapest, Hungary.
[Butz, Henriett] Hungarian Academy of SciencesBudapest, Hungary.
[Liko, Istvan] Hungarian Academy of SciencesBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Szucs, Nikolette] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Toth, Geza] Ferenc Markhot County HospitalEger, Hungary.
[Grolmusz, K Vince] Hungarian Academy of SciencesBudapest, Hungary.
[Igaz, Peter] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Toth, Miklos] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Racz, Karoly] Bionics Innovation CenterBudapest, Hungary.
RP Patocs, A (reprint author), Hungarian Academy of Sciences, Budapest, Hungary.
EM patocs.attila@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 673
EP 679
DI 10.1007/s12253-016-0050-0
PG 7
ER
PT J
AU Farkas, K
Szucs, M
Nyari, AT
AF Farkas, Klaudia
Szucs, Monika
Nyari, Andras Tibor
TI Trends in Gastrointestinal Cancer Mortality Rate in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Cancer of the gallbladder; Esophageal cancer; Gastric cancers; Hepatic cancer; Pancreatic cancer; Mortality rates; Trend; Epidemiology; Hungary
ID Colorectal cancer; Cancer of the gallbladder; Esophageal cancer; Gastric cancers; Hepatic cancer; Pancreatic cancer; Mortality rates; Trend; Epidemiology; Hungary
AB The aim of this study was to investigate the annual death trends for gastrointestinal cancer in Hungary between 1963 and 2012. Data on the numbers of cancer deaths were obtained from the published nationwide population register. Numbers of deaths from esophageal, gastric and colorectal cancer were available during the study period. However, the mortality data for hepatic, pancreatic and gallbladder cancer have been published only since 1979. Joinpoint regression was applied to investigate the annual trends in the rates of cancer mortality. The annual mortality rates of gastric and gallbladder cancer decreased throughout the study period. Furthermore, declines in mortality from esophageal and hepatic cancers have been observed since 1998 and 1995, respectively. However, the rates of colorectal and pancreatic cancer mortality have been increasing in the past few years. Nevertheless, the mortality rates of colorectal and pancreatic cancers have increased in males aged 40–59 years during the study period. Moreover, significantly higher risks of gastrointestinal cancer-related deaths have been observed in males as compared with females except for death related to cancer of the gallbladder. The presented data suggest that the Hungarian mortality rates are particularly high. The detection of gastrointestinal cancers at an early stage would significantly improves the outcome of these malignancies.
C1 [Farkas, Klaudia] University of Szeged, 1st Department of MedicineSzeged, Hungary.
[Szucs, Monika] University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
[Nyari, Andras Tibor] University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
RP Nyari, AT (reprint author), University of Szeged, Department of Medical Informatics, H-6701 Szeged, Hungary.
EM nyari.tibor@med.u-szeged.hu
CR Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al., 2015, Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries, CONCORD-2). Lancet 385(9972):977–1010
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 681
EP 688
DI 10.1007/s12253-016-0052-y
PG 8
ER
PT J
AU Mamede, CA
Guerra, S
Laranjo, M
Santos, K
Carvalho, JM
Carvalheiro, T
Moura, P
Paiva, A
Abrantes, MA
Maia, C
Botelho, FM
AF Mamede, Catarina Ana
Guerra, Sara
Laranjo, Mafalda
Santos, Kathleen
Carvalho, Joao Maria
Carvalheiro, Tiago
Moura, Paulo
Paiva, Artur
Abrantes, Margarida Ana
Maia, J. Claudio
Botelho, Filomena Maria
TI Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human amniotic membrane; Hepatocellular carcinoma; Protein extracts; hAMPE; Oxidative stress; Cell cycle
ID Human amniotic membrane; Hepatocellular carcinoma; Protein extracts; hAMPE; Oxidative stress; Cell cycle
AB The anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor.
C1 [Mamede, Catarina Ana] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Guerra, Sara] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Laranjo, Mafalda] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Santos, Kathleen] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Carvalho, Joao Maria] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Carvalheiro, Tiago] Portuguese Institute of the Blood and Transplantation, Blood and Transplantation Center of CoimbraCoimbra, Portugal.
[Moura, Paulo] Coimbra Hospital and University Centre, Obstetrics ServiceCoimbra, Portugal.
[Paiva, Artur] Coimbra Hospital and University Centre, Clinical Pathology Department, Cytometry Operational Management UnitCoimbra, Portugal.
[Abrantes, Margarida Ana] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
[Maia, J. Claudio] University of Beira Interior, Health Sciences Research Centre, CICS-UBICovilha, Portugal.
[Botelho, Filomena Maria] University of Coimbra, Faculty of Medicine, Biophysics Institute, Azinhaga de Santa Comba - Celas, 3000-548 Coimbra, Portugal.
RP Mamede, CA (reprint author), University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal.
EM ana_mamede@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 689
EP 697
DI 10.1007/s12253-016-0053-x
PG 9
ER
PT J
AU Chen, HI
Tsai, HP
Chen, YT
Tsao, ShCh
Chai, ChY
AF Chen, Hsin-I
Tsai, Hung-Pei
Chen, Yi-Ting
Tsao, Shu-Chuan
Chai, Chee-Yin
TI Autophagy and Apoptosis Play Opposing Roles in Overall Survival of Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autophagy; Apoptosis; Esophageal squamous cell carcinoma
ID Autophagy; Apoptosis; Esophageal squamous cell carcinoma
AB Esophageal cancer is among the most aggressive gastrointestinal tract malignancies, and squamous cell carcinoma is the most common subtype. Although both autophagy and apoptosis involve programmed cell death, autophagy also maintains cell survival by recycling cellular waste. The relationship between autophagy and apoptosis in esophageal squamous cell carcinoma (ESCC) is unclear. Autophagic and apoptotic markers of ESCC were detected by immunohistochemical staining (IHC) in 43 ESCC patients treated during 2007–2011. Chi-square test and Kaplan-Meier method were used to determine how clinicopathological parameters were related to IHC results for LC3B, Beclin-1 and caspase-3 (CASP-3). Correlations among Beclin-1, LC3B, and CASP- 3 were analyzed by Spearman rho. The statistical analyses revealed no clinicopathological parameters that significantly correlated with expressions of Beclin-1, LC3B, and CASP-3. However, low CASP-3 expression and high LC3B expression revealed by IHC were predictors of a poor prognosis. Additionally, LC3B expression had a significant negative correlation with CASP-3 expression. Autophagy is antagonistic to apoptosis and predicts poor overall survival in ESCC.
C1 [Chen, Hsin-I] Kaohsiung Medical University, College of Medicine, Department of Pathology, 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Tsai, Hung-Pei] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Chen, Yi-Ting] Kaohsiung Medical University, College of Medicine, Department of Pathology, 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Tsao, Shu-Chuan] Kaohsiung Medical University, College of Medicine, Department of Pathology, 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Chai, Chee-Yin] Kaohsiung Medical University, College of Medicine, Department of Pathology, 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
RP Chai, ChY (reprint author), Kaohsiung Medical University, College of Medicine, Department of Pathology, 807 Kaohsiung, Taiwan, Republic of China.
EM cychai@kmu.edu.tw
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 699
EP 705
DI 10.1007/s12253-016-0051-z
PG 7
ER
PT J
AU Karadima, LM
Saetta, AA
Chatziandreou, I
Lazaris, CA
Patsouris, E
Tsavaris, N
AF Karadima, L Maria
Saetta, A Angelica
Chatziandreou, Ilenia
Lazaris, C Andreas
Patsouris, Efstratios
Tsavaris, Nikolaos
TI The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.
C1 [Karadima, L Maria] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, Department of Pathophysiology, Oncology Unit, Mikras Asias 75 Street, 11527 Athens, Greece.
[Saetta, A Angelica] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Chatziandreou, Ilenia] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Lazaris, C Andreas] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Patsouris, Efstratios] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Tsavaris, Nikolaos] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, Department of Pathophysiology, Oncology Unit, Mikras Asias 75 Street, 11527 Athens, Greece.
RP Karadima, LM (reprint author), National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, Department of Pathophysiology, Oncology Unit, 11527 Athens, Greece.
EM m_karadima@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 707
EP 714
DI 10.1007/s12253-016-0056-7
PG 8
ER
PT J
AU Sam, S
Reza Sam, M
Esmaeillou, M
Safaralizadeh, R
AF Sam, Sohrab
Reza Sam, Mohammad
Esmaeillou, Mohammad
Safaralizadeh, Reza
TI Effective Targeting Survivin, Caspase-3 and MicroRNA-16-1 Expression by Methyl-3-pentyl-6-methoxyprodigiosene Triggers Apoptosis in Colorectal Cancer Stem-Like Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Survivin; Colorectal cancer stem cells; MicroRNA-16-1; Colorectal cancer; Prodigiosin; Serratia marcescens; Caspase-3; Apoptosis
ID Survivin; Colorectal cancer stem cells; MicroRNA-16-1; Colorectal cancer; Prodigiosin; Serratia marcescens; Caspase-3; Apoptosis
AB Over-expression of the proto-oncogene survivin in colorectal cancer stem cells (CCSCs) is thought to be one the primary causes for therapy failure. It has also been reported that tumor suppressor miR-16-1 is down-regulated in colorectal cancer (CRC) cells. Therefore, the search for new antiproliferative agents which target survivin or miR-16-1 in CCSCs is warranted. Several studies have shown that prodigiosin isolated from cell wall of Serratia marcescens induces apoptosis in different kinds of cancer cells. Here, we investigated the effects of prodigiosin on HCT-116 cells that serve as a model for CRC initiating cells with stem-like cells properties. HCT-116 cells were treated with 100, 200 and 400 nM prodigiosin after which cell number, viability, growth-rate, survivin and miRNA-16-1 expression, caspase- 3 activation and apoptotic rate were evaluated. Prodigiosin decreased significantly growth-rate in a dose-and time-dependent manner. After a 48 h treatment with 100, 200 and 400 nM prodigiosin, growth-rates were measured to be 84.4 ± 9.2 %, 58 ± 6.5 % and 46.3 ± 5.2 %, respectively, compared to untreated cells. We also found that treatment for 48 h with indicated concentrations of prodigiosin resulted in 41 %, 54.5 % and 63 % decrease in survivin mRNA levels and induced 32 %, 48 % and 61 % decrease in survivin protein levels as well as resulted in 128.3 ± 10 %, 178.7 ± 6.1 % and 205 ± 7.6%increase in caspase-3 activation respectively compared to untreated cells. Prodigiosin caused a significant increase in miRNA-16-1 expression at a concentration of 100 nM and treatment with different concentrations of prodigiosin resulted in 2.2- to 3-fold increase in miRNA-16- 1/survivin ratios compared to untreated cells. An increase in number of apoptotic cells ranging from 28.2 % to 86.8 % was also observed with increasing prodigiosin concentrations. Our results provide the first evidence that survivin and miRNA-16- 1 as potential biomarkers could be targeted in CRC initiating cells with stem-like cells properties by prodigiosin and this compound with high pro-apoptotic capacity represents the possibility of its therapeutic application directed against CCSCs.
C1 [Sam, Sohrab] Urmia University, Institute of Biotechnology, Department of Cellular and Molecular BiotechnologyUrmia, Iran.
[Reza Sam, Mohammad] Urmia University, Institute of Biotechnology, Department of Cellular and Molecular BiotechnologyUrmia, Iran.
[Esmaeillou, Mohammad] Urmia University, Institute of Biotechnology, Department of Cellular and Molecular BiotechnologyUrmia, Iran.
[Safaralizadeh, Reza] University of Tabriz, Faculty of Natural Science, Department of Animal BiologyTabriz, Iran.
RP Reza Sam, M (reprint author), Urmia University, Institute of Biotechnology, Department of Cellular and Molecular Biotechnology, Urmia, Iran.
EM s_mohammadreza@yahoo.com;m.sam@urmia.ac.ir
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 715
EP 723
DI 10.1007/s12253-016-0055-8
PG 9
ER
PT J
AU Foda, AMA
El-Hawary, KA
Hamed, H
AF Foda, AlRahman Mohammad Abd
El-Hawary, Kamal Amira
Hamed, Hazem
TI Aberrant Expression of Calretinin, D2–40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal; Mucinous; Calretinin; D2–40; Mesothelin
ID Colorectal; Mucinous; Calretinin; D2–40; Mesothelin
AB CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2–40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2–40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2–40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2–40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2–40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2–40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.
C1 [Foda, AlRahman Mohammad Abd] Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
[El-Hawary, Kamal Amira] Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
[Hamed, Hazem] Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
RP El-Hawary, KA (reprint author), Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
EM amira960@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 725
EP 732
DI 10.1007/s12253-016-0060-y
PG 8
ER
PT J
AU Zhou, P
Sun, L
Liu, D
Liu, Ch
Sun, L
AF Zhou, Peng
Sun, Lixia
Liu, Danfeng
Liu, Changkuo
Sun, Lei
TI Long Non-Coding RNA lincRNA-ROR Promotes the Progression of Colon Cancer and Holds Prognostic Value by Associating with miR-145
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lincRNA-ROR; miR-145; Colon cancer; Oncogene
ID lincRNA-ROR; miR-145; Colon cancer; Oncogene
AB Large intergenic non-coding RNA ribonucleic acids-ROR (lincRNA-ROR) has been reported to exert impacts on the maintenance of induced pluripotent stem cells and embryonic stem cells, and play important roles in human hepatocellular cancer. It contributes to tumorigenesis and metastasis and functions as a competing endogenous RNA (ceRNA) by sponging miR-145 in breast cancer. However, its clinical significance and prognostic value in colon cancer remain unknown. The aim of the present study was to clarify the clinicopathological role and prognostic value of lincRNA-ROR and miR-145 in colon cancer. In the present study, qRT-PCR was performed to measure the expression levels of lincRNA-ROR in colon cancer tissues and cell lines. Then, the clinicopathological significance and prognostic value of lincRNA-ROR were analyzed. LincRNA-ROR expression correlated with pT stage, pN stage, AJCC stage and vascular invasion. Knockdown of lincRNA-ROR restored the expression of miR-145, and had a significant influence on colon cancer cell proliferation, migration and invasion. Patients of the high lincRNA-ROR/low miR-145 group had significantly poorer outcomes than those of the low lincRNA-ROR/high miR-145 group. Taken together, Overexpression of lincRNA-ROR combined with depletion of miR-145 may exert crucial impact on colon cancer prognosis evaluation and treatment.
C1 [Zhou, Peng] The Second People’s Hospital of Wuhu, Department of General Surgery, 259 Jiuhua Middle Road, 241000 Wuhu, China.
[Sun, Lixia] The Second People’s Hospital of Wuhu, Department of General Surgery, 259 Jiuhua Middle Road, 241000 Wuhu, China.
[Liu, Danfeng] The Second People’s Hospital of Wuhu, Department of General Surgery, 259 Jiuhua Middle Road, 241000 Wuhu, China.
[Liu, Changkuo] The Second People’s Hospital of Wuhu, Department of General Surgery, 259 Jiuhua Middle Road, 241000 Wuhu, China.
[Sun, Lei] The Second People’s Hospital of Wuhu, Department of General Surgery, 259 Jiuhua Middle Road, 241000 Wuhu, China.
RP Zhou, P (reprint author), The Second People’s Hospital of Wuhu, Department of General Surgery, 241000 Wuhu, China.
EM doczhoupeng@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 733
EP 740
DI 10.1007/s12253-016-0061-x
PG 8
ER
PT J
AU Popov, MT
Stancheva, G
Goranova, ET
Rangachev, J
Konov, D
Todorov, S
Stoyanov, O
Kaneva, PR
Popova, D
AF Popov, M Todor
Stancheva, Gergana
Goranova, E Teodora
Rangachev, Julian
Konov, Dimitar
Todorov, Spiridon
Stoyanov, Orlin
Kaneva, P Radka
Popova, Diana
TI Strong Correlation Between mRNA Expression Levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in Laryngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIF-1α; HIF-2α; VEGFR1; VEGFR2; MMP2; Flt-1; Flk-1; Laryngeal carcinoma
ID HIF-1α; HIF-2α; VEGFR1; VEGFR2; MMP2; Flt-1; Flk-1; Laryngeal carcinoma
AB The hypoxia that arises due to the rapid proliferation of tumor cells is a fundamental driving force for the canonical pathway of neovascularization. In the current study we report a very strong correlation between mRNA expression levels of HIF-2α (but not HIF-1α), VEGFR-1, VEGFR-2 and MMP2 in ex vivo samples from laryngeal carcinoma. Sixty-three samples from patients with histopathologically verified carcinoma of the larynx were examined in this study. Total RNA was isolated from both normal and tumor fresh frozen tissues of each patient and real-time quantitative PCR reactions were performed. The mRNA expression levels of HIF-1α, HIF-2α, VEGFR1, VEGFR2 and MMP2 were acquired. We found strong positive correlations between mRNA expression levels of HIF-2α and VEGFR-1, rs(98) = .671, p < .0005; HIF-2α and VEGFR-2, rs(98) = .742, p < .0005; HIF-2α and MMP2, rs(98)= .566, p <.0005; VEGFR-1 and VEGFR-2, rs(98) = .791, p < .0005; VEGFR-1 and MMP2, rs(98)= .709, p <.0005; VEGFR-2 and MMP2, rs(98)= .793, p <.0005. Our results provide evidence for the regulatory connection between HIF-2α and VEGFR-1, VEGFR-2 and MMP2 in the light of ETS1/ HIF-2α regulatory axis on a non-in-vitro level in carcinoma tissue, uncover some of the differences between the homologues HIF-1α and HIF-2α and round up and support the results from different experimental models in this field.
C1 [Popov, M Todor] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
[Stancheva, Gergana] Medical University of Sofia, Molecular Medicine CenterSofia, Bulgaria.
[Goranova, E Teodora] Medical University of Sofia, Molecular Medicine CenterSofia, Bulgaria.
[Rangachev, Julian] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
[Konov, Dimitar] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
[Todorov, Spiridon] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
[Stoyanov, Orlin] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
[Kaneva, P Radka] Medical University of Sofia, Molecular Medicine CenterSofia, Bulgaria.
[Popova, Diana] Medical University of Sofia, Department of ENT, blvd., BG-1680 Sofia, Bulgaria.
RP Popov, MT (reprint author), Medical University of Sofia, Department of ENT, BG-1680 Sofia, Bulgaria.
EM popov@todorpopov.com;tmpopov@abv.bg
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 741
EP 746
DI 10.1007/s12253-016-0059-4
PG 6
ER
PT J
AU Prabhu, B
Sivakumar, A
Sundaresan, S
AF Prabhu, Bhoopathy
Sivakumar, Annamalai
Sundaresan, Sivapatham
TI Diindolylmethane and Lupeol Modulates Apoptosis and Cell Proliferation in N-Butyl-N-(4-Hydroxybutyl) Nitrosamine Initiated and Dimethylarsinic Acid Promoted rat Bladder Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Cell proliferation; Diindolylmethane; Lupeol and bladder cancer
ID Apoptosis; Cell proliferation; Diindolylmethane; Lupeol and bladder cancer
AB Bladder cancer has been shown to resist programmed cell death with altered expression of both proapoptotic and anti-apoptotic proteins. To study is to investigate the apoptotic properties of Diindolylmethane (DIM) and Lupeol on N-Butyl-N-(4-hydroxybutyl) Nitrosamine (BBN) initiated and Dimethylarsinic Acid (DMA) promoted urinary bladder cancer. Sixty male Wistar rats were divided into 6 groups. Group I: Control. Group II: Rats were experimentally developed bladder carcinogenesis with BBN and DMA. Group III and IV: DIM and lupeol were administered after BBN treatment for 28 weeks. Group V and VI: DIM and lupeol alone treatment for 36 weeks. All the experimental rats were maintained and euthanized after 36 weeks protocol. Urinary bladder tissues were collected and processed for further investigations. Apoptotis and cell proliferative marker such as Bax, Bcl-2, caspase-3, caspase-9 and PCNA were quantified using immunohistochemical analysis. The Immunohistochemical expression of Bax, Bcl-2, caspase-3, caspase-9 and PCNA were aberrant in BBN+DMA treated tumor group. Administration of DIM and lupeol inhibited the progression of bladder cancer, induced the expression of apoptotic Bax, caspase-3, caspase-9 and inhibited the expression of anti-apoptotic Bcl-2, PCNA in the urinary bladder of rats. Administration of diindolylmethane and lupeol treatment induces apoptosis and cellular proliferation by its anticarcinogenic properties. From our results DIM and lupeol would be the agent or adjunct for the treatment of bladder carcinogenesis.
C1 [Prabhu, Bhoopathy] SRM University, SRM Medical College Hospital Research Centre, Department of Medical Research, Kanchipuram District, 603203 Tamil Nadu, India.
[Sivakumar, Annamalai] SRM University, SRM Medical College Hospital Research Centre, Department of Medical Research, Kanchipuram District, 603203 Tamil Nadu, India.
[Sundaresan, Sivapatham] SRM University, SRM Medical College Hospital Research Centre, Department of Medical Research, Kanchipuram District, 603203 Tamil Nadu, India.
RP Sundaresan, S (reprint author), SRM University, SRM Medical College Hospital Research Centre, Department of Medical Research, 603203 Tamil Nadu, India.
EM drssundaresan@hotmail.com
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Prabhu B, Balakrishnan D, Sundaresan S, 2015, Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl, nitrosamine induced bladder carcinogenesis in experimental rats. Hum Exp Toxicol DOI., DOI 10.1177/0960327115597985
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 747
EP 754
DI 10.1007/s12253-016-0054-9
PG 8
ER
PT J
AU Sarosi, V
Baliko, Z
Smuk, G
Laszlo, T
Szabo, M
Ruzsics, I
Mezosi, E
AF Sarosi, Veronika
Baliko, Zoltan
Smuk, Gabor
Laszlo, Terezia
Szabo, Mariann
Ruzsics, Istvan
Mezosi, Emese
TI The Frequency of EGFR Mutation in Lung Adenocarcinoma and the Efficacy of Tyrosine Kinase Inhibitor Therapy in a Hungarian Cohort of Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NSCLC; Adenocarcinoma; EGFR mutation; TKI
ID NSCLC; Adenocarcinoma; EGFR mutation; TKI
AB In the last decades new therapeutic drugs have been developed for the treatment of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) significantly increase the progression free survival (PFS) of patients with NSCLC carrying epidermal growth factor receptor (EGFR) mutations. This type of lung cancer occurs mainly among non-smoking women and Asian origin. However, the new ESMO guideline recommends EGFR mutation analysis in every patient with NSCLC, because in patients with activating EGFR mutation, TKIs should be considered as first line therapy. In our recent work, we analyzed data of patients with EGFR-mutant adenocarcinoma from January 2009. The number of patients investigated was 446, among them 44 cases were positive for EGFR mutation. The ratio of positive cases was 9.86 % that is lower than the average mutation rate in Europe and much lower than that found in Asia. The exon 19 deletion was detected in 61.4 % of the patients, while L858R point mutation in exon 21 was observed in 34.1 % of them. In one subject, both exon 19 and 21 mutations were present simultaneously. A rare mutation located in exon 21 was found in another patient. TKI therapy was conducted in 38 patients. The disease control rate by TKI therapy was 85.7 %; primary resistance was documented in five subjects. Non-smoking patients with EGFR mutant adenocarcinoma had the highest benefit from TKI treatment. Our data support the recommendation that EGFR mutation status should be defined in all cases of locally advanced or metastatic lung adenocarcinoma.
C1 [Sarosi, Veronika] University of Pecs, I. Department of Internal Medicine, 13 Ifjusag, H-7624 Pecs, Hungary.
[Baliko, Zoltan] University of Pecs, I. Department of Internal Medicine, 13 Ifjusag, H-7624 Pecs, Hungary.
[Smuk, Gabor] University of Pecs, Department of PathologyPecs, Hungary.
[Laszlo, Terezia] University of Pecs, Department of PathologyPecs, Hungary.
[Szabo, Mariann] University of Pecs, I. Department of Internal Medicine, 13 Ifjusag, H-7624 Pecs, Hungary.
[Ruzsics, Istvan] University of Pecs, I. Department of Internal Medicine, 13 Ifjusag, H-7624 Pecs, Hungary.
[Mezosi, Emese] University of Pecs, I. Department of Internal Medicine, 13 Ifjusag, H-7624 Pecs, Hungary.
RP Mezosi, E (reprint author), University of Pecs, I. Department of Internal Medicine, H-7624 Pecs, Hungary.
EM mezosi.emese@pte.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 755
EP 761
DI 10.1007/s12253-016-0063-8
PG 7
ER
PT J
AU An, Ch
Zhang, J
Chu, H
Gu, Ch
Xiao, F
Zhu, F
Lu, R
Shi, H
Zhang, H
Yi, X
AF An, Chaolun
Zhang, Jiajun
Chu, Hongjun
Gu, Chunyan
Xiao, Feng
Zhu, Fengwei
Lu, Rujian
Shi, Hai
Zhang, Hongfei
Yi, Xin
TI Study of Gefitinib and Pemetrexed as First-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gefitinib; Pemetrexed; Advanced non-small cell lung cancer; EGFR mutation
ID Gefitinib; Pemetrexed; Advanced non-small cell lung cancer; EGFR mutation
AB To evaluate the efficacy and safety of a combination regimen of gefitinib and pemetrexed as first-line chemotherapy in advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients. Patients and methods Patients with advanced non-squamous NSCLC harboring asensitive EGFR mutation were included in this study and randomly divided into gefitinib + placebo group and gefitinib + pemetrexed group. Pemetrexed or placebo was administered on day 1 at a dose of 500 mg/m2, and gefitinib was sequentially administered on days 2 ~ 16. This treatment regimen was repeated every 3 weeks until disease progression. All investigators and participants were masked to treatment allocation. The overall response rate (ORR) and disease control rate (DCR) of gefitinib + pemetrexed group were higher than that of gefitinib + placebo group but only the difference of DCR between two groups was statistically significant (P < 0.05). The median progression-free survival (PFS) of gefitinib + placebo group and gefitinib + pemetrexed group were 14.0 months vs. 18 months respectively and the difference was statistically significant (P < 0.05). The 2-year PFS rates of gefitinib + pemetrexed group (20.00 %) was higher than that of gefitinib + placebo group (8.89 %) and the difference was statistically significant (P < 0.05). The median overall survival (OS) of gefitinib + placebo group and gefitinib + pemetrexed group were 32.0 months vs. 34 months respectively and the difference was not statistically significant (P > 0.05). The 3-year OS rates of gefitinib + pemetrexed group (44.44 %) was higher than that of gefitinib + placebo group (35.56 %) but the difference was not statistically significant (P > 0.05). Major grade 3 or 4 hematological toxicities included neutropenia, leukopenia and anemia. The main grade 3 or 4 non-hematological toxicities were infection, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, fatigue, diarrhea and pneumonitis. The difference of toxicities between two groups was not statistically significant (P > 0.05). The combination regimen of gefitinib + pemetrexed used in this study showed a higher ORR and DCR, longer median PFS and acceptable toxicity.
C1 [An, Chaolun] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Zhang, Jiajun] Changhai Hospital of Shanghai, Department of Cardiothoracic SurgeryShanghai, China.
[Chu, Hongjun] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Gu, Chunyan] The Third People’s Hospital of Nantong, Department of PathologyJiangsu, China.
[Xiao, Feng] The Third People’s Hospital of Nantong, Department of PathologyJiangsu, China.
[Zhu, Fengwei] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Lu, Rujian] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Shi, Hai] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Zhang, Hongfei] The Third People’s Hospital of Nantong, Department of Cardiothoracic SurgeryJiangsu, China.
[Yi, Xin] Nantong University, Medical College, Department of Human Anatomy, 19 Qixiu Road, 226001 Nantong, Jiangsu Province, China.
RP Yi, X (reprint author), Nantong University, Medical College, Department of Human Anatomy, 226001 Nantong, China.
EM ntuyixin@foxmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 763
EP 768
DI 10.1007/s12253-016-0067-4
PG 6
ER
PT J
AU Jo, SY
Choi, RM
Song, YS
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Choi, Ryoung Mi
Song, Yong Sang
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of HSPA4 and MED13 in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HSPA4; HSP70; MED13; Mutation; Cancers; Microsatellite instability
ID HSPA4; HSP70; MED13; Mutation; Cancers; Microsatellite instability
AB Frameshift mutation of genes containing mononucleotide repeats is a feature of gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). In the public genome database, we found that human HSPA4 gene encoding a heats hock protein 70 protein (HSP70–4) and MED13 gene had mononucleotide repeats in the coding sequences that could be targets for frameshift mutation in cancers with MSI. HSP70–4 is a member of HSP70 that is known to play a role in cell survival. MED13 is a member of MED genome-wide transcription regulators that function as a regulator for diverse biological processes. In this study, we analyzed the mutations in 79 GCs and 124 CRCs including high MSI (MSI-H) and microsatellite stable/low MSI (MSS/MSIL) cases by single-strand conformation polymorphism analysis and DNA sequencing. We found frameshift mutations of HSPA4 gene in two cancers (one GC and one CRC) and MED13 gene in the other two cancers (one GC and one CRC). The frameshift mutations were deletions of one base (c.2396delA (p.Asn799MetfsX50)) in HSPA4 and (c.2175delA (p.Lys725AsnfsX4)) in MED13. Each of HSPA4 and MED13 mutations were detected in GC with MSI-H (1/34: 2.9 %) and CRC with MSI-H (1/79: 1.3 %), but not in those with MSS. Our data show that unconventional HSPA4 and MED13 genes harbored frameshift mutations in GC and CRC with MSI. These mutations might possibly inactivate their functions and could be a feature of GC and CRC with MSI-H.
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ryoung Mi] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 769
EP 772
DI 10.1007/s12253-016-0070-9
PG 4
ER
PT J
AU Ding, J
Li, C
Tang, J
Yi, Ch
Liu, JY
Qiu, M
AF Ding, Jing
Li, Cong
Tang, Jie
Yi, Cheng
Liu, Ji-Yan
Qiu, Meng
TI Higher Expression of Proteins in IGF/IR Axes in Colorectal Cancer is Associated with Type 2 Diabetes Mellitus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Diabetes mellitus; Insulin-like growth factor; Insulin-like growth factor receptor; Insulin receptor
ID Colorectal cancer; Diabetes mellitus; Insulin-like growth factor; Insulin-like growth factor receptor; Insulin receptor
AB Preexisting type 2 diabetes mellitus (preDM) increases occurrence and mortality of colorectal cancer (CRC). Insulin growth factor (IGF)/insulin receptor (IR) axes play an important role in the development of both diabetes and CRC. We aimed to explore the characteristics of proteins expression in IGF/IR axes in CRC tissues with preDM. Two hundred fifty CRC patients in West China hospital were included in analysis. Among them, 125 patients had history of diabetes matched by 125 CRC without diabetes at a 1:1 ratio. Immunohistochemical staining was used to detect the expression of proteins in IGF/IR axis. More positive expression of IGF-1, IGF-1R and IR were found in CRC group with diabetes than in non-diabetes group. No difference was detected in the expression of IR substrate-1, IR substrate-2, IGF-2, IGF binding protein 3, and mammalian target of rapamycin between two groups. Multivariate analysis showed that diabetes history was associated with all of the expression of IGF-1, IGF-1R and IR, and higher T staging and lymph node metastasis were respectively independent factors of IGF-1 and IGF-1R expression in CRC patients. Besides, IGF-1 expression was positively associated with IGF-1R and IR expression in all CRC tissues, and the association of IGF-1 and IR expression seemed to be closer in diabetes group than in non-diabetes group. Higher expression of IGF-1, IGF-1R and IR proteins in CRC was associated with diabetes, suggesting IGF-1/IR signaling may play a special part in development of CRC in patients with diabetes.
C1 [Ding, Jing] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
[Li, Cong] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
[Tang, Jie] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
[Yi, Cheng] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
[Liu, Ji-Yan] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
[Qiu, Meng] West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, No. 37, Guo Xue Xiang, 610041 Chengdu, Sichuan Province, China.
RP Qiu, M (reprint author), West China Medical School, Sichuan University, Cancer Center, the State Key Laboratory of Biotherapy,West China Hospital, Department of Medical Oncology, 610041 Chengdu, China.
EM qiumeng33@hotmail.com
CR Xu CX, Zhu HH, Zhu YM, 2014, Diabetes and cancer: associations, mechanisms, and implications for medical practice. World J Diabetes 5(3):372–380
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 773
EP 779
DI 10.1007/s12253-016-0065-6
PG 7
ER
PT J
AU Stasikowska-Kanicka, O
Wagrowska-Danilewicz, M
Danilewicz, M
AF Stasikowska-Kanicka, Olga
Wagrowska-Danilewicz, Malgorzata
Danilewicz, Marian
TI Immunohistochemical Study EMT-Related Proteins in HPV-, and EBV-Negative Patients with Sinonasal Tumours
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Slug; Sinonasal inverted papilloma; Sinonasal cancer; E-cadherin; Fibronectin
ID Slug; Sinonasal inverted papilloma; Sinonasal cancer; E-cadherin; Fibronectin
AB Epithelial to mesenchymal transition (EMT) is a biological process in which the epithelial cells, transform to mesenchymal cells via multiple biochemical modifications. Immunohistochemical method was used to examine the expression of EMT-related proteins: Slug, E-cadherin and fibronectin, in 41 cases of sinonasal inverted papilloma (SIP), 33 cases of sinonasal squamous cell carcinoma (SNC), and 22 cases of normal mucosa as a control. In all cases negative viral status was previously confirmed using both in situ hybridization and immunohistochemical method. The immunoexpression of Slug and fibronectin were significantly increased in the SNC group as compared to SIPs and control cases. The immunoexpresssion of Slug was also higher in SIPs as compared to controls. The immunoexpression of Ecadherin was significantly lower in SNCs group as compared with SIPs and controls, but no statistically significant difference in E-cadherin immunoexpression was noted between SIPs and control cases. There were statistically significant negative correlations between immunoexpression of Slug vs E-cadherin, Ecadherin vs fibronectin and positive correlation between Slug vs fibronectin in SNC. Statistically significant correlation between Slug and fibronectin immunoexpression in SIPs was also found. In conclusion, our findings suggest that relationships between Slug, E-cadherin and fibronectin could potentially point to EMT in the sinonasal cancer. Lack of correlation between EMT-related proteins in tested SIPs could reflect a benign nature of those cases.
C1 [Stasikowska-Kanicka, Olga] Medical University of Lodz, Department of NephropathologyLodz, Poland.
[Wagrowska-Danilewicz, Malgorzata] Medical University of Lodz, Department of NephropathologyLodz, Poland.
[Danilewicz, Marian] Medical University of Lodz, Department of NephropathologyLodz, Poland.
RP Stasikowska-Kanicka, O (reprint author), Medical University of Lodz, Department of Nephropathology, Lodz, Poland.
EM olgastasikowska@umed.lodz.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 781
EP 788
DI 10.1007/s12253-016-0068-3
PG 8
ER
PT J
AU Chang, X
Xu, X
Xue, X
Ma, J
Li, Z
Deng, P
Chen, J
Zhang, Sh
Zhi, Y
Dai, D
AF Chang, Xiaojing
Xu, Xiaoyang
Xue, Xiaoying
Ma, Jinguo
Li, Zhenhua
Deng, Peng
Chen, Jing
Zhang, Shuanglong
Zhi, Yu
Dai, Dongqiu
TI NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; NDRG1; Cell differentiation; MMP-9; Metastasis
ID Gastric cancer; NDRG1; Cell differentiation; MMP-9; Metastasis
AB The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p < 0.01), invasion depth (p < 0.05), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), whereas MMP-9 was positive correlated with the degree of tumor cell differentiation (p < 0.01), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), but not correlated with invasion depth (p>0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9.
C1 [Chang, Xiaojing] China Medical University, The Fourth Affiliated Hospital, Department of Gastrointestinal SurgeryShenyang, China.
[Xu, Xiaoyang] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Xue, Xiaoying] Hebei Medical University, The Second Hospital, Department of RadiotherapyShijiazhuang, China.
[Ma, Jinguo] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Li, Zhenhua] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Deng, Peng] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Chen, Jing] China Medical University, The Fourth Affiliated Hospital, Department of Gastrointestinal SurgeryShenyang, China.
[Zhang, Shuanglong] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Zhi, Yu] China Medical University, The Fourth Affiliated Hospital, Cancer CenterShenyang, China.
[Dai, Dongqiu] China Medical University, The Fourth Affiliated Hospital, Department of Gastrointestinal SurgeryShenyang, China.
RP Dai, D (reprint author), China Medical University, The Fourth Affiliated Hospital, Department of Gastrointestinal Surgery, Shenyang, China.
EM daidq63@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 789
EP 796
DI 10.1007/s12253-016-0071-8
PG 8
ER
PT J
AU Riquelme, I
Tapia, O
Espinoza, AJ
Leal, P
Buchegger, K
Sandoval, A
Bizama, C
Araya, CJ
Peek, MR
Roa, CJ
AF Riquelme, Ismael
Tapia, Oscar
Espinoza, A Jaime
Leal, Pamela
Buchegger, Kurt
Sandoval, Alejandra
Bizama, Carolina
Araya, Carlos Juan
Peek, M Richard
Roa, Carlos Juan
TI The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PI3K/AKT/mTOR pathway; Gastric cancer; AGS; MKN28 and MKN45 cell lines
ID PI3K/AKT/mTOR pathway; Gastric cancer; AGS; MKN28 and MKN45 cell lines
AB The PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism and angiogenesis. Emerging evidence has shown that deregulation of this pathway has a role promoting gastric cancer (GC). The aim was to assess the expression of genes involved in this pathway by qPCR in 23 tumor and 23 non-tumor gastric mucosa samples from advanced GC patients, and in AGS, MKN28 and MKN45 gastric cancer cell lines. Results showed a slight overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1, EIF4EBP1 and EIF4E genes, and a slightly decreased PTEN and TSC1 expression. In AGS, MKN28 and MKN45 cells a significant gene overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1 and EIF4E, and a significant repression of PTEN gene expression were observed. Immunoblotting showed that PI3K-β, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p- P70S6K1, 4E-BP1, p-4E-BP1, eIF4E and p-eIF4E proteins were present in cell lines at different levels, confirming activation of this pathway in vitro. This is the first time this extensive panel of 9 genes within PI3K/AKT/mTOR pathway has been studied in GC to clarify the biological role of this pathway in GC and develop new strategies for this malignancy.
C1 [Riquelme, Ismael] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Tapia, Oscar] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Espinoza, A Jaime] Pontificia Universidad Catolica de Chile, Department of Pathology, Marcoleta 377, 7th Floor, 8330024 Santiago, Chile.
[Leal, Pamela] Universidad de La Frontera, Scientific and Technological Bioresource Nucleus (BIOREN), Avenida Alemania 0458, 4810296 Temuco, Chile.
[Buchegger, Kurt] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Sandoval, Alejandra] Pontificia Universidad Catolica de Chile, School of Medicine, UC Centre for Investigational Oncology (CITO), Portugal 61, 8330034 Santiago, Chile.
[Bizama, Carolina] Pontificia Universidad Catolica de Chile, Department of Pathology, Marcoleta 377, 7th Floor, 8330024 Santiago, Chile.
[Araya, Carlos Juan] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Peek, M Richard] Vanderbilt University, School of Medicine, Department of Medicine and Cancer Biology, 2215 Garland Avenue, 37232 Nashville, TN, USA.
[Roa, Carlos Juan] Pontificia Universidad Catolica de Chile, Department of Pathology, Marcoleta 377, 7th Floor, 8330024 Santiago, Chile.
RP Roa, CJ (reprint author), Pontificia Universidad Catolica de Chile, Department of Pathology, 8330024 Santiago, Chile.
EM jcroa@med.puc.cl
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics, 2013. CA Cancer J Clin 63:11–30
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 797
EP 805
DI 10.1007/s12253-016-0066-5
PG 9
ER
PT J
AU Ruiz-Sauri, A
Valencia-Villa, G
Romanenko, A
Perez, J
Garcia, R
Garcia, H
Benavent, J
Sancho-Tello, M
Carda, C
LLombart-Bosch, A
AF Ruiz-Sauri, Amparo
Valencia-Villa, Gerardo
Romanenko, Alina
Perez, Jesus
Garcia, Raul
Garcia, Heydi
Benavent, Jose
Sancho-Tello, Maria
Carda, Carmen
LLombart-Bosch, Antonio
TI Influence of Exposure to Chronic Persistent Low-Dose Ionizing Radiation on the Tumor Biology of Clear-Cell Renal-Cell Carcinoma. An Immunohistochemical and Morphometric Study of Angiogenesis and Vascular Related Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clear-cell renal-cell carcinoma (CCRCC); Chronic persistent low-dose ionizing radiation (CPLDIR); Angiogenesis; Morphometry; Angiogenic factors; Microvessel density (MVD); Immunohistochemistry
ID Clear-cell renal-cell carcinoma (CCRCC); Chronic persistent low-dose ionizing radiation (CPLDIR); Angiogenesis; Morphometry; Angiogenic factors; Microvessel density (MVD); Immunohistochemistry
AB Increased angiogenesis is related to boosted growth and malignancy in carcinomas. "Chronic Persistent Low-Dose Ionizing Radiation" (CPLDIR) exposure increases incidence and aggressive behavior of clear-cell renal-cell carcinoma (CCRCC). The aim was to study the biology of angiogenesis, including microvessel density (MVD), in human clear-cell renalcell carcinomas (CCRCC) originating from a radio-contaminated geographical area (Ukraine) and to compare with similar tumors diagnosed in non-contaminated regions of Europe (Spain, Valencia) and Latin America (Colombia, Barranquilla). MVD was comparatively examined in 124 patients diagnosed with CCRCC from three geographical areas by means of digital micro-imaging and computerized analysis. Additionally, 50 adult normal kidneys were used for controls (autopsy kidneys from Valencia and Barranquilla). Furthermore, an immunohistochemical study of several vascular related growth factors was undertaken using a similar methodology. MVD as well as VEFG are the most discriminating factors associated with an aggressive behavior of CCRCC. Their expression increased in proportion to the level of exposure to chronic low-dose ionizing radiation in Ukrainian patients in the 25 years since the Chernobyl accident substantiated by comparison with the two control groups of renal carcinomas present in non-irradiated areas (Spain and Colombia). No major biological differences relating to angiogenesis appear to exist between the CCRCC diagnosed in two distant geographical areas of the world. HIF-1α expression was similar in all groups, with no statistical significance. Present findings demonstrate the existence of a significant relationship between MVD and VEGF in CCRCC: an increased expression of VEGF is associated with a high level of angiogenesis.
C1 [Ruiz-Sauri, Amparo] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
[Valencia-Villa, Gerardo] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
[Romanenko, Alina] Academy of Medical Sciences of Ukraine, Institute of Urology, Department of PathologyKiev, Ukraine.
[Perez, Jesus] Universidad Libre, Medical SchoolBarranquilla, Colombia.
[Garcia, Raul] Universidad del Norte, Medical SchoolBarranquilla, Colombia.
[Garcia, Heydi] Department of legal medicineBarranquilla, Colombia.
[Benavent, Jose] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
[Sancho-Tello, Maria] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
[Carda, Carmen] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
[LLombart-Bosch, Antonio] University of Valencia, Department of Pathology, Avenida Blasco Ibanez, 15, 46010 Valencia, Spain.
RP Ruiz-Sauri, A (reprint author), University of Valencia, Department of Pathology, 46010 Valencia, Spain.
EM Amparo.Ruiz-Sauri@uv.es
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Romanenko A, Kakehashi A, Morimura K, Wanibuchi H, Wei M, Vozianov A, Fukushima S, 2009, Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident. Carcinogenesis 30(11):1821–1831
Morimura K, Romanenko A, Min W, Salim EI, Kinoshita A, Wanibuchi H, Vozianov A, Fukushima S, 2004, Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster. Oncol Rep 11:881–886
Zablotska LB, Bazyka D, Lubin JH, Gudzenko N, Little MP, Hatch M, Finch S, Dyagil I, Reiss RF, Chumak VV, Bouville A, Drozdovitch V, Kryuchkov VP, Golovanov I, Bakhanova E, Babkina N, Lubarets T, Bebeshko V, Romanenko A, Mabuchi K, 2012, Radiation and the risk of chronic lymphocytic and other Leukemias among Chernobyl cleanup workers. Environ Health Perspect 121(1):59–65
Cote ML, Colt JS, Schwartz KL, Wacholder S, Ruterbusch JJ, Davis F, Purdue M, Graubard BI, Chow W, 2012, Cigarette smoking and renal cell carcinoma risk among black and white Americans: effect modification by hypertension and obesity. Cancer Epidemiol Biomark Prev 21(5):770–779
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Minardi D, Lucarini G, Filosa A, Milanese G, Zizzi A, Di Primio R, Montironi R, Muzzonigro G, 2008, Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up. Int J Immunopathol Pharmacol 21(2):447–455
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http//www.nap.edu/catalog.php?record_id=11340. The National Academies Press. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, 2006).
Vickers MM, Heng DY, 2010, Prognostic and predictive biomarkers in renal cell carcinoma. Target Oncol 5(2):85–94
Lidgren A, Hedberg Y, Grankvist K, Rasmuson T, Vasko J, Ljungberg B, 2005, The expression of hypoxia-inducible factor 1alpha is a favorable independent prognostic factor in renal cell carcinoma. Clin Cancer Res 11:1129–1135
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Meyer M, ClausM, Lepple-Wienhues A,Waltenberger J, Augustin HG, Ziche M, Lanz C, Buttner M, RzihaHJ, Dhio C, 1999, Anovel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2, KDR, but not VEGFR-1, Flt-1, receptor tyrosine kinases. EMBO J 18(2): 363–374
Dordevic G, Matusan-LLijas K, Babarovic E, Hadzisejdic I, Grahova M, Grahov B, Jonjic N, 2009, Hypoxia inducible factor- 1alpha correlates with vascular endothelial growth factor a and C indicating worse prognosis in clear cell renal cell carcinoma. J Exp Clin Cancer Res 28(1):40–47
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 807
EP 815
DI 10.1007/s12253-016-0072-7
PG 9
ER
PT J
AU Mirecka, A
Morawiec, Z
Wozniak, K
AF Mirecka, Alicja
Morawiec, Zbigniew
Wozniak, Katarzyna
TI Genetic Polymorphism of SUMO-Specific Cysteine Proteases − SENP1 and SENP2 in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; SENP1 gene; SENP2 gene; Gene polymorphism; SUMO modification
ID Breast cancer; SENP1 gene; SENP2 gene; Gene polymorphism; SUMO modification
AB SENP proteases take part in post-translational modification of proteins known as sumoylation. They catalyze three distinct processes during sumoylation: processing of SUMO protein, deconjugation of SUMO from the target protein, and chain editing which mentions to the dismantling of SUMO chain. Many proteins that are involved in the basic processes of cells, such as regulation of transcription, DNA repair or cell cycle control, are sumoylated. The aim of these studies was to investigate an association between polymorphic variants (SNPs) of the SENP1 gene (c.1691 + 36C > T, rs12297820) and SENP2 gene (c.902C > A, p.Thr301Lys, rs6762208) and a risk of breast cancer occurrence. We performed a case-control study in 324 breast cancer cases and 335 controls using PCR-RLFP. In the case of the SENP1 gene polymorphism we did not find any association between this polymorphism and breast cancer risk. In the case of SENP2 gene polymorphism we observed higher risk of breast cancer for carriers of the A allele (OR =1.33; 95 % CI 1.04–1.69). Our analysis also showed the genotype C/C (OR =0.67, 95 % CI 0.48–0.93) and the allele C (OR =0.75, 95%CI 0.59–0.69) of this polymorphism decrease a risk of breast cancer.We also checked the distribution of genotypes and frequency of alleles of the SENP1 and SENP2 genes polymorphisms in groups of patients with different hormone receptor status, patients with positive and negative lymph node status and patients with different tumor grade. Odds ratio analysis showed a higher risk of metastases in women with the genotype C/C (OR =2.07, 95 % CI 1.06–4.05) and allele C (OR =2.10 95 % CI 1.10–4.01) of the c.1691 + 36C > T SENP1 gene polymorphism. Moreover, we observed reduced risk in women with the allele T (OR =0.48, 95 % CI 0.25–0.91) in this polymorphic site. In the case of SENP2 gene polymorphism we observed that the A/A genotype correlated with the lack of estrogen receptor (OR =1.94, 95 % CI 1.04–3.62). Our results suggest that the variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence. Further studies are needed to clarify their biological functions in breast cancer.
C1 [Mirecka, Alicja] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Morawiec, Zbigniew] N. Copernicus Hospital, Department of Surgical OncologyLodz, Poland.
[Wozniak, Katarzyna] University of Lodz, Department of Molecular GeneticsLodz, Poland.
RP Wozniak, K (reprint author), University of Lodz, Department of Molecular Genetics, Lodz, Poland.
EM wozniak@biol.uni.lodz.pl
CR Owerbach D, Mckay EM,Yeh ET, GabbayKH, BohrenKM(2005, A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation. Biochem Biophys Res Commun 337:517–520
Bawa-Khalfe T, Yeh ETH, 2010, SUMO losing balance: SUMO proteases disrupt SUMO homeostasis to facilitate cancer development and progression. Genes Cancer 1:748–752
Kim JH, Baek SH, 2009, Emerging roles of desumoylating enzymes. Biochim Biophys Acta 1792:155–162
Itahana Y, Yeh ETH, Zhang Y, 2006, Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2. Mol Cell Biol 26:4675–4689
Watts FZ, 2013, Starting and stopping SUMOylation. What regulates the regulator? Chromosoma 122:451–463
Ihara M, Koyama H, Uchimura Y, Saitoh H, Kikuchi A, 2007, Noncovalent binding of small ubiquitin-related modifier, SUMO, protease to SUMO is necessary for enzymatic activities and cell growth. J Biol Chem 282:16465–16475
Bettermann K, Benesch M, Weis S, Haybaeck J, 2012, SUMOylation in carcinogenesis. Cancer Lett 316:113–125
Jacques C, Baris O, Prunier-Mirebeau D, Savagner F, Rodien P, Rohmer V, Franc B, Guyetant S, Malthiery Y, Reynier P, 2005, Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors. J Clin Endocrinol Metab 90: 2314–2320
Cheng J, Bawa T, Lee P, Gong L, Yeh ET, 2006, Role of desumoylation in the development of prostate cancer. Neoplasia 8:667–676
Bawa-Khalfe T, Cheng J, Lin SH, Ittmann MM, Yeh ETH, 2010, SENP1 induces prostatic intraepithelial neoplasia through multiple mechanisms. J Biol Chem 285:25859–25866
Wang C, Tao W, Ni S, Chen Q, Zhao Z, Ma L, Fu Y, Jiao Z, 2015, Tumor-suppressive microRNA-145 induces growth arrest by targeting SENP1 in human prostate cancer cells. Cancer Sci 106: 375–382
Ma C, Wu B, Huang X, Yuan Z, Nong K, Dong B, Bai Y, Zhu H, Wang W, Ai K, 2014, SUMO-specific protease 1 regulates pancreatic cancer cell proliferation and invasion by targetingMMP- 9. Tumor Biol 35:12729–12735
Wang Q, Xia N, Li T, Xu Y, Zou Y, Zou Y, Fan Q, Bawa-Khalfe T, Yeh ET, Cheng J, 2013, SUMO-specific protease 1 promotes prostate cancer progression and metastasis. Oncogene 32:2493–2498
Xu Y, Li J, Zuo Y, Deng J, Wang LS, Chen GQ, 2011, SUMOspecific protease 1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors. Cancer Lett 309:78–84
Jiang Q-F, Tian Y-W, Shen Q, Xue H-Z, Li K, 2014, SENP2 regulated the stability of β-catenin through WWOX in hepatocellular carcinoma cell. Tumor Biol 35:9677–9682
Tan MY, Mu XY, Liu B, Wang Y, Bao ED, Qiu JX, Fan Y, 2013, SUMO-specific protease 2 suppresses cell migration and invasion through inhibiting the expression of MMP13 in bladder cancer cells. Cell Physiol Biochem 32:542–548
Nait Achour T, Sentis S, Teyssier C, Philippat A, Lucas A, Corbo L, Cavailles V, Jalaguier S, 2014, Transcriptional repression of estrogen receptor α signaling by SENP2 in breast cancer cells. Mol Endocrinol 28:183–196
Goeres J, Chan P-K, Mukhopadhyay D, Zhang H, Raught B, Matunis MJ, 2011, The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex. Mol Biol Cell 22:4868–4882
Hang J, Dasso M, 2002, Association of the human SUMO-1 protease SENP2 with the nuclear pore. J Biol Chem 277:19961–19966
Chow KH, Elgort S, DassoM, PowersMA, Ullman KS, 2014, The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function. Mol Biol Cell 25:160–168
Kumar A, Zhang KYJ, 2015, Advances in the development of SUMO specific protease, SENP, inhibitors. Comput Struct Biotechnol J 13:204–211
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 817
EP 823
DI 10.1007/s12253-016-0064-7
PG 7
ER
PT J
AU Wang, Hy
Zhang, Jj
Zheng, Xy
Liu, Jh
Li, Yw
AF Wang, Hai-ying
Zhang, Jin-jun
Zheng, Xiang-yu
Liu, Jian-hua
Li, Yong-wei
TI Association between IL-6 Gene (−174 & -572 G/C) Polymorphisms and Endometrial Adenocarcinoma Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Interleukin-6; Endometrial adenocarcinoma; Gene polymorphism
ID Interleukin-6; Endometrial adenocarcinoma; Gene polymorphism
AB We aimed to evaluate the association of IL-6 gene polymorphisms at positions of −174 and −572 and predisposition of endometrial adenocarcinoma (EAC) in a Chinese population. EAC patients have remarkably higher frequency of IL-6 -174 CC genotype [odds ratio (OR) =1.56, 95 % confidence interval (CI) =1.07–2.23; P = 0.03], IL-6 -572 CC genotype (OR =1.93, 95%CI =1.17–3.15; P = 0.01) and IL-6 -174 C allele (OR =1.22, 95 % CI =1.03–1.46; P = 0.04) compared with healthy controls. When stratified with FIGO stage, patients with III-IV EAC have a significantly higher frequency of IL-6 -174 CC genotype (OR =1.66, 95%CI =1.06–2.58; P = 0.02) than healthy controls. The CC genotype of IL-6 gene polymorphisms at positions of −174 and −572 may denote potential high risk of EAC.
C1 [Wang, Hai-ying] Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
[Zhang, Jin-jun] Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
[Zheng, Xiang-yu] Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
[Liu, Jian-hua] Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
[Li, Yong-wei] Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
RP Liu, Jh (reprint author), Henan Province Chinese Medicine Hospital, Department of laboratory medicine, 450002 Zhenzhou, China.
EM LIUJianh68@126.com;LIUJianhua593@gmail.com
CR Fowler W, Mutch D, 2008, Management of endometrial cancer. Women's Health, Lond Engl, 4:479–489
Hosoi A, Ueda Y, Shindo M, et al., 2013, Endometrial thickness measured by ultrasonography in postmenopausal patients with endometrial carcinoma has significance, irrespective of histological subtype. Int J Gynecol Cancer 23:1266–1269
Tao QS, Huang HL, Chai Y, et al., 2012, Interleukin-6 up-regulates the expression of interleukin-15 is associated withMAPKs and PI3- K signaling pathways in the human keratinocyte cell line, HaCaT. Mol Biol Rep 39:4201–4205
Bowcock AM, Kidd JR, Lathrop GM, et al., 1988, The human "interferon-beta 2/hepatocyte stimulating factor/interleukin-6" gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8–16
Huang D, Zheng C, Giscombe R, Matell G, Pirskanen R, Lefvert AK, 1999, Polymorphisms at −174 and in the 3′ flanking region of interleukin-6, IL-6, gene in patients with myasthenia gravis. J Neuroimmunol 101:197–200
Bennermo M, Held C, Green F, et al., 2004, Prognostic value of plasma interleukin-6 concentrations and the −174 G > C and −572 G > C promoter polymorphisms of the interleukin-6 gene in patients with acute myocardial infarction treated with thrombolysis. Atherosclerosis 174:157–163
Magalhaes JF, Cortinhas AJ, Albuquerque CM, et al., 2013, Interleukin-6 gene -174G > C and -636G > C promoter polymorphisms and prostate cancer risk. Mol Biol Rep 40:449–455
Xu B, Niu XB, Wang ZD, et al., 2011, IL-6-174G > C polymorphism and cancer risk: a meta-analysis involving 29, 377 cases and 37, 739 controls. Mol Biol Rep 38:2589–2596
Garg R, Wollan M, Galic V, et al., 2006, Common polymorphism in interleukin 6 influences survival of women with ovarian and peritoneal carcinoma. Gynecol Oncol 103:793–796
Nogueira de Souza NC, Brenna SM, Campos F, Syrjanen KJ, Baracat EC, Silva ID, 2006, Interleukin-6 polymorphisms and the risk of cervical cancer. Int J Gynecol Cancer 16:1278–1282
Godarzi EM, Sarvestani EK, Aflaki E, Amirghofran Z, 2011, Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus[J]. Clin Rheumatol 30(2):179–184
Prayong P, Mairiang E, Pairojkul C, et al., 2014, An interleukin-6 receptor polymorphism is associated with opisthorchiasis-linked cholangiocarcinoma risk in Thailand. Asian Pac J Cancer Prev 15: 5443–5447
Liu Z,Wang Z, Xiao Y, Lu Y, Lu Y, 2015, Association between the interleukin-6 gene polymorphisms and renal cancer risk. Immunol Lett 164:125–128
Ebadi N, Jahed M, Mivehchi M, Majidizadeh T, Asgary M, Hosseini SA, 2014, Interleukin-12 and interleukin-6 gene polymorphisms and risk of bladder cancer in the Iranian population. Asian Pac J Cancer Prev 15:7869–7873
Totaro F, Cimmino F, Pignataro P, et al., 2013, Impact of interleukin- 6-174 G > C gene promoter polymorphism on neuroblastoma. PLoS One 8:e76810
Pohjanen VM, Koivurova OP,Makinen JM, et al., 2013, Interleukin 6 gene polymorphism −174 is associated with the diffuse type gastric carcinoma. Genes Chromosom Cancer 52:976–982
Tang S, Yuan Y, He Y, et al., 2014, Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in amale Chinese Han population. HumImmunol 75: 297–301
Delahanty RJ, Xiang YB, Spurdle A, et al., 2013, Polymorphisms in inflammation pathway genes and endometrial cancer risk. Cancer Epidemiol Biomark Prev 22:216–223
Srivani R, Nagarajan B, 2003, A prognostic insight on in vivo expression of interleukin-6 in uterine cervical cancer. Int J Gynecol Cancer 13:331–339
Bellone S,Watts K, Cane’ S et al. High serum levels of interleukin- 6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapyresistant variant of endometrial cancer. Gynecol Oncol 2005; 98: 92–98.
Wei LH, KuoML, Chen CA, et al., 2001, The anti-apoptotic role of interleukin-6 in human cervical cancer ismediated by up-regulation of mcl-1 through a PI 3-K/Akt pathway. Oncogene 20:5799–5809
Grimm C, Watrowski R, Baumuhlner K, et al., 2011, Genetic variations of interleukin-1 and −6 genes and risk of cervical intraepithelial neoplasia. Gynecol Oncol 121:537–541
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 825
EP 829
DI 10.1007/s12253-016-0073-6
PG 5
ER
PT J
AU Pyo, JS
Sohn, HJ
Kang, G
AF Pyo, Jung-Soo
Sohn, Hee Jin
Kang, Guhyun
TI Diagnostic Accuracy of BRAF Immunohistochemistry in Colorectal Cancer: a Meta-Analysis and Diagnostic Test Accuracy Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BRAFV600E immunohistochemistry; Colorectal cancer; Concordance; Diagnostic accuracy; Meta-analysis
ID BRAFV600E immunohistochemistry; Colorectal cancer; Concordance; Diagnostic accuracy; Meta-analysis
AB The aim of this study was to evaluate the concordance between the BRAFV600E mutation test and immunohistochemistry (IHC) and to evaluate the diagnostic accuracy of BRAF IHC for colorectal cancer (CRC) through a systematic review, meta-analysis, and diagnostic test accuracy review. The current study included 1021 CRCs from eight eligible studies. The concordance rates were investigated between BRAF IHC and the mutation test. In addition, diagnostic test accuracy review was conducted and calculated using the value of area under curve (AUC) on the summary receiver operating characteristic (SROC) curve. The positive rate of BRAF IHC was 30.5 % (range; 13.2–66.2 %), and the BRAF mutation was found in 30.2 % (range; 11.7–66.2 %). The overall concordance rate between BRAF IHC and the mutation test was 0.944 (95 % confidence interval (CI) 0.873–0.977). In the BRAF IHC-positive and -negative groups, the concordance rates between BRAF IHC and the mutation test were 0.895 (95 % CI 0.800–0.945) and 0.956 (95 % CI 0.878–0.985), respectively. The pooled sensitivity and specificity were 0.94 (95 % CI 0.91–0.96) and 0.96 (95 % CI 0.95–0.98), respectively. The diagnostic odds ratio was 272.86 (95 % CI 46.11– 1614.88), and the value of AUC on SROC curve was 0.9846. Taken together, our results suggest that BRAF IHC is strongly concordant with the BRAF mutation test and has high diagnostic accuracy in BRAF mutation analysis of CRCs. Further cumulative studies on detailed evaluation criteria are needed before application in daily practice.
C1 [Pyo, Jung-Soo] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 29 Saemunanro, Jongno-gu, 03181 Seoul, South Korea.
[Sohn, Hee Jin] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 29 Saemunanro, Jongno-gu, 03181 Seoul, South Korea.
[Kang, Guhyun] Inje University Sanggye Paik Hospital, Department of PathologySeoul, South Korea.
RP Sohn, HJ (reprint author), Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Pathology, 03181 Seoul, South Korea.
EM jhpath.sohn@samsung.com
CR Pyo JS, Kang G, Kim DH, Chae SW, Park C, Kim K, et al., 2013, Activation of nuclear factor-κB contributes to growth and aggressiveness of papillary thyroid carcinoma. Pathol Res Pract 209:228– 232
Cantwell-Dorris ER, O’Leary JJ, Sheils OM, 2011, BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 10:385–394
Rubinstein JC, Sznol M, Pavlick AC, Ariyan S, Cheng E, Bacchiocchi A, et al., 2010, Incidence of the V600 K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med 8:67
Adackapara CA, Sholl LM, Barletta JA, Hornick JL, 2013, Immunohistochemistry using the BRAF V600E mutation-specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma. Histopathology 63:187–193
Affolter K, Samowitz W, Tripp S, Bronner MP, 2013, BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Genes Chromosom Cancer 52:748–752
Day F, Muranyi A, Singh S, Shanmugam K,Williams D, Byrne D, et al., 2015, A mutant BRAF V600E-specific immunohistochemical assay: correlation with molecular mutation status and clinical outcome in colorectal cancer. Target Oncol 10:99–109
Dvorak K, Aggeler B, Palting J, McKelvie P, Ruszkiewicz A, Waring P, 2014, Immunohistochemistry with the anti-BRAF V600E, VE1, antibody: impact of pre-analytical conditions and concordance with DNA sequencing in colorectal and papillary thyroid carcinoma. Pathology 46:509–517
Lasota J, Kowalik A, Wasag B, Wang ZF, Felisiak-Golabek A, Coates T, et al., 2014, Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach. Am J Surg Pathol 38:1235–1241
Nolan S, Arnason T, Drucker A, Huang WY, 2014, The utility of BRAFV600E mutation-specific antibody for colon cancers with microsatellite instability. Appl Immunohistochem Mol Morphol 22:e8–e13
Roth RM, Hampel H, Arnold CA, Yearsley MM, Marsh WL, Frankel WL, 2015, A modified Lynch syndrome screening algorithm in colon cancer: BRAF immunohistochemistry is efficacious and cost beneficial. Am J Clin Pathol 143:336–343
Sinicrope FA, Smyrk TC, Tougeron D, Thibodeau SN, Singh S, Muranyi A, et al., 2013, Mutation-specific antibody detects mutant BRAFV600E protein expression in human colon carcinomas. Cancer 119:2765–2770
Long GV,Wilmott JS, Capper D, PreusserM, Zhang YE, Thompson JF, et al., 2013, Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol 37:61–65
Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, et al., 2011, BRAF mutations in hairy-cell leukemia. N Engl J Med 364:2305–2315
Pakneshan S, Salajegheh A, Smith RA, Lam AK, 2013, Clinicopathological relevance of BRAF mutations in human cancer. Pathology 45:346–356
Grisham RN, Iyer G, Garg K, DeLair D, Hyman DM, ZhouQ, et al., 2013, BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer 119:548–554
Vaughn CP, Zobell SD, Furtado LV, Baker CL, Samowitz WS, 2011, Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosom Cancer 50:307–312
Toon CW, Walsh MD, Chou A, Capper D, Clarkson A, Sioson L, et al., 2013, BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for lynch syndrome. Am J Surg Pathol 37:1592–1602
Barras D, 2015, BRAF mutation in colorectal cancer: an update. Biomark Cancer 7(Suppl 1):9–12
Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB, 2012, Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair, MMR, gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet 49:151–157
Pyo JS, Sohn JH, Kang G, 2015, BRAF immunohistochemistry using clone VE1 is strongly concordant with BRAF, V600E, mutation test in papillary thyroid carcinoma. Endocr Pathol 26:211– 217
Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A, 2006, Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 6:31
Moses LE, Shapiro D, Littenberg B, 1993, Combining independent studies of a diagnostic test into a summary ROC curve: dataanalytic approaches and some additional considerations. Stat Med 12:1293–1316
Bahreini F, Soltanian AR, Mehdipour P, 2015, A meta-analysis on concordance between immunohistochemistry, IHC, and fluorescence in situ hybridization, FISH, to detect HER2 gene overexpression in breast cancer. Breast Cancer 22:615–625
Pyo JS, Sohn JH, Kim WH, 2016, Concordance rate between HER2 immunohistochemistry and in situ hybridization in gastric carcinoma: systematic review and meta-analysis. Int J BiolMarkers 31:e1–10
Vakiani E, Yaeger R, Brooke S, Zhou Y, Klimstra DS, Shia J, 2015, Immunohistochemical detection of the BRAF V600E mutant protein in colorectal neoplasms. Appl ImmunohistochemMolMorphol 23:438–443
Capper D, Voigt A, Bozukova G, Ahadova A, Kickingereder P, von Deimling A, et al., 2013, BRAF V600E-specific immunohistochemistry for the exclusion of lynch syndrome in MSI-H colorectal cancer. Int J Cancer 133:1624–1630
Kim YH, Choi SE, Yoon SO, Hong SW(2014, A testing algorithm for detection of the B-type Raf kinase V600E mutation in papillary thyroid carcinoma. Hum Pathol 45:1483–1488
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 831
EP 837
DI 10.1007/s12253-016-0077-2
PG 7
ER
PT J
AU Sarsik, B
Doganavsargil, B
Simsir, A
Yazici, A
Pehlivanoglu, B
Cal, C
Sen, S
AF Sarsik, Banu
Doganavsargil, Basak
Simsir, Adnan
Yazici, Ayse
Pehlivanoglu, Burcin
Cal, Cag
Sen, Sait
TI P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cylin-dependent kinase inhibitors; p21; p27; Prognosis; Upper tract urothelial carcinoma; Urinary tract
ID Cylin-dependent kinase inhibitors; p21; p27; Prognosis; Upper tract urothelial carcinoma; Urinary tract
AB p21 and p27 are members of cyclin-dependent kinase family, which function as tumor suppressors and they are involved in development and progression of several malignancies. We investigated their expression in upper urinary tract urothelial carcinoma (UUTUC). Radical nephroureterectomy materials of 34 patients were assessed by immunohistochemistry to evaluate expression of p21 and p27 in UUTUC. Results were correlated with various clinicopathological variables as age, gender, tumor grade and stage, tumor architecture, multifocality, subsequent bladder carcinoma development and clinical outcome. p21 and p27 expression was observed in 52.9 % (n = 18) and 88.2 % (n = 30), respectively. A total of 21 tumors (61.7 %) showed either total loss of p21 expression (n = 16, 47 %) or lower expression (n = 5, 14.7 %). No correlation was found between p21 expression and clinicopathologic variables. Cases showing total loss or lower p27 expression (11.7 % and <25.6 %, respectively) (n = 19, 55.8 %) constituted 67.6 % (n = 23) of the cases totally. This loss or lower p27 expression correlated with a shorter overall survival in both univariate and multivariate analysis (p = 0.039 and p = 0.037, respectively). None of the noninvasive tumors (papillary and nodular tumors) showed loss of p27 (p = 0.016) while 33.3 % of invasive ones showed p27 loss. Noninvasive tumor architecture also correlated with subsequent bladder carcinoma development (p = 0.032) while invasive tumor architecture correlated with advanced stage (T3 and T4) (p = 0.003). p27 is widely expressed in UUTUC, while p21 expression is observed in half of the cases. Loss of p27 expression correlated with tumor architecture and overall survival in UUTUC. However, further research is needed to assess their role in UUTUC.
C1 [Sarsik, Banu] Ege University, Faculty of Medicine, Department of Pathology, Bornova, 35100 Izmir, Turkey.
[Doganavsargil, Basak] Ege University, Faculty of Medicine, Department of Pathology, Bornova, 35100 Izmir, Turkey.
[Simsir, Adnan] Ege University, Faculty of Medicine, Department of UrologyIzmir, Turkey.
[Yazici, Ayse] Mugla University, Education and Research Hospital, Department of PathologyMugla, Turkey.
[Pehlivanoglu, Burcin] Adiyaman University, Training and Research Hospital, Department of PathologyAdiyaman, Turkey.
[Cal, Cag] Ege University, Faculty of Medicine, Department of UrologyIzmir, Turkey.
[Sen, Sait] Ege University, Faculty of Medicine, Department of Pathology, Bornova, 35100 Izmir, Turkey.
RP Sarsik, B (reprint author), Ege University, Faculty of Medicine, Department of Pathology, 35100 Izmir, Turkey.
EM bsarsik@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 839
EP 845
DI 10.1007/s12253-016-0075-4
PG 7
ER
PT J
AU Benezech, S
Chabaud, S
Chambon, F
Dijoud, F
Chotel, F
Marec-Berard, P
AF Benezech, Sarah
Chabaud, Sylvie
Chambon, Fanny
Dijoud, Frederique
Chotel, Franck
Marec-Berard, Perrine
TI Prognostic Value of Vascular Invasion in Pediatric Osteosarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone tumor; Vascular invasion; Osteosarcoma; Prognosis
ID Bone tumor; Vascular invasion; Osteosarcoma; Prognosis
AB Metastatic status, histologic response, and quality of surgical resection are prognostic factors for osteosarcomas. Pathology reports sometimes describe peritumoral vascular invasion on surgical specimens after neoadjuvant chemotherapy but their prognostic significance as an independent parameter has never been reported. The aim of this study was to evaluate how the presence of this peritumoral vascular invasion could influence survival. We retrospectively analyzed histology, demographics, and outcomes of pediatric patients treated for osteosarcoma in our institutions between January 2007 and December 2012. A single pathologist analyzed the resection specimens after neoadjuvant chemotherapy. Fiftyone osteosarcomas were diagnosed over a 6-year period; nine had metastatic disease at diagnosis. Surgery was performed after neoadjuvant chemotherapy in all cases. We identified peritumoral vascular invasion in the surgical specimens in 15 cases. Two-year event-free survival (EFS) was 78 % (CI95%[64;93]) for patients without vascular invasion versus 48 % (CI95% [21;75]) in patients with vascular invasion, and 2-year overall survival (OS) was 94 % (CI95%[86;100]) for those without vascular invasion versus 79%(CI95%[57;100]) for others. Multivariate analysis demonstrated correlation of metastatic status and presence of vascular invasion with survival. The histopathological description of peritumoral vascular invasion in surgical specimens of osteosarcoma after neoadjuvant chemotherapy can be considered a prognostic factor and could indicate modification of the postoperative therapeutic strategy.
C1 [Benezech, Sarah] Institut d’Hematologie et Oncologie Pediatrique, 1 Place Joseph Renaut, 69008 Lyon, France.
[Chabaud, Sylvie] Centre Regional Leon BerardLyon, France.
[Chambon, Fanny] Centre Hospitalier Universitaire de Clermont-FerrandClermont-Ferrand, France.
[Dijoud, Frederique] Hopital Femme-Mere-EnfantBron, France.
[Chotel, Franck] Hopital Femme-Mere-EnfantBron, France.
[Marec-Berard, Perrine] Institut d’Hematologie et Oncologie Pediatrique, 1 Place Joseph Renaut, 69008 Lyon, France.
RP Benezech, S (reprint author), Institut d’Hematologie et Oncologie Pediatrique, 69008 Lyon, France.
EM benezech.sarah@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 847
EP 852
DI 10.1007/s12253-016-0074-5
PG 6
ER
PT J
AU Zhu, L
Liu, J
Shenglin, M
AF Zhu, Lucheng
Liu, Jihong
Shenglin, Ma
TI Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Advanced gastric cancer; Fluoropyrimidine; S-1; Capecitabine; Network meta-analysis
ID Advanced gastric cancer; Fluoropyrimidine; S-1; Capecitabine; Network meta-analysis
AB Fluoropyrimidine-based regimens are the most common treatments in advanced gastric cancer. We used a Bayesian network meta-analysis to identify the optimal fluoropyrimidine-based chemotherapy by comparing their relative efficacy and safety. We systematically searched databases and extracted data from randomized controlled trials, which compared fluoropyrimidine-based regimens as firstline treatment in AGC. The main outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). A total of 12 RCTs of 4026 patients were included in our network metaanalysis. Pooled analysis showed S-1 and capecitabine had a significant OS benefit over 5-Fu, with hazard ratios of 0.90 (95%CI = 0.81–0.99) and 0.88 (95%CI = 0.80–0.96), respectively. The result also exhibited a trend that S-1 and capecitabine prolonged PFS in contrast to 5-Fu, with hazard ratios of 0.84 (95%CI = 0.66–1.02) and 0.84 (95%CI = 0.65–1.03), respectively. Additionally, all the three fluoropyrimidinebased regimens were similar in terms of ORR and grade 3 or 4 AEs. Compared with regimens based on 5-Fu, regimens based on S-1 or capecitabine demonstrated a significant OS improvement without compromise of AEs as first-line treatment in AGC in Asian population. S-1 and capecitabine can be interchangeable according their different emphasis on AEs.
C1 [Zhu, Lucheng] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Liu, Jihong] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
[Shenglin, Ma] Hangzhou First People’s Hospital, Department of Medical Oncology, No.261, Huansha Road, Shangcheng District, 310006 Hangzhou, China.
RP Shenglin, M (reprint author), Hangzhou First People’s Hospital, Department of Medical Oncology, 310006 Hangzhou, China.
EM mashenglin@outlook.com
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Huang D, Ba Y, Xiong J, Xu N, Yan Z, Zhuang Z, Yu Z, Wan H, Zhang Y, Deng T, Zheng R, Guo Z, Hu C, Wang M, Yu Z, Yao Y, Meng J, 2013, A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel +5-fluorouracil for patients with advanced gastric cancer. Eur J Cancer 49(14):2995–3002., DOI 10.1016/j.ejca.2013.05.021
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Sanofi, 2011, Docetaxel and Oxaliplatin in Gastric Cancer. ClinicalTrialsgov:NCT00382720
Cocconi G, DeLisi V, Di Blasio B, 1982, Randomized comparison of 5-FU alone or combined with mitomycin and cytarabine, MFC, in the treatment of advanced gastric cancer. Cancer Treat Rep 66(6): 1263–1266
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Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M, 1997, Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1): 261–267
Ross P, Nicolson M, CunninghamD,Valle J, SeymourM, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A, 2002, Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil, PVI 5-FU, with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20(8):1996–2004
Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S, 2003, Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan clinical oncology group study, JCOG9205). J Clin Oncol 21(1):54–59
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El Sayed YM, SadeeW, 1982, Metabolic activation of ftorafur [R, S-1-(tetrahydro-2-furanyl)-5-fluorouracil]: the microsomal oxidative pathway. Biochem Pharmacol 31(18):3006–3008
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 853
EP 861
DI 10.1007/s12253-016-0078-1
PG 9
ER
PT J
AU Geels, PY
Pijnenborg, MAJ
Gordon, BMB
Fogel, M
Altevogt, P
Masadah, R
Bulten, J
van Kempen, CL
Massuger, FAGL
AF Geels, P Yvette
Pijnenborg, M A Johanna
Gordon, B M Bart
Fogel, Mina
Altevogt, Peter
Masadah, Rina
Bulten, Johan
van Kempen, C Leon
Massuger, F A G Leon
TI L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial carcinoma; Immunohistochemistry; L1CAM; Histopathological diagnosis; Prognostic value; Non-endometrioid
ID Endometrial carcinoma; Immunohistochemistry; L1CAM; Histopathological diagnosis; Prognostic value; Non-endometrioid
AB The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The aim of this study was to determine if L1CAM expression, a recently reported biomarker for aggressive tumor behavior in endometrial carcinoma, was associated with clinicopathological features of EECs. A total of 103 patients diagnosed as EEC at the Radboud University Medical Centre, based on the pathology report were selected. L1CAM status of these tumors was determined, and histologic slides were reviewed by two expert pathologists. L1CAM-positivity was observed in 17 % (18/103). Review of the diagnostic slides revealed that 11 out of these 18 L1CAM-positive tumors (61 %) contained a serous- or mixed carcinoma component that was not initially mentioned in the pathology report. L1CAM-expression was associated with advanced age, poor tumor grade, and lymphovascular space invasion. A worse five year progression free survival rate was observed for patients with L1CAM-positive tumors (55.6 % for the L1CAM-positive group, compared to 83.3 % for the L1CAM-negative group P = 0.01). L1CAM expression carries prognostic value for histologically classified EEC and supports the identification of tumors with a NEEC component.
C1 [Geels, P Yvette] Radboud University Nijmegen, Medical Centre, Department of Obstetrics and GynaecologyNijmegen, The Netherlands.
[Pijnenborg, M A Johanna] Elisabeth-TweeSteden Hospital, Department of Obstetrics and Gynaecology, 5000 Tilburg, LA, The Netherlands.
[Gordon, B M Bart] Radboud University Nijmegen, Medical Centre, Department of Obstetrics and GynaecologyNijmegen, The Netherlands.
[Fogel, Mina] Kaplan Medical Centre, Department of PathologyRehovot, Israel.
[Altevogt, Peter] German Cancer Research Centre, Tumour Immunology Program, D015, 69120 Heidelberg, Germany.
[Masadah, Rina] Hasanuddin University Hospital, Department of PathologyMakassar, Indonesia.
[Bulten, Johan] Radboud University Nijmegen, Medical Centre, Department of PathologyNijmegen, The Netherlands.
[van Kempen, C Leon] Radboud University Nijmegen, Medical Centre, Department of PathologyNijmegen, The Netherlands.
[Massuger, F A G Leon] Radboud University Nijmegen, Medical Centre, Department of Obstetrics and GynaecologyNijmegen, The Netherlands.
RP Pijnenborg, MAJ (reprint author), Elisabeth-TweeSteden Hospital, Department of Obstetrics and Gynaecology, 5000 Tilburg, The Netherlands.
EM H.Pijnenborg@planet.nl
CR Parkin DM, Bray F, Ferlay J, et al., 2005, Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108
Prat J, Gallardo A, Cuatrecasas M, et al., 2007, Endometrial carcinoma: pathology and genetics. Pathology 39(1):72–87
Engelsen IB, Akslen LA, Salvesen HB, 2009, Biologic markers in endometrial cancer treatment. APMIS 117(10):693–707
Geels YP, Pijnenborg JM, van den Berg-van Erp SH, et al., 2012, Endometrioid endometrial carcinoma with atrophic endometrium and poor prognosis. Obstet Gynecol 120(5):1124–1131
Huszar M, Pfeifer M, Schirmer U, et al., 2010, Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas. J Pathol 220(5): 551–561
Zeimet AG, Reimer D, Huszar M, et al., 2013, L1CAM in earlystage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst 105(15):1142–1150
Brummendorf T, Kenwrick S, Rathjen FG, 1998, Neural cell recognition molecule L1: from cell biology to human hereditary brain malformations. Curr Opin Neurobiol 8(1):87–97
Bosse T, Nout RA, Stelloo E, Dreef E, Nijman HW, Jurgenliemk- Schulz IM, Jobsen JJ, Creutzberg CL, Smit VT, 2014, L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer 50(15):2602–2610
FogelM, Gutwein P,Mechtersheimer S, et al., 2003, L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet 362(9387):869–875
Trovik J,Wik E,Werner HM, Krakstad C, Helland H, Vandenput I, Njolstad TS, Stefansson IM, Marcickiewicz J, Tingulstad S, 2013, Staff AC; MoMaTEC study group, Amant F, Akslen LA, Salvesen HB. Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer 49(16):3431–3441
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 863
EP 868
DI 10.1007/s12253-016-0047-8
PG 6
ER
PT J
AU Roncati, L
Barbolini, G
Gatti, MA
Pusiol, T
Piscioli, F
Maiorana, A
AF Roncati, Luca
Barbolini, Giuseppe
Gatti, Morena Antonietta
Pusiol, Teresa
Piscioli, Francesco
Maiorana, Antonio
TI The Uncontrolled Sialylation is Related to Chemoresistant Metastatic Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Invasive ductal carcinoma; Sialic acid; Sialomucins; ST3GAL5 sialyltransferase; Sialidase (neuraminidase); Alcian Blue; DDD-Fast Blue B; Mercury Orange; Elemental microanalysis; Sulphur (S)
ID Breast cancer; Invasive ductal carcinoma; Sialic acid; Sialomucins; ST3GAL5 sialyltransferase; Sialidase (neuraminidase); Alcian Blue; DDD-Fast Blue B; Mercury Orange; Elemental microanalysis; Sulphur (S)
AB Among the scientific communities, there is a convergence of results supporting a direct relationship between dysregulated sialylation and poor prognosis in many human cancers. For this reason, we have retrospectively investigated 169 cases of invasive ductal carcinoma of the breast, coming from female patients aged between 31 and 76 years old. The whole series was subdivided into two prognostic groups: the first group consisted of 138 patients, who showed a post-treatment survival time more than 5 years, while the second group was made up by 31 patients, died within 5 years despite of chemotherapy. All the surgical specimens were fixed in 10%neutral buffered formalin, paraffin embedded and, then, submitted to routinely haematoxylin/eosin staining and to a further histochemical (Alcian Blue, DDD-Fast Blue B, Mercury Orange), immunohistochemical (ST3GAL5 sialyltransferase, Ki67, c-erbB2, ER, PR) and chemico-elemental characterization. In the 31 cases of breast cancer belonging to the second group, an overexpression of sialomucins and sialyltransferases has been detected. Our results lead us to support that in aggressive chemoresistant breast cancers, the altered expression of sialic acid, due to an uncontrolled sialylation, creates an excessive negative charge on cell membranes, which stimulates repulsion between neoplastic cells and their subsequent access into the blood stream. This event implies an earlymetastatization and a rapid disease progression with fatal outcome. The early application of Alcian Blue stain on diagnostic biopsies of breast cancer is able to cheaply reveal the sialomucin accumulations, providing for the disease course.
C1 [Roncati, Luca] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, I-41124 Modena, MO, Italy.
[Barbolini, Giuseppe] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, I-41124 Modena, MO, Italy.
[Gatti, Morena Antonietta] National Research Council, Institute of Science and Technology for CeramicsFaenza, RA, Italy.
[Pusiol, Teresa] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Piscioli, Francesco] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Maiorana, Antonio] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, I-41124 Modena, MO, Italy.
RP Roncati, L (reprint author), University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, I-41124 Modena, Italy.
EM emailmedical@gmail.com
CR Schauer R, 2000, Achievements and challenges of sialic acid research. Glycoconj J 17:485–499
Cazet A, Julien S, Bobowski M, Krzewinski-Recchi MA, Harduin- Lepers A, Groux-Degroote S, et al., 2010, Consequences of the expression of sialylated antigens in breast cancer. Carbohydr Res 345:1377–1383
Christiansen MN, Chik J, Lee L, Anugraham M, Abrahams JL, Packer NH, 2014, Cell surface protein glycosylation in cancer. Proteomics 14:525–546
Miyagi T, Takahashi K, Hata K, Shiozaki K, Yamaguchi K, 2012, Sialidase significance for cancer progression. Glycoconj J 29:567– 577
Gatti AM,Montanari S, 2005, Risk assessment of microparticles and nanoparticles and human health. In: Nalwa HS, ed, Handbook of nanostructured biomaterials and their applications in nanobiotechnology. American Scientific Publishers, Portland, pp. 347–369
Elston CW, Ellis IO, 2002, Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up Histopathology 41:154– 161
Tian Y, Esteva FJ, Song J, Zhang H, 2012, Altered expression of sialylated glycoproteins in breast cancer using hydrazide chemistry and mass spectrometry. Mol Cell Proteomics 11:M111.011403
Kyselova Z, Mechref Y, Kang P, Goetz JA, Dobrolecki LE, Sledge GW, et al., 2008, Breast cancer diagnosis and prognosis through quantitative measurements of serum glycan profiles. Clin Chem 54: 1166–1175
DwekMV, Lacey HA, Leathem AJ, 1998, Breast cancer progression is associated with a reduction in the diversity of sialylated and neutral oligosaccharides. Clin Chim Acta 271:191–202
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 869
EP 873
DI 10.1007/s12253-016-0057-6
PG 5
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutation of MED25, a Transcription Regulator, and its Mutational Heterogeneity in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Makinen N, MehineM, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, Gentile M, Yan J, Enge M, Taipale M,Aavikko M, Katainen R, Virolainen E, Bohling T, Koski TA, Launonen V, Sjoberg J, Taipale J, Vahteristo P, Aaltonen LA, 2011, MED12, the mediator complex subunit 12 gene, Is mutated at high frequency in uterine leiomyomas. Science 334: 252–255.
Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT, 2014, Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet 46:877–880
Poss ZC, Ebmeier CC, Taatjes DJ, 2013, The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48:575–608
Lee HK, Park UH, Kim EJ, Um SJ, 2007, MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. EMBO J 26:3545–3557
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Turunen M, Spaeth JM, Keskitalo S, Park MJ, Kivioja T, Clark AD, Makinen N, Gao F, Palin K, Nurkkala H, Vaharautio A, Aavikko M, Kampjarvi K, Vahteristo P, Kim CA, Aaltonen LA, Varjosalo M, Taipale J, Boyer TG, 2014, Uterine leiomyomalinked MED12 mutations disrupt mediator-associated CDK activity. Cell Rep 7:654–660
CalinGA, Gafa R, TibilettiMG, Herlea V, BecheanuG, Cavazzini L, Barbanti-Brodano G, Nenci I, Negrini M, Lanza G, 2000, Genetic progression in microsatellite instability high, MSI-H, colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes. Int J Cancer 89:230–235
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 875
EP 876
DI 10.1007/s12253-016-0092-3
PG 2
ER
PT J
AU Choi, JE
Kim, SM
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutation of ASPM Gene in Colorectal Cancers with Regional Heterogeneity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L, 2013, Mutational landscape and significance across 12 major cancer types. Nature 502:333–339
Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G, 2014, Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501
Gonzalez-Perez A, Perez-Llamas C, Deu-Pons J, Tamborero D, Schroeder MP, Jene-Sanz A, Santos A, Lopez-Bigas N, 2013, IntOGen-mutations identifies cancer drivers across tumor types. Nat Methods 10:1081–1082
Fish JL, Kosodo Y, Enard W, Paabo S, Huttner WB, 2006, Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci U S A 103:10438–10443
Wang WY, Hsu CC, Wang TY, Li CR, Hou YC, Chu JM, Lee CT, Liu MS, JJ S, Jian KY, Huang SS, Jiang SS, Shan YS, Lin PW, Shen YY, Lee MT, Chan TS, Chang CC, Chen CH, Chang IS, Lee YL, Chen LT, Tsai KK, 2013, A gene expression signature of epithelial tubulogenesis and a role for ASPM in pancreatic tumor progression. Gastroenterology 145:1110–1120
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
Kim MS, JE O, Kim YR, Park SW, Kang MR, Kim SS, Ahn CH, Yoo NJ, Lee SH, 2010, Somatic mutations and losses of expression of microRNA regulation-related genes AGO2 and TNRC6A in gastric and colorectal cancers. J Pathol 221:139–146
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Iwakawa R, Kohno T, Totoki Y, Shibata T, Tsuchihara K, Mimaki S, Tsuta K, Narita Y, Nishikawa R, Noguchi M, Harris CC, Robles AI, Yamaguchi R, Imoto S, Miyano S, Totsuka H, Yoshida T, Yokota J, 2015, Expression and clinical significance of genes frequently mutated in small cell lung cancers defined bywhole exome/ RNA sequencing. Carcinogenesis 36:616–621
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2016
VL 22
IS 4
BP 877
EP 879
DI 10.1007/s12253-016-0108-z
PG 3
ER
PT J
AU Behbahani, DG
Ghahhari, MN
Javidi, AM
Molan, FA
Feizi, N
Babashah, S
AF Behbahani, Dehbashi Golnoush
Ghahhari, Mohammadi Nastaran
Javidi, Amin Mohammad
Molan, Farzi Asghar
Feizi, Neda
Babashah, Sadegh
TI MicroRNA-Mediated Post-Transcriptional Regulation of Epithelial to Mesenchymal Transition in Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cancer; Epithelial to mesenchymal transition; Post-transcriptional regulation; microRNAs
ID Cancer; Epithelial to mesenchymal transition; Post-transcriptional regulation; microRNAs
AB Epithelial to mesenchymal transition (EMT) program participates in tissue repair, embryogenesis and numerous pathological conditions, particularly cancer progression and tumor metastasis. A highly complex and strongly controlled post-transcriptionally regulated network of microRNAs (miRNAs) regulates the EMT process. miRNAs are critical parts of the post-transcriptional regulation of gene expression. A set of miRNAs target multiple components of major signaling pathways and downstream effectors of EMT. miRNAs associated with this process are involved in controlling tumor progression and invasiveness either as oncogenes or as tumor suppressors. Since several miRNAs directly affect EMT-related master regulators, they have been discovered to have the potential to be used as biomarkers or targets in EMT-based pathological conditions such as cancer. Therefore, comprehensive understanding of miRNA-EMT correlation with tumor metastatic spread may provide improvements to diagnostic tools or therapeutics for cancer. This review summarizes our current knowledge about some of these important miRNAs and focuses on their specific roles in regulation of the EMT process in cancer.
C1 [Behbahani, Dehbashi Golnoush] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
[Ghahhari, Mohammadi Nastaran] Pasteur Institute of Iran, Department of BiochemistryTehran, Iran.
[Javidi, Amin Mohammad] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
[Molan, Farzi Asghar] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
[Feizi, Neda] Pasteur Institute of Iran, Laboratory of Influenza ResearchTehran, Iran.
[Babashah, Sadegh] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
RP Babashah, S (reprint author), Tarbiat Modares University, Faculty of Biosciences, Department of Molecular Genetics, Tehran, Iran.
EM s.babashah@modares.ac;sadegh.babashah@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 1
EP 12
DI 10.1007/s12253-016-0101-6
PG 12
ER
PT J
AU Tsai, ShH
Liu, ChA
Huang, KH
Lan, YT
Chen, MH
Chao, Y
Lo, SSh
Li, FYA
Wu, ChW
Chiou, ShH
Yang, MH
Shyr, YM
Fang, WL
AF Tsai, Sheng-Han
Liu, Chien-An
Huang, Kuo-Hung
Lan, Yuan-Tzu
Chen, Ming-Huang
Chao, Yee
Lo, Su-Shun
Li, Fen-Yau Anna
Wu, Chew-Wun
Chiou, Shih-Hwa
Yang, Muh-Hwa
Shyr, Yi-Ming
Fang, Wen-Liang
TI Advances in Laparoscopic and Robotic Gastrectomy for Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Laparoscopic; Robotic; Lymph node dissection; Gastric cancer; Elderly
ID Laparoscopic; Robotic; Lymph node dissection; Gastric cancer; Elderly
AB Robot-assisted gastrectomy has been reported to be a safe alternative to both conventional laparoscopy and the open approach for treating early gastric carcinoma. Currently, there are a limited number of published reports on this technique in the literature. We assessed the current status of robotic and laparoscopic surgery in the treatment of gastric cancer and compared the operative outcomes, learning curves, and oncological outcome of the two approaches. Robotic gastrectomy offers benefits that include increased ease of performing D2 lymph node dissection and reduced blood loss compared with laparoscopic gastrectomy. However, the operative time is longer, and robotic gastrectomy is more costly for the patients. Regarding to the operative and oncological outcomes, there appears to be no significant differences between laparoscopic and robotic gastrectomies after the surgeon overcomes the associated learning curves. Sharing the available knowledge regarding laparoscopic and robotic gastrectomies could shorten these learning curves. For elder patients,minimally invasive surgery that decreases the postoperative recovery time should be considered the preferred treatment. Prospective randomized studies are required to compare the surgical and oncological outcomes among laparoscopic, robotic, and open surgeries for both early and advanced gastric cancer.
C1 [Tsai, Sheng-Han] Cheng Hsin General Hospital, Department of UrologyTaipei, Taiwan, Republic of China.
[Liu, Chien-An] Taipei Veterans General Hospital, Department of RadiologyTaipei, Taiwan, Republic of China.
[Huang, Kuo-Hung] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Lan, Yuan-Tzu] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Chen, Ming-Huang] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Chao, Yee] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Lo, Su-Shun] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Li, Fen-Yau Anna] National Yang-Ming University, School of MedicineTaipei, Taiwan, Republic of China.
[Wu, Chew-Wun] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Chiou, Shih-Hwa] National Yang-Ming University, School of Medicine, Institute of Clinical MedicineTaipei, Taiwan, Republic of China.
[Yang, Muh-Hwa] National Yang-Ming University, School of Medicine, Institute of Clinical MedicineTaipei, Taiwan, Republic of China.
[Shyr, Yi-Ming] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
[Fang, Wen-Liang] Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, No. 201, Sec. 2, Shipai Rd, Beitou District, 11217 Taipei, Taiwan, Republic of China.
RP Fang, WL (reprint author), Taipei Veterans General Hospital, Department of Surgery, Division of General Surgery, 11217 Taipei, Taiwan, Republic of China.
EM s821094@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 13
EP 17
DI 10.1007/s12253-016-0131-0
PG 5
ER
PT J
AU Hosseinpour, S
Mashhadiabbas, F
Ahsaie, GM
AF Hosseinpour, Sepanta
Mashhadiabbas, Fatemeh
Ahsaie, Ghazizadeh Mitra
TI Diagnostic Biomarkers in Oral Verrucous Carcinoma: A Systematic Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Biomarker; Verrucous carcinoma; Oral carcinoma
ID Biomarker; Verrucous carcinoma; Oral carcinoma
AB Oral verrucous carcinoma (OVC), a low-grade variant of oral squamous cell carcinoma (OSCC), is most frequently seen in the oral cavity. No clear etiology has been found for this lesion, but human papilloma virus, chewing betel nuts, and ultraviolet radiation are suggested as probable causes. Differential diagnosis of OVC is challenging for oral pathologists. The aim of this study was to review the molecular-based approaches for differential diagnosis of OVC. An electronic search was conducted in Medline and Scopus from January 2004 to July 2015 limited to English language publications. Published papers on verrucous carcinoma (VC) were found according to the inclusion and exclusion criteria and analyzed qualitatively. Data extraction were performed according to PRISMA statement. A total of 423 articles were reviewed; out of which, 26 articles completely fulfilled the inclusion criteria. Most of the included studies investigated proliferative and apoptotic biomarkers such as p53 and Ki67. No definite conclusion was drawn for cytoskeletal biomarkers due to variability of factors and lack of significant expression. However, it seems that cytokeratin10 (CK 10) can be useful for differentiation of OVC and benign squamous lesions. Among cell surface and extracellular matrix biomarkers tissue biomarkers, matrix metalloproteinase (MMP)-2, −9, CD31 and CD68 seem to be useful for differentiation of OVC and OSCC and glucose transporter-1 (GLUT-1) can help in differentiation of OVC from oral epithelial dysplasia. Differences among OVC, OSCC and normal epithelium in expression profiles of the investigated biomarkers help in their differential diagnosis; although, clinicohistopathological similarities among verrucous hyperplasia, noninvasive OVC and invasive well-differentiated OSCC make the diagnosis difficult. Further studies are required to better differentiate these oral lesions.
C1 [Hosseinpour, Sepanta] Shahid Beheshti University of Medical Sciences, School of Dentistry, Students’ Research OfficeTehran, Iran.
[Mashhadiabbas, Fatemeh] Shahid Beheshti University of Medical Sciences, Dental School, Department of Oral and Maxillofacial Pathology, Daneshjou Boulevard, Evin, 19839 Tehran, Iran.
[Ahsaie, Ghazizadeh Mitra] Shahid Beheshti University of Medical Sciences, School of Dentistry, Students’ Research OfficeTehran, Iran.
RP Mashhadiabbas, F (reprint author), Shahid Beheshti University of Medical Sciences, Dental School, Department of Oral and Maxillofacial Pathology, 19839 Tehran, Iran.
EM Fmashhadiabbas@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 19
EP 32
DI 10.1007/s12253-016-0150-x
PG 14
ER
PT J
AU Reis, H
Bertram, S
Pott, L
Canbay, A
Gallinat, A
Baba, AH
AF Reis, Henning
Bertram, Stefanie
Pott, Leona
Canbay, Ali
Gallinat, Anja
Baba, Andreas Hideo
TI Markers of Hippo-Pathway Activity in Tumor Forming Liver Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hippo-pathway; HCC; Hepatocellular adenoma; FNH; Cirrhosis; Immunohistochemistry
ID Hippo-pathway; HCC; Hepatocellular adenoma; FNH; Cirrhosis; Immunohistochemistry
AB Hepatocellular Carcinoma (HCC) is a lethal cancer worldwide. Recently, the hippo signaling pathway has been implicated in tumorigenesis of HCC and other malignant tumors. Aim of the study was therefore to evaluate the hippo signaling pathway activity and its clinico-pathological associations and crosstalk in different tumor forming hepatocellular lesions (HCC, hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH) and cirrhosis). A tissue micro array (TMA) from paired human tumorous and non-tumorous (NT) tissue samples of HCC (n = 92), HCA (n = 25), FNH (n = 28) and cirrhosis (n = 28; no NT) was constructed. The hippo-pathway related proteins of MST1/2, (nuclear(n)/cytoplasmic(c)) YAP and (phospho(p)) TAZ and interactors as Glypican3, RASSF1a, pAKT, pERK and pP70S6K were evaluated by immunohistochemistry (IHC). Proliferation was assessed by Ki67-IHC and apoptosis by TUNEL-technique. MST1/2- and nYAP-immunoreactivity was associated with lymph node status (p = 0.048, p = 0.001), higher grading (p = 0.012, p = 0.24) and unfavorable relapse-free survival (p = 0.004, p = 0.003). MST1/2, c/nYAP and pTAZ were significantly different between HCC/NT (p < 0.001, p = 0.029, p < 0.001, p < 0.001) and mono−/polyclonal hepatocellular lesions (HCC/HCA vs. FNH/cirrhosis; all p ≤ 0.001). Phospho-TAZ-negativity and nYAP-positivity were almost exclusively and MST1/2 exclusively detected in HCC. MST1/2 correlated with pP70S6K (p = 0.002), pERK (p = 0.042), RASSF1a-IRS (p = 0.002) and GPC3 (p < 0.001) and nYAP with GPC3 (p = 0.025), higher Ki67-indices (p = 0.016) and lower apoptosis rate (p = 0.078). MST1/2 and nYAP are unfavorable prognostic markers associated with an aggressive tumor-phenotype in HCC. Positive nYAP- and negative pTAZ-immunostaining were strong indicators of a monoclonal hepatocellular lesion. The unexpected findings for MST1/2 remain to be elucidated.
C1 [Reis, Henning] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, Hufelandstrasse 55, 45147 Essen, Germany.
[Bertram, Stefanie] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, Hufelandstrasse 55, 45147 Essen, Germany.
[Pott, Leona] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, Hufelandstrasse 55, 45147 Essen, Germany.
[Canbay, Ali] University of Duisburg-Essen, University Hospital of Essen, Department of Gastroenterology and Hepatology, Hufelandstrasse 55, 45147 Essen, Germany.
[Gallinat, Anja] University of Duisburg-Essen, University Hospital of Essen, Department of General, Visceral and Transplantation Surgery, Hufelandstrasse 55, 45147 Essen, Germany.
[Baba, Andreas Hideo] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, Hufelandstrasse 55, 45147 Essen, Germany.
RP Baba, AH (reprint author), University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, 45147 Essen, Germany.
EM Hideo.Baba@uk-essen.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 33
EP 39
DI 10.1007/s12253-016-0079-0
PG 7
ER
PT J
AU Simon, H
Fischer, T
Almasi, A
Fischer, E
AF Simon, Higin
Fischer, Tamas
Almasi, Attila
Fischer, Emil
TI Effects of Mesalazine on Morphological and Functional Changes in the Indomethacin-Induced Inflammatory Bowel Disease (Rat Model of Crohn’s Disease)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Inflammatory bowel disease; Crohn’s disease; Indomethacin; Mesalazine; p-Nitrophenol
ID Inflammatory bowel disease; Crohn’s disease; Indomethacin; Mesalazine; p-Nitrophenol
AB Morphological and functional changes have been investigated in the rat model of Crohn’s disease. The inflammatory bowel disease was induced by indomethacin (1 × 10 mg/kg s.c. for 3 days). Morphological alterations were evaluated by macroscopic scoring system and on the base of histological changes in the small intestine. Functional activities were studied by determination of the intestinal and hepatic elimination of p-Nitrophenol (PNP) and its metabolites (PNP-glucuronide: PNP-G and PNP-sulfate: PNP-S) during the luminal perfusion of PNP. It was found that the indomethacin induced severe macroscopic changes (hyperaemia, petechia, bleeding, erosions, ulcerations) and significant histological alterations in the small intestine of rats which were definitely inhibited by mesalazine (1000 mg/kg by gastric tube for 3 days). Disappearance of PNP from the luminal perfusion solution was diminished by indomethacin which was corrected by administration of mesalazine. Significant depression was found in the luminal appearance of PNP metabolites by giving of indomethacin and these alterations could not be compensated by mesalazine. Hepatic elimination of PNP (biliary excretion of PNP and its metabolites) was decreased definitely by indomethacin which was – at least partly - compensated by mesalazine. The findings of the present study suggest that the indomethacin-induced inflammation in the small intestine represents a useful rat model of Crohn’s disease. Morphological and functional alterations caused by indomethacin can be compensated by mesalazine.
C1 [Simon, Higin] Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, 12 Szigeti utPecs, Hungary.
[Fischer, Tamas] Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, 12 Szigeti utPecs, Hungary.
[Almasi, Attila] Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, 2 Rokus utcaPecs, Hungary.
[Fischer, Emil] Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, 12 Szigeti utPecs, Hungary.
RP Fischer, E (reprint author), Pecsi Tudomanyegyetem, Gyogyszereszeti Intezet, Pecs, Hungary.
EM emil.fischer@aok.pte.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 41
EP 46
DI 10.1007/s12253-016-0069-2
PG 6
ER
PT J
AU Zhao, Chb
Shi, L
Pu, Hh
Zhang, Qy
AF Zhao, Chun-bo
Shi, Lei
Pu, Hai-hong
Zhang, Qing-yuan
TI The Promoting Effect of Radiation on Glucose Metabolism in Breast Cancer Cells under the Treatment of Cobalt Chloride
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radiation; hypoxia; Glucosemetabolism; Hypoxia inducible factors-1α; Cancer cell
ID Radiation; hypoxia; Glucosemetabolism; Hypoxia inducible factors-1α; Cancer cell
AB We aimed to investigate the influence of radiation on hypoxia-treated breast cancers cells and its underlying mechanism. We mimicked the hypoxic response in MCF- 7 cells by the treatment of CoCl2. Meanwhile, hypoxic MCF-7 cells induced by CoCl2 or untreated MCF-7 cells were treated with or without radiation, and then treated with or without hypoxia inducible factors-1α (HIF-1α) inhibitor. Subsequently, glucose update and lactate release rate were determined by commercial kits, as well as the expressions of HIF-1α and the glucose metabolic pathway related genes, including fructose biphoshatase 1 (FBP1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and isocitrate dehydrogenase 2 (IDH20) were detected by western blotting and/or RT-PCR. The results showed that glucose uptake rate and lactate release rate were increased in cells under hypoxia and/or radiation condition compared with untreated cells (p < 0.05), while the addition of HIF-1α inhibitor decreased these rates in hypoxia + radiation treated cells (p < 0.05). In addition, compared with untreated cells, the mRNA and protein levels of HIF-1α were significantly increased under hypoxia and radiation condition (p < 0.05), while which decreased after the addition of HIF-1α inhibitor (p < 0.05). Similar content changing trends (all p < 0.05) were observed in FBP1, IDH2, GLUT1, and LDHA but not HK2. In conclusion, the combination of radiation and hypoxia could promote the glucose metabolism. Furthermore, HIF-1α might inhibit the promoting effect of radiation on glycolysis in hypoxic MCF-7 cells by regulating the glucose metabolic pathway.
C1 [Zhao, Chun-bo] the Third Affiliated Hospital of Harbin Medical University, Department of Radiation Oncology, 150086 Harbin, Heilongjiang Province, China.
[Shi, Lei] the Fourth Affiliated Hospital of Harbin Medical University, Department of Radiation OncologyHarbin, Heilongjiang Province, China.
[Pu, Hai-hong] the Third Affiliated Hospital of Harbin Medical University, Department of Internal Medicine, 150086 Harbin, Heilongjiang Province, China.
[Zhang, Qing-yuan] the Third Affiliated Hospital of Harbin Medical University, Department of Internal Medicine, 150086 Harbin, Heilongjiang Province, China.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 47
EP 53
DI 10.1007/s12253-016-0076-3
PG 7
ER
PT J
AU Amato, M
Perrone, G
Righi, D
Pellegrini, C
Rabitti, C
Di Matteo, F
Crucitti, P
Caputo, D
Coppola, R
Tonini, G
Santini, D
Onetti Muda, A
AF Amato, Michelina
Perrone, Giuseppe
Righi, Daniela
Pellegrini, Claudio
Rabitti, Carla
Di Matteo, Francesco
Crucitti, Pierfilippo
Caputo, Damiano
Coppola, Roberto
Tonini, Giuseppe
Santini, Daniele
Onetti Muda, Andrea
TI HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER2; Gastric cancer; FISH; Immunoistochemistry; Metastatic disease
ID HER2; Gastric cancer; FISH; Immunoistochemistry; Metastatic disease
AB HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5%(K-value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease.
C1 [Amato, Michelina] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
[Perrone, Giuseppe] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
[Righi, Daniela] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
[Pellegrini, Claudio] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
[Rabitti, Carla] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
[Di Matteo, Francesco] University of Rome, Campus Bio-Medico, Endoscopic Unit, Via Alvaro del Portillo, 200Rome, Italy.
[Crucitti, Pierfilippo] University of Rome, Campus Bio-Medico, Department of Surgery, Via Alvaro del Portillo, 200Rome, Italy.
[Caputo, Damiano] University of Rome, Campus Bio-Medico, Department of Surgery, Via Alvaro del Portillo, 200Rome, Italy.
[Coppola, Roberto] University of Rome, Campus Bio-Medico, Department of Surgery, Via Alvaro del Portillo, 200Rome, Italy.
[Tonini, Giuseppe] University of Rome, Campus Bio-Medico, Oncology Unit, Via Alvaro del Portillo, 200Rome, Italy.
[Santini, Daniele] University of Rome, Campus Bio-Medico, Oncology Unit, Via Alvaro del Portillo, 200Rome, Italy.
[Onetti Muda, Andrea] University of Rome, Campus Bio-Medico, Department of Pathology, Via Alvaro del Portillo, 200Rome, Italy.
RP Perrone, G (reprint author), University of Rome, Campus Bio-Medico, Department of Pathology, Rome, Italy.
EM g.perrone@unicampus.it
CR Hultman B, Mahteme H, Sundbom M, et al., 2014, Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy. J Exp Clin Cancer Res 21:110., DOI 10.1186/s13046-014-0110-9
Eckstein N, Roper L, Haas B, et al., 2014, Clinical pharmacology of tyrosine kinase inhibitors becoming generic drugs: the regulatory perspective. J Exp Clin Cancer Res 7:15
Bang YJ, Van Cutsem E, Feyereislova A, et al., 2010, ToGA trial investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer, ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376:687–697
Ajani JA, Bentrem DJ, Besh S, et al., 2013, Gastric cancer, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw 11:531–546
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Tanner M, Hollmen M, Junttila TT, et al., 2005, Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16:273–278
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 55
EP 61
DI 10.1007/s12253-016-0082-5
PG 7
ER
PT J
AU Lopez, F
Sampedro, T
Llorente, LJ
Hermsen, M
Alvarez-Marcos, C
AF Lopez, Fernando
Sampedro, Teresa
Llorente, L Jose
Hermsen, Mario
Alvarez-Marcos, Cesar
TI Alterations of p14ARF, p15INK4b, and p16INK4a Genes in Primary Laryngeal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA methylation; Larynx squamous cell carcinoma; Head and neck squamous cell carcinoma; MS-MLPA; CDKN2B; CDKN2A
ID DNA methylation; Larynx squamous cell carcinoma; Head and neck squamous cell carcinoma; MS-MLPA; CDKN2B; CDKN2A
AB The 9p21 gene cluster, harboring growth suppressive genes p14ARF, p15INK4b, and p16INK4a, is one of the major aberration hotspots in head and neck cancers.We try to elucidate specific aberrations affecting this region, throughout methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 27 laryngeal squamous cell carcinomas and 20 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using and methylation-specific. All samples studied except 3 (11 %) presented losses at 9p21 segment. The most common finding was the small deletion (exon 1α) of the p16INK4a locus (44 %). Deletion of the 9p21 gene cluster was identified in 5 cases (18 %). We only found methylation in 8 samples (30 %) for p15 IK4b-exon 1. Promoter methylation of p14 ARF, p15 IK4b and p16INK4a was not detected in any tumor sample. Methylation-specific polymerase chain reaction confirmed the results. Our data indicate that there may be a subgroup of patients in which epigenetic regulation of 9p21 segment might have little relevance. Nevertheless, MS-MLPA could not be suitable for the study of methylation at this region and further research is required.
C1 [Lopez, Fernando] Department of Otorhinolaryngology and Instituto Universitario de Oncologia del Principado de Asturias, Avenida de Roma, 33011 Oviedo, Asturias, Spain.
[Sampedro, Teresa] Hospital San Agustin, Department of Medical OncologyAviles, Asturias, Spain.
[Llorente, L Jose] Department of Otorhinolaryngology and Instituto Universitario de Oncologia del Principado de Asturias, Avenida de Roma, 33011 Oviedo, Asturias, Spain.
[Hermsen, Mario] Department of Otorhinolaryngology and Instituto Universitario de Oncologia del Principado de Asturias, Avenida de Roma, 33011 Oviedo, Asturias, Spain.
[Alvarez-Marcos, Cesar] Department of Otorhinolaryngology and Instituto Universitario de Oncologia del Principado de Asturias, Avenida de Roma, 33011 Oviedo, Asturias, Spain.
RP Lopez, F (reprint author), Department of Otorhinolaryngology and Instituto Universitario de Oncologia del Principado de Asturias, 33011 Oviedo, Spain.
EM flopez_1981@yahoo.es
CR WorshamMJ, Chen KM, Tiwari N, Pals G, Schouten JP, Sethi S, et al., 2006, Fine-mapping loss of gene architecture at the CDKN2B, p15INK4b), CDKN2A, p14ARF, p16INK4a), andMTAP genes in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 132:409–415
Marcos CA, Alonso-GuervosM, Prado NR, Gimeno TS, Iglesias FD, Hermsen M, et al., 2011, Genetic model of transformation and neoplastic progression in laryngeal epithelium. Head Neck 33:216–224
Laytragoon-Lewin N, Chen F, Castro J, Elmberger G, Rutqvist LE, Lewin F, et al., 2010, DNA content and methylation of p16, DAPK and RASSF1A gene in tumour and distant, normal mucosal tissue of head and neck squamous cell carcinoma patients. Anticancer Res 30:4643–4648
Xing EP, Nie Y, Song Y, Yang GY, Cai YC,Wang LD, et al., 1999, Mechanisms of inactivation of p14ARF, p15INK4b, and p16INK4a genes in human esophageal squamous cell carcinoma. Clin Cancer Res 5:2704–2713
Demokan S, Dalay N, 2011, Role of DNA methylation in head and neck cancer. Clin Epigenetics 2:123–150
Chen K, Sawhney R, KhanM, BenningerMS, Hou Z, Sethi S, et al., 2007, Methylation of multiple genes as diagnostic and therapeutic markers in primary head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 133:1131–1138
Lopez F, Sampedro T, Llorente JL, Dominguez F, Hermsen M, Suarez C, et al., 2014, Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous cell carcinoma. Oral Oncol 50:291–297
Lopez F, Llorente JL, Garcia-Inclan C, Alonso-Guervos M, Cuesta- Albalad MP, Fresno MF, et al., 2011, Genomic profiling of sinonasal squamous cell carcinoma. Head Neck 33:145–153
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Danahey DG, Tobin EJ, Schuller DE, Bier-Laning CM, Weghorst CM, Lang JC, 1999, p16 Mutation frequency and clinical correlation in head and neck cancer. Acta Otolaryngol 119:285–288
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Wong TS,ManMWL, LamAKY,Wei WI, KwongYL,Yuen APW, 2003, The study of p16 and p15 genemethylation in head and neck squamous cell carcinoma and their quantitative evaluation in plasma by real-time PCR. Eur J Cancer 39:1881–1887
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 63
EP 71
DI 10.1007/s12253-016-0083-4
PG 9
ER
PT J
AU Yang, X
Liu, Y
Mani, H
Olson, J
Clawson, G
Caruso, C
Bruggeman, R
Varlotto, MJ
Zander, SD
Rassaei, N
AF Yang, Xuebin
Liu, Yongjun
Mani, Haresh
Olson, Jeffrey
Clawson, Gary
Caruso, Carla
Bruggeman, Richard
Varlotto, M John
Zander, S Dani
Rassaei, Negar
TI Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Epithelial-to-mesenchymal transition; Diabetes
ID Non-small cell lung cancer; Epithelial-to-mesenchymal transition; Diabetes
AB A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) andwithout (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-β), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E-cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-β, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. Ncadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC.
C1 [Yang, Xuebin] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Liu, Yongjun] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Mani, Haresh] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Olson, Jeffrey] Penn State College of MedicineHershey, PA, USA.
[Clawson, Gary] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Caruso, Carla] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Bruggeman, Richard] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Varlotto, M John] University of Massachusetts, Medical School, Department of Radiation OncologyWorcester, MA, USA.
[Zander, S Dani] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
[Rassaei, Negar] Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 500 University Drive, 17033-0850 Hershey, PA, USA.
RP Rassaei, N (reprint author), Penn State Hershey Medical center, Department of Pathology and Laboratory Medicine, 17033-0850 Hershey, USA.
EM nrassaei@hmc.psu.edu
CR El-Sherif A, Fernando HC, Santos R, Pettiford B, Luketich JD, Close JM, et al., 2007, Margin and local recurrence after sublobar resection of non-small cell lung cancer. Ann Surg Oncol 14(8): 2400–2405
Martini N, Bains MS, Burt ME, Zakowski MF, McCormack P, Rusch VW, et al., 1995, Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109(1):120–129
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Schmalhofer O, Brabletz S, Brabletz T, 2009, E-cadherin, betacatenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev 28(1–2):151–166
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 73
EP 77
DI 10.1007/s12253-016-0086-1
PG 5
ER
PT J
AU Thakral, G
Wey, A
Rahman, M
Fang, R
Lum, Ch
AF Thakral, Gaurav
Wey, Andrew
Rahman, Mobeen
Fang, Rui
Lum, Christopher
TI Agreement of Different Methods for Tissue Based Detection of HER2 Signal in Invasive Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Fish; Altman bland; HER2 Recptor; Breast neoplasms/diagnosis; Breast neoplasms/treatment
ID Fish; Altman bland; HER2 Recptor; Breast neoplasms/diagnosis; Breast neoplasms/treatment
AB Breast cancer is the second leading cause of cancer mortality amongst American women. The HER2 gene encodes a cell surface receptor that affects cell proliferation and has been recognized as a diagnostic factor in treatment selection for invasive breast cancer. Examine accuracy in HER2 detection between manual count, computer assisted, and automated tiling algorithm. 42 randomly selected invasive breast cancer specimens were enumerated by fluorescence in situ hybridization (FISH)for HER2 and CEP17 markers using the Vysis HER2 assay (AbbotLaboratory, North Chicago, IL). Specimens were tested using three methods: Manual, computer assisted nuclei selection (Tissue FISH MetaSystems, Newton, MA), and automated enumeration (MetaSystems, Newton, MA). The greatest bias and widest agreement limits for HER2 and CEP17 were seen in Automatic versus Manual, the gold standard. HER2 values greater than 6 possessed the greatest bias and widest agreement limits. CEP17 comparison showed similar bias and agreement limits for each comparison. Kappa values indicated good agreement for all methods although Tissue FISH and Manual possessed better agreement. Higher agreement at lower HER2 & CEP17 count maybe due to fewer chromosomal aberrations, in which selection of field of views has less variation between methods. Alternatively, increased background signals seen in polyploidy may be responsible for the variations in signal count. Manual and Tissue FISH demonstrated good agreement amongst by both Altman Bland and Cohen’s Kappa. While the automatic method has good agreement at lower HER2, the sharp increase in variability at higher HER2 counts illustrates a limitation of the automatic method.
C1 [Thakral, Gaurav] University of Hawaii and Kuakini Medical CenterHonolulu, HI, USA.
[Wey, Andrew] University of Hawaii and Kuakini Medical CenterHonolulu, HI, USA.
[Rahman, Mobeen] University of Hawaii and Kuakini Medical CenterHonolulu, HI, USA.
[Fang, Rui] University of Hawaii and Kuakini Medical CenterHonolulu, HI, USA.
[Lum, Christopher] University of Hawaii and Kuakini Medical CenterHonolulu, HI, USA.
RP Thakral, G (reprint author), University of Hawaii and Kuakini Medical Center, Honolulu, USA.
EM gthakral@hawaii.edu
CR Humphrey LL, Helfand M, Chan BK, Woolf SH, 2002, Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137(5 Part 1): 347–360
Heim S, Mitelman F., 2011, Cancer cytogenetics: chromosomal and molecular genetic abberations of tumor cells: John Wiley & Sons
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al., 2013, Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol Off J Am Soc Clin Oncol 31(31):3997–4013., DOI 10.1200/JCO.2013.50.9984
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al., 2005, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16): 1659–1672
Hanna WM, Ruschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY, et al., 2014, HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol: an official journal of the United States and Canadian Academy of Pathology, Inc. 27(1):4–18., DOI 10.1038 /modpathol.2013.103
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL, 1987, Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182
Hicks DG, Tubbs RR., 2005, Assessment of the HER2 status in breast cancer by fluorescence in situ hybridization: a technical review with interpretive guidelines. Hum Pathol 36(3):250–261., DOI 10.1016/j.humpath.2004.11.010.
Furrer D, Jacob S, Caron C, Sanschagrin F, Provencher L, Diorio C., 2013, Validation of a new classifier for the automated analysis of the human epidermal growth factor receptor 2, HER2, gene amplification in breast cancer specimens. Diagn Pathol 8:17., DOI 10.1186 /1746-1596-8-17
Myles P, Cui J. I., 2007, Using the bland–Altman method to measure agreement with repeated measures. Br J Anaesth 99(3):309–311.
Bland JM, Altman D., 1986, Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 327(8476):307–310.
Viera AJ, Garrett JM., 2005, Understanding interobserver agreement: the kappa statistic. Fam Med 37(5):360–363.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al., 2014, Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138(2):241–256., DOI 10.5858/arpa.2013-0953-SA
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 79
EP 84
DI 10.1007/s12253-016-0091-4
PG 6
ER
PT J
AU Forghanifard, MM
Khales, AS
Farshchian, M
Rad, A
Homayouni-Tabrizi, M
Abbaszadegan, RM
AF Forghanifard, Mahdi Mohammad
Khales, Ardalan Sima
Farshchian, Moein
Rad, Abolfazl
Homayouni-Tabrizi, Masoud
Abbaszadegan, Reza Mohammad
TI Negative Regulatory Role of TWIST1 on SNAIL Gene Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epithelial-mesenchymal transition (EMT); TWIST1; SNAIL; ESCC cell line
ID Epithelial-mesenchymal transition (EMT); TWIST1; SNAIL; ESCC cell line
AB Epithelial-mesenchymal transition (EMT) is crucial for specific morphogenetic movements during embryonic development as well as pathological processes of tumor cell invasion and metastasis. TWIST and SNAIL play vital roles in both developmental and pathological EMT. Our aim in this study was to investigate the functional correlation between TWIST1 and SNAIL in human ESCC cell line (KYSE-30). The packaging cell line GP293Twas cotransfected with either control retroviral pruf-IRES-GFP plasmid or pruf-IRES-GFPhTWIST1 and pGP plasmid. The KYSE-30 ESCC cells were transduced with produced viral particles and examined with inverted fluorescence microscope. DNA was extracted from transduced KYSE-30 cells and analyzed for copy number of integrated retroviral sequences in the target cell genome. The concentration of retroviral particles was determined by Realtime PCR. After RNA extraction and cDNA synthesis, the mRNA expression of TWIST1 and SNAIL was assessed by comparative real-time PCR amplification. Ectopic expression of TWIST1 in KYSE-30, dramatically reduces SNAIL expression. Retroviral transduction enforced TWIST1 overexpression in GFP-hTWIST1 nearly 9 folds in comparison with GFP control cells, and interestingly, this TWIST1 enforced expression caused a − 7 fold decrease of SNAIL mRNA expression in GFP-hTWIST1 compared to GFP control cells. Inverse correlation of TWIST1 and SNAIL mRNA levels may introduce novel molecular gene expression pathway controlling EMT process during ESCC aggressiveness and tumorigenesis. Consequently, these data extend the spectrum of biological activities of TWIST1 and propose that therapeutic repression of TWIST1 may be an effective strategy to inhibit cancer cell invasion and metastasis.
C1 [Forghanifard, Mahdi Mohammad] Sabzevar University of Medical Sciences, Cellular and Molecular Research CenterSabzevar, Iran.
[Khales, Ardalan Sima] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, Bu-Ali square, 9196773117 Mashhad, Iran.
[Farshchian, Moein] ACECR-Khorasan Razavi Branch, Molecular Medicine Research DepartmentMashhad, Iran.
[Rad, Abolfazl] Sabzevar University of Medical Sciences, Cellular and Molecular Research CenterSabzevar, Iran.
[Homayouni-Tabrizi, Masoud] Islamic Azad University, Mashhad Branch, Department of Biochemistry and BiophysicsMashhad, Iran.
[Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, Bu-Ali square, 9196773117 Mashhad, Iran.
RP Abbaszadegan, RM (reprint author), Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
EM abbaszadeganmr@mums.ac.ir
CR Gavert N, Ben-Ze'ev A, 2008, Epithelial-mesenchymal transition and the invasive potential of tumors. Trends MolMed 14(5):199–209
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Batlle E et al., 2000, The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2(2):84–89
Cano A et al., 2000, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2(2):76–83
Hajra KM, Chen DY, Fearon ER, 2002, The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 62(6): 1613–1618
Eger A, A.K., Sonderegger S, et al., 2005, DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 24:2375–2385
Comijn J, Berx G, A. A e, Vermassen P, 2001, The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 7:1267–1278
Yang J et al., 2004, Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939
Sosic D, EN O, 2003, A new twist on twist–modulation of theNFkappa B pathway. Cell Cycle 2:76–78
Maestro R et al., 1999, Twist is a potential oncogene that inhibits apoptosis. Genes Dev 13:2207–2217
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Hong J et al., 2011, Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res 71(11):3980–3990
Castanon I et al., 2001, Dimerization partners determine the activity of the twist bHLH protein during drosophila mesoderm development. Development 128(16):3145–3159
de Herreros AG et al., 2010, Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia 15(2):135–147
Peinado H, Olmeda D, CanoA, 2007, Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7(6):415–428
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Ardalan Khales S et al., 2015, SALL4 as a new biomarker for early colorectal cancer. J Cancer Res Clin Oncol 141(2):229– 235
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Castanon I, Baylies MK, 2002, A twist in fate: evolutionary comparison of twist structure and function. Gene 287(1–2):11–22
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Lander R et al., 2013, Interactions between twist and other core epithelial–mesenchymal transition factors are controlled by GSK3- mediated phosphorylation. Nat Commun 4:1542
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 85
EP 90
DI 10.1007/s12253-016-0093-2
PG 6
ER
PT J
AU Kumari, S
Tewari, Sh
Husain, N
Agarwal, A
Pandey, A
Singhal, A
Lohani, M
AF Kumari, Swati
Tewari, Shikha
Husain, Nuzhat
Agarwal, Akash
Pandey, Anshuman
Singhal, Ashish
Lohani, Mohtashim
TI Quantification of Circulating Free DNA as a Diagnostic Marker in Gall Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating free DNA; Gall bladder cancer; Real time PCR (qPCR); DNA quantification
ID Circulating free DNA; Gall bladder cancer; Real time PCR (qPCR); DNA quantification
AB Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a "liquid biopsy" in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of β-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p = <0.001). The cfDNA level was significantly associated with TNM stage, lymph node involvement and jaundice (0.002, 0.027, and 0.041, respectively). Area under curve of ROC analysis for cancer group versus healthy and cholecystitis group was 1.00 and 0.983 with sensitivity of 100 %, 88.24 % and specificity of 100 % respectively. Quantitative analysis of cfDNA may distinguish cholecystitis and gall bladder carcinoma and may serve as new diagnostic, noninvasive marker adjunct to imaging for the diagnosis of GBC.
C1 [Kumari, Swati] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, India.
[Tewari, Shikha] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, India.
[Husain, Nuzhat] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, India.
[Agarwal, Akash] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Surgical Oncology, 226010 Lucknow, India.
[Pandey, Anshuman] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Gastrosurgery, 226010 Lucknow, India.
[Singhal, Ashish] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Surgical Oncology, 226010 Lucknow, India.
[Lohani, Mohtashim] Integral University, Department of Biosciences, 226026 Lucknow, India.
RP Husain, N (reprint author), Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, India.
EM drnuzhathusain@hotmail.com
CR Mishra S, Chaturvedi A, Mishra NC, Sharma ID, 2013, Carcinoma of the gallbladder. The Lancet Oncology 4:167–176
Hamdani NS, Qadri SK, Aggarwalla R, Bhartia VK, Chaudhuri S, Debakshi S, Baig SJ, Pal NK, 2013, Clinicopathological Study of Gall Bladder Carcinoma with Special Reference to Gallstones: Our 8-year Experience from Eastern India. Asian Pacific J Cancer Prev 13(11):5613–5617
Goldin RD, Roa JC, 2009, Gallbladder cancer: a morphological and molecular update. Histopathology 55:218–229
Kapoor VK, Michael AJ Mc, 2003, Gallbladder cancer: An ‘Indian’ disease. Natl Med J India 4:16.
Peng HH, Zhang YD, Gong LS, Liu WD, Zhang Y, 2013, Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma. Onco Targets Ther 6: 1625–1630.
Liu TY, Tan ZJ, Jiang L, JF G, XSW, Cao Y, LiML, KJW, Liu YB, 2013, Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells. Cancer Cell Int 13:6
Stroun M, Maurice P, Vasioukhin V, Lyautey J, Lederry C, Lefort F, 2000, The origin and mechanism of circulating DNA. Ann N Y Acad Sci 906:161–168
Ellinger J, Bastian PJ, Haan KI, Heukamp LC, Buettner R, Fimmers R, Mueller SC, Von Ruecker A, 2008, Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators. Int J Cancer 122(1):138–143
Sozzi G, Conte D, Mariani L, 2001, Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res 61:4675–4678
Umetani N, Kim J, Hiramatsu S, 2006, Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats. Clin Chem 52: 1062–1069.
Trejo-Becerril C, Perez-Cardenas E, Trevino-Cuevas H, 2003, Circulating nucleosomes and response to chemotherapy: an in vitro, in vivo and clinical study on cervical cancer patients. Int J Cancer 104:663–668
Chang HW, Lee SM, Goodman SN, 2002, Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer. J Natl. Cancer Inst 94:1697–1703
Gal S, Fidler C, Lo YMD, Taylor M, Han C, Moore J, Harris AL, Wainscoat JS, 2004, Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR. Br J Cancer 90:1211–1215
Ellinger J,Wittkamp V, Albers P, 2009, Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J Urol 181:363–371
Ellinger J, Bastian PJ, Ellinger N, 2008, Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer: a prognostic entity. Cancer Lett 264:274–280
Altimari A, Grigioni AD, Benedettini E, 2008, Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer. Am. J Clin Pathol 129:756–762
Sai S, Ichikawa D, Tomita H, Ikoma D, Tani N, Ikoma H, Kikuchi S, Fujiwara H, Ueda Y, Otsuji E, 2007, Quantification of Plasma Cell-free DNA in Patients with Gastric Cancer. Anticancer Res 27: 2747–2752
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 91
EP 97
DI 10.1007/s12253-016-0087-0
PG 7
ER
PT J
AU Groeger, S
Howaldt, HP
Raifer, H
Gattenloehner, S
Chakraborty, T
Meyle, J
AF Groeger, Sabine
Howaldt, Hans-Peter
Raifer, Hartmann
Gattenloehner, Stefan
Chakraborty, Trinad
Meyle, Joerg
TI Oral Squamous Carcinoma Cells Express B7-H1 and B7-DC Receptors in Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinomas; B7-H1; B7-Dc; In vivo; Immune evasion
ID Oral squamous cell carcinomas; B7-H1; B7-Dc; In vivo; Immune evasion
AB B7-H1 and B7-DC ligands are members of the B7 family with important regulatory functions in cell-mediated immune response. Both receptors are ligands of the programmed death receptor PD-1. B7-H1 expression has been detected in the majority of human carcinomas in vivo. B7- H1 mediated signals are able to negatively regulate activated T cell functions and survival, and enable tumor cells to overcome host response. The aim of this study was to investigate the expression of B7-H1 and B7-DC proteins in oral squamous cell carcinomas (OSCC) in vivo. Tissues from 15 samples were cryo-sected and following histological routine staining (HE), incubated with antibodies against human B7-H1 and B7-DC. Immuno-staining of pan-cytokeratin was performed to ascertain the epithelial origin of the tissue and CK 19 to demonstrate the proliferating stage. Confocal laser scanning microscopy confirmed the presence of both B7-H1 and B7- DC in all 15 OSCC. The B7-H1 and B7-DC staining was located in areas of the tissue that were identified as cancerous lesions in the previously stained HE sections before. Staining with Pan-CK and CK19 provided evidence for the epithelial origin and the proliferating stage of the tissue. The in vivo expression of the B7-H1 and B7-DC receptors in oral squamous cell carcinomas suggest that general mechanisms for immune evasion of tumors are also found in OSCC.
C1 [Groeger, Sabine] Justus-Liebig-University, Department of Periodontology, Schlangenzahl 14, 35392 Giessen, Germany.
[Howaldt, Hans-Peter] Justus-Liebig-University, Oral and Maxillofacial SurgeryGiessen, Germany.
[Raifer, Hartmann] Phillips University, Institute for Medical Microbiology and HygieneMarburg, Germany.
[Gattenloehner, Stefan] Justus-Liebig-University, Institute for PathologyGiessen, Germany.
[Chakraborty, Trinad] Justus-Liebig-University, Institute for Medical MicrobiologyGiessen, Germany.
[Meyle, Joerg] Justus-Liebig-University, Department of Periodontology, Schlangenzahl 14, 35392 Giessen, Germany.
RP Groeger, S (reprint author), Justus-Liebig-University, Department of Periodontology, 35392 Giessen, Germany.
EM Sabine.E.Groeger@dentist.med.uni-giessen.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 99
EP 110
DI 10.1007/s12253-016-0100-7
PG 12
ER
PT J
AU Shimizu, A
Kaira, K
Yasuda, M
Asao, T
Ishikawa, O
AF Shimizu, Akira
Kaira, Kyoichi
Yasuda, Masahito
Asao, Takayuki
Ishikawa, Osamu
TI Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK) Expression in Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ER stress; BiP/GRP78; PERK; Prognosis; Malignant melanoma; Skin cancer; Immunohistochemistry
ID ER stress; BiP/GRP78; PERK; Prognosis; Malignant melanoma; Skin cancer; Immunohistochemistry
AB Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin heavy chain binding protein (BiP/GRP78) plays an important role in the endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in various human cancers. The purpose of this study is to examine the prognostic significance of BiP/GRP78 expression in patients with malignant melanoma. A total of 133 malignant melanoma patients were analyzed, and tumor specimens were stained by immunohistochemistry for BiP/ GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34. BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133), respectively. BiP/ GRP78 disclosed a significant relationship with PERK expression, thickness, T factor, N factor, disease staging, cell proliferation (Ki-67) and MVD (CD34). By multivariate analysis, the high expression of BiP/GRP78 was identified as an independent prognostic factor for predicting poor survival against malignant melanoma. The increased BiP/GRP78 expression was clarified as an independent prognostic marker for predicting worse outcome. ER stress marker, BiP/GRP78 could be a powerful molecular target for the treatment of malignant melanoma.
C1 [Shimizu, Akira] Gunma University, Graduate School of Medicine, Department of Dermatology, 3-39-22 Showa-machi, Maebashi, 371-8511 Gunma, Japan.
[Kaira, Kyoichi] Gunma University, Graduate School of Medicine, Department of Oncology Clinical Development, Showa-machi, Maebashi, 371-8511 Gunma, Japan.
[Yasuda, Masahito] Gunma University, Graduate School of Medicine, Department of Dermatology, 3-39-22 Showa-machi, Maebashi, 371-8511 Gunma, Japan.
[Asao, Takayuki] Gunma University, Graduate School of Medicine, Department of Oncology Clinical Development, Showa-machi, Maebashi, 371-8511 Gunma, Japan.
[Ishikawa, Osamu] Gunma University, Graduate School of Medicine, Department of Dermatology, 3-39-22 Showa-machi, Maebashi, 371-8511 Gunma, Japan.
RP Shimizu, A (reprint author), Gunma University, Graduate School of Medicine, Department of Dermatology, 371-8511 Gunma, Japan.
EM shimizuakira@gunma-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 111
EP 116
DI 10.1007/s12253-016-0099-9
PG 6
ER
PT J
AU Romanowicz, H
Pyziak,
Jablonski, F
Brys, M
Forma, E
Smolarz, B
AF Romanowicz, Hanna
Pyziak, Lukasz
Jablonski, Filip
Brys, Magdalena
Forma, Ewa
Smolarz, Beata
TI Analysis of DNA Repair Genes Polymorphisms in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; DNA repair; Genes; Polymorphism
ID Breast cancer; DNA repair; Genes; Polymorphism
AB Genetic polymorphisms in the DNA repair genes may be associated with increased cancer risk. The purpose of this study was to evaluate the association of the DNA repair genes polymorphisms with the risk of breast cancer development. The study included 200 breast cancer patients and 200 healthy controls. The following polymorphisms were studied: C/G (Ser326Cys, rs1052133) of the hOGG1, A/C (IVS5 + 33, rs3212961) of the ERCC1, A/C (Lys939Gln, rs2228001) of the XPC, C/T (Thr241Met, rs861539) of the XRCC3, G/T (Leu787Leu, rs1800392) of the WRN and G/T (Ser307Ser, rs1056503) of the XRCC4 gene. Presented study showed statistically significant increase in the breast cancer development risk of the G/G hOGG1 genotype (OR 8.13; 95 % CI, 4.37– 15.14; p < 0.001) and for the G hOGG1 allele (OR 5.11; 95% CI, 3.69–7.06; p < 0.001), as well as for the C/C ERCC1 genotype (OR 10.61; 95 % CI, 5.72–19.69; p < 0.001) and the C ERCC1 allele (OR 4.66; 95% CI, 3.43–6.34; p < 0.001) in patients with breast cancer in comparison with healthy control group. We also observed positive association of the C/C XPC genotype (OR 3.80; 95 % CI, 2.27–6.38; p < 0.001) as well as the C XPC allele occurrence with an increased breast cancer development risk (OR 2.65; 95 % CI, 1.98–3.55; p < 0.001). Furthermore, we found an association of the G/T WRN gene polymorphism with increased risk of carcinoma. The hOGG1, ERCC1, XPC and WRN genes polymorphisms may be related to development of breast cancer.
C1 [Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Pyziak, Lukasz] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Jablonski, Filip] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Brys, Magdalena] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-237 Lodz, Poland.
[Forma, Ewa] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-237 Lodz, Poland.
[Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
RP Romanowicz, H (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, 93-338 Lodz, Poland.
EM hanna-romanowicz@wp.pl
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 117
EP 123
DI 10.1007/s12253-016-0110-5
PG 7
ER
PT J
AU Oh, RH
An, HCh
Yoo, JN
Lee, HS
AF Oh, Rim Hye
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations in the Mononucleotide Repeats of TAF1 and TAF1L Genes in Gastric and Colorectal Cancers with Regional Heterogeneity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TAF1; TAF1L; Basal transcription component; Mutation; Cancers; Microsatellite instability
ID TAF1; TAF1L; Basal transcription component; Mutation; Cancers; Microsatellite instability
AB Initiation of transcription by RNA polymerase II requires TATA-box-binding protein (TBP)-associated factors (TAFs). TAF1 is a major scaffold by which TBP and TAFs interact in the basal transcription factor. TAF1L is a TAF1 homologue with 95 % amino acid identity with TAF1. TAF1 is involved in apoptosis induction and cell cycle regulation, but roles of TAF1 and TAF1L in tumorigenesis remain unknown. The aim of this study was to explore whether TAF1 and TAF1L genes were mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that TAF1 and TAF1L genes had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI). We analyzed the mutations in 79 GC and 124 CRC by single-strand conformation polymorphism analysis and DNA sequencing. In the present study, we found TAF1 frameshift mutations (3.8 % of CRC with MSI-H) and TAF1L frameshift mutations (2.9 % of GC and 3.8 % of CRC with MSI-H). These mutations were not found in stable MSI/low MSI (MSS/MSI-L) (0/90). In addition, we analyzed intratumoral heterogeneity (ITH) of TAF1 and TAF1L frameshift mutations in 16 CRC and found that two and one CRC harbored regional ITH of TAF1 and TAF1L frameshift mutations, respectively. Our data indicate that TAF1 and TAF1L genes harbored not only somatic mutations but also mutational ITH, which together might play a role in tumorigenesis of GC and CRC with MSI-H. Our results also suggest that ultra-regional mutation analysis is required for a comprehensive evaluation of mutation status in these tumors.
C1 [Oh, Rim Hye] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General Surgery, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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Almendro V, Cheng YK, Randles A, Itzkovitz S, Marusyk A, Ametller E, Gonzalez-Farre X, Munoz M, Russnes HG, Helland A, Rye IH, Borresen-Dale AL, Maruyama R, van Oudenaarden A, DowsettM, Jones RL, Reis-Filho J, Gascon P, GonenM, Michor F, Polyak K, 2014, Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep 6:514–527
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 125
EP 130
DI 10.1007/s12253-016-0107-0
PG 6
ER
PT J
AU Sun, Y
Zhu, L
Chang, X
Chen, J
Lang, J
AF Sun, Yin
Zhu, Lan
Chang, Xiaoyan
Chen, Jie
Lang, Jinghe
TI Clinicopathological Features and Treatment Analysis of Rare Aggressive Angiomyxoma of the Female Pelvis and Perineum – a Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiomyxoma; Diagnosis; Treatment; Prognosis; Genitalia; female; Pelvis
ID Angiomyxoma; Diagnosis; Treatment; Prognosis; Genitalia; female; Pelvis
AB The study was to evaluate the clinicopathological features of aggressive angiomyxoma (AAM) of the female pelvis and perineum and its treatments. This was a retrospective study of female patients with AAM admitted to our hospital. Clinical and pathological data were analyzed, as well as the postsurgical follow-up. Median age at initial presentation was 41 years. Thirteen patients had lesions involving adjacent organs. Eighteen patients underwent complete tumor resection, while one patient underwent partial tumor resection. The tumors were soft in texture, pink in color, and had mucus on the surface. A microscopic examination revealed that the tumors were non-encapsulated, with spindle cells and stellate cells of almost identical size loosely distributed in the myxoid stroma, and vessels of different sizes and wall thicknesses. Immunohistochemistry indicated that AAMs were strongly positive for CD34 and smooth muscle actin, moderately positive for desmin, estrogen receptors and progesterone receptor, and mostly negative for S-100. After a median follow-up of 24 months, the recurrence rate was 33.3 %. Four recurrences were in patients with positive initial margins. AAM is a slow growing, locally invasive, benign tumor. Complete resection could lead to lower recurrence rate compared with incomplete resection. Follow-up is necessary for recurrent cases with repeated surgeries. The overall prognosis could be favorable.
C1 [Sun, Yin] Peking Union Medical College Hospital, Department of Obstetrics and Gynecology, 100000 Beijing, China.
[Zhu, Lan] Peking Union Medical College Hospital, Department of Obstetrics and Gynecology, 100000 Beijing, China.
[Chang, Xiaoyan] Peking Union Medical College Hospital, Department of Pathology, 100000 Beijing, China.
[Chen, Jie] Peking Union Medical College Hospital, Department of Pathology, 100000 Beijing, China.
[Lang, Jinghe] Peking Union Medical College Hospital, Department of Obstetrics and Gynecology, 100000 Beijing, China.
RP Zhu, L (reprint author), Peking Union Medical College Hospital, Department of Obstetrics and Gynecology, 100000 Beijing, China.
EM lanzhusci@126.com
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Siassi RM, Papadopoulos T, Matzel KE, 1999, Metastasizing aggressive angiomyxoma. N Engl J Med 341(23):1772., DOI 10.1056 /NEJM199912023412316
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Blandamura S, Cruz J, Faure Vergara L, Machado Puerto I, Ninfo V, 2003, Aggressive angiomyxoma: a second case of metastasis with patient's death. Hum Pathol 34(10):1072–1074
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 131
EP 137
DI 10.1007/s12253-016-0109-y
PG 7
ER
PT J
AU Kullmann, T
Gauthier, H
Serrate, C
Pouessel, D
le Maignan, Ch
Misset, JL
Culine, S
AF Kullmann, Tamas
Gauthier, Helene
Serrate, Camille
Pouessel, Damien
le Maignan, Christine
Misset, Jean-Louis
Culine, Stephane
TI To Treat or Not to Treat Metastatic Cancer Patients with Poor Performance Status: a Prospective Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastatic cancer; Performance status; Cytotoxic chemotherapy; Supportive care; Therapeutic decision; Survival
ID Metastatic cancer; Performance status; Cytotoxic chemotherapy; Supportive care; Therapeutic decision; Survival
AB Administration of cytotoxic chemotherapy for patients with metastatic cancer and poor performance status is a daily clinical challenge. Guidelines only help to select a therapeutic regimen but do not offer a clear response whether or not the patients should be treated.We performed a prospective analysis in 139 metastatic patients with performance status > 1 according to the Eastern Cooperative Oncology Group scale. A decision was considered correct if patients treated with a medical anticancer treatment lived over 3 months or alternatively patients not treated had a survival under 3 months. The predominant tumor type was non-small cell lung cancer. Patients were chemotherapy naive in 87 cases (63 %). A new line of medical anticancer treatment was started in 107 cases (77 %). The median survival of the study population was 11 weeks (range, 1–53). 84 patients (60 %) died within 3 months while 55 patients (40 %) lived more than 3 months after decision. Treatment decisions were considered as appropriate in 81 cases (58 %). No patient was considered as undertreated. The analysis by pathology allowed to identify pathologies where decisions were correct in the majority of the cases (renal, urothelial and small cell lung cancers), pathologies where appropriate and inappropriate decisions were balanced (prostate, ovarian and breast cancers) and pathologies where decisions for treatment were excessive (non-small cell lung cancer and unknown primary). This prospective study was conducted as part of the evaluation of professional practices in our department. Administration of a medical anticancer treatment validated with patients with good performance status may be harmful for patients with poor performance status. The findings resulted in recommendations for daily practice in order to help physicians, especially for the "don’t go" decisions. Until the identification of new prognostic factors for survival and/or the development of therapies making sensitive currently chemoresistant diseases, the initiation of a medical anticancer treatment outside standard situations should result from a consensual decision team or the inclusion in a clinical trial.
C1 [Kullmann, Tamas] Hopital Saint Louis, Department of Medical OncologyParis, France.
[Gauthier, Helene] Hopital Saint Louis, Department of Medical OncologyParis, France.
[Serrate, Camille] Hopital Saint Louis, Department of Medical OncologyParis, France.
[Pouessel, Damien] Hopital Saint Louis, Department of Medical OncologyParis, France.
[le Maignan, Christine] Hopital Saint Louis, Department of Medical OncologyParis, France.
[Misset, Jean-Louis] Hopital Saint Louis, Department of Medical OncologyParis, France.
[Culine, Stephane] Hopital Saint Louis, Department of Medical OncologyParis, France.
RP Kullmann, T (reprint author), Hopital Saint Louis, Department of Medical Oncology, Paris, France.
EM kullmanndoki@hotmail.com
CR Oken MM, Creech RH, Tormey DC et al, 1982, Toxicity and response criteria of the Eastern Cooperative Oncology group. Am J Clin Oncol 5:649–655
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 139
EP 144
DI 10.1007/s12253-016-0111-4
PG 6
ER
PT J
AU Choi, JE
Kim, SM
Song, YS
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Kim, Sung Min
Song, Yong Sang
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MECOM; Frameshift mutation; Colon cancer; Microsatellite instability; Intratumoral heterogeneity
ID MECOM; Frameshift mutation; Colon cancer; Microsatellite instability; Intratumoral heterogeneity
AB MECOM gene, also known as EVI, encodes a transcriptional regulator involved in hematopoiesis, apoptosis, development and proliferation. In blood system, MECOM is considered an oncogene, but in solid tumors it has both oncogenic and tumor suppressor activities. Low frequent somatic mutations of MECOM have been detected in many cancers including colorectal cancers (CRC), but the mutation status with respect to the microsatellite instability (MSI) has not been studied. There is an A7 mononucleotide repeat in MECOM coding sequences that could be a mutation target in the cancers with MSI. We analyzed the A7 of MECOM in 79 CRCs with high MSI (MSI-H) and 65 microsatellite stable/ low MSI (MSS/MSI-L) CRCs by single-strand conformation polymorphism analysis and DNA sequencing. Overall, we found MECOM frameshift mutations in 6 (7.6 %) CRCs with MSI-H, but not in MSS/MSI-L cancers (0/65) (p<0.025).We also analyzed intratumoral heterogeneity (ITH) of the MECOM frameshift mutation in 16 CRCs and found that four CRCs (25.0 %) harbored regional ITH of the frameshift mutations. Our data indicate that MECOM gene harbors both somatic frameshift mutations and mutational ITH, which together may be features of CRC with MSI-H.
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Weiser R, 2007, The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions. Gene 396:346–357
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Oh HR, An CH, Yoo NJ, Lee SH, 2015, Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in gastric and colorectal cancers. Pathol Oncol Res 21:713–718
Choi MR, An CH, Yoo NJ, Lee SH, 2015, Laminin gene LAMB4 is somatically mutated and expressionally altered in gastric and colorectal cancers. APMIS 123:65–71
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L, 2013, Mutational landscape and significance across 12 major cancer types. Nature 502:333–339
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 145
EP 149
DI 10.1007/s12253-016-0112-3
PG 5
ER
PT J
AU Moldvay, J
Fabian, K
Jackel, M
Nemeth, Zs
Bogos, K
Furak, J
Tiszlavicz, L
Fillinger, J
Dome, B
Schaff, Zs
AF Moldvay, Judit
Fabian, Katalin
Jackel, Marta
Nemeth, Zsuzsanna
Bogos, Krisztina
Furak, Jozsef
Tiszlavicz, Laszlo
Fillinger, Janos
Dome, Balazs
Schaff, Zsuzsa
TI Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Claudin; Immunohistochemistry; Survival
ID Lung cancer; Claudin; Immunohistochemistry; Survival
AB The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0–5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0–1 vs. 2–5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC–ADC and SCC–L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entitywithin the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.
C1 [Moldvay, Judit] National Koranyi Institute of Pulmonology, Piheno u. 1, H-1122 Budapest, Hungary.
[Fabian, Katalin] Semmelweis University, Department of Pulmonology, Diosarok u. 1/c, H-1125 Budapest, Hungary.
[Jackel, Marta] Military Hospital, Department of Pathology, Robert Karoly krt. 44, H-1134 Budapest, Hungary.
[Nemeth, Zsuzsanna] Queen’s University, Centre for Cancer Research and Cell Biology, 97 Lisburn Road, BT9 7AE Belfast, Ireland.
[Bogos, Krisztina] National Koranyi Institute of Pulmonology, Piheno u. 1, H-1122 Budapest, Hungary.
[Furak, Jozsef] University of Szeged, Department of Surgery, Szokefalvi-Nagy u. 6, H-6720 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, Allomas u. 2, H-6720 Szeged, Hungary.
[Fillinger, Janos] National Institute of Oncology, Department of Diagnostic Pathology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Dome, Balazs] National Koranyi Institute of Pulmonology, Piheno u. 1, H-1122 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Moldvay, J (reprint author), National Koranyi Institute of Pulmonology, H-1122 Budapest, Hungary.
EM drmoldvay@hotmail.com
CR Yoshizawa A, Sumiyoshi S, Sonobe M, et al., 2013, Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol 8(1):52–61
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Melchers LJ, Bruine de Bruin L, Schnell U, et al., 2013, Lack of claudin-7 is a strong predictor of regional recurrence in oral and oropharyngeal squamous cell carcinoma. Oral Oncol 49(10):998– 1005
Kim CJ, Lee JW, Choi JJ, et al., 2011, High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma. Eur J Cancer Apr. 47(6):918–925., DOI 10.1016/j.ejca.2010.11.007 Epub 2010 Dec 4
Szasz AM, Nyirady P, Majoros A, et al., 2010, Beta-catenin expression and claudin expression pattern as prognostic factors of prostatic cancer progression. BJU Int 105(5):716–722 Epub 2009 Oct 10
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 151
EP 156
DI 10.1007/s12253-016-0115-0
PG 6
ER
PT J
AU Rekhi, B
Verma, V
Gulia, A
Jambhekar, AN
Desai, S
Juvekar, LSh
Bajpai, J
Puri, A
AF Rekhi, Bharat
Verma, Vivek
Gulia, Ashish
Jambhekar, A Nirmala
Desai, Subhash
Juvekar, L Shashikant
Bajpai, Jyoti
Puri, Ajay
TI Clinicopathological Features of a Series of 27 Cases of Post-Denosumab Treated Giant Cell Tumors of Bones: A Single Institutional Experience at a Tertiary Cancer Referral Centre, India
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Giant cell tumor of bone; Denosumab; Targeted therapy; Bone tumor
ID Giant cell tumor of bone; Denosumab; Targeted therapy; Bone tumor
AB Giant cell tumor of bone (GCTB) is mostly a benign tumor, but associated with recurrences and metastasis. Lately, denosumab is being utilized in the treatment of certain GCTBs. Twenty-seven tumors, analyzed in the present study, occurred in 16 males and 11 females (M: F = 1.45:1), in the age-range of 16 to 47 years (mean = 29.5, median = 29). Most tumors were identified in the tibia(6) and femur(6), followed by the humerus(3), radius(3), pelvis(3), fibula(3), sacrum(1), metacarpal(1) and metatarsal(1) bones. There were 18(66.6 %) primary and 9(33.3 %) recurrent tumors. Exact tumor size (19 cases) varied from 3.7 to 15 cm (mean = 7.8, median = 6.4). Eight of the 19 tumors (42.1 %) had size more than or equal to 8 cm. On histopathologic examination of postdenosumab treated specimens, more than half cases (15)(55.5 %) revealed complete absence of osteoclast-like giant cells (OCLGs) and 12 cases revealed residual OCLGCs. In addition, there was replacement by fibro-osseous tissue, including reactive woven bone or osteoid in most cases, followed by variable amount of spindle cells, hyalinisation, fibrosis and chronic inflammatory cells, including lymphocytes, macrophages and plasma cells. Post-treatment follow-up (25 cases, 92.5 %), over 7–27 months duration (median = 18), revealed 20 cases continuously disease–free. Five patients developed recurrences at 9, 12, 13, 14 and 18 months, respectively. Out of these, who underwent repeat surgical intervention, 4 patients are alive with no evidence of disease and a single patient, planned for a second surgery, is alive-with-disease. Denosumab was mostly offered to patients with large sized, borderline salvageable tumors, in order to decrease the morbidity of index surgical procedure, that led to disappearance of OCLGCs in most cases. Post-denosumab treated GCT cases appear as low grade osteosarcomas on histopathologic examination, but lack the clinical behaviour of an osteosarcoma, therefore may be considered as pseudo malignant bony lesions.
C1 [Rekhi, Bharat] Tata Memorial Hospital, Department of Surgical Pathology, 8th Floor, Annex Building, Dr E.B. Road, Parel, 400012 Mumbai, India.
[Verma, Vivek] Tata Memorial Hospital, Department of Surgical Oncology (Bone and Soft Tissues), Parel, 400012 Mumbai, India.
[Gulia, Ashish] Tata Memorial Hospital, Department of Surgical Oncology (Bone and Soft Tissues), Parel, 400012 Mumbai, India.
[Jambhekar, A Nirmala] Tata Memorial Hospital, Department of Surgical Pathology, 8th Floor, Annex Building, Dr E.B. Road, Parel, 400012 Mumbai, India.
[Desai, Subhash] Tata Memorial Hospital, Department of Radiodiagnosis, Parel, 400012 Mumbai, India.
[Juvekar, L Shashikant] Tata Memorial Hospital, Department of Radiodiagnosis, Parel, 400012 Mumbai, India.
[Bajpai, Jyoti] Tata Memorial Hospital, Department of Medical Oncology, Parel, 400012 Mumbai, India.
[Puri, Ajay] Tata Memorial Hospital, Department of Surgical Oncology (Bone and Soft Tissues), Parel, 400012 Mumbai, India.
RP Rekhi, B (reprint author), Tata Memorial Hospital, Department of Surgical Pathology, 400012 Mumbai, India.
EM rekhi.bharat@gmail.com
CR Athanasou NA, Bansal M, Forsyth R, Reid RP, Sapi Z, 2013, Giant cell tumor of bone. In: Fletcher CD, Bridge JA, Hogendoorn PCW, Mertens F, eds, World Health Organization, WHO, classification of tumors of soft tissue and bone, 4th edn. IARC Press, Lyon pp 321–324
Beebe–Dimmer JL, Cetin K, Fryzek JP, Schuetze SM, Schwartz K, 2009, The epidemiology ofmalignant giant cell tumors of bone: an analysis of data fromthe surveillance, epidemiology and end results program, 1975–2004). Rare Tumors 1:e52
SzendroiM(2004, Giant-cell tumour of bone. J Bone Joint Surg Br 86:5–12
Gupta R, Seethalakshmi V, Jambhekar NA, Prabhudesai S, Merchant N, Puri A, Agarwal M, 2008, Clinicopathologic profile of 470 giant cell tumors of bone from a cancer hospital in western India. Ann Diagn Pathol 12:239–248
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T, 1998, Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597–3602
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Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I, 2013, Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel- group, phase 2 study. Lancet Oncol 14:901–908
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Blay J, Chawla SP, Broto JM, Choy E, Dominkus M, Engellau J, Grimer R, Henshaw RM, Palmerini E, Reichardt P, Rutkowski P, Skubitz KM, Thomas DM, Zhao Y, Qian Y, Jacobs IA, 2011, Denosumab safety and efficacy in giant cell tumor of bone, gctb): interim results from a phase ii study [abstract 10034] J Clin Oncol 29. [Available online at: http://www.asco.org/ASCOv2 /Meetings/Abstracts?&vmview=abst_detail_view&confID=102 &abstractID=82649; cited August 16, 2013]
Aponte-Tinao LA, Piuzzi NS, Roitman P, Farfalli GL, 2015, A high-grade sarcoma arising in a patient with recurrent benign giant cell tumor of the proximal tibia while receiving treatment with denosumab. Clinl Orthopaed Related Res 473:3050–3055
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 157
EP 164
DI 10.1007/s12253-016-0123-0
PG 8
ER
PT J
AU Matrai, Z
Andrikovics, H
Szilvasi, A
Bors, A
Kozma, A
Adam, E
Halm, G
Karaszi,
Tordai, A
Masszi, T
AF Matrai, Zoltan
Andrikovics, Hajnalka
Szilvasi, Aniko
Bors, Andras
Kozma, Andras
Adam, Emma
Halm, Gabriella
Karaszi, Eva
Tordai, Attila
Masszi, Tamas
TI Lipoprotein Lipase as a Prognostic Marker in Chronic Lymphocytic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lipoprotein lipase; CLL; Prognosis; IgVH mutation; 13q deletion; Survival
ID Lipoprotein lipase; CLL; Prognosis; IgVH mutation; 13q deletion; Survival
AB The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism.We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0.0001) and time to first treatment intervals (36 vs 144 months, p < 0.002) were documented. LPL values correlated with male gender, higher stages, more treatment requirement, CD38 positivity and unmutated IgVH genes. Among cases with 13q deletion, LPL positivity identified a subcohort with poor outcome (median survival 108 months vs NR, p < 0.0001). In multivariate analysis, cytogenetic aberrations and LPL had significant impact on survival. Our results confirm that LPL is a strong predictor of outcome in CLL, able to improve prognostic accuracy in good risk cytogenetic subgroups. The relationship between its prognostic and functional role in CLL needs to be explored further.
C1 [Matrai, Zoltan] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Andrikovics, Hajnalka] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Szilvasi, Aniko] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Bors, Andras] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Kozma, Andras] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Adam, Emma] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Halm, Gabriella] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Karaszi, Eva] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Tordai, Attila] National Institute of Haematology, Blood Transfusion and ImmunologyBudapest, Hungary.
[Masszi, Tamas] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Matrai, Z (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Budapest, Hungary.
EM matraiz1@gmail.com
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Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P, Dohner H, Stilgenbauer S, 2002, VH mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 100:1410–1416
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 165
EP 171
DI 10.1007/s12253-016-0132-z
PG 7
ER
PT J
AU Aziz, F
Gao, W
Yan, Q
AF Aziz, Faisal
Gao, Wei
Yan, Qiu
TI Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Correlative biomarkers; Fucosyltransferase IV; Gastritis; Gastric ulcer; Gastric cancer; H. pylori CagA; Lewis Y; P-EGFR
ID Correlative biomarkers; Fucosyltransferase IV; Gastritis; Gastric ulcer; Gastric cancer; H. pylori CagA; Lewis Y; P-EGFR
AB H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n = 128, 176), gastric ulcer (n = 174, 213), and gastric cancer (n = 323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97 %) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p- EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P < 0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R–0.62, −0.74), FUT4 (R–0.81, −0.76) and LeY (R–0.82, −0.70) in gastric tissues and serum (P < 0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.
C1 [Aziz, Faisal] Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Department of Biochemistry and Molecular BiologyDalian, China.
[Gao, Wei] Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Department of Biochemistry and Molecular BiologyDalian, China.
[Yan, Qiu] Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Department of Biochemistry and Molecular BiologyDalian, China.
RP Yan, Q (reprint author), Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Department of Biochemistry and Molecular Biology, Dalian, China.
EM yanqiu63@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 173
EP 179
DI 10.1007/s12253-016-0122-1
PG 7
ER
PT J
AU Ide, M
Koba, Sh
Sueoka-Aragane, N
Sato, A
Nagano, Y
Inoue, T
Misago, N
Narisawa, Y
Kimura, Sh
Sueoka, E
AF Ide, Masaru
Koba, Shinichi
Sueoka-Aragane, Naoko
Sato, Akemi
Nagano, Yuri
Inoue, Takuya
Misago, Noriyuki
Narisawa, Yutaka
Kimura, Shinya
Sueoka, Eisaburo
TI Mutation Profile of B-Raf Gene Analyzed by fully Automated System and Clinical Features in Japanese Melanoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B-raf; Melanoma; Molecular targeted therapy; Tyrosine kinase inhibitors
ID B-raf; Melanoma; Molecular targeted therapy; Tyrosine kinase inhibitors
AB BRAF gene mutations have been observed in 30–50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011. The QP system includes fully automated genotyping, based on analysis of the probe DNA melting curve, which binds the target mutated site using a fluorescent guanine quenched probe. BRAF mutations were detected in 54 of 115 (47 %) including 51 of V600E and 3 of V600 K in Japanese melanoma cases. Among clinical subtypes of melanoma, nodular melanoma showed high frequency (12 of 15; 80 %) of mutation followed by superficial spreading melanoma (13 of 26; 50 %). The QP system is a simple and sensitive method to determine BRAF V600E mutation, and will be useful tool for patient-oriented therapy with BRAF inhibitors.
C1 [Ide, Masaru] Saga University, Faculty of Medicine, Department of Internal MedicineSaga, Japan.
[Koba, Shinichi] Saga University, Faculty of Medicine, Department of DermatologySaga, Japan.
[Sueoka-Aragane, Naoko] Saga University, Faculty of Medicine, Department of Internal MedicineSaga, Japan.
[Sato, Akemi] Saga University, Faculty of Medicine, Department of Internal MedicineSaga, Japan.
[Nagano, Yuri] Saga University, Faculty of Medicine, Department of Internal MedicineSaga, Japan.
[Inoue, Takuya] Saga University, Faculty of Medicine, Department of DermatologySaga, Japan.
[Misago, Noriyuki] Saga University, Faculty of Medicine, Department of DermatologySaga, Japan.
[Narisawa, Yutaka] Saga University, Faculty of Medicine, Department of DermatologySaga, Japan.
[Kimura, Shinya] Saga University, Faculty of Medicine, Department of Internal MedicineSaga, Japan.
[Sueoka, Eisaburo] Saga University, Faculty of Medicine, Department of Clinical Laboratory Medicine, 849-8501 Saga, Japan.
RP Sueoka, E (reprint author), Saga University, Faculty of Medicine, Department of Clinical Laboratory Medicine, 849-8501 Saga, Japan.
EM sueokae@cc.saga-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 181
EP 188
DI 10.1007/s12253-016-0121-2
PG 8
ER
PT J
AU Park, YJ
Yoon, G
AF Park, Y Ji
Yoon, GhilSuk
TI Overexpression of Aquaporin-1 is a Prognostic Factor for Biochemical Recurrence in Prostate Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aquaporin; Prostate adenocarcinoma; Biochemical recurrence; Gleason score
ID Aquaporin; Prostate adenocarcinoma; Biochemical recurrence; Gleason score
AB Aquaporins (AQP) are transmembrane proteins that provide channels for water and solutes, and some are involved in tumor progression and invasion. We evaluated the expression of AQP-1, AQP-3, and AQP-5 and their clinicopathological significance in prostate adenocarcinomas (PCA). Prostatectomy specimens (n = 99) were retrieved from the surgical pathology archives and clinicopathological data were obtained from the medical database at Kyungpook National University Hospital. Immunohistochemical staining for AQP- 1, AQP-3, and AQP-5 was performed on tissue microarrays comprising paired malignant and benign prostatic tissues. Seventeen PCA cases (17.2 %) showed AQP-1 overexpression, specifically 7 tumors (9.7 %) with lower Gleason scores (GS) and 10 tumors (37.0 %) with higher GS, with statistical significance (P = 0.001). AQP-1 overexpression was significantly associated with higher GS (P = 0.001), higher pathologic T (pT) stages (P = 0.024), and biochemical recurrence (BR) (P = 0.002). The difference in AQP-3 and AQP-5 expression between neoplastic and non-neoplastic tissues was not established and there were no correlations with clinicopathological parameters. AQP-1 overexpression was evident in tumors with higher GS, it was less evident in tumors with lower GS, and it was associated with BR and a higher pT stage. AQP-1 overexpression is associated with prostate cancer progression.
C1 [Park, Y Ji] Catholic University of Daegu, School of Medicine, Department of Pathology, Duryugongwon-ro 17-gil, Nam-gu, 42472 Daegu, South Korea.
[Yoon, GhilSuk] Kyungpook National University School of Medicine, Kyungpook National University Medical Center, Department of PathologyDaegu, South Korea.
RP Park, YJ (reprint author), Catholic University of Daegu, School of Medicine, Department of Pathology, 42472 Daegu, South Korea.
EM pathpjy@naver.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 189
EP 196
DI 10.1007/s12253-016-0145-7
PG 8
ER
PT J
AU Shrestha, B
Bajracharya, D
Byatnal, AA
Kamath, A
Radhakrishnan, R
AF Shrestha, Bijayatha
Bajracharya, Dipshikha
Byatnal, Amit Aditi
Kamath, Asha
Radhakrishnan, Raghu
TI May High MMP-2 and TIMP-2 Expressions Increase or Decrease the Aggressivity of Oral Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Invasion; Matrix metalloproteinases; Metastasis; MMP-2; TIMP-2
ID Oral squamous cell carcinoma; Invasion; Matrix metalloproteinases; Metastasis; MMP-2; TIMP-2
AB Matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), may presumably have an important role on the invasion and metastatic spread of malignancies attributed to an uncontrolled degradation of the extracellular matrix (ECM). A retrospective chart analysis was carried out to study the expression of MMP-2 and TIMP-2 on the archival samples of oral squamous cell carcinoma (OSCC) (n = 30) and normal mucosa (n = 10) by immunohistochemistry and compared with the clinicopathologic parameters of cases. Both MMP-2 and TIMP-2 expressions showed a positive correlation with the grades, stages and metastatic capacities of tumors (Spearman’s correlation, p < 0.05). Concomitant increase in the expression of TIMP- 2 and MMP-2 suggested that the rate of MMP-2/TIMP-2 expression is a better marker for characterization of MMP-2 concentration. High expression and/or activity of MMP-2 were linked with poorer survival in OSCC cases, while TIMPs have been shown to apparently act as either growthstimulating or suppressor factors for tumors. It was also revealed that MMP-2 and TIMP-2 were secreted by both tumor cells and stromal cells. A new concept, supposing the dynamic, anticancer partnership between the residual genome stabilizer machinery of tumor cells and defensive cells adjacent to tumors, may illuminate the controversial results. In conclusion, the stronger the infiltrative and metastatic capacity of cancers, the higher is the rate of MMP-2/TIMP-2 expression helping the arrival of humoral and cellular anticancer forces.
C1 [Shrestha, Bijayatha] Chitwan Medical College, Department of Oral PathologyBharatpur, Chitwan, Nepal.
[Bajracharya, Dipshikha] Hospital and Research Center, Kantipur Dental College, Department of Oral PathologyKathmandu, Nepal.
[Byatnal, Amit Aditi] Oral Pathology and MicrobiologyHubli, Karnataka, India.
[Kamath, Asha] Manipal University, Kasturba Medical College, Department of Community MedicineManipal, India.
[Radhakrishnan, Raghu] Manipal University, Manipal College of Dental Sciences, Department of Oral Pathology and Microbiology, 576104 Manipal, India.
RP Radhakrishnan, R (reprint author), Manipal University, Manipal College of Dental Sciences, Department of Oral Pathology and Microbiology, 576104 Manipal, India.
EM raghu.radhakrishnan@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 197
EP 206
DI 10.1007/s12253-016-0149-3
PG 10
ER
PT J
AU Gaal, Zs
Olah,
Rejto, L
Balint, LB
Csernoch, L
AF Gaal, Zsuzsanna
Olah, Eva
Rejto, Laszlo
Balint, Laszlo Balint
Csernoch, Laszlo
TI Expression Levels of Warburg-Effect Related microRNAs Correlate with each Other and that of Histone Deacetylase Enzymes in Adult Hematological Malignancies with Emphasis on Acute Myeloid Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute myeloid leukemia; Warburg-effect; microRNA; oncomiR; Anti-oncomiR; Histone deacetylase
ID Acute myeloid leukemia; Warburg-effect; microRNA; oncomiR; Anti-oncomiR; Histone deacetylase
AB Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR- 125b, while negatively with the level of the tumorsuppressor miR-124. Significant relationships have been confirmed between the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n = 6), the level of miR-125b was significantly lower than in the group of AML patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n = 5), the level of miR-124 was significantly higher compared to the M2 group (n = 7) (p < 0.05). In two cases of FAB M5 AML, the levels of SIRT6 and miR-26a increased during the first 4 weeks of treatment. In the total cohort, white blood cell count at the time of the diagnosis significantly correlated with the levels of HDAC4, SIRT6, miR-124 and miR- 26a. Our results suggest that Warburg-effect related microRNAs may have important role in the pathogenesis of leukemia, and the potential oncogenic property of HDAC4 and SIRT6 cannot be excluded in hematological malignancies. Elevated level of miR-125b can contribute to adverse prognosis of AML without NPM1 mutation. The prevailment of the tumorsuppressor property of miR-124 may depend on the accompanying genetic alterations.
C1 [Gaal, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Olah, Eva] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Rejto, Laszlo] University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Balint, Laszlo Balint] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Csernoch, Laszlo] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
RP Csernoch, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Physiology, H-4012 Debrecen, Hungary.
EM csl@edu.unideb.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 207
EP 216
DI 10.1007/s12253-016-0151-9
PG 10
ER
PT J
AU Liu, P
Zu, X
Liu, L
AF Liu, Peihua
Zu, Xiongbing
Liu, Longfei
TI Genetic Screening in Pheochromocytoma/Paraganglioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Liu, Peihua] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
[Zu, Xiongbing] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
[Liu, Longfei] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
RP Liu, L (reprint author), Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, China.
EM longfei_liu@163.com
CR Patocs A, Lendvai NK, Butz H, Liko I, Sapi Z, Szucs N et al, 2016, Novel SDHB and TMEM127 mutations in patients with pheochromocytoma/Paraganglioma syndrome. Pathol Oncol Res 22(4):673–679
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 217
EP 217
DI 10.1007/s12253-016-0117-y
PG 1
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI USP9X, a Putative Tumor Suppressor Gene, Exhibits Frameshift Mutations in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O’Rourke K, Bazan F, Eastham-Anderson J, Yue P, Dornan D, Huang DC, Dixit VM, 2010, Deubiquitinase USP9X stabilizesMCL1 and promotes tumour cell survival. Nature 463:103–107
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Perez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grutzmann R, Aust D, Rummele P, Knosel T, Herd C, Stemple DL, Kettleborough R, Brosnan JA, Li A, Morgan R, Knight S, Yu J, Stegeman S, Collier LS, ten Hoeve JJ, de Ridder J, Klein AP, Goggins M, Hruban RH, Chang DK, Biankin AV, Grimmond SM, Initiative APCG, Wessels LF, Wood SA, Iacobuzio-Donahue CA, Pilarsky C, Largaespada DA, Adams DJ, Tuveson DA, 2012, The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature 486:266–270
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 219
EP 220
DI 10.1007/s12253-016-0140-z
PG 2
ER
PT J
AU Jo, SY
Song, YS
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Song, Yong Sang
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutations of SMG7 Essential for Nonsense-Mediated mRNA Decay in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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Oh HR, An CH, Yoo NJ, Lee SH, 2015, Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in gastric and colorectal cancers. Pathol Oncol Res 21:713–718
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 221
EP 222
DI 10.1007/s12253-016-0141-y
PG 2
ER
PT J
AU Choi, SK
Kim, T
Yoo, HK
AF Choi, Seung-Kwon
Kim, Taegu
Yoo, Han Koo
TI Spermatocytic Seminoma with Brain Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Choi, Seung-Kwon] Kyung Hee University, School of Medicine, Department of UrologySeoul, South Korea.
[Kim, Taegu] Chung Dam Urologic ClinicNamyangju, South Korea.
[Yoo, Han Koo] Kyung Hee University, School of Medicine, Department of Urology, #149 Sangil-Dong, Gangdong-Gu, 134-727 Seoul, South Korea.
RP Yoo, HK (reprint author), Kyung Hee University, School of Medicine, Department of Urology, 134-727 Seoul, South Korea.
EM malta1@naver.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2017
VL 23
IS 1
BP 223
EP 224
DI 10.1007/s12253-016-0142-x
PG 2
ER
PT J
AU Sabour, L
Sabour, M
Ghorbian, S
AF Sabour, Leila
Sabour, Maryam
Ghorbian, Saeid
TI Clinical Applications of Next-Generation Sequencing in Cancer Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NGS; Cancer; Next-generation sequencing; Diagnosis; Clinical practice
ID NGS; Cancer; Next-generation sequencing; Diagnosis; Clinical practice
AB With the advancement and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research fields. More recently, NGS has been adopted in clinical oncology to advance personalized treatment of cancer. NGS is utilized to novel diagnostic and rare cancer mutations, detection of translocations, inversions, insertions and deletions, detection of copy number variants, detect familial cancer mutation carriers, provide the molecular rationale for appropriate targeted, therapeutic and prognostic. NGS holds many advantages, such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) and the sensitivity, speed in a single test at a relatively low cost compared to be other sequencing modalities. Here we described the technology, methods and applications that can be immediately considered and some of the challenges that lie ahead.
C1 [Sabour, Leila] Islamic Azad University, Ahar Branch, Department of Molecular BiologyAhar, Iran.
[Sabour, Maryam] Islamic Azad University, Ahar Branch, Department of Molecular BiologyAhar, Iran.
[Ghorbian, Saeid] Islamic Azad University, Ahar Branch, Department of Molecular BiologyAhar, Iran.
RP Ghorbian, S (reprint author), Islamic Azad University, Ahar Branch, Department of Molecular Biology, Ahar, Iran.
EM ghorbian20@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 225
EP 234
DI 10.1007/s12253-016-0124-z
PG 10
ER
PT J
AU Nobre, CGC
de Araujo, MGJ
de Medeiros Fernandes, AATh
Cobucci, NOR
Lanza, CFD
Andrade, SV
Fernandes, VJ
AF Nobre, Cristina Guimaraes Camila
de Araujo, Maria Galvao Joselio
de Medeiros Fernandes, Allyrio Araujo Thales
Cobucci, Ney Oliveira Ricardo
Lanza, Carlos Ferreira Daniel
Andrade, Sousa Vania
Fernandes, Verissimo Jose
TI Macrophage Migration Inhibitory Factor (MIF): Biological Activities and Relation with Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Macrophage migration inhibitory factor; Neoplasms; Tumorigenesis; Inflammation
ID Macrophage migration inhibitory factor; Neoplasms; Tumorigenesis; Inflammation
AB Macrophage migration inhibitory factor (MIF) emerged in recent years as an important inflammation mediator, playing a prominent role in the pathogenesis of various types of malignant neoplasm. MIF is a glycoprotein that presents a wide spectrum of biological activities and exerts a complex interaction with various cellular signaling pathways, causing imbalance of homeostasis. Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors. The production of MIF is triggered through an autocrine signal emitted by tumor cells, and stimulates the production of cytokines, chemokines, and growth as well as angiogenic factors that lead to growth of the tumor, increasing its aggressiveness and metastatic potential. MIF is produced by virtually all types of human body cells, in response to stress caused by different factors, leading to pathological conditions such as chronic inflammation and immunomodulation with suppression of immune surveillance and of immune response against tumors, angiogenesis, and carcinogenesis. In this review, we present recent advances on the biological activity of MIF, the signaling pathways with which it is involved and their role in tumorigenesis.
C1 [Nobre, Cristina Guimaraes Camila] Federal University of Rio Grande do Norte, Department of Microbiology and Parasitology, 59072-970 Natal, RN, Brazil.
[de Araujo, Maria Galvao Joselio] Federal University of Rio Grande do Norte, Department of Microbiology and Parasitology, 59072-970 Natal, RN, Brazil.
[de Medeiros Fernandes, Allyrio Araujo Thales] University of Rio Grande do Norte State, Department of Biomedical Sciences, 59607-360 Mossoro, RN, Brazil.
[Cobucci, Ney Oliveira Ricardo] Federal University of Rio Grande do Norte, Department of Microbiology and Parasitology, 59072-970 Natal, RN, Brazil.
[Lanza, Carlos Ferreira Daniel] Federal University of Rio Grande do Norte, CEP, Department of Biochemisty, 59072-970 Natal, RN, Brazil.
[Andrade, Sousa Vania] Federal University of Rio Grande do Norte, Department of Microbiology and Parasitology, 59072-970 Natal, RN, Brazil.
[Fernandes, Verissimo Jose] Federal University of Rio Grande do Norte, Department of Microbiology and Parasitology, 59072-970 Natal, RN, Brazil.
RP de Medeiros Fernandes, AATh (reprint author), University of Rio Grande do Norte State, Department of Biomedical Sciences, 59607-360 Mossoro, Brazil.
EM thalesallyrio@yahoo.com.br
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 235
EP 244
DI 10.1007/s12253-016-0138-6
PG 10
ER
PT J
AU Virag, J
Haberler, Ch
Baksa, G
Piurko, V
Hegedus, Z
Reiniger, L
Balint, K
Chocholous, M
Kiss, A
Lotz, G
Glasz, T
Schaff, Zs
Garami, M
Hegedus, B
AF Virag, Jozsef
Haberler, Christine
Baksa, Gabor
Piurko, Violetta
Hegedus, Zita
Reiniger, Lilla
Balint, Katalin
Chocholous, Monika
Kiss, Andras
Lotz, Gabor
Glasz, Tibor
Schaff, Zsuzsa
Garami, Miklos
Hegedus, Balazs
TI Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ependymoma; Claudin-5; Tight junction; Supratentorial; Choroid plexus epithelium; Prognosis
ID Ependymoma; Claudin-5; Tight junction; Supratentorial; Choroid plexus epithelium; Prognosis
AB Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.
C1 [Virag, Jozsef] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Haberler, Christine] Medical University of Vienna, Department of NeuropathologyVienna, Austria.
[Baksa, Gabor] Semmelweis University, 1st Department of AnatomyBudapest, Hungary.
[Piurko, Violetta] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Hegedus, Zita] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Reiniger, Lilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Balint, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Chocholous, Monika] Medical University of Vienna, Department of PediatricsVienna, Austria.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Glasz, Tibor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Garami, Miklos] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Hegedus, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Hegedus, B (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM balazs.hegedus@meduniwien.ac.at
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 245
EP 252
DI 10.1007/s12253-016-0084-3
PG 8
ER
PT J
AU Rusz, O
Pal, M
Szilagyi,
Rovo, L
Varga, Z
Tomisa, B
Fabian, G
Kovacs, L
Nagy, O
Mozes, P
Reisz, Z
Tiszlavicz, L
Deak, P
Kahan, Zs
AF Rusz, Orsolya
Pal, Margit
Szilagyi, Eva
Rovo, Laszlo
Varga, Zoltan
Tomisa, Bernadett
Fabian, Gabriella
Kovacs, Levente
Nagy, Olga
Mozes, Petra
Reisz, Zita
Tiszlavicz, Laszlo
Deak, Peter
Kahan, Zsuzsanna
TI The Expression of Checkpoint and DNA Repair Genes in Head and Neck Cancer as Possible Predictive Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck cancer; Chemosensitivity; Radiosensitivity; DNA damage response; Gene expression
ID Head and neck cancer; Chemosensitivity; Radiosensitivity; DNA damage response; Gene expression
AB DNA damage response failure may influence the efficacy of DNA-damaging treatments. We determined the expression of 16 genes involved in distinct DNA damage response pathways, in association with the response to standard therapy. Twenty patients with locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric metabolic therapeutic response was determined by [18F]FDG-PET/CT. In the tumor and matched normal tissues collected before treatment, the gene expressions were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). The down-regulation of TP53 was apparently associated with a poor response to iChT, its up-regulation with complete regression in 2 cases. 7 cases with down-regulated REV1 expression showed complete regression after ChRT/RT, while 1 case with REV1 overexpression was resistant to RT. The overexpression of WRN was an independent predictor of tumor relapse. Our results suggest that an altered expression of REV1 predicts sensitivity to RT, while WRN overexpression is an unfavorable prognostic factor.
C1 [Rusz, Orsolya] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Pal, Margit] University of Szeged, Department of Medical Chemistry, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Szilagyi, Eva] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Rovo, Laszlo] Szegedi Tudomanyegyetem, Ful-Orr-Gegeszeti Klinika, Tisza Lajos krt. 111, H-6725 Szeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Tomisa, Bernadett] University of Szeged, Department of Medical Chemistry, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Fabian, Gabriella] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Kovacs, Levente] University of Szeged, Department of Medical Chemistry, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Nagy, Olga] University of Szeged, Department of Medical Chemistry, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Mozes, Petra] Technische Universitat Munchen, Klinikum rechts der Isar, Department of Radiation Oncology, Ismaninger Straße 22, 81675 Munich, Germany.
[Reisz, Zita] University of Szeged, Department of Pathology, Allomas utca 2, H-6720 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, Allomas utca 2, H-6720 Szeged, Hungary.
[Deak, Peter] University of Szeged, Department of Medical Chemistry, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
RP Rusz, O (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM rusz.orsolya@med.u-szeged.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 253
EP 264
DI 10.1007/s12253-016-0088-z
PG 12
ER
PT J
AU Chen, J
Hu, L
Wang, J
Zhang, F
Chen, J
Xu, G
Wang, Y
Pan, Q
AF Chen, Jian
Hu, Lijuan
Wang, Junjun
Zhang, Fan
Chen, Jie
Xu, Gang
Wang, Yumin
Pan, Qinshi
TI Low Expression LncRNA TUBA4B is a Poor Predictor of Prognosis and Regulates Cell Proliferation in Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; lncRNAs; TUBA4B; Prognosis
ID Non-small cell lung cancer; lncRNAs; TUBA4B; Prognosis
AB We aimed to unveil the clinical roles and biological function of lncRNA TUBA4B in on-small cell lung cancer (NSCLC). The relative expression level of TUBA4B was estimated by qPCR in 114 pairs of NSCLC and NT samples and the relation of TUBA4B to clinical data of NSCLC patients was analyzed. We found TUBA4B was lower expressed in NSCLC and five cell lines. The lower expression of TUBA4B was remarkably correlated with advanced TNM stage and lymph node metastasis and served as a predictor for overall survival of NSCLC. After overexpression of TUBA4B, cell proliferation ability of A549 and NCI-H1299 remarkably decreased. Our study ascertained low expression TUBA4B in NSCLC tissue, cell lines and is a poor predictor for prognosis and can regulate cell proliferation in NSCLC.
C1 [Chen, Jian] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Hu, Lijuan] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Wang, Junjun] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Zhang, Fan] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Chen, Jie] The First Affiliated Hospital of Wenzhou Medical University, Department of Intensive Care Unit, 325000 Wenzhou, Zhejiang province, China.
[Xu, Gang] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Wang, Yumin] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
[Pan, Qinshi] The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, Zhejiang province, China.
RP Wang, Y (reprint author), The First Affiliated Hospital of Wenzhou Medical University, Department of Laboratory Medicine, 325000 Wenzhou, China.
EM wym0577@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 265
EP 270
DI 10.1007/s12253-016-0089-y
PG 6
ER
PT J
AU Mahmoudian, AR
Abbaszadegan, RM
Gholamin, M
AF Mahmoudian, Alsadat Reihaneh
Abbaszadegan, Reza Mohammad
Gholamin, Mehran
TI Applying Subtractive Hybridization Technique to Enrich and Amplify Tumor-Specific Transcripts of Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Subtractive hybridization; ESCC; Enrichment; Tumor-specific transcripts; SMART
ID Subtractive hybridization; ESCC; Enrichment; Tumor-specific transcripts; SMART
AB Subtractive hybridization (SH) as an efficient and powerful approach can be applied to isolate differentially expressed transcripts as well as detect of involved mRNAs in various cellular processes, particularly diseases and malignancies. This procedure leads to the enrichment of specific low copy transcripts of tumor cells. Having developed a new approach for SH to isolate tumor specific transcripts, we facilitated discovery of uniquely expressed genes in esophageal squamous cell carcinoma (ESCC). Total RNA was extracted from the fresh tumoral and their adjacent normal tissues, and purified using the Switch Mechanism At the 5ʹ end of Reverse Transcript (SMART) method. Following cDNA synthesis of normal mRNAs using magnetic beads, it was hybridized with tumor mRNAs. To enhance efficiency of subtraction, hybridization was repeated three rounds. Finally, amplification of subtracted tumor-specific transcripts was carried out using in vitro transcription. The subtracted tumoral mRNAs was analyzed quantitatively using real-time PCR for both tumorspecific and housekeeping genes. The subtracted mRNA was confirmed as tumor-specific mRNA pool using RT-PCR and quantitative real-time PCR assessment. The elevated level of tumor-specific transcripts such as MAGE-A4 and CD44 as well as declined copy number of housekeeping genes such as GAPDH, β actin and β2-microglobulin, were confirmed in subtracted tumoral mRNA. The presence of tumor genes was confirmed after the SH procedure. The designed SH method in combination with SMART technique can isolate and amplify high quality tumor-specific transcripts even from small amount of tumor tissues. Removal of common transcripts from the extracted tumoral mRNAs using SH, leads to the enrichment of tumor-specific transcripts. The isolated transcripts are of interest because of their probable roles in ESCC progression and development. In addition, these tumor-specific mRNAs can be applied for future vaccine cancer studies.
C1 [Mahmoudian, Alsadat Reihaneh] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, Bu-Ali Sq, Khorasan Razavi, 9196773117 Mashhad, Iran.
[Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Medical School, Medical Genetics Research CenterMashhad, Iran.
[Gholamin, Mehran] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, Bu-Ali Sq, Khorasan Razavi, 9196773117 Mashhad, Iran.
RP Gholamin, M (reprint author), Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human Genetics, 9196773117 Mashhad, Iran.
EM GholaminM@mums.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 271
EP 279
DI 10.1007/s12253-016-0090-5
PG 9
ER
PT J
AU Gobbo, DA
Fiori, S
Ercoli, G
Bernardo, DA
Parafioriti, A
Fabris, S
Iurlo, A
Neri, A
Bosari, S
Gianelli, U
AF Gobbo, Del Alessandro
Fiori, Stefano
Ercoli, Giulia
Bernardo, Di Andrea
Parafioriti, Antonina
Fabris, Sonia
Iurlo, Alessandra
Neri, Antonino
Bosari, Silvano
Gianelli, Umberto
TI Primary Soft Tissue Lymphomas: Description of Seven Cases and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lymphoma; Soft tissue tumors; FISH; C-myc oncogene
ID Lymphoma; Soft tissue tumors; FISH; C-myc oncogene
AB The present study describes a series of primary soft tissue lymphomas, including immunohistochemical characterization by tissue microarray and cytogenetic profiling. Formalin-fixed, paraffin-embedded tissue samples were collected from patients who underwent soft tissue biopsy. Cases were selected according to the definition of primary soft tissue lymphoma as a lymphoid malignancy arising in soft tissues without evidence of other nodal or extranodal localization for a period of at least 6 months. Our series comprised seven patients with a mean age of 72 years. There were three diffuse large B-cell lymphomas (DLBCLs); one B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma; one DLBCL derived from follicular lymphoma; one ALK-negative anaplastic large cell lymphoma; and one follicular lymphoma. Immunohistochemical and molecular profiles were consistent with the histological diagnoses. The present study contributes to our knowledge about uncommon presentation of lymphoid neoplasms and confirms previously published clinical-pathological data. We present, for the first time, the complete immunohistochemical profile and molecular cytogenetic studies of these lymphoid neoplasms. A rare case of a primary soft tissue ALK-negative anaplastic large cell lymphoma is described in detail.
C1 [Gobbo, Del Alessandro] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, via F. Sforza, 35, 20122 Milan, Italy.
[Fiori, Stefano] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, via F. Sforza, 35, 20122 Milan, Italy.
[Ercoli, Giulia] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, via F. Sforza, 35, 20122 Milan, Italy.
[Bernardo, Di Andrea] Istituto Ortopedico G. Pini, Division of Pathology, p.zza Cardinale A. Ferrari 1, 20122 Milan, Italy.
[Parafioriti, Antonina] Istituto Ortopedico G. Pini, Division of Pathology, p.zza Cardinale A. Ferrari 1, 20122 Milan, Italy.
[Fabris, Sonia] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Hematology Unit, via F. Sforza, 35, 20122 Milan, Italy.
[Iurlo, Alessandra] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Hematology Unit, via F. Sforza, 35, 20122 Milan, Italy.
[Neri, Antonino] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Hematology Unit, via F. Sforza, 35, 20122 Milan, Italy.
[Bosari, Silvano] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, via F. Sforza, 35, 20122 Milan, Italy.
[Gianelli, Umberto] Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, via F. Sforza, 35, 20122 Milan, Italy.
RP Gianelli, U (reprint author), Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Division of Pathology, 20122 Milan, Italy.
EM umberto.gianelli@unimi.it
CR Derenzini E, Casadei B, Pellegrini C, Argnani L, Pileri S, Zinzani PL, 2013, Non-hodgkin lymphomas presenting as soft tissue masses: a single center experience and meta-analysis of the published series. Clin Lymphoma Myeloma Leuk 13:258–265
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Hudacko R, Rapkiewicz A, Berman RS, et al., 2011, ALKnegative anaplastic large cell lymphoma mimicking a soft tissue sarcoma. J Cytol 28:230–233
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Carroll G, BreidahlW, Robbins P, 2013, Musculoskeletal lymphoma: MRI of bone or soft tissue presentations. J Med Imaging Radiat Oncol 57:663–673
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Ishii E, Honda K, Nakagawa A, et al., 2000, Primary CD30/ki- 1 positive anaplastic large cell lymphoma of skeletal muscle with der; 17t(1;17)(q11;p11). Cancer Genet Cytogenet 122:116– 120
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 281
EP 286
DI 10.1007/s12253-016-0096-z
PG 6
ER
PT J
AU Fullar, A
Firneisz, G
Regos, E
Dudas, J
Szarvas, T
Baghy, K
Ramadori, G
Kovalszky, I
AF Fullar, Alexandra
Firneisz, Gabor
Regos, Eszter
Dudas, Jozsef
Szarvas, Tibor
Baghy, Kornelia
Ramadori, Giuliano
Kovalszky, Ilona
TI Response of Hepatic Stellate Cells to TGFB1 Differs from the Response of Myofibroblasts. Decorin Protects against the Action of Growth Factor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatic fibrosis; HSC; Myofibroblast; Decorin; TGF-β signaling
ID Hepatic fibrosis; HSC; Myofibroblast; Decorin; TGF-β signaling
AB Regardless to the exact nature of damage, hepatic stellate cells (HSCs) and other non-parenchymal liver cells transform to activated myofibroblasts, synthesizing the accumulating extracellular matrix (ECM) proteins, and transforming growth factor-β1 (TGF-β1) plays a crucial role in this process. Later it was discovered that decorin, member of the small leucin rich proteoglycan family is able to inhibit this action of TGF-β1. The aim of our present study was to clarify whether HSCs and activated myofibroblasts of portal region exert identical or different response to TGF-β1 exposure, and the inhibitory action of decorin against the growth factor is a generalized phenomenon on myofibroblast of different origin? To this end we measured mRNA expression and production of major collagen components (collagen type I, III and IV) of the liver after stimulation and co-stimulation with TGF-β1 and decorin in primary cell cultures of HSCs and myofibroblasts (MFs). Production of matrix proteins, decorin and members of the TGF-β1 signaling pathways were assessed on Western blots. Messenger RNA expression of collagens and TIEG was quantified by real-time RT-PCR. HSCs and MFs responded differently to TGF-β1 exposure. In contrast to HSCs in which TGF-β1 stimulated the synthesis of collagen type I, type III, and type IV, only the increase of collagen type IV was detected in portal MFs. However, in a combined treatment, decorin seemed to interfere with TGF-β1 and its stimulatory effect was abolished. The different mode of TGF-β1 action is mirrored by the different activation of signaling pathways in activated HSCs and portal fibroblasts. In HSCs the activation of pSMAD2 whereas in myofibroblasts the activation of MAPK pathway was detected. The inhibitory effect of decorin was neither related to the Smad-dependent nor to the Smadindependent signaling pathways.
C1 [Fullar, Alexandra] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Firneisz, Gabor] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Regos, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Dudas, Jozsef] Medical University Innsbruck, Department of OtorhinolaryngologyInnsbruck, Austria.
[Szarvas, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Ramadori, Giuliano] George August University, Department of Gastroenterology and EndocrinologyGottingen, Germany.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM koval@korb1.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 287
EP 294
DI 10.1007/s12253-016-0095-0
PG 8
ER
PT J
AU Varga, N
Mozes, J
Keegan, H
White, Ch
Kelly, Ly
Pilkington, L
Benczik, M
Schaff, Zs
Sobel, G
Koiss, R
Babarczi, E
Nyiri, M
Kovacs, L
Sebe, A
Kaltenecker, B
Geresi, A
Kocsis, A
O’Leary, J
Martin, MC
Jeney, Cs
AF Varga, Norbert
Mozes, Johanna
Keegan, Helen
White, Christine
Kelly, Lynne
Pilkington, Loretto
Benczik, Marta
Schaff, Zsuzsa
Sobel, Gabor
Koiss, Robert
Babarczi, Edit
Nyiri, Miklos
Kovacs, Laura
Sebe, Attila
Kaltenecker, Borbala
Geresi, Adrienn
Kocsis, Adrienn
O’Leary, John
Martin, M Cara
Jeney, Csaba
TI The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV Positive Patients and for Detecting Disease Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; Cervical neoplasia; Case-control study; Cellular biomarker; biomarker; cervical cancer; carcinogenesis
ID Human papillomavirus; Cervical neoplasia; Case-control study; Cellular biomarker; biomarker; cervical cancer; carcinogenesis
AB In the era of primary vaccination against HPV and at the beginning of the low prevalence of cervical lesions, introduction of screening methods that can distinguish between lowand high-grade lesions is necessary in order to maintain the positive predictive value of screening. This case-control study included 562 women who attended cervical screening or were referred for colposcopy and 140 disease free controls, confirmed by histology and/or cytology. The cases were stratified by age. Using routine exfoliated liquid based cytological samples RT-PCR measurements of biomarker genes, high-risk HPV testing and liquid based cytology were performed and used to evaluate different testing protocols including sets of genes/tests with different test cut-offs for the diagnostic panels. Three new panels of cellular biomarkers for improved triage of hrHPV positive women (diagnostic panel) and for prognostic assessment of CIN lesions were proposed. The diagnostic panel (PIK3AP1, TP63 and DSG3) has the potential to distinguish cytologically normal hrHPV+ women from hrHPV+ women with CIN2+. The prognostic gene panels (KRT78, MUC5AC, BPIFB1 and CXCL13, TP63, DSG3) have the ability to differentiate hrHPV+ CIN1 and carcinoma cases. The diagnostic triage panel showed good likelihood ratios for all age groups. The panel showed age-unrelated performance and even better diagnostic value under age 30, a unique feature among the established cervical triage tests. The prognostic gene-panels demonstrated good discriminatory power and oncogenic, antioncogenic grouping of genes. The study highlights the potential for the gene expression panels to be used for diagnostic triage and lesion prognostics in cervical cancer screening.
C1 [Varga, Norbert] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Mozes, Johanna] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Keegan, Helen] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[White, Christine] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[Kelly, Lynne] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[Pilkington, Loretto] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[Benczik, Marta] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, 1091 Budapest, Hungary.
[Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and Gynecology, Ulloi ut 78/a, 1082 Budapest, Hungary.
[Koiss, Robert] Szent Istvan Korhaz, Nogyogyaszati Onkologiai Osztaly, Nagyvarad ter 1, 1087 Budapest, Hungary.
[Babarczi, Edit] Szent Istvan Korhaz, Nogyogyaszati Onkologiai Osztaly, Nagyvarad ter 1, 1087 Budapest, Hungary.
[Nyiri, Miklos] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Kovacs, Laura] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Sebe, Attila] Semmelweis University, Institute of Morphology and Physiology, Nagyvarad ter 4, 1089 Budapest, Hungary.
[Kaltenecker, Borbala] GenoID Molecular Diagnostic Laboratory, Szanatorium u. 19, 1121 Budapest, Hungary.
[Geresi, Adrienn] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[Kocsis, Adrienn] CellCall Ltd, Roppentyu utca 48, 1134 Budapest, Hungary.
[O’Leary, John] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[Martin, M Cara] Trinity College Dublin, School of Medicine, Department of HistopathologyDublin, Ireland.
[Jeney, Csaba] Semmelweis University, Department of Medical Microbiology, Nagyvarad ter 4, 1089 Budapest, Hungary.
RP Jeney, Cs (reprint author), Semmelweis University, Department of Medical Microbiology, 1089 Budapest, Hungary.
EM jencsa@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 295
EP 305
DI 10.1007/s12253-016-0094-1
PG 11
ER
PT J
AU He, J
Tan, W
Tang, X
Ma, J
AF He, Jinfeng
Tan, Wei
Tang, Xuelian
Ma, Jingping
TI Variations in EGFR ctDNA Correlates to the Clinical Efficacy of Afatinib in Non Small Cell Lung Cancer with Acquired Resistance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non small cell lung cancer (NSCLC); EGFR mutations; Acquired resistance; Afatinib; ctDNA
ID Non small cell lung cancer (NSCLC); EGFR mutations; Acquired resistance; Afatinib; ctDNA
AB Monitoring of non small cell lung cancer (NSCLC) patients on afatinib after acquired resistance to 1st generation tyrosine kinase inhibitors is important. Circulating tumor DNA (ctDNA) offers an attractive means other than conventional tissue biopsy to characterize real time dynamic changes of the disease. In our study, we aim to ascertain the clinical value for ctDNA monitoring of NSCLC patientswith acquired resistance for afatinib treatment. 200 patients positive for the activating epithermal growth factor receptor (EGFR) mutations were recruited for the study. Baseline molecular profiling for L858R, Exon 19 deletion and T790M were performed. Thereafter, serial blood samples were taken and patients were assessed by overall survival (OS) to determine the usefulness of ctDNA monitoring. At baseline, matched tumor biopsy and ctDNA analysis had a concordance agreement of 93.5% for L858R and exon 19 deletion. We also determined that a large proportion of patients had the drug resistance mutation T790Mprior to starting afatinib and these patients were linked to a worse survival outcome. For patients that registered a drop in ctDNA levels after afatinib was administered, we observed that their survival outcome was more favorable (hazard ratio 1.56, (95% CI 1.04 to 2.43). ctDNA levels were mostly elevated after the 3rd sampling cycle. Our results suggest that ctDNA can be used to predict the clinical benefits of afatinib treatment. Pre and post blood sampling aids to identify patient groups that may benefit most from the treatment and ctDNA is relatively sensitive to address the dynamic changes of the disease at the molecular level.
C1 [He, Jinfeng] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Respiratory Medicine, Renmin Road 1, 434020 Jingzhou, China.
[Tan, Wei] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Haemodialysis CentreJingzhou, China.
[Tang, Xuelian] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Respiratory Medicine, Renmin Road 1, 434020 Jingzhou, China.
[Ma, Jingping] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Respiratory Medicine, Renmin Road 1, 434020 Jingzhou, China.
RP Ma, J (reprint author), Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Respiratory Medicine, 434020 Jingzhou, China.
EM mjpjzhospital@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 307
EP 315
DI 10.1007/s12253-016-0097-y
PG 9
ER
PT J
AU Lutkowska, A
Roszak, A
Jagodzinski, PP
AF Lutkowska, Anna
Roszak, Andrzej
Jagodzinski, P Pawel
TI 17β-hydroxysteroid dehydrogenase type Gene 1937 A > G Polymorphism as a Risk Factor for Cervical Cancer Progression in the Polish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical carcinoma; HSD17B1; Polymorphisms
ID Cervical carcinoma; HSD17B1; Polymorphisms
AB The role of 17β-estradiol (E2) in the development of cervical tumor (CT) has been demonstrated. 17β Hydroxysteroid dehydrogenase type 1 (HSD17B1) converts estrone (E1) into E2.We aimed to study the distribution of the HSD17B1937 A > G (rs605059) single nucleotide polymorphism (SNP) in women (n = 383) with CT and controls (n = 401) from the Polish population. The p-trend value evaluated for HSD17B1 rs605059 was 0.0233 for all patients. The A/A vs G/G genotype significantly contributed to all patients with CT, and the Odds Ratio (OR) was 1.570 (95 % CI = 1.053–2.343; p = 0.0266). Stratification of the patients based on tumor stage and histological grade indicated the contribution of HSD17B1937 A > G to stages III and IV. The p-value was 0.0010. The OR for the A/Avs G/G genotype was 2.992 (95 % CI = 1.627–5.502, p = 0.0003), the OR for the A/G vs G/G genotype was 2.545 (95 % CI = 1.410–4.593, p = 0.0015) and the OR for the A/A and A/G vs G/G genotype was 2.724 (95 % CI = 1.546–4.799, p = 0.0004). Moreover, we observed a contribution of the rs605059 SNP to histological grade G3 status. The p-value was 0.0042. The OR for the A/A vs G/G genotype was 5.632 (95 % CI = 1.644–19.290, p = 0.0026), the OR for the A/G vs G/G genotype was 4.213 (95%CI = 1.244–14.265, p = 0.0113) and the OR for the A/A and A/G vs G/G genotype was 4.780 (95 % CI = 1.456– 15.687, p = 0.0033). Our study indicated that the HSD17B1937 A > G transition is a risk factor for CT, especially for stages III and IV and histological grade G3.
C1 [Lutkowska, Anna] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
[Roszak, Andrzej] Greater Poland Cancer Center, Department of Radiotherapy and Gynecological OncologyPoznan, Poland.
[Jagodzinski, P Pawel] Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St, 60-781 Poznan, Poland.
RP Jagodzinski, PP (reprint author), Poznan University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznan, Poland.
EM pjagodzi@am.poznan.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 317
EP 322
DI 10.1007/s12253-016-0103-4
PG 6
ER
PT J
AU Tan, Ch
Qian, X
Ge, Y
Yang, B
Wang, F
Guan, Z
Cai, J
AF Tan, Cheng
Qian, Xia
Ge, Yangyang
Yang, Baixia
Wang, Feng
Guan, Zhifeng
Cai, Jing
TI Oroxylin a could be a Promising Radiosensitizer for Esophageal Squamous Cell Carcinoma by Inducing G2/M Arrest and Activating Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OroxylinA; Radiosensitization; ESCC; Apoptosis; G2/M arrest
ID OroxylinA; Radiosensitization; ESCC; Apoptosis; G2/M arrest
AB To evaluate the radiosensitization of Oroxylin A on esophageal carcinoma cell as well as the optimal scheduling of Oroxylin A and radiotherapy (RT). Cell proliferation was estimated by aCCK8 assay.Radiosensitizationwas evaluated by a clonogenic survival assay. The progressions of Cell apoptosis and Cell cycle were investigated by flow cytometry. Expressions of survivin and cell cycle regulators were evaluated by Western blot analysis. A dose-dependent cell survival reduction was found in response to radiation with or without Oroxylin A. The apoptosis rates were remarkably dosedependent higher in combination groups than in either Oroxylin A or radiation alone group. Besides, Oroxylin A could obviously radiosensitize ESCC cells by arresting tumor cells in G2/M phase and regulating cyclin B1 and Cdc 2 protein expression. Oroxylin A could be a promising radiosensitizer for esophageal squamous cell carcinoma by inducing G2/M phase blocking and activating cell apoptosis.
C1 [Tan, Cheng] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Qian, Xia] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Ge, Yangyang] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Yang, Baixia] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Wang, Feng] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Guan, Zhifeng] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
[Cai, Jing] Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
RP Cai, J (reprint author), Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Department of Radiation Oncology, 226321 Nantong, China.
EM cj7227@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 323
EP 328
DI 10.1007/s12253-016-0106-1
PG 6
ER
PT J
AU Zhang, Z
He, Q
Fu, S
Zheng, Z
AF Zhang, Zhe
He, Qinsi
Fu, Si
Zheng, Zhi
TI Estrogen Receptors in Regulating Cell Proliferation of Esophageal Squamous Cell Carcinoma: Involvement of Intracellular Ca2+ Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Estrogen receptor; Esophageal squamous cell carcinoma; Gender difference; Cell proliferation; Ca2+ signaling
ID Estrogen receptor; Esophageal squamous cell carcinoma; Gender difference; Cell proliferation; Ca2+ signaling
AB Esophageal cancer is a deadly disease in the esophagus with a poor prognosis. Over 90 % of esophageal cancer is esophageal squamous cell carcinoma (ESCC) and its pathogenic mechanisms remain unclear. Epidemiology study found a strong gender difference with a sex ratio of 8–9:1 in favor of males, but the molecular mechanisms for so striking gender difference are poorly understood so far. In the present study, we demonstrated the expression of estrogen receptors in human ESCC cells. 17β-E2 but not 17α-E2 was found to dosedependently suppress the cell proliferation of human ESCC cells, which was attenuated by estrogen receptor antagonist ICI1 82,780. Furthermore, 17β -E2 but not 17α-E2 10 nM markedly induced both intracellular Ca2+ release and extracellular Ca2+ entry into ESCC cells, which was again attenuated by estrogen receptor antagonist ICI182,780. Taken together, our data clearly demonstrate that estrogen exerts anti-proliferative action on human ESCC cells likely through estrogen receptor-Ca2+ signaling pathway, which may provide a reasonable explanation on the striking male predominance of ESCC.
C1 [Zhang, Zhe] China-Japan Friendship Hospital, Department of Chinese Medical Gastrointestinal, 2 Yinghua Dongjie, 100029 Beijing, Beijing, China.
[He, Qinsi] Nanchang University, 330029 Nanchang, Jiangxi, China.
[Fu, Si] China-Japan Friendship Hospital, Department of Chinese Medical Gastrointestinal, 2 Yinghua Dongjie, 100029 Beijing, Beijing, China.
[Zheng, Zhi] Nanchang University, 330029 Nanchang, Jiangxi, China.
RP Zheng, Z (reprint author), Nanchang University, 330029 Nanchang, China.
EM zheng_sheva@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 329
EP 334
DI 10.1007/s12253-016-0105-2
PG 6
ER
PT J
AU Ljujic, M
Mijatovic, S
Bulatovic, ZM
Mojic, M
Maksimovic-Ivanic, D
Radojkovic, D
Topic, A
AF Ljujic, Mila
Mijatovic, Sanja
Bulatovic, Z Mirna
Mojic, Marija
Maksimovic-Ivanic, Danijela
Radojkovic, Dragica
Topic, Aleksandra
TI Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Alpha-1-antitrypsin; Cisplatin; Prostate cancer; Melanoma cancer
ID Alpha-1-antitrypsin; Cisplatin; Prostate cancer; Melanoma cancer
AB Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear.We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NFkB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.
C1 [Ljujic, Mila] University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11221 Belgrade, Serbia.
[Mijatovic, Sanja] University of Belgrade, Institute for Biological Research, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
[Bulatovic, Z Mirna] University of Belgrade, Institute for Biological Research, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
[Mojic, Marija] University of Belgrade, Institute for Biological Research, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
[Maksimovic-Ivanic, Danijela] University of Belgrade, Institute for Biological Research, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
[Radojkovic, Dragica] University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11221 Belgrade, Serbia.
[Topic, Aleksandra] Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, Vojvode Stepe 450, 11221 Belgrade, Serbia.
RP Topic, A (reprint author), Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, 11221 Belgrade, Serbia.
EM aleksandra.topic1@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 335
EP 343
DI 10.1007/s12253-016-0104-3
PG 9
ER
PT J
AU Zepeda-Nuno, SJ
Guerrero-Velazquez, C
Del Toro-Arreola, S
Vega-Magana, N
Angeles-Sanchez, J
Haramati, J
Pereira-Suarez, LA
Bueno-Topete, RM
AF Zepeda-Nuno, Sergio Jose
Guerrero-Velazquez, Celia
Del Toro-Arreola, Susana
Vega-Magana, Natali
Angeles-Sanchez, Julian
Haramati, Jesse
Pereira-Suarez, L Ana
Bueno-Topete, R Miriam
TI Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral cancer; ADAM10; sFasL; Fas; FasL
ID Oral cancer; ADAM10; sFasL; Fas; FasL
AB ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2),ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (IIIIV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.
C1 [Zepeda-Nuno, Sergio Jose] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de Microbiologia y Patologia, Laboratorio de PatologiaGuadalajara, Jalisco, Mexico.
[Guerrero-Velazquez, Celia] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Instituto de Investigacion en Odontologia, Departamento de Clinicas Odontologicas IntegralesGuadalajara, Jalisco, Mexico.
[Del Toro-Arreola, Susana] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco, Mexico.
[Vega-Magana, Natali] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco, Mexico.
[Angeles-Sanchez, Julian] Instituto Jalisciense de Cancerologia, Clinica de Tumores de Cabeza y CuelloGuadalajara, Jalisco, Mexico.
[Haramati, Jesse] Centro Universitario de Ciencias Biologicas y Agropecuarias, Universidad de Guadalajara, Departamento de Biologia Celular y Molecular, Laboratorio de InmunologiaGuadalajara, Jalisco, Mexico.
[Pereira-Suarez, L Ana] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de Fisiologia, Laboratorio de InmunologiaGuadalajara, Jalisco, Mexico.
[Bueno-Topete, R Miriam] Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco, Mexico.
RP Bueno-Topete, RM (reprint author), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, 44340 Guadalajara, Mexico.
EM ruthmyriamtop@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 345
EP 353
DI 10.1007/s12253-016-0102-5
PG 9
ER
PT J
AU Moazeni-Roodi, A
Allameh, A
Harirchi, I
Motiee-Langroudi, M
Garajei, A
AF Moazeni-Roodi, Abdolkarim
Allameh, Abdolamir
Harirchi, Iraj
Motiee-Langroudi, Maziar
Garajei, Ata
TI Studies on the Contribution of Cox-2 Expression in the Progression of Oral Squamous Cell Carcinoma and H-Ras Activation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OSCC; Oncogene; H-ras; Cox-2; Smoking; Iran
ID OSCC; Oncogene; H-ras; Cox-2; Smoking; Iran
AB The aim of this study was to investigate the relationship between the H-ras and Cox-2 gene expression in tumors from Iranian Oral Squamous Cell Carcinoma (OSCC) patients. Fresh tumor biopsies removed from oral cavity were collected from 67 new cases. Total RNA was extracted from biopsies and processed for quantification of H-ras and Cox-2 specific RNA expression using real-time PCR (QPCR). In addition, 59 gingival biopsies from apparently normal individuals were processed for QPCR assays. The results showed that Cox-2 expression at mRNA levels was at minimal levels in normal gingival biopsies. However, there was a surge in Cox-2 expression in tumor tissues (11.5 fold, p < 0.0001). Cox-2 expression was elevated depending on the tumor grade and there was a 1.7 fold increase (p = 0.003) in tumors diagnosed as MD/PD compared to that pathologically diagnosed as WD. This inflammatory marker was increased more significantly in smoker patients compared to non-smoker matching group. The H-ras expression at mRNA levels was significantly higher in OSCC samples compared to normal gingival (3 fold; p = 0.044). This expression was significantly higher in tumors diagnosed as MD/PD compared to WD(1.59 fold, p = 0.033). In conclusion, we found a correlation between H-ras expression and Cox-2 induction in OSCC tissue, suggesting that together these genes are contributing to cancer progression. Cox-2 is an early event in cancers of mucosal epithelial cells and a surge in Cox-2 expression in OSCC could be partly due to proinflammatory factors such as smoking.
C1 [Moazeni-Roodi, Abdolkarim] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, I.R., Iran.
[Allameh, Abdolamir] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, I.R., Iran.
[Harirchi, Iraj] Tehran University of Medical Sciences, Cancer Institute of IranTehran, I.R., Iran.
[Motiee-Langroudi, Maziar] Tehran University of Medical Sciences, Cancer Institute of IranTehran, I.R., Iran.
[Garajei, Ata] Tehran University of Medical Sciences, Department of Head and Neck Surgical Oncology and Reconstructive Surgery, School of Medicine, Department of Oral and Maxillofacial Surgery, School of DentistryTehran, Iran.
RP Allameh, A (reprint author), Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical Biochemistry, Tehran, Iran.
EM allameha@modares.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 355
EP 360
DI 10.1007/s12253-016-0114-1
PG 6
ER
PT J
AU Liu, P
Jiang, W
Zhou, Sh
Gao, J
Zhang, H
AF Liu, Pengfei
Jiang, Wenhua
Zhou, Shiyong
Gao, Jun
Zhang, Huilai
TI Combined Analysis of ChIP Sequencing and Gene Expression Dataset in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Chromatin Immunoprecipitation combined with high-throughput sequencing (ChIP-seq); Human protein reference database (HPRD); Protein-protein interaction (PPI)
ID Breast cancer; Chromatin Immunoprecipitation combined with high-throughput sequencing (ChIP-seq); Human protein reference database (HPRD); Protein-protein interaction (PPI)
AB Breast cancer is a common malignancy in women and contribute largely to the cancer related death. The purpose of this study is to confirm the roles of GATA3 and identify potential biomarkers of breast cancer. Chromatin Immunoprecipitation combined with high-throughput sequencing (ChIP-Seq) (GSM1642515) and gene expression profiles (GSE24249) were downloaded from the Gene Expression Omnibus (GEO) database. Bowtie2 and MACS2 were used for the mapping and peak calling of the ChIP-Seq data respectively. ChIPseeker, a R bioconductor package was adopted for the annotation of the enriched peaks. For the gene expression profiles, we used affy and limma package to do normalization and differential expression analysis. The genes with fold change >2 and adjusted P-Value <0.05 were screened out. Besides, BETA (Binding and Expression Target Analysis) was used to do the combined analysis of ChIP-Seq and gene expression profiles. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for the functional enrichment analysis of overlapping genes between the target genes and differential expression genes (DEGs). What’s more, the protein-protein interaction (PPI) network of the overlapping genes was obtained through the Human Protein Reference Database (HPRD). A total of 46,487 peaks were identified for GATA3 and out of which, 3256 ones were found to located at −3000 ~ 0 bp from the transcription start sites (TSS) of their nearby gene. A total of 236 down- and 343 up-regulated genes were screened out in GATA3 overexpression breast cancer samples compared with those in control. The combined analysis of ChIP-Seq and gene expression dataset showed GATA3 act as a repressor in breast cancer. Besides, 68 overlaps were obtained between the DEGs and genes included in peaks located at −3000 ~ 0 bp from TSS. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cancer progression and gene regulation were found to be enriched in those overlaps. In the PPI network, NDRG1, JUP and etc. were found to directly interact with large number of genes, which might indicate their important roles in the progression of breast cancer.
C1 [Liu, Pengfei] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, 300060 Tianjin, China.
[Jiang, Wenhua] The Second Hospital of Tianjin Medical University, Department of Radiotherapy, 300211 Tianjin, China.
[Zhou, Shiyong] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, 300060 Tianjin, China.
[Gao, Jun] Hengshui Harrison International Peace Hospital, Department of Oncology, 053000 Hebei, China.
[Zhang, Huilai] National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, 300060 Tianjin, China.
RP Zhang, H (reprint author), National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, 300060 Tianjin, China.
EM snowlpf@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 361
EP 368
DI 10.1007/s12253-016-0116-z
PG 8
ER
PT J
AU Peng, G
Liao, Y
Shen, Ch
AF Peng, Gang
Liao, Yiwei
Shen, Chenfu
TI miRNA-429 Inhibits Astrocytoma Proliferation and Invasion by Targeting BMI1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; miRNA-429; BMI1; Proliferation; Invasion
ID Glioblastoma; miRNA-429; BMI1; Proliferation; Invasion
AB Glioblastoma multiforme (GBM), the most common primary brain cancer in adults, is usually the most lethal type of brain tumor. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that deeply involves with the regulation of gene expression and cellular processes, including proliferation, apoptosis, migration and invasion. The objective of the study is to investigate the effect of miRNA- 429 on human glioblastoma tissues and cell lines. miRNA- 429 expressions in human glioblastoma, normal brain tissue samples, and human malignant glioma cell lines (U87, U251 and LN229) were compared using reverse transcriptionquantitative PCR and western blot methods. U251 cell lines were transfected with miRNA-429 mimics, and then the effects of miRNA-429 on cell proliferation and invasion were investigated by CCK8 and Transwell invasion assay, respectively. It was found that miRNA-429 expression was significantly reduced in the examined Glioblastoma samples and human glioma cell lines. Overexpression of miRNA-429 inhibited Glioblastoma cell proliferation and invasion. Additionally, the present study also showed that BMI1 was a functional target of miRNA-429. Overexpression of BMI1 undermined the inhibition effect of miRNA-429 in glioblastoma and U251 cell lines. The current study demonstrated that miRNA-429, as a tumor suppressor gene, was capable of negatively regulating the expression of BMI1 in U251 cells.
C1 [Peng, Gang] Central South University, Xiangya Hospital, Department of Neurosurgery, 87 XiangYa Road, 410008 Changsha, Hunan Province, China.
[Liao, Yiwei] Central South University, Xiangya Hospital, Department of Neurosurgery, 87 XiangYa Road, 410008 Changsha, Hunan Province, China.
[Shen, Chenfu] Central South University, Xiangya Hospital, Department of Neurosurgery, 87 XiangYa Road, 410008 Changsha, Hunan Province, China.
RP Shen, Ch (reprint author), Central South University, Xiangya Hospital, Department of Neurosurgery, 410008 Changsha, China.
EM shenchenfu@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 369
EP 376
DI 10.1007/s12253-016-0113-2
PG 8
ER
PT J
AU Madaras, B
Horvath, Zs
Graf, L
Galffy, G
Tamasi, L
Ostoros, Gy
Dome, B
Morocz,
Bartfai, Z
Prohaszka, Z
Kocsis, J
AF Madaras, Balazs
Horvath, Zsolt
Graf, Laszlo
Galffy, Gabriella
Tamasi, Lilla
Ostoros, Gyula
Dome, Balazs
Morocz, Eva
Bartfai, Zoltan
Prohaszka, Zoltan
Kocsis, Judit
TI Serum Heat Shock Protein 70, as a Potential Biomarker for Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Small cell lung cancer; Hsp70; Biomarker; Prognostic marker; Target
ID Small cell lung cancer; Hsp70; Biomarker; Prognostic marker; Target
AB The 70 kDa heat shock protein (Hsp70) is a highly conservative molecular chaperone, that has important role in cell integrity. Recently considerable amount of data are accumulating on the potential role of Hsp70 in carcinogenesis and tumor progression. Most papers are focusing on intracellular or membrane bound protein, however very limited data exist on serum Hsp70, that can also induce innate and adaptive immune response. Previously we have published data on the correlation between coloretal cancer progression and serum Hsp70 concentration. The objective of this study was to compare the serum Hsp70 level in patients with small cell lung cancer (SCLC n = 70) and age matched healthy controlls (n = 121) and correlate Hsp70 level with other known serum biomarkers (LDH and NSE) of the disease.We found that the serum level of Hsp70 was significantly higher in SCLC patients compared to control subjects (mean value 6.91 vs 2.47 ng/ml, p = 0.001). The highest Hsp70 concentration was measured in stage IV advanced SCLC (Stage IV versus Stage I-III disease: 9.91 vs 4.38 ng/ml, p = 0.003). The serum Hsp70 level correlated with serum LDH (r = 0.426, p < 0,001) and NSE level (r = 0.455, p < 0,001). We found that high serum Hsp70 level predicted unfavorable survival, risk of death within 1 year was more than 3 times higher in patients with high baseline Hsp70 level (HR:3.509, CI: 1.066–11.562; p = 0.039). Our observations indicate that serum Hsp70 could be a valuable diagnostic and prognostic marker in small cell lung cancer.
C1 [Madaras, Balazs] National Institute of OncologyBudapest, Hungary.
[Horvath, Zsolt] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Graf, Laszlo] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Galffy, Gabriella] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Ostoros, Gyula] National Koranyi Institute of Pulmonology, Department of Tumor BiologyBudapest, Hungary.
[Dome, Balazs] National Koranyi Institute of Pulmonology, Department of Tumor BiologyBudapest, Hungary.
[Morocz, Eva] County Hospital of PulmonologyTorokbalint, Hungary.
[Bartfai, Zoltan] Soproni Erzsebet Oktato Korhaz es Rehabilitacios IntezetSopron, Hungary.
[Prohaszka, Zoltan] Semmelweis University, 3rd Department of Internal MedicineBudapest, Hungary.
[Kocsis, Judit] University of Debrecen, Department of OncologyDebrecen, Hungary.
RP Kocsis, J (reprint author), University of Debrecen, Department of Oncology, Debrecen, Hungary.
EM kocsis.judit@med.unideb.hu;kocsisjucidr@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 377
EP 383
DI 10.1007/s12253-016-0118-x
PG 7
ER
PT J
AU Zidi, S
Stayoussef, M
Alsaleh, LB
Gazouani, E
Mezlini, A
Ebrahim, HB
Yacoubi-Loueslati, B
Almawi, YW
AF Zidi, Sabrina
Stayoussef, Mouna
Alsaleh, L Bano
Gazouani, Ezzedine
Mezlini, Amel
Ebrahim, H Bashayer
Yacoubi-Loueslati, Besma
Almawi, Y Wassim
TI Relationships between Common and Novel Interleukin-6 Gene Polymorphisms and Risk of Cervical Cancer: a Case-Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Interleukin-6; Cervical cancer; FIGO stages; Polymorphisms; Haplotypes; Tunisians
ID Interleukin-6; Cervical cancer; FIGO stages; Polymorphisms; Haplotypes; Tunisians
AB We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P = 0.033; OR =0.49(0.25–0.95)) and major allele (P = 0.037; OR = 0.57 (0.33–0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P = 0.014; OR = 0.53(0.32– 0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P = 0.044; OR = 0.39 (0.15–1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P = 0.047; OR = 1.97 (0.94–4.13)) and smoking (P < 0.001; OR = 7.12 (2.97–17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Stayoussef, Mouna] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Alsaleh, L Bano] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
[Gazouani, Ezzedine] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Ebrahim, H Bashayer] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
[Yacoubi-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Almawi, Y Wassim] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 385
EP 392
DI 10.1007/s12253-016-0127-9
PG 8
ER
PT J
AU Ersen, A
Pekmezci, M
Folpe, LA
Tihan, T
AF Ersen, Ayca
Pekmezci, Melike
Folpe, L Andrew
Tihan, Tarik
TI Comparision of New Diagnostic Tools for Malignant Peripheral Nerve Sheath Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Malignant peripheral nerve sheath tumor; SOX10; SOX2; p75NTR; H3K27
ID Malignant peripheral nerve sheath tumor; SOX10; SOX2; p75NTR; H3K27
C1 [Ersen, Ayca] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Pekmezci, Melike] University of California San Francisco, Department of Pathology, Division of Neuropathology, 94143 San Francisco, CA, USA.
[Folpe, L Andrew] Mayo Clinic, Anatomic Pathology DivisionRochester, MN, USA.
[Tihan, Tarik] University of California San Francisco, Department of Pathology, Division of Neuropathology, 94143 San Francisco, CA, USA.
RP Ersen, A (reprint author), Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Izmir, Turkey.
EM ayca.ersen@deu.edu.tr
CR Louis DN, Ohgaki H, Wiestler OD, 2016, Cavenee WKe. World Health Organization histological classification of Tumours of the central nervous system. Lyon, France, International Agency for Research on Cancer
Rodriguez FJ, Folpe AL, Giannini C, Perry A, 2012, Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 123:295–319
Thway K, Hamarneh W, Miah AB, Fisher C, 2015, Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous and glandular elements: rare epithelial differentiation in a triton tumor. Int J Surg Pathol 23:377–383
Louis DN, Ohgaki H, Wiestler OD, Cavenee WKe, 2016, World Health Organization histological classification of tumours of the central nervous system, Revised 4th Edition). In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds). International Agency for Research on Cancer, Lyon, France
Kang Y, Pekmezci M, Folpe AL et al, 2014, Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma. Mod Pathol 27:55–61
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 393
EP 398
DI 10.1007/s12253-016-0125-y
PG 6
ER
PT J
AU Huang, KCh
Evans, A
Donnelly, B
Bismar, AT
AF Huang, Kuo-Cheng
Evans, Andrew
Donnelly, Bryan
Bismar, A Tarek
TI SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ERG; PTEN deletion; Homozygous; Hemizygous; SPINK1; Prostate cancer; Progression; Biomarkers
ID ERG; PTEN deletion; Homozygous; Hemizygous; SPINK1; Prostate cancer; Progression; Biomarkers
AB SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6%of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1’s association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence postradical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.
C1 [Huang, Kuo-Cheng] University of Calgary and Calgary Laboratory Services, Department of Pathology and Laboratory Medicine, 7007, 14sth st sw, T2V 1P9 Calgary, AB, Canada.
[Evans, Andrew] University Health Network and University of Toronto, Department of PathologyToronto, ON, Canada.
[Donnelly, Bryan] University of Calgary, Department of UrologyCalgary, AB, Canada.
[Bismar, A Tarek] University of Calgary and Calgary Laboratory Services, Department of Pathology and Laboratory Medicine, 7007, 14sth st sw, T2V 1P9 Calgary, AB, Canada.
RP Bismar, AT (reprint author), University of Calgary and Calgary Laboratory Services, Department of Pathology and Laboratory Medicine, T2V 1P9 Calgary, Canada.
EM tarek.bismar@cls.ab.ca
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Smith SC, Tomlins SA, 2014, Prostate cancer SubtyPINg biomarKers and outcome: is clarity emERGing? Clin Cancer Res 20(18):4733–4736., DOI 10.1158/1078-0432.CCR-14-0818
Smith SC, Palanisamy N, Zuhlke KA, Johnson AM, Siddiqui J, Chinnaiyan AM et al, 2014, HOXB13 G84E-related familial prostate cancers: a clinical, histologic, and molecular survey. Am J Surg Pathol 38(5):615–626., DOI 10.1097/PAS.0000000000000090
Gumuskaya B,Gurel B, Fedor H, Tan HL,Weier CA, Hicks JL et al, 2013, Assessing the order of critical alterations in prostate cancer development and progression by IHC: further evidence that PTEN loss occurs subsequent to ERG gene fusion. Prostate Cancer Prostatic Dis 16(2):209–215., DOI 10.1038/pcan.2013.8
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 399
EP 407
DI 10.1007/s12253-016-0119-9
PG 9
ER
PT J
AU Arik, D
Can, C
Dundar, E
Kabukcuoglu, S
Pasaoglu,
AF Arik, Deniz
Can, Cavit
Dundar, Emine
Kabukcuoglu, Sare
Pasaoglu, Ozgul
TI Prognostic Significance of CD24 in Clear Cell Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clear cell renal cell carcinoma; Cancer stem cell marker; CD24; Prognosis
ID Clear cell renal cell carcinoma; Cancer stem cell marker; CD24; Prognosis
AB The role of cancer stem cells in the initiation and progression of cancer has become a well-studied area of emerging research, and stem cells with different surface markers have been identified in various types of cancer. CD24 is a membrane protein that acts as the ligand for Pselectin and has been defined as a stem cell marker of colonic cancer. The immunohistochemical expression of CD24 is associated with worse patient outcomes in small cell lung cancer, hepatocellular carcinoma, breast cancer, and colon cancer. In this study, we used immunohistochemistry to determine CD24 expression in clear cell, papillary and chromophobe renal cell carcinoma and investigated its relationship with other clinicopathological parameters and prognosis. A total of 108 cases of clear cell, 12 papillary and 13 choromophobe renal cell carcinoma were examined. Clinicopathological features including age, gender, vascular invasion, tumor necrosis, and T stage were recorded. Clinical stage and overall survival and disease-free survival times were recorded. The immunohistochemical expression of CD24 was classified as low or high based on the percentage and intensity of positive staining. CD24 expression was associated with both tumor grade and recurrence rates. The survival analysis revealed that patients with high CD24 expression exhibited significantly lower overall and disease-free survival. Increased expression of CD24 is related to the prognosis of clear cell renal cell carcinoma. This is the first study identifying a strong association between CD24 expression levels and survival. Thus, CD24 expression may aid in predicting prognosis in clear cell renal cell carcinoma.
C1 [Arik, Deniz] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Meselik Kampusu, 26480 Eskisehir, Turkey.
[Can, Cavit] Eskisehir Osmangazi University, Faculty of Medicine, Department of UrologyEskisehir, Turkey.
[Dundar, Emine] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Meselik Kampusu, 26480 Eskisehir, Turkey.
[Kabukcuoglu, Sare] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Meselik Kampusu, 26480 Eskisehir, Turkey.
[Pasaoglu, Ozgul] Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Meselik Kampusu, 26480 Eskisehir, Turkey.
RP Arik, D (reprint author), Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, 26480 Eskisehir, Turkey.
EM denarik@hotmail.com
CR Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F, 2015, International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol 67:519–530
Sun C, Song H, Zhang H, Hou C, Zhai T, Huang L, Zhang L, 2012, CD133 expression in renal cell carcinoma, RCC, is correlated with nuclear hypoxia-inducing factor 1α, HIF-1α). J Cancer Res Clin Oncol 138:1619–1624
Axelson H, Johansson ME, 2013, Renal stem cells and their implications for kidney cancer. Semin Cancer Biol 23:56–61
Carrasco E, Alvarez PJ, Prados J, Melguizo C, Rama AR, Aranega A, Rodriguez-Serrano F, 2014, Cancer stem cells and their implication in breast cancer. Eur J Clin Investig 44:678–687
Guler G, Balci S, Costinean S, Ussakli CH, Irkkan C, Suren D, Sari E, Altundag K, OzisikY, Jones S, Bacher J, Shapiro CL, Huebner K, 2012, Stem cell-related markers in primary breast cancers and associated metastatic lesions. Mod Pathol 25:949–955
Bane A, Viloria-Petit A, Pinnaduwage D, Mulligan AM, O’Malley FP, Andrulis IL, 2013, Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers. Breast Cancer Res Treat 140:195–205
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF, 2003, Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB, 2003, Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, BirnbaumD,WichaMS, Dontu G, 2007, ALDH1 is amarker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567
Chen M, Geng J, 2006, P-selectinmediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp 54:75–84
Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP, 2005, CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 65:10783–10793
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DengW, Gu L, Li X, Zheng J, Zhang Y, Duan B, Cui J, Dong J, Du J, 2016, CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. J Transl Med 14:32
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Droz D, Zachar D, Charbit L, Gogusev J, Chretein Y, Iris L, 1990, Expression of the human nephron differentiation molecules in renal cell carcinomas. Am J Pathol 137:895–905
Lee HJ, Kim DI, Kwak C, Ku JH, Moon KC, 2008, Expression of CD24 in clear cell renal cell carcinoma and its prognostic significance. Urol 72:603–607
Wu JX, Zhao YY, Wu X, An HX, 2014, Clinicopathological and prognostic significance of CD24 overexpression in patients with gastric cancer: a meta-analysis. PLoS One 9:e114746
Senner V, Sturm A, Baur I, Schrell UH, Distel L, PaulusW, 1999, CD24 promotes invasion of glioma cells in vivo. J Neuropathol Exp Neurol 58:795–802
Friederichs J, Zeller Y, Hafezi-Moghadam A, Grone HJ, Ley K, Altevogt P, 2000, The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. Cancer Res 60: 6714–6722
Tanaka T, Terai Y, Kogata Y, Ashihara K, Maeda K, Fujiwara S, Yoo S, Tanaka Y, Tsunetoh S, Sasaki H, Kanemura M, Tanabe A, Ohmichi M, 2015, CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer. Oncol Rep 34:2282–2288
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 409
EP 416
DI 10.1007/s12253-016-0128-8
PG 8
ER
PT J
AU Docs, O
Hegyi, K
Mokanszky, A
Monusne, A
Beke, L
Andras, Cs
Bedekovics, J
Mehes, G
AF Docs, Otto
Hegyi, Katalin
Mokanszky, Attila
Monusne, Aniko
Beke, Livia
Andras, Csilla
Bedekovics, Judit
Mehes, Gabor
TI Mutant KRAS Status Is Associated with Increased KRAS Copy Number Imbalance: a Potential Mechanism of Molecular Heterogeneity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Amplification; CEP12; Colorectal cancer; Heterogeneity; KRAS
ID Amplification; CEP12; Colorectal cancer; Heterogeneity; KRAS
AB Mutation rates determined by allele-specific PCR can be highly different in KRAS exon 2 mutant colorectal carcinoma (CRC) samples suggesting intratumoural heterogeneity. To address the effect of KRAS gene copy number on the relative mutant allele frequency the KRAS locus was individually quantified following FISH analysis in 36 cases. We observed, that mutant KRAS status was associated with an elevated KRAS locus number (2.36 ± 0.42 vs 2.63 ± 0.75; p = 0.037) reflecting an increased aneuploidy status but no true amplification of the locus. In parallel, KRAS locus copy numbers showed significant intercellular variability (1–16 copies/cell nucleus) within individual tumours also indicating to a dynamic intratumoural oscillation of the mutant allele copy number. In conclusion, aneusomy is a common feature of KRAS mutant CRC and KRAS copy number variations may have an impact on the relative mutant allele frequency detected by allele specific PCR/sequencing), potentially leading to subclonal diversity and influencing tumour behaviour.
C1 [Docs, Otto] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Hegyi, Katalin] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Mokanszky, Attila] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Monusne, Aniko] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Beke, Livia] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Andras, Csilla] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Bedekovics, Judit] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Mehes, G (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4032 Debrecen, Hungary.
EM gabor.mehes@med.unideb.hu
CR Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A, 2009, Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 205(12):858–862
Lievre A, Bachet JB, Le Corre D et al, 2006, KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66(8):3992–3995
van Krieken JH, Jung A, Kirchner T et al, 2008, KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453(5):417–431
Amado RG, Wolf M, Peeters M et al, 2008, Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634
Karapetis CS, Khambata-Ford S, Jonker DJ et al, 2008, K-ras mutations and benefit fromcetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765
Yu S, Xiao X, Lu J, Qian X, Liu B, Feng J, 2013, Colorectal Cancer Patients with Low Abundance of KRAS Mutation May Benefit from EGFR Antibody Therapy. PLoS One 8(7)
Docs O, Fazakas F, Horvath NL et al, 2015, Changes of KRAS exon 2 codon 12/13 mutation status in recurrent colorectal cancer. Pathol Oncol Res 21(2):399–404
Bakhoum SF, Compton DA, 2012, Chromosomal instability and cancer: a complex relationship with therapeutic potential. J Clin Invest 122(4):1138–1143
Orum H, Nielsen PE, Egholm M, Berg RH, Buchardt O, Stanley C, 1993, Single base pair mutation analysis by BNA directed PCR clamping. Nucleic Acids Res 21(23):5332–5336
Cappuzzo F, Hirsch FR, Rossi E et al, 2005, Epidermal growth factor receptor Gene and Protein and Gefitinib sensitivity in non– small-cell lung cancer. J Natl Cancer Inst 97(9):643–655
Fehrmann RS, Karjalainen JM, Krajewska M et al, 2015, Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat Genet 47(2):115–125
Moroni M, Veronese S, Benvenuti S et al, 2005, Gene copy number for epidermal growth factor receptor, EGFR, and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6(5):279–286
Seth R, Crook S, Ibrahem S, Fadhil W, Jackson D, Ilyas M, 2009, Concomitant mutations and splice variants in KRAS and BRAF demonstrate complex perturbation of the ras/Raf signalling pathway in advanced colorectal cancer. Gut 58(9): 1234–1241
Valtorta E, Misale S, Sartore-Bianchi A et al, 2013, KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer 133(5): 1259–1265
Herrera LA, Prada D, Andonegui MA, Gonzalez AD, 2008, The epigenetic origin of aneuploidy. Curr Genomics 9(1):43–50
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Soh J, Okumura N, Lockwood WW et al Oncogene mutations, copy number gains and mutant allele specific imbalance, MASI, frequently occur together in tumour cells. PLoS One s4(10):e7464
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 417
EP 423
DI 10.1007/s12253-016-0126-x
PG 7
ER
PT J
AU Shinagawa, K
Yanamoto, S
Naruse, T
Kawakita, A
Morishita, K
Sakamoto, Y
Rokutanda, S
Umeda, M
AF Shinagawa, Kenichi
Yanamoto, Souichi
Naruse, Tomofumi
Kawakita, Akiko
Morishita, Kota
Sakamoto, Yuki
Rokutanda, Satoshi
Umeda, Masahiro
TI Clinical Roles of Interleukin-6 and STAT3 in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Il-6; STAT3; Oral squamous cell carcinoma; Lymphangiogenesis
ID Il-6; STAT3; Oral squamous cell carcinoma; Lymphangiogenesis
AB The effect inflammation has on cancer prognosis is marked by the presence of cytokines and chemokines. Interleukin-6 (IL-6) is one a multifunctional cytokine that regulates inflammatory responses.We investigated the roles of IL- 6 and STAT3 and examined the relationship between IL-6 signaling and clinicopathological factors in patients with oral squamous cell carcinoma (OSCC). We retrospectively examined 116 patientswho underwent radical surgery for OSCC. IL- 6 and STAT3 expression were detected by immunohistochemistry. IL-6 and STAT3 positivity were detected by IHC, at 78.4 and 80.2 %, respectively. IL-6 expression was significantly associated with pattern of invasion (P = 0.004), vascular invasion (P = 0.003), and pathological nodal status (P = 0.019). Multivariate logistic regression analysis revealed that IL-6 expression was significantly associated with vascular invasion (P = 0.044). Meanwhile, there was no significant association between STAT3 expression and clinicopathological factors and no significant relationship between IL-6 and STAT3 expression. IL-6 expression was significantly associated with 5-year disease-free survival. These results suggest that IL-6 is involved in lymphangiogenesis and recurrence in OSCC.
C1 [Shinagawa, Kenichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Kawakita, Akiko] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Morishita, Kota] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Sakamoto, Yuki] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Rokutanda, Satoshi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
RP Yanamoto, S (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM syana@nagasaki-u.ac.jp
CR Fitzmaurice C, Dicker D, Pain A et al, 2015, The global burden of cancer 2013. JAMA Oncol 1:505–527
Rogers SN, Brown JS,Woolgar JA et al, 2009, Survival following primary surgery for oral cancer. Oral Oncol 45:201–211
Turcotte S, Rosenberg SA, 2011, Immunotherapy for metastatic solid cancers. Adv Surg 45:341–360
Bell RB, Leidner R, Feng Z et al, 2015, Developing an immunotherapy strategy for the effective treatment of oral, head and neck squamous cell carcinoma. J Oral Maxillofac Surg 73:S107–S115
Chen HH, Chen IH, Liao CT et al, 2011, Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: a retrospective clinical study. Clin Otolaryngol 36:147–153
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Fang HY, Huang XY, Chien HT et al, 2013, Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma. Laryngoscope 123:2690–2699
Culig Z, 2013, Interleukin-6 as a therapy target in oral squamous carcinoma. Expert Opin Ther Targets 17:53–59
Jinno T, Kawano S, Maruse Yet al, 2015, Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma. Oncol Rep 33:2161–2168
Sato J, Ohuchi M, Wada M et al, 2015, Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: part III of a cohort study. Oral Surg Oral Med Oral Pathol Oral Radiol 120:751–760
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Heikkila K, Ebrahim S, Lawlor DA, 2007, A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health 61:824–833
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Yu H, Pardoll D, Jove R, 2009, STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9:798–809
Kruse AL, Luebbers HT, Gratz K et al, 2010, C-reactive protein levels: a prognostic marker for patients with head and neck cancer? Head Neck Oncol 2:21
Neurath MF, Finotto S, 2011, IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev 22:83–89
Paramanathan A, Saxena A, Morris DL, 2014, A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol 23:31–39
Perisanidis C, Kornek G, Poschl PWet al, 2013, High neutrophilto- lymphocyte ratio is an independent marker of poor diseasespecific survival in patients with oral cancer. Med Oncol 30:334
de Oliveira MV, Fraga CA, Gomez RS et al, 2009, Immunohistochemical expression of interleukin-4, −6, −8, and −12 in inflammatory cells in surrounding invasive front of oral squamous cell carcinoma. Head Neck 31:1439–1446
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Shinriki S, Jono H, Ueda M et al, 2011, Interleukin-6 signaling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma. J Pathol 225:142–150
Yadav A, Kumar B, Datta J et al, 2011, IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the LAK-STAT3-SNAIL signaling pathway. Mol Cancer Res 9:1658–1667
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Omoto I, Matsumoto M, Okumura H et al, 2014, Expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 in esophageal squamous cell carcinoma. Oncol Lett 7:1027–1032
Arinaga M, Noguchi T, Takeno S et al, 2003, Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer 97:457–464
Wakisaka N, Hirota K, Kondo S et al, 2012, Induction of lymphangiogenesis through vascular endothelial growth factor-C/ vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma. Oral Oncol 48:703–708
Duffy SA, Taylor JMG, Terrell JE et al, 2008, Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer 113:750–757
Jablonska J, Leschner S, Westphal K et al, 2010, Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest 120:1151–1164
Li MX, Liu XM, Zhang XF et al, 2014, Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 134:2403–2413
Shen L, Zhang H, Liang L et al, 2014, Baseline neutrophillymphocyte ratio, ≥2.8, as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation. Radiat Oncol 9:295
Kim IY, You SH, Kim YW, 2014, Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer. BMC Surg 14:94
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 425
EP 431
DI 10.1007/s12253-016-0134-x
PG 7
ER
PT J
AU Ikegawa, Sh
Doki, N
Kaito, S
Kurosawa, Sh
Sakaguchi, M
Harada, K
Yamamoto, K
Hino, Y
Shingai, N
Senoo, Y
Watanabe, D
Hagino, T
Yoshioka, K
Watakabe, K
Igarashi, A
Najima, Y
Kobayashi, T
Kakihana, K
Sakamaki, H
Ohashi, K
AF Ikegawa, Shuntaro
Doki, Noriko
Kaito, Satoshi
Kurosawa, Shuhei
Sakaguchi, Masahiro
Harada, Kaito
Yamamoto, Keita
Hino, Yutaro
Shingai, Naoki
Senoo, Yasushi
Watanabe, Daisuke
Hagino, Takeshi
Yoshioka, Kosuke
Watakabe, Kyoko
Igarashi, Aiko
Najima, Yuho
Kobayashi, Takeshi
Kakihana, Kazuhiko
Sakamaki, Hisashi
Ohashi, Kazuteru
TI Central Nervous System Involvement at the Time of Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with a Poor Outcome in Patients with Acute Myeloid Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Central nervous system involvement; Allogeneic hematopoietic stem cell transplantation; Acute myeloid leukemia
ID Central nervous system involvement; Allogeneic hematopoietic stem cell transplantation; Acute myeloid leukemia
AB Recent reports suggested that central nervous system (CNS) involvement (CNS+) in patients with acute myeloid leukemia (AML) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not an independent predictor of survival after allo-HSCT. However, these studies did not analyze minimal residual disease in the CNS at the time of allo-HSCT. We evaluated the effect of residual CNS+ on the transplant outcomes of 214 AML patients in a single institution. Twenty-one (10%) patients were diagnosed with CNS+ prior to allo-HSCT. Of these, 13 patients had CNS disease at the time of allo-HSCT. The patients in CNS+ AML remission at the time of allo-HSCT had better overall survival (OS) than the patients who were not in remission (2-year OS: 55% vs. 7.7%, p = 0.0001). In multivariate analyses, CNS+ at the time of allo- HSCT (hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.05–3.59; p = 0.04), age over 50 years at the time of allo-HSCT, and non-complete remission disease status in bone marrow at the time of allo-HSCT were independent adverse factors for OS. However, a prior history of CNS+ before allo-HSCT did not independently affect OS (HR, 1.27; 95% CI 0.53–2.07; p = 0.6). Early diagnosis and eradication of CNS+ at the time of allo-HSCT may be necessary to improve the outcome for patients with CNS+ AML.
C1 [Ikegawa, Shuntaro] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Doki, Noriko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kaito, Satoshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kurosawa, Shuhei] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakaguchi, Masahiro] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Harada, Kaito] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Yamamoto, Keita] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Hino, Yutaro] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Shingai, Naoki] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Senoo, Yasushi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Watanabe, Daisuke] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Hagino, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Yoshioka, Kosuke] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Watakabe, Kyoko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Igarashi, Aiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Najima, Yuho] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kobayashi, Takeshi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Kakihana, Kazuhiko] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Sakamaki, Hisashi] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
[Ohashi, Kazuteru] Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan.
RP Doki, N (reprint author), Komagome Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center, Hematology Division, 113-8677 Tokyo, Japan.
EM n-doki@cick.jp
CR Bommer M, von Harsdorf S, Dohner H, Bunjes D, Ringhoffer M, 2010, Neoplastic meningitis in patients with acute myeloid leukemia scheduled for allogeneic hematopoietic stem cell transplantation. Haematologica 11:1969–1972
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Mayadev JS,Douglas JG, Storer BE, Appelbaum FR, Storb R, 2011, Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement. Int J Radiat Oncol Biol Phys 80:193–198
Aoki J, Ishiyama K, Taniguchi S et al, 2014, Outcome of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with central nervous system involvement. Biol Blood Marrow Transplant 20:2029–2033
Bar M, Tong W, Othus M, Loeb KR, Estey EH, 2015, Central nervous system involvement in acute myeloid leukemia patients undergoing hematopoietic cell transplantation. Biol Blood Marrow Tranplant 21:546–551
Pui CH, Thiel E, 2009, Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol 36:S2–S16
Ruutu T, Corradini P, Gratwohl A et al, 2005, Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation EBMT. Bone Marrow Transplant 35:121–124
Oshima K, Kanda Y, Yamashita T et al, 2008, Central nervous system relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 14:1100–1107
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 433
EP 437
DI 10.1007/s12253-016-0162-6
PG 5
ER
PT J
AU Zhang, YY
Wang, QM
Niu, HL
Liu, X
Zhang, QL
AF Zhang, Yao-Yao
Wang, Qi-Ming
Niu, Hui-Lin
Liu, Xia
Zhang, Qing-Ling
TI The General Expression Analysis of WTX Gene in Normal and Cancer Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Wilms’ tumor suppressorX chromosome (WTX); Tumor suppressor; Immunohistochemical staining; In situ hybridization
ID Wilms’ tumor suppressorX chromosome (WTX); Tumor suppressor; Immunohistochemical staining; In situ hybridization
AB WTX (Wilms’ tumor suppressor X chromosome) is a novel putative tumor suppressor gene in Wilms’ tumor of kidney, its expression and function in other human cancers had not been explored. This study detected the expression of WTX in 459 cases of 15 organs of cancers and adjacent normal tissues by using immunohistochemical staining (IHC), and validated them by in situ hybridization (ISH) and quantitative real-time reverse transcription PCR (qRT-PCR). IHC and ISH data showed that WTX protein was generally expressed in normal tissues, but reduced expression in corresponding cancers. This study demonstrated that WTX downregulation is a common phenomenon in human cancers, WTX might be a general tumor-suppressor gene and biological marker of multiple cancer tissues. Apart from kidney, stomach is another target tissue of WTX gene. The germline and somatic mutations of WTX were screened in 12 gastric cancer patients and identified in one cases (8.3%). Mutation in the WTX gene might be one of the reasons of WTX loss in gastric cancer patients.
C1 [Zhang, Yao-Yao] Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
[Wang, Qi-Ming] Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
[Niu, Hui-Lin] Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
[Liu, Xia] Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
[Zhang, Qing-Ling] Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
RP Zhang, QL (reprint author), Nanfang Hospital, Department of Pathology, 510515 Guangzhou, China.
EM zqllc8@126.com
CR Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, FeinbergAP, GeraldWL,Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA, 2007, An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 315(5812):642–645
Alexandrescu, S., S. Akhavanfard, M.H. Harris, and S.O. Vargas, Clinical, pathologic, and genetic features of Wilms tumors with WTX gene mutation. Pediatr Dev Pathol, 2016.
X-ing Out Tumor Suppression. Science, 2007. 315: p. 569 h.
Bagchi S, 2007, New tumour suppressor linked toWilms’ tumour. Lancet Oncol 8(2):102
KimMK, Min DJ, Rabin M, Licht JD, 2011, Functional characterization ofWilms tumor-suppressorWTX and tumor-associated mutants. Oncogene 30(7):832–842
Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, Thaller C, Hing AV, Porteous ME, Garcia-Minaur S, Bohring A, Lacombe D, Stewart F, Fiskerstrand T, Bindoff L, Berland S, Ades LC, Tchan M, David A, Wilson LC, Hennekam RC, Donnai D, Mansour S, Cormier-Daire V, Robertson SP, 2009, Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet 41(1):95–100
Fujita A, Ochi N, Fujimaki H, Muramatsu H, Takahashi Y, Natsume J, Kojima S, Nakashima M, Tsurusaki Y, Saitsu H, Matsumoto N, Miyake N, 2014, A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. Am J Med Genet A 164A(4):998–1002
Comai G, Boutet A, Neirijnck Y, Schedl A, 2010, Expression patterns of theWtx/Amer gene family during mouse embryonic development. Dev Dyn 239(6):1867–1878
He L, Ding Y, Zhang Q, Che X, He Y, Shen H,Wang H, Li Z, Zhao L, Geng J, Deng Y, Yang L, Li J, Cai J, Qiu L,Wen K, Xu X, Jiang S, 2006, Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 210(3):288–297
Qingling Z, Lina Y, Li L, ShuangW, Yufang Y, Yi D, Divakaran J, Xin L, Yanqing D, 2011, LMP1 antagonizes WNT/beta-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8, transgenic mice. J Pathol 223(5):574–583
MajorMB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, Biechele TL, Gingras AC, Zheng N, Maccoss MJ, Angers S,Moon RT, 2007, Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science 316(5827):1043–1046
Livak KJ, Schmittgen TD, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T), method. Methods 25(4):402–408
Armat M, Ramezani F, Molavi O, Sabzichi M, Samadi N, 2016, Six family of homeobox genes and related mechanisms in tumorigenesis protocols. Tumori:0
Kress E, Skah S, Sirakov M, Nadjar J, Gadot N, Scoazec JY, Samarut J, Plateroti M, 2010, Cooperation between the thyroid hormone receptor TRalpha1 and theWNT pathway in the induction of intestinal tumorigenesis. Gastroenterology 138(5):1863–1874
Rivlin N, Brosh R, Oren M, Rotter V, 2011, Mutations in the p53 tumor suppressor Gene: importantmilestones at the various steps of tumorigenesis. Genes Cancer 2(4):466–474
Holloway KR, Sinha VC, Bu W, Toneff M, Dong J, Peng Y, Li Y, 2016, Targeting oncogenes into a defined subset ofmammary cells demonstrates that the initiating oncogenic mutation defines the resulting tumor phenotype. Int J Biol Sci 12(4):381–388
ZhouQM, LiW, Zhang X, Chen YB, Chen XC, Guan YX, Ding Y, Wen XZ, Xia Q, Zhou Q, Peng RQ, Hou JH, Zhu XF, Zeng YX, Zhang XS, 2012, The mutation profiles of common oncogenes involved in melanoma in southern China. J Invest Dermatol 132(7):1935–1937
Evangelisti C, de Biase D, Kurelac I, Ceccarelli C, Prokisch H, Meitinger T, Caria P, Vanni R, Romeo G, Tallini G, Gasparre G, Bonora E, 2015, A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors. BMC Cancer 15:157
Perotti D, Gamba B, SardellaM, Spreafico F, Terenziani M, Collini P, Pession A, Nantron M, Fossati-Bellani F, Radice P, 2008, Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors. Oncogene 27(33):4625–4632
Fukuzawa R, Holman SK, Chow CW, Savarirayan R, Reeve AE, Robertson SP, 2010)WTX mutations can occur both early and late in the pathogenesis ofWilms tumour. J Med Genet 47(11):791–794
Scheel SK, Porzner M, Pfeiffer S, Ormanns S, Kirchner T, Jung A, 2010, Mutations in the WTX-gene are found in some high-grade microsatellite instable, MSI-H, colorectal cancers. BMC Cancer 10:413
Chung NG, Kim MS, Chung YJ, Yoo NJ, Lee SH, 2008, Tumor suppressor WTX gene mutation is rare in acute leukemias. Leuk Lymphoma 49(8):1616–1617
Zilberman D, Coleman-Derr D, Ballinger T, Henikoff S, 2008, Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456(7218):125–129
Liu X, Wang Q, Niu H, Yang X, Sun J, Zhang Q, Ding Y, 2013, Promotermethylation ofWilms’ tumor gene on the X- chromosome in gastric cancer. Nan Fang Yi Ke Da Xue Xue Bao 33(3):318–321
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 439
EP 446
DI 10.1007/s12253-016-0168-0
PG 8
ER
PT J
AU Woyen, VTA
Laczko, G
Hoyer, S
Hegyi, L
AF Woyen, Vidar Tind Arne
Laczko, Gergely
Hoyer, Soren
Hegyi, Laszlo
TI The Missing Link in the Diagnostic Pathway of Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostatic carcinoma; Adenocarcinoma; Small cell carcinoma; Immunohistochemistry
ID Prostatic carcinoma; Adenocarcinoma; Small cell carcinoma; Immunohistochemistry
AB Prostate cancer is one of the most common cancers in the Western world. It is among the leading causes of cancer related death. While its incidence and survival increased significantly during the last few decades in Denmark, the mortality rate did not change for patients younger than 80 year old. Development of new techniques, such as multiparametric MRI, helps to increase the accuracy of diagnosis. However, a missing link in the diagnostic pathway may result in mistreatment if an acinar adenocarcinoma of prostate is transformed into a neuroendocrine phenotype such as small cell carcinoma.
C1 [Woyen, Vidar Tind Arne] Regionshospitalet Viborg, Patologisk Institut, Pakhusvej 1, 8800 Viborg, Denmark.
[Laczko, Gergely] Regionshospitalet Viborg, Urologisk AfdelingViborg, Denmark.
[Hoyer, Soren] Aarhus Universitetshospital, Patologisk InstitutAarhus, Denmark.
[Hegyi, Laszlo] Regionshospitalet Viborg, Patologisk Institut, Pakhusvej 1, 8800 Viborg, Denmark.
RP Hegyi, L (reprint author), Regionshospitalet Viborg, Patologisk Institut, 8800 Viborg, Denmark.
EM lhegyi@doctors.org.uk
CR Cookson MS, Roth BJ, Dahm P, et al., 2015, Castration-Resistant Prostate Cancer. AUA Guideline. In AUA Guidelines https://www. auanet.org/education/guidelines/castration-resistant-prostatecancer. cfm. Accessed 27 June 2016
Mottet N, Bellmunt J, Briers E, et al., 2016, Prostate Cancer. https://uroweb.org/guideline/prostate-cancer/. Accessed 27 June 2016
Palmgren JS, Karavadia SS, Wakefield MR, 2007, Unusual and underappreciated: small cell carcinoma of the prostate. Semin Oncol 34:22–29
Spiess PE, Pettaway CA, Vakar-Lopez F et al, 2007, Treatment outcomes of small cell carcinoma of the prostate: a single-center study. Cancer 110:1729–1737
Li Z, Sun Y, Chen X et al, 2015, P 53 mutation directs AURKA overexpression via miR-25 and FBXW7 in prostatic small cell neuroendocrine carcinoma. Mol Cancer Res 13:584–591
Terry S, Beltran H, 2014, The many faces of neuroendocrine differentiation in prostate cancer progression. Front Oncol 4:60
Burchardt T, Burchardt M, ChenMWet al, 1999, Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo. J Urol 162:1800–1805
Santoni M, Conti A, Burattini L et al, 2014, Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta 1846:630– 637
Vlachostergios PJ, Papandreou CN, 2015, Targeting neuroendocrine prostate cancer: molecular and clinical perspectives. Front Oncol 5:6
Small EJ, Huang J, Youngren J, et al., 2015, Characterization of neuroendocrine prostate cancer, NEPC, in patients with metastatic castration resistant prostate cancer, mCRPC, resistant to abiraterone, Abi, or enzalutamide, Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team, WCDT). 2015 ASCO Annual Meeting. http://meetinglibrary. asco.org/content/152182-156. Accessed 27 June 2016
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 447
EP 450
DI 10.1007/s12253-016-0183-1
PG 4
ER
PT J
AU Lee, HJ
Kim, SS
Kim, SM
Yoo, JN
Lee, HS
AF Lee, Hwa Ju
Kim, Soo Sung
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI WRN, the Werner Syndrome Gene, Exhibits Frameshift Mutations in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Lee, Hwa Ju] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Soo Sung] The Catholic University of Korea, College of Medicine, Department of Internal MedicineSeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Futami K, IshikawaY, Goto M, Furuichi Y, SugimotoM(2008, Role of Werner syndrome gene product helicase in carcinogenesis and in resistance to genotoxins by cancer cells. Cancer Sci 99:843–848
Goto M, Miller RW, Ishikawa Y, Sugano H, 1996, Excess of rare cancers in Werner syndrome, adult progeria,, 1996, J. Cancer Epidemiol Biomark Prev 5:239–246
Shimamoto A, Sugimoto M, Furuichi Y, 2004, Molecular biology of Werner syndrome 2004. Int J Clin Oncol 9:288–298
Yamagata K, Kato J, Shimamoto A, Goto M, Furuichi Y, Ikeda H, 1998, Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases. Proc Natl Acad Sci U S A 95: 8733–8738
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Choi MR, Gwak M, Yoo NJ, Lee SH, 2015, Regional bias of Intratumoral genetic heterogeneity of apoptosis-related genes BAX, APAF1, and FLASH in Colon cancers with high microsatellite instability. Dig Dis Sci 60:1674–1679
Kim TM, Jung SH, An CH, Lee SH, Baek IP, Kim MS, Park SW, Rhee JW, Lee SH, Chung YJ, 2015, Subclonal genomic architectures of primary and metastatic colorectal cancer based on Intratumoral genetic heterogeneity. Clin Cancer Res 21:4461–4472
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 451
EP 452
DI 10.1007/s12253-016-0173-3
PG 2
ER
PT J
AU Jo, SY
Kim, SS
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Soo Sung
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Frameshift Mutation of FXR1 Encoding a RNA-Binding Protein in Gastric and Colorectal Cancers with Microsatellite Instability
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE FXR1; Frameshift mutation; Tumor suppressor gene; Intrarumoral heterogeneity
ID FXR1; Frameshift mutation; Tumor suppressor gene; Intrarumoral heterogeneity
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Soo Sung] The Catholic University of Korea, College of Medicine, Department of Internal MedicineSeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Raheja R, Gandhi R, 2016, FXR1: linking cellular quiescence, immune genes and cancer. Cell Cycle 15:2695–2696
Vasudevan S, Steitz JA, 2007, AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 128:1105–1118
Qian J, HassaneinM, HoeksemaMD, Harris BK, Zou Y, Chen H, Lu P, Eisenberg R, Wang J, Espinosa A, Ji X, Harris FT, Rahman SM, Massion PP, 2015, The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers. Proc Natl Acad Sci U S A 112:3469–3474
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Oh HR, An CH, Yoo NJ, Lee SH, 2015, Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in gastric and colorectal cancers. Pathol Oncol Res 21:713–718
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 453
EP 454
DI 10.1007/s12253-016-0177-z
PG 2
ER
PT J
AU Robert, L
Labat-Robert, J
AF Robert, Ladislas
Labat-Robert, Jacqueline
TI Platelets, Micro-Particles and Elastase. A Review with Extrapolation to the Mechanism of Generation and Bio-Pathology of Platelet Fragments
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Robert, Ladislas] Hopital Hotel Dieu, Laboratoire de Recherche OphtalmologiqueParis, France.
[Labat-Robert, Jacqueline] Hopital Hotel Dieu, Laboratoire de Recherche OphtalmologiqueParis, France.
RP Robert, L (reprint author), Hopital Hotel Dieu, Laboratoire de Recherche Ophtalmologique, Paris, France.
EM lrobert5@orange.fr
CR Schiro A, Wilkinson RL, Weston R, Smyth V, Serracino-Inglott F, Alexander MY, 2015, Elevated levels of endothelial-derived microparticles, and serum CXCL9 and SCGF-β are associated with unstable asymptomatic carotid plaques. www.nature.Scientific Reports DOI:10.1038/srep16658
Dovizio M, Alberti S, Sacco A, Guillem-Llobat P, Schiavone S, Maier TJ, Steinhilber D, Patrignani P, 2015, Novel insights in the regulation of cyclooxygenase expression by platelet-cancer cell cross-talk. Biochem Soc Trans 43:707–714
Robert B, Legrand Y, Pignaud G, Caen J, Robert L, 1969, Activite elastolytique associee aux plaquettes sanguines. Pathol Biol 17: 615–622
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Legrand Y, Robert B, Szigeti M, Pignaud G, Caen J, Robert L, 1970, Etudes sur une protease elastinolytique des plaquettes sanguines humaines. Atherosclerosis 12:451–465
Robert B, Robert L, Legrand Y, Pignaud G, Caen J, 1971, Elastolytic protease in blood platelets. Ser Haemat 4:175–185
Robert B, Legrand Y, Soria C, Caen J, Robert L, 1972, Etude sur les proteases des plaquettes sanguines humaines: purification d’une elastase. C R Acad Sci 274:1749–1752
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 455
EP 458
DI 10.1007/s12253-017-0199-1
PG 4
ER
PT J
AU Kireeva, G
Bespalov, GV
Belyaeva, AO
Senchik, K
Stukov, NA
Gafton, G
Guseynov, K
Belyaev, A
AF Kireeva, S. Galina
Bespalov, Grigorievich Vladimir
Belyaeva, Alexandrovna Olesya
Senchik, Y. Konstantin
Stukov, Nikolayevich Aleksandr
Gafton, I. Georgiy
Guseynov, D. Konstantin
Belyaev, M. Alexey
TI Normothermic and Hyperthermic Intraperitoneal Chemoperfusions with Cisplatin to Treat Advanced Ovarian Cancer in Experimental Settings
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kireeva, S. Galina] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Bespalov, Grigorievich Vladimir] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Belyaeva, Alexandrovna Olesya] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Senchik, Y. Konstantin] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Stukov, Nikolayevich Aleksandr] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Gafton, I. Georgiy] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Guseynov, D. Konstantin] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
[Belyaev, M. Alexey] Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, Pesochny, Leningradskaya str., 68, 197758 Saint-Petersburg, Russian Federation.
RP Kireeva, G (reprint author), Russian Ministry of Health, N. N. Petrov Research Institute of Oncology, 197758 Saint-Petersburg, Russian Federation.
EM galinakireyeva@mail.ru
CR Sugarbaker PH, 2005, Technical handbook for the integration of cytoreductive surgery and perioperative intraperitoneal chemotherapy into the surgical management of gastrointestinal and gynecologic malignancy, 4th edn. The Ludann, Michigan
Gremonprez F,WillaertW, CeelenW(2014, Intraperitoneal chemotherapy, IPC, for peritoneal carcinomatosis: review of animal models. J Surg Oncol 109:110–116., DOI 10.1002/jso.23464
Sugarbaker PH, 2003, Peritonectomy procedures. Surg Oncol Clin N Am12:703–727
Zeamari S, Floot B, Van der Vange N, Stewart FA, 2003, Pharmacokinetics and pharmacodynamics of cisplatin after intraoperative hyperthermic intraperitoneal chemoperfusion, HIPEC). Anticancer Res 23:1643–1648
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 459
EP 460
DI 10.1007/s12253-017-0202-x
PG 2
ER
PT J
AU Liu, P
Zu, X
Liu, L
AF Liu, Peihua
Zu, Xiongbing
Liu, Longfei
TI Erratum to: Genetic Screening in Pheochromocytoma/ Paraganglioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Erratum to: Pathol. Oncol. Res. (2017) 23:217-217 DOI 10.1007/s12253-016-0117-y The original article contained an error. The corrected Acknowledgements section is shown below. Acknowledgements: This study was supported by the National Natural Science Foundation of China (No.81400773) and Natural Science Foundation of China Hunan Province (No.14JJ6002).
C1 [Liu, Peihua] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
[Zu, Xiongbing] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
[Liu, Longfei] Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, Hunan, China.
RP Liu, L (reprint author), Central South University, Xiangya hospital, Department of Urology, 410008 Changsha, China.
EM longfei_liu@163.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2017
VL 23
IS 2
BP 461
EP 461
DI 10.1007/s12253-017-0210-x
PG 1
ER
PT J
AU Ding, AV
Zhu, Z
Mantz, AA
Xiao, H
Wakefield, RM
Bai, Q
Fang, Y
AF Ding, A Vivi
Zhu, Ziwen
Mantz, A Alyse
Xiao, Huaping
Wakefield, R Mark
Bai, Qian
Fang, Yujiang
TI The Role of IL-37 in Non-Cancerous Diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE IL-37; Non-cancerous diseases
ID IL-37; Non-cancerous diseases
AB IL-37 is a newly discovered cytokine belonging to IL-1 family consisting of 11 members, which have similar β- barrel structures and associate with Ig-like receptors. Extensive studies have been done with IL-37 since its discovery. These studies suggest that IL-37 does not only play a role in tumorigenesis, but also has anti-inflammatory properties in immune responses through the down regulation of proinflammatory molecules. We have previously reviewed the role of IL-37 in cancer. Here, we will focus on the role of IL-37 in non-cancerous Diseases. Such a study might be helpful to design new strategies to treat IL-37 associated diseases.
C1 [Ding, A Vivi] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Mantz, A Alyse] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Xiao, Huaping] The Affiliated Hospital of Xiangnan UniversityChenzhou, Hunan, China.
[Wakefield, R Mark] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Bai, Qian] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
EM yujiang.fang@dmu.edu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 463
EP 470
DI 10.1007/s12253-016-0137-7
PG 8
ER
PT J
AU Lee, HJ
Yoo, JN
Kim, SM
Lee, HS
AF Lee, Hwa Joo
Yoo, Jin Nam
Kim, Sung Min
Lee, Hyung Sug
TI Histone Demethylase Gene PHF2 Is Mutated in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PHF2; Tumor suppressor gene; Frameshift mutation; Cancer; Microsatellite instability; Intratumoral heterogeneity
ID PHF2; Tumor suppressor gene; Frameshift mutation; Cancer; Microsatellite instability; Intratumoral heterogeneity
AB Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we analyzed 124 colorectal cancers (CRCs) and 79 gastric (GCs) cancers for the mutations and their intratumoral heterogeneity (ITH). Twenty-two of 79 CRCs (27.8 %) and 7 of 34 GCs (20.6 %) harboring MSI-H exhibited frameshift mutations. However, we found no such mutations in microsatellite stable/low MSI (MSS/MSI-L) cancers. Also, we studied ITH for the detected frameshift mutations in 16 cases of CRCs and detected ITH in two (12.5 %) cases. Our data reveal that TSG gene PHF2 harbors mutational ITH as well as the frameshift mutations in CRC and GC with MSI-H. Based on this, it is suggested that frameshift mutations of PHF2 may play a role in tumorigenesis through its TSG inactivation in CRC and GC.
C1 [Lee, Hwa Joo] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 471
EP 476
DI 10.1007/s12253-016-0130-1
PG 6
ER
PT J
AU Chang-Lee, NSh
Hsu, HH
Shibu, AM
Ho, TJ
Tsai, ChH
Chen, MCh
Tu, ChCh
Viswanadha, PV
Kuo, WW
Huang, ChY
AF Chang-Lee, Nu Shu
Hsu, Hsi-Hsien
Shibu, Asokan Marthandam
Ho, Tsung-Jung
Tsai, Chih-Hao
Chen, Ming-Cheng
Tu, Chuan-Chou
Viswanadha, Padma Vijaya
Kuo, Wei-Wen
Huang, Chih-Yang
TI E2/ERβ Inhibits PPARα to Regulate Cell-Proliferation and Enhance Apoptosis in Hep3B-Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Estrogen; Estrogen receptor; peroxisome proliferator-activated receptor; Hepatocellular carcinoma
ID Estrogen; Estrogen receptor; peroxisome proliferator-activated receptor; Hepatocellular carcinoma
AB Peroxisome proliferator-activated receptor-α (PPARα) is a member of the nuclear receptor superfamily involved in hepatocarcinogenesis in rodents. In previous studies on liver tumor tissues, PPARα mRNA expression was found to be significantly higher and overexpression of ERα inhibited the PPARα expression, cell-proliferation and also induced apoptosis in Hep3B cell. However, the role of ERβ is not known yet. Therefore, the aim of this study is to define the role of ERβ on PPARα in Hep3B cells. The effect of PPARα signaling cascade were monitored by inducing Hep3B cells by fenofibrate. Further the cells were transfected with pCMV-ERβ and the consequences of ERβ-overexpression on the PPARα induced changes such as enhanced cell-proliferation and suppressed apoptosis were determined using western blot analysis and TUNEL assay. The EMSA was used to identify whether ERβ modulates PPARα expression by binding to PPARα promoter region to repress PPARα promoter activity. In addition, the direct interaction between ERβ and PPARα proteins was verified by co-immunoprecipitation assay. Our results show that the overexpressed ERβ not only attenuated the effects of fenofibrate to induce the levels of apoptosis protein such as Cyt.c, Caspase 9 and Caspase 3 but also inhibited the levels of survival protein such Bcl-xL, p-Bad, cyclin A and cyclin E. All these effects of E2/ERβ resulted in the enhancement of mitochondria dependent apoptotic pathway and the attenuation of cell proliferation. Moreover, the overexpressed ERβ reduced the mRNA and protein levels of PPARα and its downstream Acyl-CoA oxidase (ACO). EMSA results show that ERβ directly binds to PPRE and inhibit PPARα gene expression and according to immunoprecipitation assay ERβ also binds strongly with PPARα. The E2/ERβ further inhibited the fenofibrate-induced nuclear translocation of PPARα. Taken together, ERβ might directly downregulate PPARα gene expression and inhibit the nuclear translocation to suppress the proliferation and induce the apoptosis of Hep3B cells.
C1 [Chang-Lee, Nu Shu] Asia University, Department of Healthcare Administration, 413 Taichung, Taiwan, Republic of China.
[Hsu, Hsi-Hsien] Mackay Memorial Hospital, Division of Colorectal Surgery, 104 Taipei, Taiwan, Republic of China.
[Shibu, Asokan Marthandam] China Medical University, Graduate Institute of Basic Medical Science, 404 Taichung, Taiwan, Republic of China.
[Ho, Tsung-Jung] China Medical University, Graduate Institute of Chinese Medicine, 404 Taichung, Taiwan, Republic of China.
[Tsai, Chih-Hao] China Medical University, Graduate Institute of Basic Medical Science, 404 Taichung, Taiwan, Republic of China.
[Chen, Ming-Cheng] Taichung Veterans General Hospital, Division of Colorectal Surgery, 407 Taichung, Taiwan, Republic of China.
[Tu, Chuan-Chou] Taichung Armed Force General Hospital, Department of Internal Medicine, Division of Chest Medicine, 411 Taichung, Taiwan, Republic of China.
[Viswanadha, Padma Vijaya] Bharathiar University, Department of Biotechnology, 641046 Coimbatore, India.
[Kuo, Wei-Wen] China Medical University, Department of Biological Science and Technology, 402 Taichung, Taiwan, Republic of China.
[Huang, Chih-Yang] China Medical University, Graduate Institute of Basic Medical Science, 404 Taichung, Taiwan, Republic of China.
RP Huang, ChY (reprint author), China Medical University, Graduate Institute of Basic Medical Science, 404 Taichung, Taiwan, Republic of China.
EM cyhuang@mail.cmu.edu.tw
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 477
EP 485
DI 10.1007/s12253-016-0136-8
PG 9
ER
PT J
AU Sahin, N
Akatli, NA
Celik, RM
Ulutas, H
Samdanci, TE
Colak, C
AF Sahin, Nurhan
Akatli, Nur Ayse
Celik, Reha Muhammet
Ulutas, Hakki
Samdanci, Turkmen Emine
Colak, Cemil
TI The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretinin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mesothelioma; CD 90; Pulmonary adenocarcinoma; Squamous cell carcinoma
ID Mesothelioma; CD 90; Pulmonary adenocarcinoma; Squamous cell carcinoma
AB Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.
C1 [Sahin, Nurhan] Inonu University, Turgut Ozal Medical Center, Department of Pathology, 44280 Malatya, Turkey.
[Akatli, Nur Ayse] Inonu University, Turgut Ozal Medical Center, Department of Pathology, 44280 Malatya, Turkey.
[Celik, Reha Muhammet] Inonu University, Turgut Ozal Medical Center, Department of Thoracic SurgeryMalatya, Turkey.
[Ulutas, Hakki] Inonu University, Turgut Ozal Medical Center, Department of Thoracic SurgeryMalatya, Turkey.
[Samdanci, Turkmen Emine] Inonu University, Turgut Ozal Medical Center, Department of Pathology, 44280 Malatya, Turkey.
[Colak, Cemil] Inonu University, Medical Faculty, Department of BiostatisticMalatya, Turkey.
RP Sahin, N (reprint author), Inonu University, Turgut Ozal Medical Center, Department of Pathology, 44280 Malatya, Turkey.
EM sahin.nurhan@gmail.com
CR Gueugnon F, Leclercq S, Blanquart C et al, 2011, Identification of novel markers for the diagnosis ofmalignant pleural mesothelioma. Am J Pathol 178:1033–1042
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 487
EP 491
DI 10.1007/s12253-016-0135-9
PG 5
ER
PT J
AU Gaal, Zs
Olah,
Rejto, L
Erdodi, F
Csernoch, L
AF Gaal, Zsuzsanna
Olah, Eva
Rejto, Laszlo
Erdodi, Ferenc
Csernoch, Laszlo
TI Strong Correlation between the Expression Levels of HDAC4 and SIRT6 in Hematological Malignancies of the Adults
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute myeloid leukemia; Epigenetics; Histone deacetylation; HDAC4; SIRT6
ID Acute myeloid leukemia; Epigenetics; Histone deacetylation; HDAC4; SIRT6
AB Histone deacetylase enzymes, confirmed to have important role in the pathogenesis of leukemia, are promising targets of epigenetic treatment. However, in acute myeloid leukemia, our knowledge on their expression levels is limited, and controversial data have been published about their potential oncogenic or tumorsuppressor properties in solid tumors. In our study, the expression levels of HDAC4 and SIRT6 were evaluated via Western blot analysis in 45 bone marrow samples (2 uninfiltrated and 43 concerned by different kinds of hematological malignancies), including 32 specimens obtained from patients with newly diagnosed AML. Significantly higher HDAC4 level was detected in case of FLT3-ITD mutation compared to the group of patients without carrying this mutation (p < 0.05). Compared to the non-infiltrated samples, the expression level of HDAC4 in AML M5 patients has been proved to be significantly higher (p < 0.05). Decreasing expression levels of both HDAC4 and SIRT6 were observed during the induction treatment of FAB M5 type AML. Strong correlation has been proved between the expression levels of HDAC4 and SIRT6 (r = 0.722 in full cohort and r = 0.794 in AML), that confirms the recently suggested cooperation between NAD+-independent and NAD+-dependent HDAC enzymes in leukemia.
C1 [Gaal, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Olah, Eva] Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Rejto, Laszlo] University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Erdodi, Ferenc] University of Debrecen, Faculty of Medicine, Department of Medical Chemistry, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
[Csernoch, Laszlo] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
RP Rejto, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Internal Medicine, H-4012 Debrecen, Hungary.
EM csl@edu.unideb.hu
CR Haberland M, Montgomery RL, Olson EN, 2009, The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42
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Di Croce L, 2005, Chromatin modifying activity of leukemia associated fusion proteins. Hum Mol Genet 14(Review Issue 1):R77– R84
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 493
EP 504
DI 10.1007/s12253-016-0139-5
PG 12
ER
PT J
AU Koszo, R
Santha, D
Budi, L
Erfan, J
Gyorfy, K
Horvath, Zs
Kocsis, J
Landherr, L
Hitre, E
Mahr, K
Pajkos, G
Papai, Zs
Kahan, Zs
AF Koszo, Renata
Santha, Dora
Budi, Laszlo
Erfan, Jozsef
Gyorfy, Karoly
Horvath, Zsolt
Kocsis, Judit
Landherr, Laszlo
Hitre, Erika
Mahr, Karoly
Pajkos, Gabor
Papai, Zsuzsanna
Kahan, Zsuzsanna
TI Capecitabine in Combination with Docetaxel in First Line in HER2-Negative Metastatic Breast Cancer: an Observational Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Capecitabine; Docetaxel; HER2-negative metastatic breast cancer; Toxicity
ID Capecitabine; Docetaxel; HER2-negative metastatic breast cancer; Toxicity
AB Due to the limited experience with capecitabine plus docetaxel (XT) combination in the first-line treatment of metastatic breast cancer in Hungary, the main objective of the study was to analyze the effectiveness and tolerability of XT therapy. A prospective, open-label, non-randomized, single- arm, multicenter, observational study was designed. All female patients were eligible whose metastatic breast cancer could be treated with the XT protocol according to the summary of product characteristics of the drugs. The median progression free survival was 9.9 ± 3.0 months. Time to treatment failure was 4.6 ± 5.1 months on average. The overall response rate was 28.9 %, the clinical benefit rate was 73.3 %. The treatment was discontinued in 35.6 % of patients due to disease progression and in 20.0%due to adverse events (AE). 33 patients with a total of 73 AEs have been reported, and 13 of them had serious adverse events (SAE). The efficacy and the safety profile of XT chemotherapy proven in the study are consistent with the results demonstrated in randomized trials. First-line XT chemotherapy effectively improves the PFS in metastatic breast cancer.
C1 [Koszo, Renata] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Santha, Dora] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Budi, Laszlo] County Hospital of Borsod-Abauj-Zemplen, Szentpeteri kapu 72-76, 3526 Miskolc, Hungary.
[Erfan, Jozsef] Josa Andras County Hospital, Szent Istvan u. 68, 4400 Nyiregyhaza, Hungary.
[Gyorfy, Karoly] Kaposi Mor Teaching Hospital, Tallian Gy. u. 20-32, 7400 Kaposvar, Hungary.
[Horvath, Zsolt] University of Debrecen, Faculty of Medicine, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kocsis, Judit] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Landherr, Laszlo] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Uzsoki u. 29-41, 1145 Budapest, Hungary.
[Hitre, Erika] National Institute of Oncology, Rath Gyorgy u. 7-9, 1126 Budapest, Hungary.
[Mahr, Karoly] County Hospital of Zala, Zrinyi M. u. 1, 8900 Zalaegerszeg, Hungary.
[Pajkos, Gabor] Bacs-Kiskun County Hospital, Nyiri u. 38, 6000 Kecskemet, Hungary.
[Papai, Zsuzsanna] Honved Korhaz, Robert Karoly korut 44, 1134 Budapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM kahan.zsuzsanna@med.u-szeged.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 505
EP 511
DI 10.1007/s12253-016-0129-7
PG 7
ER
PT J
AU Semjen, D
Farkas, A
Kalman, E
Kaszas, B
Kovacs,
Pusztai, Cs
Szuhai, K
Tornoczky, T
AF Semjen, David
Farkas, Andras
Kalman, Endre
Kaszas, Balint
Kovacs, Arpad
Pusztai, Csaba
Szuhai, Karoly
Tornoczky, Tamas
TI More Cases of Benign Testicular Teratomas are Detected in Adults than in Children. A Clinicopathological Study of 543 Testicular Germ Cell Tumor Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Benign teratoma; Mature teratoma; Germ cell tumor; Testis; Postpubertal; Testicular neoplasms
ID Benign teratoma; Mature teratoma; Germ cell tumor; Testis; Postpubertal; Testicular neoplasms
AB Benign testicular teratomas are always thought to be pediatric neoplasms and previously all the teratoid tumors in the adult testis regarded as malignant. Recently, three publications reported benign testicular teratomas in adulthood and the latest WHO classification refers them as "prepubertal type of teratomas" which rarely appear in adulthood. These neoplasms behave benign and seemingly analogous independently whether they appear in pre- or postpubertal patients. The aim of our study was to investigate the frequency of benign testicular teratomas both in children and adults. 593 cases of testicular neoplasms were found in a period of 17 years ranging from1998 to 2014 in the archive of our department (Department of Pathology, Medical Center, Pecs University). 543 cases diagnosed as germ cell tumor which have all been further evaluated in conjunction with the clinical data available. Of all germ cell tumor cases 14 (2.5 %) were pure teratomas. Ten out of 14 were the WHO-defined "conventional" teratoma, 4 of the 14 were the "benign or the so called prepubertal type" from which three occurred in adult patients. Only one of the 14 occurred in childhood, indicating that benign prepubertal type teratomas –which are regarded generally as childhood tumors- are more frequently detected in adults than in children. Benign adult testicular teratomas comprised 21 % of all pure teratoma cases in our series. Practicioners in the field have to be aware of its existence also in adulthood to avoid overtreatment and not to expose their patients to unnecessary chemotherapy, retroperitoneal lymphadenectomy (RLA) and the potential complications of these interventions.
C1 [Semjen, David] University of Pecs, Department of Pathology, Rakoczi u 2, H-7624 Pecs, Hungary.
[Farkas, Andras] University of Pecs, Department of Pediatrics, Jozsef Attila u. 7, H-7623 Pecs, Hungary.
[Kalman, Endre] University of Pecs, Department of Pathology, Rakoczi u 2, H-7624 Pecs, Hungary.
[Kaszas, Balint] University of Pecs, Department of Pathology, Rakoczi u 2, H-7624 Pecs, Hungary.
[Kovacs, Arpad] Pecs University, Faculty of Health Sciences, Department of Diagnostic, Voromarty u. 4, H-7621 Pecs, Hungary.
[Pusztai, Csaba] University of Pecs, Department of Urology, Munkacsy M. u. 2, H-7621 Pecs, Hungary.
[Szuhai, Karoly] Leiden University, Medical Center, Department of Molecular Cell Biology, Einthovenweg 20, 2300RC Leiden, The Netherlands.
[Tornoczky, Tamas] University of Pecs, Department of Pathology, Rakoczi u 2, H-7624 Pecs, Hungary.
RP Semjen, D (reprint author), University of Pecs, Department of Pathology, H-7624 Pecs, Hungary.
EM semjen.david@pte.hu
CR Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM, 2016, The 2016 WHO classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur Urol 70(1):93–105
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Zhang C, Berney DM, Hirsch MS, Cheng L, Ulbright TM, 2013, Evidence supporting the existence of benign teratomas of the postpubertal testis a clinical, histopathologic, and molecular genetic analysis of 25 cases. Am J Surg Pathol 37(6):827–835
Semjen D, Kalman E, Tornoczky T, Szuhai K, 2014, Further evidence of the existence of benign teratomas of the postpubertal testis. Am J Surg Pathol 38(4):580–581
Oosterhuis JW, Stoop JA, Rijlaarsdam MA, Biermann K, Smit VT, Hersmus R, Looijenga LH, 2015, Pediatric germ cell tumors presenting beyond childhood? Andrology 3(1):70–77., DOI 10.1111/andr.305
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Oosterhuis JW, Looijenga LH, 2005, Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 5(3):210–222
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 513
EP 517
DI 10.1007/s12253-016-0120-3
PG 5
ER
PT J
AU Jin, JY
Jeong, WJ
Paik, HJ
Ahn, SH
AF Jin, Ju Young
Jeong, Woo-Jin
Paik, Ho Jin
Ahn, Soon-Hyun
TI Role of Frozen Biopsy in Glottic Premalignant Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glottis premalignant lesion; Glottis cancer; Laser excision; Cordectomy; Frozen biopsy
ID Glottis premalignant lesion; Glottis cancer; Laser excision; Cordectomy; Frozen biopsy
AB Frozen biopsies are frequently used for decision making during surgery. This study aimed to evaluate the efficacy of frozen biopsy for guiding decision making before laser excision of glottic premalignant lesions. One hundred patients with 119 laser excisions were included in this study and reviewed retrospectively. After frozen biopsy, type I or II cordectomy was performed and the frozen result and final pathology of the excisional specimen were compared. The positive predictive value of frozen biopsy when the diagnosis is benign or malignant was relatively high (80.8 and 88.9 %, respectively) but the positive predictive value of a dysplasia or carcinoma in situ result was quite low (18.2 and 16.7 %). Under-diagnosis was frequent for dysplasia or carcinoma in situ (69.7 and 83.3 %). In particular, for lesions with suspicious features, lesions with dysplasia or carcinoma in situ had a much higher rate of under-diagnosis (81.8 and 100 %). Frozen biopsy was not reliable because the overall coincidence rate between final pathology and frozen biopsy was 63 %. Although a frozen biopsy result of a benign or malignant result was reliable, a dysplasia or carcinoma in situ result on frozen biopsy had a high risk of being an under-diagnosis.
C1 [Jin, Ju Young] Seoul National University, College of Medicine, Bundang Hospital, Department of Otorhinolaryngology-Head and Neck Surgery, 173-82 Gumiro, Bundang-gu, 13620 Gyeonggi, South Korea.
[Jeong, Woo-Jin] Seoul National University, College of Medicine, Bundang Hospital, Department of Otorhinolaryngology-Head and Neck Surgery, 173-82 Gumiro, Bundang-gu, 13620 Gyeonggi, South Korea.
[Paik, Ho Jin] Seoul National University, College of Medicine, Bundang Hospital, Department of Pathology, 173-82 Gumiro, Bundang-gu, 13620 Gyeonggi, South Korea.
[Ahn, Soon-Hyun] Seoul National University, College of Medicine, Bundang Hospital, Department of Otorhinolaryngology-Head and Neck Surgery, 173-82 Gumiro, Bundang-gu, 13620 Gyeonggi, South Korea.
RP Ahn, SH (reprint author), Seoul National University, College of Medicine, Bundang Hospital, Department of Otorhinolaryngology-Head and Neck Surgery, 13620 Gyeonggi, South Korea.
EM ahnsh30@snu.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 519
EP 523
DI 10.1007/s12253-016-0143-9
PG 5
ER
PT J
AU Alanazi, M
Pathan, AKA
Shaik, PJ
Alhadheq, A
Khan, Z
Khan, W
Al Naeem, A
Parine, RN
AF Alanazi, Mohammed
Pathan, Ali Khan Akbar
Shaik, P Jilani
Alhadheq, Abdullah
Khan, Zahid
Khan, Wajahatullah
Al Naeem, Abdulrahman
Parine, Reddy Narasimha
TI The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OGG1; Saudi population; Breast cancer; OGG1 Ser326Cys
ID OGG1; Saudi population; Breast cancer; OGG1 Ser326Cys
AB The purpose of this study was to test the association between human 8-oxoguanine glycosylase 1 (hOGG1) gene polymorphisms and susceptibility to breast cancer in Saudi population. We have also aimed to screen the hOGG1 Ser326Cys polymorphism effect on structural and functional properties of the hOGG1 protein using in silico tools. We have analyzed four SNPs of hOGG1 gene among Saudi breast cancer patients along with healthy controls. Genotypes were screened using TaqMan SNP genotype analysis method. Experimental data was analyzed using Chi-square, t test and logistic regression analysis using SPSS software (v.16). In silco analysis was conducted using discovery studio and HOPE program. Genotypic analysis showed that hOGG1 rs1052133 (Ser326Cys) is significantly associated with breast cancer samples in Saudi population, however rs293795 (T >C), rs2072668 (C>G) and rs2075747 (G >A) did not show any association with breast cancer. The hOGG1 SNP rs1052133 (Ser326Cys) minor allele Tshowed a significant association with breast cancer samples (OR = 1.78, χ2 = 7.86, p = 0.02024). In silico structural analysis was carried out to compare the wild type (Ser326) and mutant (Cys326) protein structures. The structural prediction studies revealed that Ser326Cys variant may destabilize the protein structure and it may disturb the hOGG1 function. Taken together this is the first In silico study report to confirm Ser326Cys variant effect on structural and functional properties of hOGG1 gene and Ser326Cys role in breast cancer susceptibility in Saudi population.
C1 [Alanazi, Mohammed] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
[Pathan, Ali Khan Akbar] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
[Shaik, P Jilani] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
[Alhadheq, Abdullah] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
[Khan, Zahid] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
[Khan, Wajahatullah] King Saud bin Abdulaziz University for Health Sciences, College of Science and Health Professions, Basic Sciences Department, 11426 Riyadh, Saudi Arabia.
[Al Naeem, Abdulrahman] King Fahad Medical City, Department of Women’s ImagingRiyadh, Saudi Arabia.
[Parine, Reddy Narasimha] King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
RP Parine, RN (reprint author), King Saud University, College of Science, Genome Research Chair, 11451 Riyadh, Saudi Arabia.
EM reddyparine@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 525
EP 535
DI 10.1007/s12253-016-0146-6
PG 11
ER
PT J
AU Thanmalagan, RR
Naorem, DL
Venkatesan, A
AF Thanmalagan, Rajeswary Raja
Naorem, Devi Leimarembi
Venkatesan, Amouda
TI Expression Data Analysis for the Identification of Potential Biomarker of Pregnancy Associated Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Network analysis; PTM; Pregnancy-associated breast cancer; Association rule mining
ID Network analysis; PTM; Pregnancy-associated breast cancer; Association rule mining
AB Breast cancer affects every 1 of 3000 pregnant women or in the first post-partum year is referred as Pregnancy Associated Breast Cancer (PABC) in mid 30s. Even-though rare disease, classified under hormone receptor negative status which metastasis quickly to other parts by extra cellular matrix degradation. Hence it is important to find an optimal treatment option for a PABC patient. Also additional care should be taken to choose the drug; in order to avoid fetal malformation and post-partum stage side-effects. The adaptation of target based therapy in the clinical practice may help to substitute the mastectomy treatment. Recent studies suggested that certain altered Post Translational Modifications (PTMs) may be an indicative of breast cancer progression; an attempt is made to consider the over represented PTM as a parameter for gene selection. The public dataset of PABC from GEO were examined to select Differentially Expressed Genes (DEG). The corresponding PTMs for DEG were collected and association between them was found using data mining technique. Usually clustering algorithm has been applied for the study of gene expression with drawback of clustering of gene products based on specified features. But association rule mining method overcome this shortcoming and determines the useful and in depth relationships. From the association, genes were selected to study the interactions and pathways. These studies emphasis that the genes KLF12, FEN1 MUC1 and SP110, can be chosen as target, which control cancer development, without any harm to pregnancy as well as fetal developmental process.
C1 [Thanmalagan, Rajeswary Raja] Pondicherry University, Centre for Bioinformatics, 605014 Puducherry, India.
[Naorem, Devi Leimarembi] Pondicherry University, Centre for Bioinformatics, 605014 Puducherry, India.
[Venkatesan, Amouda] Pondicherry University, Centre for Bioinformatics, 605014 Puducherry, India.
RP Venkatesan, A (reprint author), Pondicherry University, Centre for Bioinformatics, 605014 Puducherry, India.
EM amouda@bicpu.edu.in
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 537
EP 544
DI 10.1007/s12253-016-0133-y
PG 8
ER
PT J
AU Salzman, R
Starek, I
Kucerova, L
Skalova, A
AF Salzman, Richard
Starek, Ivo
Kucerova, Ladislava
Skalova, Alena
TI Differing Lymphatic Vessels Density in Salivary Adenoid Cystic Carcinoma and Pleomorphic Adenoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenoid cystic carcinoma; Lymphangiogenesis; Lymphatic vessel; Pleomorphic adenoma; Salivary gland
ID Adenoid cystic carcinoma; Lymphangiogenesis; Lymphatic vessel; Pleomorphic adenoma; Salivary gland
AB Benign and malignant tumours are known to express various factors inducing lymphangiogenesis. Despite their different biological behaviour, salivary pleomorphic adenomas (PA) and adenoid cystic carcinomas (SACC) show similar lymphatic network. Authors compare density of lymphatic network in these tumours. The retrospective study included 20 SACC and 20 PA from salivary tumours. Lymphatic vessel density (LVD) was identified using D2-40 antibody and counted. In SACC, intratumoral, respectively peritumoral, lymphatic vessels were identified in 100 %, respectively 93.8 %, of cases. The intratumoral and peritumoral LVD did not significantly differ from each other. However, they both were higher than normal parenchyma density. In PA, intratumoral LVD, with a single exception, revealed values of 0 and 1. The intratumoral was found to be lower than peritumoral density. The LVD in healthy gland, similar to peritumoral one, was significantly higher than intratumoral values. Direct comparison showed intratumoral and peritumoral LVD in PA to be lower than in SACC. This study comparing LVD in PA and SACC revealed higher values in SACC, outnumbering those in healthy salivary parenchyma and PA. It suggests the capability of this biologically aggressive neoplasm to induce lymphangiogenesis.
C1 [Salzman, Richard] Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc, Department of Otorhinolaryngology, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
[Starek, Ivo] Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc, Department of Otorhinolaryngology, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
[Kucerova, Ladislava] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular Pathology, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
[Skalova, Alena] Charles University, Faculty of Medicine in Plzen, Department of Pathology, Alej svobody 80, 304 60 Pilsen, Czech Republic.
RP Salzman, R (reprint author), Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc, Department of Otorhinolaryngology, 775 20 Olomouc, Czech Republic.
EM richard.salzman@fnol.cz
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 545
EP 550
DI 10.1007/s12253-016-0147-5
PG 6
ER
PT J
AU Enkner, F
Pichlhofer, B
Zaharie, TA
Krunic, M
Holper, MT
Janik, S
Moser, B
Schlangen, K
Neudert, B
Walter, K
Migschitz, B
Mullauer, L
AF Enkner, Franz
Pichlhofer, Bettina
Zaharie, Teodor Alexandru
Krunic, Milica
Holper, Maria Tina
Janik, Stefan
Moser, Bernhard
Schlangen, Karin
Neudert, Barbara
Walter, Karin
Migschitz, Brigitte
Mullauer, Leonhard
TI Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thymoma; Thymic carcinoma; Mutation; miRNA; Immunohistochemistry
ID Thymoma; Thymic carcinoma; Mutation; miRNA; Immunohistochemistry
AB Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9- 3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.
C1 [Enkner, Franz] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Pichlhofer, Bettina] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Zaharie, Teodor Alexandru] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Krunic, Milica] Medical University Vienna, Center for Medical Statistics, Informatics, and Intelligent SystemsVienna, Austria.
[Holper, Maria Tina] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Janik, Stefan] Medical University of Vienna, Department of Thoracic Surgery, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Moser, Bernhard] Medical University of Vienna, Department of Thoracic Surgery, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Schlangen, Karin] Medical University Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Neudert, Barbara] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Walter, Karin] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Migschitz, Brigitte] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
[Mullauer, Leonhard] Medical University of Vienna, Department of Pathology, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
RP Mullauer, L (reprint author), Medical University of Vienna, Department of Pathology, 1090 Vienna, Austria.
EM leonhard.muellauer@meduniwien.ac.at
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 551
EP 564
DI 10.1007/s12253-016-0144-8
PG 14
ER
PT J
AU Zidi, S
Stayoussef, M
Alsaleh, LB
Gazouani, E
Mezlini, A
Ebrahim, HB
Yacoubi-Loueslati, B
Almawi, YW
AF Zidi, Sabrina
Stayoussef, Mouna
Alsaleh, L Bano
Gazouani, Ezzedine
Mezlini, Amel
Ebrahim, H Bashayer
Yacoubi-Loueslati, Besma
Almawi, Y Wassim
TI Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FSHR; Cervical cancer; FIGO stages; Polymorphisms; Haplotypes; Tunisians
ID FSHR; Cervical cancer; FIGO stages; Polymorphisms; Haplotypes; Tunisians
AB For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46–17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01– 0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Stayoussef, Mouna] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Alsaleh, L Bano] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
[Gazouani, Ezzedine] Military Hospital of Tunis, Laboratory of ImmunologyTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Ebrahim, H Bashayer] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
[Yacoubi-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
[Almawi, Y Wassim] Arabian Gulf University, Department of Medical BiochemistryManama, Bahrain.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 565
EP 572
DI 10.1007/s12253-016-0152-8
PG 8
ER
PT J
AU Zhang, Y
Zhou, J
Sun, M
Sun, G
Cao, Y
Zhang, H
Tian, R
Zhou, L
Duan, L
Chen, X
Lun, L
AF Zhang, Yunyuan
Zhou, Jun
Sun, Meiling
Sun, Guirong
Cao, Yongxian
Zhang, Haiping
Tian, Runhua
Zhou, Lan
Duan, Liang
Chen, Xian
Lun, Limin
TI Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-9; Cancer; Prognosis; Meta-analysis
ID miR-9; Cancer; Prognosis; Meta-analysis
AB Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56–3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33–3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.
C1 [Zhang, Yunyuan] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Zhou, Jun] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Sun, Meiling] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Sun, Guirong] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Cao, Yongxian] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Zhang, Haiping] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Tian, Runhua] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Zhou, Lan] Chongqing Medical University, College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics Designated by Chinese Ministry of Education, 400016 Chongqing, China.
[Duan, Liang] the Second Hospital Affiliated to Chongqing Medical University, Department of Laboratory Medicine, 400010 Chongqing, China.
[Chen, Xian] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
[Lun, Limin] The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
RP Chen, X (reprint author), The Affiliated Hospital of Qingdao University, Department of Clinical Laboratory, 266003 Qingdao, China.
EM cxkakicoco2014@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 573
EP 582
DI 10.1007/s12253-016-0148-4
PG 10
ER
PT J
AU Molnar, E
Schultz, M
Schmidt-Schultz, HTy
Marcsik, A
Buczko, K
Zadori, P
Biro, G
Bernert, Zs
Baumhoer, D
Hajdu, T
AF Molnar, Erika
Schultz, Michael
Schmidt-Schultz, H Tyede
Marcsik, Antonia
Buczko, Krisztina
Zadori, Peter
Biro, Gergely
Bernert, Zsolt
Baumhoer, Daniel
Hajdu, Tamas
TI Rare Case of an Ancient Craniofacial Osteosarcoma with Probable Surgical Intervention
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Craniofacial osteosarcoma; Paleopathology; Incomplete trephination
ID Craniofacial osteosarcoma; Paleopathology; Incomplete trephination
AB Osteosarcoma is the most common primary malignant bone tumor both today and in antiquity. Nevertheless, it is a comparatively rare tumor. This paper describes a case of a highly aggressive craniofacial lesion from the 11th–12th centuries AD, most likely representing osteosarcoma. During the paleopathological study, macroscopic, endoscopic, radiological, scanning-electron and light microscopic investigations were performed. The skull of the approximately 40–50 yearold female revealed several pathological findings. The most impressive macroscopic feature was an extensively spiculated periosteal reaction ("sunburst" pattern) in combination with a massive bone destruction most likely derived from a highly aggressive tumor originating in the ethmoidal area of the medial wall of the orbit. The central parts of the lesion showed excessive new and most probably neoplastic bone formation indicating an underlying high-grade osteosarcoma. The light microscopic examination revealed three different levels of bony structures representing different qualities of bone tissues. Besides the mass lesion, signs of a healed multiple incomplete trephination of the left parietal bone was observed. This case represents a unique example in which the concomitance of a tumor and an incomplete trephination could be observed from the skeletal remains of an ancient individual. The case opens new considerations as to whether surgical interventions, such as incomplete trephination, might have been used already in the Middle Ages as a therapeutic approach.
C1 [Molnar, Erika] University of Szeged, Department of Anatomy, Kozep fasor 52, H-6726 Szeged, Hungary.
[Schultz, Michael] University Medical School Gottingen, Department of Anatomy, Kreuzbergring 36, D-37075 Gottingen, Germany.
[Schmidt-Schultz, H Tyede] University Medical School Gottingen, Department of Anatomy, Kreuzbergring 36, D-37075 Gottingen, Germany.
[Marcsik, Antonia] University of Szeged, Department of Anatomy, Kozep fasor 52, H-6726 Szeged, Hungary.
[Buczko, Krisztina] Hungarian Natural History Museum, Department of Botany, Konyves Kalman korut 40, H-1097 Budapest, Hungary.
[Zadori, Peter] Kaposi Mor Teaching Hospital, Guba Sandor utca 40, H-7400 Kaposvar, Hungary.
[Biro, Gergely] Kaposi Mor Teaching Hospital, Guba Sandor utca 40, H-7400 Kaposvar, Hungary.
[Bernert, Zsolt] Hungarian Natural History Museum, Department of Anthropology, Ludovika ter 2, H-1083 Budapest, Hungary.
[Baumhoer, Daniel] University Hospital Basel, Institute of Pathology, Bone Tumor Reference Center, Schonbeinstrasse 40, D-4031 Basel, Switzerland.
[Hajdu, Tamas] Hungarian Natural History Museum, Department of Anthropology, Ludovika ter 2, H-1083 Budapest, Hungary.
RP Molnar, E (reprint author), University of Szeged, Department of Anatomy, H-6726 Szeged, Hungary.
EM balinte@bio.u-szeged.hu
CR David AR, Zimmerman MR, 2010, Cancer: an old disease, a new disease or something in between? Nat Rev Cancer 10:728–733
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SchultzM, Parzinger H, Posdnjakov DV, Chikisheva TA, Schmidt- Schultz TH, 2007, Oldest known case of metastasizing prostate carcinoma diagnosed in the skeleton of a 2,700-year-old Scythian king from Arzhan, Siberia, Russia). Int J Cancer 121:2591–2595
Ortner DJ, 2011)What skeletons tell us. The story of human paleopathology. Virchows Arch 459(3):247–254., DOI 10.1007/s00428- 011-1122-x
Halperin EC, 2004, Paleo-oncology: the role of ancient remains in the study of cancer. Perspect Biol Med 47:1–14
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 583
EP 587
DI 10.1007/s12253-016-0153-7
PG 5
ER
PT J
AU Patai, V
Bartak, KB
Peterfia, B
Micsik, T
Horvath, R
Sumanszki, Cs
Peter, Z
Patai,
Valcz, G
Kalmar, A
Toth, K
Krenacs, T
Tulassay, Zs
Molnar, B
AF Patai, V Arpad
Bartak, Kinga Barbara
Peterfia, Balint
Micsik, Tamas
Horvath, Reka
Sumanszki, Csaba
Peter, Zoltan
Patai, Arpad
Valcz, Gabor
Kalmar, Alexandra
Toth, Kinga
Krenacs, Tibor
Tulassay, Zsolt
Molnar, Bela
TI Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarker; DNA methylation; Mutation; Serrated polyp; Sessile serrated adenoma; Traditional serrated adenoma
ID Biomarker; DNA methylation; Mutation; Serrated polyp; Sessile serrated adenoma; Traditional serrated adenoma
AB Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n = 4) and healthy controls (n = 5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.
C1 [Patai, V Arpad] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Bartak, Kinga Barbara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Peterfia, Balint] Hungarian Academy of Sciences, Molecular Medicine Research Group, Roosevelt ter 9, 1051 Budapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Horvath, Reka] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Sumanszki, Csaba] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Peter, Zoltan] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Patai, Arpad] Markusovszky Hospital, Department of Medicine and Gastroenterology, Markusovszky Lajos utca 5, 9700 Szombathely, Hungary.
[Valcz, Gabor] Hungarian Academy of Sciences, Molecular Medicine Research Group, Roosevelt ter 9, 1051 Budapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
RP Patai, V (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM arpad.patai@gmail.com
CR East JE, Vieth M, Rex DK, 2015, Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance. Gut 64:991–1000
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Sipos F,Muzes G, Patai AV, Furi I, Peterfia B, Hollosi P, Molnar B, Tulassay Z, 2013, Genome-wide screening for understanding the role of DNA methylation in colorectal cancer. Epigenomics 5:569– 581
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 589
EP 594
DI 10.1007/s12253-016-0154-6
PG 6
ER
PT J
AU Arzt, L
Halbwedl, I
Gogg-Kamerer, M
Popper, HH
AF Arzt, Lisa
Halbwedl, Iris
Gogg-Kamerer, Margit
Popper, H Helmut
TI Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Malignant pleural mesothelioma; STAT signaling; miRNA; Apoptosis
ID Malignant pleural mesothelioma; STAT signaling; miRNA; Apoptosis
AB Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knockeddown using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.
C1 [Arzt, Lisa] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Halbwedl, Iris] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Gogg-Kamerer, Margit] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Popper, H Helmut] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
RP Arzt, L (reprint author), Medical University of Graz, Department of Pathology, A-8036 Graz, Austria.
EM lisa.arzt@medunigraz.at
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 595
EP 605
DI 10.1007/s12253-016-0157-3
PG 11
ER
PT J
AU Szczyrek, M
Mlak, R
Krawczyk, P
Wojas-Krawczyk, K
Powrozek, T
Szudy-Szczyrek, A
Zwolak, A
Daniluk, J
Milanowski, J
AF Szczyrek, Michal
Mlak, Radoslaw
Krawczyk, Pawel
Wojas-Krawczyk, Kamila
Powrozek, Tomasz
Szudy-Szczyrek, Aneta
Zwolak, Agnieszka
Daniluk, Jadwiga
Milanowski, Janusz
TI Polymorphisms of Genes Encoding Multidrug Resistance Proteins as a Predictive Factor for Second-Line Docetaxel Therapy in Advanced Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NSCLC; Docetaxel; TUBB3; ABCC2; MDR1
ID NSCLC; Docetaxel; TUBB3; ABCC2; MDR1
AB Multidrug resistance (MDR) remains a substantial problem in chemotherapy. The purpose of the study was to investigate potential factors, including MDR genes polymorphisms, that could be used in qualification for second-line docetaxel therapy in non-small cell lung cancer (NSCLC) patients after failure of platinum based chemotherapy. Study group comprised of 58 Caucasian subjects. Evaluation of Single Nucleotide Polymorphisms (SNPs) of ABCC2/MRP2 and ABCB1/MDR1 genes was performed using the High Resolution Melting (HRM) technique. TUBB3 gene expression was evaluated on RNA isolated from tumor tissue. Results with p value of <0.05 were considered significant. Factors associated with reduced risk of disease progression included good performance status (PS), long period between diagnosis and docetaxel treatment, and smoking for <10 packyears. Disease control occurred more often in patients with G/G genotype of the ABCC2/MRP2 gene. Median overall survival was 4.25 months. Factors such as: good PS, disease control after docetaxel, long period from diagnosis to docetaxel, lack of significant weight loss, and third-line treatment were associated with prolongation of patients survival. Overall survival probability was significantly lower in patients with significant weight loss, poor PS, lack of disease control after docetaxel, and without third-line treatment. Factors that characterized the highest risk of survival shortening were: inability to apply third-line treatment, lack of best response to first-line therapy, poor PS, and C/G or G/G genotypes of ABCC2/MRP2 gene. We concluded that assessed factors had mainly prognostic and not predictive value. Finding reliable molecular predictors for second line docetaxel therapy requires further clinical trials.
C1 [Szczyrek, Michal] Medical University of Lublin, Department of Pneumonology, Oncology and AllergologyLublin, Poland.
[Mlak, Radoslaw] Medical University of Lublin, Department of Human PhysiologyLublin, Poland.
[Krawczyk, Pawel] Medical University of Lublin, Department of Pneumonology, Oncology and AllergologyLublin, Poland.
[Wojas-Krawczyk, Kamila] Medical University of Lublin, Department of Pneumonology, Oncology and AllergologyLublin, Poland.
[Powrozek, Tomasz] Medical University of Lublin, Department of Pneumonology, Oncology and AllergologyLublin, Poland.
[Szudy-Szczyrek, Aneta] Medical University of Lublin, Chair and Department of Haematooncology and Bone Marrow TransplantationLublin, Poland.
[Zwolak, Agnieszka] Medical University of Lublin, Chair of Internal Medicine and Department of Internal Medicine in NursingLublin, Poland.
[Daniluk, Jadwiga] Medical University of Lublin, Chair of Internal Medicine and Department of Internal Medicine in NursingLublin, Poland.
[Milanowski, Janusz] Medical University of Lublin, Department of Pneumonology, Oncology and AllergologyLublin, Poland.
RP Szczyrek, M (reprint author), Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Lublin, Poland.
EM mszczyrek@yahoo.co.uk
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 607
EP 614
DI 10.1007/s12253-016-0156-4
PG 8
ER
PT J
AU Hu, W
Li, X
Li, Q
Tan, Y
Xu, B
Xie, Q
Deng, X
Lu, B
Jiang, J
Wu, Ch
AF Hu, Wenwei
Li, Xiaodong
Li, Qing
Tan, Yan
Xu, Bin
Xie, Quanqin
Deng, Xu
Lu, Binfeng
Jiang, Jingting
Wu, Changping
TI Interleukin-33 Expression does not Correlate with Survival of Gastric Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Interleukin-33; Gastric cancer; Clinical characteristics; Survival
ID Interleukin-33; Gastric cancer; Clinical characteristics; Survival
AB The aim of the study was to investigate IL-33 expression in gastric cancer (GC) and its association with the clinical characteristics and the prognosis. IL- 33 protein in tumor and corresponding adjacent tissues were detected by immunohistochemistry in 179 GC patients and clinical features plus prognostic value were analyzed via Pearson’s chi-square test and Kaplan– Meier test in Cox proportional hazards model, respectively. IL-33 protein levels were significantly lower in tumor tissues than adjacent tissues (29.05% vs. 78.77%, χ2 = 89.05, P < 0.001). The positive rate of IL-33 in the ulcerative type group was the lowest among all groups (P < 0.05). IL-33 levels were correlated with age (P = 0.025) and invasion depth (P = 0.030) while not significantly associated with the overall survival of GC patients. IL-33 expression is associated with age and invasive depth of GC patients but not an independent risk factor of prognosis.
C1 [Hu, Wenwei] The Third Affiliated Hospital of Soochow University, Department of OncologyChangzhou, Jiangsu Province, China.
[Li, Xiaodong] The Third Affiliated Hospital of Soochow University, Department of OncologyChangzhou, Jiangsu Province, China.
[Li, Qing] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, Jiangsu Province, China.
[Tan, Yan] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, Jiangsu Province, China.
[Xu, Bin] The Third Affiliated Hospital of Soochow University, Department of Tumor Biological TreatmentChangzhou, Jiangsu Province, China.
[Xie, Quanqin] The Third Affiliated Hospital of Soochow University, Department of Tumor Biological TreatmentChangzhou, Jiangsu Province, China.
[Deng, Xu] The Third Affiliated Hospital of Soochow University, Department of Tumor Biological TreatmentChangzhou, Jiangsu Province, China.
[Lu, Binfeng] University of Pittsburgh, School of Medicine, Department of ImmunologyPittsburgh, PA, USA.
[Jiang, Jingting] The Third Affiliated Hospital of Soochow University, Department of Tumor Biological TreatmentChangzhou, Jiangsu Province, China.
[Wu, Changping] The Third Affiliated Hospital of Soochow University, Department of OncologyChangzhou, Jiangsu Province, China.
RP Wu, Ch (reprint author), The Third Affiliated Hospital of Soochow University, Department of Oncology, Changzhou, China.
EM wcpjjt@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 615
EP 619
DI 10.1007/s12253-016-0167-1
PG 5
ER
PT J
AU Soleimani, Z
Kheirkhah, D
Sharif, RM
Sharif, A
Karimian, M
Aftabi, Y
AF Soleimani, Zahra
Kheirkhah, Davood
Sharif, Reza Mohammad
Sharif, Alireza
Karimian, Mohammad
Aftabi, Younes
TI Association of CCND1 Gene c.870G>A Polymorphism with Breast Cancer Risk: A Case-Control Study and a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; CCND1 gene; Genetic polymorphism; c.870G>A; Meta-analysis
ID Breast cancer; CCND1 gene; Genetic polymorphism; c.870G>A; Meta-analysis
AB Cyclin D1 (CCND1) plays an essential role in regulating the progress of the cell cycle from G1 to S phase. There is a common c.870G>A polymorphism in the CCND1 gene. The aim of this study was to investigate the association of CCND1 gene c.870G>A polymorphism with breast cancer risk in a case-control study, which followed by a meta-analysis and an in silico analysis. Three hundred and thirty-five subjects composed of 174 women with breast cancer and 161 healthy controls were included in the case-control study. CCND1 gene c.870G>A genotyping was performed by PCR-RFLP. Meta-analysis was done for 14 studies composed of 7281 cases and 6820 controls. Some bioinformatics tools were applied to investigate the effects of c.870G>A on the mRNA splicing and structure. Our data obtained from casecontrol study revealed that GA genotype (OR: 1.89, 95%CI: 1.12–3.17, p = 0.017), AA genotype (OR: 1.95, 95%CI: 1.08– 3.53, p = 0.027), and A allele (OR: 1.44, 95%CI: 1.06–1.95, p = 0.019) were significantly associated with breast cancer risk. The results of meta-analysis showed a significant association between CCND1 c.870G>A polymorphism and breast cancer risk, especially in Caucasian population. In silico analysis revealed that c.870G>A transition affect CCND1 mRNA splicing and secondary structure.
C1 [Soleimani, Zahra] Kashan University of Medical Sciences, Infectious Diseases Research CenterKashan, Iran.
[Kheirkhah, Davood] Kashan University of Medical Sciences, Trauma Research CenterKashan, Iran.
[Sharif, Reza Mohammad] Kashan University of Medical Sciences, Autoimmune Diseases Research CenterKashan, Iran.
[Sharif, Alireza] Kashan University of Medical Sciences, Infectious Diseases Research CenterKashan, Iran.
[Karimian, Mohammad] Kashan University of Medical Sciences, Gametogenesis Research CenterKashan, Iran.
[Aftabi, Younes] Tabriz University of Medical Sciences, Drug Applied Research CenterTabriz, Iran.
RP Kheirkhah, D (reprint author), Kashan University of Medical Sciences, Trauma Research Center, Kashan, Iran.
EM kheirkhahdavood@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 621
EP 631
DI 10.1007/s12253-016-0165-3
PG 11
ER
PT J
AU Butz, H
Nemeth, K
Czenke, D
Liko, I
Czirjak, S
Zivkovic, V
Baghy, K
Korbonits, M
Kovalszky, I
Igaz, P
Racz, K
Patocs, A
AF Butz, Henriett
Nemeth, Kinga
Czenke, Dora
Liko, Istvan
Czirjak, Sandor
Zivkovic, Vladimir
Baghy, Kornelia
Korbonits, Marta
Kovalszky, Ilona
Igaz, Peter
Racz, Karoly
Patocs, Attila
TI Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pituitary adenoma; Cell cycle; G2/M transition; CDC25A; miRNA
ID Pituitary adenoma; Cell cycle; G2/M transition; CDC25A; miRNA
AB Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/Mtransition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25Awere validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes’ expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially regulated by miRNAs.
C1 [Butz, Henriett] Hungarian Academy of Sciences, Molecular Medicine Research Group, 46 Szentkiralyi str, H-1088 Budapest, Hungary.
[Nemeth, Kinga] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Czenke, Dora] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Liko, Istvan] Hungarian Academy of SciencesBudapest, Hungary.
[Czirjak, Sandor] National Institute of NeurosurgeryBudapest, Hungary.
[Zivkovic, Vladimir] University of Belgrade, School of Medicine, Institute of Forensic MedicineBelgrade, Serbia.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Korbonits, Marta] Queen Mary University of London, Barts and the London School of Medicine, Department of EndocrinologyLondon, UK.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Igaz, Peter] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Racz, Karoly] Hungarian Academy of Sciences, Molecular Medicine Research Group, 46 Szentkiralyi str, H-1088 Budapest, Hungary.
[Patocs, Attila] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
RP Butz, H (reprint author), Hungarian Academy of Sciences, Molecular Medicine Research Group, H-1088 Budapest, Hungary.
EM butz.henriett@med.semmelweis-univ.hu
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D'Angelo D, Palmieri D, Mussnich P, Roche M, Wierinckx A, Raverot G, Fedele M, Croce CM, Trouillas J, Fusco A, 2012, Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1. J Clin Endocrinol Metab 97:E1128–E1138
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 633
EP 641
DI 10.1007/s12253-016-0163-5
PG 9
ER
PT J
AU Niedworok, Ch
Tschirdewahn, S
Reis, H
Lehmann, N
Szucs, M
Nyirady, P
Romics, I
Rubben, H
Szarvas, T
AF Niedworok, Christian
Tschirdewahn, Stephan
Reis, Henning
Lehmann, Nils
Szucs, Miklos
Nyirady, Peter
Romics, Imre
Rubben, Herbert
Szarvas, Tibor
TI Serum Chromogranin A as a Complementary Marker for the Prediction of Prostate Cancer-Specific Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chromogranin A; CGA; Prostate cancer; Prognosis; KRYPTOR
ID Chromogranin A; CGA; Prostate cancer; Prognosis; KRYPTOR
AB Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p < 0.001 and; 41 vs. 22 ng/ml; p = 0.002 respectively). In accordance, high CGA levels were correlated with poor DSS. In clinically localized cases, CGA levels alone were not prognostic, but its dichotomized combinations with PSA or MMP7 were independently associated with DSS (HR: 4.88, 95% CI: 1.35–17.71, p = 0.016, HR: 7.46, 1.65–33.63, p = 0.009, respectively). Elevated serum CGA levels in progressed PCA and its prognostic value suggest a potential for CGA in disease monitoring. Our results revealed no independent prognostic value for CGA as a single serum marker in clinically localized cases. However, when combining with PSA or MMP7, CGA may improve both marker’s performance in distinguishing between clinically significant and indolent PCAs.
C1 [Niedworok, Christian] University of Duisburg-Essen, Department of UrologyEssen, Germany.
[Tschirdewahn, Stephan] University of Duisburg-Essen, Department of UrologyEssen, Germany.
[Reis, Henning] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Lehmann, Nils] University of Duisburg-Essen, University Hospital of Essen, Institute of Medical Informatics, Biometry and EpidemiologyEssen, Germany.
[Szucs, Miklos] Semmelweis University, Department of Urology, Ulloi ut 78/b, 1082 Budapest, Hungary.
[Nyirady, Peter] Semmelweis University, Department of Urology, Ulloi ut 78/b, 1082 Budapest, Hungary.
[Romics, Imre] Semmelweis University, Department of Urology, Ulloi ut 78/b, 1082 Budapest, Hungary.
[Rubben, Herbert] University of Duisburg-Essen, Department of UrologyEssen, Germany.
[Szarvas, Tibor] University of Duisburg-Essen, Department of UrologyEssen, Germany.
RP Szarvas, T (reprint author), University of Duisburg-Essen, Department of Urology, Essen, Germany.
EM sztibusz@gmail.com
CR Jemal A, Siegel R, Xu J,Ward E, 2011, Cancer statistics, 2010. CA Cancer J Clin 61:133–134
Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Maattanen L, Lilja H, Denis LJ, Recker F, Paez A, Bangma CH, Carlsson S, Puliti D, Villers A, Rebillard X, Hakama M, Stenman UH, Kujala P, Taari K, Aus G, Huber A, van der Kwast TH, van Schaik RH, de Koning HJ, Moss SM, Auvinen A, 2014, ERSPC investigators. Screening and prostate cancer mortality: results of the European randomised study of screening for prostate cancer, ERSPC, at 13 years of follow-up. Lancet 384:2027–2035
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Niedworok C, Vom Dorp F, Tschirdewahn S, Rubben H, Reis H, Szucs M, Szarvas T, 2016, Validation of the diagnostic and prognostic relevance of serumMMP7 levels in renal cell cancer by using a novel automated fluorescent immunoassay method. Int Urol Nephrol 48:355–361
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Harrell FE Jr, 2001, Regression modelling strategies with applications to linear models, logistic regression, and survival analysis. Springer, New York
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 643
EP 650
DI 10.1007/s12253-016-0171-5
PG 8
ER
PT J
AU Peng, W
Wang, Z
Fan, H
AF Peng, Wei
Wang, Zhuo
Fan, Hong
TI LncRNA NEAT1 Impacts Cell Proliferation and Apoptosis of Colorectal Cancer via Regulation of Akt Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Long noncoding RNA; NEAT1; Biomarker
ID Colorectal cancer; Long noncoding RNA; NEAT1; Biomarker
AB Long noncoding RNA (lncRNA) have been reported to modulate oncogenesis and be used to be target for tumor. The role of lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1, Gene ID: 283131) in colorectal cancer (CRC) keeps unknown. This work was to investigate the pattern of lncRNA NEAT1 (NEAT1) expression in CRC and its functional value and biological significance. NEAT1 expression was analyzed in 56 cancer tissues and cell lines in CRC cases. Results showed that NEAT1 was significantly overexpressed in CRC cells and tissues. Clinicpathologic detection verified that high NEAT1 expression associated with bulk in CRC. The serum contents of NEAT1 were observably elevated comparing with healthy cases (P < 0.05). The levels of NEAT1 were elevated in distinguishing CRC from normal (ROCAUC = 0.9471; P < 0.01). Moreover, Kaplan–Meier analysis found that NEAT1 elevation led to adverse survival (P < 0.05). Further experiments illustrated that of NEAT1 knockdown signally inhibited growth and facilitated apoptosis. Importantly, we confirmed that Akt signaling pathway was inactivated after loss of NEAT1 in CRC. Taken together, this work support the first evidence that NEAT1 can be used to be a promising biomarker and target for novel treatment for human CRC.
C1 [Peng, Wei] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, No. 42 Baiziting Road, 210009 Nanjing, China.
[Wang, Zhuo] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Laboratory of Cancer Research, No. 42 Baiziting Road, 210009 Nanjing, China.
[Fan, Hong] First People’s Hospital of Yunnan Province, Department of Gastroenterology, No. 175 Jinbi Road, 650032 Kunming, China.
RP Peng, W (reprint author), Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, 210009 Nanjing, China.
EM wpeng01@hotmail.com
CR Weitz J, KochM, Debus J, Hohler T, Galle PR, BuchlerMW(2005, Colorectal cancer. Lancet 365(9454):153–165
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Wilusz JE, Sunwoo H, Spector DL, 2009, Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494– 1504
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PengW,Wu G, Fan H,Wu J, Feng J, 2015, Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer. Tumour biology: the journal of the international society for. Oncodevelopmental Biology and Medicine 36: 6751–6758
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Wang P, Wu T, Zhou H, Jin Q, He G, Yu H et al, 2016, Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway. Journal of experimental & clinical cancer research: CR 35:22
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Peng W, Wu JZ, Feng JF, 2016, Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma. Biomedicine & Pharmacotherapy 79:188–193
Altomare DA, Testa JR, 2005, Perturbations of the AKT signaling pathway in human cancer. Oncogene 24:7455–7464
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 651
EP 656
DI 10.1007/s12253-016-0172-4
PG 6
ER
PT J
AU Zhu, Y
Liu, M
Yun, X
Wang, D
Bai, Y
Zhang, G
Ji, B
Jing, Ch
AF Zhu, Yusen
Liu, Min
Yun, Xiaojing
Wang, Dongmei
Bai, Yuhuan
Zhang, Guizhi
Ji, Bei
Jing, Changchun
TI Meta-Analysis for the Therapeutic Effect of Neoadjuvant Therapy in Resectable Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; Neoadjuvant chemoradiotherapy; Neoadjuvant chemotherapy; Neoadjuvant radiotherapy; Meta-analysis
ID Esophageal cancer; Neoadjuvant chemoradiotherapy; Neoadjuvant chemotherapy; Neoadjuvant radiotherapy; Meta-analysis
AB We aimed to review the therapeutic effects of neoadjuvant chemoradiotherapy (NCRT), chemotherapy (NCT), and radiotherapy (NRT) on patients with resectable Esophageal cancer (EsC) by comparison with surgery alone (SA). PubMed, EMBASE and Cochrane were searched for eligible studies published up to March 2015. Cochrane reviews were used for quality assessment. Eight primary outcomes were analyzed. Risk ratios (RRs)/ hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the random- or fixed- effects model. Heterogeneity was assessed using the Chi-square-based Q statistic and the I2test. Publication bias was examined by the Begg’s funnel plot. Totally 24 articles including 4718 EsC cases were eligible for this meta-analysis. The quality of the literatures was relatively high. Significant difference was found in five-year survival rate (RR = 1.45, 95% CI: 1.17–1.79, P < 0.01) between patients treated with NCT and SA, while the eight enrolled primary outcomes were all statistically different between NCRT and SA, and significant difference was identified in three-year survival between NCRT and NCT (RR = 1.35, 95% CI: 1.14–1.60, P < 0.01). No obvious publication bias was observed. NCRT and NCT provide an obvious benefit for EsC treatment over SA, and NCRT possesses a clear advantage compared with NCT.
C1 [Zhu, Yusen] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Liu, Min] The Second People’s Hospital of Liaocheng, Department of Emergency, 252600 Linqing, Shandong, China.
[Yun, Xiaojing] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Wang, Dongmei] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Bai, Yuhuan] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Zhang, Guizhi] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Ji, Bei] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
[Jing, Changchun] The Second People’s Hospital of Liaocheng, Department of Gastroenterology, 252600 Linqing, Shandong, China.
RP Liu, M (reprint author), The Second People’s Hospital of Liaocheng, Department of Emergency, 252600 Linqing, China.
EM minliu01@126.com
CR Pennathur A, Gibson MK, Jobe BA, Luketich JD, 2013, Oesophageal carcinoma. Lancet 381:400–412
Vallbohmer D, Brabender J, Grimminger P, Schroder W, Holscher AH, 2011, Predicting response to neoadjuvant therapy in esophageal cancer. Expert Rev Anticancer Ther 11:1449–1455
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ, 2009, Cancer statistics, 2009. CA Cancer J Clin 59:225–249
Shahbaz SarwarCM, Luketich JD, Landreneau RJ, AbbasG, 2010, Esophageal cancer: an update. Int J Surg 8:417–422
Krasna MJ, 2010, Multimodality therapy for esophageal cancer. Oncology, Williston Park, 24:1134–1138
D'journo XB, Thomas PA, 2014, Current management of esophageal cancer. J Thorac Dis 6(Suppl 2):S253–S264
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Shah RD, Cassano AD, Neifeld JP, 2014, Neoadjuvant therapy for esophageal cancer. World J Gastrointest Oncol 6:403–406
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Ychou M, Boige V, Pignon J-P et al, 2011, Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 657
EP 663
DI 10.1007/s12253-016-0164-4
PG 7
ER
PT J
AU Stefanko, E
Rybka, J
Jazwiec, B
Haus, O
Stapor, S
Kuliczkowski, K
Wrobel, T
AF Stefanko, Ewa
Rybka, Justyna
Jazwiec, Bozena
Haus, Olga
Stapor, Sylwia
Kuliczkowski, Kazimierz
Wrobel, Tomasz
TI Significance of OCT1 Expression in Acute Myeloid Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute myeloid leukemia; OCT1; Resistance to chemotherapy
ID Acute myeloid leukemia; OCT1; Resistance to chemotherapy
AB Organic cation transporter 1 (OCT1) is one of the membrane proteins in the large solute carrier (SLC) family. It participates in the transport of organic cations, i.e. nutrients, neurotransmitters, metabolites or drugs in an electrogenic manner and translocate various cationic cytostatics. Knowledge concerning the expression of drug transporters in tumor cells may help to develop cytotoxic agents that are targeted to specific tumors. OCT1 expression and its relationship to the proliferation of cancer cells, development of metastases and resistance to chemotherapy has been observed in solid tumors. There is no data concerning the significance of OCT1 expression in the clinical course and treatment results in acute myeloid leukemia (AML). The objective of the study was firstly to evaluate OCT1 mRNA expression in patients with newly diagnosed de novo AML, and secondly to compare the obtained results to the healthy control group as well as analyze them according to leukemia subtypes, CD34 expression, cytogenetic and molecular factors and treatment results. 101 patients with AML, excluding the subtype classified as M3 by French-American-British (FAB) criteria, were analyzed. The control group consisted of 26 healthy individuals. The evaluated material was bone marrow (BM). Real-time quantitative polymerase chain reaction (RQ-PCR) was used in the study as a method of evaluating OCT1 mRNA expression. The study showed a statistically significant lower expression of OCT1 mRNA in patients with AML in comparison to the control group. The level of OCT1 mRNA expression was lowest for CD34+ leukemia. No significant correlation between OCT1 mRNA expression and cytogenetic and molecular factors was observed. A significant influence of OCT1 mRNA expression on the clinical outcome of the disease was observed: patients with lower expression had higher chances of achieving complete remission (CR) and longer overall survival (OS).
C1 [Stefanko, Ewa] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Rybka, Justyna] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Jazwiec, Bozena] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Haus, Olga] Collegium Medicum Nicolaus Copernicus University, Department of Clinical GeneticsBydgoszcz, Poland.
[Stapor, Sylwia] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Kuliczkowski, Kazimierz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
[Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow TransplantationWroclaw, Poland.
RP Stefanko, E (reprint author), Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw, Poland.
EM ewastefanko@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 665
EP 671
DI 10.1007/s12253-016-0161-7
PG 7
ER
PT J
AU Khan, AS
Zeng, Z
Shia, J
Paty, BP
AF Khan, A Sajid
Zeng, Zhaoshi
Shia, Jinru
Paty, B Philip
TI EGFR Gene Amplification and KRAS Mutation Predict Response to Combination Targeted Therapy in Metastatic Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Cetuximab; Bevacizumab; Metastasis; EGFR; KRAS
ID Colorectal cancer; Cetuximab; Bevacizumab; Metastasis; EGFR; KRAS
AB Genetic variability in KRAS and EGFR predicts response to cetuximab in irinotecan refractory colorectal cancer. Whether these markers or others remain predictive in combination biologic therapies including bevacizumab is unknown. We identified predictive biomarkers from patients with irinotecan refractory metastatic colorectal cancer treated with cetuximab plus bevacizumab. Patients who received cetuximab plus bevacizumab for irinotecan refractory colorectal cancer in either of two Phase II trials conducted were identified. Tumor tissue was available for 33 patients. Genomic DNA was extracted and used for mutational analysis of KRAS, BRAF, and p53 genes. Fluorescence in situ hybridization was performed to assess EGFR copy number. The status of single genes and various combinations were tested for association with response. Seven of 33 patients responded to treatment. KRAS mutations were found in 14/33 cases, and 0 responded to treatment (p = 0.01). EGFR gene amplification was seen in 3/33 of tumors and in every case was associated with response to treatment (p < 0.001). TP53 and BRAF mutations were found in 18/33 and 0/33 tumors, respectively, and there were no associations with response to either gene. EGFR gene amplification and KRAS mutations are predictive markers for patients receiving combination biologic therapy of cetuximab plus bevacizumab for metastatic colorectal cancer. One marker or the other is present in the tumor of half of all patients allowing treatment response to be predicted with a high degree of certainty. The role for molecular markers in combination biologic therapy seems promising.
C1 [Khan, A Sajid] Yale University School of Medicine, Department of Surgery, Section of Surgical Oncology, 310 Cedar Street, FMB 130, 06520 New Haven, CT, USA.
[Zeng, Zhaoshi] Memorial Sloan-Kettering Cancer Center, Colorectal Service, Department of SurgeryNew York, NY, USA.
[Shia, Jinru] Memorial Sloan-Kettering Cancer Center, Colorectal Service, Department of PathologyNew York, NY, USA.
[Paty, B Philip] Memorial Sloan-Kettering Cancer Center, Colorectal Service, Department of SurgeryNew York, NY, USA.
RP Khan, AS (reprint author), Yale University School of Medicine, Department of Surgery, Section of Surgical Oncology, 06520 New Haven, USA.
EM sajid.khan@yale.edu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 673
EP 677
DI 10.1007/s12253-016-0166-2
PG 5
ER
PT J
AU Sitarek, P
Skala, E
Toma, M
Wielanek, M
Szemraj, J
Skorski, T
Bialas, JA
Sakowicz, T
Kowalczyk, T
Radek, M
Wysokinska, H
Sliwinski, T
AF Sitarek, Przemyslaw
Skala, Ewa
Toma, Monika
Wielanek, Marzena
Szemraj, Janusz
Skorski, Tomasz
Bialas, J Adam
Sakowicz, Tomasz
Kowalczyk, Tomasz
Radek, Maciej
Wysokinska, Halina
Sliwinski, Tomasz
TI Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apoptosis; Cell cycle; Gene expression; Transformed roots of Leonurus sibiricus; Mitochondrial membrane potential; Reactive oxygen species
ID Apoptosis; Cell cycle; Gene expression; Transformed roots of Leonurus sibiricus; Mitochondrial membrane potential; Reactive oxygen species
AB This study determines the influence of transformed root (TR) extract of Leonurus sibiricus L. on various grades (IIII) of human glioma cells derived from patients. This plant occurs in southern Asia and Siberia and is widely used as a medicinal plant with various biological activities. Chromatographic profile of TR extract have revealed the presence of various polyphenolic compounds (4-hydroxybenzoic acid, gentisic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α- resorcylic acid). We found TR root extract to have antiproliferative activity on glioma cells after 24 h of treatment. TR root extract induces apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, enhanced S and G2/M phases of the cell cycle, and altered mRNA levels of Bax, Bcl-2, p53, Cas-3, Cas-8 and Cas- 9 factors involved in apoptosis. This work for the first time demonstrate that TR extract from L. sibiricus root has the potential to activate apoptosis in grade I-III human glioma cells through the intrinsic and extrinsic pathways.
C1 [Sitarek, Przemyslaw] Medical University of Lodz, Department of Biology and Pharmaceutical Botany, Muszynskiego Street 1, 90-151 Lodz, Poland.
[Skala, Ewa] Medical University of Lodz, Department of Biology and Pharmaceutical Botany, Muszynskiego Street 1, 90-151 Lodz, Poland.
[Toma, Monika] University of Lodz, Department of Molecular GeneticsLodz, Poland.
[Wielanek, Marzena] University of Lodz, Faculty of Biology and Environmental Protection, Department of Plant Physiology and BiochemistryLodz, Poland.
[Szemraj, Janusz] Medical University of Lodz, Department of Medical BiotechnologyLodz, Poland.
[Skorski, Tomasz] Temple University, School of Medicine, Department of Microbiology and Immunology, and Fels Institute for Cancer ResearchPhiladelphia, PA, USA.
[Bialas, J Adam] Medical University of Lodz, 1st Chair of Internal Medicine, Department of Pneumology and AllergyLodz, Poland.
[Sakowicz, Tomasz] The University of Lodz, Department of Genetics and Plant Molecular Biology and BiotechnologyLodz, Poland.
[Kowalczyk, Tomasz] The University of Lodz, Department of Genetics and Plant Molecular Biology and BiotechnologyLodz, Poland.
[Radek, Maciej] Medical University of Lodz, University Hospital WAM-CSW, Department of Neurosurgery, Surgery of Spine and Peripheral NervesLodz, Poland.
[Wysokinska, Halina] Medical University of Lodz, Department of Biology and Pharmaceutical Botany, Muszynskiego Street 1, 90-151 Lodz, Poland.
[Sliwinski, Tomasz] University of Lodz, Department of Molecular GeneticsLodz, Poland.
RP Sitarek, P (reprint author), Medical University of Lodz, Department of Biology and Pharmaceutical Botany, 90-151 Lodz, Poland.
EM przemyslaw.sitarek@umed.lodz.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 679
EP 687
DI 10.1007/s12253-016-0170-6
PG 9
ER
PT J
AU Kuthi, L
Jenei, A
Hajdu, A
Nemeth, I
Varga, Z
Bajory, Z
Pajor, L
Ivanyi, B
AF Kuthi, Levente
Jenei, Alex
Hajdu, Adrienn
Nemeth, Istvan
Varga, Zoltan
Bajory, Zoltan
Pajor, Laszlo
Ivanyi, Bela
TI Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; ISUP grading; Microscopic tumor necrosis; Survival rates; Prognostic factors
ID Renal cell carcinoma; ISUP grading; Microscopic tumor necrosis; Survival rates; Prognostic factors
AB The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a twotiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the fourtiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.
C1 [Kuthi, Levente] University of Szeged, Department of Pathology, Allomas Street 1, H-6725 Szeged, Hungary.
[Jenei, Alex] University of Szeged, Department of Pathology, Allomas Street 1, H-6725 Szeged, Hungary.
[Hajdu, Adrienn] University of Szeged, Department of Pathology, Allomas Street 1, H-6725 Szeged, Hungary.
[Nemeth, Istvan] University of Szeged, Department of Dermatology and Allergology, Koranyi Alley 6, H-6720 Szeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Bajory, Zoltan] University of Szeged, Department of Urology, Kalvaria Lane 57, H-6725 Szeged, Hungary.
[Pajor, Laszlo] University of Szeged, Department of Urology, Kalvaria Lane 57, H-6725 Szeged, Hungary.
[Ivanyi, Bela] University of Szeged, Department of Pathology, Allomas Street 1, H-6725 Szeged, Hungary.
RP Kuthi, L (reprint author), University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
EM kuthi.levente@med.u-szeged.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 689
EP 698
DI 10.1007/s12253-016-0179-x
PG 10
ER
PT J
AU Toth, K
Patai, V
Kalmar, A
Bartak, KB
Nagy, BZs
Galamb, O
Wichmann, B
Tulassay, Zs
Molnar, B
AF Toth, Kinga
Patai, V Arpad
Kalmar, Alexandra
Bartak, Kinga Barbara
Nagy, Brigitta Zsofia
Galamb, Orsolya
Wichmann, Barnabas
Tulassay, Zsolt
Molnar, Bela
TI Circadian Rhythm of Methylated Septin 9, Cell-Free DNA Amount and Tumor Markers in Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SEPT9; Colorectal cancer; Tumormarkers; Circadian rhythm; Cell-free DNA
ID SEPT9; Colorectal cancer; Tumormarkers; Circadian rhythm; Cell-free DNA
AB To determine the level of cell-free DNA (cfDNA), Septin 9 (SEPT9) and tumor markers (CEA, AFP, CA19–9, TPA, CA72–4). Plasma samples were collected four times a day (06:00, 12:00, 18:00, 24:00) from 9 patients with CRC (5 stage I-II, 4 stage III-IV), from one with colorectal adenoma and from one healthy control. CfDNA was isolated, quantified and bisulfite-converted. CfDNA and methylated SEPT9 were determined by RT-PCR. Plasma levels of conventional tumor markers were also measured. The lowest cfDNA concentrations were observed at 24:00 and 18:00 in stage I-III patients. In stage IV samples low cfDNA level (mean 48.2 ng/ml) were observed at several time points (6:00, 12:00, 18:00). The highest cfDNA levels were measured at 6:00 and 12:00 in CRC I-III stages and at 24:00 in stage IV samples (78.65 ng/ ml). Higher in-day differences were found in stage II (43– 48%) than in stage I samples (22%). Interestingly, the highest SEPT9 methylation level was found at 24:00 in most CRC cases, in contrast to the cfDNA levels. At 24:00, all cancer and adenoma cases were positive for SEPT9 methylation. At other time points (6:00, 12:00, 18:00) only 77.7% of CRC samples showed SEPT9 positivity. Stage I samples were SEPT9 positive only at 24:00. CEA and CA19–9 levels displayed correlation with the amount of cfDNA in case of late stage cases. Daytime activity can influence SEPT9 positivity in cases with low concentration of cfDNA. Thus, it may improve screening sensitivity by collecting samples earlier in the morning.
C1 [Toth, Kinga] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Patai, V Arpad] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Bartak, Kinga Barbara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Nagy, Brigitta Zsofia] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Wichmann, Barnabas] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, 1088 Budapest, Hungary.
RP Toth, K (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM drtothkinga@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2017
VL 23
IS 3
BP 699
EP 706
DI 10.1007/s12253-016-0174-2
PG 8
ER
PT J
AU Masood, N
Basharat, Z
Khan, T
Yasmin, A
AF Masood, Nosheen
Basharat, Zarrin
Khan, Tabeer
Yasmin, Azra
TI Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with Various Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE microRNAs; Cancer; miRNA-let7; miRNA-200; miRNA-125
ID microRNAs; Cancer; miRNA-let7; miRNA-200; miRNA-125
AB Involvement of micro RNAs (miRNA) is currently the focus for cancer studies as they effect the post transcriptional expression of different genes. Let-7 family is among the firstly discovered miRNAs that play important role in cell proliferation and dysregulation leading to cell based diseases including cancer. Another family, miRNA-200 prevents transformation of cell to malignant form and tumor formation by interacting with epidermal mesenchymal transition (EMT). Similarly miRNA-125 controls apoptosis and proliferation by affecting multiple genes involved in transcription, immunological defense, resistance against viral and bacterial infections that ultimately leads to cell proliferation, metastasis and finally cancer. All of these micro RNAs are known to be either upregulated or downregulated in various cancers. Current review is focused to elaborate the role of these three families of micro RNAs on different genes that ultimately cause cancer. In conclusion we can say that the miRNAs discussed here are mostly downregulated in various cancers with some exceptions when upregulation of miRNA-125 may be attributed to cancer formation.
C1 [Masood, Nosheen] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Basharat, Zarrin] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Khan, Tabeer] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Yasmin, Azra] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
RP Masood, N (reprint author), Fatima Jinnah Women University, The Mall, Rawalpindi, Pakistan.
EM nosheenmasood@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 707
EP 715
DI 10.1007/s12253-016-0184-0
PG 9
ER
PT J
AU Dundr, P
Nemejcova, K
Laco, J
Skalova, H
Bauerova, L
Matej, R
Fischerova, D
AF Dundr, Pavel
Nemejcova, Kristyna
Laco, Jan
Skalova, Helena
Bauerova, Lenka
Matej, Radoslav
Fischerova, Daniela
TI Anastomosing Hemangioma of the Ovary: A Clinicopathological Study of Six Cases with Stromal Luteinization
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anastomosing hemagioma; Capillary hemangioma; Ovary; Stromal luteinization; Urogenital tract
ID Anastomosing hemagioma; Capillary hemangioma; Ovary; Stromal luteinization; Urogenital tract
AB We report six cases of anastomosing hemangioma of the ovary. All lesions were unilateral and arose in 43 to 81 year old females. In all but one patient, the tumor was asymptomatic and represented incidental finding. The exception was a tumor associated with massive ascites and elevated CA 125. The tumors were, on cut section, spongy and dark violet in color. The size of tumors ranged from 0.5 to 3.5 cm. All lesions showed the same histological features and consisted of capillary sized anastomosing vessels with sinusoid-like pattern intermingled with sporadic medium sized vessels. Interestingly, in all cases there were areas of luteinized cells at the tumor periphery, which ranged from rare small nests to multiple and commonly confluent areas. In one tumor, components of mature adipose tissue were present. Immunohistochemically, all tumors were CD31 and CD34 positive. Other markers examined were negative, including; estrogen receptor, progesterone receptor, androgen receptor, and D2–40. Proliferative activity (Ki-67 index) was very low in all cases. Anastomosing hemangioma is a rare entity, only 8 lesions occurring in ovary has been described from its initial description in 2009.We report six additional cases with their clinicopathological correlation.
C1 [Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Nemejcova, Kristyna] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Laco, Jan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Skalova, Helena] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Bauerova, Lenka] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Matej, Radoslav] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Fischerova, Daniela] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 12800 Prague, Czech Republic.
EM pdundr@seznam.cz
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 717
EP 722
DI 10.1007/s12253-016-0186-y
PG 6
ER
PT J
AU Plones, T
Fischer, M
Hohne, K
Sato, H
Muller-Quernheim, J
Zissel, G
AF Plones, Till
Fischer, Mitja
Hohne, Kerstin
Sato, Hiromi
Muller-Quernheim, Joachim
Zissel, Gernot
TI Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Wilms tumor; Pleural; Asbestos; Pleuropneumonectomy; Decortication; Met; Stemcells; EPP; P/D; Epigenetics; EMT; Epithelial to mesenchymal transition; Cancer; Chemoresistance; Cisplatin; Drug
ID Wilms tumor; Pleural; Asbestos; Pleuropneumonectomy; Decortication; Met; Stemcells; EPP; P/D; Epigenetics; EMT; Epithelial to mesenchymal transition; Cancer; Chemoresistance; Cisplatin; Drug
AB Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.
C1 [Plones, Till] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Fischer, Mitja] Medical Center University of Freiburg, Center for Medicine, Department of PneumologyFreiburg, Germany.
[Hohne, Kerstin] Medical Center University of Freiburg, Center for Medicine, Department of PneumologyFreiburg, Germany.
[Sato, Hiromi] Chiba University, Graduate School of Pharmaceutical Sciences, Department of Clinical Pharmacology&Pharmacometrics, 1-8-1 Inohana, Chuou-ku, 260-8675 Chiba, Japan.
[Muller-Quernheim, Joachim] Medical Center University of Freiburg, Center for Medicine, Department of PneumologyFreiburg, Germany.
[Zissel, Gernot] Medical Center University of Freiburg, Center for Medicine, Department of PneumologyFreiburg, Germany.
RP Plones, T (reprint author), University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic Surgery, Essen, Germany.
EM Till_ploenes@gmx.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 723
EP 730
DI 10.1007/s12253-016-0181-3
PG 8
ER
PT J
AU Li, N
Tan, Q
Jing, W
Luo, P
Tu, J
AF Li, Nandi
Tan, Qian
Jing, Wei
Luo, Ping
Tu, Jiancheng
TI Long Non-Coding RNA SPRY4-IT1 Can Predict Unfavorable Prognosis and Lymph Node Metastasis: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LncRNA; SPRY4-IT1; Lymph node metastasis; Prognosis
ID LncRNA; SPRY4-IT1; Lymph node metastasis; Prognosis
AB Emerging evidences suggested that long noncoding RNAs (lncRNAs) play an interesting role in the tumor development and progression in various types of cancer. The aim of this study was to analyse the potential prognostic value for cancer patients . We systematically searched the reports through PubMed, Web of Science, Medline, CNKI, and the Cochrane Library from inception to March, 2016, and carefully identified according to eligibility criteria. This quantitative meta-analysis collected all relevant articles to investigated the association of SPRY4-IT1 expression status with overall survival (OS) and lymph node metastasis (LNM). A total of 765 patients with cancer from 8 studies were included in the final analysis. The hazard ratio (HR) of OS and the odds ratios (OR) of LNM were calculated to assess the association . The meta-analysis results showed high SPRY4-IT1 expression could predict unfavorable OS in various cancers (pooled HR: 2.18, 95% CI: 1.45–3.27, p = 0.001). Moreover, we found high SPRY4-IT1 expression was related to LNM (pooled OR = 3.86, 95%CI:1.31–11.35, P = 0.01). LncRNA SPRY4-IT1 can serve as a new molecular marker for cancer metastasis and prognosis.
C1 [Li, Nandi] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Tan, Qian] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Jing, Wei] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Luo, Ping] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Tu, Jiancheng] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
RP Tu, J (reprint author), Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory Medicine, Wuhan, China.
EM jianchengtu@whu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 731
EP 736
DI 10.1007/s12253-016-0182-2
PG 6
ER
PT J
AU Hosoya, K
Matsusaka, S
Kashiwada, T
Suzuki, K
Ureshino, N
Sato, A
Miki, Y
Kitera, K
Hirai, M
Hatake, K
Kimura, Sh
Sueoka-Aragane, N
AF Hosoya, Kazuhisa
Matsusaka, Satoshi
Kashiwada, Tomomi
Suzuki, Koichi
Ureshino, Norio
Sato, Akemi
Miki, Yoshio
Kitera, Kazuki
Hirai, Mitsuharu
Hatake, Kiyohiko
Kimura, Shinya
Sueoka-Aragane, Naoko
TI Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Plasma DNA; KRAS mutation; Colorectal neoplasms; Molecular targeted therapy
ID Plasma DNA; KRAS mutation; Colorectal neoplasms; Molecular targeted therapy
AB KRAS mutations have been recognized as predictive markers of primary resistance to anti-EGFR-antibodies in colorectal cancer patients. In addition, newly detected KRAS mutations have been reported to be related with acquired resistance to chemotherapy containing anti-EGFR antibody. Considering this evidence, monitoring of KRAS mutations is indispensable for making treatment decisions, and the method should be non-invasive allowing repeated examinations. Recently, we established a novel automated sensitive detection system for KRAS mutations, named mutation-biased PCR quenching probe system (MBP-QP). The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies. The detection limit of MBP-QP using a control plasmid containing KRAS mutations was 1–9 copies, and 0.05–0.3% mutant plasmid was detectable in a mixture of wild type and mutants. One-hundred twenty colorectal cancer patients were genotyped for KRAS mutations with MBP-QP as well as polymerase chain reaction reverse sequence-specific oligonucleotide (PCR-rSSO), which has already been applied to cancer tissue samples in the clinical setting. Concordance rates between plasma DNA and cancer tissues were 68% with MBP-QP and 66% with PCR-rSSO, indicating that these systems are equivalent in terms of detecting KRAS mutations with plasma DNA. KRAS mutations in plasma DNA were frequently observed in systemic metastatic cancer patients, and in three patients KRAS mutations appeared after chemotherapy containing anti-EGFR antibody. A prospective study is needed for clarifying whether KRAS mutations detected in plasma DNA are predictive markers of treatment efficacy with anti- EGFR antibody.
C1 [Hosoya, Kazuhisa] Saga University, Faculty of Medicine, Department of Internal Medicine, 5-1-1 Nabeshima, 849-8501 Saga, Japan.
[Matsusaka, Satoshi] Cancer Institute Hospital of Japanese Foundation for Cancer Research, Gastroenterological CenterTokyo, Japan.
[Kashiwada, Tomomi] Saga University, Faculty of Medicine, Department of Internal Medicine, 5-1-1 Nabeshima, 849-8501 Saga, Japan.
[Suzuki, Koichi] Jichi Medical University, Saitama Medical Center, Department of SurgerySaitama, Japan.
[Ureshino, Norio] Saga Prefectural Hospital Koseikan, Department of Medical OncologySaga, Japan.
[Sato, Akemi] Saga University, Faculty of Medicine, Department of Internal Medicine, 5-1-1 Nabeshima, 849-8501 Saga, Japan.
[Miki, Yoshio] Japanese Foundation for Cancer Research, The Cancer Institute, Department of Genetic DiagnosisTokyo, Japan.
[Kitera, Kazuki] ARKRAY Inc., Research and Development DivisionKyoto, Japan.
[Hirai, Mitsuharu] ARKRAY Inc., Research and Development DivisionKyoto, Japan.
[Hatake, Kiyohiko] Japanese Foundation for Cancer Research, Cancer Chemotherapy Center, Clinical ChemotherapyTokyo, Japan.
[Kimura, Shinya] Saga University, Faculty of Medicine, Department of Internal Medicine, 5-1-1 Nabeshima, 849-8501 Saga, Japan.
[Sueoka-Aragane, Naoko] Saga University, Faculty of Medicine, Department of Internal Medicine, 5-1-1 Nabeshima, 849-8501 Saga, Japan.
RP Sueoka-Aragane, N (reprint author), Saga University, Faculty of Medicine, Department of Internal Medicine, 849-8501 Saga, Japan.
EM sueokan@cc.saga-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 737
EP 744
DI 10.1007/s12253-016-0175-1
PG 8
ER
PT J
AU Shen, L
Zhao, L
Tang, J
Wang, Z
Bai, W
Zhang, F
Wang, Sh
Li, W
AF Shen, Li
Zhao, Lizhi
Tang, Jiquan
Wang, Zhiwei
Bai, Weisong
Zhang, Feng
Wang, Shouli
Li, Weihua
TI Key Genes in Stomach Adenocarcinoma Identified via Network Analysis of RNA-Seq Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Stomach adenocarcinoma; Gene expression data; Differentially expressed genes; Gene co-expression network; Functional enrichment analysis
ID Stomach adenocarcinoma; Gene expression data; Differentially expressed genes; Gene co-expression network; Functional enrichment analysis
AB RNA-seq data of stomach adenocarcinoma (STAD) were analyzed to identify critical genes in STAD. Meanwhile, relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. Gene expression data of STAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. Relationships with correlation coefficient > 0.6 were retained in the gene co-expression network. Functional enrichment analysis was performed for the genes in the network with DAVID and KOBASS 2.0. Modules were identified using Cytoscape. Relevant small molecules drugs, transcription factors (TFs) and microRNAs (miRNAs) were revealed by using CMAP and WebGestalt databases. A total of 520 DEGs were identified between 285 STAD samples and 33 normal controls, including 244 up-regulated and 276 downregulated genes. A gene co-expression network containing 53 DEGs and 338 edges was constructed, the genes of which were significantly enriched in focal adhesion, ECM-receptor interaction and vascular smooth muscle contraction pathways. Three modules were identified from the gene co-expression network and they were associated with skeletal system development, inflammatory response and positive regulation of cellular process, respectively. A total of 20 drugs, 9 TFs and 6 miRNAs were acquired that may regulate the DEGs. NFAT-COL1A1/ ANXA1, HSF2-FOS, SREBP-IL1RN and miR-26-COL5A2 regulation axes may be important mechanisms for STAD.
C1 [Shen, Li] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Zhao, Lizhi] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Tang, Jiquan] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Wang, Zhiwei] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Bai, Weisong] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Zhang, Feng] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Wang, Shouli] HanZhong Central Hospital, Department of Digestive Surgery, 723000 Hanzhong, Shaanxi, China.
[Li, Weihua] The People’s Hospital in Gansu Province, Center Lab, No, 204 west Donggang Road, 730000 Lanzhou, Gansu Province, China.
RP Li, W (reprint author), The People’s Hospital in Gansu Province, Center Lab, 730000 Lanzhou, China.
EM weiweihhh@aliyun.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 745
EP 752
DI 10.1007/s12253-016-0178-y
PG 8
ER
PT J
AU Lakatos, G
Petranyi,
Szucs, A
Nehez, L
Harsanyi, L
Hegyi, P
Bodoky, Gy
AF Lakatos, Gabor
Petranyi, Agota
Szucs, Attila
Nehez, Laszlo
Harsanyi, Laszlo
Hegyi, Peter
Bodoky, Gyorgy
TI Efficacy and Safety of FOLFIRINOX in Locally Advanced Pancreatic Cancer. A Single Center Experience.
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; Locally advanced; FOLFIRINOX
ID Pancreatic cancer; Locally advanced; FOLFIRINOX
AB The management of locally advanced pancreatic cancer (LAPC) is a major challenge. Although new drugs are available for the treatment of metastatic disease, the optimal treatment of non-metastatic cases remains controversial. The role of neoadjuvant therapy is still a question of debate in this setting. The aim of the study was to prospectively collect and analyse data on efficacy and safety of a modified FOLFIRINOX regimen in LAPC patients treated in a single institution. Another major objective was to assess the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. No bolus fluorouracil was given and a 20% dose reduction of oxaliplatin and irinotecan was applied. Primary GCSF prophylaxis was applied to prevent febrile neutropenia. Thirty-two patients (mean age 60.2 years, range: 40–77 years) have been enrolled into the study. All patients had ECOG performance status of 0 or 1. Best response to therapy was stable disease (SD) or partial regression (PR) in 18 (56.2%) and 6 (18.8%) cases. Two patients (6.3%) underwent surgical resection (100% R0). The most frequent grade 3/4 adverse events were nausea (18.8%), fatigue (12.5%) and diarrhea (12.5%). The incidence of severe neutropenia was 28.1%, with only one documented case of febrile neutropenia. The probability of disease progression was 25% and 50%after 75 and 160 days with 88.4% of possibility of disease progression after 500 days. OS probability was 92.1, 71.5% and 49.5% at 180-, 365 and 540 days. Our data does not support the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. However, due to the high disease control rate observed, FOLFRINOX might be recommended as first line option for the palliative treatment of LAPC. Despite reduced chemotherapy doses significant toxicity has been seen.
C1 [Lakatos, Gabor] Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, 5-7 Albert Florian street, H-1097 Budapest, Hungary.
[Petranyi, Agota] Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, 5-7 Albert Florian street, H-1097 Budapest, Hungary.
[Szucs, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Nehez, Laszlo] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Harsanyi, Laszlo] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Hegyi, Peter] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Bodoky, Gyorgy] Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, 5-7 Albert Florian street, H-1097 Budapest, Hungary.
RP Lakatos, G (reprint author), Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, H-1097 Budapest, Hungary.
EM lakagab@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 753
EP 759
DI 10.1007/s12253-016-0176-0
PG 7
ER
PT J
AU Li, Z
Zhu, K
Gong, X
Vasilescu, S
Sun, Y
Hong, K
Li, H
Li, L
Shan, Y
AF Li, Zhandong
Zhu, Ketong
Gong, Xin
Vasilescu, Steven
Sun, Yu
Hong, Kaiqing
Li, Hao
Li, Lin
Shan, Yaming
TI Inducing Polyclonal Eag1-Specific Antibodies by Vaccination with a Linear Epitope Immunogen and Its Relation to Breast Tumorigenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Eag1; Breast cancer; Polyclonal Eag1-specific antibodies; Immunohistochemical marker
ID Eag1; Breast cancer; Polyclonal Eag1-specific antibodies; Immunohistochemical marker
AB Ether a-go-go 1 (KCNH1, Kv10.1) (Eag1) is a voltage-gated potassium channel, which is commonly overexpressed in tested breast cancer patients. This occurrence makes it a potential molecular marker and a promising tool for breast cancer diagnosis and therapy. In order to explore protective or specific polyclonal antibodies for further research, potential linear epitopes from Eag1 were collected by sequence alignment. The sequence was synthesized and then coupled to the carrier protein keyhole limpet hemocyanin (KLH) for animal immunization. Polyclonal antibodies against Eag1 were produced and purified from the rabbit antisera. Enzyme linked immunosorbent assay (ELISA) and western blot were performed to characterize their specificities. Immunohistochemical staining was carried out on normal and cancerous breast tissue sections using the purified polyclonal Eag1-specific antibodies. The results indicate that the overexpression of Eag1 might be associated with an increased risk of progression to breas t cancer (Grade 1 tissue = 57.89%;Grade 2 tissue = 92.59%;Grade 3 tissue = 100%). These results also suggest that Eag1 gene is a putative growth-promoting gene that might be involved in breast tumorigenesis and development. Eag1 might further be represented as a potential target for some human diseases treatment.
C1 [Li, Zhandong] Jilin Engineering Normal University, College of Biology and Food EngineeringChangchun, Jilin, China.
[Zhu, Ketong] Jilin Engineering Normal University, College of Biology and Food EngineeringChangchun, Jilin, China.
[Gong, Xin] Jilin University, School of Life Sciences, National Engineering Laboratory for AIDS VaccineChangchun, Jilin, China.
[Vasilescu, Steven] University of Technology Sydney, School of Mathematical and Physical Sciences, Materials Analysis Unit, 2007 Ultimo, NSW, Australia.
[Sun, Yu] Jilin Engineering Normal University, College of Biology and Food EngineeringChangchun, Jilin, China.
[Hong, Kaiqing] Jilin Engineering Normal University, College of Biology and Food EngineeringChangchun, Jilin, China.
[Li, Hao] Jilin Engineering Normal University, College of Biology and Food EngineeringChangchun, Jilin, China.
[Li, Lin] Jilin University, China-Japan Union HospitalChangchun, Jilin, China.
[Shan, Yaming] Jilin University, School of Life Sciences, National Engineering Laboratory for AIDS VaccineChangchun, Jilin, China.
RP Li, H (reprint author), Jilin Engineering Normal University, College of Biology and Food Engineering, Changchun, China.
EM muyelee@sina.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 761
EP 767
DI 10.1007/s12253-016-0158-2
PG 7
ER
PT J
AU Chen, J
Wang, Z
Lv, Q
Du, Z
Tan, Q
Zhang, D
Xiong, B
Zeng, H
Gou, J
AF Chen, Jie
Wang, Zu
Lv, Qing
Du, Zhenggui
Tan, Qiuwen
Zhang, Di
Xiong, Bingjun
Zeng, Helin
Gou, Juxiang
TI Comparison of Core Needle Biopsy and Excision Specimens for the Accurate Evaluation of Breast Cancer Molecular Markers: a Report of 1003 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Core needle biopsy; Hormone receptor; HER2; Ki-67; Molecular markers
ID Breast cancer; Core needle biopsy; Hormone receptor; HER2; Ki-67; Molecular markers
AB In this study, we compared the accuracy of marker evaluation in core needle biopsy (CNB) specimens versus excision specimens (ESs) from breast cancer patients. This retrospective study used data collected from the breast cancer database at the West China Hospital, China. Immunohistochemistry (IHC) results from CNB specimens and ESs were compared, using estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 as markers. Molecular subtyping and endocrine therapy usage correlations based on CNB samples and ESs were evaluated. The results obtained from CNB samples and ESs exhibited substantial agreement for the detection of ER (κ = 0.522), PR(κ = 0.441), and HER2 (κ = 0.451), and also influenced endocrine therapy usage. Fair and poor correlations were observed for Ki-67 staining and molecular subtyping (κ = 0.195), respectively. This disagreement might be attributable to a combination of heterogeneity and large tumor size. This study indicates that the discordance rate in molecular marker staining between CNB specimens and ESs is significant enough that results obtained with CNB specimens should be used cautiously or verified using ESs.
C1 [Chen, Jie] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Wang, Zu] Sichuan University, West China Hospital, Tumor Molecular Laboratory, 610041 Chengdu, China.
[Lv, Qing] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Du, Zhenggui] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Tan, Qiuwen] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Zhang, Di] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Xiong, Bingjun] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Zeng, Helin] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
[Gou, Juxiang] Sichuan University, West China Hospital, Department of Breast and Thyroid Surgery, 610041 Chengdu, China.
CR NCCN Clinical Practice Guidelines in Oncology: Breast cancer, 2015, www.NCCN.com.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 769
EP 775
DI 10.1007/s12253-017-0187-5
PG 7
ER
PT J
AU Kuronya, Zs
Sinkovics, I
Agoston, P
Biro, K
Bodrogi, I
Bode, I
Dank, M
Gyergyay, F
Vajdics, T
Kolonics, Zs
Nagyivanyi, K
Ruzsa,
Geczi, L
AF Kuronya, Zsofia
Sinkovics, Istvan
Agoston, Peter
Biro, Krisztina
Bodrogi, Istvan
Bode, Imre
Dank, Magdolna
Gyergyay, Fruzsina
Vajdics, Timea
Kolonics, Zsuzsanna
Nagyivanyi, Krisztian
Ruzsa, Agnes
Geczi, Lajos
TI A Retrospective Analysis of the First 41 mCRPC Patients with Bone Pain Treated with Radium-223 at the National Institute of Oncology in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bone pain; Metastatic castration-resistant prostate cancer (mCRPC); Radium-223
ID Bone pain; Metastatic castration-resistant prostate cancer (mCRPC); Radium-223
AB Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records. The mean age was 72.2 years (SD: 7.1). 24 patients received Radium-223 as first-line treatment (58%), 7 patients as second (17%), 3 as third (7.3%), 6 as (14.6%), and 1 as fifth-line therapy (2.4%). The mean number of cycles administered was 5.5 (SD: 1.1). The most common side effects were anemia (32% grade 1–3), nausea (28%, grade 1), diarrhea (4%, grade 2), thrombocytopenia (4%, grade 3). The mean baseline PSA level was 307.2 ng/ml (SD: 525.7), which increased to a mean value of 728.5 ng/ ml (SD: 1277) by the end of treatment. The baseline mean ALP of 521.1 U/L (SD: 728) decreased to 245.1 U/L (SD: 283.5). The majority of patients experienced a decrease (37%) or complete cessation (43%) of bone pain intensity. In our symptomatic prostate cancer patient population, Radium-223 proved to be efficient in terms of pain relief, with moderate side effects. No PSA response was detected, while alkaline phosphatase levels significantly decreased.
C1 [Kuronya, Zsofia] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Sinkovics, Istvan] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Agoston, Peter] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Biro, Krisztina] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Bodrogi, Istvan] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Bode, Imre] Jahn Ferenc South-Pest HospitalBudapest, Hungary.
[Dank, Magdolna] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Gyergyay, Fruzsina] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Vajdics, Timea] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Kolonics, Zsuzsanna] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Nagyivanyi, Krisztian] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Ruzsa, Agnes] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Geczi, Lajos] National Institute of Oncology, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
RP Kuronya, Zs (reprint author), National Institute of Oncology, H-1122 Budapest, Hungary.
EM kuronyaz@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 777
EP 783
DI 10.1007/s12253-017-0190-x
PG 7
ER
PT J
AU Wang, Y
AF Wang, Yan
TI Transcriptional Regulatory Network Analysis for Gastric Cancer Based on mRNA Microarray
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Transcriptional regulatory network; Transcription factor
ID Gastric cancer; Transcriptional regulatory network; Transcription factor
AB We aimed to screen the differential expressed genes (DEGs) and transcriptional factors (TFs) related to gastric cancer. GSE19826 microarray data downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) and PPI network of DEGs were constructed by the Retrieval of Interacting Genes database. Pathway enrichment analysis of DEGs were performed by Gene Set Enrichment Analysis. Then, the transcriptional regulatory network was constructed based on TRANSFAC database. Finally, regulatory impact factor (RIF) of TF was calculated. We identified 446 DEGs including 209 up- and 237 down-regulated genes. These DEGs were mainly significantly enriched in 5 pathways including ECM receptor interaction (p = 0.013899), spliceosome (p = 0.025591), bladder cancer (p = 0.026316), focal adhesion (p = 0.047809) and WNT signaling pathway (p = 0.048077). PPI network with 247 nodes and 913 edges were constructed and COL5A2 was the hub node. Transcriptional regulatory network with 6 differently expressed TFs, 58 non-differently expressed TFs, 44 DEGs and 735 non-DEGs was constructed. Finally, top 5 TFs including CRX, TFAP4, NKX2–1,MYB and RARG with higher ZRIF were screened. The identified DEGs such as COL5A2 and TOP2A, and TFs including EGR2, FOXM1, NKX2–1 and TFAP4 might be the critical genes and TFs for gastric cancer.
C1 [Wang, Yan] China Medical University, Shengjing Hospital, Department of Gastroenterology, No. 36 Sanhao Road, 110004 Shenyang, China.
RP Wang, Y (reprint author), China Medical University, Shengjing Hospital, Department of Gastroenterology, 110004 Shenyang, China.
EM yan_wang741@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 785
EP 791
DI 10.1007/s12253-016-0159-1
PG 7
ER
PT J
AU Kalantari, E
Asgari, M
Nikpanah, S
Salarieh, N
Lari, HAM
Madjd, Z
AF Kalantari, Elham
Asgari, Mojgan
Nikpanah, Seyedehmoozhan
Salarieh, Naghme
Lari, Hossein Asadi Mohammad
Madjd, Zahra
TI Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Tissue microarray; Immunohistochemistry; CD44; CD133
ID Prostate cancer; Tissue microarray; Immunohistochemistry; CD44; CD133
AB Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demons t r a ted high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.
C1 [Kalantari, Elham] Iran University of Medical Sciences (IUMS), Oncopathology Research Center, Hemmat Street (Highway), Next to Milad Tower, 14496-14530 Tehran, Iran.
[Asgari, Mojgan] Iran University of Medical Sciences (IUMS), Oncopathology Research Center, Hemmat Street (Highway), Next to Milad Tower, 14496-14530 Tehran, Iran.
[Nikpanah, Seyedehmoozhan] Iran University of Medical Sciences (IUMS), Faculty of Medicine, Department of PathologyTehran, Iran.
[Salarieh, Naghme] Iran University of Medical Sciences (IUMS), Faculty of Medicine, Department of PathologyTehran, Iran.
[Lari, Hossein Asadi Mohammad] University of British Columbia (UBC), Faculty of Medicine, Department of Cellular, Anatomical and Physiological SciencesVancouver, BC, Canada.
[Madjd, Zahra] Iran University of Medical Sciences (IUMS), Oncopathology Research Center, Hemmat Street (Highway), Next to Milad Tower, 14496-14530 Tehran, Iran.
RP Asgari, M (reprint author), Iran University of Medical Sciences (IUMS), Oncopathology Research Center, 14496-14530 Tehran, Iran.
EM mojgan_asgari@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 793
EP 802
DI 10.1007/s12253-016-0169-z
PG 10
ER
PT J
AU Di Michele, J
Rotondo, F
Kovacs, K
Syro, VL
Yousef, MG
Cusimano, DM
Di Ieva, A
AF Di Michele, Joseph
Rotondo, Fabio
Kovacs, Kalman
Syro, V Luis
Yousef, M George
Cusimano, D Michael
Di Ieva, Antonio
TI Vasculogenic Mimicry in Clinically Non-functioning Pituitary Adenomas: a Histologic Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarkers; Pathology; Pituitary adenoma; Microvascularity; Vasculogenic mimicry
ID Biomarkers; Pathology; Pituitary adenoma; Microvascularity; Vasculogenic mimicry
AB The term "vasculogenic mimicry" (VM) refers to the phenomenon in which vascular-like channels, which are not lined by endothelial cells, are formed in tumors. Since its discovery in 1999, it has been observed in several tumor types and is proposed to provide blood perfusion to tumors in absence of coapted or neo-angiogenic blood vessels. Pituitary tumors are generally slow growing, benign adenomas which are less vascularized than the normal pituitary gland. To date, VM in pituitary adenomas has not been described. In this histological study, we assessed the presence of VM in a series of surgically resected clinically non-functioning pituitary adenomas (NFPAs) using CD34 and Periodic Acid-Schiff (PAS) double staining. To identify VM, slides were assessed for the presence of CD34- negative and PAS-positive channels indicating that they were not lined by endothelial cells. The histological staining pattern suggestive of VM was noted in 22/49 (44.9%) of the specimens studied. VM was observed in both recurring and non-recurring NFPAs. The incidence of VM present varied from case to case and within groups. There was no association between the presence of VM and gender, tumor size, Ki-67 index, recurrence or cavernous sinus invasion. VM was not noted in cases of nontumorous pituitaries. Our findings suggest the existence of a complementary perfusion system in pituitary adenomas, implying potential clinical implications with respect to response to therapy and clinical course. Further research is warranted to confirm the presence of VM in pituitary adenomas to elucidate its clinical relevance in patients diagnosed with a pituitary adenoma.
C1 [Di Michele, Joseph] St. Michael’s Hospital, Department of SurgeryToronto, ON, Canada.
[Rotondo, Fabio] St. Michael’s Hospital, Department of Laboratory Medicine, 30 Bond Street, M5B1W8 Toronto, ON, Canada.
[Kovacs, Kalman] St. Michael’s Hospital, Department of Laboratory Medicine, 30 Bond Street, M5B1W8 Toronto, ON, Canada.
[Syro, V Luis] Hospital Pablo Tobon Uribe and Clinica Medellin, Department of NeurosurgeryMedellin, Colombia.
[Yousef, M George] St. Michael’s Hospital, Department of Laboratory Medicine, 30 Bond Street, M5B1W8 Toronto, ON, Canada.
[Cusimano, D Michael] St. Michael’s Hospital, Department of SurgeryToronto, ON, Canada.
[Di Ieva, Antonio] Macquarie University Hospital, Australian School of Advanced Medicine, Department of NeurosurgerySydney, Australia.
RP Rotondo, F (reprint author), St. Michael’s Hospital, Department of Laboratory Medicine, M5B1W8 Toronto, Canada.
EM rotondof@smh.ca
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 803
EP 809
DI 10.1007/s12253-017-0196-4
PG 7
ER
PT J
AU Rath-Wolfson, L
Bubis, G
Shtrasburg, Sh
Shvero, A
Koren, R
AF Rath-Wolfson, Lea
Bubis, Golan
Shtrasburg, Shmuel
Shvero, Asaf
Koren, Rumelia
TI Seminal Tract Amyloidosis: Synchronous Amyloidosis of the Seminal Vesicles, Deferent Ducts and Ejaculatory Ducts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Senile seminal vesicle amyloidosis (SSVA); Ejaculatory duct amyloidosis; Spermatic duct amyloidosis; Senile seminal tract amyloidosis (SSTA)
ID Senile seminal vesicle amyloidosis (SSVA); Ejaculatory duct amyloidosis; Spermatic duct amyloidosis; Senile seminal tract amyloidosis (SSTA)
AB Senile Seminal Vesicle Amyloidosis (SSVA) increases with age. Involvement of the whole seminal tract, i.e. the seminal vesicles, ejaculatory and deferent ducts was first reported by us in the International Symposium on Amyloidosis 1998. Since then we encountered four more cases of SSVA. In all these cases the ejaculatory and deferent ducts were also involved by amyloid. The amyloid was located mostly sub-epithelially, stained positively with Congo red, gave green birefringence under polarized light and was permanganate sensitive, slightly positive for lactoferrin immunostaining and negative for all known amyloid types. In recent years the amyloid was found to be derived from Semenogelin I, a major constituent of the seminal fluid which is present in the epithelial cells of the seminal vesicle and vas deference. This would explain the deposition of amyloid not only in the seminal vesicles but also in the deferent an ejaculatory ducts which transport the seminal fluid. In a review of the literature we found three more articles on SSVA in which the amyloid was not limited to the seminal vesicles alone. We propose to designate this type of amyloid as "Senile seminal Tract Amyloidosis" (SSTA) instead of "Senile Seminal Vesicle Amyloidosis (SSVA)".
C1 [Rath-Wolfson, Lea] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
[Bubis, Golan] University of Nicosia, Medicine Program, St. George’s University of London, 93 Agiou Nikolau Street, Egnomi, 2408 Nicosia, Cyprus.
[Shtrasburg, Shmuel] Sheba Medical Center, Heller Institute of Medical ResearchTel-Hashomer, Israel.
[Shvero, Asaf] Sheba Medical Center, Department of UrologyTel-Hashomer, Israel.
[Koren, Rumelia] A, Rabin Medical Center (Golda Campus), Department of PathologyPetach Tikvah, Israel.
RP Bubis, G (reprint author), University of Nicosia, Medicine Program, St. George’s University of London, 2408 Nicosia, Cyprus.
EM bubisgolan@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 811
EP 814
DI 10.1007/s12253-017-0193-7
PG 4
ER
PT J
AU Fkih M’hamed, I
Privat, M
Trimeche, M
Penault-Llorca, F
Bignon, YJ
Kenani, A
AF Fkih M’hamed, Insaf
Privat, Maud
Trimeche, Mounir
Penault-Llorca, Frederique
Bignon, Yves-Jean
Kenani, Abderraouf
TI miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNAs; Human triple negative breast cancer; LNM; Biomarkers
ID MicroRNAs; Human triple negative breast cancer; LNM; Biomarkers
AB MicroRNAs (miRNAs) are small non-coding RNAs composed of 18–25 nucleotides that can posttranscriptionally regulate gene expression and have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. About 1000 genes in humans encode miRNAs, which account for approximately 3% of the human genome, and up to 30% of human protein coding genes may be regulated by miRNAs. The objective of this article is to evaluate the expression profile of four miRNAs previously implicated in triple negative breast cancer: miR-10b, miR-26a, miR-146a and miR-153, and to determine their possible interaction in triple negative and non triple negative breast cancer based on clinical outcome and the expression of BRCA1. 24 triplenegative and 13 non triple negative breast cancer cases, were studied by q-RT-PCR and immunohistochemistry to determine the expression of the four studied miRNAs and the BRCA1 protein, respectively. We observed that the BRCA1 protein was absent in 62.5% of the triple negative cases. Besides, the miR-146a and miR-26a were over expressed in triple negative breast cancer. These two miRNAs, miR-10b and miR-153 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma. All the analyzed microRNAs were not associated with the expression of BRCA1 in our conditions. Our work provides evidence that miR-146a, miR-26a, miR-10b and miR-153 could be defined as biomarkers in triple negative breast cancer to predict lymph node metastases (LNM).
C1 [Fkih M’hamed, Insaf] Centre Jean Perrin, Departement of oncogenetics, 63011 Clermont-Ferrand, France.
[Privat, Maud] Centre Jean Perrin, Departement of oncogenetics, 63011 Clermont-Ferrand, France.
[Trimeche, Mounir] Farhat Hached Hospital, Department of Pathology, 4000 Sousse, Tunisia.
[Penault-Llorca, Frederique] University of Auvergne, EA4677 ERTICAClermont-Ferrand, France.
[Bignon, Yves-Jean] Centre Jean Perrin, Departement of oncogenetics, 63011 Clermont-Ferrand, France.
[Kenani, Abderraouf] University of Monastir, Faculty of Medicine of Monastir, Laboratory of Biochemistry Research unit UR 12ES08 Cell Signaling and Disease, 5019 Monastir, Tunisia.
RP Kenani, A (reprint author), University of Monastir, Faculty of Medicine of Monastir, Laboratory of Biochemistry Research unit UR 12ES08 Cell Signaling and Disease, 5019 Monastir, Tunisia.
EM raouf.kenani@fmm.rnu.tn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 815
EP 827
DI 10.1007/s12253-017-0188-4
PG 13
ER
PT J
AU Chen, J
Zhang, Sh
Lin, Y
Yang, B
Cao, J
AF Chen, Jia
Zhang, Shoude
Lin, Yi
Yang, Beibei
Cao, Jiang
TI Antitumor Efficacy of SLPI Promoter-Controlled Expression of Artificial microRNA Targeting EGFR in a Squamous Cell Carcinoma Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; Gene therapy; microRNA; Recombinant adenovirus; SLPI
ID EGFR; Gene therapy; microRNA; Recombinant adenovirus; SLPI
AB The purpose of this study was to develop a recombinant adenovirus with secretory leukoprotease inhibitor (SLPI) promoter-controlled expression for gene therapy of squamous cell carcinoma (SCC). An artificial microRNA targeting epidermal growth factor receptor (EGFR) was designed, and used to construct a replication-defective recombinant adenovirus with SLPI promoter-controlled expression. The silencing efficiency of this vector (Ad-SLPI-EGFRamiR) was detected in Hep-2 cells. Western blotting showed that the expression of 170 kD EGFR was significantly reduced in Hep- 2 cells 72 h after infection with Ad-SLPI-EGFRamiR. At a multiplicity of infection (MOI) of 200 pfu/cell, proliferation of Hep-2 cells was highly inhibited by Ad-SLPI-EGFRamiR (inhibition rate: ~70%). The apoptosis rate of Hep-2 cells at 72 h after infection with Ad-SLPI-EGFRamiR at a MOI 35 pfu/cell was 32.8%. The adenovirus constructed was able to specifically inhibit the growth of SCC cells in vitro.
C1 [Chen, Jia] Zhejiang University, School of Medicine, The Second Affiliated Hospital, Department of Otorhinolaryngology, 88 Jiefang Road, 310009 Hangzhou, China.
[Zhang, Shoude] Zhejiang University, School of Medicine, The Second Affiliated Hospital, Department of Otorhinolaryngology, 88 Jiefang Road, 310009 Hangzhou, China.
[Lin, Yi] Zhejiang University, School of Medicine, The Second Affiliated Hospital, Department of Otorhinolaryngology, 88 Jiefang Road, 310009 Hangzhou, China.
[Yang, Beibei] Zhejiang University, School of Medicine, The Second Affiliated Hospital, Department of Otorhinolaryngology, 88 Jiefang Road, 310009 Hangzhou, China.
[Cao, Jiang] Zhejiang University, School of Medicine, The Second Affiliated Hospital, Clinical Research Center, 88 Jiefang Road, 310009 Hangzhou, China.
RP Cao, J (reprint author), Zhejiang University, School of Medicine, The Second Affiliated Hospital, Clinical Research Center, 310009 Hangzhou, China.
EM caoj@zju.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 829
EP 835
DI 10.1007/s12253-016-0160-8
PG 7
ER
PT J
AU Karabon, L
Tupikowski, K
Tomkiewicz, A
Partyka, A
Pawlak-Adamska, E
Wojciechowski, A
Kolodziej, A
Dembowski, J
Zdrojowy, R
Frydecka, I
AF Karabon, Lidia
Tupikowski, Krzysztof
Tomkiewicz, Anna
Partyka, Anna
Pawlak-Adamska, Edyta
Wojciechowski, Adam
Kolodziej, Anna
Dembowski, Janusz
Zdrojowy, Romuald
Frydecka, Irena
TI Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CTLA-4; CD28; Gene polymorphisms; Prostate cancer
ID CTLA-4; CD28; Gene polymorphisms; Prostate cancer
AB The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA- 4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA- 4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.
C1 [Karabon, Lidia] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Tupikowski, Krzysztof] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Tomkiewicz, Anna] Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Partyka, Anna] Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Pawlak-Adamska, Edyta] Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
[Wojciechowski, Adam] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Kolodziej, Anna] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Dembowski, Janusz] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Zdrojowy, Romuald] Wroclaw Medical University, Department of Urology and Oncological Urology, Borowska 213, 50-556 Wroclaw, Poland.
[Frydecka, Irena] Hirszfeld Institute of Immunology and Experimental Therapy, Department of Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
RP Karabon, L (reprint author), Wroclaw Medical University, Department of Urology and Oncological Urology, 50-556 Wroclaw, Poland.
EM lkarabon@iitd.pan.wroc.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 837
EP 843
DI 10.1007/s12253-016-0180-4
PG 7
ER
PT J
AU Roychowdhury, A
Samadder, S
Islam, SM
Chaudhury, K
Roy, A
Banerjee, D
Mandal, R
Basu, SP
Roychoudhury, S
Panda, KCh
AF Roychowdhury, Anirban
Samadder, Sudip
Islam, Saimul Md
Chaudhury, Kalyansree
Roy, Anup
Banerjee, Dipanwita
Mandal, Ranajit
Basu, S Partha
Roychoudhury, Susanta
Panda, Kumar Chinmay
TI Identification of Changes in the Human Papilloma Virus 16 (HPV16) Genome During Early Dissemination of Cervical Cancer Cells May Complement Histological Diagnosis of Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine cervical carcinoma; Disseminated tumor cells (DTCs); Lymph node metastasis; Human papilloma virus (HPV) type 16; HPV16 integration; HPV16 methylation
ID Uterine cervical carcinoma; Disseminated tumor cells (DTCs); Lymph node metastasis; Human papilloma virus (HPV) type 16; HPV16 integration; HPV16 methylation
AB Cancer of the uterine cervix (CACX) is one of the most common carcinoma affecting women worldwide. During treatment, histologically lymph node (LN) metastasis and presence of HPV DNA in blood plasma act as a major prognostic factor. Despite the lack of apparent LN involvement, some early-invasive CACX patients have shown recurrences and poor survival. This is suggestive of undetected early dissemination of cancer cells characterized by presence of HPV DNA in histologically non-metastatic LNs which finally progresses into histologically visible metastasis. This present study investigated the status and origin of HPV genome during early dissemination by molecular analysis in primary tumor (PT), histologically non-metastatic pelvic lymph nodes (LNs) and blood plasma (BP) of same patient. First, CACX patients showing signs of early dissemination was identified by detection of HPV in PT (n = 22) and their corresponding histologically non-metastatic pelvic LNs (n = 45) and BP (n = 18) followed by typing of HPV16/18. This was followed by comparative analysis of the physical, copy number and methylation (enhancer/early/late) status of HPV16 genome present in LNs and BP with that of PT. Our study revealed for the first time that the HPV16 genome were frequently present in the integrated form though the copy number was low in both non-metastatic LNs and BP. However, the methylation pattern of PT was discordant with that of corresponding LNs and BP in majority of the cases. Critical assessment of HPV16 profiles established that the presence of hrHPV may be due to the early dissemination of PT cells having significant pathological implications.
C1 [Roychowdhury, Anirban] Chittaranjan National Cancer Institute, Department of Oncogene RegulationKolkata, India.
[Samadder, Sudip] Chittaranjan National Cancer Institute, Department of Oncogene RegulationKolkata, India.
[Islam, Saimul Md] Chittaranjan National Cancer Institute, Department of Oncogene RegulationKolkata, India.
[Chaudhury, Kalyansree] Burdwan Medical College, Burdwan, Department of Gynecology and ObstetricsBurdwan, West Bengal, India.
[Roy, Anup] North Bengal Medical College and Hospital, Department of PathologySiliguri, West Bengal, India.
[Banerjee, Dipanwita] Chittaranjan National Cancer Institute, Department of Gynecology OncologyKolkata, India.
[Mandal, Ranajit] Chittaranjan National Cancer Institute, Department of Gynecology OncologyKolkata, India.
[Basu, S Partha] World Health Organization (WHO), International Agency for Research on Cancer (IARC), India Screening Group (SCR), Early Detection and Prevention Section (EDP)Lyon, France.
[Roychoudhury, Susanta] Saroj Gupta Cancer Centre & Research InstituteKolkata, India.
[Panda, Kumar Chinmay] Chittaranjan National Cancer Institute, Department of Oncogene RegulationKolkata, India.
RP Panda, KCh (reprint author), Chittaranjan National Cancer Institute, Department of Oncogene Regulation, Kolkata, India.
EM ckpanda.cnci@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 845
EP 852
DI 10.1007/s12253-017-0189-3
PG 8
ER
PT J
AU Sumegi, K
Duga, B
Melegh, IB
Banfai, Zs
Kovesdi, E
Maasz, A
Melegh, B
AF Sumegi, Katalin
Duga, Balazs
Melegh, I Bela
Banfai, Zsolt
Kovesdi, Erzsebet
Maasz, Anita
Melegh, Bela
TI Marked Differences of Haplotype Tagging SNP Distribution, Linkage, and Haplotype Profile of APOA5 Gene in Roma Population Samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE APOA5; Triglyceride; Haplotype; Linkage disequilibrium; Roma
ID APOA5; Triglyceride; Haplotype; Linkage disequilibrium; Roma
AB Roma people are underprivileged, neglected population worldwide, with severe healthcare problems. They have significantly increased prevalence of cardiovascular morbidity, presumably related to their poor social status, alcohol consumption and smoking habits. Assuming that genetic background also plays a role in their susceptibility for cardiovascular diseases, we hypothesized that APOA5 gene polymorphisms, an important role-player in lipid metabolism and in the development of metabolic syndrome and cardio/ cerebrovascular events, may also be involved. We examined four APOA5 polymorphisms in 363 Roma and 404 Hungarian DNA samples. For rs662799, rs2266788, rs207560 and rs3135506 we found elevated plasma triglyceride levels in the risk allele carriers compared to non-carriers in both populations. At least a two-fold significant increase was detected in minor allele frequencies in Roma when compared to Hungarians, except the rs2266788 variant. Haplotype analysis revealed significant increase of APOA5*2, APOA5*4 in Roma, as opposed to the higher levels of APOA5*5 found in Hungarians. Different linkage disequilibrium was found between rs207560 and rs3135506 variants in Roma compared to Hungarians. The profound differences observed in almost all APOA5 polymorphisms in Roma require special attention, since these variants are known to associate with cardio/cerebrovascular susceptibility.
C1 [Sumegi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Duga, Balazs] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Melegh, I Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Banfai, Zsolt] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Kovesdi, Erzsebet] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti Street 12, H-7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
EM melegh.bela@pte.hu
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Sipeky C, Csongei V, Jaromi L, Safrany E, Maasz A, Takacs I, Beres J, Fodor L, Szabo M, Melegh B, 2011, Genetic variability and haplotype profile of MDR1, ABCB1, in Roma and Hungarian population samples with a review of the literature. Drug Metab Pharmacokinet 26(2):206–215
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 853
EP 861
DI 10.1007/s12253-017-0197-3
PG 9
ER
PT J
AU Papp, G
Mihaly, D
Sapi, Z
AF Papp, Gergo
Mihaly, Dora
Sapi, Zoltan
TI Unusual Signal Patterns of Break-apart FISH Probes Used in the Diagnosis of Soft Tissue Sarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Atypical FISH pattern; Break-apart probe; Soft tissue sarcoma
ID Atypical FISH pattern; Break-apart probe; Soft tissue sarcoma
AB Break-apart FISH probes are the most popular and reliable type of FISH probes used to confirm certain pathological diagnoses. The interpretation is usually easy, however, in some instances it is not so unequivocal. Our aim was to reveal and elucidate the problems occurring in the process of evaluation of the break-apart probe results. Altogether 301 soft tissue sarcomas with confirmed molecular tests using breakapart probes were assessed to reveal the frequency and type of unusual signal pattern. Among 89 synovial sarcoma (SS18) 11%, 12 alveolar rhabdomyosarcoma (FOXO1) 50%, 53 myxoid liposarcoma (DDIT3) 7.5%, 6 low grade fibromyxoid sarcoma (FUS) 67%, 93 Ewing sarcoma (EWSR1) 3%, 12 clear cell sarcoma (EWSR1) 8%, 5 desmoplastic small round cell tumor (EWSR1) 0%, 9 extraskeletal myxoid chondrosarcoma (EWSR1) 0%, 2 myoepithelial carcinoma (EWSR1) 50%, 14 dermatofibrosarcoma protuberans (COL1A1) 86% and 6 nodular fasciitis (USP6) 17% atypical break-apart signals were detected. Despite the unusual signal pattern type, the fusion genes were detected using either metaphase FISH, interphase FISH with translocation/TriCheck probe or RT-PCR methods. Although the interpretation problems in the process to evaluate the break-apart probe results is well known from sporadic case reports, a systemic overview to detect their frequency has not been performed so far. In our work we highlighted the relative frequency of this problem and pinpointed those signal-patterns which, despite their unusual appearance, can still confirm the diagnosis.
C1 [Papp, Gergo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Mihaly, Dora] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Sapi, Z (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM sapi.zoltan.dr@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 863
EP 871
DI 10.1007/s12253-017-0200-z
PG 9
ER
PT J
AU Raza, Y
Khan, A
Khan, IA
Khan, S
Akhtar, ShS
Mubarak, M
Ahmed, A
Kazmi, USh
AF Raza, Yasir
Khan, Adnan
Khan, Iqbal Asif
Khan, Saeed
Akhtar, Shakeel Syed
Mubarak, Muhammad
Ahmed, Ayaz
Kazmi, Urooj Shahana
TI Combination of Interleukin 1 Polymorphism and Helicobacter pylori Infection: an Increased Risk of Gastric Cancer in Pakistani Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Helicobacter pylori; Gastritis; Gastric cancer; Cytokines; Polymorphism
ID Helicobacter pylori; Gastritis; Gastric cancer; Cytokines; Polymorphism
AB Helicobacter pylori is one of the major risk factors involved in the development ofgastritis and gastric cancer (GC). H. pylori infection leads to increased production of pro-inflammatory cytokines by the host. Carriage of specific polymorphisms in cytokine genesmay be associatedwith host susceptibility to the development of GC. We investigated the role of host genetic factors including polymorphisms of IL-1B and IL-1RN in correlation with gastritis and GC in H. pylori infected Pakistani population. A total of 230 gastritis cases and 100 GC cases were genotyped for IL 1B-511 and IL- 1RN penta-allelic variable number of tandem repeats (VNTRs). A combination of IL-1B-511*T and IL-1RN*2 alleles (OR 19.064; 95% CI 2.319–156.7; p = 0.001) in H. pylori infected individuals had markedly increased risk of GC development. In Pakistani population, an increased risk of GC development is associated with the carriage of IL-1B- 511*T and IL-1RN*2 alleles. Synergistic effect of H. pylori infection and IL-1B-511*T/IL-1RN*2 genotypes was also observed in association with significantly higher risk of developing GC. Further prospective and large scale studies are needed to establish the clinical impact of these findings.
C1 [Raza, Yasir] Deewan Farooq Medical Complex, Sindh Institute of Urology and Transplantation, Stem Cell Research Laboratory, Chand Bibi RoadKarachi, Pakistan.
[Khan, Adnan] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
[Khan, Iqbal Asif] Dow University of Health and Sciences, Department of Molecular PathologyKarachi, Pakistan.
[Khan, Saeed] Dow University of Health and Sciences, Department of Molecular PathologyKarachi, Pakistan.
[Akhtar, Shakeel Syed] Civil Hospital Karachi, Department of Surgery and MedicineKarachi, Pakistan.
[Mubarak, Muhammad] Sindh Institute of Urology and Transplantation, Department of HistopathologyKarachi, Pakistan.
[Ahmed, Ayaz] Dr. Panjwani Center For Molecular Medicine And Drug ResearchKarachi, Pakistan.
[Kazmi, Urooj Shahana] University of Karachi, Department of Microbiology, Immunology and Infectious Diseases Research LaboratoryKarachi, Pakistan.
RP Raza, Y (reprint author), Deewan Farooq Medical Complex, Sindh Institute of Urology and Transplantation, Stem Cell Research Laboratory, Karachi, Pakistan.
EM yaaasirz@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 873
EP 880
DI 10.1007/s12253-017-0191-9
PG 8
ER
PT J
AU Liu, K
Wan, J
Bei, Y
Chen, X
Lu, M
AF Liu, Kaitai
Wan, Juefeng
Bei, Yanping
Chen, Xue
Lu, Miaozhen
TI Prognostic Impact of Different Histological Types on Gastric Adenocarcinoma: a Surveillance, Epidemiology, and End Results Database Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric carcinoma; Mucinous adenocarcinoma; Signet ring cell carcinoma; Survival; SEER
ID Gastric carcinoma; Mucinous adenocarcinoma; Signet ring cell carcinoma; Survival; SEER
AB The clinicopathological characteristics and prognosis of gastric mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRC) are still controversial.We designed our study to evaluate the clinicopathologic features and prognosis of MAC, SRC and ordinary gastric adenocarcinoma (OGAC) by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database. The 5-year overall survival (OS) of patients with SRC was significantly lower than that of patients with MAC (P = 0.001) and OGAC (P < 0.001), and there was no significant difference in 5- year OS between MAC and OGAC (P = 0.804). Furthermore, there were no significant differences of 5-years OS among these three groups at stage I, II and III (all P > 0.05) and no significant difference between MAC and OGAC at stage IV (P = 0.110). Patients in SRC group had significantly worse survival than those in MAC and OGAC at stage IV (both P = 0.008), with 5-year OS of 3.3%, 5.8%, and 5.8%, respectively. However, the histological type was not found to be an independent prognostic factor of gastric cancer according to the multivariate analysis with Cox regression.
C1 [Liu, Kaitai] Ningbo Medical Center, Lihuili Hospital, Department of Radiation Oncology, No. 57, Xing’Ning Road, 315041 Ningbo, China.
[Wan, Juefeng] Fudan University, Shanghai Cancer Center, Department of Radiation OncologyShanghai, China.
[Bei, Yanping] Ningbo Medical Center, Lihuili Hospital, Department of Radiation Oncology, No. 57, Xing’Ning Road, 315041 Ningbo, China.
[Chen, Xue] Ningbo Medical Center, Lihuili Hospital, Department of Radiation Oncology, No. 57, Xing’Ning Road, 315041 Ningbo, China.
[Lu, Miaozhen] Ningbo Medical Center, Lihuili Hospital, Department of Radiation Oncology, No. 57, Xing’Ning Road, 315041 Ningbo, China.
RP Lu, M (reprint author), Ningbo Medical Center, Lihuili Hospital, Department of Radiation Oncology, 315041 Ningbo, China.
EM lmz2005@yeah.net
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 881
EP 887
DI 10.1007/s12253-017-0198-2
PG 7
ER
PT J
AU Farkas, T
Muller, J
Erdelyi, JD
Csoka, M
Kovacs, TG
AF Farkas, Tamas
Muller, Judit
Erdelyi, J Daniel
Csoka, Monika
Kovacs, T Gabor
TI Absolute Lymphocyte Count (ALC) after Induction Treatment Predicts Survival of Pediatric Patients with Acute Lymphoblastic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALC; ALL; Survival
ID ALC; ALL; Survival
AB Absolute Lymphocyte Count (ALC) has been recently established as a prognostic factor of survival in pediatric Acute Lymphoblastic Leukemia (ALL). A retrospective analysis of 132 patients treated according the BFM – ALLIC 2002 protocol was performed in a single institution. A possible association between ALC values and Overall Survival (OS) or Event-Free Survival (EFS) was evaluated at multiple time points during induction chemotherapy. ALC higher than 350 cells/μL measured on the 33th day of induction was associated with better Overall- and Event-Free Survival in both Kaplan-Meier (OS 88.6% vs. 40%; p < 0.001 / EFS 81.6% vs. 30%; p < 0.001) and Cox regression (OS HR 8.77 (3.31– 23.28); p < 0.001) and EFS HR 6.61 (2.79–15.63); p < 0.001) analyses. There was no association between survival and measured ALC values from earlier time points (day of diagnosis, days 8 and 15) of induction therapy. Patients with low ALC values tend to have higher risk (MR or HR groups) and a higher age at diagnosis (>10 years). With help of day 33 ALC values of 350 cells/μL cutoff it was possible to refine day 33 flow cytometry (FC) Minimal Residual Disease (MRD) results within the negative cohort: higher ALC values were significantly associated with better survival. ALC on day 33 (350 cells/μL) remained prognostic for OS and EFS in multivariate analysis after adjusting it for age, cytogenetics, immunophenotype and FC MRD of induction day 33. According to these findings ALC on day 33 of induction is a strong predictor of survival in pediatric ALL.
C1 [Farkas, Tamas] Semmelweis UniversityBudapest, Hungary.
[Muller, Judit] Semmelweis UniversityBudapest, Hungary.
[Erdelyi, J Daniel] Semmelweis UniversityBudapest, Hungary.
[Csoka, Monika] Semmelweis UniversityBudapest, Hungary.
[Kovacs, T Gabor] Semmelweis UniversityBudapest, Hungary.
RP Kovacs, TG (reprint author), Semmelweis University, Budapest, Hungary.
EM kovi2@hotmail.com
CR Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, CarrollWL, 2012, Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report fromthe children’s oncology group. J Clin Oncol 30:1663–1669
Pui CH, Campana D, Pei D, BowmanWP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Raimondi SC, OnciuM, Coustan-Smith E, Kun LE, Jeha S, Cheng C, Howard SC, Simmons V, Bayles A, Metzger ML, Boyett JM, Leung W, Handgretinger R, Downing JR, Evans WE, Relling MV, 2009, Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 360: 2730–2741
Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB, Schmiegelow K, Escherich G, Horibe K, Benoit YC, Izraeli S, Yeoh AE, Liang DC, Downing JR, Evans WE, Relling MV, Mullighan CG, 2015, Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol 33:2938–2948
Basso G, Veltroni M, Valsecchi MG, Dworzak MN, Ratei R, Silvestri D, Benetello A, Buldini B, Maglia O, Masera G, Conter V, Arico M, Biondi A, Gaipa G, 2009, Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 27:5168–5174
Gaipa G, Cazzaniga G, Valsecchi MG, Panzer-Grumayer R, Buldini B, Silvestri D, Karawajew L, Maglia O, Ratei R, Benetello A, Sala S, Schumich A, Schrauder A, Villa T, Veltroni M, Ludwig WD, Conter V, Schrappe M, Biondi A, Dworzak MN, Basso G, 2012, Time point-dependent concordance of flow cytometry and real-time quantitative polymerase chain reaction for minimal residual disease detection in childhood acute lymphoblastic leukemia. Haematologica 97:1582–1593
Stary J, ZimmermannM, CampbellM, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, RiehmH, Masera G, SchrappeM(2014, Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol 32:174–184
Anoceto Martinez A, Gonzalez Otero A, Guerchicoff de Svarch E, Arencibia Nunez A, Jaime JC, Dorticos E, Sarduy S, Gonzalez L, 2012, Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia. An Pediatr 76:10e1–10e6
Behl D, Porrata LF, Markovic SN, Letendre L, Pruthi RK, Hook CC, Tefferi A, Elliot MA, Kaufmann SH, Mesa RA, Litzow MR, 2006, Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia. Leukemia 20:29–34
Cheng Y, Luo Z, Yang S, Jia M, Zhao H, XuW, Tang Y, 2015, The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood Blineage acute lymphoblastic leukemia. Leuk Res 39:144–150
De Angulo G, Hernandez M, Morales-Arias J, Herzog CE, Anderson P, Wolff J, Kleinerman ES, 2007, Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma. J Pediatr Hematol Oncol 29:48–52
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 889
EP 897
DI 10.1007/s12253-017-0192-8
PG 9
ER
PT J
AU Ma, G
Li, Q
Dai, W
Yang, X
Sang, A
AF Ma, Gang
Li, Qianjun
Dai, Weijie
Yang, Xiaozhong
Sang, Aiyu
TI Prognostic Implications of miR-302a/b/c/d in Human Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; miR-302a/b/c/d; Clinicopathological feature; Disease-free survival; Overall survival
ID Gastric cancer; miR-302a/b/c/d; Clinicopathological feature; Disease-free survival; Overall survival
AB Background: The microRNA (miR)-302 family consisting four members, miR-302a, miR-302b, miR-302c and miR-302d, plays an important role in diverse biological processes, and regulates many pathological changes, including cancer. However, the involvement of the miR-302 family into human gastric cancer (GC) remains unclear. The aim of this study was to investigate the expression patterns of miR- 302a/b/c/d and determine their clinical significance in GC. Materials and methods: Expression levels of miR-302a/b/c/d in 160 pairs of human GC and matched normal mucosa tissues were detected by quantitative real-time polymerase chain reaction. Then, the associations of miR-302a/b/c/d expression with various clinicopathological characteristics and patients’ prognosis were statistically evaluated. Results: The expression levels of miR-302a, miR-302b and miR-302c in GC tissues were all significantly lower than those in matched normal mucosa (all P < 0.001), but miR-302d expression had no significant differences between cancer and normal groups. Additionally, GC patients with low miR-302a, miR-302b and miR-302c expression more frequently had positive lymph node metastasis (all P < 0.05), advanced TNM stage (all P < 0.05) and great depth of invasion (all P < 0.05). More importantly, low miR-302a, miR-302b and miR-302c expression in GC tissues were significantly associated with shorter disease-free and overall survivals of GC patients (all P < 0.05). Further multivariate analysis identified miR-302a, miR-302b and miR-302c as independent prognostic markers for GC patients. Conclusions: GC patients with the decreased expression of miR-302a, miR-302b and miR-302c may had aggressive cancer progression and unfavorable prognosis. Further rigorous validation based on a large cohort of clinical cases should be performed.
C1 [Ma, Gang] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 6 Beijing Road West, 223300 Huainan, Jiangsu, China.
[Li, Qianjun] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 6 Beijing Road West, 223300 Huainan, Jiangsu, China.
[Dai, Weijie] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 6 Beijing Road West, 223300 Huainan, Jiangsu, China.
[Yang, Xiaozhong] Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 6 Beijing Road West, 223300 Huainan, Jiangsu, China.
[Sang, Aiyu] Lianshui Third People’s Hospital, Department of Internal Medicine, 12 Gaogouzhen 307 Road South, 223411 Lianshui, Jiangsu, China.
RP Yang, X (reprint author), Nanjing Medical University, Huai’an First People’s Hospital, Department of Gastroenterology, 223300 Huainan, China.
EM xzyangha@sina.com
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Chen PH, Shih CM, Chang WC, Cheng CH, Lin CW, Ho KH, Su PC, Chen KC, 2014, MicroRNA-302b-inhibited E2F3 transcription factor is related to all trans retinoic acid-induced glioma cell apoptosis. J Neurochem 131:731–742
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2017
VL 23
IS 4
BP 899
EP 905
DI 10.1007/s12253-017-0282-7
PG 7
ER
PT J
AU Zalatnai, A
Perjesi, E
Galambos, E
AF Zalatnai, Attila
Perjesi, Eszter
Galambos, Eszter
TI Much More than Trousseau Syndrome. The Broad Spectrum of the Pancreatic Paraneoplastic Syndromes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Pancreatic cancer; Paraneoplastic syndromes; Trousseau syndrome; Hypercoagulability; Venous thromboembolism; Tissue factor; De novo diabetes mellitus
ID Pancreatic cancer; Paraneoplastic syndromes; Trousseau syndrome; Hypercoagulability; Venous thromboembolism; Tissue factor; De novo diabetes mellitus
AB When 150 years ago Armand Trousseau proposed that some thrombotic events might be the first sign of concealed visceral malignancies, these findings seemed to be just of anecdotal interest. Since then, however, we have learned that adenocarcinomas, including pancreatic cancers could be associated with a wide spectrum of paraneoplastic syndromes. They may precede the detection of the tumor, may occur simultaneously or may develop during its progression. Due to various hematologic, endocrine, cutaneous, articular, neuromuscular, renal or even psychiatric syndromes, their correct interpretation is intriguing, and because their early signs are not necessarily recognized first by oncologists, the paraneoplastic syndromes pose a diagnostic challenge. Unfortunately, we cannot generalize about their mechanisms, because the molecular backgrounds are far-reaching. In most of the cases, the pancreatic cancer cells release various factors into the bloodstreamtriggering the coagulation cascade. These patients frequently present with venous thromboembolism, and sometimes they are resistant to anticoagulation. The simultaneous thrombotic and bleeding evens do reflect the abnormal hemostasis. In other instances autoantibodies are formed against cutaneous, renal, neuromuscular or nervous tissues, but the mechanism of some syndromes remains unclear. Clinicians should be aware that pancreatic carcinoma may be associated with not just the Trousseau-syndrome.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Perjesi, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Galambos, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 1
EP 10
DI 10.1007/s12253-017-0206-6
PG 10
ER
PT J
AU Min, H
Sun, X
Yang, X
Zhu, H
Liu, J
Wang, Y
Chen, G
Sun, X
AF Min, Hua
Sun, Xiangdong
Yang, Xi
Zhu, Hongcheng
Liu, Jia
Wang, Yuandong
Chen, Guangzong
Sun, Xinchen
TI Exosomes Derived from Irradiated Esophageal Carcinoma-Infiltrating T Cells Promote Metastasis by Inducing the Epithelial–Mesenchymal Transition in Esophageal Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tcells; Radiotherapy; Exosome; Esophageal carcinoma; Epithelial–mesenchymal transition; Metastasis
ID Tcells; Radiotherapy; Exosome; Esophageal carcinoma; Epithelial–mesenchymal transition; Metastasis
AB Exosomes are nanovesicles derived from tumor and normal cells that are detectable in human biological fluids, such as plasma, and cell culture supernatants. The function of exosome secretion from "normal" cells is unclear. Although numerous studies have investigated exosomes derived from hematopoietic cells, little is known regarding exosomes from T cells, even though these cells play significant roles in innate and acquired immunity. A CCK-8 assay was used to examine the ability of exosomes to inhibit TE13 cell proliferation. In vitro invasion and wound healing assays were conducted to explore the effects of exosomes on TE13 cell migration and invasion. A Western blottinganalys is was performed to investigate the effects of exosomes on the expression of the EMT-related moleculesβ-catenin, NF-κB and snail. This study aimed to investigate the effects of exosomes from irradiated T cells on the human esophageal squamous cell carcinoma (ESCC) cell line TE13 and revealed that exosomes inhibit the proliferation but promote the metastasis of TE13 cells in a dose-and time-dependent manner. Furthermore, exosomes significantly increased the expression of β-catenin, NF-κB and snail in TE13 cells. The results of this study suggest an important role for T cell-derived exosomes in the progression of esophageal carcinoma: T cell-derived exosomes promote esophageal cancer metastasis, likely by promoting the EMT through the upregulation of β-catenin and the NF-κB/snail pathway. Moreover, this study supports the use of exosomes as a nearly perfect example of biomimetic nanovesicles that could be utilized in future therapeutic strategies against various diseases, including cancer.
C1 [Min, Hua] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Sun, Xiangdong] The 81st Hospital of PLA, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Yang, Xi] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Zhu, Hongcheng] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Liu, Jia] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Wang, Yuandong] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Chen, Guangzong] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
[Sun, Xinchen] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu Province, China.
RP Sun, X (reprint author), The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, China.
EM sunxinchen2012@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 11
EP 18
DI 10.1007/s12253-016-0185-z
PG 8
ER
PT J
AU Manimaran, A
Manoharan, Sh
AF Manimaran, Asokan
Manoharan, Shanmugam
TI Tumor Preventive Efficacy of Emodin in 7,12-Dimethylbenz[a] Anthracene-Induced Oral Carcinogenesis: a Histopathological and Biochemical Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral cancer; Emodin; Lipid peroxidation; Antioxidants; Apoptosis; Detoxification agents
ID Oral cancer; Emodin; Lipid peroxidation; Antioxidants; Apoptosis; Detoxification agents
AB The aim of the present study is to focus the chemopreventive potential of Emodin during 7,12-dimethylbenz [a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Tumors were developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA thrice a week for 14 weeks. The status of lipid peroxidation, antioxidants and detoxification agents were utilized as biochemical endpoints and the expression pattern of apoptotic proteins was employed as molecular endpoints in addition to the histopathological studies, to substantiate the anticancer potential of Emodin. Hamsters treated with DMBA + Emodin revealed mild to moderate precancerous lesions such as hyperplasia and dysplasia whereas 100% tumor formation was noticed in hamsters treated with DMBA alone. Also, Emodin treatment modulated the status of lipid peroxidation, antioxidants, phase I and II detoxification agents and apoptotic proteins in favor of the inhibition/reversal/suppression of the oral tumorigenesis in DMBA treated hamsters. The present study thus concludes that the chemopreventive potential of Emodin relies on its pro-apoptotic and antioxidant efficacy during DMBA induced hamster buccal pouch carcinogenesis.
C1 [Manimaran, Asokan] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608002 Tamil Nadu, India.
[Manoharan, Shanmugam] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, Annamalai Nagar, 608002 Tamil Nadu, India.
RP Manoharan, Sh (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608002 Tamil Nadu, India.
EM sakshiman@rediffmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 19
EP 29
DI 10.1007/s12253-017-0205-7
PG 11
ER
PT J
AU Wang, N
Chen, K
Xu, J
Yuan, F
Li, H
Deng, F
Zhang, L
AF Wang, NaNa
Chen, KeYu
Xu, Jia
Yuan, Fang
Li, HongYu
Deng, FengMei
Zhang, LuShun
TI Association of CAA and TATC Insertion/Deletion Genetic Polymorphisms in RTN4 3′-UTR with Hepatocellular Carcinoma Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; RTN4; Nogo; Polymorphisms
ID Hepatocellular carcinoma; RTN4; Nogo; Polymorphisms
AB Evidence from recent researchers suggested that RTN4 is a multifunctional gene, including tumor suppression, apoptosis, vascular remodeling, and inhibition of axonal regeneration. The CAA and TATC insertion/deletion polymorphisms (CAA/TATC polymorphisms) of RTN4 3″-untranslated regions (UTRs) have been linked to cervical squamous cell carcinoma (CSCC), uterine leiomyomas (UL) and non-small cell lung cancer (NSCLC). However, the association between these two polymorphisms sites with Hepatocellular Carcinoma (HCC) risk was not carry out before. A total of 284 HCC patients and 484 control subjects were recruited for this study. The RTN4 CAA/TATC insertion/deletion genotypes were determined using polymerase chain reaction (PCR) assay. The ID/ DD genotypes of CAA were significantly associated with an increased risk of HCC compared with the II genotype (ID vs. II: OR = 1.50, 95% CI: 1.10–2.04; DD vs. II: OR = 2.00, 95%CI: 1.15–3.46). Meanwhile, the frequency of D allele of CAA was significantly related with an increased risk of HCC compared with the I allele (D vs. I: OR = 1.39, 95% CI: 1.12–1.73). The ID genotypes of TATC was significantly associated with an increased risk of HCC compared with the DD genotype (ID vs. DD: OR = 1.70, 95% CI: 1.23–2.33). The present study provided evidence that RTN4 CAA/TATC polymorphisms were associated with HCC development in Chinese Han population.
C1 [Wang, NaNa] Chengdu Medical College, School of Medical Laboratory Science, 610500 Chengdu, China.
[Chen, KeYu] Chengdu Medical College, School of Biomedical Sciences, 610500 Chengdu, China.
[Xu, Jia] Chengdu Medical College, School of Medical Laboratory Science, 610500 Chengdu, China.
[Yuan, Fang] Sichuan University, West China School of Preclinical and Forensic Medicine, Department of Immunology, 610041 Chengdu, China.
[Li, HongYu] Sichuan University, West China Hospital, Department of Pancreatic Surgery, 610041 Chengdu, China.
[Deng, FengMei] Chengdu Medical College, Department of Neurobiology, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
[Zhang, LuShun] Chengdu Medical College, Department of Neurobiology, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
RP Zhang, L (reprint author), Chengdu Medical College, Department of Neurobiology, Department of Pathology and Pathophysiology, 610500 Chengdu, China.
EM zhangls2012@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 31
EP 34
DI 10.1007/s12253-017-0204-8
PG 4
ER
PT J
AU Virga, J
Bognar, L
Hortobagyi, T
Zahuczky, G
Csosz,
Kallo, G
Toth, J
Hutoczki, G
Remenyi-Puskar, J
Steiner, L
Klekner,
AF Virga, Jozsef
Bognar, Laszlo
Hortobagyi, Tibor
Zahuczky, Gabor
Csosz, Eva
Kallo, Gergo
Toth, Judit
Hutoczki, Gabor
Remenyi-Puskar, Judit
Steiner, Laszlo
Klekner, Almos
TI Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gliomas; Tumor grade; Extracellular matrix; Invasion; Expression
ID Gliomas; Tumor grade; Extracellular matrix; Invasion; Expression
AB Peritumoral infiltration is characteristic of astrocytomas even in low-grade tumors. Tumor cells migrate to neighbouring tissue and cause recurrence. The extracellular matrix (ECM) plays a role in tumor invasion; expression levels of its components’ have been linked to tumor invasion. This study determines the mRNA and protein expression of 20 invasion-related ECM components by examining non-tumor brain; grade I-II-III astrocytoma and glioblastoma samples. Expression levels were measured by QRT-PCR and massspectroscopy. The connection between the expression pattern and tumor grade is statistically analyzed. During the analysis of data, key molecules (brevican, cadherin-12, fibronectin and integrin-β1) correlating the most with tumor grade were selected. While the mRNA level of brevican, ErbB2, fibronectin, integrin-β1 and versican discriminates low-grade from high-grade gliomas, of proteins RHAMM, integrin-α1 and MMP2 seems important. The expression pattern was found to be distinctive for tumor grade, as statistical classifiers are capable of identifying an unknown sample’s grade using them. Furthermore, normal brain and glioma expression patterns, along with low-grade astrocytoma and glioblastoma samples, differ the most. Determining the invasion-related molecules’ expression profile provides extra information regarding the tumor’s clinical behavior. Additionally, identifying molecules playing a key role in glioma invasion could uncover potential therapeutic targets in the future.
C1 [Virga, Jozsef] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Bognar, Laszlo] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hortobagyi, Tibor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Zahuczky, Gabor] UD-GenoMed Medical Genomic Technologies Ltd, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Csosz, Eva] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Kallo, Gergo] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Toth, Judit] University of Debrecen, Department of Oncology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Hutoczki, Gabor] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Remenyi-Puskar, Judit] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Steiner, Laszlo] UD-GenoMed Medical Genomic Technologies Ltd, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Klekner, Almos] University of Debrecen, Clinical Center, Department of Neurosurgery, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Klekner, (reprint author), University of Debrecen, Clinical Center, Department of Neurosurgery, 4032 Debrecen, Hungary.
EM neurosurgery.debrecen@freemail.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 35
EP 43
DI 10.1007/s12253-017-0194-6
PG 9
ER
PT J
AU Jin, M
Long, ZW
Yang, J
Lin, X
AF Jin, Mei
Long, Zi-Wen
Yang, Jing
Lin, Xiang
TI Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Insulin-like growth factor receptor 1; Cyclooxygenase 2; Ras mutation; BRAF mutation; Clinicopathological feature; Prognosis
ID Insulin-like growth factor receptor 1; Cyclooxygenase 2; Ras mutation; BRAF mutation; Clinicopathological feature; Prognosis
AB This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RTqPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and KRas in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.
C1 [Jin, Mei] Shigatse People’s Hospital, Department of Surgery, 85700 Shigatse, Tibet, China.
[Long, Zi-Wen] Fudan University, Shanghai Cancer Center, Department of Gastric Cancer Surgery, 200032 Shanghai, China.
[Yang, Jing] Shigatse People’s Hospital, Department of Surgery, 85700 Shigatse, Tibet, China.
[Lin, Xiang] Shigatse People’s Hospital, Department of Surgery, 85700 Shigatse, Tibet, China.
RP Long, ZW (reprint author), Fudan University, Shanghai Cancer Center, Department of Gastric Cancer Surgery, 200032 Shanghai, China.
EM rudolfstar@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 45
EP 57
DI 10.1007/s12253-017-0195-5
PG 13
ER
PT J
AU Eliyatkin, N
Aktas, S
Diniz, G
Ozgur, HH
Ekin, YZ
Kupelioglu, A
AF Eliyatkin, Nuket
Aktas, Safiye
Diniz, Gulden
Ozgur, Hakan Halil
Ekin, Yildirim Zubeyde
Kupelioglu, Ali
TI Expression of Stromal Caveolin- 1 May Be a Predictor for Aggressive Behaviour of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Caveolin 1; Predictive biomarker
ID Breast cancer; Caveolin 1; Predictive biomarker
AB Caveolin-1 (Cav-1) is well known as a principal scaffolding protein of caveolae which are specialized plasma membrane structures. The role of Cav-1 in tumorigenesis of breast cancers is relatively less studied. The aim of the present study is to describe the biological roles of Cav-1 in breast cancers considering its contrasting dual functions as an oncogene and as a tumor suppressor. This study included 71 females with breast cancer who had been histopathologically diagnosed in Private Gunes Pathology Laboratory between the years 2007, and 2012. The mean age is 52.48 ± 12.8 years. Patients were followed up for a mean period of 47.97 ± 20.48 months. We didn’t determine Cav-1 positive tumor cells. In 36 cases (50.7%), there were stromal expressions of Cav-1. In the statistical analysis, there was a statistically significant correlation between Cav-1 expression and ER (p = 0.033), metastasis (p = 0.005), lymphatic invasion (p = 0.000), nodal metastasis (p = 0,003), perinodal invasion (p = 0.003), metastasis (p = 0.005) and survival (p = 0.009). We found that Cav-1 expression is associated with tumor size, histological grade, lymph node involvement. Accordingly, we have suggested that Cav-1 may be a predictive biomarker for breast cancer.
C1 [Eliyatkin, Nuket] Adnan Menderes University, Medical Faculty, Pathology DepartmentAydin, Turkey.
[Aktas, Safiye] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Diniz, Gulden] Tepecik Education and Research Hospital, Pathology Department, Kibris Sehitleri Cad 51/11 Alsancak, 35220 Izmir, Turkey.
[Ozgur, Hakan Halil] Private Gunes Pathology LaboratoryIzmir, Turkey.
[Ekin, Yildirim Zubeyde] Tepecik Education and Research Hospital, Pathology Department, Kibris Sehitleri Cad 51/11 Alsancak, 35220 Izmir, Turkey.
[Kupelioglu, Ali] Private Gunes Pathology LaboratoryIzmir, Turkey.
RP Diniz, G (reprint author), Tepecik Education and Research Hospital, Pathology Department, 35220 Izmir, Turkey.
EM agdiniz@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 59
EP 65
DI 10.1007/s12253-017-0212-8
PG 7
ER
PT J
AU Chen, P
Wang, YP
Mou, Dl
Li, ZY
Qu, QM
Wang, HY
Deng, Y
Li, XF
Wang, T
Xu, XH
Zhao, G
AF Chen, Ping
Wang, Ying-Peng
Mou, Dan-lei
Li, Zheng-Yi
Qu, Qiu-Min
Wang, Hong-Yan
Deng, Yuan
Li, Xiao-Feng
Wang, Ting
Xu, Xian-Hao
Zhao, Gang
TI Pathological Findings in Myasthenia Gravis Patients with Thymic Hyperplasia and Thymoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Myasthenia gravis; Thymic hyperplasia; Thymoma; Thymectomy
ID Myasthenia gravis; Thymic hyperplasia; Thymoma; Thymectomy
AB Thymectomy is routinely carried out in patients with myasthenia gravis (MG) and thymomas. However, there is still a dispute as to whether MG patients with thymic hyperplasia should undergo thymectomy. We aimed to investigate the pathological findings in the thymus in patients with co-existing MG and thymic hyperplasia or thymomas treated with thymectomy, as well as effects of immunosuppression. Thirty-three patients with MG were selected and grouped accordingly: patients with no thymic abnormalities, patients with thymic hyperplasia, and patients with thymomas. All patients were treated with methylprednisolone alongside immunosuppression. A separate cohort of 24 MG patients with thymic hyperplasia or thymomas and treated with thymectomy were selected. As controls, 5 patients with thymomas or thymic carcinoma without MG were selected. Expression of CD5, extracellular regulated protein kinases1/2 mitogen activated protein kinase (ERK1/2MAPKs) and CD95 ligand (FasL) in the thymus was examined. Methylprednisolone and immunosuppressive therapy are highly effective in MG patients with normal thymus tissue and MG patients with thymic hyperplasia compared to MG patients with thymomas alone. CD5 expression was highest in MG patients with thymic hyperplasia, correlating with expression of ERK1/2MAPKs. FasL expression was similar across all groups. Thymomas may be distinguished from thymic hyperplasia by expression of CD5 and ERK1/2MAPKs. Thymectomy is the preferred treatment for MG patients with thymomas but may not be necessary in MG patients with thymic hyperplasia who are treated with immunosuppressive therapy.
C1 [Chen, Ping] Fourth Military Medical University, Xijing Hospital, Department of Neurology, No. 169, Changle West Road, 710032 Xi’an, China.
[Wang, Ying-Peng] Beijing Aerospace General Hospital, Department of Neurology, 100076 Beijing, China.
[Mou, Dan-lei] Capital Medical University, Beijing You’an Hospital, Department of Infectious disease, 100075 Beijing, China.
[Li, Zheng-Yi] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Neurology, 710061 Xi’an, China.
[Qu, Qiu-Min] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Neurology, 710061 Xi’an, China.
[Wang, Hong-Yan] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Deng, Yuan] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Li, Xiao-Feng] Xi’an Jiao Tong University, First Affiliated Hospital of Medical College, Department of Pathology, 710061 Xi’an, China.
[Wang, Ting] Fourth Military Medical University, Xijing Hospital, Department of Neurology, No. 169, Changle West Road, 710032 Xi’an, China.
[Xu, Xian-Hao] Federal Ministry of Health, Beijing Hospital, Department of Neurology, No. 1, Dahua Road, 100730 Beijing, China.
[Zhao, Gang] Fourth Military Medical University, Xijing Hospital, Department of Neurology, No. 169, Changle West Road, 710032 Xi’an, China.
RP Zhao, G (reprint author), Fourth Military Medical University, Xijing Hospital, Department of Neurology, 710032 Xi’an, China.
EM zhaogang@fmmu.edu.cn
CR Vincent A, 2002, Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol 2(10):797–804
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 67
EP 74
DI 10.1007/s12253-017-0213-7
PG 8
ER
PT J
AU He, T
Guo, J
Song, H
Zhu, H
Di, X
Min, H
Wang, Y
Chen, G
Dai, W
Ma, J
Sun, X
Ma, J
AF He, Tianli
Guo, Jiayou
Song, Hongmei
Zhu, Hongcheng
Di, Xiaoke
Min, Hua
Wang, Yuandong
Chen, Guangzong
Dai, Wangshu
Ma, Jianhua
Sun, Xinchen
Ma, Jianxin
TI Nutlin-3, an Antagonist of MDM2, Enhances the Radiosensitivity of Esophageal Squamous Cancer with Wild-Type p53
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cancer; MDM2; Radiotherapy; Nutlin-3; p53
ID Esophageal squamous cancer; MDM2; Radiotherapy; Nutlin-3; p53
AB Murine double minute 2 (MDM2) negatively regulates the activity of the p53 protein and plays a vital role in cell cycle arrest, apoptosis, and senescence mediated by p53. Nutlin-3, an antagonist of MDM2, is frequently used in anticancer studies. In many human tumors, nutlin-3 stabilizes p53 status and enhances p53 expression in cells with wild-type p53. However, the effect of nutlin-3 combined with radiotherapy on esophageal squamous cancer (ESCC) has not been reported. In this study, we examined whether nutlin-3 increases the radiosensitivity of ESCC in vitro and in vivo. We chose two cell lines, ECA-109 (wild-type p53) and TE- 13 (p53 mutated), for the following experiments. Cell proliferation and clonogenic survival experiments showed that nutlin-3 inhibits the cell growth and colony formation of ECA-109 cells in a dose-dependent manner. Flow cytometry analysis showed that the apoptosis rate of ECA-109 cells cotreated with nutlin-3 and irradiation(IR) was significantly increased compared with cells treated with irradiation or nutlin- 3 alone.Western blotting detected the expression of apoptosisassociated proteins in ECA-109 cells in response to nutlin-3 and irradiation. These effects were not evident in TE-13 cells. Xenograft mouse models indicated that nutlin-3 suppresses tumor growth and promotes radiosensitivity in the ESCC cell line ECA-109 in vivo. We have demonstrated that cotreatment of nutlin-3 with irradiation can significantly inhibit the growth and improve the radiosensitivity of ESCC cells with wild-type p53. The study suggests that nutlin-3 may be a potent therapeutic agent in conjunction with radiotherapy in ESCC.
C1 [He, Tianli] Lianyungang Hospital Affiliated to Bengbu Medical College, The Second People’s Hospital of Lian Yungang, Department of radiotherapy, 161 Xingfu Road, 222000 Lian Yungang, Jiangsu Province, China.
[Guo, Jiayou] The Dongfang Hospital of Lian Yungang, Department of radiotherapy, 57 Zhonghua West Road, 222000 Lian Yungang, Jiangsu Province, China.
[Song, Hongmei] Taian City Central Hospital, 29 Longtan Road, 271000 Taian, Shandong Province, China.
[Zhu, Hongcheng] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Di, Xiaoke] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Min, Hua] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Wang, Yuandong] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Chen, Guangzong] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Dai, Wangshu] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Ma, Jianhua] Lianyungang Hospital Affiliated to Bengbu Medical College, The Second People’s Hospital of Lian Yungang, Department of radiotherapy, 161 Xingfu Road, 222000 Lian Yungang, Jiangsu Province, China.
[Sun, Xinchen] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, China.
[Ma, Jianxin] The Dongfang Hospital of Lian Yungang, Department of radiotherapy, 57 Zhonghua West Road, 222000 Lian Yungang, Jiangsu Province, China.
RP Ma, J (reprint author), The Dongfang Hospital of Lian Yungang, Department of radiotherapy, 222000 Lian Yungang, China.
EM mjx3416@163.com
CR Yang X, Yang B, Cai J, Zhang C, Zhang Q, Xu L et al, 2013, Berberine enhances radiosensitivity of esophageal squamous cancer by targeting hif-1α in vitro and in vivo. Cancer Biol Ther 14(11):1068–1073
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 75
EP 81
DI 10.1007/s12253-017-0215-5
PG 7
ER
PT J
AU Kiraly, PA
Kallay, K
Gango, A
Kellner,
Egyed, M
Szoke, A
Kiss, R
Valyi-Nagy, I
Csomor, J
Matolcsy, A
Bodor, Cs
AF Kiraly, Peter Attila
Kallay, Krisztian
Gango, Ambrus
Kellner, Adam
Egyed, Miklos
Szoke, Anita
Kiss, Richard
Valyi-Nagy, Istvan
Csomor, Judit
Matolcsy, Andras
Bodor, Csaba
TI Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Familial MDS/AML; Genetic predisposition; Germline mutation
ID Familial MDS/AML; Genetic predisposition; Germline mutation
AB Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification. According to the new classification, these disorders are subdivided based on the clinical and genetic features, including myeloid neoplasms with germline predisposition alone, or with pre-existing platelet disorder, cytopaenias or other organ failures. The predisposing genetic factors include mutations in the RUNX1, CEBPA, GATA2, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 genes. The genes affected in these syndromes are important regulators of haemopoiesis and are frequently implicated in leukaemogenesis, providing deeper insight into the understanding of normal and malignant haemopoiesis. Despite the growing knowledge of germline predisposing events in the background of familial myeloid malignancies, the germline genetic component is still unknown in a subset of these pedigrees. Here, we present the first study of inherited myeloid malignancies in Hungary.We identified three families with apparent clustering of myeloid malignancies with nine affected individuals across these pedigrees. All tested individuals were negative for CEBPA, GATA2, RUNX1, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 mutations, suggesting the presence of so far unidentified predisposing mutations.
C1 [Kiraly, Peter Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kallay, Krisztian] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Gango, Ambrus] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kellner, Adam] Kaposi Mor Teaching Hospital, Department of HematologyKaposvar, Hungary.
[Egyed, Miklos] Kaposi Mor Teaching Hospital, Department of HematologyKaposvar, Hungary.
[Szoke, Anita] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Kiss, Richard] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Valyi-Nagy, Istvan] Del-Pesti CentrumkorhazBudapest, Hungary.
[Csomor, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Bodor, Cs (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM bodor.csaba1@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 83
EP 88
DI 10.1007/s12253-017-0216-4
PG 6
ER
PT J
AU Golan, Sh
Gerber, G
Margel, D
Rath-Wolfson, L
Ehrlich, Y
Koren, R
Lifshitz, D
AF Golan, Shay
Gerber, Glenn
Margel, David
Rath-Wolfson, Lea
Ehrlich, Yaron
Koren, Rumelia
Lifshitz, David
TI A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Upper urinary tract urothelial carcinoma; Ureteroscopy; Biopsy; Pathology
ID Upper urinary tract urothelial carcinoma; Ureteroscopy; Biopsy; Pathology
AB To examine the ability of a new specimen handling technique to improve histopathological yield of ureteroscopic biopsies, performed in patients with suspected upper tract urothelial carcinoma (UTUC). In a bi-center retrospective study we compared the results of the new tissue handling technique (group 1) with the standard technique (group 2). In the new technique, to achieve maximal tissue preservation, the specimen is mounted on filter paper prior to embedding in paraffin. Multivariate analysis was performed to determine which factors are associated with optimal histological results. We further compared the biopsies with the final specimen in a subgroup of patients who underwent nephroureterectomy (NU). Of 55 ureteroscopic biopsies, 1 biopsy from group 1 (new technique) and 3 biopsies from group 2 (standard technique) were inadequate for pathological examination. 51 UTUC specimens were analyzed. Tumor grade and stage were determined in 85% and 63% of the patients in group 1 and in 83% and 25% of group 2 (p=0.85 and p=0.007). Orientation was preserved in 82% of group 1 and 42% of group 2 (p=0.003). On multivariate analysis biopsy technique and biopsy diameter were found to predict stage determination (p=0.01 and p=0.007) and tissue orientation (p=0.005 and p=0.04). Among patients who underwent NU, stage concordance between the biopsy and final pathology was observed in 56% and 27% of the patients in group 1 and 2, respectively. The new processing technique for small UTUC forceps biopsies decreases the rate of biopsies with insufficient material and improves biopsy interpretation.
C1 [Golan, Shay] University of Chicago Medicine, Department of Surgery, 5841 S. Maryland Ave, 60637 Chicago, IL, USA.
[Gerber, Glenn] University of Chicago Medicine, Department of Surgery, 5841 S. Maryland Ave, 60637 Chicago, IL, USA.
[Margel, David] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
[Rath-Wolfson, Lea] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Ehrlich, Yaron] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
[Koren, Rumelia] Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Department of PathologyTel Aviv, Israel.
[Lifshitz, David] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
RP Golan, Sh (reprint author), University of Chicago Medicine, Department of Surgery, 60637 Chicago, USA.
EM shaygo1@gmail.com
CR Siegel R, Naishadham D, Jemal A, 2012, Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29
Golan S, Nadu A, Lifshitz D, 2015, The role of diagnostic ureteroscopy in the era of computed tomography urography. BMC Urol 15:74
Roupret M et al, 2013, European guidelines on upper tract urothelial carcinomas: 2013 update. Eur Urol 63(6):1059–1071
Cutress ML et al, 2012, Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience. BJU Int 110(11):1608–1617
Gadzinski AJ et al, 2010, Long-term outcomes of nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma. J Urol 183(6):2148–2153
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 89
EP 94
DI 10.1007/s12253-017-0219-1
PG 6
ER
PT J
AU Uson, LSP
Filho, CD
Bugano, DGD
Geyer, CF
de Nigro Corpa, VM
Goncalves, DSP
Simon, DS
Kaliks, AR
AF Uson, Luiz Serrano Pedro
Filho, Callegaro Donato
Bugano, Diniz Gomes Diogo
Geyer, Correa Felipe
de Nigro Corpa, Vinicius Marcus
Goncalves, David Scatena Paulo
Simon, Daniel Sergio
Kaliks, Aliosha Rafael
TI Incidental Findings in Reduction Mammoplasty Specimens in Patients with No Prior History of Breast Cancer. An Analysis of 783 Specimens
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Mammoplasty; Breast reduction surgery; Incidental findings
ID Breast cancer; Mammoplasty; Breast reduction surgery; Incidental findings
AB Breast reduction surgery is a common procedure and the rate of incidental findings in the removed specimens varies between 0% and 4.6%. There are no guidelines about pathological evaluation of breast reduction surgery. We reviewed all pathology reports of patients undergoing breast reduction surgery in a single tertiary institution in Brazil from January 2008 to August 2014. Exclusion criteria were a personal history of breast cancer, unclear reason for mastectomy and incomplete data on the pathology report. We considered "relevant findings" flat epithelial atypia, atypical hyperplasia, carcinomas in situ and invasive carcinoma. Of 1672 specimens from breast reduction surgery, 783 met inclusion criteria. Median patient age was 40 (8–77), 91% underwent bilateral mastectomy and 57% of the specimens weighted less than 200 g. In 55% of cases, 4 or more paraffin blocks were sampled. There were 40 (5.1%) relevant findings and the most common was atypical lobular hyperplasia (16–2%). There were 3 invasive carcinomas (0.38%). In multivariate analysis, the only variables associated with a higher odds of relevant pathological findings were patient age ≥ 40 (OR 4.73 CI95% 1.98–11.3 p < 0.001) and sampling of ≥4 paraffin blocks from each specimen (OR 6.69 95% CI 2.25–19.9 p < 0.001). The incidence of pre-malignant and malignant lesions in specimens from breast reduction surgery is around 5%, but this risk is significantly higher for patients older than 40 years-old. Sampling at least 4 paraffin blocks from each specimen significantly increases detection rates.
C1 [Uson, Luiz Serrano Pedro] Hospital Israelita Albert Einstein, Oncology Department, 627/701 Av. Albert Einstein, 05651-901 Sao Paulo, CEP, Brazil.
[Filho, Callegaro Donato] Hospital Israelita Albert Einstein, Oncology Department, 627/701 Av. Albert Einstein, 05651-901 Sao Paulo, CEP, Brazil.
[Bugano, Diniz Gomes Diogo] Hospital Israelita Albert Einstein, Oncology Department, 627/701 Av. Albert Einstein, 05651-901 Sao Paulo, CEP, Brazil.
[Geyer, Correa Felipe] Hospital Israelita Albert Einstein, Pathology DepartmentSao Paulo, Brazil.
[de Nigro Corpa, Vinicius Marcus] Hospital Israelita Albert Einstein, Pathology DepartmentSao Paulo, Brazil.
[Goncalves, David Scatena Paulo] Hospital Israelita Albert Einstein, Epidemiology DepartmentSao Paulo, Brazil.
[Simon, Daniel Sergio] Hospital Israelita Albert Einstein, Oncology Department, 627/701 Av. Albert Einstein, 05651-901 Sao Paulo, CEP, Brazil.
[Kaliks, Aliosha Rafael] Hospital Israelita Albert Einstein, Oncology Department, 627/701 Av. Albert Einstein, 05651-901 Sao Paulo, CEP, Brazil.
RP Uson, LSP (reprint author), Hospital Israelita Albert Einstein, Oncology Department, 05651-901 Sao Paulo, Brazil.
EM pedroluiz_uson@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 95
EP 99
DI 10.1007/s12253-017-0230-6
PG 5
ER
PT J
AU Zou, Yh
Li, Xd
Zhang, Qh
Liu, Dz
AF Zou, Yuan-hang
Li, Xue-dong
Zhang, Qi-hao
Liu, De-zhong
TI RACK1 Silencing Induces Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma MHCC97-H Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RACK1; Hepatocellular carcinoma; Cell proliferation; Cell apoptosis; Gene silencing; MHCC97-H
ID RACK1; Hepatocellular carcinoma; Cell proliferation; Cell apoptosis; Gene silencing; MHCC97-H
AB This study aimed to explore the effects of RACK1 gene silencing on the apoptosis and proliferation of hepatocellular carcinoma (HCC) MHCC97-H cells. After transfecting MHCC97-H cells with siRNA, RACK1 gene silencing model was established. The cells were divided into blank group, siRNA group and empty plasmid group, respectively. The mRNA and protein expressions of RACK1, cyclin D1 and BAX were determined by qRT-PCR and Western blotting. CCK-8 assay, flow cytometry and FITC-Annexin V/PI staining were used to determine cell viability, cell cycle and cell apoptosis, respectively. The results of qRT-PCR and Western blotting suggested that when compared with the blank group and the empty plasmid group, the mRNA and protein expressions of RACK1 and Cyclin D1 decreased significantly while the mRNA and protein BAX expressions increased substantially in the siRNA group (all P < 0.05). The results of CCK-8 assay revealed that the siRNA group exhibited significantly lower cell viability when compared with the blank group and the empty plasmid group (both P < 0.05); and the cell viability in the siRNA group decreased gradually with the increase of time. The results of flow cytometry and FITC-Annexin V/PI staining indicated that when compared with the blank group and the empty plasmid group, the proportion of cells in S phase was markedly lower and the apoptosis rate was significantly higher in the siRNA group (both P < 0.05). Our study suggests that inhibition of RACK1 could suppress cell proliferation and induce apoptosis in HCC MHCC97-H cells.
C1 [Zou, Yuan-hang] The First Affiliated Hospital of Shantou University Medical College, Department of Hepatobiliary Surgery, No. 57, Changping Road, 515041 Shantou, Guangdong Province, China.
[Li, Xue-dong] The First Affiliated Hospital of Shantou University Medical College, Department of Orthopedics, No. 57, Changping Road, 515041 Shantou, Guangdong Province, China.
[Zhang, Qi-hao] The First Affiliated Hospital of Shantou University Medical College, Department of Orthopedics, No. 57, Changping Road, 515041 Shantou, Guangdong Province, China.
[Liu, De-zhong] The First Affiliated Hospital of Shantou University Medical College, Department of Emergency Surgery, No. 57, Changping Road, 515041 Shantou, Guangdong Province, China.
RP Liu, Dz (reprint author), The First Affiliated Hospital of Shantou University Medical College, Department of Emergency Surgery, 515041 Shantou, China.
EM cowboyzhong@163.com
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(2015, Inhibition of Notch- and EGFR signaling reduces cell viability and angiogenesis in glioblastoma multiforme. Journal/Cancer Research 75: 1369–1369.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 101
EP 107
DI 10.1007/s12253-017-0214-6
PG 7
ER
PT J
AU Zhang, J
Zhao, B
Chen, X
Wang, Z
Xu, H
Huang, B
AF Zhang, Jiale
Zhao, Bochao
Chen, Xiuxiu
Wang, Zhenning
Xu, Huimian
Huang, Baojun
TI Silence of Long Noncoding RNA NEAT1 Inhibits Malignant Biological Behaviors and Chemotherapy Resistance in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Long noncoding RNA; NEAT1; Gastric cancer; Malignant behaviors; Chemotherapy resistance
ID Long noncoding RNA; NEAT1; Gastric cancer; Malignant behaviors; Chemotherapy resistance
AB Gastric cancer (GC) is the most common solid tumor in digestive system. Nuclear-enriched abundant transcript 1 (NEAT1) gene is a lncRNA, and reveal potential oncogene role in several malignant tumors. The aim of this study is to investigate the expression and clinical significance of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) gene and its influence to malignant biologic behaviors and chemotherapy resistance to adriamycin in GC. This study found NEAT1 was up-regulated in GC tissues and cells, especially in in GC adriamycin-resistant cells. NEAT1 silence in SGC7901 cells could inhibit proliferation and invasion ability, and promote cell apoptosis significantly. NEAT1 silence in adriamycin-resistant SGC7901/ADR cells also depressed the half maximal inhibitory concentration (IC50) for adriamycin, chemotherapy resistance to adriamycin was inhibited significantly. NEAT1 knockdown promoted apoptosis in SGC7901/ ADR cells induced by adriamycin. In summary, lncRNA NEAT1 is high-expressed in GC and functions as an oncogene to modulate apoptosis, invasion, proliferation and chemotherapy resistance of GC cells, which might be a novel potential therapeutic target for GC.
C1 [Zhang, Jiale] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
[Zhao, Bochao] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
[Chen, Xiuxiu] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
[Wang, Zhenning] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
[Xu, Huimian] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
[Huang, Baojun] China Medical University, Affiliated First Hospital, Department of Surgical Oncology, No.155 Nanjing North Street, Heping District, 110001 Shenyang, Liaoning, China.
RP Huang, B (reprint author), China Medical University, Affiliated First Hospital, Department of Surgical Oncology, 110001 Shenyang, China.
EM huang_bj@163.com
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Adriaens C, Standaert L, Barra J, Latil M, Verfaillie A, Kalev P, Boeckx B, Wijnhoven PW, Radaelli E, Vermi W, Leucci E, Lapouge G, Beck B, van den Oord J, Nakagawa S, Hirose T, Sablina AA, Lambrechts D, Aerts S, Blanpain C, Marine JC, 2016, p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat Med 22(8):861–868
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Jiang P, Wu X, Wang X, Huang W, Feng Q, 2016, NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells. Oncotarget., DOI 10.18632/oncotarget.9712
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 109
EP 113
DI 10.1007/s12253-017-0233-3
PG 5
ER
PT J
AU Acs, B
Madaras, L
Kovacs, AK
Micsik, T
Tokes, AM
Gyorffy, B
Kulka, J
Szasz, MA
AF Acs, Balazs
Madaras, Lilla
Kovacs, Attila Kristof
Micsik, Tamas
Tokes, Anna-Maria
Gyorffy, Balazs
Kulka, Janina
Szasz, Marcell Attila
TI Reproducibility and Prognostic Potential of Ki-67 Proliferation Index when Comparing Digital-Image Analysis with Standard Semi-Quantitative Evaluation in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ki-67 proliferation index; Breast cancer; Digital image analysis; Intra-class correlation; Concordance correlation; Prognosis
ID Ki-67 proliferation index; Breast cancer; Digital image analysis; Intra-class correlation; Concordance correlation; Prognosis
AB In this study, the reproducibility of Ki-67 proliferation index (KIPI) was investigated by comparing the semiquantitative (SQ) results of three assessors with those of digital image-analysis (DIA) methods. The prognostic significance of the two approaches was also correlated with clinical outcome. Tissue microarrays of duplicate 2 mm cores were constructed from representative areas of formalin-fixed and paraffin-embedded tumor blocks of 347 breast cancer patients. SQ evaluation of Ki-67 (MIB1 clone) immunostained slides was performed independently by three pathologists. DIA was completed using a fully automated histological pattern and cell recognition module for KIPI detection (DIA-1) and an adjustable module (DIA-2) with the possibility of manual corrections. To compare SQ and DIA evaluations intra-class correlation (ICC) and concordance correlation coefficients (CCC) were determined. The three SQ evaluations demonstrated a remarkable ICC (0.853). Significant difference and poor concordance occurred between SQ-1 and SQ-2 as well as between SQ-1 and SQ-3 (p ≤ 0.001, CCC ≤ 0.827 for both comparisons). Thus, the reference KIPI value (SQ-RV) was generated from the mean values of SQ-2 and SQ-3. SQ-RV and DIA-2 results showed substantial concordance (CCC = 0.963, at p = 0.754), while SQ-RV and DIA-1 values differed (p ≤ 0.001) at only moderate concordance (CCC = 0.906). In multivariate analysis, lymph node status and SQ-2 assessment were significantly associated with clinical outcome (p ≤ 0.012 for both comparisons). Our results confirm that KIPI is a significant prognostic marker in breast cancer, which can be can be reliably reproduced by using an adjustable DIA-2 image analysis module.
C1 [Acs, Balazs] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Madaras, Lilla] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Kovacs, Attila Kristof] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 26 Ulloi ut, 1085 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Gyorffy, Balazs] MTA TTK, Lendulet Cancer Biomarker Research Group, 2 Magyar tudosok korutja, 1117 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
[Szasz, Marcell Attila] Semmelweis University, 2nd Department of Pathology, 93 Ulloi ut, 1091 Budapest, Hungary.
RP Szasz, MA (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM cac@korb2.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 115
EP 127
DI 10.1007/s12253-017-0220-8
PG 13
ER
PT J
AU Rong, L
Huang, W
Tian, Sh
Chi, X
Zhao, P
Liu, F
AF Rong, Li
Huang, Wei
Tian, Shangkun
Chi, Xiangbo
Zhao, Pan
Liu, Fengfeng
TI COL1A2 is a Novel Biomarker to Improve Clinical Prediction in Human Gastric Cancer: Integrating Bioinformatics and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; biomarker; bioinformatics; COL1A2
ID gastric cancer; biomarker; bioinformatics; COL1A2
AB Gastric cancer is the third most common cause of cancer-related death in worldwide. It is crucial to target the key genes controlling pathogenesis in the early stage of gastric cancer. This study describes an integrated bioinformatics to identify molecular biomarkers for gastric cancer in patients’ cancer tissues. We reports differently expression genes in large gastric cancer cohorts from Gene Expression Ominus (GEO). Our findings revealed that 433 genes were significantly different expressed in human gastric cancer. Differently expression gene profile in gastric cancer was further validated by bioinformatic analyses, co-expression network construction. Based on the co-expression network and top-ranked genes, we identified collagen type I alpha 2 (COL1A2) which encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain, was the key gene in a 37-gene network that modulates cell motility by interacting with the cytoskeleton. Furthermore, the prognostic role of COL1A2 was determined by use of immunohistochemistry on human gastric cancer tissue. COL1A2 was highly expressed in human gastric cancer as compared with normal gastric tissues. Statistical analysis showed COL1A2 expression level was significantly associated with histological type and lymph node status. However, there were no correlations between COL1A2 expression and age, lymph node numbers, tumor size, or clinical stage. In conclusion, the novel bioinformatics used in this study has led to identification of improving diagnostic biomarkers for human gastric cancer and could benefit further analyses of the key alteration during its progression.
C1 [Rong, Li] Chongqing Infectious Disease Medical Center, Department of gastroenterology, 1#Huangjuewan, Xiaolongkan, Shapingba District, 400030 Chongqing, China.
[Huang, Wei] Southwest University of Political Science and Law, Health Center, 401120 Chongqing, China.
[Tian, Shangkun] Chongqing Infectious Disease Medical Center, Department of gastroenterology, 1#Huangjuewan, Xiaolongkan, Shapingba District, 400030 Chongqing, China.
[Chi, Xiangbo] Chongqing Infectious Disease Medical Center, Department of gastroenterology, 1#Huangjuewan, Xiaolongkan, Shapingba District, 400030 Chongqing, China.
[Zhao, Pan] Chongqing Infectious Disease Medical Center, Department of gastroenterology, 1#Huangjuewan, Xiaolongkan, Shapingba District, 400030 Chongqing, China.
[Liu, Fengfeng] Chongqing Infectious Disease Medical Center, Department of gastroenterology, 1#Huangjuewan, Xiaolongkan, Shapingba District, 400030 Chongqing, China.
RP Rong, L (reprint author), Chongqing Infectious Disease Medical Center, Department of gastroenterology, 400030 Chongqing, China.
EM lirongcq@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 129
EP 134
DI 10.1007/s12253-017-0223-5
PG 6
ER
PT J
AU Brzozowska, A
Powrozek, T
Homa-Mlak, I
Mlak, R
Ciesielka, M
Golebiowski, P
Malecka-Massalska, T
AF Brzozowska, Anna
Powrozek, Tomasz
Homa-Mlak, Iwona
Mlak, Radoslaw
Ciesielka, Marzanna
Golebiowski, Pawel
Malecka-Massalska, Teresa
TI Polymorphism of Promoter Region of TNFRSF1A Gene (−610 T > G) as a Novel Predictive Factor for Radiotherapy Induced Oral Mucositis in HNC Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral mucositis; Radiotherapy; Head and neck cancer; Polymorphism; TNFRSF1A
ID Oral mucositis; Radiotherapy; Head and neck cancer; Polymorphism; TNFRSF1A
AB Every year, about 650 thousand new cases of Head and Neck Cancer (HNC) are diagnosed globally. Apart from surgery, radiotherapy (RTH), chemotherapy (CHT) or its combination is used in the treatment of HNC. One of the most frequent complications and, at the same time, limitations of RTH is oral mucositis (OM). Proinflammatory cytokines (including TNF-α) play a key role in the development of OM. Genetic alterations, i.e. single nucleotide polymorphisms (SNPs) within genes encoding for receptors for TNF (ie. TNFRSF1A) may change their function. The aim of this study was to investigate relationship between a polymorphism of TNFRSF1A and occurrence and severity of acute reaction after RTH for HNC patients. Data from 58 HNC patients (stages I-IV) were analyzed. All of them were irradiated using IMRT technique with doses 50-70Gy. Oral mucositis (OM)was evaluated according to RTOG/EORTC guidelines. DNA from HNC patients were isolated from whole blood and genotypes were determined by sequencing method. Patients with TT or GT genotype demonstrated higher risk of manifestation of grade 3 OM in 5th week of RTH (p=0.041; OR=9.240; 95% CI: 1.101–77.581) compared to GG carriers. Similarly, high risk of grade 3 OM in patients with T allele presence was noted in 6th week (p=0.030; OR=10.50; 95%CI:1.257–87.690) and in 7th week (p=0.008; OR=5.625; 95% CI: 1.584–19.975) of treatment compared to patients with GG homozygote. Our results indicate an association between SNP of TNFRSF1A (rs4149570) gene and risk of more severe OM related to radiation therapy for HNC patients.
C1 [Brzozowska, Anna] Medical University of Lublin, Department of Oncology, Jaczewskiego 7, 20-090 Lublin, Poland.
[Powrozek, Tomasz] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Homa-Mlak, Iwona] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Mlak, Radoslaw] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Ciesielka, Marzanna] Medical University of Lublin, Department of Forensic Medicine, Jaczewskiego 8, 20-090 Lublin, Poland.
[Golebiowski, Pawel] Medical University of Lublin, Department of Oncology, Jaczewskiego 7, 20-090 Lublin, Poland.
[Malecka-Massalska, Teresa] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
RP Brzozowska, A (reprint author), Medical University of Lublin, Department of Oncology, 20-090 Lublin, Poland.
EM annabrzo@poczta.onet.pl
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 135
EP 143
DI 10.1007/s12253-017-0227-1
PG 9
ER
PT J
AU Heydari, K
Saidijam, M
Sharifi, RM
Dermani, KF
Asl, SS
Shabab, N
Najafi, R
AF Heydari, Korosh
Saidijam, Massoud
Sharifi, Reza Mohammad
Dermani, Karimi Fatemeh
Asl, Soleimani Sara
Shabab, Nooshin
Najafi, Rezvan
TI The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; miR-200c; 5-FU resistance; E-cadherin; PTEN
ID Colorectal cancer; miR-200c; 5-FU resistance; E-cadherin; PTEN
AB 5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR- 200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT- 116 cells to 5-FU. HCT-116 cells were transfected with LNA anti-miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.
C1 [Heydari, Korosh] Hamadan University of Medical Sciences, Research Center for Molecular MedicineHamadan, Iran.
[Saidijam, Massoud] Hamadan University of Medical Sciences, Research Center for Molecular MedicineHamadan, Iran.
[Sharifi, Reza Mohammad] Isfahan University of Medical Sciences, School of Medicine, Department of Genetics and Molecular BiologyIsfahan, Iran.
[Dermani, Karimi Fatemeh] Hamadan University of Medical Sciences, Research Center for Molecular MedicineHamadan, Iran.
[Asl, Soleimani Sara] Hamadan University of Medical Sciences, Faculty of Medicine, Department of AnatomyHamadan, Iran.
[Shabab, Nooshin] Hamadan University of Medical Sciences, Research Center for Molecular MedicineHamadan, Iran.
[Najafi, Rezvan] Hamadan University of Medical Sciences, Research Center for Molecular MedicineHamadan, Iran.
RP Najafi, R (reprint author), Hamadan University of Medical Sciences, Research Center for Molecular Medicine, Hamadan, Iran.
EM re.najafi@umsha.ac.ir;najafi2535@gmail.com
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Gotanda K, Hirota T, Matsumoto N, Ieiri I, 2013, MicroRNA-433 negatively regulates the expression of thymidylate synthase, TYMS, responsible for 5-fluorouracil sensitivity in HeLa cells. BMC Cancer 13(1):369
Hewish M, Lord CJ, Martin SA, Cunningham D, Ashworth A, 2010, Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol 7(4):197–208
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Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L et al, 2008, The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14(11):1271–1277
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 145
EP 151
DI 10.1007/s12253-017-0222-6
PG 7
ER
PT J
AU Murugan, P
Rao, P
Tamboli, P
Czerniak, B
Guo, CCh
AF Murugan, Paari
Rao, Priya
Tamboli, Pheroze
Czerniak, Bogdan
Guo, C Charles
TI Primary Ewing Sarcoma / Primitive Neuroectodermal Tumor of the Kidney: A Clinicopathologic Study of 23 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kidney; Ewing sarcoma; Histology; Immunohistochemistry; Cytogenetics; Clinical outcome
ID Kidney; Ewing sarcoma; Histology; Immunohistochemistry; Cytogenetics; Clinical outcome
AB Primary Ewing sarcoma / primitive neuroec todermal tumor (ES) of the kidney is a rare neoplasm with limited clinicopathologic data. We report 23 such cases with no history of ES elsewhere in the body. The patients included 13 male and 10 female, aged 8–70 years (mean, 31 years). The average tumor size was 11.7 cm (range, 5–20 cm). Microscopic analysis showed predominantly lobular growth (n = 14), with focal papillary (n = 3), alveolar (n = 1), and hemangiopericytoma-like (n = 1) patterns. Several tumors (n = 11) exhibited robust mitotic activity (>10 mitoses/10 high-power fields). Necrosis (n = 13) and lymphovascular invasion (n = 14) were common. Homer Wright rosettes (n = 6) and perivascular pseudorosettes (n = 1) were also identified. The tumors invaded the renal sinus or perinephric fat (n = 11), renal vein (n = 13), and adrenal gland (n = 2). Molecular and fluorescence in situ hybridization analysis showed rearrangement of EWSR1 gene (10/10), associated with EWSR1-FLI1 gene fusion (7/10). All patients with follow-up information (n = 18) had metastasis, commonly in the lungs (n = 12) and bone (n = 6). Twelve patients died of disease in a mean of 21 months; 6 patients were alive at a mean of 49 months after diagnosis. Primary kidney ES usually present at an advanced stage with extrarenal spread and metastasis. Although renal ES share histologic, immunohistochemical, and molecular features with their bone and soft tissue counterparts, they appear to be more aggressive tumors with poorer clinical outcome.
C1 [Murugan, Paari] University of Minnesota, Department of Laboratory Medicine and PathologyMinneapolis, MN, USA.
[Rao, Priya] The University of Texas, MD Anderson Cancer CenterHouston, TX, USA.
[Tamboli, Pheroze] The University of Texas, MD Anderson Cancer CenterHouston, TX, USA.
[Czerniak, Bogdan] The University of Texas, MD Anderson Cancer CenterHouston, TX, USA.
[Guo, C Charles] The University of Texas, MD Anderson Cancer CenterHouston, TX, USA.
RP Murugan, P (reprint author), University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis, USA.
CR Ewing J, 1921, Diffuse endothelioma of bone. Proc NY Pathol Soc 21:17–24
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Mor Y, Nass D, Raviv G, Neumann Y, Nativ O, Goldwasser B, 1994, Malignant peripheral primitive neuroectodermal tumor, PNET, of the kidney. Med Pediatr Oncol 23:437–440
Rowe RG, Thomas DG, Schuetze SM, Hafez KS, Lawlor ER, Chugh R, 2013, Ewing sarcoma of the kidney: case series and literature review of an often overlooked entity in the diagnosis of primary renal tumors. Urology 81(2):347–353
Parham DM, Roloson GJ, Feely M, Green DM, Bridge JA, Beckwith JB, 2001, Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms tumor study group pathology Center. Am J Surg Pathol 25(2):133–146
Toomey EC, Schiffman JD, Lessnick SL, 2010, Recent advances in the molecular pathogenesis of Ewing's sarcoma. Oncogene 29(32): 4504–4516
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Luo W, Gangwal K, Sankar S, Boucher KM, Thomas D, Lessnick SL, 2009, GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewings sarcoma oncogenesis and therapeutic resistance. Oncogene 28(46):4126–4132
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 153
EP 159
DI 10.1007/s12253-017-0228-0
PG 7
ER
PT J
AU Roncati, L
Gatti, MA
Barbolini, G
Piscioli, F
Pusiol, T
Maiorana, A
AF Roncati, Luca
Gatti, Morena Antonietta
Barbolini, Giuseppe
Piscioli, Francesco
Pusiol, Teresa
Maiorana, Antonio
TI In Vivo Uptake of Rare Earth Metals by Triple-Negative Breast Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Triple-negative breast cancer; Rare earth metals (REM); Europium (Eu); Dysprosium (Dy); Praseodymium (Pr); Elemental microanalysis
ID Triple-negative breast cancer; Rare earth metals (REM); Europium (Eu); Dysprosium (Dy); Praseodymium (Pr); Elemental microanalysis
AB Rare earth metals (REM) are a group of 17 chemical elements in the periodic table, namely scandium (Sc), yttrium (Y) and the lanthanides. In relation to atomic volume and geological behavior, the lanthanides are further subdivided into light, medium and heavy REM. They find many applications in the technological field; however, their impact on the human health is still conflicting and, for many aspects, unknown. During a research program carried on 113 cases of female breast cancer, immunohistochemically categorized in Her2-positive (29 cases), Her2-negative (57 cases) and triple negative (27 cases), aimed to evaluate the role of environmental particulate in carcinogenesis by elemental microanalysis, for the first time in literature we have detected a REM uptake, in detail europium (Eu), dysprosium (Dy) and praseodymium (Pr), inside the neoplastic cells belonging to a single triple negative breast cancer. Curiously, the woman affected by this form of malignancy had worked in the ceramic industry, a well-known source of REM, during her life, and she was the one and only patient of our series to be dedicated to this activity. The medical repercussions of our findings are here discussed: in fact, a REM detection in only 1 of 113 examined cases seems to exclude active roles in breast carcinogenesis and discloses new possibilities for therapeutic developments in triple negative breast cancer.
C1 [Roncati, Luca] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
[Gatti, Morena Antonietta] National Research Council, Institute of Science and Technology for CeramicsFaenza, RA, Italy.
[Barbolini, Giuseppe] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
[Piscioli, Francesco] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Pusiol, Teresa] Provincial Health Care Services, Santa Maria del Carmine Hospital, Institute of PathologyRovereto, TN, Italy.
[Maiorana, Antonio] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, MO, Italy.
RP Roncati, L (reprint author), University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, I-41124 Modena, Italy.
EM emailmedical@gmail.com
CR Connelly NG, Damhus T, Hartshorn RM, Hutton AT, 2005, Nomenclature of inorganic chemistry: IUPAC recommendations. RSC Publishing, Cambridge
Gschneidner KA, Cappellen J, 1987, 1787–1987 two hundred years of rare earths. North-Holland, Rare Earth Information Center
Haxel GB, Hedrick JB, Orris GJ, 2002, Rare earth elements - critical resources for high technology. U.S. Geological Survey. http://pubs.usgs.gov/fs/2002/fs087-02/fs087-02.pdf. Accessed 20 November 2002
Zhang J, Chen Q,Wang N, Zhang J, 2003, Levels and distribution of 15 rare earth elements in tumor and normal lung tissue from the patients with lung cancer. Wei Sheng Yan Jiu 32:423–426
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Roncati L, Barbolini G, Piacentini F, Piscioli F, Pusiol T, Maiorana A, 2016, Prognostic factors for breast cancer: an immunomorphological update. Pathol Oncol Res 22:449–452
Gatti AM, Montanari S, 2005, Risk assessment of microparticles and nanoparticles and human health. In: Nalwa HS, ed, Handbook of nanostructured biomaterials and their applications in nanobiotechnology. American Scientific Publishers, Portland, pp 347–369
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Shibata N, Pennycook SJ, Gosnell TR, Painter GS, Shelton WA, Becher PF, 2004, Observation of rare-earth segregation in silicon nitride ceramics at subnanometre dimensions. Nature 428:730–733
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Roncati L, Barbolini G, Gatti AM, Pusiol T, Piscioli F, Maiorana A, 2016, The uncontrolled sialylation is related to chemoresistant metastatic breast cancer. Pathol Oncol Res 22:869–873
FoulkesWD, Smith IE, Reis-Filho JS, 2010, Triple-negative breast cancer. N Engl J Med 363:1938–1948
Hudis CA, Gianni L, 2011, Triple-negative breast cancer: an unmet medical need. Oncologist 16:1–11
Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B et al, 2008, Comparison of triple-negative and estrogen receptor-positive/ progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer 112:995–1000
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 161
EP 165
DI 10.1007/s12253-017-0209-3
PG 5
ER
PT J
AU Cserni, G
Zombori, T
Andreu, X
Bianchi, S
Regitnig, P
Amendoeira, I
Balmativola, D
Kovacs, A
Cordoba, A
Reiner, A
Kulka, J
Kaya, H
Liepniece-Karele, I
Quinn, C
Kovari, B
AF Cserni, Gabor
Zombori, Tamas
Andreu, Xavier
Bianchi, Simonetta
Regitnig, Peter
Amendoeira, Isabel
Balmativola, Davide
Kovacs, Aniko
Cordoba, Alicia
Reiner, Angelika
Kulka, Janina
Kaya, Handan
Liepniece-Karele, Inta
Quinn, Cecily
Kovari, Bence
TI Is Regression after Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer Different in Sentinel and Non-sentinel Nodes?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sentinel lymph node; Non-sentinel lymph node; Breast cancer; Neoadjuvant therapy; Selective regression
ID Sentinel lymph node; Non-sentinel lymph node; Breast cancer; Neoadjuvant therapy; Selective regression
AB Tumor draining sentinel lymph nodes (SLNs) are the sites of selective changes as compared to non-SLNs. They show features of tumor-reactive lymphadenopathy, including increased total number of functional blood vessels, but a relative immunosuppressed status has also been described in them. We explored the hypothesis of a selective regression or non-regression in SLNs versus non-SLNs in 142 patients with 110 estrogen receptor-positive and 32 estrogen receptornegative tumors undergoing both SLN biopsy and axillary lymph node dissection after neoadjuvant therapy by assessing the tumoral (metastatic) and regression statuses of SLNs and non-SLNs separately. Of the 89 cases with signs of nodal regression, 22 cases (25%) were in favor of a selective nonregression in SLNs, 18 cases (20%) were supportive of a selective and more pronounced regression in the SLNs and the remaining showed equal degrees of regression or nonregression in SLNs and non-SLNs. The results indicate that there is no obvious difference in the degree of regressive histological changes shown by SLNs and NSLNs. Therefore, this phenomenon may not be a major contributor to the higher false negative rate of SLN biopsy after neoadjuvant treatment.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, 6000 Kecskemet, Hungary.
[Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u 1, 6725 Szeged, Hungary.
[Andreu, Xavier] University Autonoma Barcelona, Corporacio Sanitaria Parc Tauli, Department of Pathology, 08202 Sabadell, Spain.
[Bianchi, Simonetta] AOU Careggi, Department of Surgery and Translational Medicine, Largo G. A. Brambilla 3, 50134 Florence, Italy.
[Regitnig, Peter] Medical University of Graz, Department of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
[Amendoeira, Isabel] Centro Hospitalar de Sao Joao e IPATIMUP, Laboratorio de Anatomia Patologica, 4440-563 Porto, Portugal.
[Balmativola, Davide] IRCCS, Fondazione del Piemonte per l’Oncologia (FPO), Candiolo Cancer Institute, Str. Prov. 142, km 3.95, 10060 Candiolo, Italy.
[Kovacs, Aniko] Sahlgrenska University Hospital, Department of Clinical Pathology and Genetics, Gula straket 8, 41345 Gothenburg, Sweden.
[Cordoba, Alicia] Complejo Hospitalario de Navarra, Department of Pathology, Irunlarrea 3, 31008 Navarra, Spain.
[Reiner, Angelika] Donauspital, Pathologisch-Bakteriologisches Institut, Langobardenstraße, 122 Vienna, Austria.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kaya, Handan] Marmara University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Liepniece-Karele, Inta] Riga East Clinical University Hospital, Pathology Centre, Hipokrata St 2, LV-1038 Riga, Latvia.
[Quinn, Cecily] St. Vincent’s University Hospital, Elm ParkDublin, Ireland.
[Kovari, Bence] University of Szeged, Department of Pathology, Allomas u 1, 6725 Szeged, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, 6000 Kecskemet, Hungary.
EM cserni@freemail.hu
CR Greenall MJ, 1995, Why I favour axillary node sampling in the management of breast cancer. Eur J Surg Oncol 21:2–5
Cserni G, 1999, Estimating the overlap between sentinel lymph nodes and axillary node samples in breast cancer. Pathol Oncol Res 5:129–133
Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, Tsarfaty I, Hudson E, Jackson DG, Petillo D, Chen J, Resau JH, Teh BT, 2006, Preparing the "soil": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res 66:10365–10376
Schule JM, Bergkvist L, Hakansson L, Gustafsson B, Hakansson A, 2004, CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-zeta chain expression. J Transl Med 2:45., DOI 10.1186/1479-5876-2-45
Schule J, Bergkvist L, Hakansson L, Gustafsson B, Hakansson A, 2002, Down-regulation of the CD3-zeta chain in sentinel node biopsies from breast cancer patients. Breast Cancer Res Treat 74:33–40
Cochran AJ, Huang RR, Lee J, Ikatura E, Leong SP, Essner R, 2006, Tumour–induced immune modulation of sentinel lymph nodes. Nat Rev Immunol 6:659–670
Straver ME, Loo CE, Alderliesten T, Rutgers EJ, Vrancken Peeters MT, 2010, Marking the axilla with radioactive iodine seeds, MARI procedure, may reduce the need for axillary dissection after neoadjuvant chemotherapy for breast cancer. Br J Surg 97:1226–1231
Wells CA, Amendoeira I, Bellocq JP et al, 2012, S2: pathology update. Quality assurance guidelines for pathology. In: Perry N, Broeders M, de Wolf C et al, eds, European guidelines for quality assurance in breast cancer screening and diagnosis, 4th edn, supplements. European Commission, Office for Official Publications of the European Union, Luxembourg, pp 73–120
Mocellin S, Goldin E, Marchet A, Nitti D, 2016, Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: a systematic review and meta-analysis. Int J Cancer 138:472–480
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 167
EP 170
DI 10.1007/s12253-017-0229-z
PG 4
ER
PT J
AU Pavlov, I
Hadjiev, E
Alaikov, T
Spassova, S
Stoimenov, A
Naumova, E
Shivarov, V
Ivanova, M
AF Pavlov, Ivan
Hadjiev, Evgueniy
Alaikov, Tzvetan
Spassova, Sylva
Stoimenov, Angel
Naumova, Elissaveta
Shivarov, Velizar
Ivanova, Milena
TI Calreticulin Mutations in Bulgarian MPN Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MPNs; CALR; JAK2; MPL; Mutations
ID MPNs; CALR; JAK2; MPL; Mutations
AB Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study.We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutations. This is one of the few reports on the CALR mutations frequency in South-eastern populations. Our study shows that the frequency and patterns of these mutations is identical to those in the patients’ cohorts from Western countries. Besides we demonstrated the utility of four different methods for their detection.
C1 [Pavlov, Ivan] Medical University, Alexandrovska University Hospital, Laboratory of Clinical Immunology, 1 Georgi Sofiisky Blvd, 1431 Sofia, Bulgaria.
[Hadjiev, Evgueniy] Medical University, Alexandrovska University Hospital, Department of Clinical HematologySofia, Bulgaria.
[Alaikov, Tzvetan] Sofiamed University Hospital, Department of Clinical HematologySofia, Bulgaria.
[Spassova, Sylva] Sofiamed University Hospital, Department of Clinical HematologySofia, Bulgaria.
[Stoimenov, Angel] Sofiamed University Hospital, Laboratory of Transfusion MedicineSofia, Bulgaria.
[Naumova, Elissaveta] Medical University, Alexandrovska University Hospital, Laboratory of Clinical Immunology, 1 Georgi Sofiisky Blvd, 1431 Sofia, Bulgaria.
[Shivarov, Velizar] Sofiamed University Hospital, Department of Clinical HematologySofia, Bulgaria.
[Ivanova, Milena] Medical University, Alexandrovska University Hospital, Laboratory of Clinical Immunology, 1 Georgi Sofiisky Blvd, 1431 Sofia, Bulgaria.
RP Ivanova, M (reprint author), Medical University, Alexandrovska University Hospital, Laboratory of Clinical Immunology, 1431 Sofia, Bulgaria.
EM mivanova@intech.bg
CR Nangalia J, Grinfeld J, Green AR, 2016, Pathogenesis of myeloproliferative disorders. Annu Rev Pathol 11:101–126., DOI 10.1146/annurev-pathol-012615-044454
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, BianchiM, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR, 2013, Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369(25):2391–2405., DOI 10.1056/NEJMoa1312542
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R, 2013, Somaticmutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369(25):2379–2390., DOI 10.1056/NEJMoa1311347
IvanovaMI, Shivarov VS, Hadjiev EA, Naumova EJ, 2011, Novel multiplex bead-based assay with LNA-modified probes for detection of MPL exon 10 mutations. Leuk Res 35(8):1120–1123., DOI 10.1016/j.leukres.2011.04.012
Shivarov V, Ivanova M, Hadjiev E, Naumova E, 2011, Rapid quantification of JAK2 V617F allele burden using a bead-based liquid assay with locked nucleic acid-modified oligonucleotide probes. Leuk Lymphoma 52(10):2023–2026., DOI 10.3109/10428194.2011.584995
Jones AV, Ward D, Lyon M, Leung W, Callaway A, Chase A, Dent CL, White HE, Drexler HG, Nangalia J, Mattocks C, Cross NC, 2015, Evaluation of methods to detect CALR mutations in myeloproliferative neoplasms. Leuk Res 39(1): 82–87., DOI 10.1016/j.leukres.2014.11.019
Ivanova M, Shivarov V, Pavlov I, Lilakos K, Naumova E, 2016, Clinical evaluation of a novel nine-gene panel for ion torrent PGM sequencing ofmyeloidmalignancies.Mol Diagn Ther 20(1):27–32., DOI 10.1007/s40291-015-0172-1
Guenova M, Stoeva V, Dimitrova S, Gercheva L, Petrov Y, Todorieva D, Grklanov V, Tsvetkova G, Tumbeva D, Grudeva- Popova J, Petkova N, Raynov J, Sivcheva L, Dimitrova G, Zhukova M, Topalov Y, Dikov T, Balatzenko G, Mihaylov G, 2016, Baseline characteristics and risk factors for leukemia-free and overall survival in bulgarian patients with primary myelofibrosis ? A national cohort study
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 171
EP 174
DI 10.1007/s12253-017-0226-2
PG 4
ER
PT J
AU Choi, JE
Kim, SM
Song, YS
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Kim, Sung Min
Song, Yong Sang
Yoo, Jin Nam
Lee, Hyung Sug
TI Low Frequent Mutation of ARHGAP35, a Candidate Tumor Suppressor Gene, in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE ARHGAP35; RHO inhibition; Mutation; Cancers; Microsatellite instability
ID ARHGAP35; RHO inhibition; Mutation; Cancers; Microsatellite instability
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 175
EP 176
DI 10.1007/s12253-017-0208-4
PG 2
ER
PT J
AU Robert, L
AF Robert, Ladislas
TI Tribute to Prof. George Klein
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Robert, Ladislas] University of Paris 5, Hotel Dieu HospitalParis, France.
RP Robert, L (reprint author), University of Paris 5, Hotel Dieu Hospital, Paris, France.
EM Lrobert5@orange.fr
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 177
EP 177
DI 10.1007/s12253-017-0207-5
PG 1
ER
PT J
AU Soike, MTh
Maize, CJ
Ralston, SJ
Hayes, B
Swick, J
AF Soike, M Thomas
Maize, C John
Ralston, S Jonathan
Hayes, Benjamin
Swick, Julie
TI Dual Immunohistochemical Detection of Mitoses in Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Soike, M Thomas] Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 171 Ashley Avenue, MSC 908, 29425 Charleston, SC, USA.
[Maize, C John] Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 171 Ashley Avenue, MSC 908, 29425 Charleston, SC, USA.
[Ralston, S Jonathan] Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 171 Ashley Avenue, MSC 908, 29425 Charleston, SC, USA.
[Hayes, Benjamin] Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 171 Ashley Avenue, MSC 908, 29425 Charleston, SC, USA.
[Swick, Julie] Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 171 Ashley Avenue, MSC 908, 29425 Charleston, SC, USA.
RP Soike, MTh (reprint author), Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 29425 Charleston, USA.
EM soiketm2@msha.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 179
EP 183
DI 10.1007/s12253-017-0203-9
PG 5
ER
PT J
AU Choi, JE
Kim, SM
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI TRIO Gene Encoding Trio Rho Guanine Nucleotide Exchange Factor Harbors Frameshift Mutations of in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE TRIO; Frameshift mutation; Cancer; Microsatellite instability
ID TRIO; Frameshift mutation; Cancer; Microsatellite instability
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Schmidt S, Debant A, 2014, Function and regulation of the Rho guanine nucleotide exchange factor Trio. Small GTPases 5:e29769
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Jo YS, Choi MR, Song SY, Kim MS, Yoo NJ, Lee SH, 2016, Frameshift mutations of HSPA4 and MED13 in gastric and colorectal cancers. Pathol Oncol Res 22:769–772
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 185
EP 187
DI 10.1007/s12253-017-0211-9
PG 3
ER
PT J
AU Terada, T
AF Terada, Tadashi
TI A Retrospective Case Control Study of Ductal Plate Malformation-like Features in Consecutive 200 Autopsies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Terada, Tadashi] Shizuoka City Shimizu Hospital, Department of Pathology, No. 4-27-1, Kita-Ando, Aoi-ku, 420-8527 Shizuoka, Japan.
RP Terada, T (reprint author), Shizuoka City Shimizu Hospital, Department of Pathology, 420-8527 Shizuoka, Japan.
EM piyo0111jp@yahoo.co.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 189
EP 194
DI 10.1007/s12253-017-0201-y
PG 6
ER
PT J
AU Warth, A
AF Warth, Arne
TI cR and pR: The Residual Tumor Classification Revisited
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Warth, Arne] University of Heidelberg, Department of Pathology, INF 224, D-69120 Heidelberg, Germany.
RP Warth, A (reprint author), University of Heidelberg, Department of Pathology, D-69120 Heidelberg, Germany.
EM arne.warth@med.uni-heidelberg.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2018
VL 24
IS 1
BP 195
EP 196
DI 10.1007/s12253-017-0221-7
PG 2
ER
PT J
AU Zidi, S
AF Zidi, Sabrina
TI RETRACTED ARTICLE: Impact of Toll-Like Receptors 2/3/4/9, IL-1-α/β and TNF-α Polymorphisms in Cervical Cancer Susceptibility in Tunisia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
AB This article published in Pathology and Oncology Research, has been retracted at the request of Editor-in-Chief and the authors Hasibe Verdi, Yaprak Yilmaz-Yalcin, A. C. Yazici and Fatma- Belgin Atac. The reasons for the retraction of the article are: – There are substantial parts in the article that were previously published in the article: "Involvement of Toll-like receptors in cervical cancer susceptibility among Tunisian women" by Sabrina Zidi, Hasibe Verdi, Yaprak Yilmaz- Yalcin, A.C. Yazici, Ezzedine Gazouani, Amel Mezlini, Fatma-Belgin Atac, Besma Yacoubi-Loueslati, Bulletin du Cancer, 2014; 101: E31-E35, DOI: 10.1684/bdc.2014. 2037. Although the article published in Pathology and Oncology Research uses a larger control group the two papers have very similar content, addressing the same problem with the same methodology and the differences in the articles were considered too minor. – In addition, this article was submitted to Pathology and Oncology Research without the knowledge or consent of all the authors.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 197
EP 197
DI 10.1007/s12253-014-9793-7
PG 1
ER
PT J
AU Schneider, T
Rosta, A
Losonczy, H
Radvanyi, G
Ujj, Gy
Egyed, M
Illes,
Jakucs, J
Szerafin, L
Gasztonyi, Z
Masszi, T
Ivanyi, J
Demeter, J
Dombi, P
Toth, A
Borbenyi, Z
AF Schneider, Tamas
Rosta, Andras
Losonczy, Hajna
Radvanyi, Gaspar
Ujj, Gyorgy
Egyed, Miklos
Illes, Arpad
Jakucs, Janos
Szerafin, Laszlo
Gasztonyi, Zoltan
Masszi, Tamas
Ivanyi, Janos
Demeter, Judit
Dombi, Peter
Toth, Antal
Borbenyi, Zita
TI Efficacy and Tolerability of a 2-Year Rituximab Maintenance Therapy in Patients with Advanced Follicular Lymphoma after Induction of Response with Rituximab-Containing First Line-Regimens (HUSOM Study)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Follicular lymphoma; Rituximab; Maintenance; Event-free survival; Drug safety
ID Follicular lymphoma; Rituximab; Maintenance; Event-free survival; Drug safety
AB Follicular lymphoma is a lymphoid malignancy commonly showing slow progression which makes the treatment of the disease challenging. Rituximab monotherapy and rituximab added to standard chemotherapy has been proven to increase survival among patients with advanced stage of the disease. However, the benefit of a rituximab maintenance therapy after induction was still unclear at the time of the initiation of this study. HUSOM was a phase III open-label, single-arm, multi-centre study aimed to assess the efficacy and the safety of the 12 cycles of rituximab (375 mg/m2 every 8 weeks) maintenance therapy in patients had already presented partial or complete response to R-CVP or R-CHOP. Efficacy endpoints such as event-free survival and overall survival were estimated. Adverse events were recorded during the entire course of the study. A total number of 124 patients were enrolled by 15 Hungarian study sites. Out of these, 86 patients received 12 cycles of rituximab and 69 patients completed the 3-year follow-up phase as well. The probabilities of the event free survival and progression at 4.3 years were estimated to be 70.3% and 74.4%, respectively. The overall and the disease free survival at 4 years were estimated to be 90.7%and 87.9%, respectively. A total number of 85 adverse events were reported during the study out of which 5 AEs were considered to be related to the administration of rituximab. Analyses of the efficacy variables have revealed comparable results to those reported by controlled clinical trials (EORTC 20981, PRIMA) conducted in parallel with the HUSOM study.
C1 [Schneider, Tamas] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Rosta, Andras] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
[Losonczy, Hajna] University of Pecs, I. Department of Internal Medicine, Ifjusag ut 13, 7624 Pecs, Hungary.
[Radvanyi, Gaspar] Borsod-Abauj-Zemplen County Hospital, 2nd Department of Internal Medicine, Csabai kapu 9-11, 3529 Miskolc, Hungary.
[Ujj, Gyorgy] Jasz-Nagykun-Szolnok County Hetenyi Geza Hospital, I. Department of Internal Medicine, Toszegi ut 21, 5000 Szolnok, Hungary.
[Egyed, Miklos] Kaposi Mor Hospital, Department of Internal Medicine and Hematology, Tallian Gyula u. 20-34, 7400 Kaposvar, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Jakucs, Janos] Bekes County Pandy Kalman Hospital, Department of Internal Medicine, Semmelweis u. 1, 5700 Gyula, Hungary.
[Szerafin, Laszlo] Szabolcs-Szatmar-Bereg County Josa Andras Hospital, Department of Haematology, Szent Istvan u. 68, 4400 Nyiregyhaza, Hungary.
[Gasztonyi, Zoltan] Petz Aladar County Hospital, II. Department of Internal Medicine and Hematology, Vasvari Pal u. 2-4, 9024 Gyor, Hungary.
[Masszi, Tamas] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Nagyvarad ter 1, 1097 Budapest, Hungary.
[Ivanyi, Janos] Vas County Markusovszky Hospital, Department of Hematology, Markusovszky L. u. 5, 9700 Szombathely, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor u. 2/A, 1083 Budapest, Hungary.
[Dombi, Peter] Szent Borbala Hospital, Department of Hematology, Dozsa Gyorgy ut 77, 2800 Tatabanya, Hungary.
[Toth, Antal] Tolna County Balassa Janos Hospital, IV. Department of Internal Medicine, Beri Balogh Adam u. 5-7, 7100 Szekszard, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Koranyi Fasor 6, 6720 Szeged, Hungary.
RP Schneider, T (reprint author), National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, 1122 Budapest, Hungary.
EM schneidertamas@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 199
EP 205
DI 10.1007/s12253-017-0234-2
PG 7
ER
PT J
AU Malik, ASh
Khan, SM
Dar, M
Mahboob, UH
Shah, AM
Shafi, MSh
Mudassar, S
AF Malik, A Showkat
Khan, S Mosin
Dar, Majeed
Mahboob, Ul Hussain
Shah, A Mohammad
Shafi, M Sheikh
Mudassar, Syed
TI Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Survival; Hazard ratio; Non-small cell lung cancer; LATS1; LATS2
ID Lung cancer; Survival; Hazard ratio; Non-small cell lung cancer; LATS1; LATS2
AB Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples.We found promoter hypermethylation frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with hypermethylation were significantly lower. Multivariable analysis confirmed that LATS1 under expression increased the hazard of death after adjusting for other clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was associated with overall short survival. LATS1 is an independent prognostic factor and may play an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.
C1 [Malik, A Showkat] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, Soura, 190011 Srinagar, Kashmir, India.
[Khan, S Mosin] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, Soura, 190011 Srinagar, Kashmir, India.
[Dar, Majeed] Sher-I-Kashmir Institute of Medical Sciences, Department of Cardiovascular and Thoracic Surgery, Soura, 190011 Srinagar, Kashmir, India.
[Mahboob, Ul Hussain] University of Kashmir, Department of Biotechnology, 190006 Srinagar, Kashmir, India.
[Shah, A Mohammad] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, Soura, 190011 Srinagar, Kashmir, India.
[Shafi, M Sheikh] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, Soura, 190011 Srinagar, Kashmir, India.
[Mudassar, Syed] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, Soura, 190011 Srinagar, Kashmir, India.
RP Mudassar, S (reprint author), Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Srinagar, India.
EM syed.mudassar@skims.ac.in
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Xia H, Qi H, LiY, Pei J, Barton J, Blackstad M, Xu T, TaoW(2002, LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene 21:1233–1241
Yang X, Li DM, Chen W, Xu T, 2001, Human homologue of Drosophila LATS, negatively regulate growth by inducing G(2)M arrest or apoptosis. Oncogene 20:6516–6523
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Luo SY, Sit KY, Sihoe AD, Suen WS et al, 2014, Abberant large tumor suppressor 2, LATS2, gene expression correlates with EGFR mutation and survival in lung adenocarcinomas. Lung Cancer 85: 282–292
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 207
EP 214
DI 10.1007/s12253-017-0225-3
PG 8
ER
PT J
AU Li, Sh
Li, R
Wang, H
Li, L
Li, H
Li, Y
AF Li, Shuang
Li, Rui
Wang, Heping
Li, Lisha
Li, Huiyu
Li, Yulin
TI The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Transcriptome; Chronic pancreatitis; Pancreatic cancer; Network analysis; Key factors
ID Transcriptome; Chronic pancreatitis; Pancreatic cancer; Network analysis; Key factors
AB An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction.We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.
C1 [Li, Shuang] Ministry of Education, Jilin University, College of Basic Medical Sciences, The Key Laboratory of PathobiologyChangchun, China.
[Li, Rui] Coordination Center of China, National Computer Network Emergency Response Technical TeamBeijing, China.
[Wang, Heping] Tongji Medical School, Tongji Hospital, Department of NeurosurgeryWuhan, China.
[Li, Lisha] Ministry of Education, Jilin University, College of Basic Medical Sciences, The Key Laboratory of PathobiologyChangchun, China.
[Li, Huiyu] Ministry of Education, Jilin University, College of Basic Medical Sciences, The Key Laboratory of PathobiologyChangchun, China.
[Li, Yulin] Ministry of Education, Jilin University, College of Basic Medical Sciences, The Key Laboratory of PathobiologyChangchun, China.
RP Li, L (reprint author), Ministry of Education, Jilin University, College of Basic Medical Sciences, The Key Laboratory of Pathobiology, Changchun, China.
EM lilisha@jlu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 215
EP 222
DI 10.1007/s12253-017-0217-3
PG 8
ER
PT J
AU Liu, Y
Wang, W
Li, Y
Sun, F
Lin, J
Li, L
AF Liu, Yansong
Wang, Wei
Li, Yan
Sun, Feifei
Lin, Jiaxiang
Li, Li
TI CKS1BP7, a Pseudogene of CKS1B, is Co-Amplified with IGF1R in Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; CKS1BP7; IGF1R; Quantitative multi-gene fluorescence in situ hybridization
ID Breast cancer; CKS1BP7; IGF1R; Quantitative multi-gene fluorescence in situ hybridization
AB Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multigene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8% of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2%of all patients. The two events often co-existed (p = 0.01). Within the same tumors, identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma. Moreover, amplification of both genes was more frequent in aneuploidy tumors and the tumors with high ki67, but wasn’t associated with patients’ outcome. In summary, CKS1BP7 amplification is a frequent event in breast cancer and often co-occurs with amplified IGF1R, which provides evidence supporting the interactions between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early detection and predict prognosis in breast cancer.
C1 [Liu, Yansong] Shandong Cancer Hospital Affiliated to Shandong University, Department of Breast Surgery, 250117 Jinan, Shandong, China.
[Wang, Wei] Shandong Provincial Western Hospital, Department of Obstetrics and Gynecology, 250022 Jinan, Shandong, China.
[Li, Yan] Shandong Cancer Hospital and Institute Affiliated to Shandong University, Department of Medical Oncology, 250117 Jinan, Shandong, China.
[Sun, Feifei] The Second Hospital of Shandong University, Department of Pathology, 44#Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Lin, Jiaxiang] The Second Hospital of Shandong University, Department of Pathology, 44#Wenhuaxi Road, 250012 Jinan, Shandong, China.
[Li, Li] The Second Hospital of Shandong University, Department of Pathology, 44#Wenhuaxi Road, 250012 Jinan, Shandong, China.
RP Li, L (reprint author), The Second Hospital of Shandong University, Department of Pathology, 250012 Jinan, China.
EM lillie6636@sdu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 223
EP 229
DI 10.1007/s12253-017-0224-4
PG 7
ER
PT J
AU Zelga, P
Przybylowska-Sygut, K
Zelga, M
Dziki, A
Majsterek, I
AF Zelga, Piotr
Przybylowska-Sygut, Karolina
Zelga, Marta
Dziki, Adam
Majsterek, Ireneusz
TI The 116G > A MSH6 and IVS1-1121C > T PMS2 Genes Polymorphisms Modulate the Risk of the Sporadic Colorectal Cancer Development in Polish Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; SNP; MSH6; PMS2; DNA MMR
ID Colorectal cancer; SNP; MSH6; PMS2; DNA MMR
AB Colorectal cancer (CRC) is one of the most common cancers worldwide. DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication. MMR defects were found to be associated with hereditary non-polyposis colorectal cancer (HNPCC) and a subset of sporadic colon cancers. The inheritance of common variations in MMR genes may influences individual susceptibility to the development of colorectal cancer. The purpose of the study was to evaluate the association between gene polymorphisms Glu39Gly (c.116G > A) of MSH6 gene and IVS1-1121C > T of PMS2 gene and sporadic colorectal cancer risk, in a case-control study comprising 200 patients and 200 controls origination from polish population. DNA was isolated from peripheral blood lymphocytes of enrolled patients, and gene polymorphisms were analysed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for MSH6 and TaqMan for PMS2. G/A variant of Glu39Gly (c.116G > A) genotype was associated with an increased risk of colorectal cancer (OR 1,65 95% CI:1,01–2,69 p = 0.44). Presence of A allele was also significantly higher in patient with CRC (OR 1,57 95% CI: 1,04–2,38 p = 0.032). Prevalence of this genotype was also markedly higher in females and patients above 60 years in CRC group (OR 2.25 95% CI: 1.22–4.14 p = 0.0098 and OR 2.74 95% CI: 1.27–5.93 p = 0.0097 respectively). None of such correlations was observed for genotype variants of IVS1-1121C > T PMS2. In conclusion, our data suggests that MSH6 Glu39Gly polymorphism is associated with the risk of developing sporadic colorectal cancer in polish population. Linkage to the female gender, onset above 60 years old and further increase of risk when combined with wild-type allele of PMS2 IVS1-1121C > T polymorphism indicates defective mismatch repair system.
C1 [Zelga, Piotr] Medical University of Lodz, Department of General and Colorectal Surgery, Plac Hallera 1, 90-647 Lodz, Poland.
[Przybylowska-Sygut, Karolina] Medical University of Lodz, Department of Chemistry and Clinical BiochemistryLodz, Poland.
[Zelga, Marta] Medical University of Lodz, Department of General and Colorectal Surgery, Plac Hallera 1, 90-647 Lodz, Poland.
[Dziki, Adam] Medical University of Lodz, Department of General and Colorectal Surgery, Plac Hallera 1, 90-647 Lodz, Poland.
[Majsterek, Ireneusz] Medical University of Lodz, Department of Chemistry and Clinical BiochemistryLodz, Poland.
RP Zelga, P (reprint author), Medical University of Lodz, Department of General and Colorectal Surgery, 90-647 Lodz, Poland.
EM piotr_zelga@op.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 231
EP 235
DI 10.1007/s12253-017-0231-5
PG 5
ER
PT J
AU Rubovszky, G
Budai, B
Ganofszky, E
Horvath, Zs
Juhos,
Madaras, B
Nagy, T
Szabo, E
Pinter, T
Toth, E
Nagy, P
Lang, I
Hitre, E
AF Rubovszky, Gabor
Budai, Barna
Ganofszky, Erna
Horvath, Zsolt
Juhos, Eva
Madaras, Balazs
Nagy, Tunde
Szabo, Eszter
Pinter, Tamas
Toth, Erika
Nagy, Peter
Lang, Istvan
Hitre, Erika
TI Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acneiform rash; Predictive marker; Cetuximab; Chemotherapy; Cholangiocarcinoma
ID Acneiform rash; Predictive marker; Cetuximab; Chemotherapy; Cholangiocarcinoma
AB Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m2/week, loading dose: 400 mg/m2), gemcitabine (1000 mg/m2 on day 1 and 8), and capecitabine (1300 mg/m2/day on days 1–14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24–40) and 54 (43–67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.
C1 [Rubovszky, Gabor] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Budai, Barna] National Institute of Oncology, Department of BiochemistryBudapest, Hungary.
[Ganofszky, Erna] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Horvath, Zsolt] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Juhos, Eva] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Madaras, Balazs] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Nagy, Tunde] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Szabo, Eszter] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Pinter, Tamas] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Nagy, Peter] National Institute of Oncology, Department of BiochemistryBudapest, Hungary.
[Lang, Istvan] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Hitre, Erika] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
RP Rubovszky, G (reprint author), National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, 1122 Budapest, Hungary.
EM garub@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 237
EP 244
DI 10.1007/s12253-017-0238-y
PG 8
ER
PT J
AU Abbaszadegan, RM
Moghbeli, M
AF Abbaszadegan, Reza Mohammad
Moghbeli, Meysam
TI Role of MAML1 and MEIS1 in Esophageal Squamous Cell Carcinoma Depth of Invasion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NOTCH signaling pathway; HOX; mRNA expression; Transcription factor; Self renewal
ID NOTCH signaling pathway; HOX; mRNA expression; Transcription factor; Self renewal
AB Homeobox (HOX) transcription factors and NOTCH signaling pathway are critical regulators of stem cell functions, cell fate in development and homeostasis of gastrointestinal tissues. In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation between MAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. Fifty one ESCC cases were enrolled to assess the levels of Meis1 and Maml1 mRNA expression using real-time polymerase chain reaction (PCR). Only 3 out of 51 (5.9%) cases had MEIS1/MAML1 under expression and 2/51 (3.9%) cases had MEIS1/MAML1over expression. Nine out of 51 samples (17.6%) have shown MEIS1 under expression and MAML1 over expression. There was a significant correlation between MAML1and MEIS1mRNA expressions (p ≤ 0.05). There were significant correlations between MEIS1 under/MAML1 over expressed cases and tumor location (p = 0.05), tumor depth of invasion (p = 0.011), and sex (p = 0.04). Our results showed that MEIS1 may have a negative role in regulation of MAML1expression during the ESCC progression.
C1 [Abbaszadegan, Reza Mohammad] Mashhad University of Medical Sciences, Immunology Research Center, Avicenna Research Institute, Division of Human GeneticsMashhad, Iran.
[Moghbeli, Meysam] North Khorasan University of Medical SciencesBojnurd, Iran.
RP Moghbeli, M (reprint author), North Khorasan University of Medical Sciences, Bojnurd, Iran.
EM m.moghbeli@nkums.ac.ir;Meysam_moghbeli@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 245
EP 250
DI 10.1007/s12253-017-0243-1
PG 6
ER
PT J
AU Jianwei, Z
Qi, L
Quanquan, X
Tianen, W
Qingwei, W
AF Jianwei, Zhang
Qi, Li
Quanquan, Xu
Tianen, Wang
Qingwei, Wang
TI TMPRSS4 Upregulates TWIST1 Expression through STAT3 Activation to Induce Prostate Cancer Cell Migration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Transmembrane protease serine 4; Epithelial-mesenchymal transition; Migration; Signal transducer and activator of transcription 3; TWIST1
ID Prostate cancer; Transmembrane protease serine 4; Epithelial-mesenchymal transition; Migration; Signal transducer and activator of transcription 3; TWIST1
AB Transmembrane protease serine 4 (TMPRSS4), a type-II transmembrane serine protease, is involved in the development and progression of wide range of tumors. However, the biological role of TMPRSS4 in prostate cancer remains obscure. Here, we investigated the effect of TMPRSS4 on proliferation and migration in prostate cancer and potential mechanisms. Our findings demonstrated over-expression of TMPRSS4 promoted the PC3 prostate cancer cells migration, which could be reversed by TMPRSS4 silencing. TMPRSS4 induced TWIST1 expression and followed progression of EMT along with upregulation of N-cadherin and downregulation of E-cadherin via STAT3 phosphorylation. Silencing TWIST1 significantly attenuated TMPRSS4-induced PC3 migration. Moreover, knockdown of STAT3 effectively attenuated TMPRSS4- induced TWIST1 expression and TWIST1 promoter activity. Taken together, we demonstrated a mechanistic cascade of TMPRSS4 up-regulating STAT3 activation and subsequent TWIST1 expression, leading to prostate cancer migration.
C1 [Jianwei, Zhang] The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, Henan Province, China.
[Qi, Li] The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, Henan Province, China.
[Quanquan, Xu] The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, Henan Province, China.
[Tianen, Wang] The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, Henan Province, China.
[Qingwei, Wang] The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, Henan Province, China.
RP Qingwei, W (reprint author), The First Affiliated Hospital of Zhengzhou University, Department of Urology, 450052 Zhengzhou, China.
EM kyl361@126.com
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30
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Min HJ, Lee MK, Lee JW et al, 2014,, 2014, TMPRSS4 induces cancer cell invasion through pro-uPAprocessing. BiochemBiophys Res Commun 446(1):1–7
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 251
EP 257
DI 10.1007/s12253-017-0237-z
PG 7
ER
PT J
AU Zombori, T
Cserni, G
AF Zombori, Tamas
Cserni, Gabor
TI Immunohistochemical Analysis of the Expression of Breast Markers in Basal-like Breast Carcinomas Defined as Triple Negative Cancers Expressing Keratin 5
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal-like; Triple negative breast cancer; GATA-3; Mammaglobin; GCDFP-15; NY-BR-1
ID Basal-like; Triple negative breast cancer; GATA-3; Mammaglobin; GCDFP-15; NY-BR-1
AB Estrogen and progesterone receptors are possible markers for suggesting a mammary origin of metastatic carcinoma, but are useless in cases of triple negative breast cancers (TNBC). Five other potential markers of breast origin were investigated on tissue microarrays in a series of TNBCs showing keratin 5 expression, consistent with a basal-like phenotype. GATA-3 staining was observed in 82 of 115 triple negative cases (71.3%) including 23 cases with >5% staining. Mammaglobin staining was detected in 30 cases (26.0%) including 12 with >5% staining. GCDFP-15 was seen in 23 cases (20.0%) including 9 with >5% staining. NY-BR-1 positivity was present in 7 cases (6.0%) including 3 patients with >5% staining. BCA-225 staining was observed in 74 cases (64.3%); however this latter marker lacks also specificity owing to the reported widespread staining in other malignancies. GATA-3, mammaglobin and GCDFP-15 coexpression was seen in one case (0.9%), whereas GATA-3 and mammaglobin or mammaglobin and GCDFP-15 coexpression was present in 2 and 2 cases (1.7%), respectively. Using at least 5% staining as cut-off, the expression of any of the last 4 markers was 34.7%. The expression of GATA-3, mammaglobin, GCDFP- 15 and NY-BR-1 is lower in TNBC-s than in breast carcinomas in general, and this may be even lower in basal-like carcinomas. Although these markers are not fully specific, by using them, a subset of basal-like TNBC-s can be identified as of mammary origin. However, a substantial proportion will not show any staining with any of these markers.
C1 [Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
RP Zombori, T (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM zomtam@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 259
EP 267
DI 10.1007/s12253-017-0246-y
PG 9
ER
PT J
AU Cui, G
Li, C
Xu, G
Sun, Z
Zhu, L
Li, Z
Zheng, W
Li, J
Yuan, A
AF Cui, Guanglin
Li, Can
Xu, Gang
Sun, Zhenglu
Zhu, Li
Li, Zhengfen
Zheng, Wei
Li, Junling
Yuan, Aping
TI Tumor-Associated Fibroblasts and Microvessels Contribute to the Expression of Immunosuppressive Factor Indoleamine 2, 3-Dioxygenase in Human Esophageal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Fibroblasts; Endothelial cells; Indoleamine 2; 3-dioxygenase; Immunosuppression; carcinoma; esophagus
ID Fibroblasts; Endothelial cells; Indoleamine 2; 3-dioxygenase; Immunosuppression; carcinoma; esophagus
AB Recent studies have provided considerable evidence to support the hypothesis that tumor stroma plays a crucial role in the induction of immune tolerance to human cancers. Here, we investigated the contribution of reactive stromal tumorassociated fibroblasts (TAFs) and microvessels to the immunosuppressive factor indoleamine 2,3-dioxygenase (IDO) expression in the ESCC microenvironment. The immunohistochemical (IHC) analyses demonstrated a significant increased densities of TAFs and microvessels in the ESCC stroma, double IHCs showed that these increased TAFs and microvessels were with a high proliferation activity. Further IHC examinations revealed that increased expression of IDO were frequently observed in the stromal cells with TAF morphology and microvessels. Double immunofluorescence examinations confirmed the colocalization of IDO positive cells with SMA-alpha positive TAFs and CD34 positive endothelial cells in the ESCC stroma. Our current findings strongly suggest that the activated stromal TAFs and endothelial cells of microvessels contribute to the expression of IDO and then the orchestration of immunosuppressive microenvironment.
C1 [Cui, Guanglin] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Li, Can] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Xu, Gang] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Sun, Zhenglu] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Zhu, Li] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Li, Zhengfen] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Zheng, Wei] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Li, Junling] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
[Yuan, Aping] the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal DiseasesZhengzhou, Henan, China.
RP Cui, G (reprint author), the Second Affiliated Hospital of Zhengzhou University, Research Group of Gastrointestinal Diseases, Zhengzhou, China.
EM guanglin.cui@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 269
EP 275
DI 10.1007/s12253-017-0244-0
PG 7
ER
PT J
AU El-Balat, A
Schmeil, I
Karn, Th
Becker, S
Sanger, N
Holtrich, U
Arsenic, R
AF El-Balat, Ahmed
Schmeil, Iryna
Karn, Thomas
Becker, Sven
Sanger, Nicole
Holtrich, Uwe
Arsenic, Ruza
TI TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; Borderline tumors; Histological subtypes; Prognosis
ID Ovarian cancer; Borderline tumors; Histological subtypes; Prognosis
AB Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P < 0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.
C1 [El-Balat, Ahmed] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Schmeil, Iryna] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Karn, Thomas] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Becker, Sven] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Sanger, Nicole] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Holtrich, Uwe] Goethe University Frankfurt, Department of Obstetrics and Gynecology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
[Arsenic, Ruza] Charite University Hospital, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
RP El-Balat, A (reprint author), Goethe University Frankfurt, Department of Obstetrics and Gynecology, 60590 Frankfurt, Germany.
EM ahmed.el-balat@kgu.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 277
EP 282
DI 10.1007/s12253-017-0240-4
PG 6
ER
PT J
AU Awkar, N
Amireh, S
Rai, S
Shaaban, H
Guron, G
Maroules, M
AF Awkar, Nelly
Amireh, Sawsan
Rai, Srijana
Shaaban, Hamid
Guron, Gunwant
Maroules, Michael
TI Association between Level of Tumor Markers and Development of VTE in Patients with Pancreatic, Colorectal and Ovarian Ca: Retrospective Case- Control Study in Two Community Hospitals
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumor markers; Venous; Thromboembolism; Colorectal; Pancreatic; Ovarian
ID Tumor markers; Venous; Thromboembolism; Colorectal; Pancreatic; Ovarian
AB The risk of venous thromboembolism (VTE) is increased in patients with cancer. However, the role of tumor markers as potential indicators of increased risk of VTE is still undetermined. In this retrospective observational case control study, levels of the tumor markers CEA, CA 19–9 and CA 125 in patients with colorectal, pancreatic, and ovarian cancer respectively, who were admitted to two community hospitals between January 2001 and December 2011, were compared between patients who were VTE positive and those who were VTE negative. The primary goal of this study was to determine whether VTE positive cancer patients had higher tumor marker levels compared to VTE negative cancer patients. In our study, 66.7% (48/72) of patients who were positive for VTE had elevated tumor markers while 65.3% (66/101) of patients who were negative for VTE had low (normal) tumor markers, indicating an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of <0.0001 (95% CI of 1.99–7.14). When the VTE group was further divided into DVT and PE groups, 70.2% (40/57) of patients in the DVT positive group had high tumor markers with a p value of <0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89) while 57.9% (11/19) of patients in pulmonary embolism positive group had high tumor markers; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). In this retrospective study of 173 individuals with a diagnosis of either colorectal, pancreatic, or ovarian Cancer, higher tumor marker levels (CEA, CA 19–9, and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant only for DVT but not for PE.
C1 [Awkar, Nelly] St Joseph’s Regional Medical Center, Department of Medical OncologyPaterson, NJ, USA.
[Amireh, Sawsan] St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 111 Central AvenueNewark, NJ, USA.
[Rai, Srijana] St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 111 Central AvenueNewark, NJ, USA.
[Shaaban, Hamid] St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 111 Central AvenueNewark, NJ, USA.
[Guron, Gunwant] St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, 111 Central AvenueNewark, NJ, USA.
[Maroules, Michael] St Joseph’s Regional Medical Center, Department of Medical OncologyPaterson, NJ, USA.
RP Shaaban, H (reprint author), St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, St Michael’s Medical Center, Newark, USA.
EM hamidshaaban@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 283
EP 287
DI 10.1007/s12253-017-0239-x
PG 5
ER
PT J
AU Aumayr, K
Fathi, O
Traub-Weidinger, T
Niederle, B
Koperek, O
AF Aumayr, Klaus
Fathi, Osmen
Traub-Weidinger, Tatjana
Niederle, Bruno
Koperek, Oskar
TI Expression of Hypoxia-Associated Protein HIF-1α in Follicular Thyroid Cancer is Associated with Distant Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIF-1α; Hypoxia-associated proteins; Tenascin; Follicular thyroid cancer; Desmoplastic stroma reaction; Metastasis
ID HIF-1α; Hypoxia-associated proteins; Tenascin; Follicular thyroid cancer; Desmoplastic stroma reaction; Metastasis
AB Follicular thyroid carcinomas (FTCs) are the second most common malignant neoplasia of the thyroid and in general its prognosis is quite favorable. However, the occurrence of metastases or non-responsiveness to radioiodine therapy worsens the prognosis considerably. We evaluated immunohistochemically the expression of hypoxiaassociated proteins by hypoxia-induced factor 1α (HIF-1α), the stroma-remodeling marker Tenascin C, as well as markers for the epithelial-mesenchymal transition (EMT), namely Ecadherin and slug in a series of 59 sporadic FTCs. In addition, various clinicopathologic parameters were assessed like TNM-staging, age, tumor size as well as tumor characteristics like desmoplasia, necrosis, and calcification. Overexpression of HIF-1α was seen in 29 of 59 tumors (49.2%) including 21 (35.6%) FTC with strong expression of tumor cell groups. HIF-1α correlated significantly with metastasis (p < 0.001; Mann-Whitney U test), degree of desmoplasia (p = 0.042, Kruskal-Wallis test), tenascin C expression (p = 0.042, Kruskal-Wallis test), calcification (p < 0.025, Kruskal–Wallis test), necrosis (p = 0.002), age (p = 0.011, Kruskal-Wallis test) and tumor stage UICC (p = 0.022, Kruskal-Wallis test). Furthermore, metastasis was associated with the degree of desmoplasia (p = 0.014; Fisher’s exact test), calcification (p = 0.008, Fisher’s exact test), necrosis (p = 0.042, Fisher’s exact test), tumor size (p = 0.015, Mann-Whitney U test), and age (p = 0.001, Mann-Whitney U test). In a Cox proportional hazards model, only metastasis remained as an independent risk factor for overall survival (hazard rate: 10.2 [95% CI, 02.19 to 47.26]; p = 0.003). Our data suggest that HIF-1α plays a critical role in the remodeling of the extracellular matrix as well as metastasizing process of follicular thyroid carcinoma and targeting hypoxia-associated and -regulated proteins may be considered as potential targets for personalized medicine.
C1 [Aumayr, Klaus] Medical University of Vienna, Department of Pathology, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Fathi, Osmen] Medical University of Vienna, Department of Pathology, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Traub-Weidinger, Tatjana] Medical University of Vienna, Department of RadiologyVienna, Austria.
[Niederle, Bruno] Medical University of Vienna, Department of SurgeryVienna, Austria.
[Koperek, Oskar] Medical University of Vienna, Department of Pathology, Waehringer Guertel 18-20, 1090 Vienna, Austria.
RP Koperek, O (reprint author), Medical University of Vienna, Department of Pathology, 1090 Vienna, Austria.
EM oskar.koperek@meduniwien.ac.at
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 289
EP 296
DI 10.1007/s12253-017-0232-4
PG 8
ER
PT J
AU Gaceb, H
Cherbal, F
Bakour, R
Ould-Rouis, A
Mahfouf, H
AF Gaceb, Hadjer
Cherbal, Farid
Bakour, Rabah
Ould-Rouis, Abdelhalim
Mahfouf, Hassen
TI Clinicopathological and Molecular Study of Triple-Negative Breast Cancer in Algerian Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Algerian women; Breast cancer; Triple negative; Clinicopathological characteristics; BRCA1 mutations; Genetic testing
ID Algerian women; Breast cancer; Triple negative; Clinicopathological characteristics; BRCA1 mutations; Genetic testing
AB Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior, poor prognosis and BRCA1 mutations. There are limited data regarding TNBC among Algerian women. In this study, we sought to determine clinical and tumor characteristics associated with TNBC. We also screened for the prevalence of BRCA1 mutations in unselected cohort of TNBC patients. Clinical and tumor characteristics data of 877 breast cancer patients diagnosed between 2011 and 2015, were collected from cancer registry of public hospital of Rouiba. Patients were divided in two groups: those with TNBC and those with other breast cancer subtypes. Differences between the two groups with regard to clinical and tumor characteristics were compared using Fisher’s exact test. BRCA1 mutations analysis was performed in unselected cohort of 103 women with TNBC, including all exons where a mutation was previously found in Algerian population (exons 2, 3, 5, 11). The median age at diagnosis for TNBC and non- TNBC patients was 47.4 years and 49.4 years, respectively. The proportion of TNBC was 19.95%. Our data showed significant differences in menopausal status, TNM stage, histological type, tumor histological grade, Ki67 expression and family history of breast cancer between TNBC and non- TNBC patients. Four distinct deleterious mutations in BRCA1 gene were detected in eight young TNBC patients. TNBC is associated with young age, poor histopathological characteristics and family history of breast cancer. BRCA1 mutations have been detected in young TNBC patients. TNBC phenotype should be added as criterion to screen for BRCA1 mutations in Algerian women.
C1 [Gaceb, Hadjer] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Cherbal, Farid] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Bakour, Rabah] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Ould-Rouis, Abdelhalim] USTHB, Faculty of Biological Sciences, Laboratory of Dynamics and BiodiversityAlgiers, Algeria.
[Mahfouf, Hassen] University of Algiers, School of Medicine, Public Hospital Academic Medical Oncology ServicesRouiba, Algeria.
RP Cherbal, F (reprint author), USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, 16111 Algiers, Algeria.
EM farid.cherbal@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 297
EP 308
DI 10.1007/s12253-017-0242-2
PG 12
ER
PT J
AU El-Gendi, S
Abu-Sheasha, G
AF El-Gendi, Saba
Abu-Sheasha, Ghada
TI Ki-67 and Cell Cycle Regulators p53, p63 and cyclinD1 as Prognostic Markers for Recurrence/ Progression of Bladder Urothelial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ki-67; cell cycle regulators; Bladder carcinoma; CART; Survival
ID Ki-67; cell cycle regulators; Bladder carcinoma; CART; Survival
AB Deregulation of the cell cycle regulating genes is common in urothelial bladder carcinoma (UBC).We aimed to examine the prognostic significance of ki-67, p53, p63 and cyclinD1expression in UBC and to identify optimal cut-off points to help identifying patients at high risk of tumor recurrence. We evaluated the immunohistochemical expression of ki-67, p53, p63 and cyclinD1 in 100 UBCs. The conventional and the classification and regression trees-guided (CART-guided) methods were utilized to determine the independent predictors of tumor recurrence. The p53 and Ki-67 expression didn’t associate significantly with tumor recurrence.p63 and cyclinD1 exhibited significant hazard ratios. Using CART, no recurrence was observed when p63 was ≥87.5%. The recurrence incidence increased and the disease free survival (DFS) time shortened as the p63 decreased. CyclinD1 associated significantly with tumor recurrence only if p63 was <35%. Using the CART cut-off values¬, cases were categorized into three groups; (groups I: p63 ≥ 35%, II: p63 < 35% and cyclinD1 < 10% and III: p63 < 35% and cyclinD1 ≥ 10%). Group I patients revealed the least incidence of recurrence at the longest DFS. Group III had the worst prognosis followed by Group II. p63 represents a surrogant biomarker to predict UBC recurrence.CyclinD1 can be used only when p63 is <35%. CART proved helpful with data among which the number of cases with positive outcomes is too small relative to the number of studied predictors. Large cohort studies for ki-67 and p53 are recommended to be performed with standardized criteria as regards patients’ characteristics, cut-off values, and follow-up time.
C1 [El-Gendi, Saba] University of Alexandria, Faculty of Medicine, Department of Pathology, 29 Fawzy Moaaz Street, Smouha, 21646 Alexandria, Egypt.
[Abu-Sheasha, Ghada] University of Alexandria, Medical Research Institute, Department of Biomedical Informatics and Medical StatisticsAlexandria, Egypt.
RP El-Gendi, S (reprint author), University of Alexandria, Faculty of Medicine, Department of Pathology, 21646 Alexandria, Egypt.
EM sabaelgendi@yahoo.com
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Sun Z, Tao Y, Li S, Ferguson KK,Meeker JD, Park SK, Batterman SA, Mukherjee B, 2013, Statistical strategies for constructing health risk models with multiple pollutants and their interactions: possible choices and comparisons. Environ Health 12:85
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 309
EP 322
DI 10.1007/s12253-017-0250-2
PG 14
ER
PT J
AU Lee, H
Cho, JH
Park, WJ
Jung, SJ
Choi, IJ
Lee, JH
AF Lee, Hyunsu
Cho, Ji-Hyoung
Park, Won-Jin
Jung, Soo-Jung
Choi, In-Jang
Lee, Jae-Ho
TI Loss of the Association between Telomere Length and Mitochondrial DNA Copy Number Contribute to Colorectal Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Mitochondria DNA copy number; Serrated polyps; Telomere; Tubular adenomas
ID Colorectal cancer; Mitochondria DNA copy number; Serrated polyps; Telomere; Tubular adenomas
AB Positive association between telomere length and mitochondrial DNA (mtDNA) copy number were introduced in healthy and patients with psychiatric disorder. Based on frequent genetic changes of telomere and mitochondria in colorectal carcinomas (CRC), we studied their clinical characteristics and their association in colorectal carcinogenesis. DNA was extracted from 109 CRCs, 64 colorectal tubular adenomas (TAs), and 28 serrated polyps (SPs), and then, telomere length and mtDNA copy number were analyzed in these legions by using a real-time PCR assay. Telomere length and mtDNA copy number (mean ± S.D) in CRCs was 1.87 ± 1.52 and 1.61 ± 1.37, respectively. In TAs and SPs, relative mtDNA copy number was 0.92 ± 0.71 and 1.84 ± 1.06, respectively, shoing statistical difference (p = 0.017). However, telomere length was similar in these precancerous legions. Telomere length and mtDNA copy number did not show clinical and prognostic values in CRCs, however, positive correlation between telomere length and mitochondrial DNA copy number were found in CRC (r = 0.408, p < 0.001). However, this association was not shown in precancerous lesions (r = −0.031, p = 0.765). This result suggests that loss of coregulation between telomeres and mitochondrial function may induce the initiation or play a role as trigger factor of colorectal carcinogenesis.
C1 [Lee, Hyunsu] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Cho, Ji-Hyoung] Keimyung University, School of Medicine, Department of General SurgeryDaegu, South Korea.
[Park, Won-Jin] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Jung, Soo-Jung] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Choi, In-Jang] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
[Lee, Jae-Ho] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeoldaero, Dalseo-Gu, 2800 Daegu, South Korea.
RP Lee, JH (reprint author), Keimyung University, School of Medicine, Department of Anatomy, 2800 Daegu, South Korea.
EM anato82@dsmc.or.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 323
EP 328
DI 10.1007/s12253-017-0245-z
PG 6
ER
PT J
AU Tahmasebi Birgani, M
Hajjari, M
Shahrisa, A
Khoshnevisan, A
Shoja, Z
Motahari, P
Farhangi, B
AF Tahmasebi Birgani, Maryam
Hajjari, Mohammadreza
Shahrisa, Arman
Khoshnevisan, Atefeh
Shoja, Zahra
Motahari, Paria
Farhangi, Baharak
TI Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Biomarker; Long noncoding RNA; SNHG6; Systematic analysis
ID Hepatocellular carcinoma; Biomarker; Long noncoding RNA; SNHG6; Systematic analysis
AB Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer than 200 nucleotides. Their critical roles in different biological pathways have been already well established. Altered expression of lncRNAs can be involved in the cancer initiation and/or progression. Since patients with hepatocellular carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic methods seems to be essential. In this study, the expression levels of different lncRNAs were systematically analysed in different genomic and transcriptome datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive dysregulation of expression and copy number variation in HCC tumors compared with normal tissues. The results also suggest that the dysregulation of SNHG6 is highly cancer type specific. Through co-occurrence analyses, we found that SNHG6 and its related co-expressed genes on 8q are involved in the structural integrity of ribosome and translation. This comprehensive in silico analysis, provides a resource for investigating SNHG6 in hepatocellular carcinoma and lays the groundwork for design of next researches.
C1 [Tahmasebi Birgani, Maryam] Ahvaz Jundishapur University of Medical Sciences, School of Medicine, Department of Medical GeneticsAhvaz, Iran.
[Hajjari, Mohammadreza] Shahid Chamran University of Ahvaz, Faculty of Sciences, Department of GeneticsAhvaz, Iran.
[Shahrisa, Arman] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
[Khoshnevisan, Atefeh] Shahid Chamran University of Ahvaz, Faculty of Sciences, Department of GeneticsAhvaz, Iran.
[Shoja, Zahra] Ahvaz Jundishapur University of Medical Sciences, School of Medicine, Department of Medical GeneticsAhvaz, Iran.
[Motahari, Paria] Iranian Research Organization Science & Technology, Department of BiotechnologyTehran, Iran.
[Farhangi, Baharak] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
RP Tahmasebi Birgani, M (reprint author), Ahvaz Jundishapur University of Medical Sciences, School of Medicine, Department of Medical Genetics, Ahvaz, Iran.
EM tahmasebi-ma@ajums.ac.ir
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Petryszak R, Keays M, Tang YA, Fonseca NA, Barrera E, Burdett T, Fullgrabe A, Fuentes AM-P, Jupp S, Koskinen S, 2015, Expression Atlas update—an integrated database of gene and protein expression in humans, animals and plants. Nucleic Acids Res 44(D1):D746–D752
Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, Huber W, Jupp S, Keays M, Kryvych N, McMurry J, Marioni JC, Malone J, Megy K, Rustici G, Tang AY, Taubert J, Williams E, Mannion O, Parkinson HE, Brazma A, 2014, Expression atlas update–a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments. Nucleic Acids Res 42:D926–D932
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 329
EP 337
DI 10.1007/s12253-017-0241-3
PG 9
ER
PT J
AU Long, H
Guo, X
Qiao, Sh
Huang, Q
AF Long, Houyong
Guo, Xingjun
Qiao, Shen
Huang, Qingxing
TI Tumor LXR Expression is a Prognostic Marker for Patients with Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liver X receptor; Hepatocellular carcinoma; Prognosis; Invasion
ID Liver X receptor; Hepatocellular carcinoma; Prognosis; Invasion
AB Liver X receptor (LXR) activation exerts an antitumor effect. However, whether the tumor LXR expression has prognostic significance in hepatocellular carcinoma (HCC) patient has not been addressed yet. Primary HCC and the adjacent non-tumor tissues were obtained from 169 patients who underwent routine curative surgical treatment. All patients were followed for prognosis analyses. Tumor LXR was detected by immunohistochemical analysis. In in vitro study, several HCC cell lines were cultured for cellular protein detection of LXR and other cytokines, including nuclear factor kappa (NFκB), Matrix metalloproteinases 2 and 9 (MMP- 2 and -9). Meanwhile, the invasion ability of cultured HCC cell lines was performed. We found that LXR expression status in tumor samples is associated with the clinical characteristics, such as tumor stage and metastasis, of HCC patients. Prognosis analysis shows that tumor LXR expression status is closely related to the post-operative outcome in HCC patients who underwent surgical treatment. Patients with low LXR expression have a significantly lower mean 5-year overall survival rate and mean overall survival period than those with high LXR level. Our in vitro data reveal that HCC cell lines had increased NF-κB, MMP2, MMP9 and invasive ability than normal cell line, which are suppressed by LXR activation via NFκB pathway. Our data suggest that LXR could be used as a biomarker for HCC prognosis. Further study is warranted to explore the molecular mechanism under which LXR regulates tumor behaves.
C1 [Long, Houyong] Jining NO.1 People’s Hospital, Department of Hepatobiliary Surgery, 6 Health Street, 272011 Jining, Shandong Province, China.
[Guo, Xingjun] Dongying People’s Hospital, Department of Hepatobiliary Surgery, 257091 Dongying, Shandong Province, China.
[Qiao, Shen] Jining NO.1 People’s Hospital, Department of Hepatobiliary Surgery, 6 Health Street, 272011 Jining, Shandong Province, China.
[Huang, Qingxing] Shanxi Medical University Affiliated Tumor Hospital, Shanxi Tumor Hospital, Department of Digestive Endoscopic and Minimally invasive Surgery, 3 Zhigongxiejie Road, 030013 Taiyuan, Shanxi Province, China.
RP Huang, Q (reprint author), Shanxi Medical University Affiliated Tumor Hospital, Shanxi Tumor Hospital, Department of Digestive Endoscopic and Minimally invasive Surgery, 030013 Taiyuan, China.
EM dr_huang1@163.com;CAOHUANGX@163.COM
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Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA et al, 2004, LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119:299–309
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 339
EP 344
DI 10.1007/s12253-017-0249-8
PG 6
ER
PT J
AU Karai, B
Hevessy, Zs
Szantho, E
Csathy, L
Ujfalusi, A
Gyurina, K
Szegedi, I
Kappelmayer, J
Kiss, Cs
AF Karai, Bettina
Hevessy, Zsuzsanna
Szantho, Eszter
Csathy, Laszlo
Ujfalusi, Aniko
Gyurina, Katalin
Szegedi, Istvan
Kappelmayer, Janos
Kiss, Csongor
TI Expression of Coagulation Factor XIII Subunit A Correlates with Outcome in Childhood Acute Lymphoblastic Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Precursor B-cell acute lymphoblastic leukemia; Immunophenotype; Factor XIII-A; 'B-other' ALL
ID Precursor B-cell acute lymphoblastic leukemia; Immunophenotype; Factor XIII-A; 'B-other' ALL
AB Previously we identified B-cell lineage leukemic lymphoblasts as a new expression site for subunit A of blood coagulation factor XIII (FXIII-A). On the basis of FXIII-A expression, various subgroups of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be identified. Fifty-five children with BCP-ALL were included in the study. Bone marrow samples were obtained by aspiration and the presence of FXIII-A was detected by flow cytometry. G-banding and fluorescent in situ hybridization was performed according to standard procedures. The 10-year event-free survival (EFS) and overall survival (OS) rate of FXIII-A-positive and FXIII-A-negative patients showed significant differences (EFS: 84% vs. 61%, respectively; p = 0.031; OS: 89% vs. 61%; p = 0.008). Of all the parameters examined, there was correlation only between FXIII-A expression and ‘B-other’ genetic subgroup. Further multivariate Cox regression analysis of FXIII-subtype and genetic group or ‘B-other’ subgroup identified the FXIII-A negative characteristic as an independent factor associated with poor outcome in BCP-ALL. We found an excellent correlation between long-term survival and the FXIII-A-positive phenotype of BCP lymphoblasts at presentation. The results presented seem to be convincing enough to suggest a possible role for FXIII-A expression in the prognostic grouping of childhood BCP-ALL patients.
C1 [Karai, Bettina] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Hevessy, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Szantho, Eszter] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Csathy, Laszlo] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Ujfalusi, Aniko] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Gyurina, Katalin] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Szegedi, Istvan] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Kappelmayer, Janos] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt 98, 4032 Debrecen, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, Nagyerdei krt 98, 4032 Debrecen, Hungary.
RP Kiss, Cs (reprint author), University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-Oncology, 4032 Debrecen, Hungary.
EM kisscs@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 345
EP 352
DI 10.1007/s12253-017-0236-0
PG 8
ER
PT J
AU Lawania, Sh
Singh, N
Behera, D
Sharma, S
AF Lawania, Shweta
Singh, Navneet
Behera, Digamber
Sharma, Siddharth
TI XPC Polymorphism and Risk for Lung Cancer in North Indian Patients Treated with Platinum Based Chemotherapy and Its Association with Clinical Outcomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Xeroderma pigmentosum group C; PCR-RFLP; overall survival; Platinum based chemotherapy
ID Lung cancer; Xeroderma pigmentosum group C; PCR-RFLP; overall survival; Platinum based chemotherapy
AB Xeroderma pigmentosum complementation group C plays an important role in the human repair system. As reported in previous studies its polymorphism are associated with lung cancer susceptibility. The purpose of this study is to investigate the association of XPC gene with lung cancer susceptibility, overall response and clinical outcomes amongst North Indians. A hospital based study of 370 lung cancer cases and 370 healthy controls was conducted and genotypes were determined using PCR-RFLP assay. Results were assessed using logistic linear regression adjusted for age, sex and smoking status. Survival analysis was conducted using Kaplan-Meier survival analysis and Cox regression analysis. The treatment outcomes of 167 lung cancer patients treated with platinum based chemotherapy were evaluated.The mutant genotypic variant of XPC Lys939Gln has been associated with elevated risk of lung cancer(OR:2.30;95%CI:1.41-3.73;p=0.0007) whereas XPC Ala499Val showed a highly protective effect (OR:0.25;95%CI:0.10-0.63;p=0.003). The mutant genotype of XPC Lys939Gln presented a higher risk of developing lung cancer in heavy smokers (OR: 3.71; 95%CI:1.46-9.45; p=0.005). The survival analysis presented that heterozygous genotype showed least survival in comparison with mutant genotype in XPC Ala499Val genetic variant whereas no significant association was observed in XPC Lys939Gln. In conclusion, XPC Lys939Gln is associated with significant risk towards the lung cancer whereas on contrary XPC Ala499Val shows a protective effect.
C1 [Lawania, Shweta] Thapar University, Department of Biotechnology, 147002 Punjab, India.
[Singh, Navneet] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary MedicineChandigarh, India.
[Behera, Digamber] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary MedicineChandigarh, India.
[Sharma, Siddharth] Thapar University, Department of Biotechnology, 147002 Punjab, India.
RP Sharma, S (reprint author), Thapar University, Department of Biotechnology, 147002 Punjab, India.
EM siddharthsharma.phd@thapar.edu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 353
EP 366
DI 10.1007/s12253-017-0252-0
PG 14
ER
PT J
AU Yang, Jy
Li, D
Zhang, Y
Guan, Bx
Gao, P
Zhou, Xch
Zhou, Chj
AF Yang, Jing-yan
Li, Dong
Zhang, Yuan
Guan, Bing-xin
Gao, Ping
Zhou, Xing-chen
Zhou, Cheng-jun
TI The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MCM7; Ki67; Intestinal metaplastic; Gastrointestinal epithelial neoplasia
ID MCM7; Ki67; Intestinal metaplastic; Gastrointestinal epithelial neoplasia
AB The aim of this study was to investigate the expression of minichromosome maintenance complex component 7 (MCM7) in gastric mucosal lesions, further to find its potential effect as a biomarker to distinguish intraepithelial neoplasia from gastric mucosal lesions. MCM7 and Ki67 were detected in 93 cases of gastric mucosal lesions by immunohistochemistry. MCM7 and Ki67 expression in GT were lowest compared with other groups (P<0.001), meanwhile there were significant differences compared with Group IM and other groups in MCM7 and Ki67 expression (P<0.001). MCM7 and Ki67 expression in GSC were highest (P<0.05). Groups of LGN, HGN and GIC had no significant differences in MCM7 expression (P>0.05), but there was significant difference compared with Group LGN and Group GIC in Ki67 expression (P<0.05). MCM7 expression elevated with tumor grade increasing and had positive correlation with Ki67 significantly (r=0.940, P<0.001). Furthermore, in some cases, some tumor cells were immunoreactive to MCM7 but negative to Ki67. So we concluded that MCM7 is helpful for us to make differential diagnosis in pathological grade, MCM7 combination of Ki67 may serve as more sensitive proliferation markers for evaluation of gastric carcinoma and precancerous lesions.
C1 [Yang, Jing-yan] The Second Hospital of Shandong University, Department of Pathology, 247#, Bei Yuan Street, 250033 Jinan, Shandong, China.
[Li, Dong] Shandong Provincial Hospital Affiliated to Shandong University, Department of Orthopedics, 324#, Jing 5 Road, 250021 Jinan, Shandong, China.
[Zhang, Yuan] The Second Hospital of Shandong University, Center of Evidence-based Medicine, 247#, Bei Yuan Street, 250033 Jinan, Shandong, China.
[Guan, Bing-xin] The Second Hospital of Shandong University, Department of Pathology, 247#, Bei Yuan Street, 250033 Jinan, Shandong, China.
[Gao, Ping] Yantai Affiliated Hospital of Binzhou Medical University, 717#, Jinbu Road, Muping District, 264100 Yantai, Shandong, China.
[Zhou, Xing-chen] The Second Hospital of Shandong University, Department of Pathology, 247#, Bei Yuan Street, 250033 Jinan, Shandong, China.
[Zhou, Cheng-jun] The Second Hospital of Shandong University, Department of Pathology, 247#, Bei Yuan Street, 250033 Jinan, Shandong, China.
RP Zhou, Chj (reprint author), The Second Hospital of Shandong University, Department of Pathology, 250033 Jinan, China.
EM chengjunzhou@sdu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 367
EP 372
DI 10.1007/s12253-017-0251-1
PG 6
ER
PT J
AU Vosmik, M
Laco, J
Sirak, I
Dvorak, J
Lochman, P
Hodek, M
Mala, P
Rejchrt, S
Repak, R
Lesko, M
Ferko, A
Ryska, A
Melichar, B
Petera, J
AF Vosmik, Milan
Laco, Jan
Sirak, Igor
Dvorak, Josef
Lochman, Petr
Hodek, Miroslav
Mala, Petra
Rejchrt, Stanislav
Repak, Rudolf
Lesko, Michal
Ferko, Alexander
Ryska, Ales
Melichar, Bohuslav
Petera, Jiri
TI Histopathologic Features are more Important Prognostic Factors than Primary Tumour Location in Gastro-oesophageal Adenocarcinoma Treated with Preoperative Chemoradiation and Surgery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Gastro-oesophageal junction cancer; Distal oesophageal cancer; Preoperative chemoradiation; Prognostic factor
ID Gastric cancer; Gastro-oesophageal junction cancer; Distal oesophageal cancer; Preoperative chemoradiation; Prognostic factor
AB The aim of present study was to evaluate the impact of primary tumour location and other factors on the outcome of preoperative chemoradiation followed by surgery in adenocarcinomas of distal oesophagus, gastro-oesophageal junction and stomach. We retrospectively reviewed the institutional patient database. The therapeutic response was re-evaluated as a percentage of residual tumor cells in surgical resection specimens. Overall survival (OS) and disease-free survival (DFS) were assessed. The effect primary tumour location, clinical and pathological TNM stage, and histopathological factors (histological type, grade, angioinvasion, perineural invasion, tumour response) on treatment outcome were evaluated. A total of 108 patients underwent preoperative chemoradiation for adenocarcinoma of distal oesophagus, gastro-oesophageal junction or stomach. The median prescribed dose of radiation was 45 Gy. The concurrent chemotherapy consisted of 5- fluorouracil +/− cisplatin +/− taxanes. R0 resection was achieved in 80 patients (74%). The complete response was observed in 19%. The median follow-up was 50.8 months. Three-year and 5-year OS and DFS were 36.2% and 25.3%; and 28.1% and 23.7%, respectively. Pretreatment T-stage, pathological N-stage, radicality of resection, histological subtype, grade, angioinvasion and perineural invasion, were identified as statistical significant OS predictors in univariate analysis; pathological N-stage, radicality of resection and angioinvasion, in multivariate analysis. The primary tumor location did not influence the prognosis. The pathologic response to chemoradiation had borderline significance. In conclusion, no prognostic impact of primary tumour location, in contrast to other investigated factors, was evident in the present study. The most important predictors of prognosis were angioinvasion status and pN– stage.
C1 [Vosmik, Milan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
[Laco, Jan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Sirak, Igor] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
[Dvorak, Josef] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
[Lochman, Petr] University of Defense, Faculty of Military Health SciencesHradec Kralove, Czech Republic.
[Hodek, Miroslav] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
[Mala, Petra] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
[Rejchrt, Stanislav] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Second Department of Internal Medicine-GastroenterologyHradec Kralove, Czech Republic.
[Repak, Rudolf] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Second Department of Internal Medicine-GastroenterologyHradec Kralove, Czech Republic.
[Lesko, Michal] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of SurgeryHradec Kralove, Czech Republic.
[Ferko, Alexander] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of SurgeryHradec Kralove, Czech Republic.
[Ryska, Ales] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Melichar, Bohuslav] Palacky University, Faculty of Medicine and Dentistry, University Hospital Olomouc, Department of OncologyOlomouc, Czech Republic.
[Petera, Jiri] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and RadiotherapyHradec Kralove, Czech Republic.
RP Vosmik, M (reprint author), Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Hradec Kralove, Czech Republic.
EM milan.vosmik@fnhk.cz
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 373
EP 383
DI 10.1007/s12253-017-0253-z
PG 11
ER
PT J
AU Wang, M
Gao, W
Dehong, L
Teng, L
AF Wang, Miao
Gao, Wei
Dehong, Lu
Teng, Lianghong
TI MiR-1271 Inhibits Cell Growth in Prostate Cancer by Targeting ERG
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; miR-1271; ERG; miR-21
ID Prostate cancer; miR-1271; ERG; miR-21
AB ETS-related gene (ERG) is an oncogene that is commonly found in prostate cancer (PCa). Several miRNAs have been reported to be associated with PCa. This study was undertaken to identify miRNAs that act as a tumor suppressor by targeting ERG. We collected 70 PCa and paired adjacent non-tumor (Adjacent-N) tissues and analyzed ERG expression by immunohistochemistry(IHC). Expression of 6 miRNAs (miR-21,-34a,-96,-125b,-150 and miR-1271) was analyzed by qRT-PCR. Luciferase reporter assay was performed to examine miRNA binding to the 3′-UTR of target genes. The effects of ectopic expression of miRNA on cell growth and MAPK signaling pathway were investigated in in PC-3 and LNCaP cell lines. Among 70 PCa cases, 13 (18.6%) were ERG positive. No significant difference of miR-34a, 96, 125b, and 150 expression was found between PCa and Adjacent-N tissues. Significantly higher level of miR-21 and lower level of miR-1271 expression were found in cancer tissues. Furthermore, miR-1271 was down-regulated in ERG-positive PCa cases (p < 0.05). Based on luciferase reporter assay, we identified ERG gene as a direct target gene for miR-1271. Transfection of a miR-1271 mimics into PC-3 and LNCaP cells repressed the ERG expression and significantly suppressed cell growth. Lastly, ectopic expression of miR-1271 inhibits AKT1, p38gama and CREB kinase activity. Our results suggested that reduced expression of miR- 1271 may be involved in the ERG expression and that miR- 1271 could be a therapeutic target for ERG-positive prostate cancer patients.
C1 [Wang, Miao] Capital Medical University, Basic Medical College, Department of Pathology, No.45 Changchun Street, Xicheng District, 100053 Beijing, China.
[Gao, Wei] Capital Medical University, Xuanwu Hospital, Department of PathologyBeijing, China.
[Dehong, Lu] Capital Medical University, Xuanwu Hospital, Department of PathologyBeijing, China.
[Teng, Lianghong] Capital Medical University, Xuanwu Hospital, Department of PathologyBeijing, China.
RP Teng, L (reprint author), Capital Medical University, Xuanwu Hospital, Department of Pathology, Beijing, China.
EM tenglh2012@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 385
EP 391
DI 10.1007/s12253-017-0254-y
PG 7
ER
PT J
AU Franco, DL
Marrelli, D
Voglino, C
Vindigni, C
Ferrara, F
Mare, DG
Iudici, L
Marini, M
Roviello, F
AF Franco, De Lorenzo
Marrelli, Daniele
Voglino, Costantino
Vindigni, Carla
Ferrara, Francesco
Mare, Di Giulio
Iudici, Livio
Marini, Mario
Roviello, Franco
TI Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Perineural invasion; Lauren histotype; Extended lymphadenectomy; Prognostic factors
ID Gastric cancer; Perineural invasion; Lauren histotype; Extended lymphadenectomy; Prognostic factors
AB The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.
C1 [Franco, De Lorenzo] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Marrelli, Daniele] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Voglino, Costantino] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Vindigni, Carla] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Pathology, 53100 Siena, Italy.
[Ferrara, Francesco] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Mare, Di Giulio] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Iudici, Livio] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
[Marini, Mario] Santa Maria alle Scotte Hospital, Department of Oncology, Unit of gastroenterology and endoscopy, 53100 Siena, Italy.
[Roviello, Franco] University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
RP Marrelli, D (reprint author), University of Siena, Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, 53100 Siena, Italy.
EM marrelli@unisi.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 393
EP 400
DI 10.1007/s12253-017-0257-8
PG 8
ER
PT J
AU Gorka, E
Fabo, D
Gezsi, A
Czirbesz, K
Fedorcsak, I
Liszkay, G
AF Gorka, Eszter
Fabo, Daniel
Gezsi, Andras
Czirbesz, Kata
Fedorcsak, Imre
Liszkay, Gabriella
TI Dabrafenib Therapy in 30 Patients with Melanoma Metastatic to the Brain: a Single-centre Controlled Retrospective Study in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Dabrafenib; Melanoma; Brain metastases; Targeted therapy; BRAF
ID Dabrafenib; Melanoma; Brain metastases; Targeted therapy; BRAF
AB Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0–2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0–2 treated with local therapies and/or chemotherapy, between 2003 and 2015. We found the intracranial disease control rate (DCR) was 83% including four (13%) complete remissions (CR), nine (30%) partial remissions (PR) and twelve (40%) stable diseases (SD) in contrast to five (17%) progressive diseases (PD).With a median follow-up of 14months, median progression-free survival (PFS) and overall survival (OS) were 5.5 months, and 8.8 months, respectively. If calculated from BM onset, the OS turned to be 11.8 months on the dabrafenib arm, while it was only 6.0 months in the control arm (HR = 0.45, p = 0.0014). Higher risk of progression was observed with increasing ECOG (HR =4.06, p = 0.00027) and if more than 2 extracranial organs were involved (HR = 3.4, p = 0.0077). Elevated lactate dehydrogenase (LDH) was non-significantly associated with worse clinical outcome. Remarkable intracranial activity of dabrafenib in real practice was confirmed by our analysis.
C1 [Gorka, Eszter] National Institute of Oncology, Department of Dermatology, Rath Gyorgy str. 7-9, H-1122 Budapest, Hungary.
[Fabo, Daniel] National Institute of Clinical Neurosciences, Amerikai str. 57, H-1145 Budapest, Hungary.
[Gezsi, Andras] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad sq. 4, H-1084 Budapest, Hungary.
[Czirbesz, Kata] National Institute of Oncology, Department of Dermatology, Rath Gyorgy str. 7-9, H-1122 Budapest, Hungary.
[Fedorcsak, Imre] National Institute of Clinical Neurosciences, Amerikai str. 57, H-1145 Budapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of Dermatology, Rath Gyorgy str. 7-9, H-1122 Budapest, Hungary.
RP Gorka, E (reprint author), National Institute of Oncology, Department of Dermatology, H-1122 Budapest, Hungary.
EM goreszter@yahoo.com
CR Falchook GS, Long GV, Kurzrock R et al, 2012, Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose escalation trial. Lancet 379(9829):1893–1901
Long GV, Trefzer U, DaviesMAet al, 2012, Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain, BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 13(11):1087–1095
Dummer R, Goldinger SM, Turtschi CP et al, 2014, Vemurafenib in patients with BRAF(V600, mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J Cancer 50(3):611–621
Colombino M, Capone M, Lissia A et al, 2012, Vemurafenib in patients with BRAF/NRAS mutation frequencies among primary tumours and metastases in patients with melanoma. J Clin Oncol 30(20):2522–2529
Jakob JA, Bassett RL Jr, Ng CS et al, 2012, NRAS mutation status is an independent prognostic factor in metastaticmelanoma. Cancer 118(16):4014–4023
Mittapalli RK, Vaidhyanathan S, Dudek AZ et al, 2013, Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E, inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther 344(3):655–664
Davies MA, Liu P, McIntyre S et al, 2011, Prognostic factors for survival in melanoma patients with brain metastases. Cancer 117(8):1687–1696
Fife KM, Colman MH, Stevens GN et al, 2004, Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol 22(7):1293–1300
Sampson JH, Carter JH Jr, Friedman AH et al, 1998, Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88(1):11–20
Dzienis MR, Atkinson V., 2013, Response rate to vemurafenib in BRAF-positive melanoma brain metastases. J Clin Oncol 31, abstract 9081
Harding JJ, Catalanotti F, Munhoz RR et al, 2015, A retrospective evaluation of Vemurafenib as treatment for BRAF-mutant melanoma brain metastases. Oncologist 20(7):789–797
Azer MW, Menzies AM, Haydu LE et al, 2014, Patterns of response and progression in patients with BRAF-mutant melanoma metastatic to the brain who were treated with dabrafenib. Cancer 120(4):530–536
Cocorocchio E, Gandini S, Alfieri S et al, 2016, Dabrafenib in metastatic melanoma: a monocentric 'real life' experience. Ecancermedicalscience 10:624
Lau DK, Andrews MC, Turner N et al, 2014, A single-centre experience of patients with metastatic melanoma enrolled in a dabrafenib named patient programme. Mel res 24(2):144–149
Hauschild A, Grob JJ, Demidov LV et al, 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, openlabel, phase 3 randomised controlled trial. Lancet 380(9839): 358–365
Long GV, Stroyakovskiy D, Gogas H et al, 2014, Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J med 371(20):1877–1888
Schadendorf D, Amonkar MM, Stroyakovskiy D et al, 2015, Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer 51(7):833–840
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 401
EP 406
DI 10.1007/s12253-017-0256-9
PG 6
ER
PT J
AU da Silva, NG
Filoni, TL
Salvadori, CM
Favero Salvadori, MD
AF da Silva, Nicioli Glenda
Filoni, Toshio Leandro
Salvadori, Cecilia Maria
Favero Salvadori, Maria Daisy
TI Gemcitabine/Cisplatin Treatment Induces Concomitant SERTAD1, CDKN2B and GADD45A Modulation and Cellular Changes in Bladder Cancer Cells Regardless of the Site of TP53 Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Cell morphology; Chemotherapy; Cisplatin; Gene expression; Gemcitabine
ID Bladder cancer; Cell morphology; Chemotherapy; Cisplatin; Gene expression; Gemcitabine
AB Simultaneous use of cisplatin (CIS) and gemcitabine (GEN) for treating bladder cancer has increased because of their complementary effects. However, the molecular mechanisms underlying the activities of these two antineoplastic drugs are not fully known. Here, molecular biology techniques and microscopy were used to investigate transcriptomic and morphological changes in low and highgrade urinary bladder transitional carcinoma cell lines [RT4 - wild type TP53; 5637 - two TP53 mutations, one in codon 72 (Arg-Pro) and other in codon 280 (Arg-Thr) and T24 - inframe deletion of tyrosine 126 in the TP53 allele] simultaneously treated with CIS/GEN. Gene expression profile was evaluated by PCR arrays; cell morphology by scanning and transmission electron microscopy, and apoptosis was analyzed using fluorescent dye. Results showed concomitantly upregulation of CDKN2B (G1/S transition), GADD45A (DNA repair and apoptosis) and SERTAD1 (regulation of transcription) gene, increased number of nuclear chamfers and apoptotic cells, and reduced number of microfilaments, organelles and in the size of the nucleus in 5637 and T24 cells after simultaneous treatment with CIS/GEN. In conclusion, independently of the TP53 mutation status and tumor grade, CIS/ GEN induced gene modulation accompanied by changes in cell morphologies, which confirm the antiproliferative activity of the treatment protocol. These findings help to understand the pathways modulated by these antineoplastic agents and may provide insights for anti-cancer chemotherapy.
C1 [da Silva, Nicioli Glenda] UFOP – Federal University of Ouro Preto, School of PharmacyOuro Preto, MG, Brazil.
[Filoni, Toshio Leandro] USP – University of Sao Paulo, Institute of PhysicsSao Paulo, SP, Brazil.
[Salvadori, Cecilia Maria] USP – University of Sao Paulo, Institute of PhysicsSao Paulo, SP, Brazil.
[Favero Salvadori, Maria Daisy] UNESP – State University of Sao Paulo, Medical SchoolBotucatu, SP, Brazil.
RP da Silva, NG (reprint author), UFOP – Federal University of Ouro Preto, School of Pharmacy, Ouro Preto, Brazil.
EM nicioli@ef.ufop.br
CR von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T et al, 2005, Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608., DOI 10.1200/JCO.2005.07.757
Yuh BE, Ruel N, Wilson TG, Vogelzang N, Pal SK, 2013, Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer. J Urol 189:1682–1686., DOI 10.1016/j.juro.2012.10.120
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Da Silva GN, de Camargo EA, Salvadori DM, 2012, Toxicogenomic activity of gemcitabine in two TP53-mutated bladder cancer cell lines: special focus on cell cycle-related genes. Mol Biol rep 39(12):10373–10382., DOI 10.1007/s11033-012-1916-1
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 407
EP 417
DI 10.1007/s12253-017-0255-x
PG 11
ER
PT J
AU Zhu, FF
Zheng, FY
Wang, HO
Zheng, JJ
Zhang, Q
AF Zhu, Fang-Fang
Zheng, Fei-Yun
Wang, Hai-Ou
Zheng, Jing-Jie
Zhang, Qian
TI Downregulation of lncRNA TUBA4B is Associated with Poor Prognosis for Epithelial Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; lncRNA; Overall survival; Proliferation
ID Ovarian cancer; lncRNA; Overall survival; Proliferation
AB A host of studies have revealed that long noncoding RNAs (lncRNAs) are critically involved in the development and progression of epithelial ovarian cancer. LncRNA TUBA4B is recently identified to be a critical mediator in nonsmall cell lung cancer. However, the clinical roles and biological functions of lncRNA TUBA4B in epithelial ovarian cancer have yet to be fully clarified. The present study was conducted to explore the expression of lncRNA TUBA4B in human epithelial ovarian cancer tissues and potential roles of lncRNA TUBA4B in ovarian cancer cells. The matched epithelial ovarian cancer specimens and adjacent normal tissues were employed to detect the expression of lncRNA TUBA4B. The prognostic value of lncRNA TUBA4B for tumor progression and survival rate was investigated. The effects of lncRNA TUBA4B on ovarian cancer cell proliferation and migration were also explored. The expression of lncRNA TUBA4B was significantly decreased in epithelial ovarian cancer tissue specimens. The low lncRNA TUBA4B level was closely related with pathological grade, FIGO stage and lymph node metastases, and serum CA125 level. Enforced expression of lncRNA TUBA4B obviously reduced the proliferation of SKOV3 cells, and attenuated the activation of ERK and Akt signaling pathways. Our data demonstrate for the first time that lower lncRNA TUBA4B may be a novel independent prognostic biomarker for overall survival of epithelial ovarian cancer. Overexpression of lncRNA TUBA4B inhibits the proliferation of ovarian cancer cells. LncRNA TUBA4B may be an important target for therapeutic intervention in ovarian cancer.
C1 [Zhu, Fang-Fang] the First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology, 1 Fuxue Lane, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Zheng, Fei-Yun] the First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology, 1 Fuxue Lane, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Wang, Hai-Ou] the First Affiliated Hospital of Wenzhou Medical University, Department of Obstetrics and GynecologWenzhou, Zhejiang, China.
[Zheng, Jing-Jie] the First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology, 1 Fuxue Lane, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Zhang, Qian] the First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology, 1 Fuxue Lane, Lucheng District, 325000 Wenzhou, Zhejiang, China.
RP Zhang, Q (reprint author), the First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology, 325000 Wenzhou, China.
EM qianzhangwzzj@yeah.net
CR Ross JS, Ali SM,Wang K, Palmer G, Yelensky R, Lipson D,Miller VA, Zajchowski D, Shawver LK, Stephens PJ, 2013, Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies. Gynecol Oncol 130(3):554–559., DOI 10.1016/j.ygyno.2013.06.019
Chudecka-Glaz AM, 2015, ROMA, an algorithm for ovarian cancer. Clinica chimica acta; international journal of clinical chemistry 440:143–151., DOI 10.1016/j.cca.2014.11.015
Su Y, Wu H, Pavlosky A, Zou LL, Deng X, Zhang ZX, Jevnikar AM, 2016, Regulatory non-coding RNA: new instruments in the orchestration of cell death. Cell Death Dis 7(8):e2333., DOI 10.1038/ cddis.2016.210
Li F, Hu CP, 2015, Long non-coding RNA Urothelial carcinoma associated 1, UCA1): insight into its role in human diseases. Crit Rev Eukaryot Gene Expr 25(3):191–197
Chen J, Hu L, Wang J, Zhang F, Chen J, Xu G, Wang Y, Pan Q, 2017, Low expression LncRNA TUBA4B is a poor predictor of prognosis and regulates cell proliferation in non-small cell lung cancer. Pathology Oncology Research: POR 23(2):265-270.doi: 10.1007/s12253-016-0089-y
Sun HJ, Liu TY, Zhang F, Xiong XQ, Wang JJ, Chen Q, Li YH, Kang YM, Zhou YB, Han Y, Gao XY, Zhu GQ, 2015, Salusin-beta contributes to vascular remodeling associated with hypertension via promoting vascular smooth muscle cell proliferation and vascular fibrosis. BiochimBiophys Acta 1852(9):1709–1718., DOI 10.1016/j. bbadis.2015.05.008
Sun HJ, Zhao MX, Ren XS, Liu TY, Chen Q, Li YH, Kang YM, Wang JJ, Zhu GQ, 2016, Salusin-beta promotes vascular smooth muscle cell migration and intimal hyperplasia after vascular injury via ROS/NFkappaB/MMP-9 pathway. Antioxid Redox Signal 24(18):1045–1057., DOI 10.1089/ars.2015.6475
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA Cancer J Clin 61(2):69–90., DOI 10. 3322/caac.20107
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Yang Y, Jiang Y,Wan Y, Zhang L, Qiu J, Zhou S, ChengW(2016, UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis. Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine 37(8):10633–10641., DOI 10.1007/s13277-016-4917-1
Gao Y, Meng H, Liu S, Hu J, Zhang Y, Jiao T, Liu Y, Ou J,Wang D, Yao L, Liu S, Hui N, 2015, LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b. Hum Mol Genet 24(3):841–852., DOI 10.1093/hmg/ddu502
Qiu JJ, Lin YY, Ye LC, Ding JX, FengWW, Jin HY, ZhangY, Li Q, Hua KQ, 2014)Overexpression of long non-codingRNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol 134(1):121–128., DOI 10. 1016/j.ygyno.2014.03.556
Wang L, Wang J, Fang J, Zhou H, Liu X, Su SB, 2015, High glucose induces and activates toll-like receptor 4 in endothelial cells of diabetic retinopathy. Diabetol Metab Syndr 7:89., DOI 10.1186/ s13098-015-0086-4
Hu X, Sun S, 2015, RAD51 Gene 135G/C polymorphism and ovarian cancer risk: a meta-analysis. Int J Clin Exp Med 8(12): 22365–22370
Liu X, Li G, 2015, MicroRNA-133b inhibits proliferation and invasion of ovarian cancer cells through Akt and Erk1/2 inactivation by targeting epidermal growth factor receptor. Int J Clin Exp Pathol 8(9):10605–10614
Huang WL, Li Z, Lin TY, Wang SW, Wu FJ, Luo CW, 2016, Thyrostimulin-TSHR signaling promotes the proliferation of NIH: OVCAR-3 ovarian cancer cells via trans-regulation of the EGFR pathway. Sci Report 6:27471., DOI 10.1038/srep27471
Dong YL, Kabir SM, Lee ES, Son DS, 2013, CXCR2-driven ovarian cancer progression involves upregulation of proinflammatory chemokines by potentiating NF-kappaB activation via EGFRtransactivated Akt signaling. PLoS One 8(12):e83789., DOI 10. 1371/journal.pone.0083789
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 419
EP 425
DI 10.1007/s12253-017-0258-7
PG 7
ER
PT J
AU Karbyshev, SM
Grigoryeva, SE
Volkomorov, VV
Kremmer, E
Huber, A
Mitrofanova, VI
Kaigorodova, VE
Zavyalova, VM
Kzhyshkowska, GJ
Cherdyntseva, VN
Choynzonov, LE
AF Karbyshev, S Mikhail
Grigoryeva, S Evgeniya
Volkomorov, V Viktor
Kremmer, Elisabeth
Huber, Alexander
Mitrofanova, V Irina
Kaigorodova, V Evgeniya
Zavyalova, V Marina
Kzhyshkowska, G Julia
Cherdyntseva, V Nadezda
Choynzonov, L Evgeny
TI Development of Novel Monoclonal Antibodies for Evaluation of Transmembrane Prostate Androgen-Induced Protein 1 (TMEPAI) Expression Patterns in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Monoclonal antibody; Biomarker; Immunohistochemistry; Gastric cancer; PMEPA1; TMEPAI
ID Monoclonal antibody; Biomarker; Immunohistochemistry; Gastric cancer; PMEPA1; TMEPAI
AB Transmembrane prostate androgen-induced protein 1 (TMEPAI) is a single-span membrane protein, functionally involved in transforming growth factor beta signaling pathway. The particular protein presented in cells in three isoforms, which differs in the length of the soluble N-terminal extracellular domain, making it challenging for the immunochemical recognition. By using quantitative real-time polymerase chain reaction, we identified significant upregulation of PMEPA1 gene expression in malignant tissues of patients with gastric adenocarcinoma. The main part of commercially available anti-TMEPAI antibodies are having polyclonal nature or not suitable for immunocytochemical localization of target protein in tissue specimens. Hence, we decide to generate a set of novel rat monoclonal antibodies (mAb) directed against conservative C-terminal cytoplasmic epitope. Immunoblotting analysis showed that monoclonal antibodies, 2E1, 6C6, and 10A7 were able to recognize specifically target protein in transiently transfected HEK293T and CHO-K1 cells. Especially established mAb, named 10A7, showed the excellent binding ability to target protein in immunohistochemistry. By using developed antibodies, we observed pronounced expression of TMEPAI in normal gastric epithelial cells while tumor cells from gastric adenomas, and adenocarcinoma samples were mostly negative for target protein expression. Also, we found that gastric epithelium cells lose the TMEPAI expression concurrently with severe dysplasia progression, which probably caused by a mechanism involving specific microRNA.
C1 [Karbyshev, S Mikhail] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Grigoryeva, S Evgeniya] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Volkomorov, V Viktor] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Kremmer, Elisabeth] Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Institute of Molecular Immunology, Marchionini str. 25, 81377 Munich, Germany.
[Huber, Alexander] Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Institute of Molecular Immunology, Marchionini str. 25, 81377 Munich, Germany.
[Mitrofanova, V Irina] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Kaigorodova, V Evgeniya] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Pathological Anatomy and Cytology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Zavyalova, V Marina] Tomsk State University, Laboratory for Translational Cellular and Molecular Biomedicine, 36 Lenin Ave, 634050 Tomsk, Russian Federation.
[Kzhyshkowska, G Julia] Tomsk State University, Laboratory for Translational Cellular and Molecular Biomedicine, 36 Lenin Ave, 634050 Tomsk, Russian Federation.
[Cherdyntseva, V Nadezda] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
[Choynzonov, L Evgeny] Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, Kooperativny Str. 5, 634050 Tomsk, Russian Federation.
RP Grigoryeva, SE (reprint author), Russian Academy of Sciences, Cancer Research Institute, Tomsk National Research Medical Center, Department of Molecular Oncology and Immunology, 634050 Tomsk, Russian Federation.
EM grigorieva@oncology.tomsk.ru
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 427
EP 438
DI 10.1007/s12253-017-0247-x
PG 12
ER
PT J
AU Shinmura, K
Kato, H
Kawanishi, Y
Kamo, T
Inoue, Y
Yoshimura, K
Sugiyama, K
Misawa, K
Hosokawa, S
Mineta, H
Sugimura, H
AF Shinmura, Kazuya
Kato, Hisami
Kawanishi, Yuichi
Kamo, Takaharu
Inoue, Yusuke
Yoshimura, Katsuhiro
Sugiyama, Kenta
Misawa, Kiyoshi
Hosokawa, Seiji
Mineta, Hiroyuki
Sugimura, Haruhiko
TI BSND is a Novel Immunohistochemical Marker for Oncocytic Salivary Gland Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BSND; Immunohistochemical marker; Oncocytic salivary gland tumor; Oncocytoma; Warthin’s tumor
ID BSND; Immunohistochemical marker; Oncocytic salivary gland tumor; Oncocytoma; Warthin’s tumor
AB BSND protein, which is involved in chloride transport, is expressed in normal kidney and the inner ear and is known as an immunohistochemical marker for chromophobe renal cell carcinoma (RCC) and renal oncocytoma; however, other organs and tumor types exhibiting BSND expression have not yet been reported. In this study, we investigated the expression of BSND using data from the Cancer Genome Atlas (TCGA) database and by performing immunohistochemical analyses. As a result, we found that BSND was also expressed in the striated duct cells of normal salivary glands. Next, BSND expression was examined immunohistochemically in 7 types of salivary gland tumors, and BSND positivity was found in Warthin’s tumor (25 out of 25 cases; 100%) and oncocytoma (4/4; 100%), both of which are usually classified as oncocytic tumors, whereas BSND negativity was observed for pleomorphic adenoma (0/11), adenoid cystic carcinoma (0/7), acinic cell carcinoma (0/6), mucoepidermoid carcinoma (0/6), and salivary duct carcinoma (0/5). Finally, the expression of BSND mRNA in 30 types of tumors other than chromophobe RCC and salivary gland tumors was examined using data from the TCGA database, but none of these tumors exhibited BSND expression. These results suggest that BSND is expressed only in normal salivary glands and oncocytic salivary gland tumors such as Warthin’s tumor and oncocytoma in addition to the two known organs and the two known renal tumor types mentioned above. The selective expression pattern of BSND suggests that BSND is an excellent novel immunohistochemical marker for oncocytic salivary gland tumors.
C1 [Shinmura, Kazuya] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Kato, Hisami] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Kawanishi, Yuichi] Hamamatsu University School of Medicine, Preeminent Medical Photonics Education and Research CenterHamamatsu, Japan.
[Kamo, Takaharu] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Inoue, Yusuke] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Yoshimura, Katsuhiro] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Sugiyama, Kenta] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
[Misawa, Kiyoshi] Hamamatsu University School of Medicine, Department of Otolaryngology / Head and Neck SurgeryHamamatsu, Japan.
[Hosokawa, Seiji] Hamamatsu University School of Medicine, Department of Otolaryngology / Head and Neck SurgeryHamamatsu, Japan.
[Mineta, Hiroyuki] Hamamatsu University School of Medicine, Department of Otolaryngology / Head and Neck SurgeryHamamatsu, Japan.
[Sugimura, Haruhiko] Hamamatsu University School of Medicine, Department of Tumor Pathology, 1-20-1 Handayama, Higashi Ward, 431-3192 Hamamatsu, Japan.
RP Shinmura, K (reprint author), Hamamatsu University School of Medicine, Department of Tumor Pathology, 431-3192 Hamamatsu, Japan.
EM kzshinmu@hama-med.ac.jp
CR Estevez R, Boettger T, Stein V et al, 2001, Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature 414:558–561
Birkenhager R, Otto E, Schurmann MJ et al, 2001, Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet 29:310–314
Shinmura K, Igarashi H, Kato H et al, 2015, BSNDand ATP6V1G3: novel Immunohistochemical markers for Chromophobe renal cell carcinoma. Medicine, Baltimore, 94:e989
Barnes L, Eveson JW, Reichart P, Sidransky D, 2005)World Health Organization classification of tumors: pathology and genetics of the head and neck Tumours. IARC Press, Lyon
Nagao T, Sato E, Inoue R et al, 2012, Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem 45:269–282
Ellis GL, Auclair PL, 2008, Tumors of the salivary glands, AFIP atlas of tumor pathology: series 4, book 9). American Registry of Pathology, Washington, DC
Shintaku M, Honda T, 1997, Identification of oncocytic lesions of salivary glands by anti-mitochondrial immunohistochemistry. Histopathology 31:408–411
Foschini MP, Marucci G, Eusebi V, 2002, Low-grade mucoepidermoid carcinoma of salivary glands: characteristic immunohistochemical profile and evidence of striated duct differentiation. Virchows Arch 440:536–542
Akai A, Yamamura Y, Nonaka M et al, 2014, 99mTcO4− accumulation in scintigraphy and expression of Na+/I− symporter in salivary gland tumors. Auris Nasus Larynx 41:532–538
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 439
EP 444
DI 10.1007/s12253-017-0248-9
PG 6
ER
PT J
AU Masood, N
Basharat, Z
Khan, T
Yasmin, A
AF Masood, Nosheen
Basharat, Zarrin
Khan, Tabeer
Yasmin, Azra
TI Erratum to: Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with Various Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Erratum to: Pathol. Oncol. Res. DOI 10.1007/s12253-016-0184-0 The original version of this article unfortunately contained an error in the author group section. The author group should have been Nosheen Masood, Zarrin Basharat, Tabeer Khan and Azra Yasmin instead of Nosheen Masood & Azra Yasmin. The corrected author group is shown above.
C1 [Masood, Nosheen] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Basharat, Zarrin] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Khan, Tabeer] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
[Yasmin, Azra] Fatima Jinnah Women University, The MallRawalpindi, Pakistan.
RP Masood, N (reprint author), Fatima Jinnah Women University, The Mall, Rawalpindi, Pakistan.
EM nosheenmasood@hotmail.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2018
VL 24
IS 2
BP 445
EP 445
DI 10.1007/s12253-016-0184-0
PG 1
ER
PT J
AU Massari, F
Ciccarese, Ch
Hes, O
Michal, M
Calio, A
Fiorentino, M
Giunchi, F
D’Amuri, A
Sanguedolce, F
Sabbatini, R
Guida, A
Ardizzoni, A
Porta, C
Iacovelli, R
Tortora, G
Cima, L
Ortega, C
Lapini, A
Martignoni, G
Brunelli, M
AF Massari, Francesco
Ciccarese, Chiara
Hes, Ondrej
Michal, Michal
Calio, Anna
Fiorentino, Michelangelo
Giunchi, Francesca
D’Amuri, Alessandro
Sanguedolce, Francesca
Sabbatini, Roberto
Guida, Annalisa
Ardizzoni, Andrea
Porta, Camillo
Iacovelli, Roberto
Tortora, Giampaolo
Cima, Luca
Ortega, Cinzia
Lapini, Alberto
Martignoni, Guido
Brunelli, Matteo
TI The Tumor Entity Denominated "clear cell-papillary renal cell carcinoma" According to the WHO 2016 new Classification, have the Clinical Characters of a Renal Cell Adenoma as does Harbor a Benign Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Clear cell papillary RCC; Renal adenomatoid tumour (RAT); WHO 2016 classification of renal neoplasia; Renal adenoma; Benign
ID Clear cell papillary RCC; Renal adenomatoid tumour (RAT); WHO 2016 classification of renal neoplasia; Renal adenoma; Benign
AB The new WHO 2016 classification of renal neoplasia encounters the new entity called "clear cell papillary renal cell carcinoma" (ccpRCC). The ccpRCC has been long included as a subtype of clear cell RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.
C1 [Massari, Francesco] S.Orsola-Malpighi Hospital, Division of OncologyBologna, Italy.
[Ciccarese, Chiara] AOUI, University of Verona, Division of OncologyVerona, Italy.
[Hes, Ondrej] Charles University, Faculty of Medicine in Plzen, Department of PathologyPilsen, Czech Republic.
[Michal, Michal] Charles University, Faculty of Medicine in Plzen, Department of PathologyPilsen, Czech Republic.
[Calio, Anna] AOUI, University of Verona, Department of Diagnostics and Public HealthVerona, Italy.
[Fiorentino, Michelangelo] S.Orsola-Malpighi Hospital, Department of PathologyBologna, Italy.
[Giunchi, Francesca] S.Orsola-Malpighi Hospital, Department of PathologyBologna, Italy.
[D’Amuri, Alessandro] Card. G. Panico Hospital, Anatomic PathologyLecce, Italy.
[Sanguedolce, Francesca] University of Foggia, Department of PathologyFoggia, Italy.
[Sabbatini, Roberto] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Guida, Annalisa] University of Modena & Reggio Emilia, Department of Oncology, Hematology & Respiratory DiseasesModena, Italy.
[Ardizzoni, Andrea] S.Orsola-Malpighi Hospital, Division of OncologyBologna, Italy.
[Porta, Camillo] I.R.C.C.S. San Matteo University Hospital Foundation, Division of OncologyPavia, Italy.
[Iacovelli, Roberto] AOUI, University of Verona, Division of OncologyVerona, Italy.
[Tortora, Giampaolo] AOUI, University of Verona, Division of OncologyVerona, Italy.
[Cima, Luca] AOUI, University of Verona, Department of Diagnostics and Public HealthVerona, Italy.
[Ortega, Cinzia] Asl Cn2 Alba-Bra, Institute for Cancer Research and Treatment, Division of OncologyPiemonte, Italy.
[Lapini, Alberto] University of Florence, Carreggi Hospital, Urology Clinic, Peschiera del GardaFlorence, Italy.
[Martignoni, Guido] AOUI, University of Verona, Department of Diagnostics and Public HealthVerona, Italy.
[Brunelli, Matteo] AOUI, University of Verona, Department of Diagnostics and Public HealthVerona, Italy.
RP Brunelli, M (reprint author), AOUI, University of Verona, Department of Diagnostics and Public Health, Verona, Italy.
EM matteo.brunelli@univr.it
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 447
EP 456
DI 10.1007/s12253-017-0271-x
PG 10
ER
PT J
AU Lopez-Cortes, A
Cabrera-Andrade, A
Ona-Cisneros, F
Echeverria, C
Rosales, F
Ortiz, M
Tejera, E
Paz-y-Mino, C
AF Lopez-Cortes, Andres
Cabrera-Andrade, Alejandro
Ona-Cisneros, Fabian
Echeverria, Carolina
Rosales, Felipe
Ortiz, Malena
Tejera, Eduardo
Paz-y-Mino, Cesar
TI Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; AURKA; Ecuadorianpopulation; Genotyping; High altitude; Mestizo
ID Breast cancer; AURKA; Ecuadorianpopulation; Genotyping; High altitude; Mestizo
AB Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective casecontrol study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4–4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6–9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6–5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0–91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7–101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).
C1 [Lopez-Cortes, Andres] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Cabrera-Andrade, Alejandro] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Ona-Cisneros, Fabian] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Echeverria, Carolina] Ministerio de Salud Publica, Direccion Nacional de Inteligencia de la Salud, Avenue Republica de El Salvador, 170515 Quito, Ecuador.
[Rosales, Felipe] Hospital Oncologico Solon Espinosa Ayala, Departamento de Patologia, Avenue Eloy Alfaro, 170138 Quito, Ecuador.
[Ortiz, Malena] Ministerio de Salud Publica del Ecuador, Hospital General Docente de Calderon, Avenue Capitan Giovanni Calles, 170206 Quito, Ecuador.
[Tejera, Eduardo] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Paz-y-Mino, Cesar] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
RP Lopez-Cortes, A (reprint author), Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, 170129 Quito, Ecuador.
EM aalc84@gmail.com
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Lopez-Cortes A, Jaramillo-Koupermann G, MunozMJ, Cabrera A, Echeverria C, Rosales F, Vivar N, Paz-y-Mino C, 2013, Genetic polymorphisms in MTHFR, C677T, A1298C), MTR, A2756G, andMTRR, A66G, genes associated with pathological characteristics of prostate cancer in the Ecuadorian population. Am J Med Sci 346:447–454
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Quinones LA, Lavanderos MA, Cayun JP, Garcia-Martin E, Agundez JA, Caceres DD, Roco AM, Morales JE, Herrera L, Encina G, Isaza CA, Redal MA, Larovere L, Soria NW, Eslava- Schmalbach J, Castaneda-Hernandez G, Lopez-Cortes A, Magno LA, LopezM, Chiurillo MA, Rodeiro I, Castro de Guerra D, Teran E, Estevez-Carrizo F, Lares Assef I, 2014, Perception of the usefulness of drug/gene pairs and barriers for pharmacogenomics in Latin America. Curr Drug Metab 15:202–208 52 Lopez-Cortes A, Guerrero S, Redal M, Alvarado A, Quinones L, 2017, State of Art of Cancer Pharmacogenomics in Latin American Populations. Int J Mol Sci 18(6):639
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 457
EP 465
DI 10.1007/s12253-017-0267-6
PG 9
ER
PT J
AU Lopez-Cortes, A
Cabrera-Andrade, A
Ona-Cisneros, F
Echeverria, C
Rosales, F
Ortiz, M
Tejera, E
Paz-y-Mino, C
AF Lopez-Cortes, Andres
Cabrera-Andrade, Alejandro
Ona-Cisneros, Fabian
Echeverria, Carolina
Rosales, Felipe
Ortiz, Malena
Tejera, Eduardo
Paz-y-Mino, Cesar
TI Erratum to: Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Erratum to: Pathol. Oncol. Res. https://doi.org/10.1007/s12253-017-0275-6 Unfortunately, the name of the fourth author Carolina Echeverria and her corresponding affiliation 2 were missing in the published online paper. The corrected author group is shown above and the corrected affiliation is shown below.
C1 [Lopez-Cortes, Andres] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Cabrera-Andrade, Alejandro] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Ona-Cisneros, Fabian] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
[Echeverria, Carolina] Ministerio de Salud Publica, Direccion Nacional de Inteligencia de la Salud, Avenue Republica de El Salvador, 170515 Quito, Ecuador.
[Rosales, Felipe] Hospital Oncologico Solon Espinosa Ayala, Departamento de Patologia, Avenue Eloy Alfaro, 170138 Quito, Ecuador.
[Ortiz, Malena] Ministerio de Salud Publica del Ecuador, Hospital General Docente de Calderon, Avenue Capitan Giovanni Calles, 170206 Quito, Ecuador.
[Tejera, Eduardo] Universidad de las Americas, Facultad de Ciencias de la Salud, Avenue de los Granados, 170125 Quito, Ecuador.
[Paz-y-Mino, Cesar] Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
RP Lopez-Cortes, A (reprint author), Universidad Tecnologica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigacion Genetica y Genomica, 170129 Quito, Ecuador.
EM aalc84@gmail.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 467
EP 467
DI 10.1007/s12253-017-0299-y
PG 1
ER
PT J
AU Helbig, G
Koclega, A
Wozniczka, K
Kopera, M
Kyrcz-Krzemien, S
AF Helbig, Grzegorz
Koclega, Anna
Wozniczka, Krzysztof
Kopera, Malgorzata
Kyrcz-Krzemien, Slawomira
TI Long-Term Outcome of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Acute Myeloid Leukemia (AML)- Single Center Retrospective Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute myeloid leukemia; Autologous hematopoietic stem cell transplantation; Relapse; Outcome
ID Acute myeloid leukemia; Autologous hematopoietic stem cell transplantation; Relapse; Outcome
AB For patients with acute myeloid leukemia (AML) in complete remission without an acceptable HLA donor, the autologous hematopoietic stem cell transplantation (AHSCT) may remain a therapeutic option as remission consolidation, however its role is still a subject of continued debate. One hundred and twenty patients who underwent AHSCT for AML were included in this retrospective single center analysis. The procedure was performed over a 19 years period and transplanted patients were in first complete remission (CR1; n = 109) or in second CR (CR2; n = 11). The median age at transplant was 37 years (range 18–64). The source of stem cells was bone marrow (n = 61; 50.8%), peripheral blood (n = 36; 30%) and bone marrow with peripheral blood (n = 23; 19.2%). The median time from AML diagnosis to AHSCT was 0.8 year (range 0.3–4.4) and the median follow-up after AHSCT for surviving patients was 12.8 years (range 3.1–20.5). The median LFS was 1.1 year. The probability of LFS calculated at 5 years and 10 years after transplantation was 28% (95% CI, 22%–32%) and 21% (95% CI, 18%–24%), respectively. The last relapse occurred 14.8 years after AHSCT and among patients who survived >2 years, 28.4% (27/95) had leukemia recurrence. The median OS was 1.7 years. The probability of OS after 5 years and 10 years was 29% and 22%, respectively. There was a tendency for increased LFS for patients younger than 50 years at transplant if compared to older population. AHSCT for AML was safe with acceptable toxicity profile. Leukemia recurrence remained the leading cause of death.
C1 [Helbig, Grzegorz] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street 25, 40-032 Katowice, Poland.
[Koclega, Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street 25, 40-032 Katowice, Poland.
[Wozniczka, Krzysztof] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street 25, 40-032 Katowice, Poland.
[Kopera, Malgorzata] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street 25, 40-032 Katowice, Poland.
[Kyrcz-Krzemien, Slawomira] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street 25, 40-032 Katowice, Poland.
RP Helbig, G (reprint author), Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, 40-032 Katowice, Poland.
EM ghelbig@o2.pl
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Czerw T, Labopin M, Gorin NC et al, 2016, Long-term follow-up of patients with acute myeloid leukemia surviving and free of disease recurrence for at least 2 years after autologous stem cell transplantation: a report from the acute leukemia working Party of the European Society for blood and marrow Transplnatation. Cancer 122:1880–1887
Zuckerman T, Beyar-Katz O, Rowe JM, 2016, Should autotranplantation in acute myeloid leukemia in first complete remission be revisited. Curr Opin Hematol 23:88–94
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Vellenga E, van Putten W, Ossenkoppele GJ et al, 2011, Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood 118:6037–6042
Cornelissen JJ, Versluis J, Passweg JR et al, 2015, Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years. Leukemia 29:1041–1050
Keating A, DaSilva G, Perez WS et al, 2013, Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Haematologica 98:185–192
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 469
EP 475
DI 10.1007/s12253-017-0266-7
PG 7
ER
PT J
AU Lee, HJ
Song, YS
Kim, SM
Yoo, JN
Lee, HS
AF Lee, Hwa Ju
Song, Yong Sang
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GLI1; Frameshift mutation; Colon cancer; Microsatellite instability; Intratumoral heterogeneity
ID GLI1; Frameshift mutation; Colon cancer; Microsatellite instability; Intratumoral heterogeneity
AB GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing. We found 10 frameshift mutations in the repeat, nine for CRCs and one for GC. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (10/113) and MSS (0/90). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the mutations exhibited regional ITH in three of the CRCs (18.8%). Our data indicate GLI1 harbored not only frameshift mutation but also its mutational ITH, which together could be a feature of GC and CRC with MSI-H.
C1 [Lee, Hwa Ju] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 477
EP 481
DI 10.1007/s12253-017-0272-9
PG 5
ER
PT J
AU Zhao, D
Zhang, Y
Song, L
AF Zhao, Danyi
Zhang, Yang
Song, Lei
TI MiR-16-1 Targeted Silences Far Upstream Element Binding Protein 1 to Advance the Chemosensitivity to Adriamycin in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; microRNA-16-1; Far upstream element binding protein 1; Chemosensitivity; Adriamycin
ID Gastric cancer; microRNA-16-1; Far upstream element binding protein 1; Chemosensitivity; Adriamycin
AB Chemotherapy can prevent metastasis and recurrence of gastric cancer (GC), and is a well supplement for operation. But, chemotherapy resistance has severely restricted the application of chemotherapy. This study aimed to investigate the regulatory roles and molecular mechanism of miR-16-1 to the chemosensitivity to adriamycin in GC. In this study, the expression of miR-16-1 and FUBP1 was downregulated and up-regulated respectively in adriamycinresistant GC tissues and cell lines, and represented a negative relationship between them. MiR-16-1 could silence FUBP1 directly and specifically, FUBP1 was a target gene of miR- 16-1. Silence of FUBP1 inhibited the half maximal inhibitory concentration (IC50) of SGC7901/AR cell line to adriamycin, chemosensitivity enhanced significantly. Moreover, FUBP1 silence in SGC7901/AR cell line also inhibited proliferation and invasion, and advanced cell apoptosis. To sum up, the expression of miR-16-1 was positively related with the chemosensitivity of GC to adriamycin, and miR-16-1 could targeted silence FUBP1 to advance the chemosensitivity to adriamycin in GC, which might be a novel potential therapeutic target for GC.
C1 [Zhao, Danyi] Dalian Medical University, The Second Hospital, Department of Oncology, No. 467 Zhongshan Road, Shahekou District, 116027 Dalian, China.
[Zhang, Yang] Dalian Medical University, The Second Hospital, Department of Oncology, No. 467 Zhongshan Road, Shahekou District, 116027 Dalian, China.
[Song, Lei] Dalian Medical University, The Second Hospital, Department of Oncology, No. 467 Zhongshan Road, Shahekou District, 116027 Dalian, China.
RP Song, L (reprint author), Dalian Medical University, The Second Hospital, Department of Oncology, 116027 Dalian, China.
EM 23326942@qq.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 483
EP 488
DI 10.1007/s12253-017-0263-x
PG 6
ER
PT J
AU da Silva Calixto, P
Lopes, SO
dos Santos Maia, M
Herrero, STS
Longui, AC
Farias Melo, GC
de Carvalho Filho, RI
Soares, FL
de Medeiros, CA
Delatorre, P
khayat, SA
Burbano, RR
Lima, ME
AF da Silva Calixto, Poliane
Lopes, Sergio Otavio
dos Santos Maia, Mayara
Herrero, Satomi Takeno Sylvia
Longui, Alberto Carlos
Farias Melo, Germoglio Cynthia
de Carvalho Filho, Rodrigues Ivan
Soares, Ferreira Leonardo
de Medeiros, Correia Arnaldo
Delatorre, Plinio
khayat, Salim Andre
Burbano, Rodriguez Rommel
Lima, Moura Eleonidas
TI Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal cell carcinoma; Mismatch repair; Single nucleotide polymorphism; DSASP; Genotyping; Molecular markers
ID Basal cell carcinoma; Mismatch repair; Single nucleotide polymorphism; DSASP; Genotyping; Molecular markers
AB Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraiba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffinembedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific – PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.
C1 [da Silva Calixto, Poliane] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
[Lopes, Sergio Otavio] Clinica Dermatologica Santa Catarina, Departamento de DermatologiaJoao Pessoa, PB, Brazil.
[dos Santos Maia, Mayara] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
[Herrero, Satomi Takeno Sylvia] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
[Longui, Alberto Carlos] Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo, Programa de Pos-Graduacao em Ciencias da SaudeSao Paulo, SP, Brazil.
[Farias Melo, Germoglio Cynthia] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
[de Carvalho Filho, Rodrigues Ivan] Laboratorio de Analises Medicas – UNILAB, Depatamento de PatologiaJoao Pessoa, PB, Brazil.
[Soares, Ferreira Leonardo] Universidade Estadual da Paraiba, Departamento de FarmaciaCampina Grande, PB, Brazil.
[de Medeiros, Correia Arnaldo] Universidade Federal da Paraiba, Departamento de MedicinaJoao Pessoa, PB, Brazil.
[Delatorre, Plinio] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
[khayat, Salim Andre] Universidade Federal do Para, Instituto de Ciencias BiologicasBelem, PA, Brazil.
[Burbano, Rodriguez Rommel] Universidade Federal do Para, Instituto de Ciencias BiologicasBelem, PA, Brazil.
[Lima, Moura Eleonidas] Universidade Federal da Paraiba, Departamento de Biologia MolecularJoao Pessoa, PB, Brazil.
RP Lima, ME (reprint author), Universidade Federal da Paraiba, Departamento de Biologia Molecular, Joao Pessoa, Brazil.
EM eleonidas@pq.cnpq.br
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 489
EP 496
DI 10.1007/s12253-017-0265-8
PG 8
ER
PT J
AU Stasikowska-Kanicka, O
Wagrowska-Danilewicz, M
Danilewicz, M
AF Stasikowska-Kanicka, Olga
Wagrowska-Danilewicz, Malgorzata
Danilewicz, Marian
TI Immunohistochemical Analysis of Foxp3+, CD4+, CD8+ Cell Infiltrates and PD-L1 in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Treg; FoxP3; PD-L1; Oral cancer
ID Treg; FoxP3; PD-L1; Oral cancer
AB The immunoexpression of the PD-L1 and the number of immune infiltrating cells have been shown to be a significant prognostic factors in various human cancers. Immunohistochemical method was used to examine the immunoexpression of PD-L1 and number of Foxp3+, CD4+ , CD8+ cells in 78 cases of oral squamous cell carcinomas (OSCCs): with better prognosis - OSCCBP (n = 37), and with poorer prognosis - OSCCPP (n = 41), and 18 cases of normal mucosa as a control. The immunoexpression of PD-L1 and the mean number of Foxp3+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. The mean number of CD4+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. CD8+ cells were significantly more numerous in OSCCBP group in comparison to OSCCPP and control group. In both OSCCPP and OSCCBP groups there were positive significant correlations between number of Foxp3+ and CD4+ cells. We found positive correlations between the immunoexpression of PD-L1 and numbers of Foxp3+ cells, and negative correlation between the immunoexpression of PD-L1 and numbers of CD8+ cells in both OSCCPP and OSCCBP groups. We found also significant positive correlation between immunoexpression of PD-L1 and the number of CD4+ cells in OSCCPP group. In conclusion, our findings support the hypothesis of involvement of Tregs and PD-L1 in OSCC development and progression.
C1 [Stasikowska-Kanicka, Olga] Medical University of Lodz, Department of Nephropathology, ul. Czechoslowacka 8/10, 92-216 Lodz, Poland.
[Wagrowska-Danilewicz, Malgorzata] Medical University of Lodz, Department of Nephropathology, ul. Czechoslowacka 8/10, 92-216 Lodz, Poland.
[Danilewicz, Marian] Medical University of Lodz, Department of PathologyLodz, Poland.
RP Stasikowska-Kanicka, O (reprint author), Medical University of Lodz, Department of Nephropathology, 92-216 Lodz, Poland.
EM olga.stasikowska@umed.lodz.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 497
EP 505
DI 10.1007/s12253-017-0270-y
PG 9
ER
PT J
AU Cheng, Y
Ping, J
Chen, J
AF Cheng, Yang
Ping, Jian
Chen, Jianjie
TI Identification of Potential Gene Network Associated with HCV-Related Hepatocellular Carcinoma Using Microarray Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatitis C virus; Hepatocelluar carcinoma; Kyoto encyclopedia of gene and genomes pathway; Weighted gene co-expression network analysis; Differentially expressed gene
ID Hepatitis C virus; Hepatocelluar carcinoma; Kyoto encyclopedia of gene and genomes pathway; Weighted gene co-expression network analysis; Differentially expressed gene
AB In order to identify potential specific gene networks of Hepatitis C virus (HCV) related hepatocellular carcinoma (HCC), weighted gene co-expression network analysis (WGCNA) was performed, which may provide an insight into the potential mechanism of the HCC development. HCV-related HCC and normal sample data were downloaded from GEO, T test of limma package was used to screen different expression genes (DEGs); KEGG pathway was used to analyze related biochemical pathways, and WGCNA was used to construct clustering trees and screen hub genes in the HCC-specific modules. A total of 1151 DEGs were authenticated between the HCC and normal liver tissue samples, including 433 upregulated and 718 downregulated genes. Among these genes, three specific modules of HCC were constructed, including Tan, Yellow and Cyan, but only Yellow module had a significant enrichment score in substance combination module with three hub genes: SLA2547, EFNA4 and MME. Although Tan and Cyan separately had four and three hub genes, but the bio-functions of them did not have significant enrichment scores (score < 2). SLA2547, EFNA4 and MME may play important roles in the substance combination of HCV-related HCC, so studying the function of this gene network may provide us a deeper understanding of HCV-related HCC.
C1 [Cheng, Yang] Hospital for Infectious Diseases of Pudong New Area, Department of Liver Disease, No.46 Nong 3018, East Huaxia Road, 201299 Shanghai, China.
[Ping, Jian] Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.
[Chen, Jianjie] Hospital for Infectious Diseases of Pudong New Area, Department of Liver Disease, No.46 Nong 3018, East Huaxia Road, 201299 Shanghai, China.
RP Chen, J (reprint author), Hospital for Infectious Diseases of Pudong New Area, Department of Liver Disease, 201299 Shanghai, China.
EM prchenjianjie@126.com
CR Jin B, Wang W, Du G, Huang GZ, Han LT, Tang ZY et al, 2015, Identifying hub genes and dysregulated pathways in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci 19:592–601
Luna J, Scheel TH, Danino T, Shaw K, Mele A, Fak J et al, 2015, Hepatitis C virus RNA functionally sequesters miR-122. Cell 160: 1099–1110
Castello G, Scala S, Palmieri G, Curley SA, Izzo F, 2010, HCV-related hepatocellular carcinoma: from chronic inflammation to cancer. Clin Immunol 134:237–250
Petrizzo A, Caruso FP, Tagliamonte M, Tornesello ML, Ceccarelli M, Costa V et al, 2016, Identification and validation of HCC-specific Gene transcriptional signature for tumor antigen discovery. Sci Rep 6:29258
Kakehashi A, Ishii N, Sugihara E, Min G, Saya H, Wanibuchi H, 2016, CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma. Cancer Sci 107:609– 618
Boj S, Vanes J, Huch M, Li VW, Jose A, Hatzis P et al, 2012, Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151:1595– 1607
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Lambert MP, Paliwal A, Vaissiere T, Chemin I, Zoulim F, Tommasino M et al, 2011, Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake. J Hepatol 54:705–715
Hodo Y, Honda M, Tanaka A, Nomura Y, Arai K, Yamashita Tet al, 2013, Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C. Clin Cancer Res 19:1827–1837
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 507
EP 514
DI 10.1007/s12253-017-0273-8
PG 8
ER
PT J
AU Ruiz-Sauri, A
Garcia-Bustos, V
Granero, E
Cuesta, S
Sales, AM
Marcos, V
LLombart-Bosch, A
AF Ruiz-Sauri, Amparo
Garcia-Bustos, Victor
Granero, Eduardo
Cuesta, Salome
Sales, A Maria
Marcos, Victor
LLombart-Bosch, Antonio
TI Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clear cell renal cell carcinoma; Papillary renal cell carcinoma; Chromophobe renal cell carcinoma; Microvascular density; Microvascular area; Morphometry; CD31; CD34; Renal vascular patterns
ID Clear cell renal cell carcinoma; Papillary renal cell carcinoma; Chromophobe renal cell carcinoma; Microvascular density; Microvascular area; Morphometry; CD31; CD34; Renal vascular patterns
AB To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade.We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.
C1 [Ruiz-Sauri, Amparo] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
[Garcia-Bustos, Victor] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
[Granero, Eduardo] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
[Cuesta, Salome] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
[Sales, A Maria] University of Valencia, Department of PathologyValencia, Spain.
[Marcos, Victor] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
[LLombart-Bosch, Antonio] University of Valencia, Department of Pathology, Avda. Blasco Ibanez n° 15, 46010 Valencia, Spain.
RP Ruiz-Sauri, A (reprint author), University of Valencia, Department of Pathology, 46010 Valencia, Spain.
EM Amparo.Ruiz-Sauri@uv.es
CR Zhang B, Ji H, Yan D, Liu S, Shi B, 2014, Lack of association of microvessel density with prognosis of renal cell carcinoma: evidence from meta-analysis. Tumor Biol 35(3):2769–2776
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 515
EP 524
DI 10.1007/s12253-017-0262-y
PG 10
ER
PT J
AU Rabassa, EM
Pereyra, A
Pereyra, L
Segal-Eiras, A
Abba, CM
Croce, VM
AF Rabassa, E Martin
Pereyra, Adrian
Pereyra, Liliana
Segal-Eiras, Amada
Abba, C Martin
Croce, V Maria
TI Lewis x Antigen is Associated to Head and Neck Squamous Cell Carcinoma Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Antigenic expression; Head and neck squamous cell carcinoma; Risk and prognostic factors; Survival
ID Antigenic expression; Head and neck squamous cell carcinoma; Risk and prognostic factors; Survival
AB Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC. Lewis x and sialyl Lewis x expression were detected by immunohistochemistry; patient’s data, progression free, and overall survival were documented. A statistical correlation study of antigenic expression and patients´ histopathological variables was performed. Cox regression models with internal validation procedures were employed to analyze survival data. By immunohistochemistry, Lewis x was detected in 34/79 (43%) tumor samples, while sialyl Lewis x only in 11/79 (14%). Lewis x expression showed a positive correlation with tumor differentiation and a better overall survival for Lewis x + patients was detected. Moreover, multivariate Cox’s regression analysis showed that Lewis x is an independent predictor of better overall survival. The in silico analysis supported the presence of deregulated fucosyl (FUT4) and sialyltransferase (ST3GAL4) in the Lewis synthetic pathway related to patient survival. These results suggest that Lewis x expression is associated with a better outcome in patients with HNSCC.
C1 [Rabassa, E Martin] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Pereyra, Adrian] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Pereyra, Liliana] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Segal-Eiras, Amada] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Abba, C Martin] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
[Croce, V Maria] Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA)La Plata, Argentina.
RP Croce, VM (reprint author), Facultad de Ciencias Medicas, UNLP, Centro de Investigaciones Inmunologicas Basicas y Aplicadas (CINIBA), La Plata, Argentina.
EM crocevir@hotmail.com
CR Ferlay J, Soerjomataram I, Ervik M, et al, 2013, Cancer incidence and mortality worldwide: IARC CancerBase no. 11. International Agency for Research on Cancer, Lyon. Accessed 15 June 2015
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 525
EP 531
DI 10.1007/s12253-017-0269-4
PG 7
ER
PT J
AU Filho, RSP
Junior, AS
Begnami, DM
Ferreira, dOF
Nakagawa, TW
Spencer, MSBR
Bezerra, ST
Boggiss, EP
Lopes, A
AF Filho, Roberto Stevanato Paulo
Junior, Aguiar Samuel
Begnami, Dirlei Maria
Ferreira, de Oliveira Fabio
Nakagawa, Toshihiko Wilson
Spencer, Matheus Sobreira Batista Ranyell
Bezerra, Santoro Tiago
Boggiss, Edward Philip
Lopes, Ademar
TI Estrogen Receptor β as a Prognostic Marker of Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Survival; Estrogen receptor; Familial adenomatous polyposis; Hormonal receptors; Colorectal carcinogenesis
ID Colorectal cancer; Survival; Estrogen receptor; Familial adenomatous polyposis; Hormonal receptors; Colorectal carcinogenesis
AB The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival.We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-β and the progesterone and androgen receptors (480 analyses). The ER-β expression levels differed between the groups: the group with FAP polyps had lower ER-β expression than that of the sporadic polyp group.With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-β expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-β expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-β exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-β expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.
C1 [Filho, Roberto Stevanato Paulo] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Junior, Aguiar Samuel] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Begnami, Dirlei Maria] A. C. Camargo Cancer Hospital, Department of PathologySao Paulo, SP, Brazil.
[Ferreira, de Oliveira Fabio] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Nakagawa, Toshihiko Wilson] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Spencer, Matheus Sobreira Batista Ranyell] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Bezerra, Santoro Tiago] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Boggiss, Edward Philip] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
[Lopes, Ademar] A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, R. Professor Antonio Prudente, 211 Liberdade, 01509-010 Sao Paulo, SP, Brazil.
RP Filho, RSP (reprint author), A.C. Camargo Cancer Center, Colorectal Tumor Nucleus of the Pelvic Surgery Department, 01509-010 Sao Paulo, Brazil.
EM paulo.stevanato@accamargo.org.br
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 533
EP 540
DI 10.1007/s12253-017-0268-5
PG 8
ER
PT J
AU Sienkiewicz, B
Urbaniak-Kujda, D
Dybko, J
Drys, A
Hurkacz, M
Wrobel, T
Wiela-Hojenska, A
AF Sienkiewicz, Beata
Urbaniak-Kujda, Donata
Dybko, Jaroslaw
Drys, Andrzej
Hurkacz, Magdalena
Wrobel, Tomasz
Wiela-Hojenska, Anna
TI Influence of CYP2C19 Genotypes on the Occurrence of Adverse Drug Reactions of Voriconazole among Hematological Patients after Allo-HSCT
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adverse drug reactions; Voriconazole; CYP2C19; Genotyping; Hematology
ID Adverse drug reactions; Voriconazole; CYP2C19; Genotyping; Hematology
AB The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients’ protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions. The observation and reporting of ADR took place from the −1 until the +20th day of VCZ therapy. For statistical analysis the χ2 test was used (p < 0.05). Among the examined patients 23 suffered from at least one side effect during VCZ therapy. Most frequent ADR were gastrointestinal disturbances (n = 15), nervous system (n = 11) and skin (n = 7) disorders. Patients with at least one loss of function allele (*2) were more likely to experience adverse drug reactions than those, with different genotypes. Due to the limited number of patients the result could not be proven with a statistical significance. Previous determination of CYP2C19 genotype may be a useful tool for prevention of adverse drug reactions during VCZ prophylaxis among patients after allo-HSCT.
C1 [Sienkiewicz, Beata] Wroclaw Medical University, Faculty of Pharmacy, 211a Borowska St, 50-556 Wroclaw, Poland.
[Urbaniak-Kujda, Donata] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 4 Wybrzeze Pasteura St, 50-367 Wroclaw, Poland.
[Dybko, Jaroslaw] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 4 Wybrzeze Pasteura St, 50-367 Wroclaw, Poland.
[Drys, Andrzej] Wroclaw Medical University, Department of Physical Chemistry, 211a Borowska St, 50-556 Wroclaw, Poland.
[Hurkacz, Magdalena] Wroclaw Medical University, Faculty of Pharmacy, 211a Borowska St, 50-556 Wroclaw, Poland.
[Wrobel, Tomasz] Wroclaw Medical University, Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, 4 Wybrzeze Pasteura St, 50-367 Wroclaw, Poland.
[Wiela-Hojenska, Anna] Wroclaw Medical University, Faculty of Pharmacy, 211a Borowska St, 50-556 Wroclaw, Poland.
RP Sienkiewicz, B (reprint author), Wroclaw Medical University, Faculty of Pharmacy, 50-556 Wroclaw, Poland.
EM beata.sienkiewicz@gmail.com
CR Fleming S, Yannakou CK, Haeusler GM, Clark J, Grigg A, Heath CH, Bajel A et al, 2014, Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014. Intern Med J 44:1283–1297
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Summary of Product Characteristics Methotrexat-EBEWE, 2013, http://leki.urpl.gov.pl/files/26_MethotrexatEbewe.pdf. Accessed 15 Nov 2016
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 541
EP 545
DI 10.1007/s12253-017-0264-9
PG 5
ER
PT J
AU Pyo, JS
Kim, HJ
AF Pyo, Jung-Soo
Kim, Heon Joo
TI Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; Micropapillary pattern; Clinicopathological characteristics; Meta-analysis
ID Lung adenocarcinoma; Micropapillary pattern; Clinicopathological characteristics; Meta-analysis
AB The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor si z e , lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075–0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403–0.645). MP pattern was found in 0.150 (95% CI 0.008–0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027–0.322), 0.620 (95% CI 0.444–0.769), and 0.118 (95% CI 0.027–0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216–2.387, and 2.082, 95% CI 1.541–2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.
C1 [Pyo, Jung-Soo] Eulji University, School of Medicine, Department of Pathology, 95 Dunsanseo-ro, Seo-gu, 35233 Daejeon, South Korea.
[Kim, Heon Joo] Eulji University, School of Medicine, Department of Pathology, 95 Dunsanseo-ro, Seo-gu, 35233 Daejeon, South Korea.
RP Kim, HJ (reprint author), Eulji University, School of Medicine, Department of Pathology, 35233 Daejeon, South Korea.
EM kjh2000@eulji.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 653
EP 662
DI 10.1007/s12253-017-0295-2
PG 10
ER
PT J
AU Li, X
Li, B
Li, B
Guo, T
Sun, Z
Li, X
Chen, L
Chen, W
Chen, P
Mao, Y
Zeng, Y
AF Li, Xiaohan
Li, Bo
Li, Boan
Guo, Tongsheng
Sun, Zhiqiang
Li, Xiaoxi
Chen, Lin
Chen, Weijiao
Chen, Peng
Mao, Yuanli
Zeng, Yanjun
TI ITIH4: Effective Serum Marker, Early Warning and Diagnosis, Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mass spectrum; Liver diseases; Liver cancer; Cirrhosis patients; Biomarker; AFP
ID Mass spectrum; Liver diseases; Liver cancer; Cirrhosis patients; Biomarker; AFP
AB Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serumsamples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.
C1 [Li, Xiaohan] Medical University of PLA, Graduate Student TeamBeijing, China.
[Li, Bo] Medical University of PLA, Graduate Student TeamBeijing, China.
[Li, Boan] Medical University of PLA, Graduate Student TeamBeijing, China.
[Guo, Tongsheng] Medical University of PLA, Graduate Student TeamBeijing, China.
[Sun, Zhiqiang] Medical University of PLA, Graduate Student TeamBeijing, China.
[Li, Xiaoxi] Medical University of PLA, Graduate Student TeamBeijing, China.
[Chen, Lin] Medical University of PLA, Graduate Student TeamBeijing, China.
[Chen, Weijiao] Medical University of PLA, Graduate Student TeamBeijing, China.
[Chen, Peng] Medical University of PLA, Graduate Student TeamBeijing, China.
[Mao, Yuanli] Medical University of PLA, Graduate Student TeamBeijing, China.
[Zeng, Yanjun] Beijing University of Technology, 100 Pingleyuan, Chaoyang DistrictBeijing, China.
RP Zeng, Y (reprint author), Beijing University of Technology, Beijing, China.
EM yjzeng@bjut.edu.cn
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Zhang Z, ZhangY,WangY, Xu L, XuW(2015, Alpha-fetoprotein- L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma. Onco Targets Ther 31(9):123–129
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Zhao Y,Wang M, Cui C, Zhang L, Liao F, Li H, 2015, Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma. Cancer Biomark. 15:677–683
Bao YX, Yang Y, Zhao HR, Mao R, Xiao L, Zhang YF, 2013, Clinical significance and diagnostic value of Golgi-protein 73 in patients with early-stage primary hepatocellular carcinoma. Zhonghua Zhong Liu Za Zhi. 35:505–508
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Taneja S, Ahmad I, Sen S, Kumar S, Arora R, Gupta VK, Aggarwal R et al, 2011, Plasma pep tidome profiling of acute hepatitis E patients by MALDI-TOF/TOF. Proteome Sci 9:5
Wang J, Wang X, Lin S, Chen C, Wang C, Ma Q, Jiang B et al, 2013, Identification of kininogen-1 as a serum biomarker for the early detection of advanced colorectal adenoma and colorectal cancer. PLoS One 8:e70519
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 663
EP 670
DI 10.1007/s12253-017-0285-4
PG 8
ER
PT J
AU Szabo, E
Kosa, Cs
Babarczi, E
Sulyok, M
Ujhelyi, E
Banhegyi, D
Valyi-Nagy, I
AF Szabo, Eszter
Kosa, Csaba
Babarczi, Edit
Sulyok, Mihaly
Ujhelyi, Eszter
Banhegyi, Denes
Valyi-Nagy, Istvan
TI Prevalence of Anal Human Papillomavirus Infection in Hungarian Men Who Have Sex with Men
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anal cancer screening; HIV-infected MSM; HPV; HPV genotype; MSM; Risk factor
ID Anal cancer screening; HIV-infected MSM; HPV; HPV genotype; MSM; Risk factor
AB Anal cancer is one of the leading causes of death in non-AIDS defining cancers. Most of these cancers are associated with high risk HPV infection. So far, the prevalence and the significance of anal HPV-infection have not been studied in the Hungarian MSM population. The main objective of our study was to determine the prevalence and associated risk factors of HPV-infection in the Hungarian MSM community, particularly in HIV-infected MSM. Out of 109 examinations 92 samples (80 HIV-infected and 12 HIV-negative MSM) were evaluated for both cytological abnormalities and HPV genotyping PCR. Using a questionnaire all enrolled individuals were interviewed about their sexual behavior, socioeconomic factors, drug use and other known or suspected risk factors. In the HIV-infected cohort 97.5% of the examined individuals were positive for any HPV type. In this group we detected high risk (HR) HPV in 88.8%, low risk (LR) HPV in 75.0% and probably high risk (PHR) HPV in 47.5% and multiple HPV infectionwas absolutely common (82.5%). In the HIV-negative MSM group the incidence of HPV-infection was 58.3%. The respective rate of HR-HPV, LR-HPV and PHR-HPV genotypes were 33.3%, 58.4%, and 16.7%. In the HIV-negative group both HPV infection frequency and the prevalence of the pertinent genotypes were much lower. The Hungarian MSM population is severely infected with HPV and HR-HPV. High-risk sexual behaviors are strong predictors for acquiring HR-HPV co-infections. Our results underline the necessity of anal cancer screening and the introduction of the vaccination program in the high-risk population.
C1 [Szabo, Eszter] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai Laboratorium, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Kosa, Csaba] St. Istvan and St. Laszlo Hospital, 3th Department of Infectology, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Babarczi, Edit] Municipal Hospital, Del-Pest, Department of Pathology, Nagyvarad square 1, 1097 Budapest, Hungary.
[Sulyok, Mihaly] Semmelweis University, School of PhD Studies, Ulloi str. 26, 1085 Budapest, Hungary.
[Ujhelyi, Eszter] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai Laboratorium, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Banhegyi, Denes] St. Istvan and St. Laszlo Hospital, 3th Department of Infectology, Albert Florian str. 5-7, 1097 Budapest, Hungary.
[Valyi-Nagy, Istvan] St. Istvan and St Laszlo Hospital, Hepatology Center, Nagyvarad square 1, 1097 Budapest, Hungary.
RP Szabo, E (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai Laboratorium, 1097 Budapest, Hungary.
EM eszter.szabo321@gmail.com
CR Joseph DA, Miller JW, Wu X, Chen VW, Morris CR, Goodman MT, Villalon-Gomez JM, Williams MA, Cress RD, 2008, Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer 113:2892–2900., DOI 10.1002/cncr.23744
Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, Eheman C, Saraiya M, Bandi P, Saslow D, Cronin KA, Watson M, Schiffman M, Jane Henley S, Schymura MJ, Anderson RN, Yankey D, Edwards BK, 2013, Annual report to the nation on the status of cancer, 1975-2009, featuring the burden and trends in human papillomavirus, HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 105:175–201., DOI 10. 1093/jnci/djs491
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Coutlee F, Rouleau D, Petignat P, Ghattas G, Kornegay JR, Schlag P, Boyle S, Hankins C, Vezina S, Cote P, Macleod J, Voyer H, Forest P, Walmsley S, Franco E, Conners J, Grimshaw R, Haase D, Johnston L, SchlechW, Yuzicappi-Fayant A, Landis S, Smaill F, Austin T, Hammerberg O, Ralph T, Falutz J, Ferenczy A, Klein M, Labrecque L, Lalonde R, Noel G, Perron C, Routy JP, Toma E, Touchie C, Victor G, Cote L, Senay H, Trottier S, Williams K, Piche A, Sandre R, Binder L, Keystone D, Phillips A, Rachlis A, Salit I, Wagner C, Braitstein P, Burdge D, Harris M, Money D, Montaner J, 2006, Enhanced detection and typing of human papillomavirus, HPV, DNA in anogenital samples with PGMYprimers and the linear array HPV genotyping test. J Clin Microbiol 44: 1998–2006., DOI 10.1128/JCM.00104-06
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Palefsky JM, Giuliano AR, Goldstone S, Moreira ED, Aranda C, Jessen H, Hillman R, Ferris D, Coutlee F, Stoler MH, Marshall JB, Radley D,Vuocolo S, HauptRM,GurisD, Garner EIO, 2011, HPV vaccine against anal HPV infection and anal intraepithelial Neoplasia. N Engl J Med 365:1576–1585., DOI 10.1056/ NEJMoa1010971
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Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang Y-H, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D, 2011, Efficacy of Quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med 364:401–411., DOI 10.1056/NEJMoa0909537
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 671
EP 677
DI 10.1007/s12253-017-0292-5
PG 7
ER
PT J
AU Dilmac, S
Erin, N
Necdet, D
Tanriover, G
AF Dilmac, Sayra
Erin, Nuray
Necdet, Demir
Tanriover, Gamze
TI Nephronectin is Decreased in Metastatic Breast Carcinoma and Related to Metastatic Organs
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nephronectin; Breast cancer; Metastasis; 4TLM; 4THM
ID Nephronectin; Breast cancer; Metastasis; 4TLM; 4THM
AB Breast cancer causes death mostly due to distant metastasis. During metastasis, cancer cells create new conditions in which normal tissue structure can be disturbed. Nephronectin, which is the primary ligand for α8β1 integrin, plays an important role in kidney development. There are conflicting findings regarding its role in cancer progression and metastasis, especially in breast carcinoma. The aim of this study was to determine changes in nephronectin expression in primary tumor tissues and metastatic visceral organs, using metastatic and non-metastatic cell lines in a mouse model of breast cancer. In our study, 4T1-Liver Metastatic and 4T1- Heart Metastatic cells, originally derived from 4T1-murine breast carcinoma, and non-metastatic 67NR carcinoma cells were used. Cancer cells were injected orthotopically into the mammary gland of 8–10 week-old Balb-c mice. Primary tumors, lung, liver tissues were collected on 12th and 25th days after the tumor injection. Immunohistochemistry was used to determine expression of nephronectin in tissues. We also investigated the expression levels of the protein by using western blot technique. We found that lung and liver tissue of control animals (not-injected with tumor cells) expressed nephronectin which was lost in animals bearing metastatic tumor for 25 days. In accordance, nephronectin staining of lung and liver was preserved in animals injected with nonmetastatic 67NR tumors. These results demonstrate that loss of nephronectin may play an important role in formation metastatic milieu for cancer cells. This is the first study demonstrating that tumor-induced loss of nephronectin expression in visceral organs in which metastatic growth takes place.
C1 [Dilmac, Sayra] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, Campus, 07070 Antalya, Turkey.
[Erin, Nuray] Akdeniz University School of Medicine, Department of Medical PharmacologyAntalya, Turkey.
[Necdet, Demir] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, Campus, 07070 Antalya, Turkey.
[Tanriover, Gamze] Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, Campus, 07070 Antalya, Turkey.
RP Tanriover, G (reprint author), Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, 07070 Antalya, Turkey.
EM gamzetanriover@akdeniz.edu.tr
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Erin N, Korcum AF, Tanriover G, Kale S, Demir N, Koksoy S, 2015, Activation of neuroimmune pathways increases therapeutic effects of radiotherapy on poorly differentiated breast carcinoma. Brain Behav Immun 48:174–185., DOI 10.1016/j.bbi.2015.02.024
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 679
EP 688
DI 10.1007/s12253-017-0289-0
PG 10
ER
PT J
AU Pereira, SS
Costa, MM
Guerreiro, GS
Monteiro, PM
Pignatelli, D
AF Pereira, S Sofia
Costa, M Madalena
Guerreiro, G Susana
Monteiro, P Mariana
Pignatelli, Duarte
TI Angiogenesis and Lymphangiogenesis in the Adrenocortical Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adrenocortical tumors; Adrenocortical carcinoma; Lymphangiogenesis; Angiogenesis
ID Adrenocortical tumors; Adrenocortical carcinoma; Lymphangiogenesis; Angiogenesis
AB Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are non-functioning and benign, while adrenocortical carcinomas (ACC) are rare, usually very aggressive and often metastasized when first diagnosed. Our aim was to assess whether blood and lymph vessel density within ACTs correlate with the malignancy character or tumor functionality. For that, the microvascular distribution was evaluated by immunohistochemistry staining with D2– 40 antibody, for lymph vessels and CD-31 antibody, for blood vessels, in ACCs (n = 15), adenomas with Cushing syndrome (n = 9) and non-functioning adenomas (n = 10). The percentage of stained area was quantified by computerized morphometric analysis. D2–40 expression was significantly lower in ACC as compared to adenomas with Cushing syndrome (p < 0.01) and correlated positively with the expression of the steroidogenic acute regulatory protein (StAR) (R2 = 0.553, p < 0.001). CD31 expression was found to be significantly higher in ACC as compared to adenomas with Cushing syndrome (p < 0.05). Our results show that angiogenesis is increased in ACC, suggesting that this phenomenon may have an important role in ACT biological behavior, while lymph vascular density seems to be more closely related to the tumor functional status than malignancy.
C1 [Pereira, S Sofia] Universidade do Porto, Instituto de Investigacao e Inovacao em Saude (I3S)Porto, Portugal.
[Costa, M Madalena] University of Porto, Clinical and Experimental Endocrinology, Department of AnatomyPorto, Portugal.
[Guerreiro, G Susana] Universidade do Porto, Instituto de Investigacao e Inovacao em Saude (I3S)Porto, Portugal.
[Monteiro, P Mariana] University of Porto, Clinical and Experimental Endocrinology, Department of AnatomyPorto, Portugal.
[Pignatelli, Duarte] Universidade do Porto, Instituto de Investigacao e Inovacao em Saude (I3S)Porto, Portugal.
RP Pignatelli, D (reprint author), Universidade do Porto, Instituto de Investigacao e Inovacao em Saude (I3S), Porto, Portugal.
EM dpignatelli@ipatimup.pt
CR Allolio B, Hahner S, Weismann D, Fassnacht M, 2004, Management of adrenocortical carcinoma. Clin Endocrinol 60(3): 273–287
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Zhu Y, Xu Y, Chen D, Zhang C, RuiW, Zhao J, Zhu Q,Wu Y, Shen Z, Wang W, Ning G, Wang X, 2014, Expression of STAT3 and IGF2 in adrenocortical carcinoma and its relationship with angiogenesis. Clin Transl Oncol 16(7):644–649., DOI 10.1007/s12094- 013-1130-1
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Kyle LH, Meyer RJ, Canary JJ, 1957, Mechanism of adrenal atrophy in Cushing’s syndrome due to adrenal tumor. N Engl J Med 257(2):57–61., DOI 10.1056/NEJM195707112570203
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 689
EP 693
DI 10.1007/s12253-017-0259-6
PG 5
ER
PT J
AU Ieni, A
Angelico, G
Giuffre, G
Tuccari, G
AF Ieni, Antonio
Angelico, Giuseppe
Giuffre, Giuseppe
Tuccari, Giovanni
TI Discordance Rate of HER2 Status in Primary Gastric Cancer and Synchronous Lymph Node Metastases: Its Impact on Therapeutic Decision and Clinical Management
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Ieni, Antonio] Azienda Ospedaliera Universitaria, Department of Human PathologyMessina, Italy.
[Angelico, Giuseppe] Universita degli Studi di Catania, Policlinico G. Rodolico, Dipartimento Anatomia, Patologia diagnostica, Medicina legale, Igiene e Sanita PubblicaCatania, Italy.
[Giuffre, Giuseppe] Azienda Ospedaliera Universitaria, Department of Human PathologyMessina, Italy.
[Tuccari, Giovanni] Azienda Ospedaliera Universitaria, Department of Human PathologyMessina, Italy.
RP Ieni, A (reprint author), Azienda Ospedaliera Universitaria, Department of Human Pathology, Messina, Italy.
EM aieni@unime.it
CR Amato M, Perrone G, Righi D et al, 2017, HER2 status in gastric cancer: comparison between primary and distant metastatic disease. Pathol Oncol Res 23:55–61
Ieni A, Barresi V, Rigoli L et al, 2015, HER2 status in premalignant, early, and advanced neoplastic lesions of the stomach. Dis Markers 2015:234851
Grillo F, Fassan M, Sarocchi F et al, 2016, HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol 22:5879–5887
Ahn S, Ahn S,Van VranckenMet al, 2015, Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens. Oncotarget 6:38372–38380
Gullo I, Grillo F, Molinaro L et al, 2015, Minimum biopsy set for HER2 evaluation in gastric and gastro-esophageal junction cancer. Endosc Int Open 3:E165–E170
Park SR, Park YS, Ryu MH et al, 2016, Extra-gain of HER2- positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: results of GASTric cancer HER2 reassessment study 1, GASTHER1). Eur J Cancer 53: 42–50
Pagni F, Zannella S, Ronchi S et al, 2013, HER2 status of gastric carcinoma and corresponding lymph node metastasis. Pathol Oncol Res 19:103–109
Kochi M, FujiiM, Masuda S, et al., 2013, Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes. Diagn Pathol 21;8:191
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Ieni A, Barresi V, Caltabiano R et al, 2014, Discordance rate of HER2 status in primary gastric carcinomas and synchronous lymph node metastases: a multicenter retrospective analysis. Int J Mol Sci 15:22331–22341
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 695
EP 696
DI 10.1007/s12253-017-0276-5
PG 2
ER
PT J
AU Kim, H
Ahn, D
Sohn, HJ
Kim, YH
Lee, JH
Lee, H
AF Kim, Heejin
Ahn, Dongbin
Sohn, Ho Jin
Kim, Yong-Hee
Lee, Jae-Ho
Lee, Hyunsu
TI TERT Promoter Mutation and Telomere Length in Salivary Gland Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kim, Heejin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Ahn, Dongbin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Sohn, Ho Jin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Kim, Yong-Hee] Kyungpook National University, School of Medicine, Department of MicrobiologyDaegu, South Korea.
[Lee, Jae-Ho] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeol-daero, Dalseo-gu, 1095 Daegu, South Korea.
[Lee, Hyunsu] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeol-daero, Dalseo-gu, 1095 Daegu, South Korea.
RP Lee, H (reprint author), Keimyung University, School of Medicine, Department of Anatomy, 1095 Daegu, South Korea.
EM neuroana@dsmc.or.kr
CR Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R, 2013, TERT promoter mutations in familial and sporadic melanoma. Science 339(6122):959–961., DOI 10.1126/science.1230062
Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA, 2013, Highly recurrent TERT promoter mutations in human melanoma. Science 339(6122):957–959., DOI 10.1126/science.1229259
Qu Y, Shi L,Wang D, Zhang B, Yang Q, Ji M, Shi B, Hou P, 2014, Low frequency of TERT promoter mutations in a large cohort of gallbladder and gastric cancers. Int J Cancer 134(12):2993–2994., DOI 10.1002/ijc.28633
Lee H, Jin J-D, La B-M, Park W-J, Choi I-J, Lee J-H, 2016, TERT promoter mutation, telomere length, and TERT expression in gastric cancer. Int J Clin Exp Pathol 9(2):1758–1763
Liu T,Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, Larsson C, Xu D, 2014, The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 33(42):4978–4984., DOI 10.1038/onc.2013.446
Borah S, Xi L, Zaug AJ, Powell NM, Dancik GM, Cohen SB, Costello JC, Theodorescu D, Cech TR, 2015, Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer. Science 347(6225):1006–1010., DOI 10.1126/science.1260200
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 697
EP 698
DI 10.1007/s12253-017-0275-6
PG 2
ER
PT J
AU Kim, H
Ahn, D
Sohn, HJ
Kim, YH
Lee, JH
Lee, H
AF Kim, Heejin
Ahn, Dongbin
Sohn, Ho Jin
Kim, Yong-Hee
Lee, Jae-Ho
Lee, Hyunsu
TI Erratum to: TERT Promoter Mutation and Telomere Length in Salivary Gland Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
C1 [Kim, Heejin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Ahn, Dongbin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Sohn, Ho Jin] Kyungpook National University, Department of Otolaryngology - Head and Neck SurgeryDaegu, South Korea.
[Kim, Yong-Hee] Kyungpook National University, School of Medicine, Department of MicrobiologyDaegu, South Korea.
[Lee, Jae-Ho] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeol-daero, Dalseo-gu, 1095 Daegu, South Korea.
[Lee, Hyunsu] Keimyung University, School of Medicine, Department of Anatomy, Dalgubeol-daero, Dalseo-gu, 1095 Daegu, South Korea.
RP Lee, H (reprint author), Keimyung University, School of Medicine, Department of Anatomy, 1095 Daegu, South Korea.
EM neuroana@dsmc.or.kr
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2018
VL 24
IS 3
BP 699
EP 699
DI 10.1007/s12253-017-0294-3
PG 1
ER
PT J
AU Gregorio, CA
Lacerda, M
Figueiredo, P
Simoes, S
Dias, S
Moreira, NJ
AF Gregorio, C Ana
Lacerda, Manuela
Figueiredo, Paulo
Simoes, Sergio
Dias, Sergio
Moreira, Nuno Joao
TI Therapeutic Implications of the Molecular and Immune Landscape of Triple-Negative Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast cancer; Triple-negative breast cancer; Intrinsic subtype; Gene expression profiling; Targeted therapies; Immune checkpoint inhibitors
ID Breast cancer; Triple-negative breast cancer; Intrinsic subtype; Gene expression profiling; Targeted therapies; Immune checkpoint inhibitors
AB Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient’s prognosis and increased the predictive power to therapeutic response and clinical outcome. Molecular heterogeneity is also prominent in the triple-negative breast cancer subtype, and is reflected by the distinct prognostic and patient’s sensitivity to treatment, being chemotherapy the only systemic treatment currently available. From a therapeutic perspective, gene expression profiling of triple-negative tumors has notably contributed to the exploration of new druggable targets and brought to light the need to align these patients to the various therapies according to their triple-negative subtype. Additionally, the higher amount of tumor infiltrating lymphocytes, and the prevalence of an increased expression of PD-1 receptor and its ligand, PD-L1, in triple-negative tumors, created a new treatment opportunity with immune checkpoint inhibitors. This manuscript addresses the current knowledge on the molecular and immune profiles of breast cancer, and its impact on the development of targeted therapies, with a particular emphasis on the triple-negative subtype.
C1 [Gregorio, C Ana] University of Coimbra, Center for Neuroscience and Cell Biology – CNC.IBILI, Rua Larga, 3004-504 Coimbra, Portugal.
[Lacerda, Manuela] University of Porto, Department of Pathology and Immunology of ICBASPorto, Portugal.
[Figueiredo, Paulo] IPOFG-EPE - Portuguese Institute of Oncology Francisco GentilCoimbra, Portugal.
[Simoes, Sergio] University of Coimbra, Polo das Ciencias da Saude, FFUC - Faculty of PharmacyCoimbra, Portugal.
[Dias, Sergio] University of Lisbon, Faculty of Medicine, IMM – Institute of Molecular MedicineLisbon, Portugal.
[Moreira, Nuno Joao] University of Coimbra, Center for Neuroscience and Cell Biology – CNC.IBILI, Rua Larga, 3004-504 Coimbra, Portugal.
RP Moreira, NJ (reprint author), University of Coimbra, Center for Neuroscience and Cell Biology – CNC.IBILI, 3004-504 Coimbra, Portugal.
EM jmoreira@ff.uc.pt
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 701
EP 716
DI 10.1007/s12253-017-0307-2
PG 16
ER
PT J
AU Chen, Y
Mo, J
Jia, X
He, Y
AF Chen, Ying
Mo, Jun
Jia, Xi
He, Yang
TI The B7 Family Member B7-H6: a New Bane of Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE B7-H6; NKp30; Tumor immunity
ID B7-H6; NKp30; Tumor immunity
AB B7-H6 is a ligand of NKp30, which is an activating receptor of natural killer (NK) cells. High expression of B7-H6 is found in certain types of tumor cells, such as lymphoma, leukemia and gastric carcinoma. The expression of B7-H6 can be induced by inflammatory stress in healthy cells. The expression of B7-H6 is significantly correlated with distant metastasis status and post-operative prognosis in cancer patients. The effectiveness of B7-H6modified antitumor immunotherapy strategies had been verified in tumor-bearingmice, which opened a newdoor to targeted therapy. In this review, we will focus on the recent development on the roles of B7-H6 in tumor immunity, as well as mechanisms involved in the regulation of B7-H6 expression.
C1 [Chen, Ying] The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, 215006 Suzhou, China.
[Mo, Jun] The First Affiliated Hospital of Soochow University, Department of Orthopedics, 215006 Suzhou, China.
[Jia, Xi] The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, 215006 Suzhou, China.
[He, Yang] The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, 215006 Suzhou, China.
RP He, Y (reprint author), The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, 215006 Suzhou, China.
EM heyang1963@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 717
EP 721
DI 10.1007/s12253-017-0357-5
PG 5
ER
PT J
AU Ghafoor, Q
Baijal, Sh
Taniere, P
O’Sullivan, B
Evans, M
Middleton, G
AF Ghafoor, Qamar
Baijal, Shobhit
Taniere, Phillipe
O’Sullivan, Brendan
Evans, Matthew
Middleton, Gary
TI Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors and Non-Small Cell Lung Cancer (NSCLC) – Advances in Molecular Diagnostic Techniques to Facilitate Targeted Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Non-small cell lung cancer; NSCLC; Epidermal growth factor receptor tyrosine kinase inhibitors; EGFR TKIs; Molecular diagnostic techniques
ID Non-small cell lung cancer; NSCLC; Epidermal growth factor receptor tyrosine kinase inhibitors; EGFR TKIs; Molecular diagnostic techniques
AB A subset of patients with non-small cell lung cancer (NSCLC) respond well to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), due to the presence of sensitising mutations in the gene encoding EGFR. Mutations associated with resistance to first generation EGFR-TKIs have also been identified, which lead to therapeutic failure and the requirement for new drugs. Three generations of EGFR-TKIs have been developed and either have been, or are being, evaluated as first and/or second line therapeutic agents. In this review, we consider the advances in molecular diagnostic techniques that are used, or are in development, to facilitate the targeted EGFR TKI therapy of patients with NSCLC. A literature search was conducted in May 2017 using PubMed, and spanning the period September 2005 (EU approval date of erlotinib) to May 2017. Search terms used were: EGFR TKI, NSCLC, clinical trial, erlotinib, gefitinib, afatinib, EGFR mutations, Exon 19 deletion, and Leu858Arg. The use of molecular data, in conjunction with other clinical and diagnostic information, will assist physicians to make the best therapeutic choice for each patient with advanced NSCLC. Personalized medicine and a rapidly developing therapy landscape will enable these patients to achieve optimal responses to EGFR TKIs.
C1 [Ghafoor, Qamar] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Oncology, B15 2TH Birmingham, UK.
[Baijal, Shobhit] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Oncology, B9 5SS Birmingham, UK.
[Taniere, Phillipe] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Cellular Pathology, B15 2TH Birmingham, UK.
[O’Sullivan, Brendan] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Cellular Pathology, B15 2TH Birmingham, UK.
[Evans, Matthew] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Cellular Pathology, B15 2TH Birmingham, UK.
[Middleton, Gary] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Oncology, B15 2TH Birmingham, UK.
RP Ghafoor, Q (reprint author), University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Oncology, B15 2TH Birmingham, UK.
EM Qamar.Ghafoor@uhb.nhs.uk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 723
EP 731
DI 10.1007/s12253-017-0377-1
PG 9
ER
PT J
AU Davidson, TK
Zhu, Z
Balabanov, D
Zhao, L
Wakefield, RM
Bai, Q
Fang, Y
AF Davidson, T Kristoffer
Zhu, Ziwen
Balabanov, Dean
Zhao, Lei
Wakefield, R Mark
Bai, Qian
Fang, Yujiang
TI Beyond Conventional Medicine - a Look at Blueberry, a Cancer-Fighting Superfruit
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Blueberry; Phytochemicals; Cancer; Apoptosis; Anthocyanidin
ID Blueberry; Phytochemicals; Cancer; Apoptosis; Anthocyanidin
AB Nearly 40% of men and women will be diagnosed with cancer during their lifetime. Thus, there is a rapidly growing need for novel therapies to combat this deadly disease. One such method is the consumption of blueberries. Long coveted for their powerful antioxidant properties, more recent studies have demonstrated that blueberries also exhibit inherent abilities to prevent carcinogenesis, inhibit the proliferation of neoplastic cells, and reduce the risks of recurrence in patients in remission. This review will focus on the specific activities of blueberry derivatives in cancer cells across many different forms of cancer. Ultimately, such research could be helpful in the development of new strategies to treat cancer.
C1 [Davidson, T Kristoffer] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Balabanov, Dean] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhao, Lei] The First Affiliated Hospital of Anhui Medical University, Department of Infectious DiseaseHefei, China.
[Wakefield, R Mark] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Bai, Qian] University of Missouri, School of Medicine, Department of Surgery, 65212 Columbia, MO, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
EM yujiang.fang@dmu.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 733
EP 738
DI 10.1007/s12253-017-0376-2
PG 6
ER
PT J
AU Ren, X
Zhang, H
Cong, H
Wang, X
Ni, H
Shen, X
Ju, Sh
AF Ren, Xiaojuan
Zhang, Hui
Cong, Hui
Wang, Xudong
Ni, Hongbing
Shen, Xianjuan
Ju, Shaoqing
TI Diagnostic Model of Serum miR-193a-5p, HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Epithelium ovarian cancer; miRNA; miR-193a-5p; HE4; CA125
ID Epithelium ovarian cancer; miRNA; miR-193a-5p; HE4; CA125
AB Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P < 0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P > 0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P > 0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P = 0.016, P = 0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.
C1 [Ren, Xiaojuan] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Zhang, Hui] Nantong Tumor Hospital, Laboratory Medicine Center, #48 Qingnian Road, 226001 Nantong, JS, China.
[Cong, Hui] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Wang, Xudong] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Ni, Hongbing] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Shen, Xianjuan] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
[Ju, Shaoqing] Affiliated Hospital of Nantong University, Department of Laboratory Medicine, #20 Xisi Road, 226001 Nantong, JS, China.
RP Shen, X (reprint author), Affiliated Hospital of Nantong University, Department of Laboratory Medicine, 226001 Nantong, China.
EM juanxia819@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 739
EP 744
DI 10.1007/s12253-018-0392-x
PG 6
ER
PT J
AU Laskar, J
Bhattacharjee, K
Sengupta, M
Choudhury, Y
AF Laskar, Jeny
Bhattacharjee, Kasturi
Sengupta, Mahuya
Choudhury, Yashmin
TI Anti-Diabetic Drugs: Cure or Risk Factors for Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Anti-cancer effect; Anti-diabetic drugs; Cancer risk
ID Anti-cancer effect; Anti-diabetic drugs; Cancer risk
AB Anti-diabetic drugs are an important group of therapeutics used worldwide. Different anti-diabetic drugs lower blood glucose level by differentmechanisms. In recent years, numerous investigations have been performed based on both comparative and cohort studies, in order to establish the relationship between anti-diabetic pharmacotherapy and cancer incidence as well as mortality due to cancer. Some anti-diabetic drugs have been found to exhibit anti-cancer activitywhile others might increase the risk for cancer. The underlying cause for this disparity is likely to be the varying mechanisms of action of these drugs in controlling blood glucose level. This review discusses the various carcinogenic and/or anti-cancer effects of commonly used anti-diabetic drugs. The information is vital in view of the fact that diabetes mellitus is a commonly occurring disease with a rising incidence rate.
C1 [Laskar, Jeny] Assam University, Department of Biotechnology, 788011 Silchar, India.
[Bhattacharjee, Kasturi] Assam University, Department of Biotechnology, 788011 Silchar, India.
[Sengupta, Mahuya] Assam University, Department of Biotechnology, 788011 Silchar, India.
[Choudhury, Yashmin] Assam University, Department of Biotechnology, 788011 Silchar, India.
RP Choudhury, Y (reprint author), Assam University, Department of Biotechnology, 788011 Silchar, India.
EM yashminchoudhury@gmail.com;yashminchoudhury@aus.ac.in
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 745
EP 755
DI 10.1007/s12253-018-0402-z
PG 11
ER
PT J
AU Puneet, SM
Kazmi, RH
Kumari, S
Tiwari, S
Khanna, KA
Narayan, G
AF Puneet, S M
Kazmi, Raza Hasan
Kumari, Soni
Tiwari, Satendra
Khanna, Kumar Ajay
Narayan, Gopeshwar
TI Epigenetic Mechanisms and Events in Gastric Cancer-Emerging Novel Biomarkers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE DNA methylation; Epigenetics; Gastric cancer; Long noncoding RNA; microRNAs; Promoter methylation
ID DNA methylation; Epigenetics; Gastric cancer; Long noncoding RNA; microRNAs; Promoter methylation
AB Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis. The DNA methylation is a chemical change in the DNA sequence that most commonly occurs at cytosine moiety of CpG dinucleotide and histone, primarily on N- terminal tail that ultimately effect the interaction of DNA with chromatin modifying protein. Hypermethylation of tumor suppressor genes and global hypomethylation of oncogenes are widely studied epigenetic modifications. There are large number of publish reports regarding epigenetic events involving gastric cancer. These changes are potentially useful in identifying markers for early diagnosis and management of this lethal malignancy. Also, role of specific miRNAs and long non coding RNAs in regulation of gene expression is gaining interest and is a matter of further investigation. In this review, we aimed to summarize major epigenetic events (DNA methylation) in gastric cancer along with alteration in miRNAs and long non coding RNAs which plays an important role in pathology of this poorly understood malignancy.
C1 [Puneet, S M] Banaras Hindu University, Institute of Medical Science, Department of Surgery, 221005 Varanasi, India.
[Kazmi, Raza Hasan] Banaras Hindu University, Department of Molecular and Human Genetics, Institute of Science, 221005 Varanasi, India.
[Kumari, Soni] Banaras Hindu University, Department of Molecular and Human Genetics, Institute of Science, 221005 Varanasi, India.
[Tiwari, Satendra] Banaras Hindu University, Institute of Medical Science, Department of Surgery, 221005 Varanasi, India.
[Khanna, Kumar Ajay] Banaras Hindu University, Institute of Medical Science, Department of Surgery, 221005 Varanasi, India.
[Narayan, Gopeshwar] Banaras Hindu University, Department of Molecular and Human Genetics, Institute of Science, 221005 Varanasi, India.
RP Puneet, SM (reprint author), Banaras Hindu University, Institute of Medical Science, Department of Surgery, 221005 Varanasi, India.
EM puneetimsbhu@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 757
EP 770
DI 10.1007/s12253-018-0410-z
PG 14
ER
PT J
AU Paskal, W
Paskal, MA
Debski, T
Gryziak, M
Jaworowski, J
AF Paskal, Wiktor
Paskal, M Adriana
Debski, Tomasz
Gryziak, Maciej
Jaworowski, Janusz
TI Aspects of Modern Biobank Activity – Comprehensive Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Biobank; Personalized medicine; Biorepository; Biospecimen; Tissue Banking
ID Biobank; Personalized medicine; Biorepository; Biospecimen; Tissue Banking
AB Biobanks play an increasing role in contemporary research projects. These units meet all requirements to regard them as a one of the most innovative and up-to-date in the field of biomedical research. They enable conducting wide-scale research by the professional collection of biological specimens and correlated clinical data. Pathology units may be perceived roots of biobanking. The review aims at describing the concept of biobanks, their model of function and scientific potential. It comprises the division of biobanks, sample preservation methods and IT solutions as well as guidelines and recommendations for management of a vast number of biological samples and clinical data. Therefore, appropriate standard operating procedures and protocols are outlined. Constant individualization of diagnostic process and treatment procedures creates the niche for translational units. Thus, the role of biobanks in personalized medicine was also specified. The exceptionality of biobanks poses some new ethical-legal issues which have various solutions, in each legal system, amongst the world. Finally, distribution and activity of European biobanks are mentioned.
C1 [Paskal, Wiktor] Medical University of Warsaw, The Department of Histology and Embryology, ul. Banacha 1B, 02-097 Warsaw, Poland.
[Paskal, M Adriana] Medical University of Warsaw, The Department of Histology and Embryology, ul. Banacha 1B, 02-097 Warsaw, Poland.
[Debski, Tomasz] Centre of Postgraduate Medical Education, Plastic Surgery DepartmentWarsaw, Poland.
[Gryziak, Maciej] Medical University of Warsaw, The Department of Applied PharmacyWarsaw, Poland.
[Jaworowski, Janusz] Medical University of Warsaw, The Department of Applied PharmacyWarsaw, Poland.
RP Paskal, W (reprint author), Medical University of Warsaw, The Department of Histology and Embryology, 02-097 Warsaw, Poland.
EM wiktor.paskal@wum.edu.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 771
EP 785
DI 10.1007/s12253-018-0418-4
PG 15
ER
PT J
AU Kastelan, S
Gverovic Antunica, A
Beketic Oreskovic, L
Salopek Rabatic, J
Kasun, B
Bakija, I
AF Kastelan, Snjezana
Gverovic Antunica, Antonela
Beketic Oreskovic, Lidija
Salopek Rabatic, Jasminka
Kasun, Boris
Bakija, Ivana
TI Conjunctival Melanoma - Epidemiological Trends and Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Conjunctival melanoma; Epidemiology; Clinical features; Diagnosis; Management; Prognosis
ID Conjunctival melanoma; Epidemiology; Clinical features; Diagnosis; Management; Prognosis
AB Conjunctival melanoma is a rare but sight and life threatening malignancy. It accounts for 2%–5% of all ocular tumours and 5%–7% of all ocular melanomas with an incidence of 0.2–0.8 per million in the Caucasian population with rare cases reported in the non-Caucasians. In recent decades the incidence of uveal melanoma has been relatively stable whilst conjunctival and cutaneous melanoma have shown increasing incidence which may be connected to the result of environmental exposure to ultraviolet light. The dissimilarity in incidence between light and dark pigmented individuals observed in conjunctival melanomas compared to uveal and cutaneous melanomas may be related to differences in their histological structures and genetic profile. Recent molecular biological studies support the fact that each type of melanoma undergoes its own molecular changes and has characteristic biological behaviour. Further studies are required for each type of melanoma in order to ascertain their individual etiology and pathogenesis and based on this knowledge develop relevant preventative and treatment procedures.
C1 [Kastelan, Snjezana] University Hospital Dubrava, Department of OphthalmologyZagreb, Croatia.
[Gverovic Antunica, Antonela] General Hospital Dubrovnik, Department of OphthalmologyDubrovnik, Croatia.
[Beketic Oreskovic, Lidija] University Hospital for Tumors, Department of OncologyZagreb, Croatia.
[Salopek Rabatic, Jasminka] University Hospital Dubrava, Department of OphthalmologyZagreb, Croatia.
[Kasun, Boris] Special Hospital for Medical Rehabilitation Stubicke TopliceStubicke Toplice, Croatia.
[Bakija, Ivana] Psychiatric Hospital Sveti IvanZagreb, Croatia.
RP Kastelan, S (reprint author), University Hospital Dubrava, Department of Ophthalmology, Zagreb, Croatia.
EM snjezanakastelan@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 787
EP 796
DI 10.1007/s12253-018-0419-3
PG 10
ER
PT J
AU Ishiwata, T
Matsuda, Y
Yoshimura, H
Sasaki, N
Ishiwata, Sh
Ishikawa, N
Takubo, K
Arai, T
Junko, A
AF Ishiwata, Toshiyuki
Matsuda, Yoko
Yoshimura, Hisashi
Sasaki, Norihiko
Ishiwata, Shunji
Ishikawa, Naoshi
Takubo, Kaiyo
Arai, Tomio
Junko, Aida
TI Pancreatic cancer stem cells: features and detection methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Pancreatic cancer; Cancer stem cell/CSC; Sphere; Side population; Cancer stem cell marker
ID Pancreatic cancer; Cancer stem cell/CSC; Sphere; Side population; Cancer stem cell marker
AB Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high incidence of distant metastasis and recurrence. Cancer stem cells (CSCs), which are pluripotent, self-renewable, and capable of forming tumors, contribute to PDAC initiation and metastasis and are responsible for resistance to chemotherapy and radiation. Three types of experimental methods are commonly used to identify CSCs: CSC-specific marker detection, a sphere-formation assay that reveals cell proliferation under non-adherent conditions, and detection of side-population (SP) cells that possess high intracellular-to-extracellular pump functions. Several CSC-specific markers have been reported in PDACs, including CD133, CD24, CD44, CXCR4, EpCAM, ABCG2, c-Met, ALDH-1, and nestin. There remains controversy regarding which markers are specific to PDAC CSCs and which are expressed alone or in combination in CSCs. Examining characteristics of isolated CSCs and discovering CSC-specific treatment options are important to improve the prognosis of PDAC cases. This review summarizes CSC-detection methods for PDAC, including CSC-marker detection, the sphere-formation assay, and detection of SP cells.
C1 [Ishiwata, Toshiyuki] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 35-2 Sakae-cho, Itabashi-ku, 173-0015 Tokyo, Japan.
[Matsuda, Yoko] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 173-0015 Tokyo, Japan.
[Yoshimura, Hisashi] Nippon Veterinary and Life Science University, School of Veterinary Nursing and Technology, Department of Applied Science, 180-0022 Tokyo, Japan.
[Sasaki, Norihiko] Tokyo Metropolitan Institute of Gerontology, Research Team for Geriatric Medicine (Vascular Medicine), 173-0015 Tokyo, Japan.
[Ishiwata, Shunji] Kindai University, Faculty of Pharmacy, Division of Medical Pharmaceutics & Therapeutics, 3-4-1 Kowakae, Higashi-Osaka, 577-8502 Osaka, Japan.
[Ishikawa, Naoshi] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 35-2 Sakae-cho, Itabashi-ku, 173-0015 Tokyo, Japan.
[Takubo, Kaiyo] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 35-2 Sakae-cho, Itabashi-ku, 173-0015 Tokyo, Japan.
[Arai, Tomio] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 173-0015 Tokyo, Japan.
[Junko, Aida] Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 35-2 Sakae-cho, Itabashi-ku, 173-0015 Tokyo, Japan.
RP Ishiwata, T (reprint author), Tokyo Metropolitan Institute of Gerontology, Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, 173-0015 Tokyo, Japan.
EM tishiwat@tmig.or.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 797
EP 805
DI 10.1007/s12253-018-0420-x
PG 9
ER
PT J
AU Guo, P
Chen, W
Li, H
Li, M
Li, L
AF Guo, Pingping
Chen, Wenqi
Li, Huiyu
Li, Meiying
Li, Lisha
TI The Histone Acetylation Modifications of Breast Cancer and their Therapeutic Implications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast cancer; Histone acetylation; Histone deacetylation; Therapy
ID Breast cancer; Histone acetylation; Histone deacetylation; Therapy
AB The histone acetylation modifications (HAMs) influence a large number of cellular functions. They are mediated through histone acetyltransferase (HAT) and histone deacetylase (HDAC). Nowadays, people have realized that HAMs are crucial for development and prognosis of breast cancer. Investigations about abnormal HAMs in breast cancer focus on initiating molecular mechanisms in breast cancer development, identification of new biomarkers to predict breast cancer aggressiveness and the therapeutic potential. As HAMs are reversible, breast cancer may be treated by restoring HAMs to normal levels. Indeed, some HDAC inhibitors have been approved by the US Food and Drug Administration to treat certain cancers. Furthermore, HAT inhibitors, HAT activators and HDAC activators may also be used as drugs to treat breast cancer.
C1 [Guo, Pingping] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
[Chen, Wenqi] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
[Li, Huiyu] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
[Li, Meiying] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
[Li, Lisha] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
RP Li, L (reprint author), Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, 130021 Changchun, China.
EM 43973966@qq.com
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Min A, Im SA, Kim DK, Song SH, Kim HJ, Lee KH, Kim TY, Han SW, Oh DY, Kim TY, O'Connor MJ, Bang YJ, 2015, Histone deacetylase inhibitor, suberoylanilide hydroxamic acid, SAHA), enhances anti-tumor effects of the poly, ADP-ribose, polymerase, PARP, inhibitor olaparib in triple-negative breast cancer cells. Breast Cancer Research 17. , DOI 10.1186/s13058-015- 0534-y
SalvadorMA,Wicinski J, Cabaud O, Toiron Y, Finetti P, Josselin E, Lelievre H, Kraus-Berthier L, Depil S, Bertucci F, Collette Y, Birnbaum D, Charafe-Jauffret E, Ginestier C, 2013, The Histone Deacetylase Inhibitor Abexinostat Induces Cancer Stem Cells Differentiation in Breast Cancer with Low Xist Expression. Clin Cancer Res 19(23):6520-6531. , DOI 10.1158/1078-0432. CCR-13-0877
Kubo M, Kanaya N, Petrossian K, Ye JJ, Warden C, Liu Z, Nishimura R, Osako T, Okido M, Shimada K, Takahashi M, Chu PG, Yuan YC, Chen SA, 2013, Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589, panobinostat). Breast Cancer Res Treat 137(1):93-107. , DOI 10.1007/s10549-012-2332-x
Dastjerdi MN, Salahshoor MR, Mardani M, Hashemibeni B, Roshankhah S, 2013, The effect of CTB on P53 protein acetylation and consequence apoptosis on MCF-7 and MRC-5 cell lines. Advanced biomedical research 2:24. , DOI 10.4103/ 2277-9175.108005
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 807
EP 813
DI 10.1007/s12253-018-0433-5
PG 7
ER
PT J
AU Kelly, EM
Mohan, MH
Baird, WA
Ryan, JE
Winter, CD
AF Kelly, E Michael
Mohan, M Helen
Baird, W Alan
Ryan, J Elizabeth
Winter, C Des
TI Orphan Nuclear Receptors in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Orphan nuclear receptors; Colorectal cancer; Carcinogenesis; Signaling pathways; Nuclear receptors
ID Orphan nuclear receptors; Colorectal cancer; Carcinogenesis; Signaling pathways; Nuclear receptors
AB Colorectal cancer is one of the most common cancers worldwide, with an overall increased incidence annually. Despite improvements in treatment and surveillance, almost 50% develop recurrent and/or distant disease. Unknown cellular processes are the fundamental cause for treatment failure and metastatic disease. The interplay of chronic inflammation and carcinogenesis is well established. Recent work has highlighted the role of nuclear receptors and co-regulators in the inflammation to carcinogenesis process. Orphan nuclear receptors have been shown to be involved in numerous cellular processes, including both at a transcriptional and a non-genomic level. There is a significant emphasis to identify ligands that will interact and modify these nuclear receptors, with the long-term aim of developing novel pharmaceutical therapies. The identification of orphan nuclear receptor ligands will also help increase our current understanding of their role in cellular signaling, by enabling manipulation of these receptors. This review aims to provide a brief overview of some key orphan nuclear receptors which may be involved in colorectal cancer.
C1 [Kelly, E Michael] University College Dublin, UCD Veterinary Sciences CentreDublin, Ireland.
[Mohan, M Helen] University College Dublin, UCD Veterinary Sciences CentreDublin, Ireland.
[Baird, W Alan] University College Dublin, UCD Veterinary Sciences CentreDublin, Ireland.
[Ryan, J Elizabeth] St Vincent’s University Hospital, Centre for Colorectal Disease, Elm ParkDublin, Ireland.
[Winter, C Des] St Vincent’s University Hospital, Centre for Colorectal Disease, Elm ParkDublin, Ireland.
RP Kelly, EM (reprint author), University College Dublin, UCD Veterinary Sciences Centre, Dublin, Ireland.
EM Kellym11@tcd.ie
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 815
EP 819
DI 10.1007/s12253-018-0440-6
PG 5
ER
PT J
AU Mandl, J
Banhegyi, G
AF Mandl, Jozsef
Banhegyi, Gabor
TI The ER – Glycogen Particle – Phagophore Triangle: A Hub Connecting Glycogenolysis and Glycophagy?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Glycogen particle; Glycogenolysis; Endoplasmic reticulum; Glycophagy; Lysosome; Phagophore
ID Glycogen particle; Glycogenolysis; Endoplasmic reticulum; Glycophagy; Lysosome; Phagophore
AB Glycogen particle is an intracellular organelle, which serves as a carbohydrate reserve in various cells. The function of glycogen is not entirely known in several cell types. Glycogen can be mobilized for different purposes, which can be related to cellular metabolic needs, intracellular redox state, metabolic state of the whole organism depending on regulatory aspects and also on cell functions. Essentially there are two different ways of glycogen degradation localized in different cellular organelles: glycogenolysis or lysosomal breakdown by acid alpha-glucosidase. While glycogenolysis occurs in glycogen particles connected to endoplasmic reticulum membrane, glycogen particles can be also combined with phagophores forming autophagosomes. A subdomain of the endoplasmic reticulum membrane - omegasomes - are the sites for phagophore formation. Thus, three organelles, the endoplasmic reticulum, the phagophore and the glycogen particle forms a triangle in which glycogen degradation occurs. The physiological significance, molecular logic and regulation of the two different catabolic paths are summarized and discussed with special aspect on the role of glycogen particles in intracellular organelle homeostasis and on molecular pathology of the cell. Pathological aspects and some diseases connected to the two different degradation pathways of glycogen particles are also detailed.
C1 [Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Banhegyi, Gabor] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
RP Mandl, J (reprint author), Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Budapest, Hungary.
EM mandl.jozsef@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 821
EP 826
DI 10.1007/s12253-018-0446-0
PG 6
ER
PT J
AU Choi, JE
Lee, HJ
Kim, SM
Song, YS
Yoo, JN
Lee, HS
AF Choi, Ji Eun
Lee, Hwa Ju
Kim, Sung Min
Song, Yong Sang
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral Heterogeneity of Somatic Mutations for NRIP1, DOK1, ULK1, ULK2, DLGAP3, PARD3 and PRKCI in Colon Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumor suppressor gene; Frameshift mutation; Colon cancer; Microsatellite instability
ID Tumor suppressor gene; Frameshift mutation; Colon cancer; Microsatellite instability
AB Both NRIP1 and DOK1 genes are considered candidate tumor suppressor genes (TSGs). Also, cell polarity-related genes PARD3, PRKCI and DLGAP3, and autophagy-related genes ULK1 and ULK2 genes are considered to play crucial roles in tumorigenesis. The aim of our study was to find whether these genes were mutated in colorectal cancer (CRC). In a genome database, we observed that each of these genes harbored mononucleotide repeats in the coding sequences, which could be mutated in cancers with high microsatellite instability (MSIH). For this, we studied 124 CRCs for the frameshift mutations of these genes and their intratumoral heterogeneity (ITH). NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 harbored 18 (22.8%), 2 (2.5%), 2 (2.5%), 2 (2.5%), 5 (6.3%), 2 (2.5%) and 2 (2.5%) of 79 CRCs with MSI-H, respectively. However, we found no such mutations in microsatellite stable (MSS) cancers in the nucleotide repeats. We also studied ITH for the frameshift mutations in 16 cases of CRCs and detected that the frameshift mutations of NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 showed regional ITH in 5 (31.3%), 2 (12.5%), 0 (0%), 0 (0%), 1 (6.3%), 1 (6.3%) and 3 (18.8%) cases, respectively. Our data exhibit that candidate cancer-related genes NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 harbor mutational ITH as well as the frameshift mutations in CRC with MSI-H. Also, the results suggest that frameshift mutations of these genes might play a role in tumorigenesis through their inactivation in CRC.
C1 [Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hwa Ju] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Song, Yong Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 827
EP 832
DI 10.1007/s12253-017-0297-0
PG 6
ER
PT J
AU Horvath, J
Szabo, A
Tar, I
Dezso, B
Kiss, Cs
Marton, I
Scholtz, B
AF Horvath, Jozsef
Szabo, Adrien
Tar, Ildiko
Dezso, Balazs
Kiss, Csongor
Marton, Ildiko
Scholtz, Beata
TI Oral Health May Affect the Performance of mRNA-Based Saliva Biomarkers for Oral Squamous Cell Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OSCC; Saliva mRNA; Biomarker; Saliva based diagnostics; qPCR
ID OSCC; Saliva mRNA; Biomarker; Saliva based diagnostics; qPCR
AB Oral squamous cell carcinoma (OSCC) has a dismal 50% five-year survival rate, emphasizing the need to develop reliable and sensitive tools for early diagnosis. In this study we evaluated the performance of 7 previously identified, potential mRNA biomarkers of OSCC in saliva samples of Hungarian patients. Expression of the putative OSCC biomarkers (DUSP1, OAZ1, H3F3A, IL1B, IL8, SAT and S100P), 2 biomarkers of inflammation (IL6 and TNFα) and 8 putative normalizing genes was quantified from each sample using real-time quantitative PCR. In contrast with previous studies, the expression pattern of the 7 mRNA biomarkers was similar between OSCC patients and age-matched control patients in the Hungarian patient population. On the other hand, 5 of the 7 mRNA biomarkers were present at significantly higher levels in saliva samples of OSCC patients when compared to young control patients. The best biomarker combination could distinguish only the OSCC vs. young control patients, but not the OSCC vs. age-matched control patients. In conclusion, the significant differences between our results and previous studies, and the clinical characteristics of the patients suggest that inflammatory processes in the oral cavity may affect the performance of the 7 putative salivary mRNA biomarkers. Lastly, since IL6 mRNA was quantifiable in the majority of OSCC cases, but only in a few control samples, salivary IL6 mRNA may be utilized as part of a biomarker combination to detect OSCC.
C1 [Horvath, Jozsef] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
[Szabo, Adrien] University of Debrecen, Faculty of Dentistry, Department of Oral and Maxillofacial SurgeryDebrecen, Hungary.
[Tar, Ildiko] University of Debrecen, Faculty of Dentistry, Department of PeriodontologyDebrecen, Hungary.
[Dezso, Balazs] University of Debrecen, Faculty of Dentistry, Department of Oral PathologyDebrecen, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Marton, Ildiko] University of Debrecen, Faculty of Dentistry, Department of Restorative DentistryDebrecen, Hungary.
[Scholtz, Beata] University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular BiologyDebrecen, Hungary.
RP Scholtz, B (reprint author), University of Debrecen, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Debrecen, Hungary.
EM scholtz@med.unideb.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 833
EP 842
DI 10.1007/s12253-017-0296-1
PG 10
ER
PT J
AU Zhu, L
Zhang, Sh
Xun, Y
Jiang, Y
Xia, B
Chen, X
Wang, L
Jiang, H
Shenglin, M
AF Zhu, Lucheng
Zhang, Shirong
Xun, Yanping
Jiang, Yanping
Xia, Bing
Chen, Xueqin
Wang, Limin
Jiang, Hong
Shenglin, Ma
TI Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE T790 M; ctDNA; ARMS; ddPCR; SuperARMS; TKI resistance
ID T790 M; ctDNA; ARMS; ddPCR; SuperARMS; TKI resistance
AB Plasma mutation detection has the advantages of non-invasiveness and accessibility. Here, we evaluated three methods, the amplification refractory mutation system (ARMS), second-generation ARMS (SuperARMS), and droplet digital PCR (ddPCR), to assess their concordance and feasibility for the detection of mutations in plasma samples. Non-small lung cancer patients with stage IIIB/IV that were resistant to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment were enrolled. Blood samples were collected within 14 days after TKI resistance. Each sample was simultaneously assessed by the three methods. In total, 169 patients were enrolled; 54.4% were female, 72.2% were diagnosed with stage IV disease; and 97.6%had adenocarcinoma. T790Mmutations were detected in 42 (24.8%) of the 169 samples using ARMS, one of which carried the T790 M alone, 22 that also encoded exon 19 deletions, and 19 with L858R mutations. For the SuperARMS assay, 59 (34.9%) samples exhibited the T790 M mutation, and 110 (65.1%) showed no detectable T790 M mutation. ddPCR showed that 61 (36.1%) samples contained the T790 M mutation, whereas 108 (63.9%) were not positive. T790Mabundance ranged from 0.04%to 38.2%. The median T790 M abundance was 0.15% for total samples and 2.98% for T790 M mutation samples. The overall concordance was 78.7% (133/169) among ARMS, SuperARMS, and ddPCR. Compared with patients with stage III disease, patients with stage IV disease exhibited a higher T790 M mutation detection rate (28.7% vs. 14.9% by ARMS; 37.7% vs. 27.7% by SuperARMS; and 41.8% vs. 21.3% by ddPCR). Liquid biopsy showed promise and has the advantages of noninvasiveness and accessibility. T790 M detection based on circulating tumor DNA showed high concordance. Compared with non-digital platforms, ddPCR showed higher sensitivity and provided both frequency and abundance information, which might be important for treatment decisions.
C1 [Zhu, Lucheng] Hangzhou Cancer Hospital, Department of OncologyHangzhou, China.
[Zhang, Shirong] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Xun, Yanping] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Jiang, Yanping] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Xia, Bing] Hangzhou Cancer Hospital, Department of OncologyHangzhou, China.
[Chen, Xueqin] Hangzhou Cancer Hospital, Department of OncologyHangzhou, China.
[Wang, Limin] Nanjing Medical University, Hangzhou First People’s Hospital, Department of RespiratoryNanjing, China.
[Jiang, Hong] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Thoracic SurgeryNanjing, China.
[Shenglin, Ma] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
RP Shenglin, M (reprint author), Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, Nanjing, China.
EM mashenglin@medmail.com.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 843
EP 851
DI 10.1007/s12253-017-0286-3
PG 9
ER
PT J
AU Feng, L
Ma, J
Ji, H
Liu, Y
Hu, W
AF Feng, Linsen
Ma, Jianhua
Ji, Haiming
Liu, Yichun
Hu, Weixing
TI MiR-184 Retarded the Proliferation, Invasiveness and Migration of Glioblastoma Cells by Repressing Stanniocalcin-2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; miR-184; STC2; Proliferation; Migration; Invasion
ID Glioblastoma; miR-184; STC2; Proliferation; Migration; Invasion
AB To investigate the repression of miR-184 on Stanniocalcin-2 (STC2) and how this axis affects the propagation, invasiveness and migration ability of glioblastoma cells. RT-PCR was employed to determine the miR-184 and STC2 mRNA expression both in tissues and cells. Western blot was employed to determine the protein expression levels. The cells were transfected via lipofection. MTT, colony formation, invasion and scratch healing assays were conducted to study the propagation, invasiveness and migratory ability of glioblastoma cells, respectively. The dual luciferase reporter gene assay was conducted to determine whether miR-184 could directly bind to STC2 mRNA 3’UTR. MiR-184 was under-expressed whereas STC2 was over-expressed in glioblastoma tissues and cell line. The up-regulation of miR-184 significantly suppressed the propagation, migratory ability and invasion of glioblastoma cells, whereas the overexpression of STC2 restored this effect. MiR-184 was confirmed to directly target STC2. MiR-184 could retard the propagation, invasiveness and migratory ability of glioblastoma cells by suppressing STC2.
C1 [Feng, Linsen] Taixing People’s Hospital, Department of Neurosurgery, 225400 Taizhou, Jiangsu, China.
[Ma, Jianhua] Taixing People’s Hospital, Department of Neurosurgery, 225400 Taizhou, Jiangsu, China.
[Ji, Haiming] Taixing People’s Hospital, Department of Neurosurgery, 225400 Taizhou, Jiangsu, China.
[Liu, Yichun] Taixing People’s Hospital, Department of Neurosurgery, 225400 Taizhou, Jiangsu, China.
[Hu, Weixing] The First Affiliated Hospital of Nanjing Medical University, Department of Neurosurgery, No. 300 Guangzhou Road, 210029 Nanjing, Jiangsu, China.
RP Hu, W (reprint author), The First Affiliated Hospital of Nanjing Medical University, Department of Neurosurgery, 210029 Nanjing, China.
EM xinglaijun@126.com
CR Kouhkan F, Mobarra N, Soufi-Zomorrod M et al, 2016, MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1. J Med Genet 53:24–33
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 853
EP 860
DI 10.1007/s12253-017-0298-z
PG 8
ER
PT J
AU Uehara, K
Ikehara, F
Shibuya, R
Nakazato, I
Oshiro, M
Kiyuna, M
Tanabe, Y
Toyoda, Z
Kurima, K
Kina, Sh
Hisaoka, M
Kinjo, T
AF Uehara, Karina
Ikehara, Fukino
Shibuya, Ryo
Nakazato, Iwao
Oshiro, Mariko
Kiyuna, Masaya
Tanabe, Yasuka
Toyoda, Zensei
Kurima, Kiyoto
Kina, Shinichiro
Hisaoka, Masanori
Kinjo, Takao
TI Molecular Signature of Tumors with Monoallelic 13q14 Deletion: a Case Series of Spindle Cell Lipoma and Genetically-Related Tumors Demonstrating a Link Between FOXO1 Status and p38 MAPK Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Monoallelic 13q14 deletion; RB 1; FOXO 1; Reactive oxygen species; p38 MAPK
ID Monoallelic 13q14 deletion; RB 1; FOXO 1; Reactive oxygen species; p38 MAPK
AB Spindle cell/pleomorphic lipomas (SCLs), cellul a r angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rare benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher β- catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis.
C1 [Uehara, Karina] University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 207 Uehara, Nishihara, 903-0215 Okinawa, Japan.
[Ikehara, Fukino] University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 207 Uehara, Nishihara, 903-0215 Okinawa, Japan.
[Shibuya, Ryo] University of Occupational and Environmental Health, School of Medicine, Department of Pathology and OncologyFukuoka, Japan.
[Nakazato, Iwao] Okinawa Prefectural Nanbu Medical Center and Children’s Medical Center, Department of PathologyOkinawa, Japan.
[Oshiro, Mariko] Meio University, Faculty of International Studies, Health Information Management Major, Management and Information Science DivisionOkinawa, Japan.
[Kiyuna, Masaya] Tomishiro Chuo Hospital, Department of PathologyOkinawa, Japan.
[Tanabe, Yasuka] University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 207 Uehara, Nishihara, 903-0215 Okinawa, Japan.
[Toyoda, Zensei] University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 207 Uehara, Nishihara, 903-0215 Okinawa, Japan.
[Kurima, Kiyoto] University of the Ryukyus, Graduate School of Medicine, Department of Regenerative MedicineOkinawa, Japan.
[Kina, Shinichiro] University of the Ryukyus, Graduate School of Medicine, Department of Oral and Maxillofacial Functional RehabilitationOkinawa, Japan.
[Hisaoka, Masanori] University of Occupational and Environmental Health, School of Medicine, Department of Pathology and OncologyFukuoka, Japan.
[Kinjo, Takao] University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 207 Uehara, Nishihara, 903-0215 Okinawa, Japan.
RP Kinjo, T (reprint author), University of the Ryukyus, School of Health Sciences, Department of Basic Laboratory Sciences, 903-0215 Okinawa, Japan.
EM kinjotko@med.u-ryukyu.ac.jp
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Huang H, Tindall DJ, 2007, Dynamic FoxO transcription factors. J Cell Sci 120:2479–2487
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Hoogeboom D, Essers MA, Polderman PE, Voets E, Smits LM, Burgering BM, 2008, Interaction of FOXO with betacatenin inhibits beta-catenin/T cell factor activity. J Biol Chem 283:9224–9230
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 861
EP 869
DI 10.1007/s12253-017-0303-6
PG 9
ER
PT J
AU Perez-Ruiz, E
Rueda, A
Perez, L
Rivas-Ruiz, F
Torres, E
de Luque, V
Alvarez, M
Sevilla, I
Redondo, M
Padilla-Ruiz, M
Alba, E
Alonso, L
AF Perez-Ruiz, Elisabeth
Rueda, Antonio
Perez, Lidia
Rivas-Ruiz, Francisco
Torres, Esperanza
de Luque, Vanesa
Alvarez, Martina
Sevilla, Isabel
Redondo, Maximino
Padilla-Ruiz, Maria
Alba, Emilio
Alonso, Lorenzo
TI Expression and Prognostic Value of Oestrogen Receptor Beta in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Prognostic factor; Estrogen receptor beta; Wild-type isoform ERβ1
ID Colorectal cancer; Prognostic factor; Estrogen receptor beta; Wild-type isoform ERβ1
AB Differences between men and women in the incidence and biological mechanisms of colorectal cancer (CRC) suggest that estrogens may play a role in the pathogenesis of this disease. The identification of the human estrogen receptor beta (ERβ) and its expression in the intestinal mucosa led to further studies that revealed that estrogens have a protective function against CRC mediated by the activation of ERβ. However, ERβ expression and its role in CRC is controversial. The purpose of this study was to determine the distribution and prognostic value of ERβ expression in the intestinal mucosa of patients diagnosed and surgically treated for CRC, and its association with other known prognostic factors. A total of 109 paraffin-embedded samples of the wild-type ERβ isoformwere analyzed by immunohistochemical nuclear staining in patients with colorectal adenocarcinoma. Clinical/pathological and survival data were collected. Immunohistochemical quantification was performed using the category scoring system, which has been validated for assessing estrogen receptor alfa. The wildtype ERβ isoform –also called ERβ1– was positive in 101 patients (92.7%) and negative in nine patients (7.3%). Univariate analysis revealed that the absence of expression of the ERβ1 gene was correlated with mucinous adenocarcinoma (p < 0.05). Also, a non-significant tendency was observed for ERβ expression to be down-regulated in advanced tumors.With a median follow-up of 47 months, the overall survival and progression-free survival were not found to be associated with ERβ1 expression (p = 0.2). Although thewild-type ERβ isoform was expressed in most study patients with colorectal cancer, it does not seem to have any prognostic value for the course of the disease. Further studies should be conducted to investigate whether the down-regulation of ERβ expression has any biological function in mucinous colorectal cancer.
C1 [Perez-Ruiz, Elisabeth] Hospital Virgen de la Victoria, Division of Medical OncologyMalaga, Spain.
[Rueda, Antonio] Hospital Costa del Sol, Division of Medical OncologyMarbella, Spain.
[Perez, Lidia] Hospital Virgen de la Victoria, Patology DeparmentMalaga, Spain.
[Rivas-Ruiz, Francisco] Red de Investigacion en Servicios de Salud (REDISSEC)Marbella, Spain.
[Torres, Esperanza] Hospital Virgen de la Victoria, Division of Medical OncologyMalaga, Spain.
[de Luque, Vanesa] Hospital Virgen de la Victoria, Patology DeparmentMalaga, Spain.
[Alvarez, Martina] Hospital Virgen de la Victoria, Patology DeparmentMalaga, Spain.
[Sevilla, Isabel] Hospital Virgen de la Victoria, Division of Medical OncologyMalaga, Spain.
[Redondo, Maximino] Red de Investigacion en Servicios de Salud (REDISSEC)Marbella, Spain.
[Padilla-Ruiz, Maria] Red de Investigacion en Servicios de Salud (REDISSEC)Marbella, Spain.
[Alba, Emilio] Hospital Virgen de la Victoria, Division of Medical OncologyMalaga, Spain.
[Alonso, Lorenzo] Hospital Virgen de la Victoria, Division of Medical OncologyMalaga, Spain.
RP Perez-Ruiz, E (reprint author), Hospital Virgen de la Victoria, Division of Medical Oncology, Malaga, Spain.
EM eliperu@gmail.com
CR Siegel R, Naishadham D, Jemal A, 2013, Cancer statistics. CA Cancer J Clin 63:11–30
Sanchez MJ, Payer T, de Angelis R, Larranaga R, Capocaccia R, Martinez C, CIBERESP working group, 2010, Cancer incidence and mortality in Spain: estimates and projections for the period 1981–2012. Ann Oncol 21:30–36
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Wong NA, Malcomson RD, Jodrell DI, Groome NP, Harrison DJ, 2005, Saunders PT.ERbeta isoform expression in colorectal carcinomas: an in vivo and in vitro study of clinicapathological and molecular correlates. J Pathol 207:53–60
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 871
EP 879
DI 10.1007/s12253-017-0301-8
PG 9
ER
PT J
AU Foley, MN
Coll, J
Lowery, A
Hynes, OS
Kerin, JM
Sheehan, M
Brodie, C
Sweeney, K
AF Foley, M Niamh
Coll, M. Jill
Lowery, J. Aoife
Hynes, Oliver Sean
Kerin, J Michael
Sheehan, Margaret
Brodie, Caroline
Sweeney, J. Karl
TI Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER−/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pathology; Immunohistochemistry; Receptors; estrogen; Receptors; progesterone; Breast neoplasms
ID Pathology; Immunohistochemistry; Receptors; estrogen; Receptors; progesterone; Breast neoplasms
AB Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER−/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER−/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER−/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER−/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER−/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER−/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR and 43.7% were ER−/PR- None of the cases were confirmed to be ER−/PR+. The ER−/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who represent with symptoms should be considered to ensure appropriate clinical management.
C1 [Foley, M Niamh] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Coll, M. Jill] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Lowery, J. Aoife] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Hynes, Oliver Sean] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Kerin, J Michael] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Sheehan, Margaret] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Brodie, Caroline] University College Hospital Galway, Department of SurgeryGalway, Ireland.
[Sweeney, J. Karl] University College Hospital Galway, Department of SurgeryGalway, Ireland.
RP Foley, MN (reprint author), University College Hospital Galway, Department of Surgery, Galway, Ireland.
EM foleynm@tcd.ie
CR Anderson WF, Chatterjee N, Ershler WB et al, 2002, Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database. Breast Cancer Res Treat 76:27–36
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Harvey JM, Clark GM, Osborne CK, Allred DC, 1999, Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer. J Clin Oncol 17(5):1474– 1481
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Hefti MM, Hu R, Knoblauch NW, Collins LC, Haibe-Kains B, Tamimi RM, Beck AH, 2013, Estrogen receptor negative/ progesterone receptor positive breast cancer is not a reproducible subtype. Breast Cancer Res 15(4):R68
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 881
EP 884
DI 10.1007/s12253-017-0304-5
PG 4
ER
PT J
AU Zhang, X
Hu, L
Du, M
Wei, X
Zhang, J
Hui, Y
Chen, Ch
Li, G
Hou, J
AF Zhang, Xuefeng
Hu, Linkun
Du, Mingzhan
Wei, Xuedong
Zhang, Jun
Hui, Yu
Chen, Cheng
Li, Gang
Hou, Jianquan
TI Eukaryotic Elongation Factor 2 (eEF2) is a Potential Biomarker of Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Eukaryotic elongation factor 2; Immunohistochemistry
ID Prostate cancer; Eukaryotic elongation factor 2; Immunohistochemistry
AB Eukaryotic elongation factor 2 (eEF2), a key regulator of protein synthesis, is involved in the progression of several types of cancer. This first study was to investigate the relationships between eEF2 protein and prostate cancer (PCa). Immunohistochemical staining was used to verify eEF2 protein in a set of 97 formalin-fixed, paraffin-embedded primary PCa tissues. Expression of eEF2 protein in positive cells was characterized by cytoplasmic staining. Correlations with clinicopathological factors were evaluated by Chi-square or Fisher’s exact probability tests. eEF2 protein was found in 74 out of 97 (76.29%) patients. eEF2-positive had higher PSA and Gleason score than negative in all patients. In addition, the positive expression of eEF2 protein was significantly associated with PSA and Gleason score (P = 0.007 and 0.002). However, no significant correlations occurred between expression of eEF2 protein and TNM stage (P = 0.292). In those eEF2 proteinpositive patients, we have found staining intensity of eEF2 protein was not only associated with PSA and Gleason score, but also associated with TNM stage (P = 0, 0.014 and 0.001, respectively). To conclude, our study indicates that expression of eEF2 protein is a potential biomarker for evaluating PCa.
C1 [Zhang, Xuefeng] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Hu, Linkun] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Du, Mingzhan] First Affiliated Hospital of Soochow University, Department of Pathology, 899 Pinghai Road, 215031 Suzhou, China.
[Wei, Xuedong] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Zhang, Jun] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Hui, Yu] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Chen, Cheng] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Li, Gang] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
[Hou, Jianquan] First Affiliated Hospital of Soochow University, Department of Urology, 899 Pinghai Road, 215031 Suzhou, China.
RP Hou, J (reprint author), First Affiliated Hospital of Soochow University, Department of Urology, 215031 Suzhou, China.
EM xf192@163.com
CR Siegel RL, Miller KD, Jemal A, 2016, Cancer statistics, 2016. CA Cancer J Clin 66:7–30
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Sundi D, Schaeffer EM(2016, Progress in prognosis and prediction for men with prostate cancer. Eur Urol 22:30761–30768
Grzmil M, Hemmings BA, 2012, Translation regulation as a therapeutic target in cancer. Cancer Res 72:3891–3900
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Nakamura J, Aoyagi S, Nanchi I, Nakatsuka S, Hirata E, Shibata S, Fukuda M, Yamamoto Y, Fukuda I, Tatsumi N, Ueda T, Fujiki F, Nomura M, Nishida S, Shirakata T, Hosen N, Tsuboi A, Oka Y, Nezu R, Mori M, Doki Y, Aozasa K, Sugiyama H, Oji Y, 2009, Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle. Int J Oncol 34:1181–1189
Oji Y, Tatsumi N, Fukuda M, Nakatsuka S, Aoyagi S, Hirata E, Nanchi I, Fujiki F, Nakajima H, Yamamoto Y, Shibata S, Nakamru M, Hasegawa K, Takagi S, Fukada I, Hoshikawa T, Murakami Y, 2014, The translation elongation factor eEF2 is a novel tumorassociated antigen overexpressed in various types of cancers. Int J Oncol 44:1461–1469
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Pinke DE, Kalloger SE, Francetic T, Huntsman DG, Lee JM, 2008, The prognostic significance of elongation factor eEF1A2 on ovarian cancer. Gynecol Oncol 108:561–568
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Nowroozi MR, Momeni SA, Ohadian Moghadam S, Ayati E, Mortazavi A, Arfae S, Jamshidian H, Taherimahmoudi M, Ayati M, 2016, Prostate-specific antigen density and Gleason score predict adverse pathologic features in patients with clinically localized prostate cancer. Nephrourol Mon 8:39984–39987
Kgatle MM, Kalla AA, Islam MM, Sathekge M, Moorad R, 2016, Prostate cancer: epigenetic alterations, risk factors, and therapy. Prostate Cancer 6:435–445
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 885
EP 890
DI 10.1007/s12253-017-0302-7
PG 6
ER
PT J
AU Kozak, D
Glowacka-Mrotek, I
Nowikiewicz, T
Siedlecki, Z
Hagner, W
Sowa, M
Zegarski, W
AF Kozak, Dominika
Glowacka-Mrotek, Iwona
Nowikiewicz, Tomasz
Siedlecki, Zygmunt
Hagner, Wojciech
Sowa, Magdalena
Zegarski, Wojciech
TI Analysis of Undesirable Sequelae of Sentinel Node Surgery in Breast Cancer Patients – a Prospective Cohort Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Sentinel lymph node; Undesirable sequelae
ID Breast cancer; Sentinel lymph node; Undesirable sequelae
AB Use of sentinel lymph node biopsy limits the frequency and severity of sequelae of surgical treatment. However, the procedure itself may not be completely free of complications. The goal of this work was to analyze prospectively the occurrence of undesirable sequelae in patients undergoing sentinel lymph node biopsy as an isolated intervention in the axillary fossa. This prospective observational study was conducted on a group of 104 women. Patients were examined on five occasions: one day before the procedure, one day after the procedure, one month, three months, and six months after the procedure. At every stage of the study they were assessed for tactile sensation, range of motion in the shoulder joint, upper limb circumference, sensation abnormalities, winged scapula sign, and pain severity according to Visual Analogue Scale (VAS). In the study group we observed statistically significant differences, such as limited mobility in the shoulder joint (p ≤ 0.01), gradual increase in limb circumference on the operated side (p < 0.01) and pain (p ≤ 0.01). Despite relatively low invasiveness of the procedure, sentinel lymph node biopsy is not entirely devoid of the risk of undesirable sequelae.
C1 [Kozak, Dominika] Medical College of the Nicolaus Copernicus University in Torun, Clinic and Chair of Oncological SurgeryBydgoszcz, Poland.
[Glowacka-Mrotek, Iwona] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of Rehabilitation, Maria Curie-Sklodowskiej Street 9, 85-094 Bydgoszcz, Poland.
[Nowikiewicz, Tomasz] Medical College of the Nicolaus Copernicus University in Torun, Clinic and Chair of Oncological SurgeryBydgoszcz, Poland.
[Siedlecki, Zygmunt] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of NeurosurgeryBydgoszcz, Poland.
[Hagner, Wojciech] Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of Rehabilitation, Maria Curie-Sklodowskiej Street 9, 85-094 Bydgoszcz, Poland.
[Sowa, Magdalena] Medical College of the Nicolaus Copernicus University in Torun, Clinic and Chair of Oncological SurgeryBydgoszcz, Poland.
[Zegarski, Wojciech] Medical College of the Nicolaus Copernicus University in Torun, Clinic and Chair of Oncological SurgeryBydgoszcz, Poland.
RP Glowacka-Mrotek, I (reprint author), Collegium Medicum of the Nicolaus Copernicus University in Torun, Department of Rehabilitation, 85-094 Bydgoszcz, Poland.
EM iwona.glowacka@cm.umk.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 891
EP 897
DI 10.1007/s12253-017-0306-3
PG 7
ER
PT J
AU Yang, L
Yang, Z
Li, D
Liu, Z
Zou, Q
Yuan, Y
Xu, H
AF Yang, Liangliang
Yang, Zhulin
Li, Daiqiang
Liu, Ziru
Zou, Qiong
Yuan, Yuan
Xu, Huilan
TI Overexpression of FZD1 and CAIX are Associated with Invasion, Metastasis, and Poor-Prognosis of the Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic ductal adenocarcinoma; Immunohistochemistry; FZD1; CAIX
ID Pancreatic ductal adenocarcinoma; Immunohistochemistry; FZD1; CAIX
AB Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers have not yet been identified. This study was to investigate the clinical significance of FZD1 and CAIX in PDACs. FZD1 and CAIX protein expression was measured using EnVision immunohistochemistry. Positive FZD1 or CAIX expression was significantly higher in PDAC than that in precursor lesions (p < 0.01). Positive FZD1 or CAIX expression was significantly lower in cases with well-differentiated adenocarcinoma, no-metastasis of the lymph node, no-invasion of regional tissues, and TNM I/II stage disease than in cases with poorlydifferentiated adenocarcinoma, metastasis and invasion, and TNM stage III+ IV stage disease (p < 0.05 or p < 0.01). The expression of FZD1 positively correlated with CAIX in PDAC (P = 0.000). Univariate Kaplan-Meier analysis showed that FZD1 and/or CAIX expression (p < 0.001) was significantly associated with shorter overall survival (p < 0.05).Cox multivariate analysis showed that differentiation, tumor mass, lymph node metastasis, invasion, TNM stage, FZD1 and CAIX levels negatively correlated with overall survival. Positive FZD1 and CAIX expressions are poor prognostic factors in PDAC patients. FZD1 and CAIX might be important biological markers for the carcinogenesis, metastasis, invasion, and prognosis of PDAC.
C1 [Yang, Liangliang] Central South University, Public Health College, 410078 Changsha, Hunan, China.
[Yang, Zhulin] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary DiseasesChangsha, Hunan, China.
[Li, Daiqiang] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
[Liu, Ziru] Central South University, Second Xiangya Hospital, Research Laboratory of Hepatobiliary DiseasesChangsha, Hunan, China.
[Zou, Qiong] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
[Yuan, Yuan] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
[Xu, Huilan] Central South University, Public Health College, 410078 Changsha, Hunan, China.
RP Xu, H (reprint author), Central South University, Public Health College, 410078 Changsha, China.
EM xhl6363@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 899
EP 906
DI 10.1007/s12253-017-0284-5
PG 8
ER
PT J
AU Tang, L
Wang, D
Gu, D
AF Tang, Liang
Wang, Dong
Gu, Dongyun
TI Knockdown of Sox2 Inhibits OS Cells Invasion and Migration via Modulating Wnt/β-Catenin Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Sox2; Wnt/β-catenin
ID Osteosarcoma; Sox2; Wnt/β-catenin
AB Osteosarcoma (OS) was a prevalent malignant bone tumor which threatens people’s health worldwide.Wnt/β catenin signaling pathway had been proved significant in various cancers, indicating its possible function in OS as well. Sox2, a crucial member among SOX family could regulate cells biologically. How Sox2 modulated Wnt/β catenin signaling pathway in OS remained to be discussed. The study aimed to investigate the effects of Sox2 on the invasion and migration of OS cells and the related molecular mechanisms. Twenty-four human OS and adjacent tissue samples were involved in this study. Human OS cell lines MG63 and HOS were selected for further investigation. The liposome carrier si-Sox2 which could interfere with the expression of Sox2 gene was built to transfect MG63 and HOS cells). QRT-PCR assay and western blot were utilized to analyze the expression ofm RNA and proteins of Sox2. Transwell assay and wound healing assay were conducted to test the invasion and migration level of cells. The expression of GSK3, β-catenin, cyclin D1 and c-myc proteins were detected by western blot assay after transfection with si-Sox2. Compared with normal tissues and cells, the expression of Sox2 in OS tissues and cells was significantly higher. The mRNA and protein levels of Sox2 significantly decreased after transfection with si-Sox2. The invasion and migration of OS cells were down-regulated significantly through the inhibition of Sox2 by inactivating Wnt/β-catenin signaling pathway related proteins. Knockdown of Sox2 could inhibit invasion and migration of OS cells via modulating Wnt/β-catenin signaling pathway.
C1 [Tang, Liang] Shanghai Jiao Tong University School of Medicine, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Key Laboratory of Orthopaedic Implants, 200011 Shanghai, China.
[Wang, Dong] Shanghai Jiao Tong University School of Medicine, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Key Laboratory of Orthopaedic Implants, 200011 Shanghai, China.
[Gu, Dongyun] Shanghai Jiao Tong University School of Medicine, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Key Laboratory of Orthopaedic Implants, 200011 Shanghai, China.
RP Gu, D (reprint author), Shanghai Jiao Tong University School of Medicine, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Key Laboratory of Orthopaedic Implants, 200011 Shanghai, China.
EM dongyungu@sjtu.edu.cn
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Yang C, Hou C, Zhang H, Wang D, Ma Y, Zhang Y, Xu X, Bi Z, Geng S, 2013, miR-126 functions as a tumor suppressor in osteosarcoma by targeting Sox2. Int J Mol Sci 15(1):423–437. https:// doi.org/10.3390/ijms15010423
Moradi A, Ghasemi F, Anvari K, Hassanian SM, Simab SA, Ebrahimi S, Hesari A, Forghanifard MM, Boroushaki MT, ShahidSales S, Avan A, 2017, The cross-regulation between SOX15 and Wnt signaling pathway. J Cell Physiol 232(12): 3221–3225. , DOI 10.1002/jcp.25802
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Ten Kate FJC, van Olphen SH, Bruno MJ, Wijnhoven BPL, van Lanschot JJB, Looijenga LHJ, Fitzgerald RC, Biermann K, 2017, Loss of SRY-box2, SOX2, expression and its impact on survival of patients with oesophageal adenocarcinoma. Br J Surg 104(10): 1327–1337. , DOI 10.1002/bjs.10553
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Liu H, Chen Y, Zhou F, Jie L, Pu L, Ju J, Li F, Dai Z,Wang X, Zhou S, 2014, Sox9 regulates hyperexpression of Wnt1 and Fzd1 in human osteosarcoma tissues and cells. Int J Clin Exp Pathol 7(8): 4795–4805
Bao Y, Chen B, Wu Q, Hu K, Xi X, Zhu W, Zhong X, Chen J, 2017, Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7. Clin Exp Med 17(1):51–58. , DOI 10.1007/ s10238-015-0398-6
Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C, 2005, Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 168(7):1065–1076. , DOI 10.1083/jcb.200409182
Zou Y, Huang Y, Yang J, Wu J, Luo C, 2017, miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity.Mol Med Rep 15(4):1631–1637. , DOI 10.3892/mmr.2017.6187
Ren C, Ren T, Yang K, Wang S, Bao X, Zhang F, Guo W, 2016, Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing's sarcoma through the PI3K/Akt pathway. J Exp Clin Cancer Res 35:44. , DOI 10.1186/s13046-016-0321-3
Martins-Neves SR, Corver WE, Paiva-Oliveira DI, van den Akker BE, Briaire-de-Bruijn IH, Bovee JV, Gomes CM, Cleton-Jansen AM, 2016, Osteosarcoma stem cells have active Wnt/beta-catenin and Overexpress SOX2 and KLF4. J Cell Physiol 231(4):876–886. , DOI 10.1002/jcp.25179
Li C, Shi X, Zhou G, Liu X, Wu S, Zhao J, 2013, The canonical Wnt-beta-catenin pathway in development and chemotherapy of osteosarcoma. Front Biosci 18:1384–1391
Krishnan V, Bryant HU, Macdougald OA, 2006, Regulation of bone mass by Wnt signaling. J Clin Invest 116(5):1202–1209. , DOI 10.1172/JCI28551
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 907
EP 913
DI 10.1007/s12253-018-0400-1
PG 7
ER
PT J
AU Crowley, PM
Prabhakaran, NV
Gilligan, MO
AF Crowley, P Maeve
Prabhakaran, N Vinitha
Gilligan, M Oonagh
TI Incidence of Contrast-Induced Nephropathy in Patients with Multiple Myeloma Undergoing Contrast-Enhanced Procedures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiple myeloma; Contrast induced nephropathy; Complications
ID Multiple myeloma; Contrast induced nephropathy; Complications
AB Multiple myeloma (MM) is a malignant disorder characterized by clonal proliferation of plasma cells. Renal impairment is a common complication. Contrast-induced nephropathy (CIN) is a form of acute renal failure that can occur in the setting of IV contrast administration. It is more commonly seen in patients with pre-existing renal impairment. Patients with MM commonly require contrast enhanced procedures. The literature regarding the safety of IV contrast in this cohort is lacking. A retrospective review was carried out in a university hospital to identify the incidence of CIN in patients with MM and to look for associated risk factors. 94 patients and 165 procedures were included in the analysis. 10% of procedures resulted in CIN. 59% (10/17) of creatinines had normalized within one month of the procedure. The only factor found to be significant for the development of CIN was the timing of the procedure (<18mths verses >18mths post diagnosis of MM; p = 0.045). CIN appears to occur at an increased rate in patients with MM. However this may be an over-estimation given the common occurrence of renal impairment in this cohort and the close temporal relationship which often exists between systemic illness and contrast-enhanced procedures.
C1 [Crowley, P Maeve] Cork University Hospital, Department of Haematology, WiltonCork, Ireland.
[Prabhakaran, N Vinitha] University College Cork, Department of MedicineCork, Ireland.
[Gilligan, M Oonagh] Cork University Hospital, Department of Haematology, WiltonCork, Ireland.
RP Crowley, PM (reprint author), Cork University Hospital, Department of Haematology, Cork, Ireland.
EM maeve.crowley@gmail.com
CR Kyle RA, Rajkumar SV, 2009, Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23(1):3–9
Society American Cancer, 2013, How many people get multiple myeloma? [updated 2/13/2013; cited 2013 12/3/2013]; Available from: http://www.cancer.org/cancer/multiplemyeloma/ overviewguide/multiple-myeloma-overview-key-statistics
Ireland National Cancer Rregistry, 2013, Cancer factsheet:multiple myeloma. [updated 16/12/2013; cited 2014 13/1/2014]; Available from: http://www.ncri.ie/
Blade J, Fernandez-Llama P, Bosch F et al, 1998, Renal failure in multiplemyeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med 158(17): 1889–1893
Heher EC, RennkeHG, Laubach JP et al, 2013, Kidney disease and multiple myeloma. Cli J Am Soc Nephrol: CJASN 8(11):2007– 2017
Berns AS, 1989, Nephrotoxicity of contrast media. Kidney Int 36(4):730–740
Stacul F, van der Molen AJ, Reimer P et al, 2011, Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21(12):2527–2541
Geenen RW, Kingma HJ, van der Molen AJ, 2013, Contrastinduced nephropathy: pharmacology, pathophysiology and prevention. Insights Imaging 4(6):811–820
Cicin I, Erdogan B, Gulsen E et al., 2014, Incidence of contrast induced nephropathy in hospitalised patients with cancer. Eur Radiol 24(1):184–190
McDonald JS, McDonald RJ, Comin J et al, 2013, Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology 267(1): 119–128
Holman RL, 1939, Complete anuria due to blockage of renal tubules by protein casts in a case of multiple myeloma. Arch Path 27: 748
Bartels ED, Brun GC, Gammeltoft A et al, 1954, Acute anuria following intravenous pyelography in a patient with myelomatosis. Acta Med Scand 150(4):297–302
Brodwall EK, Knutsen SB, Myhre JR, 1956, Acute renal failure following intravenous pyelography in cases of myelomatosis. Acta Med Scand 156(4):263–266
Killmann SA, Gjorup S, Thaysen JH, 1957, Fatal Acute Renal Failure Following Intravenous Pyelography in a Patient with Multiple Myeloma. Acta Med Scand 158(1):43–46
Perillie PE, Conn HO, 1958, Acute Renal Failure after Intravenous Pyelography in Plasma Cell Myeloma. Jama-J Am Med Assoc 167(18):2186–2189
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Brown M, Battle JD, 1964, Effect of Urography on Renal Function in Patients with Multiple Myeloma. Can Med Assoc J 91:786–790
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Defronzo RA, Humphrey RL,Wright JR et al, 1975, Acute Renal- Failure in Multiple-Myeloma. Medicine 54(3):209–223
Carvallo A, Rakowski TA, Argy WP et al, 1978, Acute Renal- Failure Following Drip Infusion Pyelography. Am J Med 65(1): 38–45
Cohen DJ, Sherman WH, Osserman EF et al, 1984, Acute-Renal- Failure in Patients withMultiple-Myeloma. Am J Med. 76(2):247– 256
Pahade JK, LeBedis CA, Raptopoulos VD et al, 2011, Incidence of contrast-induced nephropathy in patients with multiple myeloma undergoing contrast-enhanced CT. AJR Am J Roentgenol 196(5): 1094–1101
Mccarthy CS, Becker JA, 1992, Multiple-Myeloma and Contrast- Media. Radiology 183(2):519–521
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Lewington A, MacTier R, Hoefield R, Sutton A et al, 2013, Prevention of Contrast Induced Acute Kidney Injury, CI-AKI, in adult patients. Available from: http://www.rcr.ac.uk/docs/ radiology/pdf/2013_RA_BCIS_RCR.pdf
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 915
EP 919
DI 10.1007/s12253-017-0300-9
PG 5
ER
PT J
AU Lu, ChTh
Moretti, K
Beckmann, K
Cohen, P
O’Callaghan, M
AF Lu, Chengxuan Thomas
Moretti, Kim
Beckmann, Kerri
Cohen, Penelope
O’Callaghan, Michael
TI ISUP Group 4 – a Homogenous Group of Prostate Cancers?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Gleason score; Grade group 4; Biopsy; Prostate cancer specific mortality
ID Prostate cancer; Gleason score; Grade group 4; Biopsy; Prostate cancer specific mortality
AB The International Society of Urological Pathology (ISUP) and the World Health Organisation have adopted a five-tiered prognostic grade group for prostate cancer in 2014. Grade group 4 is comprised of Gleason patterns 4 + 4, 3 + 5 and 5 + 3. Recent articles have suggested heterogeneity in their prognostic outcomes.We aimed to determine whether there was a difference in mortality outcomes within the ISUP 4 grouping, as identified on needle biopsy. A total of 4080 men who were diagnosed with non-metastatic (N0 M0) prostate cancer on biopsy with Gleason scores of 7, 8 and 9 were included. Multi-variable Cox Regression and Fine and Grey competing risk analysis were used to determine the All-Cause Mortality (ACM) and the Prostate Cancer Specific Mortality (PCSM) as a function of Gleason Scores (Gleason 3 + 4, 4 + 3, 4 + 4, 3 + 5/5 + 3, 9). Gleason score 4 + 4 was utilized as the referent. The 60 months’ prostate cancer specific mortality with Gleason patterns 4 + 4 and 3 + 5/5 + 3 were 17% and 20%respectively (P < 0.01). Patients with 3 + 5/5 + 3 disease, had no statistically significant difference in the ACM (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [Cl] 0.68–1.4, p = 0.99) and PCSM risk (aHR 0.77, 95% Cl 0.47–1.2, p = 0.31) when compare with the referent group of patients. Patients with Gleason patterns 4 + 3 and 9 had statistically significant difference in their PCSM risk (aHR 0.70, 95% CI 0.54–0.91, P < 0.001 and aHR 1.5, 95% Cl 1.2–1.9, P < 0.001) when compared to the referent group. Our analysis suggest that ISUP group 4 is homogenous in terms of the allcause mortality and the prostate cancer specific morality risk as differentiated by the presence of Gleason 5 score.
C1 [Lu, Chengxuan Thomas] University of AdelaideAdelaide, Australia.
[Moretti, Kim] Queen Elisabeth Hospital, Repatriation HospitalWoodville, Australia.
[Beckmann, Kerri] South Australia Prostate Cancer Clinical Outcomes CollaborationAdelaide, Australia.
[Cohen, Penelope] Royal Adelaide Hospital, SA PathologyAdelaide, Australia.
[O’Callaghan, Michael] South Australia Prostate Cancer Clinical Outcomes CollaborationAdelaide, Australia.
RP Lu, ChTh (reprint author), University of Adelaide, Adelaide, Australia.
EM thomascxlu@gmail.com
CR Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, 2016, The 2014 International Society of Urological Pathology, ISUP, consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 40(2):244– 252. , DOI 10.1097/pas.0000000000000530
Huynh MA, Chen MH, Wu J, Braccioforte MH, Moran BJ, D'Amico AV, 2015, Gleason score 3 + 5 or 5 + 3 versus 4 + 4 prostate cancer: the risk of death. Eur Urol. , DOI 10.1016/ j.eururo.2015.08.054
Rusthoven CG, Waxweiler TV, DeWitt PE, Flaig TW, Raben D, Kavanagh BD, 2015, Gleason stratifications prognostic for survival in men receiving definitive external beam radiation therapy for localized prostate cancer. Urol Oncol 33(2):71.e11–71.e79. , DOI 10.1016/j.urolonc.2014.07.010
Harding-Jackson N, Kryvenko ON, Whittington EE, Eastwood DC, Tjionas GA, Jorda M, Iczkowski KA, 2016, Outcome of Gleason 3 + 5 = 8 prostate cancer diagnosed on needle biopsy: prognostic comparison with Gleason 4 + 4 = 8. J Urol 196(4): 1076–1081. , DOI 10.1016/j.juro.2016.05.105
van den Bergh RC, van der Kwast TH, de Jong J, Zargar H, Ryan AJ, Costello AJ, Murphy DG, van der Poel HG, 2016, Validation of the novel International Society of Urological Pathology 2014 fivetier Gleason grade grouping: biochemical recurrence rates for 3+5 disease may be overestimated. BJU Int 118(4):502–505. https://doi. org/10.1111/bju.13478
Mahal BA, Muralidhar V, Chen YW, Choueiri TK, Hoffman KE, JC H, Sweeney CJ, JB Y, Feng FY, Trinh QD, Nguyen PL, 2015, Gleason score 5 + 3 = 8 prostate cancer: much more like Gleason score 9? BJU Int. , DOI 10.1111/bju.13239
JacksonW, Hamstra DA, Johnson S, Zhou J, Foster B, Foster C, Li D, Song Y, Palapattu GS, Kunju LP, Mehra R, Feng FY, 2013, Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy. Cancer 119(18):3287–3294. , DOI 10.1002/cncr.28215
Sabolch A, Feng FY, Daignault-Newton S, Halverson S, Blas K, Phelps L, Olson KB, Sandler HM, Hamstra DA, 2011, Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation. Int J Radiat Oncol Biol Phys 81(4):e351–e360. https://doi. org/10.1016/j.ijrobp.2011.01.063
Esserman LJ, Thompson IM, Reid B, Nelson P, Ransohoff DF, Welch HG, Hwang S, Berry DA, Kinzler KW, Black WC, Bissell M, Parnes H, Srivastava S, 2014, Addressing overdiagnosis and overtreatment in cancer: a prescription for change. The Lancet Oncology 15(6):e234–e242. , DOI 10.1016/s1470- 2045(13)70598-9
Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi- Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA,Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA, 2016, A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428–435. https:// doi.org/10.1016/j.eururo.2015.06.046
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 921
EP 925
DI 10.1007/s12253-017-0331-2
PG 5
ER
PT J
AU Kiss, N
Krolopp,
Lorincz, K
Banvolgyi, A
Szipocs, R
Wikonkal, N
AF Kiss, Norbert
Krolopp, Adam
Lorincz, Kende
Banvolgyi, Andras
Szipocs, Robert
Wikonkal, Norbert
TI Stain-free Histopathology of Basal Cell Carcinoma by Dual Vibration Resonance Frequency CARS Microscopy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal cell carcinoma; Nonlinear microscopy; Coherent anti-stokes Raman scattering; Pseudo HE images; Cancer detection
ID Basal cell carcinoma; Nonlinear microscopy; Coherent anti-stokes Raman scattering; Pseudo HE images; Cancer detection
AB Basal cell carcinoma (BCC) is the most common malignancy in Caucasians. Nonlinear microscopy has been previously utilized for the imaging of BCC, but the captured images do not correlate with H&E staining. Recently, Freudiger et al. introduced a novel method to visualize tissue morphology analogous to H&E staining, using coherent anti-Stokes Raman scattering (CARS) technique. In our present work, we introduce a novel algorithm to post-process images obtained from dual vibration resonance frequency (DVRF) CARS measurements to acquire high-quality pseudo H&E images of BCC samples. We adapted our CARS setup to utilize the distinct vibrational properties of CH3 (mainly in proteins) and CH2 bonds (primarily in lipids). In a narrowband setup, the central wavelength of the pump laser is set to 791 nm and 796 nm to obtain optimal excitation. Due to the partial overlap of the excitation spectra and the 5–10 nm FWHM spectral bandwidth of our lasers, we set the wavelengths to 790 nm (proteins) and 800 nm (lipids). Nonresonant background from water molecules also reduces the chemical selectivity which can be significantly improved if we subtract the DVRF images from each other. As a result, we acquired two images: one for "lipids" and one for "proteins" when we properly set a multiplication factor to minimize the non-specific background. By merging these images, we obtained high contrast H&E "stained" images of BBC’s. Nonlinear microscope systems upgraded for real time DVRF CARS measurements, providing pseudo H&E images can be suitable for in vivo assessment of BCC in the future.
C1 [Kiss, Norbert] Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
[Krolopp, Adam] R&D Ultrafast Lasers Ltd, H-1539 Budapest, Hungary.
[Lorincz, Kende] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Banvolgyi, Andras] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Szipocs, Robert] Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
[Wikonkal, Norbert] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
RP Szipocs, R (reprint author), Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
EM r.szipocs@szipocs.com
CR Marzuka AG, Book SE, 2015, Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med 88(2):167–179
Clark CM, Furniss M, Mackay-Wiggan JM, 2014, Basal cell carcinoma: an evidence-based treatment update. Am J Clin Dermatol 15(3):197–216. , DOI 10.1007/s40257-014-0070-z
Seidenari S, Arginelli F, Bassoli S, Cautela J, Cesinaro AM, Guanti M, Guardoli D, Magnoni C, Manfredini M, Ponti G, Konig K, 2013, Diagnosis of BCC by multiphoton laser tomography. Skin Res Technol 19(1):e297–e304. , DOI 10.1111/j.1600-0846.2012.00643.x
Vogler N, Meyer T, Akimov D, Latka I, Krafft C, Bendsoe N, Svanberg K, Dietzek B, Popp J, 2010)Multimodal imaging to study the morphochemistry of basal cell carcinoma. J Biophotonics 3(10– 11):728–736. , DOI 10.1002/jbio.201000071
Heuke S, Vogler N,Meyer T, Akimov D, Kluschke F, Rowert-Huber HJ, Lademann J, Dietzek B, Popp J, 2013, Detection and discrimination of non-melanoma skin cancer by multimodal imaging. Healthcare, Basel, Switzerland, 1(1):64–83. , DOI 10. 3390/healthcare1010064
Freudiger CW, Pfannl R, Orringer DA, Saar BG, Ji M, Zeng Q, Ottoboni L, Wei Y, Waeber C, Sims JR, De Jager PL, Sagher O, Philbert MA, Xu X, Kesari S, Xie XS, Young GS, 2012, Multicolored stain-free histopathology with coherent Raman imaging. Lab Investig 92(10):1492–1502. , DOI 10.1038/ labinvest.2012.109
Haluszka D, Lorincz K, Kiss N, Szipocs R, Kuroli E, Gyongyosi N, Wikonkal NM, 2016, Diet-induced obesity skin changes monitored by in vivo SHG and ex vivo CARS microscopy. Biomed Opt Express 7(11):4480–4489. , DOI 10.1364/boe.7.004480
Duarte AS, Schnedermann C, Kukura P, 2016, Wide-field detected fourier transform CARS microscopy. Sci Rep 6:37516. https://doi. org/10.1038/srep37516
Krolopp A, Csakanyi A, Haluszka D, Csati D, Vass L, Kolonics A, Wikonkal N, Szipocs R, 2016, Handheld nonlinear microscope system comprising a 2 MHz repetition rate, mode-locked Yb-fiber laser for in vivo biomedical imaging. Biomed Opt Express 7(9):3531– 3542. , DOI 10.1364/boe.7.003531
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 927
EP 930
DI 10.1007/s12253-017-0356-6
PG 4
ER
PT J
AU Laus, CA
da Silva, DCGI
Cordeiro, BF
Lo Turco, GE
de Souza Viana, L
Carvalho, LA
AF Laus, Carolina Ana
da Silva, Dale Cotrim Guerreiro Ismael
Cordeiro, Bertuccez Fernanda
Lo Turco, Guimaraes Edson
de Souza Viana, Luciano
Carvalho, Lopes Andre
TI Is Lipidomic the Answer to the Search of a Biomarker for Organ Preservation Protocol in Head and Neck Squamous Cell Carcinoma?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck cancer; Induction chemotherapy; Lipidomics; Mass spectrometry; Biomarker; Response to treatment
ID Head and neck cancer; Induction chemotherapy; Lipidomics; Mass spectrometry; Biomarker; Response to treatment
AB In the last decade organ preservation protocols based on chemoradiotherapy (CRT) has been showing the possibility of preserving function without jeopardizing survival for locally advanced head and neck squamous cell carcinoma (HNSCC). Still, only a percentage of the patients will benefit from this approach and, to date, no biomarkers are known to correctly predict these patients. More recently, modern mass spectrometry method has been used to determine metabolic profiles, and lipidomics, in particular, emerged as a new field of study in oncology and other diseases. This study aimed to analyze the lipid profile on saliva from patients undergoing to a prospective, single center, open-label, nonrandomized phase II trial for organ preservation on HNSCC. The lipid analysis was performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Multivariate statistical analyses based on principal component analysis and orthogonal partial least square-discriminant analysis were applied to MALDI-TOFMS data to visualize differences between the lipid profiles and identify potential biomarkers. The results assisted on distinguishing complete responders from non-responders to the treatment protocol. In conclusion, we demonstrated that a group of lipids is differentially abundant in saliva from HNSCC patients submitted to an organ preservation protocol, being able to differentiate responders from non-responders. These results suggest the potential use of lipid biomarkers to identify patients who may benefit from this treatment. Also, we showed that saliva testing might be routinely used in clinical practice, for being a non-invasive alternative to blood testing, besides inexpensive and easy to obtain.
C1 [Laus, Carolina Ana] Barretos Cancer Hospital, Molecular Oncology Research Center, 1331, Antenor Duarte Villela St,, 14784-400 Barretos, SP, Brazil.
[da Silva, Dale Cotrim Guerreiro Ismael] Universidade Federal de Sao Paulo, Urology DisciplineSao Paulo, SP, Brazil.
[Cordeiro, Bertuccez Fernanda] Universidade Federal de Sao Paulo, Urology DisciplineSao Paulo, SP, Brazil.
[Lo Turco, Guimaraes Edson] Universidade Federal de Sao Paulo, Urology DisciplineSao Paulo, SP, Brazil.
[de Souza Viana, Luciano] Barretos Cancer Hospital, Pio XII, Clinical Oncology DepartmentBarretos, SP, Brazil.
[Carvalho, Lopes Andre] Barretos Cancer Hospital, Molecular Oncology Research Center, 1331, Antenor Duarte Villela St,, 14784-400 Barretos, SP, Brazil.
RP Laus, CA (reprint author), Barretos Cancer Hospital, Molecular Oncology Research Center, 14784-400 Barretos, Brazil.
EM anacarolinalaus@gmail.com
CR Argiris A, Karamouzis MV, Raben D, Ferris RL, 2008, Head and neck cancer. Lancet 371(9625):1695–1709
Bligh EG, Dyer WJ, 1959, A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917
Denaro N, Russi EG, Adamo V, Merlano MC, 2014, State-of-theart and emerging treatment options in the management of head and neck cancer: news from 2013. Oncology 86(4):212–229
Haddad RI, Shin DM, 2008, Recent advances in head and neck cancer. N Engl J Med 359(11):1143–1154
Hannun YA, Obeid LM, 2008, Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9(2):139– 150
Hilvo M, Gade S, Hyotylainen T, Nekljudova V, Seppanen-Laakso T, Sysi-Aho M et al, 2014, Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients. Int J Cancer 134(7):1725–1733
Holsinger FC, Lin HY, Bassot V, Laccourreye O, 2009, Platinbased exclusive chemotherapy for selected patients with squamous cell carcinoma of the larynx and pharynx. Cancer 115(17):3909– 3918
Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T, 1996, Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 88(13):890–899
Li X, Yuan YJ, 2011, Lipidomic analysis of apoptotic hela cells induced by Paclitaxel. Omics: J Integr Biol 15(10):655–664
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de Souza Viana L, de Aguiar Silva FC, Andrade Dos Anjos Jacome A, Calheiros CampeloMaia D, Duarte deMattos M, Arthur Jacinto A et al, 2016, Efficacy and safety of a cisplatin and paclitaxel induction regimen followed by chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma. Head Neck 38(1):E970–E980
Stegemann C, Drozdov I, Shalhoub J, Humphries J, Ladroue C, Didangelos A et al, 2011, Comparative lipidomics profiling of human atherosclerotic plaques. Circ Cardiovasc Genet 4(3):232–242
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, 2015, Global cancer statistics, 2012. CA Cancer J Clin 65(2):87– 108
Wang Q, Gao P, Wang X, Duan Y, 2014, The early diagnosis and monitoring of squamous cell carcinoma via saliva metabolomics. Sci Rep 4:6802
Wood PL, 2012, Lipidomics of Alzheimer's disease: current status. Alzheimers Res Ther 4(1):5
Zhao C, Mao J, Ai J, Shenwu M, Shi T, Zhang D et al, 2013, Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus. BMC Med Genet 6(1):S12
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 931
EP 935
DI 10.1007/s12253-017-0336-x
PG 5
ER
PT J
AU Kostovska, MI
Jakimovska, M
Popovska-Jankovic, K
Kubelka-Sabit, K
Karagjozov, M
Plaseska-Karanfilska, D
AF Kostovska, Maleva Ivana
Jakimovska, Milena
Popovska-Jankovic, Katerina
Kubelka-Sabit, Katerina
Karagjozov, Mitko
Plaseska-Karanfilska, Dijana
TI TIMP3 Promoter Methylation Represents an Epigenetic Marker of BRCA1ness Breast Cancer Tumours
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TIMP3; BRCA 1ness; MS-MLPA; Breast cancer
ID TIMP3; BRCA 1ness; MS-MLPA; Breast cancer
AB Tumours presenting BRCAness profile behave more aggressively and are more invasive as a consequence of their complex genetic and epigenetic alterations, caused by impaired fidelity of the DNA repair processes. Methylation of promoter CpG islands represents an alternative mechanism to inactivate DNA repair and tumour suppressor genes. In our study, we analyzed the frequency of methylation changes of 24 tumour suppressor genes and explored their association with BRCAness profile. BRCA1ness profile and aberrant methylation were studied in 233 fresh frozen breast tumour tissues by Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific (MS)-MLPA methods, respectively. Our analyses revealed that 12.4% of the breast cancer (BC) patients had tumours with a BRCA1ness profile. TIMP3 showed significantly higher (p = 5.8х10−5) methylation frequency in tumours with BRCA1ness, while methylation of APC, GSTP1 and RASSF1 promoters was negatively associated with BRCA1ness (р = 0.0017, р = 0.007 and р = 0.046, respectively). TIMP3 methylation was also associated with triple negative (TN) BC. Furthermore, TN tumours showing BRCA1ness showed stronger association with TIMP3 methylation (p = 0.0008) in comparison to TN tumours without BRCA1ness (p = 0.009). In conclusion, we confirmed that TIMP3 methylation is a marker for TN tumours and furthermore we showed for the first time that TIMP3 promoter methylation is an epigenetic marker of BRCA1ness tumours.
C1 [Kostovska, Maleva Ivana] Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Krste Misirkov 2Skopje, Macedonia.
[Jakimovska, Milena] Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Krste Misirkov 2Skopje, Macedonia.
[Popovska-Jankovic, Katerina] Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Krste Misirkov 2Skopje, Macedonia.
[Kubelka-Sabit, Katerina] Clinical Hospital Acibadem SistinaSkopje, Macedonia.
[Karagjozov, Mitko] Clinical Hospital Acibadem SistinaSkopje, Macedonia.
[Plaseska-Karanfilska, Dijana] Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Krste Misirkov 2Skopje, Macedonia.
RP Plaseska-Karanfilska, D (reprint author), Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Skopje, Macedonia.
EM dijana@manu.edu.mk
CR Lord CJ, Ashworth A, 2016, BRCAness revisited. Nat Rev Cancer 16(2):110–120
Turner N, Tutt A, Ashworth A, 2004, Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer 4(10):814–819
Jones PA, Baylin SB, 2007, The epigenomics of cancer. Cell 128(4):683–692
Lips EH, Laddach N, Savola SP, Vollebergh MA, Oonk AM, Imholz AL, Wessels LF, Wesseling J, Nederlof PM, Rodenhuis S, 2011, Quantitative copy number analysis by multiplex ligationdependent probe amplification, MLPA, of BRCA1-associated breast cancer regions identifies BRCAness. Breast Cancer Res 13(5):R107
Coffa J, van de Wiel MA, Diosdado B, Carvalho B, Schouten J, Meijer GA, 2008, MLPAnalyzer: data analysis tool for reliable automated normalization of MLPA fragment data. Cell Oncol 30(4):323–335
Nygren AO, Ameziane N, Duarte HM, Vijzelaar RN, Waisfisz Q, Hess CJ, Schouten JP, Errami A, 2005, Methylation-specific MLPA, MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res 33(14):e128
Cruz-Munoz W, Khokha R, 2008, The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 45(3):291–338
Lui EL, Loo WT, Zhu L, Cheung MN, Chow LW, 2005, DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma. Biomed Pharmacother 59(2):S363–S365
Bachman KE, Herman JG, Corn PG, Merlo A, Costello JF, Cavenee WK, Baylin SB, Graff JR, 1999, Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res 59(4):798–802
Mylona E, Magkou C, Giannopoulou I, Agrogiannis G, Markaki S, Keramopoulos A, Nakopoulou L, 2006, Expression of tissue inhibitor of matrix metalloproteinases, TIMP)-3 protein in invasive breast carcinoma: relation to tumor phenotype and clinical outcome. Breast Cancer Res 8(5):R57
Widschwendter M, Siegmund KD, Muller HM, Fiegl H, Marth C, Muller-Holzner E, Jones PA, Laird PW(2004)Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res 64(11):3807–3813
Murria R, Palanca S, de Juan I, Alenda C, Egoavil C, Segui FJ, Garcia-Casado Z, Juan MJ, Sanchez AB, Segura A, Santaballa A, Chirivella I, Llop M, Perez G, Barragan E, Salas D, Bolufer P, 2015, Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine. Am J Cancer Res 5(7):2330–2343
Holm K, Hegardt C, Staaf J, Vallon-Christersson J, Jonsson G, Olsson H, Borg A, RingnerM(2010)Molecular subtypes of breast cancer are associated with characteristic DNAmethylation patterns. Breast Cancer Res 12(3):18
Sunami E, Shinozaki M, Sim MS, Nguyen SL, Vu AT, Giuliano AE, Hoon DS, 2008, Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast Cancer Res 10(3):16
Murria Estal R, Palanca Suela S, de Juan Jimenez I, Alenda Gonzalez C, Egoavil Rojas C, Garcia-Casado Z, Lopez Guerrero JA, Juan Fita MJ, Sanchez Heras AB, Segura Huerta A, Santaballa Bertran A, Chirivella Gonzalez I, Llop Garcia M, Perez Simo G, Barragan Gonzalez E, Bolufer Gilabert P, 2016, Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer. Familial Cancer 15(2):193–200
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 937
EP 940
DI 10.1007/s12253-018-0398-4
PG 4
ER
PT J
AU Ponti, G
Maccaferri, M
Mandrioli, M
Manfredini, M
Micali, S
Cotugno, M
Bianchi, G
Ozben, T
Pellacani, G
Del Prete, Ch
Tomasi, A
AF Ponti, Giovanni
Maccaferri, Monia
Mandrioli, Mauro
Manfredini, Marco
Micali, Salvatore
Cotugno, Michele
Bianchi, Giampaolo
Ozben, Tomris
Pellacani, Giovanni
Del Prete, Chiara
Tomasi, Aldo
TI Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Seminal plasma cfDNA; Spermal cfDNA; Prostate cancer; Urological biomarkers; Fluorimetry; Prostate cancer screening; Liquid biopsy
ID Seminal plasma cfDNA; Spermal cfDNA; Prostate cancer; Urological biomarkers; Fluorimetry; Prostate cancer screening; Liquid biopsy
AB Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed. To discover a novel, sensitive, non-invasive biomarker of prostate cancer, through the fluorometric quantification and the electrophoretic analysis of seminal cfDNA in prostate cancer patients compared to healthy individuals. The concentration of seminal plasma cfDNA in prostate cancer patients was 2243.67 ± 1758 ng/μl, compared to 57.7 ± 4.8 ng/μl in healthy individuals (p < 0.05). Electrophoresis sites distribution patterns were different; ladder fragmentation was associated with prostate cancer patients and apoptotic electrophoretic fragmentation with healthy individuals. Human seminal fluid can be a valuable source of cfDNA in the setting of liquid biopsy procedures for the identification of novel oncological biomarkers. Seminal plasma cfDNA in prostate cancer patients is significantly more concentrated than that of age-matched, healthy controls. Fluorometric measurement and electrophoretic assessment allow a reliable quantification and characterization of seminal plasma cfDNA, which can be used routinely in prostate cancer screening programs.
C1 [Ponti, Giovanni] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical PathologyModena, Italy.
[Maccaferri, Monia] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical PathologyModena, Italy.
[Mandrioli, Mauro] University of Modena and Reggio Emilia, Department of Life SciencesModena, Italy.
[Manfredini, Marco] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Dermatology UnitModena, Italy.
[Micali, Salvatore] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Division of UrologyModena, Italy.
[Cotugno, Michele] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Division of UrologyModena, Italy.
[Bianchi, Giampaolo] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Division of UrologyModena, Italy.
[Ozben, Tomris] Akdeniz University, Biochemistry DepartmentAntalya, Turkey.
[Pellacani, Giovanni] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Dermatology UnitModena, Italy.
[Del Prete, Chiara] University of Modena and Reggio Emilia, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Division of UrologyModena, Italy.
[Tomasi, Aldo] University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical PathologyModena, Italy.
RP Ponti, G (reprint author), University of Modena and Reggio Emilia, Department of Diagnostic and Clinical Medicine and Public Health, Division of Clinical Pathology, Modena, Italy.
EM giovanni.ponti@unimore.it
CR Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P, 2001, About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta 313:139–142
Lu JL, Liang ZY, 2016, Circulating free DNA in the era of precision oncology: pre- and post-analytical concerns. Chronic Dis Transl Med 2:223–230
Li HG, Huang SY, Zhou H, Liao AH, Xiong CL, 2009, Quick recovery and characterization of cell-free DNA in seminal plasma of normozoospermia and azoospermia: implications for noninvasive genetic utilities. Asian J Androl 11:703–709
Ponti G, Maccaferri M, Manfredini M, Kaleci S, Mandrioli M, Pellacani G, Ozben T, Depenni R, Bianchi G, Pirola GM, Tomasi A, 2018, The value of fluorimetry, Qubit, and spectrophotometry, NanoDrop, in the quantification of cell-free DNA, cfDNA, in malignant melanoma and prostate cancer patients. Clin Chim Acta 479:14–19
ZagoskinMV, Davis RE, Mukha DV, 2017, Double stranded RNA in human seminal plasma. Front Genet 8(154)
Costa F, Barbisan F, Assmann CE, Araujo NKF, de Oliveira AR, Signori JP, Rogalski F, Bonadiman B, Fernandes MS, da Cruz IBM, 2017, Seminal cell-free DNA levels measured by PicoGreen fluorochrome are associated with sperm fertility criteria. Zygote 25:111–119
Duffy MJ, 2014, PSA in screening for prostate cancer: more good than harm or more harm than good? Adv Clin Chem 66:1–23
G. Ponti M. Maccaferri, M. Manfredini, M. Cotugno, G. Pellacani, A. Conti, S. Micali,M. Mandrioli, A. Tomasi,, 2018, Seminal cellfree DNA molecular profile as a novel diagnostic and prognostic prostate cancer biomarkers. Med Hyph. In press
J. Sambrook E.F. Fritsch, T. Maniatis,, 1989, Molecular Cloning. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press
Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R, 2001, DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61:1659–1665
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 941
EP 945
DI 10.1007/s12253-018-0416-6
PG 5
ER
PT J
AU Danakas, MA
Bsirini, C
Miyamoto, H
AF Danakas, M Alexandra
Bsirini, Caroline
Miyamoto, Hiroshi
TI The Impact of Routine Frozen Section Assessment During Penectomy on Surgical Margin Status and Long-Term Oncologic Outcomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Frozen section assessment; Penile cancer; Penectomy; Prognosis; Surgical margin
ID Frozen section assessment; Penile cancer; Penectomy; Prognosis; Surgical margin
AB No recent studies have focused on assessing the role of intraoperative frozen section assessment (FSA) in the status of surgical margins (SMs) relating to the outcomes of penectomy cases. In this study, we investigated the utility of routine FSA of the SMs in men undergoing penectomy. A retrospective review identified consecutive patients who underwent partial (n = 26) or total (n = 12) penectomy for penile squamous cell carcinoma at our institution from 2004 to 2015. FSA of the SMs was performed in 21 (80.8%) partial and 10 (83.3%) total penectomies. FSAs were reported as positive (n = 3, 9.7%), atypical (n = 3, 9.7%), and negative (n = 25, 80.6%). All of the positive or negative FSA diagnoses were confirmed accurate on the frozen section controls, whereas the 3 cases with atypical FSA had non-malignant, atypical, and carcinoma cells, respectively, on the controls. Final SMs were positive in 6 (15.8%) penectomies, including 4 (12.9%) FSA cases versus 2 (28.6%) non-FSA cases (P = 0.569). Furthermore, initial positive (1 of 3) and atypical (3 of 3) FSA cases achieved negative conversion by excision of additional tissue sent for FSA. Kaplan-Meier analysis revealed that performing FSA or its number/diagnosis was not significantly associated with disease progression. Thus, performing FSA during penectomy does not appear to have any significant impact on final SM status nor long-term oncologic outcomes. However, as seen in at least 4 cases, select patients may benefit from the routine FSA.
C1 [Danakas, M Alexandra] University of Rochester Medical Center, Department of Pathology & Laboratory Medicine, 601 Elmwood Avenue, 14642 Rochester, NY, USA.
[Bsirini, Caroline] University of Rochester Medical Center, Department of Pathology & Laboratory Medicine, 601 Elmwood Avenue, 14642 Rochester, NY, USA.
[Miyamoto, Hiroshi] University of Rochester Medical Center, Department of Pathology & Laboratory Medicine, 601 Elmwood Avenue, 14642 Rochester, NY, USA.
RP Miyamoto, H (reprint author), University of Rochester Medical Center, Department of Pathology & Laboratory Medicine, 14642 Rochester, USA.
EM hiroshi_miyamoto@urmc.rochester.edu
CR Baldur-Felskov B, Hannibal CG, Munk C, Kjaer SK, 2012, Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008: a nationwide population-based study. Cancer Causes Control 23:273–280
Hakenberg OW, Comperat EM, Minhas S, Necchi A, Protzel C, Watkin N, European Association of Urology, 2015, EAU guidelines on penile cancer: 2014 update. Eur Urol 67:142–150
Philippou P, Shabbir M,Malone P, Nigam R,Muneer A, Ralph DJ, Minhas S, 2012, Conservative surgery for squamous cell carcinoma of the penis: resection margins and long-term oncological control. J Urol 188:803–808
Kakiuchi Y, Choy B, Gordetsky J, Izumi K, Wu G, Rashid H, Joseph JV, Miyamoto H, 2013, Role of frozen section analysis of surgical margins during robot-assisted laparoscopic radical prostatectomy: a 2,608-case experience. Hum Pathol 44:1556– 1562
Venigalla S, Wu G, Miyamoto H, 2013, The impact of routine frozen section analysis during partial nephrectomy on surgical margin status and tumor recurrence: A clinicopathologic study of 433 cases. Clin Genitourin Cancer 11:527–536
Miyamoto H, 2017, Clinical benefits of frozen section assessment during urological surgery: does it contribute to improving surgical margin status and patient outcomes as previously thought? Int J Urol 24:25–31
Shen SS, Truong LD, Ro JY, Ayala AG, 2012, Use of frozen section in genitourinary pathology. Pathology 44:427–433
Algaba F, Arce Y, Lopez-Beltran A, Montironi R, Mikuz G, Bono AV, European Society of Uropathology, Uropathology Working Group, 2005, Intraoperative frozen section diagnosis in urological oncology. Eur Urol 47:129–136
Bissada NK, Yakout HH, Fahmy WE, Gayed MS, Touijer AK, Greene GF, Hanash KA, 2003, Multi-institutional long-term experience with conservative surgery for invasive penile carcinoma. J Urol 169:500–502
Minhas S, Kayes O, Hegarty P, Kumar P, Freeman A, Ralph D, 2005, What surgical resection margins are required to achieve oncological control in men with primary penile cancer? BJU Int 96:1040–1043
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 947
EP 950
DI 10.1007/s12253-018-0439-z
PG 4
ER
PT J
AU Zhu, L
Zhang, Sh
Xun, Y
Jiang, Y
Xia, B
Chen, X
Wang, L
Jiang, H
Shenglin, M
AF Zhu, Lucheng
Zhang, Shirong
Xun, Yanping
Jiang, Yanping
Xia, Bing
Chen, Xueqin
Wang, Limin
Jiang, Hong
Shenglin, Ma
TI Correction to: Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Correction to: Pathology & Oncology Research https://doi.org/10.1007/s12253-017-0286-3 The original version of this article unfortunately contained an error in the author group and affiliation sections. The affiliation of first author (Lucheng Zhu) should be Department of Oncology, Hangzhou Cancer Hospital and Department of Oncology, Hangzhou First People’s Hospital, Nanjing Medical University. The corrected author group is shown above and the corrected affiliations are shown below.
C1 [Zhu, Lucheng] Hangzhou Cancer Hospital, Department of OncologyHangzhou, China.
[Zhang, Shirong] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Xun, Yanping] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Jiang, Yanping] Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou Translational Medicine Research CenterNanjing, China.
[Xia, Bing] Hangzhou Cancer Hospital, Department of OncologyHangzhou, China.
[Chen, Xueqin] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
[Wang, Limin] Nanjing Medical University, Hangzhou First People’s Hospital, Department of RespiratoryNanjing, China.
[Jiang, Hong] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Thoracic SurgeryNanjing, China.
[Shenglin, Ma] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
RP Shenglin, M (reprint author), Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, Nanjing, China.
EM mashenglin@medmail.com.cn
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2018
VL 24
IS 4
BP 951
EP 951
DI 10.1007/s12253-018-0421-9
PG 1
ER
PT J
AU Chen, W
Ye, L
Wen, D
Chen, F
AF Chen, Weiqing
Ye, Lijun
Wen, Dengcheng
Chen, Feihua
TI MiR-490-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Migration and Invasion by Directly Regulating ROBO1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Hep3B; MiR-490-5p; ROBO1
ID Hepatocellular carcinoma; Hep3B; MiR-490-5p; ROBO1
AB Studies have investigated the effect of ROBO1. All the same, the relationship between miR-490-5p and ROBO1, and the underlying mechanism are still unclear. We aimed to study the effect of microRNA-490-5p (miR-490-5p) on hepatocellular carcinoma (HCC) cell proliferation, migration and invasion by directly regulating ROBO1. The expression of miR-490-5p and ROBO1 in HCC tissues and cells were tested by RT-qPCR, and the Hep3B cells were selected for subsequent experiments. We confirmed the relationship between miR-490-5p and ROBO1 by luciferase reporter system. The effects of miR-490-5p on cell proliferation, migration and invasion of Hep3B cells were assessed by MTT assay, colony formation assay, wound healing assay and transwell assay, respectively. Flow cytometry was employed to detect the influence of miR-490-5p on cell cycle and apoptosis of Hep3B cells. The expression of miR-490-5p was down-regulated, while ROBO1 was up-regulated in HCC tissues and cells than the controls. MiR-490-5p can target ROBO1. MiR-490-5p inhibited cell proliferation, migration and invasion, but promoted cell apoptosis of Hep3B cells by inhibiting ROBO1.We confirmed that miR-490-5p could directly suppress ROBO1, which might be a potential mechanism in inhibiting HCC cell proliferation, migration and invasion.
C1 [Chen, Weiqing] The People’s Hospital of Lin’an City, Department of General Surgery, No 548 Yijing Street, Jincheng town, 311300 Lin’an, Zhejiang Province, China.
[Ye, Lijun] The People’s Hospital of Lin’an City, Department of Gynecology and Obstetrics, No 548 Yijing Street, Jincheng town, 311300 Lin’an, Zhejiang Province, China.
[Wen, Dengcheng] The People’s Hospital of Lin’an City, Department of General Surgery, No 548 Yijing Street, Jincheng town, 311300 Lin’an, Zhejiang Province, China.
[Chen, Feihua] The People’s Hospital of Lin’an City, Department of Gynecology and Obstetrics, No 548 Yijing Street, Jincheng town, 311300 Lin’an, Zhejiang Province, China.
RP Chen, F (reprint author), The People’s Hospital of Lin’an City, Department of Gynecology and Obstetrics, 311300 Lin’an, China.
EM jxwang3188@163.com
CR Chuang KH, Whitney-Miller CL, Chu CY, Zhou Z, Dokus MK, Schmit S, Barry CT, 2015, MicroRNA-494 is a master epigenetic regulator of multiple invasion-suppressor microRNAs by targeting ten eleven translocation 1 in invasive human hepatocellular carcinoma tumors. Hepatology, Baltimore, Md, 62(2):466–480. https:// doi.org/10.1002/hep.27816
Allen MD, Luong P, Hudson C, Leyton J, Delage B, Ghazaly E, Cutts R, Yuan M, Syed N, Lo Nigro C, Lattanzio L, Chmielewska- Kassassir M, Tomlinson I, Roylance R, Whitaker HC, Warren AY, Neal D, Frezza C, Beltran L, Jones LJ, Chelala C, Wu BW, Bomalaski JS, Jackson RC, Lu YJ, Crook T, Lemoine NR, Mather S, Foster J, Sosabowski J, Avril N, Li CF, Szlosarek PW, 2014, Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging. Cancer Res 74(3):896–907. , DOI 10.1158/ 0008-5472.CAN-13-1702
Chinn GA, Hirokawa KE, Chuang TM, Urbina C, Patel F, Fong J, Funatsu N, Monuki ES, 2015, Agenesis of the corpus callosum due to defective glial wedge formation in Lhx2 mutant mice. Cereb Cortex 25(9):2707–2718. , DOI 10.1093/cercor/bhu067
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 1
EP 9
DI 10.1007/s12253-017-0305-4
PG 9
ER
PT J
AU Delsin, EL
Roberto, MG
Fedatto, P
Engel, EE
Scrideli, AC
Tone, GL
Brassesco, SM
AF Delsin, Elis Lara
Roberto, Molinari Gabriela
Fedatto, F. Paola
Engel, Eduard Edgard
Scrideli, Alberto Carlos
Tone, Gonzaga Luiz
Brassesco, Sol Maria
TI Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNAs; Adhesion; Osteosarcoma; Metastasis
ID microRNAs; Adhesion; Osteosarcoma; Metastasis
AB miRNAs have been identified as key regulators of almost all cellular processes, therefore, their dysregulation is involved with several diseases, including cancer. miRNAs specifically related to the metastastic cascade are called metastamiRs and can be involvedwith different steps of this process, including loss of adhesion. Osteosarcoma (OS) is the most common primary malignant pediatric bone tumor that often presents metastatic disease at diagnosis; therefore, a deeper study of adhesionassociated miRNAs could shed light on its pathophysiology. Online databases were used to select four miRNAs (miR-139; miR-181b; miR-584; miR-708) predicted or validated to target proteins related to adherent junctions and focal adhesion pathways, and their expression levels and possible associations with clinical features evaluated in primary OS samples. Our results showed downregulation of miR-139-5p and miR-708-5p in OS samples compared to non-neoplastic controls. Moreover, lower expression of miR-708-5p was associated with poor overall survival and higher expression of miR-181b-5p related to worst chemotherapy response (low HUVOS level). Based on these results, we selected miR-139-5p and miR-708-5p for further functional testing. Inducing the expression of miR-139-5p diminished the clonogenic capacity of the HOS cell line, while upregulation of miR-708-5p was related to a lower cellular adhesion. In summary, this work identified new signatures of microRNA dysregulation that may serve as useful prognostic markers in this aggressive pediatric bone tumor.
C1 [Delsin, Elis Lara] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of GeneticsSao Paulo, Brazil.
[Roberto, Molinari Gabriela] University of Sao Paulo, Ribeirao Preto School of Medicine, Regional Blood CenterSao Paulo, Brazil.
[Fedatto, F. Paola] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Engel, Eduard Edgard] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
[Scrideli, Alberto Carlos] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Tone, Gonzaga Luiz] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Brassesco, Sol Maria] University of Sao Paulo, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, Department of BiologySao Paulo, Brazil.
RP Brassesco, SM (reprint author), University of Sao Paulo, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, Department of Biology, Sao Paulo, Brazil.
EM solbrassesco@usp.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 11
EP 20
DI 10.1007/s12253-017-0316-1
PG 10
ER
PT J
AU Nagy,
Garzuly, F
Padanyi, G
Szucs, I
Feldmann,
Murnyak, B
Hortobagyi, T
Kalman, B
AF Nagy, Adam
Garzuly, Ferenc
Padanyi, Gergely
Szucs, Ivan
Feldmann, Adam
Murnyak, Balazs
Hortobagyi, Tibor
Kalman, Bernadette
TI Molecular Subgroups of Glioblastoma– an Assessment by Immunohistochemical Markers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; Molecular subgroups; Translation; Clinical setting
ID Glioblastoma; Molecular subgroups; Translation; Clinical setting
AB Comprehensive molecular characterization of and novel therapeutic approaches to glioblastoma have been explored as a result of advancements in biotechnologies. In this study, we aimed to bring basic research discoveries closer to clinical practice and ultimately incorporate molecular classification into the routine histopathological evaluation of grade IV gliomas. Integrated results of genome-wide sequencing, transcriptomic and epigenomic analyses by The Cancer Genome Atlas Network defined the classic, proneural, neural and mesenchymal subtypes of this tumor. In a retrospective cohort, we analyzed selected subgroup-defining molecular markers in formalin-fixed paraffin-embedded surgical specimens by immunohistochemistry. Quantitative and qualitative scores of marker expression were tested in hierarchical cluster analyses to evaluate segregations of the molecular subgroups, which then were correlated with clinical parameters including patients’ age, gender and overall survival. Our study has confirmed the separation of molecular glioblastoma subgroups with clear trends regarding clinical correlations. Future analyses in a larger, prospective cohort using similar methods are expected to facilitate the development of a molecular diagnostic panel that may complement routine histological work up and support prognostication as well as treatment decisions in glioblastoma.
C1 [Nagy, Adam] University of Pecs, Faculty of Medicine, Department of Public HealthPecs, Hungary.
[Garzuly, Ferenc] Vas County Markusovszky Hospital, 9700 Szombathely, Hungary.
[Padanyi, Gergely] Vas County Markusovszky Hospital, 9700 Szombathely, Hungary.
[Szucs, Ivan] St Borbala Hospital, Faculty of Medicine, Institute of Behavioral SciencesTatabanya, Hungary.
[Feldmann, Adam] University of PecsPecs, Hungary.
[Murnyak, Balazs] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Hortobagyi, Tibor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Kalman, Bernadette] University of Pecs, Faculty of Medicine, Department of Public HealthPecs, Hungary.
RP Kalman, B (reprint author), University of Pecs, Faculty of Medicine, Department of Public Health, Pecs, Hungary.
EM bernadett.kalman@etk.pte.hu;kalman.bernadett@markusovszky.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 21
EP 31
DI 10.1007/s12253-017-0311-6
PG 11
ER
PT J
AU Singh, AS
Ghosh, KS
AF Singh, Anil Seram
Ghosh, Kumar Sankar
TI Metabolic Phase I (CYPs) and Phase II (GSTs) Gene Polymorphisms and Their Interaction with Environmental Factors in Nasopharyngeal Cancer from the Ethnic Population of Northeast India
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nasopharyngeal carcinoma (NPC); Polymorphisms in metabolizing genes; Gene-gene interaction; Tobacco smokers and chewers; Gene-environment interaction; Northeast India
ID Nasopharyngeal carcinoma (NPC); Polymorphisms in metabolizing genes; Gene-gene interaction; Tobacco smokers and chewers; Gene-environment interaction; Northeast India
AB Multiple genetic and environmental factors and their interaction are believed to contribute in the pathogenesis of Nasopharyngeal Cancer (NPC). We investigate the role of Metabolic Phase I (CYPs) and Phase II (GSTs) gene polymorphisms, gene-gene and gene-environmental interaction in modulating the susceptibility to NPC in Northeast India. To determine the association of metabolic gene polymorphisms and environmental habits, 123 cases and 189 controls blood/ swab samples were used for PCR and confirmed by Sanger sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. The T3801C in the 3′- flanking region of CYP1A1 gene was detected by PCR-RFLP method. The Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The GSTM1 null genotype alone (OR = 2.76) was significantly associated with NPC risk (P < 0.0001). The combinations of GSTM1 null and GSTT1 null genotypes also higher, 3.77 fold (P < 0.0001), risk of NPC, while GSTM1 null genotype along with CYP1A1 T3801C TC + CC genotype had 3.22 (P = 0.001) fold risk. The most remarkable risk was seen among individual carrying GSTM1 null, GSTT1 null genotypes and CYP1A1 T3801C TC + CC genotypes (OR = 5.71, P = 0.001). Further; analyses demonstrate an enhanced risk of NPC in smoked meat (OR = 5.56, P < 0.0001) and fermented fish consumers (OR = 5.73, P < 0.0001) carrying GSTM1 null genotype. An elevated risk of NPC was noted in smokers (OR = 12.67, P < 0.0001) and chewers (OR = 5.68, P < 0.0001) with GSTM1 null genotype. However, smokers had the highest risk of NPC among individuals carrying GSTT1 null genotype (OR = 4.46, P = 0.001) or CYP1A1 T3801C TC + CC genotype (OR = 7.13, P < 0.0001). The association of null genotypes and mutations of metabolic neutralizing genes along with the environmental habits (tobacco smokers and chewers, smoke meat, fermented fishes) can be used as a possible biomarker for early detection and preventive measure of NPC.
C1 [Singh, Anil Seram] Assam University, Department of Biotechnology, Molecular Medicine Laboratory, 788011 Silchar, Assam, India.
[Ghosh, Kumar Sankar] Assam University, Department of Biotechnology, Molecular Medicine Laboratory, 788011 Silchar, Assam, India.
RP Ghosh, KS (reprint author), Assam University, Department of Biotechnology, Molecular Medicine Laboratory, 788011 Silchar, India.
EM drsankarghosh@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 33
EP 44
DI 10.1007/s12253-017-0309-0
PG 12
ER
PT J
AU Czirbesz, K
Gorka, E
Balatoni, T
Panczel, G
Melegh, K
Kovacs, P
Gezsi, A
Liszkay, G
AF Czirbesz, Kata
Gorka, Eszter
Balatoni, Timea
Panczel, Gitta
Melegh, Krisztina
Kovacs, Peter
Gezsi, Andras
Liszkay, Gabriella
TI Efficacy of Vemurafenib Treatment in 43 Metastatic Melanoma Patients with BRAF Mutation. Single-Institute Retrospective Analysis, Early Real-Life Survival Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Vemurafenib; Melanoma; LDH level; Targeted therapy; Treatment; Survival
ID Vemurafenib; Melanoma; LDH level; Targeted therapy; Treatment; Survival
AB BRAF inhibitor vemurafenib achieved improved overall survival over chemotherapy and have been approved by the FDA and EMA for the treatment of BRAF-mutated metastatic melanoma. The aim of our retrospective analysis was to determine the efficacy and safety of vemurafenib therapy for BRAF mutated metastatic melanoma and subsequently to prove the clinical benefit for the studied 43 patients, based on real-life data. From November 2012 to October 2015 we have selected 43 BRAF mutated, metastatic melanoma patients, treated with vemurafenib. The median follow-up time was 15.9 months. We evaluated progression free survival (PFS), overall survival (OS) and toxicities. According to the AJCC staging system 70% of the patients had stage M1c metastasis, including 6 with stable brain metastasis. Objective responses were noted in 51.1%, the disease control rate was achieved in 79% of the patients. Complete responses were attained by 5 patients (11.6%). Median PFS was 6.48 (95% CI:4.8–15.0) months, median OS was 11.47 (95% CI:8.08-NA) months. We found significant association between LDH level and OS in univariate (p = 0.000613) and multivariate analysis (p = 0.0168). The most common adverse events (AEs) included follicular hyperkeratosis, rash, arthralgia and photosensitivity. Grade 3 AEs, such as cutaneous squamous-cell carcinoma, QTcB interval prolongation, rash, arthralgia were reported in 7 patients (17%).We had noGrade 4 side effects. Similar to the previously published data our analysis confirms the improved survival with vemurafenib treatment (11.47 months) in patients with BRAF V600 mutation. Vemurafenib therapy was well tolerated, the AE profile was almost consistent with the previously reported data of randomised clinical trials.
C1 [Czirbesz, Kata] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Gorka, Eszter] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Balatoni, Timea] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Panczel, Gitta] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Melegh, Krisztina] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Kovacs, Peter] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
[Gezsi, Andras] Semmelweis University, Department of Genetics, Cell and Immunobiology, Nagyvarad ter 4, H-1089 Budapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of Dermatology, Rath Gyorgy utca 7-9, H-1122 Budapest, Hungary.
RP Czirbesz, K (reprint author), National Institute of Oncology, Department of Dermatology, H-1122 Budapest, Hungary.
EM czirbikatu@gmail.com
CR Siegel RL, Miller KD, Jemal A, 2015, Cancer statistics. CA Cancer J Clin 65:5–29. , DOI 10.3322/caac.21254
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Hodi FS, O'Day SJ, McDermott DF, Weber RW et al, 2010, Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723 Erratum in: N Engl J Med. 363(13):1290
Chapman PB, Hauschild A, Robert C et al, 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516
McArthur GA, Chapman PB, Robert C et al, 2014, Safety and efficacy of vemurafenib in BRAF, V600E, and BRAF, V600K, mutation-positive melanoma, BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 15(3):323–332
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Robert C, Karaszewska B, Schachter J et al, 2015, Improved overall survival in melanoma combined dabrafenib and trametinib. N Engl J Med 372:30–39
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 45
EP 50
DI 10.1007/s12253-017-0324-1
PG 6
ER
PT J
AU Go, H
Kang, JM
Kim, PJ
Lee, JLy
Park, YJ
Park, JM
Ro, YJ
Cho, MY
AF Go, Heounjeong
Kang, Jung Mun
Kim, Pil-Jong
Lee, Jae-Lyun
Park, Y Ji
Park, Ja-Min
Ro, Y Jae
Cho, Mee Yong
TI Development of Response Classifier for Vascular Endothelial Growth Factor Receptor (VEGFR)-Tyrosine Kinase Inhibitor (TKI) in Metastatic Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastatic renal cell carcinoma; Vascular endothelial growth factor signaling; Tyrosine kinase inhibitors; Response classifier; Machine learning
ID Metastatic renal cell carcinoma; Vascular endothelial growth factor signaling; Tyrosine kinase inhibitors; Response classifier; Machine learning
AB Vascular endothelial growth factor receptor (VEGFR)-targeted therapy improved the outcome ofmetastatic renal cell carcinoma (mRCC) patients. However, a prediction of the response to VEGFR-tyrosine kinase inhibitor (TKI) remains to be elucidated. We aimed to develop a classifier for VEGFR-TKI responsiveness in mRCC patients. Among 101 mRCC patients, ones with complete response, partial response, or ≥24 weeks stable disease in response to VEGFR-TKI treatment were defined as clinical benefit group, whereas patients with <24 weeks stable disease or progressive disease were classified as clinical non-benefit group. Clinicolaboratoryhistopathological data, 41 gene mutations, 20 protein expression levels and 1733 miRNA expression levels were compared between clinical benefit and non-benefit groups. The classifier was built using support vector machine (SVM). Seventy-three patients were clinical benefit group, and 28 patients were clinical non-benefit group. Significantly different features between the groups were as follows: age, time from diagnosis to TKI initiation, thrombocytosis, tumor size, pT stage, ISUP grade, sarcomatoid change, necrosis, lymph node metastasis and expression of pAKT, PD-L1, PD-L2, FGFR2, pS6, PDGFRβ, HIF-1α, IL-8, CA9 and miR-421 (all, P < 0.05). A classifier including necrosis, sarcomatoid component and HIF-1α was built with 0.87 accuracy using SVM. When the classifier was checked against all patients, the apparent accuracy was 0.875 (95% CI, 0.782–0.938). The classifier can be presented as a simple decision tree for clinical use. We developed a VEGFR-TKI response classifier based on comprehensive inclusion of clinicolaboratory-histopathological, immunohistochemical, mutation and miRNA features that may help to guide appropriate treatment in mRCC patients.
C1 [Go, Heounjeong] University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.
[Kang, Jung Mun] University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.
[Kim, Pil-Jong] Seoul National University College of Dental Medicine, Biomedical Knowledge Engineering Laboratory, 101 Daehakno, Jongni-gu, 03080 Seoul, South Korea.
[Lee, Jae-Lyun] University of Ulsan College of Medicine, Asan Medical Center, Department of Oncology, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.
[Park, Y Ji] Catholic University of Daegu, School of Medicine, Department of Pathology, 33, Duryugongwon-ro 17-gil, Nam-gu, 42472 Daegu, South Korea.
[Park, Ja-Min] University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.
[Ro, Y Jae] Cornell University, The Methodist Hospital and Weill Medical College, Department of Pathology and Genomic Medicine, 6565 Fannin St, 77030 Houston, TX, USA.
[Cho, Mee Yong] University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.
RP Cho, MY (reprint author), University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, 05505 Seoul, South Korea.
EM yongcho@amc.seoul.kr
CR Srinivasan R, Ricketts CJ, Sourbier C, Linehan WM, 2015, New strategies in renal cell carcinoma: targeting the genetic and metabolic basis of disease. Clinical cancer research : an official journal of the American Association for Cancer Research 21(1):10–17. , DOI 10.1158/1078-0432.CCR-13-2993
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Escudier B, Eisen T, StadlerWM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, GoreM, Freeman S, Schwartz B, ShanM, Simantov R, Bukowski RM, 2007, Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356(2):125–134. , DOI 10.1056/ NEJMoa060655
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 51
EP 58
DI 10.1007/s12253-017-0323-2
PG 8
ER
PT J
AU Aaberg-Jessen, Ch
Fogh, L
Dahl Sorensen, M
Halle, B
Brunner, N
Winther Kristensen, B
AF Aaberg-Jessen, Charlotte
Fogh, Louise
Dahl Sorensen, Mia
Halle, Bo
Brunner, Nils
Winther Kristensen, Bjarne
TI Overexpression of TIMP-1 and Sensitivity to Topoisomerase Inhibitors in Glioblastoma Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma; TIMP-1; TOP inhibitors; Chemosensitivity
ID Glioblastoma; TIMP-1; TOP inhibitors; Chemosensitivity
AB The multifunctional protein - tissue inhibitor of metalloproteinases-1 (TIMP-1) - has been associated with a poor prognosis in several types of cancers including glioblastomas. In addition, TIMP-1 has been associated with decreased response to chemotherapy, and especially the efficacy of the family of topoisomerase (TOP) inhibitors has been related to TIMP-1. As a second line treatment of glioblastomas, the vascular endothelial growth factor (VEGF) antibody bevacizumab is administered in combination with the TOP1 inhibitor irinotecan and glioblastoma cell levels of TIMP-1 could therefore potentially influence the efficacy of such treatment. In the present study, we aimed to investigate whether a high TIMP-1 expression in glioblastoma cell lines would affect the sensitivity to TOP inhibitors, and whether TIMP-1 overexpressing cells would have alterered growth and invasion. We established TIMP-1 overexpressing subclones from two human glioblastoma cell lines. TIMP-1 overexpressing U87MG cells were significantly more resistant than low TIMP-1 expressing clones and parental cells when exposed to SN-38 (TOP1 inhibitor) or epirubicin (TOP2 inhibitor). No significant differences were observed for the TIMP-1 transfected A172 cells. Implantation of both U87MG and A172 spheroids into organotypic brain slice cultures revealed a reduced growth of TIMP-1 overexpressing U87MG spheroids, however, no significant differences in invasion were observed. The present study suggests that TIMP-1 overexpression reduces the effect of TOP inhibitors in glioblastoma. TIMP-1 also appeared to reduce spheroid growth, but did not influence invasion. Whether TIMP-1 plays a role in irinotecan resistance and has a predictive potential in glioblastoma patients remains to be elucidated.
C1 [Aaberg-Jessen, Charlotte] Odense University Hospital, Department of Pathology, J.B. Winsloew vej 15, DK-5000 Odense, Denmark.
[Fogh, Louise] University of Copenhagen, Faculty of Health and Medical Sciences, Institute for Drug Design and Pharmacology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
[Dahl Sorensen, Mia] Odense University Hospital, Department of Pathology, J.B. Winsloew vej 15, DK-5000 Odense, Denmark.
[Halle, Bo] Odense University Hospital, Department of Pathology, J.B. Winsloew vej 15, DK-5000 Odense, Denmark.
[Brunner, Nils] University of Copenhagen, Faculty of Health and Medical Sciences, Institute for Drug Design and Pharmacology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
[Winther Kristensen, Bjarne] Odense University Hospital, Department of Pathology, J.B. Winsloew vej 15, DK-5000 Odense, Denmark.
RP Winther Kristensen, B (reprint author), Odense University Hospital, Department of Pathology, DK-5000 Odense, Denmark.
EM bjarne.winther.kristensen@rsyd.dk
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 59
EP 69
DI 10.1007/s12253-017-0312-5
PG 11
ER
PT J
AU Wang, Y
Yan, Z
Lu, Q
Wang, Y
Sun, X
Zhang, Sh
AF Wang, Yuandong
Yan, Zhang
Lu, Qian
Wang, Yiming
Sun, Xinchen
Zhang, Shu
TI NRG-1 Stimulates Serum DJ-1 Increase in Breast Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serum DJ-1; HER3; NRG-1; Breast cancers; MCF-7 cells
ID Serum DJ-1; HER3; NRG-1; Breast cancers; MCF-7 cells
AB To explore the relationship between the expression of DJ-1/HER3 and tumor grade in breast cancer, and investigate the effect of HER3 on NRG-1-mediated serum DJ-1 level in vivo.We analyze the expression level of DJ-1 and HER3 in 68 patients with different grades of breast cancer by immunostaining the tissue microarray. Besides, we investigated the serum DJ-1 level by ELISA. We found that the detectable DJ-1 protein expression is decreased, and the HER3 expression is increased in tumor tissue with the progression of breast cancer. There is a significant rise of DJ-1 in serumin vivo with the stimulation of NRG-1. Meanwhile, we found that HER3 knockdown abolishes NRG-1-induced serum DJ-1 increase and HER3 overexpress improves NRG-1-induced serum DJ- 1 increase. This study provides a serum biomarker for breast cancer. The results showed that DJ-1 was associated with clinical stage of breast cancer, and NRG-1 increased the dissociation of HER3 and DJ-1, with promoting the level of DJ-1 in peripheral blood. It is suggested that the level of DJ-1 in peripheral blood may be conducive to assess the prognosis of patients with breast cancer and serum DJ-1 levels can serve as an indicator of therapeutic effectiveness for the development of HER3 targeting breast cancer antibody therapies.
C1 [Wang, Yuandong] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, Jiangsu, China.
[Yan, Zhang] Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Department of Anesthesiology, 430022 Wuhan, Hubei, China.
[Lu, Qian] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, Jiangsu, China.
[Wang, Yiming] University of New South Wales, School of Biotechnology and Biomolecular Sciences, Kensington, 2052 Sydney, NSW, Australia.
[Sun, Xinchen] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, Jiangsu, China.
[Zhang, Shu] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 300 Guangzhou Road, 210029 Nanjing, Jiangsu, China.
RP Zhang, Sh (reprint author), The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210029 Nanjing, China.
EM zhangshu@njmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 71
EP 79
DI 10.1007/s12253-017-0326-z
PG 9
ER
PT J
AU Davidson, TK
Zhu, Z
Bai, Q
Xiao, H
Wakefield, RM
Fang, Y
AF Davidson, T Kristoffer
Zhu, Ziwen
Bai, Qian
Xiao, Huaping
Wakefield, R Mark
Fang, Yujiang
TI Blueberry as a Potential Radiosensitizer for Treating Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Blueberry extract; Radiation; Apoptosis; Cervical cancer
ID Blueberry extract; Radiation; Apoptosis; Cervical cancer
AB Cervical cancer (CC) is a leading cause of death in women worldwide. Radiation therapy (RT) for CC is an effective alternative, but its toxicity remains challenging. Blueberry is amongst the most commonly consumed berries in the United States.We previously showed that resveratrol, a compound in red grapes, can be used as a radiosensitizer for prostate cancer. In this study, we found that the percentage of colonies, PCNA expression level and the OD value of cells from the CC cell line SiHa were all decreased in RT/Blueberry Extract (BE) group when compared to those in the RT alone group. Furthermore, TUNEL+ cells and the relative caspase-3 activity in the CC cells were increased in the RT/BE group compared to those in the RT alone group. The antiproliferative effect of RT/BE on cancer cells correlated with downregulation of pro-proliferative molecules cyclin D and cyclin E. The pro-apoptotic effect of RT/BE correlated with upregulation of the pro-apoptotic molecule TRAIL. Thus, BE sensitizes SiHa cells to RT by inhibition of proliferation and promotion of apoptosis, suggesting that blueberry might be used as a potential radiosensitizer to treat CC.
C1 [Davidson, T Kristoffer] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Bai, Qian] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Xiao, Huaping] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Wakefield, R Mark] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
EM yujiang.fang@dmu.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 81
EP 88
DI 10.1007/s12253-017-0319-y
PG 8
ER
PT J
AU Sun, Ch
Ding, Y
Wang, Sh
Hu, W
AF Sun, Cheng
Ding, Yangyang
Wang, Shimin
Hu, Wei
TI Long Non-Coding RNA SPRY4-IT1 Can Predict Poor Prognosis in Digestive System Malignancies: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lncRNA; SPRY4-IT1; Prognosis; Metastasis; Meta-analysis
ID lncRNA; SPRY4-IT1; Prognosis; Metastasis; Meta-analysis
AB Recent studies have reported that long non-coding RNA SPRY4 intron transcript 1 (SPRY4-IT1) is abnormally expressed in malignant digestive tumors and associated with prognosis. But its clinical relevance is unclear. Here, we performed a meta-analysis aims to evaluate the prognostic value of SPRY4-IT1 in digestive system malignancies. We systematic search the PubMed, Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to explored the association of lncRNA SPRY4-IT1 with prognosis. Five studies were eligible for analysis, a total of 518 patients were included. Meta-analysis indicated that overexpression of SPRY4-IT1 was associated with poor over survival (OS) (HR = 1.24, 95% CI:0.49–1.98; random-effects model). The clinicopathological parameters analysis further showed that increased expression level of SPRY4-IT1 was positively correlated with lymph node metastasis (HR = 1.45, 95% CI =0.88–2.02; fixed-effects model), TNM stage (HR = 1.24,95% CI = 0.78–1.70; fixed-effects model), and invasion depth (HR = 1.25,95% CI = 0.63–1.88; fixed-effects model). lncRNA SPRY4-IT1 may serve as a potential prognostic marker in malignant digestive tumors.
C1 [Sun, Cheng] The Second Hospital of Anhui Medical University, Department of PharmacologyHefei, Anhui, China.
[Ding, Yangyang] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
[Wang, Shimin] The Second Hospital of Anhui Medical University, Department of PharmacologyHefei, Anhui, China.
[Hu, Wei] The Second Hospital of Anhui Medical University, Department of PharmacologyHefei, Anhui, China.
RP Hu, W (reprint author), The Second Hospital of Anhui Medical University, Department of Pharmacology, Hefei, China.
EM scadyy@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 89
EP 95
DI 10.1007/s12253-017-0327-y
PG 7
ER
PT J
AU Nagy, BZs
Bartak, KB
Kalmar, A
Galamb, O
Wichmann, B
Dank, M
Igaz, P
Tulassay, Zs
Molnar, B
AF Nagy, Brigitta Zsofia
Bartak, Kinga Barbara
Kalmar, Alexandra
Galamb, Orsolya
Wichmann, Barnabas
Dank, Magdolna
Igaz, Peter
Tulassay, Zsolt
Molnar, Bela
TI Comparison of Circulating miRNAs Expression Alterations in Matched Tissue and Plasma Samples During Colorectal Cancer Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNA; Plasma; Circulating microRNA; Colorectal cancer; Colorectal adenoma; Microarray; Real-time PCR; Tissue
ID microRNA; Plasma; Circulating microRNA; Colorectal cancer; Colorectal adenoma; Microarray; Real-time PCR; Tissue
AB MicroRNAs (miRNAs) have been found to play a critical role in colorectal adenoma-carcinoma sequence. MiRNA-specific high-throughput arrays became available to detect promising miRNA expression alterations even in biological fluids, such as plasma samples, where miRNAs are stable. The purpose of this study was to identify circulating miRNAs showing altered expression between normal colonic (N), tubular adenoma (ADT), tubulovillous adenoma (ADTV) and colorectal cancer (CRC) matched plasma and tissue samples. Sixteen peripheral plasma and matched tissue biopsy samples (N n = 4; ADT n = 4; ADTV n = 4; CRC n = 4) were selected, and total RNA including miRNA fraction was isolated. MiRNAs from plasma samples were extracted using QIAamp Circulating Nucleic Acid Kit (Qiagen). Matched tissue-plasma miRNA microarray experiments were conducted by GeneChip® miRNA 3.0 Array (Affymetrix). RT-qPCR (microRNA Ready-to-use PCR Human Panel I + II; Exiqon) was used for validation. Characteristic miRNA expression alterations were observed in comparison of AD and CRC groups (miR-149*, miR-3196, miR-4687) in plasma samples. In the N vs. CRC comparison, significant overexpression of miR-612, miR-1296, miR-933, miR-937 and miR-1207 was detected by RT-PCR (p < 0.05). Similar expression pattern of these miRNAs were observed using microarray in tissue pairs, as well. Although miRNAs were also found in circulatory system in a lower concentration compared to tissues, expression patterns slightly overlapped between tissue and plasma samples. Detected circulating miRNA alterations may originate not only from the primer tumor but from other cell types including immune cells.
C1 [Nagy, Brigitta Zsofia] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Bartak, Kinga Barbara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Galamb, Orsolya] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Wichmann, Barnabas] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of OncologyBudapest, Hungary.
[Igaz, Peter] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
RP Nagy, BZs (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM nagyzsofiab@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 97
EP 105
DI 10.1007/s12253-017-0308-1
PG 9
ER
PT J
AU Ozgoz, A
Ozturk, HK
Yukselturk, A
Samli, H
Baskan, Z
Icduygu, MF
Bacaksiz, M
AF Ozgoz, Asuman
Ozturk, Hekimler Kuyas
Yukselturk, Aysegul
Samli, Hale
Baskan, Zuhal
Icduygu, Mutlu Fadime
Bacaksiz, Mehmet
TI Genetic Variations of DNA Repair Genes in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; DNA damage; DNA repair; Polymorphism
ID Breast cancer; DNA damage; DNA repair; Polymorphism
AB Genetic variations in DNA repair genes may affect DNA repair capacity therefore increase risk for cancer. In our study, we evaluted the relation between DNA repair gene polymorphisms XRCC1 rs1799782, rs25487, rs25489; XPC rs2228000, rs2228001; XPD rs1799793, rs13181; XRCC3 rs861539; RAD51B rs10483813, rs1314913 and breast cancer risk for 202 Turkish cases in total, in which 102 patients with breast cancer and 100 controls. Genotyping of the DNA samples was carried out by multiplex PCR andmatrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) using Sequenom MassARRAY 4 analyzer. Genotype and allele distributions were calculated between the groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. rs25487 AA genotype and A allele was found to be increased in the control group (respectively, OR 0.16 95% CI 0.02–1.06, p = 0.058; OR 1.55, 95% CI 1.01–2.36, p = 0.043) and rs861539 T allele was found to be decreased in the patient group (OR 1.53, 95% CI 1.01–2.30, p = 0.049). No association with breast cancer was found for the remaining SNPs. Our findings suggest that XRCC1 rs25487 AA genotype and A allele, XRCC3 rs861539 Tallelemay have protective effects in breast cancer for Turkish population.
C1 [Ozgoz, Asuman] Kastamonu University, Kastamonu School of Medicine, Department of Medical Genetics, Kuzeykent Mah, Orgeneral Atilla Ates Pasa Cd. No: 19 C, 37200 Kastamonu, Turkey.
[Ozturk, Hekimler Kuyas] Suleyman Demirel University, School of Medicine, Department of Medical GeneticsIsparta, Turkey.
[Yukselturk, Aysegul] Kastamonu University, Fazil Boyner Faculty of Health Sciences, Department of Nutrition and DieteticsKastamonu, Turkey.
[Samli, Hale] Uludag University, School of Veterinary Medicine, Department of GeneticsBursa, Turkey.
[Baskan, Zuhal] Acibadem University, School of Medicine, Department of Medical OncologyIstanbul, Turkey.
[Icduygu, Mutlu Fadime] Giresun University, School of Medicine, Department of Medical GeneticsGiresun, Turkey.
[Bacaksiz, Mehmet] Alanya Ciplakli Family Health CenterAlanya-Antalya, Turkey.
RP Ozgoz, A (reprint author), Kastamonu University, Kastamonu School of Medicine, Department of Medical Genetics, 37200 Kastamonu, Turkey.
EM biologistasu@gmail.com
CR Deligezer U, Dalay N, 2004, Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients. Exp Mol Med 36(6):572–575
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 107
EP 114
DI 10.1007/s12253-017-0322-3
PG 8
ER
PT J
AU Li, J
Liu, Y
Xue, J
Xu, M
Zhang, J
Liu, J
Wang, W
AF Li, Jianchao
Liu, Yifei
Xue, Jianhua
Xu, Mingming
Zhang, Jianguo
Liu, Junhua
Wang, Wenyi
TI Kruppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kruppel-like factor 8; Non-small cell lungcancer; Pithelial-mesenchymal transition; Prognosis
ID Kruppel-like factor 8; Non-small cell lungcancer; Pithelial-mesenchymal transition; Prognosis
AB Kruppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR,Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.
C1 [Li, Jianchao] the First People’s Hospital of Yancheng, Department of Thoracic surgery, 166 Yulongxi Road, 224006 Yancheng, Jiangsu, China.
[Liu, Yifei] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, Jiangsu, China.
[Xue, Jianhua] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Xu, Mingming] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Zhang, Jianguo] Affiliated Hospital of Nantong University, Pathology Medicine Center, 226001 Nantong, Jiangsu, China.
[Liu, Junhua] Affiliated Hospital of Nantong University, Department of Thoracic Surgery, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
[Wang, Wenyi] the First People’s Hospital of Yancheng, Department of Thoracic surgery, 166 Yulongxi Road, 224006 Yancheng, Jiangsu, China.
RP Wang, W (reprint author), the First People’s Hospital of Yancheng, Department of Thoracic surgery, 224006 Yancheng, China.
EM 420002318@qq.com
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Soltermann A et al, 2008, Prognostic significance of epithelialmesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res 14(22): 7430–7437
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 115
EP 121
DI 10.1007/s12253-017-0321-4
PG 7
ER
PT J
AU Park, YJ
Hong, D
Park, YJ
AF Park, Y Ji
Hong, Daegy
Park, Young Ji
TI Association between Morphological Patterns of Myometrial Invasion and Cancer Stem Cell Markers in Endometrial Endometrioid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer stem cell marker; Epithelial-to-mesenchymal transition; Endometrioid carcinoma; Myometrial invasion
ID Cancer stem cell marker; Epithelial-to-mesenchymal transition; Endometrioid carcinoma; Myometrial invasion
AB In endometrial endometrioid adenocarcinoma (EEC), the depth of myometrial invasion (MI) is an important parameter for determining whether additional treatment is warranted. The present study investigated the association between MI patterns, cancer stem cell (CSC) phenotypes, and their clinicopathological significance in EEC. A total of 73 cases of EEC with MI were examined in this study. Haematoxylin and eosin-stained tissue specimens were analysed for MI pattern, which was categorised as infiltrating; expansile; adenomyosis (AM)-like; or microcystic, elongated, and fragmented (MELF)-type. The expression of CSC markers such as cluster of differentiation (CD)44, CD133, and Nanog1, as well as oestrogen receptor (ER) and progesterone receptor (PR) was examined by immunohistochemistry. Clinicopathological features including age, DOI, MI pattern, LVI, lymph node (LN) metastasis, disease progression, and survival outcome were recorded. Most examined cases (45/73) were International Federation of Gynecology and Obstetrics (FIGO) stage I. MI showed infiltrating (49.3%), AM-like (26.3%), MELF (15.1%), and expansile (9.6%) patterns. Tumours with the infiltrating pattern were associated with high FIGO grade (P = 0.002), reduced ER and PR, and CD44 expression (P = 0.014, 0.026, and 0.030, respectively); those with a MELF pattern showed LN metastasis (P < 0.001), lymphovascular invasion (P = 0.011), and reduced ER, CD44, and CD133 expression (P = 0.036, 0.006, and 0.016, respectively). EEC with infiltrating/MELF patterns of MI is associated with worse prognosis. These results suggest that CSC expression profiles are an unfavourable indicator of EEC.
C1 [Park, Y Ji] Catholic University of Daegu, School of Medicine, Department of PathologyDaegu, South Korea.
[Hong, Daegy] Kyungpook National University School of Medicine, Kyungpook National University Medical Center, Gynecologic Cancer CenterDaegu, South Korea.
[Park, Young Ji] Kyungpook National University School of Medicine, Kyungpook National University Medical Center, Department of Pathology, 807 Hoguk-ro, Buk-gu, 41404 Daegu, South Korea.
RP Park, YJ (reprint author), Kyungpook National University School of Medicine, Kyungpook National University Medical Center, Department of Pathology, 41404 Daegu, South Korea.
EM jyparkmd@knu.ac.kr
CR Cole AJ, Quick CM, 2013, Patterns of myoinvasion in endometrial adenocarcinoma: recognition and implications. Adv Anat Pathol 20(3):141–147
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ClarkeMF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Wahl GM, 2006, Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344
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Mirantes C, Espinosa I, Ferrer I, Eaton EN, Ayyanan A, Zhou AY, Weinberg RA, 2013, Epithelial-to-mesenchymal transition and stem cells in endometrial cancer. Hum Pathol 44(10):1973–1981
Hollier BG, Evans K, Mani SA The epithelial-to-mesenchymal transition and cancer stemcells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia 14(1):29–43
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Dai D, Wolf DM, Litman ES, White MJ, Leslie KK, 2002, Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res 62(3):881–886
Hanekamp EE, Kuhne EC, Smid-Koopman E, Chadha-Ajwani S, Huikeshoven FJ, Burger CW, Blok LJ, 2002, Loss of progesterone receptor may lead to an invasive phenotype in human endometrial cancer. Eur J Cancer 38(Suppl 6):S71–SS2
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 123
EP 130
DI 10.1007/s12253-017-0320-5
PG 8
ER
PT J
AU Nemeth, Zs
Boer, K
Borbely, K
AF Nemeth, Zsuzsanna
Boer, Katalin
Borbely, Katalin
TI Advantages of 18F FDG-PET/CT over Conventional Staging for Sarcoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 18F–FDG pet/Ct; Standardized uptake value; Imaging modalities; Sarcoma
ID 18F–FDG pet/Ct; Standardized uptake value; Imaging modalities; Sarcoma
AB The effective management of patients with sarcomas requires accurate diagnosis and staging. Imaging, such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) are the most freqently used methods for the detection of the lesion location, size, morphology and structural changes to adjacent tissues; however, these modalities provide little information about tumour biology. MRI is a robust and useful modality in tumour staging of sarcomas, however metabolic-fluorodeoxyglucose positron emission tomography/ computer tomography (18F–FDG PET/CT) provides greater accuracy to overall staging in combination with MRI [1]. The advantages of 18F–FDG PET/CT method compared with CT and MRI is that it provides a whole body imaging, maps the viability of the tumour or themetabolic activity of the tissue. Additionally, PET detects the most agressive part of the tumour, demonstrates the biological behaviour of the tumour and therefore has a predictive value. Little data ara available on the role of 18F–FDG PET/CT in the management of sarcomas. The present manuscript aims to provide a review of the major indications of 18F–FDG PET/CT for diagnosis, staging, restaging and monitoring response to therapy and to compare its usefulness with the conventional imaging modalities in the management of patients with sarcomas.
C1 [Nemeth, Zsuzsanna] Szent Margit Hospital, V. Department of Internal Medicine - OncologyBudapest, Hungary.
[Boer, Katalin] Szent Margit Hospital, V. Department of Internal Medicine - OncologyBudapest, Hungary.
[Borbely, Katalin] National Institute of Oncology, PET/CT Outpatient DepartmentBudapest, Hungary.
RP Nemeth, Zs (reprint author), Szent Margit Hospital, V. Department of Internal Medicine - Oncology, Budapest, Hungary.
EM zsnemethzsuzsanna@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 131
EP 136
DI 10.1007/s12253-017-0325-0
PG 6
ER
PT J
AU CJ, P
HV, E
Vijayakurup, V
Menon, RG
Nair, S
Gopala, S
AF CJ, Padmakrishnan
HV, Easwer
Vijayakurup, Vinod
Menon, R Girish
Nair, Suresh
Gopala, Srinivas
TI High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Autophagy; LC3; Autophagic flux; p62; Beclin 1
ID Glioma; Autophagy; LC3; Autophagic flux; p62; Beclin 1
AB Recent studies suggest the role of autophagy, an evolutionarily conserved catabolic process, in determining the response of gliomas to treatment either positively or negatively. The study attempts to characterize autophagy in low and highgrade glioma by investigating the autophagic flux and clinical significance of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We evaluated the expression of autophagic markers in resected specimens of low-grade glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and Western blotting. Our results show that expression of autophagy proteins were more prominent in HGG than in LGG. Increased level of autophagic proteins in HGG can be due to an increased rate of autophagy or can be because of blockage in the final degradation step of autophagy (defective autophagy). To distinguish these possibilities, the autophagic flux assaywhich helps to determine the rate of degradation/synthesis of autophagic proteins (LC3-II and p62) over a period of time by blocking the final degradation step of autophagy using bafilomycin A1 was used. The assessment of autophagic flux in ex vivo culture of primary glioma cells revealed for the first time increased turnover of autophagy in high grade compared to low grade-glioma. Though autophagic markers were reduced in LGG, functionally autophagy was non defective in both grades of glioma. We then investigated whether autophagy in gliomas is regulated by nutrient sensing pathways including mTOR and promote cell survival by providing an alternate energy source in response to metabolic stress. The results depicted that the role of autophagy during stress varies with tissue and has a negative correlation with mTOR substrate phosphorylation.We also evaluated the expression of LC3 and beclin 1 with progression free survival (PFS) using Kaplan-Meier survival analysis and have found that patients with low LC3/beclin 1 expression had better PFS than those with high expression of LC3/beclin 1 in their tumors. Together, we provide evidence that autophagy is non-defective in glioma and also show that high LC3/beclin 1 expression correlates with poor PFS in both LGG and HGG.
C1 [CJ, Padmakrishnan] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Biochemistry, 695011 Thiruvananthapuram, Kerala, India.
[HV, Easwer] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurosurgery, 695011 Thiruvananthapuram, Kerala, India.
[Vijayakurup, Vinod] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Biochemistry, 695011 Thiruvananthapuram, Kerala, India.
[Menon, R Girish] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurosurgery, 695011 Thiruvananthapuram, Kerala, India.
[Nair, Suresh] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurosurgery, 695011 Thiruvananthapuram, Kerala, India.
[Gopala, Srinivas] Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Biochemistry, 695011 Thiruvananthapuram, Kerala, India.
RP Gopala, S (reprint author), Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Biochemistry, 695011 Thiruvananthapuram, India.
EM srinivasg@sctimst.ac.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 137
EP 148
DI 10.1007/s12253-017-0310-7
PG 12
ER
PT J
AU Maraz, A
Csejtei, A
Kocsis, J
Szucs, M
Kahan, Zs
Bodoky, Gy
Dank, M
Mangel, L
Revesz, J
Varga, Z
Geczi, L
AF Maraz, Aniko
Csejtei, Andras
Kocsis, Judit
Szucs, Miklos
Kahan, Zsuzsanna
Bodoky, Gyorgy
Dank, Magdolna
Mangel, Laszlo
Revesz, Janos
Varga, Zoltan
Geczi, Lajos
TI Assessment of the Role of Everolimus Therapy in Patients with Renal Cell Carcinoma Based on Daily Routine and Recent Research Results
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastatic kidney cancer; mTOR inhibitor; Everolimus; Anemia; ECOG; RCC
ID Metastatic kidney cancer; mTOR inhibitor; Everolimus; Anemia; ECOG; RCC
AB Everolimus is indicated for adults with metastatic renal cell carcinoma (mRCC) after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitors (TKI). Currently, the therapeutic applicability of EVE has been changing. Multicenter evaluation of efficacy and safety of everolimus in daily routine and definition of patient characteristics with favorable outcome. Data of 165 patients from 9 oncology institutes in Hungary were analyzed retrospectively. Everolimus therapy was used after one TKI in 10 mg starting dose. Physical and laboratory examinations and imaging tests were performed monthly and every 3 months, respectively. Median progression-free survival (PFS) was 5.4 months.Median overall survival (OS) was 16.2 months. PFS and OS results were more favorable in patients with ECOG 0–1 (pPFS = 0.033, pOS = 0.008) and after >9 months of TKI therapy (pPFS = 0.019, pOS = 0.045). Survival was longer in nonanemic patients with ECOG 0–1 than in anemic patients with ECOG 2–3, 30.9 and 7.7 months, respectively (p = 0.029). Dose reduction and treatment delay was required in 6.2% and 8.9% of patients, respectively. Common adverse events were exanthema, edema, stomatitis, anemia, and abnormal kidney functions and glucose levels. Results of this study show that everolimus is safe and efficacious in a real-world setting. Everyday practice showed that nonanemic patients with good performance status receiving TKI therapy for >9 months are favorable candidates for this treatment. Despite the efficiency of novel, registered drugs, everolimus still plays an important role during and after second-line therapy for mRCC when availability of modern remedies is limited.
C1 [Maraz, Aniko] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Csejtei, Andras] Vas County Markusovszky Hospital, Markusovszky str. 5Szombathely, Hungary.
[Kocsis, Judit] University of Debrecen, Department of Oncology, Nagyerdei krt. 98Debrecen, Hungary.
[Szucs, Miklos] Semmelweis University, Department of Urology, Ulloi str. 78/bBudapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Bodoky, Gyorgy] Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, Albert Florian str. 5-7Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, 1st Department of Internal Medicine, Tomo str. 25-29Budapest, Hungary.
[Mangel, Laszlo] University of Pecs, Department of Oncology, Edesanyak 17Pecs, Hungary.
[Revesz, Janos] Borsod County Hospital and University Academic Hospital, Institute of Radiotherapy and Clinical Oncology, Szentpeteri Kapu 72-76Miskolc, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
[Geczi, Lajos] National Institute of Oncology, Department of Chemotherapy and Clinicopharmacology, Rath Gyorgy str. 7-9Budapest, Hungary.
RP Maraz, A (reprint author), University of Szeged, Department of Oncotherapy, 6720 Szeged, Hungary.
EM dr.aniko.maraz@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 149
EP 156
DI 10.1007/s12253-017-0317-0
PG 8
ER
PT J
AU Li, D
Yang, Z
Liu, Z
Zou, Q
Yuan, Y
AF Li, Daiqiang
Yang, Zhulin
Liu, Ziru
Zou, Qiong
Yuan, Yuan
TI DDR2 and IFITM1 Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gallbladder; Squamous cell carcinoma; Adenosquamous carcinomas; DDR2; IFITM1; Immunohistochemistry
ID Gallbladder; Squamous cell carcinoma; Adenosquamous carcinomas; DDR2; IFITM1; Immunohistochemistry
AB This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2 was significantly higher in SC/ASC patients with large tumor sizes than patients with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1 expressions was significantly higher in AC patients with high TNM stages that didn’t receive resection surgery compared to patients with low TNM stages that did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1 was significantly higher in AC patients with lymph node metastasis and invasion than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and IFITM1 expression was closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC.
C1 [Li, Daiqiang] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
[Yang, Zhulin] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan, China.
[Liu, Ziru] Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, Hunan, China.
[Zou, Qiong] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
[Yuan, Yuan] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, Hunan, China.
RP Yang, Z (reprint author), Central South University, The Second Xiangya Hospital, Department of General Surgery, 410011 Changsha, China.
EM yangzhulin8@sina.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 157
EP 167
DI 10.1007/s12253-017-0314-3
PG 11
ER
PT J
AU Darvasi, O
Szabo, MP
Nemeth, K
Szabo, K
Spisak, S
Liko, I
Czirjak, S
Racz, K
Igaz, P
Patocs, A
Butz, H
AF Darvasi, Otto
Szabo, Marton Peter
Nemeth, Kinga
Szabo, Katalin
Spisak, Sandor
Liko, Istvan
Czirjak, Sandor
Racz, Karoly
Igaz, Peter
Patocs, Attila
Butz, Henriett
TI Limitations of high throughput methods for miRNA expression profiles in non-functioning pituitary adenomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miRNA; miRNA profiling; Non-functioning pituitary adenoma
ID miRNA; miRNA profiling; Non-functioning pituitary adenoma
AB Microarray, RT-qPCR based arrays and nextgeneration- sequencing (NGS) are available high-throughput methods for miRNA profiling (miRNome). Analytical and biological performance of these methods were tested in identification of biologically relevant miRNAs in non-functioning pituitary adenomas (NFPA). miRNome of 4 normal pituitary (NP) and 8 NFPA samples was determined by these platforms and expression of 21 individual miRNAs was measured on 30 (20 NFPA and 10 NP) independent samples. Complex bioinformatics was used. 132 and 137 miRNAs were detected by all three platforms in NP and NFPA, respectively, of which 25 were differentially expressed (fold change > 2). The strongest correlation was observed between microarray and TaqManarray, while the data obtained by NGS were the most discordant despite of various bioinformatics settings. As a technical validation we measured the expression of 21 selected miRNAs by individual RT-qPCR and we were able to validate 35.1%, 76.2%and 71.4%of the miRNAs revealed by SOLiD, TLDA and microarray result, respectively. We performed biological validation using an extended number of samples (20 NFPAs and 8 NPs). Technical and biological validation showed high correlation (p < 0.001; R = 0.96). Pathway and network analysis revealed several common pathways but no pathway showed the same activation score. Using the 25 platform-independent miRNAs developmental pathways were the top functional categories relevant for NFPA genesis. The difference among high-throughput platforms is of great importance and selection of screening method can influence experimental results. Validation by another platform is essential in order to avoid or to minimalize the platform specific errors.
C1 [Darvasi, Otto] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Szabo, Marton Peter] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Nemeth, Kinga] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Szabo, Katalin] Semmelweis University, 2nd Department of Internal MedicineBudapest, Hungary.
[Spisak, Sandor] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Liko, Istvan] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Czirjak, Sandor] National Institute of NeurosurgeryBudapest, Hungary.
[Racz, Karoly] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Igaz, Peter] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Patocs, Attila] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Butz, Henriett] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
RP Butz, H (reprint author), Hungarian Academy of Sciences, Molecular Medicine Research Group, Budapest, Hungary.
EM butz.henriett@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 169
EP 182
DI 10.1007/s12253-017-0330-3
PG 14
ER
PT J
AU Jain, D
Tikku, G
Bhadana, P
Dravid, Ch
Grover, KR
AF Jain, Dhruv
Tikku, Gargi
Bhadana, Pallavi
Dravid, Chandrashekhar
Grover, Kumar Rajesh
TI The Impact of Peritumoral Retraction Clefting & Intratumoral Eosinophils on Overall Survival in Oral Squamous Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoma; Squamous cell; Oral cavity; Overall survival; Tumor-associated tissue eosinophilia; Retraction clefting
ID Carcinoma; Squamous cell; Oral cavity; Overall survival; Tumor-associated tissue eosinophilia; Retraction clefting
AB This retrospective study aimed to investigate the impact of peritumoral retraction clefts (RC) and tumorassociated tissue eosinophilia (TATE) as predictors of overall survival (OS) in oral squamous cell carcinoma (OSCC) patients. Their relationships with tumor-factors were also examined. Eighty-seven OSCC cases (pTNM: I + II/III + IV; 32/ 55), post-curative surgery, comprised the study cohort. Three observers independently estimated the percent RC semiquantitatively in the selected tumor sections. Additionally, stromal eosinophils were counted in ten consecutive highpower fields of intratumoral and peritumoral regions to evaluate the corresponding TATE. The percent RC ranged between 0% -90% (Mean ± SD: 16 ± 24%; Median: 5%). The stromal eosinophils were greater in peritumoral as compared to intratumoral region. The events of death and tumor recurrence were reached in 16 (18.4%) and 36 (41%) cases respectively. The 3-years OS was 69% [Median OS: 1880 days; Mean follow up: 471(Range; 36–1880) days]. Increased percent RC exhibited relationship with pathologic stage (pTNM III&IV), primary tumor (pT III&IV), tumor depth > 4 mmand categorical tumor recurrence. Additionally, peritumoral eosinophilic infiltrates increased with increasing tumor depths and muscle invasion. Kaplan-Meier curves revealed significantly reduced OS in OSCC cases exhibiting: increased percent RC (>2.5%), mild -moderate/absent intratumoral TATE (versus intense TATE) or categorical tumor recurrence. In subsequent multivariate tests, all the three variables retained significance. Additionally, intraclass correlation coefficient demonstrated acceptable internal consistency for the observers who estimated percent RC. In conclusion, RC and intratumoral TATE proved to be independent predictors of OS in our OSCC cohort. Additionally, increased percent RC pointed towards aggressive tumor behaviour.
C1 [Jain, Dhruv] Delhi State Cancer Institute, Department of Oncopathology, Dilshad Garden, 110095 Delhi, India.
[Tikku, Gargi] Delhi State Cancer Institute, Department of Oncopathology, Dilshad Garden, 110095 Delhi, India.
[Bhadana, Pallavi] Delhi State Cancer Institute, Department of Oncopathology, Dilshad Garden, 110095 Delhi, India.
[Dravid, Chandrashekhar] Delhi State Cancer Institute, Department of Surgical Oncology, 110095 Delhi, India.
[Grover, Kumar Rajesh] Delhi State Cancer Institute, Department of Clinical Oncology, 110095 Delhi, India.
RP Jain, D (reprint author), Delhi State Cancer Institute, Department of Oncopathology, 110095 Delhi, India.
EM drdhruv_jain@yahoo.co.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 183
EP 189
DI 10.1007/s12253-017-0328-x
PG 7
ER
PT J
AU Afsharpad, M
Nowroozi, RM
Mobasheri, BM
Ayati, M
Nekoohesh, L
Saffari, M
Zendehdel, K
Modarressi, HM
AF Afsharpad, Mandana
Nowroozi, Reza Mohammad
Mobasheri, Beigom Maryam
Ayati, Mohsen
Nekoohesh, Leila
Saffari, Mojtaba
Zendehdel, Kazem
Modarressi, Hossein Mohammad
TI Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional Cell Carcinoma of Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer testis antigen; Clinical markers; Transitional cell carcinoma; Urinary bladder neoplasms
ID Cancer testis antigen; Clinical markers; Transitional cell carcinoma; Urinary bladder neoplasms
AB To evaluate the diagnostic potential of 23 candidate genes, belonging to a category of tumor-specific antigens known as cancer-testis antigens (CTAs), in transitional cell carcinoma (TCC) patients. The expression of 16 known candidate CTAs and seven testis restricted/selective genes, predominantly expressed in the testis, was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Urinary exfoliated cells (UECs) and cancerous tissues of 73 TCC patients were used as cases, while 25 tumor-free adjacent bladder tissue specimens along with bladder tissue specimens and UECs of five non-TCC individuals were analyzed as controls. Among the known CTAs only MAGEA3, MAGEB4, TSGA10, PIWIL2, OIP5, and ODF4 were expressed specifically in TCC tissues and UEC samples. ACTL7A, AURKC, and CGB2 were testis-restricted/selective genes that indicated specific expression in cases in comparison to controls. MAGEA3, MAGEB4, and ODF4 mRNA was detectable in more than 50% of both TCC tissues, and UEC samples. Slight differences were detected in the mRNA expression pattern of candidate genes between the UEC samples and tumor tissues. Different panels formed by combinations of these genes can show up to 95.9% and 94.5% of positivity in TCC tissues and UEC samples, respectively, suggesting their diagnostic and surveillance potential. Meanwhile the RT-PCR assay of at least MAGEA3, MAGEB4, and ODF4 may be particularly useful for diagnostic and surveillance of TCC in the form of a multi-biomarker panel.
C1 [Afsharpad, Mandana] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Nowroozi, Reza Mohammad] Tehran University of Medical Sciences, Uro-Oncology Research CenterTehran, Iran.
[Mobasheri, Beigom Maryam] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Ayati, Mohsen] Tehran University of Medical Sciences, Uro-Oncology Research CenterTehran, Iran.
[Nekoohesh, Leila] Tehran University of Medical Sciences, School of Advanced Technologies in Medicine, International Campus, Department of Medical BiotechnologyTehran, Iran.
[Saffari, Mojtaba] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Zendehdel, Kazem] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Modarressi, Hossein Mohammad] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
RP Modarressi, HM (reprint author), Tehran University of Medical Sciences, Cancer Institute of Iran, Tehran, Iran.
EM modaresi@tums.ac.ir
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 191
EP 199
DI 10.1007/s12253-017-0313-4
PG 9
ER
PT J
AU Zejun, D
Kun, Y
Dehong, L
Xueling, Q
AF Zejun, Duan
Kun, Yao
Dehong, Lu
Xueling, Qi
TI Proximal-Type Epithelioid Sarcoma in Skull Base: a Pathological Diagnosis Challenge with Other Intracranial Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Proximal type epithelioid sarcoma; Middle cranial fossa; Skull base; Atypical teratoid/rhabdoid tumour
ID Proximal type epithelioid sarcoma; Middle cranial fossa; Skull base; Atypical teratoid/rhabdoid tumour
AB Proximal-type ES (PES) is a rare and aggressive sarcoma originated from soft tissues with uncertain differentiation. It mainly affects middle-aged patients and often locates in proximal extremity and deep-seated tissues. Only one case of PES located in the skull base has been reported to date. Herein, we report two cases of PES occurred in the middle cranial fossa in two middle-aged Chinese women. Microscopically, the tumors were consisted of epithelial-like cells with or without rhabdoid cells. And frequent mitotic activity and coagulation necrosis were present. Immunohistochemically, tumor cells in the two cases were positive for vimentin, AE1/AE3, epithelial membrane antigen (EMA), CD34, and synaptophysin. A few number of tumor cells expressed CD56. They were completely negative for integrase interactor-1 (INI1). Besides, TP53 positive cells were observed (>50%) in the two cases. The MIB-1 proliferation index was high up to 50–70%. Fluorescence in situ hybridization showed the monoallelic deletions of INI1. Intracranial PES is needed to identify with other mimic tumors, especially rhabdoid meningioma, epithelioid MPNST and adult AT/RT. The prognosis of the two patients was very poor. They died respectively less than a month and half a month after surgery. Tumor grew rapidly and was easy to infiltrate into the surrounding tissues. It may suggest that the prognosis of PES occurred at the base of skull was worse than in other sites.
C1 [Zejun, Duan] Capital Medical University, San Bo Brain Hospital, Department of PathologyBeijing, China.
[Kun, Yao] Capital Medical University, San Bo Brain Hospital, Department of Pathology, Haidian DistrictBeijing, China.
[Dehong, Lu] Capital Medical University, San Bo Brain Hospital, Department of Pathology, Haidian DistrictBeijing, China.
[Xueling, Qi] Capital Medical University, San Bo Brain Hospital, Department of PathologyBeijing, China.
RP Xueling, Q (reprint author), Capital Medical University, San Bo Brain Hospital, Department of Pathology, Beijing, China.
EM xszqxl169@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 201
EP 208
DI 10.1007/s12253-017-0318-z
PG 8
ER
PT J
AU Seyedin, NS
Mitchell, LD
Mott, LS
Russo, K
Tracy, RCh
Snow, NA
Parkhurst, RJ
Smith, CM
Buatti, MJ
Watkins, MJ
AF Seyedin, N Steven
Mitchell, L Darrion
Mott, L Sarah
Russo, J. Kyle
Tracy, R Chad
Snow, N Anthony
Parkhurst, R Jessica
Smith, C Mark
Buatti, M John
Watkins, M John
TI Is More Always Better? An Assessment of the Impact of Lymph Node Yield on Outcome for Clinically Localized Prostate Cancer with Low/Intermediate Risk Pathology (pT2-3a/pN0) Managed with Prostatectomy Alone
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radical prostatectomy; Lymph node dissection; Localized prostate cancer; Biochemical relapse free survival
ID Radical prostatectomy; Lymph node dissection; Localized prostate cancer; Biochemical relapse free survival
AB The clinical impact of lymph node dissection extent remains undetermined in the contemporary setting, as reflected in care pattern variations. Despite some series demonstrating a direct relationship between number of lymph nodes identified and detection of nodal involvement, the correlation between lymph node yield and disease control or survival outcomes remains unclear. Patients with clinically localized prostate cancer, pre-RP PSA <30, and pT2-3a/N0 disease at RP were retrospectively identified from two databases for inclusion. Those who received pre- or post-RP radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences between subsets. From 2002 to 2010, 667 eligible patients were identified. The median age was 61 yrs. (range, 43–76), with median PSA 5.6 ng/dL (0.9–28.0). At RP, most patients had pT2c (64%) disease with Gleason Score (GS) ≤6 (43%) or 7 (48%); 218 (33%) patients had positive margins (M+). At median clinical and PSA follow-up of 96 and 87 months, respectively, 146 patients (22%) experienced PSA failure with an estimated bRFS of 81%/76% at 5/8 years. For patients who underwent LND, univariable analysis identified PSA (at diagnosis), higher GS (≥7, at biopsy or RP), intermediate/high risk stratification, M+ as adversely associated with bRFS (all p < 0.01). A higher number of LNs excised was not associated with improved bRFS for the entire cohort (HR = 0.97, p = 0.27), nor for any clinical risk stratum, biopsy GS, or RP GS subgroup. This study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2- 3a/pN0 prostate cancer managed with RP alone, either in the entire population or with substratification by clinical risk stratum or GS.
C1 [Seyedin, N Steven] University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 200 Hawkins Drive, 52242 Iowa City, IA, USA.
[Mitchell, L Darrion] The Ohio State University, Department of Radiation OncologyColumbus, OH, USA.
[Mott, L Sarah] University of Iowa, Holden Comprehensive Cancer CenterIowa City, IA, USA.
[Russo, J. Kyle] Bismarck Cancer CenterBismarck, ND, USA.
[Tracy, R Chad] University of Iowa, Department of UrologyIowa City, IA, USA.
[Snow, N Anthony] University of Iowa, Department of PathologyIowa City, IA, USA.
[Parkhurst, R Jessica] University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 200 Hawkins Drive, 52242 Iowa City, IA, USA.
[Smith, C Mark] University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 200 Hawkins Drive, 52242 Iowa City, IA, USA.
[Buatti, M John] University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 200 Hawkins Drive, 52242 Iowa City, IA, USA.
[Watkins, M John] University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 200 Hawkins Drive, 52242 Iowa City, IA, USA.
RP Watkins, MJ (reprint author), University of Iowa, Carver School of Medicine, Department of Radiation Oncology, 52242 Iowa City, USA.
EM john.m.watkins.md@hotmail.com
CR Ferlay JSI, Ervik M, Dikshit R, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No 11 [Internet] Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 01/11/2017
Lu-Yao GL, Greenberg ER, 1994, Changes in prostate cancer incidence and treatment in USA. Lancet 343:251–254
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 209
EP 215
DI 10.1007/s12253-017-0349-5
PG 7
ER
PT J
AU Felkai, L
Banusz, R
Kovalszky, I
Sapi, Z
Garami, M
Papp, G
Karaszi, K
Varga, E
Csoka, M
AF Felkai, Luca
Banusz, Rita
Kovalszky, Ilona
Sapi, Zoltan
Garami, Miklos
Papp, Gergo
Karaszi, Katalin
Varga, Edit
Csoka, Monika
TI The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALK; Crizotinib; Soft tissue sarcoma; Neuroblastoma; Inflammatory myofibroblastic tumor
ID ALK; Crizotinib; Soft tissue sarcoma; Neuroblastoma; Inflammatory myofibroblastic tumor
AB Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7%vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.
C1 [Felkai, Luca] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9, H-1094 Budapest, Hungary.
[Banusz, Rita] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9, H-1094 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Garami, Miklos] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9, H-1094 Budapest, Hungary.
[Papp, Gergo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Karaszi, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Varga, Edit] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9, H-1094 Budapest, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of Pediatrics, Tuzolto u. 7-9, H-1094 Budapest, Hungary.
RP Csoka, M (reprint author), Semmelweis University, 2nd Department of Pediatrics, H-1094 Budapest, Hungary.
EM dr.csoka.monika@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 217
EP 224
DI 10.1007/s12253-017-0332-1
PG 8
ER
PT J
AU Mitrakas, L
Gravas, S
Papandreou, Ch
Koukoulis, G
Karasavvidou, F
Dimakopoulos, G
Weingartner, K
Karatzas, A
Zachos, I
Tzortzis, V
AF Mitrakas, Lampros
Gravas, Stavros
Papandreou, Christos
Koukoulis, Georgios
Karasavvidou, Foteini
Dimakopoulos, Georgios
Weingartner, Karl
Karatzas, Anastasios
Zachos, Ioannis
Tzortzis, Vasilios
TI Primary High-Grade Non-Muscle-Invasive Bladder Cancer: High NFκB Expression in Tumor Specimens Distinguishes Patients Who are at Risk for Disease Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NFκΒ; High-grade; Non-muscle-invasive; Bladder cancer; Progression; BCG
ID NFκΒ; High-grade; Non-muscle-invasive; Bladder cancer; Progression; BCG
AB To investigate the potential prognostic role of NFκB expression in primary high-grade non-muscle-invasive bladder cancer. Patients with primary high-grade non-muscle-invasive bladder cancer who received induction and maintenance BCG therapy were retrospectively included. Recurrence and progression were histologically proven. Intensity and extent of immunochemistry were assessed. The final evaluation of the NFκB staining was done by combining intensity and extent as product and expressing it as low NFκΒ expression or high NFκB expression . Epidemiological, pathological, clinical parameters and NFκB expression were statistically analyzed for recurrence (REC), progression (PR), recurrence-free survival (RFS) and progression-free survival (PFS). NFκB is significantly associated with disease progression (p < 0,001 in univariate analysis and p = 0,001, Odds Ratio = 14,484, 95% Confidence Interval = 3187-65,821 in multivariate analysis), but not with recurrence. The median value of NFκB expression as product is significantly higher for the patients with progression in comparison to patients with recurrence only (p = 0,003) and patients without recurrence or progression (p = 0,001). Patients’ age is significantly associated (p = 0,001 in univariate analysis and p = 0,003, Odds Ratio = 1273, 95% Confidence Interval = 1086–1492 in multivariate analysis) with disease recurrence. High NFκB expression in primary high-grade non-muscle-invasive bladder cancer, treated with postoperative intravesical BCG immunotherapy, could represent an unfavorable prognostic factor.
C1 [Mitrakas, Lampros] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of UrologyLarissa, Greece.
[Gravas, Stavros] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of UrologyLarissa, Greece.
[Papandreou, Christos] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of OncologyLarissa, Greece.
[Koukoulis, Georgios] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Karasavvidou, Foteini] University of Thessaly, Medical School, Department of PathologyLarissa, Greece.
[Dimakopoulos, Georgios] Science and Technology Park of Epirus, Medical StatisticsIoannina, Greece.
[Weingartner, Karl] Akademisches Lehrkrankenhaus der Friedrich-Alexander-Universitat Erlangen-Nurnberg, Sozialstiftung Bamberg-Klinikum am Bruderwald, Klinik fur Urologie und Kinderurologie, Buger Straße 80, 96049 Bamberg, Germany.
[Karatzas, Anastasios] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of UrologyLarissa, Greece.
[Zachos, Ioannis] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of UrologyLarissa, Greece.
[Tzortzis, Vasilios] University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of UrologyLarissa, Greece.
RP Mitrakas, L (reprint author), University Hospital of Larissa, Faculty of Medicine-School of Health Sciences-University of Thessaly, Department of Urology, Larissa, Greece.
EM lamprosmit@gmail.com
CR BabjukM, BohleA, Burger M, Capoun O, CohenD, ComperatEM et al, 2016, EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. , DOI 10.1016/j.eururo.2016.05.041
Sylvester RJ, Brausi MA, KirkelsWJ, HoeltlW, Calais Da Silva F, Powell PH et al, 2010, Long-term efficacy results of EORTC Genito-Urinary Group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guerin, and bacillus Calmette-Guerin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. Eur Urol 57(5):766–773
Soloway M, Khoury S, 2012, Bladder cancer. 2nd edition 2012: ICUD-EAU; 254, 261. EDITIONS 21, Paris, France
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Zachos I, Konstantinopoulos PA, Vandoros GP, Karamouzis MV, Papatsoris AG, Podimatas T et al, 2009, Predictive value of telomerase reverse transcriptase expression in patients with high risk superficial bladder cancer treated with adjuvant BCG immunotherapy. J Cancer Res Clin Oncol 135(9):1169–1175
Saint F, Salomon L, Quintela R, Cicco A, Hoznek A, Abbou CC et al, 2003, Do prognostic parameters of remission versus relapse after bacillus Calmette-Guerin, BCG, immunotherapy exist? Analysis of a quarter century of literature. Eur Urol 43(4):351–360
Ghosh S, May M, Kopp EB, 1998, NFκB and Rel proteins: evolutionary conserved mediators of immune responses. Annu Rev Immunol 16:225–260
Levidou G, Saetta AA, Korkolopoulou P, Papanastasiou P, Gioti K, Pavlopoulos P et al, 2008, Clinical significance of nuclear factor, NF)-Κb levels in urothelial carcinoma of the urinary bladder. Virchows Arch 452(3):295–304
Kang S, Kim YB, Kim MH, Yoon KS, Kim JW, Park NH et al, 2005, Polymorphism in the nuclear factor kappa-B binding promoter region of cyclooxygenase-2 is associated with an increased risk of bladder cancer. J Can Let 217(1):11–16
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SasakiN,Morisaki T, Hashizume K,Yao T, TsuneyoshiM, Noshiro H et al, 2001, Nuclear factor-kappaB p65, RelA, transcription factor is constitutively activated in human gastric carcinoma tissue. Clin Cancer Res 12:4136–4142
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 225
EP 231
DI 10.1007/s12253-017-0340-1
PG 7
ER
PT J
AU Seclaman, E
Narita, D
Anghel, A
Cireap, N
Ilina, R
Sirbu, OI
Marian, C
AF Seclaman, Edward
Narita, Diana
Anghel, Andrei
Cireap, Natalia
Ilina, Razvan
Sirbu, Ovidiu Ioan
Marian, Catalin
TI MicroRNA Expression in Laser Micro-dissected Breast Cancer Tissue Samples – a Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; MicroRNA; Laser capture microdissection (LCM)
ID Breast cancer; MicroRNA; Laser capture microdissection (LCM)
AB Breast cancer continues to represent a significant public health burden despite outstanding research advances regarding the molecular mechanisms of cancer biology, biomarkers for diagnostics and prognostic and therapeutic management of this disease. The studies of micro RNAs in breast cancer have underlined their potential as biomarkers and therapeutic targets; however most of these studies are still done on largely heterogeneous whole breast tissue samples. In this pilot study we have investigated the expression of four micro RNAs (miR-21, 145, 155, 92) known to be involved in breast cancer, in homogenous cell populations collected by laser capture microdissection from breast tissue section slides. Micro RNA expression was assessed by real time PCR, and associations with clinical and pathological characteristics were also explored. Our results have confirmed previous associations of miR-21 expression with poor prognosis characteristics of breast cancers such as high stage, large and highly proliferative tumors. No statistically significant associations were found with the other micro RNAs investigated, possibly due to the small sample size of our study. Our results also suggest that miR-484 could be a suitable endogenous control for data normalization in breast tissues, these results needing further confirmation by future studies. In summary, our pilot study showed the feasibility of detecting micro RNAs expression in homogenous laser captured microdissected invasive breast cancer samples, and confirmed some of the previously reported associations with poor prognostic characteristics of breast tumors.
C1 [Seclaman, Edward] University of Medicine and Pharmacy, Biochemistry Department, Pta Eftimie Murgu Nr. 2, 300041 Timisoara, Romania.
[Narita, Diana] University of Medicine and Pharmacy, Biochemistry Department, Pta Eftimie Murgu Nr. 2, 300041 Timisoara, Romania.
[Anghel, Andrei] University of Medicine and Pharmacy, Biochemistry Department, Pta Eftimie Murgu Nr. 2, 300041 Timisoara, Romania.
[Cireap, Natalia] University of Medicine and Pharmacy, Department of Surgical OncologyTimisoara, Romania.
[Ilina, Razvan] University of Medicine and Pharmacy, Department of Surgical OncologyTimisoara, Romania.
[Sirbu, Ovidiu Ioan] University of Medicine and Pharmacy, Biochemistry Department, Pta Eftimie Murgu Nr. 2, 300041 Timisoara, Romania.
[Marian, Catalin] University of Medicine and Pharmacy, Biochemistry Department, Pta Eftimie Murgu Nr. 2, 300041 Timisoara, Romania.
RP Marian, C (reprint author), University of Medicine and Pharmacy, Biochemistry Department, 300041 Timisoara, Romania.
EM cmarian@umft.ro
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 233
EP 239
DI 10.1007/s12253-017-0343-y
PG 7
ER
PT J
AU Nagyivanyi, K
Budai, B
Kuronya, Zs
Gyergyay, F
Biro, K
Bodrogi, I
Geczi, L
AF Nagyivanyi, Krisztian
Budai, Barna
Kuronya, Zsofia
Gyergyay, Fruzsina
Biro, Krisztina
Bodrogi, Istvan
Geczi, Lajos
TI Outcome of Restarted Sunitinib Treatment in Patients with Metastatic Renal Cell Carcinoma: a Retrospective Trial and Combined Case Reports from Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Drug holiday; Overall survival; Patient’s choice; Progression-free survival; Toxicity
ID Drug holiday; Overall survival; Patient’s choice; Progression-free survival; Toxicity
AB In practice it is still not clear whether a drug holiday in sunitinib (Su) treatment can be safety, without impairing the overall outcome of patients with metastatic renal cell carcinoma (mRCC). The aim was to retrospectively evaluate the outcome in patients who restarted Su after an interruption of ≥3 months and a combined analysis of case studies from literature. From 556 patients treated between January 2006 and March 2016 a group of 38 patients were selected whose treatment was interrupted for other reasons than disease progression. During interruption Su was restarted in case of RECIST-defined progression. The primary objective was the objective response (OR) and progression free survival (PFS) of baseline and restarted therapy. The secondary objective was the overall survival (OS) calculated from the start of baseline treatment. Multivariate survival analysis was also applied. The major causes of interruption were toxicity (39%) and patient’ choice (24%). Median duration of interruption was 7 (range 3–41) months. The OR of baseline and restarted treatment was 63% and 39%, respectively. After a median follow-up of 76 (95% CI 65–79) months the median PFS of baseline and restarted treatment was 21 (18–27) and 14 (10–18) months, respectively. The median OS was 61 (56–80) months. In multivariate analysis the lack of OR of restated treatment was an independent predictor of shorter PFS of restarted Su. According to our findings and also on combined case studies from literature restarted Su can be effective in selected cases of patients who progressed during treatment holiday.
C1 [Nagyivanyi, Krisztian] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Budai, Barna] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Kuronya, Zsofia] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Gyergyay, Fruzsina] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Biro, Krisztina] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Bodrogi, Istvan] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
[Geczi, Lajos] National Institute of Oncology, Rath Gy. u. 7-9, 1122 Budapest, Hungary.
RP Budai, B (reprint author), National Institute of Oncology, 1122 Budapest, Hungary.
EM budai@oncol.hu
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Greef B, Eisen T, 2016, Medical treatment of renal cancer: new horizons. Br J Cancer 115:505–516. , DOI 10.1038/bjc. 2016.230
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 241
EP 247
DI 10.1007/s12253-017-0345-9
PG 7
ER
PT J
AU Kravchick, S
Cherniavsky, E
Verchovsky, G
Peled, R
AF Kravchick, Sergey
Cherniavsky, Eugenia
Verchovsky, Guy
Peled, Ronit
TI Multidetector Computed Tomographic Urography (MDCTU): Its Practical Role in Diagnosis of Upper Tract Urothelial Cancer in Patients 50 years and Older with Different Types of Hematuria
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Upper tract TCC; Computer tomography; Urography; Hematuria; Ureteroscopy
ID Upper tract TCC; Computer tomography; Urography; Hematuria; Ureteroscopy
AB MDCTU is a preferred method for the investigation of malignant lesions in the upper urinary tract. However, to decrease unnecessary radiation exposure the indications for the exam in different groups of patients should be assessed. In this study, we evaluated the role of MDCTU in patients older than 50 years who presented with different types of hematuria. In a retrospective manner, we assessed the radiologic reports of 173 patients ≥50 years who underwent MDCTU as a part of the evaluation for hematuria. To estimate the accuracy of MDCTU in the detection of upper urinary tract urothelial carcinoma (UUTUC) we compared MDCTU findings with the results of ureteroscopy.We also evaluated which factors can predict ureteroscopic confirmation of MDCTU based diagnosis. In this list we also included diabetes mellitus and anticoagulant medications. As a result, 140 (103 males and 37 females) patients met the inclusion criteria. Mean patients' age was 69.7±16.98. Smokers and passive smokers comprised 38.6% and 26.4% of our patients, while 37.8% of our patients suffered from DM and 45% took anticoagulant medications. MDCTU suspected urothelial carcinoma in 17% (n=24) of our patients: UUTUC in eight and bladder urothelial carcinoma (BUC) in 16patients. Ureteroscopy had diagnosed UUTUC (with/without concurrent urothelial carcinoma of the bladder) in 9 patients: 6 with suspicious lesions in MDCTU and 3 additional patients with CIS/small low grade TCC. MDCTU had a sensitivity of 66.7%, specificity - 98.5%, positive predictive value - 75% and negative predictive value - 97.7%. The logistic regression model revealed five strong predictors for UUTUC: positive/atypical cytology, recurrent hematuria, MDCTU signs, age and Warfarin treatment. Finally a source of hematuria was diagnosed in 57% of patients, while MDCTU individual accuracy reached 42%. We found that MDCTU can effectively identify patients in whom further endoscopy is unnecessary. Otherwise, elder patients with positive/atypical cytology and recurrent microscopic hematuria, who have MDCTU signs and take Warfarin, should undergo endoscopic evaluation.
C1 [Kravchick, Sergey] Assaf Harofeh Medical Center, Department of UrologyZrefin, Israel.
[Cherniavsky, Eugenia] Barzilay Medical Center, Department of RadiologyAshkelon, Israel.
[Verchovsky, Guy] Assaf Harofeh Medical Center, Department of UrologyZrefin, Israel.
[Peled, Ronit] Ben Gurion University, Epidemiology and StatisticsBeer-Sheva, Israel.
RP Kravchick, S (reprint author), Assaf Harofeh Medical Center, Department of Urology, Zrefin, Israel.
EM kravchick.sergey@gmail.com
CR Munoz JJ, Ellison LM, 2000, Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 164(5): 1523–1525
Roupreˆt M, Babjuk M, Comperat E et al, 2013, European guidelines on upper tract urothelial carcinomas: 2013 update. Eur Urol 63:1059–1071
Babjuk M, Burger M, Zigeuner R et al, 2013, EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64:639–653
Siegel R, Naishadham D, Jemal A, 2012, Cancer statistics, 2012. CA Cancer J Clin 62:10–29
Roupreˆt M, Babjuk M, Comperat E, Zigeuner R et al, 2015, European Association of Urology guidelines on upper urinary tract urothelial cell carcinoma: 2015 update. Eur Urol 68:868–879
Azemar MD, Comperat E, Richard F, Cussenot O, Roupret M, 2011, Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance. Urol Oncol 29(2):130–136
Raman JD, Ng CK, Scherr DS et al, 2010, Impact of tumor location on prognosis for patients with upper tract urothelial carcinomamanaged by radical Nephroureterectony. Eur Urol 57(6):1072–1079
LiWM, Shen JT, Li CC et al, 2010, Oncologic outcomes following three different Aproaches to the distal ureter and bladder cuff in Nephroureterectomy for primary upper urinary tract urothelial carcinoma. Eur Urol 57(6):963–969
Margulis V, Shariat SF, Matin SF et al, 2009, Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer 115(6):1224–1233
Van Der Molen AJ, Cowan NC, Mueller-Lisse UG et al, 2008, CT urography: definition, indications and techniques. A guideline for clinical practice. Eur Radiol 18(1):4–17
Wang LJ, Wong YC, Chuang CK et al, 2009, Diagnostic accuracy of transitional cell carcinoma on multidetector computerized tomography urography in patients with gross hematuria. J Urol 181(2):524–531
Wang LJ,Wong YC, Huang CC et al, 2010)Multidetector computerized tomography urography ismore accurate than excretory urography for diagnosing transitional cell carcinoma of the upper tract in adults with hematuria. J Urol 183(1):48–55
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Loo RK, Lieberman SF, Slezak JM et al, 2013, Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria. Mayo Clin Proc 88(2):129–138
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Lisanti CJ1, Toffoli TJ, Stringer MT, DeWitt RM, Schwope RB, 2014, CTevaluation of the upper urinary tract in adults younger than 50 years with asymptomatic microscopic hematuria: is IV contrast enhancement needed? AJR Am J Roentgenol 203(3):615–619
Raman SP, Horton KM, Fishman EK, 2012, Transitional cell carcinoma of the upper urinary tract: optimizing image interpretation with 3D reconstructions. Abdom Imaging 37:1129–1140
Johnson PT, Horton KM, Fishman EK, 2010, Optimizing detectability of renal pathology with MDCT: protocols, pearls, and pitfalls. AJR 194:1001–1012
Woolcott CG1, Maskarinec G, Haiman CA, Henderson BE, Kolonel LN, 2011, Diabetes and urothelial cancer risk: the multiethnic cohort study. Cancer Epidemiol 35(6):551–554
Jung H, Gleason JM, Loo RK et al, 2011, Association of hematuria on microscopic urinalysis and risk of urinary tract cancer. J Urol 185(5):1698–1703
Munoz JJ, Ellison LM, 2000, Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 164: 1523–1525
van Osch FH, Jochems SH, van Schooten FJ, Bryan RT, Zeegers MP, 2016, Significant role of lifetime cigarette smoking in worsening bladder cancer and upper tract urothelial carcinoma prognosis: a meta-analysis. J Urol 195(4):872–879
Caoili EM, Cohan RH, Inampudi P et al, 2005, MDCT urography of upper tract urothelial neoplasms. AJR 184:1873–1881
Xu AD, Ng CS, Kamat A, Grossman HB, Dinney C, Sandler CM, 2010, Significance of upper urinary tract urothelial thickening and filling defect seen onMDCT urography in patients with a history of urothelial neoplasms. AJR 195:959–965
Browne RF, Meehan CP, Colville J, Power R, Torreggiani WC, 2005, Transitional cell carcinoma of the upper urinary tract: spectrum of imaging findings. Radiographics 25:1609–1627
Xu AD1, Ng CS, Kamat A, Grossman HB, Dinney C, Sandler CM, 2010, Significance of upper urinary tract urothelial thickening and filling defect seen onMDCT urography in patients with a history of urothelial neoplasms. AJR Am J Roentgenol 195(4):959–965
Khadra MH, Pickard RS, Charlton M et al, 2000, A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol 163(2):524–527
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 249
EP 254
DI 10.1007/s12253-017-0333-0
PG 6
ER
PT J
AU Eide, N
Faye, SR
Hoifodt, KH
Sandvik, L
Qvale, AG
Faber, R
Jebsen, P
Kvalheim, G
Fodstad,
AF Eide, Nils
Faye, S Ragnar
Hoifodt, K Hanne
Sandvik, Leiv
Qvale, A Geir
Faber, Rowan
Jebsen, Peter
Kvalheim, Gunnar
Fodstad, Oystein
TI The Results of Stricter Inclusion Criteria in an Immunomagnetic Detection Study of Micrometastatic Cells in Bone Marrow of Uveal Melanoma Patients - Relevance for Dormancy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Micrometastasis in bone marrow; Uveal melanoma; Exclusion criteria; Immunomagnetic detection; Survival; Tumour dormancy
ID Micrometastasis in bone marrow; Uveal melanoma; Exclusion criteria; Immunomagnetic detection; Survival; Tumour dormancy
AB Approximately 50% of uveal melanoma patients develop metastases. We want to evaluate the effect of stricter criteria on our data from our previous study correlating survival and bone marrow (BM) micrometastasis results using our immunomagnetic separation (IMS) method. Mononuclear cell fractions (MNC) isolated from BM were examined for tumour cells and the patients were classified as BM positive (BM+) or BM negative (BM-). The study originally included 328 consecutive patients with uveal melanoma from 1997 to 2006. The cohort was limited to 217 patients when we introduced cyto- or histopathological verification of melanoma cells in the patient as a main new criterion for inclusion. Tumour cells were found in BM-samples in 38.7% (95% CI, 32–45) at enrolment. Until the latest workup 43.8% (95% CI, 38–50) of patients had developed melanoma metastases. After a minimum follow-up time of 8.5 years, 60.4% (95% CI, 54–66) of patients had died. The causes were: melanoma metastases 69.5%, another type of cancer 5.4% and non-cancerous causes 19.5%. Overall median survival was shorter for the BM- patients (11.3 years) (95% CI, 10–12) compared to the BM+ (16.5 years) (95% CI, 12–14), p = 0.04, log rank test. All-cause mortality and specific melanoma mortality estimated after 12 year follow-up showed a highly significant difference comparing BM- and BM+, p = 0.010 and p = 0,017, respectively. IMS yields a high fraction of BM+ samples due to micrometastasis at diagnosis and these cells appear to have a positive prognostic impact strengthening our previous report. The late recurrences support the concept of tumour dormancy.
C1 [Eide, Nils] Oslo University Hospital HF, Department of Ophthalmology, Nydalen, 0424 Oslo, Norway.
[Faye, S Ragnar] Oslo University Hospital HF, Department of DermatologyOslo, Norway.
[Hoifodt, K Hanne] Oslo University Hospital HF, Department of Tumor BiologyOslo, Norway.
[Sandvik, Leiv] Oslo University Hospital HF, Department of StatisticsOslo, Norway.
[Qvale, A Geir] Oslo University Hospital HF, Department of Ophthalmology, Nydalen, 0424 Oslo, Norway.
[Faber, Rowan] Oslo University Hospital HF, Department of Ophthalmology, Nydalen, 0424 Oslo, Norway.
[Jebsen, Peter] Oslo University Hospital HF, Division of PathologyOslo, Norway.
[Kvalheim, Gunnar] Oslo University Hospital HF, Department of OncologyOslo, Norway.
[Fodstad, Oystein] Oslo University Hospital HF, Department of Tumor BiologyOslo, Norway.
RP Eide, N (reprint author), Oslo University Hospital HF, Department of Ophthalmology, 0424 Oslo, Norway.
EM uxeidn@ous-hf.no;nils.andreas.eide@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 255
EP 262
DI 10.1007/s12253-017-0355-7
PG 8
ER
PT J
AU Schroeder, CA
Xiao, H
Zhu, Z
Li, Q
Bai, Q
Wakefield, RM
Mann, DJ
Fang, Y
AF Schroeder, C Andrew
Xiao, Huaping
Zhu, Ziwen
Li, Qing
Bai, Qian
Wakefield, R Mark
Mann, D Jeffrey
Fang, Yujiang
TI A Potential Role for Green Tea as a Radiation Sensitizer for Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Green tea; Prostate cancer; Radiation therapy
ID Green tea; Prostate cancer; Radiation therapy
AB Prostate cancer (PCa) is the most common noncutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RTPCR/ IHC were used to investigate the mechanisms.We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/ GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the antiproliferative effect of RT/GT-correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.
C1 [Schroeder, C Andrew] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Xiao, Huaping] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Li, Qing] The Affiliated Hospital of Xiangnan UniversityChenzhou, Hunan, China.
[Bai, Qian] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Wakefield, R Mark] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Mann, D Jeffrey] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, IA, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 263
EP 268
DI 10.1007/s12253-017-0358-4
PG 6
ER
PT J
AU Martinez-Useros, J
Li, W
Georgiev-Hristov, T
Fernandez-Acenero, JM
Borrero-Palacios, A
Perez, N
Celdran, A
Garcia-Foncillas, J
AF Martinez-Useros, Javier
Li, Weiyao
Georgiev-Hristov, Tihomir
Fernandez-Acenero, J Maria
Borrero-Palacios, Aurea
Perez, Nuria
Celdran, Angel
Garcia-Foncillas, Jesus
TI Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic ductal adenocarcinoma; PDAC; NRAS; KRAS; TGCA; Biomarker; Progression-free survival; Overall survival; Grade of differentiation
ID Pancreatic ductal adenocarcinoma; PDAC; NRAS; KRAS; TGCA; Biomarker; Progression-free survival; Overall survival; Grade of differentiation
AB Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its incidence is rising worldwide. Although survival can be improved by surgical resection, when detected at an early stage, this type of cancer is usually asymptomatic, and disease becomes only apparent after metastasis. Adjuvant treatment does not improve survival, thus after surgery there is a lack of predictive and prognosis biomarkers to predict treatment response and survival. The mitogen-activated protein-kinase and phosphoinositide 3- kinase signalling pathways play a crucial role in cancer development and progression. Especially, activated RAS proteins promote cell proliferation through constitutive stimulation of the downstream effectors RAF-MEK-ERK and PI3K-AKT. Mutational status of NRAS is required in several types of cancer like colorectal or cutaneous melanoma. However, mutations in this gene are very scarce in PDAC patients, and NRAS determination is not usually performed in clinical practice for this kind of tumor. In this study, we analyse the association between NRAS protein expression and progression-free survival and overall survival of an homogenous cohort of pancreatic ductal adenocarcinoma patients from a single-centre. Interestingly, we found that patients with high expression not only showed longer progression-free survival than those patients with low expression (22 versus 9 months, respectively) (P = 0.013), but also longer overall survival (43 versus 19 months, respectively) (P = 0.020). These results confirm NRAS expression could be used to differentiate patients according to their prognosis. Proportional hazard model revealed NRAS expression together with grade of differentiation as pathological variables to predict patient’s outcome.
C1 [Martinez-Useros, Javier] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology Division, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Li, Weiyao] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology Division, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Georgiev-Hristov, Tihomir] University Hospital Fundacion Jimenez Diaz, Health Research Institute FJD-UAM, Department of Surgery, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Fernandez-Acenero, J Maria] Hospital Clinico San Carlos, Department of Surgical Pathology, C/ Profesor Martin Lagos, 28040 Madrid, Spain.
[Borrero-Palacios, Aurea] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology Division, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Perez, Nuria] University Hospital Fundacion Jimenez Diaz, Department of Pathology, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Celdran, Angel] University Hospital Fundacion Jimenez Diaz, Health Research Institute FJD-UAM, Department of Surgery, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
[Garcia-Foncillas, Jesus] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology Division, Av. Reyes Catolicos 2, 28040 Madrid, Spain.
RP Garcia-Foncillas, J (reprint author), University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology Division, 28040 Madrid, Spain.
EM jesus.garciafoncillas@oncohealth.eu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 269
EP 278
DI 10.1007/s12253-017-0341-0
PG 10
ER
PT J
AU Laszlo, Z
Farkas, R
Schally, VA
Pozsgai, E
Papp, A
Bognar, L
Tornoczki, T
Mangel, L
Bellyei, Sz
AF Laszlo, Zoltan
Farkas, Robert
Schally, V Andrew
Pozsgai, Eva
Papp, Andras
Bognar, Laura
Tornoczki, Tamas
Mangel, Laszlo
Bellyei, Szabolcs
TI Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radiochemotherapy; AKT; Small heat shock protein; Predictiv factors; Esopageal cancer
ID Radiochemotherapy; AKT; Small heat shock protein; Predictiv factors; Esopageal cancer
AB The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3- year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.
C1 [Laszlo, Zoltan] University of Pecs, Department of Oncology, 7624 Pecs, Hungary.
[Farkas, Robert] University of Pecs, Department of Oncology, 7624 Pecs, Hungary.
[Schally, V Andrew] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Pozsgai, Eva] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Papp, Andras] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Bognar, Laura] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Tornoczki, Tamas] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Mangel, Laszlo] University of Pecs, Department of Oncology, 7624 Pecs, Hungary.
[Bellyei, Szabolcs] University of Pecs, Department of Oncology, 7624 Pecs, Hungary.
RP Bellyei, Sz (reprint author), University of Pecs, Department of Oncology, 7624 Pecs, Hungary.
EM bellyeisz@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 279
EP 288
DI 10.1007/s12253-017-0342-z
PG 10
ER
PT J
AU Beardo, P
Cacho, TD
Izquierdo, L
Alcover-Garcia, BJ
Alcaraz, A
Extramiana, J
Mallofre, C
AF Beardo, Pastora
Cacho, Truan David
Izquierdo, Laura
Alcover-Garcia, Bautista Joan
Alcaraz, Antonio
Extramiana, Javier
Mallofre, Carmen
TI Cancer-Specific Survival Stratification Derived from Tumor Expression of Tissue Inhibitor of Metalloproteinase-2 in Non-Metastatic Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Matrix metalloproteinases; Tissue inhibitors of metalloproteinases; Renal cellcarcinoma; Metastasis; Survival
ID Matrix metalloproteinases; Tissue inhibitors of metalloproteinases; Renal cellcarcinoma; Metastasis; Survival
AB Degradation of the extracellular matrix is a prerequisite for the processes of cancer cell invasion and metastasis. The purpose of our study was to assess the association of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9) and their inhibitors (TIMP-1 and TIMP-2) with renal cell carcinoma (RCC) progression and cancer-specific survival (CSS), using immunohistochemical analysis of 60 formalin- fixed, paraffin-embedded sections of tumor tissue and normal tissue near the tumor from surgical T1-3bN0 M0 RCC specimens. Significant overexpression of MMP-2 in tumor and normal tissue was correlated with advanced stages, tumor size, sarcomatous differentiation and clinical symptoms. Overall survival was 31.7% (55.2% M0, 9.7% M1) and CSS 56.7%(100% M0, 16.1% M1) with a follow-up of 76 (5–230) months. Fuhrman grade [HR 2.87 (95% CI: 1.28–6.45); p = 0.01], tumor size [HR 1.13 (95% CI: 1.03–1.26); p = 0.009] and low TIMP-2 expression [HR 0.35 (95% CI: 0.16–0.78); p = 0.01] were independent predictive factors of CSS and stratified the patients into three groups with different rates of 10-year CSS; [100%, 73.9% and 20.5% for the good, intermediate and poor prognosis group respectively (p = 0.000006)] . This study offers strong evidence that TIMP-2 expression in tumor tissue may play a crucial role in progression and poor prognosis in human localized and locally advanced RCC.
C1 [Beardo, Pastora] Araba University Hospital, Department of Urology, c/ Jose Atxotegi s/n, 01009 Vitoria-Gasteiz, Araba, Spain.
[Cacho, Truan David] Marques de Valdecilla University Hospital, Department of Urology, Av. Valdecilla 25, 39008 Santander, Cantabria, Spain.
[Izquierdo, Laura] Clinic Hospital, Department of Urology, c/ Villarroel 170, 08036 Barcelona, Cataluna, Spain.
[Alcover-Garcia, Bautista Joan] Clinic Hospital, Department of Urology, c/ Villarroel 170, 08036 Barcelona, Cataluna, Spain.
[Alcaraz, Antonio] Clinic Hospital, Department of Urology, c/ Villarroel 170, 08036 Barcelona, Cataluna, Spain.
[Extramiana, Javier] Araba University Hospital, Department of Urology, c/ Jose Atxotegi s/n, 01009 Vitoria-Gasteiz, Araba, Spain.
[Mallofre, Carmen] Universitat Autonoma of Barcelona and Clinic Hospital, Department of Pathology, c/ Villarroel 170, 08036 Barcelona, Cataluna, Spain.
RP Beardo, P (reprint author), Araba University Hospital, Department of Urology, 01009 Vitoria-Gasteiz, Spain.
EM beardo.pastora@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 289
EP 299
DI 10.1007/s12253-017-0339-7
PG 11
ER
PT J
AU Awasthi, A
Kumar, P
Srikanth, VCh
Sahi, Sh
Puria, R
AF Awasthi, Ankita
Kumar, Pharvendra
Srikanth, V Chittur
Sahi, Shakti
Puria, Rekha
TI Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mTOR; Kinase inhibitor; Drug development; Docking; Natural Compound
ID mTOR; Kinase inhibitor; Drug development; Docking; Natural Compound
AB Colorectal cancer (CRC) is one of the most prevalent cancers diagnosed worldwide. Despite recent advances, resistance to cytotoxic and targeted therapy remains one of the greatest challenges in long-term management of colorectal cancer therapy. Recently established role of mTOR signaling in proliferation of CRC has incited for evaluation of mTOR kinase specific inhibitors in CRC therapy. Second generation mTOR kinase inhibitors including Torin2 has demonstrated efficient anticancer properties against variety of cancers and are in various stages of drug development. The time and financial constraints concomitant from discovery to development of efficient chemical inhibitors has redirected attention towards investigation of wide spread naturally occurring largely inexpensive compounds for their therapeutic potential. One such naturally occurring compound acetophenone derivative polyphenolic compound 2, 6-Dihydroxyacetophenone (DHAP) inhibits cell growth in different conditions.We investigated anticancer properties of both Torin2 and DHAP against colorectal cancer in HCT8 cell lines. Both Torin2 and DHAP inhibited growth of CRC cells at different concentrations by restricting multiple cellular functions e.g., cell cycle progression, cell migration and induced apoptosis. Treatment of HCT8 cells with natural compound DHAP resulted in reduced expression of mTOR pathway specific genes p70S6K1 and AKT1. In silico docking studies showed affinity of DHAP to mTOR kinase like Torin2. Taken together, our result vouches for role of Torin2 in CRC therapy and recommends DHAP an mTOR inhibitor, as a potential lead in the development of new therapeutic regimes against colorectal cancer.
C1 [Awasthi, Ankita] Gautam Buddha University, School of Biotechnology, Greater NOIDA, 201312 Gautam Budh Nagar, India.
[Kumar, Pharvendra] NCR Biotech Cluster, Regional Centre for Biotechnology, 3rd Milestone, Gurgaon-Faridabad Highway, Village BhankariFaridabad, Haryana, India.
[Srikanth, V Chittur] NCR Biotech Cluster, Regional Centre for Biotechnology, 3rd Milestone, Gurgaon-Faridabad Highway, Village BhankariFaridabad, Haryana, India.
[Sahi, Shakti] Gautam Buddha University, School of Biotechnology, Greater NOIDA, 201312 Gautam Budh Nagar, India.
[Puria, Rekha] Gautam Buddha University, School of Biotechnology, Greater NOIDA, 201312 Gautam Budh Nagar, India.
RP Puria, R (reprint author), Gautam Buddha University, School of Biotechnology, 201312 Gautam Budh Nagar, India.
EM rpuria@gbu.ac.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 301
EP 309
DI 10.1007/s12253-017-0347-7
PG 9
ER
PT J
AU Ding, Y
Sun, Ch
Li, J
Hu, L
Li, M
Liu, J
Pu, L
Xiong, Sh
AF Ding, Yangyang
Sun, Cheng
Li, Jingrong
Hu, Linhui
Li, Manman
Liu, Jun
Pu, Lianfang
Xiong, Shudao
TI The Significance of Long Non-coding RNA HULC in Predicting Prognosis and Metastasis of Cancers: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lncRNA; HULC; Neoplasms; Prognosis; Metastasis; Meta-analysis
ID lncRNA; HULC; Neoplasms; Prognosis; Metastasis; Meta-analysis
AB Long non-coding RNAs (lncRNAs) have been demonstrated that they not only play important roles in tumorgenicity but also associate with cancer prognosis. Recently, highly up-regulated in liver cancer (HULC) is abnormally expressed in liver cancer and other cancers, and participated in cancers progression; however, it is unclear whether its expression is associated with prognosis. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value and metastasis of HULC in various cancer patients. The meta-analysis was performed using a systematic search of PubMed,Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to assess its prognosis and metastasis in human cancer. A total of 1134 patients from 11 studies were included. The results indicated that overexpression of HULC was associated with poor overall survival (OS) (HR = 1.89, 95% CI: 1.32–2.47). Furthermore, subgroup analysis showed that cancer type (digestive system cancer or non-digestive system cancers) and sample size (more or less than 100) significantly associated between HULC and OS. In addition, overexpression of HULC expression was significantly associated with metastasis in cancers (HR = 2.67, 95% CI: 0.94– 4.39). The meta-analysis indicated that lncRNA HULC could serve as a new molecular marker for cancer prognosis and metastasis.
C1 [Ding, Yangyang] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
[Sun, Cheng] The Second Hospital of Anhui Medical University, Department of PharmacologyHefei, Anhui, China.
[Li, Jingrong] The Second Hospital of Anhui Medical University, Department of EmergencyHefei, Anhui, China.
[Hu, Linhui] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
[Li, Manman] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
[Liu, Jun] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
[Pu, Lianfang] The Third People’s Hospital of Bengbu, Department of HematologyBengbu, Anhui, China.
[Xiong, Shudao] The Second Hospital of Anhui Medical University, Department of Hematology / Hematological LabHefei, Anhui, China.
RP Xiong, Sh (reprint author), The Second Hospital of Anhui Medical University, Department of Hematology / Hematological Lab, Hefei, China.
EM xshdao@ahmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 311
EP 318
DI 10.1007/s12253-017-0351-y
PG 8
ER
PT J
AU Legras, A
Roussel, H
Mangiameli, G
Arame, A
Grand, B
Pricopi, C
Badia, A
Gibault, L
Badoual, C
Fabre, E
Laurent-Puig, P
Blons, H
Le Pimpec-Barthes, F
AF Legras, Antoine
Roussel, Helene
Mangiameli, Giuseppe
Arame, Alex
Grand, Bertrand
Pricopi, Ciprian
Badia, Alain
Gibault, Laure
Badoual, Cecile
Fabre, Elizabeth
Laurent-Puig, Pierre
Blons, Helene
Le Pimpec-Barthes, Francoise
TI Mutational Diversity of Lung Cancer and Associated Lymph Nodes. An Exploratory Prospective Study of 4 Resected cIIIA-N2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung neoplasms; Lymph nodes; Genetics; Biomarkers; tumour; High-throughput nucleotide sequencing
ID Lung neoplasms; Lymph nodes; Genetics; Biomarkers; tumour; High-throughput nucleotide sequencing
AB Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected. Samples (tumour and paired LN) were analysed for PD1, PD-L1 and CD8 immunostaining. Somatic mutation testing was performed by deep targeted next generation sequencing (NGS), with the AmpliSeq™ Colon and Lung Cancer Panel (LifeTechnology). A total of 9 primary lung cancer samples and 10 LN stations were analysed. For each cancer, we found 2 mutations, with allelic ratios from 3% to 72%. Mutational patterns were heterogeneous for 2 primary tumours. In 3 cases, mutations observed in the primary tumour were not found in LN metastases (ALK, FGFR3, MET). Inversely, in 1 case, a KRAS mutation was found in LN but not in the primary tumour. All primary tumours were found PD-L1 positive while CD8+ Tcells infiltrate varied. In the different examined LN samples, PD-L1 expression, CD8+ and PD1+ Tcells infiltrate were not similar to the primary tumour. This preliminary prospective study shows the diversity of intra-tumour and LN mutations using routinelyused targeted NGS, concerning both mutated gene and allelic ratio. Further studies are needed to evaluate its prognostic impact.
C1 [Legras, Antoine] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Roussel, Helene] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Pathology DepartmentParis, France.
[Mangiameli, Giuseppe] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Arame, Alex] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Grand, Bertrand] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Pricopi, Ciprian] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Badia, Alain] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
[Gibault, Laure] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Pathology DepartmentParis, France.
[Badoual, Cecile] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Pathology DepartmentParis, France.
[Fabre, Elizabeth] Paris-Descartes University, Sorbonne Paris Cite University, Saints-Peres Research Center, INSERM UMR-S1147, CNRS SNC 5014Paris, France.
[Laurent-Puig, Pierre] Paris-Descartes University, Sorbonne Paris Cite University, Saints-Peres Research Center, INSERM UMR-S1147, CNRS SNC 5014Paris, France.
[Blons, Helene] Paris-Descartes University, Sorbonne Paris Cite University, Saints-Peres Research Center, INSERM UMR-S1147, CNRS SNC 5014Paris, France.
[Le Pimpec-Barthes, Francoise] Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 20 rue Leblanc, 75908 Paris, France.
RP Le Pimpec-Barthes, F (reprint author), Assistance Publique Hopitaux de Paris, Georges Pompidou European Hospital, Thoracic Surgery and Lung Transplantation Department, 75908 Paris, France.
EM francoise.lepimpec-barthes@aphp.fr
CR Asamura H, Chansky K, Crowley J et al, 2015, The International Association for the Study of Lung Cancer lung cancer staging project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol 10:1675–1684
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 319
EP 325
DI 10.1007/s12253-017-0352-x
PG 7
ER
PT J
AU Yu, Yh
Wei, Chy
Qin, Qh
Mo, Qg
Huang, Z
Lian, B
AF Yu, Ying-hua
Wei, Chang-yuan
Qin, Qing-hong
Mo, Qin-guo
Huang, Zhen
Lian, Bin
TI Efficacy of Iodine-125 Seed Implantation in Locoregionally Recurrent and Unresectable Breast Cancer: a Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Iodine-125 seed implantation; Brachytherapy; Locoregionally; Unresectable; Breast cancer
ID Iodine-125 seed implantation; Brachytherapy; Locoregionally; Unresectable; Breast cancer
AB The management of locoregionally recurrent and unresectable breast cancer is a therapeutic challenge. This retrospective study aimed to assess the efficacy of 125I seed implantation brachytherapy as a palliative management in locoregionally recurrent breast cancer. We analyzed 36 locoregionally recurrent and unresectable breast cancers in our hospital between 2012 and 2016. All patients were treated with CT-guided 125I seed permanent implantation. The dose distribution of 125I seeds was calculated using a computerized treatment planning system. Complete response, partial response, stable disease, and local tumor control rates were calculated. Long-term efficacy was assessed based on survival rates ranging from 1 to 4 years. The follow-up period ranged from 6 to 53 months. The median local control was 28 months (95% CI: 16.2–39.8 months). The percentage of patients who showed 6-month, 1-year, 2-year, and 3-year local control was 97.2%, 77.8%, 52.8%, and 33.3%, respectively. Median survival time for all patients was 48 months (95% CI: 40.9– 55.1 months); 1-year, 2-year, 3-year, and 4-year survival rates were 97.2%, 80.6%, 63.9%, and 46.5%, respectively. Pain relief response rate was 88.9%.No serious complications were detected during the follow-up period. The results of this study demonstrate that 125I seed implantation could be considered a feasible and promising minimally invasive therapy for locoregionally recurrent and unresectable breast carcinoma.
C1 [Yu, Ying-hua] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
[Wei, Chang-yuan] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
[Qin, Qing-hong] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
[Mo, Qin-guo] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
[Huang, Zhen] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
[Lian, Bin] Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, NO. 71, He Di Lu, 530021 Nanning, Guangxi, China.
RP Wei, Chy (reprint author), Affiliated Tumor Hospital of Guangxi Medical University, Departmant of Breast Surgery, 530021 Nanning, China.
EM weicy63@aliyun.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 327
EP 332
DI 10.1007/s12253-017-0361-9
PG 6
ER
PT J
AU Polom, K
Das, K
Marrelli, D
Roviello, G
Pascale, V
Voglino, C
Rho, H
Tan, P
Roviello, F
AF Polom, Karol
Das, Kakoli
Marrelli, Daniele
Roviello, Giandomenico
Pascale, Valeria
Voglino, Costantino
Rho, Henry
Tan, Patrick
Roviello, Franco
TI KRAS Mutation in Gastric Cancer and Prognostication Associated with Microsatellite Instability Status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Stomach cancer; KRAS mutation; Mismatch repair deficiency; Molecular; Prognosis
ID Stomach cancer; KRAS mutation; Mismatch repair deficiency; Molecular; Prognosis
AB Microsatellite instability (MSI) is one of the subgroups based on the new molecular classification of gastric cancer (GC). In this study, we analyzed the role of KRAS status in MSI GC and the impact of MSI status on KRAS mutation. We performed analysis on 595 GC patients. Polymerase chain reaction (PCR) was used for the screening of KRAS mutation (exon 2) and 5 quasi-monomorphic mononucleotide repeats, namely, BAT-26, BAT-25, NR -24, NR-21, and NR-27 were used to determine the MSI status. The KRAS and MSI status were then compared with clinicopathologic data of the GC patients. MSI GC was found in 20.3% of all cases. KRAS mutation was seen in 24 patients; 18 were MSI (75%) and 6 were microsatellite stable (MSS) (25%). MSI GC patients with KRAS mutation were older and mostly female, but MSS presented more advanced Tand N stage of the disease, more cardia tumors, and adjuvant treatment. Five-year survival was 72.2% for KRAS mutation patients with MSI and 0% for MSS (p < 0.001). Although KRAS mutations in GC are linked with MSI in the majority of cases, KRAS mutations with MSS status presented with a poor prognosis and a worse outcome. In multivariate analysis, MSI was associated with better survival (p < 0.001) but KRAS was with worse survival (p = 0.304). Our study suggests that KRAS mutations are based on MSI status rather than different codon subtypes ofmutation, and such a division could be used to determine the GC patient outcome.
C1 [Polom, Karol] University of Siena, General Surgery and Surgical Oncology Department, viale Bracci 16, 53-100 Siena, Italy.
[Das, Kakoli] Duke-NUS Medical School, Cancer and Stem Cell Biology Programme, 8 College Road, 169857 Singapore, Singapore.
[Marrelli, Daniele] University of Siena, General Surgery and Surgical Oncology Department, viale Bracci 16, 53-100 Siena, Italy.
[Roviello, Giandomenico] San Donato Hospital, Department of Oncology, Medical Oncology Unit, Via Nenni 20, 52100 Arezzo, Italy.
[Pascale, Valeria] University of Siena, General Surgery and Surgical Oncology Department, viale Bracci 16, 53-100 Siena, Italy.
[Voglino, Costantino] University of Siena, General Surgery and Surgical Oncology Department, viale Bracci 16, 53-100 Siena, Italy.
[Rho, Henry] Poznan University of Medical SciencesPoznan, Poland.
[Tan, Patrick] Duke-NUS Medical School, Cancer and Stem Cell Biology Programme, 8 College Road, 169857 Singapore, Singapore.
[Roviello, Franco] University of Siena, General Surgery and Surgical Oncology Department, viale Bracci 16, 53-100 Siena, Italy.
RP Polom, K (reprint author), University of Siena, General Surgery and Surgical Oncology Department, 53-100 Siena, Italy.
EM polom.karol@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 333
EP 340
DI 10.1007/s12253-017-0348-6
PG 8
ER
PT J
AU Ren, K
Xin, G
Xiao, M
He, W
Kang, J
AF Ren, Ke
Xin, Gou
Xiao, Mingzhao
He, Weiyang
Kang, Jian
TI Pim-2 Cooperates with Downstream Factor XIAP to Inhibit Apoptosis and Intensify Malignant Grade in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pim-2; XIAP; Apoptosis; Malignant grade
ID Pim-2; XIAP; Apoptosis; Malignant grade
AB To find the exact downstream effector of Pim-2 pathway in prostate cancer cells, and to determine the means by which it affects prostate cancer. XIAP, Pim-2 and p-eIF4B expressions were detected in PCA and BPH tissues. Then the Pim-2 and XIAP expressions were manipulated using transfection or RNAi in prostatic cells. Finally, Pim-2/eIF4B/XIAP levels were examined in PCA tissues with different clinicopathologic features. XIAP was significantly higher in PCA than in BPH tissues. When Pim-2 was transfected into noncancerous prostate epithelial cells RWPE-1, Pim-2, p-eIF4B and XIAP were all significantly increased and the apoptosis rate was significantly decreased. When XIAP was transfected into RWPE-1 cells, XIAP was significantly increased with no impact on Pim-2, p-eIF4B and the apoptosis rate. When Pim-2 SiRNA was transfected into prostate cancer cells PC-3, Pim-2, p-eIF4B and XIAP were significantly decreased and the apoptosis rate was significantly increased. When XIAP SiRNA was transfected into PC-3 cells, XIAP was significantly decreased with no impact on Pim-2, p-eIF4B and apoptosis rate. Pim-2, p-eIF4B and XIAP were all significantly higher in PCA tissues with GS ≥8 than those with GS ≤7. XIAP is the downstream factor of Pim-2 pathway in prostate cancer cells. Pim-2 and XIAP cooperate in inhibiting the apoptosis of prostate cancer cells. The activation of Pim-2 pathway may predict higher GS in prostate cancer.
C1 [Ren, Ke] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 1 Youyi Road, Yuzhong Distrct, 400016 Chongqing, China.
[Xin, Gou] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 1 Youyi Road, Yuzhong Distrct, 400016 Chongqing, China.
[Xiao, Mingzhao] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 1 Youyi Road, Yuzhong Distrct, 400016 Chongqing, China.
[He, Weiyang] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 1 Youyi Road, Yuzhong Distrct, 400016 Chongqing, China.
[Kang, Jian] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 1 Youyi Road, Yuzhong Distrct, 400016 Chongqing, China.
RP Ren, K (reprint author), Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
EM renke_rk@163.com
CR White E, 2003, The Pims and outs of survival signaling: role for the Pim-2 protein kinase in the suppression of apoptosis by cytokines. Genes Dev 17(15):1813–1816. , DOI 10.1101/gad. 1123103
Ren K, Gou X, Xiao M,WangM, Liu C, Tang Z, HeW(2013, The over-expression of Pim-2 promote the tumorigenesis of prostatic carcinoma through phosphorylating eIF4B. Prostate 73(13):1462– 1469. , DOI 10.1002/pros.22693
Yang J, Wang J, Chen K, Guo G, Xi R, Rothman PB, Whitten D, Zhang L, Huang S, Chen JL, 2013, eIF4B phosphorylation by pim kinases plays a critical role in cellular transformation by Abl oncogenes. Cancer Res 73(15):4898–4908. , DOI 10.1158/ 0008-5472.CAN-12-4277
Shahbazian D, Parsyan A, Petroulakis E, Topisirovic I, Martineau Y, Gibbs BF, SvitkinY, SonenbergN(2010, Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. Mol Cell Biol 30(6):1478–1485. , DOI 10.1128/MCB. 01218-09
Swanson GP, Basler JW, 2010, Prognostic factors for failure after prostatectomy. J Cancer 2:1–19 PMID: 21197260
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Ayala GE, Dai H, Ittmann M, Li R, Powell M, Frolov A, Wheeler TM, Thompson TC, Rowley D, 2004, Growth and survival mechanisms associated with perineural invasion in prostate cancer. Cancer Res 64(17):6082–6090. , DOI 10.1158/0008- 5472.CAN-04-0838
Kapelko-Slowik K, Urbaniak-Kujda D, Wolowiec D, Jazwiec B, Dybko J, Jakubaszko J, Slowik M, Kuliczkowski K, 2013, Expression of PIM-2 and NF-κB genes is increased in patients with acute myeloid leukemia, AML, and acute lymphoblastic leukemia, ALL, and is associated with complete remission rate and overall survival. Postepy Hig Med Dosw, Online, 67:553–559 PMID: 23752607
Asano J, Nakano A, Oda A, Amou H, Hiasa M, Takeuchi K, Miki H, Nakamura S, Harada T, Fujii S, Kagawa K, Endo I, Yata K, Sakai A, Ozaki S, Matsumoto T, Abe M, 2011, The serine/ threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells. Leukemia 25(7):1182–1188. , DOI 10.1038/ leu.2011.60
Ren K, Zhang W, Shi Y, Gong J, 2010, Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NFkappaB pathway. Pathol Oncol Res 16(2):229–237. , DOI 10.1007/s12253-009-9215-4
Park YH, Seo SY, Lee E, JH K, Kim HH, Kwak C, 2013, Simvastatin induces apoptosis in castrate resistant prostate cancer cells by deregulating nuclear factor-κB pathway. J Urol 189(4):1547–1552. , DOI 10.1016/j.juro.2012. 10.030
Kim HR, Park CG, Jung JY, 2014, Acacetin, 5,7-dihydroxy-4′- methoxyflavone, exhibits in vitro and in vivo anticancer activity through the suppression of NF-κB/Akt signaling in prostate cancer cells. Int J Mol Med 33(2):317–324. , DOI 10.3892/ijmm. 2013.1571
Zhang P, Chen L, Song Y, Li X, Sun Y, Xiao Y, Xing Y, 2016, Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway. Exp Cell Res 347(2):350–359. , DOI 10.1016/j.yexcr.2016. 08.019
Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC, Glinsky GV, 2005, Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 65:2378–2386. , DOI 10.1158/0008-5472. CAN-04-2649
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 341
EP 348
DI 10.1007/s12253-017-0353-9
PG 8
ER
PT J
AU Dvorak, K
Higgins, A
Palting, J
Cohen, M
Brunhoeber, P
AF Dvorak, Katerina
Higgins, Amanda
Palting, John
Cohen, Michael
Brunhoeber, Patrick
TI Immunohistochemistry with Anti-BRAF V600E (VE1) Mouse Monoclonal Antibody is a Sensitive Method for Detection of the BRAF V600E Mutation in Colon Cancer: Evaluation of 120 Cases with and without KRAS Mutation and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BRAF V600E; KRAS; Colon cancer; DNA sequencing; Immunohistochemistry
ID BRAF V600E; KRAS; Colon cancer; DNA sequencing; Immunohistochemistry
AB The major aim of this study was to evaluate the performance of anti-BRAF V600E (VE1) antibody in colorectal tumors with and without KRAS mutation. KRAS and BRAF are two major oncogenic drivers of colorectal cancer (CRC) that have been frequently described as mutually exclusive, thus the BRAF V600E mutation is not expected to be present in the cases with KRAS mutation. In addition, a review of 25 studies comparing immunohistochemistry (IHC) using the anti-BRAF V600E (VE1) antibody with BRAF V600E molecular testing in 4041 patient samples was included. One-hundred and twenty cases with/without KRAS or BRAF mutations were acquired. The tissue were immunostained with anti-BRAF V600E (VE1) antibody with OptiView DAB IHC detection kit. The KRAS mutated cases with equivocal immunostaining were further evaluated by Sanger sequencing for BRAF V600E mutation. Thirty cases with BRAF V600E mutation showed unequivocal, diffuse, uniform, positive cytoplasmic staining and 30 cases with wild-type KRAS and BRAF showed negative staining with anti-BRAF V600E (VE1) antibody. Out of 60 cases with KRAS mutation, 56 cases (93.3%) were negative for BRAF V600E mutation by IHC. Four cases showed weak, equivocal, heterogeneous, cytoplasmic staining along with nuclear staining in 25–90% of tumor cells. These cases were confirmed to be negative for BRAF V600E mutation by Sanger sequencing. Overall, IHC with anti-BRAF V600E (VE1) antibody using recommended protocol with OptiView detection is optimal for detection of BRAF V600E mutation in CRC. Our data are consistent with previous reports indicating that KRAS and BRAF V600E mutation are mutually exclusive.
C1 [Dvorak, Katerina] Roche Tissue Diagnostics, 1910 E. Innovation Park DriveTucson, AZ, USA.
[Higgins, Amanda] Roche Tissue Diagnostics, 1910 E. Innovation Park DriveTucson, AZ, USA.
[Palting, John] Roche Tissue Diagnostics, 1910 E. Innovation Park DriveTucson, AZ, USA.
[Cohen, Michael] Roche Tissue Diagnostics, 1910 E. Innovation Park DriveTucson, AZ, USA.
[Brunhoeber, Patrick] Roche Tissue Diagnostics, 1910 E. Innovation Park DriveTucson, AZ, USA.
RP Dvorak, K (reprint author), Roche Tissue Diagnostics, Tucson, USA.
EM katerina.dvorak@roche.com
CR Adackapara CA, Sholl LM, Barletta JA et al, 2013, Immunohistochemistry using the BRAF V600E mutation-specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma. Histopathology 63:187–193
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Bledsoe JR, Kamionek M, Mino-Kenudson M, 2014, BRAF V600E immunohistochemistry is reliable in primary and metastatic colorectal carcinoma regardless of treatment status and shows high intratumoral homogeneity. Am J Surg Pathol 38:1418–1428
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Koinuma K, Shitoh K,Miyakura Yet al, 2004, Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas. Int J Cancer 108:237–242 1 9 . Kuan SF, Na v i n a S, Cressman KL e t a l, 2014, Immunohistochemical detection of BRAF V600E mutant protein using the VE1 antibody in colorectal carcinoma is highly concordant with molecular testing but requires rigorous antibody optimization. Hum Pathol 45:464–472 20. Lasota J, Kowalik A,Wasag B et al, 2014, Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach. Am J Surg Pathol 38:1235–1241 21. Loes IM, Immervoll H, Angelsen JH et al, 2015, Performance comparison of three BRAF V600E detection methods in malignant melanoma and colorectal cancer specimens. Tumour Biol 36:1003– 1013 22. Marin C, Beauchet A, Capper D et al, 2013, Detection of BRAF p.V600E Mutations in Melanoma by Immunohistochemistry Has a Good Interobserver Reproducibility. 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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 349
EP 359
DI 10.1007/s12253-017-0344-x
PG 11
ER
PT J
AU Dura, M
Nemejcova, K
Jaksa, R
Bartu, M
Kodet, O
Ticha, I
Michalkova, R
Dundr, P
AF Dura, Miroslav
Nemejcova, Kristyna
Jaksa, Radek
Bartu, Michaela
Kodet, Ondrej
Ticha, Ivana
Michalkova, Romana
Dundr, Pavel
TI Expression of Glut-1 in Malignant Melanoma and Melanocytic Nevi: an Immunohistochemical Study of 400 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glut-1; Malignant melanoma; Melanocytic nevus; Immunohistochemistry; Follow-up
ID Glut-1; Malignant melanoma; Melanocytic nevus; Immunohistochemistry; Follow-up
AB The glucose transporter-1 (Glut-1) is a cell membrane glycoprotein involved in glucose uptake. An increased expression of Glut-1 is an important cell adaptation mechanism against hypoxia. An upregulation of Glut- 1 can be found in several types of malignant tumors, which are able to reprogram their metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect). However, the data regarding melanocytic lesions is equivocal. We performed comprehensive immunohistochemical analysis of the Glut-1 expression in 225 malignant melanomas (MM) and 175 benign nevi. Only the membranous expression of Glut-1 was regarded as positive. The expression of Glut-1 (the cut-off for positivity was determined as H-score 15) was found in 69/225 malignant melanomas. The number of positive cases and the H-score of Glut-1 increased where there was a higher Breslow thickness (p < 0.00001) when comparing pT1- pT4 MM groups. All benign nevi were classified as negative. In conclusion, the membranous expression of Glut-1 is a common feature of a malignant melanoma but this type of expression is very rare in benign melanocytic nevi. Our results suggest that the membranous expression of Glut-1 can be used as a surrogate marker in the assessing of the biological nature of benign and malignant melanocytic lesions. However, despite its high specificity, the sensitivity of this marker is relatively low. Moreover, due to the fact that the increased expression of Glut-1 correlates with a shorter survival period (10-year disease free survival, recurrence free survival and metastasis free survival and MFS), it can be used as a prognostically adverse factor.
C1 [Dura, Miroslav] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Nemejcova, Kristyna] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Jaksa, Radek] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Bartu, Michaela] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Kodet, Ondrej] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Dermatology and VenereologyPrague, Czech Republic.
[Ticha, Ivana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Michalkova, Romana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 12800 Prague, Czech Republic.
EM pdundr@seznam.cz
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 361
EP 368
DI 10.1007/s12253-017-0363-7
PG 8
ER
PT J
AU Gao, LM
Wang, F
Zheng, Y
Fu, ZZ
Zheng, L
Chen, LL
AF Gao, Li-Ming
Wang, Fang
Zheng, Yue
Fu, Zhan-Zhao
Zheng, Lei
Chen, Lan-Lan
TI Roles of Fibroblast Activation Protein and Hepatocyte Growth Factor Expressions in Angiogenesis and Metastasis of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Fibroblast activation protein; Hepatocyte growth factor; Angiogenesis; Metastasis; Microvessel density
ID Gastric cancer; Fibroblast activation protein; Hepatocyte growth factor; Angiogenesis; Metastasis; Microvessel density
AB This study aims to explore the roles of fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) expressions in the angiogenesis and metastasis of gastric cancer (GC). From May 2012 to December 2015, 110 GC patients who received surgical treatment in the First Hospital of Qinhuangdao were selected. The HGF and FAP expressions in 110 cases of GC, 130 cases of normal gastric mucosa and 115 cases of gastric ulcer were detected by streptavidinperosidase (SP) method. Venous blood HGF level of GC patients was tested by enzyme-linked immunosorbent assay (ELISA). The micro-vessel number of the patients in the three groups were calculated and analyzed. In GC group, positive expression rates of FAP and HGF protein were 61.8% and 67.3% respectively, which were both higher than those in normal gastric mucosa and gastric ulcer groups. The microvessel numbers in patients of the normal gastric mucosa and gastric ulcer groups are far less than that in GC group. FAP, HGF and micro-vessel density (MVD) were significantly correlated with infiltration depth, tumor-node-metastasis (TNM) staging, lymph node metastasis (LNM) and distant metastasis. The results of ELISA showed that serum HGF level was related to tumor size, infiltration degree, TNM staging, LNM and distant metastasis. FAP and HGF expressions in GC were positively correlated with MVD, and the expressions of FAP and HGF in GC were in positive correlation. Our study provided evidence that high FAP and HGF expressions may be positively correlated with the angiogenesis and metastasis of GC.
C1 [Gao, Li-Ming] First Hospital of Qinhuangdao, Department of Oncology, No. 258 Wenhua Road, Haigang District, 066000 Qinhuangdao, Hebei Province, China.
[Wang, Fang] First Hospital of Qinhuangdao, Department of Oncology, No. 258 Wenhua Road, Haigang District, 066000 Qinhuangdao, Hebei Province, China.
[Zheng, Yue] First Hospital of Qinhuangdao, Department of Gastroenterology, 066000 Qinhuangdao, Hebei Province, China.
[Fu, Zhan-Zhao] First Hospital of Qinhuangdao, Department of Oncology, No. 258 Wenhua Road, Haigang District, 066000 Qinhuangdao, Hebei Province, China.
[Zheng, Lei] First Hospital of Qinhuangdao, Department of Oncology, No. 258 Wenhua Road, Haigang District, 066000 Qinhuangdao, Hebei Province, China.
[Chen, Lan-Lan] First Hospital of Qinhuangdao, Department of Oncology, No. 258 Wenhua Road, Haigang District, 066000 Qinhuangdao, Hebei Province, China.
RP Fu, ZZ (reprint author), First Hospital of Qinhuangdao, Department of Oncology, 066000 Qinhuangdao, China.
EM Tshgaoliming@163.com
CR Shirahata A, Sakata M, Kitamura Y, Sakuraba K, Yokomizo K, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G, Nemoto H, Hibi K, 2010, MACC 1 as a marker for peritoneal-disseminated gastric carcinoma. Anticancer Res 30:3441–3444
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 369
EP 376
DI 10.1007/s12253-017-0359-3
PG 8
ER
PT J
AU Song, XF
Wang, QH
Huo, R
AF Song, Xiao-Fei
Wang, Qi-Hua
Huo, Ran
TI Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 through the Wnt Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA-708; Epithelial-mesenchymal transition; Melanoma cells; Lymphoid enhancer-binding factor-1; Wnt signaling pathway
ID MicroRNA-708; Epithelial-mesenchymal transition; Melanoma cells; Lymphoid enhancer-binding factor-1; Wnt signaling pathway
AB This study was conducted in order to elucidate the role microRNA-708 (miR-708) plays between proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) involving melanoma cells by targeting using LEF1 through the Wnt signaling pathway. Male Kunming mice were selected and subsequently divided into normal and model groups to take part in this study. Following cell line selection, the B16 cells with the highest miR-708 expression were selected and assigned into the control, blank, negative control (NC), miR-708 mimic, miR-708 inhibitor, siRNA-LEF1, and miR-708 inhibitor + siRNA-LEF1 groups. A Bioinformatics Web service and dual-luciferase reporter assay were conducted in order to determine the relationship between LEF1 and miR-708. The RT-qPCR method was performed in order to detect the miR-708 expression and mRNA expressions of LEF1, β-catenin, Wnt3a, N-cadherin, Bcl-2, Bax, Caspase3, Ecadherin, and western blotting was used in order to detect the protein expressions of these genes. MTT assay, scratch test, Transwell assay, and flow cytometry were all conducted in order to detect the cell proliferation, migration, invasion, and cycle/apoptosis, respectively. LEF1 was verified as the target gene of miR-708. In comparison with the normal group, the model group had reduced expressions of miR-708, Bax, Caspase3, and E-cadherin, while showing elevated expressions of LEF1, β-catenin, Bcl-2, Wnt3a, and N-cadherin. In comparison to the blank and control groups, the miR-708, mimic, and siRNA-LEF1 groups had elevated expressions of Bax, Caspase3, and Ecadherin, while also showing enhanced cell apoptosis. The miR-708, mimic, and siRNA-LEF1 groups also had decreased expressions of LEF1, β-catenin, Bcl-2, Wnt3a, and N-cadherin, and reduced optical density value 48 h and 72 h after transfection. Besides, these two groups showed declined cell migration and invasion, as well as lengthened G0/G1 phase (increased cell number) and shortened S phase (decreased cell number). Our findings demonstrated that an overexpressed miR-708 inhibits the proliferation, invasion, migration, and EMT, but also promotes the apoptosis of melanoma cells by targeting LEF1 through the suppression of the Wnt signaling pathway.
C1 [Song, Xiao-Fei] Shandong Provincial Hospital Affiliated to Shandong University, Department of Aesthetic Plastic and Burn Surgery, No. 324, Jingwuweiqi Road, 250021 Jinan, China.
[Wang, Qi-Hua] Linyi Dermatology Hospital, Department of Dermatology, 276003 Linyi, China.
[Huo, Ran] Shandong Provincial Hospital Affiliated to Shandong University, Department of Aesthetic Plastic and Burn Surgery, No. 324, Jingwuweiqi Road, 250021 Jinan, China.
RP Huo, R (reprint author), Shandong Provincial Hospital Affiliated to Shandong University, Department of Aesthetic Plastic and Burn Surgery, 250021 Jinan, China.
EM huoran8003@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 377
EP 389
DI 10.1007/s12253-017-0334-z
PG 13
ER
PT J
AU Kakkassery, V
Skosyrski, S
Luth, A
Kleuser, B
van der Giet, vdM
Tate, R
Reinhard, J
Faissner, A
Joachim, S
Kociok, N
AF Kakkassery, Vinodh
Skosyrski, Sergej
Luth, Anja
Kleuser, Burkhard
van der Giet, van der Markus
Tate, Rothwelle
Reinhard, Jacqueline
Faissner, Andreas
Joachim, C. Stephanie
Kociok, Nobert
TI Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Retinoblastoma; Sphingosine-1-phosphate; Chemotherapy resistance
ID Retinoblastoma; Sphingosine-1-phosphate; Chemotherapy resistance
AB Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). Only sphingosine-1-P up-regulation was significantly increased in WERI EtoR (p < 0.01), but not in WERI Rb1 (p > 0.2). Both cell lines upregulate proapoptotic sphingosine after etoposide incubation, but only WERI EtoR produces additional survival favorable sphingosine- 1-P. These data may suggest a role of sphingosine- 1-P in retinoblastoma chemotherapy resistance, although this seems not to be the only resistance mechanism.
C1 [Kakkassery, Vinodh] Charite Universitatsmedizin, Department of OphthalmologyBerlin, Germany.
[Skosyrski, Sergej] Charite Universitatsmedizin, Department of OphthalmologyBerlin, Germany.
[Luth, Anja] University Potsdam, Department of Nutrition SciencePotsdam, Germany.
[Kleuser, Burkhard] University Potsdam, Department of Nutrition SciencePotsdam, Germany.
[van der Giet, van der Markus] Charite Universitatsmedizin, Campus Benjamin Franklin, Department of NephrologyBerlin, Germany.
[Tate, Rothwelle] University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical SciencesGlasgow, UK.
[Reinhard, Jacqueline] Ruhr-University Bochum, Faculty of Biology and Biotechnology, Department of Cell Morphology and Molecular NeurobiologyBochum, Germany.
[Faissner, Andreas] Ruhr-University Bochum, Faculty of Biology and Biotechnology, Department of Cell Morphology and Molecular NeurobiologyBochum, Germany.
[Joachim, C. Stephanie] Ruhr-University Bochum, Department of OphthalmologyBochum, Germany.
[Kociok, Nobert] Charite Universitatsmedizin, Department of OphthalmologyBerlin, Germany.
RP Kakkassery, V (reprint author), Charite Universitatsmedizin, Department of Ophthalmology, Berlin, Germany.
EM vinodh.kakkassery@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 391
EP 399
DI 10.1007/s12253-017-0360-x
PG 9
ER
PT J
AU Toy, H
Etli, O
Celik, EZ
Alikanoglu, SA
AF Toy, Hatice
Etli, Ozlem
Celik, Esin Zeliha
Alikanoglu, Sezgin Arsenal
TI Associations Between Nucleus Size, and Immunohistochemical Galectin-3, Cytokeratine-19 and Hbme-1 Markers in Thyroid Papillary Carcinoma: A Morphometric Analyze
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid carcinoma; Nucleus diameter; Morphometric analyze
ID Papillary thyroid carcinoma; Nucleus diameter; Morphometric analyze
AB This study aimed to evaluate the morphometric measurements in cases with papillary thyroid carcinoma, and determine a cut-off value to support diagnosis. Fifty cases with a diagnosis of papillary thyroid carcinoma (PTC) were included in the study with their Galectine-3, CK-19 and HBME-1 immunohistochemical staining results. Demographic and clinical data gathered from pathology reports, which included demographic information such as patients’ sex, age, macroscopic tumor size, number of tumor focuses; prognostic parameters such as lenfovascular invasion, perineural invasion, thyroid capsule invasion; and results of immunohistochemical CK- 19, Galectin-3 and HBME-1 staining. Longest nuclear diameters of 150 tumor cells and 150 normal thyrocytes of each case were manually measured in an image analysis software, and mean longest nuclear diameters (MLND-TC and MLND-NC), and also tumor cell/normal cell longest nuclear diameter ratio (TC/NC-LNDR) were calculated. MLND-TC was higher than MLND-NC. The cases with higher MLND-TC had increased risk of capsule invasion in case of a negative staining with Galectine-3, HBME-1, or CK-19. When TC/NC-LNDR was high, number of tumor focus tended to be multiple and lymphovascular invasion risk was also increased. Subtypes of PTC were not differed regarding staining patterns. And finally, increased TC/NC-LNDR was associated with increased risk of having poor prognostic factors. The results of this study suggest that MLND-NC, MLND-TC, and TC/NCLNDR are valuable and easy-to-use measures, which can assist routine histology practice.
C1 [Toy, Hatice] Necmettin Erbakan University Meram, Medicine Faculty, Department of PathologyKonya, Turkey.
[Etli, Ozlem] Pendik State Hospital, Department of PathologyIstanbul, Turkey.
[Celik, Esin Zeliha] Selcuk University, Medicine Faculty, Department of PathologyKonya, Turkey.
[Alikanoglu, Sezgin Arsenal] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
RP Toy, H (reprint author), Necmettin Erbakan University Meram, Medicine Faculty, Department of Pathology, Konya, Turkey.
EM haticetoy@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 401
EP 408
DI 10.1007/s12253-017-0337-9
PG 8
ER
PT J
AU Shibuya, I
Takami, M
Miyamoto, A
Karakawa, A
Dezawa, A
Nakamura, Sh
Kamijo, R
AF Shibuya, Isao
Takami, Masamichi
Miyamoto, Arei
Karakawa, Akiko
Dezawa, Akira
Nakamura, Shigeru
Kamijo, Ryutaro
TI In Vitro Study of the Effects of Denosumab on Giant Cell Tumor of Bone: Comparison with Zoledronic Acid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Giant cell tumor of bone; Osteoclast; Bisphosphonate; Denosumab; Bone tumor
ID Giant cell tumor of bone; Osteoclast; Bisphosphonate; Denosumab; Bone tumor
AB Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that contains numerous osteoclasts formed from marrow-derived precursors through receptor activator of nuclear factor κ-B ligand (RANKL), an osteoclast differentiation factor expressed in neoplastic cells of GCTB. Denosumab, a fully human monoclonal antibody targeting RANKL, has recently been used for the treatment of GCTB, and superior treatment effects have been reported. The aimof this work was to elucidate the mechanismof action of denosumab, and the differences between denosumab and zoledronic acid at the level of GCTB cells.We isolated GCTB cells from 3 patients and separated them into osteoclasts, osteoclast precursors and proliferating spindle-shaped stromal cells (the true neoplastic component), and examined the action of denosumab on differentiation, survival and bone resorption activity of osteoclasts. Denosumab and zoledronic acid inhibited osteoclast differentiation from mononuclear cells containing osteoclast precursors. Zoledronic acid inhibited osteoclast survival, whereas an inhibitory effect of denosumab on osteoclast survival was not observed. The inhibitory effect on bone resorption by both agents was confirmed in culture on dentin slices. Furthermore, zoledronic acid showed dosedependent inhibition of cell growth of neoplastic cells whereas denosumab had no inhibitory effect on these cells. Denosumab has an inhibitory effect on osteoclast differentiation, but no inhibitory effects on survival of osteoclasts or growth of neoplastic cells in GCTBs.
C1 [Shibuya, Isao] Showa University, School of Dentistry, Department of Biochemistry, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555 Tokyo, Japan.
[Takami, Masamichi] Showa University, School of Dentistry, Department of Pharmacology, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555 Tokyo, Japan.
[Miyamoto, Arei] Showa University, School of Dentistry, Department of Biochemistry, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555 Tokyo, Japan.
[Karakawa, Akiko] Showa University, School of Dentistry, Department of Pharmacology, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555 Tokyo, Japan.
[Dezawa, Akira] Teikyo University, Mizonokuchi Hospital, Department of Orthopaedic Surgery, 3-8-3 Mizonokuchi, Takatsu-ku, 213-8507 Kawasaki, Kanagawa, Japan.
[Nakamura, Shigeru] Teikyo University, Mizonokuchi Hospital, Department of Orthopaedic Surgery, 3-8-3 Mizonokuchi, Takatsu-ku, 213-8507 Kawasaki, Kanagawa, Japan.
[Kamijo, Ryutaro] Showa University, School of Dentistry, Department of Biochemistry, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555 Tokyo, Japan.
RP Shibuya, I (reprint author), Showa University, School of Dentistry, Department of Biochemistry, 142-8555 Tokyo, Japan.
EM ishibu@med.teikyo-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 409
EP 419
DI 10.1007/s12253-017-0362-8
PG 11
ER
PT J
AU Bulibu, J
Wang, W
Tang, Y
Li, N
Saifuding, K
AF Bulibu, Jilisihan
Wang, Wei
Tang, Yong
Li, Na
Saifuding, Keyoumu
TI Association Between Polymorphisms in the Promoter Region of microRNA-34b/c and the Chemoradiotherapy Efficacy for Locally Advanced Esophageal Squamous Cell Carcinoma in Chinese Han Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA-34b/c; Esophageal squamous cell carcinoma; Promoter region; Polymorphism; Chemoradiotherapy efficacy; Chinese Han population
ID MicroRNA-34b/c; Esophageal squamous cell carcinoma; Promoter region; Polymorphism; Chemoradiotherapy efficacy; Chinese Han population
AB The study aims to explore the association between polymorphisms in the promoter region of microRNA-34b/c (miR-34b/c) and the chemoradiotherapy efficacy for locally advanced esophageal squamous cell carcinoma (ESCC) in Chinese Han population. A total of 175 locally advanced ESCC cases and 186 healthy individuals were enrolled as the case and control groups. Denaturing high performance liquid chromatography (DHPLC) was applied to determine the genotypes of subjects. Subjects in the case group were classified into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR + PR were defined as the sensitive group, and SD + PD were defined as the resistance group. All patients were followed up for 3 ~ 36 months. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of rs4938723 in the promoter region of miR-34b/c in the chemoradiotherapy efficacy for patients with locally advanced ESCC. The distribution of genotype and allele of rs4938723 in the promoter region of miR-34b/c was significantly different between the case and control group (both P < 0.05), and CC genotype and C allele could decrease the risk of ESCC (CC genotype: OR = 0.57, 95% CI = 0.32 ~ 0.99, P = 0.045; C allele: OR = 0.72, 95% CI = 0.54 ~ 0.97, P = 0.032). MiR-34b/c rs4938723 was associated with ESCC TNM staging, differentiation degree, and lymph node metastasis (LNM) for ES CC patients (all P < 0.05). The chemoradiotherapy efficacy of patients with CC genotype was better than that of patients with (TT + TC) genotypes (P < 0.05). ROC curve results showed that the area under curve (AUC), sensitivity and specificity were 0.777, 85.1% and 71.3%, respectively. The average median progression free survival (PFS) of patients with (TT + TC) genotypes was significantly shorter than those patients with CC genotype (P < 0.05). Our study provides evidence that miR-34b/c rs4938723 is closely related with the chemoradiotherapy efficacy for locally advanced ESCC.
C1 [Bulibu, Jilisihan] The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, No. 789, Suzhou East Street, 830000 Urumqi, Xinjiang Uygur Autonomous Region, China.
[Wang, Wei] The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, No. 789, Suzhou East Street, 830000 Urumqi, Xinjiang Uygur Autonomous Region, China.
[Tang, Yong] The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, No. 789, Suzhou East Street, 830000 Urumqi, Xinjiang Uygur Autonomous Region, China.
[Li, Na] The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, No. 789, Suzhou East Street, 830000 Urumqi, Xinjiang Uygur Autonomous Region, China.
[Saifuding, Keyoumu] The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, No. 789, Suzhou East Street, 830000 Urumqi, Xinjiang Uygur Autonomous Region, China.
RP Saifuding, K (reprint author), The Affiliated Tumor Hospital of Xinjiang Medical University, Department of Gastroenterology, 830000 Urumqi, China.
EM saifudingkeyoumu@126.com
CR Chen J, Kwong DL, Cao T, Hu Q, Zhang L,Ming X, Chen J, Fu L, Guan X, 2015, Esophageal squamous cell carcinoma, ESCC): advance in genomics and molecular genetics. Dis Esophagus 28:84– 89
Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, Liu Z, Zhan Q, Liu Y, Yu D, Zhai K, Chang J, Qiao Y, Jin G, Liu Z, Shen Y, Guo C, Fu J, Miao X, Tan W, Shen H, Ke Y, Zeng Y, Wu T, Lin D, 2011, Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet 43:679–684
ZhangX, Li M, Meng X, Kong L, ZhangY,Wei G, Zhang X, Shi F, HuM, Zhang G, Yu J, 2014, Involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. Radiat Oncol 9:64
Cho SH, Shim HJ, Lee SR, Ahn JS, Yang DH, Kim YK, Nam TK, Lee JJ, Kim HJ, Chung IJ, 2008, Concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer. Dis Esophagus 21:697–703
Li DJ, Li HW, He B, Wang GM, Cai HF, Duan SM, Liu JJ, Zhang YJ, Cui Z, Jiang H, 2016, Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma. J BUON 21:1268–1273
Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N,Watanabe M, Baba H, 2009, MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res 15:1915–1922
Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, NakagawaM,Matsubara H, 2010, miR- 145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer 127: 2804–2814
Corney DC, Flesken-Nikitin A, Godwin AK,Wang W, Nikitin AY, 2007, MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433–8438
Suzuki H, Yamamoto E, Nojima M, Kai M, Yamano HO, Yoshikawa K, Kimura T, Kudo T, Harada E, Sugai T, Takamaru H, Niinuma T, Maruyama R, Yamamoto H, Tokino T, Imai K, Toyota M, Shinomura Y, 2010, Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. Carcinogenesis 31:2066–2073
ToyotaM, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, Tokino T, 2008, Epigenetic silencing of microRNA-34b/c and Bcell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 68:4123–4132
Lin Z, Chen L, Song M, Shi KQ, Tang KF, 2014, Association between a polymorphism in miR-34b/c and susceptibility to cancer–a meta-analysis. Asian Pac J Cancer Prev 15:7251–7255
Wang X, Lu X, Fang Y, Chen H, Deng X, Peng C, Li H, Shen B, 2014, Association between miR34b/c polymorphism rs4938723 and cancer risk: a meta-analysis of 11 studies including 6169 cases and 6337 controls. Med Sci Monit 20:1977–1982
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Guo Y, Chen Z, Zhang L, Zhou F, Shi S, Feng X, Li B,Meng X, Ma X, Luo M, Shao K, Li N, Qiu B, Mitchelson K, Cheng J, He J, 2008, Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 68:26–33
Ji TX, Zhi C, Guo XG, Zhou Q,Wang GQ, Chen B,Ma FF, 2015, MiR-34b/c rs4938723 polymorphism significantly decreases the risk of digestive tract cancer: meta-analysis. Asian Pac J Cancer Prev 16:6099–6104
Xu Y, Liu L, Liu J, Zhang Y, Zhu J, Chen J, Liu S, Liu Z, Shi H, Shen H, Hu Z, 2011, A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. Int J Cancer 128:412–417
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Yin J,Wang X, Zheng L, Shi Y,Wang L, Shao A, TangW, Ding G, Liu C, Liu R, Chen S, Gu H, 2013, Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population. PLoS One 8:e80570
Corsini LR, Bronte G, Terrasi M, Amodeo V, Fanale D, Fiorentino E, Cicero G, Bazan V, Russo A, 2012, The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies. Expert Opin Ther Targets 16(Suppl 2):S103–S109
Hermeking H, 2010, The miR-34 family in cancer and apoptosis. Cell Death Differ 17:193–199
Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, Nagashima M, Takenoshita S, Yokota J, Harris CC, 2008, Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res 68:3193–3203
Cho CY, Huang JS, Shiah SG, Chung SY, Lay JD, Yang YY, Lai GM, Cheng AL, Chen LT, Chuang SE, 2016, Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells. RNA 22:303–315
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 421
EP 427
DI 10.1007/s12253-017-0366-4
PG 7
ER
PT J
AU Li, X
Wang, X
Xie, J
Liang, B
Wu, J
AF Li, Xiaohui
Wang, Xinjun
Xie, Jingwei
Liang, Bo
Wu, Jianheng
TI Suppression of Angiotensin-(1–7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ang-(1-7); Glioma; Blood-brain barrier; Claudin-5; ZO-1
ID Ang-(1-7); Glioma; Blood-brain barrier; Claudin-5; ZO-1
AB Glioblastoma multiforme (GBM) is the most primary brain tumor, specially characterized with the damage of blood-brain barrier (BBB). The Ang-(1–7) was proven to have an inhibitory effect on glioblastoma growth. However, its role on blood–brain barrier (BBB) and the underlying molecular mechanism remains unclear. In this study, Ang-(1–7) significantly relieved the damage of blood-brain barrier in rats with intracranial U87 gliomas as evaluated by magnetic resonance imaging (MRI). Furthermore, its treatment attenuated BBB permeability, tumor growth and edema formation. Similarly, Ang-(1–7) also decreased U87 glioma cells barrier permeability in vitro. Further analysis showed that Ang-(1–7) could effectively restore tight junction protein (claudin-5 and ZO-1) expression levels both in rats and U87 glioma cells by affecting the activation of JNK pathway. SP600125, an inhibitor of JNK, significantly enhanced the expression of Claudin-5 and ZO-1, and decreased the disruption of BBB and enhanced the efficiency of Ang-(1–7) in glioma rats. Taken together, this study demonstrated a protective role of Ang-(1–7) in glioma-induced blood-brain barrier damage by regulating tight junction protein expression. Accordingly, Ang-(1– 7) may become a promising therapeutic agent against glioma.
C1 [Li, Xiaohui] The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, No.3 Kangfuqian Street, Erqi District, 450052 Zhengzhou, China.
[Wang, Xinjun] The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, No.3 Kangfuqian Street, Erqi District, 450052 Zhengzhou, China.
[Xie, Jingwei] The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, No.3 Kangfuqian Street, Erqi District, 450052 Zhengzhou, China.
[Liang, Bo] The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, No.3 Kangfuqian Street, Erqi District, 450052 Zhengzhou, China.
[Wu, Jianheng] The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, No.3 Kangfuqian Street, Erqi District, 450052 Zhengzhou, China.
RP Wang, X (reprint author), The Fifth Affiliated Hospital of Zhengzhou University, Department of Neurosurgery, 450052 Zhengzhou, China.
EM wangjiang066@sina.com
CR Hawkins BT, Davis TP, 2005, The blood-brain barrier/ neurovascular unit in health and disease. Pharmacol Rev 57(2): 173–185
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 429
EP 435
DI 10.1007/s12253-018-0471-z
PG 7
ER
PT J
AU Langabeer, ES
Haslam, K
AF Langabeer, E Stephen
Haslam, Karl
TI Neutrophilia and the JAK2 V617F Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Langabeer, E Stephen] St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular DiagnosticsDublin, Ireland.
[Haslam, Karl] St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular DiagnosticsDublin, Ireland.
RP Langabeer, ES (reprint author), St. James’s Hospital, Central Pathology Laboratory, Cancer Molecular Diagnostics, Dublin, Ireland.
EM slangabeer@stjames.ie
CR Arber DA, Orazi A, Hasserjian R et al, 2016, The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405
Langabeer SE, 2012, Referral centre variation in requesting JAK2 V617F mutation analysis for the investigation of a myeloproliferative neoplasm. J Clin Pathol 65:1149–1150
Gong JZ, Cook JR, Greiner RC et al, 2013, Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report for the Association for Molecular Pathology. J Mol Diagn 15:733–744
Weir AB, Lewis JB Jr, Arteta-Bulos R, 2011, Chronic idiopathic neutrophilia: experience and recommendations. South Med J 104: 499–504
Ogunleye F, Ibrahim M, Allen E et al, 2016, BCR-ABL testing by polymerase chain reaction in patients with neutrophilia: the William Beaumont Hospital experience and the case for rational laboratory tests request. J Oncol Pract 12:e1001–e1005
Tefferi A, Noel P, Hanson CA, 2011, Uses and abuses of JAK2 and MPL mutation tests in myeloproliferative neoplasms. J Mol Diagn 13:461–466
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 437
EP 438
DI 10.1007/s12253-017-0315-2
PG 2
ER
PT J
AU Marton, I
Posfai,
Csomor, A
Vecsei, L
Borbenyi, Z
Sas, K
AF Marton, Imelda
Posfai, Eva
Csomor, Angela
Vecsei, Laszlo
Borbenyi, Zita
Sas, Katalin
TI Cerebrovascular Complications and Polycythaemia Vera
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Marton, Imelda] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Semmelweis 8Szeged, Hungary.
[Posfai, Eva] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Semmelweis 8Szeged, Hungary.
[Csomor, Angela] University of Szeged, Department of RadiologySzeged, Hungary.
[Vecsei, Laszlo] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Medical Faculty, Department of NeurologySzeged, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Semmelweis 8Szeged, Hungary.
[Sas, Katalin] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Medical Faculty, Department of NeurologySzeged, Hungary.
RP Marton, I (reprint author), University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Szeged, Hungary.
EM imeldamarton@gmail.com
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Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR, Cancer Genome P, 2005, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365(9464):1054–1061. , DOI 10.1016/S0140- 6736(05)71142-9
Teffe r i A, 2013, Polycythemia vera and essent i a l thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol 88(6):507–516. , DOI
1002/ajh.23417 10. Voko Z, Szeles G, Kardos L, Nemeth R, Adany R, 2008, The epidemiology of cerebrovascular diseases in Hungary after the millennium. LAM, Lege Artis Medicinae, 18(1):31–38
Adams BD, Baker R, Lopez JA, Spencer S, 2010, Myeloproliferative disorders and the hyperviscosity syndrome. Hematol Oncol Clin North Am 24(3):585–602. , DOI 10.1016/j.hoc.2010.03.004
Santisakultarm TP, Paduano CQ, Stokol T, Southard TL, Nishimura N, Skoda RC, Olbricht WL, Schafer AI, Silver RT, Schaffer CB, 2014, Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two-photon imaging. J Thromb Haemost. , DOI 10.1111/jth.1273
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2019
VL 25
IS 1
BP 439
EP 442
DI 10.1007/s12253-017-0329-9
PG 4
ER
PT J
AU Zhang, R
Zhang, J
Luo, W
Luo, Z
Shi, Sh
AF Zhang, Rui
Zhang, Jianwu
Luo, Wei
Luo, Zhuang
Shi, Shaoqing
TI WWP2 Is One Promising Novel Oncogene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE WWP2; Cancer; Akt; Pathogenesis
ID WWP2; Cancer; Akt; Pathogenesis
AB WWP2 is an E3 ubiquitin ligase and plays an important role in regulation of many cellular biological activities through ubiquitination and degradation of its substrates. Recently accumulating evidences indicate that WWP2 plays a crucial part in the pathogenesis in different types of tumors. In this report, the role of this gene especially in tumorigenesis was reviewed. WWP2 is dysregulated in various of tumors, and it promotes carcinogenesis mainly through PTEN/Akt signaling pathway. WWP2 also participates in anti-cancer agents’ sensitivity, indicating WWP2 may be a novel target for cancer treatment.WWP2 is one promising novel oncogene.
C1 [Zhang, Rui] The Seventh People’s Hospital of Chengdu, Department of Thoracic Surgery, 640021 Chengdu, Sichuan, China.
[Zhang, Jianwu] North Sichuan Medical College, School of Pharmacy, 637100 Nanchong, Sichuan, China.
[Luo, Wei] The People’s Hospital of Leshan, Department of Respiratory Medicine, 640000 Leshan, Sichuan, China.
[Luo, Zhuang] The First Affiliated Hospital of Kunming Medical University, Department of Pumnary and Critical Care Medicine, 650032 Kunming, Yunnan, China.
[Shi, Shaoqing] The First Affiliated Hospital of Kunming Medical University, Department of Pumnary and Critical Care Medicine, 650032 Kunming, Yunnan, China.
RP Luo, Z (reprint author), The First Affiliated Hospital of Kunming Medical University, Department of Pumnary and Critical Care Medicine, 650032 Kunming, China.
EM sky4511@126.com
CR Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CA, 2008, Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One 3:e1487
Bernassola F, Karin M, Ciechanover A, Melino G, 2008, The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell 14:10–21
Lu PJ, Zhou XZ, Shen M, Lu KP, 1999, Function ofWWdomains as phosphoserine- or phosphothreonine-binding modules. Science 283:1325–1328
Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM, 1997, Identification of novel human WW domain- containing proteins by cloning of ligand targets. J Biol Chem 272:14611–14616
Wood JD, Yuan J, Margolis RL, Colomer V, Duan K, Kushi J, Kaminsky Z, Kleiderlein JJ, Sharp AH, Ross CA, 1998, Atrophin-1, the DRPLA gene product, interacts with two families ofWWdomain-containing proteins.Mol CellNeurosci 11:149–160
Xu H,WangW, Li C, Yu H, Yang A,Wang B, Jin Y, 2009)WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res 19:561–573
Soond SM, Chantry A, 2011, Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFbeta signalling and EMT. Oncogene 30: 2451–2462
Liao B, Jin Y, 2010, Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner. Cell Res 20:332–344
Xu HM, Liao B, Zhang QJ, Wang BB, Li H, Zhong XM, Sheng HZ, Zhao YX, Zhao YM, Jin Y, 2004, Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. J Biol Chem 279:23495–23503
McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM, 2002, Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+, channel. Am J Physiol Renal Physiol 283:F431–F436
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Yang Y, Liao B, Wang S, Yan B, Jin Y, Shu HB, Wang YY, 2013, E3 ligase WWP2 negatively regulates TLR3-mediated innate immune response by targeting TRIF for ubiquitination and degradation. Proc Natl Acad Sci U S A 110:5115–5120
Lv Y, Zhang K, Gao H, 2014, Paip1, an effective stimulator of translation initiation, is targeted by WWP2 for ubiquitination and degradation. Mol Cell Biol 34:4513–4522
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Fukumoto C, Nakashima D, Kasamatsu A, Unozawa M, Shida- Sakazume T, Higo M, Ogawara K, Yokoe H, Shiiba M, Tanzawa H, Uzawa K, 2014)WWP2 is overexpressed in human oral cancer, determining tumor size and poor prognosis in patients: downregulation of WWP2 inhibits the AKT signaling and tumor growth in mice. Oncoscience 1:807–820
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Xu SQ, Qin Y, Pan DB, Ye GX, Wu CJ, Wang S, Jiang JY, Fu J, Wang CJ, 2016, Inhibition ofWWP2 suppresses proliferation, and induces G1 cell cycle arrest and apoptosis in liver cancer cells. Mol Med Rep 13:2261–2266
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Maddika S, Kavela S, Rani N, Palicharla VR, Pokorny JL, Sarkaria JN, Chen J, 2011, WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol 13:728–733
Qin Y, Xu SQ, Pan DB, Ye GX, Wu CJ, Wang S, Wang CJ, Jiang JY, Fu J, 2016, Silencing ofWWP2 inhibits adhesion, invasion, and migration in liver cancer cells. Tumour Biol 37:6787–6799
Yu Z, Li T,Wang C,Deng S, Zhang B, HuoX,WangX, ZhongY, Ma X, 2016, Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells. Oncotarget 7:15725–15737
Ding ZY, Huang YJ, Tang JD, Li G, Jiang PQ, Wu HT, 2016, Silencing of hypoxia-inducible factor-1alpha promotes thyroid cancer cell apoptosis and inhibits invasion by downregulatingWWP2, WWP9, VEGF and VEGFR2. Exp Ther Med 12:3735–3741
Wiesner S, Ogunjimi AA,Wang HR, Rotin D, Sicheri F,Wrana JL, Forman-Kay JD, 2007, Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell 130:651–662
Liu J,Wan L, Yuan Z, Zhang J, Guo J, Malumbres M, ZouW,Wei W, 2016, Cdh1 inhibits WWP2-mediated ubiquitination of PTEN to suppress tumorigenesis in an APC-independent manner. Cell discov 2:15044
Mund T, Graeb M, Mieszczanek J, Gammons M, Pelham HR, Bienz M, 2015, Disinhibition of the HECT E3 ubiquitin ligase WWP2 by polymerized Dishevelled. Open Biol 5:150185
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 443
EP 446
DI 10.1007/s12253-018-0506-5
PG 4
ER
PT J
AU Shree, H
Ramani, P
Sherlin, H
Sukumaran, G
Jeyaraj, G
Don, K
Santhanam, A
Ramasubramanian, A
Sundar, R
AF Shree, K. Hema
Ramani, Pratibha
Sherlin, Herald
Sukumaran, Gheena
Jeyaraj, Gifrrina
Don, R. Kanchi
Santhanam, Archana
Ramasubramanian, Abilasha
Sundar, R
TI Saliva as a Diagnostic Tool in Oral Squamous Cell Carcinoma – a Systematic Review with Meta Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE MMP-9; Chemerin; Saliva; Markers
ID MMP-9; Chemerin; Saliva; Markers
AB Whole saliva is mainly composed of fluid produced by major and minor salivary glands. Major salivary glands including parotid, submandibular, and sublingual glands, are known to secrete fluid transported from serum as well as surrounding glandular tissues [1]. Beside the secretions from salivary glands, oral mucosa, periodontium, as well as oral microflora also contribute to the final content of whole saliva [1]. Whole saliva therefore represents a complex balance among local and systemic sources [2]. This allows for the application of saliva in the diagnosis not only for salivary gland disorders but also for oral diseases and systemic conditions [2]. The role of saliva as a diagnostic tool in detecting Oral Squamous Cell Carcinoma. Articles published in PUBMED, EMBASE, COCHRANE, GOOGLE, manual search and back references of the articles for last 5 years extracted 77 articles. Studies which considered saliva as a diagnostic tool were included. Statistical analysis with Receivers Operating Curve to establish sensitivity and specificity of the salivary biomarkers as a diagnostic tool to detect Oral Squamous Cell Carcinoma were included for meta analysis. The measure of effect with 95% confidence interval were meta analysed for 9 articles in which 308 healthy individuals compared with 340 patients with Oral Squamous Cell Carcinoma. Highly sensitive salivary biomarkers for detecting Oral Squamous Cell Carcinoma were MMP-9, Chemerin, Choline + Betaine + Pipecolinic Acid + I – Carnitine(confidence interval ranges from 0.83–1.0). The narrow confidence interval of 0.95 + (0.88–1.00) was seen for MMP-9 followed by 1.00 + (0.78–1.00) for chemerin. Highly specific biomarkers for Oral Squamous Cell Carcinoma were MMP-9 (specificity −100%,), Chemerin(specificity-100%), over expressed mi RNA 136 with specificity of 0.88(0.69–0.97), under expressed mi RNA 27B with specificity of 1.0(0.66–1.00). Saliva can be used as a diagnostic tool with highly sensitive and specific markers namely MMP-9, Chemerin for early detection of Oral Squamous Cell Carcinoma.
C1 [Shree, K. Hema] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Ramani, Pratibha] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Sherlin, Herald] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Sukumaran, Gheena] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Jeyaraj, Gifrrina] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Don, R. Kanchi] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Santhanam, Archana] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Ramasubramanian, Abilasha] Saveetha Dental College, 162, Masilamani Nagar, Seneerkuppam bypass Road, Poonamallee, 600077 Chennai, Tamil Nadu, India.
[Sundar, R] Jamals Grandeur, Kauveri Nagar Main Road, Velappanchavadi, 600077 Chennai, Tamil Nadu, India.
RP Shree, H (reprint author), Saveetha Dental College, 600077 Chennai, India.
EM hemashree9111990@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 447
EP 453
DI 10.1007/s12253-019-00588-2
PG 7
ER
PT J
AU Tan, J
Jin, X
Wang, K
AF Tan, Jiufeng
Jin, Xuefei
Wang, Kaichen
TI Integrated Bioinformatics Analysis of Potential Biomarkers for Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Differentially expressed genes; Methylation; Network
ID Prostate cancer; Differentially expressed genes; Methylation; Network
AB The aim was to expound the pathogenesis of prostate cancer and to identify the potentially biomarkers for prostate cancer (PC). DNA methylation microarray data GSE38240 containing 8 prostate cancer metastases and 4 normal prostate samples as well as gene expression profile data GSE26910 containing 6 prostate primary tumors and 6 normal samples were used. Differentially expressed genes (DEGs) and differently methylated sites of PC were screened and the regulatory network was constructed with DEGs-related transcription factors (TFs). The obtained hub genes were subjected to proteinprotein interaction network analysis. Enrichment analysis of down-regulated DEGs were performed. Total 351 DEGs including 190 down-regulated and 161 upregulated genes and 3234 differently methylated sites were identified. In total 69 DEGs-related TFs were found. Regulatory network contained 1301 nodes and 2527 connection pairs and that FOXA1 (forkhead box A1), BZRAP1-AS1 (benzodiazapine receptor associated protein 1 antisense RNA 1) and KRT8 (keratin 8) were the top three nodes of it. The enriched GO terms were mainly biological activity of the blood and cells-related. Total 29 DEGs (such as AGTR1, angiotensin II receptor, type 1) and 57 none-DEGs involved in the PPI network. Biological functions in blood circulation and the involved AGTR1 may play important roles in PC by gene-methylation. Besides, BZRAP1-AS1 may be novel biomarker related with PC.
C1 [Tan, Jiufeng] China-Japan Union Hospital of Jilin University, Department of urology, 126 Xiantai ST, 130033 Changchun, Jilin Province, China.
[Jin, Xuefei] China-Japan Union Hospital of Jilin University, Department of urology, 126 Xiantai ST, 130033 Changchun, Jilin Province, China.
[Wang, Kaichen] China-Japan Union Hospital of Jilin University, Department of urology, 126 Xiantai ST, 130033 Changchun, Jilin Province, China.
RP Wang, K (reprint author), China-Japan Union Hospital of Jilin University, Department of urology, 130033 Changchun, China.
EM fyxehei@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 455
EP 460
DI 10.1007/s12253-017-0346-8
PG 6
ER
PT J
AU Laas, E
Ballester, M
Cortez, A
Graesslin, O
Darai, E
AF Laas, Enora
Ballester, Marcos
Cortez, Annie
Graesslin, Olivier
Darai, Emile
TI Unsupervised Clustering of Immunohistochemical Markers to Define High-Risk Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; High-risk endometrial cancer; Immunohistochemistry; Unsupervised clustering; Principal component analysis
ID Endometrial cancer; High-risk endometrial cancer; Immunohistochemistry; Unsupervised clustering; Principal component analysis
AB Considerable heterogeneity exists in outcomes of early endometrial cancer (EC) according to the type but also the histological grading. Our goal was to describe the immunohistochemical profiles of type I EC according to grades and type II EC, to identify groups of interacting proteins using principal component analysis (PCA) and unsupervised clustering. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins,metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms known for their role in endometrial pathology. Co-expressed proteins associated with the type, grade and outcome of EC were determined by PCA and unsupervised clustering. PCA identified three functional groups of proteins from 43 tissue samples (38 type I and 5 type II EC): the first was characterized by p53 expression; the second by MMPs, bcl-2, PR B and CD44v6; and the third by ER alpha, PR A, TIMP-2 and CD44v3. Unsupervised clustering found two main clusters of proteins, with both type I grade 3 and type II EC exhibiting the same cluster profile. PCA and unsupervised clustering of immunohistochemical markers in EC contribute to a better comprehension and classification of the disease.
C1 [Laas, Enora] AP-HP, Hopital Tenon, Service de Gynecologie-Obstetrique, 4 rue de la Chine, 75020 Paris, France.
[Ballester, Marcos] AP-HP, Hopital Tenon, Service de Gynecologie-Obstetrique, 4 rue de la Chine, 75020 Paris, France.
[Cortez, Annie] Universite Pierre et Marie Curie, Institut Universitaire de CancerologieParis, France.
[Graesslin, Olivier] CHU de Reims, Hopital Alix de Champagne, Service de gynecologie-obstetrique, 45 rue Cognacq-Jay, 51100 Reims, France.
[Darai, Emile] AP-HP, Hopital Tenon, Service de Gynecologie-Obstetrique, 4 rue de la Chine, 75020 Paris, France.
RP Laas, E (reprint author), AP-HP, Hopital Tenon, Service de Gynecologie-Obstetrique, 75020 Paris, France.
EM enora.laas@curie.fr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 461
EP 469
DI 10.1007/s12253-017-0335-y
PG 9
ER
PT J
AU Trabzonlu, L
Muezzinoglu, B
Corakci, A
AF Trabzonlu, Levent
Muezzinoglu, Bahar
Corakci, Aydin
TI BCL-2 and PAX2 Expressions in EIN which Had Been Previously Diagnosed as Non-Atypical Hyperplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial intraepithelial neoplasia; PAX2; BCL-2; Immunohistochemistry; Uterus; Endometrial hyperplasia
ID Endometrial intraepithelial neoplasia; PAX2; BCL-2; Immunohistochemistry; Uterus; Endometrial hyperplasia
AB The relationship between PAX2 and another anti-apoptotic gene, BCL-2, has been shown in a limited number of studies. The aims of this study are to investigate the value of PAX2 and BCL-2 expressions in lesions which have been defined as nonatypical hyperplasia in terms of detecting EIN and to evaluate the relations of these proteins in EIN. For this purpose, 108 cases of nonatypical endometrial hyperplasia diagnosed from 2006 to 2011 were re-evaluated. Immunohistochemical studies with PAX2 and BCL-2 were performed in 20 cases with EIN and 34 cases with benign hyperplasia. The mean BCL-2 immunohistochemistry scores of benign hyperplasia and EIN cases were 4.06 ± 1.04 and 4.63 ± 2.03, respectively. The mean BCL-2 score of EIN cases was significantly higher than benign hyperplasia (p = 0.021). The mean PAX2 scores of benign hyperplasia and EIN cases were 4.32 ± 1.07 and 2.19 ± 2.34, respectively. The mean PAX2 scores of EIN cases were significantly lower than benign hyperplasia (p = 0.001). BCL-2 expression was increased compared to normal endometrium in 66.7% of EIN cases, and PAX2 expression was decreased in 73.3%. Consistent with this, in 60% of cases, BCL-2 expression was increased compared to normal endometrium, while PAX2 expression was decreased. BCL-2 and PAX2 protein expression changes occur in early phases of endometrial tumorigenesis. These changes are often seen as a simultaneous increase in BCL-2 expression and decrease in PAX2 expression.
C1 [Trabzonlu, Levent] Johns Hopkins School of Medicine, Department of Pathology, 600 N Wolfe Street, 21287 Baltimore, MD, USA.
[Muezzinoglu, Bahar] Kocaeli University School of Medicine, Department of PathologyKocaeli, Turkey.
[Corakci, Aydin] Kocaeli University School of Medicine, Department of Gynecology and ObstetricsKocaeli, Turkey.
RP Trabzonlu, L (reprint author), Johns Hopkins School of Medicine, Department of Pathology, 21287 Baltimore, USA.
EM leventtrabzonlu186@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 471
EP 476
DI 10.1007/s12253-017-0378-0
PG 6
ER
PT J
AU Szekerczes, T
Galamb,
Kocsis, A
Benczik, M
Takacs, T
Martonos, A
Jaray, B
Kiss, A
Jeney, Cs
Nyiri, M
Schaff, Zs
Sobel, G
AF Szekerczes, Timea
Galamb, Adam
Kocsis, Adrienn
Benczik, Marta
Takacs, Tibor
Martonos, Attila
Jaray, Balazs
Kiss, Andras
Jeney, Csaba
Nyiri, Miklos
Schaff, Zsuzsa
Sobel, Gabor
TI Dual-Stained Cervical Cytology and Histology with Claudin-1 and Ki67
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Claudin-1/Ki67 immunochemistry; p16/Ki67 reaction; Claudins
ID Cervical cancer; Claudin-1/Ki67 immunochemistry; p16/Ki67 reaction; Claudins
AB Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/ Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.
C1 [Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Galamb, Adam] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Kocsis, Adrienn] CellCall LtdBudapest, Hungary.
[Benczik, Marta] CellCall LtdBudapest, Hungary.
[Takacs, Tibor] CellCall LtdBudapest, Hungary.
[Martonos, Attila] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Jeney, Csaba] CellCall LtdBudapest, Hungary.
[Nyiri, Miklos] CellCall LtdBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Sobel, Gabor] Semmelweis University, 2nd Department of Obstetrics and GynecologyBudapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff.zsuzsa@med.semmelweis-univ.hu
CR Hillemans P, Soergel P, Hertel H, Jentschke M, 2016, Epidemiology and early detection of cervical cancer. Oncol Res Treat 39:1–6
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Lees BF, Erickson BK, Huh WK(2016, Cervical cancer screening: evidence behind the guidelines.AmJ Obstet Gynecol 214:438–443
Ocque R, Austin RM, 2016, Follow-up of women with negative pap test results and abnormal clinical signs or symptoms. Am J Clin Pathol 145:560–567
Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, Keller T, von Knebel Doeberitz M, Neumann HH, Puig-Tintore LM, Sideri M, Rehm S, Ridder R, PALMS Study Group, 2013, Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst 105:1550–1557
Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, Tokugawa D, Bodelon C, Roitras N, Lorey T, Kinney W, 2015, p16/Ki-67 dual stain cytology for detection of cervical precancer in HPV-positive women. J Natl Cancer Inst 107: 1–8
Cuzick J, Clavel C, Petry KU, Meijer CJ, Hoyer H, Ratnam S, Szarewski A, Birembaut P, Kulasingam S, Sasieni P, Iftner T, 2006, Overview of the European and north American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119: 1095–1101
PlummerM, Schiffman M, Castle PE,Maucort-Boulch D,Wheeler CM, ALTS Group, 2007, A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 195:1582– 1589
Benczik M, Galamb A, Koiss R, Kovacs A, Jaray B, Szekely T, Szekerczes T, Schaff Z, Sobel G, Jeney C, 2016, Claudin-1 as a biomarker of cervical cytology and histology. Pathol Oncol Res 22: 179–188
Bergeron C, Ikenberg H, SideriM, Denton K, Bogers J, Schmidt D, Alameda F, Keller T, Rehm S, Ridder R, PALMS Study Group, 2015, Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results. Cancer Cytopathol 123:373–381
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Sobel G, Paska C, Szabo I, Kiss A, Kadar A, Schaff Z, 2005, Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma. Hum Pathol 36: 162–169
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Solomon D, 2015, Foreword. In: Nayar F, Wilbur DC, ed, The Bethesda system for reporting cervical cytology. Definitions, criteria, and explanatory notes, 3rd ed. Springer International Publishing Switzerland, Cham, pp v-vii
Wentzensen N, von Knebel Doeberitz M, 2007, Biomarkers in cervical cancer screening. Dis Markers 23:315–330
Lee S, Rose MS, Sahasrabuddhe VV, Zhao R, Duggan MA, 2017, Tissue-based immunohistochemical biomarker accuracy in the diagnosis of malignant glandular lesions of the uterine cervix: a systematic review of the literature and meta-analysis. Int J Gynecol Pathol 36:310–322
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Akimoto T, Takasawa A, Murata M, Kojima Y, Takasawa K, Nojima M, Aoyama T, Hiratsuka Y, Ono Y, Tanaka S, Osanai M, Hasegawa T, Saito T, Sawada N, 2016, Analysis of the expression and localization of tight junction transmembrane proteins, claudin- 1, −4, −7, occludin and JAM-A, in human cervical adenocarcinoma. Histol Histopathol 31:921–931
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 477
EP 486
DI 10.1007/s12253-018-0384-x
PG 10
ER
PT J
AU Kallay, K
Zakarias, D
Csordas, K
Benyo, G
Kassa, Cs
Sinko, J
Strehn, A
Horvath, O
Vasarhelyi, B
Krivan, G
AF Kallay, Krisztian
Zakarias, David
Csordas, Katalin
Benyo, Gabor
Kassa, Csaba
Sinko, Janos
Strehn, Anita
Horvath, Orsolya
Vasarhelyi, Barna
Krivan, Gergely
TI Antithymocyte Globuline Therapy and Bradycardia in Children
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Antithymocyte globulin; ATG; Bradycardia; Children
ID Antithymocyte globulin; ATG; Bradycardia; Children
AB In antithymocyte globulin (ATG) treated patients occasionally bradycardia has been noticed. Therefore, we retrospectively analyzed the occurrence of bradycardia in ATG-treated children. Usingmedical records between 2007 and 2012 we identified children undergoing a combined therapy with ATG and glucocorticoids (ATG group, n = 22). The incidence of bradycardia was compared to that registered in children treated with glucocorticoids alone (glucocorticoid alone group, n = 21). Heart rates (HR) were registered before and on days 0–3, 4–7 and 8–14 after the ATG or steroid administration. The rate of bradycardic episodes was higher during ATG therapy than in the steroid alone group, while severe bradycardia occurred only in the ATG group (97 versus 32, p = 0.0037, and 13 versus 0, p = 0.0029, respectively). There was an interaction between the time and treatment group on HR (p = 0.046). Heart rates in ATG and steroid alone groups differed significantly on day 0–3 and day 4–7 (p = 0.046, p = 0.006, respectively).Within the ATG group HR was lower on days 4–7 compared to the days before and the days 8–14 values (p < 0.001, 95% CI: 0.020–0.074). These findings indicate that transient asymptomatic bradycardia is probably more common with ATG therapy than previously reported. HR should be closely monitored during and after ATG therapy.
C1 [Kallay, Krisztian] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Zakarias, David] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Csordas, Katalin] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Benyo, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Kassa, Csaba] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Sinko, Janos] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Strehn, Anita] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Horvath, Orsolya] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
[Vasarhelyi, Barna] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Krivan, Gergely] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Albert Florian street 5-7, H-1097 Budapest, Hungary.
RP Kallay, K (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, H-1097 Budapest, Hungary.
EM dr.kallay@gmail.com
CR George B, Mathews V, Viswabandya A, Lakshmi KM, Srivastava A, ChandyM(2010, Allogeneic hematopoietic stem cell transplantation is superior to immunosuppressive therapy in Indian children with aplastic anemia–a single-center analysis of 100 patients. Pediatr Hematol Oncol 27(2):122–131
Karapinar DY, Karadas N, Ay Y, Akin M, Balkan C, Aydinok Y, Kavakli K, 2014, Rabbit antithymocyte globulin treatment in childhood acquired severe aplastic anemia. Pediatr Hematol Oncol 31(1):20–28
Jiang S, Wang Y, Shi W, Shao Y, Qiao X, Lin J, Kuang H, Xie X, 2009, The benefit of ATG in immunosuppressive therapy of children with moderate aplastic anemia. Pediatr Hematol Oncol 26(5): 313–320
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Scheinberg P, Townsley D, Dumitriu B, Scheinberg P,Weinstein B, Rios O,Wu CO,Young NS, 2014, Horse antithymocyte globulin as salvage therapy after rabbit antithymocyte globulin for severe aplastic anemia. Am J Hematol 89(5):467–469
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, 2011)Wu CO, et al. horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 365(5):430–438
Godown J, Deal AM, Riley K, Bailliard F, Blatt J, 2011)Worsening bradycardia following antithymocyte globulin treatment of severe aplastic anemia. J Pediatr Pharmacol Ther 16(3):218–221
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Costedoat-Chalumeau N, Amoura Z, Villain E, Cohen L, Piette JC, 2005, Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block? A review of electrocardiographic and myocardial abnormalities and of treatment options. Arthritis Research& Therapy 7(2):69–73
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van der Gugten A, Bierings M, Frenkel J, 2008, Glucocorticoidassociated bradycardia. J Pediatr Hematol Oncol 30(2):172–175
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 487
EP 492
DI 10.1007/s12253-018-0403-y
PG 6
ER
PT J
AU Blancas, S
Medina-Berlanga, R
Ortiz-Garcia, L
Loredo-Ramirez, A
Santos, L
AF Blancas, Sugela
Medina-Berlanga, Rogelio
Ortiz-Garcia, Liliana
Loredo-Ramirez, Alfredo
Santos, Leticia
TI Protein Expression Analysis in Uterine Cervical Cancer for Potential Targets in Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine cervical cancer; SEL1L; Notch3; SOCS3; Immunohistochemistry; Tissue microarray
ID Uterine cervical cancer; SEL1L; Notch3; SOCS3; Immunohistochemistry; Tissue microarray
AB Specific markers in lesions of the human uterine cervix cancer (UCC) are still needed for prognostic, diagnostic and/or therapeutic purposes. In this study we evaluated key molecules at protein level between normal epithelium, cervical intraepithelial neoplasia (CIN1–3) and invasive cancer of a group of molecules previously reported at mRNA level. For that purpose, human formalin-fixed paraffin embedded tissue microarrays (TMAs) were constructed containing 205 Mexican tissue core specimens. Immunohistochemistry and quantitative analysis of histological staining was performed against twenty-two distinct proteins for each core and the processing platform ImageJ. In the progression of the disease we found key statistical differences for the proteins SEL1, Notch3 and SOCS3. High expressions of SEL1L, Notch3 and SOCS3 have potential value to increase the prognostic of UCC in combination with markers such as p16INK4a. This study identified key drivers in cervical carcinogenesis that should be evaluated for the development of UCC therapies.
C1 [Blancas, Sugela] A.C. (IPICYT), Instituto Potosino de Investigacion Cientifica y Tecnologica, Division de Biologia MolecularSan Luis Potosi, Mexico.
[Medina-Berlanga, Rogelio] A.C. (IPICYT), Instituto Potosino de Investigacion Cientifica y Tecnologica, Division de Biologia MolecularSan Luis Potosi, Mexico.
[Ortiz-Garcia, Liliana] Universidad Politecnica de Penjamo, Facultad de Ingenieria en Biotecnologia, PenjamoGuanajuato, Mexico.
[Loredo-Ramirez, Alfredo] Laboratorio de Patologia Quirurgica, Mariano Arista 743, Interior 208San Luis Potosi, Mexico.
[Santos, Leticia] A.C. (IPICYT), Instituto Potosino de Investigacion Cientifica y Tecnologica, Division de Biologia MolecularSan Luis Potosi, Mexico.
RP Santos, L (reprint author), A.C. (IPICYT), Instituto Potosino de Investigacion Cientifica y Tecnologica, Division de Biologia Molecular, San Luis Potosi, Mexico.
EM lsantos@ipicyt.edu.mx
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Palermo R, Checquolo S, Bellavia D, Talora C, Screpanti I, 2014, The molecular basis of notch signaling regulation: a complex simplicity. Curr Mol Med 14(1):34–44
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Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, Keller T, von Knebel Doeberitz M, Neumann HH, Puig-Tintore LM, Sideri M, Rehm S, Ridder R, Group PS, 2013, Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst 105(20):1550–1557. https:// doi.org/10.1093/jnci/djt235
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 493
EP 501
DI 10.1007/s12253-018-0401-0
PG 9
ER
PT J
AU Singh, L
Saini, N
Pushker, N
Bakhshi, S
Sen, S
Nag, CT
Kashyap, S
AF Singh, Lata
Saini, Neeru
Pushker, Neelam
Bakhshi, Sameer
Sen, Seema
Nag, C Tapas
Kashyap, Seema
TI Mutational Analysis of the Mitochondrial DNA Displacement-Loop Region in Human Retinoblastoma with Patient Outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Retinoblastoma; D-loop; Mitochondrial DNA; DNA sequencing; Electron microscopy
ID Retinoblastoma; D-loop; Mitochondrial DNA; DNA sequencing; Electron microscopy
AB Alteration in mitochondrial DNA plays an important role in the development and progression of cancer. The Displacement Loop (Dloop) region of mitochondrial DNA (mtDNA) is the regulatory region for its replication and transcription. Therefore, we aimed to characterize mutations in the D-loop region of mitochondrial DNA along with themorphological changes and analyzed their impact on survival in retinoblastoma patients. mtDNA D-loop region was amplified by Nested-Polymerase Chain Reaction (Nested-PCR) and mutations were analyzed in 60 tumor samples from retinoblastoma patients by DNA sequencing. Transmission electron microscopy was performed on 5 retinoblastoma specimens. Mutations were correlated with clinical, histopathological parameters and patient survival. D-loop mutations were found in total of 52/60 (86.6%) patients. The most common mutations were T to C and C to T followed by A to G. There were 5.81% mutations which were not previously reported in the MITOMAP database. A73G (83.33%) were the most frequent mutations found in our cases and it was statistically significant with poor tumor differentiation and age. In addition, this study was further analyzed formorphological changes in retinoblastoma that had disorganized, swollen and less numbers of mitochondria on electron microscopy. This is the first study showing high frequency of mtDNA mutation which might be due to abnormal morphology of mitochondria in retinoblastoma. Our results indicate that pathogenic mtDNA D-loop mutations may be involved in tumorigenesis of retinoblastoma tumor.
C1 [Singh, Lata] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Saini, Neeru] Institute of Genomics and Integrative Biology, Functional Genomics UnitNew Delhi, India.
[Pushker, Neelam] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of OphthalmologyNew Delhi, India.
[Bakhshi, Sameer] All India Institute of Medical Sciences, IRCH, Department of Medical OncologyNew Delhi, India.
[Sen, Seema] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
[Nag, C Tapas] All India Institute of Medical Sciences, Department of AnatomyNew Delhi, India.
[Kashyap, Seema] All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular PathologyNew Delhi, India.
RP Singh, L (reprint author), All India Institute of Medical Sciences, Dr. R. P. Centre for Ophthalmic Sciences, Department of Ocular Pathology, New Delhi, India.
EM lata.aiims@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 503
EP 512
DI 10.1007/s12253-018-0391-y
PG 10
ER
PT J
AU Inno, A
Di Noia, V
Martini, M
D’Argento, E
Di Salvatore, M
Arena, V
Schinzari, G
Orlandi, A
Larocca, ML
Cassano, A
Barone, C
AF Inno, Alessandro
Di Noia, Vincenzo
Martini, Maurizio
D’Argento, Ettore
Di Salvatore, Mariantonietta
Arena, Vincenzo
Schinzari, Giovanni
Orlandi, Armando
Larocca, Maria Luigi
Cassano, Alessandra
Barone, Carlo
TI Erlotinib for Patients with EGFR Wild-Type Metastatic NSCLC: a Retrospective Biomarkers Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR wild-type; NSCLC; Erlotinib; K-RAS mutation; IGF1-R expression; C-MET expression
ID EGFR wild-type; NSCLC; Erlotinib; K-RAS mutation; IGF1-R expression; C-MET expression
AB Erlotinib is approved for the treatment of patients with EGFR mutation positive, metastatic NSCLC. It is also approved as second/ third line therapy for EGFR mutation negative patients, but in this setting the benefit of erlotinib is modest and there is no validated biomarker for selecting EGFR wild-type patients who may benefit the most from the treatment. We retrospectively assessed EGFR and K-RAS mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012. We analyzed the association between biomarkers and outcome (RR, PFS, and OS). EGFR mutated patients achieved a better RR (56% vs 8%, p = .002), PFS (10 vs 3 months, HR 0.53, p = 0.48) and OS (20 vs 6 months, HR 0.55, p = .07), compared to EGFR wild-type patients. Among 63 EGFR wild-type patients, those with EGFR high-expression had a better outcome in terms of RR (40% vs 2%, p = .002), PFS (7.5 vs 2 months, HR 0.45, p = .007) and OS (30 vs 5 months, HR 0.34, p < .001) compared to patients with EGFR intermediate or low/negative-expression. IGF1-R expression, c-MET expression and K-RAS mutational status did not significantly affect the outcome; however, no patients with K-RAS mutation or c-MET high-expression achieved an objective response. In patients with metastatic, chemo-refractory EGFR wild-type NSCLC, EGFR high-expression may represent a positive predictor of activity for erlotinib, whereas K-RAS mutation and c-MET high-expression may predict lack of activity. These findings deserve further prospective evaluation.
C1 [Inno, Alessandro] Ospedale Sacro Cuore Don Calabria, Cancer Care Center, Medical Oncology Unit, Via don A. Sempreboni 5, 37024 Negrar, Verona, Italy.
[Di Noia, Vincenzo] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Martini, Maurizio] Universita Cattolica del Sacro Cuore, Department of PathologyRome, Italy.
[D’Argento, Ettore] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Di Salvatore, Mariantonietta] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Arena, Vincenzo] Universita Cattolica del Sacro Cuore, Department of PathologyRome, Italy.
[Schinzari, Giovanni] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Orlandi, Armando] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Larocca, Maria Luigi] Universita Cattolica del Sacro Cuore, Department of PathologyRome, Italy.
[Cassano, Alessandra] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
[Barone, Carlo] Universita Cattolica del Sacro Cuore, Department of Medical OncologyRome, Italy.
RP Inno, A (reprint author), Ospedale Sacro Cuore Don Calabria, Cancer Care Center, Medical Oncology Unit, 37024 Negrar, Italy.
EM alessandro.inno@sacrocuore.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 513
EP 520
DI 10.1007/s12253-018-0404-x
PG 8
ER
PT J
AU Zalatnai, A
Galambos, E
Perjesi, E
AF Zalatnai, Attila
Galambos, Eszter
Perjesi, Eszter
TI Importance of Immunohistochemical Detection of Somatostatin Receptors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroendocrine tumors; Immunohistochemistry; Somatostatin receptors
ID Neuroendocrine tumors; Immunohistochemistry; Somatostatin receptors
AB The long-acting somatostatin analogs represent important weapons in treatment protocols of patients with neuroendocrine tumors. Because these peptides preferentially bind to the specific somatostatin receptors, the targeted therapy requires detection of them. As one of the national consulting centers, here we present the results of the immunohistochemically positive neuroendocrine neoplasms diagnosed between 2010 and 2014. Twenty-four paraffin-embedded cases (14 females 10 men, 21–79 years) from different localizations were found to express somatostatin-receptor type 2 (SSTR2). None of the patients has received previous hormonal therapy. The immune reactions have shown membranous, cytoplasmic or mixed patterns. There was no correlation between the expression and the chromogranin A levels, the grades or the hormonal activity/inactivity of the given neoplasms. Our results show that the immunohistochemical detection of SSTR2 is a quick, reliable and effective tool that provides useful information to the oncologists for the therapeutic decision. Because the incidence of the neuroendocrine tumors is still low, centralized pathological units are needed to perform such technique.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26,, H-1085 Budapest, Hungary.
[Galambos, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26,, H-1085 Budapest, Hungary.
[Perjesi, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26,, H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
CR Pollak MN, Schally AV, 1998, Mechanisms of antineoplastic action of somatostatin analogs. Proc Soc Exp BiolMed 217:143–152
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 521
EP 525
DI 10.1007/s12253-018-0426-4
PG 5
ER
PT J
AU Wang, L
Aireti, A
Aihaiti, A
Li, K
AF Wang, Lei
Aireti, Ailixiati
Aihaiti, Aizezi
Li, Kun
TI Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and their Clinical Implications
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; microRNA-150; Insulin-like growth factor 2 mRNA-binding protein 1; Clinicopathological feature; Overall survival; Disease-free survival
ID Osteosarcoma; microRNA-150; Insulin-like growth factor 2 mRNA-binding protein 1; Clinicopathological feature; Overall survival; Disease-free survival
AB Previous study revealed that microRNA (miR)-150 might function as a tumor suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in 20 osteosarcoma and matched adjacent noncancerous tissues were respectively detected by quantitative real-time PCR and western blot analyses. Then, subcellular localization and expression pattern of IGF2BP1 protein in 100 osteosarcoma tissues were examined by immunohistochemistry. Associations of miR-150/IGF2BP1 expression with various clinicopathological features and patients’ prognosis were also statistically evaluated. As a result, miR-150 expression was significantly decreased, while IGF2BP1 mRNA and protein expressionwere dramatically increased in osteosarcoma tissues compared to matched adjacent noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all significantly associated with high tumor grade, presence of metastasis and recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover, miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as independent prognostic factors for overall and disease-free survivals of osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR-150 and its downstream target IGF2BP1 may be a crucial axis for the development, progression and patients’ prognosis of ostesarcoma. The newly identified miR-150/IGF2BP1 axismight be a novel potential therapeutic target for osteosarcoma treatment.
C1 [Wang, Lei] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Orthopedics Center Spine Surgery, 830000 Urumqi, China.
[Aireti, Ailixiati] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Orthopedics Center Spine Surgery, 830000 Urumqi, China.
[Aihaiti, Aizezi] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Orthopedics Center Spine Surgery, 830000 Urumqi, China.
[Li, Kun] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Orthopedics Center Spine Surgery, 830000 Urumqi, China.
RP Wang, L (reprint author), People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Orthopedics Center Spine Surgery, 830000 Urumqi, China.
EM wanglei20170311@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 527
EP 533
DI 10.1007/s12253-018-0454-0
PG 7
ER
PT J
AU Szasz, R
Altai, E
Pal, K
Dombi, P
Ivanyi, J
Jakucs, J
Joni, N
Illes,
Tarkanyi, I
Szerafin, L
Nagy, Zs
Farkas, P
Nagy,
Piukovics, K
Ujj, Gy
Schneider, T
AF Szasz, Robert
Altai, Elvira
Pal, Katalin
Dombi, Peter
Ivanyi, Janos
Jakucs, Janos
Joni, Natalia
Illes, Arpad
Tarkanyi, Ilona
Szerafin, Laszlo
Nagy, Zsolt
Farkas, Peter
Nagy, Agnes
Piukovics, Klara
Ujj, Gyorgy
Schneider, Tamas
TI Effectiveness of the Combination of Rituximab and Standard Chemotherapeutic Regimens in Previously Untreated Patients with Chronic Lymphocytic Leukaemia in Real-Life: Results from a Noninterventional Study (CILI Study)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chronic lymphocytic leukemia; Rituximab; Overall response rate
ID Chronic lymphocytic leukemia; Rituximab; Overall response rate
AB Chronic lymphocytic leukemia (CLL) is one of the most common haematological malignancies exhibiting remarkable heterogeneity in clinical course. Rituximab added to standard chemotherapy has been proven to increase response rate and eventually survival among previously untreated CLL patients. CILI was an open-label, non-randomized, single arm, multicentric, observational study aimed to collect real-life effectiveness data for rituximab used according to the current label in combination with standard chemotherapy in previously untreated CLL patients. Overall response rates (ORR) in the entire study population as well as in various subgroups were estimated. Adverse events were recorded during the entire course of the study. A total number of 150 patients were enrolled by 15 Hungarian study sites. Out of these, 82 patients received 6 cycles of rituximab containing treatment. Overall response rates of 88.24% (CI95%: 81.6–93.12%) and 94.59% (CI95%: 86.73–98.51%) were recorded in the intent-to-treat (ITT) and per-protocol (PP) populations, respectively. In both study populations, somewhat higher ORR was observed in patients aged ≥65 years. Subgroups defined according to either chromosomal aberrations (presence of 11q and 17p deletions) showed apparently high ORRs, though these rates were most probably biased by low patient numbers. 144 adverse events were reported during the study, of which 15 AEs were considered to be related to the administration of rituximab. Analyses of the efficacy variables have revealed comparable results to those previously reported by controlled clinical trials.
C1 [Szasz, Robert] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Altai, Elvira] Veszprem County Csolnoky Ferenc Hospital, Korhaz u. 1, 8200 Veszprem, Hungary.
[Pal, Katalin] Fejer County Szent Gyorgy Hospital, Seregelyesi ut 3, 8000 Szekesfehervar, Hungary.
[Dombi, Peter] Szent Borbala Hospital, Department of Hematology, Dozsa Gyorgy ut 77, 2800 Tatabanya, Hungary.
[Ivanyi, Janos] Vas County Markusovszky Hospital, Department of Hematology, Markusovszky L. u. 5, 9700 Szombathely, Hungary.
[Jakucs, Janos] Bekes County Pandy Kalman Hospital, Department of Internal Medicine, Semmelweis u. 1, 5700 Gyula, Hungary.
[Joni, Natalia] Ferenc Markhot County Hospital, Szechenyi u. 27-29, 3300 Eger, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Tarkanyi, Ilona] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor u. 2/A, 1083 Budapest, Hungary.
[Szerafin, Laszlo] Szabolcs-Szatmar-Bereg County Josa Andras Hospital, Department of Haematology, Szent Istvan u. 68, 4400 Nyiregyhaza, Hungary.
[Nagy, Zsolt] Borsod-Abauj-Zemplen County Hospital, 2nd Department of Internal Medicine, Csabai kapu 9-11, 3529 Miskolc, Hungary.
[Farkas, Peter] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, 1125 Budapest, Hungary.
[Nagy, Agnes] University of Pecs, I. Department of Internal Medicine, Ifjusag ut 13, 7624 Pecs, Hungary.
[Piukovics, Klara] University of Szeged, 2nd Department of Internal Medicine and Cardiology Centre, Koranyi Fasor 6, 6720 Szeged, Hungary.
[Ujj, Gyorgy] Jasz-Nagykun-Szolnok County Hetenyi Geza Hospital, I. Department of Internal Medicine, Toszegi ut 21, 5004 Szolnok, Hungary.
[Schneider, Tamas] National Institute of Oncology, Rath Gyorgy u. 7-9, 1122 Budapest, Hungary.
RP Szasz, R (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, 4032 Debrecen, Hungary.
EM szaszr@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 535
EP 540
DI 10.1007/s12253-018-0474-9
PG 6
ER
PT J
AU Niu, Y
Yang, X
Chen, Y
Zhang, L
Jin, X
Tang, Y
Li, L
Yu, L
Guo, Y
Wang, H
AF Niu, Yuna
Yang, Xue
Chen, Yifei
Zhang, Linbo
Jin, Xinyue
Tang, Youjing
Li, Li
Yu, Lu
Guo, Yilin
Wang, Hui
TI BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BCL3; Expression; Prognosis; Acute myeloid leukemia
ID BCL3; Expression; Prognosis; Acute myeloid leukemia
AB Although the implication of BCL3 has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic of BCL3 expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detect BCL3 expression level. BCL3 mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls (P = 0.0015). BCL3 was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes (P = 0.014). ROC analysis demonstrated that BCL3 could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of low BCL3 expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 (P = 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 (P = 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed that BCL3low patients had a remarkably higher frequency of t (8;21) abnormality (P = 0.0047) and lower frequency of normal karyotype (P = 0.0059) than BCL3high patients. BCL3high patients showed a significantly higher frequency of FLT3-ITD mutation (P = 0.028) and lower frequency of C-Kit mutation (P = 0.0232) than BCL3low patients. Although there were no significant differences in complete remission and overall survival between BCL3low and BCL3high groups, patients with high BCL3 expression markedly shorter overall survival (OS, P = 0.049), relapse-free survival (RFS, P = 0.027) and disease-free survival (DFS, P = 0.042) in M2AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate (P = 0.0317) after the second induction treatment than patientswith BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.
C1 [Niu, Yuna] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Yang, Xue] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Chen, Yifei] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Zhang, Linbo] Xinxiang Medical University, the Third Affiliated Hospital, Department of Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Jin, Xinyue] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Tang, Youjing] Xinxiang Medical University, the First Affiliated Hospital, Laboratory of HematologyWeihui, Henan, China.
[Li, Li] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Yu, Lu] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Guo, Yilin] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
[Wang, Hui] Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, Henan, China.
RP Wang, H (reprint author), Xinxiang Medical University, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, 453003 Xinxiang, China.
EM huiwang65@yeah.net
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 541
EP 548
DI 10.1007/s12253-018-0476-7
PG 8
ER
PT J
AU Koeneman, MM
Ovestad, TI
Janssen, AME
Ummelen, M
Kruitwagen, FPMR
Hopman, HA
Kruse, JA
AF Koeneman, M Margot
Ovestad, T Irene
Janssen, A M Emiel
Ummelen, Monique
Kruitwagen, F P M Roy
Hopman, H Anton
Kruse, J Arnold
TI Gain of Chromosomal Region 3q26 as a Prognostic Biomarker for High-Grade Cervical Intraepithelial Neoplasia: Literature Overview and Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hTERC; 3q26; Cervical intraepithelal neoplasia; Prognosis; Biomarker
ID hTERC; 3q26; Cervical intraepithelal neoplasia; Prognosis; Biomarker
AB Approximately 20–40% of high-grade Cervical Intraepithelial Neoplasia (CIN) regresses spontaneously, but the natural prognosis of an individual lesion is unpredictable. Gain of the chromosomal 3q region, which contains the human telomerase RNA gene on 3q26, is found in CIN lesions and cervical carcinoma and shows correlation with disease grade. The aim of this study is to assess whether 3q26 gain as a single genetic marker can predict the natural prognosis of highgrade CIN, by performing a review of the literature and pilot study. A literature review was conducted. Additionally, we performed a pilot study in 19 patients with histologically confirmed high-grade CIN lesions who were followed for a mean of 115 days, after which loop excision was performed. Fluorescent in situ hybridization analysis was performed on the initial diagnostic biopsies to determine gain of 3q26. Eight studies were included in the literature overview, with a total of 407 patients. Of these, only 22 patients had high-grade lesions. All studies found an association between 3q26 gain and disease prognosis. Positive predictive values (PPV) ranged from 50 to 93%, negative predictive values (NPV) ranged from 75 to 100%. Only five out of 155 patients (3.2%) without 3q26 gain showed disease persistence or progression. In our pilot study on 3q26 gain in high-grade CIN, the PPV of 3q26 gain for disease persistence was 67%, the NPV 100%. All four patients without 3q26 gain showed disease regression. In conclusion, the absence of 3q26 gain in diagnostic biopsies may be applied to identify high-grade CIN lesions with a high probability of disease regression.
C1 [Koeneman, M Margot] Maastricht University, Medical Centre, Department of Obstetrics and GynecologyMaastricht, The Netherlands.
[Ovestad, T Irene] Stavanger University Hospital, Department of PathologyStavanger, Norway.
[Janssen, A M Emiel] Stavanger University Hospital, Department of PathologyStavanger, Norway.
[Ummelen, Monique] Maastricht University, GROW - School for Oncology and Developmental BiologyMaastricht, The Netherlands.
[Kruitwagen, F P M Roy] Maastricht University, Medical Centre, Department of Obstetrics and GynecologyMaastricht, The Netherlands.
[Hopman, H Anton] Maastricht University, GROW - School for Oncology and Developmental BiologyMaastricht, The Netherlands.
[Kruse, J Arnold] Maastricht University, Medical Centre, Department of Obstetrics and GynecologyMaastricht, The Netherlands.
RP Koeneman, MM (reprint author), Maastricht University, Medical Centre, Department of Obstetrics and Gynecology, Maastricht, The Netherlands.
EM margot.koeneman@mumc.nl
CR zur Hausen H, 2000, Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92(9):690–698
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Trimble CL, Piantadosi S, Gravitt P, Ronnett B, Pizer E, Elko A et al, 2005, Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type andHLA phenotype. Clin Cancer Res 11(13):4717–4723
Ovestad IT, Gudlaugsson E, Skaland I, Malpica A, Munk AC, Janssen EA et al, 2011, The impact of epithelial biomarkers, local immune response and human papillomavirus genotype in the regression of cervical intraepithelial neoplasia grades 2-3. J Clin Pathol 64(4):303–307
Munk AC, Gudlaugsson E, Ovestad IT, Lovslett K, Fiane B, Hidle B et al, 2012, Interaction of epithelial biomarkers, local immune response and condom use in cervical intraepithelial neoplasia 2-3 regression. Gynecol Oncol 127(3):489–494
Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB et al, 2012, Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol 120(1):152–159
Barken SS, Rebolj M, Andersen ES, Lynge E, 2012, Frequency of cervical intraepithelial neoplasia treatment in a well-screened population. Int J Cancer 130(10):2438–2444
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Litjens RJ, Hopman AH, van deVijver KK, Ramaekers FC, Kruitwagen RF, Kruse AJ, 2013, Molecular biomarkers in cervical cancer diagnosis: a critical appraisal. Expert Opin Med Diagn 7(4):365–377
Koeneman MM, Kruitwagen RF, Nijman HW, Slangen BF, Van Gorp T, Kruse AJ, 2015, Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers. Expert Rev Mol Diagn 15(4):527–546
Thomas LK, Bermejo JL, Vinokurova S, Jensen K, Bierkens M, Steenbergen R et al, 2014, Chromosomal gains and losses in human papillomavirus-associated neoplasia of the lower genital tract - a systematic review and meta-analysis. Eur J Cancer 50(1):85–98
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Alameda F, Espinet B, Corzo C, Munoz R, Bellosillo B, Lloveras B et al, 2009, 3q26, hTERC, gain studied by fluorescence in situ hybridization as a persistence-progression indicator in low-grade squamous intraepithelial lesion cases. Hum Pathol 40(10):1474–1478
Jalali GR, Herzog TJ, Dziura B, Walat R, Kilpatrick MW, 2010, Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytologic finding. Am J Obstet Gynecol 202:581.e1-5
Lan YL, Yu L, Jia CW, Wu YM, Wang SY, 2012, Gain of human telomerase RNA gene is associated with progression of cervical intraepithelial neoplasia grade I or II. Chin Med J 125(9):1599–1602
Rodolakis A, Biliatis I, Symiakaki H, Kershnar E, Kilpatrick MW, HaidopoulosDet al, 2012, Role of chromosome 3q26 gain in predicting progression of cervical dysplasia. Int J Gynecol Cancer 22(5):742–747
Obermann EC, Savic Prince S, Barascud A, Grilli B, Herzog M, Kaup D et al, 2013, Prediction of outcome in patients with lowgrade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC. Cancer Cytopathol 121(8):423–431
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 549
EP 557
DI 10.1007/s12253-018-0480-y
PG 9
ER
PT J
AU Salem, MS
Hamed, RA
Fayez, GA
Eldeen, NG
AF Salem, M Sohair
Hamed, R Ahmed
Fayez, G Alaaeldin
Eldeen, Nour Ghada
TI Non-target Genes Regulate miRNAs-Mediated Migration Steering of Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MiRNAs; colorectal carcinoma; Non-target genes; MAP4K4; Migration
ID MiRNAs; colorectal carcinoma; Non-target genes; MAP4K4; Migration
AB MicroRNAs (miRNAs) trigger a two-layer regulatory network directly or through transcription factors and their co-regulators. Unlike miR-375, the role of miR-145 and miR-224 in inhibiting or driving cancer cell migration is controversial. This study is a step towards addressing the potential of miR-375, miR-145 and miR-224 expression modulation to inhibit colorectal carcinoma (CRC) cells migration in vitro through regulation of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44. Transwell migration assay results revealed a significant subdue of migration ability of cells transfected with miR-375 and miR-145 mimics and miR-224 inhibitor. Real time PCR data showed that expression of VEGFA, TGFβ1, IGF1, CD105 and CD44 was downregulated as a consequence of exogenous re-expression of miR-375 and inhibition of miR-224. On the other hand, ectopic expression of miR-145 did not affect VEGFA, TGFβ1 and CD44 expression, while it elevated CD105 and suppressed IGF1 expression. MAP4K4, a predicted target of miR-145, was validated as a target that could play a role in miR-145-mediated regulation of migration. At mRNA level, no change was observed in expression of MAP4K4 in cells with restored expression of miR-145, while western blotting analysis revealed a 25% reduction of protein level. By applying luciferase reporter assay, a significant decrease in luciferase activity was observed, supporting that miR-145 directly target 3’ UTR of MAP4K4. The study highlighted the involvement of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44 in mediating anti- and pro-migratory effect of miR-375 and miR-224, respectively, and validated MAP4K4 as a direct target of anti-migratory miR-145.
C1 [Salem, M Sohair] National Research Centre, Molecular Genetics and Enzymology Department, 33 El-Buhouth St., Dokki, 12622 Giza, Egypt.
[Hamed, R Ahmed] National Research Centre, Phytochemistry Department, 33 El-Buhouth St., Dokki, 12622 Giza, Egypt.
[Fayez, G Alaaeldin] National Research Centre, Molecular Genetics and Enzymology Department, 33 El-Buhouth St., Dokki, 12622 Giza, Egypt.
[Eldeen, Nour Ghada] National Research Centre, Molecular Genetics and Enzymology Department, 33 El-Buhouth St., Dokki, 12622 Giza, Egypt.
RP Salem, MS (reprint author), National Research Centre, Molecular Genetics and Enzymology Department, 12622 Giza, Egypt.
EM ssalem_nrc@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 559
EP 566
DI 10.1007/s12253-018-0502-9
PG 8
ER
PT J
AU Hu, H
Wang, T
Pan, R
Yang, Y
Li, B
Zhou, C
Zhao, J
Huang, Y
Duan, Sh
AF Hu, Haochang
Wang, Tiangong
Pan, Ranran
Yang, Yong
Li, Bin
Zhou, Cong
Zhao, Jun
Huang, Yi
Duan, Shiwei
TI Hypermethylated Promoters of Secreted Frizzled-Related Protein Genes are Associated with Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SFRP1; SFRP2; DNA methylation; Colorectal cancer; Quantitative methylation specific PCR
ID SFRP1; SFRP2; DNA methylation; Colorectal cancer; Quantitative methylation specific PCR
AB Colorectal cancer (CRC) is one of the leading causes of death worldwide. Aberrant DNA methylation has been recognized as one of the most common molecular alterations in CRC. The goal of this study was to investigate the diagnostic value of SFRP1 and SFRP2 methylation for CRC. A total of 80 pairs of CRC patients were recruited to test the association of SFRP1 and SFRP2 promotor methylation with CRC. Methylation assay was performed using quantitative methylation-specific polymerase chain reaction (qMSP) method. In this study, we found the methylation levels of SFRP1 and SFRP2 in CRC tumor tissues were significantly higher than those in the adjacent non-tumor tissues (SFRP1: P = 2E-5; SFRP2: P = 0.014). Further bioinformatics analysis of TCGA data confirmed the association of the two genes with CRC (SFRP1: P = 7E-21; SFRP2: P = 5E-24). Luciferase reporter gene assay showed that the recombinant plasmids with SFRP1 and SFRP2 fragments could significantly enhance promoter activity (SFRP1: P = 0.002; SFRP2: P = 0.004). In addition, SFRP1 and SFRP2 methylation were inversely correlated with the mRNA expression displayed by TCGA data mining (SFRP1: r = −0.432, P = 4E-11; SFRP2: r = −0.478, P = 1E-13). GEO data analysis indicated that SFRP1 and SFRP2 expression were increased in three CRC cell lines (COLO320, HCT116 and HT29) after 5′-AZA-deoxycytidine treatment, suggesting that DNA methylation played an important role in regulating gene expression of the two genes. Our results confirmed that promoter methylation of SFRP1 and SFRP2 contributed to the risk of CRC.
C1 [Hu, Haochang] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Wang, Tiangong] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Pan, Ranran] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Yang, Yong] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Li, Bin] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Zhou, Cong] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Zhao, Jun] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
[Huang, Yi] Ningbo University, School of Medicine, Ningbo First Hospital, Department of NeurosurgeryNingbo, Zhejiang, China.
[Duan, Shiwei] Ningbo University, School of Medicine, Medical Genetics CenterNingbo, Zhejiang, China.
RP Duan, Sh (reprint author), Ningbo University, School of Medicine, Medical Genetics Center, Ningbo, China.
EM duanshiwei@nbu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 567
EP 575
DI 10.1007/s12253-018-0505-6
PG 9
ER
PT J
AU Durak, GM
Canda, T
Yilmaz, B
Seker, SN
Kokkoz, ES
Alicikus, AZ
Akturk, N
Gorken, BI
Ellidokuz, H
Sevinc, IA
Saydam, S
Sarioglu, S
AF Durak, Guray Merih
Canda, Tulay
Yilmaz, Betul
Seker, Sena Nazli
Kokkoz, Eryigit Seda
Alicikus, Arican Zumre
Akturk, Nesrin
Gorken, Bilkay Ilknur
Ellidokuz, Hulya
Sevinc, Ibrahim Ali
Saydam, Serdar
Sarioglu, Sulen
TI Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Tumor deposits; Axillary dissection; Prognosis
ID Breast cancer; Tumor deposits; Axillary dissection; Prognosis
AB Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27–82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5–161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.
C1 [Durak, Guray Merih] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
[Canda, Tulay] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
[Yilmaz, Betul] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
[Seker, Sena Nazli] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
[Kokkoz, Eryigit Seda] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
[Alicikus, Arican Zumre] Dokuz Eylul University, Faculty of Medicine, Department of Radiation OncologyIzmir, Turkey.
[Akturk, Nesrin] Dokuz Eylul University, Faculty of Medicine, Department of Radiation OncologyIzmir, Turkey.
[Gorken, Bilkay Ilknur] Dokuz Eylul University, Faculty of Medicine, Department of Radiation OncologyIzmir, Turkey.
[Ellidokuz, Hulya] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Sevinc, Ibrahim Ali] Dokuz Eylul University, Faculty of Medicine, Department of General SurgeryIzmir, Turkey.
[Saydam, Serdar] Dokuz Eylul University, Faculty of Medicine, Department of General SurgeryIzmir, Turkey.
[Sarioglu, Sulen] Dokuz Eylul University, Faculty of Medicine, Department of Pathology, Inciralti, 35340 Izmir, Turkey.
RP Durak, GM (reprint author), Dokuz Eylul University, Faculty of Medicine, Department of Pathology, 35340 Izmir, Turkey.
EM merihguray@yahoo.com
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Ratto C, Ricci R, Rossi C, Morelli U, Vecchio FM, Doglietto GB, 2002, Mesorectal microfoci adversely affect the prognosis of patients with rectal cancer. Dis Colon Rectum 45:733–742
ShimadaY, TakiiY(2010, Clinical impact ofmesorectal extranodal cancer tissue in rectal cancer: detailed pathological assessment using whole-mount sections. Dis Colon Rectum 53:771–778
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Goldstein NS, Turner JR, 2000, Pericolonic tumour deposits in patients with T3N+M0 colon adenocarcinomas: markers of reduced disease free survival and intra-abdominal metastases and their implications for TNM classification. Cancer 88:2228–2238
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 577
EP 583
DI 10.1007/s12253-018-0515-4
PG 7
ER
PT J
AU Kotowski, U
Kadletz, L
Schneider, S
Oberndorfer, F
Erovic, MB
Grasl, ChM
Lill, C
Heiduschka, G
AF Kotowski, Ulana
Kadletz, Lorenz
Schneider, Sven
Oberndorfer, Felicitas
Erovic, M Boban
Grasl, Ch Matthaeus
Lill, Claudia
Heiduschka, Gregor
TI ELMO3 – a Negative Prognostic Marker in Minor Salivary Gland Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ELMO3; Molecular prognostic marker; Minor salivary gland cancer; Immunohistochemistry
ID ELMO3; Molecular prognostic marker; Minor salivary gland cancer; Immunohistochemistry
AB Engulfment and cell motility 3 protein (ELMO3) is a protein that is involved in cell migration and promotes the remodeling of the cytoskeleton. Moreover, it is described as a prognostic marker in several cancers. The aim of this study was to evaluate ELMO3 expression in patients with minor salivary gland carcinoma. The expression of ELMO3 was examined by immunohistochemistry. The intensity of staining was evaluated and data was correlated to clinical outcome. Forty-six patients with complete clinical data were included into statistical analysis. ELMO3 expression was observed in 85% of the cases. High staining intensity of ELMO3 correlated with a significantly worse disease free survival (p = .0495) and a higher recurrence rate (p = .0071). In conclusion, it is still difficult to predict the clinical outcome of patients with minor salivary gland carcinoma. Evaluation of ELMO3 might serve as a clinical prognostic marker in future.
C1 [Kotowski, Ulana] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Kadletz, Lorenz] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Schneider, Sven] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Oberndorfer, Felicitas] Medical University of Vienna, Department of Pathology, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Erovic, M Boban] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Grasl, Ch Matthaeus] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Lill, Claudia] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
[Heiduschka, Gregor] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
RP Lill, C (reprint author), Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, 1090 Vienna, Austria.
EM claudia.lill@meduniwien.ac.at
CR Strick MJ, Kelly C, Soames JV, McLean NR, 2004, Malignant tumours of the minor salivary glands–a 20 year review. Br J Plast Surg 57:624–631. , DOI 10.1016/j.bjps.2004.04.017
Barnes L, World Health Organization, International Agency for Research on Cancer, 2005, Pathology and genetics of head and neck Tumours. IARC
Jones AS, Beasley NJ, Houghton DJ, Helliwell TR, Husband DJ, 1998, Tumours of the minor salivary glands. Clin Otolaryngol Allied Sci 23:27–33
Lopes MA, Santos GC, Kowalski LP, 1998, Multivariate survival analysis of 128 cases of oral cavity minor salivary gland carcinomas. Head Neck 20:699–706
Vander Poorten VL, Balm AJ, Hilgers FJ et al, 2000, Stage as major long term outcome predictor in minor salivary gland carcinoma. Cancer 89:1195–1204
Erovic BM, Schopper C, Pammer J, Vormittag L, Maleki A, Brunner M, Heiduschka G, Grasl MC, Thurnher D, 2010, Multimodal treatment of patients with minor salivary gland cancer in the case of recurrent disease. Head Neck 32:1167–1172. https:// doi.org/10.1002/hed.21312
Carrillo JF,Maldonado F, Carrillo LC, Ramirez-OrtegaMC, Pizano JGG, Melo C, Chanona JG, Luna-Ortiz K, Ocana LFO, 2011, Prognostic factors in patients with minor salivary gland carcinoma of the oral cavity and oropharynx. Head Neck 33:1406–1412. , DOI 10.1002/hed.21641
Schneider S, Thurnher D, Seemann R, Brunner M, Kadletz L, GhanimB, Aumayr K, Heiduschka G, Lill C, 2016, The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival. Eur Arch Otorhinolaryngol 273:1283–1292. , DOI 10.1007/s00405- 015-3609-6
Goyette M-A, Cote J-F, 2014, NSCLC metastasis: going with ELMO3. Oncotarget 5:5850–5851. , DOI 10.18632/ oncotarget.2341
Fan W, Yang H, Xue H, Sun Y, Zhang J, 2015, ELMO3 is a novel biomarker for diagnosis and prognosis of non-small cell lung cancer. Int J Clin Exp Pathol 8:5503–5508
Kristensen LS, Soes S, Hansen LL, 2014, ELMO3: a direct driver of cancer metastasis? Cell Cycle 13:2483–2484. , DOI 10. 4161/15384101.2014.947228
Kadletz L, Heiduschka G, Wiebringhaus R, Gurnhofer E, Kotowski U, Haymerle G, Brunner M, Barry C, Kenner L, 2016, ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinoma - a short report. Cell Oncol, Dordr, 40:193–198. , DOI 10.1007/s13402-016- 0310-8
Haymerle G, Kadletz L, Wiebringhaus R, Golabi B, Mildner M, Thurnher D, Heiduschka G, 2017, ELMO3 predicts poor outcome in T1 laryngeal cancer. Clin Otolaryngol 42:1181–1186. https://doi. org/10.1111/coa.12845
Soes S, Daugaard IL, Sorensen BS, Carus A,MattheisenM, Alsner J, Overgaard J, Hager H, Hansen LL, Kristensen LS, 2014, Hypomethylation and increased expression of the putative oncogene ELMO3 are associated with lung cancer development and metastases formation. Oncoscience 1:367–374. , DOI 10. 18632/oncoscience.42
Coskun M, Boyd M, Olsen J, Troelsen JT, 2010, Control of intestinal promoter activity of the cellular migratory regulator gene ELMO3 by CDX2 and SP1. J Cell Biochem 109:1118–1128. , DOI 10.1002/jcb.22490
Kadletz L, Bigenzahn J, Thurnher D, Stanisz I, Erovic BM, Schneider S, Schmid R, Seemann R, Birner P, Heiduschka G, 2015, Evaluation of polo-like kinase 1 as a potential therapeutic target in Merkel cell carcinoma. Head Neck 38:E1918–E1925. , DOI 10.1002/hed.24349
Baddour HM Jr, Fedewa SA, Chen AY, 2016, Five- and 10-year cause-specific survival rates in carcinoma of the minor salivary gland. JAMA Otolaryngol Head Neck Surg 142:67–73. https:// doi.org/10.1001/jamaoto.2015.2805
Loh KS, Barker E, Bruch G, O'Sullivan B, Brown DH, Goldstein DP, Gilbert RW, Gullane PJ, Irish JC, 2009, Prognostic factors in malignancy of the minor salivary glands. Head Neck 31:58–63. , DOI 10.1002/hed.20924
Anderson JN, Beenken SW, Crowe R, Soong SJ, Peters G, Maddox WA, Urist MM, 1995, Prognostic factors in minor salivary gland cancer. Head Neck 17:480–486
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 585
EP 591
DI 10.1007/s12253-018-0475-8
PG 7
ER
PT J
AU Kumar, P
Surya, V
Urs, BA
Augustine, J
Mohanty, S
Gupta, S
AF Kumar, Priya
Surya, Varun
Urs, B Aadithya
Augustine, Jeyaseelan
Mohanty, Sujata
Gupta, Sunita
TI Sarcomas of the Oral and Maxillofacial Region: Analysis of 26 Cases with Emphasis on Diagnostic Challenges
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sarcoma; Oral and maxillofacial region; Molecular diagnostics
ID Sarcoma; Oral and maxillofacial region; Molecular diagnostics
AB Sarcomas of the Oral and Maxillofacial Region (SOMR) are rare lesions which pose diagnostic and management challenges.We analyzed 26 cases of SOMR with respect to clinical presentation, histopathological subtype, treatment modalities, recurrence, and treatment outcome. In our series, Osteosarcoma (OS) was the most common type of sarcoma (7 cases), followed by 5 cases of Ewing’s Sarcoma (ES), 3 cases each of Chondrosarcoma (CS) and Leiomyosarcoma (LMS), 2 cases each of Malignant Peripheral Nerve Sheath Tumor (MPNST), Pleomorphic Undifferentiated Sarcoma (PUS), Myeloid Sarcoma (MS)and Rhabdomyosarcoma (RMS). Surgery was the primary treatment modality in most cases and was combined with adjuvant chemo/ radiotherapy in few cases. 24 of the 26 cases were followed up for an average period of 40.67 months. Adverse disease outcomes like recurrence were seen in 2 cases whereas death due to the disease was reported in 7 cases. In view of the diagnostic challenges faced in SOMRs, it appears practical to stress on the underlying genetic aspects of the disease process rather than histological subtyping to improve disease outcome.
C1 [Kumar, Priya] Maulana Azad Institute of Dental Sciences, Department of Oral Pathology, 7th floorNew Delhi, India.
[Surya, Varun] Maulana Azad Institute of Dental Sciences, Department of Oral Pathology, 7th floorNew Delhi, India.
[Urs, B Aadithya] Maulana Azad Institute of Dental Sciences, Department of Oral Pathology, 7th floorNew Delhi, India.
[Augustine, Jeyaseelan] Maulana Azad Institute of Dental Sciences, Department of Oral Pathology, 7th floorNew Delhi, India.
[Mohanty, Sujata] Maulana Azad Institute of Dental Sciences, Department of Oral and Maxillofacial SurgeryNew Delhi, India.
[Gupta, Sunita] Maulana Azad Institute of Dental Sciences, Department of Oral Medicine & RadiologyNew Delhi, India.
RP Kumar, P (reprint author), Maulana Azad Institute of Dental Sciences, Department of Oral Pathology, New Delhi, India.
EM drpri_kumar@yahoo.com
CR KrausDHSarcomas of the head and neck. Curr Oncol Rep 4:68–75
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 593
EP 601
DI 10.1007/s12253-018-0510-9
PG 9
ER
PT J
AU Okuyama, K
Fukushima, H
Naruse, T
Yanamoto, S
Tsuchihashi, H
Umeda, M
AF Okuyama, Kohei
Fukushima, Hiromasa
Naruse, Tomofumi
Yanamoto, Souichi
Tsuchihashi, Hiroki
Umeda, Masahiro
TI CD44 Variant 6 Expression and Tumor Budding in the Medullary Invasion Front of Mandibular Gingival Squamous Cell Carcinoma Are Predictive Factors for Cervical Lymph Node Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD44 variant 6; Tumor budding; Mandibular gingival squamous cell carcinoma; Medullary invasion; Cervical lymph node metastasis
ID CD44 variant 6; Tumor budding; Mandibular gingival squamous cell carcinoma; Medullary invasion; Cervical lymph node metastasis
AB Oral squamous cell carcinoma (OSCC) with invasion into the mandibular medullary space has been reported to be a predictive factor for cervical lymph node metastasis (CLNM). As CLNM has been associated with the stemness of cancer cells, we aimed to evaluate the relationship between clinical characteristics and immunohistochemical findings on the invasion front of the medullary invasive OSCC and CLNM. The medical records of 25 patients with the mandibular medullary invasive OSCC who were performed mandibulectomy and neck dissection in our department from 2010 to 2016 were examined. Serial sections were stained with antibodies against CD44 variant 6 (CD44v6) to examine cancer stemness and to evaluate the number of tumor buds in the medullary invasion front of the mandibular invasive OSCC. Categorical data were analyzed by Fisher’s exact test. The expression of CD44v6 and the number of tumor buds between the groups with and without pathological CLNM (CLNM+ and CLNM-, respectively) were analyzed using the Mann-Whitney U test. Of the 25 patients, 11 patients were CLNM+. Of the several measured variables, histologic differentiation of the mandibular invasive OSCC was a significant factor for CLNM+. CD44v6 expression and tumor bud formation in the medullary invasion front of the mandibular invasive OSCC were significantly higher in the CLNM+ group, suggests that both CD44v6 and tumor budding in the medullary invasion front are predictive factors for CLNM.
C1 [Okuyama, Kohei] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1, Sakamoto, Nagasaki-shi, 852-8588 Nagasaki, Japan.
[Fukushima, Hiromasa] Nagasaki University, School of DentistryNagasaki, Japan.
[Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1, Sakamoto, Nagasaki-shi, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1, Sakamoto, Nagasaki-shi, 852-8588 Nagasaki, Japan.
[Tsuchihashi, Hiroki] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1, Sakamoto, Nagasaki-shi, 852-8588 Nagasaki, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1, Sakamoto, Nagasaki-shi, 852-8588 Nagasaki, Japan.
RP Okuyama, K (reprint author), Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 852-8588 Nagasaki, Japan.
EM okuyamak@nagasaki-u.ac.jp
CR Rautava J, Luukkaa M, Heikinheimo K, Alin J, Grenman R, Happonen RP, 2007, Squamous cell carcinomas arising from different types of oral epithelia differ in their tumor and patient characteristics and survival. Oral Oncol 43:911–919
Shingaki S, Nomura T, Takada M, Kobayashi T, Suzuki I, Nakajima T, 2002, Squamous cell carcinomas of the mandibular alveolus: analysis of prognostic factors. Oncology 62:17–24
Fitzpatrick SG, Neuman AN, Cohen DM, Bhattacharyya I, 2012, The clinical and histologic presentation of gingival squamous cell carcinoma: a study of 519 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 114:509–515
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Okura M, Yanamoto S, Umeda M, Otsuru M, Ota Y, Kurita H, Kamata T, Kirita T, Yamakawa N, Yamashita T, Ueda M, Komori T, Hasegawa T, Aikawa T, Japan Oral Oncology Group, 2016, Prognostic and staging implications of mandibular canal invasion in lower gingival squamous cell carcinoma. Cancer Med 5:3378– 3385
Matsushita Y, Yanamoto S, Yamada S, Mori H, Adachi M, Takahashi H, Naruse T, Ikeda H, Shiraishi T, Minamikawa T, Shibuya Y, Komori T, Asahina I, Umeda M, 2015, Correlation between degree of mandibular bone invasion and prognosis in carcinoma of the mandibular gingiva: soft tissue classification based on UICC classification. J Oral Maxillofac Surg Med Pathol 27: 631–636
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Nomura T, Shibahara T, Cui NH, Noma H, 2005, Patterns of mandibular invasion by gingival squamous cell carcinoma. J Oral Maxillofac Surg 63:1489–1493
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 603
EP 609
DI 10.1007/s12253-018-0529-y
PG 7
ER
PT J
AU Alabiad, AM
Harb, AO
Taha, FH
Shafaay, ShEB
Gertallah, ML
Salama, N
AF Alabiad, Ali Mohamed
Harb, A Ola
Taha, F Heba
Shafaay, Sh El Basant
Gertallah, M Loay
Salama, Nashaat
TI Prognostic and Clinic-Pathological Significances of SCF and COX-2 Expression in Inflammatory and Malignant Prostatic Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SCF; COX-2; Prostatic adenocarcinoma; Immunohistochemistry; Prognosis
ID SCF; COX-2; Prostatic adenocarcinoma; Immunohistochemistry; Prognosis
AB The initiation of prostatic malignancy has been linked to chronic inflammation. Stem cell factor (SCF) is an inflammatory cytokine that is specific to the c-KIT receptor which is type III receptor tyrosine kinase (RTK). Cyclooxygenases (COXs) are themain enzymes which are responsible for prostaglandins production from arachidonic acid. COX2 is an enzyme which is produced under different pathological conditions. The aim of our study; is to investigate the clinicopathological and the prognostic significance of SCF and COX-2 expression in prostatic adenocarcinoma (PC), chronic prostatitis and nodular prostatic hyperplasia (NPH) in a trial to clarify the role of inflammation as a risk factor for prostatic carcinogenesis and cancer progression. SCF and COX-2 tissue protein expression were evaluated in 50 cases of PC, 20 cases of chronic prostatitis and 10 cases of NPH using immunohistochemistry, patients were followed up for 5 years. The relationship between their levels of expressions, clinicopathological, and prognostic criteria were studied. SCF expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.010), higher Gleason score (p = 0.011). COX-2 expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.016), advanced D’Amico risk group (p = 0.038). High levels of expression of both SCF& COX-2 are associated with higher incidence of tumor relapse, worse disease overall survival and free survival (p < 0.001). SCF and COX-2 are associated with PC progression and associated with poor prognosis in PC patients.
C1 [Alabiad, Ali Mohamed] Zagazig University, Faculty of Medicine, Pathology DepartmentZagazig, Egypt.
[Harb, A Ola] Zagazig University, Faculty of Medicine, Pathology DepartmentZagazig, Egypt.
[Taha, F Heba] Zagazig University, Faculty of Medicine, Medical Oncology DepartmentZagazig, Egypt.
[Shafaay, Sh El Basant] Zagazig University, Faculty of Medicine, Clinical Oncology and Nuclear Medicine DepartmentZagazig, Egypt.
[Gertallah, M Loay] Zagazig University, Faculty of Medicine, General Surgery DepartmentZagazig, Egypt.
[Salama, Nashaat] Zagazig University, Faculty of Medicine, Urology DepartmentZagazig, Egypt.
RP Harb, AO (reprint author), Zagazig University, Faculty of Medicine, Pathology Department, Zagazig, Egypt.
EM olaharb2015@gmail.com
CR Xu F, Li M, Zhang C, Cui J, Liu J, Li J, Jiang H, 2017, Clinicopathological and prognostic significance of COX-2 Immunohistochemical expression in breast Cancer: a meta-analysis. Oncotarget 8(4):6003–6012. , DOI 10.18632/ oncotarget.13990
Yoo S, Se YC, You D, Kim CS, 2016, New drugs in prostate Cancer. Prostate International 4(2):37–42. , DOI 10.1016/ j.prnil.2016.05.001
Abeshouse A, Ahn J, Akbani R, Ally A, Amin S, Andry CD, Annala M et al, 2016, Prostate Cancer. N Engl J Med 58(1):1–6. , DOI 10.1017/CBO9781107415324.004.
Lee KC, Cho IR, 2017, Chronic prostatitis/chronic pelvic pain syndrome in adolescents compared with that in young adults. Investigative and clinical urology 58(4):267–270
Cardoso HJ, Figueira MI, Socorro S, 2017, The stem cell factor, SCF)/c-KIT signaling in testis and prostate cancer. Journal of cell communication and signaling 11(4):297–307
Tayel SI, El-Hefnway SM, El Gayed EMA, Abdelaal GA, 2017, Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma. Respir Res 18(1):21
Huang, Bo, Zhang Lei, Gui-mei Zhang, Dong Li, Chuanwang Song, Bo Li, Yanyan Liu, et al. 2014. BSCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment^. 112, 4): 1269–1279. , DOI 10.1182/blood-2008-03-147033
Bilani N, Bahmad H, Abou-Kheir W, 2017, Prostate cancer and aspirin use: synopsis of the proposed molecular mechanisms. Front Pharmacol 8:145
Calisma, Immunohistokimyasal, 2016, BImmunohistochemical Study of Cyclooxygenase-2 Expression in Prostate Carcinoma : It ’ S Relation with Apoptosis and Angiogenesis^. 144–147
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Wang X, Dong J, Jia L, Zhao T, LangM, Li Z, Qin T, 2017, HIF-2- dependent expression of stem cell factor promotes metastasis in hepatocellular carcinoma. Cancer Lett 393:113–124
Bellone G, Smirne C, Carbone A, Buffolino A, Scirelli T, Prati A, Emanuelli G, 2006, KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes. Int J Oncol 29(4):851–859
Gao C, Li S, Zhao T, Chen J, Ren H, Zhang H, Zhao X, 2015, SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression. PLoS One 10(3):e0121338
Yasuda A, Sawai H, Takahashi H, Ochi N, Matsuo Y, Funahashi H, Sato M, Okada Y, Takeyama H, Manabe T, 2006, The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic Cancer cells. Mol Cancer 5:46. , DOI 10.1186/ 1476-4598-5-46.
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Eberle F, Leinberger FH, Saulich MF, Seeger W, Engenhart- Cabillic R, Hanze J, Hattar K, Dikomey E, Subtil FSB, 2017, In Cancer cell lines inhibition of SCF/c-kit pathway leads to Radiosensitization only when SCF is strongly over-expressed. Clinical and Translational Radiation Oncology 2:69–75. https:// doi.org/10.1016/j.ctro.2017.02.001
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Wang W, Bergh A, Damber JE, 2005, Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor neovascularization in human prostate cancer. Clin Cancer Res 11(9):3250– 3256
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Malaysiana S, Siklooksigenase PT, Prostat A, Gred M, National Cancer Registry, 2015, High expression of Cyclooxygenase-2 in high grade human prostate adenocarcinoma. In: 44, 5): 727–33
Khor LY, BaeK, Pollack A, Elizabeth H Hammond M, Grignon DJ, Venkatesan VM, Rosenthal SA et al, 2007, COX-2 expression predicts prostate-Cancer outcome: analysis of data from the RTOG 92-02 trial. Lancet Oncol 8(10):912–920. , DOI 10.1016/S1470-2045(07)70280-2
Richardsen E, Uglehus RD, Due J, Busch C, Busund LT, 2010, COX-2 is overexpressed in primary prostate cancer with metastatic potential and may predict survival. A comparison study between COX-2, TGF-β, IL-10 and, Ki67. Cancer Epidemiol 34(3):316– 322
Xu F, Li M, Zhang C, Cui J, Liu J, Li J, Jiang H, 2017, Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis. Oncotarget 8(4):6003–6012
Mukherjee R, Edwards J, Underwood MA, Bartlett JM, 2005, The relationship between angiogenesis and cyclooxygenase-2 expression in prostate cancer. BJU Int 96(1):62–66
Ceylan Y, Lekili M, Muezzinoglu T, Nese N, Isisag A, 2016, Predictive value of cyclooxygenase-2 over-expression for identifying prostate cancer from benign prostatic hyperplasia in prostate biopsy specimens. Minerva urologica e nefrologica= The Italian journal of urology and nephrology 68(3):255–262
Khodier MM, Mohmoud SA, Gabal SM, Abou-Sriea MA, 2009, Cyclooxygenase-2, COX-2, expression in Egyptian cases of benign prostatic hyperplasia and prostatic adenocarcinoma. Acad J Cancer Res 2(1):33–39
Kim BH, Kim CI, Chang HS, Choe MS, Jung HR, Kim DY, Park CH, 2011, Cyclooxygenase-2 overexpression in chronic inflammation associated with benign prostatic hyperplasia: is it related to apoptosis and angiogenesis of prostate cancer? Korean journal of urology 52(4):253–259
Madaan S, Abel PD, Chaudhary KS, Hewitt R, Stott MA, Stamp GWH, Lalani EN, 2000, Cytoplasmic induction and overexpression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment. BJU Int 86(6):736–741
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 611
EP 624
DI 10.1007/s12253-018-0534-1
PG 14
ER
PT J
AU Kiraly, G
Hargitai, Z
Kovacs, I
Szeman-Nagy, G
Juhasz, I
Banfalvi, G
AF Kiraly, Gabor
Hargitai, Zoltan
Kovacs, Ilona
Szeman-Nagy, Gabor
Juhasz, Istvan
Banfalvi, Gaspar
TI Metastatic Spread from Abdominal Tumor Cells to Parathymic Lymph Nodes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoma cell line; Murine metastasis model; Parathymic lymph node; Colloidal ink
ID Carcinoma cell line; Murine metastasis model; Parathymic lymph node; Colloidal ink
AB Metastatic studies on rats showed that after subrenal implantation of tumor cells under the capsule of the kidney or subhepatic implantation under Glisson’s capsule of the liver generated primary tumors in these organs. It was assumed that tumor cells that escaped through the disrupted peripheral blood vessels of primary tumors entered the peritoneal cavity, crossed the diaphragm, and appeared in the thoracal, primarily in the parathymic lymph nodes. This explanation did not answer the question whether distant lymph nodes were reached via the blood stream from the primary tumor or through the thoracal lymphatic vessels. In this work, we investigated the metastatic pathway in C3H/HeJ mice, after direct intraperitoneal administration of murine SCC VII cells bypassing the hematogenic spread of tumor cells. The direct pathway was also mimicked by intraperitoneal injection of Pelican Ink colloidal particles, which appeared in the parathymic lymph nodes, similarly to the tumor cells that caused metastasis in the parathymic lymph nodes and in the thymic tissue. The murine peritoneal-parathymic lymph node route indicates a general mechanism of tumor progression from the abdominal effusion. This pathway starts with the growth of abdominal tumors, continues as thoracal metastasis in parathymic lymph nodes and may proceed as mammary lymph node metastasis.
C1 [Kiraly, Gabor] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, 1 Egyetem Square, 4010 Debrecen, Hungary.
[Hargitai, Zoltan] Kenezy Teaching Hospital, Department of Pathology, 2-28 Bartok Street, 4031 Debrecen, Hungary.
[Kovacs, Ilona] Kenezy Teaching Hospital, Department of Pathology, 2-28 Bartok Street, 4031 Debrecen, Hungary.
[Szeman-Nagy, Gabor] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, 1 Egyetem Square, 4010 Debrecen, Hungary.
[Juhasz, Istvan] University of Debrecen, Department of Surgery and Operative Techniques, 98 Nagyerdei korut, 4012 Debrecen, Hungary.
[Banfalvi, Gaspar] University of Debrecen, Faculty of Medicine, Department of Medical Microbiology, 1 Egyetem Square, 4010 Debrecen, Hungary.
RP Juhasz, I (reprint author), University of Debrecen, Department of Surgery and Operative Techniques, 4012 Debrecen, Hungary.
EM ji@med.unideb.hu
CR Trencsenyi G, Kertai P, Somogyi C, Nagy G, Dombradi Z, Gacsi M, Banfalvi G, 2007, Chemically induced carcinogenesis affecting chromatin structure in rat hepatocarcinoma cells. DNA Cell Biol 26:649–655 http://online.liebertpub.com/doi/abs/10.1089/dna. 2007.0587
Trencsenyi G, Kertai P, Bako F, Hunyadi J, Marian T, Hargitai Z, Pocsi I, Muranyi E, Hornyak L, Banfalvi G, 2009, Renal capsule- Parathymic lymph node complex: a new in vivo metastatic model in rats. Anticancer Res 29:2121–2126 http://ar.iiarjournals.org/ content/29/6/2121.long
Cui ZY, Ahn JS, Lee JY, Kim WS, Lim HY, Jeon HJ, Suh SW, Kim JH, Kong WH, Kang JM, Nam DH, Park K, 2006, Mouse orthotopic lung cancer model induced by PC14PE6. Cancer Res Treat 38:234–239 https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2741646/
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Jian J, Liu C, Gong Y, Su L, Zhang B, Wang Z, Wang D, Zhou Y, Xu F, Li P, Zheng Y, Song L, Zhou X, 2014, India ink incorporated multifunctional phase-transition Nanodroplets for photoacoustic/ ultrasound dual-modality imaging and photoacoustic effect based tumor therapy. Theranostics 4(10):1026–1038 http://www.thno.org/ v04p1026.htm
Rafferty P, Egenolf D, Brosnan K, Makropoulos D, Jordan J, Meshaw K, Walker M, Volk A, Bugelski PJ, 2012, Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice. J Immunotoxicol 9:43–55 http://www.tandfonline. com/doi/full/10.3109/1547691X.2011.614646
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 625
EP 633
DI 10.1007/s12253-018-0492-7
PG 9
ER
PT J
AU Ou, X
Zhang, Gt
Xu, Z
Chen, Js
Xie, Y
Liu, JK
Liu, XP
AF Ou, Xi
Zhang, Guang-tao
Xu, Zhe
Chen, Jing-sen
Xie, Yong
Liu, Ji-Kui
Liu, Xiao-Ping
TI Desumoylating Isopeptidase 2 (DESI2) Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer Cells through Regulating PI3K/AKT/mTOR Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Desumoylating isopeptidase 2; Pancreatic cancer; Phosphatidylinositide 3-kinases; AKT; mTOR
ID Desumoylating isopeptidase 2; Pancreatic cancer; Phosphatidylinositide 3-kinases; AKT; mTOR
AB This study aimed to investigate the effects of desumoylating isopeptidase 2 (DESI2) on tumor cell proliferation, apoptosis and invasion of pancreatic cancer, and to assess the signaling pathway involved. Overexpression and silence of DESI2 were designed and the experiments were divided into 5 groups: a normal control group, an interference control group (shRNA-NC); an interference group (sh-DESI2); an overexpression control group (NC), an overexpression group (DESI2). Quantitative real time polymerase chain reaction (qRT-PCR) was used to screen the appropriate interference sequence. The silencing and overexpression of DESI2 were confirmed by qRT-PCR and western blotting. Cell cycling, apoptosis, invasion, and the expression of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway and caspase 3 were measured. Overexpression and silence of DESI2 were successfully designed in two pancreatic cancer cells, and the interference effect of sh-DESI2–3 showed the best silencing effects. The biological activities of DESI2 were detected in both ASPC-1 and PANCE-1 cells. Our results showed that cell proliferation was significantly increased in the sh-DESI2 group, while decreased in DESI2 group compared with the control group in both cell lines. In ASPC-1 cells, the events in G1 phase decreased and in S phase increased obviously in the sh-DESI2 group, compared with control group. An opposite result was found when DESI2 was overexpressed. In PANCE-1 cells, the events in G2 phase were higher in the sh-DESI2 group, while in the DESI2 group was significantly lower than that in control group. In ASPC-1 and PANCE-1 cells, sh-DESI2 group showed decreased apoptosis, increased cell invasion and increased expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and decreased caspase 3 expression compared with the control group, while overexpression of DESI2 leaded to increased apoptosis, decreased cell invasion and reduced expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and increased expression of caspase 3. DESI2 regulates the proliferation and apoptosis of pancreatic cancer cells through PI3K/AKT/mTOR signaling pathway.
C1 [Ou, Xi] Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, Lian Hua Road 1120, 518036 Shenzhen, China.
[Zhang, Guang-tao] Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, Lian Hua Road 1120, 518036 Shenzhen, China.
[Xu, Zhe] The Third People’s Hospital of Shenzhen, The Third Ward of Liver Disease, 518112 Shenzhen, China.
[Chen, Jing-sen] Shenzhen Maternity and Child Healthcare Hospital, Breast Department, 518028 Shenzhen, China.
[Xie, Yong] Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, Lian Hua Road 1120, 518036 Shenzhen, China.
[Liu, Ji-Kui] Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, Lian Hua Road 1120, 518036 Shenzhen, China.
[Liu, Xiao-Ping] Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, Lian Hua Road 1120, 518036 Shenzhen, China.
RP Liu, JK (reprint author), Peking University Shenzhen Hospital, Department of Hepatopancreatobiliary Surgery, 518036 Shenzhen, China.
EM liu89201@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 635
EP 646
DI 10.1007/s12253-018-0487-4
PG 12
ER
PT J
AU Takacs, F
Tolnai-Kriston, Cs
Hernadfoi, M
Szabo, O
Szaloki, G
Szepesi,
Czeti,
Matolcsy, A
Barna, G
AF Takacs, Ferenc
Tolnai-Kriston, Csilla
Hernadfoi, Mark
Szabo, Orsolya
Szaloki, Gabor
Szepesi, Agota
Czeti, Agnes
Matolcsy, Andras
Barna, Gabor
TI The Effect of CD86 Expression on the Proliferation and the Survival of CLL Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CLL; CD86; Micro-environment; Proliferation marker
ID CLL; CD86; Micro-environment; Proliferation marker
AB Micro-environment plays important role in the pathogenesis of CLL by providing protective niche for CLL cells. Several molecules play important role in communication between CLL cells and immune cells like CD86.Some of the data suggest that CLL patients with high CD86 level need earlier treatments and cells with higher CD86 expression has higher proliferation rate but the role of CD86 in the survival and proliferation of CLL cells is unclear. We investigated the effect of CD86 expression to CLL cells in 50 peripheral blood and 15 lymph node biopsy samples from CLL patients. Our results showed that the expressions of CD86 increased significantly after 7 day culturing in medium, or in the presence of bone marrow stromal cells (BMSCs).We found positive correlation between CD86 and CD23 expression (p < 0.05), but no correlation with other markers. Furthermore, no correlation were found between the CD86 expression and the proliferation of CLL cells. Analysis of clinical data showed that cases with high CD86 expression had lower level of serum lymphocyte count (p < 0.04) at the time of the diagnosis. CD86 shows multiple appearances in the lymph nodes containing pseudofollicules, but no correlation was found between CD86 positivity, and Ki67 positivity. Our results suggest that the use of CD86 molecule as a proliferation marker for CLL is highly questionable. However, the CD86 molecule may interfere with the immune system of patients with CLL by activating and depleting immune functions. That can be the reason why CD86 positivity may mean worse prognosis.
C1 [Takacs, Ferenc] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Tolnai-Kriston, Csilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Hernadfoi, Mark] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Szabo, Orsolya] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Szaloki, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Szepesi, Agota] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Czeti, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Barna, G (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM barna.gabor@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 647
EP 652
DI 10.1007/s12253-018-0512-7
PG 6
ER
PT J
AU Li, Z
Zhang, F
Li, Y
Qi, X
Guo, Y
AF Li, Zhang
Zhang, Fengxiang
Li, Yanxin
Qi, Xiangjun
Guo, Yaming
TI Triiodothyronine Promotes Cell Proliferation of Breast Cancer via Modulating miR-204/Amphiregulin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; T3; Cell viability; miR-204; AREG
ID Breast cancer; T3; Cell viability; miR-204; AREG
AB Breast cancer (BC) severely threatens women’s life, and Triiodothyronine (T3) shows a positive role on BC cell proliferation, while the potential mechanism underlying it is still unclear. T3 was used to stimulate BC cell lines MCF-7 and T47-D. Real-time PCR was performed to determine the expression of miRNAs, while western blot was used to measure protein expression of Amphiregulin (AREG), AKT and p-AKT. The interaction between miR-204 and AREG was determined using luciferase reporter assay. MTT was performed to detect cell viability. The expression of miR-204 was decreased, while AREG and p-AKT was increased in T3 stimulated BC cell lines. T3 stimulation promoted cell viability. miR-204 targets AREG to regulate its expression. T3 promoted expression of AREG and p-AKT, while miR-204 overexpression reversed the effect of T3, however, pcDNA AREG transfection abolished the effect of miR-204 mimic. T3 promoted cell viability of BC cells via modulating the AKT signaling pathway. The detailed mechanism was that the down-regulated miR-204 that induced by T3 stimulation promoted the expression of AREG, the up-regulated AREG activated AKT signaling pathway, while the activated AKT signaling promoted cell proliferation.
C1 [Li, Zhang] Tongliao City Hospital, Department of Breast and Thyroid Surgery, No.668 Keerqin Rd., Keerqin District, 028000 Tongliao, Inner Mongolia, China.
[Zhang, Fengxiang] Tongliao City Hospital, Department of Breast and Thyroid Surgery, No.668 Keerqin Rd., Keerqin District, 028000 Tongliao, Inner Mongolia, China.
[Li, Yanxin] Tongliao City Hospital, Department of Breast and Thyroid Surgery, No.668 Keerqin Rd., Keerqin District, 028000 Tongliao, Inner Mongolia, China.
[Qi, Xiangjun] Tongliao City Hospital, Department of Breast and Thyroid Surgery, No.668 Keerqin Rd., Keerqin District, 028000 Tongliao, Inner Mongolia, China.
[Guo, Yaming] Tongliao City Hospital, Department of Breast and Thyroid Surgery, No.668 Keerqin Rd., Keerqin District, 028000 Tongliao, Inner Mongolia, China.
RP Li, Z (reprint author), Tongliao City Hospital, Department of Breast and Thyroid Surgery, 028000 Tongliao, China.
EM wupi5885@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 653
EP 658
DI 10.1007/s12253-018-0525-2
PG 6
ER
PT J
AU Cornel, MCK
Wouters, K
Van de Vijver, KK
van der Wurff, AMA
van Engeland, M
Kruitwagen, FPMR
Pijnenborg, MAJ
AF Cornel, M C Karlijn
Wouters, Kim
Van de Vijver, K Koen
van der Wurff, A M Anneke
van Engeland, Manon
Kruitwagen, F P M Roy
Pijnenborg, M A Johanna
TI Gene Promoter Methylation in Endometrial Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Methylation; Endometrial hyperplasia; Endometrial cancer; P16; K-Ras; hMLH1
ID Methylation; Endometrial hyperplasia; Endometrial cancer; P16; K-Ras; hMLH1
AB Up to 60% of untreated atypical hyperplastic endometrium will develop into endometrial carcinoma (EC), and for those who underwent a hysterectomy a coexisting EC is found in up to 50%. Gene promoter methylation might be related to the EC development. The aim of this study is to determine changes in gene promoter profiles in normal endometrium, atypical hyperplasia (AH) and EC in relation to K-Ras mutations. A retrospective study was conducted in patients diagnosed with endometrial hyperplasia with and without subsequent EC. Promoter methylation of APC, hMLh1, O6-MGMT, P14, P16, RASSF1, RUNX3 was analysed on pre-operative biopsies, and correlated to the final histological diagnosis, and related to the presence of K-Ras mutations. In the study cohort (n=98), differences in promoter methylation were observed for hMLH1, O6-MGMT, and P16. Promoter methylation of hMLH1 and O6-MGMT gradually increased from histologically normal endometrium to AH to EC; 27.3, 36.4% and 38.0% for hMLH1 and 8.3%, 18.2% and 31.4% for O6-MGMT, respectively. P16 promoter methylation was significantly different in AH (7.7%) compared to EC (38%). K-Ras mutations were observed in 12.1% of AH, and in 19.6% of EC cases. No association of K-Ras mutation with promoter methylation of any of the tested genes was found. In conclusion, hMLH1 and O6-MGMT promoter methylation are frequently present in AH, and thus considered to be early events in the carcinogenesis of EC, whereas P16 promoter methylation was mainly present in EC, and not in precursor lesions supporting a late event in the carcinogenesis.
C1 [Cornel, M C Karlijn] Maastricht University, GROW - School for Oncology and Developmental BiologyMaastricht, The Netherlands.
[Wouters, Kim] Maastricht University Medical Center, Department of PathologyMaastricht, The Netherlands.
[Van de Vijver, K Koen] Ghent University Hospital, Department of PathologyGhent, Belgium.
[van der Wurff, A M Anneke] Department of Pathology, Elisabeth-TweeStedenTilburg, The Netherlands.
[van Engeland, Manon] Maastricht University, GROW - School for Oncology and Developmental BiologyMaastricht, The Netherlands.
[Kruitwagen, F P M Roy] Maastricht University, GROW - School for Oncology and Developmental BiologyMaastricht, The Netherlands.
[Pijnenborg, M A Johanna] Radboud University Nijmegen, Medical Centre, Department of Obstetrics and GynaecologyNijmegen, The Netherlands.
RP Cornel, MCK (reprint author), Maastricht University, GROW - School for Oncology and Developmental Biology, Maastricht, The Netherlands.
EM karlijncornel@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 659
EP 667
DI 10.1007/s12253-018-0489-2
PG 9
ER
PT J
AU Lorincz, T
Holczer, M
Kapuy, O
Szarka, A
AF Lorincz, Tamas
Holczer, Marianna
Kapuy, Orsolya
Szarka, Andras
TI The Interrelationship of Pharmacologic Ascorbate Induced Cell Death and Ferroptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pharmacologic ascorbate; Cell death; ROS; Lipid peroxidation; Ferroptosis
ID Pharmacologic ascorbate; Cell death; ROS; Lipid peroxidation; Ferroptosis
AB Pharmacologic ascorbate induced cell death and ferroptosis share common features such as iron dependency, production of ROS, lipid peroxidation, caspase independency and the possible involvement of autophagy. These observations lead us to hypothesize that ferroptosis may also be involved in cancer cell death due to pharmacologic ascorbate treatment. Thus cell death of HT-1080 cell line was induced by ferroptosis inducers and pharmacologic ascorbate then the mechanism of cell death was compared. The EC50 value of pharmacologic ascorbate on HT-1080 cell line was found to be 0.5 mM that is in the range of the most ascorbate sensitive cell lines. However either of the specific inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) could not elevate the viability of pharmacologic ascorbate treated cells suggesting that ferroptosis was not involved in the pharmacologic ascorbate induced cell death. α-tocopherol that could effectively elevate the viability of erastin and RSL3 treated HT1080 cells failed to mitigate the cytotoxic effect of pharmacologic ascorbate further strengthened this assumption. Furthermore at lower concentrations (0.1–0.5 mM) ascorbate could avoid the effects of ferroptosis inducers. Our results indicate that pharmacologic ascorbate induced cytotoxicity and ferroptosis – albeit phenotypically they show similar traits – are governed by different mechanisms.
C1 [Lorincz, Tamas] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
[Holczer, Marianna] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1444 Budapest, Hungary.
[Kapuy, Orsolya] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1444 Budapest, Hungary.
[Szarka, Andras] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Szent Gellert ter 4, 1111 Budapest, Hungary.
RP Szarka, A (reprint author), Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, 1111 Budapest, Hungary.
EM szarka@mail.bme.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 669
EP 679
DI 10.1007/s12253-018-0539-9
PG 11
ER
PT J
AU Pang, Y
Liu, Z
Liu, Sh
AF Pang, Yanan
Liu, Zhiyong
Liu, Shanrong
TI Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Arsenic trioxide; Genes/proteins interaction; Bioinformatics analysis; Pancreatic cancer
ID Arsenic trioxide; Genes/proteins interaction; Bioinformatics analysis; Pancreatic cancer
AB Arsenic trioxide is an approved chemotheraputic agent for the treatment of acute promyelocytic leukemia (APL). Recently, numerous studies suggested that arsenic trioxide acts as anti-cancer roles in various human malignancies. However, the molecular mechanisms are not fully elucidated. In this study, we explored the critical targets of arsenic trioxide and their interaction network systematically by searching the publicly available published database like DrugBank (DB) and STRING. Seven direct protein targets (DPTs) and 111 DPT-associated genes were identified. The enrichment analysis of arsenic trioxide associated genes/ proteins revealed 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these pathways, phosphatidylinositol- 4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) single pathway and pancreatic cancer pathway are highly correlated with arsenic trioxide and have 5 overlapped targets. Then we investigated the gene alternation of selected critical genes in pancreatic cancer studies using cBio portal. These results indicated that arsenic trioxide could act anti-tumor function through PI3K-Akt single pathway and identified critical genes might be therapeutic targets for pancreatic cancer.
C1 [Pang, Yanan] Second Military Medical University, Changhai Hospital, Department of Laboratory Diagnostics, 200433 Shanghai, China.
[Liu, Zhiyong] Second Military Medical University, Changhai Hospital, Department of Laboratory Diagnostics, 200433 Shanghai, China.
[Liu, Shanrong] Second Military Medical University, Changhai Hospital, Department of Laboratory Diagnostics, 200433 Shanghai, China.
RP Liu, Sh (reprint author), Second Military Medical University, Changhai Hospital, Department of Laboratory Diagnostics, 200433 Shanghai, China.
EM liushanrong@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 681
EP 690
DI 10.1007/s12253-018-0543-0
PG 10
ER
PT J
AU Li, N
Tian, YW
Xu, Y
Meng, DD
Gao, L
Shen, Wj
Liu, Zl
Xu, ZQ
AF Li, Ning
Tian, Yong-Wei
Xu, Yue
Meng, Dan-Dan
Gao, Ling
Shen, Wen-jie
Liu, Zong-lan
Xu, Zhi-Qiao
TI Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autologous CIK cell; Advanced cervical cancer; Radiochemotherapy
ID Autologous CIK cell; Advanced cervical cancer; Radiochemotherapy
AB To investigate the clinical efficacy of autologous cytokine induced killer (CIK) cells transfusion combined with radiochemotherapy in the treatment of advanced cervical cancer. A total of 89 hospitalized patients with advanced cervical cancer were admitted and divided into the treatment group (44 cases, autologous CIK cells transfusion combined with radiochemotherapy) and the control group (45 cases, radiochemotherapy) by a randomized non-blind method. Comparisons of therapeutic efficacies, immune functions, life qualities and survival rates were analyzed between the two groups. The short-term therapeutic efficacy of the treatment group was significantly higher than that of the control group. There was no significant difference in 1, 2 and 3 year survival rates between the two groups. Compared with pre-treatment, levels of CD3+, CD4+/CD8+ in peripheral blood were increased in the CIK group,whichwere reduced in the control group. In the CIK group,only the feeling was depressed on the 25th day post-treatment (T25) compared with the day before treatment (B1). However in the control group, the function of body, role, social and holistic health was obvious disordered on day T25 compared with day B1. On day T25, there were significant differences in function of body, social and holistic health between two groups. Autologous CIK cells transfusion combined with radiochemotherapy shows better short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, which obviously improves immune function and life quality of patients with low side effects.
C1 [Li, Ning] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Tian, Yong-Wei] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Xu, Yue] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Meng, Dan-Dan] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Gao, Ling] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Shen, Wen-jie] Kaifeng Central Hospital, The Department of Statistics, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Liu, Zong-lan] Kaifeng Central Hospital, The Department of Statistics, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
[Xu, Zhi-Qiao] Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, No.85 Hedao Street, Longting District, 475001 Kaifeng, Henan, China.
RP Xu, ZQ (reprint author), Kaifeng Central Hospital, The Center of Tumor Diagnosis and Treatment, 475001 Kaifeng, China.
EM liningkfyy@163.com
CR Hu Y, Sun X, Mao C, et al, 2017, Upregulation of long noncoding RNATUG1 promotes cervical cancer cell proliferation and migration. Cancer Med 6(2):471–482
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 691
EP 696
DI 10.1007/s12253-018-0541-2
PG 6
ER
PT J
AU Li, D
Jiang, Y
Yang, W
AF Li, Ding
Jiang, Yunhui
Yang, Wan
TI Approach the Invasive Potential with Hurthle Cell Tumors of Thyroid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hurthle cell tumors; Immunohistochemistry; P53; CyclinD1; Ki-67
ID Hurthle cell tumors; Immunohistochemistry; P53; CyclinD1; Ki-67
AB To observe the expression of P53, CyclinD1, Ki-67, Galectin-3, COX-2, Bcl-2 and approach their contribution on assessing the invasive potential for Hurthle cell tumors. Seventy-three cases of Hurthle cell tumor were collected for immunohistochemistry staining. The patients were followed up with 8 months to 5 years. Tumors were divided into four grades according to invasion and diameter:(1) extremely low risk (27 cases that less than 2 cm and without invasion), (2) low risk (18 cases that within 2–3.9 cm and without invasion), (3) moderate risk (21 cases that achieve 4 cm and without invasion), (4) high risk (7 cases that with invasion of capsule/vessel in spite of the diameter). Immunostaining presented that all 73 cases were positive with Galectin-3, COX-2 and Bcl-2. For each group, P53 positive were 29.6%, 55.6%, 90.5%, 100.0%; CyclinD1 stained with 7.4%,22.2%,52.4%,100.0% and Ki-67 were 0.0%,5.6%,9.5%,28.6%, respectively. The higher risk of tumor, the more cases that positive expressed P53 and CyclinD1. After following up within 49 patients, two of the recurring cases were positive with P53 and CyclinD1 and one of which was also highly expressed Ki-67. Detecting P53, CyclinD1 and Ki-67 might provide reference for invasive potential assessment with Hurthle cell tumors but not Galectin-3, COX-2 and Bcl-2.
C1 [Li, Ding] the First People’s Hospital of Jingmen, Department of Pathology, 448000 Jingmen, Hubei Province, China.
[Jiang, Yunhui] the Second People’s Hospital of Jingmen, Department of Pathology, 448000 Jingmen, Hubei Province, China.
[Yang, Wan] the First People’s Hospital of Jingmen, Department of Pathology, 448000 Jingmen, Hubei Province, China.
RP Li, D (reprint author), the First People’s Hospital of Jingmen, Department of Pathology, 448000 Jingmen, China.
EM dl789521@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 697
EP 701
DI 10.1007/s12253-018-0546-x
PG 5
ER
PT J
AU Qin, L
Luo, JZ
Tang, XL
Han, ChG
AF Qin, Lu
Luo, Jin-Zhu
Tang, Xue-Lian
Han, Chuan-Gang
TI Identification of Long Noncoding RNA MIR22HG as a Novel Biomarker in Thyroid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid cancer; MIR22HG; Long non-coding RNA; Bioinformatics analysis; Biomarker
ID Thyroid cancer; MIR22HG; Long non-coding RNA; Bioinformatics analysis; Biomarker
AB Thyroid cancer (TC) is the one of the most common endocrine malignancy. However, currently there are no specific and sensitive biomarkers for predicting the prognosis for TC. In this study, we for the first time showed MIR22HG was down-regulated in thyroid cancer by analyzing public datasets, including TCGA, GSE29265, GSE33630, and GSE55091. Furthermore, we observed the lower expression levels of MIR22HG were significantly related to higher age, lymph node metastasis status, residual tumor status, N stage, Grade, and T stage in TC. We also observed higher MIR22HG expression was associated with longer overall and disease-free survival time in TC. In order to explore the potential mechanisms of MIR22HG regulating TC progression, 4 hub gene networks regulated by MIR22HG were constructed in the present study. Bioinformatics analysis showed MIR22HG was associated with apoptotic process, regulation of transcription, mRNA splicing, regulation of cell cycle, and Hippo signaling pathway in TC. These results suggested MIR22HG could serve as a novel biomarker for thyroid cancer.
C1 [Qin, Lu] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Thyroid Vascular Surgery, 430200 Jingzhou, Hubei, China.
[Luo, Jin-Zhu] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Clinical Laboratory, 430200 Jingzhou, Hubei, China.
[Tang, Xue-Lian] Yangtze University, The Second Clinical Medical College, Jingzhou Central Hospital, Department of Respiratory Medicine, 430200 Jingzhou, Hubei, China.
[Han, Chuan-Gang] The First People’s Hospital of Jiangxia District Wuhan City, Department of Anesthesiology, No. 1, Zhifang Culture Avenue, Jiangxia District, 430200 Wuhan, Hubei, China.
RP Han, ChG (reprint author), The First People’s Hospital of Jiangxia District Wuhan City, Department of Anesthesiology, 430200 Wuhan, China.
EM 34826551@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 703
EP 710
DI 10.1007/s12253-018-0521-6
PG 8
ER
PT J
AU Nasri, S
Humara, B
Anjomshoaa, A
Moradi, N
Gholipour, N
Mashjoor, S
Zhang, P
AF Nasri, Soroush
Humara, Bostjan
Anjomshoaa, Ahmad
Moradi, Nourodin
Gholipour, Naghmeh
Mashjoor, Sakineh
Zhang, Peng
TI Early Hereditary Diffuse Gastric Cancer (eHDGC) is Characterized by Subtle Genomic Instability and Active DNA Damage Response Soroush
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Genomic instability; Diffuse gastric cancer; Array CGH; DNA fragility
ID Genomic instability; Diffuse gastric cancer; Array CGH; DNA fragility
AB Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Chromosomal aberrations in early intramucosal hereditary diffuse gastric cancer (eHDGC) were assessed using array comparative genomic hybridization (array CGH). Notably, no aneuploidy or other large-scale chromosomal rearrangements were detected. Instead, all aberrations affected small regions (< 4.8 Mb) and were predominantly deletions. Analysis of DNA sequence patterns revealed that essentially all aberrations possessed the characteristics of common fragile sites. These results and the results of subsequent immunohistochemical examinations demonstrated that unlike advanced DGC, eHDGCs is characterized by low levels of genomic instability at fragile sites. Furthermore, they express an active DNA damage response, providing a molecular basis for the observed indolence of eHDGC. This finding is an important step to understanding the pathology underlying natural history of DGC and supports a revision of the current definition of eHDGC as a malignant disease.
C1 [Nasri, Soroush] University of Otago, Department of Biochemistry, Cancer Genetics Laboratory, 9054 Dunedin, New Zealand.
[Humara, Bostjan] University of Otago, Department of Biochemistry, Cancer Genetics Laboratory, 9054 Dunedin, New Zealand.
[Anjomshoaa, Ahmad] University of Otago, Department of Biochemistry, Cancer Genetics Laboratory, 9054 Dunedin, New Zealand.
[Moradi, Nourodin] Milad Center for Medical GeneticsSari, Iran.
[Gholipour, Naghmeh] Milad Center for Medical GeneticsSari, Iran.
[Mashjoor, Sakineh] Hormozgan University, Faculty of Marine Science and Technology, Department of Marine biologyBandar Abbas, Iran.
[Zhang, Peng] Australian National University, ANU College of Medicine, Biology and Environment, Research School of Biology, Division of Biomedical Science and BiochemistryCanberra, Australia.
RP Gholipour, N (reprint author), Milad Center for Medical Genetics, Sari, Iran.
EM ngholipour@nigeb.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 711
EP 721
DI 10.1007/s12253-018-0547-9
PG 11
ER
PT J
AU Park, YJ
Hong, GyD
Chong, OG
Park, YJ
AF Park, Young Ji
Hong, Gy Dae
Chong, Oh Gun
Park, Y Ji
TI Tumor Budding is a Valuable Diagnostic Parameter in Prediction of Disease Progression of Endometrial Endometrioid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial endometrioid carcinoma; Tumor budding; Prognosis; Lymphovascular invasion; Lymph node involvement
ID Endometrial endometrioid carcinoma; Tumor budding; Prognosis; Lymphovascular invasion; Lymph node involvement
AB Recently, tumor budding (TB) found at the invasive margin has been related to lymph node involvement (LNI), local recurrence, and poor prognosis in various cancers. We assessed the presence of TB in endometrial endometrioid carcinoma (EEC), and examined the immunohistochemical (IHC) profiles to define its clinicopathological significance. Ninety-six EECs were obtained from 2008 to 2013. During the follow-up, ten patients experienced disease progression; of these, three patients succumbed to the disease. All hematoxylin and eosin-stained slides were scrutinized for the presence of TB. IHC stainings for estrogen receptor (ER), progesterone receptor (PR), β-catenin, and E-cadherin were performed. All cases were grouped as FIGO grade (G) 1 (47.9%), G2 (29.2%), and G3 (22.9%). The distribution for depth of invasion (DOI) was 68.5% with a DOI of less than half and 31.5% with a DOI of more than half. Myometrial invasion was characterized as infiltrating pattern (52.1%), adenomyosis-like (20.8%), microcystic, elongated, and fragmented (17.7%), or expansile (9.4%). TB was identified in 63 cases (65.6%). Lymphovascular invasion (LVI) and LNI were identified in 47 and 37 cases, respectively. TB was associated with deep DOI (p = 0.001), higher FIGO grade (p = 0.006), LVI (p < 0.0001), and LNI (p < 0.0001). TB showed loss of ER (p < 0.0001) and PR (p < 0.0001), reduced E-cadherin (p < 0.0001) expression, and aberrant β-catenin expression (p = 0.042). In EECs, TB was associated with deep DOI, less-differentiated histology, frequent LVI, and LNI; furthermore, TB was closely related to epithelial-mesenchymal transition phenotype and downregulation of hormonal receptors. Therefore, TB might be a determinant histologic clue for prediction of disease progression in EECs.
C1 [Park, Young Ji] Kyungpook National University, School of Medicine, Chilgok Hospital, Department of PathologyDaegu, South Korea.
[Hong, Gy Dae] Kyungpook National University, School of Medicine, Chilgok Hospital, Department of Obstetrics and GynecologyDaegu, South Korea.
[Chong, Oh Gun] Kyungpook National University, School of Medicine, Chilgok Hospital, Department of Obstetrics and GynecologyDaegu, South Korea.
[Park, Y Ji] Kyungpook National University, School of Medicine, Chilgok Hospital, Department of PathologyDaegu, South Korea.
RP Park, YJ (reprint author), Kyungpook National University, School of Medicine, Chilgok Hospital, Department of Pathology, Daegu, South Korea.
EM pathpjy@naver.co.kr
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Euscher E, Fox P, Bassett R, al-Ghawi H, Ali-Fehmi R, Barbuto D, Djordjevic B, Frauenhoffer E, Kim I, Hong SR, Montiel D, Moschiano E, Roma A, Silva E, Malpica A, 2013, The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma. Amer J Surg Pathol 37(11):1728–1736
Choi HJ, Park KJ, Shin JS, Roh MS, Kwon HC, Lee HS, 2007, Tumor budding as a prognosticmarker in stage-III rectal carcinoma. Int J Color Dis 22(8):863–868
Kanazawa H, Mitomi H, Nishiyama Y, Kishimoto I, Fukui N, Nakamura T, Watanabe M, 2008, Tumour budding at invasive margins and outcome in colorectal cancer. Color Dis 10(1):41–47
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Hanekamp EE, Kuhne EC, Smid-Koopman E et al, 2002, Loss of progesterone receptor may lead to an invasive phenotype in human endometrial cancer. Eur J Cancer 38(Suppl 6):S71–S72
Hanekamp EE, Gielen SC, Smid-Koopman E, Kuhne LC, de Ruiter PE, Chadha-Ajwani S, Brinkmann AO, Grootegoed JA, Burger CW, Huikeshoven FJ, Blok LJ, 2003, Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer. Clin Cancer Res 9(11):4190–4199
Huang B, Cai J, Xu X, Guo S, Wang Z, 2016, High-grade tumor budding stratifies early-stage cervical Cancer with recurrence risk. PLoS One 11(11):e0166311
Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WEE, Paz-Ares L, Storkel S, Schumacher KM, von Heydebreck A, Celik I, O'Byrne KJ, 2012, EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13(1):33–42
Neubauer NL, Lurain JR, 2011, The role of lymphadenectomy in surgical staging of endometrial cancer. Int J Surg Oncol 2011: 814649
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Zhang C,Wang C, FengW, 2012, Clinicopathological risk factors for pelvic lymph node metastasis in clinical early-stage endometrioid endometrial adenocarcinoma. Int J Gynecol Cancer 22(8):1373–1377
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Stewart CJ, 2013, Epithelial-to-mesenchymal transition in endometrioid adenocarcinoma of the endometrium. Hum Pathol 44(9):1956–1957
Colas E, Pedrola N, Devis L, Ertekin T, Campoy I, Martinez E, Llaurado M, Rigau M, Olivan M, Garcia M, Cabrera S, Gil- Moreno A, Xercavins J, Castellvi J, Garcia A, Ramon y Cajal S, Moreno-Bueno G, Dolcet X, Alameda F, Palacios J, Prat J, Doll A, Matias-Guiu X, Abal M, Reventos J, 2012, The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol 14(10): 715–720
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van der Horst PH,Wang Y, Vandenput I, Kuhne LC, Ewing PC, van IJckenWFJ, van der Zee M, Amant F, Burger CW, Blok LJ, 2012, Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer. PLoS One 7(1):e30840
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 723
EP 730
DI 10.1007/s12253-018-0554-x
PG 8
ER
PT J
AU Zimpfer, A
Schneider, B
Blanck, O
Riedel, K
Zhivov, A
Jonigk, D
Erbersdobler, A
Junemann, A
Andratschke, N
Hildebrandt, G
Guthoff, FR
Kakkassery, V
AF Zimpfer, Annette
Schneider, Bjoern
Blanck, Oliver
Riedel, Katrin
Zhivov, Andrey
Jonigk, Danny
Erbersdobler, Andreas
Junemann, Anselm
Andratschke, Nicolaus
Hildebrandt, Guido
Guthoff, F Rudolf
Kakkassery, Vinodh
TI Pathologic Features of Tumor Activity and Stability in Uveal Melanoma Specimens after Fractionated CyberKnife Radiosurgery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uveal melanoma; CyberKnife; Stereotactic radiosurgery; Proliferation index; DNA image cytometry
ID Uveal melanoma; CyberKnife; Stereotactic radiosurgery; Proliferation index; DNA image cytometry
AB To evaluate uveal melanoma cell activity and pathologic features after stereotactic CyberKnife radiosurgery in specimens from five patients. Specimens from five patients treated by CyberKnife radiosurgery in three fractions were included in this study. Because of persistent retinal detachment in 3 patients, tumour endoresection was performed at four, seven and ten month after CyberKnife radiosurgery. At nine and twelve months after treatment, enucleation of the eye globe was performed in 2 patients because of secondary tumour bleeding and missing regression. After histomorphological analysis and determination of Ki67-proliferation index, DNA cytophotometry, fluorescence in-situ hybridization evaluation for chromosome 3 loss, GNA11and GNAQ mutation analysis were performed. Four of the five tumours included in this study showed variable radiation-induced morphologic changes in the form of enlargement of cells and nuclei, cytoplasmic vacuolisation and nuclear fragmentation. The DNA content of a large fraction of tumour cells was hypoploid. On the other hand, single strikingly hyperchromatic melanoma cells showed marked aneuploidy. The proliferation fraction in the three endoresected tumours was very low (<1%), but it was elevated in the enucleation cases. Monosomy 3 was detected in two of the endoresection cases, but none of the enucleation cases. None of the patients experienced a local tumour recurrence, but two of the patients developed liver metastasis. Many melanoma cells seemed to be vital within the first 6 months after CyberKnife radiosurgery, but obvious radiation-induced morphologic changes, including tumour necrosis, hypoploid DNA content plus low Ki-67 index could indicate sublethal cell damage.
C1 [Zimpfer, Annette] University Medicine Rostock, Institute of Pathology, Strempelstr. 14, 18057 Rostock, Germany.
[Schneider, Bjoern] University Medicine Rostock, Institute of Pathology, Strempelstr. 14, 18057 Rostock, Germany.
[Blanck, Oliver] University Medical Center Schleswig-Holstein, Department for Radiation Oncology, Arnold-Heller-Str. 3, 24105 Kiel, Germany.
[Riedel, Katrin] University Medicine Rostock, Department of Ophthalmology, Doberaner Str. 140, 18057 Rostock, Germany.
[Zhivov, Andrey] OSG MVZ Betriebs GmbH, Ophtalmology, OMS, Anesthetics, Buger Str, 82, 96049 Bamberg, Germany.
[Jonigk, Danny] Hannover Medical School, Institute of Pathology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
[Erbersdobler, Andreas] University Medicine Rostock, Institute of Pathology, Strempelstr. 14, 18057 Rostock, Germany.
[Junemann, Anselm] University Medicine Rostock, Department of Ophthalmology, Doberaner Str. 140, 18057 Rostock, Germany.
[Andratschke, Nicolaus] University Hospital Zurich, Department of Radiation Oncology, Ramistr. 100, 8091 Zurich, Switzerland.
[Hildebrandt, Guido] University Medical Center Rostock, Department of Radiotherapy, Sudring 75, 18059 Rostock, Germany.
[Guthoff, F Rudolf] University Medicine Rostock, Department of Ophthalmology, Doberaner Str. 140, 18057 Rostock, Germany.
[Kakkassery, Vinodh] University Medicine Rostock, Department of Ophthalmology, Doberaner Str. 140, 18057 Rostock, Germany.
RP Zimpfer, A (reprint author), University Medicine Rostock, Institute of Pathology, 18057 Rostock, Germany.
EM annette.zimpfer@med.uni-rostock.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 731
EP 740
DI 10.1007/s12253-018-00565-1
PG 10
ER
PT J
TI Relationship Between -2028 C/T SELP Gene Polymorphism, Concentration of Plasma P-Selectin and Risk of Malnutrition in Head and Neck Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Malnutrition; Cachexia; Head and neck cancer; SELP; P-selectin
ID Malnutrition; Cachexia; Head and neck cancer; SELP; P-selectin
AB Until today there is a lack of molecular factors, that could predict either cancer malnutrition or cachexia. Among potential mechanisms, that contribute to development of above syndromes, the systemic inflammatory response with overproduction of cytokines and adhesion molecules is the most likely. Recent papers suggested crucial role of P-selectin adhesion molecule in the initiation of leukocytes recruitment to the site of injury during inflammation, promotion of tumor aggressiveness and contribution to cancer cachexia. The aim of the study was to investigate SELP -2028 C/T polymorphism as a risk factor of malnutrition in 66 head and neck cancer (HNC) patients subjected to radiotherapy. Genotyping was conducted by real-time PCR method by means of TaqMan SNP Genotyping Assay. P-selectin Human ELISA Kit was used to determine P-selectin concentration in each extracted plasma samples. CC homozygous subjects had 4-fold higher risk score of being qualified as severely malnourished compared to other genotype carriers (p = 0.015). However, the TT homozygous patients were at lowest risk of severe weight loss >10% during the therapy period (OR = 0.20; p = 0.019).We also noted, that CC genotype carriers had significantly higher risk of early death incidence compared to CT or TT genotype (median survival time: 29 vs 34 months; HR = 3.02; p = 0.0085). Studied SELP -2028 C/T seems to be a novel attractive predictive factor of cancer malnutrition in HNC patients, perhaps in a future, patients carrying unfavorable CC genotype could be earlier scheduled for pharmaceutical intervention with parenterall nutrition, therefore they could be prevented from the development of severe malnutrition or even cachexia.
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Burkhardt J, Blume M, Petit-Teixeira E, Hugo Teixeira V, Steiner A, Quente E, Wolfram G, Scholz M, Pierlot C, Migliorini P, Bombardieri S, Balsa A, Westhovens R, Barrera P, Radstake TRDJ, Alves H, Bardin T, Prum B, Emmrich F, Cornelis F, Ahnert P, Kirsten H, 2014, Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression. PLoS One 9(8):e103872
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Johns N, Stretch C, Tan BHL, 2017, New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss. J Cachexia Sarcopenia Muscle 8(1):122–130
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 741
EP 749
DI 10.1007/s12253-018-00578-w
PG 9
ER
PT J
AU Aydin, AH
Toptas, T
Bozkurt, S
Aydin, A
Erdogan, G
Pestereli, E
Simsek, T
AF Aydin, Ayik Hulya
Toptas, Tayfun
Bozkurt, Selen
Aydin, Armagan
Erdogan, Gulgun
Pestereli, Elif
Simsek, Tayup
TI Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Stanniocalcin-2; Endometrial cancer; Prognostic factor; Recurrence
ID Stanniocalcin-2; Endometrial cancer; Prognostic factor; Recurrence
AB In the current study, we primarily aimed to investigate stanniocalcin-2 (STC2) protein expression pattern in hysterectomy specimens from patientswith endometrioid type endometrial cancer (EC) using immunohistochemistry. Secondly, in order to clarify its prognostic impact, we examined relationships of the expression levels of STC2 with clinicopathologic features and outcome of patients. Histopathology slides of 49 patients were stained with the monoclonal mouse antibody targeting STC2 protein. The expression levels of STC2 were classified based on three-tiered semiquantitative scheme: negative expression, expression level of 0; low-expression, expression level of 1+; and high-expression, expression levels of 2+ and 3+. Recurrence-free survival (RFS) was used as the primary prognostic outcome. Immunohistochemical analysis revealed that 73.5% of tissue samples exhibited positive staining with STC2. The intensity of staining with STC2 was weak in 40.8%, moderate in 22.4%, and strong in 10.2%. Thirty-eight percent of samples showed negative expression; 18.4%, low-expression (1+); and 42.8%, high-expression (2 to 3+). High-expression of STC2 was significantly associated with grade 2–3 tumors (p = 0.026) and disease recurrence (p = 0.013). Multivariate analysis revealed that both the tumor grade and STC2 were independent predictors of disease recurrence. Kaplan-Meier analyses confirmed that patients with highexpression of STC2 had a significantly poorer RFS than those with negative or low STC2 expression (p = 0.037); although overall survival did not differ with respect to expression levels of STC2 (p = 0.148). In conclusion, high-expression of STC2 is a negative prognostic factor, associated with increased risk of recurrence in endometrioid EC.
C1 [Aydin, Ayik Hulya] Akdeniz University, School of Medicine, Department of Gynecologic Oncology, Dumlupinar Boulevard, H-Block, K:1, Konyaalti, 07059 Antalya, Turkey.
[Toptas, Tayfun] Antalya Training and Research Hospital, Department of Gynecologic OncologyAntalya, Turkey.
[Bozkurt, Selen] Akdeniz University, School of Medicine, Department of Biostatistics and Medical InformaticsAntalya, Turkey.
[Aydin, Armagan] Antalya Research and Training Hospital, Antalya, Department of Medical OncologyAntalya, Turkey.
[Erdogan, Gulgun] Akdeniz University, School of Medicine, Department of Gyneco-pathologyAntalya, Turkey.
[Pestereli, Elif] Akdeniz University, School of Medicine, Department of Gyneco-pathologyAntalya, Turkey.
[Simsek, Tayup] Akdeniz University, School of Medicine, Department of Gynecologic Oncology, Dumlupinar Boulevard, H-Block, K:1, Konyaalti, 07059 Antalya, Turkey.
RP Aydin, AH (reprint author), Akdeniz University, School of Medicine, Department of Gynecologic Oncology, 07059 Antalya, Turkey.
EM hulya_ayik@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 751
EP 757
DI 10.1007/s12253-018-00576-y
PG 7
ER
PT J
AU da Silva Filho, FA
Vieira-de-Mello, SG
Santos, BdP
de Melo Rego, JBM
Ribeiro-Silva, A
Beltrao, ICE
AF da Silva Filho, Felix Antonio
Vieira-de-Mello, Souto Gabriela
Santos, Barros dos Petra
de Melo Rego, Jesus Barreto Moacyr
Ribeiro-Silva, Alfredo
Beltrao, Isidoro Carneiro Eduardo
TI N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glycosiltranferases; Glycocode; Lectins; In situ ductal carcinoma; Invasive ductal carcinoma
ID Glycosiltranferases; Glycocode; Lectins; In situ ductal carcinoma; Invasive ductal carcinoma
AB Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide Nacetylgalactosaminyltransferase- 6 (ppGalNAc-T6), −T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.
C1 [da Silva Filho, Felix Antonio] Federal University of Pernambuco, Immunomodulation and New Therapeutic Approaches Laboratory, 50670-901 Recife, Pernambuco, Brazil.
[Vieira-de-Mello, Souto Gabriela] Federal University of Pernambuco, Immunomodulation and New Therapeutic Approaches Laboratory, 50670-901 Recife, Pernambuco, Brazil.
[Santos, Barros dos Petra] Federal University of Pernambuco, Biomarkers in cancer Laboratory, 50670-901 Recife, Pernambuco, Brazil.
[de Melo Rego, Jesus Barreto Moacyr] Federal University of Pernambuco, Immunomodulation and New Therapeutic Approaches Laboratory, 50670-901 Recife, Pernambuco, Brazil.
[Ribeiro-Silva, Alfredo] University of Sao Paulo, Faculty of Medicine of Ribeirao Preto, Department of Pathology, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
[Beltrao, Isidoro Carneiro Eduardo] Federal University of Pernambuco, Biomarkers in cancer Laboratory, 50670-901 Recife, Pernambuco, Brazil.
RP de Melo Rego, JBM (reprint author), Federal University of Pernambuco, Immunomodulation and New Therapeutic Approaches Laboratory, 50670-901 Recife, Brazil.
EM moacyr.rego@gmail.com
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Rego MJBM, Vieira de Mello GS, da Silva Santos CA, Chammas R, Beltrao EIC, 2013, Implications on glycobiological aspects of tumor hypoxia in breast ductal carcinoma in situ. Med Mol Morphol 46:92–96. , DOI 10.1007/s00795-013-0013-4
Abbott KL, Aoki K, Lim JM, Porterfield M, Johnson R, O'Regan RM, Wells L, Tiemeyer M, Pierce M, 2008, Targeted glycoproteomic identification of biomarkers for human breast carcinoma. J Proteome Res 7:1470–1480. , DOI 10.1021/ pr700792g
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 759
EP 768
DI 10.1007/s12253-019-00593-5
PG 10
ER
PT J
AU Jin, J
Guo, Q
Xie, J
Jin, D
Zhu, Y
AF Jin, Jianying
Guo, Qunyi
Xie, Jingjing
Jin, Dan
Zhu, Yanan
TI Combination of MEK Inhibitor and the JAK2-STAT3 Pathway Inhibition for the Therapy of Colon Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MEK inhibitors; Colon cancer; JAK2; STAT3
ID MEK inhibitors; Colon cancer; JAK2; STAT3
AB The study aimed to investigate the reason of HCT116 cell resistance to MEK inhibitor, and the combination treatment effects of MEK inhibitor AZD6244 and JAK2/STAT3 inhibitor AG490 on colon cancer in vitro and in vivo, including cell viability, apoptosis, and explore the partial mechanisms focused on AZD6244 promoted the activation of JAK2-STAT3 pathways. In vitro, we examined the HCT116 cell viability by CCK8, cell apoptosis by flow cytometry;Western blot measured p-ERK, p-JAK2, p- STAT3 and STAT3 expression. In vivo, nude mice were subcutaneously injected by HCT116 cells. The tumor volume and weight were detected. HCT116 cell resistance to MEK inhibitor AZD6244, which inhibited the activation of ERK and promoted the activation of JAK2-STAT3 signaling. The combination treatment of AZD6244 and AG490 significantly inhibited cell viability and induced cell apoptosis, and completely inhibited the activation of ERK and JAK2-STAT3 signaling. Combination treatment of AZD6244 and AG490 had a stronger effect than that of AZD6244 as a monotherapy in vitro and in vivo. The treatment of AZD6244 on K-Ras mutations HCT116 cells promoted the activation of JAK2/STAT3 signaling. JAK2/STAT3 inhibitor AG490 synergistically increases effects of AZD6244 on colon cancer in vitro and in vivo. Collectively, these results provide a rationale for combining inhibitors of the JAK/STAT pathway and MEK inhibitors to reduce the potential impact of drug resistance.
C1 [Jin, Jianying] Taizhou Hospital, Department of Blood Oncology, 318000 Taizhou, China.
[Guo, Qunyi] Taizhou Hospital, Department of Blood Oncology, 318000 Taizhou, China.
[Xie, Jingjing] Taizhou Hospital, Department of Blood Oncology, 318000 Taizhou, China.
[Jin, Dan] Taizhou Hospital, Department of Blood Oncology, 318000 Taizhou, China.
[Zhu, Yanan] Emergency Center of Taizhou Hospital, 318000 Taizhou, China.
RP Zhu, Y (reprint author), Emergency Center of Taizhou Hospital, 318000 Taizhou, China.
EM 13736248866@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 769
EP 775
DI 10.1007/s12253-019-00592-6
PG 7
ER
PT J
AU Kar, S
Majumder, DD
AF Kar, Subrata
Majumder, Dutta Dwijesh
TI A Novel Approach of Mathematical Theory of Shape and Neuro-Fuzzy Based Diagnostic Analysis of Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Pap smear images segmentation; Features extraction; Shape theory; Neuro-fuzzy classification system
ID Cervical cancer; Pap smear images segmentation; Features extraction; Shape theory; Neuro-fuzzy classification system
AB This study aims to detect the abnormal growth of tissue in cervix region for diagnosis of cervical cancer using Pap test of patients. The proposed methodology classifies cervical cancer for pattern recognition either benign or malignant stages using shape and neuro-fuzzy based diagnostic model. In this experiment, firstly the authors segment Pap smear images of cervical cells using fuzzy c-means clustering algorithm and shape theory to classify them according to the presence of abnormality of the cells. Secondly the features extraction process is performed in the part of nucleus and cytoplasm on the squamous and glandular cells and the authors used input variables such as cytoplasm area (CA), cytoplasm circularity (CC), nucleus area (NA), nucleus circularity (NC), nucleus-cytoplasm ratio (NCR), and maximum nucleus brightness (MNB) in fuzzy tools and used fuzzy rules to evaluate the cervical cancer risk status as an output variable. The proposed neuro-fuzzy network system was developed for early detection of cervical cancer. A neural network was trained with 15-Pap image datasets where Levenberg–Marquardt(LM) a feed-forward back-propagation algorithmwas used to get the status of the cervical cancer. Out of 15 samples database, 11 data set for training, 2 data set for validation and 2 data set for test were used in the ANN classification system. The presented fuzzy expert system(FES) successfully identified the presence of cervical cancer in the Pap smear images using the extracted features and the use of neuro-fuzzy system(NFS) for the identification of cervical cancer at the early stages and achieve a satisfactory performance with 100% accuracy.
C1 [Kar, Subrata] Dumkal Institute of Engineering & Technology, Department of Mathematics, 742406 Murshidabad, West Bengal, India.
[Majumder, Dutta Dwijesh] Indian Statistical Institute, Department of Electronics and Communication Sciences Unit, 700108 Kolkata, West Bengal, India.
RP Kar, S (reprint author), Dumkal Institute of Engineering & Technology, Department of Mathematics, 742406 Murshidabad, India.
EM subrata.bacchu@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 777
EP 790
DI 10.1007/s12253-019-00582-8
PG 14
ER
PT J
AU Tan, L
Wu, Y
Ma, X
Yan, Y
Shao, Sh
Liu, J
Ma, H
Liu, R
Chai, L
Ren, J
AF Tan, Li
Wu, Yinying
Ma, Xiaowei
Yan, Yanli
Shao, Shuai
Liu, Jiaxin
Ma, Hailin
Liu, Rui
Chai, Linyan
Ren, Juan
TI A Comprehensive Meta-Analysis of Association between EGFR Mutation Status and Brain Metastases in NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epidermal growth factor receptor; NSCLC; Brain metastases; Meta-analysis
ID Epidermal growth factor receptor; NSCLC; Brain metastases; Meta-analysis
AB Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have different clinicopathological characteristics compared with EGFR wild type NSCLC. A growing number of studies focused on the relevance between EGFR mutation status and brain metastases (BM) in NSCLC, but it remains controversial. Therefore, this study performed a comprehensive meta-analysis to untangle this issue. Several electronic databases including Pubmed, Embase, Web of science and Cochrane database were thoroughly searched. The odds ratio (OR) with 95% confidence interval (95% CI) was pooled to evaluate the relevance. Meta-regression analysis and subgroup analysis were conducted according to the heterogeneity. A total of 26 studies were identified finally in this meta-analysis. The overall OR was 1.58 (95% CI: 1.36–1.84), which indicated that EGFR mutation had a positive association with BM of NSCLC. The subgroup analysis resulted from eleven studies with lung adenocarcinoma revealed a higher possibility of BM in NSCLC with EGFR mutation compared with EGFR wild (p < 0.05). There was no significant difference in the risk of BM between NSCLC EGFR exon 19 mutation and exon 21 point mutation (p = 0.23). This meta-analysis suggests that EGFR mutation can be a risk factor for BM in NSCLC.
C1 [Tan, Li] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi, China.
[Wu, Yinying] First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical Oncology, 710061 Xi’an, Shaanxi, China.
[Ma, Xiaowei] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi, China.
[Yan, Yanli] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi, China.
[Shao, Shuai] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi, China.
[Liu, Jiaxin] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi, China.
[Ma, Hailin] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi, China.
[Liu, Rui] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi, China.
[Chai, Linyan] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi, China.
[Ren, Juan] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi, China.
RP Ren, J (reprint author), First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, China.
EM 869491533@qq.com
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Arora S, Ranade AR, Tran NL, Nasser S, Sridhar S, Korn RL, Ross JT, DhruvH, FossKM, Sibenaller Z, Ryken T, Gotway MB,Kim S,Weiss GJ, 2011, MicroRNA-328 is associated with, non-small, cell lung cancer, NSCLC, brain metastasis and mediates NSCLC migration. Int J Cancer 129(11):2621–2631. , DOI 10.1002/ijc.25939
Yoo JY, Yang SH, Lee JE, Cho DG, Kim HK, Kim SH, Kim IS, Hong JT, Sung JH, Son BC, 2012, E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model. J Neuro-Oncol 109(2):219–227
Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW, 2003, Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284(1):31–53
Dearden S, Stevens J, Wu YL, Blowers D, 2013, Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology, mutMap). Annals Oncol 24(9):2371– 2376
Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM, Johnson BE, 2010, Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res 16(23):5873–5882. , DOI 10.1158/1078- 0432.ccr-10-1588
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Singh M, Garg N, Venugopal C, Hallett R, Tokar T, McFarlane N, Mahendram S, Bakhshinyan D, Manoranjan B, Vora P, Qazi M, Arpin CC, Page B, Haftchenary S, Rosa DA, Lai PS, Gomez- Biagi RF, Ali AM, Lewis A, Geletu M, Murty NK, Hassell JA, Jurisica I, Gunning PT, Singh SK, 2015, STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR- 21 activation. Oncotarget 6(29):27461–27477. , DOI 10. 18632/oncotarget.4742
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Pottgen C, EberhardtW, Grannass A, Korfee S, Stuben G, Teschler H, Stamatis G, Wagner H, Passlick B, Petersen V, Budach V, Wilhelm H, Wanke I, Hirche H, Wilke HJ, Stuschke M, 2007, Prophylactic cranial irradiation in operable stage IIIA non smallcell lung cancer treated with neoadjuvant chemoradiotherapy: results from a German multicenter randomized trial. J Clin Oncol 25(31):4987–4992. , DOI 10.1200/jco.2007.12.5468
Gore EM,BaeK,Wong SJ, SunA, Bonner JA, Schild SE,GasparLE, Bogart JA, Werner-Wasik M, Choy H, 2011, Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol 29(3): 272–278. , DOI 10.1200/jco.2010.29.1609
Dimitropoulos C, Hillas G, Nikolakopoulou S, Kostara I, Sagris K, Vlastos F, Alchanatis M, 2011, Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates? Cancer Manag Res:287–294
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 791
EP 799
DI 10.1007/s12253-019-00598-0
PG 9
ER
PT J
AU Sipka, S
Brugos, B
Czifra, G
Griger, Z
Balogh, N
Tarr, T
Papp, G
Biro, T
Zeher, M
AF Sipka, Sandor
Brugos, Boglarka
Czifra, Gabriella
Griger, Zoltan
Balogh, Norbert
Tarr, Tunde
Papp, Gabor
Biro, Tamas
Zeher, Margit
TI Season Dependent Changes in the Expression of Protein Kinase C Isoenzymes in a Female Patient with Systemic Lupus Erythematosus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE European white women; Peripheral blood mononuclear cells (PBMC); Protein kinase C (PKC); Season dependence; Systemic lupus erythematosus (SLE)
ID European white women; Peripheral blood mononuclear cells (PBMC); Protein kinase C (PKC); Season dependence; Systemic lupus erythematosus (SLE)
AB We aimed to answer the question whether the decreased expression of protein kinase C (PKC) isoenzymes in the peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) is inherited or not. For this reason we examined the expression of PKC isoenzymes in a European white girl with acute SLE and in her healthy mother and father simultaneously in summer and winter during one year using western blotting and densitometry. We found that in the father the expression of PKC isoenzymes did not differ from that of eight healthy controls included women and men. However, in the "SLE-free" mother and in the patient arrived in July with acute symptoms of lupus, the expression of PKC isoenzymes showed a season dependent undulation in parallel. Namely, in summer the expression values were significantly lower, in winter they were significantly higher than those in the controls. Thus, the decreased expression of PKC isoenzymes in the PBMC of SLE patient is not a disease specific marker; it appears also in her lupus free mother. This phenomenon may be due to a season dependent female genetic background. However, the low PKC levels in summer can still decrease further the low production of IL-2 in T cells of lupus patients augmenting the existing AP-1 defects. This is the first report on the season and female dependent inherited changing of PKC expression in a European white patient with SLE and her mother. Further studies are needed to confirm these findings in other populations.
C1 [Sipka, Sandor] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
[Brugos, Boglarka] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
[Czifra, Gabriella] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei blvd, 98, H-4032 Debrecen, Hungary.
[Griger, Zoltan] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
[Balogh, Norbert] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei blvd, 98, H-4032 Debrecen, Hungary.
[Tarr, Tunde] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
[Papp, Gabor] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
[Biro, Tamas] University of Debrecen, Faculty of Medicine, Department of Physiology, Nagyerdei blvd, 98, H-4032 Debrecen, Hungary.
[Zeher, Margit] University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, Moricz Zs. str. 22, H-4032 Debrecen, Hungary.
RP Sipka, S (reprint author), University of Debrecen, Faculty of Medicine, Division of Clinical Immunology, H-4032 Debrecen, Hungary.
EM sipka@iiibel.dote.hu
CR Biro T, Griger Z, Kiss E, Papp H, Aleksza M, Kovacs I, Zeher M, Bodolay E, Csepany T, Szucs K, Gergely P, Kovacs L, Szegedi G, Sipka S, 2004, Abnormal cell specific expression of certain protein kinase C isoenzymes in peripheral mononuclear cells of patients with systemic lupus erythematosus: effect of corticosteroid application. Scand J Immunol 60:421–442
Webster JR Moenter SM, Woodfill CJ, Karsch FJ, 1991, Role of the thyroid gland in seasonal reproduction. II. Thyroxine allows a season-specific suppression of gonadotropin secretion in sheep. Endocrinology 129:176–183
Cedeno S, Cifarelli DF, Blasini AM, Placeres F, Alonso G, Rodriguez MA, 2003, Defective activity of ERK-1 and ERK-2 mitogen activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus: potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells. Clin Immunol 106: 41–49
Gorelik G, Fang JY, Wu A, Sawalha AH, Richardson B, 2007, Impaired T cell protein kinase C delta activation decreases ERK pathway signalling in idiopathic and hydralazine induced lupus. J Immunol 179:5553–5563
Konya C, Paz Z, Tsokos GC, 2014, The role of T cells in systemic lupus erythematosus: an update. Curr Opin Rheumatol 26:493–501
Moulton VR, Tsokos GS, 2012, Why do women get lupus? Clin Immunol 144:53–56
McCuaig RD, Dunn J, Li J, Masch A, Knaute T, Schutkowski M, Zerweck J, Rao S, 2015, PKC-theta is a novel SC35 splicing factor regulator in response to Tcell activation. Front Immunol 6:562–576
Hughes GC, Choubey D, 2004, Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. Nat Rev Rheumatol 10:740–751
Panchanathan R, Shen H, Bupp MG, Gould KA, Choubey D, 2009, Female and male sex hormones differentially regulate expressions of lfi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval. J Immunol 183:7031–7038
Tesar V, Hruskova Z, 2015, Lupus nephritis: a different disease in European patients? Kidney Dis 1:110–118
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 801
EP 805
DI 10.1007/s12253-019-00591-7
PG 5
ER
PT J
AU Darre, T
Aboubakari, AS
N’Bortche, KB
Bassowa, A
Napo-Koura, G
AF Darre, Tchin
Aboubakari, Abdoul-Samadou
N’Bortche, K Bingo
Bassowa, Akila
Napo-Koura, Gado
TI Association of Schistosomiasis with Cervical Cancer in Togo: the Consequence of this Association
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Cervical cancer; Schistosomiasis; Carcinoma; HPV; Togo
ID Cervical cancer; Schistosomiasis; Carcinoma; HPV; Togo
AB Objective of the study was to determine the association of cervical cancer association and schistosomiasis infection. We conducted a retrospective and descriptive study of cases of cervical cancer and identified cases associated with schistosomiasis. A total of 1027 cases of cervical cancer were collected, and 19 cases revealed an association with schistosomiasis. This association was mainly related to squamous carcinoma with 18/19 cases. All patients were from rural areas. Of the 19 cases of association, 17 cases showed signs of HPV infection. Our data show a high degree of HPV infection that causes cervical cancer and not schistosomiasis.
C1 [Darre, Tchin] University Teaching Hospital of Lome, Department of PathologyLome, Togo.
[Aboubakari, Abdoul-Samadou] The University Teaching Hospital of Kara, Department Obstetrics and GynecologyKara, Togo.
[N’Bortche, K Bingo] The University Teaching Hospital of Lome, Department Obstetrics and GynecologyLome, Togo.
[Bassowa, Akila] The University Teaching Hospital of Lome, Department Obstetrics and GynecologyLome, Togo.
[Napo-Koura, Gado] University Teaching Hospital of Lome, Department of PathologyLome, Togo.
RP Darre, T (reprint author), University Teaching Hospital of Lome, Department of Pathology, Lome, Togo.
EM paolodarre@yahoo.fr
CR Plummer M, de Martel C, Vignat J et al, 2016, Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 4(9):e609–e616
Darre T, Kpatcha K, Tchaou M et al, 2015, Histological aspect of urinary schistosomiasis in Togo: results of a cohort of 192 cases. Bull Soc Pathol Exot 108(2):124–125
GayeAM, Doh K, ThiamI et al, 2016, Schistosomiasis and cancer: a fortuitous association or relationships cause and effect. Bull Cancer 103(9):806–807
Mandong BM, Ngbea JA, Raymond V, 2013, Role of parasites in cancer. Niger J Med 22(2):89–92
Riffenburgh RH, Olson PE, Johnstone PA, 1997, Association of schistosomiasis with cervical cancer: detecting bias in clinical studies. East Afr Med J 74(1):14–16
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 807
EP 808
DI 10.1007/s12253-017-0350-z
PG 2
ER
PT J
AU Stoyanov, G
Kitanova, M
Dzhenkov, D
Ghenev, P
AF Stoyanov, George
Kitanova, Martina
Dzhenkov, Deyan
Ghenev, Peter
TI The Diagnostic Dilemma of Epithelial Marker Expression in Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Stoyanov, George] Medical University - Varna Prof. Dr. Paraskev Stoyanov, Faculty of Medicine, Department of Anatomy and Cell BiologyVarna, Bulgaria.
[Kitanova, Martina] Medical University - Varna Prof. Dr. Paraskev Stoyanov, Faculty of Medicine, Department of General and Clinical Pathology, Forensic Medicine and DeontologyVarna, Bulgaria.
[Dzhenkov, Deyan] Medical University - Varna Prof. Dr. Paraskev Stoyanov, Faculty of Medicine, Department of General and Clinical Pathology, Forensic Medicine and DeontologyVarna, Bulgaria.
[Ghenev, Peter] Medical University - Varna Prof. Dr. Paraskev Stoyanov, Faculty of Medicine, Department of General and Clinical Pathology, Forensic Medicine and DeontologyVarna, Bulgaria.
RP Stoyanov, G (reprint author), Medical University - Varna Prof. Dr. Paraskev Stoyanov, Faculty of Medicine, Department of Anatomy and Cell Biology, Varna, Bulgaria.
EM georgi.geesh@gmail.com
CR Terada T, 2015, Expression of cytokeratins in glioblastoma multiforme. Pathol Oncol Res 21(3):817–819
Kriho VK, Yang HY,Moskal JR, Skalli O, 1997, Keratin expression in astrocytomas: an immunofluorescent and biochemical reassessment. Virchows Arch 431(2):139–147
Oh D, Prayson RA, 1999, Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study. Arch Pathol Lab Med 123(10):917–920
Stoyanov GS, Dzhenkov D, Ghenev P, 2017, Cytokeratin AE1/AE3 mimicry in glioblastoma. Script Sci Med 49(1):47-52
Stoyanov GS, Dzhenkov D, Ghenev P, 2017, The great imitator– EMA positive glioblastoma multiforme. Script Sci Med 49(1):21-25
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 809
EP 810
DI 10.1007/s12253-017-0354-8
PG 2
ER
PT J
AU Sabato, C
Bastos-Rodrigues, L
Chaves Moraes, D
Friedman, E
De Marco, L
Resende, V
AF Sabato, Cristina
Bastos-Rodrigues, Luciana
Chaves Moraes, Debora
Friedman, Eitan
De Marco, Luiz
Resende, Vivian
TI Genetic Analysis of Brazilian Patients with Gallbladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Sabato, Cristina] Universidade Federal de Minas Gerais, Department of Surgery, Av. Alfredo Balena 190, room 114, 30130-100 Belo Horizonte, Brazil.
[Bastos-Rodrigues, Luciana] Universidade Federal de Minas Gerais, Department of NutritionBelo Horizonte, Brazil.
[Chaves Moraes, Debora] Universidade Federal de Minas Gerais, Department of Surgery, Av. Alfredo Balena 190, room 114, 30130-100 Belo Horizonte, Brazil.
[Friedman, Eitan] Chaim Sheba Medical Center, The Susanne Levy Gertner Oncogenetics UnitTel-Hashomer, Israel.
[De Marco, Luiz] Universidade Federal de Minas Gerais, Department of Surgery, Av. Alfredo Balena 190, room 114, 30130-100 Belo Horizonte, Brazil.
[Resende, Vivian] Universidade Federal de Minas Gerais, Department of Surgery, Av. Alfredo Balena 190, room 114, 30130-100 Belo Horizonte, Brazil.
RP De Marco, L (reprint author), Universidade Federal de Minas Gerais, Department of Surgery, 30130-100 Belo Horizonte, Brazil.
EM ldemarco@ufmg.br;luiz.demarco@gmail.com
CR Bal MM, Ramadwar M, Deodhar K, Shrikhande S, 2015, Pathology of gallbladder carcinoma: current understanding and new perspectives. Pathol. Oncol. Res. 21:509–525
Jain K,Mohapatra T, Das P, MisraMC, Gupta SD, GhoshM, Kabra M, Bansal VK, Kumar S, Sreenivas V, Garg PK, 2014, Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer. Ann. Surg. 260:1073–1080
Espinoza JA, Bizama C, Garcia P, Ferreccio C, Javle M,Miquel JF, Koshiol J, Roa JC, 2016, The inflammatory inception of gallbladder cancer. Biochim. Biophys. Acta 1865:245–254
Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T, 2015, Genomic spectra of biliary tract cancer. Nat. Genet. 47:1003–1010
Bastos-Rodrigues L, Pimenta JR, Pena SD, 2006, The genetic structure of human populations studied through short insertiondeletion polymorphisms. Ann. Hum. Genet. 70:658–665
Serra S, 2014, Precursor neoplastic lesions of the biliary tract. J. Clin. Pathol. 67:875–882
Nagahashi M, Ajioka Y, Lang I, Szentirmay Z, Kasler M, Nakadaira H, Yokoyama N, Watanabe G, Nishikura K, Wakai T, Shirai Y, Hatakeyama K, Yamamoto M, 2008, Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary. World J. Gastroenterol. 14:70–75
Saetta AA, 2006, K-ras, p53 mutations, and microsatellite instability, MSI, in gallbladder cancer. J. Surg. Oncol. 93:644–649
Hanada K, Tsuchida A, Iwao T, Eguchi N, Sasaki T, Morinaka K, Matsubara K, Kawasaki Y, Yamamoto S, Kajiyama G, 1999, Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Am. J. Gastroenterol. 94:1638–1642
Bakos RM, Besch R, Zoratto GG, Godinho JM, Mazzotti NG, Ruzicka T, Bakos L, Santos SE, Ashton-Prolla P, Berking C, Giugliani R, 2011, The CDKN2A p.A148T variant is associated with cutaneous melanoma in southern Brazil. Exp. Dermatol. 20: 890–893
Soufir N, Ribojad M, Magnaldo T, Thibaudeau O, Delestaing G, Daya-Grosjean L, Rivet J, Sarasin A, Basset-Seguin N, 2002, Germline and somatic mutations of the INK4a-ARF gene in a xeroderma pigmentosum group C patient. J Invest Dermatol 119: 1355–1360
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 811
EP 814
DI 10.1007/s12253-018-0407-7
PG 4
ER
PT J
AU Wiwanitkit, V
AF Wiwanitkit, Viroj
TI Early Skin Rash and Cetuximab-Based Therapy of Advanced Biliary Tract Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Wiwanitkit, Viroj] Hainan Medical UniversityHaikou, China.
RP Wiwanitkit, V (reprint author), Hainan Medical University, Haikou, China.
CR RubovszkyG,BudaiB,GanofszkyE,HorvathZ,JuhosE,Madaras B,NagyT,SzaboE,PinterT,TothE,NagyP,LangI,HitreE(2017 Apr 29)Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer. Pathol Oncol Res. , DOI 10.1007/s12253-017-0238-y [Epubaheadof print]
Opneja A, Mahajan S, Kapoor S, Marur S, Yang SH, Manno R, 2015)Unusual Paraneoplastic Presentation of Cholangiocarcinoma.Case RepMed2015:806835
MacLean JD, Graeme-CookFM, 2002Apr 18)Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises.Case12-2002.A50-year-oldmanwith eosinophilia andfluctuatinghepaticlesions.NEnglJMed346(16):1232–1239
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 815
EP 815
DI 10.1007/s12253-018-0424-6
PG 1
ER
PT J
AU Stein, KM
Morris, KL
Martin, GM
AF Stein, K Matthew
Morris, K Lindsay
Martin, G Mike
TI JAK Pseudokinase Domain Variants Highlight nRTK VUSs Identified with Next-Generation Sequencing in Solid Tumor Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Stein, K Matthew] West Cancer CenterMemphis, TN, USA.
[Morris, K Lindsay] University of Tennessee, Health Science Center, College of MedicineMemphis, TN, USA.
[Martin, G Mike] West Cancer CenterMemphis, TN, USA.
RP Stein, KM (reprint author), West Cancer Center, Memphis, USA.
EM mkstein@westclinic.com
CR Lupardus PJ, Ultsch M, Wallweber H et al, 2014, Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase, JAK, autoinhibition. Proc Natl Acad Sci U S A 111:8025–8030
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, 2010, Sunyaev SR. NatMethods 7(4):248– 249
Cante-Barrett K, Uitdehaag JC, Meijerink JP, 2016, Structural modeling of JAK1 mutations in T-cell acute lymphoblastic leukemia reveals a second contact site between pseudokinase and kinase domains. Haematologica 101(5):e189–e191
Perez C, Gonzalez-Rincon J, Onaindia A et al, 2015, Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma. Haematologica 100(11):e450–e453
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 817
EP 818
DI 10.1007/s12253-018-0443-3
PG 2
ER
PT J
AU Ganesan, R
Sivalingam, N
AF Ganesan, Ramamoorthi
Sivalingam, Nageswaran
TI Transforming Growth Factor Beta 2 Inhibits Growth and Proliferation Potential of Smad4 and p53 Mutated Human Colon Adenocarcinoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Ganesan, Ramamoorthi] SRM Institute of Science and Technology, School of Bioengineering, Department of Biotechnology, 603203 Kattankulathur, Tamilnadu, India.
[Sivalingam, Nageswaran] SRM Institute of Science and Technology, School of Bioengineering, Department of Biotechnology, 603203 Kattankulathur, Tamilnadu, India.
RP Sivalingam, N (reprint author), SRM Institute of Science and Technology, School of Bioengineering, Department of Biotechnology, 603203 Kattankulathur, India.
EM nageswaran.s@ktr.srmuniv.ac.in
CR Siegel R, Ma J, Zou Z, Jemal A, 2014, Cancer statistics 2014. CA Cancer J Clin 64:9–29
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 819
EP 821
DI 10.1007/s12253-018-0423-7
PG 3
ER
PT J
AU Jo, SY
Kim, SS
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Soo Sung
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Candidate Tumor Suppressor Gene EAF2 is Mutated in Colorectal and Gastric Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Soo Sung] The Catholic University of Korea, College of Medicine, Department of Internal MedicineSeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Simone F, Luo RT, Polak PE, Kaberlein JJ, Thirman MJ, 2003, ELLassociated factor 2, EAF2), a functional homolog of EAF1 with alternative ELL binding properties. Blood 101:2355–2362
Xiao W, Zhang Q, Jiang F, Pins M, Kozlowski JM, Wang Z, 2003, Suppression of prostate tumor growth by U19, a novel testosterone-regulated apoptosis inducer. Cancer Res 63:4698– 4704
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Oh HR, An CH, Yoo NJ, Lee SH, 2015, Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in gastric and colorectal cancers. Pathol Oncol Res 21:713–718
Liu JX, Zhang D, Xie X, Ouyang G, Liu X, Sun Y, Xiao W, 2013, Eaf1 and Eaf2 negatively regulate canonical Wnt/β-catenin signaling. Development 140:1067–1078
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 823
EP 824
DI 10.1007/s12253-018-0461-1
PG 2
ER
PT J
AU Son, JH
Choi, JE
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Promoter Mutation Analysis of ALDOA Gene in Solid Tumors and Acute Leukemias
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Chang YC, Yang YC, Tien CP, Yang CJ, Hsiao M, 2018, Roles of aldolase family genes in human cancers and diseases. Trends Endocrinol Metab 29:549–559
Ji S, Zhang B, Liu J, Qin Y, Liang C, Shi S, Jin K, Liang D, Xu W, Xu H, Wang W, Wu C, Liu L, Liu C, Xu J, Ni Q, Yu X, 2016, ALDOAfunctions as an oncogene in the highlymetastatic pancreatic cancer. Cancer Lett 374:127–135
Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G, 2017, Recurrent and functional regulatory mutations in breast cancer. Nature 547:55–60
Heng J, Guo X, Wu W, Wang Y, Li G, Chen M, Peng L, Wang S, Dai L, Tang L, Wang J, 2017, Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients. PLoS One 12:e0174022
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2019
VL 25
IS 2
BP 825
EP 826
DI 10.1007/s12253-018-0530-5
PG 2
ER
PT J
AU Zhang, Xp
Cheng, Qh
Yang, Hj
Qiao, Eq
AF Zhang, Xi-ping
Cheng, Qi-hui
Yang, Hong-jian
Qiao, En-qi
TI Research Progresses in Cancer Stem Cells of Three Common Fertility-Related Female Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cancer stem cells; Female; Malignant tumors; Breast Cancer; Ovarian Cancer; Cervical Cancer
ID Cancer stem cells; Female; Malignant tumors; Breast Cancer; Ovarian Cancer; Cervical Cancer
AB With abilities to renew themselves and lead to heterogeneity of tumors, cancer stem cells (CSCs) are similar to stem cells. As three leading causes of death that endanger women’s health, breast cancer, ovarian cancer and cervical cancer are characterized by high degree of malignancy, metastasis and recurrence. Associated with women’s fertility, these three malignancies are common and representative among females. These years, research findings have suggested that CSCs are closely connected with many cancers (including aforementioned three malignancies) and several processes of tumors such as their genesis and development. CSCs have become great concerns for current cancer treatment and interventions. This paper does not only summarize roles of CSCs in genesis, development, drug resistance, metastasis and recurrence of breast cancer, ovarian cancer and cervical cancer, but also proposes potential methods of treatment and intervention, in hope of inspiring readers and researchers.
C1 [Zhang, Xi-ping] Zhejiang Cancer Hospital, Department of Breast Surgery, 310022 Hangzhou, Zhejiang Province, China.
[Cheng, Qi-hui] Hangzhou First People’s Hospital,, Department of Obstetrics and Gynecology, 310006, Hangzhou, Zhejiang Province, China.
[Yang, Hong-jian] Zhejiang Cancer Hospital, Department of Breast Surgery, 310022 Hangzhou, Zhejiang Province, China.
[Qiao, En-qi] Zhejiang Cancer Hospital, Department of Breast Surgery, 310022 Hangzhou, Zhejiang Province, China.
RP Zhang, Xp (reprint author), Zhejiang Cancer Hospital, Department of Breast Surgery, 310022 Hangzhou, China.
EM zxp99688@sina.com
CR Luo M, Clouthier SG, Deol Y, Liu S, Nagrath S, Azizi E,Wicha MS, 2015, Breast cancer stem cells: current advances and clinical implications. Methods Mol Biol 1293:1–49
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Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Endo Y, Hosoda M, Doihara H, Miyoshi S, Yamashita H, Collaborative Study Group of Scientific Research of the Japanese Breast Cancer S, 2016, Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence. Breast Cancer Res 18(1):73–84
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 827
EP 835
DI 10.1007/s12253-018-0448-y
PG 9
ER
PT J
AU Liu, C
Jin, J
Liang, D
Gao, Z
Zhang, Y
Guo, T
He, Y
AF Liu, Congmin
Jin, Jing
Liang, Di
Gao, Zhaoyu
Zhang, Yachen
Guo, Tiantian
He, Yutong
TI Long Noncoding RNA PVT1 as a Novel Predictor of Metastasis, Clinicopathological Characteristics and Prognosis in Human Cancers: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Long non-coding RNA; Plasmacytoma variant translocation 1; Metastasis; Clinical stage; Prognosis; Meta-analysis
ID Long non-coding RNA; Plasmacytoma variant translocation 1; Metastasis; Clinical stage; Prognosis; Meta-analysis
AB The present meta-analysis aimed to systematically evaluates the metastasis, clinical stage, and prognostic value regarding the expression levels of PVT1 in various cancers. Relevant literatures were searched in PubMed, Cochrane Library, Web of science, Embase databases, Chinese National Knowledge Infrastructure and Wanfang from inception up to 22 August 2017. After data were extracted, a meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. The meta-analysis showed that high expression of PVT1 could predict more lymph node metastasis (LNM) (Odds ratio, OR = 2.83, 95%confidence interval, CI: 1.76–4.54, P < 0.0001), distant metastasis (DM) (OR = 3.60, 95% CI: 1.08–12.03, P = 0.04), advanced clinical stage (OR = 4.37, 95% CI: 3.45–5.54, P < 0.00001) and poor overall survival (Hazard ratio, HR = 2.08, 95% CI: 1.82–2.37, P < 0.00001)in cancer. Subgroup analysis in different systems also showed the same results, including respiratory system, digestive system, urinary system and other systems, especially in respiratory system (LNM, OR = 4.57, 95% CI: 2.41–8.68, P < 0.00001; clinical stage, OR = 5.59, 95% CI: 3.59–8.71, P < 0.00001; OS, HR = 2.43, 95% CI: 1.98–2.99, P < 0.00001). These results suggest that PVT1 could serve as a novel biomarker for metastasis, clinical stage and poor prognosis in various tumors.
C1 [Liu, Congmin] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[Jin, Jing] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[Liang, Di] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[Gao, Zhaoyu] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[Zhang, Yachen] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[Guo, Tiantian] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
[He, Yutong] Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, Hebei, China.
RP He, Y (reprint author), Fourth Hospital of Hebei Medical University, Department of Medical Oncology, 050000 Shijiazhuang, China.
EM hytong69@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 837
EP 847
DI 10.1007/s12253-018-0451-3
PG 11
ER
PT J
AU Ren, HY
Shen, JX
Mao, XM
Zhang, XY
Zhou, P
Li, SY
Zheng, ZW
Shen, DY
Meng, JR
AF Ren, Hong-Yue
Shen, Jin-Xing
Mao, Xiao-Mei
Zhang, Xiao-Yun
Zhou, Pan
Li, Si-Yang
Zheng, Zhi-Wei
Shen, Dong-Yan
Meng, Jia-Rong
TI Correlation Between Tumor Vasculogenic Mimicry and Poor Prognosis of Human Digestive Cancer Patients: A Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Vasculogenic mimicry; digestive cancer; prognosis; meta-analysis
ID Vasculogenic mimicry; digestive cancer; prognosis; meta-analysis
AB Vasculogenic mimicry (VM) is a new pattern of blood supplement independent of endothelial vessels, which is related with tumor invasion, metastasis and prognosis. However, the role of VM in the prognosis of cancer patients is controversial. This study aimed to perform a meta-analysis of the published data to attempt to clarify the prognostic value of VM in the digestive cancer. Relevant studies were retrieved from the PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and VIP databases published before March 29, 2018. Studies were included if they detected VM in the digestive cancer and analyzed the overall survival (OS) or disease-free survival (DFS) according to VM status. Two independent reviewers screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was performed using STATA 12.0 software. A total of 22 studies with 2411 patients were included in this meta-analysis. Meta-analysis showed that VM was related with the poor OS (HR = 2.30, 95% CI: 2.06–2.56, P < 0.001) and DFS (HR = 2.60, 95% CI: 2.07–3.27, P < 0.001) of patients with digestive cancer. Subgroup analysis showed VM was related with tumor differentiation, lymph node metastasis and TNM stage. Moreover, the present meta-analysis was reliable, and there was no obvious publication bias. This meta-analysis suggested that VM was a poor prognosis of digestive cancer patients. Further large and well-designed studies are required.
C1 [Ren, Hong-Yue] The Affiliated Southeast Hospital of Xiamen University, Department of Pathology, 363000 Zhangzhou, Fujian Province, China.
[Shen, Jin-Xing] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Mao, Xiao-Mei] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Zhang, Xiao-Yun] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Zhou, Pan] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Li, Si-Yang] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Zheng, Zhi-Wei] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Shen, Dong-Yan] The First Affiliated Hospital of Xiamen University, Biobank, No 55 Zhenhai Road, 361003 Xiamen, Fujian Province, China.
[Meng, Jia-Rong] The Affiliated Southeast Hospital of Xiamen University, Department of Pathology, 363000 Zhangzhou, Fujian Province, China.
RP Meng, JR (reprint author), The Affiliated Southeast Hospital of Xiamen University, Department of Pathology, 363000 Zhangzhou, China.
EM mengjiarong175@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 849
EP 858
DI 10.1007/s12253-018-0496-3
PG 10
ER
PT J
AU Al-Rugeebah, A
Alanazi, M
Parine, RN
AF Al-Rugeebah, Arwa
Alanazi, Mohammed
Parine, Reddy Narasimha
TI MEG3: an Oncogenic Long Non-coding RNA in Different Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE MEG3; lncRNA; p53; Cancer; Methylation; Angiogenesis
ID MEG3; lncRNA; p53; Cancer; Methylation; Angiogenesis
AB Long noncoding RNAs (lncRNAs) have recently considered as central regulators in diverse biological processes and emerged as vital players controlling tumorigenesis. Several lncRNAs can be classified into oncogenes and tumor suppressor genes depending on their function in cancer. A maternally expressed gene 3 (MEG3) gene transcripts a 1.6 kb lncRNA whose act as an antitumor component in different cancer cells, such as breast, liver, glioma, colorectal, cervical, gastric, lung, ovarian and osteosarcoma cancer cells. The present review highlights biological function of MEG3 to repress tumor through regulating the major tumor suppressor genes p53 and Rb, inhibiting angiogenesis-related factor, or controlling miRNAs. On the other hand, previous studies have also suggested that MEG3 mediates epithelial-mesenchymal transition (EMT). However, deregulation of MEG3 is associated with the development and progression of cancer, suggesting that MEG3 may function as a potential biomarker and therapeutic target for human cancers.
C1 [Al-Rugeebah, Arwa] King Saud University, College of Science, Genome Research ChairRiyadh, Saudi Arabia.
[Alanazi, Mohammed] King Saud University, College of Science, Genome Research ChairRiyadh, Saudi Arabia.
[Parine, Reddy Narasimha] King Saud University, College of Science, Genome Research ChairRiyadh, Saudi Arabia.
RP Parine, RN (reprint author), King Saud University, College of Science, Genome Research Chair, Riyadh, Saudi Arabia.
EM reddyparine@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 859
EP 874
DI 10.1007/s12253-019-00614-3
PG 16
ER
PT J
AU Xu, N
Wang, L
Sun, P
Xu, S
Fu, Sh
Sun, Z
AF Xu, Ning
Wang, Lili
Sun, Ping
Xu, Suyang
Fu, Shiping
Sun, Zhihua
TI Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell Proliferation and Metastasis in Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ARID1A; Osteosarcoma; Tumour suppressor; Proliferation; Metastasis Prognosis
ID ARID1A; Osteosarcoma; Tumour suppressor; Proliferation; Metastasis Prognosis
AB AT-rich interactive domain-containing protein 1A (ARID1A) has been shown to function as a tumour suppressor in various malignancies. However, the biological role of ARID1A in osteosarcoma is not clear. The present study aimed to investigate the expression pattern, prognostic value and the biological role of ARID1A in human osteosarcoma. ARID1A expression in 53 osteosarcoma surgical specimens was examined by quantitative real-time polymerase chain reaction, and its clinical significance was analysed. The role of ARID1A in cell proliferation, apoptosis, and metastasis were examined. ARID1A mRNA expression were significantly down-regulated in osteosarcoma tumours from that in matched adjacent non-tumour tissues. ARID1A expression was significantly inversely correlated with tumour stage and distant metastasis, as well as poor overall survival in patients with osteosarcoma. Furthermore, ARID1A mRNA was downregulated in four human osteosarcoma cell lines MG-63, U2OS, HOS and Saos-2. Restoring of ARID1A expression in MG-63 and U2OS cells significantly inhibited cell proliferation and metastasis in vitro. Collectively, our data demonstrate that ARID1A may serve as a tumour suppressor in osteosarcoma progression, and represent a valuable prognostic marker and potential therapeutic target for osteosarcoma.
C1 [Xu, Ning] Shanghai Eighth People’s Hospital, Departments of Orthopedics, 200235 Shanghai, China.
[Wang, Lili] Bengbu Medical College, 233030 Bengbu, Anhui, China.
[Sun, Ping] Shanghai Eighth People’s Hospital, Departments of Orthopedics, 200235 Shanghai, China.
[Xu, Suyang] Shanghai Eighth People’s Hospital, Departments of Orthopedics, 200235 Shanghai, China.
[Fu, Shiping] Shanghai Eighth People’s Hospital, Departments of Orthopedics, 200235 Shanghai, China.
[Sun, Zhihua] Xiangyang Central Hospital, Departments of Oncology, No 136 Jingzhou street, 441021 Xiangyang, Hubei, China.
RP Sun, Z (reprint author), Xiangyang Central Hospital, Departments of Oncology, 441021 Xiangyang, China.
EM drzh_sun802@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 875
EP 881
DI 10.1007/s12253-017-0338-8
PG 7
ER
PT J
AU Peng, W
Wu, J
Fan, H
Lu, J
Feng, J
AF Peng, Wei
Wu, Jianzhong
Fan, Hong
Lu, Jianwei
Feng, Jifeng
TI LncRNA EGOT Promotes Tumorigenesis Via Hedgehog Pathway in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; EGOT; lncRNA; Tumorigenesis; Hedgehog
ID Gastric cancer; EGOT; lncRNA; Tumorigenesis; Hedgehog
AB Gastric cancer (GC) is one of the mostly terminal malignancies with poor prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the breast cancer. However, the function of EGOT in GC remains unknown. This work was to explore the clinical value and biological significance of EGOT in GC. EGOT levels in GC tissue and cell were analyzed by qRT–PCR. After knockdown of EGOT, GC cell growth and cycle progression were detected. The expression of EGOT was observably elevated in GC.Upregulation of EGOT was related with lymphatic metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could significantly inhibit GC cell proliferation and arrest cycle progression in G1 phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog signaling pathway in GC cells. EGOT functions as an oncogene in GC, and may be useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.
C1 [Peng, Wei] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, No. 42 Baiziting Road, 210009 Nanjing, China.
[Wu, Jianzhong] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Laboratory of Cancer Research, No. 42 Baiziting Road, 210009 Nanjing, China.
[Fan, Hong] First People’s Hospital of Yunnan Province, Department of Gastroenterology, No. 175 Jinbi Road, 650032 Kunming, China.
[Lu, Jianwei] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, No. 42 Baiziting Road, 210009 Nanjing, China.
[Feng, Jifeng] Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, No. 42 Baiziting Road, 210009 Nanjing, China.
RP Feng, J (reprint author), Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Department of Medical Oncology, 210009 Nanjing, China.
EM willgeek01@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 883
EP 887
DI 10.1007/s12253-017-0367-3
PG 5
ER
PT J
AU Xiao, GQ
Barrett, MM
Yang, Q
Unger, DP
AF Xiao, Guang-Qian
Barrett, M Mary
Yang, Qi
Unger, D Pamela
TI Clinicopathologic and Immunohistochemical Study of Combined Small Cell Carcinoma and Urothelial Carcinoma Molecular Subtype
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urothelial carcinoma; Small cell carcinoma of urinary bladder; Molecular subtype; Immunohistochemistry
ID Urothelial carcinoma; Small cell carcinoma of urinary bladder; Molecular subtype; Immunohistochemistry
AB Muscle invasive bladder cancer, an aggressive disease with heterogeneous molecular profiles, has recently been subclassified into three major molecular subtypes -basal, luminal and "p53-like" urothelial carcinomas (UCas), which bear prognostic and therapeutic implication. Similar to breast cancer, basal and luminal subtype UCas are designated by basal (CK5/14) and luminal (CK20) markers. The "p53-like" subtype presents with wild-type p53 gene with upregulated p53 pathways and is implicated in chemoresistance. Urinary bladder is one of the most common primary sites of extrapulmonary small cell carcinoma (SmCC). Bladder SmCC frequently coexists with UCa; however, the relation of SmCC with specific UCa molecular subtypes has not been studied. The aim of this study is to investigate the clinicopathology and immunophenotypes of the combined SmCC and UCa molecular subtypes. A total of 22 combined SmCC and UCa cases were studied for the clinicopathology and immunohistochemical (IHC) profiles by luminal and basal cell markers as well as Her2/Neu and p53. Our results demonstrated that all the urinary bladder SmCCs were associated with high grade UCas. They were more commonly seen in older male patients with a smoking history and had a poor prognosis. Based on the reported molecular subtyping, the UCas could be immunohistochemically subclassified into luminal, basal, dual and null types, which showed different clinicopathologic and IHC features. Compared to non-SmCC associated UCa, the subtypes of UCa in the combined SmCCs and UCas were characterized by: 1) Although overall luminal type was still relatively more common in men, basal marker-expressing subtypes were significantly increased in incidence and were more common in women. 2) Her2/Neu overexpression was more commonly observed in luminal than basal cell marker-expressing UCas. 3) IHC overexpression of p53 was common in all the subtypes, with UCas and SmCCs sharing the same p53 expression pattern. Although limited by relatively a small number of cases, the results of this study will enhance our understanding of the combined SmCC and UCa entity and potentially lead to a future therapeutic management.
C1 [Xiao, Guang-Qian] University of Southern California, Keck Medical Center, Department of Pathology, 1500 San Pablo Street, 90033 Los Angeles, CA, USA.
[Barrett, M Mary] University of Rochester Medical Center, Department of Pathology & Laboratory MedicineRochester, NY, USA.
[Yang, Qi] University of Rochester Medical Center, Department of Pathology & Laboratory MedicineRochester, NY, USA.
[Unger, D Pamela] Lenox Hill Hospital-Northwell Health System, Department of PathologyNew York, NY, USA.
RP Xiao, GQ (reprint author), University of Southern California, Keck Medical Center, Department of Pathology, 90033 Los Angeles, USA.
CR Falke J, Witjes JA, 2011, Contemporary management of low-risk bladder cancer. Nat Rev Urol 8(1):42–49
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Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J et al, 2014, Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25(2):152–165
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 889
EP 895
DI 10.1007/s12253-017-0369-1
PG 7
ER
PT J
AU Chen, J
Wang, H
Li, Z
AF Chen, Jun
Wang, Hong
Li, Zhiming
TI Association between Polymorphisms of X-Ray Repair Cross Complementing Group 1 Gene and Pancreatic Cancer Risk: a Systematic Review with Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE XRCC1; Polymorphisms; Pancreatic cancer; Meta-analysis
ID XRCC1; Polymorphisms; Pancreatic cancer; Meta-analysis
AB Emerging evidences have shown that common genetic polymorphisms in X-ray repair cross complementing group 1 (XRCC1) gene may be associated with the development of pancreatic cancer, but individually published studies and previous meta-analyses revealed inconclusive results. The aim of our study was to investigate the association between polymorphisms in XRCC1 gene and pancreatic cancer risk. We conducted a search of PubMed, Embase, the Cochrane Library and Web of Science databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined as measures of the strength of association between polymorphisms of XRCC1 and pancreatic cancer risk. Sensitivity analysis and publication bias were evaluated. All analyses were undertaken using the STATA 13.0. A total of 10 studies were included in this systematic review. Five common functional singlenucleotide polymorphisms (SNPs) in XRCC1 gene were found, including Arg399Gln G > A (rs25487), Arg194Trp C > T (rs1799782), Arg280His G > A (rs25489), c.1517G > C, c.1471G > A. Results from our stratified analysis based on Hardy-Weinberg equilibrium (HWE) showed that there was a robust significant association between Arg280His polymorphism and pancreatic cancer risk (allelic model, OR 0.743, 95% CI 0.576–0.958, P = 0.022; heterozygous model, OR 0.701, 95% CI 0.525–0.936, P = 0.016; dominant model, OR 0.710, 95% CI 0.537–0.939, P = 0.016). We also found a statistically significant association between c.1517G > C polymorphism and pancreatic cancer risk (Allelic model, OR 1.252, 95% CI 1.064–1.473, P = 0.007). No significant results were obtained for Arg399Gln, Arg194Trp and c.1471G > A polymorphisms. The present meta-analysis suggested that Arg280His and c.1517G > C polymorphisms in XRCC1 gene were associated with pancreatic cancer risk.
C1 [Chen, Jun] Xinjiang Medical University, Affiliated Hospital of Traditional Chinese Medicine, Department of General Surgery, No. 116 the Yellow River Road, 830000 Urumqi, China.
[Wang, Hong] Xinjiang Medical University, Affiliated Hospital of Traditional Chinese Medicine, Department of General Surgery, No. 116 the Yellow River Road, 830000 Urumqi, China.
[Li, Zhiming] Shihezi Hospital of Traditional Chinese Medicine, Department of SurgeryShihezi, China.
RP Chen, J (reprint author), Xinjiang Medical University, Affiliated Hospital of Traditional Chinese Medicine, Department of General Surgery, 830000 Urumqi, China.
EM chen_jun@hainan.net
CR Vaccaro V, Gelibter A, Bria E, Iapicca P, Cappello P, Di Modugno F et al, 2012, Molecular and genetic bases of pancreatic cancer. Curr Drug Targets 13(6):731–743
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Ginsberg G, Angle K, Guyton K, Sonawane B, 2011, Polymorphism in the DNA repair enzyme XRCC1: utility of current database and implications for human health risk assessment. Mutat Res Fundam Mol Mech Mutagen 727(1–2):1–15
Wood RD, Mitchell M, Sgouros J, Lindahl T, 2001, Human DNA repair genes. Science 291(5507):1284–1289
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Vidal AE, Boiteux S, Hickson ID, Radicella JP, 2001, XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J 20(22):6530–6539
Feng YZ, Liu YL, He XF, Wei W, Shen XL, Xie DL, 2014, Association between the XRCC1 Arg194Trp polymorphism and risk of cancer: evidence from 201 case-control studies. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine 35(11):10677–10697. , DOI 10.1007/s13277-014-2326-x
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Jiang H, Wu D, Ma D, Lin G, Liang J, Jin J, 2013, Association between X-ray repair cross-complementation group 1 rs25487 polymorphism and pancreatic cancer risk. Tumor Biol 34(6): 3417–3421
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Chen H, Tang C, Liu M, Zhou B, Kuang Y, Yuan T et al, 2013, Association of XRCC1 gene single nucleotide polymorphisms and susceptibility to pancreatic cancer in Chinese. Tumor Biol 35(1): 27–32. , DOI 10.1007/s13277-013-1001-y
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 897
EP 904
DI 10.1007/s12253-017-0364-6
PG 8
ER
PT J
AU Tsai, HL
Chen, YT
Yeh, YS
Huang, ChW
Ma, ChJ
Wang, JY
AF Tsai, Hsiang-Lin
Chen, Yi-Ting
Yeh, Yung-Sung
Huang, Ching-Wen
Ma, Cheng-Jen
Wang, Jaw-Yuan
TI Apical Lymph Nodes in the Distant Metastases and Prognosis of Patients with Stage III Colorectal Cancer with Adequate Lymph Node Retrieval Following FOLFOX Adjuvant Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Apical lymph nodes; Distant metastases; Prognosis; Stage III colorectal cancer
ID Apical lymph nodes; Distant metastases; Prognosis; Stage III colorectal cancer
AB The aim of the study was to assess apical lymph nodes (APNs) for predicting distant metastases in patients with stage III colorectal cancer (CRC) curatively treated with FOLFOX adjuvant chemotherapy and adequate lymph node retrieval. We investigated the correlation between APN metastasis and clinical outcomes. This retrospective study examined 97 patients. All patients were followed until death, loss to follow-up, or May 2017. Clinicopathological variables, including the APN status, were assessed. Multivariate logistic regression model was used to identify the independent risk factors for APN and distant metastases, and Cox proportional regression model was used to evaluate the association between APN metastasis and oncologic outcomes. Multivariate analyses revealed the N2 stage as an independent predictor of APN metastasis [P = 0.036; odds ratio (OR): 3.016; 95% confidence interval (CI): 1.076– 8.499], while APN metastasis was an independent risk factor for distant metastases (P < 0.001; OR: 13.876; 95% CI: 3.815–50.475). Furthermore, APN metastasis was an independent risk factor for poorer disease-free survival (DFS) and overall survival (OS) (P < 0.001 and P = 0.005, respectively). The liver (31.6%) was the most common site of distant metastases in patients with APN metastases. APN metastasis is an important prognostic factor for node-positive CRC; it enhanced the distant metastases in patients with stage III CRC curatively treated with adequate lymph node retrieval following FOLFOX adjuvant chemotherapy. Therefore, for patients with stage III CRC involving APN metastasis, prospectively randomized trials are mandatory to investigate different therapeutic strategies in addition to conventional FOLFOX adjuvant chemotherapy.
C1 [Tsai, Hsiang-Lin] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Chen, Yi-Ting] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
[Yeh, Yung-Sung] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Huang, Ching-Wen] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Ma, Cheng-Jen] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
[Wang, Jaw-Yuan] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100, Tzyou 1st Road, 807 Kaohsiung, Taiwan, Republic of China.
RP Wang, JY (reprint author), Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, 807 Kaohsiung, Taiwan, Republic of China.
EM cy614112@ms14.hinet.net;jayuwa@cc.kmu.edu.tw
CR Kawada H, Kurita N, Nakamura F, Kawamura J, Hasegawa S, Kotake K, Sugihara K, Fukuhara S, Sakai Y, 2014, Incorporation of apical lymph status into the seventh edition of the TNM classification improves prediction of prognosis in stage III colorectal cancer. Br J Surg 101:1143–1152
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Kang J, Hur H, Min BS, Kim NK, Lee KY, 2011, Prognostic impact of inferior mesenteric artery lymph node metastasis in colorectal cancer. Ann Surg Oncol 18:704–710
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Kobayashi H, Ueno H, Hashiguchi Y, Mochizuki H, 2006, Distribution of lymph node metastasis is a prognostic index in patients with stage III colon cancer. Surgery 139:516–522
Gundara JS, Gill AJ, Hugh TJ, Samra JS, 2013, Redefining the apical lymph node at right hemicolectomy. Eur J Surg Oncol 39: 662–665
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Ang CW, Tweedle M, Campbell F, 2011, Apical node metastasis independently predicts poor survival in Dukes’ C colorectal cancer. Color Dis 13:526–531
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Chen H, Wang Y, Liu H, Hu Y, Zhao L, Li G, Chi P, 2015, Factors influencing apical node metastasis in colorectal cancer patients treated with laparoscopic radical resection with D3 lymphadenectomy: results from two centers in China. Surg Today 45:569–575
Vaccaro CA, Bonadeo FA, BenatiML, QuintanaGM, Rubinstein F, Mullen E, Telenta M, Lastiri JM, 2004, Colorectal cancer staging: reappraisal of N/PN classification. Dis Colon Rectum 47:66–69
Kim JC, Lee KH, CS Y, Kim HC, Kim JR, Chang HM, Kim JH, Kim JS, Kim TW, 2004, The clinicopathological significance of inferior mesenteric lymph node metastasis in colorectal cancer. Eur J Surg Oncol 30:271–279
Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart A, 2010, Revised tumor and node categorization for rectal cancer based on surveillance, epidemiology, and end results and rectal pooled analysis outcomes. J Clin Oncol 28:256–263
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Yi JW, Lee TG, Lee HS, Heo SC, Jeong SY, Park KJ, Kang SB, 2012, Apical-node metastasis in sigmoid colon or rectal cancer: is it a factor that indicates a poor prognosis after high ligation? Int J Color Dis 27:81–87
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Duben J, Dudesek B, Hnatek L, Vazan P, Bakala J, Gatek J, 2010, Lymphatic mapping and biopsy of sentinel lymph nodes using combined methodology of in vivo application of patent blue and radionuclide and ex vivo detection of metastatic affection of lymph nodes in colorectal carcinoma. Rozhl Chir 89:695–701
ShiozawaM, AkikeM, Yamada R, Godai T, Yamamoto N, Saito H, Sugimasa Y, Takemiya S, Rino Y, Imada T, 2007, Clinicopathological features of skip metastasis in colorectal cancer. Hepato-Gastroenterology 54:81–84
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 905
EP 913
DI 10.1007/s12253-017-0381-5
PG 9
ER
PT J
AU Bartak, KB
Kalmar, A
Galamb, O
Wichmann, B
Nagy, BZs
Tulassay, Zs
Dank, M
Igaz, P
Molnar, B
AF Bartak, Kinga Barbara
Kalmar, Alexandra
Galamb, Orsolya
Wichmann, Barnabas
Nagy, Brigitta Zsofia
Tulassay, Zsolt
Dank, Magdolna
Igaz, Peter
Molnar, Bela
TI Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of Liquid Biopsy Analysis for Colorectal Cancer Detection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liquid biopsy; Plasma; cfDNA isolation; Blood collection; Colorectal cancer; DNA methylation
ID Liquid biopsy; Plasma; cfDNA isolation; Blood collection; Colorectal cancer; DNA methylation
AB During colorectal cancer (CRC) development tumor-derived cell-free DNA (cfDNA) can be released into the bloodstream. Many different cfDNA isolation methods and specific blood collection tubes preventing the release of genomic DNA and stabilizing cfDNA with preservative reagents became available. These factors may affect greatly on the further liquid biopsy analyses. Our aim was to test different blood collection tubes and cfDNA isolation methods to determine whether these factors influence the cfDNA amount and the promoter methylation of four previously described hypermethylated biomarkers. Three manual isolation methods (High Pure Viral Nucleic Acid Large Volume Kit; Epi proColon 2.0 Kit; Quick-cfDNA™ Serum & Plasma Kit) and automated sample preparation systems (InviGenius and InviGenius PLUS) were examined. Furthermore, K3EDTA Vacuette tubes and Streck Cell-Free DNA BCT® tubes were compared. After cfDNA isolation and bisulfite conversion of samples, the methylation level of SFRP1, SFRP2, SDC2, and PRIMA1 were defined with MethyLight assays.We have ascertained that there are differences between the cfDNA amounts depending on the isolation methods. Higher cfDNA yield was observed using InviGenius system than column-based manual isolation method; however, InviGenius PLUS has produced lower cfDNA amounts. No remarkable variance could be found between K3EDTA and Streck tubes; slightly higher cfDNA quantity was detected in 60% of plasma samples using Streck tubes. In point of methylation level and frequency, manual column-based isolation produced more consistent results. Automated cfDNA extraction systems are easy-to-use and high-throughput; however, further improvements in the isolation protocols might lead to the increase of the sensitivity of further methylation analysis.
C1 [Bartak, Kinga Barbara] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, H-1088 Budapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, H-1088 Budapest, Hungary.
[Galamb, Orsolya] Hungarian Academy of Sciences, Molecular Medicine Research Group, H-1088 Budapest, Hungary.
[Wichmann, Barnabas] Hungarian Academy of Sciences, Molecular Medicine Research Group, H-1088 Budapest, Hungary.
[Nagy, Brigitta Zsofia] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, H-1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, H-1088 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of Oncology, H-1083 Budapest, Hungary.
[Igaz, Peter] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi str. 46, H-1088 Budapest, Hungary.
[Molnar, Bela] Hungarian Academy of Sciences, Molecular Medicine Research Group, H-1088 Budapest, Hungary.
RP Bartak, KB (reprint author), Semmelweis University, 2nd Department of Internal Medicine, H-1088 Budapest, Hungary.
EM bartak.barbara.kinga@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 915
EP 923
DI 10.1007/s12253-018-0382-z
PG 9
ER
PT J
AU Kumari, S
Husain, N
Agarwal, A
Neyaz, A
Gupta, S
Chaturvedi, A
Lohani, M
Sonkar, AA
AF Kumari, Swati
Husain, Nuzhat
Agarwal, Akash
Neyaz, Azfar
Gupta, Sameer
Chaturvedi, Arun
Lohani, Mohtashim
Sonkar, Arun Abhinav
TI Diagnostic Value of Circulating Free DNA Integrity and Global Methylation Status in Gall Bladder Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gall bladder carcinoma (GBC); Circulating free DNA (cfDNA); cfDNA integrity; Global DNA methylation; Liquid biopsy
ID Gall bladder carcinoma (GBC); Circulating free DNA (cfDNA); cfDNA integrity; Global DNA methylation; Liquid biopsy
AB The current study investigates the role of circulating free DNA (cfDNA) as a liquid biopsy in diagnosis gall bladder carcinoma (GBC) utilizing levels of long DNA fragments (ALU247) derived from tumor necrosis, short apoptotic fragments (ALU115) denoting total cfDNA and cfDNA integrity denoting ratio of ALU247 and ALU115. The global methylation status of cfDNA was also estimated with the hypothesis that these parameters provide a diagnostic distinction between cancer and non-cancer subjects, with higher or altered values favoring presence of malignancy. Study group included 60 cases of GBC and 36 controls including diseased controls (cholecystitis) and healthy subjects. Median levels of ALU115, ALU247 and cfDNA integrity were significantly different in GBC at 1790.88, 673.75, 0.4718 vs. controls at 840.73, 165.03, 0.1989 ng/ml respectively. Global DNA methylation was not significantly different between GBC at 0.679% and controls at 0.695%. The sensitivity and specificity of ALU 247 in discriminating GBC from controls was highest with a sensitivity, specificity and diagnostic accuracy of 80.0%, 86.1% and 82.2% respectively. Global DNA methylation showed lowest sensitivity of 55.0% and specificity of 50.0%. Clinicopathological parameters showing significant association with cfDNA integrity, on ROC curve analysis, showed significant diagnostic discrimination of the tumor stage, lymphovascular invasion, disease stage and grade histology. This is a first time analysis of ALU115, ALU247 and cfDNA integrity in the diagnosis of GBC and confirms that the combination of ALU247 and cfDNA integrity provides good sensitivity, specificity and diagnostic accuracy in discriminating GBC from controls as well correlates with aggressive disease parameters.
C1 [Kumari, Swati] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, U.P., India.
[Husain, Nuzhat] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, U.P., India.
[Agarwal, Akash] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Surgical Oncology, 226010 Lucknow, U.P., India.
[Neyaz, Azfar] Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, U.P., India.
[Gupta, Sameer] King George’s Medical University, Department of Surgical Oncology, 226003 Lucknow, U.P., India.
[Chaturvedi, Arun] King George’s Medical University, Department of Surgical Oncology, 226003 Lucknow, U.P., India.
[Lohani, Mohtashim] Integral University, Department of Biosciences, 226026 Lucknow, U.P., India.
[Sonkar, Arun Abhinav] King George’s Medical University, Department of Surgery, 226003 Lucknow, U.P., India.
RP Husain, N (reprint author), Dr. Ram Manohar Lohia Institute of Medical Sciences, Department of Pathology, 226010 Lucknow, India.
EM drnuzhathusain@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 925
EP 936
DI 10.1007/s12253-017-0380-6
PG 12
ER
PT J
AU Wang, M
An, Sh
Wang, D
Ji, H
Geng, M
Guo, X
Wang, Z
AF Wang, Ming
An, Shuhong
Wang, Diyi
Ji, Haizhen
Geng, Min
Guo, Xingjing
Wang, Zhaojin
TI Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Proteomic; Protease-activated receptors-4; Apoptosis; Tumor suppressor; Esophageal squamous cell carcinoma
ID Proteomic; Protease-activated receptors-4; Apoptosis; Tumor suppressor; Esophageal squamous cell carcinoma
AB Exposure to carcinogens of tobacco smoke may result in methylation of protease-activated receptors-4 (PAR4) gene and further induces the loss of PAR4 expression, which is considered to be involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC). Here we employed a TMT-based quantitative proteomic approach to identify PAR4-regulated changes of proteomic profiles in ESCC cells and to identify potentially therapeutic value. A total of 33 proteins were found significantly changed with 15 up-regulated and 18 down-regulated in PAR4-activating peptide (PAR4-AP) treated ESCC cells compared with controls. Bioinformatics analysis showed that key higher expressed proteins included those associated with apoptosis and tumor suppressor (e.g. CASP9), and lower expressed proteins included those associated with anti-apoptosis, autophagy and promoting cell proliferation (e.g. CHMP1B, PURA, PARG and HIST1H2AH).Western blot verified changes in five representative proteins including CASP9, CHMP1B, PURA, PARG and HIST1H2AH. Immunohistochemistry analysis showed that CHMP1B, PURA, PARG and HIST1H2AH expression in ESCC tissues were significantly higher than those in adjacent nontumorous tissues. Our findings will be helpful in further investigations into the functions and molecular mechanisms of PAR4 in ESCC.
C1 [Wang, Ming] Taishan Medical University, Department of Human Anatomy, 2 Ying Sheng Dong Lu, 271000 Taian, China.
[An, Shuhong] Taishan Medical University, Department of Human Anatomy, 2 Ying Sheng Dong Lu, 271000 Taian, China.
[Wang, Diyi] Affiliated Hospital of Taishan Medical University, Department of Pathology, 271000 Taian, China.
[Ji, Haizhen] Taishan Medical University, Department of Physiology, 271000 Taian, China.
[Geng, Min] Taishan Medical University, Department of Human Anatomy, 2 Ying Sheng Dong Lu, 271000 Taian, China.
[Guo, Xingjing] Taishan Medical University, Department of Physiology, 271000 Taian, China.
[Wang, Zhaojin] Taishan Medical University, Department of Human Anatomy, 2 Ying Sheng Dong Lu, 271000 Taian, China.
RP Wang, Z (reprint author), Taishan Medical University, Department of Human Anatomy, 271000 Taian, China.
EM zjwang@tsmc.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 937
EP 943
DI 10.1007/s12253-018-0395-7
PG 7
ER
PT J
AU Semushina, GS
Aronov, AD
Moiseeva, VE
AF Semushina, G Svetlana
Aronov, A Dmitry
Moiseeva, V Ekaterina
TI Local Interleukin-2 Immunotherapy of Breast Cancer: Benefit and Risk in a Spontaneous Mouse Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Interleukin-2; 3S–paradigm; Spontaneous mouse model; BLRB
ID Breast cancer; Interleukin-2; 3S–paradigm; Spontaneous mouse model; BLRB
AB Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pathological characteristics of the familial set of human breast cancer. Then we advanced a novel 3S–paradigm of anticancer research that helped to develop selection criteria and to estimate benefit/risk of local interleukin-2 (IL-2) effects in this spontaneous mouse model. In this paper, the efficacy of single and triple local IL-2 doses is compared using properly selected murine BLRB females based on our previously published data. Only BLRB females bearing spontaneous mammary tumors without subclinical period were used. The tumor growth rate and recipient survival of single and triple IL-2 applications were compared with corresponding parameter values of untreated control. Tumor growth rate was decreased in both experimental groups versus control parameter values. Single IL-2 application resulted in a significant prolongation of the average survival time while triple application caused acute tumor rejection in some females decreasing the survival time of the rest of the recipients. As a result, proper treatment protocol in accurately selected females allowed increasing the complete response rate to 14% in spontaneous mouse model of breast cancer. In conclusion, our approaches may demonstrate the principle methodology developing preselection procedure for breast cancer patients for local IL-2 therapy application.
C1 [Semushina, G Svetlana] Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str., 16/10, GSP-7, 117997 Moscow, Russian Federation.
[Aronov, A Dmitry] Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str., 16/10, GSP-7, 117997 Moscow, Russian Federation.
[Moiseeva, V Ekaterina] Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str., 16/10, GSP-7, 117997 Moscow, Russian Federation.
RP Moiseeva, VE (reprint author), Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russian Federation.
EM evmoise@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 945
EP 951
DI 10.1007/s12253-018-0396-6
PG 7
ER
PT J
AU Mo, JS
Park, YR
Chae, SCh
AF Mo, Ji-Su
Park, Young-Ran
Chae, Soo-Cheon
TI MicroRNA 196B Regulates HOXA5, HOXB6 and GLTP Expression Levels in Colorectal Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA; MIR196B; HOXA5; GLTP; Colorectal cancer
ID MicroRNA; MIR196B; HOXA5; GLTP; Colorectal cancer
AB MiRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. Previously we identified colorectal cancer (CRC) associated MIR196B, which was specifically up-regulated in CRC cells and tissue. We also identified 18 putative MIR196B target genes by comparing the mRNAs down-regulated in MIR196B-overexpressed cells with MIR196B target genes predicted by public bioinformatics tools. In this study, we verified the association between MIR196B and three genes, HOXA5, HOXB6 and GLTP. HOXA5, HOXB6 and GLTP transcripts were directly down-regulated by MIR196B. The mRNA and proteins levels of HOXA5, HOXB6 and GLTP were also down-regulated in CRC cells by the up-regulated MIR196B. GLTP protein expression was decreased in CRC tissues compared to adjacent non-tumor tissues. These results suggest that HOXA5, HOXB6, and GLTP were direct target genes of MIR196B in CRC cells, and that the up-regulated MIR196B in CRC tissue regulates the expression levels of HOXA5, HOXB6, and GLTP during colorectal carcinogenesis.
C1 [Mo, Ji-Su] Wonkwang University, School of Medicine, Department of Pathology, 54538 Iksan, Chonbuk, South Korea.
[Park, Young-Ran] Wonkwang University, School of Medicine, Department of Pathology, 54538 Iksan, Chonbuk, South Korea.
[Chae, Soo-Cheon] Wonkwang University, School of Medicine, Department of Pathology, 54538 Iksan, Chonbuk, South Korea.
RP Chae, SCh (reprint author), Wonkwang University, School of Medicine, Department of Pathology, 54538 Iksan, South Korea.
EM chaesc@wku.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 953
EP 959
DI 10.1007/s12253-018-0399-3
PG 7
ER
PT J
AU Azevedo, PA
Silva, NS
Reichert, A
Lima, F
Junior, E
Rueff, J
AF Azevedo, P Ana
Silva, N Susana
Reichert, Alice
Lima, Fernando
Junior, Esmeraldina
Rueff, Jose
TI The Role of Caspase Genes Polymorphisms in Genetic Susceptibility to Philadelphia-Negative Myeloproliferative Neoplasms in a Portuguese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Philadelphia-negative myeloproliferative neoplasms; Genetic susceptibility; Caspase genes polymorphisms; Janus kinase 2
ID Philadelphia-negative myeloproliferative neoplasms; Genetic susceptibility; Caspase genes polymorphisms; Janus kinase 2
AB Our main aim was to evaluate the role of caspases’ genes SNPs in Philadelphia-chromosome negative chronic myeloproliferative neoplasms (PN-MPNs) susceptibility. A case-control study in 133 Caucasian Portuguese PN-MPNs patients and 281 matched controls was carried out, studying SNPs in apoptosis related caspases: rs1045485 and rs1035142 (CASP8), rs1052576, rs2308950, rs1132312 and rs1052571 (CASP9), rs2227309 and rs2227310 (CASP7) and rs13006529 (CASP10). After stratification by pathology diagnosis for essential thrombocythemia (ET), female gender or JAK2 positive, there is a significant increased risk for those carrying at least one variant allele for CASP9 (C653T) polymorphism (OR 2.300 CI 95% [1.180– 4.484], P = 0.014). However, when considered individually, none of the studied caspases polymorphisms was associated with PN-MPNs risk. Our results do not reveal a significant involvement of caspase genes polymorphisms on the individual susceptibility towards PN-MPNs as a whole. However, for essential thrombocythemia (ET), female gender or JAK2 positive, there is a significant increased risk to those carrying at least one variant allele for CASP9. Although larger studies are required to confirm these results and to provide conclusive evidence of association between these and other caspases variants and PN-MPNs susceptibility, these new data may contribute to a best knowledge of the pathophysiology of these disorders and, in the future, to a more rational and efficient choice of therapeutic strategies to be adopted in PN-MPNs treatment.
C1 [Azevedo, P Ana] Nova Medical School / Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Centre for Toxicogenomics and Human Health (ToxOmics), Campo dos Martires da Patria, 130, 1169-056 Lisbon, Portugal.
[Silva, N Susana] Nova Medical School / Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Centre for Toxicogenomics and Human Health (ToxOmics), Campo dos Martires da Patria, 130, 1169-056 Lisbon, Portugal.
[Reichert, Alice] Centro Hospitalar de Lisboa Ocidental (CHLO), Hospital de S. Francisco Xavier, Department of Clinical Haematology, Estrada Forte do Alto do Duque, 1449-005 Lisbon, Portugal.
[Lima, Fernando] Centro Hospitalar de Lisboa Ocidental (CHLO), Hospital de S. Francisco Xavier, Department of Clinical Haematology, Estrada Forte do Alto do Duque, 1449-005 Lisbon, Portugal.
[Junior, Esmeraldina] Centro Hospitalar de Lisboa Ocidental (CHLO), Hospital de S. Francisco Xavier, Department of Clinical Pathology, Estrada Forte do Alto do Duque, 1449-005 Lisbon, Portugal.
[Rueff, Jose] Nova Medical School / Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Centre for Toxicogenomics and Human Health (ToxOmics), Campo dos Martires da Patria, 130, 1169-056 Lisbon, Portugal.
RP Silva, NS (reprint author), Nova Medical School / Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Centre for Toxicogenomics and Human Health (ToxOmics), 1169-056 Lisbon, Portugal.
EM snsilva@nms.unl.pt;jose.rueff@nms.unl.pt
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 961
EP 969
DI 10.1007/s12253-018-0411-y
PG 9
ER
PT J
AU Urbanovska, I
Megova, HM
Dwight, Z
Kalita, O
Uvirova, M
Simova, J
Tuckova, L
Buzrla, P
Palecek, T
Hajduch, M
Dvorackova, J
Drabek, J
AF Urbanovska, Irena
Megova, Houdova Magdalena
Dwight, Zachary
Kalita, Ondrej
Uvirova, Magdalena
Simova, Jarmila
Tuckova, Lucie
Buzrla, Petr
Palecek, Tomas
Hajduch, Marian
Dvorackova, Jana
Drabek, Jiri
TI IDH Mutation Analysis in Glioma Patients by CADMA Compared with SNaPshot Assay and two Immunohistochemical Methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IDH1; IDH2; CADMA; Glioma; Mutation testing
ID IDH1; IDH2; CADMA; Glioma; Mutation testing
AB Mutations in IDH1/2 genes are a marker of good prognosis for glioma patients, associated with low grade gliomas and secondary glioblastomas. Immunohistochemistry and Sanger sequencing are current standards for IDH1/2 genotyping while many other methods exist. The aim of this study was to validate Competitive amplification of differentially melting amplicons (CADMA) PCR for IDH genotyping by comparison with SNaPshot assay and two immunohistochemical methods. In our study, 87 glioma patients (46 from Olomouc and 41 from Ostrava) were analyzed. IDH1/2 mutations in native bioptical samples were analyzed at DNA level by CADMA and SNaPshot while IDH1 mutations in FFPE samples were analyzed at protein level by two IHC methods. CADMA PCR sensitivity for IDH1 was 96.4% and specificity 100% for 86 concluded samples. SNaPshot assay sensitivity was 92.9% and specificity of 100% for 85 concluded samples. IHC in the laboratory no. 2 reached sensitivity 85.7% and specificity 100% for 86 concluded samples. IHC in the laboratory no. 4 reached sensitivity of 96.4% and specificity of 79.7% in 74 concluded samples. Only one IDH2 mutation was found by SNaPshot while CADMA yielded false negative result. In conclusion, CADMA is a valid method for IDH1 p.(R132H) testing with higher sensitivity than SNaPshot assay. Also, molecular genetic methods of IDH1 testing from native samples were more robust than IHC from FFPE.
C1 [Urbanovska, Irena] CGB Laboratory Inc.Ostrava, Czech Republic.
[Megova, Houdova Magdalena] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Hnevotinska 5, 779 00 Olomouc, Czech Republic.
[Dwight, Zachary] University of Utah, Department of PathologySalt Lake City, UT, USA.
[Kalita, Ondrej] University Hospital Olomouc, Department of NeurosurgeryOlomouc, Czech Republic.
[Uvirova, Magdalena] CGB Laboratory Inc.Ostrava, Czech Republic.
[Simova, Jarmila] CGB Laboratory Inc.Ostrava, Czech Republic.
[Tuckova, Lucie] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Department of Clinical and Molecular PathologyOlomouc, Czech Republic.
[Buzrla, Petr] University of Ostrava, Faculty of Medicine and University Hospital, Institute of Pathology, Syllabova 19, 703 00 Ostrava, Czech Republic.
[Palecek, Tomas] University Hospital Ostrava, Neurosurgery ClinicOstrava, Czech Republic.
[Hajduch, Marian] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Hnevotinska 5, 779 00 Olomouc, Czech Republic.
[Dvorackova, Jana] University of Ostrava, Faculty of Medicine, Department of Biomedical SciencesOstrava, Czech Republic.
[Drabek, Jiri] Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Hnevotinska 5, 779 00 Olomouc, Czech Republic.
RP Drabek, J (reprint author), Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, 779 00 Olomouc, Czech Republic.
EM jiri_drabek@seznam.cz
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 971
EP 978
DI 10.1007/s12253-018-0413-9
PG 8
ER
PT J
AU Leyh-Bannurah, SR
Trudel, D
Latour, M
Zaffuto, E
Grosset, AA
Tam, Ch
Ouellet, V
Graefen, M
Budaus, L
Aprikian, GA
Lacombe, L
Fleshner, EN
Gleave, EM
Mes-Masson, AM
Saad, F
Karakiewicz, IP
AF Leyh-Bannurah, Sami-Ramzi
Trudel, Dominique
Latour, Mathieu
Zaffuto, Emanuele
Grosset, Andree-Anne
Tam, Christine
Ouellet, Veronique
Graefen, Markus
Budaus, Lars
Aprikian, G Armen
Lacombe, Louis
Fleshner, E Neil
Gleave, E Martin
Mes-Masson, Anne-Marie
Saad, Fred
Karakiewicz, I Pierre
TI A Multi-Institutional Validation of Gleason Score Derived from Tissue Microarray Cores
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radical prostatectomy; Prostate cancer; Gleason grade agreement; Biochemical recurrence; Validation
ID Radical prostatectomy; Prostate cancer; Gleason grade agreement; Biochemical recurrence; Validation
AB To test the agreement between high-grade PCa at RP and TMA, and the ability of TMA to predict BCR. Validation of concordance between tissue microarray (TMA) and radical prostatectomy (RP) high-grade prostate cancer (PCa) is crucial because latter determines the treated natural history of PCa. We hypothesized that TMA Gleason score is in agreement with RP pathology and capable of accurately predicting biochemical recurrence (BCR). Data were provided from a multi-institutional Canadian sample of 1333 TMA and RP specimens with complete clinicopathological data. First, rate of agreement between TMA and high-grade Gleason at RP or biopsy and RP was tested. Second, ability of RP, TMA and biopsy to predict BCR was compared. Multivariable (MVA) Cox regression models were fitted and BCR rates were illustrated with Kaplan-Meier plots. Agreement between RP and TMA and between RP and biopsy was 72.6% (95% CI:69.7–75.5) and 60.4% (95% CI:57.2–63.6), respectively. In MVA predicting BCR, the accuracy for RP, TMA and biopsy was 0.73, 0.72 and 0.68, respectively. TMA added discriminatory ability among exclusively low-grade Gleason RP patients (p = 0.02), but did not improve BCR discrimination in exclusive high-grade PCa RP patients (p = 0.8). TMA Gleason grade accurately reflects presence of high-grade Gleason in RP specimen, accurately predicts BCR rates after RP and improves prediction of BCR in low-grade Gleason patients at RP.
C1 [Leyh-Bannurah, Sami-Ramzi] University of Montreal Health Center, Cancer Prognostics and Health Outcomes UnitMontreal, Canada.
[Trudel, Dominique] Universite de Montreal, Department of Pathology and Cellular BiologyMontreal, Canada.
[Latour, Mathieu] Universite de Montreal, Department of Pathology and Cellular BiologyMontreal, Canada.
[Zaffuto, Emanuele] University of Montreal Health Center, Cancer Prognostics and Health Outcomes UnitMontreal, Canada.
[Grosset, Andree-Anne] l’Universite de Montreal, Institut du Cancer de Montreal and Centre de recherche du centre hospitalierMontreal, QC, Canada.
[Tam, Christine] l’Universite de Montreal, Institut du Cancer de Montreal and Centre de recherche du centre hospitalierMontreal, QC, Canada.
[Ouellet, Veronique] l’Universite de Montreal, Institut du Cancer de Montreal and Centre de recherche du centre hospitalierMontreal, QC, Canada.
[Graefen, Markus] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Budaus, Lars] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Aprikian, G Armen] McGill University, Research Institute of McGill University Health Center and Department of Surgery (Urology)Montreal, QC, Canada.
[Lacombe, Louis] CHU de QuebecQuebec, Quebec, Canada.
[Fleshner, E Neil] University of Toronto, University Health Network, Department of SurgeryToronto, ON, Canada.
[Gleave, E Martin] University of British Columbia, Vancouver Prostate Centre & Department of Urologic ScienceVancouver, BC, Canada.
[Mes-Masson, Anne-Marie] Universite de Montreal, Department of MedecineMontreal, Canada.
[Saad, Fred] Universite de Montreal, Department of SurgeryMontreal, Canada.
[Karakiewicz, I Pierre] University of Montreal Health Center, Cancer Prognostics and Health Outcomes UnitMontreal, Canada.
RP Leyh-Bannurah, SR (reprint author), University of Montreal Health Center, Cancer Prognostics and Health Outcomes Unit, Montreal, Canada.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 979
EP 986
DI 10.1007/s12253-018-0408-6
PG 8
ER
PT J
AU Yonekura, S
Terauchi, F
Hoshi, K
Yamaguchi, T
Kawai, Sh
AF Yonekura, Satoru
Terauchi, Fumihito
Hoshi, Kenji
Yamaguchi, Takehiko
Kawai, Shigeo
TI Androgen Receptor Predicts First and Multiple Recurrences in Non-Muscle Invasive Urothelial Carcinoma of the Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Androgen receptor; Recurrence; Bladder cancer; Immunohistochemistry
ID Androgen receptor; Recurrence; Bladder cancer; Immunohistochemistry
AB The aim of this study is to investigate the role of androgen receptor (AR) expression on clinicopathologic characteristics, first recurrence free survival (RFS), progression free survival (PFS) and multiple recurrences in non-muscle invasive bladder cancer (NMIBC). AR expression in 40 paraffin-embedded specimens of primarily diagnosed NMIBC after transurethral resection was examined by immunohistochemistry using a monoclonal AR antibody. Associations between AR expression and clinicopathologic features and prognosis were statistically assessed. Multivariate Cox proportional hazards model was applied for evaluating predictive factors on RFS and PFS. For multiple recurrences, we used the Andersen-Gill model. AR was positive in 20/40 (50%) cases. Twenty-three patients (57.5%) had no recurrence, 10 (25.0%) had one recurrence, and 7 (17.5%) experiencedmore than one recurrence. AR expression and clinicopathologic features were not significantly correlated (P >0.05). Univariate analyses showed that AR expression was significantly associated with RFS and PFS (P <0.05). Via multivariate analyses, positive AR expression was significantly associated with lower risk of first recurrence (hazard ratio (HR) = 0.265; 95% confidence interval (95% CI) = 0.084–0.829; P = 0.022).Multivariate analysis of PFS was not feasible in our cohort.Using the multivariate Andersen-Gillmodel, positive AR expression in the primary tumor was an independent factor predicting lower risk ofmultiple recurrences (HR = 0.387, 95% CI = 0.161–0.927, P = 0.033). Androgen receptor expression is associated with first and multiple recurrences in NMIBC.
C1 [Yonekura, Satoru] Tochigi Medical Center Shimotsuga Hospital, Department of Pathology, 420-1 Ohira-machi Kawatsure, 329-4498 Tochigi, Tochigi, Japan.
[Terauchi, Fumihito] Tochigi Medical Center Shimotsuga Hospital, Department of Urology, 420-1 Ohira-machi Kawatsure, 329-4498 Tochigi, Tochigi, Japan.
[Hoshi, Kenji] Tochigi Medical Center Shimotsuga Hospital, Department of Pathology, 420-1 Ohira-machi Kawatsure, 329-4498 Tochigi, Tochigi, Japan.
[Yamaguchi, Takehiko] Dokkyo Medical University, Koshigaya Hospital, Department of Pathology, 2-1-50 Minami-Koshigaya, 343-8555 Koshigaya, Saitama, Japan.
[Kawai, Shigeo] Tochigi Medical Center Shimotsuga Hospital, Department of Pathology, 420-1 Ohira-machi Kawatsure, 329-4498 Tochigi, Tochigi, Japan.
RP Yonekura, S (reprint author), Tochigi Medical Center Shimotsuga Hospital, Department of Pathology, 329-4498 Tochigi, Japan.
EM yonechian@gmail.com
CR Sylvester RJ et al, 2006, Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49(3):466–477
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Lombard AP, Mudryj M(2015, The emerging role of the androgen receptor in bladder cancer. Endocr Relat Cancer 22(5):R265–R277
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Wu S et al, 2013, Somatic mutation of the androgen receptor gene is not associated with transitional cell carcinoma: a Bnegative^ study by whole-exome sequencing analysis. Eur Urol 64(6): 1018–1019
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 987
EP 994
DI 10.1007/s12253-018-0431-7
PG 8
ER
PT J
AU Koszo, R
Varga, L
Fodor, E
Kahan, Zs
Cserhati, A
Hideghety, K
Egyud, Zs
Szabo, Cs
Borzasi, E
Szabo, D
Mullner, K
Varga, Z
Maraz, A
AF Koszo, Renata
Varga, Linda
Fodor, Emese
Kahan, Zsuzsanna
Cserhati, Adrienne
Hideghety, Katalin
Egyud, Zsofia
Szabo, Csilla
Borzasi, Emoke
Szabo, Dorottya
Mullner, Kitti
Varga, Zoltan
Maraz, Aniko
TI Prone Positioning on a Belly Board Decreases Rectal and Bowel Doses in Pelvic Intensity-Modulated Radiation Therapy (IMRT) for Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; IMRT; Prone; Belly board; Small bowel; Rectum
ID Prostate cancer; IMRT; Prone; Belly board; Small bowel; Rectum
AB The presence of normal tissues in the irradiated volume limits dose escalation during pelvic radiotherapy (RT) for prostate cancer. Supine and prone positions on a belly board were compared by analyzing the exposure of organs at risk (OARs) using intensity modulated RT (IMRT). The prospective trial included 55 high risk, localized or locally advanced prostate cancer patients, receiving definitive image-guided RT. Computed tomography scanning for irradiation planning was carried out in both positions. Gross tumor volume, clinical and planning target volumes (PTV) and OARs were delineated, defining subprostatic and periprostatic rectal subsegments. At the height of the largest antero-posterior (AP) diameter of the prostate, rectal diameters and distance from the posterior prostate wall were measured. IMRT plans were generated. Normal tissue exposure and structure volumes were compared between supine and prone plans using paired t-test. In the volumes of the prostate, PTV, colon and small bowel, no significant differences were found. In prone position, all rectal volumes, diameters, and rectum–prostate distance were significantly higher, the irradiated colon and small bowel volume was lower in dose ranges of 20–40 Gy, and the exposure to all rectal segments was more favorable in 40–75 Gy dose ranges. No significant difference was found in the exposure of other OARs. Prone positioning on a belly board is an appropriate positioning method aiming rectum and bowel protection during pelvic IMRT of prostate cancer. The relative reduction in rectal exposure might be a consequence of the slight departure between the prostate and rectal wall.
C1 [Koszo, Renata] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Varga, Linda] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Fodor, Emese] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Cserhati, Adrienne] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Hideghety, Katalin] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Egyud, Zsofia] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Szabo, Csilla] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Borzasi, Emoke] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Szabo, Dorottya] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Mullner, Kitti] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
[Maraz, Aniko] University of Szeged, Department of Oncotherapy, Koranyi Alley 12, H-6720 Szeged, Hungary.
RP Koszo, R (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM koszorenata@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 995
EP 1002
DI 10.1007/s12253-018-0436-2
PG 8
ER
PT J
AU Chen, YT
Tsai, HP
Wu, ChCh
Chen, ChY
Chai, ChY
Kwan, AL
AF Chen, Yi-Ting
Tsai, Hung-Pei
Wu, Chun-Chieh
Chen, Chiao-Yun
Chai, Chee-Yin
Kwan, Aij-Lie
TI High-level Sp1 is Associated with Proliferation, Invasion, and Poor Prognosis in Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Astrocytoma; Specificity protein 1; WHO grade; Immunohistochemistry staining; Apoptosis
ID Astrocytoma; Specificity protein 1; WHO grade; Immunohistochemistry staining; Apoptosis
AB Astrocytoma is the most common and the most lethal primary brain tumor in adults. Grade IV glioblastoma is usually refractory to currently available surgical, chemotherapeutic, and radiotherapeutic treatments. The Specificity protein 1 (Sp1) transcription factor is known to regulate tumorigenesis in many cancers. The aim of this study was to investigate the clinicopathologic role of Sp1 protein in the carcinogenesis of astrocytoma. This study analyzed 98 astrocytoma cases treated at Kaohsiung Medical University Hospital during 2002–2012. Clinicopathologic parameters associated with Sp1 were analyzed by chi-square test, Kaplan-Meier analysis, and Cox regression analyses. In vitro proliferation, invasion, and migration were compared between nonsiRNA groups and Sp1 siRNA groups. In glioblastoma cells treated with Sp1 siRNA, Western blot was also used to detect expressions of Sp1, Ki-67, VEGF, cyclin D1, E-cadherin, cleaved caspase-3 and Bax proteins. Expression of Sp1 was significantly associated with WHO grade (p = 0.005) and with overall survival time (p < 0.001). Multivariate analysis further revealed that prognosis of astrocytoma was significantly associated with Sp1 expression (p = 0.036) and IDH-1 expression (p < 0.001). In vitro silencing of Sp1 downregulated Sp1, Ki-67, and cyclin D1 but upregulated E-cadherin, Bax, and cleaved caspase-3. These data suggest that Sp1 is a potential prognostic marker and therapeutic target in astrocytoma.
C1 [Chen, Yi-Ting] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
[Tsai, Hung-Pei] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Department of NeurosurgeryKaohsiung, Taiwan, Republic of China.
[Wu, Chun-Chieh] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
[Chen, Chiao-Yun] Kaohsiung Medical University, College of Medicine, Faculty of Medicine, Department of RadiologyKaohsiung, Taiwan, Republic of China.
[Chai, Chee-Yin] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
[Kwan, Aij-Lie] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
RP Chai, ChY (reprint author), Kaohsiung Medical University, College of Medicine, Department of Pathology, Kaohsiung, Taiwan, Republic of China.
EM cychai@kmu.edu.tw
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1003
EP 1013
DI 10.1007/s12253-018-0422-8
PG 11
ER
PT J
AU Kiss, N
Haluszka, D
Lorincz, K
Gyongyosi, N
Bozsanyi, Sz
Banvolgyi, A
Szipocs, R
Wikonkal, N
AF Kiss, Norbert
Haluszka, Dora
Lorincz, Kende
Gyongyosi, Nora
Bozsanyi, Szabolcs
Banvolgyi, Andras
Szipocs, Robert
Wikonkal, Norbert
TI Quantitative Analysis on Ex Vivo Nonlinear Microscopy Images of Basal Cell Carcinoma Samples in Comparison to Healthy Skin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Basal cell carcinoma; Nonlinear microscopy; Second-harmonic generation; Collagen structure; Quantitative analysis
ID Basal cell carcinoma; Nonlinear microscopy; Second-harmonic generation; Collagen structure; Quantitative analysis
AB Basal cell carcinoma (BCC) is the most frequent malignant neoplasm in the Caucasian population. There are several therapeutic options for BCC, but surgical excision is considered gold standard treatment. As BCCs often have poorly defined borders, the clinical assessment of the tumor margins can be challenging. Therefore, there is an increasing demand for efficient in vivo imaging techniques for the evaluation of tumor borders prior to and during surgeries. In the near future, nonlinear microscopy techniques might meet this demand.We measured the two-photon excitation fluorescence (TPEF) signal of nicotinamide adenine dinucleotide hydride (NADH) and elastin and second harmonic generation (SHG) signal of collagen on 10 ex vivo healthy control and BCC skin samples and compared the images by different quantitative image analysis methods. These included integrated optical density (IOD) measurements on TPEF and SHG images and application of fast Fourier transform (FFT), CT-FIRE and CurveAlign algorithms on SHG images to evaluate the collagen structure. In the BCC samples, we found significantly lower IOD of both the TPEF and SHG signals and higher collagen orientation index utilizing FFT. CT-FIRE algorithm revealed increased collagen fiber length and decreased fiber angle while CurveAlign detected higher fiber alignment of collagen fibers in BCC. These results are in line with previous findings which describe pronounced changes in the collagen structure of BCC. In the future, these novel image analysis methods could be integrated in handheld nonlinear microscope systems, for sensitive and specific identification of BCC.
C1 [Kiss, Norbert] Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
[Haluszka, Dora] Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
[Lorincz, Kende] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Gyongyosi, Nora] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Bozsanyi, Szabolcs] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Banvolgyi, Andras] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Szipocs, Robert] Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
[Wikonkal, Norbert] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
RP Szipocs, R (reprint author), Wigner RCP, Institute for Solid State Physics and Optics, H-1525 Budapest, Hungary.
EM r.szipocs@szipocs.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1015
EP 1021
DI 10.1007/s12253-018-0445-1
PG 7
ER
PT J
AU Decsi, G
Soki, J
Pap, B
Dobra, G
Harmati, M
Kormondi, S
Pankotai, T
Braunitzer, G
Minarovits, J
Sonkodi, I
Urban, E
Nemeth, BI
Nagy, K
Buzas, K
AF Decsi, Gabor
Soki, Jozsef
Pap, Bernadett
Dobra, Gabriella
Harmati, Maria
Kormondi, Sandor
Pankotai, Tibor
Braunitzer, Gabor
Minarovits, Janos
Sonkodi, Istvan
Urban, Edit
Nemeth, Balazs Istvan
Nagy, Katalin
Buzas, Krisztina
TI Chicken or the Egg: Microbial Alterations in Biopsy Samples of Patients with Oral Potentially Malignant Disorders
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OPMD; Oral microbiome; Metagenome sequencing; Lichen; Leukoplakia
ID OPMD; Oral microbiome; Metagenome sequencing; Lichen; Leukoplakia
AB Oral carcinogenesis often leads to the alteration of the microbiota at the site of the tumor, but data are scarce regarding the microbial communities of oral potentially malignant disorders (OPMDs). Punch biopsies were taken from healthy and nonhealthy mucosa of OPMD patients to analyze the microbiome using metagenome sequencing. In healthy oral mucosa biopsies the bacterial phyla Firmicutes, Fusobacteria, Proteobacteria, Actinobacteria and Bacteroidetes were detected by Ion Torrent sequencing. The same phyla as well as the phyla Fibrobacteres and Spirochaetes were present in the OPMD biopsies. On the species level, there were 10 bacterial species unique to the healthy tissue and 35 species unique to the OPMD lesions whereas eight species were detected in both samples. We observed that the relative abundance of Streptococcus mitis decreased in the OPMD lesions compared to the uninvolved tissue. In contrast, the relative abundance of Fusobacterium nucleatum, implicated in carcinogenesis, was elevated in OPMD.We detected markedly increased bacterial diversity in the OPMD lesions compared to the healthy oral mucosa. The ratio of S. mitis and F. nucleatum are characteristically altered in the OPMD lesions compared to the healthy mucosa.
C1 [Decsi, Gabor] University of Szeged, Faculty of Dentistry, Department of Oral Surgery, Tisza Lajos krt. 64, H-6720 Szeged, Hungary.
[Soki, Jozsef] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Institute of Clinical Microbiology, Semmelweis u. 6, H-6725 Szeged, Hungary.
[Pap, Bernadett] Hungarian Academy of Sciences, Biological Research Center, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Dobra, Gabriella] Hungarian Academy of Sciences, Biological Research Center, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Harmati, Maria] Hungarian Academy of Sciences, Biological Research Center, Temesvari krt. 62, H-6726 Szeged, Hungary.
[Kormondi, Sandor] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Department of Traumatology, Semmelweis u. 6, H-6725 Szeged, Hungary.
[Pankotai, Tibor] University of Szeged, Department of Medical Chemistry, Kozep fasor 52, H-6726 Szeged, Hungary.
[Braunitzer, Gabor] dicomLAB Ltd, Pulz u. 46/b, H-6724 Szeged, Hungary.
[Minarovits, Janos] University of Szeged, Faculty of Dentistry, Department of Oral Biology and Experimental Dental Research, Tisza Lajos krt. 64, H-6720 Szeged, Hungary.
[Sonkodi, Istvan] University of Szeged, Faculty of Dentistry, Department of Oral Surgery, Tisza Lajos krt. 64, H-6720 Szeged, Hungary.
[Urban, Edit] University of Szeged, Albert Szent-Gyorgyi Clinical Centre, Institute of Clinical Microbiology, Semmelweis u. 6, H-6725 Szeged, Hungary.
[Nemeth, Balazs Istvan] University of Szeged, Department of Dermatology and Allergology, H-6720 Szeged, Hungary.
[Nagy, Katalin] University of Szeged, Faculty of Dentistry, Department of Oral Surgery, Tisza Lajos krt. 64, H-6720 Szeged, Hungary.
[Buzas, Krisztina] Hungarian Academy of Sciences, Biological Research Center, Temesvari krt. 62, H-6726 Szeged, Hungary.
RP Buzas, K (reprint author), Hungarian Academy of Sciences, Biological Research Center, H-6726 Szeged, Hungary.
EM kr.buzas@gmail.com;buzas.krisztina@brc.mta.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1023
EP 1033
DI 10.1007/s12253-018-0457-x
PG 11
ER
PT J
AU Mlak, R
Krawczyk, P
Homa-Mlak, I
Powrozek, T
Ciesielka, M
Koziol, P
Milanowski, J
Malecka-Massalska, T
AF Mlak, Radoslaw
Krawczyk, Pawel
Homa-Mlak, Iwona
Powrozek, Tomasz
Ciesielka, Marzanna
Koziol, Piotr
Milanowski, Janusz
Malecka-Massalska, Teresa
TI Predictive Value of Single Nucleotide Polymorphisms of ERCC1, XPA, XPC, XPD and XPG Genes, Involved in NER Mechanism in Patients with Advanced NSCLC Treated with Cisplatin and Gemcitabine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Polymorphism; DNA repair; XPD; chemotherapy
ID Non-small cell lung cancer; Polymorphism; DNA repair; XPD; chemotherapy
AB The combination of cisplatin and gemcitabine is still one of the most frequently used first-line chemotherapy scheme in patients with advanced non-small cell lung cancer (NSCLC), in which tyrosine kinase inhibitors (TKIs) cannot be administered. Unfortunately, more than half of the patients have no benefit from chemotherapy but are still exposed to its toxic effects. Therefore, single nucleotide polymorphisms (SNPs) in the genes involved in nucleotide excision repair (NER) mechanism may be a potential predictive factor of efficiency of cytostatic based chemotherapy. The aim of the study was to evaluate the correlation between SNPs of the genes involved in NER mechanism and the effectiveness of chemotherapy based on cisplatin and gemcitabine in patients with advanced NSCLC. The study group included 91 NSCLC patients treated with first-line chemotherapy using cisplatin and gemcitabine. Genotyping was carried out using a mini-sequencing technique (SNaPshot™ PCR). The median progression-free survival (PFS) was significantly shorter in carriers of CC genotype of the XPD/ERCC2 (2251A > C) gene compared to patients with AA/AC genotypes (2 vs. 4.5 months; p = 0.0444; HR = 3.19, 95% CI:1.03–9.91). Rare CC genotype of XPD/ERCC2 gene, may be considered as an unfavorable predictive factor for chemotherapy based on cisplatin and gemcitabine in patients with advanced NSCLC.
C1 [Mlak, Radoslaw] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Krawczyk, Pawel] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Homa-Mlak, Iwona] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Powrozek, Tomasz] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
[Ciesielka, Marzanna] Medical University of Lublin, Department of Forensic Medicine, Jaczewskiego 8b, 20-090 Lublin, Poland.
[Koziol, Piotr] Medical University of Lublin, Department of Forensic Medicine, Jaczewskiego 8b, 20-090 Lublin, Poland.
[Milanowski, Janusz] Medical University of Lublin, Department of Pneumonology, Oncology and Allergology, Jaczewskiego 8, 20-954 Lublin, Poland.
[Malecka-Massalska, Teresa] Medical University of Lublin, Department of Human Physiology, Radziwillowska 11, 20-080 Lublin, Poland.
RP Mlak, R (reprint author), Medical University of Lublin, Department of Human Physiology, 20-080 Lublin, Poland.
EM radoslaw.mlak@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1035
EP 1045
DI 10.1007/s12253-018-0459-8
PG 11
ER
PT J
AU Carvalho, CdA
Melendez, EM
Sabato, dSC
Palmero, IE
Arantes, MRBL
Neto, SC
Carvalho, LA
AF Carvalho, Carolina de Ana
Melendez, Eliseo Matias
Sabato, da Silva Cristina
Palmero, Inez Edenir
Arantes, Maria Rebolho Batista Lidia
Neto, Scapulatempo Cristovam
Carvalho, Lopes Andre
TI Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous Cell Carcinoma Samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oropharyngeal cancer; Human papillomavirus; Methylation; Mutation; Prognosis
ID Oropharyngeal cancer; Human papillomavirus; Methylation; Mutation; Prognosis
AB A better understanding of the clinical and molecular features of oropharyngeal squamous cell carcinomas (OPSCC) may help in the development of strategies for a better patient management, improving survival rates. This retrospective study conducted a clinical and molecular characterization of surgically treated OPSCC samples. Paraffin-embedded samples from a series of cases were screened for high-risk (HR) human papillomavirus (HPV) infection, methylation of a 5-gene panel, p53 expression, and TP53 mutation. The study was conducted at Barretos Cancer Hospital. Twenty-five surgically treated OPSCC with available tissue were included in the study. Samples were classified according to HPV status and molecular features and some of these characteristics were associated to clinical data. Twenty percent of the cases were HR-HPV positive and 62.5% presented TP53 mutations. DAPK hypermethylation was associated with HPV status (p = 0.023), while methylated CCNA1 was inversely related to TP53 mutations in primary tumors (p = 0.042) and associated with a better disease-free survival (22.3% vs. 100.0%; p = 0.028) and overall survival (8.0% vs. 100.0%; p = 0.012). The results show differences regarding molecular and clinical characteristics in the oropharynx cases identified that should be validated in more cases to confirm whether these differences are able to classify patients according to outcome and help in a more thorough patient management.
C1 [Carvalho, Carolina de Ana] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Melendez, Eliseo Matias] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Sabato, da Silva Cristina] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Palmero, Inez Edenir] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Arantes, Maria Rebolho Batista Lidia] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Neto, Scapulatempo Cristovam] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
[Carvalho, Lopes Andre] Barretos Cancer Hospital, Molecular Oncology Research Center, Rua Antenor Duarte Vilela, 1331, 14784-400 Barretos, SP, Brazil.
RP Carvalho, CdA (reprint author), Barretos Cancer Hospital, Molecular Oncology Research Center, 14784-400 Barretos, Brazil.
EM anacarol.oak@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1047
EP 1058
DI 10.1007/s12253-018-0462-0
PG 12
ER
PT J
AU Temraz, S
Shamseddine, A
Mukherji, D
Charafeddine, M
Tfayli, A
Assi, H
Hammoud, SM
Makki, I
Nassif, S
AF Temraz, Sally
Shamseddine, Ali
Mukherji, Deborah
Charafeddine, Maya
Tfayli, Arafat
Assi, Hazem
Hammoud, Salim Miza
Makki, Iman
Nassif, Samer
TI Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer: a Single Institution Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic cancer; Ki67; P53; CA19–9; Prognosis
ID Pancreatic cancer; Ki67; P53; CA19–9; Prognosis
AB We investigated the expression patterns of Ki67 and p53 in metastatic pancreatic adenocarcinomas and analyzed their relationship with disease progression-free survival (PFS) and overall survival (OS) in the overall study population and in patients treated with a gemcitabine-containing chemotherapy versus FOLFIRINOX chemotherapy. Patients with histologically confirmed stage IV adenocarcinoma of the pancreas treated at AUBMC were included after obtaining institutional review board approval (IRB ID: IM.ST.05). The ROC was plotted to identify the threshold Ki-67, p53 and CA19–9 value for disease progression, the identified value was further used in Kaplan Meier curves to compare PFS for both groups (gemcitabine versus FOLFIRINOX). A value of p < 0.05 was considered significant in all analyses. On univariate analysis, patients who had a Ki- 67 > 12.5% or a p53 > 15% had significantly shorter PFS (p = 0.034 and p = 0.016, respectively). This effect was restricted to Gemcitabine or gemcitabine-combination treated patients. A decrease in CA19–9 levels 6–8 weeks after chemotherapy of >58% had significantly longer PFS (p = 0.027). On multivariate analysis after controlling for grade, age and P53, Ki-67 remained significant, for every one unit increase in Ki-67 the progression risk increases by 1.017 times. Our study highlights the negative impact of high P53 expression and Ki67 proliferation index on PFS in patients with metastatic pancreatic cancer.
C1 [Temraz, Sally] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Shamseddine, Ali] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Mukherji, Deborah] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Charafeddine, Maya] American University of Beirut Medical Center, Data Management and Clinical Research Unit, Riad El Solh, 110 72020 Beirut, Lebanon.
[Tfayli, Arafat] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Assi, Hazem] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Hammoud, Salim Miza] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Makki, Iman] American University of Beirut Medical Center, Department of Internal Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
[Nassif, Samer] American University of Beirut Medical Center, Department of Pathology and Laboratory Medicine, Riad El Solh, 110 72020 Beirut, Lebanon.
RP Temraz, S (reprint author), American University of Beirut Medical Center, Department of Internal Medicine, 110 72020 Beirut, Lebanon.
EM st29@aub.edu.lb
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1059
EP 1066
DI 10.1007/s12253-018-0464-y
PG 8
ER
PT J
AU Nedjadi, T
Salem, N
Khayyat, D
Al-Sayyad, A
Al-Ammari, A
Al-Maghrabi, J
AF Nedjadi, Taoufik
Salem, Nada
Khayyat, Dareen
Al-Sayyad, Ahmed
Al-Ammari, Adel
Al-Maghrabi, Jaudah
TI Sonic Hedgehog Expression is Associated with Lymph Node Invasion in Urothelial Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Sonic hedgehog; Expression; Lymph node; Prognosis
ID Bladder cancer; Sonic hedgehog; Expression; Lymph node; Prognosis
AB Bladder cancer (BC) is a deadly disease characterized by high recurrence rates and frequent progression to an aggressive phenotype. Dysregulation of various signaling pathways have been implicated in BC tumorigenesis, however, the clinical relevance of sonic hedgehog pathway (Shh) remains under investigated. The aim of the current study was to analyze the prognostic value of Shh expression in patients with bladder carcinoma. Immunohistochemical expression of Shh was performed using tissue microarray with 128 specimens from bladder cancer patients. Kaplan-meier survival was analysed and correlation between Shh protein expression and patients’ clinicopathological parameters wasexamined using Fisher’s exact test. The immuno-staining results revealed that Shh protein exhibits cytoplasmic localization and is expressed in 49% of the analyzed bladder cancer cohort. Our data indicated that high Shh expression significantly correlated with increased lymph node metastasis (p = 0.02), however no association was reported between Shh expression and other clinicopatholigical parameters. High expression of sonic hedgehog was associated with lymph node invasion which may indicate that Shh might play an important role in progression and metastasis of bladder cancer.
C1 [Nedjadi, Taoufik] Ministry of National Guard-Health Affairs, King Abdulaziz Medical City, King Abdullah International Medical Research CentreJeddah, Saudi Arabia.
[Salem, Nada] King Abdulaziz University, Center of Excellence in Genomic Medicine ResearchJeddah, Saudi Arabia.
[Khayyat, Dareen] King Abdulaziz University, King Fahd Medical Research CentreJeddah, Saudi Arabia.
[Al-Sayyad, Ahmed] King Abdulaziz University, Department of UrologyJeddah, Saudi Arabia.
[Al-Ammari, Adel] King Faisal Specialist Hospital & Research Center, Department of UrologyJeddah, Saudi Arabia.
[Al-Maghrabi, Jaudah] King Abdulaziz University, Department of PathologyJeddah, Saudi Arabia.
RP Nedjadi, T (reprint author), Ministry of National Guard-Health Affairs, King Abdulaziz Medical City, King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia.
EM nedjadita@ngha.med.sa
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1067
EP 1073
DI 10.1007/s12253-018-0477-6
PG 7
ER
PT J
AU Han, RL
Wang, J
Zhang, FJ
Zhao, N
Gao, BL
AF Han, Ruo-Ling
Wang, Jin
Zhang, Feng-Juan
Zhao, Na
Gao, Bu-Lang
TI Ultrasound Risk Assessment Combined with Molecular Markers of Galectin-3, c-MET, HBME-1 and CK19 for Diagnosis of Malignant and Benign Thyroid Nodules
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ultrasound; Malignancy risk; Thyroid nodules; Molecular marker; Diagnosis
ID Ultrasound; Malignancy risk; Thyroid nodules; Molecular marker; Diagnosis
AB To investigate the effect of ultrasound combined with expression of Galectin-3, c-Met, HBME-1 and CK19 in differentiating malignant from benign thyroid nodules. Forty-six patients with thyroid nodules were studied with ultrasound and immunohistochemical staining of excised thyroid nodules. The data were classified and compared. The immunohistochemical staining revealed 8 benign and 41 malignant thyroid lesions. In ultrasound risk assessment, the malignancy risk was low in four nodules, medium in five and high in 37 with lymphatic metastasis in 26. A significant (P < 0.05) association existed in the expression of Galectin-3 with nodule boundary and lymphatic metastasis, in HBME-1 with nodule micro-calcification and in c-Met with nodule micro-calcification and lymphatic metastasis. CK19 expression was not significantly (P > 0.05) associated with any of ultrasound features of nodule. Galectin-3, c-Met, HBME-1 and CK19 were significantly (P < 0.05) different in malignant and benign thyroid lesions, with a significant (P < 0.01) tendency in all the molecular markers in predicting the malignant from benign lesions. The ultrasound characteristics could significantly (P < 0.001) predict malignant nodules with a significant (P < 0.05) prediction tendency. The scores of Galectin-3, c-Met and CK19 significantly (P < 0.05) increased with increase of ultrasound malignancy risk degree. In malignant and benign lesions differentiated by ultrasound, no significant (P > 0.05) difference existed in HBME-1 expression, however, with ultrasound malignancy risk increase, the score of HBME-1 expression increased significantly (P = 0.03). Galectin-3, c-Met, HBME-1 and CK19 have significantly greater expressions in thyroid malignant than benign lesions and their expression increases with increase of ultrasound malignancy risk. The combination of both ultrasound and molecular markers can be used to differentiate malignant and benign thyroid lesions.
C1 [Han, Ruo-Ling] The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Department of Ultrasound, 12 Jiankang Road, 050011 Shijiazhuang, Hebei Province, China.
[Wang, Jin] The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Department of Ultrasound, 12 Jiankang Road, 050011 Shijiazhuang, Hebei Province, China.
[Zhang, Feng-Juan] The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Department of Ultrasound, 12 Jiankang Road, 050011 Shijiazhuang, Hebei Province, China.
[Zhao, Na] The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Department of Ultrasound, 12 Jiankang Road, 050011 Shijiazhuang, Hebei Province, China.
[Gao, Bu-Lang] Henan Provincial People’s Hospital, Department of Interventional TherapyZhengzhou, Henan Province, China.
RP Han, RL (reprint author), The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Department of Ultrasound, 050011 Shijiazhuang, China.
EM hrl-63523@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1075
EP 1081
DI 10.1007/s12253-018-0485-6
PG 7
ER
PT J
AU Miyazawa, H
Kato, K
Kobayashi, Y
Hirai, M
Kimura, I
Kitahara, H
Noguchi, N
Nakamura, H
Kawashiri, Sh
AF Miyazawa, Hiroki
Kato, Koroku
Kobayashi, Yutaka
Hirai, Mariko
Kimura, Iyo
Kitahara, Hiroko
Noguchi, Natsuyo
Nakamura, Hiroyuki
Kawashiri, Shuichi
TI Clinicopathological Significance of the ET Axis in Human Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endothelin; ET-1; ETAR; ET-axis; Oral squamous cell carcinoma; Prognosis
ID Endothelin; ET-1; ETAR; ET-axis; Oral squamous cell carcinoma; Prognosis
AB The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ETAR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cellmalignancy and the expressions of ET-1 and ETAR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ETAR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.
C1 [Miyazawa, Hiroki] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kato, Koroku] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kobayashi, Yutaka] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Hirai, Mariko] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kimura, Iyo] Nanto Municipal Hospital, Department of Oral and Maxillofacial Surgery, 938 Inami, 932-0211 Nanto, Japan.
[Kitahara, Hiroko] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Noguchi, Natsuyo] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Nakamura, Hiroyuki] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kawashiri, Shuichi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
RP Kato, K (reprint author), Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 920-8641 Kanazawa, Japan.
EM k-koroku@oral.m.kanazawa-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1083
EP 1089
DI 10.1007/s12253-018-0514-5
PG 7
ER
PT J
AU Liu, Y
Guan, J
Chen, X
AF Liu, Yang
Guan, Jianzhong
Chen, Xiaotian
TI Identification of Differentially Expressed Genes under the Regulation of Transcription Factors in Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Microarray dataset; Differentialy expressed genes; Transcription factors
ID Osteosarcoma; Microarray dataset; Differentialy expressed genes; Transcription factors
AB The present study was to investigate and identify the differentially expressed genes (DEGs) in the transcriptional regulatory network of osteosarcoma (OS). The gene expression dataset from Gene Expression Omnibus (GEO) datasets was downloaded. DEGs were identified and their functional annotation was also conducted. In addition, differentially expressed transcription factors (TFs) and the regulatory genes were identified. The electronic validation was used to verify the expression of selected genes. The integrated analysis led to 932 DEGs. The results of functional annotation indicated that these DEGs significantly enriched in the p53 signaling pathway, Jak-STAT signaling pathway and Wnt signaling pathway. ZNF354C, NFIC, NFATC2, SP2, FOXO3, EGR1, ZEB1, RREB1, EGR2 and SRF were covered by most TFs. The expression levels of NFIC and EGR2 in electronic validation were compatible with our bio-informatics result. In conclusion, the deregulation of these genes may provide valuable information in understanding the underlying molecular mechanism in the OS.
C1 [Liu, Yang] The First Affiliated Hospital of Bengbu Medical College, Department of Orthopaedics, No. 287, ChangHuai Road, 233004 Bengbu, Anhui Province, China.
[Guan, Jianzhong] The First Affiliated Hospital of Bengbu Medical College, Department of Orthopaedics, No. 287, ChangHuai Road, 233004 Bengbu, Anhui Province, China.
[Chen, Xiaotian] The First Affiliated Hospital of Bengbu Medical College, Department of Orthopaedics, No. 287, ChangHuai Road, 233004 Bengbu, Anhui Province, China.
RP Guan, J (reprint author), The First Affiliated Hospital of Bengbu Medical College, Department of Orthopaedics, 233004 Bengbu, China.
EM guanjianzhongah@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1091
EP 1102
DI 10.1007/s12253-018-0519-0
PG 12
ER
PT J
AU Lendvai, G
Szekerczes, T
Gyongyosi, B
Schlachter, K
Kontsek, E
Pesti, A
Patonai, A
Werling, K
Kovalszky, I
Schaff, Zs
Kiss, A
AF Lendvai, Gabor
Szekerczes, Timea
Gyongyosi, Benedek
Schlachter, Krisztina
Kontsek, Endre
Pesti, Adrian
Patonai, Attila
Werling, Klara
Kovalszky, Ilona
Schaff, Zsuzsa
Kiss, Andras
TI MicroRNA Expression in Focal Nodular Hyperplasia in Comparison with Cirrhosis and Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Focal nodular hyperplasia; Hepatic cirrhosis; Hepatocellular carcinoma; microRNA; Chronic hepatitis C
ID Focal nodular hyperplasia; Hepatic cirrhosis; Hepatocellular carcinoma; microRNA; Chronic hepatitis C
AB The liver disease focal nodular hyperplasia (FNH) has several histological features that resemble hepatic cirrhosis. Since cirrhosis may develop further into hepatocellular carcinoma (HCC) contrary to FNH, the aim of the present study was to identify microRNAs (miRNA), which, by their altered expression levels, may be associated with the benign, tumor-like nature of FNH. Altogether 106 surgically removed formalin-fixed paraffin-embedded liver samples were selected, including 22 FNH, 45 cirrhosis, 24 HCC and 15 normal liver tissues. Etiology of the cases of cirrhosis and HCC includes hepatitis C and alcoholism and the HCC cases developed in cirrhotic livers. Relative expression levels of 14 miRNAs were determined using TaqMan MicroRNA Assays. In comparison to normal liver, the levels of miR-34a and miR-224 were elevated not only in FNH but also in cirrhosis and HCC, while the expression of miR-17-5p, miR-18a and miR-210 was decreased in FNH. Further, the levels of miR- 21 and miR-222 were increased in cirrhosis and HCC but were decreased in FNH and the expression of miR-17-5p, miR-18a, miR-195 and miR-210 was decreased in FNH as compared with cirrhosis and/or HCC. In conclusion, the elevation of miR-34a and miR-224 may be associated with both benign and malignant proliferative processes, nevertheless the increased expression of oncomiRs miR-21 and miR-222 in cirrhosis and HCC but not in FNH may be related to malignant processes of the liver. The decreased levels of miR-18a, miR-195 and miR-210 may further differentiate FNH from cirrhosis, reflecting the different pathogenesis of these two entities contrary to some histologically similar features.
C1 [Lendvai, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Gyongyosi, Benedek] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Schlachter, Krisztina] National Institute of Oncology, Department of Diagnostic Pathology, 1122 Budapest, Hungary.
[Kontsek, Endre] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Pesti, Adrian] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Patonai, Attila] Semmelweis University, Department of Transplantation and Surgery, 1082 Budapest, Hungary.
[Werling, Klara] Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
RP Lendvai, G (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM lendvai.gabor@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1103
EP 1109
DI 10.1007/s12253-018-0528-z
PG 7
ER
PT J
AU Yang, XH
Liu, L
Hu, YJ
Zhang, P
Hu, QG
AF Yang, Xi-Hu
Liu, Liu
Hu, Yong-Jie
Zhang, Ping
Hu, Qin-Gang
TI Co-expression of XIAP and CIAP1 Play Synergistic Effect on Patient’s Prognosis in Head and Neck Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck; Squamous cell carcinoma; XIAP and CIAP1; Prognosis
ID Head and neck; Squamous cell carcinoma; XIAP and CIAP1; Prognosis
AB To explore the influence of chemotherapy on prognosis of Head and Neck Squamous Cell Carcinoma (HNSCC) and the relationship between XIAP and CIAP1 co-expression and the prognosis in HNSCC. 129 patients were recruited in our study, they were divided into two groups, neoadjuvant group (n = 60) and non-neoadjuvant group (n = 69). Expression level of XIAP and CIAP1 were examed in neoadjuvant group, and was correlated with clinical outcomes of the patients. The unselected patients were not benefit from neoadjuvant chemotherapy. Moreover, the patients whose tumors co-express high level of XIAP and CIAP1 presented poorer overall and disease-free survival rates than those whose tumors co-express low level of XIAP and CIAP1 (overall survival P < 0.001, disease-free survival P < 0.001). Our results validate that individual chemotherapy is important for HNSCC, and co-expression of XIAP and CIAP1 prompted a worse prognosis.
C1 [Yang, Xi-Hu] Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial Surgery, 210000 Nanjing, Jiangsu, China.
[Liu, Liu] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial Surgery, 200011 Shanghai, China.
[Hu, Yong-Jie] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial Surgery, 200011 Shanghai, China.
[Zhang, Ping] Boston University, Henry M. Goldman School of Dental Medicine, 02125 Boston, MA, USA.
[Hu, Qin-Gang] Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial Surgery, 210000 Nanjing, Jiangsu, China.
RP Hu, QG (reprint author), Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial Surgery, 210000 Nanjing, China.
EM qinganghu@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1111
EP 1116
DI 10.1007/s12253-018-0533-2
PG 6
ER
PT J
AU Lambert, A
Salleron, J
Lion, M
Rouyer, M
Lozano, N
Leroux, A
Merlin, JL
Harle, A
AF Lambert, Aurelien
Salleron, Julia
Lion, M
Rouyer, Marie
Lozano, Nicolas
Leroux, Agnes
Merlin, Jean-Louis
Harle, Alexandre
TI Comparison of Three Real-Time PCR Assays for the Detection of PIK3CA Somatic Mutations in Formalin-Fixed Paraffin Embedded Tissues of Patients with Breast Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PIK3CA; Real-time PCR; Breast cancer; PI3K; ARMS; HRM
ID PIK3CA; Real-time PCR; Breast cancer; PI3K; ARMS; HRM
AB Breast cancer is the leading cause of cancer-related death in women worldwide. Mutations of the PIK3CA gene are found in approximately 25% of breast carcinomas and are reported as activators of the PI3K/AKT/mTOR pathway. This study aims to compare three assays for the somatic mutation detection of PIK3CA gene in FFPE tissues of patients with breast cancer. We compared Cobas® PIK3CA Mutation Test (Roche Diagnostics, Meylan, France), PCR amplification-refractory mutation system Scorpions® (ARMS) and High-Resolution Melting PCR assay (HRM) for the detection of PIK3CA mutations. Discrepant samples were assessed using Next Generation Sequencing (NGS). 46 FFPE breast carcinomas samples of patients treated for breast cancer have been assessed for PIK3CA mutations using the three PCR assays. Among the 46 samples, 17 (37.8%), 13 (28.36%) and 19 (41.3%) had a PIK3CA mutation, with Cobas®, ARMS and HRM assays respectively. Three different mutations of PIK3CA have been detected for one sample. Calculated kappa were 0.95[0.86;1] between Cobas® and HRM, 0.75[0.55;0.95] between Cobas® and ARMS and 0.72[0.51;0.92] between HRM and ARMS. Five samples were found with discrepant results. Our study shows that the Cobas® assay is suitable for PIK3CA mutation assessment in patients with breast cancer. HRM assay is also suitable for PIK3CA mutation assessment but requires a mutation characterization with a specific assay.
C1 [Lambert, Aurelien] Institut de Cancerologie de Lorraine, Departement d’Oncologie Medicale, 54519 Vandoeuvre les Nancy, France.
[Salleron, Julia] Institut de Cancerologie de Lorraine, Departement de Biostatistiques, 54519 Vandoeuvre les Nancy, France.
[Lion, M] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
[Rouyer, Marie] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
[Lozano, Nicolas] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
[Leroux, Agnes] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
[Merlin, Jean-Louis] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
[Harle, Alexandre] Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 6 avenue de Bourgogne, 54519 Vandoeuvre les Nancy, France.
RP Harle, A (reprint author), Universite de Lorraine, Institut de Cancerologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, 54519 Vandoeuvre les Nancy, France.
EM a.harle@nancy.unicancer.fr
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Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, Swain SM, 2014, Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol 32(33):3753–3761. , DOI 10.1200/jco.2013. 54.5384
Harle A, Lion M, Lozano N, Husson M, Harter V, Genin P, Merlin JL, 2013, Analysis of PIK3CA exon 9 and 20 mutations in breast cancers using PCR-HRM and PCR-ARMS: correlation with clinicopathological criteria. Oncol Rep 29(3):1043–1052. https://doi. org/10.3892/or.2013.2229
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1117
EP 1123
DI 10.1007/s12253-018-0538-x
PG 7
ER
PT J
AU Zhu, Y
Sun, X
Lin, J
Zhang, T
Liu, X
Shen, X
AF Zhu, Yi
Sun, Xiangwei
Lin, Ji
Zhang, Teming
Liu, Xin
Shen, Xian
TI Investigating Potential Molecular Mechanisms of Carcinogenesis and Genes as Biomarkers for Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; GEO data; lncRNAs; Integrated bioinformatics; Regulatory network
ID Gastric cancer; GEO data; lncRNAs; Integrated bioinformatics; Regulatory network
AB Gastric cancer, as the fifth most common malignancy worldwide, is a deadly disease afflicting nearly a million people. Researchers have devoted much to study the mechanisms of carcinogenesis and progression, but the exact information of tumor initiation and progression is remained largely unknown. Here, we hypothesized several differentially expressed genes and possible pathways by employing integrated bioinformatics analysis. We fully analyzed four gastric cancer-related microarray datasets to screen differentially expressed mRNAs (DEMs), miRNAs (DEMis) and lncRNAs (DELs). The functional enrichment analysis was deeply construed, PPI network and ceRNA regulatory network were constructed to investigate potential mechanisms of tumorigenesis and progression. Furthermore, survival analysis was performed to identify critical lncRNAs that may significantly affect pathogenesis of gastric cancer. QRT-PCR was applied to verify our result.We identified two hub subnetworks that may explain the progression, metastasis and poor prognosis of gastric cancer. Meanwhile, several potential significant lncRNAs were identified. In summary, we ascertained several significantly changed KEGG pathways in the tumor initiation and progression. We also hypothesized several lncRNAs that contribute to poor prognosis of gastric cancer via integrated bioinformatics, which deserve further investigation.
C1 [Zhu, Yi] Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, No. 109, Xueyuan West Road, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Sun, Xiangwei] Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, No. 109, Xueyuan West Road, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Lin, Ji] Wenzhou Medical University, First Affiliated HospitalWenzhou, Zhejiang, China.
[Zhang, Teming] Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, No. 109, Xueyuan West Road, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Liu, Xin] Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, No. 109, Xueyuan West Road, Lucheng District, 325000 Wenzhou, Zhejiang, China.
[Shen, Xian] Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, No. 109, Xueyuan West Road, Lucheng District, 325000 Wenzhou, Zhejiang, China.
RP Shen, X (reprint author), Wenzhou Medical University, The Second Affiliated Hospital and Yuying Children’s Hospital, 325000 Wenzhou, China.
EM 13968888872@126.com
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA Cancer J Clin 61(2):69–90
Russo A, Li P, Strong VE, 2017, Differences in the multimodal treatment of gastric cancer: east versus west. J Surg Oncol 115(5): 603–614
Tseng CW, Lin CC, Chen CN, Huang HC, Juan HF, 2011, Integrative network analysis reveals active microRNAs and their functions in gastric cancer. BMC Syst Biol 5:99
Song YX, Sun JX, Zhao JH, Yang YC, Shi JX,Wu ZH, Chen XW, Gao P,Miao ZF,Wang ZN, 2017, Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion. Nat Commun 8(1):289
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da Huang W, Sherman BT, Lempicki RA, 2009, Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13
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MengQ, Yang BY, Liu B,Yang JX, SunY(2018, Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR- 101-3p. Int J Biol Markers 33(2):148–155
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1125
EP 1133
DI 10.1007/s12253-018-0523-4
PG 9
ER
PT J
AU Bellolio, E
Riquelme, I
Riffo-Campos, LA
Rueda, C
Ferreccio, C
Villaseca, M
Brebi, P
Munoz, S
Araya, CJ
AF Bellolio, Enrique
Riquelme, Ismael
Riffo-Campos, L Angela
Rueda, Carlos
Ferreccio, Catterina
Villaseca, Miguel
Brebi, Priscilla
Munoz, Sergio
Araya, Carlos Juan
TI Assessment of Gastritis and Gastric Cancer Risk in the Chilean Population Using the OLGA System
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE The OLGA system; Helicobacter pylori infection; Gastric atrophy; Metaplasia; Gastric cancer; Chilean population
ID The OLGA system; Helicobacter pylori infection; Gastric atrophy; Metaplasia; Gastric cancer; Chilean population
AB Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56 years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.
C1 [Bellolio, Enrique] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Riquelme, Ismael] Universidad Autonoma de Chile, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomedicas, Avenida Alemania 01090, 4810101 Temuco, Chile.
[Riffo-Campos, L Angela] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Rueda, Carlos] Gastroenterologist, Avenida Apoquindo 2880, 7550000 Santiago, Chile.
[Ferreccio, Catterina] Pontificia Universidad Catolica de Chile, School of MedicineSantiago, Chile.
[Villaseca, Miguel] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Brebi, Priscilla] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
[Munoz, Sergio] Universidad de La Frontera, School of Medicine, Department of Public Health, General Jose Miguel Carrera 228, 4781135 Temuco, Chile.
[Araya, Carlos Juan] Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, Avenida Alemania 0458, 4810296 Temuco, Chile.
RP Bellolio, E (reprint author), Universidad de La Frontera, School of Medicine, Department of Pathological Anatomy, 4810296 Temuco, Chile.
EM enrique.bellolio@ufrontera.cl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1135
EP 1142
DI 10.1007/s12253-018-0532-3
PG 8
ER
PT J
AU Zhang, Y
Xu, J
Li, D
Wan, T
Hu, Q
AF Zhang, Yunmei
Xu, Jieru
Li, Dairong
Wan, Tao
Hu, Qianfang
TI Immunocytochemistry Based on a Cell-Type-Specific Aptamer for Rapid Immunostaining of Adenocarcinoma Cells in Clinical Serosal Fluids
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aptamer; Immunocytochemistry; Adenocarcinoma cells; Serosal fluid
ID Aptamer; Immunocytochemistry; Adenocarcinoma cells; Serosal fluid
AB All too often, conventional immunocytochemistry (ICC) via an antibody on cytological samples is limited to a few smears due to scant cellularity. To circumvent these limitations, this study employed a cell-type-specific aptamer as the core tool in ICC protocols for a timely and highly specific ICC diagnosis. S6, an aptamer against A549 lung carcinoma cells, was adopted instead of antibodies in this study for differentiating cancer cells in serosal fluids. Here, we developed three different strategies for discriminating the adenocarcinoma cells in effusion cytology specimens using the S6 aptamer in ICC. These strategies included a biotin-labeled S6 aptamer, an FAM-labeled S6 aptamer, and an activatable S6 aptamer. A total of 112 serosal fluid specimens with known diagnoses were evaluated by all three modes of use of the S6 aptamer. ICC procedures based on biotin-labeled or FAM-labeled S6 aptamers required time-consuming washing to avoid interference from nonspecific adsorption. ICC procedures based on an activatable S6 aptamer probe showed a weak fluorescence signal in the absence of target cells, but the procedures showed a strong fluorescence signal due to alteration of the conformation without any complicated washing steps, in the presence of targets. The specificity and sensitivity are higher in all three different ICC protocols based on the S6 aptamer than those for antibody protocols for differentiating adenocarcinoma cells in clinical effusion cytology. ICC based on cell-type-specific aptamers, instead of on a panel of a set of antibodies, is promising as an auxiliary method for the diagnosis of cancer.
C1 [Zhang, Yunmei] Chongqing Medical University, The Nursing College, 400016 Chongqing, China.
[Xu, Jieru] Chongqing Medical University, The First Affiliated Hospital, Department of Respiratory and Critical Care Medicine, No. 1 YouYi Road, Yuzhong District, 400016 Chongqing, China.
[Li, Dairong] Chongqing Medical University, The First Affiliated Hospital, Department of Respiratory and Critical Care Medicine, No. 1 YouYi Road, Yuzhong District, 400016 Chongqing, China.
[Wan, Tao] Chongqing Medical University, The First Affiliated Hospital, Department of Respiratory and Critical Care Medicine, No. 1 YouYi Road, Yuzhong District, 400016 Chongqing, China.
[Hu, Qianfang] Chongqing Medical University, The First Affiliated Hospital, Department of Respiratory and Critical Care Medicine, No. 1 YouYi Road, Yuzhong District, 400016 Chongqing, China.
RP Li, D (reprint author), Chongqing Medical University, The First Affiliated Hospital, Department of Respiratory and Critical Care Medicine, 400016 Chongqing, China.
EM lidairong-e@yeah.net
CR Wu GP, Zhang SS, Fang CQ, Liu SL, Wang EH, 2008, Immunocytochemical panel for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. Cytopathology 19:212–217. , DOI 10.1111/j.1365-2303. 2008.00559.x
Sriramoju B, Kanwar R, Veedu RN, Kanwar JR, 2015, Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases. Curr Top Med Chem 15:1115–1124. , DOI 10.2174/1568026615666150413153928
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1143
EP 1152
DI 10.1007/s12253-018-0555-9
PG 10
ER
PT J
AU Zombori, T
Cserni, G
AF Zombori, Tamas
Cserni, Gabor
TI Patterns of Regression in Breast Cancer after Primary Systemic Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Primary systemic therapy; Breast cancer; Regression pattern; Molecular subtypes
ID Primary systemic therapy; Breast cancer; Regression pattern; Molecular subtypes
AB Despite national guidelines, the evaluation of effects of primary systemic treatment (PST) in breast cancer is a complex challenge. Our aims were to evaluate the response patterns focusing on correlations of radiological and pathological tumor size, regression heterogeneity in different molecular subtypes, cellularity changes and the incidence of enlarged, multinucleated neoplastic cells related to therapy. Slides of pretreatment biopsies and resection specimens of consecutive cases were reevaluated focusing on heterogeneity of regression per whole slide, and 40x or 100x magnification fields. Alteration in cellularity and the presence of multinucleated tumor giant cells were noted. The correlation of pathological and radiological sizes and their alterations were analyzed by Spearman rank correlation. The present study included 106 tumors. A decrease in size (84.9%) and cellularity (76.4%) was noted in all molecular subtypes. Inhomogeneous regression was found in 45.3%, with minor inhomogeneity in the majority. Scatter pattern regression was seen only in 8 cases (7.5%). Significant correlations were found between the pathological and radiological sizes (p = 0.02), and between the alterations of cellularity and pathological and radiological size (p = 0.04; p = 0.03, respectively). Multinucleated tumor giant cells were noted in 17.9% (n = 19), nearly exclusively in cases treated with PST including taxanes. Regression inhomogeneity following PST is present in about half of the cases, and is not related to molecular subtypes. The evaluation of the maximum area of the tumor bed is recommended for the proper evaluation of regression. Multinucleated tumor giant cells are related to PST including taxane derivate, and may cause upgrading.
C1 [Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1., 6725 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1., 6725 Szeged, Hungary.
RP Zombori, T (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM zomtam@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1153
EP 1161
DI 10.1007/s12253-018-0557-7
PG 9
ER
PT J
AU Carvalho, JM
Laranjo, M
Abrantes, MA
Casalta-Lopes, J
Sarmento-Santos, D
Costa, T
Serambeque, B
Almeida, N
Goncalves, T
Mamede, C
Encarnacao, J
Oliveira, R
Paiva, A
de Carvalho, R
Botelho, F
Oliveira, C
AF Carvalho, Joao Maria
Laranjo, Mafalda
Abrantes, Margarida Ana
Casalta-Lopes, Joao
Sarmento-Santos, Daniela
Costa, Tania
Serambeque, Beatriz
Almeida, Nuno
Goncalves, Telmo
Mamede, Catarina
Encarnacao, Joao
Oliveira, Rui
Paiva, Artur
de Carvalho, Rui
Botelho, Filomena
Oliveira, Carlos
TI Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative Metabolism
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial neoplasms; Neoplastic stem cells; Glucose metabolism
ID Endometrial neoplasms; Neoplastic stem cells; Glucose metabolism
AB This study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β- catenin, fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher 18F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.
C1 [Carvalho, Joao Maria] University of Coimbra, Universitary Clinic of GynecologyCoimbra, Portugal.
[Laranjo, Mafalda] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Abrantes, Margarida Ana] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Casalta-Lopes, Joao] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Sarmento-Santos, Daniela] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Costa, Tania] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Serambeque, Beatriz] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Almeida, Nuno] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Goncalves, Telmo] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Mamede, Catarina] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Encarnacao, Joao] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Oliveira, Rui] Coimbra Hospital and University Centre, Clinical Pathology DepartmentCoimbra, Portugal.
[Paiva, Artur] Coimbra Hospital and Universitary Centre, Flow Cytometry UnitCoimbra, Portugal.
[de Carvalho, Rui] University of Coimbra, Faculty of Science and Technology, Department of Life Sciences, Centre for Functional EcologyCoimbra, Portugal.
[Botelho, Filomena] University of Coimbra, Faculty of Medicine, Biophysics InstituteCoimbra, Portugal.
[Oliveira, Carlos] University of Coimbra, Faculty of Medicine, CIMAGOCoimbra, Portugal.
RP Carvalho, JM (reprint author), University of Coimbra, Universitary Clinic of Gynecology, Coimbra, Portugal.
EM mariajoaosflcarvalho@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1163
EP 1174
DI 10.1007/s12253-018-0535-0
PG 12
ER
PT J
AU Helbig, G
Chromik, K
Wozniczka, K
Kopinska, JA
Boral, K
Dworaczek, M
Koclega, A
Armatys, A
Panz-Klapuch, M
Markiewicz, M
AF Helbig, Grzegorz
Chromik, Karolina
Wozniczka, Krzysztof
Kopinska, J Anna
Boral, Kinga
Dworaczek, Martyna
Koclega, Anna
Armatys, Anna
Panz-Klapuch, Marta
Markiewicz, Miroslaw
TI Real Life Data on Efficacy and Safety of Azacitidine Therapy for Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Azacitidine; Myelodysplastic syndrome; Chronic myelomonocytic leukemia; Acute myeloid leukemia; Results
ID Azacitidine; Myelodysplastic syndrome; Chronic myelomonocytic leukemia; Acute myeloid leukemia; Results
AB The administration of azacitidine (AZA) was found to be more effective than conventional care regimen (CCR) in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) with lower blast count. We designed a study to determine efficacy and safety of AZA therapy in "real life" patients with MDS, CMML and AML. The study included 83 patients (65% male) with a median age at diagnosis of 68 years. 43 patients were diagnosed with higher-risk MDS, 30 had AML and 10- CMML. Median AZA dose was comparable between treated groups. AZA dose reduction was required for 44% of MDS, 17% of AML and 25% of CMML patients. Complete remission (CR) was achieved in 14% of MDS, 7% of AML and 10% of CMML patients. Overall response rate was following: 27% for MDS, 20% for AML and 20% for CMML. Estimated OS at 12 months was 75% for MDS, 60% for AML and 75% for CMML. Median follow-up for MDS/AML/CMML from AZA initiation to last follow-up was 9.0, 9.4 and 9.4 months, respectively. The most common toxicity of AZA therapy was myelosuppression and infections. AZA treatment was effective in a limited number of patients with acceptable safety profile.
C1 [Helbig, Grzegorz] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Chromik, Karolina] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Wozniczka, Krzysztof] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Kopinska, J Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Boral, Kinga] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Dworaczek, Martyna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Koclega, Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Armatys, Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Panz-Klapuch, Marta] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
[Markiewicz, Miroslaw] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Dabrowski street, 25, 40-032 Katowice, Poland.
RP Helbig, G (reprint author), Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, 40-032 Katowice, Poland.
EM ghelbig@o2.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1175
EP 1180
DI 10.1007/s12253-018-00574-0
PG 6
ER
PT J
AU Zheng, J
Xu, T
Feng, Ch
Zhang, Y
AF Zheng, Jing
Xu, Tingting
Feng, Chen
Zhang, Ying
TI MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; miR-195-5p; Overall survival; Prognosis; CIAPIN1
ID Non-small cell lung cancer; miR-195-5p; Overall survival; Prognosis; CIAPIN1
AB Accumulating evidence suggests that microRNAs (miRNAs) has been proven to be a critical regulator in the tumor progression, of which miR-195-5p was reported to function as tumor suppressor in prostate cancer and oral squamous cell carcinoma. However, studies on the clinical significance and biological function of miR-195-5p in non-small cell lung cancer (NSCLC) were still unavailable. Here, we reported that the expression of miR-195-5p was decreased in NSCLC tissues and cell lines. Downregulation of miR-195-5p was significantly associated with TNM stage, tumor size and lymph node metastasis. The Kaplan-Meier survival analysis demonstrated that the survival time of NSCLC patients with high expression of miR-195-5p was longer than those with low expression during the 5-year follow up period (p = 0.0410). COX regression analysis indicated that miR-195-5p expression was an independent prognostic indicator for the survival of NSCLC patients (HR = 2.45, 95% CI: 1.53–4.63; p = 0.007). Results of functional analyses revealed that overexpression of miR-195-5p in A549 cells inhibited cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis using MTT and flow cytometry analysis. Furthermore, bioinformatics and luciferase reporter assays demonstrated that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), an antiapoptotic molecule was a direct target of miR-195-5p in NSCLC cells. Meta-analysis based on Oncomine database showed CIAPIN1 was significantly up-regulated in human lung cancer tissues. Consistently, knockdown of CIAPIN1 phenocopied the inhibitory effects of miR-195-5p overexpression in NSCLC cell function. These findings suggest that miR-195-5p could be used as a potential prognostic predictor and tumor suppressor in NSCLC.
C1 [Zheng, Jing] Taizhou Hospital, Department of Respiratory Medicine, 381 East Zhongshan Road, Jiaojiang District, 318000 Taizhou, Zhejiang, China.
[Xu, Tingting] Taizhou Hospital, Department of Respiratory Medicine, 381 East Zhongshan Road, Jiaojiang District, 318000 Taizhou, Zhejiang, China.
[Feng, Chen] Taizhou Hospital, Department of Respiratory Medicine, 381 East Zhongshan Road, Jiaojiang District, 318000 Taizhou, Zhejiang, China.
[Zhang, Ying] Taizhou Hospital, Department of Respiratory Medicine, 381 East Zhongshan Road, Jiaojiang District, 318000 Taizhou, Zhejiang, China.
RP Xu, T (reprint author), Taizhou Hospital, Department of Respiratory Medicine, 318000 Taizhou, China.
EM Xu_tingting09@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1181
EP 1190
DI 10.1007/s12253-018-0552-z
PG 10
ER
PT J
AU Molnar, Cs
Molnar, S
Bedekovics, J
Mokanszki, A
Gyory, F
Nagy, E
Mehes, G
AF Molnar, Csaba
Molnar, Sarolta
Bedekovics, Judit
Mokanszki, Attila
Gyory, Ferenc
Nagy, Endre
Mehes, Gabor
TI Thyroid Carcinoma Coexisting with Hashimoto’s Thyreoiditis: Clinicopathological and Molecular Characteristics Clue up Pathogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid; Carcinoma; Hashimoto thyreoiditis; Clinicopathology; Molecular pathology
ID Thyroid; Carcinoma; Hashimoto thyreoiditis; Clinicopathology; Molecular pathology
AB Thyroid cancer (TC) coexisting with Hashimoto’s thyroiditis (HT) presents with several characteristic features including multifocality and lower clinical stages compared to de novo carcinomas but its exact biology is still not understood. We reexamined clinico-pathological and molecular correlations between Hashimoto’s thyroditis and papillary thyroid cancer. A total of 262 patients with TC was evaluated who underwent thyroidectomy at the Surgical Department of the University of Debrecen. Clinical data, histology and molecular data were evaluated. Our cohort included 43 patients (16.4%) with (5 male, 38 female) and 219 (83.6%) patients without coexisting HT (48 male, 171 female). Hashimoto’s thyroiditis related thyroid cancer presented predominantly (93.0% of the cases) with the papillary histological type. Multifocality was observed more frequently with coexisting HT (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%)(p = 0.034). In contrast, lymphatic metastasis (pN1) with a significantly reduced frequency in patients with HT (4/11; 36.4%) then without HT (34/41 pN1; 82.9%)(p = 0.002). BRAF V600E mutation could be demonstrated at significantly lower rates in cases of PTC + HT (32.1 vs 60.7%, p < 0.005). High incidence, multifocality and papillary morphology strongly support a causal relation between TC and preexisting Hashimoto’s thyroiditis, the latter to be considered as a preneoplastic condition promoting thyroid carcinogenesis.
C1 [Molnar, Csaba] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4042 Debrecen, Hungary.
[Molnar, Sarolta] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4042 Debrecen, Hungary.
[Bedekovics, Judit] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4042 Debrecen, Hungary.
[Mokanszki, Attila] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4042 Debrecen, Hungary.
[Gyory, Ferenc] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
[Nagy, Endre] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, H-4042 Debrecen, Hungary.
RP Molnar, Cs (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, H-4042 Debrecen, Hungary.
EM molnar.csaba@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1191
EP 1197
DI 10.1007/s12253-019-00580-w
PG 7
ER
PT J
AU Chiang, MR
Kuo, ChW
Wang, WCh
Hou, TCh
Kuo, ChY
Lu, MY
Lai, YCh
AF Chiang, Ming-Ru
Kuo, Chi-Wen
Wang, Wen-Chung
Hou, Tai-Cheng
Kuo, Chen-Yun
Lu, Meng-Yao
Lai, Yen-Chein
TI Correlations between Histological and Array Comparative Genomic Hybridization Characterizations of Wilms Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Wilms tumor; Nephroblastoma; Array comparative genomic hybridization; Molecular pathogenesis
ID Wilms tumor; Nephroblastoma; Array comparative genomic hybridization; Molecular pathogenesis
AB Wilms tumor, or nephroblastoma, is the most common pediatric renal malignancy. Its diagnosis is principally based on histology. Several genetic loci have been shown to be associated with Wilms tumor formation, including WT1, WT2, FWT1, FWT2, CTNNB1, WTX, and TP53. Other loci, such as 1p, 2q, 7p, 9q, 12q, 14q, 16q, 17p, and 22, have also been implicated in the etiology of Wilms tumor. The aim of this study is to elucidate the molecular pathogenesis of this tumor. In the present study, we analyzed the histological appearance and copy number aberrations using array comparative genomic hybridization of six Wilms tumors without somatic mutation in the WT1 gene. Many chromosomal aberrations on array comparative genomic hybridization analysis revealed that the genetics of Wilms tumors are extremely complex. Amplifications and deletions of large DNA fragments were observed in some samples. Amplifications of NDUFV1, ZIC2, SIX1, NR2F2,MIR1469, SOX9, JAG1, MIR6870, and GNAS were found in all six Wilms tumors. Moreover, amplifications of five genes were identified in the Wilms tumors of stromal type and amplifications of at least 10 genes were identified in the Wilms tumors of epithelial type. Our results indicated that amplifications of nine genes are the essential events in the tumorigenesis of Wilms tumor, which may inform its clinical and therapeutic management. In addition, mixed type Wilms tumor may be the heterogeneous group able to be classified using genetic results of epithelial and stromal components based on immunohistochemistry.
C1 [Chiang, Ming-Ru] Jen-Ai Hospital, Department of Pediatrics, 483 Dong Rong Road, 412 Taichung, Taiwan, Republic of China.
[Kuo, Chi-Wen] Jen-Ai Hospital, Department of Pharmacy, 483 Dong Rong Road, 412 Taichung, Taiwan, Republic of China.
[Wang, Wen-Chung] Jen-Ai Hospital, Department of Obstetrics and Gynecology, 483 Dong Rong Road, 412 Taichung, Taiwan, Republic of China.
[Hou, Tai-Cheng] Jen-Ai Hospital, Department of Pathology, 483 Dong Rong Road, 412 Taichung, Taiwan, Republic of China.
[Kuo, Chen-Yun] Jen-Ai Hospital, Department of Pathology, 483 Dong Rong Road, 412 Taichung, Taiwan, Republic of China.
[Lu, Meng-Yao] National Taiwan University Hospital, Department of Pediatrics, 8 Chung-Shan South Road, 100 Taipei, Taiwan, Republic of China.
[Lai, Yen-Chein] Chung Shan Medical University, Department of Medical Laboratory and Biotechnology, No.110, Sec 1, Chien Kuo North Road, 402 Taichung, Taiwan, Republic of China.
RP Lai, YCh (reprint author), Chung Shan Medical University, Department of Medical Laboratory and Biotechnology, 402 Taichung, Taiwan, Republic of China.
EM yenchein@csmu.edu.tw
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1199
EP 1206
DI 10.1007/s12253-019-00601-8
PG 8
ER
PT J
AU Jiang, W
Li, Z
Guo, Q
Wang, H
Ma, M
Sun, J
Chen, Ch
AF Jiang, Wentao
Li, Zhang
Guo, Qingjun
Wang, Honghai
Ma, Ming
Sun, Jisan
Chen, Chiyi
TI Identification of the Pathogenic Biomarkers for Hepatocellular Carcinoma Based on RNA-seq Analyses
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma (HCC); Early diagnosis; RNA-seq
ID Hepatocellular carcinoma (HCC); Early diagnosis; RNA-seq
AB The purpose of this study was to explore potential biomarkers in the diagnosis of hepatocellular carcinoma (HCC) based on RNA-seq. The microarray data GSE98269 were downloaded from the GEO database, including the miRNA, mRNA and lncRNA expression profiles of 3 HCC tissues and 3 normal liver tissues from 3 HCC patients. The limma package was used to identify the differentially expressed miRNAs (DEMs) and the differentially expressed lncRNAs in HCC tissues compared with normal liver tissues. Database of DAVID, KEGG PATHWAY and Reactome were used to perform the functional and pathway enrichment. Putative targets for DEMs, and the miRNA-gene pairs were predicted via the miRWalk V2.0 database. The proteinprotein pairs of DEGs were screened via String software. The expression features of the differentially expressed lncRNAs were analyzed. The regulated network of DEGs and DEMs were constructed, and related genes and miRNAs were detected in the HCC tissues and normal liver samples with Q-PCR. A total of 678 DEGs, 32 DEMs and 411 differential expressed lncRNAs were identified. The DEGs were enriched in 196 GO terms and 79 pathways. 38 negative regulation miRNA-gene pairs and 1205 protein-protein interactions were screened out, and the regulated network was constructed based on them. KNG1, CDK1, EHHADH, CYP3A4, hsa-miR-199a-5p and hsa-miR-455-3p might be biomarkers in the occurrence of HCC.
C1 [Jiang, Wentao] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Li, Zhang] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Guo, Qingjun] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Wang, Honghai] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Ma, Ming] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Sun, Jisan] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
[Chen, Chiyi] Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 24 Fukang Road, Nankai District, 300192 Tianjin, China.
RP Jiang, W (reprint author), Tianjin First Center Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, 300192 Tianjin, China.
EM wentaojiang23@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1207
EP 1213
DI 10.1007/s12253-019-00596-2
PG 7
ER
PT J
AU Samadani, AA
Nikbakhsh, N
Taheri, H
Shafaee, Sh
Fattahi, S
Langroudi, PM
Hajian, K
Akhavan-Niaki, H
AF Samadani, Akbar Ali
Nikbakhsh, Novin
Taheri, Hassan
Shafaee, Shahriyar
Fattahi, Sadegh
Langroudi, Pilehchian Maryam
Hajian, Karimollah
Akhavan-Niaki, Haleh
TI CDX1/2 and KLF5 Expression and Epigenetic Modulation of Sonic Hedgehog Signaling in Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; DNA methylation; Gene expression; Epigenetics
ID Gastric cancer; DNA methylation; Gene expression; Epigenetics
AB Gastric cancer is among the commonplace causes of cancer death worldwide. Sonic hedgehog (Shh) signaling is an important pathway which may be dysregulated in many cancers.CDX1/2, and KLF5are key transcription factors involved in Shh pathway and cancer stem cells. The aim of this study was to investigate the expression and epigenetic alterations of these genes in gastric cancer patients. DNA methylation’s modifications of CDX1, KLF5 and CDX2 genes alongside with the expressions of these genes in gastric cancer tissues and their non-tumoral counterparts (margin tissues) were analyzed using methylation specific sequencing, and Real time PCR Taq man assays, respectively. The expression of CDX1 (P = 0.002) and KLF5 (P = 0.010) were decreased significantly, but it was considerably increased for CDX2 (P = 0.001). Relatively, the results for the regulatory region methylation status of each CpG site had shown a notable fluctuation in these genes with no significant difference in most places. The creation of metastatic lymph nodes in patients was significantly associated with increased expression of CDX2 gene. The modifications of these genes expression can be considered as a cancer biomarker in future studies. Methylation of the investigated genes is not the main mechanism of gastric cancer development.
C1 [Samadani, Akbar Ali] Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research CenterBabol, Iran.
[Nikbakhsh, Novin] Babol University of Medical Sciences, Cancer Research Center, Department of SurgeryBabol, Iran.
[Taheri, Hassan] Babol University of Medical Sciences, Department of GastroenterologyBabol, Iran.
[Shafaee, Shahriyar] Babol University of Medical Sciences, Department of PathologyBabol, Iran.
[Fattahi, Sadegh] Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research CenterBabol, Iran.
[Langroudi, Pilehchian Maryam] Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research CenterBabol, Iran.
[Hajian, Karimollah] Babol University of Medical Sciences, Faculty of Medicine, Department of Social medicine and statisticsBabol, Iran.
[Akhavan-Niaki, Haleh] Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research CenterBabol, Iran.
RP Akhavan-Niaki, H (reprint author), Babol University of Medical Sciences, Health Research Institute, Cellular and Molecular Biology Research Center, Babol, Iran.
EM halehakhavan@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1215
EP 1222
DI 10.1007/s12253-019-00594-4
PG 8
ER
PT J
AU Mohamed, G
Talima, S
Li, L
Wei, W
Rudzki, Z
Allam, MR
Simmons, W
Tao, Q
Murray, GP
AF Mohamed, Ghada
Talima, Soha
Li, Lili
Wei, Wenbin
Rudzki, Zbigniew
Allam, Mahmoud Rasha
Simmons, William
Tao, Qian
Murray, G Paul
TI Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SLIT2; DLBCL; Hypermethylation; Patient survival
ID SLIT2; DLBCL; Hypermethylation; Patient survival
AB SLIT2 has been classified as a major tumour suppressor gene due to its frequent inactivation in different cancer types. However, alterations of SLIT2 expression and relation to patient outcomes in diffuse large B cell lymphoma (DLBCL) remain undefined. The aim of this study was to investigate the expression and the methylation status of SLIT2 gene as well as its relation to patient outcomes in DLBCL. Immunohistochemical (IHC) staining was carried out to detect the expression of SLIT2 in a series of 108 DLBCL cases. Re-analysis of previously published dataset (GSE10846) that measured gene expression in DLBCL patients who had received CHOP or R-CHOP therapy was performed to identify associations between SLIT2 and patients survival. Laser capture microdissection was performed to isolate GC B cells and DLBCL primary tumor cells. Bisulfite treatment and methylation-specific PCR (MSP) analysis were done to assess SLIT2 promotor methylation status.We report that the expression of SLIT2 protein was reduced in a subset of DLBCL cases and this was significantly correlated with advanced clinical stage (p = 0.041) and was an independent predictor of worse overall survival (OS) (p = 0.012). Re-analysis of published gene expression data showed that reduced SLIT2 mRNA expression was significantly correlated with worse OS in R-CHOP-treated ABC DLBCL patients (p = <0.01). Hypermethylation of the SLIT2 promotor was significantly correlated with low SLIT2 expression (p = 0.009). Our results provide a novel evidence of reduced expression of SLIT2 that is associated with promoter hypermethylation and adverse outcomes in patients with DLBCL.
C1 [Mohamed, Ghada] Cairo University, National Cancer Institute, Department of PathologyGiza, Egypt.
[Talima, Soha] Cairo University, Faculty of Medicine, Clinical Oncology DepartmentGiza, Egypt.
[Li, Lili] The Chinese University of Hong Kong, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health SciencesHong Kong, Hong Kong.
[Wei, Wenbin] University of Birmingham, Institute of Cancer and Genomic Sciences, Vincent Drive, Edgbaston, B15 2TT Birmingham, UK.
[Rudzki, Zbigniew] University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Department of Cellular PathologyBirmingham, UK.
[Allam, Mahmoud Rasha] Cairo University, National Cancer Institute, Biostatistic and Cancer Epidemiology DepartmentGiza, Egypt.
[Simmons, William] University of Birmingham, Institute of Cancer and Genomic Sciences, Vincent Drive, Edgbaston, B15 2TT Birmingham, UK.
[Tao, Qian] The Chinese University of Hong Kong, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health SciencesHong Kong, Hong Kong.
[Murray, G Paul] University of Birmingham, Institute of Cancer and Genomic Sciences, Vincent Drive, Edgbaston, B15 2TT Birmingham, UK.
RP Mohamed, G (reprint author), Cairo University, National Cancer Institute, Department of Pathology, Giza, Egypt.
EM dr.ghada.elshafaee@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1223
EP 1231
DI 10.1007/s12253-019-00600-9
PG 9
ER
PT J
AU Martin-Manzo, VM
Lara, C
Vargas-de-Leon, C
Carrero, J
Queipo, G
Fonseca-Sanchez, M
Mejia-Dominguez, RN
Kershenobich, D
Mummidi, S
Zentella-Dehesa, A
Hernandez, J
AF Martin-Manzo, Victoria Miriam
Lara, Carlos
Vargas-de-Leon, Cruz
Carrero, Julio
Queipo, Gloria
Fonseca-Sanchez, Miguel
Mejia-Dominguez, R Nancy
Kershenobich, David
Mummidi, Srinivas
Zentella-Dehesa, Alejandro
Hernandez, Joselin
TI Interaction of Breast Cancer and Insulin Resistance on PD1 and TIM3 Expression in Peripheral Blood CD8 T Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Insulin resistance; TIM3; PD1
ID Breast cancer; Insulin resistance; TIM3; PD1
AB Epidemiological evidence points to a link between insulin resistance (IR) and breast cancer (BrCA). Insulin plays a role in CD8+ Tcells (CD8T) differentiation and function and affects adipocytokines levels. CD8Tactivity in BrCA is associated with favorable outcome; while PD1 and TIM3 are markers of CD8T exhaustion and play critical roles in the negative regulation of T cell responses. Patients with (BrCA) have high expression levels of PD1 on circulating. Therefore, we hypothesized that BrCA and IR could affect PD1 and/or TIM3 expression on circulating CD8T. We determine PD1 and TIM3 expression on CD8T and analyze the relationship of CD8T phenotype with serum insulin and plasma adipocytokines levels in the different groups. We enrolled four groups of treatment-naive patients: women without neoplasms (Neo-)/without IR (IR-), Neo−/with IR (IR+), BrCa/ IR- and BrCa/IR+.We found interactions between BrCA and IR with respect to TIM3 on naive and central memory (CM) CD8T subsets. Furthermore, BrCA had a greater PD1 + TIM3- CD8T frequency in CD8T subsets than Neo-. IR+ presented a significantly lower PD1 + TIM3- frequency in CD8Tsubsets compare to Non-IR. In addition, we found a negative correlation between insulin levels, HOMA and frequency of PD1 + TIM3- in CD8T and a positive correlation between adiponectin levels and the frequency PD1 + TIM3- in CD8T. The increased expression of PD1 on different subsets of CD8T from BrCa patients is consistent with immunological tolerance, whereas IR has a contrary effect. IR could have a deleterious role in the activation of CD8T that can be relevant to new BrCa immunotherapy.
C1 [Martin-Manzo, Victoria Miriam] Universidad Nacional Autonoma de Mexico, Programa de Doctorado en Ciencias BiomedicasMexico City, Mexico.
[Lara, Carlos] Hospital General de Mexico Dr. Eduardo Liceaga, Servicio de OncologiaMexico City, Mexico.
[Vargas-de-Leon, Cruz] Instituto Politecnico Nacional, Escuela Superior de MedicinaMexico City, Mexico.
[Carrero, Julio] Universidad Nacional Autonoma de Mexico, Instituto de Investigaciones Biomedicas, Departamento de InmunologiaMexico City, Mexico.
[Queipo, Gloria] Hospital General de Mexico Dr. Eduardo Liceaga, Departamento de GeneticaMexico City, Mexico.
[Fonseca-Sanchez, Miguel] Hospital General de Mexico Dr. Eduardo Liceaga, Departamento de GeneticaMexico City, Mexico.
[Mejia-Dominguez, R Nancy] CIC-Universidad Nacional Autonoma de Mexico, Red de Apoyo a la Investigacion (RAI)Mexico City, Mexico.
[Kershenobich, David] Universidad Nacional Autonoma de Mexico, Facultad de Medicina, HIPAM, Unidad de Investigacion en Medicina ExperimentalMexico City, Mexico.
[Mummidi, Srinivas] University of Texas Rio Grande Valley, South Texas Diabetes and Obesity InstituteEdinburg, TX, USA.
[Zentella-Dehesa, Alejandro] Universidad Nacional Autonoma de Mexico, Departamento de Bioquimica INCMNSZ; Centro de Cancer, CM ABMexico City, Mexico.
[Hernandez, Joselin] Universidad Nacional Autonoma de Mexico, Facultad de Medicina, HIPAM, Unidad de Investigacion en Medicina ExperimentalMexico City, Mexico.
RP Hernandez, J (reprint author), Universidad Nacional Autonoma de Mexico, Facultad de Medicina, HIPAM, Unidad de Investigacion en Medicina Experimental, Mexico City, Mexico.
EM joselin.hernandezruiz@utrgv.edu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1233
EP 1243
DI 10.1007/s12253-019-00610-7
PG 11
ER
PT J
AU Zhao, W
Chen, Sh
Hou, X
Liao, Q
Chen, G
Zhao, Y
AF Zhao, Wenjing
Chen, Shaobo
Hou, Xianming
Liao, Quan
Chen, Ge
Zhao, Yupei
TI Predictive Factors of Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid microcarcinoma; Lateral lymph node metastasis; Skip metastasis; Predictors
ID Papillary thyroid microcarcinoma; Lateral lymph node metastasis; Skip metastasis; Predictors
AB This study was designed to determine the incidence and predictive factors for lateral lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC). From January 2014 to July 2015, a retrospective review was conducted of 215 patients with PTMC who underwent total thyroidectomy and central lymph node dissection (LND) with lateral LND. Correlations of lateral LNM with clinicopathological features were examined using univariate analyses. Risk factors for lateral LNM were identified by multivariate analysis. Lateral LNM was observed in 163(75.8%) cases of 215 patients and often involved in level III (82.2%) and level IV (65.6%), with most found in two-levels (41.1%) and single-level (33.7%) models. Multivariate analyses showed that central LNM(odds ratio [OR]: 8.28, 95%confidence interval [CI]: 3.43–19.98, p < 0.001) and upper portion location (OR: 2.87 [CI: 1.34–6.09]; p = 0.007) were independent predictive factors for lateral LNM. The incidence of skip metastasis-Lateral LNM with central Lymph nodes negative-was 8.6% (14/163). Age ≥ 45 years old (OR: 4.37 [CI: 1.14– 16.66]; p = 0.031) and upper portion location (OR: 4.34 [CI: 1.27–14.78]; p = 0.019) were independent risk factors for skip metastasis by multivariate analyses. Taken together, patients with PTMC with central LNM and tumor in the upper pole were more likely to present with lateral LNM. Even if there was no central LNM, patients with an age ≥ 45 years old and tumors in the upper portion of the thyroid should be evaluated carefully for possible lateral LNM.
C1 [Zhao, Wenjing] Chinese Academy of Medical Science & Peking Union Medical College, Peking Union Medical College Hospital, Central Laboratory, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
[Chen, Shaobo] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
[Hou, Xianming] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
[Liao, Quan] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
[Chen, Ge] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
[Zhao, Yupei] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 1 Shuai Fu Yuan Hu Tong, 100730 Beijing, China.
RP Chen, G (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, 100730 Beijing, China.
EM pumchchenge@163.com
CR Yu XM, Wan Y, Sippel RS, Chen H, 2011, Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Ann Surg 254:653–660
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Chung YS, Kim JY, Bae JS et al, 2009, Lateral lymph node metastasis in papillary thyroid carcinoma: results of therapeutic lymph node dissection. Thyroid 19:241–245
Verburg FA, Mader U, Tanase K et al, 2013, Life expectancy is reduced in differentiated thyroid cancer patients≥45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients. J Clin Endocrinol Metab 98:172–180
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1245
EP 1251
DI 10.1007/s12253-018-0511-8
PG 7
ER
PT J
AU Khemka, R
Gupta, M
Jena, KN
AF Khemka, Rashi
Gupta, Monica
Jena, Kanta Nehar
TI CML with Megakaryocytic Blast Crisis: Report of 3 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chronic Myeloid Leukemia; Megakaryocytic blast crisis; Flowcytometric immunophenotyping
ID Chronic Myeloid Leukemia; Megakaryocytic blast crisis; Flowcytometric immunophenotyping
AB Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm consistently associated with the BCR-ABL1 fusion gene located in the Philadelphia chromosome. The Blast Phase is diagnosed when blasts are ≥20% of the peripheral blood white cell count or of bone marrow nucleated cells or when there is an extramedullary blast proliferation. Megakaryocytic blast crisis as the presenting manifestation of CML is extremely rare and only 7 reported cases were found in the literature. Out of 34 cases of CML-Blast Phase between April 2015 and June 2016, 3 cases showed megakaryocytic differentiation. 2 of these presented in Blast phase as the first manifestation of CML and the third case was a known case of CML-Chronic phase. Flow cytometric immunophenotyping was performed on peripheral blood/bone marrow using 6- color flow cytometer Navios. On CD45 vs SSC two distinct populations of blasts were seen in two cases and single population in the third case. All the 3 cases were positive for CD61, cCD41, cCD61 confirming the megakaryocytic lineage. The clinical features, morphologic and cytogenetic findings help in the identification and distinction of megakaryocytic blast phase of CML from Acute Megakayoblastic Leukemia. The diagnosis of such rare presentation of CML is essential for determining the choice of treatment. Therefore including a megakaryocytic marker in the primary flow cytometry panel is important so that these cases are not underdiagnosed as Acute myeloid leukemia because of expression of CD13 and CD33 only.
C1 [Khemka, Rashi] Delhi State Cancer Institute, Department of Oncopathology, Dilshad Garden, 110095 Delhi, India.
[Gupta, Monica] Delhi State Cancer Institute, Department of Oncopathology, Dilshad Garden, 110095 Delhi, India.
[Jena, Kanta Nehar] Delhi State Cancer Institute, Department of Clinical Oncology, Dilshad Garden, 110095 Delhi, India.
RP Gupta, M (reprint author), Delhi State Cancer Institute, Department of Oncopathology, 110095 Delhi, India.
EM drmonica123@gmail.com
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Campiotti L, GrandiAM, BiottiMG, Ultori C, Solbiati F, Codari R, Venco A, 2007, Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. Am J Hematol 82:231–233
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Al-Shehri A, Al-Seraihy A, Owaidah TM, Belgaumi AF, 2010, Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia. Hematol Oncol Stem Cell Ther 3(1):42–46
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Morris EL, Dutcher JP, 2005, Blastic phase of chronic myelogenous leukemia. Clin Adv Hematol Oncol 3:547–552
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1253
EP 1258
DI 10.1007/s12253-018-0484-7
PG 6
ER
PT J
AU da Rocha Boeira, Th
Wolf, MJ
Coser, J
Grivicich, I
Simon, D
Lunge, RV
AF da Rocha Boeira, Thais
Wolf, Michel Jonas
Coser, Janaina
Grivicich, Ivana
Simon, Daniel
Lunge, Ricardo Vagner
TI Polymorphisms in Genes Related to Cervical Cancer in A Brazilian Population: A Case-Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [da Rocha Boeira, Thais] Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a SaudeCanoas, RS, Brazil.
[Wolf, Michel Jonas] Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a SaudeCanoas, RS, Brazil.
[Coser, Janaina] Universidade de Cruz Alta / Universidade Regional do Noroeste do Estado do Rio Grande do Sul (UNICRUZ/UNIJUÍ), Programa de Pos-Graduacao em Atencao Integral a SaudeCruz Alta / Ijui, RS, Brazil.
[Grivicich, Ivana] Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a SaudeCanoas, RS, Brazil.
[Simon, Daniel] Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a SaudeCanoas, RS, Brazil.
[Lunge, Ricardo Vagner] Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a SaudeCanoas, RS, Brazil.
RP Wolf, MJ (reprint author), Universidade Luterana do Brasil, PPG Biologia Celular e Molecular Aplicada a Saude, Canoas, Brazil.
EM jonasmwolf@gmail.com
CR IARC, International Agency for Research on Cancer. Pharmaceuticals: a review of human carcinogens. Lyon, 2012., IARC monographs on the evaluation of carcinogenic risks to humans, v. 100E)
Magnusson PK, Sparen P, Gyllensten UB, 1999). Genetic link to cervical tumours. Nature. 1;400(6739):29–30
Wang SS, BrattiMC, Rodriguez AC, Herrero R, Burk RD, Porras C, Gonzalez P, Sherman ME, Wacholder S, Lan ZE, Schiffman M, Chanock SJ, Hildesheim A, 2009, Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer. J Infect Dis 199(1):20–30
Wang SS, Gonzalez P, Yu K, Porras C, Li Q, SafaeianM, Rodriguez AC, Sherman ME, Bratti C, Schiffman M, Wacholder S, Burk RD, Herrero R, Chanock SJ, Hildesheim A, 2010, Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS One 5(1):e8667
Coser J, Boeira Tda R, Wolf JM et al, 2016, Cervical human papillomavirus infection and persistence: a clinic-based study in the countryside from South Brazil. Braz J Infect Dis 20(1):61–68
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1259
EP 1261
DI 10.1007/s12253-018-0414-8
PG 3
ER
PT J
AU Mandal, P
AF Mandal, Paramita
TI Recent advances of Blood telomere length (BTL) shortening: A potential biomarker for development of cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Telomere length; Shortening; Cancer; Cisease; Biomarker
ID Telomere length; Shortening; Cancer; Cisease; Biomarker
AB Telomeres, the specific DNA–protein structures remains at both ends of each chromosome and are crucial in the maintenance of chromosome integrity and genomic stability with protection of the chromosome from damage and degradation.. Increasing evidences suggest the correlation between telomere length and the development of cancers, but the findings remain obscure. Generally, the average length of telomere repeats at the ends of chromosomes that gives a clue in providing indirect information about their mitotic history. It plays immense role in preventing genome from nucleolytic degradation, unnecessary recombination, repair, and interchromosomal fusion. It has major role in storing the information in the genome. Telomere attrition during successive cell divisions induces chromosomal instability and contributes significantly to genomic rearrangements that can result in tumorigenesis. Convincing evidence documented that a meagre portion of telomeric DNA is expelled out during mitotic stage of cell division. But accelerated shortening telomere length at critical level triggers senescence and/or apoptosis. Various harmful agents with bad lifestyles are responsible in inducing shortening of telomere length with damage of DNA resulting to occurrence of disease with shortening of lifespan. Besides, telomerases, the specialized polymerase that synthesizes new telomere repeats and is strongly associated with cancer facilitating malignant transformation. Therefore, in the study, it is highlighted that the telomeres may play diverse roles in different cancers whereas shortening of telomere length may be risk factors for the development of tumors.
C1 [Mandal, Paramita] The University of Burdwan, Department of ZoologyBurdwan, West Bengal, India.
RP Mandal, P (reprint author), The University of Burdwan, Department of Zoology, Burdwan, India.
EM paramita.mandal2@gmail.com
CR Hirashima K, Migita T, Sato S, MuramatsuY, Ishikawa Y, Seimiyaa H, 2013, Telomere Length Influences Cancer Cell Differentiation In Vivo. Molecular and Cellular Biology 33(15):2988–2995
Leteurtre F, Li X, Guardiola P, Le Roux G, Sergere J-C, Richard P, Carosella ED, Gluckman E, 1999, Accelerated telomere shortening and telomerase activation in Fanconi’s anaemia. Br J Haematol 105(4):883–893
Willeit P, Willeit J, Mayr A, Oberhollenzer F, Brandstatter A, Kronenberg F, Kiechl S, 2010, 2010. Telomere Length and Risk of Incident Cancer and Cancer Mortality JAMA 304(1):69–75
Jafri MA, Ansari SA, Alqahtani MH, Shay JW, 2016, Roles of telomeres and telomerase in cancer, and advances in telomerasetargeted therapies. Genome Medicine 8:69
Moon IK, Jarstfer MB, 2007, The human telomere and its relationship to human disease, therapy, and tissue engineering. Frontiers in Bioscience 12(8-12):4595
Zhu X, Han W, Xue W, Zou Y, Xie C, Du J, Jin G, 2016, The association between telomere length and cancer risk in population studies. Scientific Reports 6(1)
Shay JW, 2013, Are Short Telomeres Predictive of Advanced Cancer? Cancer Discovery 3(10):1096–1098
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Nasir NF, Kannan TP, Sulaiman SA, Shamsuddin S, Azlina A, Stangaciu S, 2015, The relationship between telomere length and beekeeping among Malaysians. AGE 37(3)
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Van Steensel B, Smogorzewska A, de Lange T, 1998, TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–413
Stewart JA, Chaiken MF, Wang F, Price CM, 2012, Maintaining the end: roles of telomere proteins in end-protection, telomere replication and length regulation. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 730(1):12–19
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Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, Svenson U, Goran R, Dean Hosgood H, Shen M, Wei Q, Toland AE, 2011, Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis. PLoS ONE 6(6):e20466
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Cottliar AS, Slavutsky IR, 2001, Telomeres and telomerase activity: their role in aging and in neoplastic development. Medicina, B Aires). 61(3):335–342
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1263
EP 1265
DI 10.1007/s12253-018-0425-5
PG 3
ER
PT J
AU Sarode, SG
Sarode, CS
Gadbail, RA
Gondivkar, Sh
Patil, Sh
AF Sarode, S Gargi
Sarode, C Sachin
Gadbail, R Amol
Gondivkar, Shailesh
Patil, Shankargouda
TI Tumor Associated Tissue Eosinophilia in Ameloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Sarode, S Gargi] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, Sant-Tukaram nagar, Pimpri, 411018 Pune, Maharashtra, India.
[Sarode, C Sachin] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, Sant-Tukaram nagar, Pimpri, 411018 Pune, Maharashtra, India.
[Gadbail, R Amol] Indira Gandhi Government Medical College and Hospital, Department of DentistryNagpur, Maharashtra, India.
[Gondivkar, Shailesh] Government Dental College & Hospital, Department of Oral Medicine and RadiologyNagpur, Maharashtra, India.
[Patil, Shankargouda] Jazan University, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral PathologyJazan, Saudi Arabia.
RP Sarode, CS (reprint author), Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, 411018 Pune, India.
EM drsachinsarode@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2019
VL 25
IS 3
BP 1267
EP 1268
DI 10.1007/s12253-018-0499-0
PG 2
ER
PT J
AU Fucic, A
Aghajanyan, A
Culig, Z
Le Novere, N
AF Fucic, Aleksandra
Aghajanyan, Anna
Culig, Zoran
Le Novere, Nicolas
TI Systems Oncology: Bridging Pancreatic and Castrate Resistant Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Pancreatic cancer; Castrate resistant prostate cancer; Cancer marker; Systems oncology; Cancer profiling
ID Pancreatic cancer; Castrate resistant prostate cancer; Cancer marker; Systems oncology; Cancer profiling
AB Large investments by pharmaceutical companies in the development of new antineoplastic drugs have not been resulting in adequate advances of new therapies. Despite the introduction of new methods, technologies, translational medicine and bioinformatics, the usage of collected knowledge is unsatisfactory. In this paper, using examples of pancreatic ductal adenocarcinoma (PaC) and castrate-resistant prostate cancer (CRPC), we proposed a concept showing that, in order to improve applicability of current knowledge in oncology, the re-clustering of clinical and scientific data is crucial. Such an approach, based on systems oncology, would include bridging of data on biomarkers and pathways between different cancer types. Proposed concept would introduce a new matrix, which enables combining of already approved therapies between cancer types. Paper provides a (a) detailed analysis of similarities in mechanisms of etiology and progression between PaC and CRPC, (b) diabetes as common hallmark of both cancer types and (c) knowledge gaps and directions of future investigations. Proposed horizontal and vertical matrix in cancer profiling has potency to improve current antineoplastic therapy efficacy. Systems biology map using Systems Biology Graphical Notation Language is used for summarizing complex interactions and similarities of mechanisms in biology of PaC and CRPC.
C1 [Fucic, Aleksandra] Institute for Medical Research and Occupational Health, Ksaverska c 2, 10000 Zagreb, Croatia.
[Aghajanyan, Anna] Peoples’ Friendship University of Russia, Institute of MedicineMoscow, Russian Federation.
[Culig, Zoran] Medical University of Innsbruck, Department of UrologyInnsbruck, Austria.
[Le Novere, Nicolas] Babraham InstituteCambridge, UK.
RP Fucic, A (reprint author), Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia.
EM afucic@imi.hr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1269
EP 1277
DI 10.1007/s12253-018-0467-8
PG 9
ER
PT J
AU Popiel, A
Kobierzycki, Ch
Dziegiel, P
AF Popiel, Aneta
Kobierzycki, Christopher
Dziegiel, Piotr
TI The Role of Testin in Human Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Testin; Cancerogenesis; Breast cancer; Ovarian cancer; Gastrointestinal cancers
ID Testin; Cancerogenesis; Breast cancer; Ovarian cancer; Gastrointestinal cancers
AB Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1–9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.
C1 [Popiel, Aneta] Wroclaw Medical University, Department of Human Morphology and EmbryologyWroclaw, Poland.
[Kobierzycki, Christopher] Wroclaw Medical University, Department of Human Morphology and EmbryologyWroclaw, Poland.
[Dziegiel, Piotr] Wroclaw Medical University, Department of Human Morphology and EmbryologyWroclaw, Poland.
RP Popiel, A (reprint author), Wroclaw Medical University, Department of Human Morphology and Embryology, Wroclaw, Poland.
EM aneta.popiel@live.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1279
EP 1284
DI 10.1007/s12253-018-0488-3
PG 6
ER
PT J
AU Koohini, Z
Koohini, Z
Teimourian, Sh
AF Koohini, Zahra
Koohini, Zohreh
Teimourian, Shahram
TI Slit/Robo Signaling Pathway in Cancer; a New Stand Point for Cancer Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Slite; Robo; Tumor angiogenesis; Tumor markers
ID Slite; Robo; Tumor angiogenesis; Tumor markers
AB Angiogenesis and metastasis are two critical steps for cancer cells survival and migration. The microenvironment of tumor sphere induces new blood vessels formation for enhancing tumor mass. Preexisting capillaries and postcapillary venules in tumors bring about new blood vessels. ROBO1-ROBO4 are transmembrane receptors family which act as guidance molecules of the nervous system. The SLITs family is secreted glycoproteins that bind to these receptors. SLIT-ROBO signaling pathway plays an important role in neurogenesis and immune response. Linkage between ROBOs and their ligands (SLITs) induce chemorepllent signal for regulation of axon guidance and leukocyte cell migration, recent finding shows that it is also involved in endothelial cell migration and angiogenesis in various type of cancers. In this article we review recent finding of SLIT-ROBO pathway in angiogenesis and metastasis.
C1 [Koohini, Zahra] Iran University of Medical Sciences, School of Medicine, Department of Medical GeneticsTehran, Iran.
[Koohini, Zohreh] Mazandaran University of Medical Sciences, School of Medicine, Department of ImmunologySari, Iran.
[Teimourian, Shahram] Iran University of Medical Sciences, School of Medicine, Department of Medical GeneticsTehran, Iran.
RP Teimourian, Sh (reprint author), Iran University of Medical Sciences, School of Medicine, Department of Medical Genetics, Tehran, Iran.
EM teimourian.sh@iums.ac.ir
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1285
EP 1293
DI 10.1007/s12253-018-00568-y
PG 9
ER
PT J
AU Ying, J
Qiu, X
Yu, L
Zhang, M
AF Ying, Jie
Qiu, Xiaoyan
Yu, Lu
Zhang, Miaomiao
TI SOCS1 and its Potential Clinical Role in Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE SOCS1; Cell signaling; Ubiquitination; Tumors
ID SOCS1; Cell signaling; Ubiquitination; Tumors
AB Suppressor of cytokine signaling1 (SOCS1), as a member of SOCS family, has been widely studied in recent years. It has been found that SOCS1 not only participates in cell signaling, but also in ubiquitination mediated protein degradation process. Both of these two functions play an important role in the growth and proliferation of cells. Therefore, researchers speculated that SOCS1 also played an important role in tumors. This review mainly focuses on the structure, transcriptional regulation and functions of SOCS1 protein, and finally describes the possible clinical role of SOCS1 protein in tumors.
C1 [Ying, Jie] Xuyi People’s Hospital, Department of Clinical Research Center, 211700 Xuyi, Jiangsu, China.
[Qiu, Xiaoyan] Xuyi People’s Hospital, Department of Clinical Research Center, 211700 Xuyi, Jiangsu, China.
[Yu, Lu] Xuyi People’s Hospital, Department of Clinical Research Center, 211700 Xuyi, Jiangsu, China.
[Zhang, Miaomiao] Xuyi People’s Hospital, Department of Clinical Research Center, 211700 Xuyi, Jiangsu, China.
RP Zhang, M (reprint author), Xuyi People’s Hospital, Department of Clinical Research Center, 211700 Xuyi, China.
EM caotiantian198709@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1295
EP 1301
DI 10.1007/s12253-019-00612-5
PG 7
ER
PT J
AU Liu, H
Yin, Q
Yang, G
Qie, P
AF Liu, Huining
Yin, Qifan
Yang, Guang
Qie, Peng
TI Prognostic Impact of Tumor Spread Through Air Spaces in Non-small Cell Lung Cancers: a Meta-Analysis Including 3564 Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Spread through air spaces; Non-small cell lung cancer; Prognosis; Meta-analysis
ID Spread through air spaces; Non-small cell lung cancer; Prognosis; Meta-analysis
AB Surgical resection is the most effective treatment for early stage lung adenocarcinoma. However, the rate of 5-year postoperative recurrence reaches 30%, Spread Through Air Spaces(STAS) is a recently described novel invasive pattern of lung cancer, According to the 2015 WHO classification. STAS is defined as micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor, However, the prognostic role of STAS in lung cancer is not known, The aim of the current study is to evaluate the association between STAS and clinical outcome of lung cancer patients after surgical resection through ameta-analysis. Systematic research was conducted using three online databases to search for studies published before August 1, 2018. The 5-year RFS and OS for non-small cell lung cancer patients after surgical resection with or without STAS were compared. The studies were selected according to rigorous inclusion and exclusion criteria. Meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effective measures. Included in our meta-analysis were 12 studies, published from 2015 to 2018, with a total of 3564 patients. Our results clearly depicted that the presence of STAS predicted a worse outcome for 5-year RFS with the combined HR of 1.84(95% CI: 1.59–2.12). Meta-analysis of these 8 studies showed that patients with the presence of STAS were associated with shorter 5-year OS (the pooled HR:1.78, 95% CI: 1.51– 2.11). This meta-analysis illuminated that the presence of STAS might be a unfavorable prognostic factor for patients with NSCLC. it should be paid sufficient attention and recorded in pathologic reports, which can indicate treatment choice and prognosis of patients. In future, more studies with well-designed and large-scale are needed to confirm the conclusion.
C1 [Liu, Huining] Hebei Provincal General Hospital, Department of Thoracic Surgery, 348,West He-Ping Road, 050051 Shijiazhuang, Hebei Province, China.
[Yin, Qifan] Hebei Provincal General Hospital, Department of Thoracic Surgery, 348,West He-Ping Road, 050051 Shijiazhuang, Hebei Province, China.
[Yang, Guang] Hebei Provincal General Hospital, Department of Thoracic Surgery, 348,West He-Ping Road, 050051 Shijiazhuang, Hebei Province, China.
[Qie, Peng] Hebei Provincal General Hospital, Department of Thoracic Surgery, 348,West He-Ping Road, 050051 Shijiazhuang, Hebei Province, China.
RP Liu, H (reprint author), Hebei Provincal General Hospital, Department of Thoracic Surgery, 050051 Shijiazhuang, China.
EM liuhuining1972@163.com
CR Brundage MD, Davies D, Mackillop WJ, 2002, Prognostic factors in non-small cell lung cancer: a decade of progress. Chest 122(3): 1037–1057
Siegel RL, Miller KD, Jemal A, 2015, Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29
Mino-Kenudson M, Mark EJ, 2011, Reflex testing for epidermal growth factor receptor mutation and anaplastic lymphoma kinase fluoresce nce in situ hybridization in non-small cell lung cancer. Arch Pathol Lab Med 135(5):655–664
Hung J-J, Jeng W-J, Hsu W-H, Chou T-Y, Huang B-S, Wu Y-C, 2012, Predictors of death, local recurrence, and distant metastasis in completely resected pathological stage-I non–small-cell lung Cancer. J Thorac Oncol 7(7):1115–1123
Shiono S, Yanagawa N, 2016, Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. Interact Cardiovasc Thorac Surg 23(4):567–572
Kadota K, Nitadori J-I, Sima CS et al, 2015, Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage I lung adenocarcinomas. J Thorac Oncol 10(5):806–814
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Lu S, Tan KS, Kadota K, Eguchi T, Bains S, Rekhtman N, Adusumilli PS, Travis WD, 2017, Spread through air spaces, STAS, is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol 12(2):223–234
Eguchi T, Kameda K, Lu S et al, 2017, OA07.06 in early-stage lung adenocarcinomas, survival by tumor size, T, is further stratified by tumor spread through air spaces. J Thorac Oncol 12(1, Supplement):S270-S1
Lu S, Eguchi T, Tan KS, Bains S, Kadota K, Rekhtman N, Adusumilli P, Travis W, 2017, Tumor spread through air spaces, STAS, in lung squamous cell cancer is an independent risk factor: a competing risk analysis. J Thorac Oncol 12(1): S412–S4S3
Yanagawa N, Shiono S, Abiko M, Suzuki K, Yarimizu K, 2017, The clinical impact of spread through air spaces, STAS, in surgically resected pStage I lung squamous cell carcinoma. J Thorac Oncol 12(1):S1119–S1S20
Yanagawa N, Shiono S, Endo M, Ogata SY, 2018, Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage I lung squamous cell carcinoma, but not in stage II and III. Lung Cancer, Amsterdam, Netherlands, 120:14–21
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1303
EP 1310
DI 10.1007/s12253-019-00616-1
PG 8
ER
PT J
AU Smolarz, B
Brys, M
Forma, E
Zadrozny, M
Bienkiewicz, J
Romanowicz, H
AF Smolarz, Beata
Brys, Magdalena
Forma, Ewa
Zadrozny, Marek
Bienkiewicz, Jan
Romanowicz, Hanna
TI Data on Single Nucleotide Polymorphism of DNA Repair Genes and Breast Cancer Risk from Poland
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA repair; Single nucleotide polymorphism; Breast cancer
ID DNA repair; Single nucleotide polymorphism; Breast cancer
AB Single nucleotide polymorphisms (SNPs) may modify the risk of cancer. They may be then regarded as potential markers of carcinogenesis. The aim of this study was to analyze the frequency of genotypes and alleles of SNPs in DNA repair genes and to investigate the influence this genetic variation exerts on breast cancer in Polish females. The test group comprised 600 females with breast cancer and 600 healthy controls. Genomic DNA was isolated and the SNPs in DNA repair genes were determined by High-Resolution Melter (HRM) technique. Following polymorphisms were analysed: Arg399Gln (rs25487) of the XRCC1, Gly322Asp (rs4987188) of the hMSH2, Lys751Gln (rs13181) of the XPD, Arg188His (rs3218536) of the XRCC2, P871L (rs799917) of the BRCA1 and N372H (rs144848) of the BRCA2 gene. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele. Statistically significant correlations were identified between 4 single nucleotide polymorphisms and the breast cancer risk: rs25487 rs4987188 rs13181 and rs799917. The alleles XRCC1-Gln (OR 5.11; 95% CI 5.68–11.64, p < .0001), hMSH2-Asp (OR 4.66; 95% CI 3.90–5.56, p < .0001), XPD-Gln (OR 2.65; 95% CI 2.24–3.14, p < .0001) and BRCA1-L (OR 1.45; 95% CI 1.24–1.71, p < .0001) genes were strongly correlated with this malignancy. No correlation was found between the studied SNPs and tumor grading nor the lymph node status. Further research on larger groups is warranted to determine the influence of above-mentioned genetic variants on breast cancer risk.
C1 [Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Brys, Magdalena] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-237 Lodz, Poland.
[Forma, Ewa] Medical University of Lodz, Department of Chemistry and Clinical Biochemistry, Pomorska 141/143, 90-237 Lodz, Poland.
[Zadrozny, Marek] Polish Mother’s Memorial Hospital - Research Institute, Department of Oncological Surgery and Breast Diseases, Rzgowska 281/289, 93-338 Lodz, Poland.
[Bienkiewicz, Jan] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Rzgowska 281/289, 93-338 Lodz, Poland.
[Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
RP Smolarz, B (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, 93-338 Lodz, Poland.
EM smolbea@wp.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1311
EP 1317
DI 10.1007/s12253-017-0370-8
PG 7
ER
PT J
AU Schneider, B
Riedel, K
Zhivov, A
Huehns, M
Zettl, H
Guthoff, FR
Junemann, A
Erbersdobler, A
Zimpfer, A
AF Schneider, Bjoern
Riedel, Katrin
Zhivov, Andrey
Huehns, Maja
Zettl, Heike
Guthoff, F Rudolf
Junemann, Anselm
Erbersdobler, Andreas
Zimpfer, Annette
TI Frequent and Yet Unreported GNAQ and GNA11 Mutations are Found in Uveal Melanomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uveal melanoma; GNAQ/GNA11 mutation; Driver mutation frequency; Survival
ID Uveal melanoma; GNAQ/GNA11 mutation; Driver mutation frequency; Survival
AB Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing.A total of 64.4GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations. Overall survival was significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In concordance with previous studies, high frequencies of mutations in GNAQ or GNA11 were detected. Interestingly, in about 20% of UM, not yet reported mutations in GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation analysis in routine diagnostic procedures might be helpful for future therapeutic decisions.
C1 [Schneider, Bjoern] University Medicine Rostock, Institute of Pathology, Strempelstraße 14, 18055 Rostock, Germany.
[Riedel, Katrin] University Medicine Rostock, Department of OphthalmologyRostock, Germany.
[Zhivov, Andrey] OSG MVZ Betriebs GmbH, Ophtalmology, OMS, AnestheticsBamberg, Germany.
[Huehns, Maja] University Medicine Rostock, Institute of Pathology, Strempelstraße 14, 18055 Rostock, Germany.
[Zettl, Heike] University Medicine Rostock, Clinical Cancer RegistryRostock, Germany.
[Guthoff, F Rudolf] University Medicine Rostock, Department of OphthalmologyRostock, Germany.
[Junemann, Anselm] University Medicine Rostock, Department of OphthalmologyRostock, Germany.
[Erbersdobler, Andreas] University Medicine Rostock, Institute of Pathology, Strempelstraße 14, 18055 Rostock, Germany.
[Zimpfer, Annette] University Medicine Rostock, Institute of Pathology, Strempelstraße 14, 18055 Rostock, Germany.
RP Schneider, B (reprint author), University Medicine Rostock, Institute of Pathology, 18055 Rostock, Germany.
EM bjoern.schneider@med.uni-rostock.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1319
EP 1325
DI 10.1007/s12253-017-0371-7
PG 7
ER
PT J
AU Singh, A
Singh, N
Behera, D
Sharma, S
AF Singh, Amrita
Singh, Navneet
Behera, Digambar
Sharma, Siddharth
TI Genetic Investigation of Polymorphic OGG1 and MUTYH Genes Towards Increased Susceptibility in Lung Adenocarcinoma and its Impact on Overall Survival of Lung Cancer Patients Treated with Platinum Based Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Polymorphism; Lung cancer; Overall survival; Chemotherapy; OGG1; MUTHY
ID Polymorphism; Lung cancer; Overall survival; Chemotherapy; OGG1; MUTHY
AB Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway. OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer cases and 330 controls was followed by genotyping making use of PCRRFLP. Logistic regression was done to analyze the risk towards lung cancer. Patients were followed through telephonic conversation. Kaplan meier and Cox-regression were used for survival analysis. OGG1 presented a high risk towards lung cancer (CG: OR = 2.44, p = 0.0003; CG + GG: OR = 1.88, p = 0.0093). On the same lines adenocarcinoma for OGG1 were potent risk factors towards lung cancer (CG: OR = 4.72, p = 0.0002; CG + GG: OR = 3.63, p = 0.0018). Single allelic carriers for MUTYH gene imposed a high risk towards overall lung susceptibility and for all the three histology. Stratified analysis for chemotherapeutic drugs revealed administration of Cisplatin/Carboplatin + Pemtrexed for OGG1Ser 326 Cys showed a better survival (MST CG vs. CC: 9.1 vs. 0.56, p = <0.0001; HR =0.051, p = 0.0025). Whereas, MUTYH Gln324His showed a smaller survival for mutant genotype (CC) (MST CC vs. GG: 4.0 vs. 9.4, p = 0.05; HR = 1.75, p = 0.26). Single allelic carriers for both OGG1 and MUTYH were risk factors towards lung cancer. The risk was amplified on combining both OGG1 and MUTYH.
C1 [Singh, Amrita] Thapar University, Department of Biotechnology, 147002 Patiala, Punjab, India.
[Singh, Navneet] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary MedicineChandigarh, India.
[Behera, Digambar] Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Department of Pulmonary MedicineChandigarh, India.
[Sharma, Siddharth] Thapar University, Department of Biotechnology, 147002 Patiala, Punjab, India.
RP Sharma, S (reprint author), Thapar University, Department of Biotechnology, 147002 Patiala, India.
EM siddharthsharma.phd@thapar.edu
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Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T, Sugimura H, 2011, Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer. J Pathol 225:414–423
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1327
EP 1340
DI 10.1007/s12253-017-0372-6
PG 14
ER
PT J
AU Raphael, J
Nofech-Mozes, Sh
Paramsothy, Th
Li, N
Gandhi, S
AF Raphael, Jacques
Nofech-Mozes, Sharon
Paramsothy, Thivaher
Li, N
Gandhi, Sonal
TI Tumor Infiltrating Lymphocytes in Breast Cancer Patients with Progressive Disease during Neoadjuvant Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Disease progression; Neoadjuvant chemotherapy; Tumor infiltrating lymphocytes
ID Breast cancer; Disease progression; Neoadjuvant chemotherapy; Tumor infiltrating lymphocytes
AB A minority of breast cancer (BC) patients progress during neoadjuvant chemotherapy (NCT). The aim of this study was to assess the value of Tumor infiltrating lymphocytes (TILs) in such a high-risk population where valid biomarkers are eagerly needed. A retrospective review identified BC patients who either progressed during NCT or achieved a pathologic complete response (pCR). An experienced BC pathologist semi-quantified stromal TILs in pre-treatment core biopsies using hematoxylin and eosin stained slides. The primary outcome was to compare the levels of TILs between the 2 groups as a continuous and categorical variable using the t-test and X2 test as appropriate. The secondary outcome was to compare survival outcomes between patients with high versus low TILs level using the log-rank test. Fifty patients were successfully identified and assessed for TILs: 21 progressed during NCT and 29 had a pCR. Patients with progressive disease were older with more advanced disease (p = 0.03, p = 0.0001 respectively). A significantly lower mean level of TILs was found in patients with progressive disease compared to patients with pCR: 14.3% (Standard Deviation (SD): 16.9) versus 32.8% (SD: 31), p = 0.01). The level of TILs was neither associated with baseline characteristics nor with survival outcomes. BC patients progressing during NCT have low TILs levels compared to patients with pCR. Prospective studies are needed to establish the utility of TILs as early biomarkers of tumor response, particularly in patients with disease progression who need novel treatment approaches.
C1 [Raphael, Jacques] Sunnybrook Health Sciences Centre, Department of Medicine, Division of Medical Oncology, 2075 Bayview Avenue, M4N3M5 Toronto, ON, Canada.
[Nofech-Mozes, Sharon] Sunnybrook Health Sciences Centre, Department of PathologyToronto, ON, Canada.
[Paramsothy, Thivaher] Sunnybrook Health Sciences Centre, Department of Medicine, Division of Medical Oncology, 2075 Bayview Avenue, M4N3M5 Toronto, ON, Canada.
[Li, N] Sunnybrook Research InstituteToronto, ON, Canada.
[Gandhi, Sonal] Sunnybrook Health Sciences Centre, Department of Medicine, Division of Medical Oncology, 2075 Bayview Avenue, M4N3M5 Toronto, ON, Canada.
RP Raphael, J (reprint author), Sunnybrook Health Sciences Centre, Department of Medicine, Division of Medical Oncology, M4N3M5 Toronto, Canada.
EM raphaeljack13@hotmail.com
CR Kong X, Moran MS, Zhang N et al, 2011, Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer 47:2084–2090
Broglio KR, Quintana M, Foster M et al, 2016, Association of Pathologic Complete Response to Neoadjuvant therapy in HER2- positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol 2(6):751–760
Cortazar P, Zhang L, Untch M et al, 2014, Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172
De Mattos-Arruda L, Shen R, Reis-Filho JS, Cortes J, 2016, Translating neoadjuvant therapy into survival benefits: one size does not fit all. Nat Rev Clin Oncol 13(9):566–579
Weigelt B et al, 2005, Breast cancer metastasis: markers and models. Nat Rev Cancer 5:591–602
Von Minckwitz G, Blohmer JU, Costa SD et al, 2013, Responseguided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 31(29):3623–3630
Kim KI, Lee KH, Kim TR et al, 2014, Ki-67 as a predictor of response to Neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer 17(1):40–46
Denkert C, Loibl S, Noske A et al, 2010, Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28(1):105–113
Von Minckwitz G, Untch M, Nuesch E et al, 2011, Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125:145–156
Mamounas EP, Cortazar P, Zhang L, et al, 2014, Loco-regional recurrence after neoadjuvant chemotherapy: Pooled analysis results from the Collaborative Trials in Neoadjuvant Breast Cancer, CTNeoBC). J Clin Oncol 32(Suppl 26; Abstr 61)
Zambetti M, Mansutti M, Gomez P et al, 2012, Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design, ECTO II). Breast Cancer Res Treat 132(3):843–851
Straver ME, Rutger EJ, Rodenhuis S et al, 2010, The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy. Ann Surg Oncol 17:2411–2418
CaudleAS,Gonzalez-Angulo AM,Hunt KK et al, 2010, Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28(11):1821–1828
Raphael J, Paramsothy T, Li N, Lee J, Gandhi SA, 2017, Singleinstitution experience of salvage therapy for patients with early and locally advanced breast cancer who progress during neoadjuvant chemotherapy. Breast Cancer Res Treat 163(1):11–19
Denkert C, von Minckwitz G, Brase JC et al, 2015, Tumorinfiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 33:983–991
West NR, Milne K, Truong PT et al, 2011, Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res 13:R126
Yamaguchi R, Tanaka M, Yano A et al, 2012, Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer. Hum Pathol 43: 1688–1694
Loi S, Sirtaine N, Piette F et al, 2013, Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 31:860–867
Adams S, Gray RJ, Demaria S et al, 2014, Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol 32:2959–2966
Loi S, Michiels S, Salgado R et al, 2014, Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 25(8):1544–1550
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Hammond ME, Hayes DF, Dowsett M et al, 2010, ASCO/CAP guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28: 2784–2795
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Pennisi A, Kieber-Emmons T, Makhoul I, Hutchins L, 2016, Relevance of pathological complete response after Neoadjuvant therapy for breast cancer. Breast Cancer, Auckl, 10:103–106
Salgado R, Denkert C, Demaria S et al, 2015, The evaluation of tumor-infiltrating lymphocytes, TILs, in breast cancer: recommendations by an international TILs working group 2014. Ann Oncol 26(2):259–271
Ingold Heppner B, Loibl S, Denkert C, 2016, Tumor-infiltrating lymphocytes: a promising biomarker in breast cancer. Breast Care, Basel, 11(2):96–100
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Harris LN, Ismaila N, McShane LM et al, 2016, Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 34(10):1134–1150
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1341
EP 1347
DI 10.1007/s12253-017-0368-2
PG 7
ER
PT J
AU Matyas, P
Postyeni, E
Komlosi, K
Szalai, R
Bene, J
Magyari, L
Melegh, B
Hadzsiev, K
AF Matyas, Petra
Postyeni, Etelka
Komlosi, Katalin
Szalai, Renata
Bene, Judit
Magyari, Lili
Melegh, Bela
Hadzsiev, Kinga
TI Age-Related Hearing Impairment Associated NAT2, GRM7, GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NAT2; GRM7; GRHL2; ARHI; Roma; Hungarian
ID NAT2; GRM7; GRHL2; ARHI; Roma; Hungarian
AB Age-related hearing impairment (ARHI) is the most frequent sensory disease in the elderly, which is caused by an interaction between genetic and environmental factors. Here we examined the ethnic differences, allele and genotype frequencies of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and healthy and hearing impaired Roma people. Study populations of healthy Hungarian and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7, rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using a PCR-RFLP method. We found significant differences in minor allele frequencies for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05). The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361 variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs. 32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and 26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the frequency of GGT, GAC and GAT haplotypes was significantly higher in the Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and 1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations that might have important implications for the preventive and therapeutic treatments in this population.
C1 [Matyas, Petra] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Postyeni, Etelka] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Komlosi, Katalin] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Szalai, Renata] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Bene, Judit] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Magyari, Lili] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Melegh, Bela] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
[Hadzsiev, Kinga] University of Pecs, Department of Medical Genetics and Child Development, Szigeti 12, H-7624 Pecs, Hungary.
RP Melegh, B (reprint author), University of Pecs, Department of Medical Genetics and Child Development, H-7624 Pecs, Hungary.
EM melegh.bela@pte.hu
CR Staecker H, ZhengQY, Van DeWater TR, 2001, Oxidative stress in aging in the C57B16/J mouse cochlea. Acta Otolaryngol 121(6): 666–672
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Van Laer L, Van Eyken E, Fransen E, Huyghe JR, Topsakal V, Hendrickx JJ, Hannula S, Maki-Torkko E, Jensen M, Demeester K, Baur M, Bonaconsa A, Mazzoli M, Espeso A, Verbruggen K, Huyghe J, Huygen P, Kunst S, Manninen M, Konings A, Diaz- Lacava AN, Steffens M, Wienker TF, Pyykko I, Cremers CW, Kremer H, Dhooge I, Stephens D, Orzan E, Pfister M, Bille M, Parving A, Sorri M, Van de Heyning PH, Van Camp G, 2008, The grainyhead like 2 gene, GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. Hum Mol Genet 17(2):159–169
Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V, Schmidt C, Abicht A, Lochmuller H, Tordai A, Kalmar L, Nagy M, Karcagi V, Jeanpierre M, Herczegfalvi A, Beeson D, Venkataraman V, Warwick Carter K, Reeve J, de Pablo R, Kucinskas V, Kalaydjieva L, 2004, Mutation history of the roma/gypsies. Am J Hum Genet 75(4):596–609
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ColingDE,Yu KC, Somand D, Satar B, Bai U, Huang TT, Seidman MD, Epstein CJ, Mhatre AN, Lalwani AK, 2003, Effect of SOD1 overexpression on age- and noise-related hearing loss. Free Radic Biol Med 34(7):873–880
Ates NA, UnalM, Tamer L, Derici E, Karakas S, Ercan B, Pata YS, Akbas Y, Vayisoglu Y, Camdeviren H, 2005, Glutathione Stransferase gene polymorphisms in presbycusis. Otol Neurotol 26(3):392–397
Pujol R, Puel JL, Gervais d'Aldin C, Eybalin M, 1993, Pathophysiology of the glutamatergic synapses in the cochlea. Acta Otolaryngol 113(3):330–334
Steinbach S, Lutz J, 2007, Glutamate induces apoptosis in cultured spiral ganglion explants. Biochem Biophys Res Commun 357(1): 14–19
Sipeky C, Matyas P, Melegh M, Janicsek I, Szalai R, Szabo I, Varnai R, Tarlos G, Ganczer A, Melegh B, 2014, Lower carrier rate of GJB2 W24X ancestral Indian mutation in Roma samples from Hungary: implication for public health intervention. Mol Biol Rep 41(9):6105–6110
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1349
EP 1355
DI 10.1007/s12253-018-0388-6
PG 7
ER
PT J
AU Sastre-Heres, JA
Iglesias, I
Alaguero-Calero, M
Ruiz-Sanchez, D
Garcia-Diaz, B
Pena-Diaz, J
AF Sastre-Heres, Jose Alejandro
Iglesias, Irene
Alaguero-Calero, Miguel
Ruiz-Sanchez, Daniel
Garcia-Diaz, Benito
Pena-Diaz, Jaime
TI Comparative Study of Different Classification Models in Renal-Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell cancer; Classification; Predictive; Prognostic
ID Renal cell cancer; Classification; Predictive; Prognostic
AB The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good shortand long-term prognostics while possessing better predictive ability and a more equal distribution of patients.
C1 [Sastre-Heres, Jose Alejandro] Hospital San Juan de Dios de Zaragoza, Servicio de Farmacia, C/ Paseo Colon n°14, 50006 Zaragoza, Spain.
[Iglesias, Irene] Ciudad Universitaria, University Complutense of Madrid, Faculy of Pharmacy, Plaza Ramon y Cajal, 28040 Madrid, Spain.
[Alaguero-Calero, Miguel] Hospital Universitario Central de Asturias, Hospital Pharmacy Department, C/ Julian Claveria s/n, 33006 Oviedo, Asturias, Spain.
[Ruiz-Sanchez, Daniel] Hospital Universitario Central de Asturias, Hospital Pharmacy Department, C/ Julian Claveria s/n, 33006 Oviedo, Asturias, Spain.
[Garcia-Diaz, Benito] Hospital Universitario Severo Ochoa, C/ Avenida de Orellana, s/n, 28911 Leganes, Madrid, Spain.
[Pena-Diaz, Jaime] University of Granada, Spanish Society of Hospital Pharmacy, Faculty of Pharmacy, Campus Universitario de Cartuja, 18071 Granada, Spain.
RP Sastre-Heres, JA (reprint author), Hospital San Juan de Dios de Zaragoza, Servicio de Farmacia, 50006 Zaragoza, Spain.
EM asastre@ohsjd.es
CR Ljungberg B, Hanbury DC, Kuczyk MA et al, 2007, Renal cell carcinoma guideline. Eur Urol 51:1502–1510
Sanchez Folgueras MV, Palacio Vazquez IP, 2009, Registro hospitalario de tumores del Servicio de Salud del Principado de Asturias. Ano 2009. Astursalud website. http://www.hca.es/huca/ web/contenidos/servicios/rt/rt2012/rt2012.pdf. Accessed 05 Oct 2015
ChowW, Gridley G, Fraumeni J et al, 2000, Obesity, hypertension and the risk of kidney cancer inmen. N Engl J Med 343:1305–1311
Escudier B, Eisen T, Porta C et al, 2014, Clinical practice guidelines renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up clinical practice guidelines. Ann Oncol 25(3):49–56
NCNN Clinical practice guidelines in oncology. Version 1.2013. Kidney cancer. The National Comprehensive Cancer Network website http://www.nccn.org/professionals/physician_gls/f_ guidelines_nojava.asp#site. Accessed 05 Oct 2015
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Mekhail TM,Abou-JawdeRM, Boumerhi Get al, 2005)Validation and extension of the memorial Sloan- Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23(4):832–841
Hudes G, Carducci M, Tomczak P et al, 2007, Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281
Escudier B, Choueiri TK, Oudard S et al, 2007, Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941. J Urol 178(5):1901–1905
Choueiri TK, Garcia JA, Elson P et al, 2007, Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer 110(3):543–550
Heng DY, Xie W, Regan MM et al, 2009, Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27(34):5794–5799
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Patil S, Figlin RA, Hutson TE et al, 2011, Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22(2):295–300
Heagerty PJ, Zheng Y, 2005, Survival model predictive accuracy and ROC curves. Biometrics 61(1):92–105
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Karakiewcz P, Sun M, Bellmunt J et al, 2011, Prediction of progression-free survival rates after bevacizumab plus interferon alone in patients with metastatic renal cell carcinoma: comparion of a normogram to the Motzer criteria. Eur Urol 60:48–56
Sun M, Shariat SF, Cheng C et al, 2011, Prognostic factors and predictive models in renal cell carcinoma: a contemporary review. Eur Urol 60:644–661
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1357
EP 1362
DI 10.1007/s12253-018-0385-9
PG 6
ER
PT J
AU Santos Cirqueira, C
Sousa Felipe-Silva, A
Wakamatsu, A
Vieira Marins, L
Cavalcanti Rocha, E
Sobroza de Mello, E
Avancini Ferreira Alves, V
AF Santos Cirqueira, Cinthya
Sousa Felipe-Silva, Aloisio
Wakamatsu, Alda
Vieira Marins, Lidiane
Cavalcanti Rocha, Eziel
Sobroza de Mello, Evandro
Avancini Ferreira Alves, Venancio
TI Immunohistochemical Assessment of the Expression of Biliary Transportation Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ATP-binding cassette transporters; Hepatocellular carcinoma; Cholangiocarcinoma; Immunohistochemistry
ID ATP-binding cassette transporters; Hepatocellular carcinoma; Cholangiocarcinoma; Immunohistochemistry
AB Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays. The immunohistochemical reactivity (IHC) of these transporters was assessed in tissue microarrays of 80 HCC and 56 CC cases using monoclonal antibodies and compared with anatomopathological (AP) variables. The positivity of MRP2 was observed in 92.3% of HCC and in 96.3% of CC. The detection of high MRP2 expression in HCC was not significantly different (p > 0.05) according to the size, number of nodules architectural pattern and growth pattern of HCC and CC. Regarding histological grades, 22/22 well moderately differentiated HCC versus 50/56 poorly differentiated HCC were positive for MRP2. A trend for lower expression in poor differentiation HCC was found. And 50/50 well/moderately differentiated CC versus 2/4 poorly/undifferentiated CC were positive for MRP2. This result showed a reduced expression (p = 0,0004) in poorly differentiated CC. MRP3 positivity was observed in 18.8% of HCC and was not significantly different according to AP parameters. MRP3 was expressed in 44.5% CC, with a trend for lower expression in less differentiated CC and significantly lower rates in the ductular histological subtype (p = 0.023). The high expression of MRP2 in HCC and in CC is conserved regardlessmost of the anatomopathological parameters, except for a trend of lower expression in less differentiated HCC and CC. The observation of lower MRP3 expression in less differentiated CC and, especially, in the histological subtype with expression of hepatic progenitor cell phenotypes leads to future opportunities to evaluate the expression of this marker in cholangiocarcinomas.
C1 [Santos Cirqueira, Cinthya] Instituto Adolfo Lutz, Centro de Patologia, Nucleo de Anatomia PatologicaSao Paulo, Brazil.
[Sousa Felipe-Silva, Aloisio] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
[Wakamatsu, Alda] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
[Vieira Marins, Lidiane] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
[Cavalcanti Rocha, Eziel] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
[Sobroza de Mello, Evandro] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
[Avancini Ferreira Alves, Venancio] Sao Paulo University School of Medicine, Department of PathologySao Paulo, Brazil.
RP Santos Cirqueira, C (reprint author), Instituto Adolfo Lutz, Centro de Patologia, Nucleo de Anatomia Patologica, Sao Paulo, Brazil.
EM cinthyacirqueira@yahoo.com.br
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1363
EP 1371
DI 10.1007/s12253-018-0386-8
PG 9
ER
PT J
AU Srividya, A
Giridhar, H
Vishwanath, S
Chakraborty, A
AF Srividya, Arjuna
Giridhar, B. Hosmane
Vishwanath, Silpa
Chakraborty, Anirban
TI Profiling of Germline Mutations in Major Hotspot Codons of TP53 Using PCR-RFLP
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tumor suppressor protein TP53; Mutation; Hotspot codon; Homoallelic mutation; Heteroallelic mutation; Cancer
ID Tumor suppressor protein TP53; Mutation; Hotspot codon; Homoallelic mutation; Heteroallelic mutation; Cancer
AB Tumor suppressor protein, TP53 also known as the "guardian of the genome" plays a key role in preventing malignant transformation. Almost 50% of human tumors carry mutations in this gene; in the remaining tumors, the TP53 network is functionally inoperative. The majority of TP53 mutations are missense mutations and more than 90% of the missense mutations affect specific codons in the DNA-binding domain, called "hotspot codons". The present study was aimed at analyzing the germline mutation status of four hotspot codons in TP53 namely, codon 175, codon 245, codon 248 (within the DNA binding domain) and codon 72 (outside the DNA binding domain) in cancer cases encountered in a tertiary care hospital in South India by PCR-RFLP. The casecontrol study included 85–10 subjects respectively. The results of the study indicated that majority of the cancer cases did not harbor germline mutations in the four hot spot codons of TP53. The study further highlights the usefulness of PCR-RFLP as a simple and cost effective tool for checking gene mutations.
C1 [Srividya, Arjuna] Nitte University Centre for Science Education and Research (NUCSER), Division of Molecular Genetics and Cancer, Kotekar-Beeri Road, Deralakatte, 575018 Mangaluru, India.
[Giridhar, B. Hosmane] K S Hegde Medical Hospital, Department of Pulmonary Medicine, 575018 Mangaluru, India.
[Vishwanath, Silpa] K S Hegde Medical Hospital, Department of Surgery, 575018 Mangaluru, India.
[Chakraborty, Anirban] Nitte University Centre for Science Education and Research (NUCSER), Division of Molecular Genetics and Cancer, Kotekar-Beeri Road, Deralakatte, 575018 Mangaluru, India.
RP Chakraborty, A (reprint author), Nitte University Centre for Science Education and Research (NUCSER), Division of Molecular Genetics and Cancer, 575018 Mangaluru, India.
EM anirban@nitte.edu.in
CR Chakraborty A, Uechi T, Kenmochi N, 2011, Guarding the ‘translation apparatus’: defective ribosome biogenesis and the p53 signaling pathway. WIREs RNA 2:507–522
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1373
EP 1377
DI 10.1007/s12253-018-0394-8
PG 5
ER
PT J
AU Sticz, T
Molnar, A
Danko, T
Hujber, Z
Petovari, G
Nagy, N
Vegso, Gy
Kopper, L
Sebestyen, A
AF Sticz, Tamas
Molnar, Anna
Danko, Titanilla
Hujber, Zoltan
Petovari, Gabor
Nagy, Noemi
Vegso, Gyula
Kopper, Laszlo
Sebestyen, Anna
TI The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon carcinoma; EGFR inhibitor; mTOR inhibitor; Resistance
ID Colon carcinoma; EGFR inhibitor; mTOR inhibitor; Resistance
AB Several monoclonal antibodies and inhibitors targeting signalling pathways are being used in personalised medicine. Anti-EGFR antibodies seem to be effective, however, therapy resistance often occurs in colon carcinoma cases. mTOR inhibitors (mTORIs) could have a potential role in the breakthrough of therapy resistance. The mTOR activity related protein expression patterns and the in vitro effects of EGFR inhibitors (EGFRIs), mTORIs and their combinations were studied in different colon carcinoma cell lines (with different genetic backgrounds). Alamar Blue test and flow cytometry were used to analyse the in vitro proliferation and apoptotic effects of cetuximab, gefitinib, cisplatin, rapamycin, PP242 and NVP-BEZ235. The expressions of mTOR activity related proteins (p-70S6K, p-S6, Rictor, p-mTOR, Raptor) were studied by Western blot, immunocytochemistry and Duolink staining. The EGFRI resistance of the studied colon carcinoma cell lines related to their known mutations were confirmed, neither gefitinib nor cetuximab inhibited the proliferation or induced apoptosis in vitro. Individual differences in Rictor and Raptor expressions were detected by Western blot and immunocytochemistry beside elevated mTOR activity of these different colon carcinoma cell lines. These expression patterns correlated to the mTORIs sensitivity differences, moreover, mTORIs could enhance the effects of EGFRIs and other in vitro treatments. Our results suggest that mTORI combinations could be helpful in both EGFRI and platinum-based therapy of colon carcinomas. Moreover, we suggest determining both mTOR complex activity and mutations in Akt/mTOR signalling pathways for selecting the appropriate mTORIs and patients in potential future combination treatments.
C1 [Sticz, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Molnar, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Hujber, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Nagy, Noemi] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Vegso, Gyula] Semmelweis University, Department of Transplantation and Surgery, Ulloi ut 26, H-1085 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Sebestyen, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM hsebanna@gmail.com;anna@korb1.sote.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1379
EP 1386
DI 10.1007/s12253-018-0434-4
PG 8
ER
PT J
AU Ansari, H
Shahrisa, A
Tahmasebi Birgani, Y
Tahmasebi Birgani, M
Hajjari, M
Mohammadi Asl, J
AF Ansari, Hossein
Shahrisa, Arman
Tahmasebi Birgani, Yaser
Tahmasebi Birgani, Maryam
Hajjari, Mohammadreza
Mohammadi Asl, Javad
TI Long Noncoding RNAs in Colorectal Adenocarcinoma; an in silico Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; Biomarker; Long noncoding RNAs; SNHG6; PVT1; ZFAS1
ID Cancer; Biomarker; Long noncoding RNAs; SNHG6; PVT1; ZFAS1
AB Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are involved in critical signaling pathways including cell cycle and apoptosis so it is not surprising to see their altered expression in human tumors. Colorectal adenocarcinoma is one the most frequent malignancies worldwide. The role of lncRNAs in colorectal adenocarcinoma is not well understood. To study the significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved lncRNAs from HGNC. The genes were imported into the cBioPortal database for transcriptomic analyses. We queried all the samples from TCGA provisional colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA dysregulation with Z-score: ±2. The lncRNA which was altered in most of the patients were considered as "significant lncRNA" for further analyses. We considered the association of candidate lncRNAs with clinicopathologic parameters of samples including tumor disease anatomic site, neoplasm histologic types, tumor stage and survival. We also compute the specificity of the significant lncRNAs expression in colorectal adenocarcinoma comparing with other human cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1 allocated the maximum alteration among the colorectal cases. The expression of SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while the PVT1 showed the same expression levels in both tissues. However, we found that upregulation of PVT1 has been reduced the overall survival in patients. Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for experimental research on colorectal adenocarcinoma to discover novel biomarker for this prevalent cancer.
C1 [Ansari, Hossein] Islamic Azad University, Ahvaz Branch, Department of BiotechnologyAhvaz, Iran.
[Shahrisa, Arman] Tarbiat Modares University, Faculty of Biosciences, Department of Molecular GeneticsTehran, Iran.
[Tahmasebi Birgani, Yaser] Ahvaz Jundishapur University of Medical Sciences, School of Public Health, Department of Environmental Health EngineeringAhvaz, Iran.
[Tahmasebi Birgani, Maryam] Ahvaz Jundishapur University of Medical Sciences, School of Medicine, Department of Medical GeneticsAhvaz, Iran.
[Hajjari, Mohammadreza] Shahid Chamran University of Ahvaz, Faculty of Sciences, Department of GeneticsAhvaz, Iran.
[Mohammadi Asl, Javad] Ahvaz Jundishapur University of Medical Sciences, School of Medicine, Department of Medical GeneticsAhvaz, Iran.
RP Shahrisa, A (reprint author), Tarbiat Modares University, Faculty of Biosciences, Department of Molecular Genetics, Tehran, Iran.
EM shahrisa.arman@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1387
EP 1394
DI 10.1007/s12253-018-0428-2
PG 8
ER
PT J
AU Ghali, MR
Mahjoub, S
Zaied, S
Bhiri, H
Bahia, W
Mahjoub, T
Almawi, YW
AF Ghali, M Rabeb
Mahjoub, Sana
Zaied, Sonia
Bhiri, Hanen
Bahia, Wael
Mahjoub, Touhami
Almawi, Y Wassim
TI Association of Genetic Variants in NF-kB with Susceptibility to Breast Cancer: a Case Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Allele; Breast cancer; Haplotype; Metastasis; NF-κB
ID Allele; Breast cancer; Haplotype; Metastasis; NF-κB
AB Insofar as altered NF-κB signaling stemming from the presence of specific genetic variants in NF-κB gene contribute to cancer pathogenesis, this study evaluated the association between NF-κB rs147574894/I552V, rs148626207/M860T rs3774937 and rs1598859 variants and breast cancer and associated features and complications. This was a retrospective case-control study, which involved 207 women with breast cancer, and 214 cancer-free women who served as controls. NF-κB genotyping was done by real-time PCR. Significantly higher rs3774937 minor allele frequencies (MAF), and lower rs147574894 MAF were seen among breast cancer patients, thereby imparting disease susceptibility and protective nature to these variants, respectively. Significant association of rs3774937 and rs147574894 genotypes with breast cancer was seen under the dominant model. Histological type and grade, molecular type, Her2 positivity and ER+/Her2- correlated positively, while distant metastasis negatively correlated with rs3774937. On the other hand, rs147574894 negatively correlated with histological type and grade, tumor size, Her2 positivity, molecular type, and ER+/Her2-, while rs148626207 correlated positively with histological grade, but negatively with distant metastasis and triple-negative status. Breast cancer-susceptible and –protective 4-locus haplotypes were also identified. This is the first report that addresses the contribution of NF-κB variants to the pathogenesis of breast cancer in Middle Eastern-North African population, and the first to document positive association of rs3774937 with breast cancer.
C1 [Ghali, M Rabeb] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Mahjoub, Sana] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Zaied, Sonia] CHU Fattouma Bourguiba, Department of Clinical OncologyMonastir, Tunisia.
[Bhiri, Hanen] CHU Fattouma Bourguiba, Department of Clinical OncologyMonastir, Tunisia.
[Bahia, Wael] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Mahjoub, Touhami] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Almawi, Y Wassim] El Manar University, Faculty of Sciences of TunisTunis, Tunisia.
RP Almawi, YW (reprint author), El Manar University, Faculty of Sciences of Tunis, Tunis, Tunisia.
EM wassim.almawi@outlook.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1395
EP 1400
DI 10.1007/s12253-018-0452-2
PG 6
ER
PT J
AU Evans, M
O’Sullivan, B
Smith, M
Hughes, F
Mullis, T
Trim, N
Taniere, P
AF Evans, Matthew
O’Sullivan, Brendan
Smith, Matthew
Hughes, Frances
Mullis, Tina
Trim, Nicola
Taniere, Philippe
TI Large-Scale EGFR Mutation Testing in Clinical Practice: Analysis of a Series of 18,920 Non-Small Cell Lung Cancer Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; Lung cancer; Molecular pathology; TKI
ID EGFR; Lung cancer; Molecular pathology; TKI
AB We make use of a very large dataset of non-small cell lung cancer specimens to examine the molecular epidemiology of EGFR mutations, particularly with respect to rare and compound mutations, and to non-adenocarcinoma histological subtypes. We also demonstrate the feasibility of large-scale EGFR mutation screening using the full range of specimens encountered in routine practice. We retrospectively reviewed 18,920 unselected EGFR mutation results from our centre between July 2009 and October 2016, using Qiagen’s therascreen EGFR RGQ PCR Kit. Mutation rates were correlated with patient demographics and tumour histology. Our testing success rate was 93.9%, with similar success rates using histological and cytological specimens. Rare, potentially-targetable mutations accounted for 9.5% of all mutations detected. We identified a 2.5% mutation rate in tumours diagnosed as squamous cell carcinomas. There was a trend towards increasing EGFR mutation rates with increasing age, and while Del19 was the commonest mutation in the young, L858R predominated in the elderly. We found that EGFR mutation heterogeneity is rare within tumours and between primary and metastatic deposits. Our data demonstrate that large-scale, reflex EGFR mutation testing is feasible and affordable in the context of a publicly-funded health system. Furthermore, we have shown that the use of techniques sensitive only to classical mutations and selection of patients on the grounds of age, sex and histology denies patients access to potentially beneficial TKI therapy.
C1 [Evans, Matthew] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[O’Sullivan, Brendan] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[Smith, Matthew] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[Hughes, Frances] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[Mullis, Tina] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[Trim, Nicola] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
[Taniere, Philippe] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2GW Birmingham, UK.
RP Evans, M (reprint author), Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, B15 2GW Birmingham, UK.
EM matthew.evans7@nhs.net
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1401
EP 1409
DI 10.1007/s12253-018-0460-2
PG 9
ER
PT J
AU Cui, M
Chang, Y
Fang, QG
Du, W
Wu, JF
Wang, JH
Liu, ShT
Luo, SX
AF Cui, Meng
Chang, Yu
Fang, Qi-Gen
Du, Wei
Wu, Jun-Fu
Wang, Ji-Heng
Liu, Shan-Ting
Luo, Su-Xia
TI Non-Coding RNA Pvt1 Promotes Cancer Stem Cell–Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PVT1; Nasopharyngeal carcinoma; miR-1207; PI3K/AKT; Tumor stemcell
ID PVT1; Nasopharyngeal carcinoma; miR-1207; PI3K/AKT; Tumor stemcell
AB Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor. lncRNA-PVT1 can promote the proliferation of carcinoma cells, and induce cells to have stem cell-like potentials. However, the function of PVT1 in NPC cells is not clear. The expressions of lncRNA-PVT1 and the expressions of the stem cell markers in NPC tissues or cell lines were investigated by qRTPCR or western blot. The cell proliferation, and the ability of NPC cells to form spherical, clonal colonies were investigated by MTT assay, colony formation assay, and tumor-sphere formation assay. Cancer stem cells surface markers were detected by flow cytometry and western blot. PI3K/AKT signal activation in NPC cells was determined by western blot. PVT1 was significantly up-regulated in both NPC tissues and cell lines and associated with poor prognosis. PVT1 knockdown reduced NPC cells viability, clonogenicity, the cell surface CD44+/CD24− stem phenotype, and the expressions of the stem cell markers in NPC cells, including Oct4, c-Myc, SOX2, and ALDH. Furthermore, PVT1 negatively regulates the expression levels of miR-1207 in NPC cells and spheres cells, which is critical for NPC stemness. Knockdown of miR-1207 promoted stem phenotype and the expressions of the stem cell markers in NPC cells. Moreover, phosphor-PI3K (p-PI3K) and phosphor-AKT (p-AKT) were found to be down-regulated after PVT1 siRNAs transfection in NPC cells. And miR-1207 inhibitor transfection reversed the all the effects brought by PVT1 knockdown. Pvt1 promotes cancer stem cell–like properties in NPC cells via inhibiting miR-1207 and activating the PI3K/AKT signal pathway.
C1 [Cui, Meng] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Chang, Yu] First Affiliated Hospital of Zhengzhou University, Department of Oncology, 450008 Zhengzhou, China.
[Fang, Qi-Gen] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Du, Wei] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Wu, Jun-Fu] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Wang, Ji-Heng] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Liu, Shan-Ting] Affiliated Cancer Hospital of Zhengzhou University, Department of Head & Neck and Thyroid, 450008 Zhengzhou, China.
[Luo, Su-Xia] Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 450008 Zhengzhou, China.
RP Luo, SX (reprint author), Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 450008 Zhengzhou, China.
EM luosuxia8275@sina.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1411
EP 1422
DI 10.1007/s12253-018-0453-1
PG 12
ER
PT J
AU Boldrini, L
Bartoletti, R
Giordano, M
Manassero, F
Selli, C
Panichi, M
Galli, L
Farci, F
Faviana, P
AF Boldrini, Laura
Bartoletti, Riccardo
Giordano, Mirella
Manassero, Francesca
Selli, Cesare
Panichi, Marco
Galli, Luca
Farci, Fabiola
Faviana, Pinuccia
TI C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; C-myc; HIF-1α; GSTP1; TKT; ERG
ID Prostate cancer; C-myc; HIF-1α; GSTP1; TKT; ERG
AB To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis.We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.
C1 [Boldrini, Laura] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Bartoletti, Riccardo] University of Pisa, Department of Translational Research and New TechnologiesPisa, Italy.
[Giordano, Mirella] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Manassero, Francesca] Pisa University, Division of UrologyPisa, Italy.
[Selli, Cesare] University of Pisa, Department of Translational Research and New TechnologiesPisa, Italy.
[Panichi, Marco] Pisa University, Department of RadiotherapyPisa, Italy.
[Galli, Luca] Pisa University, Division of Medical OncologyPisa, Italy.
[Farci, Fabiola] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Faviana, Pinuccia] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
RP Boldrini, L (reprint author), University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, 56126 Pisa, Italy.
EM laura.boldrini@med.unipi.it
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1423
EP 1429
DI 10.1007/s12253-018-0479-4
PG 7
ER
PT J
AU Comert, KG
Basaran, D
Akkoz, EH
Celik, B
Sinaci, S
Turkmen, O
Karalok, A
Kandemir, O
Turan, T
AF Comert, Kimyon Gunsu
Basaran, Derman
Akkoz, Ergin Hayriye
Celik, Burcin
Sinaci, Selcan
Turkmen, Osman
Karalok, Alper
Kandemir, Olcay
Turan, Taner
TI Blood Vessel Invasion in Endometrial Cancer Is One of the Mechanisms of Spread to the Cervix
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lympho-vascular invasion; Podoplanin; CD31; Blood vessel; Endometrial cancer
ID Lympho-vascular invasion; Podoplanin; CD31; Blood vessel; Endometrial cancer
AB To evaluate the association between type of invaded vessels (blood or lymphatic) and cervical involvement in endometrial cancer (EC). Pathological slides of 93 patients with EC who had vascular space invasion in hematoxylin-eosin staining underwent immunohistochemical assay with CD31 and podoplanin. CD31 and podoplanin were used to identify blood and lymphatic invaded vessels, respectively. Cervical stromal invasion (CSI) was determined in 21 (30%) patients. The rate of CD31- positivity was significantly higher in patients with CSI than without (76.2 and 34.7%, p = 0.001; respectively). Podoplaninpositivity was determined in 47.6 and 81.6% of patients with and without CSI, respectively (p = 0.005). Age, myometrial invasion and the combination of CD31-positivity with podoplanin-negativity were found as independent predictors for CSI. Blood vessel invasion is an important factor for CSI in EC. Blood vessel invasion rather than lymphatic vessel invasion is one of the predominant ways by which EC spreads to the cervix.
C1 [Comert, Kimyon Gunsu] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
[Basaran, Derman] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
[Akkoz, Ergin Hayriye] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Celik, Burcin] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Pathology DivisionAnkara, Turkey.
[Sinaci, Selcan] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
[Turkmen, Osman] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
[Karalok, Alper] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
[Kandemir, Olcay] Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Department of PathologyAnkara, Turkey.
[Turan, Taner] Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology DepartmentAnkara, Turkey.
RP Comert, KG (reprint author), Etlik Zubeyde Hanim Women’s Health Teaching and Research Hospital, Gynecologic Oncology Department, Ankara, Turkey.
EM gunsukimyon@gmail.com
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:359–386. , DOI 10. 1002/ijc.29210
Bigelow B, Vekshtein V, Demopoulos RI, 1983, Endometrial carcinoma, stage II: route and extent of spread to the cervix. Obstet Gynecol 62:363–366
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Tambouret R, Clement PB, Young RH, 2003, Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix: a manifestation of stage IIb endometrial carcinoma liable to bemisinterpreted as an independent carcinoma or a benign lesion. Am J Surg Pathol 27:1080–1088
Fanning J, Alvarez PM, Tsukada Y, Piver MS, 1991, Prognostic significance of the extent of cervical involvement by endometrial cancer. Gynecol Oncol 40:46–47
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Taskin S, Ortac F, Kahraman K, Goc G, Oztuna D, Gungor M, 2013, Cervical stromal involvement can predict survival in advanced endometrial carcinoma: a review of 67 patients. Int J Clin Oncol 18:105–109. , DOI 10.1007/s10147-011-0351-y
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1431
EP 1436
DI 10.1007/s12253-018-0498-1
PG 6
ER
PT J
AU Yu, D
Cheng, J
Xue, K
Zhao, X
Wen, L
Xu, Ch
AF Yu, Dan
Cheng, Jinzhang
Xue, Kai
Zhao, Xue
Wen, Lianji
Xu, Chengbi
TI Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PDL-1; TAMs; Laryngeal squamous cell carcinoma; Immunosuppression
ID PDL-1; TAMs; Laryngeal squamous cell carcinoma; Immunosuppression
AB To study the expression of programmed death-ligand 1 (PD-L1), and its effects on CD8+ tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in human laryngeal squamous cell carcinoma. Sixty-nine patients with laryngeal carcinoma and 10 with vocal cord leukoplakia received tumor resection at Neck Surgery Department in the Second Affiliation Hospital of Jilin University (Changchun, Jilin) from Jan. 2010 to Dec. 2015. The expressions of PD-L1, CD8, CD16 and CD206 in laryngeal carcinoma, paracancerous and vocal cord leukoplakia tissues were detected with immunohistochemistry. The associations between PD-L1 expression and clinicopathologic features, expression of TAMs and CD8+ T cell infiltration were analyzed. Expression of PD-L1 is significantly higher in laryngeal carcinoma than in paracancerous or leukoplakia tissue. The expression of PD-L1 is closely associated with stage of laryngeal cancer, histological differentiation and neck lymphatic metastasis. PD-L1 expression is negatively correlated with the number of CD8+ TILs and CD16+ cells (M1 type TAMs), while is positively associated with CD206+ (M2 type TAMs). PD-L1 is highly expressed in the laryngeal cancer with the tumor microenvironment immunosuppression.
C1 [Yu, Dan] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
[Cheng, Jinzhang] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
[Xue, Kai] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
[Zhao, Xue] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
[Wen, Lianji] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
[Xu, Chengbi] Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, No. 218 Ziqiang Street, 130041 Changchun, China.
RP Xu, Ch (reprint author), Jilin University, The Second Hospital, Department of Otolaryngology Head and Neck Surgery, 130041 Changchun, China.
EM xuchengbi@163.com
CR Ferris RL, Whiteside TL, Ferrone S, 2006, Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res 12(13):3890–3895
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1437
EP 1443
DI 10.1007/s12253-018-0501-x
PG 7
ER
PT J
AU Foj, L
Filella, X
AF Foj, Laura
Filella, Xavier
TI Identification of Potential miRNAs Biomarkers for High-Grade Prostate Cancer by Integrated Bioinformatics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miRNAs; Bioinformatics analysis; Differentially expressed genes; Protein–protein interaction network; Prostate cancer
ID miRNAs; Bioinformatics analysis; Differentially expressed genes; Protein–protein interaction network; Prostate cancer
AB The increasing number of datasets available in the GEO database offers a new approach to identify new miRNAs related to PCa. The aim of our study was to suggest a miRNA signature for the detection of high-grade PCa (Gleason score ≥ 7) using bioinformatics tools. Three mRNA datasets (GSE26022, GSE30521, GSE46602) were selected to identify the differentially expressed genes (DEGs) in high-grade PCa. Furthermore, two miRNA datasets (GSE45604, GSE46738) were analyzed to select the differentially expressed miRNAs (DEMs). Functional and pathway enrichment analysis was performed using DAVID and a protein-protein interaction network (PPI) was constructed through STRING. Besides, miRNAs which regulate hub genes were predicted using microRNA.org. A total of 973 DEGs were identified after the analyses of the mRNA datasets, enriched in key mechanisms underlying PCa development. Furthermore, we identified 10 hub genes (EGFR, VEGFA, IGF1, PIK3R1, CD44, ITGB4, ANXA1, BCL2, LPAR3, LPAR1). The most significant KEGG Pathway was PI3K-Akt signaling pathway, involved in cell proliferation and survival. Moreover, we identified 30 common miRNAs between significant DEMs and the predicted hub gene regulators. Twelve of these miRNAs (miR-1, −365, −132, −195, −133a, −133b, −200c, −339, −222, −21, −221, −708) regulate two or more hub genes identified in our study. We suggested a signature including these 12 miRNAs for high-grade PCa detection. These miRNAs have been associated with aggressive PCa, poor survival and resistance to treatment in the last years.
C1 [Foj, Laura] SYNLAB Group, Labco DiagnosticsBarcelona, Catalonia, Spain.
[Filella, Xavier] Hospital Clinic, IDIBAPS, Department of Biochemistry and Molecular Genetics (CDB), C/ Villarroel, 170, 08036 Barcelona, Catalonia, Spain.
RP Filella, X (reprint author), Hospital Clinic, IDIBAPS, Department of Biochemistry and Molecular Genetics (CDB), 08036 Barcelona, Spain.
EM xfilella@clinic.cat
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1445
EP 1456
DI 10.1007/s12253-018-0508-3
PG 12
ER
PT J
AU Chmelarova, M
Baranova, I
Ruszova, E
Laco, J
Hrochova, K
Dvorakova, E
Palicka, V
AF Chmelarova, Marcela
Baranova, Ivana
Ruszova, Ema
Laco, Jan
Hrochova, Katerina
Dvorakova, Eva
Palicka, Vladimir
TI Importance of Cadherins Methylation in Ovarian Cancer: a Next Generation Sequencing Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Methylation; Cadherins; Ovarian cancer; Epigenetics; Next generation sequencing
ID Methylation; Cadherins; Ovarian cancer; Epigenetics; Next generation sequencing
AB Epigenetic aberrations are well known to play an important role in carcinogenesis, and also have a great potential to serve as biomarkers in many types of cancers, including ovarian cancer in which sensitive and specific biomarkers and detection methods are critically needed. The aim of this study was to investigate methylation of cadherin genes CDH10, CDH13 and CDH18 in ovarian cancer tissue by comparison with control tissue. The study group consisted of 38 patients with ovarian cancer and 25 control patients. For detection of epigenetic events we used next generation sequencing, the most important data were confirmed using high-resolution melting analysis and real-time PCR. We observed significantly higher methylation in CDH13, sporadic methylation in CDH10 and loss of methylation in CDH18 in the ovarian cancer group compared with the control group. These observations suggest that changes in methylation of cadherin genes may be one of the major mechanisms associated with ovarian cancer progression. In addition, because of the high frequency of methylation of the CDH13 gene in the early stages of ovarian cancer, the analyzed CpG sites might be good targets for next study of potential ovarian cancer screening biomarkers.
C1 [Chmelarova, Marcela] Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Institute for Clinical Biochemistry and DiagnosticsHradec Kralove, Czech Republic.
[Baranova, Ivana] Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Institute for Clinical Biochemistry and DiagnosticsHradec Kralove, Czech Republic.
[Ruszova, Ema] University Hospital Hradec Kralove, Department of Clinical GeneticsHradec Kralove, Czech Republic.
[Laco, Jan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Hrochova, Katerina] Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Institute for Clinical Biochemistry and DiagnosticsHradec Kralove, Czech Republic.
[Dvorakova, Eva] Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Department of Obstetrics and GynecologyHradec Kralove, Czech Republic.
[Palicka, Vladimir] Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Institute for Clinical Biochemistry and DiagnosticsHradec Kralove, Czech Republic.
RP Baranova, I (reprint author), Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Institute for Clinical Biochemistry and Diagnostics, Hradec Kralove, Czech Republic.
EM ivana.baranova@fnhk.cz
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1457
EP 1465
DI 10.1007/s12253-018-0500-y
PG 9
ER
PT J
AU Ghazi-Khanloosani, M
Bandegi, RA
Kokhaei, P
Barati, M
Pakdel, A
AF Ghazi-Khanloosani, Mousa
Bandegi, Reza Ahmad
Kokhaei, Parviz
Barati, Mehdi
Pakdel, Abbas
TI CRP and LOX-1: a Mechanism for Increasing the Tumorigenic Potential of Colorectal Cancer Carcinoma Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Carcinoembryonic antigen; Matrix metalloproteinase; C-reactive protein; Oxidized lowdensity lipoprotein; LOX-1 receptor; Tumorigenic potential
ID Carcinoembryonic antigen; Matrix metalloproteinase; C-reactive protein; Oxidized lowdensity lipoprotein; LOX-1 receptor; Tumorigenic potential
AB Chronic inflammation and dyslipidemia are associated with an increase in the incidence of colorectal cancer (CRC). Serum Creactive protein (CRP) and oxidized low-density lipoprotein (oxLDL), as Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) ligands, increase during inflammation and dyslipidemia, respectively. To evaluate the effects of CRP on the expression of important genes involved in the development of CRC, the CRC cell line, LS174T, was treated with the commercial CRP. Based on the Real-time PCR data, in the presence of CRP, LOX-1, CEA, MMP1, and MMP2 mRNA expression significantly increased, compared to the control group. Moreover, in the presence of CRP, secretion, and expression of CEA in the cell lysate and conditioned media increased in a concentration-dependent manner. The results of flow cytometry showed that expression of LOX-1 receptors at the cell surface increased significantly in the presence of 10 mg/L of CRP. However, inhibition of LOX-1 receptors with a specific monoclonal antibody reduced the effects of CRP on protein/mRNA expression. In conclusion, Increased CRP level, can potentially elevate the expression of important genes in CRC by stimulating LOX-1 receptors.
C1 [Ghazi-Khanloosani, Mousa] Semnan University of Medical Sciences, Faculty of Medicine, Department of BiochemistrySemnan, Iran.
[Bandegi, Reza Ahmad] Semnan University of Medical Sciences, Faculty of Medicine, Department of BiochemistrySemnan, Iran.
[Kokhaei, Parviz] Semnan University of Medical Sciences, Cancer Research Center and Department of ImmunologySemnan, Iran.
[Barati, Mehdi] Semnan University of Medical Sciences, Cancer Research Center and Department of ImmunologySemnan, Iran.
[Pakdel, Abbas] Semnan University of Medical Sciences, Faculty of Medicine, Department of BiochemistrySemnan, Iran.
RP Pakdel, A (reprint author), Semnan University of Medical Sciences, Faculty of Medicine, Department of Biochemistry, Semnan, Iran.
EM pakdel@semums.ac.ir
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1467
EP 1475
DI 10.1007/s12253-018-0507-4
PG 9
ER
PT J
AU Zajkowska, M
Lubowicka, E
Fiedorowicz, W
Szmitkowski, M
Jamiolkowski, J
Lawicki, S
AF Zajkowska, Monika
Lubowicka, Emilia
Fiedorowicz, Wojciech
Szmitkowski, Maciej
Jamiolkowski, Jacek
Lawicki, Slawomir
TI Human Plasma Levels of VEGF-A, VEGF-C, VEGF-D, their Soluble Receptor - VEGFR-2 and Applicability of these Parameters as Tumor Markers in the Diagnostics of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VEGF family members; Diagnostic utility; AUC; ROC
ID VEGF family members; Diagnostic utility; AUC; ROC
AB VEGF family members are important factors in promoting angio- and lymphangiogenesis. The aim of this study was to investigate concentrations, diagnostic utility and power of VEGF-A, VEGF-C, VEGF-D and VEGFR-2 in comparison to CA15–3 in breast cancer (BC) patients. The study included 120 BC patients and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of tested parameters were determined by ELISA, CA15–3 by CMIA. Concentrations of all parameters showed statistical significance when compared BC patients to controls. VEGF-D showed the highest SE (82.50%) in total BC group. Highest SP and PPV in total BC group showed VEGF-A(76.67%;84.78%,respectively), but lower than CA15–3. Highest NPV showed VEGF-C(52.33%), but it was lower than CA15–3. VEGF-C was also the best parameter which had statistically significant AUC in total cancer group (0.7672), but also stages I(0.7684) and II(0.7772). In the total group of BC almost all tested parameters showed statistically significant AUC, but a maximum range was obtained for the combination of VEGF-C + CA15–3(0.8476). The combined analysis of tested parameters and CA15–3 resulted in increase in SE and AUC values, which provides hope for developing a new panel of biomarkers that may be used in the diagnosis of BC in the future.
C1 [Zajkowska, Monika] Medical University of Bialystok, Department of Biochemical Diagnostics, Waszyngtona 15A, 15-269 Bialystok, Poland.
[Lubowicka, Emilia] Medical University of Bialystok, Department of Esthetic Medicine, 15-267 Bialystok, Poland.
[Fiedorowicz, Wojciech] Maria Sklodowska-Curie Oncology Center, Department of Oncological Surgery, 15-001 Bialystok, Poland.
[Szmitkowski, Maciej] Medical University of Bialystok, Department of Biochemical Diagnostics, Waszyngtona 15A, 15-269 Bialystok, Poland.
[Jamiolkowski, Jacek] Medical University of Bialystok, Department of Population Medicine and Civilization Diseases Prevention, 15-269 Bialystok, Poland.
[Lawicki, Slawomir] Medical University of Bialystok, Department of Biochemical Diagnostics, Waszyngtona 15A, 15-269 Bialystok, Poland.
RP Lawicki, S (reprint author), Medical University of Bialystok, Department of Biochemical Diagnostics, 15-269 Bialystok, Poland.
EM slawicki@umb.edu.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1477
EP 1486
DI 10.1007/s12253-018-0527-0
PG 10
ER
PT J
AU Liu, H
Wei, Sh
Zhang, L
Yuan, Ch
Duan, Y
Qingwei, W
AF Liu, Hong
Wei, Shufang
Zhang, Lei
Yuan, Chenxi
Duan, Yuanyuan
Qingwei, Wang
TI Secreted Phosphoprotein 1 Promotes the Development of Small Cell Lung Cancer Cells by Inhibiting Autophagy and Apoptosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SPP1; Small cell lung cancer cells; Autophagy; Apoptosis
ID SPP1; Small cell lung cancer cells; Autophagy; Apoptosis
AB This study aimed to investigate the expression of secreted phosphoprotein 1 (SPP1) on lung cancer cells and explore its underlying mechanism on autophagy and apoptosis which effect the development of lung cancer cells. GSE19804 related to lung cancer cells was screened from Gene Expression Omnibus (GEO) database, and we screened the 47 pairs of differential expressed mRNAs in lung cancer cells and adjacent tissues using microarray analysis. The expression of the core gene SPP1 was detected by qRT-PCR and western-blot. The transfection efficiency of lung cancer cells was detected by qRT-PCR and the expression of transfected group was tested by western-blot. Cell proliferation after transfection was tested by MTT assay and plate cloning experiment. The apoptosis rate of each transfection group was detected by flow cytometry.We use western-blot to test protein expression of autophagy-related proteins Beclin-1, LC3-I, LC3-II and p62 of each transfected group. Through analysis of GSE19804,the heat map showed SPP1 was the highest expressed in tumor tissues. qRT-PCR and western-blot detected SPP1 expression in lung cancer tissues was higher than that in normal adjacent tissues and was significantly increased in lung cancer cell lines. After transfection with pcDNA3.1-SPP1 (p-SPP1 group), siRNA1-SPP1 (siRNA1 group) and siRNA2- SPP1 (siRNA2 group), showed different expression of SPP1. Up-regulation of SPP1 enhanced cell viability and promoted tumor cell proliferation, while knockdown of SPP1 inhibited tumor cell proliferation. From the results of apoptosis rate, SPP1 inhibited the tumor cell apoptosis. However, in normal lung cell, SPP1 had no effect on cell proliferation and apoptosis. And to test autophagy-related proteins, we found that overexpression of SPP1 inhibited autophagy. High expression of SPP1 inhibited autophagy and apoptosis to promote the development of small cell lung cancer cells.
C1 [Liu, Hong] Qilu Hospital of Shandong University, Cancer Research Center, No. 107 Cultural West Road, 250012 Jinan, Shandong, China.
[Wei, Shufang] Qilu Hospital of Shandong University, No.2 Comprehensive Department, 250012 Jinan, Shandong, China.
[Zhang, Lei] Taian City Central Hospital, Department of Thoracic Surgery, 271000 Taian, Shandong, China.
[Yuan, Chenxi] Qilu Hospital of Shandong University, Cancer Research Center, No. 107 Cultural West Road, 250012 Jinan, Shandong, China.
[Duan, Yuanyuan] Qilu Hospital of Shandong University, Cancer Research Center, No. 107 Cultural West Road, 250012 Jinan, Shandong, China.
[Qingwei, Wang] Qilu Hospital of Shandong University, Cancer Research Center, No. 107 Cultural West Road, 250012 Jinan, Shandong, China.
RP Qingwei, W (reprint author), Qilu Hospital of Shandong University, Cancer Research Center, 250012 Jinan, China.
EM xjsnxwj@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1487
EP 1495
DI 10.1007/s12253-018-0504-7
PG 9
ER
PT J
AU Huang, HF
Fan, XR
Ji, ZG
AF Huang, Hou-Feng
Fan, Xin-Rong
Ji, Zhi-Gang
TI The Effectiveness of Sorafenib over Other Targeted Agents in the Second-Line Treatment of Metastatic Renal Cell Carcinoma: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sorafenib; Metastatic renal cell carcinoma; Second-line therapy; Meta-analysis
ID Sorafenib; Metastatic renal cell carcinoma; Second-line therapy; Meta-analysis
AB The aim of the study was to perform a meta-analysis to compare the therapeutic effects and adverse events (AEs) of sorafenib in second-line treatments of metastatic renal cell carcinoma (mRCC). We searched online electronic databases: Pubmed, Embase, Cochrane library updated on November 2017.Trials of the effectiveness of sorafenib in second-line treatments of advanced RCC were included, of which the main outcomes were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and grade 3/4 AE. Other TAs significantly reduced the risk of PFS compared to sorafenib with respect to second-line treatment (HR = 0.74; 95% CI, 0.65–0.83; p < 0.00001). No significant differences were, however, found in patients in terms of the ORR (HR = 1.82; 95% CI, 0.98–3.35; p = 0.06). Frequencies of the most common toxicities were overall similar and adverse events differed only in sensitivity analysis in rash with exclusion of other TAs (HR = 0.16; 95% CI, 0.05–0.52; p = 0.002). Overall survival was not debated between groups. In patients with mRCC, second-line sorafenib is associated with similar ORR as other target agents. While, sorafenib did not demonstrate a PFS advantage compared with other target agents, suggests sorafenib may not benefit patients with mRCC. Tolerability due to toxicities is similar compared sorafenib with other target agents. Further characterization of the RCC oncogenic pathway, and the ongoing clinical trials should help optimize the treatment option for second-line therapy of advanced renal cell carcinoma.
C1 [Huang, Hou-Feng] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, No.1 Shuaifuyuan, Dongcheng District, 100730 Beijing, China.
[Fan, Xin-Rong] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, No.1 Shuaifuyuan, Dongcheng District, 100730 Beijing, China.
[Ji, Zhi-Gang] Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, No.1 Shuaifuyuan, Dongcheng District, 100730 Beijing, China.
RP Ji, ZG (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Department of Urology, 100730 Beijing, China.
EM jzhgpumch@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1497
EP 1503
DI 10.1007/s12253-018-0516-3
PG 7
ER
PT J
AU Sipos, F
Kiss, LA
Constantinovits, M
Tulassay, Zs
Muzes, Gy
AF Sipos, Ferenc
Kiss, L Anna
Constantinovits, Miklos
Tulassay, Zsolt
Muzes, Gyorgyi
TI Modified Genomic Self-DNA Influences In Vitro Survival of HT29 Tumor Cells via TLR9- and Autophagy Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HT29; Colon cancer; TLR9; Autophagy; Colonosphere; Self-DNA
ID HT29; Colon cancer; TLR9; Autophagy; Colonosphere; Self-DNA
AB In relation of immunobiology, the consequence of the crosstalk between TLR9-signaling and autophagy is poorly documented in HT29 cancer cells. To assess the TLR9-mediated biologic effects ofmodified self-DNA sequences on cell kinetics and autophagy response HT29 cells were incubated separately with intact genomic (g), hypermethylated (m), fragmented (f), and hypermethylated/fragmented (m/f) self-DNAs. Cell viability, apoptosis, cell proliferation, colonosphere-formation were determined. Moreover, the relation of TLR9-signaling to autophagy response was assayed by real-time RT-PCR, immunocytochemistry and transmission electron microscopy (TEM). After incubation with g-, m-, and m/f-DNAs cell viability and proliferation decreased, while apoptosis increased. F-DNA treatment resulted in an increase of cell survival.Methylation of self-DNA resulted in decrease of TLR9 expression, while it did not influence the positive effect of DNA fragmentation on MyD88 and TRAF6 overexpression, and TNFα downregulation. Fragmentation of DNA abrogated the positive effect of methylation on IRAK2, NFκB and IL-8 mRNA upregulations. In case of the autophagy genes and proteins, g- and f-DNAs caused significant upregulation of Beclin1, Atg16L1, and LC3B. According to TEM analyses, autophagy was present in each group of tumor cells, but to a varying degree. Incubation with m-DNA suppressed tumor cell survival by inducing features of apoptotic cell death, and activated mitophagy. F-DNA treatment enhanced cell survival, and activated macroautophagy and lipophagy. Colonospheres were only present after m-DNA incubation. Our data provided evidence for a close existing interplay between TLR9-signaling and the autophagy response with remarkable influences on cell survival in HT29 cells subjected to modified self-DNA treatments.
C1 [Sipos, Ferenc] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Kiss, L Anna] Semmelweis University, 1st Department of Anatomy, 1094 Budapest, Hungary.
[Constantinovits, Miklos] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Tulassay, Zsolt] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
[Muzes, Gyorgyi] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi street 46, 1088 Budapest, Hungary.
RP Sipos, F (reprint author), Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
EM dr.siposf@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1505
EP 1517
DI 10.1007/s12253-018-0544-z
PG 13
ER
PT J
AU Kowalewski, A
Szylberg,
Tyloch, J
Antosik, P
Neska-Dlugosz, I
Frackowski,
Tyloch, D
Purpurowicz, P
Grzanka, D
AF Kowalewski, Adam
Szylberg, Lukasz
Tyloch, Janusz
Antosik, Paulina
Neska-Dlugosz, Izabela
Frackowski, Lukasz
Tyloch, Dominik
Purpurowicz, Piotr
Grzanka, Dariusz
TI Caspase 3 as a Novel Marker to Distinguish Chromophobe Renal Cell Carcinoma from Oncocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chromophobe; ChRCC; Oncocytoma; Caspase 3; CASP3; Cyclin D1; p16; Survivin; CD138; Ki-67
ID Chromophobe; ChRCC; Oncocytoma; Caspase 3; CASP3; Cyclin D1; p16; Survivin; CD138; Ki-67
AB Despite advances in our understanding of the biology of chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO), the differential diagnosis among these tumors remains one of the most problematic in renal pathology. Today, CK7 is the most recommended marker to distinguish these entities, however it appears insufficiently accurate by itself. This study aimed to find an easily accessible IHC stain that might out-compete CK7 in this field. Expressions of CK7, cyclin D1, p16, survivin, CD138, Ki-67 and caspase 3 (CASP3) were analyzed in a total of 27 cases (20 ROs and 7 ChRCCs). Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a higher percentage of the total ChRCCs stained positive for CK7 (67% vs. 22%, respectively) and CASP3 (86% vs. 25%) (P < 0.005). The differences in staining with cyclin D1, p16, survivin, CD138 and Ki-67 turned out to be statistically insignificant in differentiating ChRCC from RO. CASP3 is a promising marker in distinguishing ChRCC from RO and may represent an alternative for CK7. Cyclin D1, p16, survivin, CD138 and Ki-67 cannot be used to distinguish these neoplasms.
C1 [Kowalewski, Adam] Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, ul. Sklodowskiej-Curie Str. 9, 85-094 Bydgoszcz, Poland.
[Szylberg, Lukasz] Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, ul. Sklodowskiej-Curie Str. 9, 85-094 Bydgoszcz, Poland.
[Tyloch, Janusz] Nicolaus Copernicus University, Department of General and Oncologic UrologyBydgoszcz, Poland.
[Antosik, Paulina] Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, ul. Sklodowskiej-Curie Str. 9, 85-094 Bydgoszcz, Poland.
[Neska-Dlugosz, Izabela] Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, ul. Sklodowskiej-Curie Str. 9, 85-094 Bydgoszcz, Poland.
[Frackowski, Lukasz] Nicolaus Copernicus University, Department of General and Oncologic UrologyBydgoszcz, Poland.
[Tyloch, Dominik] Nicolaus Copernicus University, Department of General and Oncologic UrologyBydgoszcz, Poland.
[Purpurowicz, Piotr] Nicolaus Copernicus University, Department of General and Oncologic UrologyBydgoszcz, Poland.
[Grzanka, Dariusz] Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, ul. Sklodowskiej-Curie Str. 9, 85-094 Bydgoszcz, Poland.
RP Kowalewski, A (reprint author), Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, 85-094 Bydgoszcz, Poland.
EM kowalewskiresearch@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1519
EP 1524
DI 10.1007/s12253-018-0548-8
PG 6
ER
PT J
AU Sun, G
Meng, J
Duan, H
Zhang, D
Tang, Y
AF Sun, Gongping
Meng, Jin
Duan, He
Zhang, Dewei
Tang, Yuanxin
TI Diagnostic Assessment of septin9 DNA Methylation for Colorectal Cancer Using Blood Detection: A Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SEPT9 methylation; Colorectal cancer; Positive likelihood ratio; Negative likelihood ratio; Summary receiver operating characteristic
ID SEPT9 methylation; Colorectal cancer; Positive likelihood ratio; Negative likelihood ratio; Summary receiver operating characteristic
AB This meta-analysis aimed to assess the diagnostic efficiency of blood-based septin 9 (SEPT9) methylation assay for the detection of colorectal cancer (CRC). Studies were searched in the Springer, Wiley, Cochrane Library, PubMed, Ovid, Embase, Web of Science, China BioMedicine,Wanfang and China National Knowledge Infrastructure databases until July 2017. Methodological quality assessment was performed based on the guidelines of the Quality Assessment of Diagnostic Accuracy Studies. According to 1/3 and 2/3 algorithms, the meta-analyses for the diagnostic effect of SEPT9 in CRC were compared with healthy subjects and subjects with polyps, adenoma, and non-CRC, respectively. The random effects model was applied and publication bias was evaluated. The included 29 studies comprised 10,486 subjects (3202 patients with CRC and 7284 controls). In comparison with healthy subjects, the pooled sensitivity with 95% confidence intervals (CIs) of SEPT9 methylation for the diagnosis of CRC was 0.74 (95% CI: 0.61–0.84) in the 1/3 algorithm group, whereas the specificity was 0.96 (95% CI: 0.95–0.97) in the 2/3 algorithm group. Additionally, positive likelihood ratio was less than 10 and negative likelihood ratio more than 0.1 in the 2/3 algorithm group for patients with CRC vs. polyps and adenoma. The P value of Deeks’ funnel plot was 0.36, suggesting that there was no publication bias. SEPT9 methylation can be used to diagnose CRC in healthy individuals under the 2/3 algorithm. The determination of SEPT9 methylation does not distinguish well between CRC and polyps or adenoma.
C1 [Sun, Gongping] China Medical University, The 4th Affiliated Hospital, Department of Surgery, No. 4 Chongshan Road, 110032 Shenyang, China.
[Meng, Jin] China Medical University, Shengjing Hospital, No. 9 North of Nanjing Street, Heping District, 110000 Shenyang, China.
[Duan, He] China Medical University, The 4th Affiliated Hospital, Department of Surgery, No. 4 Chongshan Road, 110032 Shenyang, China.
[Zhang, Dewei] China Medical University, The 4th Affiliated Hospital, Department of Surgery, No. 4 Chongshan Road, 110032 Shenyang, China.
[Tang, Yuanxin] China Medical University, The 4th Affiliated Hospital, Department of Surgery, No. 4 Chongshan Road, 110032 Shenyang, China.
RP Zhang, D (reprint author), China Medical University, The 4th Affiliated Hospital, Department of Surgery, 110032 Shenyang, China.
EM zhdeweizh@sina.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1525
EP 1534
DI 10.1007/s12253-018-0559-5
PG 10
ER
PT J
AU Allameh, A
Moazeni-Roodi, A
Harirchi, I
Ravanshad, M
Motiee-Langroudi, M
Garajei, A
Hamidavi, A
Mesbah-Namin, AS
AF Allameh, Abdolamir
Moazeni-Roodi, Abdolkarim
Harirchi, Iraj
Ravanshad, Mehrdad
Motiee-Langroudi, Maziar
Garajei, Ata
Hamidavi, Azin
Mesbah-Namin, Alireza Seyed
TI Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE OSCC; HPV; Smoking; P16 promoter methylation; P16 gene expression; Iran
ID OSCC; HPV; Smoking; P16 promoter methylation; P16 gene expression; Iran
AB The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold; p = 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and downregulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.
C1 [Allameh, Abdolamir] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, Iran.
[Moazeni-Roodi, Abdolkarim] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, Iran.
[Harirchi, Iraj] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Ravanshad, Mehrdad] Tarbiat Modares University, Faculty of Medical Sciences, Department of Medical VirologyTehran, Iran.
[Motiee-Langroudi, Maziar] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Garajei, Ata] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Hamidavi, Azin] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, Iran.
[Mesbah-Namin, Alireza Seyed] Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical BiochemistryTehran, Iran.
RP Allameh, A (reprint author), Tarbiat Modares University, Faculty of Medical Sciences, Department of Clinical Biochemistry, Tehran, Iran.
EM allameha@modares.ac.ir
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1535
EP 1543
DI 10.1007/s12253-018-0542-1
PG 9
ER
PT J
AU Zhang, L
Huang, Y
Ling, J
Zhuo, W
Yu, Z
Luo, Y
Zhu, Y
AF Zhang, Liang
Huang, Yi
Ling, JunJun
Zhuo, Wenlei
Yu, Zhen
Luo, Yunbo
Zhu, Yi
TI Is Integrin Subunit Alpha 2 Expression a Prognostic Factor for Liver Carcinoma? A Validation Experiment Based on Bioinformatics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Liver carcinoma; ITGA2; Tissue microarray; Immunohistochemistry; Prognosis
ID Liver carcinoma; ITGA2; Tissue microarray; Immunohistochemistry; Prognosis
AB ITGA2 (Integrin alpha-2) has been detected to be over-expressed in a number of cancers and has been suggested to be involved in cell adhesion and cell-surface mediated signaling. Our previous study using bioinformatic analyses has shown that ITGA2 might be a key gene being involved in the Cadmium-induced malignant transformation of liver cells. In the present study, we firstly aimed to learn the possible functions of ITGA2 via bioinformatics analysis, and then test its expression and clinical significance in liver carcinoma specimens through laboratory experiments. Gene ontology (GO) and pathway enrichment analysis, as well as protein-protein interaction (PPI) analysis has been conducted in Genecards. Then, a tissue microarray containing 90 cases of liver cancer and 90 paired adjacent non-cancerous samples was used for detection of ITGA2 expression by immunohistochemistry assay. Consequently, ITGA2 may be enriched in pathways regarding cell adhesion and migration. PPI analysis suggests that ITGA1, ITGB2, FLT4, LAMB1 and AGRN may have a close relationship with ITGA2. No association between ITGA2 expression and clinical parameters was observed. However, the data showed that ITGA2 might be an independent prognostic factor for liver cancer patients. In conclusion, the data suggest that ITGA2 over-expression might be a potential unfavorable prognostic factor and a potential therapeutic target for liver carcinoma.
C1 [Zhang, Liang] China Agricultural University, College of food science and nutritional engineeringBeijing, China.
[Huang, Yi] Affiliated hospital of Guizhou Medical University, Department of Internal MedicineGuiyang, China.
[Ling, JunJun] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
[Zhuo, Wenlei] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
[Yu, Zhen] China Agricultural University, College of food science and nutritional engineeringBeijing, China.
[Luo, Yunbo] China Agricultural University, College of food science and nutritional engineeringBeijing, China.
[Zhu, Yi] China Agricultural University, College of food science and nutritional engineeringBeijing, China.
RP Zhu, Y (reprint author), China Agricultural University, College of food science and nutritional engineering, Beijing, China.
EM zhuyi@cau.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1545
EP 1552
DI 10.1007/s12253-018-0551-0
PG 8
ER
PT J
AU Xie, B
Nie, Sh
Hu, G
Xiong, L
Hu, F
Li, M
Peng, T
Nie, J
He, Y
AF Xie, Biao
Nie, Shaolin
Hu, Gui
Xiong, Li
Hu, Fan
Li, Mei
Peng, Tianshu
Nie, Jing
He, Yongheng
TI The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LPS; NF-κB; Colorectal cancer; Klotho
ID LPS; NF-κB; Colorectal cancer; Klotho
AB Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-κB p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-κB inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-κB p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4/NF-κB signal pathway.
C1 [Xie, Biao] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department One of Anorectal Surgery, 139 Renmin Road, 410005 Changsha, Hunan, China.
[Nie, Shaolin] Hunan Province Tumor Hospital, Department of Colorectal Surgery, 410013 Changsha, Hunan, China.
[Hu, Gui] The Third Xiangya Hospital, Central South University, Department of Gastrointestinal Surgery, 410013 Changsha, Hunan, China.
[Xiong, Li] Central South University, the Second Xiangya Hospital, Department of Hepatobiliary Surgery, 410008 Changsha, Hunan, China.
[Hu, Fan] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department One of Anorectal Surgery, 139 Renmin Road, 410005 Changsha, Hunan, China.
[Li, Mei] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department One of Anorectal Surgery, 139 Renmin Road, 410005 Changsha, Hunan, China.
[Peng, Tianshu] Hunan Slack King Laboratory Animal Co., Ltd., 4100125 Changsha, Hunan, China.
[Nie, Jing] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department Four of Anorectal Surgery, 410005 Changsha, Hunan, China.
[He, Yongheng] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department One of Anorectal Surgery, 139 Renmin Road, 410005 Changsha, Hunan, China.
RP He, Y (reprint author), The Second Affiliated Hospital of Hunan University of Chinese Medicine, Department One of Anorectal Surgery, 410005 Changsha, China.
EM heyongheng1964@163.com
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Zhang G, Ghosh S, 2000, Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through toll-like receptors. J Endotoxin Res 6:453–457
Zhou X, Wang X, 2015, Klotho: a novel biomarker for cancer. J Cancer Res Clin Oncol 141:961–969
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Xie B, Zhou J, Shu G, Liu DC, Zhou J, Chen J, Yuan L, 2013, Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer. Cancer Cell Int 13:18
Shu G, Xie B, Ren F, Liu DC, Zhou J, Li Q, Chen J, Yuan L, Zhou J, 2013, Restoration of klotho expression induces apoptosis and autophagy in hepatocellular carcinoma cells. Cell Oncol, Dordr, 36: 121–129
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1553
EP 1565
DI 10.1007/s12253-018-0493-6
PG 13
ER
PT J
AU Luo, Y
He, Y
Ye, X
Song, J
Wang, Q
Li, Y
Xie, X
AF Luo, Yongyun
He, Yaqin
Ye, Xiaoping
Song, Jianjun
Wang, Qi
Li, Yukui
Xie, Xiaoliang
TI High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HOTAIRM1; Pancreatic ductal adenocarcinoma; Proliferation; Migration
ID HOTAIRM1; Pancreatic ductal adenocarcinoma; Proliferation; Migration
AB Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy. Long noncoding RNA (LncRNA) HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been shown to play important roles in the progression of several type cancers. However, the exact role of HOTAIRM1 in PDAC development remains largely unknown. This study aims to evaluate the potential function of HOTAIRM1 in the development and progress of PDAC. HOTAIRM1 expression was measured by RT-qPCR in forty seven paired human PDAC tissues and five PDAC cell lines. SW1990 and PANC-1 cells were transfected with siHOTAIRM1 to achieve HOTAIRM1 silence. MTT assay and colony formation assay were used to detect the effect of HOTAIRM1 knockdown on cell proliferation. The impact of HOTAIRM1 silence on cell cycle and apoptosis was assessed by flow cytometry assay. Transwell migration assay was performed to explore the influence of HOTAIRM1 downregulation on the migratory potential of PDAC cells.Western blot assay was applied to determine the expression changes of cell cycle, apoptosis, and migration-related genes before and after downregulating HOTAIRM1. HOTAIRM1 expression was abnormally upregulated in PDAC tissues and cells when compared with the control samples, and was positively associated with the expression of KRAS gene mutation. In vitro functional experiments, HOTAIRM1 expression was significantly downregulated by transfection with siHOTAIRM1 in SW1990 and PANC cell lines. HOTAIRM1 knockdown attenuated cell proliferation by inducing cell cycle arrest at G0/G1 phase, promoted cell apoptosis, and inhibited cell migration in PDAC cells by regulating related-genes expression. In conclusion, HOTAIRM1 plays a critical role in PDAC progression, which may be a novel diagnostic and rational therapeutic target for the treatment of pancreatic ductal adenocarcinoma.
C1 [Luo, Yongyun] Ningxia Medical University, General Hospital, Department of Hepatobiliary Surgery, 750004 Yinchuan, China.
[He, Yaqin] Ningxia Medical University, General Hospital, Surgery Laboratory, 804 South Shengli Street, 750004 Yinchuan, China.
[Ye, Xiaoping] Ningxia Medical University, General Hospital, Department of Colorectal Surgery, 804 South Shengli Street, 750004 Yinchuan, China.
[Song, Jianjun] Ningxia Medical University, General Hospital, Department of Hepatobiliary Surgery, 750004 Yinchuan, China.
[Wang, Qi] Ningxia Medical University, General Hospital, Department of Hepatobiliary Surgery, 750004 Yinchuan, China.
[Li, Yukui] Ningxia Medical University, General Hospital, Surgery Laboratory, 804 South Shengli Street, 750004 Yinchuan, China.
[Xie, Xiaoliang] Ningxia Medical University, General Hospital, Department of Colorectal Surgery, 804 South Shengli Street, 750004 Yinchuan, China.
RP Li, Y (reprint author), Ningxia Medical University, General Hospital, Surgery Laboratory, 750004 Yinchuan, China.
EM zaimo571@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1567
EP 1577
DI 10.1007/s12253-018-00570-4
PG 11
ER
PT J
AU Lalosevic, SM
Coric, MV
Pekmezovic, DT
Simic, PT
Ercegovac, PM
Markovic, PA
Krivokapic, VZ
AF Lalosevic, Lj. Stojkovic Milica
Coric, M Vesna
Pekmezovic, D Tatjana
Simic, P Tatjana
Ercegovac, S. Pljesa Marija
Markovic, R. Pavlovic Aleksandra
Krivokapic, V Zoran
TI Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Glutathione-S transferases; GST polymorphism; Carcinogenesis; Colorectal cancer development
ID Colorectal cancer; Glutathione-S transferases; GST polymorphism; Carcinogenesis; Colorectal cancer development
AB Glutathione-S transferases (GSTs) are xenobiotic-conjugation enzymes involved in the detoxification process of heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, widely recognized risk factors of colorectal cancer (CRC) development. Polymorphism in GSTs often leads to alteration or complete lack of enzyme activity, which might have an effect on CRC carcinogenesis. Aim of this study was to investigate GST gene variants as risk factors in patients with CRC. A total of 523 CRC patients administered for surgical resection and 400 matched controls were included. Deletion polymorphism of GSTs M1 and T1 was investigated by polymerase chain reaction. Single nucleotide polymorphism of GSTA1 and P1 was investigated by restriction fragment length polymorphism method. The association between GST genotype and risk of CRC development was found in carriers of GSTT1-null and GSTP1-variant genotypes individually (p = 0.050 and p = 0.016, respectively). Furthermore, statistically significant association was found when combination of GSTP1-variant genotype with any of other three common GST genotypes was analyzed with respect to CRC susceptibility. Additionally, patients with combined GSTM1-null/GSTT1-null/GSTA1 low-activity/GSTP1-variant genotype showed 2.71-fold increased risk of developing CRC (p = 0.037). This study supports hypothesis that GST polymorphisms might have an important role in the process of the CRC development. Additionally, GSTM1-null/ GSTT1-null/ GSTA1 low-activity/ GSTP1-variant genotype could be combination of GST genotypes whose carriers are more prone to CRC development.
C1 [Lalosevic, Lj. Stojkovic Milica] Clinical center of Serbia, Clinic of gastroenterology and hepatology, 11000 Belgrade, Serbia.
[Coric, M Vesna] Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, 11000 Belgrade, Serbia.
[Pekmezovic, D Tatjana] University of Belgrade, Faculty of Medicine, 11000 Belgrade, Serbia.
[Simic, P Tatjana] Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, 11000 Belgrade, Serbia.
[Ercegovac, S. Pljesa Marija] Belgrade University, Faculty of Pharmacy, Institute of Medical Biochemistry, 11000 Belgrade, Serbia.
[Markovic, R. Pavlovic Aleksandra] Clinical center of Serbia, Clinic of gastroenterology and hepatology, 11000 Belgrade, Serbia.
[Krivokapic, V Zoran] University of Belgrade, Faculty of Medicine, 11000 Belgrade, Serbia.
RP Krivokapic, VZ (reprint author), University of Belgrade, Faculty of Medicine, 11000 Belgrade, Serbia.
EM jagodica85@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1579
EP 1587
DI 10.1007/s12253-019-00589-1
PG 9
ER
PT J
AU Eiro, N
Carrion, FJ
Cid, S
Andicoechea, A
Garcia-Muniz, LJ
Gonzalez, OL
Vizoso, JF
AF Eiro, Noemi
Carrion, Francisco Juan
Cid, Sandra
Andicoechea, Alejandro
Garcia-Muniz, Luis Jose
Gonzalez, O Luis
Vizoso, J Francisco
TI Toll-Like Receptor 4 and Matrix Metalloproteases 11 and 13 as Predictors of Tumor Recurrence and Survival in Stage II Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prognostic factor; Stage II colorectal cancer; Survival; TLR4; MMP11; MMP13
ID Prognostic factor; Stage II colorectal cancer; Survival; TLR4; MMP11; MMP13
AB Current clinical-pathologic stratification factors do not allow clear identification of high-risk stage II colorectal cancer (CRC) patients. Therefore, the identification of additional prognostic markers is desirable. Toll-like receptor (TLR)-4 is activated during tumorigenesis and matrix metalloproteases (MMPs) are involved in invasion and metastasis.We aimed to evaluate the expression and clinical relevance of TLR4, MMP11 and MMP13 for patients with stage II CRC. Immunohistochemistry was used to study the expression of TLR4, MMP11 and MMP13 in 96 patients with stage II CRC. We measured the global expression and the expression by different cell types (tumor cells, cancer-associated fibroblasts (CAFs) and mononuclear inflammatory cells (MICs)). The potential relationship between expressions of factors and different prognostic variables were evaluated. Our results show significant relationships between either TLR4 expression by tumor cells and MMP11 expression by CAFs and high risk of tumor recurrence. In addition, the concurrence of age ≥ 75 years and the non-expression of MMP11 by CAFs identify a subgroup of patients with a good prognosis. Our results show that TLR4 expression by tumor cells and MMP11 expression by CAFs may to improve the identification of patients with stage II CRC with a high-risk of relapse.
C1 [Eiro, Noemi] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
[Carrion, Francisco Juan] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
[Cid, Sandra] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
[Andicoechea, Alejandro] Fundacion Hospital de Jove, Servicio de Cirugia General, 33290 Gijon, Asturias, Spain.
[Garcia-Muniz, Luis Jose] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
[Gonzalez, O Luis] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
[Vizoso, J Francisco] Fundacion Hospital de Jove, Unidad de Investigacion, Avda. Eduardo Castro 161, 33290 Gijon, Asturias, Spain.
RP Vizoso, JF (reprint author), Fundacion Hospital de Jove, Unidad de Investigacion, 33290 Gijon, Spain.
EM investigacion@hospitaldejove.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1589
EP 1597
DI 10.1007/s12253-019-00611-6
PG 9
ER
PT J
AU Yaghobi Joybari, A
Azadeh, P
Babaei, S
Hosseini Kamal, F
AF Yaghobi Joybari, Ali
Azadeh, Payam
Babaei, Siamak
Hosseini Kamal, Farnaz
TI Comparison of Capecitabine (Xeloda) vs. Combination of Capecitabine and Oxaliplatin (XELOX) as Neoadjuvant CRT for Locally Advanced Rectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemotherapy; Capecitabine; Oxaliplatin; Rectal cancer
ID Chemotherapy; Capecitabine; Oxaliplatin; Rectal cancer
AB We decided to compare pathologic complete response (pCR) and disease-free survival (DFS) in rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy (CRT) with capecitabine plus oxaliplatin (XELOX) or capecitabine (Xeloda). In this study, patients with non-metastatic locally advanced rectal cancer (tumor stages of T2, T3, or T4) with or without lymph node involvement were retrospectively included. Patients received concomitant radiation (50.4–54 Gy external beam radiation in 28 to 30 fractions) and neoadjuvant therapy as either Xeloda (capecitabine, 2500 mg/m2 concomitantly with radiation therapy) (42patients) or XELOX [(oxaliplatin (50 mg/m2 intravenously once a week for five weeks) and capecitabine)] (72 patients). Surgery was done eight weeks after CRT. The endpoints were pCR (defined as no evidence of viable tumoral cells) and DFS (the interval from the initial treatment to the first tumor recurrence). Rectal sphincter preservation via low-anterior resection (LAR) was achieved in 73.8% of Xeloda group which was similar to XELOX group (70.8%), P = 0.61. pCR was documented in 11 (26.9%) of Xeloda group and 26 patients (36.1%) of XELOX group (P = 0.27). Tumor recurrence was recorded in 97 patients (85.1%). Mean (±SD) DFS was 52.13 (±31.92) months (median = 48 months). Mean (95% CI) DFS was 129.42 (110.19 to 148.64) in Xeloda group vs. 122.77 (110.72 to 134.83) in XELOX group (P = 0.74). Addition of oxaliplatin to capecitabine as neoadjuvant CRT for locally advanced rectal cancer did not result in improved pCR or better DFS.
C1 [Yaghobi Joybari, Ali] Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Radiation Oncology, Arabi Ave., Velenjak, 1983963113 Tehran, Iran.
[Azadeh, Payam] Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Radiation Oncology, Arabi Ave., Velenjak, 1983963113 Tehran, Iran.
[Babaei, Siamak] Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Radiation Oncology, Arabi Ave., Velenjak, 1983963113 Tehran, Iran.
[Hosseini Kamal, Farnaz] Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Radiation Oncology, Arabi Ave., Velenjak, 1983963113 Tehran, Iran.
RP Azadeh, P (reprint author), Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Radiation Oncology, 1983963113 Tehran, Iran.
EM payazad@yahoo.com
CR Lorimer PD, Motz BM, Kirks RC, Boselli DM,Walsh KK, Prabhu RS, Hill JS, Salo JC, 2017, Pathologic complete response rates after neoadjuvant treatment in rectal Cancer: An analysis of the National Cancer Database. Ann Surg Oncol 24(8):2095–2103
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1599
EP 1605
DI 10.1007/s12253-019-00587-3
PG 7
ER
PT J
AU Smolarz, B
Michalska, MM
Samulak, D
Romanowicz, H
Wojcik, L
AF Smolarz, Beata
Michalska, M Magdalena
Samulak, Dariusz
Romanowicz, Hanna
Wojcik, Luiza
TI Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; DNA repair; Polymorphism; Gene
ID Ovarian cancer; DNA repair; Polymorphism; Gene
AB Ovarian cancer is one of the most common types of cancer in women. The repair system via homologous recombination repairs double-strand breaks (DSB) of DNA, which are the most mortal for cell, out of all DNA damages. The genes, which encode the double-strand break repairing proteins, are highly polymorphic and, taking into account the significance of the repaired defects for cancer development, it seems important to learn the role of the polymorphisms in ovarian cancer development. The aim of the study was to determine the relationship between DNA repair genes via homologous recombination (HR) and modulation of the risk of ovarian cancer. The following polymorphisms were analysed: XRCC3-Thr241Met (rs861539), XRCC2–41657C/T (rs718282), XRCC2-Arg188His (rs3218536), BRCA1-Q356R (rs1799950) and RAD51–135 G/C (rs1801320). The study group included 600 patients with ovarian cancer and 600 healthy controls. The PCR-RFLP (PCR-based restriction fragment length polymorphism) technique was applied for polymorphism analysis. Allele XRCC3-241Met (OR 0.85, 95% CI 0.72–0.99, p < 0.045), XRCC2-41657 T (OR 1.67, 95% CI 1.42–1.96, p < .0001), BRCA1-356R (OR 1.61; % CI 1.37–1.90, p < .0001) and RAD51–135C (OR 5.16; 95% CI 4.29–6.20, p < .0001) strongly correlated with the neoplastic disease. No relationship was observed between the studied polymorphisms and the cancer progression stage according to FIGO classification. The results indicate that polymorphisms of DNA repair genes via homologous recombination may be associated with the incidence of ovarian cancer. Further research on larger groups is warranted to determine the influence of above-mentioned genetic variants on ovarian cancer risk.
C1 [Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Michalska, M Magdalena] Regional Hospital in Kalisz, Department of Obstetrics and GynaecologyKalisz, Poland.
[Samulak, Dariusz] Regional Hospital in Kalisz, Department of Obstetrics and GynaecologyKalisz, Poland.
[Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
[Wojcik, Luiza] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, Rzgowska 281/289, 93-338 Lodz, Poland.
RP Smolarz, B (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular Genetics, 93-338 Lodz, Poland.
EM smolbea@wp.pl
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Hemminki K, Forsti A, Bermejo JL, 2005, Single nucleotide polymorphisms, SNPs, are inherited from parents and they measure heritable events. J Carcinog 4:2
Erichsen HC, Chanock SJ, 2004, SNPs in cancer research and treatment. Br J Cancer 90:747–751
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Michalska MM, Samulak D, Bienkiewicz J, Romanowicz H, Smolarz B, 2015, Association between -41657C/T single nucleotide polymorphism of DNA repair gene XRCC2 and endometrial cancer risk in Polish women. Pol J Pathol 66:67–71
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Michalska MM, Samulak D, Romanowicz H, Smolarz B, 2015, Single Nucleotide Polymorphisms, SNPs, of RAD51-G172T and XRCC2-41657C/T Homologous Recombination Repair Genes and the Risk of Triple- Negative Breast Cancer in PolishWomen. Pathol Oncol Res 21:935–940
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1607
EP 1614
DI 10.1007/s12253-019-00604-5
PG 8
ER
PT J
AU Varga, G
Nagy, Zs
Demeter, J
Kosztolanyi, Sz
Szomor,
Hussain, A
Deak, B
Schneider, T
Plander, M
Szendrei, T
Varoczy, L
Illes,
Batai,
Peto, M
Mikala, G
AF Varga, Gergely
Nagy, Zsolt
Demeter, Judit
Kosztolanyi, Szabolcs
Szomor, Arpad
Hussain, Alizadeh
Deak, Beata
Schneider, Tamas
Plander, Mark
Szendrei, Tamas
Varoczy, Laszlo
Illes, Arpad
Batai, Arpad
Peto, Monika
Mikala, Gabor
TI Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiple myeloma; Relapsed; Ixazomib; Named patient program
ID Multiple myeloma; Relapsed; Ixazomib; Named patient program
AB Ixazomib-Revlimid-Dexamethasone is an all-oral treatment protocol for multiple myeloma with a manageable tolerability profile which was available through a named patient program for Hungarian patients from December 2015 to April 2017.We analyzed the clinical characteristics and survival of 77 patients treated at 7 centers within this program. The majority of patients responded, we found complete response in 9, very good partial response in 8, partial response in 32, minor response or stable disease in 13 and progressive disease in 11 patients. Progression free survival was 11.4 months. There was a trend of longer progression free survival in those with 1 vs. >1 prior treatment, with equally good effectivity in standard risk and high risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. There were 5 fatalities: 3 infections and 2 pulmonary embolisms. Our real word data support the use of Ixazomib-Revlimid-Dexamethasone as a highly effective and well tolerated oral treatment protocol for relapsed myeloma.
C1 [Varga, Gergely] Semmelweis University, 3rd Department of Internal Medicine, Kutvolgyi ut 4, H-1125 Budapest, Hungary.
[Nagy, Zsolt] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Demeter, Judit] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Kosztolanyi, Szabolcs] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Szomor, Arpad] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Hussain, Alizadeh] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Deak, Beata] National Institute of OncologyBudapest, Hungary.
[Schneider, Tamas] National Institute of OncologyBudapest, Hungary.
[Plander, Mark] Vas County Markusovszky HospitalSzombathely, Hungary.
[Szendrei, Tamas] Vas County Markusovszky HospitalSzombathely, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Batai, Arpad] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Peto, Monika] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Varga, G (reprint author), Semmelweis University, 3rd Department of Internal Medicine, H-1125 Budapest, Hungary.
EM vargager@gmail.com
CR Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, di Bacco A, Hui AM, van de Velde H, Richardson PG, 2016, Oral Ixazomib, Lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 374(17):1621–1634
Mateos MV, Masszi T, Grzasko N, Hansson M, Sandhu I, Pour L, Viterbo L, Jackson SR, Stoppa AM, Gimsing P, Hamadani M, Borsaru G, Berg D, Lin J, di Bacco A, van de Velde H, Richardson PG, Moreau P, 2017, Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/ refractory multiple myeloma in TOURMALINE-MM1. Haematologica 102(10):1767–1775
Al-Salama ZT, Garnock-Jones KP, Scott LJ, 2017, Ixazomib: a review in relapsed and/or refractory multiple myeloma. Target Oncol 12(4):535–542
Terpos E, Maouche N, Minarik J et al, 2017, "Real world" data on the efficacy and safety of Ixazomib in combination with Lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: a combined study from the Greek, Czech and UK databases. Blood, 130(Suppl 1), 3087
Ziff M, Cheesman S, Kyriakou C, 2017, Real world use of ixazomib with lenalidomide and dexamethasone for patients with relapsed and relapsed refractory multiple myeloma. EHA 2017 Abstract 1975
Terpos E, Katodritou E, Kotsopoulou M, 2017)BReal world^ data on the efficacy and safety of ixazomib in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: a study of the Greek myeloma study group. EHA 2017 Abstract 1249
Durie BG, Harousseau JL, Miguel JS et al, 2006, International uniform response criteria for multiple myeloma. Leukemia 20: 1467–1473
Leleu X, Masszi T, Bahlis NJ, Viterbo L, Baker B, Gimsing P, Maisnar V, Samoilova O, Rosinol L, Langer C, Song K, Izumi T, Cleeland C, Berg D, Lin HM, Zhu Y, Skacel T, Moreau P, Richardson PG, 2018, Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomiblenalidomide- dexamethasone versus placebo-lenalidomidedexamethasone in relapsed/refractory multiple myeloma. Am J Hematol [Epub ahead of print] 93:985–993
Armoiry X, Connock M, Tsertsvadze A, Cummins E, Melendez- Torres GJ, Royle P, Clarke A, 2018, Ixazomib for relapsed or refractory multiple myeloma: review from an evidence review group on a NICE single technology appraisal. Pharmacoeconomics [Epub ahead of print] 36:1073–1081
Hari P, Lin HM, Zhu Yet al, 2018, Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma. J Med Econ 29:1–6 [Epub ahead of print]
Avet-Loiseau H, Bahlis NJ, ChngWJ, Masszi T, Viterbo L, Pour L, Ganly P, Palumbo A, Cavo M, Langer C, Pluta A, Nagler A, Kumar S, Ben-Yehuda D, Rajkumar SV, San-Miguel J, Berg D, Lin J, van de Velde H, Esseltine DL, di Bacco A, Moreau P, Richardson PG, 2017, Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood 130(24): 2610–2618
Dimopoulos MA, Kaufman JL,White D, Cook G, Rizzo M, Xu Y, Fahrbach K, Gaudig M, Slavcev M, Dearden L, Lam A, 2018, A comparison of the efficacy of immunomodulatory-containing regimens in relapsed/refractory multiple myeloma: a network metaanalysis. Clin Lymphoma Myeloma Leuk 18(3):163–173
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1615
EP 1620
DI 10.1007/s12253-019-00607-2
PG 6
ER
PT J
AU Liu, Z
Yang, M
Wang, S
Chen, Hp
Guan, X
Zhao, Zx
Jiang, Z
Quan, Jch
Yang, Rk
Wang, Xsh
AF Liu, Zheng
Yang, Ming
Wang, Song
Chen, Hai-peng
Guan, Xu
Zhao, Zhi-xun
Jiang, Zheng
Quan, Ji-chuan
Yang, Run-kun
Wang, Xi-shan
TI GGN Promotes Tumorigenesis by Regulating Proliferation and Apoptosis in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Gametogenetin (GGN); Proliferation; Apoptosis
ID Colorectal cancer; Gametogenetin (GGN); Proliferation; Apoptosis
AB Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. GGN is a germ cell-specific gene, but its function in CRC has been rarely reported to date. The aim of this study was to investigate the potential role of GGN in CRC tumorigenesis. Therefore, in this study, we examined the expression of GGN in CRC cell lines and tissues and its effects on cellular proliferation and apoptosis. We then explored the underlying mechanism. Our results showed that GGN was significantly overexpressed in both CRC cell lines and tissues. Silencing GGN robustly inhibited proliferation of CRC cells, and it also promoted apoptosis of CRC cells.Moreover, knockdown of GGN inhibited the expression of p-Akt in CRC cells. Taken together, these results showed that knockdown of GGN inhibits proliferation and promotes apoptosis of CRC cells through the PI3K/Akt signaling pathway. Our findings revealed for the first time a potential oncogenic role for GGN in CRC progress. This finding may provide a unique perspective on how a germ cell-specific gene might serve as a biomarker, or even as a therapeutic target, for CRC.
C1 [Liu, Zheng] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Yang, Ming] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Wang, Song] The Second Affiliated Hospital of Harbin Medical University, Department of Colorectal Cancer SurgeryHarbin, China.
[Chen, Hai-peng] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Guan, Xu] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Zhao, Zhi-xun] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Jiang, Zheng] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Quan, Ji-chuan] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
[Yang, Run-kun] The Second Affiliated Hospital of Harbin Medical University, Department of Colorectal Cancer SurgeryHarbin, China.
[Wang, Xi-shan] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 17 Panjiayuan Nanli, Chaoyang Dist., 100021 Beijing, China.
RP Wang, Xsh (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Department of Colorectal Surgery, 100021 Beijing, China.
EM wxshan1208@126.com
CR Siegel RL, Miller KD, Jemal A, 2018, Cancer statistics, 2018. CA Cancer J Clin 68:7–30
ChenW, Zheng R, Baade PD et al, 2016, Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132
Kuipers EJ, Grady WM, Lieberman D et al, 2015, Colorectal cancer. Nat Rev Dis Primers 1:15065
Fakih MG, 2015, Metastatic colorectal cancer: current state and future directions. J Clin Oncol 33:1809–1824
Brenner H, KloorM, Pox CP, 2014, Colorectal cancer. Lancet 383: 1490–1502
Colussi D, Brandi G, Bazzoli F, Ricciardiello L, 2013, Molecular pathways involved in colorectal cancer: implications for disease behavior and prevention. Int J Mol Sci 14:16365–16385
Johnston PG, 2014, Identification of clinically relevant molecular subtypes in colorectal cancer: the dawning of a new era. Oncologist 19:568–573
Lu B, Bishop CE, 2003, Mouse GGN1 and GGN3, two germ cellspecific proteins from the single gene GGN, interact with mouse POG and play a role in spermatogenesis. J Biol Chem 278:16289–16296
Jamsai D, Sarraj MA, Merriner DJ, Drummond AE, Jones KT, McLachlan RI, O’Bryan MK, 2011, GGN1 in the testis and ovary and its variance within the Australian fertile and infertile male population. Int J Androl 34:624–632
WangW, LiC,Chen Y, Teng L, CaoY,XuY, Pan H, AnR, 2018, Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis. Gene 652:7–15
Lan ZJ, Hu Y, Zhang S, Li X, Zhou H, Ding J, Klinge CM, Radde BN, Cooney AJ, Zhang J, Lei Z, 2016, GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor α activity in breast cancer cells. Breast Cancer Res Treat 158:263–276
Yin F, Liu L, Liu X et al, 2014, Downregulation of tumor suppressor gene ribonuclease T2 and gametogenetin binding protein 2 is associated with drug resistance in ovarian cancer. Oncol Rep 32: 362–372
Tariq K, Ghias K, 2016, Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol Med 13:120–135
Okugawa Y, Grady WM, Goel A, 2015, Epigenetic alterations in colorectal Cancer: emerging biomarkers. Gastroenterology 149: 1204–1225.e12
Chen A, Li J, Song L, Ji C, Boing M, Chen J, Brand-Saberi B, 2017, GGNBP2 is necessary for testis morphology and sperm development. Sci Rep 7:2998
Zhao Q, Zhou Y, Cao Z, Zhu H, Huang P, Lu B, 2005, Germ-cell specific protein gametogenetin protein 2, GGN2), expression in the testis, and association with intracellular membrane. Mol Reprod Dev 72:31–39
Stoian M, State N, Stoica V, Radulian G, 2014, Apoptosis in colorectal cancer. J Med Life 7:160–164
Galluzzi L, Lopez-Soto A, Kumar S, Kroemer G, 2016, Caspases connect cell-death signaling to organismal homeostasis. Immunity 44:221–231
Malinowsky K, Nitsche U, Janssen KP, Bader FG, Spath C, Drecoll E, Keller G, Hofler H, Slotta-Huspenina J, Becker KF, 2014, Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer. Br J Cancer 110:2081–2089
Danielsen SA, Eide PW, Nesbakken A et al, 2015, Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim Biophys Acta 1855:104–121
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1621
EP 1626
DI 10.1007/s12253-019-00595-3
PG 6
ER
PT J
AU Esfandi, F
Ghafouri-Fard, S
Kholghi Oskooei, V
Taheri, M
AF Esfandi, Farbod
Ghafouri-Fard, Soudeh
Kholghi Oskooei, Vahid
Taheri, Mohammad
TI β-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BACE1; BACE1-AS; Gastric cancer
ID BACE1; BACE1-AS; Gastric cancer
AB β-secretase (BACE1) and its naturally occurring anti-sense RNA (BACE1-AS) have established role in the pathologic process leading to Alzheimer’s disease. Their possible implication in the neoangiogenesis suggests that they might be involved in the tumorigenesis events as well. In the present study, we compared transcript levels of these genes in 30 gastric cancer samples and their adjacent non-cancerous tissues (ANCTs) to find whether their altered expression might facilitate discrimination of these two sets of samples. Expressions of both genes were associated with site of primary tumor. Both genes were significantly downregulated in tumoral tissues compared with ANCTs. Significant correlations were detected between transcript levels of these genes in both sets of samples. Transcript levels of BACE1 and BACE1-AS had the diagnostic power of 75% based on Receiver operating characteristic curve analysis. The current study provides evidences for contribution of BACE1 and BACE1-AS in gastric cancer evolution and suggests their potential as diagnostic markers.
C1 [Esfandi, Farbod] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Ghafouri-Fard, Soudeh] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Kholghi Oskooei, Vahid] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Taheri, Mohammad] Shahid Beheshti University of Medical Sciences, Urogenital Stem Cell Research CenterTehran, Iran.
RP Taheri, M (reprint author), Shahid Beheshti University of Medical Sciences, Urogenital Stem Cell Research Center, Tehran, Iran.
EM mohammad_823@yahoo.com
CR Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A, DeStrooper B, Saftig P, Birchmeier C, Haass C, 2006, Control of peripheral nerve myelination by the beta-secretase BACE1. Science 314:664–666
John V, 2006, Human beta-secretase, BACE, and BACE inhibitors: progress report. Curr Top Med Chem 6:569–578
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Paris D, Quadros A, Patel N, DelleDonne A, Humphrey J, Mullan M, 2005, Inhibition of angiogenesis and tumor growth by beta and gamma-secretase inhibitors. Eur J Pharmacol 514:1–15
Nienhuser H, Schmidt T, 2018, Angiogenesis and anti-angiogenic therapy in gastric cancer. Int J Mol Sci 19(1):43
Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufenbiel M, Huang LE, SongW(2006, Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci U S A 103:18727–18732
Zhang X, Zhou K,Wang RS, Cui JK, Lipton SA, Liao FF, Xu HX, ZhangYW(2007, Hypoxia-inducible factor 1 alpha, HIF-1 alpha)- mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282:10873–10880
Kitajima Y, Miyazaki K, 2013, The critical impact of HIF-1a on gastric cancer biology. Cancers, Basel, 5:15–26
Urano N, Fujiwara Y, Doki Y, Tsujie M, Yamamoto H, Miyata H, Takiguchi S,Yasuda T,YanoM,MondenM(2006)Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric Cancer 9:44–49
Rossner S, Sastre M, Bourne K, Lichtenthaler SF, 2006, Transcriptional and translational regulation of BACE1 expression–implications for Alzheimer’s disease. Prog Neurobiol 79:95–111
Lange-Dohna C, Zeitschel U, Gaunitz F, Perez-Polo JR, Bigl V, Rossner S, 2003, Cloning and expression of the rat BACE1 promoter. J Neurosci Res 73:73–80
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1627
EP 1633
DI 10.1007/s12253-019-00621-4
PG 7
ER
PT J
AU Miyamura, Y
Kagara, N
Miyake, T
Tanei, T
Naoi, Y
Shimoda, M
Shimazu, K
Kim, JS
Noguchi, Sh
AF Miyamura, Yukiko
Kagara, Naofumi
Miyake, Tomohiro
Tanei, Tomonori
Naoi, Yasuto
Shimoda, Masafumi
Shimazu, Kenzo
Kim, Jin Seung
Noguchi, Shinzaburo
TI Drainage of Tumor-Derived DNA into Sentinel Lymph Nodes in Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating tumor DNA; Sentinel lymph node; PIK3CA mutation; Apoptosis
ID Circulating tumor DNA; Sentinel lymph node; PIK3CA mutation; Apoptosis
AB Circulating tumor DNA (ctDNA) is released from cancer cells by apoptosis or other mechanisms, and as tumor tissue contains both blood and lymphatic vessels, ctDNA can spread to local lymph nodes (LNs). We aimed to detect the tumor-derived free DNA in metastasis-free LNs in patients with breast cancers harboring the PIK3CA-H1047R mutation. One hundred twenty-three patients were evaluated and the PIK3CA-H1047R mutation was assayed in sentinel LNs (SLNs), non-SLNs without metastasis, and serum by digital PCR. The mutant DNA was more frequent in metastasis-free SLNs (21.6%) than in metastasis-free non- SLNs (8.6%; P = 0.038), and patients with mutation-positive SLNs were more likely to be positive for serum mutant DNA. Apoptosis in primary breast tumors was determined by TUNEL assay. The apoptotic index was significantly higher (P = 0.003) in patients with mutation-positive SLNs without metastasis (mean, 1.17%) than those with mutation-negative SLNs without metastasis (mean, 0.79%). It was also significantly higher (P = 0.006) in those with mutation-positive serum (mean, 1.41%) than in those with mutation-negative serum (mean, 0.86%). Furthermore, fragment size of PIK3CA-H1047R mutant DNA in metastatic-free SLN lysate used for the one-step nucleic acid amplification (OSNA) assay was short (<500 bp). These results support the theory that DNA is released from the primary tumor via apoptotic fragmentation. In conclusion, ctDNA is detectable in metastasis-free LNs and significantly more frequent in SLNs from patients with breast tumors harboring a high apoptotic index, consistent with drainage of ctDNA from apoptotic primary tumor cells into SLNs.
C1 [Miyamura, Yukiko] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Kagara, Naofumi] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Miyake, Tomohiro] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Tanei, Tomonori] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Naoi, Yasuto] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Shimoda, Masafumi] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Shimazu, Kenzo] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Kim, Jin Seung] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
[Noguchi, Shinzaburo] Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 2-2-E10, Yamadaoka, Suita, 565-0871 Osaka, Japan.
RP Kagara, N (reprint author), Osaka University, Graduate School of Medicine, Department of Breast and Endocrine Surgery, 565-0871 Osaka, Japan.
EM kagaran@onsurg.med.osaka-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1635
EP 1643
DI 10.1007/s12253-019-00618-z
PG 9
ER
PT J
AU Liu, B
Li, X
Liu, F
Li, F
Wei, Sh
Liu, J
Lv, Y
AF Liu, Bo
Li, Xiujuan
Liu, Fengxi
Li, Fengyu
Wei, Shuxia
Liu, Junchao
Lv, Yang
TI Expression and Significance of TRIM 28 in Squamous Carcinoma of Esophagus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; TRIM28; Immunohistochemistry; Western blot; Immunofluorescence; Overall survival
ID Esophageal squamous cell carcinoma; TRIM28; Immunohistochemistry; Western blot; Immunofluorescence; Overall survival
AB Tripartite motif-containing protein 28 (TRIM28) has been proved to accelerate cell proliferation and metastasis in a variety of human cancers. However, the role of TRIM28 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, to compare the biological effect and significance of TRIM28 expression in ESCC, immunohistochemistry (streptavidin-perosidase, S-P) method was used firstly to examine the expression of TRIM28 in 136 cases of ESCC, 35 cases of high grade intraepithelial neoplasia (HGIN), 29 cases of low grade intraepithelial neoplasia (LGIN) and 37 cases of normal esophageal epithelium (NEE). Then the associations of TRIM28 expression with clinicopathological data and overall survival (OS) were also analyzed. Western blot was performed to evaluate TRIM28 protein in a total of 20 matched human ESCC and NEE tissues. Moreover, the localization of TRIM28 protein in ESCC and NEE tissues was also detected by immunofluorescence. TRIM28 protein was mainly distributed in the nucleus of ESCC. The expression of TRIM28 increased progressively from NEE to LGIN, to HGIN, and to ESCC, and it was also related to invasive depth, pTNM stage and lymph node metastasis in ESCC (P < 0.05). The results of western blot and immunofluorescence all showed that the relative expression of TRIM28 protein was markedly upregulated in ESCC compared with the NEE tissues (P < 0.01). However, prognostic analysis showed that TRIM28 may not be a prognostic factor of patients with ESCC. In conclusion, the overexpression of TRIM28 may play an important role for development and metastasis in ESCC.
C1 [Liu, Bo] First Affiliated Hospital of Hebei North University, Department of Pathology, 075000 Zhangjiakou, Hebei, China.
[Li, Xiujuan] Hebei North University, Department of Histology and Embryology, 11 Zuanshi South Road, 075000 Zhangjiakou, Hebei, China.
[Liu, Fengxi] Hebei North University, Department of Histology and Embryology, 11 Zuanshi South Road, 075000 Zhangjiakou, Hebei, China.
[Li, Fengyu] No.251 Hospital of the Chinese People’s Liberation Army, Department of Oncology, 075000 Zhangjiakou, Hebei, China.
[Wei, Shuxia] No.251 Hospital of the Chinese People’s Liberation Army, Department of Oncology, 075000 Zhangjiakou, Hebei, China.
[Liu, Junchao] First Affiliated Hospital of Hebei North University, Department of Pathology, 075000 Zhangjiakou, Hebei, China.
[Lv, Yang] Hebei North University, Department of Histology and Embryology, 11 Zuanshi South Road, 075000 Zhangjiakou, Hebei, China.
RP Lv, Y (reprint author), Hebei North University, Department of Histology and Embryology, 075000 Zhangjiakou, China.
EM hbbfxy_lvyang@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1645
EP 1652
DI 10.1007/s12253-018-0558-6
PG 8
ER
PT J
AU Wang, Y
Li, X
Zhang, J
Liu, Q
Gao, P
Li, D
Zhang, Sh
Liu, J
AF Wang, Yue
Li, Xiaorui
Zhang, Jiahao
Liu, Qiang
Gao, Peng
Li, Di
Zhang, Shijie
Liu, Ju
TI CIZ1 Expression Is Upregulated in Hemangioma of the Tongue
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CIZ1; Hemangioma; Cell proliferation; Migration
ID CIZ1; Hemangioma; Cell proliferation; Migration
AB Hemangioma is a vascular neoplasm and one of the most common benign tumors. The pathogenesis of hemangioma has not been fully understood. CIZ1 (Cip1-interacting zinc finger protein 1) is a nuclear protein and the binding partner of p21. Dysregulation of CIZ1 expression has been reported in various types of cancerous tissues. In this study, we examined CIZ1 expression in hemangioma of the tongue and explored its function in vascular endothelial cells, the proliferative cell type in hemangioma. Immunohistochemistry showed that CIZ1 was highly expressed in hemangioma of the tongue while its expression is minimal in the normal tongue tissues. In vitro, knockdown of CIZ1 expression by shRNA transfection significantly reduced the proliferation and migration of human umbilical vein endothelium cells (HUVECs), suggesting a positive role of CIZ1 in endothelial cell proliferation and migration. Therefore, CIZ1 might involve in pathogenesis of hemangioma of the tongue by regulation of endothelial cell functions.
C1 [Wang, Yue] Shandong University, School of Dentistry, Department of OrthodonticsJinan, China.
[Li, Xiaorui] Shandong University, Shandong Provincial Qianfoshan Hospital, Medical Research CenterJinan, China.
[Zhang, Jiahao] Shandong University, School of Dentistry, Department of OrthodonticsJinan, China.
[Liu, Qiang] Shandong University, Shandong Provincial Qianfoshan Hospital, Medical Research CenterJinan, China.
[Gao, Peng] Shandong University, Shandong Provincial Qianfoshan Hospital, Medical Research CenterJinan, China.
[Li, Di] Pennsylvania State University, Eberly College of Sciences, 16801 University Park, PA, USA.
[Zhang, Shijie] Qilu Hospital of Shandong University, Department of StomatologyJinan, China.
[Liu, Ju] Shandong University, Shandong Provincial Qianfoshan Hospital, Medical Research CenterJinan, China.
RP Liu, J (reprint author), Shandong University, Shandong Provincial Qianfoshan Hospital, Medical Research Center, Jinan, China.
EM ju.liu@sdu.edu.cn
CR Correa PH, Nunes LC, Johann AC, Aguiar MC, Gomez RS,Mesquita RA(2007, Prevalence of oral hemangioma, vascular malformation and varix in a Brazilian population. Braz Oral Res 21(1):40–45
Pranitha V, Puppala N, Deshmukh SN, Jagadesh B, Anuradha S, 2014, Cavernous hemangioma of tongue: management of two cases. J Clin Diagn Res 8(10):ZD15–ZD17
El-Raggal NM, El-Farrash RA, Saad AA, Attia EAS, Saafan HA, Shaaban IS, 2018, Circulating levels of vascular endothelial growth factor and basic fibroblastic growth factor in infantile hemangioma versus vascular malformations. Clin Appl Thromb Hemost 24(4): 663–668
El-Hashemite N, Walker V, Kwiatkowski DJ, 2005, Estrogen enhances whereas tamoxifen retards development of Tsc mouse liver hemangioma: a tumor related to renal Angiomyolipoma and pulmonary lymphangioleiomyomatosis. Cancer Res 65(6):2474–2481
Liu Q, Niu N,WadaY, Liu J, 2016, The role of Cdkn1A-interacting zinc finger protein 1, CIZ1, in DNA replication and pathophysiology. Int J Mol Sci 17(2):212
Wang DQ, Wang K, Yan DW, Liu J, Wang B, Li MX, Wang XW, Liu J, Peng ZH, Li GX, Yu ZH, 2014, Ciz1 is a novel predictor of survival in human colon cancer. Exp Biol Med, Maywood, 239(7): 862–870
Zhou X, Liu Q,Wada Y, Liao L, Liu J, 2017, CDKN1Ainteracting zinc finger protein 1 is a novel biomarker for lung squamous cell carcinoma. Oncol Lett 5(1):183–188
ZhangD,WangY, Dai Y,Wang J,SuoT, PanH,LiuH, ShenS, Liu H, 2015, CIZ1 promoted the growth and migration of gallbladder cancer cells. Tumour Biol 36(4):2583–2591
Reggiani Bonetti L, Boselli F, Lupi M, Bettelli S, Schirosi L, Bigiani N, Sartori G, Rivasi F, 2009, Expression of estrogen receptor in hemangioma of the uterine cervix: reports of three cases and review of the literature. Arch Gynecol Obstet 280(3):469–472
den Hollander P, Rayala SK, Coverley D, Kumar R, 2006, Ciz1, a novel DNA-binding coactivator of the estrogen receptor alpha, confers hypersensitivity to estrogen action. Cancer Res 66(22):11021– 11029
Mai HM, Zheng JW, Wang YA, Yang XJ, Zhou Q, Qin ZP, Li KL, 2013, CD133 selected stem cells from proliferating infantile hemangioma and establishment of an in vivo mice model of hemangioma. Chin Med J 126(1):88–94
Yu Y, Varughese J, Brown LF, Mulliken JB, Bischoff J, 2001, Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangiomaderived endothelial cells. Am J Pathol 159(6):2271–2280
Ou JM, Yu ZY, Qiu MK, Dai YX, Dong Q, Shen J, Wang XF, Liu YB, Quan ZW, Fei ZW, 2014, Knockdown of VEGFR2 inhibits proliferation and induces apoptosis in hemangioma-derived endothelial cells. Eur J Histochem 58(1):2263
Wu JK, Adepoju O, de Silva D, Baribault K, Boscolo E, Bischoff J, Kitajewski J, 2010, A switch in notch gene expression parallels stem cell to endothelial transition in infantile hemangioma. Angiogenesis 13(1):15–23
Ji Y, Chen S, Li K, Li L, Xu C, Xiang B, 2014, Signaling pathways in the development of infantile hemangioma. J Hematol Oncol 7:13
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1653
EP 1658
DI 10.1007/s12253-018-0495-4
PG 6
ER
PT J
AU Villamanan, L
Alcaraz, E
Pinna, AL
Ruzzene, M
Itarte, E
Arus, C
Plana, M
Candiota, PA
AF Villamanan, Lucia
Alcaraz, Estefania
Pinna, A Lorenzo
Ruzzene, Maria
Itarte, Emilio
Arus, Carles
Plana, Maria
Candiota, Paula Ana
TI Up-Regulation of the Alpha Prime Subunit of Protein Kinase CK2 as a Marker of Fast Proliferation in GL261 Cultured Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cell cycle; GL261 glioma; Cyclin D1; Preclinical brain tumour model; CK2 alpha prime
ID Cell cycle; GL261 glioma; Cyclin D1; Preclinical brain tumour model; CK2 alpha prime
AB Glioblastoma (GB) is the most prevalent malignant primary brain tumor in adults. The preclinical glioblastoma model GL261 is widely used for investigating new therapeutic strategies. GL261 cultured cells are used for assessing preliminary in vitro data for this model although very little is known about the molecular characteristics of this cell line. Protein Kinase CK2 is a pleiotropic serine-threonine kinase and its inhibition may be a promising therapeutic strategy for GB treatment. In our group we follow treatment response with CK2 inhibitors in vivo using the GL261 murine model. For that, it is of our interest to assess the differential expression of α, α’, β CK2 subunits as well as CK2 activity in the GL261 GB model. CK2α’ expression changed along the growth curve of GL261 cells, undergoing downregulation in postconfluent phase cells, whereas CK2α and CK2β expression remained essentially unchanged. Furthermore, a marked decrease in CK2 activity in slowly proliferating postconfluent phase GL261 cells was observed. Finally, CK2α’ expression in orthotopic GL261 tumors was intermediate between CK2α’ expression found in cultured cells in exponentially growing or postconfluent phase, reflecting the heterogeneous nature of GL261 tumours growing in vivo. The results obtained suggest that, in the GL261 cell line, CK2α’ could play a specific role in highly proliferative cells. Also, the decrease in CK2 activity in slowly proliferating GL261 cells could imply a differential susceptibility to subunit-specific CK2 inhibitors in this cell line, although further studies are needed to confirm this hypothesis.
C1 [Villamanan, Lucia] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
[Alcaraz, Estefania] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
[Pinna, A Lorenzo] University of Padova, and CNR Institute of Neurosciences, Department of Biomedical Sciences, via U. Bassi 58B, 35131 Padova, Italy.
[Ruzzene, Maria] University of Padova, and CNR Institute of Neurosciences, Department of Biomedical Sciences, via U. Bassi 58B, 35131 Padova, Italy.
[Itarte, Emilio] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
[Arus, Carles] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
[Plana, Maria] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
[Candiota, Paula Ana] Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Cerdanyola del VallesBarcelona, Spain.
RP Candiota, PA (reprint author), Universitat Autonoma de Barcelona, Departament de Bioquimica i Biologia Molecular, Barcelona, Spain.
EM AnaPaula.Candiota@uab.cat
CR Stupp R,Mason WP, van den BentMJ,WellerM, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E,Mirimanoff RO, 2005, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. , DOI 10.1056/NEJMoa043330
Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna LA, Ruzzene M, 2005, Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ 12(6):668–677. , DOI 10.1038/sj.cdd.4401604
Rowse AL, Gibson SA, Meares GP, Rajbhandari R, Nozell SE, Dees KJ, Hjelmeland AB, McFarland BC, Benveniste EN, 2017, Protein kinase CK2 is important for the function of glioblastoma brain tumor initiating cells. J Neuro-Oncol 132(2):219–229. https:// doi.org/10.1007/s11060-017-2378-z
Stacey DW(2003, Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Current opinion in cell biology 15, 2): 158-163. , DOI 10.1016/S0955-0674(03)00008-5
Ferrer-Font L, Alcaraz E, Plana M, Candiota AP, Itarte E, Arus C, 2016, Protein kinase CK2 content in GL261 mouse glioblastoma. Pathol Oncol Res 22(3):633–637. , DOI 10.1007/s12253- 015-9987-7
Ferrer-Font L, Villamanan L, Arias-Ramos N, Vilardell J, Plana M, Ruzzene M, Pinna LA, Itarte E, Arus C, Candiota AP, 2017, Targeting protein kinase CK2: evaluating CX-4945 potential for GL261 glioblastoma therapy in immunocompetent mice. Pharmaceuticals 10(1). , DOI 10.3390/ph10010024
OrlandiniM, Semplici F, Ferruzzi R, Meggio F, Pinna LA, Oliviero S, 1998, Protein kinaseCK2alpha' is induced by serumas a delayed early gene and cooperates with Ha-ras in fibroblast transformation. J Biol Chem 273, 33):21291–21297. , DOI 10.1074/jbc. 273.33.21291
Ortega-Martorell S, Lisboa PJG, Vellido A, Simoes RV, Pumarola M, Julia-Sape M, Arus C, 2012, Convex Non-Negative Matrix Factorization for Brain Tumor Delimitation from MRSI Data. PLoS One 7, 10):e47824. , DOI 10.1371/journal.pone.0047824
Janeczko M, Orzeszko A, Kazimierczuk Z, Szyszka R, Baier A, 2012, CK2alpha and CK2alpha' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem 47(1):345–350. , DOI 10.1016/ j.ejmech.2011.11.002
Bollacke A, Nienberg C, Borgne ML, Jose J, 2016, Toward selective CK2alpha and CK2alpha' inhibitors: development of a novel wholecell kinase assay by autodisplay of catalytic CK2alpha'. J Pharm Biomed Anal 121:253–260. , DOI 10.1016/j.jpba.2016.01.011
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1659
EP 1663
DI 10.1007/s12253-018-00567-z
PG 5
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI EGFR-TK1-Associated Interstitial Pneumonitis in Nivolumab-Treated Patients with NSCLC: When Is it Worth The Risk?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR OshimaY, Tanimoto T, Yuji K, Tojo A, 2018, EGFR-TKI-associated interstitial pneumonitis inNivolumab-treated patients with non-small cell lung Cancer. JAMA Oncol 4(8):1112–1115
Santabarbara G, Maione P, Rossi A, Palazzolo G, Gridelli C, 2016, Novel immunotherapy in the treatment of advanced non-small cell lung cancer. Expert Rev Clin Pharmacol 9(12):1571–1581
Ahn MJ, Sun JM, Lee SH, Ahn JS, Park K, 2017, EGFR TKI combination with immunotherapy in non-small cell lung cancer. Expert Opin Drug Saf 16(4):465–469
Gettinger S, Hellmann MD, Chow LQM, Borghaei H, Antonia S, Brahmer JR, Goldman JW, Gerber DE et al, 2018, Nivolumab plus erlotinib in patients with EGFR-mutant advanced NSCLC. J Thorac Oncol 13(9):1363–1372
Haratani K, Hayashi H, Tanaka T, Kaneda H, Togashi Y, Sakai K, Hayashi K et al, 2017, Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment. Ann Oncol 28(7):1532–1539
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1665
EP 1666
DI 10.1007/s12253-019-00599-z
PG 2
ER
PT J
AU Li, Xl
Dai, Shd
AF Li, Xiao-li
Dai, Shun-dong
TI Melanotic Schwannoma: Two Cases of Rare Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Li, Xiao-li] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, Liaoning, China.
[Dai, Shun-dong] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of PathologyShenyang, Liaoning, China.
RP Dai, Shd (reprint author), China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, Shenyang, China.
EM sddai@cmu.edu.cn
CR Louis DN, 2007, WHO classification of tumours of the central nervous system[M]. In: International Agency for Research on Cancer
Mahato D, Vivasbuitrago T, Gassie K et al, 2017, Intracranial melanotic schwannomas: a rare variant with unusual adherent features[J]. J Neuro-Oncol:136(1)
Cheng X, Liu J, Le J et al, 2017, Invasive intramedullary melanotic schwannoma: case report and review of the literature[J]. Eur Spine J: 1–6
Torresmora J, Dry S, Li X et al, 2014, Malignant melanotic schwannian tumor: a clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of "melanotic schwannoma".[J]. Am J Surg Pathol 38(1):94–105
Lee JK, Rho YJ, Dong MJ et al, 2017, Diagnostic clue of meningeal melanocytoma: case report and review of literature[J]. Yonsei Med J 58(2):467–470
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1667
EP 1670
DI 10.1007/s12253-018-0417-5
PG 4
ER
PT J
AU Altundag, K
AF Altundag, Kadri
TI Significant Family History of Breast Cancer may Further Increase Risk of Pre-malignant and Malignant Lesions in Specimens from Breast Reduction Surgery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Altundag, Kadri] MKA Breast Cancer Clinic, Tepe Prime, Cankaya, 06800 Ankara, Turkey.
RP Altundag, K (reprint author), MKA Breast Cancer Clinic, 06800 Ankara, Turkey.
EM altundag66@yahoo.com
CR Uson Junior PLS, Callegaro Filho D, Bugano DDG, Geyer FC, de Nigro Corpa MV, Goncalves PDS, Simon SD, Kaliks RA, 2018, Incidental Findings in Reduction Mammoplasty Specimens in Patients with No Prior History of Breast Cancer. An Analysis of 783 Specimens. Pathol Oncol Res 24(1):95–99
Metcalfe KA, Finch A, Poll A, Horsman D, Kim-Sing C, Scott J, Royer R, Sun P, Narod SA, 2009, Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation. Br J Cancer 100(2):421–425
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1671
EP 1671
DI 10.1007/s12253-018-0437-1
PG 1
ER
PT J
AU Raj, Th
Patil, Sh
Sarode, CS
Sarode, SG
AF Raj, A. Thirumal
Patil, Shankargouda
Sarode, C Sachin
Sarode, S Gargi
TI Oral Potentially Malignant Disorder Based Customized Epithelial Dysplasia Grading: a Need of the Hour
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Raj, A. Thirumal] Sri Venkateswara Dental College and Hospital, Department of Oral Pathology and Microbiology, Thalambur, 600130 Chennai, India.
[Patil, Shankargouda] Jazan University, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral PathologyJazan, Saudi Arabia.
[Sarode, C Sachin] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, PimpriPune, India.
[Sarode, S Gargi] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, PimpriPune, India.
RP Raj, Th (reprint author), Sri Venkateswara Dental College and Hospital, Department of Oral Pathology and Microbiology, 600130 Chennai, India.
EM thirumalraj666@gmail.com
CR Gale N, Pilch BZ, Sidransky D, 2005, Epithelial precursor lesions. In: Barnes L, Eveson J, Reichart P, Sidransky D, eds, World Health Organization classification of tumors: pathology and genetics of tumors of the head and neck. IARC Press, Lyon
Reibel J, Gale N, Hille J et al, 2017, Oral potentially malignant disorders and oral epithelial dysplasias. In: El-Naggar AK, Chan JKC, Gradis JR, Takata T, Slootweg PJ, eds, WHO classification of tumours of the head and neck. Tumors of the oral cavity and mobile tongue, 4th edn. IARC Press, Lyon
Warnakulasuriya S, Tilakaratne WM, Ranganathan K, Kuriakose MA, 2018, Report of a consensus meeting of a group of oral and general pathologists in India on the grading of oral epithelial dysplasia. Oral Oncol. , DOI 10.1016/j.oraloncology. 2018.03.018
Muller S, 2017, Update from the 4th edition of the world health organization of head and neck tumors: tumors of the oral cavity and mobile tongue. Head Neck Pathol 11:33–40. , DOI 10. 1007/s12105-017-0794-1
Sarode SC, Chaudhary M, Gadbail A, Tekade S, Patil S, Sarode GS, 2018, Dysplastic features relevant to malignant transformation in the atrophic epithelium of oral submucous fibrosis: a preliminary study. J Oral Pathol Med. , DOI 10.1111/jop.12699
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1673
EP 1674
DI 10.1007/s12253-018-0455-z
PG 2
ER
PT J
AU Son, JH
Kim, SM
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Absence of Promoter Mutation in TBC1D12 Gene in Solid and Hematologic Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Oguchi ME, Noguchi K, Fukuda M, 2017, TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells. PLoS One 12:e0174883
Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G, 2017, Recurrent and functional regulatory mutations in breast cancer. Nature 547:55–60
Heng J, Guo X,WuW,Wang Y, Li G, Chen M, Peng L,Wang S, Dai L, Tang L, Wang J, 2017, Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients. PLoS One 12:e0174022
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2019
VL 25
IS 4
BP 1675
EP 1676
DI 10.1007/s12253-018-0468-7
PG 2
ER
PT J
AU Kopper, L
Timar, J
AF Kopper, Laszlo
Timar, Jozsef
TI 25th Anniversary of Pathology Oncology Research
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Editorial
C1 [Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Kopper, L (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM kopper@korb1.sote.hu
CR Kopper L, 1995, Prologue. Pathol Oncol Res 1:6
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 1
EP 1
DI 10.1007/s12253-020-00795-2
PG 1
ER
PT J
AU Lendvai, G
Szekerczes, T
Illyes, I
Dora, R
Kontsek, E
Gogl, A
Kiss, A
Werling, K
Kovalszky, I
Schaff, Zs
Borka, K
AF Lendvai, Gabor
Szekerczes, Timea
Illyes, Ildiko
Dora, Reka
Kontsek, Endre
Gogl, Aliz
Kiss, Andras
Werling, Klara
Kovalszky, Ilona
Schaff, Zsuzsa
Borka, Katalin
TI Cholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cholangiocarcinoma; Liver cancer; Biliary markers; Stem cells; MicroRNA
ID Cholangiocarcinoma; Liver cancer; Biliary markers; Stem cells; MicroRNA
AB Cholangiocarcinoma (CC) is the second most common tumor of the liver, originating from the biliary system with increasing incidence and mortality worldwide. Several new classifications review the significance of tumor localization, site of origin, proliferation and biomarkers in the intrahepatic, perihilar and distal forms of the lesion. Based on growth pattern mass-forming, periductal-infiltrating, intraductal, undefined and mixed types are differentiated. There are further subclassifications which are applied for the histological features, in particular for intrahepatic CC. Recognition of the precursors and early lesions of CC including biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile ducts (IPNB), biliary mucinous cystic neoplasm (MCNB) and the candidate precursors, such as bile duct adenoma and von Meyenburg complex is of increasing significance. In addition to the previously used biliary markers detected by immunohistochemistry, several new markers have been added to the differentiation of both the benign and malignant lesions, which can be used to aid in the subclassification in association with the outcome of CC. Major aspects of biliary carcinogenesis have been revealed, yet, the exact way of this diverse process is still unclear. The factors contributing to molecular cholangiocarcinogenesis include various risk factors, different anatomical localizations, multiple cellular origins, genetic and epigenetic alterations, tumor microenvironment, heterogeneity and clonal evolution. Driver mutations have been identified, implying that they are optimal candidates for targeted therapy. The most promising therapeutic candidates have entered clinical trials.
C1 [Lendvai, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Illyes, Ildiko] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Dora, Reka] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kontsek, Endre] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Gogl, Aliz] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Werling, Klara] Semmelweis University, 2nd Department of Internal Medicine, H-1085 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Borka, Katalin] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff.zsuzsa@med.semmelweis-univ.hu
CR Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM, Gores GJ, 2014, Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 60(6):1268–1289
Dodson RM, Weiss MJ, Cosgrove D, Herman JM, Kamel I, Anders R, Geschwind JF, Pawlik TM, 2013, Intrahepatic cholangiocarcinoma: management options and emerging therapies. J Am Coll Surg 217(4):736–750 e734
Rizvi S, Gores GJ, 2013, Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 145(6):1215– 1229
Javle M, Bekaii-Saab T, Jain A, Wang Y, Kelley RK, Wang K, Kang HC, Catenacci D, Ali S, Krishnan S, Ahn D, Bocobo AG, Zuo M, Kaseb A, Miller V, Stephens PJ, Meric-BernstamF, Shroff R, Ross J, 2016, Biliary cancer: utility of next-generation sequencing for clinical management. Cancer 122(24):3838–3847
Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H, 2010, Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2(12):419–427
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 3
EP 15
DI 10.1007/s12253-018-0491-8
PG 13
ER
PT J
AU Doma, V
Barbai, T
Beleaua, MA
Kovalszky, I
Raso, E
Timar, J
AF Doma, Viktoria
Barbai, Tamas
Beleaua, M-A
Kovalszky, Ilona
Raso, Erzsebet
Timar, Jozsef
TI KIT Mutation Incidence and Pattern of Melanoma in Central Europe
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Skin melanoma; Mucosal melanoma; KIT mutation and sanger sequencing
ID Skin melanoma; Mucosal melanoma; KIT mutation and sanger sequencing
AB Data on the KIT mutation rate in melanoma in the central European region is missing. Accordingly, in a cohort of 79 BRAF/ NRAS double wild type cutaneous melanoma and 17 mucosal melanoma KIT mutation was assessed by Sanger sequencing of exons 9,11,13,17 and 18. In this cutaneous melanoma cohort KIT mutation frequency was found to be 34/79 (43.04%) with a significantly higher rate in acrolentiginous melanoma (ALM) as compared to UV-induced common variants (20/34, 58.8% versus 14/45, 31.1%, p = 0.014). In the double wild type mucosal melanoma cohort the KIT mutation frequency was found to be comparable (41.2%). The actual frequency of KIT mutation in the original 227 patient cutaneous melanoma cohort was 34/ 227, 14.9%. Exon 11 was the most frequent mutation site (44.7%) followed by exon 9 (21.1%) equally characterizing UV induced common histotypes and ALM tumors. In mucosal melanoma exon 9 was the most frequently involved exon followed by exon 13 and 17. KIT mutation hotspots were identified in exon 9 (c482/491/492), in exon 11 (c559,c572, c570), in exon 13 (c642), in exon 17 (c822) and in exon 18 (c853). The relatively high KIT mutation rate in cutaneous melanoma in this central- European cohort justifies regular testing of this molecular target in this entity, not only in mucosal variants.
C1 [Doma, Viktoria] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Barbai, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Beleaua, M-A] University of Medicine, Department of Pathology, Pharmacy and ScienceTargu-Mures, Romania.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM jtimar@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 17
EP 22
DI 10.1007/s12253-019-00788-w
PG 6
ER
PT J
AU Petovari, G
Danko, T
Krencz, I
Hujber, Z
Rajnai, H
Vetlenyi, E
Raffay, R
Papay, J
Jeney, A
Sebestyen, A
AF Petovari, Gabor
Danko, Titanilla
Krencz, Ildiko
Hujber, Zoltan
Rajnai, Hajnalka
Vetlenyi, Eniko
Raffay, Regina
Papay, Judit
Jeney, Andras
Sebestyen, Anna
TI Inhibition of Metabolic Shift can Decrease Therapy Resistance in Human High-Grade Glioma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Metabolism; Metabolic shift; mTORC2; Combination therapy
ID Glioma; Metabolism; Metabolic shift; mTORC2; Combination therapy
AB The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tumours in central nervous system. The developing resistance against recent therapies and the recurrence rate of GBMs are extremely high. In spite several new ongoing trials, GBM therapies could not significantly increase the survival rate of the patients as significantly. The presence of inter- and intra-tumoral heterogeneity of GBMs arise the problem to find both the pre-existing potential resistant clones and the cellular processes which promote the adaptation mechanisms such as multidrug resistance, stem cell-ness or metabolic alterations, etc. In our work, the in situ metabolic heterogeneity of high-grade human glioblastoma cases were analysed by immunohistochemistry using tissue-microarray. The potential importance of the detected metabolic heterogeneity was tested in three glioma cell lines (grade III-IV) using protein expression analyses (Western blot and WES Simple) and therapeutic drug (temozolomide), metabolic inhibitor treatments (including glutaminase inhibitor) to compare the effects of rapamycin (RAPA) and glutaminase inhibitor combinations in vitro (Alamar Blue and SRB tests). The importance of individual differences and metabolic alterations were observed in mono-therapeutic failures, especially the enhanced Rictor expressions after different monotreatments in correlation to lower sensitivity (temozolomide, doxycycline, etomoxir, BPTES). RAPA combinations with other metabolic inhibitors were the best strategies except for RAPA+glutaminase inhibitor. These observations underline the importance of multi-targeting metabolic pathways. Finally, our data suggest that the detected metabolic heterogeneity (the high mTORC2 complex activity, enhanced expression of Rictor, p-Akt, p-S6, CPT1A, and LDHA enzymes in glioma cases) and the microenvironmental or treatment induced metabolic shift can be potential targets in combination therapy. Therefore, it should be considered to map tissue heterogeneity and alterations with several cellular metabolism markers in biopsy materials after applying recently available or new treatments.
C1 [Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Hujber, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Rajnai, Hajnalka] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Vetlenyi, Eniko] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Raffay, Regina] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Papay, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Jeney, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Sebestyen, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM anna@korb1.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 23
EP 33
DI 10.1007/s12253-019-00677-2
PG 11
ER
PT J
AU Krencz, I
Sebestyen, A
Khoor, A
AF Krencz, Ildiko
Sebestyen, Anna
Khoor, Andras
TI mTOR in Lung Neoplasms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Lung neoplasms; mTORC1; mTORC2; mTOR inhibitors; mTOR signaling
ID Lung neoplasms; mTORC1; mTORC2; mTOR inhibitors; mTOR signaling
AB With the discovery of rapamycin 45 years ago, studies in the mechanistic target of rapamycin (mTOR) field started 2 decades before the identification of the mTOR kinase. Over the years, studies revealed that the mTOR signaling is a master regulator of homeostasis and integrates a variety of environmental signals to regulate cell growth, proliferation, and metabolism. Deregulation of mTOR signaling, particularly hyperactivation, frequently occurs in human tumors. Recent advances in molecular profiling have identified mutations or amplification of certain genes coding proteins involved in the mTOR pathway (e.g. PIK3CA, PTEN, STK11, and RICTOR) as the most common reasons contributing to mTOR hyperactivation. These genetic alterations of the mTOR pathway are frequently observed in lung neoplasms and may serve as a target for personalized therapy. mTOR inhibitor monotherapy has met limited clinical success so far; however, rational drug combinations are promising to improve efficacy and overcome acquired resistance. A better understanding of mTOR signaling may have the potential to help translation of mTOR pathway inhibitors into the clinical setting.
C1 [Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Khoor, Andras] Mayo Clinic, Department of Laboratory Medicine and Pathology, 4500 San Pablo Road, 32224 Jacksonville, FL, USA.
RP Khoor, A (reprint author), Mayo Clinic, Department of Laboratory Medicine and Pathology, 32224 Jacksonville, USA.
EM Khoor.Andras@mayo.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 35
EP 48
DI 10.1007/s12253-020-00796-1
PG 14
ER
PT J
AU Matyasi, B
Farkas, Zs
Kopper, L
Sebestyen, A
Boissan, M
Mehta, A
Takacs-Vellai, K
AF Matyasi, Barbara
Farkas, Zsolt
Kopper, Laszlo
Sebestyen, Anna
Boissan, Mathieu
Mehta, Anil
Takacs-Vellai, Krisztina
TI The Function of NM23-H1/NME1 and Its Homologs in Major Processes Linked to Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NDPK; Metastasis inhibitor; NM23; Phagocytosis; Apoptosis; Cell migration; Dynamin; Phosphohistidine; Cftr
ID NDPK; Metastasis inhibitor; NM23; Phagocytosis; Apoptosis; Cell migration; Dynamin; Phosphohistidine; Cftr
AB Metastasis suppressor genes (MSGs) inhibit different biological processes during metastatic progression without globally influencing development of the primary tumor. The first MSG, NM23 (non-metastatic clone 23, isoform H1) or now called NME1 (stands for nonmetastatic) was identified some decades ago. Since then, ten human NM23 paralogs forming two groups have been discovered. Group INM23 genes encode enzymes with evolutionarily highly conserved nucleoside diphosphate kinase (NDPK) activity. In this review we summarize how results from NDPKs in model organisms converged on human NM23 studies. Next, we examine the role of NM23-H1 and its homologs within the metastatic cascade, e.g. cell migration and invasion, proliferation and apoptosis. NM23-H1 homologs are well known inhibitors of cell migration. Drosophila studies revealed that AWD, the fly counterpart of NM23-H1 is a negative regulator of cell motility by modulating endocytosis of chemotactic receptors on the surface of migrating cells in cooperation with Shibire/ Dynamin; this mechanism has been recently confirmed by human studies. NM23-H1 inhibits proliferation of tumor cells by phosphorylating the MAPK scaffold, kinase suppressor of Ras (KSR), resulting in suppression of MAPK signaling. This mechanism was also observed with the C. elegans homolog, NDK-1, albeit with an inverse effect on MAPK activation. Both NM23-H1 and NDK-1 promote apoptotic cell death. In addition, NDK-1, NM23-H1 and their mouse counterpart NM23-M1 were shown to promote phagocytosis in an evolutionarily conserved manner. In summary, inhibition of cell migration and proliferation, alongside actions in apoptosis and phagocytosis are all mechanisms through which NM23-H1 acts against metastatic progression.
C1 [Matyasi, Barbara] Eotvos Lorand University, Institute of Biology, Department of Biological Anthropology, Pazmany Peter stny. 1/C, H-1117 Budapest, Hungary.
[Farkas, Zsolt] Eotvos Lorand University, Institute of Biology, Department of Biological Anthropology, Pazmany Peter stny. 1/C, H-1117 Budapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Boissan, Mathieu] Sorbonne Universite, INSERM, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.
[Mehta, Anil] Ninewells Hospital Medical School, Centre for CVS and Lung Biology, DD19SY Dundee, UK.
[Takacs-Vellai, Krisztina] Eotvos Lorand University, Institute of Biology, Department of Biological Anthropology, Pazmany Peter stny. 1/C, H-1117 Budapest, Hungary.
RP Takacs-Vellai, K (reprint author), Eotvos Lorand University, Institute of Biology, Department of Biological Anthropology, H-1117 Budapest, Hungary.
EM krisztina.takacs@ttk.elte.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 49
EP 61
DI 10.1007/s12253-020-00797-0
PG 13
ER
PT J
AU Deli, T
Orosz, M
Jakab, A
AF Deli, Tamas
Orosz, Monika
Jakab, Attila
TI Hormone Replacement Therapy in Cancer Survivors – Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Hormone replacement therapy; HRT; Menopausal hormone therapy; MHT; Estrogen replacement; Estrogen-progestin replacement; Oncologic patient; Cancer survivor; Gynecologic cancer; Non-gynecologic cancer; Breast cancer; Recurrence risk
ID Hormone replacement therapy; HRT; Menopausal hormone therapy; MHT; Estrogen replacement; Estrogen-progestin replacement; Oncologic patient; Cancer survivor; Gynecologic cancer; Non-gynecologic cancer; Breast cancer; Recurrence risk
AB Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symptoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed against the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advantageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is disadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).
C1 [Deli, Tamas] University Medical School of Debrecen, Department of Gynecology and ObstetricsDebrecen, Hungary.
[Orosz, Monika] University Medical School of Debrecen, Department of Gynecology and ObstetricsDebrecen, Hungary.
[Jakab, Attila] University Medical School of Debrecen, Department of Gynecology and ObstetricsDebrecen, Hungary.
RP Deli, T (reprint author), University Medical School of Debrecen, Department of Gynecology and Obstetrics, Debrecen, Hungary.
EM tamasdeli@yahoo.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 63
EP 78
DI 10.1007/s12253-018-00569-x
PG 16
ER
PT J
AU Evans, M
O’Sullivan, B
Hughes, F
Mullis, T
Smith, M
Trim, N
Taniere, P
AF Evans, Matthew
O’Sullivan, Brendan
Hughes, Frances
Mullis, Tina
Smith, Matthew
Trim, Nicola
Taniere, Philippe
TI The Clinicopathological and Molecular Associations of PD-L1 Expression in Non-small Cell Lung Cancer: Analysis of a Series of 10,005 Cases Tested with the 22C3 Assay
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; PD-L1; Immunotherapy; Pembrolizumab
ID Lung cancer; PD-L1; Immunotherapy; Pembrolizumab
AB PD-L1 expression testing is mandatory prior to pembrolizumab prescription in non-small cell lung cancer. Our service offers PDL1 testing using the PD-L1 IHC 22C3 pharmDx assay, in parallel with EGFR, ALK, ROS1 and (in some cases) KRAS testing. We correlate PD-L1 expression in 10,005 tumours with patient age and sex, with tumour histological subtypes, with the sampling modality and type of tissue, and with the presence of other molecular alterations. PD-L1 expression testing was performed using the aforementioned assay; tumour proportion scores (TPS) of 1 and 50% were taken as cut-offs for low and high positivity, respectively. EGFR testing was performed using the cobas® EGFR Mutation Test v2. ALK testing was performed using the VENTANA ALK (D5F3) CDx Assay. KRAS testing was performed using pyrosequencing. TPS <1% was seen in 44.4% of tumours, 1–49% in 25.0% and ≥ 50% in 30.6%.We identified no significant relationship with age. Female patients were slightly more likely to express PD-L1. Poorly-differentiated tumour histology and ALK translocation were significantly associated with PD-L1 expression. Rare EGFR mutations tended to be associated with PD-L1 expression. Pleural and nodal metastases were more likely to express PD-L1 than primary tumours, but biopsy and cytological specimens did not show different PD-L1 expression rates. Our data show that the means of acquiring a tumour sample (biopsy versus cytology) does not have a significant impact on PD-L1 expression. However, we found that certain metastatic sites were associated with significantly higher expression rates, which has substantial implications for selection of tissue for testing.
C1 [Evans, Matthew] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[O’Sullivan, Brendan] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[Hughes, Frances] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[Mullis, Tina] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[Smith, Matthew] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[Trim, Nicola] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
[Taniere, Philippe] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Mindelsohn Way, B15 2TH Birmingham, UK.
RP Evans, M (reprint author), Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, B15 2TH Birmingham, UK.
EM matthew.evans7@nhs.net
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 79
EP 89
DI 10.1007/s12253-018-0469-6
PG 11
ER
PT J
AU Du, J
Wang, S
Wang, R
Wang, SY
Han, Q
Xu, HT
Yang, P
Liu, Y
AF Du, Jiang
Wang, Si
Wang, Rui
Wang, Si-Yao
Han, Qiang
Xu, Hong-Tao
Yang, Peng
Liu, Yang
TI Identifying Secondary Mutations in Chinese Patients with Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs) by Next Generation Sequencing (NGS)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastrointestinal stromal tumors; Secondary mutation; Acquired resistance; Next generation sequencing
ID Gastrointestinal stromal tumors; Secondary mutation; Acquired resistance; Next generation sequencing
AB The aim of this study was to characterize secondary kinase mutations in Chinese patients with imatinib-resistant gastrointestinal stromal tumors (GISTs).Mutations in receptor tyrosine kinase (KIT; exons 9, 11, 13, 14, 17, and 18) and platelet-derived growth factor-alpha (PDGFRA; exons 12, 14, and 18) were analyzed by direct sequencing. After imatinib treatment, 425 cancer-related target genes were analyzed by next generation sequencing (NGS) in imatinib-resistant patients. Correlation of sequencing results with clinicopathologic features were analyzed. We identified 320 patients with secondary acquired resistance. We determined that 65.63% (210/320) of resistant patients had secondary KIT mutations in exon 13 (n = 134), exon 14 (n =10), or exon 17 (n = 66), and 4.38%(14/320) had additional PDGFRA mutations in exon 14 (n = 3) or exon 18 (n = 11). All secondary KIT mutations were missense mutations and were mostly located in kinase domains. Ninety-six imatinib-resistant GIST patients did not have secondary KIT or PDGFRA mutations. Common independent mutation events were found in retinoblastoma protein 1 (RB1) (18/96 cases), SWI/SNF-related matrix associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) (16/96 cases), and myc-associated factor X (MAX) (10/96 cases). RB1 or SMARCB1 mutations coexisted with activation of other oncogenes in 6 or 15 cases, respectively. Multiple mutations were also seen in cases with MAX mutations. These mutations are frequently associated with clinicopathological factors. Secondary mutations of KIT/PDGFRA were the most important contributors in GISTs developing resistance to imatinib treatment. Additional genetic events including RB1, SMARCB1, and MAX except secondary KIT/PDGFRA mutations are the most common for GISTs to evolve into resistant disease. Clinical assessment of the effect of these mutations may benefit existing risk assessment models and selection of adjuvant therapies in GIST patients.
C1 [Du, Jiang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Wang, Si] the College of Basic Medical Sciences of China Medical University, Department of Medical Microbiology and Human Parasitology, 110122 Shenyang, China.
[Wang, Rui] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Wang, Si-Yao] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Han, Qiang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Xu, Hong-Tao] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Yang, Peng] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
[Liu, Yang] China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
RP Liu, Y (reprint author), China Medical University, The First Affiliated Hospital and College of Basic Medical Sciences, Department of Pathology, 110122 Shenyang, China.
EM liuyanglovebee@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 91
EP 100
DI 10.1007/s12253-019-00770-6
PG 10
ER
PT J
AU Kocsis-Deak, B
Arvai, K
Balla, B
Tobias, B
Kohanka, A
Jaray, B
Horanyi, J
Podani, J
Takacs, I
Putz, Zs
Kosa, J
Lakatos, P
AF Kocsis-Deak, Barbara
Arvai, Kristof
Balla, Bernadett
Tobias, Balint
Kohanka, Andrea
Jaray, Balazs
Horanyi, Janos
Podani, Janos
Takacs, Istvan
Putz, Zsuzsanna
Kosa, Janos
Lakatos, Peter
TI Targeted Mutational Profiling and a Powerful Risk Score as Additional Tools for the Diagnosis of Papillary Thyroid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid cancer; New hotspot panel; Multivariate statistical method; Risk score; Next generation sequencing
ID Papillary thyroid cancer; New hotspot panel; Multivariate statistical method; Risk score; Next generation sequencing
AB Nowadays, the complementary diagnostics based on the suspicious thyroid lesion specific mutational state analysis is indispensable in the clinical practice. We aimed to test and validate our novel 568-mutational hotspot panel (23 cancer-related genes) on papillary thyroid cancers (PTCs) and their tumor-free pairs to find the most powerful mutation pattern related to PTC. The sequencing method was carried on with Ion Torrent PGM on 67 thyroid tissue samples. The most commonly detected mutation was the BRAF c.1799 T > A in all non-classical PTC cases. We utilized a multivariate statistical method (CVA) to determine a discrimination score based on mutational data array and to assess malignancy risk. Based on variants, the BRAF gene has by far the highest indicative power, followed by TSHR and APC. We highlighted novel aspects of the mutational profile and genetic markers of PTC. CVA has correctly assigned most of the samples based on the mutation frequencies and different variables of the selected genes, with high analytical probabilities. The final goal is to set up a new comprehensive rule-in and rule-out test to support the clinical decision making mainly in inconclusive fine-needle aspiration biopsy cases.
C1 [Kocsis-Deak, Barbara] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Arvai, Kristof] PentaCore LaboratoryBudapest, Hungary.
[Balla, Bernadett] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Tobias, Balint] PentaCore LaboratoryBudapest, Hungary.
[Kohanka, Andrea] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Jaray, Balazs] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Horanyi, Janos] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Podani, Janos] Eotvos Lorand University, Institute of BiologyBudapest, Hungary.
[Takacs, Istvan] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Putz, Zsuzsanna] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Kosa, Janos] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
[Lakatos, Peter] Semmelweis University, 1st Department of Internal Medicine, Koranyi Sandor Street 2/a, 1083 Budapest, Hungary.
RP Kocsis-Deak, B (reprint author), Semmelweis University, 1st Department of Internal Medicine, 1083 Budapest, Hungary.
EM kocsisd.barbi@gmail.com
CR Institute NC: Cancer stat facts: Thyroid cancer. Available from: https://seer.cancer.gov/statfacts/html/thyro.html. Accessed 12 Sept 2017
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 101
EP 108
DI 10.1007/s12253-019-00772-4
PG 8
ER
PT J
AU Tian, P
Cheng, X
Zhao, Z
Zhang, Y
Bao, C
Wang, Y
Cai, Sh
Ma, G
Huang, Y
AF Tian, Panwen
Cheng, Xiangyang
Zhao, Zhengyi
Zhang, Yuzi
Bao, Celimuge
Wang, Yanyan
Cai, Shangli
Ma, Guowei
Huang, Ying
TI Spectrum of Pathogenic Germline Mutations in Chinese Lung Cancer Patients through Next-Generation Sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Germline mutation; Next-generation sequencing; Lung cancer; DNA damage repair pathway
ID Germline mutation; Next-generation sequencing; Lung cancer; DNA damage repair pathway
AB Lung cancer is currently a leading cause of cancer-associated mortality worldwide. Despite the increasing evidences of variants that were associated with lung cancer risk, investigations of genetic factors and their roles in genetic susceptibility to lung cancer were limited. Here we systematically investigated the spectrum of pathogenic germline mutations in Chinese population with lung cancer. Genomic profiling of DNA was performed through next-generation sequencing (NGS) on tissue biopsy from 1764 Chinese lung cancer patients with a 381 cancer gene panel between January 01, 2017 and May 07, 2019. Patients with germline mutations were identified, and their clinical information were collected. Of 1764 patients with lung cancer, 67 (3.8%) patients were identified to carry pathogenic or likely pathogenic germline mutations in 25 cancer predisposition genes, with a frequency of 3.6% in lung adenocarcinoma (49/1349), 4.3% in squamous cell lung cancer (14/322), 5.6% in small cell lung cancer (4/72), and none in lung adenosquamous carcinoma (0/21), respectively. The highest pathogenic germline mutational prevalence were found in BRCA2 (0.79%), CHEK2 (0.40%), BRCA1 (0.34%), and TP53 (0.34%). Two splice mutations were reported for the first time in this study. Notably, a majority (85.5%) of the detected germline mutations fell in DNA damage repair pathways.
C1 [Tian, Panwen] Sichuan University, West China Hospital, Department of Respiratory MedicineChengdu, Sichuan, China.
[Cheng, Xiangyang] Guangzhou Medical College, First Affiliated HospitalGuangzhou, China.
[Zhao, Zhengyi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhang, Yuzi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Bao, Celimuge] 3D Medicines Inc., The Information System DepartmentShanghai, China.
[Wang, Yanyan] 3D Medicines Inc., The Information System DepartmentShanghai, China.
[Cai, Shangli] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Ma, Guowei] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Thoracic Surgery, 510060 Guangzhou, China.
[Huang, Ying] First Affiliated Hospital of Army Military Medical University, Department of Respiratory, 30 Gaotanyan Zhengjie, Shapingba District, 400038 Chongqing, China.
RP Huang, Y (reprint author), First Affiliated Hospital of Army Military Medical University, Department of Respiratory, 400038 Chongqing, China.
EM hga_83@sina.com
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. , DOI 10.3322/caac. 21492
Tibaldi C, Giovannetti E, Vasile E, Boldrini L, Gallegos-Ruiz MI, Bernardini I, Incensati R, Danesi R, Cappuzzo F, Peters GJ, Fontanini G, 2011, Inherited germline T790Mmutation and somatic epidermal growth factor receptormutations in non-small cell lung cancer patients. J Thorac Oncol 6(2):395–396. , DOI 10. 1097/JTO.0b013e3182059a6f
Lu S, Yu Y, Li Z, Yu R, Wu X, Bao H, Ding Y, Shao YW, Jian H, 2019, EGFR and ERBB2 Germline mutations in Chinese lung Cancer patients and their roles in genetic susceptibility to Cancer. J Thorac Oncol 14(4):732–736. , DOI 10.1016/j.jtho.2018. 12.006
Oxnard GR, Nguyen KS, Costa DB, 2014, Germline mutations in driver oncogenes and inherited lung cancer risk independent of smoking history. J Natl Cancer Inst 106(1):djt361. , DOI 10.1093/jnci/djt361
Parry EM, Gable DL, Stanley SE, Khalil SE, Antonescu V, Florea L, ArmaniosM(2017, Germline mutations in DNA repair genes in lung adenocarcinoma. J Thorac Oncol 12(11):1673–1678. https:// doi.org/10.1016/j.jtho.2017.08.011
Couto PP, Bastos-Rodrigues L, Schayek H,Melo FM, Lisboa RGC, MirandaDM,VilhenaA, Bale AE, Friedman E, DeMarco L, 2017, Spectrum of germline mutations in smokers and non-smokers in Brazilian non-small-cell lung cancer, NSCLC, patients. Carcinogenesis 38(11):1112–1118. , DOI 10.1093/carcin/ bgx089
Su D, Zhang D, Chen K, Lu J, Wu J, Cao X, Ying L, Jin Q, Ye Y, Xie Z, Xiong L, MaoW, Li F, 2017, High performance of targeted next generation sequencing on variance detection in clinical tumor specimens in comparison with current conventional methods. J Exp Clin Cancer Res 36(1):121. , DOI 10.1186/s13046-017- 0591-4
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ALQA, 2015, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405– 424. , DOI 10.1038/gim.2015.30
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Gou LY, Wu YL, 2014, Prevalence of driver mutations in nonsmall- cell lung cancers in the People's Republic of China. Lung Cancer, Auckland, NZ, 5:1–9. , DOI 10.2147/LCTT. S40817
Oxnard GR, Miller VA, Robson ME, Azzoli CG, Pao W, Ladanyi M, Arcila ME, 2012, Screening for germline EGFR T790M mutations through lung cancer genotyping. J Thorac Oncol 7(6):1049– 1052. , DOI 10.1097/JTO.0b013e318250ed9d
Daly MB, Pilarski R, Berry M, Buys SS, Farmer M, Friedman S, Garber JE, Kauff ND, Khan S, Klein C, Kohlmann W, Kurian A, Litton JK, Madlensky L, Merajver SD, Offit K, Pal T, Reiser G, Shannon KM, Swisher E, Vinayak S, Voian NC, Weitzel JN, Wick MJ, Wiesner GL, Dwyer M, Darlow S, 2017, NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Cancer Netw 15(1):9–20
Gourley C, Balmana J, Ledermann JA, Serra V, Dent R, Loibl S, Pujade-Lauraine E, Boulton SJ, 2019, Moving from poly, ADPribose, polymerase inhibition to targeting DNA repair and DNA damage response in Cancer therapy. J Clin Oncol: JCO1802050. , DOI 10.1200/JCO.18.02050
Sen T, Rodriguez BL, Chen L, Corte CMD,Morikawa N, Fujimoto J, Cristea S, Nguyen T, Diao L, Li L, Fan Y, Yang Y, Wang J, Glisson BS, Wistuba II, Sage J, Heymach JV, Gibbons DL, Byers LA, 2019, Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung Cancer. Cancer Discov 9(5):646–661. , DOI 10.1158/ 2159-8290.CD-18-1020
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 109
EP 114
DI 10.1007/s12253-019-00771-5
PG 6
ER
PT J
AU Yu, L
Yang, JSh
AF Yu, Lu
Yang, Jing Shou
TI Primary Osteosarcoma of the Liver: Case Report and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Mesenchymal tumor; Hepatic; Osteoid; Extraskeletal osteosarcoma
ID Mesenchymal tumor; Hepatic; Osteoid; Extraskeletal osteosarcoma
AB Extraskeletal osteosarcoma is a rare, highly malignant, osteoid formation mesenchymal neoplasm in the absence of bone involvement, associated with exceptionally poor prognosis. It frequently arises in the soft tissues of the extremities or in the retroperitoneum, but rarely in visceral organ. We describe a primary osteosarcoma of the liver in a 70-year-old man who presented with an episode of fever, accompanied by abdominal discomfort, after an accident abdominal strike. Ultrasonography and computed tomography revealed a large heterogeneous mass with areas of dense calcification involving most of the right lobe of liver. Radiography did not show evidence of primary tumor or primary bone lesion at any other site. Histologically, the tumor showed an essentially similar appearance as osteosarcoma originating in the skeleton, comprised of polygonal or spindle shaped cells, along with abundant eosinophilic lace-like osteoids, or irregularly arranged bone trabeculae. Immunohistochemistry showed that the tumor cells were positive for vimentin, CD10, and focally for SMA and CD56, but negative for other lineage-specific markers. Thus, the findings favored a primary hepatic osteosarcoma. This patient received palliative chemotherapy to ease the signs of his sickness due to the large size of the tumor and he died 4 months later.
C1 [Yu, Lu] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 169 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
[Yang, Jing Shou] Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, No. 169 Chang Le Xi Road, 710032 Xi’an, Shaanxi, China.
RP Yang, JSh (reprint author), Fourth Military Medical University, Xijing Hospital, State Key Laboratory of Cancer Biology and Department of Pathology, 710032 Xi’an, China.
EM yangsj@fmmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 115
EP 120
DI 10.1007/s12253-018-0483-8
PG 6
ER
PT J
AU Sun, X
Guo, Sh
AF Sun, Xiaojun
Guo, Shilei
TI The Prognostic and Predictive Value of Dihydropyrimidine Dehydrogenase-Related Indicators in Clinical Outcomes of Chemotherapy in Colorectal Cancer Patients: a Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Dihydropyrimidine dehydrogenase; Thymidylate phosphorylase; Colorectal cancer; Meta-analysis
ID Dihydropyrimidine dehydrogenase; Thymidylate phosphorylase; Colorectal cancer; Meta-analysis
AB Colorectal cancer (CRC) is the third most common cancer worldwide. Predictive biomarkers are needed to predict patients’ outcomes and to select a chemotherapy regimen. We assessed whether dihydropyrimidine dehydrogenase (DPD)-related indicators can predict CRC patients’ outcomes. We searched the studies in PubMed, EmBase, and the Cochrane Library up to March 4, 2018.We mainly analyzed different CRC patients’ outcomes according to specific DPD-related indicators. Twenty-five articles were included in the meta-analysis. The results showed that for disease-free survival (DFS), low DPD expression was significantly superior to high expression (I2 = 72%; HR: 1.59; 95%CI: 1.21–2.09; p = 0.001). However, this result had a potential publication bias (Begg’s test: p = 0.007; Egger’s test: p = 0.004). Among patients treated with chemotherapy, a high thymidylate phosphorylase (TP)/DPD ratio was advantageous for DFS (I2 = 63.7%; HR: 0.65; 95%CI: 0.46–0.92; p = 0.015), and this result did not have a publication bias. For overall survival (OS), low DPD expression was superior to high expression (I2 = 74.4%;HR: 2.11; 95%CI: 1.48–3.00; p < 0.001), although this result had a publication bias (Egger’s test: p = 0.003; Begg’s test: p = 0.010). There was no difference in OS according to the TP/DPD ratio (I2 = 0%; HR: 0.92; 95%CI: 0.75–1.13; p = 0.420). DFS and OS were better in CRC patients with low DPD expression than in those with high DPD expression. However, because of publication bias, more DPD indicator-related studies, especially with negative results, are still needed. Patients with a high TP/DPD ratio have better DFS but not OS.
C1 [Sun, Xiaojun] Nanjing Qi-xia Xi-gang community health service centers, Inpatients department, 210033 Nanjing, Jiangsu, China.
[Guo, Shilei] Nanjing Regenerative Medicine Engineering and Technology Research Center, R&D department, No.108, Ganjiabian East, Qixia District, 210046 Nanjing, Jiangsu, China.
RP Guo, Sh (reprint author), Nanjing Regenerative Medicine Engineering and Technology Research Center, R&D department, 210046 Nanjing, China.
EM guoshilei1986@aliyun.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 121
EP 131
DI 10.1007/s12253-018-00563-3
PG 11
ER
PT J
AU Roberto, MG
Delsin, EL
Vieira, MG
Silva, OM
Hakime, GR
Gava, FN
Engel, EE
Scrideli, AC
Tone, GL
Brassesco, SM
AF Roberto, Molinari Gabriela
Delsin, Elis Lara
Vieira, Maciel Gabriela
Silva, Oliveira Marcela
Hakime, Guedes Rodrigo
Gava, Fabricio Nelson
Engel, Eduard Edgard
Scrideli, Alberto Carlos
Tone, Gonzaga Luiz
Brassesco, Sol Maria
TI ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rock; microRNA; Ewing sarcoma; Invasion; Motility
ID Rock; microRNA; Ewing sarcoma; Invasion; Motility
AB Over the last decade, the rho-associated kinases and several metastasis-associated microRNAs have emerged as important contributors of tumor invasion. However, despite prominence, our understanding of their involvement in the metastatic potential of Ewing Sarcoma (EWS) is incomplete. The expression profiles of ROCK1 or ROCK2 and miR- 124-3p, miR-138-5p, miR-139-5p, miR-335-5p and miR-584-5p (all of which were previously predicted or validated to regulate these kinases) were evaluated through qRT-PCR and associated with clinical parameters. In vitro assays to evaluate colony formation and invasion/migration capacities were performed on SK-ES-1 cells transfected with premiR mimics. ROCK1 expression was significantly reduced in EWS tissues, though there was no association with pathological parameters. miR-124-3p, miR-139-5p and miR-335-3p were also found significantly downregulated and positively correlated with ROCK1. Stratification indicated an association between lower levels of miR-139-5p and miR- 584-5p with disease progression (p < 0.05), while reduced expression of the former and miR-124-3p were associated with reduced survival. In vitro miR-139-5p overexpression yielded inconsistent results: while mir-139-5p restoration significantly reduced invasion, the clonogenic capacity of cells was increased. Our study demonstrated that downregulation of miR-124-3p, miR-139-5p and miR-584-5p are associated with disease progression in EWS and may serve as a risk assessment biomarkers though, as seen for mir-139-5p, their specific role remain to be elucidated for considering tailoring treatment options.
C1 [Roberto, Molinari Gabriela] University of Sao Paulo, Ribeirao Preto School of Medicine, Regional Blood CenterSao Paulo, Brazil.
[Delsin, Elis Lara] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of GeneticsSao Paulo, Brazil.
[Vieira, Maciel Gabriela] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of GeneticsSao Paulo, Brazil.
[Silva, Oliveira Marcela] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell BiologySao Paulo, Brazil.
[Hakime, Guedes Rodrigo] University of Sao Paulo, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, Department of BiologySao Paulo, Brazil.
[Gava, Fabricio Nelson] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
[Engel, Eduard Edgard] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
[Scrideli, Alberto Carlos] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Tone, Gonzaga Luiz] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Brassesco, Sol Maria] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
RP Brassesco, SM (reprint author), University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Sao Paulo, Brazil.
EM solbrassesco@usp.br
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Gao CF, Xie Q, Su YL, Koeman J, Khoo SK, Gustafson M et al, 2005, Proliferation and invasion: plasticity in tumor cells. Proc Natl Acad Sci USA 102:10528–10533
Hecht I, Natan S, Zaritsky A, Levine H, Tsarfaty I, Ben-Jacob E, 2015, The motility-proliferation-metabolism interplay during metastatic invasion. Sci Rep 5:13538
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 133
EP 139
DI 10.1007/s12253-017-0374-4
PG 7
ER
PT J
AU Ghali, MR
Al-Mutawa, AM
Ebrahim, HB
Jrah, HH
Zaied, S
Bhiri, H
Hmila, F
Mahjoub, T
Almawi, YW
AF Ghali, M Rabeb
Al-Mutawa, A Maryam
Ebrahim, H Bashayer
Jrah, H Hanen
Zaied, Sonia
Bhiri, Hanen
Hmila, Fahmi
Mahjoub, Touhami
Almawi, Y Wassim
TI Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Haplotypes; Mutation; Progesterone; Progesterone receptor
ID Breast cancer; Haplotypes; Mutation; Progesterone; Progesterone receptor
AB Insofar as altered estrogen receptor-progesterone receptor (PR) expression contribute to breast cancer pathogenesis, previous studies examined the association of genetic variation in PR gene (PGR) with breast cancer, but with mixed outcome. We evaluated the association between PGR variants, and breast cancer and associated features. A retrospective case-control study involving 183 female breast cancer patients, and 222 control women. PGR genotyping was done by real-time PCR. Minor allele frequencies of rs1042838, rs590688, and rs10895068 PGR gene polymorphisms were significantly higher in breast cancer patients compared to controls. Patients carrying rs1042838 G/T, rs590688 C/C, and rs10895068 G/A genotypes had higher risk of breast cancer, while carriage of rs3740753 G/G genotype was associated with marginal reduction in breast cancer risk. In addition, carriage of rs1042839, rs3740753, and rs10895068 minor allele was associated with Her2 status, while rs3740753 and rs10895068 were associated with effective hormone replacement therapy. Furthermore, carriage of rs10895068 minor allele in breast cancer women were also associated with age at first pregnancy, hormone receptor (RH) status, and previous use of oral contraceptives. PGR haploview analysis documented moderate-strong linkage disequilibrium (non-random association of alleles at different loci) between 7 of the 8 tested PGR SNPs, thus allowing construction of 7-locus PGR haplotypes. Two haplotypes, ATGCCGA and GTGCCGA, both containing rs590688, were positively associated with breast cancer, thus assigning a breast cancer-susceptible nature to these haplotypes. PGR rs1042838, rs590688, and rs10895068, and ATGCCGA and GTGCCGA haplotypes are related with increased breast cancer susceptibility in Tunisian women.
C1 [Ghali, M Rabeb] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Al-Mutawa, A Maryam] El Manar University, Faculty of Sciences of Tunis, Manar II, 2092 Tunis, Tunisia.
[Ebrahim, H Bashayer] El Manar University, Faculty of Sciences of Tunis, Manar II, 2092 Tunis, Tunisia.
[Jrah, H Hanen] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Zaied, Sonia] CHU Fattouma Bourguiba, Department of Clinical OncologyMonastir, Tunisia.
[Bhiri, Hanen] CHU Fattouma Bourguiba, Department of Clinical OncologyMonastir, Tunisia.
[Hmila, Fahmi] CHU Farhat Hached, Department of SurgerySousse, Tunisia.
[Mahjoub, Touhami] University of Monastir, Faculty of Pharmacy of Monastir, Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)Monastir, Tunisia.
[Almawi, Y Wassim] El Manar University, Faculty of Sciences of Tunis, Manar II, 2092 Tunis, Tunisia.
RP Almawi, YW (reprint author), El Manar University, Faculty of Sciences of Tunis, 2092 Tunis, Tunisia.
EM wassim.almawi@outlook.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 141
EP 147
DI 10.1007/s12253-017-0379-z
PG 7
ER
PT J
AU Dobi,
Fodor, E
Maraz, A
Egyud, Zs
Cserhati, A
Tiszlavicz, L
Reisz, Z
Barzo, P
Varga, Z
Hideghety, K
AF Dobi, Agnes
Fodor, Emese
Maraz, Aniko
Egyud, Zsofia
Cserhati, Adrienne
Tiszlavicz, Laszlo
Reisz, Zita
Barzo, Pal
Varga, Zoltan
Hideghety, Katalin
TI Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of Brain Metastases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE WBRT; Simultaneous integrated boost; Brain metastasis .3DCRT; IMRT
ID WBRT; Simultaneous integrated boost; Brain metastasis .3DCRT; IMRT
AB Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung cancer and melanoma and both for oligo- and multiplex lesions. The OS was prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose, 4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p < 0.0001) in the class RPA 3 respectively. The significant difference in OS was also achieved with SIB. The shortened overall treatment time of SIB with lower WBRT fraction dose exhibited survival benefit over WBRT alone, and could be applied for patients developing BM even with unfavourable prognostic factors. These results warrant for further study of this approach with dose escalation using the lately available solutions for hippocampus sparing and fractionated stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction dose and boost proved to be advantageous prolonging the OS with shortened treatment time and reduced probability for cognitive decline development even for patients with poor performance status and progressing extracranial disease.
C1 [Dobi, Agnes] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Fodor, Emese] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Maraz, Aniko] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Egyud, Zsofia] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Cserhati, Adrienne] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, Allomas utca 1, H-6725 Szeged, Hungary.
[Reisz, Zita] University of Szeged, Department of Pathology, Allomas utca 1, H-6725 Szeged, Hungary.
[Barzo, Pal] University of Szeged, Department of Neurosurgery, Semmelweis utca 8, H-6725 Szeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Hideghety, Katalin] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
RP Dobi, (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
EM dobiagnes@gmail.com
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Bruzzaniti V, Abate A, Pedrini M, Benassi M, Strigari L, 2011, IsoBED: a tool for automatic calculation of biologically equivalent fractionation schedules in radiotherapy using IMRTwith a simultaneous integrated boost, SIB, technique. J Exp Clin Cancer Res 30: 52
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Kocher M, Soffietti R, Abacioglu U et al, 2011, Adjuvant wholebrain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29:134–141
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 149
EP 157
DI 10.1007/s12253-018-0383-y
PG 9
ER
PT J
AU Wang, JX
Wu, HL
Zhu, M
Zhou, R
AF Wang, Jian-Xiang
Wu, Hai-Long
Zhu, Meng
Zhou, Rui
TI Role of Anti-Epidermal Growth Factor Receptor Therapy Compared with Anti-Vascular Endothelial Growth Factor Therapy for Metastatic Colorectal Cancer: an Update Meta-Analysis of Randomized Clinical Trials
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Anti-EGFR; Anti-VEGF; Chemotherapy; Meta-analysis
ID Colorectal cancer; Anti-EGFR; Anti-VEGF; Chemotherapy; Meta-analysis
AB Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have showed clinical benefit in combination with chemotherapeutic cytotoxic drugs in the first-line therapy of metastatic colorectal cancer (mCRC). Data from randomized studies comparing these monoclonal antibodies as initial therapy is conflicting, and their comparative efficacy remains unknown. This study aimed to evaluate the impact of the combination of anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy on mCRC patient outcomes by combining the data from randomized clinical trials. Three trials meeting the eligibility criteria, and four randomized studies were included in the meta-analysis. For MCRC patients with KRAS wild type (KRAS-WT), the ORR was superior in patients treated with anti-EGFR compared with those who treated with anti-VEGF therapy. This effect was even better for all RAS-WT patients. Progression-free survival (PFS) rates were not significantly different for KRAS-WT mCRC and all RAS-WT mCRC between the two groups. The overall survival (OS) was higher for RAS wild-type (RAS-WT) mCRC patients who received anti-EGFR, but the KRAS-WT patients compared to the anti-VEGF therapy. The results of our research indicate that superior ORR and OS between the addition of anti-EGFR therapy VS anti-VEGF therapy in all RAS-WT patients with MCRC. There was no significant difference in OS and PFS between the two groups for KRAS-WT mCRC. These results suggest that anti- EGFR monoclonal antibodies can achieve an equivalent efficacy when compared with anti-VEGF therapy of all RAS-WT mCRC patients.
C1 [Wang, Jian-Xiang] Huazhong University of Science and Technology, Puai Hospital, Department of General Surgery, No. 473 Hanzheng Street, Qiaokou District, 430033 Wuhan, China.
[Wu, Hai-Long] Huazhong University of Science and Technology, Puai Hospital, Department of General Surgery, No. 473 Hanzheng Street, Qiaokou District, 430033 Wuhan, China.
[Zhu, Meng] Huazhong University of Science and Technology, Puai Hospital, Department of General Surgery, No. 473 Hanzheng Street, Qiaokou District, 430033 Wuhan, China.
[Zhou, Rui] Huazhong University of Science and Technology, Puai Hospital, Department of General Surgery, No. 473 Hanzheng Street, Qiaokou District, 430033 Wuhan, China.
RP Zhou, R (reprint author), Huazhong University of Science and Technology, Puai Hospital, Department of General Surgery, 430033 Wuhan, China.
EM zhourui0815@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 159
EP 166
DI 10.1007/s12253-017-0365-5
PG 8
ER
PT J
AU Fernandez-Vega, I
Santos-Juanes, J
Camacho-Urkaray, E
Lorente-Gea, L
Garcia, B
Gutierrez-Corres, BF
Quiros, ML
Guerra-Merino, I
Aguirre, JJ
AF Fernandez-Vega, Ivan
Santos-Juanes, Jorge
Camacho-Urkaray, Emma
Lorente-Gea, Laura
Garcia, Beatriz
Gutierrez-Corres, Borja Francisco
Quiros, M Luis
Guerra-Merino, Isabel
Aguirre, Javier Jose
TI Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Miki; Immunohistochemistry; Liver; Immunoglobulin superfamily
ID Hepatocellular carcinoma; Miki; Immunohistochemistry; Liver; Immunoglobulin superfamily
AB Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.
C1 [Fernandez-Vega, Ivan] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
[Santos-Juanes, Jorge] Hospital Universitario Central de Asturias, Department of PathologyOviedo, Spain.
[Camacho-Urkaray, Emma] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
[Lorente-Gea, Laura] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
[Garcia, Beatriz] Instituto Universitario Fernandez-VegaOviedo, Spain.
[Gutierrez-Corres, Borja Francisco] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
[Quiros, M Luis] Instituto Universitario Fernandez-VegaOviedo, Spain.
[Guerra-Merino, Isabel] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
[Aguirre, Javier Jose] Hospital Universitario de Araba-Txagorritxu, Department of PathologyVitoria-Gasteiz, Spain.
RP Fernandez-Vega, I (reprint author), Hospital Universitario de Araba-Txagorritxu, Department of Pathology, Vitoria-Gasteiz, Spain.
EM ivan_fernandez_vega@hotmail.com
CR Stoot JH, Coelen RJ, De Jong MC, Dejong CH, 2010, Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: a systematic review including more than 1600 adenoma cases. HPB 12:509–522
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 167
EP 173
DI 10.1007/s12253-018-0387-7
PG 7
ER
PT J
AU da Silva, NLJ
Ranzi, DA
Carvalho, TC
Scheide, VT
Strey, ThMY
Graziottin, MT
Bica, GC
AF da Silva, Niederauer Leote Jessica
Ranzi, Durayski Alana
Carvalho, Trainotti Caroline
Scheide, Vicente Tales
Strey, Thome Machado Yuri
Graziottin, Meyer Tulio
Bica, Giuliano Claudia
TI Cell Cycle Markers in the Evaluation of Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Cell cycle markers; Prognosis; Immunohistochemistry
ID Bladder cancer; Cell cycle markers; Prognosis; Immunohistochemistry
AB Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chi square, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free survival (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.
C1 [da Silva, Niederauer Leote Jessica] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Ranzi, Durayski Alana] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Carvalho, Trainotti Caroline] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Scheide, Vicente Tales] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Strey, Thome Machado Yuri] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Graziottin, Meyer Tulio] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
[Bica, Giuliano Claudia] Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, 245 Sarmento Leite, RS 90050-170 Porto Alegre, Brazil.
RP Bica, GC (reprint author), Health Sciences Federal University of Porto Alegre (UFCSPA), Research Laboratory of Pathology, RS 90050-170 Porto Alegre, Brazil.
EM claudia@ufcspa.edu.br
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 175
EP 181
DI 10.1007/s12253-018-0389-5
PG 7
ER
PT J
AU Gkouveris, I
Nikitakis, N
Sklavounou, A
AF Gkouveris, Ioannis
Nikitakis, Nikolaos
Sklavounou, Alexandra
TI p38 Expression and Modulation of STAT3 Signaling in Oral Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p38; STAT3; Oral cancer; Tumor grade
ID p38; STAT3; Oral cancer; Tumor grade
AB p38 protein belongs to Mitogen-activated protein kinases family that link extracellular stimuli with intracellular responses participating in numerous of fundamental cell processes. Persistent activation of STAT3 has been associated with cell proliferation, differentiation and apoptosis in oral squamous cell carcinoma (OSCC). This study examines the effects of p38 modulation on STAT3 signaling and cellular activities in OSCC cells and investigates possible correlation of p38 expression with tumor degree of differentiation. Phosphop38 immunostaining was performed in 60 OSCC including well, moderately and poorly differentiated tumors. Semiquantitative analysis was used, by calculating intensity, percentage and combined scores. Protein expression levels of STAT3 (total, tyrosine and serine phosphorylated), p38 and cyclin D1 were assessed in two OSCC cell lines. p38 inhibition was achieved by pharmacological agent (SB2023580). Cell proliferation and viability rates were also evaluated. Phospho-p38 immunoexpression was intense in almost all tumor specimens, nevertheless, did not correlate with tumor differentiation. Inhibition of p38 with SB203580 did not appear to affect tyrosine or serine phosphorylated STAT3 as well as cyclin D1 levels in both cell lines. Moreover, p38 inhibition resulted in mild dose dependent decreases in cell growth and viability in both cell lines. p38 is highly expressed in OSCC but does not seem to mediate the oncogenic STAT3 pathway. However, changes found in proliferation and viability may suggest that p38 functions as potent regulator of HNSCC. Understanding the complexity of p38 signaling and crosstalk between other major molecules, may guide the development of novel pharmacologic therapies for cancer treatment and prevention.
C1 [Gkouveris, Ioannis] National and Kapodistrian University of Athens, Dental School, Department of Oral Pathology and Medicine, 2 Thivon Str. Goudi, 11527 Athens, Greece.
[Nikitakis, Nikolaos] National and Kapodistrian University of Athens, Dental School, Department of Oral Pathology and Medicine, 2 Thivon Str. Goudi, 11527 Athens, Greece.
[Sklavounou, Alexandra] National and Kapodistrian University of Athens, Dental School, Department of Oral Pathology and Medicine, 2 Thivon Str. Goudi, 11527 Athens, Greece.
RP Gkouveris, I (reprint author), National and Kapodistrian University of Athens, Dental School, Department of Oral Pathology and Medicine, 11527 Athens, Greece.
EM igkouver@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 183
EP 192
DI 10.1007/s12253-018-0405-9
PG 10
ER
PT J
AU Damodaran, M
Paul, FDS
Venkatesan, V
AF Damodaran, Mohan
Paul, F D Solomon
Venkatesan, Vettriselvi
TI Genetic Polymorphisms in miR-146a, miR-196a2 and miR-125a Genes and its Association in Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNA; Prostate cancer; Genotyping; Haplotypes
ID microRNA; Prostate cancer; Genotyping; Haplotypes
AB The increase in incidence of prostate cancer in the Indian Population stresses the need to identify genetic markers for susceptibility and prognosis. Recent studies show that microRNAs play an important role in tumorigenesis by altering proliferation, differentiation and cell death. Gene polymorphisms not only in promoter region but also within miRNA gene have been shown to affect expression. The present study was aimed to analyze the role of miR-146a, miR-196a2 and miR-125a gene polymorphisms in prostate cancer. Genotyping of three SNPs rs73318382, rs57095329, rs2910164 in miRNA146a, rs11614913 in miR-196a2 and rs41275794, rs12976445, rs10404453 and rs1297533 in miR-125a was performed in 100 cases and 100 controls. Statistical analysis revealed the heterozygous AG genotype of the rs57095329 was significantly decreased in the cases when compared to the controls (OR-0.45, CI -0.24 to 0.85, p value-0.02) indicating an inverse association of this genotype with prostate cancer. Further the heterozygous CT of miR-196a2 (rs11614913) (OR-1.88, CI-1.06 to 3.35, p-0.02) and homozygous CC of miR-125a (rs12976445) (OR-2.55, CI -1.15 to 4.65, p-0.03) showed increased risk for prostate cancer. Combined analysis of all the genotypes revealed that the haplotype combination AGGCGTGG (OR = 0.09 at CI 95% (0.01–0.65) showed an inverse association with prostate cancer. Stratified analysis based on the age and tumor grade revealed no significant association.
C1 [Damodaran, Mohan] Sri Ramachandra University, Department of Human Genetics, 600116 Chennai, India.
[Paul, F D Solomon] Sri Ramachandra University, Department of Human Genetics, 600116 Chennai, India.
[Venkatesan, Vettriselvi] Sri Ramachandra University, Department of Human Genetics, 600116 Chennai, India.
RP Venkatesan, V (reprint author), Sri Ramachandra University, Department of Human Genetics, 600116 Chennai, India.
EM vettriselviv@yahoo.com
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Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A,Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM, 2005, MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 193
EP 200
DI 10.1007/s12253-018-0412-x
PG 8
ER
PT J
AU Cui, K
Zou, H
Shi, M
Ou, Y
Han, L
Zhang, B
Hu, D
Li, Sh
AF Cui, Kai
Zou, Hongsheng
Shi, Mingliang
Ou, Yang
Han, Lu
Zhang, Bo
Hu, Dawei
Li, Sheng
TI Gene Expression Profiles in Chemokine (C-C Motif) Ligand 21-Overexpressing Pancreatic Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chemokine (C-C motif) ligand 21; Pancreatic cancer cell; Lentiviral transduction; DNA microarray; Matrix metallopeptidase-9
ID Chemokine (C-C motif) ligand 21; Pancreatic cancer cell; Lentiviral transduction; DNA microarray; Matrix metallopeptidase-9
AB Chemokine (C-C Motif) ligand 21 (CCL21) plays an important role in tumor immunity. However, the molecular mechanisms by which CCL21 regulates tumor immunity remain largely unknown. In this study, we successfully generated a lentiviral vector expressing human CCL21 (Lenti-hCCL21), which was confirmed by biological assays. The Lenti-hCCL21 was transduced into PANC-1 cells, a chemokine (C-C motif) receptor 7 (CCR7)-positive human pancreatic cancer cell line. We used the scratch wound and transwell assays to measure cell migration of the CCL21-overexpressing PANC-1 cells. A DNA microarray assay was performed to determine gene expression profiles. The results showed that CCL21 lentiviral transduction significantly up- or down-regulated a panel of tumor-associated genes, although CCL21 appeared to have no effect on PANC-1 cell migration. Importantly, CCL21 promoted matrix metallopeptidase-9 (MMP-9) expression in PANC-1 cells. CCL21 regulates pancreatic cancer immunity possibly through governing the expression of a panel of tumor-associated genes, including MMP-9.
C1 [Cui, Kai] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
[Zou, Hongsheng] People’s Hospital of Rongcheng, 264300 Rongcheng, Shandong, China.
[Shi, Mingliang] People’s Hospital of Laiwu City, 271199 Laiwu, Shandong, China.
[Ou, Yang] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
[Han, Lu] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
[Zhang, Bo] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
[Hu, Dawei] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
[Li, Sheng] Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, Shandong, China.
RP Hu, D (reprint author), Shandong Cancer Hospital Affiliated to Shandong University, 250117 Jinan, China.
EM ckjason@sohu.com
CR Yadav D, Lowenfels AB, 2013, The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 144(6):1252–1261. https:// doi.org/10.1053/j.gastro.2013.01.068
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Xu Y, Li Z, Jiang P,Wu G, Chen K, Zhang X, Li X, 2015, The coexpression of MMP-9 and Tenascin-C is significantly associated with the progression and prognosis of pancreatic cancer. Diagn Pathol 10:211. , DOI 10.1186/s13000-015-0445-3
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 201
EP 208
DI 10.1007/s12253-018-0390-z
PG 8
ER
PT J
AU Wang, Z
Zhang, L
Wan, Z
He, Y
Huang, H
Xiang, H
Wu, X
Zhang, K
Liu, Y
Goodin, S
Du, Z
Zheng, X
AF Wang, Zhenshi
Zhang, Lanyue
Wan, Zheng
He, Yan
Huang, Huarong
Xiang, Hongping
Wu, Xiaofeng
Zhang, Kun
Liu, Yang
Goodin, Susan
Du, Zhiyun
Zheng, Xi
TI Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Atorvastatin; Apoptosis; Caffeine; Combination treatment; Prostate cancer
ID Atorvastatin; Apoptosis; Caffeine; Combination treatment; Prostate cancer
AB Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.
C1 [Wang, Zhenshi] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Zhang, Lanyue] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Wan, Zheng] Rutgers, The State University of New Jersey, Ernest Mario School of Pharmacy, Department of Chemical Biology, 08854 Piscataway, NJ, USA.
[He, Yan] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Huang, Huarong] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Xiang, Hongping] Guangdong University of Technology, School of Materials and Energy, Guangdong Provincial Key Laboratory of Functional Soft Condensed Matter, 510006 Guangzhou, China.
[Wu, Xiaofeng] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Zhang, Kun] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Liu, Yang] Xiamen University, Medical college, Department of Nursing, 361000 Xiamen, China.
[Goodin, Susan] Rutgers Cancer Institute of New Jersey, 08903 New Brunswick, NJ, USA.
[Du, Zhiyun] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
[Zheng, Xi] Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
RP Du, Z (reprint author), Guangdong University of Technology, Allan H. Conney Laboratory for Anticancer Research, 510006 Guangzhou, China.
EM zhiyundugdut@foxmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 209
EP 216
DI 10.1007/s12253-018-0415-7
PG 8
ER
PT J
AU Zidi, S
Sahli, M
Mezlini, A
Yacoubli-Loueslati, B
AF Zidi, Sabrina
Sahli, Mariem
Mezlini, Amel
Yacoubli-Loueslati, Besma
TI Association of Combined Tobacco Smoking, Hormonal Contraceptive use and Status Matrimonial with Cervical Cancer Evolution in Tunisian Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; FIGO staging; Status matrimonial; Smoking; Hormonal contraceptive
ID Cervical cancer; FIGO staging; Status matrimonial; Smoking; Hormonal contraceptive
AB Status matrimonial, cigarette smoking and hormonal contraceptive (HC) use have been associated with cervical cancer (CC) establishment by influencing the CC carcinogenesis process. In the present study, we aim to confirm this correlation between these factors and the risk of CC occurrence among Tunisian population. To evaluate the role of matrimonial status, smoking and HC as cofactors of CC installation, we performed a random selection of 600 women from Salah Azeiz institute in Tunisia and a questionnaire was conducted by doctors for each patient. Logistic regression after adjustment for potential confounding factors, relative excess risk due to interaction (RERI) and synergy index (S) were used to evaluate the additive interaction. Subgroup analysis was conducted to examine whether the relative risks changed with CC stages. There were an excess risk among smoker patients and patient with HC use (p < 0.001) for CC installation. Women who are smokers have a 14 times greater risk of suffering from cervical cancer and approximately 24 times greater to develop an advanced form of CC malignancy. Having a history of using birth control pills increase CC occurrence and aggravation (OR~2). The matrimonial status seems an important factor for CC appearance (OR = 3.58 and 2.46) among CC Tunisian patient. However, no significant biological interaction from this three joint exposure was observed in the early FIGO stages but the risk increase in advanced FIGO stages. In our Tunisian cohort, oral contraception, smoking habit and matrimonial status are associated with an overall increased risk of CC development. Indeed, it may damage the local immunity system and may affect the disease severity in patient carriers of some genetic risk biomarkers. The balance of cancer risks may vary among Tunisian CC patient, depending on some environmental co-factors.
C1 [Zidi, Sabrina] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092 Tunis, Tunisia.
[Sahli, Mariem] Charles Nicole HospitalTunis, Tunisia.
[Mezlini, Amel] Salah Azeiz Oncology InstituteTunis, Tunisia.
[Yacoubli-Loueslati, Besma] El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092 Tunis, Tunisia.
RP Zidi, S (reprint author), El Manar University, Faculty of Sciences of Tunis, Department of Biology, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092 Tunis, Tunisia.
EM ZIDISABRINA86@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 217
EP 222
DI 10.1007/s12253-018-0442-4
PG 6
ER
PT J
AU Vuletic, A
Jovanic, I
Jurisic, V
Milovanovic, Z
Nikolic, S
Spurnic, I
Konjevic, G
AF Vuletic, Ana
Jovanic, Irena
Jurisic, Vladimir
Milovanovic, Zorka
Nikolic, Srdan
Spurnic, Igor
Konjevic, Gordana
TI IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Regional lymph nodes; IL-2; IL-15; T cells; NKT-like cells; NK cells
ID Regional lymph nodes; IL-2; IL-15; T cells; NKT-like cells; NK cells
AB Regional lymph nodes (LN)s represent important immunological barriers in spreading of malignant tumors. However, they are the most frequent early metastatic site in melanoma. Immunomodulatory agents including cytokines have been included in therapy of melanoma and have shown severe side effects and toxicity. In this sense, there is a growing need for bringing these agents to further in vitro testing that may enlighten aspects of their regional application. Therefore, the aim of this study was to investigate the effect of interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of melanoma patients. In this study, we showed significant effects of IL-2 and IL-15 cytokine treatments on the expression of activating NKG2D and on inhibitory CD158a and CD158b receptors on lymphocytes, CD8+ T, NKT-like and NK cell lymphocyte subsets originating from regional LNs of melanoma patients. Furthermore, IL-2 and IL-15 by inducing the expression of NKG2D activating receptor on innate and on adaptive lymphocyte subsets and by augmenting NK cell antitumor cytotoxicity that correlated with the cytokine-induced NKG2D expression, increased antitumor potential of immune cells in regional LNs of melanoma patients irrespective of LN involvement. These findings indicate the importance of immune cell population from regional LNs of melanoma patients in the development of immune intervention strategies that may if applied locally increase antitumor potential to the level that controls tumor progressions.
C1 [Vuletic, Ana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Jovanic, Irena] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Jurisic, Vladimir] University of Kragujevac, Faculty of MedicineKragujevac, Serbia.
[Milovanovic, Zorka] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Nikolic, Srdan] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Spurnic, Igor] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
[Konjevic, Gordana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
RP Vuletic, A (reprint author), Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
EM radovanovica@ncrc.ac.rs
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 223
EP 231
DI 10.1007/s12253-018-0444-2
PG 9
ER
PT J
AU Pako, J
Bikov, A
Barta, I
Matsueda, H
Puskas, R
Galffy, G
Kerpel-Fronius, A
Antus, B
Horvath, I
AF Pako, Judit
Bikov, Andras
Barta, Imre
Matsueda, Hideyo
Puskas, Rita
Galffy, Gabriella
Kerpel-Fronius, Anna
Antus, Balazs
Horvath, Ildiko
TI Assessment of the circulating klotho protein in lung cancer patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; Biomarkers; Tumor suppressor; Premature aging; Insuline-like growth factor 1
ID Lung cancer; Biomarkers; Tumor suppressor; Premature aging; Insuline-like growth factor 1
AB The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9–486.8) vs. 383.5 (304.6–489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9–433.3 vs. 328.5 (242.5–419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4–438.5) pg/ml), squamous cell carcinoma (308 (209.6–348.1) pg/ml) and small cell lung cancer (388.8 (289.9–495.4) pg/ml). However, Tukey’s post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.
C1 [Pako, Judit] National Koranyi Institute of Pulmonology, Piheno ut 1, 1121 Budapest, Hungary.
[Bikov, Andras] Semmelweis University, Department of Pulmonology, Dios arok utca 1/c, 1125 Budapest, Hungary.
[Barta, Imre] National Koranyi Institute of Pulmonology, Piheno ut 1, 1121 Budapest, Hungary.
[Matsueda, Hideyo] Saitama Medical University Medical Center, 1981 KamodaKawagoe-shi, Saitama, Japan.
[Puskas, Rita] Semmelweis University, Department of Pulmonology, Dios arok utca 1/c, 1125 Budapest, Hungary.
[Galffy, Gabriella] Semmelweis University, Department of Pulmonology, Dios arok utca 1/c, 1125 Budapest, Hungary.
[Kerpel-Fronius, Anna] National Koranyi Institute of Pulmonology, Piheno ut 1, 1121 Budapest, Hungary.
[Antus, Balazs] National Koranyi Institute of Pulmonology, Piheno ut 1, 1121 Budapest, Hungary.
[Horvath, Ildiko] National Koranyi Institute of Pulmonology, Piheno ut 1, 1121 Budapest, Hungary.
RP Pako, J (reprint author), National Koranyi Institute of Pulmonology, 1121 Budapest, Hungary.
EM tidujok@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 233
EP 238
DI 10.1007/s12253-018-0441-5
PG 6
ER
PT J
AU Prieto-Granada, C
Castner, N
Chen, A
Li, J
Yue, B
Wong, YJ
Iyengar, S
Sondak, KV
Zager, SJ
Messina, LJ
AF Prieto-Granada, Carlos
Castner, Nicholas
Chen, Ann
Li, Jiannong
Yue, Binglin
Wong, Y Joyce
Iyengar, Sanjana
Sondak, K Vernon
Zager, S Jonathan
Messina, L Jane
TI Behavior of Cutaneous Adnexal Malignancies: a Single Institution Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cutaneous adnexal neoplasms; Eccrine carcinoma; Sentinel lymph node biopsy
ID Cutaneous adnexal neoplasms; Eccrine carcinoma; Sentinel lymph node biopsy
AB Cutaneous adnexal malignancies are biologically and pathologically diverse, and associated with a range of clinical outcomes. Given their rarity, the prognosis and optimal treatment of these neoplasms remains unclear. A single institution database from a tertiary care cancer center of patients treated for malignant cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic variables and outcome measures were analyzed in patients undergoing wide excision with or without sentinel node biopsy. 103 patients were analyzed; the majority of tumors were of eccrine sweat gland derivation (n = 69, 70%), and these exhibited a higher rate of nodal involvement and overall worse outcome. Sixteen patients (16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease at presentation and 6 who developed nodal metastasis during follow-up. 20 patients underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of nodal metastases occurred in patients with porocarcinoma. Seven patients died of disease (7%) with a median time from diagnosis to death of 48 months (range, 10–174). After a median follow up of 44.7 months, age > 70 years and larger tumor size were significantly associated with worse overall survival. Adnexal malignancies are rare tumors, and there is a paucity of information to guide the clinician in determining optimum surgical and medical treatment. Tumors of eccrine derivation, especially porocarcinomas, have a high risk of nodal involvement and may be considered for sentinel node biopsy.
C1 [Prieto-Granada, Carlos] Moffitt Cancer Center, Department of Anatomic Pathology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
[Castner, Nicholas] Moffitt Cancer Center, Department of Cutaneous OncologyTampa, FL, USA.
[Chen, Ann] Moffitt Cancer Center, Department of BiostatisticsTampa, FL, USA.
[Li, Jiannong] Moffitt Cancer Center, Department of BiostatisticsTampa, FL, USA.
[Yue, Binglin] Moffitt Cancer Center, Department of BiostatisticsTampa, FL, USA.
[Wong, Y Joyce] Moffitt Cancer Center, Department of Anatomic Pathology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
[Iyengar, Sanjana] Moffitt Cancer Center, Department of Cutaneous OncologyTampa, FL, USA.
[Sondak, K Vernon] Moffitt Cancer Center, Department of Cutaneous OncologyTampa, FL, USA.
[Zager, S Jonathan] Moffitt Cancer Center, Department of Cutaneous OncologyTampa, FL, USA.
[Messina, L Jane] Moffitt Cancer Center, Department of Anatomic Pathology, 12902 Magnolia Drive, 33612 Tampa, FL, USA.
RP Messina, LJ (reprint author), Moffitt Cancer Center, Department of Anatomic Pathology, 33612 Tampa, USA.
EM jane.messina@moffitt.org
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 239
EP 244
DI 10.1007/s12253-018-0427-3
PG 6
ER
PT J
AU Zhang, Y
Ding, Sh
Yang, J
Chen, X
Huang, W
AF Zhang, Yanping
Ding, Shi
Yang, Jie
Chen, Xingfeng
Huang, Weilin
TI Identification of miR-146a is Associated with the Aggressiveness and Suppresses Proliferation via Targeting CDKN2A in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-146a; Biomarker; Breast cancer
ID miR-146a; Biomarker; Breast cancer
AB There is emerging evidence that some microRNAs can promote or suppress several human cancer development and progression. However, the profile and molecular mechanism of microRNAs for human breast cancer is poorly unknown. We used bioinformatics approaches to find new candidate diagnostic and therapeutic miRNAs in human breast cancer via analysis of TCGA RNA sequencing data and publicly GEO microarray data, in order to provide theoretical basis for the future investigations of breast cancer. Decreased expression miR-146a was identified as a key regulator of human breast cancer development and progression. Interestingly, we founded that miR-146a expression levels dependent on tumor size and pathological grading in breast cancer patients, but not associated with other factors including age, T-classification. Kaplan-Meier survival analysis showed that patients with high miR-146a expression had a longer survival rate than those low miR-146a expressions. In vitro assays of overexpression miR-146a induces cell cycle arrest and inhibits MDA-MB-231 cell proliferation. Furthermore, luciferase reporter gene assays demonstrated that miR-146a directly combine the 3-untranslated region of CDKN2A mRNA. In conclusion, we demonstrated miR-146a play an important role in breast cancer development and progression.
C1 [Zhang, Yanping] Changde Vocational and Technical College, Department of Clinical Medicine, #4253 Renmin Road, Wuling District, 415000 Changde City, Hunan Province, China.
[Ding, Shi] Changde Vocational and Technical College, Department of Clinical Medicine, #4253 Renmin Road, Wuling District, 415000 Changde City, Hunan Province, China.
[Yang, Jie] Changde Vocational and Technical College, Department of Clinical Medicine, #4253 Renmin Road, Wuling District, 415000 Changde City, Hunan Province, China.
[Chen, Xingfeng] Changde Vocational and Technical College, Department of Clinical Medicine, #4253 Renmin Road, Wuling District, 415000 Changde City, Hunan Province, China.
[Huang, Weilin] Changde Vocational and Technical College, Department of Clinical Medicine, #4253 Renmin Road, Wuling District, 415000 Changde City, Hunan Province, China.
RP Zhang, Y (reprint author), Changde Vocational and Technical College, Department of Clinical Medicine, 415000 Changde City, China.
EM ypzhcd@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 245
EP 251
DI 10.1007/s12253-018-0430-8
PG 7
ER
PT J
AU Krafft, U
Reis, H
Ingenwerth, M
Kovalszky, I
Becker, M
Niedworok, Ch
Darr, Ch
Nyirady, P
Hadaschik, B
Szarvas, T
AF Krafft, Ulrich
Reis, Henning
Ingenwerth, Marc
Kovalszky, Ilona
Becker, Markus
Niedworok, Christian
Darr, Christopher
Nyirady, Peter
Hadaschik, Boris
Szarvas, Tibor
TI Nuclear Localization of Robo is Associated with Better Survival in Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder Cancer; Robo1; Robo4; Nuclear translocation; Slit2; Prognosis; Angiogenesis
ID Bladder Cancer; Robo1; Robo4; Nuclear translocation; Slit2; Prognosis; Angiogenesis
AB The Slit-Robo pathway has shown to be altered in several malignant diseases. However, its role in bladder cancer is poorly understood. Therefore, we aimed to assess the tissue expression of Robo1 and Robo4 as well as their ligand Slit2 in different stages of bladder cancer to explore possible changes of Slit-Robo signaling during the progression of bladder cancer. Robo1, Robo4 and Slit2 gene expressions were analyzed in 92 frozen bladder cancer tissue samples by using reverse transcription quantitative real-time PCR. Immunohistochemical analyses were performed on 149 formalin-fixed and paraffin-embedded bladder cancer tissue samples. Results were correlated with the clinical and follow-up data by performing both univariable and multivariable analyses. Robo1 and Robo4 nuclear staining intensity was significantly higher in low stage and low grade bladder cancer. Elevated Robo1 nuclear staining was associated with better disease-specific survival (DSS) (p = 0.045). Similarly, stronger Robo4 nuclear staining tended to be associated with longer DSS (p = 0.061). We found higher Robo1 and Slit2 gene expression levels in advanced stages of bladder cancer (p = 0.007 and p < 0.001). High Slit2 gene expression was correlated with significantly shorter DSS (p < 0.005), while Robo1 and Robo4 gene expressions were not associated with patients’ prognosis. Our results demonstrate that the nuclear expression of Robo1 and Robo4 is associated with a favourable prognosis suggesting that its translocation into the nucleus represent a posttranslational regulation process which may exhibit an antitumor effect in bladder cancer.
C1 [Krafft, Ulrich] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
[Reis, Henning] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Ingenwerth, Marc] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Becker, Markus] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
[Niedworok, Christian] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
[Darr, Christopher] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
[Nyirady, Peter] Semmelweis University, Department of Urology, Ulloi ut 78/b, 1082 Budapest, Hungary.
[Hadaschik, Boris] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
[Szarvas, Tibor] University of Duisburg-Essen, Department of Urology, Hufelandstr 55, 45147 Essen, Germany.
RP Szarvas, T (reprint author), University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
EM sztibusz@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 253
EP 261
DI 10.1007/s12253-018-0447-z
PG 9
ER
PT J
AU Sato, K
Miyamoto, M
Takano, M
Furuya, K
Tsuda, H
AF Sato, Kimiya
Miyamoto, Morikazu
Takano, Masashi
Furuya, Kenichi
Tsuda, Hitoshi
TI Different Prognostic Implications of Aquaporin-1 and Aquaporin-5 Expression among Different Histological Types of Ovarian Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aquaporin; Water channel; Ovarian carcinoma; Immunohistochemistry; Tissue microarray
ID Aquaporin; Water channel; Ovarian carcinoma; Immunohistochemistry; Tissue microarray
AB The aquaporins (AQPs) are a family of transmembrane water channel proteins that are distributed in various human tissues. Recent studies have suggested that AQP expression correlates with various aspects of cancer biology that determine the aggressiveness of different cancers. Ovarian carcinoma is one of the most lethal gynecological cancers. Some studies have suggested that AQPs are expressed in ovarian carcinoma, and are associated with cancer cell growth and migration. In this study, we immunohistochemically evaluated the expression of AQP1, 3, 5, and 9 in a total of 300 ovarian carcinomas using tissue microarrays. In our analyses of correlations between aquaporin expression and overall survival, high AQP5 expression was significantly associated with poorer prognosis (P = 0.029). For AQP1, the low expression group trended towards poorer prognosis than the high expression group, but the difference was not statistically significant. When ovarian carcinomas were divided by histological types, high AQP5 expression correlated with poorer prognosis in serous carcinoma (P = 0.015), and low AQP1 expression correlated with poorer prognosis in clear cell carcinomas (P = 0.0055). By contrast, high AQP1 expression correlated with poorer prognosis in mucinous carcinoma (P = 0.0001) and endometrioid carcinoma (P = 0.021). Our studies suggest that AQPs can be useful prognostic markers in ovarian carcinoma, but their correlation with prognosis depends on the histological type of ovarian carcinoma.
C1 [Sato, Kimiya] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Miyamoto, Morikazu] National Defense Medical College, Department of Obstetrics and GynecologyTokorozawa, Japan.
[Takano, Masashi] National Defense Medical College, Department of Clinical OncologyTokorozawa, Japan.
[Furuya, Kenichi] National Defense Medical College, Department of Obstetrics and GynecologyTokorozawa, Japan.
[Tsuda, Hitoshi] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
RP Sato, K (reprint author), National Defense Medical College, Department of Basic Pathology, 359-8513 Tokorozawa, Japan.
EM kimiya@ndmc.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 263
EP 271
DI 10.1007/s12253-018-0456-y
PG 9
ER
PT J
AU Li, L
Fu, LQ
Wang, HJ
Wang, YY
AF Li, Li
Fu, Luo-Qin
Wang, Hui-Ju
Wang, Yuan-Yu
TI CAP2 is a Valuable Biomarker for Diagnosis and Prognostic in Patients with Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; CAP2; Biomarker; Diagnosis; Prognosis
ID Gastric cancer; CAP2; Biomarker; Diagnosis; Prognosis
AB Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC), human breast cancer, and malignant melanoma. However, its expression in gastric cancer remains unknown, this study was to investigate CAP2 expression and its prognostic significance in gastric cancer. Firstly, we analyzed the Oncomine databases to compare CAP2 mRNA expression in gastric cancer and normal tissues. CAP2 protein expression was analyzed in gastric cancer samples and non-tumor mucosa by RT-PCR and immunohistochemical analysis. Consequently, statistical analyses were performed to evaluate the clinicopathological significance of CAP2 expression in gastric cancer. CAP2 expression was significant higher in gastric cancer tissues than that in non-tumor mucosa at protein levels. CAP2 was up-regulated in 57.8% (252/436) of gastric cancer samples, while detected in only 10.9% (10/92) of non-tumor mucosa. Statistical analysis shows that the expression of CAP2 was correlated with tumor size, Lauren’s classification, depth of invasion, lymph node and distant metastases, and regional lymph node stage, TNM stage, but not with age, sex, histology classification, and histologic differentiation. Kaplan-Meier analysis indicated that high CAP2 expression was associated with poor overall survival (78.7%) in 203 of 252 gastric cancer patients. In stage I, II, and III tumors, the 5-year survival rate was lower in those with high expression of CAP2 than those with low expression. In stage IV tumors, the expression of CAP2 did not correlate with the 5-year survival rate. Multiple Cox regression analysis indicated CAP2 as an independent predictor for overall survival [hazard ratio (HR) = 2.045, 95% confidence interval: 1.445–2.895, p < 0.01], while Lauren’s classification, TNM stage, and expression of CAP2 were independent prognostic factors in patients with gastric cancer. For the first time, we found that CAP2 was upregulated in gastric cancer, and was associated with lymph node and distant metastases. CAP2 may serve as a prognostic indicator for patients with gastric cancer.
C1 [Li, Li] People’s Hospital of Hangzhou Medical College, Zhejiang Provincial People’s Hospital, Clinical Research Institute, 310014 Hangzhou, Zhejiang, China.
[Fu, Luo-Qin] People’s Hospital of Hangzhou Medical College, Zhejiang Provincial People’s Hospital, Clinical Research Institute, 310014 Hangzhou, Zhejiang, China.
[Wang, Hui-Ju] People’s Hospital of Hangzhou Medical College, Zhejiang Provincial People’s Hospital, Clinical Research Institute, 310014 Hangzhou, Zhejiang, China.
[Wang, Yuan-Yu] Key Laboratory of Gastroenterology of Zhejiang ProvinceHangzhou, Zhejiang, China.
RP Wang, YY (reprint author), Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, China.
EM lywyy1979@126.com
CR Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J, 2016, Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 273
EP 279
DI 10.1007/s12253-018-0450-4
PG 7
ER
PT J
AU Liu, M
Du, K
Jiang, B
Wu, X
AF Liu, Maoxi
Du, Kunli
Jiang, Bo
Wu, Xingye
TI High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancer; PLD2; Proliferation; NF-κBp65; Hypoxia
ID Colon cancer; PLD2; Proliferation; NF-κBp65; Hypoxia
AB Hypoxia is a typical feature of colon cancer occurrence and progression. We have reported that high expression and activity of PhospholipaseD2 (PLD2) induced by hypoxia in colon cancer cells. In order to further investigate the role of PLD2 in colon cancer under hypoxic conditions. MTT assay was used to detect the proliferation of human colon cancer cells (SW480 and SW620) under hypoxic conditions by decrease the PLD2 gene expression or inhibit the activity of PLD2. Expression level of p-P65/T-P65 and Cyclin D1 were detected in those cells treated as above through using western blot and RT-PCR analysis. Effect of NF-κBp65 inhibitor (BAY-117082) on the proliferation and expression level of Cyclin D1 and PLD2 of colon cancer cells under hypoxic conditions were further analyzed. As a result, decreased the expression of PLD2 or inhibited the activity of PLD2 leaded to the proliferation of hypoxia colon cancer cells reduced, and along with the expression level of p-P65/T-P65 and Cyclin D1 reduced. However, inhibition the expression level of p-P65/T-P65 lead to the proliferation and expression of Cyclin D1 in those hypoxia colon cancer cells also reduced. In vivo growth decreased in response to PLD2 and NF-κBp65 inhibition. Our study indicates that high expression of PLD2 induced by hypoxia promotes the proliferation of colon cancer cells, and it may elevate the expression level of Cyclin D1 through activating NF-κBp65 signaling pathway. Inhibition of the PLD2 expression may provide a new clue for treatment for colon cancer.
C1 [Liu, Maoxi] Shanxi Cancer Hospital, Department of Anorectal Surgery, 030013 Taiyuan, China.
[Du, Kunli] Xijing Hospital, Department of Anorectal Surgery, 710032 Xi’an, China.
[Jiang, Bo] Shanxi Cancer Hospital, Department of Anorectal Surgery, 030013 Taiyuan, China.
[Wu, Xingye] The First Affiliated Hospital of Chongqing Medical University, Department of Gastrointestinal Surgery, 400016 Chongqing, China.
RP Jiang, B (reprint author), Shanxi Cancer Hospital, Department of Anorectal Surgery, 030013 Taiyuan, China.
EM 13834567839@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 281
EP 290
DI 10.1007/s12253-018-0429-1
PG 10
ER
PT J
AU Kiss, K
Regos, E
Rada, K
Firneisz, G
Baghy, K
Kovalszky, I
AF Kiss, Katalin
Regos, Eszter
Rada, Kristof
Firneisz, Gabor
Baghy, Kornelia
Kovalszky, Ilona
TI Chronic Hyperglycaemia Induced Alterations of Hepatic Stellate Cells Differ from the Effect of TGFB1, and Point toward Metabolic Stress
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hyperglycaemia; TGFB1; Hepatic stellate cells; Fibrogenesis; Endoplasmic stress
ID Hyperglycaemia; TGFB1; Hepatic stellate cells; Fibrogenesis; Endoplasmic stress
AB The deleterious effect of hyperglycemia on the biology of the liver is supported by clinical evidence. It can promote the development of fatty liver, liver fibrosis, even liver cancer as complication of diabetes mellitus. As liver fibrosis is the consequence of hepatic stellate cell (HSC) activation, the questions were addressed whether alterations induced by high glucose concentration are directly related to TGFB1 effect, or other mechanisms are activated. In order to obtain information on the response of HSC for high glucose, LX-2 cells (an immortalized human HSC cell lineage) were cultured in 15.3 mM glucose containing medium for 21 days. The effect of glucose was compared to that of TGFB1. Our data revealed that chronic exposure of high glucose concentration initiated profound alteration of LX-2 cells and the effect is different from those observed upon interaction with TGFB1. Whereas TGFB1 induced the production of extracellular matrix proteins, high glucose exposure resulted in decreased MMP2 activity, retardation of type I collagen in the endoplasmic reticulum, with decreased pS6 expression, pointing to development of endoplasmic stress and sequestration of p21CIP1/WAF1 in the cytoplasm which can promote the proliferation of LX2 cells.
C1 [Kiss, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Regos, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Rada, Kristof] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Firneisz, Gabor] Semmelweis University, 2nd Department of Internal Medicine, Szentkiralyi utca 46, H-1085 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM koval@korb1.sote.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 291
EP 299
DI 10.1007/s12253-018-0458-9
PG 9
ER
PT J
AU Li, Z
Zhang, B
You, W
Li, P
Youlin, K
AF Li, Zhang
Zhang, Bingqiang
You, Wenxian
Li, Pan
Youlin, Kuang
TI Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-β Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma cell; Rab23; Rac1; TGF-β; Migration
ID Hepatocellular carcinoma cell; Rab23; Rac1; TGF-β; Migration
AB Rab23 is a member of Ras-related small GTPase family, which plays a critical role in the progression of wide range of tumors. However, its biological function in hepatocellular carcinoma still remains unclear. Here, we investigated the effects of Rab23 on proliferation and migration in hepatocellular carcinoma cell and its potential mechanisms. We found over-expression of Rab23 promoted the Hep3B hepatocellular carcinoma cell migration, which could be reversed by Rab23 silencing. Rab23 induced Rac1 activation and followed progression of epithelial-mesenchymal transition (EMT) along with upregulation of N-cadherin, snail as well as vimentin and downregulation of E-cadherin via upregulating Transforming Growth Factor-β (TGF-β). Silencing Rac1 significantly attenuated Rab23-induced HepG2 migration and TGF-β. Moreover, knockdown of TGF-β effectively attenuated Rab23-induced EMT. Taken together, we demonstrated a mechanistic cascade of Rab23 enhancing Rac1 activation and subsequent TGF-β expression, leading to hepatocellular carcinoma cell migration.
C1 [Li, Zhang] The First Affiliated Hospital of Chongqing Medical University, Gastroenterology, 400016 Chongqing, China.
[Zhang, Bingqiang] The First Affiliated Hospital of Chongqing Medical University, Gastroenterology, 400016 Chongqing, China.
[You, Wenxian] The First Affiliated Hospital of Chongqing Medical University, Gastroenterology, 400016 Chongqing, China.
[Li, Pan] The First Affiliated Hospital of Chongqing Medical University, Gastroenterology, 400016 Chongqing, China.
[Youlin, Kuang] Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
RP Youlin, K (reprint author), Chongqing Medical University, The First Affiliated Hospital, Department of Urology, 400016 Chongqing, China.
EM kyl361@163.com
CR Massarweh NN, El-Serag HB, 2017, Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control 24:1073274817729245
Forner A, Llovet JM, Bruix J, 2012, Hepatocellular carcinoma. In: Lancet, vol 379,, London), pp 1245–1255
Delevoye C, Goud B, 2015, Rab GTPases and kinesin motors in endosomal trafficking. Methods Cell Biol 130:235–246
Eggenschwiler JT, Espinoza E, Anderson KV, 2001, Rab23 is an essential negative regulator of the mouse sonic hedgehog signalling pathway. Nature 412:194–198
Cai ZZ, Xu LB, Cai JL, Wang JS, Zhou B, Hu H, 2015, Inactivation of Rab23 inhibits the invasion and motility of pancreatic duct adenocarcinoma. Genet Mol Res 14:2707–2715
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Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K, Cross D, Tan LK, Tao J, Gopalakrishnan V, Tang BL, Kon OL, Tan P, 2008, Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res 68:4623– 4630
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Jian Q,Miao Y, Tang L, HuangM, Yang Y, BaW, Liu Y, Chi S, Li C, 2016, Rab23 promotes squamous cell carcinoma cell migration and invasion via integrin beta1/Rac1 pathway. Oncotarget 7:5342– 5352
Zhang XY,Mu JH, Liu LY, Zhang HZ, 2017, Upregulation of miR- 802 suppresses gastric cancer oncogenicity via targeting RAB23 expression. Eur Rev Med Pharmacol Sci 21:4071–4078
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Wendt MK, Tian M, Schiemann WP, 2012, Deconstructing the mechanisms and consequences of TGF-beta-induced EMT during cancer progression. Cell Tissue Res 347:85–101
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 301
EP 306
DI 10.1007/s12253-018-0463-z
PG 6
ER
PT J
AU Yang, Sh
Liu, L
Xu, D
Li, X
AF Yang, Shasha
Liu, Lan
Xu, Dongyuan
Li, Xiangdan
TI The Relationship of the TLR9 and TLR2 Genetic Polymorphisms with Cervical Cancer Risk: a Meta-Analysis of Case-Control Studies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TLR9; TLR2; Meta-analysis; Cervical cancer; Polymorphism
ID TLR9; TLR2; Meta-analysis; Cervical cancer; Polymorphism
AB This meta-analysis aimed to assess the association of common TLR9 and TLR2 gene polymorphisms (TLR9 1486 T/C, TLR9 G2848A, and TLR2–196 to −174 del/ins) with cervical cancer risk. Studies were searched in Scopus, Pubmed, Embase, and CNKI until December 2017. Both fixed-effects and random-effects models were applied to combine odds ratio (OR) and 95% confidence intervals (95% CI). A total of 11 studies including 7856 participants were identified. The pooled estimation revealed an increased risk of cervical cancer in Caucasian subjects carrying the C allele of the TLR9 1486 T/C polymorphism (OR = 1.46, 95% CI: 1.11–1.92, p = 0.007), while there was a decreased risk in Mixed subjects carrying the C allele (OR = 0.35, 95% CI: 0.15–0.82, p = 0.016). Concerning the TLR9 G2848A polymorphism, the A allele was associated with an increased risk of cervical cancer in Caucasians (OR = 1.19, 95% CI: 1.02–1.40, p = 0.030), whereas Asian and Mixed subjects showed no significant associations. No significant associations were demonstrated between the TLR2–196 to −174 del/ins polymorphism and cervical cancer. Our findings suggest that the TLR9 1486 T/C and G2848A polymorphisms contribute to cervical cancer risk, but there is no association of the TLR2–196 to −174 del/ins polymorphism with cervical cancer.
C1 [Yang, Shasha] Medical College of Yanbian University, Center of Morphological Experiment, 133000 Yanji, China.
[Liu, Lan] Affiliated Hospital of Yanbian University, Department of Pathology, 133000 Yanji, China.
[Xu, Dongyuan] Medical College of Yanbian University, Center of Morphological Experiment, 133000 Yanji, China.
[Li, Xiangdan] Medical College of Yanbian University, Center of Morphological Experiment, 133000 Yanji, China.
RP Li, X (reprint author), Medical College of Yanbian University, Center of Morphological Experiment, 133000 Yanji, China.
EM lixiangdan@ybu.edu.cn
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
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Hasimu A, Ge L, Li QZ, Zhang RP, Guo X, 2011, Expressions of toll-like receptors 3, 4, 7, and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women. Chin J Cancer 30(5):344–350
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 307
EP 315
DI 10.1007/s12253-018-0465-x
PG 9
ER
PT J
AU Balatoni, T
Ladanyi, A
Frohlich, G
Czirbesz, K
Kovacs, P
Panczel, G
Bence, E
Plotar, V
Liszkay, G
AF Balatoni, Timea
Ladanyi, Andrea
Frohlich, Georgina
Czirbesz, Kata
Kovacs, Peter
Panczel, Gitta
Bence, Eszter
Plotar, Vanda
Liszkay, Gabriella
TI Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Ipilimumab; Predictive factors; Lactate dehydrogenase
ID Melanoma; Ipilimumab; Predictive factors; Lactate dehydrogenase
AB Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17%of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225–10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.
C1 [Balatoni, Timea] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gy. u., H-1122 Budapest, Hungary.
[Ladanyi, Andrea] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Frohlich, Georgina] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Czirbesz, Kata] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gy. u., H-1122 Budapest, Hungary.
[Kovacs, Peter] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gy. u., H-1122 Budapest, Hungary.
[Panczel, Gitta] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gy. u., H-1122 Budapest, Hungary.
[Bence, Eszter] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Plotar, Vanda] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of Dermatology, 7-9. Rath Gy. u., H-1122 Budapest, Hungary.
RP Balatoni, T (reprint author), National Institute of Oncology, Department of Dermatology, H-1122 Budapest, Hungary.
EM balatoni.timea@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 317
EP 325
DI 10.1007/s12253-018-0466-9
PG 9
ER
PT J
AU Inomata, M
Hirai, T
Seto, Z
Tokui, K
Taka, Ch
Okazawa, S
Kambara, K
Ichikawa, T
Imanishi, Sh
Yamada, T
Miwa, T
Hayashi, R
Tobe, K
AF Inomata, Minehiko
Hirai, Takahiro
Seto, Zenta
Tokui, Kotaro
Taka, Chihiro
Okazawa, Seisuke
Kambara, Kenta
Ichikawa, Tomomi
Imanishi, Shingo
Yamada, Toru
Miwa, Toshiro
Hayashi, Ryuji
Tobe, Kazuyuki
TI Clinical Parameters for Predicting the Survival in Patients with Squamous and Non-squamous-cell NSCLC Receiving PD-1 Inhibitor Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Programmed death 1 inhibitor; Squamous cell lung cancer
ID Non-small cell lung cancer; Programmed death 1 inhibitor; Squamous cell lung cancer
AB We explored the associations between progression-free survival (PFS) after the initiation of PD-1 inhibitor therapy and the clinical parameters in patients with NSCLC. We reviewed the clinical data of patients with NSCLC treated with PD-1 inhibitor. Data of a total of 36 patients, including 16 patients with squamous cell NSCLC and 20 patients with non-squamous cell NSCLC were reviewed. Multivariate analyses identified EGFR status, C-reactive protein (CRP), and PFS following previous therapy as being significantly associated with the PFS after initiation of PD-1 inhibitor therapy in patients with NSCLC. In patients with squamous cell NSCLC, the blood neutrophil/lymphocyte ratio (NLR), serum lactate dehydrogenase (LDH), serum C-reactive protein (CRP), and PFS following previous therapy were identified as being significantly associated with the PFS after initiation of PD-1 inhibitor therapy. However, none of these associations, except for PFS following previous therapy, were found in patients with non-squamous cell NSCLC. NLR, LDH and CRP were associated with the PFS after initiation of PD-1 inhibitor therapy in patients with squamous cell NSCLC, and PFS following previous therapy was the common parameter associated with the PFS after initiation of PD-1 inhibitor therapy in both squamous-cell NSCLC and non-squamous-cell NSCLC patients.
C1 [Inomata, Minehiko] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Hirai, Takahiro] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Seto, Zenta] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Tokui, Kotaro] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Taka, Chihiro] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Okazawa, Seisuke] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Kambara, Kenta] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Ichikawa, Tomomi] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Imanishi, Shingo] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Yamada, Toru] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Miwa, Toshiro] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
[Hayashi, Ryuji] Toyama University Hospital, Department of Medical OncologyToyama City, Japan.
[Tobe, Kazuyuki] Toyama University Hospital, First Department of Internal Medicine, Sugitani 2630, 930-0194 Toyama City, Japan.
RP Inomata, M (reprint author), Toyama University Hospital, First Department of Internal Medicine, 930-0194 Toyama City, Japan.
EM minomata@med.u-toyama.ac.jp
CR Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR, 2015, Nivolumab versus docetaxel in advanced squamous-cell nonsmall- cell lung cancer. N Engl J Med 373:123–135
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Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D, Ponce S, Ares LP, Leroy L, Audigier-Valette C, Felip E, Zeron- Medina J, Garrido P, Brosseau S, Zalcman G, Mazieres J, Caramela C, Lahmar J, Adam J, Chaput N, Soria JC, Besse B, 2018, Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced nonsmall cell lung cancer. JAMA Oncol 4:351–357
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Kobayashi H, Omori S, Nakashima K, Wakuda K, Ono A, Kenmotsu H, Naito T, Murakami H, Endo M, Takahashi T, 2017, Response to the treatment immediately before nivolumab monotherapy may predict clinical response to nivolumab in patients with non-small cell lung cancer. Int J Clin Oncol 22(4):690–697
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Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW, 2011, The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105: 93–103
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 327
EP 333
DI 10.1007/s12253-018-0473-x
PG 7
ER
PT J
AU Eftekhari, A
Peivand, Z
Saadat, I
Saadat, M
AF Eftekhari, Alireza
Peivand, Zahra
Saadat, Iraj
Saadat, Mostafa
TI Association between Genetic Polymorphisms in Superoxide Dismutase Gene Family and Risk of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; SOD1; SOD2; SOD3; Polymorphism
ID Gastric cancer; SOD1; SOD2; SOD3; Polymorphism
AB To determine the association between the SOD1 (Ins/Del), SOD2 (rs2758339, rs5746136), and SOD3 (rs2536512) polymorphisms and the risk of gastric cancer the present study performed. This is a case-control study, including 159 patients with gastric cancer and 242 healthy controls. All subjects were Persian Muslims living in Shiraz (south west Iran). Frequency matching by age and gender was performed. Genomic DNA was extracted from whole blood. Genotypes of the study polymorphism were determined using polymerase chain reaction based methods. The SOD1 Ins/Del and SOD3 rs2536512 polymorphisms did not appear to have relationship with gastric cancer risk. Both SOD2 polymorphisms (rs2758339, rs5746136) showed significant association with the risk of gastric cancer, under assumption that the variant alleles act as dominant alleles. There was significant association between smoking habit and the risk of gastric cancer (OR = 2.54, 95% CI = 1.61–4.02, P < 0.001). Smoker individuals having two putative high-risk genotypes showed elevated risk of gastric cancer compared with nonsmokers without high-risk genotypes, (OR = 5.75, 95% CI = 1.59–20.6, P = 0.007). Assuming that smoking habit and the genotypes are independent risk factors, there was a significant linear trend for the numbers of risk factors and gastric cancer risk (χ2 = 22.9, P < 0.001). This study indicates that the SOD2 polymorphism (rs2758339, rs5746136) is associated with increased risk of gastric cancer, especially in smoker individuals.
C1 [Eftekhari, Alireza] Shiraz University, College of Sciences, Department of Biology, 71467-13565 Shiraz, Iran.
[Peivand, Zahra] Shiraz University, College of Sciences, Department of Biology, 71467-13565 Shiraz, Iran.
[Saadat, Iraj] Shiraz University, College of Sciences, Department of Biology, 71467-13565 Shiraz, Iran.
[Saadat, Mostafa] Shiraz University, College of Sciences, Department of Biology, 71467-13565 Shiraz, Iran.
RP Saadat, I (reprint author), Shiraz University, College of Sciences, Department of Biology, 71467-13565 Shiraz, Iran.
EM isaadat@shirazu.ac.ir
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 335
EP 339
DI 10.1007/s12253-018-0470-0
PG 5
ER
PT J
AU Rosenberg, EJ
Albersheim, AJ
Sathianathen, JN
Murugan, P
Weight, JCh
AF Rosenberg, E Joel
Albersheim, A Jacob
Sathianathen, J Niranjan
Murugan, Paari
Weight, J Christopher
TI Five New Cases of Primary Renal Carcinoid Tumor: Case Reports and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urology; Oncology; Kidney; Renal; Carcinoid; Neuroendocrine; Surgical pathology
ID Urology; Oncology; Kidney; Renal; Carcinoid; Neuroendocrine; Surgical pathology
AB Carcinoid tumors, a slow-growing NET, most commonly arise in the gastrointestinal tract (73.7%), followed by the bronchopulmonary system (25.1%), and least commonly in the genitourinary system (<1%). Primary carcinoid tumors of the kidney—with approximately 100 cases reported in the literature since the first described case in 1966—are thought to be so rare because neuroendocrine cells are not typically found in the renal parenchyma. Here we present a series of five cases at our institution with primary carcinoid tumors of the kidney followed by a literature review. In the literature we describe the diagnostic stains used to determine renal carcinoid tumors. We also describe why partial nephrectomies are the gold standard treatment in these cases, while radical nephrectomy can be used in certain circumstances. Limited research on treatment of metastasis of these tumors exists, but we summarize the results of existing treatments. Major prognostic factors and survival of patients with these tumors is described as well as the increased prevalence of this tumors in patients with horseshoe kidneys. This study presents five new cases of primary renal carcinoid tumors and a comprehensive review of the previously published cases.We are able to make limited prognostic predictions from currently published literature, but we will continue to learn from our patients’ long-term courses to draw conclusions about biological behavior, treatment outcomes, and recurrence of rare disease.
C1 [Rosenberg, E Joel] University of Minnesota Medical School, Department of Urology, 420 Delaware St. SE MMC 394, 55455 Minneapolis, MN, USA.
[Albersheim, A Jacob] University of Minnesota Medical School, Department of Urology, 420 Delaware St. SE MMC 394, 55455 Minneapolis, MN, USA.
[Sathianathen, J Niranjan] University of Minnesota Medical School, Department of Urology, 420 Delaware St. SE MMC 394, 55455 Minneapolis, MN, USA.
[Murugan, Paari] University of Minnesota Medical School, Department of Urology, 420 Delaware St. SE MMC 394, 55455 Minneapolis, MN, USA.
[Weight, J Christopher] University of Minnesota Medical School, Department of Urology, 420 Delaware St. SE MMC 394, 55455 Minneapolis, MN, USA.
RP Weight, JCh (reprint author), University of Minnesota Medical School, Department of Urology, 55455 Minneapolis, USA.
EM cjweight@umn.edu
CR Sun K, You Q, Zhao M, Yao H, Xiang H, Wang L, 2013, Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature. Int J Clin Exp Pathol 6(11):2578–2584
Seker KG, Sam E, Sahin S et al, 2017, Partial nephrectomy in horseshoe kidney: primary carcinoid tumor. Arch Ital Urol Androl 89(4):316–318
Korkmaz T, Seber S, Yavuzer D, Gumus M, Turhal NS, 2013, Primary renal carcinoid: treatment and prognosis. Crit Rev Oncol Hematol 87(3):256–264
Resnick ME, Unterberger H, McLoughlin PT, 1966, Renal carcinoid producing the carcinoid syndrome.Med Times 94(8):895–896
Litwinowicz R, Szpor J, Janus G, Worek M, Okon K, 2011, Primary carcinoid tumour in horseshoe kidney. Pol J Pathol 62(1): 72–74
Omiyale AO, Venyo AK, 2013, Primary carcinoid tumour of the kidney: a review of the literature. Adv Urol 2013:579396
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Romero FR, Rais-Bahrami S, Permpongkosol S, Fine SW, Kohanim S, Jarrett TW, 2006, Primary carcinoid tumors of the kidney. J Urol 176(6 Pt 1):2359–2366
Singh PP, Malhotra AS, Kashyap V, 2009, Carcinoid tumor of the kidney: an unusual renal tumor. Indian J Urol 25(4):537–538
Gedaly R, Jeon H, Johnston TD, McHugh PP, RowlandRG, Ranjan D, 2008, Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis. World J Surg Oncol 6:41
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Krishnan B, Truong LD, Saleh G, SirbaskuDM, SlawinKM(1997, Horseshoe kidney is associated with an increased relative risk of primary renal carcinoid tumor. J Urol 157(6):2059–2066
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 341
EP 346
DI 10.1007/s12253-018-0481-x
PG 6
ER
PT J
AU Koo, DH
Do, IG
Oh, S
Lee, YGy
Kim, K
Sohn, HJ
Park, SK
Yang, HJ
Jung, SY
Park, ID
Jeong, UK
Kim, OH
Kim, H
Serrero, G
Chun, HK
AF Koo, Dong-Hoe
Do, In-Gu
Oh, Sukjoong
Lee, Yun-Gyoo
Kim, Kyungeun
Sohn, Hee Jin
Park, Soo-Kyung
Yang, Hyo-Joon
Jung, Suk Yoon
Park, Il Dong
Jeong, Uk Kyung
Kim, Ook Hyung
Kim, Hungdai
Serrero, Ginette
Chun, Ho-Kyung
TI Prognostic Value of Progranulin in Patients with Colorectal Cancer Treated with Curative Resection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Progranulin; Colorectal neoplasms; Recurrence; Prognosis
ID Progranulin; Colorectal neoplasms; Recurrence; Prognosis
AB Progranulin (PGRN) has been characterized as an autocrine growth and survival factor and is known to stimulate tumorigenesis and proliferation of several types of cancer cell. However, little is known about the prognostic role of PGRN in colorectal cancer (CRC). A retrospective analysis was performed for patients with colorectal cancer who underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semi-quantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+), and high expression was considered for tumors graded ≥2+ staining intensity. A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. Thirty-eight patients (35%) had tumors with high PGRN expression, and there was a trend of elevated pre-operative CEA and CA19–9 levels in patients with high PGRN expressing tumors compared to those with low PGRN-expressing tumors (CEA, 49% vs. 21%; CA19–9, 21% vs. 7%). The 3–year recurrence-free survival (3Y–RFS) and overall survival rates were 83.7%(95% CI, 76.8–90.6) and 96.0%(95% CI, 92.3–99.7), respectively. Patients with high PGRN-expressing tumors had a worse rate of 3Y–RFS (66.8%) compared to those with low PGRN-expressing tumors (92.4%; p = 0.010). Multivariate analysis showed that high PGRN expression, age (>66 years), stage (III), and perineural invasion (+) were independent prognostic factors associated with poor RFS after adjusting for confounding factors including sex, MSI, tumor location, KRAS, and lympho-vascular invasion. PGRN overexpression was significantly associated with poor RFS in patients with CRC who have undergone curative resection.
C1 [Koo, Dong-Hoe] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Hematology/Oncology, Department of Internal Medicine, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Do, In-Gu] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of PathologySeoul, South Korea.
[Oh, Sukjoong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Hematology/Oncology, Department of Internal Medicine, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Lee, Yun-Gyoo] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Hematology/Oncology, Department of Internal Medicine, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Kim, Kyungeun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of PathologySeoul, South Korea.
[Sohn, Hee Jin] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of PathologySeoul, South Korea.
[Park, Soo-Kyung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Gastroenterology, Department of Internal MedicineSeoul, South Korea.
[Yang, Hyo-Joon] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Gastroenterology, Department of Internal MedicineSeoul, South Korea.
[Jung, Suk Yoon] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Gastroenterology, Department of Internal MedicineSeoul, South Korea.
[Park, Il Dong] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Gastroenterology, Department of Internal MedicineSeoul, South Korea.
[Jeong, Uk Kyung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Surgery, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Kim, Ook Hyung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Surgery, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Kim, Hungdai] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Surgery, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
[Serrero, Ginette] A&G Pharmaceutical, Inc.Columbia, MD, USA.
[Chun, Ho-Kyung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Surgery, 29 Saemunan-ro, Jongno-gu, 03181 Seoul, South Korea.
RP Oh, S (reprint author), Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Division of Hematology/Oncology, Department of Internal Medicine, 03181 Seoul, South Korea.
EM sukjoong.oh@samsung.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 343
EP 350
DI 10.1007/s12253-018-0520-7
PG 8
ER
PT J
AU Argyropoulou, M
Veskoukis, SA
Karanatsiou, PM
Manolakelli, A
Kostoglou-Athanassiou, I
Vilaras, G
Karameris, A
Liadaki, K
AF Argyropoulou, Marilena
Veskoukis, S Aristidis
Karanatsiou, Pagona-Maria
Manolakelli, Aikaterini
Kostoglou-Athanassiou, Ifigenia
Vilaras, George
Karameris, Andreas
Liadaki, Kalliopi
TI Low Prevalence of TERT Promoter, BRAF and RAS Mutations in Papillary Thyroid Cancer in the Greek Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TERT; BRAF; RAS; Mutations; Papillary thyroid cancer
ID TERT; BRAF; RAS; Mutations; Papillary thyroid cancer
AB Thyroid cancer is a common endocrine malignancy and displays a variety of histological patterns ranging from adenoma to malignant tumors. Molecular diagnostics have given significant insights into the genetic basis of thyroid tumorigenesis, known to be linked with signaling pathways affected by oxidative stress. We report for the first time a genotype study of TERT promoter combined with BRAF and RAS mutations in Papillary Thyroid Cancer (PTC) cases in the Greek population. Polymerase Chain Reaction and sequencing were used to identify TERT promoter (C228T, C250T, CC243-243TT) mutations, the BRAF (T1799A) mutation and mutations in codons 12, 13, 61 of the HRAS, KRAS and NRAS genes. The most common C228T TERT promoter mutation was identified in 2 PTC cases co-existing with the BRAF mutation. The BRAF T1799A mutation was detected in 10 PTC cases, while two different NRAS mutations in codon 61 (C181A and A182G) were found in 2 PTC cases. These mutations occur in a mutually exclusive manner. Our results indicate that despite the low frequencies, the study of the specific mutations should be encouraged because they are indicative of aggressive forms of thyroid cancer of the papillary histotype in this patient cohort, thus providing insights towards their therapeutic management.
C1 [Argyropoulou, Marilena] University of Thessaly, Department of Biochemistry and Biotechnology, Viopolis, Mezourlo, 41500 Larissa, Greece.
[Veskoukis, S Aristidis] University of Thessaly, Department of Biochemistry and Biotechnology, Viopolis, Mezourlo, 41500 Larissa, Greece.
[Karanatsiou, Pagona-Maria] University of Thessaly, Department of Biochemistry and Biotechnology, Viopolis, Mezourlo, 41500 Larissa, Greece.
[Manolakelli, Aikaterini] University of Thessaly, Department of Biochemistry and Biotechnology, Viopolis, Mezourlo, 41500 Larissa, Greece.
[Kostoglou-Athanassiou, Ifigenia] General Hospital Korgialenio-Benakio National Red Cross, Department of Endocrinology, Erythrou Stavrou 1, 11526 Athens, Greece.
[Vilaras, George] 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of Pathology, Section of Molecular Pathology, Monis Petraki 10, 11521 Athens, Greece.
[Karameris, Andreas] 417 Veterans Administration Hospital (Ν.Ι.Μ.Τ.S.), Department of Pathology, Section of Molecular Pathology, Monis Petraki 10, 11521 Athens, Greece.
[Liadaki, Kalliopi] University of Thessaly, Department of Biochemistry and Biotechnology, Viopolis, Mezourlo, 41500 Larissa, Greece.
RP Liadaki, K (reprint author), University of Thessaly, Department of Biochemistry and Biotechnology, 41500 Larissa, Greece.
EM kliad@bio.uth.gr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 347
EP 354
DI 10.1007/s12253-018-0497-2
PG 8
ER
PT J
AU Yang, X
Liu, G
Zang, L
Li, D
Yu, F
Xiang, X
Li, W
AF Yang, Xiaolin
Liu, Geling
Zang, Luyang
Li, Ding
Yu, Fang
Xiang, Xiuxiu
Li, Weijuan
TI ZNF703 is Overexpressed in Papillary Thyroid Carcinoma Tissues and Mediates K1 Cell Proliferation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ZNF703; Papillary thyroid cancer; siRNA; Proliferation; Apoptosis; Invasion
ID ZNF703; Papillary thyroid cancer; siRNA; Proliferation; Apoptosis; Invasion
AB Zinc finger protein 703 (ZNF703), a member of the NET family of transcription factors, has recently emerged as an important player in the development of several types of cancers, though its role in papillary thyroid cancer (PTC) has not been characterized. We investigated the expression of ZNF703, its association with the most common genetic mutation in PTC, BRAF V600E, and its potential use as a therapeutic target. Real-time PCR, immunohistochemical staining, and western blot analysis of ZNF703 expression were performed for 36 cases of PTC and corresponding normal thyroid tissues. ZNF703 mRNA and protein expression was found to be significantly higher in PTC compared to normal thyroid tissues (P < 0.05). Furthermore, expression was associated with the tumor size, lymph node metastasis, and advanced disease stage. Immunohistochemical results showed that there was no correlation between ZNF703 protein levels and BRAF V600E mutation. The human PTC cell line K1, which has a BRAF V600E mutation, was selected for further investigation. Using small interfering RNA (siRNA), ZNF703 was shown to contribute to the proliferation, apoptosis, and invasion of K1 cells. ZNF703-siRNA downregulated E2F1 and MMP9 protein expression and enhanced the expression of p27 protein (P < 0.05), but had no effects on BRAF V600E protein levels. These results suggest that ZNF703 may be of potential use as a new marker for PTC prognosis and therapy that functions independent of BRAF V600E expression.
C1 [Yang, Xiaolin] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Liu, Geling] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Zang, Luyang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Ding] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Yu, Fang] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Xiang, Xiuxiu] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
[Li, Weijuan] Tangshan Workers Hospital, Department of Endocrinology (Section I)Tangshan, China.
RP Liu, G (reprint author), Tangshan Workers Hospital, Department of Endocrinology (Section I), Tangshan, China.
EM tsliugeling@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 355
EP 364
DI 10.1007/s12253-018-0494-5
PG 10
ER
PT J
AU Zhang, G
Xu, Y
Zhou, H
AF Zhang, Geng
Xu, Yi
Zhou, Huifang
TI The Infiltration of ICOS+ Cells in Nasopharyngeal Carcinoma is Beneficial for Improved Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nasopharyngeal carcinoma; Survival; Inducible T cell co-stimulator; IFNγ; Prognosis
ID Nasopharyngeal carcinoma; Survival; Inducible T cell co-stimulator; IFNγ; Prognosis
AB Nasopharyngeal carcinoma (NPC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. Currently, immune checkpoint therapy has brought new treatment strategy for NPC. The inducible T cell co-stimulator (ICOS) belongs to the B7-CD28 immunoglobulin superfamily, which is currently the subject of intense study due to great successes gained in treatment of different malignancies by disrupting their family members. However, the role of ICOS played in NPC remains poorly understood. Immunohistochemistry (IHC) was stained with the ICOS specific antibody and ICOS expression is decreased in patients with either lymphatic or distant metastasis and inversely associated with TNM stage of NPC patients. Importantly, high ICOS expression is significantly correlated with overall survival (OS) of NPC patients (N = 185, p < 0.001), and ICOS expression is also proved to be an independent prognostic factor by multivariate analysis. Surgical excised fresh NPC specimens (N = 185) were homogenized to analyze the specific cytokine expression by ELISA assay. ICOS expression level is associated with increased cytotoxic T lymphocyte number and high interferon IFNγ expression, the characteristics of Th1 cells. In addition, the correlation between the percentage of ICOS+ T cells in tumor tissue and survival was detected. Conclusively, expression of ICOS is associated with improved survival in NPC and percentage of ICOS+ cells acting as Th1 cells in primary tumor tissue may be a clinical biomarker for good prognosis of NPC patients.
C1 [Zhang, Geng] Tianjin Medical University General Hospital, Department of Otorhinolaryngology, No. 154 Anshan Road, Heping District, 300052 Tianjin, China.
[Xu, Yi] Tianjin Medical University General Hospital, Department of Otorhinolaryngology, No. 154 Anshan Road, Heping District, 300052 Tianjin, China.
[Zhou, Huifang] Tianjin Medical University General Hospital, Department of Otorhinolaryngology, No. 154 Anshan Road, Heping District, 300052 Tianjin, China.
RP Zhou, H (reprint author), Tianjin Medical University General Hospital, Department of Otorhinolaryngology, 300052 Tianjin, China.
EM huifzhou667@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 365
EP 370
DI 10.1007/s12253-018-0509-2
PG 6
ER
PT J
AU Chopra, S
Goel, S
Thakur, B
Bhatia, A
AF Chopra, Sucheta
Goel, Sumit
Thakur, Banita
Bhatia, Alka
TI Do Different Stemness Markers Identify Different Pools of Cancer Stem Cells in Malignancies: A Study on ER+ and ER-Breast Cancer Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Stemness; Breast cancer; Cancer stem cells; Estrogen receptor
ID Stemness; Breast cancer; Cancer stem cells; Estrogen receptor
AB In view of popularity of cancer stem cell (CSC) model all events in evolution of cancer are being explained in that context. Breast cancer is first solid tumor in which CSCs were identified. We aimed to compare stemness profile of two major subtypes [Estrogen receptor positive (ER+) and negative (ER−)] breast cancer using different sets of markers. Expression of CD44/CD24, CK/Vimentin, E-Cadherin/Fibronectin and percentage of side population (SP) was studied in ER+ (T47D) and ER−(MDA-MB-231) cell lines by flow cytometry. Breast CSCs (BCSCs) were sorted using CD44+/CD24−/low expression and SP analysis and cultured. BCSCs were then compared with Non-CSCs (NCSCs) for response to drugs (Paclitaxel and Cisplatin), Ki67 and ER expression. Results showed higher expression of stemness markers (CD44+/CD24−/low, CK+/Vimentin+ and ECadherin−/FibrinectinF+) in MDA-MB-231 cells. Percentage SP representing BCSCs was found to be significantly more in later (3.20 ± 0.002 cf. T47D 1.25%± 0.0007). BCSCs were found to be more resistant to drugs as compared to NCSCs in both cell lines. ER expression was weak in BCSCs sorted from T47D as compared to NCSCs. Ki67 was expressed in both BCSCs and NCSCs. Differences in expression of stemness markers help to explain aggressive behavior, higher recurrence rate and metastatic potential of MDA-MB-231 cells. However, no correlation amongst different markers used suggests that they may be identifying varied populations of cells in tumor hierarchy. A weak ER expression in BCSCs may be strategy used by BCSCs to escape effect of hormone therapy in ER+ breast cancers.
C1 [Chopra, Sucheta] Postgraduate Institute of Medical Education and Research, Department of Experimental Medicine & Biotechnology, 160012 Chandigarh, India.
[Goel, Sumit] Postgraduate Institute of Medical Education and Research, Department of Experimental Medicine & Biotechnology, 160012 Chandigarh, India.
[Thakur, Banita] Postgraduate Institute of Medical Education and Research, Department of Experimental Medicine & Biotechnology, 160012 Chandigarh, India.
[Bhatia, Alka] Postgraduate Institute of Medical Education and Research, Department of Experimental Medicine & Biotechnology, 160012 Chandigarh, India.
RP Bhatia, A (reprint author), Postgraduate Institute of Medical Education and Research, Department of Experimental Medicine & Biotechnology, 160012 Chandigarh, India.
EM alkabhatia@ymail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 371
EP 378
DI 10.1007/s12253-018-0503-8
PG 8
ER
PT J
AU Benesova, L
Halkova, T
Bunganic, B
Belsanova, B
Zavoral, M
Traboulsi, E
Minarik, M
AF Benesova, Lucie
Halkova, Tereza
Bunganic, Bohus
Belsanova, Barbora
Zavoral, Miroslav
Traboulsi, Eva
Minarik, Marek
TI Comparison of Native Aspirates and Cytological Smears Obtained by EUS-Guided Biopsies for Effective DNA/RNA Marker Testing in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EUS-FNA; Pancreatic cancer; KRAS; miR-21
ID EUS-FNA; Pancreatic cancer; KRAS; miR-21
AB We compare two types of pancreatic carcinoma samples obtained by EUS-guided fine needle biopsy (EUS-FNB) in terms of the success rates and clinical validity of analysis of two most commonly investigated DNA/RNA pancreatic cancer markers, KRAS mutations and miR-21 expression. 118 patients with pancreatic ductal adenocarcinoma underwent EUS-FNB. The collected sample was divided, one part was stored in a stabilizing solution as native aspirate (EUS-FNA) and second part was processed into the cytological smear (EUS-FNC). DNA/RNA extraction was followed by analysis of KRAS mutations and miR-21 expression. For both sample types, the yields of DNA/RNA extraction and success rates of KRAS mutation and miRNA expression were evaluated. Finally, the resulting KRAS mutation frequency and miR-21 prognostic role were compared to literature data from tissue resections. The overall amount of isolated DNA/RNA from EUS-FNC was lower compared to the EUS-FNA, average yield 10 ng vs 147 ng for DNA and average yield 164 vs. 642 ng for RNA, but the success rates for KRAS and miR-21 analysis was 100% for both sample types. The KRAS-mutant detection frequency in EUS-FNC was 12% higher than in EUS-FNA (90 vs 78%). The prognostic role of miR-21 was confirmed in EUS-FNC (p = 0.02), but did not reach statistical significance in EUS-FNA (p = 0.06). Although both types of EUS-FNB samples are suitable for DNA/RNA extraction and subsequent DNA mutation and miRNA expression analysis, reliable results with clinical validity were only obtained for EUS-FNC.
C1 [Benesova, Lucie] Genomac Research Institute, Centre for Applied Genomics of Solid Tumors (CEGES), 161 00 Prague, Czech Republic.
[Halkova, Tereza] Genomac Research Institute, Centre for Applied Genomics of Solid Tumors (CEGES), 161 00 Prague, Czech Republic.
[Bunganic, Bohus] Charles University in Prague and General University Hospital in Prague, First Faculty of Medicine, 1st Department of Medicine—Department of Haematology, 169 02 Prague, Czech Republic.
[Belsanova, Barbora] Genomac Research Institute, Centre for Applied Genomics of Solid Tumors (CEGES), 161 00 Prague, Czech Republic.
[Zavoral, Miroslav] Charles University in Prague and General University Hospital in Prague, First Faculty of Medicine, 1st Department of Medicine—Department of Haematology, 169 02 Prague, Czech Republic.
[Traboulsi, Eva] Military University Hospital, Pathology department, 169 02 Prague, Czech Republic.
[Minarik, Marek] Genomac Research Institute, Centre for Applied Genomics of Solid Tumors (CEGES), 161 00 Prague, Czech Republic.
RP Minarik, M (reprint author), Genomac Research Institute, Centre for Applied Genomics of Solid Tumors (CEGES), 161 00 Prague, Czech Republic.
EM mminarik@email.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 379
EP 385
DI 10.1007/s12253-018-0490-9
PG 7
ER
PT J
AU Li, K
Liu, Y
Xu, Sh
Wang, J
AF Li, Ke
Liu, Ying
Xu, Shuning
Wang, Jufeng
TI PPM1D Functions as Oncogene and is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Protein phosphatase Mg2+/Mn2+ dependent1D; Esophageal squamous cell carcinoma; Tumor metastasis; Prognosis
ID Protein phosphatase Mg2+/Mn2+ dependent1D; Esophageal squamous cell carcinoma; Tumor metastasis; Prognosis
AB Mounting evidence has demonstrated that PPM1D participates in the development and progression of a wide variety of tumors. However, its precise roles in esophageal squamous cell carcinoma (ESCC) remain under investigation. Here, UALCAN, an interactive web-portal to perform the expression analyses of PPM1D using TCGA gene expression data, and PPM1D high expression was exhibited in primary esophageal cancer. Further investigation revealed that PPM1D expression was obviously higher in ESCC tissues than in normal tissues (P < 0.01), which was consistent with the results from real-time qPCR and Western blotting in ESCC tissues and paired normal esophageal tissues. Besides, PPM1D expression was closely correlated with TNM staging, tumor differentiation and lymph node metastasis (P < 0.01), but not related to the patients’ gender and age (P > 0.05). Notably, PPM1D expression in metastatic ESCC patients was markedly higher than that in non-metastatic ESCC patients (P < 0.01), and the ESCC patients with high PPM1D expression predicted poor prognosis. Multivariate assay demonstrated that PPM1D and lymph node metastasis were considered as independent prognostic factors for the ESCC patients. These findings suggest PPM1D plays a pivotal important role in onset and progression of ESCC, and may be a new biomarker for metastasis and prognosis of the ESCC patients.
C1 [Li, Ke] Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 127th Dongming Rd, 450008 Zhengzhou, Henan Province, China.
[Liu, Ying] Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 127th Dongming Rd, 450008 Zhengzhou, Henan Province, China.
[Xu, Shuning] Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 127th Dongming Rd, 450008 Zhengzhou, Henan Province, China.
[Wang, Jufeng] Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 127th Dongming Rd, 450008 Zhengzhou, Henan Province, China.
RP Wang, J (reprint author), Affiliated Cancer Hospital of Zhengzhou University, Department of Medical Oncology, 450008 Zhengzhou, China.
EM wangjf1101@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 387
EP 395
DI 10.1007/s12253-018-0518-1
PG 9
ER
PT J
AU Imredi, E
Liszkay, G
Kenessey, I
Plotar, V
Godeny, M
Toth, B
Fedorcsak, I
Timar, J
AF Imredi, Eleonora
Liszkay, Gabriella
Kenessey, Istvan
Plotar, Vanda
Godeny, Maria
Toth, Bela
Fedorcsak, Imre
Timar, Jozsef
TI Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AQP1 protein; Cutaneous melanoma; Melanoma brain metastases; Metastatic melanoma
ID AQP1 protein; Cutaneous melanoma; Melanoma brain metastases; Metastatic melanoma
AB Brain metastasis is a frequent complication of the progression of malignant melanoma. In a previous study aquaporin 1 (AQP1) protein expression was found to be associated with increased mortality and decreased progression free survival in cutaneous melanoma. To explore further the potential of this marker we studied the AQP1 protein expression in 67 metastatic melanoma patients using immunohistochemistry. Primary tumor samples were acquired from patients with brain (BR) (n = 44) and extracranial (EC) (n = 23) metastases, while brain metastatic samples were collected during neurosurgical resection (n = 5). Patients with brain metastases had shorter overall survival (p = 0.02) and significantly higher AQP1 expression in the primary tumors (median H-score = 250 vs. 140, p = 0.044) as compared to patients of the EC metastasis group. AQP1 expression was found to be significantly lower in the brain metastases compared to the corresponding primary tumors (median H-score = 35 vs. 300 p = 0.01). However, in brain metastases AQP1 expression was heterogenous, AQP1 protein was more abundant in the melanoma cells far away from the capillaries as compared to tumor cells adjacent to vessels indicating a hypoxia-driven expression of AQP1. We suggest that AQP1 expression could well be a prognostic marker of brain metastatic potential of human cutaneous melanoma.
C1 [Imredi, Eleonora] Semmelweis University, 2nd Department of Pathology, Ulloi Str 93, H-1091 Budapest, Hungary.
[Liszkay, Gabriella] National Institute of OncologyBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, Ulloi Str 93, H-1091 Budapest, Hungary.
[Plotar, Vanda] National Institute of OncologyBudapest, Hungary.
[Godeny, Maria] National Institute of OncologyBudapest, Hungary.
[Toth, Bela] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Fedorcsak, Imre] National Institute of Clinical NeurosciencesBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi Str 93, H-1091 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM jtimar@gmail.com
CR Franceschini D, Franzese C, Navarria P, Ascolese AM, De Rose F, Del Vecchio M et al, 2016, Radiotherapy and immunotherapy: can this combination change the prognosis of patients with melanoma brain metastases? Cancer Treat Rev 50:1–8
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 405
EP 410
DI 10.1007/s12253-018-0513-6
PG 6
ER
PT J
AU Ahmed, AHM
Ali, HM
Abbas, HH
Elatrash, AG
Foda, AMA
AF Ahmed, A H Mohamed
Ali, Hassan Mohamed
Abbas, Hafez Hashem
Elatrash, Ali Gamal
Foda, AlRahman Mohammad Abd
TI Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TOMM34; Urothelial; Mitochondrial; Markers
ID TOMM34; Urothelial; Mitochondrial; Markers
AB The substantial difference between normal cells and cancer cells in terms of their energy metabolism in mitochondria provides an interesting basis for the development of novel therapeutic agents targeting energy machinery of tumour cells. TOMM34 is one of the Tom (translocase of the outer membrane of mitochondria) family that was found to be overexpressed in colorectal, hepatocellular, lung and early invasive breast carcinomas. The expression profile of mitochondrial translocases in bladder cancer compared to normal urinary bladder tissues has not been investigated yet. Therefore, the aim of the current study is to investigate the expression pattern of TOMM34 in bladder cancer tissues and explore its correlation with the clinicopathological parameters of those cases. Sixty patients who underwent either transurethral resection or radical cystectomy for bladder cancer were included in this study with revision of all their clinicopathological data and tumor slides. Ten histologically normal urothelial biopsies were also included. Immunohistochemical staining for TOMM34 was done and semi-quantitatively scored using the modified H-score. All relations were analysed using established statistical methodologies. TOMM34 overexpression was significantly associated with high tumour stage, muscle invasion and high grade. Significant positive association was observed between TOMM34 expression and poor outcome in terms of shorter disease-specific survival. This study suggests TOMM34 as a biomarker of progression and poor prognosis in urothelial cell carcinoma patients. Furthermore, we suggest a role played by mitochondrial machinery in urothelial cell carcinoma progression, which is a potential target for the newly-discovered vaccine therapy for urothelial cell carcinoma.
C1 [Ahmed, A H Mohamed] Suez Canal University, Faculty of Medicine, Department of PathologyIsmailia, Egypt.
[Ali, Hassan Mohamed] Suez Canal University, Faculty of Medicine, Department of UrologyIsmailia, Egypt.
[Abbas, Hafez Hashem] Suez Canal University, Faculty of Medicine, Department of UrologyIsmailia, Egypt.
[Elatrash, Ali Gamal] Suez Canal University, Faculty of Medicine, Department of UrologyIsmailia, Egypt.
[Foda, AlRahman Mohammad Abd] Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
RP Foda, AMA (reprint author), Mansoura University, Faculty of Medicine, Department of Pathology, 35516 Mansoura, Egypt.
EM abdofoda@mans.edu.eg
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 411
EP 418
DI 10.1007/s12253-018-0524-3
PG 8
ER
PT J
AU Pal, I
Illes,
Varoczy, L
AF Pal, Ildiko
Illes, Arpad
Varoczy, Laszlo
TI Multiple Myeloma of the Young – a Single Center Experience Highlights Future Directions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiple myeloma; Young; 40 years; Progression-free survival; Overall survival
ID Multiple myeloma; Young; 40 years; Progression-free survival; Overall survival
AB Multiple myeloma is quite uncommon in the young population. We performed a retrospective review in our database from 2006 to 2015 to examine the clinical features, outcomes and survival of multiple myeloma patients ≤40 years old. Among 312 newly diagnosed patients we found sixteen (5.1%) who were 40 years old or younger. Their characteristics including M-protein type, genetical alterations, clinical symptoms and disease stage were as various as those in the older population. All but two young patients underwent autologous stem cell transplantation after the induction treatment. Their response to treatment did not differ markedly from the older patients. We also compared the survival data of patients ≤40 years and > 40 years old. The 5-year progression-free survival were 48% and 35%, the 5-year overall survival were 83% and 53% respectively, the latter showing a significant advantage for the younger population. 70% of the young patients received maintenance or consolidation therapy after the initial treatment. Although several effective new therapies have been introduced recently, there is still an unmet need for curative treatment options for young and fit multiple myeloma patients.
C1 [Pal, Ildiko] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Varoczy, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, H-4032 Debrecen, Hungary.
EM laszlo.varoczy@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 419
EP 424
DI 10.1007/s12253-018-0526-1
PG 6
ER
PT J
AU An, N
Cheng, D
AF An, Ning
Cheng, Donghui
TI The Long Noncoding RNA HOST2 Promotes Gemcitabine Resistance in Human Pancreatic Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic neoplasms; LncRNA; HOST2; Gemcitabine
ID Pancreatic neoplasms; LncRNA; HOST2; Gemcitabine
AB Our study was aimed to identify the fundamental role of lncRNA HOST2 in gemcitabine resistance regulation in human pancreatic cancer cells. The levels of HOST2 in pancreatic cancer cell lines were measured by quantitative real-time PCR (qRT-PCR). Due to high expression and strong gemcitabine resistance, Hs766T and AsPC-1 cell lines were selected to be knockdown the expression of HOST2 by transfection sh-HOST2. After manipulation of HOST2, the cell proliferation induced by gemcitabine was examined by CCK-8 assay. Next, colony formation ability of Hs766Tand AsPC-1 cell lines was determined by clone-forming assay. At last, the relationship between HOST2 and cell apoptosis in Hs766T and AsPC-1 cell lines was evaluated by flow cytometry. QRT-PCR revealed that HOST2 was overexpressed in six pancreas neoplasm cell lines compared with normal cell lines HPDE6-C7. HOST2 expression levels in group resistant to gemcitabine were higher than the group sensitive to gemcitabine. Additionally, CCK-8 assay verified that cell proliferation was inhibited by sh-HOST2 with or without gemcitabine treatment. Furthermore, clone-forming assay revealed that colony formation ability was weakened by downregulated HOST2 with or without gemcitabine treatment. Flow cytometry revealed that cell apoptosis induced by gemcitabine was promoted by sh-HOST2. In conclusion, down-regulated HOST2 inhibited proliferation and promoted apoptosis of pancreas cancer cells with or without gemcitabine treatment. Thus, HOST2 is a potential therapeutic target for gemcitabine chemoresistance in pancreatic neoplasms.
C1 [An, Ning] Sichuan Medical Academy & Sichuan People′s Hospital, Department of Hepatobiliary Surgery, No 32 Western Third Section of First Ring Road, 610072 Chengdu, Sichuan, China.
[Cheng, Donghui] Sichuan Medical Academy & Sichuan People′s Hospital, Department of Hepatobiliary Surgery, No 32 Western Third Section of First Ring Road, 610072 Chengdu, Sichuan, China.
RP Cheng, D (reprint author), Sichuan Medical Academy & Sichuan People′s Hospital, Department of Hepatobiliary Surgery, 610072 Chengdu, China.
EM chengyongqin111111@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 425
EP 431
DI 10.1007/s12253-018-0486-5
PG 7
ER
PT J
AU de Souza, GM
de Jesus, FS
Santos, ME
Gomes, SBE
Filho, dPSA
Santos, MSE
da Silveira, HL
Santos, HSS
de Paula, MBA
Farias, CL
Guimaraes, LSA
AF de Souza, Goncalves Marcela
de Jesus, Ferreira Sabrina
Santos, Mangabeira Eloa
Gomes, Stenio Batista Emisael
Filho, de Paulo Santiago Arlen
Santos, Macedo Sobrinho Eliane
da Silveira, Henrique Luiz
Santos, Henrique Sousa Sergio
de Paula, Mauricio Batista Alfredo
Farias, Conceicao Lucyana
Guimaraes, Luiz Sena Andre
TI Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Radiotherapy; Warburg effect; OSCC
ID Radiotherapy; Warburg effect; OSCC
AB Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.
C1 [de Souza, Goncalves Marcela] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[de Jesus, Ferreira Sabrina] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Santos, Mangabeira Eloa] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Gomes, Stenio Batista Emisael] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Filho, de Paulo Santiago Arlen] Hospital Dilson GodinhoMontes Claros, Minas Gerais, Brazil.
[Santos, Macedo Sobrinho Eliane] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[da Silveira, Henrique Luiz] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Santos, Henrique Sousa Sergio] Universidade Federal de Minas Gerais (UFMG), Food Engineering College, Institute of Agricultural SciencesMontes Claros, Minas Gerais, Brazil.
[de Paula, Mauricio Batista Alfredo] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Farias, Conceicao Lucyana] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
[Guimaraes, Luiz Sena Andre] Universidade Estadual de Montes Claros, Department of DentistryMontes Claros, Minas Gerais, Brazil.
RP Guimaraes, LSA (reprint author), Universidade Estadual de Montes Claros, Department of Dentistry, Montes Claros, Brazil.
EM andreluizguimaraes@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 433
EP 442
DI 10.1007/s12253-018-0517-2
PG 10
ER
PT J
AU Li, Y
Bai, W
Zhang, L
AF Li, Yuanhang
Bai, Weijun
Zhang, Linlin
TI The Overexpression of CD80 and ISG15 Are Associated with the Progression and Metastasis of Breast Cancer by a Meta-Analysis Integrating Three Microarray Datasets
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Microarray data; Meta-analysis; Breast cancer; Metastasis
ID Microarray data; Meta-analysis; Breast cancer; Metastasis
AB Breast cancer is a common cancer and could result in a substantial mortality. The study aimed to screen gene signatures associated with the development and metastasis of breast cancer and explore their regulation mechanisms. Three datasets of GSE10797, GSE8977 and GSE3744 were downloaded from GEO (Gene Expression Omnibus) database, containing 55 breast cancer samples and 27 normal samples. After data preprocessing using limma software and RMA (robust multiarray average) algorithm, DEGs (differentially expressed genes) between breast tumor and normal tissues in three individual experiments were identified using MADAM package. Function and pathway enrichment analyses were performed for the DEGs. Transcription factors and TAGs (tumor associated genes) among the DEGs were recognized and the PPI (protein-protein-interaction) network for the DEGs was constructed using Cytoscape software. The mRNA expression was analyzed via real-time quantitative PCR and protein expression was measured by western blotting. Totally, 100 DEGs were identified, including 33 up-regulated genes and 67 down-regulated genes. Among them, up-regulated DEGs such as CD80 was enriched in toll-like receptor (TLR) interaction pathway and the TAG, ISG15 was related to RIG-I-like receptor signaling pathway, while CXCL10 was involved in both of the two pathways. Whereas, the down-regulated DEG, CXCL12 was significantly associated with axon guidance pathway. Additionally, these DEGs were also pivotal nodes in the PPI network with high degrees. Besides, CXCL10 and CD80 were both interacted with IFNG. The mRNA expression of ISG15 was obviously enhanced in human breast cancer cells MCF-7, while no significant difference of CXCL10 mRNA level was found between MCF10A and MCF-7 cells. Moreover, the proteins expression levels of CD80 and ISG15 were significantly increased in MCF-7, MDA-MB-468 and MDA-MB-231 breast cancer cells than in normal MCF10A cells. CD80 might be responsible for the breast cancer’s progression and metastasis via regulating innate immune system. In addition, ISG15 is identified as a crucial gene signature associated with breast cancer development and metastasis via RIGI-like receptor signaling pathway.
C1 [Li, Yuanhang] Cancer Hospital of China Medical University, Medical Department, No. 44 Xiaoheyan Road, Dadong District, 110042 Shenyang, Liaoning Province, China.
[Bai, Weijun] Cancer Hospital of China Medical University, Medical Department, No. 44 Xiaoheyan Road, Dadong District, 110042 Shenyang, Liaoning Province, China.
[Zhang, Linlin] Cancer Hospital of China Medical University, Medical Department, No. 44 Xiaoheyan Road, Dadong District, 110042 Shenyang, Liaoning Province, China.
RP Li, Y (reprint author), Cancer Hospital of China Medical University, Medical Department, 110042 Shenyang, China.
EM yuanhangli619@hotmail.com
CR Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF, 2003, Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci 100:3983–3988
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Cui X-F, Imaizumi T, Yoshida H, Borden EC, Satoh K, 2004, Retinoic acid-inducible gene-I is induced by interferon-γ and regulates the expression of interferon-γ stimulated gene 15 in MCF-7 cells. Biochem Cell Biol 82:401–405
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 443
EP 452
DI 10.1007/s12253-018-0478-5
PG 10
ER
PT J
AU Lee, S
Ahn, YM
Kim, JY
Cho, YE
Park, JH
AF Lee, Sun
Ahn, Yong-Min
Kim, Jee-Youn
Cho, Young-Eun
Park, Jae-Hoon
TI Downregulation of NOP53 Ribosome Biogenesis Factor Leads to Abnormal Nuclear Division and Chromosomal Instability in Human Cervical Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NOP53; Mitosis; Abnormal nucleus; Chromosomal instability
ID NOP53; Mitosis; Abnormal nucleus; Chromosomal instability
AB NOP53 ribosome biogenesis factor (NOP53) is a nucleolar protein involved in oncogenesis/tumor suppression, cell cycle regulation, and cell death. Here, we investigated the role of NOP53 in the maintenance of normal nuclear shape and chromosomal stability. Depletion of NOP53 by shRNA caused abnormal nuclear morphology, including large nucleus, irregular nucleus, and multinucleated cells, and chromosomal instability resulting in micronucleus or nuclear bud formation. The abnormal nuclear shape and chromosomal instability were restored by re-expression of NOP53. We further showed that NOP53 was involved in chromosome congression in metaphase. Downregulation of NOP53 induced aberrant chromosome congression and spindle checkpoint activation, resulting in delayed mitosis and mitotic arrest. Thus, our findings demonstrated that the nucleolar protein NOP53 participated in mitotic progression and that dysregulated NOP53 expression caused chromosomal instability in cancer cells.
C1 [Lee, Sun] Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
[Ahn, Yong-Min] Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
[Kim, Jee-Youn] Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
[Cho, Young-Eun] Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
[Park, Jae-Hoon] Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
RP Park, JH (reprint author), Kyung Hee University, College of Medicine, Department of Pathology, 02453 Seoul, South Korea.
EM jhpark@khu.ac.kr
CR Boulon S,Westman BJ, Hutten S, Boisvert FM, Lamond AI, 2010, The nucleolus under stress. Mol Cell 40:216–227
Amin MA, Matsunaga S, Uchiyama S, Fukui K, 2008, Depletion of nucleophosmin leads to distortion of nucleolar and nuclear structures in HeLa cells. Biochem J 415:345–351
Amin MA, Matsunaga S, Ma N, Takata H, Yokoyama M, Uchiyama S, Fukui K, 2007, Fibrillarin, a nucleolar protein, is required for normal nuclear morphology and cellular growth in HeLa cells. Biochem Biophys Res Commun 360:320–326
Kalt I, Levy A, Borodianskiy-Shteinberg T, Sarid R, 2012, Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences. PLoS One 7:e30825
Kim JY, Seok KO, Kim YJ, Bae WK, Lee S, Park JH, 2011, Involvement of GLTSCR2 in the DNA damage response. Am J Pathol 179:1257–1264
Lee S, Kim JY, Kim YJ, Seok KO, Kim JH, Chang YJ, Kang HY, Park JH, 2012, Nucleolar protein GLTSCR2 stabilizes p53 in response to ribosomal stresses. Cell Death Differ 19:1613–1622
Yim JH, Kim YJ, Ko JH, Cho YE, Kim SM, Kim JY, Lee S, Park JH, 2007, The putative tumor suppressor gene GLTSCR2 induces PTEN-modulated cell death. Cell Death Differ 14:1872–1879
Shibamoto Y, Streffer C, Fuhrmann C, Budach V, 1991, Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay. Radiat Res 128:293–300
Kim JY, Cho YE, Park JH, 2015, The nucleolar protein GLTSCR2 is an upstream negative regulator of the oncogenic nucleophosmin- MYC axis. Am J Pathol 185:2061–2068
Ugrinova I, Monier K, Ivaldi C, Thiry M, Storck S, Mongelard F, Bouvet P, 2007, Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol Biol 8:66
Ma N, Matsunaga S, Takata H, Ono-Maniwa R, Uchiyama S, Fukui K, 2007, Nucleolin functions in nucleolus formation and chromosome congression. J Cell Sci 120:2091–2105
Tsai RY, Pederson T, 2014, Connecting the nucleolus to the cell cycle and human disease. FASEB J 28:3290–3296
Takada H, Kurisaki A, 2015, Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging. Cell Mol Life Sci 72:4015–4025
Amin MA, Matsunaga S, Uchiyama S, Fukui K, 2008, Nucleophosmin is required for chromosome congression, proper mitotic spindle formation, and kinetochore-microtubule attachment in HeLa cells. FEBS Lett 582:3839–3844
Maraldi NM, Lattanzi G, Capanni C, Columbaro M, Merlini L, Mattioli E, Sabatelli P, Squarzoni S, Manzoli FA, 2006, Nuclear envelope proteins and chromatin arrangement: a pathogenic mechanism for laminopathies. Eur J Histochem 50:1–8
Vogt E, Kirsch-Volders M, Parry J, Eichenlaub-Ritter U, 2008, Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error. Mutat Res 651:14–29
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 453
EP 459
DI 10.1007/s12253-018-0531-4
PG 7
ER
PT J
AU Farsani, AM
Kamel, M
Mehrpouri, M
Heris, ShR
Hamidpour, M
Salari, S
Mohamadi, HM
AF Farsani, Allahbakhshian Mehdi
Kamel, Masomeh
Mehrpouri, Mahdieh
Heris, Shiri Reza
Hamidpour, Mohsen
Salari, Sina
Mohamadi, Hosien Mohamad
TI The Expression of Interferon Gamma (IFN-γ) and Interleukin 6 (IL6) in Patients with Acute Lymphoblastic Leukemia (ALL)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALL; IFN-γ; IL-6
ID ALL; IFN-γ; IL-6
AB Interferon gamma (IFN-γ) and interleukin 6 (IL-6) are including the most important cytokines which have been associated with the biological behavioral and immune responses in malignancies. Based on the critical roles which these two cytokines play against tumor cells, the present study was aimed to investigate the genes expression level of IL6 and IFN-γ in patients with Acute Lymphoblastic Leukemia and compare with normal controls. Fifty-two patients with ALL and 13 healthy volunteer were under studied. The peripheral blood mononuclear cells of all patients and normal controls were separated by ficoll. The expression of interferon gamma and interleukin 6 genes were determined by RQ-PCR. Finally all data were analyzes using T student, one way ANOVA and Mann-Whitney tests were use to analyze all samples data. Our finding showed that the level of IFN-γ gene expression was significant decreased in patients with All as compared with healthy controls (83 change fold, p < 0.0001). The level of IL-6 Gene expression was not changeable in B-ALL patients as compared with healthy control (p = 0.4), but in T-ALL patients, was significantly reduced (p < 0.01). The results of present study indicated that IFN-γ gene expression reduced in ALL patients. It provides a valuable insight that immune system may disrupted in patients with ALL, which cause tumor cells escape from immune surveillance.
C1 [Farsani, Allahbakhshian Mehdi] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
[Kamel, Masomeh] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
[Mehrpouri, Mahdieh] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
[Heris, Shiri Reza] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
[Hamidpour, Mohsen] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
[Salari, Sina] Shahid Beheshti University of Medical Sciences, Taleghani General Hospital, Department of Internal MedicineTehran, Iran.
[Mohamadi, Hosien Mohamad] Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood BankingTehran, Iran.
RP Hamidpour, M (reprint author), Shahid Beheshti University of Medical Sciences, School of Allied Medical Sciences, Department of Hematology and Blood Banking, Tehran, Iran.
EM mohsenhp@sbmu.ac.ir
CR Harrison CJ, 2013, Targeting signaling pathways in acute lymphoblastic leukemia: new insights. American Society of Hematology, Education Program 2013(1):118–125
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Heikkila K, Ebrahim S, Lawlor DA, 2008, Systematic review of the association between circulating interleukin-6, IL-6, and cancer. Eur J Cancer 44:937–945
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Grander D, Heyman M, Brondum-Nielsen K, Liu Y, Lundgren E, Soderhall S, Einhorn S, 1992, Interferon system in primary acute lymphocytic leukemia cells with or without deletions of the − 0.5). The mean survival time was 72.7 ± 7.82 months. Survival rates for 1, 3 and 5 years were 93%, 65% and 45%, respectively. The mean LODDS value was −1.0466 ± 0.51. LODDS subgroups show strong correlation with Overall Survival (OS). The mean survival were 114.8, 81.8, 56.6 and 25.6 months in LODDS subgroups 1, 2, 3 and 4, respectively (Log-rank; p = 0.002), in addition LOODS values shows correlation with perineural invasion and micro vascular invasion (p = 0.015 and p = 0.001 respectively). Findings in our patient group support the hypothesis that LODDS subgroups correlate with OS, and that value of LODDS has considerable role in prediction of OS as well.
C1 [Agalar, Cihan] Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, Balcova, Inciralti, 35340 Izmir, Turkey.
[Aysal, Anil] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Unek, Tarkan] Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, Balcova, Inciralti, 35340 Izmir, Turkey.
[Egeli, Tufan] Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, Balcova, Inciralti, 35340 Izmir, Turkey.
[Ozbilgin, Mucahit] Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, Balcova, Inciralti, 35340 Izmir, Turkey.
[Akturk, Nesrin] Dokuz Eylul University, Faculty of Medicine, Department of Radiation OncologyIzmir, Turkey.
[Semiz, Salih Huseyin] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Unek, Tugba] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Akarsu, Mesut] Dokuz Eylul University School of Medicine, The Department of GastroenterologyIzmir, Turkey.
[Soyturk, Mujde] Dokuz Eylul University School of Medicine, The Department of GastroenterologyIzmir, Turkey.
[Ellidokuz, Hulya] Dokuz Eylul University, Institute of OncologyIzmir, Turkey.
[Sagol, Ozgul] Dokuz Eylul University, Faculty of Medicine, Department of PathologyIzmir, Turkey.
[Astarcioglu, Ibrahim] Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, Balcova, Inciralti, 35340 Izmir, Turkey.
RP Agalar, C (reprint author), Dokuz Eylul University, Faculty of Medicine, Department of General Surgery, 35340 Izmir, Turkey.
EM cihan.agalar@deu.edu.tr
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 467
EP 473
DI 10.1007/s12253-019-00584-6
PG 7
ER
PT J
AU Fang, J
Chen, W
Meng, XL
AF Fang, Jun
Chen, Wei
Meng, Xiang-Ling
TI LncRNA CASC9 Suppressed the Apoptosis of Gastric Cancer Cells through Regulating BMI1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lncRNA CASC9; BMI1; Gastric cancer; Ubiquitination; Degradation
ID lncRNA CASC9; BMI1; Gastric cancer; Ubiquitination; Degradation
AB Long noncoding RNAs (lncRNAs) play important roles in regulating the apoptosis of gastric cancer (GC) cells. This study aims to investigate the underlying mechanism of lncRNA CASC9 in regulating the apoptosis of GC cells. The expressions of lncRNA and protein in GC tissues and cell lines were detected by qRT-PCR and western blot. GC cell apoptosis was detected by flow cytometry analysis. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to verify the interaction between CASC9 and BMI1. LncRNA CASC9 was upregulated in GC tissue and GC cells, and high CASC9 expression was positively correlated with TNM stage and lymph node metastasis. Silencing CASC9 promoted the apoptosis of GC cells. LncRNA CASC9 could interact with BMI1 and positively regulate BMI1 expression. Silencing CASC9 promoted the ubiquitination of BMI1. In addition, lncRNA CASC9 regulated the apoptosis of GC cells through BMI1. Furthermore, interfering CASC9 inhibited the tumor growth of GC. LncRNA CASC9 could interact with BMI1 to regulate the degradation of BMI1, thus to affect the apoptosis of GC cells and suppressed tumor growth.
C1 [Fang, Jun] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 218 Jixi Rd., 230022 Hefei, Anhui, China.
[Chen, Wei] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 218 Jixi Rd., 230022 Hefei, Anhui, China.
[Meng, Xiang-Ling] The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 218 Jixi Rd., 230022 Hefei, Anhui, China.
RP Fang, J (reprint author), The First Affiliated Hospital of Anhui Medical University, Department of General Surgery, 230022 Hefei, China.
EM 102473526@qq.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 475
EP 482
DI 10.1007/s12253-019-00703-3
PG 8
ER
PT J
AU Aguin, N
Rodriguez-Alonso, A
Lopez-Trigo, N
Castuera, P
Luis, RJ
Caeiro, B
AF Aguin, Nerea
Rodriguez-Alonso, Andres
Lopez-Trigo, Nuria
Castuera, I. Perez
Luis, Rodriguez Javier
Caeiro, Blazquez
TI Association Between the Interleukin-17 Gene Polymorphism -197G>A and the Risk of Prostate Cancer in a Galician Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Interleukin-17A (IL-17A); SNP; Prostate cancer (PCa); Inflammation
ID Interleukin-17A (IL-17A); SNP; Prostate cancer (PCa); Inflammation
AB A case-control study was carried out in which the role of the Single Nucleotide Polymorphism rs2275913 in the pathogenesis of prostate cancer was analysed for the first time. This polymorphism is located in −197 position of IL-17A gene and implies a A>G change. The sample consists of 433 Galician men, 241 of whom are prostate cancer patients and 192 are healthy men with no tumours. Besides the influence of this marker, directly involved in the inflammatory process, other variables that were described as prostate cancer risk factors were also studied: age, smoking and Body Mass Index (BMI). By the analysis of Odds Ratio (OR) (CI 95%) a protective effect of heterozygous genotype AG was observed in comparison with homozygous genotypes AA and GG. As regards other risk factors, a significant increased risk was observed in smokers homozygous between 10 and 32 packyears (p = 0.032). Age and BMI show interesting patterns, but not significant ones. This study shows a possible link between the rs2275913 and the onset of PCa which could be influenced by age, BMI and above all, smoking.
C1 [Aguin, Nerea] Universidade de Santiago de Compostela, Facultade de Bioloxia, Area de Antropoloxia Fisica, 15702 Santiago de Compostela, Galicia, Spain.
[Rodriguez-Alonso, Andres] Hospital Arquitecto Marcide, Servicio de Uroloxia, 15405 Ferrol, Galicia, Spain.
[Lopez-Trigo, Nuria] Universidade de Santiago de Compostela, Facultade de Bioloxia, Area de Antropoloxia Fisica, 15702 Santiago de Compostela, Galicia, Spain.
[Castuera, I. Perez] Universidade de Santiago de Compostela, Facultade de Enfermeria, 15702 Santiago de Compostela, Galicia, Spain.
[Luis, Rodriguez Javier] Universidade de Santiago de Compostela, Facultade de Bioloxia, Area de Antropoloxia Fisica, 15702 Santiago de Compostela, Galicia, Spain.
[Caeiro, Blazquez] Universidade de Santiago de Compostela, Facultade de Bioloxia, Area de Antropoloxia Fisica, 15702 Santiago de Compostela, Galicia, Spain.
RP Aguin, N (reprint author), Universidade de Santiago de Compostela, Facultade de Bioloxia, Area de Antropoloxia Fisica, 15702 Santiago de Compostela, Spain.
EM Nerea.aguin@gmail.com
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Cong J, Liu R,Wang X, Sheng L, Jiang H,WangW, ZhangY, Yang S, Li C, 2015, Association between interleukin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population. Int J Clin Exp Pathol 8:9567–9573
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 483
EP 489
DI 10.1007/s12253-018-0537-y
PG 7
ER
PT J
AU Liu, Y
Yang, B
Zhang, X
Huang, Q
Liu, H
AF Liu, Yanhui
Yang, Bo
Zhang, Xiaoyan
Huang, Quanfei
Liu, Hailiang
TI The Gene Mutation Spectrum of Breast Cancer Analyzed by Semiconductor Sequencing Platform
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Semiconductor sequencing platform (SSP); Breast cancer; Mutate spectrum; Genetic screening
ID Semiconductor sequencing platform (SSP); Breast cancer; Mutate spectrum; Genetic screening
AB To use the semiconductor sequencing platform (SSP) to analyze the gene mutate spectrum of breast cancer patients. We recruited 46 breast cancer patients, and detected the ER/PR/HER2 expression level of the tumor tissue by immunohistochemistry. In addition, combined with SSP technology, we detected 207 hot mutation regions of 50 breast cancer related genes with multiple polymerase chain reaction (PCR) technology. There were 8 cases of grade I, 18 cases of grade II, 20 cases of grade III in 46 breast cancer patients according to histological grade and 12 cases of ER/PR + HER2 +, 18 cases of ER/PR + HER2−, 13 cases of ER/PR - HER2 +, 20 cases of ER/PR − HER2− according to ER/PR/HER2 status classification. Moreover, we found that there were 33 gene locus mutations of 8 genes including AKT1, APC, BRAF, CDKN2A, KRAS, PTEN, PIK3CA and TP53, but difference was not statistically significant (P > 0.05) when compared these gene mutations (except for PIK3CA) in each groups according to the histological classification of breast cancer and the ER/PR/HER2 classification. PIK3CA mutation rate of grade I was obviously higher than that of grade II ~ III histological grading in breast cancer patients (P < 0.05). Based on our results, we drew a conclusion that the occurrence and development of breast cancer was a process involved multiple genes. Here, we found that PIK3CA played a role in the development of the early stage of breast cancer, which could provide clinical basis for treatment of breast cancer. Moreover, SSP technology could be an effective and sensitive method for detection of gene mutation spectrum in breast cancer.
C1 [Liu, Yanhui] Dongguan Maternal and Child Health Hospital, Dongguan Institute of Reproductive and Genetic Research, 523000 Dongguan, Guangdong, China.
[Yang, Bo] Dongguan Maternal and Child Health Hospital, Dongguan Institute of Reproductive and Genetic Research, 523000 Dongguan, Guangdong, China.
[Zhang, Xiaoyan] Dongguan Maternal and Child Health Hospital, Dongguan Institute of Reproductive and Genetic Research, 523000 Dongguan, Guangdong, China.
[Huang, Quanfei] CapitalBio Technology Inc., 101111 Beijing, China.
[Liu, Hailiang] CapitalBio Technology Inc., 101111 Beijing, China.
RP Liu, Y (reprint author), Dongguan Maternal and Child Health Hospital, Dongguan Institute of Reproductive and Genetic Research, 523000 Dongguan, China.
EM liuliang71215@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 491
EP 497
DI 10.1007/s12253-018-0522-5
PG 7
ER
PT J
AU Wang, Xe
Wang, Yh
Zhou, Q
Peng, M
Zhang, J
Chen, M
Ma, Lj
Xie, GM
AF Wang, Xi-en
Wang, You-hui
Zhou, Qiang
Peng, Min
Zhang, Jing
Chen, Mi
Ma, Li-juan
Xie, Guo-Ming
TI Immunomodulatory Effect of Lentinan on Aberrant T Subsets and Cytokines Profile in Non-small Cell Lung Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Chemo-immunotherapy; Lentinan; T cell subsets
ID Non-small cell lung cancer; Chemo-immunotherapy; Lentinan; T cell subsets
AB As a purified active component from traditional Chinese medicine, lentinan administration can be applied as beneficial chemoimmunotherapy for anti-tumor. In this study, the immunomodulatory effects of lentinan on aberrant T subsets and cytokines profile were evaluated for non-small cell lung cancer (NSCLC). Of all NSCLC patients treated with NP chemotherapeutic protocol (combination of vinorelbin and cisplatin), 73 cases were recruited in this retrospective cohort trial study, of which 38 cases received additional lentinan. The changes of aberrant T subsets and cytokines profile were compared between two groups (chemotherapy in combination with lentinan vs. conserved single chemotherapy) by flow cytometry and molecular biology. Higher subset ratio of CD3+CD8+ cytotoxic T cells was confirmed in the peripheral blood of NSCLC patients. Chemoimmunotherapy of lentinan resulted in a significant increase of CD3 + CD56+ NKT cells (15.7 ± 3.1%), compared with 8.6 ± 1.4% of NKT cells in single chemotherapy group, and up-regulated CD3+CD8+ and CD3+CD4+ subsets as well, but caused the decrease of CD4+CD25+ Tregs induction, accompanied by significant alleviation of IL-10 and TGF-β1, and elevation of IFN-γ, TNF-α, and IL-12 (P < 0.05). It could be confirmed that lentinan could not only enhance the cellular immunity and promote the beneficial of anti-tumor by associated immunotherapy, but also had the ability to inhibit the expansion of immune suppressive Tregs in the NSCLC patients, in whom there was a raised Tregs induction compared to health control. Lentinan-based chemoimmunotherapy is a promising strategy for anti-tumor via enhancing the proliferation of cytotoxic T cells, followed by the elevation of inflammatory chemokines/cytokines. Meanwhile, the percentage of CD4+ CD25+ Tregs is down-regulated, leading to a shift in the inflammatory status from Th2 to Th1 in NSCLC patients treated with lentinan.
C1 [Wang, Xi-en] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Wang, You-hui] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Zhou, Qiang] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Peng, Min] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Zhang, Jing] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Chen, Mi] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Ma, Li-juan] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
[Xie, Guo-Ming] Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, Zhejiang, China.
RP Wang, Xe (reprint author), Ningbo Yinzhou People Hospital, Department of Integrated Traditional Chinese and Western Medicine on Oncology, 315040 Ningbo, China.
EM XEnWang@tom.com
CR Tolcher AW, Patnaik A, Papadopoulos KP, RascoDW, Becerra CR, Allred AJ, Orford K, Aktan G, Ferron-Brady G, Ibrahim N, Gauvin J, Motwani M, Cornfeld M, 2015, Phase I study of the MEK inhibitor trametinib in combination with the AKTinhibitor afuresertib in patients with solid tumors and multiple myeloma. Cancer Chemother Pharmacol 75:183–189
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 499
EP 505
DI 10.1007/s12253-018-0545-y
PG 7
ER
PT J
AU Khan, SM
Qadri, Q
Makhdoomi, JM
Wani, AM
Malik, AA
Niyaz, M
Masoodi, RSh
Andrabi, IK
Ahmad, R
Mudassar, S
AF Khan, S Mosin
Qadri, Qurteeba
Makhdoomi, J Mudasir
Wani, A Muneer
Malik, A Aejaz
Niyaz, Madiha
Masoodi, R Shariq
Andrabi, I Khurshid
Ahmad, Rauf
Mudassar, Syed
TI RET/PTC Gene Rearrangements in Thyroid Carcinogenesis: Assessment and Clinico-Pathological Correlations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Thyroid Cancer; TSH; Papillary thyroid cancer; Kashmir Valley; RET/PTC rearrangement
ID Thyroid Cancer; TSH; Papillary thyroid cancer; Kashmir Valley; RET/PTC rearrangement
AB Rearranged during transfection (RET) is a proto oncogene implicated in thyroid carcinogenesis of papillary type (PTC). The RET proto-oncogene in PTC is constitutively activated by fusion of its tyrosine kinase domain with the 5 ´region of another gene thereby generating chimeric products collectively named RET/PTCs. RET/PTC1 and RET/PTC3 are best characterized among all RET/PTC rearrangements. Kashmir valley has witnessed an alarming increase in thyroid cancer incidence in young women. Therefore, we investigated the occurrence of RET/PTC 1 & 3 rearrangements by semi quantitative and qPCR in thyroid cancer patients (n = 48) of Kashmiri population and interrelated results with various clinicopathological characteristics. We observed that all the RET/PTC rearrangements were confined to PTC cases (10/40). Presence of RET/PTC rearrangement significantly correlated with gender, elevated TSH levels and lymph node metastasis. Overall, our study advocates that RET/PTC3 rearrangement is a frequent event in the carcinogenesis of thyroid gland in Kashmiri population although a study with a larger sample size is needed to get a clear scenario.
C1 [Khan, S Mosin] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Qadri, Qurteeba] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Makhdoomi, J Mudasir] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Wani, A Muneer] Sher-I-Kashmir Institute of Medical Sciences, Department of General and Minimal Invasive Surgery, 190011 Soura, Srinagar, India.
[Malik, A Aejaz] Sher-I-Kashmir Institute of Medical Sciences, Department of General and Minimal Invasive Surgery, 190011 Soura, Srinagar, India.
[Niyaz, Madiha] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Masoodi, R Shariq] Sher-I-Kashmir Institute of Medical Sciences, Department of Endocrinology, 190011 Soura, Srinagar, India.
[Andrabi, I Khurshid] University of Kashmir, Department of Biotechnology, 190006 Hazratbal, Srinagar, India.
[Ahmad, Rauf] SMHS Govt. Superspeciality Hospital, Department of ENT, 190010 Karan Nagar, Srinagar, India.
[Mudassar, Syed] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
RP Mudassar, S (reprint author), Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, India.
EM syed.mudassar@skims.ac.in
CR Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R, 2013, Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol 2013:1–10. https:// doi.org/10.1155/2013/965212
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Santoro M, Carlomagno F, 2013, Central role of RET in thyroid cancer. Cold Spring Harb Perspect Biol 5:1–17. , DOI 10. 1101/cshperspect.a009233
Kurokawa K, Kawai K, Hashimoto M, Ito Y, Takahashi M, 2003, Cell signalling and gene expression mediated by RET tyrosine kinase. J Intern Med 253:627–633
Nikiforov YE, 2002, RET/PTC rearrangement in thyroid tumors. Endocr Pathol 13:3–16. , DOI 10.1385/EP:13:1:03
Tong G-X, Mody K, Wang Z, Hamele-Bena D, Nikiforova MN, Nikiforov YE, 2015, Mutations of TSHR and TP53 genes in an aggressive clear cell follicular carcinoma of the thyroid. Endocr Pathol 26:315–319 , DOI 10.1007/s12022-015-9388-1
Khan MS, Pandith AA, Azad N, Hussain MU, Masoodi SR, Wani KA, Andrabi KI, Mudassar S, 2014, Impact of molecular alterations of BRAF in the pathogenesis of thyroid cancer. Mutagenesis 29:131–137
Khan MS, Pandith AA, HussainMU, Iqbal M, Khan NP,Wani KA, Masoodi SR,Mudassar S, 2013, Lack of mutational events of RAS genes in sporadic thyroid cancer but high risk associated with HRAS T81C singlenucleotide polymorphism, case–control study). Tumor Biol 34:521–529
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HamataniK, EguchiH, Ito R,MukaiM, Takahashi K, TagaM, Imai K, Cologne J, Soda M, Arihiro K, Fujihara M, Abe K, Hayashi T, Nakashima M, Sekine I, Yasui W, Hayashi Y, Nakachi K, 2008, RET/PTC rearrangements preferentially occurred in papillary thyroid Cancer among atomic bomb survivors exposed to high radiation dose. Cancer Res 68:7176–7182 , DOI 10.1158/0008- 5472.CAN-08-0293
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 507
EP 513
DI 10.1007/s12253-018-0540-3
PG 7
ER
PT J
AU El-Bolkainy, T
Mohamed, G
Badawy, O
AF El-Bolkainy, Tarek
Mohamed, Ghada
Badawy, Omnia
TI Precursor Lesions of the Vocal Cord: a Study on the Diagnostic Role of Histomorphology, Histometry and Ki-67 Proliferation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Laryngeal cancer; Dysplasia; Dyskeratosis; Histometry; Ki-67 labeling index
ID Laryngeal cancer; Dysplasia; Dyskeratosis; Histometry; Ki-67 labeling index
AB The precise typing of precursor lesions of squamous cell carcinoma of vocal cord is of vital importance since it determines the line of therapy and prognosis. The aim of the present study is to evaluate the possible value of the types of dyskeratosis, histometry and cell proliferation rate in discriminating these lesions. The present retrospective study was based on 145 patients, classified according to the updated 2017 WHO system and included: Low-grade dysplasia (24 cases), high-grade dysplasia (53 cases), carcinoma in situ (33 cases) and microinvasive carcinomas (35 cases). Cell proliferation was assessed by immunoreactivity to Ki-67. For histometry and quantitation of Ki-67 proliferation rate, an image analysis system was used (Leica LAS, Wetzlar, Germany). Epithelial pearls (cell nests) were commonly observed in microinvasive carcinoma (82.9%) than high-grade dysplasia (5.9%). The median epithelial thickness, as well as, proliferation rate showed a significant increase according to the grade of the lesion. It is concluded that dyskeratosis pattern, histometry and Ki-67proliferation rate are valuable parameters to characterize precursor lesions. The presence of epithelial pearls, thickness > 450 μm and Ki-67 > 40% denote high risk lesions that require adequate excision and/or radiotherapy.
C1 [El-Bolkainy, Tarek] Cairo University, National Cancer Institute, Department of PathologyGiza, Egypt.
[Mohamed, Ghada] Cairo University, National Cancer Institute, Department of PathologyGiza, Egypt.
[Badawy, Omnia] Cairo University, National Cancer Institute, Department of PathologyGiza, Egypt.
RP Badawy, O (reprint author), Cairo University, National Cancer Institute, Department of Pathology, Giza, Egypt.
EM omniabadawy75@gmail.com
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386
Globocan, 2012, Estimated Cancer incidence, mortality and prevalence worldwide: Sources, methods and major patterns. http:// globocan.iarc.fr/Pages/fact_sheets_population.aspx?country=818
Kumar V, Abbas A, Aster J, 2018, Robbins basic pathology, 10th edn. Elsevier Inc, Philadelphia, pp 546–547
Fletcher C, ed,, 2013, Diagnostic histopathology of tumors, 4th edn. Elsevier, Saunders, Philadelphia, p 171
Nayar R,WilburD, eds,, 2015, The Bethesda system for Reporting cervical cytology, ed 3. Definitions, criteria, and explanatory notes. Springer, New York
Barnes L, Eveson IW, Reichart P, Sidransky D, eds,, 2005, WHO pathology and genetics, head and neck tumors, 3rd edition, p120, IARC. Lyon, France
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, 2017, WHO classification of head and neck tumors, 4th edition, p 91–93. IARC, Lyon
Gnepp DR, ed,, 2009, Diagnostic surgical pathology of head and neck, 2nd edn. Saunders Elsevier, Philadelphia
Gale N, Michaels L, Luzar B, Poljak M, Zidar N, Fischinger J, Cardesa A, 2009, Current review on squamous intraepithelial lesions of the larynx. Histopathology 54:639–656
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Grissman JD, Zarbo RJ, Drozdowicz S, 1988, Carcinoma in situ and microinvasive squamous carcinoma of the laryngeal glottis. Arch Otolaryngol Head Neck Surg 114:299–307
Barnes L, ed,, 2009, Surgical pathology of head and neck, 3rd edn. Informa Health care, New York
Arens C, Glanz H, Wonckhaus J, Hersemeyer K, Kraft M, 2007, Histologic assessment of epithelial thickness in early laryngeal cancer or precursor lesions and its impact on endoscopic imaging. Eur Arch Otorhinolaryngol 264:645–649
Mondal D, Saha K, Datta C, Chatterjee U, Sengupta A, 2013, Ki- 67, p27, p53 expression in squamous epithelial lesions of larynx. Indian J Otolaryngol Head Neck Surg 65:126–133
Amin MB et al, 2017, AJCC cancer staging manual. Springer- Verlag, New York
Weller MD, Nankivell PC, McConkey C, Paleri V, Mehanna HM, 2012, The risk and interval to malignancy of patients with laryngeal dysplasia; a systematic review of case series andmeta-analysis. Clin Otolaryngol 35(5):364–372
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Pavlovic B, Djukic V, Milovanovic J, Tomanovic N, Milovanovic A, Trivic A, 2013, Morphometric analysis of Ki-67 and p16 expression in laryngeal precursor lesions. Eur Arch Otorhinolaryngol 270:1405–1410
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 515
EP 520
DI 10.1007/s12253-018-0560-z
PG 6
ER
PT J
AU Yan, Y
Zhang, L
Tan, L
Ma, X
Yong, Z
Shao, Sh
Liu, J
Xue, Ch
Li, Z
Zhang, X
Drokow, KE
Shi, X
Ren, J
AF Yan, Yanli
Zhang, Long
Tan, Li
Ma, Xiaowei
Yong, Zhang
Shao, Shuai
Liu, Jiaxin
Xue, Chaofan
Li, Zongfang
Zhang, Xiaozhi
Drokow, Kwateng Emmanuel
Shi, Xiaoting
Ren, Juan
TI Endocrine Therapy for Ductal Carcinoma In Situ (DCIS) of the Breast with Breast Conserving Surgery (BCS) and Radiotherapy (RT): a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ductal carcinoma in situ (DCIS); Endocrine therapy; Meta-analysis
ID Ductal carcinoma in situ (DCIS); Endocrine therapy; Meta-analysis
AB The management of ductal carcinoma in situ (DCIS) with endocrine therapy remains controversial. A meta-analysis was conducted to evaluate the role of endocrine therapy for DCIS with breast conserving surgery (BCS) and radiotherapy (RT). A total of 7 articles with randomized controlled trials were included. Five articles compared the effects of BCS and RT followed by tamoxifen (TAM) or not (BCS + RT + TAM vs BCS + RT) and 2 compared the effects of TAM and anastrozole (ANA). TAM obviously reduced the rates of recurrence of ipsilateral breast cancer (IBCR), recurrence of contralateral breast cancer (CBCR), recurrence of ipsilateral invasive breast cancer (IBCR-INV) and recurrence of contralateral DCIS (CBCR-DCIS), and increased the rate of event-free survival (EFS). While ANA reduced the rates of CBCR and recurrence of contralateral invasive breast cancer (CBCR-INV). Patients with ANA had higher incidence of arthralgia, osteoporosis, hypercholesteremia, headache and vaginal dryness, but lower incidence of deep-vein thrombosis, pulmonary embolism, vasomotor or gynaecological, hot flushes, vaginal haemorrhage, vaginal discharge and vaginal candidiasis than TAM. In conclusion, DCIS patients with positive hormone receptors should be recommended to receive endocrine therapy. Selection of TAM or ANA is based on clinical characteristics and underlying disease of patients, as well as the side-effects of drugs.
C1 [Yan, Yanli] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Zhang, Long] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi Province, China.
[Tan, Li] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Ma, Xiaowei] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Yong, Zhang] Xi’an Children Hospital, Department of Orthopedics, 710000 Xi’an, Shaanxi Province, China.
[Shao, Shuai] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Liu, Jiaxin] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Xue, Chaofan] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Li, Zongfang] Second Affiliated Hospital of Xi’an Jiaotong University, Department of Surgery, 710004 Xi’an, Shaanxi Province, China.
[Zhang, Xiaozhi] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi Province, China.
[Drokow, Kwateng Emmanuel] Xi’an Jiaotong University, First Affiliated Hospital of Medical College, 710061 Xi’an, Shaanxi Province, China.
[Shi, Xiaoting] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi Province, China.
[Ren, Juan] First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, Shaanxi Province, China.
RP Ren, J (reprint author), First Affliated Hospital, Xi’an Jiaotong University, Department of Oncology Radiotherapy, 710061 Xi’an, China.
EM 869491533@qq.com
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Staley H, McCallum I, Bruce J, 2014, Postoperative tamoxifen for ductal carcinoma in situ: Cochrane systematic review and metaanalysis. Breast, Edinburgh, Scotland, 23(5):546–551. https://doi. org/10.1016/j.breast.2014.06.015
Houghton J, GeorgeWD, Cuzick J, Duggan C, Fentiman IS, Spittle M, 2003, Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 362(9378): 95–102
Cuzick J, Sestak I, Pinder SE, Ellis IO, Forsyth S, Bundred NJ, Forbes JF, Bishop H, Fentiman IS, George WD, 2011, Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. Lancet Oncol. 12(1):21–29. , DOI 10.1016/S1470- 2045(10)70266-7
Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T, Group AT, 2002, Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359(9324):2131–2139
Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, Group AT, 2005, Results of the ATAC, Arimidex, tamoxifen, alone or in combination, trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 365(9453):60–62. , DOI 10.1016/ S0140-6736(04)17666-6
Breast International Group 1-98 Collaborative G, Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I,Wardley A, Price KN, Goldhirsch A, 2005, A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757. , DOI 10.1056/NEJMoa052258
Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, 2017, NCCN guidelines insights: breast Cancer, version 1.2017. Journal of the National Comprehensive Cancer Network. Jnccn 15(4):433– 451
Margolese RG, Cecchini RS, Julian TB, Ganz PA, Costantino JP, Vallow LA, Albain KS, Whitworth PW, Cianfrocca ME, Brufsky AM, Gross HM, Soori GS, Hopkins JO, Fehrenbacher L, Sturtz K, Wozniak TF, Seay TE, Mamounas EP, Wolmark N, 2015, Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy, NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 387:849–856. , DOI 10.1016/S0140-6736(15, 01168-X
Forbes JF, Sestak I, Howell A, Bonanni B, Bundred N, Levy C, von Minckwitz G, Eiermann W, Neven P, Stierer M, Holcombe C, Coleman RE, Jones L, Ellis I, Cuzick J, investigators I-I, 2015, Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ, IBIS-II DCIS): a doubleblind, randomised controlled trial. Lancet. , DOI 10.1016/ S0140-6736(15)01129-0
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 521
EP 531
DI 10.1007/s12253-018-0553-y
PG 11
ER
PT J
AU Li, W
Meng, Z
Zou, T
Wang, G
Su, Y
Yao, Sh
Sun, X
AF Li, Weichao
Meng, Zengdong
Zou, Tiannan
Wang, Gang
Su, Yijing
Yao, Shaoping
Sun, Xianrun
TI MiR-374a Activates Wnt/β-Catenin Signaling to Promote Osteosarcoma Cell Migration by Targeting WIF-1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma (OS); miR-374a; Migration; Wnt inhibitory factor-1 (WIF-1); Wnt/β-catenin; Signaling pathway
ID Osteosarcoma (OS); miR-374a; Migration; Wnt inhibitory factor-1 (WIF-1); Wnt/β-catenin; Signaling pathway
AB MiR-374a was proved to take part in the initiation and development of several cancers. However, the molecular mechanism of miR-374a in osteosarcoma (OS) cells remains unclear. The aim of our research was to investigate the role of miR-374a in OS cells migration and clarify the potential mechanisms. Quantitative real-time PCR (qRT-PCR) and western blot analysis were applied to evaluate the expression of miR-374a and Wnt inhibitory factor-1 (WIF-1). Bioinformatical methods and luciferase reporter assay were carried out to predict and confirm the combination of miR-374a and WIF-1. Transwell and wound healing assays were performed to detect the migration capacity of OS cells. Lithium chloride (LiCl) was used to investigate the role of LiCl-activated Wnt/β-catenin signaling pathway in regulating cell migration. Our studies revealed that miR-374a was upregulated whereas WIF-1 was down-regulated in OS cells. Besides, WIF-1 was the target of miR-374a by performing luciferase reporter assay. By transfection of miR-374a inhibitor and/or WIF-1 siRNA to OS cells, we found that miR-374a promoted the migration of OS cells. In addition, the inhibition of WIF-1 abolished the miR-374a inhibitor-induced migration suppression of OS cells. LiCl experiment revealed that miR-374a promoted OS cells migration by regulating Wnt/β-catenin signaling. In conclusion, miR-374a promotes OS cells migration by activating Wnt/β-catenin signaling pathway via targeting WIF-1.
C1 [Li, Weichao] Kunming University of Science and Technology, Medical School, 650500 Kunming, China.
[Meng, Zengdong] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
[Zou, Tiannan] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
[Wang, Gang] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
[Su, Yijing] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
[Yao, Shaoping] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
[Sun, Xianrun] The First Affiliated Hospital of Kunming Medical College, Department of Surgery, No. 157 Jinbi Road, 650032 Kunming, China.
RP Yao, Sh (reprint author), The First Affiliated Hospital of Kunming Medical College, Department of Surgery, 650032 Kunming, China.
EM gukeyshp@sina.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 533
EP 539
DI 10.1007/s12253-018-0556-8
PG 7
ER
PT J
AU Xuan, Z
Huang, J
Gao, L
Wang, Y
Wang, J
Sun, Y
AF Xuan, Zhuoqi
Huang, Jianming
Gao, Lin
Wang, Yong
Wang, Jiandong
Sun, Yueming
TI Receptor Tyrosine Kinase EphB3: a Prognostic Indicator in Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; EphB3; Hypermethylation; Lymph node metastasis; TNM stage
ID Colorectal cancer; EphB3; Hypermethylation; Lymph node metastasis; TNM stage
AB Although EphB3 expression is down-regulated in colorectal cancer (CRC) cells compared with normal intestinal epithelial cells, the relationship between EphB3 expression and clinicopathological parameters in CRC is unclear. We examined EphB3 expression in 128 CRC tissue specimens and in 19 adenoma specimens using immunohistochemistry. The relationships between EphB3 expression and clinicopathological parameters, KRAS mutations, BRAF V600E mutation, MSI and survival were evaluated using Spearman’s rank correlation and Kaplan–Meier survival analyses, respectively. CpG methylation in the EphB3 promoter was examined in four human CRC cell lines and tissues. EphB3 was strongly expressed in all normal intestinal epithelial cells (128/128) and adenoma cells (19/19). In CRC tumor cells, EphB3 expression was negative or weak in 41.4% (53/128), moderate in 26.6% (34/128), and strong in 32.0% (41/128) of samples. EphB3 expression was negatively associated with invasive depth (P = 0.016, rs = −0.213), lymph node metastasis (P = 0.000, rs = −0.490), and TNM stage (P = 0.000, rs = −0.390), and was positively associated with poor differentiation (P = 0.001, rs = 0.290), BRAF V600E mutation (P = 0.008, rs = 0.235), and longer overall survival (P < 0.001). In multivariate analysis, EphB3 expression (P = 0.007) and lymph node metastasis (P < 0.001) were independent prognostic factors for poor survival. Hypermethylation of the EphB3 promoter was detected in cell lines and CRC tissues. EphB3 is down-regulated in CRC compared to normal mucosa. Hypermethylation of CpG island is contributed to downregulation of EphB3 in CRC. EphB3 expression in tumor cells may be a useful prognostic indicator for patients with CRC.
C1 [Xuan, Zhuoqi] The First Affiliated Hospital of Nanjing Medical University, Department of Colorectal Surgery, 210029 Nanjing, Jiangsu, China.
[Huang, Jianming] The Jiangyin People’s Hospital, Department of Gastrointestinal Surgery, 214400 Jinagsu, China.
[Gao, Lin] The Jiangyin People’s Hospital, Department of Gastrointestinal Surgery, 214400 Jinagsu, China.
[Wang, Yong] The First Affiliated Hospital of Nanjing Medical University, Department of Colorectal Surgery, 210029 Nanjing, Jiangsu, China.
[Wang, Jiandong] Nanjing University School of Medicine, Jinling Hospital, Department of Pathology, No.305, Zhong San Dong Lu, 210002 Nanjing, China.
[Sun, Yueming] The First Affiliated Hospital of Nanjing Medical University, Department of Colorectal Surgery, 210029 Nanjing, Jiangsu, China.
RP Wang, J (reprint author), Nanjing University School of Medicine, Jinling Hospital, Department of Pathology, 210002 Nanjing, China.
EM jd_wang@outlook.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 541
EP 549
DI 10.1007/s12253-018-0562-x
PG 9
ER
PT J
AU Niyaz, M
Khan, SM
Wani, AR
Shah, JO
Mudassar, S
AF Niyaz, Madiha
Khan, S Mosin
Wani, A Rauf
Shah, J Omar
Mudassar, Syed
TI Sonic Hedgehog Protein is Frequently Up-Regulated in Pancreatic Cancer Compared to Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sonic hedgehog; Hedgehog signalling pathway; Protein expression; Western blotting; Colorectal cancer; Pancreatic cancer
ID Sonic hedgehog; Hedgehog signalling pathway; Protein expression; Western blotting; Colorectal cancer; Pancreatic cancer
AB Sonic hedgehog (SHH) is a secreted protein which functions in autocrine or paracrine fashion on target cells to activate hedgehog (HH) signalling cascade responsible for growth and proliferation. This study is an attempt to understand the expression dynamics of SHH protein in colon, rectal and pancreatic cancers. Protein expression of SHH was studied by Western Blotting in the histologically confirmed colon, rectum and pancreatic cancer tissue samples along with their adjacent normal tissues. Only 31.4% (11 of 35) and 26.9% (7 of 26) of colon and rectal cancer cases respectively showed an increase in SHH expression in tumours compared to 72.7% (24 of 33) of the pancreatic cancer cases when compared with their adjacent normal tissues. Our results suggest that SHH may have a strong role in the predisposition of Pancreatic cancer and could possibly be used as a diagnostic or prognostic biomarker.
C1 [Niyaz, Madiha] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Khan, S Mosin] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
[Wani, A Rauf] Sher-I-Kashmir Institute of Medical Sciences, Department of General and Minimal Invasive Surgery, 190011 Soura, Srinagar, India.
[Shah, J Omar] Sher-I-Kashmir Institute of Medical Sciences, Department of Surgical Gastroenterology, 190011 Soura, Srinagar, India.
[Mudassar, Syed] Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, Srinagar, India.
RP Mudassar, S (reprint author), Sher-I-Kashmir Institute of Medical Sciences, Department of Clinical Biochemistry, 190011 Soura, India.
EM syed.mudassar@skims.ac.in
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 551
EP 557
DI 10.1007/s12253-018-00564-2
PG 7
ER
PT J
AU Zhang, K
Li, C
Liu, J
Li, Z
Ma, Ch
AF Zhang, Ke
Li, Cuilin
Liu, Jianqiu
Li, Zhi
Ma, Chao
TI Down-Regulation of APTR and it’s Diagnostic Value in Papillary and Anaplastic Thyroid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE APTR; Papillary thyroid cancer (PTC); Anaplastic thyroid cancer (ATC); ROC; Diagnosis
ID APTR; Papillary thyroid cancer (PTC); Anaplastic thyroid cancer (ATC); ROC; Diagnosis
AB APTR has been employed as a potential biomarker attributing to it was involved in carcinogenesis and malignancy’s progression. However, the roles of APTR in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) are unclear. In the present study, we aimed to explore the relative expression of APTR in PTC and ATC tissues and the relation between APTR expression and PTC clinicopathological features. We analyzed APTR expression in PTC and ATC by investigating data obtained from the Gene Expression Omnibus (GEO) database. Then, we tested 76-pair PTC and adjacent normal samples by qRT-PCR, and the result was in accordance with the analysis in GEO datasets. Chi-square (χ2) analysis was employed to evaluate the association between APTR and PTC clinical features. These results showed that APTR was negatively related to TNM stages, distant metastasis. In addition, we further evaluated the feasibility of using APTR to detect PTC and ATC patients by the receiver operating characteristic (ROC) and the area under curve (AUC). These findings implied that down-regulation of APTR is correlated with tumorigenesis, also indicated that the potential diagnostic value of APTR for detecting PTC and ATC patients.
C1 [Zhang, Ke] Central South University, Xiangya Hospital, Department of Clinical Pharmacology, 410008 Changsha, China.
[Li, Cuilin] ZhuZhou Central Hospital, Department of Pharmacy, 410078 ZhuZhou, China.
[Liu, Jianqiu] Central South University, Xiangya Hospital, Department of Clinical Pharmacology, 410008 Changsha, China.
[Li, Zhi] Central South University, Xiangya Hospital, Department of Clinical Pharmacology, 410008 Changsha, China.
[Ma, Chao] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of Hepatopancreatobiliary Surgery, Tongbai Road #195, 450007 Zhengzhou, Henan, China.
RP Ma, Ch (reprint author), Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of Hepatopancreatobiliary Surgery, 450007 Zhengzhou, China.
EM machao813@163.com
CR Siegel RL, Miller KD, Jemal A, 2017, Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 559
EP 565
DI 10.1007/s12253-018-0561-y
PG 7
ER
PT J
AU Nterma, P
Panopoulou, E
Papadaki-Petrou, E
Assimakopoulou, M
AF Nterma, Pinelopi
Panopoulou, Eleni
Papadaki-Petrou, Eleni
Assimakopoulou, Martha
TI Immunohistochemical Profile of Tumor Suppressor Proteins RASSF1A and LATS1/2 in Relation to p73 and YAP Expression, of Human Inflammatory Bowel Disease and Normal Intestine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RASSF1A; LATS1/2; HIPPO pathway; Human inflammatory bowel disease; Ulcerative colitis; Crohn’s disease
ID RASSF1A; LATS1/2; HIPPO pathway; Human inflammatory bowel disease; Ulcerative colitis; Crohn’s disease
AB The intestinal neoplastic transformation is a possible risk of chronic inflammatory bowel disease (IBD). Previous evidence in mice IBD provides a role for the RAS-association domain family tumor suppressor protein 1 A (RASSF1A), in the repairing process following mucosa epithelium damage, through cooperation with the HIPPO-signaling molecules p73, and YAP. HIPPO pathway which has been implicated in stem cell activity includes as key components for signal transduction the large tumor suppressor homology Ser/Thr kinases LATS1/2. The aim of this study was to assess immunohistochemically, using specific antibodies, the RASSF1A and LATS1/2 expression patterns in a cohort of patients with IBD including 52 ulcerative colitis (UC), 24 Crohn’s disease (CD) and 24 IBD unclassified (IBD-U), compared with normal intestine from non-IBD patients (control group). The relationship between subtypes of IBD and RASSF1A and LATS1/2 expression, both individually and related to p73 and YAP/ pYAP(Ser127) proteins was also investigated. Quantitative analyses of the immunohistochemical findings in mucosa cells revealed a significantly decreased expression in UC and IBD-U for RASSF1A expression and a significantly elevated expression in UC, IBD-U, and CD for LATS1/2 expression compared with normal mucosa (P < 0.05).However, ROC curve analysis showed that only LATS1/2 could differentiate IBD from control group. RASSF1A expression was significantly correlated with LATS1/2 in UC with dysplasia (P < 0.0001), and p73 in UC (P < 0.001), and IBD-U(P < 0.02). The expression of all proteins did not differ significantly between subtypes of IBD (P ≥ 0.05). RASSF1A-LATS1/2 co-expression was mainly observed in IBD samples. These findings suggest that tumor suppression proteins RASSF1A and LATS1/2 may be involved in the pathogenesis of human IBD and imply a potential cooperation of RASSF1A, and HIPPO signaling pathways in human bowel inflammation.
C1 [Nterma, Pinelopi] University of Patras, School of Medicine, Department of Anatomy, Histology and Embryology, Biomedical Sciences Research Building, 1 Asklipiou, Gr-26504 Rion, Greece.
[Panopoulou, Eleni] General Hospital Agios Andreas, Department of PathologyPatras, Greece.
[Papadaki-Petrou, Eleni] University of Patras, School of Medicine, Department of Anatomy, Histology and Embryology, Biomedical Sciences Research Building, 1 Asklipiou, Gr-26504 Rion, Greece.
[Assimakopoulou, Martha] University of Patras, School of Medicine, Department of Anatomy, Histology and Embryology, Biomedical Sciences Research Building, 1 Asklipiou, Gr-26504 Rion, Greece.
RP Assimakopoulou, M (reprint author), University of Patras, School of Medicine, Department of Anatomy, Histology and Embryology, Gr-26504 Rion, Greece.
EM massim@upatras.gr
CR Maher MM, 2012, Inflammatory bowel disease: review and future view. Front Biosci, Elite Ed, 4:1638–1647
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 567
EP 574
DI 10.1007/s12253-018-00575-z
PG 8
ER
PT J
AU He, D
Liu, L
Wang, Y
Sheng, M
AF He, Dongyun
Liu, Li
Wang, Yang
Sheng, Minjia
TI A Novel Genes Signature Associated with the Progression of Polycystic Ovary Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Polycystic ovary syndrome; Microarray; WGCNA; Interaction network
ID Polycystic ovary syndrome; Microarray; WGCNA; Interaction network
AB To identify genes involving in the pathogenesis of polycystic ovary syndrome (PCOS). In this study, the comprehensive analysis of GSE8157 was downloaded. Overlapping genes of differentially expressed genes (DEGs) were identified, and enrichment analysis for these genes was performed. A modular network of differentially expressed genes was constructed by weighted gene co-expression network analyses (WGCNA), and a total of 322 differentially expressed genes in 5 stable modules were screened. The correlations of genes of the stable modules in BioGRID 3.4, STRING 10.5, HPRD9 databases were screened, and the interaction network of 104 DEGs was constructed. In addition, some genes and the key words were searched in CTD. A total of 596 differentially expressed genes were screened, including 379 genes that were up-regulated in case group and down-regulated in control group and treat group, and 217 genes that were down-regulated in case group and up-regulated in control group and treat group. The differentially expressed genes were enriched in PPAR signaling pathway, Neuroactive ligand-receptor interaction, cAMP signaling pathway, of which pathways were involved in the cancer development. Finally, 7 important target genes were identified, such as APOC3 was interacted with pioglitazone, ADCY2 involved in cAMP signaling pathway, and the genes (C3AR1, HRH2, GRIA1, MLNR and TAAR2) involved in neuroactive ligand-receptor interaction. In addition, the important target genes were significantly differential expression. These results implied that the 7 important target genes were played an important role in the development and progression of PCOS. Our study implied that genes had played a key role in the development and progression of PCOS, the results showed that microarray can be use as a method for the discovery of new biomarkers and therapeutic targets for PCOS.
C1 [He, Dongyun] China-Japan Union Hospital of Jilin University, Department of Gynecology and Obstetrics, No.126, Xiantai Road, 130031 Changchun, China.
[Liu, Li] China-Japan Union Hospital of Jilin University, Department of Gynecology and Obstetrics, No.126, Xiantai Road, 130031 Changchun, China.
[Wang, Yang] The Affiliated Hospital of Changchun University of Chinese Medicine, Department of Dermatology, 130031 Changchun, China.
[Sheng, Minjia] China-Japan Union Hospital of Jilin University, Department of Gynecology and Obstetrics, No.126, Xiantai Road, 130031 Changchun, China.
RP Sheng, M (reprint author), China-Japan Union Hospital of Jilin University, Department of Gynecology and Obstetrics, 130031 Changchun, China.
EM angela83666@163.com
CR Shahebrahimi K, Jalilian N, Bazgir N, Rezaei M, 2016, Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome. Indian J EndocrinolMetab 20(6):805–809
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Medina IR, Lubovacpilav Z, 2016, Gene co-expression network analysis for identifying modules and functionally enriched pathways in type 1 diabetes. PLoS One 11(6):e0156006
BJ B, C S TR, L B AB, M L RO, DH L, J B VW, 2008, The BioGRID interaction database: 2008 update. Nucleic Acids Res 36(Database issue):637–640
Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, 2017, The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res 45(Database issue):D362–D368
Mohmood R, Ramachandra YI, KrishnaV, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Kashyap MK, 2009, Human protein reference database - 2009 update
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Jong MC, Hofker MH, Havekes LM, 1999, Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol 19(3):472
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Samanci C,Alis D,Ustabasioglu FE, Ozmen E, Ucar AK, Aslan M, Habibi HA, Bakan S, Ozcabi B, Evliyaoglu SO, 2016, Apparent diffusion coefficient measurement of ovarian stroma: a potential tool for the diagnosis of polycystic ovary syndrome. Diagn Interv Imaging 98(1):57–61
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 575
EP 582
DI 10.1007/s12253-019-00676-3
PG 8
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Inactivating Frameshift Mutations of HACD4 and TCP10L Tumor Suppressor Genes in Colorectal and Gastric Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Ikeda M, Kanao Y, Yamanaka M, Sakuraba H, Mizutani Y, Igarashi Y, Kihara A, 2008, Characterization of four mammalian 3- hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. FEBS Lett 582:2435–2440
Zhu S, Wang Z, Zhang Z, Wang J, Li Y, Yao L, Mei Q, Zhang W, 2014, PTPLAD2 is a tumor suppressor in esophageal squamous cell carcinogenesis. FEBS Lett 588:981–989
Nord H, Hartmann C, Andersson R, Menzel U, Pfeifer S, Piotrowski A, Bogdan A, Kloc W, Sandgren J, Olofsson T, Hesselager G, Blomquist E, Komorowski J, von Deimling A, Bruder CE, Dumanski JP, Diaz de Stahl T, 2009, Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array. Neuro-Oncology 11:803–818
Zuo J, Cai H,Wu Y, Ma H, JiangW, Liu C, Han D, Ji G, Yu L, 2014, TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma. Biochem Biophys Res Commun 446:61– 67
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Choi YJ, Kim MS, An CH, Yoo NJ, Lee SH, 2014, Regional bias of intratumoral genetic heterogeneity of nucleotide repeats in colon cancers with microsatellite instability. Pathol Oncol Res 20:965–971
Jo YS, Choi MR, Song SY, Kim MS, Yoo NJ, Lee SH, 2016, Frameshift mutations of HSPA4 and MED13 in gastric and colorectal cancers. Pathol Oncol Res 22:769–772
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 583
EP 584
DI 10.1007/s12253-018-0409-5
PG 2
ER
PT J
AU Jo, SY
Kim, SM
Yoo, JN
Lee, HS
AF Jo, Sol Yun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral Heterogeneity for Inactivating Frameshift Mutation of CYB5R2 Gene in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Jo, Sol Yun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Devaney JM, Wang S, Funda S, Long J, Taghipour DJ, Furbert- Harris P, Ittmann M, Kwabi-Addo B, 2013, Identification of novel DNA-methylated genes that correlate with human prostate cancer and high-grade prostatic intraepithelial neoplasia. Molecular cloning and characterization of p56dok-2 defines a new family of RasGAPbinding proteins. Prostate Cancer Prostatic Dis 16:292–300
X X, Zhao W, Tian F, Zhou X, Zhang J, Huang T, Hou B, Du C, Wang S, Mo Y, Yu N, Zhou S, You J, Zhang Z, Huang G, Zeng X, 2014, Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma. Tumour Biol 35:3755–3763
Choi YJ, Kim MS, An CH, Yoo NJ, Lee SH, 2014, Regional bias of intratumoral genetic heterogeneity of nucleotide repeats in colon cancers with microsatellite instability. Pathol Oncol Res 20:965–971
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Oh HR, An CH, Yoo NJ, Lee SH, 2015, Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in gastric and colorectal cancers. Pathol Oncol Res 21:713–718
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 585
EP 586
DI 10.1007/s12253-018-0406-8
PG 2
ER
PT J
AU Lee, HJ
An, HCh
Kim, SM
Yoo, JN
Lee, HS
AF Lee, Hwa Ju
An, Hyeok Chang
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral Heterogeneity of RPL22 Frameshift Mutation in Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Lee, Hwa Ju] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General SurgerySeoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Rao S, Lee SY, Gutierrez A, Perrigoue J, Thapa RJ, Tu Z, Jeffers JR, Rhodes M, Anderson S, Oravecz T, Hunger SP, Timakhov RA, Zhang R, Balachandran S, Zambetti GP, Testa JR, Look AT, Wiest DL, 2012, Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120: 3764–3773
Ferreira AM, Tuominen I, van Dijk-Bos K, Sanjabi B, van der Sluis T, van der Zee AG, Hollema H, Zazula M, Sijmons RH, Aaltonen LA, Westers H, Hofstra RM, 2014, High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors. Hum Mutat 35:1442–1445
Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PE, Teo AS, Cutcutache I, Zhang Z, LeeWH, Sia YY, Gao S, Ariyaratne PN, Ho A,Woo XY, Veeravali L, Ong CK, Deng N, Desai KV, Khor CC, Hibberd ML, Shahab A, Rao J,Wu M, Teh M, Zhu F, Chin SY, Pang B, So JB, Bourque G, Soong R, SungWK, Tean Teh B, Rozen S, Ruan X, Yeoh KG, Tan PB, Ruan Y, 2012, Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol 13:R115
Marusyk A, Almendro V, Polyak K, 2012, Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 12:323–334
Choi EJ, Kim MS, Song SY, Yoo NJ, Lee SH, 2017, Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability. Pathol Oncol Res 23:145–149
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 587
EP 588
DI 10.1007/s12253-018-0438-0
PG 2
ER
PT J
AU Zhang, Pb
Cui, J
AF Zhang, Peng-bo
Cui, Jing
TI Letter to the Editor Regarding the Article "Long Non-Coding RNA SPRY4-IT1 Can Predict Poor Prognosis in Digestive System Malignancies: a Meta-Analysis"
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Zhang, Peng-bo] Kunming University of Science and Technology, Medical SchoolKunming, Chenggong, China.
[Cui, Jing] Kunming General Hospital, Department of PathologyKunming, Chenggong, China.
RP Zhang, Pb (reprint author), Kunming University of Science and Technology, Medical School, Kunming, China.
EM 1518918082@qq.com
CR Sun C, Ding Y, Wang S, Hu W, 2017, Long Non-Coding RNA SPRY4-IT1 Can Predict Poor Prognosis in Digestive System Malignancies: aMeta-Analysis. Pathology & Oncology Research:1–7
Egger M, Smith GD, Phillips AN, 1997, Meta-analysis: principles and procedures. Bmj British Medical Journal 315(7121):1533–1537
Lin KK, Sewell JL, 2013, The effects of race and socioeconomic status on immunomodulator and anti-tumor necrosis factor use among ambulatory patients with inflammatory bowel disease in the United States. Am J Gastroenterol 108(12):1824
Peng W, Wu G, Fan H, Wu J, Feng J, 2015, Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer. Tumor Biol 36(9):6751–6758
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 589
EP 590
DI 10.1007/s12253-018-0432-6
PG 2
ER
PT J
AU Plander, M
Szendrei, T
Vadvari,
Ivanyi, J
AF Plander, Mark
Szendrei, Tamas
Vadvari, Arpad
Ivanyi, Janos
TI Standard Dose of Ibrutinib is Effective in the Treatment of Bing-Neel Syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Plander, Mark] Vas County Markusovszky Hospital, Department of Hematology, Markusovszky str 5, 9700 Szombathely, Hungary.
[Szendrei, Tamas] Vas County Markusovszky Hospital, Department of Hematology, Markusovszky str 5, 9700 Szombathely, Hungary.
[Vadvari, Arpad] Markusovszky University Teaching Hospital, Department of RadiologySzombathely, Hungary.
[Ivanyi, Janos] Vas County Markusovszky Hospital, Department of Hematology, Markusovszky str 5, 9700 Szombathely, Hungary.
RP Plander, M (reprint author), Vas County Markusovszky Hospital, Department of Hematology, 9700 Szombathely, Hungary.
EM planderm@yahoo.com
CR Simon L, Fitsiori A, Lemal R, Dupuis J, Carpentier B, Boudin L et al, 2015, Bing-Neel syndrome, a rare complication of Waldenstrom’s macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French innovative leukemia organization, FILO). Haematologica 100:1587–1594
Castillo JJ, D’Sa S, Lunn MP, Minnema MC, Tedeschi A, Lansigan F et al, 2016, Central nervous system involvement by Waldenstrom macroglobulinaemia, Bing-Neel syndrome): a multi-institutional retrospective study. Br J Haematol 172:709–715
Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R et al, 2015, Ibrutinib in previously treated patients with Waldenstrom’s Macroglobulinemia. N Engl J Med 372:1430–1440
Bernard S, Goldwirt L, Amorim S, Brice P, Briere J, De Kerviler E et al, 2015, Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. Blood 126:1695–1698
Mason C, Savona S, Rini JN, Castillo JJ, Xu L, Hunter ZR et al, 2017, Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. Br J Haematol 179(2):339– 341
Cabannes-Hamy A, Lemal R, Goldwirt L, Poulain S, Amorin S, Perignon R et al, 2016, Efficacy of ibrutinib in the treatment of Bing-Neel syndrome. Am J Hematol 91:E17–E19
Boudin L, Patient M, Romeo E, Blade JS, de Jaureguiberry JP, 2018, Efficacy of ibrutinib as first-line treatment of tumoral Bing-Neel syndrome. Leuk Lymphoma 23:1–3
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 591
EP 592
DI 10.1007/s12253-018-0482-9
PG 2
ER
PT J
AU Stein, KM
Morris, KL
Martin, GM
AF Stein, K Matthew
Morris, K Lindsay
Martin, G Mike
TI Next-Generation Sequencing Identifies Novel RTK VUSs in Breast Cancer with an Emphasis on ROS1, ERBB4, ALK and NTRK3
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Stein, K Matthew] West Cancer CenterMemphis, TN, USA.
[Morris, K Lindsay] University of Tennessee, Health Science Center, College of MedicineMemphis, TN, USA.
[Martin, G Mike] West Cancer CenterMemphis, TN, USA.
RP Stein, KM (reprint author), West Cancer Center, Memphis, USA.
EM mkstein@westclinic.com
CR Blau CA, Ramirez AB, Blau S, Pritchard CC, Dorschner MO, Schmechel SC, Martins TJ, Mahen EM, Burton KA, Komashko VM, Radenbaugh AJ, Dougherty K, Thomas A, Miller CP, Annis J, Fromm JR, Song C, Chang E, Howard K, Austin S, Schmidt RA, Linenberger ML, Becker PS, Senecal FM, Mecham BH, Lee SI, Madan A, Ronen R, Dutkowski J, Heimfeld S, Wood BL, Stilwell JL, Kaldjian EP, Haussler D, Zhu J, 2016, A distributed network for intensive longitudinal monitoring in metastatic triple-negative breast Cancer. J Natl Compr Cancer Netw 14(1):8–17
Kurppa KJ, Denessiouk K, Johnson MS, Elenius K, 2016, Activating ERBB4 mutations in non-small cell lung cancer. Oncogene 35(10):1283–1291
Holla VR, Elamin YY, Bailey AM, Johnson AM, Litzenburger BC, Khotskaya YB, Sanchez NS, Zeng J, Shufean MA, Shaw KR, Mendelsohn J, Mills GB, Meric-Bernstam F, Simon GR, 2017, ALK: a tyrosine kinase target for cancer therapy. Cold Spring Harb Mol Case Stud 3(1):a001115
Stephens P, Edkins S, Davies H, Greenman C, Cox C, Hunter C, Bignell G, Teague J, Smith R, Stevens C, O'Meara S, Parker A, Tarpey P, Avis T, Barthorpe A, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Green A, Knowles M, Leung SY, Looijenga LHJ, Malkowicz B, Pierotti MA, Teh B, Yuen ST, Nicholson AG, Lakhani S, Easton DF,Weber BL, StrattonMR, Futreal PA,Wooster R, 2005, A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nat Genet 37:590–592
Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, Riggins GJ, Wang TL, Yan H, Gazdar A, Kern SE, Pennacchio L, Kinzler KW, Vogelstein B, Velculescu VE, 2006, Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat 27:1060–1061
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 593
EP 595
DI 10.1007/s12253-018-0550-1
PG 3
ER
PT J
AU Darre, T
Djiwa, T
Dare, S
Alassani, F
Napo-Koura, G
AF Darre, Tchin
Djiwa, Toukilnan
Dare, Sassil
Alassani, Fousseni
Napo-Koura, Gado
TI Difficult Causality Relationship between Colorectal Cancer and Schistosomiasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Colorectal cancer; Schistosomiasis; HIV; Carcinoma; Lymphoma
ID Colorectal cancer; Schistosomiasis; HIV; Carcinoma; Lymphoma
AB The purpose of the study was to determine the nature of the association between colorectal cancer and schistosomiasis infection. This was a retrospective and descriptive study of colorectal cancers and to identify cases associated with schistosomiasis. A total of 814 cases of rectal colorectal cancer were collected and 3 cases were associated with schistosomiasis. These are 2 cases of Liberkunian adenocarcinoma and one case of malt lymphoma. The patients were all farmers and from rural areas. A co-infection with HIV was found in his 3 patients. Our data show an extreme rarity of the association colorectal cancer and schistosomiasis; it seems difficult to conceive of a causal relationship.
C1 [Darre, Tchin] University Teaching Hospital of Lome, Department of PathologyLome, Togo.
[Djiwa, Toukilnan] University Teaching Hospital of Lome, Department of PathologyLome, Togo.
[Dare, Sassil] University Teaching Hospital of Lome, Department of Visceral SurgeryLome, Togo.
[Alassani, Fousseni] University Teaching Hospital of Lome, Department of Visceral SurgeryLome, Togo.
[Napo-Koura, Gado] University Teaching Hospital of Lome, Department of PathologyLome, Togo.
RP Darre, T (reprint author), University Teaching Hospital of Lome, Department of Pathology, Lome, Togo.
EM paolodarre@yahoo.fr
CR Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S, 2016, Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 4(9):e609–e616
Lapoile E, Bellaiche G, Boucard M et al, 2008, Cancer du rectum associe a une infection a Schistosoma hematobium. Gastroenterol Clin Biol 30(10):1225–1226
Darre T, Kpatcha K, Tchaou M et al, 2015, Histological aspect of urinary schistosomiasis in Togo: results of a cohort of 192 cases. Bull Soc Pathol Exot 108(2):124–125
Ferguson AR, 1911, Associated bilharziosis and primary malignant disease of the urinary bladder with observations on a series of forty cases. J Pathol Bacteriol 16(1):76–94
Gaye AM, Doh K, Thiam I, Bentefouet L, Woto-Gaye G, 2016, Schistosomiasis and cancer: a fortuitous association or relationships cause and effect. Bull Cancer 103(9):806–807
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2020
VL 26
IS 1
BP 597
EP 598
DI 10.1007/s12253-018-00566-0
PG 2
ER
PT J
AU Luo, P
Wu, S
Yu, Y
Ming, X
Li, Sh
Zuo, X
Tu, J
AF Luo, Ping
Wu, Sanyun
Yu, Yalan
Ming, Xinliang
Li, Shuo
Zuo, Xuelan
Tu, Jiancheng
TI Current Status and Perspective Biomarkers in AFP Negative HCC: Towards Screening for and Diagnosing Hepatocellular Carcinoma at an Earlier Stage
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE HCC; Biomarker; AFP-negative; Diagnose
ID HCC; Biomarker; AFP-negative; Diagnose
AB Hepatocellular carcinoma (HCC) is one of the most malignant cancer with high morbidity and mortality which lead to a serious burden to society. AFP (alpha-fetoprotein) is the most widely used serum biomarker to detect HCC worldwide. However, no AFP elevation have been found in many HCC and AFP analysis can’t be used to screen HCC in these cases. Currently, many studies have been carried out to find reliable biomarker in diagnosing AFP-negative HCC. Such biomarker would help the diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. In this review, we highlight the important role of biomarkers that can differentiate AFP-negative HCCs, and discuss their potential clinical applications as biomarkers for the diagnosis of AFP-negative HCC.
C1 [Luo, Ping] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Wu, Sanyun] Zhongnan Hospital of Wuhan University, Department of HematologyWuhan, China.
[Yu, Yalan] Zhongnan Hospital of Wuhan University, Department of HematologyWuhan, China.
[Ming, Xinliang] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Li, Shuo] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
[Zuo, Xuelan] Zhongnan Hospital of Wuhan University, Department of HematologyWuhan, China.
[Tu, Jiancheng] Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory MedicineWuhan, China.
RP Tu, J (reprint author), Zhongnan Hospital of Wuhan University, Department of Clinical Laboratory Medicine, Wuhan, China.
EM jianchengtu@whu.edu.cn
CR Gao T, Zhi J, Mu C, Gu S, Xiao J, Yang J,Wang Z, Xiang Y, 2018, One-step detection for two serological biomarker species to improve the diagnostic accuracy of hepatocellular carcinoma. Talanta 178:89–93
Cadier B, Bulsei J, Nahon P, Seror O, Laurent A, Rosa I, Layese R, Costentin C, Cagnot C, Durand-Zaleski I, Chevreul K, 2017, Early detection and curative treatment of hepatocellular carcinoma: a cost-effectiveness analysis in france and in the united states. Hepatology 65:1237–1248
Guo S, ChenW, Luo Y, Ren F, Zhong T, Rong M, Dang Y, Feng Z, Chen G, 2015, Clinical implication of long non-coding rna neat1 expression in hepatocellular carcinoma patients. Int J Clin Exp Pathol 8:5395–5402
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, 2011, Global cancer statistics. CA Cancer J Clin 61:69–90
Siegel RL, Miller KD, Jemal A, 2016, Cancer statistics, 2016. CA Cancer J Clin 66:7–30
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 599
EP 603
DI 10.1007/s12253-019-00585-5
PG 5
ER
PT J
AU Yuan, P
Ge, Y
Liu, X
Wang, Sh
Ye, Z
Xu, H
Chen, Z
AF Yuan, Peng
Ge, Yue
Liu, Xiao
Wang, Shen
Ye, Zhangqun
Xu, Hua
Chen, Zhiqiang
TI The Association of Androgen Receptor Expression with Renal Cell Carcinoma Risk: a Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Renal cell carcinoma; Androgen receptor; Prognosis; Targeted therapy
ID Renal cell carcinoma; Androgen receptor; Prognosis; Targeted therapy
AB The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance of androgen receptor expression in renal cell carcinoma. A computerized bibliographic search of Embase, the PubMed, and Web of Science combined with manual research between 1977 and 2017 was conducted to explore the association between androgen receptor expression and clinicopathological features of renal cell carcinoma. Data were analyzed by a meta-analysis using RevMan 5.3 analysis software. Eleven retrospective studies with 1839 renal cell carcinoma cases were finally included according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05). However, positive androgen receptor expression was demonstrated to be significantly associated with male patients, lower pathological grade, and earlier tumor stage of renal cell carcinoma (OR = 1.69, 95% CI = 1.30–2.19, P < 0.0001; OR = 2.06, 95% CI = 1.49–2.85, P < 0.0001; OR = 2.81, 95% CI = 1.30–6.12, P = 0.009; respectively). In conclusion, higher androgen receptor expression was correlated with male patients, low tumor grade and early stage of renal cell carcinoma. Based on current results, androgen receptor-inhibited target therapy for renal cell carcinoma patients may be of limited benefits and should be taken into more evaluations.
C1 [Yuan, Peng] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Ge, Yue] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Liu, Xiao] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Wang, Shen] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Ye, Zhangqun] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Xu, Hua] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
[Chen, Zhiqiang] Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, No.1095 Jie Fang Avenue, Hankou, 430030 Wuhan, China.
RP Chen, Z (reprint author), Huazhong University of Science and Technology, Tongji Medical School, Tongji Hospital, Department of Urology, 430030 Wuhan, China.
EM urol_chen@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 605
EP 614
DI 10.1007/s12253-019-00650-z
PG 10
ER
PT J
AU Moosavi, MS
Elham, Y
AF Moosavi, Mahdieh-Sadat
Elham, Yalda
TI Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Aquaporin; Cancer; Prognosis
ID Aquaporin; Cancer; Prognosis
AB All different types of metabolism of tumors are dependent on the flow of water molecules through the biological membrane, where fluid transfer interceded by aquaporins (AQPs) are the basis means for water entrance into the cells or outside them. Aquaporins play other roles including cellular migration, cellular expansion and cellular adhesion facilitation. Therefore, regulators of AQPs may be useful anticancer agents. Medline, Scopus, Embase, and Web of Sciences were searched. From among the papers found, 106 were related to the subject. All of the examined cancers in relation to AQP1 included adenoid cystic carcinoma, bladder, breast, cervical, colon, colorectal, hepatocellular, lung, ovarian, plural mesothelioma, prostate, renal cell carcinoma and squamous cell carcinoma. All of the studied cancers in relation with AQP3 included gastric, breast, prostate, lung, pancreas, skin, bladder, squamous cell carcinoma, cervical, adenoid cystic carcinoma, colon, colorectal, ovarian, and hepatocellular cancers and with regard to AQP5 were lung, squamous cell carcinoma, ovarian, adenoid cystic carcinoma, breast, colon, colorectal, hepatic, pancreas, gallbladder, prostate, and gastric cancers. Over or under-expression of AQP1, 3 and is exist in the mentioned cancers across different studies. Over-expression of AQP1, AQP3 and AQP5 is clearly associated with carcinogenesis, metastasis, reduced survival rate, lymph node metastasis, poorer prognosis, and cellular migration. Also, cancer treatments in relation to these markers suggest AQP reduction during the treatment.
C1 [Moosavi, Mahdieh-Sadat] Tehran University of Medical Sciences, Faculty of Dentistry, Dental Research Center, Dentistry Research Institute, Department of Oral MedicineTehran, Iran.
[Elham, Yalda] Tehran University of Medical Sciences, Faculty of Dentistry, Dental Research Center, Dentistry Research Institute, Department of Oral MedicineTehran, Iran.
RP Elham, Y (reprint author), Tehran University of Medical Sciences, Faculty of Dentistry, Dental Research Center, Dentistry Research Institute, Department of Oral Medicine, Tehran, Iran.
EM y-elham@razi.tums.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 615
EP 625
DI 10.1007/s12253-019-00646-9
PG 11
ER
PT J
AU Singh, G
Mishra, S
Chander, H
AF Singh, Garima
Mishra, Sarthak
Chander, Harish
TI KIBRA Team Up with Partners to Promote Breast Cancer Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast Cancer; Metastasis; Kibra; DDR1; DLC1&PKCζ
ID Breast Cancer; Metastasis; Kibra; DDR1; DLC1&PKCζ
AB Among women, breast cancer is the most frequently diagnosed cancer. Most of the breast cancers represent metastasis to distant organs at the time of diagnosis and accounts for the majority of deaths. Metastasis is characterized by many genetic aberrations including mutations, overexpression of oncogenes etc. KIBRA (KIdney/BRAin protein), a scaffolding protein is recently described as an important player in the process of invasion and metastasis. The Kidney/BRAin protein through its different domains interacts with various proteins to couple cytoskeleton arrangement, cell polarity and migration. N terminal and C terminal of the protein contains the WW, Internal C2 & putative class III PDZ domain that interacts with DDR1, DLC1 & PKCζ. These protein-protein interactions equip the breast cancer cells to invade and metastasize. Here, we discuss a comprehensive knowledge about the KIBRA protein, its domains and the interacting partners involved in metastasis of breast cancer.
C1 [Singh, Garima] Central University of Punjab, Department of Human Genetics and Molecular Medicine, Laboratory of Molecular Medicine, 151001 Bathinda, India.
[Mishra, Sarthak] Central University of Punjab, Department of Human Genetics and Molecular Medicine, Laboratory of Molecular Medicine, 151001 Bathinda, India.
[Chander, Harish] Central University of Punjab, Department of Human Genetics and Molecular Medicine, Laboratory of Molecular Medicine, 151001 Bathinda, India.
RP Chander, H (reprint author), Central University of Punjab, Department of Human Genetics and Molecular Medicine, Laboratory of Molecular Medicine, 151001 Bathinda, India.
EM harish.chander@cup.edu.in
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 627
EP 634
DI 10.1007/s12253-019-00660-x
PG 8
ER
PT J
AU Assumpcao, P
Khayat, A
Araujo, T
Barra, W
Ishak, G
Cruz, A
Santos, S
Santos,
Demachki, S
Assumpcao, P
Calcagno, D
Santos, N
Assumpcao, M
Moreira, F
Santos, A
Assumpcao, C
Riggins, G
Burbano, R
AF Assumpcao, Paulo
Khayat, Andre
Araujo, Taissa
Barra, Williams
Ishak, Geraldo
Cruz, Aline
Santos, Sidney
Santos, Andrea
Demachki, Samia
Assumpcao, Paula
Calcagno, Danielle
Santos, Ney
Assumpcao, Monica
Moreira, Fabiano
Santos, Andre
Assumpcao, Carolina
Riggins, Gregory
Burbano, Rommel
TI The Small Bowel Cancer Incidence Enigma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Small bowel cancer; Low incidence; DNA repair; Enigma
ID Small bowel cancer; Low incidence; DNA repair; Enigma
AB Although the small bowel is a vast organ with a highly proliferative epithelium, the incidence of small bowel cancers is surprisingly low. Many factors could be involved in this unexpected cancer incidence, including difficult access to the exploration of the small bowel mucosa, which might lead to missed diagnoses of non-obstructive and non-bleeding small tumours. Moreover, possible factors that influence the low incidence include more efficient machinery of DNA replication and DNA repair enzymes, peculiarities in microbiota components, competence of the immune system, and the speed of intestinal transit. Importantly, the answer for the enigmatic risk of driver mutations caused by replication errors may be hidden in the small bowel, which is an obscure part of digestive tract that is usually inaccessible by endoscopic or colonoscopic conventional investigations. These observations warrant the necessity of an urgent exploration of small bowel features, including the evaluation of DNA replication controls and expression of DNA repair genes, in order to shed light on these obscure events.
C1 [Assumpcao, Paulo] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Khayat, Andre] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Araujo, Taissa] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Barra, Williams] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Ishak, Geraldo] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Cruz, Aline] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Santos, Sidney] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Santos, Andrea] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Demachki, Samia] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Assumpcao, Paula] Universidade Federal do Para, Programa de Pos-Graduacao em Genetica e Biologia Molecular, 66075-110 Belem, Brazil.
[Calcagno, Danielle] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Santos, Ney] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Assumpcao, Monica] Hospital Universitario Joao de Barros Barreto, Servico de Endoscopia Digestiva, 66073-000 Belem, Brazil.
[Moreira, Fabiano] Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
[Santos, Andre] Universidade Federal do Para, Programa de Pos-Graduacao em Genetica e Biologia Molecular, 66075-110 Belem, Brazil.
[Assumpcao, Carolina] Hospital Alemao Oswaldo Cruz, Servico de Cirurgia Oncologica, 01327-001 Sao Paulo, Brazil.
[Riggins, Gregory] Johns Hopkins Hospital, Department of Neurosurgery, 21287 Baltimore, MD, USA.
[Burbano, Rommel] Hospital Ophir Loyola, Laboratorio de Biologia Molecular, 66060-281 Belem, Brazil.
RP Assumpcao, P (reprint author), Universidade Federal do Para, Nucleo de Pesquisas em Oncologia, 66073-000 Belem, Brazil.
EM assumpcaopp@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 635
EP 639
DI 10.1007/s12253-019-00682-5
PG 5
ER
PT J
AU Zalatnai, A
Kis-Orha, V
AF Zalatnai, Attila
Kis-Orha, Viktoria
TI Solid-pseudopapillary Neoplasms of the Pancreas is still an Enigma: a Clinicopathological Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Pancreas; Solid-pseudopapillary neoplasm; Histogenesis; Review
ID Pancreas; Solid-pseudopapillary neoplasm; Histogenesis; Review
AB The solid-pseudopapillary neoplasm of the pancreas is a rare but enigmatic entity occurring mainly in young women. Since the first description by V. Frantz in 1959 the terminology of this tumor has continuously changed but it has remained simply descriptive, because the exact histogenesis is still obscure. Although in majority of cases the survival is excellent, nevertheless, the expected prognosis is not exactly predictable. In this review the authors aim to summarize its clinicopathological features, the expected biological behavior, the molecular alterations, the immune phenotype and discuss the putative histogenesis. From diagnostic point of view, the salient histological characteristic findings are analyzed that would help to differentiate it from other, look-alike pancreatic tumors, and suggestions are made about the desirable content of the histological report.
C1 [Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Kis-Orha, Viktoria] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM zalatnai@korb1.sote.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 641
EP 649
DI 10.1007/s12253-019-00671-8
PG 9
ER
PT J
AU Ding, L
Lu, Sh
Li, Y
AF Ding, Lei
Lu, Shengdi
Li, Yanli
TI Regulation of PD-1/PD-L1 Pathway in Cancer by Noncoding RNAs
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE PD-1/PD-L1 pathway; Immune checkpoint blockade; Noncoding RNA; microRNA
ID PD-1/PD-L1 pathway; Immune checkpoint blockade; Noncoding RNA; microRNA
AB Immune checkpoint blockade has demonstrated significant anti-tumor immunity in an array of cancer types, yet the underlying regulatory mechanism of it is still obscure, and many problems remain to be solved. As an inhibitory costimulatory signal of T-cells, the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway can paralyze T-cells at the tumor site, enabling the immune escape of tumor cells. Although many antibodies targeting PD-1/PD-L1 have been developed to block their interaction for the treatment of cancer, the reduced response rate and resistance to the therapies call for further comprehension of this pathway in the tumor microenvironment. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main types of noncoding RNAs that play critical parts in the regulation of immune response in tumorigenesis, including the PD-1/ PD-L1 pathway. Here we summarize the most recent studies on the control of this pathway by noncoding RNAs in cancer and hopefully will offer new insights into immune checkpoint blockade therapies.
C1 [Ding, Lei] Shanghai University, School of Life Science, Lab for Noncoding RNA & Cancer, 200444 Shanghai, China.
[Lu, Shengdi] Shanghai Jiaotong University, Shanghai Sixth People’s Hospital, 200233 Shanghai, China.
[Li, Yanli] Shanghai University, School of Life Science, Lab for Noncoding RNA & Cancer, 200444 Shanghai, China.
RP Li, Y (reprint author), Shanghai University, School of Life Science, Lab for Noncoding RNA & Cancer, 200444 Shanghai, China.
EM liyanli@shu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 651
EP 663
DI 10.1007/s12253-019-00735-9
PG 13
ER
PT J
AU Cserni, G
Sejben, A
AF Cserni, Gabor
Sejben, Anita
TI Grading Ductal Carcinoma In Situ (DCIS) of the Breast – What’s Wrong with It?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Breast cancer; Ductal carcinoma in situ; Grade
ID Breast cancer; Ductal carcinoma in situ; Grade
AB Ductal carcinoma in situ of the breast is a non-obligate precursor of invasive breast cancer, and at its lower risk endmight not need treatment, a hypothesis tested in several currently running randomized clinical trials. This review describes the heterogeneity of grading ductal carcinoma in situ (DCIS). First it considers differences between low and high grade DCIS, and then it looks at several grading schemes and highlights how different these are, not only in the features considered for defining a given grade but also in their wording of a given variable seen in the grade in question. Rather than being fully comprehensive, the review aims to illustrate the inconsistencies. Reproducibility studies on grading mostly suggestive of moderate agreement on DCIS differentiation are also illustrated. The need for a well structured, more uniformand widely accepted language for grading DCIS is urged to avoid misunderstanding based misclassifications and improper treatment selection.
C1 [Cserni, Gabor] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Sejben, Anita] University of Szeged, Department of Pathology, Allomas u. 1, H-6725 Szeged, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
EM cserni@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 665
EP 671
DI 10.1007/s12253-019-00760-8
PG 7
ER
PT J
AU Burian, Zs
Ladanyi, A
Barbai, T
Piurko, V
Garay, T
Raso, E
Timar, J
AF Burian, Zsuzsanna
Ladanyi, Andrea
Barbai, Tamas
Piurko, Violetta
Garay, Tamas
Raso, Erzsebet
Timar, Jozsef
TI Selective Inhibition of HIF1α Expression by ZnSO4 Has Antitumoral Effects in Human Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ZnSO4; Human melanoma; HIF1α; Metastasis inhibition
ID ZnSO4; Human melanoma; HIF1α; Metastasis inhibition
AB Zinc as an essential trace metal is a ubiquitous component of various molecules of the cell. Studies indicated that it may modulate functions of various cancer cell types, and can even inhibit metastasis formation in experimental models. In melanoma, zinc was shown to affect melanin production and to induce apoptosis. Using human melanoma cell lines, we have tested the effects of ZnSO4 on cell proliferation, survival, migration as well as in vivo on experimental liver colony formation. We have found that ZnSO4 has antiproliferative and proapoptotic effects in vitro. In SCID mice intraperitoneal administration of ZnSO4 specifically inhibited liver colony formation without affecting primary tumor growth. To reveal the molecular mechanisms of action of zinc in human melanoma, we have tested mRNA expression of zinc finger transcription factors and found a strong inhibitory effect on HIF1α, as compared to WT1 whereas HIF2α and MTF1 expression was unaffected. Immunohistochemical detection of HIF1α protein in liver metastases confirmed its decreased nuclear expression after in vivo ZnSO4 treatment. These data indicate that in human melanoma zinc administration may have an antimetastatic effect due to a selective downregulation of HIF1α.
C1 [Burian, Zsuzsanna] National Institute of OncologyBudapest, Hungary.
[Ladanyi, Andrea] National Institute of OncologyBudapest, Hungary.
[Barbai, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Piurko, Violetta] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Garay, Tamas] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM jtimar@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 673
EP 679
DI 10.1007/s12253-018-00573-1
PG 7
ER
PT J
AU Nariman-Saleh-Fam, Z
Saadatian, Z
Nariman-Saleh-Fam, L
Ouladsahebmadarek, E
Tavakkoly-Bazzaz, J
Bastami, M
AF Nariman-Saleh-Fam, Ziba
Saadatian, Zahra
Nariman-Saleh-Fam, Lida
Ouladsahebmadarek, Elaheh
Tavakkoly-Bazzaz, Javad
Bastami, Milad
TI An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1 rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; Polymorphism; Iran; GWAS; Association; Meta-analysis
ID Esophageal cancer; Polymorphism; Iran; GWAS; Association; Meta-analysis
AB One of the highest risk of esophageal squamous cell carcinoma (ESCC) in the world has been reported in Iran, which is located in the Asian esophageal cancer belt. ESCC constitutes 90% of the esophageal cancer cases in Iran. Genome wide association studies (GWASs) in Chinese have identified a number of candidate variants, of which PLCE1rs2274223, C20orf54rs13042395 and RUNX1rs2014300 are studied in high risk populations including Chinese, Caucasians and Africans. However, results are inconsistent and it is unknown whether similar associations exist in Iranian population. We evaluated association of three GWAS identified variants with risk of ESCC in an Iranian cohort consisted of 200 ESCC patients and 300 healthy controls and conducted meta-analysis of ESCC risk associated with rs2274223 (involving 9810 cases and 13,128 controls) and rs13042395 (involving 2363 cases and 5329 controls). Logistic regression analysis showed that rs2274223 was associated with ESCC under codominant [GG/AA, 2.47(1.17–5.23), P:0.021], dominant [AG+GG/AA, 1.57(1.09–2.27), P:0.016], recessive [GG/AA+AG, 2.18(1.04–4.56), P:0.036] and log-additive models [1.51(1.12–2.02), P:0.006]. C20orf54 rs13042395 was not associated with ESCC under any genetic model. RUNX1 rs2014300 was associated with risk of ESCC assuming codominant [AG/GG, 0.63(0.41–0.97), P:0.018], dominant [AG+ AA/GG, 0.59 (0.39–0.89), P:0.010] and log-additive models [0.61 (0.42–0.87), P: 0.005]. Meta-analysis found significant associations between rs2274223 and ESCC under all analyzed genetic models. However, meta-analysis stratified by ethnicity showed a significant association in Asians but not non-Asian populations. No significant association was found for rs13042395 in meta-analysis. This study provided first evidence for association of GWAS-identified variants with risk of ESCC in an Iranian cohort.
C1 [Nariman-Saleh-Fam, Ziba] Tabriz University of Medical Sciences, Women’s Reproductive Health Research CenterTabriz, Iran.
[Saadatian, Zahra] Shahid Beheshti University of Medical Sciences, Faculty of Medicine, Student Research CommitteeTehran, Iran.
[Nariman-Saleh-Fam, Lida] Tabriz University of Medical Sciences, Liver and Gastrointestinal Diseases Research CenterTabriz, Iran.
[Ouladsahebmadarek, Elaheh] Tabriz University of Medical Sciences, Women’s Reproductive Health Research CenterTabriz, Iran.
[Tavakkoly-Bazzaz, Javad] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Bastami, Milad] Tabriz University of Medical Sciences, Immunology Research CenterTabriz, Iran.
RP Tavakkoly-Bazzaz, J (reprint author), Shahid Beheshti University of Medical Sciences, Department of Medical Genetics, Tehran, Iran.
EM tavakkolybazzazj@tums.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 681
EP 692
DI 10.1007/s12253-019-00579-3
PG 12
ER
PT J
AU Zhang, J
Zhang, J
Chen, W
Li, H
Li, M
Li, L
AF Zhang, Jianguo
Zhang, Jianzhong
Chen, Wenqi
Li, Huiyu
Li, Meiying
Li, Lisha
TI Bioinformatics Analysis Makes Revelation to Potential Properties on Regulation and Functions of Human Sox2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bioinformatics analysis; SOX2; Protein-protein interactions; Proteomics; Protein regulation
ID Bioinformatics analysis; SOX2; Protein-protein interactions; Proteomics; Protein regulation
AB Sex determining region Y-box 2 (Sox2) is a transcription factor that is essential for maintaining self-renewal or pluripotency of undifferentiated embryonic stem cells. The expression and distribution of Sox2 in tumor tissues have been extensively recorded, which are related to the progression and metastasis of tumor. However, a complete mechanistic understanding of Sox2 regulation and function remains to be studied. Herein, we show new potential properties of Sox2 regulation and functions from bioinformatics analysis. We use numerous algorithms to characterize the Sox2 gene promoter elements and the Sox2 protein structure, physio-chemical, localization properties and its evolutionary relationships. The expression of Sox2 is regulated by a diverse set of transcription factors and associated with the levels of methylation of CpG Islands in promoters. The structural properties of Sox2 indicate that Sox2 expresses as a stem cell marker in a variety of stem cells. Sox2 together with other transcription factors or proteins regulate the expression of downstream target genes, which makes a great difference to the biological function of stem cells. Not only stem cells, Sox2 also play an important role in tumor cells. In conclusion, this information from bioinformatics analysis will help to understand Sox2 regulation and functions better in future attempts.
C1 [Zhang, Jianguo] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of PathobiologyChangchun, China.
[Zhang, Jianzhong] Qingdao University, Department of MedicineQingdao, China.
[Chen, Wenqi] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of PathobiologyChangchun, China.
[Li, Huiyu] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of PathobiologyChangchun, China.
[Li, Meiying] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of PathobiologyChangchun, China.
[Li, Lisha] Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of PathobiologyChangchun, China.
RP Li, L (reprint author), Jilin University, Ministry of Education, Norman Bethune Medical College, The Key Laboratory of Pathobiology, Changchun, China.
EM lilisha@jlu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 693
EP 706
DI 10.1007/s12253-019-00581-9
PG 14
ER
PT J
AU Li, X
Xu, X
Chen, K
Wu, H
Wang, Y
Yang, Sh
Wang, K
AF Li, Xinwei
Xu, Xueying
Chen, Keng
Wu, Haijian
Wang, Yirong
Yang, Shuxu
Wang, Kun
TI miR-370 Sensitizes TMZ Response Dependent of MGMT Status in Primary Central Nervous System Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Primary central nervous system lymphoma; miR-370; MGMT; Temozolomide; Drug resistance
ID Primary central nervous system lymphoma; miR-370; MGMT; Temozolomide; Drug resistance
AB Primary central nervous system lymphoma (PCNSL) is an aggressive and rare subtype of non-Hodgkin lymphoma, arising exclusively in the CNS with a poor prognosis. Previous evidence has proved that MGMT was a promising target involving in TMZ resistance of PCNSL. Our study described a new miR-370-mediated mechanism of MGMT regulation in PCNSL. We first showed that miR-370 was downregulated in PCNSL tissues, while MGMT was inversely overexpressed. It was also observed that miR-370 suppressed the expression of MGMT. Additionally, upregulation of miR-370 significantly increased TMZ sensitivity dependent of MGMT, thus suppressed Raji cell proliferation and induced apoptosis in vitro. In conclusion, these results suggest that miR-370 is a potential target in PCNSL treatment.
C1 [Li, Xinwei] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Xu, Xueying] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Chen, Keng] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Wu, Haijian] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Wang, Yirong] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Yang, Shuxu] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
[Wang, Kun] Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
RP Wang, K (reprint author), Zhejiang University, Medical College, Sir Run Run Shaw Hospital, Department of Neurosurgery, 310016 Hangzhou, China.
EM simonkunwang@zju.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 707
EP 714
DI 10.1007/s12253-019-00605-4
PG 8
ER
PT J
AU Mehemmai, Ch
Cherbal, F
Hamdi, Y
Guedioura, A
Benbrahim, W
Bakour, R
Abdelhak, S
AF Mehemmai, Chiraz
Cherbal, Farid
Hamdi, Yosr
Guedioura, Abdelmoumene
Benbrahim, Wassila
Bakour, Rabah
Abdelhak, Sonia
TI BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Algerian women; Aures region; HBOC; BRCA1; BRCA2; Genetic testing; NGS; Cancer panel
ID Algerian women; Aures region; HBOC; BRCA1; BRCA2; Genetic testing; NGS; Cancer panel
AB Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. In this study, we aimed to investigate the mutation spectrum of BRCA1 and BRCA2 genes in hereditary breast/ovarian cancer (HBOC) families from the Aures region (eastern Algeria). High risk breast/ovarian cancer families were selected from overall 1162 consecutive patients collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Recurrent mutations on BRCA1 and BRCA2 previously found in Algerian patients were screened using PCR-direct sequencing in 113 HBOC families. In addition, for the first time in Algeria, HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Six distinct deleterious mutations in BRCA1 and BRCA2 and a new VUS in PALB2 were detected in ten patients. Two distinct BRCA2 pathogenic variants c.1813dupA and c.8485C > T detected in two young female triple negative breast cancer (TNBC) patients, respectively, with a family history of male breast cancer, are reported here for the first time in Algerian population. Interestingly, we also detected a BRCA exon 15 deletion in two unrelated young female TNBC patients with strong family history of breast/ovarian cancer. Our study showed differences in the distribution of the mutation spectrum of BRCA genes between the Aures region and the north central region of Algeria. Our results will contribute in the implementation of genetic counseling and testing for patients and families at risk of hereditary breast and ovarian cancer.
C1 [Mehemmai, Chiraz] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Cherbal, Farid] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Hamdi, Yosr] University of Tunis El Manar, Institut Pasteur de Tunis, Laboratory of Biomedical Genomics and Oncogenetics (LRTI, IPT 05)Tunis, Tunisia.
[Guedioura, Abdelmoumene] USTHB, Faculty of Biological Sciences, LOBEMAlgiers, Algeria.
[Benbrahim, Wassila] Anti-cancer center of BatnaBatna, Algeria.
[Bakour, Rabah] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Abdelhak, Sonia] University of Tunis El Manar, Institut Pasteur de Tunis, Laboratory of Biomedical Genomics and Oncogenetics (LRTI, IPT 05)Tunis, Tunisia.
RP Cherbal, F (reprint author), USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, 16111 Algiers, Algeria.
EM farid.cherbal@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 715
EP 726
DI 10.1007/s12253-019-00586-4
PG 12
ER
PT J
AU Mervai, Zs
Reszegi, A
Miklya, I
Knoll, J
Schaff, Zs
Kovalszky, I
Baghy, K
AF Mervai, Zsolt
Reszegi, Andrea
Miklya, Ildiko
Knoll, Jozsef
Schaff, Zsuzsa
Kovalszky, Ilona
Baghy, Kornelia
TI Inhibitory Effect of (2R)-1-(1-Benzofuran-2-yl)-N-propylpentan-2-amine on Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BPAP; Lung adenocarcinoma; Cancer; Tumor inhibition; FVB/N; Geroconversion
ID BPAP; Lung adenocarcinoma; Cancer; Tumor inhibition; FVB/N; Geroconversion
AB BPAP is a potent enhancer substance with catecholaminergic and serotoninergic activity in the brain. It was discovered that it is also effective against certain types of experimental cancers, showing the most promising results in case of lung cancer. That is why we tested its efficacy in two different doses in a newly developed EGFR wild type mouse lung adenocarcinoma xenograft model. Experiments were conducted on FVB/N and SCID mouse strains treated with low and high dose of BPAP. Body weight, survival, and tumor volumes were recorded. Furthermore, the activity of major signaling pathways of NSCLC such as MAPK and Akt/mTOR as well as cell cycle regulation were determined. Significant inhibition of tumor growth was exerted by both doses, but the mechanism of action was different. High dose directly inhibited, whereas low dose activated the main signaling pathways. Exposure to low dose BPAP resulted in elevated activity of the mTOR pathway together with p16INK-induced cell cycle arrest, a typical feature of geroconversion, a senescent state characterized by loss of cell proliferation. Finally the events culminated in cell cycle inhibition point in case of both doses mirrored by the decrease of cyclin D1, CDK4 and PCNA. In addition, BPAP treatment had a beneficial effect on bodyweight suggesting that the compound at least in part is able to compensate the cancer-related wasting. In view of the low toxicity and confirmed antitumor effect of BPAP against experimental lung adenocarcinoma, this novel compound deserves further attention.
C1 [Mervai, Zsolt] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Reszegi, Andrea] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Miklya, Ildiko] Semmelweis University, Department of Pharmacology and PharmacotherapyBudapest, Hungary.
[Knoll, Jozsef] Semmelweis University, Department of Pharmacology and PharmacotherapyBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Baghy, K (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM baghy.kornelia@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 727
EP 734
DI 10.1007/s12253-019-00603-6
PG 8
ER
PT J
AU Naruse, T
Yanamoto, S
Okuyama, K
Ohmori, K
Tsuchihashi, H
Furukawa, K
Yamada, Shi
Umeda, M
AF Naruse, Tomofumi
Yanamoto, Souichi
Okuyama, Kohei
Ohmori, Keisuke
Tsuchihashi, Hiroki
Furukawa, Kohei
Yamada, Shin-ichi
Umeda, Masahiro
TI Immunohistochemical Study of PD-1/PD-L1 Axis Expression in Oral Tongue Squamous Cell Carcinomas: Effect of Neoadjuvant Chemotherapy on Local Recurrence
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PD-1; PD-L1; Local recurrence; NAC
ID PD-1; PD-L1; Local recurrence; NAC
AB While neoadjuvant chemotherapy (NAC) for patients with oral tongue squamous cell carcinoma (OTSCC) may improve tumor microenvironment, it may lead to local immune suppression caused by residual cancer cells. The efficacy of NAC is therefore controversial. In our study, we investigated tumor microenvironments after NAC using immune checkpoint molecules, and evaluated the association between tumor microenvironments, clinicopathological factors and outcomes. We reviewed the records of 121 patients who underwent radical surgery for OTSCC between April 2001 and March 2015. Patients with a positive surgical margin and a follow up period of less than 6 months were excluded. For these patients, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) expressions were immunohistochemically examined. The expression of PD-1 and PD-L1 were significantly associated with local recurrence in patients with OTSCC (P < 0.01 and P < 0.01, respectively). We found a significant decrease in 5-year disease specific survival rate for patients with combined PD-1+/PD-L1+ expressions (P < 0.05). In the subgroup analysis of local recurrence between the NAC treated group and those who received surgery alone, high levels of PD-1 and PD-L1 expressions were significantly found in the former, but not in the latter group. Local recurrence in the NAC treated group may contribute to local immune suppression in OTSCC. NAC lead to local immune suppression and immune checkpoint molecules play an important role in local recurrence in patients with OTSCC who received NAC. NAC modality can’t be recommended for patients with OTSCC at present.
C1 [Naruse, Tomofumi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yanamoto, Souichi] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Okuyama, Kohei] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Ohmori, Keisuke] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Tsuchihashi, Hiroki] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Furukawa, Kohei] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
[Yamada, Shin-ichi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 390-8621 Matsumoto, Nagano, Japan.
[Umeda, Masahiro] Nagasaki University, Graduate School of Biomedical Sciences, Department of Clinical Oral Oncology, 1-7-1 Sakamoto, 852-8588 Nagasaki, Japan.
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EM naruse12@nagasaki-u.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 735
EP 742
DI 10.1007/s12253-019-00606-3
PG 8
ER
PT J
AU Vukovic, V
Karan-Djurasevic, T
Antic, D
Tosic, N
Kostic, T
Marjanovic, I
Dencic-Fekete, M
Djurasinovic, V
Pavlovic, S
Mihaljevic, B
AF Vukovic, Vojin
Karan-Djurasevic, Teodora
Antic, Darko
Tosic, Natasa
Kostic, Tatjana
Marjanovic, Irena
Dencic-Fekete, Marija
Djurasinovic, Vladislava
Pavlovic, Sonja
Mihaljevic, Biljana
TI Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chronic lymphocytic leukemia; Fludarabine; Cyclophosphamide; SLC28A3 expression; CYP2B6*6 allele; Response to therapy
ID Chronic lymphocytic leukemia; Fludarabine; Cyclophosphamide; SLC28A3 expression; CYP2B6*6 allele; Response to therapy
AB Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients.
C1 [Vukovic, Vojin] Clinical Center of Serbia, Clinic for HematologyBelgrade, Serbia.
[Karan-Djurasevic, Teodora] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Antic, Darko] Clinical Center of Serbia, Clinic for HematologyBelgrade, Serbia.
[Tosic, Natasa] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Kostic, Tatjana] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Marjanovic, Irena] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Dencic-Fekete, Marija] University of Belgrade, Faculty of Medicine, Institute for PathologyBelgrade, Serbia.
[Djurasinovic, Vladislava] Clinical Center of Serbia, Clinic for HematologyBelgrade, Serbia.
[Pavlovic, Sonja] University of Belgrade, Institute of Molecular Genetics and Genetic EngineeringBelgrade, Serbia.
[Mihaljevic, Biljana] Clinical Center of Serbia, Clinic for HematologyBelgrade, Serbia.
RP Vukovic, V (reprint author), Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia.
EM vojinvukovic@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 743
EP 752
DI 10.1007/s12253-019-00613-4
PG 10
ER
PT J
AU Jia, Y
Tian, Y
An, Sh
Yang, D
AF Jia, Ying
Tian, Ye
An, Shuo
Yang, Dong
TI Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNA-195; Glioma; Prognosis; Cell cycle; Cell proliferation; Apoptosis
ID microRNA-195; Glioma; Prognosis; Cell cycle; Cell proliferation; Apoptosis
AB Glioma is the most common and aggressive intracranial malignant tumor with poor prognosis. Acts as a tumor suppressor, microRNA-195 (miR-195) plays important roles in a variety of cancers. However, the expression of miR-195 and role of miR- 195 in glioma are still not well understood. 186 patients with glioma were enrolled and the follow-up period ranges from 1 to 69months. MiR-195 was exogenously transfected into human glioma U87 cell line. The cell proliferation assay (CCK-8), colony formation assay, cell cycle analysis and cell apoptosis analysis were examined to investigate miR-195 effect on U87 cells. MiR- 195 levels were reversely correlated with pathological grades (r = −0.487, p = 0.003). For patients with low miR-195 levels, their median survival time was 15 months, whereas the median survival time in patients with high miR-195 levels was 56.53 months. Multi-factor Cox regression analysis showed that high level of miR-195 (Odds ratio (OR): 0.347, 95% CI: 0.121–0.992) was associated with decreased mortality risk of patients. Moreover, overexpression of miR-195 inhibits proliferation and colony formation, and induces apoptosis of U87 cells. MiR-195 could block the glioma cells in G0/G1 phase, reducing S phase cells and regulating apoptosis related proteins (Caspase-3, Caspase-8, Caspase-9 and Bcl-2). Downregulation of miR-195 was associated with poor prognosis in human glioma. MiR-195 acted as tumor suppressor through inhibiting cell proliferation and promoting cell apoptosis via blockade of cell cycle and regulation of apoptosis related proteins.
C1 [Jia, Ying] Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
[Tian, Ye] Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
[An, Shuo] Tianjin Medical University General Hospital, Department of Neurosurgery, 300052 Tianjin, China.
[Yang, Dong] Tianjin Medical University General Hospital, Department of Otorhinolaryngology, No.154 An Shan Dao, Heping District, 300052 Tianjin, China.
RP Yang, D (reprint author), Tianjin Medical University General Hospital, Department of Otorhinolaryngology, 300052 Tianjin, China.
EM yangdong_dr@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 753
EP 763
DI 10.1007/s12253-019-00622-3
PG 11
ER
PT J
AU Wang, Q
Li, Ch
Xie, Z
Bu, Z
Shi, L
Wang, Ch
Jiang, F
AF Wang, Qianru
Li, Chunjiao
Xie, Zhongli
Bu, Zhiguo
Shi, Liwei
Wang, Chuan
Jiang, Feng
TI The Development and Application of Virtual Reality Animation Simulation Technology: Take Gastroscopy Simulation System as an Example
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VR animation; Medical simulation; Gastroscopy simulation; Operating system; Cross-border fusion
ID VR animation; Medical simulation; Gastroscopy simulation; Operating system; Cross-border fusion
AB Virtual reality (VR) technology has a great potential in the field of medical simulation due to its immersion, interactivity and autonomy. It provides a new direction for integration and application in various disciplines. Combination of VR technology and clinical practice brings great convenience for medical education and experiments. Modern VR simulators can create realistic environments that capture minute anatomical details with high accuracy and solves the problem of difficulty in mass productions with traditional devices. Taking gastroscopy simulation system as an example, this paper discusses the development and application of VR animation technology, together with its excellent performance and current research status in surgery, scientific research, training and education.
C1 [Wang, Qianru] Film-Video-Animation School, Sichuan Fine Arts Institute, 401331 Chongqing, China.
[Li, Chunjiao] Film-Video-Animation School, Sichuan Fine Arts Institute, 401331 Chongqing, China.
[Xie, Zhongli] Film-Video-Animation School, Sichuan Fine Arts Institute, 401331 Chongqing, China.
[Bu, Zhiguo] Film-Video-Animation School, Sichuan Fine Arts Institute, 401331 Chongqing, China.
[Shi, Liwei] Chongqing General Hospital, Digestive Department, No. 104, Pipashan Main Street, Yuzhong District, 400014 Chongqing, China.
[Wang, Chuan] Chongqing General Hospital, Digestive Department, No. 104, Pipashan Main Street, Yuzhong District, 400014 Chongqing, China.
[Jiang, Feng] Chongqing General Hospital, Digestive Department, No. 104, Pipashan Main Street, Yuzhong District, 400014 Chongqing, China.
RP Jiang, F (reprint author), Chongqing General Hospital, Digestive Department, 400014 Chongqing, China.
EM FengJiang17@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 765
EP 769
DI 10.1007/s12253-019-00590-8
PG 5
ER
PT J
AU Zhu, W
Ji, X
AF Zhu, Wei
Ji, Xiaoliang
TI The Impact of MicroRNA-133a on Prognosis and Clinicopathological Parameters for Digestive System Cancers: a Comprehensive Study Based on Meta-Analysis and TCGA Database
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNA-133a; Digestive system Cancer; TCGA; Meta-analysis
ID MicroRNA-133a; Digestive system Cancer; TCGA; Meta-analysis
AB We conducted a meta-analysis on the impact of microRNA-133a (miR-133a) on digestive system cancers, and verified the results through The Cancer Genome Atlas (TCGA). Relevant studies were searched in English and Chinese database and meta-analysis was performed using Stata 12.0. The corresponding information of miR-133a and digestive system cancers were obtained from TCGA database and analysis was performed using SPSS. Increased miR-133a expression was linked with favorable overall survival (OS) in digestive system cancers (HR = 0.539, 95% CI: 0.416–0.698, P < 0.001), digestive tract cancers (HR =0.558, 95% CI: 0.406–0.767, P < 0.001), esophageal squamous cell carcinoma (ESCC) (HR = 0.427, 95% CI: 0.265–0.690, P = 0.001) and gastric cancer (HR = 0.541, 95%CI: 0.385–0.761, P < 0.001). The expression ofmiR-133a was significantly lower in cancer tissue compared with adjacent tissue for ESCC (P < 0.001), gastric cancer (P < 0.001), colorectal cancer (P < 0.001) and hepatocellular carcinoma (P = 0.002). Meanwhile, the area under the ROC curve (AUC) value for miR-133a was 0.836, 0.888, and 0.99 in ESCC, gastric cancer and colorectal cancer. MiR-133a is a tumor suppressor with prognostic and diagnostic values for digestive system cancers. High miR-133a expression was associated with better prognosis and less adverse clinicopathological parameters. More research should be performed to test these findings.
C1 [Zhu, Wei] The First Hospital of Huzhou, Department of General SurgeryHuzhou, Zhejiang, China.
[Ji, Xiaoliang] Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine, Department of General SurgeryHuzhou, Zhejiang, China.
RP Ji, X (reprint author), Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine, Department of General Surgery, Huzhou, China.
EM jixiaolianghz@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 771
EP 781
DI 10.1007/s12253-019-00619-y
PG 11
ER
PT J
AU Miyamoto, M
Takano, M
Tsuda, H
Matsuura, H
Sakamoto, T
Takasaki, K
Kato, K
Soyama, H
Aoyama, T
Ishibashi, H
Iwahashi, H
Furuya, K
AF Miyamoto, Morikazu
Takano, Masashi
Tsuda, Hitoshi
Matsuura, Hiroko
Sakamoto, Takahiro
Takasaki, Kazuki
Kato, Kento
Soyama, Hiroaki
Aoyama, Tadashi
Ishibashi, Hiroki
Iwahashi, Hideki
Furuya, Kenichi
TI The Haphazard Pattern in Grade-3 Endometrioid Carcinoma Is Associated with Poor Prognosis and Tumor Lymphocyte Infiltration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial carcinoma; Endometrial endometrioid carcinoma; Invasive pattern; Tumor infiltrating lymphocyte
ID Endometrial carcinoma; Endometrial endometrioid carcinoma; Invasive pattern; Tumor infiltrating lymphocyte
AB The aim of this study was to examine the associations among the haphazard invasive patterns, defined as directionless infiltration into the myometrium; expression of key proteins; tumor infiltrative lymphocytes (TILs); and the prognosis of gade-3 endometrioid carcinoma (G3EC). Between 1990 and 2013, patients with G3EC who underwent surgery at our hospital were identified. Invasive patterns were classified into either haphazard, infiltrative, or expansile patterns. The estrogen, progesterone, androgen receptor, cytokeratin 5/6, epidermal growth factor receptor, E-cadherin, snail-2, vimentin, ZEB1, chromogranin A, synaptophysin, MLH1, MSH2, MSH6, and PMS2 levels were evaluated by immunochemical analysis. The degree of strong or weak lymphocyte infiltration (LI) were evaluated using zone formation of LI at the invasive front. Haphazard, infiltrative, and expansile patterns were discovered in 8 (18%), 6 (13%), and 31 (69%) cases, respectively. Cases with the haphazard patterns were diagnosed at a more advanced stage (p < 0.01) and recurred more frequently (p < 0.01). There were statistical differences in progression-free survival (PFS) and overall survival (OS) between the three groups (PFS; p < 0.01: OS; p < 0.01). In multivariate analysis, only the haphazard pattern was found to be an independent, worse prognostic factor of PFS (Hazard ratio (HR) =10.8, p < 0.01) and OS (HR= 23.3, p < 0.01). Furthermore, the haphazard invasive pattern was related with weak LI (p < 0.01) but not with the expression of all proteins analyzed. The haphazard pattern was found to be a worse prognostic factor and was associated with weak LI in G3EC. The aggressive feature of G3EC might be associated with LI but not tumor biology.
C1 [Miyamoto, Morikazu] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Takano, Masashi] National Defense Medical College, Department of Clinical OncologyTokorozawa, Saitama, Japan.
[Tsuda, Hitoshi] National Defense Medical College, Department of Basic PathologyTokorozawa, Saitama, Japan.
[Matsuura, Hiroko] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Sakamoto, Takahiro] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Takasaki, Kazuki] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Kato, Kento] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Soyama, Hiroaki] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Aoyama, Tadashi] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Ishibashi, Hiroki] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Iwahashi, Hideki] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Furuya, Kenichi] National Defense Medical College, Department of Obstetrics and Gynecology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
RP Miyamoto, M (reprint author), National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Japan.
EM morikazu1118@hotmail.co.jp
CR Prat J, 2015, Pathology of cancers of the female genital tract. Int J Gynaecol Obstet 131(Suppl 2):S132–S145. , DOI 10. 1016/j.ijgo.2015.06.010.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 783
EP 790
DI 10.1007/s12253-019-00624-1
PG 8
ER
PT J
AU Lubowicka, E
Zbucka-Kretowska, M
Sidorkiewicz, I
Zajkowska, M
Gacuta, E
Puchnarewicz, A
Chrostek, L
Szmitkowski, M
Lawicki, S
AF Lubowicka, Emilia
Zbucka-Kretowska, Monika
Sidorkiewicz, Iwona
Zajkowska, Monika
Gacuta, Ewa
Puchnarewicz, Andrzej
Chrostek, Lech
Szmitkowski, Maciej
Lawicki, Slawomir
TI Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE M-CSF; MMP-2; TIMP-2; Cervical cancer; Tumor markers
ID M-CSF; MMP-2; TIMP-2; Cervical cancer; Tumor markers
AB Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitor (TIMP-2) may play an important role in the pathogenesis of cancer disease. We investigated the plasma levels and diagnostic power (ROC curve analysis) of M-CSF, MMP-2, TIMP-2 and tumor markers CA 125 and SCC-Ag in cervical cancer (CC) patients as compared to control group. The study included 89 patients with cervical cancer. The control group consisted of 50 healthy, untreated women. The plasma levels of M-CSF, MMP-2 and TIMP-2 were determined using ELISA, CA 125 and SCC-Ag – by CMIA method. The median levels of M-CSF, TIMP-2, SCC-Ag and CA 125 in the entire group of CC were significantly different than compared to the healthy women group. MMP-2 showed the highest value of sensitivity from all examined parameters (in stage I of CC – 93.10%, II – 82.76%, III and IV – 96.88%, total group – 92.05%). The highest specificity was obtained by M-CSF (86%). The area under the ROC curve (AUC) of M-CSF (0.8051) was the largest of all the tested parameters (even higher than commonly used tumor markers) in the group of cervical cancer. The combination of M-CSF, MMP-2 or TIMP- 2 with SCC antigen resulted in an increase AUCs in all cases (0.8760;0.7880;0.8081;respectively). The findings of this study suggest the usefulness of all examined parameters in the diagnostics of CC patients. Out of the tested substances, M-CSF also appears to be the best candidate for cancer diagnostics in all stages of the disease, based on ROC analysis.
C1 [Lubowicka, Emilia] Medical University of Bialystok, Department of Esthetic Medicine, Akademicka 3, 15-267 Bialystok, Poland.
[Zbucka-Kretowska, Monika] Medical University of Bialystok, Department of Reproduction and Gynecological Endocrinology, 15-276 Bialystok, Poland.
[Sidorkiewicz, Iwona] Medical University of Bialystok, Department of Reproduction and Gynecological Endocrinology, 15-276 Bialystok, Poland.
[Zajkowska, Monika] Medical University of Bialystok, Department of Biochemical Diagnostics, 15-269 Bialystok, Poland.
[Gacuta, Ewa] Medical University of Bialystok, Department of Perinatology, 15-276 Bialystok, Poland.
[Puchnarewicz, Andrzej] Provincial Hospital, Department of Urology, 15-278 Bialystok, Poland.
[Chrostek, Lech] Medical University of Bialystok, Department of Biochemical Diagnostics, 15-269 Bialystok, Poland.
[Szmitkowski, Maciej] Medical University of Bialystok, Department of Biochemical Diagnostics, 15-269 Bialystok, Poland.
[Lawicki, Slawomir] Medical University of Bialystok, Department of Population Medicine and Civilization Diseases Prevention, 15-269 Bialystok, Poland.
RP Lubowicka, E (reprint author), Medical University of Bialystok, Department of Esthetic Medicine, 15-267 Bialystok, Poland.
EM emila_lubowicka@wp.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 791
EP 800
DI 10.1007/s12253-019-00626-z
PG 10
ER
PT J
AU Wang, J
Zhao, Y
Xu, H
Ma, J
Liang, F
Zou, Q
Lin, F
AF Wang, Jianfeng
Zhao, Yan
Xu, Hongyan
Ma, Jun
Liang, Feihai
Zou, Qingxu
Lin, Fengwu
TI Silencing NID2 by DNA Hypermethylation Promotes Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung cancer; DNA methylation; NID2; Nude mice xenograft
ID Lung cancer; DNA methylation; NID2; Nude mice xenograft
AB To characterize the DNA methylation as well as exploring the relationship between NID2 methylation and the lung cancer development. Collecting chip data of 9 lung cancer samples and 11 adjacent normal samples from the Gene Expression Omnibus database. Tissues and cells NID2 gene methylation level was measured by methylation-specific PCR. NID2 mRNA level and protein level were validated by Real-Time PCR and Western blot separately. Functional study of lung cancer cells was performed with Cell Counting Kit-8 assay. Colony formation assay, Transwell assay, wound healing assay and low cytometry were performed. Finally, NID2 tumorigenesis in vivo was tested in nude mice xenograft models. Microarray analysis outcome present NID2 hypermethylation status in lung cancer tissues. High methylation and low mRNA expression levels of NID2 were detected. After NID2 demethylation or overexpression in cancer cells, cell viability, proliferation, migration as well as invasion ability decreased. Nevertheless, a significant enhancement in apoptosis rate were observed. Overexpressing NID2 or demethylation in lung cancer cells inhibited the tumorigenesis of lung cancer in nude mice. The mRNA and protein level of NID2 in tumors obtained from nude mice xenograft were unanimous with the in vitro assays’ outcome, which significantly decreased after overexpressing NID2 or demethylation. NID2 methylation reduces its expression level and promotes the development of lung cancer.
C1 [Wang, Jianfeng] China-Japan Union Hospital of Jilin University, Department of Radiotherapy, 130031 Changchun, Jilin, China.
[Zhao, Yan] The Second Hospital of Jilin University, Medical Examination Center, 130021 Changchun, Jilin, China.
[Xu, Hongyan] Jilin Second People’s Hospital, Department of Oncology, 132011 Jilin, Jilin, China.
[Ma, Jun] The Affiliated Hospital of Beihua University, Department of Radiotherapy, 132011 Jilin, Jilin, China.
[Liang, Feihai] The Second Affiliated Hospital of Guangxi Medical University, Department of Cardiothoracic Surgery, 530007 Nanning, Guangxi, China.
[Zou, Qingxu] China-Japan Union Hospital of Jilin University, Department of Thoracic Surgery, No. 126 freedom Avenue, 130031 Changchun, Jilin, China.
[Lin, Fengwu] China-Japan Union Hospital of Jilin University, Department of Thoracic Surgery, No. 126 freedom Avenue, 130031 Changchun, Jilin, China.
RP Lin, F (reprint author), China-Japan Union Hospital of Jilin University, Department of Thoracic Surgery, 130031 Changchun, China.
EM fengwulin@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 801
EP 811
DI 10.1007/s12253-019-00609-0
PG 11
ER
PT J
AU Regos, E
Karaszi, K
Reszegi, A
Kiss, A
Schaff, Zs
Baghy, K
Kovalszky, I
AF Regos, Eszter
Karaszi, Katalin
Reszegi, Andrea
Kiss, Andras
Schaff, Zsuzsa
Baghy, Kornelia
Kovalszky, Ilona
TI Syndecan-1 in Liver Diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Syndecan-1; Liver; Cirrhosis; Metastasis; Hepatocellular carcinoma
ID Syndecan-1; Liver; Cirrhosis; Metastasis; Hepatocellular carcinoma
AB Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans in the liver. Syndecan-1 is normally expressed on the surfaces of hepatocytes and cholangiocytes. Due to liver diseases the amount of syndecan-1 increases in the liver. Despite the emerging data of the biological function of syndecan-1, the clinical usefulness of this proteoglycan is still unknown. In our study we correlated syndecan-1 expression to clinicopathological data. We found that syndecan-1 proved to be a good marker for hepatitis C virus based hepatocellular carcinoma and increased with liver dysfunction.
C1 [Regos, Eszter] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Street 26, 1085 Budapest, Hungary.
[Karaszi, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Street 26, 1085 Budapest, Hungary.
[Reszegi, Andrea] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Street 26, 1085 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi street 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi street 93, 1091 Budapest, Hungary.
[Baghy, Kornelia] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Street 26, 1085 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi Street 26, 1085 Budapest, Hungary.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM koval@korb1.sote.hu
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Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK, 2010, Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J 277(19):3904–3923. , DOI 10.1111/j.1742-4658.2010. 07800.x
Manon-Jensen T, Itoh Y, Couchman JR, 2010, Proteoglycans in health and disease: the multiple roles of syndecan shedding. FEBS J 277(19):3876–3889. , DOI 10.1111/j.1742-4658. 2010.07798.x
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 813
EP 819
DI 10.1007/s12253-019-00617-0
PG 7
ER
PT J
AU Sawicka, E
Kratz, ME
Szymanska, B
Guzik, A
Wesolowski, A
Kowal, P
Pawlik-Sobecka, L
Piwowar, A
AF Sawicka, Ewa
Kratz, Maria Ewa
Szymanska, Beata
Guzik, Anna
Wesolowski, Artur
Kowal, Pawel
Pawlik-Sobecka, Lilla
Piwowar, Agnieszka
TI Preliminary Study on Selected Markers of Oxidative Stress, Inflammation and Angiogenesis in Patients with Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; Cancer grade and stage; Oxidative stress; Inflammation; Angiogenesis
ID Bladder cancer; Cancer grade and stage; Oxidative stress; Inflammation; Angiogenesis
AB In recent years, bladder cancer (BC) has been reported as one of the most commonly occurring cancers among older people, and its detection is still difficult. Therefore, there is a need to search for additional useful markers of disease. Some studies indicate the important roles of inflammation and oxidative stress (OS) in bladder tumour pathogenesis. The aim of this study was to examine the levels of selected markers of OS, inflammation and angiogenesis in blood plasma/serum samples derived from patients with BC, and a healthy control group. Moreover the degrees of change and strength of correlation between values of the analysed markers and tumour stage or grade were estimated. Concentrations of: malondialdehyde (MDA) and advanced oxidation protein products (AOPP), and total antioxidant status (TAS) divided into slow (TAS-s) and fast (TAS-f) antioxidants (spectrophotometric measurement), angiogenin (ANG) (immunoenzymatic method) and C-reactive protein (CRP) (immunoturbidimetric method) were determined in both the studied groups. The majority of values of the examined parameters were significantly higher among patients, while subfractions of TAS were significantly lower in comparison to the control group. Moreover, different values and different strengths of correlation between the examined parameters and cancer stage or grade were noticed. The most significant changes for CRP were observed in T2 and for MDA in G3, while the lowest TAS-f activity was revealed in G1 patients. Increased values of OS parameters, angiogenesis and inflammation markers, in combination with reduced TAS subfractions activity in BC are important in its pathogenesis and will be helpful in estimation of patients’ condition.
C1 [Sawicka, Ewa] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Toxicology, Borowska Street 211, 50-556 Wroclaw, Poland.
[Kratz, Maria Ewa] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Laboratory Diagnostics, Borowska Street 211, 50-556 Wroclaw, Poland.
[Szymanska, Beata] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Toxicology, Borowska Street 211, 50-556 Wroclaw, Poland.
[Guzik, Anna] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Toxicology, Borowska Street 211, 50-556 Wroclaw, Poland.
[Wesolowski, Artur] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Students Scientific Society at the Department of Toxicology, Borowska Street 211, 50-556 Wroclaw, Poland.
[Kowal, Pawel] Wroclaw Medical University, Department of Urology and Oncological Urology, H. M. Kamienskiego Street 73a, 51-124 Wroclaw, Poland.
[Pawlik-Sobecka, Lilla] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Laboratory Diagnostics, Borowska Street 211, 50-556 Wroclaw, Poland.
[Piwowar, Agnieszka] Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Toxicology, Borowska Street 211, 50-556 Wroclaw, Poland.
RP Kratz, ME (reprint author), Wroclaw Medical University, Faculty of Pharmacy with Division of Laboratory Diagnostics, Department of Laboratory Diagnostics, 50-556 Wroclaw, Poland.
EM ewa.kratz@umed.wroc.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 821
EP 831
DI 10.1007/s12253-019-00620-5
PG 11
ER
PT J
AU Arabkari, V
Clancy, E
Dwyer, MR
Kerin, JM
Kalinina, O
Holian, E
Newell, J
Smith, JT
AF Arabkari, Vahid
Clancy, Eoin
Dwyer, M Roisin
Kerin, J Michael
Kalinina, Olga
Holian, Emma
Newell, John
Smith, J Terry
TI Relative and Absolute Expression Analysis of MicroRNAs Associated with Luminal A Breast Cancer– A Comparison
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MicroRNAs; Luminal A breast cancer; Relative quantification; Absolute quantification
ID MicroRNAs; Luminal A breast cancer; Relative quantification; Absolute quantification
AB MicroRNAs, as small non-coding regulatory RNAs, play crucial roles in various aspects of breast cancer biology. They have prognostic and diagnostic value, which makes them very interesting molecules to investigate. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is the gold standard method to analyse miRNA expression in breast cancer patients. This study investigated two RT-qPCR methods (absolute and relative) to determine the expression of ten miRNAs in whole blood samples obtained from luminal A breast cancer patients compared to healthy controls. Whole blood samples were collected from 38 luminal A breast cancer patients and 20 healthy controls in Paxgene blood RNA tubes. Total RNA was extracted and analysed by relative and absolute RT-qPCR. For relative RT-qPCR, miR-16 was used as an endogenous control. For absolute RT-qPCR, standard curves were generated using synthetic miRNA oligonucleotides to determine the absolute copy number of each miRNA. Of the ten miRNAs that were analysed, the absolute RT-qPCR method identified six miRNAs (miR-16, miR-145, miR-155, miR- 451a, miR-21 and miR-486) that were upregulated and one miRNA (miR-195) that was downregulated. ROC curve and AUC analysis of the data found that the combination of three miRNAs (miR-145, miR-195 and miR-486) had the best diagnostic value for luminal A breast cancer with an AUC of 0.875, with 76% sensitivity and 81% specificity. On the other hand, the relative RTqPCR method identified two miRNAs (miR-155 and miR-486) that were upregulated and miR-195, which was downregulated. Using this approach, the combination of three miRNAs (miR-155, miR-195 and miR-486) was showed to have an AUC of 0.657 with 65% sensitivity and 69% specificity. We conclude that miR-16 is not a suitable normalizer for the relative expression profiling of miRNAs in luminal A breast cancer patients. Compared to relative quantification, absolute quantification assay is a better method to determine the expression level of circulating miRNAs in Luminal A breast cancer.
C1 [Arabkari, Vahid] NUI Galway, School of Natural Sciences, National Centre for Biomedical Engineering Science (NCBES), Molecular Diagnostics Research GroupGalway, Ireland.
[Clancy, Eoin] NUI Galway, School of Natural Sciences, National Centre for Biomedical Engineering Science (NCBES), Molecular Diagnostics Research GroupGalway, Ireland.
[Dwyer, M Roisin] NUI Galway, School of Medicine, Lambe Institute for Translational Research, Discipline of SurgeryGalway, Ireland.
[Kerin, J Michael] NUI Galway, School of Medicine, Lambe Institute for Translational Research, Discipline of SurgeryGalway, Ireland.
[Kalinina, Olga] NUI Galway, School of Mathematics, Statistics and Applied Mathematics, Clinical Research FacilityGalway, Ireland.
[Holian, Emma] NUI Galway, School of Mathematics, Statistics and Applied Mathematics, Clinical Research FacilityGalway, Ireland.
[Newell, John] NUI Galway, School of Mathematics, Statistics and Applied Mathematics, Clinical Research FacilityGalway, Ireland.
[Smith, J Terry] NUI Galway, School of Natural Sciences, National Centre for Biomedical Engineering Science (NCBES), Molecular Diagnostics Research GroupGalway, Ireland.
RP Arabkari, V (reprint author), NUI Galway, School of Natural Sciences, National Centre for Biomedical Engineering Science (NCBES), Molecular Diagnostics Research Group, Galway, Ireland.
EM v.arabkari1@nuigalway.ie
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 833
EP 844
DI 10.1007/s12253-019-00627-y
PG 12
ER
PT J
AU Soria-Comes, T
Palomar-Abril, V
Ureste, MM
Guerola, TM
Maiques, MIC
AF Soria-Comes, Teresa
Palomar-Abril, Vicente
Ureste, Martin Maria
Guerola, Tallon Monica
Maiques, Maestu Inmaculada Concepcion
TI Real-World Data of the Correlation between EGFR Determination by Liquid Biopsy in Non-squamous Non-small Cell Lung Cancer (NSCLC) and the EGFR Profile in Tumor Biopsy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR mutation status; Liquid biopsy; ctDNA; Cobas EGFR assay; Non-small cell lung cancer (NSCLC)
ID EGFR mutation status; Liquid biopsy; ctDNA; Cobas EGFR assay; Non-small cell lung cancer (NSCLC)
AB EGFR-mutated non-small cell lung cancer (NSCLC) has significant improved outcomes when treated with EGFR-tyrosine kinase inhibitors (TKI). Thus, EGFR-mutational status should be assessed at diagnosis and in the course of treatment with TKI. However, tissue samples are not always evaluable, and molecular profiling has been increasingly performed in cell-free tumor DNA (ctDNA) from blood samples. Our objective is to evaluate the reliability of ctDNA profiling in plasma samples in a real-world setting. We retrospectively analyzed the patients diagnosed with non-squamous NSCLC from May 2016 to December 2017 at Hospital Universitario Doctor Peset who had been tested for EGFR mutations in tissue and plasma samples. Both samples were sent to an external laboratory to perform the analysis by the cobas® EGFR assay. Percentage of agreement and concordance were calculated by kappa statistic. Of 102 patients reviewed, 89 were eligible. The overall EGFR mutation frequency was 18.6% for the evaluable tissue samples and 19.6% for evaluable plasma samples. Mutation status concordance between matched samples was 87.4%. Cohen’s kappa index (κ) = 0.6 (sensitivity 70.6%, specificity 91.7%, positive predictive value 66.7%, negative predictive value 93%). When concordance was stablished only in stage IV tumors κ = 0.7, suggesting a higher agreement in advanced disease. This real-world data suggest that plasma is a feasible sample for ctDNA EGFR mutation assessment. Results of ctDNA molecular profiling are reliable when using a validated technique such as the cobas® EGFR assay, especially in patients that cannot undergo a tissue biopsy.
C1 [Soria-Comes, Teresa] Hospital Universitario Doctor Peset, Department of Medical Oncology, 46017 Valencia, Comunitat Valenciana, Spain.
[Palomar-Abril, Vicente] Hospital Universitario Doctor Peset, Department of Medical Oncology, 46017 Valencia, Comunitat Valenciana, Spain.
[Ureste, Martin Maria] Hospital Universitario Doctor Peset, Department of Medical Oncology, 46017 Valencia, Comunitat Valenciana, Spain.
[Guerola, Tallon Monica] Hospital Universitario Doctor Peset, Department of Medical OncologyValencia, Comunitat Valenciana, Spain.
[Maiques, Maestu Inmaculada Concepcion] Hospital Universitario Doctor Peset, Department of Medical Oncology, 46017 Valencia, Comunitat Valenciana, Spain.
RP Soria-Comes, T (reprint author), Hospital Universitario Doctor Peset, Department of Medical Oncology, 46017 Valencia, Spain.
EM t.soria.comes@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 845
EP 851
DI 10.1007/s12253-019-00628-x
PG 7
ER
PT J
AU Zhao, R
Li, L
Yang, J
Niu, Q
Wang, H
Qin, X
Zhu, N
Shi, A
AF Zhao, Rui
Li, Lei
Yang, Jinbo
Niu, Qinfeng
Wang, Han
Qin, Xiaodong
Zhu, Ning
Shi, Anchen
TI Overexpression of Pyruvate Kinase M2 in Tumor Tissues Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pyruvate kinase M2; Hepatocellular carcinoma; Prognosis; Overall survival rate; Reoccurrence
ID Pyruvate kinase M2; Hepatocellular carcinoma; Prognosis; Overall survival rate; Reoccurrence
AB Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with a high degree of malignancy and a poor prognosis. The aim of this study was to investigate the relationship between expression of pyruvate kinase M2 (PKM2) and prognosis in patients with HCC. The expression levels of PKM2 and PKM1 in 86 cases of HCC were detected by immunohistochemistry. An H score was used to evaluate the expression of PKM, and all patients were further divided into PKM high expression and PKM low-expression groups. The relationship between PKM2 expression and the clinicopathological parameters and prognosis of patients were subsequently analyzed. Our data suggested that the expression level of PKM2 was significantly higher in HCC tissues than in adjacent tissues and the negatively expression of PKM1 in HCC tissues. Kaplan-Meier analysis revealed that PKM2 expression was strongly associated with survival in HCC patients (P = 0.001). The patients in the PKM2 high-expression group had significantly shorter survival times than the patients in the PKM2 low-expression group (hazard ratio for death, 2.358; 95% confidence interval [1.156, 4.812]; P = 0.018). In conclusion, these data indicate that PKM2 expression in HCC tissue samples can be used as a prognostic factor for patients with HCC and that high PKM2 expression is correlated with a poor prognosis in HCC patients.
C1 [Zhao, Rui] Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
[Li, Lei] Lanzhou University First Hospital, Department of Interventional Radiology, 730030 Lanzhou, China.
[Yang, Jinbo] Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
[Niu, Qinfeng] Baoji Affiliated Hospi, Xi’an Medical College, Baoguang Branch, 721006 Baoji, China.
[Wang, Han] Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
[Qin, Xiaodong] Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
[Zhu, Ning] Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
[Shi, Anchen] Lanzhou University, School of Basic Medical Sciences, 730000 Lanzhou, China.
RP Yang, J (reprint author), Lanzhou University, School of Life Sciences, 730000 Lanzhou, China.
EM zhaor@lzu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 853
EP 860
DI 10.1007/s12253-019-00630-3
PG 8
ER
PT J
AU Fernandez-Acenero, JM
Cruz, M
Sastre-Varela, J
Casal, IJ
Ceron Nieto, M
del Puerto-Nevado, L
Garcia-Foncillas, J
Cebrian, A
AF Fernandez-Acenero, Jesus Maria
Cruz, Mari
Sastre-Varela, Javier
Casal, Ignacio Jose
Ceron Nieto, Angeles Maria
del Puerto-Nevado, Laura
Garcia-Foncillas, Jesus
Cebrian, Arancha
TI TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon carcinoma; Chemotherapy; Early stage disease; Ubiquitin ligase; TRIM72; Recurrence; Immunohistochemistry
ID Colon carcinoma; Chemotherapy; Early stage disease; Ubiquitin ligase; TRIM72; Recurrence; Immunohistochemistry
AB Large bowel adenocarcinoma is one of the most frequent human neoplasms and despite recent insights into the pathophysiology and molecular basis of this disease, mortality remains high in advanced and metastatic cases. Most guidelines recommend adjuvant chemotherapy for tumours involving lymph nodes, but not for patients with localized stage I or II disease. However, it is well known that approximately 20% of stage II colorectal carcinoma patients eventually recur, mainly with distant or peritoneal involvement and show bad prognosis. It would be important to predict which patients are at increased risk of recurrence to guide potential adjuvant therapy use in this controversial setting. In this sense, only microsatellite stability has been proposed as a predictive tool in some guidelines. The tripartite motif family protein 72 (TRIM72) is a ubiquitin ligase, involved in the cell membrane repair machinery and known to be associated to insulin resistance. Its potential role in colon cancer has recently been proposed. The aim of this study is to determine the potential predictive value of TRIM72 immunohistochemical expression in stage II colon carcinoma. We have retrospectively reviewed a series of 95 patients with stage II colon microsatellite stable carcinomas operated with a curative intent at a single large tertiary hospital in Madrid (Spain) between 2006 and 2012. None of the patients received adjuvant chemotherapy. We reviewed the histopathological slides and constructed a tissue microarray (TMA) of three representative areas to perform immunohistochemical staining for TRIM72. In our series 30 patients (31.7%) recurred after a median follow-up of 17.5 months. Lack of immunohistochemical expression of TRIM72 in the tumor was significantly and independently associated to recurrence. A recent report by Chen et al. has shown that TRIM72 can be measured in plasma for colon carcinoma detection as an alternative to CEA or CA19.9, with lower levels in patients with carcinoma. Our report is the first one to show that lower immunohistochemical expression of TRIM72 predicts recurrence in colon stage II carcinoma. We feel this predictive influence can be related to its crucial role as a central regulator in many signaling pathways (PI3K-AKT, ERK).As an ubiquitin ligase, the lack of TRIM72 could increase the levels of several potential oncogenic molecules and therefore lead to a more aggressive phenotype. It remains to be shown whether chemotherapy could change the clinical behaviour of this bad prognosis group. We propose TRIM72 immunohistochemical analysis as a potential tool to predict recurrence risk in stage II colon carcinoma patients. Our results should be confirmed in larger series, but could open the way to management strategies refinement in this early stage group of patients.
C1 [Fernandez-Acenero, Jesus Maria] Hospital Clinico San Carlos, Department of Surgical Pathology, Avda Profesor Martin Lagos s, /n, 28040 Madrid, Spain.
[Cruz, Mari] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Sastre-Varela, Javier] Hospital Clinico San Carlos, Departments of OncologyMadrid, Spain.
[Casal, Ignacio Jose] Centro de Investigaciones Biologicas (CIB)Madrid, Spain.
[Ceron Nieto, Angeles Maria] Hospital Clinico San Carlos, Department of Surgical Pathology, Avda Profesor Martin Lagos s, /n, 28040 Madrid, Spain.
[del Puerto-Nevado, Laura] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Garcia-Foncillas, Jesus] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
[Cebrian, Arancha] University Hospital Fundacion Jimenez Diaz, Oncohealth Institute, Health Research Institute FJD-UAM, Translational Oncology DivisionMadrid, Spain.
RP Fernandez-Acenero, JM (reprint author), Hospital Clinico San Carlos, Department of Surgical Pathology, 28040 Madrid, Spain.
EM mgg10167@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 861
EP 865
DI 10.1007/s12253-019-00629-w
PG 5
ER
PT J
AU Collak, KF
Ummuhan, D
Sagir, F
AF Collak, Kisaayak Filiz
Ummuhan, Demir
Sagir, Fatma
TI YAP1 Is Involved in Tumorigenic Properties of Prostate Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE YAP1; pYAP1; Prostate cancer; Androgen receptor
ID YAP1; pYAP1; Prostate cancer; Androgen receptor
AB The Yes Associated Protein 1 (YAP1) is a transcriptional cofactor negatively regulated by Hippo Pathway. The dysregulation of the pathway has been shown to have a role in tumorigenesis and metastasis in several cancers including prostate cancer (PCa). In this study, YAP1 expression was upregulated in the whole cell lysates and cytoplasmic/nuclear extracts of AR negative (PC3) compared to AR positive (LNCaP) prostate cancer cell lines and primary prostate epithelial cells (PrePEC). pYAP1 expression elevated in LNCaP compared to PC3 and PrePEC in whole cell lysates and cytoplasmic extracts. The treatment of LNCaP and PC3 with YAP1-targeting siRNA oligonucleotides (YAP1 siRNA) significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA diminished the clonogenicity, anchorage-independent growth on soft agar, migration and invasion of PC3 cells. Co-IP/WB experiments revealed that YAP1 and AR formed a complex and ChIP/PCR results confirmed that YAP1 was bound to androgen response elements (ARE) core region of the prostate specific antigen (PSA) promoter. The loss of function experiments in LNCaP and PC3 revealed that YAP1 regulates proliferation, colony formation as well as anchorage-independent growth and potentially plays an important role in migration and invasion. Finally, analysis of publicly available data sets indicated that LNCaP had no YAP1 copy number alteration whereas PC3 had gain of YAP1 which was also reflected as an increase in the mRNA level. Moreover, YAP1 copy number gain and elevated YAP1 mRNA expression were detected in clinical samples analyzed in publicly available data sets. Taken together, these results suggested that YAP1 has a role in PCa tumorigenesis.
C1 [Collak, Kisaayak Filiz] Istanbul Medeniyet University, Faculty of Engineering and Natural Sciences, Molecular Biology and Genetics Department, Uskudar, 34700 Istanbul, Turkey.
[Ummuhan, Demir] Istanbul Medeniyet University, Faculty of Engineering and Natural Sciences, Molecular Biology and Genetics Department, Uskudar, 34700 Istanbul, Turkey.
[Sagir, Fatma] Istanbul Medeniyet University, Faculty of Engineering and Natural Sciences, Molecular Biology and Genetics Department, Uskudar, 34700 Istanbul, Turkey.
RP Collak, KF (reprint author), Istanbul Medeniyet University, Faculty of Engineering and Natural Sciences, Molecular Biology and Genetics Department, 34700 Istanbul, Turkey.
EM filiz.collak@medeniyet.edu.tr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 867
EP 876
DI 10.1007/s12253-019-00634-z
PG 10
ER
PT J
AU Roberto, MG
Lira, CR
Delsin, EL
Vieira, MG
Silva, OM
Hakime, GR
Yamashita, EM
Engel, EE
Scrideli, AC
Tone, GL
Brassesco, SM
AF Roberto, Molinari Gabriela
Lira, Caroline Regia
Delsin, Elis Lara
Vieira, Maciel Gabriela
Silva, Oliveira Marcela
Hakime, Guedes Rodrigo
Yamashita, Eiji Mauricio
Engel, Eduard Edgard
Scrideli, Alberto Carlos
Tone, Gonzaga Luiz
Brassesco, Sol Maria
TI microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-138; ROCK; microRNA; Osteosarcoma; Prognosis
ID miR-138; ROCK; microRNA; Osteosarcoma; Prognosis
AB Osteosarcoma (OS) is the most common primary malignant bone tumor with two peaks of incidence, in early adolescence and the elderly. Patients affected with this malignancy often present metastatic disease at diagnosis, and despite multimodality therapy, survival has not improved substantially over the past 3 decades. Recently, miR-138-5p, proposed as a crucial intracellular mediator of invasion, has been recognized to target the Rho-associated coiled-coil containing protein kinase 2 (ROCK2). Dysregulation of ROCK1 and ROCK2 was also described in OS, being associated to higher metastasis incidence and worse prognosis. Nonetheless, the specific roles of miR-138-5p in pediatric and young adult OS and its ability to modulate these kinases remain to be established. Thus, in the present study, the expression levels miR- 138-5p were evaluated in a consecutive cohort of exclusively pediatric and young adult primary OS samples. In contrast to previous reports that included adult tissues, our results showed upregulation of miR-138-5p associated with reduced event-free survival and relapsed cases. In parallel, ROCK1 mRNA levels were significantly reduced in tumor samples and negatively correlated with miR-138-5p. Similar correlations were observed after studying the profiles of ROCK1 and ROCK2 by immunohistochemistry. Our data present miR-138-5p as a consistent prognostic factor in pediatric and young adult OS, reinforcing its participation in the post-transcriptional regulation of ROCK kinases.
C1 [Roberto, Molinari Gabriela] University of Sao Paulo, Ribeirao Preto School of Medicine, Regional Blood CenterSao Paulo, Brazil.
[Lira, Caroline Regia] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of PediatricsSao Paulo, Brazil.
[Delsin, Elis Lara] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of GeneticsSao Paulo, Brazil.
[Vieira, Maciel Gabriela] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of GeneticsSao Paulo, Brazil.
[Silva, Oliveira Marcela] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell BiologySao Paulo, Brazil.
[Hakime, Guedes Rodrigo] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
[Yamashita, Eiji Mauricio] University of Sao Paulo, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, Department of BiologySao Paulo, Brazil.
[Engel, Eduard Edgard] University of Sao Paulo, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, Department of BiologySao Paulo, Brazil.
[Scrideli, Alberto Carlos] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell BiologySao Paulo, Brazil.
[Tone, Gonzaga Luiz] University of Sao Paulo, Ribeirao Preto School of Medicine, Department Cell BiologySao Paulo, Brazil.
[Brassesco, Sol Maria] University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor SystemSao Paulo, Brazil.
RP Brassesco, SM (reprint author), University of Sao Paulo, Ribeirao Preto School of Medicine, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Sao Paulo, Brazil.
EM solbrassesco@usp.br
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 877
EP 883
DI 10.1007/s12253-019-00633-0
PG 7
ER
PT J
AU Kamyab-Hesary, K
Ghanadan, A
Balighi, K
Mousavinia, FS
Nasimi, M
AF Kamyab-Hesary, Kambiz
Ghanadan, Alireza
Balighi, Kamran
Mousavinia, Faeze Seyede
Nasimi, Maryam
TI Immunohistochemical Staining in the Assessment of Melanoma Tumor Thickness
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Breslow thickness; Immunohistochemical staining
ID Melanoma; Breslow thickness; Immunohistochemical staining
AB Vertical tumor thickness has great influence in the prognosis and staging of melanoma. The aim of this study was determination of the differences between melanoma tumor thickness in conventional hematoxylin and eosin (H&E) and immunohistochemical techniques. Thirty-six biopsy specimens were included in our study. For each sample, four adjacent tissue sections were stained with H&E, in addition S-100, Melan- A and HMB-45 staining was performed on the next serial sections. The mean thickness of tumor invasion was 2.16, 2.38, 2.22 and 2.29 mm in H&E, S-100, HMB45 and Melan-A sections evaluation, respectively. The mean difference of the Breslow thickness between H&E and S-100 and also, between H&E and Melan-A stained slides were statistically significant (p˂0.05) while no difference was found in the tumor thickness of the H&E and HMB45 staining evaluation (p = 0.278). Greater tumor thickness was observed in 25 lesions (69.4%) with S-100, 20 lesions (55.5%) with Melan-A and 17 (47.2%) lesions in HMB-45 rather than H&E staining. Conclusively, it appears that H&E staining cannot prove the actual size of melanoma invasion in some cases and immunohistochemical examination can be a complementary method in this situations. Of the melanoma associated immunomarkers, the combination of S-100 and Melan-A staining may suffice to measure depth of tumor invasion.
C1 [Kamyab-Hesary, Kambiz] Tehran University of Medical Sciences, Razi Hospital, Department of DermatopathologyTehran, Iran.
[Ghanadan, Alireza] Tehran University of Medical Sciences, Razi Hospital, Department of DermatopathologyTehran, Iran.
[Balighi, Kamran] Tehran University of Medical Sciences, Razi Hospital, Department of Dermatology, Vahdate Eslami Street, 1199663911 Tehran, Iran.
[Mousavinia, Faeze Seyede] Shahid Beheshti University of Medical SciencesTehran, Iran.
[Nasimi, Maryam] Tehran University of Medical Sciences, Razi Hospital, Department of Dermatology, Vahdate Eslami Street, 1199663911 Tehran, Iran.
RP Nasimi, M (reprint author), Tehran University of Medical Sciences, Razi Hospital, Department of Dermatology, 1199663911 Tehran, Iran.
EM Nsm.maryam@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 885
EP 891
DI 10.1007/s12253-019-00635-y
PG 7
ER
PT J
AU Huang, Q
Li, X
Huang, Z
Yu, F
Wang, X
Wang, Sh
He, Z
Lin, J
AF Huang, Qingshan
Li, Xiaodong
Huang, Zhen
Yu, Fengqiang
Wang, Xinwen
Wang, Shenglin
He, Zhizhen
Lin, Jianhua
TI ACTN4 Promotes the Proliferation, Migration, Metastasis of Osteosarcoma and Enhances its Invasive Ability through the NF-κB Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; ACTN4; Invasion; Metastasis; NF-κB
ID Osteosarcoma; ACTN4; Invasion; Metastasis; NF-κB
AB Alpha-actinin-4 (ACTN4) is associated with different types of tumors, but its role in osteosarcoma (OS) is not known. We aimed to investigate the effect of ACTN4 on the growth, migration, invasion and metastasis of OS. We further explored the possible mechanism of how ACTN4 affects the development of OS. First, the expression of ACTN4 in OS tissues and OS cell lines was analyzed by PCR. Second, the role of ACTN4 in the development of OS was explored by the proliferation, scratch, and invasion assays. We further explored the effect of ACTN4 on OS growth in an orthotopic xenograft model of nude mice. In addition, we used hematoxylin and eosin (HE) staining of lung tissues in nude mice to observe the effect of ACTN4 on lung metastasis of OS. Finally, rescue experiments further investigated the role of NF-κB on ACTN4 in the development of OS. ACTN4 was highly expressed in OS tissues and OS cell lines. In vitro experiments demonstrated that reducing ACTN4 expression inhibited the proliferation, migration, and invasion of OS. In contrast, overexpression of ACTN4 promotes these effects. In vivo experiments further validated that ACTN4 promoted the growth of OS. The HE staining of lungs in nude mice revealed that ACTN4 promoted lung metastasis of OS. In addition, we found that ACTN4 enhanced the ability of OS to invade, through the NF-κB pathway. ACTN4 promotes the proliferation, migration, metastasis of OS and enhances its invasion ability through the NF-κB pathway
C1 [Huang, Qingshan] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Li, Xiaodong] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Huang, Zhen] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Yu, Fengqiang] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Wang, Xinwen] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Wang, Shenglin] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[He, Zhizhen] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
[Lin, Jianhua] The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
RP Lin, J (reprint author), The First Affiliated Hospital of Fujian Medical University, Department of Orthopedics, 350005 Fuzhou, China.
EM jianhua1@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 893
EP 904
DI 10.1007/s12253-019-00637-w
PG 12
ER
PT J
AU Jorgo, K
Polgar, Cs
Major, T
Stelczer, G
Herein, A
Pocza, T
Gesztesi, L
Agoston, P
AF Jorgo, Kliton
Polgar, Csaba
Major, Tibor
Stelczer, Gabor
Herein, Andras
Pocza, Tamas
Gesztesi, Laszlo
Agoston, Peter
TI Acute and Late Toxicity after Moderate Hypofractionation with Simultaneous Integrated Boost (SIB) Radiation Therapy for Prostate Cancer. A Single Institution, Prospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Simultaneous integrated boost; Moderate hypofractionation; Intensity-modulated radiotherapy; Image-guided radiotherapy
ID Prostate cancer; Simultaneous integrated boost; Moderate hypofractionation; Intensity-modulated radiotherapy; Image-guided radiotherapy
AB To evaluate the acute and late toxicity using moderately hypofractionated, intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) to prostate for patients with intermediate and high risk prostate cancer. From 2015 to 2017, 162 patients were treated with IMRT with SIB to the prostate. IMRT plans were designed to deliver 50.4Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes (whole pelvis radiotherapy, WPRT) while simultaneously delivering 57.4 Gy in 28 fractions (2.05 Gy/fraction) to the seminal vesicles and 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate for high risk patients. For intermediate risk patients the same technique was applied, without WPRT. Acute and cumulative late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) scoring system. Of the 162 patients enrolled, 156 (96%) completed the treatment as planned. The median follow-up time was 30 months. Seventy-eight patients (48.2%) were treated with WPRT. The rate of acute grade ≥ 2 GI and GU toxicities in all patients were 22% and 58%, respectively. The rate of cumulative late grade ≥ 2 GI and GU toxicities were 11% and 17%, respectively. Acute grade 3 GI and GU toxicities occurred in 1% and 1%. Late grade 3 GI and GU side effects occurred in 5% and 4%, respectively. None of the patients developed grade ≥ 4 toxicity. IMRT with SIB technique using moderate hypofractionation to the prostate is feasible treatment option for intermediate and high risk patients, associated with low rate of severe GU and GI toxicities.
C1 [Jorgo, Kliton] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Major, Tibor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Stelczer, Gabor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Herein, Andras] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Pocza, Tamas] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Gesztesi, Laszlo] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Agoston, Peter] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
RP Jorgo, K (reprint author), National Institute of Oncology, Center of Radiotherapy, 1122 Budapest, Hungary.
EM jorgokliton@gmail.com
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McCammon R, Rusthoven KE, Kavanagh B et al, 2009, Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys 75:413–420 46. Engels B, Soete G, Tournel K et al, 2009, Helical tomotherapy with simultaneous integrated boost for high risk and lymph node positiveprostate cancer: early report on acute and late toxicity. Technol Cancer Res Treat 8:353–9 48. Adkison JB, McHaffie DR, Bentzen SM et al, 2012, Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for highrisk prostate cancer. Int J Radiat Oncol Biol Phys 82:184–190 49. Alongi F, Fogliata A, Navarria P et al, 2012, Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy, RapidArc, for prostate cancer. Report of feasibility and acute toxicity. Strahlenther Onkol 188:990–996 50. Chang MG, Mukhopadhyay N, Holdford D, Skinner V, Saraiya S, Moghanaki D, Anscher MS, 2018, Phase 1/2 study of hypofractionated intensity-modulated radiation therapy for prostate cancer including simultaneously integrated boost. Pract Radiat Oncol 8:e149–e157 51. Magli A, Moretti E, Tullio A, Giannarini G, Tonetto F, Urpis M, Crespi M, Foti C, Prisco A, Polsinelli M, de Giorgi G, Bravo G, Scalchi P, TrovoM(2018, Hypofractionated simultaneous integrated boost, IMRT-SIB, with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial. Prostate Cancer Prostatic Dis 21:269–276
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 905
EP 912
DI 10.1007/s12253-019-00623-2
PG 8
ER
PT J
AU Thangarasu, R
Pachaiappan, P
Subbaiyan, Th
AF Thangarasu, Rajakumar
Pachaiappan, Pugalendhi
Subbaiyan, Thilagavathi
TI Anti-Estrogenic and Anti-Cell Proliferative Effect of Allyl Isothiocyanate in Chemoprevention of Chemically Induced Mammary Carcinogenesis in Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 7-12-dimethylbenz(a)anthracene; Allyl isothiocyanate; Cell proliferation; Chemoprevention; Mammary carcinogenesis; N-methyl-N-nitrosourea
ID 7-12-dimethylbenz(a)anthracene; Allyl isothiocyanate; Cell proliferation; Chemoprevention; Mammary carcinogenesis; N-methyl-N-nitrosourea
AB The anti-estrogenic and anti-cell proliferative effect of allyl isothiocyanate (AITC) was carried out by analyzing the status of sex hormones and its receptors and cell proliferative markers in chemically induced mammary carcinogenesis in rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) and MNU (50 mg/kg bw) injected subcutaneously near mammary gland. RT-PCR, western blotting and immunohistochemical analysis of mammary tissues show an upregulation of ER-α, PR, aromatase, PCNA, cyclin D1 and AgNORs staining and down regulation of p53 expression as well as plasma estradiol, prolactin and testosterone levels increased in DMBA and MNU-induced tumor bearing rats. Oral administration of AITC at a dose of 20 mg/kg bw restored the levels of sex hormones and its receptors, aromatase, cell proliferative markers and AgNORs staining near to normal levels. Molecular docking studies also supported these findings. The results suggest that anti-estrogenic and anti-proliferative effect of AITC prevent the development of DMBA and MNU-induced mammary carcinogenesis in rat.
C1 [Thangarasu, Rajakumar] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
[Pachaiappan, Pugalendhi] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
[Subbaiyan, Thilagavathi] Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
RP Pachaiappan, P (reprint author), Annamalai University, Faculty of Science, Department of Biochemistry and Biotechnology, 608 002 Tamil Nadu, India.
EM pugalau@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 913
EP 925
DI 10.1007/s12253-019-00638-9
PG 13
ER
PT J
AU Sohn, YS
Lee, JJ
Lee, HJ
AF Sohn, Young Seo
Lee, Jeong-Ju
Lee, Hyuk Jae
TI Molecular Profile and Clinicopathologic Features of Follicular Variant Papillary Thyroid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NIFTP; BRAF; RAS; Thyroid neoplasm
ID NIFTP; BRAF; RAS; Thyroid neoplasm
AB The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has an indolent clinical behavior. Recently, it was proposed that this tumor type should be reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). To characterize NIFTPs, we evaluated the molecular and clinicopathologic characteristics of each FVPTC subtype. This study enrolled 29 patients with FVPTC who underwent thyroidectomy between January 2007 and June 2017. They were classified as non-invasive encapsulated FVPTC (NIFTP, n = 10), invasive encapsulated FVPTC (n = 11), and infiltrative FVPTC (n = 8) by two independent pathologists. Genetic alterations were analyzed by targeted next-generation sequencing using formalin-fixed, paraffin-embedded tissue samples and the clinicopathologic characteristics were retrospectively reviewed. There was no difference in preoperative cytologic classification between NIFTPs and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class VI than the encapsulated type (50% versus 9.5%; P = 0.033). Lymph node metastasis was not found in NIFTPs. There was no BRAFV600E mutation in NIFTPs, whereas one of 11 invasive encapsulated FVPTCs and three of 8 infiltrative FVPTCs harbored BRAFV600E. RAS mutations were frequently detected in encapsulated FVPTCs (5 of 10 NIFTPs and 4 of 11 invasive encapsulated FVPTCs) but were only detected in one case of the infiltrative type. There were no differences in molecular or clinicopathologic profiles between non-invasive and invasive encapsulated FVPTCs, except for lymph node metastasis and the presence of BRAFV600E. NIFTP has favorable pathologic characteristics with a high frequency of RAS mutations.
C1 [Sohn, Young Seo] Hanyang University College of Medicine, Myongji Hospital, Department of Internal Medicine, Division of Endocrinology and MetabolismGoyang, South Korea.
[Lee, Jeong-Ju] Hanyang University College of Medicine, Myongji Hospital, Department of PathologyGoyang, South Korea.
[Lee, Hyuk Jae] Hanyang University College of Medicine, Myongji Hospital, Department of Internal Medicine, Division of Endocrinology and MetabolismGoyang, South Korea.
RP Sohn, YS (reprint author), Hanyang University College of Medicine, Myongji Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Goyang, South Korea.
EM drsohnsy@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 927
EP 936
DI 10.1007/s12253-019-00639-8
PG 10
ER
PT J
AU Qi, J
Ni, W
AF Qi, Junhui
Ni, Wei
TI Attenuation of MAMLD1 Expression Suppresses the Growth and Migratory Properties of Gonadotroph Pituitary Adenomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pituitary adenoma; MAMLD1; CXorf6; Notch
ID Pituitary adenoma; MAMLD1; CXorf6; Notch
AB Gonadotroph pituitary adenomas (GPAs) constitute approximately 15–40% of pituitary tumors. Some GPAs can be highly infiltrative, making full surgical resection challenging and increasing the risk of recurrence. The transcriptional co-activator Mastermind-Like Domain Containing 1 (MAMLD1, CXorf6, F18) is involved in regulating signaling pathways important in pituitary tumorigenesis, including the Notch signaling pathway. However, MAMLD1’s role in GPA remains unknown. GPA biopsies were collected from 96 patients following surgery, who were monitored until tumor recurrence. GPA tissue was used for immunohistochemistry. The murine GPA cell lines αT3 and LβT2 were used for in vitro experiments. Lentiviral constructs were employed for MAMLD1 knockdown (KD) and dominant negative (DN) mutant experiments. Quantitative real-time PCR (qPCR) and Western blotting of MAMLD1 and Notch2 were performed. MTT and Transwell assays were used to quantify proliferation and migration, respectively. An αT3 xenograft model was established in athymic nude mice followed by fluorescent IHC of xenograft tumors. MAMLD1 and Notch2 levels correlated positively with aggressive GPAs. Increased MAMLD1 levels correlated with shortened recurrence-free survival (RFS) in aggressive GPA patients. Moreover, MAMLD1 expression independently affected patient RFS according to multivariate Cox regression. In vitro, MAMLD1 KD in the murine GPA cell lines attenuated their proliferation and migration and Notch2 expression. Additionally, DN MAMLD1L210X lowered their proliferative and migratory capacity. MAMLD1 KD suppressed tumor growth and Notch2 expression in murine xenografts. MAMLD1 may serve as a predictor of GPA patient outcome and may also be leveraged as a possible therapeutic target for aggressive GPA tumors.
C1 [Qi, Junhui] The Second Hospital of Yunnan Province, Department of NeurosurgeryKunming, Yunnan Province, China.
[Ni, Wei] The Third Affiliated Hospital of Kunming Medical University, Department of Neurosurgery, No. 519, Kunzhou Road, 650118 Kunming, Yunnan Province, China.
RP Ni, W (reprint author), The Third Affiliated Hospital of Kunming Medical University, Department of Neurosurgery, 650118 Kunming, China.
EM niweikm2018@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 937
EP 946
DI 10.1007/s12253-019-00615-2
PG 10
ER
PT J
AU Gao, C
Shen, J
Meng, ZX
He, XF
AF Gao, Cao
Shen, Jiang
Meng, Zhi-Xiu
He, Xiao-Feng
TI Sevoflurane Inhibits Glioma Cells Proliferation and Metastasis through miRNA-124-3p/ROCK1 Axis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sevoflurane; Glioma; miRNA-124-3p; ROCK1
ID Sevoflurane; Glioma; miRNA-124-3p; ROCK1
AB Malignant glioma is the most common primary malignancy in the brain. It is aggressive, highly invasive, and destructive. Studies have shown that sevoflurane can affect the invasion and migration of a variety of malignant tumors. However, its effects on human glioma cells and related mechanisms are not clear. Cultured U251 and U87 cells were pretreated with sevoflurane. The effect of sevoflurane on cell proliferation, migration, apoptosis and invasion ability were evaluated by MTT, wound healing assay, cell apoptosis and transwell assays, respectively. miRNA-124-3p and ROCK1 signaling pathway genes expression in sevoflurane treated cell lines was measured by quantitative real-time PCR (qRT-PCR) and western blotting analysis. The potential target genes of miRNA were predicted by online software. Luciferase reporter assay was employed to validate the direct targeting of ROCK1 by miRNA-124-3p. In present studies, sevoflurane inhibits glioma cells proliferation, invasion and migration. Additionally, inversely correlation between miR-124-3p and ROCK1 expression in sevoflurane treated glioma cells was observed. Furthermore, sevoflurane inhibits glioma cells proliferation, migration and invasion through miR-124-3p/ROCK1 axis. Taken together, our study revealed that sevoflurane can inhibit glioma cell proliferation, invasion and migration. Its mechanism may be related to the upregulation of miR-124-3p, which suppresses ROCK1 signaling pathway. The results of the study will help to understand the pharmacological effects of inhaled general anesthetics more comprehensively and help to provide an experimental basis for selecting more reasonable anesthetics for cancer patients.
C1 [Gao, Cao] The Third Affiliated Hospital of Soochow University, Department of Anesthesiology, 213002 Changzhou, China.
[Shen, Jiang] The Third Affiliated Hospital of Soochow University, Department of Anesthesiology, 213002 Changzhou, China.
[Meng, Zhi-Xiu] The Third Affiliated Hospital of Soochow University, Department of Anesthesiology, 213002 Changzhou, China.
[He, Xiao-Feng] The Third Affiliated Hospital of Soochow University, Department of Anesthesiology, 213002 Changzhou, China.
RP He, XF (reprint author), The Third Affiliated Hospital of Soochow University, Department of Anesthesiology, 213002 Changzhou, China.
EM hexiaofeng1567@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 947
EP 954
DI 10.1007/s12253-019-00597-1
PG 8
ER
PT J
AU Thorpe, D
Butler, R
Sultani, M
Vanhoecke, B
Stringer, A
AF Thorpe, Daniel
Butler, Ross
Sultani, Masooma
Vanhoecke, Barbara
Stringer, Andrea
TI Irinotecan-Induced Mucositis Is Associated with Goblet Cell Dysregulation and Neural Cell Damage in a Tumour Bearing DA Rat Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mucositis; Chemotherapy; Enteric nervous system; Mucus
ID Mucositis; Chemotherapy; Enteric nervous system; Mucus
AB Irinotecan–induced mucositis is a major oncological problem. Goblet cells secrete mucus, protecting the intestinal mucosa, with secretion altered during mucositis. The enteric nervous system is involved in regulating gut motility and secretion. The aim of this study was to determine whether enteric neural cells and goblet cells are altered following irinotecan treatment. Tumour-bearing Dark Agouti rats were administered a single dose of 175 mg/kg of irinotecan intraperitoneally and 0.01 mg/kg atropine subcutaneously. Experimental and untreated control rats were killed at times 6, 24, 48, 72, 96 and 120 h after treatment. Jejunum and colon samples were formalin fixed. Haematoxylin and eosin staining, Alcian Blue-PAS staining, and immunohistochemistry with S-100 antibody (neural cell marker) were carried out. Statistical analyses were carried out using Kruskal-Wallis test with Dunns post test, Mann Whitney U test and nonlinear regression. Total goblet cells decreased at 72 h compared with controls in the colon (p < 0.05). The percentage of cavitated goblet cells decreased compared to all other time points at 120 h in the colon. The number of S-100 positive cells in the submucosal plexus decreased in the colon (p = 0.0046) and in the myenteric plexus of the jejunum and colon (p = 0.0058 and p = 0.0022, respectively), when comparing treated with control. Enteric ganglia in the myenteric plexus of the jejunum decreased at 24 h and 96 h. Irinotecan-induced mucositis is associated with increases in mucus secretion, and enteric neural cell change. These changes may contribute to the pathophysiology of mucositis through the dysregulation of neural signalling.
C1 [Thorpe, Daniel] University of South Australia, School of Pharmacy and Medical Sciences, 5001 Adelaide, Australia.
[Butler, Ross] University of South Australia, School of Pharmacy and Medical Sciences, 5001 Adelaide, Australia.
[Sultani, Masooma] University of South Australia, School of Medical Sciences, 5001 Adelaide, Australia.
[Vanhoecke, Barbara] University of Ghent, Center for Microbiology Ecology and TechnologyGhent, Belgium.
[Stringer, Andrea] University of South Australia, School of Pharmacy and Medical Sciences, 5001 Adelaide, Australia.
RP Thorpe, D (reprint author), University of South Australia, School of Pharmacy and Medical Sciences, 5001 Adelaide, Australia.
EM Daniel.thorpe@unisa.edu.au
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 955
EP 965
DI 10.1007/s12253-019-00644-x
PG 11
ER
PT J
AU Bai, Y
Wang, J
Gao, Z
Dai, E
AF Bai, Yuru
Wang, Jiabao
Gao, Zhihua
Dai, Erqing
TI Identification and Verification of Two Novel Differentially Expressed Proteins from Non-neoplastic Mucosa and Colorectal Carcinoma Via iTRAQ Combined with Liquid Chromatography-Mass Spectrometry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Proteomics; Colorectal cancer; Isobaric mass tags for relative and absolute quantification; Multidimensional liquid chromatography and tandem mass spectrometry; Differential expressed proteins
ID Proteomics; Colorectal cancer; Isobaric mass tags for relative and absolute quantification; Multidimensional liquid chromatography and tandem mass spectrometry; Differential expressed proteins
AB Recurrence or metastasis of colorectal cancer (CRC) is common following surgery and/or adjuvant therapy, particularly in patients with an advanced stage of the cancer. Identifying key molecular markers of CRC is beneficial for early diagnosis and early treatment, which may eventually improve the prognosis of patients with CRC. Isobaric mass tags for relative and absolute quantification (iTRAQ) in combination with multidimensional liquid chromatography and tandem mass spectrometry (LC-MS/ MS) were used to identify differentially expressed proteins between CRC tissues and paired adjacent normal mucosa. Among the 105 patients, adenocarcinoma was the most common CRC subtype, stage III was the most common Tumor-Node-Metastasis stage and high levels of Ki-67 indicated the rapid proliferation of tumor cells in the samples. The LC-MS/MS-based iTRAQ technology identified 271 differentially expressed proteins, with 130 upregulated proteins and 141 downregulated proteins. Bioinformatics analysis revealed that golgin subfamily A member 2 (GOLGA2) and heterogeneous nuclear ribonucleoprotein D0 (hnRNPD) were located in the center of the upregulated protein network, and were closely associated with the development of CRC. The upregulation of GOLGA2 and hnRNPD was further verified in human tissues using western blotting and immunohistochemistry. GOLGA2 and hnRNPD were identified as two novels differentially expressed proteins in human CRC. Furthermore, the LCMS/ MS-based iTRAQ proteomic approach is a useful tool for searching and identifying differentially expressed proteins, and may be used to provide a comprehensive understanding of the processes that mediate the development of CRC.
C1 [Bai, Yuru] Characteristic Medical Center of Chinese People’s Armed Police Forces, Department of Military Medical and Health Care, 300162 Tianjin, China.
[Wang, Jiabao] Characteristic Medical Center of Chinese People’s Armed Police Forces, Department of Military Medical and Health Care, 300162 Tianjin, China.
[Gao, Zhihua] Characteristic Medical Center of Chinese People’s Armed Police Forces, Department of Military Medical and Health Care, 300162 Tianjin, China.
[Dai, Erqing] Characteristic Medical Center of Chinese People’s Armed Police Forces, Department of Military Medical and Health Care, 300162 Tianjin, China.
RP Dai, E (reprint author), Characteristic Medical Center of Chinese People’s Armed Police Forces, Department of Military Medical and Health Care, 300162 Tianjin, China.
EM erqingdai@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 967
EP 976
DI 10.1007/s12253-019-00651-y
PG 10
ER
PT J
AU Kim, U
Kim, CY
Lee, MJ
Oh, H
Ryu, B
Kim, J
Park, JH
AF Kim, Ukjin
Kim, C-Yoon
Lee, Min Ji
Oh, Hanseul
Ryu, Bokyeong
Kim, Jin
Park, Jae-Hak
TI Phloretin Inhibits the Human Prostate Cancer Cells Through the Generation of Reactive Oxygen Species
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Phloretin; Prostate cancer; ROS; Redox homeostasis; Wnt/β-catenin signaling
ID Phloretin; Prostate cancer; ROS; Redox homeostasis; Wnt/β-catenin signaling
AB Phloretin is a flavonoid with known anticancer activities. However, we do not fully understand how phloretin mitigates prostate cancer on the molecular level. In the present study, we examined changes in proliferation, colony formation, and migration after phloretin treatment in human prostate cancer cells PC3 and DU145. We measured reactive oxygen species (ROS) and gene expression. Phloretin increased ROS and suppressed cell proliferation, migration, and colony formation in both cell lines. Additionally, phloretin treatment increased oxidative stress, as demonstrated through lower antioxidant enzymes (catalase, SOD2, Gpx1, Gpx3). In addition, their regulator CISD2 decreased in expression. We also found that increased ROS significantly downregulated multiple components of the Wnt/β-catenin signaling pathway (β-catenin, TCF4, FoxA2, c-Myc) and Twist1. Thus, anticancer activity of phloretin against human prostate cancer cells occurs through generating ROS to influence Wnt/β- catenin signaling. The results of this study suggest that phloretin has a therapeutic effect on prostate cancer in vitro, inhibiting the proliferation and migration of cancer cell lines PC3 and DU145. The mechanism of phloretin appears to be increasing ROS production. We thus recommend phloretin as a promising anticancer therapeutic agent.
C1 [Kim, Ukjin] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Kim, C-Yoon] Konkuk University, School of Medicine, Department of Stem Cell Biology, 05029 Seoul, South Korea.
[Lee, Min Ji] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Oh, Hanseul] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Ryu, Bokyeong] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Kim, Jin] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Park, Jae-Hak] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
RP Park, JH (reprint author), Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
EM pjhak@snu.ac.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 977
EP 984
DI 10.1007/s12253-019-00643-y
PG 8
ER
PT J
AU Oguh-Olayinka, L
Agarwal, V
Ranatunge, D
Campbell, A
Laufer, S
Cawkwell, Ly
Lind, JM
AF Oguh-Olayinka, Lily
Agarwal, Vijay
Ranatunge, Dulani
Campbell, Anne
Laufer, Stefan
Cawkwell, Lynn
Lind, J Michael
TI The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Arachidonic acid; Cyclooxygenase; Immunohistochemistry; Lipoxygenase; Mesothelioma
ID Arachidonic acid; Cyclooxygenase; Immunohistochemistry; Lipoxygenase; Mesothelioma
AB Advanced malignant pleural mesothelioma (MPM) has an extremely poor prognosis with limited chemotherapy options, therefore the identification of new therapeutic targets would aid in disease management. Arachidonic acid is metabolised by cyclooxygenase and lipoxygenase enzymes. The lipoxygenase isoenzymes 5-LOX and 12-LOX have been implicated in carcinogenesis. We aimed to examine 5-LOX and 12-LOX protein expression in a large retrospective series of mesothelioma samples. Further to this, the in vitro cytotoxic effects of lipoxygenase pathway inhibitors were investigated in mesothelioma cells. Archival samples from 83 patients with MPM were examined by immunohistochemistry for expression of the 5-LOX and 12-LOX proteins. The MTS assay was used to assess cell viability following 72 h treatment with the lipoxygenase pathway inhibitors baicalein, licofelone, MK-886 and zileuton in the MPM cell lines NCI-H2052, NCI-H2452 and MSTO-211H. Positive 12-LOX protein expression was recorded in 69/83 (83%) and positive 5-LOX expression was observed in 56/77 (73%) of MPM tissue samples. Co-expression of 5-LOX with 12-LOX was seen in 46/78 (58%) of MPM samples. Positive expression of 5-LOX, 12- LOX and COX-2 proteins was identified in the NCI-H2052, NCI-H2452 and MSTO-211H MPM cell lines. Baicalein (12-LOX and 15-LOX inhibitor) was effective in 3/3 MPM cell lines at low concentrations with an IC50 range of 9.6 μM to 20.7 μM. We have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease. We have demonstrated that the inhibition of the LOX pathway using baicalein may be effective as a novel treatment for MPM, however further human pharmacokinetic studies are required in order to establish whether the concentration used in vitro is clinically achievable.
C1 [Oguh-Olayinka, Lily] Castle Hill Hospital, Hull York Medical School, Research Laboratories, Daisy Building, HU16 5JQ Hull, UK.
[Agarwal, Vijay] Castle Hill Hospital, Hull York Medical School, Research Laboratories, Daisy Building, HU16 5JQ Hull, UK.
[Ranatunge, Dulani] Castle Hill Hospital, Hull York Medical School, Research Laboratories, Daisy Building, HU16 5JQ Hull, UK.
[Campbell, Anne] Hull and East Yorkshire NHS Trust, Histopathology DepartmentHull, UK.
[Laufer, Stefan] Eberhard Karls University, Department of Pharmaceutical ChemistryTubingen, Germany.
[Cawkwell, Lynn] Castle Hill Hospital, Hull York Medical School, Research Laboratories, Daisy Building, HU16 5JQ Hull, UK.
[Lind, J Michael] Castle Hill Hospital, Hull York Medical School, Research Laboratories, Daisy Building, HU16 5JQ Hull, UK.
RP Oguh-Olayinka, L (reprint author), Castle Hill Hospital, Hull York Medical School, Research Laboratories, HU16 5JQ Hull, UK.
EM L.Cawkwell@hull.ac.uk
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 985
EP 995
DI 10.1007/s12253-019-00652-x
PG 11
ER
PT J
AU Kajary, K
Lengyel, Zs
Tokes, AM
Kulka, J
Dank, M
Tokes, T
AF Kajary, Kornelia
Lengyel, Zsolt
Tokes, Anna-Maria
Kulka, Janina
Dank, Magdolna
Tokes, Timea
TI Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Kinetics; PET-CT; Tumor-infiltrating lymphocytes
ID Breast cancer; Kinetics; PET-CT; Tumor-infiltrating lymphocytes
AB Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients’ informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively. To delineate primary tumors we applied a frame-by-frame semi-automatic software-based correction of motion artefacts. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). We found that k3, Ki and MRFDG were significantly higher in higher grade (p = 0.0246, 0.0089 and 0.0076, respectively), progesterone-receptor negative (p = 0.0344, 0.0217 and 0.0132) and highly-proliferating (p = 0.0414, 0.0193 and 0.0271) tumors as well as in triple-negative and hormone-receptor negative/HER2-positive subtypes (p = 0.0310, 0.0280 and 0.0186). Ki and MRFDG were significantly higher in estrogen receptor negative tumors (p = 0.0300 and 0.0247, respectively). Ki was significantly higher in node-positive than in node-negative disease (p = 0.0315). None of the assessed FDG-kinetic parameters showed significant correlation with stromal TIL. In conclusion, we confirmed a significant relationship between kinetic parameters measured by dynamic PET and the routinely assessed clinicopathological factors of breast cancer: high-grade, hormone-receptor negative tumors with high proliferation rate are characterized by higher cellular FDG-uptake and FDG-phosphorylation rate. Furthermore, we found that kinetic parameters based on the dynamic examinations are probably not influenced by stromal TIL infiltration.
C1 [Kajary, Kornelia] Pozitron Diagnosztika Kft, Hunyadi J. Str. 9, H-1117 Budapest, Hungary.
[Lengyel, Zsolt] Pozitron Diagnosztika Kft, Hunyadi J. Str. 9, H-1117 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi str. 93, H-1091 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi str. 93, H-1091 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of Oncology, Tomo utca 25-29, H-1083 Budapest, Hungary.
[Tokes, Timea] Semmelweis University, Department of Oncology, Tomo utca 25-29, H-1083 Budapest, Hungary.
RP Tokes, T (reprint author), Semmelweis University, Department of Oncology, H-1083 Budapest, Hungary.
EM tokes.timea@med.semmelweis-univ.hu;timi.tokes@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 997
EP 1006
DI 10.1007/s12253-019-00641-0
PG 10
ER
PT J
AU Guo, Y
Qiao, X
Zhu, L
Song, R
AF Guo, Yan
Qiao, Xue
Zhu, Li
Song, Rongbo
TI MicroRNA-182-5p Modulates Oral Squamous Cell Carcinoma Migration and Invasion Via Targeting MTSS1 Gene
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; miR-182-5p; MTSS1; Migration; Invasion
ID Oral squamous cell carcinoma; miR-182-5p; MTSS1; Migration; Invasion
AB Oral squamous cell carcinoma (OSCC) characterized with invasive growth, local metastasis and later stage diagnosis was a common malignancy in head and neck region. The aim of this study was to explore the relationship between miR-182-5p and OSCC, which will contribute to find potential biomarker for OSCC metastasis. MiR-182-5p expression level was detected by the quantitative real-time PCR (qRT-PCR). Cell migration and invasion ability were examined by scratch and Transwell assay. Loss of function together with luciferase reporter assay were used to verify the miR-182-5p modulated OSCC cells migration and metastasis was mediated by MTSS1. The expression of MTSS1 protein was examined by western blotting. MiR-182-5p upregulated in OSCC, was involved in the migration and invasion of OSCC and the increased miR-182-5p expression was correlated with lower OSCC differentiation grade, higher T and N stage. Bioinformatics analysis predicted MTSS1 gene was a potential target of miR-182-5p. Following co-transfection, qRT-PCR, luciferase activities assay and western blotting confirmed that MTSS1 gene was a direct target of miR-182-5p and silence of MTSS1 could reverse the effects of miR-182-5p on OSCC migration and invasion. MiR-182-5p was up-regulated in OSCC and the ability of miR-182-5p to promote MTSS1 repression may precipitate in the OSCC through bypassing cell migration and invasion control.
C1 [Guo, Yan] China Medical University, School of Stomatology, Department of Central Laboratory, 117 North Nanjing Street, Heping District, 110002 Shenyang, Liaoning, China.
[Qiao, Xue] China Medical University, School of Stomatology, Department of Central Laboratory, 117 North Nanjing Street, Heping District, 110002 Shenyang, Liaoning, China.
[Zhu, Li] China Medical University, School of Stomatology, Department of Central Laboratory, 117 North Nanjing Street, Heping District, 110002 Shenyang, Liaoning, China.
[Song, Rongbo] China Medical University, School of Stomatology, Department of Central Laboratory, 117 North Nanjing Street, Heping District, 110002 Shenyang, Liaoning, China.
RP Guo, Y (reprint author), China Medical University, School of Stomatology, Department of Central Laboratory, 110002 Shenyang, China.
EM yguo@cmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1007
EP 1013
DI 10.1007/s12253-019-00647-8
PG 7
ER
PT J
AU Shams, R
Seifi-Alan, M
Bandehpour, M
Omrani, DM
Ghafouri-Fard, S
AF Shams, Roshanak
Seifi-Alan, Mahnaz
Bandehpour, Mojgan
Omrani, Davood Mir
Ghafouri-Fard, Soudeh
TI C-X-C Chemokine Receptor Type 7 (CXCR-7) Expression in Invasive Ductal Carcinoma of Breast in Association with Clinicopathological Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CXCR-7; C-X-C chemokine receptor type 7; Breast cancer
ID CXCR-7; C-X-C chemokine receptor type 7; Breast cancer
AB C-X-C chemokine receptor type 7 (CXCR-7) is an atypical receptor for chemokines whose role in different stages of carcinogenesis has been evaluated in breast cancer cell lines and animal models. Moreover, it has been demonstrated to be a target of regulation by the tumor suppressor microRNA (miR)-100. In the present study, we assessed CXCR-7 expression in 60 breast cancer patients in association with clinicopathological and demographic data of patients. We also extracted the results of our previous work on miR-100 expression in the same cohort of patients to assess the correlation between miR-100 and CXCR-7 expression levels. Transcript levels of CXCR-7 were significantly higher in tumoral tissues compared with adjacent non-cancerous tissues (ANCTs) (Tumoral vs. ANCTs: 3.64 ± 1.8 vs. 0.73 ± 1.3, P = 0.000). A significant negative correlation was detected between CXCR-7 protein and miR-100 transcript levels (r = −0.526, P < 0.05). High CXCR-7mRNA levels were significantly associated with tumor size (P = 0.01). Besides, high protein levels were more prevalent in higher TNM stages (P = 0.000). Moreover, high CXCR-7 protein levels were significantly associated with ER (P = 0.005) and PR (P = 0.02) status. The present work provides further evidence for the role of CXCR-7 in breast cancer and proposes the elimination of inhibitory effects of miR-100 on CXCR-7 expression as a mechanism for its up-regulation in breast cancer tissues.
C1 [Shams, Roshanak] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Seifi-Alan, Mahnaz] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Bandehpour, Mojgan] Shahid Beheshti University of Medical Sciences, School of Advanced Technologies in Medicine, Department of BiotechnologyTehran, Iran.
[Omrani, Davood Mir] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Ghafouri-Fard, Soudeh] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
RP Ghafouri-Fard, S (reprint author), Shahid Beheshti University of Medical Sciences, Department of Medical Genetics, Tehran, Iran.
EM s.ghafourifard@sbmu.ac.ir
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1015
EP 1020
DI 10.1007/s12253-019-00649-6
PG 6
ER
PT J
AU Zhou, XY
Liu, H
Ding, ZB
Xi, HP
Wang, GW
AF Zhou, Xiang-Yang
Liu, Hong
Ding, Zheng-Bin
Xi, Hai-Peng
Wang, Guang-Wei
TI lncRNA SNHG16 Exerts Oncogenic Functions in Promoting Proliferation of Glioma Through Suppressing p21
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Long non-coding RNA; SNHG16; p21; Glioma
ID Long non-coding RNA; SNHG16; p21; Glioma
AB Glioma is a malignant brain tumor that accounts for 30% of all brain tumors and 80% of malignant brain tumors. This poor clinical outcome makes the study of molecular mechanisms in glioma as an urgent subject. However, the certain mechanism remains unclear. Long non-coding RNAs (lncRNAs) plays a key role in glioma development and progression. In the present study, we aimed to explore the potential mechanisms of lncRNA SNHG16 in glioma. The levels of lncRNA SNHG16 were qualified in both glioma tissues and cell lines using qRT-PCR assay. The ability of cell proliferation was tested via CCK-8 and colony formation assays. Transfections were performed to knockdown SNHG16 and its target gene p21. The cell cycles and cell apoptosis were evaluated using flow cytometry, and the expression of SNHG16, p21 and apoptosis biomarkers were qualified with qRT-PCR and western blot assays. The expression of SNHG16 were up-regulated in both glioma tissues and cell lines. Knockdown of SNHG16 was associated with poor proliferation, decreased monoclonal formation rates, but increased apoptosis rates, which also caused the high expression of p21. Moreover, p21 could mediate cell proliferation and monoclonal formation, promote cell apoptosis in glioma, which was negatively correlated with lncRNA SNHG16. The molecule mechanism experiments revealed that SNHG16 could not only inhibit the expression of p21 but also suppressed the level of caspase 3 and 9, while promoted cyclinD1 and cyclinB1 expression. lncRNA SNHG16 could promote the cell proliferation and inhibit the apoptosis of glioma through suppressing p21, indicating that lncRNA SNHG16 might be quite vital for the diagnosis and progression of glioma and could even be a novel therapeutic target for glioma.
C1 [Zhou, Xiang-Yang] The First Affiliated Hospital of University of South China, Department of Neurosurgery, No.69, Chuanshan Road, Shigu District, 421001 Hengyang, Hunan Province, China.
[Liu, Hong] The First Affiliated Hospital of University of South China, Department of Neurosurgery, No.69, Chuanshan Road, Shigu District, 421001 Hengyang, Hunan Province, China.
[Ding, Zheng-Bin] The First Affiliated Hospital of University of South China, Department of Neurosurgery, No.69, Chuanshan Road, Shigu District, 421001 Hengyang, Hunan Province, China.
[Xi, Hai-Peng] The First Affiliated Hospital of University of South China, Department of Neurosurgery, No.69, Chuanshan Road, Shigu District, 421001 Hengyang, Hunan Province, China.
[Wang, Guang-Wei] The First Affiliated Hospital of University of South China, Department of Neurosurgery, No.69, Chuanshan Road, Shigu District, 421001 Hengyang, Hunan Province, China.
RP Wang, GW (reprint author), The First Affiliated Hospital of University of South China, Department of Neurosurgery, 421001 Hengyang, China.
EM wangguangwei48@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1021
EP 1028
DI 10.1007/s12253-019-00648-7
PG 8
ER
PT J
AU Liu, H
Zhang, Q
Lou, Q
Zhang, X
Cui, Y
Wang, P
Yang, F
Wu, F
Wang, J
Fan, T
Li, Sh
AF Liu, Hongtao
Zhang, Qing
Lou, Qianqian
Zhang, Xin
Cui, Yunxia
Wang, Panpan
Yang, Fan
Wu, Fan
Wang, Jing
Fan, Tianli
Li, Shenglei
TI Differential Analysis of lncRNA, miRNA and mRNA Expression Profiles and the Prognostic Value of lncRNA in Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Long chain non-coding RNA; MicroRNA; messenger RNA; Differential expression; ceRNA; Esophageal cancer
ID Long chain non-coding RNA; MicroRNA; messenger RNA; Differential expression; ceRNA; Esophageal cancer
AB Integrative central axis of lncRNA-miRNA-mRNA plays pivotal roles in tumor development and progression. However, the regulatory role of lncRNA-miRNA-mRNA in esophageal cancer remains elusive. TCGA database was utilized to investigate the differential expression of lncRNA, miRNA and mRNA in esophageal cancer (ESCA) and normal esophageal tissues, and GEO database was used to further validate the expression profile of key genes. Differential lncRNAs in TCGA database were submitted to Starbase, and lncRNAs related to overall survival were analyzed using Kaplan-Meier and log-rank test. We found 145 lncRNAs, 112 miRNAs and 2000 protein coding mRNAs were differentially expressed in ESCA samples, which were tightly involved in chromosome segregation, extracellular matrix assembly by GO assay, and KEGG assay revealed the correlation of differentially expressed genes with cell cycle, apoptosis and cGMP-PKG signaling pathway. Furthermore, there were 291 nodes in ceRNA network, which consisted of 40 lncRNAs, 28 miRNAs and 233 mRNAs, and formed 677 relations. Furthermore, 6 of 10 lncRNAs in TCGA database were consistent with GEO database, and expressions of 10 mRNAs in TCGA database all exhibited the same tendency with GEO database. Notably, we found 8 lncRNAs (WDFY3-AS2, CASC8, UGDH-AS1, RAP2C-AS1, AC007128.1, AC016205.1, AC092803.2 and AC079949.2) were correlated with overall survival of the patients with ESCA. The key differentially expressed genes participate in the development and progression of ESCA, and thus the elucidation of functions of lncRNA-miRNA-mRNA will provide new novel therapeutic target for the patients with ESCA.
C1 [Liu, Hongtao] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Zhang, Qing] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Lou, Qianqian] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Zhang, Xin] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Cui, Yunxia] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Wang, Panpan] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Yang, Fan] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Wu, Fan] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Wang, Jing] Zhengzhou University, College of Life Sciences, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Fan, Tianli] Zhengzhou University, School of Basic Medicine, Department of Pharmacology, 100 Kexue Road, 450001 Zhengzhou, Henan, China.
[Li, Shenglei] The First Affiliated Hospital of Zhengzhou University, Department of Pathology, 40 Daxue Road, 450052 Zhengzhou, Henan, China.
RP Liu, H (reprint author), Zhengzhou University, College of Life Sciences, 450001 Zhengzhou, China.
EM liuht1230@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1029
EP 1039
DI 10.1007/s12253-019-00655-8
PG 11
ER
PT J
AU Yang, Ch
Huang, D
Ma, C
Ren, J
Fu, L
Cheng, Ch
Li, B
Shi, X
AF Yang, Chenggang
Huang, Di
Ma, Cui
Ren, Jing
Fu, Lina
Cheng, Cheng
Li, Bangling
Shi, Xiaofeng
TI Identification of Pathogenic Genes and Transcription Factors in Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Osteosarcoma; Transcription factors; DEGs; Integrated analysis
ID Osteosarcoma; Transcription factors; DEGs; Integrated analysis
AB Osteosarcoma (OS) is an aggressive malignant tumor of the bones. Our study intended to identify and analyze potential pathogenic genes and upstream regulators for OS. We performed an integrated analysis to identify candidate pathogenic genes of OS by using three Gene Expression Omnibus (GEO) databases (GSE66673, GSE49003 and GSE37552). GO and KEGG enrichment analysis were utilized to predict the functional annotation and potential pathways of differentially expressed genes (DEGs). The OS-specific transcriptional regulatory network was established to study the crucial transcriptional factors (TFs) which target the DEGs in OS. From the three GEO datasets, we identified 759 DEGs between metastasis OS samples and non-metastasis OS samples. After GO and KEGG analysis, ‘cell adhesion’ (FDR = 1.27E-08), ‘protein binding’ (FDR = 1.13E-22), ‘cytoplasm’ (FDR = 5.63E-32) and ‘osteoclast differentiation’ (FDR = 0.000992221) were significantly enriched pathways for DEGs. HSP90AA1 exhibited a highest degree (degree = 32) and was enriched in ‘pathways in cancer’ and ‘signal transduction’. BMP6, regulated by Pax-6, was enriched in the ‘TGF-beta signaling pathway’. We indicated that BMP6 may be downregulated by Pax-6 in the non-metastasis OS samples. The up-regulated HSP90AA1 and down-regulated BMP6 and ‘pathways in cancer’ and ‘signal transduction’ were deduced to be involved in the pathogenesis of OS. The identified biomarkers and biological process in OS may provide foundation for further study.
C1 [Yang, Chenggang] Gu’an Bojian Bio-Technology Co. LTDLangfang, China.
[Huang, Di] Gu’an Bojian Bio-Technology Co. LTDLangfang, China.
[Ma, Cui] Gu’an Bojian Bio-Technology Co. LTDLangfang, China.
[Ren, Jing] Beijing Medintell Bioinformatic Technology Co. LTD, No. 1, Shanyuan Street, Haidian District, 100081 Beijing, China.
[Fu, Lina] Beijing Medintell Bioinformatic Technology Co. LTD, No. 1, Shanyuan Street, Haidian District, 100081 Beijing, China.
[Cheng, Cheng] Beijing Medintell Bioinformatic Technology Co. LTD, No. 1, Shanyuan Street, Haidian District, 100081 Beijing, China.
[Li, Bangling] Jiangnan University, School of biotechnologyWuxi, China.
[Shi, Xiaofeng] Gu’an Bojian Bio-Technology Co. LTDLangfang, China.
RP Shi, X (reprint author), Gu’an Bojian Bio-Technology Co. LTD, Langfang, China.
EM shi.xiaofeng@medintell.com
CR ZhouW, Hao M, Du X, Chen K,Wang G, Yang J, 2014, Advances in targeted therapy for osteosarcoma. Discov Med 17(96):301–307
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Yan H, Zhang B, Fang C, Chen L, 2018, Mir-340 alleviates chemoresistance of osteosarcoma cells by targeting zeb1. Anti- Cancer Drugs:1
Pang Y, Zhao J, Fowdur M, Liu Y,Wu H, HeM, 2018, To explore the mechanism of the grm4 gene in osteosarcoma by rna sequencing and bioinformatics approach. Med Sci Monit Basic Res 24:16– 25
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Diao C, Xi Y, Xiao T, 2018, Identification and analysis of key genes in osteosarcoma using bioinformatics. Oncol Lett 15(3): 2789–2794
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1041
EP 1048
DI 10.1007/s12253-019-00645-w
PG 8
ER
PT J
AU Gasinska, A
Jaszczynski, J
Rychlik, U
Luczynska, E
Pogodzinski, M
Palaczynski, M
AF Gasinska, Anna
Jaszczynski, Janusz
Rychlik, Urszula
Luczynska, Elzbieta
Pogodzinski, Marek
Palaczynski, Mikolaj
TI Prognostic Significance of Serum PSA Level and Telomerase, VEGF and GLUT-1 Protein Expression for the Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostatic carcinoma; Biochemical failure; PSA; GLUT-1; VEGF; hTERT
ID Prostatic carcinoma; Biochemical failure; PSA; GLUT-1; VEGF; hTERT
AB The aim of the study was to evaluate prognosis for biochemical recurrence (BR) by analysing the pathological and biological characteristics of prostate cancer (PCa) after radical prostatectomy (RP). There were 130 men with clinically localized PCa in whom pretreatment serum PSA level and Ki-67, prostate specific membrane antigen (PSMA), glucose transporter-1 (GLUT-1), vascular endothelial growth factor (VEGF), microvessel density (MVD) and human telomerase reverse transcriptase (hTERT) proteins expression, based on number of immunohistochemically positive cells (labelling index), were retrospectively studied. In order to assess the prognostic significance of analysed variables in univariate and multivariate Cox analysis, patients were dichotomized based on cut-off points chosen by receiver operating characteristic (ROC) curves. There were 83 males (63.8%) at pTstage 1–2 and 47 (36.1%) at pTstage 3–4, respectively, with median (range) age of 62.8 years (49–77), and median follow-up of 78.5 months (12–148). In 42 (32.3%) men BR was found. In univariate analysis, tumour biological features: PSA ≤8 ng/ mL (p = 0.006), Ki-67LI ≤ 12.7% (p = 0.015), VEGFLI>11.0% (p = 0.030), and hTERTLI>6.7% (p = 0.016), but not clinicopathological parameters, appeared to be positive prognosticators for BRFS. In the Cox analysis, Ki-67 lost its significance, and clinicopathological parameters appeared to be nonsignificant. The independent negative prognostic factors for BRFS were: PSA > 8.0 ng/mL, (Hazard ratio = 2.75, p = 0.003), GLUT-1 > 19.1% (HR = 2.1, p = 0.032), VEGF≤11.0% (HR = 1, p = 0.024) and hTERT≤6.7% (HR = 1, p = 0.017). High PSA level, and GLUT-1 expression and lower VEGF and nuclear hTERT expression may indicate the great role of hypoxia in BR induction in PCa.
C1 [Gasinska, Anna] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of Tumour Pathology, Garncarska 11, 31-115 Krakow, Poland.
[Jaszczynski, Janusz] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of SurgeryKrakow, Poland.
[Rychlik, Urszula] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of Clinical BiochemistryKrakow, Poland.
[Luczynska, Elzbieta] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of RadiologyKrakow, Poland.
[Pogodzinski, Marek] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of SurgeryKrakow, Poland.
[Palaczynski, Mikolaj] Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of SurgeryKrakow, Poland.
RP Gasinska, A (reprint author), Maria Sklodowska - Curie Institute, Cracow Branch, Oncology Center, Department of Tumour Pathology, 31-115 Krakow, Poland.
EM z5gasins@cyf-kr.edu.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1049
EP 1056
DI 10.1007/s12253-019-00659-4
PG 8
ER
PT J
AU Li, Z
Guo, Z
AF Li, Zhi
Guo, Zhiqiang
TI Comparison of CDH1 Gene Hypermethylation Status in Blood and Serum among Gastric Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Hypermethylation; CDH1 gene; Prognosis
ID Gastric cancer; Hypermethylation; CDH1 gene; Prognosis
AB Hypermethylation is epigenetic alteration, well known for gene silencing. CHD1 gene is known as invasion and tumor suppressor gene, decreased expression due to hypermethylation could promote tumor cell invasion and metastasis. Present study designed to investigate the CDH1 gene promoter hypermethylation status by methylation specific polymerase chain reaction in 100 newly diagnosed gastric cancer patients. 53% of hypermethylation was observed in DNA extracted from blood in Gastric cancer patients while 66% was observed in serum-based DNA. Significant differences in CDH1gene promoter hypermethylation was observed in serum-based DNA extracted from Gastric cancer patients. Patients in early stage (I&II) vs advanced stage (III&IV), distant organ metastases vs no metastases had 60% vs 7% and 42% 24% of CDH1 promoter hypermethylation in serum DNA (p = 0.006, 0.001) respectively. Patients who were with lymph node invasion, loss of appetite, loss of weight had 55%, 47%, 61% CDH1 gene promoter hypermethylation compare to who were not with lymph node invasion, loss of appetite, loss of weight had 11%, 19%, 5% of hypermethylation and these differences was found to be significant. Strong association was observed with overall median survival of patients (p < 0.0001). Patients who had CDH1 gene promoter hypermethylation in serum-based DNA showed poor overall median survival (14.3 months) and unmethylated patients had better overall median survival (33.2 months). CDH1 hypermethylation status was found to be associated with advancement of disease, distant organ metastases and lymph node invasion in Gastric cancer patients.
C1 [Li, Zhi] Lanzhou petrochemical general hospital, Gansu Gem Flower Hospital, Physical examination center, 730060 Lanzhou, Gansu, China.
[Guo, Zhiqiang] Lanzhou petrochemical general hospital, Gansu Gem Flower Hospital, Medical section, 730060 Lanzhou, Gansu, China.
RP Guo, Z (reprint author), Lanzhou petrochemical general hospital, Gansu Gem Flower Hospital, Medical section, 730060 Lanzhou, China.
EM georgiadespori@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1057
EP 1062
DI 10.1007/s12253-019-00658-5
PG 6
ER
PT J
AU Feng, Y
Jiang, Y
Wen, T
Meng, F
Shu, X
AF Feng, Yueyi
Jiang, Yiqing
Wen, Tao
Meng, Fang
Shu, Xiaochen
TI Identifying Potential Prognostic Markers for Muscle-Invasive Bladder Urothelial Carcinoma by Weighted Gene Co-Expression Network Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Muscle-invasive bladder urothelial carcinoma (MIBC); WGCNA; Prognostic marker; Hub gene
ID Muscle-invasive bladder urothelial carcinoma (MIBC); WGCNA; Prognostic marker; Hub gene
AB Muscle-invasive bladder urothelial carcinoma (MIBC) is characterized as a genetic heterogeneous cancer with a high percentage of recurrence and worse prognosis. Identify the prognostic potentials of novel genes for muscle-invasive urothelial bladder cancer could at least provide important information for early detection and clinical treatment. Weighted gene co-expression network analysis (WGCNA) algorithm, a powerful systems biology approach, was utilized to extract co-expressed gene networks from mRNA expression dataset to construct transcriptional modules in MIBC samples, which was associated with demographic and clinical traits of MIBC patients. The potential prognostic markers of MIBC were screened out in the discovery dataset and verified in an independent external validation dataset. A total of 8 co-expression modules were detected through the WGCNA algorithm in the discovery datasets based on 401 MIBC samples. One transcriptional module enriched in cell development was observed to be correlated with the MIBC prognosis in the discovery datasets (HR = 1.48, 95%CI = 1.04–2.11) and independently verified in an external dataset (HR = 3.59, 95%CI = 1.09–11.79). High expression of hub genes including discoidin domain receptor tyrosine kinase 2 (DDR2), PDZ and LIM domain 3 (PDLIM3), zinc finger protein 521 (ZNF521), methionine sulfoxide reductase B3 (MSRB3) were significantly associated with the unfavorable survival of MIBC patients. We identified and validated four novel potential biomarkers associated with prognosis of MIBC patients by constructing genes co-expression networks. The discovery of these genetic markers may provide a new target for the development of MIBC chemotherapeutic drugs.
C1 [Feng, Yueyi] Medical College of Soochow University, School of Public Health, Department of Epidemiology, 215123 Suzhou, China.
[Jiang, Yiqing] Harrison International Peace Hospital, Department of General Surgery, 053000 Hengshui, China.
[Wen, Tao] Capital Medical University, Beijing Chao-Yang Hospital, Medical Research Centre, 100020 Beijing, China.
[Meng, Fang] Chinese Academy of Medical Sciences, Centre of Systems Medicine, 100730 Beijing, China.
[Shu, Xiaochen] Medical College of Soochow University, School of Public Health, Department of Epidemiology, 215123 Suzhou, China.
RP Shu, X (reprint author), Medical College of Soochow University, School of Public Health, Department of Epidemiology, 215123 Suzhou, China.
EM xcshu@suda.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1063
EP 1072
DI 10.1007/s12253-019-00657-6
PG 10
ER
PT J
AU Shousha, S
Anscombe, O
McFarlane, T
AF Shousha, Sami
Anscombe, Oliver
McFarlane, Taneisha
TI All Benign and Malignant Apocrine Breast Lesions Over-Express Claudin 1 and 3 and Are Negative for Claudin 4
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast; Apocrine breast carcinoma; Triple negative carcinoma; Claudin 1; Claudin 3; Claudin 4
ID Breast; Apocrine breast carcinoma; Triple negative carcinoma; Claudin 1; Claudin 3; Claudin 4
AB Invasive apocrine carcinoma of the breast is an uncommon triple negative tumour that lacks a specific therapeutic target. Apocrine metaplasia of the breast shares common morphological features with apocrine carcinoma, and was previously found to consistently over-express claudin 1 and to lack claudin 4. This study was aimed at finding whether apocrine carcinoma, and other related apocrine breast lesions, have similar claudin profile. The immunohistochemical expression of claudin 1, 3 and 4 was studied in 11 cases of in situ and invasive apocrine breast carcinoma, 7 benign apocrine lesions and 45 consecutive morphologically non-apocrine triple negative breast carcinomas. All cases were also immunostained for Gross Cystic Disease Fluid Protein- 15 (GCDFP-15), a marker for apocrine differentiation. Apocrine breast lesions maintained their expression pattern from benign through DCIS to invasive carcinoma; all showing strong expression of claudin 1 and 3 and absence of claudin 4. The same pattern of expression was seen in 2 out of the 45 morphologically non-apocrine tumours, but both showed strong positive staining for GCDFP-15. It is concluded that all benign and malignant apocrine lesions of the breast have a consistent pattern of claudin 1, 3 and 4 expression, suggesting the presence of a specific pathway for the development of invasive apocrine carcinoma. The overexpression of claudin 1 and 3 may have therapeutic implications as targets for managing apocrine cancers.
C1 [Shousha, Sami] Charing Cross Hospital and Imperial College, Department of Histopathology, Fulham Palace Road, W6 8RF London, UK.
[Anscombe, Oliver] Charing Cross Hospital and Imperial College, Department of Histopathology, Fulham Palace Road, W6 8RF London, UK.
[McFarlane, Taneisha] Charing Cross Hospital and Imperial College, Department of Histopathology, Fulham Palace Road, W6 8RF London, UK.
RP Shousha, S (reprint author), Charing Cross Hospital and Imperial College, Department of Histopathology, W6 8RF London, UK.
EM S.shousha@imperial.ac.uk
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1073
EP 1078
DI 10.1007/s12253-019-00662-9
PG 6
ER
PT J
AU Liu, Y
Liang, G
Zhou, T
Liu, Z
AF Liu, Yang
Liang, Guodong
Zhou, Tingting
Liu, Zengshan
TI Silencing UHRF1 Inhibits Cell Proliferation and Promotes Cell Apoptosis in Retinoblastoma Via the PI3K/Akt Signalling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE UHRF1; Retinoblastoma; PI3K/Akt signalling pathway; Cell proliferation; Cell apoptosis
ID UHRF1; Retinoblastoma; PI3K/Akt signalling pathway; Cell proliferation; Cell apoptosis
AB This study aimed to investigate the effect of silencing ubiquitin-like with PHD and RING finger domains 1 (UHRF1) on the proliferation and apoptosis of retinoblastoma (RB) cells and to clarify the molecular mechanism of the UHRF1 gene in the development of RB. Human RBWERI-Rb-1 cells were selected and assigned into a blank group (WERI-Rb-1 cells with no transfection), NC-shRNA group (WERI-Rb-1 cells infected with NC-shRNA virus) and UHRF1-shRNA group (WERI-Rb-1 cells infected with pGC-UHRF1-shRNALV-GFP# (39–1) virus). The mRNA and protein expression of UHRF1 was detected by RT-qPCR and Western blot analysis. The effect of silencing UHRF1 on the proliferation and apoptosis of WERI-Rb-1 cells was assessed by MTT assay, EdU assay, flowcytometry, and Hoechst staining. Furthermore, the expression of cell cycle-related factor (cyclin D1), apoptosis-related factors (caspase-9, Bcl-2 and Bax), and PI3K/Akt signalling pathway-related factors (p-PI3K, PI3K, p-Akt and Akt) were measured via Western blot analysis. The RNA interference plasmid UHRF1-shRNA was successfully constructed. After WERI-Rb-1 cells were infected with UHRF1-shRNA, decreased mRNA and protein expression of UHRF1 was found. WERI-Rb-1 cells infected with UHRF1-shRNA showed inhibited proliferative ability and increased apoptosis. In the UHRF1-shRNA group, more cells arrested at the G0/G1 phase and less cells at the S and G2/M phases. WERI-Rb-1 cells infected with UHRF1-shRNA had increased expression of caspase-9 and Bax and decreased expression of Bcl-2 expression and decreased levels of p-PI3K and p-Akt. In conclusion, our study demonstrated that silencing UHRF1 could inhibit the proliferation of RB cells and promote apoptosis. The mechanism may be caused by the downregulation of the proportion of Bcl-2/Bax expression and the promotion of the expression of caspase-9 through the PI3K/Akt signalling pathway.
C1 [Liu, Yang] Ministry of Education Institutes, Jilin University, College of Veterinary Medicine, Key Laboratory of Zoonosis, No. 5333 Xi’an Road, 130062 Changchun, China.
[Liang, Guodong] Jilin Cancer Hospital, Department of Colorectal and Stomach Cancer Surgery, 130062 Changchun, China.
[Zhou, Tingting] The Affiliated Hospital of Changchun University of Chinese Medicine, 130062 Changchun, China.
[Liu, Zengshan] Ministry of Education Institutes, Jilin University, College of Veterinary Medicine, Key Laboratory of Zoonosis, No. 5333 Xi’an Road, 130062 Changchun, China.
RP Liu, Z (reprint author), Ministry of Education Institutes, Jilin University, College of Veterinary Medicine, Key Laboratory of Zoonosis, 130062 Changchun, China.
EM zengshanliu18@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1079
EP 1088
DI 10.1007/s12253-019-00656-7
PG 10
ER
PT J
AU Boldrini, L
Giordano, M
Melfi, F
Lucchi, M
Fontanini, G
AF Boldrini, Laura
Giordano, Mirella
Melfi, Franca
Lucchi, Marco
Fontanini, Gabriella
TI Distinct Angiogenic microRNA-mRNA Expression Profiles Among Subtypes of Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microRNAs; Angiogenesis; Lung adenocarcinoma subtypes; VEGF
ID microRNAs; Angiogenesis; Lung adenocarcinoma subtypes; VEGF
AB Adenocarcinoma (ADC) represents the most common histological type of non-small cell lung cancer (NSCLC), with a heterogeneous pattern of growth classified as lepidic, acinar, papillary, solid, and micropapillary. For ADC patients there are few available therapeutic options and a valuable therapeutic strategy is represented by angiogenesis inhibitors; however, new reliable biomarkers to identify patients with benefit from anti-angiogenic drugs are needed. We designed a panel of sixteen miRNAs together with six their mRNA targets involved in the angiogenesis pathway and expression analysis was performed by the nCounter System® (NanoString Technologies) in 88 ADC patients: 29 were predominantly lepidic (33%), 26 solid (29.5%), 22 acinar (25%), and for 11 patients the prevalent pattern was papillary (12.5%). When we compared mRNA expression levels with the different histological ADC subtypes we found a significant higher expression of VEGF in papillary and solid than in other subtypes (p = 0.008). Among 16 miRNAs that target the angiogenic mRNA, 4 were significantly downregulated in papillary/solid compared to other groups. Our data suggest a distinct angiogenic miRNA-mRNA expression profile among the subtypes of ADC, with a putative clinical application to stratify patients for anti-angiogenetic drugs. Moreover, the regulation of angiogenic mRNA factors by miRNAs could provide a novel therapeutic approach based on their expression pattern specific for distinct ADC subtypes. Further studies are needed in a larger cohort of patients to confirm our results.
C1 [Boldrini, Laura] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Giordano, Mirella] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Melfi, Franca] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Lucchi, Marco] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
[Fontanini, Gabriella] University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, Via Roma 57, 56126 Pisa, Italy.
RP Boldrini, L (reprint author), University of Pisa, Department of Molecular, Medical and Surgical Pathology and of the Critical Area, 56126 Pisa, Italy.
EM laura.boldrini@med.unipi.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1089
EP 1096
DI 10.1007/s12253-019-00664-7
PG 8
ER
PT J
AU de Araujo, BA
Infanger Serrano, LTh
Mota Pedroso, CM
Mariano, VF
Altemani, A
Gripp, MF
Crespo, NA
Chone, TC
AF de Araujo, Bueno Amanda
Infanger Serrano, Luis Thiago
Mota Pedroso, Claudia Maria
Mariano, Viviane Fernanda
Altemani, Albina
Gripp, Mignone Flavio
Crespo, Nubiato Agricio
Chone, Takahiro Carlos
TI Clinicopathologic Diagnostic and Prognostic Factors of Spindle Cell Carcinoma of Upper Airway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Spindle cell carcinoma; Sarcomatoid carcinoma; Head and neck cancer; Immunohistochemistry; Prognostic factors
ID Spindle cell carcinoma; Sarcomatoid carcinoma; Head and neck cancer; Immunohistochemistry; Prognostic factors
AB Spindle cell carcinoma (SpCC) is a rare tumor, which occurs in upper respiratory tract, mainly in larynx. This study aimed to review the clinical and pathological characteristics for diagnosis and prognosis. Retrospective cohort study. All patients with SpCC in upper respiratory tract treated for curative intent was included. All patients were reviewed in search of epithelial component and immunohistochemistry when not found. It was evaluated rate of recurrence and disease-free survival with univariate and multivariate analysis with Kaplan Meier and Cox Regression model adjusted to propensity score indexes (PSI) according to age, gender, site of tumor, stage, surgical treatment, status of margins of surgical resection, lymphatic invasion. There were 16 cases of SpCC.31% were diagnosed with light microscopy and others with immunohistochemistry for epithelial marker. Disease-free survival was higher in early stage disease in univariate and multivariate analysis, as the main prognostic factor. Surgical treatment increases in 2.54 the rate of survival. The SpCC is a rare tumor considered a highly malignant variant of squamous cell carcinoma. It has male predominance and tobacco use as risk factors. Its treatment should follow the same recommendations for squamous cell carcinoma, with surgery as the maintain treatment. Immunohistochemistry is an adjuvant important tool for diagnosis of SpCC.
C1 [de Araujo, Bueno Amanda] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
[Infanger Serrano, Luis Thiago] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
[Mota Pedroso, Claudia Maria] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
[Mariano, Viviane Fernanda] UNICAMP - University of Campinas, School of Medicine, Department of PathologyCampinas, Sao Paulo, Brazil.
[Altemani, Albina] UNICAMP - University of Campinas, School of Medicine, Department of PathologyCampinas, Sao Paulo, Brazil.
[Gripp, Mignone Flavio] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
[Crespo, Nubiato Agricio] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
[Chone, Takahiro Carlos] University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Sao Paulo, Brazil.
RP de Araujo, BA (reprint author), University of Campinas, UNICAMP, Department of Otorhinolaryngology, Head Neck, 13081-970 Campinas, Brazil.
EM mandibueno@hotmail.com
CR Virchow V. Die Krankhaften Geschwfilste, vol 2. Berlin, Germany: A. Hirschwald; 1864-1865:181-182.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1097
EP 1104
DI 10.1007/s12253-019-00654-9
PG 8
ER
PT J
AU Yeh, YS
Chen, YT
Tsai, HL
Huang, ChW
Ma, ChJ
Su, WCh
Huang, ChM
Huang, MY
Hu, HM
Lu, ChY
Wang, JY
AF Yeh, Yung-Sung
Chen, Yi-Ting
Tsai, Hsiang-Lin
Huang, Ching-Wen
Ma, Cheng-Jen
Su, Wei-Chih
Huang, Chun-Ming
Huang, Ming-Yii
Hu, Huang-Ming
Lu, Chien-Yu
Wang, Jaw-Yuan
TI Predictive Value of ERCC1, ERCC2, and XRCC Expression for Patients with Locally Advanced or Metastatic Gastric Cancer Treated with Neoadjuvant mFOLFOX-4 Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE locally advanced gastric cancer; metastatic gastric cancer; mFOLFOX-4; neoadjuvant; ERCC1; ERCC2
ID locally advanced gastric cancer; metastatic gastric cancer; mFOLFOX-4; neoadjuvant; ERCC1; ERCC2
AB The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.
C1 [Yeh, Yung-Sung] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Trauma and Surgical Critical Care, Department of SurgeryKaohsiung, Taiwan, Republic of China.
[Chen, Yi-Ting] Kaohsiung Medical University, College of Medicine, Department of PathologyKaohsiung, Taiwan, Republic of China.
[Tsai, Hsiang-Lin] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100 Tzyou 1st Road, San-Ming District, 807 Kaohsiung, Taiwan, Republic of China.
[Huang, Ching-Wen] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100 Tzyou 1st Road, San-Ming District, 807 Kaohsiung, Taiwan, Republic of China.
[Ma, Cheng-Jen] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100 Tzyou 1st Road, San-Ming District, 807 Kaohsiung, Taiwan, Republic of China.
[Su, Wei-Chih] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100 Tzyou 1st Road, San-Ming District, 807 Kaohsiung, Taiwan, Republic of China.
[Huang, Chun-Ming] Kaohsiung Medical University, College of Medicine, Graduate Institute of Clinical MedicineKaohsiung, Taiwan, Republic of China.
[Huang, Ming-Yii] Kaohsiung Medical University, Faculty of Medicine, College of Medicine, Department of Radiation OncologyKaohsiung, Taiwan, Republic of China.
[Hu, Huang-Ming] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Gastroenterology, Department of Internal MedicineKaohsiung, Taiwan, Republic of China.
[Lu, Chien-Yu] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Gastroenterology, Department of Internal MedicineKaohsiung, Taiwan, Republic of China.
[Wang, Jaw-Yuan] Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, No. 100 Tzyou 1st Road, San-Ming District, 807 Kaohsiung, Taiwan, Republic of China.
RP Wang, JY (reprint author), Kaohsiung Medical University, Kaohsiung Medical University Hospital, Division of Colorectal Surgery, Department of Surgery, 807 Kaohsiung, Taiwan, Republic of China.
EM cy614112@ms14.hinet.net;jayuwa@cc.kmu.edu.tw
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1105
EP 1116
DI 10.1007/s12253-019-00666-5
PG 12
ER
PT J
AU Szentkereszty, M
Komlosi, IZs
Szucs, G
Barna, G
Tamasi, L
Losonczy, Gy
Galffy, G
AF Szentkereszty, Marton
Komlosi, Istvan Zsolt
Szucs, Gergo
Barna, Gabor
Tamasi, Lilla
Losonczy, Gyorgy
Galffy, Gabriella
TI Effect of COPD on Inflammation, Lymphoid Functions and Progression-Free Survival during First-Line Chemotherapy in Advanced Non-small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Advanced NSCLC; COPD; Inflammation; Lymphopenia; VEGF; MDSC; Neutrophils; CRP; T cell exhaustion
ID Advanced NSCLC; COPD; Inflammation; Lymphopenia; VEGF; MDSC; Neutrophils; CRP; T cell exhaustion
AB Chronic obstructive pulmonary disease (COPD) is a common comorbidity of non-small cell lung cancer (NSCLC). COPD is characterized by systemic inflammation and lymphocyte dysfunction, mechanisms that are also known to accelerate progression of advanced (IIIB-IV) stage NSCLC. We aimed to find out whether COPD exerts an influence on tumor induced inflammatory and lymphoid responses and progression-free survival (PFS) after first-line treatment in advanced NSCLC. Patients suffering from NSCLC (n = 95), COPD (n = 54), NSCLC+COPD (n = 80) and healthy controls (n = 60) were included. PFS, neutrophil granulocyte and lymphocyte cell counts were recorded. Serum IFNγ, TNFα, VEGF concentrations were measured by using multiplex cytometric bead-based immunoassay. Prevalence of myeloid-derived suppressor cell populations (MDSC-s), and signs of T cell exhaustion were tested by using flow cytometry. Median PFS increased in the NSCLC+COPD group compared to NSCLC patients without COPD (7.4 vs 4.9 months, p < 0.01). NSCLC+COPD patients had 1.7 times (1.2–2.4) more likely to have longer PFS compared to NSCLC patients without COPD (Cox analysis, p<0.01). Neutrophil cell counts, CRP, IFNγ and TNFα concentrations were all reduced in NSCLC+COPD (all p < 0.05 vs NSCLC). NSCLC+COPD was also associated with reduced serum IL-10 concentration and increased granzyme-B positive CD8 cell counts compared to NSCLC without COPD. The effects of VEGF and MDSC-s on systemic inflammation appeared to be blunted by COPD in patients suffering from advanced NSCLC. Concomitant COPD moderates tumor-induced inflammation and supports some effector lymphoid functions and thereby may be an independent positive predictive factor of longer PFS after first-line therapy in advanced NSCLC.
C1 [Szentkereszty, Marton] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
[Komlosi, Istvan Zsolt] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
[Szucs, Gergo] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
[Losonczy, Gyorgy] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
[Galffy, Gabriella] Semmelweis University, Department of Pulmonology, Dios arok 1/C, H-1121 Budapest, Hungary.
RP Losonczy, Gy (reprint author), Semmelweis University, Department of Pulmonology, H-1121 Budapest, Hungary.
EM losonczygyrgy@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1117
EP 1128
DI 10.1007/s12253-019-00661-w
PG 12
ER
PT J
AU Hegedus, A
Trzaskoma, L
Soldos, P
Tuza, K
Katona, P
Greger, Zs
Zsarnoczky-Dulhazi, F
Kopper, B
AF Hegedus, Adam
Trzaskoma, Lukasz
Soldos, Peter
Tuza, Kornelia
Katona, Peter
Greger, Zsolt
Zsarnoczky-Dulhazi, Fanni
Kopper, Bence
TI Adaptation of Fatigue Affected Changes in Muscle EMG Frequency Characteristics for the Determination of Training Load in Physical Therapy for Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer treatment; physical rehabilitation; neuromuscular fatigue; Isometric; Motor unit activation
ID Cancer treatment; physical rehabilitation; neuromuscular fatigue; Isometric; Motor unit activation
AB Cancer patients often experience loss in body weight and also a decrease in muscle mass, which results in the reduction of physical activity and mobilization of the patient. To decelerate the loss of muscle mass, as part of the cancer treatment patients frequently undergo physical therapy and considering the physical capabilities of the patients, with moderate loads. Moreover, frequent studies also observed for cancer patients, together with the decrease in muscle mass a shift into fast-twitch muscle fibers from slow-twitch fibers. The aim of our study therefore was to determine how motor fibers behave under moderate isometric load executed until total exhaustion. 11 university students (G1), and 14 elite athletes (G2) participated in the study. 65% of the maximal voluntary contraction (MVC) was determined for the biceps brachii muscle, and with this load holding a weight, participants had to sustain a 90 deg. isometric elbow flexion in a standing posture until complete fatigue occurred. EMG activity for the biceps brachii muscle was measured and frequency analysis was performed. 3 windows were determined in the fatiguing protocol: the first (W1), middle (W2), and last (W3) 5 s, and also frequency analysis for MVC was performed (MAX) between 0 and 260 Hz with 20Hz wide frequency bands. The results indicate, that as the protocol progressed in time and the effect of fatigue increased (from W1 to W3) the activity of low frequency muscle fibers significantly increased (0-40 Hz) while activity of high frequency muscle fibers (60-260 Hz) significantly decreased for G1 and G2 groups identically. We can conclude, that training applied with constant moderate tension as fatigue increases will result in the increased activation of the lower frequency slow– twitch muscle fibers, but the increase of fatigue in the lower frequency fibers will not result in the increase in the activation level of the higher frequency fast-twitch fibers. Consequently, because as slow-twitch fibers are being used at moderate loads and even when fatigue occurs in these fibers the fast-twitch fibers will not work, higher muscle loads are needed if the aim is to activate fast-twitch fibers. Considering the shift into fast-twitch muscle fibers from slow-twitch fibers for cancer patients, in some cases if the patient’s age and physical status allows during the physical treatment, higher loads and consequently higher levels of activation might be beneficial for the retardment of loss concerning the fast-twitch fiber mass.
C1 [Hegedus, Adam] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Trzaskoma, Lukasz] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Soldos, Peter] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Tuza, Kornelia] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Katona, Peter] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Greger, Zsolt] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Zsarnoczky-Dulhazi, Fanni] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Kopper, Bence] University of Physical Education, Department of KinesiologyBudapest, Hungary.
RP Kopper, B (reprint author), University of Physical Education, Department of Kinesiology, Budapest, Hungary.
EM kopper.tf@gmail.com
CR Muscaritoli M, Molfino A, Gioia G, Laviano A, Rossi Fanelli F, 2011, The "parallel pathway": a novel nutritional and metabolic approach to cancer patients. Intern Emerg Med 6(2):105–112
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P,Walsh D,Wilcock A, Kaasa S, Baracos VE, 2011, Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5): 489–495
Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB, 2009, Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15(8):2920–2926
Tisdale MJ, 2010, Cancer cachexia. Curr Opin Gastroenterol 26(2): 146–151
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1129
EP 1135
DI 10.1007/s12253-019-00668-3
PG 7
ER
PT J
AU Zhang, L
Ren, HW
Wu, QL
Wu, YJ
Song, X
AF Zhang, Lei
Ren, Hong-Wei
Wu, Qi-Long
Wu, Yan-Juan
Song, Xiang
TI The Effect of Next-Generation TKI in Non-Small Cell Lung Cancer after Failure of First-Line Treatment: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NSCLC; EGFR-TKIs; Pretreated patients; Meta-analysis
ID NSCLC; EGFR-TKIs; Pretreated patients; Meta-analysis
AB Resistance develops against first-generation tyrosine kinase inhibitors (TKIs), which target the epidermal growth factor receptor (EGFR), after a while for non-small-cell lung cancer (NSCLC). Recently, researchers have developed specific inhibitors against them. Among those inhibitors, next-generation EGFR-TKIs have gained prominence due to the greater efficacy and more favorable tolerability. Today, the efficacy of next-generation EGFR-TKIs in patients with advanced NSCLC after failure on first-generation EGFR-TKIs still remains under investigation. The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation EGFR-TKIs in advanced NSCLC after failure on first-generation EGFR-TKIs. We performed a comprehensive search of the several electronic databases to September, 2018 to identify clinical trials. The primary endpoint was overall survival (OS), progression-free survival (PFS), disease controlled rate (DCR), objective response rate (ORR), and adverse events (AEs). Severe adverse events (AEs) (grade ≥ 3) based on the EGFR-TKIs were analysed. Odds Ratio (OR) along with 95% confidence interval (95% CI) were utilized for the main outcome analysis. In total, we had 3 randomized controlled trials in this analysis. The group of next-generation EGFR-TKIs was significantly improved PFS (OR = 0.34,95%CI = 0.29–0.40, P < 0.00001), as well with the ORR (OR = 10.48,95%CI = 3.87–28.34, P < 0.00001) and DCR (OR = 6.03,95%CI = 4.41–8.25, P < 0.00001), respectively. However, there is no significant difference in overall survival with next-generation EGFR-TKIs (OR = 1.05,95%CI = 0.85–1.31, P = 0.66). While, the OR for the treatment-related AEs of grade 3 or 4 (diarrhoea, rash/acne, nausea, vomiting, anemia) between the patients who received next-generation EGFR-TKIs and chemotherapy did not show safety benefit (P>0.05). Next-generation EGFR-TKIs was shown to be the better agent to achieve higher response rate and the longer PFS in NSCLC patients as the later-line therapy for previously treated patients with first generation EGFR-TKIs. While, the benefit of the OS and safety compared with the chemotherapy did not achieved. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.
C1 [Zhang, Lei] The Second Hospital of Shanxi Medical University, Department of Oncology, No. 382 Wuyi Road, Xinghualing District, 030013 Taiyuan, Shanxi, China.
[Ren, Hong-Wei] The Second Hospital of Shanxi Medical University, Department of Oncology, No. 382 Wuyi Road, Xinghualing District, 030013 Taiyuan, Shanxi, China.
[Wu, Qi-Long] The Second Hospital of Shanxi Medical University, Department of Oncology, No. 382 Wuyi Road, Xinghualing District, 030013 Taiyuan, Shanxi, China.
[Wu, Yan-Juan] The Second Hospital of Shanxi Medical University, Department of Cardio-Thoracic SurgeryTaiyuan, Shanxi, China.
[Song, Xiang] The Second Hospital of Shanxi Medical University, Department of Oncology, No. 382 Wuyi Road, Xinghualing District, 030013 Taiyuan, Shanxi, China.
RP Song, X (reprint author), The Second Hospital of Shanxi Medical University, Department of Oncology, 030013 Taiyuan, China.
EM zhanglei790114@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1137
EP 1143
DI 10.1007/s12253-019-00669-2
PG 7
ER
PT J
AU Celik, B
Bulut, T
Yalcin, DA
AF Celik, Betul
Bulut, Tangul
Yalcin, Didem Arzu
TI Tissue HE4 Expression Discriminates the Ovarian Serous Carcinoma but Not the Uterine Serous Carcinoma Patients. A New Adjunct to the Origin of the Tumor Site
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HE4; Serous; Carcinoma; Ovary; Endometrium; HER2
ID HE4; Serous; Carcinoma; Ovary; Endometrium; HER2
AB Both uterine serous carcinoma (USC) and ovarian serous carcinoma (OSC) are presented at advanced stage at the first admission and disseminated disease makes the anatomical site of the tumor origin impossible. CA125 and p53 are reliable markers that are useful for differentiating both uterine serous and ovarian serous carcinoma from their most common subtypes (endometrioid type carcinoma of ovary and uterus) but so far there is no histopathologic marker that differentiates USC from OSC. On the other hand, Trastuzumab (Herceptin) increases progression-free survival among USC patients, but not OSC patients and makes the histopathologically assigning the origin of the tumor important. So, the aim of this study was to evaluate the immunohistopathological discriminative value of the human epididymis secretory protein 4 (HE4) between OSC and USC patients. Patients with a diagnosis of OSC and UTC were enrolled. HE4 expression was evaluated by immunohistochemistry. The results were compared between groups. Of the tumor tissues studied, HE4 immunostaining was seen in the majority of ovarian serous carcinoma cases (89.65%), while endometrial serous carcinoma cases were devoid of HE4 immunostaining. HE4 immunostaining was seen in 39.1% uterine serous carcinoma cases and this difference was statistically significant (p = 0.001). Our study demonstrated for the first time the potential of HE4 expression to predict the anatomical site of tumor origin. HE4 is a novel tumor marker that differentiates USC from OSC.
C1 [Celik, Betul] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Bulut, Tangul] Antalya Training and Research Hospital, Department of PathologyAntalya, Turkey.
[Yalcin, Didem Arzu] Health Science University, Antalya Hospital, Immunology UnitAntalya, Turkey.
RP Celik, B (reprint author), Antalya Training and Research Hospital, Department of Pathology, Antalya, Turkey.
EM bet_celik@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1145
EP 1151
DI 10.1007/s12253-019-00675-4
PG 7
ER
PT J
AU Ren, ZQ
Yan, WJ
Zhang, XZ
Zhang, Pb
Zhang, Ch
Chen, ShK
AF Ren, Ze-Qiang
Yan, Wen-Jing
Zhang, Xiu-Zhong
Zhang, Peng-bo
Zhang, Chong
Chen, Shou-Kun
TI CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CUL1; Breast Cancer; Epithelial-mesenchymal transition; Akt; GSK3β; EGFR
ID CUL1; Breast Cancer; Epithelial-mesenchymal transition; Akt; GSK3β; EGFR
AB Cullin-1 (CUL1) is an important factor for tumor growth and a potential therapeutic target for breast cancer therapy, but the molecular mechanism in triple-negative breast cancer (TNBC) is unknown. In the present study, CUL1 shRNA was transfected into BT549 and MDA-MB-231 breast cancer cells. Cell morphology, adhesion, invasion, and migration assays were carried out in the CUL1 knockdown cells. Additionally, protein expression levels of epithelial-mesenchymal transition (EMT)-related factors, Akt phosphorylation at S473 (pAkt), glycogen synthase kinase-3β phosphorylation at ser9 (pGSK3β), cytoplasmic and nuclear β-catenin, and epidermal growth factor receptor phosphorylation at Tyr1068 (pEGFR) were detected by Western blot analysis. CUL1 knockdown significantly suppressed the adhesion, invasion and migration capabilities of the cells, and decreased the expression of Snail1/2, ZEB1/2, Twist1/2, Vimentin, and increased the expression of Cytokeratin 18 (CK18). Moreover, CUL1 knockdown significantly downregulated the phosphorylated levels of Akt, GSK3β, and EGFR, inhibiting the translocation of β-catenin from the cytoplasm to the nucleus. The results indicate that CUL1 knockdown prohibited the metastasis behaviors of breast cancer cells through downregulation (dephosphorylation) of the EMT signaling pathways of EGFR and Akt/GSK3β/β-catenin in breast cancer. These results strongly suggested that reinforcement of the EMT might be a key for CUL1 to accelerate TNBC metastasis.
C1 [Ren, Ze-Qiang] Affiliated Hospital of Xuzhou Medical University, General Surgery, 99 West Huaihai Road, 221006 Xuzhou, China.
[Yan, Wen-Jing] Xuzhou Medical University, School of Nursing, 209 Tongshan Road, 221004 Xuzhou, China.
[Zhang, Xiu-Zhong] Affiliated Hospital of Xuzhou Medical University, General Surgery, 99 West Huaihai Road, 221006 Xuzhou, China.
[Zhang, Peng-bo] Affiliated Hospital of Xuzhou Medical University, General Surgery, 99 West Huaihai Road, 221006 Xuzhou, China.
[Zhang, Chong] Affiliated Hospital of Xuzhou Medical University, General Surgery, 99 West Huaihai Road, 221006 Xuzhou, China.
[Chen, Shou-Kun] Affiliated Hospital of Xuzhou Medical University, General Surgery, 99 West Huaihai Road, 221006 Xuzhou, China.
RP Ren, ZQ (reprint author), Affiliated Hospital of Xuzhou Medical University, General Surgery, 221006 Xuzhou, China.
EM rzq0805@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1153
EP 1163
DI 10.1007/s12253-019-00681-6
PG 11
ER
PT J
AU Jaberie, H
Hosseini, VS
Naghibalhossaini, F
AF Jaberie, Hajar
Hosseini, Vahid Seyed
Naghibalhossaini, Fakhraddin
TI Evaluation of Alpha 1-Antitrypsin for the Early Diagnosis of Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Alpha 1-antitrypsin; Colorectal Cancer; CEA; Promoter methylation
ID Alpha 1-antitrypsin; Colorectal Cancer; CEA; Promoter methylation
AB Previous proteomic studies have identified alpha 1-antitrypsin (A1AT) as a potential serum biomarker for colorectal cancer (CRC). In this case-control study, we evaluated plasma A1AT concentration and activity as a biomarker for the early diagnosis of colorectal cancer in a group of 113 sporadic CRC patients. We also analyzed A1AT gene promoter methylation, and genotypes in this group of CRC patients. The plasma A1AT and CEA concentrations were measured using the nephelometric and ELISA methods, respectively. A1AT activity was determined by Trypsin Inhibitor Capacity assay. The genomic DNA from blood samples were subjected to Z and S genotype analysis using PCR-RFLP method and the gene promoter methylation in tumors and their adjacent normal tissues was determined by methylation specific-PCR assay. The plasma levels of A1AT and CEA in patients (median, 2.3 g/L and 5.96 ng/ml, respectively) were significantly higher than those in healthy controls (medians, 1.43 g/L and 2.57 ng/ml, respectively) (p = 0.0001). The plasma A1AT activity and concentrations were positively correlated with the tumor stage and well-discriminated between early and advanced stages. The A1AT activity in plasma was the most useful marker for CRC diagnosis (median 4.8 mmol/min/ml in cases vs 1.91 mmol/min/ml in controls, p = 0.0001). No deficient Z or S alleles of A1AT was observed in patients’ genotype and the gene promoter tends to be more methylated in normal mucosa than in tumor tissues. We conclude that plasma A1AT activity has better sensitivity and specificity than CEA measurement for the early detection of CRC. Promoter demethylation might play a role in increasing plasma A1AT levels in CRC patients.
C1 [Jaberie, Hajar] Shiraz University of Medical Sciences, Department of Biochemistry, Zand Street, 7134845794 Shiraz, Iran.
[Hosseini, Vahid Seyed] Shiraz University of Medical Sciences, Colorectal Research CenterShiraz, Iran.
[Naghibalhossaini, Fakhraddin] Shiraz University of Medical Sciences, Department of Biochemistry, Zand Street, 7134845794 Shiraz, Iran.
RP Naghibalhossaini, F (reprint author), Shiraz University of Medical Sciences, Department of Biochemistry, 7134845794 Shiraz, Iran.
EM fakhraddin.naghibalhossaini@mail.mcgill.ca
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1165
EP 1173
DI 10.1007/s12253-019-00679-0
PG 9
ER
PT J
AU Alsaegh, AM
Altaie, MA
Zhu, Sh
AF Alsaegh, Amjed Mohammed
Altaie, Muayad Alaa
Zhu, Shengrong
TI p63 Expression and its Relation to Epithelial Cells Proliferation in Dentigerous Cyst, Odontogenic Keratocyst, and Ameloblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p63; Ki-67; Odontogenic; Dentigerous; Keratocyst; Ameloblastoma
ID p63; Ki-67; Odontogenic; Dentigerous; Keratocyst; Ameloblastoma
AB The current controversy about the classification of odontogenic keratocyst reflects the shortage in the understanding of the odontogenic cysts and tumors. The aim of the present study was to investigate p63 immunoexpression and its relation to the proliferation of the epithelial lining in dentigerous cyst (DC), odontogenic keratocyst (OKC), and follicular type of ameloblastoma (AB). The study involved 36 samples, which are DC (n = 12), OKC (n=9), and AB (n = 15). p63 protein expression was evaluated by immunohistochemistry. The results on Ki-67 expression were obtained from our previous studies and correlated with p63 expressions. p63 was expressed differently in the studied lesions with various distribution in different study samples. Statistical analysis using Kruskal-Wallis test showed a significant difference in the expression of p63 protein among DC, OKC, and AB (p = 0.048). Subsequently, Mann- Whitney U test revealed the expression of p63 protein was significantly higher in OKC than DC (p = 0.018). Interestingly, Spearman’s correlation analysis showed a positive correlation between the expression of p63 and Ki-67 in the odontogenic epithelium of DC (σ = 0.757, P = 0.004) and OKC (σ=0.741, P = 0.022).While no such a positive correlation was found between the two studied markers in AB group (σ = 0.006, P = 0.983). In conclusion, the present results indicated various expression and correlation of p63 with the proliferation of odontogenic epithelial cells in DC, OKC, and AB. This diversity could reflect a different role and pathways of ΔNp63 in odontogenic tumor than that in odontogenic cyst. These together will help in better understanding the pathogenesis and biological behavior of odontogenic cysts and tumors.
C1 [Alsaegh, Amjed Mohammed] University of Science and Technology of Fujairah, College of Dentistry, Department of Oral and Maxillofacial Surgery, Al-Hulifat, 2202 Fujairah, United Arab Emirates.
[Altaie, Muayad Alaa] Sharjah University, Medical College, Sharjah Medical Research InstituteSharjah, United Arab Emirates.
[Zhu, Shengrong] Huazhong University of Science and Technology, Tongji Hospital of Tongji Medical College, Department of Oral and Maxillofacial Surgery, 430030 Wuhan, Hubei, China.
RP Alsaegh, AM (reprint author), University of Science and Technology of Fujairah, College of Dentistry, Department of Oral and Maxillofacial Surgery, 2202 Fujairah, United Arab Emirates.
EM mohammedalsaegh@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1175
EP 1182
DI 10.1007/s12253-019-00680-7
PG 8
ER
PT J
AU Zaky, HA
Elsers, D
Bakry, R
Abdelwanis, M
Nabih, O
Hafez, R
Rezk, M
AF Zaky, H Amen
Elsers, Dalia
Bakry, Rania
Abdelwanis, Mostafa
Nabih, Ola
Hafez, Rania
Rezk, Mahmoud
TI Prognostic Value of Accumulative Expression of COX-2 and p53 in Small and Diffuse Large B Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE p53; COX-2; Lymphoma
ID p53; COX-2; Lymphoma
AB Cyclooxygenase-2 (COX-2) plays an important role in carcinogenesis, which catalyzes the conversion of arachidonic acid into prostaglandins. P53 is a tumor suppressor gene that contributes to apoptosis and cell cycle control. There is functional interaction between p53 and COX-2, which lead to abrogation of apoptosis and progression of malignancy. To assess the relationship between COX-2, p53 expression and the clinicopathologic features in SLL and DLBCL. We immunohistochemically examined the expression of COX-2 and p53 in non-neoplastic lymphoid cells, lymph nodal low-grade (50 cases of SLL), intermediate and high-grade lymphomas (100 cases of DLBCL) and their corresponding bone marrow specimens. The expression of COX-2 and p53 was absent in the in non-neoplastic lymphoid cells. In contrast, their expression values increased progressively with the advancing grade of lymphoma (p < 0.001). COX-2 expression was significantly associated with advanced disease stage, high grade lymphomas, and disease relapse and p53 expression. The p53was detected in 64.5% in patients positive for COX-2. The expressions of COX-2 and p53 proteins, were significantly associated with shorter overall-survival and progression free survival. Here we report up-regulation of COX-2and p53 protein expression in SLL and DLBCL indicating their interactive involvement in the pathogenesis of lymphoma. Our data provide a rationale for further investigation of COX-2 expression in lymphomas for potential prognostic, chemopreventive and chemotherapeutic purposes.
C1 [Zaky, H Amen] Asyut University, South Egypt Cancer Institute, Medical Oncology & Hematology DepartmentAssiut, Egypt.
[Elsers, Dalia] Asyut University, Faculty of Medicine, Pathology DepartmentAssiut, Egypt.
[Bakry, Rania] Asyut University, South Egypt Cancer Institute, Clinical Pathology DepartmentAssiut, Egypt.
[Abdelwanis, Mostafa] Asyut University, South Egypt Cancer Institute, Radiotherapy DepartmentAssiut, Egypt.
[Nabih, Ola] Asyut University, Clinical Oncology DepartmentAssiut, Egypt.
[Hafez, Rania] Asyut University, Internal Medicine, Hematology UnitAssiut, Egypt.
[Rezk, Mahmoud] Asyut University, Faculty of Medicine, Pathology DepartmentAssiut, Egypt.
RP Zaky, HA (reprint author), Asyut University, South Egypt Cancer Institute, Medical Oncology & Hematology Department, Assiut, Egypt.
EM amenzaky74@yahoo.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1183
EP 1190
DI 10.1007/s12253-019-00674-5
PG 8
ER
PT J
AU Ekalaksananan, T
Wongjampa, W
Phusingha, P
Chuerduangphui, J
Vatanasapt, P
Promthet, S
Patarapadungkit, N
Pientong, Ch
AF Ekalaksananan, Tipaya
Wongjampa, Weerayut
Phusingha, Pensiri
Chuerduangphui, Jureeporn
Vatanasapt, Patravoot
Promthet, Supannee
Patarapadungkit, Natcha
Pientong, Chamsai
TI Comprehensive Data of P53 R282 Gene Mutation with Human Papillomaviruses (HPV)-Associated Oral Squamous Cell Carcinoma (OSCC)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Human papillomavirus; HPV; P53mutation; P53 exon 8 codon 282; Oral squamous cell carcinoma; OSCC; Allele specific oligonucleotide; ASO
ID Human papillomavirus; HPV; P53mutation; P53 exon 8 codon 282; Oral squamous cell carcinoma; OSCC; Allele specific oligonucleotide; ASO
AB Alterations of the P53 gene and human papillomavirus (HPV) infection are associated with development of oral squamous cell carcinoma (OSCC). We aimed to identify mutation of P53 exon 8 codon 282 in OSCC and correlate these with HPV infection as well as histopathological grade of OSCC. Samples of known HPV infection status were studied including oral lesion cells, formalin-fixed paraffin embedded (FFPE) tissues from OSCC and exfoliated oral cells of matched age-sex controls. P53 exon 8 mutation was detected using the polymerase chain reaction (PCR). Mutation of codon 282 was identified by allele-specific oligonucleotide typing (ASO) using EvaGreen real-time PCR. The PCR products were analyzed by gel electrophoresis and melting curve analysis. Mutation of P53 exon 8 was seen in 81.7% and 69.6% of FFPE OSCC tissues and oral lesion cells, respectively. This was significantly higher than in controls (16.7%). Frequency of mutation did not differ between HPV-positive samples (62.5% and 81.8% in oral lesion cells and FFPE tissue samples, respectively) and HPV-negative samples (73.3% and 81.5% in oral lesion cells and FFPE tissue samples, respectively). This finding is similar to P53 codon 282 mutation that was found only in FFPE tissues (35.0%) and oral lesion cells (32.6%) from both HPV-positive and negative OSCC. Interestingly, frequency of mutation was higher in well-differentiated OSCC with HPV-infection (28.1%) than without HPV (14.8%). This result demonstrated a mutation hot spot in P53 associated with oral carcinogenesis and might be useful to guide chemotherapeutic modality for HPV-associated OSCC in northeast Thailand.
C1 [Ekalaksananan, Tipaya] Khon Kaen University, Faculty of Medicine, Department of MicrobiologyKhon Kaen, Thailand.
[Wongjampa, Weerayut] Khon Kaen University, Faculty of Medicine, Department of MicrobiologyKhon Kaen, Thailand.
[Phusingha, Pensiri] Khon Kaen University, Faculty of Medicine, Department of MicrobiologyKhon Kaen, Thailand.
[Chuerduangphui, Jureeporn] Khon Kaen University, Faculty of Medicine, Department of MicrobiologyKhon Kaen, Thailand.
[Vatanasapt, Patravoot] Khon Kaen University, HPV & EBV and Carcinogenesis Research GroupKhon Kaen, Thailand.
[Promthet, Supannee] Khon Kaen University, HPV & EBV and Carcinogenesis Research GroupKhon Kaen, Thailand.
[Patarapadungkit, Natcha] Khon Kaen University, HPV & EBV and Carcinogenesis Research GroupKhon Kaen, Thailand.
[Pientong, Chamsai] Khon Kaen University, Faculty of Medicine, Department of MicrobiologyKhon Kaen, Thailand.
RP Pientong, Ch (reprint author), Khon Kaen University, Faculty of Medicine, Department of Microbiology, Khon Kaen, Thailand.
EM chapie@kku.ac.th
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1191
EP 1199
DI 10.1007/s12253-019-00673-6
PG 9
ER
PT J
AU Zhang, W
Liu, M
Li, Y
Song, Sh
Li, K
Ma, Y
AF Zhang, Wei
Liu, Mingkai
Li, Yue
Song, Shichao
Li, Kai
Ma, Yongliang
TI The Role of O6-methylguanine-DNA Methyltransferase Polymorphisms in Prostate Cancer Susceptibility: a Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MGMT; PCa; Prostate cancer; Risk; Meta-analysis
ID MGMT; PCa; Prostate cancer; Risk; Meta-analysis
AB To assess the associations between O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms and prostate cancer risk. We retrieved PubMed, Cochrane Library and Embase electronic database to search for all eligible studies published from Jan 1, 1970 to Sep 31, 2017 to conduct a Meta-analysis. We identified 11 independent studies in 5 eligible reports, including 5143 cases and 8118 controls. The data suggested that rs12917 was associated with higher PCa risk under the contrast of TT vs CC and recessive model in overall population (TT vs CC: OR = 1.599, 95%CI: 1.007–2.539, P = 0.047; TT vs CC + CT: OR = 1.627, 95%CI: 1.026–2.580, P = 0.038). In subgroup analyses stratified by ethnicity, the remarkable association with higher PCa risk was detected under allelic model, dominant model, the contrast of TC vs CC, and the contrast of TC vs CC + TT in Asian population. (T vs C: OR = 1.911, 95%CI: 1.182–3.090, P = 0.008; TC vs CC: OR = 1.948, 95%CI: 1.152–3.295, P = 0.013; TC + TT vs CC: OR = 1.994, 95%CI: 1.190–3.342, P = 0.009; TC vs CC + TT: OR = 1.926, 95%CI: 1.140–3.255, P = 0.014). However, the data suggest the rs2308327 and rs2308321 polymorphisms of the MGMT gene were nor associated with the susceptibility of prostate cancer. Based on the meta-analysis, MGMT rs12917 polymorphism increase the susceptibility to prostate cancer, which can be taken for a diagnosis and screening molecular biomarker for prostate cancer patients.
C1 [Zhang, Wei] Affiliated Hospital of Hebei University, Department of Urology, 071000 Baoding, China.
[Liu, Mingkai] Affiliated Hospital of Hebei University, Department of Urology, 071000 Baoding, China.
[Li, Yue] Affiliated Hospital of Hebei University, Department of Urology, 071000 Baoding, China.
[Song, Shichao] Affiliated Hospital of Hebei University, Department of Urology, 071000 Baoding, China.
[Li, Kai] Affiliated Hospital of Hebei University, Department of Urology, 071000 Baoding, China.
[Ma, Yongliang] Fourth Hospital of Hebei Medical University, Department of Urology, 050011 Shijiazhuang, China.
RP Ma, Y (reprint author), Fourth Hospital of Hebei Medical University, Department of Urology, 050011 Shijiazhuang, China.
EM 284569670@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1201
EP 1209
DI 10.1007/s12253-019-00672-7
PG 9
ER
PT J
AU Stec, R
Cierniak, Sz
Lubas, A
Brzoskowska, U
Syrylo, T
Zielinski, H
Semeniuk-Wojtas, A
AF Stec, Rafal
Cierniak, Szczepan
Lubas, Arkadiusz
Brzoskowska, Urszula
Syrylo, Tomasz
Zielinski, Henryk
Semeniuk-Wojtas, Aleksandra
TI Intensity of Nuclear Staining for Ki-67, p53 and Survivin as a New Prognostic Factor in Non-muscle Invasive Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; NMIBC; Ki-67; p53; Survivin
ID Bladder cancer; NMIBC; Ki-67; p53; Survivin
AB The aim of the study was to determine the prognostic value of expression levels of biomarkers selected on the basis of the literature: p53, Ki-67, survivin, β-catenin, E-cadherin and N-cadherin in patients with non-muscle invasive bladder cancer. Immunohistochemistry was performed on sections of primary papillary carcinoma of the bladder removed during transurethral resection of the tumor in 134 patients. The expression of β-catenin and E-cadherin was found in all analyzed cases and Ncadherin expression was demonstrated in 3.73% of the tissues examined. The expression of the p53 protein was confirmed in 96.27% of tissues examined. The expression of the Ki-67 protein was demonstrated in all analyzed cases. Survivin expression was found in 95.52% of the study group. Multivariate analysis confirmed the relationship between the recurrence-free survival (RFS) and the intensity of the nuclear reaction for p53 (HR 1417, 95% CI 1.001–2.007, p = 0.049) and survivin (HR 1.451; 95% CI 1.078–1.955; p = 0.014), the expression level of the Ki-67 protein expressed by the TS index (HR 1.146, 95%CI 1.116–1.823, p = 0.005) and the use of adjuvant BCG therapy (HR 0.218, 95% CI 0.097–0.489, p = 0.0002). The evaluation of Ki-67 expression and the intensity of nuclear staining for survivin and p53 may provide additional information that will allow more accurate stratification of the risk of NMIBC recurrence after TURBT.
C1 [Stec, Rafal] Medical University of Warsaw, Oncology Department, 19/25 Stepinska St., 00-739 Warsaw, Poland.
[Cierniak, Szczepan] Military Institute of Medicine, Pathomorphology Department, 128 Szaserow St., 04-141 Warsaw, Poland.
[Lubas, Arkadiusz] Military Institute of Medicine, Internal Diseases, Nephrology and Dialysis Department, 128 Szaserow St., 04-141 Warsaw, Poland.
[Brzoskowska, Urszula] Military Institute of Medicine, Pathomorphology Department, 128 Szaserow St., 04-141 Warsaw, Poland.
[Syrylo, Tomasz] Military Institute of Medicine, General, Functional and Oncological Urology Department, 128 Szaserow St., 04-141 Warsaw, Poland.
[Zielinski, Henryk] Military Institute of Medicine, General, Functional and Oncological Urology Department, 128 Szaserow St., 04-141 Warsaw, Poland.
[Semeniuk-Wojtas, Aleksandra] Military Institute of Medicine, Oncology Department, 128 Szaserow St., 04-141 Warsaw, Poland.
RP Semeniuk-Wojtas, A (reprint author), Military Institute of Medicine, Oncology Department, 04-141 Warsaw, Poland.
EM osemeniuk@wp.pl
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1211
EP 1219
DI 10.1007/s12253-019-00678-1
PG 9
ER
PT J
AU Mignon, S
Willard-Gallo, K
Van den Eynden, G
Salgado, R
Decoster, L
Marien, MK
Vansteenkiste, FJ
Teugels, E
De Greve, J
AF Mignon, Sacha
Willard-Gallo, Karen
Van den Eynden, Gert
Salgado, Roberto
Decoster, Lore
Marien, M Koen
Vansteenkiste, F Johan
Teugels, Erik
De Greve, Jacques
TI The Relationship Between Tumor-Infiltrating Lymphocytes, PD-L1 Expression, Driver Mutations and Clinical Outcome Parameters in Non-Small Cell Lung Cancer Adenocarcinoma in Patients with a Limited to no Smoking History
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; Tumor infiltrating lymphocytes (TIL); Programmed death-ligand 1 (PD-L1); Programmed death-1 (PD-1); Driver mutations
ID Lung adenocarcinoma; Tumor infiltrating lymphocytes (TIL); Programmed death-ligand 1 (PD-L1); Programmed death-1 (PD-1); Driver mutations
AB Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IVADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin and eosin stained slides from 152 tumor samples. PD-1/PD-L1 expression was retrospectively evaluated with PD-1/PD-L1 immunohistochemistry (IHC) double staining on 74 tumor samples with sufficient residual tissue. PD-L1 expression was analysed on stromal cells of the tumor compartment, the tumor cells and TIL and PD-1 on TIL. Median overall survival (OS) was longer in patients with high stromal TIL infiltration compared to patients with low stromal TIL infiltration (68 weeks vs. 35 weeks respectively; p = 0.003). This was observed most prominently in KRAS mutant tumors (95 weeks vs. 12 weeks; p = 0.003). Only PD-L1 expression on tumor stromal cells influenced OS and indicated a worse prognosis (77 weeks vs 25 weeks; p = 0.013). Stromal TIL counts nor PD-1/PD-L1 expression levels were associated with the presence of driver mutations. The results of the current study reinforce the prognostic role of TIL in lung ADC, which is most prominent in KRAS mutant cancers. The results of the PD-1/PD-L1 analysis suggest that stromal cells can effectively suppress the anti-tumor immune response via the PD-L1 pathway.
C1 [Mignon, Sacha] Universitair Ziekenhuis Brussel, Oncologisch Centrum UZ Brussel, Departement of Medical Oncology, Laarbeeklaan 101, 1090 Brussels, Belgium.
[Willard-Gallo, Karen] Institut Jules Bordet, Molecular Immunology Laboratory, Boulevard de Waterloo 121, 1000 Brussels, Belgium.
[Van den Eynden, Gert] Institut Jules Bordet, Molecular Immunology Laboratory, Boulevard de Waterloo 121, 1000 Brussels, Belgium.
[Salgado, Roberto] Institut Jules Bordet, Molecular Immunology Laboratory, Boulevard de Waterloo 121, 1000 Brussels, Belgium.
[Decoster, Lore] Universitair Ziekenhuis Brussel, Oncologisch Centrum UZ Brussel, Departement of Medical Oncology, Laarbeeklaan 101, 1090 Brussels, Belgium.
[Marien, M Koen] Universiteit Antwerpen, Prinsstraat 13, 2000 Antwerp, Belgium.
[Vansteenkiste, F Johan] University Hospital KU Leuven, Department Respiratory Oncology, Herestraat 49, 3000 Leuven, Belgium.
[Teugels, Erik] Universitair Ziekenhuis Brussel, Oncologisch Centrum UZ Brussel, Departement of Medical Oncology, Laarbeeklaan 101, 1090 Brussels, Belgium.
[De Greve, Jacques] Universitair Ziekenhuis Brussel, Oncologisch Centrum UZ Brussel, Departement of Medical Oncology, Laarbeeklaan 101, 1090 Brussels, Belgium.
RP Mignon, S (reprint author), Universitair Ziekenhuis Brussel, Oncologisch Centrum UZ Brussel, Departement of Medical Oncology, 1090 Brussels, Belgium.
EM sacha.mignon@uzbrussel.be
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1221
EP 1228
DI 10.1007/s12253-019-00670-9
PG 8
ER
PT J
AU Oscorbin, PI
Shadrina, SA
Kozlov, VV
Voitsitsky, EV
Filipenko, LM
AF Oscorbin, P Igor
Shadrina, S Alexandra
Kozlov, V Vadim
Voitsitsky, E Vladimir
Filipenko, L Maxim
TI Absence of EGFR C797S Mutation in Tyrosine Kinase Inhibitor-Naive Non–Small Cell Lung Cancer Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; EGFR; C797S; Osimertinib; Droplet digital PCR
ID Non-small cell lung cancer; EGFR; C797S; Osimertinib; Droplet digital PCR
AB EGFR tyrosine-kinase inhibitors (TKIs) are used as targeted therapeutics for the treatment of advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. EGFR C797S is common causes of acquired resistance to third generation TKIs. There is wide-spread opinion that resistance-conferring mutation present even in a small proportion of cancer cells before the start of therapy could potentially predict poor response to a targeted drug. In our study, we tested whether C797S can be found in previously untreated NSCLCs. We analyzed DNA samples extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue sections of 470 lung adenocarcinoma patients, including 235 samples with activating EGFR mutations. Screening was performed using highly sensitive droplet digital PCR assay. No tumor samples with baseline C797S were identified. C797S does not occur in TKI-naive NSCLCs and provide evidence that screening for this mutation before TKIs administration may not be necessary.
C1 [Oscorbin, P Igor] Institute of Chemical Biology and Fundamental Medicine, Laboratory of Pharmacogenomics, 8 Lavrentiev Avenue, 630090 Novosibirsk, Russian Federation.
[Shadrina, S Alexandra] Novosibirsk State University, 2 Pirogova Street, 630090 Novosibirsk, Russian Federation.
[Kozlov, V Vadim] Institute of Cytology and Genetics, 10 Lavrentiev Avenue, 630090 Novosibirsk, Russian Federation.
[Voitsitsky, E Vladimir] Institute of Cytology and Genetics, 10 Lavrentiev Avenue, 630090 Novosibirsk, Russian Federation.
[Filipenko, L Maxim] Institute of Chemical Biology and Fundamental Medicine, Laboratory of Pharmacogenomics, 8 Lavrentiev Avenue, 630090 Novosibirsk, Russian Federation.
RP Oscorbin, PI (reprint author), Institute of Chemical Biology and Fundamental Medicine, Laboratory of Pharmacogenomics, 630090 Novosibirsk, Russian Federation.
EM osc.igor@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1229
EP 1234
DI 10.1007/s12253-019-00683-4
PG 6
ER
PT J
AU Mohammadpour-Gharehbagh, A
Heidari, Z
Eskandari, M
Aryan, A
Salimi, S
AF Mohammadpour-Gharehbagh, Abbas
Heidari, Zahra
Eskandari, Moein
Aryan, Abtin
Salimi, Saeedeh
TI Association between Genetic Polymorphisms in microRNA Machinery Genes and Risk of Papillary Thyroid Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid carcinoma; DICER1; DROSHA; XPO5; Polymorphism
ID Papillary thyroid carcinoma; DICER1; DROSHA; XPO5; Polymorphism
AB Evidence suggests that the microRNAs are involved in tumorigenesis and progression of various types of malignant tumors. Therefore, the aim of current research was to examine association between genetic variants in the miRNA machinery genes and risk of papillary thyroid carcinoma(PTC) in Iranian population. Peripheral blood samples were collected from 120 PTC patients and 130 healthy subjects. Genotyping of polymorphisms in miRNA Machinery genes (DICER1 rs3742330, DROSHA rs6877842 and XPO5 rs11077) polymorphisms was performed using PCR-RFLP method. Chi square and independent sample t tests were applied for categorical and continuous variables, respectively. In this study, we found that frequency of DICER1 rs3742330G allele was significantly higher in controls compared to PTC patients. In addition, the DICER1 rs3742330 polymorphism was associated with lower risk of PTC in dominant (AG + GG vs. AA, OR = 0.5, 95%CI = 0.3–0.9, P = 0.03) model. No association was found between DROSHA rs6877842 and XPO5 rs11077 polymorphisms and PTC neither in dominant nor in recessive and allelic models. The frequency of DROSHA rs6877842GC genotype was higher in PTC patients with smaller tumor size (<1). Therefore, this polymorphism could be a protective factor for tumor development in PTC patients (OR = 0.3, 95%CI = 0.1–1, P = 0. 04). The current study indicated that DICER1 rs3742330 polymorphism was associated with lower risk of PTC. Furthermore, DROSHA rs6877842 polymorphism could be a protective factor for tumor development in PTC patients.
C1 [Mohammadpour-Gharehbagh, Abbas] Zahedan University of Medical Sciences, School of Medicine, Department of Clinical BiochemistryZahedan, Iran.
[Heidari, Zahra] Zahedan University of Medical Sciences, Department of EndocrinologyZahedan, Iran.
[Eskandari, Moein] Zahedan University of Medical Sciences, School of Paramedical Sciences, Department of Laboratory SciencesZahedan, Iran.
[Aryan, Abtin] Zahedan University of Medical Sciences, Radiology departmentZahedan, Iran.
[Salimi, Saeedeh] Zahedan University of Medical Sciences, School of Medicine, Department of Clinical BiochemistryZahedan, Iran.
RP Salimi, S (reprint author), Zahedan University of Medical Sciences, School of Medicine, Department of Clinical Biochemistry, Zahedan, Iran.
EM sasalimi@yahoo.com;salimis@zaums.ac.ir
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Erler P, Keutgen XM, Crowley MJ, Zetoune T, Kundel A, Kleiman D, Beninato T, Scognamiglio T, Elemento O, Zarnegar R, 2014, Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer. Surgery 156(6):1342–1350
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Yuan L, Chu H,Wang M,Gu X, ShiD, Ma L, Zhong D, Du M, Li P, Tong N, Fu G, Qin C, Yin C, Zhang Z, 2013, Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk. PLoS One 8(11):e81524. , DOI 10. 1371/journal.pone.0081524
Sung H, Jeon S, Lee KM, Han S, Song M, Choi JY, Park SK, Yoo KY, Noh DY, Ahn SH, Kang D, 2012, Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival. BMC Cancer 12:195. , DOI 10.1186/1471-2407- 12-195
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1235
EP 1241
DI 10.1007/s12253-019-00688-z
PG 7
ER
PT J
AU Krafft, U
Tschirdewahn, S
Hess, J
Harke, N
Hadaschik, AB
Nyirady, P
Szendroi, A
Szucs, M
Modos, O
Olah, Cs
Szekely, E
Reis, H
Szarvas, T
AF Krafft, Ulrich
Tschirdewahn, Stephan
Hess, Jochen
Harke, N. Nina
Hadaschik, A Boris
Nyirady, Peter
Szendroi, Attila
Szucs, Maria
Modos, Orsolya
Olah, Csilla
Szekely, Eszter
Reis, Henning
Szarvas, Tibor
TI STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; STIP1; Cisplatin; Resistance
ID Bladder cancer; STIP1; Cisplatin; Resistance
AB To optimize treatment decisions in advanced bladder cancer (BC), we aimed to assess the therapy predictive value of STIP1 with regard to cisplatin therapy. Cisplatin-based chemotherapy represents the standard first-line systemic treatment of advanced bladder cancer. Since novel immuno-oncologic agents are already available for cisplatin-resistant or ineligible patients, biological markers are needed for the prediction of cisplatin resistance. STIP1 expression was analyzed in paraffin-embedded bladder cancer tissue samples of 98 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Furthermore, prechemotherapy serum STIP1 concentrations were determined in 48 BC patients by ELISA. Results were correlated with the clinicopathological and follow-up data. Stronger STIP1 nuclear staining was associated with worse OS in both the whole patient group (p = 0.034) and the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.043). These correlations remained significant also in the multivariable analyses (p =0.035 and p = 0.040). Stronger STIP1 cytoplasmatic immunostaining correlated with shorter PFS both in the whole cohort (p = 0.045) and in the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.026). Elevated STIP1 serum levels were associated with older patient’s age, but we found no correlation between STIP1 serum levels and patients’ outcome. Our results suggest that tissue STIP1 analysis might be used for the prediction of cisplatin-resistance in BC. In contrast, pretreatment STIP1 serum levels showed no predictive value for chemotherapy response and survival.
C1 [Krafft, Ulrich] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Tschirdewahn, Stephan] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Hess, Jochen] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Harke, N. Nina] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Hadaschik, A Boris] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
[Nyirady, Peter] Semmelweis University, Department of UrologyBudapest, Hungary.
[Szendroi, Attila] Semmelweis University, Department of UrologyBudapest, Hungary.
[Szucs, Maria] Semmelweis University, Department of UrologyBudapest, Hungary.
[Modos, Orsolya] Semmelweis University, Department of UrologyBudapest, Hungary.
[Olah, Csilla] Semmelweis University, Department of UrologyBudapest, Hungary.
[Szekely, Eszter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Reis, Henning] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Szarvas, Tibor] University of Duisburg-Essen, Department of Urology, Hufelandstr. 55, 45147 Essen, Germany.
RP Szarvas, T (reprint author), University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
EM sztibusz@gmail.com
CR Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H et al, 2013, Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur JCancer 49:1374–1403
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Hemdan T, Malmstrom P-UU, Jahnson S, Segersten U, 2015, Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder Cancer: a validation study. J Urol 194:1575–1581
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Krafft U, Tschirdewahn S,Hess J,HarkeNN, Hadaschik B,Olah C, Krege S, Nyirady P, Szendroi A, Szucs M, Modos O, Szekely E, Reis H, Szarvas T, 2019, Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer. Urol Oncol. , DOI 10.1016/j.urolonc.2019.04.015
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1243
EP 1249
DI 10.1007/s12253-019-00689-y
PG 7
ER
PT J
AU Rakhshan, A
Esmaeili, HM
Kahaei, SM
Taheri, M
Omrani, DM
Noroozi, R
Ghafouri-Fard, S
AF Rakhshan, Azadeh
Esmaeili, Hossein Mohammad
Kahaei, Salar Mir
Taheri, Mohammad
Omrani, Davood Mir
Noroozi, Rezvan
Ghafouri-Fard, Soudeh
TI A Single Nucleotide Polymorphism in GAS5 lncRNA is Associated with Risk of Bladder Cancer in Iranian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Bladder cancer; GAS5; lncRNA
ID Bladder cancer; GAS5; lncRNA
AB Down-regulation of the long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) has a pathogenic role in bladder cancer. Moreover, genomic variants of this lncRNA have been associated with risk of diverse cancers. In the present project, we genotyped two putative functional SNPs (rs2067079 and rs6790) in 122 bladder cancer patients and 150 age- and sex matched healthy subjects. The rs2067079 was associated risk of bladder cancer in recessive inheritance model (TT vs.CC + CT: OR (95% Confidence interval (CI)) = 2.67 (1.27–5.62), adjusted P value = 0.02). The T G haplotype (rs2067079 and rs6790) increased the risk of bladder cancer in the assessed population (OR (95% CI) = 1.73 (1.18–2.56), adjusted P value = 0.02). Consequently, in the current project we introduced a novel risk locus for bladder cancer in Iranian population.
C1 [Rakhshan, Azadeh] Shahid Beheshti University of Medical Sciences, Urogenital Stem Cell Research CenterTehran, Iran.
[Esmaeili, Hossein Mohammad] High Institute for Research and Education in Transfusion Medicine, Blood Transfusion Research CenterTehran, Iran.
[Kahaei, Salar Mir] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Taheri, Mohammad] Shahid Beheshti University of Medical Sciences, Department of Medical GeneticsTehran, Iran.
[Omrani, Davood Mir] Shahid Beheshti University of Medical Sciences, Urology and Nephrology Research CenterTehran, Iran.
[Noroozi, Rezvan] Shahid Beheshti University of Medical Sciences, Phytochemistry Research CenterTehran, Iran.
[Ghafouri-Fard, Soudeh] High Institute for Research and Education in Transfusion Medicine, Blood Transfusion Research CenterTehran, Iran.
RP Taheri, M (reprint author), Shahid Beheshti University of Medical Sciences, Department of Medical Genetics, Tehran, Iran.
EM mohammad_823@yahoo.com
CR Rafiemanesh H, Lotfi Z, Bakhtazad S, Ghoncheh M, Salehiniya H, 2018, The epidemiological and histological trend of bladder cancer in Iran. J Cancer Res Ther 14(3):532–536
Gu J, Wu XF, 2011, Genetic susceptibility to bladder cancer risk and outcome. Pers Med 8(3):365–374
Taheri M, Omrani MD, Ghafouri-Fard S, 2018, Long non-coding RNA expression in bladder cancer. Biophys Rev 10(4):1205–1213
Minotti L, Agnoletto C, Baldassari F, Corra F, Volinia S, 2018, SNPs and somatic mutation on long non-coding RNA: new frontier in the cancer studies? High-throughput. 7(4)
Zhang H, Guo Y, Song Y, Shang C, 2017, Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma. Cancer Chemother Pharmacol 79(1):49–55
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Wang M, Guo C, Wang L, Luo G, Huang C, Li YW et al, 2018, Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription. Cell Death Dis 9
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1251
EP 1254
DI 10.1007/s12253-019-00693-2
PG 4
ER
PT J
AU Jin, G
Fan, XM
Li, KX
Niu, ShH
Zhang, QY
AF Jin, Ge
Fan, Xiao-Mei
Li, Kui-Xiu
Niu, Shu-Huai
Zhang, Qian-Ying
TI The Association between Epidermal Growth Factor Receptor Single Nucleotide Polymorphisms and Radiochemotherapy Response in Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Epidermal growth factor receptor; Single nucleotide polymorphism; Radio-chemotherapy
ID Cervical cancer; Epidermal growth factor receptor; Single nucleotide polymorphism; Radio-chemotherapy
AB Emerging data reveal that epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) can act as efficacy indicators for tumor treatment. Here, the association between EGFR R497K (rs11543848) and -216G/T (rs712829) SNPs and radio-chemotherapy response in cervical cancer was investigated. EGFR R497K and -216G/T genotypes were analyzed by polymerase chain reaction-ligation detection reaction in 196 cervical cancer patients receiving radiotherapy alone, or in combination with chemotherapy. Compared with the 497G/G genotype, the A/A genotype significantly increased sensitivity to radio-chemotherapy treatment (adjusted OR = 0.244, 95% CI = 0.087–0.680). Sensitivity to radio-chemotherapy was not significantly different in carriers of the ‘T’ allele than that measured for the -216G/G genotype (adjusted OR = 2.412, 95%CI = 0.856– 6.979). Additionally, the 497A/A genotype conferred a reduced risk of recurrence or metastasis than did the G/G genotype (adjusted OR = 0.248, 95% CI = 0.078–0.786, P< 0.05). Moreover, carriers of the ‘T’ allele did not have significantly modified risk of recurrence or metastasis compared with those with the -216G/G genotype (adjusted OR = 1.027, 95% CI = 0.324–3.253). Multivariate analysis revealed an association between clinical stage and treatment response (adjusted OR = 3.575, 95% CI = 1.662–7.692) and between age and the risk of recurrence or metastasis (adjusted OR = 0.319, 95%CI = 0.148–0.691). Our results show that, in patients with cervical cancer, the R497K polymorphism is correlated with treatment response and the risk of recurrence or metastasis. The R497K SNP might be a genetic marker for prediction of radio-chemotherapy response and the risk of recurrence and/or metastasis in patients with cervical cancer.
C1 [Jin, Ge] the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, #12, Jiankang Road, 050011 Shijiazhuang, Hebei province, China.
[Fan, Xiao-Mei] the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, #12, Jiankang Road, 050011 Shijiazhuang, Hebei province, China.
[Li, Kui-Xiu] the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, #12, Jiankang Road, 050011 Shijiazhuang, Hebei province, China.
[Niu, Shu-Huai] the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, #12, Jiankang Road, 050011 Shijiazhuang, Hebei province, China.
[Zhang, Qian-Ying] the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, #12, Jiankang Road, 050011 Shijiazhuang, Hebei province, China.
RP Fan, XM (reprint author), the Fourth Hospital of Hebei Medical University, Department of Gynecologic Oncology, 050011 Shijiazhuang, China.
EM fanxiaomei2006@sina.com
CR Lee KB, Shim SH, Lee JM, 2018, Comparison between adjuvant chemotherapy and adjuvant radiotherapy/chemoradiotherapy after radical surgery in patients with cervical cancer: a meta-analysis. J Gynecol Oncol 29
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Binder ZA, Thorne AH, Bakas S,Wileyto EP, Bilello M, Akbari H, Rathore S, Ha SM, Zhang L, Ferguson CJ, Dahiya S, Bi WL, Reardon DA, Idbaih A, Felsberg J, Hentschel B, Weller M, Bagley SJ, Morrissette JJD, Nasrallah MP, Ma J, Zanca C, Scott AM, Orellana L, Davatzikos C, Furnari FB, O'Rourke DM, 2018, Epidermal growth factor receptor extracellular domain mutations in glioblastoma present opportunities for clinical imaging and therapeutic development. Cancer Cell 34:163–177 e167
Arena S, Bellosillo B, Siravegna G,Martinez A, Canadas I, Lazzari L, Ferruz N, Russo M, Misale S, Gonzalez I, IglesiasM, Gavilan E, Corti G, Hobor S, Crisafulli G, Salido M, Sanchez J, Dalmases A, Bellmunt J,De Fabritiis G, Rovira A, Di Nicolantonio F, Albanell J, Bardelli A, Montagut C, 2015, Emergence of multiple EGFR extracellular mutations during Cetuximab treatment in colorectal Cancer. Clin Cancer Res 21:2157–2166
Goncalves A, Esteyries S, Taylor-Smedra B, Lagarde A, Ayadi M, Monges G, Bertucci F, Esterni B, Delpero JR, Turrini O, Lelong B, Viens P, Borg JP, Birnbaum D, Olschwang S, Viret F, 2008, A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment. BMC Cancer 8:169
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1255
EP 1261
DI 10.1007/s12253-019-00690-5
PG 7
ER
PT J
AU Okamoto, A
Sakakura, K
Takahashi, H
Motegi, Si
Kaira, K
Yokobori-Kuwabara, Y
Ishikawa, O
Chikamatsu, K
AF Okamoto, Ayako
Sakakura, Koichi
Takahashi, Hideyuki
Motegi, Sei-ichiro
Kaira, Kyoichi
Yokobori-Kuwabara, Yuki
Ishikawa, Osamu
Chikamatsu, Kazuaki
TI Immunological and Clinicopathological Significance of MFG-E8 Expression in Patients with Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Milk fat globule-epidermal growth factor 8 (MFG-E8); Oral squamous cell carcinoma (OSCC); Tumor microenvironment (TME); Immune suppression
ID Milk fat globule-epidermal growth factor 8 (MFG-E8); Oral squamous cell carcinoma (OSCC); Tumor microenvironment (TME); Immune suppression
AB Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by the activated macrophages and acts as a bridge between apoptotic cells and phagocytes. Aside from macrophages, a variety of malignant cells also express MFG-E8. The objective of this study is to elucidate the clinical relevance and significance of MFG-E8 in the tumor microenvironment (TME) of patients with oral squamous cell carcinoma (OSCC). We investigated MFG-E8 expression in 74 patients with OSCC by immunohistochemistry and evaluated the relationship between MFG-E8 expression and various clinicopathological factors including immune cell infiltration. MFG-E8 expression was detected in 34 of 74 (45.9%) patients with OSCC and a significant correlation was observed with levels of infiltrating T cells, macrophages, and immunosuppressive M2 macrophages. Furthermore, MFG-E8 expression was also associated with clinical stage, lymphatic/vascular invasion, and Ki-67+ tumor cells but not with survival. Our results suggest that MFG-E8 may play an important role in shaping the immune suppressive network in TME as well as tumor progression.
C1 [Okamoto, Ayako] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
[Sakakura, Koichi] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
[Takahashi, Hideyuki] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
[Motegi, Sei-ichiro] Gunma University, Graduate School of Medicine, Department of DermatologyMaebashi, Japan.
[Kaira, Kyoichi] Gunma University, Graduate School of Medicine, Department of Oncology Clinical DevelopmentMaebashi, Japan.
[Yokobori-Kuwabara, Yuki] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
[Ishikawa, Osamu] Gunma University, Graduate School of Medicine, Department of DermatologyMaebashi, Japan.
[Chikamatsu, Kazuaki] Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
RP Chikamatsu, K (reprint author), Gunma University, Graduate School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 3718511 Gunma, Japan.
EM tikamatu@gunma-u.ac.jp
CR Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC, Vonderheide RH, Pittet MJ, Jain RK, Zou W, Howcroft TK, Woodhouse EC, Weinberg RA, Krummel MF, 2018, Understanding the tumor immune microenvironment, TIME, for effective therapy. Nat Med 24:541–550
Quail DF, Joyce JA, 2013, Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437
Balkwill FR, Capasso M, Hagemann T, 2012, The tumor microenvironment at a glance. J Cell Sci 125:5591–5596
Gajewski TF, Schreiber H, Fu Y-X, 2013, Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 14: 1014–1022
Munn DH, Bronte V, 2016, Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol 39:1–6
Chen DS, Mellman I, 2013, Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10
Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S, 2002, Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187
Asano K, Miwa M, Miwa K, Hanayama R, Nagase H, Nagata S, Tanaka M, 2004)Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice. J Exp Med 200:459–467
Jinushi M, Nakazaki Y, Dougan M, Carrasco DR, Mihm M, Dranoff G, 2007, MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF. J Clin Invest 117:1902–1913
Oba J, Moroi Y, Nakahara T, Abe T, Hagihara A, Furue M, 2011, Expression of milk fat globle epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma. Br J Dermatol 165:506–512
Yamazaki M, Maruyama S, Abe T, Essa A, Babkair H, Cheng J et al, 2014, MFG-E8 expression for progression of oral squamous cell carcinoma and for self-clearance of apoptotic cells. Lab Investig 94: 1260–1272
Jia M, Yao H, Chen C, Wang Y, Wang H, Cui T, Zhu J, 2017, Prognostic correlation between MFG-E8 expression level and colorectal cancer. Arch Med Res 48:270–275
Yamada K, Uchiyama A, Uehara A, Perera B, Ogino S, Yokoyama Y, Takeuchi Y, Udey MC, Ishikawa O, Motegi SI, 2016, MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cellinduced angiogenesis and M2 polarization of tumor-associated macrophages. Cancer Res 76:4283–4292
Silvestre JS, Thery C, Hamard G, Boddaert J, Aguilar B, Delcayre A et al, 2005, Lactadherin promotes VEGF-dependent neovascularization. Nat Med 11:499–506
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Soki FN, Koh AJ, Jones JD, Kim YW, Dai J, Keller ET, Pienta KJ, Atabai K, Roca H, McCauley LK, 2014, Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8, MFG-E8)-mediated efferocytosis. J Biol Chem 289: 24560–24572
Uchiyama A, Yamada K, Ogino S, Yokoyama Y, Takeuchi Y, Udey MC, Ishikawa O, Motegi SI, 2014, MFG-E8 regulates angiogenesis in cutaneous wound healing. Am J Pathol 184:1981–1990
Dai W, Li Y, Lv YN, Wei CD, Zheng HY, 2014, The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8, in patients with coronary atherosclerotic heart disease. Atherosclerosis 233:661–665
Motegi S, LeitnerWW, Lu M, Tada Y, Sardy M,Wu C et al, 2011, Pericyte-derived MFG-E8 regulates pathologic angiogenesis. Arterioscler Thromb Vasc Biol 31:2024–2034
Fonseca C, Dranoff G, 2008, Capitalizing on the immunogenicity of dying tumor cells. Clin Cancer Res 14:1603–1608
Quail DF, Joyce JA, 2013)Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437
Noy R, Pollard JW, 2014, Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:49–61
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1263
EP 1268
DI 10.1007/s12253-019-00692-3
PG 6
ER
PT J
AU Zhou, Sh
Tu, J
Ding, Sh
Lu, G
Lin, Z
Ding, Y
Deng, B
Zhang, Y
Xiao, W
Gong, W
AF Zhou, Shuaiyang
Tu, Jin
Ding, Shizhen
Lu, Guotao
Lin, Zhijie
Ding, Yanbing
Deng, Bing
Zhang, Yu
Xiao, Weiming
Gong, Weijuan
TI High Expression of Angiopoietin-like Protein 4 in Advanced Colorectal Cancer and its Association with Regulatory T Cells and M2 Macrophages
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Angiopoietin-like protein 4; Treg; M2 macrophage; Colorectal cancer; Correlation
ID Angiopoietin-like protein 4; Treg; M2 macrophage; Colorectal cancer; Correlation
AB Colorectal cancer (CRC) is one of the most aggressive tumours in the human digestive system. Most CRC patients have poor prognosis due to metastasis and recurrence. Angiopoietin-like 4 (ANGPTL4) is involved in tumour development. Regulatory T (Treg) cells and M2 macrophages promote tumour growth and metastasis. Herein, we explored the changes of ANGPTL4 expression in CRC patients at different stages and observed whether in situ tumour-Treg and -M2 macrophages are correlated with ANGPTL4 expression. Serum ANGPTL4 (sANGPTL4) levels of 70 CRC patients and 10 healthy controls were detected by ELISA. ANGPTL4, Foxp3 and CD163 expression levels in CRC tissues were measured by immunohistochemistry. Recombinant ANGPTL4 (rANGPTL4) proteins were further added into cell-culture systems for induction of Treg cells and M2 macrophages. The results showed both sANGPTL4 and in situ tumour-ANGPTL4 expression levels increased in Dukes C–D stage CRC patients. Foxp3+ and CD163+ cells in tumour tissue sections were also more intensive in Dukes C–D stage patients than in Dukes A–B stage patients. Foxp3+ and CD163+ cells in tumour tissues were positively correlated with both tissue and sANGPTL4 expression (P < 0.01). Recombinant ANGPTL4 promoted the induction of murine Treg cells and M2 macrophages ex vivo. Therefore, elevated ANGPTL4 expression could be a marker for advanced CRC. Treg cell and M2 macrophage induction could be one of the mechanisms of tumour promotion mediated by ANGPTL4.
C1 [Zhou, Shuaiyang] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Tu, Jin] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Ding, Shizhen] Yangzhou University, School of Medicine, Department of Basic Medicine, 225001 Yangzhou, China.
[Lu, Guotao] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Lin, Zhijie] Yangzhou University, School of Medicine, Department of Basic Medicine, 225001 Yangzhou, China.
[Ding, Yanbing] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Deng, Bing] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Zhang, Yu] Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, 225001 Yangzhou, China.
[Xiao, Weiming] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
[Gong, Weijuan] Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
RP Gong, W (reprint author), Yangzhou University, Affiliated Hospital, Department of Gastroenterology, 225001 Yangzhou, China.
EM wjgong@yzu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1269
EP 1278
DI 10.1007/s12253-019-00695-0
PG 10
ER
PT J
AU Gao, Bsh
Rong, Chsh
Xu, Hm
Sun, T
Hou, J
Xu, Y
AF Gao, Bao-shan
Rong, Chun-shu
Xu, Hong-mei
Sun, Tao
Hou, Jie
Xu, Ying
TI Peptidyl Arginine Deiminase, Type II (PADI2) Is Involved in Urothelial Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PADI2; Urothelial bladder cancer; Overexpressed; Tissue microarray analysis
ID PADI2; Urothelial bladder cancer; Overexpressed; Tissue microarray analysis
AB Peptidyl arginine deiminase, type II (PADI2) expression has been shown to potentiate multiple different carcinogenesis pathway including breast carcinoma and spontaneous skin neoplasia. The objective of this study was to examine the role of PADI2 in urothelial bladder cancer which has not been evaluated previously. Analysis of mutation and genome amplification of bladder cancer within The Cancer Genome Atlas (TCGA) showed that PADI2 is both mutated and amplified in a cohort of bladder cancer patients, with the largest number of mutations detected in urothelial bladder cancer. Even though PADI2 expression was not significantly correlated to survival in bladder cancer patients, it was significantly overexpressed at the mRNA and protein levels, as revealed by TCGA data and immunohistochemistry analysis, respectively. PADI2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. RNAi mediated silencing of PADI2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of PADI2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, PADI2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of PADI2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where PADI2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. PADI2 silencing did not affect proliferation rates and hence this would suggest that PADI2 knockdown is perhaps causing increased apoptosis as well as transition through the cell cycle, which needs to be confirmed in future studies. Our results reveal a yet undefined role of PADI2 as an oncogene in urothelial bladder cancer.
C1 [Gao, Bao-shan] The First Hospital of Jilin University, Urology Center, No.71, Xinmin Street, 130021 Changchun, Jilin, China.
[Rong, Chun-shu] The Affiliated Hospital to Changchun University of Chinese Medicine, Department of Encephalopathy Diseases, 130021 Changchun, Jilin, China.
[Xu, Hong-mei] The First Hospital of Jilin University, Obstetric Department, 130021 Changchun, Jilin, China.
[Sun, Tao] The First Hospital of Jilin University, Urology Center, No.71, Xinmin Street, 130021 Changchun, Jilin, China.
[Hou, Jie] The First Hospital of Jilin University, Urology Center, No.71, Xinmin Street, 130021 Changchun, Jilin, China.
[Xu, Ying] The First Hospital of Jilin University, Urology Center, No.71, Xinmin Street, 130021 Changchun, Jilin, China.
RP Xu, Y (reprint author), The First Hospital of Jilin University, Urology Center, 130021 Changchun, China.
EM yingxu_jilinuni@126.com
CR Murta-Nascimento C, Schmitz-Drager BJ, ZeegersMP, Steineck G, Kogevinas M, Real FX, Malats N, 2007, Epidemiology of urinary bladder cancer: from tumor development to patient's death.World J Urol 25(3):285–295
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Zeegers MPA, Tan FES, Dorant E, Van dB, Piet A, 2015, The impact of characteristics of cigarette smoking on urinary tract cancer risk. Cancer 89(3):630–639
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1279
EP 1285
DI 10.1007/s12253-019-00687-0
PG 7
ER
PT J
AU Kadletz, CL
Brkic, FF
Jank, JB
Schneider, S
Cede, J
Seemann, R
Gruber, SE
Gurnhofer, E
Heiduschka, G
Kenner, L
AF Kadletz, C Lorenz
Brkic, F Faris
Jank, J Bernhard
Schneider, Sven
Cede, Julia
Seemann, Rudolf
Gruber, S Elisabeth
Gurnhofer, Elisabeth
Heiduschka, Gregor
Kenner, Lukas
TI AF1q Expression Associates with CD44 and STAT3 and Impairs Overall Survival in Adenoid Cystic Carcinoma of the Head and Neck
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Adenoid cystic carcinoma; AF1q; Wnt; STAT3; Prognosis
ID Adenoid cystic carcinoma; AF1q; Wnt; STAT3; Prognosis
AB Salivary gland malignancies of the head and neck form a heterogeneous group. Adenoid cystic carcinomas are an aggressive entity of salivary gland malignancies characterized by frequent distant metastases and poor response to radio- and chemotherapy. AF1Q is a MLL fusion partner, which can activate Wnt and STAT3 signaling. Recently, overexpression of AF1q has been identified as a poor prognosticator in patients of different malignancies. A total of 46 patients with adenoid cystic carcinoma were immunohistochemically evaluated for expression of AF1q and clinical outcome was analyzed in this context. Additionally, STAT3 and the Wnt downstream target CD44 were investigated and correlated with AF1q. AF1q was overexpressed in 52.2%. Overexpression of AF1q was associated with poorer overall survival (p = 0.03). Additionally, lymph node metastases and solid tumor parts were more frequently observed in AF1qhigh patients (p = 0.07 and 0.05, respectively). AF1q did not influence the occurrence of distant metastases. Expression of AF1q was associated with higher levels of STAT3 and CD44 (p = 0.003 and 0.006, respectively). AF1q is a novel prognostic marker for poor overall survival in adenoid cystic carcinoma patients. The deleterious effects on survival may be a result of promotion of the STAT3 and Wnt pathway.
C1 [Kadletz, C Lorenz] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck SurgeryVienna, Austria.
[Brkic, F Faris] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck SurgeryVienna, Austria.
[Jank, J Bernhard] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck SurgeryVienna, Austria.
[Schneider, Sven] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck SurgeryVienna, Austria.
[Cede, Julia] Medical University of Vienna, Department of Cranio-maxillo and Facial SurgeryVienna, Austria.
[Seemann, Rudolf] Medical University of Vienna, Department of Cranio-maxillo and Facial SurgeryVienna, Austria.
[Gruber, S Elisabeth] Medical University of Vienna, Department of SurgeryVienna, Austria.
[Gurnhofer, Elisabeth] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal PathologyVienna, Austria.
[Heiduschka, Gregor] Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck SurgeryVienna, Austria.
[Kenner, Lukas] Medical University of Vienna, Department of Experimental Pathology and Laboratory Animal PathologyVienna, Austria.
RP Kadletz, CL (reprint author), Medical University of Vienna, Department of Oto-rhino-laryngology and Head and Neck Surgery, Vienna, Austria.
EM lorenz.kadletz@meduniwien.ac.at
CR Sood S, McGurk M, Vaz F, 2016, J Larnygol Otol 130:S142
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1287
EP 1292
DI 10.1007/s12253-019-00696-z
PG 6
ER
PT J
AU Liu, Q
Pan, Lz
Hu, M
Ma, Jy
AF Liu, Qin
Pan, Liang-zhi
Hu, Min
Ma, Jian-ying
TI Molecular Network-Based Identification of Circular RNA-Associated ceRNA Network in Papillary Thyroid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Papillary thyroid cancer; circRNA; Competitive endogenous RNA; microRNA
ID Papillary thyroid cancer; circRNA; Competitive endogenous RNA; microRNA
AB Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. Nevertheless, their function and underlying mechanisms in papillary thyroid cancer (PTC) remains largely unknown. This study aimed to describe the regulatory mechanisms in PTC. The expression profile of circRNA was download from the Gene ExpressionOmnibus (GEO) database. The mRNA and miRNA data of PTC was downloaded from The Cancer Genome Atlas (TCGA) database. The circRNA-miRNA-mRNA network by Cytoscape. The interactions between proteins were analyzed using the STRING database and hubgenes were identified using MCODE plugin. Then, we conducted a circRNA-miRNA-hubgenes regulatory module. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were conducted using R packages “Clusterprofile”. We identified 14 differential expression circRNAs (DEcircRNA), 3106 differential expression mRNAs (DEmRNA), 142 differential expression miRNAs (DEmiRNA) and in PTC. Twelve circRNAs, 33 miRNAs, and 356 mRNAs were identified to construct the ceRNA network of PTC. PPI network and module analysis identified 5 hubgenes. Then, a circRNA-miRNA-hubgene subnetwork was constructed based on the 2 DEcircRNAs, 3 DEmiRNAs, and 4 DEmRNAs. GO and KEGG pathway analysis indicated DEmRNAs might be associated with PTC onset and progression. These ceRNAs are critical in the pathogenesis of PTC and may serve as future therapeutic biomarkers.
C1 [Liu, Qin] Hubei Polytechnic University, Huangshi Central Hospital of Edong Healthcare Group, Department of Breast Surgery, Thyroid Surgery, No.141, Tianjin RoadHuangshi, Hubei, China.
[Pan, Liang-zhi] Hubei Polytechnic University, Huangshi Central Hospital (Pu Ai Hospital) of Edong Healthcare Group, Personnel SectionHuangshi, Hubei, China.
[Hu, Min] Hubei Polytechnic University, Huangshi Central Hospital (Pu Ai Hospital) of Edong Healthcare Group, Personnel SectionHuangshi, Hubei, China.
[Ma, Jian-ying] Hubei Polytechnic University, Huangshi Central Hospital of Edong Healthcare Group, Department of Breast Surgery, Thyroid Surgery, No.141, Tianjin RoadHuangshi, Hubei, China.
RP Ma, Jy (reprint author), Hubei Polytechnic University, Huangshi Central Hospital of Edong Healthcare Group, Department of Breast Surgery, Thyroid Surgery, Huangshi, China.
EM majianying2015@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1293
EP 1299
DI 10.1007/s12253-019-00697-y
PG 7
ER
PT J
AU Liu, Ch
Xu, D
Xue, B
Liu, B
Li, J
Huang, J
AF Liu, Chao
Xu, Dingwei
Xue, Bai
Liu, Bolin
Li, Jing
Huang, Jie
TI Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; RUNX1; VEGFA; Tumor suppression
ID Hepatocellular carcinoma; RUNX1; VEGFA; Tumor suppression
AB Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and occurs in people with chronic liver diseases. Current treatment methods include surgery, transplant, and chemotherapy. Our study demonstrates runt-related transcription factor 1 (RUNX1) as a novel molecule in the initiation and development of HCC, and the role of its interaction with vascular endothelial growth factor A (VEGFA) in HCC. We showed the suppressive role of RUNX1 in the proliferation and migration of hepatocytes. In addition, the repressor RUNX1 functioned as a transcription factor on the promoter of VEGFA to inhibit the expression of VEGFA. Study in the HCC cells demonstrated that the suppression of HCC proliferation and migration was masked in the presence of overexpressed VEGFA. Introduction of RUNX1 into HCC mice model significantly limited the tumor growth. In summary, our study demonstrated that RUNX1 functions as a repressor in the HCC and this suppressive function was dependent on its effect on VEGFA.
C1 [Liu, Chao] Jiangsu College of Nursing, School of Medical Technology, 223005 Huainan, Jiangsu Province, China.
[Xu, Dingwei] The Second Affiliation Hospital of Kunming Medical University, Department of Hepatobiliary Surgery, 243 Dianmian Avenue, Wuhua District, 650101 Kunming, Yunnan Province, China.
[Xue, Bai] Jiangsu College of Nursing, School of Medical Technology, 223005 Huainan, Jiangsu Province, China.
[Liu, Bolin] Jiangsu College of Nursing, School of Medical Technology, 223005 Huainan, Jiangsu Province, China.
[Li, Jing] Jiangsu College of Nursing, School of Medical Technology, 223005 Huainan, Jiangsu Province, China.
[Huang, Jie] The Second Affiliation Hospital of Kunming Medical University, Department of Hepatobiliary Surgery, 243 Dianmian Avenue, Wuhua District, 650101 Kunming, Yunnan Province, China.
RP Huang, J (reprint author), The Second Affiliation Hospital of Kunming Medical University, Department of Hepatobiliary Surgery, 650101 Kunming, China.
CR Tunissiolli NM, Castanhole-Nunes MMU, Biselli-Chicote PM, Pavarino EC, da Silva RF, da Silva RC, Goloni-Bertollo EM, 2017, Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy. Asian Pac J Cancer Prev 18(4):863– 872. , DOI 10.22034/APJCP.2017.18.4.863
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1301
EP 1311
DI 10.1007/s12253-019-00694-1
PG 11
ER
PT J
AU Foda, AMA
Rafi, S
Ikram, N
Alam, SM
Ayesha, S
AF Foda, AlRahman Mohammad Abd
Rafi, Samia
Ikram, Nadeem
Alam, Syed Mariya
Ayesha, Sana
TI Spinal Versus Intracranial Meningioma: Aberrant Expression of CD10 and Inhibin with Relation to Clinicopathological Features and Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD10; Inhibin; Spinal; Intracranial; Meningioma
ID CD10; Inhibin; Spinal; Intracranial; Meningioma
AB CD10 and inhibin are used mainly in CNS pathology to distinguish hemangioblastoma from metastatic clear cell renal cell carcinoma. Some meningiomas can mimic both tumors and so we aimed at this study to investigate the expression of both markers in a large number of meningioma cases. One hundred thirty-four meningioma samples were collected, 14 of them were spinal and 120 were intracranial. Manual TMA blocks were constructed using modified mechanical pencil tip method and immunohistochemistry for CD10 and inhibin was done. Intracranial meningioma occurred in significantly younger age than spinal ones. Most of spinal meningiomas were of transitional histology. CD10 was expressed in 14% of cases with significant positivity in spinal rather than intracranial cases. Transitional meningiomas showed the highest positivity for CD10 expression, while the least positive was the meningiotheliomatous type. Inhibin was expressed in 6% of cases with no significant relation to clinicopathological and histological features. There was no significant relationship between the expression of CD10 and inhibin expression in meningiomas. In conclusion, spinal meningiomas differ than intracranial ones in many clinicopathological and biological aspects. Among these differences is CD10 expression being more expressed in spinal meningiomas. However CD10 and inhibin are aberrantly expressed in a proportion of meningiomas, both have no relations to poor prognostic factors but more caution should be exerted during usage of these markers in diagnosis of hemangioblastoma and metastatic RCC. Further studies are suggested for exploring more biological differences between spinal and intracranial meningiomas.
C1 [Foda, AlRahman Mohammad Abd] Mansoura University, Faculty of Medicine, Department of PathologyMansoura, Egypt.
[Rafi, Samia] Batterjee Medical College for Sciences and TechnologyJeddah, Saudi Arabia.
[Ikram, Nadeem] Batterjee Medical College for Sciences and TechnologyJeddah, Saudi Arabia.
[Alam, Syed Mariya] Batterjee Medical College for Sciences and TechnologyJeddah, Saudi Arabia.
[Ayesha, Sana] Tribhuvan University, Faculty of MedicineKirtipur, Nepal.
RP Foda, AMA (reprint author), Mansoura University, Faculty of Medicine, Department of Pathology, Mansoura, Egypt.
EM abdofoda@mans.edu.eg
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1313
EP 1318
DI 10.1007/s12253-019-00704-2
PG 6
ER
PT J
AU Li, T
Li, H
Xie, Sh
Tan, Y
Xie, ZP
Li, WY
Ai, F
AF Li, Tao
Li, Heng
Xie, Sheng
Tan, Yan
Xie, Zi-Ping
Li, Wen-Yi
Ai, Fen
TI Lactate Dehydrogenase-to-Lymphocyte Ratio Represents a Powerful Prognostic Tool of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE International metastatic renal cell carcinoma database consortium; Metastatic renal cell carcinoma; Lactate dehydrogenase to lymphocytes ratio; Tyrosine kinase inhibitors; Prognostic factors
ID International metastatic renal cell carcinoma database consortium; Metastatic renal cell carcinoma; Lactate dehydrogenase to lymphocytes ratio; Tyrosine kinase inhibitors; Prognostic factors
AB Inflammation parameters were verified to predict clinical outcomes of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). Here, we developed a novel marker, lactate dehydrogenase (tumor burden marker) to lymphocytes (inflammation marker) ratio (LLR), aimed to reveal the prognostic role of LLR for mRCC patients treated with TKIs. We collected clinical data of mRCC patients treated with TKIs. Receiver operating curve analysis was used to determine the optimal cut-off value. The c-index method was used to determine the best predictive marker for overall survival (OS). Clinicopathological characteristics on OS and progression-free survival (PFS) were evaluated by univariate analysis, and multivariate analyses. LLR provided the greatest improvement in the c-index, and displayed the best marker of the prognostic accuracy for OS. Univariate analysis revealed that LLR, ECOG PS and IMDC risks were significant predictors of OS and PFS. However, multivariate analysis indicated that IMDC risks failed to predict PFS, and only showed predictor of OS. We finally stratified patients into low LLR (<150) and high LLR (≥150) group with different clinical outcomes. LLR represents a powerful prognostic tool of clinical outcome in mRCC patients treated with TKIs.
C1 [Li, Tao] Hubei University of Medicine, Remin HospitalShiyan, Hubei Province, China.
[Li, Heng] Hubei University of Medicine, Remin HospitalShiyan, Hubei Province, China.
[Xie, Sheng] Hubei University of Medicine, Remin HospitalShiyan, Hubei Province, China.
[Tan, Yan] Hubei University of Medicine, Remin HospitalShiyan, Hubei Province, China.
[Xie, Zi-Ping] Hubei University of Medicine, Remin HospitalShiyan, Hubei Province, China.
[Li, Wen-Yi] The First Affiliated Hospital of Kunming Medical CollegeKunming, Yunnan Province, China.
[Ai, Fen] Huazhong University of Science and Technology, Tongji Medical College, The Central Hospital of Wuhan, Department of EmergencyWuhan, Hubei Province, China.
RP Li, WY (reprint author), The First Affiliated Hospital of Kunming Medical College, Kunming, China.
EM 942408619@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1319
EP 1324
DI 10.1007/s12253-019-00707-z
PG 6
ER
PT J
AU Gallarin Salamanca, MI
Espin Jaime, TM
Moran-Penco, MJ
Salas Martinez, J
AF Gallarin Salamanca, Maria Isabel
Espin Jaime, Teresa Maria
Moran-Penco, Miguel Jose
Salas Martinez, Jesus
TI Role of Peritoneal Cytology in Patients with Early Stage Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Peritoneal lavage; Peritoneal cytology
ID Colorectal cancer; Peritoneal lavage; Peritoneal cytology
AB The main objective of this study was to investigate the incidence of free tumour cells in peritoneal lavage cytology performed using a standard method before and after the resection of the tumour, and to assess the usefulness of this technique in scheduled interventions on colorectal cancer patients. Peritoneal lavage cytology was performed on a homogeneous sample of 188 patients undergoing colorectal cancer curative resection before and after the resection of the tumour. The procedure was performed systematically in all cases. Malignant cells were detected in the peritoneal lavage cytology performed before the resection of the tumour in three patients. Lymph node affection was the variable most associated with the prognosis of these colorectal cancer patients. Peritoneal lavage cytology can provide additional information for a small group of patients who need to be closely monitored and studied to decide on the most effective type of chemotherapy.
C1 [Gallarin Salamanca, Maria Isabel] Infanta Cristina Hospital, Department of Surgery, Carrillo Areanas 20A. Villafranca de los Barros, 06220 Badajoz, Spain.
[Espin Jaime, Teresa Maria] Infanta Cristina Hospital, Department of Surgery, Carrillo Areanas 20A. Villafranca de los Barros, 06220 Badajoz, Spain.
[Moran-Penco, Miguel Jose] University of Extremadura, Department of SurgeryBadajoz, Spain.
[Salas Martinez, Jesus] Infanta Cristina Hospital, Department of Surgery, Carrillo Areanas 20A. Villafranca de los Barros, 06220 Badajoz, Spain.
RP Gallarin Salamanca, MI (reprint author), Infanta Cristina Hospital, Department of Surgery, 06220 Badajoz, Spain.
EM gallarinsa@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1325
EP 1329
DI 10.1007/s12253-019-00706-0
PG 5
ER
PT J
AU Lei, Y
Hu, Q
Gu, J
AF Lei, Yu
Hu, Qiaoling
Gu, Jiang
TI Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ChREBP; Glucose transporters; Hepatocellular carcinoma; Diagnostic marker; Glycolysis
ID ChREBP; Glucose transporters; Hepatocellular carcinoma; Diagnostic marker; Glycolysis
AB Carbohydrate response element binding protein (ChREBP) is a glucose-sensing transcription factor that mediates the induction of glycolytic and lipogenic genes in response to glucose. We investigated the expression patterns of ChREBP and glucose transporters (GLUTs) in human hepatocellular carcinoma (HCC) and their association with HCC progression. ChREBP, GLUT2 and GLUT1 immunohistochemistry were performed on liver tissue array containing normal liver tissue, HCC adjacent tissue and cancer tissue of different HCC stages. The effect of HCC malignancy on protein expression was analyzed with one-way ANOVA. The correlations between protein expressions were analyzed with Pearson Correlation test. We found that ChREBP protein expression tended to be positively correlated to liver malignancy. GLUT2 protein expression was significantly reduced in human HCC as compared to normal liver tissue and its expression in HCC was inversely associated to malignancy (p < 0.001). In contrast, GLUT1 was significantly increased in cancer cells and its expression was positively correlated to malignancy (p < 0.001). Furthermore, GLUT1 expression was positively associated to ChREBP expression (r = 0.481, p < 0.0001, n = 70) but negatively correlated to GLUT2 expression (r = −0.320, p = 0.007, n = 70). Notably, ChREBP-expressing hepatocytes did not express GLUT2 but GLUT1. This is the first report unveiling expressions of ChREBP and GLUT2/GLUT1 and their relations in HCC. The expression patterns are related to malignancy and this information would facilitate evaluation of clinical behavior and treatment of HCC.
C1 [Lei, Yu] Shantou University Medical College, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Department of Pathology and Pathophysiology, 515041 Shantou, Guangdong, China.
[Hu, Qiaoling] Shantou University Medical College, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Department of Pathology and Pathophysiology, 515041 Shantou, Guangdong, China.
[Gu, Jiang] Shantou University Medical College, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Department of Pathology and Pathophysiology, 515041 Shantou, Guangdong, China.
RP Gu, J (reprint author), Shantou University Medical College, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Department of Pathology and Pathophysiology, 515041 Shantou, China.
EM 2523381625@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1331
EP 1340
DI 10.1007/s12253-019-00708-y
PG 10
ER
PT J
AU Chauhan, Sh
Sen, S
Singh, N
Sharma, A
Chawla, B
Kashyap, S
AF Chauhan, Sheetal
Sen, Seema
Singh, Neeta
Sharma, Anjana
Chawla, Bhavna
Kashyap, Seema
TI Human Papillomavirus Detection Strategies in Retinoblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Chauhan, Sheetal] All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Ocular Pathology, Room no. 725, 110029 New Delhi, India.
[Sen, Seema] All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Ocular Pathology, Room no. 725, 110029 New Delhi, India.
[Singh, Neeta] All India Institute of Medical Sciences, Department of Biochemistry, 110029 New Delhi, India.
[Sharma, Anjana] All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Ocular Microbiology, 110029 New Delhi, India.
[Chawla, Bhavna] All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Ocular Oncology Service, 110029 New Delhi, India.
[Kashyap, Seema] All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Ocular Pathology, Room no. 725, 110029 New Delhi, India.
RP Sen, S (reprint author), All India Institute of Medical Sciences, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Ocular Pathology, 110029 New Delhi, India.
EM ssenop@rediffmail.com
CR OrjuelaM, Castaneda VP, Ridaura C, Lecona E, Leal C, Abramson DH, Orlow I, Gerald W, Cordon-Cardo C, 2000, Presence of human papilloma virus in tumor tissue from children with retinoblastoma: an alternative mechanism for tumor development. Clin Cancer Res 6:4010–4016
Montoya-Fuentes H, de la Paz Ramirez-Munoz M, Villar-Calvo V et al, 2003, Identification of DNA sequences and viral proteins of 6 human papillomavirus types in retinoblastoma tissue. Anticancer Res 23:2853–2862
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Antoneli CB, Ribeiro KB, Sredni STet al, 2011, Low prevalence of HPV in Brazilian children with retinoblastoma. J Med Virol 83: 115–118
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Ryoo NK, KimJE, Choung HK, KimN, Lee MJ,Khwarg SI, 2013, Human papilloma virus in retinoblastoma tissues from Korean patients. Korean J Ophthalmol 27:368–371
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1341
EP 1344
DI 10.1007/s12253-018-00577-x
PG 4
ER
PT J
AU Mo, YH
Jeon, HE
Kim, SM
Yoo, JN
Lee, HS
AF Mo, Yoon Ha
Jeon, Ha Eun
Kim, Sung Min
Yoo, Jin Nam
Lee, Hyung Sug
TI Analysis of Promoter Mutation in Long Non-coding RNA NEAT1 in Acute Leukemias
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mo, Yoon Ha] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Jeon, Ha Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Kim, Sung Min] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Huarte M, 2015, The emerging role of lncRNAs in cancer. Nat Med 21:1253–1261
Fang J, Qiao F, Tu J, Xu J, Ding F, Liu Y, Akuo BA, Hu J, Shao S, 2017, High expression of long non-coding RNA NEAT1 indicates poor prognosis of human cancer. Oncotarget 8:45918–45927
Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G, 2017, Recurrent and functional regulatory mutations in breast cancer. Nature 547:55–60
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1345
EP 1346
DI 10.1007/s12253-019-00608-1
PG 2
ER
PT J
AU Tsiambas, E
Mastronikolis, SN
Fotiades, PP
Ragos, V
Kavantzas, N
Lazaris, CA
AF Tsiambas, Evangelos
Mastronikolis, S Nicholas
Fotiades, P Panagiotis
Ragos, Vasileios
Kavantzas, Nikolaos
Lazaris, C Andreas
TI Epstein-Barr Virus MicroRNAs in Nasopharyngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Tsiambas, Evangelos] 401 General Army Hospital, Department of Pathology-CytologyAthens, Greece.
[Mastronikolis, S Nicholas] 401 General Army Hospital, Department of Pathology-CytologyAthens, Greece.
[Fotiades, P Panagiotis] 424 General Army Hospital, Department of SurgeryThessaloniki, Greece.
[Ragos, Vasileios] University of Ioannina, School of Health Sciences, Department of Maxillofacial and Department of MedicineIoannina, Greece.
[Kavantzas, Nikolaos] University of Athens, Medical School, Department of PathologyAthens, Greece.
[Lazaris, C Andreas] University of Athens, Medical School, Department of PathologyAthens, Greece.
RP Tsiambas, E (reprint author), 401 General Army Hospital, Department of Pathology-Cytology, Athens, Greece.
EM tsiambasecyto@yahoo.gr
CR Lo KW, Chung GT, To KF, 2012, Deciphering themolecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 22:79–86
Hiromu S, Maruyama R, Yamamoto E, Masahiro K, 2012, DNA methylation and microRNA dysregulation in cancer. Mol Oncol 6: 567–578
Zhao L, Fong AHW, Liu N, Cho WCS, 2018, Molecular subtyping of nasopharyngeal carcinoma, NPC, and a microRNA-based prognostic model for distant metastasis. J Biomed Sci 25(1):16–28
Wu Q, Han T, Sheng X, ZhangN,Wang P, 2018)Downregulation of EB virus miR-BART4 inhibits proliferation and aggressiveness while promoting radiosensitivity of nasopharyngeal carcinoma. Biomed Pharmacother 108:741–751
Lung RW, Hau PM, Yu KH et al, 2018, EBV-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma. J Pathol 244(4):394–407
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1347
EP 1348
DI 10.1007/s12253-019-00631-2
PG 2
ER
PT J
AU Pinczes, L
Magyari, F
Remenyi, Gy
Pfliegler, Gy
Barna, S
Bedekovics, J
Illes,
AF Pinczes, Laszlo
Magyari, Ferenc
Remenyi, Gyula
Pfliegler, Gyorgy
Barna, Sandor
Bedekovics, Judit
Illes, Arpad
TI Intravascular Occlusion by Leukemic Blast Cells Causing Multiplex Hand Necrosis in a Patient with Acute Myeloid Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Pinczes, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Magyari, Ferenc] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Remenyi, Gyula] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Pfliegler, Gyorgy] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Barna, Sandor] Scanomed Kft.Debrecen, Hungary.
[Bedekovics, Judit] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Pinczes, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM pinczes.laszlo.imre@med.unideb.hu
CR Yamamoto Y, Yamamoto S, 2017, Achenbach’s Syndrome. N Engl J Med 376:e53. , DOI 10.1056/NEJMicm1610146
Guzman-Uribe P, Vargas-Ruiz AG, 2015, Thrombosis in leukemia: incidence, causes, and practical management. Curr Oncol Rep 17:19. , DOI 10.1007/s11912-015-0444-2
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1349
EP 1351
DI 10.1007/s12253-019-00636-x
PG 3
ER
PT J
AU Kumar, SS
Sreedharan, NS
Patil, Sh
Raj, Th
AF Kumar, Satish Sunil
Sreedharan, Nellimad Sreena
Patil, Shankargouda
Raj, A. Thirumal
TI The Potential Role of Organoids in Pathology and Oncology Research
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Kumar, Satish Sunil] Sai Srinivas Dental Care, SithalapakkamChennai, India.
[Sreedharan, Nellimad Sreena] Corning Dental AssociatesCorning, NY, USA.
[Patil, Shankargouda] Jazan University, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral PathologyJazan, Saudi Arabia.
[Raj, A. Thirumal] Sri Venkateswara Dental College and Hospital, Department of Oral Pathology and Microbiology, Thalambur, 600130 Chennai, India.
RP Raj, Th (reprint author), Sri Venkateswara Dental College and Hospital, Department of Oral Pathology and Microbiology, 600130 Chennai, India.
EM thirumalraj666@gmail.com
CR LancasterMA, Knoblich JA, 2014, Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345(6194):1247125. , DOI 10.1126/science.1247125
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Duong HQ, Nemazanyy I, Rambow F, Tang SC, Delaunay S, Tharun L, Florin A, Buttner R, Vandaele D, Close P, Marine JC, Shostak K, ChariotA(2018, The endosomal protein CEMIP linksWnt signaling to MEK1-ERK1/2 activation in Selumetinib-resistant intestinal organoids. Cancer Res 78:4533–4548. , DOI 10.1158/ 0008-5472.CAN-17-3149
Ullah I, Subbarao RB, Rho GJ, 2015, Human mesenchymal stem cells - current trends and future prospective. Biosci Rep 35(2): e00191. , DOI 10.1042/BSR20150025
Jabs J, Zickgraf FM, Park J, Wagner S, Jiang X, Jechow K, Kleinheinz K, Toprak UH, Schneider MA, Meister M, Spaich S, Sutterlin M, Schlesner M, Trumpp A, Sprick M, Eils R, Conrad C, 2017, Screening drug effects in patient-derived cancer cells link organoid responses to genome alterations. Mol Syst Biol 13:955. , DOI 10.15252/msb.20177697
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1353
EP 1354
DI 10.1007/s12253-019-00642-z
PG 2
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Immune Checkpoint Inhibitors in Small Cell Lung Cancer: Is It Also a Matter of Helios− Cells?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG, Spigel DR, Moreno V, Chau I, Hann CL, Eder JP, Steele NL, Pieters A, Fairchild J, Antonia SJ, 2018, Third-line nivolumab monotherapy in recurrent sclc: check mate 032. J Thorac Oncol. 2018 Oct 10. pii: S1556–0864(18)33181–2.0998079
Schmid S, Fruh M, 2018, Immune checkpoint inhibitors and small cell lung cancer: what's new? Thorac Dis 2018 May;10(Suppl 13): S1503–S1508
Wang W, Hodkinson P, McLaren F, MacKinnon A, Wallace W, Howie S, Sethi T, 2012 Sep 15, Small cell lung cancer tumour cells induce regulatory T lymphocytes, and patient survival correlates negatively with FOXP3+ cells in tumour infiltrate. Int J Cancer 131(6):E928–E937
Himmel ME1, MacDonald KG, Garcia RV, Steiner TS, Levings MK. Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans. J Immunol 2013 Mar 1;190(5):2001–2008
Zhang X, Zeng Y, Qu Q, Zhu J, Liu Z, Ning W, Zeng H, Zhang N, DuW, Chen C, Huang JA, 2017 Dec, PD-L1 induced by IFN-γ from tumor-associated macrophages via the JAK/STAT3 and PI3K/AKT signaling pathways promoted progression of lung cancer. Int J Clin Oncol 22(6):1026–1033
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1355
EP 1356
DI 10.1007/s12253-019-00653-w
PG 2
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Immune Checkpoint Inhibitor Therapy in HIV-Positive Patients with Advanced-Stage Cancer: a Golden Card to Be Played?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Cook MR, Kim C, 2019, Safety and efficacy of immune checkpoint inhibitor therapy in patients with HIVinfection and advancedstage Cancer: a systematic review. JAMA Oncol. , DOI 10. 1001/jamaoncol.2018.6737
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Rachakonda S, Srinivas N, Mahmoudpour SH, Garcia-Casado Z, Requena C, TravesV, SorianoV, CardelliM, Pjanova D,Molven A, Gruis N, Nagore E, Kumar R, 2018, Telomere length and survival in primary cutaneous melanoma patients. Sci Rep 8(1):10947
Unemori P, Leslie KS, HuntPW, Sinclair E, Epling L,Mitsuyasu R, Effros RB, Dock J, Dollard SG, Deeks SG, Martin JN, Maurer TA, 2013, Immunosenescence is associated with presence of Kaposi's sarcoma in antiretroviral treated HIV infection. AIDS. 27(11):1735
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Lichterfeld M,Mou D, Cung TD,WilliamsKL,WaringMT, Huang J, Pereyra F, Trocha A, Freeman GJ, Rosenberg ES,Walker BD, Yu XG, 2008, Telomerase activity of HIV-1-specific CD8+ T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors. Blood. 112(9):3679–3687
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Aamdal E, Gaudernack G, Inderberg EM, Rasch W, Bjorheim J, Aamdal S, Guren TK, 2017, Telomerase peptide vaccine combined with ipilimumab in metastatic melanoma: reports from a phase I trial. Ann Oncol Volume 28(Issue suppl_5):1
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1357
EP 1358
DI 10.1007/s12253-019-00686-1
PG 2
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Body Fat and Risk of Breast Cancer in Postmenopausal Women: What Is the Truth?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L, Cheng TD, Feliciano EC, Lane D, Luo J, Nassir R, Pan K, Wassertheil-Smoller S, Kamensky V, Rohan TE, Dannenberg AJ, 2018, Association of body fat and risk of breast cancer in postmenopausal women with normal body mass index: a secondary analysis of a randomized clinical trial and observational study. JAMA Oncol 5:155. , DOI 10.1001/jamaoncol.2018.5327
Gomes JL, Fernandes T, Soci UP, Silveira AC, Barretti DL, Negrao CE, Oliveira EM, 2017, Obesity downregulates MicroRNA-126 inducing capillary rarefaction in skeletal muscle: effects of aerobic exercise training. Oxidative Med Cell Longev 2017:2415246
Wang CZ, Yuan P, Li Y, 2015 Jun 1, MiR-126 regulated breast cancer cell invasion by targeting ADAM9. Int J Clin Exp Pathol 8(6):6547–6553
Li P,Wei J, Li X, Cheng Y, ChenW, Cui Y, Simoncini T, Gu Z, Yang J, Fu X, 2017, 17β-estradiol enhances vascular endothelial Ets-1/ miR-126-3p expression: the possible mechanism for attenuation of atherosclerosis. J Clin Endocrinol Metab 102(2):594–603
Furlan A, Vercamer C, Heliot L, Wernert N, Desbiens X, Pourtier A, 2019, Ets-1 drives breast cancer cell angiogenic potential and interactions between breast cancer and endothelial cells. Int J Oncol 54(1):29–40
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1359
EP 1360
DI 10.1007/s12253-019-00691-4
PG 2
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Total Serum Cholesterol and Pancreatic Cancer Risk: What Is the Link?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Chen WC, Boursi B, Mamtani R, Yang YX, 2018, Total serum cholesterol and pancreatic cancer: a nested case-control study. Cancer Epidemiol Biomark Prev 28(2):363-369
Zhou P, Li B, Liu B, Chen T, Xiao J, 2018, Prognostic role of serum total cholesterol and high-density lipoprotein cholesterol in cancer survivors: a systematic review and meta-analysis. Clin Chim Acta 477:94–104
Razidlo GL, Burton KM, McNiven MA, 2018, Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42. J Biol Chem 293(28):11143–11153
Holmer R, Goumas FA,Waetzig GH, Rose-John S, Kalthoff H, 2014, Interleukin-6: a villain in the drama of pancreatic cancer development and progression. Hepatobiliary Pancreat Dis Int 13(4):371–380
Hashizume M, Mihara M, 2011, IL-6 and lipid metabolism. Inflammation and Regeneration 31:325–333
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1361
EP 1361
DI 10.1007/s12253-019-00698-x
PG 1
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Aspirin Use and Risk of Glioma: a Double Track for a Single Goal?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Gusyatiner O, Hegi ME, 2018 Aug, Glioma epigenetics: from subclassification to novel treatment options. Semin Cancer Biol 51:50– 58
Amirian ES, Ostrom QT, Armstrong GN, Lai RK, Gu X, Jacobs DI, Jalali A, Claus EB, Barnholtz-Sloan JS, Il'yasova D, Schildkraut JM, Ali-Osman F, Sadetzki S, Jenkins RB, LaChance DH, Olson SH, Bernstein JL, Merrell RT, Wrensch MR, Johansen C, Houlston RS, ScheurerME, Shete S,Amos CI, Melin B, BondyML, 2018 Nov 27. pii: cebp.0702.2018, Aspirin, non-steroidal anti-inflammatory drugs, NSAIDs), and glioma risk: original data from the glioma international case-control study and a meta-analysis. Cancer Epidemiol Biomark Prev. , DOI 10.1158/1055-9965.EPI-18-0702
Fujita M, Kohanbash G, Fellows-MayleW,Hamilton RL, Komohara Y, Decker SA, Ohlfest JR, Okada H, 2011 Apr 1, COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71(7):2664–2674
Zhang S, Zhang C, Song Y, Zhang J, Xu J, 2018, Prognostic role of survivin in patients with glioma.Medicine, Baltimore, 97(17):e0571
Zhang F, Chu J,Wang F, 2017, Expression and clinical significance of cyclooxygenase 2 and survivin in human gliomas. Oncol Lett 14(2):1303–1308
Nemeth K, Szucs N, Czirjak S, Reiniger L, Szabo B, Barna G, Karaszi K, Igaz P, Zivkovic V, Korbonits M, Patocs A, Butz H, 2018, Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas. Oncotarget. 9(49):29180–29192
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1363
EP 1364
DI 10.1007/s12253-019-00699-w
PG 2
ER
PT J
AU Mormile, R
AF Mormile, Raffaella
TI Statin Therapy and Survival among Women with Ovarian Cancer: how much of it Is True?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mormile, Raffaella] Moscati Hospital, Division of Pediatrics and Neonatology, Via A. Gramsci, 81031 Aversa, Italy.
RP Mormile, R (reprint author), Moscati Hospital, Division of Pediatrics and Neonatology, 81031 Aversa, Italy.
EM raffaellamormile@alice.it
CR Harding BN, Delaney JA, Urban RR, Weiss NS, 2019, Use of statinmedications following diagnosis in relation to survival among women with ovarian cancer. Cancer Epidemiol Biomark Prev 28: 1127–1133
Couttenier A, Lacroix O, Vaes E, Cardwell CR, De Schutter H, Robert A, 2017, Statin use is associated with improved survival in ovarian cancer: a retrospective population-based study. PLoS One 12(12):e0189233
Loppnow H, Zhang L, Buerke M, Lautenschlager M, Chen L, Frister A, Schlitt A, Luther T, Song N, Hofmann B, Rose-John S, Silber RE, Muller-Werdan U, Werdan K, 2011, Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC co cultures. J Cell Mol Med 15(4):994–1004
Hansen M, Kuhlman ACB, Sahl RE, Kelly B, Morville T, Dohlmann TL, Chrois KM, Larsen S, Helge JW, Dela F, 2019, Inflammatory biomarkers in patients in Simvastatin treatment: No effect of co-enzyme Q10 supplementation. Cytokine 113:393–399. , DOI 10.1016/j.cyto.2018.10.011
Davaro F, Forde SD, Garfield M, Jiang Z, Halmen K, Tamburro ND, Kurt-Jones E, Fitzgerald KA, Golenbock DT, Wang D, 2014, 3-Hydroxyl-3-methylglutaryl coenzyme a, HMG-CoA, reductase inhibitor, statin)-induced 28-kDa interleukin-1β interfereswithmature IL-1β signaling. J Biol Chem 289(23):16214–16222
Cahill CM, Rogers JT, 2008, Interleukin, IL, 1beta induction of IL- 6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1. J Biol Chem 283(38):25900–25912
Schauer IG, Zhang J, Xing Z, Guo X, Mercado-Uribe I, Sood AK, Huang P, Liu J, 2013, Interleukin-1β promotes ovarian tumorigenesis through a p53/NF-κB-mediated inflammatory response in stromal fibroblasts. Neoplasia 15(4):409–420
Browning L, Patel MR, Horvath EB, Tawara K, Jorcyk CL, 2018, IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res 10:6685–6693
Yousefi H, Momeny M, Ghaffari SH, Parsanejad N, Poursheikhani A, Javadikooshesh S, Zarrinrad G, Esmaeili F, Alishahi Z, Sabourinejad Z, Sankanian G, Shamsaiegahkani S, Bashash D, Shahsavani N, Tavakkoly-Bazzaz J, Alimoghaddam K, Ghavamzadeh A, 2019, IL-6/IL-6R pathway is a therapeutic target in chemoresistant ovarian cancer. Tumori 105(1):84–91. https://doi. org/10.1177/0300891618784790
Samavati L, Rastogi R, Du W, Huttemann M, Fite A, Franchi L, 2009, STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria. Mol Immunol 46(8–9):1867–1877
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAY
PY 2020
VL 26
IS 2
BP 1365
EP 1366
DI 10.1007/s12253-019-00729-7
PG 2
ER
PT J
AU Lu, ChTh
Collins, L
Cohen, P
Jay, A
Campbell, MJ
O’Callaghan, M
AF Lu, Chengxuan Thomas
Collins, Luke
Cohen, Penelope
Jay, Alex
Campbell, M Jared
O’Callaghan, Michael
TI Prognostic Differences in ISUP Grade Group 4: a Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Prostate cancer; Gleason score; Grade group 4; Biopsy; Prostate cancer specific mortality
ID Prostate cancer; Gleason score; Grade group 4; Biopsy; Prostate cancer specific mortality
AB The ISUP (Internal Society of Urologic Pathology) recently adopted a five-tiered prognostication system. There is evidence to suggest that the ISUP grade group 4 is a heterogeneous entity regarding prognosis. Our aim was to systematically examine the existing evidence to determine if outcome differences exist within the ISUP grade group 4. A systematic search of the literature for all studies examining the heterogeneity of the ISUP grade group 4 was conducted. Available studies were combined with meta-analysis to evaluate prognostic differences within the ISUP grade group 4 measured by all cause mortality (ACM) and the prostate cancer-specific mortality (PCSM). Eight studies were identified and utilised a variety of outcome measures to answer the question of heterogeneity within the ISUP grade group 4. Four of these studies examined prognosis using both ACM and PCSM. These were combined into a meta-analysis. The combined group of 5 + 3/3 + 5 had statistically significant higher ACM (hazard ratio [HR] 1.23, 95% confidence internal [Cl] 1.08–1.41) when compared to the 4+4 group. There was no difference in the PCSM between the two groups (HR 1.34, 95% CI 0.89–2.01). However, heterogeneity was high for this analysis secondary to a range of methodological differences. Our meta-analysis showed that Gleason grade 3 + 5/5 + 3 had higher ACM than Gleason grade group 4 + 4. Measures of PCSM were statistically insignificant, although heterogeneity was high. Evidence suggests that heterogeneity is likely, although inconclusive. Further studies with consistent methodologies are required to answer this question.
C1 [Lu, Chengxuan Thomas] UNSW, The George Institute for Global Health, 2052 Sydney, NSW, Australia.
[Collins, Luke] Royal Adelaide Hospital, 5000 Adelaide, Australia.
[Cohen, Penelope] Royal Adelaide Hospital, SA PathologyAdelaide, Australia.
[Jay, Alex] Flinders Medical Centre, Urology Unit, Bedford ParkAdelaide, Australia.
[Campbell, M Jared] UNSW, Graduate School of Biomedical Engineering, Centre for Nanoscale Biophotonics, 2052 Sydney, NSW, Australia.
[O’Callaghan, Michael] Flinders Medical Centre, Urology Unit, Bedford ParkAdelaide, Australia.
RP Lu, ChTh (reprint author), UNSW, The George Institute for Global Health, 2052 Sydney, Australia.
EM thomascxlu@gmail.com
CR Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV, Nelson JB, Rodrigues G, Sandler HM, Taplin ME, Treadwell JR, 2017, Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part I: risk stratification, shared decision making, and care options. J Urol 199:683–690. , DOI 10.1016/j.juro. 2017.11.095
Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV, Nelson JB, Rodrigues G, Sandler HM, Taplin ME, Treadwell JR, 2018, Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part II: recommended approaches and details of specific care options. J Urol 199(4):990–997. , DOI 10.1016/j.juro. 2018.01.002
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL, 2005, The 2005 International Society of Urological Pathology, ISUP, consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 29(9):1228–1242
(NCCN, NCCN, 2018, Clinical practice guidelines on prostate cancer
Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi- Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA,Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA, 2016, A contemporary prostate Cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3): 428–435. , DOI 10.1016/j.eururo.2015.06.046
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Kang DE, Fitzsimons NJ, Presti JC Jr, Kane CJ, Terris MK, Aronson WJ, Amling CL, Freedland SJ, Group SDS, 2007, Risk stratification of men with Gleason score 7 to 10 tumors by primary and secondary Gleason score: results from the SEARCH database. Urology 70(2):277–282. , DOI 10.1016/j.urology.2007.03.059
Koontz BF, TsivianM, Mouraviev V, Sun L, Vujaskovic Z,Moul J, LeeWR, 2012, Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers. Int J Radiat Oncol Biol Phys 82(1):200–203. , DOI 10.1016/j.ijrobp.2010.11.023
Stark JR, Perner S, StampferMJ, Sinnott JA, Finn S, Eisenstein AS, Ma J, Fiorentino M, Kurth T, LodaM, Giovannucci EL, RubinMA, Mucci LA, 2009, Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol 27(21):3459–3464. , DOI 10.1200/ jco.2008.20.4669
Tollefson MK, Leibovich BC, Slezak JM, Zincke H, Blute ML, 2006, Long-term prognostic significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer: impact on prostate cancer specific survival. J Urol 175(2):547– 551. , DOI 10.1016/s0022-5347(05)00152-7
Wright JL, Salinas CA, Lin DW, Kolb S, Koopmeiners J, Feng Z, Stanford JL, 2009, Prostate cancer specific mortality and Gleason 7 disease differences in prostate cancer outcomes between cases with Gleason 4 + 3 and Gleason 3 + 4 tumors in a population based cohort. J Urol 182(6):2702–2707. , DOI 10.1016/j.juro. 2009.08.026
Huynh MA, Chen MH, Wu J, Braccioforte MH, Moran BJ, D'Amico AV, 2016, Gleason score 3 + 5 or 5 + 3 versus 4 + 4 prostate cancer: the risk of death. Eur Urol 69(6):976– 979. , DOI 10.1016/j.eururo.2015.08.054
Mahal BA, Muralidhar V, Chen YW, Choueiri TK, Hoffman KE, Hu JC, Sweeney CJ, Yu JB, Feng FY, Trinh QD, Nguyen PL, 2016, Gleason score 5 + 3 = 8 prostate cancer: much more like Gleason score 9? BJU Int 118(1):95–101. , DOI 10.1111/bju.13239
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1367
EP 1375
DI 10.1007/s12253-019-00632-1
PG 9
ER
PT J
AU Raffone, A
Travaglino, A
Saccone, G
D’Alessandro, P
Arduino, B
Mascolo, M
De Placido, G
Insabato, L
Zullo, F
AF Raffone, Antonio
Travaglino, Antonio
Saccone, Gabriele
D’Alessandro, Pietro
Arduino, Bruno
Mascolo, Massimo
De Placido, Giuseppe
Insabato, Luigi
Zullo, Fulvio
TI Diabetes Mellitus Is Associated with Occult Cancer in Endometrial Hyperplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Concurrent cancer; Endometrial cancer; Endometrial intraepithelial neoplasia; Glycemia; Occult cancer; Risk
ID Concurrent cancer; Endometrial cancer; Endometrial intraepithelial neoplasia; Glycemia; Occult cancer; Risk
AB In the management of women diagnosed with endometrial hyperplasia (EH), it is crucial to determine the risk of coexistent cancer. Diabetes mellitus has been recently suggested as a significant risk factor. However, results in this regard are conflicting. Our aim was to assess the association between diabetes mellitus and coexistent cancer in women diagnosed with endometrial hyperplasia. A systematic review and meta-analysis was performed by searching electronic databases from their inception to October 2018 for studies assessing the presence of coexistent cancer after a preoperative diagnosis of endometrial hyperplasia in women stratified for diabetes mellitus. Odds ratio was calculated with 95% confidence interval; a p value <0.05 was considered significant. Twelve retrospective studies with 1579 EH were included. Diabetes mellitus showed significant association with the presence of cancer coexistent with endometrial hyperplasia (OR = 1.96; 95% CI, 1.07–3.60; p = 0.03). Heterogeneity among studies was moderate (I2 = 55%). Funnel plot showed asymmetric distribution of OR values, with the large and accurate studies showing results stronger than small and less accurate one; this finding should exclude a publication bias. In women diagnosed with endometrial hyperplasia, diabetes mellitus is a risk factor for coexistent cancer, and thus may be included in a predictive algorithm for the risk stratification. In women conservatively treated, glycemic control may be required to prevent the risk of progression. Further studies are necessary to confirm the clinical significance of diabetes mellitus in this field.
C1 [Raffone, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Saccone, Gabriele] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[D’Alessandro, Pietro] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Arduino, Bruno] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Mascolo, Massimo] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[De Placido, Giuseppe] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Insabato, Luigi] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Zullo, Fulvio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
RP Travaglino, A (reprint author), University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, 80131 Naples, Italy.
EM antonio.travaglino.ap@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1377
EP 1384
DI 10.1007/s12253-019-00684-3
PG 8
ER
PT J
AU Wong, D
Yip, S
Sorensen, HP
AF Wong, Derek
Yip, Stephen
Sorensen, H Poul
TI Methods for Identifying Patients with Tropomyosin Receptor Kinase (TRK) Fusion Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NTRK gene fusions; TRK fusions; TRK inhibitors; Next-generation sequencing; NGS
ID NTRK gene fusions; TRK fusions; TRK inhibitors; Next-generation sequencing; NGS
AB NTRK gene fusions affecting the tropomyosin receptor kinase (TRK) protein family have been found to be oncogenic drivers in a broad range of cancers. Small molecule inhibitors targeting TRK activity, such as the recently Food and Drug Administration-approved agent larotrectinib (Vitrakvi®), have shown promising efficacy and safety data in the treatment of patients with TRK fusion cancers. NTRK gene fusions can be detected using several different approaches, including fluorescent in situ hybridization, reverse transcription polymerase chain reaction, immunohistochemistry, next-generation sequencing, and ribonucleic acid-based multiplexed assays. Identifying patients with cancers that harbor NTRK gene fusions will optimize treatment outcomes by providing targeted precision therapy.
C1 [Wong, Derek] University of British Columbia, Department of PathologyVancouver, BC, Canada.
[Yip, Stephen] University of British Columbia, Department of PathologyVancouver, BC, Canada.
[Sorensen, H Poul] Provincial Health Services Authority, British Columbia Cancer AgencyVancouver, BC, Canada.
RP Sorensen, HP (reprint author), Provincial Health Services Authority, British Columbia Cancer Agency, Vancouver, Canada.
EM psor@mail.ubc.ca
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1385
EP 1399
DI 10.1007/s12253-019-00685-2
PG 15
ER
PT J
AU Li, Z
Liu, J
Zhang, X
Fang, L
Zhang, C
Zhang, Z
Yan, L
Tang, Y
Fan, Y
AF Li, Zeyan
Liu, Jikai
Zhang, Xiang
Fang, Liang
Zhang, Cong
Zhang, Zhao
Yan, Lei
Tang, Yueqing
Fan, Yidong
TI Prognostic Significance of Cyclin D1 Expression in Renal Cell Carcinoma: a Systematic Review and Meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE CyclinD1; Renal cell carcinoma; Prognosis; Meta-analysis
ID CyclinD1; Renal cell carcinoma; Prognosis; Meta-analysis
AB Previous studies indicated that cyclin D1 shown the potential as a tumor biomarker. However, the prognostic value of cyclin D1 in renal cell carcinoma (RCC) remains controversial. This study investigated the correlation of cyclin D1 expression with the prognostic and clinicopathological features in RCC patients. We systematically searched the database of PubMed, Embase, Cochrane, and Web of Science updated on November 26, 2017. Eighteen studies with 2282 patients satisfied the inclusion criteria. Results demonstrated that cyclin D1 overexpression in RCC showed significant favorable prognostic impact on disease-free survival (DFS) (HR 0.57, 95% CI: 0.43–0.74) and disease-specific survival (DSS) (HR 0.59, 95% CI 0.41–0.85) without significant heterogeneity. In subgroup of clear cell RCC, the prognostic effect on DFS was robust and the pooled HR was 0.39 (95% CI: 0.27–0.57). However, no association between overall survival (OS) and cyclin D1 expression was observed. Stratified analysis in DFS studies by sample size, staining patterns race and metastasis status showed similar results. Otherwise, cyclin D1 overexpression predicted a reduced prevalence of high TNM stage (T3 + T4) (OR 0.63, 95% CI: 0.40–0.99), high-grade tumor (G3 + G4) (OR 0.51, 95% CI: 0.31–0.81) and large tumor size (OR 0.35, 95% CI: 0.19–0.62). Our meta-analysis indicated that cyclin D1 overexpression could predict the favorable prognosis in patients with RCC.
C1 [Li, Zeyan] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Liu, Jikai] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Zhang, Xiang] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Fang, Liang] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Zhang, Cong] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Zhang, Zhao] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Yan, Lei] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Tang, Yueqing] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
[Fan, Yidong] Qilu Hospital of Shandong University, Department of Urology, Wenhuaxi Road 44, 250012 Jinan, Shandong, China.
RP Fan, Y (reprint author), Qilu Hospital of Shandong University, Department of Urology, 250012 Jinan, China.
EM fanyd@sdu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1401
EP 1409
DI 10.1007/s12253-019-00776-0
PG 9
ER
PT J
AU Travaglino, A
Raffone, A
Mascolo, M
Guida, M
Insabato, L
Zannoni, FG
Zullo, F
AF Travaglino, Antonio
Raffone, Antonio
Mascolo, Massimo
Guida, Maurizio
Insabato, Luigi
Zannoni, Franco Gian
Zullo, Fulvio
TI TCGA Molecular Subgroups in Endometrial Undifferentiated/Dedifferentiated Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cancer; Treatment; Endometrium; Risk assessment; PROMISE
ID Cancer; Treatment; Endometrium; Risk assessment; PROMISE
AB We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53- wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/ DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6%for the p53abn subgroup, 25%for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/ DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma.
C1 [Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Raffone, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Mascolo, Massimo] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Guida, Maurizio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Insabato, Luigi] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Zannoni, Franco Gian] Catholic University of the Sacred Heart, Agostino Gemelli University Polyclinic, Pathology Unit, Department of Woman and Child HealthRome, Italy.
[Zullo, Fulvio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
RP Raffone, A (reprint author), University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, 80131 Naples, Italy.
EM anton.raffone@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1411
EP 1416
DI 10.1007/s12253-019-00784-0
PG 6
ER
PT J
AU Raffone, A
Travaglino, A
Cerbone, M
Gencarelli, A
Mollo, A
Insabato, L
Zullo, F
AF Raffone, Antonio
Travaglino, Antonio
Cerbone, Marco
Gencarelli, Annarita
Mollo, Antonio
Insabato, Luigi
Zullo, Fulvio
TI Diagnostic Accuracy of Immunohistochemistry for Mismatch Repair Proteins as Surrogate of Microsatellite Instability Molecular Testing in Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Mismatch repair; Microsatellite instability; Endometrial cancer; Risk assessment; ProMisE; TCGA
ID Mismatch repair; Microsatellite instability; Endometrial cancer; Risk assessment; ProMisE; TCGA
AB Microsatellite instability (MSI) defines one of the four molecular groups of endometrial carcinoma identified by The Cancer Genome Atlas (TCGA). Immunohistochemistry for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) has been proposed as a widely applicable technique to identify this group in the common practice. However, the diagnostic accuracy of such approach has never been calculated. We aimed to assess: 1) the diagnostic accuracy of MMR proteins immunohistochemistry as surrogate of MSI molecular testing in endometrial carcinoma; 2) whether a combination of only two MMR proteins may be used as a still cheaper test. A systematic review and meta-analysis of was performed by searching electronic databases from their inception to September 2019. All studies assessing endometrial carcinoma with bothMMR proteins immunohistochemistry and MSI molecular testing were included. Diagnostic accuracy was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves.A subgroup analysis was performed for a combination of only two MMR proteins (MLH1-MSH2 vs MSH6-PMS2). Ten studies with 3097 patients were included. Out of these, 1110 were suitable for the meta-analysis. Immunohistochemistry for all the four MMR proteins showed sensitivity = 0.96, specificity = 0.95, LR + =17.7, LR- = 0.05, DOR = 429.77, and high diagnostic accuracy (AUC = 0.988). The combination of MLH1 and MSH2 showed sensitivity = 0.88, specificity = 0.96, LR + =22.36, LR- = 0.15, DOR = 200.69, and high diagnostic accuracy (AUC = 0.9838). The combination of MSH6 and PMS2 showed the same results as the complete panel of four MMR proteins. In conclusion, MMR proteins immunohistochemistry is a highly accurate surrogate of MSI molecular testing in endometrial carcinoma. A combination of MSH6 and PMS2 may allow reducing the cost without decrease in the diagnostic accuracy.
C1 [Raffone, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Cerbone, Marco] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
[Gencarelli, Annarita] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Mollo, Antonio] University of Salerno, Surgery and Dentistry “Scuola Medica Salernitana”, Department of MedicineSalerno, Baronissi, Italy.
[Insabato, Luigi] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Zullo, Fulvio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics UnitNaples, Italy.
RP Travaglino, A (reprint author), University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, 80131 Naples, Italy.
EM antonio.travaglino@unina.it
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1417
EP 1427
DI 10.1007/s12253-020-00811-5
PG 11
ER
PT J
AU Uhlyarik, A
Piurko, V
Vizkeleti, L
Papai, Zs
Raso, E
Lahm, E
Kiss,
Sikter, M
Vachaja, J
Kenessey, I
Timar, J
AF Uhlyarik, Andrea
Piurko, Violetta
Vizkeleti, Laura
Papai, Zsuzsanna
Raso, Erzsebet
Lahm, Erika
Kiss, Eva
Sikter, Marta
Vachaja, Jozsef
Kenessey, Istvan
Timar, Jozsef
TI EGFR Protein Expression of KRAS Wild-Type Colorectal Cancer: Predictive Value of the Sidedness for Efficacy of Anti-EGFR Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancer; EGFR protein; Sidedness; Anti-EGFR therapy
ID Colon cancer; EGFR protein; Sidedness; Anti-EGFR therapy
AB Right- and left-sided colorectal cancers (RSCRC and LSCRC, respectively) are different developmentally, genetically and prognostically. Clinical data also indicate that they respond differently to anti-EGFR therapies. The role of EGFR protein expression in KRAS wild type colorectal cancer is also controversial. Here we have used a cohort of anti-EGFR antibody treated KRAS-wild type colorectal cancer patients (n = 97) to analyse the prognostic role of EGFR protein expression in relation to sidedness. In our cohort EGFR copy number, determined by FISH, was not associated with the level of EGFR protein, assessed by immunohistochemistry and measured by H-scoring. There was a significantly higher EGFR H-score detected in RSCRC as compared to LSCRC in primary tumors (p = 0.04). Furthermore, in a proportion of cases (n = 31) metastatic tissues were also available and their analysis also found a significantly higher EGFR H-score in metastases of RSCRC compared to LSCRC (p = 0.018). Kaplan Meyer survival analysis demonstrated that anti-EGFR antibody therapies were more effective in case of LSCRC compared to RSCRC. Although in case of progression-free survival data just indicated a trend (p = 0.065), in case of overall survival the difference was significant favouring LSCRC (p = 0.047). These data demonstrated for the first time that the EGFR protein expression is significantly higher in KRAS wild type RSLCL as compared to LSCRC. Meanwhile it is somewhat unexpected that the lower EGFR protein expression was found to be associated with better efficacy of anti-EGFR antibody therapies of colorectal cancer, the finding of which must be further validated.
C1 [Uhlyarik, Andrea] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Piurko, Violetta] Semmelweis University, 2nd Department of Pathology, 93 Ulloi str, 1091 Budapest, Hungary.
[Vizkeleti, Laura] Semmelweis University, 2nd Department of Pathology, 93 Ulloi str, 1091 Budapest, Hungary.
[Papai, Zsuzsanna] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, 93 Ulloi str, 1091 Budapest, Hungary.
[Lahm, Erika] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Kiss, Eva] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Sikter, Marta] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Vachaja, Jozsef] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of Pathology, 93 Ulloi str, 1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, 93 Ulloi str, 1091 Budapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM jtimar@gmail.com
CR Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P, Passalacqua R, Sgroi G, Barni S, 2017, Prognostic survival associated with left-sided vs right-sided colon cancer: a systematic review and meta-analysis. JAMA Oncol 3:211–219
Warschkow R, SulzMC,Marti L, Tarantino I, Schmied BM, Cerny T, Guller U, 2016, Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer 16:554
Baran B, Ozupek NM, Tetik YN, Acar E, Bekcioglu O, Baskin Y, 2018, Difference between left-sided and right-sided colorectal cancer: a focused review of literature. Gastroenterol Res 11:264–273
Loree JM, Pereira AAL, Lam M, Willauer AN, Raghav K, Dasari A, Morris VK, Advani S, MenterDG, Eng C, Shaw K, Broaddus R, Routbort MJ, Liu Y, Morris JS, Luthra R, Meric-Bernstam F, Overman MJ, Maru D, Kopetz S, 2018, Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes. Clin Cancer Res 24:1062–1072
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1429
EP 1434
DI 10.1007/s12253-018-00572-2
PG 6
ER
PT J
AU Tarancon-Diez, M
Buttner, R
Friedrichs, N
AF Tarancon-Diez, Maria
Buttner, Reinhard
Friedrichs, Nicolaus
TI Enhanced Tumoral MLH1-Expression in MLH1-/PMS2-Deficient Colon Cancer Is Indicative of Sporadic Colon Cancer and Not HNPCC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; HNPCC; Lynch syndrome; MLH1; Mismatch repair enzymes
ID Colorectal cancer; HNPCC; Lynch syndrome; MLH1; Mismatch repair enzymes
AB Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is caused by germline mutations of mismatch-repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. MLH1-/PMS2-deficient colorectal carcinomas might be HNPCC-associated but also caused by MLH1-promoter methylation in sporadic colon carcinoma. This study analyzed semiquantitatively whether the MLH1 staining pattern might be indicative of sporadic or HNPCC-associated colorectal cancer. Using a semi-quantitative score ranging from 0 (negative) to 12 (maximum immunopositivity) we analyzed MLH1 expression patterns in 130 MLH1-/PMS2-deficient colorectal cancers. The collective consisted of 70 HNPCC-associated colorectal cancers and 60 sporadic colon cancers. In tumor cells of 70 HNPCC-associated colorectal cancers, 64 cases (91.43%) showed no MLH1 staining, 5 cases weak (7.14%) and 1 case (1.43%) stronger staining intensity. In contrast, in tumor cells of 60 sporadic colorectal cancers 45 cases (75.0%) showed no MLH1 staining, 10 cases weak (16.67%) and 5 cases (8.33%) stronger staining intensity to a varying extent. In immuno-positive cases, MLH1 showed a characteristic dot-like nuclear staining pattern in the tumor cells. We compared cases with absent to weak MLH1-staining (immuno-scores 0 to 2) to cases with elevated immuno-scores (3 to 12) detecting a statistically significant difference between HNPCC-associated and sporadic colon cancers (p value = 0.0031, Fisher’s exact test). Taken together, enhanced tumoral MLH1 expression in MLH1-/PMS2-deficient colorectal carcinomas seems to be indicative of sporadic origin. In contrast, HNPCC-associated colorectal cancer showed absent or very weak MLH1 immunopositivity. Therefore, this semiquantitative and easy to exert MLH1 immuno-score might help to identify sporadic MLH1-/PMS2-deficient colorectal cancer cases prior to time-consuming methylation analysis.
C1 [Tarancon-Diez, Maria] University of Cologne Medical School, Institute of Pathology, Kerpener Str. 62, 50937 Cologne, Germany.
[Buttner, Reinhard] University of Cologne Medical School, Institute of Pathology, Kerpener Str. 62, 50937 Cologne, Germany.
[Friedrichs, Nicolaus] University of Cologne Medical School, Institute of Pathology, Kerpener Str. 62, 50937 Cologne, Germany.
RP Friedrichs, N (reprint author), University of Cologne Medical School, Institute of Pathology, 50937 Cologne, Germany.
EM nicolaus.friedrichs@uk-koeln.de
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Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Muller-Koch Y, Keller G, Schackert HK, Kruger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Ruschoff J, Propping P, the German HNPCC Consortium, 2005, Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. Int J Cancer 116(5):692–702
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1435
EP 1439
DI 10.1007/s12253-018-00571-3
PG 5
ER
PT J
AU Aalijahan, H
Ghorbian, S
AF Aalijahan, Hamid
Ghorbian, Saeid
TI Clinical Application of Long Non-Coding RNA-UCA1 as a Candidate Gene in Progression of Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LncRNA-UCA1; Candidate gene; Esophageal Cancer; LncRNAs
ID LncRNA-UCA1; Candidate gene; Esophageal Cancer; LncRNAs
AB Esophageal cancer (EC) is known as one of the most prevalent gastrointestinal cancers, and results in the seventh highest number of cancer-relevant deaths. Long non-coding RNAs (lncRNAs) have substantial roles in several biological processes. LncRNA human urothelial carcinoma associated 1 (UCA1) is announced to be enhanced in multiple types of human cancers. This survey was carried out to identify the potential role of the lncRNA-UCA1 in the progression of EC. A case-control investigation was performed on 140 FFPE tissues of EC patients consisting of 70 cancerous tissues and 70 marginal tissues samples. To determine the lncRNA-UCA1 gene expression changes, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) method was utilized. In addition, the associations between the lncRNA-UCA1 gene expression and clinicopathological parameters were assessed. Our findings revealed that the lncRNA-UCA1 was notably up-regulated in EC tissues compared to adjacent normal tissues (P < 0.05). LncRNA-UCA1 expression was substantially correlated to alcohol drinking (P = 0.008) and socioeconomic status (P = 0.001), while shared no correlation with age, hot drinking status and stage (P > 0.05). Our data indicated that the lncRNA-UCA1 play an important role in the progression of EC and may be considered as a candidate gene in the pathogenesis of EC patients.
C1 [Aalijahan, Hamid] Islamic Azad University, Ahar Branch, Department of Molecular GeneticsAhar, Iran.
[Ghorbian, Saeid] Islamic Azad University, Ahar Branch, Department of Molecular GeneticsAhar, Iran.
RP Ghorbian, S (reprint author), Islamic Azad University, Ahar Branch, Department of Molecular Genetics, Ahar, Iran.
EM ghorbian20@yahoo.com;s_ghorbian@iau-ahar.ac.ir
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1441
EP 1446
DI 10.1007/s12253-019-00711-3
PG 6
ER
PT J
AU Kranitz, N
Szepesvary, Zs
Kocsis, K
Kullmann, T
AF Kranitz, Noemi
Szepesvary, Zsolt
Kocsis, Karoly
Kullmann, Tamas
TI Neuroendocrine Cancer of the Prostate
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroendocrine; Prostate cancer; Immunohistochemistry; Serum marker; Platinum
ID Neuroendocrine; Prostate cancer; Immunohistochemistry; Serum marker; Platinum
AB Neuroendocrine cancer of the prostate is considered to be a rare entity with bad prognosis and limited therapeutic options. We performed a prospective analysis of the patients treated in our hospital for prostate cancer between 1st January 2015 and 31rd December 2018. Neuroendocrine phenomena were tested by immunohistochemistry and laboratory chemistry on the request of the clinicians in the cases when a positive diagnosis was suspected. Clinical tableaux of high suspicion of neuroendocrine cancer included radiological progression of a metastatic disease without PSA rise, relatively extended metastatic disease associated to a low PSA, disease with non-pulmonary visceral metastases. 10 patients were diagnosed with neuroendocrine tumour out of 521 prostate cancers. Half of the patients had a survival over a year. 3 patients received 3 lines of efficacious palliative chemotherapy. 1 patient underwent prostatectomy after neoadjuvant chemotherapy for a localised disease. The incidence of neuroendocrine tumours among prostate cancer patients was higher than expected. Some of the patients had a relatively good outcome.
C1 [Kranitz, Noemi] Petz Aladar Hospital, Department of PathologyGyor, Hungary.
[Szepesvary, Zsolt] Petz Aladar Hospital, Department of UrologyGyor, Hungary.
[Kocsis, Karoly] Petz Aladar Hospital, Department of Oncoradiology, Vasvari Pal u. 2-4, 9024 Gyor, Hungary.
[Kullmann, Tamas] Petz Aladar Hospital, Department of Oncoradiology, Vasvari Pal u. 2-4, 9024 Gyor, Hungary.
RP Kullmann, T (reprint author), Petz Aladar Hospital, Department of Oncoradiology, 9024 Gyor, Hungary.
EM kullmanndoki@hotmail.com
CR Honn KV, Aref A, Chen YQ et al, 1996, Prostate cancer - old problems and new approaches., Part II. Diagnostic and prognostic markers, Pathology and Biological Aspects). Pathol Oncol Res 2: 191–211
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Kishore K, Rafeeq A, Chime C et al, 2018, Poorly differentiated small-cell-type neuroendocrine carcinoma of the prostate: a case report and literature review. Case Rep Oncol 11:676–681
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1447
EP 1450
DI 10.1007/s12253-019-00712-2
PG 4
ER
PT J
AU Li, Y
Yang, Sh
Yue, H
Yuan, D
Li, L
Zhao, J
Zhao, L
AF Li, Yan
Yang, Shouyan
Yue, Honggang
Yuan, Dandi
Li, Luxia
Zhao, Jinghong
Zhao, Lintao
TI Unraveling LGALS1 as a Potential Immune Checkpoint and a Predictor of the Response to Anti-PD1 Therapy in Clear Cell Renal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Immunotherapy; PD-L1; LGALS1; Galectin1; Clear cell renal carcinoma; Immune checkpoint
ID Immunotherapy; PD-L1; LGALS1; Galectin1; Clear cell renal carcinoma; Immune checkpoint
AB Immunotherapy base on immune checkpoint inhibitor had obtained significant progress in extending the survival of clear cell renal carcinoma (ccRCC) patients. In order to further improve the efficiency of immunotherapy, novel immune checkpoint inhibitors needed to be developed. Differentially expressed genes (DEGs) between healthy kidney tissues and ccRCC tissues had been found from GSE68417 by GEO2R online analysis tool. Correlation analysis and Kaplan–Meier survival analyses were based on UALCAN database. Analyses of the outcome of anti-PD1 treatment had been found from GSE67501 dataset. At first, 9 genes with higher expression were associated with shorter overall survival time. More importantly, higher expression of LGALS1 was correlated with a profitable outcome of anti-PD1 treatment and the combined the expression level of PD-L1 and LGALS1 together could more efficiently predict the outcome of anti-PD1 treatment than using PD-L1 alone. At last, the genes which correlated with LGALS1 expression in ccRCC patients were enriched in TNF alpha Signaling Pathway which is mainly correlated with T cell apoptosis and survival. Together, these suggest LGALS1 could be a potential immune checkpoint, which could promote tumor progression through affecting T cell survival.
C1 [Li, Yan] Army Medical University (Third Military Medical University), Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Department of Nephrology, 400037 Chongqing, China.
[Yang, Shouyan] Army Medical University (Third Military Medical University), 958th Hospital, Southwest Hospital, Department of Oncology, 400020 Chongqing, China.
[Yue, Honggang] Army Medical University (Third Military Medical University), 958th Hospital, Southwest Hospital, Department of Oncology, 400020 Chongqing, China.
[Yuan, Dandi] Army Medical University (Third Military Medical University), 958th Hospital, Southwest Hospital, Department of Oncology, 400020 Chongqing, China.
[Li, Luxia] Army Medical University (Third Military Medical University), 958th Hospital, Southwest Hospital, Department of Oncology, 400020 Chongqing, China.
[Zhao, Jinghong] Army Medical University (Third Military Medical University), Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Department of Nephrology, 400037 Chongqing, China.
[Zhao, Lintao] Army Medical University (Third Military Medical University), Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Department of Nephrology, 400037 Chongqing, China.
RP Zhao, J (reprint author), Army Medical University (Third Military Medical University), Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Department of Nephrology, 400037 Chongqing, China.
EM zhaojh@tmmu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1451
EP 1458
DI 10.1007/s12253-019-00710-4
PG 8
ER
PT J
AU Liu, ZQ
Lu, MY
Liu, B
AF Liu, Zhi-Qin
Lu, Mei-Yin
Liu, Bin
TI Polymorphisms in XPC Gene and Risk of Uterine Leiomyoma in Reproductive Women
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Uterine leiomyoma; XPC; Polymorphism; Genetic susceptibility
ID Uterine leiomyoma; XPC; Polymorphism; Genetic susceptibility
AB XPC gene belongs to DNA repair pathway, which is involved in the development of uterine leiomyoma. However, its relationships with leiomyoma risk were never reported. We here hypothesized that XPC gene was associated with the risk of uterine leiomyoma. In this case–control study with a total of 391 leiomyoma cases and 493 tumor-free controls in a reproductive women population in South China, two missense polymorphisms rs2228001 A > C (Lys939Gln) and rs2228000 C > T (Ala499Val) were genotyped by quantitative polymerase chain reaction (qPCR). Then, the associations between these two polymorphisms and leiomyoma risk were investigated. It was revealed that the rs2228000 CT/TT variant genotypes had a decreased leiomyoma risk (adjusted odds ratio = 0.73, 95% confidence interval = 0.54–0.94) compared with rs2228000 CC genotype. Further stratified analysis also revealed that the protective effect of rs2228000 CT/TT on the risk of uterine leiomyoma was more evident among subjects who were younger than 35 years old compared with those with larger tumors (diameter of tumor >5 cm), and those with fewer number of myomas (only one). However, no significant association was observed for leiomyoma risk for rs2228001 A > C. This study indicated that genetic variations in XPC gene are associated with leiomyoma susceptibility in a reproductive women population. It warrants further confirmation in larger prospective studies with different populations.
C1 [Liu, Zhi-Qin] Jinan University, Baoan Maternal and Child Health Hospital, Department of Obstetrics and GynecologyShenzhen, Guangdong, China.
[Lu, Mei-Yin] Jinan University, Baoan Maternal and Child Health Hospital, Department of Biobank, 518102 Shenzhen, Guangdong, China.
[Liu, Bin] Jinan University, Baoan Maternal and Child Health Hospital, Department of Biobank, 518102 Shenzhen, Guangdong, China.
RP Liu, B (reprint author), Jinan University, Baoan Maternal and Child Health Hospital, Department of Biobank, 518102 Shenzhen, China.
EM gz12liubin@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1459
EP 1464
DI 10.1007/s12253-019-00720-2
PG 6
ER
PT J
AU Respondek, M
Beberok, A
Rzepka, Z
Rok, J
Wrzesniok, D
AF Respondek, Michalina
Beberok, Artur
Rzepka, Zuzanna
Rok, Jakub
Wrzesniok, Dorota
TI Mcl-1 Inhibitor Induces Cells Death in BRAF-Mutant Amelanotic Melanoma Trough GSH Depletion, DNA Damage and Cell Cycle Changes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Amelanotic melanoma; Apoptosis; BH3 mimetics; MIM1; Dacarbazine; image cytometry
ID Amelanotic melanoma; Apoptosis; BH3 mimetics; MIM1; Dacarbazine; image cytometry
AB Mcl-1 is a potent antiapoptotic protein and amplifies frequently in many human cancer. Currently, it is considered that the extensively expressed of Mcl-1 protein in melanoma cells is associated with rapid tumor progression, poor prognosis and low chemosensitivity. Therefore, the antiapoptotic protein Mcl-1 could be considered as a potential target for malignant melanoma treatment. The aim of this study was to assess the effect of MIM1 a specific low molecular Mcl-1 protein inhibitor and mixture of MIM1 and dacarbazine on the viability, cell cycle progression and apoptosis induction in amelanotic C32 melanoma cells. The cytotoxic activity of MIM1 towards C32 melanoma cells was examined by the WST-1 test. The Mcl-1 protein level as a drug target in amelanotic melanoma cells was defined by Western blot analysis. Cell cycle progression, DNA fragmentation as well as GSH depletion were determined by fluorescence image cytometer NucleoCounter NC-3000. The obtained results demonstrate that the specific Mcl-1 protein inhibitor - MIM1 decreases cell viability and induce apoptosis (S-phase arrest, DNA fragmentation and redox imbalance) in amelanotic melanoma cells and intensify the proapoptotic properties of DTIC, as a result of interactions with Mcl-1 protein. Taken together, the presented data suggest that Mcl-1 protein is a an important target in malignant melanoma treatment and provide for the first time convincing evidence that MIM1, which inhibits Mcl-1 antiapoptotic protein is able to induce apoptosis and sensitize melanoma cells to alkylating agent.
C1 [Respondek, Michalina] Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Jagiellonska 4, 41-200 Sosnowiec, Poland.
[Beberok, Artur] Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Jagiellonska 4, 41-200 Sosnowiec, Poland.
[Rzepka, Zuzanna] Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Jagiellonska 4, 41-200 Sosnowiec, Poland.
[Rok, Jakub] Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Jagiellonska 4, 41-200 Sosnowiec, Poland.
[Wrzesniok, Dorota] Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Jagiellonska 4, 41-200 Sosnowiec, Poland.
RP Respondek, M (reprint author), Medical University of Silesia, Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, 41-200 Sosnowiec, Poland.
EM mrespondek@sum.edu.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1465
EP 1474
DI 10.1007/s12253-019-00715-z
PG 10
ER
PT J
AU Shao, Y
Tao, X
Lu, R
Zhang, H
Ge, J
Xiao, B
Ye, G
Guo, J
AF Shao, Yongfu
Tao, Xueping
Lu, Rongdan
Zhang, Haiqiang
Ge, Jiaxin
Xiao, Bingxiu
Ye, Guoliang
Guo, Junming
TI Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CircRNA; Hsa_circ_0065149; Exosomes; Gastric juice; Biomarker
ID CircRNA; Hsa_circ_0065149; Exosomes; Gastric juice; Biomarker
AB Circular RNAs (circRNAs) are an endogenous RNAs with a covalently closed cyclic structure. They have emerged recently as key regulators in the development and progression of human cancers. However, the clinical values of most circRNAs in gastric cancer (GC) are unknown. Hsa_circ_0065149, one of the dysregulated circRNAs in gastric carcinogenesis detected by circRNA microarray, was chose as a targeted circRNA in this study. We firstly enlarged sample size and identified the level changes of hsa_circ_0065149 among four stages of gastric tumorigenesis from healthy gastric mucosa, gastritis, intestinal metaplasia to GC. Then, the potential relationship between hsa_circ_0065149 expression levels and GC patients’ clinicopathological factors was investigated. Moreover, the clinical significance of hsa_circ_0065149 in plasma exosomes and gastric juice were explored. Receiver operating characteristic (ROC) curve and Kaplan-Meier survival curve were constructed to evaluate diagnostic and prognostic values. Finally, bioinformatics analysis was performed to excavate the potential functions of hsa_circ_0065149. Hsa_circ_0065149 expression was only significantly down-regulated in gastric cancer, not changed among healthy gastric mucosa and gastritis intestinal metaplasia. Low hsa_circ_0065149 expression levels in GC tissues were significantly associated with tumor diameter (P = 0.034) and perineural invasion (P = 0.037). GC patients with low hsa_circ_0065149 levels had a much longer overall survival than those in high group (P = 0.020). More important, hsa_circ_0065149 levels were significantly decreased in plasma exosomes of early GC patients. As a screening biomarker for early GC, hsa_circ_0065149 in plasma exosomes has higher sensitivity and specificity than traditional clinical biomarkers. Bioinformatics analysis suggest that the abnormal expression of hsa_circ_0065149 may play an important role during gastric carcinogenesis. Those results indicate that hsa_circ_0065149 in exosomes is an indicator for early GC screening and prognosis prediction.
C1 [Shao, Yongfu] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Tao, Xueping] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Lu, Rongdan] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Zhang, Haiqiang] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Ge, Jiaxin] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Xiao, Bingxiu] Ningbo University School of Medicine, Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, 315211 Ningbo, China.
[Ye, Guoliang] The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
[Guo, Junming] Ningbo University School of Medicine, Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, 315211 Ningbo, China.
RP Ye, G (reprint author), The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, 315020 Ningbo, China.
EM ndfyygl@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1475
EP 1482
DI 10.1007/s12253-019-00716-y
PG 8
ER
PT J
AU Picasso, R
Tagliafico, A
Calabrese, M
Martinoli, C
Pistoia, F
Rossi, A
Zaottini, F
Derchi, L
AF Picasso, Riccardo
Tagliafico, Alberto
Calabrese, Massimo
Martinoli, Carlo
Pistoia, Federico
Rossi, Anna
Zaottini, Federico
Derchi, Lorenzo
TI Primary and Secondary Breast Lymphoma: Focus on Epidemiology and Imaging Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast; Lymphoma; Epidemiology; Imaging
ID Breast; Lymphoma; Epidemiology; Imaging
AB Aim of this study was to select all the cases of Primary (PBL) and Secondary (SBL) Breast Lymphoma from our breast unit since 01/01/2000, to obtain up-to-date data on the prevalence of this rare pathology and to analyze imaging features, with a special focus on CT. All pathological reports of breast biopsies performed from 01/01/2000 to 01/01/2019 were at first screened. Among them, we performed two different researches, looking for key words suggesting either a diagnosis of lymphoma or any other malignant disease. Using the Wiseman criteria, we identify PBL and SBL. All imaging features of PBL and SBL were analyzed. Prevalence of lymphoma amongst suspicious breast masses and amongst all breast malignancies were calculated. Out of 42,505 histopathology reports from mammary nodule biopsies, we found 19,354 malignancies. We were able to identify 11 patients affected by PBL (0,03% of suspicious breast lesions, 0.06% of breast malignancies), and 23 cases of SBL (0,05% of suspicious breast lesions, 0,12%of breast malignancies).Most common isotype in PBL was DLBC lymphoma, whereas in SBL that resulted Follicular lymphoma. In PBL group, we were able to retrieve images 7 CT or CT-PET study performed at diagnosis 7 US, 1 mammography and 1 MR. In SBL group, we analyzed 14 CT/CT-PET examinations, 11 US studies and 3 mammography. PBL and SBL are rarer than considered until now. There is no definite imaging characteristic able to distinguish between these two pathologies and among them and breast cancer.
C1 [Picasso, Riccardo] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
[Tagliafico, Alberto] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
[Calabrese, Massimo] Ospedale Policlinico San MartinoGenova, Italy.
[Martinoli, Carlo] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
[Pistoia, Federico] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
[Rossi, Anna] Ospedale Policlinico San MartinoGenova, Italy.
[Zaottini, Federico] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
[Derchi, Lorenzo] University of Genova, Department of Health Sciences (DISSAL), Radiology Section, Via Pastore, 1-16132 Genova, Italy.
RP Picasso, R (reprint author), University of Genova, Department of Health Sciences (DISSAL), Radiology Section, 1-16132 Genova, Italy.
EM Riccardo.picasso@gmail.com
CR Sabate JM, Gomez A, Torrubia S et al, 2002, Lymphoma of the breast: clinical and radiologic features with pathologic correlation in 28 patients. Breast J 8:294–304
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Giardini R, Piccolo C, Rilke F. Primary non-Hodgkin's lymphomas of the female breast. Cancer 1992;69:725±35, 735
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Surov A, Holzhausen HJ, Wienke A, Schmidt J, Thomssen C, Arnold D, Ruschke K, Spielmann RP, 2012, Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features. Br J Radiol 85:e195–e205
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Harvey JA,MahoneyMC, NewellMS, Bailey L, Barke LD,D’Orsi C, Hayes MK, Jokich PM, Lee SJ, Lehman CD, Mainiero MB, Mankoff DA, Patel SB, Reynolds HE, Sutherland ML, Haffty BG, 2013, ACR appropriateness criteria palpable breast masses. J Am Coll Radiol 10:742–749
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1483
EP 1488
DI 10.1007/s12253-019-00730-0
PG 6
ER
PT J
AU Malik, UU
Siddiqui, AI
Ilyas, A
Hashim, Z
Staunton, L
Kwasnik, A
Pennington, RS
Shamshad, Z
AF Malik, Urooj Uzma
Siddiqui, Ather Imtiaz
Ilyas, Amber
Hashim, Zehra
Staunton, Lisa
Kwasnik, Anna
Pennington, R Stephen
Shamshad, Zarina
TI Identification of Differentially Expressed Proteins from Smokeless Tobacco Addicted Patients Suffering from Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Tissue proteomics; Differential expression; Biomarker; Smokeless tobacco
ID Oral squamous cell carcinoma; Tissue proteomics; Differential expression; Biomarker; Smokeless tobacco
AB Oral squamous cell carcinoma (OSCC) is the eight most common malignancy worldwide with an incidence rate of 40%in southeast Asia. Lack of effective diagnostic tools at early stage and disease recurrence despite extensive treatments are main reasons for high mortality and low survival rates. The aim of current study was to identify differentially expressed proteins to explore potential candidate biomarkers having diagnostic significance. We performed comparative proteomic analysis of paired protein samples (cancerous buccal mucosa and adjacent normal tissue) from OSCC patients using a combination of two dimensional gel electrophoresis and Mass spectrometric analysis. On the basis of spot intensity, seventeen proteins were found to be consistently differentially expressed among most of the samples which were identified through mass spectrometry. For validation of identified proteins, expression level of stratifin was determined using immuno-histochemistry and Western blot analysis. All identified proteins were analyzed by STRING to explore their interaction. Among uniquely identified proteins in this study, at least two candidate markers (Ig Kappa chain C region and Isoform 2 of fructose bisphosphate aldolase A) were found to be novel with respect to OSCC which can be explored further. Results presented in current study are likely to contribute in understanding the involvement of these molecules in carcinogenesis apart from their plausible role as diagnostic/prognostic markers.
C1 [Malik, Urooj Uzma] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Siddiqui, Ather Imtiaz] Jinnah Postgraduate MedicalKarachi, Pakistan.
[Ilyas, Amber] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Hashim, Zehra] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Staunton, Lisa] University College Dublin, School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical ResearchDublin, Ireland.
[Kwasnik, Anna] University College Dublin, School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical ResearchDublin, Ireland.
[Pennington, R Stephen] University College Dublin, School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical ResearchDublin, Ireland.
[Shamshad, Zarina] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
RP Shamshad, Z (reprint author), University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
EM szarina@uok.edu.pk
CR Ferlay J, Soerjomataram R, Dikshit R, Eser S, Mathers C, RebeloM et al, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386
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Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, Cadenas C,Marchan R, Stewart JD, Solbach C, Holmberg L, Edlund K, Kultima HG, Rody A, Berglund A, LambeM, Isaksson A, Botling J, Karn T,Muller V, Gerhold-Ay A, Cotarelo C, Sebastian M, Kronenwett R, Bojar H, Lehr HA, Sahin U, Koelbl H, Gehrmann M, Micke P, Rahnenfuhrer J, Hengstler JG, 2012, A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors. Clin Cancer Res 18:2695–2703
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1489
EP 1497
DI 10.1007/s12253-019-00724-y
PG 9
ER
PT J
AU Tokes, T
Tokes, AM
Szentmartoni, Gy
Kiszner, G
Muhl, D
Molnar, B
Kulka, J
Krenacs, T
Dank, M
AF Tokes, Timea
Tokes, Anna-Maria
Szentmartoni, Gyongyver
Kiszner, Gergo
Muhl, Dorottya
Molnar, Akos Bela
Kulka, Janina
Krenacs, Tibor
Dank, Magdolna
TI Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Primary systemic therapy; Cell cycle; Ki67; MCM; CyclinA; PHH3
ID Breast cancer; Primary systemic therapy; Cell cycle; Ki67; MCM; CyclinA; PHH3
AB We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki- 67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (p < 0.01 and p < 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (p = 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.
C1 [Tokes, Timea] Semmelweis University, Department of Oncology, Tomo utca 25-29, 4th floor, H-1083 Budapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Szentmartoni, Gyongyver] Semmelweis University, Department of Oncology, Tomo utca 25-29, 4th floor, H-1083 Budapest, Hungary.
[Kiszner, Gergo] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Muhl, Dorottya] Semmelweis University, Department of Oncology, Tomo utca 25-29, 4th floor, H-1083 Budapest, Hungary.
[Molnar, Akos Bela] Semmelweis University, 1st Department of Surgery, Ulloi ut 78/A, H-1083 Budapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of Oncology, Tomo utca 25-29, 4th floor, H-1083 Budapest, Hungary.
RP Tokes, T (reprint author), Semmelweis University, Department of Oncology, H-1083 Budapest, Hungary.
EM timi.tokes@gmail.com;tokes.timea@med.semmelweis-univ.hu
CR Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ, Gallen S, 2007, Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol 18:1133–1144
Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B et al, 2013, Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol 24:2206–2223
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1499
EP 1510
DI 10.1007/s12253-019-00726-w
PG 12
ER
PT J
AU Wangmo, Ch
Charoen, N
Jantharapattana, K
Dechaphunkul, A
Thongsuksai, P
AF Wangmo, Chimi
Charoen, Nattinee
Jantharapattana, Kitti
Dechaphunkul, Arunee
Thongsuksai, Paramee
TI Epithelial–Mesenchymal Transition Predicts Survival in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epithelial–mesenchymal transition; E-cadherin; Vimentin; p16; Oral squamous cell carcinoma; Prognosis; Immunohistochemistry
ID Epithelial–mesenchymal transition; E-cadherin; Vimentin; p16; Oral squamous cell carcinoma; Prognosis; Immunohistochemistry
AB Synergistic loss of E-cadherin and acquisition of vimentin are characteristic feature of epithelial–mesenchymal transition (EMT) which confers an invasive phenotype of epithelial cancer cells. The aim of the study was to evaluate the prognostic significance of E-cadherin and vimentin expression individually and in combination as a measure of epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Expression of E-cadherin and vimentin through immunohistochemical analysis was examined in 200 patients with surgically resected OSCC. Combined E-cadherin and vimentin expression was evaluated to determine the EMT status. Kaplan–Meier curves and log-rank test were used to compare differences in survival. Cox regression analysis was performed to identify independent prognostic factors. E-cadherin expression was negative in 28 (14%) tumors, and vimentin expression was positive in 87 (43.5%) tumors. Moreover, 99 (49.5%), 87 (43.5%), and 14 (7.5%) tumors exhibited no, partial, and complete EMT, respectively. Both individual protein expression were significant prognostic factors [Negative E-cadherin, hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.04–2.93; positive vimentin, HR = 1.64, 95% CI = 1.12–2.41]. For EMT status, the HR increased with EMT progression [partial EMT, HR = 1.64, 95% CI = 1.09–2.49; complete EMT, HR = 2.88, 95% CI = 1.44–5.79], of which, the complete EMT had higher HR than was individual protein expression. Combined E-cadherin and vimentin expression as a measure of EMT showed a superior prognostic significance compared with individual protein expression.
C1 [Wangmo, Chimi] Prince of Songkla University, Faculty of Medicine, Department of Pathology, 90110 Hat Yai, Songkhla, Thailand.
[Charoen, Nattinee] Prince of Songkla University, Faculty of Medicine, Department of Pathology, 90110 Hat Yai, Songkhla, Thailand.
[Jantharapattana, Kitti] Prince of Songkla University, Faculty of Medicine, Department of Otolaryngology Head and Neck Surgery, 90110 Hat Yai, Songkhla, Thailand.
[Dechaphunkul, Arunee] Prince of Songkla University, Faculty of Medicine, Division of Medical Oncology, Department of Internal Medicine, 90110 Hat Yai, Songkhla, Thailand.
[Thongsuksai, Paramee] Prince of Songkla University, Faculty of Medicine, Department of Pathology, 90110 Hat Yai, Songkhla, Thailand.
RP Thongsuksai, P (reprint author), Prince of Songkla University, Faculty of Medicine, Department of Pathology, 90110 Hat Yai, Thailand.
EM tparamee@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1511
EP 1518
DI 10.1007/s12253-019-00731-z
PG 8
ER
PT J
AU Marangon, GC
de Bitencorte, TJ
Michita, TR
Lunge, RV
dos Santos, CD
Alvares-da-Silva, RM
Simon, D
AF Marangon, Guerra Camila
de Bitencorte, Teixeira Joice
Michita, Tomoya Rafael
Lunge, Ricardo Vagner
dos Santos, Cruz Deivid
Alvares-da-Silva, Reis Mario
Simon, Daniel
TI Association between MICA rs2596542 Polymorphism with the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HCV; Hepatocellular carcinoma; Liver cirrhosis; MICA gene; rs2596542; HCC
ID HCV; Hepatocellular carcinoma; Liver cirrhosis; MICA gene; rs2596542; HCC
AB In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06–3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00–3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.
C1 [Marangon, Guerra Camila] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e MolecularCanoas, RS, Brazil.
[de Bitencorte, Teixeira Joice] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e MolecularCanoas, RS, Brazil.
[Michita, Tomoya Rafael] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e MolecularCanoas, RS, Brazil.
[Lunge, Ricardo Vagner] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e MolecularCanoas, RS, Brazil.
[dos Santos, Cruz Deivid] Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clinicas de Porto Alegre, Servico de Gastroenterologia, Departamento de Medicina InternaPorto Alegre, RS, Brazil.
[Alvares-da-Silva, Reis Mario] Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clinicas de Porto Alegre, Servico de Gastroenterologia, Departamento de Medicina InternaPorto Alegre, RS, Brazil.
[Simon, Daniel] Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e MolecularCanoas, RS, Brazil.
RP Simon, D (reprint author), Universidade Luterana do Brasil, Programa de Pos Graduacao em Diagnostico Genetico e Molecular, Canoas, Brazil.
EM daniel.simon@ulbra.br
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1519
EP 1525
DI 10.1007/s12253-019-00738-6
PG 7
ER
PT J
AU Gregova, M
Hojny, J
Nemejcova, K
Bartu, M
Mara, M
Boudova, B
Laco, J
Krbal, L
Ticha, I
Dundr, P
AF Gregova, Maria
Hojny, Jan
Nemejcova, Kristyna
Bartu, Michaela
Mara, Michal
Boudova, Barbora
Laco, Jan
Krbal, Lukas
Ticha, Ivana
Dundr, Pavel
TI Leiomyoma with Bizarre Nuclei: a Study of 108 Cases Focusing on Clinicopathological Features, Morphology, and Fumarate Hydratase Alterations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Leiomyoma with bizarre nuclei; Usual leiomyoma; Leiomyosarcoma; Fumarate hydratase
ID Leiomyoma with bizarre nuclei; Usual leiomyoma; Leiomyosarcoma; Fumarate hydratase
AB Leiomyoma with bizarre nuclei (LBN) is an uncommon variant of uterine smooth muscle neoplasm. Involvement of fumarate hydratase (FH) has been suggested in the pathogenesis of a subset of LBN. The goal of our study is to assess the clinicopathological, morphological, immunohistochemical and molecular findings focusing on FH in LBNs (n = 108) and compare it with the findings in usual leiomyomas (UL; n = 50) and leiomyosarcomas (LMS; n = 42). Immunohistochemically, loss of FH expression was found in 67/108 of LBN, 1/50 of UL and in no LMS. Class 4/5 FH mutations were detected in 15/53 LBN with sufficient DNA quality for molecular analysis. Pathogenic variants of the FH gene were detected in neither UL nor LMS. Local recurrence after surgery was present in 18/92 of LBN patients, 7 of which were histologically verified and 2 of which were found to be LBN. Our results confirmed that LBN behave in a benign fashion, although they may relapse. FH gene mutations were a common finding only in LBN, but not in UL and LMS. Immunohistochemistry with an antibody against FH seems to have a good sensitivity (87%) and moderate specificity (58%) with regard to predicting FH gene mutations and could be used as a screening method in tumors with features suggestive of FH alterations to identify patients who are at risk for the FH aberrations.
C1 [Gregova, Maria] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Hojny, Jan] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Nemejcova, Kristyna] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Bartu, Michaela] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Mara, Michal] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
[Boudova, Barbora] Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Obstetrics and GynecologyPrague, Czech Republic.
[Laco, Jan] Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of PathologyPrague, Czech Republic.
[Krbal, Lukas] Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of PathologyPrague, Czech Republic.
[Ticha, Ivana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 12800 Prague, Czech Republic.
EM pavel.dundr@vfn.cz
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1527
EP 1537
DI 10.1007/s12253-019-00739-5
PG 11
ER
PT J
AU Peters, AMM
Meijer, C
Fehrmann, SNR
Walenkamp, MEA
Kema, PI
de Vries, GEE
Hollema, H
Oosting, FS
AF Peters, A M Marloes
Meijer, Coby
Fehrmann, S N Rudolf
Walenkamp, M E Annemiek
Kema, P Ido
de Vries, G E Elisabeth
Hollema, Harry
Oosting, F Sjoukje
TI Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serotonin receptor 1B; Serotonin receptor 2B; Dopamine receptor D2; Dopamine receptor D1; Neovascularization; Neoplasms
ID Serotonin receptor 1B; Serotonin receptor 2B; Dopamine receptor D2; Dopamine receptor D1; Neovascularization; Neoplasms
AB In preclinical studies serotonin stimulates and dopamine inhibits tumour growth and angiogenesis. Information regarding serotonin and dopamine receptor (5-HTR and DRD) expression in human cancers is limited. Therefore, we screened a large tumour set for receptor mRNA overexpression using functional genomic mRNA (FGmRNA) profiling, and we analysed protein expression and location of 5-HTR1B, 5-HTR2B, DRD1, and DRD2 with immunohistochemistry in different tumour types. With FGmRNA profiling 11,756 samples representing 43 tumour types were compared to 3,520 normal tissue samples to analyse receptor overexpression. 5-HTR2B overexpression was present in many tumour types, most frequently in uveal melanomas (56%). Receptor overexpression in rare cancers included 5-HTR1B in nasopharyngeal carcinoma (17%), DRD1 in ependymoma (30%) and synovial sarcoma (21%), and DRD2 in astrocytoma (13%). Immunohistochemistry demonstrated high 5-HTR2B protein expression on melanoma and gastro-intestinal stromal tumour cells and endothelial cells of colon, ovarian, breast, renal and pancreatic tumours. 5-HTR1B expression was predominantly low. High DRD2 protein expression on tumour cells was observed in 48% of pheochromocytomas, and DRD1 expression ranged from 14% in melanoma to 57% in renal cell carcinoma. In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target.
C1 [Peters, A M Marloes] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
[Meijer, Coby] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
[Fehrmann, S N Rudolf] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
[Walenkamp, M E Annemiek] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
[Kema, P Ido] University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, 9700 Groningen, RB, The Netherlands.
[de Vries, G E Elisabeth] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
[Hollema, Harry] University of Groningen, University Medical Center Groningen, Department of Pathology, 9700 Groningen, RB, The Netherlands.
[Oosting, F Sjoukje] University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9700 Groningen, RB, The Netherlands.
RP Oosting, FS (reprint author), University of Groningen, University Medical Center Groningen, Department of Medical Oncology, 9700 Groningen, The Netherlands.
EM s.oosting@umcg.nl
CR Beaulieu JM, Gainetdinov RR, 2011, The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182– 217
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1539
EP 1547
DI 10.1007/s12253-019-00734-w
PG 9
ER
PT J
AU Sun, QX
Wang, RR
Liu, N
Liu, Ch
AF Sun, Qing-Xiu
Wang, Rong-Rong
Liu, Na
Liu, Chao
TI Dysregulation of miR-204-3p Driven by the Viability and Motility of Retinoblastoma via Wnt/β-catenin Pathway In Vitro and In Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Long non-coding RNA-BANCR; microRNA-204-3p; Retinoblastoma; WNT signaling pathway; Viability; Motility
ID Long non-coding RNA-BANCR; microRNA-204-3p; Retinoblastoma; WNT signaling pathway; Viability; Motility
AB Retinoblastoma (RB) is a malignant intraocular tumor that frequently occurs in infants and toddlers. Although the most of RB patients in the developed countries could survival from this cancer, the patients in undeveloped areas are still suffering. The human retinal pigment epithelial cell line ARPE-19 and human retinoblastoma (RB) cell lines HXO-RB44, Y79, and WERI-Rb1 were cultured. The mRNA levels of BANCR and miR-204-3p in these cell lines were measured by qRT-PCR. After transfection with sh-BANCR or treatment with miR-204-3p inhibitor in Y79 cells, the cell proliferation rate, growth, invasion, migration, apoptosis and Wnt/β-catenin signaling pathway activity were measured. The regular Y79 and Y79 cells stably expressed sh- BANCR were injected subcutaneously into nude mice, respectively. The volumes and pathohistological futures of tumors were compared. The biochemical features similar to the cell culture were detected and compered. The mRNA measurements showed that BANCR negatively modulate miR-204-3p expression via directly integration with it. Besides, miR-204-3p and Wnt/β- catenin signalling pathway were found to participate in the oncogenic effects of BANCR on RB cell line by Hoechst staining, cell Counting Kit-8 (CCK-8) assay, wound healing assay, Transwell assay, and Western blot analysis in vitro. In addition, an in vivo tumorigenesis experiment in nude mice injected with Y79 cells stably expressed sh-BANCR conformed in the effects of BANCR on RB. Taken together, the knockdown of BANCR inhibited cell proliferation, apoptosis, invasion, and migration in RB via targeting miR-204-3p, the mechanism may involve inhibiting Wnt/β-catenin signaling pathway.
C1 [Sun, Qing-Xiu] The Second Clinical Medical College of Qingdao University, Department of OphthalmologyQingdao, China.
[Wang, Rong-Rong] The Second Clinical Medical College of Qingdao University, Department of OphthalmologyQingdao, China.
[Liu, Na] The Second Clinical Medical College of Qingdao University, Department of OphthalmologyQingdao, China.
[Liu, Chao] The Second Clinical Medical College of Qingdao University, Department of OphthalmologyQingdao, China.
RP Liu, Ch (reprint author), The Second Clinical Medical College of Qingdao University, Department of Ophthalmology, Qingdao, China.
EM cha0liu@yandex.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1549
EP 1558
DI 10.1007/s12253-019-00722-0
PG 10
ER
PT J
AU Liu, L
Zhang, JW
Zhu, NSh
Zhu, Y
Guo, B
Yang, XH
AF Liu, Liu
Zhang, Jin-Wei
Zhu, Ni-Sha
Zhu, Yun
Guo, Bing
Yang, Xi-Hu
TI Clear Cell Odontogenic Carcinoma: a Clinicopathological and Immunocytochemical Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Head and neck; Clear cell odontogenic carcinoma; Oral cancer; Prognosis
ID Head and neck; Clear cell odontogenic carcinoma; Oral cancer; Prognosis
AB Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor associated with aggressive clinical behavior, metastasis and low survival. To date, only 67 cases have been described in the English language literature, and an understanding of the behavior of CCOC has been based on limited case reports. The aim of the research was to further reveal the features of CCOC. We report 5 new cases of CCOC, with a mean age of 52.4 years. The clinical and histopathologic data of the disease obtained from earlier literature (95 cases) and the 5 new cases were analyzed. Data were extracted, including demographics, histopathologic findings, clinical presentation, primary treatment and outcomes. Immunohistochemical results revealed that the cancer is positive for AE1/AE3, EMA and CK19, negative for smooth muscle actin SMA, Vim and S-100. EWSR1 translocation was also observed in the new cases, which may help in the diagnosis of CCOC. Metastases of CCOC were rare, but the local recurrence rate of CCOC rose to 42%. The best treatment for patients with CCOC is wide local excision combined with regional lymph node dissection.
C1 [Liu, Liu] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial-Head & Neck Oncology, 200011 Shanghai, China.
[Zhang, Jin-Wei] Third Central Hospital, Branch of Tianjin, Department of Stomatology, 300000 Tianjin, China.
[Zhu, Ni-Sha] Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial Surgery, 210000 Nanjing, Jiangsu, China.
[Zhu, Yun] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial-Head & Neck Oncology, 200011 Shanghai, China.
[Guo, Bing] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial-Head & Neck Oncology, 200011 Shanghai, China.
[Yang, Xi-Hu] Affiliated Hospital of Jiangsu University, Department of Oral and Maxillofacial Surgery, 212000 Zhenjiang, Jiangsu, China.
RP Guo, B (reprint author), Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial-Head & Neck Oncology, 200011 Shanghai, China.
EM doctorguo117@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1559
EP 1564
DI 10.1007/s12253-019-00741-x
PG 6
ER
PT J
AU Sirak, I
Pohankova, D
Ferko, A
Hovorkova, E
Rozkos, T
Vosmik, M
Hodek, M
Paluska, P
Buka, D
Grepl, J
Petera, J
AF Sirak, Igor
Pohankova, Denisa
Ferko, Alexander
Hovorkova, Eva
Rozkos, Tomas
Vosmik, Milan
Hodek, Miroslav
Paluska, Petr
Buka, David
Grepl, Jakub
Petera, Jiri
TI The Time Between Chemoradiation and Surgery for Rectal Carcinoma Negatively Influences Mesorectal Excision Quality
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rectal carcinoma; Neoadjuvant chemoradiation; Mesorectal excision
ID Rectal carcinoma; Neoadjuvant chemoradiation; Mesorectal excision
AB Total mesorectal excision quality (TMEq) is a prognostic factor associated with local recurrence in rectal adenocarcinoma. Neoadjuvant chemoradiotherapy (NCRT) reduces the risk of tumor recurrence, but may compromise TMEq. The time between NCRT and surgery (TTS) and how it influences TMEq and tumor control were evaluated. In prospective registry, 236 patients after NCRT and TME were analyzed. NCRT involved radiotherapy with 45 Gy to the pelvis, plus tumor boost dose 5.4 Gy with concurrent 5-fluorouracil infusion. NCRT was followed by TME after 9 weeks on average (median 9.4 ± SD 2.5). TMEq was parametrically analyzed by standard three-grade system. With median follow-up of 47.5 months, 3-year overall survival (OS) was 83.8%, disease-free survival (DFS) was 77.7%, and 6.4% was the rate of local recurrence (LR). TTS was not associated with OS, DFS, or LR. TMEq was found to be associated with LR in univariate analysis, but not in multivariate, where pathological tumor stage and resection margins remained dominant predictors. TMEq was negatively influenced by inferior location of the tumor, longer TTS, higher tumor and nodal stage, presence of tumor perforation, perineural invasion, and close/positive resection margins. Nonetheless, TTS remained a strong predictor of TMEq in multivariate analyses. TTS was proven to be an independent predictor of TMEq. With longer TTS, fewer complete TME with intact mesorectal plane were observed. However, TTS was not associated with survival deterioration or tumor recurrence. These were negatively influenced by other factors interfering with TMEq, especially by pathological tumor stage and resection margins.
C1 [Sirak, Igor] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Pohankova, Denisa] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Ferko, Alexander] Comenius University Bratislava, Jessenius Faculty in Martin, University Hospital Martin, Department of Surgery and Transplant CentreBratislava, Slovakia.
[Hovorkova, Eva] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Rozkos, Tomas] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, The Fingerland Department of PathologyHradec Kralove, Czech Republic.
[Vosmik, Milan] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Hodek, Miroslav] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Paluska, Petr] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Buka, David] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Grepl, Jakub] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
[Petera, Jiri] Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
RP Vosmik, M (reprint author), Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Department of Oncology and Radiotherapy, 500 05 Hradec Kralove, Czech Republic.
EM milan.vosmik@fnhk.cz
CR Parfitt JR, Driman DK, 2007, The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol 60(8):849–855
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1565
EP 1572
DI 10.1007/s12253-019-00742-w
PG 8
ER
PT J
AU Raju K, L
Haragannavar, CV
Patil, Sh
Rao, SR
Nagaraj, T
Augustine, D
Venkatesiah, SS
Nambiar, Sh
AF Raju K, Lizbeth
Haragannavar, C Vanishri
Patil, Shankargouda
Rao, S Roopa
Nagaraj, Tejavathi
Augustine, Dominic
Venkatesiah, S Sowmya
Nambiar, Shwetha
TI Expression of hTERT in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma – an Immunohistochemical Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarkers; Carcinogenesis; Immunohistochemistry; Oral submucous fibrosis; Squamous cell carcinoma; Telomerase
ID Biomarkers; Carcinogenesis; Immunohistochemistry; Oral submucous fibrosis; Squamous cell carcinoma; Telomerase
AB Human telomerase reverse transcriptase enzyme, the catalytic subunit of telomerase are seen to be frequently reactivated in cancers including Oral squamous cell carcinoma (OSCC). Increased hTERT expression have been seen in potentially malignant conditions including Oral submucous fibrosis (OSMF). The aim of the study was to evaluate the expression levels in OSMF, OSCC in the background of OSMF and OSCC using immunohistochemistry and also to correlate hTERT expression with clinicopathologic parameters. A total of 50 histopathologically diagnosed cases of 20 OSMF, 20 OSCC wherein 5 were OSCC in the background of OSMF and 10 Normal oral mucosae were retrieved from the departmental archives and subjected to immunohistochemical analysis of hTERT. The expression of hTERT increased from normal, OSMF, to OSCC with statistically significant differences in mean labelling score (LS). We also found a shift in cellular localization of stain where, normal mucosal tissues showed a nuclear stain unlike OSMF, where combined nuclear and cytoplasmic staining as noted. The tumor cells in OSCC showed predominant cytoplasmic staining. There was no correlation between hTERT expression and clinicopathological parameters of OSMF. However, a significant increase of hTERT expression was seen with increasing histological grading of OSCC. These results suggest the role of hTERT in the early event of malignant transformation of OSMF. Telomerase could be used as a potent diagnostic marker to identify high-risk group of OSMF.
C1 [Raju K, Lizbeth] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
[Haragannavar, C Vanishri] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
[Patil, Shankargouda] Jazan University, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral PathologyJazan, Saudi Arabia.
[Rao, S Roopa] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
[Nagaraj, Tejavathi] M.S. Ramaiah Dental College & Hospital, Department of Oral Medicine, Diagnosis and Radiology, Cholanagar, R.T. Nagar post, 560032 Bangalore, Karnataka, India.
[Augustine, Dominic] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
[Venkatesiah, S Sowmya] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
[Nambiar, Shwetha] Ramaiah University of Applied Sciences, Faculty of Dental Sciences, Department of Oral Pathology and Microbiology, M S R Nagar, 560054 Bangalore, Karnataka, India.
RP Patil, Sh (reprint author), Jazan University, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, Jazan, Saudi Arabia.
EM dr.ravipatil@gmail.com
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Gupta S, ReddyMVR, Harinath BC, 2004, Role of oxidative stress and antioxidants in aetiopathogenesis and management of oral submucous fibrosis. Indian J Clin Biochem 19:138–141. , DOI 10.1007/BF02872409
Akiyama M, Hideshima T, Hayashi T, Tai YT, Mitsiades CS, Mitsiades N, Chauhan D, Richardson P, Munshi NC, Anderson KC, 2003, Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res 63:18–21
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1573
EP 1582
DI 10.1007/s12253-019-00700-6
PG 10
ER
PT J
AU Liu, Q
Zhang, X
Tang, H
Liu, J
Fu, Ch
Sun, M
Zhao, L
Wei, M
Yu, Z
Wang, P
AF Liu, Qianqian
Zhang, Xiling
Tang, Haichao
Liu, Jinwei
Fu, Chen
Sun, Mingli
Zhao, Lin
Wei, Minjie
Yu, Zhaojin
Wang, Ping
TI Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AURKB; KIF18B; Clear cell renal cell carcinoma; Differentially expressed genes; Combined expression
ID AURKB; KIF18B; Clear cell renal cell carcinoma; Differentially expressed genes; Combined expression
AB Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three overexpressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.
C1 [Liu, Qianqian] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Zhang, Xiling] China Medical University, The Fourth Affiliated Hospital, Department of Urology, 110000 Shenyang, Liaoning, China.
[Tang, Haichao] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Liu, Jinwei] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Fu, Chen] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Sun, Mingli] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Zhao, Lin] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Wei, Minjie] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Yu, Zhaojin] China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, Liaoning, China.
[Wang, Ping] China Medical University, The Fourth Affiliated Hospital, Department of Urology, 110000 Shenyang, Liaoning, China.
RP Yu, Z (reprint author), China Medical University, School of Pharmacy, Department of Pharmacology, 110122 Shenyang, China.
EM yuzhaojincmu@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1583
EP 1594
DI 10.1007/s12253-019-00740-y
PG 12
ER
PT J
AU Chai, YSz
Peng, R
Zhang, R
Zhou, L
Pillay, N
Tay, HK
Badrick, T
Li, J
Horan, PM
AF Chai, Yee Sze
Peng, Rongxue
Zhang, Rui
Zhou, Li
Pillay, Nalishia
Tay, Hong Kwang
Badrick, Tony
Li, Jinming
Horan, P Martin
TI External Quality Assurance of Current Technology for the Testing of Cancer-Associated Circulating Free DNA Variants
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating free DNA (cfDNA); Next-generation sequencing; Digital PCR; External quality assurance; Liquid biopsy
ID Circulating free DNA (cfDNA); Next-generation sequencing; Digital PCR; External quality assurance; Liquid biopsy
AB Liquid biopsy testing is rapidly emerging as a diagnostic means of identifying circulating free DNA (cfDNA) disease-associated variants. However, the reporting of cfDNA variants remains inconsistent due in part to the application of multiple testing pipelines which raise uncertainty about current cfDNA detection efficiency. External quality assurance (EQA) programs are required to monitor, evaluate and help improve laboratory performance for cfDNA variant detection and in clinical interpretation. This study therefore evaluated the performance of diagnostic laboratories currently performing cfDNA testing in China, Australia and New Zealand. A total of 89 laboratories participated in this EQA program. Reference testing material comprised of cfDNA manufactured to contain six different genotypes in four different genes (EGFR, KRAS, BRAF, NRAS). The predicted genotypic variant allelic frequencies ranged between 0.5% - 2.5%. Proficiency testing used a z-score on the laboratory consensus allelic frequency data to compare laboratory performance for the detection of the different genotypes. Allelic frequency genotyping data were received from 88 of the 89 laboratories. Next generation sequencing and digital PCR testing platforms were primarily used by participants in this pilot EQA. The average consensus data for each cfDNA genotype identified allelic frequencies ranging between 0.39% - 4.4%. Z-score proficiency testing found that >92% of clinical laboratories were concordant for detecting the cfDNA variants. The data from this pilot study suggest that current cfDNA testing platforms can detect cfDNA allelic frequency variants from 0.39% and above with high levels of confidence. In addition, these data highlight the importance of laboratories enrolling on EQA programs so that proficiency in cfDNA diagnostic testing can be determined and potential sources of error identified and addressed.
C1 [Chai, Yee Sze] St Leonard’s, RCPAQAP Molecular GeneticsSydney, Australia.
[Peng, Rongxue] National Center of Gerontology, Beijing Hospital, National Center for Clinical LaboratoriesBeijing, China.
[Zhang, Rui] National Center of Gerontology, Beijing Hospital, National Center for Clinical LaboratoriesBeijing, China.
[Zhou, Li] National Center of Gerontology, Beijing Hospital, National Center for Clinical LaboratoriesBeijing, China.
[Pillay, Nalishia] St Leonard’s, RCPAQAP Molecular GeneticsSydney, Australia.
[Tay, Hong Kwang] St Leonard’s, RCPAQAP Molecular GeneticsSydney, Australia.
[Badrick, Tony] St Leonard’s, RCPAQAP Molecular GeneticsSydney, Australia.
[Li, Jinming] National Center of Gerontology, Beijing Hospital, National Center for Clinical LaboratoriesBeijing, China.
[Horan, P Martin] St Leonard’s, RCPAQAP Molecular GeneticsSydney, Australia.
RP Horan, PM (reprint author), St Leonard’s, RCPAQAP Molecular Genetics, Sydney, Australia.
EM martin.horan@rcpaqap.com.au
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van Veggel B, de Langen AJ, Hashemi SMS, Monkhorst K, Heideman DAM, Thunnissen E, Smit EF, 2018, Afatinib and cetuximab in four patients with EGFR exon 20 insertion-positive advanced NSCLC. J Thorac Oncol 13:1222–1226
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1595
EP 1603
DI 10.1007/s12253-019-00744-8
PG 9
ER
PT J
AU Ke, D
Wang, Q
Ke, Sh
Zou, L
Wang, Q
AF Ke, Dong
Wang, Qiushuang
Ke, Shaobo
Zou, Li
Wang, Qi
TI Long-Non Coding RNA SNHG16 Supports Colon Cancer Cell Growth by Modulating miR-302a-3p/AKT Axis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SNHG16; miR-302a-3p; AKT; Colon cancer; Cell growth
ID SNHG16; miR-302a-3p; AKT; Colon cancer; Cell growth
AB Small nucleolar RNA host gene 16 (SNHG16) is reported to be involved in the tumorigenesis of various kinds of tumors. SNHG16 expression was reported to be upregulated in colon cancer, however, the underlying mechanism of how SNHG16 affects the colon cancer development remains poorly elucidated. In our study, with the aim to identify the role of SNHG16 on colon cell proliferation, SNHG16 was overexpressed or knocked down in vitro, respectively. SNHG16 overexpression accelerated colon cancer cell growth, while cell growth ability was impaired in SNHG16 silencing cells. Furthermore, the starBase database predicted that miR-302a-3p was the target gene of SNHG16, which was supported by dual luciferase assay. The effect of promoting cell proliferation ability induced by SNHG16 overexpression could be partly reversed by co-transfection of miR- 302a-3p mimic. Application of the miRanda database indicated that AKT may be modulated by SNHG16, further evidenced by western blot and quantitative PCR assays. AKT overexpression could partly reverse the attenuated colon cancer cell growth caused by miR-302a-3p mimic transfection. Meanwhile, the combination of miR-302a-3p inhibitor and shAKT achieved the parallel result. In conclusion, our study revealed the SNHG16/miR-302a-3p/AKT axis might play a crucial role in colon cancer cell proliferation, thus participating in the process of colon cancer development.
C1 [Ke, Dong] Renmin Hospital of Wuhan University, Department of Gastrointestinal Surgery, 430060 Wuhan, Hubei, China.
[Wang, Qiushuang] Renmin Hospital of Wuhan University, Department of Gastrointestinal Surgery, 430060 Wuhan, Hubei, China.
[Ke, Shaobo] Renmin Hospital of Wuhan University, Center of Oncology, 430060 Wuhan, Hubei, China.
[Zou, Li] Renmin Hospital of Wuhan University, Department of Gastrointestinal Surgery, 430060 Wuhan, Hubei, China.
[Wang, Qi] Renmin Hospital of Wuhan University, Department of Gastrointestinal Surgery, 430060 Wuhan, Hubei, China.
RP Wang, Q (reprint author), Renmin Hospital of Wuhan University, Department of Gastrointestinal Surgery, 430060 Wuhan, China.
EM qiw@whu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1605
EP 1613
DI 10.1007/s12253-019-00743-9
PG 9
ER
PT J
AU Yang, P
Wang, Q
Liu, A
Zhu, J
Feng, J
AF Yang, Peipei
Wang, Qian
Liu, Aihua
Zhu, Jun
Feng, Jinzhou
TI ALKBH5 Holds Prognostic Values and Inhibits the Metastasis of Colon Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ALKBH5; Colon cancer; Invasion; Metastasis
ID ALKBH5; Colon cancer; Invasion; Metastasis
AB N6-methyladenosine (m6A) demethylase ALKBH5 is best known for modulating transcript modification in plenty of human malignancies, but its role in the progression of colon cancer is not well understood. In the present study, we identified the tumor repressive role of ALKBH5 in colon cancer. ALKBH5 was downregulated in human colon cancer tissues, where its decreased expression significantly correlated with distant metastasis and American Joint Committee on Cancer (AJCC) stage. ALKBH5 was also an independent prognostic indicator of overall survival and disease-free survival in colon cancer patients. Furthermore, functional studies established that overexpression of ALKBH5 inhibited colon cancer cells invasion in vitro and metastasis in vivo. These results indicated that ALKBH5 significantly inhibits tumor progression and serves as a potential therapeutic target for colon cancer.
C1 [Yang, Peipei] The First Affiliated Hospital of Anhui University of Science and Technology, Department of General Surgery, No. 203, Huaibin road, 232000 Huainan, Anhui Province, China.
[Wang, Qian] Shandong First Medical University & Shangdong Academy of Medical Sciences, Taian City Central Hospital, Department of Central Laboratory, 29 Longtan Road, Taishan District, 271000 Taian, Shandong Province, China.
[Liu, Aihua] Shandong First Medical University & Shangdong Academy of Medical Sciences, Taian City Central Hospital, Department of Central Laboratory, 29 Longtan Road, Taishan District, 271000 Taian, Shandong Province, China.
[Zhu, Jun] Hang Zhou Di’an Medical Laboratory, 329 Jinpeng Road, Xihu District, 310030 Hangzhou, Zhejiang Province, China.
[Feng, Jinzhou] The First Affiliated Hospital of Chongqing Medical University, Department of Neurology, 1 Youyi Road, Yuzhong District, 400016 Chongqing, China.
RP Feng, J (reprint author), The First Affiliated Hospital of Chongqing Medical University, Department of Neurology, 400016 Chongqing, China.
EM fengjinzhou@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1615
EP 1623
DI 10.1007/s12253-019-00737-7
PG 9
ER
PT J
AU Spachmann, JP
Azzolina, V
Weber, F
Evert, M
Eckstein, M
Denzinger, S
Burger, M
Otto, W
Breyer, J
AF Spachmann, J Philipp
Azzolina, Vanessa
Weber, Florian
Evert, Matthias
Eckstein, Markus
Denzinger, Stefan
Burger, Maximilian
Otto, Wolfgang
Breyer, Johannes
TI Loss of CHEK2 Predicts Progression in Stage pT1 Non-Muscle-Invasive Bladder Cancer (NMIBC)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-muscle-invasive bladder cancer; NMIBC; CHEK2; Smoking status; Progression
ID Non-muscle-invasive bladder cancer; NMIBC; CHEK2; Smoking status; Progression
AB Downregulation of checkpoint protein kinase 2 (CHEK2), which is involved in DNA repair, is associated with poorer outcome in various tumors. Little is known about the role of CHEK2 in urothelial carcinoma of the bladder (UCB). In the present study, we investigated the prognostic impact of CHEK2 protein expression in stage pT1 UCB. This retrospective, single-center analysis was carried out in a cohort of patients initially diagnosed with a pT1 UCB between 2007 and 2015. Immunohistochemical (IHC) staining of CHEK2 was performed. CHEK2 expression was correlated with recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) using Kaplan-Meier analysis and multivariable Cox regression analysis. The analysis included 126 patients (86%male, median age 71 years). Loss of immunohistochemical protein expression of CHEK2 (<10%) was associated with significantly worse PFS (p = 0.041). Likewise, CHEK2 loss identified a subgroup of patients with worse PFS in the high-risk groups with concomitant CIS (p = 0.044), multifocal tumors (p < 0.001) and tumor grading G3 according to WHO1973 (p = 0.009). Multivariable Cox regression analysis revealed both loss of CHEK2 expression (HR: 4.18, 95%-CI: 1.35–12.93; p = 0.013) and multifocal tumors (HR: 4.53, 95%-CI:1.29–15.92; p = 0.018) as the only predictive factors for progression. Loss of IHC expression of CHEK2 in pT1 UCB is an independent predictor for progression to muscle-invasive disease and is also associated with worse PFS. This could help to identify high-risk patients who would benefit from early cystectomy.
C1 [Spachmann, J Philipp] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
[Azzolina, Vanessa] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
[Weber, Florian] University of Regensburg, Institute of PathologyRegensburg, Germany.
[Evert, Matthias] University of Regensburg, Institute of PathologyRegensburg, Germany.
[Eckstein, Markus] Friedrich-Alexander-Universitat Erlangen-Nurnberg, University Hospital Erlangen, Institute of PathologyErlangen, Germany.
[Denzinger, Stefan] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
[Burger, Maximilian] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
[Otto, Wolfgang] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
[Breyer, Johannes] University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, Landshuter Str. 65, 93053 Regensburg, Germany.
RP Spachmann, JP (reprint author), University of Regensburg, Caritas St. Josef Medical Center, Department of Urology, 93053 Regensburg, Germany.
EM philipp.spachmann@ukr.de
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1625
EP 1632
DI 10.1007/s12253-019-00745-7
PG 8
ER
PT J
AU Pal, I
Szilagyi, B
Nagy, B
Pal, T
Hodosi, K
Illes,
Varoczy, L
AF Pal, Ildiko
Szilagyi, Bernadett
Nagy, Bela
Pal, Tibor
Hodosi, Katalin
Illes, Arpad
Varoczy, Laszlo
TI The Impact of Beta-Catenin and glutathione-S-transferase Gene Polymorphisms on the Treatment Results and Survival of Multiple Myeloma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiple myeloma; Cereblon; ß-catenin; Glutathione-S-transferase; Polymorphism; Personalized treatment
ID Multiple myeloma; Cereblon; ß-catenin; Glutathione-S-transferase; Polymorphism; Personalized treatment
AB Multiple myeloma (MM) is an incurable disease, however, novel therapeutic agents has significantly improved its prognosis. In this study we analyzed if polymorphisms in the genes of β-catenin and glutathione-S-transferase have affected the clinical course, treatment response and progression-free survival (PFS) of MM patients. Ninety-seven MM patients were involved who were administered immunomodulatory drug (Imid) or alkylating agent-based therapy. β-catenin (CTNNB1, rs4135385 A > G, rs4533622 A > C) and glutathione-S-transferase (GSTP1 105, GSTP1 114) gene polymorphisms were analyzed by Light SNiP assays. The distribution of CTNNB1 (rs4135385) AA, AG and GG genotypes were 48.4%, 47.4% and 4,1%, respectively. Patients with AA genotype were older than those who carried G allele (64.5 vs. 61.0 years of age, p < 0.05). Response to Imidbased therapies (p < 0.05) and PFS (p = 0.032) were significantly more favourable in the AA homozygous group. The other polymorphism(rs4533622) of β-catenin gene did not markedly influence these clinical parameters, althoughMMwas diagnosed at significantly younger age in subjects with CC genotype compared to AG/AA combined genotypes (59.1 vs. 65.7 years, p = 0.015). When GSTP1 polymorphisms were investigated, no such significant associations were observed. Our results demonstrate that the polymorphism of β-catenin gene (rs4135385) may be an independent predictive factor in MM.
C1 [Pal, Ildiko] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Szilagyi, Bernadett] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Nagy, Bela] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Pal, Tibor] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Hodosi, Katalin] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of Hematology, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Varoczy, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, H-4032 Debrecen, Hungary.
EM varoczy@internal.med.unideb.hu
CR Jaak Ph J, Klaus S, Andreas Vet al, 2018, Preventive, predictive, and personalized medicine for effective and affordable cancer care. EPMA Journal 9:113–123
Raza S, Safyan RA, Rosenbaum E, Bowman AS, Lentzsch S, 2017, Optimizing current and emerging therapies in multiple myeloma: a guide for the haematologist. Ther Adv Hematol 8:55–70
van Hengel J, Nollet F, Berx G, van Roy N, Speleman F, van Roy F, 1995, Assignment of the human beta-catenin gene, CTNNB1, to 3p22-p21.3 by fluorescence in situ hybridization. Cytogenet Cell Genet 70:68–70
Nollet F, Berx G, Molemans F, van Roy F, 1996, Genomic organization of the human beta-catenin gene, CTNNB1). Genomics. 32: 413–424
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1633
EP 1638
DI 10.1007/s12253-019-00747-5
PG 6
ER
PT J
AU Yao, Y
Pang, T
Cheng, Y
Yong, W
Kang, H
Zhao, Y
Wang, S
Hu, X
AF Yao, Yunhong
Pang, Tianyun
Cheng, Ying
Yong, Weiwei
Kang, Haixian
Zhao, Yi
Wang, Sen
Hu, Xinrong
TI Positive Correlative over-Expression between eIF4E and Snail in Nasopharyngeal Carcinoma Promotes its Metastasis and Resistance to Cisplatin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE eIF4E; Snail; NPC; EMT; Invasion; Metastasis
ID eIF4E; Snail; NPC; EMT; Invasion; Metastasis
AB EIF4E is the rate-limiting factor in the mRNA translation of specific set of oncogenes. Snail is the core transcription factor of epithelial-mesenchymal transition (EMT), a key step of cancer metastasis. The connection between the two oncoproteins has not been well established in the human cancer tissues and in nasopharyngeal carcinoma (NPC). Here we showed that the positive correlative over-expression was seen between eIF4E and Snail in NPC tissues, and the expression was significantly higher in the metastatic NPC than in the un-metastatic NPC. In NPC cells, eIF4E knockdown significantly reduced Snail mRNA and protein levels, increased the mRNA level of E-cad (a direct downstream gene of Snail and a negative EMT marker), attenuated the invasive ability of the cells, and sensitized the cells to cisplatin in invasion. In contrast, enforced the expression of eIF4E significantly increased Snail mRNA and protein levels, and promoted the invasive ability in NPC cells. Under the condition of the high eIF4E expression, Snail knockdown significantly increased E-cad mRNA level and weaken the invasive ability of NPC cells. Finally, eIF4E directly bound Snail mRNA for translation initiation displayed by the RIP assay. Therefore, the results firstly suggested that eIF4E enhanced the Snail expression in both transcription and translation manner in human cancer tissues and targeting the eIF4E/Snail axis might intervene with the EMT and metastasis of NPC. This finding provided a new clue for further understanding the metastatic mechanism of human cancers and for preventing and treating NPC metastasis.
C1 [Yao, Yunhong] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Pang, Tianyun] Guangdong Medical University, Department of Obstetrics and Gynecology, 523808 Dongguan, China.
[Cheng, Ying] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Yong, Weiwei] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Kang, Haixian] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Zhao, Yi] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Wang, Sen] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
[Hu, Xinrong] Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
RP Hu, X (reprint author), Guangdong Medical University, Cancer Research Institute, Department of Pathology, 523808 Dongguan, China.
EM huxinrong@163.com;404752528@qq.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1639
EP 1649
DI 10.1007/s12253-019-00733-x
PG 11
ER
PT J
AU Bozdag, Z
Tutar, E
Dizibuyuk, FO
Bakir, K
AF Bozdag, Zehra
Tutar, Ediz
Dizibuyuk, Faruk Omer
Bakir, Kemal
TI Monoclonal Caveolin 1 Expression in the Differential Diagnosis of Malignant Pleural Mesothelioma and Pulmonary Adenocarcinoma: Is it Useful?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveolin 1; Mesothelioma; Pulmonary adenocarcinoma
ID Caveolin 1; Mesothelioma; Pulmonary adenocarcinoma
AB In this study we aim to demonstrate the value of monoclonal Caveolin 1 expression in distinguishing between malignant pleural mesothelioma and pulmonary adenocarcinoma. Total of 129 cases, consisting of 68 cases of malignant pleural mesothelioma (51 epitheloid, 12 biphasic, and 5 sarcomatoid type) and 61 cases of pulmonary adenocarcinoma were examined and stained with monoclonal Caveolin-1. Caveolin 1 expression with a membranous and /or cytoplasmic pattern was detected only in 32.35% (n:22/68) of malignant pleural mesothelioma and 6.5% (n:4/61) of pulmonary adenocarcinoma cases. This finding suggests that the choice of poly/monoclonal antibody for Caveolin 1 in the differential diagnosis of malignant pleural mesothelioma and pulmonary adenocarcinoma is important.
C1 [Bozdag, Zehra] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Tutar, Ediz] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Dizibuyuk, Faruk Omer] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Bakir, Kemal] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
RP Bozdag, Z (reprint author), Gaziantep University, Faculty of Medicine, Department of Pathology, Gaziantep, Turkey.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1651
EP 1656
DI 10.1007/s12253-019-00751-9
PG 6
ER
PT J
AU Bozdag, Z
Tutar, E
Dizibuyuk, FO
Bakir, K
AF Bozdag, Zehra
Tutar, Ediz
Dizibuyuk, Faruk Omer
Bakir, Kemal
TI Correction to: Monoclonal Caveolin 1 Expression in the Differential Diagnosis of Malignant Pleural Mesothelioma and Pulmonary Adenocarcinoma: Is it Useful?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Correction to: Pathology & Oncology Research https://doi.org/10.1007/s12253-019-00751-9 The original version of this article unfortunately contained an error in Fig. 1. Cav-1 expression in MPM and PA cases failed to show the histopathological details in Fig. 1 due to technical problem. The figure with the proper sharpness and clarity is shown in the next page.
C1 [Bozdag, Zehra] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Tutar, Ediz] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Dizibuyuk, Faruk Omer] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
[Bakir, Kemal] Gaziantep University, Faculty of Medicine, Department of PathologyGaziantep, Turkey.
RP Bozdag, Z (reprint author), Gaziantep University, Faculty of Medicine, Department of Pathology, Gaziantep, Turkey.
EM zbozdagmd@gmail.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1657
EP 1658
DI 10.1007/s12253-020-00793-4
PG 2
ER
PT J
AU Kato, A
Kato, K
Miyazawa, H
Kobayashi, H
Noguchi, N
Kawashiri, Sh
AF Kato, Aki
Kato, Koroku
Miyazawa, Hiroki
Kobayashi, Hisano
Noguchi, Natsuyo
Kawashiri, Shuichi
TI Focal Adhesion Kinase (FAK) Overexpression and Phosphorylation in Oral Squamous Cell Carcinoma and their Clinicopathological Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Focal adhesion kinase; FAK; FAKpY397; p16; Oral squamous cell carcinoma; Prognosis
ID Focal adhesion kinase; FAK; FAKpY397; p16; Oral squamous cell carcinoma; Prognosis
AB Focal adhesion kinase (FAK) is involved in progression of various cancers, and FAK overexpression has been associated with cancer invasion and metastasis. However, the involvement of FAK expression in the clinicopathological malignancy of oral squamous cell carcinoma (OSCC) remains unknown. In addition, there is no consensus regarding the role of p16 expression in OSCC. In this study, the immunohistochemically measured expression of FAK, phosphorylated FAK (FAKpY397) and p16 expressions and their associations with clinicopathological features and 5-year survival rates were examined in surgical samples from 70 patients with primary OSCC. FAK and FAKpY397 were expressed at high levels in 42 cases (60.0%) and 34 cases (48.6%), respectively, and 9 cases (12.9%) were positive for p16. FAK expression was significantly correlated with local recurrence, subsequent metastasis, and the mode of invasion. FAKpY397 expression was significantly correlated with both N classification and the mode of invasion. p16 expression was significantly correlated with clinical stage only. Patients having high expression of FAK, FAKpY397, or both showed significantly worse prognosis, but p16 expression showed no significant relation to prognosis. The results suggested that overexpression and phosphorylation of FAK in OSCC may affect cancer progression, such as local invasion and lymph node metastasis, and thereby contribute to life prognosis.
C1 [Kato, Aki] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kato, Koroku] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Miyazawa, Hiroki] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kobayashi, Hisano] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Noguchi, Natsuyo] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kawashiri, Shuichi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
RP Kato, K (reprint author), Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 920-8641 Kanazawa, Japan.
EM k-koroku@oral.m.kanazawa-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1659
EP 1667
DI 10.1007/s12253-019-00732-y
PG 9
ER
PT J
AU Jing, W
Peng, R
Zhu, M
Lv, Sh
Jiang, Sh
Ma, J
Ming, L
AF Jing, Wei
Peng, Ruoyu
Zhu, Man
Lv, Shaogang
Jiang, Shitao
Ma, Junfen
Ming, Liang
TI Differential Expression and Diagnostic Significance of Pre-Albumin, Fibrinogen Combined with D-Dimer in AFP-Negative Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pre-albumin; Fibrinogen; D-Dimer; AFP-negative hepatocellular carcinoma; Diagnosis
ID Pre-albumin; Fibrinogen; D-Dimer; AFP-negative hepatocellular carcinoma; Diagnosis
AB Hepatocellular carcinoma (HCC) is one of the most malignant cancers with high morbidity and mortality. Nowadays, AFP-negative hepatocellular carcinoma (AFP-NHCC) has been found in many HCC patients and AFP analysis can’t be used to screen HCC in these cases. In this study, we have examined the expression patterns of pre-albumin (PA), fibrinogen, D-Dimer and their clinical significance in AFP-NHCC. We recruited 214 AFP-NHCC patients and 210 controls in the study. PA, fibrinogen and D-Dimer levels were detected by turbidimetry, clauss and immunoturbidimetry methods, respectively. Serum PA levels were significantly lower in AFP-NHCC (84.5 ± 24.7 mg/L) than that in the controls (240.6 ± 59.4 mg/L, P < 0.05). For plasma fibrinogen levels, there was no difference between the controls (2.9 ± 0.7 g/L) and AFP-NHCC (2.5 ± 0.7 g/L). Compared with AFP-NHCC (0.8 ± 0.2 mg/L), plasma D-Dimer levels were significantly lower in controls (0.1 ± 0.0 mg/L, P < 0.05). The levels of PA, fibrinogen and D-Dimer were significantly correlated with differentiation (P < 0.01), and the PA and D-Dimer values were correlated with TNM stage (P < 0.05). Moreover, PA levels were correlated with tumor size (P = 0.034). Receiver operating characteristic curve (ROC) analyses elaborated that combination of PA, fibrinogen and D-Dimer possessed a higher sensitivity (93.4%) for differentiating AFP-NHCC from the controls, but the diagnostic specificity was reduced due to the combination of fibrinogen. After adjusting for all significant outcome predictors of the univariate logistic regression analysis, low levels of PA and high levels of D-Dimer were remained independent unfavorable outcome predictors (P < 0.05). Our data suggested that the expression levels of PA, fibrinogen and D-Dimer played critical roles in AFP-NHCC tumorigenesis. Moreover, PA and D-Dimer might be considered as potential diagnostic indicators in AFP-NHCC.
C1 [Jing, Wei] the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
[Peng, Ruoyu] the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
[Zhu, Man] Huazhong University of Science and Technology, Tongji Medical College, the Central Hospital of Wuhan, Department of Medical Laboratory, 430000 Wuhan, China.
[Lv, Shaogang] the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
[Jiang, Shitao] the First Affiliated Hospital of Zhengzhou University, Henan Medical Key Laboratory of Molecular Imaging, 450000 Zhengzhou, China.
[Ma, Junfen] the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
[Ming, Liang] the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
RP Jing, W (reprint author), the First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan, Department of Clinical Laboratory, 450000 Zhengzhou, China.
EM xjw2009@yeah.net
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1669
EP 1676
DI 10.1007/s12253-019-00752-8
PG 8
ER
PT J
AU Xin, BCh
Wu, QSh
Jin, S
Luo, AH
Sun, DG
Wang, F
AF Xin, Bing-Chang
Wu, Qi-Shan
Jin, Song
Luo, Ai-Hua
Sun, De-Gang
Wang, Fang
TI Berberine Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Activating EGFR-MAPK-Runx2 Pathways
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Berberine; Dental pulp stem cells; Osteogenic differentiation; EGFR; MAPK
ID Berberine; Dental pulp stem cells; Osteogenic differentiation; EGFR; MAPK
AB Similar to the mesenchymal stem cells (MSCs), dental pulp stem cells (DPSCs) also have pluripotent differentiation characteristic and may be more ideal for tissue regeneration, especially in tooth regeneration engineering. However, bacterial infection may be a powerful obstacle. Berberine (BBR), known with antibacterial effects, was recently found to play functions in bone formation through promoting osteogenic differentiation from pluripotent stem cells. However, whether BBR also function in DPSCs osteogenic differentiation has not yet been reported. Primary DPSCs were isolated from dental pulp tissues extracted from human impacted mandibular third molars, and identified by flow cytometry for cell surface antigen molecules. A dexamethasone osteogenic medium was used to induce DPSCs osteogenic differentiation. BBR (1 μM and 5 μM) was pre-added to into medium, and then cell proliferation, spheroid formation and osteogenic differentiation capacities of DPSCs were analyzed, as well as the underlying molecules modulation mechanism. Flow cytometry identified that CD44, CD90, CD81 and CD105 positively expressed in the isolated hDPSCs, with CD34 and CD45 negatively expressed. BBR enhanced the cell proliferation of hDPSCs in a dose-dependent pattern, and promoted dexamethasone-induced osteogenic differentiation via enhancing Runx2 transcription factor activity followed by upregulating osteogenesis markers expression, whereas the adipogenic differentiation of hDPSCs was suppressed dramatically by BBR. The EGFR and MAPK pathways were activated by BBR, and inhibitors for these pathways significantly suppressed the osteogenic differentiation promotion of BBR. These results have revealed a novel mechanism that berberine might promote hDPSCs osteogenic differentiation through activating EGFR-MAPK-Runx2 signaling pathways.
C1 [Xin, Bing-Chang] Qingdao Stomatological Hospital, Department of Cariology and Endodontology, 266001 Qingdao, China.
[Wu, Qi-Shan] Tai’an City Central Hospital, Department of Stomatology, 271000 Taian, China.
[Jin, Song] Tai’an City Central Hospital, Department of Stomatology, 271000 Taian, China.
[Luo, Ai-Hua] Guizhou Provincial People’s Hospital, Department of Stomatology, 550002 Guiyang, China.
[Sun, De-Gang] Qingdao Stomatological Hospital, Department of Cariology and Endodontology, 266001 Qingdao, China.
[Wang, Fang] Qingdao Stomatological Hospital, Department of Pharmacy, No.17, Dexian Road, Shinan District, 266001 Qingdao, China.
RP Wang, F (reprint author), Qingdao Stomatological Hospital, Department of Pharmacy, 266001 Qingdao, China.
EM wangfang6525@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1677
EP 1685
DI 10.1007/s12253-019-00746-6
PG 9
ER
PT J
AU Ni, YH
Zhang, Xx
Lu, Zy
Huang, XF
Wang, ZY
Yang, Y
Dong, Ych
Jing, Y
Song, Y
Hou, YY
Hua, Zch
Hu, QG
AF Ni, Yan-Hong
Zhang, Xiao-xin
Lu, Zhan-yi
Huang, Xiao-Feng
Wang, Zhi-Yong
Yang, Yan
Dong, Ying-chun
Jing, Yue
Song, Yuxian
Hou, Ya-Yi
Hua, Zi-chun
Hu, Qin-Gang
TI Tumor-Infiltrating CD1a+ DCs and CD8+/FoxP3+ Ratios Served as Predictors for Clinical Outcomes in Tongue Squamous Cell Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Tongue squamous cell carcinoma; Tumor infiltrating immune cell; Clinical outcome; Diagnostic value
ID Tongue squamous cell carcinoma; Tumor infiltrating immune cell; Clinical outcome; Diagnostic value
AB Tumor-infiltrating immune cells engage in an extensive crosstalk with tumors and act as two-edged swords by inhibiting or promoting cancer growth. Therefore, identifying the density and prognostic values of tumor-infiltrating immune cells will provide valuable tips for cancer treatments. In this study, we identified the density of tumor inflammatory infiltrates and the number of tumor-infiltrating immune cells, including CD3+, CD4+, CD8+, FoxP3+ T cells and CD1a+ dendritic cells (DCs) in 153 tongue squamous cell carcinomas (TSCC). High inflammatory cell infiltration was associated with better overall survival (OS) and disease-free survival (DFS). Moreover, the number of CD3+, CD4+, FoxP3+ and CD1a+ cells were associated with tumor differentiation (P<0.001) and the number of FoxP3+, CD1a+ cells and CD8+/FoxP3+ ratios were also associated with tumor stage (P<0.01, P<0.01, P<0.05). In addition, patients with higher CD1a+ DCs had better OS and increased CD8+/FoxP3+ ratios were associated with improved OS and DFS (P = 0.037; P = 0.047; P = 0.033). In conclusion, our results indicated that tumorinfiltrating CD1a+ DCs and CD8+/FoxP3+ ratios were associated with favorable clinical outcomes but not independent prognostic factors for TSCC patients.
C1 [Ni, Yan-Hong] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Zhang, Xiao-xin] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Lu, Zhan-yi] Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial SurgeryNanjing, China.
[Huang, Xiao-Feng] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Wang, Zhi-Yong] Medical School of Nanjing University, Nanjing Stomatological Hospital, Department of Oral and Maxillofacial SurgeryNanjing, China.
[Yang, Yan] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Dong, Ying-chun] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Jing, Yue] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Song, Yuxian] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Hou, Ya-Yi] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Hua, Zi-chun] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
[Hu, Qin-Gang] Medical School, Nanjing University, Nanjing Stomatological Hospital, Central LaboratoryNanjing, China.
RP Hu, QG (reprint author), Medical School, Nanjing University, Nanjing Stomatological Hospital, Central Laboratory, Nanjing, China.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1687
EP 1695
DI 10.1007/s12253-019-00701-5
PG 9
ER
PT J
AU Wang, Y
Jiang, W
Li, C
Xiong, X
Guo, H
Tian, Q
Li, X
AF Wang, Yun
Jiang, Wangjie
Li, Cunjiang
Xiong, Xuanxuan
Guo, Hao
Tian, Qingzhong
Li, Xiangcheng
TI Autophagy Suppression Accelerates Apoptosis Induced by Norcantharidin in Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Autophagy; Norcantharidin; Cholangiocarcinoma; Apoptosis
ID Autophagy; Norcantharidin; Cholangiocarcinoma; Apoptosis
AB Norcantharidin is a cantharidin demethylated analog with antitumor effects in many tumors, including cholangiocarcinoma. Autophagy suppression is known to increase chemosensitivity in cholangiocarcinoma. This study aimed to determine whether autophagy suppression accelerates apoptosis induced by norcantharidin in human cholangiocarcinoma cells. The human cholangiocarcinoma cell line QBC939 was incubated in RPMI 1640 medium with or without norcantharidin. Autophagy was induced using HBSS media with Ca2+ and Mg2+ supported by 10mMHEPES or suppressed by treatment with 3-MA or transfection with siRNA against Atg5. The comparison was drawn between these conditions in mitochondrial membrane potential disturbance, the levels of reactive oxygen species (ROS), apoptotic proteins, and apoptosis. Cholangiocarcinoma cell apoptosis was accelerated by norcantharidin. Autophagy suppression up-regulated norcantharidin’s pro-apoptotic effect, but autophagy induction weakened it. As apoptosis was accelerated, ROS production was up-regulated. Bax protein expression, cytochrome c levels and localization, mitochondrial membrane disturbance, and the levels of caspase-9, caspase-3, and cleaved PARP were higher when autophagy was suppressed, and all of those were down-regulated when autophagy was induced. To sum up, it was found that norcantharidin induced cholangiocarcinoma cell death, and autophagy suppression enhanced the pro-apoptotic action of norcantharidin, which appears to involve the mitochondrial apoptosis pathway activation and ROS generation.
C1 [Wang, Yun] The First Affiliated Hospital of Nanjing Medical University, Department of Liver Transplantation Center, 300 Guang Zhou Road, 210029 Nanjing, Jiangsu, China.
[Jiang, Wangjie] The First Affiliated Hospital of Nanjing Medical University, Department of Liver Transplantation Center, 300 Guang Zhou Road, 210029 Nanjing, Jiangsu, China.
[Li, Cunjiang] The Affiliated Hospital of the Southeast University Medical School (Xu zhou), Xuzhou City Central Hospital, Department of Thoracic Surgery, 199 Jiefang South Road, 221009 Xuzhou, Jiangsu, China.
[Xiong, Xuanxuan] The Affiliated Hospital of the Southeast University Medical School (Xu zhou), Xuzhou City Central Hospital, Department of Gastroenterology 2, 199 Jiefang South Road, 221009 Xuzhou, Jiangsu, China.
[Guo, Hao] The Tumor Research Institute of the Southeast University (Xu zhou), Xuzhou City Central Hospital, The Affiliated Hospital of the Southeast University Medical School (Xu zhou), Department of Oncological Surgery, 199 Jiefang South Road, 221009 Xuzhou, Jiangsu, China.
[Tian, Qingzhong] The Tumor Research Institute of the Southeast University (Xu zhou), Xuzhou City Central Hospital, The Affiliated Hospital of the Southeast University Medical School (Xu zhou), Department of Oncological Surgery, 199 Jiefang South Road, 221009 Xuzhou, Jiangsu, China.
[Li, Xiangcheng] The First Affiliated Hospital of Nanjing Medical University, Department of Liver Transplantation Center, 300 Guang Zhou Road, 210029 Nanjing, Jiangsu, China.
RP Li, X (reprint author), The First Affiliated Hospital of Nanjing Medical University, Department of Liver Transplantation Center, 210029 Nanjing, China.
EM drxcli@njmu.edu.cn
CR Walden D, Kunnimalaiyaan S, Sokolowski K, Clark TG, Kunnimalaiyaan M, 2017, Antiproliferative and apoptotic effects of xanthohumol in cholangiocarcinoma. Oncotarget 8:88069– 88078
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1697
EP 1707
DI 10.1007/s12253-019-00719-9
PG 11
ER
PT J
AU Kong, J
Chen, X
Wang, J
Li, J
Xu, F
Gao, Sh
Yu, H
Qian, B
AF Kong, Jinyu
Chen, Xiaojie
Wang, Jian
Li, Jingxin
Xu, Fangxiu
Gao, Shegan
Yu, Herbert
Qian, Biyun
TI Genetic Polymorphisms in the Vitamin D Pathway and Non-small Cell Lung Cancer Survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Vitamin D pathway; Single nucleotide polymorphism; Genetic susceptibility; Prognosis
ID Non-small cell lung cancer; Vitamin D pathway; Single nucleotide polymorphism; Genetic susceptibility; Prognosis
AB Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.
C1 [Kong, Jinyu] The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Cancer Institute, 471003 Luoyang, China.
[Chen, Xiaojie] Henan University of Science and Technology, The First Affiliated Hospital, and College of Clinical Medicine, 471003 Luoyang, Henan, China.
[Wang, Jian] Henan University of Science and Technology, The First Affiliated Hospital, and College of Clinical Medicine, Department of Image Diagnoses, 471003 Luoyang, China.
[Li, Jingxin] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
[Xu, Fangxiu] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy, 300060 Tianjin, China.
[Gao, Shegan] The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Cancer Institute, 471003 Luoyang, China.
[Yu, Herbert] University of Hawaii Cancer Center, Epidemiology Program, 701 Ilalo Street, 96813 Honolulu, HI, USA.
[Qian, Biyun] Shanghai Jiao Tong University School of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Hongqiao International Institute of Medicine, 227 South Chongqing Road, 200025 Shanghai, China.
RP Qian, B (reprint author), Shanghai Jiao Tong University School of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Hongqiao International Institute of Medicine, 200025 Shanghai, China.
EM qianbiyun@shsmu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1709
EP 1715
DI 10.1007/s12253-019-00702-4
PG 7
ER
PT J
AU Cserni, D
Zombori, T
Stajer, A
Rimovszki, A
Cserni, G
Barath, Z
AF Cserni, Dorottya
Zombori, Tamas
Stajer, Anette
Rimovszki, Annamaria
Cserni, Gabor
Barath, Zoltan
TI Immunohistochemical Characterization of Reactive Epithelial Changes in Odontogenic Keratocysts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Odontogenic keratocyst; Immunohistochemistry; bcl2; Cytokeratin 10; Cytokeratin 17; Cytokeratin 19
ID Odontogenic keratocyst; Immunohistochemistry; bcl2; Cytokeratin 10; Cytokeratin 17; Cytokeratin 19
AB Odontogenic keratocysts (OKCs) have a diagnostic thin epithelial lining characterised by a linear epithelial connective tissue interface generally lacking inflammatory changes, basal palisading of the nuclei and a wavy parakeratotic layer on the surface. This typical epithelium may convert to a thicker non-keratinizing one with rete pegs and a relatively flat surface after operative decompression. The aim was to characterize this type of epithelial change by immunohistochemistry for bcl2, keratin17, 10 and 19. Eleven out of 33 archived OKCs demonstrated an altered epithelium related to previous biopsy, decompressing drainage or inflammation. The typical basal bcl2 staining was lost in 10/11 cases; transepithelial CK17 was lost or markedly reduced in 9/11 cases. CK10 displayed a segmental upper layer staining in OKCs, and its loss or partial loss in the altered epithelium did not differ from negative areas of OKCs. CK19 displayed various staining patterns in the altered epithelium from lost to maintained in a patchy transepithelial distribution, the latter of which did not differ from the typical OKC staining pattern. Three of four nonkeratinizing epithelial linings with basal palisading displayed immunostaining reminiscent of typical OKC epithelium. The lack of a typical epithelium is not sufficient to exclude the diagnosis of OKC if the sampling is not generous (e.g. biopsy), and the presence of non-keratinizing epithelium with basal palisading and an immunophenotype characteristic of OKC (basal bcl2, patchy or diffuse CK17 and upper layer CK10 positivity) may be consistent with the OKC diagnosis even in the absence of typical epithelial lining.
C1 [Cserni, Dorottya] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
[Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1, H-6725 Szeged, Hungary.
[Stajer, Anette] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
[Rimovszki, Annamaria] Bacs-Kiskun County Hospital, Department of Pathology, Nyiri ut 38, H-6000 Kecskemet, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1, H-6725 Szeged, Hungary.
[Barath, Zoltan] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
RP Cserni, G (reprint author), University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
EM cserni@freemail.hu
CR Pogrel MA, 2015, Keratocystic odontogenic tumour, KCOT, - an odyssey. Int J Oral Maxillofac Surg 44:1565–1568
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August M, Faquin WC, Troulis M, Kaban LB, 2003, Dedifferentiation of odontogenic keratocyst epithelium after decompression. J Oral Maxillofac Surg 61:678–683
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1717
EP 1724
DI 10.1007/s12253-019-00749-3
PG 8
ER
PT J
AU Li, J
Duan, H
Xuan, F
Zhao, E
Huang, M
AF Li, Jia
Duan, Haoyan
Xuan, Fan
Zhao, Erhu
Huang, Mengying
TI CDGSH Iron Sulfur Domain 2 Deficiency Inhibits Cell Proliferation and Induces Cell Differentiation of Neuroblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CDGSH iron sulfur domain 2; Neuroblastoma; Cell proliferation; Tumorigenesis; Differentiation
ID CDGSH iron sulfur domain 2; Neuroblastoma; Cell proliferation; Tumorigenesis; Differentiation
AB CDGSH iron sulfur domain 2 (CISD2) is reported to be highly expressed in several cancers, but the role of it in neuroblastoma has not been identified yet. Here, for the first time, we show that CISD2 is involved in neuroblastoma tumorigenesis and regulates neuroblastoma cell proliferation and differentiation. We found that high CISD2 expression correlated significantly with poor outcome of neuroblastoma patients, as well as advanced neuroblastoma tumor stages. Knockdown of CISD2 greatly repressed neuroblastoma cell proliferation and tumorigenesis both in vitro and in vivo. Further investigation showed that CISD2 deficiency resulted in cell cycle arrest in G1 phase and induced cell differentiation of neuroblastoma. Several Cyclins and Cyclin-Dependent Kinases (CDKs) were down-regulated by CISD2 knockdown, indicating that CISD2 probably regulates cell cycle through those genes. Together, we provide evidence that CISD2 is an indicator for neuroblastoma patients prognosis and is indispensable for neuroblastoma cell proliferation and tumorigenesis; CISD2 deficiency can induce neuroblastoma cell cycle arrest and differentiation. These findings suggest that CISD2 could work as a novel and potential therapeutic target for neuroblastoma treatment.
C1 [Li, Jia] Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
[Duan, Haoyan] Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
[Xuan, Fan] Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
[Zhao, Erhu] Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
[Huang, Mengying] Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
RP Huang, M (reprint author), Southwest University, State Key Laboratory of Silkworm Genome Biology, 400716 Chongqing, China.
EM mengyingh90@gmail.com
CR Brodeur GM, 2003, Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203–216
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PaddockML,Wiley SE, Axelrod HL, Cohen AE, RoyM, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA, 2007, MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A 104(36):14342–14347
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Yang L, Hong S, Wang Y, He Z, Liang S, Chen H, He S, Wu S, Song L, Chen Y, 2016, A novel prognostic score model incorporatingCDGSH iron sulfur domain2, CISD2, predicts risk of disease progression in laryngeal squamous cell carcinoma. Oncotarget 7(16):22720–22732
Sohn YS, Tamir S, Song L, Michaeli D, Matouk I, Conlan AR, Harir Y, Holt SH, Shulaev V, Paddock ML, Hochberg A, Cabanchick IZ, Onuchic JN, Jennings PA, Nechushtai R, Mittler R, 2013, NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci U S A 110(36):14676– 14681
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Eriksson KS, Zhang SW, Lin L, Lariviere RC, Julien JP, Mignot E, 2008, The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse. BMC Neurosci 9 23. Kageyama R, Ishibashi M, Takebayashi K, Tomita K, 1997, bHLH transcription factors and mammalian neuronal differentiation. Int J Biochem Cell Biol 29(12):1389–1399 24. Tamir S, Zuris JA, Agranat L, Lipper CH, Conlan AR,Michaeli D, Harir Y, Paddock ML, Mittler R, Cabantchik ZI, Jennings PA, Nechushtai R, 2013, Nutrient-deprivation autophagy factor-1, NAF-1): biochemical properties of a novel cellular target for antidiabetic drugs. PLoS One 8(5):e61202 25. Huang MY, Xuan F, Liu W, Cui HJ, 2017, MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation. Oncogene 36(3):387–396 26. Murray AW, 1992, Creative blocks - cell-cycle checkpoints and feedback controls. Nature 359(6396):599–604 27. Evans AE, D'Angio GJ, Randolph J, 1971, A proposed staging for children with neuroblastoma. Children's cancer study group a. Cancer 27(2):374–378 28. Haas D, Ablin AR, Miller C, Zoger S, Matthay KK, 1988, Complete pathologic maturation and regression of stage IVS neuroblastoma without treatment. Cancer 62(4):818–825 29. Westermark UK, Wilhelm M, Frenzel A, Henriksson MA, 2011, The MYCN oncogene and differentiation in neuroblastoma. Semin Cancer Biol 21(4):256–266 30. Xuan F, Huang M, Liu W, Ding H, Yang L, Cui H, 2016, Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1. Neuro-Oncology 18(6):819–829 31. Yang L, Huang M, Tan J, Hou J, He J,Wang F, Cui H, Yi L, 2017, Transcriptional co-activator with PDZ-binding motif overexpression promotes cell proliferation and transcriptional co-activator with PDZ-binding motif deficiency induces cell cycle arrest in neuroblastoma. Oncol Lett 13(6):4295–4301 32. Xuan F, Huang M, Zhao E, Cui H, 2018)MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishingDNA damage response. Cell Death Dis 9(11):1062
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1725
EP 1733
DI 10.1007/s12253-019-00753-7
PG 9
ER
PT J
AU Krishnamurthy, K
Sriganeshan, V
AF Krishnamurthy, Kritika
Sriganeshan, Vathany
TI Pancreatic Intraepithelial Neoplasia (PanIN) as a Morphologic Marker of Pancreatobiliary Type of Ampullary Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pancreatic intraepithelial neoplasia (pan-IN); Ampullary adenocarcinoma and its sub-types; Pancreatic adenocarcinoma; CDX2
ID Pancreatic intraepithelial neoplasia (pan-IN); Ampullary adenocarcinoma and its sub-types; Pancreatic adenocarcinoma; CDX2
AB The classification of ampullary adenocarcinoma into intestinal and pancreatobiliary sub-types has been found to be important in predicting prognosis and determining therapeutic strategy. Due to considerable inter-observer variability in sub-typing based solely on morphology, higher frequency of poorly differentiated cancers and low incidence of the disease, the histomorphologic classification of ampullary adenocarcinoma remains one of the grey zones in surgical pathology. Pan-IN is a well recognized precursor to pancreatic adenocarcinoma. Three studies have shown concurrent Pan-IN in patients with ampullary carcinoma, but their association with the two sub-types has not yet been reported. Fourteen cases of surgical resection for ampullary adenocarcinoma were retrieved from the archives. The cases were classified into two groups based on the presence or absence of concomitant Pan-IN. All the cases were stained for CK7, CK 20, Villin and CDX 2 and were classified as intestinal or pancreatobiliary types based on the staining pattern. All the 10 cases with Pan-IN stained negative for CDX2 and were classified as pancreatobiliary type (p = 0.01).Of the cases without Pan-IN, 3 were classified as intestinal sub-type based on morphology and CDX2 positivity and 1 was classified as pancreatobiliary type. Concomitant Pan-IN was present in 91% of pancreatobiliary type of ampullary adenocarcinoma. The grade of Pan-IN did not influence the grade or stage of the adenocarcinoma (p > 0.05). The co-occurrence of Pan-IN in a high percentage of the pancreatobiliary sub-type and its complete absence in the intestinal sub-type may serve as a strong differentiator between the two sub-types.
C1 [Krishnamurthy, Kritika] Mount Sinai Medical Center, Arkadi M Rywlin Department of Pathology and Laboratory Medicine, 4300Alton road, Suite 2400, 33140 Miami Beach, FL, USA.
[Sriganeshan, Vathany] Mount Sinai Medical Center, Arkadi M Rywlin Department of Pathology and Laboratory Medicine, 4300Alton road, Suite 2400, 33140 Miami Beach, FL, USA.
RP Krishnamurthy, K (reprint author), Mount Sinai Medical Center, Arkadi M Rywlin Department of Pathology and Laboratory Medicine, 33140 Miami Beach, USA.
EM kritikakrishnamurthy@yahoo.com
CR Albores-Saavedra J, Schwartz AM, Batich K, Henson DE, 2009, Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program. J Surg Oncol 100:598–605
Benhamiche AM, Jouve JL, Manfredi S, Prost P, Isambert N et al, 2000, Cancer of the ampulla of Vater: results of a 20-year population- based study. Eur J Gastroenterol Hepatol 12:75–79
Winter JM, Cameron JL, Olino K, Herman JM, Jong MC et al, 2010, Clinicopathologic analysis of ampullary neoplasms in 450 patients: implications for surgical strategy and long-term prognosis. J Gastrointest Surg 14:379–387
Kimura W, Futakawa N, Yamagata S, Wada Y, Kuroda A, Muto T, Esaki Y, 1994, Different clinicopathologic findings in two histologic types of carcinoma of papilla ofVater. Jpn J Cancer Res 85(2): 161–166
Bronsert P, Kohler I,Werner M, Makowiec F, Kuesters S, Hoeppner J, Hopt UT, Keck T, Bausch D, Wellner UF, 2013, Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin. BMC Cancer 13:428
Ruemmele P, Dietmaier W, Terracciano L, Tornillo L, Bataille F et al, 2009, Histopathologic features and microsatellite instability of cancers of the papilla of Vater and their precursor lesions. Am J Surg Pathol 33:691–704
Albores-Saavedra J, Henson DE, Klimstra DS, 2000, Malignant tumors of the ampulla. In:Tumors of the gallbladder extrahepatic bile ducts and ampulla of vater Armed Forces Institute of Pathology. Washington D.C, 259–316
Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, Clausen OPF, Gladhaug IP, 2008, Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma. BMCCancer 8:170
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Chang DK, Jamieson NB, Johns AL, 2013, Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of Vater. J Clin Oncol 31:1348–1356
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Agoff SN, Crispin DA, Bronner MP, Dail DH, Hawes SE et al, 2001, Neoplasms of the ampulla of Vater with concurrent pancreatic intraductal neoplasia: a histological and molecular study. Mod Pathol 14:139–143
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Zhou H, Schaefer N, Wolff M, Fischer H, 2004, Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol 28:875–882
Fischer HP, Zhou H, 2000, Pathologie der Papilla Vateri. In: Doerr W, Seifert G, Uehlinger E, eds, Spezielle Pathologische Anatomie: Pathologie der Leber und der Gallenwege, 2nd edn. Springer, Berlin Heidelberg New York Tokyo, pp 1219–1257
Sessa F, Furlan D, Zampatti C, Carnevali I, Franzi F, Capella C, 2007, Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability. Virchows Arch 451:649–657
Schueneman A, Wang H, Soifer HS, Schnabel CA, Wolff RA, Varadhachary GR, Overman MJ, 2014, Molecular classification of ampullary adenocarcinoma: comparative prognostic performance of the 92-gene assay versus histomolecular analysis. J Clin Oncol 32(15):4141–4141
Perkins G, Svrcek M, Bouchet-Doumenq C, Voron T, Colussi O, Debove C, et al., 2019, Can we classify ampullary tumours better? Clinical, pathological and molecularfeatures. Results of an AGEO study. Br J Cancer [Epub ahead of print]
Jeong BK, Sung YN, Kim SJ, An S, Park H, Hwang HS, Kang HJ, Lee JH, Song KB, Kim KP, Hwang DW, Lee SS, Kim SC, Hong SM, 2019, High-grade precursor lesions can be used as surrogate markers to identify the epicenter of periampullary carcinomas.Hum Pathol 84:92–104
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1735
EP 1739
DI 10.1007/s12253-019-00754-6
PG 5
ER
PT J
AU Zhang, X
Bu, R
Liu, Z
Wu, B
Bai, S
AF Zhang, Xuanyu
Bu, Renge
Liu, Zeqi
Wu, Bin
Bai, Song
TI Development and Validation of a Model for Predicting Intravesical Recurrence in Organ-confined Upper Urinary Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy: a Retrospective Study in One Center with Long-term Follow-up
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Intravesical recurrence; Upper urinary tract urothelial carcinoma; Radical nephroureterectomy; Retrospective study
ID Intravesical recurrence; Upper urinary tract urothelial carcinoma; Radical nephroureterectomy; Retrospective study
AB Although radical nephroureterectomy is the standard treatment method for upper urinary tract urothelial carcinoma, it is associated with a high risk of intravesical recurrence. There are no models for predicting IVR after RNU in patients with organ-confined UTUC. Therefore, we developed and validated a model for postoperative prediction of IVR after RNU. The development cohort consisted of 416 patients who underwent RNU with bladder cuff excision at our center between 1 January 2007 and 31December 2015. Patient clinicopathologic data were recorded. Multivariate Cox proportional hazard ratio regression was used to build a predictive model with regression coefficients, backward step-wise selection was applied, and the likelihood ratio test with Akaike’s information criterion was used as the stopping rule. An independent cohort consisting of 152 consecutive patients from 1 January 2016 and 31 December 2017 was used for validation. The performance of this predictive model was assessed with respect to discrimination, calibration, and clinical usefulness. The predictors in this model included tumor stage, tumor diameter, tumor location, and tumor grade. In the validation cohort, the model showed good discrimination, with a concordance index of 0.689 (95% CI, 0.629 to 0.748) and good calibration. Decision curve analysis demonstrated that the model was also clinically useful. This study presents a good model that may facilitate individualized postoperative prediction of IVR after RNU in patients with organ-confined UTUC, and thus, may help improve postoperative strategies and facilitate treatment outcomes.
C1 [Zhang, Xuanyu] ShengJing Hospital of China Medical University, Department of Urology, 36 Sanhao Street, 110004 Shenyang, Liaoning, China.
[Bu, Renge] ShengJing Hospital of China Medical University, Department of Urology, 36 Sanhao Street, 110004 Shenyang, Liaoning, China.
[Liu, Zeqi] ShengJing Hospital of China Medical University, Department of Urology, 36 Sanhao Street, 110004 Shenyang, Liaoning, China.
[Wu, Bin] ShengJing Hospital of China Medical University, Department of Urology, 36 Sanhao Street, 110004 Shenyang, Liaoning, China.
[Bai, Song] ShengJing Hospital of China Medical University, Department of Urology, 36 Sanhao Street, 110004 Shenyang, Liaoning, China.
RP Bai, S (reprint author), ShengJing Hospital of China Medical University, Department of Urology, 110004 Shenyang, China.
EM baisongcmu@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1741
EP 1748
DI 10.1007/s12253-019-00748-4
PG 8
ER
PT J
AU Andras, Cs
Bodoki, L
Nagy-Vincze, M
Griger, Z
Csiki, E
Danko, K
AF Andras, Csilla
Bodoki, Levente
Nagy-Vincze, Melinda
Griger, Zoltan
Csiki, Emese
Danko, Katalin
TI Retrospective Analysis of Cancer-Associated Myositis Patients over the Past 3 Decades in a Hungarian Myositis Cohort
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer-associated myositis (CAM); Dermatomyositis (DM); Polymyositis (PM); Cancer; Muscle weakness
ID Cancer-associated myositis (CAM); Dermatomyositis (DM); Polymyositis (PM); Cancer; Muscle weakness
AB Association between cancer and myositis has been extensively reported and malignancy is a potentially life-threating complication in myositis. In this retrospective study authors give an overview of Hungarian cancer-associated myositis (CAM) patients treated at a single centre managing 450 myositis patients. All patients were diagnosed according to Bohan and Peter. Statistical analysis of disease onset, age, sex, muscle, skin and extramuscular symptoms, muscle enzymes, presence of antibodies, treatment and prognosis was performed. 43 patients could be considered as having CAM. 83.72% had cancer within one year of diagnosis of myositis. Most common localizations were ductal carcinoma of breast and adenocarcinoma of lung. Significant differences were observed between CAM and the non-CAM control patients: DM:PM ratio was 2.31:1 vs. 0.87:1, respectively (p = 0.029), age at diagnosis was 56.60 ± 12.79 vs. 38.88 ± 10.88 years, respectively (p < 0.001). Tumour-treatment was the following: surgical removal in 55.81%, chemotherapy in 51.1%, radiotherapy in 39.53%, hormone treatment in 18.6%, combination therapy in 51.16% of patients. Muscle enzyme levels of patients undergoing surgery were significantly reduced after intervention. 36 patients died (83.72%); 25 DM(83.33%) and 11 PM patients (84.62%); 5 years survival was 15.4% for PM and 27.5% for DM. This study demonstrates that DM, distal muscle weakness, asymmetric Raynaud’s phenomenon, older age, ANA-negativity are risk factors for developing malignancy and polymyositis patients have less chance of long-lasting survival. It is very important to think about cancer and follow every single myositis patient in the clinical routine because survival rate of CAM is very poor.
C1 [Andras, Csilla] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Bodoki, Levente] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Nagy-Vincze, Melinda] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Griger, Zoltan] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Csiki, Emese] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
[Danko, Katalin] University of Debrecen, Faculty of Medicine, Department of Internal MedicineDebrecen, Hungary.
RP Bodoki, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Debrecen, Hungary.
EM bodoki.levente@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1749
EP 1755
DI 10.1007/s12253-019-00756-4
PG 7
ER
PT J
AU Guo, JL
Tang, T
Li, JH
Yang, YH
Zhang, L
Quan, Y
AF Guo, Jun-Liang
Tang, Tian
Li, Jin-Hong
Yang, Yi-Hong
Zhang, Long
Quan, Yi
TI LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; HEIH; Paclitaxel resistance; MAPK signaling pathway
ID Endometrial cancer; HEIH; Paclitaxel resistance; MAPK signaling pathway
AB This study aimed to investigate the function of lncRNA HEIH on promoting endometrial cancer cells’ tolerance of paclitaxel (PTX). LncRNA HEIH expression was measured by QRT-PCR in endometrial cancer tissues, human healthy tissues and cell lines. The PTX-resistant endometrial cancer cells (Ishikawa-RE and HHUA-RE) were intermittently exposed to increase concentrations of PTX and were constructed as evidenced by MTT assay. Besides, the specific siRNA of HEIH (siHEIH) and pcDNA3.1-HEIH plasmid transfection were utilized to alter the expression of HEIH in the cells and investigate the effects of HEIH on resistance to PTX in endometrial cancer cells. Moreover, MTT, colony formation and apoptosis analysis were taken advantage to evaluate cell viability and proliferation when treated with PTX. Then, differential genes in PTX-resistant and HEIH knock-down PTX-resistant endometrial cancer cells were screened out by microarray analysis. Finally, gene-set enrichment analysis was used to predict the promising signaling pathway of HEIH and western blotting analysis were performed to verify the relevant genes expression of MAPK signaling pathway. LncRNA HEIH, the dysregulation of which involved in production of drug-resistance, was overexpressed in PTX-resistant endometrial cancer cells. Up-regulating HEIH would activate MAPK pathway, promote chemo-resistance of endometrial cancer cells and enhance cell proliferation and viability, whereas silencing HEIH depressed the MAPK signaling pathway, contributed to restoring chemo-sensitivity to PTX and repressed cell physiological process. Down-regulating lncRNA HEIH expression reversed the PTX-resistance of endometrial cancer cells through MAPK signaling pathway.
C1 [Guo, Jun-Liang] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
[Tang, Tian] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
[Li, Jin-Hong] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
[Yang, Yi-Hong] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
[Zhang, Long] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
[Quan, Yi] West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, No.20 Section 3, Renmin South Road, 610041 Chengdu, Sichuan, China.
RP Quan, Y (reprint author), West China Second University Hospital, Sichuan University, West China Institute of Women and Children’s Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Laboratory of Molecular Translational Medicine, 610041 Chengdu, China.
EM quanyi516@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1757
EP 1766
DI 10.1007/s12253-019-00718-w
PG 10
ER
PT J
AU Somoracz,
Kuthi, L
Micsik, T
Jenei, A
Hajdu, A
Vrabely, B
Raso, E
Sapi, Z
Bajory, Z
Kulka, J
Ivanyi, B
AF Somoracz, Aron
Kuthi, Levente
Micsik, Tamas
Jenei, Alex
Hajdu, Adrienn
Vrabely, Brigitta
Raso, Erzsebet
Sapi, Zoltan
Bajory, Zoltan
Kulka, Janina
Ivanyi, Bela
TI Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Clear cell carcinoma; Clear cell papillary carcinoma; Cytokeratin 7-positivity; Differential diagnosis; VHL gene
ID Clear cell carcinoma; Clear cell papillary carcinoma; Cytokeratin 7-positivity; Differential diagnosis; VHL gene
AB Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary architecture were analyzed retrospectively with immunohistochemical and genetic markers to gain more experience with the differential diagnosis of such cases. All samples coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation. The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic disease was not observed. In summary, the VHL abnormalities distinguished the subset of CCRCC with diffuse CK7- positivity and no 3p loss from cases of CCPRCC.
C1 [Somoracz, Aron] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Kuthi, Levente] University of Szeged, Department of PathologySzeged, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jenei, Alex] University of Szeged, Department of PathologySzeged, Hungary.
[Hajdu, Adrienn] University of Szeged, Department of PathologySzeged, Hungary.
[Vrabely, Brigitta] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Bajory, Zoltan] University of Szeged, Department of UrologySzeged, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Ivanyi, Bela] University of Szeged, Department of PathologySzeged, Hungary.
RP Somoracz, (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM somoracz14@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1767
EP 1776
DI 10.1007/s12253-019-00757-3
PG 10
ER
PT J
AU Steppert, C
Krugmann, J
Sterlacci, W
AF Steppert, Claus
Krugmann, Jens
Sterlacci, William
TI Simultaneous endocrine expression and loss of melanoma markers in malignant melanoma metastases, a retrospective analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neuroendocrine expression; Melanoma metastases; Loss of melanoma markers
ID Neuroendocrine expression; Melanoma metastases; Loss of melanoma markers
AB Malignant melanoma metastases are chameleons of histopathology. In 4 primary malignant melanomas and 20 melanoma metastases expression of S-100, HMB-45 and melan-A as melanoma markers and CD56, synaptophysin and chromogranin-A as neuroendocrine markers was retrospectively analyzed. While all primary tumors expressed all 3 melanoma markers 7/20 of melanoma metastases had lost at least one melanoma marker, one had lost all three markers. Conversely about half of the samples stained for CD56, only 6/20metastases were negative for all 3 neuroendocrine markers. None expressed chromogranin-A. Partial loss of melanoma markers and expression of neuroendocrine markers seems not to be infrequent. In patients with a history of malignant melanoma and suspected metastases, losing melanoma markers while expressing neuroendocrine markers is a potential diagnostic pitfall. Therefore all 3 melanoma markers should be performed as well as chromogranin-A staining. In doubt, metastases of the melanoma should be assumed.
C1 [Steppert, Claus] Klinikum Bayreuth, Department of Pulmonology and Thoracic Oncology, Preuschwitzer Str. 101Bayreuth, D-95445, Germany.
[Krugmann, Jens] Klinikum Bayreuth, Department of Pathology, Preuschwitzer Str. 101Bayreuth, D-95445, Germany.
[Sterlacci, William] Klinikum Bayreuth, Department of Pathology, Preuschwitzer Str. 101Bayreuth, D-95445, Germany.
RP Steppert, C (reprint author), Klinikum Bayreuth, Department of Pulmonology and Thoracic Oncology, Bayreuth, Germany.
EM claus.steppert@klinikum-bayreuth.de
CR Shinohara MM, Deubner H, Argenyi ZB., 2009, S100, HMB-45, and Melan-A negative primary melanoma. Dermatol Online J. Sep 15;15(9):7
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Ilardi G, Caroppo D, Varricchio S, Vita G, Di Lorenzo P, Insabato L, De Rosa G,MascoloM(2015, Analmelanoma with neuroendocrine differentiation: report of a case. Int J Surg Pathol 23:329–332
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1777
EP 1779
DI 10.1007/s12253-019-00761-7
PG 3
ER
PT J
AU Rivera-Franco, MM
Leon-Rodriguez, E
Torres-Ruiz, JJ
Gomez-Martin, D
Angles-Cano, E
Sevilla-Gonzalez, dlLM
AF Rivera-Franco, M Monica
Leon-Rodriguez, Eucario
Torres-Ruiz, J Jose
Gomez-Martin, Diana
Angles-Cano, Eduardo
Sevilla-Gonzalez, de la Luz Maria
TI Neutrophil Extracellular Traps Associate with Clinical Stages in Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Neutrophil extracellular traps; Breast Cancer; Metastasis
ID Neutrophil extracellular traps; Breast Cancer; Metastasis
AB Recently, neutrophil extracellular traps (NETs), three-dimensional structures formed of neutrophil enzymes such as neutrophil elastase (NE) and nuclear components (DNA), have been associated with progression in different types of cancer. However, data remain scarce in breast cancer. Thus, the aim of this study was to associate NETs with clinical stages of breast cancer. A prospective analysis was performed in 45 plasma samples of female patients with newly diagnosed breast cancer. NE-DNA complexes were evaluated by ELISA. Optical density was dichotomized at the median for comparisons (low and high levels of NE-DNA). The most frequent clinical stage was localized (n = 28, 62%) followed by regional (n = 13, 29%) and distant (n = 4, 9%). Higher levels of NE-DNA complexes were observed in regional and distant stages compared to localized disease (68% vs 32%, p = 0.034). No differences were observed when comparing other clinical characteristics between both groups. We demonstrated that the levels of NETs increase in proportion to the stage of the disease, observing higher levels of NE-DNA complexes in regional and metastatic disease, which coincides with the proposed mechanism by which cancer progression and metastasis might result from the formation of NETs.
C1 [Rivera-Franco, M Monica] Instituto Politecnico Nacional, Escuela Superior de Medicina, Section of Graduate and Research Studies, Plan de San Luis y Diaz Miron s/n, Casco de Santo Tomas, Miguel Hidalgo, 11340 Mexico City, Mexico.
[Leon-Rodriguez, Eucario] Department of Hematology and OncologyMexico City, Mexico.
[Torres-Ruiz, J Jose] Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Department of Hematology and Oncology, Vasco de Quiroga 15, Belisario Dominguez Seccion XVI, Tlalpan, 14080 Mexico City, Mexico.
[Gomez-Martin, Diana] Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Ave. Morones Prieto 3000, 64710 Nuevo Leon, Mexico.
[Angles-Cano, Eduardo] Faculte de Pharmacie de Paris, Inserm UMR_S1140 Innovative Therapies in Haemostasis, 4 Avenue de l’Observatoire, 75006 Paris, France.
[Sevilla-Gonzalez, de la Luz Maria] Instituto Politecnico Nacional, Escuela Superior de Medicina, Section of Graduate and Research Studies, Plan de San Luis y Diaz Miron s/n, Casco de Santo Tomas, Miguel Hidalgo, 11340 Mexico City, Mexico.
RP Rivera-Franco, MM (reprint author), Instituto Politecnico Nacional, Escuela Superior de Medicina, Section of Graduate and Research Studies, 11340 Mexico City, Mexico.
EM mm.riverafranco@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1781
EP 1785
DI 10.1007/s12253-019-00763-5
PG 5
ER
PT J
AU Mohamed, EZAF
El, ZIK
Toni, DMN
AF Mohamed, El-Zahraa Ammar Fatma
El, Zahraa Ibrahim Khalil
Toni, D M Nisreen
TI Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveolin-1; Vascular endothelial growth factor; Osteosarcoma; Immunohistochemistry
ID Caveolin-1; Vascular endothelial growth factor; Osteosarcoma; Immunohistochemistry
AB Caveolin-1, the major protein component of caveolae, plays vital functions in tumorigenesis and metastasis. Previous evidence demonstrated the positive role of Caveolin-1 in the regulation of endothelial cell differentiation and the involvement of Caveolin- 1 in vascular endothelial growth factor (VEGF) mediated angiogenesis. The correlation of Caveolin-1 expression and angiogenesis is not yet elucidated in osteosarcoma. This study aimed to investigate the expression levels of Caveolin-1 and VEGF in osteosarcoma and their associations with clinicopathological data. This study included 66 formalin-fixed and paraffin embedded osteosarcoma tissue samples. The expression levels of Caveolin-1 and VEGF were assessed by immunohistochemistry. Then associations with clinicopathological variables and the correlation between both markers were evaluated statistically. We also investigated the expression of Caveolin-1 and VEGF values in gene microarrays of osteosarcoma patients and cell lines by using GEO data sets on https://www.ncbi.nlm.nih.gov. Caveolin-1 and VEGF were expressed in 19.6% and 77.3%, respectively. Caveolin-1 expression was associated positively with osteoblastic histological subtype (P < 0.0001). VEGF expression showed positive association with patient age, histological grade and clinical stage (P = 0.031, P = 0.024 and P < 0.001; respectively).An inverse correlation between Caveolin-1 and VEGF expressions in osteosarcoma was found (r = 0.2 P = 0.04). In silico analysis of Caveolin-1 and VEGF expression supported our results. Our results suggest that Caveolin-1 may act as a tumor suppressor in osteosarcoma. Down-regulation of Caveolin-1 can be used as an indicator for poor prognosis in osteosarcoma patients. Meanwhile, overexpression of VEGF is a predictor of pulmonary metastasis and poor prognosis.
C1 [Mohamed, El-Zahraa Ammar Fatma] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
[El, Zahraa Ibrahim Khalil] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
[Toni, D M Nisreen] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
RP El, ZIK (reprint author), Minia University, Faculty of Medicine, Pathology Department, Minia, Egypt.
EM zahraa333eg@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1787
EP 1795
DI 10.1007/s12253-019-00755-5
PG 9
ER
PT J
AU Sarnyai, F
Szekerczes, T
Csala, M
Sumegi, B
Szarka, A
Schaff, Zs
Mandl, J
AF Sarnyai, Farkas
Szekerczes, Timea
Csala, Miklos
Sumegi, Balazs
Szarka, Andras
Schaff, Zsuzsa
Mandl, Jozsef
TI BGP-15 Protects Mitochondria in Acute, Acetaminophen Overdose Induced Liver Injury
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Mitochondria; Acetaminophen; Liver injury; BGP-15; Reduced glutathione; Jun-kinase
ID Mitochondria; Acetaminophen; Liver injury; BGP-15; Reduced glutathione; Jun-kinase
AB Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced liver damage. Effect of BGP-15 was further investigated on mitochondria in APAP-overdose induced acute liver injury in mice. We found that BGP-15 efficiently preserved mitochondrial morphology, and it caused a marked decrease in the number of damaged mitochondria. Attenuation of mitochondrial damage by BGP-15 is supported by immunohistochemistry as the TOMM20 label and the co-localized autophagy markers detected in the livers of APAP-treated mice were markedly reduced upon BGP-15 administration. This effect, along with the observed prevention of JNK activation likely contribute to the mitochondrial protective action of BGP-15.
C1 [Sarnyai, Farkas] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Csala, Miklos] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
[Sumegi, Balazs] University of Pecs, Institute of Biochemistry and Medical ChemistryPecs, Hungary.
[Szarka, Andras] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular BiologyBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi ut 93, H-1091 Budapest, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and PathobiochemistryBudapest, Hungary.
RP Schaff, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM schaff.zsuzsa@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1797
EP 1803
DI 10.1007/s12253-019-00721-1
PG 7
ER
PT J
AU Zengin, M
AF Zengin, Mehmet
TI Local Inflammatory Response Can Predict Clinical Outcome in Patients with Curatively Resected Stage-IIB Colon Cancer: An Advanced Methodological Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Local inflammatory response; tumour biomarkers; colon cancers; stage -IIB
ID Local inflammatory response; tumour biomarkers; colon cancers; stage -IIB
AB Purpose: Although local inflammatory response (LIR) is a reliable survival marker in colon cancers (CCs), there is no consensus on its use in daily practice. We investigated the prognostic value of LIR in a highly homogeneous population with a well-designed methodology. Methods: Eighty stage-IIB CC patients operated between 2002 and 2012 were included in the study. Standardization was investigated for extra-biopsy evaluation methods (magnification, staining, and counting). Model A was used for intra-biopsy evaluation methods (block, section, and focus). So, this study makes important contributions to the standardization of pathological evaluations. Results: In method 1, the following analyzes showed more successful results for LIR: relationship with prognostic factors [tumour deposits (p=0.017), Crohn’s-like reaction (p=0.019), advanced grade, (p=0.012), positive surgical margin (p=0.019), perineural invasion (p=0.025), mismatch repair proteins-proficiency (p=0.031)], reproducibility of the study (Kappa=0.49–0.73, Intra-class correlation=0.442–0.724), and correlation of estimates (r=0.704). The cut-off value was also quite useful (area of under ROC=0.820 [0.694-0.920]). In univariate analysis, low LIR was related to poor overall survival (OS; p<0.001) and poor relapse-free survival (RFS, p=0.001) . Multivariate analysis confirmed that low LIR is an independent poor survival marker for OS (Hazard Ratio [HR]=1.32 [1.08-1.61, p=0.005) and RFS (HR=1.50 [1.22-1.85], p<0.001). Conclusions: Our results showed that low LIR had an independent prognostic significance in stage -IIB CCs.We also recommend using model A and method 1 for successful results and standardization.
C1 [Zengin, Mehmet] Kirikkale University, Department of PathologyKirikkale, Turkey.
RP Zengin, M (reprint author), Kirikkale University, Department of Pathology, Kirikkale, Turkey.
EM mz1379@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1805
EP 1816
DI 10.1007/s12253-019-00758-2
PG 12
ER
PT J
AU Usman, M
Ilyas, A
Hashim, Z
Shamshad, Z
AF Usman, Muhammad
Ilyas, Amber
Hashim, Zehra
Shamshad, Zarina
TI Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Serum biomarkers; OSCC; GIMAP7; Rabl3; Proteomics
ID Serum biomarkers; OSCC; GIMAP7; Rabl3; Proteomics
AB Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers and has been listed as sixth most common human cancer. Due to late diagnosis and insufficient therapeutic response among patients, the survival rate remains very low accentuating the importance of early diagnostic markers. The study aimed to identify differentially expressed proteins in search for putative serum biomarkers and drug targets. Serum samples (n = 45) were depleted and resolved on two dimensional gel electrophoresis. Among differentially expressed proteins, two were identified using MALDI-TOF mass spectrometry. Gene expression levels of identified proteins were quantified in malignant and normal tissue using RT-qPCR. To validate serum Rabl3 expression, sandwich ELISA was performed. Proteomics analysis revealed two proteins which were found to be associated with oral cancer. The expression of GIMAP7 was found to be down regulated in serum of patients suffering from oral cancer while the expression of Rabl3 was found to be up-regulated. Gene expression analysis in malignant tissue and adjacent normal tissue revealed the same pattern. Quantitative ELISA was used to validate expression of Rabl3 in serum from oral cancer patients and healthy subjects which demonstrated significant up-regulation in cancer patients. Findings in current study demonstrate differential expression of novel putative biomarkers GIMAP7 and Rabl3 in oral cancer which suggests their potential role in oral cancer pathology and can be considered as predictive biomarkers.
C1 [Usman, Muhammad] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Ilyas, Amber] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Hashim, Zehra] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
[Shamshad, Zarina] University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
RP Shamshad, Z (reprint author), University of Karachi, National Center for Proteomics, 75270 Karachi, Pakistan.
EM szarina@uok.edu.pk
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1817
EP 1822
DI 10.1007/s12253-019-00775-1
PG 6
ER
PT J
AU Eldin, EM
Makboul, R
Behnsawy, MH
Abdelkawi, FI
Moeen, MA
Faddan, AA
Gadelmoula, M
Shahat, AA
Abdel-Aziz, AM
Hafez, MM
Hameed, D
AF Eldin, Emad Mohamed
Makboul, Rania
Behnsawy, M Hosny
Abdelkawi, F Islam
Moeen, M Ahmed
Faddan, Abou Amr
Gadelmoula, Mohamed
Shahat, A Ahmed
Abdel-Aziz, Atef Mohamed
Hafez, M Moemen
Hameed, A. Diaa
TI Comparative Application of Different Substaging Techniques for Non-Muscle Invasive Urothelial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Substaging; Non-muscle invasive; Urothelial carcinoma; Urinary bladder
ID Substaging; Non-muscle invasive; Urothelial carcinoma; Urinary bladder
AB To evaluate the diagnostic performance and clinical significance of 4 systems of substaging cases with non-muscle invasive urothelial bladder carcinoma. In addition 4 cutoff measures were evaluated for prediction of muscularis-mucosa invasion. Four substaging systems were applied to 57 NMIBC cases to assess which of these reported methods correlates best with recurrence and progression. On univariate regression analysis patients having tumor size more than 3 cm, solid tumor architecture, high grade, substage B, substage T1e, substage ROL 2 and Tumor depth more than 1 mm were associated with higher recurrence. On multivariate analysis all the four substaging systems, tumor size, grade and tumor type had significant prognostic value for recurrence. Regarding progression only the metric substaging method was associated with tumor progression (p = 0.04). However, on univariate and multivariate regression analysis none of the substaging systems showed prognostic significance and only solid tumor architecture and CIS had significant prognostic value for tumor progression. The ROC curve analysis showed that 1 mm depth of invasion had the best accuracy for detection of muscularis-mucosa invasion (80.2%). Using 1 mm cutoff in measuring the depth and 0.5 mm for the diameter of infiltration may provide clinically relevant information to guide a more personalized therapy for NMIBC. Inclusion of both measures in addition to other histopathologic variables may aid in the development of a scoring system.
C1 [Eldin, Emad Mohamed] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Makboul, Rania] Asyut University, Faculty of Medicine, Pathology DepartmentAssiut, Egypt.
[Behnsawy, M Hosny] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Abdelkawi, F Islam] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Moeen, M Ahmed] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Faddan, Abou Amr] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Gadelmoula, Mohamed] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Shahat, A Ahmed] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Abdel-Aziz, Atef Mohamed] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
[Hafez, M Moemen] Asyut University, Faculty of Medicine, Pathology DepartmentAssiut, Egypt.
[Hameed, A. Diaa] Assiut University, Urology and Nephrology HospitalAsyut, Egypt.
RP Abdelkawi, FI (reprint author), Assiut University, Urology and Nephrology Hospital, Asyut, Egypt.
EM islamfaa@yahoo.com
CR Ploeg M, Aben KK, Kiemeney LA, 2009, The present and future burden of urinary bladder cancer in the world. World J Urol 27(3): 289–293
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van der Aa MN, van Leenders GJ, Steyerberg EW, van Rhijn BW, Jobsis AC, Zwarthoff EC, van der Kwast TH, 2005, A new system for substaging pT1 papillary bladder cancer: a prognostic evaluation. Human Pathol 36(9):981–986
van Rhijn BW, van der Kwast TH, Alkhateeb SS, Fleshner NE, van Leenders GJ, Bostrom PJ, van der Aa MN, Kakiashvili DM, Bangma CH, Jewett MA et al, 2012, A new and highly prognostic system to discern T1 bladder cancer substage. Eur Urol 61(2):378– 384
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1823
EP 1831
DI 10.1007/s12253-019-00767-1
PG 9
ER
PT J
AU Gao, J
Ma, PX
Deng, ShF
Jiang, L
Jia, DW
Li, M
AF Gao, Jian
Ma, Peng Xiao
Deng, Sheng Fu
Jiang, Lin
Jia, Dong Wei
Li, Ming
TI Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BRAF gene; PAQR3; Thyroid cancer; Papillary thyroid microcarcinoma; Lymph node metastasis (LNM); Extrathyroidal extension
ID BRAF gene; PAQR3; Thyroid cancer; Papillary thyroid microcarcinoma; Lymph node metastasis (LNM); Extrathyroidal extension
AB The BRAFV600E mutation is the most prevalent genetic event in patients with papillary thyroid cancer (PTC). However, no study has investigated the expression of PAQR3 in papillary thyroid tissues in relation to the BRAFV600E mutation and the clinicopathological features of PTC patients. Furthermore, the potential associations of the BRAFV600E mutation, PAQR3 expression and clinicopathological parameters in the cancerous tissues of PTC patients have not been investigated. This study was conducted on 60 patients with PTC who were treated surgically at our institution from 2017 to 2018. PCR was used to amplify DNA by the amplification refractorymutation system (ARMS) method to detect BRAFV600E gene mutations. In addition, immunohistochemical techniques were utilized to assess PAQR3 expression in tumor tissue sections. The BRAFV600E mutation was associated with lymph node metastasis (LNM, p < 0.05) but not with other clinicopathological features. Low PAQR3 expression was associated with extrathyroidal extension and LNM (χ2 = 7.143, p = 0.009; χ2 = 6.459, p = 0.014, respectively). Furthermore, a statistically significant association was observed between chronic lymphocytic thyroiditis and LNM (χ2 = 5.275, p = 0.0250). A linear relationship between the BRAFV600E mutation and PAQR3 protein expression has not been identified. These factors may be independent risk factors of extrathyroidal extension and LNM in PTC and be used to indicate the invasiveness of PTC tumors. Higher quality, multivariate analyses based on larger samples from around the world are urgently needed to further validate and revise our findings in the future.
C1 [Gao, Jian] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Division of Thyroid and Breast Surgery, Department of General Surgery, 230036 Hefei, Anhui, China.
[Ma, Peng Xiao] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Division of Thyroid and Breast Surgery, Department of General Surgery, 230036 Hefei, Anhui, China.
[Deng, Sheng Fu] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Division of Thyroid and Breast Surgery, Department of General Surgery, 230036 Hefei, Anhui, China.
[Jiang, Lin] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Division of Thyroid and Breast Surgery, Department of General Surgery, 230036 Hefei, Anhui, China.
[Jia, Dong Wei] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of Hepatic Surgery, 230001 Hefei, Anhui, China.
[Li, Ming] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of Pathology, 230001 Hefei, Anhui, China.
RP Gao, J (reprint author), University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Division of Thyroid and Breast Surgery, Department of General Surgery, 230036 Hefei, China.
EM gaojianahslyy@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1833
EP 1841
DI 10.1007/s12253-019-00779-x
PG 9
ER
PT J
AU Oka, S
Ono, K
Nohgawa, M
AF Oka, Satoko
Ono, Kazuo
Nohgawa, Masaharu
TI Clinical Effect of CD25 on the Prognosis of Diffuse Large B Cell Lymphoma with Secondary Central Nervous System Relapse
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Diffuse large B cell lymphoma; Central nervous system relapse; CD25; Rituximab
ID Diffuse large B cell lymphoma; Central nervous system relapse; CD25; Rituximab
AB In the present study, we investigated the effects of immunophenotyping on prognosis of diffuse large B cell lymphoma (DLBCL) with central nervous system (CNS) relapse treated with rituximab-CHOP (R-CHOP). CNS relapse occurred in 9.5% of DLBCL patients. At the diagnosis of DLBCL, CD25 was detected in 14.3% of cases. CD25 positivity correlated with an advanced stage, higher R-IPI, higher CNS-IPI, the presence of B symptoms, the presence of extranodal involvement >1, and bone involvement. Moreover CNS relapse was more frequently observed in patients with CD25+ than in those with CD25-. The univariate analysis showed that an advanced stage, high-risk R-IPI, high-risk CNS-IPI, bone involvement, and CD25+ were associated with shorter overall survival (OS). The multivariate analysis confirmed that CD25+ and high-risk CNS-IPI were independent adverse prognostic factors for shorter OS. A Kaplan-Meier analysis revealed the potential of CD25+ as a prognostic factor in patients with CNS relapse and that it correlated with shorter survival. The present results showed that the expression of CD25 in DLBCL patients with CNS relapse was associated with the patient prognosis independent other prognostic factors. The establishment of a treatment strategy for CNS relapse patients with CD25+ DLBCL cells is needed to improve poor outcomes.
C1 [Oka, Satoko] Japanese Red Cross Society Wakayama Medical Center, Division of HematologyWakayama, Japan.
[Ono, Kazuo] Japanese Red Cross Society Wakayama Medical Center, Division of PathologyWakayama, Japan.
[Nohgawa, Masaharu] Japanese Red Cross Society Wakayama Medical Center, Division of HematologyWakayama, Japan.
RP Oka, S (reprint author), Japanese Red Cross Society Wakayama Medical Center, Division of Hematology, Wakayama, Japan.
EM okas@jasmine.ocn.ne.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1843
EP 1850
DI 10.1007/s12253-019-00778-y
PG 8
ER
PT J
AU Gao, Y
Yang, M
Wei, L
Liang, X
Wu, F
Huang, Y
Yang, T
AF Gao, Ying
Yang, Ming
Wei, Liuliu
Liang, Xiaofang
Wu, Fang
Huang, Yalan
Yang, Tao
TI miR-34a-5p Inhibits Cell Proliferation, Migration and Invasion Through Targeting JAG1/Notch1 Pathway in HPV-Infected Human Epidermal Keratinocytes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miR-34a-5p; Jagged 1 (JAG1); Notch1 pathway; Human papillomavirus (HPV); Condyloma acuminate (CA)
ID miR-34a-5p; Jagged 1 (JAG1); Notch1 pathway; Human papillomavirus (HPV); Condyloma acuminate (CA)
AB Condyloma acuminate (CA) is a communicable disease caused by human papillomavirus (HPV). This study aimed to study the targeting relationship between miR-34a-5p and Jagged 1 (JAG1), as well as its regulatory effect in HPV-infected cells. Human keratinocyte HaCaT cells were infected with HPV16E6, and CA tissues were collected. The expression level of miR-34a-5p and JAG1 were detected in CA tissues and HPV-HaCaT cells. Cell proliferation, migration and invasion were respectively measured using 3-(4, 5)-dimethylthiahiazo-(−z-y1)-3, 5-diphenytetrazoliumromide (MTT), cell wound healing and Transwell assay. The potential binding sites of miR-34a-5p and JAG1 were predicted by website TargetScan, and confirmed using dual luciferase reporter gene assay. The proteins of Notch1 pathway-related were assessed using western blotting. The results showed that miR- 34a-5p expression was decreased, and JAG1 expression was increased in CA tissues and HPV-HaCaT cells. Cell proliferation, migration and invasion were decreased when miR-34a-5p over-expression and JAG1 knock-down in HPV-HaCaT cells. Furthermore, miR-34a-5p had a targeting effect on JAG1. The expression level of Notch1, NICD, Hes1 and Hey1 were increased when miR-34a-5p knock-down.miR-34a-5p could inhibit cell development, and regulate the activity of Notch1 pathway through targeting JAG1 expression in HPV-infected keratinocytes.
C1 [Gao, Ying] Huazhong University of Science and Technology, Tongji Medical College, The Central hospital of Wuhan, Department of Dermatology, 430014 Wuhan, Hubei Province, China.
[Yang, Ming] Huazhong University of Science and Technology, Tongji Medical College, The Central hospital of Wuhan, Department of Dermatology, 430014 Wuhan, Hubei Province, China.
[Wei, Liuliu] Ganzhou People’s Hospital, Department of Gastroenterology, 341000 Ganzhou, Jiangxi Province, China.
[Liang, Xiaofang] Huazhong University of Science and Technology, Tongji Medical College, The Central hospital of Wuhan, Department of Dermatology, 430014 Wuhan, Hubei Province, China.
[Wu, Fang] Huazhong University of Science and Technology, Tongji Medical College, The Central hospital of Wuhan, Department of Dermatology, 430014 Wuhan, Hubei Province, China.
[Huang, Yalan] Huazhong University of Science and Technology, Tongji Medical College, The Central hospital of Wuhan, Department of Dermatology, 430014 Wuhan, Hubei Province, China.
[Yang, Tao] the First Affiliated Hospital of Gannan Medical University, Department of Dermatology, 341000 Ganzhou, Jiangxi Province, China.
RP Yang, T (reprint author), the First Affiliated Hospital of Gannan Medical University, Department of Dermatology, 341000 Ganzhou, China.
EM TaoYangset@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1851
EP 1859
DI 10.1007/s12253-019-00782-2
PG 9
ER
PT J
AU Kocsis, A
Karsko, L
Kurgyis, Zs
Besenyi, Zs
Pavics, L
Dosa-Racz,
Kis, E
Baltas, E
Ocsai, H
Varga, E
Bende, B
Varga, A
Mohos, G
Korom, I
Varga, J
Kemeny, L
Nemeth, BI
Olah, J
AF Kocsis, Adrienn
Karsko, L
Kurgyis, Zsuzsanna
Besenyi, Zsuzsanna
Pavics, Laszlo
Dosa-Racz, Eva
Kis, Eniko
Baltas, Eszter
Ocsai, Henriette
Varga, Erika
Bende, Balazs
Varga, Attila
Mohos, Gabor
Korom, Irma
Varga, Jozsef
Kemeny, Lajos
Nemeth, Balazs Istvan
Olah, Judit
TI Is it Necessary to Perform Sentinel Lymph Node Biopsy in Thin Melanoma? A Retrospective Single Center Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; Sentinel lymph node biopsy; Mitotic rate; Regression; Stage
ID Melanoma; Sentinel lymph node biopsy; Mitotic rate; Regression; Stage
AB Sentinel lymph node biopsy (SLNB) is a standard procedure for regional lymph node staging and still has the most important prognostic value for the outcome of patients with thin melanoma. In addition to ulceration, SLNB had to be considered even for a single mitotic figure in thin (<1mm)melanoma according to AJCC7th guideline, therefore, a retrospective review was conducted involving 403 pT1 melanoma patients. Among them, 152 patients suffered from pT1b ulcerated or mitotic rate ≥ 1/ mm2 melanomas according to the AJCC7th staging system. SLNB was performed in 78 cases, of which nine (11.5%) showed SLN positivity. From them, interestingly, we found a relatively high positive sentinel rate (6/78–8%) in the case of thin primary melanomas ˂0.8 mm. Moreover, the presence of regression increased the probability of sentinel positivity by 5.796 fold. After reassessing pT stage based on the new AJCC8th, 37 pT1b cases were reordered into pT1a category. There was no significant relation between other characteristics examined (age, gender, Breslow, Clark level, and mitosis index) and sentinel node positivity. Based on our data, we suggest that mitotic rate alone is not a sufficiently powerful predictor of SLN status in thin melanomas. If strict histopathological definition criteria are applied, regression might be an additional adverse feature that aids in identifying T1 patients most likely to be SLN-positive. After reassessing of pT1b cases according to AJCC8th regression proved to be independent prognostic factor on sentinel lymph node positivity. Our results propose that sentinel lymph node biopsy might also be considered at patients with regressive thin (˂0.8 mm) melanomas.
C1 [Kocsis, Adrienn] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Karsko, L] University of Szeged, Department of Nuclear MedicineSzeged, Hungary.
[Kurgyis, Zsuzsanna] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Besenyi, Zsuzsanna] University of Szeged, Department of Nuclear MedicineSzeged, Hungary.
[Pavics, Laszlo] University of Szeged, Department of Nuclear MedicineSzeged, Hungary.
[Dosa-Racz, Eva] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Kis, Eniko] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Baltas, Eszter] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Ocsai, Henriette] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Varga, Erika] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Bende, Balazs] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Varga, Attila] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Mohos, Gabor] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Korom, Irma] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Varga, Jozsef] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Kemeny, Lajos] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Nemeth, Balazs Istvan] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Olah, Judit] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
RP Nemeth, BI (reprint author), University of Szeged, Department of Dermatology and Allergology, Szeged, Hungary.
EM nemethistvanbalazs@gmail.com;nemeth.istvan.balazs@med.uszeged.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1861
EP 1868
DI 10.1007/s12253-019-00769-z
PG 8
ER
PT J
AU Zhang, Sh
He, J
Tang, M
Sun, H
AF Zhang, Shouru
He, Jingping
Tang, Maocai
Sun, Hao
TI Prdx2 Upregulation Promotes the Growth and Survival of Gastric Cancer Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Peroxiredoxin2; Gastric cancer; Carcinogenesis
ID Peroxiredoxin2; Gastric cancer; Carcinogenesis
AB Peroxiredoxins (Prdxs) play important roles in cell proliferation, differentiation, and the mediation of intracellular signalling pathways. Prdx2 is an important member of the peroxiredoxin family and is upregulated in many cancers. Until now, the biological functions of Prdx2 in gastric cancer have not been completely understood, and the underlying mechanisms remain elusive. The aim of this study was to identify the role of Prdx2 on the growth of gastric cancer cells and the underlying mechanisms. We demonstrated that Prdx2 was highly expressed in gastric cancer tissues and cell lines and that the overexpression of Prdx2 correlated with the progression of gastric cancer. Further, Prdx2 was silenced with a specific, lentiviral vector-mediated shRNA, and this suppressed the proliferation of gastric cancer cells and promoted the apoptosis of gastric cancer cells. Finally, the knockdown of Prdx2 contributed to the attenuated gastric cancer growth in BALB/c nude mice. In conclusion, these findings demonstrate that Prdx2 may participate in the carcinogenesis and development of gastric cancer.
C1 [Zhang, Shouru] Chongqing University, Cancer Hospital, Department of Gastrointestinal Surgery, 400030 Chongqing, China.
[He, Jingping] Chongqing University, Cancer Hospital, Department of Gastrointestinal Surgery, 400030 Chongqing, China.
[Tang, Maocai] Chongqing University, Cancer Hospital, Department of Gastrointestinal Surgery, 400030 Chongqing, China.
[Sun, Hao] Chongqing University, Cancer Hospital, Department of Gastrointestinal Surgery, 400030 Chongqing, China.
RP Sun, H (reprint author), Chongqing University, Cancer Hospital, Department of Gastrointestinal Surgery, 400030 Chongqing, China.
EM sunhao68@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1869
EP 1877
DI 10.1007/s12253-019-00783-1
PG 9
ER
PT J
AU Tripodi, APA
Randelovic, I
Biri-Kovacs, B
Szeder, B
Mezo, G
Tovari, J
AF Tripodi, Angelo Pierluigi Andrea
Randelovic, Ivan
Biri-Kovacs, Beata
Szeder, Balint
Mezo, Gabor
Tovari, Jozsef
TI In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Targeted tumor therapy; NGR peptides; Tumor growth inhibition; Antiangiogenic effect; CD13; Metastasis
ID Targeted tumor therapy; NGR peptides; Tumor growth inhibition; Antiangiogenic effect; CD13; Metastasis
AB Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi’s Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa- GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.
C1 [Tripodi, Angelo Pierluigi Andrea] Eotvos Lorand University, Hungarian Academy of Sciences, MTA-ELTE Research Group of Peptide ChemistryBudapest, Hungary.
[Randelovic, Ivan] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Biri-Kovacs, Beata] Eotvos Lorand University, Hungarian Academy of Sciences, MTA-ELTE Research Group of Peptide ChemistryBudapest, Hungary.
[Szeder, Balint] Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of EnzymologyBudapest, Hungary.
[Mezo, Gabor] Eotvos Lorand University, Hungarian Academy of Sciences, MTA-ELTE Research Group of Peptide ChemistryBudapest, Hungary.
[Tovari, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
RP Tovari, J (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Budapest, Hungary.
EM tozsi@oncol.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1879
EP 1892
DI 10.1007/s12253-019-00773-3
PG 14
ER
PT J
AU Sun, L
Wang, Y
Shi, J
Zhu, W
Wang, X
AF Sun, Le
Wang, Yusheng
Shi, Jinfeng
Zhu, Wei
Wang, Xin
TI Association of Plasma Epstein-Barr Virus LMP1 and EBER1 with Circulating Tumor Cells and the Metastasis of Nasopharyngeal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epstein-Barr virus; LMP1; BART; EBER1; Metastasis; Nasopharyngeal carcinoma
ID Epstein-Barr virus; LMP1; BART; EBER1; Metastasis; Nasopharyngeal carcinoma
AB Epstein-Barr virus (EBV) has been widely recognized to contribute to the development of nasopharyngeal carcinoma (NPC). The present study was to explore the association of plasma Epstein-Barr Virus LMP1 and EBER1 with circulating tumor cells (CTCs) and the metastasis of nasopharyngeal carcinoma. In the present study, we quantified the plasma levels of EBV DNA/RNAs, such as LMP1, LMP2, BART and EBER1 with real-time quantitative PCR, and CTCs with a CellSpotter Analyzer in NPC patients, with or without metastasis. Then the correlation of each biomarker with other biomarkers and tumor metastasis was analyzed. Our data indicated that the plasma levels of EBV LMP1, BART, EBER1, along with CTCs were significantly higher in metastatic NPC patients than in non-metastatic patients. Plasma LMP1 DNA and EBER1 discriminate metastatic NPC patients from nonmetastatic patients, correlate with tumor stage and node stage for metastatic NPC patients. In summary, there were significantly higher plasma levels of Epstein-Barr Virus DNAs / RNAs in nasopharyngeal carcinoma patients. LMP1 DNA and EBER1 RNA correlated with the metastasis of nasopharyngeal carcinoma.
C1 [Sun, Le] First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 71#, Xinmin Street, 130021 Changchun, China.
[Wang, Yusheng] First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 71#, Xinmin Street, 130021 Changchun, China.
[Shi, Jinfeng] First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 71#, Xinmin Street, 130021 Changchun, China.
[Zhu, Wei] First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 71#, Xinmin Street, 130021 Changchun, China.
[Wang, Xin] First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 71#, Xinmin Street, 130021 Changchun, China.
RP Sun, L (reprint author), First Hospital of Jilin University, Department of Otolaryngology, Head & Neck Surgery, 130021 Changchun, China.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1893
EP 1901
DI 10.1007/s12253-019-00777-z
PG 9
ER
PT J
AU Yu, Ch
Chen, J
Ma, J
Zang, L
Dong, F
Sun, J
Zheng, M
AF Yu, Chaoran
Chen, Jie
Ma, Junjun
Zang, Lu
Dong, Feng
Sun, Jing
Zheng, Minhua
TI Identification of Key Genes and Signaling Pathways Associated with the Progression of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Differentially expressed genes; Gene ontology; KEGG pathway; Protein-protein interaction network; Gastric cancer; Gene set enrichment analysis
ID Differentially expressed genes; Gene ontology; KEGG pathway; Protein-protein interaction network; Gastric cancer; Gene set enrichment analysis
AB Genomic features have been gradually regarded as part of the fundamentals to the clinical diagnosis and treatment for gastric cancer. However, the molecular alterations taking place during the progression of gastric cancer remain unclear. Therefore, identification of potential key genes and pathways in the gastric cancer progression is crucial to clinical practices. The gene expression profile, GSE103236, was retrieved for the identification of the differentially expressed genes (DEGs), followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments, gene set enrichment analysis (GSEA) and the protein-protein interaction (PPI) networks. Multiple bioinformatics platforms were employed for expression and prognostic analysis. Fresh frozen gastric cancer tissues were used for external validation. A total of 161 DEGs were identified from GSE103236. The PPI network-derived hub genes included collagen type I alpha 1 chain (COL1A1), tissue inhibitor of the metalloproteinases (TIMP1), Secreted Phosphoprotein 1 (SPP1), somatostatin (SST), neuropeptide Y (NPY), biglycan (BGN), matrix metallopeptidase 3 (MMP3), apolipoprotein E (APOE), ATPase H+/K+ transporting alpha subunit (ATP4A), lysyl oxidase (LOX). SPP1 (log rank p = 0.0048, HR = 1.39 [1.1–1.75]) and MMP3 (log rank p < 0.0001, HR = 1.77 [1.44–2.19]) were significantly associated with poor overall survival. Stage-specifically, both COL1A1 and BGN were correlated with significant in stage III and IV gastric cancer cases. LOX showed significant correlation with prognosis in stage I and stage II gastric cancer cases. Furthermore, cg00583003 of SPP1 and cg16466334 of MMP3 exhibited highly methylation level and significant prognostic values (SPP1: HR = 1.625, p = 0.013; MMP3: HR = 0.647, p = 0.011). Hub genes signature displayed a favorable prognostic value (p value = 5.227e-05). APOE demonstrated the highest correlation with CD8+ T cells, neutrophils, and dendritic cells whereas BGN had the highest correlation with macrophages. This study systematically explored the key genes and pathways involved in PGC and AGC, providing insights into therapeutic individualized management.
C1 [Yu, Chaoran] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Chen, Jie] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Ma, Junjun] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Zang, Lu] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Dong, Feng] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Sun, Jing] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
[Zheng, Minhua] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
RP Yu, Ch (reprint author), Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Gastrointestinal Surgery, 200025 Shanghai, China.
EM chaoran_yu@sjtu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1903
EP 1919
DI 10.1007/s12253-019-00781-3
PG 17
ER
PT J
AU Jahangiri, R
Mosaffa, F
EmamiRazavi, A
Gharib, M
Jamialahmadi, K
AF Jahangiri, Rosa
Mosaffa, Fatemeh
EmamiRazavi, Amirnader
Gharib, Masoumeh
Jamialahmadi, Khadijeh
TI Increased Expression of Gankyrin and Stemness Factor Oct-4 are Associated with Unfavorable Clinical Outcomes and Poor Benefit of Tamoxifen in Breast Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast Cancer; Tamoxifen Resistance; Gankyrin; Oct-4
ID Breast Cancer; Tamoxifen Resistance; Gankyrin; Oct-4
AB Tamoxifen is the most important treatment component in estrogen receptor positive (ER+) breast carcinoma patients. Tamoxifen resistance incidence presents an important obstacle in clinical treatment. Mechanisms underlying tamoxifen refractory are not completely understood. Although elevated expression of Gankyrin (P28GANK) and stem cell markers Nanog, Oct-4 and Sox-2 have been reported in breast carcinoma, their role in tamoxifen resistance progression has not been explored. In the present study, P28GANK and stem cell markers Nanog, Oct-4 and Sox-2 expression were evaluated using quantitative RT-PCR and immunohistochemical technology in 72 breast carcinoma patients who received tamoxifen as adjuvant anti-hormone treatment. Expression data were correlated with the clinical outcome and survival of patients. Data analysis showed that P28GANK, Oct-4 and Sox-2 transcripts were significantly overexpressed in tamoxifen resistance patients. Immunohistochemical staining indicated that protein expression of P28GANK and Oct-4 were also significantly higher in tamoxifen resistance patients. We have shown a positive correlation between mRNA and protein expression of P28GANK, Oct-4 and Sox-2. Multivariate logistic regression analysis indicated that P28GANK (P = 0.002) and Oct-4 (P = 0.013) overexpression could be negative independent factors of disease outcome. Additionally, in the whole study group, multivariate Cox regression analysis revealed that high expression of P28GANK and Oct-4 remained significant and unfavorable predictive factors for patients’ survival. These findings suggest that Gankyrin and Oct-4 overexpression could promote tamoxifen refractory in breast cancer patients. More studies are warranted to clarify the predictive role of these potential biomarkers for patients who don’t benefit from tamoxifen treatment and their possible application as prognostic markers in ER+ tamoxifen-treated breast carcinoma patients.
C1 [Jahangiri, Rosa] Mashhad University of Medical Sciences, School of Medicine, Department of Medical Biotechnology and NanotechnologyMashhad, Iran.
[Mosaffa, Fatemeh] Mashhad University of Medical Sciences, Pharmaceutical Technology Institute, Biotechnology Research CenterMashhad, Iran.
[EmamiRazavi, Amirnader] Tehran University of Medical Sciences, Cancer Institute of IranTehran, Iran.
[Gharib, Masoumeh] Mashhad University of Medical Sciences, Faculty of Medicine, Department of PathologyMashhad, Iran.
[Jamialahmadi, Khadijeh] Mashhad University of Medical Sciences, Pharmaceutical Technology Institute, Biotechnology Research CenterMashhad, Iran.
RP Jamialahmadi, K (reprint author), Mashhad University of Medical Sciences, Pharmaceutical Technology Institute, Biotechnology Research Center, Mashhad, Iran.
EM jamialahmadikh@mums.ac.ir
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1921
EP 1934
DI 10.1007/s12253-019-00766-2
PG 14
ER
PT J
AU Dong, R
Liu, J
Sun, W
Ping, W
AF Dong, Ruolan
Liu, Jiawei
Sun, Wei
Ping, Wei
TI Comprehensive Analysis of Aberrantly Expressed Profiles of lncRNAs and miRNAs with Associated ceRNA Network in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma (LUAD); Lung squamous cell carcinoma (LUSC); lncRNA; ceRNA; miRNA
ID Lung adenocarcinoma (LUAD); Lung squamous cell carcinoma (LUSC); lncRNA; ceRNA; miRNA
AB Lung cancer (LC) continues to be the leading cause of cancer-related deaths worldwide and the prognosis remains poor worldwide. At present, the long non-coding RNAs (lncRNAs) was considered as a part of competing endogenous RNA (ceRNA) network act as natural microRNA (miRNA) sponges to regulate protein-coding gene expression. However, functional roles of lncRNA-mediated ceRNAs in LC are insufficiently understood. To classify the specific mechanism of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), we comprehensively compared the expression profiles of mRNAs, lncRNAs and miRNAs obtained from 509 LUAD, 473 LUSC tissues and 49 adjacent non-cancerous lung tissues, based on The Cancer Genome Atlas (TCGA). After screening for differently expressed (DE) mRNAs,DEmiRNAs, DElncRNAs and weighted gene co-expression network analysis (WGCNA) (|log2FC| > 2.0 and an adjusted p value <0.05), a total of 4478 DEmRNAs, 526 DElncRNAs and 75 DEmiRNAs in LUAD, while 6237 DEmRNAs, 843 DElncRNAs and 117 DEmiRNAs in LUSC were discovered. Interaction (PPI) network analysis was performed to identify 656 nodes and 2987 edges (minimum required interaction score > 0.9), as well as 8 different protein-protein interactions. Gene ontology (GO) analysis mainly associated with cell proliferation. KEGG pathway enrichment analyses most partly associated with metabolism pathway and cytokine-cytokine receptor interaction. Finally, the dysregulated lncRNA-miRNA-ceRNA network was constructed based on correlation analyses and a total of 62 dysregulated lncRNAs, 28 DEmRNAs and 18 DEmiRNAs were involved. The most significant lncRNAs included DElncRNAs, LINC00641 and AC004947.2, miRNAs included miR-6860, miR-1285-3p, miR-767-3p and miR-7974, mRNAs included MAP3K3, FGD3 and ATP1B2. Then we analyzed and described the potential characteristics of biological function and pathological roles of the LUAD and LUSC ceRNA co-regulatory network. Our findings revealed ceRNA network will be beneficial for promoting the understanding of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of LUAD and LUSC.
C1 [Dong, Ruolan] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Institute of Integrated Traditional Chinese and Western Medicine, 430030 Wuhan, Hubei, China.
[Liu, Jiawei] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thoracic Surgery, 430030 Wuhan, Hubei, China.
[Sun, Wei] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thoracic Surgery, 430030 Wuhan, Hubei, China.
[Ping, Wei] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thoracic Surgery, 430030 Wuhan, Hubei, China.
RP Ping, W (reprint author), Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thoracic Surgery, 430030 Wuhan, China.
EM 247046170@qq.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1935
EP 1945
DI 10.1007/s12253-019-00780-4
PG 11
ER
PT J
AU El-Ashmawy, EN
Khedr, GE
El-Bahrawy, AH
Helmy, NN
AF El-Ashmawy, E Nahla
Khedr, G Eman
El-Bahrawy, A Hoda
Helmy, N Nada
TI Modulatory Effect of Silymarin on Apoptosis in Testosterone -Induced Benign Prostatic Hyperplasia in Rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Silymarin; Benign prostatic hyperplasia; Survivin; Bax; Bcl-2; p27/kip1
ID Silymarin; Benign prostatic hyperplasia; Survivin; Bax; Bcl-2; p27/kip1
AB Benign prostatic hyperplasia (BPH) is considered a normal part of the aging process in men, and is characterized by an imbalance between cell proliferation and apoptosis. Our study aimed to investigate the potential protective role of silymarin (SIL) against testosterone-induced BPH in rats and to elucidate the molecular mechanisms underlying SIL pro-apoptotic and anti-proliferative effects. Forty adult male Wistar rats were divided equally into four groups: control group, BPH group (3 mg/kg testosterone propionate, s.c. for 14 days, SIL group (50 mg/kg SIL, orally, once daily concomitantly with 3mg/kg testosterone propionate s.c.) and inhibitor group (50 mg/kg SIL orally concomitantly with 3 mg/kg testosterone, s.c. and 0.5 mg/rat Z-VAD-FMK, i.p.). Silymarin induced caspase-dependent apoptosis in BPH as SIL significantly reduced prostatic Bcl-2 protein and increased Bax protein concentration. Also, SIL down-regulated survivin (Inhibitor of apoptosis protein (IAPs) gene expression in rat prostate assisting mainly caspase-dependent pathway. Silymarin significantly decreased cytochrome-c cytosolic concentration and increased caspase 3 activity compared to BPH group. Silymarin significantly increased the content of p27/kip1 (Cyclin dependent kinase inhibitor (CDKIs) promoting cell cycle arrest. The histological features of BPH such as hypertrophy, papillary projections formation, improved in SIL group. Silymarin showed a significant anti-proliferative and pro-apoptotic role in BPH and accordingly it could be effectively and safely used as a treatment tool in cases of BPH or prostatic disorders.
C1 [El-Ashmawy, E Nahla] Tanta University, Faculty of Pharmacy, Department of Biochemistry, 31527 Tanta, El-Gharbia, Egypt.
[Khedr, G Eman] Tanta University, Faculty of Pharmacy, Department of Biochemistry, 31527 Tanta, El-Gharbia, Egypt.
[El-Bahrawy, A Hoda] Tanta University, Faculty of Pharmacy, Department of Biochemistry, 31527 Tanta, El-Gharbia, Egypt.
[Helmy, N Nada] Tanta University, Faculty of Pharmacy, Department of Biochemistry, 31527 Tanta, El-Gharbia, Egypt.
RP Helmy, NN (reprint author), Tanta University, Faculty of Pharmacy, Department of Biochemistry, 31527 Tanta, Egypt.
EM nada.helmi@pharm.tanta.edu.eg
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1947
EP 1956
DI 10.1007/s12253-019-00764-4
PG 10
ER
PT J
AU Baranyi, M
Rittler, D
Molnar, E
Shirasawa, S
Jalsovszky, I
Varga, KI
Hegedus, L
Nemeth, A
Dank, M
Aigner, C
Tovari, J
Timar, J
Hegedus, B
Garay, T
AF Baranyi, Marcell
Rittler, Dominika
Molnar, Eszter
Shirasawa, Senji
Jalsovszky, Istvan
Varga, Karoly Imre
Hegedus, Luca
Nemeth, Afrodite
Dank, Magdolna
Aigner, Clemens
Tovari, Jozsef
Timar, Jozsef
Hegedus, Balazs
Garay, Tamas
TI Next Generation Lipophilic Bisphosphonate Shows Antitumor Effect in Colorectal Cancer In Vitro and In Vivo
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lipophilic bisphosphonate; Zoledronic acid; Colorectal cancer; In vitro; In vivo
ID Lipophilic bisphosphonate; Zoledronic acid; Colorectal cancer; In vitro; In vivo
AB Bisphosphonates, despite proven antitumor effect in vitro in many tumor types, are currently used only for treatment of osteoporosis and bone metastasis. Colorectal cancer is the third most commonly diagnosed type of cancer and lacks targeted therapy for RAS or RAF mutation carrying cases. A new lipophilic bisphosphonate showed promising results in lung cancer models, but their effect on colorectal cancer cells was not investigated excessively. Antitumor effects and impact on RAS-related signalization of zoledronic acid (ZA) and a lipophilic bisphosphonate (BPH1222) were investigated on 7 human colorectal cancer cell lines in vitro and in vivo. Furthermore, mutant KRAS dependent effect of prenylation inhibition was investigated using isogeneic cell lines. Both bisphosphonates reduced cell viability in vitro in a dose-dependent manner. Both compounds changed cell cycle distribution similarly by increasing the proportion of cells either in the S or in the subG1 phase or both. However, BPH1222 exerted higher inhibitory effect on spheroid growth than ZA. Interestingly, we found profound alterations in phosphorylation level of Erk and S6 proteins upon ZA or BPH1222 treatment. Furthermore, investigation of a mutant KRAS isogeneic model system suggests that the drugs interfere also with the mutant KRAS proteins. In vivo experiments with KRAS mutant xenograft model also revealed growth inhibitory potential of bisphosphonate treatment. Our results show that lipophilic bisphosphonates might extend the therapeutic spectrum of bisphosphonate drugs and could be considered as additional treatment approaches in colorectal cancer.
C1 [Baranyi, Marcell] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
[Rittler, Dominika] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
[Molnar, Eszter] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
[Shirasawa, Senji] Fukuoka University, Faculty of Medicine, Department of Cell BiologyFukuoka, Japan.
[Jalsovszky, Istvan] Eotvos Lorand University, Faculty of Science, Institute of Chemistry, Department of Organic Chemistry, H-1117 Budapest, Hungary.
[Varga, Karoly Imre] Eotvos Lorand University, Faculty of Science, Institute of Chemistry, Department of Organic Chemistry, H-1117 Budapest, Hungary.
[Hegedus, Luca] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic Surgery, D-45239 Essen, Germany.
[Nemeth, Afrodite] Semmelweis University, Department of Oncology, H-1091 Budapest, Hungary.
[Dank, Magdolna] Semmelweis University, Department of Oncology, H-1091 Budapest, Hungary.
[Aigner, Clemens] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic Surgery, D-45239 Essen, Germany.
[Tovari, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, H-1122 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
[Hegedus, Balazs] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
[Garay, Tamas] Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
RP Hegedus, B (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM balazs.hegedues@rlk.uk-essen.de
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1957
EP 1969
DI 10.1007/s12253-019-00789-9
PG 13
ER
PT J
AU Rojas, EEI
Segura-Azuara, dlN
Cabrera, VLM
AF Rojas, Elisa Erana Irma
Segura-Azuara, de los Angeles Nancy
Cabrera, Vanessa Lopez Mildred
TI Breaking the Curse: Opening Students’ Eyes to Pathology and Oncology Research
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Educational innovation; Educational strategy; Academic medicine; Research
ID Educational innovation; Educational strategy; Academic medicine; Research
AB Research is a particularly underexplored professional activity for physicians, leaving many medical students compelled to pursue a clinical career. However, the XXI century requires that physicians innovate and perform research that fuels their practice; students should have early exposure to research to explore it as a career path. It should be encouraged in the undergraduate program by having students take part in case reports, short communication presentations, and research seminars. As part of an educational strategy, students worked with faculty members to deliver a gynecologic oncology pathology case report as a poster for the Oncology Conference of Medical Students. We used a quantitative approach with a descriptive and cross-sectional design to assess the effect of poster presentations on developing student’s research skills. The sample comprised 118 medical students enrolled in the Pathology courses that presented a total of 23 posters. The judges who assessed had a medical specialty in Pathology, Radio-oncology, and Gynecologic Oncology. The results show that students exceeded expectations on the use of language, as it was both formal and technical; and they used relevant bibliographic support and references. However, students performed less well in the clinical case summary. The judges found that although it was coherent and chronologically ordered, they did not include all the relevant laboratory tests and analyses, nor a full description of the diagnosis. This educational strategy has proven to be valuable in promoting Pathology and Oncology Research in students; it allowed participants to adopt a systematic approach and methodologies to document, analyze, and share knowledge.
C1 [Rojas, Elisa Erana Irma] Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Ave. Morones Prierto 3000 Pte col. Los Doctores, 64710 Monterrey, Mexico.
[Segura-Azuara, de los Angeles Nancy] Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Ave. Morones Prierto 3000 Pte col. Los Doctores, 64710 Monterrey, Mexico.
[Cabrera, Vanessa Lopez Mildred] Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Ave. Morones Prierto 3000 Pte col. Los Doctores, 64710 Monterrey, Mexico.
RP Cabrera, VLM (reprint author), Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, 64710 Monterrey, Mexico.
EM mildredlopez@tec.mx
CR Aguilar-Vargas E, Aviles-Ibarra OJ, Mendez N, 2017, Elaboracion de un articulo de reporte de caso clinico o de revision, en la materia demetodologia de la investigacion enmedicina. An Fac Med 78(1): 55–59. , DOI 10.15381/anales.v78i1.13022
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1971
EP 1974
DI 10.1007/s12253-019-00728-8
PG 4
ER
PT J
AU Malgulwar, BP
Nambirajan, A
Singh, M
Suri, V
Sarkar, Ch
Sharma, ChM
AF Malgulwar, Benny Prit
Nambirajan, Aruna
Singh, Manmohan
Suri, Vaishali
Sarkar, Chitra
Sharma, Chand Mehar
TI Expression and Clinical Significance of Translation Regulatory Long Non-Coding RNA 1 (TRERNA1) in Ependymomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ependymoma; TRERNA1; lncRNA; Epithelial to mesenchymal transition
ID Ependymoma; TRERNA1; lncRNA; Epithelial to mesenchymal transition
AB Long noncoding RNAs (lncRNA) have emerged as vital molecules governing epithelial-to-mesenchymal transition (EMT) in cancers. Translation regulatory RNA 1 (TRERNA1) is one such lncRNA known to enhance the transcriptional activity of the EMT-transcription factor, Snail. We have previously demonstrated differential upregulation of EMT-transcription factors and cadherin switching across various clinico-pathologic-molecular subclasses of ependymomas (EPN). With an aim to analyze the correlation between the expression of TRERNA1 in EPNs, we performed gene expression analysis for TRERNA1 on 75 Grade II/ III EPNs and correlated with tumor site, C11orf95-RELA fusions, age, MIB-1 proliferative indices, and outcome wherever available. Upregulation of gene expression levels of TRERNA1 was seen in intracranial EPNs, with highest expression levels in pediatric posterior fossa EPNs. High TRERNA1 expression was found associated with higher proliferative indices (p = 0.034) and shorter progression free survival (p = 0.002). Our study, for the first time, demonstrates an association between TRERNA1 expressions and pediatric posterior fossa EPNs. Further in-vivo and in-vitro studies are required to confirm these findings and evaluate TRERNA1 as a novel biomarker and potential therapeutic target in childhood PF-EPNs.
C1 [Malgulwar, Benny Prit] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029 New Delhi, India.
[Nambirajan, Aruna] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029 New Delhi, India.
[Singh, Manmohan] All India Institute of Medical Sciences, Department of Neurosurgery, 110029 New Delhi, India.
[Suri, Vaishali] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029 New Delhi, India.
[Sarkar, Chitra] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029 New Delhi, India.
[Sharma, Chand Mehar] All India Institute of Medical Sciences, Department of Pathology, Ansari Nagar, 110029 New Delhi, India.
RP Sharma, ChM (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM sharmamehar@yahoo.co.in
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1975
EP 1981
DI 10.1007/s12253-019-00736-8
PG 7
ER
PT J
AU Son, JH
An, HCh
Yoo, JN
Lee, HS
AF Son, Ji Hyun
An, Hyeok Chang
Yoo, Jin Nam
Lee, Hyung Sug
TI Tight Junction-Related CLDN5 and CLDN6 Genes, and Gap Junction-Related GJB6 and GJB7 Genes Are Somatically Mutated in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CLDN5; CLDN6; GJB6; GJB7; Mutation; Cancer
ID CLDN5; CLDN6; GJB6; GJB7; Mutation; Cancer
AB Tight junction and gap junction are major cell junctions that play important roles in cellular communication and structural integrity. Alterations of these junctions are known to be involved in cancer pathogenesis. Claudins and connexins are major tight and gap junction proteins, but genetic alterations of these genes have not been reported in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). Claudin genes CLDN5 and CKDN6, and connexin genes GJB6 and GJB7 have mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with MSI. We analyzed 79 GCs and 145 CRCs, and found CLDN5 frameshift mutations in 3 (3%) CRCs and 1 (2.9%) GC, CLDN6 frameshift mutations in 6 (6%)CRCs, GJB6 frameshift mutations in 5 (5%) CRCs and GJB7 frameshift mutation in one CRC (1%) with high MSI (MSIH). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutations in 16 CRCs and found that CLDN6 and GJB6 frameshift mutations showed regional ITH in 2 (12.5%) and 2 (12.5%) cases, respectively. Our results show that CLDN5, CLDN6, GJB6 and GJB7 genes harbor not only frameshift mutations but also mutational ITH, which together may be features of GC and CRC with MSI-H. Based on the roles of cellular junctions in cancers, frameshift mutations of tight junction and gap junction genes might contribute to tumorigenesis by altering their functions in GC and CRC.
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[An, Hyeok Chang] The Catholic University of Korea, College of Medicine, Department of General SurgerySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1983
EP 1987
DI 10.1007/s12253-020-00806-2
PG 5
ER
PT J
AU Handra-Luca, A
AF Handra-Luca, Adriana
TI Nuclear Cytoplasmic Inclusions in Lung Adenocarcinoma: Relevance of Immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Handra-Luca, Adriana] Universite Paris Nord Sorbonne Cite, APHP GHU Avicenne, Service d’Anatomie Pathologique, 125 rue Stalingrad, 93009 Bobigny, France.
RP Handra-Luca, A (reprint author), Universite Paris Nord Sorbonne Cite, APHP GHU Avicenne, Service d’Anatomie Pathologique, 93009 Bobigny, France.
EM adriana.handra-luca@aphp.fr;adriana.handra-luca@hotmail.com;adriana.handra-luca@univ-paris13.fr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1989
EP 1990
DI 10.1007/s12253-019-00714-0
PG 2
ER
PT J
AU Wang, B
Tao, L
Huang, Y
AF Wang, Bolin
Tao, Lin
Huang, Yan
TI Comment on “The Significance of Long Non-coding RNA HULC in Predicting Prognosis and Metastasis of Cancers: a Meta-Analysis”
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Wang, Bolin] Weifang School of MedicineWeifang, Shandong, China.
[Tao, Lin] Weifang School of MedicineWeifang, Shandong, China.
[Huang, Yan] Affiliated Hospital of Weifang Medical University, Department of OncologyWeifang, Shandong, China.
RP Huang, Y (reprint author), Affiliated Hospital of Weifang Medical University, Department of Oncology, Weifang, China.
EM Yanhuangdr@163.com
CR Ding Y, Sun C, Li J, Hu L, Li M, Liu J, Pu L, Xiong S, 2019, The significance of long non-coding RNA HULC in predicting prognosis and metastasis of cancers: a meta-analysis. Pathol Oncol Res 25: 311–318
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1991
EP 1992
DI 10.1007/s12253-019-00717-x
PG 2
ER
PT J
AU Oka, S
Ono, K
Nohgawa, M
AF Oka, Satoko
Ono, Kazuo
Nohgawa, Masaharu
TI Successful Retreatment with Elotuzumab for Multiple Myeloma with Extramedullary Relapse while Being Treated with Lenalidomide and Dexamethasone
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Oka, Satoko] Japanese Red Cross Society Wakayama Medical Center, Division of HematologyWakayama, Japan.
[Ono, Kazuo] Japanese Red Cross Society Wakayama Medical Center, Division of PathologyWakayama, Japan.
[Nohgawa, Masaharu] Japanese Red Cross Society Wakayama Medical Center, Division of HematologyWakayama, Japan.
RP Oka, S (reprint author), Japanese Red Cross Society Wakayama Medical Center, Division of Hematology, Wakayama, Japan.
EM okas@jasmine.ocn.ne.jp
CR Blade J, CibeiraMT, Rosinol L, de Larrea CF, 2009, Extramedullary Myeloma Blood 114:SCI–SC5
Descamps G, Pellat-Deceunynck C, Szpak Y, Bataille R, Robillard N, Amiot M, 2004, The magnitude of Akt/ phosphatidylinositol 3'-kinase proliferating signaling is related to CD45 expression in human myeloma cells. J Immunol 173: 4953–4959
Guo H, Cruz-Munoz ME, Wu N, Robbins M, Veillette A, 2015, Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells. Mol Cell Biol 35:41–51
Kumar SK, Callander NS, Alsina M, et al, 2018, NCCN Guidelines Insights; Multiple Myeloma, Version 3.2018. J Natl Compr Canc Netw 16:11–20
DimopoulosMA, Oriol A, Nahi H, San-Miguel J, BahlisNJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O’Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P, 2016, Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 375:1319– 1331
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1993
EP 1995
DI 10.1007/s12253-019-00725-x
PG 3
ER
PT J
AU Hu, HL
Zeng, DD
Zang, JL
Chen, Z
AF Hu, Hao-Liang
Zeng, Dan-Dan
Zang, Jing-Lei
Chen, Zhe
TI The Pan-Cancer Atlas: a New Chapter in Cancer Molecular Targeting Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Hu, Hao-Liang] Hunan Normal University, College of Life Sciences, 410006 Changsha, China.
[Zeng, Dan-Dan] Hunan Normal University, College of Life Sciences, 410006 Changsha, China.
[Zang, Jing-Lei] Hunan Normal University, College of Life Sciences, 410006 Changsha, China.
[Chen, Zhe] Hunan Institute of Traffic Engineering, Nursing College, 421001 Hengyang, China.
RP Zang, JL (reprint author), Hunan Normal University, College of Life Sciences, 410006 Changsha, China.
EM jlzang@126.com
CR Sticz T, Molnar A, Danko T et al, 2018, The effects of different mTOR inhibitors in EGFR inhibitor resistant Colon carcinoma cells. Pathol. Oncol. Res: POR. , DOI 10.1007/s12253- 018-0434-4
Evans M, O'Sullivan B, Hughes F et al, 2018, The Clinicopathological and molecular associations of PD-L1 expression in non-small cell lung Cancer: analysis of a series of 10,005 cases tested with the 22C3 assay. Pathol. Oncol. Res: POR. https:// doi.org/10.1007/s12253-018-0469-6
Cancer Genome Atlas Research N, Analysis Working Group, Genome Sequencing Center et al, 2017, Integrated genomic characterization of oesophageal carcinoma. Nature 541(7636):169– 175. , DOI 10.1038/nature20805
Hoadley KA, Yau C, Hinoue T et al, 2018, Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of Cancer. Cell 173(2):291–304 e296. , DOI 10. 1016/j.cell.2018.03.022
Ding L, Bailey MH, Porta-Pardo E et al, 2018, Perspective on oncogenic processes at the end of the beginning of Cancer genomics. Cell 173(2):305–320 e310. , DOI 10.1016/j.cell. 2018.03.033
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Huang KL, Mashl RJ, Wu Y et al, 2018, Pathogenic germline variants in 10,389 adult cancers. Cell 173(2):355–370 e314. , DOI 10.1016/j.cell.2018.03.039
Cilloni D, Saglio G, 2012, Molecular pathways: BCR-ABL. Clinical Cancer Research : an official journal of the American Association for Cancer Research 18(4):930–937. , DOI 10.1158/1078-0432.CCR-10-1613
Gao Q, Liang WW, Foltz SM et al, 2018, Driver fusions and their implications in the development and treatment of human cancers. Cell Rep 23(1):227–238 e223. , DOI 10.1016/j.celrep. 2018.03.050
Cancer Genome Atlas N, 2015, Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582. , DOI 10.1038/nature14129
Laroche-Clary A, Chaire V, Algeo MP et al, 2017, Combined targeting of MDM2 and CDK4 is synergistic in dedifferentiated liposarcomas. J Hematol Oncol 10(1):123. , DOI 10. 1186/s13045-017-0482-3
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 1997
EP 1999
DI 10.1007/s12253-019-00709-x
PG 3
ER
PT J
AU Gupta, AA
Shekatkar, M
Raj, Th
Kheur, S
AF Gupta, A Archana
Shekatkar, Madhura
Raj, A. Thirumal
Kheur, Supriya
TI Potential Role of Magnesium in Cancer Initiation and Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Gupta, A Archana] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, 411041 Pune, Maharashtra, India.
[Shekatkar, Madhura] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, 411041 Pune, Maharashtra, India.
[Raj, A. Thirumal] Sri Venkateswara Dental College and Hospital, Department of Oral Pathology and MicrobiologyChennai, India.
[Kheur, Supriya] Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, Dr. D.Y. Patil Vidyapeeth, 411041 Pune, Maharashtra, India.
RP Gupta, AA (reprint author), Dr. D. Y. Patil Dental College and Hospital, Department of Oral Pathology and Microbiology, 411041 Pune, India.
EM archanaanshumangupta@gmail.com
CR Grober U, Schmidt J, Kisters K, 2015, Magnesium in prevention and therapy. Nutrients 7(9):8199–8226
Hosthor SS, Mahesh P, Priya SM, Sharada P, Jyotsna M, Chitra S, 2014, Quantitative analysis of serum levels of trace elements in patients with oral submucous fibrosis and oral squamous cell carcinoma: a randomized cross – sectional study. J Oral MaxillfacPathol 18:46–51
Mendes PMV, Bezerra DLC, Santos LRD, Santos LDO, Melo SRDS, Morais JBS et al, 2018, Magnesium in breast Cancer: what is its influence on the progression of this disease? Biol Trace Elem Res 184(2):334–339
Bertinato J, Xiao CW, Ratnayake WM et al, 2015, Lower serum magnesium concentration is associated with diabetes, insulin resistance, and obesity in south Asian and white Canadian women but not men. Food Nutr Res 59(1):25974
Abdelgawad IA, El-Mously RH, Saber MM, Mansour OA, Shouman SA, 2015, Significance of serum levels of vitamin D and some related minerals in breast cancer patients. Int J Clin Exp Pathol 8(4):4074–4082
Anastassopoulou J, Theophanides T, 2015, Magnesium-DNA interactions and the possible relation ofmagnesiumto carcinogenesis. Irradiation and free radicals. Crit Rev Oncol Hematol 42(1):79–91
Karki K, Pande D, Negi R, Khanna S, Khanna RS, Khanna HD, 2015, Association between biomarkers of oxidative stress, trace elements, and cell proliferation index in patients with benign and malignant breast diseases. J Environ Pathol Toxicol Oncol 34(1):1– 10
Karki K, Pande D, Negi R, Khanna S, Khanna RS, Khanna HD, 2015, Correlation of serum toll like receptor 9 and trace elements with lipid peroxidation in the patients of breast diseases. J Trace Elem Med Biol 30:11–16
Castiglioni S,Maier JA, 2011, Magnesium and cancer : adangerous liason. Magnes Res 24(3):92–100
Yu E, Ahn YS, Jang SJ, KimMJ, Yoon HS, Gong G, Choi J, 2007, Overexpression of the wip1 gene abrogates the p38 MAPK/p53/ Wip1 pathway and silences p16 expression in human breast cancers. Breast Cancer Res Treat 101(3):269–278
Bagulkar BB, Chaudhary M, Gawande M, Patil S, Gadbail A, Bagulkar S, 2013, Colorimetric determination of magnesium in blood and saliva in Oral squamous cell carcinoma and potentially malignant disorders by titan yellowmethod. J Orofac Res 3(4):240– 244
Aziz NZ, Arathi K, Prasad BG, Desai D, Shetty SJ, Shahid M, 2018, Evaluation of magnesium levels in blood and saliva of oral squamous cell carcinoma and potentially malignant disorders by xylidyl blue method. J Oral Maxillofac Pathol 22(1):147–162
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2001
EP 2002
DI 10.1007/s12253-019-00750-w
PG 2
ER
PT J
AU Son, JH
Choi, JE
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Mutation and Expression of a Candidate Tumor Suppressor Gene EPB41L3 in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE EPB41L3; Mutation; Expression; Colon cancer; Gastric cancer
ID EPB41L3; Mutation; Expression; Colon cancer; Gastric cancer
AB Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) is candidate tumor suppressor gene (TSG) in various cancers. EPB41L3 downregulation has been identified in many solid cancers including gastric (GC) and colorectal cancers (CRCs), but somatic inactivating mutation along with protein expression in cancers are largely unexplored. The aim of our study was to find whether EPB41L3 gene was mutated and expressionally altered in GC and CRC. EPB41L3 gene has a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 124 CRCs, and found that only one CRC with MSI-H (1.3%) harbored the frameshift mutation within the repeat. In immunohistochemistry, loss of EPB41L3 expression was identified in 49%of GCs and 42%of CRCs. Our data may indicate EPB41L3 that loss of expression but not frameshift mutation may play a role in GC and CRC development by inhibiting TSG functions of EPB41L3.
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Wang Z, Zhang J, Ye M, Zhu M, Zhang B, Roy M, Liu J, An X, 2014, Tumor suppressor role of protein 4.1B/DAL-1. CellMol Life Sci 71:4815–4830
Wang H, Xu M, Cui X, Liu Y, Zhang Y, Sui Y, Wang D, Peng L, Wang D, Yu J, 2016, Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer. Sci Rep 6:21755
Ohno N, Terada N, Murata S, Yamakawa H, Newsham IF, Katoh R, OharaO,Ohno S, 2004, Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium. Histochem Cell Biol 122:579–586
Xue F, An C, Chen L, Liu G, Ren F, Guo X, Sun H,Mei L, Sun X, Li J, Tang Y, An X, Zheng P, 2019, 4.1B suppresses cancer cell proliferation by binding to EGFR P13 region of intracellular juxtamembrane segment. Cell Commun Signal 17:115
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Je EM, Kim MR, Min KO, Yoo NJ, Lee SH, 2012, Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131:E1044–E1047
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2003
EP 2005
DI 10.1007/s12253-019-00787-x
PG 3
ER
PT J
AU Mo, YH
Choi, JE
Yoo, JN
Lee, HS
AF Mo, Yoon Ha
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Mutational alterations of TDRD 1, 4 and 9 genes in colorectal cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Mo, Yoon Ha] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Jiang Y, Liu L, Shan W, Yang ZQ, 2016, An integrated genomic analysis of Tudor domain-containing proteins identifies PHD finger protein 20-like 1, PHF20L1, as a candidate oncogene in breast cancer. Mol Oncol 10:292–302
GuijoM, Ceballos-Chavez M, Gomez-Marin E, Basurto-Cayuela L, Reyes JC, 2017, Expression of TDRD9 in a subset of lung carcinomas by CpG island hypomethylation protects from DNA damage. Oncotarget 9:9618–9631
Boormans JL, Korsten H, Ziel-van der Made AJ, van Leenders GJ, de Vos CV, Jenster G, Trapman J, 2013, Identification of TDRD1 as a direct target gene of ERG in primary prostate cancer. Int J Cancer 133:335–345
Yoon H, Lee H, Kim HJ, You KT, Park YN, Kim H, Kim H, 2011, Tudor domain-containing protein 4 as a potential cancer/testis antigen in liver cancer. Tohoku J Exp Med 224:41–46
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
McGranahan N, Swanton C, 2015, Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27: 15–26
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2007
EP 2008
DI 10.1007/s12253-020-00798-z
PG 2
ER
PT J
AU Mehemmai, Ch
Cherbal, F
Hamdi, Y
Guedioura, A
Benbrahim, W
Bakour, R
Abdelhak, S
AF Mehemmai, Chiraz
Cherbal, Farid
Hamdi, Yosr
Guedioura, Abdelmoumene
Benbrahim, Wassila
Bakour, Rabah
Abdelhak, Sonia
TI Correction to: BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Page 1, under Abstract section, lines 11–12 should be rewritten as: Interestingly, we also detected a BRCA1 exon 15 deletion in two unrelated young female TNBC patients with strong family history of breast/ovarian cancer.
C1 [Mehemmai, Chiraz] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Cherbal, Farid] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Hamdi, Yosr] University of Tunis El Manar, Institut Pasteur de Tunis, Laboratory of Biomedical Genomics and Oncogenetics (LRTI, IPT 05)Tunis, Tunisia.
[Guedioura, Abdelmoumene] USTHB, Faculty of Biological Sciences, LOBEMAlgiers, Algeria.
[Benbrahim, Wassila] Anti-cancer center of BatnaBatna, Algeria.
[Bakour, Rabah] USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, El Alia, Bab Ezzouar, 16111 Algiers, Algeria.
[Abdelhak, Sonia] University of Tunis El Manar, Institut Pasteur de Tunis, Laboratory of Biomedical Genomics and Oncogenetics (LRTI, IPT 05)Tunis, Tunisia.
RP Cherbal, F (reprint author), USTHB, Faculty of Biological Sciences, Laboratory of Molecular and Cellular Biology, Unit of Genetics, 16111 Algiers, Algeria.
EM farid.cherbal@gmail.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2009
EP 2010
DI 10.1007/s12253-019-00586-4
PG 2
ER
PT J
AU Kim, U
Kim, CY
Lee, MJ
Oh, H
Ryu, B
Kim, J
Park, JH
AF Kim, Ukjin
Kim, C-Yoon
Lee, Min Ji
Oh, Hanseul
Ryu, Bokyeong
Kim, Jin
Park, Jae-Hak
TI Correction to: Phloretin Inhibits the Human Prostate Cancer Cells through the Generation of Reactive Oxygen Species
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Correction to: Pathology & Oncology Research https://doi.org/10.1007/s12253-019-00643-y The original version of this article unfortunately contained an error in Figs. 1, 5 and 6. The asterisks and bars indicating statistical significance were missing in the figures. The corrected Figs. 1, 5 and 6 are shown below. The original article has been corrected.
C1 [Kim, Ukjin] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Kim, C-Yoon] Konkuk University, School of Medicine, Department of Stem Cell Biology, 05029 Seoul, South Korea.
[Lee, Min Ji] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Oh, Hanseul] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Ryu, Bokyeong] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Kim, Jin] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
[Park, Jae-Hak] Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
RP Park, JH (reprint author), Seoul National University, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, 08826 Seoul, South Korea.
EM pjhak@snu.ac.kr
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2011
EP 2012
DI 10.1007/s12253-019-00643-y
PG 2
ER
PT J
AU Mohamed, EZAF
El, ZIK
Toni, DMN
AF Mohamed, El-Zahraa Ammar Fatma
El, Zahraa Ibrahim Khalil
Toni, D M Nisreen
TI Correction to: Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Correction to: Pathology & Oncology Research https://doi.org/10.1007/s12253-019-00755-5 The original version of this article unfortunately contained an error. The Tables 1 and 2 were missing in the published paper. The missing Tables 1 and 2 are shown in the next page. The original article has been corrected.
C1 [Mohamed, El-Zahraa Ammar Fatma] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
[El, Zahraa Ibrahim Khalil] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
[Toni, D M Nisreen] Minia University, Faculty of Medicine, Pathology DepartmentMinia, Egypt.
RP El, ZIK (reprint author), Minia University, Faculty of Medicine, Pathology Department, Minia, Egypt.
EM zahraa333eg@gmail.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2013
EP 2014
DI 10.1007/s12253-019-00790-2
PG 2
ER
PT J
AU Zheng, J
Xu, T
Feng, Ch
Zhang, Y
AF Zheng, Jing
Xu, Tingting
Feng, Chen
Zhang, Ying
TI Correction to: MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Correction to: Pathology & Oncology Research(2019)25:1181–1190 https://doi.org/10.1007/s12253-018-0552-z The original version of this article unfortunately contained an error in the affiliation section. The affiliation should have been Department of Respiratory Medicine, Taizhou Municiple Hospital, Zhejiang, China. The corrected affiliation is shown below.
C1 [Zheng, Jing] Taizhou Municiple Hospital, Department of Respiratory MedicineZhejiang, China.
[Xu, Tingting] Taizhou Municiple Hospital, Department of Respiratory MedicineZhejiang, China.
[Feng, Chen] Taizhou Municiple Hospital, Department of Respiratory MedicineZhejiang, China.
[Zhang, Ying] Taizhou Municiple Hospital, Department of Respiratory MedicineZhejiang, China.
RP Xu, T (reprint author), Taizhou Municiple Hospital, Department of Respiratory Medicine, Zhejiang, China.
EM Xu_tingting09@126.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2020
VL 26
IS 3
BP 2015
EP 2015
DI 10.1007/s12253-020-00794-3
PG 1
ER
PT J
AU Lee, EJ
Zhu, Z
Bai, Q
Brady, JT
Xiao, H
Wakefield, RM
Fang, Y
AF Lee, E Jacob
Zhu, Ziwen
Bai, Qian
Brady, J Tucker
Xiao, Huaping
Wakefield, R Mark
Fang, Yujiang
TI The Role of Interleukin-9 in Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Interleukin 9; Cancer; Inflammation
ID Interleukin 9; Cancer; Inflammation
AB Interluekin-9 (IL-9) is produced predominantly by helper T cells such as Th2 and Th9 cells. It normally functions through the activation of a JAK/STAT pathway and plays a critical role in immunity and the pathogenesis of cancer. In cancer, it yields different responses depending on the cancer cell line involved. This review is a summary of what is known about the involvement of IL-9 in various cancer cell lines as well as its role in immunity with a focus on allergic responses.
C1 [Lee, E Jacob] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, Iowa, USA.
[Zhu, Ziwen] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Bai, Qian] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Brady, J Tucker] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, Iowa, USA.
[Xiao, Huaping] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, Iowa, USA.
[Wakefield, R Mark] University of Missouri, School of Medicine, Department of SurgeryColumbia, MO, USA.
[Fang, Yujiang] Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, Iowa, USA.
RP Fang, Y (reprint author), Des Moines University, College of Osteopathic Medicine, Department of Microbiology, Immunology & Pathology, 50312 Des Moines, USA.
EM yujiang.fang@dmu.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2017
EP 2022
DI 10.1007/s12253-019-00665-6
PG 6
ER
PT J
AU Qin, J
Wen, B
Liang, Y
Yu, W
Li, H
AF Qin, Jingchun
Wen, Bin
Liang, Yuqi
Yu, Weitao
Li, Huixuan
TI Histone Modifications and their Role in Colorectal Cancer (Review)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Histone modification; Colorectal cancer; Histone acetylation; Histone methylation; Histone phosphorylation
ID Histone modification; Colorectal cancer; Histone acetylation; Histone methylation; Histone phosphorylation
AB The development of colorectal cancer is a complex and multistep process mediated by a variety of factors including the dysregulation of genetic and epigenetic under the influence of microenvironment. It is evident that epigenetics that affects gene activity and expression has been recognized as a critical role in the carcinogenesis. Aside from DNA methylation, miRNA level, and genomic imprinting, histone modification is increasingly recognized as an essential mechanism underlying the occurrence and development of colorectal cancer. Aberrant regulation of histone modification like acetylation, methylation and phosphorylation levels on specific residues is implicated in a wide spectrum of cancers, including colorectal cancer. In addition, as this process is reversible and accompanied by a plethora of deregulated enzymes, inhibiting those histone-modifying enzymes activity and regulating its level has been thought of as a potential path for tumor therapy. This review provides insight into the basic information of histone modification and its application in the colorectal cancer treatment, thereby offering new potential targets for treatment of colorectal cancer.
C1 [Qin, Jingchun] Guangzhou University of Chinese Medicine, Institute of Spleen and Stomach, 510000 Guangzhou, China.
[Wen, Bin] Guangzhou University of Chinese Medicine, Institute of Spleen and Stomach, 510000 Guangzhou, China.
[Liang, Yuqi] Guangzhou University of Chinese Medicine, Institute of Spleen and Stomach, 510000 Guangzhou, China.
[Yu, Weitao] Lianyungang Affiliated Hospital of Nanjing University of Traditional Chinese MedicineNanjing, China.
[Li, Huixuan] Guangzhou University of Chinese Medicine, Institute of Spleen and Stomach, 510000 Guangzhou, China.
RP Wen, B (reprint author), Guangzhou University of Chinese Medicine, Institute of Spleen and Stomach, 510000 Guangzhou, China.
EM wenbin@gzucm.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2023
EP 2033
DI 10.1007/s12253-019-00663-8
PG 11
ER
PT J
AU Kraboth, Z
Kalman, B
AF Kraboth, Zoltan
Kalman, Bernadette
TI Longitudinal Characteristics of Glioblastoma in Genome-Wide Studies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Glioblastoma; Sequential samples; Molecular evolution; Genomics; Transcriptomics; Epigenomics
ID Glioblastoma; Sequential samples; Molecular evolution; Genomics; Transcriptomics; Epigenomics
AB Glioblastoma is one of the deadliest tumors with barely over one-year median survival despite intensive efforts in defining its molecular characteristics and searching for innovative treatment strategies. While major progress has been made in cataloging cross-sectional genomic, transcriptomic and epigenomic features of the tumor, and inferring its main molecular pathways and niches for potential targeted intervention, we still do not have sufficient knowledge concerning evolutionary patterns and dynamics of molecular changes or the treatment-induced effects affecting glioblastoma biology. In this review, we summarize the results of recent longitudinal genomic, transcriptomic and epigenomic studies that brought us closer to a better understanding of this lethal disease. Evidence suggests that neuronal / glioma stem cells with accumulating mutations initiate glioblastoma development and recurrence, but the hypothetical models describing the courses that lead to established tumors have not been fully proven. Moving from the histopathological phenotype to the results of high resolution OMICS studies, we try to synthesize the currently available information from sequential glioblastoma analyses in order to highlight its multifaceted features and heterogeneity, as well as the expected complexity of potential treatment strategies that might once succeed.
C1 [Kraboth, Zoltan] University of Pecs, Department of Neurology, 12. Szigeti street, 7624 Pecs, Hungary.
[Kalman, Bernadette] University of Pecs, Department of Neurology, 12. Szigeti street, 7624 Pecs, Hungary.
RP Kalman, B (reprint author), University of Pecs, Department of Neurology, 7624 Pecs, Hungary.
EM Kalman.bernadett@markusovszky.hu;Bernadette.kalman@pte.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2035
EP 2047
DI 10.1007/s12253-019-00705-1
PG 13
ER
PT J
AU Raffone, A
Travaglino, A
Santoro, A
Esposito, I
Angelico, G
Spadola, S
Zannoni, FG
AF Raffone, Antonio
Travaglino, Antonio
Santoro, Angela
Esposito, Italia
Angelico, Giuseppe
Spadola, Saveria
Zannoni, Franco Gian
TI Accuracy of One-Step Nucleic Acid Amplification in Detecting Lymph Node Metastases in Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE OSNA; Sentinel lymph node; Endometrial cancer; Intraoperative; Ultrastaging; Tailored medicine
ID OSNA; Sentinel lymph node; Endometrial cancer; Intraoperative; Ultrastaging; Tailored medicine
AB One-step nucleic acid amplification (OSNA) is used to intraoperatively detect sentinel lymph node metastases in breast cancer. OSNA has also been proposed in endometrial cancer, but evidence in this regard is unclear to define the diagnostic accuracy of OSNA in detecting lymph node metastases in endometrial cancer. A systematic review and meta-analysis was performed by searching 8 electronic databases from their inception to March 2019 for studies testing the diagnostic accuracy of OSNA in detecting sentinel lymph node metastasis in endometrial cancer. Pathologic ultrastaging was the reference standard. Sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curve were calculated. Four studies with 237 patients and 691 lymph nodes were included. OSNA showed sensitivity = 0.88, specificity = 0.93, LR + =17.95, LR- = 0.15, DOR = 191.23 and high diagnostic accuracy (AUC = 0.959). OSNA appears as a highly accurate tool for intraoperative assessment of sentinel lymph node in endometrial cancer.
C1 [Raffone, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Santoro, Angela] Catholic University of the Sacred Heart, Agostino Gemelli University Polyclinic, Pathology Unit, Department of Woman and Child HealthRome, Italy.
[Esposito, Italia] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Angelico, Giuseppe] Catholic University of the Sacred Heart, Agostino Gemelli University Polyclinic, Pathology Unit, Department of Woman and Child HealthRome, Italy.
[Spadola, Saveria] Catholic University of the Sacred Heart, Agostino Gemelli University Polyclinic, Pathology Unit, Department of Woman and Child HealthRome, Italy.
[Zannoni, Franco Gian] Catholic University of the Sacred Heart, Agostino Gemelli University Polyclinic, Pathology Unit, Department of Woman and Child HealthRome, Italy.
RP Raffone, A (reprint author), University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, 80131 Naples, Italy.
EM anton.raffone@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2049
EP 2056
DI 10.1007/s12253-019-00727-9
PG 8
ER
PT J
AU Gargallo, P
Yanez, Y
Juan, A
Segura, V
Balaguer, J
Torres, B
Oltra, S
Castel, V
Canete, A
AF Gargallo, Pablo
Yanez, Yania
Juan, Antonio
Segura, Vanessa
Balaguer, Julia
Torres, Barbara
Oltra, Silves
Castel, Victoria
Canete, Adela
TI Review: Ewing Sarcoma Predisposition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Ewing sarcoma; Cancer predisposition; Genetic susceptibility; Polymorphism
ID Ewing sarcoma; Cancer predisposition; Genetic susceptibility; Polymorphism
AB Ewing sarcoma is a rare tumor developed in bone and soft tissues of children and teenagers. This entity is biologically led by a chromosomal translocation, typically including EWS and FLI1 genes. Little is known about Ewing sarcoma predisposition, although the role of environmental factors, ethnicity and certain polymorphisms on Ewing sarcoma susceptibility has been studied during the last few years. Its prevalence among cancer predisposition syndromes has also been thoroughly examined. This review summarizes the available evidence on predisposing factors involved in Ewing sarcoma susceptibility. On the basis of these data, an integrated approach of the most influential factors on Ewing sarcoma predisposition is proposed.
C1 [Gargallo, Pablo] La Fe Hospital, Clinical and Translational Oncology Research Group, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain.
[Yanez, Yania] La Fe Hospital, Clinical and Translational Oncology Research Group, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain.
[Juan, Antonio] La Fe Hospital, Pediatric Oncology and Hematology UnitValencia, Spain.
[Segura, Vanessa] La Fe Hospital, Clinical and Translational Oncology Research Group, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain.
[Balaguer, Julia] La Fe Hospital, Pediatric Oncology and Hematology UnitValencia, Spain.
[Torres, Barbara] La Fe Hospital, Pediatric Oncology and Hematology UnitValencia, Spain.
[Oltra, Silves] La Fe Hospital, Genetics UnitValencia, Spain.
[Castel, Victoria] La Fe Hospital, Pediatric Oncology and Hematology UnitValencia, Spain.
[Canete, Adela] La Fe Hospital, Pediatric Oncology and Hematology UnitValencia, Spain.
RP Gargallo, P (reprint author), La Fe Hospital, Clinical and Translational Oncology Research Group, 46026 Valencia, Spain.
EM gargallo_pabtat@gva.es
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2057
EP 2066
DI 10.1007/s12253-019-00765-3
PG 10
ER
PT J
AU Travaglino, A
Raffone, A
Gencarelli, A
Mollo, A
Guida, M
Insabato, L
Santoro, A
Zannoni, FG
Zull, F
AF Travaglino, Antonio
Raffone, Antonio
Gencarelli, Annarita
Mollo, Antonio
Guida, Maurizio
Insabato, Luigi
Santoro, Angela
Zannoni, Franco Gian
Zull, Fulvio
TI TCGA Classification of Endometrial Cancer: the Place of Carcinosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Cancer; Endometrium; Prognosis; Risk assessment; PROMISE; Treatment
ID Cancer; Endometrium; Prognosis; Risk assessment; PROMISE; Treatment
AB In 2013, The Cancer Genome Atlas (TCGA) Research Network found four novel prognostic subgroups of endometrial carcinoma: POLE/ultramutated (POLE), microsatellite-instable/hypermutated (MSI), copy-number-low/TP53-wild-type (CNL), and copy-number-highTP53-mutant (CNH). However, poor is known regarding uncommon histotypes of endometrial cancer. We aimed to assess the genetic profile of uterine carcinosarcoma (UCS) on the light of these findings. A systematic review and metaanalysis was performed through electronic databases searching (up to July 2019). All studies assessing UCS series for the TCGA classification were included. For each TCGA subgroup, pooled prevalence on the total UCS number was calculated. Four studies with 231 patients were included. Pooled prevalence of the TCGA subgroups were: 5.3% for the POLE subgroup, 7.3% for the MSI subgroup, 73.9% for the CNH subgroup, 13.5% for the CNL subgroup. The CNH subgroup predominates in UCS, while subgroups with high mutational load (POLE and MSI) are less common. UCS appears as a preferential evolution of CNH carcinomas.
C1 [Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Raffone, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Gencarelli, Annarita] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Mollo, Antonio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Guida, Maurizio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Insabato, Luigi] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology UnitNaples, Italy.
[Santoro, Angela] Agostino Gemelli University Polyclinic, Catholic University of the Sacred Heart, Department of Woman and Child HealthRome, Italy.
[Zannoni, Franco Gian] Agostino Gemelli University Polyclinic, Catholic University of the Sacred Heart, Department of Woman and Child HealthRome, Italy.
[Zull, Fulvio] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
RP Raffone, A (reprint author), University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Gynecology and Obstetrics Unit, 80131 Naples, Italy.
EM anton.raffone@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2067
EP 2073
DI 10.1007/s12253-020-00829-9
PG 7
ER
PT J
AU Travaglino, A
Pace, M
Varricchio, S
Russo, D
Pugliese, N
Severino, A
Picardi, M
Pane, F
Insabato, L
Staibano, S
Mascolo, M
AF Travaglino, Antonio
Pace, Mirella
Varricchio, Silvia
Russo, Daniela
Pugliese, Novella
Severino, Alessandro
Picardi, Marco
Pane, Fabrizio
Insabato, Luigi
Staibano, Stefania
Mascolo, Massimo
TI Involvement of Helicobacter Pylori in Ocular Adnexa Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Orbit; Ocular adnexa; Lymphoma; Helicobacter pylori; Antibiotic; Extranodal
ID Orbit; Ocular adnexa; Lymphoma; Helicobacter pylori; Antibiotic; Extranodal
AB Helicobacter pylori has been proposed as a possible etiologic factor of ocular adnexa lymphoma (OAL), although with conflicting results. To assess the involvement of H. pylori in OAL, as (1) H. pylori DNA positivity on OAL specimens, and (2) prevalence of H. pylori gastric infection in patients with OAL. A systematic review of studies assessing H. pylori in patients with OAL was conducted by searching electronic databases from their inception toMay 2019. Pooled positivity for H. pylori in OAL specimens detected by polymerase chain reaction, and pooled prevalence of H. pylori gastric infection,were calculatedwith 95% confidence interval (CI). Eleven studies with 308 patients were included. Pooled positivity for H. pylori was 16.8% in all OALs and 22.7% in MALT OAL, with high heterogeneity among studies. Pooled prevalence of H. pylori gastric infection in patients with OAL was 34.7%, with low statistical heterogeneity. In conclusion, H. pylori seems to be involved in a subset of OAL, but the heterogeneity found needs to be investigated in further studies. The prevalence of H. pylori gastric infection in patients with OAL does not seem to differ from that of the general population.
C1 [Travaglino, Antonio] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Pace, Mirella] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Varricchio, Silvia] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Russo, Daniela] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Pugliese, Novella] University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Hematology SectionNaples, Italy.
[Severino, Alessandro] University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Hematology SectionNaples, Italy.
[Picardi, Marco] University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Hematology SectionNaples, Italy.
[Pane, Fabrizio] University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Hematology SectionNaples, Italy.
[Insabato, Luigi] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Staibano, Stefania] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
[Mascolo, Massimo] University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, Via Sergio Pansini, 5, 80131 Naples, Italy.
RP Mascolo, M (reprint author), University of Naples Federico II, School of Medicine, Department of Advanced Biomedical Sciences, Anatomic Pathology Unit, 80131 Naples, Italy.
EM mmascol@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2075
EP 2081
DI 10.1007/s12253-020-00848-6
PG 7
ER
PT J
AU Patai, BB
Peterfy, N
Szakacs, N
Sapi, Z
Hetthessy, RJ
AF Patai, Bettina Bernadett
Peterfy, Nora
Szakacs, Noemi
Sapi, Zoltan
Hetthessy, Reka Judit
TI Papillary Endothelial Hyperplasia (Masson Tumor) of the Hand. Surgical and Pathological Consideration from Seven Cases Using New Vascular Markers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE Hand; Soft tissue lesion; Vascular tumor; Vascular malformation; Intravascular papillary endothelial hyperplasia; IPEH; Masson tumor
ID Hand; Soft tissue lesion; Vascular tumor; Vascular malformation; Intravascular papillary endothelial hyperplasia; IPEH; Masson tumor
AB Although papillary endothelial hyperplasia may occur at almost any site, one of the most common sites is the hand. It is generally regarded as a reactive vascular proliferation i.e. exuberant form of organizing thrombus. Diagnosis of Masson tumor can be challenging due to its close clinical, radiological and even histopathological resemblance to angiosarcoma. We present seven cases ofMasson tumor of the hand; wanting to reveal its nature using new vascular markers and discuss the treatment options and expected outcomes, present clinical and radiological features that may aid diagnosis and also offer treatment plans. A multicenter retrospective study was performed between January 2014 and November 2019. Immunohistochemical stains of Glut1, WT1, ERG, CD31 and alpha smooth muscle actin (ASMA) were performed on each cases. We found seven cases during the examined period. 4 out of 7 cases were women. All lesions occurred in the hands. 3 out of 7 cases appeared in a previously present vascular malformation. All cases were treated with surgical excision and the diagnosis of papillary endothelial hyperplasia was made by histology. Pre-operative testing (radiograph/MRI/US/fine needle aspiration biopsy) did not suggest the diagnosis of Masson tumor; however, aspiration cytology could rule out malignancy. The proliferative endothelial cells proved to be Glut1 negative and WT1 positive and the accompanying pericytic cells were ASMA positive in all cases. Though Masson tumor is a rare vascular lesion in the hand among other vascular tumors, it should be considered in the differential diagnostics even in the case of previously existing vascular malformation.WT1 positivity of the endothelial cells and the accompanying pericytic cells raises the question whether the initially reactive endothelial proliferation may transform into a true benign vascular tumor.
C1 [Patai, Bettina Bernadett] Military Health Centre, Department of TraumatologyBudapest, Hungary.
[Peterfy, Nora] Saint John’s Hospital, Department of Traumatology and Hand surgeryBudapest, Hungary.
[Szakacs, Noemi] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Hetthessy, Reka Judit] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
RP Hetthessy, RJ (reprint author), Semmelweis University, Department of Orthopedics, Budapest, Hungary.
EM doktorno@kezklinika.hu
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Vito Pesce,1 Davide Bizzoca,1 Angela Notarnicola,1 Andrea Piazzolla,1 Giovanni Vicenti, 1 Antonietta Cimmino,2Francesco Fortarezza,2 Giuseppe Maccagnano, 1 Giuseppe Solarino,1 and Biagio Moretti1, 2018, An intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma: A case report and literature review SAGE Open Med Case Rep.; 6: 2050313X17752851
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2083
EP 2090
DI 10.1007/s12253-020-00838-8
PG 8
ER
PT J
AU Molla, S
Hembram, ChK
Chatterjee, S
Nayak, D
Sethy, Ch
Pradhan, R
Kundu, NCh
AF Molla, Sefinew
Hembram, Chandra Krushna
Chatterjee, Subhajit
Nayak, Deepika
Sethy, Chinmayee
Pradhan, Rajalaxmi
Kundu, Nath Chanakya
TI PARP inhibitor Olaparib Enhances the Apoptotic Potentiality of Curcumin by Increasing the DNA Damage in Oral Cancer Cells through Inhibition of BER Cascade
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral cancer; Olaparib; Curcumin; PARP inhibitor; PARylation
ID Oral cancer; Olaparib; Curcumin; PARP inhibitor; PARylation
AB Although Olaparib (Ola, a PARP-inhibitor), in combination with other chemotherapeutic agents, was clinically approved to treat prostate cancer, but cytotoxicity, off-target effects of DNA damaging agents limit its applications in clinic. To improve the anticancer activity and to study the detailed mechanism of anti-cancer action, here we have used bioactive compound curcumin (Cur) in combination with Ola. Incubation of Ola in Cur pre-treated cells synergistically increased the death of oral cancer cells at much lower concentrations than individual optimum dose and inhibited the topoisomerase activity. Short exposure of Cur caused DNA damage in cells, but more increased DNA damage was noticed when Ola has incubated in Cur pre-treated cells. This combination did not alter the major components of homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways but significantly altered both short patch (SP) and long patch (LP) base excision repair (BER) components in cancer cells. Significant reduction in relative luciferase activity, expression of BER components and PARylation after Cur and Ola treatment confirmed this combination inhibit the BER activity in cells. Reduction of PARylation, decreased expression of BER components, decreased tumor volume and induction of apoptosis were also noticed in Cur + Ola treated Xenograft mice model. The combination treatment of Cur and Ola also helped in recovering the body weight of tumor-bearing mice. Thus, Cur + Ola combination increased the oral cancer cells death by not only causing the DNA damage but also blocking the induction of BER activity.
C1 [Molla, Sefinew] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Hembram, Chandra Krushna] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Chatterjee, Subhajit] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Nayak, Deepika] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Sethy, Chinmayee] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Pradhan, Rajalaxmi] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
[Kundu, Nath Chanakya] Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, Campus-11, Patia, 751024 Bhubaneswar, Odisha, India.
RP Kundu, NCh (reprint author), Deemed to be University, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Cancer Biology Division, 751024 Bhubaneswar, India.
EM cnkundu@gmail.com;cnkundu@kiitbiotech.ac.in
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2091
EP 2103
DI 10.1007/s12253-019-00768-0
PG 13
ER
PT J
AU Kato, K
Miyazawa, H
Kobayashi, H
Noguchi, N
Lambert, D
Kawashiri, Sh
AF Kato, Koroku
Miyazawa, Hiroki
Kobayashi, Hisano
Noguchi, Natsuyo
Lambert, Daniel
Kawashiri, Shuichi
TI Caveolin-1 Expression at Metastatic Lymph Nodes Predicts Unfavorable Outcome in Patients with Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Caveolin-1; p16; Oral squamous cell carcinoma; Metastatic lymph node; Prognosis
ID Caveolin-1; p16; Oral squamous cell carcinoma; Metastatic lymph node; Prognosis
AB We evaluated the clinical and prognostic value of the protein expression of caveolin-1 (CAV1) and p16 at the primary site and metastatic lymph nodes of oral squamous cell carcinoma (OSCC). Primary site specimens from 80 OSCC cases were randomly selected and lymph node specimens from 15 preserved metastatic lymph nodes from among those patients were selected for examination. We evaluated the CAV1 and p16 expression at both the primary site and metastatic lymph nodes, and analyzed the patients’ clinicopathological data in relation to CAV1 and p16 expression. Our analysis revealed significant positive correlations between CAV1 expression at the primary site and pathological metastasis, cell differentiation, and mode of invasion (p = 0.019, p = 0.002, p = 0.015, respectively), but p16 expression was not associated with any clinicopathological factors. Patients with high CAV1 expression at the primary sites showed significantly worse prognoses than those with low or negative CAV1 expression (p = 0.002), and multivariate analysis showed that the T-classification and CAV1 expression were independent OSCC prognostic factors. CAV1 expression was also present in the metastatic lymph nodes of the OSCC cases with particularly poor differentiation and high invasive grade, and patients with CAV1-positive metastatic lymph nodes showed significantly worse prognoses than those with CAV1-negative metastatic lymph nodes (p = 0.018). CAV1 may activate metastaticity and the invasive capacity of OSCC cells. CAV1 expression, particularly at metastatic lymph nodes, predicts a worse outcome for OSCC, suggesting that CAV1 could be used as a prognostic marker for OSCC.
C1 [Kato, Koroku] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Miyazawa, Hiroki] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Kobayashi, Hisano] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Noguchi, Natsuyo] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
[Lambert, Daniel] University of Sheffield, School of Clinical Dentistry, Unit of Oral and Maxillofacial PathologySheffield, UK.
[Kawashiri, Shuichi] Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
RP Kato, K (reprint author), Kanazawa University, Graduate School of Medical Science, Department of Oral and Maxillofacial Surgery, 920-8641 Kanazawa, Japan.
EM k-koroku@oral.m.kanazawa-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2105
EP 2113
DI 10.1007/s12253-019-00791-1
PG 9
ER
PT J
AU Oikawa, M
Tanaka, T
Narita, T
Noro, D
Iwamura, H
Tobisawa, Y
Yoneyama, T
Kodama, H
Hashimoto, Y
Koie, T
Ohyama, Ch
AF Oikawa, Masaaki
Tanaka, Toshikazu
Narita, Takuma
Noro, Daisuke
Iwamura, Hiromichi
Tobisawa, Yuki
Yoneyama, Tohru
Kodama, Hirotake
Hashimoto, Yasuhiro
Koie, Takuya
Ohyama, Chikara
TI Impact of the Proportion of Biopsy Positive Core in Predicting Biochemical Recurrence in Patients with Pathological Pt2 and Negative Resection Margin Status after Radical Prostatectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Organ-confined prostate cancer; Negative surgical margin; Radical prostatectomy; Biochemical recurrence; Proportion of biopsy positive core; Biopsy Gleason score
ID Organ-confined prostate cancer; Negative surgical margin; Radical prostatectomy; Biochemical recurrence; Proportion of biopsy positive core; Biopsy Gleason score
AB This study aimed to determine the prognostic factors associated with biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with pathological T2 (pT2) prostate cancer (PCa) and negative resection margin (RM) status at a single institution. In this retrospective study, we examined 386 patients who were diagnosed with pT2 PCa with negative RM after RP. The length of the tumor was provided for each biopsy core and the overall percentage of PCa was calculated by a pathologist at our institution. We estimated the BCR-free survival (BRFS) in these patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model to determine the risk factors of BCR. The median age of the participants was 68 years, and their initial prostate-specific antigen level was 6.55 ng/ml. The median follow-up period was 85.7 months. The 5-year BRFS rate of the participants was 89.0%. The 5-year BRFS rates were 89.8% in patients with a biopsy Gleason score of 6, 90.4% in those with 7, and 64.1% in those with ≥8 (P = 0.007). The BRFS rate was 93.3% in patients who had a biopsy positive core ≤20% and 82.0% in those who had ≥21% (P = 0.001). Based on the multivariate analysis, the proportion of biopsy positive core was significantly associated with BCR. The proportion of biopsy positive core may predict preoperative covariates in patients with pT2 PCa and negative RM status after RP.
C1 [Oikawa, Masaaki] Hakodate Municipal Hospital, Department of Urology, 041-8680 Hakodate, Japan.
[Tanaka, Toshikazu] Aomori Prefectural Central Hospital, Department of Urology, 030-8553 Aomori, Japan.
[Narita, Takuma] Hirosaki National Hospital, Department of Urology, 036-8545 Hirosaki, Japan.
[Noro, Daisuke] Mutsu General Hospital, Department of Urology, 035-8601 Mutsu, Japan.
[Iwamura, Hiromichi] Oyokyo Kidney Research Institute, Department of Urology, 038-0003 Aomori, Japan.
[Tobisawa, Yuki] Hirosaki University Graduate School of Medicine, Department of Urology, 036-8562 Hirosaki, Japan.
[Yoneyama, Tohru] Hirosaki University Graduate School of Medicine, Department of Urology, 036-8562 Hirosaki, Japan.
[Kodama, Hirotake] Tsugaru General Hospital, Department of Urology, 037-0074 Goshogawara, Japan.
[Hashimoto, Yasuhiro] Hirosaki University Graduate School of Medicine, Department of Urology, 036-8562 Hirosaki, Japan.
[Koie, Takuya] Gifu University Graduate School of Medicine, Department of Urology, Yanagito 1-1, 501-1194 Gifu, Japan.
[Ohyama, Chikara] Hirosaki University Graduate School of Medicine, Department of Urology, 036-8562 Hirosaki, Japan.
RP Koie, T (reprint author), Gifu University Graduate School of Medicine, Department of Urology, 501-1194 Gifu, Japan.
EM goodwin@gifui-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2115
EP 2121
DI 10.1007/s12253-019-00762-6
PG 7
ER
PT J
AU Kuthi, L
Somoracz,
Micsik, T
Jenei, A
Hajdu, A
Sejben, I
Imre, D
Posfai, B
Koczian, K
Semjen, D
Bajory, Z
Kulka, J
Ivanyi, B
AF Kuthi, Levente
Somoracz, Aron
Micsik, Tamas
Jenei, Alex
Hajdu, Adrienn
Sejben, Istvan
Imre, Daniel
Posfai, Boglarka
Koczian, Katalin
Semjen, David
Bajory, Zoltan
Kulka, Janina
Ivanyi, Bela
TI Clinicopathological Findings on 28 Cases with XP11.2 Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Translocation renal cell carcinoma; Xp11.2; Immunohistochemistry; TFE3 gene; Fluorescence in situ hybridization (FISH)
ID Translocation renal cell carcinoma; Xp11.2; Immunohistochemistry; TFE3 gene; Fluorescence in situ hybridization (FISH)
AB Xp11.2 translocation carcinoma is a distinct subtype of renal cell carcinoma characterized by translocations involving the TFE3 gene. Our study included the morphological, immunohistochemical and clinicopathological examination of 28 Xp11.2 RCCs. The immunophenotype has been assessed by using CA9, CK7, CD10, AMACR, MelanA, HMB45, Cathepsin K and TFE3 immunostainings. The diagnosis was confirmed by TFE3 break-apart FISH in 25 cases. The ages of 13 male and 15 female patients, without underlying renal disease or having undergone chemotherapy ranged from 8 to 72. The mean size of the tumors was 78.5mm. Forty-three percent of patients were diagnosed in the pT3/pT4 stage with distant metastasis in 6 cases. Histological appearance was branching-papillary composed of clear cells with voluminous cytoplasmin 13 and variable in 15 cases, including one tumor with anaplastic carcinoma and another with rhabdoid morphology. Three tumors were labeled with CA9, while CK7 was negative in all cases. Diffuse CD10 reaction was observed in 17 tumors and diffuse AMACR positivity was described in 14 tumors. The expression of melanocytic markers and Cathepsin K were seen only in 7 and 6 cases, respectively. TFE3 immunohistochemistry displayed a positive reaction in 26/28 samples. TFE3 rearrangement was detected in all the analyzed cases (25/ 25), including one with the loss of the entire labeled break-point region. The follow-up time ranged from 2 to 300 months, with 7 cancer-related deaths. In summary, Xp11.2 carcinoma is an uncommon form of renal cell carcinoma with a variable histomorphology and rather aggressive clinical course.
C1 [Kuthi, Levente] University of Szeged, Department of Pathology, 1 Allomas Street, H-6725 Szeged, Hungary.
[Somoracz, Aron] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jenei, Alex] University of Szeged, Department of Pathology, 1 Allomas Street, H-6725 Szeged, Hungary.
[Hajdu, Adrienn] University of Szeged, Department of Pathology, 1 Allomas Street, H-6725 Szeged, Hungary.
[Sejben, Istvan] Bacs-Kiskun County Hospital, Department of PathologyKecskemet, Hungary.
[Imre, Daniel] Hetenyi Geza County Hospital, Department of PathologySzolnok, Hungary.
[Posfai, Boglarka] University of Szeged, Department of OncotherapySzeged, Hungary.
[Koczian, Katalin] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Semjen, David] University of Pecs, Department of PathologyPecs, Hungary.
[Bajory, Zoltan] University of Szeged, Department of UrologySzeged, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Ivanyi, Bela] University of Szeged, Department of Pathology, 1 Allomas Street, H-6725 Szeged, Hungary.
RP Kuthi, L (reprint author), University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
EM kuthi.levente@med.u-szeged.hu
CR Argani P, Faria M, 2005, Translocation carcinomas of the kidney. Clin Lab Med 25:363–378
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Argani P, Antonescu CR, Couturier J et al, 2002, PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol 26:1553–1566
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Argani P, Ladanyi M, 2005, Translocation carcinomas of the kidney. Clin Lab Med 25:363–378
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Papp G, Nagy D, Sapi Z, 2017, Unusual signal patterns of breakapart FISH probes used in the Diagnosis of Soft Tissue Sarcomas. Pathol Oncol Res 23:863–871 34. Kato I, Furuya M, Baba M et al, 2019, RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review. Histopathology 75:254–265 35. Argani P, LadanyiM(2003, Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of the paediatric renal carcinomas. Pathology 35:492–498 36. Dal Cin P, Stas M, Sciot R et al, 1998, Translocation, X;1, reveals metastasis 31 years after renal cell carcinoma. Cancer Genet Cytogenet 101:58–61 37. Perot C, Bougaran J, Boccon-Gibod L et al, 1999, Two new cases of papillary renal cell carcinoma with t(X;1)(p11;q21, in females. Cancer Genet Cytogenet 110:54–56 38. Rais-Bahrami S, Drabick JJ, De Marzo AM et al, 2007, Xp11 translocation renal cell carcinoma: delayed but massive and lethal metastases of a chemotherapy-associated secondary malignancy. Urology 70:178e3–178e6 39. Mangel L, Biro K, Battyani I et al, 2015, A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression ofmetastatic renal cell carcinoma during pregnancy and after surgical abortion. BMC Cancer 15:1013 40. Patard JJ, Leray E, Rioux-Leclercq N et al, 2005, Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol 23:2763–2771
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2123
EP 2133
DI 10.1007/s12253-019-00792-0
PG 11
ER
PT J
AU Zhu, H
You, Y
Shen, Z
Shi, L
AF Zhu, Haifeng
You, Yongping
Shen, Zhouming
Shi, Lei
TI EGFRvIII-CAR-T Cells with PD-1 Knockout Have Improved Anti-Glioma Activity
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioblastoma multiform; EGFRvIII; CAR-T; PD-1; PD-L1
ID Glioblastoma multiform; EGFRvIII; CAR-T; PD-1; PD-L1
AB Glioblastoma multiforme (GBM) is the most malignant form of the brain tumors. EGFR variant III (EGFRvIII) is expressed in about 30% of GBM specimens, but not expressed in normal brain tissues. Therefore, EGFRvIII protein offers an ideal CAR-T therapeutic target for EGFRvIII-positive GBM patients. PD-L1 is expressed in a variety of cancer cells, including GBM. Tumor-associated PD-L1 can bind to PD-1 on T cells and promote apoptosis of T cells, thus suppressing the anti-cancer immune response. In our current studies, PD-1WT EGFRvIII-CAR-T cells and PD-1KD EGFRvIII-CAR-T cells were generated. Cytokine production and lytic activity of these two CAR-T cells against to PD-L1WT EGFRvIII+ U373 cells or PD-L1KO EGFRvIII+ U373 cells were evaluated. The results showed that PD-1KD EGFRvIII-CAR-T cells and PD-1WT EGFRvIII-CAR-T cells showed same levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) production as well as cytolytic activity against PD-L1KO EGFRvIII+ U373 cells; however, PD-1KD EGFRvIII-CAR-T cells exhibited higher levels of IFN-γ and IL-2 production as well as cytolytic activity against PD-L1+ EGFRvIII+ U373 cells than that of PD-1WT EGFRvIII-CAR-T cells. PD-1KD EGFRvIII-CAR-T cells also exhibited higher anti-glioma activity and longer survival in mice in vivo than that of PD-1WT EGFRvIII-CAR-T cells. Taken together, our findings indicate that PD-1 knockout enhances lytic activity of EGFRvIII-CAR-T cells against PD-L1+ EGFRvIII+ GBM cells. These might provide a new insight into strategy of GBM CAR-T cell therapy.
C1 [Zhu, Haifeng] Nanjing University, School of Medicine, Jinling Hospital, Department of Neurosurgery, 210029 Nanjing, China.
[You, Yongping] The First Affiliated Hospital of Nanjing Medical University, Department of Neurosurgery, 210029 Nanjing, China.
[Shen, Zhouming] Funing People’s Hospital, Department of Neurosurgery, 224400 Funing, China.
[Shi, Lei] Affiliated Kunshan Hospital of Jiangsu University, Department of Neurosurgery, 215300 Suzhou, China.
RP Shi, L (reprint author), Affiliated Kunshan Hospital of Jiangsu University, Department of Neurosurgery, 215300 Suzhou, China.
EM sl1012002322@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2135
EP 2141
DI 10.1007/s12253-019-00759-1
PG 7
ER
PT J
AU Szekerczes, T
Gogl, A
Illyes, I
Mandl, J
Borka, K
Kiss, A
Schaff, Zs
Lendvai, G
Werling, K
AF Szekerczes, Timea
Gogl, Aliz
Illyes, Ildiko
Mandl, Jozsef
Borka, Katalin
Kiss, Andras
Schaff, Zsuzsa
Lendvai, Gabor
Werling, Klara
TI Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Chronic hepatitis; autophagy; mitophagy; microRNA; immunohistochemistry
ID Chronic hepatitis; autophagy; mitophagy; microRNA; immunohistochemistry
AB Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and − 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and − 155 seem to be associated with CHC progression.
C1 [Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Gogl, Aliz] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Illyes, Ildiko] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Mandl, Jozsef] Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, 1094 Budapest, Hungary.
[Borka, Katalin] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Lendvai, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi 93, 1091 Budapest, Hungary.
[Werling, Klara] Semmelweis University, 2nd Department of Internal Medicine, 1088 Budapest, Hungary.
RP Lendvai, G (reprint author), Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
EM lendvai.gabor@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2143
EP 2151
DI 10.1007/s12253-020-00799-y
PG 9
ER
PT J
AU Lu, MY
Wang, WCh
Hou, TCh
Kuo, ChY
Lai, YCh
AF Lu, Meng-Yao
Wang, Wen-Chung
Hou, Tai-Cheng
Kuo, Chen-Yun
Lai, Yen-Chein
TI Methylation Statuses of H19DMR and KvDMR at WT2 in Wilms Tumors in Taiwan
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Multiplex ligation-dependent probe amplification; Nephroblastoma; Paternal uniparental disomy; Wilms tumor
ID Multiplex ligation-dependent probe amplification; Nephroblastoma; Paternal uniparental disomy; Wilms tumor
AB Wilms tumor is the most common pediatric renal malignancy. Several genetic loci have been shown to be associated with its formation. Genetic or epigenetic aberrations at WT1 and WT2 loci have been implicated in the etiology of the majority of sporadic Wilms tumors. In our previous study, most Wilms tumors tested negative for both constitutional mutations and somatic mutations in the WT1 gene. Thus, WT2 may play an important role in these tumors. In the present study, we analyzed the methylation statuses of WT2 at 11p15 using methylation sensitive multiplex ligation-dependent probe amplification in six Wilms tumors. Paternal uniparental disomy at WT2 was observed in two Wilms tumors with epithelial components due to hypermethylation at H19DMR and hypomethylation at KvDMR. Our findings highlight the benefits of testing for 11p15 epigenetic abnormalities to identify Wilms tumors with epithelial components.
C1 [Lu, Meng-Yao] National Taiwan University Hospital, Department of PediatricsTaipei, Taiwan, Republic of China.
[Wang, Wen-Chung] Jen-Ai Hospital, Department of Obstetrics and GynecologyTaichung, Taiwan, Republic of China.
[Hou, Tai-Cheng] Jen-Ai Hospital, Department of PathologyTaichung, Taiwan, Republic of China.
[Kuo, Chen-Yun] Jen-Ai Hospital, Department of PathologyTaichung, Taiwan, Republic of China.
[Lai, Yen-Chein] Chung Shan Medical University, Department of Medical Laboratory and Biotechnology, No.110, Sec. 1, Chien Kuo N. Road, 402 Taichung, Taiwan, Republic of China.
RP Lai, YCh (reprint author), Chung Shan Medical University, Department of Medical Laboratory and Biotechnology, 402 Taichung, Taiwan, Republic of China.
EM yenchein@csmu.edu.tw
CR Brown KW, Malik KT, 2001, The molecular biology of Wilms tumour. Expert Rev Mol Med 2001:1–16
Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E, 2006, Malignant renal tumours incidence and survival in European children, 1978-1997): report from the automated childhood Cancer information system project. Eur J Cancer 42:2103–2114
Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F et al, 2017, International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol 18:719– 731
Treger TD, Chowdhury T, Pritchard-Jones K, Behjati S et al, 2019, The genetic changes of Wilms tumour. Nat Rev Nephrol 15:240– 251
PDQ Pediatric Treatment Editorial Board, 2002)Wilms Tumor and Other Childhood Kidney Tumors Treatment, PDQ®): Health Professional Version. PDQ Cancer Information Summaries. Bethesda, MD): National Cancer Institute, US, 2002–2020
Gadd S, Huff V, Walz AL, Ooms A, Armstrong AE, Gerhard DS et al, 2017, A Children's oncology group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet 49: 1487–1494
Mahamdallie S, Yost S, Poyastro-Pearson E, Holt E, Zachariou A, Seal S et al, 2019, Identification of new Wilms tumour predisposition genes: an exome sequencing study. Lancet Child Adolesc Health 3:322–331
Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA et al, 1990, Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60: 509–520
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Al-Hussain T, Ali A, Akhtar M, 2014, Wilms tumor: an update. Adv Anat Pathol 21:166–173
Cardoso LC, Tenorio Castano JA, Pereira HS, Lima MA, Dos Santos AC, de Faria PS et al, 2012, Constitutional and somatic methylation status of DMRH19 and KvDMR in Wilms tumor patients. GenetMol Biol 35:714–724
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Scott RH, Douglas J, Baskcomb L, Huxter N, Barker K, Hanks S et al, 2008, Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat Genet 40:1329–1334
Lu MY, Wang WC, Lin CW, Chang A, Lai YC, 2014, Identification of a constitutional mutation in the WT1 gene in Taiwanese patients with Wilms tumor. Adv Biosci Biotechnol 5: 230–234
Chiang MR, Kuo CW, Wang WC, Hou TC, Kuo CY, Lu MYet al, 2019, Correlations between histological and array comparative genomic hybridization characterizations of Wilms tumor. Pathol Oncol Res 25:1199–1206
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Hubertus J, Lacher M, Rottenkolber M, Muller-Hocker J, Berger M, Stehr M et al, 2011, Altered expression of imprinted genes in Wilms tumors. Oncol Rep 25:817–823
Scott RH, Murray A, Baskcomb L, Turnbull C, Loveday C, Al- Saadi R et al, 2012, Stratification of Wilms tumor by genetic and epigenetic analysis. Oncotarget 3:327–335
VerschuurAC,VujanicGM,Van TinterenH, JonesKP, de Kraker J, Sandstedt B, 2010, Stromal and epithelial predominant Wilms tumours have an excellent outcome: the SIOP 93 01 experience. Pediatr Blood Cancer 55:233–238
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2153
EP 2159
DI 10.1007/s12253-020-00802-6
PG 7
ER
PT J
AU Yu, D
Ma, Y
Feng, Ch
Ma, Z
Guo, J
Chen, H
He, T
Guo, J
Sun, X
Qin, Q
Sun, X
Ma, J
AF Yu, Dingyue
Ma, Yuanyuan
Feng, Chen
Ma, Zhiyu
Guo, Jiayou
Chen, Hui
He, Tianli
Guo, Jiayi
Sun, Xingbang
Qin, Qin
Sun, Xinchen
Ma, Jianxin
TI PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oesophageal squamous cancer; PBX1; Radiosensitivity; STAT3
ID Oesophageal squamous cancer; PBX1; Radiosensitivity; STAT3
AB The radioresistance of oesophageal squamous cell carcinoma (OSCC) is a critical factor leading to a poor prognosis among patients. The expression of PBX1 is abnormally high in a broad range of human tissues, and this gene plays a key role in tumour proliferation. This research intended to explore the radiosensitization of OSCC by silencing PBX1. The OSCC cell lines KYSE450 and KYSE150 were subjected to PBX1 silencing and/or irradiation (IR). Cell proliferation, colony formation, and apoptosis were tested to evaluate the radiosensitization ability of PBX1 silencing. The levels of STAT3 and p-STAT3 in the OSCC cells were tested by Western blotting. Furthermore, KYSE150 cells with or without PBX1 silencing were xenografted into nude mice with or without radiation exposure. Concomitant PBX1 silencing and IR can obviously suppress growth and enhance radiosensitivity in OSCC cells and xenografts. Moreover, the downregulation of PBX1 inhibits the expression of STAT3 and p- STAT3. The downregulation of PBX1may increase radiosensitivity in OSCC cells and xenografts via the PBX1/STAT3 pathway. Our findings demonstrate that PBX1 may be a potential target for promoting the effect of radiation therapy in OSCC patients.
C1 [Yu, Dingyue] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Ma, Yuanyuan] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Feng, Chen] First Hospital of Bengbu Medical College, Oncology Department, 233000 Bengbu, AnHui, China.
[Ma, Zhiyu] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Guo, Jiayou] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Chen, Hui] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu, China.
[He, Tianli] Changxing People’s Hospital, Department of Respiratory, 313000 Huzhou, Zhejiang, China.
[Guo, Jiayi] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Sun, Xingbang] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
[Qin, Qin] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu, China.
[Sun, Xinchen] The First Affiliated Hospital of Nanjing Medical University, Department of Radiotherapy, 210000 Nanjing, Jiangsu, China.
[Ma, Jianxin] The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 57 Zhonghua West Road, 222042 Lian Yungang, Jiangsu Province, China.
RP Ma, J (reprint author), The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, Department of radiotherapy, 222042 Lian Yungang, China.
EM mjx3416@163.com
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, RebeloM et al, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. Int J Cancer 136(5):E359–E386
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2161
EP 2168
DI 10.1007/s12253-020-00803-5
PG 8
ER
PT J
AU Tang, X
He, Q
Sun, G
Qu, H
Liu, J
Gao, L
Shi, J
Ye, J
Liang, Y
AF Tang, Xiaolong
He, Qingsi
Sun, Guorui
Qu, Hui
Liu, Jia
Gao, Lei
Shi, Jingbo
Ye, Jianhong
Liang, Yahang
TI Total Tumor Volume Should be Considered as an Important Prognostic Factor for Synchronous Multiple Gastric Cancer Patients with Curative Gastrectomy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Tumor volume; Gastrectomy; Prognosis
ID Gastric cancer; Tumor volume; Gastrectomy; Prognosis
AB Synchronous multiple gastric cancer (SMGC) was a special type of gastric cancer with relatively low incidence. This article was designed to demonstrate that the total tumor volume (TTV) should be treated as an important prognostic factor in SMGC patients with curative gastrectomy. This study retrospective analyzed 140 SMGC patients who received curative gastrectomy between December 2004 and December 2014 in our hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed. This study applied univariate and multivariate analyses to identify the most significant prognostic factors. In the univariate analysis, the TTV, pTTVNM, pN stage, pT of main tumor were all significant prognostic factors in SMGC patients (all P < 0.05). In the multivariate analysis, pN stage, TTV and pTTVNM were confirmed to be independent prognostic factors (all P < 0.05). In the comparison of survival analysis, the pTTVNM stage system (P < 0.05) was superior to the pTNM stage system (P > 0.05) in SMGC patients. In conclusion, the TTV should be considered as an independent prognostic factor in overall survival in SMGC patients who received curative gastrectomy. The pTTVNM stage should be recommended as a suitable staging system for SMGC patients.
C1 [Tang, Xiaolong] Qilu Hospital of Shandong University, Department of General Surgery, No.107, West of Wenhua Street, Lixia District, 250012 Jinan, China.
[He, Qingsi] Qilu Hospital of Shandong University, Department of General Surgery, No.107, West of Wenhua Street, Lixia District, 250012 Jinan, China.
[Sun, Guorui] Qilu Hospital of Shandong University, Department of General Surgery, No.107, West of Wenhua Street, Lixia District, 250012 Jinan, China.
[Qu, Hui] Qilu Hospital of Shandong University, Department of General Surgery, No.107, West of Wenhua Street, Lixia District, 250012 Jinan, China.
[Liu, Jia] Qilu Hospital of Shandong University, Department of Health Management Center, 250012 Jinan, China.
[Gao, Lei] Qilu Hospital of Shandong University, 250011 Jinan, China.
[Shi, Jingbo] Qilu Hospital of Shandong University, 250011 Jinan, China.
[Ye, Jianhong] Qilu Hospital of Shandong University, 250011 Jinan, China.
[Liang, Yahang] Qilu Hospital of Shandong University, 250011 Jinan, China.
RP Sun, G (reprint author), Qilu Hospital of Shandong University, Department of General Surgery, 250012 Jinan, China.
EM doctorsungr@163.com
CR Isobe T, Hashimoto K, Kizaki J, Murakami N, Aoyagi K, Koufuji K, Akagi Y, Shirouzu K, 2013, Characteristics and prognosis of synchronous multiple early gastric cancer. World J Gastroenterol 19(41):7154–7159
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2169
EP 2175
DI 10.1007/s12253-020-00804-4
PG 7
ER
PT J
AU Xu, Y
Zhang, L
Wang, Q
Zheng, M
AF Xu, Yuting
Zhang, Lin
Wang, Qingling
Zheng, Maojin
TI Comparison of Different Colorectal Cancer With Liver Metastases Models Using Six Colorectal Cancer Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer cell lines; Liver metastases; Orthotopic model; Ectopic model
ID Colorectal cancer cell lines; Liver metastases; Orthotopic model; Ectopic model
AB At present, modeling methods of colorectal cancer with liver metastases have significant limitations. Here, we established orthotopic and ectopic hepatic metastases models using six colorectal cancer cell lines to choose an ideal animal model for studying colorectal cancer growth and liver metastases. Luciferin-expressing six colorectal cancer cell lines were used to induce animal models of colorectal cancer with liver metastases by intra-splenic injection or implantation of tumor tissue in the caecum. Tumors growth and metastatic events were observed by bioluminescence imaging. In orthotopic transplantation group, six cell lines all had taken rates of 100%for orthotopic tumors but showed variations in rates of growth. HCT-116 cell developed the 50% liver metastases. However, the ectopic transplantation group achieved higher liver metastatic rate, with the highest frequencies for HCT116 cell (90%) and SW620 cell (77.8%). Furthermore, the time to develop liver metastases and survival rates of bearing tumor mice were shorter than orthotopic transplantation group. Additionally, six colorectal cancer cell lines resulted in more lymph node metastases in orthotopic transplantation group, whereas produced widespread peritoneal seeding in ectopic transplantation group. Bioluminescence imaging and pathological findings confirmed the growth and metastatic characteristics of tumors. Two animal models of colorectal cancer using six cell lines showed highly variations in rates of growth, survival rates of bearing-tumor mice and frequencies of metastases. The study provides useful information for the establishment of clinically relevant colorectal cancer with liver metastases animal models.
C1 [Xu, Yuting] Xuzhou Medical University, Department of Pathology, 221004 Xuzhou, Jiangsu, China.
[Zhang, Lin] Xuzhou Medical University, Department of Pathology, 221004 Xuzhou, Jiangsu, China.
[Wang, Qingling] Xuzhou Medical University, Department of Pathology, 221004 Xuzhou, Jiangsu, China.
[Zheng, Maojin] Xuzhou Medical University, Department of Pathology, 221004 Xuzhou, Jiangsu, China.
RP Xu, Y (reprint author), Xuzhou Medical University, Department of Pathology, 221004 Xuzhou, China.
EM xyt325@xzhmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2177
EP 2183
DI 10.1007/s12253-020-00805-3
PG 7
ER
PT J
AU Guo, J
Cui, Z
Zheng, Y
Li, X
Chen, Y
AF Guo, Junying
Cui, Zhaolei
Zheng, Yuhong
Li, Xiaoli
Chen, Yan
TI Comparison of Epstein-Barr Virus Serological Tools for the Screening and Risk Assessment of Nasopharyngeal Carcinoma: a Large Population-based Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nasopharyngeal carcinoma; Epstein-Barr virus; VCA-IgA; EA-IgA; Rta-IgG; Serological screening; Diagnostic efficiency; ROC curve analysis
ID Nasopharyngeal carcinoma; Epstein-Barr virus; VCA-IgA; EA-IgA; Rta-IgG; Serological screening; Diagnostic efficiency; ROC curve analysis
AB Epstein-Barr virus (EBV)-based serologic antibody testing has been found to be a feasible alternative for nasopharyngeal carcinoma (NPC) screening in endemic areas. The purpose of this study was to evaluate the performance of ELISA based on VCA IgA antibody, EA-IgA and Rta-IgG antibody specific to EBV in the diagnosis of NPC. A total of 2155 untreated NPC patients and 6957 healthy volunteers without nasopharyngeal disorder were recruited, and all subjects received EBV VCA-IgA, EA-IgA and Rta-IgG antibody tests simultaneously. The diagnostic efficiency of three testing alone or in combination for the diagnosis of NPC was evaluated. The prevalence of IgA antibody against EBV-VCA, IgA antibody against EBV-EA and IgG antibody against EBV-Rta was 89.9%, 46.6% and 63.2%. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 89.88%, 89.65%, 73.18%, 96.63% and 0.79 for the EBV VCA-IgA antibody test, 46.59%, 96.89%, 82.5%, 85.42%and 0.43 for the EA-IgA antibody test, and 63.25%, 94.87%, 79.48%, 89.29%and 0.58 for the Rta-IgG antibody test in the diagnosis of NPC, and ROC curve analysis revealed the greatest diagnostic efficiency for EBV VCA-IgA antibody test and the lowest efficiency for EBV EA-IgA antibody test in the diagnosis of NPC. In addition, the simultaneous triple positivity of VCA-IgA, EA-IgA and Rta-IgG antibodies specific to EBV indicated the highest risk of NPC, and the simultaneous triple negativity of the three types of anti-EBV antibodies suggested the lowest risk of NPC. Our data demonstrate that EBV VCA-IgA antibody test shows a higher diagnostic efficiency than EA-IgA and Rta-IgG antibody tests for the screening of NPC, and triple positivity of is a better biomarker for the diagnosis of NPC.
C1 [Guo, Junying] Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, No. 420 Fuma Road, 350014 Fuzhou, Fujian Province, China.
[Cui, Zhaolei] Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, No. 420 Fuma Road, 350014 Fuzhou, Fujian Province, China.
[Zheng, Yuhong] Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, No. 420 Fuma Road, 350014 Fuzhou, Fujian Province, China.
[Li, Xiaoli] Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, No. 420 Fuma Road, 350014 Fuzhou, Fujian Province, China.
[Chen, Yan] Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, No. 420 Fuma Road, 350014 Fuzhou, Fujian Province, China.
RP Chen, Y (reprint author), Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fujian Provincial Key Laboratory of Tumor Biotherapy, 350014 Fuzhou, China.
EM 19895758592@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2185
EP 2190
DI 10.1007/s12253-020-00808-0
PG 6
ER
PT J
AU Malusecka, E
Chmielik, E
Suwinski, R
Giglok, M
Lange, D
Rutkowski, T
Mazurek, MA
AF Malusecka, Ewa
Chmielik, Ewa
Suwinski, Rafal
Giglok, Monika
Lange, Dariusz
Rutkowski, Tomasz
Mazurek, M Agnieszka
TI Significance of HPV16 Viral Load Testing in Anal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HPV; HPV16 viral load; p16INK4A; p53
ID HPV; HPV16 viral load; p16INK4A; p53
AB Human papilloma virus (HPV) is highly frequent among patients with anal squamous cell carcinoma, but the viral load (VL) differs between patients. This study aimed to compare the rate of HPV positivity, HPV16VL, p16INK4A and p53 expression between treatment naive and recurrent anal cancer patients. HPV was genotyped via AmpliSens® HPV HCR-genotype-titre-FRT kit. HPV16 VL was determined via quantitative polymerase chain reaction-based in-house test. p16INK4A and p53 expression was tested via immunohistochemistry. The cohort comprised 13 treatment-naive and 17 recurrent anal SCC patients. High-risk HPV was detected in 87% of cases, and HPV16 (73%) was the predominant genotype. The rate of HPV positivity was higher among women and nonsmokers, and majority of HPV-positive cases were also p16INK4A-positive. All p53-negative tumors were HPV16-positive. The most predominant p53 staining pattern in the HPV-positive group was scattered type, whereas it was diffuse type in the HPV-negative group. The HPV16 VL was higher in the treatment-naive group. Further, in the treatment-naive group, cases with scattered staining pattern of p53 had higher HPV16 VL than cases with diffuse staining pattern. The opposite result was noted in the recurrent cancer group. Moreover, p16-positive cases with scattered p53 staining pattern in the treatment naive group had higher HPV16 VL than their counterparts in the recurrent cancer group. In conclusion, the HPV VL, as is the association between VL and p16INK4A /p53, is in an inversed trend in treatment naive and recurrent cancer patients, highlighting the importance of HPV VL measurement in anal SCC.
C1 [Malusecka, Ewa] Maria Sklodowska-Curie National Research Institute of Oncology, Center for Translational Research and Molecular Biology of Cancer, Gliwice Branch, 44-102 Gliwice, Poland.
[Chmielik, Ewa] Maria Sklodowska-Curie National Research Institute of Oncology, Tumor Pathology DepartmentGliwice, Poland.
[Suwinski, Rafal] Maria Sklodowska-Curie National Research Institute of Oncology, II Radiotherapy and Chemotherapy Clinic and Teaching HospitalGliwice, Poland.
[Giglok, Monika] Maria Sklodowska-Curie National Research Institute of Oncology, II Radiotherapy and Chemotherapy Clinic and Teaching HospitalGliwice, Poland.
[Lange, Dariusz] Maria Sklodowska-Curie National Research Institute of Oncology, Tumor Pathology DepartmentGliwice, Poland.
[Rutkowski, Tomasz] Maria Sklodowska-Curie National Research Institute of Oncology, I Radiation and Clinical Oncology DepartmentGliwice, Poland.
[Mazurek, M Agnieszka] Maria Sklodowska-Curie National Research Institute of Oncology, Center for Translational Research and Molecular Biology of Cancer, Gliwice Branch, 44-102 Gliwice, Poland.
RP Malusecka, E (reprint author), Maria Sklodowska-Curie National Research Institute of Oncology, Center for Translational Research and Molecular Biology of Cancer, 44-102 Gliwice, Poland.
EM Ewa.Malusecka@io.gliwice.pl
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2191
EP 2199
DI 10.1007/s12253-020-00801-7
PG 9
ER
PT J
AU Geczi, L
Bodoky, Gy
Rokszin, Gy
Fabian, I
Torday, L
AF Geczi, Lajos
Bodoky, Gyorgy
Rokszin, Gyorgy
Fabian, Ibolya
Torday, Laszlo
TI Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastatic renal cell carcinoma; Axitinib; Sequential therapy; VEGF inhibitors; Overall survival
ID Metastatic renal cell carcinoma; Axitinib; Sequential therapy; VEGF inhibitors; Overall survival
AB Background: Targeted therapies significantly improve clinical outcomes among patients with metastatic renal cell carcinoma (mRCC). Several new agents have been approved for first- and second-line use. However, there is a lack of compelling evidence comparing sequencing strategies, and available comparative data regarding the real-world effectiveness of different therapeutic sequences are limited. Materials and Methods: We identified mRCC patients who initiated targeted therapy between January 1, 2008 and May 31, 2017 from the National Health Insurance Fund (NHIF) database of Hungary. Overall survival (OS) and duration of first-line treatment (DFT) were obtained for patients receiving sunitinib-everolimus, sunitinib-axitinib, or pazopanib-everolimus treatment sequences. OS of sunitinib-everolimus and sunitinib-axitinib sequences was also determined for patients having better or worse response to sunitinib first-line therapy. Results: Median OS was significantly longer among patients treated with sunitinib-axitinib compared to those receiving sunitinib-everolimus. Median DFT was also significantly longer in the sunitinib-axitinib vs. sunitinib-everolimus group. Sunitinib-axitinib was associated with significantly longer median OS compared to sunitinib-everolimus in patients with better response to first-line sunitinib in the pooled sunitinib population. In patients with worse response to sunitinib, sunitinib-axitinib was associated with a trend towards greater OS compared to sunitinib-everolimus, but the difference did not reach statistical significance. Conclusions: In this nationwide database analysis, mRCC patients treated with the sunitinib-axitinib sequence had significantly longer OS compared to those receiving sunitinib-everolimus therapy. The OS benefits of second-line axitinib were consistent among patients with better response to sunitinib defined by DFT values.
C1 [Geczi, Lajos] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy u. 7–9, 1122 Budapest, Hungary.
[Bodoky, Gyorgy] Egyesitett Szent Istvan es Szent Laszlo Korhaz, Onkologiai Osztaly, Albert Florian ut 5, 1097 Budapest, Hungary.
[Rokszin, Gyorgy] RxTarget Ltd, Bacso Nandor ut 10, 5000 Szolnok, Hungary.
[Fabian, Ibolya] RxTarget Ltd, Bacso Nandor ut 10, 5000 Szolnok, Hungary.
[Torday, Laszlo] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, 6720 Szeged, Hungary.
RP Geczi, L (reprint author), National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, 1122 Budapest, Hungary.
EM gelajos@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2201
EP 2207
DI 10.1007/s12253-020-00809-z
PG 7
ER
PT J
AU Galamb, O
Kalmar, A
Sebestyen, A
Danko, T
Kriston, Cs
Furi, I
Hollosi, P
Csabai, I
Wichmann, B
Krenacs, T
Bartak, KB
Nagy, BZs
Zsigrai, S
Barna, G
Tulassay, Zs
Igaz, P
Molnar, B
AF Galamb, Orsolya
Kalmar, Alexandra
Sebestyen, Anna
Danko, Titanilla
Kriston, Csilla
Furi, Istvan
Hollosi, Peter
Csabai, Istvan
Wichmann, Barnabas
Krenacs, Tibor
Bartak, Kinga Barbara
Nagy, Brigitta Zsofia
Zsigrai, Sara
Barna, Gabor
Tulassay, Zsolt
Igaz, Peter
Molnar, Bela
TI Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE LINC00152; CYTOR; Long non-codingRNA; Colorectal cancer; Colorectal adenoma
ID LINC00152; CYTOR; Long non-codingRNA; Colorectal cancer; Colorectal adenoma
AB Up-regulation of the long non-coding RNA LINC00152 can contribute to cancer development, proliferation and invasion, including colorectal cancer, however, its mechanism of action in colorectal carcinogenesis and progression is only insufficiently understood. In this work we correlated LINC00152 expression with promoter DNA methylation changes in colorectal tissues along the normal-adenoma-carcinoma sequence and studied the effects of LINC00152 silencing on the cell cycle regulation and on the whole transcriptome in colon carcinoma cells using cell and molecular biology techniques. LINC00152 was significantly up-regulated in adenoma and colorectal cancer (p < 0.001) compared to normal samples, which was confirmed by real-time PCR and in situ hybridization. LINC00152 promoter hypomethylation detected in colorectal cancer (p < 0.01) was strongly correlated with increased LINC00152 expression (r=-0.90). Silencing of LINC00152 significantly suppressed cell growth, induced apoptosis and decreased cyclin D1 expression (p < 0.05). Whole transcriptome analysis of LINC00152-silenced cells revealed significant down-regulation of oncogenic and metastasis promoting genes (e.g. YES proto-oncogene 1, PORCN porcupine Oacyltransferase), and up-regulation of tumour suppressor genes (e.g. DKK1 dickkopfWNTsignalling pathway inhibitor 1, PERP p53 apoptosis effector) (adjusted p < 0.05). Pathway analysis confirmed the LINC00152-related activation of oncogenic molecular pathways including those driven by PI3K/Akt, Ras, WNT, TP53, Notch and ErbB. Our results suggest that promoter hypomethylation related overexpression of LINC00152 can contribute to the pathogenesis of colorectal cancer by facilitating cell progression through the up-regulation of several oncogenic and metastasis promoting pathway elements.
C1 [Galamb, Orsolya] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kriston, Csilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Furi, Istvan] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Hollosi, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csabai, Istvan] Eotvos Lorand University, Department of Physics of Complex SystemsBudapest, Hungary.
[Wichmann, Barnabas] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Bartak, Kinga Barbara] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Nagy, Brigitta Zsofia] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Zsigrai, Sara] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Tulassay, Zsolt] Hungarian Academy of Sciences, Molecular Medicine Research GroupBudapest, Hungary.
[Igaz, Peter] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
[Molnar, Bela] Semmelweis University, Szentkiralyi str 46, 1088 Budapest, Hungary.
RP Galamb, O (reprint author), Semmelweis University, 1088 Budapest, Hungary.
EM udvardyne_galamb.orsolya@semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2209
EP 2223
DI 10.1007/s12253-020-00800-8
PG 15
ER
PT J
AU Beer, A
Taghizadeh, H
Schiefer, AI
Puhr, H
Karner, A
Jomrich, G
Schoppmann, S
Kain, R
Preusser, M
Ilhan-Mutlu, A
AF Beer, Andrea
Taghizadeh, Hossein
Schiefer, Ana-Iris
Puhr, C. Hannah
Karner, K. Alexander
Jomrich, Gerd
Schoppmann, F. Sebastian
Kain, Renate
Preusser, Matthias
Ilhan-Mutlu, Aysegul
TI PD-L1 and HER2 Expression in Gastroesophageal Cancer: a Matched Case Control Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastroesophageal tumor; Esophageal tumor; Gastroesophageal junction tumor; Gastric tumor; PD-L1; HER2; Immunotherapy; TPS; CPS
ID Gastroesophageal tumor; Esophageal tumor; Gastroesophageal junction tumor; Gastric tumor; PD-L1; HER2; Immunotherapy; TPS; CPS
AB Immunotherapy with check-point inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumors. Human epidermal growth factor receptor 2 (HER2) is the only identified therapeutic target in upper GI tumors, whose potential interaction with programmed death-ligand 1 (PD-L1) is unknown. The aim of this study was the investigation of PD-L1 and HER2 in upper GI tumors.We retrospectively identified patients with HER2 positive gastroesophageal cancers and matched them with a HER2 negative group. We investigated the tumor specimens for HER2 status and PD-L1 expression, with the following assessments being performed: i) staining of tumor cells in terms of tumor proportion score (TPS), ii) staining for tumorassociated immune cells (TAIs), iii) interface pattern and iv) combined positive score (CPS). Both HER2 positive and negative group consisted of 59 patients. Expression of PD-L1 in TAIs and interface pattern were associated with a favorable outcome (p = 0.02, HR = 0.8; p = 0.04, HR = 0.39; respectively) in patients with localized disease, whereas TPS was associated with an unfavorable outcome in patients with advanced tumor (p = 0.02, HR = 1.4). These effects were HER2 independent. PD-L1 expression in its different assessment is equally observed in HER2 positive and negative patients. Future studies will show whether dual inhibition of HER2 and PD-L1 improves survival of this selected patient population.
C1 [Beer, Andrea] Medical University of Vienna, Department of PathologyVienna, Austria.
[Taghizadeh, Hossein] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Schiefer, Ana-Iris] Medical University of Vienna, Department of PathologyVienna, Austria.
[Puhr, C. Hannah] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Karner, K. Alexander] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Jomrich, Gerd] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Schoppmann, F. Sebastian] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Kain, Renate] Medical University of Vienna, Department of PathologyVienna, Austria.
[Preusser, Matthias] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
[Ilhan-Mutlu, Aysegul] Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors UnitVienna, Austria.
RP Ilhan-Mutlu, A (reprint author), Medical University of Vienna, Comprehensive Cancer Center Vienna, Upper GI Tumors Unit, Vienna, Austria.
EM aysegul.ilhan@meduniwien.ac.at
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Janjigian YY, Sanchez-Vega F, Jonsson P, Chatila WK, Hechtman JF, Ku GY, Riches JC, Tuvy Y, Kundra R, Bouvier N, Vakiani E, Gao J, Heins ZJ, Gross BE, Kelsen DP, Zhang L, Strong VE, Schattner M, Gerdes H, Coit DG, Bains M, Stadler ZK, Rusch VW, Jones DR, Molena D, Shia J, Robson ME, Capanu M, Middha S, Zehir A, Hyman DM, Scaltriti M, Ladanyi M, Rosen N, Ilson DH, Berger MF, Tang L, Taylor BS, Solit DB, Schultz N, 2018, Genetic predictors of response to systemic therapy in Esophagogastric Cancer. Cancer Discov 8(1):49–58. https://doi. org/10.1158/2159-8290.CD-17-0787
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2225
EP 2235
DI 10.1007/s12253-020-00814-2
PG 11
ER
PT J
AU Qadir, J
Majid, S
Khan, M
Rashid, F
Wani, DM
Din, I
Bashir, H
AF Qadir, Jasiya
Majid, Sabhiya
Khan, S. Mosin
Rashid, Fouzia
Wani, Din Mumtaz
Din, Inshah
Bashir, Haamid
TI AT-rich Interaction Domain 1A Gene Variations: Genetic Associations and Susceptibility to Gastric Cancer Risk
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ARID1A; Gastric cancer; Pro912Thr; Gln944Lys; Gln920Ter; Kashmiri Population
ID ARID1A; Gastric cancer; Pro912Thr; Gln944Lys; Gln920Ter; Kashmiri Population
AB AT-rich interaction domain containing protein 1A (ARID1A), has recently emerged as a novel class of gene which acts as a potent tumor suppressor in numerous types of cancers such asGastric, Breast, Ovarian, Colorectal, Lung cancers. ARID1A is involved in the regulation of various cellular processes such as proliferation, differentiation and DNA repair, yet its association with the susceptibility of cancer remains unknown. Here, we aimed to analyse the association of the ARID1A variants (Pro912Thr, Gln944Lys and Gln920Ter) with the risk of Gastric cancer (GC) in Kashmiri population. The study included 103 confirmed cases of GC and 163 normal controls. The genotypes were studied using Polymerase Chain Reaction. Different bioinformatic predictive tools were also used to analyse the possible effect of these SNP’s on the resultant protein. The Pro912Thr and Gln920Ter variants of ARID1A showed significant difference in genotypic and allelic frequencies between the GC cases and controls (P < 0.05), whereas, the data did not reveal any correlation between Gln944Lys variant and Gastric cancer risk. Both Pro912Thr and Gln920Ter SNP’s follow “Dominant mode of inheritance”. In Silico analysis predicted that amino acid substitution of Pro912Thr SNP decreases the protein stability thus changing the functional properties of resultant protein, so backing the possibility of damaging effect of this SNP. Our study suggests that Pro912Thr and Gln920Ter SNP’s of ARD1A gene are associated with increased risk of GC in Kashmiri population.
C1 [Qadir, Jasiya] Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
[Majid, Sabhiya] Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
[Khan, S. Mosin] Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
[Rashid, Fouzia] University of Kashmir, Department of Clinical Biochemistry, 190006 Srinagar, India.
[Wani, Din Mumtaz] Government Medical College Srinagar and Associated Hospitals, Department of Surgery, 190010 Srinagar, India.
[Din, Inshah] Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
[Bashir, Haamid] Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
RP Majid, S (reprint author), Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry and Research Centre University of Kashmir, 190010 Srinagar, India.
EM sabuumajid@gmail.com
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Tavana Z, Khalili A, Namazi G, Ebrahimi A, Davoodi S, Alborizi S, Roozmeh S, 2018, Prevalence of common polymorphisms of AT-rich interaction domain 1A and endothelial nitric oxide synthase in patients with endometriosis compared to control group. J Endometriosis Pelvic Pain Disord 10:26–31
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2237
EP 2246
DI 10.1007/s12253-020-00815-1
PG 10
ER
PT J
AU Watanabe, T
Sato, K
Kono, T
Yamagishi, Y
Kumazawa, F
Miyamoto, M
Takano, M
Tsuda, H
AF Watanabe, Takanori
Sato, Kimiya
Kono, Takako
Yamagishi, Yoji
Kumazawa, Fumihisa
Miyamoto, Morikazu
Takano, Masashi
Tsuda, Hitoshi
TI Aquaporin 3 Expression in Endometrioid Carcinoma of the Uterine Body Correlated With Early Stage and Lower Grade
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Aquaporin; water channel; uterus; endometrioid carcinoma; immunohistochemistry
ID Aquaporin; water channel; uterus; endometrioid carcinoma; immunohistochemistry
AB Aquaporins (AQPs) are a family of transmembrane water channel proteins distributed in various human tissues. Recent studies revealed that AQPs play important roles in cancer biology. Few studies have documented the relationship between the prognosis, stage, and histological grade of uterine endometrioid carcinoma, with AQP expression. Hence, the present study aimed to investigate this relationship between uterine endometrioid carcinoma and AQP expression.We retrospectively reviewed records of the patients who underwent surgery for uterine body cancer between 1990 and 2010 at the National Defense Medical College Hospital, Saitama, Japan. In 241 cases of endometrioid carcinoma, we immunohistochemically examined the expression of AQP 1, 2, 3, 4, and 5, and their relationship with clinicopathological parameters and the patients’ prognosis. We investigated the relationship between the clinicopathological parameters and AQP3 expression, and found that as the FIGO stage and histological grade progressed, the percentage of AQP3 expression tends to decrease. Furthermore, we analyzed progression-free survival/ overall survival (PFS/OS) using the log-rank test, and found that the AQP3-positive group had a better prognosis than AQP3- negative group (PFS: P < 0.001, OS: P = 0.002, respectively). Using Cox’s univariate proportional hazard model, we revealed that AQP3 had a low hazard ratio. However, according to Cox’s multivariate proportional hazard model, AQP3 was not an independent prognostic factor. Among the endometrioid carcinoma patients, the AQP3-positive group was associated with early stage and lower grade compared to the AQP3-negative group. Therefore, AQP3 has the potential to serve as a predictor of prognosis, although further investigation is necessary to elucidate the biologicalmechanismofAQP3 in endometrioid carcinoma.
C1 [Watanabe, Takanori] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Sato, Kimiya] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Kono, Takako] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Yamagishi, Yoji] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Kumazawa, Fumihisa] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
[Miyamoto, Morikazu] National Defense Medical College, Department of Obstetrics and GynecologyTokorozawa, Saitama, Japan.
[Takano, Masashi] National Defense Medical College, Department of Obstetrics and GynecologyTokorozawa, Saitama, Japan.
[Tsuda, Hitoshi] National Defense Medical College, Department of Basic Pathology, 3-2 Namiki, 359-8513 Tokorozawa, Saitama, Japan.
RP Sato, K (reprint author), National Defense Medical College, Department of Basic Pathology, 359-8513 Tokorozawa, Japan.
EM kimiya@ndmc.ac.jp
CR Hori M, Matsuda T, Shibata A et al, 2015, Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan, MCIJ, project. Jpn J Clin Oncol 45:884–891
Verkman AS, 2005, More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118:3225–3232
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Verkman AS, Hara-Chikuma M, Papadopoulos MC, 2008, Aquaporins–new players in cancer biology. J Mol Med, Berl, 86: 523–529
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Pan H, Sun CC, Zhou CYet al, 2008, Expression of aquaporin-1 in normal, hyperplasic, and carcinomatous endometria. Int J Gynecol Obstet 101:239–244
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Rubenwolf PC, Denzinger S, Otto W, 2012, Aquaporin 3 protein expression in transitional cell carcinoma: a potential marker with regard to tumour progression and prognosis? Eur Urol 61:627–628
Rubenwolf PC, Otto W, Denzinger S et al, 2014, Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage.World J Urol 32:991–997
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Sato K, Miyamoto M, Takano M et al, 2018, Different prognostic implications of aquaporin-1 and aquaporin-5 expression among different histological types of ovarian carcinoma. Pathol Oncol. , DOI 10.1007/s12253-018-0456-y, in press)
Ji C, Cao C, Lu S et al, 2008, Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemother Pharmacol 62:857–865
He R, Han W, Hu Yet al, 2019, AQP2 is regulated by estradiol in human endometrium and is associated with spheroid attachment in vitro. Mol Med Rep 20:1306–1312
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2247
EP 2253
DI 10.1007/s12253-020-00813-3
PG 7
ER
PT J
AU Karaszi, K
Vigh, R
Mathe, M
Fullar, A
Olah, L
Fule, T
Papp, Z
Kovalszky, I
AF Karaszi, Katalin
Vigh, Renata
Mathe, Miklos
Fullar, Alexandra
Olah, Laszlone
Fule, Tibor
Papp, Zoltan
Kovalszky, Ilona
TI Aberrant Expression of Syndecan-1 in Cervical Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Syndecan-1; Cervical cancer; Survival analysis; Cancer-associated fibroblasts; Extracellularmatrix remodeling
ID Syndecan-1; Cervical cancer; Survival analysis; Cancer-associated fibroblasts; Extracellularmatrix remodeling
AB Syndecan-1, is a transmembrane heparan/chondroitin sulfate proteoglycan necessary for cell-cell and cell-matrix interactions. Its decreased level on the cell surface correlates with poor prognosis in several tumor types. Aberrant stromal localization of syndecan- 1 is also considered an unfavorable prognostic factor in various human malignancies. In the presented work the question was addressed if changes in syndecan-1 expression are related to the prognosis of cervical cancer. Immunohistochemistry for syndecan- 1 extracellular domain was performed on surgical specimens of primary cervical cancer. To follow the communication between tumor cells and stromal fibroblasts, their mono-and co-cultures were studied, detecting the expression of syndecan-1, smooth muscle actin, vimentin, and desmin. Immunohistochemistry of tumorous specimens revealed that while cell surface syndecan-1 expression was reduced on cancer cells, it appeared on the surface of tumor-associated fibroblasts. Until year 7, the cohort with high cell surface syndecan-1 expression had significantly longer survival. No difference in the same time-period could be detected when stromal syndecan-1 expression was analyzed. In vitro analysis revealed, that tumor cells can induce syndecan-1 expression on fibroblast, and fibroblasts showed that fibroblast-like cells are built by two cell types: (a) syndecan-1 positive, cytokeratin negative real fibroblasts, and (b) syndecan-1 and cytokeratin positive epithelial-mesenchymal transformed tumor cells. Syndecan-1 on the surface of cancer cells appears to be a positive prognostic marker. Although syndecan-1 positive fibroblasts promote tumor cell proliferation in vitro, we failed to detect their cancer promoting effect in vivo.
C1 [Karaszi, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Vigh, Renata] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Mathe, Miklos] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Fullar, Alexandra] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Olah, Laszlone] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Fule, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
[Papp, Zoltan] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, H-1082 Budapest, Hungary.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, H-1085 Budapest, Hungary.
RP Kovalszky, I (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, H-1085 Budapest, Hungary.
EM kovalelastic@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2255
EP 2264
DI 10.1007/s12253-020-00816-0
PG 10
ER
PT J
AU Viola, L
Londero, PA
Bertozzi, S
Orsaria, M
Marzinotto, S
Antoniazzi, F
Renda, V
Cinel, J
Fruscalzo, A
Lelle, JR
Mariuzzi, L
AF Viola, Luigi
Londero, P Ambrogio
Bertozzi, Serena
Orsaria, Maria
Marzinotto, Stefania
Antoniazzi, Fulvio
Renda, Valentina
Cinel, Jacqueline
Fruscalzo, Arrigo
Lelle, J Ralph
Mariuzzi, Laura
TI Prognostic Role of Kruppel-Like Factors 5, 9, and 11 in Endometrial Endometrioid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kruppel-like factors; KLF; KLF5; KLF11; KLF9; Endometrioid endometrial cancer; Endometrial cancer
ID Kruppel-like factors; KLF; KLF5; KLF11; KLF9; Endometrioid endometrial cancer; Endometrial cancer
AB Background and Objective: Kruppel-like factors (KLFs) are transcription factors with the ability to mediate cross-talk with signaling pathways involved in cell proliferation control, apoptosis, migration, and differentiation. They also appear to influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Our study aims to evaluate the potential prognostic role of KLF5, KLF9, and KLF11 in endometrial cancer, and their correlation with hormonal receptor status and cellular proliferation. Materials and Methods: Retrospective observational study on cases of endometrioid endometrial adenocarcinoma collected in the period January 2000–December 2011 at the University of Udine. Formalin-fixed, paraffin-embedded tissue samples were all submitted to tissue microarray immunohistochemical study. A survival analysis was performed. Results: One hundred forty seven patients were included in the study with a mean age at surgery of 65.6 years (±10.2). 80.3% of endometrial malignancies were classified as stage FIGO I (118/147). Radiation therapy and chemotherapy were administered in 62.3% (91/146) and 6.2% (9/145) of patients respectively. Five-year overall survival and disease-free survival resulted 85.4% (95% CI, 79.8–91.4%) and 79.4% (95% CI, 73.0–86.4%) respectively. A high Ki-67, cytoplasmatic KLF5 (HR 4.72, CI.95 1.61–13.89, p < 0.05), and nuclear KLF11 (HR 3.04, CI.95 0.99–9.36, p = 0.053) scores correlated with a shorter overall survival. In addition, a high nuclear KLF11 (HR 2.59, CI.95 1.13–5.95, p < 0.05) score correlated with a shorter disease-free survival. Conclusions: In patients affected by endometrioid endometrial carcinoma, higher staining levels of KLF5 and KLF11 correlated with a poorer prognosis. However, further studies are required in order to better clarify the role of KLFs in the natural history of endometrial cancer.
C1 [Viola, Luigi] University of Campania “Luigi Vanvitelli”, Radiology Department, 80138 Naples, Italy.
[Londero, P Ambrogio] University of Udine, DAME, Academic Hospital of Udine, Clinic of Obstetrics and Gynecology, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
[Bertozzi, Serena] Ennergi Research (Non-Profit Organization), 33050 Lestizza, Italy.
[Orsaria, Maria] University of Udine, DAME, Academic Hospital of Udine, Institute of Pathology, 33100 Udine, Italy.
[Marzinotto, Stefania] University of Udine, DAME, Academic Hospital of Udine, Institute of Pathology, 33100 Udine, Italy.
[Antoniazzi, Fulvio] University of Udine, DAME, Academic Hospital of Udine, Institute of Pathology, 33100 Udine, Italy.
[Renda, Valentina] University of Udine, DAME, Academic Hospital of Udine, Institute of Pathology, 33100 Udine, Italy.
[Cinel, Jacqueline] University of Udine, Academic Hospital of Udine, Clinic of Surgery, 33100 Udine, Italy.
[Fruscalzo, Arrigo] Christophorus-Kliniken, Clinic of Obstetrics and Gynecology, 48653 Coesfeld, Germany.
[Lelle, J Ralph] University Hospital of Munster, Clinic of Obstetrics and Gynecology, Albert-Schweitzer-Campus 1, Gebaude: A1, 48149 Munster, Germany.
[Mariuzzi, Laura] University of Udine, DAME, Academic Hospital of Udine, Institute of Pathology, 33100 Udine, Italy.
RP Londero, PA (reprint author), University of Udine, DAME, Academic Hospital of Udine, Clinic of Obstetrics and Gynecology, 33100 Udine, Italy.
EM ambrogio.londero@gmail.com
CR Allen NE, Key TJ, Dossus L, Rinaldi S, Cust A, Lukanova A, Peeters PH, Onland-Moret NC, Lahmann PH, Berrino F, Panico S, Larranaga N, Pera G, Tormo MJ, Sanchez MJ, Ramon Quiros J, Ardanaz E, Tjonneland A, Olsen A, Chang-Claude J, Linseisen J, Schulz M, Boeing H, Lundin E, Palli D, Overvad K, Clavel- Chapelon F, Boutron-Ruault MC, Bingham S, Khaw KT, Bas Bueno-de-Mesquita H, Trichopoulou A, Trichopoulos D, Naska A, Tumino R, Riboli E, Kaaks R, 2008, Endogenous sex hormones and endometrial cancer risk in women in the European prospective investigation into cancer and nutrition, EPIC). Endocr Relat Cancer 15:485–497
Lacey JV, Yang H, Gaudet MM, Dunning A, Lissowska J, Sherman ME et al, 2011, Endometrial cancer and genetic variation in PTEN, PIK3CA,AKT1,MLH1, andMSH2 within a populationbased case-control study. Gynecol Oncol 120:167–173
Simmen RCM, Pabona JMP, Velarde MC, Simmons C, Rahal O, Simmen FA, 2010, The emerging role of Kruppel-like factors in endocrine-responsive cancers of female reproductive tissues. J Endocrinol 204:223–231
Simmen RCM, Zhang XL, Michel FJ, Min SH, Zhao G, Simmen FA, 2002, Molecular markers of endometrial epithelial cell mitogenesis mediated by the Sp/Kruppel-like factor BTEB1. DNA Cell Biol 21:115–128
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Simmen FA, Su Y, Xiao R, Zeng Z, Simmen RCM, 2008, The Kruppel-like factor 9, KLF9, network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression. Reprod Biol Endocrinol 6:41
Mutter GL, Baak JP, Fitzgerald JT, Gray R, Neuberg D, Kust GA et al, 2001, Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation. Gynecol Oncol 83:177–185
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Pabona JMP, Velarde MC, Zeng Z, Simmen FA, Simmen RCM, 2009, Nuclear receptor co-regulator Kruppel-like factor 9 and prohibitin 2 expression in estrogen-induced epithelial cell proliferation in the mouse uterus. J Endocrinol 200:63–73
Velarde MC, Zeng Z, McQuown JR, Simmen FA, Simmen RCM, 2007, Kruppel-like factor 9 is a negative regulator of liganddependent estrogen receptor alpha signaling in Ishikawa endometrial adenocarcinoma cells. Mol Endocrinol 21:2988–3001
Pearson R, Fleetwood J, Eaton S, Crossley M, Bao S, 2008, Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol 40:1996–2001
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2265
EP 2272
DI 10.1007/s12253-020-00817-z
PG 8
ER
PT J
AU Tanaka, T
Miyamoto, Sh
Terada, Sh
Kogata, Y
Fujiwara, S
Tanaka, Y
Taniguchi, K
Komura, K
Yamamoto, K
Yamada, T
Ohmichi, M
AF Tanaka, Tomohito
Miyamoto, Shunsuke
Terada, Shinichi
Kogata, Yuhei
Fujiwara, Satoe
Tanaka, Yoshimichi
Taniguchi, Kohei
Komura, Kazumasa
Yamamoto, Kazuhiro
Yamada, Takashi
Ohmichi, Masahide
TI The Diagnostic Accuracy of an Intraoperative Frozen Section Analysis and Imprint Cytology of Sentinel Node Biopsy Specimens from Patients with Uterine Cervical and Endometrial Cancer: a Retrospective Observational Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Cervical cancer; Sentinel node biopsy; Frozen section; Imprint cytology
ID Endometrial cancer; Cervical cancer; Sentinel node biopsy; Frozen section; Imprint cytology
AB Sentinel node biopsy (SNB) may be a decision-making tool for function preservation surgery, including radical trachelectomy and ovary preservation in the treatment of cervical and endometrial cancer. The intraoperative diagnosis is important for guiding treatment decisions for patients with these conditions. Three hundred seventy-one patients with cervical and endometrial cancer received SNB with an intraoperative frozen section analysis and imprint cytology. The sentinel node was cut in half, parallel to the longest axis, to obtain the maximum section area. After performing imprint cytology, one half was used to create a frozen section. The specimen was cut at 2-mm intervals into 5-μm-thick sections, which were subjected to hematoxylin and eosin staining. The diagnostic accuracy of intraoperative frozen section analyses and imprint cytology was compared to the final pathological diagnosis. Among 951 detected sentinel nodes, 51 nodes were found to be positive in the final pathological diagnosis. The sensitivity of a frozen section analysis, imprint cytology and the combination of the two modalities was 76.5%, 72.6%, and 92.2%, respectively. The specificity of a frozen section analysis and imprint cytology was 100%. The negative predictive value of a frozen section analysis and imprint cytology was 98.7% and 98.5%, respectively. In these settings, the accuracy of the frozen section analysis and imprint cytology in the evaluation of SNB specimens was considered acceptable; however, the sensitivity of the combined approach was higher in comparison to when a frozen section analysis or imprint cytology was performed alone.
C1 [Tanaka, Tomohito] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Miyamoto, Shunsuke] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Terada, Shinichi] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Kogata, Yuhei] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Fujiwara, Satoe] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Tanaka, Yoshimichi] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
[Taniguchi, Kohei] Osaka Medical College, Translational Research ProgramTakatsuki, Osaka, Japan.
[Komura, Kazumasa] Osaka Medical College, Translational Research ProgramTakatsuki, Osaka, Japan.
[Yamamoto, Kazuhiro] Osaka Medical College, RadiologyTakatsuki, Osaka, Japan.
[Yamada, Takashi] Osaka Medical College, PathologyTakatsuki, Osaka, Japan.
[Ohmichi, Masahide] Osaka Medical College, Department of Obstetrics and Gynecology, 2-7, Daigaku-machi, 569-8686 Takatsuki, Osaka, Japan.
RP Tanaka, T (reprint author), Osaka Medical College, Department of Obstetrics and Gynecology, 569-8686 Takatsuki, Japan.
EM gyn123@osaka-med.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2273
EP 2279
DI 10.1007/s12253-020-00822-2
PG 7
ER
PT J
AU Benati, M
Montagnana, M
Danese, E
Mazzon, M
Paviati, E
Garzon, S
Lagana, SA
Casarin, J
Giudici, S
Raffaelli, R
Ghezzi, F
Franchi, M
Lippi, G
AF Benati, Marco
Montagnana, Martina
Danese, Elisa
Mazzon, Martina
Paviati, Elisa
Garzon, Simone
Lagana, Simone Antonio
Casarin, Jvan
Giudici, Silvia
Raffaelli, Ricciarda
Ghezzi, Fabio
Franchi, Massimo
Lippi, Giuseppe
TI Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial cancer; Endometrial hyperplasia; cfDNA; Telomere length; Diagnosis; Biomarkers
ID Endometrial cancer; Endometrial hyperplasia; cfDNA; Telomere length; Diagnosis; Biomarkers
AB To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than inHC (p < 0.0001). The diagnostic performance of cfDNA RTLwas estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79– 0.95, p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0%(95%CI: 64.35–90.95) and a specificity of 80.65%(95%CI: 62.53–92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.
C1 [Benati, Marco] University of Verona, Section of Clinical BiochemistryVerona, Italy.
[Montagnana, Martina] University of Verona, Section of Clinical BiochemistryVerona, Italy.
[Danese, Elisa] University of Verona, Section of Clinical BiochemistryVerona, Italy.
[Mazzon, Martina] AOUI Verona, Laboratory of Clinical Chemistry and HematologyVerona, Italy.
[Paviati, Elisa] University of Verona, Section of Clinical BiochemistryVerona, Italy.
[Garzon, Simone] University of Insubria, “Filippo Del Ponte” Hospital, Department of Obstetrics and Gynecology, Piazza Biroldi 1, 21100 Varese, Italy.
[Lagana, Simone Antonio] University of Insubria, “Filippo Del Ponte” Hospital, Department of Obstetrics and Gynecology, Piazza Biroldi 1, 21100 Varese, Italy.
[Casarin, Jvan] University of Insubria, “Filippo Del Ponte” Hospital, Department of Obstetrics and Gynecology, Piazza Biroldi 1, 21100 Varese, Italy.
[Giudici, Silvia] University of Verona, AOUI Verona, Department of Obstetrics and GynecologyVerona, Italy.
[Raffaelli, Ricciarda] University of Verona, AOUI Verona, Department of Obstetrics and GynecologyVerona, Italy.
[Ghezzi, Fabio] University of Insubria, “Filippo Del Ponte” Hospital, Department of Obstetrics and Gynecology, Piazza Biroldi 1, 21100 Varese, Italy.
[Franchi, Massimo] University of Verona, AOUI Verona, Department of Obstetrics and GynecologyVerona, Italy.
[Lippi, Giuseppe] University of Verona, Section of Clinical BiochemistryVerona, Italy.
RP Garzon, S (reprint author), University of Insubria, “Filippo Del Ponte” Hospital, Department of Obstetrics and Gynecology, 21100 Varese, Italy.
EM simone.garzon@yahoo.it
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2281
EP 2289
DI 10.1007/s12253-020-00819-x
PG 9
ER
PT J
AU Chai, YB
Yip, KW
Dusa, N
Mohtarrudin, N
Seow, FH
AF Chai, Yean Boon
Yip, Kien Wai
Dusa, Noraini
Mohtarrudin, Norhafizah
Seow, Fong Heng
TI Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE IL-17; IL-17RA; Colorectal carcinoma; Prognostic biomarker; Tumour progression
ID IL-17; IL-17RA; Colorectal carcinoma; Prognostic biomarker; Tumour progression
AB Interleukin-17 (IL-17) is a pro-inflammatory cytokine found in various cancers. Current evidence indicates that IL-17 plays a vital role in tumour initiation and progression in colorectal carcinoma (CRC) via binding with its receptor, IL-17RA. However, the association between clinicopathological features and presence of IL-17 and IL-17RA protein in primary CRC tissues remains unclear. This study also investigates the difference between the presence of IL-17 and IL-17RA in the paired tumour tissues versus adjacent normal tissues. The presence of IL-17RA and IL-17 protein in primary CRC tissues was determined by immunohistochemistry. Associations between clinicopathological features and IL-17RA and IL-17 immunoreactivity, were analyzed by χ2 tests. We found that both IL-17RA (p = 0.001) and IL-17 (p = 0.025) in tumour cells of primary CRC tissues was significantly lower as compared to adjacent normal tissue. Positive immunoreactivity for IL-17RA and IL-17 were detected in 51.0% and 16.8% of tumour tissues, respectively. Furthermore, negative immunoreactivity of IL-17R was significantly associated with advanced stage according to TNM classifier (p = 0.027), high grade of tumour (p = 0.019), increased depth of tumour invasion (p = 0.023) and vascular invasion (p = 0.039). Positive IL-17 immunoreactivity was associated with advanced stage (p = 0.008) and lymph node metastasis (p = 0.008). Thus, this study suggests that the loss of IL-17RA expression occurs as tumour progresses and this may predict the aggressiveness of tumour whilst expression of IL-17 promotes tumour progression and lymph node metastasis. Thus, loss of IL-17RA could be a useful prognostic biomarker for tumour progression in CRC patients.
C1 [Chai, Yean Boon] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Immunology Laboratory, 43400 Serdang, Selangor, Malaysia.
[Yip, Kien Wai] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Immunology Laboratory, 43400 Serdang, Selangor, Malaysia.
[Dusa, Noraini] Hospital Kuala Lumpur, Department of PathologyKuala Lumpur, Malaysia.
[Mohtarrudin, Norhafizah] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400 Serdang, Selangor, Malaysia.
[Seow, Fong Heng] Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Immunology Laboratory, 43400 Serdang, Selangor, Malaysia.
RP Seow, FH (reprint author), Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, Immunology Laboratory, 43400 Serdang, Malaysia.
EM shf@upm.edu.my
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2291
EP 2298
DI 10.1007/s12253-020-00820-4
PG 8
ER
PT J
AU Kakimoto, S
Miyamoto, M
Einama, T
Matsuura, H
Iwahashi, H
Ishibashi, H
Sakamoto, T
Hada, T
Takano, M
AF Kakimoto, Soichiro
Miyamoto, Morikazu
Einama, Takahiro
Matsuura, Hiroko
Iwahashi, Hideki
Ishibashi, Hiroki
Sakamoto, Takahiro
Hada, Taira
Takano, Masashi
TI Co-Expression of Mesothelin and CA125 Is Associated with the Poor Prognosis of Endometrial Serous Carcinoma and Mixed Carcinomas Including Serous Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrial carcinoma; Serous carcinoma; Mixed carcinoma; Mesothelin; CA125; Prognosis
ID Endometrial carcinoma; Serous carcinoma; Mixed carcinoma; Mesothelin; CA125; Prognosis
AB The aim of this study was to investigate the association between the clinicopathologic factors and either expression or coexpression of mesothelin and cancer antigen (CA) 125 in endometrial serous carcinoma and mixed carcinomas including serous carcinoma. Between 1990 and 2017, patients with endometrial serous carcinoma and mixed carcinoma including serous carcinoma treated by total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either expression or co-expression of mesothelin and CA125 was evaluated by immunochemical analysis and the clinicopathological features were retrospectively examined. Among the 40 patients included, 19, 31, and 18 patients exhibited single positive mesothelin, single positive CA125, and positive co-expression, respectively. The expression of mesothelin and CA125 was observed to be positively associated (p = 0.021). There was no significant association of age and FIGO stage with individual mesothelin or CA125 expression or their co-expression. Overall survival (OS), but not progression-free survivals (PFS), of only mesothelin-positive patientswas worse (p = 0.024). Hence, OS and PFS of patients with positive co-expression were worse (PFS: p = 0.043, OS: p = 0.012). In multivariate analysis, single mesothelin expression and single CA125 expression did not lead to worse prognosis. However, positive co-expression was the worst prognostic factor for OS (hazard ratio: 3.32, p = 0.039). Coexpression of mesothelin and CA125 may accurately predict OS in endometrial serous carcinoma and mixed carcinomas including serous carcinoma. Further studies should examine this relationship.
C1 [Kakimoto, Soichiro] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Miyamoto, Morikazu] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Einama, Takahiro] National DefenseMedical College Hospital, Department of Surgery, 359-8513 Tokorozawa, Saitama, Japan.
[Matsuura, Hiroko] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Iwahashi, Hideki] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Ishibashi, Hiroki] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Sakamoto, Takahiro] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Hada, Taira] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
[Takano, Masashi] National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Saitama, Japan.
RP Miyamoto, M (reprint author), National Defense Medical College, Department of Obstetrics and Gynecology, 359-8513 Tokorozawa, Japan.
EM mmiyamoto@ndmc.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2299
EP 2306
DI 10.1007/s12253-020-00823-1
PG 8
ER
PT J
AU Meszaros, N
Smanyko, V
Major, T
Stelczer, G
Janvary, ZsL
Kovacs, E
Baheri, M
Zaka, Z
Pukancsik, D
Takacsi-Nagy, Z
Polgar, Cs
AF Meszaros, Norbert
Smanyko, Viktor
Major, Tibor
Stelczer, Gabor
Janvary, Zsolt Levente
Kovacs, Eszter
Baheri, Maria
Zaka, Zoltan
Pukancsik, David
Takacsi-Nagy, Zoltan
Polgar, Csaba
TI Implementation of Stereotactic Accelerated Partial Breast Irradiation Using Cyber-Knife – Technical Considerations and Early Experiences of a Phase II Clinical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; APBI; SBRT; Cyber-knife; Phase II
ID Breast cancer; APBI; SBRT; Cyber-knife; Phase II
AB To report the implementation, dosimetric results of and early experiences with stereotactic accelerated partial breast irradiation (SAPBI) following breast conserving surgery (BCS) for postmenopausal low-risk St I-II invasive breast cancer (IBC) patients. Between November 2018 and August 2019, 27 patients were registered in our phase II prospective study. SAPBI was performed with Cyber-Knife (CK) M6 machine, in 4 daily fractions of 6.25 Gy to a total dose of 25 Gy. Respiratory movements were followed with implanted gold markers and Synchrony system. Corrections for patient displacement and respiratory movement during treatment were performed with the robotic arm. Early side effects, cosmetic results, and dosimetric parameters were assessed. The average volume of the surgical cavity, clinical target volume (CTV), and planning target volume (PTV_EVAL) were 8.1 cm3 (range: 1.75–27.3 cm3), 55.3 cm3 (range: 26.2–103.5 cm3), and 75.7 cm3 (range: 40–135.4 cm3), respectively. The mean value of the PTV_eval/whole breast volume ratio was 0.09 (range: 0.04–0.19). No grade 2 or worst acute side-effect was detected. Grade 1 (G1) erythema occurred in 6 (22.2%) patients, while G1 oedema was reported by 3 (11.1%) cases. G1 pain was observed in 1 (3.4%) patient. Cosmetic result were excellent in 17 (62.9%) and good in 10 (37.1%) patients. SAPBI with CK is a suitable and practicable technique for the delivery of APBI after BCS for low-risk, St. I-II. IBC. Our early findings are encouraging, CK-SAPBI performed with four daily fractions is convenient and perfectly tolerated by the patients.
C1 [Meszaros, Norbert] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Smanyko, Viktor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Major, Tibor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Stelczer, Gabor] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Janvary, Zsolt Levente] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Kovacs, Eszter] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Baheri, Maria] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Zaka, Zoltan] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Pukancsik, David] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Takacsi-Nagy, Zoltan] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
[Polgar, Csaba] National Institute of Oncology, Center of Radiotherapy, Rath Gyorgy u. 7-9, H-1122 Budapest, Hungary.
RP Meszaros, N (reprint author), National Institute of Oncology, Center of Radiotherapy, H-1122 Budapest, Hungary.
EM meszarosnorbert@oncol.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2307
EP 2313
DI 10.1007/s12253-020-00821-3
PG 7
ER
PT J
AU Kengkarn, S
Petmitr, S
Boonyuen, U
Reamtong, O
Poomsawat, S
Sanguansin, S
AF Kengkarn, Sudaporn
Petmitr, Songsak
Boonyuen, Usa
Reamtong, Onrapak
Poomsawat, Sopee
Sanguansin, Sirima
TI Identification of Novel Candidate Biomarkers for Oral Squamous Cell Carcinoma Based on Whole Gene Expression Profiling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Gene expression profile; Biomarker; PI3; KRT17
ID Oral squamous cell carcinoma; Gene expression profile; Biomarker; PI3; KRT17
AB This study aimed to determine the whole gene expression profiles and to ascertain potential biomarkers for 22 oral squamous cell carcinoma (OSCC) among Thai patients using the Illumina Human HT-12, V4.0 Expression BeadChip array. Result indicated 2,724 differential expressed genes composed of 1,560 up-regulated and 1,164 down-regulated genes (unpaired t-test, p-value <0.05; fold change ≥2.0 and ≤2.0). The top 9 up-regulated genes were validated in 39 OSCC cases using TaqMan real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. Among these, the up-regulation of peptidase inhibitor 3 (PI3) and keratin 17 (KRT17) genes was harbored in all 39 OSCC patients (100%). Likewise, statistical analysis indicated that gene expression in 8 selective genes including keratin 16 (KRT16), keratin 14 (KRT14), keratinocyte differentiation-associated protein (KRTDAP), keratin 6B (KRT6B), PI3, S100 calcium binding protein A7 (S100A7), stratifin (SFN) and keratin 5 (KRT5) was significantly associated with well differentiated OSCC (p-value <0.05). Moreover, high level of KRT17 protein was significantly associated with well differentiated OSCC compared to moderately OSCC (p-value = 0.041). Notably, using nested-PCR analysis indicated all OSCC cases in this study were HPV-free. Especially, KRTDAP, PI3, SFN mRNA expression were first reported among patients with OSCC. Conclusion, the whole transcript expression study and TaqMan real-time qRT-PCR assay were relevant regarding the increase in gene expression in OSCC. In addition, the upregulation of PI3 and KRT17 might constitute potential candidate molecular biomarkers to diagnose patients with OSCC.
C1 [Kengkarn, Sudaporn] Mahidol University, Faculty of Tropical Medicine, Department of Molecular Tropical Medicine & GeneticsBangkok, Thailand.
[Petmitr, Songsak] Mahidol University, Faculty of Tropical Medicine, Department of Molecular Tropical Medicine & GeneticsBangkok, Thailand.
[Boonyuen, Usa] Mahidol University, Faculty of Tropical Medicine, Department of Molecular Tropical Medicine & GeneticsBangkok, Thailand.
[Reamtong, Onrapak] Mahidol University, Faculty of Tropical Medicine, Department of Molecular Tropical Medicine & GeneticsBangkok, Thailand.
[Poomsawat, Sopee] Mahidol University, Faculty of Dentistry, Department of Oral and Maxillofacial PathologyBangkok, Thailand.
[Sanguansin, Sirima] Mahidol University, Faculty of Dentistry, Department of Oral BiologyBangkok, Thailand.
RP Sanguansin, S (reprint author), Mahidol University, Faculty of Dentistry, Department of Oral Biology, Bangkok, Thailand.
EM sirima.san@mahidol.ac.th
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2315
EP 2325
DI 10.1007/s12253-020-00828-w
PG 11
ER
PT J
AU Cheng, Z
Shu, H
Cui, Y
Zhang, Q
Zhao, B
Pan, D
Chao, Q
Wang, D
AF Cheng, Zhe
Shu, Hansheng
Cui, Ying
Zhang, Qiujian
Zhao, Biao
Pan, Didi
Chao, Qing
Wang, Dawei
TI MiR-424-5p Inhibits Proliferation, Invasion and Promotes Apoptosis and Predicts Good Prognosis in Glioma by Directly Targeting BFAR
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Glioma; Bifunctional apoptosis regulator; Prognosis; MicroRNA
ID Glioma; Bifunctional apoptosis regulator; Prognosis; MicroRNA
AB The biological function of miRNA (miR)-424-5p in glioma has not been clarified. This study was to explore the roles of miR- 424-5p/Bifunctional apoptosis regulator (BFAR) axis in glioma. Ninety-six pairs of human glioma tissues and their adjacent noncancer tissues were collected. The levels of BFAR and miR-424-5p were detected by quantitative polymerase chain reaction (qPCR) in glioma tissues and cell lines. Moreover, the biological roles of miR-424-5p and BFAR in glioma cells were assessed. We found a miR-424-5p binding site in the 3’UTR of BFAR by using TargetScan 7.2 online database. ThemiR-424-5p level was dramatically decreased in glioma tissues and cell lines, and the BFAR expression was significantly increased. The BFAR expression was negatively related to the miR-424-5p level in glioma tissues. Compared to patients with high miR-424-5p levels in glioma tissues, patients with low miR-424-5p levels had significantly lower survival rate (χ2 = 13.728 and P < 0.001). Compared to patients with high BFAR levels in glioma tissues, patients with low BFAR levels had significantly higher survival rate (χ2 = 5.516 and P = 0.027). Furthermore, up-regulation of miR-424-5p obviously restrained glioma cells proliferation and invasion, and promoted apoptosis. Besides, knockdown of BFAR also could markedly inhibit the proliferation and invasion, and promote apoptosis. Finally, overexpression of BFAR in glioma cells partially reversed the inhibited effects of miR-424-5p mimic. Knockdown of miR-424-5p restrained glioma cell apoptosis and promoted invasion and proliferation via regulation of BFAR.
C1 [Cheng, Zhe] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Shu, Hansheng] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Cui, Ying] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Zhang, Qiujian] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Zhao, Biao] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Pan, Didi] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Chao, Qing] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
[Wang, Dawei] The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, No. 220 Hongye Road, West of Longzi LakeBengbu, Anhui Province, China.
RP Wang, D (reprint author), The Second Affiliated Hospital of Bengbu Medical College, Department of Neurosurgery, Bengbu, China.
EM yu_geng16@yeah.net
CR Chen J, Wu X, Xing Z, Ma C, Xiong W, Zhu X, He X, 2018, FOXG1 expression is elevated in Glioma and inhibits Glioma cell apoptosis. J Cancer 9:778–783
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2327
EP 2335
DI 10.1007/s12253-020-00831-1
PG 9
ER
PT J
AU Bartu, M
Hojny, J
Hajkova, N
Michalkova, R
Krkavcova, E
Simon, K
Fryba, V
Struzinska, I
Nemejcova, K
Dundr, P
AF Bartu, Michaela
Hojny, Jan
Hajkova, Nikola
Michalkova, Romana
Krkavcova, Eva
Simon, Karol
Fryba, Vladimir
Struzinska, Ivana
Nemejcova, Kristyna
Dundr, Pavel
TI Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon; Adenoma; HNF-1-beta; Immunohistochemistry; Mutation analysis; Methylation
ID Colon; Adenoma; HNF-1-beta; Immunohistochemistry; Mutation analysis; Methylation
AB Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. Themutation analysis revealed three somaticmutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.
C1 [Bartu, Michaela] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Hojny, Jan] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Hajkova, Nikola] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Michalkova, Romana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Krkavcova, Eva] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Simon, Karol] Charles University, 1st Faculty of Medicine and General Teaching Hospital, 12800 Prague, Czech Republic.
[Fryba, Vladimir] Charles University and General University Hospital, First Faculty of Medicine, 1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology, 12808 Prague, Czech Republic.
[Struzinska, Ivana] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Nemejcova, Kristyna] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
[Dundr, Pavel] Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, Studnickova 2, 12800 Prague, Czech Republic.
RP Dundr, P (reprint author), Charles University, 1st Faculty of Medicine and General Teaching Hospital, Department of Pathology, 12800 Prague, Czech Republic.
EM Pavel.Dundr@vfn.cz
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2337
EP 2350
DI 10.1007/s12253-020-00830-2
PG 14
ER
PT J
AU Khatib, G
Gulec, KU
Guzel, BA
Bagir, E
Paydas, S
Vardar, AM
AF Khatib, Ghanim
Gulec, Kucukgoz Umran
Guzel, Baris Ahmet
Bagir, Emine
Paydas, Semra
Vardar, Ali Mehmet
TI Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endometrioid endometrial carcinoma; FIGOgrade; Oncologic outcomes; Interobserver reproducibility
ID Endometrioid endometrial carcinoma; FIGOgrade; Oncologic outcomes; Interobserver reproducibility
AB Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients’ records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups’ characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan–Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients’ mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.
C1 [Khatib, Ghanim] Cukurova University, Faculty of Medicine, Department of Obstetrics and Gynecology, 01330 Adana, Turkey.
[Gulec, Kucukgoz Umran] Cukurova University, Faculty of Medicine, Department of Obstetrics and Gynecology, 01330 Adana, Turkey.
[Guzel, Baris Ahmet] Cukurova University, Faculty of Medicine, Department of Obstetrics and Gynecology, 01330 Adana, Turkey.
[Bagir, Emine] Cukurova University, School of Medicine, Pathology Department, 01330 Adana, Turkey.
[Paydas, Semra] Cukurova University, Faculty of Medicine, Department of Medical Oncology, 01330 Adana, Turkey.
[Vardar, Ali Mehmet] Cukurova University, Faculty of Medicine, Department of Obstetrics and Gynecology, 01330 Adana, Turkey.
RP Khatib, G (reprint author), Cukurova University, Faculty of Medicine, Department of Obstetrics and Gynecology, 01330 Adana, Turkey.
EM ghanim.khatib@gmail.com
CR Clarke BA, Gilks CB, 2010, Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol 63:410–415
Tanaka K, Kobayashi Y, Sugiyama J et al, 2017, Histologic grade and peritoneal cytology as prognostic factors in type 1 endometrial cancer. Int J Clin Oncol 22:533–540
Alkushi A, Abdul-Rahman ZH, Lim P et al, 2005, Description of a novel system for grading of endometrial carcinoma and comparison with existing grading systems. Am J Surg Pathol 29:295–304
Scholten AN, Creutzberg CL, Noordijk EM, SmitVT, 2002, Longterm outcome in endometrial carcinoma favors a two- instead of a three-tiered grading system. Int J Radiat Oncol Biol Phys 52:1067– 1074
Bilgin T, Ozuysal S, Ozan H, 2005, A comparison of three histological grading systems in endometrial cancer. Arch Gynecol Obstet 272:23–25
Colombo N, Creutzberg C, Aman t Fet al., 2016, ESMO-ESGOESTRO consensus conference on endometrial Cancer: diagnosis, treatment and follow-up. Int J Gynecol Cancer 26:2–30
Jones HW 3rd, 1999, The importance of grading in endometrial cancer. Gynecol Oncol 74:1–2
Creasman WT, Odicino F, Maisonneuve P et al, 2006, Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological Cancer. Int J Gynaecol Obstet 95(Suppl 1): S105–S143
Binder PS, Mutch DG, 2014, Update on prognostic markers for endometrial cancer. Womens Health, Lond, 10:277–288
Lax SF, Kurman RJ, Pizer ES et al, 2000, A binary architectural grading systemfor uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis. Am J Surg Pathol 24:1201–1208
Scholten AN, Smit VT, Beerman H et al, 2004, Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma. Cancer 100:764–772
Creutzberg CL, van PuttenWL, Koper PC et al, 2000, Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC study group. Post operative radiation therapy in endometrial carcinoma. Lancet 355:1404–1411
Taylor RR, Zeller J, Lieberman RW, O'Connor DM, 1999, An analysis of two versus three grades for endometrial carcinoma. Gynecol Oncol 74:3–6
Gemer O, Uriev L, VoldarskyMet al, 2009, The reproducibility of histological parameters employed in the novel binary grading systems of endometrial cancer. Eur J Surg Oncol 35:247–251
Kapucuoglu N, Bulbul D, Tulunay G, Temel MA, 2008, Reproducibility of grading systems for endometrial endometrioid carcinoma and their relationwith pathologic prognostic parameters. Int J Gynecol Cancer 18:790–796
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2351
EP 2356
DI 10.1007/s12253-020-00836-w
PG 6
ER
PT J
AU Kravchick, S
Cherniavsky, E
Peled, R
Cytron, Sh
Verhovsky, G
AF Kravchick, Sergey
Cherniavsky, Eugenia
Peled, Ronit
Cytron, Shmuel
Verhovsky, Guy
TI Power Doppler Sonography (PDS) and Modified TRUS Systematic Biopsies – Can this Combination Adequately ReplaceMultiparametric Prostate Magnetic Resonance Imaging (mp-MRI) in Candidates for Re Biopsies Who cannot Undergo mp-MRI
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Targeted biopsy; Diagnostic; Imaging
ID Prostate cancer; Targeted biopsy; Diagnostic; Imaging
AB The MRI targeted biopsy (MRI-TBx) may increase the detection rate of clinically significant cancer (csPCa) in candidates for rebiopsy. However, there will be several patients in whom MRI is contraindicated. In this retrospective study we assessed the ability of combination of PDS guided biopsies (PDS-TBx) and modified SBx to substitute MRI-TBx. 154 men with persistently elevated PSA were referred for re-biopsy. Our protocol included a combination of MRI-TBx, DPS-TBx and modified SBx with additional biopsies from anterior lateral horns and anterior aspects of apex. MRI findings were defined as suspicious lesions (MRI-SL) and highly suspicious lesions (MRI-HL), based on PIRADS scale. In 40 patients csPCa was detected.While,MRI diagnosed csPCa in 36 patients (23%, n-36/154): 25% and 92% of biopsies targeted to theMRI- SL and MRI-HSL confirmed csPCa. Thirty-eight PDS hypervascular areas were found, while csPCa was diagnosed in 84% of these lesions, or in 28 patients (18%, n-28/154). SBx detected csPCa in 34 cores or in 21 patients (13%, n – 21/154). SBx missed cancers in the in the anterior aspect of middle gland. Combination of PDSTBx + SBx detected csPCa in 35 (88% of csPCa) patients. Strongest predictors for the csPCa presence were MRI-HSL, PDS’ lesions and biopsies from anterior aspect that included apex, mid gland and anterior lateral horns (p < 0.001 and p-0.008, respectively). The combination of PDS-TBx + SBx may miss 15% of csPCa detected by MRI. However, it can detect additional 10%of csPCa that were missed by MRI. To improve the accuracy of this combination, the anterior aspect of middle gland should be also included in the modified SBx. These changes in combination can make it helpful in candidates for re-biopsy who cannot undergo MRI.
C1 [Kravchick, Sergey] Upstate Medical University, Department of UrologySyracuse, NY, USA.
[Cherniavsky, Eugenia] Barzilay Medical Center, Department of RadiologyAshkelon, Israel.
[Peled, Ronit] Ben Gurion University, Epidemiology and StatisticsBeer-Sheva, Israel.
[Cytron, Shmuel] Barzialy Medical Center, Urology DepartmentAshkelon, Israel.
[Verhovsky, Guy] Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of UrologyTel Aviv, Israel.
RP Verhovsky, G (reprint author), Hasharon Hospital, Rabin Medical Center, Petah-Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Department of Urology, Tel Aviv, Israel.
EM guy.verchovsky@gmail.com
CR Welch HG, Fisher ES, Gottlieb DJ, Barry MJ, 2007, Detection of prostate cancer via biopsy in the Medicare–SEER population during the PSA era. J Natl Cancer Inst 99:1395–1400
Moore CM, Robertson NL, Arsanious N, Middleton T, Villers A, Klotz L, Taneja SS, Emberton M, 2013, Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol 63:125–140
Sonn GA, Chang E, Natarajan S et al, 2014, Value of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigen. Eur Urol 65:809–815
Wysock JS, Rosenkrantz AB, Huang WC et al, 2013, A prospective, blinded comparison of magnetic resonance, MR, imagingultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial. Eur Urol 66: 343–351
Salami SS, Ben-Levi E, YaskivO, Ryniker L, Turkbey B,Kavoussi LR, Villani R, Rastinehad AR, 2015, In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy? BJU Int 115:562–570
Schoots IG, Roobol MJ, Nieboer D, Chris H, Bangma CH, Steyerberg EW, Hunink MG, 2015, Magnetic resonance imaging–targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta- analysis. Eur Urol 68:438–450
Le JD, Stephenson S, Brugger M et al, 2014, MRI-ultrasound fusion biopsy for prediction of final prostate pathology. J Urol 192: 1367–1373
Mathur S, O'MalleyME,Ghai S, Jhaveri K, Sreeharsha B,Margolis M, Zhong L, Maan H, Toi A, 2019, Correlation of 3T multiparametric prostate MRI using prostate imaging reporting and data system, PIRADS, version 2 with biopsy as reference standard. Abdom Radiol, NY, 44(1):252–258
Puech P, Rouviere O, Renard-Penna R et al, 2013, Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsyprospective multicenter study. Radiology 268:461–469
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Chow GV, Nazarian S, 2014, MRI for patients with cardiac implantable electrical devices. Cardiol Clin 32:299–304
Bastide C, Lechevallier E, Eghazarian C, Ortega JC, Coulange C, 2003, Tolerance of pain during transrectal ultrasound-guided biopsy of the prostate: risk factors. Prostate Cancer Prostatic Dis 6: 239–241
Kravchick S, Yoffe B, Cytron S, 2007, Modified perianal/ pericapsular anesthesia for transrectal biopsy of prostate in patients with anal rectal problems. Urology 69(1):139–141
Gold SA, Hale GR, Bloom JB, Smith CP, Rayn KN, Valera V, Wood BJ, Choyke PL, Turkbey B, Pinto PA, 2019, Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer? World J Urol 37(2):235–241
Takahashi S, Yamada Y, Homma Y, Horie S, Hosaka Y, Kitamura T, 2002, Power Doppler ultrasonography-directed prostate biopsy in men with elevated serum PSA levels: an evaluation of the clinical utility and limitations. Urology. 60(2):248–252
Eisenberg ML, Cowan JE, Carroll PR, Shinohara K, 2010, The adjunctive use of power Doppler imaging in the preoperative assessment of prostate cancer. BJU Int 105:1237–1241
Remzi M, DobrovitsM, Reissigl A, Ravery V,WaldertM,Wiunig C, Fong YK, Djavan B, European Society for Oncological Urology, ESOU,, 2004, Can power Doppler enhanced transrectal ultrasound guided biopsy improve prostate cancer detection on first and repeat prostate biopsy? Eur Urol 46(4):451–456
Wright JL, EllisWJ, 2006, Improved prostate cancer detection with anterior apical prostate biopsies. Urol Oncol 24:492–495
DjavanB ZAR, Remzi M, Ghawidel K, Basharkhah A, Schulman CC et al, 2000, Optimal predictors of prostate cancer in repeat prostate biopsy: a prospective study of 1051 men. J Urol 163: 1144–1148
Kim M, Choi SK, Park M, Shim M, Song C, Jeong IG, Hong JH, Kim CS, Ahn H, 2016, Characteristics of anterior located prostate cancer and usefulness of multiparametric magnetic resonance imaging for diagnosis. J Urol 196(2):367–373
Takashima R, Egawa S, Kuwao S, Baba S, 2002, Anterior distribution of Stage T1c nonpalpable tumors in radical prostatectomy specimens. Urology 59(5):692–697
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2357
EP 2361
DI 10.1007/s12253-020-00824-0
PG 5
ER
PT J
AU Guleria, P
Kumar, S
Malik, SP
Jain, D
AF Guleria, Prerna
Kumar, Sunil
Malik, Singh Prabhat
Jain, Deepali
TI PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pulmonary high grade neuroendocrine tumors; PD-L1; SP263; Immunotherapy; Small cell lung carcinoma
ID Pulmonary high grade neuroendocrine tumors; PD-L1; SP263; Immunotherapy; Small cell lung carcinoma
AB High-grade neuroendocrine tumors (HGNET) have distinctive tumor biology/behaviour. Newer modalities of treatment (immunotherapy) for them have been included in recent NCCN guidelines. Detection of programmed death receptor-ligand 1 (PD-L1) expression by immunohistochemistry have made easy identification of patients eligible for immunotherapy. We aimed to ascertain expression of PD-L1 on small cell and large cell neuroendocrine carcinomas of lung and review existing literature. Eighty-five cases of HGNET lung (primary/metastatic), were retrieved and reviewed. Immunostaining for PD-L1 using clone SP263 was done. Any amount/intensity of membranous staining of > = 1% tumor cells was cut-off for positivity. Previously published studies using Google and/Pubmed search engines were reviewed. Of 85 cases, 70 were small-cell lung cancer (SCLC), 11 large-cell neuroendocrine carcinoma (LCNEC) and 4 combined SCLC. Median age was 46.5 years with male preponderance. No PD-L1 expression was seen in 91.6% cases. The 7 positive cases were 4 LCNEC, 2 SCLC and 1 combined SCLC. The percentage positivity varied from 1–100%; lower percentage positivity was seen in SCLC. PD-L1 expression on immune cells was seen in 31.3%cases. Sixteen studies evaluating 1992 NETwere found; E1L3N PD-L1 clone was commonly used clone. PDL1 positivity was associated with better prognosis in most studies. There are only a few studies available in literature related to PDL1 expression in high grade neuroendocrine carcinomas of lung. In general, PD-L1 positivity is highly variable and seen in lower percentage of these tumors. With the recent approval of immunotherapy, biomarkers other than PD-L1 should also be investigated in these tumors.
C1 [Guleria, Prerna] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
[Kumar, Sunil] All India Institute of Medical Sciences, Dr BRA Institute-Rotary Cancer Hospital, Department of Surgical Oncology, 110029 New Delhi, India.
[Malik, Singh Prabhat] All India Institute of Medical Sciences, Dr BRA Institute-Rotary Cancer Hospital, Department of Medical Oncology, 110029 New Delhi, India.
[Jain, Deepali] All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
RP Jain, D (reprint author), All India Institute of Medical Sciences, Department of Pathology, 110029 New Delhi, India.
EM deepalijain76@gmail.com
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Tang J, Yu JX, Hubbard-Lucey VM, Neftelinov ST, Hodge JP, Lin Y. Trial watch: the clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nat Rev Drug Discov 2018:854–855
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Inamura K. Update on immunohistochemistry for the diagnosis of lung cancer. Cancers, Basel, 2018:1–15
Tsao MS, Kerr KM, Dacic S, Yatabe Y, Hirsch FR, 2017, IASLC atlas of PD-L1 immunohistochemistry testing in lung cancer. Editorial Rx Press, North Fort Myers
Schultheis AM, Scheel AH, Ozretic L, George J, Thomas RK, Hagemann T, Zander T, Wolf J, Buettner R. PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer 2015:421–426
George J, Fernandez-Cuesta L, Walter V, Hayes N. Comparative analysis of small cell lung cancer and other pulmonary neuroendocrine tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16–20; New Orleans, LA. Philadelphia, PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 122
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2363
EP 2370
DI 10.1007/s12253-020-00832-0
PG 8
ER
PT J
AU Ye, L
Ardakani, MN
Thomas, C
Spilsbury, K
Leslie, C
Amanuel, B
Millward, M
AF Ye, Linda
Ardakani, Mesbah Nima
Thomas, Carla
Spilsbury, Katrina
Leslie, Connull
Amanuel, Benhur
Millward, Michael
TI Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) Resistance Mutation in Pre-treatment Non-small Cell Lung Carcinomas Harboring Activating EGFR Mutations and Correlation with Clinical Outcomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Activating EGFR mutation; T790M mutation; Digital PCR; Tyrosine kinase inhibitor; Mutation allele frequency
ID Activating EGFR mutation; T790M mutation; Digital PCR; Tyrosine kinase inhibitor; Mutation allele frequency
AB Increasing evidence points to the presence of low-level de novo T790Mmutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations. T790M was detected in 42 of 109 pre-treatment samples (38.5%). Median variant allele frequency was 0.14%(range 0.02–28.5%). Overall response rate to first generation EGFR tyrosine kinase inhibitors (TKI) was 67% regardless of T790Mstatus. The median progression free survival was 10.7 (IQR 5.6–19.9) versus 6.7 (IQR 3.5–20.8) months in T790Mnegative and positive patients respectively. T790M positivity correlated with increased rate of early disease progression. It also correlated with increased mortality (HR 3.1 95%CI 1.2–8.1, p = 0.022) in patients who did not respond to TKI treatment. We detected a significant rate of low-level pre-treatment T790M mutations in NSCLC using highly sensitive dPCR. Low-level pre-treatment T790M did not impact treatment response rate or overall survival, but was associated with increased rate of early progression on TKI therapy.
C1 [Ye, Linda] Sir Charles Gairdner Hospital, Department of Medical OncologyPerth, Western Australia, Australia.
[Ardakani, Mesbah Nima] The University of Western Australia, School of Pathology and Laboratory MedicineCrawley, Western Australia, Australia.
[Thomas, Carla] The University of Western Australia, School of Pathology and Laboratory MedicineCrawley, Western Australia, Australia.
[Spilsbury, Katrina] The University of Notre Dame Australia, Institute for Health ResearchPerth, Western Australia, Australia.
[Leslie, Connull] The University of Western Australia, School of Pathology and Laboratory MedicineCrawley, Western Australia, Australia.
[Amanuel, Benhur] The University of Western Australia, School of Pathology and Laboratory MedicineCrawley, Western Australia, Australia.
[Millward, Michael] Sir Charles Gairdner Hospital, Department of Medical OncologyPerth, Western Australia, Australia.
RP Ardakani, MN (reprint author), The University of Western Australia, School of Pathology and Laboratory Medicine, Crawley, Australia.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2371
EP 2379
DI 10.1007/s12253-020-00833-z
PG 9
ER
PT J
AU Gibo, T
Yamada, Shi
Kawamoto, M
Uehara, T
Kurita, H
AF Gibo, Takahiko
Yamada, Shin-ichi
Kawamoto, Makiko
Uehara, Takeshi
Kurita, Hiroshi
TI Immunohistochemical Investigation of Predictive Biomarkers for Mandibular Bone Invasion in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Oral squamous cell carcinoma; Mandible; Bone invasion; ɑ-SMA; Predictive marker
ID Oral squamous cell carcinoma; Mandible; Bone invasion; ɑ-SMA; Predictive marker
AB The accurate preoperative determination of the extent of mandibular resection remains a challenge for the surgeons. The purpose of the present study was to immunohistochemically investigate predictive markers for histological bone invasion of oral squamous cell carcinoma (OSCC). The medical records of primary OSCC patients with mandibular bone contact in preoperative computed tomography scans between January 2003 and December 2017 were retrospectively reviewed and an immunohistochemical investigation was performed. Forty-five OSCC patients with mandibular bone contact radiographically were included in this study. Histopathologically, infiltrative bone invasion was observed in 19 patients (42.2%) and compressive bone invasion in 15 (33.3%). A correlation was noted between the histological pattern of bone invasion and mode of invasion (chi-squared test, p < 0.05). At the tumor surface, a correlation was observed between the expression of IL-6 and bone invasion (theWilcoxon test, p < 0.05), although the expressionwas soweak. At the bone contact area, the expression of both ɑ-SMAand OPG correlated with infiltrative bone invasion (ɑ-SMA; the Wilcoxon test, p < 0.05, OPG; p < 0.05). These results suggest that predictive markers for aggressive (infiltrative) bone invasion in OSCC patients with a higher mode of invasion are the expression of ɑ-SMA and OPG.
C1 [Gibo, Takahiko] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Yamada, Shin-ichi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Kawamoto, Makiko] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Uehara, Takeshi] Shinshu University School of Medicine, Department of Laboratory Medicine, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
[Kurita, Hiroshi] Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 3-1-1, Asahi, 390-8621 Matsumoto, Japan.
RP Yamada, Shi (reprint author), Shinshu University, School of Medicine, Department of Dentistry and Oral Surgery, 390-8621 Matsumoto, Japan.
EM yshinshin@shinshu-u.ac.jp
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Radisky DC, Kenny PA, Bissell MJ, 2007, Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 101:830–839
Saadi A, Shannon NB, Lao-Sirieix P, O'Donovan M, Walker E, Clemons NJ, Hardwick JS, Zhang C, Das M, Save V, Novelli M, Balkwill F, Fitzgerald RC, 2010, Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Proc Natl Acad Sci U S A 107:2177–2182
VeredM, Dayan D, Yahalom R, Dobriyan A, Barshack I, Bello IO, Kantola S, Salo T, 2010, Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma. Int J Cancer 127:1356–1362
Marsh D, Suchak K, Moutasim KA, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette SM, Weinreb PH, Chester KA, Chana JS, Marshall JF, Hart IR, Hackshaw AK, Piper K, Thomas GJ, 2011, Stromal features are predictive of disease mortality in oral cancer patients. J Pathol 223:470–481
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Qiao B, Johnson NW, Gao J, 2010, Epithelial-mesenchymal transition in oral squamous cell carcinoma triggered by transforming growth factor-beta1 is snail family-dependent and correlates with matrix metalloproteinase-2 and -9 expressions. Int J Oncol 37:663– 668
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2381
EP 2389
DI 10.1007/s12253-020-00826-y
PG 9
ER
PT J
AU Pal, D
Szilagyi, B
Berczeli, M
Szalay, ICs
Sardy, B
Olah, Z
Szekely, T
Racz, G
Banga, P
Czinege, Zs
Sotonyi, P
AF Pal, Daniel
Szilagyi, Brigitta
Berczeli, Marton
Szalay, Imre Csaba
Sardy, Balazs
Olah, Zoltan
Szekely, Tamas
Racz, Gergely
Banga, Peter
Czinege, Zsofia
Sotonyi, Peter
TI Ruptured Aortic Aneurysm and Dissection Related Death: an Autopsy Database Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Acute aortic syndrome; Aortic dissection; Aortic aneurysm; Autopsy; Rupture; Bl
ID Acute aortic syndrome; Aortic dissection; Aortic aneurysm; Autopsy; Rupture; Bl
AB Acute aortic catastrophes (AAC), mainly ruptured aneurysms and dissections, lead all other vascular conditions in morbidity and mortality, even if intervention occurs. The aim of our study was to give a descriptive overview of the demographic and pathological characteristics of AAC. Between 1994 and 2013, 80,469 autopsies were performed at Semmelweis University hospitals in Budapest. After collecting the autopsy reports we were able to create the AAC database upon which we conducted our analysis. We found 567 cases of AAC. The cause of death in 120 of them was classified as a non-ruptured aorta with malperfusion or distal embolization. Of the remaining 447 cases, in 305 the cause of death was a ruptured aortic aneurysm (rAA), and in 142 it was a ruptured aortic dissection (rAD). The distribution of rAA cases was 34.4% thoracal, 4.3% thoracoabdominal, and 61.3% abdominal. We found female dominance where the rAA was thoracal. In rAD cases, 84% were Stanford A and 16% Stanford B type. In both groups we found different pathological distributions. In the prehospital group, the number of thoracal ruptures was considerable. 88% of the patients with Stanford A dissection died in the prehospital or perioperative period. The most progressive AACs were ruptures of intrapericardial aneurysms and Stanford A dissections., however survival rate can be elevated by using rapid imaging examination and immediate surgical intervention. We want to highlight that our study contains such gender differences, which are worth to be taken into consideration.
C1 [Pal, Daniel] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Szilagyi, Brigitta] Budapest University of Technology and Economics, Institute of Mathematics, Department of GeometryBudapest, Hungary.
[Berczeli, Marton] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Szalay, Imre Csaba] Semmelweis University, Department of Cardiovascular SurgeryBudapest, Hungary.
[Sardy, Balazs] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Olah, Zoltan] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Szekely, Tamas] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Racz, Gergely] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Banga, Peter] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Czinege, Zsofia] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
[Sotonyi, Peter] Semmelweis University, Department of Cardiovascular Surgery, Varosmajor u. 68, 1122 Budapest, Hungary.
RP Sotonyi, P (reprint author), Semmelweis University, Department of Cardiovascular Surgery, 1122 Budapest, Hungary.
EM sotonyi@hotmail.com
CR Deaths in reference year, in Hungary, 1995–2015,, 2016, Hungarian Central Statistical Office
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2391
EP 2399
DI 10.1007/s12253-020-00835-x
PG 9
ER
PT J
AU Kontsek, E
Pesti, A
Bjornstedt, M
Uveges,
Szabo, E
Garay, T
Gordon, P
Gergely, Sz
Kiss, A
AF Kontsek, Endre
Pesti, Adrian
Bjornstedt, Mikael
Uveges, T.
Szabo, Edina
Garay, Tamas
Gordon, Peter
Gergely, Szilveszter
Kiss, Andras
TI Mid-Infrared Imaging Is Able to Characterize and Separate Cancer Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cancer; FT-IR; Fingerprint region; Transflectance
ID Cancer; FT-IR; Fingerprint region; Transflectance
AB Malignancies are still responsible for a large share of lethalities. Macroscopical evaluation of the surgical resection margins is uncertain. Big data based imaging approaches have emerged in the recent decade (mass spectrometry, two-photon microscopy, infrared and Raman spectroscopy). Indocianine green labelled MS is the most common approach, however, label free midinfrared imaging is more promising for future practical application. We aimed to identify and separate different transformed (A-375, HT-29) and non-transformed (CCD986SK) cell lines by a label-free infrared spectroscopy method. Our approach applied a novel set-up for label-free mid-infrared range classificationmethod. Transflection spectroscopywas used on aluminium coated glass slides. Both whole range spectra (4000–648 cm−1) and hypersensitive fingerprint regions (1800–648 cm−1) were tested on the imaged areas of cell lines fixed in ethanol. Non-cell spectra were possible to be excluded based on mean transmission values being above 90%. Feasibility of a mean transmission based spectra filtering method with principal component analysis and linear discriminant analysis was shown to separate cell lines representing different tissue types. Fingerprint region resulted the best separation of cell lines spectra with accuracy of 99.84% at 70–75 mean transmittance range. Our approach in vitro was able to separate unique cell lines representing different tissues of origin. Proper data handling and spectra processing are key steps to achieve the adaptation of this dye-free technique for intraoperative surgery. Further studies are urgently needed to test this novel, marker-free approach.
C1 [Kontsek, Endre] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Pesti, Adrian] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Bjornstedt, Mikael] Karolinska University, Department of PathologyStockholm, Sweden.
[Uveges, T.] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food ScienceBudapest, Hungary.
[Szabo, Edina] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food ScienceBudapest, Hungary.
[Garay, Tamas] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Gordon, Peter] Budapest University of Technology and Economics, Department of Electronics TechnologyBudapest, Hungary.
[Gergely, Szilveszter] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food ScienceBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kontsek, E (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
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Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden G, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P,Klauschen F,Watson PH, Nelson BH, Criscitiello C, O'Toole S, Larsimont D, deWind R, Curigliano G, Andre F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB, 2017, Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the international Immunooncology biomarkers working group: part 1: assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research. Adv Anat Pathol 24(5):235–251. , DOI 10.1097/PAP.0000000000000162
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2401
EP 2407
DI 10.1007/s12253-020-00825-z
PG 7
ER
PT J
AU Kotarac, N
Dobrijevic, Z
Matijasevic, S
Savic-Pavicevic, D
Brajuskovic, G
AF Kotarac, Nevena
Dobrijevic, Zorana
Matijasevic, Suzana
Savic-Pavicevic, Dusanka
Brajuskovic, Goran
TI Association of KLK3, VAMP8 and MDM4 Genetic Variants within microRNA Binding Sites with Prostate Cancer: Evidence from Serbian Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE miRSNPs; rs1058205; rs1010; rs4245739; Prostate cancer
ID miRSNPs; rs1058205; rs1010; rs4245739; Prostate cancer
AB A growing number of studies have suggested that genetic variants affecting the micro-RNA- binding mechanisms (miRSNPs) constitute a promising novel class of biomarkers for prostate cancer (PCa) biology. Among the most extensively studied miRSNPs in the context of cancer is the variation rs4245739 in the MDM4 gene, while a recent large-scale analysis revealed significant differences in genotype distributions between aggressive and non-aggressive disease for rs1058205 in KLK3 and rs1010 in VAMP8. In this study, we examined a total of 1083 subjects for these three variants using Taqman® SNP Genotyping Assays. Three hundred and fifty-five samples of peripheral blood were obtained from patients with PCa and 358 samples from patients with benign prostatic hyperplasia (BPH). The control group consisted of 370 healthy volunteers. Comparisons of genotype distributions among PCa and BPH patients, as well as between PCa patients and healthy controls, yielded no evidence of association between the analyzed genetic variants and the risk of developing PCa. However, all three tested genetic variants have shown the association with the parameters of PCa progression. For KLK3 variant rs1058205, minor allele C was found to associate with the lower serum PSA score in PCa patients (PSA > 20 ng/ml vs. PSA < 10 ng/ml comparison, Prec = 0.038; ORrec = 0.20, 95%CI 0.04–1.05). The obtained results point out the potential relevance of the tested genetic variants for the disease aggressiveness assessment.
C1 [Kotarac, Nevena] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Dobrijevic, Zorana] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Matijasevic, Suzana] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Savic-Pavicevic, Dusanka] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
[Brajuskovic, Goran] University in Belgrade, Medical Faculty, Institute for Human GeneticsBelgrade, Serbia.
RP Brajuskovic, G (reprint author), University in Belgrade, Medical Faculty, Institute for Human Genetics, Belgrade, Serbia.
EM brajuskovic@bio.bg.ac.rs
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2409
EP 2423
DI 10.1007/s12253-020-00839-7
PG 15
ER
PT J
TI A Three-microRNA Panel in Serum: Serving as a Potential Diagnostic Biomarker for Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; SerummiRNA; Biomarker; Non-invasive
ID Renal cell carcinoma; SerummiRNA; Biomarker; Non-invasive
AB Purpose: Renal cell carcinoma (RCC) accounts for about 120,000 death each year. Although surgery is a routine treatment, RCC could be fatal if not diagnosed at an early stage. This study aims to search for suitable serum biomarkers and construct a miRNA panel with high diagnostic sensitivity or specificity. Methods: Totally 146 RCC patients and 150 normal control were involved in this three-stage study. Serum expression levels of 30 miRNAs selected from literature were tested by reverse transcription quantitative PCR (RT-qPCR) in the screening stage, the testing stage, and the validation stage. The diagnostic efficiency of miRNAs was evaluated by receiver operating characteristic (ROC) curve and area under curve (AUC) analysis. A panel with the highest diagnostic efficiency was constructed by backward stepwise logistic regression analysis. Additionally, bioinformatics analysis was used to investigate potential biological functions and mechanisms of candidate miRNAs. Results: MiR-224-5p, miR-34b-3p, miR-129-2-3p and miR-182-5p with low to moderate diagnostic ability (AUC = 0.692, 0.778, 0.687 and 0.745, respectively) were selected as candidate miRNAs after the three-stage study. The final diagnostic panel was consisted by miR-224-5p, miR-34b-3p and miR-182-5p with AUC = 0.855. No significance has been found between these four miRNAs and tumor location, Fuhrman Grade and AJCC clinical stages of RCC. Bioinformatic analysis suggested that the three-miRNAs panel may participate in tumorigenesis of RCC by targeting CORO1C. Conclusions: The three-miRNA panel in serum could serve as a non-invasive diagnostic biomarker of RCC.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2425
EP 2434
DI 10.1007/s12253-020-00842-y
PG 10
ER
PT J
TI In Vivo Detection of CTC and CTC Plakoglobin Status Helps Predict Prognosis in Patients with Metastatic Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Circulating tumour cells; CellCollector; Metastatic breast cancer; Plakoglobin; Progression-free survival; Overall survival
ID Circulating tumour cells; CellCollector; Metastatic breast cancer; Plakoglobin; Progression-free survival; Overall survival
AB This study aims to detect the prognostic value of circulating tumour cell (CTC) in patients with metastatic breast cancer. In this study, 38 patients with metastatic breast cancer were enrolled. The in vivo CellCollector® method was used to detect the number of CTC in patients. Single CTC and CTC clusters were counted, and the expression of plakoglobin was also analysed. At baseline, 73.7% (28/38) of the patients were positive for ≥ 1 CTC (range, 1–14 cells). No CTC-like events were observed in the control group. Among the CTC-positive patients, 21.4% (6/28) of patients had CTC clusters, and 42.9% (12/28) of patients had plakoglobin-positive CTC. After chemotherapy, 48.6% (17/35) of the patients were positive for ≥ 1 CTC (range, 1–3 cells), of which 3 patients had CTC clusters, and 35.3% (6/17) had plakoglobin-positive CTC. Additionally, we found that the number of CTC clusters in plakoglobin-positive patients was much greater than that in plakoglobin-negative patients, and the number of CTC was associated with the number of sites of metastases. We also found that patients with ≥ 3 CTC at baseline had shorter progression-free survival (PFS) and overall survival (OS), and pre-chemotherapy CTC detection was associated with PFS (P = 0.0001) and OS (P = 0.0091). CTC plakoglobin expression was associated with PFS (P = 0.02) but not OS (P = 0.22). CTC collected by the in vivo CellCollector method in Chinese patients with metastatic breast cancer have prognostic significance. CTC plakoglobin expression may be associated with CTC clusters, and more in-depth studies are needed.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2435
EP 2442
DI 10.1007/s12253-020-00847-7
PG 8
ER
PT J
AU Sejben, A
Nyari, T
Zombori, T
Cserni, G
AF Sejben, Anita
Nyari, Tibor
Zombori, Tamas
Cserni, Gabor
TI Comparison of Nottingham Prognostic Index, PREDICT and PrognosTILs in Triple Negative Breast Cancer –a Retrospective Cohort Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Triple negative breast cancer; Nottingham Prognostic Index; Predict; Tumor infiltrating lymphocytes; PrognosTILs; Prognosis
ID Triple negative breast cancer; Nottingham Prognostic Index; Predict; Tumor infiltrating lymphocytes; PrognosTILs; Prognosis
AB Triple-negative breast cancer (TNBC) represents a heterogenous subtype of breast cancer with generally poor prognosis. The prediction of its prognosis remains essential to clinicians in their therapeutical decision-making process. The aimof our study was to compare the validity of three multivariable analysis derived prognostic systems, the Nottingham Prognostic Index (NPI), PREDICT and PrognosTILs (a prognosticator including tumor infiltrating lymphocytes, TILs) in a series of TNBCs. Patients operated on with TNBC at the Department of Surgery, Bacs-Kiskun County Teaching Hospital, Kecskemet between 2005 and 2016 were included. Clinical and pathological parameters and follow-up data were collected from medical charts. TILs were assessed retrospectively, following international recommendations. Estimated survivals of PrognosTILs, PREDICT and NPI were recorded and compared with real outcomes. Altogether 136 patients were included in this retrospective study. In univariate Cox analysis, type of surgery, pT, pN, stage, NPI and type of adjuvant therapy were the significant prognostic variables. The multivariate Cox-regression strengthened that NPI is an independent predictor of overall and disease-free survivals in TNBCs. The NPI, PREDICT and PrognosTILs could be compared directly only in a ROC curve analysis: the sensitivities and specificities of these predicting systems are rather similar with area under the curve values falling between 0.7 and 0.8, and NPI having the highest values. Our findings reflect the diverse prognosis of TNBC and highlight the difficulties of predicting its outcome. None of the three multivariable prognosticators is inferior to the others, the NPI can reliably be used for TNBCs.
C1 [Sejben, Anita] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
[Nyari, Tibor] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
RP Sejben, A (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM sejben.anita@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2443
EP 2450
DI 10.1007/s12253-020-00846-8
PG 8
ER
PT J
AU Zombori, T
Sejben, A
Tiszlavicz, L
Cserni, G
Palfoldi, R
Csada, E
Furak, J
AF Zombori, Tamas
Sejben, Anita
Tiszlavicz, Laszlo
Cserni, Gabor
Palfoldi, Regina
Csada, Edit
Furak, Jozsef
TI Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Lung adenocarcinoma; Spread through airspaces (STAS); Architectural grade; Lung sparing surgery; Sublobar resection
ID Lung adenocarcinoma; Spread through airspaces (STAS); Architectural grade; Lung sparing surgery; Sublobar resection
AB The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aimof our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0%vs. 68.4%; 5-y-DFS: 71.1%vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR(OS):2.09; HR(DFS):1.52) and STAS (HR(OS):1.51; HR(DFS):1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.
C1 [Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1., H6725 Szeged, Hungary.
[Sejben, Anita] University of Szeged, Department of Pathology, Allomas u. 1., H6725 Szeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of Pathology, Allomas u. 1., H6725 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1., H6725 Szeged, Hungary.
[Palfoldi, Regina] Csongrad County Hospital of Chest Diseases, Alkotmany u. 36., H6772 Deszk, Hungary.
[Csada, Edit] Csongrad County Hospital of Chest Diseases, Alkotmany u. 36., H6772 Deszk, Hungary.
[Furak, Jozsef] University of Szeged, Department of Surgery, Semmelweis u. 8., H6720 Szeged, Hungary.
RP Zombori, T (reprint author), University of Szeged, Department of Pathology, H6725 Szeged, Hungary.
EM zomtam@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2451
EP 2458
DI 10.1007/s12253-020-00855-7
PG 8
ER
PT J
AU Muraro, E
Vaccher, E
Furlan, C
Fratta, E
Fanetti, G
Fae’, AD
Martorelli, D
Cangemi, M
Polesel, J
Navarria, F
Gobitti, C
Comaro, E
Scaini, Ch
Pratesi, Ch
Zanussi, S
Lupato, V
Grando, G
Giacomarra, V
Sulfaro, S
Barzan, L
Dolcetti, R
Steffan, A
Canzonieri, V
Franchin, G
AF Muraro, Elena
Vaccher, Emanuela
Furlan, Carlo
Fratta, Elisabetta
Fanetti, Giuseppe
Fae’, Antonia Damiana
Martorelli, Debora
Cangemi, Michela
Polesel, Jerry
Navarria, Federico
Gobitti, Carlo
Comaro, Elisa
Scaini, Chiara
Pratesi, Chiara
Zanussi, Stefania
Lupato, Valentina
Grando, Giuseppe
Giacomarra, Vittorio
Sulfaro, Sandro
Barzan, Luigi
Dolcetti, Riccardo
Steffan, Agostino
Canzonieri, Vincenzo
Franchin, Giovanni
TI Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nasopharyngeal carcinoma; Immunosuppression; EBV-specific immunity; Chemoradiotherapy; CD8; FoxP3
ID Nasopharyngeal carcinoma; Immunosuppression; EBV-specific immunity; Chemoradiotherapy; CD8; FoxP3
AB Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.
C1 [Muraro, Elena] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Vaccher, Emanuela] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department ofMedicalOncologyAviano, PN, Italy.
[Furlan, Carlo] General Hospital “San Martino”, Department of Radiation OncologyBelluno, Italy.
[Fratta, Elisabetta] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Fanetti, Giuseppe] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Radiation OncologyAviano, PN, Italy.
[Fae’, Antonia Damiana] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Martorelli, Debora] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Cangemi, Michela] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Polesel, Jerry] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Unit of Cancer EpidemiologyAviano, PN, Italy.
[Navarria, Federico] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Radiation OncologyAviano, PN, Italy.
[Gobitti, Carlo] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Radiation OncologyAviano, PN, Italy.
[Comaro, Elisa] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Scaini, Chiara] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Pratesi, Chiara] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Zanussi, Stefania] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Lupato, Valentina] General Hospital “S. Maria degli Angeli”, Unit of OtolaryngologyPordenone, Italy.
[Grando, Giuseppe] General Hospital “S. Maria degli Angeli”, Unit of OtolaryngologyPordenone, Italy.
[Giacomarra, Vittorio] General Hospital “S. Maria degli Angeli”, Unit of OtolaryngologyPordenone, Italy.
[Sulfaro, Sandro] General Hospital “S. Maria degli Angeli”, Division of PathologyPordenone, Italy.
[Barzan, Luigi] Centro di Riferimento Oncologico di Aviano (CRO) IRCCSAviano, PN, Italy.
[Dolcetti, Riccardo] University of Queensland Diamantina Institute, Translational Research InstituteBrisbane, Australia.
[Steffan, Agostino] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers UnitAviano, PN, Italy.
[Canzonieri, Vincenzo] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Pathology UnitAviano, PN, Italy.
[Franchin, Giovanni] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Radiation OncologyAviano, PN, Italy.
RP Muraro, E (reprint author), Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Translational Research, Immunopathology and Cancer Biomarkers Unit, Aviano, Italy.
EM elemuraro@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2459
EP 2467
DI 10.1007/s12253-020-00859-3
PG 9
ER
PT J
AU Rossat, S
Perrier, H
Lefevre, M
Louvet, Ch
Berre, LN
Chamois, J
Dorel, M
Vacque, D
Guillaudeau, A
Genet, D
Maillet, E
Triby, S
Sabourin, JCh
AF Rossat, Stephane
Perrier, Herve
Lefevre, Marine
Louvet, Christophe
Berre, Le Nathalie
Chamois, Jerome
Dorel, Maryline
Vacque, Daniel
Guillaudeau, Angelique
Genet, Dominique
Maillet, Evelyne
Triby, Simon
Sabourin, Jean-Christophe
TI Drastic Reduction of Turnaround Time After Implementation of a Fully Automated Assay for RAS-BRAF Mutations in Colorectal Cancer: A Pilot Prospective Study in Real-life Conditions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Metastatic colorectal cancer; Mutation analysis; KRAS mutation; BRAF mutation
ID Metastatic colorectal cancer; Mutation analysis; KRAS mutation; BRAF mutation
AB In some situations, there is a need for rapid mutation tests for guiding clinical decisions and starting targeted therapies with minimal delays. In this study we evaluated the turnaround time before and after the implementation of a fully automated multiplex assay for KRAS and NRAS/BRAF mutation tests (Idylla™ platform, Biocartis) in metastatic colorectal cancer. The objective of this project was to compare the turnaround times in 2017–2018 with the fully automated multiplex assay to the 2016 results with previous methods. Centers with a number of tests for metastatic colorectal cancer > 100 yearly and a usual turnaround time ≥ 3 weeks for mutation detection were selected. Results of 505 KRAS tests and 369 NRAS/BRAF tests were transmitted by 10 centers. The mean turnaround time from test prescription to reception of results was reduced from 25.8 days in 2016 to 4.5 days in 2017–2018. In conclusion, this pilot project shows that the Idylla™platform for testing KRAS and NRAS/BRAF mutations allows an optimized turnaround time from test prescription to reception of results.
C1 [Rossat, Stephane] Medipath, Aix-MarseilleEguilles, France.
[Perrier, Herve] Saint-Joseph HospitalMarseille, France.
[Lefevre, Marine] Institute MontsourisParis, France.
[Louvet, Christophe] Institute MontsourisParis, France.
[Berre, Le Nathalie] Ouest PathologieRennes, France.
[Chamois, Jerome] Private Hospital St GregoireSaint-Gregoire, France.
[Dorel, Maryline] Alizes Pathology CenterBaie-Mahault, Guadeloupe, France.
[Vacque, Daniel] Les Eaux Claires ClinicBaie-Mahault, Guadeloupe, France.
[Guillaudeau, Angelique] Limoges PolyclinicLimoges, France.
[Genet, Dominique] Chenieux ClinicLimoges, France.
[Maillet, Evelyne] Pathologie Center MAILLET EvelyneSte Clotilde, La Reunion, France.
[Triby, Simon] AMGEN FranceBoulogne-Billancourt, France.
[Sabourin, Jean-Christophe] Rouen University HospitalRouen, France.
RP Sabourin, JCh (reprint author), Rouen University Hospital, Rouen, France.
EM sabourinjc@gmail.com
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INCa. Plan Cancer 2014–2019 https://www.e-cancer.fr/Expertiseset- publications/Catalogue-des-publications/Plan-Cancer-2014- 2019
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2469
EP 2473
DI 10.1007/s12253-020-00818-y
PG 5
ER
PT J
AU Kuronya, Zs
Szonyi, DM
Nagyivanyi, K
Gyergyay, F
Geczi, L
Budai, B
Martin, T
Ladanyi, A
Kiss, E
Biro, K
AF Kuronya, Zsofia
Szonyi, Daniel Mihaly
Nagyivanyi, Krisztian
Gyergyay, Fruzsina
Geczi, Lajos
Budai, Barna
Martin, Tamas
Ladanyi, Andrea
Kiss, Edina
Biro, Krisztina
TI Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Kidney cancer; Pazopanib; Livermetastasis; Side effects; Efficacy
ID Kidney cancer; Pazopanib; Livermetastasis; Side effects; Efficacy
AB Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8–22.4); and 30.2 months (95% CI: 20.3–41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.
C1 [Kuronya, Zsofia] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Szonyi, Daniel Mihaly] Semmelweis UniversityBudapest, Hungary.
[Nagyivanyi, Krisztian] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Gyergyay, Fruzsina] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Geczi, Lajos] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Budai, Barna] Orszagos Onkologiai Intezet, Molekularis Genetika OsztalyBudapest, Hungary.
[Martin, Tamas] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Ladanyi, Andrea] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Kiss, Edina] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Biro, Krisztina] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
RP Kuronya, Zs (reprint author), National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology Department, 1122 Budapest, Hungary.
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424
National Comprehensive Cancer Network NCCN clinical practice guidelines in oncology, 2019
Mihaly Z, Sztupinszki Z, Surowiak P, Gyorffy B, 2012, A comprehensive overview of targeted therapy in metastatic renal cell carcinoma. Curr Cancer Drug Targets 12:857–872
Sloan B, Scheinfeld NS, 2008, Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr Opin Investig Drugs 9:1324–1335
Sternberg CN, Davis ID,Mardiak J, Szczylik C, Lee E,Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarba JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE, 2010, Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068
Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID, 2013, A randomised, doubleblind phase III study of pazopanib in patients with advanced and/ or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer 49:1287–1296
Administration FaD, 2009, NDA Approval
Nieto M, Borregaard J, Ersboll J, ten Bosch GJA, van Zwieten- Boot B, Abadie E, Schellens JHM, Pignatti F, 2011, The European medicines agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee forMedicinal Products for human use. Clin Cancer Res 17:6608–6614
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK, 2013, Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731
Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK, 2014, Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med 370:1769–1770
Escudier BPC, Bono P, 2014, Randomized, controlled, doubleblind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES study. J Clin Oncol 32:1412–1418
Motzer RJ, Mazumdar M, Bacik J, BergW, Amsterdam A, Ferrara J, 1999, Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540
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Maraz A, Bodrogi I, Csejtei A, Dank M, Geczi L, Kuronya Z, Mangel L, Petranyi A, Szucs M, Bodoky G, 2013, First Hungarian experience with pazopanib therapy for patients with metastatic renal cancer. Magy Onkol 57:173–176
Schmidinger M, Bamias A, Procopio G, Hawkins R, Sanchez AR, Vazquez S, Srihari N, Kalofonos H, Bono P, Pisal CB, Hirschberg Y, Dezzani L, Ahmad Q, Jonasch E, PRINCIPAL Study Group, 2019, Prospective observational study of pazopanib in patients with advanced renal cell carcinoma, PRINCIPAL study). Oncologist 24:491–497
Nazha S, Tanguay S, Kapoor A, Jewett M, Kollmansberger C, Wood L, Bjarnason G, Heng D, Soulieres D, Reaume N, Basappa N, Levesque E, Dragomir A, 2018, Use of targeted therapy in patients with metastatic renal cell carcinoma: clinical and economic impact in a Canadian real-life setting. Curr Oncol 25:e576–e584
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Di Fiore F, Rigal O, Menager C, Michel P, Pfister C, 2011, Severe clinical toxicities are correlated with survival in patients with advanced renal cell carcinoma treated with sunitinib and sorafenib. Br J Cancer 105:1811–1813
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2475
EP 2481
DI 10.1007/s12253-020-00853-9
PG 7
ER
PT J
AU Tas, F
Erturk, K
AF Tas, Faruk
Erturk, Kayhan
TI De Novo and Nevus-Associated Melanomas: Different Histopathologic Characteristics but Similar Survival Rates
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Melanoma; de novo; Nevus-associated; Survival
ID Melanoma; de novo; Nevus-associated; Survival
AB The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51 years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2mm(p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.
C1 [Tas, Faruk] Istanbul Medical Faculty, Istanbul University, Oncology Institute, Capa, 34390 Istanbul, Turkey.
[Erturk, Kayhan] Koc University, Department of Medical OncologyIstanbul, Turkey.
RP Tas, F (reprint author), Istanbul Medical Faculty, Istanbul University, Oncology Institute, 34390 Istanbul, Turkey.
EM faruktas2002@yahoo.com
CR Siegel RL, Miller KD, Jemal A, 2020, Cancer statistics, 2020. CA Cancer J Clin 70:7–30
Cymerman RM, Shao Y, Wang K, Zhang Y, Murzaku EC, Penn LA et al, 2016, De novo vs nevus-associated melanomas: differences in associations with prognostic indicators and survival. J Natl Cancer Inst 108(10):djw121
Haenssle HA, Mograby N, Ngassa A, Buhl T, Emmert S, Schon MP et al, 2016, Association of patient risk factors and frequency of nevus-associated cutaneous melanomas. JAMA Dermatol 152: 291–298
Shitara D, Nascimento MM, Puig S, Yamada S, Enokihara M, Michalany N et al, 2014, Nevus-associated melanomas: clinicopathologic features. Am J Clin Pathol 142:485–491
Pampena R, Kyrgidis A, Lallas A, Moscarella E, Argenziano G, Longo C et al, 2017, A meta-analysis of nevus-associated melanoma: prevalence and practical implications. J AmAcad Dermatol 77: 938–945
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2483
EP 2487
DI 10.1007/s12253-020-00858-4
PG 5
ER
PT J
AU Marta, NG
Velho, IP
Bonadio, R
Nardo, M
Faraj, Sh
Manoel Carlos, dAS
Muniz, D
Bastos, AD
Dzik, C
AF Marta, Nader Guilherme
Velho, Isaacsson Pedro
Bonadio, R. C. Renata
Nardo, Mirella
Faraj, F. Sheila
Manoel Carlos, L. de Azevedo Souza
Muniz, Q. B. David
Bastos, Assed Diogo
Dzik, Carlos
TI Prognostic Value of Systemic Inflammatory Biomarkers in Patients with Metastatic Renal Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Renal cell carcinoma; Pazopanib; Sunitinib; Neutrophil-to-lymphocyte ratio; Platelet-to-lymphocyte ratio
ID Renal cell carcinoma; Pazopanib; Sunitinib; Neutrophil-to-lymphocyte ratio; Platelet-to-lymphocyte ratio
AB Metastatic renal cell carcinoma (mRCC) encompasses a heterogeneous group of neoplasms with distinct clinical behavior and prognoses. As a result of the increasing number of therapeutic options in the metastatic setting, it is crucial to improve prognostic stratification ability. We aimed to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and combination platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with mRCC. We evaluated a cohort of mRCC patients treated with first-line pazopanib or sunitinib. Levels of NLR, PLR and COP-NLR were measured prior to systemic treatment and evaluated as prognostic predictors. Primary endpoint was overall survival (OS). Data from 276 patients were included, of which 54.7%received first-line pazopanib and 45.3%, sunitinib. Memorial Sloan-Kettering Cancer Center risk classification was intermediate and poor in 50% and 42.6% of patients, respectively. High NLR (> 3.5) was associated with inferior OS (median 9.6 vs 17.8 months, P < 0.001). A high PLR (> 200) was associated with inferior OS (median 10.3 vs 17 months, P = 0.002). The median OS in the COP-NLR 1, 2 and 3 groups were 19.0 months (95% CI 15.3–26.0), 13.1 months (95% CI 9.8–17.0) and 7.4 months (95% CI 3.6–11.9), respectively (P < 0.001). In the multivariate analysis, high NLR and high COP-NLR were associated with inferior OS. Both high NLR and high COP-NLR were associated with poorer OS in our cohort of patients with mRCC treated with first-line pazopanib or sunitinib.
C1 [Marta, Nader Guilherme] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Velho, Isaacsson Pedro] Johns Hopkins University, Johns Hopkins Sidney Kimmel Cancer CenterBaltimore, MD, USA.
[Bonadio, R. C. Renata] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Nardo, Mirella] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Faraj, F. Sheila] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Manoel Carlos, L. de Azevedo Souza] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Muniz, Q. B. David] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Bastos, Assed Diogo] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
[Dzik, Carlos] Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251, 01246-000 Sao Paulo, SP, Brazil.
RP Marta, NG (reprint author), Instituto do Cancer do Estado de Sao Paulo, 01246-000 Sao Paulo, Brazil.
EM guilherme.marta@usp.br
CR Siegel RL, Miller KD, Jemal A, 2018, Cancer statistics, 2018. CA Cancer J Clin 68:7–30. , DOI 10.3322/caac.21442
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Motzer RJ, Mazumdar M, Bacik J et al, 1999, Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2530. , DOI 10.1200/JCO. 1999.17.8.2530
Heng DYC, Xie W, Regan MM et al, 2009, Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799. , DOI 10.1200/JCO.2008.21.4809
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2489
EP 2497
DI 10.1007/s12253-020-00840-0
PG 9
ER
PT J
AU Wojtukiewicz, M
Mysliwiec, M
Sierko, E
Sobierska, M
Kruszewska, J
Lipska, A
Radziwon, P
Tucker, S
Honn, K
AF Wojtukiewicz, Z. Marek
Mysliwiec, Marta
Sierko, Ewa
Sobierska, Monika
Kruszewska, Joanna
Lipska, Alina
Radziwon, Piotr
Tucker, C. Stephanie
Honn, V. Kenneth
TI Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Endothelium-derived microparticles; Blood coagulation; Angiogenesis; Colorectal cancer
ID Endothelium-derived microparticles; Blood coagulation; Angiogenesis; Colorectal cancer
AB Hypercoagulable state and neoangiogenesis are common phenomena associated with malignancy. Cancer patients have increased levels of circulating endothelium-derived microparticles (EMPs), which have been hypothesized to be involved in numerous pathophysiological processes. Hemostasis and angiogenesis are also activated in colorectal cancer (CRC) patients. The study aimed to investigate potential influence of chemotherapy on EMPs, thrombin anti-thrombin complex (TAT) and vascular endothelial growth factor (VEGF) levels in CRC patients undergoing chemotherapy. The study group consisted of 18 CRC patients: 8 stage III colon cancer (CC) and 10 stage IV rectal cancer (RC) patients. EMPs, TAT and VEGF levels were assessed before chemotherapy and after the third course. Results were compared with 10 healthy subjects. EMP concentration was measured by flow cytometry, while TAT and VEGF concentrations were assayed employing ELISA. Compared to the control group, CC and RC patients had significantly higher levels of tissue factor (TF)-bearing and non-TF-bearing EMPs before and after three courses of chemotherapy. VEGF concentrations in CRC patients were higher than in the control groups and increased following chemotherapy. TAT levels were elevated in CRC patients before chemotherapy compared to healthy subjects and significantly increased after the third course of chemotherapy. No significant correlation was found either betweenEMP and TAT levels, or between EMP concentrations and VEGF levels in the study group. CRC patients have increased EMPs, and TAT as well as VEGF levels tend to increase during chemotherapy.
C1 [Wojtukiewicz, Z. Marek] Medical University of Bialystok, Department of Oncology, 12 Ogrodowa St, 15-027 Bialystok, Poland.
[Mysliwiec, Marta] Medical University of Bialystok, Department of Oncology, 12 Ogrodowa St, 15-027 Bialystok, Poland.
[Sierko, Ewa] Medical University of Bialystok, Department of Oncology, 12 Ogrodowa St, 15-027 Bialystok, Poland.
[Sobierska, Monika] Medical University of Bialystok, Department of Oncology, 12 Ogrodowa St, 15-027 Bialystok, Poland.
[Kruszewska, Joanna] Medical University of Bialystok, Department of Oncology, 12 Ogrodowa St, 15-027 Bialystok, Poland.
[Lipska, Alina] Regional Centre for Transfusion MedicineBialystok, Poland.
[Radziwon, Piotr] Regional Centre for Transfusion MedicineBialystok, Poland.
[Tucker, C. Stephanie] Wayne State University, Department of Pharmacology, 48202 Detroit, MI, USA.
[Honn, V. Kenneth] Wayne State University, Department of Pharmacology, 48202 Detroit, MI, USA.
RP Wojtukiewicz, M (reprint author), Medical University of Bialystok, Department of Oncology, 15-027 Bialystok, Poland.
EM mzwojtukiewicz@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2499
EP 2507
DI 10.1007/s12253-020-00854-8
PG 9
ER
PT J
AU Marquet, B
Bressenot, MA
Fichel, C
Bouland, N
Barbe, C
Bouche, O
Kianmanesh, R
Diebold, MD
Boulagnon-Rombi, C
AF Marquet, Benjamin
Bressenot, Marchal Aude
Fichel, Caroline
Bouland, Nicole
Barbe, Coralie
Bouche, Olivier
Kianmanesh, Reza
Diebold, Marie-Daniele
Boulagnon-Rombi, Camille
TI Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal neoplasms; AnnexinA10; Gremlin1; Prognosis; Serrated adenocarcinoma
ID Colorectal neoplasms; AnnexinA10; Gremlin1; Prognosis; Serrated adenocarcinoma
AB Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p < 0.001), differentiation grade 3 (p < 0.001), serrated adenocarcinoma subtype (p < 0.001), serrated (p < 0.001), medullary (p = 0.005), and mucinous component (p = 0.004), cytoplasmic eosinophilia (p < 0.001), discernible nuclei (p = 0.001), preserved polarity (p < 0.001), lymphatic invasion (p = 0.01), BRAFV600E mutation (p < 0.001), MSI-H status (p < 0.001) and CIMP-H status (p = 0.019). Multivariate analyses revealed that mucinous component (p = 0.002), lymphatic invasion (p = 0.02) and BRAFV600E mutation (p < 0.001) were independently associated with AnnexinA10 expression. In addition, AnnexinA10 was an indicator of poorer overall survival (OS) in UICC stage IV adenocarcinomas (p = 0.01) only. Gremlin1 expression was neither associated with serrated adenocarcinoma subtype (p = 0.51) nor with AnnexinA10 expression (p = 0,31), but was significantly associated, in univariate analysis with male gender (p = 0.002), younger age (p = 0.002), left tumor location (p=0.04), andMSS status (p = 0.03). Gremlin1 expression was associated with better OS only in UICC stage III colon adenocarcinomas (p = 0.006). Colon adenocarcinomas expressing AnnexinA10 have distinct clinico-pathological and molecular features. AnnexinA10 expression is an indicator of poorer OS in UICC stage IV patients. Gremlin1 expression is not associated with serrated adenocarcinomas subtype. Its expression was associated with better OS in UICC Stage III patients.
C1 [Marquet, Benjamin] Academic Hospital, Department of Biopathology, rue du General Koenig, 51100 Reims, France.
[Bressenot, Marchal Aude] Academic Hospital, Department of Biopathology, rue du General Koenig, 51100 Reims, France.
[Fichel, Caroline] Medicine University, Department of PathologyReims, France.
[Bouland, Nicole] Medicine University, Department of PathologyReims, France.
[Barbe, Coralie] Academic Hospital, Clinical Research UnitReims, France.
[Bouche, Olivier] Academic Hospital, Gatroenterology and Digestive Oncology DepartmentReims, France.
[Kianmanesh, Reza] Academic Hospital, Digestive Surgery DepartmentReims, France.
[Diebold, Marie-Daniele] Academic Hospital, Department of Biopathology, rue du General Koenig, 51100 Reims, France.
[Boulagnon-Rombi, Camille] Academic Hospital, Department of Biopathology, rue du General Koenig, 51100 Reims, France.
RP Marquet, B (reprint author), Academic Hospital, Department of Biopathology, 51100 Reims, France.
EM marquetbenjamin@orange.fr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2509
EP 2521
DI 10.1007/s12253-020-00857-5
PG 13
ER
PT J
AU Hegedus, L
Rittler, D
Garay, T
Stockhammer, P
Kovacs, I
Dome, B
Theurer, S
Hager, Th
Herold, Th
Kalbourtzis, S
Bankfalvi,
Schmid, K
Fuhrer, D
Aigner, C
Hegedus, B
AF Hegedus, Luca
Rittler, Dominika
Garay, Tamas
Stockhammer, Paul
Kovacs, Ildiko
Dome, Balazs
Theurer, Sarah
Hager, Thomas
Herold, Thomas
Kalbourtzis, Stavros
Bankfalvi, Agnes
Schmid, W. Kurt
Fuhrer, Dagmar
Aigner, Clemens
Hegedus, Balazs
TI HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Anaplastic thyroid cancer; BRAF mutation; TERT promoter mutation; HDAC inhibition; Pleural effusion
ID Anaplastic thyroid cancer; BRAF mutation; TERT promoter mutation; HDAC inhibition; Pleural effusion
AB While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations are needed for specific subsets of patients. We established a novel cell line (PF49) from the malignant pleural effusion of a 68-year-old male patient with ATC that rapidly transformed from a BRAF and TERT promoter mutant PTC. PF49 cells demonstrated a robust migratory activity in vitro and strong invasive capacity in vivo in a pleural carcinosis model. Combined BRAF andMEK inhibition decreased the proliferation and migration of PF49 cells, however could not induce cell death. Importantly, HDAC inhibitor treatment with SAHA or valproic acid induced cell cycle arrest and strongly increased PD-L1 expression of the tumor cells. Induction of PD-L1 expression was also present when paclitaxelcisplatin chemotherapeutic treatment was combined with HDAC inhibitor treatment. Increased PD-L1 expression after HDAC inhibition was recapitulated in an international ATC cell model. Our data suggest that HDAC inhibition alone or in combination with standard chemotherapy may potentiate anaplastic thyroid cancer cells for immunotherapy.
C1 [Hegedus, Luca] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Rittler, Dominika] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Garay, Tamas] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Stockhammer, Paul] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Kovacs, Ildiko] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Dome, Balazs] Medical University of Vienna, Department of Thoracic SurgeryVienna, Austria.
[Theurer, Sarah] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Hager, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Herold, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Kalbourtzis, Stavros] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Bankfalvi, Agnes] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Schmid, W. Kurt] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Fuhrer, Dagmar] University Duisburg-Essen, University Clinic Essen, Department of EndocrinologyEssen, Germany.
[Aigner, Clemens] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Balazs] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
RP Hegedus, B (reprint author), University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic Surgery, Essen, Germany.
EM balazs.hegedues@rlk.uk-essen.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2523
EP 2535
DI 10.1007/s12253-020-00834-y
PG 13
ER
PT J
AU Tabuso, M
Christian, M
Kimani, P
Gopalakrishnan, K
Arasaradnam, R
AF Tabuso, Maria
Christian, Mark
Kimani, K. Peter
Gopalakrishnan, Kishore
Arasaradnam, Ramesh
TI KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; KRAS; Metabolic syndrome; Tumour location; Lipids
ID Colorectal cancer; KRAS; Metabolic syndrome; Tumour location; Lipids
AB Colorectal cancer (CRC) is characterized by complex interplay between macroenvironmental factors and tumour microenvironment, leading to variable outcomes in CRC patients. To date, there is still a need to identify macroenvironment/microenvironment factors that could define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy. Aim of this study was to evaluate associations between metabolic parameters and KRAS status in metastatic CRC (mCRC) according to a new tumour site classification. Retrospective data were extracted from a total of 201 patients diagnosed with mCRC between 2012 and 2017 extracted from an established CRC database at our tertiary institute. Clinical-pathological data, including age, gender, BMI, hypertension, diabetes, pre-CRC diagnosis serum lipid levels and KRAS status were recorded. Categorical characteristics were compared using chi-squared test. Continuous characteristics were compared using Mann-Whitney U test. Log rank test was used to compare hazards for survival. In all comparisons, a two-sided P value <0.05 was considered statistically significant. Out of 201 patients, 170 patients with complete serum lipid profile were included in the analysis. In recto-sigmoid cancers there was a statistically significant association between high cholesterol:high-density lipoprotein (chol:HDL) ratio and KRAS mutation (OR 2.69, 95% CI 1.1–6.4, p = 0,02). In non recto-sigmoid cancers, high cholesterol was associated with KRAS WT (OR 0.39, CI 0.15–0.97, p = 0.04). In 22 patients with KRAS mutated recto-sigmoid cancer stage IV at diagnosis normal chol:HDL ratio was associated with a trend to better survival (p = 0.06).High chol:HDL ratiowas significantly associated with KRAS mutatedmetastatic recto-sigmoid cancers. A subgroup of mCRC patients with KRAS mutated recto-sigmoid cancer may benefit from optimal lipid lowering treatment.
C1 [Tabuso, Maria] University Hospital Coventry and Warwickshire, Department of Gastroenterology, Clifford Bridge Road, CV2 2DX Coventry, UK.
[Christian, Mark] Nottingham Trent University, School of Science and Technology, NG11 8NS Nottingham, UK.
[Kimani, K. Peter] University of Warwick, Warwick Medical School, CV4 7AL Coventry, UK.
[Gopalakrishnan, Kishore] University Hospitals of Coventry and Warwickshire NHS Trust, Department of Pathology, Clifford Bridge Road, CV2 2DX Coventry, UK.
[Arasaradnam, Ramesh] University Hospital Coventry and Warwickshire, Department of Gastroenterology, Clifford Bridge Road, CV2 2DX Coventry, UK.
RP Tabuso, M (reprint author), University Hospital Coventry and Warwickshire, Department of Gastroenterology, CV2 2DX Coventry, UK.
EM Maria.Tabuso@uhcw.nhs.uk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2537
EP 2548
DI 10.1007/s12253-020-00850-y
PG 12
ER
PT J
AU Molnar, Sz
Beke, L
Mehes, G
Poka, R
AF Molnar, Szabolcs
Beke, Livia
Mehes, Gabor
Poka, Robert
TI The Prognostic Value of PARP Expression in High-Grade Epithelial Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Ovarian cancer; PARP expression; Gynaecological oncology; Platinum-based chemotherapy; Progression-free survival
ID Ovarian cancer; PARP expression; Gynaecological oncology; Platinum-based chemotherapy; Progression-free survival
AB In an attempt to clarify the prognostic relevance of poly (ADP-ribose) polymerase (PARP) expression, we analysed the clinical data of 86 high-grade epithelial ovarian cancer (EOC) cases in which PARP immunohistochemistry results were available. Immunostaining to highlight PARP protein expression was performed using a Leica Bond MAX Immunostainer (Leica Microsystems, Wetzlar, Germany). We applied a rabbit polyclonal anti-PARP antibody (ab6079 330, Abcam, Cambridge, UK) for the specific reaction. The intensity and distribution of immunostaining were assessed by light microscopy (Leica DM2500 microscope, DFC 420 camera, and Leica Application Suite V3 software; Leica) and evaluated with a four-grade (0– 3+) system. The median progression-free survival (PFS) was generated for each semiquantitative group of PARP expression among chemotherapy-naive cases at the time of PARP immunohistochemistry. Eighty-six cases were chemotherapy-naive at the time of PARP immunohistochemistry, and 41 cases showed no PARP expression. Forty-five cases showed intermediate or high PARP expression. The median PFS among patients in the PARP-negative group was 16 months (interquartile range; IQR 10.7– 35.9 months), and the median PFS of patients in the PARP-positive group was 12 months (IQR 6.1–21.8 months). The difference was significant according to the log-rank test (p = 0.01). The median overall survival (OS) of patients in the PARP-negative group was 65 months (IQR 43.6–110.8 months), and the median OS of patients in the PARP-positive group was 52 months (IQR 36.9– 66.7 months). The difference was significant according to the log-rank test (p = 0.028). Multiple comparisons confirmed that PARP expression results in a significant difference in PFS and OS achieved by first-line Taxol-carboplatin chemotherapy. The lack of PARP expression assessed by immunohistochemistry may predict improved PFS in ovarian cancer patients after adjuvant platinum-based chemotherapy.
C1 [Molnar, Szabolcs] University Medical School of Debrecen, Department of Gynecology and Obstetrics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Beke, Livia] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of Pathology, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
[Poka, Robert] University Medical School of Debrecen, Department of Gynecology and Obstetrics, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
RP Molnar, Sz (reprint author), University Medical School of Debrecen, Department of Gynecology and Obstetrics, 4032 Debrecen, Hungary.
EM szmolnar.md@gmail.com
CR Ataseven B, GrimmC,Harter P, Prader S, Traut A, Heitz F, du Bois A, 2014, Prognostic value of lymph node ratio in patients with advanced epithelial ovarian cancer. Gynecol Oncol 135:435–440
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2549
EP 2555
DI 10.1007/s12253-020-00856-6
PG 7
ER
PT J
AU Koroknai, V
Patel, V
Szasz, I
Adany, R
Balazs, M
AF Koroknai, Viktoria
Patel, Vikas
Szasz, Istvan
Adany, Roza
Balazs, Margit
TI Gene Expression Signature of BRAF Inhibitor Resistant Melanoma Spheroids
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 2D and 3D cell culture; Spheroids; Gene expression and BRAF inhibitor resistance; Melanoma cell lines
ID 2D and 3D cell culture; Spheroids; Gene expression and BRAF inhibitor resistance; Melanoma cell lines
AB In vitro cell cultures are frequently used to define the molecular background of drug resistance. The majority of currently available data have been obtained from 2D in vitro cultures, however, 3D cell culture systems (spheroids) are more likely to behave similarly to in vivo conditions. Our major aim was to compare the gene expression signature of 2D and 3D cultured BRAFV600E mutant melanoma cell lines. We successfully developed BRAF-drug resistant cell lines from paired primary/ metastatic melanoma cell lines in both 2D and 3D in vitro cultures. Using Affymetrix Human Gene 1.0 ST arrays, we determined the gene expression pattern of all cell lines. Our analysis revealed 1049 genes (562 upregulated and 487 downregulated) that were differentially expressed between drug-sensitive cells grown under different cell cultures. Pathway analysis showed that the differently expressed genes were mainly associated with the cell cycle, p53, and other cancer-related pathways. The number of upregulated genes (72 genes) was remarkably fewer when comparing the resistant adherent cells to cells that grow in 3D, and were associated with cell adhesion molecules and IGF1R signalling. Only 1% of the upregulated and 5.6% of the downregulated genes were commonly altered between the sensitive and the resistant spheroids. Interestingly, we found several genes (BNIP3, RING1 and ABHD4) with inverse expression signature between sensitive and resistant spheroids, which are involved in anoikis resistance and cell cycle regulation. In summary, our study highlights gene expression alterations that might help to understand the development of acquired resistance in melanoma cells in tumour tissue.
C1 [Koroknai, Viktoria] Debreceni Egyetem, Nepegeszsegugyi Iskola, Kassai St 26/B, H-4028 Debrecen, Hungary.
[Patel, Vikas] Debreceni Egyetem, Nepegeszsegugyi Iskola, Kassai St 26/B, H-4028 Debrecen, Hungary.
[Szasz, Istvan] Debreceni Egyetem, Nepegeszsegugyi Iskola, Kassai St 26/B, H-4028 Debrecen, Hungary.
[Adany, Roza] Debreceni Egyetem, Nepegeszsegugyi Iskola, Kassai St 26/B, H-4028 Debrecen, Hungary.
[Balazs, Margit] Debreceni Egyetem, Nepegeszsegugyi Iskola, Kassai St 26/B, H-4028 Debrecen, Hungary.
RP Balazs, M (reprint author), Debreceni Egyetem, Nepegeszsegugyi Iskola, H-4028 Debrecen, Hungary.
EM balazs.margit@sph.unideb.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2557
EP 2566
DI 10.1007/s12253-020-00837-9
PG 10
ER
PT J
AU Aralica, G
Sarec Ivelj, M
Pacic, A
Bakovic, J
Milkovic Perisa, M
Kristic, A
Konjevoda, P
AF Aralica, Gorana
Sarec Ivelj, Martina
Pacic, Arijana
Bakovic, Josip
Milkovic Perisa, Marija
Kristic, Anteja
Konjevoda, Pasko
TI Prognostic Significance of Lacunarity in Preoperative Biopsy of Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; Preoperative biopsy; Intratumoral budding; Lacunarity; Prognosis; Recursive partitioning; Image analysis
ID Colorectal cancer; Preoperative biopsy; Intratumoral budding; Lacunarity; Prognosis; Recursive partitioning; Image analysis
AB The quantity and quality of preoperative material in colorectal cancer is often limiting factor in determination of risk factors and therapy planning. The most important negative prognostic factors are intravascular and perineural invasion, as well as tumor budding. Usually, the only parameter available in preoperative biopsy is tumor budding. However, the growing body of evidence suggests that cancer differentiation based on the poorly differentiated clusters has better prognostic value. The limiting factor in applying of these new parameters is reproducible, simple, cheap and fast method of their determination. In this paper we investigated the prognostic value of lacunarity, determined in preoperative biopsy. Lacunarity is a measure of spatial heterogeneity (inhomogeneity) in an image. It quantifies how objects fill the space, and enables analysis of gaps distribution, homogeneity of gaps, and presence of structures. It was shown that lacunarity and the total number of buds could be combined in a model which clearly divides colorectal cancer patients in low, medium and high risk subgroups. The paper also points out that the quantitative numerical methods are superior to semiquantitative methods, and that individual methods should be combined using algorithms to obtain a more accurate prediction. Because the study described is designed as a pilot study, verification is needed on a larger sample of patients from independent researchers.
C1 [Aralica, Gorana] University of Zagreb, School of MedicineZagreb, Croatia.
[Sarec Ivelj, Martina] University of Zagreb, School of MedicineZagreb, Croatia.
[Pacic, Arijana] University Hospital DubravaZagreb, Croatia.
[Bakovic, Josip] University Hospital DubravaZagreb, Croatia.
[Milkovic Perisa, Marija] University of Zagreb, School of MedicineZagreb, Croatia.
[Kristic, Anteja] University of Zagreb, School of MedicineZagreb, Croatia.
[Konjevoda, Pasko] Rudjer Boskovic InstituteZagreb, Croatia.
RP Aralica, G (reprint author), University of Zagreb, School of Medicine, Zagreb, Croatia.
EM garalica@kbd.hr
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2567
EP 2576
DI 10.1007/s12253-020-00851-x
PG 10
ER
PT J
AU Niu, D
Li, L
Yu, Y
Zang, W
Li, Z
Zhou, L
Jia, L
Rao, G
Gao, L
Cheng, G
Ji, K
Lin, D
AF Niu, Dongfeng
Li, Lei
Yu, Yang
Zang, Wanchun
Li, Zhongwu
Zhou, Lixin
Jia, Ling
Rao, Guanhua
Gao, Lianju
Cheng, Gang
Ji, Ke
Lin, Dongmei
TI Evaluation of Next Generation Sequencing for Detecting HER2 Copy Number in Breast and Gastric Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Next generation sequencing; HER2 amplification; Breast cancer; Gastric cancer; FISH/IHC
ID Next generation sequencing; HER2 amplification; Breast cancer; Gastric cancer; FISH/IHC
AB Amplicon-based next generation sequencing (NGS) approaches have been preferentially adopted by the clinical laboratories on the basis of a short turnaround time (TAT) and small DNA input needs. However, little work has been done to assess the amplicon-based NGS methods for copy number variation (CNV) detection in comparison with current standard methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The correlation between NGS based CNV detection and the later standard methods has remained unexplored. We developed an amplicon-based panel to detect human epidermal receptor growth factor (HER2) amplification in formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 280 breast cancer and 50 gastric cancer patients. Assessment by IHC and FISH was conducted in parallel, and descriptive statistics were used to assess the concordance. The copy number detected by NGS was correlated with either the average HER2 copy number (signals/cell) (r = 0.844; p < 0.001) or the HER2/CEP17 ratio (r = 0.815; p < 0.001). We determined a cut-off value for NGS to categorize HER2 amplification status by using 151 HER2 non-amplified FFPE samples. In breast cancer patients, the cut-off value was 2.910, with 95.35%, 98.67% and 97.29% sensitivity, specificity and concordance, respectively. However, this cut-off value displayed low sensitivity in gastric cancer patients (64.71%), and the following macrodissection procedure was not effective for increasing sensitivity (57.14%). Evaluation of HER2 copy number with NGS in our study was comparable with IHC and FISH in breast cancer patients, but concordance in gastric cancer was only moderate. The greater discordance in gastric cancer may reflect the underlying biological mechanisms, and further study is warranted. NGS-based HER2 assessment may decrease the equivocal HER2 determinations in breast cancer patients assessed by FISH/IHC.
C1 [Niu, Dongfeng] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyBeijing, China.
[Li, Lei] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Yu, Yang] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Zang, Wanchun] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Li, Zhongwu] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyBeijing, China.
[Zhou, Lixin] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyBeijing, China.
[Jia, Ling] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyBeijing, China.
[Rao, Guanhua] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Gao, Lianju] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Cheng, Gang] Beijing Novogene Bioinformatics Technology Co., LtdBeijing, China.
[Ji, Ke] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal SurgeryBeijing, China.
[Lin, Dongmei] Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyBeijing, China.
RP Lin, D (reprint author), Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Beijing, China.
EM Dongm_lin@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2577
EP 2585
DI 10.1007/s12253-020-00844-w
PG 9
ER
PT J
AU Choi, S
Park, S
Cho, AY
Park, ChK
Ha, YS
AF Choi, Sangjoon
Park, Sujin
Cho, Ah Yoon
Park, Cheol-Keun
Ha, Yun Sang
TI Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hepatocellular carcinoma; Prognosis; NTRK; Trk; Target
ID Hepatocellular carcinoma; Prognosis; NTRK; Trk; Target
AB Oncogenic fusion of the tropomyosin receptor kinase (Trk) receptor family encoded by the NTRK gene has been found in several carcinomas. About ten targeted therapies have been developed and clinical trials are in progress. However, the results of studies on expression of the Trk receptor in HCC have not yet been published. Immunohistochemical staining was performed using anti- TrkA+B+C antibody (ab181560, Abcam) in 288 curatively resected primary HCC samples, and the correlation between Trk expression and NTRK copy number was assessed. Targeted next generation sequencing was performed in cases with Trk overexpression to detect NTRK fusion genes. Overexpression of Trk protein was observed in 21 (7.3%) of 288 cases. The Trk overexpression group showed a trend toward shorter recurrence-free survival (RFS) (p = 0.092) and overall survival (OS) (p = 0.079) than the low expression group, with frequent multicentric occurrence. Differences in RFS and OS were statistically significant in specific sub-populations including AJCC T1 stage HCCs, tumors less than 5 cm, patients without cirrhosis, tumors without vascular invasion, or Edmondson grades I and II. Trk expression was also an independent prognostic factor in both RFS and OS. Trk expression was not associated with copy number of each NTRK gene, and NTRK fusion was not detected in HCCs with Trk overexpression. Trk expression might play an important role in the development and progression of HCC, and emerging target therapy against the Trk protein could be applicable in patients with Trk-overexpressing HCC.
C1 [Choi, Sangjoon] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, South Korea.
[Park, Sujin] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, South Korea.
[Cho, Ah Yoon] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, South Korea.
[Park, Cheol-Keun] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, South Korea.
[Ha, Yun Sang] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, South Korea.
RP Ha, YS (reprint author), Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Pathology, 06351 Seoul, South Korea.
EM sangyun.ha@skku.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2587
EP 2595
DI 10.1007/s12253-020-00871-7
PG 9
ER
PT J
TI Novel CXCR4 Inhibitor CPZ1344 Inhibits the Proliferation, Migration and Angiogenesis of Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CXCR4; CPZ1344; Migration; Glioblastoma
ID CXCR4; CPZ1344; Migration; Glioblastoma
AB Glioblastoma (GBM) are life-threatening tumors with a poor prognosis and low cure rates. GBMs are malignant brain tumors that develop from astrocytes. Most GBMs are not inherited and occur sporadically. GBM recurrence after standard treatment has led to the assessment of agents targeting the CXCR4 chemokine receptor as alternative drug target for much needed GBM therapeutics. In present study, a novel CXCR4 inhibitor modified with a picolinamide scaffold (CPZ1344) was designed and synthesized. Its anti-GBM function was then evaluated. Our results showed that CPZ1344 reduced the growth of GBM cells in a concentration dependent manner. The anti-GBM activity of CPZ1344 was due to alteration in GBM-cell morphology and apoptotic induction in GBM cells. CPZ1344 inhibited the migration and angiogenesis of U87 cells, led to cell cycle arrest in the G1 phase and inhibited CXCR4 signaling. These findings demonstrate the anticancer effects of CPZ1344 and its potential as a novel anti-GBM therapeutic.
CR Omuro A,DeAngelisLM(2013)Glioblastoma and othermalignant gliomas: a clinical review. Jama 310, 17): 1842–1850
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Fianco G, Contadini C, Ferri A, Cirotti C, Stagni V, Barila D, 2018, Caspase-8: A Novel Target to Overcome Resistance to Chemotherapy in Glioblastoma. Int J Mol Sci 19, 12): 3798
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2597
EP 2604
DI 10.1007/s12253-020-00827-x
PG 8
ER
PT J
AU Soenens, Ch
Dekuyper, P
De Coster, G
Van Damme, N
Van Eycken, E
Quackels, Th
Roumeguere, Th
Van Cleynenbreugel, B
Joniau, S
Ameye, F
AF Soenens, Charlotte
Dekuyper, Peter
De Coster, Greet
Van Damme, Nancy
Van Eycken, Elizabeth
Quackels, Thierry
Roumeguere, Thierry
Van Cleynenbreugel, Ben
Joniau, Steven
Ameye, Filip
TI Concordance Between Biopsy and Radical Prostatectomy Gleason Scores: Evaluation of Determinants in a Large-Scale Study of Patients Undergoing RARP in Belgium
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Prostate cancer; Gleason score; Concordance; Upgrading; Center size
ID Prostate cancer; Gleason score; Concordance; Upgrading; Center size
AB To determine whether Gleason scores were concordant between prostate biopsies (bGS) and the definitive resection specimen (pGS) excised with robot-assisted radical prostatectomy (RARP); to identify clinical and pathological factors that might predict upgrading; and to evaluate how upgrading affected outcome. Between 2009 and 2016, 25 Belgian centers participated in collecting prospective data for patients that underwent RARP. We analyzed the concordance rate between the bGS and the pGS in 8021 patients with kappa statistics, and we compared concordance rates from different centers. We assessed the effect of several clinical and pathological factors on the concordance rate with logistic regression analysis. The concordance rate for the entire population was 62.9%. Upgrading from bGS to pGS occurred in 27.3% of patients. The number of biopsies was significantly associated with concordance. Older age (>60 y), a higher clinical T stage (≥cT2), a higher PSA value at the time of biopsy (>10 ng/ml), and more time between the biopsy and the radical prostatectomy were significantly associated with a higher risk of upgrading. Positive margins and PSA relapse occurred more frequently in upgraded patients. Center size did not significantly affect the concordance rate (p = 0.40).This prospective, nationwide analysis demonstrated a Gleason score concordance rate of 62.9%. Upgrading was most frequently observed in the non-concordant group. We identified clinical and pathological factors associated with (non)-concordance. Upgrading was associated with a worse oncological outcome. Center volume was not associated with pathological accuracy.
C1 [Soenens, Charlotte] AZ Maria Middelares, Department of UrologyGhent, Belgium.
[Dekuyper, Peter] AZ Maria Middelares, Department of UrologyGhent, Belgium.
[De Coster, Greet] Belgian Cancer RegistryBrussels, Belgium.
[Van Damme, Nancy] Belgian Cancer RegistryBrussels, Belgium.
[Van Eycken, Elizabeth] Belgian Cancer RegistryBrussels, Belgium.
[Quackels, Thierry] Erasmus Hospital, Department of UrologyBrussels, Belgium.
[Roumeguere, Thierry] Erasmus Hospital, Department of UrologyBrussels, Belgium.
[Van Cleynenbreugel, Ben] University Hospital of Leuven, Department of UrologyLeuven, Belgium.
[Joniau, Steven] University Hospital of Leuven, Department of UrologyLeuven, Belgium.
[Ameye, Filip] AZ Maria Middelares, Department of UrologyGhent, Belgium.
RP Soenens, Ch (reprint author), AZ Maria Middelares, Department of Urology, Ghent, Belgium.
EM charlotte.soenens@azmmsj.be
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2605
EP 2612
DI 10.1007/s12253-020-00860-w
PG 8
ER
PT J
AU Cserni, D
Zombori, T
Voros, A
Stajer, A
Rimovszki, A
Daru, K
Barath, Z
Cserni, G
AF Cserni, Dorottya
Zombori, Tamas
Voros, Andras
Stajer, Anette
Rimovszki, Annamaria
Daru, Krisztian
Barath, Zoltan
Cserni, Gabor
TI A Clinicopathological Approach to Odontogenic Cysts: the Role of Cytokeratin 17 and bcl2 Immunohistochemistry in Identifying Odontogenic Keratocysts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Odontogenic keratocyst; Cytokeratin 17; B cell lymphoma – 2 (bcl2); Dentigerous cyst; Radicular cyst
ID Odontogenic keratocyst; Cytokeratin 17; B cell lymphoma – 2 (bcl2); Dentigerous cyst; Radicular cyst
AB Odontogenic keratocysts (OKCs) are developmental cysts of the jaws that require proper diagnosis due to their potential for local aggressive growth and recurrences. OKCs have a typical parakeratotic epithelium demonstrating transepithelial cytokeratin 17 (CK17) and basal bcl2 staining on immunohistochemistry (IHC), which distinguishes them from other common jaw cysts. Secondary to inflammation, the epithelial lining may be altered and loses the typical IHC phenotype. The aim of the present study was to analyse a series of consecutive jaw cysts for their expression of CK17 and bcl2 and assess how these IHC stains may help in their diagnosis. All cysts were retrospectively assessed for available clinical, radiological and pathological findings and diagnoses were revised whenever needed. 85 cysts from 72 patients were collected from two departments. The series had 21 OKCs, the remaining non-OKCs included radicular/residual, dentigerous, paradental, lateral periodontal, botryoid odontogenic cysts. OKCs with typical epithelium showed the typical IHC phenotype, which was generally lost in inflammation-associated altered epithelium. Contrarily to earlier descriptions, a wide variety of CK17 positivity was seen in the majority of non-OKCs, including focal transepithelial staining. Basal bcl2 staining was also seen in 16 non-OKCs. These stainings were never as strong in intensity as seen in OKCs. One case was histopathologically identified as OKC due to focally maintained IHC profile. CK17 and bcl2 IHCmay help in the diagnosis of OKCs, but must be interpreted with caution and is not a yes or no tool in the diagnostic puzzle.
C1 [Cserni, Dorottya] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
[Zombori, Tamas] University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
[Voros, Andras] University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
[Stajer, Anette] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
[Rimovszki, Annamaria] Bacs-Kiskun County Hospital, Department of Pathology, H-6000 Kecskemet, Hungary.
[Daru, Krisztian] University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
[Barath, Zoltan] University of Szeged, Faculty of Dentistry, Department of Prosthodontics, Tisza Lajos krt 64-66, H-6720 Szeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
RP Cserni, G (reprint author), University of Szeged, Department of Pathology, H-6725 Szeged, Hungary.
EM cserni@freemail.hu
CR El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, 2017, WHO classification of head and neck Tumours, 4th edn. International Agency for Research on Cancer, Lyon
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Barnes L, Eveson JW, Reichart P, Sidransky D, 2005, WHO classification of tumors: pathology and genetics of head and neck tumours, 3rd edn. International Agency for Research on Cancer, Lyon
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Speight PM, Takata T, 2017, New tumour entities in the 4th edition of the World Health Organisation classification of head and neck tumours: odontogenic and maxillofacial bone tumours. Virchows Arch 472:331–339. , DOI 10.1007/s00428-017-2182-3
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2613
EP 2620
DI 10.1007/s12253-020-00866-4
PG 8
ER
PT J
TI The Ratio of ssDNA to dsDNA in Circulating Cell-Free DNA Extract is a Stable Indicator for Diagnosis of Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cfDNA; ssDNA to dsDNA ratio; Gastric cancer; Tumor biomarker; Non-invasive
ID cfDNA; ssDNA to dsDNA ratio; Gastric cancer; Tumor biomarker; Non-invasive
AB Due to the different mechanisms of cell-free DNA production, the single-stranded DNA to double-stranded DNA ratio in blood maybe different between healthy individuals and gastric cancer (GC) patients.We aimed to explore the potential application of this ratio in GC diagnosis. The plasma cell-free DNA extracts from 118 healthy individuals and 106 GC patients were prepared. The levels of singlestranded DNA or double-stranded DNA in plasma, and the single-stranded DNA to double-stranded DNA ratio on the diagnostic efficiency for GC were assessed with ROC curve. The relationships between this ratio and the clinical characteristics of GC patients were analyzed. The ratios in 63 GC patients before and after surgery were compared. In healthy individuals, the single-stranded DNA to double-stranded DNA ratio was not affected by factors including age, gender and BMI, and subjected to normal distribution (P = 0.1090). GC patients had a lower value of this ratio than healthy individuals (P < 0.0001). Considering this ratio as a GC diagnostic indicator, the area under ROC curve (AUC) was 0.923[95% confidence interval (CI):0.880–0.955]. This ratio in unresectable GC was obviously lower than that in resectable GC (P = 0.0045). There was a rank correlation between this ratio and GC TNM staging (rho = −0.266, P = 0.0058), but it had no correlation with tumor size (r = 0.14, P = 0.145). Additionally, this ratio was not affected by hemolysis and repeated freeze-thaw of blood samples, and was significantly elevated after surgery(P < 0.0001). The single-stranded DNA to double-stranded DNA ratio in plasma is a stable non-invasive indicator for GC diagnosis.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2621
EP 2632
DI 10.1007/s12253-020-00869-1
PG 12
ER
PT J
AU Szekerczes, T
Galamb,
Varga, N
Benczik, M
Kocsis, A
Schlachter, K
Kiss, A
Acs, N
Schaff, Zs
Jeney, Cs
Lendvai, G
Sobel, G
AF Szekerczes, Timea
Galamb, Adam
Varga, Norbert
Benczik, Marta
Kocsis, Adrienn
Schlachter, Krisztina
Kiss, Andras
Acs, Nandor
Schaff, Zsuzsa
Jeney, Csaba
Lendvai, Gabor
Sobel, Gabor
TI Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Cervical cancer; Cervical intraepithelial neoplasia (CIN); microRNA; Human papilloma virus
ID Cervical cancer; Cervical intraepithelial neoplasia (CIN); microRNA; Human papilloma virus
AB Cervical cancer is a common malignant tumor worldwide ranking fourth in incidence and mortality among females, which was reduced significantly by cytology screening and human papilloma virus (HPV) DNA testing. The specificity of cytology is high; however, the sensitivity is low, in contrast to the HPV DNA testing. Despite the success of these measures, new biomarkers are still considered to aim increasing sensitivity and specificity of screening and diagnosis. Significant alterations in microRNA (miRNA) expression have been detected in several cancers with variable consistency. To investigate the stratification role of miRNAs between normal epithelium and cervical intraepithelial neoplasia (CIN2–3), we screened the expression of 667 miRNAs to identify significant markers (n = 10), out of them 9 miRNAs were applied in the study (miR-20b, −24, −26a, −29b, −99a, −100, −147, −212, −515-3p) along with RNU48 and U6 as the references. To benchmark the miRNAs, 22 paired (tumor-free and tumor tissue pairs) laser microdissection-obtained cervical formalin fixed, paraffin embedded tissue samples were assayed. The expression of miR-20b was 2.4 times higher in CIN2–3 samples as compared to normal tissues (p < 0.0001). In the HPV16-positive subsets of the samples (n = 13), miR-20b showed 2.9-times elevation (p < 0.001), whereas miR-515 was 1.15-times downregulated (p < 0.05) in CIN2–3 as compared to normal tissue. These results suggest the potential value of miR- 20b as a statification biomarker in order to differentiate neoplastic and non-tumorous cases.
C1 [Szekerczes, Timea] Semmelweis University, 2nd Department of PathologyBudapest, Hungary, Hungary.
[Galamb, Adam] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Ulloi 78/A, 1082 Budapest, Hungary, Hungary.
[Varga, Norbert] Oxford University, Nuffield Department of Clinical Neurosciences, Sleep & Circadian Neuroscience InstituteOxford, UK, UK.
[Benczik, Marta] Synlab Hungary Ltd.Budapest, Hungary, Hungary.
[Kocsis, Adrienn] NEUMANN Diagnostics Ltd.Budapest, Hungary, Hungary.
[Schlachter, Krisztina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary, Hungary.
[Acs, Nandor] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Ulloi 78/A, 1082 Budapest, Hungary, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary, Hungary.
[Jeney, Csaba] Albert-Ludwigs University, Department of Microsystems EngineeringFreiburg, Germany, Germany.
[Lendvai, Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary, Hungary.
[Sobel, Gabor] Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, Ulloi 78/A, 1082 Budapest, Hungary, Hungary.
RP Sobel, G (reprint author), Semmelweis Medical University, Ist Department of Gynaecology and Obstetrics, 1082 Budapest, Hungary.
EM sobelg@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2633
EP 2640
DI 10.1007/s12253-020-00852-w
PG 8
ER
PT J
AU del Arco, DC
Munoz, EL
Manchado, BR
Garcia, PA
Medina, OL
Roldan, ME
Fernandez, SG
Soledad, GGdlH
Acenero, MJF
AF del Arco, Diaz Cristina
Munoz, Estrada Lourdes
Manchado, Barderas Rodrigo
Garcia, Pelaez Alberto
Medina, Ortega Luis
Roldan, Molina Elena
Fernandez, Solis Guillermo
Soledad, Garcia Gomez de las Heras
Acenero, Maria Jesus Fernandez
TI Prognostic Role of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Immunohistochemical Expression in Patients with Resected Gastric Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Gastric cancer; Prognosis; Aryl hydrocarbon receptor interacting protein; AIP; Immunohistochemistry
ID Gastric cancer; Prognosis; Aryl hydrocarbon receptor interacting protein; AIP; Immunohistochemistry
AB Aryl hydrocarbon receptor (AHR) interacting protein (AIP) is a chaperone which binds to inactive AHR in the cell cytoplasm. AHR is best known for mediating the toxicity of halogenated aromatics, but it has also been linked to carcinogenesis and tumor progression in several tumor types. Our aims are to assess the features of AIP immunohistochemical (IHC) staining and to evaluate its possible role as a prognostic marker in gastric cancer (GC). Retrospective study of 147 cases of resected GC. Clinicopathological features were collected, tissue microarrays were constructed for AIP IHC and statistical analysis were performed. AIP staining was observed in 50.3% of tumors. All AIP-positive cases exhibited cytoplasmic or membranous staining, variably associated with nuclear co-staining. 93.2% of AIP-positive tumors showed AIP immunoreactivity in 100% of cells. Staining intensity was mild, moderate and intense in 33.8%, 13.5%and 52.7%of cases. Tumors were stratified according to AIP staining intensity into low expression (no or mild AIP immunoreactivity) and high expression (moderate or intense AIP immunoreactivity). 36.6% of our cases showed high AIP expression. High AIP expression was significantly and independently correlated to tumor progression and cancer death. Tumors with high AIP expression showed lower survival and higher progression rates. AIP expression might be useful for determining GC prognosis. More studies are needed to clarify the role of AHR pathway in GC, AIP expression and its potential use as a surrogate marker for selecting patients for AHR modulation therapy.
C1 [del Arco, Diaz Cristina] Autonomous University of MadridMadrid, Spain.
[Munoz, Estrada Lourdes] Rey Juan Carlos UniversityMadrid, Spain.
[Manchado, Barderas Rodrigo] Carlos III Health Institute (ISCIII)Madrid, Spain.
[Garcia, Pelaez Alberto] Autonomous University of Madrid, University Hospital La PazMadrid, Spain.
[Medina, Ortega Luis] Autonomous University of MadridMadrid, Spain.
[Roldan, Molina Elena] Hospital Clinico San CarlosMadrid, Spain.
[Fernandez, Solis Guillermo] Carlos III Health Institute (ISCIII)Madrid, Spain.
[Soledad, Garcia Gomez de las Heras] Rey Juan Carlos UniversityMadrid, Spain.
[Acenero, Maria Jesus Fernandez] Autonomous University of MadridMadrid, Spain.
RP del Arco, DC (reprint author), Autonomous University of Madrid, Madrid, Spain.
EM crisdelarco@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2641
EP 2650
DI 10.1007/s12253-020-00863-7
PG 10
ER
PT J
AU Dobi,
Darazs, B
Fodor, E
Cserhati, A
Egyud, Zs
Maraz, A
Laszlo, Sz
Dodd, L
Reisz, Z
Barzo, P
Olah, J
Hideghety, K
AF Dobi, Agnes
Darazs, Barbara
Fodor, Emese
Cserhati, Adrienne
Egyud, Zsofia
Maraz, Aniko
Laszlo, Szilvia
Dodd, Leopold
Reisz, Zita
Barzo, Pal
Olah, Judit
Hideghety, Katalin
TI Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Re-irradiation; Multiformglioblastoma; Glioma
ID Re-irradiation; Multiformglioblastoma; Glioma
AB The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were reirradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm3, and the mean planning target volume (PTV) was 316 cm3, to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.
C1 [Dobi, Agnes] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Darazs, Barbara] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Fodor, Emese] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Cserhati, Adrienne] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Egyud, Zsofia] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Maraz, Aniko] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Laszlo, Szilvia] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Dodd, Leopold] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Reisz, Zita] University of Szeged, Department of Pathology, Allomas utca 1, H-6725 Szeged, Hungary.
[Barzo, Pal] University of Szeged, Department of Neurosurgery, Semmelweis utca 6, H-6725 Szeged, Hungary.
[Olah, Judit] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
[Hideghety, Katalin] University of Szeged, Department of Oncotherapy, Koranyi fasor 12, H-6720 Szeged, Hungary.
RP Dobi, (reprint author), University of Szeged, Department of Oncotherapy, H-6720 Szeged, Hungary.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2651
EP 2658
DI 10.1007/s12253-020-00868-2
PG 8
ER
PT J
AU Hou, R
Liu, Y
Su, Y
Shu, Z
AF Hou, Ruizhi
Liu, Yan
Su, Yanzhuo
Shu, Zhenbo
TI Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FGF14-AS2; RERG; Colorectal cancer
ID FGF14-AS2; RERG; Colorectal cancer
AB Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RTqPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cellbased assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling.
C1 [Hou, Ruizhi] Jilin University, the Third Hospital of Jilin University, Department of Gastrointestinal Colorectal Surgery, 130033 Changchun, Jilin, China.
[Liu, Yan] Jilin University, the Third Hospital of Jilin University, Department of Ultrasound, 130033 Changchun, Jilin, China.
[Su, Yanzhuo] Jilin University, the Third Hospital of Jilin University, Department of Gastrointestinal Colorectal Surgery, 130033 Changchun, Jilin, China.
[Shu, Zhenbo] Jilin University, the Third Hospital of Jilin University, Department of Gastrointestinal Colorectal Surgery, 130033 Changchun, Jilin, China.
RP Shu, Z (reprint author), Jilin University, the Third Hospital of Jilin University, Department of Gastrointestinal Colorectal Surgery, 130033 Changchun, China.
EM shuzhenbobo@outlook.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2659
EP 2667
DI 10.1007/s12253-020-00862-8
PG 9
ER
PT J
AU Lendvai, G
Szekerczes, T
Kontsek, E
Selvam, A
Szakos, A
Schaff, Zs
Bjornstedt, M
Kiss, A
AF Lendvai, Gabor
Szekerczes, Timea
Kontsek, Endre
Selvam, Arun
Szakos, Attila
Schaff, Zsuzsa
Bjornstedt, Mikael
Kiss, Andras
TI The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Methylselenocysteine; Sodium selenite; microRNA expression; Hepatocellular carcinoma; Cholangiocarcinoma; IC50 value
ID Methylselenocysteine; Sodium selenite; microRNA expression; Hepatocellular carcinoma; Cholangiocarcinoma; IC50 value
AB The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC50 values were determined by performing SRB proliferation assays. The results revealed much lower IC50 values for selenite (from 2.7 to 11.3 μM) compared to MSC (from 79.5 to 322.6 μM). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC50. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment,miR-210 in HLF and TFK-1, miR-22, -24, -122, −143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, −199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.
C1 [Lendvai, Gabor] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Szekerczes, Timea] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Kontsek, Endre] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Selvam, Arun] Karolinska University, Department of Pathology, SE-14186 Stockholm, Sweden.
[Szakos, Attila] Karolinska University, Department of Pathology, SE-14186 Stockholm, Sweden.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
[Bjornstedt, Mikael] Karolinska University, Department of Pathology, SE-14186 Stockholm, Sweden.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, Ulloi 93, H-1091 Budapest, Hungary.
RP Kiss, A (reprint author), Semmelweis University, 2nd Department of Pathology, H-1091 Budapest, Hungary.
EM kiss.andras@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2669
EP 2681
DI 10.1007/s12253-020-00870-8
PG 13
ER
PT J
AU Nemeth, Zs
Wijker, W
Lengyel, Zs
Hitre, E
Borbely, K
AF Nemeth, Zsuzsanna
Wijker, Wouter
Lengyel, Zsolt
Hitre, Erika
Borbely, Katalin
TI Metabolic Parameters as Predictors for Progression Free and Overall Survival of Patients with Metastatic Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Standardized added metabolic activity; FDG-PET/CT; Interim; Metastatic colorectal cancer; Overall survival; Progression free survival; Response
ID Standardized added metabolic activity; FDG-PET/CT; Interim; Metastatic colorectal cancer; Overall survival; Progression free survival; Response
AB We tested the prognostic relevance of metabolic parameters and their relative changes in patients with metastatic colorectal cancer (mCRC) treated with monoclonal antibody and chemotherapy. SUVmax (standardized uptake volume), SAM (standardized added metabolic activity) and TLG (total lesion glycolysis) are assessed with 18Ffluorodeoxyglucosepositron emission tomography and computed tomography (FDG-PET/CT) to evaluate total metabolic activity of malignant processes. Our purpose was to investigate the change of glucose metabolism in relation to PFS (progression free survival) and OS (overall survival). Fifty-three patients with mCRC with at least one measurable liver metastasis were included in this prospective, multi-center, early exploratory study. All patients were treated with firstline chemotherapy and targeted therapy. Metabolic parameters, like SUVmax, SAM, normalized SAM (NSAM) and TLG were assessed by FDG-PET/CT, carried out at baseline (scan-1) and after two therapeutic cycle (scan-2). Our results suggested neither SUVmax nor TLG have such prognostic value as NSAM in liver metastases of colorectal cancer. The parameters after the two cycles of chemotherapy proved to be better predictors of the clinical outcome. NSAM after two cycles of treatment has a statistically significant predictive value on OS, while SAM was predictive to the PFS. The follow up normalized SAM after 2 cycles of first line oncotherapy was demonstrated to be useful as prognostic biomarkers for OS in metastatic colorectal cancer. We should introduce this measurement in metastatic colorectal cancer if there is at least one metastasis in the liver.
C1 [Nemeth, Zsuzsanna] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai Osztaly, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Wijker, Wouter] Auxiliis Pharma Ltd, Bokor utca 17, H-1037 Budapest, Hungary.
[Lengyel, Zsolt] Pozitron Diagnosztika Kft, Hunyadi ut 9-11, 1117 Budapest, Hungary.
[Hitre, Erika] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai Osztaly, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
[Borbely, Katalin] National Institute of Oncology, PET/CT Outpatient Department, Rath Gyorgy utca 7-9, 1122 Budapest, Hungary.
RP Nemeth, Zs (reprint author), Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai Osztaly, 1122 Budapest, Hungary.
EM zsnemethzsuzsanna@gmail.com
CR Biasco G, Derenzini E, Ercolani G, Ravaioli M, Pantaleo MA, Brandi G, 2006, Treatment of hepatic metastases from colorectal cancer: many doubts, some certainties. Cancer Treat Rev 32:214– 228. , DOI 10.1016/j.ctrv.2005.12.011
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Bystrom P, Berglund A, Garske U, Jacobsson H, Sundin A, Nygren P, Frodin JE, Glimelius B, 2009, Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-Dglucose positron emission tomography in patients with advanced colorectal cancer. Ann Oncol 20:1057–1061. , DOI 10. 1093/annonc/mdn744
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2683
EP 2691
DI 10.1007/s12253-020-00865-5
PG 9
ER
PT J
AU Barragan-Perez, JE
Altamirano-Vergara, EC
Alvarez-Amado, ED
Garcia-Beristain, CJ
Chico-Ponce-de-Leon, F
Gonzalez-Carranza, V
Juarez-Villegas, L
Murata, Ch
AF Barragan-Perez, Javier Eduardo
Altamirano-Vergara, Enrique Carlos
Alvarez-Amado, Eduardo Daniel
Garcia-Beristain, Carlos Juan
Chico-Ponce-de-Leon, Fernando
Gonzalez-Carranza, Vicente
Juarez-Villegas, Luis
Murata, Chiharu
TI The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Symptomatic interval; Delayed diagnosis; CNS tumors; Survival outcome
ID Symptomatic interval; Delayed diagnosis; CNS tumors; Survival outcome
AB There is no evidence that prolonged pre diagnostic symptomatic intervals (PSI) increases the risk of death in pediatric brain tumors. When investigating the role of time previous research had not controlled for confounding variables or measured the pretreatment interval (PTI). We use the term global delay interval (GDI) to describe the sum of PSI and PTI. The aimof this researchwas to evaluate whether there was a decrease in the probability of survival in children with brain tumors due to a prolonged PSI, PTI and GDI, using a multivariate survival analysis. We retrospective review 127 clinical records labeled with the diagnosis of CNS tumors attended at a specialized pediatric center inMexico City from January 2008 toDecember 2012. Patients with PSI and GDI diagnosed between 3 and 6 months showed statistical lower probability of surviving that those with intervals <3 months even when adjusting for age, sex, localization and tumor grade.When stratified for the place of residency and adjusted for sex, age, localization, grade of tumor, type of surgery and coadjuvant therapy, a GDI between 3 and 6 months showed to be a risk factor for the overall survival of brain tumors compared with an interval < 3 months. When analyzing the interaction, high grade tumors are at more risk of dying when GDI was between 3 and 6 months compared to <3 months. Prolonged PSI and GDI showed to be a potential prognostic factor for survival in CNS tumors, especially in high grade tumors. Future prospective research should measure the PSI, PTI and GDI and adjust for covariates in order to properly infer the effect of time in pediatric brain tumors.
C1 [Barragan-Perez, Javier Eduardo] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurology DepartmentMexico City, Mexico.
[Altamirano-Vergara, Enrique Carlos] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurology DepartmentMexico City, Mexico.
[Alvarez-Amado, Eduardo Daniel] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurology DepartmentMexico City, Mexico.
[Garcia-Beristain, Carlos Juan] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurology DepartmentMexico City, Mexico.
[Chico-Ponce-de-Leon, Fernando] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurosurgery DepartmentMexico City, Mexico.
[Gonzalez-Carranza, Vicente] Hospital Infantil de Mexico Federico Gomez, Pediatric Neurosurgery DepartmentMexico City, Mexico.
[Juarez-Villegas, Luis] Hospital Infantil de Mexico Federico Gomez, Pediatric Oncology DepartmentMexico City, Mexico.
[Murata, Chiharu] Instituto Nacional de Pediatria, Research Methodology DepartmentMexico City, Mexico.
RP Alvarez-Amado, ED (reprint author), Hospital Infantil de Mexico Federico Gomez, Pediatric Neurology Department, Mexico City, Mexico.
EM alvarezamado@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2693
EP 2701
DI 10.1007/s12253-020-00875-3
PG 9
ER
PT J
AU Kabalak, AP
Kizilgoz, D
Kavurgaci, S
Demirci, YN
Yilmaz,
Ak, G
Metintas, S
Metintas, M
Demirag, F
Yilmaz,
AF Kabalak, Akin Pinar
Kizilgoz, Derya
Kavurgaci, Suna
Demirci, Yilmaz Nilgun
Yilmaz, Senay
Ak, Guntulu
Metintas, Selma
Metintas, Muzaffer
Demirag, Funda
Yilmaz, Ulku
TI The Clinical Impact of Re-biopsies in Lung Adenocarcinoma: a Retrospective Multicenter Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Non-small cell lung cancer; Re-biopsy; Targeted therapy
ID Non-small cell lung cancer; Re-biopsy; Targeted therapy
AB If a patient’s cancer progresses while undergoing targeted therapy, a re-biopsy is notmandatory. But when evaluating the benefits and risks on a case-by-case basis (transformation to small cell, assessing for a clinical trial), physicians should inform patients about the possible need for a re-biopsy (5). This was a retrospective and multicentre study. A total of 644 patients with lung adenocarcinoma were reviewed, 625 of whom were ruled eligible. From them, 399 were found to show disease progression, and 126 re-biopsies were performed. Progression status, re-biopsy sites, success of obtaining adequate tissue, molecular patterns after re-biopsy and subsequent treatments were analysed. Survival differences among patients with disease progression were then examined according to re-biopsy status. Overall, 625 patients with adenocarcinoma and a median age of 61.4 were evaluated. Initial tyrosine kinase inhibitor (TKI) usage numbered 37 patients (5.9%). Progression was diagnosed in 399 (63.8%) patients, out of which 26 (31.6%) underwent re-biopsies. The successful number of re-biopsies was 103 (81.7%). No complications were observed after any of the biopsy procedures. Subsequent treatments were changed in 15 patients (11.9%), who began new TKI treatments. Poor performance status was the most common reason for not performing a biopsy (n = 65; 23.8%), followed by the physician’s decision (n = 40; 14.6%). Re-biopsies can demonstrate the new characteristics of a tumour and can detect the activation of pre-existing clones, making possible new treatment opportunities for patients. According to the performance status of the patient and the availability of the progressive lesion, we should increase the rate of re-biopsies before the decision to follow up with the best supportive care.
C1 [Kabalak, Akin Pinar] Ataturk Chest Disease and Thoracic Surgery Teaching and Research Hospital, Department of Chest Disease, 06290 Ankara, Turkey.
[Kizilgoz, Derya] Ataturk Chest Disease and Thoracic Surgery Teaching and Research Hospital, Department of Chest Disease, 06290 Ankara, Turkey.
[Kavurgaci, Suna] Ataturk Chest Disease and Thoracic Surgery Teaching and Research Hospital, Department of Chest Disease, 06290 Ankara, Turkey.
[Demirci, Yilmaz Nilgun] Gazi University School of Medicine, Department of Chest DiseaseAnkara, Turkey.
[Yilmaz, Senay] Eskisehir Osmangazi University, Lung and Pleural Cancers Research and Clinical CenterEskisehir, Turkey.
[Ak, Guntulu] Eskisehir Osmangazi University, Lung and Pleural Cancers Research and Clinical CenterEskisehir, Turkey.
[Metintas, Selma] Eskisehir Osmangazi University, Lung and Pleural Cancers Research and Clinical CenterEskisehir, Turkey.
[Metintas, Muzaffer] Eskisehir Osmangazi University, Lung and Pleural Cancers Research and Clinical CenterEskisehir, Turkey.
[Demirag, Funda] Ankara Ataturk Training and Research Hospital, 1st Pathology ClinicAnkara, Turkey.
[Yilmaz, Ulku] Ataturk Chest Disease and Thoracic Surgery Teaching and Research Hospital, Department of Chest Disease, 06290 Ankara, Turkey.
RP Kabalak, AP (reprint author), Ataturk Chest Disease and Thoracic Surgery Teaching and Research Hospital, Department of Chest Disease, 06290 Ankara, Turkey.
EM pinarakinn@yahoo.com
CR Ettinger DS, Aisner DL, Wood DE, Akerley W, Bauman J, Chang JY et al, 2018 Jul, NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018. J Natl Compr Canc Netw 16(7): 807–821
Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH et al, 2018 Mar, Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 142(3):321–346
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2703
EP 2708
DI 10.1007/s12253-020-00876-2
PG 6
ER
PT J
AU Bernreuther, Ch
Daghigh, F
Moller, K
Hube-Magg, C
Lennartz, M
Lutz, F
Rico, DS
Fraune, Ch
Dum, D
Luebke, A
Eichenauer, T
Moller-Koop, Ch
Schlomm, Th
Wittmer, C
Huland, H
Heinzer, H
Graefen, M
Haese, A
Burandt, E
Tsourlakis, ChM
Clauditz, T
Hoflmayer, D
Izbicki, J
Simon, R
Sauter, G
Minner, S
Steurer, S
Meiners, J
AF Bernreuther, Christian
Daghigh, Ferdous
Moller, Katharina
Hube-Magg, Claudia
Lennartz, Maximilian
Lutz, Florian
Rico, Dwertmann Sebastian
Fraune, Christoph
Dum, David
Luebke, M. Andreas
Eichenauer, Till
Moller-Koop, Christina
Schlomm, Thorsten
Wittmer, Corinna
Huland, Hartwig
Heinzer, Hans
Graefen, Markus
Haese, Alexander
Burandt, Eike
Tsourlakis, Christina Maria
Clauditz, S. Till
Hoflmayer, Doris
Izbicki, R. Jakob
Simon, Ronald
Sauter, Guido
Minner, Sarah
Steurer, Stefan
Meiners, Jan
TI Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SFRP4; Prognosis; Prostate cancer; TMA
ID SFRP4; Prognosis; Prostate cancer; TMA
AB Secreted frizzled-related protein 4 (SFRP4) controlsWNT signaling and is thought to play a role for tumor aggressiveness. Here, we analyzed a tissue microarray containing 11,152 prostate cancers with pathological, clinical and molecular data by immunohistochemistry. SFRP4 expression was higher in cancer than in non-neoplastic acinar cells. SFRP4 staining was seen in 64.9%of tumors and classified as weak in 33.2%, moderate in 23.9% and strong in 7.8% of cancers. SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p < 0.0001 each), lymph node metastasis (p = 0.0002), and a positive surgical margin (p = 0.0017). SFRP4 positivity was markedly more frequent in ERG positive (77.4%) than in ERG negative cancers (57.4% p < 0.0001). Subset analyses in 2725 cancers with and 3592 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. In a multivariate analysis including various postoperative and prognostic clinico-pathological features, SFRP4 protein expression emerged as an independent prognostic parameter in ERG negative cancers. SFRP4 immunostaining was significantly linked with 10 of 11 previously analyzed chromosomal deletions (p < 0.05 each). In conclusion, high SFRP4 immunostaining is associated with poor prognosis and genomic instability in ERG negative prostate cancers.
C1 [Bernreuther, Christian] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Daghigh, Ferdous] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Moller, Katharina] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Hube-Magg, Claudia] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Lennartz, Maximilian] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Lutz, Florian] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Rico, Dwertmann Sebastian] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Fraune, Christoph] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Dum, David] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Luebke, M. Andreas] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Eichenauer, Till] University Medical Center Hamburg-Eppendorf, Department of UrologyHamburg, Germany.
[Moller-Koop, Christina] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Schlomm, Thorsten] Charite-Universitatsmedizin Berlin, Department of UrologyBerlin, Germany.
[Wittmer, Corinna] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Huland, Hartwig] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Heinzer, Hans] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Graefen, Markus] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Haese, Alexander] Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburg, Germany.
[Burandt, Eike] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Tsourlakis, Christina Maria] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Clauditz, S. Till] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Hoflmayer, Doris] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Izbicki, R. Jakob] University Medical Center Hamburg-Eppendorf, General, Visceral and Thoracic Surgery DepartmentHamburg, Germany.
[Simon, Ronald] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Sauter, Guido] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Minner, Sarah] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Steurer, Stefan] University Medical Center Hamburg Eppendorf, Pathology, Martinistr, 52, 20246 Hamburg, Germany.
[Meiners, Jan] University Medical Center Hamburg-Eppendorf, General, Visceral and Thoracic Surgery DepartmentHamburg, Germany.
RP Simon, R (reprint author), University Medical Center Hamburg Eppendorf, Pathology, 20246 Hamburg, Germany.
EM R.Simon@uke.de
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2709
EP 2722
DI 10.1007/s12253-020-00861-9
PG 14
ER
PT J
AU Uzelac, B
Krivokuca, A
Brankovic-Magic, M
Magic, Z
Susnjar, S
Milovanovic, Z
Supic, G
AF Uzelac, Bojana
Krivokuca, Ana
Brankovic-Magic, Mirjana
Magic, Zvonko
Susnjar, Snezana
Milovanovic, Zorka
Supic, Gordana
TI Expression of SIRT1, SIRT3 and SIRT6 Genes for Predicting Survival in Triple-Negative and Hormone Receptor-Positive Subtypes of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Sirtuins; Gene expression; Triple-negative breast Cancer; Hormone receptor-positive breast Cancer; Survival
ID Sirtuins; Gene expression; Triple-negative breast Cancer; Hormone receptor-positive breast Cancer; Survival
AB Triple-negative breast cancer (TNBC) is characterized by aggressive phenotype and a poorer prognosis compared to the estrogen and progesterone receptor positive, Her2 negative (ER + PR + Her2-) breast cancer. Increasing evidence suggests that sirtuins, a family of histone deacetylases, could have an important role in aggressiveness of TNBC’s. The current study evaluated the potential clinical relevance of SIRT1, SIRT3 and SIRT6 gene expressions in two prognostically distinctive subtypes of breast cancer, the most aggressive TNBC and the least aggressive ER + PR + Her2- tumors. Total RNAs were isolated from 48 TNBC and 63 ER + PR + Her2- tumor samples. Relative gene expression was determined by SYBR Green RT-PCR and delta-delta Ct method, normalized to GAPDH.Mean gene expression of both SIRT1 and SIRT3 was significantly lower in the TNBC compared to ER + PR + Her2- tumors (p = 0.0001). Low SIRT1 and SIRT6 expressions associatedwith worse overall survival in ER + PR + Her2- patients (p = 0.039, p = 0.006, respectively), while TNBC patients with high SIRT1 tend to have a poor prognosis (p = 0.057). In contrast, high expression of SIRT3 in TNBC patients associated with higher histological grade (p = 0.027) and worse overall survival (p = 0.039). The Cox regression analysis revealed that low SIRT1 expression could be an independent prognostic marker of poor survival in ER + PR + Her2- breast cancers (HR = 11.765, 95% CI:1.234–100, p = 0.033). Observed differential expression of SIRT1, SIRT3 and SIRT6 genes in TNBC and ER + PR + Her2- subtypes, with opposite effects on patients’ survival, suggests context-dependent mechanisms underlying aggressiveness of breast cancer. Further investigations are necessary to evaluate sirtuins as potential biomarkers and therapeutic targets in breast cancer.
C1 [Uzelac, Bojana] Military Medical Academy, Institute for Medical Research, Crnotravska 17, 11 000 Belgrade, Serbia.
[Krivokuca, Ana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Brankovic-Magic, Mirjana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Magic, Zvonko] Military Medical Academy, Institute for Medical Research, Crnotravska 17, 11 000 Belgrade, Serbia.
[Susnjar, Snezana] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Milovanovic, Zorka] Institute of Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
[Supic, Gordana] Military Medical Academy, Institute for Medical Research, Crnotravska 17, 11 000 Belgrade, Serbia.
RP Supic, G (reprint author), Military Medical Academy, Institute for Medical Research, 11 000 Belgrade, Serbia.
EM gogasupic@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2723
EP 2731
DI 10.1007/s12253-020-00873-5
PG 9
ER
PT J
AU Ozkan, SH
Ugurlu, UM
Yumuk, FP
Kaya, H
AF Ozkan, Sahin Hulya
Ugurlu, Umit Mustafa
Yumuk, Fulden Perran
Kaya, Handan
TI Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Triple negative breast cancer; Tumor infiltrating lymphocytes; Tumor associated macrophages; PD-L1; Fork head box protein 3; Immunohistochemistry
ID Triple negative breast cancer; Tumor infiltrating lymphocytes; Tumor associated macrophages; PD-L1; Fork head box protein 3; Immunohistochemistry
AB Tumor immune microenvironment (TIME) is a significant prognostic parameter for triple negative breast carcinomas (TNBC) due to being a target for immunotherapeutic agents and its essential role during the cancer immunoediting process. In this study, CD8, FOXP3, CD163, PD-L1/SP142 and PD-L1/SP263 antibodies were examined in a sample of 51 TNBC cases. Patients who received neoadjuvant therapy were excluded. CD8, FOXP3 and CD163 antibodies were evaluated separately in intratumoral area (ITA) and tumor stroma (TS). PD-L1 status was also examined in tumor cells (TC) and immune cells (IC) using both SP142 and SP263 antibodies. In multivariate Cox regressions, the only antibody that was found to be significantly associated with survival was SP142. SP142-positivity in TC and IC was related to increased overall survival. Higher CD163 expression in ITA and SP263-positivity in IC were associated with younger age. Lymphatic/angioinvasion was more frequent in cases with negative/ low CD8 and FOXP3 expressions. Moreover, metastatic axillary lymph node(s) was associated with negative/low FOXP3 expression in TS. CD8, FOXP3, CD163, SP142 and SP263 expressions were positively correlated with each other, except a mild discordance caused by CD163 in ITA. Although PD-L1 status with both SP142 and SP263 antibodies were concordant in the majority of cases, 33.3% and 13.7% of the cases showed SP142-negative/SP263-positive pattern in TC and IC respectively. In conclusion, we suggest that composition, density and localization of the immune cells and the check point molecules are important prognostic parameters in TNBC. Immunohistochemistry can be used as an accessible and less expensive tool to demonstrate TIME.
C1 [Ozkan, Sahin Hulya] Marmara University, School of Medicine, Department of PathologyIstanbul, Turkey.
[Ugurlu, Umit Mustafa] Marmara University, School of Medicine, Department of General SurgeryIstanbul, Turkey.
[Yumuk, Fulden Perran] Marmara University School of Medicine, Department of Medical OncologyIstanbul, Turkey.
[Kaya, Handan] Marmara University, School of Medicine, Department of PathologyIstanbul, Turkey.
RP Ozkan, SH (reprint author), Marmara University, School of Medicine, Department of Pathology, Istanbul, Turkey.
EM drhulyasahin@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2733
EP 2745
DI 10.1007/s12253-020-00874-4
PG 13
ER
PT J
AU Sejben, A
Koszo, R
Kahan, Zs
Cserni, G
Zombori, T
AF Sejben, Anita
Koszo, Renata
Kahan, Zsuzsanna
Cserni, Gabor
Zombori, Tamas
TI Examination of Tumor Regression Grading Systems in Breast Cancer Patients Who Received Neoadjuvant Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; Neoadjuvant therapy; Regression pattern; Grading systems; Residual cancer burden
ID Breast cancer; Neoadjuvant therapy; Regression pattern; Grading systems; Residual cancer burden
AB Neoadjuvant therapy is a common formof treatment in locally advanced breast cancer (LABC) patients. Besides some guidelines for grading regression, a standardized general scheme is not yet available. The aim of our study was to compare the prognostic impact of different regression grading systems, namely the TR/NR, Chevallier, Sataloff, Denkert-Sinn, Miller-Payne, NSABPB18, Residual Disease in Breast and Nodes and Residual Cancer Burden (RCB) on disease-free (DFS) and overall survival (OS). Data of 746 breast cancer patients treated in neoadjuvant setting between 1999 and 2019 have been included. The different regression grades and follow-up data were collected from medical charts. Statistical analysis included the Kaplan-Meier method, log-rank test and multivariate Cox regression. The average patient age was 55 years. The DFS and OS estimates of patients with complete pathological regression and residual in situ carcinoma have been significantly more favorable than those having partial regression or no signs of regression (pDFS<0.001, pOS < 0.001). Significant differences were found between DFS estimates of classes with partial regression and without regression defined by RCB. Concerning DFS estimates, the RCB classification (p = 0.019), while regarding OS data the y-stage (p = 0.011) and the nodal status (ypN; p = 0.045) were significant prognosticators by multivariate Cox regression. Regression grading systems help the evaluation of regression in LABC patients treated with neoadjuvant therapy. Of the several grading systems compared, the RCB classification makes the best distinction between the outcomes of the different classes, therefore we recommend the inclusion of RCB into the histopathological findings.
C1 [Sejben, Anita] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
[Koszo, Renata] University of Szeged, Department of OncotherapySzeged, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
[Zombori, Tamas] University of Szeged, Department of Pathology, Allomas u. 1, 6725 Szeged, Hungary.
RP Sejben, A (reprint author), University of Szeged, Department of Pathology, 6725 Szeged, Hungary.
EM sejben.anita@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2747
EP 2754
DI 10.1007/s12253-020-00867-3
PG 8
ER
PT J
AU Zengin, M
Benek, S
AF Zengin, Mehmet
Benek, Suat
TI The Proportion of Tumour-Stroma in Metastatic Lymph Nodes is An Accurately Prognostic Indicator of Poor Survival for Advanced-Stage Colon Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colon cancers; Proportion of tumour-stroma; Pathology; Prognostic markers; Stage III-IV
ID Colon cancers; Proportion of tumour-stroma; Pathology; Prognostic markers; Stage III-IV
AB The importance of tumour microenvironment in tumour behaviour has now become clearer. This study aimed to determine the prognostic effect of the proportion of tumour-stroma (PTS) in metastatic lymph nodes of advanced-stage colon cancers (CCs). We investigated PTS in positive lymph nodes of stage III-IV CC patients who underwent surgical treatment between 2004 and 2014. We used a standard approach in methodology. PTS was significantly associated with prognostic factors in the metastatic lymph nodes (perineural invasion [p = 0.031], lymphatic invasion [p = 0.032], invasive margin [p = 0.043], advanced pT [p = 0.020], and margin involvement [p = 0.034]). In addition, the correlations between PTS estimates (R = 0.704 to 0.617, p < 0.001), the reproducibility of the research (Κappa = 0.72–0.68) and the usefulness of the cut-off value (ROC: 50.33%; AUC = 0.752 [0.667–0.857]) were successful. In univariate analysis, 5-year survival was poor for RFS (p < 0.001), OS (p = 0.001) and LR (p = 0.013) in high PTS patients. Multivariate analysis confirmed that high PTS was an independent worse parameter for RFS (HR = 1.32, 95% CI: 1.17–2.55, p = 0.001) and OS (HR = 1.37, 95% CI: 1.25–1 - 2.56, p = 0.009). In this study, we showed that high PTS inmetastatic lymph nodes was a successful prognosticmarker for advanced-stage CCs. Also, the standard approach we used for the methodology was successful.
C1 [Zengin, Mehmet] Kirikkale University, Department of PathologyKirikkale, Turkey.
[Benek, Suat] Beylikduzu State Hospital, Department of General SurgeryIstanbul, Turkey.
RP Zengin, M (reprint author), Kirikkale University, Department of Pathology, Kirikkale, Turkey.
EM mz1379@hotmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2755
EP 2764
DI 10.1007/s12253-020-00877-1
PG 10
ER
PT J
AU Csernus, B
Timar, B
Fulop, Zs
Matolcsy, A
AF Csernus, Balazs
Timar, Botond
Fulop, Zsolt
Matolcsy, Andras
TI Grade I, II and III Follicular Lymphomas Express Ig VH Genes with Different Patterns of Somatic Mutation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Follicular lymphoma|; Immunoglobulin gene; Somaticmutation; Clonal evolution
ID Follicular lymphoma|; Immunoglobulin gene; Somaticmutation; Clonal evolution
AB Follicular lymphoma (FL) is an indolent, B-cell, non-Hodgkin’s lymphoma with varying cytological appearance and clinical behavior. The genetic hallmark of FL is the t(14;18) translocation, and as a germinal center derived entity it is also characterized by somatic hypermutation of the immunoglobulin heavy chain (IgH) gene. In an attempt to correlate thismolecular signature with the cytological grading of FL, we have analyzed the IgH variable (IgVH), regions in all cytological grades of FL. Four FL cases showing t(14;18) translocation were classified into grade I-III categories according to the current WHO guidelines. The IgVH gene segments were PCR-amplified, sequenced, and compared to their respective germline IgVH sequences. The neoplastic cells of grade I and II FLs revealed clonally related, but highly divergent IgVH gene sequences indicating the ongoing nature of somatic hypermutation. Grade III FL also showed extensive presence of somatic hypermutation, but these mutations were not associated with intraclonal divergence. Thus, these results suggest that grade I-II and grade III FL may represent different biological entities. The presence of ongoing somatic hypermutation of IgVH sequences in grade I and II FLs is compatible with direct follicular origin of these tumor cells, contrasting the homogenous, stable clones of grade III FL resembling a post-follicular stage of B-cell development. Our findings demonstrate that contrary to the three tiered cytological grading, molecular features of IgH genes classify FL into two distinct subcategories. These studies also suggest that with progression FL gains post-follicular– like molecular features and becomes independent of the germinal center microenvironment.
C1 [Csernus, Balazs] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Fulop, Zsolt] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
[Matolcsy, Andras] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Ulloi ut 26, 1085 Budapest, Hungary.
RP Matolcsy, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
EM matolcsy.andras@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2765
EP 2772
DI 10.1007/s12253-020-00843-x
PG 8
ER
PT J
AU Nagy, N
Reis, H
Hadaschik, B
Niedworok, Ch
Modos, O
Szendroi, A
Biro, K
Hager, Th
Herold, Th
Ablat, J
Black, P
Okon, K
Tolkach, Y
Csizmarik, A
Olah, Cs
Keresztes, D
Bremmer, F
Gaisa, N
Kriegsmann, J
Kovalszky, I
Kiss, A
Timar, J
Szasz, AM
Rink, M
Fisch, M
Nyirady, P
Szarvas, T
AF Nagy, Nikolett
Reis, Henning
Hadaschik, Boris
Niedworok, Christian
Modos, Orsolya
Szendroi, Attila
Biro, Krisztina
Hager, Thomas
Herold, Thomas
Ablat, Jason
Black, C. Peter
Okon, Krzysztof
Tolkach, Yuri
Csizmarik, Anita
Olah, Csilla
Keresztes, David
Bremmer, Felix
Gaisa, T. Nadine
Kriegsmann, Joerg
Kovalszky, Ilona
Kiss, Andras
Timar, Jozsef
Szasz, Attila Marcell
Rink, Michael
Fisch, Margit
Nyirady, Peter
Szarvas, Tibor
TI Prevalence of APC and PTEN Alterations in Urachal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Urachal cancer; Colorectal cancer; Molecular genetics; Mutation; APC; ß-catenin
ID Urachal cancer; Colorectal cancer; Molecular genetics; Mutation; APC; ß-catenin
AB Urachal carcinoma (UrC) is a rare tumor with remarkable histological and molecular similarities to colorectal cancer (CRC). Adenomatous polyposis coli (APC) is the most frequently affected gene in CRC, but the prevalence and significance of its alterations in UrC is poorly understood. In addition, loss of phosphatase and tensin homologue (PTEN) was shown to be associated with therapy resistance in CRC. Our primary aim was to assess specific genetic alterations including APC and PTEN in a large series of UrC samples in order to identify clinically significant genomic alterations. We analyzed a total of 40 UrC cases. Targeted 5-gene (APC, PTEN, DICER1, PRKAR1A, TSHR, WRN) panel sequencing was performed on the Illumina MiSeq platform(n = 34). In addition, ß-catenin (n = 38) and PTEN (n = 30) expressionswere assessed by immunohistochemistry. APC and PTEN genes were affected in 15% (5/34) and 6% (2/34) of cases. Two of five APC alterations (p.Y1075*, p.K1199*) were truncating pathogenic mutations. One of the two PTEN variants was a pathogenic frameshift insertion (p.C211fs). In 29% (11/38) of samples, at least some weak nuclear ß-catenin immunostaining was detected and PTEN loss was observed in 20% (6/30) of samples. The low prevalence of APC mutations in UrC represents a characteristic difference to CRC. Based on APC and ß-catenin results, the Wnt pathway seems to be rarely affected in UrC. Considering the formerly described involvement of PTEN protein loss in anti-EGFR therapy-resistance its immunohistochemical testing may have therapeutic relevance.
C1 [Nagy, Nikolett] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Reis, Henning] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, 45147 Essen, Germany.
[Hadaschik, Boris] University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
[Niedworok, Christian] University of Duisburg-Essen, Department of Urology, 45147 Essen, Germany.
[Modos, Orsolya] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Szendroi, Attila] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Biro, Krisztina] National Institute of Oncology, 1122 Budapest, Hungary.
[Hager, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, 45147 Essen, Germany.
[Herold, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of Pathology, 45147 Essen, Germany.
[Ablat, Jason] University of British Columbia, Vancouver Prostate Centre & Department of Urologic Science, V6H 3Z6 Vancouver, Canada.
[Black, C. Peter] University of British Columbia, Vancouver Prostate Centre & Department of Urologic Science, V6H 3Z6 Vancouver, Canada.
[Okon, Krzysztof] Jagiellonian University, Department of Pathomorphology, 30252 Cracow, Poland.
[Tolkach, Yuri] University of Bonn, Institute of Pathology, 53113 Bonn, Germany.
[Csizmarik, Anita] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Olah, Csilla] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Keresztes, David] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Bremmer, Felix] University of Gottingen, Institute of Pathology, 37073 Gottingen, Germany.
[Gaisa, T. Nadine] Medical Faculty of the Technical University of Aachen, Department of Pathology, 52074 Aachen, Germany.
[Kriegsmann, Joerg] Center for Histology, Cytology and Molecular Diagnostics Trier, 54296 Trier, Germany.
[Kovalszky, Ilona] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of Pathology, 1091 Budapest, Hungary.
[Szasz, Attila Marcell] Semmelweis University, Department of Oncology, 1083 Budapest, Hungary.
[Rink, Michael] University Medical Center Hamburg-Eppendorf, Department of Urology, 20246 Hamburg, Germany.
[Fisch, Margit] University Medical Center Hamburg-Eppendorf, Department of Urology, 20246 Hamburg, Germany.
[Nyirady, Peter] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
[Szarvas, Tibor] Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
RP Szarvas, T (reprint author), Semmelweis University, Department of Urology, 1082 Budapest, Hungary.
EM sztibusz@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2773
EP 2781
DI 10.1007/s12253-020-00872-6
PG 9
ER
PT J
AU Major, T
Gindele, R
Szabo, Zs
Kis, Zs
Bora, L
Joni, N
Bardossy, P
Racz, T
Bereczky, Zs
AF Major, Tamas
Gindele, Reka
Szabo, Zsuzsanna
Kis, Zsuzsanna
Bora, Laszlo
Joni, Natalia
Bardossy, Peter
Racz, Tamas
Bereczky, Zsuzsanna
TI The Stratified Population Screening of Hereditary Hemorrhagic Telangiectasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hereditary hemorrhagic telangiectasia; Prevalence; Stratified screening; ACVRL1; ENG; Founder effect
ID Hereditary hemorrhagic telangiectasia; Prevalence; Stratified screening; ACVRL1; ENG; Founder effect
AB Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a worldwide prevalence of 1:5000–1:10000. We introduce our algorithm for the stratified population screening of HHT. Probands are selected from the consecutive hospital database review for HHT (I7800) and recurrent epistaxis (R0400) and the review of patient records referred by family practitioners. A proportion of probands might be de novo diagnosed with HHT in the 10-year study period. The checkup of probands consists of physical examination, arteriovenous malformation exploration and genetic testing (ACVRL1 and ENG sequence analysis). The family screening of HHT consists of physical examination and screening for the family-specific mutation of each at-risk individual, and furthermore, arteriovenous malformation exploration in individuals with suspected/definite HHT and/or carrying the mutation. Twenty-five definite HHT patients were explored: 7 of them by the I7800 review, 1 by the R0400 review, 3 were de novo diagnosed, and the remaining 14 were explored by the systematic family screening. Considering the 20 patients alive at the end of the study period and the unavailable 5 potential HHT patients and 12 at-risk family members, the HHT prevalence is estimated to be 1:6090–1:11267 in our study area, implying our algorithm’s effectivity in the stratified population screening of HHT.
C1 [Major, Tamas] B-A-Z County Central Hospital and University Teaching Hospital, Department of Otolaryngology and Head and Neck Surgery, Szentpeteri kapu 72-76, H-3526 Miskolc, Hungary.
[Gindele, Reka] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Szabo, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
[Kis, Zsuzsanna] Ferenc Markhot County Hospital, Department of Radiology, Szechenyi u. 27-29, H-3300 Eger, Hungary.
[Bora, Laszlo] Szent Lazar County Hospital, Department of Radiology, Fuleki ut 54-56, H-3100 Salgotarjan, Hungary.
[Joni, Natalia] Ferenc Markhot County Hospital, Department of Internal Medicine, Szechenyi u. 27-29, H-3300 Eger, Hungary.
[Bardossy, Peter] Hungarian Heraldry and Genealogical Society, Becsi Kapu ter 2-4, H-1014 Budapest, Hungary.
[Racz, Tamas] Ferenc Markhot County Hospital, Department of Otorhinolaryngology, Szechenyi u. 27-29, H-3300 Eger, Hungary.
[Bereczky, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
RP Major, T (reprint author), B-A-Z County Central Hospital and University Teaching Hospital, Department of Otolaryngology and Head and Neck Surgery, H-3526 Miskolc, Hungary.
EM majordoki2@gmail.com
CR Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H, 2000, Diagnostic criteria for hereditary hemorrhagic telangiectasia, Rendu-Osler-weber syndrome). Am J Med Genet 91:66–67
Sharathkumar AA, Shapiro A, 2008, Hereditary haemorrhagic telangiectasia. Haemophilia 14:1269–1280. , DOI 10.1111/j. 1365-2516.2008.01774.x
University of Utah, Department of Pathology. HHT Mutation Database. http://arup.utah.edu/database/HHT/. Accessed December 3rd, 2018
Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, Spears J, Brown DH, Buscarini E, Chesnutt MS, Cottin V, Ganguly A, Gossage JR, Guttmacher AE, Hyland RH, Kennedy SJ, Korzenik J, Mager JJ, Ozanne AP, Piccirillo JF, Picus D, Plauchu H, Porteous ME, Pyeritz RE, Ross DA, Sabba C, Swanson K, Terry P, Wallace MC, Westermann CJ, White RI, Young LH, Zarrabeitia R, 2011, International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 48:73–87. , DOI 10.1136/jmg. 2009.069013
Bayrak-Toydemir P, McDonald J,Markewitz B, Lewin S,Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R, 2006, Genotypephenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet 140: 463–470. , DOI 10.1002/ajmg.a.31101
Lesca G, Genin E, Blachier C, Olivieri C, Coulet F, Brunet G, Dupuis-Girod S, Buscarini E, Soubrier F, Calender A, Danesino C, Giraud S, Plauchu H, 2008, Hereditary hemorrhagic telangiectasia: evidence for regional founder effects of ACVRL1 mutations in French and Italian patients. Eur J Hum Genet 16:742–749. , DOI 10.1038/ejhg.2008.3
Brusgaard K, Kjeldsen AD, Poulsen L, Moss H, Vase P, Rasmussen K, Kruse TA, HorderM(2004)Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet 66:556–561. , DOI 10.1111/j.1399-0004.2004.00341.x
Heimdal K, Dalhus B, Rodningen OK, Kroken M, Eiklid K, Dheyauldeen S, Roysland T, Andersen R, Kulseth MA, 2015, Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in ACVRL1. Clin Genet 89:182–186. , DOI 10.1111/cge.12612
Major T, Gindele R, Szabo Z, Alef T, Thiele B, Bora L, Kis Z, Bardossy P, Racz T, Havacs I, Bereczky Z, 2016, Evidence for the founder effect of a novel ACVRL1 splice-site mutation in Hungarian hereditary hemorrhagic telangiectasia families. Clin Genet 90:466–467
Torring PM, Brusgaard K, Ousager LB, Andersen PE, Kjeldsen AD, 2014, National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet 86:123–133. , DOI 10.1111/cge.12269, , DOI 10.1111/cge.12806
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2783
EP 2788
DI 10.1007/s12253-019-00602-7
PG 6
ER
PT J
AU Sangam, K
Kumar, Y
Walker Minz, R
Varma, N
Varma, S
Anand, Sh
AF Sangam, Kumar
Kumar, Yashwant
Walker Minz, Ranjana
Varma, Neelam
Varma, Subhash
Anand, Shashi
TI Patients with Plasma Cell Disorders Have High EBV DNA in Peripheral Blood than the General Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Epstein - Barr virus; Plasma cell disorders; Quantitative real time PCR; Immunocompetent
ID Epstein - Barr virus; Plasma cell disorders; Quantitative real time PCR; Immunocompetent
AB Epstein-Barr virus (EBV) is involved in the development of a wide range of B cell lympho-proliferative disorders. Its association with plasma cell disorders (PCD) however is not clear, especially in immunocompetent patients. To explore any relationship, 39 patients of suspected PCD with positive M-band on electrophoresis and 50 healthy controls were enrolled. EBV DNA in peripheral blood was quantified using quantitative Real Time Polymerase Chain Reaction (qPCR). Of 39 patients, 15 (38.5%) had EBV DNA compared to 8/50 (16%) controls (p = 0.0008). The mean viral copy number was found to be significantly high in patients compared to controls (1.8 × 105; range = 2.6 × 103–7.6 × 105 copies/ml and 1.7 × 104; range = 7.0 × 102–6.1 × 104 copies/ml respectively; p = 0.003). This is the first study, which characterizes the frequency of EBV in circulation in patients of PCD. The significance of increased prevalence of circulating EBV and a higher viral load in our immunocompetent patients however, needs further evaluation.
C1 [Sangam, Kumar] Post Graduate Institute of Medical Education & Research, Department of ImmunopathologyChandigarh, India.
[Kumar, Yashwant] Post Graduate Institute of Medical Education & Research, Department of ImmunopathologyChandigarh, India.
[Walker Minz, Ranjana] Post Graduate Institute of Medical Education & Research, Department of ImmunopathologyChandigarh, India.
[Varma, Neelam] Post Graduate Institute of Medical Education & Research, Department of ImmunopathologyChandigarh, India.
[Varma, Subhash] Post Graduate Institute of Medical Education & Research, Department of Internal MedicineChandigarh, India.
[Anand, Shashi] Post Graduate Institute of Medical Education & Research, Department of ImmunopathologyChandigarh, India.
RP Kumar, Y (reprint author), Post Graduate Institute of Medical Education & Research, Department of Immunopathology, Chandigarh, India.
EM dryashwant@ymail.com
CR Babel N, Schwarzmann F, Pruss A, Volk HD, Reinke P, 2004, Monoclonal gammopathy of undetermined significance, MGUS, is associated with an increased frequency of Epstein-Barr virus, EBV, latently infected B lymphocytes in long-term renal transplant patients. Transplant Proc 36:2679–2682
Giordano M, Santangelo L, Scarasciulli ML, Calvario A, Miragliotta G, Giordano P, Cecinati V, 2014, Monoclonal gammopathy of undetermined significance in pediatric kidney transplant: a possible role of Epstein-Barr virus. Pediatr Transplant 18:42–46
Hsieh AT, Ho CL, Chen YC et al, 2002, Epstein-Barr virus and lymphoid hematological disorders. ZonghuaYi Xue Za Zhi, Taipei, 65:119–123
Chang ST, Liao YL, Lu CL, Chuang SS, Li CY, 2007, Plasmablastic cytomorphologic features in plasma cell neoplasms in immunocompetent patients are significantly associated with EBV. Am J Clin Pathol 128(2):339–344
Nael A, Wu WW, Siddiqi I et al Epstein - Barr virus association with. Plasma Cell Neoplasms Histol Histopath 2018Nov 19:18066. , DOI 10.14670/HH-18-066. [Epub ahead of print]
Lin JC,Wan gWY, Chen KYet al, 2004, Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 350:2461–2470
Zhang Y, Zhao H, He X, Zheng S, Wang T, Yan D, Sun J, Lu X, Wen J, Lau WY, 2012, Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation. Sci China Life Sci 55:735–743
Thorley-Lawson DA, Babcock GJ, 1999, A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Sci 65(14):1433–1453
Sasaki S, Hashimoto K, Nakatsuka S, Hasegawa M, Nakano T, Nagata S, Kanakura Y, Hayashi N, 2011, Plasmablastic extramedullary plasmacytoma associated with Epstein-Barr virus arising in an immunocompetent patient with multiple myeloma. Intern Med 50:2615–2620
Chen H, Hutt-Fletcher L, Cao L, Hayward SD, 2003, A positive autoregulatory loop of lmp1 expression and stat activation in epithelial cells latently infected with Epstein-Barr virus. J Virol 77:4139–4148
Laichalk LL, Thorley-Lawson DA, 2005, Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol 79:1296–1307
SadeghianMH, Ayatollahi H, Keramati MR(2011, The association of Epstein-Barr virus infection with multiple myeloma. Ind J Pathol Microbiol 54:720–724
Tomita Y, Ohsawa M, Hashimoto M, 1998, Plasmacytoma of the gastrointestinal tract in Korea: higher incidence than in Japan and Epstein-Barr virus association. Oncology 55(1):27–32
Hoebeeck J, Speleman F, Vandesompele J, 2007, Real-time quantitative PCR as an alternative to southern blot or fluorescence in situ hybridization for detection of gene copy number changes. Methods Mol Biol 353:205–226
Lunemann JD, Tackenberg B, Stein A,Wandinger KP, Oertel WH, Wagner HJ, Munz C, Meisel H, Sommer N, Zipp F, 2010, Dysregulated Epstein-Barr virus infection in patients with CIDP. J Neuroimmunol 218(1–2):107–111
Chang YT, Liu HN, Wong CK, Chow KC, Chen KY, 1997, Detection of Epstein-Barr virus in primary cutaneous amyloidosis. Br J Dermatol 136(6):823–826
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2789
EP 2794
DI 10.1007/s12253-019-00640-1
PG 6
ER
PT J
AU Nassereddine, H
Sannier, A
Brosseau, S
Rodier, JM
Khalil, A
Msika, S
Danel, C
Couvelard, A
Theou-Anton, N
Cazes, A
AF Nassereddine, Hussein
Sannier, Aurelie
Brosseau, Solenn
Rodier, Jean-Michel
Khalil, Antoine
Msika, Simon
Danel, Claire
Couvelard, Anne
Theou-Anton, Nathalie
Cazes, Aurelie
TI Clinicopathological and Molecular Study of Peritoneal Carcinomatosis Associated with Non-Small Cell Lung Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Peritoneal carcinomatosis; Non-small cell lung carcinoma; NSCLC; Massively-parallel sequencing; Molecular pathology
ID Peritoneal carcinomatosis; Non-small cell lung carcinoma; NSCLC; Massively-parallel sequencing; Molecular pathology
AB To retrospectively characterize the molecular features of Non-Small Cell Lung Carcinomas (NSCLC) with peritoneal carcinomatosis (PC), clinicopathological data of 12 patients diagnosed with NSCLC and PC between 2007 and 2016 were collected. Immunohistochemistry and Next Generation Sequencing (NGS) were performed on cases with available material. PC was the initial presentation of NSCLC in 17% of the cases. Overall, patients with PC displayed a poor median survival of 12 weeks. Histology was adenocarcinoma in 11 cases. 37.5% of cases showed PD-L1 immunostaining positivity (50% cut-off). ALK and ROS1 immunostainings were negative. Using NGS, we identified 17 molecular alterations in 9 genes (TP53, KRAS, STK11, BRAF, EGFR, DDR2, ERBB4, SMAD4, CTNNB1) in 88.9% of adenocarcinomas. To the best of our knowledge, 5 of these variants are not referenced in the literature. In conclusion, PC might be the initial presentation of NSCLC. Molecular profiling of our cases did not find any effective targetable alteration, except from high PD-L1 expression.
C1 [Nassereddine, Hussein] Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologieParis, France.
[Sannier, Aurelie] Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologieParis, France.
[Brosseau, Solenn] University of Paris 5Paris, France.
[Rodier, Jean-Michel] APHP, Hopital Bichat-Claude Bernard, service d’OncologieParis, France.
[Khalil, Antoine] University of Paris 5Paris, France.
[Msika, Simon] University of Paris 5Paris, France.
[Danel, Claire] Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologieParis, France.
[Couvelard, Anne] Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologieParis, France.
[Theou-Anton, Nathalie] APHP, Hopital Bichat-Claude Bernard, laboratoire de GenetiqueParis, France.
[Cazes, Aurelie] Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologieParis, France.
RP Nassereddine, H (reprint author), Assistance Publique – Hopitaux de Paris, Hopital Bichat-Claude Bernard, departement de pathologie, Paris, France.
EM hussein.nassereddine@hotmail.com
CR Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, 2015, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
Satoh H, Ishikawa H, Yamashita YT, Kurishima K, Ohtsuka M, Sekizawa K, 2001, Peritoneal carcinomatosis in lung cancer patients. Oncol Rep 8(6):1305–1307
Patil T, Aisner DL, Noonan SA, Bunn PA, Purcell WT, Carr LL, Camidge DR, Doebele RC, 2016, Malignant pleural disease is highly associated with subsequent peritoneal metastasis in patients with stage IV non-small cell lung cancer independent of oncogene status. Lung Cancer 96:27–32
Sereno M, Rodriguez-Esteban I, Gomez-Raposo C, Merino M, Lopez-Gomez M, Zambrana F et al, 2013, Lung cancer and peritoneal carcinomatosis. Oncol Lett 6(3):705–708
Su H-T, Tsai C-M, Perng R-P, 2008, Peritoneal carcinomatosis in lung cancer. Respirol 13(3):465–467
McNeill PM, Wagman LD, Neifeld JP, 1987, Small bowel metastases from primary carcinoma of the lung. Cancer 59(8):1486–1489
Okami J, Taniguchi K, Higashiyama M, Maeda J, Oda K, Orita N, Koizumi K, Kodama K, Kato K, 2007, Prognostic factors for gefitinib-treated postoperative recurrence in non-small cell lung cancer. Oncology 72(3–4):234–242
Klughammer B, BruggerW, Cappuzzo F, Ciuleanu T,Mok T, Reck M, Tan EH, Delmar P, Klingelschmitt G, Yin AY, Spleiss O,Wu L, Shames DS, 2016, Examining treatment outcomeswith Erlotinib in patients with advanced non-small cell lung cancer whose tumors harbor uncommon EGFR mutations. J Thorac Oncol 11(4):545– 555
Shajani-Yi Z, de Abreu FB, Peterson JD, Tsongalis GJ, 2018, Frequency of somatic TP53 mutations in combination with known pathogenicmutations in colon adenocarcinoma, non-small cell lung carcinoma, and gliomas as identified by next-generation sequencing. Neoplasia 20(3):256–262
Marte B, 2013, Tumour heterogeneity. Nature 501:327
Bhattacharya S, SocinskiMA, Burns TF, 2015, KRAS mutant lung cancer: progress thus far on an elusive therapeutic target. Clin Transl Med 4(1):35
Del Re M, Rofi E, Restante G, Crucitta S, Arrigoni E, Fogli S et al, 2017, Implications of KRAS mutations in acquired resistance to treatment in NSCLC. Oncotarget 9(5):6630–6643
Ding L, Getz G,Wheeler DA, Mardis ER,McLellanMD, Cibulskis K et al, 2008, Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455(7216):1069–1075
Pecuchet N, Laurent-Puig P, Mansuet-Lupo A, Legras A, Alifano M, Pallier K et al, 2017, Different prognostic impact of STK11 mutations in non-squamous non-small-cell lung cancer. Oncotarget 8(14):23831–23840
Shinozaki E, Yoshino T, Yamazaki K, Muro K, Yamaguchi K, Nishina T et al, 2017, Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics, BREAC, study. Br J Cancer 117(10):1450–1458
Carter J, Tseng L-H, Zheng G, Dudley J, Illei P, Gocke CD, Eshleman JR, Lin MT, 2015, Non-p.V600E BRAF mutations are common using amore sensitive and broad detection tool.AmJ Clin Pathol 144(4):620–628
Heidorn SJ, Milagre C,Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, Hussain J, Reis-Filho JS, Springer CJ, Pritchard C, Marais R, 2010, Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140(2):209–221
Cancer Genome Atlas Research Network, 2014, Comprehensive molecular profiling of lung adenocarcinoma. Nature 511(7511): 543–550
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2795
EP 2800
DI 10.1007/s12253-019-00713-1
PG 6
ER
PT J
AU Burian, A
Lujber, L
Gerlinger, I
Jarai, T
Orosz,
Turiak, L
Acs, A
Hegedus, Z
Konigne Peter, A
Tornoczki, T
Gombos, K
Mark, L
AF Burian, Andras
Lujber, Laszlo
Gerlinger, Imre
Jarai, Tamas
Orosz, Eva
Turiak, Lilla
Acs, Andras
Hegedus, Zoltan
Konigne Peter, Aniko
Tornoczki, Tamas
Gombos, Katalin
Mark, Laszlo
TI Label-Free Semiquantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics Analysis of Laryngeal/Hypopharyngeal Squamous Cell Carcinoma on Formalin-Fixed, Paraffin-Embedded Tissue Samples - a Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Biomarker discovery; Laryngeal cancer; LC/MS; Squamous cell carcinoma; Proteomics
ID Biomarker discovery; Laryngeal cancer; LC/MS; Squamous cell carcinoma; Proteomics
AB Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aimof this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.
C1 [Burian, Andras] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti Klinika, Munkacsy M Str 2, H-7621 Pecs, Hungary.
[Lujber, Laszlo] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti Klinika, Munkacsy M Str 2, H-7621 Pecs, Hungary.
[Gerlinger, Imre] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti Klinika, Munkacsy M Str 2, H-7621 Pecs, Hungary.
[Jarai, Tamas] Tolna County Balassa Janos Hospital, Beri Balogh Adam Str 5-7, H-7100 Szekszard, Hungary.
[Orosz, Eva] PTE KK, Ful-Orr-Gegeszeti es Fej-Nyaksebeszeti Klinika, Munkacsy M Str 2, H-7621 Pecs, Hungary.
[Turiak, Lilla] Hungarian Academy of Sciences, Research Centre for Natural Sciences, MS Proteomics Research Group, Magyar tudosok Blvd 2, H-1117 Budapest, Hungary.
[Acs, Andras] Hungarian Academy of Sciences, Research Centre for Natural Sciences, MS Proteomics Research Group, Magyar tudosok Blvd 2, H-1117 Budapest, Hungary.
[Hegedus, Zoltan] Hungarian Academy of Sciences, Biological Research Centre, Institute of Biophysics, Temesvari Blvd 62, H-6726 Szeged, Hungary.
[Konigne Peter, Aniko] PTE KK, Bioanalitikai Intezet, Honved Str 1, H-7624 Pecs, Hungary.
[Tornoczki, Tamas] University of Pecs, Department of Pathology, Szigeti Str 12, H-7624 Pecs, Hungary.
[Gombos, Katalin] University of Pecs, Department of Laboratory Medicine, Ifjusag Str 13, H-7624 Pecs, Hungary.
[Mark, Laszlo] University of Pecs, Institute of Biochemistry and Medical Chemistry, Szigeti Str 12, H-7624 Pecs, Hungary.
RP Mark, L (reprint author), University of Pecs, Institute of Biochemistry and Medical Chemistry, H-7624 Pecs, Hungary.
EM laszlo.mark@aok.pte.hu
CR Marur S, Forastiere AA, 2008, Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc 83:489– 501
Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wunsch-Filho V, Franceschi S, Hayes RB, Herrero R, Kelsey K, Koifman S, la Vecchia C, Lazarus P, Levi F, Lence JJ, Mates D,Matos E, Menezes A,McCleanMD,Muscat J, Eluf-Neto J, Olshan AF, PurdueM, Rudnai P, Schwartz SM, Smith E, Sturgis EM, Szeszenia-Dabrowska N, Talamini R, Wei Q, Winn DM, Shangina O, Pilarska A, Zhang ZF, Ferro G, Berthiller J, Boffetta P, 2009, Interaction between tobacco and alcohol use and the risk of head and neck Cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomark Prev 18:541–550
Argiris A, Karamouzis MV, Raben D, Ferris RL, 2008, Head and neck cancer. Lancet 371:1695–1709
Erich K, Reinle K, Muller T, Munteanu B, Sammour DA, Hinsenkamp I, Gutting T, Burgermeister E, Findeisen P, Ebert MP, Krijgsveld J, Hopf C, 2019, Spatial distribution of endogenous tissue protease activity in gastric carcinoma mapped by MALDI mass spectrometry imaging. Mol Cell Proteomics 18: 151–161
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Paulo JA, Lee LS, Banks PA, Steen H, Conwell DL, 2012, Proteomic analysis of formalin-fixed paraffin-embedded pancreatic tissue using liquid chromatography tandem mass spectrometry. Pancreas 41:175–185
Carnielli CM, Macedo CCS, De Rossi T, Granato DC, Rivera C, Domingues RR et al, 2018, Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. Nat Commun 9:3598
Li L, Zhang Z,Wang C, Miao L, Zhang J, Wang J, Jiao B, Zhao S, 2014, Quantitative proteomics approach to screening of potential diagnostic and therapeutic targets for laryngeal carcinoma. PLoS One 9:e90181
Metz B, Kersten GF, Hoogerhout P, Brugghe HF, Timmermans HA, de Jong A et al, 2004, Identification of formaldehydeinduced modifications in proteins: reactions with model peptides. J Biol Chem 279:6235–6243
Fowler CB, O'Leary TJ, Mason JT et al, 2013, Toward improving the proteomic analysis of formalin-fixed, paraffin-embedded tissue. Expert Rev Proteomics 10:389–400
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2801
EP 2807
DI 10.1007/s12253-020-00849-5
PG 7
ER
PT J
AU Son, JH
Mo, YH
Choi, JE
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Mo, Yoon Ha
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Promoter Mutation Analysis of Long-Non-coding RNA RMRP Gene in Solid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Mo, Yoon Ha] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G, 2017, Recurrent and functional regulatory mutations in breast cancer. Nature 547:55–60
Huarte M, 2015, The emerging role of lncRNAs in cancer. Nat Med 21:1253–1261
Hermanns P, Bertuch AA, Bertin TK, Dawson B, Schmitt ME, Shaw C, Zabel B, Lee B, 2005, Consequences of mutations in the noncoding RMRP RNA in cartilage-hair hypoplasia. Hum Mol Genet 14:3723–3740
Xiao X, Gu Y,Wang G, Chen S, 2019, c-Myc, RMRP, andmiR-34a- 5p form a positive-feedback loop to regulate cell proliferation and apoptosis in multiple myeloma. Int J Biol Macromol 122:526–537
Shao Y, Ye M, Li Q, SunW, Ye G, Zhang X, Yang Y, Xiao B, Guo J, 2016, LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. Oncotarget 7:37812–37824
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH, 2012, Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 60:943–952
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2809
EP 2810
DI 10.1007/s12253-019-00723-z
PG 2
ER
PT J
AU Son, JH
Choi, JE
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Intratumoral heterogeneity of FLCN somatic mutations in gastric and colorectal cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Hartman TR, Nicolas E, Klein-Szanto A, Al-Saleem T, Cash TP, Simon MC, Henske EP, 2009, The role of the Birt-Hogg-Dube protein in mTOR activation and renal tumorigenesis. Oncogene 28: 1594–1604
Khoo SK, Giraud S, Kahnoski K, Chen J, Motorna O, Nickolov R, Binet O, Lambert D, Friedel J, Levy R, Ferlicot S, Wolkenstein P, Hammel P, Bergerheim U, Hedblad MA, Bradley M, Teh BT, Nordenskjold M, Richard S, 2002, Clinical and genetic studies of Birt-Hogg-Dube syndrome. J Med Genet 39:906–912
Kahnoski K, Khoo SK, Nassif NT, Chen J, Lobo GP, Segelov E, Teh BT, 2003, Alterations of the Birt-Hogg-Dube gene, BHD, in sporadic colorectal tumours. J Med Genet 40:511–515
Shin JH, Shin YK, Ku JL, Jeong SY, Hong SH, Park SY, Kim WH, Park JG, 2003, Mutations of the Birt-Hogg-Dube, BHD, gene in sporadic colorectal carcinomas and colorectal carcinoma cell lines with microsatellite instability. J Med Genet 40:364–367
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Choi EJ, Kim MS, Song SY, Yoo NJ, Lee SH, 2017, Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability. Pathol Oncol Res 23:145–149
McGranahan N, Swanton C, 2015, Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27: 15–26
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2811
EP 2812
DI 10.1007/s12253-019-00774-2
PG 2
ER
PT J
AU Son, JH
Choi, JE
Yoo, JN
Lee, HS
AF Son, Ji Hyun
Choi, Ji Eun
Yoo, Jin Nam
Lee, Hyung Sug
TI Somatic Mutations and Intratumoral Heterogeneity of Cancer-Related Genes NLK, YY1 and PA2G4 in Gastric and Colorectal Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE NLK; YY1; PG2G4; Mutation; Cancer; Microsatellite instability
ID NLK; YY1; PG2G4; Mutation; Cancer; Microsatellite instability
AB Many genes act as both tumor suppressor gene (TSG) and proto-oncogene depending on cellular context and cancer type. Nemo-like kinase (NLK) encoding a serine/threonine kinase, Yin Yang 1 (YY1) encoding a zinc-finger transcription factor and PA2G4 encoding an ErbB3 binding protein have both of these two opposing functions. In the present study, we analyzed NLK, YY1 and PA2G4 frameshift mutations in sporadic GC and CRC with high microsatellite instability (MSI-H). Also, regional intratumoral heterogeneity (ITH) of frameshift mutations of these genes was analyzed in CRCs. We found frameshift mutations of NLK, YY1 and PA2G4 in CRC and GC with MSI-H (17/132: 12.9%), but not in those with MSS (0/90). Two (12.5%), one (6.3%) and one (6.3%) CRC (s) of the 16 CRCs exhibited ITH of NLK, YY1 and PA2G4 mutations among the 4–7 regions, suggesting that ITH of the frameshift mutations might be frequent in the CRCs. These results suggest that frameshift mutations of NLK, YY1 and PA2G4 along with the ITH might contribute to MSI-H cancer pathogenesis.
C1 [Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Choi, Ji Eun] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of Pathology, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, 137-701 Seoul, South Korea.
EM suhulee@catholic.ac.kr
CR Shen L, Shi Q, Wang W, 2018, Double agents: genes with both oncogenic and tumor-suppressor functions. Oncogenesis 7:25
Eskelinen EL, 2011, The dual role of autophagy in cancer. Curr Opin Pharmacol 11:294–300
Li SZ, Zeng F, Li J, Shu QP, Zhang HH, Xu J, Ren JW, Zhang XD, SongXM, Du RL, 2018, Nemo-like kinase, NLK, primes colorectal cancer progression by releasing the E2F1 complex from HDAC1. Cancer Lett 431:43–53
Hays E, Bonavida B, 2019, YY1 regulates cancer cell immune resistance by modulating PD-L1 expression. Drug Resist Updat 43: 10–28
Nguyen DQ, Hoang DH, Nguyen Vo TT, Huynh V, Ghoda L, Marcucci G, Nguyen LXT, 2018, The role of ErbB3 binding protein 1 in cancer: friend or foe? J Cell Physiol 233:9110–9120
Imai K, Yamamoto H, 2008, Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Choi EJ, Kim MS, Song SY, Yoo NJ, Lee SH, 2017, Intratumoral heterogeneity of Frameshift mutations in MECOM gene is frequent in colorectal cancers with high microsatellite instability. Pathol Oncol Res 23:145–149
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2813
EP 2815
DI 10.1007/s12253-019-00785-z
PG 3
ER
PT J
AU Harsha, SB
Manikandan, R
Sreerag, S
Dorairajan, NL
Rajesh, GN
Kar, R
AF Harsha, Sri Bokka
Manikandan, Ramanitharan
Sreerag, K. Sreenivasan
Dorairajan, Narayanan Lalgudi
Rajesh, Ganesh Nachiappa
Kar, Rakhi
TI Eosinophilic Leukemoid Reaction with Eosinophilic Tumor Tissue Infiltration as an Extermely Poor Prognostic Factor in Urinary Bladder Cancer- a Known Entity Revisited
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Bladder cancer; Leukemoid reaction; Eosinophilia; Hematuria
ID Bladder cancer; Leukemoid reaction; Eosinophilia; Hematuria
AB Eosinophilia can be a manifestation of a variety of causes such as infections, allergic reactions and autoimmune processes. Also, it is described in various solid malignancies in the presence of tumour eosinophilic infiltration. We report a patient of high-grade urinary bladder cancer with eosinophilic leukemoid reaction and tumour histopathology demonstrated diffuse infiltration of eosinophils. Though the entity is described to carry a good prognosis in literature, our experience is totally different as the patient deteriorated rapidly in a matter of days, was deemed inoperable in view of worsening performance status and was referred for palliative management.
C1 [Harsha, Sri Bokka] JIPMER, Department of Urology and Renal TransplantationPuducherry, India.
[Manikandan, Ramanitharan] JIPMER, Department of Urology and Renal TransplantationPuducherry, India.
[Sreerag, K. Sreenivasan] JIPMER, Department of Urology and Renal TransplantationPuducherry, India.
[Dorairajan, Narayanan Lalgudi] JIPMER, Department of Urology and Renal TransplantationPuducherry, India.
[Rajesh, Ganesh Nachiappa] JIPMER, Department of PathologyPuducherry, India.
[Kar, Rakhi] JIPMER, Department of PathologyPuducherry, India.
RP Harsha, SB (reprint author), JIPMER, Department of Urology and Renal Transplantation, Puducherry, India.
EM bokkaharsha7@gmail.com
CR Lowe D, Jorizzo J, Hutt MS, 1981 Dec, Tumour-associated eosinophilia: a review. J Clin Pathol 34(12):1343–1348
Flamm J, 1992 Aug, Tumor-associated tissue inflammatory reaction and eosinophilia in primary superficial bladder cancer. Urology. 40(2):180–185
Lowe D, Fletcher CD, Gower RL, 1984 May, Tumour-associated eosinophilia in the bladder. J Clin Pathol 37(5):500–502
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2817
EP 2819
DI 10.1007/s12253-020-00807-1
PG 3
ER
PT J
AU Bareeqa, BS
Ahmed, IS
Samar, SS
Humayun, HS
AF Bareeqa, Beenish Syeda
Ahmed, Ijlal Syed
Samar, Sana Syeda
Humayun, Hasham Syed
TI A Letter to Editor Regarding the Article “Identification of Differentially Expressed Proteins from Smokeless Tobacco Addicted Patients Suffering from Oral Squamous Cell Carcinoma”
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Bareeqa, Beenish Syeda] Jinnah Medical and Dental College, 22-23 Shaheed-e-Millat RoadKarachi, Pakistan.
[Ahmed, Ijlal Syed] Liaquat National Medical College and HospitalKarachi, Pakistan.
[Samar, Sana Syeda] Jinnah Sindh Medical UniversityKarachi, Pakistan.
[Humayun, Hasham Syed] Jinnah Medical and Dental CollegeKarachi, Pakistan.
RP Bareeqa, BS (reprint author), Jinnah Medical and Dental College, Karachi, Pakistan.
EM syedabeenishbareeqa@gmail.com
CR Malik, U. U., Siddiqui, I. A., Ilyas, A., Hashim, Z., Staunton, L., Kwasnik, A., . . . Zarina, S., 2019). Identification of differentially expressed proteins from smokeless tobacco addicted patients suffering from Oral squamous cell carcinoma. Pathol Oncol Res, 1–9
Rivera C, 2015, Essentials of oral cancer. Int J Clin Exp Pathol 8(9): 11884–11894
Ebbert JO, Patten CA, Schroeder DR, 2006, The Fagerstrom test for nicotine dependence-smokeless tobacco, FTND-ST). Addict Behav 31(9):1716–1721
Mushtaq N, Huque R, Beebe LA, Shah S, Siddiqi K, 2019, Evaluation of tobacco dependence measures in south Asian smokeless tobacco users. Drug Alcohol Depend 203:66–71
Hoppin JA, Tolbert PE, Taylor JA, Schroeder JC, Holly EA, 2002, Potential for selection bias with tumor tissue retrieval in molecular epidemiology studies. Ann Epidemiol 12(1):1–6
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2821
EP 2822
DI 10.1007/s12253-020-00812-4
PG 2
ER
PT J
AU Tsiambas, E
Papanikolaou, V
Chrysovergis, A
Mastronikolis, N
Ragos, V
Kavantzas, N
Lazaris, A
Kyrodimos, E
AF Tsiambas, Evangelos
Papanikolaou, Vasileios
Chrysovergis, Aristeidis
Mastronikolis, Nicholas
Ragos, Vasileios
Kavantzas, Nikolaos
Lazaris, C. Andreas
Kyrodimos, Efthymios
TI Coronavirus in Hematologic Malignancies: Targeting Molecules Beyond the Angiotensin-Converting Enzyme 2 (ACE2) Wall in COVID-19
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Tsiambas, Evangelos] 401 General Army Hospital, Department of Pathology-CytologyAthens, Greece.
[Papanikolaou, Vasileios] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
[Chrysovergis, Aristeidis] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
[Mastronikolis, Nicholas] University of Patras, Medical School, Department of Otorhinolaryngology, Head and Neck SurgeryPatras, Greece.
[Ragos, Vasileios] University of Ioannina, School of Health Sciences, Department of Maxillofacial and Department of MedicineIoannina, Greece.
[Kavantzas, Nikolaos] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of Pathology, 17 Patriarchou Grigoriou E Street, Ag. Paraskevi, 153 41 Athens, Greece.
[Lazaris, C. Andreas] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of Pathology, 17 Patriarchou Grigoriou E Street, Ag. Paraskevi, 153 41 Athens, Greece.
[Kyrodimos, Efthymios] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
RP Tsiambas, E (reprint author), 401 General Army Hospital, Department of Pathology-Cytology, Athens, Greece.
EM tsiambasecyto@yahoo.gr
CR Fehr AR, Perlman S, 2015, Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 1282:1–23
Wu A, Peng Y, Huang B et al, 2020, Genome Composition and Divergence of the Novel Coronavirus, 2019-nCoV, Originating in China. Cell Host Microb 27(3):325–328
Li F, 2016, Structure, function, and evolution of coronavirus spike proteins. Ann Rev Virol 3:237–261
Song Z, Xu Y, Bao L et al, 2019, From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 11:E59–E63
Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, Mazet JK, Hu B, ZhangW, Peng C, Zhang YJ, Luo CM, Tan B,Wang N, Zhu Y, Crameri G, Zhang SY, Wang LF, Daszak P, Shi ZL, 2013, Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 503:535–538
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D, 2020, Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 180:1–12
Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E, 2020, The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoVof the same clade. Antiviral Res 176:104742–247
Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W(1992, Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp 160. Nature 360(6402):358–361
Ogimi C, Waghmare AA, Kuypers JM et al, 2017, Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies 64(11):1532–1539
Hakki M, Rattray RM, Press RD, 2015, The clinical impact of coronavirus infection in patients with hematologic malignancies and hematopoietic stem cell transplant recipients. J Clin Virol 68:1–5
Joshi S, Wollenzien H, Leclerc E, Jarajapu YP, 2019, Hypoxic regulation of angiotensin- converting enzyme 2 and Mas receptor in human CD34+ cells. J Cell Physiol 234(11):20420– 20431
Hu W, Yen YT, Singh S, Kao CL, Wu-Hsieh BA, 2012, SARSCoV regulates immune function-related gene expression in human monocytic cells. Viral Immunol 25(4):277–288
Fu J, Zhang J, Gong Y, Testa CL, Klein-Szanto AJ, 2015, Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells. Mol Carcino 54(9):698–706
Braun E, Hotter D, Koepke L et al, 2019, Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. Cell Rep 27(7):2092–2104
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2823
EP 2825
DI 10.1007/s12253-020-00810-6
PG 3
ER
PT J
AU Yoo, HK
Choi, T
Lee, HL
Song, JM
Chung, IB
AF Yoo, Han Koo
Choi, Taesoo
Lee, Hyung-Lae
Song, Jeong Min
Chung, I Benjamin
TI Aggressive Paraganglioma of the Urinary Bladder with Local Recurrence and Pelvic Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Paraganglioma; Urinary bladder; Neoplasm metastasis
ID Paraganglioma; Urinary bladder; Neoplasm metastasis
AB Many pheochromocytoma and extra-adrenal paraganglioma are benign, but some are malignant. Pheochromocytoma of the Adrenal gland Scaled Score analyzed the histological characteristics of the tumor. Tumors with a Pheochromocytoma of the Adrenal gland Scaled Score of 4 or higher have a higher risk of recurrence. This pattern is thought to be applicable to paraganglioma as well, and to future patient follow-up efforts. We report a recurrent and metastatic paraganglioma of the urinary bladder.
C1 [Yoo, Han Koo] Stanford University Medical Center, Department of UrologyStanford, CA, USA.
[Choi, Taesoo] Kyung Hee University, School of Medicine, Department of Urology, 892, Dongnam-ro, Gangdong-gu, 05278 Seoul, South Korea.
[Lee, Hyung-Lae] Kyung Hee University, School of Medicine, Department of Urology, 892, Dongnam-ro, Gangdong-gu, 05278 Seoul, South Korea.
[Song, Jeong Min] Kyung Hee University, College of Medicine, Department of Pathology, 892, Dongnam-ro, Gangdong-gu, 05278 Seoul, South Korea.
[Chung, I Benjamin] Stanford University Medical Center, Department of UrologyStanford, CA, USA.
RP Yoo, HK (reprint author), Stanford University Medical Center, Department of Urology, Stanford, USA.
EM yookoohan@khu.ac.kr
CR Pacak K, Wimalawansa SJ, 2015, Pheochromocytoma and paraganglioma. Endocr Pract: Off J Am Coll Endocrinol Am Assoc Clin Endocrinologists 21(4):406–412. , DOI 10. 4158/EP14481.RA
Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G, 2002, Biochemical diagnosis of pheochromocytoma: which test is best? Jama 287(11):1427–1434. , DOI 10.1001/jama.287.11. 1427
Walz MK, Alesina PF, Wenger FA, Deligiannis A, Szuczik E, Petersenn S, Ommer A, Groeben H, Peitgen K, Janssen OE, Philipp T, Neumann HP, Schmid KW, Mann K, 2006, Posterior retroperitoneoscopic adrenalectomy–results of 560 procedures in 520 patients. Surgery 140(6):943–948; discussion 948-950. https:// doi.org/10.1016/j.surg.2006.07.039
Gonias S, Goldsby R, Matthay KK, Hawkins R, Price D, Huberty J, Damon L, Linker C, Sznewajs A, Shiboski S, Fitzgerald P, 2009, Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol: Off J Am Soc Clin Oncol 27(25):4162–4168. https:// doi.org/10.1200/JCO.2008.21.3496
Thompson LD, 2002, Pheochromocytoma of the adrenal gland scaled score, PASS, to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. AmJ Surg Pathol 26(5):551–566. , DOI 10.1097/00000478- 200205000-00002
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2827
EP 2829
DI 10.1007/s12253-020-00841-z
PG 3
ER
PT J
AU Hatzl, S
Posch, F
Schulz, E
Gornicec, M
Deutsch, A
Beham-Schmid, Ch
Pichler, M
Greinix, H
Sill, H
Zebisch, A
Neumeister, P
Prochazka, K
AF Hatzl, Stefan
Posch, Florian
Schulz, Eduard
Gornicec, Maximilian
Deutsch, Alexander
Beham-Schmid, Christine
Pichler, Martin
Greinix, Hildegard
Sill, Heinz
Zebisch, Armin
Neumeister, Peter
Prochazka, T. Katharina
TI The Role of Immunohistochemical Overexpression of p53 as Adverse Prognostic Factor in Primary Testicular Diffuse Large B Cell Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Hatzl, Stefan] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Posch, Florian] Medical University of Graz, Department of Internal Medicine, Division of OncologyGraz, Austria.
[Schulz, Eduard] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Gornicec, Maximilian] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Deutsch, Alexander] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Beham-Schmid, Christine] Medical University of Graz, Department of PathologyGraz, Austria.
[Pichler, Martin] Medical University of Graz, Department of Internal Medicine, Division of OncologyGraz, Austria.
[Greinix, Hildegard] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Sill, Heinz] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Zebisch, Armin] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Neumeister, Peter] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
[Prochazka, T. Katharina] Medical University of Graz, Department of Internal Medicine, Division of Hematology, Auenbruggerplatz 38D, A-8036 Graz, Austria.
RP Hatzl, S (reprint author), Medical University of Graz, Department of Internal Medicine, Division of Hematology, A-8036 Graz, Austria.
EM stefan.hatzl@medunigraz.at
CR Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ, 2020, Diffuse large B-cell lymphoma variants: an update. Pathology. 52:53–67
Magnoli F, Bernasconi B,Vivian L, Proserpio I, Pinotti G, Campiotti L, Mazzucchelli L, Sessa F, Tibiletti MG, Uccella S, 2018, Primary extranodal diffuse large B-cell lymphomas: many sites, many entities? Clinico-pathological, immunohistochemical and cytogenetic study of 106 cases. Cancer Genet 228-229:28–40
Peroja P, Pedersen M, Mantere T, Norgaard P, Peltonen J, Haapasaari KM, Bohm J, Jantunen E, Turpeenniemi-Hujanen T, Rapakko K, Karihtala P, Soini Y, Vasala K, Kuittinen O, 2018, Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP. Sci. Rep. 8:14814. , DOI 10.1038/ s41598-018-33230-3
Hatzl S, Posch F, Deutsch A, Beham-Schmid C, Stoger H, Greinix H, Pichler M, Neumeister P, Prochazka KT, 2020, Immunohistochemistry for c-myc and bcl-2 overexpression improves risk stratification in primary central nervous system lymphoma. Hematol Oncol
Wang XJ, Jeffrey ML, Bueso-Ramos CE, Tang G, Wang S, Oki Y, Desai P, Khoury JD, Miranda RN, Tang Z, Reddy N, Li S, 2017, P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma. Mod Pathol 30:194–203
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2831
EP 2833
DI 10.1007/s12253-020-00864-6
PG 3
ER
PT J
AU Zhou, Sh
Zhang, D
Li, J
Zhao, J
Wang, G
Zhang, Y
Bai, Y
Chen, D
Wu, H
AF Zhou, Shaoqiang
Zhang, Ding
Li, Junjie
Zhao, Jing
Wang, Guoqiang
Zhang, Yuzi
Bai, Yuezong
Chen, Dedian
Wu, Hao
TI Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE Carcinoma; Genetics; RAS gene; Next-generation sequencing
ID Carcinoma; Genetics; RAS gene; Next-generation sequencing
AB RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker. It would also be a promising drug target. Several trials which evaluating the efficacy of RAS G12C inhibitor in solid tumors are initiated. Herein, we analyzed the alterations status of KRAS/NRAS/HRAS across diverse solid tumors. The sing nucleotide variants (SNV) and copy number variants (CNV) data of 17993 Chinese patients from 22 types of cancer were obtained in our database. Genomic profiling of DNA was performed through a next-generation sequencing on tissue. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis. Among 17993 pancancer patients, the total RAS variants frequency was 22.58%. KRAS was the most frequently altered, followed by NRAS and HRAS. For the SNV, KRAS were most commonly found in pancreas cancer, intestine cancer and colorectal cancer. Further analysis among KRAS SNV patients showed that the mutation frequency of KRAS G12C, G12D, G12R, and G12V was 1.81%, 6.81%, 0.69% and 4.25%, respectively. A total of 21 in 22 types of solid tumors had KRAS G12C/D/R/V pathogenic or likely pathogenic mutation, which occurred most frequently in colorectal cancer, pancreas cancer and lung cancer. Our results suggested that a variety of solid tumors may harbor KRAS G12C/D/R/V mutation. These patients may benefit from KRAS inhibitors.
C1 [Zhou, Shaoqiang] The Third Affiliated Hospital ofKunming Medical University (Yunnan Tumor Hospital), Galactophore Department, No.518 Kunzhou Road, 650118 Kunming, Yunnan Province, China.
[Zhang, Ding] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Li, Junjie] The Central Hospital of Zibo, Department of AnesthesiologyZibo, China.
[Zhao, Jing] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Wang, Guoqiang] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhang, Yuzi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Bai, Yuezong] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Chen, Dedian] The Third Affiliated Hospital ofKunming Medical University (Yunnan Tumor Hospital), Galactophore Department, No.518 Kunzhou Road, 650118 Kunming, Yunnan Province, China.
[Wu, Hao] Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, NO.300 Guangzhou Road, 210029 Nanjing, Jiangsu Province, China.
RP Wu, H (reprint author), Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, 210029 Nanjing, China.
EM whdactor@163.com
CR Vetter IR, Wittinghofer A, 2001, The guanine nucleotide-binding switch in three dimensions. Science 294(5545):1299–1304
Wan XB,Wang AQ, Cao J et al, 2019, Relationships among KRAS mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer. World J Gastroenterol 25(7):808–823
Lartigue JD, 2019, New strategies generate optimism for targeting “Undruggable” KRAS. Oncol Live 20:19
Chaft JE, Litvak A, Arcila ME et al, 2014, Phase II study of the GI- 4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation. Clin Lung Cancer 15(6):405–410
Shepherd FA, Domerg C, Hainaut P et al, 2013, Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 31(17): 2173–2181
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2835
EP 2837
DI 10.1007/s12253-020-00845-9
PG 3
ER
PT J
AU Tsiambas, E
Chrysovergis, A
Papanikolaou, V
Mastronikolis, N
Ragos, V
Kavantzas, N
Lazaris, A
Patsouris, E
Riziotis, Ch
Paschopoulos, M
Kyrodimos, E
AF Tsiambas, Evangelos
Chrysovergis, Aristeidis
Papanikolaou, Vasileios
Mastronikolis, Nicholas
Ragos, Vasileios
Kavantzas, Nikolaos
Lazaris, C. Andreas
Patsouris, Efstratios
Riziotis, Christos
Paschopoulos, Minas
Kyrodimos, Efthymios
TI Chromosome X riddle in SARS-CoV-2 (COVID-19) - related lung pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
C1 [Tsiambas, Evangelos] VA Hospital (NIMTS), Department of CytologyAthens, Greece.
[Chrysovergis, Aristeidis] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
[Papanikolaou, Vasileios] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
[Mastronikolis, Nicholas] University of Patras, Medical School, Department of Otorhinolaryngology, Head and Neck SurgeryPatras, Greece.
[Ragos, Vasileios] University of Ioannina, School of Health Sciences, Department of Maxillofacial and Department of MedicineIoannina, Greece.
[Kavantzas, Nikolaos] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Lazaris, C. Andreas] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Patsouris, Efstratios] National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, First Department of PathologyAthens, Greece.
[Riziotis, Christos] National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute, Photonics for Nanoapplications LaboratoryAthens, Greece.
[Paschopoulos, Minas] Ioannina University Hospital, Department of Obstetrics and GynecologyIoannina, Greece.
[Kyrodimos, Efthymios] National and Kapodistrian, University of Athens, Hippocration Hospital, 1st ENT DepartmentAthens, Greece.
RP Tsiambas, E (reprint author), VA Hospital (NIMTS), Department of Cytology, Athens, Greece.
EM tsiambasecyto@yahoo.gr
CR Wu A, Peng Y, Huang B et al, 2020, Genome Composition and Divergence of the Novel Coronavirus, 2019-nCoV, Originating in China. Cell Host Microb 27(3):325–328
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2020
VL 26
IS 4
BP 2839
EP 2841
DI 10.1007/s12253-020-00878-0
PG 3
ER
PT J
AU Shen, H
Liao, K
Wu, W
Li, G
Chen, Sh
Nan, N
Yu, H
Wu, H
AF Shen, Hua
Liao, Kai
Wu, Weili
Li, Gongyu
Chen, Shijin
Nan, Nan
Yu, Hongbo
Wu, Hongfei
TI Case Report: Mucinous Adenocarcinoma Arising From Congenital Ejaculatory Duct Cyst
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE mucinous adenocarcinoma; ejaculatory duct; ejaculatory duct cyst; ejaculatory duct tumor; ejaculatory duct adenocarcinoma
ID mucinous adenocarcinoma; ejaculatory duct; ejaculatory duct cyst; ejaculatory duct tumor; ejaculatory duct adenocarcinoma
AB Herein we present a previously unreported rare case of mucinous adenocarcinoma arising from a congenital ejaculatory duct cyst. Radiographic and endoscopic examinations revealed the tumor occurred in a cyst running through the prostate. Initially, the immunohistochemical pathology results showed that it was a metastatic mucinous adenocarcinoma, but no other primary lesions were clinically evidenced. Based on the embryonic development process of the male urogenital tract, the malformation of the patient’s ejaculatory duct, and the pathological examination of the resected specimen, we considered the tumor to be a primary mucinous adenocarcinoma which originating from the hypoplastic ejaculatory duct. The tumor may have developed from the foci of intestinal metaplasia from cloacal remnants during embryonic development.
C1 [Shen, Hua] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
[Liao, Kai] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
[Wu, Weili] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
[Li, Gongyu] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
[Chen, Shijin] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of PathologyNanjing, China.
[Nan, Nan] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of RadiologyNanjing, China.
[Yu, Hongbo] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
[Wu, Hongfei] The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of UrologyNanjing, China.
RP Shen, H (reprint author), The Affiliated BenQ Hospital of Nanjing Medical University, BenQ Medical Center, Department of Urology, Nanjing, China.
EM shnjmu@hotmail.com
CR Bohman, K. D., and Osunkoya, A. O., 2012). Mucin-producing tumors and tumor-like lesions involving the prostate: a comprehensive review. Adv. Anat. Pathol. 19, 6), 374–387., DOI 10.1097/PAP.0b013e318271a361
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 528050
EP 528054
DI 10.3389/pore.2021.528050
PG 5
ER
PT J
AU Bi, Y
Zhang, J
Zeng, D
Chen, L
Ye, W
Yang, Q
Ling, Y
AF Bi, Yanzhi
Zhang, Junling
Zeng, Dongxiang
Chen, Lili
Ye, Wei
Yang, Quanliang
Ling, Yang
TI Cholinesterase is Associated With Prognosis and Response to Chemotherapy in Advanced Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cholinesterase; prognosis; gastric cancer; chemotherapy; progression-free survival; overall survival
ID cholinesterase; prognosis; gastric cancer; chemotherapy; progression-free survival; overall survival
AB Background: Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Methods: Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). Results: A total of 150 advanced GC patients were included and divided into serum level ≥5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141–2.243; p=0.006), poorer OS (HR, 1.76; 95% CI, 1.228–2.515; p=0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272–1.129; p=0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response (p < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28–2.57; p=0.0002). The medium OS was 13.1 months in patients with increased posttreatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29–2.71; p=0.0002). Conclusion: Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC.
C1 [Bi, Yanzhi] Changzhou Tumor Hospital Affiliated to Soochow University, Department of OncologyChangzhou, China.
[Zhang, Junling] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zeng, Dongxiang] Changzhou Tumor Hospital Affiliated to Soochow University, Department of OncologyChangzhou, China.
[Chen, Lili] The Suqian Affiliated Hospital of Xuzhou Medicine University, Department of HematologySuqian, China.
[Ye, Wei] Changzhou Tumor Hospital Affiliated to Soochow University, Department of OncologyChangzhou, China.
[Yang, Quanliang] Changzhou Tumor Hospital Affiliated to Soochow University, Department of OncologyChangzhou, China.
[Ling, Yang] Changzhou Tumor Hospital Affiliated to Soochow University, Department of OncologyChangzhou, China.
RP Ling, Y (reprint author), Changzhou Tumor Hospital Affiliated to Soochow University, Department of Oncology, Changzhou, China.
EM medilyn@vip.126.com
CR Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A Global cancer statistics,, 2012). CA Cancer J Clin, 2015, 65:87–108., DOI 10.3322/ caac.21262
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Gu S-Z, Zhao XH, Quan P, Li SB, Pan BR Alterations of serum cholinesterase in patients with gastric cancer. Wjg, 2005, 11:4604–6., DOI 10.3748/wjg.v11.i29.4604
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 580800
EP 580807
DI 10.3389/pore.2021.580800
PG 8
ER
PT J
AU Kiss, T
Jambor, K
Koroknai, V
Szasz, I
Bardos, H
Mokanszki, A
Adany, R
Balazs, M
AF Kiss, Timea
Jambor, Krisztina
Koroknai, Viktoria
Szasz, Istvan
Bardos, Helga
Mokanszki, Attila
Adany, Roza
Balazs, Margit
TI Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE osteopontin expression; osteopontin knockdown; protein expression profile; melanoma progression; invasion; proliferation
ID osteopontin expression; osteopontin knockdown; protein expression profile; melanoma progression; invasion; proliferation
AB Osteopontin (OPN) is a multifunctional phosphoprotein that is expressed in different types of cancers, including melanoma. OPN overexpression is associated with tumor progression and metastasis formation; however, the role of OPN in cell invasion and metastasis formation is not completely understood. In this study we aimed to define OPN expression in melanoma tissues and cell lines and investigate the effect of OPN expression on cell proliferation and invasion after inhibiting OPN expression with small interfering RNA (siRNA). OPN gene expression was determined by qRT-PCR, while protein expression was examined using a Proteome Profiler Oncology Array. siRNA-mediated OPN knockdown led to decreased OPN expression in melanoma cell lines, which was associated with decreased cell proliferation and invasion. Proteome profile analysis revealed significantly different protein expression between the original and transfected cell lines. The altered expression of the differently expressed proteins was validated at the mRNA level. Furthermore, OPN-specific siRNA was able to reduce OPN expression and inhibit the invasiveness of melanoma cells. Our results revealed for the first time that silencing the OPN gene influences proliferation and invasion of melanoma cells by effecting EGFR, tenascin C, survivin, galectin-3 and enolase 2 expression. To predict proteinprotein interactions along with putative pathways we used STRING analysis for the differentially expressed proteins. These proteins formed multiple clusters, including extracellular matrix organization, regulation of angiogenesis, cell death and cell migration, PI3K-Akt, MAPK and focal adhesion signaling pathways. Taken together these data suggest that OPN might be an ideal target for drug development and therapies.
C1 [Kiss, Timea] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Jambor, Krisztina] Debreceni Egyetem, Egeszsegtudomanyok Doktori IskolaDebrecen, Hungary.
[Koroknai, Viktoria] University of Debrecen, MTA-DE Public Health Research GroupDebrecen, Hungary.
[Szasz, Istvan] University of Debrecen, MTA-DE Public Health Research GroupDebrecen, Hungary.
[Bardos, Helga] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Mokanszki, Attila] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Adany, Roza] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Balazs, Margit] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
RP Balazs, M (reprint author), Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai Tanszek, Debrecen, Hungary.
EM balazs.margit@med.unideb.hu
CR Schadendorf, D., van Akkooi, A. C. J., Berking, C., Griewank, K. G., Gutzmer, R., Hauschild, A., et al., 2018). Melanoma. Lancet. 392, 10151), 971–984., DOI 10. 1016/S0140-6736(18)31559-9
Turner,N., Ware,O., and Bosenberg,M., 2018).Genetics ofmetastasis: melanoma and other cancers.Clin. Exp. Metastasis. 35, 5-6), 379–391., DOI 10.1007/s10585-018-9893-y
Ferguson, P.M., Long, G. V., Scolyer, R. A., and Thompson, J. F., 2018). Impact of genomics on the surgical management of melanoma. Br. J. Surg. 105, 2), e31–e47., DOI 10.1002/bjs.10751
Malissen, N., and Grob, J. J., 2018). Metastatic melanoma: recent therapeutic progress and future perspectives. Drugs. 78, 12), 1197–1209., DOI 10.1007/ s40265-018-0945-z
Guarneri,C.,Bevelacqua, V., Polesel, J., Falzone, L.,Cannavo, P. S., Spandidos,D.A., et al., 2017).NFkappaB inhibition is associated withOPN/MMP9 downregulation in cutaneous melanoma. Oncol. Rep. 37, 2), 737–746., DOI 10.3892/or.2017.5362
Wei, R., Wong, J. P. C., and Kwok, H. F., 2017). Osteopontin–a promising biomarker for cancer therapy. J. Canc. 8, 12), 2173–2183., DOI 10.7150/jca.20480
Icer, M. A., and Gezmen-Karadag,M., 2018). The multiple functions and mechanisms of osteopontin. Clin. Biochem. 59, 17–24., DOI 10.1016/j.clinbiochem.2018.07.003
Zhao, H., Chen, Q., Alam, A., Cui, J., Suen, K. C., Soo, A. P., et al., 2018). The role of osteopontin in the progression of solid organ tumour. Cell Death Dis. 9, 3), 356., DOI 10.1038/s41419-018-0391-6
Wai, P. Y., and Kuo, P. C., 2008). Osteopontin: regulation in tumor metastasis. Canc. Metastasis Rev. 27, 1), 103–118., DOI 10.1007/s10555-007-9104-9
Weber, G. F., Lett, G. S., and Haubein, N. C., 2010). Osteopontin is a marker for cancer aggressiveness and patient survival. Br. J. Canc. 103, 6), 861–869., DOI 10.1038/sj.bjc.6605834
Rakosy, Z., Ecsedi, S., Toth, R., Vizkeleti, L., Hernandez-Vargas, H., Lazar, V., et al., 2013). Integrative genomics identifies gene signature associated with melanoma ulceration. PloS One. 8, 1), e54958., DOI 10.1371/journal.pone.0054958
Yin, M., Soikkeli, J., Jahkola, T., Virolainen, S., Saksela, O., and Holtta, E., 2014). Osteopontin promotes the invasive growth of melanoma cells by activating integrin alphavbeta3 and down-regulating tetraspanin CD9. Am. J. Pathol. 184, 3), 842–858., DOI 10.1016/j.ajpath.2013.11.020
Damsky, W. E., Rosenbaum, L. E., and Bosenberg, M., 2010). Decoding melanoma metastasis. Cancers. 3, 1), 126–163., DOI 10.3390/cancers3010126
Valastyan, S., andWeinberg, R. A., 2011). Tumor metastasis: molecular insights and evolving paradigms. Cell. 147, 2), 275–292., DOI 10.1016/j.cell.2011.09.024
Lambert, A. W., Pattabiraman,D. R., and Weinberg, R.A., 2017). Emerging biological principles of metastasis. Cell. 168, 4), 670–691., DOI 10.1016/j.cell.2016.11.037
Ahmed, M., Sottnik, J. L., Dancik, G. M., Sahu, D., Hansel, D. E., Theodorescu, D., et al., 2016). An osteopontin/CD44 Axis in RhoGDI2-mediated metastasis suppression. Canc. Cell. 30, 3), 432–443., DOI 10.1016/j.ccell.2016.08.002
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 581395
EP 581404
DI 10.3389/pore.2021.581395
PG 10
ER
PT J
AU Gao, Y
Gan, K
Liu, K
Xu, B
Chen, M
AF Gao, Yue
Gan, Kai
Liu, Kuangzheng
Xu, Bin
Chen, Ming
TI SP1 Expression and the Clinicopathological Features of Tumors: A Meta-Analysis and Bioinformatics Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE specificity protein 1; cancer; clinicopathological characteristics; prognosis; biomarker
ID specificity protein 1; cancer; clinicopathological characteristics; prognosis; biomarker
AB Objective: Specificity protein 1 (SP1) plays a vital role to promote carcinogenesis in a variety of tumors, and its up-regulated expression is reported to be a hinter of poor prognosis of patients. We conducted this meta-analysis to elucidate the clinical significance and prognostic value of SP1 in malignant tumors. Methods: PubMed and Cochrane Library were searched for studies published between January 1, 2000 and June 1, 2020. The combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs)were used to investigate the correlation of SP1 with clinical behaviors and prognosis in patients with solid tumors. UALCAN was used to conduct bioinformatics analysis. Results: A total of 24 documents involving 2,739 patients were enrolled in our review. The random-effectmodel was used to perform this analysis due to the high level of heterogeneity. SP1 low expression was not conducive to lymph nodemetastasis (OR=0.42; 95% CI: 0.28-0.64; p < 0.05), progression of TNM stage (OR=0.34; 95% CI: 0.20-0.57; p < 0.05) and tumor infiltration (OR=0.33; 95% CI: 0.18-0.60; p < 0.05). Elevated SP1 expression was connected with shorter survival time of patients with hepatocellular carcinoma, pancreatic cancer, gastric cancer and esophageal cancer (HR=1.95; 95% CI: 1.16-3.28; p < 0.05). According to UALCAN database, breast cancer, ovarian cancer, colon cancer and lung adenocarcinoma display an elevated SP1 expression in comparison with normal tissues. Kaplan-Meier survival plots indicate SP1mRNA level has negative effects on prognosis of liver hepatocellular carcinoma and brain lower grade glioma. Conclusion: SP1 was associated with lymph node metastasis, TNM stage and depth of invasion, and indicated poor clinical outcome, which brought new insights on the potential candidacy of SP1 in clinical usage.
C1 [Gao, Yue] Medical School of Southeast University Nanjing, Institute of Urology, Surgical Research CenterJiangsu, China.
[Gan, Kai] Medical School of Southeast University Nanjing, Institute of Urology, Surgical Research CenterJiangsu, China.
[Liu, Kuangzheng] Medical School of Southeast University Nanjing, Institute of Urology, Surgical Research CenterJiangsu, China.
[Xu, Bin] Affiliated Zhongda Hospital of Southeast University, Department of UrologyJiangsu, China.
[Chen, Ming] Affiliated Zhongda Hospital of Southeast University, Department of UrologyJiangsu, China.
RP Chen, M (reprint author), Affiliated Zhongda Hospital of Southeast University, Department of Urology, Jiangsu, China.
EM mingchenseu@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 581998
EP 582009
DI 10.3389/pore.2021.581998
PG 12
ER
PT J
AU Xin, W
Zhao, Ch
Jiang, L
Pei, D
Zhao, L
Zhang, Ch
AF Xin, Wei
Zhao, Chaoran
Jiang, Longyang
Pei, Dongmei
Zhao, Lin
Zhang, Chengpu
TI Identification of a Novel Epithelial–Mesenchymal Transition Gene Signature Predicting Survival in Patients With HNSCC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epithelial-mesenchymal transition; HNSCC; mRNAs; Prognostic; survival
ID epithelial-mesenchymal transition; HNSCC; mRNAs; Prognostic; survival
AB Head and neck squamous cell cancer (HNSCC) is one of the most common types of cancer worldwide. There have beenmany reports suggesting that biomarkers explored via database mining plays a critical role in predicting HNSCC prognosis. However, a single biomarker for prognostic analysis is not adequate. Additionally, there is growing evidence indicating that gene signature could be a better choice for HNSCC prognosis. We performed a comprehensive analysis of mRNA expression profiles using clinical information of HNSCC patients from The Cancer Genome Atlas (TCGA). Gene Set Enrichment Analysis (GSEA) was performed, and we found that a set of genes involved in epithelial mesenchymal transition (EMT) contributed to HNSCC. Cox proportional regressionmodel was used to identify a fourgene (WIPF1, PPIB, BASP1, PLOD2) signature that were significantly associated with overall survival (OS), and all the four genes were significantly upregulated in tumor tissues. We successfully classified the patients with HNSCC into high-risk and low-risk groups, where in high-risk indicated poorer patient prognosis, indicating that this gene signature might be a novel potential biomarker for the prognosis of HNSCC. The prognostic ability of the gene signature was further validated in an independent cohort fromthe Gene Expression Omnibus (GEO) database. In conclusion, we identified a four-EMT-based gene signature which provides the potentiality to serve as novel independent biomarkers for predicting survival in HNSCC patients, as well as a new possibility for individualized treatment of HNSCC.
C1 [Xin, Wei] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Zhao, Chaoran] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Jiang, Longyang] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Pei, Dongmei] China Medical University, Shengjing Hospital, Department of Family MedicineShenyang, China.
[Zhao, Lin] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Zhang, Chengpu] China Medical University, Shengjing Hospital, Department of Family MedicineShenyang, China.
RP Zhang, Ch (reprint author), China Medical University, Shengjing Hospital, Department of Family Medicine, Shenyang, China.
EM zhangcp@sj-hospital.org
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 585192
EP 585205
DI 10.3389/pore.2021.585192
PG 14
ER
PT J
AU Wang, X
Liu, Sh
Cao, H
Li, X
Rong, Y
Liu, G
Du, H
Shen, H
AF Wang, Xiaopai
Liu, Shousheng
Cao, Huijiao
Li, Xiubo
Rong, Yuming
Liu, Guorong
Du, Hong
Shen, Hong
TI Increasing Embryonic Morphogen Nodal Expression Suggests Malignant Transformation in Colorectal Lesions and as a Potential Marker for CMS4 Subtype of Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Nodal; TGF-β; colorectal cancer; CMS-4; tumor-stroma percentage
ID Nodal; TGF-β; colorectal cancer; CMS-4; tumor-stroma percentage
AB Nodal, an embryonic morphogen in TGF-β family, is related with tumorigenicity and progression in various tumors including colorectal cancer (CRC). However, the difference of Nodal expression between CRC and colorectal polyps has not yet been investigated. Besides, whether Nodal can be used as a marker for consensus molecular subtype classification-4 (CMS4) of CRC is also worth studying. We analyzed Nodal expression in patients of CRC (161), high-grade intraepithelial neoplasia (HGIN, 28) and five types of colorectal polyps (116). The Nodal expression difference among groups and the association between Nodal expression and clinicopathological features were analyzed. Two categories logistic regression model was used to predict the odds ratio (OR) of risk factors for high tumor-stroma percentage (TSP), and ROC curve was used to assess the diagnostic value of Nodal in predicting high TSP in CRC. We found that Nodal expression was significantly elevated in CRC and HGIN (p < 0.0001). The increased expression of Nodal was related with high TSP, mismatch repair-proficient (pMMR) status, lymph node metastasis and advanced AJCC stage (p < 0.05). Besides, Nodal expression was the only risk factor for high TSP (OR=6.94; p < 0.001), and ROC curve demonstrated that Nodal expression was able to efficiently distinguish high and low TSP. In conclusion, different expression of Nodal between CRC/HGIN and benign lesions is suggestive of a promoting role for Nodal in colorectal tumor progression. Besides, Nodal might also be used as a potential marker for CMS4 subtype of CRC.
C1 [Wang, Xiaopai] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
[Liu, Shousheng] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of General MedicineGuangzhou, China.
[Cao, Huijiao] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of General MedicineGuangzhou, China.
[Li, Xiubo] South China University of Technology, School of Medicine, Guangzhou First People’s Hospital, Department of PathologyGuangzhou, China.
[Rong, Yuming] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of General MedicineGuangzhou, China.
[Liu, Guorong] South China University of Technology, School of Medicine, Guangzhou First People’s Hospital, Department of PathologyGuangzhou, China.
[Du, Hong] South China University of Technology, School of Medicine, Guangzhou First People’s Hospital, Department of PathologyGuangzhou, China.
[Shen, Hong] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
RP Shen, H (reprint author), Southern Medical University, College of Basic Medicine, Department of Pathology, Guangzhou, China.
EM shenhong2010168@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 587029
EP 587035
DI 10.3389/pore.2021.587029
PG 7
ER
PT J
AU Qian, C
Yang, Y
Lan, T
Wang, Y
Yao, J
AF Qian, Cuijuan
Yang, Yisheng
Lan, Tianchen
Wang, Yichao
Yao, Jun
TI Hsa_circ_0043265 Restrains Cell Proliferation, Migration and Invasion of Tongue Squamous Cell Carcinoma via Targeting the miR-1243/SALL1 Axis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE circ_0043265; miR-1243; SALL1; circRNAs; tongue squamous cell carcinoma
ID circ_0043265; miR-1243; SALL1; circRNAs; tongue squamous cell carcinoma
AB Increasing evidence has displayed critical roles of circular RNAs (circRNAs) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0043265 (circ_0043265) has been identified as a tumor suppressor in various tumors. Nevertheless, the critical roles of circ_0043265 in the initiation and progression of TSCC are yet to be fully elucidated. In our study, RNA and protein expressions were detected via qRT-PCR and Western blot. Cell proliferation, migration and invasion were evaluated via CCK-8 and transwell assays. The interactions between circ_0043265, miR-1243 and SALL1 were analyzed via bioinformatics analyses, RNA pull-down and luciferase assays, respectively. The current study demonstrated that circ_0043265 expression was downmodulated in TSCC tissues and cell lines (SCC25, SCC15, SCC9 and Cal27). Functionally, circ_0043265 overexpression led to an attenuation of cell proliferation, migration and invasion of SCC25 and Cal27 cells. Mechanistically, circ_0043265 acted as a competing endogenous RNA (ceRNA) via competitively sponging miR-1243, and restoration of miR-1243 rescued the inhibitory effects of circ_0043265 on cell proliferation, migration and invasion of SCC25 and Cal27 cells. Finally, it was observed that spalt like transcription factor 1 (SALL1), a potential target of miR-1243, was positively modulated via circ_0043265 in SCC25 and Cal27 cells, and SALL1 knockdown reversed the inhibitory effects of circ_0043265 on SCC25 and Cal27 cells. Collectively, the current study demonstrated that circ_0043265 was downmodulated in TSCC and was identified as a ceRNA that restrained the cell proliferation, migration and invasion of SCC25 and Cal27 cells via modulating the miR-1243/SALL1 axis.
C1 [Qian, Cuijuan] Taizhou University, School of Medicine, Institute of TumorTaizhou, China.
[Yang, Yisheng] Taizhou University, School of Medicine, Institute of TumorTaizhou, China.
[Lan, Tianchen] Taizhou University, School of Medicine, Institute of TumorTaizhou, China.
[Wang, Yichao] Taizhou Municipal Hospital, Department of Clinical LaboratoryTaizhou, China.
[Yao, Jun] Taizhou University, School of Medicine, Institute of TumorTaizhou, China.
RP Yao, J (reprint author), Taizhou University, School of Medicine, Institute of Tumor, Taizhou, China.
EM yaojuntzu@yeah.net
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Ma, C., Wang, F., Han, B., Zhong, X., Si, F., Ye, J., et al., 2018). SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex. Mol. Canc. 17, 78., DOI 10.1186/s12943-018-0824-y
Mu, X., Mou, K. H., Ge, R., Han, D., Zhou, Y., andWang, L. J., 2019). Linc00961 inhibits the proliferation and invasion of skin melanoma by targeting the miR‑367/PTEN axis. Int. J. Oncol. 55, 708–720., DOI 10.3892/ijo.2019.4848
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 587130
EP 587141
DI 10.3389/pore.2021.587130
PG 12
ER
PT J
AU Zhang, P
Feng, J
Wu, X
Chu, W
Zhang, Y
Li, P
AF Zhang, Peng
Feng, Jing
Wu, Xue
Chu, Weike
Zhang, Yilian
Li, Ping
TI Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE China; hepatocellular carcinoma; differentially expressed genes; hub genes; cell cycle; bioinformatics analysis
ID China; hepatocellular carcinoma; differentially expressed genes; hub genes; cell cycle; bioinformatics analysis
AB Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes’ protein expression levels. Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.
C1 [Zhang, Peng] Tianjin Medical University, School of GraduatesTianjin, China.
[Feng, Jing] Tianjin Medical University, School of GraduatesTianjin, China.
[Wu, Xue] Tianjin Medical University, School of GraduatesTianjin, China.
[Chu, Weike] Tianjin Medical University, School of GraduatesTianjin, China.
[Zhang, Yilian] Tianjin Medical University, School of GraduatesTianjin, China.
[Li, Ping] Tianjin Second People’s Hospital, Department of HepatologyTianjin, China.
RP Li, P (reprint author), Tianjin Second People’s Hospital, Department of Hepatology, Tianjin, China.
EM tjlplxg@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 588532
EP 588545
DI 10.3389/pore.2021.588532
PG 14
ER
PT J
AU Huang, R
Severson, E
Haberberger, J
Duncan, D
Hemmerich, A
Edgerly, C
Ferguson, Ly
Frampton, G
Owens, C
Williams, E
Elvin, J
Vergilio, JA
Killian, KJ
Lin, D
Morley, S
McEwan, D
Holmes, O
Danziger, N
Cohen, M
Sathyan, P
McGregor, K
Reddy, P
Venstrom, J
Anhorn, R
Alexander, B
Brown, Ch
Ross, J
Ramkissoon, Sh
AF Huang, S. P. Richard
Severson, Eric
Haberberger, James
Duncan, L. Daniel
Hemmerich, Amanda
Edgerly, Claire
Ferguson, Lynn N.
Frampton, Garrett
Owens, Clarence
Williams, Erik
Elvin, Julia
Vergilio, Jo-Anne
Killian, Keith Jonathan
Lin, Douglas
Morley, Samantha
McEwan, Deborah
Holmes, Oliver
Danziger, Natalie
Cohen, B. Michael
Sathyan, Pratheesh
McGregor, Kimberly
Reddy, Prasanth
Venstrom, Jeffrey
Anhorn, Rachel
Alexander, Brian
Brown, Charlotte
Ross, S. Jeffrey
Ramkissoon, H. Shakti
TI Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarkers; non-small cell lung cancer; comprehensive genomic profiling; PD-L1; immunohistochemistry
ID biomarkers; non-small cell lung cancer; comprehensive genomic profiling; PD-L1; immunohistochemistry
AB Comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) are important biomarker tools used for patients with non-small cell lung cancer (NSCLC) given the expanding number of standard-of-care therapies that require companion diagnostic testing. We examined 9450 NSCLC real-world patient samples that underwent both CGP and programmed death-ligand 1 (PD-L1) IHC to understand the biomarker landscape in this patient cohort. By assessing National Comprehensive Cancer Network (NCCN)-recommended biomarkers including genomic alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (Tumor Proportion Score (TPS) ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results for 70.5% of the 9,450 patients with NSCLC. Among the remaining 29.5% (2,789/9,450) of patients, 86.7% (2,419/2,789) were potentially eligible for another biomarker-associated therapy and/or clinical trial based on their genomic profile. In addition, in the PD-L1TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PDL1TPS< 50%, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.
C1 [Huang, S. P. Richard] Foundation Medicine, Inc.Morrisville, NC, USA.
[Severson, Eric] Foundation Medicine, Inc.Morrisville, NC, USA.
[Haberberger, James] Foundation Medicine, Inc.Morrisville, NC, USA.
[Duncan, L. Daniel] Foundation Medicine, Inc.Morrisville, NC, USA.
[Hemmerich, Amanda] Foundation Medicine, Inc.Morrisville, NC, USA.
[Edgerly, Claire] Foundation Medicine, Inc.Morrisville, NC, USA.
[Ferguson, Lynn N.] Foundation Medicine, Inc.Morrisville, NC, USA.
[Frampton, Garrett] Foundation Medicine, Inc.Cambridge, MA, USA.
[Owens, Clarence] Foundation Medicine, Inc.Morrisville, NC, USA.
[Williams, Erik] Foundation Medicine, Inc.Cambridge, MA, USA.
[Elvin, Julia] Foundation Medicine, Inc.Cambridge, MA, USA.
[Vergilio, Jo-Anne] Foundation Medicine, Inc.Cambridge, MA, USA.
[Killian, Keith Jonathan] Foundation Medicine, Inc.Cambridge, MA, USA.
[Lin, Douglas] Foundation Medicine, Inc.Cambridge, MA, USA.
[Morley, Samantha] Foundation Medicine, Inc.Cambridge, MA, USA.
[McEwan, Deborah] Foundation Medicine, Inc.Cambridge, MA, USA.
[Holmes, Oliver] Foundation Medicine, Inc.Cambridge, MA, USA.
[Danziger, Natalie] Foundation Medicine, Inc.Cambridge, MA, USA.
[Cohen, B. Michael] Wake Forest School of Medicine, Wake Forest Comprehensive Cancer CenterWinston-Salem, NC, USA.
[Sathyan, Pratheesh] Foundation Medicine, Inc.Cambridge, MA, USA.
[McGregor, Kimberly] Foundation Medicine, Inc.Cambridge, MA, USA.
[Reddy, Prasanth] Foundation Medicine, Inc.Cambridge, MA, USA.
[Venstrom, Jeffrey] Foundation Medicine, Inc.Cambridge, MA, USA.
[Anhorn, Rachel] Foundation Medicine, Inc.Cambridge, MA, USA.
[Alexander, Brian] Foundation Medicine, Inc.Cambridge, MA, USA.
[Brown, Charlotte] Foundation Medicine, Inc.Morrisville, NC, USA.
[Ross, S. Jeffrey] Foundation Medicine, Inc.Morrisville, NC, USA.
[Ramkissoon, H. Shakti] Foundation Medicine, Inc.Morrisville, NC, USA.
RP Huang, R (reprint author), Foundation Medicine, Inc., Morrisville, USA.
EM rhuang@foundationmedicine.com
CR Society, AC. Cancer Facts and figures. Atlanta, GA: American Cancer Society Inc., 2019).
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 592997
EP 593002
DI d10.3389/pore.2021.592997
PG 6
ER
PT J
AU Cai, Shz
Xiong, Qw
Zhao, Ln
Ji, Yt
Luo, Zx
Ma, Zr
AF Cai, Shi-zhong
Xiong, Qian-wei
Zhao, Li-na
Ji, Yi-ting
Luo, Zheng-xiang
Ma, Zhou-rui
TI β-Elemene Triggers ROS-dependent Apoptosis in Glioblastoma Cells Through Suppressing STAT3 Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE β-elemene; glioblastoma; apoptosis; stat3; ROS
ID β-elemene; glioblastoma; apoptosis; stat3; ROS
AB Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. β-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in β-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that β-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with β-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that β-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of p-JAK2 and p-Src. Moreover, pre-incubation of cells with ROS inhibitor N-acetyl-L-cysteine (NAC) significantly reversed β-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of β-elemene in glioblastoma cells.
C1 [Cai, Shi-zhong] Children’s Hospital of Soochow University, Department of Child and Adolescent HealthcareSuzhou, China.
[Xiong, Qian-wei] Children’s Hospital of Soochow University, Department of SurgerySuzhou, China.
[Zhao, Li-na] The First Affiliated Hospital of Soochow University, Key Laboratory of Clinical Immunology of Jiangsu ProvinceSuzhou, China.
[Ji, Yi-ting] Children’s Hospital of Soochow University, Department of Child and Adolescent HealthcareSuzhou, China.
[Luo, Zheng-xiang] Nanjing Brain Hospital Affiliated to Nanjing Medical University, Department of NeurosurgeryNanjing, China.
[Ma, Zhou-rui] Children’s Hospital of Soochow University, Department of SurgerySuzhou, China.
RP Ma, Zr (reprint author), Children’s Hospital of Soochow University, Department of Surgery, Suzhou, China.
EM chngrey@suda.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 594299
EP 594306
DI 10.3389/pore.2021.594299
PG 8
ER
PT J
TI Upregulation of Fatty Acid Transporters is Associated With Tumor Progression in Non-Muscle-Invasive Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bladder cancer; Fatty acid; FATP4; CD36; ACSL1
ID bladder cancer; Fatty acid; FATP4; CD36; ACSL1
AB As patients with non-muscle-invasive bladder cancer (NMIBC) show a high degree of heterogeneity in tumor recurrence or progression, many clinicians demand a detailed risk stratification. Although modified fatty acid metabolism in cancer cells is reported to reflect malignant phenotypes such as metastasis, the impact of fatty acid transporters on NMIBC has never been investigated. This study examined the clinicopathologic implications of fatty acid transporters such as fatty acid transport protein 4 (FATP4), cluster of differentiation 36/fatty acid translocase (CD36/FAT), and long chain acyl CoA synthetase 1 (ACSL1) in 286 NMIBC cases. This study revealed that FATP4, CD36, and ACSL1 were overexpressed in 123 (43.0%), 43 (15.0%), and 35 (12.2%) NMIBC cases, respectively. High FATP4 in tumor cells was associated with high grade (p = 0.004) and high stage (p = 0.039). High CD36 was related to high grade (p < 0.001), high stage (p = 0.002), and non-papillary growth type (p = 0.004). High ACSL1 showed an association with high grade (p < 0.001), high stage (p = 0.01), non-papillary growth type (p = 0.002), and metastasis (p = 0.033). High FATP4 was an independent factor predicting short overall survival (OS) (hazard ratio = 3.32; 95% confidence interval, 1.07–10.31; p = 0.038). In conclusion, upregulation of FATP4, CD36, and ACSL1 might promote the NMIBC progression and could be exploited in clinical risk stratification and targeted therapy.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 594705
EP 594710
DI 10.3389/pore.2021.594705
PG 6
ER
PT J
AU Wang, Y
Ji, N
Wang, J
Cao, J
Li, D
Zhang, Y
Zhang, L
AF Wang, Yi
Ji, Nan
Wang, Junmei
Cao, Jingli
Li, Deling
Zhang, Yang
Zhang, Liwei
TI SCG3 Protein Expression in Glioma Associates With less Malignancy and Favorable Clinical Outcomes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SCG3; glioma; clinicopathological features; prognosis
ID SCG3; glioma; clinicopathological features; prognosis
AB Introduction: Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors. However, there is no report on SCG3 protein expression in gliomas. Methods: The method of immunohistochemical staining on a glioma tissue microarray was utilized to detect SCG3 protein expression and investigate the correlations of its expression with clinicopathological and genetic features in gliomas. The RNA-seq data of SCG3 in The Cancer Genome Atlas database was exploited to explore these correlations at the transcriptional level. Results: There were 57.5% (130/226) glioma cases having SCG3 cytoplasmic staining in the tissue microarray. SCG3 expression inversely correlated with malignancy grade at both transcriptional and protein levels. The highest level was observed in oligodendroglial tumors, especially in oligodendrogliomas (ODs) with IDH-mutation/1p19q-codeletion. The lowest SCG3 expression was observed in glioblastomas (GBMs), especially in the mesenchymal subtype. Nearly a half of GBM cases (44.4%, 64/144) had any discernible SCG3 staining, and were defined as SCG3-positive by the microarray study. SCG3-positive GBM cases exhibited improved overall survival as compared with the SCG3-negative cases (29.3 vs. 14.5 months; Hazard ratio, 0.364; 95% CI, 0.216–0.612; p < 0.001). A multivariate Cox regression analysis also revealed SCG3 positivity as an independent favorable prognosticator in GBM patients. Conclusion: SCG3 protein expression inversely correlates with glioma malignancy and predicts favorable outcomes in GBM patients.
C1 [Wang, Yi] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Ji, Nan] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Wang, Junmei] Capital Medical University, Beijing Neurosurgical Institute, Department of PathologyBeijing, China.
[Cao, Jingli] Capital Medical University, Beijing Tiantan Hospital, Beijing Key Laboratory of Translational Medicine for Cerebrovascular DiseaseBeijing, China.
[Li, Deling] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Zhang, Yang] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Zhang, Liwei] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
RP Zhang, Y (reprint author), Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological Diseases, Beijing, China.
EM zhangyang8025@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 594931
EP 594939
DI 10.3389/pore.2021.594931
PG 9
ER
PT J
AU Wang, L
Li, X
Zhao, L
Jiang, L
Song, X
Qi, A
Chen, T
Ju, M
Hu, B
Wei, M
He, M
Zhao, L
AF Wang, Lin
Li, Xueping
Zhao, Lan
Jiang, Longyang
Song, Xinyue
Qi, Aoshuang
Chen, Ting
Ju, Mingyi
Hu, Baohui
Wei, Minjie
He, Miao
Zhao, Lin
TI Identification of DNA-Repair-Related Five-Gene Signature to Predict Prognosis in Patients with Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognostic biomarkers; DNA repair; overall survival; esophageal cancer; small molecular drugs; targeted therapy
ID prognostic biomarkers; DNA repair; overall survival; esophageal cancer; small molecular drugs; targeted therapy
AB Esophageal cancer (ESCA) is a leading cause of cancer-related mortality, with poor prognosis worldwide. DNA damage repair is one of the hallmarks of cancer. Loss of genomic integrity owing to inactivation of DNA repair genes can increase the risk of cancer progression and lead to poor prognosis. We aimed to identify a novel gene signature related to DNA repair to predict the prognosis of ESCA patients. Based on gene expression profiles of ESCA patients from The Cancer Genome Atlas and gene set enrichment analysis, 102 genes related to DNA repair were identified as candidates. After stepwise Cox regression analysis, we established a five-gene prognostic model comprising DGCR8, POM121, TAF9, UPF3B, and BCAP31. Kaplan-Meier survival analysis confirmed a strong correlation between the prognostic model and survival. Moreover, we verified the clinical value of the prognostic signature under the influence of different clinical parameters. We found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. In summary, our study provides a novel and promising prognostic signature based on DNA-repair-related genes to predict survival of patients with ESCA. Systematic data mining provides a theoretical basis for further exploring the molecular pathogenesis of ESCA and identifying therapeutic targets.
C1 [Wang, Lin] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Li, Xueping] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Zhao, Lan] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Jiang, Longyang] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Song, Xinyue] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Qi, Aoshuang] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Chen, Ting] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Ju, Mingyi] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Hu, Baohui] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Wei, Minjie] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[He, Miao] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Zhao, Lin] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
RP He, M (reprint author), China Medical University, School of Pharmacy, Department of Pharmacology, Shenyang, China.
EM hemiao_cmu@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 596899
EP 596911
DI 10.3389/pore.2021.596899
PG 13
ER
PT J
AU Chalela, R
Gonzalez-Garcia, GJ
Khilzi, K
Curull, V
Sanchez-Font, A
Longaron, R
Rodrigo-Calvo, TM
Martin-Ontiyuelo, C
Gea, J
Bellosillo, B
AF Chalela, Roberto
Gonzalez-Garcia, Gregorio Jose
Khilzi, Karys
Curull, Victor
Sanchez-Font, Albert
Longaron, Raquel
Rodrigo-Calvo, Teresa Maria
Martin-Ontiyuelo, Clara
Gea, Joaquim
Bellosillo, Beatriz
TI EGFR and KRAS Mutations in Lung Parenchyma of Subjects With EGFR/ KRAS Wild-Type Lung Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE adenocacinoma lung; driver mutation; EGFR–epidermal growth factor receptor; KRAS; Prognosis
ID adenocacinoma lung; driver mutation; EGFR–epidermal growth factor receptor; KRAS; Prognosis
AB The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically “healthy cells”. Objective: to demonstrate the presence of EGFR or KRAS mutations in non-tumoral lung cells in subjects with ADC and negative mutational status. Results: mutations in EGFR or KRAS oncogenes were identified in the normal lung in 9.7% of the subjects. Exon 21 substitution L858R in EGFR was detected in two cases while the exon 19 deletion E746-A750 in the EGFR, the G12C and G12D substitutions in the KRAS were detected once. One patient presented three different mutations in the normal lung parenchyma (EGFR_L858R, KRAS_G12C and KRAS_G12D). The negative-mutation status of the tumor and the mutations detected in the “normal lung” were confirmed using highly sensitive and specific TaqMan PCR (CAST-PCR). No differences were found in terms of progression, progression-free survival or overall survival during the 18 months follow-up. Conclusions: These results confirm the presence of driver mutations in the histologically normal lung parenchyma cells in the absence of mutations coexisting with the primary tumor.
C1 [Chalela, Roberto] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Gonzalez-Garcia, Gregorio Jose] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Khilzi, Karys] Hospital del Mar PSMAR, Respiratory Medicine DepartmentBarcelona, Spain.
[Curull, Victor] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Sanchez-Font, Albert] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Longaron, Raquel] Hospital del Mar PSMAR, Pathology DepartmentBarcelona, Spain.
[Rodrigo-Calvo, Teresa Maria] Hospital del Mar PSMAR, Pathology DepartmentBarcelona, Spain.
[Martin-Ontiyuelo, Clara] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Gea, Joaquim] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
[Bellosillo, Beatriz] Hospital delMar Medical Research Institute (IMIM)Barcelona, Spain.
RP Chalela, R (reprint author), Hospital delMar Medical Research Institute (IMIM), Barcelona, Spain.
EM rchalela@psmar.cat
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 598292
EP 598297
DI 10.3389/pore.2021.598292
PG 6
ER
PT J
AU Chen, M
Nie, Z
Cao, H
Gao, Y
Wen, X
Zhang, Ch
Zhang, Sh
AF Chen, Mei
Nie, Zhenyu
Cao, Hui
Gao, Yuanhui
Wen, Xiaohong
Zhang, Chong
Zhang, Shufang
TI Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Rac3; bladder cancer; TCGA; GSEA; prognose; clinicopathological significance
ID Rac3; bladder cancer; TCGA; GSEA; prognose; clinicopathological significance
AB Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear. Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA). Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues. Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.
C1 [Chen, Mei] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
[Nie, Zhenyu] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
[Cao, Hui] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
[Gao, Yuanhui] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
[Wen, Xiaohong] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
[Zhang, Chong] Central South University, Affiliated Haikou Hospital of Xiangya Medical College, UrologyHaikou, China.
[Zhang, Shufang] Central South University, Affiliated Hai Kou Hospital, Xiangya Medical College, Central LaboratoryHaikou, China.
RP Zhang, Ch (reprint author), Central South University, Affiliated Haikou Hospital of Xiangya Medical College, Urology, Haikou, China.
EM 763954234@qq.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 598460
EP 598468
DI 10.3389/pore.2021.598460
PG 9
ER
PT J
AU Kato, KM
Yoshida, H
Tanase, Y
Uno, M
Ishikawa, M
Kato, T
AF Kato, Kobayashi Mayumi
Yoshida, Hiroshi
Tanase, Yasuhito
Uno, Masaya
Ishikawa, Mitsuya
Kato, Tomoyasu
TI Loss of ARID1A Expression as a Favorable Prognostic Factor in Early-Stage Grade 3 Endometrioid Endometrial Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE endometrioid endometrial carcinoma; grade 3; prognosis; ARID1A; p53; mismatch repair
ID endometrioid endometrial carcinoma; grade 3; prognosis; ARID1A; p53; mismatch repair
AB Introduction: High-risk patients with grade 3 endometrioid endometrial carcinoma (G3EEC) who require adjuvant therapy have not been clearly identified. Therefore, the current study aimed to investigate the prognostic impact of ARID1A, p53, and mismatch repair (MMR) protein expressions, previously reported as prognosticators in some gynecological cancers, in patients with early-stage G3EEC. Methods: A total of 67 patients with pathologically confirmed early-stage G3EEC diagnosed between 1997 and 2020 were identified; none received adjuvant chemotherapy. The recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with a log-rank test. The protein expressions of ARID1A, p53, and MMR were examined via immunohistochemistry, and the associations between these biomarkers and clinical outcomes were evaluated. Results: Recurrence was observed in 9 (13%) of the 67 patients with early stage G3EEC. The respective 5-years RFS and OS rates were 87.7% and 93.7%, and 68.6%and 85.7%, respectively for stages I and II. Multivariate analysis showed significantly longer RFS among patients with ARID1A loss (hazard ratio = 8.7; 95% CI, 1.09–69.6, p = 0.04). No significant differences were observed in RFS and OS of patients according to p53 and MMR expression status. Conclusion: ARID1A expression status was a prognosticator for patients with early stage G3EEC without adjuvant therapy, whereas p53 and MMR expression status showed no impact on survival outcomes. ARID1A may become a useful biomarker for stratification of adjuvant treatment for early stage G3EEC patients.
C1 [Kato, Kobayashi Mayumi] National Cancer Center Hospital, Department of GynecologyTokyo, Japan.
[Yoshida, Hiroshi] National Cancer Center Hospital, Department of Diagnostic PathologyTokyo, Japan.
[Tanase, Yasuhito] National Cancer Center Hospital, Department of GynecologyTokyo, Japan.
[Uno, Masaya] National Cancer Center Hospital, Department of GynecologyTokyo, Japan.
[Ishikawa, Mitsuya] National Cancer Center Hospital, Department of GynecologyTokyo, Japan.
[Kato, Tomoyasu] National Cancer Center Hospital, Department of GynecologyTokyo, Japan.
RP Kato, KM (reprint author), National Cancer Center Hospital, Department of Gynecology, Tokyo, Japan.
EM maykobay@ncc.go.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 598550
EP 598558
DI 10.3389/pore.2021.598550
PG 9
ER
PT J
AU Huang, X
Xu, J
Wu, Y
Sheng, L
Li, Y
Zha, B
Sun, T
Yang, J
Zang, Sh
Liu, J
AF Huang, Xinmei
Xu, Jiong
Wu, Yueyue
Sheng, Li
Li, Yue
Zha, Bingbing
Sun, Tiange
Yang, Ju
Zang, Shufei
Liu, Jun
TI Alterations in CD8+ Tregs, CD56+ Natural Killer Cells and IL-10 Are Associated With Invasiveness of Nonfunctioning Pituitary Adenomas (NFPAs)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE invasive nonfunctioning pituitary adenomas; immune tolerance; CD8+ tregs; natural killer cells; IL-10
ID invasive nonfunctioning pituitary adenomas; immune tolerance; CD8+ tregs; natural killer cells; IL-10
AB Invasive nonfunctioning pituitary adenomas (NFPAs) grow rapidly and the mechanisms are unclear. Among many complex mechanisms, the role of immunity in the development of NFPAs has not been fully explored. Here, we analyzed the clinical features 146 NFPA patients who underwent trans-sphenoidal surgery or craniotomy and examined the effects of immune tolerance in invasiveness of NFPA patients using fluorescence-activated cell sorting and immunohistochemical methods. We found patients with invasive NFPAs had more visual deficits and defective fields, higher tumor size, and lower white blood cell count compared with patients with noninvasive NFPAs. Additionally, compared with patients with noninvasive NFPAs, patients with invasive NFPAs had conspicuously lower CD3−CD56+ natural killer (NK) cells and significantly higher levels of CD3+CD8+CD28-T cells (CD8+ Tregs) and interleukin-10 (IL-10) in peripheral blood. Moreover, patients with invasive NFPAs had lower infiltrated CD56+ cells, less infiltrated CD28+ cells, and significantly greater IL-10 expression. These results demonstrated that low CD56+ cells infiltration and CD28+ cells infiltration, as well as high IL-10 expression in pituitary tumor tissues, were related with increased invasiveness of NFPAs. Levels of CD3−CD56+ NK cells, CD8+ Tregs and IL-10 in the peripheral blood could be feasible diagnostic markers for invasive NFPAs.
C1 [Huang, Xinmei] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Xu, Jiong] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Wu, Yueyue] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Sheng, Li] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Li, Yue] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Zha, Bingbing] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Sun, Tiange] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Yang, Ju] Fudan University, The Fifth People’s Hospital of Shanghai, Department of PathologyShanghai, China.
[Zang, Shufei] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
[Liu, Jun] Fudan University, The Fifth People’s Hospital of Shanghai, Department of EndocrinologyShanghai, China.
RP Zang, Sh (reprint author), Fudan University, The Fifth People’s Hospital of Shanghai, Department of Endocrinology, Shanghai, China.
EM zangshufei@sina.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 598887
EP 598895
DI 10.3389/pore.2021.598887
PG 9
ER
PT J
TI Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE autophagy; CUL4A; intrahepatic cholangiocarcinoma; prognosis; LC3II
ID autophagy; CUL4A; intrahepatic cholangiocarcinoma; prognosis; LC3II
AB CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B expression. Q-score was defined as the sum of the labeling intensity and proportion. The cut-off point for immunoreactivity was set. CUL4A was overexpressed in cell lines and autophagy reflux was compared after manipulation. The iCCA cases with CUL4A overexpression had significantly higher prevalence of intact activated autophagy (42.4 vs. 15.2%; p = 0.003), which was significantly associated with advance tumor stage (34.1%vs. 15.4%; p = 0.032), less extensive necrosis (8.3 vs. 49.3%; p < 0.001), and shortened disease-free survival (mean, 19.6 vs. 65.5months, p = 0.015). In vitro, iCCA cells with CUL4A overexpression significantly increased LC3II level as compared to the cells under basal condition. Although both cell types showed intact autophagy with increased LC3II expression after bafilomycin A1 treatment, the accumulation of LC3II was higher in CUL4A-overexpressing cells. CUL4A overexpression increased the proliferation of cells as compared with control cells. After treatment with bafilomycin A1, proliferation was inhibited in both cell types, but the effects were more prominent in the cells overexpressing CUL4A. CUL4A promotes autophagy, and exhibits significantly higher autophagic flux which affects the proliferation of iCCA cells; these effects correlated with advance tumor stage and poor prognosis. Thus, targeting autophagy may be potentially therapeutic in iCCA.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 602714
EP 602721
DI 10.3389/pore.2021.602714
PG 8
ER
PT J
AU Shen, GJ
Shen, J
Teng, YR
Wang, BL
Zhao, HW
Wang, ChQ
AF Shen, Guo Jian
Shen, Jun
Teng, Yue Rong
Wang, Bo Lin
Zhao, He Wen
Wang, Chuan Qin
TI High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GP73; gastric cancer; prognosis; neoadjuvant chemotherapy; pathological response
ID GP73; gastric cancer; prognosis; neoadjuvant chemotherapy; pathological response
AB Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.
C1 [Shen, Guo Jian] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
[Shen, Jun] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
[Teng, Yue Rong] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
[Wang, Bo Lin] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
[Zhao, He Wen] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
[Wang, Chuan Qin] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical OncologyHangzhou, China.
RP Wang, ChQ (reprint author), Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Surgical Oncology, Hangzhou, China.
EM wqctiger@zju.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 603838
EP 603843
DI 10.3389/pore.2021.603838
PG 6
ER
PT J
TI The Clinicopathological Significance of YAP/TAZ Expression in Hepatocellular Carcinoma with Relation to Hypoxia and Stemness
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hepatocellular carcinoma; Hippo pathway; hypoxia; stemness; immunohistochemistry
ID hepatocellular carcinoma; Hippo pathway; hypoxia; stemness; immunohistochemistry
AB Background/Aims: Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) activation has been implicated in hepatocarcinogenesis and hepatic progenitor cell differentiation, and hypoxia has been shown to induce nuclear translocation of YAP in cancer cells. Here, we aimed to investigate the relationship between hypoxia, YAP and TAZ expression and stemness-related marker expression in human hepatocellular carcinomas (HCCs) and its clinical implications. Methods: Immunohistochemical stains were performed on tissue microarrays from 305 surgically resected HCCs, and the expression status of YAP and TAZ were correlated with CAIX, stemness markers (K19, EpCAM) and epithelial-mesenchymal transition (EMT)-related markers (uPAR, ezrin). The clinicopathological significance of YAP/TAZ expression was analyzed with relation to CAIX expression status. Results: YAP and TAZ expression were seen in 13.4 and 4.3% of HCCs, respectively. YAP/TAZ-positive HCCs frequently demonstrated higher serum AFP levels, microvascular invasion, advanced tumor stage, increased proliferative activity and expression of stemness- and EMT-related markers, CAIX, p53 and Smad2/3 (p < 0.05, all). Interestingly, YAP/TAZ-positivity was associated with microvascular invasion, higher serum AFP levels, stemness and EMT-related marker expression only in tumors expressing CAIX (p < 0.05, all), while these associations were not seen in CAIXnegative HCCs. Conclusions: YAP/TAZ expression is associated with vascular invasion, stemness and EMT in HCCs with hypoxia marker expression. The effect of Hippo signaling pathway deregulation in HCC may depend on the presence or absence of a hypoxic microenvironment, and hypoxia marker expression status should be taken into account when considering the use of YAP/TAZ as markers of aggressive biologic behavior in HCC.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 604600
EP 604607
DI 10.3389/pore.2021.604600
PG 8
ER
PT J
AU Wojtukiewicz, M
Mysliwiec, M
Matuszewska, E
Sulkowski, S
Zimnoch, L
Politynska, B
Wojtukiewicz, A
Tucker, S
Honn, K
AF Wojtukiewicz, Z. Marek
Mysliwiec, Marta
Matuszewska, Elwira
Sulkowski, Stanislaw
Zimnoch, Lech
Politynska, Barbara
Wojtukiewicz, M. Anna
Tucker, C. Stephanie
Honn, V. Kenneth
TI Heterogeneous Expression of Proangiogenic and Coagulation Proteins in Gliomas of Different Histopathological Grade
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiogenesis; VEGF; bFGF; D-dimers; blood coagulation; fibrin; tissue factor; glial tumors 3
ID angiogenesis; VEGF; bFGF; D-dimers; blood coagulation; fibrin; tissue factor; glial tumors 3
AB Brain gliomas are characterized by remarkably intense invasive growth and the ability to create new blood vessels. Angiogenesis is a key process in the progression of these tumors. Coagulation and fibrinolysis factors play a role in promoting angiogenesis. The aim of the study was to evaluate the expression of proangiogenic proteins (VEGF and bFGF) and hemostatic proteins (TF, fibrinogen, fibrin, D-dimers) associated with neoplastic cells and vascular endothelial cells in brain gliomas of various degrees of malignancy. Immunohistochemical tests were performed using the ABC method with the use of mono- and polyclonal antibodies. The obtained results indicated that both neoplastic cells and vascular endothelial cells in gliomas of various degrees of malignancy are characterized by heterogeneous expression of proteins of the hemostatic system and angiogenesis markers. The strongest expression of proangiogenic factors and procoagulant factors was demonstrated in gliomas of higher-grade malignancy.
C1 [Wojtukiewicz, Z. Marek] Medical University of Bialystok, Department of OncologyBialystok, Poland.
[Mysliwiec, Marta] Medical University of Bialystok, Department of OncologyBialystok, Poland.
[Matuszewska, Elwira] Comprehensive Cancer Center of Bialystok, Department of Clinical OncologyBialystok, Poland.
[Sulkowski, Stanislaw] Medical University of Bialystok, Department of General PathomorphologyBialystok, Poland.
[Zimnoch, Lech] Medical University of Bialystok, Department of General PathomorphologyBialystok, Poland.
[Politynska, Barbara] Medical University of Bialystok, Department of Philosophy and Human PsychologyBialystok, Poland.
[Wojtukiewicz, M. Anna] Medical University of Bialystok, Department of Philosophy and Human PsychologyBialystok, Poland.
[Tucker, C. Stephanie] Wayne State University, Bioactive Lipids Research Program, Department of Pathology-School of MedicineDetroit, MI, USA.
[Honn, V. Kenneth] Wayne State University, Department of ChemistryDetroit, MI, USA.
RP Wojtukiewicz, M (reprint author), Medical University of Bialystok, Department of Oncology, Bialystok, Poland.
EM mzwojtukiewicz@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 605017
EP 605023
DI 10.3389/pore.2021.605017
PG 7
ER
PT J
AU Kamseng, P
Siriboonpiputtana, T
Puavilai, T
Chuncharunee, S
Paisooksantivatana, K
Chareonsirisuthigul, T
Junking, M
Chiraphapphaiboon, W
Yenchitsomanus, Pth
Rerkamnuaychoke, B
AF Kamseng, Parin
Siriboonpiputtana, Teerapong
Puavilai, Teeraya
Chuncharunee, Suporn
Paisooksantivatana, Karan
Chareonsirisuthigul, Takol
Junking, Mutita
Chiraphapphaiboon, Wannasiri
Yenchitsomanus, Pa-thai
Rerkamnuaychoke, Budsaba
TI Targeting UCHL1 Induces Cell Cycle Arrest in High-Risk Multiple Myeloma with t(4;14)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE UCHL1; t(4; 14) multiple myeloma; cell cycle regulation; biomarker; expression profile
ID UCHL1; t(4; 14) multiple myeloma; cell cycle regulation; biomarker; expression profile
AB Multiple myeloma (MM) patients considered to be at high cytogenetic risk commonly fail to respond to standard treatment. A thorough understanding of the molecular mechanism of MM development is, therefore, needed. We endeavored to explore the transcriptional signature among different subgroups of newly diagnosed MM using gene chip-based expression microarray. Bone marrow samples of 15 newly diagnosed Thai MM patients were included. The chromosomal translocation t(4;14) was the most frequently identified genetic alteration in the high-risk subgroup. Cluster analysis from expression profiling demonstrated that high-riskMMhave a distinctly different expression pattern compared to standard-risk patients. The most significant differentially expressed gene was UCHL1. Functional enrichment analysis by Gene Set Enrichment Analysis, FUNRICH, and Gene Ontology Panther pathway revealed the gene sets involved in cell cycle control to be enriched in the t(4;14) high-risk group. Interestingly, among the well-established downstream targets of UCHL1, only CCND2 was significantly expressed in the t(4;14) high-risk group. Suppression of UCHL1 protein level by LDN-5744 inhibitor could arrest the cell cycle in G1 phase in cell lines. These findings shed light on the molecular mechanism of UCHL1 in t(4;14) high-risk MM and support the evidence that alteration of the UCHL1 pathway may play a role in the pathogenesis of high-risk MM.
C1 [Kamseng, Parin] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of PathologyBangkok, Thailand.
[Siriboonpiputtana, Teerapong] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of PathologyBangkok, Thailand.
[Puavilai, Teeraya] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of MedicineBangkok, Thailand.
[Chuncharunee, Suporn] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of MedicineBangkok, Thailand.
[Paisooksantivatana, Karan] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of PathologyBangkok, Thailand.
[Chareonsirisuthigul, Takol] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of PathologyBangkok, Thailand.
[Junking, Mutita] Mahidol University, Faculty of Medicine Siriraj Hospital, Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT)Bangkok, Thailand.
[Chiraphapphaiboon, Wannasiri] Mahidol University, Faculty of Medicine Siriraj Hospital, Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT)Bangkok, Thailand.
[Yenchitsomanus, Pa-thai] Mahidol University, Faculty of Medicine Siriraj Hospital, Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT)Bangkok, Thailand.
[Rerkamnuaychoke, Budsaba] Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of PathologyBangkok, Thailand.
RP Rerkamnuaychoke, B (reprint author), Mahidol University, Faculty of Medicine Ramathibodi Hospital, Department of Pathology, Bangkok, Thailand.
EM budsaba.rer@mahidol.ac.th
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 606567
EP 606579
DI 10.3389/pore.2021.606567
PG 13
ER
PT J
AU Locsei, Z
Sebestyen, K
Sebestyen, Zs
Feher, E
Soltesz, D
Musch, Z
Mangel, CsL
AF Locsei, Zoltan
Sebestyen, Klara
Sebestyen, Zsolt
Feher, Eszter
Soltesz, Dorottya
Musch, Zoltan
Mangel, Csaba Laszlo
TI IMAT-IGRT Treatment with Simultaneous Integrated Boost as Dose Escalation for Patients with Cervical Cancer: A Single Institution, Prospective Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical cancer; SIB; IGRT; IMRT; dose escalation; toxicity 3
ID cervical cancer; SIB; IGRT; IMRT; dose escalation; toxicity 3
AB Purpose: The aim of this study was to introduce the simultaneous integrated boost (SIB) technique to assess the safety of replacement of the brachytherapy (BT) boost for ineligible patients with cervical cancer receiving radiochemotherapy (RCT). Methods: Fourteen patients were enrolled between 2015 and 2018. SIB was delivered using RapidArc technique at doses of 2.4 Gy per fraction during pelvic irradiation with 50.4/ 1.8 Gy in seven patients (to a total dose of 67.2 Gy) with limited volume disease. In 7 patients with a more advanced disease stage (>5 cm tumor, parametric invasion both sides), parametric boost therapy was added to the pelvic radiotherapy to a total dose of the macroscopic tumor of 79.2 Gy. All patients received simultaneous cisplatin-based chemotherapy for 5 cycles with a dosage of 40 mg/m2. We examined acute toxicity (CTCAE v4.1) and quality of life (EORTC QLQ30 and CX24). The tumor regression rate was evaluated with RECIST 1.1 after the first 3- to 4-months follow-up Magnetic Resonance Imaging (MRI) scan. We calculated the percentage of tumor regression rate and the local control during the follow-up period and evaluated the survival data. Results: Our patient data are presented at a median follow-up time of 24.5 months. During the treatment period, no grade 3 to 4 toxicity was observed. During the follow-up period, no late-onset toxicity was observed. The tumor regression rate at the first MRI scan was 95.31% on average. Disease free survival (DFS) during the median follow-up of 24 months was 98.6%. Conclusion: In patients with cervical cancer, the SIB technique is amenable as part of definitive RCT. Dose escalation with the SIB technique can be safely administered to cervical cancer patients during definitive RCT if BT is not feasible. However, further randomized clinical studies are needed to validate the method, so routine use of it cannot be recommended yet.
C1 [Locsei, Zoltan] University of Pecs, Department of OncologyPecs, Hungary.
[Sebestyen, Klara] University of Pecs, Department of OncologyPecs, Hungary.
[Sebestyen, Zsolt] University of Pecs, Department of OncologyPecs, Hungary.
[Feher, Eszter] Pecsi Diagnosztikai Kozpont Kft.Pecs, Hungary.
[Soltesz, Dorottya] University of Pecs, Department of OncologyPecs, Hungary.
[Musch, Zoltan] University of Pecs, Department of OncologyPecs, Hungary.
[Mangel, Csaba Laszlo] University of Pecs, Department of OncologyPecs, Hungary.
RP Locsei, Z (reprint author), University of Pecs, Department of Oncology, Pecs, Hungary.
EM locsei.zoltan@pte.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 608446
EP 608454
DI 10.3389/pore.2021.608446
PG 9
ER
PT J
AU Chen, H
Lin, X
Liu, H
Huang, Ch
Li, R
Ai, J
Wei, J
Xiao, Sh
AF Chen, Huoying
Lin, Xiaoying
Liu, Hongbo
Huang, Cheng
Li, Rong
Ai, Jie
Wei, Jiaxue
Xiao, Shengjun
TI HMGB1 Translocation is Associated with Tumor-Associated Myeloid Cells and Involved in the Progression of Fibroblastic Sarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE high-mobility group box 1 protein; translocation; sarcoma; tumor-associated macrophage; myeloid cell
ID high-mobility group box 1 protein; translocation; sarcoma; tumor-associated macrophage; myeloid cell
AB The morphological variability and genetic complexity of fibroblastic sarcoma makes its diagnosis and treatment a challenge. High-mobility group box 1 protein (HMGB1), which functions as a DNA chaperone and a prototypical damage-associated molecular pattern, plays a paradoxical role in cancer. However, the expression pattern and role of HMGB1 in fibroblastic sarcomas is ill defined. By immunostaining of 95 tissue microarray cores of fibroblastic sarcomas, HMGB1 was found to be expressed in most tumor tissues. Nuclear HMGB1 translocation to cytoplasm was observed both in tumor cells and vascular endothelial cells. A visible number of tumor-associated myeloid cells including CD68+ and CD163+ macrophages and CD33+ myeloid cells were also detected in most tumor tissues. HMGB1 translocation was not only associated with CD68, CD163, and CD33 density, but also with disease progression. These results imply that HMGB1, an important regulator of the tumor microenvironment, is associated with tumor-associated myeloid cells and involved in the progression of fibroblastic sarcomas; HMGB1 may serve as a promising prognostic biomarker and a potential therapeutic target for fibroblastic sarcoma.
C1 [Chen, Huoying] Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Prenatal Diagnosis CenterGuangzhou, China.
[Lin, Xiaoying] Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Prenatal Diagnosis CenterGuangzhou, China.
[Liu, Hongbo] The Second Affiliated Hospital of Guilin Medical University, Department of Laboratory MedicineGuilin, China.
[Huang, Cheng] Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Prenatal Diagnosis CenterGuangzhou, China.
[Li, Rong] Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Prenatal Diagnosis CenterGuangzhou, China.
[Ai, Jie] The Second Affiliated Hospital of Guilin Medical University, Department of Laboratory MedicineGuilin, China.
[Wei, Jiaxue] Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Prenatal Diagnosis CenterGuangzhou, China.
[Xiao, Shengjun] The Second Affiliated Hospital of Guilin Medical University, Department of PathologyGuilin, China.
RP Xiao, Sh (reprint author), The Second Affiliated Hospital of Guilin Medical University, Department of Pathology, Guilin, China.
EM xiaoshengjun@glmc.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 608582
EP 608590
DI 10.3389/pore.2021.608582
PG 9
ER
PT J
AU Feng, D
Lin, J
Wang, W
Yan, K
Liang, H
Liang, J
Yu, H
Ling, B
AF Feng, Dingqing
Lin, Jie
Wang, Wenhui
Yan, Keqin
Liang, Haiyan
Liang, Jing
Yu, Huan
Ling, Bin
TI Wnt3a/β-Catenin/CBP Activation in the Progression of Cervical Intraepithelial Neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical intraepithelial neoplasia; wnt signaling; CBP; Piwil2; stemness; Differentiation
ID cervical intraepithelial neoplasia; wnt signaling; CBP; Piwil2; stemness; Differentiation
AB Piwil2 reprograms HPV-infected reserve cells in the cervix into tumor-initiated cells (TICs) and upregulates Wnt3a expression sequentially, which leads to cervical intraepithelial neoplasia (CIN) and ultimately squamous cell carcinoma (SCC). However, little is known regarding Wnt signaling in the maintenance of TIC stemness during the progression of cervical lesions. We herein investigated the expression of canonical Wnt3a signaling and related genes by microarray data set analysis and immunohistochemical (IHC) staining of samples obtained by biopsy of normal cervix, low- and high-grade CIN, and invasive SCC tissue. Array data analyzed by GEO2R showed higher expression levels of Wnt signaling and their target genes, significant upregulation of stemness-associated markers, and notably downregulated cell differentiation markers in CIN and SCC tissues compared with those in the normal cervix tissue. Further, Gene Set Enrichment Analysis (GSEA) revealed that Wnt pathway-related genes significantly enriched in SCC. IHC staining showed gradually increased immunoreactivity score of Wnt3a and CBP and notable translocation of β-catenin from the membrane to the cytoplasm and nucleus during the lesion progression. The intensity and proportion of P16, Ki67 and CK17 staining also increased with the progression of cervical lesions, whereas minimal to negative Involucrin expression was observed in CIN2/3 and SCC. Therefore, canonical Wnt signaling may contribute to the progression of CIN to SCC and may be a potential therapeutic target.
C1 [Feng, Dingqing] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Lin, Jie] China-Japan Friendship Hospital, Department of PathologyBeijing, China.
[Wang, Wenhui] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Yan, Keqin] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Liang, Haiyan] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Liang, Jing] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Yu, Huan] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Ling, Bin] China-Japan Friendship Hospital, Department of Obstetrics and GynecologyBeijing, China.
RP Ling, B (reprint author), China-Japan Friendship Hospital, Department of Obstetrics and Gynecology, Beijing, China.
EM lingbin.ling@vip.sina.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 609620
EP 609627
DI 10.3389/pore.2021.609620
PG 8
ER
PT J
AU Naso, J
Povshedna, T
Wang, G
Banyi, N
MacAulay, C
Ionescu, D
Zhou, Ch
AF Naso, R. Julia
Povshedna, Tetiana
Wang, Gang
Banyi, Norbert
MacAulay, Calum
Ionescu, N. Diana
Zhou, Chen
TI Automated PD-L1 Scoring for Non-Small Cell Lung Carcinoma Using Open-Source Software
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pathology; PD-L1; biomarker; non-small cell lung cancer; digital pathology
ID pathology; PD-L1; biomarker; non-small cell lung cancer; digital pathology
AB PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to immunotherapy, but scoring of PD-L1 immunohistochemistry shows considerable interobserver variability. Automated methods may allow more consistent and expedient PD-L1 scoring. We aimed to assess the technical concordance of PD-L1 scores produced using free open source QuPath software with the manual scores of three pathologists. A classifier for PD-L1 scoring was trained using 30 NSCLC image patches. A separate test set of 207 image patches from 69 NSCLC resection cases was used for comparison of automated and manual scores. Automated and average manual scores showed excellent correlation (concordance correlation coeffecient = 0.925), though automated scoring resulted in significantly more 1–49% scores than manual scoring (p = 0.012). At both 1% and 50% thresholds, automated scores showed a level of concordance with our ‘gold standard’ (the average of three pathologists’ manual scores) similar to that of individual pathologists. Automated scoring showed high sensitivity (95%) but lower specificity (84%) at a 1% threshold, and excellent specificity (100%) but lower sensitivity (71%) at a 50% threshold. We conclude that our automated PD-L1 scoring system for NSCLC has an accuracy similar to that of individual pathologists. The detailed protocol we provide for free open source scoring software and our discussion of the limitations of this technology may facilitate more effective integration of automated scoring into clinical workflows.
C1 [Naso, R. Julia] University of British Columbia, Department of PathologyVancouver, BC, Canada.
[Povshedna, Tetiana] BC Cancer, Department of PathologyVancouver, BC, Canada.
[Wang, Gang] BC Cancer, Department of PathologyVancouver, BC, Canada.
[Banyi, Norbert] BC Cancer, Department of PathologyVancouver, BC, Canada.
[MacAulay, Calum] British Columbia Cancer Research Center, Department of Integrative OncologyVancouver, BC, Canada.
[Ionescu, N. Diana] BC Cancer, Department of PathologyVancouver, BC, Canada.
[Zhou, Chen] BC Cancer, Department of PathologyVancouver, BC, Canada.
RP Zhou, Ch (reprint author), BC Cancer, Department of Pathology, Vancouver, Canada.
EM czhou@bccancer.bc.ca
CR Gong J, Chehrazi-Raffle A, Reddi S, Salgia R Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer, 2018). 6:8., DOI 10.1186/s40425-018-0316-z
Buttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. JCO, 2017). 35:3867–76., DOI 10.1200/jco.2017.74.7642
Tsao MS, Kerr KM, Kockx M, Beasley M-B, Borczuk AC, Botling J, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 Project. J Thorac Oncol, 2018). 13:1302–11., DOI 10.1016/j. jtho.2018.05.013
Brunnstrom H, Johansson A, Westbom-Fremer S, Backman M, Djureinovic D, Patthey A, et al. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Mod Pathol, 2017). 30:1411–21., DOI 10.1038/modpathol.2017.59
Ratcliffe MJ, Sharpe A, Midha A, Barker C, Scott M, Scorer P, et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res, 2017). 23:3585–91., DOI 10.1158/1078-0432.ccr-16-2375
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Kapil A, Meier A, Zuraw A, Steele KE, Rebelatto MC, Schmidt G, et al. Deep semi supervised generative learning for automated tumor proportion scoring on NSCLC tissue needle biopsies. Sci Rep, 2018). 8:17343., DOI 10.1038/s41598-018- 35501-5
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Bankhead P, Loughrey MB, Fernandez JA, Dombrowski Y,McArt DG, Dunne PD, et al. QuPath: open source software for digital pathology image analysis. Sci Rep, 2017). 7:16878., DOI 10.1038/s41598-017-17204-5
Humphries MP, Bingham V, Abdullahi Sidi F, Craig SG, McQuaid S, James J, et al. Improving the diagnostic accuracy of the PD-L1 test with image analysis and multiplex hybridization. Cancers, 2020). 12:1114., DOI 10.3390/ cancers12051114
Naso JR, Wang G, Banyi N, Derakhshan F, Shokoohi A, Ho C, et al., 2020). Comparability of Laboratory-Developed and Commercial PD-L1 Assays in Non-Small Cell Lung carcinoma. Annals of Diagnostic Pathology 50(1):151590., DOI 10.1016/j.anndiagpath.2020.151590
Cooper WA, Russell PA, Cherian M, Duhig EE, Godbolt D, Jessup PJ, et al. Intra- and interobserver reproducibility assessment of PD-L1 biomarker in non-small cell lung cancer. Clin Cancer Res, 2017). 23:4569–77., DOI 10.1158/ 1078-0432.ccr-17-0151
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Humphries MP, McQuaid S, Craig SG, Bingham V, Maxwell P, Maurya M, et al. Critical appraisal of programmed death ligand 1 reflex diagnostic testing: current standards and future opportunities. J Thorac Oncol, 2019). 14:45–53., DOI 10.1016/j.jtho.2018.09.025
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 609717
EP 609725
DI 10.3389/pore.2021.609717
PG 9
ER
PT J
AU Dai, J
Zhou, N
Wu, R
Du, J
Miao, Sh
Gong, K
Yang, L
Chen, W
Li, X
Li, Ch
Wu, Y
AF Dai, Juanjuan
Zhou, Ning
Wu, Rui
Du, Jing
Miao, Shuang
Gong, Kaikai
Yang, Lijuan
Chen, Weiwei
Li, Xuelin
Li, Chen
Wu, Yan
TI LncRNA MALAT1 Regulating Lung Carcinoma Progression via the miR-491-5p/UBE2C Axis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE MALAT1; miR-491-5p; UBE2C; lung carcinoma; proliferatiom
ID MALAT1; miR-491-5p; UBE2C; lung carcinoma; proliferatiom
AB Long noncoding RNAs (lncRNAs) play a critical role in the development of lung carcinoma. The mechanism of MALAT1 in lung carcinoma development is not understood very well. This study aimed to investigate the role of MALAT1 in lung carcinoma progression and the mechanism underlying the role of miR-491-5p in the MALAT1 mediated regulation of UBE2C expression. The results indicated that the expression of MALAT1 was often augmented in lung carcinoma cells. Suppression of MALAT1 blocked the proliferation, invasion and migration ability of cancer cells and inhibited the expression of UBE2C. UBE2C restoration attenuated the MALAT1 knockdown-induced anti-cancer effects. Moreover, UBE2C and MALAT1 were indicated as targets of miR-491-5p and inhibition of miR-491-5p restored the MALAT1 knockdown-induced inhibition of the progression of lung carcinoma. Furthermore, MALAT1 sponged miR-491-5p to upregulate UBE2C expression, causing it to act as a competing endogenous RNA. Collectively, MALAT1 downregulation suppressed lung carcinoma progression by regulating the miR-491-5p/UBE2C axis. These results indicate that MALAT1 could be a molecular target for lung carcinoma treatment and prognosis.
C1 [Dai, Juanjuan] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Zhou, Ning] Binzhou Medical University Hospital, Department of Otolaryngology Head and Neck SurgeryBinzhou, China.
[Wu, Rui] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Du, Jing] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Miao, Shuang] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Gong, Kaikai] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Yang, Lijuan] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Chen, Weiwei] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Li, Xuelin] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
[Li, Chen] Binzhou Medical University Hospital, Institute for Metabolic and Neuropsychiatric DisordersBinzhou, China.
[Wu, Yan] Binzhou Medical University Hospital, Cancer Research InstituteBinzhou, China.
RP Wu, Y (reprint author), Binzhou Medical University Hospital, Cancer Research Institute, Binzhou, China.
EM wuyan55@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 610159
EP 610168
DI 10.3389/pore.2021.610159
PG 10
ER
PT J
AU Wu, Y
Chen, S
Zhang, M
Liu, K
Jing, J
Pan, K
Zhang, L
Xu, B
Lu, X
Chen, M
AF Wu, Yuqing
Chen, Saisai
Zhang, Minhao
Liu, Kuangzheng
Jing, Jibo
Pan, Kehao
Zhang, Lihua
Xu, Bin
Lu, Xiaoming
Chen, Ming
TI Factors Associated with Survival From Xp11.2 Translocation Renal Cell Carcinoma Diagnosis—A Systematic Review and Pooled Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE TFE3; kidney; Xp112 translocation renal cell carcinoma; survival; prognosis
ID TFE3; kidney; Xp112 translocation renal cell carcinoma; survival; prognosis
AB Purpose: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients. Methods: Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model. Results: There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; p = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; p = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; p < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; p = 0.027) were all associated with OS, with a median follow-up time of 198 months. Conclusion: T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.
C1 [Wu, Yuqing] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Chen, Saisai] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Zhang, Minhao] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Liu, Kuangzheng] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Jing, Jibo] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Pan, Kehao] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Zhang, Lihua] Affiliated Zhongda Hospital of Southeast University, Department of PathologyNanjing, China.
[Xu, Bin] Southeast University, School of Medicine, Surgical Research Center, Institute of UrologyNanjing, China.
[Lu, Xiaoming] Yancheng Third People's Hospital, Department of UrologyYancheng, China.
[Chen, Ming] Affiliated Zhongda Hospital of Southeast University, Department of UrologyNanjing, China.
RP Chen, M (reprint author), Affiliated Zhongda Hospital of Southeast University, Department of Urology, Nanjing, China.
EM mingchenseu@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 610360
EP 610368
DI 10.3389/pore.2021.610360
PG 9
ER
PT J
AU Mokanszki, A
Badon, SE
Monus, A
Toth, L
Bittner, N
Mehes, G
AF Mokanszki, Attila
Badon, Sarolta Emese
Monus, Aniko
Toth, Laszlo
Bittner, Nora
Mehes, Gabor
TI Cell-free DNA From Pleural Effusion Samples: Is It Right for Molecular Testing in Lung Adenocarcinoma?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung carcinoma; pleural effusion fluid; liquid biopsy; cytological cell block; mutation analysis
ID lung carcinoma; pleural effusion fluid; liquid biopsy; cytological cell block; mutation analysis
AB Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cellfree DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasmamutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.
C1 [Mokanszki, Attila] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Badon, Sarolta Emese] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Monus, Aniko] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Toth, Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Bittner, Nora] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
RP Mokanszki, A (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, Debrecen, Hungary.
EM mokanszki.attila@med.unideb.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 613071
EP 613077
DI 10.3389/pore.2021.613071
PG 7
ER
PT J
AU Dastych, M
Hubatka, F
Turanek-Knotigova, P
Masek, J
Kroupa, R
Raska, M
Turanek, J
Prochazka, L
AF Dastych, Milan
Hubatka, Frantisek
Turanek-Knotigova, Pavlina
Masek, Josef
Kroupa, Radek
Raska, Milan
Turanek, Jaroslav
Prochazka, Lubomir
TI Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD44 isoforms; colorectal precancerosis; colon polyps; cancer markers; RNA splicing
ID CD44 isoforms; colorectal precancerosis; colon polyps; cancer markers; RNA splicing
AB Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.
C1 [Dastych, Milan] University Hospital Brno and Faculty of Medicine Masaryk University Brno, Department of Gastroenterology and Internal MedicineBrno, Czech Republic.
[Hubatka, Frantisek] Veterinary Research Institute, Department of Pharmacology and ToxicologyBrno, Czech Republic.
[Turanek-Knotigova, Pavlina] Veterinary Research Institute, Department of Pharmacology and ToxicologyBrno, Czech Republic.
[Masek, Josef] Veterinary Research Institute, Department of Pharmacology and ToxicologyBrno, Czech Republic.
[Kroupa, Radek] University Hospital Brno and Faculty of Medicine Masaryk University Brno, Department of Gastroenterology and Internal MedicineBrno, Czech Republic.
[Raska, Milan] Palacky University Olomouc and the University Hospital Olomouc, Faculty of Medicine and Dentistry, Department of ImmunologyOlomouc, Czech Republic.
[Turanek, Jaroslav] Veterinary Research Institute, Department of Pharmacology and ToxicologyBrno, Czech Republic.
[Prochazka, Lubomir] Veterinary Research Institute, Department of Pharmacology and ToxicologyBrno, Czech Republic.
RP Turanek, J (reprint author), Veterinary Research Institute, Department of Pharmacology and Toxicology, Brno, Czech Republic.
EM turanek@seznam.cz
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 614281
EP 614291
DI 10.3389/pore.2021.614281
PG 11
ER
PT J
AU Simon, Zs
Virga, B
Pinczes, L
Mehes, G
Miltenyi, Zs
Barna, S
Szabo, R
Illes,
AF Simon, Zsofia
Virga, Balint
Pinczes, Laszlo
Mehes, Gabor
Miltenyi, Zsofia
Barna, Sandor
Szabo, Roxana
Illes, Arpad
TI Transition Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma– Our Histopathological and Clinical Experience With Patients With Intermediate Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gray zone lymphoma; hodgkin lymphoma; diffuse large B cell lymphoma; brentuximab vedotine; stem cell transplant
ID gray zone lymphoma; hodgkin lymphoma; diffuse large B cell lymphoma; brentuximab vedotine; stem cell transplant
AB Even though information about the pathophysiology and clinical features of grey-zone lymphoma, an entity intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma, is growing, there are still a number of unanswered questions. The disease has no easily reproducible diagnostic criteria, which makes identification challenging. Uncommon, mixed histological picture and unusual clinical presentation should raise suspicion for grey-zone lymphoma. In this retrospective analysis we present 9 gray zone lymphoma patients, who were diagnosed in our institute between 2008 and 2018. The histological diagnoses was oftentime challenging, we asked for a revision in three cases due to the unusual clinical behavior and in other three cases only the relapse of the disease proved to be grey-zone lymphoma. Based on the initial histopathological diagnoses we applied adriablastine-bleomycine-vinblastine and procarbasine or cyclophosphamide-vincristine-adriablastine and prednisolon as first line chemotherapy regime with additional rituximab in six cases and brentuximabvedotine in one patient. In six of the nine patients due to the primary refractory disease we used rituximab plus cisplatine, cytosine-arabinoside, prednisolone salvage treatment and five of these patients responded well enough to become eligible for autologous stem cell transplantation. One young male patient was refractory for various treatments and died due to the progression of his lymphoma. As a rare disease grey-zone lymphoma has no existing diagnostic criteria or guiedlines for its standard of care, which makes the everyday practice rather challenging for the clinicians, and emphasize the importance of unique decision making in every case and the repeated consultation between the pathologist and hematologist.
C1 [Simon, Zsofia] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Virga, Balint] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Pinczes, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Miltenyi, Zsofia] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Barna, Sandor] Scanomed Orvosi Diagnosztikai Kutato es Oktato Kft.Budapest, Hungary.
[Szabo, Roxana] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Illes, (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM illesarpaddr@gmail.com
CR Traverse-Glehen A, Pittaluga S, Gaulard P, Sorbara L, Alonso MA, Raffeld M, et al. Mediastinal gray zone lymphoma. Am J Surg Pathol, 2005). 29:1411–21., DOI 10.1097/01.pas.0000180856.74572.73
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Evens AM, Kanakry JA, Sehn LH, Kritharis A, Feldman T, Kroll A, et al. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort. Am J Hematol, 2015). 90: 778–83., DOI 10.1002/ajh.24082
Kritharis A, Pilichowska M, Evens AM How I manage patients with grey zone lymphoma. Br J Haematol, 2016). 174:345–50., DOI 10.1111/bjh.14174
Sarkozy C, Molina T, Ghesquieres H,Michallet A-S, Dupuis J, Damotte D, et al. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association. Haematologica, 2017). 102(1):150–9., DOI 10.3324/haematol. 2016.152256
Pilichowska M, Kritharis A, Evens AM Gray zone lymphoma. Hematology/ Oncology Clin North America, 2016). 30(6):1251–60., DOI 10.1016/j.hoc.2016.
.006 7. Mallipudi RM, Alqzran L, Shenoy VA, Leslie LA, Conti JA A rare case of grey zone lymphoma successfully treated with brentuximab vedotin and R-CHP chemotherapy. Case Rep Oncol Med, 2019). 1–4., DOI 10.1155/2019/ 4121234
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Svoboda J, Landsburg DJ, Nasta SD, et al. Brentuximab vedotin with R-CHP chemotherapy as frontline treatment for patients with Cd30 positive primary mediastinal large B-cell, diffuse large B-cell, and grey zone lymphomas: results of a phase I/II multisite trial. Blood, 2017). 130(Suppl. 1):191., DOI 10.3324/ haematol.2019.238675
Berger GK, McBride A, LAwson S, Royball K, Yun S, Gee K, et al. Brentuximab vedotin for treatment of non-Hodgkin lymphomas: a systematic review. Crit Rev Oncology/Hematology, 2017). 109:42–50., DOI 10.1016/j.critrevonc.2016.
009 11. Takaishi K, Muto T, Mimura N, Takiguchi J, Nagao Y, Oshima-Hasegawa N, et al. Long-term complete remission following tandem autologous stem cell transplantation and consolidative radiotherapy for refractory mediastinal gray-zone lymphoma. Int J Hematol, 2018). 108:452–5., DOI 10.1007/s12185- 018-2471-x
Melani C, Major A, Schowinsky J, Roschewski M, Pittaluga S, Jaffe ES, et al. PD-1 blockade in mediastinal gray-zone lymphoma. N Engl J Med, 2017). 377(1):89–91., DOI 10.1056/nejmc1704767
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 625529
EP 625535
DI 10.3389/pore.2021.625529
PG 7
ER
PT J
AU Mu, W
Su, P
Ning, Sh
AF Mu, Wentao
Su, Peng
Ning, Shanglei
TI Case Report: Incidentally Discovered a Rare Cystic Lesion of Liver: Multicystic Biliary Hamartoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE multicystic biliary hamartoma; cystic lesion of liver; laparoscopic resection; liver; immunohistochemistry
ID multicystic biliary hamartoma; cystic lesion of liver; laparoscopic resection; liver; immunohistochemistry
AB Multicystic biliary hamartoma (MCBH) is an extremely rare cystic lesion of the liver. A 37-year old male patient was admitted to our hospital for incidentally discovered hepatic cystic lesions on abdominal ultrasonography. Abdominal contrast-enhanced computed tomography (CT) showed a multilocular cystic lesion in the segment VI, with mild enhancement in the septae and peripheral wall within the lesion. Only alanine transaminase (ALT) and carbohydrate antigen 19–9 (CA19–9) increased slightly above normal value. Preoperative tests suggested possibility of a benign mucinous cystic neoplasm (MCN) or intraductal papillary neoplasm of the bile duct (IPNB). Laparoscopic complete resection of the lesion was performed. Histopathological examination showed numerous variably sized ductal structures surrounded by periductal glands and fibrous connective tissues containing small blood vessels and smooth muscle bundles. Immunohistochemical staining (IHC) revealed that dilated ducts were positive for cytokeratin CK19, characteristic for biliary tract. Histopathological findings confirmed diagnosis of multicystic biliary hamartoma (MCBH). No recurrence occurred during 6 months follow-up. In conclusion, MCBH should be differentiating from hepatic cystic lesion and could be resected laparoscopically safely.
C1 [Mu, Wentao] Qilu Hospital of Shandong University, Department of Hepatobiliary Surgery, General SurgeryJinan, China.
[Su, Peng] Shandong University, Qilu Hospital, Department of PathologyJinan, China.
[Ning, Shanglei] Qilu Hospital of Shandong University, Department of Hepatobiliary Surgery, General SurgeryJinan, China.
RP Ning, Sh (reprint author), Qilu Hospital of Shandong University, Department of Hepatobiliary Surgery, General Surgery, Jinan, China.
EM shangleining@163.com
CR Beard R. E., Yee E. U., Mortele K. J., Khwaja K., 2014). Multicystic biliary hamartoma: A report of a rare entity and a review of the literature. Int. J. Surg. Case Rep. 5, 12), 919–923., DOI 10.1016/j.ijscr.2014.10.014 Fernandez-Carrion M. J., Robles Campos R., Lopez Conesa A., Brusadin R., Parrilla Paricio P., 2015). Intrahepatic multicystic biliary hamartoma: Presentation of a case report. Cir. Esp. 93, 9), e103-5., DOI 10.1016/j.ciresp. 2014.02.015 Caroli J., Soupault R., Kossakowski J., Plocker L., Paradowska, 1958). Congenital polycystic dilation of the intrahepatic bile ducts; attempt at classification. Sem. Hop. 34, 8/2), 488–495. Heinke T, Pellacani L. B., Costa H. d. O., Fuziy R. A., Franco M., 2008). Hepatocellular carcinoma in association with bile duct hamartomas: report on 2 cases and review of the literature. Ann. Diagn. Pathol. 12, 3), 208–211., DOI 10.1016/j.anndiagpath.2006.12.003 Kai K., Takahashi T., Miyoshi A., Yasui T., Tokunaga O., Miyazaki K., 2008). Intrahepatic multicystic biliary hamartoma: report of a case. Hepatol. Res. 38, 6), 629–634., DOI 10.1111/j.1872-034x.2007.00314.x Kobayashi A., Takahashi S., Hasebe T, Konishi M, Nakagohri T, Gotohda N, et al., 2005). Solitary bile duct hamartoma of the liver. Scand. J. Gastroenterol. 40, 11), 1378–1381., DOI 10.1080/00365520510023387 Morinaga T., Imai K., Yamashita Y.-I., Yamao T., Kaida T.,Nakagawa S., et al., 2017). Multicystic biliary hamartoma with extremely elevated CA19-9: a case report. Scand. J. Gastroenterol. 52, 8), 916–919., DOI 10.1080/00365521.2017.1322140 Ogura T., Kurisu Y., Miyano A., Higuchi K., 2018). A huge rapidly-enlarging multicystic biliary hamartoma. Dig. Liver Dis. 50, 7), 723. Pitchaimuthu M., Duxbury M., 2017). Cystic lesions of the liver-A review. Curr. Probl. Surg. 54, 10), 514–542., DOI 10.1067/j.cpsurg.2017.09.001 Ryu Y., Matsui O., Zen Y., Ueda K., Abo H., Nakanuma Y., et al., 2010). Multicystic biliary hamartoma: imaging findings in four cases. Abdom Imaging 35, 5), 543–547., DOI 10.1007/s00261-009-9566-z Shi Q. S., Xing L. X., Jin L. F., Wang H., Lv X. H., Du L. F., et al., 2015). Imaging findings of bile duct hamartomas: a case report and literature review. Int. J. Clin. Exp. Med. 8, 8), 13145–13153. Song J. S., NohS. J., ChoB.H.,MoonW. S., 2013).Multicystic biliary hamartoma of the liver. Korean J. Pathol. 47, 3), 275–278., DOI 10.4132/koreanjpathol. 2013.47.3.275 Stocker J. T., Ishak K. G., 1983). Mesenchymal hamartoma of the liver: report of 30 cases and review of the literature. Pediatr. Pathol. 1, 3), 245–267., DOI 10.3109/ 15513818309040663 Sugawara T., Shindoh J., Hoshi D., Hashimoto M., 2018). Intrahepatic cholangiocarcinoma and portal hypertension developing in a patient with multicystic biliary microhamartomas. Malays. J. Pathol. 40, 3), 331–335. Tominaga T., Abo T., KinoshitaN.,Murakami T., Sato Y.,Nakanuma Y., et al., 2015). A variant of multicystic biliary hamartoma presenting as an intrahepatic cystic neoplasm. Clin. J. Gastroenterol. 8, 3), 162–166., DOI 10.1007/s12328-015-0574-y Yoh T., Okamura R., Nakayama H., Lin X., Nakamura Y., Kato T., 2014). Multicystic biliary hamartoma mimicking intrahepatic cholangiocarcinoma: Report of a case. Clin. J. Gastroenterol. 7, 5), 418–421., DOI 10.1007/s12328-014-0513-3 Zen Y., Terahata S., Miyayama S., Mitsui T., Takehara A., Miura S., et al., 2006). Multicystic biliary hamartoma. Hum. Pathol. 37, 3), 339–344., DOI 10.1016/j. humpath.2005.11.008
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 628323
EP 628327
DI 10.3389/pore.2021.628323
PG 5
ER
PT J
AU Deng, Y
Zhao, Y
Qin, J
Huang, X
Wu, R
Zhou, C
Pan, Z
AF Deng, Yuxiang
Zhao, Yujie
Qin, Jiayi
Huang, Xiaozhen
Wu, Ruomei
Zhou, Caixia
Pan, Zhizhong
TI Prognostic Value of the C-Reactive Protein/Albumin Ratio and Systemic Immune-Inflammation Index for Patients With Colorectal Liver Metastasis Undergoing Curative Resection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal neoplasms; liver metastases; prognosis; CAR; SII
ID colorectal neoplasms; liver metastases; prognosis; CAR; SII
AB Background: We evaluated the prognostic value of C-reactive protein/albumin (CAR) and systemic immune-inflammation index (SII), which we calculated as neutrophil × platelet/ lymphocyte) in patients with colorectal liver metastasis (CRLM) after curative resection. Methods: We retrospectively enrolled 283 consecutive patients with CRLM who underwent curative resection between 2006 and 2016. We determined the optimal cutoff values of CAR and SII using receiver operating curve (ROC) analysis. Overall survival (OS)- and recurrence-free survival (RFS)-related to CAR and SII were analyzed using the log-rank test and multivariate Cox regression methods. Results: We found that a high CAR was significantly associated with poor OS (P < 0.001) and RFS (P = 0.008) rates compared with a low CAR; a high SII was significantly associated with poor RFS (P = 0.003) rates compared with a low SII. The multivariate analysis indicated that CAR was an independent predictor of OS (hazard ratio [HR] = 2.220; 95% confidence interval [CI] = 1.387–3.550; P = 0.001) and RFS (HR = 1.494; 95% CI = 1.086–2.056; P = 0.014). The SII was an independent predictor of RFS (HR = 1.973; 95% CI = 1.230–3.162; P = 0.005) in patients with CRLM. Conclusion: We proved that CAR was an independent predictor of OS and RFS in patients with CRLM who underwent curative resection, and that the prognostic value of CAR was superior to that of SII.
C1 [Deng, Yuxiang] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Zhao, Yujie] Peking University Shenzhen Hospital, Department of Radiation OncologyShenzhen, China.
[Qin, Jiayi] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Huang, Xiaozhen] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Wu, Ruomei] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Zhou, Caixia] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Pan, Zhizhong] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
RP Pan, Z (reprint author), Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal Surgery, Guangzhou, China.
EM panzhzh@sysucc.org.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 633480
EP 633489
DI 10.3389/pore.2021.633480
PG 10
ER
PT J
AU Stockhammer, P
Okumus,
Hegedus, L
Rittler, D
Ploenes, T
Herold, Th
Kalbourtzis, S
Bankfalvi,
Sucker, A
Kimmig, R
Aigner, C
Hegedus, B
AF Stockhammer, Paul
Okumus, Ozlem
Hegedus, Luca
Rittler, Dominika
Ploenes, Till
Herold, Thomas
Kalbourtzis, Stavros
Bankfalvi, Agnes
Sucker, Antje
Kimmig, Rainer
Aigner, Clemens
Hegedus, Balazs
TI HDAC Inhibition Induces Cell Cycle Arrest and Mesenchymal-Epithelial Transition in a Novel Pleural-Effusion Derived Uterine Carcinosarcoma Cell Line
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE uterine carcinosarcoma; targeted therapy; HDAC inhibition; epithelial-mesenchymal transition; mesenchymal-epithelial transition; ARID1A
ID uterine carcinosarcoma; targeted therapy; HDAC inhibition; epithelial-mesenchymal transition; mesenchymal-epithelial transition; ARID1A
AB Objective: Uterine carcinosarcoma (UCS) is a rare but highly aggressive malignancy with biphasic growth pattern. This morphology can be attributed to epithelial-mesenchymal transition (EMT) that often associates with tumor invasion and metastasis. Accordingly, we analyzed a novel patient-derived preclinical model to explore whether EMT is a potential target in UCS. Methods: A novel UCS cell line (PF338) was established from the malignant pleural effusion of a 59-year-old patient at time of disease progression. Immunohistochemistry was performed in primary and metastatic tumor lesions. Oncogenic mutations were identified by next-generation sequencing. Viability assays and cell cycle analyses were used to test in vitro sensitivity to different standard and novel treatments. E-cadherin, β-catenin and pSMAD2 expressions were measured by immunoblot. Results: Whereas immunohistochemistry of the metastatic tumor showed a predominantly sarcomatous vimentin positive tumor that has lost E-cadherin expression, PF338 cells demonstrated biphasic growth and carried mutations in KRAS, PIK3CA, PTEN and ARID1A. PF338 tumor cells were resistant to MEK- and TGF-β signaling-inhibition but sensitive to PIK3CA- and PARP-inhibition and first-line chemotherapeutics. Strikingly, histone deacetylase (HDAC) inhibition markedly reduced cell viability by inducing a dose-dependent G0/1 arrest and led to mesenchymal-epithelial transition as evidenced by morphological change and increased E-cadherin and β-catenin expression. Conclusions: Our data suggest that HDAC inhibition is effective in a novel UCS cell line by interfering with both viability and differentiation. These findings emphasize the dynamic manner of EMT/MET and epigenetics and the importance of molecular profiling to pave the way for novel therapies in UCS.
C1 [Stockhammer, Paul] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Okumus, Ozlem] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Luca] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Rittler, Dominika] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Ploenes, Till] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Herold, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Kalbourtzis, Stavros] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Bankfalvi, Agnes] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Sucker, Antje] University Duisburg-Essen, University Hospital Essen, Department of DermatologyEssen, Germany.
[Kimmig, Rainer] University Duisburg-Essen, University Hospital Essen, Department of Gynecology and ObstetricsEssen, Germany.
[Aigner, Clemens] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Balazs] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
RP Hegedus, B (reprint author), University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic Surgery, Essen, Germany.
EM balazs.hegedues@rlk.uk-essen.de
CR Silverberg SG, Major FJ, Blessing JA, Fetter B, Askin FB, Liao S-Y, et al. Carcinosarcoma, malignant mixed mesodermal tumor, of the uterus. Int J Gynecol Pathol, 1990). 9(1):1–19., DOI 10.1097/00004347-199001000-00001
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2021
VL 27
IS 1
BP 636088
EP 636097
DI 10.3389/pore.2021.636088
PG 10
ER
PT J
AU Ma, J
Du, R
Huang, Y
Zhong, W
Gui, H
Mao, Ch
Song, X
Lu, J
AF Ma, Jin
Du, Rao
Huang, Yan
Zhong, Wen
Gui, Huan
Mao, Chenmei
Song, Xiudao
Lu, Jun
TI Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE non-small cell lung cancer; NFATs; prognosis; bioinformatics analysis; gene expression
ID non-small cell lung cancer; NFATs; prognosis; bioinformatics analysis; gene expression
AB Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.
C1 [Ma, Jin] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Du, Rao] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Huang, Yan] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Zhong, Wen] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Gui, Huan] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Mao, Chenmei] Children’s Hospital of Soochow University, Department of PharmacySuzhou, China.
[Song, Xiudao] Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Clinical Pharmaceutical Laboratory of Traditional Chinese MedicineSuzhou, China.
[Lu, Jun] Children’s Hospital of Soochow University, Department of HaematologySuzhou, China.
RP Song, X (reprint author), Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Clinical Pharmaceutical Laboratory of Traditional Chinese Medicine, Suzhou, China.
EM songxiudao0109@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 529240
EP 529256
DI 10.3389/pore.2021.529240
PG 17
ER
PT J
AU Shen, W
Shan, B
Liang, Sh
Zhang, J
Yu, Y
Zhang, Y
Wang, G
Bai, Y
Qian, B
Lu, J
Jiang, Z
AF Shen, Wenbin
Shan, Boer
Liang, Shanhui
Zhang, Junling
Yu, Yangyang
Zhang, Yuzi
Wang, Guoqiang
Bai, Yuezong
Qian, Bing
Lu, Jin
Jiang, Zhi
TI Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE circulating tumor DNA; liquid biopsy; ovarian cancer; genomic profiling; genomic alterations
ID circulating tumor DNA; liquid biopsy; ovarian cancer; genomic profiling; genomic alterations
AB Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases. Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N=488) and the Cancer Genome Atlas (TCGA) database (N=489). Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05). Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.
C1 [Shen, Wenbin] Fudan University Shanghai Cancer Center, Department of OncologyShanghai, China.
[Shan, Boer] Fudan University Shanghai Cancer Center, Department of OncologyShanghai, China.
[Liang, Shanhui] Fudan University Shanghai Cancer Center, Department of OncologyShanghai, China.
[Zhang, Junling] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Yu, Yangyang] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhang, Yuzi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Wang, Guoqiang] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Bai, Yuezong] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Qian, Bing] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical University, Departments of Gynecomatous SurgeryNanjing, China.
[Lu, Jin] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical University, Departments of Gynecomatous SurgeryNanjing, China.
[Jiang, Zhi] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical University, Departments of Gynecomatous SurgeryNanjing, China.
RP Jiang, Z (reprint author), Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical University, Departments of Gynecomatous Surgery, Nanjing, China.
EM margrate71@163.com
CR Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY Ovarian cancer. Nat Rev Dis Primers, 2016). 2:16061., DOI 10.1038/nrdp.2016.61
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: ovarian cancer, version 1.2020). Available from: https://www.nccn. org/professionals/physician_gls/default.aspx.
Kondrashova O, Nguyen M, Shield-Artin K, Tinker AV, Teng NNH, Harrell MI, et al. Secondary somaticmutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov, 2017). 7(9):984–98., DOI 10.1158/2159-8290.cd-17-0419
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 581534
EP 581539
DI 10.3389/pore.2021.581534
PG 6
ER
PT J
AU Zheng, L
Kang, L
Cheng, Y
Cao, J
Liu, L
Xu, H
Gao, L
AF Zheng, Lei
Kang, Liying
Cheng, Yan
Cao, Junli
Liu, Lijie
Xu, Hongmei
Gao, Liming
TI Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE long non-coding RNA LOC100505817; wnt/β-catenin signaling pathway; gastric cancer; epithelialmesenchymal transition; proliferation; invasion; migration; apoptosis
ID long non-coding RNA LOC100505817; wnt/β-catenin signaling pathway; gastric cancer; epithelialmesenchymal transition; proliferation; invasion; migration; apoptosis
AB Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/β-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained fromGC patients, expression of LOC100505817, Wnt/β-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, β-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/ β-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/ β-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.
C1 [Zheng, Lei] The First Hospital of Qinhuangdao, Department of OncologyQinhuangdao, China.
[Kang, Liying] Wuqing People Hospital, Department of OncologyTianjin, China.
[Cheng, Yan] The First Hospital of Qinhuangdao, Disinfection Supply RoomQinhuangdao, China.
[Cao, Junli] The First Hospital of Qinhuangdao, Department of OncologyQinhuangdao, China.
[Liu, Lijie] The First Hospital of Qinhuangdao, Department of OncologyQinhuangdao, China.
[Xu, Hongmei] The First Hospital of Qinhuangdao, Department of OncologyQinhuangdao, China.
[Gao, Liming] The First Hospital of Qinhuangdao, Department of OncologyQinhuangdao, China.
RP Gao, L (reprint author), The First Hospital of Qinhuangdao, Department of Oncology, Qinhuangdao, China.
EM tshgaoliming@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 581542
EP 581553
DI 10.3389/pore.2021.581542
PG 12
ER
PT J
AU Zhang, D
Dai, J
Pan, Y
Wang, X
Qiao, J
Sasano, H
Zhao, B
McNamara, K
Guan, X
Liu, L
Zhang, Y
Chan, M
Cao, Sh
Liu, M
Song, S
Wang, L
AF Zhang, Dongmei
Dai, Jiali
Pan, Yu
Wang, Xiuli
Qiao, Juanjuan
Sasano, Hironobu
Zhao, Baoshan
McNamara, M. Keely
Guan, Xue
Liu, Lili
Zhang, Yanzhi
Chan, S. M. Monica
Cao, Shuwen
Liu, Ming
Song, Sihang
Wang, Lin
TI Overexpression of PELP1 in Lung Adenocarcinoma Promoted E2 Induced Proliferation, Migration and Invasion of the Tumor Cells and Predicted a Worse Outcome of the Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE estrogen; proline-; glutamic acid-; leucine-rich protein 1; lung adenocarcinoma; tumor progression
ID estrogen; proline-; glutamic acid-; leucine-rich protein 1; lung adenocarcinoma; tumor progression
AB The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients. We then performed in vitro analysis including MTT, flow cytometry, wound healing, and transwell assays in order to further explore the biological roles of PELP1 in 17-β-estradiol (E2) induced cell proliferation, migration, and invasion of LUAD cells. We subsequently evaluated the prognostic significance of PELP1 in LUAD patients using the online survival analysis tool Kaplan-Meier Plotter. The status of PELP1 immunoreactivity in LUAD was significantly higher than that in the NTL tissues and significantly positively correlated with less differentiated features of carcinoma cells, positive lymph node metastasis, higher clinical stage as well as the status of ERα, ERβ, and PCNA. In vitro study did reveal that E2 promoted cell proliferation and migration and elevated PELP1 protein level in PELP1-high A549 and H1975 cells but not in PELP1-low H-1299 cells. Knock down of PELP1 significantly attenuated E2 induced cell proliferation, colony formation, cell cycle progress as well as migration and invasion of A549 and H1975 cells. Kaplan-Meier Plotter revealed that LUAD cases harboring higher PELP1 expression had significantly shorter overall survival. In summary, PELP1 played a pivotal role in the estrogen-induced aggressive transformation of LUAD and could represent adverse clinical outcome of the LUAD patients.
C1 [Zhang, Dongmei] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Dai, Jiali] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Pan, Yu] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Wang, Xiuli] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Qiao, Juanjuan] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Sasano, Hironobu] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Zhao, Baoshan] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[McNamara, M. Keely] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Guan, Xue] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Liu, Lili] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Zhang, Yanzhi] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Chan, S. M. Monica] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Cao, Shuwen] Daqing Oilfield General Hospital, Department of PathologyDaqing, China.
[Liu, Ming] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Song, Sihang] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
[Wang, Lin] Harbin Medical University-Daqing, Department of PathologyDaqing, China.
RP Wang, L (reprint author), Harbin Medical University-Daqing, Department of Pathology, Daqing, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 582443
EP 582453
DI 10.3389/pore.2021.582443
PG 11
ER
PT J
AU Yang, X
Miao, S
Mao, X
Xiu, Ch
Sun, J
Pei, R
Jia, Sh
AF Yang, Xianguang
Miao, Susheng
Mao, Xionghui
Xiu, Cheng
Sun, Ji
Pei, Rong
Jia, Shenshan
TI LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE laryngeal squamous cell carcinoma; ZEB1; migration; invasion; EZH2; LINC-PINT
ID laryngeal squamous cell carcinoma; ZEB1; migration; invasion; EZH2; LINC-PINT
AB Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment. Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened. Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition. Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.
C1 [Yang, Xianguang] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Miao, Susheng] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Mao, Xionghui] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Xiu, Cheng] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Sun, Ji] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Pei, Rong] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
[Jia, Shenshan] Harbin Medical University Cancer Hospital, Department of Head and Neck SurgeryHarbin, China.
RP Jia, Sh (reprint author), Harbin Medical University Cancer Hospital, Department of Head and Neck Surgery, Harbin, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 584466
EP 584476
DI 10.3389/pore.2021.584466
PG 11
ER
PT J
AU Aslam, N
Abusharieh, E
Abuarqoub, D
Alhattab, D
Jafar, H
Alshaer, W
Masad, R
Awidi, A
AF Aslam, Nazneen
Abusharieh, Elham
Abuarqoub, Duaa
Alhattab, Dana
Jafar, Hanan
Alshaer, Walhan
Masad, J. Razan
Awidi, S. Abdalla
TI An In Vitro Comparison of Anti-Tumoral Potential of Wharton’s Jelly and Bone Marrow Mesenchymal Stem Cells Exhibited by Cell Cycle Arrest in Glioma Cells (U87MG)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mesenchymal stem cells; glioblastoma; secretome; WJ-MSCs; BM-MSC; cell lysate MSC-condition media
ID mesenchymal stem cells; glioblastoma; secretome; WJ-MSCs; BM-MSC; cell lysate MSC-condition media
AB The therapeutic potential ofmesenchymal stem cells (MSCs) for variousmalignancies is currently under investigation due to their unique properties. However,many discrepancies regarding their anti-tumoral or pro-tumoral properties have raised uncertainty about their application for anticancer therapies. To investigate, if the anti-tumoral or pro-tumoral properties are subjective to the type of MSCs under different experimental conditions we set out these experiments. Three treatments namely cell lysates (CL), serum-free conditioned media and FBS conditioned media (FBSCM) from each of Wharton’s Jelly MSCs and BoneMarrow-MSCs were applied to evaluate the anti-tumoral or pro-tumoral effect on the glioma cells (U87MG). The functional analysis included; Morphological evaluation, proliferation and migration potential, cell cycle analysis, and apoptosis for glioma cells. The fibroblast cell line was added to investigate the stimulatory or inhibitory effect of treatments on the proliferation of the normal cell. We found that cell lysates induced a generalized inhibitory effect on the proliferation of the glioma cells and the fibroblasts from both types of MSCs. Similarly, both types of conditioned media from two types of MSCs exerted the same inhibitory effect on the proliferation of the glioma cells. However, the effect of two types of conditioned media on the proliferation of fibroblasts was stimulatory from BMMSCs and variable from WJ-MSCs. Moreover, all three treatments exerted a likewise inhibitory effect on themigration potential of the glioma cells. Furthermore,we found that the cell cycle was arrested significantly at the G1 phase after treating cells with conditionedmedia whichmay have led to inhibit the proliferative and migratory abilities of the glioma cells (U87MG).We conclude that cell extracts of MSCs in the form of secretome can induce specific anti-tumoral properties in serum-free conditions for the glioma cells particularly theWJ-MSCs and the effect is mediated by the cell cycle arrest at the G1 phase.
C1 [Aslam, Nazneen] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Abusharieh, Elham] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Abuarqoub, Duaa] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Alhattab, Dana] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Jafar, Hanan] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Alshaer, Walhan] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Masad, J. Razan] The University of Jordan, Cell Therapy CenterAmman, Jordan.
[Awidi, S. Abdalla] The University of Jordan, Cell Therapy CenterAmman, Jordan.
RP Awidi, A (reprint author), The University of Jordan, Cell Therapy Center, Amman, Jordan.
EM aabbadi@ju.edu.jo
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 584710
EP 584726
DI 10.3389/pore.2021.584710
PG 17
ER
PT J
AU Choi, IS
AF Choi, Il Sun
TI Effects of Gallotannin-Enriched Extract of Galla Rhois on the Activation of Apoptosis, Cell Cycle Arrest, and Inhibition of Migration Ability in LLC1 Cells and LLC1 Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE galla rhois; gallotanin; apoptosis; migration; NF-kB signaling pathway; lung carcinoma
ID galla rhois; gallotanin; apoptosis; migration; NF-kB signaling pathway; lung carcinoma
AB Gallotannin (GT) and GT-enriched extracts derived from various sources are reported to have anti-tumor activity in esophageal, colon and prostate tumors, although their antitumor effects have not been determined in lung carcinomas. To investigate the anti-tumor activity of GT-enriched extract of galla rhois (GEGR) against lung carcinomas, alterations in the cytotoxicity, apoptosis activation, cell cycle progression, migration ability, tumor growth, histopathological structure, and the regulation of signaling pathways were analyzed in Lewis lung carcinoma (LLC1) cells and LLC1 tumor bearing C57BL/6NKorl mice, after exposure to GEGR. A high concentration of GT (69%) and DPPH scavenging activity (IC50=7.922 μg/ml) was obtained in GEGR. GEGR treatment exerted strong cytotoxicity, cell cycle arrest at the G2/M phase and subsequent activation of apoptosis, as well as inhibitory effects on the MAPK pathway and PI3K/AKT mediated cell migration in LLC1 cells. In the in vivo syngeneic model, exposure to GEGR resulted in suppressed growth of the LLC1 tumors, as well as inhibition of NF-κB signaling and their inflammatory cytokines. Taken together, our results provide novel evidence that exposure to GEGR induces activation of apoptosis, cell cycle arrest, and inhibition of cell migration via suppression of the MAPK, NF-κB and PI3K/AKT signaling pathways in LLC1 cells and the LLC1 syngeneic model.
C1 [Choi, Il Sun] Research Institute of National Cancer Center, Goyang, Division of Convergence TechnologyGoyang, South Korea.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 588084
EP 588101
DI 10.3389/pore.2021.588084
PG 18
ER
PT J
AU Sato, N
Ise, K
Hata, Sh
Yamashita, Sh
Ito, A
Sasano, H
Nakamura, Y
AF Sato, Naomi
Ise, Kazue
Hata, Shuko
Yamashita, Shinichi
Ito, Akihiro
Sasano, Hironobu
Nakamura, Yasuhiro
TI Clinicopathological Significance of Estrogen Receptor β and Estrogen Synthesizing/Metabolizing Enzymes in Urothelial Carcinoma of Urinary Bladder
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ERβ; urothelial bladder carcinoma; steroid metabolism; steroid sulfatase; aromatase; estrogen sulfotransferase 5
ID ERβ; urothelial bladder carcinoma; steroid metabolism; steroid sulfatase; aromatase; estrogen sulfotransferase 5
AB Sex-specific differences in the incidence of urinary bladder carcinomas are well known, and the possible involvement of sex steroids has been proposed. We previously reported the association of the loss of androgen receptors and androgen-producing enzymes with tumor progression of urinary bladder cancer patients. Clinically, the selective estrogen receptor modulators (SERMs) were reported to suppress the progression of these tumors but the status of estrogen receptors (ERs) has not been well studied in patients with bladder urinary cancer. Moreover, not only ERs but also estrogen-related enzymes, such as aromatase, steroid sulfatase (STS), and estrogen sulfotransferase (EST), have been reported in the biological/clinical behavior of various hormone-dependent carcinomas but not studied in urinary bladder carcinoma. Therefore, in this study, we immunolocalized ERs as well as estrogen metabolizing enzymes in urinary bladder carcinoma and performed immunoblotting and cell proliferation assays using the bladder urothelial carcinoma cell line, T24. The results revealed that the loss of STS and aromatase was significantly correlated with advanced stages of the carcinoma. In vitro studies also revealed that T24 cell proliferation rates were significantly ameliorated after treatment with estradiol or diarylpropionitrile (DPN). EST and aromatase were also significantly correlated with the nuclear grade of the carcinoma. The results of our present study, for the first time, demonstrated that biologically active estrogens that bind to ERs could suppress tumor progression and the inactive ones could promote its progression and the potential clinical utility of SERM treatment in selective patients with urinary bladder carcinoma.
C1 [Sato, Naomi] Sendai City Hospital, Division of PathologySendai, Japan.
[Ise, Kazue] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Hata, Shuko] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Yamashita, Shinichi] Tohoku University Graduate School of Medicine, Department of UrologySendai, Japan.
[Ito, Akihiro] Tohoku University Graduate School of Medicine, Department of UrologySendai, Japan.
[Sasano, Hironobu] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
[Nakamura, Yasuhiro] Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of PathologySendai, Japan.
RP Nakamura, Y (reprint author), Tohoku Medical and Pharmaceutical University, Faculty of Medicine, Division of Pathology, Sendai, Japan.
EM yasu-naka@tohoku-mpu.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 589649
EP 589655
DI 10.3389/pore.2021.589649
PG 7
ER
PT J
AU Yuan, W
Yan, J
Liu, H
Li, L
Wu, B
Guo, C
Zhang, M
AF Yuan, Wei
Yan, Jiaqin
Liu, Hongtao
Li, Ling
Wu, BoWen
Guo, Can
Zhang, Mingzhi
TI Identification of Prognostic Related Genes of Tumor Microenvironment Derived From Esophageal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal cancer; ESTIMATE score; stromal score; immune score; the tumor microenvironment
ID Esophageal cancer; ESTIMATE score; stromal score; immune score; the tumor microenvironment
AB Background and Objective: Esophageal cancer (ESCA) is a commonly occurring cancer worldwide with poor survival and limited therapeutic options. Due to the lack of biomarkers that facilitate early detection, its treatment remains a great challenge. This study aims at identifying the tumor microenvironment (TME)-related genes, which might affect prognosis and accelerate clinical treatment for ESCA patients. Methods: We integrated the expression profiles from ESCA patients in The Cancer Genome Atlas. Then, we determined the stromal and immune scores of each sample using the R package. The Gene Expression Omnibus database was used to validate the expression profile of the key genes. Results: Tumor mutational burden showed a significant difference between the groups of ESCA patients with high and low ESTIMATE scores. We identified 859 intersection genes among patients with different immune and stromal scores. Moreover, gene ontology analysis demonstrated that these 859 intersection genes were closely related to adaptive immune response and regulation of lymphocyte activation. Kyoto Encyclopedia of Genes and Genomes showed the enrichment of cytokine-cytokine receptor interaction and chemokine signaling pathway in the TME. Furthermore, the protein–protein interaction network consisted of 175 nodes. We selected 35 hub genes, including ITGAM, CXCL10, CCR2, CCR5, and CCR1. Of these, 23 intersection genes predicted the overall survival rate. C1QA and FCER1G correlated with overall survival of the ESCA patients in the two databases. Conclusion: We identified a set of stromal and immune score-related prognostic differentially expressed genes that could influence the complexity of the TME. C1QA and FCER1G were identified and validated with respect to their role in the progression of ESCA.
C1 [Yuan, Wei] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
[Yan, Jiaqin] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
[Liu, Hongtao] Zhengzhou University, College of Life SciencesZhengzhou, China.
[Li, Ling] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
[Wu, BoWen] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
[Guo, Can] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
[Zhang, Mingzhi] First Affiliated Hospital of Zhengzhou University, Department of OncologyZhengzhou, China.
RP Zhang, M (reprint author), First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, China.
EM mingzhi_zhang1@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 589662
EP 589672
DI 10.3389/pore.2021.589662
PG 11
ER
PT J
AU Zhang, X
Zhang, J
Liu, Y
Li, J
Tan, J
Song, Z
AF Zhang, Xi
Zhang, Junjun
Liu, Yang
Li, Jie
Tan, Juan
Song, Zewen
TI Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE BAG2; hepatocellar carcinoma; ribosome biogenesis; invasion; apoptosis
ID BAG2; hepatocellar carcinoma; ribosome biogenesis; invasion; apoptosis
AB Background: Bcl-2 associated athanogene2 (BAG2) is reported to act as an oncogene or a tumor-suppressor in tumors in a context-dependent way; however, its function in hepatocellular carcinoma (HCC) remains unclear. Methods: Immunohistochemistry (IHC) staining, cell counting kit-8 (CCK-8) assay, apoptotic assay, cell invasion assay and a set of bioinformatics tools were integrated to analyze the role of BAG2 in hepatocellular carcinoma. Results: BAG2 was significantly up-regulated in HCC. Prognostic analysis indicated that HCC patients with high expression of BAG2 had significantly shorter overall survival, progression free survival and disease specific survival. Besides, silencing BAG2 in HCC cells impaired cell proliferation, facilitated apoptosis and repressed invasion of the cells. Bioinformatics analysis showed that BAG2 might regulate ribosome biogenesis in HCC. Conclusion: This study revealed that the up-regulated BAG2 in HCC was associated with a worse prognosis and might favor the progression of the disease.
C1 [Zhang, Xi] The Third Xiangya Hospital of Central South University, Department of OncologyChangsha, China.
[Zhang, Junjun] The Third Xiangya Hospital of Central South University, Department of OncologyChangsha, China.
[Liu, Yang] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, China.
[Li, Jie] Hunan University of Chinese Medicine, Department of Information Science and EngineeringChangsha, China.
[Tan, Juan] Central South University, Third Xiangya Hospital, Department of PathologyChangsha, China.
[Song, Zewen] The Third Xiangya Hospital of Central South University, Department of OncologyChangsha, China.
RP Song, Z (reprint author), The Third Xiangya Hospital of Central South University, Department of Oncology, Changsha, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 594649
EP 594661
DI 10.3389/pore.2021.594649
PG 13
ER
PT J
AU Du, H
Luo, F
Shi, M
Che, J
Zhu, L
Li, H
Hang, J
AF Du, Hailei
Luo, Fangxiu
Shi, Minmin
Che, Jiaming
Zhu, Lianggang
Li, Hecheng
Hang, Junbiao
TI Beclin-1 is a Promising Prognostic Biomarker in a Specific Esophageal Squamous Cell Carcinoma Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE esophageal squamous cell carcinoma (ESCC); autophagy; apoptosis; beclin-1; Prognosis
ID esophageal squamous cell carcinoma (ESCC); autophagy; apoptosis; beclin-1; Prognosis
AB The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues (p < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern (p < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant (p > 0.05), whereas Beclin-1 expression was significantly associated with OS (p < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.
C1 [Du, Hailei] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic SurgeryShanghai, China.
[Luo, Fangxiu] Shanghai Jiao Tong University School ofMedicine, Ruijin Hospital North, Department of PathologyShanghai, China.
[Shi, Minmin] Institute of Digestive SurgeryShanghai, China.
[Che, Jiaming] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic SurgeryShanghai, China.
[Zhu, Lianggang] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic SurgeryShanghai, China.
[Li, Hecheng] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic SurgeryShanghai, China.
[Hang, Junbiao] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic SurgeryShanghai, China.
RP Hang, J (reprint author), Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Thoracic Surgery, Shanghai, China.
EM drhangjb@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 594724
EP 594732
DI 10.3389/pore.2021.594724
PG 9
ER
PT J
AU Meder, Ly
Florin, A
Ozretic, L
Nill, M
Koker, M
Meemboor, S
Radtke, F
Diehl, L
Ullrich, R
Odenthal, M
Buttner, R
Heukamp, L
AF Meder, Lydia
Florin, Alexandra
Ozretic, Luka
Nill, Marieke
Koker, Mirjam
Meemboor, Sonja
Radtke, Freddy
Diehl, Linda
Ullrich, T. Roland
Odenthal, Margarete
Buttner, Reinhard
Heukamp, C. Lukas
TI Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an Autochthonous KrasLSL-G12V Driven Lung Cancer Mouse Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mouse model; lung cancer; KRAS; NOTCH1; TAZ
ID mouse model; lung cancer; KRAS; NOTCH1; TAZ
AB Purpose: Abrogation of Notch signaling, which is pivotal for lung development and pulmonary epithelial cell fate decisions was shown to be involved in the aggressiveness and the differentiation of lung carcinomas. Additionally, the transcription factors YAP and TAZ which are involved in the Hippo pathway, were recently shown to be tightly linked with Notch signaling and to regulate the cell fate in epidermal stem cells. Thus, we aim to elucidate the effects of conditional Notch1 deficiency on carcinogenesis and TAZ expression in lung cancer. Methods: We investigated the effect of conditional Cre-recombinase mediated Notch1 knock-out on lung cancer cells in vivo using an autochthonous mouse model of lung adenocarcinomas driven by KrasLSL-G12V and comprehensive immunohistochemical analysis. In addition, we analyzed clinical samples and human lung cancer cell lines for TAZ expression and supported our findings by publicly available data from The Cancer Genome Atlas (TCGA). Results: In mice, we found induction of papillary adenocarcinomas and protrusions of tumor cells from the bronchiolar lining upon Notch1 deficiency. Moreover, the mutated Kras driven lung tumors with deleted Notch1 showed increased TAZ expression and focal nuclear translocation which was frequently observed in human pulmonary adenocarcinomas and squamous cell carcinomas of the lung, but not in small cell lung carcinomas. In addition, we used data from TCGA to show that putative inactivating NOTCH1 mutations co-occur with KRAS mutations and genomic amplifications in lung adenocarcinomas. Conclusion: Our in vivo study provides evidence that Notch1 deficiency in mutated Kras driven lung carcinomas contributes to lung carcinogenesis in a subgroup of patients by increasing TAZ expression who might benefit from TAZ signaling blockade.
C1 [Meder, Lydia] University Hospital Cologne, Department I of Internal MedicineCologne, Germany.
[Florin, Alexandra] University of Cologne Medical School, Institute of PathologyCologne, Germany.
[Ozretic, Luka] Royal Free Hospital, Department of Cellular PathologyLondon, UK.
[Nill, Marieke] University Hospital Cologne, Department I of Internal MedicineCologne, Germany.
[Koker, Mirjam] University Hospital Cologne, Department I of Internal MedicineCologne, Germany.
[Meemboor, Sonja] University of Cologne Medical School, Institute of PathologyCologne, Germany.
[Radtke, Freddy] Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Federale de LausanneLausanne, Switzerland.
[Diehl, Linda] University Medical Center Hamburg-Eppendorf, Institute of Experimental Immunology and HepatologyHamburg, Germany.
[Ullrich, T. Roland] University Hospital Cologne, Department I of Internal MedicineCologne, Germany.
[Odenthal, Margarete] University of Cologne, Center for Molecular Medicine CologneCologne, Germany.
[Buttner, Reinhard] University of Cologne, Center for Molecular Medicine CologneCologne, Germany.
[Heukamp, C. Lukas] Institute for Hematopathology HamburgHamburg, Germany.
RP Meder, Ly (reprint author), University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany.
EM lydia.meder@uk-koeln.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 596522
EP 596533
DI 10.3389/pore.2021.596522
PG 12
ER
PT J
AU Cruz-Rico, G
Aviles-Salas, A
Popa-Navarro, X
Lara-Mejia, L
Catalan, R
Sanchez-Reyes, R
Lopez-Sanchez, D
Cabrera-Miranda, L
Maldonado-Martinez, AH
Samtani-Bassarmal, S
Arrieta, O
AF Cruz-Rico, Graciela
Aviles-Salas, Alejandro
Popa-Navarro, Xitlally
Lara-Mejia, Luis
Catalan, Rodrigo
Sanchez-Reyes, Roberto
Lopez-Sanchez, Dennis
Cabrera-Miranda, Luis
Maldonado-Martinez, Aquiles Hector
Samtani-Bassarmal, Suraj
Arrieta, Oscar
TI Association of Lung Adenocarcinoma Subtypes According to the IASLC/ ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; NSCLC; lung adenocarcinoma; programmed-death receptor ligand 1 (PD-L1); immunohistochemistry; Tumor-infiltrating lymphocytes (TILs) 4
ID immunotherapy; NSCLC; lung adenocarcinoma; programmed-death receptor ligand 1 (PD-L1); immunohistochemistry; Tumor-infiltrating lymphocytes (TILs) 4
AB Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features. Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival. Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23–94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PDL1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominantpapillary pattern, and 68.7% of patients with predominant-solid pattern (p 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS. Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.
C1 [Cruz-Rico, Graciela] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Aviles-Salas, Alejandro] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Popa-Navarro, Xitlally] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Lara-Mejia, Luis] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Catalan, Rodrigo] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Sanchez-Reyes, Roberto] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Lopez-Sanchez, Dennis] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Cabrera-Miranda, Luis] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Maldonado-Martinez, Aquiles Hector] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
[Samtani-Bassarmal, Suraj] Clinica Bradford Hill, Medical Oncology ServiceSantiago, Chile.
[Arrieta, Oscar] Instituto Nacional de Cancerologia, Thoracic Oncology UnitMexico City, Mexico.
RP Arrieta, O (reprint author), Instituto Nacional de Cancerologia, Thoracic Oncology Unit, Mexico City, Mexico.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 597499
EP 597507
DI 10.3389/pore.2021.597499
PG 9
ER
PT J
AU Zhang, R
Huang, M
Wang, H
Wu, Sh
Yao, J
Ge, Y
Lu, Y
Hu, Q
AF Zhang, Ruohao
Huang, Miao
Wang, Hong
Wu, Shengming
Yao, Jiali
Ge, Yingying
Lu, Yufei
Hu, Qiping
TI Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hepatocellular carcinoma; copy number variation; metallothionein; hub gene; deletion; screening; biomarker
ID hepatocellular carcinoma; copy number variation; metallothionein; hub gene; deletion; screening; biomarker
AB Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC. Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis. Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion. Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.
C1 [Zhang, Ruohao] Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and GeneticsNanning, China.
[Huang, Miao] Affiliated Tumor Hospital of Guangxi Medical University, Radiology DepartmentNanning, China.
[Wang, Hong] Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and GeneticsNanning, China.
[Wu, Shengming] Affiliated Tumor Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Yao, Jiali] Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and GeneticsNanning, China.
[Ge, Yingying] Guangxi Medical University, School of Pre-clinical Medicine, Department of Histology and EmbryologyNanning, China.
[Lu, Yufei] Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and GeneticsNanning, China.
[Hu, Qiping] Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and GeneticsNanning, China.
RP Hu, Q (reprint author), Guangxi Medical University, School of Pre-clinical Medicine, Department of Cell Biology and Genetics, Nanning, China.
EM huqiping@gxmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 597527
EP 597539
DI 10.3389/pore.2021.597527
PG 13
ER
PT J
AU Tamasi, L
Horvath, K
Kiss, Z
Bogos, K
Ostoros, Gy
Muller, V
Urban, L
Bittner, N
Sarosi, V
Vastag, A
Polanyi, Z
Nagy-Erdei, Zs
Daniel, A
Nagy, B
Rokszin, Gy
Abonyi-Toth, Zs
Moldvay, J
Voko, Z
Galffy, G
AF Tamasi, Lilla
Horvath, Krisztian
Kiss, Zoltan
Bogos, Krisztina
Ostoros, Gyula
Muller, Veronika
Urban, Laszlo
Bittner, Nora
Sarosi, Veronika
Vastag, Aladar
Polanyi, Zoltan
Nagy-Erdei, Zsofia
Daniel, Andrea
Nagy, Balazs
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Moldvay, Judit
Voko, Zoltan
Galffy, Gabriella
TI Age and Gender Specific Lung Cancer Incidence and Mortality in Hungary: Trends from 2011 Through 2016
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epidemiology; lung cancer; incidence; mortality; age and gender
ID epidemiology; lung cancer; incidence; mortality; age and gender
AB Objective: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between January 1, 2011 and December 31, 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any cancer treatment other than lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increased with age, peaking in the 70–79 age group (375.0/100,000 person-years) among males, while at 60–69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46–3.01 (p < 0.0001) among the 70–79 age group. We found 2–11% decrease in male incidence rate at most age groups, while a significant 1–3% increase was observed in older females (>60) annually during the study period. Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary decreased in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.
C1 [Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Horvath, Krisztian] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Kiss, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute for TB and Pulmonology, Department of PulmonologyBudapest, Hungary.
[Ostoros, Gyula] National Koranyi Institute for TB and Pulmonology, Department of PulmonologyBudapest, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Urban, Laszlo] Matrahaza Healthcare Center and University Teaching HospitalMatrahaza, Hungary.
[Bittner, Nora] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of MedicinePecs, Hungary.
[Vastag, Aladar] MSD Pharma Hungary Kft.Budapest, Hungary.
[Polanyi, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy-Erdei, Zsofia] MSD Pharma Hungary Kft.Budapest, Hungary.
[Daniel, Andrea] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy, Balazs] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Department of Tumor BiologyBudapest, Hungary.
[Voko, Zoltan] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Galffy, Gabriella] Semmelweis University, Department of PulmonologyBudapest, Hungary.
RP Horvath, K (reprint author), Eotvos Lorand University, Department of Health Policy and Health Economics, Budapest, Hungary.
EM horvath.krisztian@tatk.elte.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 598862
EP 598870
DI 10.3389/pore.2021.598862
PG 9
ER
PT J
AU Peng, L
Zhang, Z
Zhao, D
Zhao, J
Mao, F
Sun, Q
AF Peng, Li
Zhang, Zhen
Zhao, Dachun
Zhao, Jialin
Mao, Feng
Sun, Qiang
TI Discordance in ER, PR, HER2, and Ki-67 Expression Between Primary and Recurrent/Metastatic Lesions in Patients with Primary Early Stage Breast Cancer and the Clinical Significance: Retrospective Analysis of 75 Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomolecular status; discordance; recurrence; metastatic disease; PFS; breast cancer; surrogate subtypes
ID biomolecular status; discordance; recurrence; metastatic disease; PFS; breast cancer; surrogate subtypes
AB Background: The objective was to explore the discordance in the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 between primary and recurrent/metastatic lesions in patients with early stage breast cancer as well as the prognostic impact. Method: Patients with early-stage primary breast cancer and confirmed recurrence/ metastasis at Peking Union Medical College Hospital between January 2005 and August 2018 were screened. The details of discordance in each parameter between primary and recurrent/metastatic lesions and progression were recorded. Regression and survival analysis were applied to determine the association and clinical impact of the discordance. Results: We evaluated 75 patients. The discordance rate of ER, PR, HER2, and Ki-67 expression was 9.3, 14.7, 14.7, and 21.5%, respectively. Additionally, 66.7, 11.8, 14.3, and 0% of patients with Luminal A, Luminal B, HER2, and triple-negative primary tumors presented with a different subtype for the recurrent/metastatic tumors, respectively. No statistical difference in progression-free survival was observed according to the subtype of the recurrent or metastatic breast cancer (p > 0.05). Among 69 patients for whom treatment was adjusted after recurrence or metastasis, 66 patients remained recurrence-free during the follow-up period. Conclusion: For patients with early-stage breast cancer, the ER, PR, HER2, and Ki-67 expression profile for recurrent/metastatic tumors does not always match that of the primary tumor. After adjusting treatment according to the receptor expression in recurrent/ metastatic lesions, most patients remained progression-free during the follow-up period.
C1 [Peng, Li] Peking Union Medical College Hospital, Department of Breast SurgeryBeijing, China.
[Zhang, Zhen] Peking Union Medical College Hospital, Department of Breast SurgeryBeijing, China.
[Zhao, Dachun] Peking Union Medical College Hospital, Department of PathologyBeijing, China.
[Zhao, Jialin] Peking Union Medical College Hospital, Department of Breast SurgeryBeijing, China.
[Mao, Feng] Peking Union Medical College Hospital, Department of Breast SurgeryBeijing, China.
[Sun, Qiang] Peking Union Medical College Hospital, Department of Breast SurgeryBeijing, China.
RP Mao, F (reprint author), Peking Union Medical College Hospital, Department of Breast Surgery, Beijing, China.
EM mmc8941@me.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 599894
EP 599906
DI 10.3389/pore.2021.599894
PG 13
ER
PT J
AU Hakim, AS
Gabal, HAH
AF Hakim, Adel Sarah
Gabal, Hassan Abou Hoda
TI Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mesothelioma; reactive mesothelial hyperplasia; BAP1; EZH2; survivin; immunohistochemistry
ID mesothelioma; reactive mesothelial hyperplasia; BAP1; EZH2; survivin; immunohistochemistry
AB Background: Epithelioid mesothelioma (EM) is the commonest subtype of malignant pleural mesothelioma. Its histopathological discrimination from reactive mesothelial hyperplasia (RMH) could be challenging. Thus, an immunohistochemical panel is mandatory for better discrimination. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. EZH2 overexpression is reported in different cancers, but its relation to BAP1 in malignant mesothelioma has not been fully understood. Survivin expression is said to be significantly higher in EM than in nonneoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field. To the best of our knowledge, no previous studies have been conducted to assess the diagnostic accuracy of the combined use of these three nuclear markers (BAP1, EZH2 and Survivin) in discriminating pleural EM from RMH. Methods: This retrospective study includes two groups: 81 cases of pleural EM and 67 cases of RMH, retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from January 2016 to December 2019. An immunohistochemical study was performed using BAP1, EZH2 and Survivin antibodies. Results: There were highly statistically significant relations between study groups as regards the studied markers (p = 0.001 for each). The specificity was 100% for all combinations of immunohistochemical markers. Sensitivity of any combination of the immunohistochemical markers used in this study was found to be higher than the sensitivity of any of these markers used individually. The combination of all three markers showed the highest diagnostic accuracy (95.9%) and the highest sensitivity (92.6%). However, the combination of Survivin and EZH2 yielded the same diagnostic accuracy and sensitivity. Conclusion: Adding EZH2, Survivin and BAP1 to the diagnostic IHC panel for differentiating pleural EM and RMH could enhance diagnostic sensitivity. Moreover, Survivin is a potentially promising marker in this context, especially when combined with EZH2.
C1 [Hakim, Adel Sarah] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
[Gabal, Hassan Abou Hoda] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
RP Hakim, AS (reprint author), Ain Shams Faculty of Medicine, Department of Pathology, Cairo, Egypt.
EM sarahadel2003@yahoo.com
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Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. Lung Cancer, 2019). 130:187–93., DOI 10.1016/j.lungcan.2019.02.004 16. Kushitani K, Amatya VJ, Mawas AS, Suzuki R, Miyata Y, Okada M., et al. Utility of survivin, BAP1, and ki-67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia. Oncol Lett, 2018). 15:3540–7., DOI 10.3892/ol.2018.7765 17. Rossini M, Rizzo P, Bononi I, Clementz A, Ferrari R, Martini F., et al. New perspectives on diagnosis and therapy of malignant pleural mesothelioma. Front Oncol, 2018). 8:91., DOI 10.3389/fonc.2018.00091 18. Hida T, HamasakiM,Matsumoto S, Sato A, Tsujimura T, Kawahara K., et al. BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests. 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Low merlin expression and high survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma. Mol Oncol, 2016). 10(8):1255–65., DOI 10.1016/j.molonc.2016.06.005 23. Hmeljak J, Erˇculj N, Dolˇzan V, Piˇzem J, Kern I, Kovaˇc V., et al. Is survivin expression prognostic or predictive in malignant pleural mesothelioma? Virchows Arch, 2013). 462(3):315–21., DOI 10.1007/s00428-013-1373-9 24. Bilecz A, Stockhammer P, Theegarten D, Kern I, Jakopovic M, Samarzija M., et al. Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma. Histopathology, 2020). 77(1): 55–66., DOI 10.1111/his.14105 25. Chapel DB, Husain AN, Krausz T. Immunohistochemical evaluation of nuclear 5-hydroxymethylcytosine, 5-hmC, accurately distinguishes malignant pleural mesothelioma from benign mesothelial proliferations. Mod Pathol, 2019). 32(3):376–86., DOI 10.1038/s41379-018-0159-7 26. 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Immunohistochemical expression and serum level of survivin protein in colorectal cancer patients. Oncol Lett, 2016). 12:3591–7., DOI 10. 3892/ol.2016.5075
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 600073
EP 600082
DI 10.3389/pore.2021.600073
PG 10
ER
PT J
AU Qi, A
Ju, M
Liu, Y
Bi, J
Wei, Q
He, M
Wei, M
Zhao, L
AF Qi, Aoshuang
Ju, Mingyi
Liu, Yinfeng
Bi, Jia
Wei, Qian
He, Miao
Wei, Minjie
Zhao, Lin
TI Development of a Novel Prognostic Signature Based on Antigen Processing and Presentation in Patients with Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE antigen processing and presentation; breast cancer; cell biology; prognostic; survival
ID antigen processing and presentation; breast cancer; cell biology; prognostic; survival
AB Background: Complex antigen processing and presentation processes are involved in the development and progression of breast cancer (BC). A single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer; however, there have been few attempts to find a robust antigen processing and presentation-related signature to predict the survival outcome of BC patients with respect to tumor immunology. Therefore, we aimed to develop an accurate gene signature based on immune-related genes for prognosis prediction of BC. Methods: Information on BC patients was obtained from The Cancer Genome Atlas. Gene set enrichment analysis was used to confirm the gene set related to antigen processing and presentation that contributed to BC. Cox proportional regression, multivariate Cox regression, and stratified analysis were used to identify the prognostic power of the gene signature. Differentially expressed mRNAs between high- and low-risk groups were determined by KEGG analysis. Results: A three-gene signature comprising HSPA5 (heat shock protein family A member 5), PSME2 (proteasome activator subunit 2), and HLA-F (major histocompatibility complex, class I, F) was significantly associated with OS. HSPA5 and PSME2 were protective (hazard ratio (HR) < 1), and HLA-F was risky (HR > 1). Risk score, estrogen receptor (ER), progesterone receptor (PR) and PD-L1 were independent prognostic indicators. KIT and ACACB may have important roles in the mechanismby which the gene signature regulates prognosis of BC. Conclusion: The proposed three-gene signature is a promising biomarker for estimating survival outcomes in BC patients.
C1 [Qi, Aoshuang] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Ju, Mingyi] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Liu, Yinfeng] The First Hospital of Qinhuangdao, Department of Breast SurgeryQinhuangdao, China.
[Bi, Jia] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Wei, Qian] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[He, Miao] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Wei, Minjie] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
[Zhao, Lin] China Medical University, School of Pharmacy, Department of PharmacologyShenyang, China.
RP Zhao, L (reprint author), China Medical University, School of Pharmacy, Department of Pharmacology, Shenyang, China.
EM lzhao@cmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 600727
EP 600737
DI 10.3389/pore.2021.600727
PG 11
ER
PT J
AU Zhou, W
Chen, Y
Luo, R
Li, Z
Jiang, G
Ou, X
AF Zhou, Wanbang
Chen, Yiyang
Luo, Ruixing
Li, Zifan
Jiang, Guanwei
Ou, Xi
TI Identification of Biomarkers Related to Immune Cell Infiltration in Hepatocellular Carcinoma Using Gene Co-Expression Network
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hepatocellular carcinoma; CIBERSORT; weighted gene co-expression network analysis; bioinformatics; the cancer genome atlas
ID hepatocellular carcinoma; CIBERSORT; weighted gene co-expression network analysis; bioinformatics; the cancer genome atlas
AB Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment.Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.
C1 [Zhou, Wanbang] Peking University Shenzhen HospitalShenzhen, China.
[Chen, Yiyang] Peking University Shenzhen HospitalShenzhen, China.
[Luo, Ruixing] Peking University Shenzhen HospitalShenzhen, China.
[Li, Zifan] Peking University Shenzhen HospitalShenzhen, China.
[Jiang, Guanwei] Peking University Shenzhen HospitalShenzhen, China.
[Ou, Xi] Peking University Shenzhen HospitalShenzhen, China.
RP Ou, X (reprint author), Peking University Shenzhen Hospital, Shenzhen, China.
EM bdszyyox@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 601693
EP 601704
DI 10.3389/pore.2021.601693
PG 12
ER
PT J
AU Yuan, J
Kihara, T
Kimura, N
Hashikura, Y
Ohkouchi, M
Isozaki, K
Takahashi, T
Nishida, T
Ito, A
Hirota, S
AF Yuan, Jiayin
Kihara, Takako
Kimura, Neinei
Hashikura, Yuka
Ohkouchi, Mizuka
Isozaki, Koji
Takahashi, Tsuyoshi
Nishida, Toshirou
Ito, Akihiko
Hirota, Seiichi
TI Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastrointestinal stromal tumor; GIST; CADM1; gastric GIST; duodenal/jejuno-ileal GIST; mutation type
ID gastrointestinal stromal tumor; GIST; CADM1; gastric GIST; duodenal/jejuno-ileal GIST; mutation type
AB Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.
C1 [Yuan, Jiayin] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Kihara, Takako] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Kimura, Neinei] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Hashikura, Yuka] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Ohkouchi, Mizuka] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Isozaki, Koji] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
[Takahashi, Tsuyoshi] Osaka University Graduate School of Medicine, Departtment of Gastroenterological SurgerySuita, Japan.
[Nishida, Toshirou] Osaka Hospital, Japan Community Healthcare Organization (JCHO)Osaka, Japan.
[Ito, Akihiko] Kindai University, Faculty of Medicine, Department of PathologyOsaka, Japan.
[Hirota, Seiichi] Hyogo College of Medicine, Department of Surgical PathologyNishinomiya, Japan.
RP Hirota, S (reprint author), Hyogo College of Medicine, Department of Surgical Pathology, Nishinomiya, Japan.
EM hiros@hyo-med.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 602008
EP 602017
DI 10.3389/pore.2021.602008
PG 10
ER
PT J
AU Mao, L
Zhao, W
Li, X
Zhang, Sh
Zhou, Ch
Zhou, D
Ou, X
Xu, Y
Tang, Y
Ou, X
Hu, Ch
Ding, X
Luo, P
Yu, Sh
AF Mao, Linlin
Zhao, Weiwei
Li, Xiaoxia
Zhang, Shangfei
Zhou, Changhong
Zhou, Danyan
Ou, Xiaohua
Xu, Yanyan
Tang, Yuanxiao
Ou, Xiaoyong
Hu, Changming
Ding, Xiangdong
Luo, Pifu
Yu, Shihui
TI Mutation Spectrum of EGFR From 21,324 Chinese Patients With Non-Small Cell Lung Cancer (NSCLC) Successfully Tested by Multiple Methods in a CAP-Accredited Laboratory
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE non-small cell lung cancer; EGFR mutation testing; Sanger sequencing; real-time PCR; next-generation sequencing
ID non-small cell lung cancer; EGFR mutation testing; Sanger sequencing; real-time PCR; next-generation sequencing
AB Genotyping epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancers (NSCLC) is essential for identifying those patients who may benefit from targeted therapies. Systemically evaluating EGFR mutation detection rates of different methods currently used in clinical setting will provide valuable information to clinicians and laboratory scientists who take care of NSCLC patients. This study retrospectively reviewed the EGFR data obtained in our laboratory in last 10 years. A total of 21,324 NSCLC cases successfully underwent EGFR genotyping for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next-generation sequencing (NGS). The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Of these cases with EGFR mutations identified, 93.3% of them harbored a single EGFR mutation (92.1% with 19del or L858R, and 7.9% with uncommon mutations) and 6.7% harbored complex EGFR mutations. Of the 72 distinct EGFR variants identified in this study, 15 of them (single or complex EGFR mutations) were newly identified in NSCLC. For these cases with EGFR mutations tested by NGS, 65.3% of them also carried tumor-related variants in some non-EGFR genes and about one third of them were considered candidates of targeted drugs. NGS method showed advantages over Sanger sequencing and real-time PCR not only by providing the highest mutation detection rate of EGFR but also by identifying actionable non-EGFR mutations with targeted drugs in clinical setting.
C1 [Mao, Linlin] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Zhao, Weiwei] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Li, Xiaoxia] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Zhang, Shangfei] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Zhou, Changhong] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Zhou, Danyan] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Ou, Xiaohua] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Xu, Yanyan] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Tang, Yuanxiao] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Ou, Xiaoyong] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Hu, Changming] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
[Ding, Xiangdong] KingMed Diagnostics, Department of PathologyGuangzhou, China.
[Luo, Pifu] KingMed Diagnostics, Department of PathologyGuangzhou, China.
[Yu, Shihui] KingMed Diagnostics, Clinical Genome CenterGuangzhou, China.
RP Yu, Sh (reprint author), KingMed Diagnostics, Clinical Genome Center, Guangzhou, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 602726
EP 602733
DI 10.3389/pore.2021.602726
PG 8
ER
PT J
AU Bogos, K
Kiss, Z
Tamasi, L
Ostoros, Gy
Muller, V
Urban, L
Bittner, N
Sarosi, V
Vastag, A
Polanyi, Z
Nagy-Erdei, Zs
Daniel, A
Voko, Z
Nagy, B
Horvath, K
Rokszin, Gy
Abonyi-Toth, Zs
Barcza, Zs
Galffy, G
Moldvay, J
AF Bogos, Krisztina
Kiss, Zoltan
Tamasi, Lilla
Ostoros, Gyula
Muller, Veronika
Urban, Laszlo
Bittner, Nora
Sarosi, Veronika
Vastag, Aladar
Polanyi, Zoltan
Nagy-Erdei, Zsofia
Daniel, Andrea
Voko, Zoltan
Nagy, Balazs
Horvath, Krisztian
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Barcza, Zsofia
Galffy, Gabriella
Moldvay, Judit
TI Improvement in Lung Cancer Survival: 6-Year Trends of Overall Survival at Hungarian Patients Diagnosed in 2011–2016
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; long-term survival; mortality; Hungary; survival
ID lung cancer; long-term survival; mortality; Hungary; survival
AB Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients (n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75–0.79; p < 0.001) than males (n = 25,492). The highest survival rates were found in the 20–49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015–2016 to 2011–2012 (HR: 0.95 95% CI: 0.92–0.97; p = 0.003), the highest at females <60 year (0.86 (adjusted HR was 0.79), interaction analysis was significant for age and histology types. Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to–and at the higher end of–rates registered in other East-Central European countries (7.7%–15.7%).
C1 [Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Kiss, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Ostoros, Gyula] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Urban, Laszlo] Matrahaza Healthcare Center and University Teaching HospitalMatrahaza, Hungary.
[Bittner, Nora] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of MedicinePecs, Hungary.
[Vastag, Aladar] MSD Pharma Hungary Kft.Budapest, Hungary.
[Polanyi, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy-Erdei, Zsofia] MSD Pharma Hungary Kft.Budapest, Hungary.
[Daniel, Andrea] MSD Pharma Hungary Kft.Budapest, Hungary.
[Voko, Zoltan] Eotvos Lorand UniversityBudapest, Hungary.
[Nagy, Balazs] Eotvos Lorand UniversityBudapest, Hungary.
[Horvath, Krisztian] Eotvos Lorand UniversityBudapest, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Barcza, Zsofia] Syntesia LtdBudapest, Hungary.
[Galffy, Gabriella] County Hospital of PulmonologyTorokbalint, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Semmelweis University, Ist Department of PulmonologyBudapest, Hungary.
RP Bogos, K (reprint author), National Koranyi Institute of Pulmonology, Budapest, Hungary.
EM bogos@koranyi.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 603937
EP 603945
DI 10.3389/pore.2021.603937
PG 9
ER
PT J
TI Single Cell Gene Transcriptome Analysis of Ovarian Mature Teratomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE teratoma; expression profile; single cell; ovarian tumor; transcriptome
ID teratoma; expression profile; single cell; ovarian tumor; transcriptome
AB Teratoma is a type of germ cell tumor that originates from totipotential germ cells that are present in gonads, which can differentiate into any of the cell types found in adult tissues. Ovarian teratomas are usually mature cystic teratomas (OMCTs, also known as dermoid cysts). Chromosome studies in OMCTs show that the chromosomes are uniformly homozygous with karyotype of 46, XX, indicating that they may be parthenogenic tumors that arise from a single ovum after thefirst meiotic division. However, the tissues in OMCTs have been known to be morphologically and immunophenotypically identical to the orthotopic tissues. Currently, expression profiles of tissue components in OMCTs are not known. To identify whether OMCT tissues are expressionally similar to or different from the orthotopic tissues, we adopted single-cell RNA-sequencing (scRNAseq), and analyzed transcriptomes of individual cells in heterogenous tissues of two OMCTs. We found that transcriptome profiles of the OMCTs at single cell level were not significantly different from those of normal cells in orthotopic locations. The present data suggest that parthenogeneticlly altered OMCTs may not alter expression profiles of inrivirual tissue components in OMCTs.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 604228
EP 604232
DI 10.3389/pore.2021.604228
PG 5
ER
PT J
AU Zhou, W
Wang, Y
Gao, H
Jia, Y
Xu, Y
Wan, X
Zhang, Z
Yu, H
Yan, Sh
AF Zhou, Weiyu
Wang, Yujing
Gao, Hongmei
Jia, Ying
Xu, Yuanxin
Wan, Xiaojing
Zhang, Zhiying
Yu, Haiqiao
Yan, Shuang
TI Identification of Key Genes Involved in Pancreatic Ductal Adenocarcinoma with Diabetes Mellitus Based on Gene Expression Profiling Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE diabetes mellitus; pancreatic ductal adenocarcinoma; meta-analysis; support vector machine; survival analysis
ID diabetes mellitus; pancreatic ductal adenocarcinoma; meta-analysis; support vector machine; survival analysis
AB This study aimed to identify key genes involved in the progression of diabetic pancreatic ductal adenocarcinoma (PDAC). Two gene expression datasets (GSE74629 and GSE15932) were obtained from Gene Expression Omnibus. Then, differentially expressed genes (DEGs) between diabetic PDAC and non-diabetic PDAC were identified, followed by a functional analysis. Subsequently, gene modules related to DM were extracted by weighed gene co-expression network analysis. The protein-protein interaction (PPI) network for genes in significant modules was constructed and functional analyses were also performed. After that, the optimal feature genes were screened by support vector machine (SVM) recursive feature elimination and SVM classification model was built. Finally, survival analysis was conducted to identify prognostic genes. The correlations between prognostic genes and other clinical factors were also analyzed. Totally, 1546 DEGs with consistent change tendencies were identified and functional analyses showed they were strongly correlated with metabolic pathways. Furthermore, there were two significant gene modules, in which RPS27A and UBA52 were key genes. Functional analysis of genes in two gene modules revealed that these genes primarily participated in oxidative phosphorylation pathway. Additionally, 21 feature genes were closely related with diabetic PDAC and the corresponding SVM classifier markedly distinguished diabetic PDAC from non-diabetic PDAC patients. Finally, decreased KIF22 and PYGL levels had good survival outcomes for PDAC. Four genes (RPS27A, UBA52, KIF22 and PYGL) might be involved in the pathogenesis of diabetic PDAC. Furthermore, KIF22 and PYGL acted as prognostic biomarkers for diabetic PDAC.
C1 [Zhou, Weiyu] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Wang, Yujing] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Gao, Hongmei] The Fourth Affiliated Hospital of Harbin Medical University, Department of NeurologyHarbin, China.
[Jia, Ying] The First Affiliated Hospital of Harbin Medical University, Department of PathologyHarbin, China.
[Xu, Yuanxin] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Wan, Xiaojing] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Zhang, Zhiying] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Yu, Haiqiao] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
[Yan, Shuang] The Fourth Affiliated Hospital of Harbin Medical University, Department of EndocrinologyHarbin, China.
RP Yan, Sh (reprint author), The Fourth Affiliated Hospital of Harbin Medical University, Department of Endocrinology, Harbin, China.
EM qingmei0724@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 604730
EP 604739
DI 10.3389/pore.2021.604730
PG 10
ER
PT J
AU Moon, WS
Son, JH
Mo, YH
Yoo, JN
Lee, HS
AF Moon, Won Seong
Son, Ji Hyun
Mo, Yoon Ha
Yoo, Jin Nam
Lee, Hyung Sug
TI Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NLRP; Somatic mutation; loss of expression; cancer; colon cancer
ID NLRP; Somatic mutation; loss of expression; cancer; colon cancer
AB Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of NLRP1, NLRP2, NLRP4 and NLRP9, and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no NLRP frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the NLRP9 frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in NLRP9-mutated cases was significantly lower than that in NLRP9-non-mutated cases. Our data indicate that NLRP9 is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.
C1 [Moon, Won Seong] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Son, Ji Hyun] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Mo, Yoon Ha] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Yoo, Jin Nam] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
[Lee, Hyung Sug] The Catholic University of Korea, College of Medicine, Department of PathologySeoul, South Korea.
RP Lee, HS (reprint author), The Catholic University of Korea, College of Medicine, Department of Pathology, Seoul, South Korea.
EM suhulee@catholic.ac.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 607385
EP 607391
DI 10.3389/pore.2021.607385
PG 7
ER
PT J
AU Zhang, X
Zhang, H
Li, J
Ma, X
He, Z
Liu, C
Gao, Ch
Li, H
Wang, X
Wu, J
AF Zhang, Xiaoming
Zhang, Haiyan
Li, Jie
Ma, Xiaoran
He, Zhengguo
Liu, Cun
Gao, Chundi
Li, Huayao
Wang, Xue
Wu, Jibiao
TI 6-lncRNA Assessment Model for Monitoring and Prognosis of HER2-Positive Breast Cancer: Based on Transcriptome Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE human epidermal growth factor receptor 2-positive breast cancer; random forests; prognosis; long noncoding RNA; competing endogenous RNA
ID human epidermal growth factor receptor 2-positive breast cancer; random forests; prognosis; long noncoding RNA; competing endogenous RNA
AB Background: In view of the high malignancy and poor prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, we analyzed the RNA expression profiles of HER2-positive breast cancer samples to identify the new prognostic biomarkers. Methods: The linear fitting method was used to identify the differentially expressed RNAs from the HER2-positive breast cancer RNA expression profiles in the Cancer Genome Atlas (TCGA). Then, a series of methods including univariate Cox, Kaplan-Meier, and random forests, were used to identify the core long non-coding RNAs (lncRNAs) with stable prognostic value for HER2-positive breast cancer. A clinical feature analysis was performed, and a competing endogenous RNA network was constructed to explore the role of these core lncRNAs in HER2-positive breast cancer. In addition, a functional analysis of differentially expressed messenger RNAs in HER-2 positive breast cancer also provided us with some enlightening insights. Results: The high expression of four core lncRNAs (AC010595.1, AC046168.1, AC069277.1, and AP000904.1) was associated with worse overall survival, while the low expression of LINC00528 and MIR762HG was associated with worse overall survival. The 6-lncRNA model has an especially good predictive power for overall survival (p < 0.0001) and 3-year survival (the area under the curve = 0.980) in HER2-positive breast cancer patients. Conclusion: This study provides a new efficient prognostic model and biomarkers of HER2-positive breast cancer. Meanwhile, it also provides a new perspective for elucidating the molecular mechanisms underlying HER2-positive breast cancer.
C1 [Zhang, Xiaoming] Shandong University of Traditional Chinese Medicine, College of Chinese MedicineJinan, China.
[Zhang, Haiyan] Shandong University of Traditional Chinese Medicine, College of Chinese MedicineJinan, China.
[Li, Jie] Shandong University of Traditional Chinese Medicine, College of Chinese MedicineJinan, China.
[Ma, Xiaoran] Shandong University of Traditional Chinese Medicine, The First Clinical Medical CollegeJinan, China.
[He, Zhengguo] Columbus Technical CollegeColumbus, GA, USA.
[Liu, Cun] Shandong University of Traditional Chinese Medicine, The First Clinical Medical CollegeJinan, China.
[Gao, Chundi] Shandong University of Traditional Chinese Medicine, The First Clinical Medical CollegeJinan, China.
[Li, Huayao] Shandong University of Traditional Chinese Medicine, College of Chinese MedicineJinan, China.
[Wang, Xue] Qingdao University, College of Basic MedicineQingdao, China.
[Wu, Jibiao] Shandong University of Traditional Chinese Medicine, College of Chinese MedicineJinan, China.
RP Wu, J (reprint author), Shandong University of Traditional Chinese Medicine, College of Chinese Medicine, Jinan, China.
EM wujibiao1963@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 609083
EP 609095
DI 10.3389/pore.2021.609083
PG 13
ER
PT J
AU Behzatoglu, K
AF Behzatoglu, Kemal
TI Osteoclasts in Tumor Biology: Metastasis and Epithelial- Mesenchymal-Myeloid Transition
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE tumor biology; metastasis; breast carcinoma metastasis; giant cell tumor of bone; EMMT; osteoclast; epithelial-mesenchymal-myeloid transition
ID tumor biology; metastasis; breast carcinoma metastasis; giant cell tumor of bone; EMMT; osteoclast; epithelial-mesenchymal-myeloid transition
AB Osteoclast is a specialized cell that originates from monocytic lineage, communicates closely with osteoblasts under physiological conditions, participates in bone modeling and remodeling, contributes to calcium homeostasis and osteoimmunity. In pathological conditions, it is involved in many tumors such as giant cell bone tumor (osteoclastoma), aneurysmal bone cyst, osteosarcoma, and metastatic cancers, and it usually causes local spread and progression of the tumor, working against the host. Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-osteoclastic agents significantly reduces the mortality and morbidity rates of patients by preventing the progression and local spread of tumors. Osteoclasts also accompany undifferentiated carcinomas of many organs, especially pancreas, thyroid, bladder and ovary. Undifferentiated carcinomas rich in osteoclasts have osteoclastoma-like histology. In these organs, osteoclastoma-like histology may accompany epithelial carcinomas, and de novo, benign and borderline tumors. Mature and immature myeloid cells, including osteoclasts, play an active role in the tumor progression in primary and metastatic tumor microenvironment, in epithelial-mesenchymal transition (EMT), mesenchymal-epithelialtransition (MET), and cancer stem cell formation. Additionally, they are the most suitable candidates for cancer cells in cell fusion due to their evolutionary fusion capabilities. Myeloid features and markers (CD163, CD33, CD68 etc.) can be seen in metastatic cancer cells. Consequently, they provide metastatic cancer cells with motility, margination, transmigration, chemotaxis, phagocytosis, angiogenesis, matrix degradation, and resistance to chemotherapy. For these reasons, we think that the concept of Epithelial-Mesencyhmal-Myeloid-Transition (EMMT) will be more accurate than EMT for cancer cells with myeloid properties.
C1 [Behzatoglu, Kemal] Acibadem University, School of Medicine, Pathology DepartmentIstanbul, Turkey.
RP Behzatoglu, K (reprint author), Acibadem University, School of Medicine, Pathology Department, Istanbul, Turkey.
EM kbehzatoglu@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 609472
EP 609484
DI 10.3389/pore.2021.609472
PG 13
ER
PT J
AU Bus, D
Nagy, Gy
Poka, R
Vajda, Gy
AF Bus, Dorottya
Nagy, Gyongyi
Poka, Robert
Vajda, Gyorgy
TI Clinical Impact of Preoperative Magnetic Resonance Imaging in the Evaluation of Myometrial Infiltration and Lymph-Node Metastases in Stage I Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE endometrial; MRI; Cancer; Radical hysterectomy; postoperative stage; preoperative stage
ID endometrial; MRI; Cancer; Radical hysterectomy; postoperative stage; preoperative stage
AB Purpose: In the developed world, endometrial cancer is one of the most common malignant gynecological cancer types. Due to the highly available diagnostic modalities and patient education, the early detection of the tumor leads to high overall survival. Methods: In this study we analyzed the reliability of preoperativeMRI findings in the staging of early stage endometrial cancer, as well as the clinical characteristics of patients underwent radical hysterectomy and the histopathologic evaluation of their tumor, with the retrospective data of radical hysterectomies performed in our hospital between 2010 and 2019. Results: The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI regarding stage were 94.7, 63.3, 94.8, 83.8, and 83.8%, respectively. The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI for the detection of the myometrial invasion were 69.8, 80.0, 60.8, 64.3, and 77.5%, respectively. The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI for the detection of lymph node metastases were 78.1, 28.6, 82, 11.1, and 93.6%, respectively. Conclusions: Based on our results, MRI is the method of choice in terms of evaluating overall staging, as well as myometrial invasion, as its specificity and negative predictive value are relatively high. However, systematic lymphadenectomy showed improved cancer-related survival and recurrence-free survival. Our studies showed that the diagnosis of lymph node metastases is difficult with MRI modality since hyperplastic and metastatic nodes cannot easily differentiate, leading to a high percentage of false-positive results. Therefore, other imagingmodalitiesmay be used formore accurate evaluation. New findings of our study were that the role of the radiologist’s expertise in the evaluation of MR imaging plays an essential role in lowering false-negative and false-positive results. Therefore, findings evaluated by a radiologist with high-level expertise in gynecological imaging can complement the clinical findings and help substantially define the needed treatment.
C1 [Bus, Dorottya] Zala County Saint Rafael Hospital, Department of Obstetrics and GynecologyZalaegerszeg, Hungary.
[Nagy, Gyongyi] Zala Megyei Korhaz, RadiologiaZalaegerszeg, Hungary.
[Poka, Robert] University Medical School of Debrecen, Department of Gynecology and ObstetricsDebrecen, Hungary.
[Vajda, Gyorgy] University of Pecs, Faculty of Health SciencesPecs, Hungary.
RP Vajda, Gy (reprint author), University of Pecs, Faculty of Health Sciences, Pecs, Hungary.
EM drvagy11@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 611088
EP 611095
DI 10.3389/pore.2021.611088
PG 8
ER
PT J
AU Franzese, O
Di Francesco, A
Meco, D
Graziani, G
Cusano, G
Levati, L
Riccardi, R
Ruggiero, A
AF Franzese, Ornella
Di Francesco, M. Angela
Meco, Daniela
Graziani, Grazia
Cusano, Gabriella
Levati, Lauretta
Riccardi, Riccardo
Ruggiero, Antonio
TI hTERT Transduction Extends the Lifespan of Primary Pediatric Low-Grade Glioma Cells While Preserving the Biological Response to NGF
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE low-grade glioma; senescence; hTERT; NGF (nerve growth factor); differentiation
ID low-grade glioma; senescence; hTERT; NGF (nerve growth factor); differentiation
AB The neurotrophin nerve growth factor (NGF) modulates the growth of human gliomas and is able to induce cell differentiation through the engagement of tropomyosin receptor kinase A (TrkA) receptor, although the role played in controlling glioma survival has proved controversial. Unfortunately, the slow growth rate of low-grade gliomas (LGG) has made it difficult to investigate NGF effects on these tumors in preclinical models. In fact, patientderived low-grade human astrocytoma cells duplicate only a limited number of times in culture before undergoing senescence. Nevertheless, replicative senescence can be counteracted by overexpression of hTERT, the catalytic subunit of telomerase, which potentially increases the proliferative potential of human cells without inducing cancerassociated changes. We have extended, by hTERT transduction, the proliferative in vitro potential of a human LGG cell line derived from a pediatric pilocytic astrocytoma (PA) surgical sample. Remarkably, the hTERT-transduced LGG cells showed a behavior similar to that of the parental line in terms of biological responses to NGF treatment, including molecular events associated with induction of NGF-related differentiation. Therefore, transduction of LGG cells with hTERT can provide a valid approach to increase the in vitro life-span of patient-derived astrocytoma primary cultures, characterized by a finite proliferative potential.
C1 [Franzese, Ornella] University of Rome Tor Vergata, Department of Systems MedicineRome, Italy.
[Di Francesco, M. Angela] Fondazione Policlinico A. Gemelli, IRCCS, Institute of Internal Medicine, Periodic Fever and Rare Diseases CenterRome, Italy.
[Meco, Daniela] Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Oncologia PediatricaRome, Italy.
[Graziani, Grazia] University of Rome Tor Vergata, Department of Systems MedicineRome, Italy.
[Cusano, Gabriella] Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Oncologia PediatricaRome, Italy.
[Levati, Lauretta] IDI-IRCCS, Molecular Oncology LaboratoryRome, Italy.
[Riccardi, Riccardo] Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Oncologia PediatricaRome, Italy.
[Ruggiero, Antonio] Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Oncologia PediatricaRome, Italy.
RP Franzese, O (reprint author), University of Rome Tor Vergata, Department of Systems Medicine, Rome, Italy.
EM franzese@uniroma2.it
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 612375
EP 612386
DI 10.3389/pore.2021.612375
PG 12
ER
PT J
AU Wang, H
Yang, J
AF Wang, Huai
Yang, Jiankang
TI Colorectal Cancer that Highly Express Both ACE2 and TMPRSS2, Suggesting Severe Symptoms to SARS-CoV-2 Infection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SARS-COV-2; cancer; ACE2; TMPRSS2; colorectum
ID SARS-COV-2; cancer; ACE2; TMPRSS2; colorectum
AB The epidemic of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in the world pose a global health emergency. Cancer has been identified as a risk factor for the novel Coronavirus disease 2019 (COVID-19). The ACE2 and TMPRSS2 have been implicated in SARS-CoV-2 infection for mediating viral entry into the host cell. However, a systematic analysis of aberrant expression of ACE2 and TMPRSS2 was not yet reported in multiple human cancers. Here, we analyzed gene expression of ACE2 and TMPRSS2 across 31 types of tumors. Notably, overexpression of ACE2 and TMPRSS2 have been observed in colorectal cancer including colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). In addition, the colorectal tumors with upregulated gene expressing presented with decreased DNA methylation levels. DNA methylation might be one of the reasons for abnormal expression of ACE2 and TMPRSS2. Conclusively, colorectal cancer was the only cancer with the upregulated expression of ACE2 and TMPRSS2. More care of colorectal cancer patients is needed in multiple cancers affected by the COVID-19 outbreak.
C1 [Wang, Huai] Dali University, School of Basic Medical Sciences, Department of Biochemistry and Molecular BiologyDali, China.
[Yang, Jiankang] Dali University, School of Basic Medical Sciences, Department of Biochemistry and Molecular BiologyDali, China.
RP Yang, J (reprint author), Dali University, School of Basic Medical Sciences, Department of Biochemistry and Molecular Biology, Dali, China.
EM jkyang1984@126.com
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Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends onACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181:271–80., DOI 10.1016/j.cell.2020.02.052
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 612969
EP 612972
DI 10.3389/pore.2021.612969
PG 4
ER
PT J
AU Weidemann, S
Bohle, LJ
Contreras, H
Luebke, A
Kluth, M
Buscheck, F
Hube-Magg, C
Hoflmayer, D
Moller, K
Fraune, Ch
Bernreuther, Ch
Rink, M
Simon, R
Menz, A
Hinsch, A
Lebok, P
Clauditz, T
Sauter, G
Uhlig, R
Wilczak, W
Steurer, S
Burandt, E
Krech, R
Dum, D
Krech, T
Marx, A
Minner, S
AF Weidemann, Soren
Bohle, Lukas Jan
Contreras, Hendrina
Luebke, M. Andreas
Kluth, Martina
Buscheck, Franziska
Hube-Magg, Claudia
Hoflmayer, Doris
Moller, Katharina
Fraune, Christoph
Bernreuther, Christian
Rink, Michael
Simon, Ronald
Menz, Anne
Hinsch, Andrea
Lebok, Patrick
Clauditz, Till
Sauter, Guido
Uhlig, Ria
Wilczak, Waldemar
Steurer, Stefan
Burandt, Eike
Krech, Rainer
Dum, David
Krech, Till
Marx, Andreas
Minner, Sarah
TI Napsin A Expression in Human Tumors and Normal Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE napsin A; immunohistochemistry; tissue micro array; diagnostic; human cancer types
ID napsin A; immunohistochemistry; tissue micro array; diagnostic; human cancer types
AB Background: Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/TAO2) is a functional aspartic proteinase which is involved in the maturation of prosurfactant protein B in type II pneumocytes and the lysosomal protein catabolism in renal cells. Napsin A is highly expressed in adenocarcinomas of the lung and is thus commonly used to affirm this diagnosis. However, studies have shown that other tumors can also express Napsin A. Methods: To comprehensively determine Napsin A expression in normal and tumor tissue, 11,957 samples from 115 different tumor types and subtypes as well as 500 samples of 76 different normal tissue types were evaluable by immunohistochemistry on tissue microarrays. Results: Napsin A expression was present in 16 different tumor types. Adenocarcinoma of the lung (85.6%), clear cell adenocarcinoma of the ovary (71.7%), clear cell adenocarcinoma of the endometrium (42.8%), papillary renal cell carcinoma (40.2%), clear cell (tubulo) papillary renal cell carcinoma (16.7%), endometrial serous carcinoma (9.3%), papillary thyroid carcinoma (9.3%) and clear cell renal cell carcinoma (8.2%) were among the tumors with the highest prevalence of Napsin A positivity. In papillary and clear cell renal cell carcinoma, reduced Napsin A expression was linked to adverse clinicpathological features (p ≤ 0.03). Conclusion: This methodical approach enabled us to identify a ranking order of tumors according to their relative prevalence of Napsin A expression. The data also show that loss of Napsin A is linked to tumor dedifferentiation in renal cell carcinomas.
C1 [Weidemann, Soren] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Bohle, Lukas Jan] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Contreras, Hendrina] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Luebke, M. Andreas] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Kluth, Martina] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Buscheck, Franziska] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Hube-Magg, Claudia] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Hoflmayer, Doris] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Moller, Katharina] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Fraune, Christoph] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Bernreuther, Christian] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Rink, Michael] University Medical Center Hamburg-Eppendorf, Department of UrologyHamburg, Germany.
[Simon, Ronald] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Menz, Anne] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Hinsch, Andrea] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Lebok, Patrick] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Clauditz, Till] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Sauter, Guido] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Uhlig, Ria] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Wilczak, Waldemar] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Steurer, Stefan] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Burandt, Eike] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Krech, Rainer] Clinical Center Osnabrueck, Institute of PathologyOsnabrueck, Germany.
[Dum, David] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Krech, Till] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Marx, Andreas] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
[Minner, Sarah] University Medical Center Hamburg Eppendorf, PathologyHamburg, Germany.
RP Minner, S (reprint author), University Medical Center Hamburg Eppendorf, Pathology, Hamburg, Germany.
EM s.minner@uke.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 613099
EP 613110
DI 10.3389/pore.2021.613099
PG 12
ER
PT J
AU Varga, G
Toth, DA
Szita, RV
Csukly, Z
Hardi, A
Gaal-Weisinger, J
Nagy, Zs
Altai, E
Rencsik, A
Plander, M
Szendrei, T
Korad, K
Radvanyi, G
Rottek, J
Deak, B
Szaleczky, E
Schneider, T
Kohl, Z
Kosztolanyi, Sz
Alizadeh, H
Lengyel, Zs
Modok, Sz
Borbenyi, Z
Lovas, Sz
Varoczy, L
Illes,
Rajnics, P
Masszi, T
Mikala, G
AF Varga, Gergely
Toth, David Andras
Szita, Reka Virag
Csukly, Zoltan
Hardi, Apor
Gaal-Weisinger, Julia
Nagy, Zsolt
Altai, Elvira
Rencsik, Annamaria
Plander, Mark
Szendrei, Tamas
Korad, Krisztina
Radvanyi, Gaspar
Rottek, Janos
Deak, Beata
Szaleczky, Erika
Schneider, Tamas
Kohl, Zoltan
Kosztolanyi, Szabolcs
Alizadeh, Hussain
Lengyel, Zsuzsanna
Modok, Szabolcs
Borbenyi, Zita
Lovas, Szilvia
Varoczy, Laszlo
Illes, Arpad
Rajnics, Peter
Masszi, Tamas
Mikala, Gabor
TI Beneficial Effect of Lenalidomide-Dexamethason Treatment in Relapsed/Refractory Multiple Myeloma Patients: Results of Real-Life Data From 11 Hungarian Centers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE myeloma; lenalidomide; relapsed; real life; treatment
ID myeloma; lenalidomide; relapsed; real life; treatment
AB In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS (p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients.
C1 [Varga, Gergely] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Toth, David Andras] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Szita, Reka Virag] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Csukly, Zoltan] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Hardi, Apor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Gaal-Weisinger, Julia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Nagy, Zsolt] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Altai, Elvira] Veszprem- Csolnoky Ferenc County Hospital, HematologyVeszprem, Hungary.
[Rencsik, Annamaria] Veszprem- Csolnoky Ferenc County Hospital, HematologyVeszprem, Hungary.
[Plander, Mark] Vas County Markusovszky HospitalSzombathely, Hungary.
[Szendrei, Tamas] Vas County Markusovszky HospitalSzombathely, Hungary.
[Korad, Krisztina] County Hospital of Borsod-Abauj-ZemplenMiskolc, Hungary.
[Radvanyi, Gaspar] County Hospital of Borsod-Abauj-ZemplenMiskolc, Hungary.
[Rottek, Janos] National Institute of OncologyBudapest, Hungary.
[Deak, Beata] National Institute of OncologyBudapest, Hungary.
[Szaleczky, Erika] National Institute of OncologyBudapest, Hungary.
[Schneider, Tamas] National Institute of OncologyBudapest, Hungary.
[Kohl, Zoltan] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Kosztolanyi, Szabolcs] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Alizadeh, Hussain] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Lengyel, Zsuzsanna] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Modok, Szabolcs] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Lovas, Szilvia] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Rajnics, Peter] Kaposi Mor Teaching HospitalKaposvar, Hungary.
[Masszi, Tamas] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Varga, G (reprint author), Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary.
EM vargager@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 613264
EP 613269
DI 10.3389/pore.2021.613264
PG 6
ER
PT J
TI NOTCH Single Nucleotide Polymorphisms in the Predisposition of Breast and Colorectal Cancers in Saudi Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Notch; single nucleotide polymorphism; breast cancer; colorectal cancer; genetic screening marker
ID Notch; single nucleotide polymorphism; breast cancer; colorectal cancer; genetic screening marker
AB Breast cancer (BC) is a heterogeneous disease and is one of the most common malignancy affecting women worldwide while colorectal cancer (CRC) is estimated to be the third common cancer and second leading cause of cancer related death globally. Both BC and CRC involve multiple genetic and epigenetic alterations in genes belonging to various signaling pathways including NOTCH that has been implicated in the development of these cancers. We investigated four single nucleotide polymorphisms, each in genes encoding NOTCH1-4 receptors for their role in susceptibility to breast and colorectal cancers in Saudi population. In this case-control study, TaqMan genotypic analysis of rs3124591 in NOTCH1 and rs3820041 in NOTCH4 did not exhibit association with breast as well as colorectal cancers. However, a strong association of rs11249433 which is in close proximity to NOTCH2 was observed with breast cancer susceptibility especially with those having an early onset of the disease. Interestingly, the rs1043994 located in NOTCH3 showed gender preference and was found to be significantly associated with colorectal cancers in males. Validation of these findings in bigger populations of different ethnicities may prove beneficial in identifying rs11249433 and rs1043994 as genetic screening markers for early detection of breast and colorectal carcinomas, respectively.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 616204
EP 616214
DI 10.3389/pore.2021.616204
PG 11
ER
PT J
AU Nelhubel, Gy
Cserepes, M
Szabo, B
Turk, D
Karpati, A
Kenessey, I
Raso, E
Barbai, T
Hegedus, Z
Laszlo, V
Szokol, B
Dobos, J
Orfi, L
Tovari, J
AF Nelhubel, A. Gyorgyi
Cserepes, Mihaly
Szabo, Balazs
Turk, Dora
Karpati, Adel
Kenessey, Istvan
Raso, Erzsebet
Barbai, Tamas
Hegedus, Zita
Laszlo, Viktoria
Szokol, Balint
Dobos, Judit
Orfi, Laszlo
Tovari, Jozsef
TI EGFR Alterations Influence the Cetuximab Treatment Response and c-MET Tyrosine-Kinase Inhibitor Sensitivity in Experimental Head and Neck Squamous Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; c-Met; HNSCC; R521K; targeted tumor therapy
ID EGFR; c-Met; HNSCC; R521K; targeted tumor therapy
AB Background: Anti-EGFR antibody therapy is still one of the clinical choices in head and neck squamous cell carcinoma (HNSCC) patients, but the emergence of cetuximab resistance questioned its effectiveness and reduced its applicability. Although several possible reasons of resistance against the antibody treatment and alternative therapeutic proposals have been described (EGFR alterations, activation of other signaling pathways), there is no method to predict the effectiveness of anti-EGFR antibody treatments and to suggest novel therapeutics. Our study investigated the effect of EGFR R521K alteration on efficiency of cetuximab therapy of HNSCC cell lines and tried to find alternative therapeutic approaches against the resistant cells. Methods: After genetic characterization of HNSCC cells, we chose one wild type and one R521K+ cell line for in vitro proliferation and apoptosis tests, and in vivo animal models using different therapeutic agents. Results: Although the cetuximab treatment affected EGFR signalization in both cells, it did not alter in vitro cell proliferation or apoptosis. In vivo cetuximab therapy was also ineffective on R521K harboring tumor xenografts, while blocked the tumor growth of EGFR-wild type xenografts. Interestingly, the cetuximab-resistant R521K tumors were successfully treated with c-MET tyrosine kinase inhibitor SU11274. Conclusion: Our results suggest that HNSCC cell line expressing the R521K mutant form of EGFR does not respond well to cetuximab treatment in vitro or in vivo, but hopefully might be targeted by c-MET tyrosine kinase inhibitor treatment.
C1 [Nelhubel, A. Gyorgyi] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Cserepes, Mihaly] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Szabo, Balazs] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Turk, Dora] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Karpati, Adel] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Kenessey, Istvan] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Raso, Erzsebet] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Barbai, Tamas] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Hegedus, Zita] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
[Laszlo, Viktoria] Medical University of Vienna, Department of Thoracic SurgeryVienna, Austria.
[Szokol, Balint] Vichem Kft.Budapest, Hungary.
[Dobos, Judit] Vichem Kft.Budapest, Hungary.
[Orfi, Laszlo] Vichem Kft.Budapest, Hungary.
[Tovari, Jozsef] National Institute of Oncology, Center of Diagnostic and Experimental TumorpathologyBudapest, Hungary.
RP Tovari, J (reprint author), National Institute of Oncology, Center of Diagnostic and Experimental Tumorpathology, Budapest, Hungary.
EM tozsi@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 620256
EP 620268
DI 10.3389/pore.2021.620256
PG 13
ER
PT J
TI Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE diffuse gastric cancer; SUN-16 cells; estrogen; ovariectomized mice; cancer xenograft model
ID diffuse gastric cancer; SUN-16 cells; estrogen; ovariectomized mice; cancer xenograft model
AB Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancerrelated deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffusetype gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 622733
EP 622741
DI 10.3389/pore.2021.622733
PG 9
ER
PT J
AU Rossouw, S
Bendou, H
Blignaut, R
Bell, L
Rigby, J
Christoffels, A
AF Rossouw, C. Sophia
Bendou, Hocine
Blignaut, J. Renette
Bell, Liam
Rigby, Jonathan
Christoffels, Alan
TI Evaluation of Protein Purification Techniques and Effects of Storage Duration on LC-MS/MS Analysis of Archived FFPE Human CRC Tissues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE formalin-fixed paraffin-embedded proteomics; acetone precipitation and formic acid resolubilization; detergent removal plates; SP3/HILIC-on-bead-digestion; mass spectrometry; LC-MS/MS
ID formalin-fixed paraffin-embedded proteomics; acetone precipitation and formic acid resolubilization; detergent removal plates; SP3/HILIC-on-bead-digestion; mass spectrometry; LC-MS/MS
AB To elucidate cancer pathogenesis and its mechanisms at the molecular level, the collecting and characterization of large individual patient tissue cohorts are required. Since most pathology institutes routinely preserve biopsy tissues by standardized methods of formalin fixation and paraffin embedment, these archived FFPE tissues are important collections of pathology material that include patient metadata, such as medical history and treatments. FFPE blocks can be stored under ambient conditions for decades, while retaining cellular morphology, due to modifications induced by formalin. However, the effect of long-term storage, at resource-limited institutions in developing countries, on extractable protein quantity/quality has not yet been investigated. In addition, the optimal sample preparation techniques required for accurate and reproducible results from label-free LC-MS/MS analysis across block ages remains unclear. This study investigated protein extraction efficiency of 1, 5, and 10-year old human colorectal carcinoma resection tissue and assessed three different gel-free protein purification methods for label-free LC-MS/MS analysis. A sample size of n = 17 patients per experimental group (with experiment power = 0.7 and α = 0.05, resulting in 70% confidence level) was selected. Data were evaluated in terms of protein concentration extracted, peptide/protein identifications, method reproducibility and efficiency, sample proteome integrity (due to storage time), as well as protein/peptide distribution according to biological processes, cellular components, and physicochemical properties. Data are available via ProteomeXchange with identifier PXD017198. The results indicate that the amount of protein extracted is significantly dependent on block age (p < 0.0001), with older blocks yielding less protein than newer blocks. Detergent removal plates were the most efficient and overall reproducible protein purification method with regard to number of peptide and protein identifications, followed by the MagReSyn® SP3/HILIC method (with on-bead enzymatic digestion), and lastly the acetone precipitation and formic acid resolubilization method. Overall, the results indicate that long-term storage of FFPE tissues (as measured by methionine oxidation) does not considerably interfere with retrospective proteomic analysis (p > 0.1). Block age mainly affects initial protein extraction yields and does not extensively impact on subsequent label-free LC-MS/MS analysis results.
C1 [Rossouw, C. Sophia] University of the Western Cape, South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics UnitBellville, South Africa.
[Bendou, Hocine] University of the Western Cape, South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics UnitBellville, South Africa.
[Blignaut, J. Renette] University of the Western Cape, Department of Statistics and Population StudiesBellville, South Africa.
[Bell, Liam] Centre for Proteomic and Genomic Research, ObservatoryCape Town, South Africa.
[Rigby, Jonathan] National Health Laboratory Service, Tygerberg Hospital, Faculty of Health Sciences, University of Stellenbosch, Division of Anatomical Pathology, Department of PathologyCape Town, South Africa.
[Christoffels, Alan] University of the Western Cape, South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics UnitBellville, South Africa.
RP Christoffels, A (reprint author), University of the Western Cape, South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics Unit, Bellville, South Africa.
EM alan@sanbi.ac.za
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 622855
EP 622874
DI 10.3389/pore.2021.622855
PG 20
ER
PT J
TI Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TRAF2; TRAF3; mutation; cancer; expression
ID TRAF2; TRAF3; mutation; cancer; expression
AB TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68microsatellite-stable (MSS)CCs).Weidentified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs,we analyzed the mutations inmulti-regions for 39CCs (16MSI-Hand23MSSCCs), and discovered that 12.5% (2/16) and 6.3%(1/16) ofMSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present inMSI-H CCs, which could contribute toMSI-H cancer development.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 625438
EP 625443
DI 10.3389/pore.2021.625438
PG 6
ER
PT J
AU Kong, J
Yuan, X
Wang, J
Liu, Y
Sun, W
Gu, B
Lan, Z
Gao, Sh
AF Kong, Jinyu
Yuan, Xiang
Wang, Jian
Liu, Yiwen
Sun, Wei
Gu, Bianli
Lan, Zijun
Gao, Shegan
TI Frequencies of Porphyromonas gingivalis Detection in Oral-Digestive Tract Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Porphyromonas gingivalis; oral squamous cell carcinoma; oesophageal squamous cell carcinoma; digestive tract cancer; prognosis
ID Porphyromonas gingivalis; oral squamous cell carcinoma; oesophageal squamous cell carcinoma; digestive tract cancer; prognosis
AB Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. In this study, we examined the presence of Porphyromonas gingivalis (P. gingivalis) in oral-digestive tract tumors by immunohistochemistry (IHC) and PCR and analyzed the correlation between P. gingivalis detection and clinicopathological characteristics and prognosis of oral and esophageal carcinoma. The IHC results showed that the positive rates of P. gingivalis were 60.00, 46.00, 20.00, 6.67, and 2.86% in oral, esophagus, cardiac, stomach, and colorectal cancer tissues, respectively. Likewise, PCR results showed rates of 56.00, 42.00, 16.67, 3.33, and 2.86%, respectively. The two methods were consistent, and the kappa value was 0.806, P < 0.001. In addition, P. gingivalis expression was significantly correlated with lymph node metastasis and the clinical stages of oral and esophageal cancer (P < 0.05). The overall survival rate of the P. gingivalis undetected group (86, 50%) was significantly higher than that of the P. gingivalis detected group (57, 14%) for oral and esophageal cancer, respectively. In conclusion, the detection rate of P. gingivalis showed a decreasing trend in oral-digestive tract tumors. Detection with P. gingivalis was associated with poor prognosis for oral and esophageal cancer.
C1 [Kong, Jinyu] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Yuan, Xiang] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Wang, Jian] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Radiodiagnosis CenterLuoyang, China.
[Liu, Yiwen] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Sun, Wei] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Gu, Bianli] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Lan, Zijun] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
[Gao, Shegan] The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer InstituteLuoyang, China.
RP Gao, Sh (reprint author), The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Cancer Institute, Luoyang, China.
EM gsg112258@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 628942
EP 628950
DI 10.3389/pore.2021.628942
PG 9
ER
PT J
AU Chung, SM
Choi, JY
Lee, SY
Yoon, IB
Ha, US
AF Chung, Su Mun
Choi, Jin Yeong
Lee, Sub Young
Yoon, Il Byung
Ha, U-Syn
TI How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostatic neoplasms; prostatectomy; neoplasm grading; gleason score; neoplasm invasiveness
ID prostatic neoplasms; prostatectomy; neoplasm grading; gleason score; neoplasm invasiveness
AB Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.
C1 [Chung, Su Mun] Catholic Kwandong University, International St. Mary’s Hospital, Department of UrologyIncheon, South Korea.
[Choi, Jin Yeong] The Catholic University of Korea, College of Medicine, Seoul St. Mary’s HospitalSeoul, South Korea.
[Lee, Sub Young] The Catholic University of Korea, College of Medicine, Eunpyeong St. Mary’s HospitalSeoul, South Korea.
[Yoon, Il Byung] Catholic Kwandong University, International St. Mary’s Hospital, Department of UrologyIncheon, South Korea.
[Ha, U-Syn] The Catholic University of Korea, College of Medicine, Seoul St. Mary’s HospitalSeoul, South Korea.
RP Yoon, IB (reprint author), Catholic Kwandong University, International St. Mary’s Hospital, Department of Urology, Incheon, South Korea.
EM yoonbi0948@catholic.ac.kr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 629489
EP 629495
DI 10.3389/pore.2021.629489
PG 7
ER
PT J
AU Zhou, J
Zhang, Sh
Sun, X
Lou, Y
Yu, J
AF Zhou, Jingbo
Zhang, Shu
Sun, Xinyi
Lou, Yan
Yu, Jiangyi
TI Hyperoside Protects HK-2 Cells Against High Glucose-Induced Apoptosis and Inflammation via the miR-499a-5p/NRIP1 Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hyperoside; HK-2 cells; apoptosis; inflammation; molecular biology
ID hyperoside; HK-2 cells; apoptosis; inflammation; molecular biology
AB Hyperoside, a flavonol glycoside, is derived from plants of the genera Hypericum and Crataegus. Recent studies have indicated the anti-apoptotic and anti-inflammatory roles of hyperoside. The present study was designed to measure the effects of hyperoside on high glucose (HG)-treated HK-2 cells. HK-2 is a human papillomavirus 16 transformed cell line and can be used as a model for normal tubular cell. Cell apoptosis was examined by TUNEL assays and flow cytometry analysis. Inflammatory response was detected by Enzyme linked immunosorbent assay kits. Western blotting was applied to detect protein levels of apoptosis-related genes and inflammatory cytokines. Mechanistical assays including luciferase reporter and RNA pull down assays were applied to detect the binding relationship between molecules. We identified that hyperoside protected HK-2 cells against HG-induced apoptosis and inflammation. Moreover, miR-499a-5p was upregulated by hyperoside in a dose dependent manner. MiR-499a-5p inhibition rescued the suppressive effects of hyperoside on apoptosis and inflammation of HGtreated HK-2 cells. Furthermore, miR-499a-5p targeted NRIP1 to inhibit its mRNA expression, and further suppressed its translation. NRIP1 was downregulated by hyperoside in a dose dependent manner. Finally, rescue assays indicated that miR-499a-5p inhibition rescued the protective effects of hyperoside on apoptosis and inflammatory response of HK-2 cells by NRIP1. In conclusion, our findings revealed that hyperoside alleviates HG-induced apoptosis and inflammatory response of HK-2 cells by the miR-499a-5p/NRIP1 axis.
C1 [Zhou, Jingbo] Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Department of EndocrinologyNanjing, China.
[Zhang, Shu] Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Department of EndocrinologyNanjing, China.
[Sun, Xinyi] Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Department of EndocrinologyNanjing, China.
[Lou, Yan] Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Department of EndocrinologyNanjing, China.
[Yu, Jiangyi] Jiangsu Provincial Hospital of Traditional Chinese Medicine, Department of EndocrinologyNanjing, China.
RP Yu, J (reprint author), Jiangsu Provincial Hospital of Traditional Chinese Medicine, Department of Endocrinology, Nanjing, China.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 629829
EP 629837
DI 10.3389/pore.2021.629829
PG 9
ER
PT J
AU Valdivia, D
Cheufou, D
Fels, B
Puhlvers, S
Mardanzai, K
Zaatar, M
Weinreich, G
Taube, Ch
Theegarten, D
Stuschke, M
Schuler, M
Stamatis, G
Hegedus, B
Aigner, C
AF Valdivia, Daniel
Cheufou, Danjouma
Fels, Benjamin
Puhlvers, Stephan
Mardanzai, Khaled
Zaatar, Mohamed
Weinreich, Gerhard
Taube, Christian
Theegarten, Dirk
Stuschke, Martin
Schuler, Martin
Stamatis, Georgios
Hegedus, Balazs
Aigner, Clemens
TI Potential Prognostic Value of Preoperative Leukocyte Count, Lactate Dehydrogenase and C-Reactive Protein in Thymic Epithelial Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE thymoma; thymic epithelial tumor; thymectomy; LDH; CRP; C-reactive protein
ID thymoma; thymic epithelial tumor; thymectomy; LDH; CRP; C-reactive protein
AB Thymic epithelial tumors are the most common mediastinal tumors. Surgery is the mainstay of treatment and complete resection provides the best survival rate. However, advanced tumors often require multimodality treatment and thus we analyzed the prognostic potential of routine circulating biomarkers that might help to risk-stratify patients beyond tumor stage and histology. Preoperative values for white blood cell count (WBC), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were analyzed in 220 thymic epithelial tumor patients operated between 1999 and 2018. Increased CRP levels (>1 mg/dl) were significantly more often measured in thymic carcinoma and neuroendocrine tumors when compared to thymoma. LDH serum activity was higher in thymic neuroendocrine tumors when compared to thymoma or thymic carcinoma. The median disease specific survival was significantly longer in thymoma cases than in thymic carcinoma and neuroendocrine tumors. Increased preoperative LDH level (>240 U/L) associated with shorter survival in thymus carcinoma (HR 4.76, p = 0.0299). In summary, higher CRP associated with carcinoma and neuroendocrine tumors, while LDH increased primarily in neuroendocrine tumors suggesting that biomarker analysis should be performed in a histology specific manner. Importantly, preoperative serum LDH might be a prognosticator in thymic carcinoma and may help to risk stratify surgically treated patients in multimodal treatment regimens.
C1 [Valdivia, Daniel] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Cheufou, Danjouma] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Fels, Benjamin] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Puhlvers, Stephan] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Mardanzai, Khaled] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Zaatar, Mohamed] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Weinreich, Gerhard] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of PulmonologyEssen, Germany.
[Taube, Christian] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of PulmonologyEssen, Germany.
[Theegarten, Dirk] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Stuschke, Martin] University Duisburg-Essen, West German Cancer Center, University Hospital Essen, Department of Radiation OncologyEssen, Germany.
[Schuler, Martin] University Duisburg- Essen, West German Cancer Center, University Hospital Essen, Department of Medical OncologyEssen, Germany.
[Stamatis, Georgios] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Balazs] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Aigner, Clemens] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
RP Aigner, C (reprint author), University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic Surgery, Essen, Germany.
EM clemens.aigner@rlk.uk-essen.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 629993
EP 630001
DI 10.3389/pore.2021.629993
PG 9
ER
PT J
AU Szekely, R
Suhai, IF
Karlinger, K
Baksa, G
Szabaczki, B
Barany, L
Poloskei, G
Racz, G
Wagner,
Merkely, B
Ruttkay, T
AF Szekely, Reka
Suhai, Imre Ferenc
Karlinger, Kinga
Baksa, Gabor
Szabaczki, Bence
Barany, Laszlo
Poloskei, Gergely
Racz, Gergely
Wagner, Odon
Merkely, Bela
Ruttkay, Tamas
TI Human Cadaveric Artificial Lung Tumor-Mimic Training Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor mimic; pseudotumor; cadaver workshop; hands-on training; lung tumor
ID tumor mimic; pseudotumor; cadaver workshop; hands-on training; lung tumor
AB Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice. Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions–apical, hilar and two peripheral–were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers. Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumormimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features. Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.
C1 [Szekely, Reka] Semmelweis University, Department of Anatomy, Histology and Embryology, Laboratory for Applied and Clinical AnatomyBudapest, Hungary.
[Suhai, Imre Ferenc] Semmelweis University, Department of Cardiovascular SurgeryBudapest, Hungary.
[Karlinger, Kinga] Semmelweis University, Medical Imaging CenterBudapest, Hungary.
[Baksa, Gabor] Semmelweis University, Department of Anatomy, Histology and Embryology, Laboratory for Applied and Clinical AnatomyBudapest, Hungary.
[Szabaczki, Bence] Semmelweis University, Department of Anatomy, Histology and Embryology, Laboratory for Applied and Clinical AnatomyBudapest, Hungary.
[Barany, Laszlo] Semmelweis University, Department of Anatomy, Histology and Embryology, Laboratory for Applied and Clinical AnatomyBudapest, Hungary.
[Poloskei, Gergely] Semmelweis University, Medical Imaging CenterBudapest, Hungary.
[Racz, Gergely] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Wagner, Odon] Budapest University of Technology and Economics, Department of Inorganic and Analytical ChemistryBudapest, Hungary.
[Merkely, Bela] Semmelweis University, Department of Cardiovascular SurgeryBudapest, Hungary.
[Ruttkay, Tamas] Semmelweis University, Department of Anatomy, Histology and Embryology, Laboratory for Applied and Clinical AnatomyBudapest, Hungary.
RP Racz, G (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM racz.gergely@med.semmelweisuniv.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 630459
EP 630466
DI 10.3389/pore.2021.630459
PG 8
ER
PT J
AU Yang, A
Li, M
Fang, M
AF Yang, Ai
Li, Min
Fang, Mingzhi
TI The Research Progress of Direct KRAS G12C Mutation Inhibitors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE KRAS mutation; targeted drugs; oncogene; inhibitor; oncology
ID KRAS mutation; targeted drugs; oncogene; inhibitor; oncology
AB KRAS mutations have long been considered undruggable. However, a series of direct KRAS mutation inhibitors have been developed since the switch II pocket was discovered recently. This review will summarize progress in the development of direct KRAS G12C mutation inhibitors, current relevant drugs under study and challenges that need to be considered in future research.
C1 [Yang, Ai] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
[Li, Min] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
[Fang, Mingzhi] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
RP Li, M (reprint author), Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of Oncology, Nanjing, China.
EM doctorlimin@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 631095
EP 631102
DI 10.3389/pore.2021.631095
PG 8
ER
PT J
AU Puskas, R
Bikov, A
Horvath, P
Lazar, Zs
Kunos, L
Nagy, R
Pinter, G
Galffy, G
AF Puskas, Rita
Bikov, Andras
Horvath, Peter
Lazar, Zsofia
Kunos, Laszlo
Nagy, Reka
Pinter, Gabriella
Galffy, Gabriella
TI Circulating Survivin Protein Levels in Lung Cancer Patients Treated With Platinum-Based Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survivin; lung cancer; ELISA; disease progression; biomarker
ID survivin; lung cancer; ELISA; disease progression; biomarker
AB The survivin protein contributes to the development and progression of tumors. Protein expression and mRNA levels correlate with clinicopathological parameters and survival of cancer patients. Our purpose was to evaluate whether circulating survivin levels have any diagnostic or predictive value in lung cancer. 118 patients with advanced stage lung cancer participated in our study. 53 suffered from adenocarcinoma (ADC), 33 from squamous cell carcinoma (SqCC), and 32 from small cell lung cancer (SCLC). We also enrolled 21 control subjects. Blood samples were collected before and after two cycles of chemotherapy. We measured survivin concentrations with ELISA. Non-parametric tests were used for analysis. We did not find significant difference in survivin levels between patients and control subjects (17.19/0–829.74/vs. 49.13/0–165.92/pg/ml; p = 0.07). We found lower survivin concentrations in patients with SqCC (0/0–171.24/ pg/ml) than in those with ADC (24.94/0–626.46 pg/ml) and SCLC (45.51/0–829.74/pg/ ml) (ADC vs. SqCC p < 0.0001, ADC vs. SCLC p = 0.0405, SqCC vs. SCLC p < 0.0001). Survivin levels were higher in stage IV patients than in patients without distant metastases (p = 0.0061), and concentrations were progressively higher with increasing number of metastatic organ sites (p = 0.04). We observed a decrease in survivin levels in ADC patients after platinum plus pemetrexed chemotherapy (26.22/0–626.46/pg/ml before vs. 0/0–114.36/pg/ml after; p = 0.01). Neither progression-free nor overall survival correlated with survivin levels at baseline. Our data imply that survivin may be involved in the development of metastases and it might be used as a biomarker of disease progression. However, circulating survivin concentrations do not predict survival of patients with lung cancer.
C1 [Puskas, Rita] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Bikov, Andras] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Horvath, Peter] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Lazar, Zsofia] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Kunos, Laszlo] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Nagy, Reka] Semmelweis UniversityBudapest, Hungary.
[Pinter, Gabriella] Semmelweis UniversityBudapest, Hungary.
[Galffy, Gabriella] Semmelweis University, Department of PulmonologyBudapest, Hungary.
RP Puskas, R (reprint author), Semmelweis University, Department of Pulmonology, Budapest, Hungary.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 631969
EP 631975
DI 10.3389/pore.2021.631969
PG 7
ER
PT J
AU Wang, X
Liu, Y
Leng, X
Cao, K
Sun, W
Zhu, J
Ma, J
AF Wang, Xiaoyuan
Liu, Yang
Leng, Xue
Cao, Kui
Sun, Wentao
Zhu, Jinhong
Ma, Jianqun
TI UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE UBE2T; ESCC; prognosis; TCGA; immunohistochemistry
ID UBE2T; ESCC; prognosis; TCGA; immunohistochemistry
AB Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC). Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA–ESCC cohort. Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and highrisk groups with significantly different overall survival in the TCGA–ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group. Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.
C1 [Wang, Xiaoyuan] Harbin Medical University Cancer Hospital, Department of Thoracic SurgeryHarbin, China.
[Liu, Yang] Harbin Medical University, Cancer Hospital, Department of Medical OncologyHarbin, China.
[Leng, Xue] Harbin Medical University Cancer Hospital, Department of Thoracic SurgeryHarbin, China.
[Cao, Kui] Harbin Medical University, Cancer Hospital, Department of Medical OncologyHarbin, China.
[Sun, Wentao] Harbin Medical University Cancer Hospital, Department of RadiologyHarbin, China.
[Zhu, Jinhong] Harbin Medical University Cancer Hospital, Department of Clinical LaboratoryHarbin, China.
[Ma, Jianqun] Harbin Medical University Cancer Hospital, Department of Thoracic SurgeryHarbin, China.
RP Zhu, J (reprint author), Harbin Medical University Cancer Hospital, Department of Clinical Laboratory, Harbin, China.
EM jinhongzhu625@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 632531
EP 632544
DI 10.3389/pore.2021.632531
PG 14
ER
PT J
AU Uchida, Sh
Kojima, T
Sugino, T
AF Uchida, Shiro
Kojima, Takaaki
Sugino, Takashi
TI Clinicopathological Features, Tumor Mutational Burden, and Tumour-Infiltrating Lymphocyte Interplay in ERBB2-Mutated Breast Cancer: In Silico Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Breast cancer; ErbB2 mutation; tumor mutational burden; tumour-infiltrating lymphocytes; Bioinformactics analysis
ID Breast cancer; ErbB2 mutation; tumor mutational burden; tumour-infiltrating lymphocytes; Bioinformactics analysis
AB Recent evidence suggests that somatic mutations in ERBB2 activate ERBB2 signaling. These mutations occur at a frequency of approximately 3% in breast cancer (BC). ERBB2 mutations indicate poor prognosis as they are associated with recurrence and metastasis. This study aimed to evaluate the clinicopathological features, immune infiltration levels, tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in ERBB2-mutated breast cancer (ERBB2-mutated BC) using a bioinformatic approach and publicly available datasets (i.e., TCGA-BRCA and TIMER2.0). ERBB2-mutated BCs were associated with a high histological grade. ERBB2-mutated BCs comprised invasive breast carcinoma of no special type (21/35, 60%), classic invasive lobular carcinoma (12/35, 34.3%), and pleomorphic invasive lobular carcinoma (2/35, 5.7%). A Kaplan-Meier survival curve demonstrated that ERBB2-mutated BC was associated with a significantly worse prognosis compared to ERBB2 non-mutated BC (p < 0.01). Furthermore, 40% (14/35) of the patients with ERBB2-mutated BC harbored CDH1 mutations. Mutations at L755 and V777 accounted for 30.5% of these mutations in ERBB2-mutated BC, suggesting that these sites are mutational hot spots in BC, particularly in invasive lobular carcinoma. Of the ERBB2-mutated BCs, 8.6% were classified as TIL-high, whereas 77.1% were TILs-low; TMB significantly correlated with TILs (p < 0.05). CD8+ T cell infiltration levels were significantly higher in ERBB2 nonmutated BC. Among ERBB2-mutated BCs, 22.9% were classified as TMB-high, which was significantly higher than the rate in the ERBB2 non-mutated BC (p < 0.01). These findings provide evidence for a link between ERBB2 mutations and high TMB in BC.
C1 [Uchida, Shiro] Kikuna Memorial Hospital, Division of Diagnostic PathologyYokohama, Japan.
[Kojima, Takaaki] Nagoya University, Graduate School of Bioagricultural SciencesNagoya, Japan.
[Sugino, Takashi] Shizuoka Cancer Center, Division of PathologyShizuoka, Japan.
RP Uchida, Sh (reprint author), Kikuna Memorial Hospital, Division of Diagnostic Pathology, Yokohama, Japan.
EM Dr.Uchida@gmail.com
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Gonzalez-Ericsson PI, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, et al. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice. J Pathol, 2020, 250:667–84., DOI 10.1002/path.5406
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol, 2018, 19:40–50., DOI 10. 1016/s1470-2045(17)30904-x
Stanton SE, Adams S, Disis ML. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes. JAMA Oncol, 2016, 2:1354–60., DOI 10.1001/jamaoncol.2016.1061
Merino DM, McShane L, Butler M, Funari VA, Hellmann MD, Chaudhary R, et al. TMB standardization by alignment to reference standards: phase II of the friends of cancer research TMB harmonization project. J Clin Oncol, 2019, 37: 2631., DOI 10.1200/jco.2019.37.15_suppl.2624
Jain MS, Massoud TF. Predicting tumour mutational burden from histopathological images using multiscale deep learning. Nat Mach Intell, 2020, 2:356–62., DOI 10.1038/s42256-020-0190-5
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 633243
EP 633251
DI 10.3389/pore.2021.633243
PG 9
ER
PT J
AU Zhang, Y
Qin, Y
Xu, H
Yao, Q
Gao, Y
Feng, Y
Ren, J
AF Zhang, Yan
Qin, Yaping
Xu, Hongen
Yao, Qihui
Gao, Yalan
Feng, Yushu
Ren, Jingli
TI Case Report: A Case Report of a Histological Transformation of ALK-Rearranged Adenocarcinoma With High Expression of PD-L1 to Squamous Cell Carcinoma After Treatment With Alectinib
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE ALK-Rearranged adenocarcinoma; PD-L1; squamous cell carcinoma; alectinib; histological transformation
ID ALK-Rearranged adenocarcinoma; PD-L1; squamous cell carcinoma; alectinib; histological transformation
AB We report an anaplastic lymphoma kinase (ALK)-positive patient shows a poor response to the ALK inhibitor alectinib due to the high expression of programmed death-ligand 1 (PDL1). After treatment with alectinib, the pathological form changed from adenocarcinoma into squamous cell carcinoma without novel genetic changes. This case may reveal a direct relationship between ALK mutation and a high level of PD-L1 expression.
C1 [Zhang, Yan] The Second Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Qin, Yaping] The Second Affiliated Hospital of Zhengzhou University, Department of Precision Medicine CenterZhengzhou, China.
[Xu, Hongen] The Second Affiliated Hospital of Zhengzhou University, Department of Precision Medicine CenterZhengzhou, China.
[Yao, Qihui] The Second Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Gao, Yalan] The Second Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Feng, Yushu] The Second Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Ren, Jingli] The Second Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
RP Ren, J (reprint author), The Second Affiliated Hospital of Zhengzhou University, Department of Pathology, Zhengzhou, China.
EM jingliren123002@126.com
CR Kwak LE, Shaw AT, Ou S-HI, Bang YJ, Janne PA, Haber DA, et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. New Engl J Med, 2011). 364(6):588., DOI 10.1056/NEJMoa1006448
Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim D-W, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med, 2017). 377(9):829–38., DOI 10.1056/ nejmoa1704795
Yang CY, Liao WY, Ho CC, Chen KY, Tsai TH, Hsu CL, et al. Association of programmed death-ligand 1 expression with fusion variants and clinical outcomes in patients with anaplastic lymphoma kinase-positive lung adenocarcinoma receiving crizotinib. Oncologist, 2020). 25(8):702–11., DOI 10. 1634/theoncologist.2020-0088
Muller IB, de Langen AJ, Giovannetti E, Peters GJ. Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib. Onco Targets Ther, 2017). 10:4535–41., DOI 10.2147/ott.s109493
Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res, 2012). 18(5): 1472–82., DOI 10.1158/1078-0432.ccr-11-2906
Lovly CM, Mcdonald NT, Chen H, Ortiz-Cuaran S, Heukamp LC, Yan Y, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med, 2014). 20(9):1027–34., DOI 10.1038/nm.3667
Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science, 2014). 346(6216):1480–6., DOI 10.1126/ science.1254721
Hrustanovic G, Olivas V, Pazarentzos E, Tulpule A, Asthana S, Blakely CM, et al. RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer. Nat Med, 2015). 21(9):1038–47., DOI 10.1038/ nm.3930
Fujita S, Masago K, Katakami N, Yatabe Y. Transformation to SCLC after treatment with the ALK inhibitor alectinib. J Thorac Oncol, 2016). 11(6): e67–e72., DOI 10.1016/j.jtho.2015.12.105
Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res, 2013). 19(8):2240–7., DOI 10.1158/1078-0432.ccr-12-2246
Sequist LV, Waltman BA, Dias-Santagata D, Digumaethy S, Turke AB, Fidias P, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Translational Med, 2011). 3(75):26r–75r., DOI 10.1126/scitranslmed.3002003
Mamesaya N, Nakashima K, Naito T, Nakajima T, Endo M, Takahashi T. ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature. BMC Cancer, 2017). 17(1):471., DOI 10.1186/ s12885-017-3468-1
Sagawa R, Ohba T, Ito E, Isogai S. ALK-positive squamous cell carcinoma dramatically responded to alectinib. Case Rep Oncol Med, 2018). 2018:1–3., DOI 10.1155/2018/4172721
Hsu K-H, Huang Y-H, Tseng J-S, Chen K-C, Ku W-H, Su K-Y, et al. High PD-L1 expression correlates with primary resistance to EGFRTKIs in treatment naive advanced EGFR-mutant lung adenocarcinoma patients. Lung Cancer, 2019). 127:37–43., DOI 10.1016/j.lungcan.2018. 11.021
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 637745
EP 637750
DI 10.3389/pore.2021.637745
PG 6
ER
PT J
AU Safi, M
Trapani, D
Alradhi, M
Shan, X
Jiwei, L
AF Safi, Mohammed
Trapani, Dario
Alradhi, Mohammed
Shan, Xiu
Jiwei, Liu
TI No Overall Survival Difference in the Immunotherapy Era for Rare Subtypes of Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE melanoma; SEER database; immunotherapy; survival; epidimiology
ID melanoma; SEER database; immunotherapy; survival; epidimiology
C1 [Safi, Mohammed] The First Affiliated Hospital of Dalian Medical University, Department of OncologyDalian, China.
[Trapani, Dario] European Institute of OncologyMilan, Italy.
[Alradhi, Mohammed] Dalian Medical University, The Second HospitalDalian, China.
[Shan, Xiu] The First Affiliated Hospital of Dalian Medical University, Department of OncologyDalian, China.
[Jiwei, Liu] The First Affiliated Hospital of Dalian Medical University, Department of OncologyDalian, China.
RP Safi, M (reprint author), The First Affiliated Hospital of Dalian Medical University, Department of Oncology, Dalian, China.
EM Mhosafi86@gmail.com
CR Uprety D, Bista A, Chennamadhavuni A, Niroula A, Jafri SIM, Smith A, et al. Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study. Melanoma Res, 2018, 28(1):56–60., DOI 10.1097/cmr.0000000000000394
RodriguesM, de Koning L, Coupland S, Jochemsen A,Marais R, SternM-H, et al. So close, yet so far: discrepancies between uveal and othermelanomas. A position paper from um cure 2020. Cancers, 2019, 11(7):1032., DOI 10.3390/cancers11071032
Alicea GM, Rebecca VW. Emerging strategies to treat rare and intractable subtypes of melanoma. Pigment Cel Melanoma Res., 2021, 34(1):44–58., DOI 10.1111/pcmr.12880
Rapisuwon S, Qin Y, Roszik J, Carapeto F, Patel S, Carvajal RD. Systemic therapy for mucosal, acral, and uveal melanoma. Cutan Melanoma, 2020, 1301–35., DOI 10.1007/978-3-030-05070-2_62
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 639004
EP 639005
DI 10.3389/pore.2021.639004
PG 2
ER
PT J
AU Krokker, L
Szabo, B
Nemeth, K
Tohati, R
Sarkadi, B
Meszaros, K
Patocs, A
Butz, H
AF Krokker, Lilla
Szabo, Borbala
Nemeth, Kinga
Tohati, Rebeka
Sarkadi, Balazs
Meszaros, Katalin
Patocs, Attila
Butz, Henriett
TI Three Dimensional Cell Culturing for Modeling Adrenal and Pituitary Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE 3D cell culture; adrenal tumor; adrenocortical carcinoma; pheochromocytoma; pitNET; pituitary adenoma
ID 3D cell culture; adrenal tumor; adrenocortical carcinoma; pheochromocytoma; pitNET; pituitary adenoma
AB In vitro monolayer conditions are not able to reproduce the complexity of solid tumors, still, there is scarce information about the 3D cell culture models of endocrine tumor types. Therefore, our aim was to develop in vitro 3D tumor models by different methodologies for adrenocortical carcinoma (H295R), pituitary neuroendocrine tumor (RC-4B/C and GH3) and pheochromocytoma (PC-12). Various methodologies were tested. Cell biological assays (cell viability, proliferation and live cell ratio) and steroid hormone production by HPLC-MS/MS method were applied to monitor cellular well-being. Cells in hanging drops and embedded in matrigel formed multicellular aggregates but they were difficult to handle and propagate for further experiments. The most widely used methods: ultra-low attachment plate (ULA) and spheroid inducing media (SFDM) were not the most viable 3D model of RC-4B/C and GH3 cells that would be suitable for further experiments. Combining spheroid generation with matrigel scaffold H295R 3D models were viable for 7 days, RC-4B/C and GH3 3D models for 7–10 days. ULA and SFDM 3D models of PC-12 cells could be used for further experiments up to 4 days. Higher steroid production in 3D models compared to conventional monolayer culture was detected. Endocrine tumor cells require extracellular matrix as scaffold for viable 3D models that can be one reason behind the lack of the usage of endocrine 3D cultures. Our models help understanding the pathogenesis of endocrine tumors and revealing potential biomarkers and therapeutic targets. They could also serve as an excellent platform for preclinical drug test screening.
C1 [Krokker, Lilla] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Szabo, Borbala] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Nemeth, Kinga] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Tohati, Rebeka] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Sarkadi, Balazs] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Meszaros, Katalin] Hungarian Academy of Sciences and Semmelweis University, Hereditary Endocrine Tumors Research GroupBudapest, Hungary.
[Patocs, Attila] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Butz, Henriett] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
RP Butz, H (reprint author), Semmelweis University, Department of Laboratory Medicine, Budapest, Hungary.
EM butz.henriett@med.semmelweis-univ. hu
CR Ravi M, Ramesh A, and Pattabhi A. Contributions of 3D Cell Cultures for Cancer Research. J Cel Physiol, 2017, 232:2679–97., DOI 10.1002/jcp.25664
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Hallanger-Johnson JE. Systemic Therapy for Adrenocortical Carcinoma: a Review. AME Med J, 2020, 5:5., DOI 10.21037/amj.2020.01.07
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Mallet C, Feraud O, Ouengue-Mbele G, Gaillard I, Sappay N, Vittet D, et al. Differential Expression of VEGF Receptors in Adrenal Atrophy Induced by Dexamethasone: a Protective Role of ACTH. Am J Physiology- EndocrinologyMetab, 2003, 284:E156–E167., DOI 10.1152/ajpendo.00450. 2001
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 640676
EP 640685
DI 10.3389/pore.2021.640676
PG 10
ER
PT J
AU Lin, H
Zeng, W
Lei, Y
Chen, D
Nie, Z
AF Lin, Hua
Zeng, Weifeng
Lei, Yuhang
Chen, Desheng
Nie, Zhen
TI Tuftelin 1 (TUFT1) Promotes the Proliferation and Migration of Renal Cell Carcinoma via PI3K/AKT Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE renal cell carcinoma; tuftelin 1; proliferation; migration; signaling pathway
ID renal cell carcinoma; tuftelin 1; proliferation; migration; signaling pathway
AB Tuftelin 1 (TUFT1), a protein functioning distinctively in different tissues, is reported to be elevated in several types of cancers and the elevation of TUFT1 is correlated with unfavorable clinicopathologic characteristics and poor survival. However, the involvement of TUFT1 in renal cell carcinoma (RCC) remains unknown. In the current study, we investigated the role of TUFT1 in RCC and potential underlying mechanisms. RTPCR and Western blot analysis showed that both the mRNA and protein levels of TUFT1 were increased in primary RCC tissue and RCC cell lines. TUFT1 overexpression in RCC cells resulted in enhanced cell proliferation and migration while knockdown of TUFT1 by contrast decreased the growth and migration of the RCC cells, indicating TUFT1 expression is involved in RCC cell growth and migration. The involvement of TUFT1 in the epithelial-mesenchymal transition (EMT) of RCC cells was also determined by measuring the expression of EMT-related markers. Our data showed that TUFT1 overexpression promoted RCC cell EMT progression while knockdown of TUFT1 suppressed such process. Further signaling pathway inhibition assay revealed that TUFT1-induced RCC cell growth, migration and EMT was significantly suppressed by PI3K inhibitor, but not JNK or MEK inhibitors. In addition, TUFT1 overexpression enhanced the AKT phosphorylation, a key member of the PI3K signaling pathway, while PI3K inhibitor suppressed such process. Taken together, our study showed that TUFT1 expression was elevated in RCC and such elevation promoted the proliferation, migration and EMT of RCC cells in vitro, through PI3K/AKT signaling pathway. The findings of our current study imply that TUFT1 is involved in RCC tumorigenesis, and it may serve as a biomarker for RCC diagnosis and a potential target for RCC treatment.
C1 [Lin, Hua] Xiantao First People’s Hospital Affiliated to Yangtze University, Department of UrologyXiantao, China.
[Zeng, Weifeng] Xiantao First People’s Hospital Affiliated to Yangtze University, Department of UrologyXiantao, China.
[Lei, Yuhang] Xiantao First People’s Hospital Affiliated to Yangtze University, Department of UrologyXiantao, China.
[Chen, Desheng] Xiantao First People’s Hospital Affiliated to Yangtze University, Department of UrologyXiantao, China.
[Nie, Zhen] Xiantao First People’s Hospital Affiliated to Yangtze University, Department of UrologyXiantao, China.
RP Nie, Z (reprint author), Xiantao First People’s Hospital Affiliated to Yangtze University, Department of Urology, Xiantao, China.
EM n_zhen@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 640936
EP 640945
DI 10.3389/pore.2021.640936
PG 10
ER
PT J
AU Cai, M
Tan, R
Huang, Y
Chen, X
Kong, Q
Guo, K
Xu, M
AF Cai, Min
Tan, Rukeng
Huang, Yunyi
Chen, Xuanyi
Kong, Qingci
Guo, Kaixin
Xu, Meng
TI High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE oral squamous cell carcinoma; Tomm34; Immunohistochemistry; clinicopathology; bioinformatics
ID oral squamous cell carcinoma; Tomm34; Immunohistochemistry; clinicopathology; bioinformatics
AB Tomm34, as a member of the outer mitochondrial membrane proteins, is evenly distributed between the cytoplasmand the outer mitochondrialmembrane. It is up-regulated in a variety of tumors and correlates with poor prognosis. This study aimed to investigate expression of Tomm34 and its correlations with clinicopathology in oral squamous cell carcinoma (OSCC). Oncomine database and UALCAN database were utilized to predict the expression and prognosis values of Tomm34 in head and neck squamous cell carcinoma (HNSCC). By immunohistochemistry, a retrospective study was performed to verify the bioinformatics results to evaluate the Tomm34 expression and clinicopathological variables in both HPVpositive OSCC and HPV-negative OSCC. Immunohistochemistry of our cohort revealed that 48 cases fulfilled the Tomm34 high expression judgment criteria, and the overall positive rate was 60% (48/80), and 27 cases fulfilled the p16 expression judgment criteria (33.75%, 27/ 80). The high expression of Tomm34 was closely related with the TNM classification of OSCC (p < 0.01) and tumor size (p < 0.01) both in HPV-negative OSCC and HPV-positive OSCC, while related with lymph node metastasis (p = 0.001) in HPV-negative OSCC and drinking history (p = 0.044) in HPV-positive OSCC. In addition, the Kaplan-Meier curves indicated that higher level of Tomm34 was correlated with poorer overall survival (OS) and disease-free survival (DFS) in HPV-negativeOSCC (OS, p = 0.046; DFS, p = 0.020) but not in HPV-positive OSCC (OS, p = 0.824; DFS, p = 0.782). In conclusion, Tomm34 is highly expressed in OSCC and may be a useful factor to provide prognostic information, especially in HPV-negative OSCC group.
C1 [Cai, Min] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Tan, Rukeng] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Huang, Yunyi] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Chen, Xuanyi] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Kong, Qingci] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Guo, Kaixin] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
[Xu, Meng] Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of StomatologyGuangzhou, China.
RP Xu, M (reprint author), Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Hospital of Stomatology, Guangzhou, China.
EM xumeng23@mail.sysu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 641042
EP 641051
DI 10.3389/pore.2021.641042
PG 10
ER
PT J
AU Peeters, M
Geusens, J
Van der Cruyssen, F
Michaux, L
de Leval, L
Tousseyn, Th
Vandenberghe, P
Politis, C
AF Peeters, Maxime
Geusens, Joris
Van der Cruyssen, Frederic
Michaux, Lucienne
de Leval, Laurence
Tousseyn, Thomas
Vandenberghe, Peter
Politis, Constantinus
TI Case Report: Spontaneous Remission of an Infraorbital Follicular B-Cell Lymphoma: Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE follicular lymphoma; cheek; spontaneous remission; head and neck neoplasms; case reports
ID follicular lymphoma; cheek; spontaneous remission; head and neck neoplasms; case reports
AB Non-Hodgkin lymphomas comprise a heterogeneous group of malignancies, with a wide scope of clinical, radiological and histological presentations. In this paper, a case is presented of a 59-year-old white male with an infraorbital follicular B-cell lymphoma, which appeared as a painless mass in the left cheek. The lymphoma achieved spontaneous remission five and a half months after his diagnostic incision biopsy. The literature is reviewed, focusing on this rare site of presentation and spontaneous remission. In literature, only four cases have been reported with a follicular B-cell lymphoma of the cheek or infraorbital region, and only 26 cases of spontaneous remission of an extracranial non-Hodgkin lymphoma in the head and neck region have been described. To the authors’ best knowledge, this is the first time spontaneous remission of an infraorbital follicular lymphoma could be observed. The nature of the processes inducing spontaneous remission remains obscure. It is important to recognize this phenomenon as this might prevent unnecessary treatment.
C1 [Peeters, Maxime] University Hospitals Leuven, Department of Oral and Maxillofacial SurgeryLeuven, Belgium.
[Geusens, Joris] University Hospitals Leuven, Department of Oral and Maxillofacial SurgeryLeuven, Belgium.
[Van der Cruyssen, Frederic] University Hospitals Leuven, Department of Oral and Maxillofacial SurgeryLeuven, Belgium.
[Michaux, Lucienne] University Hospitals Leuven, Department of Human GeneticsLeuven, Belgium.
[de Leval, Laurence] Lausanne University Hospital (CHUV) and Lausanne University, Department of PathologyLausanne, Switzerland.
[Tousseyn, Thomas] University Hospitals Leuven, Department of PathologyLeuven, Belgium.
[Vandenberghe, Peter] University Hospitals Leuven, Department of HematologyLeuven, Belgium.
[Politis, Constantinus] University Hospitals Leuven, Department of Oral and Maxillofacial SurgeryLeuven, Belgium.
RP Peeters, M (reprint author), University Hospitals Leuven, Department of Oral and Maxillofacial Surgery, Leuven, Belgium.
EM maxime.peeters.mp1@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 642433
EP 642441
DI 10.3389/pore.2021.642433
PG 9
ER
PT J
AU Maros, M
Balla, P
Micsik, T
Sapi, Z
Szendroi, M
Wenz, H
Groden, Ch
Forsyth, R
Picci, P
Krenacs, T
AF Maros, E. Mate
Balla, Peter
Micsik, Tamas
Sapi, Zoltan
Szendroi, Miklos
Wenz, Holger
Groden, Christoph
Forsyth, G. Ramses
Picci, Piero
Krenacs, Tibor
TI Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE giant cell tumor of bone; giant cells; Ki-67; cyclin D1; p53; p21 (CDKN1A) WAF1; cyclin G1
ID giant cell tumor of bone; giant cells; Ki-67; cyclin D1; p53; p21 (CDKN1A) WAF1; cyclin G1
AB Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.
C1 [Maros, E. Mate] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Balla, Peter] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Wenz, Holger] University of Heidelberg, Medical Faculty Mannheim, Department of NeuroradiologyMannheim, Germany.
[Groden, Christoph] University of Heidelberg, Medical Faculty Mannheim, Department of NeuroradiologyMannheim, Germany.
[Forsyth, G. Ramses] University Ziekenhuis, Department of Anatomic Pathology and Experimental PathologyBrussels, Belgium.
[Picci, Piero] Istituti Ortopedici Rizzoli, Laboratorio di Ricerca OncologicaBologna, Italy.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Krenacs, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM krenacst@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 643146
EP 643156
DI 10.3389/pore.2021.643146
PG 11
ER
PT J
AU Zhang, Y
Zhou, B
Sun, J
He, Q
Zhao, Y
AF Zhang, Ye
Zhou, Bo
Sun, Jingjing
He, Qun
Zhao, Yujie
TI Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE B-cell acute lymphoblastic leukemia; GPSM1; ADCY6; RAPGEF3; JNK
ID B-cell acute lymphoblastic leukemia; GPSM1; ADCY6; RAPGEF3; JNK
AB B-cell acute lymphoblastic leukemia (B-ALL) is the common type of blood cancer. Although the remission rate has increased, the current treatment options for B-ALL are usually related to adverse reactions and recurrence, so it is necessary to find other treatment options. G protein signaling modulator 1 (GPSM1) is one of several factors that affect the basic activity of the G protein signaling system, but its role in B-ALL has not yet been clarified. In this study, we analyzed the expression of GPSM1 in the Oncomine database and found that the GPSM1 levels were higher in B-ALL cells than in peripheral blood mononuclear cells (PBMCs). Analyses of the Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that patients with high GPSM1 levels had shorter survival times than those with low levels. Additionally, gene set enrichment analysis (GSEA) suggested that GPSM1 was positively correlated with proliferation, G protein-coupled receptor (GPCR) ligand binding, Gαs signaling and calcium signaling pathways. In further experiments, GPSM1 was found to be highly expressed in Acute lymphoblastic leukemia (ALL) cell lines, and downregulation of GPSM1 inhibited proliferation and promoted cell cycle arrest and apoptosis in BALL-1 and Reh cells. Moreover, knockdown of GPSM1 suppressed ADCY6 and RAPGEF3 expression in BALL-1 and Reh cells. Furthermore, we reported that GPSM1 regulated JNK expression via ADCY6-RAPGEF3. The present study demonstrates that GPSM1 promotes tumor growth in BALL-1 and Reh cells by modulating ADCY6-RAPGEF3-JNK signaling.
C1 [Zhang, Ye] China Medical University, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of EducationShenyang, China.
[Zhou, Bo] China Medical University, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of EducationShenyang, China.
[Sun, Jingjing] China Medical University, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of EducationShenyang, China.
[He, Qun] China Medical University, School of Life Sciences, Department of BioinformaticsShenyang, China.
[Zhao, Yujie] China Medical University, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of EducationShenyang, China.
RP Zhao, Y (reprint author), China Medical University, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, Shenyang, China.
EM yjzhao_biocell@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 643376
EP 643386
DI 10.3389/pore.2021.643376
PG 11
ER
PT J
AU Szasz, R
Telek, B
Illes,
AF Szasz, Robert
Telek, Bela
Illes, Arpad
TI Fludarabine-Cyclophosphamide- Rituximab Treatment in Chronic Lymphocytic Leukemia, Focusing on Long Term Cytopenias Before and After the Era of Targeted Therapies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE treatment; chronic lymphocytic leukemia; fludarabine; cyclophosphamide; rituximab; cytopenia
ID treatment; chronic lymphocytic leukemia; fludarabine; cyclophosphamide; rituximab; cytopenia
AB The widespread application of fludarabine, cyclophosphamide, and rituximab combination is limited due to its toxicity, particularly the prolonged cytopenias. The study aimed to compare the prolonged cytopenias depending on fitness and report real-life data on dose reduction measures and efficacy. According to our database, 120 and 14 patients were treated with FCR between 2011 and 2015 and between 2016 and 2019. Out of the first cohort, 34 patients were treated in subsequent lines. The complete and partial remission rate after first-line treatment was 79%, 16% in the first cohort and 86%, 14% in the second cohort, respectively; and 47%, 35% after non first-line treatment. Based on today’s standards, only 37.5% of the patients were fit for FCR. The frequency of persistent cytopenia was 14%, and it was significantly associated with fitness (χ2 (1) = 6.001, p = 0.014 for all patients). The small number of FCR treated patients after 2016 shows how the availability of targeted therapies, mostly ibrutinib, in later lines changed the first-line choice. Recently, it is recommended first-line for fit patients with mutated IGHV and no TP53 aberrations. With this narrow indication, a decrease in the frequency of persistent cytopenias is predicted.
C1 [Szasz, Robert] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Telek, Bela] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Szasz, R (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM szaszr@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609742
EP 1609748
DI 10.3389/pore.2021.1609742
PG 7
ER
PT J
AU Huang, L
Li, Y
Du, J
Li, H
Lu, M
Wang, Y
Zhou, W
Wang, W
Wu, H
AF Huang, Liangliang
Li, Yujie
Du, Jun
Li, Heng
Lu, Mengmeng
Wang, Yuting
Zhou, Wenchao
Wang, Wei
Wu, Haibo
TI The Prognostic Value of Retraction Clefts in Chinese Invasive Breast Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; clinicopathological features; invasive breast carcinoma; retraction clefts; Chinese
ID prognosis; clinicopathological features; invasive breast carcinoma; retraction clefts; Chinese
AB Some studies reported the correlation between retraction clefts (RCs) and the clinicopathological features as well as prognosis in invasive breast carcinoma. However, limited number of investigations have been done and controversial results were reported. Larger population studies around the world might help to provide more accurate and comprehensive information. Thus, we examined the correlation between the extent of RCs and the clinicopathological features as well as the prognosis in 541 invasive breast carcinoma samples from Central China in this study. The statistical analyses were performed with the Pearson χ2 tests and univariate Cox proportional hazards regression assays. Compared with other studies, lower RCs occurrence rate (15.5%) was observed in Chinese breast cancer patients and opposite association between the presence of RCs and lymph nodes metastasis was identified, in which both progression free survival (PFS) and overall survival (OS) were improved with the presence of RCs in our study. Besides, despite some statistically significant associations between RCs and molecular subtypes, RCs and estrogen receptor status, the results were largely depending on the stratification methods. Generally, no convincing association was detected between the extent of RCs and the clinicopathological features or prognosis. In sum, the extent of RCs showed limited value as a prognostic predictor in invasive breast carcinoma patients from Central China.
C1 [Huang, Liangliang] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Li, Yujie] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Du, Jun] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Li, Heng] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Lu, Mengmeng] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Wang, Yuting] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Zhou, Wenchao] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Wang, Wei] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
[Wu, Haibo] University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of PathologyHefei, China.
RP Wang, W (reprint author), University of Science and Technology of China, Division of Life sciences and Medicine, The First Affiliated Hospital of USTC, Department of Pathology, Hefei, China.
EM weiwang@hmfl.ac.cn
CR Harbeck N, and Gnant M. Breast cancer. The Lancet, 2017, 389:1134–50., DOI 10.1016/S0140-6736(16)31891-8
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609743
EP 1609750
DI 10.3389/pore.2021.1609743
PG 8
ER
PT J
AU Au, KY
Lo, ChLR
AF Au, Kwan-Yung
Lo, Cheuk-Lam Regina
TI An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE liver; β-catenin; CD8; tregs; metastatic carcinoma
ID liver; β-catenin; CD8; tregs; metastatic carcinoma
AB The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma. The results showed that colorectal primary constituted the largest proportion of metastatic carcinoma showing β-catenin overexpression. Intra-tumoral CD8 count was lower and FoxP3 count was higher when compared with the non-tumoral liver parenchyma. β-catenin overexpression was associated with a lower CD8 count in the tumor region (p = 0.003). In summary, our findings are in support of an altered immune tumor microenvironment vs. the non-tumor liver tissues in the metastatic site. Suppression of CD8 count was associated with activated Wnt/β-catenin signaling in the metastatic tumor.
C1 [Au, Kwan-Yung] The University of Hong Kong, Department of PathologyPok Fu Lam, Hong Kong.
[Lo, Cheuk-Lam Regina] The University of Hong Kong, Department of PathologyPok Fu Lam, Hong Kong.
RP Lo, ChLR (reprint author), The University of Hong Kong, Department of Pathology, Pok Fu Lam, Hong Kong.
EM reginalo@pathology.hku.hk
CR Hinshaw DC, and Shevde LA. The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res, 2019, 79(18):4557–66., DOI 10. 1158/0008-5472.CAN-18-3962[published Online First: Epub Date]
Luke JJ, Bao R, Sweis RF, Spranger S, and Gajewski TF. WNT/β-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers. Clin Cancer Res, 2019, 25(10):3074–83., DOI 10.1158/1078-0432. CCR-18-1942[published Online First: Epub Date]
Galluzzi L, Spranger S, Fuchs E, and Lopez-Soto A. WNT Signaling in Cancer Immunosurveillance. Trends Cel Biol, 2019, 29(1):44–65., DOI 10.1016/j.tcb. 2018.08.005[published Online First: Epub Date]
Li X, Xiang Y, Li F, Yin C, Li B, and Ke X. WNT/β-Catenin Signaling Pathway Regulating T Cell-Inflammation in the Tumor Microenvironment. Front Immunol, 2019, 10:2293., DOI 10.3389/fimmu.2019.02293[published Online First: Epub Date]
White BD, Chien AJ, and Dawson DW. Dysregulation of Wnt/β-Catenin Signaling in Gastrointestinal Cancers. Gastroenterol, 2012, 142(2):219–32., DOI 10.1053/j.gastro.2011.12.001[published Online First: Epub Date]
Leung CO-N, MakW-N, Kai AK-L, Chan K-S, Lee TK-W, Ng IO-L, et al.Sox9 Confers Stemness Properties in Hepatocellular Carcinoma through Frizzled-7 Mediated Wnt/β-Catenin Signaling. Oncotarget, 2016, 7(20):29371–86., DOI 10.18632/oncotarget.8835[published Online First: Epub Date]
Lo RC-L, Leung CO-N, Chan KK-S, Ho DW-H, Wong C-M, Lee TK-W, et al.Cripto-1 Contributes to Stemness in Hepatocellular Carcinoma by Stabilizing Dishevelled-3 and Activating Wnt/β-Catenin Pathway. Cell Death Differ, 2018, 25(8):1426–41., DOI 10.1038/s41418-018-0059-x [published Online First: Epub Date]
Bugter JM, Fenderico N, and Maurice MM. Mutations and Mechanisms of WNT Pathway Tumour Suppressors in Cancer. Nat Rev Cancer, 2020, 21: 5–21., DOI 10.1038/s41568-020-00307-z[published Online First: Epub Date]
Liu Y, and Cao X. Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell, 2016, 30(5):668–81., DOI 10.1016/j.ccell.2016.09.011[published Online First: Epub Date]
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609752
EP 1609757
DI 10.3389/pore.2021.1609752
PG 6
ER
PT J
AU Xing, AY
Wang, B
Li, YH
Chen, X
Wang, YW
Liu, HT
Gao, P
AF Xing, Ai-Yan
Wang, Bin
Li, Yu-Hong
Chen, Xu
Wang, Ya-Wen
Liu, Hai-Ting
Gao, Peng
TI Identification of miRNA Signature in Breast Cancer to Predict Neoadjuvant Chemotherapy Response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; microarray; miRNA signature; neoadjuvant chemotherapy; drug resistance
ID breast cancer; microarray; miRNA signature; neoadjuvant chemotherapy; drug resistance
AB Chemotherapy failure causes high breast cancer recurrence and poor patient prognosis. Thus, we studied a cohort of novel biomarkers to predict chemotherapeutic response in breast cancer. In this study, miRNA expression profiling was performed on 10 breast cancer punctured specimens sensitive to chemotherapy (MP grade 4, 5) and 10 chemotherapy resistant (MP grade 1). Differentially expressed miRNAs were verified by qRT-PCR in 60 initial samples, 59 validated samples and 71 independent samples. A miRNA signature was generated using a Logistic regression model. A receiver operating characteristic (ROC) test was used to assess specificity and sensitivity of single miRNA and miRNA signature. Target genes regulated by miRNAs and their involved signaling pathways were analyzed using GO enrichment and KEGG software. MiRNAs expression were separately compared with ER, PR, HER2 immunohistochemical staining and different drugs. qRT-PCR showed that the high expression of miR-23a-3p, miR-200c-3p, miR-214-3p and the low expression of miR-451a and miR-638 were closely related to chemoresistance. According to the formula for calculating the drug resistance risk, patients in the high-risk group were more likely to develop chemotherapy resistance than the low-risk group. Bioinformatics analysis showed that 5 miRNAs and target genes are mainly involved in p53, ubiquitin-mediated proteolysis, mTOR, Wnt, cells skeletal protein regulation, cell adhesion and ErbB signaling pathways. miR-451a expression was associated with ER, HER-2 status and anthracyclines. A miRNA signature of chemotherapeutic response may be clinically valuable for improving current chemotherapy regimens of individual treatment for patients with breast cancer.
C1 [Xing, Ai-Yan] Shandong Univeristy, School of Medicine, Department of PathologyJinan, China.
[Wang, Bin] The First Affiliated Hospital of Shandong First Medical University, Department of SurgeryJinan, China.
[Li, Yu-Hong] Liaocheng People’s Hospital, Department of PathologyLiaocheng, China.
[Chen, Xu] Shandong University, Qilu Hospital, Department of PathologyJinan, China.
[Wang, Ya-Wen] Shandong Univeristy, QiLu Hospital, Department of Breast SurgeryJinan, China.
[Liu, Hai-Ting] Shandong Univeristy, School of Medicine, Department of PathologyJinan, China.
[Gao, Peng] Shandong Univeristy, School of Medicine, Department of PathologyJinan, China.
RP Gao, P (reprint author), Shandong Univeristy, School of Medicine, Department of Pathology, Jinan, China.
EM gaopeng@sdu.edu.cn
CR Siegel RL, Miller KD, and Jemal A Cancer statistics, 2016. CA: A Cancer J Clinicians, 2016, 66:7–30., DOI 10.3322/caac.21332
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609753
EP 1609763
DI 10.3389/pore.2021.1609753
PG 11
ER
PT J
AU Hrudka, J
Prouzova, Z
Mydlikova, K
Jedlickova, K
Holesta, M
Whitley, A
Havluj, L
AF Hrudka, Jan
Prouzova, Zuzana
Mydlikova, Katarina
Jedlickova, Kristina
Holesta, Michal
Whitley, Adam
Havluj, Lukas
TI FOXF1 as an Immunohistochemical Marker of Hilar Cholangiocarcinoma or Metastatic Pancreatic Ductal Adenocarcinoma. Single Institution Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE intrahepatic cholangiocarcinoma; cholangiocarcinoma; Foxf1; peripheral; hilar; extrahepatic
ID intrahepatic cholangiocarcinoma; cholangiocarcinoma; Foxf1; peripheral; hilar; extrahepatic
AB Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/ intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.
C1 [Hrudka, Jan] Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of PathologyPrague, Czech Republic.
[Prouzova, Zuzana] Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of PathologyPrague, Czech Republic.
[Mydlikova, Katarina] Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of PathologyPrague, Czech Republic.
[Jedlickova, Kristina] Institute for Clinical and Experimental Medicine, Clinical and Transplant Pathology CentrePrague, Czech Republic.
[Holesta, Michal] Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Department of RadiodiagnosticsPrague, Czech Republic.
[Whitley, Adam] Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Department of General SurgeryPrague, Czech Republic.
[Havluj, Lukas] Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Department of General SurgeryPrague, Czech Republic.
RP Hrudka, J (reprint author), Charles University, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, The Fingerland Department of Pathology, Prague, Czech Republic.
EM jan.hrudka@fnkv.cz
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609756
EP 1609764
DI 10.3389/pore.2021.1609756
PG 9
ER
PT J
AU Wang, L
Liu, D
Wei, J
Yuan, L
Zhao, Sh
Huang, Y
Ma, J
Yang, Z
AF Wang, Linlin
Liu, Dan
Wei, Jun
Yuan, Liwei
Zhao, Shiyun
Huang, Yani
Ma, Jingwen
Yang, Zhijuan
TI MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE molecular biology; miRNA-543; MAPK1; wnt/β-catenin; endometrial stromal cell
ID molecular biology; miRNA-543; MAPK1; wnt/β-catenin; endometrial stromal cell
AB Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factorbeta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3′ untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
C1 [Wang, Linlin] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Liu, Dan] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Wei, Jun] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Yuan, Liwei] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Zhao, Shiyun] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Huang, Yani] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Ma, Jingwen] General Hospital of Ningxia Medical University, Department of GynecologyYinchuan, China.
[Yang, Zhijuan] General Hospital of Ningxia Medical University, Department of GynecologyYinchuan, China.
RP Wei, J (reprint author), Ningxia Medical University, College of Clinical Medicine, Yinchuan, China.
EM 13895418876@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609761
EP 1609771
DI 10.3389/pore.2021.1609761
PG 11
ER
PT J
AU Wu, B
Tang, X
Ke, H
Zhou, Q
Zhou, Z
Tang, Sh
Ke, R
AF Wu, Baojin
Tang, Xinjie
Ke, Honglin
Zhou, Qiong
Zhou, Zhaoping
Tang, Shao
Ke, Ronghu
TI Gene Regulation Network of Prognostic Biomarker YAP1 in Human Cancers: An Integrated Bioinformatics Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; prognosis; YAP1; bioinformatic; mitochondrial
ID cancer; prognosis; YAP1; bioinformatic; mitochondrial
AB Background: Yes-associated protein 1 (YAP1) is the main downstream effector of the Hippo signaling pathway, which is involved in tumorigenesis. This study aimed to comprehensively understand the prognostic performances of YAP1 expression and its potential mechanism in pan-cancers by mining databases. Methods: The YAP1 expression was evaluated by the Oncomine database and GEPIA tool. The clinical significance of YAP1 expression was analyzed by the UALCAN, GEPIA, and DriverDBv3 database. Then, the co-expressed genes with YAP1 were screened by the LinkedOmics, and annotated by the Metascape and DAVID database. Additionally, by the MitoMiner 4.0 v tool, the YAP1 co-expressed genes were screened to obtain the YAP1-associated mitochondrial genes that were further enriched by DAVID and analyzed by MCODE for the hub genes. Results: YAP1 was differentially expressed in human cancers. Higher YAP1 expression was significantly associated with poorer overall survival and disease-free survival in adrenocortical carcinoma (ACC), brain Lower Grade Glioma (LGG), and pancreatic adenocarcinoma (PAAD). The LinkedOmics analysis revealed 923 co-expressed genes with YAP1 in adrenocortical carcinoma, LGG and PAAD. The 923 genes mainly participated in mitochondrial functions including mitochondrial gene expression and mitochondrial respiratory chain complex I assembly. Of the 923 genes, 112 mitochondrial genes were identified by MitoMiner 4.0 v and significantly enriched in oxidative phosphorylation. The MCODE analysis identified three hub genes including CHCHD1, IDH3G and NDUFAF5. Conclusion: Our findings showed that the YAP1 overexpression could be a biomarker for poor prognosis in ACC, LGG and PAAD. Specifically, the YAP1 co-expression genes were mainly involved in the regulation of mitochondrial function especially in oxidative phosphorylation. Thus, our findings provided evidence of the carcinogenesis of YAP1 in human cancers and new insights into the mechanisms underlying the role of YAP1 in mitochondrial dysregulation.
C1 [Wu, Baojin] Fudan University, Huashan Hospital, Department of Plastic SurgeryShanghai, China.
[Tang, Xinjie] Fudan University, Huashan Hospital, Department of Plastic SurgeryShanghai, China.
[Ke, Honglin] Fudan University, Huashan Hospital, Department of EmergencyShanghai, China.
[Zhou, Qiong] Florida State University, Department of StatisticsTallahassee, FL, USA.
[Zhou, Zhaoping] Fudan University, Huashan Hospital, Department of Plastic SurgeryShanghai, China.
[Tang, Shao] Florida State University, Department of StatisticsTallahassee, FL, USA.
[Ke, Ronghu] Fudan University, Huashan Hospital, Department of Plastic SurgeryShanghai, China.
RP Ke, R (reprint author), Fudan University, Huashan Hospital, Department of Plastic Surgery, Shanghai, China.
EM ronghuke@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609768
EP 1609780
DI 10.3389/pore.2021.1609768
PG 13
ER
PT J
AU Bogos, K
Kiss, Z
Kerpel Fronius, A
Temesi, G
Elek, J
Madurka, I
Cselko, Zs
Csanyi, P
Abonyi-Toth, Zs
Rokszin, Gy
Barcza, Zs
Moldvay, J
AF Bogos, Krisztina
Kiss, Zoltan
Kerpel Fronius, Anna
Temesi, Gabriella
Elek, Jen}o
Madurka, Ildiko
Cselko, Zsuzsanna
Csanyi, Peter
Abonyi-Toth, Zsolt
Rokszin, Gyorgy
Barcza, Zsofia
Moldvay, Judit
TI Different Trends in Excess Mortality in a Central European Country Compared to Main European Regions in the Year of the COVID-19 Pandemic (2020): a Hungarian Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hungary; covid-19 pandemic; excess mortality; cumulative death; age-standardized mortality rate
ID Hungary; covid-19 pandemic; excess mortality; cumulative death; age-standardized mortality rate
AB Objective: This study examined cumulative excess mortality in European countries in the year of the Covid-19 pandemic and characterized the dynamics of the pandemic in different countries, focusing on Hungary and the Central and Eastern European region. Methods: Age-standardized cumulative excess mortality was calculated based on weekly mortality data from the EUROSTAT database, and was compared between 2020 and the 2016–2019 reference period in European countries. Results: Cumulate weekly excess mortality in Hungary was in the negative range until week 44. By week 52, it reached 9,998 excess deaths, corresponding to 7.73% cumulative excess mortality vs. 2016–2019 (p-value = 0.030 vs. 2016–2019). In Q1, only Spain and Italy reported excess mortality compared to the reference period. Significant increases in excess mortality were detected between weeks 13 and 26 in Spain, United Kingdom, Belgium, Netherland and Sweden. Romania and Portugal showed the largest increases in agestandardized cumulative excess mortality in the Q3. The majority of Central and Eastern European countries experienced an outstandingly high impact of the pandemic in Q4 in terms of excess deaths. Hungary ranked 11th in cumulative excess mortality based on the latest available data of from the EUROSTAT database. Conclusion: Hungary experienced a mortality deficit in the first half of 2020 compared to previous years, which was followed by an increase in mortality during the second wave of the COVID-19 pandemic, reaching 7.7% cumulative excess mortality by the end of 2020. The excess was lower than in neighboring countries with similar dynamics of the pandemic.
C1 [Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Kiss, Zoltan] University of Pecs, 2nd Department of Medicine and Nephrological CenterPecs, Hungary.
[Kerpel Fronius, Anna] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Temesi, Gabriella] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Elek, Jen}o] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Madurka, Ildiko] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Cselko, Zsuzsanna] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Csanyi, Peter] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Barcza, Zsofia] Syntesia LtdBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Semmelweis University, Ist Department of PulmonologyBudapest, Hungary.
RP Kiss, Z (reprint author), University of Pecs, 2nd Department of Medicine and Nephrological Center, Pecs, Hungary.
EM dr.zoltan.kiss.privat@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609774
EP 1609782
DI 10.3389/pore.2021.1609774
PG 9
ER
PT J
AU Qin, J
Xie, F
Li, Ch
Han, N
Lu, H
AF Qin, Jing
Xie, Fajun
Li, Chenghui
Han, Na
Lu, Hongyang
TI MYCL1 Amplification and Expression of L-Myc and c-Myc in Surgically Resected Small-Cell Lung Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; small-cell lung carcinoma; C-MYC; fluorescence in situ hybridization; MYCL1 amplification; L-myc
ID immunohistochemistry; small-cell lung carcinoma; C-MYC; fluorescence in situ hybridization; MYCL1 amplification; L-myc
AB Purpose: The Myc family, especially C-MYC and MYCL1, has been found involved in small-cell lung carcinoma (SCLC). Identification of the frequency of C-MYC and MYCL1 expression among SCLC patients may help to identify potential targets for therapeutic intervention. Our aim was to detect MYCL1 amplification, L-Myc and c-Myc expression, and investigate clinicopathological characteristics and survival status in patients with surgically resected SCLC. Methods: MYCL1 amplification was detected using fluorescence in situ hybridization (FISH), while L-Myc and c-Myc protein expressions were determined using immunohistochemistry (IHC) in the primary tumors of 46 resected SCLC patients. Results: Among the 46 evaluated specimens, MYCL1 amplification was identified in 3/46 cases (6.5%). One of the positive cases was MYCL1 gene amplification combined with fusion. 3/46 (6.5%) was positive for L-myc protein expression, and 4/46 (8.7%) was positive for c-Myc protein expression. Conclusion: Our study firstly multidimensional explored the expression of MYCL1 amplification, L-Myc and c-Myc protein and investigated clinicopathological characteristics and survival status in patients with surgically resected SCLC, which makes a contribution to subsequent research and therapeutic strategies.
C1 [Qin, Jing] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical OncologyHangzhou, China.
[Xie, Fajun] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical OncologyHangzhou, China.
[Li, Chenghui] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical OncologyHangzhou, China.
[Han, Na] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical OncologyHangzhou, China.
[Lu, Hongyang] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical OncologyHangzhou, China.
RP Lu, H (reprint author), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Thoracic Medical Oncology, Hangzhou, China.
EM luhy@zjcc.org.cn
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Sos ML, Dietlein F, Peifer M, Schottle J, Balke-Want H, Muller C, et al. A Framework for Identification of Actionable Cancer Genome Dependencies in Small Cell Lung Cancer. Proc Natl Acad Sci, 2012, 109(42):17034–9., DOI 10.1073/pnas.1207310109
Melichar B, Adenis A, Lockhart AC, Bennouna J, Dees EC, Kayaleh O, et al. Safety and Activity of Alisertib, an Investigational aurora Kinase A Inhibitor, in Patients with Breast Cancer, Small-Cell Lung Cancer, Nonsmall- cell Lung Cancer, Head and Neck Squamous-Cell Carcinoma, and Gastro-Oesophageal Adenocarcinoma: a Five-Arm Phase 2 studyThe Lancet. Lancet Oncol, 2015, 16(4):395–405., DOI 10.1016/S1470-2045(15, 70051-3
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609775
EP 1609782
DI 10.3389/pore.2021.1609775
PG 8
ER
PT J
AU Kurdi, M
Butt, ShN
Baeesa, S
Alghamdi, B
Maghrabi, Y
Bardeesi, A
Saeedi, R
Al-Sinani, T
Alghanmi, N
Bari, M
Samkari, A
Lary, A
AF Kurdi, Maher
Butt, Shafique Nadeem
Baeesa, Saleh
Alghamdi, Badrah
Maghrabi, Yazid
Bardeesi, Anas
Saeedi, Rothaina
Al-Sinani, Taghreed
Alghanmi, Najla
Bari, O. Mohammed
Samkari, Alaa
Lary, I. Ahmed
TI The Impact of IDH1 Mutation and MGMT Promoter Methylation on Recurrence-Free Interval in Glioblastoma Patients Treated With Radiotherapy and Chemotherapeutic Agents
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glioblastoma; chemotherapy; IDH1 mutation; MGMT promoter methylation; radiotherapy
ID glioblastoma; chemotherapy; IDH1 mutation; MGMT promoter methylation; radiotherapy
AB The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation andO6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalitiesmay not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.
C1 [Kurdi, Maher] King Abdulaziz University, Faculty of Medicine in Rabigh, Department of PathologyJeddah, Saudi Arabia.
[Butt, Shafique Nadeem] King Abdulaziz University, Faculty of Medicine in Rabigh, Department of Family and Community MedicineJeddah, Saudi Arabia.
[Baeesa, Saleh] King Abdulaziz University, Faculty of Medicine in Rabigh, Division of NeurosurgeryJeddah, Saudi Arabia.
[Alghamdi, Badrah] King Abdulaziz University, Faculty of Medicine in Rabigh, Department of PhysiologyJeddah, Saudi Arabia.
[Maghrabi, Yazid] King Faisal Specialist Hospital, Department of NeuroscienceJeddah, Saudi Arabia.
[Bardeesi, Anas] King Faisal Specialist Hospital, Department of NeuroscienceJeddah, Saudi Arabia.
[Saeedi, Rothaina] King Abdulaziz University, Faculty of Medicine in Rabigh, Division of NeurosurgeryJeddah, Saudi Arabia.
[Al-Sinani, Taghreed] King Fahad General Hospital, Department of Surgery, Division of NeurosurgeryJeddah, Saudi Arabia.
[Alghanmi, Najla] King Abdulaziz University Hospital, Department of PathologyJeddah, Saudi Arabia.
[Bari, O. Mohammed] King Abdulaziz University Hospital, Department of PathologyJeddah, Saudi Arabia.
[Samkari, Alaa] King Abdulaziz University, Department of PathologyJeddah, Saudi Arabia.
[Lary, I. Ahmed] King Abdulaziz Medical City, Department of Surgery, Section of NeurosurgeryJeddah, Saudi Arabia.
RP Kurdi, M (reprint author), King Abdulaziz University, Faculty of Medicine in Rabigh, Department of Pathology, Jeddah, Saudi Arabia.
EM Ahkurdi@kau.edu.sa
CR Louis DN, Ohgaki H, Wiestler OD, and Cavenee WK. World Health Organization Histiological Classification of Tumours of the Central Nervous System. France: International Agency for Research on Cancer, 2016).
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Stupp R, Hegi ME, Mason WP, Van den Bent MJ, Taphoorn MJB, Janzer RC, et al., 2009, Effects of radiotherapy with concomitant and adjuvant temozolamide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–66., DOI 10.1016/s1470-2045(09)70025-7
Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol, 2009, 118:469–74., DOI 10.1007/s00401-009-0561-9
Capper D, WeiA¨ Yert S, Balss JR, Habel A, Meyer J, Jager D, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol, 2010, 20:245–54., DOI 10.1111/j.1750-3639. 2009.00352.x
Nobusawa S, Watanabe T, Kleihues P, and Ohgaki H. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res, 2009, 15(19):6002–7., DOI 10.1158/1078-0432.ccr-09-0715
Pegg AE. Repair of O6-alkylguanine by alkyltransferases. Mutat Research/ Reviews Mutat Res, 2000, 462:83–100., DOI 10.1016/s1383-5742(00)00017-x
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Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMTGene silencing and benefit from temozolomide in glioblastoma. N Engl J Med, 2005, 352:997–1003., DOI 10.1056/nejmoa043331
Dunn J, Baborie A, Alam F, Joyce K, Moxham M, Sibson R, et al. Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer, 2009, 101:124–31., DOI 10.1038/ sj.bjc.6605127
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Costa BM, Caeiro C, Guimaraes I, Martinho O, Jaraquemada T, Augusto I, et al. Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study. Oncol Rep, 2010, 23:1655–62., DOI 10.3892/or_00000808
Park C-K, Park S-H, Lee S-H, Kim C-Y, Kim D-W, Paek SH, et al. Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin. Neuropathology, 2009, 29:443–9., DOI 10.1111/j.1440-1789.2008.00998.x
Millward CP, Brodbelt AR, Haylock B, Zakaria R, Baborie A, Crooks D, et al. The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy. Acta Neurochir, 2016, 158:1943–53., DOI 10.1007/s00701-016-2928-8
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Panagopoulos I, Gorunova L, Leske H, Niehusmann P, Johannessen LE, Staurseth J, et al. Pyrosequencing Analysis of MGMT promoter methylation in meningioma. Cancer Genomics Proteomics, 2018, 15: 379–85., DOI 10.21873/cgp.20096
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Alassiri AH, Alkhaibary A, Al-Sarheed S, Alsufani F, Alharbi M, Alkhani A, et al. O 6 -methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma. Ann Saudi Med, 2019, 39(6):410–6., DOI 10.5144/ 0256-4947.2019.410
Pandith AA, Qasim I, Baba SM, Koul A, Zahoor W, Afroz D, et al. Favorable role of IDH1/2 mutations aided with MGMT promoter gene methylation in the outcome of patients with malignant glioma. Future Sci OA, 2020, 7(3): FSO663., DOI 10.2144/fsoa-2020-0057
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609778
EP 1609786
DI 10.3389/pore.2021.1609778
PG 9
ER
PT J
AU Boer, K
Kahan, Zs
Landherr, L
Cs}oszi, T
Mahr, K
Ruzsa,
Horvath, Zs
Budai, B
Rubovszky, G
AF Boer, Katalin
Kahan, Zsuzsanna
Landherr, Laszlo
Cs}oszi, Tibor
Mahr, Karoly
Ruzsa, Agnes
Horvath, Zsolt
Budai, Barna
Rubovszky, Gabor
TI Pathologic Complete Response Rates After Neoadjuvant Pertuzumab and Trastuzumab with Chemotherapy in Early Stage HER2-Positive Breast Cancer - Increasing Rates of Breast Conserving Surgery: A Real-World Experience
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE early breast cancer; HER2+; neoadjuvant systemic therapy; pathological complete response; breastconserving surgery; neutrophil-to-lymphocyte ratio
ID early breast cancer; HER2+; neoadjuvant systemic therapy; pathological complete response; breastconserving surgery; neutrophil-to-lymphocyte ratio
AB Purpose: The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data. Methods: This was a multicentre, retrospective, observational study in patients with stage II and III HER2+ early breast cancer who received pertuzumab and trastuzumab-based NST. Data were collected from patients’ medical records. Results: Eighty-two patients were included in the study treated in 8 cancer centers in Hungary between March 2015 and January 2020. The study included women with a median age of 50.3 years. The majority of the patients (95%) received a sequence of anthracycline-based chemotherapy followed by docetaxel. pCR was achieved in 54% of the cases. As a result of NST a significant increase of conservative breast surgeries (33% vs. 3.6% planned, p = 0.0001) was observed. Ki67 expression and neutrophil-tolymphocyte ratio (NLR) significantly predicted pCR. None of the variables were independent predictors of DFS. Conclusion: The pCR rate achieved in our study demonstrates the reproducibility of trial data in a real-world population. The rate of breast-conserving surgery was significantly increased.
C1 [Boer, Katalin] St. Margit Hospital, Clinical Oncology DepartmentBudapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Landherr, Laszlo] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Cs}oszi, Tibor] Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz, Klinikai OnkologiaSzolnok, Hungary.
[Mahr, Karoly] Zala Megyei Szent Rafael Korhaz, OnkologiaZalaegerszeg, Hungary.
[Ruzsa, Agnes] Somogy County Kaposi Mor Hospital, Department of OncologyKaposvar, Hungary.
[Horvath, Zsolt] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Budai, Barna] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Rubovszky, Gabor] Semmelweis University, Department of OncologyBudapest, Hungary.
RP Rubovszky, G (reprint author), Semmelweis University, Department of Oncology, Budapest, Hungary.
EM garub@oncol.hu
CR Early Breast Cancer Trialists’ Collaborative Group, EBCTCG). Long-term Outcomes for Neoadjuvant versus Adjuvant Chemotherapy in Early Breast Cancer: Meta-Analysis of Individual Patient Data from Ten Randomised Trials. Lancet Oncol, 2018, 19(1):27–39., DOI 10.1016/S1470-2045(17, 30777-5
Cain H, Macpherson IR, Beresford M, Pinder SE, Pong J, and Dixon JM. Neoadjuvant Therapy in Early Breast Cancer: Treatment Considerations and Common Debates in Practice. Clin Oncol, 2017, 29(10):642–52., DOI 10.1016/j. clon.2017.06.003
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological Complete Response and Long-Term Clinical Benefit in Breast Cancer: the CTNeoBC Pooled Analysis. Lancet, 2014, 384(9938):164–72., DOI 10.1016/S0140-6736(13)62422-8
Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early Breast Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol, 2019, 30(8):1194–220., DOI 10.1093/ annonc/mdz173
Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the Benefits of Therapy for Early-Stage Breast Cancer: the St. Gallen International Consensus Guidelines for the Primary Therapy of Early Breast Cancer 2019. Ann Oncol, 2019, 30(10):1541–57., DOI 10.1093/annonc/ mdz235
Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly Higher Pathologic Complete Remission Rate after Neoadjuvant Therapy with Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2- positive Operable Breast Cancer. J Clin Oncol, 2005, 23(16):3676–85., DOI 10. 1200/JCO.2005.07.032
Gianni L, EiermannW, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant Chemotherapy with Trastuzumab Followed by Adjuvant Trastuzumab versus Neoadjuvant Chemotherapy Alone, in Patients with HER2-Positive Locally Advanced Breast Cancer, The NOAH Trial): a Randomised Controlled Superiority Trial with a Parallel HER2-Negative Cohort. Lancet, 2010, 375(9712):377–84., DOI 10.1016/S0140-6736(09, 61964-4
Gianni L, EiermannW, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, et al. Neoadjuvant and Adjuvant Trastuzumab in Patients with HER2-Positive Locally Advanced Breast Cancer, NOAH): Follow-Up of a Randomised Controlled Superiority Trial with a Parallel HER2-Negative Cohort. Lancet Oncol, 2014, 15(6):640–7., DOI 10.1016/S1470-2045(14)70080-4
Gianni L, Pienkowski T, ImY-H, Roman L, Tseng L-M, Liu M-C, et al. Efficacy and Safety of Neoadjuvant Pertuzumab and Trastuzumab in Women with Locally Advanced, Inflammatory, or Early HER2-Positive Breast Cancer, NeoSphere): a Randomised Multicentre, Open-Label, Phase 2 Trial. Lancet Oncol, 2012, 13(1):25–32., DOI 10.1016/S1470-2045(11)70336-9
Gianni L, Pienkowski T, Im Y-H, Tseng L-M, Liu M-C, Lluch A, et al. 5-year Analysis of Neoadjuvant Pertuzumab and Trastuzumab in Patients with Locally Advanced, Inflammatory, or Early-Stage HER2-Positive Breast Cancer, NeoSphere): a Multicentre, Open-Label, Phase 2 Randomised Trial. Lancet Oncol, 2016, 17(6):791–800., DOI 10.1016/S1470-2045(16, 00163-7
Blumenthal GM, Scher NS, Cortazar P, Chattopadhyay S, Tang S, Song P, et al. First FDA Approval of Dual Anti-HER2 Regimen: Pertuzumab in Combination with Trastuzumab and Docetaxel for HER2-Positive Metastatic Breast Cancer. Clin Cancer Res, 2013, 19(18):4911–6., DOI 10. 1158/1078-0432.CCR-13-1212
Horvath Z, Boer K, Dank M, Zs K, Kocsis J, Kover E, et al. [Systemic Therapy of Breast Cancer: Practice Guideline]. Magy Onkol, 2016, 60(3):241–57.
Beitsch P, Whitworth P, Baron P, Rotkis MC, Mislowsky AM, Richards PD, et al. Pertuzumab/trastuzumab/CT versus Trastuzumab/CT Therapy for HER2+ Breast Cancer: Results from the Prospective Neoadjuvant Breast Registry Symphony Trial, NBRST). Ann Surg Oncol, 2017, 24:2539–46., DOI 10.1245/s10434-017-5863-x
Fasching PA, Hartkopf AD, Gass P, Haberle L, Akpolat-Basci L, Hein A, et al. Efficacy of Neoadjuvant Pertuzumab in Addition to Chemotherapy and Trastuzumab in Routine Clinical Treatment of Patients with Primary Breast Cancer: a Multicentric Analysis. Breast Cancer Res Treat, 2019, 173(2):319–28., DOI 10.1007/s10549-018-5008-3
Samiei S, van Nijnatten TJA, de Munck L, Keymeulen KBMI, Simons JM, Kooreman LFS, et al. Correlation between Pathologic Complete Response in the Breast and Absence of Axillary Lymph NodeMetastases after Neoadjuvant Systemic Therapy. Ann Surg, 2020, 271(3):574–80., DOI 10.1097/SLA. 0000000000003126
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab Plus Trastuzumab in Combination with Standard Neoadjuvant Anthracycline- Containing and Anthracycline-free Chemotherapy Regimens in Patients with HER2-Positive Early Breast Cancer: a Randomized Phase II Cardiac Safety Study, TRYPHAENA). Ann Oncol, 2013, 24:2278–84., DOI 10.1093/annonc/ mdt182
Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang C-S, Thompson AM, et al. Neoadjuvant Trastuzumab, Pertuzumab, and Chemotherapy versus Trastuzumab Emtansine Plus Pertuzumab in Patients with HER2- Positive Breast Cancer, KRISTINE): a Randomised, Open-Label, Multicentre, Phase 3 Trial. Lancet Oncol, 2018, 19:115–26., DOI 10.1016/ S1470-2045(17)30716-7
Ishii K, Morii N, and Yamashiro H. Pertuzumab in the Treatment of HER2-Positive Breast Cancer: an Evidence-Based Review of its Safety, Efficacy, and Place in Therapy. Core Evid, 2019, 14:51–70., DOI 10.2147/CE. S217848
van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentje VO, et al. Neoadjuvant Chemotherapy with or without Anthracyclines in the Presence of Dual HER2 Blockade for HER2-Positive Breast Cancer, TRAIN-2): a Multicentre, Open-Label, Randomised, Phase 3 Trial. Lancet Oncol, 2018, 19:1630–40., DOI 10.1016/S1470-2045(18, 30570-9
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Chang Y-K, Co M, and Kwong A. Conversion Rate from Mastectomy to Breast Conservation after Neoadjuvant Dual Target Therapy for HER2-Positive Breast Cancer in the Asian Population. Breast Cancer, 2020, 27:456–63., DOI 10. 1007/s12282-019-01037-3
Munoz-Montano W, Cabrera-Galeana P, Alvarado-Miranda A, Villarreal- Garza C, Mohar A, Olvera A, et al. Prognostic Value of the Pretreatment Neutrophil-To-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer during Neoadjuvant Systemic Treatment. Clin Breast Cancer, 2020, 20:307–16., DOI 10.1016/j.clbc.2019.12.011
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609785
EP 1609793
DI 10.3389/pore.2021.1609785
PG 9
ER
PT J
AU Park, HM
Choi, EJ
Kim, JR
Bae, KY
AF Park, Hui Min
Choi, Eun Jung
Kim, Jae-Ryong
Bae, Kyung Young
TI Immunohistochemical Expressions of Senescence-Associated Secretory Phenotype and Its Association With Immune Microenvironments and Clinicopathological Factors in Invasive Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; breast cancer; senescence; prognosis; markers
ID immunohistochemistry; breast cancer; senescence; prognosis; markers
AB This study was undertaken to investigate immunohistochemical expression of the senescence-associated secretory phenotype (SASP) in invasive breast cancer (IBC) tissues and to determine relationships between SASP positivity and tumor microenvironments and the clinicopathological characteristics of IBC. Immunohistochemistry for senescence markers, that is, high mobility group box-1 (HMGB1), p16, p15, and decoy receptor 2 (DCR2), was performed in tissue microarrays of 1140 IBC samples. Cases positive for at least one of these four markers were considered SASP-positive. Relations between SASP and tumor characteristics, including immune microenvironments (stromal tumor-infiltrating lymphocytes [sTILs] density and numbers of intraepithelial CD103-positive [iCD103 + ] lymphocytes) and clinical outcomes were retrospectively evaluated. HMGB1, p16, p15, or DCR2 was positive in 6.7%, 26.6%, 21.1%, and 26.5%, respectively, of the 1,140 cases. Six hundred and five (53.1%) cases were SASP positive, and SASP positivity was significantly associated with histologic grade 3, high-sTIL and iCD103 + lymphocyte counts, absence of ER or PR, and a high Ki-67 index. Although SASP did not predict breast cancer-specific survival (BCSS) or disease-free survival (DFS) in the entire cohort, SASP positivity in luminal A IBC was associated with poor BCSS and DFS. However, patients with SASP-positive TNBC showed better survival than those with SASP-negative TNBC. In multivariate analysis, SASP positivity was an independent prognostic factor in both luminal A IBC and TNBC, although the effect on prognosis was the opposite. In conclusion, SASP would be involved in the modulation of immune microenvironments and tumor progression in IBC, and its prognostic significance depends on molecular subtype.
C1 [Park, Hui Min] Yeungnam University, College of Medicine, Department of PathologyDaegu, South Korea.
[Choi, Eun Jung] Yeungnam University College of Medicine, Department of SurgeryDaegu, South Korea.
[Kim, Jae-Ryong] Yeungnam University College of Medicine, Department of Biochemistry and Molecular BiologyDaegu, South Korea.
[Bae, Kyung Young] Yeungnam University, College of Medicine, Department of PathologyDaegu, South Korea.
RP Bae, KY (reprint author), Yeungnam University, College of Medicine, Department of Pathology, Daegu, South Korea.
EM ykbae@ynu.ac.kr
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Basisty N, Kale A, Jeon OH, Kuehnemann C, Payne T, and Rao CA. Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development. Plos Biol, 2020, 18(1):e3000599., DOI 10.1371/journal.pbio.3000599
Coppe J-P, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, et al. Senescence-associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the P53 Tumor Suppressor. Plos Biol, 2008, 6(12):e301–2868., DOI 10.1371/journal.pbio.0060301
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609795
EP 1609804
DI 10.3389/pore.2021.1609795
PG 10
ER
PT J
AU Soldos, P
Besenyi, Zs
Hideghety, K
Pavics, L
Heged}us,
Racz, L
Kopper, B
AF Soldos, Peter
Besenyi, Zsuzsanna
Hideghety, Katalin
Pavics, Laszlo
Heged}us, Adam
Racz, Levente
Kopper, Bence
TI Comparison of Shear Wave Elastography and Dynamometer Test in Muscle Tissue Characterization for Potential Medical and Sport Application
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE dynamometry; muscle thickness; muscle stiffness; shear wave elastography; strength parameters
ID dynamometry; muscle thickness; muscle stiffness; shear wave elastography; strength parameters
AB Skeletal muscle status and its dynamic follow up are of particular importance in the management of several diseases where weight and muscle mass loss and, consequently, immobilization occurs, as in cancer and its treatment, as well as in neurodegenerative disorders. But immobilization is not the direct result of body and muscle mass loss, but rather the loss of the maximal tension capabilities of the skeletal muscle. Therefore, the development of a non-invasive and real-time method which can measure muscle tension capabilities in immobile patients is highly anticipated. Our aim was to introduce and evaluate a special ultrasound measurement technique to estimate a maximal muscle tension characteristic which can be used in medicine and also in sports diagnostics. Therefore, we determined the relationship between the results of shear wave elastography measurements and the dynamometric data of individuals. The measurements were concluded on the m. vastus lateralis. Twelve healthy elite athletes took part in our preliminary proof of principle study—five endurance (S) and seven strength (F) athletes showing unambiguously different muscle composition features, nine healthy subjects (H) without prior sports background, and four cancer patients in treatment for a stage 3 brain tumor (T). Results showed a high correlation between the maximal dynamometric isometric torque (Mmax) and mean elasticity value (E) for the non-athletes [(H + T), (r = 0.795)] and for the athletes [(S + F), (r = 0.79)]. For the athletes (S + F), the rate of tension development at contraction (RTDk) and E correlation was also determined (r = 0.84, p < 0.05). Our measurements showed significantly greater E values for the strength athletes with fast muscle fiber dominance than endurance athletes with slow muscle fiber dominance (p < 0.05). Our findings suggest that shear wave ultrasound elastography is a promising method for estimating maximal muscle tension and, also, the human skeletal muscle fiber ratio. These results warrant further investigations with a larger number of individuals, both in medicine and in sports science.
C1 [Soldos, Peter] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Besenyi, Zsuzsanna] University of Szeged, Department of Nuclear MedicineSzeged, Hungary.
[Hideghety, Katalin] University of Szeged, Department of OncotherapySzeged, Hungary.
[Pavics, Laszlo] University of Szeged, Department of Nuclear MedicineSzeged, Hungary.
[Heged}us, Adam] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Racz, Levente] University of Physical Education, Department of KinesiologyBudapest, Hungary.
[Kopper, Bence] University of Physical Education, Department of KinesiologyBudapest, Hungary.
RP Soldos, P (reprint author), University of Physical Education, Department of Kinesiology, Budapest, Hungary.
EM peter.soldos@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609798
EP 1609808
DI 10.3389/pore.2021.1609798
PG 11
ER
PT J
AU Sebestyen, A
Kopper, L
Danko, T
Timar, J
AF Sebestyen, Anna
Kopper, Laszlo
Danko, Titanilla
Timar, Jozsef
TI Hypoxia Signaling in Cancer: From Basics to Clinical Practice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE cancer; hypoxia; angiogenesis; metabolism; therapy
ID cancer; hypoxia; angiogenesis; metabolism; therapy
AB Cancer hypoxia, recognized as one of the most important hallmarks of cancer, affects gene expression, metabolism and ultimately tumor biology-related processes. Major causes of cancer hypoxia are deficient or inappropriate vascularization and systemic hypoxia of the patient (frequently induced by anemia), leading to a unique form of genetic reprogramming by hypoxia induced transcription factors (HIF). However, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling independently of oxygen supply. The consequences of HIF activation in tumors are the angiogenic phenotype, a novel metabolic profile and the immunosuppressive microenvironment. Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance. Accordingly, it seems inevitable to combine various therapeutic modalities of cancer patients by existing anti-hypoxic agents such as anti-angiogenics, anti-anemia therapies or specific signaling pathway inhibitors. It is evident that there is an unmet need in cancer patients to develop targeted therapies of hypoxia to improve efficacies of various anti-cancer therapeutic modalities. The case has been opened recently due to the approval of the first-in-class HIF2α inhibitor.
C1 [Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM jtimar@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609802
EP 1609816
DI 10.3389/pore.2021.1609802
PG 15
ER
PT J
AU Islam, Sh
Kitagawa, T
Kuramitsu, Y
AF Islam, Shajedul
Kitagawa, Takao
Kuramitsu, Yasuhiro
TI Prognostic Significance of Cofilin Isoforms in Patients With Pancreatic Ductal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE biomarker; pancreatic ductal adenocarcinoma; cofilin; proteomics; kaplan-meier
ID biomarker; pancreatic ductal adenocarcinoma; cofilin; proteomics; kaplan-meier
C1 [Islam, Shajedul] Health Sciences University of Hokkaido, Advanced Research Promotion CenterHokkaido, Japan.
[Kitagawa, Takao] Health Sciences University of Hokkaido, Advanced Research Promotion CenterHokkaido, Japan.
[Kuramitsu, Yasuhiro] Health Sciences University of Hokkaido, Advanced Research Promotion CenterHokkaido, Japan.
RP Kuramitsu, Y (reprint author), Health Sciences University of Hokkaido, Advanced Research Promotion Center, Hokkaido, Japan.
EM climates@hoku-iryo-u.ac.jp
CR Lippolis R, and De Angelis M. Proteomics and Human Diseases. J Proteomics Bioinform, 2016, 09:3., DOI 10.4172/jpb.1000391
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Nagy A, Munkacsy G, and Gyorffy B. Pancancer Survival Analysis of Cancer Hallmark Genes. Sci Rep, 2021, 11:6047., DOI 10.1038/s41598-021-84787-5
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609821
EP 1609822
DI 10.3389/pore.2021.1609821
PG 2
ER
PT J
AU Kim, JEJ
Kocsmar, I
Buzas, MGy
Szirtes, I
Rusz, O
Diczhazi, Cs
Szijarto, A
Hritz, I
Schaff, Zs
Kiss, A
Kocsmar,
Lotz, G
AF Kim, Ju Ea Jewel
Kocsmar, Ildiko
Buzas, Miklos Gyorgy
Szirtes, Ildiko
Rusz, Orsolya
Diczhazi, Csaba
Szijarto, Attila
Hritz, Istvan
Schaff, Zsuzsa
Kiss, Andras
Kocsmar, Eva
Lotz, Gabor
TI Efficacy of Clarithromycin Depends on the Bacterial Density in Clarithromycin-Heteroresistant Helicobacter pylori Infections: An In Situ Detected Susceptibility and Quantitative Morphometry-Based Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE fluorescence in situ hybridization; Helicobacter pylori; clarithromycin; antibiotic resistance; heteroresistance; bacterial density
ID fluorescence in situ hybridization; Helicobacter pylori; clarithromycin; antibiotic resistance; heteroresistance; bacterial density
AB The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Clasusceptible bacteria are simultaneously present with the Cla-resistant ones (Claheteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradicationwithCla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.
C1 [Kim, Ju Ea Jewel] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kocsmar, Ildiko] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Buzas, Miklos Gyorgy] Ferencvaros Health Centre, Department of GastroenterologyBudapest, Hungary.
[Szirtes, Ildiko] Peterfy Hospital - National Institute of Traumatology, Department of PharmacyBudapest, Hungary.
[Rusz, Orsolya] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Diczhazi, Csaba] Peterfy Hospital - National Institute of Traumatology, Department of PathologyBudapest, Hungary.
[Szijarto, Attila] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Hritz, Istvan] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Schaff, Zsuzsa] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kocsmar, Eva] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Lotz, G (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM lotz.gabor@med.semmelweisuniv.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2021
VL 27
IS 2
BP 1609863
EP 1609873
DI 10.3389/pore.2021.1609863
PG 11
ER
PT J
AU Xu, N
Guo, H
Li, X
Zhao, Q
Li, J
AF Xu, Ning
Guo, Hui
Li, Xurui
Zhao, Qian
Li, Jianguo
TI A Five-Genes Based Diagnostic Signature for Sepsis-Induced ARDS
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sepsis; ARDS; GO and KEGG analysis; logistic regression model; SVM model
ID sepsis; ARDS; GO and KEGG analysis; logistic regression model; SVM model
AB Background: Acute respiratory distress syndrome (ARDS) is a frequent and serious complication of sepsis without specific and sensitive diagnostic signatures. Methods: The mRNA profiles, including 60 blood samples with sepsis-induced ARDS and 86 blood samples with sepsis alone, were obtained from the Gene Expression Omnibus (GEO). The differently expressed genes (DEGs) were analyzed by limma package of R language. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out using the clusterProfiler package of R. Eventually, multivariate logistic regression model was established through the glm function of R, and support vector machine (SVM) model was constructed via the e1071 package of R. Results: A total of 242 DEGs in GSE32707 and 102 DEGs in GSE66890 were identified. Notably, five genes exhibited significant differences between the two datasets and were considered to be closely associated with the occurrence of ARDS induced by sepsis. Furthermore, functional enrichment analysis based on the DEGs showed there were 80 overlapped GO terms and one KEGG pathway which were significantly enriched in the two datasets. The logistic regression model and SVM model constructed could efficiently distinguish sepsis patients with or without ARDS. Conclusion: In brief, our study suggested that NKG7, SPTA1, FGL2, RGS2, and IFI27 might be potential diagnostic signatures for sepsis-induced ARDS, which contributed to the future exploration in mechanism of ARDS occurrence and development.
C1 [Xu, Ning] Hebei General Hospital, Department of EmergencyShijiazhuang, China.
[Guo, Hui] Hebei General Hospital, Department of EmergencyShijiazhuang, China.
[Li, Xurui] Hebei General Hospital, Department of General PracticeShijiazhuang, China.
[Zhao, Qian] Hebei General Hospital, Department of EmergencyShijiazhuang, China.
[Li, Jianguo] Hebei General Hospital, Department of EmergencyShijiazhuang, China.
RP Li, J (reprint author), Hebei General Hospital, Department of Emergency, Shijiazhuang, China.
EM lijianguo285@outlook.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 580801
EP 580807
DI 10.3389/pore.2021.580801
PG 7
ER
PT J
AU Juris, A
Taylor-Gehman, A
Spencer, B
Schaefer, E
Pameijer, C
AF Juris, Aubrey
Taylor-Gehman, Amanda
Spencer, Brianna
Schaefer, Eric
Pameijer, Colette
TI The Impact of Sarcopenia in Patients with Peritoneal Surface Disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sarcopenia; muscle mass; cytoreduction; outcomes; intraperitoneal chemotherapy; peritoneal surface disease
ID sarcopenia; muscle mass; cytoreduction; outcomes; intraperitoneal chemotherapy; peritoneal surface disease
AB Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is increasingly performed in patients with advanced cancer in the abdomen. This treatment prolongs survival for some patients but is known to have a substantial rate of complications. Choosing patients for this procedure can be difficult, and no clear guidelines exist. Muscle mass is a general measure of a patient’s wellness, meaning that patients with low muscle mass for their body weight tend to have more complications from treatment and overall do worse. We evaluated muscle mass prior to surgery in our Cytoreductive surgery/ hyperthermic intraperitoneal chemotherapy population to assess how many patients have low muscle mass and the impact on outcomes, such as length of hospital stay, complications and survival. We find that about 25% of our patient population has low muscle mass, and low muscle mass is associated with a higher burden of cancer and shorter survival. We were able to evaluate muscle mass in a small number of patients after surgery, expecting to find decreased muscle mass in all the patients after a complex operation and long recovery. In fact, none of the patients had low muscle mass, including those who were low prior to surgery.
C1 [Juris, Aubrey] The Pennsylvania State University, College of Medicine, Department of SurgeryHershey, PA, USA.
[Taylor-Gehman, Amanda] The Pennsylvania State University, College of Medicine, Department of Family and Community MedicineHershey, PA, USA.
[Spencer, Brianna] The Pennsylvania State University, College of Medicine, Department of SurgeryHershey, PA, USA.
[Schaefer, Eric] The Pennsylvania State University, College of Medicine, Department of Public Health SciencesHershey, PA, USA.
[Pameijer, Colette] The Pennsylvania State University, College of Medicine, Department of SurgeryHershey, PA, USA.
RP Pameijer, C (reprint author), The Pennsylvania State University, College of Medicine, Department of Surgery, Hershey, USA.
EM cpameijer@pennstatehealth.psu.edu
CR Chemama S, Bayar MA, Lanoy E, Ammari S, Stoclin A, Goere D, et al. Sarcopenia is associated with chemotherapy toxicity in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. Ann Surg Oncol, 2016). 23(12):3891–8., DOI 10.1245/s10434-016-5360-7
van Vugt JLA, Braam HJ, van Oudheusden TR, Vestering A, Bollen TL, Wiezer MJ, et al. Skeletal muscle depletion is associated with severe postoperative complications in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol, 2015). 22(11):3625–31., DOI 10.1245/s10434-015- 4429-z
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 638857
EP 638861
DI 10.3389/pore.2021.638857
PG 5
ER
PT J
AU Qi, W
Yan, Q
Lv, M
Song, D
Wang, X
Tian, K
AF Qi, Wei
Yan, Qian
Lv, Ming
Song, Delei
Wang, Xianbin
Tian, Kangsong
TI Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; risk score; osteosarcoma; autophagy-related genes; nomogram
ID prognosis; risk score; osteosarcoma; autophagy-related genes; nomogram
AB Background: Osteosarcoma is a common malignancy of bone with inferior survival outcome. Autophagy can exert multifactorial influence on tumorigenesis and tumor progression. However, the specific function of genes related to autophagy in the prognosis of osteosarcoma patients remains unclear. Herein, we aimed to explore the association of genes related to autophagy with the survival outcome of osteosarcoma patients. Methods: The autophagy-associated genes that were related to the prognosis of osteosarcoma were optimized by LASSO Cox regression analysis. The survival of osteosarcoma patients was forecasted by multivariate Cox regression analysis. The immune infiltration status of 22 immune cell types in osteosarcoma patients with high and low risk scores was compared by using the CIBERSORT tool. Results: The risk score model constructed according to 14 autophagy-related genes (ATG4A, BAK1, BNIP3, CALCOCO2, CCL2, DAPK1, EGFR, FAS, GRID2, ITGA3, MYC, RAB33B, USP10, and WIPI1) could effectively predict the prognosis of patients with osteosarcoma. A nomogram model was established based on risk score and metastasis. Conclusion: Autophagy-related genes were identified as pivotal prognostic signatures, which could guide the clinical decision making in the treatment of osteosarcoma.
C1 [Qi, Wei] Zibo Central Hospital, Department ofWest Hospital Orthopaedic TraumaZibo, China.
[Yan, Qian] Zibo Central Hospital, Department of Information SectionZibo, China.
[Lv, Ming] Zibo Central Hospital, Department ofWest Hospital Orthopaedic TraumaZibo, China.
[Song, Delei] Zibo Central Hospital, Department ofWest Hospital Orthopaedic TraumaZibo, China.
[Wang, Xianbin] Zibo Central Hospital, Department of Eastern Hospital Orthopaedic TraumaZibo, China.
[Tian, Kangsong] Zibo Central Hospital, Department ofWest Hospital Orthopaedic TraumaZibo, China.
RP Tian, K (reprint author), Zibo Central Hospital, Department ofWest Hospital Orthopaedic Trauma, Zibo, China.
EM tiankangsong@outlook.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609782
EP 1609795
DI 10.3389/pore.2021.1609782
PG 14
ER
PT J
AU Xu, M
Yuan, L
Wang, Y
Chen, Sh
Zhang, L
Zhang, X
AF Xu, Mingyue
Yuan, Lijun
Wang, Yan
Chen, Shuo
Zhang, Lin
Zhang, Xipeng
TI Integrative Analysis of DNA Methylation and Gene Expression Profiles Identifies Colorectal Cancer-Related Diagnostic Biomarkers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Colorectal cancer; DNA methylation; logistic regression model; CpG island methylator phenotype; The Cancer Genome Atlas; Gene Expression Omnibus; diagnosis
ID Colorectal cancer; DNA methylation; logistic regression model; CpG island methylator phenotype; The Cancer Genome Atlas; Gene Expression Omnibus; diagnosis
AB Background: Colorectal cancer (CRC) is a common human malignancy worldwide. The prognosis of patients is largely frustrated by delayed diagnosis or misdiagnosis. DNA methylation alterations have been previously proved to be involved in CRC carcinogenesis. Methods: In this study, we proposed to identify CRC-related diagnostic biomarkers by analyzing DNA methylation and gene expression profiles. TCGA-COAD datasets downloaded from the Cancer Genome Atlas (TCGA) were used as the training set to screen differential expression genes (DEGs) and methylation CpG sites (dmCpGs) in CRC samples. A logistic regression model was constructed based on hyper-methylated CpG sites which were located in downregulated genes for CRC diagnosis. Another two independent datasets from the Gene Expression Omnibus (GEO) were used as a testing set to evaluate the performance of the model in CRC diagnosis. Results: We found that CpG island methylator phenotype (CIMP) was a potential signature of poor prognosis by dividing CRC samples into CIMP and noCIMP groups based on a set of CpG sites with methylation standard deviation (sd) > 0.2 among CRC samples and low methylation levels (mean β < 0.05) in adjacent samples. Hypermethylated CpGs tended to be more closed to CpG island (CGI) and transcription start site (TSS) relative to hypo-methylated CpGs (p-value < 0.05, Fisher exact test). A logistic regression model was finally constructed based on two hyper-methylated CpGs, which had an area under receiver operating characteristic curve of 0.98 in the training set, and 0.85 and 0.95 in the two independent testing sets. Conclusions: In conclusion, our study identified promising DNA methylation biomarkers for CRC diagnosis.
C1 [Xu, Mingyue] Tianjin Union Medical Center, Department of Colorectal SurgeryTianjin, China.
[Yuan, Lijun] Tianjin Union Medical Center, Department of Colorectal SurgeryTianjin, China.
[Wang, Yan] Shanghai Pudong New Area People’s Hospital, Department of Traditional Chinese MedicineShanghai, China.
[Chen, Shuo] Tianjin Union Medical Center, Department of Colorectal SurgeryTianjin, China.
[Zhang, Lin] Tianjin Union Medical Center, Department of Colorectal SurgeryTianjin, China.
[Zhang, Xipeng] Tianjin Union Medical Center, Department of Colorectal SurgeryTianjin, China.
RP Zhang, X (reprint author), Tianjin Union Medical Center, Department of Colorectal Surgery, Tianjin, China.
EM zhangxipeng18212@outlook.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609784
EP 1609790
DI 10.3389/pore.2021.1609784
PG 7
ER
PT J
AU Hua, Y
Gao, L
Li, X
AF Hua, Yu
Gao, Lihong
Li, Xiaobo
TI Comprehensive Analysis of Metabolic Genes in Breast Cancer Based on Multi-Omics Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; prognosis; mutation; metabolism; WGCNA
ID breast cancer; prognosis; mutation; metabolism; WGCNA
AB Background: Reprogramming of cell metabolism is one of the most important hallmarks of breast cancer. This study aimed to comprehensively analyze metabolic genes in the initiation, progression, and prognosis of breast cancer. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) in breast cancer were downloaded including RNA-seq, copy number variation, mutation, and DNA methylation. A gene co-expression network was constructed by the weighted correlation network analysis (WGCNA) package in R. Association of metabolic genes with tumor-related immune cells and clinical parameters were also investigated. Results: We summarized 3,620 metabolic genes and observed mutations in 2,964 genes, of which the most frequently mutated were PIK3CA (51%), TNN (26%), and KMT2C (15%). Four genes (AKT1, ERBB2, KMT2C, and USP34) were associated with survival of breast cancer. Significant association was detected in the tumor mutation burden (TMB) of metabolic genes with T stage (p = 0.045) and N stage (p = 0.004). Copy number variations were significantly associated with recurrence and prognosis of breast cancer. The coexpression network for differentially expressed metabolic genes by WGCNA suggested that the modules were associated with glycerophospholipid, arachidonic acid, carbon, glycolysis/gluconeogenesis, and pyrimidine/purine metabolism. Glycerophospholipid metabolism correlated with most of the immune cells, while arachidonic acid metabolism demonstrated a significant correlation with endothelial cells. Methylation and miRNA jointly regulated 14 metabolic genes while mutation and methylation jointly regulated PIK3R1. Conclusion: Based on multi-omics data of somatic mutation, copy number variation, mRNA expression, miRNA expression, and DNA methylation, we identified a series of differentially expressed metabolic genes. Metabolic genes are associated with tumorrelated immune cells and clinical parameters, which might be therapy targets in future clinical application.
C1 [Hua, Yu] The First Affiliated Hospital of China Medical University, Department of NursingShenyang, China.
[Gao, Lihong] The First Affiliated Hospital of China Medical University, Department of NursingShenyang, China.
[Li, Xiaobo] The First Affiliated Hospital of China Medical University, Department of NursingShenyang, China.
RP Li, X (reprint author), The First Affiliated Hospital of China Medical University, Department of Nursing, Shenyang, China.
EM lnshy110001@163.com
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Rahman MM, Brane AC, and Tollefsbol TO. MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer. Cells, 2019, 8(10): 1214., DOI 10.3390/ cells8101214
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609789
EP 1609798
DI 10.3389/pore.2021.1609789
PG 10
ER
PT J
AU Zhu, L
Ling, Ch
Xu, T
Zhang, J
Zhang, Y
Liu, Y
Fang, Ch
Yang, L
Zhuang, W
Wang, R
Ping, J
Wang, M
AF Zhu, Lili
Ling, Chunrun
Xu, Tao
Zhang, Jinglin
Zhang, Yujie
Liu, Yingjie
Fang, Chao
Yang, Lie
Zhuang, Wen
Wang, Rui
Ping, Jie
Wang, Mojin
TI Clinicopathological Features and Survival of Signet-Ring Cell Carcinoma and Mucinous Adenocarcinoma of Right Colon, Left Colon, and Rectum
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; colorectal carcinoma; signet-ring cell carcinoma; histological subtype; SEER
ID survival; colorectal carcinoma; signet-ring cell carcinoma; histological subtype; SEER
AB Histological subtype plays an important role in the different clinical characteristics and survival outcomes of patients with colorectal carcinoma (CRC). However, in previous studies, the influences of tumor locations and tumor stages have not been strictly controlled. This study focused on the assessment of the prognostic value of each histological subtype in different tumor locations and tumor stages of CRC. We used the Surveillance, Epidemiology, and End Results (SEER) database (1973–2011) to analyze 818,229 CRC patients with different clinical and pathological features, and analyzed the prognostic value of each histological subtype. Under the condition of stratification by tumor stage, signet-ring cell carcinoma (SRCC) presented the worst survival in each stage of right colon cancer (stage I, log-rank, p = 0.002, stages II, III, and IV, log-rank, p < 0.001), rectal cancer (RC) (log-rank, p < 0.001), and in stages II, III, and IV of left colon cancer (log-rank, p < 0.001). Multivariate survival analysis suggested SRCC subtype, male gender, age ≥ 70 years, tumor size ≥ 5 cm, stage progression, and poor differentiation were all significant factors worsening survival in CRC (p < 0.001, respectively). Mucinous adenocarcinoma (MC) histological subtype proved to be an independent protective factor for the prognosis of right colon cancer (p = 0.003). Overall, in our study, the results suggested SRCC had the worst survival among the three histological subtypes of CRC. MC was associated with favorable prognosis in right colon cancer but not with other tumor locations.
C1 [Zhu, Lili] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Ling, Chunrun] The People’s Hospital of Guangxi Zhuang Autonomous Region, Department of General and Pediatric SurgeryNanning, China.
[Xu, Tao] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Zhang, Jinglin] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Zhang, Yujie] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Liu, Yingjie] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Fang, Chao] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Yang, Lie] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Zhuang, Wen] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
[Wang, Rui] Sichuan University, West China Hospital, Department of GastroenterologyChengdu, China.
[Ping, Jie] Vanderbilt University Medical Center, Division of EpidemiologyNashville, TN, USA.
[Wang, Mojin] Sichuan University, West China Hospital, Department of Gastrointestinal SurgeryChengdu, China.
RP Wang, M (reprint author), Sichuan University, West China Hospital, Department of Gastrointestinal Surgery, Chengdu, China.
EM wangmojin2001@163.com
CR Song IH, Hong S-M, Yu E, Yoon YS, Park IJ, Lim S-B, et al. Signet Ring Cell Component Predicts Aggressive Behaviour in Colorectal Mucinous Adenocarcinoma. Pathology, 2019, 51(4):384–91., DOI 10.1016/ j.pathol.2019.03.001
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Green JB, Timmcke AE, Mitchell WT, Hicks TC, Gathright BJ, Jr, and Ray JE. Mucinous Carcinoma-Just Another colon Cancer? Dis colon rectum, 1993, 36(1):49–54., DOI 10.1007/bf02050301
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Bittorf B, Merkel S, Matzel K, Wein A, Dimmler A, and Hohenberger W. Primary Signet-Ring Cell Carcinoma of the Colorectum. Langenbecks Arch Surg, 2004, 389(3):178–83., DOI 10.1007/s00423-004-0474-y
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Hugen N, Verhoeven RH, Lemmens VE, van Aart CJ, Elferink MA, Radema SA, et al. Colorectal Signet-Ring Cell Carcinoma: Benefit from Adjuvant Chemotherapy but a Poor Prognostic Factor. Int J Cancer, 2015, 136(2): 333–9., DOI 10.1002/ijc.28981
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Razenberg LGEM, van Gestel YRBM, Lemmens VEPP, de Wilt JHW, Creemers G-J, and de Hingh IHJT. The Prognostic Relevance of Histological Subtype in Patients with Peritoneal Metastases from Colorectal Cancer: A Nationwide Population-Based Study. Clin Colorectal Cancer, 2015, 14(4):e13–e19., DOI 10.1016/j.clcc.2015.05.011
Shen H, Yang J, Huang Q, Jiang MJ, Tan YN, Fu JF, et al. Different Treatment Strategies and Molecular Features between Right-Sided and Left-Sided colon Cancers. Wjg, 2015, 21(21):6470–8., DOI 10.3748/ wjg.v21.i21.6470
Gao XH, Yu GY, Gong HF, Liu LJ, Xu Y, Hao LQ, et al. Differences of Protein Expression Profiles, KRAS and BRAF Mutation, and Prognosis in Right-Sided colon, Left-Sided colon and Rectal Cancer. Sci Rep, 2017, 7(1):7882., DOI 10.1038/s41598-017-08413-z
He W-Z, Liao F-X, Jiang C, Kong P-F, Yin C-X, Yang Q, et al. Primary Tumor Location as a Predictive Factor for First-Line Bevacizumab Effectiveness in Metastatic Colorectal Cancer Patients. J Cancer, 2017, 8(3):388–94., DOI 10.7150/jca.16804
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Dajani YF, Zayid I, Malatjalian DA, and Kamal MF. Colorectal Cancer in Jordan and Nova Scotia: a Comparative Epidemiologic and Histopathologic Study. Cancer, 1980, 46(2):420–8., DOI 10.1002/1097-0142(19800715)46:2
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Bertagnolli MM, Niedzwiecki D, Compton CC, Hahn HP, Hall M, Damas B, et al. Microsatellite Instability Predicts Improved Response to Adjuvant Therapy with Irinotecan, Fluorouracil, and Leucovorin in Stage III colon Cancer: Cancer and Leukemia Group B Protocol 89803. Jco, 2009, 27(11): 1814–21., DOI 10.1200/jco.2008.18.2071
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Lee C-T, Huang Y-C, Hung L-Y, Chow N-H, Su P-F, Ho C-L, et al. Serrated Adenocarcinoma Morphology in Colorectal Mucinous Adenocarcinoma is Associated with Improved Patient Survival. Oncotarget, 2017, 8(21):35165–75., DOI 10.18632/oncotarget.16815
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609800
EP 1609808
DI 10.3389/pore.2021.1609800
PG 9
ER
PT J
AU Kelany, M
Barth, Th
Salem, D
Shakweer, M
AF Kelany, Mohamed
Barth, FE. Thomas
Salem, Dina
Shakweer, M. Marwa
TI Prevalence and Prognostic Implications of PD-L1 Expression in Soft Tissue Sarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; PD-L1 expression; soft tissue sarcomas; prevalence
ID biomarker; prognosis; PD-L1 expression; soft tissue sarcomas; prevalence
AB Background: PD-L1 expression differs from 19 to 92% in various cancer subtypes. Its expression carries a worse prognostic value in various malignancies and could also be used as a predictive marker for immune checkpoint inhibitor response. This study aimed to explore the prevalence of PD-L1 expression in soft tissue sarcomas and the correlation of PD-L1 expression with clinicopathological features. Patients and Methods: The tissue samples of 50 patients with STS were tested for PDL1 expression using immunohistochemistry (IHC). We followed a 6-step proportional scoring system. The patients were treated at Ain Shams University Hospital from 2011 to 2017. We also explored the correlation of PD-L1 expression with different clinical features of the patients. The chi-square test was used to calculate the differences among variables. Results: Twelve cases (24%) showed positive PD-L1 expression with the highest prevalence in rhabdomyosarcoma and desmoid tumors (2/2 and 2/3 cases, respectively), followed by GIST in 2/4 cases and liposarcoma in 3/11 cases. Patients with positive PD-L1 expression showed a trend for worse survival, with a median overall survival of 11 months vs. 19 months for patients with negative PD-L1 expression (p-value = 0.1) and a mean PFS of 6 months vs. 11 months for patients with negative PD-L1 expression (p-value = 0.1). However, these findings did not reach statistical significance. Conclusion: Although the results did not reach statistical significance due to the small number of cases, PD-L1 expression could represent a prognostic factor for poor outcome. Larger clinical trials are recommended for the validation of PD-L1 as a poor prognostic biomarker.
C1 [Kelany, Mohamed] Ain Shams University, Department of Clinical OncologyCairo, Egypt.
[Barth, FE. Thomas] Ulm University, Department of PathologyUlm, Germany.
[Salem, Dina] Ain Shams University, Department of Clinical OncologyCairo, Egypt.
[Shakweer, M. Marwa] Ain Shams Faculty of Medicine, Department of PathologyCairo, Egypt.
RP Kelany, M (reprint author), Ain Shams University, Department of Clinical Oncology, Cairo, Egypt.
CR Burningham Z, Hashibe M, Spector L, and Schiffman JD. The Epidemiology of Sarcoma. Clin Sarcoma Res, 2012, 2(1):14., DOI 10.1186/2045-3329-2-14
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Chen DS, and Mellman I. Oncology Meets Immunology: The Cancer- Immunity Cycle. Immunity, 2013, 39(1):1–10., DOI 10.1016/ j.immuni.2013.07.012
Martin V, Raica M, and Cimpean AM. First-Line Immunophenotyping in the Pathologic Diagnosis of Soft Tissue Tumors. 2004;54(2):122–7.
Kim C, Kim EK, Jung H, Chon HJ, Han JW, Shin K-H, et al. Prognostic Implications of PD-L1 Expression in Patients with Soft Tissue Sarcoma. BMC Cancer, 2016, 16(1):434., DOI 10.1186/s12885-016-2451-6
Kim C, Kim EK, Han JW, Chon HJ, Heo SJ, Lee YH, et al. Clinical Pattern and Implication of PD-L1 Expression in Soft-Tissue Sarcoma. Jco, 2015, 33:10565., DOI 10.1200/jco.2015.33.15_suppl.10565
D’Angelo SP, Shoushtari AN, Agaram NP, Kuk LX, Qin L-X, Dickson MA, et al. Prevalence of Tumor-Infiltrating Lymphocytes and PD-L1 Expression in the Soft Tissue SarcomaMicroenvironment. Hum Pathol, 2015, 46(3):357–65., DOI 10.1016/j.humpath.2014.11.001
Jo VY, and Fletcher CDM. WHO Classification of Soft Tissue Tumours: an Update Based on the 2013, 4th, Edition. Pathology, 2014, 46(2):95–104., DOI 10.1097/PAT.0000000000000050
Herbst RS, Baas P, Kim D-W, Felip E, Perez-Gracia JL, Han J-Y, et al. Pembrolizumab versus Docetaxel for Previously Treated, PD-L1-Positive, Advanced Non-small-cell Lung Cancer, KEYNOTE-010): a Randomised Controlled Trial. Lancet, 2016, 387:1540–50., DOI 10.1016/S0140-6736(15, 01281-7
Scheel AH, Dietel M, Heukamp LC, Johrens K, Kirchner T, Reu S, et al. Harmonized PD-L1 Immunohistochemistry for Pulmonary Squamous-Cell and Adenocarcinomas. Mod Pathol, 2016, 29(10):1165–72., DOI 10.1038/ modpathol.2016.117
Boxberg M, Steiger K, Lenze U, Rechl H, von Eisenhart-Rothe R, Wortler K, et al. PD-L1 and PD-1 and Characterization of Tumor-Infiltrating Lymphocytes in High Grade Sarcomas of Soft Tissue – Prognostic Implications and Rationale for Immunotherapy. OncoImmunology, 2018, 7(3)., DOI 10.1080/2162402x.2017.1389366
Kim J, Moon YJ, Kwon KS, Bae JS, Wagle S, Kim KM, et al. Tumor Infiltrating PD1-Positive Lymphocytes and the Expression of PD-L1 Predict Poor Prognosis of Soft Tissue Sarcomas. PLoS ONE, 2013, 8(12):1–9., DOI 10.1371/journal.pone.0082870
Chowdhury F, Dunn S, Mitchell S, Mellows T, Ashton-Key M, and Gray JC. PD-L1 and CD8 + PD1 + Lymphocytes Exist as Targets in the Pediatric Tumor Microenvironment for Immunomodulatory Therapy. OncoImmunology, 2015, 4(10)., DOI 10.1080/2162402x.2015.1029701
Que Y, Xiao W, Guan Y, Liang Y, Yan S, Chen H, et al. PD-L1 Expression Is Associated with FOXP3 + Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis. J Cancer 2018;8:2018–25., DOI 10.7150/jca.18683
Patel KR, Martinez A, Stahl JM, Logan SJ, Perricone AJ, Ferris MJ, et al. Increase in PD-L1 Expression after Pre-operative Radiotherapy for Soft Tissue Sarcoma. OncoImmunology, 2018, 7(7)., DOI 10.1080/ 2162402x.2018.1442168
Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, et al. T-cell Infiltration and Clonality Correlate with Programmed Cell Death Protein 1 and Programmed Death-Ligand 1 Expression in Patients with Soft Tissue Sarcomas. Cancer, 2017, 123(17)., DOI 10.1002/cncr.30726
van Erp AEM, Versleijen-Jonkers YMH, Hillebrandt-Roeffen MHS, van Houdt L, Gorris MAJ, van Dam LS, et al. Expression and Clinical Association of Programmed Cell Death-1, Programmed Death-Ligand-1 and CD8+ Lymphocytes in Primary Sarcomas Is Subtype Dependent. Oncotarget, 2017, 8(41)., DOI 10.18632/oncotarget.19071
Paydas S, Bagir EK, Deveci MA, and Gonlusen G. Clinical and Prognostic Significance of PD-1 and PD-L1 Expression in Sarcomas. Med Oncol, 2016, 33(8)., DOI 10.1007/s12032-016-0807-z
Bertucci F, Finetti P, Perrot D, Leroux A, Collin F, le Cesne A, et al. PDL1 Expression Is a Poor-Prognosis Factor in Soft-Tissue Sarcomas. OncoImmunology, 2017, 6(3)., DOI 10.1080/2162402x.2016.1278100
Budczies J, Mechtersheimer G, Denkert C, Klauschen F, Mughal SS, Chudasama P, et al. PD-L1, CD274, Copy Number Gain, Expression, and Immune Cell Infiltration as Candidate Predictors for Response to Immune Checkpoint Inhibitors in Soft-Tissue Sarcoma. OncoImmunology, 2017, 6(3)., DOI 10.1080/2162402x.2017.1279777
Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, et al. PD-1 Is Expressed by Tumor-Infiltrating Immune Cells and Is Associated with Poor Outcome for Patients with Renal Cell Carcinoma. Clin Cancer Res, 2007, 13:1757–61., DOI 10.1158/1078-0432.CCR-06-2599
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609804
EP 1609809
DI 10.3389/pore.2021.1609804
PG 6
ER
PT J
AU Tian, X
Xu, WH
Wu, JL
Gan, HL
Wang, HK
Gu, WJ
Qu, YY
Zhang, HL
Ye, DW
AF Tian, Xi
Xu, Wen-Hao
Wu, Jun-Long
Gan, Hua-Lei
Wang, Hong-Kai
Gu, Wei-Jie
Qu, Yuan-Yuan
Zhang, Hai-Liang
Ye, Ding-Wei
TI Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE somatic mutation; clear cell papillary renal cell carcinoma; germline mutation; fanconi anemia pathway; second primary malignancy
ID somatic mutation; clear cell papillary renal cell carcinoma; germline mutation; fanconi anemia pathway; second primary malignancy
AB Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.
C1 [Tian, Xi] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Xu, Wen-Hao] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Wu, Jun-Long] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Gan, Hua-Lei] Fudan University, Shanghai Medical College, Department of OncologyShanghai, China.
[Wang, Hong-Kai] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Gu, Wei-Jie] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Qu, Yuan-Yuan] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Zhang, Hai-Liang] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
[Ye, Ding-Wei] Fudan University, Shanghai Cancer Center, Department of UrologyShanghai, China.
RP Ye, DW (reprint author), Fudan University, Shanghai Cancer Center, Department of Urology, Shanghai, China.
EM dwyelie@163.com
CR Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clin, 2021, 71(3):209–49., DOI 10.3322/caac.21660
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Gobbo S, Eble JN, Grignon DJ, Martignoni G, MacLennan GT, Shah RB, et al. Clear Cell Papillary Renal Cell Carcinoma. Am J Surg Pathol, 2008, 32(8): 1239–45., DOI 10.1097/pas.0b013e318164bcbb
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609809
EP 1609816
DI 10.3389/pore.2021.1609809
PG 8
ER
PT J
AU Dong, Y
Tian, J
Yan, B
Lv, K
Li, J
Fu, D
AF Dong, Yinlei
Tian, Junjie
Yan, Bingqian
Lv, Kun
Li, Ji
Fu, Deliang
TI Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE overall survival; pancreatic cancer; nomogram; liver metastasis; prognostic signature; R0 resection
ID overall survival; pancreatic cancer; nomogram; liver metastasis; prognostic signature; R0 resection
AB It is widely acknowledged that metastasis determines the prognosis of pancreatic adenocarcinoma (PAAD), and the liver is the most primary distant metastatic location of PAAD. It is worth exploring the value of liver-metastasis-related genetic prognostic signature (LM-PS) in predicting the clinical outcomes of PAAD patients post R0 resection. We collected 65 tumors and 165 normal pancreatic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx), respectively. Differentially expressed genes (DEGs) between primary tumor and normal pancreatic samples were intersected with DEGs between primary tumor samples with liver metastasis and those without new tumor events. The intersected 45 genes were input into univariate Cox regression analysis to identify the prognostic genes. Thirty-three prognostic livermetastasis- related genes were identified and included in least absolute shrinkage and selection operator (LASSO) analysis to develop a seven-gene LM-PS, which included six risk genes (ANO1, FAM83A, GPR87, ITGB6, KLK10, and SERPINE1) and one protective gene (SMIM32). The PAAD patients were grouped into low- and high-risk groups based on the median value of risk scores. The LM-PS harbored an independent predictive ability to distinguish patients with a high-risk of death and liver metastasis after R0 resection. Moreover, a robust prognostic nomogram based on LM-PS, the number of positive lymph nodes, and histologic grade were established to predict the overall survival of PAAD patients. Besides, a transcription factor-microRNA coregulatory network was constructed for the seven LM-PS genes, and the immune infiltration and genomic alterations were systematically explored in the TGCA-PAAD cohort.
C1 [Dong, Yinlei] Fudan University, Huashan Hospital, Department of Pancreatic Surgery, Pancreatic Disease InstituteShanghai, China.
[Tian, Junjie] Zhejiang University, School of Medicine, The First Affiliated Hospital, Department of UrologyHangzhou, China.
[Yan, Bingqian] National Children’s Medical Center, Children’s Hospital of Fudan UniversityShanghai, China.
[Lv, Kun] Fudan University, Huashan Hospital, Department of RadiologyShanghai, China.
[Li, Ji] Fudan University, Huashan Hospital, Department of Pancreatic Surgery, Pancreatic Disease InstituteShanghai, China.
[Fu, Deliang] Fudan University, Huashan Hospital, Department of Pancreatic Surgery, Pancreatic Disease InstituteShanghai, China.
RP Fu, D (reprint author), Fudan University, Huashan Hospital, Department of Pancreatic Surgery, Pancreatic Disease Institute, Shanghai, China.
EM surgeonfu@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609822
EP 1609838
DI 10.3389/pore.2021.1609822
PG 17
ER
PT J
AU Wang, X
Yang, Q
Liu, N
Bian, Q
Gao, M
Hou, X
AF Wang, Xinzhuang
Yang, Quan
Liu, Nan
Bian, Qilong
Gao, Ming
Hou, Xu
TI Clinical Value of TXNDC12 Combined With IDH and 1p19q as Biomarkers for Prognosis of Glioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glioma; prognosis; TXNDC12; IDH; 1p19q
ID glioma; prognosis; TXNDC12; IDH; 1p19q
AB Background: Glioma is the primary malignant tumor of the central nervous system and presents high mortality and disability rates under existing treatment measures. Thioredoxin domain-containing 12 (TXNDC12) has been shown to play an important role in various malignant tumors. Therefore, we explored the clinicopathological characteristics of TXNDC12 in glioma to bring to light new ideas in its treatment. Methods: We obtained data packages related to TXNDC12 expression status in gliomas from public databases. We analyzed glioma TXNDC12 expression and patient survival status and validated the above results using glioma specimens from our institution. Next, we analyzed the value of TXNDC12 in combination with 1p19q and isocitrate dehydrogenase (IDH) on the prognosis of glioma by regression model and receiver operating characteristic curve (ROC). Finally, we explored the function of related genes by GO analysis and KEGG analysis. Results: Compared with normal brain tissue, the expression of TXNDC12 in glioma cells, regarding bothmRNA and protein levels, was significantly upregulated. The survival time of patients with high-expression of TXNDC12 in glioma cells was shortened. In the World Health Organization pathological classification, IDH status, 1p19q status, and IDH combined with 1p19q subgroups, the expression of TXNDC12 increased with the deterioration of the above indicators. Tumor local immune analysis showed that the immune cell infiltration in TXNDC12 high-expressing glioma tissue increased, the tumor purity was reduced. GO and KEGG analyses indicated that TXNDC12 may be involved in the malignant prognosis of glioma through glycosylation and antigen processing and presentation. Conclusion: We showed that TXNDC12 is significantly highly expressed in gliomas. This high expression predicts the poor prognosis of glioma patients and is related to the gliomas’ local immune microenvironment. As a tumor-related gene, TXNDC12 may be used as a new prognostic judgment molecule.
C1 [Wang, Xinzhuang] Zhengzhou University, First Affiliated Hospital, Department of NeurosurgeryZhengzhou, China.
[Yang, Quan] The First Affiliated Hospital of Harbin Medical University, Department of NeurosurgeryHarbin, China.
[Liu, Nan] The First Affiliated Hospital of Harbin Medical University, Department of NeurosurgeryHarbin, China.
[Bian, Qilong] Heze Municipal Hospital, Department of NeurosurgeryHeze, China.
[Gao, Ming] The First Affiliated Hospital of Harbin Medical University, Department of NeurosurgeryHarbin, China.
[Hou, Xu] The First Affiliated Hospital of Harbin Medical University, Department of NeurosurgeryHarbin, China.
RP Hou, X (reprint author), The First Affiliated Hospital of Harbin Medical University, Department of Neurosurgery, Harbin, China.
EM houxu1983@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609825
EP 1609838
DI 10.3389/pore.2021.1609825
PG 14
ER
PT J
AU Umar, IM
Hassan, W
Murtaza, G
Buabeid, M
Arafa, E
Irfan, MH
Asmawi, ZM
Huang, X
AF Umar, Ihtisham Muhammad
Hassan, Waseem
Murtaza, Ghulam
Buabeid, Manal
Arafa, Elshaimaa
Irfan, Muhammad Hafiz
Asmawi, Zaini Mohd
Huang, Xianju
TI The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE cell cycle; adipokines; mesenchymal transition; leptin signaling; obesity derived cancers
ID cell cycle; adipokines; mesenchymal transition; leptin signaling; obesity derived cancers
AB A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.
C1 [Umar, Ihtisham Muhammad] COMSATS University Islamabad, Lahore Campus, Department of PharmacyLahore, Pakistan.
[Hassan, Waseem] COMSATS University Islamabad, Lahore Campus, Department of PharmacyLahore, Pakistan.
[Murtaza, Ghulam] COMSATS University Islamabad, Lahore Campus, Department of PharmacyLahore, Pakistan.
[Buabeid, Manal] Ajman University, Department of Clinical SciencesAjman, United Arab Emirates.
[Arafa, Elshaimaa] Ajman University, Department of Clinical SciencesAjman, United Arab Emirates.
[Irfan, Muhammad Hafiz] University of Sargodha, Department of PharmacySargodha, Pakistan.
[Asmawi, Zaini Mohd] University of Science Malaysia, School of Pharmaceutical SciencesPulau Pinang, Malaysia.
[Huang, Xianju] South-Central University for Nationalities, College of PharmacyWuhan, China.
RP Murtaza, G (reprint author), COMSATS University Islamabad, Lahore Campus, Department of Pharmacy, Lahore, Pakistan.
EM gmdogar356@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609828
EP 1609851
DI 10.3389/pore.2021.1609828
PG 24
ER
PT J
AU Xie, J
Kong, X
Wang, W
Li, Y
Lin, M
Li, H
Chen, J
Zhou, W
He, J
Wu, H
AF Xie, Jing
Kong, Xue
Wang, Wei
Li, Yuan
Lin, Mengyu
Li, Heng
Chen, Jingjing
Zhou, Wenchao
He, Jie
Wu, Haibo
TI Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PFS; oligodendroglioma; vasculogenic mimicry; ATM; ATR
ID PFS; oligodendroglioma; vasculogenic mimicry; ATM; ATR
AB Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. In this study, VM-positive cases were detected in 28 (20.6%) out of 136 oligodendroglioma samples, significantly associated with higher WHO grade, lower Karnofsky performance status (KPS) scores, and recurrent tumor (p < 0.001, p = 0.040, and p = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor (p < 0.001), whereas no significant difference was detected in overall survival (OS) between these patients. High levels of phosphorylate serine/threonine kinases Ataxia-telangiectasia mutated (pATM) and phosphorylate Ataxia-telangiectasia and Rad3-Related (pATR) were detected in 31 (22.8%) and 34 (25.0%), respectively out of 136 oligodendroglioma samples. Higher expressions of pATM and pATR were both associated with a shorter PFS (p < 0.001 and p < 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (rs = 0.435, p < 0.001 and rs = 0.317, p < 0.001). Besides, Hypoxia-inducible factor-1α (HIF1α) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe (p = 0.010 and p = 0.029). However, no obvious connection was detected between HIF1α expression and VM formation (p = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients (p < 0.001, HR = 7.928, 95%CI: 3.382–18.584, and p = 0.007, HR = 4.534, 95%CI: 1.504–13.675, respectively). VM is a potential prognosticator for tumor progression in oligodendroglioma patients. Phosphorylation of ATM and ATR linked to treatment-resistance may be associated with VM formation. The role of VM in tumor progression and the implication of pATM/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment.
C1 [Xie, Jing] Shandong University, School of MedicineJinan, China.
[Kong, Xue] University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of PathologyHefei, China.
[Wang, Wei] University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of PathologyHefei, China.
[Li, Yuan] University of Science and Technology of China, Division of Life Sciences and Medicine, Intelligent Pathology InstituteHefei, China.
[Lin, Mengyu] University of Science and Technology of China, Division of Life Sciences and Medicine, Intelligent Pathology InstituteHefei, China.
[Li, Heng] University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of PathologyHefei, China.
[Chen, Jingjing] University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of PathologyHefei, China.
[Zhou, Wenchao] University of Science and Technology of China, Division of Life Sciences and Medicine, Intelligent Pathology InstituteHefei, China.
[He, Jie] Shandong University, School of MedicineJinan, China.
[Wu, Haibo] University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of PathologyHefei, China.
RP Wu, H (reprint author), University of Science and Technology of China, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Department of Pathology, Hefei, China.
EM wuhaibo@ustc.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609844
EP 1609855
DI 10.3389/pore.2021.1609844
PG 12
ER
PT J
AU Zhang, N
Liu, Y
Yang, H
Liang, M
Wang, X
Wang, M
Kong, J
Yuan, X
Zhou, F
AF Zhang, Ning
Liu, Yiwen
Yang, Hong
Liang, Mengxia
Wang, Xiaopeng
Wang, Min
Kong, Jinyu
Yuan, Xiang
Zhou, Fuyou
TI Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Esophageal squamous cell carcinoma; Fusobacterium nucleatum; Prognostic value; regulatory T cells; clinical significance
ID Esophageal squamous cell carcinoma; Fusobacterium nucleatum; Prognostic value; regulatory T cells; clinical significance
AB A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. Fusobacterium nucleatum (F. nucleatum) is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of regulatory T cell (Tregs) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. Tregs are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because F. nucleatum can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between F. nucleatum infection and Tregs infiltration. Therefore, we propose the view that chronic infection of F. nucleatum may provide favorable conditions for long-term colonization of itself by recruiting Tregs and suppressing the immune response. At the same time, the massive enrichment of Treg may also weaken the immune response and assist in the long-term colonization of F. nucleatum. We analyzed the correlation between F. nucleatum infection with the clinicopathological characteristics and survival prognosis of the patients. F. nucleatum infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and F. nucleatum infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the F. nucleatum infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of F. nucleatum infection. In turn, F. nucleatum infection and colonization may weaken the antitumor immune response through Treg enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.
C1 [Zhang, Ning] The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang Tumor HospitalAnyang, China.
[Liu, Yiwen] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Yang, Hong] Henan University of Science and Technology, School of PELuoyang, China.
[Liang, Mengxia] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Wang, Xiaopeng] The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang Tumor HospitalAnyang, China.
[Wang, Min] The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang Tumor HospitalAnyang, China.
[Kong, Jinyu] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Yuan, Xiang] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Zhou, Fuyou] The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang Tumor HospitalAnyang, China.
RP Zhou, F (reprint author), The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang Tumor Hospital, Anyang, China.
EM ayzhoufuyou@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609846
EP 1609854
DI 10.3389/pore.2021.1609846
PG 9
ER
PT J
AU Ma, W
Li, W
Xu, L
Liu, L
Xia, Y
Yang, L
Da, M
AF Ma, Weijun
Li, Weidong
Xu, Lei
Liu, Lu
Xia, Yu
Yang, Liping
Da, Mingxu
TI Identification of a Gene Prognostic Model of Gastric Cancer Based on Analysis of Tumor Mutation Burden
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; gastric cancer; TCGA; immune infiltration; tumor mutation burden
ID prognosis; gastric cancer; TCGA; immune infiltration; tumor mutation burden
AB Introduction: Gastric cancer is one of the most common cancers. Although some progress has been made in the treatment of gastric cancer with the improvement of surgical methods and the application of immunotherapy, the prognosis of gastric cancer patients is still unsatisfactory. In recent years, there has been increasing evidence that tumor mutational load (TMB) is strongly associated with survival outcomes and response to immunotherapy. Given the variable response of patients to immunotherapy, it is important to investigate clinical significance of TMB and explore appropriate biomarkers of prognosis in patients with gastric cancer (GC). Material and Methods: All data of patients with gastric cancer were obtained from the database of The Cancer Genome Atlas (TCGA). Samples were divided into two groups based on median TMB. Differently expressed genes (DEGs) between the high- and low- TMB groups were identified and further analyzed. We identified TMB-related genes using Lasso, univariate and multivariate Cox regression analysis and validated the survival result of 11 hub genes using Kaplan-Meier Plotter. In addition, “CIBERSORT” package was utilized to estimate the immune infiltration. Results: Single nucleotide polymorphism (SNP), C > T transition were the most common variant type and single nucleotide variant (SNV), respectively. Patients in the high-TMB group had better survival outcomes than those in the low-TMB group. Besides, eleven TMB-related DEGs were utilized to construct a prognostic model that could be an independent risk factor to predict the prognosis of patients with GC. What’s more, the infiltration levels of CD4+ memory-activated T cells, M0 and M1 macrophages were significantly increased in the high-TMB group compared with the low-TMB group. Conclusions: Herein, we found that patients with high TMB had better survival outcomes in GC. In addition, higher TMB might promote immune infiltration, which could provide new ideas for immunotherapy.
C1 [Ma, Weijun] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Li, Weidong] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
[Xu, Lei] Gansu Provincial Hospital, Department of Surgical OncologyLanzhou, China.
[Liu, Lu] Gansu Provincial Hospital, Department of Surgical OncologyLanzhou, China.
[Xia, Yu] Gansu Provincial Hospital, Department of Surgical OncologyLanzhou, China.
[Yang, Liping] Gansu Provincial Hospital, Department of Surgical OncologyLanzhou, China.
[Da, Mingxu] Ningxia Medical University, College of Clinical MedicineYinchuan, China.
RP Da, M (reprint author), Ningxia Medical University, College of Clinical Medicine, Yinchuan, China.
EM hxdamingxu@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609852
EP 1609866
DI 10.3389/pore.2021.1609852
PG 15
ER
PT J
AU Diao, B
Yang, P
AF Diao, Bowen
Yang, Ping
TI Comprehensive Analysis of the Expression and Prognosis for Laminin Genes in Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ovarian cancer; metastasis; laminins; cancer prognosis; bioinformatical analysis
ID ovarian cancer; metastasis; laminins; cancer prognosis; bioinformatical analysis
AB Survival is low in ovarian cancer (OC). Most OC patients demonstrate advanced metastases, and recurrence is common. Dysregulation of laminin interactions is associated with cancer development. However, it is unknown whether laminin subunits can be considered as biomarkers for OC diagnosis, prognosis, and treatment. We used cBioPortal, GEO, ONCOMINE, GEPIA, Human Protein Atlas, Kaplan-Meier Plotter, TIMER, and Metascape to determine the associations among laminin expression, prognosis, and immune cell infiltration in OC. LAMA5, LAMB3, and LAMC2 mRNAs and LAMA3, LAMB1/ B2/B3, and LAMC1/C2 proteins were overexpressed in OC tissues compared with normal ovaries. LAMA4, LAMB1, and LAMC1 mRNA upregulation was positively correlated with worse overall survival (OS) and progression-free survival (PFS) in OC. Elevated LAMA2 and LAMC2 mRNA expression levels were related to better PFS or OS, respectively. The results speculated that LAMA5 could potentially be a good prognostic factor in OC. Its expression proves valuable for predicting OS in patients diagnosed with stage Ⅳ and grade 3 OC and PFS in patients diagnosed with all OC stages or grades. LAMB3 and LAMC2 expression was correlated with platinum resistance development. ROC analysis of laminins in OC sets revealed that LAMA2/A4/A5, LAMB1/B2/B3, and LAMC2 could be used to differentiate between malignant tumors and non-neoplastic tissues. LAMA1/A5 and LAMC1 were significantly and negatively correlated with various tumor immune infiltrates (TILs), especially with dendritic cells, CD8+ T cells or neutrophil. LAMA4 and LAMB1 might be associated with tumor purity in OC. Overall, LAMA5 and LAMC1 could help predict OC survival and diagnosis and might be deemed important OC oncogenes.
C1 [Diao, Bowen] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Yang, Ping] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
RP Yang, P (reprint author), Shihezi University, School of Medicine, First Affiliated Hospital, Department of Gynecology, Shihezi, China.
EM pingy2018@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609855
EP 1609867
DI 10.3389/pore.2021.1609855
PG 13
ER
PT J
AU Jain, D
Guleria, P
Singh, V
Parshad, R
Kumar, S
Gaiser, T
Kurz, K
Ott, G
Porubsky, S
Preissler, G
Sauer, Ch
Scholch, S
Strobel, P
Hielscher, Th
Marx, A
Popovic, Z
AF Jain, Deepali
Guleria, Prerna
Singh, Varsha
Parshad, Rajinder
Kumar, Sunil
Gaiser, Timo
Kurz, S. Katrin
Ott, German
Porubsky, Stefan
Preissler, Gerhard
Sauer, G. Christian
Scholch, Sebastian
Strobel, Philipp
Hielscher, Thomas
Marx, Alexander
Popovic, V. Zoran
TI GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epidemiology; thymoma; GTF2I mutation; myasthenia gravis; racial-ethnic factors
ID epidemiology; thymoma; GTF2I mutation; myasthenia gravis; racial-ethnic factors
AB Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany (n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar (p = 0.1622), Indian patients were strikingly younger (p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis (p = 0.0005) than the German patients. In patients with known MG status (n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group (p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation.
C1 [Jain, Deepali] All India Institute of Medical Sciences, Department of PathologyNew Delhi, India.
[Guleria, Prerna] All India Institute of Medical Sciences, Department of PathologyNew Delhi, India.
[Singh, Varsha] All India Institute of Medical Sciences, Department of PathologyNew Delhi, India.
[Parshad, Rajinder] All India Institute of Medical Sciences, Department of SurgeryNew Delhi, India.
[Kumar, Sunil] All India Institute of Medical Sciences, Dr BRA Institute-Rotary Cancer Hospital, Department of Surgical OncologyNew Delhi, India.
[Gaiser, Timo] University of Heidelberg, University Medical Centre Mannheim, Institute of PathologyMannheim, Germany.
[Kurz, S. Katrin] Dr. Margarete Fischer-Bosch Institute for Clinical PharmacologyStuttgart, Germany.
[Ott, German] Dr. Margarete Fischer-Bosch Institute for Clinical PharmacologyStuttgart, Germany.
[Porubsky, Stefan] University of Heidelberg, University Medical Centre Mannheim, Institute of PathologyMannheim, Germany.
[Preissler, Gerhard] Robert-Bosch-Krankenhaus, Schillerhohe Clinics, Department of Thoracic SurgeryGerlingen, Germany.
[Sauer, G. Christian] University of Heidelberg, University Medical Centre Mannheim, Institute of PathologyMannheim, Germany.
[Scholch, Sebastian] University of Heidelberg, University Medical Centre Mannheim, Department of SurgeryMannheim, Germany.
[Strobel, Philipp] University of Gottingen, Institute of PathologyGottingen, Germany.
[Hielscher, Thomas] German Cancer Research Center (DKFZ), Department of BiostatisticsHeidelberg, Germany.
[Marx, Alexander] University of Heidelberg, University Medical Centre Mannheim, Institute of PathologyMannheim, Germany.
[Popovic, V. Zoran] University of Heidelberg, University Medical Centre Mannheim, Institute of PathologyMannheim, Germany.
RP Jain, D (reprint author), All India Institute of Medical Sciences, Department of Pathology, New Delhi, India.
EM deepalijain76@gmail.com
CR Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol, 2015, 10(9):1243–60., DOI 10.1097/ jto.0000000000000630
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609858
EP 1609867
DI 10.3389/pore.2021.1609858
PG 10
ER
PT J
AU An, Y
Zhou, J
Lin, G
Wu, H
Cong, L
Li, Y
Qiu, X
Shi, W
AF An, Yang
Zhou, Jiaolin
Lin, Guole
Wu, Huanwen
Cong, Lin
Li, Yunhao
Qiu, Xiaoyuan
Shi, Weikun
TI Clinicopathological and Molecular Characteristics of Colorectal Signet Ring Cell Carcinoma: A Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE colorectal cancer; clinicopathology; signet ring cell carcinoma; molecular features; review
ID colorectal cancer; clinicopathology; signet ring cell carcinoma; molecular features; review
AB Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and indepth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/β-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the “epithelial-mesenchymal transition (EMT) process” and the “stem cell properties”, including RNF43, CDH1, and SMAD4, as well as the related TGF-β signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI+/CIMP+/BRAF+/CD3+/PD-L1+ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.
C1 [An, Yang] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Zhou, Jiaolin] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Lin, Guole] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Wu, Huanwen] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of PathologyBeijing, China.
[Cong, Lin] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Li, Yunhao] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Qiu, Xiaoyuan] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
[Shi, Weikun] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General SurgeryBeijing, China.
RP Zhou, J (reprint author), Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of General Surgery, Beijing, China.
EM conniezhjl@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609859
EP 1609871
DI 10.3389/pore.2021.1609859
PG 13
ER
PT J
AU Oh, ES
Oh, YM
An, YJ
Lee, HJ
Sohn, ST
Bae, MJ
Choi, MG
Kim, KM
AF Oh, Eun Sung
Oh, Yun Mi
An, Yeong Ji
Lee, Ho Jun
Sohn, Sung Tae
Bae, Moon Jae
Choi, Min-Gew
Kim, Kyoung-Mee
TI Prognostic Value of Highly Expressed Type VII Collagen (COL7A1) in Patients With Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; gastric cancer; tumor microenvironment; type VII collagen (COL7A1); distant metastasis
ID biomarker; prognosis; gastric cancer; tumor microenvironment; type VII collagen (COL7A1); distant metastasis
AB Collagen is a major component in the tumor microenvironment. This study reveals a novel biomarker candidate, type VII collagen (COL7A1), in patients with gastric cancer. To identify genes differentially expressed in gastric cancer tissue, we analyzed cancerous (n = 20) and noncancerous tissues (n = 13) using a DNA microarray. To perform immunohistochemistry and validate the upregulation of COL7A1 expression, we collected 200 more gastric cancer tissues and 100 normal gastric tissues from 200 randomly selected patients who underwent gastrectomy for gastric cancer between January 2010 and December 2013. The correlations between COL7A1 expression and clinicopathological parameters and patients’ overall survival (OS) were analyzed. In the microarray, COL7A1 was upregulated in gastric cancer tissue compared with normal tissue. In the immunohistochemistry study, COL7A1 was more highly expressed in cancer tissue than in normal tissue (p = 0.001). Patients with intracellular COL7A1 expression had significantly poorer five-year OS than those with only extracellular expression (41.5 versus 69.7%, p = 0.001), and the site of expression was an independent prognostic factor of OS (hazard ratio 2.00, 95% CI 1.26–3.16, p = 0.003). Also, we found a significant association between the COL7A1 immunohistochemistry score and distant metastasis (high versus low, odds ratio 4.45, 95% CI 1.40–14.16, p = 0.011). The site and total immunohistochemistry score of COL7A1 expression in gastric cancer showed prognostic significance for OS and distant metastasis, respectively. COL7A1 could be a novel biomarker with diagnostic and therapeutic value.
C1 [Oh, Eun Sung] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Oh, Yun Mi] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[An, Yeong Ji] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Lee, Ho Jun] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Sohn, Sung Tae] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Bae, Moon Jae] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Choi, Min-Gew] Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of SurgerySeoul, South Korea.
[Kim, Kyoung-Mee] Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of PathologySeoul, South Korea.
RP Choi, MG (reprint author), Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Department of Surgery, Seoul, South Korea.
EM mingew.choi@samsung.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609860
EP 1609870
DI 10.3389/pore.2021.1609860
PG 11
ER
PT J
AU Kopinska, JA
Koclega, A
Wozniczka, K
Helbig, G
AF Kopinska, J Anna
Koclega, Anna
Wozniczka, Krzysztof
Helbig, Grzegorz
TI Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Hodgkin lymphoma; allogeneic stem cell transplantation; autologous stem cell transplantation; chemosensitivity; outcome
ID Hodgkin lymphoma; allogeneic stem cell transplantation; autologous stem cell transplantation; chemosensitivity; outcome
AB Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach. Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting. Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020. Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%. Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.
C1 [Kopinska, J Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow TransplantationKatowice, Poland.
[Koclega, Anna] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow TransplantationKatowice, Poland.
[Wozniczka, Krzysztof] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow TransplantationKatowice, Poland.
[Helbig, Grzegorz] Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow TransplantationKatowice, Poland.
RP Helbig, G (reprint author), Medical University of Silesia, School of Medicine in Katowice, Department of Hematology and Bone Marrow Transplantation, Katowice, Poland.
EM ghelbig@o2.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609867
EP 1609873
DI 10.3389/pore.2021.1609867
PG 7
ER
PT J
AU Liu, Sh
Cai, Y
Sheng, J
Zhang, X
AF Liu, Shui
Cai, Yan
Sheng, Jiyao
Zhang, Xuewen
TI Screening and Validation ofIndependent Predictors of PoorSurvival in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; pancreatic cancer; the cancer genome atlas; tetraspanin-1; erb-b2 receptor tyrosine kinase 3; gene expression omnibus
ID prognosis; pancreatic cancer; the cancer genome atlas; tetraspanin-1; erb-b2 receptor tyrosine kinase 3; gene expression omnibus
AB Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It’s necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student’s t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.
C1 [Liu, Shui] Jilin University, The Second Hospital of Jilin University, Department of Hepatobiliary and Pancreatic SurgeryChangchun, China.
[Cai, Yan] Jilin University, Hospital of StomatologyChangchun, China.
[Sheng, Jiyao] Jilin University, The Second Hospital of Jilin University, Department of Hepatobiliary and Pancreatic SurgeryChangchun, China.
[Zhang, Xuewen] Jilin University, The Second Hospital of Jilin University, Department of Hepatobiliary and Pancreatic SurgeryChangchun, China.
RP Sheng, J (reprint author), Jilin University, The Second Hospital of Jilin University, Department of Hepatobiliary and Pancreatic Surgery, Changchun, China.
EM shengjiyao@jlu.edu.cn
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, and Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a Cancer J clinicians, 2018, 68(6):394–424., DOI 10.3322/caac.21492
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Cui M, Yao X, Lin Y, Zhang D, Cui R, and Zhang X. Interactive Functions of microRNAs in the miR-23a-27a-24-2 Cluster and the Potential for Targeted Therapy in Cancer. J Cel Physiol, 2020, 235(1):6–16., DOI 10.1002/jcp.28958
Hou J, Li X, and Xie KP. Coupled Liquid Biopsy and Bioinformatics for Pancreatic Cancer Early Detection and Precision Prognostication. Mol Cancer, 2021, 20(1):34., DOI 10.1186/s12943-021-01309-7
Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, et al. FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt. Cancer cell, 2009, 16(3):259–66., DOI 10.1016/j.ccr.2009.07.016
Donahue TR, Tran LM, Hill R, Li Y, Kovochich A, Calvopina JH, et al. Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer. Clin Cancer Res, 2012, 18(5):1352–63., DOI 10.1158/1078-0432.ccr-11-1539
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies. Nucleic Acids Res, 2015, 43(7):e47., DOI 10.1093/nar/gkv007
Kolde R, and Kolde MR. Package ‘pheatmap’. R Package, 2015, 1(7):790.
Yu G, Li F, Qin Y, Bo X, Wu Y, and Wang S. GOSemSim: an R Package for Measuring Semantic Similarity Among GO Terms and Gene Products. Bioinformatics, 2010, 26(7):976–8., DOI 10.1093/bioinformatics/ btq064
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609868
EP 1609876
DI 10.3389/pore.2021.1609868
PG 9
ER
PT J
AU Yang, H
Wang, K
Li, Sh
Li, Y
Yuan, L
AF Yang, Hui
Wang, Kunlun
Li, Shenglei
Li, Yan
Yuan, Ling
TI The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; NSCLC; stage IIIA/N2; postoperative radiotherapy; prognostic factors
ID EGFR; NSCLC; stage IIIA/N2; postoperative radiotherapy; prognostic factors
AB Background: The treatment choice for completely resected stage IIIA/N2 non-small cell lung cancer (NSCLC) patients is still controversial now. Our study aims to identify potential prognostic factors in stage IIIA/N2 NSCLC patients with complete surgical resection and postoperative chemotherapy. Methods: In this study, we screened the stage IIIA/N2 NSCLC patients diagnosed in the Affiliated Cancer Hospital of Zhengzhou University from 2015 to 2019. Completely resected patients with postoperative chemotherapy (PCT) were enrolled. The univariate and multivariate COX proportional hazards regression analyses were used to identify the prognostic factors. The Kaplan-Meier survival curve was used to compare the disease-free survival (DFS) and overall survival (OS) in the subgroup analyses. Results: 180 patients were collected, including 142 patients with PCT treatment alone and 38 patients with postoperative radiotherapy (PORT) treatment. The median DFS was 17.8months (95% CI: 16.5–19.1months) and the median OS was 50.6months (47.4–53.9months) in all the patients. The median DFS of the PORT group was significantly longer than the PCT group (38.7 vs 16.7months, p < 0.001). Epidermal growth factor receptor (EGFR) mutation-positive patients had a worse DFS compared with EGFR mutation-negative patients (16.8 vs 18.0months, p = 0.032). Possible prognostic factors were evaluated through univariateCOX regression analysis. The furthermultivariate COX regression analysis showed that patients with PORT(HR: 0.318,95%CI: 0.185–0.547, p < 0.001), EGFRmutation-negative (HR: 0.678, 95% CI: 0.492–0.990, p = 0.044), T1 (HR: 0.661, 95% CI: 0.472–0.925, p = 0.016), and lobectomy (HR: 0.423, 95% CI: 0.191–0.935, p = 0.034), had better DFS. The only independent prognostic factor of OS was the type of surgery (p = 0.013). Conclusion: PORT might improve the DFS of stage IIIA/N2 NSCLC patients with complete surgical resection and PCT, but it cannot increase OS. Besides, EGFR mutation status, T stage, and type of surgery are possible independent prognostic factors for DFS, and type of surgery is associated with OS. These factors remain to be clarified in further studies.
C1 [Yang, Hui] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Wang, Kunlun] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Li, Shenglei] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Li, Yan] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Yuan, Ling] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
RP Yuan, L (reprint author), The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation Oncology, Zhengzhou, China.
EM HNHNYL@126.com
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Corso CD, Rutter CE, Wilson LD, Kim AW, Decker RH, and Husain ZA. Reevaluation of the Role of Postoperative Radiotherapy and the Impact of Radiation Dose for Non-small-cell Lung Cancer Using the National Cancer Database. J Thorac Oncol, 2015, 10(1):148–55., DOI 10.1097/ JTO.0000000000000406
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609898
EP 1609902
DI 10.3389/pore.2021.1609898
PG 5
ER
PT J
TI Pathological Features in 100 Deceased Patients With COVID-19 in Correlation With Clinical and Laboratory Data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE histological subtype; COVID-19; pathological features; large cohort; morphology
ID histological subtype; COVID-19; pathological features; large cohort; morphology
AB Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 postmortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609900
EP 1609911
DI 10.3389/pore.2021.1609900
PG 12
ER
PT J
AU Xu, F
Tian, D
Shi, X
Sun, K
Chen, Y
AF Xu, Fangfang
Tian, Dandan
Shi, Xiaoyang
Sun, Kai
Chen, Yuqing
TI Analysis of the Expression and Prognostic Potential of a Novel Metabolic Regulator ANGPTL8/ Betatrophin in Human Cancers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE inflammation; prognostic biomarker; ANGPTL8/betatrophin; differential expression analysis; lipid metabolism; glucose homeostasis; Akt signaling
ID inflammation; prognostic biomarker; ANGPTL8/betatrophin; differential expression analysis; lipid metabolism; glucose homeostasis; Akt signaling
AB The angiopoietin-like protein (ANGPTL) family members, except for the novel atypical member ANGPTL8/betatrophin, have been reported to participate in angiogenesis, inflammation and cancer. ANGPTL8/betatrophin is a metabolic regulator that is involved in lipid metabolism and glucose homeostasis. However, little is known about the expression and prognostic value of ANGPTL8/betatrophin in human cancers. In this study, we first conducted detailed analyses of ANGPTL8/betatrophin expression in cancer/normal samples via the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), DriverDBv3, ENCORI and UALCAN databases. ANGPTL8/ betatrophin showed high tissue specificity (enriched in the liver) and cell-type specificity (enriched in HepG2 and MCF7 cell lines). More than one databases demonstrated that the gene expression of ANGPTL8/betatrophin was significantly lower in cholangiocarcinoma (CHOL), breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), and significantly higher in kidney renal clear cell carcinoma (KIRC) compared with that in normal samples. However, the protein expression of ANGPTL8/betatrophin displayed opposite results in clear cell renal cell carcinoma (ccRCC)/KIRC. Based on the expression profiles, the prognostic value was evaluated with the GEPIA, DriverDBv3, Kaplan Meier plotter and ENCORI databases. Two or more databases demonstrated that ANGPTL8/betatrophin significantly affected the survival of KIRC, uterine corpus endometrial carcinoma (UCEC), pheochromocytoma and paraganglioma (PCPG) and sarcoma (SARC); patients with PCPG and SARC may benifit from high ANGPTL8/betatrophin expression while high ANGPTL8/betatrophin expression was associated with poor prognosis in KIRC and UCEC. Functional analyses with the GeneMANIA, Metascape and STRING databases suggested that ANGPTL8/betatrophin was mainly involved in lipid homeostasis, especially triglyceride and cholesterol metabolism; glucose homeostasis, especially insulin resistance; AMPK signaling pathway; PI3K/Akt signaling pathway; PPAR signaling pathway; mTOR signaling pathway; HIF-1 signaling pathway; autophagy; regulation of inflammatory response. ANGPTL8/betatrophin may be a promising prognostic biomarker and therapeutic target, thus providing evidence to support further exploration of its role in defined human cancers.
C1 [Xu, Fangfang] Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Clinical Medical Research CenterZheng Zhou, China.
[Tian, Dandan] Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Department of HypertensionZheng Zhou, China.
[Shi, Xiaoyang] Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Department of EndocrinologyZheng Zhou, China.
[Sun, Kai] Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Department of HematologyZheng Zhou, China.
[Chen, Yuqing] Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Department of HematologyZheng Zhou, China.
RP Sun, K (reprint author), Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Department of Hematology, Zheng Zhou, China.
EM sunkai@cellscience.org
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DiDonato JA, Mercurio F, and Karin M. NF-κB and the Link between Inflammation and Cancer. Immunol Rev, 2012, 246(246):379–400., DOI 10.1111/j.1600-065X.2012.01099.x
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609914
EP 1609928
DI 10.3389/pore.2021.1609914
PG 15
ER
PT J
TI Late Radiation–Related Toxicities in Patients Treated for Early-Stage Cervical Carcinoma by Surgery and Adjuvant Radiotherapy: A Retrospective Imaging Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; toxicity; radiation-induced tumor; complication; bone; comorbidity
ID cancer; toxicity; radiation-induced tumor; complication; bone; comorbidity
AB Surgical treatment is preferred therapy of early-stage cervical carcinoma. In the risk of cancer recurrence surgery is often followed by adjuvant radiotherapy. In our retrospective study we aimed at identifying late (≥6 months) and very late (≥5 years) radiation adverse effects on imaging scans as CT, PET/CT and MRI in patients who underwent successful treatment for cervical carcinoma by radical surgery combined with radiotherapy ± chemotherapy. We correlated imaging results with clinical manifestations. We selected young and middle-aged patients with long life expectancy, as late radiation-related toxicities may significantly affect their quality of life. Patients were selected from those who were primary diagnosed and treated between the years 1987–2011 and regularly visited our Oncology department in years 2011–2012. Following inclusion criteria were applied: age ≤55 years at diagnosis, clinical follow-up ≥5 years and at least one tomography scan ≥3 years after finished treatment. One hundred and three subjects were reviewed: 73 patients met all inclusion criteria, while 30 patients fulfilled the inclusion criteria except for available tomography scan ≥3 years after therapy. The mean imaging follow-up was 11.2 ± 7.6 years and the mean clinical follow-up was 15.0 ± 6.9 years. In 20 (27%) subjects 27 cases grade I radiation-related toxicities were found; 9 (33%) of those 27 cases were clinically silent. In 14 (19%) females only grade I toxicities were observed. Grade III-IV toxicities were found in 5 (6.8%) subjects. No grade V toxicities were observed. We concluded that severe late side effects caused by radiotherapy were exceedingly rare in females successfully treated for early-stage cervical carcinoma, only 1 bilateral osteonecrosis, 2 cases of ileus, and 2 potentially radiation-induced tumors were found. The majority of radiation-related comorbidities found on imaging scans were clinically silent.
CR Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clin, 2021, 71:209–49., DOI 10.3322/caac.21660
Bhatla N, Aoki D, Sharma DN, and Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynecol Obstet, 2018, 143(Suppl. 2):22–36., DOI 10.1002/ijgo.12611
Gaffney DK. Optimal therapy for IB2 and IIA2 cervical cancer: surgery or chemoradiotherapy? J Gynecol Oncol, 2012, 23(4):207–20., DOI 10.3802/ jgo.2012.23.4.207
Hricak H, Gatsonis C, Chi DS, Amendola MA, Brandt K, Schwartz LH, et al. Role of Imaging in Pretreatment Evaluation of Early Invasive Cervical Cancer: Results of the Intergroup Study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183. Jco, 2005, 23(36): 9329–37., DOI 10.1200/jco.2005.02.0354
Kraljevic Z, Viskovic K, Ledinsky M, Zadravec D, Grbavac I, Bilandzija M, et al. Primary uterine cervical cancer: correlation of preoperative magnetic resonance imaging and clinical staging, FIGO, with histopathology findings. Coll Antropol, 2013, 37(2):561–8.
Viswanathan AN, Lee LJ, Eswara JR, Horowitz NS, Konstantinopoulos PA, Mirabeau-Beale KL, et al. Complications of pelvic radiation in patients treated for gynecologic malignancies. Cancer, 2014, 120(24):3870–83., DOI 10.1002/ cncr.28849
Singh GK, Yadav V, Singh P, and Bhowmik KT. Radiation-Induced Malignancies Making Radiotherapy a "Two-Edged Sword": A Review of Literature. World J Oncol, 2017, 8(1):1–6., DOI 10.14740/wjon996w
Vale C, Tierney JF, Stewart LA, Brady M, Dinshaw K, Jakobsen A, et al. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. Jco, 2008, 26(35):5802–12., DOI 10.1200/jco.2008.16.4368
Malikova H, Burghardtova M, Fejfarova K, Nadova K, and Weichet J. Advanced cervical cancer in young women: imaging study of late and very late radiation-related side effects after successful treatment by combined radiotherapy. Quant Imaging Med Surg, 2021, 11(1):21–31., DOI 10.21037/ qims-20-553
Yuce Sari S, Guler OC, Gultekin M, Onal HC, and Yildiz F. Adjuvant Small Pelvic Radiotherapy in Patients with Cervical Cancer Having Intermediate Risk Factors Only - Is it Sufficient? Oncol Res Treat, 2017, 40(9):523–7., DOI 10.1159/000476037
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Yu H, Zhang L, Du X, and Sheng X. Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy in early-stage cervical cancer patients with intermediate risk factors. Ott, 2016, Vol. 9:7331–5., DOI 10.2147/ott.s107146
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609915
EP 1609923
DI 10.3389/pore.2021.1609915
PG 9
ER
PT J
AU Galffy, G
Vastag, A
Bogos, K
Kiss, Z
Ostoros, Gy
Muller, V
Urban, L
Bittner, N
Sarosi, V
Polanyi, Z
Nagy-Erdei, Zs
Daniel, A
Knollmajer, K
Varnai, M
Szegner, P
Voko, Z
Nagy, B
Horvath, K
Rokszin, Gy
Abonyi-Toth, Zs
Pozsgai, E
Barcza, Zs
Moldvay, J
Tamasi, L
AF Galffy, Gabriella
Vastag, Aladar
Bogos, Krisztina
Kiss, Zoltan
Ostoros, Gyula
Muller, Veronika
Urban, Laszlo
Bittner, Nora
Sarosi, Veronika
Polanyi, Zoltan
Nagy-Erdei, Zsofia
Daniel, Andrea
Knollmajer, Kata
Varnai, Mate
Szegner, Peter
Voko, Zoltan
Nagy, Balazs
Horvath, Krisztian
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Pozsgai, Eva
Barcza, Zsofia
Moldvay, Judit
Tamasi, Lilla
TI Significant Regional Differences in Lung Cancer Incidence in Hungary: Epidemiological Study Between 2011 and 2016
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epidemiology; Hungary; mortality; lung cancer; incidence; Hungarian regions
ID epidemiology; Hungary; mortality; lung cancer; incidence; Hungarian regions
AB Objective: Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions. Methods: This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions. Results: The highest incidence rate in males was recorded in Northern Hungary (146.8/ 100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (−20.0%; p = 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence (p = 0.006 and p = 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females. Conclusion: This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences.
C1 [Galffy, Gabriella] County Hospital of PulmonologyTorokbalint, Hungary.
[Vastag, Aladar] MSD Pharma Hungary Kft.Budapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute for TB and Pulmonology, Department of PulmonologyBudapest, Hungary.
[Kiss, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Ostoros, Gyula] County Hospital of PulmonologyTorokbalint, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Urban, Laszlo] Matrahaza Healthcare Center and University Teaching Hospital, Department of PulmonologyMatrahaza, Hungary.
[Bittner, Nora] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of Medicine, Department of PulmonologyPecs, Hungary.
[Polanyi, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy-Erdei, Zsofia] MSD Pharma Hungary Kft.Budapest, Hungary.
[Daniel, Andrea] MSD Pharma Hungary Kft.Budapest, Hungary.
[Knollmajer, Kata] MSD Pharma Hungary Kft.Budapest, Hungary.
[Varnai, Mate] MSD Pharma Hungary Kft.Budapest, Hungary.
[Szegner, Peter] MSD Pharma Hungary Kft.Budapest, Hungary.
[Voko, Zoltan] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Nagy, Balazs] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Horvath, Krisztian] Eotvos Lorand University, Department of Health Policy and Health EconomicsBudapest, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Pozsgai, Eva] University of Pecs, Medical School, Department of Primary Health CarePecs, Hungary.
[Barcza, Zsofia] Syntesia LtdBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Department of Tumor BiologyBudapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
RP Kiss, Z (reprint author), MSD Pharma Hungary Kft., Budapest, Hungary.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609916
EP 1609926
DI 10.3389/pore.2021.1609916
PG 11
ER
PT J
TI Retraction: Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 Through the Wnt Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB Song, X., Wang, Q. and Huo, R. Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 Through the Wnt Signaling Pathway. Pathol. Oncol. Res. 25, 377–389 (2019). doi: https://doi.org/10.1007/s12253-017-0334-z
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609917
EP 1609917
DI 10.3389/pore.2021.1609917
PG 1
ER
PT J
AU Radeczky, P
Moldvay, J
Fillinger, J
Szeitz, B
Ferencz, B
Boettiger, K
Rezeli, M
Bogos, K
Renyi-Vamos, F
Hoetzenecker, K
Hegedus, B
Megyesfalvi, Zs
Dome, B
AF Radeczky, Peter
Moldvay, Judit
Fillinger, Janos
Szeitz, Beata
Ferencz, Bence
Boettiger, Kristiina
Rezeli, Melinda
Bogos, Krisztina
Renyi-Vamos, Ferenc
Hoetzenecker, Konrad
Hegedus, Balazs
Megyesfalvi, Zsolt
Dome, Balazs
TI Bone-Specific Metastasis Pattern of Advanced-Stage Lung Adenocarcinoma According to the Localization of the Primary Tumor
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; adenocarcinoma; metastasis pattern; bone metastasis; tumor localization
ID lung cancer; adenocarcinoma; metastasis pattern; bone metastasis; tumor localization
AB Background: Patients with advanced-stage lung adenocarcinoma (LADC) often develop distant metastases in the skeletal system. Yet, the bone-specific metastasis pattern is still controversial. We, therefore, aimed to examine how the primary tumor location affects bone specificity and survival in LADC patients diagnosed with skeletal metastases. Methods: In total, 209 bone-metastatic Caucasian LADC patients from two thoracic centers were included in this study. Focusing on the specific location of primary tumors and bone metastatic sites, clinicopathological variables were included in a common database and analyzed retrospectively. Skeletal metastases were diagnosed according to the contemporary diagnostic guidelines and confirmed by bone scintigraphy. Besides region- and side-specific localization, primary tumors were also classified as central or peripheral tumors based on their bronchoscopic visibility. Results: The most common sites for metastasis were the spine (n = 103) and the ribs (n = 60), followed by the pelvis (n = 36) and the femur (n = 22). Importantly, femoral (p = 0.022) and rib (p = 0.012) metastases were more frequently associated with peripheral tumors, whereas centrally located LADCs were associated with humeral metastases (p = 0.018). Moreover, we deduced that left-sided tumors give rise to skull metastases more often than right-sided primary tumors (p = 0.018). Of note, however, the localization of the primary tumor did not significantly influence the type of affected bones. Multivariate Cox regression analysis adjusted for clinical parameters demonstrated that central localization of the primary tumor was an independent negative prognostic factor for overall survival (OS). Additionally, as expected, both chemotherapy and bisphosphonate therapy conferred a significant benefit for OS. Conclusion: The present study demonstrates unique bone-specific metastasis patterns concerning primary tumor location. Peripherally located LADCs are associated with rib and femoral metastases and improved survival outcomes. Our findings might contribute to the development of individualized follow-up strategies in bone-metastatic LADC patients and warrant further clinical investigations on a larger sample size.
C1 [Radeczky, Peter] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
[Moldvay, Judit] Hungarian Academy of Sciences - Semmelweis University, MTA-SE NAP, Brain Metastasis Research GroupBudapest, Hungary.
[Fillinger, Janos] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Szeitz, Beata] Semmelweis University, 1st Department of Internal MedicineBudapest, Hungary.
[Ferencz, Bence] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
[Boettiger, Kristiina] Medical University of Vienna, Department of Thoracic SurgeryVienna, Austria.
[Rezeli, Melinda] Lund University, Department of Biomedical EngineeringLund, Sweden.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Renyi-Vamos, Ferenc] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
[Hoetzenecker, Konrad] Medical University of Vienna, Department of Thoracic SurgeryVienna, Austria.
[Hegedus, Balazs] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Megyesfalvi, Zsolt] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
[Dome, Balazs] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
RP Dome, B (reprint author), Orszagos Onkologiai Intezet, Mellkassebeszeti Osztaly, Budapest, Hungary.
EM balazs.dome@meduniwien.ac.at
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609926
EP 1609935
DI 10.3389/pore.2021.1609926
PG 10
ER
PT J
AU Khatun, M
Urpilainen, E
Ahtikoski, A
Arffman, R
Pasanen, A
Puistola, U
Tapanainen, J
Andersson, L
Butzow, R
Loukovaara, M
Piltonen, T
AF Khatun, Masuma
Urpilainen, Elina
Ahtikoski, Anne
Arffman, K. Riikka
Pasanen, Annukka
Puistola, Ulla
Tapanainen, S. Juha
Andersson, C. Leif
Butzow, Ralf
Loukovaara, Mikko
Piltonen, T. Terhi
TI Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE stanniocalcin-1; uterine cancer; type 2 diabetes mellitus; disease-specific survival; endometrioid carcinoma; metformin
ID stanniocalcin-1; uterine cancer; type 2 diabetes mellitus; disease-specific survival; endometrioid carcinoma; metformin
AB Stanniocalcin-1 (STC-1) is a glycoprotein hormone involved in diverse biological processes, including regulation of calcium phosphate homeostasis, cell proliferation, apoptosis, inflammation, oxidative stress responses, and cancer development. The role of STC-1 in endometrial cancer (EC) is yet to be elucidated. In this study, we investigated the protein expression pattern of STC-1 in a tissue microarray (TMA) cohort of hysterectomy specimens from 832 patients with EC. We then evaluated the prognostic value of STC-1 expression regarding the clinicopathologic features and patients survival over a period of 140 months. Our results revealed that in EC tissue samples, STC-1 is mainly localized in the endometrial epithelium, although some expression was also observed in the stroma. Decreased STC-1 expression was associated with factors relating to a worse prognosis, such as grade 3 endometrioid tumors (p = 0.030), deep myometrial invasion (p = 0.003), lymphovascular space invasion (p = 0.050), and large tumor size (p = 0.001). Moreover, STC-1 expression was decreased in tumors obtained from obese women (p = 0.014) and in women with diabetes mellitus type 2 (DMT2; p = 0.001). Interestingly, the data also showed an association between DNA mismatch repair (MMR) deficiency and weak STC-1 expression, specifically in the endometrial epithelium (p = 0.048). No association was observed between STC-1 expression and disease-specific survival. As STC-1 expression was particularly low in cases with obesity and DMT2 in the TMA cohort, we also evaluated the correlation between metformin use and STC-1 expression in an additional EC cohort that only included women with DMT2 (n = 111). The analysis showed no difference in STC-1 expression in either the epithelium or the stroma in women undergoing metformin therapy compared to metformin non-users. Overall, our data may suggest a favorable role for STC- 1 in EC behavior; however, further studies are required to elucidate the detailed mechanism and possible applications to cancer treatment.
C1 [Khatun, Masuma] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
[Urpilainen, Elina] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
[Ahtikoski, Anne] University of Oulu, Department of PathologyOulu, Finland.
[Arffman, K. Riikka] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
[Pasanen, Annukka] Helsinki University Central Hospital, Department of PathologyHelsinki, Finland.
[Puistola, Ulla] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
[Tapanainen, S. Juha] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
[Andersson, C. Leif] Helsinki University Central Hospital, Department of PathologyHelsinki, Finland.
[Butzow, Ralf] Helsinki University Central Hospital, Department of PathologyHelsinki, Finland.
[Loukovaara, Mikko] Helsinki University Hospital and University of Helsinki, Department of Obstetrics and GynaecologyHelsinki, Finland.
[Piltonen, T. Terhi] University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research UnitOulu, Finland.
RP Piltonen, T (reprint author), University of Oulu, Medical Research Center, Oulu University Hospital, Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Oulu, Finland.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609936
EP 1609944
DI 10.3389/pore.2021.1609936
PG 9
ER
PT J
AU Cerina, D
Matkovic, V
Katic, K
Lovasic, BI
Separovic, R
Canjko, I
Jaksic, B
Frobe, A
Plestina, S
Bajic,
Vrdoljak, E
AF Cerina, Dora
Matkovic, Visnja
Katic, Kristina
Lovasic, Belac Ingrid
Separovic, Robert
Canjko, Ivana
Jaksic, Blanka
Frobe, Ana
Plestina, Stjepko
Bajic, Zarko
Vrdoljak, Eduard
TI Precision Oncology in Metastatic Uterine Cancer; Croatian First-Year Experience of the Comprehensive Genomic Profiling in Everyday Clinical Practice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE targeted therapy; genomic profiling; uterine cancer; precision oncology; mutation
ID targeted therapy; genomic profiling; uterine cancer; precision oncology; mutation
AB Comprehensive genomic profiling (CGP) is gradually becoming an inevitable part of the everyday oncology clinical practice. The interpretation and optimal implementation of the results is one of the hot topics of modern-day oncology. According to the recent findings, uterine cancer harbors a high level of gene alterations but is still insufficiently explored. The primary goal of this project was to assess the proportion of patients with targetable mutations. Also, the aim was to define and emphasize potential opportunities as well as the problems we have faced in the first year of testing on the national level. We performed a multicentric, retrospective, nested cross-sectional analysis on the total population of Croatian patients with advanced/metastatic uterine cancer where the tumor CGP was performed during 2020. CGP of the tumor tissue of 32 patients revealed clinically relevant genomic alterations (CRGA) in 27 patients (84%) with a median of 3 (IQR 1-4) CRGA per patient. The most common CRGAs were those of phosphatide-inositol-3 kinases (PIK3) in 22 patients (69%), with 13/22 (59%) of those patients harboring PIK3CA mutation. The next most common CGRAs were ARID1A and PTEN mutations in 13 (41%) and 11 (34%) patients, respectively. Microsatellite status was determined as stable in 21 patients (66%) and highly unstable in 10 patients (31%). A high tumor mutational burden (≥10Muts/Mb) was reported in 12 patients (38%). CGP analysis reported some kind of targeted therapy for 28 patients (88%). CGP determined clinically relevant genomic alterations in the significant majority of patients with metastatic uterine cancer, defining it as a rich ground for further positioning and development of precision oncology.
C1 [Cerina, Dora] University of Split, School of Medicine, Clinical Hospital Center Split, Department of OncologySplit, Croatia.
[Matkovic, Visnja] University Hospital Center Zagreb, Department of Gynecologic OncologyZagreb, Croatia.
[Katic, Kristina] University Hospital Center Zagreb, Department of Gynecologic OncologyZagreb, Croatia.
[Lovasic, Belac Ingrid] University Hospital Center Rijeka, Department of Radiotherapy and OncologyRijeka, Croatia.
[Separovic, Robert] Sestre Milosrdnice University Hospital Center, University Hospital for Tumors, Department of Medical Oncology, Division of Medical OncologyZagreb, Croatia.
[Canjko, Ivana] University Hospital Center Osijek, Department of Radiotherapy OncologyOsijek, Croatia.
[Jaksic, Blanka] Sestre Milosrdnice University Hospital Center, Department of Oncology and Nuclear MedicineZagreb, Croatia.
[Frobe, Ana] Sestre Milosrdnice University Hospital Center, Department of Oncology and Nuclear MedicineZagreb, Croatia.
[Plestina, Stjepko] University Hospital Center Zagreb and Zagreb Medical School, Department of Medical OncologyZagreb, Croatia.
[Bajic, Zarko] University Psychiatric Hospital “Sveti Ivan”, Research Unit “Dr. Mirko Grmek”Zagreb, Croatia.
[Vrdoljak, Eduard] University of Split, School of Medicine, Clinical Hospital Center Split, Department of OncologySplit, Croatia.
RP Vrdoljak, E (reprint author), University of Split, School of Medicine, Clinical Hospital Center Split, Department of Oncology, Split, Croatia.
EM edo.vrdoljak@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609963
EP 1609970
DI 10.3389/pore.2021.1609963
PG 8
ER
PT J
AU Zhang, C
Qian, J
Wu, Y
Zhu, Z
Yu, W
Gong, Y
Li, X
He, Z
Zhou, L
AF Zhang, Cuijian
Qian, Jinqin
Wu, Yucai
Zhu, Zhenpeng
Yu, Wei
Gong, Yanqing
Li, Xuesong
He, Zhisong
Zhou, Liqun
TI Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; WGCNA; signature; neuroendocrine prostate cancer (NEPC); LASSO; mCRPC
ID biomarker; WGCNA; signature; neuroendocrine prostate cancer (NEPC); LASSO; mCRPC
AB Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks wellcharacterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing antiandrogen receptor therapy or switching to platinum-based chemotherapy. Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset. Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively. Conclusion: The present study identified four specific novel biomarkers for therapyrelated NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.
C1 [Zhang, Cuijian] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Qian, Jinqin] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Wu, Yucai] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Zhu, Zhenpeng] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Yu, Wei] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Gong, Yanqing] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Li, Xuesong] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[He, Zhisong] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
[Zhou, Liqun] Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of UrologyBeijing, China.
RP Zhang, C (reprint author), Peking University, Peking University First Hospital Institute of Urology, National Urological Cancer Center, Department of Urology, Beijing, China.
EM surgeon_zhang@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609968
EP 1609980
DI 10.3389/pore.2021.1609968
PG 13
ER
PT J
TI Retraction: MiR-424-5p Inhibits Proliferation, Invasion and Promotes Apoptosis and Predicts Good Prognosis in Glioma by Directly Targeting BFAR
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB MiR-424-5p Inhibits Proliferation, Invasion and Promotes Apoptosis and Predicts Good Prognosis in Glioma by Directly Targeting BFAR by Cheng, Z., Shu, H., Cui, Y., Zhang, Q., Zhao, B., Pan, D., Chao, Q., and Wang, D. (2020). MiR-424- 5p Inhibits Proliferation, Invasion and Promotes Apoptosis and Predicts Good Prognosis in Glioma by Directly Targeting BFAR. Pathol. Oncol. Res. 26, 2327–2335. doi: 10.1007/s12253-020-00831-1
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2021
VL 27
IS 3
BP 1609970
EP 1609970
DI 10.3389/pore.2021.1609970
PG 1
ER
PT J
AU Chen, L
Chen, Y
Zhang, L
Xue, Y
Zhang, Sh
Li, X
Song, H
AF Chen, Li
Chen, Yong
Zhang, Lele
Xue, Yingwei
Zhang, Shiwei
Li, Xingrui
Song, Hongjiang
TI In Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy Systemic Inflammation Response Index is a Useful Prognostic Indicator
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; neoadjuvant chemotherapy; advanced gastric cancer; systemic inflammation response index (SIRI); tumor indicator
ID prognosis; neoadjuvant chemotherapy; advanced gastric cancer; systemic inflammation response index (SIRI); tumor indicator
AB Background: The preoperative systemic inflammation response index (SIRI), based on peripheral neutrophil (N), monocyte (M), and lymphocyte (L) counts, has shown mounting evidence as an effective prognostic indicator in some malignant tumors. The aim of the present study was to evaluate the prognostic significance of pretreatment SIRI in gastric cancer patients who received neoadjuvant chemotherapy (NACT). Methods: This retrospective study comprised 107 patients with advanced gastric cancer treated with NACT between July 2007 and September 2015 in our hospital. SIRI was calculated from peripheral venous blood samples obtained prior to treatment. The best cutoff value for SIRI by receiver operating characteristic (ROC) curve was 1.2 (low SIRI <1.21, high SIRI ≥1.21). The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis and compared using the logrank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model. Results: The results demonstrated that the low SIRI group was statistically associated with gender, primary tumor site, white blood cell, neutrophil, and monocyte counts, NLR (neutrophil to lymphocyte ratio), MLR (monocyte to lymphocyte ratio), and PLR (platelet to lymphocyte ratio). The SIRI was predictive for DFS and OS by univariate and multivariate analysis; the low SIRI group had better median DFS and OS than the high SIRI group (median DFS 27.03 vs. 22.33 months, median OS 29.73 vs. 24.43 months). The DFS and OS in the low SIRI group were longer than the high SIRI group. Conclusions: SIRI may qualify as a useful, reliable, and convenient prognostic indicator in patients with advanced gastric cancer to help physicians to provide personalized prognostication for gastric cancer patients treated with NACT.
C1 [Chen, Li] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thyroid and Breast SurgeryWuhan, China.
[Chen, Yong] Huai’an Second People’s Hospital and the Affiliated Huai’an Hospital of Xuzhou Medical University, Department of General SurgeryHuai’an, China.
[Zhang, Lele] Harbin Medical University, Harbin Medical University Cancer Hospital, Department of Gastrointestinal SurgeryHarbin, China.
[Xue, Yingwei] Harbin Medical University, Harbin Medical University Cancer Hospital, Department of Gastrointestinal SurgeryHarbin, China.
[Zhang, Shiwei] The First People’s Hospital of Fuyang Hangzhou, Department of Oncology SurgeryHangzhou, China.
[Li, Xingrui] Huazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Thyroid and Breast SurgeryWuhan, China.
[Song, Hongjiang] Harbin Medical University, Harbin Medical University Cancer Hospital, Department of Gastrointestinal SurgeryHarbin, China.
RP Song, H (reprint author), Harbin Medical University, Harbin Medical University Cancer Hospital, Department of Gastrointestinal Surgery, Harbin, China.
EM hongjiangsong2016@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609811
EP 1609820
DI 10.3389/pore.2021.1609811
PG 10
ER
PT J
AU Qadir, J
Majid, S
Khan, SM
Rashid, F
Wani, DM
Bhat, ASh
AF Qadir, Jasiya
Majid, Sabhiya
Khan, Saleem Mosin
Rashid, Fouzia
Wani, Din Mumtaz
Bhat, Ahmad Showkat
TI Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; ARID1A; mutation; mRNA expression 3; mRNA expression; qRT-PCR; TP53; PDL1
ID gastric cancer; ARID1A; mutation; mRNA expression 3; mRNA expression; qRT-PCR; TP53; PDL1
AB AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell deathligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. ThemRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reducedmRNA expression of ARID1A and elevatedmRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.
C1 [Qadir, Jasiya] Government Medical College Srinagar and Associated Hospitals, Department of BiochemistrySrinagar, India.
[Majid, Sabhiya] Government Medical College Srinagar and Associated Hospitals, Department of BiochemistrySrinagar, India.
[Khan, Saleem Mosin] Government Medical College Srinagar and Associated Hospitals, Department of BiochemistrySrinagar, India.
[Rashid, Fouzia] University of Kashmir, Department of Clinical BiochemistrySrinagar, India.
[Wani, Din Mumtaz] Government Medical College Srinagar and Associated Hospitals, Department of SurgerySrinagar, India.
[Bhat, Ahmad Showkat] Government Medical College, Department of BiochemistryDoda, India.
RP Majid, S (reprint author), Government Medical College Srinagar and Associated Hospitals, Department of Biochemistry, Srinagar, India.
EM sabuumajid@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609826
EP 1609838
DI 10.3389/pore.2021.1609826
PG 13
ER
PT J
AU Chen, Ch
Wang, T
Yang, M
Song, J
Huang, M
Bai, Y
Su, H
AF Chen, Chen
Wang, Tao
Yang, Mengmei
Song, Jia
Huang, Mengli
Bai, Yuezong
Su, Hao
TI Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Advanced Biliary Tract Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE next-generation sequencing; signaling pathway; circulating tumor DNA; biliary tract cancer; genomic feature
ID next-generation sequencing; signaling pathway; circulating tumor DNA; biliary tract cancer; genomic feature
AB Background: Biliary tract cancer is a highly lethal malignancy with poor clinical outcome. Accumulating evidence indicates targeted therapeutics may provide new hope for improving treatment response in BTC, hence better understanding the genomic profile is particularly important. Since tumor tissue may not be available for some patients, a complementary method is urgently needed. Circulating tumor DNA (ctDNA) provides a noninvasive means for detecting genomic alterations, and has been regarded as a promising tool to guide clinical therapies. Methods: Next-generation sequencing of 150 cancer-related genes was used to detect gene alterations in blood-derived ctDNA from 154 Chinese patients with BTC. Genomic alterations were analyzed and compared with an internal tissue genomic database and TCGA database. Results: 94.8% patients had at least one change detected in their ctDNA. The median maximumsomatic allele frequency was 6.47% (ranging 0.1–34.8%). TP53 and KRAS were the most often mutated genes. The frequencies of single nucleotide variation in commonly mutated genes in ctDNA were similar to those detected in tissue samples, TP53 (35.1 vs. 40.4%) and KRAS (20.1 vs. 22.6%). Pathway analysis revealed that mutated genes were mapped to several key pathways including PI3K-Akt, p53, ErbB and Ras signaling pathway. In addition, patients harboring LRP1B, TP53, and ErbB family mutations presented significantly higher tumor mutation burden. Conclusions: These findings demonstrated that ctDNA testing by NGS was feasible in revealing genomic changes and could be a viable alternative to tissue biopsy in patients with metastatic BTC.
C1 [Chen, Chen] Hunan Provincial People’s Hospital, Department of Hepatobiliary and Pancreatic SurgeryChangsha, China.
[Wang, Tao] Hunan Provincial People’s Hospital, Department of Hepatobiliary and Pancreatic SurgeryChangsha, China.
[Yang, Mengmei] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Song, Jia] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Huang, Mengli] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Bai, Yuezong] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Su, Hao] First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary SurgeryNanning, China.
RP Su, H (reprint author), First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China.
EM tntboy1982@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609879
EP 1609887
DI 10.3389/pore.2021.1609879
PG 9
ER
PT J
TI The Advance and Correlation of KRAS Mutation With the Fertility-Preservation Treatment of Endometrial Cancer in the Background of Molecular Classification Application
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE KRAS mutation; endometrial cancer; fertility-preservation; fertility-spared; conservative treatment; molecular classification
ID KRAS mutation; endometrial cancer; fertility-preservation; fertility-spared; conservative treatment; molecular classification
AB The annually increasing incidence of endometrial cancer in younger women has created a growing demand for fertility preservation. However, the diverse therapeutic efficacy among patients under the same histological subtype and the same tumor grade suggests the potential interference of the innate molecular characteristics. The molecular classification has now been applied in clinical practice and might help to stratify the endometrial cancer patients and individualize the therapy, but the candidates for the fertility-spared treatment are most likely to be subdivided in the subgroup lacking the specific signature. KRAS mutation has been linked to the malignant transition of the endometrium, while its role in molecular classification and fertility preservation is vague. Here, we mainly review the advance of molecular classification and the role of KRAS in endometrial cancer, as well as their correlation with fertility-preservation treatment.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609906
EP 1609911
DI 10.3389/pore.2021.1609906
PG 6
ER
PT J
AU Reedy, M
Jonnalagadda, Sh
Palle, K
AF Reedy, Mark
Jonnalagadda, Shirisha
Palle, Komaraiah
TI Case Report: Intra-Tumoral Vaccinations of Quadrivalent HPV-L1 Peptide Vaccine With Topical TLR-7 Agonist Following Recurrence: Complete Resolution of HPV-HR-Associated Gynecologic Squamous Cell Carcinomas in Two Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE human papilloma virus high-risk variant; radiation refractory squamous cell carcinoma; quadrivalent HPV-L1 vaccine; intratumoral injection; toll-like receptor 7 agonist; immunotherapy
ID human papilloma virus high-risk variant; radiation refractory squamous cell carcinoma; quadrivalent HPV-L1 vaccine; intratumoral injection; toll-like receptor 7 agonist; immunotherapy
AB The human papilloma virus (HPV) high-risk variants (HPV-HR) such as HPV16 and HPV18 are responsible for most HPV related cancers, including anogenital and head and neck cancers. Here, we present two patients with HPV-HR-associated gynecological malignancies who, after failing radiation therapy, were treated with experimental salvage immunotherapy regimen resulting in complete, durable responses in both patients. Each patient was diagnosed with recurrent, radiation-refractory, HPV-HR positive, squamous cell carcinoma of the lower genital tract. Patient A was a 90-yearold, African American, with metastatic vulvar cancer to the right inguinal-femoral triangle and pulmonary metastases. Patient B was a 41-year-old, Caucasian, with a centralrecurrence of cervix cancer. Each patient received at least two intratumoral quadrivalent HPV-L1 vaccine (Gardasil™) injections and daily topical TLR-7 agonist (imiquimod) to the tumor surface 2 weeks apart. This combination of intratumoral vaccinations and topical TLR-7 agonist produced unexpected complete resolution of disease in both patients. The importance of radiation therapy, despite being considered a treatment failure by current definitions, cannot be understated. Radiation therapy appears to have offered a therapeutic immune advantage by modifying the tumor microenvironment. This immune protocol has potential to help patients with advanced HPV-HR-related malignancies previously considered incurable.
C1 [Reedy, Mark] Texas Tech University Health Sciences Center, School of Medicine, Department of Obstetrics and GynecologyLubbock, TX, USA.
[Jonnalagadda, Shirisha] Texas Tech University Health Sciences Center, Department of Cell Biology and BiochemistryLubbock, TX, USA.
[Palle, Komaraiah] Texas Tech University Health Sciences Center, Department of Cell Biology and BiochemistryLubbock, TX, USA.
RP Reedy, M (reprint author), Texas Tech University Health Sciences Center, School of Medicine, Department of Obstetrics and Gynecology, Lubbock, USA.
EM Mark.Reedy@ttuhsc.edu
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Chuang C-M, Monie A, Hung C-F, Wu T-C. Treatment with Imiquimod Enhances Antitumor Immunity Induced by Therapeutic HPV DNA Vaccination. J Biomed Sci, 2010, 17:32., DOI 10.1186/1423-0127-17-32
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609922
EP 1609927
DI 10.3389/pore.2021.1609922
PG 6
ER
PT J
AU Yao, ZG
Wei, ZG
Cheng, XK
Huang, GH
Zong, YY
Meng, M
Li, JM
Han, XY
Xu, JW
Wang, J
Jing, HY
Li, WH
Cao, ZX
Ni, Y
Sun, XCh
Yang, X
Ye, X
AF Yao, Zhi-Gang
Wei, Zhi-Gang
Cheng, Xian-Kui
Huang, Guang-Hui
Zong, Yuan-Yuan
Meng, Min
Li, Jia-Mei
Han, Xiao-Ying
Xu, Jia-Wen
Wang, Jiao
Jing, Hai-Yan
Li, Wen-Hong
Cao, Zhi-Xin
Ni, Yang
Sun, Xi-Chao
Yang, Xia
Ye, Xin
TI Comparison of Multi-Gene Testing Data Between Fresh and Formalin-Fixed Specimens From Core Needle Biopsy in Patients With NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pathology; EGFR; lung cancers; frozen section examination; fresh frozen tissue
ID pathology; EGFR; lung cancers; frozen section examination; fresh frozen tissue
AB Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients. Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing. Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients. Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients.
C1 [Yao, Zhi-Gang] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Wei, Zhi-Gang] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Cheng, Xian-Kui] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Huang, Guang-Hui] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Zong, Yuan-Yuan] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Meng, Min] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Li, Jia-Mei] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Han, Xiao-Ying] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Xu, Jia-Wen] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Wang, Jiao] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Jing, Hai-Yan] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Li, Wen-Hong] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Cao, Zhi-Xin] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Ni, Yang] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Sun, Xi-Chao] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Yang, Xia] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Ye, Xin] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
RP Ye, X (reprint author), Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Oncology, Jinan, China.
EM yexintaian2020@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609931
EP 1609939
DI 10.3389/pore.2021.1609931
PG 9
ER
PT J
AU Cai, H
Chen, H
Huang, Q
Zhu, JM
Ke, ZB
Lin, YZ
Zheng, QSh
Wei, Y
Xu, N
Xue, XY
AF Cai, Hai
Chen, Hang
Huang, Qi
Zhu, Jun-Ming
Ke, Zhi-Bin
Lin, Yun-Zhi
Zheng, Qing-Shui
Wei, Yong
Xu, Ning
Xue, Xue-Yi
TI Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; bladder cancer; ubiquitination; molecular subtypes; prognostic index
ID prognosis; bladder cancer; ubiquitination; molecular subtypes; prognostic index
AB Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa). Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitinationrelated molecular subtypes and prognostic index with tumor immune environment were also investigated. Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients. Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.
C1 [Cai, Hai] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Chen, Hang] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Huang, Qi] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Zhu, Jun-Ming] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Ke, Zhi-Bin] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Lin, Yun-Zhi] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Zheng, Qing-Shui] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Wei, Yong] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Xu, Ning] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
[Xue, Xue-Yi] The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of UrologyFuzhou, China.
RP Xue, XY (reprint author), The First Affiliated Hospital, Fujian Medical University, Urology Research Institute, Department of Urology, Fuzhou, China.
EM xuexueyi@fjmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609941
EP 1609957
DI 10.3389/pore.2021.1609941
PG 17
ER
PT J
AU Jiang, Y
Gu, H
Zheng, X
Pan, B
Liu, P
Zheng, M
AF Jiang, Yinan
Gu, Haifeng
Zheng, Xiaojing
Pan, Baoyue
Liu, Pingping
Zheng, Min
TI Pretreatment C-Reactive Protein/ Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE recurrence; survival; CAR; prognostic markers; UCC; HPV
ID recurrence; survival; CAR; prognostic markers; UCC; HPV
AB Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients. Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yatsen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients. Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis. Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.
C1 [Jiang, Yinan] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Gu, Haifeng] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Zheng, Xiaojing] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Pan, Baoyue] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Liu, Pingping] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Zheng, Min] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
RP Zheng, M (reprint author), Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecology, Guangzhou, China.
EM zhengmin@sysucc.org.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609946
EP 1609959
DI 10.3389/pore.2021.1609946
PG 14
ER
PT J
AU Govoni, M
Rossi, V
Stefano, DG
Manerba, M
AF Govoni, Marzia
Rossi, Valentina
Stefano, Di Giuseppina
Manerba, Marcella
TI Lactate Upregulates the Expression of DNA Repair Genes, Causing Intrinsic Resistance of Cancer Cells to Cisplatin
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE DNA repair; cisplatin; glycolysis; lactate; DNA damage
ID DNA repair; cisplatin; glycolysis; lactate; DNA damage
AB Intrinsic or acquired drug resistance is one of the major problems compromising the success of antineoplastic treatments. Several evidences correlated some therapeutic failures with changes in cell metabolic asset and in line with these findings, hindering the glycolytic metabolism of cancer cells via lactate dehydrogenase (LDH) inhibition was found to overcome the resistance to chemotherapeutic agents. Lactate, the product of LDH reaction, was shown to be involved in epigenetic regulation of gene expression. The experiments described in this paper were aimed at highlighting a possible direct effect of lactate in modifying the response of cancer cells to a chemotherapeutic treatment. To discriminate between the effects potentially caused by glycolytic metabolism from those directly referable to lactate, we selected cancer cell lines able to grow in glucose deprived conditions and evaluated the impact of lactate on the cellular response to cisplatin-induced DNA damage. In lactate-exposed cells we observed a reduced efficacy of cisplatin, which was associated with reduced signatures of DNA damage, enhanced DNA recombination competence and increased expression of a panel of genes involved in DNA repair. The identified genes take part in mismatch and nucleotide excision repair pathways, which were found to contribute in restoring the cisplatin-induced DNA damage. The obtained results suggest that this metabolite could play a role in reducing the efficacy of antineoplastic treatments.
C1 [Govoni, Marzia] University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES)Bologna, Italy.
[Rossi, Valentina] University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES)Bologna, Italy.
[Stefano, Di Giuseppina] University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES)Bologna, Italy.
[Manerba, Marcella] University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES)Bologna, Italy.
RP Stefano, DG (reprint author), University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna, Italy.
EM giuseppina.distefano@unibo.it
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609951
EP 1609959
DI 10.3389/pore.2021.1609951
PG 9
ER
PT J
AU Zhao, X
Wu, Sh
Jing, J
AF Zhao, Xu
Wu, Shuang
Jing, Jingjing
TI Identifying Diagnostic and Prognostic Biomarkers and Candidate Therapeutic Drugs of Gastric Cancer Based on Transcriptomics and Single-Cell Sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bioinformatics; biomarkers; prognosis; gastric cancer; hub genes; molecular drugs
ID bioinformatics; biomarkers; prognosis; gastric cancer; hub genes; molecular drugs
AB Background and Objective: Gastric cancer (GC) is an important health burden and the prognosis of GC is poor. We aimed to explore new diagnostic and prognostic indicators as well as potential therapeutic targets for GC in the current study. Methods: We screened the overlapped differentially expressed genes (DEGs) from GSE54129 and TCGA STAD datasets. Protein-protein interaction network analysis recognized the hub genes among the DEGs. The roles of these genes in diagnosis, prognosis, and their relationship with immune infiltrates and drug sensitivity of GC were analyzed using R studio. Finally, the clinically significant hub genes were verified using single-cell RNA sequencing (scRNA-seq) data. Results: A total of 222 overlapping genes were screened, which were enriched in extracellular matrix-related pathways. Further, 17 hub genes were identified, and our findings demonstrated that BGN, COMP, COL5A2, and SPARC might be important diagnostic and prognostic indicators of GC, which were also correlated with immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and sensitivity of therapeutic drugs. The scRNAseq results further confirmed that all four hub genes were highly expressed in GC. Conclusion: Based on transcriptomics and single-cell sequencing, we identified four diagnostic and prognostic biomarkers of GC, including BGN, COMP, COL5A2, and SPARC, which can help predict drug sensitivity for GC as well.
C1 [Zhao, Xu] Liaoning Vocational College of Medicine, Mathematical Computer Teaching and Research OfficeShenyang, China.
[Wu, Shuang] Changchun Normal University, College of Computer Science and TechnologyChangchun, China.
[Jing, Jingjing] China Medical University, The First Affiliated Hospital, Department of General SurgeryShenyang, China.
RP Jing, J (reprint author), China Medical University, The First Affiliated Hospital, Department of General Surgery, Shenyang, China.
EM hellojjjing@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609955
EP 1609968
DI 10.3389/pore.2021.1609955
PG 14
ER
PT J
AU Yang, ML
Zhang, JH
Li, Sh
Zhu, R
Wang, L
AF Yang, Meng-Ling
Zhang, Jia-Hua
Li, Sheng
Zhu, Rui
Wang, Li
TI SLC13A4 Might Serve as a Prognostic Biomarker and be Correlated with Immune Infiltration into Head and Neck Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; tumor-infiltrating immune cells; SLC13A4; head and neck squamous cell carcinoma; database analysis
ID biomarker; tumor-infiltrating immune cells; SLC13A4; head and neck squamous cell carcinoma; database analysis
AB SLC13A4 is a sodium sulfate co-transporter, which is expressed in brains, placentas, thymes and other tissues, plays an essential role in maintaining the metabolic balance of sulfate in vivo. The TCGA database shows that it is differentially expressed in a variety of tumors, but its prognostic value in tumors has not been clarified. TCGA, Oncomine and Timer databases were used to analyze SLC13A4 mRNA expression in cancer tissues and normal tissues, and its correlation with clinical prognosis in head and neck tumor. The CIBERSORT database was used to analyze the correlation between SLC13A4 expression and the infiltration of immune cells. SLC13A4 enrichment analysis was carried out by GSEA. SLC13A4 mRNA levels were significantly lower in head and neck tumors than in paracancer tissues. SLC13A4 expression in Head and neck squamous cell carcinoma (HNSCC) was closely related to tumor pathological grade and clinical stage. Decreased SLC13A4 expression was associated with poor overall survival (OS), progression free survival (PFS), disease specific survival (DSS) and recurrence free survival (RFS) in HNSCC patients. The expression of SLC13A4 was negatively correlated with Monocytes, M1 macrophages, M2 macrophages, resting CD4+ memory T cells, resting NK cells and activated NK cells, but positively correlated with neutrophils, plasma cells, T follicular helper cells, gamma delta T cells, regulatory T cells and naive B cells. In addition, the genes in SLC13A4 low-expression group were mainly concentrated in immunity-related activities, viral diseases, typical tumor pathways and metabolism. The SLC13A4 high expression group was mainly enriched in metabolic pathways. These suggest that SLC13A4 may be a potential prognostic biomarker in HNSC and correlated with immune infiltrates.
C1 [Yang, Meng-Ling] Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Department of Integrated Traditional Chinese and Western MedicineWuhan, China.
[Zhang, Jia-Hua] Huazhong University of Science and Technology, Tongji Medical College, Center of Stem cellWuhan, China.
[Li, Sheng] Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Department of SurgeryWuhan, China.
[Zhu, Rui] Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Department of Integrated Traditional Chinese and Western MedicineWuhan, China.
[Wang, Li] Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Department of Emergency SurgeryWuhan, China.
RP Zhu, R (reprint author), Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Department of Integrated Traditional Chinese and Western Medicine, Wuhan, China.
EM zhur@hust.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609967
EP 1609981
DI 10.3389/pore.2021.1609967
PG 15
ER
PT J
AU Brunner, Sz
Varga, D
Bozo, R
Polanek, R
Tokes, T
Szabo, RE
Molnar, R
Gemes, N
Szebeni, G
Puskas, L
Erdelyi, M
Hideghety, K
AF Brunner, Szilvia
Varga, Daniel
Bozo, Renata
Polanek, Robert
Tokes, Tunde
Szabo, Rita Emilia
Molnar, Reka
Gemes, Nikolett
Szebeni, J. Gabor
Puskas, G. Laszlo
Erdelyi, Miklos
Hideghety, Katalin
TI Analysis of Ionizing Radiation Induced DNA Damage by Superresolution dSTORM Microscopy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ionizing radiation; γ-H2AX; DNA-DSB; confocal microscopy; dSTORM; superresolution
ID ionizing radiation; γ-H2AX; DNA-DSB; confocal microscopy; dSTORM; superresolution
AB The quantitative detection of radiation caused DNA double-strand breaks (DSB) by immunostained γ-H2AX foci using direct stochastic optical reconstruction microscopy (dSTORM) provides a deeper insight into the DNA repair process at nanoscale in a timedependent manner. Glioblastoma (U251) cells were irradiated with 250 keV X-ray at 0, 2, 5, 8 Gy dose levels. Cell cycle phase distribution and apoptosis of U251 cells upon irradiation was assayed by flow cytometry. We studied the density, topology and volume of the γ-H2AX foci with 3D confocal microscopy and the dSTORM superresolution method. A pronounced increase in γ-H2AX foci and cluster density was detected by 3D confocal microscopy after 2 Gy, at 30 min postirradiation, but both returned to the control level at 24 h. Meanwhile, at 24 h a considerable amount of residual foci could be measured from 5 Gy, which returned to the normal level 48 h later. The dSTORM based γ-H2AX analysis revealed that the micron-sized γ-H2AX foci are composed of distinct smaller units with a few tens of nanometers. The density of these clusters, the epitope number and the dynamics of γ-H2AX foci loss could be analyzed. Our findings suggest a discrete level of repair enzyme capacity and the restart of the repair process for the residual DSBs, even beyond 24 h. The dSTORM superresolution technique provides a higher precision over 3D confocal microscopy to study radiation induced γ-H2AX foci and molecular rearrangements during the repair process, opening a novel perspective for radiation research.
C1 [Brunner, Szilvia] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
[Varga, Daniel] University of Szeged, Department of Optics and Quantum ElectronicsSzeged, Hungary.
[Bozo, Renata] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Polanek, Robert] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
[Tokes, Tunde] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
[Szabo, Rita Emilia] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
[Molnar, Reka] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
[Gemes, Nikolett] Szegedi Biologiai Kutatokozpont, Funkcionalis Genomika LaboratoriumSzeged, Hungary.
[Szebeni, J. Gabor] Szegedi Biologiai Kutatokozpont, Funkcionalis Genomika LaboratoriumSzeged, Hungary.
[Puskas, G. Laszlo] Szegedi Biologiai Kutatokozpont, Funkcionalis Genomika LaboratoriumSzeged, Hungary.
[Erdelyi, Miklos] University of Szeged, Department of Optics and Quantum ElectronicsSzeged, Hungary.
[Hideghety, Katalin] ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications GroupSzeged, Hungary.
RP Hideghety, K (reprint author), ELI-HU Non-Profit Ltd, ELI-ALPS Research Institute, Biomedical Applications Group, Szeged, Hungary.
EM katalin.hideghety@eli-alps.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609971
EP 1609983
DI 10.3389/pore.2021.1609971
PG 13
ER
PT J
AU Tan, Sh
Fu, X
Xu, Sh
Qiu, P
Lv, Z
Xu, Y
Zhang, Q
AF Tan, Shirong
Fu, Xin
Xu, Shouping
Qiu, Pengfei
Lv, Zhidong
Xu, Yingying
Zhang, Qiang
TI Quantification of Ki67 Change as a Valid Prognostic Indicator of Luminal B Type Breast Cancer After Neoadjuvant Therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; prognosis; neoadjuvant chemotherapy; Ki67; tumor response
ID breast cancer; prognosis; neoadjuvant chemotherapy; Ki67; tumor response
AB Introduction: Ki67 value and its variation before and after neoadjuvant chemotherapy are commonly tested in relation to breast cancer patient prognosis. This study aims to quantify the extent of changes in Ki67 proliferation pre- and post-neoadjuvant chemotherapy, confirm an optimal cut-off point, and evaluate its potential value for predicting survival outcomes in patients with different molecular subtypes of breast cancer. Methods: This retrospective real-world study recruited 828 patients at the Department of Breast Surgery of the First Affiliated Hospital of China Medical University and the Cancer Hospital of China Medical University from Jan 2014 to Nov 2020. Patient demographic features and disease pathology characteristics were recorded, and biomarkers were verified through immunohistochemistry. Various statistical methods were used to validate the relationships between different characteristics and survival outcomes irrespective of disease-free and overall survival. Results: Among 828 patients, statistically significant effects between pathological complete response and survival outcome were found in both HER2-enriched and triple-negative breast cancer (p < 0.05) but not in Luminal breast cancer (p > 0.05). Evident decrease of Ki67 was confirmed after neoadjuvant chemotherapy. To quantify the extent of Ki67 changes between pre- and post-NAC timepoints, we adopted a computational equation termed ΔKi67% for research. We found the optimal cut-off value to be “ΔKi67% = −63%” via the operating characteristic curve, defining ΔKi67% ≤ −63% as positive status and ΔKi67% > −63% as negative status. Patients with positive ΔKi67% status were 37.1% of the entire cohort. Additionally, 4.7, 39.9, 34.5 and 39.6% of patients with Luminal A, Luminal B, HER2-enriched and triple negative breast cancer were also validated with positive ΔKi67% status. The statistically significant differences between ΔKi67% status and prognostic outcomes were confirmed by univariate and multivariate analysis in Luminal B (univariate and multivariate analysis: p < 0.05) and triple negative breast cancer (univariate and multivariate analysis: p < 0.05). We proved ΔKi67% as a statistically significant independent prognostic factor irrespective of disease-free or overall survival among patients with Luminal B and triple-negative breast cancer. Conclusions: ΔKi67% can aid in predicting patient prognostic outcome, provide a measurement of NAC efficacy, and assist in further clinical decisions, especially for patients with Luminal B breast cancer.
C1 [Tan, Shirong] The First Affiliated Hospital of China Medical University, Department of Breast SurgeryShenyang, China.
[Fu, Xin] Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Department of Breast SurgeryShenyang, China.
[Xu, Shouping] Harbin Medical University Cancer Hospital, Department of Breast SurgeryHarbin, China.
[Qiu, Pengfei] Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Breast Cancer CenterJinan, China.
[Lv, Zhidong] The Affiliated Hospital of Qingdao University, Breast CenterQingdao, China.
[Xu, Yingying] The First Affiliated Hospital of China Medical University, Department of Breast SurgeryShenyang, China.
[Zhang, Qiang] Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Department of Breast SurgeryShenyang, China.
RP Zhang, Q (reprint author), Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Department of Breast Surgery, Shenyang, China.
EM zhangqiang8220@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609972
EP 1609987
DI 10.3389/pore.2021.1609972
PG 16
ER
PT J
AU Guo, Y
Liu, Y
Yang, H
Dai, N
Zhou, F
Yang, H
Sun, W
Kong, J
Yuan, X
Gao, Sh
AF Guo, Yibo
Liu, Yiwen
Yang, Haijun
Dai, Ningtao
Zhou, Fuyou
Yang, Hong
Sun, Wei
Kong, Jinyu
Yuan, Xiang
Gao, Shegan
TI Associations of Porphyromonas gingivalis Infection and Low Beclin1 Expression With Clinicopathological Parameters and Survival of Esophageal Squamous Cell Carcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE P.gingivalis; ESCC; Autophagy; Beclin1; Prognosis
ID P.gingivalis; ESCC; Autophagy; Beclin1; Prognosis
AB Purpose: The present study focused on exploring the associations of Porphyromonas gingivalis (P. gingivalis) infection and low Beclin1 expression with clinicopathological parameters and survival of esophageal squamous cell carcinoma (ESCC) patients, so as to illustrate its clinical significance and prognostic value. Methods: Immunohistochemistry (IHC) was used to detect P. gingivalis infection status and Beclin1 expression in 370 ESCC patients. The chi-square test was adopted to illustrate the relationship between categorical variables, and Cohen’s kappa coefficient was used for correlation analysis. Kaplan-Meier survival curves with the log-rank test were used to analyse the correlation of P. gingivalis infection and low Beclin1 expression with survival time. The effects of P. gingivalis infection and Beclin1 downregulation on the proliferation, migration and antiapoptotic abilities of ESCC cells in vitro were detected by Cell Counting Kit-8, wound healing and flow cytometry assays. For P. gingivalis infection of ESCC cells, cell culture medium was replaced with antibiotic-free medium when the density of ESCC cells was 70–80%, cells were inoculated with P. gingivalis at a multiplicity of infection (MOI) of 10. Result: P. gingivalis infection was negatively correlated with Beclin1 expression in ESCC tissues, and P. gingivalis infection and low Beclin1 expression were associated with differentiation status, tumor invasion depth, lymph node metastasis, clinical stage and prognosis in ESCC patients. In vitro experiments confirmed that P. gingivalis infection and Beclin1 downregulation potentiate the proliferation, migration and antiapoptotic abilities of ESCC cells (KYSE150 and KYSE30). Our results provide evidence that P. gingivalis infection and low Beclin1 expression were associated with the development and progression of ESCC. Conclusion: Long-term smoking and alcohol consumption causes poor oral and esophageal microenvironments and ESCC patients with these features were more susceptible to P. gingivalis infection and persistent colonization, and exhibited lower Beclin1 expression, worse prognosis and more advanced clinicopathological features. Our findings indicate that effectively eliminating P. gingivalis colonization and restoring Beclin1 expression in ESCC patients may contribute to preventation and targeted treatment, and yield new insights into the aetiological research on ESCC.
C1 [Guo, Yibo] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Liu, Yiwen] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Yang, Haijun] Anyang Tumor Hospital, Department of Thoracic SurgeryAnyang, China.
[Dai, Ningtao] Anyang Tumor Hospital, Department of Thoracic SurgeryAnyang, China.
[Zhou, Fuyou] Anyang Tumor Hospital, Department of Thoracic SurgeryAnyang, China.
[Yang, Hong] Henan University of Science and Technology, School of PELuoyang, China.
[Sun, Wei] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Kong, Jinyu] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Yuan, Xiang] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
[Gao, Shegan] Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer InstituteLuoyang, China.
RP Gao, Sh (reprint author), Henan University of Science and Technology, College of Clinical Medicine, The First Affiliated Hospital, Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, Luoyang, China.
EM gsg112258@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609976
EP 1609987
DI 10.3389/pore.2021.1609976
PG 12
ER
PT J
AU Zheng, H
Ning, Y
Yang, Y
Zhan, Y
Wang, H
Wen, Q
Peng, J
Fan, S
AF Zheng, Hongmei
Ning, Yue
Yang, Yang
Zhan, Yuting
Wang, Haihua
Wen, Qiuyuan
Peng, Jinwu
Fan, Songqing
TI Aberrant Expression of β-Catenin Correlates with Infiltrating Immune Cells and Prognosis in NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; NSCLC; β-catenin; tumor microenvironment; tumor immunity
ID biomarker; NSCLC; β-catenin; tumor microenvironment; tumor immunity
AB Aims: β-catenin is a critical regulating factor of the Wnt pathway, which is closely linked to tumorigenesis, tumor growth, metastasis, and tumor immunity. Our study focused on exploring the relationship between β-catenin and clinicopathological features, prognosis, as well as infiltrating immune cells and immune scores, so as to illustrate its clinical significance in NSCLC. Materials and Methods: The β-catenin mRNA (CTNNB1) and protein expression data were downloaded from the UALCAN and the UCSC Xena website, respectively. All tumorimmune infiltrating cells’ data were downloaded from the TIMER platform and immune scores were downloaded from ESTIMATE website. The expression of β-catenin protein in our cohort was measured by immunohistochemistry. Results: β-catenin mRNA level was higher in lung adenocarcinoma (LUAD) compared to normal tissues (p < 0.001) and was related to overall survival (OS) (p < 0.001) and postprogression survival (PPS) (both p = 0.049) in LUAD. Aberrant β-catenin protein expression was higher in male and lung squamous cell carcinoma (LUSC) patients (both p = 0.001). Also, it was considered to be a prognosis factor independently (p = 0.034). In addition, β-catenin protein was negatively correlated with CD8+T cells (r = −0.128, p = 0.008), neutrophils (r = −0.198, p < 0.001), immune score (r = −0.109, p = 0.024), stromal score (r = −0.097, p = 0.045), and ESTIMATE score (r = −0.113, p = 0.020). Conclusions: Aberrant β-catenin protein expression was evidently higher in NSCLC and might serve as a biomarker for poor prognosis. Most importantly, β-catenin protein might play an important part in tumor immunity and the tumor microenvironment by inhibiting the infiltration of CD8+ T cells and neutrophils.
C1 [Zheng, Hongmei] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Ning, Yue] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Yang, Yang] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Zhan, Yuting] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Wang, Haihua] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Wen, Qiuyuan] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
[Peng, Jinwu] Central South University, Xiangya Basic Medical College, Department of PathologyChangsha, China.
[Fan, Songqing] Central South University, Second Xiangya Hospital, Department of PathologyChangsha, China.
RP Fan, S (reprint author), Central South University, Second Xiangya Hospital, Department of Pathology, Changsha, China.
EM songqingfan@csu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609981
EP 1609989
DI 10.3389/pore.2021.1609981
PG 9
ER
PT J
AU Jiang, X
Zhang, W
Li, L
Xie, Sh
AF Jiang, Xili
Zhang, Wei
Li, Lifeng
Xie, Shucai
TI Integrated Transcriptomic Analysis Revealed Hub Genes and Pathways Involved in Sorafenib Resistance in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hepatocellular carcinoma; hub gene; sorafenib resistance; integrated bioinformatics analysis; transcriptomic analysis
ID hepatocellular carcinoma; hub gene; sorafenib resistance; integrated bioinformatics analysis; transcriptomic analysis
AB Hepatocellular carcinoma (HCC), a high mortality malignancy, has become a worldwide public health concern. Acquired resistance to the multikinase inhibitor sorafenib challenges its clinical efficacy and the survival benefits it provides to patients with advanced HCC. This study aimed to identify critical genes and pathways associated with sorafenib resistance in HCC using integrated bioinformatics analysis. Differentially expressed genes (DEGs) were identified using four HCC gene expression profiles (including 34 sorafenib-resistant and 29 sorafenib-sensitive samples) based on the robust rank aggregation method and R software. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and small molecules reversing sorafenib resistance were searched for using the connectivity map (CMAP) database. Pearson correlation and survival analyses of hub genes were performed using cBioPortal and Gene Expression Profiling and Interactive Analysis (GEPIA). Finally, the expression levels of hub genes in sorafenib-resistant HCC cells were verified using quantitative polymerase chain reaction (q-PCR). A total of 165 integrated DEGs (66 upregulated and 99 downregulated in sorafenib resistant samples compared sorafenib sensitive ones) primarily enriched in negative regulation of endopeptidase activity, extracellular exosome, and protease binding were identified. Some pathways were commonly shared between the integrated DEGs. Seven promising therapeutic agents and 13 hub genes were identified. These findings provide a strategy and theoretical basis for overcoming sorafenib resistance in HCC patients.
C1 [Jiang, Xili] The Second People’s Hospital of Hunan Province/Brain Hospital of Hunan Province, Department of RadiologyChangsha, China.
[Zhang, Wei] The Second People’s Hospital of Hunan Province/Brain Hospital of Hunan Province, Department of RadiologyChangsha, China.
[Li, Lifeng] Changsha Central Hospital, Department of RadiologyChangsha, China.
[Xie, Shucai] Central South University, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Department of Critical Care MedicineChangsha, China.
RP Xie, Sh (reprint author), Central South University, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Department of Critical Care Medicine, Changsha, China.
EM 282791444@qq.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609985
EP 1609999
DI 10.3389/pore.2021.1609985
PG 15
ER
PT J
AU Remenyi, Gy
Bereczky, Zs
Gindele, R
Ujfalusi, A
Illes,
Udvardy, M
AF Remenyi, Gyula
Bereczky, Zsuzsanna
Gindele, Reka
Ujfalusi, Aniko
Illes, Arpad
Udvardy, Miklos
TI rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE single nucleotide polymorphism; secondary erythrocytosis; von Hippel-Lindau gene; rs779805 polymorphism; phlebotomy
ID single nucleotide polymorphism; secondary erythrocytosis; von Hippel-Lindau gene; rs779805 polymorphism; phlebotomy
AB Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G>A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.
C1 [Remenyi, Gyula] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Bereczky, Zsuzsanna] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Gindele, Reka] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Ujfalusi, Aniko] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Remenyi, Gy (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM gremenyi@med.unideb.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609987
EP 1609992
DI 10.3389/pore.2021.1609987
PG 6
ER
PT J
AU Youssef, H
Radi, D
Abd El-Azeem, M
AF Youssef, M. K. Heba
Radi, A. Dina
Abd El-Azeem, A. Marwa
TI Expression of TSP50, SERCA2 and IL-8 in Colorectal Adenoma and Carcinoma: Correlation to Clinicopathological Factors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE clinicopathological factors; colorectal adenoma; colorectal carcinoma; immunohistochemistry; IL-8; SERCA2 TSP50
ID clinicopathological factors; colorectal adenoma; colorectal carcinoma; immunohistochemistry; IL-8; SERCA2 TSP50
AB Background: Colorectal cancer (CRC) is the third most common type of cancer, it is considered a genetically heterogeneous disease with different molecular pathways being involved in its initiation and progression. Testes-specific protease 50 (TSP50) gene is a member of cancer/testis antigens that encodes for threonine protease enzyme. Overexpression of TSP50 was found to enhance the progression and invasion of breast cancer and other malignant tumors. SERCA2 is widely expressed in several body tissues; its aberrant expression has been involved in many cancers. IL-8 is an inflammatory cytokine. Alongside its role in inflammation, its expression was reported to induce the migration of tumor cells. Aim: Study the expression of TSP50, SERCA2 and IL-8 in colorectal adenoma (CRA), CRC and normal colonic tissues to compare the expression of these biomarkers in relation to clinicopathological parameters and prognostic factors. Results: TSP50, SERCA2 and IL-8 expression varied between normal colonic tissues, CRA and CRC. Significant statistical association was detected between the three biomarkers’ overexpression and degree of dysplasia in CRA. Also, significant statistical relation was found between the three biomarkers’ overexpression and presence of lympho-vascular invasion, advanced TNM staging and high intra-tumoral inflammatory infiltrate. Multivariable analysis showed that the overexpression of the three biomarkers is significantly associated with worse prognosis. Conclusion: The expression of TSP50, SERCA2 and IL-8 was different between the normal tissue and neoplastic colorectal tissue on one hand and between CRA and CRC on the other. Increased expression of these biomarkers in neoplastic epithelial cells of colorectal carcinoma is associated with adverse prognostic factors and could be considered as independent prognostic factors.
C1 [Youssef, M. K. Heba] Tanta University, Faculty of Medicine, Department of PathologyTanta, Egypt.
[Radi, A. Dina] Tanta University, Faculty of Medicine, Department of PathologyTanta, Egypt.
[Abd El-Azeem, A. Marwa] Tanta University, Faculty of Medicine, Department of PathologyTanta, Egypt.
RP Abd El-Azeem, M (reprint author), Tanta University, Faculty of Medicine, Department of Pathology, Tanta, Egypt.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609990
EP 1610001
DI 10.3389/pore.2021.1609990
PG 12
ER
PT J
AU Csurgay, K
Zalatnai, A
Benczik, M
Csomo, KB
Horvath, F
Lorincz,
Komlos, Gy
Nemeth, Zs
AF Csurgay, Katalin
Zalatnai, Attila
Benczik, Marta
Csomo, Krisztian Benedek
Horvath, Ferenc
Lorincz, Adam
Komlos, Gyorgy
Nemeth, Zsolt
TI A Study of Prognostic Factors in Young Patients With Non-HPV Oral Cancer in Central Europe
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; young adult; risk factors; oral cancer; p16
ID immunohistochemistry; young adult; risk factors; oral cancer; p16
AB The etiological factors of squamous cell carcinomas of the head and neck have been well known for a long time. It is also well known that the incidence of oral cancer diagnosed in younger patients is on the rise. Due to the young age of these patients, the increase in the number of these cases and the fact that many of them neither smoke nor drink alcohol it has been suggested that other factors might be at play in the carcinogenesis of oral cancer. Thus, along the classic etiological factors of smoking and alcohol abuse certain molecular marker anomalies and the human papilloma virus (HPV) have emerged as potential factors. The aim of the present study is to verify the potential prognostic factors and to map the differences in biomarker expression between the young and the old patient groups. In the present study the immunohistochemical profile of samples obtained from oral squamous cell carcinomas was studied and compared with various clinico-pathological parameters. In 88 samples the expressions of p16, p53, Ki67, EGFR were studied with a tissue microarray technique under standard reaction conditions as well as the detection and typing of HPV infection with the Full Spectrum HPV DNA method. The biomarker expression profile of young patients with oral squamous cell carcinoma was compared to that of older patients (above 50). A significant difference was found between the immunohistochemical profile of the young and old patient groups in p16, Ki67 expression. The overall survival and progression free survival were influenced by p16 expression in young age.
C1 [Csurgay, Katalin] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Benczik, Marta] GenoID Molecular Diagnostic Laboratory, SYNLAB Hungary Ltd.Budapest, Hungary.
[Csomo, Krisztian Benedek] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Horvath, Ferenc] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Lorincz, Adam] King’s College, Department of Oral SurgeryLondon, UK.
[Komlos, Gyorgy] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
[Nemeth, Zsolt] Semmelweis University, Department of Oral and Maxillofacial SurgeryBudapest, Hungary.
RP Nemeth, Zs (reprint author), Semmelweis University, Department of Oral and Maxillofacial Surgery, Budapest, Hungary.
EM nemeth.zsolt@dent.semmelweisuniv.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609991
EP 1610001
DI 10.3389/pore.2021.1609991
PG 11
ER
PT J
AU Tang, J
Li, Y
Liu, B
Liang, W
Hu, S
Shi, M
Zeng, J
Li, M
Huang, M
AF Tang, Jiefu
Li, Yaling
Liu, Boxuan
Liang, Wei
Hu, Sanbao
Shi, Meilian
Zeng, Jie
Li, Mingzhen
Huang, Minjiang
TI Uncovering a Key Role of ETS1 on Vascular Abnormality in Glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glioblastoma; ETS1; endothelial; tumor vessel; vascular abnormality
ID glioblastoma; ETS1; endothelial; tumor vessel; vascular abnormality
AB Glioblastoma (GBM) is the most aggressive type of brain tumor. Microvascular proliferation and abnormal vasculature are the hallmarks of the GBM, aggravating disease progression and increasing patient morbidity. Here, we uncovered a key role of ETS1 on vascular abnormality in glioblastoma. ETS1 was upregulated in endothelial cells from human tumors compared to endothelial cells from paired control brain tissue. Knockdown of Ets1 in mouse brain endothelial cells inhibited cell migration and proliferation, and suppressed expression of genes associated with vascular abnormality in GBM. ETS1 upregulation in tumor ECs was dependent on TGFβ signaling, and targeting TGFβ signaling by inhibitor decreased tumor angiogenesis and vascular abnormality in CT-2A glioma model. Our results identified ETS1 as a key factor regulating tumor angiogenesis, and suggested that TGFβ inhibition may suppress the vascular abnormality driven by ETS1.
C1 [Tang, Jiefu] The First Affiliated Hospital of Hunan University of Medicine, Trauma CenterHuaihua, China.
[Li, Yaling] Xi’an People’s Hospital (Xi’an Fourth Hospital), Department of Obstetrics and GynaecologyXi’an, China.
[Liu, Boxuan] The Second People’s Hospital of Huaihua, Precision Medicine CenterHuaihua, China.
[Liang, Wei] The Second People’s Hospital of Huaihua, Department of OrthopaedicsHuaihua, China.
[Hu, Sanbao] Capital Medical University, Beijing Anzhen Hospital, Department of OrthopaedicsBeijing, China.
[Shi, Meilian] The Second People’s Hospital of Huaihua, Department of Infectious DiseasesHuaihua, China.
[Zeng, Jie] The Second People’s Hospital of Huaihua, Department of OrthopaedicsHuaihua, China.
[Li, Mingzhen] The Second People’s Hospital of Huaihua, Precision Medicine CenterHuaihua, China.
[Huang, Minjiang] Hunan University of MedicineHuaihua, China.
RP Huang, M (reprint author), Hunan University of Medicine, Huaihua, China.
EM zhenduan2010@126.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1609997
EP 1610006
DI 10.3389/pore.2021.1609997
PG 10
ER
PT J
AU Mell, L
Herrera, F
AF Mell, K. Loren
Herrera, G. Fernanda
TI SMARCA4-Deficient Carcinoma of Uterine Cervix Resembling SCCOHT—Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE cervical cancer; diagnostic biomarker; predictive marker; gynecological cancer; high-risk; personalized treatment; case report
ID cervical cancer; diagnostic biomarker; predictive marker; gynecological cancer; high-risk; personalized treatment; case report
AB Small cell carcinoma of hypercalcemic type (SCCOHT) is a rare gynaecological neoplasm, originating mostly in the ovaries. Cervical origin of this very aggressive malignancy with unknown histogenesis is an extremely rare condition, without published management recommendations. Alterations in SMARCA4 gene are supposed to play the major role in SCCOHT oncogenesis and their identification is crucial for the diagnosis. Adequate genetic counselling of the patients and their families seems to be of great importance. Optimal management and treatment approaches are not known yet but may extremely influence the prognosis of young female patients that suffer from this very resistant disease. Nowadays, a translational research seems to be the key for the further diagnostic and treatment strategies of SCCOHT. The purpose of the case report is to provide practical information and useful recommendations on the diagnosis, management, and treatment of SMARCA4-deficient carcinoma of the uterine cervix resembling SCCOHT.
C1 [Mell, K. Loren] University of California, Department of Radiation Medicine and Applied Sciences, La JollaSan Diego, CA, USA.
[Herrera, G. Fernanda] University of Lausanne, Lausanne University Hospital, Ludwig Institute for Cancer ResearchLausanne, Switzerland.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610003
EP 1610011
DI 10.3389/pore.2021.1610003
PG 9
ER
PT J
AU Bai, R
Diao, B
Li, K
Xu, X
Yang, P
AF Bai, Rui
Diao, Bowen
Li, Kaili
Xu, Xiaohan
Yang, Ping
TI Serum Tie-1 is a Valuable Marker for Predicting the Progression and Prognosis of Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; cervical cancer; diagnostic biomarker; Tie-1; angiopoietin
ID survival; cervical cancer; diagnostic biomarker; Tie-1; angiopoietin
AB Objective: To investigate whether serum Tie-1 (sTie-1) is a valuable marker for predicting progression and prognosis of cervical cancer. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sTie-1 concentrations in 75 cervical cancer patients, 40 cervical intraepithelial neoplasia (CIN) patients, and 55 healthy controls without cervical lesions, and sTie-1 levels were compared between the groups. Receiver operating characteristic curves was used to evaluate the diagnostic value of sTie-1. The relationship between sTie-1 concentrations in patients with cervical cancer and clinicopathological features and prognosis were analyzed, and the risk factors for postoperative recurrence were determined using univariate and multivariable Cox proportional hazards regression. Results: We found that sTie-1 concentrations gradually increased according to lesion severity (i.e., cancer vs. CIN; p < 0.05) and were significantly elevated in adenocarcinoma compared with healthy controls. sTie-1 levels strongly distinguished between cervical cancer patients and the healthy controls (area under the curve = 0.846; cut-off value = 1,882.64 pg/ml; sensitivity = 74.6%; specificity = 96.4%). Moreover, sTie-1 levels in cervical cancer patients were significantly associated with tumor size, advanced tumor stage, lymph node metastasis, and reduced 4-years progression-free survival. Cervical cancer patients with high sTie-1 concentrations had a 3.123-fold [95% confidence interval (CI): 1.087–8.971, p = 0.034] higher risk for tumor recurrence. Conclusions: Elevated sTie-1 levels in patients with cervical carcinoma were associated with tumor progression and poor prognosis, indicating that sTie-1 may be a valuable marker for predicting progression and prognosis of cervical cancer.
C1 [Bai, Rui] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Diao, Bowen] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Li, Kaili] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Xu, Xiaohan] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Yang, Ping] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
RP Yang, P (reprint author), Shihezi University, School of Medicine, First Affiliated Hospital, Department of Gynecology, Shihezi, China.
EM pingy2018@163.com
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer J Clinicians, 2018, 68(6): 394–424., DOI 10.3322/caac.21492
Bao HL, Liu YN, Wang LJ, Fang LW, Cong S, Zhou MG, et al. Analysis on Mortality of Cervical Cancer and its Temporal Trend in Women in China, 2006-2012. Zhonghua Liu Xing Bing Xue Za Zhi, 2017, 38(1):58–64., DOI 10.3760/cma.j.issn.0254-6450.2017.01.011
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Liu H, Ye X, Li D, Yao Q, Li Y. Incidence, Clinical Risk and Prognostic Factors for Liver Metastasis in Patients with Cervical Cancer: a Population-Based Retrospective Study. BMC Cancer, 2021, 21(1):421., DOI 10.1186/s12885-021-08127-6
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Yang P, Chen N, Yang D, Crane J, Yang S, Wang H, et al. The Ratio of Serum Angiopoietin-1 to Angiopoietin-2 in Patients with Cervical Cancer Is a Valuable Diagnostic and Prognostic Biomarker. PeerJ, 2017, 5:e3387., DOI 10.7717/peerj.3387
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610006
EP 1610012
DI 10.3389/pore.2021.1610006
PG 7
ER
PT J
AU Hu, F
Guo, L
Yu, J
Dai, D
Xiong, Y
He, Y
Zhou, W
AF Hu, Fangling
Guo, Liang
Yu, Jieqing
Dai, Daofeng
Xiong, Yuanping
He, Yuanqiao
Zhou, Wensheng
TI Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head-and-neck squamous cell carcinoma; drug sensitivity; patient-derived xenograft; anlotinib; tumor inhibition
ID head-and-neck squamous cell carcinoma; drug sensitivity; patient-derived xenograft; anlotinib; tumor inhibition
AB Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end. Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo. Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis. Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.
C1 [Hu, Fangling] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Guo, Liang] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Yu, Jieqing] Jiangxi Institute of Otorhinolaryngology-Head and Neck SurgeryNanchang, China.
[Dai, Daofeng] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Xiong, Yuanping] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[He, Yuanqiao] Nanchang University, Laboratory Animal Science CenterNanchang, China.
[Zhou, Wensheng] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
RP Zhou, W (reprint author), Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck Surgery, Nanchang, China.
EM zhouwesh@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610008
EP 1610016
DI 10.3389/pore.2021.1610008
PG 9
ER
PT J
AU Kobayashi, Y
Kitazono, I
Akahane, T
Yanazume, Sh
Kamio, M
Togami, Sh
Nohara, S
Sakamoto, I
Yokoyama, S
Tabata, K
Kobayashi, H
Tanimoto, A
AF Kobayashi, Yusuke
Kitazono, Ikumi
Akahane, Toshiaki
Yanazume, Shintaro
Kamio, Masaki
Togami, Shinichi
Nohara, Sachio
Sakamoto, Ippei
Yokoyama, Seiya
Tabata, Kazuhiro
Kobayashi, Hiroaki
Tanimoto, Akihide
TI Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE microsatellite instability; tumor mutation burden; integrated molecular diagnosis; endometrial cancers; solid proliferation
ID microsatellite instability; tumor mutation burden; integrated molecular diagnosis; endometrial cancers; solid proliferation
AB It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation (POLEmut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1. Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1, CCNE1, and MYC. CS cases were classified as three TCGA types other than the POLEmut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers.
C1 [Kobayashi, Yusuke] Course of Advanced Cancer Medicine for Gynecologic CancerKagoshima, Japan.
[Kitazono, Ikumi] Kagoshima University Graduate School of Medical and Dental Sciences, Department of PathologyKagoshima, Japan.
[Akahane, Toshiaki] Kagoshima University Graduate School of Medical and Dental Sciences, Department of PathologyKagoshima, Japan.
[Yanazume, Shintaro] Kagoshima University, Field of Oncology, Faculty of Medicine, Department of Obstetrics and Gynecology Department of Molecular and Cellular PathologyKagoshima, Japan.
[Kamio, Masaki] Kagoshima University, Field of Oncology, Faculty of Medicine, Department of Obstetrics and Gynecology Department of Molecular and Cellular PathologyKagoshima, Japan.
[Togami, Shinichi] Kagoshima University, Field of Oncology, Faculty of Medicine, Department of Obstetrics and Gynecology Department of Molecular and Cellular PathologyKagoshima, Japan.
[Nohara, Sachio] Mitsubishi Space Software, Department of Biomedical InformaticsAmagasaki, Japan.
[Sakamoto, Ippei] Mitsubishi Space Software, Department of Biomedical InformaticsAmagasaki, Japan.
[Yokoyama, Seiya] Kagoshima University Graduate School of Medical and Dental Sciences, Department of PathologyKagoshima, Japan.
[Tabata, Kazuhiro] Kagoshima University Graduate School of Medical and Dental Sciences, Department of PathologyKagoshima, Japan.
[Kobayashi, Hiroaki] Course of Advanced Cancer Medicine for Gynecologic CancerKagoshima, Japan.
[Tanimoto, Akihide] Kagoshima University Graduate School of Medical and Dental Sciences, Department of PathologyKagoshima, Japan.
RP Tanimoto, A (reprint author), Kagoshima University Graduate School of Medical and Dental Sciences, Department of Pathology, Kagoshima, Japan.
EM akit09@m3.kufm.kagoshima-u.ac.jp
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610013
EP 1610022
DI 10.3389/pore.2021.1610013
PG 10
ER
PT J
AU Refaat, B
Zekri, J
Aslam, A
Ahmad, J
Baghdadi, M
Meliti, A
Idris, Sh
Sultan, S
Alardati, H
Saimeh, AH
Alsaegh, A
Alhadrami, M
Hamid, T
Naeem, M
Elsamany, ASh
AF Refaat, Bassem
Zekri, Jamal
Aslam, Akhmed
Ahmad, Jawwad
Baghdadi, A. Mohammed
Meliti, Abdelrazak
Idris, Shakir
Sultan, Sufian
Alardati, Hosam
Saimeh, Akram Haitham
Alsaegh, Aiman
Alhadrami, Mai
Hamid, Tahira
Naeem, E. Mohammed
Elsamany, Ahmed Shereef
TI Profiling Activins and Follistatin in Colorectal Cancer According to Clinical Stage, Tumour Sidedness and Smad4 Status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; cell cycle; activin-A; activin-AB; activin-B; follistatin
ID apoptosis; cell cycle; activin-A; activin-AB; activin-B; follistatin
AB This study explored the roles of activins and follistatin in colorectal cancers. Paired malignant and normal colonic tissues were collected from archived paraffin-embedded (n = 90 patients) alongside fresh (n = 40 patients) specimen cohorts. Activin β-subunits, follistatin and Smad4 mRNAs and proteins were measured by real-time PCR and immunohistochemistry (IHC). Mature activin-A, -B, -AB and follistatin proteins were measured by ELISA. Cancer tissues having ≤ the 20th percentile of the Smad4 IHC score were considered as low (L-S4) group. The Smad4-intact SW480 and Smad4-null HT29 colon cancer cell lines were treated with activins and follistatin, and cell cycle was analysed by flow cytometry. The cell cycle inducing (CCND1/CCND3) and inhibitory (p21/ p27) proteins alongside the survival (survivin/BCL2) and pro-apoptosis (Casp-8/Casp-3) markers were measured by immunofluorescence. Thirty-nine patients had right-sided cancers (30%) and showed higher rates of L-S4 tumours (n = 17; 13.1%) alongside worse clinicopathological characteristics relative to left-sided cancers. The βA-subunit and activin-A increased, whilst βB-subunit and activin-AB decreased, in malignant sites and the late-stage cancers revealed the greatest abnormalities. Interestingly, follistatin declined markedly in early-stage malignant tissues, whilst increased significantly in the advanced stages. All activin molecules were comparable between the early stage right- and left-sided tumours, whereas the late-stage right-sided cancers and L-S4 tumours showed more profound deregulations. In vitro, activin-A increased the numbers of the SW480 cells in sub-G1 and G0/G1-phases, whereas reduced the HT29 cell numbers in the sub-G1 phase with simultaneous increases in the G0/G1 and S phases. The p21/p27/Casp-8/ Casp-3 proteins escalated, whilst CCND1/CCND3/BCL2/survivin declined in the SW480 cells following activin-A, whereas activin-A only promoted p21 and p27 alongside reduced CCND3 in the HT29 cells. By contrast, activin-AB increased the numbers of SW480 and HT29 cells in Sub-G1 and G0/G1-phases and promoted the anti-cancer and reduced the oncogenic proteins in both cell lines. In conclusion, activins and follistatin displayed stagedependent dysregulations and were markedly altered during the advanced stages of right-sided and L-S4 cancers. Moreover, the activin-A actions in CRC could be Smad4- dependent, whereas activin-AB may act as a Smad4-independent tumour suppressor protein.
C1 [Refaat, Bassem] Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine DepartmentMakkah, Saudi Arabia.
[Zekri, Jamal] King Faisal Specialist Hospital and Research Centre, Oncology DepartmentJeddah, Saudi Arabia.
[Aslam, Akhmed] Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine DepartmentMakkah, Saudi Arabia.
[Ahmad, Jawwad] Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine DepartmentMakkah, Saudi Arabia.
[Baghdadi, A. Mohammed] King Faisal Specialist Hospital and Research Centre, Research CentreJeddah, Saudi Arabia.
[Meliti, Abdelrazak] King Faisal Specialist Hospital and Research Centre, Pathology DepartmentJeddah, Saudi Arabia.
[Idris, Shakir] Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine DepartmentMakkah, Saudi Arabia.
[Sultan, Sufian] King Faisal Specialist Hospital and Research Centre, Department of SurgeryJeddah, Saudi Arabia.
[Alardati, Hosam] King Faisal Specialist Hospital and Research Centre, Pathology DepartmentJeddah, Saudi Arabia.
[Saimeh, Akram Haitham] King Faisal Specialist Hospital and Research Centre, Department of SurgeryJeddah, Saudi Arabia.
[Alsaegh, Aiman] Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine DepartmentMakkah, Saudi Arabia.
[Alhadrami, Mai] Umm Al-Qura University, Faculty of Medicine, Pathology DepartmentMakkah, Saudi Arabia.
[Hamid, Tahira] King Abdullah Medical City, Histopathology DepartmentMakkah, Saudi Arabia.
[Naeem, E. Mohammed] King Abdullah Medical City, Histopathology DepartmentMakkah, Saudi Arabia.
[Elsamany, Ahmed Shereef] King Abdullah Medical City, Oncology Centre, Medical Oncology DepartmentMakkah, Saudi Arabia.
RP Refaat, B (reprint author), Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine Department, Makkah, Saudi Arabia.
EM bassem.refaat@yahoo.co.uk
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610032
EP 1610051
DI 10.3389/pore.2021.1610032
PG 20
ER
PT J
AU Turkevi-Nagy, S
Bathori,
Bocz, J
Krenacs, L
Cserni, G
Kovari, B
AF Turkevi-Nagy, Sandor
Bathori, Agnes
Bocz, Janos
Krenacs, Laszlo
Cserni, Gabor
Kovari, Bence
TI Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; syntaxin-1; insulinoma-associated protein 1; breast neuroendocrine neoplasms; solid papillary carcinoma; mucinous carcinoma; carcinoma no special type
ID immunohistochemistry; syntaxin-1; insulinoma-associated protein 1; breast neuroendocrine neoplasms; solid papillary carcinoma; mucinous carcinoma; carcinoma no special type
AB Introduction: A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin. We assessed the applicability of two novel markers, syntaxin-1 and insulinoma-associated protein 1 (INSM1) in breast carcinomas. Methods: Hypercellular (Type B) mucinous carcinomas, solid papillary carcinomas, invasive carcinomas of no special type with neuroendocrine features and ductal carcinomas in situ of neuroendocrine subtype were included in our study. The immunohistochemical panel included chromogranin A, synaptophysin, CD56, syntaxin- 1 and INSM1. The specificity of syntaxin-1 and INSM1 was determined using samples negative for chromogranin A, synaptophysin and CD56. Results: The sensitivity of syntaxin-1 was 84.7% (50/59), with diffuse positivity in more than 60% of the cases. Syntaxin-1 also had an excellent specificity (98.1%). Depending on the definition for positivity, the sensitivity of INSM1 was 89.8% (53/59) or 86.4% (51/59), its specificity being 57.4% or 88.9%. The sensitivities of chromogranin A, synaptophysin and CD56 were 98.3, 74.6 and 22.4%, respectively. Discussion: Syntaxin-1 and INSM1 are sensitive and specific markers of breast tumors with neuroendocrine features, outperforming chromogranin A and CD56. We recommend syntaxin-1 and INSM1 to be included in the routine neuroendocrine immunohistochemical panel.
C1 [Turkevi-Nagy, Sandor] University of Szeged, Department of PathologySzeged, Hungary.
[Bathori, Agnes] University of Szeged, Department of PathologySzeged, Hungary.
[Bocz, Janos] University of Szeged, Department of PathologySzeged, Hungary.
[Krenacs, Laszlo] Bay Zoltan Foundation for Applied Research, Institute for Biotechnology, Laboratory of Tumor Pathology and Molecular DiagnosticsSzeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of PathologySzeged, Hungary.
[Kovari, Bence] University of Szeged, Department of PathologySzeged, Hungary.
RP Turkevi-Nagy, S (reprint author), University of Szeged, Department of Pathology, Szeged, Hungary.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610039
EP 1610045
DI 10.3389/pore.2021.1610039
PG 7
ER
PT J
AU Kiss, Z
Bogos, K
Tamasi, L
Ostoros, Gy
Muller, V
Urban, L
Bittner, N
Sarosi, V
Vastag, A
Polanyi, Z
Nagy-Erdei, Zs
Knollmajer, K
Varnai, M
Nagy, B
Horvath, K
Rokszin, Gy
Abonyi-Toth, Zs
Barcza, Zs
Moldvay, J
Galffy, G
Voko, Z
AF Kiss, Zoltan
Bogos, Krisztina
Tamasi, Lilla
Ostoros, Gyula
Muller, Veronika
Urban, Laszlo
Bittner, Nora
Sarosi, Veronika
Vastag, Aladar
Polanyi, Zoltan
Nagy-Erdei, Zsofia
Knollmajer, Kata
Varnai, Mate
Nagy, Balazs
Horvath, Krisztian
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Barcza, Zsofia
Moldvay, Judit
Galffy, Gabriella
Voko, Zoltan
TI Increase in the Length of Lung Cancer Patient Pathway Before First-Line Therapy: A 6-Year Nationwide Analysis From Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; patient pathway; time to treatment; episode of care; system interval
ID lung cancer; patient pathway; time to treatment; episode of care; system interval
AB Objective: This study aimed to examine the characteristics of the lung cancer (LC) patient pathway in Hungary during a 6-years period. Methods: This nationwide, retrospective study included patients newly diagnosed with LC (ICD-10 C34) between January 1, 2011, and December 31, 2016, using data from the National Health Insurance Fund (NHIF) of Hungary. The following patient pathway intervals were examined: system, diagnostic and treatment interval by age, gender, tumor type, study year and first-line LC therapy. Results: During the 6-years study period, 17,386 patients had at least one type of imaging (X-ray or CT/MRI) prior to diagnosis, and 12,063 had records of both X-ray and CT/MRI. The median system interval was 64.5 days, and it was 5 days longer among women, than in men (68.0 vs. 63.0 days). The median system interval was significantly longer in patients with adenocarcinoma compared to those with squamous cell carcinoma or small cell lung cancer (70.4 vs. 64.0 vs. 48.0 days, respectively). Patients who received surgery as firstline treatment had significantly longer median system intervals compared to those receiving chemotherapy (81.4 vs. 62.0 days). The median system interval significantly increased from 62.0 to 66.0 days during the 6-years study period. Conclusion: The LC patient pathway significantly increased in Hungary over the 6-years study period. There were no significant differences in the length of the whole LC patient pathway according to age, however, female sex, surgery as first-line treatment, and adenocarcinoma were associated with longer system intervals.
C1 [Kiss, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Ostoros, Gyula] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Urban, Laszlo] Matrahaza Healthcare Center and University Teaching HospitalMatrahaza, Hungary.
[Bittner, Nora] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of MedicinePecs, Hungary.
[Vastag, Aladar] MSD Pharma Hungary Kft.Budapest, Hungary.
[Polanyi, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy-Erdei, Zsofia] MSD Pharma Hungary Kft.Budapest, Hungary.
[Knollmajer, Kata] MSD Pharma Hungary Kft.Budapest, Hungary.
[Varnai, Mate] MSD Pharma Hungary Kft.Budapest, Hungary.
[Nagy, Balazs] Semmelweis University, Center for Health Technology AssessmentBudapest, Hungary.
[Horvath, Krisztian] Semmelweis University, Center for Health Technology AssessmentBudapest, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Barcza, Zsofia] Syntesia LtdBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Semmelweis University, Ist Department of PulmonologyBudapest, Hungary.
[Galffy, Gabriella] County Hospital of PulmonologyTorokbalint, Hungary.
[Voko, Zoltan] Semmelweis University, Center for Health Technology AssessmentBudapest, Hungary.
RP Kiss, Z (reprint author), MSD Pharma Hungary Kft., Budapest, Hungary.
EM zoltan_kiss2@merck.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610041
EP 1610051
DI 10.3389/pore.2021.1610041
PG 11
ER
PT J
AU Forika, G
Kiss,
Petovari, G
Danko, T
Gellert, BA
Krenacs, T
AF Forika, Gertrud
Kiss, Eva
Petovari, Gabor
Danko, Titanilla
Gellert, Bertram Aron
Krenacs, Tibor
TI Modulated Electro-Hyperthermia Supports the Effect of Gemcitabine Both in Sensitive and Resistant Pancreas Adenocarcinoma Cell Lines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; cell cycle arrest; pancreas adenocarcinoma; modulated electro-hyperthermia; gemcitabine resistance; combined treatment
ID apoptosis; cell cycle arrest; pancreas adenocarcinoma; modulated electro-hyperthermia; gemcitabine resistance; combined treatment
AB The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is frequently associated to high treatment resistance. Gemcitabine (GEM) alone or in combination is the most used chemotherapy for unresecable PDACs. Here we studied whether modulated electrohyperthermia (mEHT), a non-invasive complementary treatment, can support the effect of GEM on PDAC cells in vitro. The LD20 for the GEM-resistant Panc1 cells proved to be 200× higher than for the drug-sensitive Capan1. The mEHT alone caused significant apoptosis in Capan1 cultures as confirmed by the elevated SubG1 phase cell fraction and increased number of cleaved Caspase-3 positive cells 48 h after treatment, with an additive effect when GEM was used after hyperthermia. These were accompanied by reduced number of G1, S, and G2/M phase cells and elevated expression of the cyclindependent kinase inhibitor p21waf1 protein. In GEM-resistant Panc1 cells, an initial apoptosis was detected by flow cytometry 24 h after mEHT ± GEM treatment, which however diminished by 48 h at persistent number of cleaved Caspase-3 positive tumor cells. Though GEM monotherapy reduced the number of tumor progenitor colonies in Capan1 cell line, an additive colony inhibitory effect of mEHT was observed after mEHT + GEM treatment. The heat shock induced Hsp27 and Hsp70 proteins, which are known to sensitize PDAC cells to GEM were upregulated in both Capan1 and Panc1 cells 24 h after mEHT treatment. The level of E-Cadherin, a cell adhesion molecule, increased in Capan1 cells after mEHT + GEM treatment. In conclusion, in GEM-sensitive PDAC cells mEHT treatment alone induced cell death and cell cycle inhibition and improved GEM efficiency in combination, which effects were milder and short-term up to 24 h in the GEM-resistant Panc1 cells. Our data further support the inclusion of hyperthermia, in particular of mEHT, into the traditional oncotherapy regimens of PDAC.
C1 [Forika, Gertrud] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kiss, Eva] Semmelweis University, 1st Department of Internal Medicine and Oncology, Oncology ProfileBudapest, Hungary.
[Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Gellert, Bertram Aron] Orszagos Onkologiai Intezet, Mellkassebeszeti OsztalyBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Krenacs, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM krenacs.tibor@med.semmelweis-univ.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610048
EP 1610062
DI 10.3389/pore.2021.1610048
PG 15
ER
PT J
AU Deng, Y
Yu, L
Zhao, Y
Peng, J
Xu, Y
Qin, J
Xiao, B
Liu, S
Li, M
Fang, Y
Pan, Z
AF Deng, Yuxiang
Yu, Long
Zhao, Yujie
Peng, Jianhong
Xu, Yanbo
Qin, Jiayi
Xiao, Binyi
Liu, Songran
Li, Mei
Fang, Yujing
Pan, Zhizhong
TI RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; expression; RCC1; colorectal liver oligometastases; pathway
ID prognosis; expression; RCC1; colorectal liver oligometastases; pathway
AB Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guaninenucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs). Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored. Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including “Myc targets,” “E2F targets” and “DNA repair” pathways. Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.
C1 [Deng, Yuxiang] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Yu, Long] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Zhao, Yujie] Peking University Shenzhen Hospital, Department of Radiation OncologyShenzhen, China.
[Peng, Jianhong] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Xu, Yanbo] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Qin, Jiayi] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Xiao, Binyi] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Liu, Songran] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of PathologyGuangzhou, China.
[Li, Mei] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of PathologyGuangzhou, China.
[Fang, Yujing] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
[Pan, Zhizhong] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal SurgeryGuangzhou, China.
RP Pan, Z (reprint author), Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Colorectal Surgery, Guangzhou, China.
EM panzhzh@sysucc.org.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD DEC
PY 2021
VL 27
IS 4
BP 1610077
EP 1610086
DI 10.3389/pore.2021.1610077
PG 10
ER
PT J
AU Bienkiewicz, J
Smolarz, B
Wilczynski, M
Stepowicz, A
Jablonski, G
Oblekowska, A
Malinowski, A
Romanowicz, H
AF Bienkiewicz, Jan
Smolarz, Beata
Wilczynski, Milosz
Stepowicz, Anna
Jablonski, Grzegorz
Oblekowska, Anna
Malinowski, Andrzej
Romanowicz, Hanna
TI Is Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) Associated With Uterine Leiomyomas? A Pilot Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE single nucleotide polymorphism; obesity; uterine leiomyomas; uterine fibroids; c.276 G>T; adiponectin; ADIPOQ; (NM_004797.4):c.214+62G>T
ID single nucleotide polymorphism; obesity; uterine leiomyomas; uterine fibroids; c.276 G>T; adiponectin; ADIPOQ; (NM_004797.4):c.214+62G>T
AB Objective: Although polymorphisms of adiponectin gene (ADIPOQ) in obesity-related conditions have been the target of research efforts, little is known about this genetic marker in uterine leiomyomas. The aim of this pilot study was to analyze the frequencies of alleles and genotypes of Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and to correlate it with the risk of uterine fibroids. Study Design: The Test Group comprised 90 women treated surgically for uterine leiomyomas in the Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, PolishMother’sMemorial Hospital-Research Institute. 90 disease-free individuals were used as Controls. Patients within both groups were additionally stratified into lean, overweight and obese, according to Body Mass Index. Statistical analysis was performed between the two major groups and, furthermore, within the abovementioned subgroups. Results: The study revealed no statistically significant differences in the distribution of alleles and genotypes of SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) between the two main groups. A weak correlation within distributions of alleles was observed between obese Test Patients and lean Controls. Conclusion: This pilot study has revealed no association between SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and uterine fibroids. Further studies on larger groups are warranted to elucidate whether this SNP may be correlated with uterine leiomyomas.
C1 [Bienkiewicz, Jan] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
[Smolarz, Beata] Polish Mothers’ Memorial Hospital-Research Institute, Department of Pathology, Laboratory of Molecular GeneticsLodz, Poland.
[Wilczynski, Milosz] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
[Stepowicz, Anna] Polish Mother’s Memorial Hospital- Research Institute, Department of Obstetrics, Perinatology and GynecologyLodz, Poland.
[Jablonski, Grzegorz] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
[Oblekowska, Anna] Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic OncologyLodz, Poland.
[Malinowski, Andrzej] Medical University of Lodz, Department of Operative and Endoscopic GynecologyLodz, Poland.
[Romanowicz, Hanna] Polish Mothers’ Memorial Hospital-Research Institute, Department of PathologyLodz, Poland.
RP Bienkiewicz, J (reprint author), Polish Mothers’ Memorial Hospital-Research Institute, Department of Surgical & Endoscopic Gynecology and Gynecologic Oncology, Lodz, Poland.
EM jan.bienkiewicz@iczmp.edu.pl
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1609966
EP 1609972
DI 10.3389/pore.2021.1609966
PG 7
ER
PT J
AU Li, Z
Zhao, Z
Wang, Ch
Wang, D
Mao, H
Liu, F
Yang, Y
Tao, F
Lu, Z
AF Li, Zhiheng
Zhao, Zhenhua
Wang, Chuchu
Wang, Dandan
Mao, Haijia
Liu, Fang
Yang, Ye
Tao, Feng
Lu, Zengxin
TI Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EGFR; VEGF; advanced gastric cancer; DCE-MRI; histogram parameters
ID EGFR; VEGF; advanced gastric cancer; DCE-MRI; histogram parameters
AB Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC). Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score. Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p < 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively). Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.
C1 [Li, Zhiheng] Shaoxing University School of MedicineShaoxing, China.
[Zhao, Zhenhua] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of RadiologyShaoxing, China.
[Wang, Chuchu] Shaoxing University School of MedicineShaoxing, China.
[Wang, Dandan] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of RadiologyShaoxing, China.
[Mao, Haijia] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of RadiologyShaoxing, China.
[Liu, Fang] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of PathologyShaoxing, China.
[Yang, Ye] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of PathologyShaoxing, China.
[Tao, Feng] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of Gastrointestinal SurgeryShaoxing, China.
[Lu, Zengxin] Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of RadiologyShaoxing, China.
RP Lu, Z (reprint author), Zhejiang University School of Medicine, Shaoxing People’s Hospital, Shaoxing Hospital, Department of Radiology, Shaoxing, China.
EM luzx777@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610001
EP 1610012
DI 10.3389/pore.2021.1610001
PG 12
ER
PT J
AU Deme, D
Kovacs, S
Telekes, A
AF Deme, Daniel
Kovacs, Sandor
Telekes, Andras
TI Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE overall survival; advanced cancer; serum biomarkers; prognostic importance; CRP; albumin; PLR
ID overall survival; advanced cancer; serum biomarkers; prognostic importance; CRP; albumin; PLR
AB Introduction: Consistent association between elevated baseline serumvalues and C-reactive protein (CRP), cross-linked fibrin degradation products (D-dimer), lactate dehydrogenase (LDH), decreased baseline serum albumin, absolute lymphocyte count to absolute monocyte count ratio (LMR), elevated absolute neutrophil count to absolute lymphocyte count ratio (NLR), elevated platelet count to absolute lymphocyte count ratio (PLR), and between some combinations of these biomarkers and the short overall survival of patients with malignant diseases has already been reported. These biomarkers are independent prognostic factors for cancer. Here, the most significant biomarker combination of these values was searched and studied in real-life advanced cancer patients of a single center. Methods: The authors retrospectively analyzed the association of the aforementioned biomarkers and their combination and OS of 75 consecutive cancer patients with locally advanced, recurrent, or metastatic diseases. Validated cut-off determination was used. Results: CRP, albumin, and PLR showed marked association with OS. Cut-off values for significant shorter OS were 30.65 mg/L (p < 0.001), 44.35 g/L (p < 0.001), and 168.20 (p < 0.001), respectively. Based on assessed biomarker cut-offs, four patient groups were created to determine whether biomarker values were out of range (ORV) compared to cutoff: 1) No ORV biomarkers (n = 24; OS = 26.07 months); 2) one ORV biomarker (n = 21; OS = 13.50 months); 3) two ORV biomarkers (n = 20; OS = 7.97 months), and 4) three ORV biomarkers (n = 10; OS = 3.91 months). Significant differences in OS were detected between the groups: For 1. vs. 2. hazard ratio (HR) = 3.0 (95% CI: 1.5–6.2), p = 0.003; for 1. vs. 3. HR = 4.1 (95% CI: 2.0–8.3), p < 0.001; and for 1. vs. 4. HR = 10.2 (95% CI: 4.2–24.6), p < 0.001. Conclusion: Based on our analysis, we can confirm that the complex monitoring of CRP, albumin, and PLR would provide a good estimation of OS. Large scale prospective studies are warranted to explore this and other useful combinations of prognostic biomarkers and their relationship to the well-established prognostic systems in real-life.
C1 [Deme, Daniel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Kovacs, Sandor] University of Debrecen, Department of Economical and Financial MathematicsDebrecen, Hungary.
[Telekes, Andras] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
RP Deme, D (reprint author), Szent Lazar Megyei Korhaz, Onkologiai Osztaly, Salgotarjan, Hungary.
EM danieldeme_md@ymail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610004
EP 1610012
DI 10.3389/pore.2022.1610004
PG 9
ER
PT J
AU Yao, JM
Zhao, JY
Lv, FF
Yang, XB
Wang, HJ
AF Yao, Jin-Ming
Zhao, Jun-Yu
Lv, Fang-Fang
Yang, Xue-Bo
Wang, Huan-Jun
TI A Potential Nine-lncRNAs Signature Identification and Nomogram Diagnostic Model Establishment for Papillary Thyroid Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE risk score; WGCNA; papillary thyroid cancer; lncRNAs; LASSO
ID risk score; WGCNA; papillary thyroid cancer; lncRNAs; LASSO
AB The purpose of our current study was to establish a long non-coding RNA(lncRNA) signature and assess its prognostic and diagnostic power in papillary thyroid cancer (PTC). LncRNA expression profiles were obtained from the Cancer Genome Atlas (TCGA). The key module and hub lncRNAs related to PTC were determined by weighted gene coexpression network analysis (WGCNA) and LASSO Cox regression analyses, respectively. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis were implemented to analyze the possible biological processes and signaling pathways of hub lncRNAs. Associations between key lncRNA expressions and tumor-infiltrating immune cells were identified using the TIMER website, and proportions of immune cells in high/low risk score groups were compared. Kaplan-Meier Plotter was used to evaluate the prognostic significance of hub genes in PTC. A diagnostic model was conducted with logistic regression analysis, and its diagnostic performance was assessed by calibration/ receiver operating characteristic curves and principal component analysis. A nine-lncRNAs signature (SLC12A5-AS1, LINC02028, KIZ-AS1, LINC02019, LINC01877, LINC01444, LINC01176, LINC01290, and LINC00581) was established in PTC, which has significant diagnostic and prognostic power. Functional enrichment analyses elucidated the regulatory mechanism of the nine-lncRNAs signature in the development of PTC. This signature and expressions of nine hub lncRNAs were correlated with the distributions of tumor infiltrating immune cells. A diagnostic nomogram was also established for PTC. By comparing with the published models with less than or equal to nine lncRNAs, our signature showed a preferable performace for prognosis prediction. In conclusion, our present research established an innovative nine-lncRNAs signature and a six-lncRNAs nomogram that might act as a potential indicator for PTC prognosis and diagnosis, which could be conducive to the PTC treatment.
C1 [Yao, Jin-Ming] The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Department of Endocrinology and MetabologyJinan, China.
[Zhao, Jun-Yu] The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Department of Endocrinology and MetabologyJinan, China.
[Lv, Fang-Fang] The 960th hospital of the PLA Joint Logistics Support Force, Department of Endocrinology and MetabologyJinan, China.
[Yang, Xue-Bo] Beijing Splinger Institute of MedicineJinan, China.
[Wang, Huan-Jun] The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Department of Endocrinology and MetabologyJinan, China.
RP Wang, HJ (reprint author), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Department of Endocrinology and Metabology, Jinan, China.
EM huanjun-w@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610012
EP 1610026
DI 10.3389/pore.2022.1610012
PG 15
ER
PT J
AU Zhang, X
Ma, H
Zhang, L
Li, F
AF Zhang, Xuefeng
Ma, Hongfu
Zhang, Liang
Li, Fenghuan
TI Predictive Role of Tumor-Stroma Ratio for Survival of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE recurrence; survival; meta-analysis; non-small cell lung cancer; tumor-stroma ratio
ID recurrence; survival; meta-analysis; non-small cell lung cancer; tumor-stroma ratio
AB Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and metaanalysis was conducted to summarize current evidence for the role of TSR in NSCLC. Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and metaregression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the metaanalysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = −0.012, p = 0.03) and OS (Coefficient = −0.013, p = 0.04), respectively. Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.
C1 [Zhang, Xuefeng] Yantai Mountain Hospital, Department of Respiratory and Critical Care MedicineYantai, China.
[Ma, Hongfu] Yantai Mountain Hospital, Department of Respiratory and Critical Care MedicineYantai, China.
[Zhang, Liang] Yantai Mountain Hospital, Department of Respiratory and Critical Care MedicineYantai, China.
[Li, Fenghuan] Yantai Mountain Hospital, Department of Respiratory and Critical Care MedicineYantai, China.
RP Li, F (reprint author), Yantai Mountain Hospital, Department of Respiratory and Critical Care Medicine, Yantai, China.
EM lifenghuan_255@21cn.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610021
EP 1610032
DI 10.3389/pore.2021.1610021
PG 12
ER
PT J
AU Xie, Y
Fu, R
Xiao, Z
Li, G
AF Xie, Yan
Fu, Ruimin
Xiao, Zheng
Li, Gang
TI A Risk Model Based on Immune-Related Genes Predicts Prognosis and Characterizes the Immune Landscape in Esophageal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; chemotherapy; prognosis; esophageal cancer; immune-related genes; risk model
ID immunotherapy; chemotherapy; prognosis; esophageal cancer; immune-related genes; risk model
AB Aberrant immune gene expression has been shown to have close correlations with the occurrence and progression of esophageal cancer (EC). We aimed to generate a prognostic signature based on immune-related genes (IRGs) capable of predicting prognosis, immune checkpoint gene (ICG) expressions, and half-inhibitory concentration (IC50) for chemotherapy agents for EC patients. Transcriptome, clinical, and mutation data on tumorous and paratumorous tissues from EC patients were collected from The Cancer Genome Atlas (TCGA) database. Then, we performed differential analysis to identify IRGs differentially expressed in EC. Their biofunctions and related pathways were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These gene expression profiling data were merged with survival information and subjected to univariate Cox regression to select prognostic genes, which were then included in a Lasso-Cox model for signature generation (risk score calculation). Patients were divided into the high- and low-risk groups using the median risk score as a cutoff. The accuracy of the signature in overall survival prediction was assessed, so were its performances in predicting ICG expressions and IC50 for chemotherapy and targeted therapy agents and immune cell landscape characterization. Fifteen prognostic IRGs were identified, seven of which were optimal for risk score calculation. As expected, high-risk patients had worse overall survival than low-risk individuals. Significant differences were found in tumor staging, immune cell infiltration degree, frequency of tumor mutations, tumor mutation burden (TMB), and immune checkpoint gene expressions between high- vs. low-risk patients. Further, high-risk patients exhibited high predicted IC50 for paclitaxel, cisplatin, doxorubicin, and erlotinib compared to low-risk patients. The seven-IRG-based signature can independently and accurately predict overall survival and tumor progression, characterize the tumor immune microenvironment (TIME) and estimate ICG expressions and IC50 for antitumor therapies. It shows the potential of guiding personalized treatment for EC patients.
C1 [Xie, Yan] Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical LaboratoryZhengzhou, China.
[Fu, Ruimin] Henan Finance University, College of Health ManagementZhengzhou, China.
[Xiao, Zheng] Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical LaboratoryZhengzhou, China.
[Li, Gang] Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical LaboratoryZhengzhou, China.
RP Li, G (reprint author), Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical Laboratory, Zhengzhou, China.
EM gangli086@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610030
EP 1610042
DI 10.3389/pore.2022.1610030
PG 13
ER
PT J
AU Long, C
Xu, Qb
Ding, L
Huang, Lj
Ji, Y
AF Long, Cong
Xu, Qiu-bo
Ding, Li
Huang, Li-juan
Ji, Yong
TI Circular RNAs as Diagnostic and Prognostic Indicators of Colorectal Cancer: A Pooled Analysis of Individual Studies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; circular RNA; diagnosis; prognosis; pooled analysis
ID colorectal cancer; circular RNA; diagnosis; prognosis; pooled analysis
AB Background: Circular RNAs (circRNAs) have proven as a special subset of endogenous RNAs that are implicated in the tumorigenesis of various cancers. This study sought to evaluate the role of circRNAs in the diagnosis and prognosis of colorectal cancer (CRC). Methods: The online databases were searched for collecting relevant studies on circRNAs as diagnostic and prognostic biomarkers of CRC. Two researchers independently screened literature, extracted data, and evaluated the bias and risks of included studies. The diagnostic and prognostic indicatorsweremerged and analyzed using STATA 12.0 software, and sources of heterogeneity were traced by the sensitivity analysis and the meta-regression test. Results: A total of 29 articles representing 2639 CRC patients were included. The pooled sensitivity, specificity, and area under the curve (AUC) of circRNAs in differentiating CRC from non-tumor control were 0.75 (95% CI: 0.69–0.80) and 0.74 (95% CI: 0.69–0.78) and 0.81, respectively. The survival analysis showed that up-regulations of up-regulated circRNAs were significantly related to dismal survival inCRCpatients (HR = 2.38, p < 0.001). A stratified analysis showed that the comprehensive diagnostic value of up-regualted circRNAs in CRC was higher than that of down-regualted circRNAs (AUC: 0.83 vs. 0.77; Z test, p < 0.05). The efficacy of tissue-derived circRNAs in the diagnosis of CRC was equal to that of plasma/serum-derived ones (AUC: 0.81 vs. 0.82; Z test, p > 0.05). Conclusion: Abnormally expressed circRNAs as auxiliary biomarkers present underlying value in the diagnosis and prognosis prediction of CRC.
C1 [Long, Cong] Jingjiang People’s Hospital, Department of Clinical LaboratoryTaizhou, China.
[Xu, Qiu-bo] Jingjiang People’s Hospital, Department of Clinical LaboratoryTaizhou, China.
[Ding, Li] Jingjiang People’s Hospital, Department of Clinical LaboratoryTaizhou, China.
[Huang, Li-juan] Jingjiang People’s Hospital, Department of Clinical LaboratoryTaizhou, China.
[Ji, Yong] Jingjiang People’s Hospital, Department of General SurgeryTaizhou, China.
RP Ji, Y (reprint author), Jingjiang People’s Hospital, Department of General Surgery, Taizhou, China.
EM jjrmyongji@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610037
EP 1610048
DI 10.3389/pore.2022.1610037
PG 12
ER
PT J
AU Wang, B
Sun, Y
AF Wang, Bingqi
Sun, Yufu
TI SELPLG Expression Was Potentially Correlated With Metastasis and Prognosis of Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; metastasis; osteosarcoma; SELPLG
ID biomarker; prognosis; metastasis; osteosarcoma; SELPLG
AB Background: Osteosarcoma (OS) is the most prevalent malignant primary bone tumor in children. Selectin P ligand gene (SELPLG) has been studied in several cancers. Our research aimed to explore the role of SELPLG in OS. Methods: All OS patient data was obtained from TARGET and GEO databases. Differential expression analyses were conducted in limma package of R. Functional analyses included GO and KEGG enrichment analyses. Immune cell infiltration analysis was done in CIBERSORT software. The overall survival was calculated using survival and survminer package of R. Results: Significantly lower SELPLG expression was observed in metastatic OS samples compared with non-metastatic OS samples, both in TARGET and in GSE21257. Low SELPLG expression was an independent undesirable prognostic factor for OS patients, in both TARGET and GEO datasets. Totally 62 differentially expressed gene (DEG) overlaps were found between high SELPLG vs. low SELPLG and non-metastatic vs. metastatic OS samples, affecting metastases and thereby influencing the prognosis, which were significantly enriched in 40 GO and six KEGG terms. Five types of immune cells were significantly differentially infiltrated between high and low SELPLG expression OS patients. Conclusion: SELPLG is closely correlated with metastases and prognosis of OS patients. The OS patients with low SELPLG expression have relatively poorer prognosis and SELPLG is a potential prognostic biomarker for OS.
C1 [Wang, Bingqi] Tianjin First Central Hospital, Department of Orthopedic SurgeryTianjin, China.
[Sun, Yufu] Tianjin First Central Hospital, Department of Orthopedic SurgeryTianjin, China.
RP Sun, Y (reprint author), Tianjin First Central Hospital, Department of Orthopedic Surgery, Tianjin, China.
EM sunyftj@outlook.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610047
EP 1610055
DI 10.3389/pore.2022.1610047
PG 9
ER
PT J
AU Tuncer, BS
Celik, B
Odemis, AD
Erciyas, KS
Erdogan, SO
Avsar, M
Turkcan, KG
Yazici, H
AF Tuncer, Bugra Seref
Celik, Betul
Odemis, Akdeniz Demet
Erciyas, Kilic Seda
Erdogan, Sukruoglu Ozge
Avsar, Mukaddes
Turkcan, Kuru Gozde
Yazici, Hulya
TI miRNA Sequence Analysis in Patients With Kaposi’s Sarcoma-Associated Herpesvirus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; diagnosis; Kaposi’s sarcoma; Virus; KSHV; miRNA-seq
ID prognosis; diagnosis; Kaposi’s sarcoma; Virus; KSHV; miRNA-seq
AB MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi’s sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi’s sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi’s sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi’s sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b- 3p) which have not been described in the literature in the context of Kaposi’s sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi’s sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi’s sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.
C1 [Tuncer, Bugra Seref] Istanbul University, Istanbul Faculty of Medicine, Oncology Institute, Department of Cancer GeneticsIstanbul, Turkey.
[Celik, Betul] Istanbul University, Istanbul Faculty of Medicine, Oncology Institute, Department of Cancer GeneticsIstanbul, Turkey.
[Odemis, Akdeniz Demet] Istanbul University, Istanbul Faculty of Medicine, Oncology Institute, Department of Cancer GeneticsIstanbul, Turkey.
[Erciyas, Kilic Seda] Istanbul University, Istanbul Faculty of Medicine, Oncology Institute, Department of Cancer GeneticsIstanbul, Turkey.
[Erdogan, Sukruoglu Ozge] Istanbul University, Istanbul Faculty of Medicine, Oncology Institute, Department of Cancer GeneticsIstanbul, Turkey.
[Avsar, Mukaddes] T.C. Istanbul Aydin University, Health Services Vocational School of Higher EducationIstanbul, Turkey.
[Turkcan, Kuru Gozde] Halic University, Faculty of Arts and Sciences, Department of Molecular Biology and GeneticsIstanbul, Turkey.
[Yazici, Hulya] Istanbul Arel University, Arel Medical Faculty, Department of Medical Biology and GeneticsIstanbul, Turkey.
RP Yazici, H (reprint author), Istanbul Arel University, Arel Medical Faculty, Department of Medical Biology and Genetics, Istanbul, Turkey.
EM hy2188@istanbul.edu.tr@email.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610055
EP 1610064
DI 10.3389/pore.2022.1610055
PG 10
ER
PT J
AU Zhang, ChL
Fan, K
Gao, MQ
Pang, B
AF Zhang, Chuan-Long
Fan, Kui
Gao, Meng-Qi
Pang, Bo
TI Prognostic Value of Glasgow Prognostic Score in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE meta-analysis; non-small cell lung cancer; systematic review; prognostic; GPS
ID meta-analysis; non-small cell lung cancer; systematic review; prognostic; GPS
AB Background: Systemic inflammation is a key factor in tumor growth. The Glasgow Prognostic Score (GPS) has a certain value in predicting the prognosis of lung cancer. However, these results still do not have a unified direction. Methods: A systematic review and meta-analysis were performed to investigate the relationship between GPS and the prognosis of patients with non-small cell lung cancer (NSCLC). We set patients as follows: GPS = 0 vs. GPS = 1 or 2, GPS = 0 vs. GPS = 1, GPS = 0 vs. GPS = 2. We collected the hazard ratio (HR) and the 95% confidence interval (CI). Results: A total of 21 studies were included, involving 7333 patients. We observed a significant correlation with GPS and poor OS in NSCLC patients (HRGPS=0 vs. GPS=1 or 2 = 1.62, 95% CI: 1.27–2.07, p ≤ .001; HRGPS=0 vs GPS=1 = 2.14, 95% CI:1.31–3.49, p ≤ .001; HRGPS=0 vs. GPS=2 = 2.64, 95% CI: 1.45–4.82, p ≤ .001). Moreover, we made a subgroup analysis of surgery and stage. The results showed that when divided into GPS = 0 group and GPS = 1 or 2 group, the effect of high GPS on OS was more obvious in surgery (HR = 1.79, 95% CI: 1.08–2.97, p = .024). When GPS was divided into two groups (GPS = 0 and GPS = 1 or 2), the III-IV stage, higher GPS is associated with poor OS (HR = 1.73, 95% CI: 1.43–2.09, p ≤ .001). In the comparison of GPS = 0 and GPS = 1 group (HR = 1.56, 95% CI: 1.05–2.31, p = .026) and the grouping of GPS = 0 and GPS = 2(HR = 2.23, 95% CI: 1.17–4.26, p = .015), we came to the same conclusion. Conclusion: For patients with NSCLC, higher GPS is associated with poor prognosis, and GPS may be a reliable prognostic indicator. The decrease of GPS after pretreatment may be an effective way to improve the prognosis of NSCLC.
C1 [Zhang, Chuan-Long] China Academy of Chinese Medical Sciences, Guang’anmen Hospital, International Medical DepartmentBeijing, China.
[Fan, Kui] Integrated TCM-WM Hebei, Cangzhou Hospital, Department of Radiation OncologyCangzhou, China.
[Gao, Meng-Qi] Shandong University of Traditional Chinese Medicine, College of Traditional Chinese MedicineJinan, China.
[Pang, Bo] China Academy of Chinese Medical Sciences, Guang’anmen Hospital, International Medical DepartmentBeijing, China.
RP Pang, B (reprint author), China Academy of Chinese Medical Sciences, Guang’anmen Hospital, International Medical Department, Beijing, China.
EM pangbotommy@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610109
EP 1610118
DI 10.3389/pore.2022.1610109
PG 10
ER
PT J
AU Liang, Y
Wang, T
Gao, R
Jia, X
Ji, T
Shi, P
Xue, J
Yang, A
Chen, M
Han, P
AF Liang, Yiqian
Wang, Ting
Gao, Rui
Jia, Xi
Ji, Ting
Shi, Puyu
Xue, Jianjun
Yang, Aimin
Chen, Mingwei
Han, Peng
TI Fucosyltransferase 8 is Overexpressed and Influences Clinical Outcomes in Lung Adenocarcinoma Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE FUT8; lung adenocarcinoma; bioinformatics analysis; prognosis; proliferation
ID FUT8; lung adenocarcinoma; bioinformatics analysis; prognosis; proliferation
AB Background: Lung adenocarcinoma (LUAD), the most prevalent type of lung cancer, is often metastatic and has a poor prognosis. Recent studies have demonstrated an important role for fucosyltransferase 8 (FUT8) in carcinogenesis and cancer progression. Methods: A meta-analysis with 15 eligible datasets from Gene Expression Omnibus (GEO) was performed to explore the expression of FUT8 in LUAD. The results were further verified in The Cancer Genome Atlas (TCGA) database, followed by survival analysis using Kaplan-Meier plotter. We also validated the protein expression of FUT8 by immunohistochemistry (IHC). In vitro experiments were conducted to determine the biological effects of FUT8 in LUAD cells. Results: The meta-analysis showed the FUT8 expression in LUAD tissues was significantly higher than those in normal lung tissues [standard mean difference (SMD): 1.40; 95% confidence interval (CI): .95–1.85]. The results of TCGA database verified the expression of FUT8 increased in LUAD tissues versus normal tissues. IHC analyses indicated that the protein levels of FUT8 were up-regulated in LUAD, and elevated FUT8 expression was significantly correlated with poor prognosis in LUAD patients. Multivariable Cox regression analysis revealed that FUT8 expression was an independent prognostic factor. Besides, in vitro experiments showed that knockdown of FUT8 in LUAD cells markedly restrained cell proliferation, and stimulated cell apoptosis. Conclusion: This study indicates that increased FUT8 expression is correlated with shortened survival of LUAD patients and might favor the progression of the disease.
C1 [Liang, Yiqian] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Wang, Ting] Xi’an No. 4 Hospital, Department of Respiratory MedicineXi’an, China.
[Gao, Rui] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Jia, Xi] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Ji, Ting] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Shi, Puyu] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Respiratory and Critical Care MedicineXi’an, China.
[Xue, Jianjun] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Yang, Aimin] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Nuclear MedicineXi’an, China.
[Chen, Mingwei] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Respiratory and Critical Care MedicineXi’an, China.
[Han, Peng] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Otolaryngology-Head and Neck SurgeryXi’an, China.
RP Han, P (reprint author), The First Affiliated Hospital of Xi’an Jiaotong University, Department of Otolaryngology-Head and Neck Surgery, Xi’an, China.
EM penghanent@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610116
EP 1610127
DI 10.3389/pore.2022.1610116
PG 12
ER
PT J
AU Micsik, T
Jakab, A
Lehoczki, Cs
Patai,
AF Micsik, Tamas
Jakab, Anna
Lehoczki, Csaba
Patai, V. Arpad
TI Traditional Serrated Adenoma of the Gallbladder, a Case Report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE traditional serrated adenoma; gallbladder; dysplasia; serrated-pathway; TSA
ID traditional serrated adenoma; gallbladder; dysplasia; serrated-pathway; TSA
AB While overwhelming majority of laparoscopic cholecystectomy specimens performed for gallstones or cholecystitis show rather typical findings, sometimes polypoid structures are also removed. These can be related to cholesterolosis or conventional adenomas, but occasionally extraordinary findings do emerge. In our case, a 67-year old lady with typical complaints of cholecystitis underwent routine laparoscopic cholecystectomy. Preoperative ultrasound revealed a polypoid mass with inflammation and without suspicion for malignancy. Microscopic examination showed partly conventional, lowgrade dysplastic crypts forming a villous and rather complex structure. Ectopic crypt foci, slit-like serration pattern and serrated dysplasia with eosinophylic cytoplasm and centrally located nuclei were seen throughout the lesion, thus a traditional serrated adenoma (TSA) of the gallbladder was diagnosed. TSA represents the rarest subtype of serrated lesions in the colon and extracolonic manifestations are sporadically reported. Until now only a single case of a serrated adenoma was reported from the gallbladder. Here we describe the detailed clinical, pathological and molecular findings of our case and discuss these in the light of current literature data regarding this field.
C1 [Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Jakab, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Lehoczki, Csaba] Bajcsy Hospital, Department of SurgeryBudapest, Hungary.
[Patai, V. Arpad] Semmelweis University, Interdisciplinary Gastroenterology Working GroupBudapest, Hungary.
RP Micsik, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM micsikt@gmail.com
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Terada T. Histopathologic Features and Frequency of Gall Bladder Lesions in Consecutive 540 Cholecystectomies. Int J Clin Exp Pathol, 2013, 6(1):91–6.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610133
EP 1610137
DI 10.3389/pore.2022.1610133
PG 5
ER
PT J
AU Niwa, A
Tomita, H
Watanabe, N
Kiriyama, Sh
Hara, A
Tanaka, T
AF Niwa, Ayumi
Tomita, Hiroyuki
Watanabe, Naoki
Kiriyama, Shunya
Hara, Akira
Tanaka, Takuji
TI Case Report: A Case of Gallbladder Carcinosarcoma With Osteoclast-like Multinucleated Giant Cells that Was Associated With RANK-RANKL Signaling
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; gallbladder; carcinosarcoma; osteoclast-like multinucleated giant cell; RANK-RANKL signaling
ID case report; gallbladder; carcinosarcoma; osteoclast-like multinucleated giant cell; RANK-RANKL signaling
AB Introduction: Gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells is known to be most uncommon form of gallbladder cancer. Owing to its rarity, the pathogenesis of gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells is largely unknown. Case Presentation: We present a case of carcinosarcoma with osteoclast-like multinucleated giant cells in the gallbladder. A 57-year-old woman visited our hospital due to jaundice. An examination revealed calculous cholecystitis and gallbladder carcinoma. After cholecystectomy, macroscopic examination disclosed one whitish mass and another distinct brown and pendulous mass in the body of the gallbladder. A pathological examination revealed that each mass had a different histological type: adenosquamous carcinoma and carcinosarcoma with osteoclast-like multinucleated giant cells. Immunohistochemistry revealed that these osteoclast-like multinucleated giant cells are CD68(+), CD163(−), and MIB-1(−). In addition, the osteoclast-like multinucleated giant cells showed the strong expression of RANK and sarcoma cells around the osteoclast-like multinucleated giant cells, were positive for RANKL. Furthermore, RUNX2 was positive for some sarcoma cells. The result indicated that osteoclastic and osteoblast-like differentiation occurred in our case. Conclusion: To our knowledge, this is the first case to show the interaction of RANKRANKL signaling in gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells.
C1 [Niwa, Ayumi] Gifu University, Graduate School of Medicine, Department of Tumor PathologyGifu, Japan.
[Tomita, Hiroyuki] Gifu University, Graduate School of Medicine, Department of Tumor PathologyGifu, Japan.
[Watanabe, Naoki] Gifu Municipal Hospital, Research Center of Diagnostic Pathology (RC-DiP), Department of Diagnostic Pathology (DDP)Gifu, Japan.
[Kiriyama, Shunya] Gifu Municipal Hospital, Department of SurgeryGifu, Japan.
[Hara, Akira] Gifu University, Graduate School of Medicine, Department of Tumor PathologyGifu, Japan.
[Tanaka, Takuji] Gifu Municipal Hospital, Research Center of Diagnostic Pathology (RC-DiP), Department of Diagnostic Pathology (DDP)Gifu, Japan.
RP Tomita, H (reprint author), Gifu University, Graduate School of Medicine, Department of Tumor Pathology, Gifu, Japan.
EM h_tomita@gifu-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610134
EP 1610140
DI 10.3389/pore.2022.1610134
PG 7
ER
PT J
AU Kiss, A
AF Kiss, L. Anna
TI Inflammation in Focus: The Beginning and the End
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE EMT; inflammatory cytokines; reactive oxygen species; receptor internalization; chronic inflammation
ID EMT; inflammatory cytokines; reactive oxygen species; receptor internalization; chronic inflammation
AB The inflammation is an important biological response induced by various harmful stimuli, like viruses, bacterial infections, toxins, toxic compounds, tissue injury. During inflammation inflammatory cytokines and reactive oxygen species are produced. Inflammatory cytokines act on various receptors present on the plasma membrane of target cells. To initiate signaling cascade, and activate transcription factors, receptors should be internalized and enter the early endosomes, where the members of the signaling cascade can meet. The further cytoplasmic fate of the receptor plays crucial role in the progression and the course of inflammation. Usually acute inflammation removes injurious stimuli and helps to regain the normal healthy status of the organism. In contrast to this the uncontrolled chronic inflammation—stimulating other than immune cells, inducing transdifferentiation—can provide base of various serious diseases. This paper draws the attention of the long-lasting consequence of chronic inflammation, pointing out that one of the most important step in medication is to identify in time the factors initiating and maintaining inflammation.
C1 [Kiss, L. Anna] Semmelweis University, 1st Department of AnatomyBudapest, Hungary.
RP Kiss, A (reprint author), Semmelweis University, 1st Department of Anatomy, Budapest, Hungary.
EM kiss.anna@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610136
EP 1610142
DI 10.3389/pore.2021.1610136
PG 7
ER
PT J
AU Yang, Ch
Chen, K
AF Yang, Chenbo
Chen, Kuisheng
TI Long Non-Coding RNA in Esophageal Cancer: A Review of Research Progress
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE biomarkers; long non-coding RNA; molecular mechanism; esophageal cancer (EC); genomics
ID biomarkers; long non-coding RNA; molecular mechanism; esophageal cancer (EC); genomics
AB In recent years, there has been significant progress in the diagnosis and treatment of esophageal cancer. However, owing to the lack of early diagnosis strategies and treatment targets, the prognosis of patients with esophageal cancer remains unsatisfactory. There is an urgent need to identify novel biomarkers and treatment targets for esophageal cancer. With the development of genomics, long-chain non-coding RNAs (LncRNAs), which were once considered transcriptional “noise,” are being identified and characterized rapidly in large numbers. Recent research shows that LncRNAs are closely related to a series of steps in tumor development and play an important regulatory role in DNA replication, transcription, and post-transcriptional regulation. The abnormal expression of LncRNAs leads to tumor cell proliferation, migration, invasion, and treatment resistance. This review focuses on the latest progress in research on the abnormal expression and functional mechanisms of LncRNAs in esophageal cancer. Further, it discusses the potential applications of these findings towards achieving an early diagnosis, improving treatment efficacy, and evaluating the prognosis of esophageal cancer.
C1 [Yang, Chenbo] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Chen, Kuisheng] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
RP Chen, K (reprint author), The First Affiliated Hospital of Zhengzhou University, Department of Pathology, Zhengzhou, China.
EM chenksh2002@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610140
EP 1610152
DI 10.3389/pore.2022.1610140
PG 13
ER
PT J
AU Song, J
Yin, H
Zhu, Y
Fei, Sh
AF Song, Jiawei
Yin, Huanhuan
Zhu, Yong
Fei, Shengqi
TI Identification of Predictive Factors for Lymph Node Metastasis in pT1 Stage Colorectal Cancer Patients: A Retrospective Analysis Based on the Population Database
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; lymph node metastasis; SEER; predictive factors; pT1 stage
ID colorectal cancer; lymph node metastasis; SEER; predictive factors; pT1 stage
AB Objective: The purpose of this study was to identify predictive factors for lymph node metastasis (LNM) in pT1 stage colorectal cancer (CRC) patients. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 2,697 consecutive pT1 stage patients who underwent surgical resection were retrospectively reviewed. Predictive factors for LNM were identified by the univariate and multivariate logistic regression analysis. The Kaplan-Meier curves and multivariate Cox regression analysis were used to evaluate the relationships between LNM and overall survival (OS) as well as cancer specific survival (CSS) of pT1 stage CRC patients. Results: The prevalence of LNM in pT1 stage CRC patients was 15.2% (410/2,697). Patient age <60 years (OR:1.869, 95% CI: 1.505–2.321, p < 0.001), poorly differentiated or mucinous or signet ring cell adenocarcinoma (OR:2.075, 95% CI: 1.584–2.717, p < 0.001), elevated carcinoembryonic antigen (CEA) level (OR:1.343, 95% CI: 1.022–1.763, p = 0.033) and perineural invasion (PNI) (OR:6.212, 95% CI: 3.502–11.017, p < 0.001) were significantly associated with LNM in pT1 stage patients. The survival analysis demonstrated that pT1 stage patients with LNM had a worse OS (5-year OS: 82.2% vs 88.7%, p = 0.020) and CSS (5-year CSS: 74.9% vs 81.5%, p = 0.041) than those without lymph node metastasis. Lymph node metastasis was an independent predictor of poor OS (HR: 1.543, 95% CI: 1.156–2.060, p = 0.003) and CSS (HR: 1.614, 95% CI: 1.121–2.324, p = 0.010) for pT1 stage colorectal cancer patients. Conclusion: Age, differentiation type, CEA level and perineural invasion were independent predictive factors for LNM in pT1 stage CRC patients. These findings might provide further risk stratification for pT1 stage patients and help clinicians identify high-risk individuals.
C1 [Song, Jiawei] Changxing People’s Hospital, Department of Gastrointestinal SurgeryChangxing, China.
[Yin, Huanhuan] Changxing People’s Hospital, Department of GastroenterologyChangxing, China.
[Zhu, Yong] Changxing People’s Hospital, Department of Gastrointestinal SurgeryChangxing, China.
[Fei, Shengqi] Changxing People’s Hospital, Department of Gastrointestinal SurgeryChangxing, China.
RP Zhu, Y (reprint author), Changxing People’s Hospital, Department of Gastrointestinal Surgery, Changxing, China.
EM zy785184535@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610191
EP 1610198
DI 10.3389/pore.2022.1610191
PG 8
ER
PT J
AU Wang, A
Yuan, Y
Chu, H
Gao, Y
Jin, Z
Jia, Q
Zhu, B
AF Wang, Aoyun
Yuan, Yixiao
Chu, Han
Gao, Yixing
Jin, Zheng
Jia, Qingzhu
Zhu, Bo
TI Somatostatin Receptor 2: A Potential Predictive Biomarker for Immune Checkpoint Inhibitor Treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bioinformatics; tumor microenvironment; immune checkpoint inhibitors; somatostatin receptor 2; predictive biomarker
ID bioinformatics; tumor microenvironment; immune checkpoint inhibitors; somatostatin receptor 2; predictive biomarker
AB Somatostatin receptor 2 (SSTR2), the most abundant receptor of somatostatin (SST), possesses immunoreactivity and is altered in many cancers. However, the association between SSTR2 and efficacy of immune checkpoint inhibitors (ICIs) has not yet been reported. Immunohistochemistry (IHC) information across 20 cancers was collected from the Human Protein Atlas (HPA) and used to analyze the expression of SSTR2. Immune signatures collected from public databases, such as BioCarta or Reactome, were used to investigate the association between SSTR2 and the tumor microenviroment in the Cancer Genome Atlas (TCGA). Data from cohorts treated with ICIs were collected to assess whether SSTR2 is associated with benefits from ICIs treatment. In the HPA, we found the SSTR2 IHC-positive rate of 13 cancers to be above 50%. Five types of cancer express SSTR2 mildly (positive rate: 25%–50%), while the remaining two types of cancer barely stained SSTR2-positive (positive rate: 0%–24%). In TCGA analysis, immune cell signatures and immune function pathways were enriched in high SSTR2 expression groups in most cancers. In each ICIs treated cohort, patients with high SSTR2 expression experienced numerically superior objective response rate (Braun: 14.8% vs 13.4%, p = 0.85; Gide: 69.4% vs 40.5%, p = 0.025; Mariathasan: 22.4% vs 16.7%, p = 0.233; Miao: 37.5% vs 11.8%; Riaz: 32.0% vs 7.7%, p = 0.067) and overall survival (Braun: HR (95%CI): 0.80 [0.62–1.04], p = 0.80; Gide: HR (95%CI): 0.61 [0.29–1.30], p = 0.20; Mariathasan: HR (95%CI): 0.83 [0.64–1.08], p = 0.16; Miao: HR (95%CI): 0.24 [0.086–0.65], p = 0.0028; Nathanson cohort: HR (95%CI): 0 [0-inf], p = 0.18; Riaz: HR (95%CI): 0.24 [0.086–0.65], p = 0.028) than patients with low SSTR2 expression. In pooled cohort, we found these differences were significant (Pool: 24.6% vs 16.7%, p = 0.0077; HR (95% CI): 0.77 [0.65–0.91], p = 0.0018). Our results suggest that SSTR2 is a potential predictive biomarker for response to ICIs.
C1 [Wang, Aoyun] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
[Yuan, Yixiao] The Third Affiliated Hospital of Kunming Medical University, Department of Thoracic SurgeryKunming, China.
[Chu, Han] Sichuan University, College of Life Sciences, Key Laboratory of Bio-Resources and Eco-Environment, Center of Growth, Metabolism and AgingChengdu, China.
[Gao, Yixing] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
[Jin, Zheng] GloriousMed Clinical Laboratory (Shanghai) Co., Ltd., Research InstituteShanghai, China.
[Jia, Qingzhu] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
[Zhu, Bo] Third Military Medical University, Xinqiao Hospital, Institute of CancerChongqing, China.
RP Jia, Q (reprint author), Third Military Medical University, Xinqiao Hospital, Institute of Cancer, Chongqing, China.
EM jiaqingzhu0801@outlook.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610196
EP 1610205
DI 10.3389/pore.2022.1610196
PG 10
ER
PT J
AU Uchida, Sh
Kojima, T
Sugino, T
AF Uchida, Shiro
Kojima, Takaaki
Sugino, Takashi
TI Frequency and Clinicopathological Characteristics of Patients With KRAS/BRAF Double-Mutant Colorectal Cancer: An In Silico Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; KRAS; BRAF; bioinformatic analysis; colon; double mutation
ID cancer; KRAS; BRAF; bioinformatic analysis; colon; double mutation
AB KRAS and BRAF mutations are currently thought to be mutually exclusive as their cooccurrence is extremely rare. Therefore, clinicopathological and molecular characteristics of colorectal carcinoma with KRAS/BRAF double mutations are unclear. We aimed to investigate the frequency and clinicopathological characteristics of double-mutant colorectal carcinoma and its differences from KRAS/BRAF single-mutant colorectal carcinoma using bioinformatics tools. We estimated the KRAS/BRAF double mutation frequency in the whole exon and coding sequences via bioinformatic analyses of three datasets from cBioPortal. We compared the clinicopathological characteristics, microsatellite instability status, BRAF classification, and tumor mutation burden of patients harboring the double mutants with those of patients harboring KRAS or BRAF single mutations. We integrated three large datasets and found that the frequency of the KRAS/BRAF double mutation in the dataset was 1.2% (29/2347). The double mutation occurred more frequently in males, with a slightly higher occurrence in the right side of the colon. Sex, histological type, histological grade, microsatellite instability, and tumor mutation burden of the patients harboring KRAS-mutant, BRAF-mutant, and doublemutant colorectal carcinoma varied significantly. The frequency of double-mutant colorectal carcinoma was 60 times higher than that previously reported. Significantly fewer double-mutant colorectal carcinoma cases were classified as BRAF class 1 and more were classified as unknown. Our findings indicate that the biological characteristics of double-mutant tumors are different from those of single-mutant tumors.
C1 [Uchida, Shiro] Kikuna Memorial Hospital, Division of Diagnostic PathologyYokohama, Japan.
[Kojima, Takaaki] Nagoya University, Graduate School of Bioagricultural SciencesNagoya, Japan.
[Sugino, Takashi] Shizuoka Cancer Center, Division of PathologyShizuoka, Japan.
RP Uchida, Sh (reprint author), Kikuna Memorial Hospital, Division of Diagnostic Pathology, Yokohama, Japan.
EM Dr.Uchida@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610206
EP 1610214
DI 10.3389/pore.2022.1610206
PG 9
ER
PT J
AU Szekely, T
Krenacs, T
Maros, EM
Bodor, Cs
Daubner, V
Csizmadia, A
Vrabely, B
Timar, B
AF Szekely, Tamas
Krenacs, Tibor
Maros, Elod Mate
Bodor, Csaba
Daubner, Viktoria
Csizmadia, Annamaria
Vrabely, Brigitta
Timar, Botond
TI Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE primarymyelofibrosis progression; -stromal cell activation; -L-NGFR/CD271; -CXCL12; -phospho-ERK1- 2; -connexin 43 channels
ID primarymyelofibrosis progression; -stromal cell activation; -L-NGFR/CD271; -CXCL12; -phospho-ERK1- 2; -connexin 43 channels
AB In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result(s) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori’s silver impregnation. Here, we tested whether the expression growth related biomarkers L-NGFR/CD271, phospho-ERK1-2 and CXCL12 can be linked to the functional activation of bone marrow stromal cells during primary myelofibrosis progression. Immunoscores for all tested biomarkers showed varying strength of positive statistical correlation with the silver impregnation based myelofibrosis grades. The intimate relationship between spindle shaped stromal cells positive for all three markers and aberrant megakaryocytes was likely to reflect their functional cooperation. L-NGFR reaction was restricted to bone marrow stromal cells and revealed the whole length of their processes. Also, L-NGFR positive cells showed themost intersections, the best statistical correlations with myelofibrosis grades and the strongest interrater agreements. CXCL12 reaction highlighted stromal cell bodies and a weak extracellular staining in line with its constitutive release. Phospho-ERK1-2 reaction showed a similar pattern to CXCL12 in stromal cells with an additional nuclear staining in agreement with its role as a transcription factor. Both p-ERK1-2 and CXCL12 were also expressed at a moderate level in sinus endothelial cells. Connexin 43 gap junction communication channels, known to be required for CXCL12 release to maintain stem cell niche, were also expressed progressively in the myelofibrotic stromal network as a support of compartmental functions. Our results suggest that, diverse growth related pathways are activated in the functionally coupled bone marrow stromal cells during myelofibrosis progression. L-NGFR expression can be a useful biological marker of stromal cell activation which deserves diagnostic consideration for complementing Gomori’s silver impregnation.
C1 [Szekely, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Maros, Elod Mate] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Daubner, Viktoria] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csizmadia, Annamaria] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Vrabely, Brigitta] Peterfy Hospital - National Institute of Traumatology, Department of PathologyBudapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Krenacs, T (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM krenacs.tibor@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610217
EP 1610228
DI 10.3389/pore.2022.1610217
PG 12
ER
PT J
AU Mohas, A
Krencz, I
Varadi, Zs
Arato, G
Felkai, L
Kiss, JD
Moldvai, D
Sebestyen, A
Csoka, M
AF Mohas, Anna
Krencz, Ildiko
Varadi, Zsofia
Arato, Gabriella
Felkai, Luca
Kiss, Judit Dorottya
Moldvai, Dorottya
Sebestyen, Anna
Csoka, Monika
TI In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE osteosarcoma; mTOR; pathways; metabolic; metabolic adaptation; pediatric
ID osteosarcoma; mTOR; pathways; metabolic; metabolic adaptation; pediatric
AB Activation of the mTOR pathway has been observed in osteosarcoma, however the inhibition of mammalian target of rapamycin (mTOR) complex 1 has had limited results in osteosarcoma treatment. Certain metabolic pathways can be altered by mTOR activation, which can affect survival. Our aim was to characterize the mTOR profile and certain metabolic alterations in pediatric osteosarcoma to determine the interactions between the mTOR pathway and metabolic pathways. We performed immunohistochemistry on 28 samples to analyze the expression of mTOR complexes such as phospho-mTOR (pmTOR), phosphorylated ribosomal S6 (pS6), and rapamycin-insensitive companion of mTOR (rictor). To characterize metabolic pathway markers, we investigated the expression of phosphofructokinase (PFK), lactate dehydrogenase-A (LDHA), β-F1- ATPase (ATPB), glucose-6-phosphate dehydrogenase (G6PDH), glutaminase (GLS), fatty acid synthetase (FASN), and carnitin-O-palmitoyltransferase-1 (CPT1A). In total, 61% of the cases showed low mTOR activity, but higher pmTOR expression was associated with poor histological response to chemotherapy and osteoblastic subtype. Rictor expression was higher in metastatic disease and older age at the time of diagnosis. Our findings suggest the importance of the Warburg-effect, pentose-phosphate pathway, glutamine demand, and fatty-acid beta oxidation in osteosarcoma cells. mTOR activation is linked to several metabolic pathways. We suggest performing a detailed investigation of the mTOR profile before considering mTORC1 inhibitor therapy. Our findings highlight that targeting certain metabolic pathways could be an alternative therapeutic approach.
C1 [Mohas, Anna] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Varadi, Zsofia] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Arato, Gabriella] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Felkai, Luca] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kiss, Judit Dorottya] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Moldvai, Dorottya] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Mohas, A (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM mohas.anna@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610231
EP 1610241
DI 10.3389/pore.2022.1610231
PG 11
ER
PT J
AU Mohamed, F
Kurdi, M
Baeesa, S
Sabbagh, JA
Hakamy, S
Maghrabi, Y
Alshedokhi, M
Dallol, A
Halawa, T
Najjar, A
Fdl-Elmula, I
AF Mohamed, Fawaz
Kurdi, Maher
Baeesa, Saleh
Sabbagh, Jafar Abdulrahman
Hakamy, Sahar
Maghrabi, Yazid
Alshedokhi, Mohammed
Dallol, Ashraf
Halawa, F. Taher
Najjar, A. Ahmed
Fdl-Elmula, Imad
TI The Diagnostic Value of Pan-Trk Expression to Detect Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion in CNS Tumours: A Study Using Next-Generation Sequencing Platform
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; next-generation sequencing; CNS tumours; NTRK-fusions; Pan-Trk; TruSight Oncology500
ID immunohistochemistry; next-generation sequencing; CNS tumours; NTRK-fusions; Pan-Trk; TruSight Oncology500
AB Background: Neurotrophic tyrosine receptor kinase (NTRK) fusion has been detected in rare types of CNS tumours, which can promote tumorigenesis. The efficacy of Trk inhibitor became a significant therapeutic interest. Our aim was to investigate whether Pan-Trk immunohistochemistry (IHC) is a reliable and efficient marker for detecting NTRK-fusion in different brain tumours. Methods: This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) has been performed on all FFPE tissues. Parallelly, NTRK-rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform. Results: The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDHwildtype glioblastomas, four IDHmutant grade four astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; seven cases were in the paediatric age group, and 16 were adult. Pan- Trk expression was detected in 11 (47.8%) tumours, and 12 (52.1%) tumours showed no Pan-Trk expression. Nine Cases (82%) with different Pan-Trk expressions did not reveal NTRK-rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have NTRK2-fusions (SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2). All the 12 cases (100%) with no Pan-Trk expression have shown no NTRK-fusions. There was no statistically significant association between Pan-Trk expression and NTRK-fusion (p = 0.217). The detection of NTRK- fusions using NGS had high specificity over NTRK-fusion detection by using Pan-Trk IHC. Conclusion: Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for NTRKfusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.
C1 [Mohamed, Fawaz] King Abdulaziz University, Faculty of Medicine, Department of PathologyRabigh, Saudi Arabia.
[Kurdi, Maher] King Abdulaziz University, Faculty of Medicine, Department of PathologyRabigh, Saudi Arabia.
[Baeesa, Saleh] King Abdulaziz University, Faculty of Medicine in Rabigh, Division of NeurosurgeryJeddah, Saudi Arabia.
[Sabbagh, Jafar Abdulrahman] King Abdulaziz University, Faculty of Medicine in Rabigh, Division of NeurosurgeryJeddah, Saudi Arabia.
[Hakamy, Sahar] King Abdulaziz University, Neuromuscular and Brain Tumour UnitJeddah, Saudi Arabia.
[Maghrabi, Yazid] King Faisal Specialist Hospital, Department of NeuroscienceJeddah, Saudi Arabia.
[Alshedokhi, Mohammed] King Abdulaziz University, Center of Excellence in Genomic Medicine ResearchJeddah, Saudi Arabia.
[Dallol, Ashraf] King Abdulaziz University, Center of Excellence in Genomic Medicine ResearchJeddah, Saudi Arabia.
[Halawa, F. Taher] King Abdulaziz University, Faculty of Medicine, Department of PediatricsRabigh, Saudi Arabia.
[Najjar, A. Ahmed] Taibah University, College of MedicineAlmadinah Almunawwarah, Saudi Arabia.
[Fdl-Elmula, Imad] Al-Neelain University, Faculty of Medicine, Department of Clinical GeneticsKhartoum, Sudan.
RP Kurdi, M (reprint author), King Abdulaziz University, Faculty of Medicine, Department of Pathology, Rabigh, Saudi Arabia.
EM Ahkurdi@kau.edu.sa
CR Solomon JP, Benayed R, Hechtman JF, Ladanyi M. Identifying Patients with NTRK Fusion Cancer. Ann Oncol, 2019, 30:viii16–viii22. Epub 2019 Dec 24., DOI 10.1093/annonc/mdz384
Torre M, Vasudevaraja V, Serrano J, DeLorenzo M, Malinowski S, Blandin A-F, et al. Molecular and Clinicopathologic Features of Gliomas Harboring NTRK Fusions. Acta Neuropathol Commun, 2020, 8:107., DOI 10.1186/s40478- 020-00980-z
Amatu A, Sartore-Bianchi A, Siena S. NTRK Gene Fusions as Novel Targets of Cancer Therapy across Multiple Tumour Types. ESMO Open, 2016, 1: e000023., DOI 10.1136/esmoopen-2015-000023
Lange A, Lo H-W. Inhibiting TRK Proteins in Clinical Cancer Therapy. Cancers, 2018, 10:105., DOI 10.3390/cancers10040105
Vaishnavi A, Le AT, Doebele RC. TRKing Down an OldOncogene in a new era of Targeted Therapy. Cancer Discov, 2015, 5:25–34., DOI 10.1158/2159-8290. cd-14-0765
Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D, et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol, 2017, 41:1547–51., DOI 10.1097/ pas.0000000000000911
Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, et al. NTRK Fusion Detection across Multiple Assays and 33,997 Cases: Diagnostic Implications and Pitfalls. Mod Pathol, 2020, 33:38–46., DOI 10.1038/s41379- 019-0324-7
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a Summary. Neuro Oncol, 2021, 23:1231–51., DOI 10.1093/neuonc/noab106
Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, et al. EANO Guidelines on the Diagnosis and Treatment of Diffuse Gliomas of Adulthood. Nat Rev Clin Oncol, 2021, 18:170–86., DOI 10.1038/s41571-020- 00447-z
Kurdi M, Alghamdi B, Butt NS, Baeesa S. The Relationship between CD204 M2-Polarized Tumour-Associated Macrophages, TAMs), Tumour- Infiltrating Lymphocytes, TILs), and Microglial Activation in Glioblastoma Microenvironment: a Novel Immune Checkpoint Receptor Target. Discov Onc, 2021, 12:28., DOI 10.1007/s12672-021-00423-8
Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Childrenficacy of Larotrectinib in TRK Fusionepositive Cancers in Adults and Children. N Engl J Med, 2018, 378:731–9., DOI 10.1056/NEJMoa1714448
Bourhis A, Caumont C, Quintin-Roue I, Magro E, Dissaux G, Detection of NTRK Fusions in Glioblastoma: Fluorescent In Situ Hybridisation Is More Useful Than Pan-TRK Immunohistochemistry as a Screening Tool Prior to RNA Sequencing, A Remoue, et al. Detection of NTRK Fusions in Glioblastoma: Fluorescent In Situ Hybridisation Is More Useful Than Pan- TRK Immunohistochemistry as a Screening Tool Prior to RNA Sequencing. Pathology, 2021, S0031-3025(21):00429–3., DOI 10.1016/j.pathol.2021.05.100
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610233
EP 1610242
DI 10.3389/pore.2022.1610233
PG 10
ER
PT J
AU Nozzoli, F
Lazar, A
Castiglione, F
Campanacci, AD
Beltrami, G
De Logu, F
Caporalini, Ch
Massi, D
Roviello, G
AF Nozzoli, Filippo
Lazar, J. Alexander
Castiglione, Francesca
Campanacci, Andrea Domenico
Beltrami, Giovanni
De Logu, Francesco
Caporalini, Chiara
Massi, Daniela
Roviello, Giandomenico
TI NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Pan-Trk; NTRK; ETV6-NTRK3; NTRK-rearranged tumors; paediatric sarcomas
ID Pan-Trk; NTRK; ETV6-NTRK3; NTRK-rearranged tumors; paediatric sarcomas
AB Undifferentiated round cell sarcomas (URCS) of soft tissue and bone and tumours of uncertain differentiation (TUD) are commonly ascribed to a subset of neoplasms with low frequency of NTRK gene fusions. However, more recently NTRK-rearranged round and spindle cell tumours have been noted in case reports and in limited or heterogeneous cohorts. The aim of our study was to investigate the presence of NTRK gene fusions in a large retrospective cohort of paediatric URCS and TUD after a systematic review of the diagnosis, according to the recently updated WHO classification scheme. One-hundred and five patients with diagnosis of URCS or TUD, involving the bone or soft tissue, were retrospectively evaluated. After the case selection and the histopathological review of the case cohort, pan-Trk immunohistochemistry (IHC) testing was performed on formalin-fixed paraffinembedded (FFPE) tissues. Tumour RNA was extracted from FFPE tissue and subjected to next-generation sequencing (NGS) library preparation, using a 10-gene NGS fusion panel, sequenced on an Illumina MiSeq. The NGS-positive cases were further confirmed by real-time PCR. On immunohistochemical screening, 12/105 (11.4%) caseswere positive using the pan- Trk antibody, showing three different staining patterns with the cytoplasmic distribution being most common. Molecular analysis using NGS and confirmed by the real-rime PCR detected two positive cases for the ETV6-NTRK3 fusion. The histological pattern of the two positive cases, together with the demonstration of the NTRK rearrangement, leaded to re-classify these previously not otherwise specified sarcomas with uncertain differentiation into the emerging category of NTRK-rearranged neoplasms. In addition, we found the two NTRK fused neoplasms showing a clinical indolent course, in contrast with literature.
C1 [Nozzoli, Filippo] University of Florence, Department of Health Sciences, Section of Anatomic PathologyFlorence, Italy.
[Lazar, J. Alexander] The University of Texas, M.D. Anderson Cancer Center, Departments of Pathology and Genomic MedicineHouston, TX, USA.
[Castiglione, Francesca] University of Florence, Department of Health Sciences, Section of Anatomic PathologyFlorence, Italy.
[Campanacci, Andrea Domenico] Careggi University Hospital, Department of Orthopaedic Oncology and Reconstructive SurgeryFlorence, Italy.
[Beltrami, Giovanni] Meyer Children’s Hospital, Department of Paediatric Orthopaedic OncologyFlorence, Italy.
[De Logu, Francesco] University of Florence, Department of Health Sciences, Clinical Pharmacology and Oncology UnitFlorence, Italy.
[Caporalini, Chiara] University of Florence, Meyer Children’s Hospital, Pathology UnitFlorence, Italy.
[Massi, Daniela] University of Florence, Department of Health Sciences, Section of Anatomic PathologyFlorence, Italy.
[Roviello, Giandomenico] University of Florence, Department of Health Sciences, Medical OncologyFlorence, Italy.
RP Nozzoli, F (reprint author), University of Florence, Department of Health Sciences, Section of Anatomic Pathology, Florence, Italy.
EM filippo.nozzoli@unifi.it
CR Sbaraglia M, Bellan E, Dei Tos AP. The 2020WHOClassification of Soft Tissue Tumours: News and Perspectives. Pathologica, 2020, 113:70–84., DOI 10.32074/ 1591-951X-213
Albert CM, Davis JL, Federman N, Casanova M, Laetsch TW. TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening. Jco, 2019, 37(6):513–24., DOI 10.1200/JCO.18.00573
Wong DD, Vargas AC, Bonar F, Maclean F, Kattampallil J, Stewart C, et al. NTRK-rearranged Mesenchymal Tumours: Diagnostic Challenges, Morphological Patterns and Proposed Testing Algorithm. Pathology, 2020, 52(4):401–9., DOI 10.1016/j.pathol.2020.02.004
Vargas AC, Ardakani NM, Wong DD, Maclean FM, Kattampallil J, Boyle R, et al. Chromosomal Imbalances Detected in NTRK -rearranged Sarcomas by the Use of Comparative Genomic Hybridisation. Histopathology, 2020, 78(7): 932–42., DOI 10.1111/his.14295
Kao Y-C, Sung Y-S, Argani P, Swanson D, Alaggio R, Tap W, et al. NTRK3 Overexpression in Undifferentiated Sarcomas with YWHAE and BCOR Genetic Alterations. Mod Pathol, 2020, 33(7):1341–9., DOI 10.1038/s41379- 020-0495-2
Solomon JP, Linkov I, Rosado A,Mullaney K, Rosen EY, Frosina D, et al. NTRK Fusion Detection across Multiple Assays and 33,997 Cases: Diagnostic Implications and Pitfalls. Mod Pathol, 2020, 33(1):38–46., DOI 10.1038/s41379-019-0324-7
Davis JL, Lockwood CM, Stohr B, Boecking C, Al-Ibraheemi A, DuBois SG, et al. Expanding the Spectrum of Pediatric NTRK-Rearranged Mesenchymal Tumors. Am J Surg Pathol, 2019, 43(4):435–45., DOI 10.1097/PAS. 0000000000001203
Marchio C, Scaltriti M, Ladanyi M, Iafrate AJ, Bibeau F, Dietel M, et al. ESMO Recommendations on the Standard Methods to Detect NTRK Fusions in Daily Practice and Clinical Research. Ann Oncol, 2019, 30(9):1417–27., DOI 10.1093/ annonc/mdz204
Enneking WF, Spanier SS, Goodman MA. A System for the Surgical Staging of Musculoskeletal Sarcoma. Clin Orthop Relat Res, 1980, 153(153):106–120. PMID: 7449206., DOI 10.1097/00003086-198011000-00013
Tanaka K, Ozaki T. New TNM Classification, AJCC Eighth Edition, of Bone and Soft Tissue Sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol, 2019, 49(2):103–7. PMID: 30423153., DOI 10.1093/jjco/hyy157
Picci P, Rougraff BT, Bacci G, Neff JR, Sangiorgi L, Cazzola A, et al. Prognostic Significance of Histopathologic Response to Chemotherapy in Nonmetastatic Ewing’s Sarcoma of the Extremities. Jco, 1993, 11(9):1763–9. PMID: 8355043., DOI 10.1200/JCO.1993.11.9.1763
Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO, et al. Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. Am J Surg Pathol, 2018, 42(7):927–35., DOI 10.1097/PAS.0000000000001062
Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib inTRKFusion-Positive Cancers in Adults and Children. N Engl J Med, 2018, 378(8):731–9., DOI 10.1056/NEJMoa1714448
Kheder ES, Hong DS. Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins. Clin Cancer Res, 2018, 24(23):5807–14., DOI 10.1158/1078- 0432.CCR-18-1156
Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, et al. Expression of the ETV6-NTRK3 Gene Fusion as a Primary Event in Human Secretory Breast Carcinoma. Cancer Cell, 2002, 2:367–76., DOI 10. 1016/s1535-6108(02)00180-0
Rubin BP, Chen C-J, Morgan TW, Xiao S, Grier HE, Kozakewich HP, et al. Congenital Mesoblastic Nephroma T(12;15, Is Associated withETV6-NTRK3 Gene Fusion. Am J Pathol, 1998, 153:1451–8., DOI 10.1016/S0002-9440(10)65732-X
Knezevich SR, McFadden DE, TaoW, Lim JF, Sorensen PHB. A Novel ETV6- NTRK3 Gene Fusion in Congenital Fibrosarcoma. Nat Genet, 1998, 18:184–7., DOI 10.1038/ng0298-184
Suurmeijer AJ, Dickson BC, Swanson D, Zhang L, Sung YS, Huang HY, et al. The Histologic Spectrum of Soft Tissue Spindle Cell Tumors with NTRK3 Gene Rearrangements. Genes Chromosomes Cancer, 2019, 58(11):739–46., DOI 10.1002/gcc.22767
Solomon JP, Hechtman JF. Detection of NTRK Fusions: Merits and Limitations of Current Diagnostic Platforms. Cancer Res, 2019, 79(13): 3163–8., DOI 10.1158/0008-5472.CAN-19-0372
Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D, et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol, 2017, 41(11):1547–51., DOI 10. 1097/PAS.0000000000000911
Murphy DA, Ely HA, Shoemaker R, Boomer A, Culver BP, Hoskins I, et al. Detecting Gene Rearrangements in Patient Populations through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing. Appl Immunohistochem Mol Morphol, 2017, 25(7):513–23., DOI 10.1097/PAI.0000000000000360
Chiang S, Cotzia P, Hyman DM, Drilon A, Tap WD, Zhang L, et al. NTRK Fusions Define a Novel Uterine Sarcoma Subtype with Features of Fibrosarcoma. Am J Surg Pathol, 2018, 42(6):791–8., DOI 10.1097/PAS. 0000000000001055
Hung YP, Fletcher CDM, Hornick JL. Evaluation of Pan-TRK Immunohistochemistry in Infantile Fibrosarcoma, Lipofibromatosis-like Neural Tumour and Histological Mimics. Histopathology, 2018, 73(4): 634–44., DOI 10.1111/his.13666
Penault-Llorca F, Rudzinski ER, Sepulveda AR. Testing Algorithm for Identification of Patients with TRK Fusion Cancer. J Clin Pathol, 2019, 72(7):460–7., DOI 10.1136/jclinpath-2018-205679
Siozopoulou V, Smits E, De Winne K, Marcq E, Pauwels P. NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects. Diagnostics, 2021, 11(3):478., DOI 10.3390/diagnostics11030478
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610237
EP 1610245
DI 10.3389/pore.2022.1610237
PG 9
ER
PT J
AU Yang, A
Li, M
Fang, M
AF Yang, Ai
Li, Min
Fang, Mingzhi
TI Corrigendum: The Research Progress of Direct KRAS G12C Mutation Inhibitors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE KRAS mutation; targeted drugs; oncogene; inhibitor; oncology
ID KRAS mutation; targeted drugs; oncogene; inhibitor; oncology
AB A Corrigendum on The Research Progress of Direct KRAS G12C Mutation Inhibitors by Yang, A., Li, M., and Fang, M. (2021). Pathol. Oncol. Res. 27:631095. doi: 10.3389/pore.2021. 631095 In the original article, there were mistakes in the legend for all of the figures as published. The source of the pictures cited in the article were not included. The correct legends appear below. The sources for the figures have been added to the reference list, and the reference numbering has been updated to accommodate this. The new references are appear below. The authors apologize for this error and state that authorization has been obtained from the author of each picture, and this does not change the scientific conclusions of the article in any way. The original article has been updated.
C1 [Yang, Ai] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
[Li, Min] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
[Fang, Mingzhi] Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of OncologyNanjing, China.
RP Li, M (reprint author), Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Department of Oncology, Nanjing, China.
EM doctorlimin@163.com
CR 3. Prior IA, Lewis PD, and Mattos C. A Comprehensive Survey of RasMutations in Cancer. Cancer Res, 2012, 72(10):2457–67., DOI 10.1158/0008-5472.can-11-2612 4. Simanshu DK, Nissley DV, and Mccormick F. RAS Proteins and Their Regulators in Human Disease. Cell, 2017, 170(1):17. 14. Huili L, Fei J, Jiwei R, Tao L, Yadong C. Research Advances on KRAS and Its Inhibitors. Acta Pharmaceutica Sinica, 2020, 44(1):43–55. 20. Xin L, Yijun W, and Pingyu L. Recent Advancement In Targeting The KRASG12C Mutant For Cancer Therapy. Acta Pharmaceutica Sinica, 2021, 56(2):374–82. 30. Fell JB, Fischer JP, Baer BR, Blake JF, Bouhana K, Briere DM, et al. Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer. JMed Chem, 2020, 63(13):6679–93., DOI 10.1021/ acs.jmedchem.9b02052 33. Tran TH, Alexander P, Dharmaiah S, Agamasu C, and Balius TE. The Small Molecule BI-2852 Induces A Nonfunctional Dimer Of KRAS Proc National Academy Sci., 2020, 117(7).
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610250
EP 1610254
DI 10.3389/pore.2021.1610250
PG 5
ER
PT J
AU Diao, B
Yang, P
AF Diao, Bowen
Yang, Ping
TI Corrigendum: Comprehensive Analysis of the Expression and Prognosis for Laminin Genes in Ovarian Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE ovarian cancer; metastasis; laminins; cancer prognosis; bioinformatical analysis
ID ovarian cancer; metastasis; laminins; cancer prognosis; bioinformatical analysis
AB A Corrigendum on Comprehensive Analysis of the Expression and Prognosis for Laminin Genes in Ovarian Cancer by Diao, B., Yang, P. (2021). Pathol. Oncol. Res. 27:1609855. doi: 10.3389/pore.2021.1609855 There is an error in the Funding statement. The correct number for National Natural Science Foundation of China is “82072893”. In the original article, there was an error. In the results section, the database name in the first paragraph was incorrect. A correction has been made to Results, Genetic Mutations in Laminins and Their Associations With Overall Survival and Disease-free Survival in Patients With Ovarian Cancer, paragraph one: “We evaluated genetic alterations in laminins and their relationships with the OS and DFS of OC patients registered in the cBioPortal database”. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
C1 [Diao, Bowen] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
[Yang, Ping] Shihezi University, School of Medicine, First Affiliated Hospital, Department of GynecologyShihezi, China.
RP Yang, P (reprint author), Shihezi University, School of Medicine, First Affiliated Hospital, Department of Gynecology, Shihezi, China.
EM pingy2018@163.com
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610258
EP 1610258
DI 10.3389/pore.2022.1610258
PG 1
ER
PT J
AU Muller, J
Szucs-Farkas, D
Szegedi, I
Csoka, M
Garami, M
Tiszlavicz, GyL
Hauser, P
Krivan, G
Csanadi, K
Ottoffy, G
Nagy, B
Kiss, Cs
Kovacs, G
AF Muller, Judit
Szucs-Farkas, Dora
Szegedi, Istvan
Csoka, Monika
Garami, Miklos
Tiszlavicz, Gyorgyi Lilla
Hauser, Peter
Krivan, Gergely
Csanadi, Krisztina
Ottoffy, Gabor
Nagy, Bela
Kiss, Csongor
Kovacs, Gabor
TI Clinical Course of COVID-19 Disease in Children Treated With Neoplastic Diseases in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SARS-CoV-2; COVID-19; pediatric malignancy; chemotherapy delay; SARS-CoV-2S antibodies
ID SARS-CoV-2; COVID-19; pediatric malignancy; chemotherapy delay; SARS-CoV-2S antibodies
AB We report on children with cancer in Hungary suffering from COVID-19, surveying a 13- months-long period of time. We performed a retrospective clinical trial studying the medical documentation of children treated in seven centers of the Hungarian Pediatric Oncology- Hematology Group. About 10% of children admitted to tertiary hemato-oncological centers for anti-neoplastic treatment or diagnosis for de novo malignancies were positive for SARS-CoV-2 infection. Nearly two-thirds of the infected patients were asymptomatic or had only mild symptoms but showed seropositivity by 1–4.5 months after positive PCR. One third of the SARS-CoV-2-positive children were hospitalized due to symptomatic COVID-19. Five children required antiviral treatment with remdesivir. One child was referred to the intensive care unit, requiring intubation and mechanical ventilation. Delay in the scheduled anti-cancer treatment did not exceed 2 weeks in the majority (89%) of cases. There was only one patient requiring treatment deferral longer than a month. There was no COVID-19-related death in patients under 18 years of age, and nor was multisystem inflammatory syndrome diagnosed. In conclusion, SARS-CoV-2 infection did not represent an untoward risk factor among children with cancer in Hungary.
C1 [Muller, Judit] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szucs-Farkas, Dora] Medical and Health Science Center, University of Debrecen, Department of PediatricsDebrecen, Hungary.
[Szegedi, Istvan] Medical and Health Science Center, University of Debrecen, Department of PediatricsDebrecen, Hungary.
[Csoka, Monika] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Garami, Miklos] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tiszlavicz, Gyorgyi Lilla] University of Szeged, Department of PediatricsSzeged, Hungary.
[Hauser, Peter] Borsod-Abauj-Zemplen County Hospital, Child Health Centre, Haematology/ Oncology and Pediatric Bone Marrow Transplantation UnitMiskolc, Hungary.
[Krivan, Gergely] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Csanadi, Krisztina] Heim Pal Children’s Hospital, Hemato-Oncology UnitBudapest, Hungary.
[Ottoffy, Gabor] University of Pecs, Department of PediatricsPecs, Hungary.
[Nagy, Bela] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Kiss, Csongor] Medical and Health Science Center, University of Debrecen, Department of PediatricsDebrecen, Hungary.
[Kovacs, Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kiss, Cs (reprint author), Medical and Health Science Center, University of Debrecen, Department of Pediatrics, Debrecen, Hungary.
EM kisscs@med.unideb.hu
CR Pollard CA, Morran MP, Nestor-Kalinoski AL. The COVID-19 Pandemic: a Global Health Crisis. Physiol Genomics, 2020, 52(11):549–57., DOI 10.1152/ physiolgenomics.00089.2020
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Tezer H, Bedi_r Demi_rdag T. Novel Coronavirus Disease, COVID-19, in Children. Turk J Med Sci, 2020, 50(SI-1):592–603., DOI 10.3906/sag- 2004-174
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610261
EP 1610266
DI 10.3389/pore.2022.1610261
PG 6
ER
PT J
AU Chai, Y
Jiao, Sh
Peng, X
Gan, Q
Chen, L
Hu, X
Hao, L
Zhang, Sh
Tao, Q
AF Chai, Yong
Jiao, Shoufeng
Peng, Xin
Gan, Qiang
Chen, Leifeng
Hu, Xiaolu
Hao, Liang
Zhang, Shouhua
Tao, Qiang
TI RING-Finger Protein 6 promotes Drug Resistance in Retinoblastoma via JAK2/STAT3 Signaling Pathway
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; signaling pathway; drug resistance; retinoblastoma; RING-finger protein 6
ID biomarker; signaling pathway; drug resistance; retinoblastoma; RING-finger protein 6
AB Chemotherapy is the first-line treatment for human retinoblastoma (RB), but the occurrence of drug resistance greatly limited its efficacy in practice. RING-finger protein 6 (RNF6) is an E3 ubiquitin ligase that is aberrantly upregulated in a range of cancers and plays important roles in cancer progression. However, the role of RNF6 in RB is largely unknown. In this study, we investigated the role of RNF6 in RB drug resistance. Two carboplatin-resistant RB cells, Y-79/CR and SO-Rb50/CR, were generated based on Y-79 and SO-Rb50 cells. RT-PCR and western blot analyses showed that RNF6 expression on both mRNA and protein levels was significantly increased in Y-79/CR and SO-Rb50/CR cells comparing to their parental cells. Knockdown of RNF6 using siRNA in Y-79/CR and SO-Rb50/CR cells resulted in cells sensitive to carboplatin on a RNF6 siRNA dose dependent manner. Similarly, RNF6 overexpression in parental Y-79 and SORb50 cells could help cells gain resistance to carboplatin on a RNF6 expression dependent manner. Signaling pathway analyses revealed that JAK2/STAT3 pathway was involved in the RNF6-induced carboplatin resistance in RB cells. We further revealed that RNF6 expression in both Y-79 and SO-Rb50 cells could render cells resistant to multiple anticancer drugs including carboplatin, vincristine and etoposide, an implication of RNF6 as a biomarker for RB drug resistance. Taken together, our study has revealed that RNF6 is upregulated in drug-resistant RB cells and RNF6 promotes drug resistance through JAK2/ STAT3 signaling pathway. The importance of RNF6 in RB cells drug resistance may represent this protein as a potential biomarker and treatment target for drug resistance in RB.
C1 [Chai, Yong] The Affiliated Children’s Hospital of Nanchang University, Department of OphthalmologyNanchang, China.
[Jiao, Shoufeng] The First Affiliated Hospital of Nanchang University, Department of PharmacyNanchang, China.
[Peng, Xin] The Affiliated Children’s Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Gan, Qiang] The Affiliated Children’s Hospital of Nanchang University, Department of OphthalmologyNanchang, China.
[Chen, Leifeng] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Hu, Xiaolu] The Affiliated Children’s Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Hao, Liang] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Zhang, Shouhua] The Affiliated Children’s Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Tao, Qiang] The Affiliated Children’s Hospital of Nanchang University, Department of General SurgeryNanchang, China.
RP Zhang, Sh (reprint author), The Affiliated Children’s Hospital of Nanchang University, Department of General Surgery, Nanchang, China.
EM zshouhua416@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610273
EP 1610281
DI 10.3389/pore.2022.1610273
PG 9
ER
PT J
AU Szita, RV
Mikala, G
Kozma, A
Fabian, J
Hardi, A
Alizadeh, H
Rajnics, P
Rejto, L
Szendrei, T
Varoczy, L
Nagy, Zs
Illes,
Valyi-Nagy, I
Masszi, T
Varga, G
AF Szita, Reka Virag
Mikala, Gabor
Kozma, Andras
Fabian, Janos
Hardi, Apor
Alizadeh, Hussain
Rajnics, Peter
Rejto, Laszlo
Szendrei, Tamas
Varoczy, Laszlo
Nagy, Zsolt
Illes, Arpad
Valyi-Nagy, Istvan
Masszi, Tamas
Varga, Gergely
TI Targeted Venetoclax Therapy in t(11; 14) Multiple Myeloma: Real World Data From Seven Hungarian Centers
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; venetoclax; t(11; 14); relapsed/refractory; plasma cell leukemia; amyloidosis
ID multiple myeloma; venetoclax; t(11; 14); relapsed/refractory; plasma cell leukemia; amyloidosis
AB Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, had shown promising results in patients with translocation t(11;14), but questions remain open about its optimal use. We have contacted all Hungarian haematology centers for their experience treating t(11;14) myeloma patients with venetoclax. 58 patients were reported. 37 received venetoclax in the relapsed/ refractory setting with few or no other therapeutic options available. 21 patients started venetoclax as salvage after failing to achieve satisfactory response to first line therapy. In the relapsed/refractory setting objective response rate (ORR) was 94%, median progression-free survival (PFS) 10.0 months and median overall survival (OS) 14.6 months. In reinduction patients, ORR was 100%, median PFS and OS were not reached. Importantly, we found no adverse effect of high risk features such as deletion 17p or renal failure, in fact renal failure ameliorated in 42% of the cases, including three patients who became dialysis independent. Our study also reports the highest number of plasma cell leukemia cases successfully treated with venetoclax published in literature, with refractory plasma cell leukemia patients achieving a median PFS of 10.0 and a median OS of 12.2 months.
C1 [Szita, Reka Virag] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Kozma, Andras] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai LaboratoriumBudapest, Hungary.
[Fabian, Janos] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Hardi, Apor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Alizadeh, Hussain] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Rajnics, Peter] Kaposi Mor Teaching Hospital, Department of HematologyKaposvar, Hungary.
[Rejto, Laszlo] Josa Andras County HospitalNyiregyhaza, Hungary.
[Szendrei, Tamas] Vas County Markusovszky HospitalSzombathely, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Nagy, Zsolt] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Valyi-Nagy, Istvan] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Masszi, Tamas] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Varga, Gergely] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
RP Varga, G (reprint author), Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary.
EM vargager@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610276
EP 1610284
DI 10.3389/pore.2022.1610276
PG 9
ER
PT J
AU Jiang, Y
Zhang, Z
Wang, X
Feng, Z
Hong, B
Yu, D
Wang, Y
AF Jiang, Yu
Zhang, Zhiqiang
Wang, Xian
Feng, Zhenzhong
Hong, Bo
Yu, Dexin
Wang, Yi
TI A Novel Prognostic Factor TIPE2 in Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epithelial-mesenchymal transition; bladder cancer; TIPE2; cystectomy; urothelial carcinoma
ID epithelial-mesenchymal transition; bladder cancer; TIPE2; cystectomy; urothelial carcinoma
AB Objective: We sought to identify tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2/TNFAIP8L2) expression in bladder cancer and its relationship to clinicopathological findings and prognosis. Methods: Immunohistochemical (IHC) staining for TIPE2 was performed on 110 archived radical cystectomy specimens. Ten high-power fields were randomly selected from each specimen to observe and record the percentage of immunoreactive cells of TIPE2 in tumor cells (grade 0–4) and the corresponding immunostaining intensity (grade 0–3). The expression score of TIPE2 was obtained by multiplying the results of the above two scores, which ranged from 0 to 12 points. The cut-off point of the sum of the scores were defined as follows: 0–3 scores were defined as negative expression (-); >3 scores were classified as positive expression, < 7, low expression, ≥7, high expression. Results: In 110 cases, TIPE2 was stained in various degrees in bladder cancer tissues, and expressed in both nucleus and cytoplasm. 4.5% (5/110) showed negative expression, 40.9% (45/110) showed low expression, and 54.5% (60/110) showed high expression. TIPE2 expression was negatively correlated with lymph node metastasis (p = 0.004) and disease progression (p = 0.021). Survival curves were plotted to show that patients with high TIPE2 expression had a progression-free survival curve above those with negative/ low TIPE2 expression (p = 0.027). In multivariate Cox proportional hazard regression analysis, TIPE2 was a protective factor for progression-free survival in bladder urothelial carcinoma (p = 0.031), pT stage (p = 0.016) was a risk factor for progression-free survival, and age was a risk factor for overall survival (p = 0.020). Conclusion: TIPE2 may be a new biomarker to predict the disease progression and prognosis of patients with urothelial carcinoma of the bladder.
C1 [Jiang, Yu] Second Affiliated Hospital of Anhui Medical University, Department of UrologyHefei, China.
[Zhang, Zhiqiang] Second Affiliated Hospital of Anhui Medical University, Department of UrologyHefei, China.
[Wang, Xian] Second Affiliated Hospital of Anhui Medical University, Department of PathologyHefei, China.
[Feng, Zhenzhong] Second Affiliated Hospital of Anhui Medical University, Department of PathologyHefei, China.
[Hong, Bo] Chinese Academy of Sciences, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Anhui Province Key Laboratory of Medical Physics and TechnologyHefei, China.
[Yu, Dexin] Second Affiliated Hospital of Anhui Medical University, Department of UrologyHefei, China.
[Wang, Yi] Second Affiliated Hospital of Anhui Medical University, Department of UrologyHefei, China.
RP Wang, Y (reprint author), Second Affiliated Hospital of Anhui Medical University, Department of Urology, Hefei, China.
EM wangyi2035@ahmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610282
EP 1610289
DI 10.3389/pore.2022.1610282
PG 8
ER
PT J
AU Luo, W
Nagaria, T
Sun, H
Ma, J
Lombardo, J
Bassett, R
Cao, A
Tan, D
AF Luo, Wenyi
Nagaria, S. Teddy
Sun, Hongxia
Ma, Junsheng
Lombardo, L. Jamie
Bassett, Roland
Cao, C. Austin
Tan, Dongfeng
TI Expression and Potential Prognostic Value of SOX9, MCL-1 and SPOCK1 in Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; gastric cancer; SPOCK1; SOX9; MCL-1
ID prognosis; gastric cancer; SPOCK1; SOX9; MCL-1
AB Gastric cancer is a common malignancy and remains one of the leading causes of cancerrelated deaths, though its incidence is in decline in most developed countries. One of the major challenges of treating gastric cancer is tumor heterogeneity, which portends a high degree of prognostic variance and the necessity for different treatment modalities. Tumor heterogeneity is at least in part due to divergent differentiation of tumor cells to clones harboring different molecular alterations. Here we studied the expression of emerging prognostic markers SOX9, MCL-1, and SPOCK1 (Testican-1) in a cohort of gastric cancer by immunohistochemistry and investigated how individual biomarkers and their combinations predict disease prognosis. We found frequent expression of SPOCK1 (in both nuclei and cytoplasm), MCL-1 and SOX9 in gastric cancer. In univariate analysis, nuclear SPOCK1 expression and pathologic TNM stage were negative prognostic markers in this cohort. In multivariate analysis, SOX9 expression stood out as a predictor of poor prognosis. Further subgroup analysis suggested prognostic value of SOX9 expression in poorly differentiated gastric adenocarcinoma. MCL-1 showed no prognostic role in this cohort.
C1 [Luo, Wenyi] University of Oklahoma, Health Sciences Center, Department of PathologyOklahoma City, OK, USA.
[Nagaria, S. Teddy] The University of Texas M.D. Anderson Cancer Center, Department of PathologyHouston, TX, USA.
[Sun, Hongxia] The University of Texas M.D. Anderson Cancer Center, Department of PathologyHouston, TX, USA.
[Ma, Junsheng] The University of Texas M.D. Anderson Cancer Center, Department of BiostatisticsHouston, TX, USA.
[Lombardo, L. Jamie] The University of Texas M.D. Anderson Cancer Center, Department of PathologyHouston, TX, USA.
[Bassett, Roland] The University of Texas M.D. Anderson Cancer Center, Department of BiostatisticsHouston, TX, USA.
[Cao, C. Austin] University of Pennsylvania, School of MedicinePhiladelphia, PA, USA.
[Tan, Dongfeng] The University of Texas M.D. Anderson Cancer Center, Department of PathologyHouston, TX, USA.
RP Luo, W (reprint author), University of Oklahoma, Health Sciences Center, Department of Pathology, Oklahoma City, USA.
EM wenyi-luo@ouhsc.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD MAR
PY 2022
VL 28
IS 1
BP 1610293
EP 1610299
DI 10.3389/pore.2022.1610293
PG 7
ER
PT J
AU Chen, B
Li, R
Zhang, J
Xu, L
Jiang, F
AF Chen, Bing
Li, Rutao
Zhang, Junling
Xu, Lin
Jiang, Feng
TI Genomic Landscape of Metastatic Lymph Nodes and Primary Tumors in Non-Small-Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gene mutation; ARID1A; non-small-cell lung cancer; metastatic; CTNNB1
ID gene mutation; ARID1A; non-small-cell lung cancer; metastatic; CTNNB1
AB Objective: To investigate the genetic mutation characteristics of non-small cell lung cancers (NSCLC) with and without lymph node metastasis. Methods: Primary lesions and metastatic lymph node lesions of 36 Chinese NSCLC patients were tested for somatic mutations, tumor mutation burden, phylogenetic and clonal evolutional analysis using a 1021-gene panel by next-generation sequencing (NGS) with an average sequencing depth of 671X. Results: In this study, eighteen patients with lung adenocarcinoma (LUAD) and 18 with lung squamous cell carcinoma (LUSC) were included. Different groups had distinct characteristics of gene mutations. CTNNB1 gene mutations were only present in Nome_LC LUAD patients (p < 0.05). ARID1A mutation was however the only gene with significant alterations (p < 0.05) in Nome_LC in LUSC. Phylogenetic trees of mutated genes were also constructed. Linear and parallel evolutions of metastatic lymph nodes were observed both in LUAD and LUSC. Conclusion: LUSC exhibited more genetic mutations than LUAD. Intriguingly, there was significant difference in gene mutations between Meta_LC and Nome_LC. CTNNB1 gene alteration was the key mutation in LUAD that seems to promote proliferation of the tumor and then determine T stage. On the other hand, proliferation of the tumor was characterized by ARID1A missense mutation in LUSC, thus influencing the T stage as well. Lymph node metastasis could display both linear and parallel evolutionary characteristics in NSCLC. Different metastatic lymph nodes might have exactly the same or different mutated genes, underlining the heterogeneous genomic characteristics of these cancer types.
C1 [Chen, Bing] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical UniversityNanjing, China.
[Li, Rutao] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical UniversityNanjing, China.
[Zhang, Junling] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Xu, Lin] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical UniversityNanjing, China.
[Jiang, Feng] Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical UniversityNanjing, China.
RP Xu, L (reprint author), Jiangsu Cancer Hospital, the Affiliated Hospital of Nanjing Medical University, Nanjing, China.
EM szl_xl@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610020
EP 1610029
DI 10.3389/pore.2022.1610020
PG 10
ER
PT J
TI Methodological Challenges of Digital PCR Detection of the Histone H3 K27M Somatic Variant in Cerebrospinal Fluid
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cerebrospinal fluid; liquid biopsy; dPCR; cell-free DNA; CNS tumor; diffuse midline glioma; H3 K27M
ID cerebrospinal fluid; liquid biopsy; dPCR; cell-free DNA; CNS tumor; diffuse midline glioma; H3 K27M
AB Cell-free DNA (cfDNA) in body fluids is invaluable for cancer diagnostics. Despite the impressive potential of liquid biopsies for the diagnostics of central nervous system (CNS) tumors, a number of challenges prevent introducing this approach into routine laboratory practice. In this study, we adopt a protocol for sensitive detection of the H3 K27M somatic variant in cerebrospinal fluid (CSF) by using digital polymerase chain reaction (dPCR). Optimization of the protocol was carried out stepwise, including preamplification of the H3 target region and adjustment of dPCR conditions. The optimized protocol allowed detection of the mutant allele starting from DNA quantities as low as 9 picograms. Analytical specificity was tested using a representative group of tumor tissue samples with known H3 K27M status, and no false-positive cases were detected. The protocol was applied to a series of CSF samples collected from patients with CNS tumors (n = 18) using two alternative dPCR platforms, QX200 Droplet Digital PCR system (Bio-Rad) and QIAcuity Digital PCR System (Qiagen). In three out of four CSF specimens collected from patients with H3 K27M-positive diffuse midline glioma, both platforms allowed detection of the mutant allele. The use of ventricular access for CSF collection appears preferential, as lumbar CSF samples may produce ambiguous results. All CSF samples collected from patients with H3 wild-type tumors were qualified as H3 K27M-negative. High agreement of the quantitative data obtained with the two platforms demonstrates universality of the approach.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610024
EP 1610036
DI 10.3389/pore.2022.1610024
PG 13
ER
PT J
AU Zhang, P
Chen, L
Wu, Sh
Ye, B
Chen, Ch
Shi, L
AF Zhang, Peichen
Chen, Liping
Wu, Shengjie
Ye, Bailiang
Chen, Chao
Shi, Lingyan
TI Construction of a Metabolism-Related Long Non-Coding RNAs-Based Risk Score Model of Hepatocellular Carcinoma for Prognosis and Personalized Treatment Prediction
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; lncRNA; hepatocellular carcinoma; metabolism; therapeutic response
ID prognosis; lncRNA; hepatocellular carcinoma; metabolism; therapeutic response
AB Background: Long non-coding RNAs (lncRNAs) play a key regulatory role in tumor metabolism. Although hepatocellular carcinoma (HCC) is a metabolic disease, there have been few systematic reports on the association between lncRNA expression and metabolism in HCC. Results: In this study, we screened 557 metabolism-related lncRNAs in HCC. A risk score model based on 13 metabolism-related lncRNA pairs was constructed to predict the outcome and drug response in HCC. The risk score model presented a better prediction of the outcomes than that with common clinicopathological characteristics, such as tumor stage, grade, and status and aneuploidy score in both training and testing cohorts. In addition, patients in the high-risk group exhibited higher responses to gemcitabine and epothilone, whereas those in the low-risk group were more sensitive to metformin and nilotinib. Conclusion: The metabolism-related lncRNAs-based risk score model and the other findings of this study may be helpful for HCC prognosis and personalized treatment prediction.
C1 [Zhang, Peichen] The First Affiliated Hospital of Wenzhou Medical University, Department of Gastrointestinal SurgeryWenzhou, China.
[Chen, Liping] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Department of PharmacyHangzhou, China.
[Wu, Shengjie] Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Department of PharmacyHangzhou, China.
[Ye, Bailiang] The First Affiliated Hospital of Wenzhou Medical University, Department of GastroenterologyWenzhou, China.
[Chen, Chao] The First Affiliated Hospital of Wenzhou Medical University, Department of GastroenterologyWenzhou, China.
[Shi, Lingyan] The First Affiliated Hospital of Wenzhou Medical University, Department of GastroenterologyWenzhou, China.
RP Shi, L (reprint author), The First Affiliated Hospital of Wenzhou Medical University, Department of Gastroenterology, Wenzhou, China.
EM shilingyan@wmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610066
EP 1610075
DI 10.3389/pore.2022.1610066
PG 10
ER
PT J
AU Xia, H
Deng, L
Meng, Sh
Liu, X
Zheng, Ch
AF Xia, Hailong
Deng, Lei
Meng, Shu
Liu, Xipeng
Zheng, Chao
TI Single-Cell Transcriptome Profiling Signatures and Alterations of Microglia Associated With Glioblastoma Associate Microglia Contribution to Tumor Formation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GBM; single-sell RNA-seq; microglia; tumor immune microenvironment; aged microglia
ID GBM; single-sell RNA-seq; microglia; tumor immune microenvironment; aged microglia
AB Glioblastoma (GBM), which occasionally occurs in pediatric patients, is the most common tumor of the central nervous system in adults. Clinically, GBM is classified as low-grade to high-grade (from 1 to 4) and is characterized by late discovery, limited effective treatment methods, and poor efficacy. With the development of immunotherapy technology, effective GBM treatment strategies are of great significance. The main immune cells found in the GBM tumor microenvironment are macrophages and microglia (MG). Both these monocytes play important roles in the occurrence and development of GBM. Macrophages are recruited during tumorigenesis, whereas MG is present in the brain during embryonic development. Interestingly, the accumulation of these monocytes is inversely proportional to the survival of adult GBM patients but not the pediatric GBM patients. This study used single-cell RNA-seq data to reveal the heterogeneity of MG in tumor lesions and to explore the role of different MG subtypes in the occurrence and development of GBM. The results may help find new targets for immunotherapy of GBM.
C1 [Xia, Hailong] Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), Department of NeurosurgeryChongqing, China.
[Deng, Lei] Bishan District People’s Hospital, Department of NeurosurgeryChongqing, China.
[Meng, Shu] Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), Internal MedicineChongqing, China.
[Liu, Xipeng] Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), Department of NeurosurgeryChongqing, China.
[Zheng, Chao] Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), Department of NeurosurgeryChongqing, China.
RP Zheng, Ch (reprint author), Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), Department of Neurosurgery, Chongqing, China.
EM lemanarc@dreamway-china.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610067
EP 1610076
DI 10.3389/pore.2022.1610067
PG 10
ER
PT J
AU Egyed, B
Horvath, A
Semsei,
Szalai, Cs
Muller, J
Erdelyi, D
Kovacs, G
AF Egyed, Balint
Horvath, Anna
Semsei, F. Agnes
Szalai, F. Csaba
Muller, Judit
Erdelyi, J. Daniel
Kovacs, T. Gabor
TI Co-Detection of VEGF-A and Its Regulator, microRNA-181a, May Indicate Central Nervous System Involvement in Pediatric Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cerebrospinal fluid; biomarkers; liquid biopsy; central nervous system involvement; pediatric leukemia; enzyme-linked immunosorbent assay
ID cerebrospinal fluid; biomarkers; liquid biopsy; central nervous system involvement; pediatric leukemia; enzyme-linked immunosorbent assay
AB Central nervous system (CNS) involvement is a leading cause of therapy-refractory pediatric acute lymphoblastic leukemia (pALL), which is aggravated by underdiagnosing CNS disease with the currently used cell-based approach of cerebrospinal fluid (CSF) diagnostics. Our study focused on developing novel subcellular CNS leukemia indicators in the CSF and the bone marrow (BM) of patients with pALL. Serial liquid biopsy samples (n = 65) were analyzed by Elisas to measure the level of essential proteins associated with blast cell CNS trafficking, vascular endothelial growth factor A (VEGF-A) and integrin alpha 6 (ITGA6). In CSF samples from early induction chemotherapy, VEGF-A concentration were uniformly elevated in the CNS-positive group compared to those patients without unambiguous meningeal infiltration (9 vs Nine patients, Δc = 17.2 pg/ml, p = 0.016). Expression of miR-181a, a VEGFA-regulating microRNA which showed increased level in CNS leukemia in our previous experiments, was then paralleled with VEGF-A concentration. A slight correlation between the levels of miR-181a and VEGF-A indicators in CSF and BM samples was revealed (n = 46, Pearson’s r = 0.36, p = 0.015). After validating in international cohorts, the joint quantification of miR-181a and VEGF-A might provide a novel tool to precisely diagnose CNS involvement and adjust CNS-directed therapy in pALL.
C1 [Egyed, Balint] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Horvath, Anna] Semmelweis University, Department of Genetics, Cell- and Immunobiology, Clinical Genomics Research GroupBudapest, Hungary.
[Semsei, F. Agnes] Semmelweis University, Department of Genetics, Cell- and Immunobiology, Clinical Genomics Research GroupBudapest, Hungary.
[Szalai, F. Csaba] Semmelweis University, Department of Genetics, Cell- and Immunobiology, Clinical Genomics Research GroupBudapest, Hungary.
[Muller, Judit] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Erdelyi, J. Daniel] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
[Kovacs, T. Gabor] Semmelweis University, 2nd Department of PediatricsBudapest, Hungary.
RP Kovacs, G (reprint author), Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary.
EM kovacs.gabor1@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610096
EP 1610101
DI 10.3389/pore.2022.1610096
PG 6
ER
PT J
AU Boniface, Ch
Spellman, P
AF Boniface, T. Christopher
Spellman, T. Paul
TI Blood, Toil, and Taxoteres: Biological Determinates of Treatment-Induce ctDNA Dynamics for Interpreting Tumor Response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarkers; liquid biopsy; circulating tumor DNA; ctDNA; tumor growth; treatment response
ID biomarkers; liquid biopsy; circulating tumor DNA; ctDNA; tumor growth; treatment response
AB Collection and analysis of circulating tumor DNA (ctDNA) is one of the few methods of liquid biopsy that measures generalizable and tumor specific molecules, and is one of the most promising approaches in assessing the effectiveness of cancer care. Clinical assays that utilize ctDNA are commercially available for the identification of actionable mutations prior to treatment and to assess minimal residual disease after treatment. There is currently no clinical ctDNA assay specifically intended to monitor disease response during treatment, partially due to the complex challenge of understanding the biological sources of ctDNA and the underlying principles that govern its release. Although studies have shown preand post-treatment ctDNA levels can be prognostic, there is evidence that early, ontreatment changes in ctDNA levels are more accurate in predicting response. Yet, these results also vary widely among cohorts, cancer type, and treatment, likely due to the driving biology of tumor cell proliferation, cell death, and ctDNA clearance kinetics. To realize the full potential of ctDNA monitoring in cancer care, we may need to reorient our thinking toward the fundamental biological underpinnings of ctDNA release and dissemination from merely seeking convenient clinical correlates.
C1 [Boniface, T. Christopher] Oregon Health & Science University, Knight Cancer InstitutePortland, OR, USA.
[Spellman, T. Paul] Oregon Health & Science University, Knight Cancer InstitutePortland, OR, USA.
RP Boniface, Ch (reprint author), Oregon Health & Science University, Knight Cancer Institute, Portland, USA.
EM boniface@ohsu.edu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610103
EP 1610114
DI 10.3389/pore.2022.1610103
PG 12
ER
PT J
TI Senescence-Associated miRNAs and Their Role in Pancreatic Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE oncogene; pancreatic ductal adenocarcinoma; cellular senescence; senescence-associated miRNA; senescence bypass; tumor suppressor
ID oncogene; pancreatic ductal adenocarcinoma; cellular senescence; senescence-associated miRNA; senescence bypass; tumor suppressor
AB Replicative senescence is irreversible cell proliferation arrest for somatic cells which can be circumvented in cancers. Cellular senescence is a process, which may play two opposite roles. On the one hand, this is a natural protection of somatic cells against unlimited proliferation and malignant transformation. On the other hand, cellular secretion caused by senescence can stimulate inflammation and proliferation of adjacent cells that may promote malignancy. The main genes controlling the senescence pathways are also well known as tumor suppressors. Almost 140 genes regulate both cellular senescence and cancer pathways. About two thirds of these genes (64%) are regulated by microRNAs. Senescence-associated miRNAs can stimulate cancer progression or act as tumor suppressors. Here we review the role playing by senescence-associated miRNAs in development, diagnostics and treatment of pancreatic cancer.
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Gurbuz N, Ozpolat B. MicroRNA-based Targeted Therapeutics in Pancreatic Cancer. Anticancer Res, 2019, 39:529–32., DOI 10.21873/anticanres.13144
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610156
EP 1610167
DI 10.3389/pore.2022.1610156
PG 12
ER
PT J
AU Kertesz, G
Kallay, K
Kassa, Cs
Zombori, M
Bodo, I
Kiss, Cs
Szegedi, I
Krivan, G
AF Kertesz, Gabriella
Kallay, Krisztian
Kassa, Csaba
Zombori, Marianna
Bodo, Imre
Kiss, Csongor
Szegedi, Istvan
Krivan, Gergely
TI Case Report: A Child With Hemophilia A Serves as Donor for Hematopoietic Stem Cell Transplantation to Cure His Brother’s Severe Aplastic Anemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE hemophilia a; severe aplastic anemia (SAA); hematopoietic stem cell transplantation (HSCT); hepatitis associated bone marrow failure (HABMF); children
ID hemophilia a; severe aplastic anemia (SAA); hematopoietic stem cell transplantation (HSCT); hepatitis associated bone marrow failure (HABMF); children
AB The first-line treatment of severe aplastic anemia is allogeneic hematopoietic stem cell transplantation with a matched sibling donor. However, co-morbidities of the identical donor can make donation difficult. We present a transplantation where in parallel with the patient’s conditioning treatment, the preparation of the donor with severe hemophilia A required a special management with perioperative factor VIII substitution. Donation was successful without complications, and 18 months after transplantation, the patient and his donor are well without any long-term sequelae. To our knowledge, this is the first reported succesfull transplantation with hemophilic child serving as a bone marrow donor. The procedure did not mean a significant risk to donor health, so donors with hemophilia should not be excluded from donation.
C1 [Kertesz, Gabriella] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Kallay, Krisztian] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Kassa, Csaba] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Zombori, Marianna] Heim Pal Children’s Hospital, Hemato-Oncology UnitBudapest, Hungary.
[Bodo, Imre] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Kiss, Csongor] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Szegedi, Istvan] University of Debrecen, Medical and Health Science Center, Department of Pediatric Hematology-OncologyDebrecen, Hungary.
[Krivan, Gergely] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Bodo, I (reprint author), Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary.
EM bodoimre.md@gmail.com
CR Alonso Madrigal C, Dobon Rebollo M, Laredo de la Torre V, Palomera Bernal L, Garcia Gil FA. Liver Transplantation in Hemophilia A and VonWillebrand Disease Type 3: Perioperative Management and Post-Transplant Outcome. Rev Esp Enferm Dig, 2018, 110(8):522–6., DOI 10.17235/reed.2018.5204/2017
Hermans C, Altisent C, Batorova A, Chambost H, De Moerloose P, Karafoulidou A, et al. Replacement Therapy for Invasive Procedures in Patients with Haemophilia: Literature Review, European Survey and Recommendations. Haemophilia, 2009, 15(3):639–58., DOI 10.1111/j.1365- 2516.2008.01950.x
Lin PS, Yao YT. Perioperative Management of Hemophilia A Patients Undergoing Cardiac Surgery: A Literature Review of Published Cases. J Cardiothorac Vasc Anesth, 2020, 35:1341., DOI 10.1053/j.jvca.2020.06.074
Ljung RCR, Knobe K. How to Manage Invasive Procedures in Children with Haemophilia. Br J Haematol, 2012, 157(5):519–28., DOI 10.1111/j.1365-2141. 2012.09089.x
Garagiola I, Palla R, Peyvandi F. Risk Factors for Inhibitor Development in Severe Hemophilia a. Thromb Res, 2018, 168:20–7., DOI 10.1016/j.thromres. 2018.05.027
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Gouw SC, van der Bom JG, Ljung R, Escuriola C, Cid AR, Claeyssens-Donadel S, et al. Factor VIII Products and Inhibitor Development in Severe Hemophilia A. N Engl J Med, 2013, 368(3):231–9., DOI 10.1056/nejmoa1208024
Federici AB, Mannucci PM, Stabile F, Rossi G, Piseddu G. Orthotopic Liver Transplantation in a Patient with Severe Hemophilia A: A Life-Saving Treatment for the First Italian Case. Int J Clin Lab Res, 1995, 25(1):44–6., DOI 10.1007/bf02592576
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Tuddenham E. In Search of the Source of Factor VIII. Blood, 2014, 123(24): 3691., DOI 10.1182/blood-2014-05-568857
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610171
EP 1610175
DI 10.3389/pore.2022.1610171
PG 5
ER
PT J
AU Chen, X
Li, M
Tang, Y
Liang, Q
Hua, Ch
He, H
Song, Y
Cheng, H
AF Chen, Xianzhen
Li, Ma
Tang, Yi
Liang, Qichang
Hua, Chunting
He, Huiqin
Song, Yinjing
Cheng, Hao
TI Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RNA-sequencing; HPV 8E7; immune regulations; metabolic reprogramming; epigenetic modifications
ID RNA-sequencing; HPV 8E7; immune regulations; metabolic reprogramming; epigenetic modifications
AB Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated. Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7- overexpressed normal human epidermal keratinocytes (NHEKs). Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3, were associated with epigenetic modifications, immune regulation, and metabolic pathways. Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.
C1 [Chen, Xianzhen] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[Li, Ma] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[Tang, Yi] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[Liang, Qichang] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[Hua, Chunting] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[He, Huiqin] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of GastroenterologyHangzhou, China.
[Song, Yinjing] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
[Cheng, Hao] Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and VenereologyHangzhou, China.
RP Cheng, H (reprint author), Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Department of Dermatology and Venereology, Hangzhou, China.
EM chenghao1@zju.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610176
EP 1610186
DI 10.3389/pore.2022.1610176
PG 11
ER
PT J
TI Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer stem cells; Karanahan approach; Lewis lung carcinoma; committed tumor cells; tumor growth site; cytostatic agent; dsDNA; interstrand crosslink repair
ID cancer stem cells; Karanahan approach; Lewis lung carcinoma; committed tumor cells; tumor growth site; cytostatic agent; dsDNA; interstrand crosslink repair
AB Background and Aims: A new technology based on the chronometric administration of cyclophosphamide and complex composite double-stranded DNA-based compound, which is scheduled in strict dependence on interstrand crosslinks repair timing, and named “Karanahan”, has been developed. Being applied, this technology results in the eradication of tumor-initiating stem cells and full-scale apoptosis of committed tumor cells. In the present study, the efficacy of this novel approach has been estimated in the model of Lewis carcinoma. Methods: To determine the basic indicative parameters for the approach, the duration of DNA repair in tumor cells, as well as their distribution along the cell cycle, have been assessed. Injections were done into one or both tumors in femoral region of the engrafted mice in accordance with the developed regimen. Four series of experiments were carried out at different periods of time. The content of poorly differentiated CD34+/TAMRA+ cells in the bone marrow and peripheral blood has been determined. Immunostaining followed by the flow cytometry was used to analyze the subpopulations of immune cells. Results: The high antitumor efficacy of the new technology against the developed experimental Lewis carcinoma was shown. It was found that the therapy efficacy depended on the number of tumor growth sites, seasonal and annual peculiarities. In some experiments, a long-term remission has been reached in 70% of animals with a single tumor and in 60% with two tumors. In mice with two developed grafts, mobilization capabilities of both poorly differentiated hematopoietic cells of the host and tumor stemlike cells decrease significantly. Being applied, this new technology was shown to activate a specific immune response. There is an increase in the number of NK cell populations in the blood, tumor, and spleen, killer T cells and T helper cells in the tumor and spleen, CD11b+Ly-6C+ and CD11b+Ly-6G+ cells in the tumor. A population of mature dendritic cells is found in the tumor. Conclusion: The performed experiments indicate the efficacy of the Karanahan approach against incurable Lewis carcinoma. Thus, the discussed therapy is a new approach for treating experimental neoplasms, which has a potential as a personalized anti-tumor therapeutic approach in humans.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610180
EP 1610199
DI 10.3389/pore.2022.1610180
PG 20
ER
PT J
AU Ma, T
Wu, FH
Wu, HX
Fa, Q
Chen, Y
AF Ma, Tao
Wu, Fa-Hong
Wu, Hong-Xia
Fa, Qiong
Chen, Yan
TI Long Non-Coding RNA MCM3AP-AS1: A Crucial Role in Human Malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE cancer; biomarker; lncRNA; MCM3AP-AS1; clinical features
ID cancer; biomarker; lncRNA; MCM3AP-AS1; clinical features
AB The incidence of cancer continues to grow and is one of the leading causes of death in the world. Long noncoding RNAs (LncRNAs) is a group of RNA transcripts greater than 200 nucleotides in length, and although it cannot encode proteins, it can regulate different biological functions by controlling gene expression, transcription factors, etc. LncRNA micro-chromosome maintenance protein 3-associated protein antisense RNA 1 (MCM3AP-AS1) is involved in RNA processing and cell cycle-related functions, and MCM3AP-AS1 is dysregulated in expression in various types of cancers. This biomarker is involved in many processes related to carcinogens, such as cell proliferation, apoptosis, cell cycle, and migration. In this review, we summarize the roles of MCM3AP-AS1 in different human cancers and its biological functions with a view to providing ideas for future research.
C1 [Ma, Tao] The Affiliated Hospital of Southwest Medical University, Department of HematologyLuzhou, China.
[Wu, Fa-Hong] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Wu, Hong-Xia] Lanzhou University Second Hospital, Department of Nuclear MedicineLanzhou, China.
[Fa, Qiong] The 940th Hospital of the People’s Liberation Army Joint Service Support Force, Department of Nuclear MedicineLanzhou, China.
[Chen, Yan] The Affiliated Hospital of Southwest Medical University, Department of HematologyLuzhou, China.
RP Chen, Y (reprint author), The Affiliated Hospital of Southwest Medical University, Department of Hematology, Luzhou, China.
EM chenyan1211@swmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610194
EP 1610202
DI 10.3389/pore.2022.1610194
PG 9
ER
PT J
AU Zhang, R
Tian, X
Luo, Y
Dong, H
Tian, W
Zhang, Y
Li, D
Sun, H
Meng, Z
AF Zhang, Ruyi
Tian, Xin
Luo, Ying
Dong, Haiwei
Tian, Weijun
Zhang, Yujie
Li, Dong
Sun, Haoran
Meng, Zhaowei
TI Case Report: Recurrent Malignant Struma Ovarii With Hyperthyroidism and Metastases, A Rare Case Report and Review of the Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; surgery; struma ovarii; hyperthyroidism; CA125; thyroglobulin
ID case report; surgery; struma ovarii; hyperthyroidism; CA125; thyroglobulin
AB Background: SO (Struma ovarii) is a rare form of ovarian teratoma which originates from ovarian dermoid cysts. Due to the rarity of this disease, relevant studies might not be sufficiently documented, especially cases with hyperthyroidism and multiple metastases. Case Presentation: A 40-year-old female patient was admitted to our hospital due to management of early pregnancy along with a recurrent abdominal and pelvic mass. Contrast-enhanced CT images showed an irregular mass (10.7 × 8.6 × 12.8 cm) located in the right side from the hypogastrium to the pelvic cavity and another mass (3.8 × 3.7 cm) in the liver. Laboratory examination showed that CA125 (Carbohydrate Antigen-125) was 118.10 U/mL, Tg (thyroglobulin) was >300 ng/ml, FT4 (free thyroxine) was 22.11 pmol/L, and TSH (thyroid-stimulating hormone) was <0.004 mIU/L. She subsequently underwent liver mass dissection, omentectomy, tumor dissection, peritoneal nodule resection, as well as rectal anterior wall nodule resection. The patient was diagnosed with malignant SO (papillary type) along with multiple metastases. Also, we conducted a literature review based on 290 SO cases from 257 articles. Conclusion: This study showed that malignant SO might be prone to relapse and metastasize (a metastatic rate of 52.94%) and therefore aggressive management might need to be recommended for malignant SO. Also, laparotomy might need to be recommended for large tumors that cannot be resected by laparoscopic surgery since these tumors might be prone to rupture and thus produce peritoneal implants. Furthermore, Graves’ disease might need to be considered in the differential diagnosis.
C1 [Zhang, Ruyi] Tianjin Medical University General Hospital, Department of Nuclear MedicineTianjin, China.
[Tian, Xin] Tianjin Medical University General Hospital, Department of Nuclear MedicineTianjin, China.
[Luo, Ying] Tianjin Medical University General Hospital, Department of Obstetrics and GynecologyTianjin, China.
[Dong, Haiwei] Tianjin Medical University General Hospital, Department of Obstetrics and GynecologyTianjin, China.
[Tian, Weijun] Tianjin Medical University General Hospital, Department of General SurgeryTianjin, China.
[Zhang, Yujie] Tianjin Medical University General Hospital, Department of PathologyTianjin, China.
[Li, Dong] Tianjin Medical University General Hospital, Department of Medical ImagingTianjin, China.
[Sun, Haoran] Tianjin Medical University General Hospital, Department of Medical ImagingTianjin, China.
[Meng, Zhaowei] Tianjin Medical University General Hospital, Department of Nuclear MedicineTianjin, China.
RP Meng, Z (reprint author), Tianjin Medical University General Hospital, Department of Nuclear Medicine, Tianjin, China.
EM zmeng@tmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610221
EP 1610229
DI 10.3389/pore.2022.1610221
PG 9
ER
PT J
TI The Diagnostic Significance of CXCL13 in M2 Tumor Immune Microenvironment of Human Astrocytoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; gliomas; M2 macrophages; astrocytoma; CXCL13
ID immunohistochemistry; gliomas; M2 macrophages; astrocytoma; CXCL13
AB Background: CXCL13 may act as a mediator of tumor-associated macrophage immunity during malignant progression. Objective: The present study clarifies the clinicopathological significances of CXCL13 and its corresponding trend with M2 macrophage in human astrocytoma. Methods: The predictive potential of CXCL13 was performed using 695 glioma samples derived from TCGA lower-grade glioma and glioblastoma (GBMLGG) dataset. CXCL13 and M2 biomarker CD163 were observed by immunohistochemistry in 112 astrocytoma tissues. Results: An in-depth analysis showed that CXCL13 expression was related to the poor prognosis of glioma patients (p = 0.0002) derive fromTCGA analysis. High level of CXCL13 was detected in 43 (38.39%) astrocytoma and CXCL13/CD163 coexpression was expressed in 33 (29.46%) cases. The immunoreactivities of CXCL13 and CXCL13/ CD163 were found in the malignant lesions, which were both significantly associated with grade, patient survival, and IDH1 mutation. Single CXCL13 and CXCL13/CD163 coexpression predicted poor overall survival in astrocytoma (p = 0.0039 and p = 0.0002, respectively). Multivariate Cox regression analyses manifested CXCL13/CD163 phenotype was a significant independent prognostic indicator of patient outcome in astrocytoma (CXCL13, p = 0.0642; CXCL13/CD163, p = 0.0368). Conclusion: CXCL13 overexpression is strongly linked to CD163+ M2 infiltration in malignant astrocytoma. CXCL13/CD163 coexpression would imply M2c-related aggressive characteristics existing in astrocytoma progression could also provide predictive trends of patient outcomes.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610230
EP 1610239
DI 10.3389/pore.2022.1610230
PG 10
ER
PT J
AU Li, Y
Wang, K
Zhao, E
Li, B
Li, Sh
Dong, X
Yuan, L
Yang, H
AF Li, Yan
Wang, Kunlun
Zhao, Erjiang
Li, Bingxu
Li, Shenglei
Dong, Xiaotao
Yuan, Ling
Yang, Hui
TI Prognostic Value of Lactate Dehydrogenase in Second-Line Immunotherapy for Advanced Esophageal Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; prognosis; esophageal squamous cell carcinoma; lactate dehydrogenase; programmed death -1
ID immunotherapy; prognosis; esophageal squamous cell carcinoma; lactate dehydrogenase; programmed death -1
AB Background: Immunotherapy is recommended by the NCCN (National Comprehensive Cancer Network) guidelines as the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). Patients with advanced ESCC can benefit from immunotherapy, but the overall survival time (OS) is still not satisfactory. Therefore, it is of great importance to select effective prognostic indicators. Methods: A retrospective follow-up study was conducted from January 2018 to January 2020 among 44 patients with advanced ESCC treated with second-line immune checkpoint inhibitors (programmed death -1 blocking agents) in our hospital. The cutoff values of baseline lactate dehydrogenase (LDH), LDH level at week 8, serum albumin, hemoglobin, neutrophils, monocytes, and platelets were obtained by receiver operating characteristic (ROC) curves. The Kaplan-Meier method was used to analyze the relationship between LDH at baseline, LDH level at week 8, and LDH changes during treatment with progression-free survival (PFS) and OS time. The Cox proportional hazards model was used for univariate and multivariate analyses to determine the predictors of OS. Results: In univariate analysis, we found patients with lower baseline LDH levels (cutoff value: 200 U/L) had a better median PFS (8 months vs. 3 months; HR = 2.420, 95% CI: 1.178–4.971, p = 0.016) and OS (14 months vs. 6 months; HR = 3.637, 95% CI: 1.638–8.074, p = 0.004). The level of LDH at week 8 and the changes in LDH during treatment were not significantly associated with PFS or OS. The multivariate analyses showed that baseline LDH was an independent predictor of PFS (HR = 2.712, 95% CI: 1.147–6.409, p = 0.023) and OS (HR = 6.260, 95%CI: 2.320–16.888, p < 0.001), and the monocyte count (HR = 0.389, 95% CI: 0.162–0.934, p = 0.035) was significantly associated with OS. Conclusion: Serum LDH is a powerful independent factor for PFS and OS in advanced ESCC patients treated with anti-PD-1 therapy.
C1 [Li, Yan] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Wang, Kunlun] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Zhao, Erjiang] The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Department of BiostatisticsZhengzhou, China.
[Li, Bingxu] Anyang Tumour Hospital, Department of Radiation OncologyAnyang, China.
[Li, Shenglei] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Dong, Xiaotao] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Yuan, Ling] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
[Yang, Hui] The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation OncologyZhengzhou, China.
RP Yang, H (reprint author), The Affiliated Cancer Hospital of Zhengzhou University, Department of Radiation Oncology, Zhengzhou, China.
EM dr.huiyang@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610245
EP 1610253
DI 10.3389/pore.2022.1610245
PG 9
ER
PT J
AU Evans, H
O’Sullivan, B
Hughes, F
Charles, K
Robertson, L
Taniere, P
Diaz-Cano, S
AF Evans, Harriet
O’Sullivan, Brendan
Hughes, Frances
Charles, Kathryn
Robertson, Lee
Taniere, Philippe
Diaz-Cano, Salvador
TI PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PD-L1; urothelial bladder carcinoma; predictive marker; Pembrolizumab; Atezolizumab
ID PD-L1; urothelial bladder carcinoma; predictive marker; Pembrolizumab; Atezolizumab
AB Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer’s guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.
C1 [Evans, Harriet] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[O’Sullivan, Brendan] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[Hughes, Frances] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[Charles, Kathryn] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[Robertson, Lee] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[Taniere, Philippe] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
[Diaz-Cano, Salvador] Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic ServiceBirmingham, UK.
RP Evans, H (reprint author), Queen Elizabeth Hospital Birmingham, Molecular Pathology Diagnostic Service, Birmingham, UK.
EM harriet.evans4@nhs.net
CR Cheung CC, Barnes P, Bigras G, Boerner S, Butany J, Calabrese F, et al. Fit-forpurpose PD-L1 Biomarker Testing for Patient Selection in Immuno-Oncology: Guidelines for Clinical Laboratories from the Canadian Association of Pathologists- Association Canadienne Des Pathologistes, CAP-ACP). Appl Immunohistochem Mol Morphol, 2019, 27(10):699–714., DOI 10.1097/pai.0000000000000800
Eckstein M, Cimadamore A, Hartmann A, Lopez-Beltran A, Cheng L, Scarpelli M, et al. PD-L1 Assessment in Urothelial Carcinoma: a Practical Approach. Ann Transl Med, 2019, 7:690–22., DOI 10.21037/atm.2019.10.24
Powles T, Walker J, Andrew Williams J, Bellmunt J. The Evolving Role of PDL1 Testing in Patients with Metastatic Urothelial Carcinoma. Cancer Treat Rev, 2020, 82:101925., DOI 10.1016/j.ctrv.2019.101925
Zajac M, Scott M, Ratcliffe M, Scorer P, Barker C, Al-Masri H, et al. Concordance Among Four Commercially Available, Validated Programmed Cell Death Ligand-1 Assays in Urothelial Carcinoma. Diagn Pathol, 2019, 14(1):99–10., DOI 10.1186/s13000-019-0873-6
National Institute for Health and Care Excellence. Atezolizumab for Untreated PD-L1-Positive Advanced Urothelial Cancer when Cisplatin Is Unsuitable. last update, 2021). Available at https://www.nice.org.uk/guidance/ta739/chapter/ 1-Recommendations Oct 27, Accessed February 28, 2022)
National Institute for Health and Care Excellence.Atezolizumab for Treating Locally Advanced or Metastatic Urothelial Carcinoma after Platinum-Containing Chemotherapy. last update, 2018). Available at https://www.nice.org.uk/guidance/ ta525/chapter/1-Recommendations June 13, Accessed February 28, 2022)
European Medicines Agency, -last Update, Tecentriq/Atezolizumab. Summary of Product Characteristics. last update, 2021). Available at: https://www.ema.europa. eu/en/documents/product-information/tecentriq-epar-product-information_en.pdf Nov 10, Accessed February 28, 2022)
European Medicines Agency. Keytruda/Pembrolizumab. Summary of Product Characteristics. last update, 2022). Available at https://www.ema.europa.eu/en/ documents/product-information/keytruda-epar-product-information_en.pdf Jan 11, Accessed February 28, 2022)
Balar AV, Castellano D, O’Donnell PH, Grivas P, Vuky J, Powles T, et al. Firstline Pembrolizumab in Cisplatin-Ineligible Patients with Locally Advanced and Unresectable or Metastatic Urothelial Cancer, KEYNOTE-052): a Multicentre, Single-Arm, Phase 2 Study. Lancet Oncol, 2017, 18(11): 1483–92., DOI 10.1016/s1470-2045(17)30616-2
Fradet Y, Bellmunt J, Vaughn DJ, Lee JL, Fong L, Vogelzang NJ, et al. Randomized Phase III KEYNOTE-045 Trial of Pembrolizumab versus Paclitaxel, Docetaxel, or Vinflunine in Recurrent Advanced Urothelial Cancer: Results of >2 Years of Follow-Up. Ann Oncol, 2019, 30(6):970–6., DOI 10.1093/annonc/mdz127
Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as First-Line Treatment in Cisplatin-Ineligible Patients with Locally Advanced and Metastatic Urothelial Carcinoma: a Single-Arm, Multicentre, Phase 2 Trial. The Lancet, 2017, 389(10064):67–76., DOI 10. 1016/s0140-6736(16)32455-2
Rosenberg JE, Hoffman-Censits J, Powles T, Van Der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in Patients with Locally Advanced and Metastatic Urothelial Carcinoma Who Have Progressed Following Treatment with Platinum-Based Chemotherapy: a Single-Arm, Multicentre, Phase 2 Trial. The Lancet, 2016, 387(10031):1909–20., DOI 10.1016/s0140-6736(16)00561-4
Lee KS, Choe G. Programmed Cell Death-Ligand 1 Assessment in Urothelial Carcinoma: Prospect and Limitation. J Pathol Transl Med, 2021, 55(3): 163–70., DOI 10.4132/jptm.2021.02.22
Eckstein M, Erben P, Kriegmair MC, Worst TS, Weiss C-A, Wirtz RM, et al. Performance of the Food and Drug Administration/EMA-Approved Programmed Cell Death Ligand-1 Assays in Urothelial Carcinoma with Emphasis on Therapy Stratification for First-Line Use of Atezolizumab and Pembrolizumab. Eur J Cancer, 2019, 106:234–43., DOI 10.1016/j.ejca.2018. 11.007
Hodgson A, Slodkowska E, Jungbluth A, Liu SK, Vesprini D, Enepekides D, et al. PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma. Am J Surg Pathol, 2018, 42(8):1059–66., DOI 10.1097/pas. 0000000000001084
Schwamborn K,Ammann JU, Knuchel R, Hartmann A, Baretton G, Lasitschka F, et al. Multicentric Analytical Comparability Study of Programmed Death- Ligand 1 Expression on Tumor-Infiltrating Immune Cells and Tumor Cells in Urothelial Bladder Cancer Using Four Clinically Developed Immunohistochemistry Assays. Virchows Arch, 2019, 475(5):599–608., DOI 10.1007/s00428-019-02610-z
Tretiakova M, Fulton R, Kocherginsky M, Long T, Ussakli C, Antic T, et al. Concordance Study of PD-L1 Expression in Primary and Metastatic Bladder Carcinomas: Comparison of Four Commonly Used Antibodies and RNA Expression. Mod Pathol, 2018, 31(4):623–32., DOI 10.1038/modpathol. 2017.188
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610260
EP 1610264
DI 10.3389/pore.2022.1610260
PG 5
ER
PT J
AU Benke, M
Farkas, N
Hegyi, P
Tinusz, B
Sarlos, P
Eross, B
Szemes, K
Vorhendi, N
Szakacs, Zs
Szucs,
AF Benke, Marton
Farkas, Nelli
Hegyi, Peter
Tinusz, Benedek
Sarlos, Patricia
Eross, Balint
Szemes, Kata
Vorhendi, Nora
Szakacs, Zsolt
Szucs, Akos
TI Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE biomarker; prognosis; pancreas adenocarcinoma; carbohydrate antigen 19-9; pancreatic surgery
ID biomarker; prognosis; pancreas adenocarcinoma; carbohydrate antigen 19-9; pancreatic surgery
AB Background and Aims: Pancreatic ductal adenocarcinoma has one of theworst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serumcarbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694–0.893), showing that the preoperative carbohydrate antigen 19-9 level is a “fair” marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for “considerable” heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.
C1 [Benke, Marton] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
[Farkas, Nelli] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Hegyi, Peter] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Tinusz, Benedek] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Sarlos, Patricia] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Eross, Balint] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Szemes, Kata] University of Pecs, Medical School, First Department of Medicine, Division of GastroenterologyPecs, Hungary.
[Vorhendi, Nora] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Szakacs, Zsolt] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Szucs, Akos] Semmelweis University, 1st Department of SurgeryBudapest, Hungary.
RP Szucs, (reprint author), Semmelweis University, 1st Department of Surgery, Budapest, Hungary.
EM szucs.akos@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610266
EP 1610274
DI 10.3389/pore.2022.1610266
PG 9
ER
PT J
AU Yang, Y
Yu, J
Xiong, Y
Xiao, J
Dai, D
Zhang, F
AF Yang, Yong
Yu, Jieqing
Xiong, Yuanping
Xiao, Jiansheng
Dai, Daofeng
Zhang, Feng
TI Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarkers; prognosis; bladder cancer; differentially expressed genes; DNA damage repair genes
ID biomarkers; prognosis; bladder cancer; differentially expressed genes; DNA damage repair genes
AB Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)- DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan–Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.
C1 [Yang, Yong] Jiangxi Provincial People’s Hospital Affiliated to Nanchang Medical College, Department of Otolaryngology Head and Neck SurgeryNanchang, China.
[Yu, Jieqing] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Xiong, Yuanping] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Xiao, Jiansheng] The First Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Dai, Daofeng] Nanchang University, First Affiliated Hospital, Department of Otolaryngology-Head and Neck SurgeryNanchang, China.
[Zhang, Feng] Nanchang University, The Institute of Translational Medicine, The National Engineering Research Center for Bioengineering Drugs and the TechnologiesNanchang, China.
RP Zhang, F (reprint author), Nanchang University, The Institute of Translational Medicine, The National Engineering Research Center for Bioengineering Drugs and the Technologies, Nanchang, China.
EM fengzhang0709@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610267
EP 1610278
DI 10.3389/pore.2022.1610267
PG 12
ER
PT J
AU Brenner, S
Hartzendorf, S
Vogt, P
Maier, E
Etminan, N
Jung, E
Wick, W
Sahm, F
Winkler, F
Ratliff, M
AF Brenner, Steffen
Hartzendorf, Sebastian
Vogt, Philip
Maier, Elena
Etminan, Nima
Jung, Erik
Wick, Wolfgang
Sahm, Felix
Winkler, Frank
Ratliff, Miriam
TI Progression Patterns in Non-Contrast-Enhancing Gliomas Support Brain Tumor Responsiveness to Surgical Lesions
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor progression; astrocytoma; surgical lesioning; tumor cell network; tumor microtubes
ID tumor progression; astrocytoma; surgical lesioning; tumor cell network; tumor microtubes
AB Purpose: The overall benefit of surgical treatments for patients with glioma is undisputed. We have shown preclinically that brain tumor cells form a network that is capable of detecting damage to the tumor, and repair itself. The aim of this study was to determine whether a similar mechanism might contribute to local recurrence in the clinical setting. Methods: We evaluated tumor progression patterns of 24 initially non-contrast-enhancing gliomas that were partially resected or biopsied. We measured the distance between the new contrast enhancement developing over time, and prior surgical lesioning, and evaluated tumor network changes in response to sequential resections by quantifying tumor cells and tumor networks with specific stainings against IDH1-R132H. Results: We found that new contrast enhancement appeared within the residual, nonenhancing tumor mass in 21/24 patients (87.5%). The location of new contrast enhancement within the residual tumor region was non-random; it occurred adjacent to the wall of the resection cavity in 12/21 patients (57.1%). Interestingly, the density of the glioma cell network increased in all patient tumors between initial resection or biopsy and recurrence. In line with the histological and radiological malignization, Ki67 expression increased from initial to final resections in 14/17 cases. Conclusion: The non-random distribution of glioma malignization in patients and unidirectional increase of anatomical tumor networks after surgical procedures provides evidence that surgical lesions, in the presence of residual tumor cells, can stimulate local tumor progression and tumor cell network formation. This argues for the development of intraoperative treatments increasing the benefits from surgical resection by specifically disrupting the mechanisms of local recurrence, particularly tumor cell network functionality.
C1 [Brenner, Steffen] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
[Hartzendorf, Sebastian] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
[Vogt, Philip] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
[Maier, Elena] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
[Etminan, Nima] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
[Jung, Erik] University Hospital Heidelberg, Neurology Clinic and National Center for Tumor DiseasesHeidelberg, Germany.
[Wick, Wolfgang] University Hospital Heidelberg, Neurology Clinic and National Center for Tumor DiseasesHeidelberg, Germany.
[Sahm, Felix] University of Heidelberg, University Hospital Heidelberg, Department of NeuropathologyHeidelberg, Germany.
[Winkler, Frank] University Hospital Heidelberg, Neurology Clinic and National Center for Tumor DiseasesHeidelberg, Germany.
[Ratliff, Miriam] University of Heidelberg, University Hospital Mannheim, Department of NeurosurgeryMannheim, Germany.
RP Ratliff, M (reprint author), University of Heidelberg, University Hospital Mannheim, Department of Neurosurgery, Mannheim, Germany.
EM miriam.ratliff@umm.de
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610268
EP 1610276
DI 10.3389/pore.2022.1610268
PG 9
ER
PT J
AU Fan, X
Liu, Y
Liang, Z
Wang, Sh
Yang, J
Wu, A
AF Fan, Xin
Liu, Yanqing
Liang, Zhigang
Wang, Shanshan
Yang, Jing
Wu, Aihua
TI Diagnostic Value of Six Tumor Markers for Malignant Pleural Effusion in 1,230 Patients: A Single-Center Retrospective Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE diagnostic performance; malignant pleural effusion; tumor markers; carcinoembryonic antigen; cytokeratin 19 fragment; area under the curve
ID diagnostic performance; malignant pleural effusion; tumor markers; carcinoembryonic antigen; cytokeratin 19 fragment; area under the curve
AB Background: The diagnostic value of tumor markers in pleural effusion (PE) and serum for malignant pleural effusion (MPE) is still in debate. This study aimed to evaluate the diagnostic value of six tumor markers in PE, serum, and the corresponding PE/serum (PE/S) ratio in distinguishing MPE from benign pleural effusion (BPE). Methods: A total of 1,230 patients with PE (452 MPEs and 778 BPEs) were retrospectively included in the study. PE and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), cytokeratin 19 fragment (CYFRA 21-1), and neuron-specific enolase (NSE) were measured. The area under the curve (AUC) was used to assess the single and combined diagnostic values of the six tumor markers for MPE. Results: The levels of the six tumor markers in PE, serum, and PE/S were significantly higher in MPE than that in BPE, except for serum CA125. PE CEA showed the highest AUC [0.890 (0.871–0.907)] at a cut-off value of 3.7 ng/ml compared to any single tumor marker using receiver operating characteristic (ROC) analysis. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of PE CEA were 74.1%, 95.5%, 90.5%, 86.4%, 16.47, and 0.27, respectively. The combination of PE CEA and serum CYFRA21-1 showed the best diagnostic performance with an AUC of 0.934 (sensitivity, 79.9%; specificity, 95.7%, PPV, 90.5; PLR, 17.35) among all two or three combinations. Besides, serum CYFRA21-1 was the best diagnostic tumormarker in distinguishing cytology-negativeMPE from BPE at a cut-off value of 3.0 ng/ml. Conclusion: PE CEA was the best diagnostic tumor marker in distinguishing MPE from BPE. Serum CYFRA21-1 was the best diagnostic tumor marker in distinguishing cytology-negative MPE from BPE. The combination of PE CEA and serum CYFRA21-1 could increase the diagnostic performance in distinguishingMPE from BPE and cytology-negativeMPE fromBPE.
C1 [Fan, Xin] Ningbo First Hospital, Department of DermatologyNingbo, China.
[Liu, Yanqing] Ningbo First Hospital, Department of Laboratory MedicineNingbo, China.
[Liang, Zhigang] Ningbo First Hospital, Department of Thoracic SurgeryNingbo, China.
[Wang, Shanshan] Ningbo First Hospital, Department of Laboratory MedicineNingbo, China.
[Yang, Jing] Ningbo First Hospital, Department of Respiratory and Critical CareNingbo, China.
[Wu, Aihua] Ningbo First Hospital, Department of Laboratory MedicineNingbo, China.
RP Wu, A (reprint author), Ningbo First Hospital, Department of Laboratory Medicine, Ningbo, China.
EM wuah910602@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610280
EP 1610287
DI 10.3389/pore.2022.1610280
PG 8
ER
PT J
AU Yang, Sh
Xie, Sh
Shi, X
Su, D
He, B
Xu, Y
Liu, Z
AF Yang, Shuming
Xie, Shengzhi
Shi, Xinying
Su, Dan
He, Bo
Xu, Yang
Liu, Zhefeng
TI Characterizing HDAC Pathway Copy Number Variation in Pan-Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; copy number variation; immune; histone deacetylase; tumor characteristics
ID prognosis; copy number variation; immune; histone deacetylase; tumor characteristics
AB Background: Histone deacetylase (HDAC) plays a crucial role in regulating the expression and activity of a variety of genes associated with tumor progression and immunotherapeutic processes. The aim of this study was to characterize HDAC pathway copy number variation (CNV) in pan-cancer. Methods: A total of 10,678 tumor samples involving 33 types of tumors from The Cancer Genome Atlas (TCGA) were included in the study. Results: HDAC pathway CNV and CNV gain were identified as prognostic risk factors for pan-cancer species. The differences of tumor characteristics including tumor mutational burden, tumor neoantigen burden, high-microsatellite instability, and microsatellite stable between HDAC pathway CNV altered-type group and wild-type group varied among the various cancer species. In some cancer types, HDAC pathway CNV alteration was positively correlated with loss of heterozygosity, CNV burden, ploidy, and homologous recombination defect score markers, while it was significantly negatively correlated with immune score and stroma score. There were significant differences in immune characteristics such as major histocompatibility complex class I (MHC-I), MHC-II, chemokines, cytolytic-activity, and IFN-γ between the two groups. Immune cycle characteristics varied from one cancer type to another. Conclusion: This study reveals a tumor and immune profile of HDAC pathway CNV as well as its unlimited potential in immune prognosis.
C1 [Yang, Shuming] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
[Xie, Shengzhi] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
[Shi, Xinying] Genecast Biotechnology Co., Ltd.Wuxi, China.
[Su, Dan] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
[He, Bo] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
[Xu, Yang] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
[Liu, Zhefeng] The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of OncologyBeijing, China.
RP Liu, Z (reprint author), The Fifth Medical Center of PLA General Hospital, Senior Department of Oncology, Department of Oncology, Beijing, China.
EM lzf1220@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610288
EP 1610297
DI 10.3389/pore.2022.1610288
PG 10
ER
PT J
AU Liu, P
Jiang, Y
Zheng, X
Pan, B
Xiang, H
Zheng, M
AF Liu, Pingping
Jiang, Yinan
Zheng, Xiaojing
Pan, Baoyue
Xiang, Huiling
Zheng, Min
TI Pretreatment Systemic Immune-Inflammation Index Can Predict Response to Neoadjuvant Chemotherapy in Cervical Cancer at Stages IB2-IIB
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical cancer; prognosis; neoadjuvant chemotherapy; pathological complete response; systemic immune-inflammation index
ID cervical cancer; prognosis; neoadjuvant chemotherapy; pathological complete response; systemic immune-inflammation index
AB Background: The systemic immune-inflammation index (SII) has been identified as a predictor of chemotherapy efficacy for a variety of cancers, and we aimed to determine its ability to predict the response to chemotherapy and its long-term prognosis for patients with cervical squamous cell carcinoma (CSCC) who have underwent platinum-based neoadjuvant chemotherapy (NACT). Methods: The date from 210 patients (133 in the training cohort and 77 in the validation cohort) with CSCC who received NACT were analyzed retrospectively. The association between SII and the pathological complete response (pCR) was determined using Pearson’s chi-square test, receiver operating characteristic (ROC) curve, and Logistic regression analysis. The Kaplan-Meier method and Cox proportional regression model were used to assess the relationship between SII and progression-free survival (PFS) or overall survival (OS). Results: The calculated optimal SII cutoff values for pCR and survival were 568.7051 and 600.5683, respectively, and patients were divided into two groups: a low SII group (≤568.7051 or ≤600.5683) and a high SII group (>568.7051 or >600.5683). A high SII was associated significantly with a lower pCR. Further analysis determined that SII was a more efficient predictor of pCR than the prognostic nutritional index, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Upon multivariate logistic analysis, SII proved to be an independent risk factor to predict the pCR of patients with CSCC. Kaplan-Meier analysis demonstrated that PFS and OS rates were significantly higher in the low-SII group compared with those in the high-SII group. Additional multivariate analysis indicated that the SII is an independent prognostic factor for patients with CSCC treated with NACT. Conclusion: The results confirmed that the pre-treatment SII is not only an independent predictor of pCR but also an independent prognostic factor of CSCC patients treated with platinum based NACT.
C1 [Liu, Pingping] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Jiang, Yinan] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Zheng, Xiaojing] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Pan, Baoyue] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Xiang, Huiling] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
[Zheng, Min] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of GynecologyGuangzhou, China.
RP Zheng, M (reprint author), Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecology, Guangzhou, China.
EM zhengmin@sysucc.org.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610294
EP 1610305
DI 10.3389/pore.2022.1610294
PG 12
ER
PT J
AU Ladanyi, A
Hegyi, B
Balatoni, T
Liszkay, G
Rohregger, R
Waldnig, Ch
Dudas, J
Ferrone, S
AF Ladanyi, Andrea
Hegyi, Barbara
Balatoni, Timea
Liszkay, Gabriella
Rohregger, Raphael
Waldnig, Christoph
Dudas, Jozsef
Ferrone, Soldano
TI HLA Class I Downregulation in Progressing Metastases of Melanoma Patients Treated With Ipilimumab
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; melanoma; ipilimumab; HLA class I expression; longitudinal study
ID immunotherapy; melanoma; ipilimumab; HLA class I expression; longitudinal study
AB Characterization of the molecular mechanisms underlying antitumor immune responses and immune escape mechanisms has resulted in the development of more effective immunotherapeutic strategies, including immune checkpoint inhibitor (ICI) therapy. ICIs can induce durable responses in patients with advanced cancer in a wide range of cancer types, however, the majority of the patients fail to respond to this therapy or develop resistance in the course of the treatment. Information about the molecular mechanisms underlying primary and acquired resistance is limited. Although HLA class I molecules are crucial in the recognition of tumor antigens by cytotoxic T lymphocytes, only a few studies have investigated the role of their expression level on malignant cells in ICI resistance. To address this topic, utilizing immunohistochemical staining with monoclonal antibodies (mAbs) we analyzed HLA class I expression level in pre-treatment and post-treatment tumor samples from melanoma patients treated with ipilimumab. Twenty-nine metastases removed from six patients were available for the study, including 18 pre-treatment and 11 post-treatment lesions. Compared to metastases excised before ipilimumab therapy, post-treatment lesions displayed a significantly lower HLA class I expression level on melanoma cells; HLA class I downregulation was most marked in progressing metastases from nonresponding patients. We also evaluated the level of infiltration by CD8+ T cells and NK cells but did not find consistent changes between pre- and post-treatment samples. Our results indicate the potential role of HLA class I downregulation as a mechanism of ICI resistance.
C1 [Ladanyi, Andrea] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Hegyi, Barbara] Orszagos Onkologiai Intezet, Mellkasi es Hasuregi Daganatok es Klinikai Farmakologiai OsztalyBudapest, Hungary.
[Balatoni, Timea] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Rohregger, Raphael] Medical University Innsbruck, Department of OtorhinolaryngologyInnsbruck, Austria.
[Waldnig, Christoph] Medical University Innsbruck, Department of OtorhinolaryngologyInnsbruck, Austria.
[Dudas, Jozsef] Medical University Innsbruck, Department of OtorhinolaryngologyInnsbruck, Austria.
[Ferrone, Soldano] Massachusetts General Hospital, Harvard Medical School, Department of SurgeryBoston, MA, USA.
RP Ladanyi, A (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Budapest, Hungary.
EM ladanyi.andrea@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610297
EP 1610304
DI 10.3389/pore.2022.1610297
PG 8
ER
PT J
AU Gao, L
Chen, G
Liang, ZQ
Li, JD
Li, DM
Tang, YL
Tang, D
Huang, ZG
Chen, JH
Luo, JY
Zeng, JH
Dang, YW
Feng, ZB
AF Gao, Li
Chen, Gang
Liang, Zi-Qian
Li, Jian-Di
Li, Dong-Ming
Tang, Yu-Lu
Tang, Deng
Huang, Zhi-Guang
Chen, Jun-Hong
Luo, Jia-Yuan
Zeng, Jiang-Hui
Dang, Yi-Wu
Feng, Zhen-Bo
TI Expression Profile and Molecular Basis of Cyclin-Dependent Kinases Regulatory Subunit 2 in Endometrial Carcinoma Detected by Diversified Methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE molecular mechanism; endometrial carcinoma; RNA-seq; CKS2; in-house tissue microarray
ID molecular mechanism; endometrial carcinoma; RNA-seq; CKS2; in-house tissue microarray
AB Purpose: Our purpose was to systematically appraise the clinicopathological significance and explore the molecular bases of CKS2 in endometrial carcinoma. Patients and Methods: We measured the clinicopathological significance of CKS2 using diverse methods of public RNA-seq, microarrays, and in-house tissue microarrays to investigate the molecular basis of CKS2 in endometrial carcinoma through upstream transcriptional analysis, immune infiltration correlation analysis, and co-expression analysis. Results: Both the analysis for public RNA-seq plus the microarray data and in-house tissue microarray confirmed the significant overexpression of CKS2 in a total of 1,021 endometrial carcinoma samples compared with 279 non-cancer endometrium samples (SMD = 2.10, 95% CI = 0.72–3.48). The upregulated CKS2 was significantly related to the lymph node metastasis and advanced clinical grade of endometrial carcinoma patients (p < 0.001). Mutation types such as amplification and mRNA occurred with high frequency in the CKS2 gene in endometrial carcinoma patients. A series of miRNAs and transcription factors, such as hsa-miR-26a, hsa-miR-130a, hsa-miR-30, E2F4, MAX, and GABPA, were predicted to regulate the transcription and expression of CKS2. Significant links were found between CKS2 expression and the infiltration level of B cells, CD4+ T cells, and neutrophils in endometrial carcinoma. CKS2-coexpressed genes were actively involved in pathways such as the mitotic cell cycle process, PID aurora B pathway, and prolactin signaling pathway. Conclusion: The overexpressed CKS2 showed positive correlations with the clinical progression of endometrial carcinoma and was associated with various cancer-related biological processes and pathways, showing potential as a promising clinical biomarker for endometrial carcinoma.
C1 [Gao, Li] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Chen, Gang] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Liang, Zi-Qian] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Li, Jian-Di] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Li, Dong-Ming] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Tang, Yu-Lu] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Tang, Deng] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Huang, Zhi-Guang] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Chen, Jun-Hong] Guangxi Maternal and Child Health Hospital, Department of PathologyNanning, China.
[Luo, Jia-Yuan] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Zeng, Jiang-Hui] The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People’s Hospital, Department of Clinical LaboratoryNanning, China.
[Dang, Yi-Wu] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Feng, Zhen-Bo] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
RP Feng, ZB (reprint author), The First Affiliated Hospital of Guangxi Medical University, Department of Pathology, Nanning, China.
EM fengzhenbo_gxmu@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610307
EP 1610319
DI 10.3389/pore.2022.1610307
PG 13
ER
PT J
TI Detection and Quantification of ctDNA for Longitudinal Monitoring of Treatment in Non-Small Cell Lung Cancer Patients Using a Universal Mutant Detection Assay by Denaturing Capillary Electrophoresis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE liquid biopsy; NSCLC; ctDNA; KRAS mutations; minimal residual disease; capillary electrophoresis; TP53 mutations
ID liquid biopsy; NSCLC; ctDNA; KRAS mutations; minimal residual disease; capillary electrophoresis; TP53 mutations
AB Background: Observation of anticancer therapy effect by monitoring of minimal residual disease (MRD) is becoming an important tool in management of non-small cell lung cancer (NSCLC). The approach is based on periodic detection and quantification of tumorspecific somatic DNA mutation in circulating tumor DNA (ctDNA) extracted from patient plasma. For such repetitive testing, complex liquid-biopsy techniques relying on ultra-deep NGS sequencing are impractical. There are other, cost-effective, methods for ctDNA analysis, typically based on quantitative PCR or digital PCR, which are applicable for detecting specific individual mutations in hotspots. While such methods are routinely used in NSCLC therapy prediction, however, extension to cover broader spectrum of mutations (e.g., in tumor suppressor genes) is required for universal longitudinal MRD monitoring. Methods: For a set of tissue samples from 81 NSCLC patients we have applied a denaturing capillary electrophoresis (DCE) for initial detection of somatic mutations within 8 predesigned PCR amplicons covering oncogenes and tumor suppressor genes. Mutationnegative samples were then subjected to a large panel NGS sequencing. For each patient mutation found in tissue was then traced over time in ctDNA by DCE. Results: In total we have detected a somatic mutation in tissue of 63 patients. For those we have then prospectively analyzed ctDNA from collected plasma samples over a period of up to 2 years. The dynamics of ctDNA during the initial chemotherapy therapy cycles as well as in the long-term follow-up matched the clinically observed response. Conclusion: Detection and quantification of tumor-specific mutations in ctDNA represents a viable complement to MRD monitoring during therapy of NSCLC patients. The presented approach relying on initial tissue mutation detection by DCE combined with NGS and a subsequent ctDNA mutation testing by DCE only represents a cost-effective approach for its routine implementation.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610308
EP 1610317
DI 10.3389/pore.2022.1610308
PG 10
ER
PT J
AU Polk, N
Budai, B
Hitre, E
Patocs, A
Mersich, T
AF Polk, Nandor
Budai, Barna
Hitre, Erika
Patocs, Attila
Mersich, Tamas
TI High Neutrophil-To-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammation Index (SII) Are Markers of Longer Survival After Metastasectomy of Patients With Liver-Only Metastasis of Rectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE neutrophil-to-lymphocyte ratio; liver-only metastases of rectal cancer; metastasectomy; relapse-free survival; systemic immune-inflammation index; liver-only metastases of colon cancer; preoperative treatment
ID neutrophil-to-lymphocyte ratio; liver-only metastases of rectal cancer; metastasectomy; relapse-free survival; systemic immune-inflammation index; liver-only metastases of colon cancer; preoperative treatment
AB Background: The literature data regarding colon cancer patients with liver-only metastases (CLM) show that NLR determined before metastasectomy is a prognostic marker of shorter relapse-free survival (RFS), but no results has been reported to date for rectal cancer patients with liver-only metastases (RLM). This study aimed to investigate the NLR and SII in CLM and RLM. Methods: Relapse-free (RFS) and overall survival (OS) were evaluated in 67 CLM and 103 RLM patients with a median follow-up of 46.5 and 59.8 months, respectively. Pre- and/or postoperative chemotherapy ± targeted treatment was applied in 96% and 87% of CLM and RLM patients, respectively. The cut-off level for hematologic parameters were determined by receiver operating characteristic (ROC) analysis. Univariate analysis was performed by Kaplan-Meier method and log rank test. For multivariate analysis Cox regression was applied. Results: In univariate analysis low NLR (cut-off 2) and SII (535) were predictors of longer RFS in case of CLM (p < 0.01). In contrast, for RLMhigh NLR (2.42) and SII (792) were predictors of longer RFS (p < 0.001). For RLM both NLR and SII proved to be independent markers of RFS (HR 0.66 (95% CI 0.52–0.84) and 0.73 (0.57–0.91), respectively) and OS (0.76 (0.58–0.99) and 0.66 (0.5–0.87), respectively). Only NLR (1.44 (1.04–1.99)) was independent marker of RFS for CLM. The preoperative treatment has not influenced the role of NLR or SII. Conclusion: In contrast to CLM, in RLM the high NLR or SII determined before metastasectomy proved to be independent prognostic factors of longer RFS and OS.
C1 [Polk, Nandor] Orszagos Onkologiai Intezet, Emlo- es Lagyreszsebeszeti OsztalyBudapest, Hungary.
[Budai, Barna] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Hitre, Erika] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai OsztalyBudapest, Hungary.
[Patocs, Attila] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Mersich, Tamas] Orszagos Onkologiai Intezet, Emlo- es Lagyreszsebeszeti OsztalyBudapest, Hungary.
RP Budai, B (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Budapest, Hungary.
EM budai.barna@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610315
EP 1610328
DI 10.3389/pore.2022.1610315
PG 14
ER
PT J
AU Sipos, F
Bohusne Barta, B
Simon,
Nagy, L
Danko, T
Raffay, ER
Petovari, G
Zsiros, V
Wichmann, B
Sebestyen, A
Muzes, Gy
AF Sipos, Ferenc
Bohusne Barta, Bettina
Simon, Agnes
Nagy, Lorinc
Danko, Titanilla
Raffay, Eszter Regina
Petovari, Gabor
Zsiros, Viktoria
Wichmann, Barnabas
Sebestyen, Anna
Muzes, Gyorgyi
TI Survival of HT29 Cancer Cells Is Affected by IGF1R Inhibition via Modulation of Self-DNA-Triggered TLR9 Signaling and the Autophagy Response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE autophagy; CD133; IGF1R; TLR9; HT29 cancer cell; self-DNA
ID autophagy; CD133; IGF1R; TLR9; HT29 cancer cell; self-DNA
AB Purpose: In HT29 colon cancer cells, a close interplay between self-DNA-induced TLR9 signaling and autophagy response was found, with remarkable effects on cell survival and differentiation. IGF1R activation drives the development and malignant progression of colorectal cancer. IGF1R inhibition displays a controversial effect on autophagy. The interrelated roles of IGF1R inhibition and TLR9/autophagy signaling in HT29 cancer cells have not yet been clarified. In our study, we aimed to investigate the complex interplay of IGF1R inhibition and TLR9/autophagy signaling in HT29 cells. Methods: HT29 cells were incubated with tumor-originated self-DNA with or without inhibitors of IGF1R (picropodophyllin), autophagy (chloroquine), and TLR9 (ODN2088), respectively. Cell proliferation and metabolic activity measurements, direct cell counting, NanoString and Taqman gene expression analyses, immunocytochemistry, WES Simple Western blot, and transmission electron microscopy investigations were performed. Results: The concomitant use of tumor-derived self-DNA and IGF1R inhibitors displays anti-proliferative potential, which can be reversed by parallel TLR9 signaling inhibition. The distinct effects of picropodophyllin, ODN2088, and chloroquine per se or in combination on HT29 cell proliferation and autophagy suggest that either the IGF1R-associated or nonassociated autophagy machinery is “Janus-faced” regarding its actions on cell proliferation. Autophagy, induced by different combinations of self-DNA and inhibitors is not sufficient to rescue HT29 cells from death but results in the survival of some CD133- positive stem-like HT29 cells. Conclusion: The creation of new types of combined IGF1R, autophagy, and/or TLR9 signaling inhibitors would play a significant role in the development of more personalized anti-tumor therapies for colorectal cancer.
C1 [Sipos, Ferenc] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Bohusne Barta, Bettina] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Simon, Agnes] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Nagy, Lorinc] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Raffay, Eszter Regina] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Zsiros, Viktoria] Semmelweis University, 1st Department of AnatomyBudapest, Hungary.
[Wichmann, Barnabas] Lufthansa Systems HungariaBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Muzes, Gyorgyi] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
RP Sipos, F (reprint author), Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary.
EM sipos.ferenc@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610322
EP 1610336
DI 10.3389/pore.2022.1610322
PG 15
ER
PT J
AU Li, L
Song, Q
Cao, D
Jiao, Y
Yuan, G
Song, Y
AF Li, Lihong
Song, Qianqian
Cao, Dandan
Jiao, Yuchen
Yuan, Guangwen
Song, Yan
TI Whole-Exome Sequencing Could Distinguish Primary Pulmonary Squamous Cell Carcinoma From Lung Metastases in Individuals With Cervical Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE metastasis; cervix; squamous cell carcinoma; sequence; lung
ID metastasis; cervix; squamous cell carcinoma; sequence; lung
AB Aims: Metastatic cervical carcinoma is hard to cure using traditional treatment and new therapeutic approaches are needed. However, the process of clonal evolution and the molecular alterations that contribute to tumor progression from primary to metastatic carcinoma remain unclear. It is currently difficult to distinguish between the primary pulmonary squamous cell carcinoma (PPSCC) and metastatic cervical squamous cell carcinoma (CSCC). Methods: Paired primary CSCC and lung/lymph nodes metastatic lesions from eight patients were analyzed by whole-exome sequencing (WES). WES data of matched specimens and normal samples were aligned to the human reference genome and analyzed to identify somatic mutations in primary and metastatic lesions. Results: A total of 1,254 somatic variants were identified. All the primary lesions and metastatic lesions shared mutations, the percentage of shared mutations between primary lesions and corresponding metastatic lesions varied significantly, ranging from6%to 70%. In other words, all the metastatic lesions are clonally related to primary lesions, confirming WES could prove they are metastatic from the cervix but not PPSCC. We tried to apply a gene panel to help distinguish PPSCC and metastatic CSCC but failed because the mutations were widely distributed in CSCC. Interestingly, lymph nodes metastasis (LNM) harbored fewer cancer driver mutations than primary CSCC specimens with a significant difference. Besides this, there was no significant difference in somatic mutations and copy number variation (CNV) between primary and metastatic CSCC. Conclusion: Our data demonstrate that WES is an additional helpful tool in distinguishing PPSCC and metastatic CSCC, especially for certain difficult cases.
C1 [Li, Lihong] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Song, Qianqian] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, State Key Lab of Molecular Oncology, Laboratory of Cell and Molecular BiologyBeijing, China.
[Cao, Dandan] Genetron Health (Beijing) Co. Ltd.Beijing, China.
[Jiao, Yuchen] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, State Key Lab of Molecular Oncology, Laboratory of Cell and Molecular BiologyBeijing, China.
[Yuan, Guangwen] Chinese Academy of Medvdical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Department of Gynecology OncologyBeijing, China.
[Song, Yan] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
RP Song, Y (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of Pathology, Beijing, China.
EM songyan@cicams.ac.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610325
EP 1610332
DI 10.3389/pore.2022.1610325
PG 8
ER
PT J
AU Chen, Z
Zhou, H
Hu, H
Chen, L
AF Chen, Zhe
Zhou, Hong
Hu, Haoliang
Chen, Linxi
TI Blocking the Metabolic Switch Toward Cytosolic 1C Flux: A Novel Therapeutic Approach for Tumors With Low SLC19A1 Expression
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE One-carbon units; SHMT1; SHMT2; RPMI; TSH; MTHFD1
ID One-carbon units; SHMT1; SHMT2; RPMI; TSH; MTHFD1
C1 [Chen, Zhe] University of South China, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, College of Basic Medical Science, Hengyang Medical School, Institute of Pharmacy and PharmacologyHengyang, China.
[Zhou, Hong] The First Affiliated Hospital of University of South China, Radiology DepartmentHengyang, China.
[Hu, Haoliang] Hunan University of Arts and Science, College of Life and Environmental Sciences, Changde Research Centre for Artificial Intelligence and BiomedicineChangde, China.
[Chen, Linxi] University of South China, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, College of Basic Medical Science, Hengyang Medical School, Institute of Pharmacy and PharmacologyHengyang, China.
RP Hu, H (reprint author), Hunan University of Arts and Science, College of Life and Environmental Sciences, Changde Research Centre for Artificial Intelligence and Biomedicine, Changde, China.
EM haolianghu6@126.com
CR Ducker GS, Chen L, Morscher RJ, Ghergurovich JM, EspositoM, Teng X, et al. Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway. Cell Metab, 2016, 24(4):640–1., DOI 10.1016/ j.cmet.2016.09.011
Lee WD, Pirona AC, Sarvin B, Stern A, Nevo-Dinur K, Besser E, et al. Tumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availability. Cell Metab, 2020, 33:190–8., DOI 10.1016/j.cmet.2020. 12.002
Paone A, Marani M, Fiascarelli A, Rinaldo S, Giardina G, Contestabile R, et al. SHMT1 Knockdown Induces Apoptosis in Lung Cancer Cells by Causing Uracil Misincorporation. Cell Death Dis, 2014, 5:e1525., DOI 10.1038/cddis. 2014.482
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610337
EP 1610341
DI 10.3389/pore.2022.1610337
PG 5
ER
PT J
AU Nagy, Zs
Ferenczi, K
Istenes, I
Eid, H
Bodor, Cs
Timar, B
Demeter, J
AF Nagy, F. Zsofia
Ferenczi, Kata
Istenes, Ildiko
Eid, Hanna
Bodor, Csaba
Timar, Botond
Demeter, Judit
TI Case Report: Development of Diffuse Large B Cell Lymphoma a Long Time After Hairy Cell Leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE hairy cell leukaemia; non-Hodgkin lymphoma; diffuse large B cell lymphoma; transformation; case report
ID hairy cell leukaemia; non-Hodgkin lymphoma; diffuse large B cell lymphoma; transformation; case report
AB Hairy cell leukaemia (HCL) is a rare B cell malignancy with an indolent course leading to pancytopaenia due to bone marrow infiltration. It has been proposed that HCL patients are at risk of developing a secondary malignancy, with a marked likelihood of the development of other hematologic malignancies including Hodgkin lymphoma and high-grade non- Hodgkin lymphomas. Here, we present the case of two patients who developed diffuse large B cell lymphoma after a long course of hairy cell leukaemia. In the case of the female patient, we report on the occurrence of a third malignant disease, which is very uncommon. With our case descriptions we contribute to the very small number of similar cases reported.
C1 [Nagy, F. Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Ferenczi, Kata] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Istenes, Ildiko] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Eid, Hanna] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Timar, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Budapest, Hungary.
EM timar.botond@med.semmelweis-univ.hu
CR Cross M, Dearden C. Hairy Cell Leukaemia. Curr Oncol Rep, 2020, 22:42., DOI 10.1007/s11912-020-00911-0
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Else M, Ruchlemer R, Osuji N, Del Giudice I, Matutes E, Woodman A, et al. Long Remissions in Hairy Cell Leukemia with Purine Analogs. Cancer, 2005, 104:2442–8., DOI 10.1002/cncr.21447
Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, et al. BRAF Mutations in Hairy-Cell Leukemia. N Engl J Med, 2011, 364:2305–15., DOI 10.1056/NEJMoa1014209.BRAF
Chihara D, Kreitman RJ. Treatment of Hairy Cell Leukemia. Expert Rev Hematol, 2020, 13:1107–17., DOI 10.1080/17474086.2020.1819231
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610338
EP 1610342
DI 10.3389/pore.2022.1610338
PG 5
ER
PT J
AU Ujfaludi, Zs
Kuthi, L
Pankotai-Bodo, G
Banko, S
Sukosd, F
Pankotai, T
AF Ujfaludi, Zsuzsanna
Kuthi, Levente
Pankotai-Bodo, Gabriella
Banko, Sarolta
Sukosd, Farkas
Pankotai, Tibor
TI Novel Diagnostic Value of Driver Gene Transcription Signatures to Characterise Clear Cell Renal Cell Carcinoma, ccRCC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE ccRCC; gene expression signature; tumour profiling; driver gene; statistical analyses
ID ccRCC; gene expression signature; tumour profiling; driver gene; statistical analyses
AB Routine molecular tumour diagnostics are augmented by DNA-based qualitative and quantitative molecular techniques detecting mutations of DNA. However, in the past decade, it has been unravelled that the phenotype of cancer, as it’s an extremely complex disease, cannot be fully described and explained by single or multiple genetic variants affecting only the coding regions of the genes. Moreover, studying the manifestation of these somatic mutations and the altered transcription programming—driven by genomic rearrangements, dysregulation of DNA methylation and epigenetic landscape—standing behind the tumorigenesis and detecting these changes could provide a more detailed characterisation of the tumour phenotype. Consequently, novel comparative cancer diagnostic pipelines, including DNA- and RNA-based approaches, are needed for a global assessment of cancer patients. Here we report, that by monitoring the expression patterns of key tumour driver genes by qPCR, the normal and the tumorous samples can be separated into distinct categories. Furthermore, we also prove that by examining the transcription signatures of frequently affected genes at 3p25, 3p21 and 9p21.3 genomic regions, the ccRCC (clear cell renal cell carcinoma) and non-tumorous kidney tissues can be distinguished based on the mRNA level of the selected genes. Our results open new diagnostics possibilities where the mRNA signatures of tumour drivers can supplement the DNA-based approaches providing a more precise diagnostics opportunity leading to determine more precise therapeutic protocols.
C1 [Ujfaludi, Zsuzsanna] University of Szeged, Department of PathologySzeged, Hungary.
[Kuthi, Levente] University of Szeged, Department of PathologySzeged, Hungary.
[Pankotai-Bodo, Gabriella] University of Szeged, Department of PathologySzeged, Hungary.
[Banko, Sarolta] University of Szeged, Department of PathologySzeged, Hungary.
[Sukosd, Farkas] University of Szeged, Department of PathologySzeged, Hungary.
[Pankotai, Tibor] University of Szeged, Department of PathologySzeged, Hungary.
RP Pankotai, T (reprint author), University of Szeged, Department of Pathology, Szeged, Hungary.
EM pankotai.tibor@szte.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610345
EP 1610357
DI 10.3389/pore.2022.1610345
PG 13
ER
PT J
AU Matrai, Z
Kelemen, P
Kosa, Cs
Maraz, R
Paszt, A
Pavlovics, G
Savolt,
Simonka, Zs
Toth, D
Kasler, M
Vicko, F
Pluta, P
Kolacinska-Wow, A
Murawa, D
Jankau, J
Ciesla, S
Dyttert, D
Sabol, M
Zhygulin, A
Avetisyan, A
Lazar, Gy
AF Matrai, Zoltan
Kelemen, Peter
Kosa, Csaba
Maraz, Robert
Paszt, Attila
Pavlovics, Gabor
Savolt, Akos
Simonka, Zsolt
Toth, Dezso
Kasler, Miklos
Vicko, Ferenc
Pluta, Piotr
Kolacinska-Wow, Agnieszka
Murawa, Dawid
Jankau, Jerzy
Ciesla, Slawomir
Dyttert, Daniel
Sabol, Martin
Zhygulin, Andrii
Avetisyan, Artur
Lazar, Gyorgy
TI Modern Breast Cancer Surgery 1st Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Guideline
DE breast cancer; surgery; consensus statement; oncoplastic surgery; oncology
ID breast cancer; surgery; consensus statement; oncoplastic surgery; oncology
AB This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.
C1 [Matrai, Zoltan] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Kelemen, Peter] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Kosa, Csaba] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
[Maraz, Robert] Bacs-Kiskun County HospitalKecskemet, Hungary.
[Paszt, Attila] University of Szeged, Department of SurgerySzeged, Hungary.
[Pavlovics, Gabor] University of Pecs, Department of SurgeryPecs, Hungary.
[Savolt, Akos] National Institute of Oncology, Department of SurgeryBudapest, Hungary.
[Simonka, Zsolt] University of Szeged, Department of SurgerySzeged, Hungary.
[Toth, Dezso] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
[Kasler, Miklos] Government of Hungary, Minister of Human CapacitiesBudapest, Hungary.
[Vicko, Ferenc] University of Novi Sad, Medical Faculty Novi Sad, Oncology Institute of Vojvodina Sremska KamenicaNovi Sad, Serbia.
[Pluta, Piotr] Polish Mother’s Memorial Hospital - Research Institute, Department of Oncological Surgery and Breast DiseasesLodz, Poland.
[Kolacinska-Wow, Agnieszka] Medical University of Lodz, department of Head and Neck Cancer SurgeryLodz, Poland.
[Murawa, Dawid] Poznan University of Medical Sciences, Department of Oncology, Department of Oncological SurgeryPoznan, Poland.
[Jankau, Jerzy] Medical University of Gdansk, University Hospitals, Plastic Surgery DepartmentGdansk, Poland.
[Ciesla, Slawomir] Karol Marcinkowski University Hospital, General and Oncological Surgery ClinicZielona Gora, Poland.
[Dyttert, Daniel] Comenius University, Medical Faculty, St. Elisabeth Cancer Institute, Department of Surgical OncologyBratislava, Slovakia.
[Sabol, Martin] Comenius University, Medical Faculty, St. Elisabeth Cancer Institute, Department of Surgical OncologyBratislava, Slovakia.
[Zhygulin, Andrii] LISOD Hospital of Israeli OncologyKyiv, Ukraine.
[Avetisyan, Artur] National Center of OncologyYerevan, Armenia.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
RP Matrai, Z (reprint author), National Institute of Oncology, Department of Surgery, Budapest, Hungary.
EM matraidoc@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610377
EP 1610395
DI 10.3389/pore.2022.1610377
PG 19
ER
PT J
AU Polgar, Cs
Kahan, Zs
Ivanov, O
Chorvath, M
Ligacova, A
Csejtei, A
Gabor, G
Landherr, L
Mangel, L
Mayer,
Fodor, J
AF Polgar, Csaba
Kahan, Zsuzsanna
Ivanov, Olivera
Chorvath, Martin
Ligacova, Andrea
Csejtei, Andras
Gabor, Gabriella
Landherr, Laszlo
Mangel, Laszlo
Mayer, Arpad
Fodor, Janos
TI Radiotherapy of Breast Cancer— Professional Guideline 1st Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Guideline
DE breast cancer; radiotherapy; guidelines; radiation oncology; consensus
ID breast cancer; radiotherapy; guidelines; radiation oncology; consensus
AB The international radiotherapy (RT) expert panel has revised and updated the RT guidelines that were accepted in 2020 at the 4th Hungarian Breast Cancer Consensus Conference, based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (stage 0), as RT decreases the risk of local recurrence (LR) by 50–60%. In early stage (stage I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor-positive tumour, hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives to conventional WBI administered for 5 weeks. Following mastectomy, RT significantly decreases the risk of LR and improves overall survival of patients who have 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant systemic treatment (NST) followed by BCS, WBI is mandatory, while after NST followed by mastectomy, locoregional RT should be given in cases of initial stage III–IV and ypN1 axillary status.
C1 [Polgar, Csaba] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Ivanov, Olivera] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Chorvath, Martin] Slovak Medical University, St. Elisabeth Cancer Institute, Department of Radiation OncologyBratislava, Slovakia.
[Ligacova, Andrea] Slovak Medical University, St. Elisabeth Cancer Institute, Department of Radiation OncologyBratislava, Slovakia.
[Csejtei, Andras] Vas Megyei Markusovszky Korhaz, OnkoradiologiaSzombathely, Hungary.
[Gabor, Gabriella] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Landherr, Laszlo] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Mangel, Laszlo] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Mayer, Arpad] Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Onkoradiologiai KozpontBudapest, Hungary.
[Fodor, Janos] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
RP Polgar, Cs (reprint author), National Institute of Oncology, Center of Radiotherapy, Budapest, Hungary.
EM polgar.csaba@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610378
EP 1610392
DI 10.3389/pore.2022.1610378
PG 15
ER
PT J
AU Forrai, G
Kovacs, E
Ambrozay,
Barta, M
Borbely, K
Lengyel, Zs
Ormandi, K
Pentek, Z
Tunde, T
Eva, S
AF Forrai, Gabor
Kovacs, Eszter
Ambrozay, Eva
Barta, Miklos
Borbely, Katalin
Lengyel, Zsolt
Ormandi, Katalin
Pentek, Zoltan
Tunde, Tasnadi
Eva, Sebo
TI Use of Diagnostic Imaging Modalities in Modern Screening, Diagnostics and Management of Breast Tumours 1st Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Guideline
DE mammography; breast ultrasound; breast MRI; breast screening; conventional nuclear medicine; SPECT/CT; PET/CT; biopsy
ID mammography; breast ultrasound; breast MRI; breast screening; conventional nuclear medicine; SPECT/CT; PET/CT; biopsy
AB Breast radiologists and nuclear medicine specialists updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference in Kecskemet. A recommendation is hereby made that breast tumours should be screened, diagnosed and treated according to these guidelines. These professional guidelines include the latest technical developments and research findings, including the role of imaging methods in therapy and follow-up. It includes details on domestic development proposals and also addresses related areas (forensic medicine, media, regulations, reimbursement). The entire material has been agreed with the related medical disciplines.
C1 [Forrai, Gabor] GE-RAD Kft.Budapest, Hungary.
[Kovacs, Eszter] GE-RAD Kft.Budapest, Hungary.
[Ambrozay, Eva] MaMMa Egeszsegugyi RtBudapest, Hungary.
[Barta, Miklos] Royal Cornwall HospitalTruro, UK.
[Borbely, Katalin] National Institute of OncologyBudapest, Hungary.
[Lengyel, Zsolt] Hamad Medical CorporationDoha, Qatar.
[Ormandi, Katalin] University of SzegedSzeged, Hungary.
[Pentek, Zoltan] MaMMa Egeszsegugyi RtBudapest, Hungary.
[Tunde, Tasnadi] Rethy Pal HospitalBekescsaba, Hungary.
[Eva, Sebo] Kenezy Teaching HospitalDebrecen, Hungary.
RP Forrai, G (reprint author), GE-RAD Kft., Budapest, Hungary.
EM drforraigabor@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610382
EP 1610405
DI 10.3389/pore.2022.1610382
PG 24
ER
PT J
AU Xu, R
Ke, X
Shang, W
Liu, Sh
Fu, X
Wang, T
Jin, Sh
AF Xu, Rui
Ke, Xing
Shang, Wenwen
Liu, Shuna
Fu, Xin
Wang, Ting
Jin, Shuxian
TI Distribution and Clinical Significance of IL-17A in Tumor-Infiltrating Lymphocytes of Non-Small Cell Lung Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NSCLC; TILs; Th17 cells; Tc17 cells; γδT cells; IL-17
ID NSCLC; TILs; Th17 cells; Tc17 cells; γδT cells; IL-17
AB Objective: To investigate the distribution of IL-17A and its clinical significance in tumor infiltrating lymphocytes (TILs) of patients with non-small cell lung cancer (NSCLC). Methods: Expression level of IL-17A in TILs of 3 paired NSCLC and paracancerous specimens was measured by qRT-PCR. The distribution of IL-17A in immune cell subsets of 15 paired NSCLC and paracancerous specimens was examined by flow cytometry. The correlation between IL-17A and clinical features of NSCLC was identified. Results: IL-17A was significantly upregulated in TILs of NSCLC specimens than those of paracancerous ones (p < 0.0001). Meanwhile, T helper 17 cells (Th17 cells, p < 0.001), IL- 17-secreting CD8+ T cells (Tc17 cells, p < 0.001) and IL-17-producing cells (γδT17 cells, p < 0.0001) were significantly abundant in TILs of NSCLC specimens than those of controls, and the higher abundance of the latter was much pronounced than that of the former two. Moreover, γδT17 cells in TILs were significantly correlated with lymphatic metastasis and CYFRA 21-1 level of NSCLC patients (p < 0.05). Conclusion: Tumor infiltrated γδT cells are the main source of IL-17 in early-stage NSCLC, and IL-17 may be a vital regulator involved in the development of NSCLC.
C1 [Xu, Rui] The First Affiliated Hospital of Nanjing Medical University, Department of Laboratory MedicineNanjing, China.
[Ke, Xing] Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, Department of Clinical LaboratoryShanghai, China.
[Shang, Wenwen] The First Affiliated Hospital of Nanjing Medical University, Department of Laboratory MedicineNanjing, China.
[Liu, Shuna] The First Affiliated Hospital of Nanjing Medical University, Department of Laboratory MedicineNanjing, China.
[Fu, Xin] The First Affiliated Hospital of Nanjing Medical University, Department of Laboratory MedicineNanjing, China.
[Wang, Ting] The First Affiliated Hospital of Nanjing Medical University, Department of Laboratory MedicineNanjing, China.
[Jin, Shuxian] The First Affiliated Hospital of Nanjing Medical University, Department of Respiratory and Critical Care MedicineNanjing, China.
RP Jin, Sh (reprint author), The First Affiliated Hospital of Nanjing Medical University, Department of Respiratory and Critical Care Medicine, Nanjing, China.
EM jin_sx@aliyun.com
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Corsale AM, Di Simone M, Lo Presti E, Picone C, Dieli F, Meraviglia S. Metabolic Changes in Tumor Microenvironment: How Could They Affect γδ T Cells Functions? Cells, 2021, 10(11):2896., DOI 10.3390/ cells10112896
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Hurtado CG, Wan F, Housseau F, Sears CL. Roles for Interleukin 17 and Adaptive Immunity in Pathogenesis of Colorectal Cancer. Gastroenterology, 2018, 155(6):1706–15., DOI 10.1053/j.gastro.2018.08.056
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610384
EP 1610390
DI 10.3389/pore.2022.1610384
PG 7
ER
PT J
AU Wang, Sh
Yu, A
Han, M
Chen, X
Li, Z
Ke, M
Cai, X
Ai, M
Xing, Y
AF Wang, Shun
Yu, Aihua
Han, Mengyao
Chen, Xiaomin
Li, Zhi
Ke, Min
Cai, Xiaojun
Ai, Ming
Xing, Yiqiao
TI Pathological Changes and Expression of JAK-STAT Signaling Pathway Hallmark Proteins in Rat Retinas at Different Time Points After Retinal Ischemia Reperfusion Injury
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; pathology; retina ischemia reperfusion injury; retinal ganglion cells; Janus kinase signal transducer and activator of transcription
ID apoptosis; pathology; retina ischemia reperfusion injury; retinal ganglion cells; Janus kinase signal transducer and activator of transcription
AB Retinal ischemia reperfusion injury (RIRI) is a conventional pathological process in various retinal vascular diseases. Many studies select only one specific time point to apply drugs and then assess the therapeutic effect of drugs; however, the baselines are not the same at different time points, which may cause variation in the judgement. Therefore, further investigation is needed. Accordingly, this study aimed to investigate the pathological changes of retinal structure, expression of JAK-STAT signaling pathway hallmark proteins, and apoptosis at different time points after retinal ischemia reperfusion injury in rats. Sixtysix male SPF Sprague-Dawley rats were randomly divided into six groups: control group, RIRI 0, 6-, 24-, 72-, and 144-h groups. RIRI models were induced by perfusing equilibrium solution into the right eye anterior chamber to increase intraocular pressure to 110 mmHg for 60 min. Rats were sacrificed at different time points after reperfusion. Then hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, western blot, and TUNEL were used. Hematoxylin-eosin showed the pathological changes while transmission electron microscope revealed the ultra-structure changes of retina after RIRI. Immunohistochemistry showed that JAK2, STAT3, p-JAK2, p-STAT3, Bax, and Bcl-2 proteins mainly located in ganglion cell layer and inner nuclear layer, the relative expression of former five proteins had significant differences vs. control group (p < 0.05), while Bcl-2 had no significant difference. In western blot, the protein expressing of JAK2, STAT3, p-JAK2, p-STAT3, p-Akt, and Bax had significant differences vs. control group (p < 0.05), while Akt and Bcl-2 had no significant differences. TUNEL staining showed the number of apoptosis positive cells rose initially but declined later, with a peak value at RIRI 24 h group. The dynamic changes of hallmark proteins at different time points after RIRI indicate that JAK-STAT signaling pathway activates rapidly but weakens later and plays a vital role in RIRI, and apoptosis is involved in RIRI with a peak value at 24 h in the process, suggesting a potential therapeutic direction and time window for treating RIRI.
C1 [Wang, Shun] Renmin Hospital of Wuhan University, Eye CenterWuhan, China.
[Yu, Aihua] Renmin Hospital of Wuhan University, Eye CenterWuhan, China.
[Han, Mengyao] Wuhan Aier Eye Hospital of Wuhan University, Retinal and Vitreous Diseases DepartmentWuhan, China.
[Chen, Xiaomin] Zhongnan Hospital of Wuhan University, Department of OphthalmologyWuhan, China.
[Li, Zhi] Zhongnan Hospital of Wuhan University, Department of OphthalmologyWuhan, China.
[Ke, Min] Zhongnan Hospital of Wuhan University, Department of OphthalmologyWuhan, China.
[Cai, Xiaojun] Zhongnan Hospital of Wuhan University, Department of OphthalmologyWuhan, China.
[Ai, Ming] Renmin Hospital of Wuhan University, Eye CenterWuhan, China.
[Xing, Yiqiao] Renmin Hospital of Wuhan University, Eye CenterWuhan, China.
RP Ai, M (reprint author), Renmin Hospital of Wuhan University, Eye Center, Wuhan, China.
EM wan@whu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610385
EP 1610393
DI 10.3389/pore.2022.1610385
PG 9
ER
PT J
AU Kahan, Zs
Szanto, I
Dudas, R
Kapitany, Zs
Molnar, M
Koncz, Zs
Mailath, M
AF Kahan, Zsuzsanna
Szanto, Istvan
Dudas, Rita
Kapitany, Zsuzsanna
Molnar, Maria
Koncz, Zsuzsa
Mailath, Monika
TI Breast Cancer Survivorship Programme: Follow-Up, Rehabilitation, Psychosocial Oncology Care. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Guideline
DE follow-up; healthy lifestyle; physical rehabilitation; psychosocial oncology care; social rehabilitation; side-effect management
ID follow-up; healthy lifestyle; physical rehabilitation; psychosocial oncology care; social rehabilitation; side-effect management
AB Follow-up includes ongoing contact with and health education of the patient, surveillance and control of the adverse effects of surgery, oncological therapies or radiotherapy, screening of metachronous cancers, and comprehensive (physical, psychological and social) patient rehabilitation, which may be enhanced by a healthy lifestyle. Primary attention should be paid to early detection and, when needed, curative treatment of local/regional tumour recurrences. Similarly, with the hope of curative solution, it is important to recognize the entity of a low-mass and relatively indolent recurrence or metastasis (oligometastasis); however, there is still no need to investigate distant metastases by routine diagnostic imaging or assess tumour markers. Below there is a list of possible sources of support, with respect to adjuvant hormone therapy continued during long-term care, social support resources, pivotal points and professional opportunities for physical and mental rehabilitation. Individual solutions for specific issues (breast cancer risk/genetic mutation, pregnancy) are provided by constantly widening options. Ideally, a complex breast cancer survivorship programme is practised by a specially trained expert supported by a cooperative team of oncologists, surgeons, breast radiologists, social workers, physiotherapists, psychooncologists and psychiatrists. The approach of follow-up should be comprehensive and holistic.
C1 [Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Szanto, Istvan] Fejer County Szent Gyorgy HospitalSzekesfehervar, Hungary.
[Dudas, Rita] University of Szeged, Department of OncotherapySzeged, Hungary.
[Kapitany, Zsuzsanna] Semmelweis University, Department of PhysiotherapyBudapest, Hungary.
[Molnar, Maria] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Koncz, Zsuzsa] Semmelweis University, Institute of Behavioural SciencesBudapest, Hungary.
[Mailath, Monika] University of Debrecen, Department of OncologyDebrecen, Hungary.
RP Kahan, Zs (reprint author), University of Szeged, Department of Oncotherapy, Szeged, Hungary.
EM kahan.zsuzsanna@med.u-szeged.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610391
EP 1610404
DI 10.3389/pore.2022.1610391
PG 14
ER
PT J
AU Siozopoulou, V
Marcq, E
De Winne, K
Norga, K
Schmitz, G
Duwel, V
Delvenne, P
Smits, E
Pauwels, P
AF Siozopoulou, Vasiliki
Marcq, Elly
De Winne, Koen
Norga, Koen
Schmitz, Gertjan
Duwel, Valerie
Delvenne, Philippe
Smits, Evelien
Pauwels, Patrick
TI NTRK Fusions in a Sarcomas Series: Pathology, Molecular and Clinical Aspects
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sarcoma; prognosis; NTRK fusion; TRK immunohistochemistry; NTRK fusion partner; histology
ID sarcoma; prognosis; NTRK fusion; TRK immunohistochemistry; NTRK fusion partner; histology
AB Targeting molecular alterations has been proven to be an inflecting point in tumor treatment. Especially in recent years, inhibitors that target the tyrosine receptor kinase show excellent response rates and durable effects in all kind of tumors that harbor fusions of one of the three neurotrophic tyrosine receptor kinase genes (NTRK1, NTRK2 and NTRK3). Today, the therapeutic options in most metastatic sarcomas are rather limited. Therefore, identifying which sarcoma types are more likely to harbor these targetable NTRK fusions is of paramount importance. At the moment, identification of these fusions is solely based on immunohistochemistry and confirmed by molecular techniques. However, a first attempt has been made to describe the histomorphology of NTRK-fusion positive sarcomas, in order to pinpoint which of these tumors are the best candidates for testing. In this study, we investigate the immunohistochemical expression of pan-TRK in 70 soft tissue and bone sarcomas. The pan-TRK positive cases were further investigated with molecular techniques for the presence of a NTRK fusion. Seven out of the 70 cases showed positivity for pan-TRK, whereas two of these seven cases presented an NTRK3 fusion. Further analysis of the fused sarcomas revealed some unique histological, molecular and clinical findings. The goal of this study is to expand the histomorphological spectrum of the NTRK-fused sarcomas, to identify their fusion partners and to correlate these parameters with the clinical outcome of the disease. In addition, we evaluated the immunohistochemical expression pattern of the pan-TRK and its correlation with the involved NTRK gene.
C1 [Siozopoulou, Vasiliki] Antwerp University Hospital, Department of PathologyEdegem, Belgium.
[Marcq, Elly] University of Antwerp, Integrated Personalized and Precision Oncology Network (IPPON), Center for Oncological Research (CORE)Wilrijk, Belgium.
[De Winne, Koen] Antwerp University Hospital, Department of PathologyEdegem, Belgium.
[Norga, Koen] Antwerp University Hospital, Department of PediatricsEdegem, Belgium.
[Schmitz, Gertjan] Hospital of Klina, Department of OrthopaedicsAntwerp, Belgium.
[Duwel, Valerie] Hospital of Klina, Department of PathologyAntwerp, Belgium.
[Delvenne, Philippe] CHU Sart Tilman, Department of AnatomopathologyLiege, Belgium.
[Smits, Evelien] University of Antwerp, Integrated Personalized and Precision Oncology Network (IPPON), Center for Oncological Research (CORE)Wilrijk, Belgium.
[Pauwels, Patrick] Antwerp University Hospital, Department of PathologyEdegem, Belgium.
RP Siozopoulou, V (reprint author), Antwerp University Hospital, Department of Pathology, Edegem, Belgium.
EM vasiliki.siozopoulou@uantwerpen.be
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Brcic I, Godschachner TM, Bergovec M, Igrec J, Till H, Lackner H, et al. Broadening the Spectrum of NTRK Rearranged Mesenchymal Tumors and Usefulness of Pan-TRK Immunohistochemistry for Identification of NTRK Fusions. Mod Pathol, 2021, 34(2):396–407., DOI 10.1038/s41379-020- 00657-x
Davis JL, Lockwood CM, Stohr B, Boecking C, Al-Ibraheemi A, DuBois SG, et al. Expanding the Spectrum of Pediatric NTRK-Rearranged Mesenchymal Tumors. Am J Surg Pathol, 2019, 43(4):435–45., DOI 10.1097/PAS. 0000000000001203
Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D, et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol, 2017, 41(11):1547–51., DOI 10. 1097/PAS.0000000000000911
Solomon JP, Benayed R, Hechtman JF, Ladanyi M. Identifying Patients with NTRK Fusion Cancer. Ann Oncol, 2019, 30(Suppl. l_8):viii16–viii22., DOI 10. 1093/annonc/mdz384
Nozzoli F, Lazar AJ, Castiglione F, Campanacci DA, Beltrami G, De Logu F, et al. NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities. Pathol Oncol Res. 2022;28., DOI 10.3389/pore.2022.1610237
Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO, et al. Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. Am J Surg Pathol, 2018, 42(7):927–35., DOI 10.1097/PAS.0000000000001062
Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, et al. NTRK Fusion Detection across Multiple Assays and 33,997 Cases: Diagnostic Implications and Pitfalls. Mod Pathol, 2020, 33(1):38–46., DOI 10.1038/s41379- 019-0324-7
Hung YP, Fletcher CDM, Hornick JL. Evaluation of Pan-TRK Immunohistochemistry in Infantile Fibrosarcoma, Lipofibromatosis-like Neural Tumour and Histological Mimics. Histopathology, 2018, 73(4): 634–44., DOI 10.1111/his.13666
Csanyi-Bastien M, Lanic M-D, Beaussire L, Ferric S, Francois A, Meseure D, et al. Pan-TRK Immunohistochemistry Is Highly Correlated with NTRK3 Gene Rearrangements in Salivary Gland Tumors. Am J Surg Pathol, 2021, 45: 1487–98., DOI 10.1097/PAS.0000000000001718
Suurmeijer AJH, Dickson BC, Swanson D, Zhang L, Sung Y-S, Cotzia P, et al. A Novel Group of Spindle Cell Tumors Defined by S100 and CD34 Coexpression Shows Recurrent Fusions Involving RAF1, BRAF, and NTRK1/2 Genes. Genes Chromosomes Cancer, 2018, 57(12):611–21., DOI 10.1002/gcc. 22671
Suurmeijer AJ, Dickson BC, Swanson D, Zhang L, Sung YS, Huang HY, et al. The Histologic Spectrum of Soft Tissue Spindle Cell Tumors with NTRK3 Gene Rearrangements. Genes Chromosomes Cancer, 2019, 58(11):739–46., DOI 10.1002/gcc.22767
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610423
EP 1610430
DI 10.3389/pore.2022.1610423
PG 8
ER
PT J
AU Fogarasi, IA
Benczik, M
Moravcsik-Kornyicki,
Kocsis, A
Gyulai, A
Kosa, Zs
AF Fogarasi, Istvan Andras
Benczik, Marta
Moravcsik-Kornyicki, Agota
Kocsis, Adrienn
Gyulai, Aniko
Kosa, Zsigmond
TI The Prevalence of High-Risk Human Papillomavirus in Hungary —A Geographically Representative, Cross-Sectional Study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical cancer; cancer screening; cross-sectional studies; genotype; human papillomavirus infection; human papillomavirus vaccines; prevalence studies; rural population
ID cervical cancer; cancer screening; cross-sectional studies; genotype; human papillomavirus infection; human papillomavirus vaccines; prevalence studies; rural population
AB Background: The estimated age-standardized incidence and mortality rates of cervical cancer in Hungary are substantially higher than the European average. In many countries, human papillomavirus (HPV) testing is the first-line method of cervical cancer screening in women >30 years. According to the European guidelines, evidence-based improvement of a national prevention strategy requires the monitoring of representative data. Methods: ThinPrep cervical samples were collected over a period of 8months at 84 sampling sites, including 4,000 eligible samples with valid laboratory results from the screening target population of females aged 25–65 years, with addresses in the representative geographic area (19 counties and four major settlement types). Genotyping of high-risk HPV (hrHPV) was performed using the Confidence HPV-X (Neumann Diagnostics) and Linear Array HPV Genotyping (Roche) tests. Demographic data were collected using a questionnaire, enabling the analysis of hrHPV genotype distribution by age, geography, education, and HPV vaccination. Results: Overall, 446 samples were hrHPV-positive, showing a prevalence of 11.15% (9.73% age-representative), similar to the world average, higher than the European average, and lower than the Eastern-European average. After age standardization, no significant geographic differences were found, except for low hrHPV prevalence in villages (p = 0.036) and in those with elementary education (p = 0.013). Following genotypes 16 and 31, in order of frequency, certain non-vaccine hrHPV genotypes (HPV51, 66, 56) showed unexpectedly higher prevalence than international data. Conclusion: Our study provides the first geographically representative genotype-specific hrHPV prevalence baseline database in Hungary to support policy-making efforts. Significant correlations with demographic data have transferable conclusions.
C1 [Fogarasi, Istvan Andras] SYNLAB Hungary Ltd., SYNLAB Genoid Molecular Diagnostic LaboratoryBudapest, Hungary.
[Benczik, Marta] SYNLAB Hungary Ltd., SYNLAB Genoid Molecular Diagnostic LaboratoryBudapest, Hungary.
[Moravcsik-Kornyicki, Agota] University of Debrecen, Department of Health Visitors Methodology and PreventionNyiregyhaza, Hungary.
[Kocsis, Adrienn] SYNLAB Hungary Ltd., SYNLAB Genoid Molecular Diagnostic LaboratoryBudapest, Hungary.
[Gyulai, Aniko] University of Miskolc, Institute of Applied Health Sciences, Department of Preventive Health SciencesMiskolc, Hungary.
[Kosa, Zsigmond] University of Debrecen, Department of Health Visitors Methodology and PreventionNyiregyhaza, Hungary.
RP Fogarasi, IA (reprint author), SYNLAB Hungary Ltd., SYNLAB Genoid Molecular Diagnostic Laboratory, Budapest, Hungary.
EM andras.fogarasi.dr@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610424
EP 1610432
DI 10.3389/pore.2022.1610424
PG 9
ER
PT J
AU Zheng, P
Gao, H
Xie, X
Lu, P
AF Zheng, Peiming
Gao, Huijie
Xie, Xuanhu
Lu, Peipei
TI Plasma Exosomal hsa_circ_0015286 as a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; gastric cancer; diagnosis; CircRNA; exosomes
ID biomarker; gastric cancer; diagnosis; CircRNA; exosomes
AB Circular RNA (circRNA) is stable and abundant in exosomes as a potential biomarker for the diagnosis and prognosis of tumor. In this study, cancer specific exosomal circRNAs were identified through circRNA microarray, and 58 circRNAs were significantly upregulated in cancer cells derived exosomes. Then 60 patients with newly diagnosed gastric cancer (GC), 30 chronic gastritis patients and 30 healthy subjects were enrolled for further clinical validation. We detected that hsa_circ_0015286 was remarkably highly expressed in GC tissue, plasma and cancer cells compared with normal controls. Results of ROC curve analysis showed that the area under curve (AUC) of hsa_circ_0015286, CEA and CA 19-9 was 0.778, 0.673, and 0.665, respectively. The combined detection of three indicators had the highest AUC (0.843). Exosomal hsa_circ_0015286 expression was closely associated with tumor size, TNM stage and lymph node metastasis. The expression level of exosomal hsa_circ_0015286 in GC patients decreased significantly after surgery. Overall survival of patients with low hsa_circ_0015286 expression was longer than those with high expression. Our data demonstrated that exosomal hsa_circ_0015286 might be a promising noninvasive biomarker for the diagnosis and prognosis evaluation of GC.
C1 [Zheng, Peiming] Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical LaboratoryZhengzhou, China.
[Gao, Huijie] The First Affiliated Hospital of Henan University, Department of OncologyKaifeng, China.
[Xie, Xuanhu] The First Affiliated Hospital of Henan University, Department of OncologyKaifeng, China.
[Lu, Peipei] The First Affiliated Hospital of Henan University, Department of OncologyKaifeng, China.
RP Zheng, P (reprint author), Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Department of Clinical Laboratory, Zhengzhou, China.
EM zpm8266@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610446
EP 1610453
DI 10.3389/pore.2022.1610446
PG 8
ER
PT J
AU Zhang, K
Gao, L
Wang, J
Chu, X
Zhang, Z
Zhang, Y
Fang, F
Tao, Y
Li, X
Tian, Y
Li, Z
Sang, X
Ma, L
Lu, L
Chen, Y
Yu, J
Zhuo, R
Wu, Sh
Pan, J
Hu, Sh
AF Zhang, Kunlong
Gao, Li
Wang, Jianwei
Chu, Xinran
Zhang, Zimu
Zhang, Yongping
Fang, Fang
Tao, Yanfang
Li, Xiaolu
Tian, Yuanyuan
Li, Zhiheng
Sang, Xu
Ma, Li
Lu, Lihui
Chen, Yanling
Yu, Juanjuan
Zhuo, Ran
Wu, Shuiyan
Pan, Jian
Hu, Shaoyan
TI A Novel BRD Family PROTAC Inhibitor dBET1 Exerts Great Anti-Cancer Effects by Targeting c-MYC in Acute Myeloid Leukemia Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE acute myeloid leukemia; C-MYC; BRD4; dBET1; PROTAC
ID acute myeloid leukemia; C-MYC; BRD4; dBET1; PROTAC
AB Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysistargeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML.
C1 [Zhang, Kunlong] Children’s Hospital of Soochow UniversitySuzhou, China.
[Gao, Li] Children’s Hospital of Soochow University, Department of HaematologySuzhou, China.
[Wang, Jianwei] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Chu, Xinran] Children’s Hospital of Soochow University, Department of HaematologySuzhou, China.
[Zhang, Zimu] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Zhang, Yongping] Children’s Hospital of Soochow UniversitySuzhou, China.
[Fang, Fang] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Tao, Yanfang] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Li, Xiaolu] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Tian, Yuanyuan] Children’s Hospital of Soochow University, Department of HaematologySuzhou, China.
[Li, Zhiheng] Children’s Hospital of Soochow UniversitySuzhou, China.
[Sang, Xu] Children’s Hospital of Soochow UniversitySuzhou, China.
[Ma, Li] Children’s Hospital of Soochow UniversitySuzhou, China.
[Lu, Lihui] Children’s Hospital of Soochow UniversitySuzhou, China.
[Chen, Yanling] Children’s Hospital of Soochow UniversitySuzhou, China.
[Yu, Juanjuan] Children’s Hospital of Soochow UniversitySuzhou, China.
[Zhuo, Ran] Children’s Hospital of Soochow UniversitySuzhou, China.
[Wu, Shuiyan] Children’s Hospital of Soochow University, Intensive Care UnitSuzhou, China.
[Pan, Jian] Children’s Hospital of Soochow University, Institute of Pediatric ResearchSuzhou, China.
[Hu, Shaoyan] Children’s Hospital of Soochow University, Department of HaematologySuzhou, China.
RP Pan, J (reprint author), Children’s Hospital of Soochow University, Institute of Pediatric Research, Suzhou, China.
EM panjian2008@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610447
EP 1610457
DI 10.3389/pore.2022.1610447
PG 11
ER
PT J
AU Luo, D
Liao, S
Liu, Y
Lin, Y
Li, Y
Liao, X
AF Luo, Dongcheng
Liao, Sina
Liu, Yu
Lin, Youzhi
Li, Yongqiang
Liao, XiaoLi
TI Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HJURP; hepatocellular carcinoma; tumor microenvironment; prognosis; GSEA; WGCNA; RNA-seq; single-cell RNA-seq
ID HJURP; hepatocellular carcinoma; tumor microenvironment; prognosis; GSEA; WGCNA; RNA-seq; single-cell RNA-seq
AB Background: Hepatocellular carcinoma is the most common type of primary liver cancer, and it is associated with poor prognosis. It often fails to respond to immunotherapy, highlighting the need to identify genes that are associated with the tumor microenvironment and may be good therapeutic targets. We and others have shown that the Holliday cross-recognition protein HJURP can promote the proliferation, migration, and invasion by hepatocellular carcinoma cells, and that HJURP overexpression is associated with poor survival. Here we explored the potential relationship between HJURP and the tumor microenvironment in hepatocellular carcinoma. Methods: We used the Immuno-Oncology-Biological-Research (IOBR) software package to analyze the potential roles of HJURP in the tumor microenvironment. Using single-cell RNA sequencing data, we identified the cell clusters expressing abundant HJURP, then linked some of these clusters to certain bioprocesses using Gene Set Enrichment Analysis (GSEA). We validated the differential expression of HJURP in tumor-infiltrating CD8+ T cells, sorted by flow cytometry into populations based on the expression level of PD-1. We used weighted gene co-expression network analysis (WGCNA) to identify immunity-related genes whose expression strongly correlated with that of HJURP. The function of these genes was validated based on enrichment in Gene Ontology (GO) terms, and they were used to establish a prognosis prediction model. Results: IOBR analysis suggested that HJURP is significantly related to the immunosuppressive tumor microenvironment and was significantly related to T cells, dendritic cells, and B cells. Based on single-cell RNA sequencing, HJURP was strongly expressed in T cells, erythrocytes, and B cells from normal liver tissues, as well as in CD8+ T cells, dendritic cells, and one cluster of hepatocytes in hepatocellular carcinoma tissues. Malignant hepatocytes strongly expressing HJURP were associated with the downregulation of immune bioprocesses. HJURP expression was significantly higher in CD8+ T cells strongly expressing PD-1 than in those expressing no or intermediate levels of PD1. WGCNA identified two module eigengenes (comprising 397 and 84 genes) related to the tumor microenvironment. We identified 24 hub genes and confirmed that they were related to immune regulation. A prognostic risk score model based on expression of HJURP, PPT1, PML, and CLEC7A showed moderate ability to predict survival. Conclusion: HJURP is associated with tumor-infiltrating immune cells, immune checkpoints, and immune suppression in hepatocellular carcinoma. HJURP-related genes involved in immune responses may be useful for predicting patient prognosis.
C1 [Luo, Dongcheng] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Liao, Sina] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Liu, Yu] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Lin, Youzhi] Guangxi Medical University Cancer Hospital, Hepatobiliary Surgery DepartmentNanning, China.
[Li, Yongqiang] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Liao, XiaoLi] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
RP Liao, X (reprint author), Guangxi Medical University Cancer Hospital, Department of First Chemotherapy, Nanning, China.
EM nllxl@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610506
EP 1610524
DI 10.3389/pore.2022.1610506
PG 19
ER
PT J
AU Deme, D
Kovacs, S
Telekes, A
AF Deme, Daniel
Kovacs, Sandor
Telekes, Andras
TI Corrigendum: Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE overall survival; advanced cancer; serum biomarkers; prognostic importance; CRP; albumin; PLR
ID overall survival; advanced cancer; serum biomarkers; prognostic importance; CRP; albumin; PLR
AB A Corrigendum on Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination by Deme D, Kovacs S and Telekes A (2022). Pathol. Oncol. Res. 28:1610004. doi: 10.3389/pore.2022.1610004
C1 [Deme, Daniel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Kovacs, Sandor] University of Debrecen, Department of Economical and Financial MathematicsDebrecen, Hungary.
[Telekes, Andras] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
RP Deme, D (reprint author), Szent Lazar Megyei Korhaz, Onkologiai Osztaly, Salgotarjan, Hungary.
EM danieldeme_md@ymail.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUN
PY 2022
VL 28
IS 2
BP 1610517
EP 1610518
DI 10.3389/pore.2022.1610517
PG 2
ER
PT J
AU Chen, W
Zhang, F
Xu, H
Hou, X
Tang, D
Dai, Y
AF Chen, Wenbiao
Zhang, Feng
Xu, Huixuan
Hou, Xianliang
Tang, Donge
Dai, Yong
TI Identification and Characterization of Genes Related to the Prognosis of Hepatocellular Carcinoma Based on Single-Cell Sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gene; hepatocellular carcinoma; prognostic model; single-cell sequencing; molecular cluster
ID gene; hepatocellular carcinoma; prognostic model; single-cell sequencing; molecular cluster
AB The heterogeneity of hepatocellular carcinoma (HCC) highlights the importance of precision therapy. In recent years, single-cell RNA sequencing has been used to reveal the expression of genes at the single-cell level and comprehensively study cell heterogeneity. This study combined big data analytics and single-cell data mining to study the influence of genes on HCC prognosis. The cells and genes closely related to the HCC were screened through single-cell RNA sequencing (71,915 cells, including 34,414 tumor cells) and big data analysis. Comprehensive bioinformatics analysis of the key genes of HCC was conducted formolecular classification and multi-dimensional correlation analyses, and a prognostic model for HCC was established. Finally, the correlation between the prognosticmodel and clinicopathological features was analyzed. 16,880 specific cells, screened from the single-cell expression profile matrix, were divided into 20 sub-clusters. Cell typing revealed that 97% of these cells corresponded to HCC cell lines, demonstrating the high specificity of cells derived from single-cell sequencing. 2,038 genes with high variability were obtained. The 371 HCC samples were divided into two molecular clusters. Cluster 1 (C1) was associated with tumorigenesis, high immune score, immunotherapy targets (PD-L1 and CYLA-4), high pathological stage, and poor prognosis. Cluster 2 (C2) was related to metabolic and immune function, low immune score, low pathological stage, and good prognosis. Seven differentially expressed genes (CYP3A4, NR1I2, CYP2C9, TTR, APOC3, CYP1A2, and AFP) identified between the two molecular clusters were used to construct a prognosticmodel.We further validated the correlation between the seven key genes and clinical features, and the established prognostic model could effectively predict HCC prognosis. Our study identified seven key genes related to HCC that were used to construct a prognostic model through single-cell sequencing and big data analytics. This study provides new insights for further research on clinical targets of HCC and new biomarkers for clinical application.
C1 [Chen, Wenbiao] Chinese Academy of Sciences, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Research Center for Human Tissue and Organs DegenerationShenzhen, China.
[Zhang, Feng] The First Affiliated Hospital of Jinan University, Intensive Care UnitGuangzhou, China.
[Xu, Huixuan] Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision MedicineShenzhen, China.
[Hou, Xianliang] Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision MedicineShenzhen, China.
[Tang, Donge] Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision MedicineShenzhen, China.
[Dai, Yong] Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision MedicineShenzhen, China.
RP Chen, W (reprint author), Chinese Academy of Sciences, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Research Center for Human Tissue and Organs Degeneration, Shenzhen, China.
CR Kulik L, El-Serag HB. Epidemiology and Management of Hepatocellular Carcinoma. Gastroenterology, 2019, 156(2):477–91., DOI 10.1053/j.gastro. 2018.08.065
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Hong M, Tao S, Zhang L, Diao LT, Huang X, Huang S, et al. RNA Sequencing: New Technologies and Applications in Cancer Research. J Hematol Oncol, 2020, 13(1):166., DOI 10.1186/s13045-020-01005-x
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Yu H, Bai X, Zheng W. Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma. Dis Markers, 2022, 2022:9124216., DOI 10.1155/2022/9124216
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Wang W, Wei C. Advances in the Early Diagnosis of Hepatocellular Carcinoma. Genes Dis, 2020, 7(3):308–19., DOI 10.1016/j.gendis.2020.01.014
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610199
EP 1610212
DI 10.3389/pore.2022.1610199
PG 14
ER
PT J
AU Amiri, M
Komi, EAD
Vaisi-Raygani, A
Kiani, A
Moradi, M
Aliyari, M
Rahimi, Z
Mohammadi-Noori, E
Bashiri, H
AF Amiri, Mohammad
Komi, Elieh Ali Daniel
Vaisi-Raygani, Asad
Kiani, Amir
Moradi, Mahmoudreza
Aliyari, Mahdieh
Rahimi, Zohreh
Mohammadi-Noori, Ehsan
Bashiri, Homayoon
TI Association Between Vitamin D Binding Protein Gene Polymorphism (rs7041), Vitamin D Receptor, and 25-Hydroxyvitamin D Serum Levels With Prostate Cancer in Kurdish Population in West of Iran
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostate cancer; polymorphism; vitamin D receptor; vitamin D binding protein; 25(OH)-vitamin D
ID prostate cancer; polymorphism; vitamin D receptor; vitamin D binding protein; 25(OH)-vitamin D
AB Prostate cancer (PCa) pathology has been linked to vitamin D, vitamin D receptors (VDRs), and vitamin D binding proteins (VDBPs). We sought to investigate the association between VDR rs2228570 and rs1544410 as well as VDBP rs7041 polymorphisms and serum 25- hydroxyvitamin D (25(OH)-vitamin D) levels in PCa patients. Blood samples were collected from 111 PCa patients and 150 age-matched healthy volunteers. The VDR rs2228570 T/ C, rs1544410 G/A, and VDBP rs7041 T/G genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25(OH)-vitamin D and PSA (Total and Free) serum levels were measured. The frequencies of VDBP genotypes T/G vs. T/T (56.5% vs. 44.5%, p = 0.01) according to the dominant model T/G + G/G vs. T/T (84.3% vs. 71.5%, p = 0.01) were significantly higher in PCa patients when compared to control group and considerably increased the risk of disease by 2.29, 1.44, and 2.13 folds respectively. Interestingly, the results demonstrated that PCa patients with the dominant model (T/G + G/G vs. T/T) of VDBP had significantly lower serum levels of vitamin D and higher serum levels of total and free PSA in comparison to the controls. Furthermore, when compared to controls, PCa patients with the dominant model T allele (T/G + G/G vs. TT) of VDBP had significantly higher vitamin D, total PSA, and free PSA concentrations. Serum levels of 25(OH)-vitamin D and rs7041 T/G polymorphism of the VDBP gene could be potential risk factors for PCa.
C1 [Amiri, Mohammad] Kermanshah University of Medical Sciences, Student Research CommitteeKermanshah, Iran.
[Komi, Elieh Ali Daniel] Kermanshah University of Medical Sciences, Regenerative Medicine Research Center (RMRC)Kermanshah, Iran.
[Vaisi-Raygani, Asad] Kermanshah University of Medical Sciences, Fertility and Infertility Research CenterKermanshah, Iran.
[Kiani, Amir] Kermanshah University of Medical Sciences, Regenerative Medicine Research Center (RMRC)Kermanshah, Iran.
[Moradi, Mahmoudreza] Kermanshah University of Medical Sciences, Regenerative Medicine Research Center (RMRC)Kermanshah, Iran.
[Aliyari, Mahdieh] Kermanshah University of Medical Sciences, Student Research CommitteeKermanshah, Iran.
[Rahimi, Zohreh] Kermanshah University of Medical Sciences, Medical Biology Research CenterKermanshah, Iran.
[Mohammadi-Noori, Ehsan] Kermanshah University of Medical Sciences, Health Institute, Pharmaceutical Sciences Research CenterKermanshah, Iran.
[Bashiri, Homayoon] Kermanshah University of Medical Sciences, Department of Internal MedicineKermanshah, Iran.
RP Bashiri, H (reprint author), Kermanshah University of Medical Sciences, Department of Internal Medicine, Kermanshah, Iran.
EM h.bashiri@kums.ac.ir
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610246
EP 1610253
DI 10.3389/pore.2022.1610246
PG 8
ER
PT J
AU Kothalawala, W
Bartak, B
Nagy, Zs
Zsigrai, S
Szigeti, K
Valcz, G
Takacs, I
Kalmar, A
Molnar, B
AF Kothalawala, J. William
Bartak, K. Barbara
Nagy, B. Zsofia
Zsigrai, Sara
Szigeti, A. Krisztina
Valcz, Gabor
Takacs, Istvan
Kalmar, Alexandra
Molnar, Bela
TI A Detailed Overview About the Single-Cell Analyses of Solid Tumors Focusing on Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE bioinformatics; colorectal cancer; multi-omics; heterogeneity; single-cell sequencing
ID bioinformatics; colorectal cancer; multi-omics; heterogeneity; single-cell sequencing
AB In recent years, the evolution of the molecular biological technical background led to the widespread application of single-cell sequencing, a versatile tool particularly useful in the investigation of tumor heterogeneity. Even 10 years ago the comprehensive characterization of colorectal cancers by The Cancer Genome Atlas was based on measurements of bulk samples. Nowadays, with single-cell approaches, tumor heterogeneity, the tumor microenvironment, and the interplay between tumor cells and their surroundings can be described in unprecedented detail. In this review article we aimed to emphasize the importance of single-cell analyses by presenting tumor heterogeneity and the limitations of conventional investigational approaches, followed by an overview of the whole single-cell analytic workflow from sample isolation to amplification, sequencing and bioinformatic analysis and a review of recent literature regarding the single-cell analysis of colorectal cancers.
C1 [Kothalawala, J. William] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Bartak, K. Barbara] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Nagy, B. Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Zsigrai, Sara] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Szigeti, A. Krisztina] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Valcz, Gabor] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Takacs, Istvan] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Kalmar, Alexandra] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Molnar, Bela] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Kothalawala, W (reprint author), Semmelweis University, Department of Internal Medicine and Oncology, Budapest, Hungary.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610342
EP 1610351
DI 10.3389/pore.2022.1610342
PG 10
ER
PT J
AU Li, G
Liu, D
Flandrin, P
Zhang, Y
Lambert, C
Mallouk, N
Cottier, M
AF Li, Guorong
Liu, Dongdong
Flandrin, Pascale
Zhang, Yang
Lambert, Claude
Mallouk, Nora
Cottier, Michele
TI Tumor-Derived Exosomal RNA From Fine-Needle Aspiration Supernatant as a Novel Liquid Biopsy for Molecular Diagnosis of Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE exosomes; pancreatic adenocarcinoma; liquid biopsy; FNA supernatant; molecular diagnosis; glypican 1
ID exosomes; pancreatic adenocarcinoma; liquid biopsy; FNA supernatant; molecular diagnosis; glypican 1
AB Background: We hypothesized that the fine needle aspiration (FNA) supernatant from tumor might contain tumor-derived exosomes. The objective of this pilot study was to test if tumor-derived exosomal RNA could be found in FNA supernatants for molecular diagnosis of cancer. Methods: 10 FNA samples from pancreatic tumor were included. After the routine recuperation of cellular material by centrifugation, the cell-free Cytolyt liquid was collected instead of being discarded. 10 ml Cytolyt was used to isolate the exosomes. Transmission electronic microscopy (TEM) was used to examine the presence of exosomes. The exosomal marker CD63 was analyzed by flow cytometry. The exosomal RNA was extracted. RT-qPCR was performed to detect the GAPDH and the tumor marker of glypican 1 gene expression. Results: TEM confirmed the presence of exosomes from FNA supernatants. Flow cytometry showed a strong positive expression of exosome marker CD63. The concentration of exosomal RNA ranged from 18.81 to 354.75 ng/μl with an average of 81.76 ng/μl. The average exosomal RNA quantity was 1390.01 ng (range from 319.77 to 6030.75 ng) with an average 260/280 ratio of 2.12. GAPDH was detectable in all samples. Exosomal glypican 1 was detected in all samples of pancreatic ductal adenorcarcinomas (3/3) and absent from benign cystic samples (3/3). Furthermore, exosomal glypican 1 was positive in one sample with a non-contributive cytology and in one sample in which no malignant cell was found. Conclusion: This is the first report that the supernatants from FNA biopsy may contain tumor-derived exosomal RNA. These tumor-derived exosomes from FNA may provide a new liquid biopsy for the molecular diagnosis of cancer.
C1 [Li, Guorong] North Hospital, CHU Saint-Etienne, Department of Digestive Surgery and UrologySaint-Etienne, France.
[Liu, Dongdong] The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Department of Laboratory ScienceGuangzhou, China.
[Flandrin, Pascale] North Hospital, CHU Saint-Etienne, Laboratory of Molecular BiologySaint-Etienne, France.
[Zhang, Yang] Guangzhou HopeTech Biological Technology Co., Ltd.Guangzhou, China.
[Lambert, Claude] North Hospital, CHU Saint- Etienne, Immunology Laboratory, Section of Flow CytometrySaint-Etienne, France.
[Mallouk, Nora] University Jean Monnet, Faculty of Medicine, Center of Electronic Microscopy, CMESSaint-Etienne, France.
[Cottier, Michele] North Hospital, CHU Saint-Etienne, Laboratory of CytopathologySaint-Etienne, France.
RP Li, G (reprint author), North Hospital, CHU Saint-Etienne, Department of Digestive Surgery and Urology, Saint-Etienne, France.
EM grli2001@yahoo.fr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610344
EP 1610349
DI 10.3389/pore.2022.1610344
PG 6
ER
PT J
AU Wang, J
Akter, R
AF Wang, Jie
Akter, Rehana
TI Cancer-Associated Stromal Fibroblast-Derived Transcriptomes Predict Poor Clinical Outcomes and Immunosuppression in Colon Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colon cancer; survival time; immunosuppressive roles; metastatic scores; cancer-associated fibroblasts
ID colon cancer; survival time; immunosuppressive roles; metastatic scores; cancer-associated fibroblasts
AB Background: Previous studies revealed that colonic cancer-associated fibroblasts (CAFs) are associated with the modulation of the colon tumor microenvironment (TME). However, identification of key transcriptomes and their correlations with the survival prognosis, immunosuppression, tumor progression, and metastasis in colon cancer remains lacking. Methods: We used the GSE46824, GSE70468, GSE17536, GSE35602, and the cancer genome atlas (TCGA) colon adenocarcinoma (COAD) datasets for this study.We identified the differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, hub genes, and survival-associated genes in colon cancer. Finally, we investigated the correlation of key genes with the survival prognosis, immunosuppression, and metastasis. Results: We identified 246 common DEGs between the GSE46824 and GSE70468 datasets of colonic CAFs, which included 72 upregulated and 174 downregulated genes. The upregulated pathways are mainly involved with cancers and cellular signaling, and downregulated pathways are involvedwith immune regulation and cellular metabolism. The search tool for the retrieval of interacting genes (STRING)-based analysis identified 15 hub genes and 9 significant clusters in colonic CAFs. The upregulation of CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 and downregulation of FBN2 are correlated with a shorter survival time in colon cancer. The CTHRC1, PDGFC, PDLIM3, and NTM genes are positively correlated with the infiltration of tumor-associated macrophages (TAM), macrophages, M2 macrophages, the regulatory T cells (Tregs), T cell exhaustion, and myeloid-derived suppressor cells (MDSCs), indicating the immunosuppressive roles of these transcriptomes in colon cancer. Moreover, the CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 genes are gradually increased from normal tissue to the tumor and tumor to the metastatic tumor, and FBN2 showed the reverse pattern. Furthermore, the CTHRC1, FBN2, PDGFC, PDLIM3, and NTM genes are positively correlated with the metastatic scores in colon cancer. Then, we revealed that the expression value of CTHRC1, FBN2, PDGFC, PDLIM3, NTM, and SLC16A3 showed the diagnostic efficacy in colonic CAFs. Finally, the expression level of CTHRC1, PDGFC, and NTM genes are consistently altered in colon tumor stroma as well as in the higher CAFs-group of TCGA COAD patients. Conclusion: The identified colonic CAFs-derived key genes are positively correlated with survival prognosis, immunosuppression, tumor progression, and metastasis.
C1 [Wang, Jie] First Affiliated Hospital of Xinjiang Medical University, Department of PharmacyUrumqi, China.
[Akter, Rehana] Center for Research Innovation and Development (CRID), Bioinformatics Research Lab.Dhaka, Bangladesh.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610350
EP 1610365
DI 10.3389/pore.2022.1610350
PG 16
ER
PT J
AU Han, D
Cho, SE
Park, J
Kim, D
AF Han, Dawool
Cho, Sandra Eunae
Park, Jiho
Kim, Dongwook
TI Case Report: Papillary Lesions at the Mouth Floor May Mimic Sialadenoma Papilliferum
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE salivary gland; tumor; sialadenoma papilliferum; oral pathology; papillary lesion; oral cavity; oromaxillofacial
ID salivary gland; tumor; sialadenoma papilliferum; oral pathology; papillary lesion; oral cavity; oromaxillofacial
AB Salivary gland tumor Sialadenoma papilliferum (SialP) clinically resembles papillary epithelial lesions, such as squamous papilloma (SqP) or verrucous leukoplakia. Pathological sampling including an adequate depth of both the mucosa and submucosa layer is required for discrimination between the diseases. Though ductal proliferation in the submucosa is characteristic in SialP, papillary lesions arising at the mouth floor, specifically near the ductal orifice, are more problematic. Salivary gland ductal ectasia, along with the overlying papillary hyperplasia, may mimic the biphasic tumorous growth pattern of SialP, making discrimination extremely difficult. Further cellular dysplasia in the papillary mucosal lesion raises the possibility of malignant transformation in a known benign lesion, SialP. Herein, we present a case of SqP at the mouth floor which mimicked both clinical and pathological features of SialP and compared it with a definite case of SialP. Moreover, we discuss major differential points that clinicians and pathologists should consider during diagnosis of oral papillary lesions arising near the salivary glands.
C1 [Han, Dawool] Yonsei University College of Dentistry, Oral Cancer Research Institute, Department of Oral PathologySeoul, South Korea.
[Cho, Sandra Eunae] Yonsei University College of Dentistry, Oral Cancer Research Institute, Department of Oral PathologySeoul, South Korea.
[Park, Jiho] Yonsei University College of Dentistry, Department of Oral and Maxillofacial SurgerySeoul, South Korea.
[Kim, Dongwook] Yonsei University College of Dentistry, Department of Oral and Maxillofacial SurgerySeoul, South Korea.
RP Kim, D (reprint author), Yonsei University College of Dentistry, Department of Oral and Maxillofacial Surgery, Seoul, South Korea.
EM dwkimomfs@yuhs.ac
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610352
EP 1610359
DI 10.3389/pore.2022.1610352
PG 8
ER
PT J
AU Wang, H
Miao, J
Wen, Y
Xia, X
Chen, Y
Huang, M
Chen, Sh
Zhao, Z
Zhang, Y
Chen, Ch
Zhu, X
AF Wang, Hao
Miao, Ji
Wen, Yazhou
Xia, Xihua
Chen, Yanan
Huang, Mengli
Chen, Shiqing
Zhao, Zhengyi
Zhang, Yuzi
Chen, Chunzhu
Zhu, Xinhua
TI Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE next-generation sequencing; TMB; ERBB2; solid tumors; anti-HER2 agents
ID next-generation sequencing; TMB; ERBB2; solid tumors; anti-HER2 agents
AB ERBB2 abnormalities frequently occur and serve as rationale therapeutic targets in cancer. In this study, clinical and next-generation sequencing data from 14,956 patients across more than 20 tumor types were collected. A total of 406 (2.7%) patients were identified with ERBB2 amplifications, and 303 (2.0%) patients with pathogenic somatic ERBB2 mutations. ERBB2 amplifications fell most frequently in breast (15.9%) and stomach (8.3%) cancers. Somatic ERBB2 SNVs/indels occurred most common in bladder/urinary tract (7.3%) and intestine (6.1%) cancers. The top mutated ERBB2 SNVs/indels were p.Y772_A775dup (25.5%) and p.S310F/Y (19.9%). Significantly higher rates of ERBB2 SNV/indels were found in women compared to men (2.8% vs. 1.5%, p < 0.0001). CDK12 was the most common co-amplification gene with ERBB2 in cancers with a high frequency of ERBB2 amplifications. Patients with ERBB2 amplifications or mutations had higher TMB compared with patients with non-ERBB2 alterations. The study provided the landscape of ERBB2 alterations across a variety of solid tumors that may benefit fromanti-HER2 agents.
C1 [Wang, Hao] The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Department of General SurgeryNanjing, China.
[Miao, Ji] The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Department of General SurgeryNanjing, China.
[Wen, Yazhou] Nanjing Maternity and Child Health Care Hospital, Women’s Hospital of Nanjing Medical University, Department of AnesthesiologyNanjing, China.
[Xia, Xihua] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Chen, Yanan] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Huang, Mengli] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Chen, Shiqing] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhao, Zhengyi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhang, Yuzi] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Chen, Chunzhu] 3D Medicines Inc., The Medical DepartmentShanghai, China.
[Zhu, Xinhua] The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Department of General SurgeryNanjing, China.
RP Zhu, X (reprint author), The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Department of General Surgery, Nanjing, China.
EM drzhuxh@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610360
EP 1610367
DI 10.3389/pore.2022.1610360
PG 8
ER
PT J
AU Rubovszky, G
Kocsis, J
Boer, K
Chilingirova, N
Dank, M
Kahan, Zs
Kaidarova, D
Kover, E
Vertakova Krakovska, B
Mahr, K
Mrinakova, B
Piko, B
Bozovic-Spasojevic, I
Horvath, Zs
AF Rubovszky, Gabor
Kocsis, Judit
Boer, Katalin
Chilingirova, Nataliya
Dank, Magdolna
Kahan, Zsuzsanna
Kaidarova, Dilyara
Kover, Erika
Vertakova Krakovska, Bibiana
Mahr, Karoly
Mrinakova, Bela
Piko, Bela
Bozovic-Spasojevic, Ivana
Horvath, Zsolt
TI Systemic Treatment of Breast Cancer. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Guideline
DE early breast cancer; locally advanced breast cancer; adjuvant treatment; neoadjuvant treatment; metastatic breast cancer; inflammatory breast cancer; guideline
ID early breast cancer; locally advanced breast cancer; adjuvant treatment; neoadjuvant treatment; metastatic breast cancer; inflammatory breast cancer; guideline
AB This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified based on the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The professional guideline primarily reflects the resolutions and recommendations of the current ESMO, NCCN and ABC5, as well as that of the St. Gallen Consensus Conference statements. The recommendations cover classical prognostic factors and certain multigene tests, which play an important role in therapeutic decision-making. From a didactic point of view, the text first addresses early and then locally advanced breast cancer, followed by locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to the available therapeutic options. At the end of the recommendations, we summarize the criteria for treatment in certain rare clinical situations.
C1 [Rubovszky, Gabor] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai OsztalyBudapest, Hungary.
[Kocsis, Judit] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Boer, Katalin] St. Margit Hospital, Clinical Oncology DepartmentBudapest, Hungary.
[Chilingirova, Nataliya] Medical University-Pleven, Heart and Brain Hospital, Science and Research Institute, Clinic Center of ExcellencePleven, Bulgaria.
[Dank, Magdolna] Semmelweis University, Department of OncologyBudapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Kaidarova, Dilyara] Kazakh Institute of Oncology and RadiologyAlmaty, Kazakhstan.
[Kover, Erika] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Vertakova Krakovska, Bibiana] Comenius University, Faculty of Medicine, 1st Department of OncologyBratislava, Slovakia.
[Mahr, Karoly] Zala Megyei Szent Rafael Korhaz, OnkologiaZalaegerszeg, Hungary.
[Mrinakova, Bela] Comenius University, Faculty of Medicine, 1st Department of OncologyBratislava, Slovakia.
[Piko, Bela] Bekes Megyei Kozponti Korhaz, Pandy Kalman Tagkorhaz, Megyei Onkologiai CentrumGyula, Hungary.
[Bozovic-Spasojevic, Ivana] Daily Chemotherapy Hospital, Institute for Oncology and Radiology of SerbiaBelgrade, Serbia.
[Horvath, Zsolt] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
RP Rubovszky, G (reprint author), Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai Osztaly, Budapest, Hungary.
EM rubovszkyg@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610383
EP 1610408
DI 10.3389/pore.2022.1610383
PG 26
ER
PT J
AU Liang, L
Chai, Y
Chai, F
Liu, H
Ma, N
Zhang, H
Zhang, Sh
Nong, L
Li, T
Zhang, B
AF Liang, Li
Chai, Yijie
Chai, Fei
Liu, Haijing
Ma, Ningning
Zhang, Hong
Zhang, Shuang
Nong, Lin
Li, Ting
Zhang, Bo
TI Expression of SASP, DNA Damage Response, and Cell Proliferation Factors in Early Gastric Neoplastic Lesions: Correlations and Clinical Significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; gastric cancer; p53; DNA damage response; endoscopic submucosal dissection; senescence-associated secretory phenotype
ID immunohistochemistry; gastric cancer; p53; DNA damage response; endoscopic submucosal dissection; senescence-associated secretory phenotype
AB The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated senescence-associated secretory phenotype (SASP) pathway has recently been identified in the suppression and promotion of cancers. However, its practical role in carcinogenesis remains to be comprehensively elucidated. Here, we describe an investigation analysing SASP activity and its correlations with DNA damage response (DDR), genomic mutations, and cell proliferation in gastric carcinogenesis among 30 cases with available endoscopic submucosal dissection (ESD) specimens of early neoplastic lesions (including low-grade dysplasia [LGD], high-grade dysplasia [HGD], and intramucosal carcinoma). The positive cells of senescence-associated β- galactosidase staining and cGAS, STING, interferon-regulatory factor 3 (IRF3), and signal transducer and activator of transcription 6 (STAT6) expression levels using immunostaining were elevated in HGD and in cancers. Similarly, increased expression of the Fanconi anemia group D2 (FANCD2) protein, tumour suppressor p53 binding protein 1 (TP53BP1), and replication protein A (RPA2) (i.e., primary DDR factors) was detected in HGD and in cancers; these increased expression levels were closely correlated with high expression of Ki67 and minichromosome maintenance complex component 7 (MCM7) proteins. Moreover, genomic mutations in TP53 gene were detected in 56.67% of the evaluated cases (17/30) using next-generation sequencing, and positive staining was verified in HGD and in cancers. Statistical analysis revealed that cell proliferation closely correlated with the expression of DDR factors, of which TP53BP1 was positively associated with SASP factors and IRF3 was positively correlated with cell proliferation. In addition, an analysis evaluating clinical features demonstrated that STAT6-positive cases showed a longer progression-free survival time than STAT6-negative cases. Our evaluation, conducted using a limited number of specimens, suggests SASP may be prevalent in early gastric neoplastic lesions and could be activated by accelerated cell proliferation-induced DDR. The clinical significance of SASP still needs to be determined.
C1 [Liang, Li] Peking University First Hospital, Department of PathologyBeijing, China.
[Chai, Yijie] Health Science Center, Peking University, Department of PathologyBeijing, China.
[Chai, Fei] Shanxi Medical University, Fenyang College, Department of PathologyFenyang, China.
[Liu, Haijing] Health Science Center, Peking University, Department of PathologyBeijing, China.
[Ma, Ningning] Health Science Center, Peking University, Department of PathologyBeijing, China.
[Zhang, Hong] Peking University First Hospital, Department of PathologyBeijing, China.
[Zhang, Shuang] Peking University First Hospital, Department of PathologyBeijing, China.
[Nong, Lin] Peking University First Hospital, Department of PathologyBeijing, China.
[Li, Ting] Peking University First Hospital, Department of PathologyBeijing, China.
[Zhang, Bo] Health Science Center, Peking University, Department of PathologyBeijing, China.
RP Zhang, B (reprint author), Health Science Center, Peking University, Department of Pathology, Beijing, China.
EM 13601150230@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610401
EP 1610413
DI 10.3389/pore.2022.1610401
PG 13
ER
PT J
AU Hu, J
Yang, J
Chen, L
Meng, X
Zhang, X
Li, W
Li, Z
Huang, G
AF Hu, Jinxian
Yang, Jihu
Chen, Lei
Meng, Xiangbao
Zhang, Xiejun
Li, Weiping
Li, Zongyang
Huang, Guodong
TI Alterations of the Gut Microbiome in Patients With Pituitary Adenoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pituitary adenoma; invasive pituitary adenoma; gut microbiome; metagenome sequencing; noninvasive pituitary adenoma
ID pituitary adenoma; invasive pituitary adenoma; gut microbiome; metagenome sequencing; noninvasive pituitary adenoma
AB Pituitary adenoma (PA) includes invasive pituitary adenoma (IPA) and noninvasive pituitary adenoma (NIPA), which are associated with the endocrine system. The gut microbiome plays an important role in human metabolism, but the association between the gut microbiome and pituitary adenoma remains unclear. A total of 44 subjects were enrolled in this study. Of these, 29 PA patients were further divided into IPA patients (n = 13) and NIPA patients (n = 16), while 15 healthy age-matched subjects were defined as control subjects. We collected faecal samples and characterized the gut microbial profiles by metagenomic sequencing using the Illumina X-ten platform. PLS-DA showed different microbial clusters among the three groups, and slightly different microbial ecological networks were observed. LEfSe analysis revealed significant alterations in the microbial community among PA patients. In particular, the enrichment of Clostridium innocuum, along with the reduced abundance of Oscillibacter sp. 57_20 and Fusobacterium mortiferum, were observed both in the IPA and NIPA groups compared to the control group. Moreover, PA patients could be effectively classified based on these bacteria using a support vector machine algorithm. In summary, this study demonstrated significant differences in the gut microbiome between PA patients and healthy controls. Future mechanistic experiments are needed to determine whether such alterations are a cause or consequence of pituitary adenoma.
C1 [Hu, Jinxian] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Yang, Jihu] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Chen, Lei] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Meng, Xiangbao] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Zhang, Xiejun] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Li, Weiping] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Li, Zongyang] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
[Huang, Guodong] The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of NeurosurgeryShenzhen, China.
RP Huang, G (reprint author), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Key Laboratory of Neurosurgery, Inst Translat Med, Department of Neurosurgery, Shenzhen, China.
EM huangguodong@email.szu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610402
EP 1610409
DI 10.3389/pore.2022.1610402
PG 8
ER
PT J
AU Liang, ZQ
He, RQ
Luo, JY
Huang, ZG
Li, J
Zhong, LY
Chen, JH
Huang, SN
Shi, L
Wei, KL
Zeng, JH
Zeng, JJ
Chen, G
AF Liang, Zi-Qian
He, Rong-Quan
Luo, Jia-Yuan
Huang, Zhi-Guang
Li, Jie
Zhong, Lu-Yang
Chen, Jun-Hong
Huang, Su-Ning
Shi, Lin
Wei, Kang-Lai
Zeng, Jiang-Hui
Zeng, Jing-Jing
Chen, Gang
TI Downregulated Dual-Specificity Protein Phosphatase 1 in Ovarian Carcinoma: A Comprehensive Study With Multiple Methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE molecular docking; dual-specificity protein phosphatase 1; immune landscape; cancer associated fibroblasts; ovarian carcinoma
ID molecular docking; dual-specificity protein phosphatase 1; immune landscape; cancer associated fibroblasts; ovarian carcinoma
AB Introduction: We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Materials and Methods: Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) fromeach cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. Results: A pooled SMD of −1.19 (95% CI [−2.00, −0.38], p = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. Conclusion: DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways.
C1 [Liang, Zi-Qian] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[He, Rong-Quan] The First Affiliated Hospital of Guangxi Medical University, Department of Medical OncologyNanning, China.
[Luo, Jia-Yuan] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Huang, Zhi-Guang] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Li, Jie] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Zhong, Lu-Yang] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Chen, Jun-Hong] Guangxi Maternal and Child Health Hospital, Department of PathologyNanning, China.
[Huang, Su-Ning] Guangxi Medical University Cancer Hospital, Department of RadiotherapyNanning, China.
[Shi, Lin] The Second Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Wei, Kang-Lai] The Second Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Zeng, Jiang-Hui] The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People’s Hospital, Department of Clinical LaboratoryNanning, China.
[Zeng, Jing-Jing] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
[Chen, Gang] The First Affiliated Hospital of Guangxi Medical University, Department of PathologyNanning, China.
RP Chen, G (reprint author), The First Affiliated Hospital of Guangxi Medical University, Department of Pathology, Nanning, China.
EM chengang@gxmu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610404
EP 1610418
DI 10.3389/pore.2022.1610404
PG 15
ER
PT J
AU Zhou, J
Lai, M
Ni, Y
Li, Sh
Zhen, J
Du, F
Zhang, X
Song, Ch
Cai, L
AF Zhou, Jiangfen
Lai, Mingyao
Ni, Yang
Li, Shaoqun
Zhen, Junjie
Du, Furong
Zhang, Xing
Song, Chao
Cai, Linbo
TI Case Report: Clinicopathological and Genetic Features of IDH-Mutant Brainstem Glioma in Adults: Report of Five Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE prognosis; IDH1 mutation; molecular features; temozolomide; brainstem glioma
ID prognosis; IDH1 mutation; molecular features; temozolomide; brainstem glioma
AB Adult brainstem gliomas are rare central nervous system tumors that represent a heterogeneous group of tumors. Somatic IDH mutations are uncommon in adult brainstem gliomas and there are few relevant clinical studies. Here, we reported five patients with IDH1 mutations associated with brainstem gliomas, including four cases of IDH1 R132H mutations and one case of R132G mutation. All patients were treated with focal intensity-modulated radiation therapy (IMRT) with concurrent temozolomide (TMZ). One patient died, one relapsed, and three survived to date. All these cases carried a pathogenic variant of TP53, among whom 1 harbored ATRX mutation and 1 had H3K27M mutation. Moreover, we also found some genes related to a worse prognosis, such as CDK4/6 amplification. These findings demonstrate that the specific characteristics of IDHmutant brainstem gliomas should be considered in diagnostic workflows to make therapeutic regimens and improve the prognosis.
C1 [Zhou, Jiangfen] Guangdong Sanjiu Brain Hospital, Department of Neuro-OncologyGuangzhou, China.
[Lai, Mingyao] Guangdong Sanjiu Brain Hospital, Department of Neuro-OncologyGuangzhou, China.
[Ni, Yang] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Translational Medicine and Innovative Drug DevelopmentNanjing, China.
[Li, Shaoqun] Guangdong Sanjiu Brain Hospital, Department of Neuro-OncologyGuangzhou, China.
[Zhen, Junjie] Guangdong Sanjiu Brain Hospital, Department of Neuro-OncologyGuangzhou, China.
[Du, Furong] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Translational Medicine and Innovative Drug DevelopmentNanjing, China.
[Zhang, Xing] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Translational Medicine and Innovative Drug DevelopmentNanjing, China.
[Song, Chao] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Translational Medicine and Innovative Drug DevelopmentNanjing, China.
[Cai, Linbo] Guangdong Sanjiu Brain Hospital, Department of Neuro-OncologyGuangzhou, China.
RP Cai, L (reprint author), Guangdong Sanjiu Brain Hospital, Department of Neuro-Oncology, Guangzhou, China.
EM cailinbogz@126.com
CR Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol, 2015, 17(Suppl. 4):iv1–iv62., DOI 10.1093/neuonc/nov189
Eisele SC, Reardon DA. Adult Brainstem Gliomas. Cancer, 2016, 122: 2799–809., DOI 10.1002/cncr.29920
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Johnson DR, Brown PD, Galanis E, Hammack JE. Pilocytic Astrocytoma Survival in Adults: Analysis of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. J Neurooncol, 2012, 108:187–93., DOI 10.1007/s11060-012-0829-0
Wang Y, Wang L, Blumcke I, Zhang W, Fu Y, Shan Y, et al. Integrated Genotype-Phenotype Analysis of Long-Term Epilepsy-Associated Ganglioglioma. Brain Pathol, 2022, 32:e13011., DOI 10.1111/bpa.13011
Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, et al. Type and Frequency of IDH1 and IDH2 Mutations Are Related to Astrocytic and Oligodendroglial Differentiation and Age: a Study of 1, 010 Diffuse Gliomas. Acta Neuropathol, 2009, 118:469–74., DOI 10.1007/s00401-009-0561-9
Carlos-Escalante JA, Gomez-Flores-Ramos L, Bian X, Perdomo-Pantoja A, de Andrade KC, Mejia-Perez SI, et al. Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma. Cell Mol Neurobiol, 2021, 41:1285–97., DOI 10.1007/s10571-020-00901-7
Wang Z, Rajaraman P, Melin BS, Chung CC, Zhang W, McKean-Cowdin R, et al. Further Confirmation of Germline Glioma Risk Variant Rs78378222 in TP53 and its Implication in Tumor Tissues via Integrative Analysis of TCGA Data. Hum Mutat, 2015, 36:684–8., DOI 10.1002/humu.22799
Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, et al. Prognostic Relevance of Genetic Alterations in Diffuse Lower-Grade Gliomas. Neuro Oncol, 2018, 20:66–77., DOI 10.1093/neuonc/nox132
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Barrow Neurological Institute. A Phase 0/II Study of Ribociclib, LEE011, in Combination with Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection. Available online: https://ClinicalTrials.gov/ show/NCT03834740, Accessed May 16, 2020).
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Wiestler B, Capper D, Holland-Letz T, Korshunov A, von Deimling A, Pfister SM, et al. ATRX Loss Refines the Classification of Anaplastic Gliomas and Identifies a Subgroup of IDH Mutant Astrocytic Tumors with Better Prognosis. Acta Neuropathol, 2013, 126:443–51., DOI 10.1007/s00401-013-1156-z
Richardson TE, Sathe AA, Kanchwala M, Jia G, Habib AA, Xiao G, et al. Genetic and Epigenetic Features of Rapidly Progressing IDH-Mutant Astrocytomas. J Neuropathol Exp Neurol, 2018, 77:542–8., DOI 10.1093/jnen/nly026
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610408
EP 1610412
DI 10.3389/pore.2022.1610408
PG 5
ER
PT J
AU Kontsek, E
Pesti, A
Gordon, P
Tornoczki, T
Smuk, G
Gergely, Sz
Kiss, A
AF Kontsek, Endre
Pesti, Adrian
Gordon, Peter
Tornoczki, Tamas
Smuk, Gabor
Gergely, Szilveszter
Kiss, Andras
TI Mid-Infrared Imaging Characterization to Differentiate Lung Cancer Subtypes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; fingerprint region; transflectance; SVM; LDA; FTIR; infrared
ID lung cancer; fingerprint region; transflectance; SVM; LDA; FTIR; infrared
AB Introduction: Lung cancer is the most common malignancy worldwide. Squamous cell carcinoma (SQ) and adenocarcinoma (LUAD) are the two most frequent histological subtypes. Small cell carcinoma (SCLC) subtype has the worst prognosis. Differential diagnosis is essential for proper oncological treatment. Life science associated mid- and near-infrared based microscopic techniques have been developed exponentially, especially in the past decade. Vibrational spectroscopy is a potential non-destructive approach to investigate malignancies. Aims: Our goal was to differentiate lung cancer subtypes by their label-free mid-infrared spectra using supervised multivariate analyses. Material and Methods: Formalin-fixed paraffin-embedded (FFPE) samples were selected from the archives. Three subtypes were selected for each group: 10- 10 cases SQ, LUAD and SCLC. 2 μm thick sections were cut and laid on aluminium coated glass slides. Transflection optical setup was applied on Perkin-Elmer infrared microscope. 250 × 600 μm areas were imaged and the so-called mid-infrared fingerprint region (1800-648cm−1) was further analysed with linear discriminant analysis (LDA) and support vector machine (SVM) methods. Results: Both “patient-based” and “pixel-based” approaches were examined. Patientbased analysis by using 3 LDA models and 2 SVM models resulted in different separations. The higher the cut-off value the lower is the accuracy. The linear C-support vector classification (C-SVC) SVM resulted in the best (100%) accuracy for the three subtypes using a 50% cut-off value. The pixel-based analysis gave, similarly, the linear C-SVC SVM model to be the most efficient in the statistical indicators (SQ sensitivity 81.65%, LUAD sensitivity 82.89% and SCLC sensitivity 88.89%). The spectra cut-off, the kernel function and the algorithm function influence the accuracy. Conclusion: Mid-Infrared imaging could be used to differentiate FFPE lung cancer subtypes. Supervised multivariate tools are promising to accurately separate lung tumor subtypes. The long-term perspective is to develop a spectroscopy-based diagnostic tool, revolutionizing medical differential diagnostics, especially cancer identification.
C1 [Kontsek, Endre] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Pesti, Adrian] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Gordon, Peter] Budapest University of Technology and Economics, Department of Electronics TechnologyBudapest, Hungary.
[Tornoczki, Tamas] University of Pecs, Department of PathologyPecs, Hungary.
[Smuk, Gabor] University of Pecs, Department of PathologyPecs, Hungary.
[Gergely, Szilveszter] Budapest University of Technology and Economics, Department of Applied Biotechnology and Food ScienceBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kontsek, E (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM kontsek.endre@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610439
EP 1610446
DI 10.3389/pore.2022.1610439
PG 8
ER
PT J
AU Truszkowska, E
Andrzejewska, M
Szymanska, C
Wziatek, A
Derwich, K
AF Truszkowska, Ewelina
Andrzejewska, Marta
Szymanska, Cyntia
Wziatek, Agnieszka
Derwich, Katarzyna
TI Case Report: Brentuximab Vedotin Associated Acute Pancreatitis in a Pediatric Hodgkin Lymphoma Patient: Case Report and Literature Review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Hodgkin lymphoma; pediatric oncology; brentuximab vedotin; acute pancreatitis; side effects
ID Hodgkin lymphoma; pediatric oncology; brentuximab vedotin; acute pancreatitis; side effects
AB Brentuximab vedotin is a conjugate drug used mainly in Hodgkin lymphoma, systemic and primary cutaneous anaplastic large cell lymphomas, and CD30-expressing peripheral T-cell lymphoma. We report a unique case of acute pancreatitis associated with brentuximab vedotin in a 17-year-old male patient suffering from classical Hodgkin lymphoma. Diagnosed in 2020, the patient was classified to an intermediate therapeutic group and disease’s grade was IIIAE. The patient was treated with brentuximab vedotin and bendamustine in the third line. Two weeks after the drug administration, the patient developed acute epigastric pain. Laboratory and radiological findings confirmed the clinical suspicion of acute pancreatitis that was managed with opioid pain medications, meropenem, parenteral nutrition, ondansetron and omeprazole. This is the first case report of brentuximab vedotin-associated acute pancreatitis in the pediatric patient reported in the literature to the best of our knowledge.
C1 [Truszkowska, Ewelina] Poznan University of Medical Sciences, Faculty of MedicinePoznan, Poland.
[Andrzejewska, Marta] Poznan University of Medical Sciences, Faculty of MedicinePoznan, Poland.
[Szymanska, Cyntia] Poznan University of Medical Sciences, Faculty of MedicinePoznan, Poland.
[Wziatek, Agnieszka] Poznan University of Medical Sciences, Institute of Pediatrics, Department of Pediatric Oncology, Hematology and TransplantologyPoznan, Poland.
[Derwich, Katarzyna] Poznan University of Medical Sciences, Institute of Pediatrics, Department of Pediatric Oncology, Hematology and TransplantologyPoznan, Poland.
RP Derwich, K (reprint author), Poznan University of Medical Sciences, Institute of Pediatrics, Department of Pediatric Oncology, Hematology and Transplantology, Poznan, Poland.
EM kderwich@ump.edu.pl
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610445
EP 1610451
DI 10.3389/pore.2022.1610445
PG 7
ER
PT J
AU Kawasaki, Y
Suzuki, H
Suzuki, Sh
Yamada, T
Suzuki, M
Ito, A
Hatakeyama, H
Miura, M
Omori, Y
AF Kawasaki, Yohei
Suzuki, Hitomi
Suzuki, Shinsuke
Yamada, Takechiyo
Suzuki, Maya
Ito, Ayumi
Hatakeyama, Haruka
Miura, Masahito
Omori, Yasufumi
TI GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma —Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epithelial-mesenchymal transition; cancer stem cells; radiotherapy; head and neck squamous cell carcinoma; glycoprotein nonmetastatic melanoma protein B; prognostic factor
ID epithelial-mesenchymal transition; cancer stem cells; radiotherapy; head and neck squamous cell carcinoma; glycoprotein nonmetastatic melanoma protein B; prognostic factor
AB Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens. Methods: We examined the sphere formation, invasion, and migration ability of GPNMBpositive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival. Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor. Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.
C1 [Kawasaki, Yohei] Akita University Graduate School of Medicine, Department of Otorhinolaryngology and Head-and-Neck SurgeryAkita, Japan.
[Suzuki, Hitomi] Akita University Graduate School of Medicine, Department of Otorhinolaryngology and Head-and-Neck SurgeryAkita, Japan.
[Suzuki, Shinsuke] Akita University Graduate School of Medicine, Department of Otorhinolaryngology and Head-and-Neck SurgeryAkita, Japan.
[Yamada, Takechiyo] Akita University Graduate School of Medicine, Department of Otorhinolaryngology and Head-and-Neck SurgeryAkita, Japan.
[Suzuki, Maya] Akita University Graduate School of Medicine, Department of Molecular and Tumour PathologyAkita, Japan.
[Ito, Ayumi] Akita University Graduate School of Medicine, Department of Molecular and Tumour PathologyAkita, Japan.
[Hatakeyama, Haruka] Akita University Graduate School of Medicine, Department of Molecular and Tumour PathologyAkita, Japan.
[Miura, Masahito] Akita University Graduate School of Medicine, Department of Molecular and Tumour PathologyAkita, Japan.
[Omori, Yasufumi] Akita University Graduate School of Medicine, Department of Molecular and Tumour PathologyAkita, Japan.
RP Omori, Y (reprint author), Akita University Graduate School of Medicine, Department of Molecular and Tumour Pathology, Akita, Japan.
EM yasu@med.akita-u.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610450
EP 1610462
DI 10.3389/pore.2022.1610450
PG 13
ER
PT J
AU Xie, Y
Wu, H
Hu, W
Zhang, H
Li, A
Zhang, Z
Ren, Sh
Zhang, X
AF Xie, Yuning
Wu, Hongjiao
Hu, Wenqian
Zhang, Hongmei
Li, Ang
Zhang, Zhi
Ren, Shuhua
Zhang, Xuemei
TI Identification of Hub Genes of Lung Adenocarcinoma Based on Weighted Gene Co-Expression Network in Chinese Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE next-generation sequencing; survival analysis; lung adenocarcinoma; WGCNA; PPI network
ID next-generation sequencing; survival analysis; lung adenocarcinoma; WGCNA; PPI network
AB Purpose: Lung adenocarcinoma is one of the most common malignancies. Though some historic breakthroughs have been made in lung adenocarcinoma, its molecular mechanisms of development remain elusive. The aim of this study was to identify the potential genes associated with the lung adenocarcinoma progression and to provide new ideas for the prognosis evaluation of lung adenocarcinoma. Methods: The transcriptional profiles of ten pairs of snap-frozen tumor and adjacent normal lung tissues were obtained by performing RNA-seq. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks in order to explore the associations of gene sets with the clinical features and to investigate the functional enrichment analysis of co-expression genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment Analysis (GSEA) analyses were performed using clusterProfiler. The protein-protein network (PPI) was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and hub genes were identified using Cytohubba in Cytoscape. Transcription factor enrichment analysis was performed by the RcisTarget program in R language. Results: Based on RNA-seq data, 1,545 differentially expressed genes (DEGs) were found. Eight co-expression modules were identified among these DEGs. The blue module exhibited a strong correlation with LUAD, in which ADCY4, RXFP1, AVPR2, CALCRL, ADRB1, RAMP3, RAMP2 and VIPR1 were hub genes. A low expression level of RXFP1, AVPR2, ADRB1 and VIPR1 was detrimental to the survival of LUAD patients. Genes in the blue module enriched in 86 Gene Ontology terms and five KEGG pathways. We also found that transcription factors EGR3 and EXOSC3 were related to the biological function of the blue module. Overall, this study brings a new perspective to the understanding of LUAD and provides possible molecular biomarkers for prognosis evaluation of LUAD.
C1 [Xie, Yuning] North China University of Science and Technology, School of Public HealthTangshan, China.
[Wu, Hongjiao] North China University of Science and Technology, School of Public HealthTangshan, China.
[Hu, Wenqian] North China University of Science and Technology, School of Public HealthTangshan, China.
[Zhang, Hongmei] North China University of Science and Technology, School of Public HealthTangshan, China.
[Li, Ang] North China University of Science and Technology, School of Public HealthTangshan, China.
[Zhang, Zhi] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
[Ren, Shuhua] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
[Zhang, Xuemei] North China University of Science and Technology, School of Public HealthTangshan, China.
RP Zhang, X (reprint author), North China University of Science and Technology, School of Public Health, Tangshan, China.
EM jyxuemei@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610455
EP 1610465
DI 10.3389/pore.2022.1610455
PG 11
ER
PT J
AU Liu, J
Liu, L
Su, Y
Wang, Y
Zhu, Y
Sun, X
Guo, Y
Shan, J
AF Liu, Jia
Liu, Lei
Su, Yang
Wang, Yi
Zhu, Yuchun
Sun, Xiaobin
Guo, Yuanbiao
Shan, Jing
TI IL-33 Participates in the Development of Esophageal Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE EMT; esophageal adenocarcinoma; interleukin-33; ST2; EAC rat model
ID EMT; esophageal adenocarcinoma; interleukin-33; ST2; EAC rat model
AB Background: The progression from chronic gastroesophageal reflux disease (GERD) to Barrett esophagus (BE) and esophageal adenocarcinoma (EAC) is an inflammatory-driven neoplastic change. Interleukin-33 (IL-33) has identified as a crucial factor in several inflammatory disorders and malignancies. Methods: The high-density tissue microarray of the human EAC was analyzed with IL-33 immunohistochemistry staining (IHC). By anastomosing the jejunum with the esophagus, the rat model of EAC with mixed gastroduodenal reflux was established. The expression of IL-33 was determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blot (WB), IHC and enzyme-linked immunosorbent assay (ELISA). Esophageal adenocarcinoma cells (OE19 and OE33) and human esophageal epithelial cells (HEECs) were used. Results: In the cytoplasm of human EAC tissue, IL-33 expression was substantially greater than in adjacent normal tissue. In rat model, the expression of IL-33 in the EAC group was considerably greater than in the control group, and this expression increased with the upgrade of pathological stage. In in vitro experiment, the mRNA and protein levels of IL-33 were considerably greater in OE19 and OE33 than in HEECs. The stimulation of IL- 33 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of OE19 and OE33, but soluble ST2 (sST2) inhibited these effects. IL-33 stimulated the release of IL-6 by OE19 and OE33 cells. Conclusion: This study demonstrated the overexpression of IL-33 in the transition from GERD to EAC and that IL-33 promoted carcinogenesis in EAC cells through ST2. IL-33 might be a possible preventive target for EAC.
C1 [Liu, Jia] Southwest Jiaotong University, School of MedicineChengdu, China.
[Liu, Lei] The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Medical Research CenterChengdu, China.
[Su, Yang] Southwest Jiaotong University, School of MedicineChengdu, China.
[Wang, Yi] North Sichuan Medical CollegeNanchong, China.
[Zhu, Yuchun] North Sichuan Medical CollegeNanchong, China.
[Sun, Xiaobin] The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Department of GastroenterologyChengdu, China.
[Guo, Yuanbiao] The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Medical Research CenterChengdu, China.
[Shan, Jing] The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Department of GastroenterologyChengdu, China.
RP Shan, J (reprint author), The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Department of Gastroenterology, Chengdu, China.
EM tulip-sj@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610474
EP 1610485
DI 10.3389/pore.2022.1610474
PG 12
ER
PT J
AU Zhou, Z
Huang, D
Yang, Sh
Liang, J
Wang, X
Rao, Q
AF Zhou, Zhiyi
Huang, Dandan
Yang, Shudong
Liang, Jiabei
Wang, Xuan
Rao, Qiu
TI Clinicopathological Significance, Related Molecular Changes and Tumor Immune Response Analysis of the Abnormal SWI/SNF Complex Subunit PBRM1 in Gastric Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; PD-L1; gastric adenocarcinoma (GAC); PBRM1; microsatellite stability; tumor-infiltrating lymphocytes (TIL)
ID prognosis; PD-L1; gastric adenocarcinoma (GAC); PBRM1; microsatellite stability; tumor-infiltrating lymphocytes (TIL)
AB Background: PBRM1 gene abnormalities were recently found to play a role in tumor development and tumor immune activity. This article will explore the clinicopathological and molecular changes and tumor immune activity of the abnormal SWI/SNF complex subunit PBRM1 in gastric adenocarcinoma (GAC) and its significance. Methods: The cBioPortal, LinkedOmics and TISIDB datasets were used to analyze the abnormality of the PBRM1 gene in GAC and its relationship with prognosis, related molecular changes and tumor-infiltrating lymphocytes (TILs). In addition, 198 GAC cases were collected to further study the relationship between the loss/attenuation of PBRM1 expression and clinicopathology, prognosis, microsatellite stability, PD-L1 expression and TIL in GAC. DNA whole-exome sequencing was performed on 7 cases of gastric cancer with loss of PBRM1 expression. Results: The cBioPortal data showed that PBRM1 deletion/mutation accounted for 7.32% of GAC and was significantly associated with several molecular changes, such as molecular subtypes of GAC. The LinkedOmics dataset showed that PBRM1 mutation and its promoter DNA methylation showed lower PBRM1 mRNA expression, and PBRM1 mutation cases showed significantly higher mRNA expression of PD-L1 (CD274). TISIDB data showed that PBRM1 abnormalities were significantly positively associated with multiple TILs. In our group of 198 cases, the loss/attenuation of PBRM1 expression was significantly positively correlated with intra-tumoral tumor infiltrating lymphocytes (iTILs) and deficient MMR and PD-L1 expression. Kaplan–Meier survival analysis showed that the overall survival of GAC patients with loss/attenuation of PBRM1 expression was significantly better (p = 0.023). iTIL was an independent prognostic factor of GAC. Loss of PBRM1 expression often co-occurs with mutations in other SWI/SNF complex subunit genes, and there are some repetitive KEGG signaling changes. Conclusion: Abnormality of the PBRM1 gene may be related to the occurrence of some GACs and can affect tumor immune activity, thereby affecting clinicopathology and prognosis. It may be a potentially effective predictive marker for immunotherapy and a novel therapeutic approach associated with synthetic lethality.
C1 [Zhou, Zhiyi] The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Department of PathologyWuxi, China.
[Huang, Dandan] The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Digestive Endoscopic CenterWuxi, China.
[Yang, Shudong] The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Department of PathologyWuxi, China.
[Liang, Jiabei] The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Department of PathologyWuxi, China.
[Wang, Xuan] Nanjing University School of Medicine, Jinling Hospital, Department of PathologyNanjing, China.
[Rao, Qiu] Nanjing University School of Medicine, Jinling Hospital, Department of PathologyNanjing, China.
RP Rao, Q (reprint author), Nanjing University School of Medicine, Jinling Hospital, Department of Pathology, Nanjing, China.
EM nanjing_raoq@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610479
EP 1610490
DI 10.3389/pore.2022.1610479
PG 12
ER
PT J
AU Fang, Z
Wang, F
Zhang, M
Huang, H
Lin, Z
AF Fang, Zhijie
Wang, Feifei
Zhang, Mengya
Huang, Hua
Lin, Zhiqiang
TI Identification of Co-Expression Modules and Genes Associated With Tumor Progression in Oral Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor progression; WGCNA; prognostic markers; OSCC; hub-gene
ID tumor progression; WGCNA; prognostic markers; OSCC; hub-gene
AB Oral squamous cell carcinoma (OSCC) is a common head-and-neck cancer with a deficiency of early diagnosis and poor prognosis. To identify potential diagnostic and prognostic markers of OSCC, we firstly used weighted gene co-expression network analysis (WGCNA) to build a co-expression module from GSE42743. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on specified units from selected modules utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID). Additionally, we identified and validate hub genes of these specified modules from multiple datasets like GEPIA and TCGA. In total 16 co-expression modules were built by 17,238 genes of 74 tumor samples utilizing WGCNA. Through pathway and functional enrichment analysis, the turquoise module was most firmly relevant to the cell cycle, oocyte meiosis, and p53 signaling pathway. Hub genes VRK1, NUP37, HMMR, SPC25, and RUVBL1 were identified to be related to oral cancer at both molecular level and clinical levels. The expressions of these genes differed in tumor tissues and normal tissues. Meanwhile, patients with high hub gene expression had a poor prognosis clinically. To conclude, five hub genes were identified to be relevant to oral cancer from the molecular level and the clinical level. Therefore, the detection of these genes was of great significance. They can be regarded as diagnostic and prognostic biomarkers for oral cancer. Also, they could shed light on the improvement of patients’ overall survival and prognosis, which needs further analysis in the future.
C1 [Fang, Zhijie] Gusu School, Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Department of OtolaryngologySuzhou, China.
[Wang, Feifei] The Affiliated BenQ Hospital of Nanjing Medical University, Suzhou BenQ Medical Center, Department of NursingSuzhou, China.
[Zhang, Mengya] Gusu School, Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Department of OtolaryngologySuzhou, China.
[Huang, Hua] Gusu School, Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Department of OtolaryngologySuzhou, China.
[Lin, Zhiqiang] Gusu School, Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Department of OtolaryngologySuzhou, China.
RP Lin, Z (reprint author), Gusu School, Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Department of Otolaryngology, Suzhou, China.
EM 865205697@qq.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610481
EP 1610492
DI 10.3389/pore.2022.1610481
PG 12
ER
PT J
TI The Prognostic Value of Eight Immunohistochemical Markers Expressed in the Tumor Microenvironment and on Hodgkin Reed-Sternberg Cells in Pediatric Patients With Classical Hodgkin Lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; prognostic value; children; pediatric; classical Hodgkin lymphoma; immunohistochemical markers; prognostic markers
ID prognosis; prognostic value; children; pediatric; classical Hodgkin lymphoma; immunohistochemical markers; prognostic markers
AB Immunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC at diagnosis is associated with disease free survival (DFS) and with interim remission status. Low CD15 and low TARC expression were associated with relapsed disease. Low expression of PD-L1 was associated with complete remission at interim PET-scan. Our data suggest a difference between pediatric and adult cHL. This underlines the importance of future research into specific prognostic factors in pediatric cHL, indispensable for improvement of treatment in this population.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610482
EP 1610489
DI 10.3389/pore.2022.1610482
PG 8
ER
PT J
AU Zhao, Y
Song, X
Song, X
Xie, L
AF Zhao, Yajing
Song, Xingguo
Song, Xianrang
Xie, Li
TI Identification of Diagnostic Exosomal LncRNA-miRNA-mRNA Biomarkers in Colorectal Cancer Based on the ceRNA Network
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; lncRNA; miRNA; exosomes; diagnostic biomarker; mRNA
ID colorectal cancer; lncRNA; miRNA; exosomes; diagnostic biomarker; mRNA
AB Background: Colorectal cancer (CRC) is currently the fourth most common cancer worldwide. The roles of exosomal competing endogenous RNAs (ceRNAs) in CRC remain unclear. In this study, we constructed an exosomal ceRNA network to identify the core ceRNAs and investigate the diagnostic biomarkers in CRC. Methods and Patients: Serum exosomes were isolated from four CRC patients and two healthy donors by ultracentrifugation, and then subjected to RNA isolation, sequencing and microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were performed to identify functional enrichment implications of differentially expressed exosomal mRNAs. TargetScan and miRanda were used for identifying the miRNA-mRNA and miRNA-LncRNA interactions. The predicted lncRNAs and mRNAs were intersected with the differentially expressed genes, for which the screening criterion was fold change >1.5 in the microarray. Differentially expressed exosomal miRNAs were identified in the GSE71008 dataset, and differentially expressed mRNAs (DEmRNAs) were further summarized from The Cancer Genome Atlas (TCGA) database. Results: A total of 1186 exosomal DEmRNAs, 2088 exosomal DElncRNAs and 29 exosomal miRNAs were detected in CRC patients compared to the healthy donors. Functional enrichment analysis suggested that exosomal DEmRNAs might participate in pathways related to carcinogenesis and development of cancer. An exosomal ceRNA regulatory network of CRC was constructed based on 40 lncRNAs, two miRNAs, and five mRNAs. Exosomal miR-150-5p and miR-10b-5p expression levels were increased in healthy donors compared with CRC patients in the GSE71008 dataset, and five DEmRNAs (TOMM70A, RBM48, BEND3, RHOBTB1, and ADAMTS2) were significantly upregulated in TCGA database. Two potential exosomal regulatory axes of lncRNA G016261-miR-150-5p-RBM48 and lncRNA XLOC_011677-miR-10b-5p-BEND3 were identified from the network. Conclusion: The current study revealed potential molecular biological regulation pathways and diagnostic biomarkers through the exosomal ceRNA regulatory network.
C1 [Zhao, Yajing] Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Department of Clinical LaboratoryJinan, China.
[Song, Xingguo] Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Department of Clinical LaboratoryJinan, China.
[Song, Xianrang] Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Department of Clinical LaboratoryJinan, China.
[Xie, Li] Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Department of Clinical LaboratoryJinan, China.
RP Xie, L (reprint author), Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Department of Clinical Laboratory, Jinan, China.
EM l_xie2001@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610493
EP 1610503
DI 10.3389/pore.2022.1610493
PG 11
ER
PT J
AU Wang, L
Xiao, Sh
Zheng, Y
Gao, Z
AF Wang, Longyue
Xiao, Shuaishuai
Zheng, Yiming
Gao, Zefeng
TI Interaction Between Vascular Endothelial Growth Factor Gene Polymorphism and Smoking on Gastric Cancer Risk in Chinese Han Population
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; smoking; interaction; single nucleotide polymorphisms; vascular endothelial growth factor
ID gastric cancer; smoking; interaction; single nucleotide polymorphisms; vascular endothelial growth factor
AB Aim: In this study, we aimed to evaluate the associations of vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms (SNPs) and its interaction with current smoking with gastric cancer (GC) risk in the Chinese Han population. Methods: We used logistic regression model to test the association between VEGF gene polymorphism and the risk of GC. The association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI) calculated using logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the effect of the interaction between VEGF gene and current smoking on GC risk. Results: Logistic regression analysis showed that the risk of GC was significantly higher in rs10434 -G allele carriers than that in AA genotype carriers (AG + GG and AA), and the adjusted OR (95% CI) = 1.64 (1.24–2.08). In addition, we found a significantly higher GC risk in subjects with rs833061-T allele than those with CC allele (CT + TT and CC), adjusted or (95% CI) = 1.43 (1.10–1.87). We also found a statistically significant two- locus model (p = 0.018), including rs10434 and current smoking, indicating a significant interaction between rs10434 and current smoking on the risk of GC. Hierarchical analysis found that current smokers with AG or GG genotype have the highest GC risk, compared to neversmokers with AA genotype, OR (95% CI) = 2.43 (1.64–3.28). Conclusion: We found that rs10434 -G and rs833061-T alleles, gene- environment interaction between rs10434, and current smoking were all related to increased GC risk.
C1 [Wang, Longyue] Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Department of General Surgery TwoTaiyuan, China.
[Xiao, Shuaishuai] Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Department of General Surgery TwoTaiyuan, China.
[Zheng, Yiming] Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Department of General Surgery TwoTaiyuan, China.
[Gao, Zefeng] Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Department of General Surgery TwoTaiyuan, China.
RP Wang, L (reprint author), Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Department of General Surgery Two, Taiyuan, China.
EM wanglongyue661@163.com
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2018, 68(6):394–424., DOI 10.3322/caac.21492
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610495
EP 1610500
DI 10.3389/pore.2022.1610495
PG 6
ER
PT J
AU Chien, ChYCh
Beke, L
Mehes, G
Mokanszki, A
AF Chien, Chang Yi-Che
Beke, Livia
Mehes, Gabor
Mokanszki, Attila
TI Anastomosing Haemangioma: Report of Three Cases With Molecular and Immunohistochemical Studies and Comparison With Well-Differentiated Angiosarcoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE angiosarcoma; anastomosing haemangioma; immunohistochemistry (IHC); fluorescence in situ hybridization (FISH); next-generation sequencing (NGS); GNA11 mutation
ID angiosarcoma; anastomosing haemangioma; immunohistochemistry (IHC); fluorescence in situ hybridization (FISH); next-generation sequencing (NGS); GNA11 mutation
AB Anastomosing haemangioma (AH) is a newly described distinct vascular neoplasm that histologically may confuse with well-differentiated angiosarcoma (AS) for those who are unfamiliar with this rare entity. We aimed to identify molecular genetic differences between AHs and ASs by carrying out immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Immunohistochemically, all six cases showed positivity for cyclinD1 and pERK. All cases of AH showed focal weak positive reaction for p53 and MIB-1, and the IHCs for HIF-1α were all negative for all three cases. Those three cases of angiosarcoma revealed strong, diffuse positivity for p53, 50%–70% MIB-1 labelling, and multifocal, moderate to strong HIF-1α expression. To further clarify the difference in p53 expression, we carried out a FISH which revealed 17p polysomy in all three ASs whereas copy number aberration was absent in the AH group. In one AH case, the GNA11 c.627G > T nucleotide variant was detected. Due to the rarity and overlapping morphological features, AH might be difficult to separate from other vascular tumours, in particular from well-differentiated AS also featured by mild hyperchromatic, hobnail-like endothelial cells. The potential molecular differences between these two entities presented here may be used in support of the correct diagnosis.
C1 [Chien, Chang Yi-Che] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Beke, Livia] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Mokanszki, Attila] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
RP Chien, ChYCh (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, Debrecen, Hungary.
EM dr.changchien.yiche@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610498
EP 1610503
DI 10.3389/pore.2022.1610498
PG 6
ER
PT J
TI The Role of Tumor Microenvironment and Immune Response in Colorectal Cancer Development and Prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE colorectal cancer; tumor microenvironment; immune cells; tumorigenesis; consensus molecular subtypes; immunoscore
ID colorectal cancer; tumor microenvironment; immune cells; tumorigenesis; consensus molecular subtypes; immunoscore
AB Colorectal cancer (CRC) is one of the most common cancers worldwide. The patient’s prognosis largely depends on the tumor stage at diagnosis. The pathological TNM Classification of Malignant Tumors (pTNM) staging of surgically resected cancers represents the main prognostic factor and guidance for decision-making in CRC patients. However, this approach alone is insufficient as a prognostic predictor because clinical outcomes in patients at the same histological tumor stage can still differ. Recently, significant progress in the treatment of CRC has been made due to improvements in both chemotherapy and surgical management. Immunotherapybased approaches are one of the most rapidly developing areas of tumor therapy. This review summarizes the current knowledge about the tumor microenvironment (TME), immune response and its interactions with CRC development, immunotherapy and prognosis.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610502
EP 1610513
DI 10.3389/pore.2022.1610502
PG 12
ER
PT J
AU Zhou, M
Chen, Y
Gu, X
Wang, C
AF Zhou, Min
Chen, Yan
Gu, Xuyu
Wang, Cailian
TI A Comprehensive Bioinformatic Analysis for Identification of Myeloid-Associated Differentiation Marker as a Potential Negative Prognostic Biomarker in Non-Small-Cell Lung Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bioinformatics; biomarker; NSCLC; survival-related gene; MYADM
ID bioinformatics; biomarker; NSCLC; survival-related gene; MYADM
AB Objectives: This study aimed to identify a molecular marker associated with the prognosis of non-small-cell lung cancer (NSCLC). Materials and Methods: The RNA sequencing data and clinical information of NSCLC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression gene modules and differentially expressed genes (DEGs) by comparing gene expression between NSCLC tumor tissues and normal tissues. Subsequently, the functional enrichment analysis of the DEGs was performed. Kaplan- Meier survival analysis and the GEPIA2 online tool were performed to investigate the relationship between the expression of these genes of interest and the survival of NSCLC patients, and to validate one most survival-relevent hub gene, as well as validated the hub gene using independent datasets from the GEO database. Further analysis was carried out to characterize the relationship between the hub gene and tumor immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and other known biomarkers of lung cancer. The related genes were screened by analyzing the protein-protein interaction (PPI) network and the survival model was constructed. GEPIA2 was applied in the potential analysis of pan-cancer biomarker of hub gene. Results: 57 hub genes were found to be involved in intercellular connectivity from the 779 identified differentially co-expressed genes. Myeloid-associated differentiation marker (MYADM) was strongly associated with overall survival (OS) and disease-free survival (DFS) of NSCLC patients, and high MYADM expression was associated with poor prognosis. Thus, MYADM was identified as a risk factor. Additionally, MYADM was validated as a survival risk factor in NSCLC patients in two independent datasets. Further analysis showed that MYADM was nagetively associated with TMB, and was positively correlated with macrophages, neutrophils, and dendritic cells, suggesting its role in regulating tumor immunity. The MYADM expression differed across many types of cancer and had the potential to serve as a pan-cancer marker. Conclusion: MYADM is an independent prognostic factor for NSCLC patients, which can predict the progression of cancer and play a role in the tumor immune cell infiltration in NSCLC.
C1 [Zhou, Min] Southeast University, School of Medicine, Zhongda Hospital, Department of OncologyNanjing, China.
[Chen, Yan] Southeast University, School of Medicine, Zhongda Hospital, Department of OncologyNanjing, China.
[Gu, Xuyu] Southeast University, School of Medicine, Zhongda Hospital, Department of OncologyNanjing, China.
[Wang, Cailian] Southeast University, School of Medicine, Zhongda Hospital, Department of OncologyNanjing, China.
RP Wang, C (reprint author), Southeast University, School of Medicine, Zhongda Hospital, Department of Oncology, Nanjing, China.
EM wangcailian65@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610504
EP 1610515
DI 10.3389/pore.2022.1610504
PG 12
ER
PT J
AU Jiang, L
Li, D
Wang, Ch
Liao, J
Liu, J
Wei, Q
Wang, Y
AF Jiang, Lucen
Li, Dan
Wang, Chao
Liao, Jia
Liu, Jianghuan
Wei, Qingzhu
Wang, Yiyang
TI Decreased Expression of Karyopherin-α 1 is Related to the Malignant Degree of Cervical Cancer and is Critical for the Proliferation of Hela Cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cervical cancer; proliferation; KPNA1; Hela cell; malignant
ID cervical cancer; proliferation; KPNA1; Hela cell; malignant
AB Karyopherin α (KPNA) proteins are involved in nucleocytoplasmic trafficking and are critical for protein subcellular localization. Recent studies have suggested that KPNA proteins are abnormally expressed in various solid tumors. The objective of this study was to investigate the expression of KPNA1 and KPNA2 in cervical cancer tissue with different histologic grades and cell lines, as well as the effects of the KPNA1 expression level on Hela cell proliferation. We collected the medical data of 106 patients with cervical cancer and investigated the protein expression of KPNA1 and KPNA2 by immunohistochemistry and western blot. The results revealed a significantly lower expression of KPNA1 in cervical cancer compared to normal tissue. Conversely, stronger staining intensity for KPNA2 was observed in cervical tumor samples. The expression levels of KPNA1 and KPNA2 were significantly associated with the tumor histologic grade. The weakest KPNA1 expression and strongest staining for KPNA2 were observed in grade III tumor tissue. The expression levels of KPNA1 were lower in Hela and C33A cells compared with normal human cervical epithelial cells; however, the expression of KPNA2 exhibited an opposite trend. The upregulation of KPNA1 significantly suppressed the proliferation of Hela cells and relevant proteins expression, as well as promoted transportation of IRF3 into nucleus. Our results suggest the downregulation of KPNA1 expression is related to the malignant degree of cervical cancer and is closely associated with the proliferation of cervical cancer cells.
C1 [Jiang, Lucen] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
[Li, Dan] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
[Wang, Chao] The Sixth Affiliated Hospital of Sun Yat-Sen University, Department of PathologyGuangzhou, China.
[Liao, Jia] Jinan University, School of Medicine, Department of PathophysiologyGuangzhou, China.
[Liu, Jianghuan] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
[Wei, Qingzhu] Southern Medical University, College of Basic Medicine, Department of PathologyGuangzhou, China.
[Wang, Yiyang] Jinan University, School of Medicine, Department of PathophysiologyGuangzhou, China.
RP Wang, Y (reprint author), Jinan University, School of Medicine, Department of Pathophysiology, Guangzhou, China.
EM wangyiyang@jnu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610518
EP 1610527
DI 10.3389/pore.2022.1610518
PG 10
ER
PT J
AU Kiraly, Zs
Szepesi,
Sebestyen, A
Kuroli, E
Rencz, F
Toth, B
Bokor, L
Szakonyi, J
Medvecz, M
Hidvegi, B
AF Kiraly, Zsofia
Szepesi, Agota
Sebestyen, Anna
Kuroli, Eniko
Rencz, Fanni
Toth, Bela
Bokor, Laura
Szakonyi, Jozsef
Medvecz, Marta
Hidvegi, Bernadett
TI Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PD-L1; PD-1; subacute cutaneous lupus erythematosus; discoid lupus erythematosus; PD-1 inhibitorinduced SCLE; TEN-like lupus
ID PD-L1; PD-1; subacute cutaneous lupus erythematosus; discoid lupus erythematosus; PD-1 inhibitorinduced SCLE; TEN-like lupus
AB The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DISCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%–70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.
C1 [Kiraly, Zsofia] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Szepesi, Agota] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kuroli, Eniko] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Rencz, Fanni] Corvinus University of Budapest, Department of Health EconomicsBudapest, Hungary.
[Toth, Bela] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Bokor, Laura] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Szakonyi, Jozsef] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Medvecz, Marta] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Hidvegi, Bernadett] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
RP Kiraly, Zs (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Budapest, Hungary.
EM kiraly.zsofia@phd.semmelweis.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610521
EP 1610527
DI 10.3389/pore.2022.1610521
PG 7
ER
PT J
AU Zhang, Y
Li, L
Chu, F
Xiao, X
Zhang, L
Li, K
Wu, H
AF Zhang, Yong
Li, Lu
Chu, Feifei
Xiao, Xingguo
Zhang, Li
Li, Kunkun
Wu, Huili
TI Identification and Validation of an m6A-Related LncRNA Signature to Predict Progression-Free Survival in Colorectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; lncRNA; signature; m6A; progression free survival
ID colorectal cancer; lncRNA; signature; m6A; progression free survival
AB The RNA methylation of N6 adenosine (m6A) plays a crucial role in various biological processes. Strong evidence reveals that the dysregulation of long non-coding RNAs (lncRNA) brings about the abnormality of downstream signaling in multiple ways, thus influencing tumor initiation and progression. Currently, it is essential to discover effective and succinct molecular biomarkers for predicting colorectal cancer (CRC) prognosis. However, the prognostic value of m6A-related lncRNAs for CRC remains unclear, especially for progression-free survival (PFS). Here, we screened 24 m6A-related lncRNAs in 622 CRC patients and identified five lncRNAs (SLCO4A1-AS1, MELTFAS1, SH3PXD2A-AS1, H19 and PCAT6) associated with patient PFS. Compared to normal samples, their expression was up-regulated in CRC tumors from TCGA dataset, which was validated in 55 CRC patients fromour in-house cohort. We established an m6ALnc signature for predicting patient PFS, which was an independent prognostic factor by classification analysis of clinicopathologic features. Moreover, the signature was validated in 1,077 patients from six independent datasets (GSE17538, GSE39582, GSE33113, GSE31595, GSE29621, and GSE17536), and it showed better performance than three known lncRNA signatures for predicting PFS. In summary, our study demonstrates that the m6A-Lnc signature is a promising biomarker for forecasting patient PFS in CRC.
C1 [Zhang, Yong] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Li, Lu] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Chu, Feifei] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Xiao, Xingguo] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Zhang, Li] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Li, Kunkun] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
[Wu, Huili] Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of GastroenterologyZhengzhou, China.
RP Wu, H (reprint author), Zhengzhou Central Hospital Affiliated to Zhengzhou University, Department of Gastroenterology, Zhengzhou, China.
EM wuhuili660912@zzu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610536
EP 1610548
DI 10.3389/pore.2022.1610536
PG 13
ER
PT J
AU Kispal, M
Janvary, ZsL
Balatoni, T
Gabor, S
Fedorcsak, I
Katalin, B
Kenessey, I
Liszkay, G
AF Kispal, Mihaly
Janvary, Zsolt Levente
Balatoni, Timea
Gabor, Stelczer
Fedorcsak, Imre
Katalin, Bocs
Kenessey, Istvan
Liszkay, Gabriella
TI The Role of Stereotactic Radiotherapy in the Management of Melanoma, A Retrospective Single Institute Preliminary Study of 30 Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE skin cancer; stereotactic radiation therapy; targeted therapy; immunotherapy; melanoma
ID skin cancer; stereotactic radiation therapy; targeted therapy; immunotherapy; melanoma
AB Cutaneous melanoma is the third most common type of skin cancer in the world. The incidence of melanoma is increasing in most countries, however, mortality seems to be slowly decreasing. The treatment of advanced cutaneous melanoma changed radically since 2011. The new therapeutic modalities, such as immuno- and targeted therapies give a chance to successfully reach more prolonged progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma. Despite the great therapeutic benefit, most patients eventually develop resistance to these therapies, and the disease will progress. In some cases oligoprogression develops. In those cases local therapy, such as stereotactic radiotherapy can make it possible to continue the previously applied effective medical treatment for the benefit of patients. In our study of a total of 30 patients—20 of them received pre-treatment with systemic medical therapy—received stereotactic radiotherapy using various systems, in the National Institute of Oncology, Hungary, Budapest. We managed to prolong the systemic therapy for 12.5 months median period with the assistance of CyberKnife technique. Therapy related adverse events were mostly tolerable with only 3% of Grade 3 toxicity. We concluded that stereotactic radiotherapy and stereotactic radiosurgery, are safe, and effective therapeutic modalities for regional tumor control in cases of oligoprogression
C1 [Kispal, Mihaly] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Janvary, Zsolt Levente] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Balatoni, Timea] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
[Gabor, Stelczer] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Fedorcsak, Imre] Orszagos Pszichiatriai es Neurologiai IntezetBudapest, Hungary.
[Katalin, Bocs] National Institute of Oncology, Center of RadiologyBudapest, Hungary.
[Kenessey, Istvan] National Institute of Oncology, National Cancer RegistryBudapest, Hungary.
[Liszkay, Gabriella] National Institute of Oncology, Department of DermatologyBudapest, Hungary.
RP Kispal, M (reprint author), National Institute of Oncology, Department of Dermatology, Budapest, Hungary.
EM kispal.mihaly90@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610550
EP 1610559
DI 10.3389/pore.2022.1610550
PG 10
ER
PT J
AU Zhou, L
Wu, H
Bai, X
Min, Sh
Zhang, J
Li, C
AF Zhou, Lixia
Wu, Huiqin
Bai, Xingli
Min, Shuyun
Zhang, Jiawen
Li, Cunli
TI O-Glycosylating Enzyme GALNT2 Predicts Worse Prognosis in Cervical Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; cervical cancer; GALNT2; anti-tumor immune response; immune-related biomarker
ID survival; cervical cancer; GALNT2; anti-tumor immune response; immune-related biomarker
AB Identification of novel biomarkers is helpful for the diagnosis and treatment of cervical cancer. Mucin glycosylating enzyme GALNT2 modulates mucin O-glycosylation, and has been revealed as a regulator of tumorigenesis in various cancers. However, the expression pattern of GALNT2 in cervical cancer is still unclear. In this study, we demonstrated that the mRNA expression and protein level of GALNT2 were increased in cervical high-grade intraepithelial neoplasia and tumor tissues compared with normal cervix tissues. Kaplan-Meier plotter showed that overexpression of GALNT2 was associated with worse overall survival in TCGA cohort (p < 0.001, HR = 2.65, 95% CI = 1.62–4.34) and poor disease free survival in GSE44001 cohort (p = 0.0218, HR = 2.15, 95% CI = 1.14–4.06). In addition, GSEA analysis showed that various immune-related pathways were closely related to the expression of GALNT2 in cervical cancer. Moreover, coexpression of GALNT2 and IL1A, IL1B, IL11, CXCL1, CXCL2, CXCL5, CXCL6, CXCR1, or CCR3 predicted poor overall survival, and the expression of GALNT2 also affected the prognostic value of CD47, CD274, CD276, CSF1R, TNFSF9, and TNFSF11 in cervical cancer patients. These findings suggest that GALNT2 might be used as a prognostic biomarker in cervical cancer.
C1 [Zhou, Lixia] Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and GynecologyShanghai, China.
[Wu, Huiqin] Shanghai Songjiang DistrictMaternal and Child Health Hospital, Department of Obstetrics and GynecologyShanghai, China.
[Bai, Xingli] Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and GynecologyShanghai, China.
[Min, Shuyun] Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and GynecologyShanghai, China.
[Zhang, Jiawen] Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and GynecologyShanghai, China.
[Li, Cunli] Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and GynecologyShanghai, China.
RP Li, C (reprint author), Shanghai Jiao Tong University School of Medicine, Jiading Branch of Shanghai General Hospital, Department of Obstetrics and Gynecology, Shanghai, China.
EM lcllzr2019@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610554
EP 1610564
DI 10.3389/pore.2022.1610554
PG 11
ER
PT J
AU Wu, J
He, B
Miao, M
Han, X
Dai, H
Dou, H
Li, Y
Zhang, X
Wang, G
AF Wu, Jie
He, Baojun
Miao, Miao
Han, Xibin
Dai, Hongyan
Dou, Heng
Li, Yanqiu
Zhang, Xiaoqing
Wang, Guangchuan
TI Enhancing Natural Killer Cell-Mediated Cancer Immunotherapy by the Biological Macromolecule Nocardia rubra Cell-Wall Skeleton
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; metastasis; natural killer cell; Nocardia rubra cell-wall skeleton; cytotoxicity
ID cancer; metastasis; natural killer cell; Nocardia rubra cell-wall skeleton; cytotoxicity
AB The biological macromolecule Nocardia rubra cell-wall skeleton (Nr-CWS) has wellestablished immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. In vitro, the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27lowCD11bhigh), and up-regulating the production of cytokines and cytotoxic molecules.
C1 [Wu, Jie] The First Affiliated Hospital of Jinzhou Medical University, Department of OncologyJinzhou, China.
[He, Baojun] The First Affiliated Hospital of Jinzhou Medical University, Department of Clinical Laboratory MedicineJinzhou, China.
[Miao, Miao] Jinzhou Medical University, School of Basic Medical Science, Department of ImmunologyJinzhou, China.
[Han, Xibin] Jinzhou Medical University, Laboratory Animal CenterJinzhou, China.
[Dai, Hongyan] The First Affiliated Hospital of Jinzhou Medical University, Department of Outpatient PICCJinzhou, China.
[Dou, Heng] Greatest Biopharma Limited CompanyBenxi, China.
[Li, Yanqiu] Greatest Biopharma Limited CompanyBenxi, China.
[Zhang, Xiaoqing] China Medical University, Teaching Center for Basic Medical ExperimentShenyang, China.
[Wang, Guangchuan] Jinzhou Medical University, School of Basic Medical Science, Department of ImmunologyJinzhou, China.
RP Wang, G (reprint author), Jinzhou Medical University, School of Basic Medical Science, Department of Immunology, Jinzhou, China.
EM chuan560@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610555
EP 1610563
DI 10.3389/pore.2022.1610555
PG 9
ER
PT J
AU Chen, X
Hu, G
Xiong, L
Xu, Q
AF Chen, Xi
Hu, Gang
Xiong, Li
Xu, Qingqing
TI Relationships of Cuproptosis-Related Genes With Clinical Outcomes and the Tumour Immune Microenvironment in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; hepatocellular carcinoma; immune infiltration; prognostic model; cuproptosis
ID immunotherapy; hepatocellular carcinoma; immune infiltration; prognostic model; cuproptosis
AB Background: Cuproptosis is a recently identified form of regulated cell death that plays a critical role in the onset and progression of various cancers. However, the effects of cuproptosis-related genes (CRGs) on hepatocellular carcinoma (HCC) are poorly understood. This study aimed to identify the cuproptosis subtypes and established a novel prognostic signature of HCC. Methods: We collected gene expression data and clinical outcomes from the TCGA, ICGC, and GEO datasets, analysed and identified 16 CRGs and the different subtypes of cuproptosis related to overall survival (OS), and further examined the differences in prognosis and immune infiltration among the subtypes. Subtypes-related differentially expressed genes (DEGs) were employed to build a prognostic signature. The relationship of the signature with the immune landscape as well as the sensitivity to different therapies was explored. Moreover, a nomogram was constructed to predict the outcome based on different clinicopathological characteristics. Results: Three cuproptosis subtypes were identified on the basis of 16 CRGs, and subtype B had an advanced clinical stage and worse OS. The immune response and function in subtype B were significantly suppressed, which may be an important reason for its poor prognosis. Based on the DEGs among the three subtypes, a prognostic model of five CRGs was constructed in the training set, and its predictive ability was validated in two external validation sets. HCC patients were classified into high and low-risk subgroups according to the risk score, and found that patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (p < 0.001). The independent predictive performance of the risk score was assessed and verified by multivariate Cox regression analysis (p < 0.001). We further created an accurate nomogram to improve the clinical applicability of the risk score, showing good predictive ability and calibration. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the highrisk group were found to be resistant to immunotherapy and a variety of chemotherapy drugs. Conclusion: Our study identified three cuproptosis subtypes and established a novel prognostic model that provides new insights into HCC subtype prognostic assessment and guides more effective treatment regimens.
C1 [Chen, Xi] Edong Healthcare Group, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic UniversityHuangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Department of Thoracic OncologyHuangshi, China.
[Hu, Gang] Edong Healthcare Group, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Department of Breast Surgery, Thyroid SurgeryHuangshi, China.
[Xiong, Li] Edong Healthcare Group, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Department of RadiologyHuangshi, China.
[Xu, Qingqing] Edong Healthcare Group, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Department of PathologyHuangshi, China.
RP Xu, Q (reprint author), Edong Healthcare Group, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Department of Pathology, Huangshi, China.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610558
EP 1610569
DI 10.3389/pore.2022.1610558
PG 12
ER
PT J
AU Lin, Y
Li, Y
Chen, X
Chen, M
Huang, J
Guo, W
Chen, L
Wu, L
Zhang, X
Zhang, W
Jin, X
Zhang, J
Fu, F
Wang, Ch
AF Lin, Yuxiang
Li, Yan
Chen, Xiaobin
Chen, Minyan
Huang, Jun
Guo, Wenhui
Chen, Lili
Wu, Long
Zhang, Xiang
Zhang, Wenzhe
Jin, Xuan
Zhang, Jie
Fu, Fangmeng
Wang, Chuan
TI Thrombospondin 2 is a Functional Predictive and Prognostic Biomarker for Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; pathological response; neoadjuvant chemotherapy; triple-negative breast cancer; THBS2
ID biomarker; pathological response; neoadjuvant chemotherapy; triple-negative breast cancer; THBS2
AB Background: Triple-negative breast cancer (TNBC) is characterized by a more aggressive biological behavior and unfavorable outcome. Circulating and histological expression of THBS2 has been demonstrated to be a novel diagnostic and prognostic biomarker in patients with various types of tumors. However, few studies have evaluated the predictive and prognostic value of THBS2 in TNBC specifically. Methods: In total, 185 triple-negative breast cancer patients (TNBC) with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC and at surgery by enzyme-linked immunosorbent assay (ELISA). Histological THBS2 (hTHBS2) expression in patients with residual tumors was evaluated by immunohistochemistry (IHC) staining method. Correlations between variables and treatment response were studied. Kaplan-Meier plots and Cox proportional hazard regression model were applied for survival analysis. Functional activities of THBS2 in TNBC cells were determined by CCK-8 assay, colony formation, wound healing, and transwell assay. Results: Of the 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with a lower level of sTHBS2 at surgery and higher level of sTHBS2 change (OR = 0.88, 95%CI: 0.79–0.98, p = 0.020 and OR = 1.12, 95%CI: 1.02–1.23, p = 0.015, respectively). In survival analysis, hTHBS2 expression in residual tumor was of independent prognostic value for both disease-free survival (HR = 2.21, 95%CI = 1.24–3.94, p = 0.007) and overall survival (HR = 2.07, 95%CI = 1.09–3.92, p = 0.026). For functional studies, THBS2 was indicated to inhibit proliferation, migration, and invasion abilities of TNBC cells in vitro. Conclusion: Our findings confirmed the value of serum THBS2 level to predict pCR for TNBC patients and the prognostic performance of histological THBS2 expression in nonpCR responders after NAC. THBS2 might serve as a promising functional biomarker for patients with triple-negative breast cancer.
C1 [Lin, Yuxiang] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Li, Yan] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Chen, Xiaobin] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Chen, Minyan] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Huang, Jun] Fujian Medical University Union Hospital, Department of Laboratory MedicineFuzhou, China.
[Guo, Wenhui] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Chen, Lili] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Wu, Long] Fujian Medical University Union Hospital, Department of PathologyFuzhou, China.
[Zhang, Xiang] Fujian Medical University Union Hospital Pingtan Branch, Department of PathologyFuzhou, China.
[Zhang, Wenzhe] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Jin, Xuan] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Zhang, Jie] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Fu, Fangmeng] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
[Wang, Chuan] Fujian Medical University Union Hospital, Department of Breast SurgeryFuzhou, China.
RP Wang, Ch (reprint author), Fujian Medical University Union Hospital, Department of Breast Surgery, Fuzhou, China.
EM chuanwang1968@outlook.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610559
EP 1610570
DI 10.3389/pore.2022.1610559
PG 12
ER
PT J
AU Stukaite-Ruibiene, E
Norvilas, R
Dirse, V
Stankeviciene, S
Vaitkeviciene, EG
AF Stukaite-Ruibiene, Egle
Norvilas, Rimvydas
Dirse, Vaidas
Stankeviciene, Sigita
Vaitkeviciene, Elizabeta Goda
TI Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; targeted therapy; tyrosine kinase inhibitors; acute lymphoblastic leukemia; imatinib; BCRABL1- like
ID case report; targeted therapy; tyrosine kinase inhibitors; acute lymphoblastic leukemia; imatinib; BCRABL1- like
AB Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic NUP214::ABL1 fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected NUP214::ABL1 gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant ABL1 mutations; therefore, treatment with Imatinib was added to target the NUP214::ABL1 fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase.
C1 [Stukaite-Ruibiene, Egle] Faculty of Medicine of Vilnius UniversityVilnius, Lithuania.
[Norvilas, Rimvydas] Vilnius University Hospital Santaros Klinikos, Hematology, Oncology and Transfusion Medicine CenterVilnius, Lithuania.
[Dirse, Vaidas] Vilnius University Hospital Santaros Klinikos, Hematology, Oncology and Transfusion Medicine CenterVilnius, Lithuania.
[Stankeviciene, Sigita] Vilnius University Hospital Santaros Klinikos, Center for Pediatric Oncology and HematologyVilnius, Lithuania.
[Vaitkeviciene, Elizabeta Goda] Faculty of Medicine of Vilnius UniversityVilnius, Lithuania.
RP Stukaite-Ruibiene, E (reprint author), Faculty of Medicine of Vilnius University, Vilnius, Lithuania.
EM egle.eglaite@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610570
EP 1610575
DI 10.3389/pore.2022.1610570
PG 6
ER
PT J
AU Hu, B
Hao, Sh
Miao, Y
Deng, Y
Wang, J
Wan, H
Zhang, Sh
Ji, N
Feng, J
AF Hu, Boyi
Hao, Shuyu
Miao, Yazhou
Deng, Yuxuan
Wang, Jing
Wan, Hong
Zhang, Shaodong
Ji, Nan
Feng, Jie
TI Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immune checkpoint; malignant meningiomas; PP2A inhibitor; B7-H3; tumor proliferation
ID immune checkpoint; malignant meningiomas; PP2A inhibitor; B7-H3; tumor proliferation
AB Malignantmeningiomas have a highmortality rate and short survival time and currently have no effective treatment. In our study, proteomics analysis was performed to identify highly expressed proteins as therapeutic targets in malignant meningiomas. Cell Counting Kit-8 (CCK-8) assays were performed to verify the effect of LB-100 on the growth of malignant meningiomas. In addition, immunoblotting was used to verify the expression of B7-H3 and phosphorylation of STAT1 (Tyr701) in tissues and cells. Our results show that STAT1 and CD276 (B7-H3) regulated by PP2A were enriched in GO_IMMUNE_EFFECTOR_PROCESS and GO_REGULATION_OF_IMMUNE_SYSTEM_PROCESS. The immunotherapy target protein B7-H3 was confirmed to be upregulated in malignant meningiomas compared with meningothelial (p = 0.0001) and fibroblastic (p = 0.0046) meningiomas. In vitro, the PP2A inhibitor LB-100 suppressed the growth and invasion of malignant meningioma cells. Notably, the PP2A inhibitor LB-100 increased the phosphorylation of STAT1, thereby increasing the expression of the immune checkpoint protein B7-H3 in malignant meningioma cells in vitro. In conclusion, B7-H3 was found to be upregulated in malignant meningiomas. The PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy.
C1 [Hu, Boyi] Beijing Neurosurgical InstituteBeijing, China.
[Hao, Shuyu] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Miao, Yazhou] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Deng, Yuxuan] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Wang, Jing] Beijing Neurosurgical InstituteBeijing, China.
[Wan, Hong] Beijing Neurosurgical InstituteBeijing, China.
[Zhang, Shaodong] Beijing Neurosurgical InstituteBeijing, China.
[Ji, Nan] Capital Medical University, Beijing Tiantan Hospital, Department of Neurosurgery / China National Clinical Research Center for Neurological DiseasesBeijing, China.
[Feng, Jie] Beijing Neurosurgical InstituteBeijing, China.
RP Feng, J (reprint author), Beijing Neurosurgical Institute, Beijing, China.
EM fengjie111@ccmu.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610572
EP 1610579
DI 10.3389/pore.2022.1610572
PG 8
ER
PT J
AU Kulka, J
Cserni, G
AF Kulka, Janina
Cserni, Gabor
TI Editorial: Guidelines From the Central-Eastern European Professional Consensus Statement on Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Editorial
DE breast cancer; imaging; pathology; surgery; radiotherapy; systemic treatment; follow-up and rehabilitation; psycho-oncology
ID breast cancer; imaging; pathology; surgery; radiotherapy; systemic treatment; follow-up and rehabilitation; psycho-oncology
AB Guidelines from the Central-Eastern European Professional Consensus Statement on Breast Cancer
C1 [Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Cserni, Gabor] Bacs-Kiskun County Hospital, Department of PathologyKecskemet, Hungary.
RP Cserni, G (reprint author), Bacs-Kiskun County Hospital, Department of Pathology, Kecskemet, Hungary.
EM cserni@freemail.hu
CR Kesson EM, Allardice GM, George WD, Burns HJG, Morrison DS. Effects of Multidisciplinary Team Working on Breast Cancer Survival: Retrospective, Comparative, Interventional Cohort Study of 13 722 Women. BMJ, 2012, 344: e2718., DOI 10.1136/bmj.e2718
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610587
EP 1610589
DI 10.3389/pore.2022.1610587
PG 3
ER
PT J
AU Hino, Ch
Pham, B
Gray, A
Wang, J
Castillo, RD
Akhtari, M
Liu, Y
AF Hino, Christopher
Pham, Bryan
Gray, L. Austin
Wang, Jun
Castillo, Ran Dan
Akhtari, Mojtaba
Liu, Yan
TI Clinicopathologic Features and Treatment of CD10-Positive Mantle Cell Lymphoma: A Case Report and Review of Literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; mantle cell lymphoma; CD10; CCND1; B-cell chronic lymphoproliferative disorders; immunophenotyping
ID case report; mantle cell lymphoma; CD10; CCND1; B-cell chronic lymphoproliferative disorders; immunophenotyping
AB Mantle cell lymphoma (MCL) is a rare and aggressive non-Hodgkin’s B cell lymphoma characterized by the translocation t(11;14) (q13;32) and overexpression of CCND1. MCL is immunophenotypically identified as CD20+, CD5+, CyclinD1+, CD43+, CD10−, BCL6−, and CD23−. It is often distinguished from B cell lymphomas of germinal center cell origin by the absence of CD10 expression. Here we report the unique clinicopathologic features of a patient with CD10+ MCL with gastrointestinal involvement and review current literature identifying this unique immunophenotype.
C1 [Hino, Christopher] Loma Linda University, Medical Center, Department of Internal MedicineLoma Linda, CA, USA.
[Pham, Bryan] Loma Linda University, Medical Center, Department of Internal MedicineLoma Linda, CA, USA.
[Gray, L. Austin] Loma Linda University, Department of PathologyLoma Linda, CA, USA.
[Wang, Jun] Loma Linda University, Department of PathologyLoma Linda, CA, USA.
[Castillo, Ran Dan] Loma Linda University, Department of Oncology/HematologyLoma Linda, CA, USA.
[Akhtari, Mojtaba] Loma Linda University, Department of Oncology/HematologyLoma Linda, CA, USA.
[Liu, Yan] Loma Linda University, Department of PathologyLoma Linda, CA, USA.
RP Liu, Y (reprint author), Loma Linda University, Department of Pathology, Loma Linda, USA.
EM yanliu@llu.edu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610588
EP 1610592
DI 10.3389/pore.2022.1610588
PG 5
ER
PT J
TI Stat3 Tyrosine 705 and Serine 727 Phosphorylation Associate With Clinicopathological Characteristics and Distinct Tumor Cell Phenotypes in Triple-Negative Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE clinicopathological characteristics; triple-negative breast cancer; Stat3 tyrosine phosphorylation; Stat3 serine phosphorylation; tumor cell phenotypes
ID clinicopathological characteristics; triple-negative breast cancer; Stat3 tyrosine phosphorylation; Stat3 serine phosphorylation; tumor cell phenotypes
AB Signal transducer and activator of transcription 3 (Stat3) is responsible for many aspects of normal development and contributes to the development and progression of cancer through regulating epithelial cell identity and cancer stem cells. In breast cancer, Stat3 is associated with triple-negative breast cancers (TNBC) and its function has been related to the activation of p63, itself a marker of basal-like TNBC and a master regulator of stem cell activities. Stat3 activation is controlled by dual phosphorylation at tyrosine 705 (pTyr705) and serine 727 (pSer727), although it is unclear whether these have equivalent effects, and whether they are related or independent events. To address these issues, we investigated Stat3 phosphorylation at the two sites by immunohistochemistry in 173 patients with TNBC. Stat3 phosphorylation was assessed by automated quantitative measurements of digitized scanned images and classified into four categories based on histoscore. The results were analyzed for associations with multiple markers of tumor phenotype, proliferation, BRCA status, and clinicopathological characteristics. We show that the levels of pTyr705- and pSer727-Stat3 were independent in 34% of tumors. High pTyr705-Stat3 levels were associated with the luminal differentiation markers ERβ/AR and MUC1, whereas tumors with high levels of pSer727-Stat3 were more likely to be positive for the basal marker CK5/6, but were independent of p63 and were EGFR negative. Combined high pSer727- and low Tyr705-Stat3 phosphorylation associated with basal-like cancer. Although high Stat3 phosphorylation levels were associated with less aggressive tumor characteristics, they did not associate with improved survival, indicating that Stat3 phosphorylation is an unfavorable indicator for tumors with an otherwise good prognosis according to clinicopathological characteristics. These findings also show that pTyr705-Stat3 and pSer727-Stat3 associate with specific breast tumor phenotypes, implying that they exert distinct functional activities in breast cancer.
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610592
EP 1610601
DI 10.3389/pore.2022.1610592
PG 10
ER
PT J
AU Jambor, K
Koroknai, V
Kiss, T
Szasz, I
Piko, P
Balazs, M
AF Jambor, Krisztina
Koroknai, Viktoria
Kiss, Timea
Szasz, Istvan
Piko, Peter
Balazs, Margit
TI Gene Expression Patterns of Osteopontin Isoforms and Integrins in Malignant Melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gene expression; melanoma progression; osteopontin; osteopontin splice variants; integrins
ID gene expression; melanoma progression; osteopontin; osteopontin splice variants; integrins
AB Osteopontin (OPN) is a multifunctional glycoprotein that physiologically interacts with different types of integrins. It is considered to be a possible prognostic biomarker in certain tumor types; however, various splicing isoforms exist, which have not been investigated in melanoma. We aimed to define the relative expression pattern of five OPN isoforms and clarify the prognostic significance of the splice variants in melanoma. We also aimed to investigate the expression pattern of eight integrins in the same tumors. Gene expression analyses revealed that the relative expression of OPNa, OPNb, and OPNc is significantly higher in metastatic tumors compared to primary lesions (p < 0.01), whereas the expression of OPN4 and OPN5 was low in both. The more aggressive nodular melanomas had higher expression levels compared to the superficial spreading subtype (p ≤ 0.05). The relative expression of the eight tested integrins was low, with only the expression of ITGB3 being detectable in nodular melanoma (Medianlog2 = 1.274). A positive correlation was found between Breslow thickness and the expression of OPNc variant, whereby thicker tumors (>4 mm) had significantly higher expression (p ≤ 0.05). The Breslow thickness was negatively correlated with the expression of OPN4, and similarly with ITGA2. OPNc also exhibited significant positive correlation with the presence of metastasis. Our data show that high expression of OPNa, OPNb, and especially OPNc and low expression of OPN4 and ITGA2 are associated with an advanced stage of tumor progression and poor prognosis in melanoma.
C1 [Jambor, Krisztina] Debreceni Egyetem, Egeszsegtudomanyok Doktori IskolaDebrecen, Hungary.
[Koroknai, Viktoria] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Kiss, Timea] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Szasz, Istvan] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Piko, Peter] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
[Balazs, Margit] Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai TanszekDebrecen, Hungary.
RP Balazs, M (reprint author), Debreceni Egyetem, Nepegeszsegugyi Kar, Biostatisztikai es Epidemiologiai Tanszek, Debrecen, Hungary.
EM balazs.margit@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610608
EP 1610619
DI 10.3389/pore.2022.1610608
PG 12
ER
PT J
AU Antal, I
Papai, Zs
Szendroi, M
Perlaky, T
Dezso, K
Lippai, Z
Sapi, Z
AF Antal, Imre
Papai, Zsuzsanna
Szendroi, Miklos
Perlaky, Tamas
Dezso, Katalin
Lippai, Zoltan
Sapi, Zoltan
TI The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE giant cell tumor of bone; denosumab; PDGFRβ; combination therapy; sunitinib
ID giant cell tumor of bone; denosumab; PDGFRβ; combination therapy; sunitinib
AB Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with denosumab. Based on activated receptor tyrosine kinase signaling pattern of the stromal/tumor cells, a combination treatment with denosumab and sunitinib has recently been proposed to inhibit recurrences. This prompted us to investigate the PDGFRβ expression of five denosumab treated cases using both primary and recurrent tumors during and after denosumab treatment. In addition, to recognise morphological changes, immunohistochemical analysis of H3F3A and PDGFRβ was also performed. As an effect of denosumab treatment, the permanent absence of giant cells associated with severe to mild fibrosis was the most consistent morphological change, but H3F3A positive stromal/tumor cells were observed in all cases. Furthermore, an increased immunopositivity of PDGFRβ in stromal/tumor cells was evident in all recurrent cases during denosumab treatment. Upon tumor recurrence (after the discontinuation of denosumab treatment) the intensity of PDGFRβ immunostaining in stromal/tumor cells was restored/decreased. Our results confirm (for the first time) the activation of PDGFRβ on mononuclear stromal/tumor cells at protein level as an effect of denosumab treatment, which has so far only been demonstrated by phosphoprotein array analysis (protein lysates). The decreased PDGFRβ activity after the discontinuation of denosumab treatmeant and the increased PDGFRβ activity during denosumab treatment underlines the need for denosumab and sunitinib combination therapy.
C1 [Antal, Imre] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Papai, Zsuzsanna] Honved Korhaz, Onkologiai OsztalyBudapest, Hungary.
[Szendroi, Miklos] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Perlaky, Tamas] Semmelweis University, Department of OrthopedicsBudapest, Hungary.
[Dezso, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Lippai, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Sapi, Z (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM sapi.zoltan.dr@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610633
EP 1610640
DI 10.3389/pore.2022.1610633
PG 8
ER
PT J
AU Bang, S
Jee, S
Son, H
Cha, H
Sim, J
Kim, Y
Park, H
Myung, J
Kim, H
Paik, S
AF Bang, Seongsik
Jee, Seungyun
Son, Hwangkyu
Cha, Hyebin
Sim, Jongmin
Kim, Yeseul
Park, Hosub
Myung, Jaekyung
Kim, Hyunsung
Paik, Seungsam
TI Clinicopathological Implications of ASAP1 Expression in Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; prognosis; hepatocellular carcinoma; ArfGAP with SH3 domain ankyrin repeat and PH domain 1; ASAP1
ID immunohistochemistry; prognosis; hepatocellular carcinoma; ArfGAP with SH3 domain ankyrin repeat and PH domain 1; ASAP1
AB Background: The expression of ArfGAP with SH3 domain ankyrin repeat and PH domain 1 (ASAP1) is increased in various types of cancer, showing potential as a prognostic marker. The clinicopathological implications of ASAP1 expression in patients with hepatocellular carcinoma (HCC) remain unclear. We thus investigated the clinicopathological significance and prognostic effect of ASAP1 expression in HCC patients. Materials and Methods: ASAP1 expression was assessed in 149 HCC tissue samples using immunohistochemistry (IHC). The associations between ASAP1 expression and clinicopathological characteristics were analyzed. The prognostic effect of ASAP1 expression in patients with HCC was evaluated based on survival analyses and confirmed using a web-based tool. Results: ASAP1 expression was observed in the cytoplasm of tumor cells. High ASAP1 expression was observed in 89 (59.7%) of 149 cases. High ASAP1 expression was significantly associated with male patients (p = 0.018), higher histological grade (p = 0.013), vessel invasion (p = 0.021), and higher stage (p = 0.020). High ASAP1 expression was associated with shorter overall survival (OS; p = 0.041) and recurrence-free survival (RFS; p = 0.008) based on Kaplan-Meier survival analyses. Web-based analysis using Kaplan-Meier (KM) plotter showed high mRNA ASAP1 expression to be associated with short OS (p = 0.001). Conclusion: High ASAP1 expression was associated with aggressive clinicopathological characteristics and poor clinical outcomes in patients with HCC. ASAP1 can be considered a prognostic biomarker in HCC patients.
C1 [Bang, Seongsik] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Jee, Seungyun] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Son, Hwangkyu] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Cha, Hyebin] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Sim, Jongmin] Korea University College of Medicine, Anam Hospital, Department of PathologySeoul, South Korea.
[Kim, Yeseul] Korea University College of Medicine, Anam Hospital, Department of PathologySeoul, South Korea.
[Park, Hosub] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Myung, Jaekyung] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Kim, Hyunsung] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
[Paik, Seungsam] Seoul Hospital, Hanyang University College of Medicine, Department of PathologySeoul, South Korea.
RP Paik, S (reprint author), Seoul Hospital, Hanyang University College of Medicine, Department of Pathology, Seoul, South Korea.
EM sspaik@hanyang.ac.kr
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610635
EP 1610642
DI 10.3389/pore.2022.1610635
PG 8
ER
PT J
AU Zhu, Zz
Zhang, G
Liu, J
AF Zhu, Zhong-zhong
Zhang, Guanglin
Liu, Jianping
TI Establishment of a Novel Prognostic Prediction Model for Gastric Cancer Based on Necroptosis-Related Genes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; gastric cancer; treatment response; necroptosis
ID biomarker; prognosis; gastric cancer; treatment response; necroptosis
AB Background: Necroptosis plays a crucial role in the progression of multiple types of cancer. However, the role of necroptosis in gastric cancer (GC) remains unclear. The aim of this study is to establish a necroptosis-related prediction model, which could provide information for treatment monitoring. Methods: The TCGA-STAD cohort was employed to establish a prognostic prediction signature and the GEO dataset was employed for external validation. The correlation between the risk score and the immune landscape, tumor mutational burden (TMB), microsatellite instability (MSI), as well as therapeutic responses of different therapies were analyzed. Results: We constructed a prognostic model based on necroptosis-associated genes (NAGs), and its favorable predictive ability was confirmed in an external cohort. The risk score was confirmed as an independent determinant, and a nomogram was further established for prognosis. A high score implies higher tumor immune microenvironment (TIME) scores and more significant TIME cell infiltration. High-risk patients presented with lower TMB, and low-TMB patients had worse overall survival (OS). Meanwhile, Low-risk scores are characterized by MSI-high (MSI-H), lower Tumor Immune Dysfunction and Exclusion (TIDE) score, and higher immunogenicity in immunophenoscore (IPS) analysis. Conclusion: The developed NAG score provides a novel and effective method for predicting the outcome of GC as well as potential targets for further research.
C1 [Zhu, Zhong-zhong] Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi Central Hospital, Department of Gastroenteroanrectal SurgeryHuangshi, China.
[Zhang, Guanglin] Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi Central Hospital (Pu Ai Hospital), Department of Abdominal and Pelvic Medical Oncology II WardHuangshi, China.
[Liu, Jianping] Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi Central Hospital (Pu Ai Hospital), Department of Abdominal and Pelvic Medical Oncology II WardHuangshi, China.
RP Liu, J (reprint author), Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi Central Hospital (Pu Ai Hospital), Department of Abdominal and Pelvic Medical Oncology II Ward, Huangshi, China.
EM jianpl@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610641
EP 1610652
DI 10.3389/pore.2022.1610641
PG 12
ER
PT J
AU Takacs, F
Kotmayer, L
Czeti,
Szaloki, G
Laszlo, T
Mikala, G
Mark,
Masszi, A
Farkas, P
Plander, M
Weisinger, J
Demeter, J
Fekete, S
Szerafin, L
Deak, MB
Szaleczky, E
Sulak, A
Borbenyi, Z
Barna, G
AF Takacs, Ferenc
Kotmayer, Lili
Czeti, Agnes
Szaloki, Gabor
Laszlo, Tamas
Mikala, Gabor
Mark, Agnes
Masszi, Andras
Farkas, Peter
Plander, Mark
Weisinger, Julia
Demeter, Judit
Fekete, Sandor
Szerafin, Laszlo
Deak, Margit Beata
Szaleczky, Erika
Sulak, Adrienn
Borbenyi, Zita
Barna, Gabor
TI Revealing a Phenotypical Appearance of Ibrutinib Resistance in Patients With Chronic Lymphocytic Leukaemia by Flow Cytometry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE flow cytometry; targeted therapy; drug resistance; chronic lymphocytic leukaemia; ibrutinib
ID flow cytometry; targeted therapy; drug resistance; chronic lymphocytic leukaemia; ibrutinib
AB Background: Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to find phenotypic markers on CLL cells the expression of which may correlate with the appearance of ibrutinib resistance. Methods: We examined 28 patients’ peripheral blood (PB) samples (treatment naive, ibrutinib sensitive, clinically ibrutinib resistant). The surface markers’ expression (CD27, CD69, CD86, CD184, CD185) were measured by flow cytometry. Furthermore, the BTKC481S resistance mutation was assessed by digital droplet PCR. Moreover, the CLL cells’ phenotype of a patient with acquired ibrutinib resistance was observed during the ibrutinib treatment. Results: The expression of CD27 (p = 0.030) and CD86 (p = 0.031) became higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions were accompanied by BTKC481S mutation. Our prospective study showed that the increase of the expression of CD27, CD69 and CD86 was noticed ahead of the clinical resistance with 3 months. Conclusion: Our study suggests that the changes of the expression of these markers could indicate ibrutinib resistance and the examination of these phenotypic changes may become a part of the patients’ follow-up in the future.
C1 [Takacs, Ferenc] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Kotmayer, Lili] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Czeti, Agnes] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Szaloki, Gabor] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Laszlo, Tamas] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkohaz, Orszagos Hematologiai es Infektologiai Intezet (DPC-OHII)Budapest, Hungary.
[Mark, Agnes] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Masszi, Andras] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Farkas, Peter] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Plander, Mark] Vas County Markusovszky Hospital, Department of HematologySzombathely, Hungary.
[Weisinger, Julia] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Fekete, Sandor] Del-pesti Centrumkohaz, Orszagos Hematologiai es Infektologiai Intezet (DPC-OHII)Budapest, Hungary.
[Szerafin, Laszlo] Josa Andras County HospitalNyiregyhaza, Hungary.
[Deak, Margit Beata] National Institute of OncologyBudapest, Hungary.
[Szaleczky, Erika] National Institute of OncologyBudapest, Hungary.
[Sulak, Adrienn] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Borbenyi, Zita] University of Szeged, 2nd Department of Internal Medicine and Cardiology CentreSzeged, Hungary.
[Barna, Gabor] HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
RP Barna, G (reprint author), HCEMM-SE Molecular Oncohematology Research Group, Budapest, Hungary.
EM barna.gabor@med.semmelweis-univ.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610659
EP 1610665
DI 10.3389/pore.2022.1610659
PG 7
ER
PT J
AU Xu, Y
He, J
Li, W
Zhang, W
Liu, S
He, J
Pan, Z
Lu, Z
Peng, J
Lin, J
AF Xu, Yanbo
He, Jiarui
Li, Weihao
Zhang, Weili
Liu, Songran
He, Jiahua
Pan, Zhizhong
Lu, Zhenhai
Peng, Jianhong
Lin, Junzhong
TI The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE recurrence; colorectal cancer; prognosis; liver metastasis; pathologic complete response ratio
ID recurrence; colorectal cancer; prognosis; liver metastasis; pathologic complete response ratio
AB Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan–Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46–0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04–2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02–2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.
C1 [Xu, Yanbo] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[He, Jiarui] Sun Yat-sen University, Zhongshan School of MedicineGuangzhou, China.
[Li, Weihao] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[Zhang, Weili] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[Liu, Songran] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of PathologyGuangzhou, China.
[He, Jiahua] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of PathologyGuangzhou, China.
[Pan, Zhizhong] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[Lu, Zhenhai] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[Peng, Jianhong] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
[Lin, Junzhong] Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal SurgeryGuangzhou, China.
RP Lin, J (reprint author), Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Guangzhou, China.
EM linjzh@sysucc.org.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610663
EP 1610672
DI 10.3389/pore.2022.1610663
PG 10
ER
PT J
AU Kenessey, I
Szoke, G
Dobozi, M
Szatmari, I
Weber, A
Fogarassy, Gy
Nagy, P
Kasler, M
Polgar, Cs
Vathy-Fogarassy,
AF Kenessey, Istvan
Szoke, Georgina
Dobozi, Maria
Szatmari, Istvan
Weber, Andras
Fogarassy, Gyorgy
Nagy, Peter
Kasler, Miklos
Polgar, Csaba
Vathy-Fogarassy, Agnes
TI Comparison of Cancer Survival Trends in Hungary in the Periods 2001–2005 and 2011–2015 According to a Population-Based Cancer Registry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mortality; survival; incidence; oncology; cancer registry; trend
ID mortality; survival; incidence; oncology; cancer registry; trend
AB Background: Assessment of population-based cancer survival may provide the most valuable feedback about the effectiveness of oncological surveillance and treatment. Aims: Based on the database of the Hungarian National Cancer Registry, standardized incidence rates of lung, breast, colorectal, prostate and cervical cancer were compared to standardized mortality data of the Hungarian Central Statistical Office in the period between 2001 and 2015. Then survival analysis was performed on cleansed database. Results: The incidence of colorectal, breast and prostate cancer increased, while standardized rates of lung and cervical cancer declined. The survival of colorectal, breast and prostate cancer showed improvement. Contrarily, lung cancer exhibited a mild decline, while that of cervical cancer did not change significantly. In earlier stages survival was improved among almost every studied tumor type, while in advanced stages improvement was not observed. Comparison of stage distribution revealed that in the 2011–2015 period colorectal, breast and prostate cancer cases were diagnosed at earlier stages, while lung and cervical cancer patients were typically discovered at more advanced stages. Discussion: The outcome of advanced cancer treatments is better in earlier stages, which highlighted the importance of screening network. However, growth of oncological treatment costs with longer patient survival imposes a constantly increasing burden on society.
C1 [Kenessey, Istvan] National Institute of OncologyBudapest, Hungary.
[Szoke, Georgina] Pannon Egyetem, Rendszer- es Szamitastudomanyi TanszekVeszprem, Hungary.
[Dobozi, Maria] National Institute of OncologyBudapest, Hungary.
[Szatmari, Istvan] National Institute of OncologyBudapest, Hungary.
[Weber, Andras] National Institute of OncologyBudapest, Hungary.
[Fogarassy, Gyorgy] Allami Szivkorhaz, 1. Sz. Kardiologiai OsztalyBalatonfured, Hungary.
[Nagy, Peter] National Institute of OncologyBudapest, Hungary.
[Kasler, Miklos] National Institute of OncologyBudapest, Hungary.
[Polgar, Csaba] National Institute of OncologyBudapest, Hungary.
[Vathy-Fogarassy, Agnes] Pannon Egyetem, Rendszer- es Szamitastudomanyi TanszekVeszprem, Hungary.
RP Kenessey, I (reprint author), National Institute of Oncology, Budapest, Hungary.
EM steveken12@yahoo.com
CR Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2021, 71:209–49., DOI 10.3322/caac.21660
Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, et al. Cancer Incidence and Mortality Patterns in Europe: Estimates for 40 Countries and 25 Major Cancers in 2018. Eur J Cancer, 2018, 103:356–87., DOI 10.1016/j. ejca.2018.07.005
Arnold M, Rutherford MJ, Bardot A, Ferlay J, Andersson TM, Myklebust TA, et al. Progress in Cancer Survival, Mortality, and Incidence in Seven High- Income Countries 1995-2014, ICBP SURVMARK-2): a Population-Based Study. Lancet Oncol, 2019, 20:1493–505., DOI 10.1016/S1470-2045(19, 30456-5
Tusnady G, Gaudi I, Rejto L, Kasler M, Szentirmay Z. Survival Chances of Hungarian Cancer Patients in the National Cancer Registry. Magy Onkol, 2008, 52:339–49., DOI 10.1556/MOnkol.52.2008.4.2
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610668
EP 1610677
DI 10.3389/pore.2022.1610668
PG 10
ER
PT J
TI Corrigendum: Methylation Statuses of H19DMR and KvDMR at WT2 in Wilms Tumors in Taiwan
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE methylation; multiplex ligation-dependent probe amplification; Nephroblastoma; paternal uniparental disomy; Wilms tumor
ID methylation; multiplex ligation-dependent probe amplification; Nephroblastoma; paternal uniparental disomy; Wilms tumor
AB In the published article, there was an error in the Funding statement. The funding statement for the grant number from Chung Shan Medical University was displayed as “CSMU-INT-108-2.” The correct statement is “This work was supported by a grant from Chung Shan Medical University (grant number CSMU-INT-108-12).” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610677
EP 1610677
DI 10.3389/pore.2022.1610677
PG 1
ER
PT J
AU Timar, J
Uhlyarik, A
AF Timar, Jozsef
Uhlyarik, Andrea
TI On-Target Side Effects of Targeted Therapeutics of Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE immunotherapy; target therapy; bone therapy; angiogenesis inhibitor; side effect; pathomechanism
ID immunotherapy; target therapy; bone therapy; angiogenesis inhibitor; side effect; pathomechanism
AB The concept of precision medicine is based on the identification of hallmarks of cancer to exploit them as drug targets. The basic idea was that in this way the therapeutic modalities will be more effective and the side effects will be less. Since the majority of these novel modalities are not specific for a cancer-related biological process or a cancer-specific (mutant) target protein, it is not a surprise that we had to learn new type of side effects, because these therapeutics also affect physiological or pathological processes. Even more, in cases of some of these novel therapies we were able to discover new molecular mechanisms of physiological and pathological processes. Identification of the on-target side effects of targeted drugs can help to prevent the development of them or better manage the patients when emerge during cancer therapy.
C1 [Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Uhlyarik, Andrea] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM jtimar@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610694
EP 1610705
DI 10.3389/pore.2022.1610694
PG 12
ER
PT J
AU , PaORPO
AF , Pathology and Oncology Research Production Office
TI Erratum: The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE Symptomatic interval; Delayed diagnosis; CNS tumors; Survival outcome; pretreatment interval
ID Symptomatic interval; Delayed diagnosis; CNS tumors; Survival outcome; pretreatment interval
AB An Erratum on The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis by Barragan-Perez EJ, Altamirano-Vergara CE, Alvarez-Amado DE, Garcia-Beristain JC, Chico- Ponce-de-Leon F, Gonzalez-Carranza V, Juarez-Villegas L, Murata C (2020). Pathol. Oncol. Res. 26: 2693–2701. 10.1007/s12253-020-00875-3 Due to a production error at the previous publisher, the Supplementary Material in the original article incorrectly included a copy of the manuscript. The correct version of the Supplementary Material is published alongside this erratum. The original version of this article has not been updated.
C1 [, Pathology and Oncology Research Production Office] Frontiers Media SALausanne, Switzerland.
RP , PaORPO (reprint author), Frontiers Media SA, Lausanne, Switzerland.
EM production@por-journal.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD SEP
PY 2022
VL 28
IS 3
BP 1610756
EP 1610756
DI 10.3389/pore.2022.1610756
PG 1
ER
PT J
AU Huo, Q
Hu, J
Hou, B
Zhao, M
Han, X
Du, Y
Li, Y
AF Huo, Qi
Hu, Junjie
Hou, Binfen
Zhao, Mei
Han, Xue
Du, Yulin
Li, Yao
TI Clinicopathological Features and Prognostic Evaluation of UBR5 in Liver Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; TCGA; liver cancer; UBR5; YWHAZ
ID prognosis; TCGA; liver cancer; UBR5; YWHAZ
AB Background: Typically, liver cancer patients are diagnosed at an advanced stage and have a poor prognosis. N-recognin 5 (UBR5), a component of the ubiquitin protein ligase E3, is involved in the genesis and progression of several types of cancer. As of yet, it is unknown what the exact biological function of UBR5 is in liver cancer. Methods: A Kaplan-Meier survival curve (OS) was used to examine the effect of UBR5 expression on overall survival based on the TCGA database. To determine the molecular functions of UBR5 in liver cancer, we used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A protein-protein interaction (PPI) network was established for the screening of UBR5-related proteins in liver cancer. Western blot analysis was used to determine the expression levels of UBR5 and YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta), and in order to detect cell proliferation, an MTT assay was used. Results: The expression of UBR5 in liver cancer patient samples is significantly higher than in adjacent normal tissues. A high level of UBR5 expression was associated with older patients, a higher tumor grade, lymph node metastasis, and poor survival. We discovered YWHAZ with high connectivity, and UBR5 expression correlated positively with YWHAZ expression (r = 0.83, p < 0.05). Furthermore, we found that elevated UBR5 levels directly correlated with YWHAZ overexpression, and that UBR5 promoted cell proliferation by affecting YWHAZ expression. Additionally, the TCGA databases confirmed that patients with liver cancer who expressed higher levels of YWHAZ had poorer outcomes. Conclusion: This suggests that UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and that UBR5 may be a candidate treatment target for liver cancer. Therefore, UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and UBR5 could serve as a potential target for liver cancer treatment.
C1 [Huo, Qi] Bengbu Medical College, The Second Affiliated Hospital, Department of Medical OncologyBengbu, China.
[Hu, Junjie] Bengbu Medical College, The Second Affiliated Hospital, Department of Medical OncologyBengbu, China.
[Hou, Binfen] Bengbu Medical College, Department of Laboratory Medicine, Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and ImmunologyBengbu, China.
[Zhao, Mei] Bengbu Medical College, The Second Affiliated Hospital, Department of Medical OncologyBengbu, China.
[Han, Xue] Bengbu Medical College, Department of Laboratory Medicine, Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and ImmunologyBengbu, China.
[Du, Yulin] Bengbu Medical College, Department of Laboratory Medicine, Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and ImmunologyBengbu, China.
[Li, Yao] Bengbu Medical College, Department of Laboratory Medicine, Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and ImmunologyBengbu, China.
RP Li, Y (reprint author), Bengbu Medical College, Department of Laboratory Medicine, Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Bengbu, China.
EM liyao@bbmc.edu.cn
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Du G, Yu X, Chen Y, Cai W. MiR-1-3p Suppresses Colorectal Cancer Cell Proliferation and Metastasis by Inhibiting YWHAZ-Mediated Epithelial- Mesenchymal Transition. Front Oncol, 2021, 11:634596., DOI 10.3389/fonc. 2021.634596
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610396
EP 1610406
DI 10.3389/pore.2022.1610396
PG 11
ER
PT J
TI Overexpression of Dehydrogenase/ Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; rectal cancer; DHRS9; epithelial cell differentiation; keratan sulfate; mucin
ID biomarker; rectal cancer; DHRS9; epithelial cell differentiation; keratan sulfate; mucin
AB Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson’s chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610537
EP 1610546
DI 10.3389/pore.2022.1610537
PG 10
ER
PT J
AU Li, JJ
Wang, Sh
Guan, ZN
Zhang, JX
Zhan, RX
Zhu, JL
AF Li, Jin-Jin
Wang, Shuai
Guan, Zhong-Ning
Zhang, Jin-Xi
Zhan, Ri-Xin
Zhu, Jian-Long
TI Anterior Gradient 2 is a Significant Prognostic Biomarker in Bone Metastasis of Breast Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; bone metastasis; DEGs; BRCA; AGR2
ID prognosis; bone metastasis; DEGs; BRCA; AGR2
AB Background: The study aimed to detect DEGs associated with BRCA bone metastasis, filter prognosis biomarkers, and explore possible pathways. Methods: GSE175692 dataset was used to detect DEGs between BRCA bone metastatic cases and non-bone metastatic cases, followed by the construction of a PPI network among DEGs. The main module among the PPI network was then determined and pathway analysis on genes within the module was performed. Through performing Cox regression, Kaplan-Meier, nomogram, and ROC curve analyses using GSE175692 and GSE124647 datasets at the same time, the most significant prognostic biomarker was gradually filtered. Finally, important pathways associated with prognostic biomarkers were explored by GSEA analysis. Results: The 74 DEGs were detected between bone metastasis and non-bone metastasis groups. A total of 15 nodes were included in the main module among the whole PPI network and they mainly correlated with the IL-17 signaling pathway. We then performed Cox analysis on 15 genes using two datasets and only enrolled the genes with p < 0.05 in Cox analysis into the further analyses. Kaplan-Meier analyses using two datasets showed that the common biomarker AGR2 expression was related to the survival time ofBRCAmetastatic cases. Further, the nomogram determined the greatest contribution of AGR2 on the survival probability and the ROC curve revealed its optimal prognostic performance. More importantly, high expression of AGR2 prolonged the survival time of BRCA bone metastatic patients. These results all suggested the importance of AGR2 in metastatic BRCA. Finally, we performed the GSEA analysis and found that AGR2 was negatively related to IL-17 and NF-kβ signaling pathways. Conclusion: AGR2 was finally determined as the most important prognostic biomarker in BRCA bone metastasis, and it may play a vital role in cancer progression by regulating IL- 17 and NF-kB signaling pathways.
C1 [Li, Jin-Jin] Hangzhou Ninth People’s Hospital, Department of OrthopaedicsHangzhou, China.
[Wang, Shuai] Hangzhou Ninth People’s Hospital, Department of PathologyHangzhou, China.
[Guan, Zhong-Ning] Hangzhou Ninth People’s Hospital, Department of OrthopaedicsHangzhou, China.
[Zhang, Jin-Xi] Hangzhou Ninth People’s Hospital, Department of OrthopaedicsHangzhou, China.
[Zhan, Ri-Xin] Hangzhou Ninth People’s Hospital, Department of Medical Record ManagementHangzhou, China.
[Zhu, Jian-Long] Hangzhou Ninth People’s Hospital, Department of OrthopaedicsHangzhou, China.
RP Zhu, JL (reprint author), Hangzhou Ninth People’s Hospital, Department of Orthopaedics, Hangzhou, China.
EM XSSYZJL@163.com
CR Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2018, 68(6):394–424., DOI 10.3322/caac.21492
Weigelt B, Peterse JL, van ’t Veer LJ. Breast Cancer Metastasis: Markers and Models. Nat Rev Cancer, 2005, 5(8):591–602., DOI 10.1038/nrc1670
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610538
EP 1610550
DI 10.3389/pore.2022.1610538
PG 13
ER
PT J
AU Bencze, E
Bogos, K
Kohanka, A
Bathory-Fulop, L
Sarosi, V
Csernak, E
Bittner, N
Melegh, Zs
Toth, E
AF Bencze, Eszter
Bogos, Krisztina
Kohanka, Andrea
Bathory-Fulop, Laszlo
Sarosi, Veronika
Csernak, Erzsebet
Bittner, Nora
Melegh, Zsombor
Toth, Erika
TI EGFR T790M Mutation Detection in Patients With Non-Small Cell Lung Cancer After First Line EGFR TKI Therapy: Summary of Results in a Three-Year Period and a Comparison of Commercially Available Detection Kits
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE liquid biopsy; NSCLC; ctDNA; EGFR T790M mutation; AmoyDx super-ARMS EGFR mutation detection kit; cobas EGFR test v2
ID liquid biopsy; NSCLC; ctDNA; EGFR T790M mutation; AmoyDx super-ARMS EGFR mutation detection kit; cobas EGFR test v2
AB EGFR mutation in non-small cell lung cancer (NSCLC) offers a potential therapeutic target for tyrosine kinase inhibitor (TKI) therapy. The majority of these cases, however eventually develop therapy resistance, mainly by acquiring EGFR T790M mutation. Recently, thirdgeneration TKIs have been introduced to overcome T790M mutation-related resistance. Cell free circulating tumor DNA (liquid biopsy) has emerged as a valuable alternative method for T790M mutation detection during patient follow up, when a tissue biopsy cannot be obtained for analysis. In this study, we summarized our experience with Super- ARMS EGFR Mutation Detection Kit (AmoyDx) on 401 samples of 242 NSCLC patients in a 3-year period in Hungary, comprising 364 plasma and 37 non-plasma samples. We also compared the performance of two commercially available detection kits, the cobas EGFR Mutation test v2 (Roche) and the Super-ARMS EGFR Mutation Detection Kit (AmoyDx). The same activating EGFR mutation was detected with the AmoyDx kit as in the primary tumor in 45.6% of the samples. T790M mutation was identified in 48.1% of the samples containing activating EGFR mutation. The detection rate of T790M mutation was not dependent on the DNA concentration of the plasma sample and there was no considerable improvement in mutation detection rate after a second, subsequent plasma sample. The concordance of EGFR activating mutation detection was 89% between the two methods, while this was 93% for T790M mutation detection. The AmoyDx kit, however showed an overall higher detection rate of T790M mutation compared to the cobas kit (p = 0.014). T790M mutation was detected at 29.8% of the patients if only plasma samples were available for analysis, while the detection rate was 70.2% in non-plasma samples. If the activating EGFR was detected in the plasma samples, the detection rate of T790M mutation was 42.4%. Although non-plasma samples provided a superior T790M mutation detection rate, we found that liquid biopsy can offer a valuable tool for T790M mutation detection, when a tissue biopsy is not available. Alternatively, a liquid biopsy can be used as a screening test, when re-biopsy should be considered in case of wild-type results.
C1 [Bencze, Eszter] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Kohanka, Andrea] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
[Bathory-Fulop, Laszlo] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of MedicinePecs, Hungary.
[Csernak, Erzsebet] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
[Bittner, Nora] Semmelweis University, Department of OncologyBudapest, Hungary.
[Melegh, Zsombor] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
[Toth, Erika] National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular PathologyBudapest, Hungary.
RP Toth, E (reprint author), National Institute of Oncology, National Tumour Biology Laboratory, Department of Surgical and Molecular Pathology, Budapest, Hungary.
EM dr.toth.erika@oncol.hu
CR Bogos K, Kiss Z, Galffy G, Tamasi L, Ostoros G, Muller V, et al. Lung Cancer in Hungary. J Thorac Oncol, 2020, 15(5):692–9., DOI 10.1016/j.jtho.2019.11.001
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610607
EP 1610612
DI 10.3389/pore.2022.1610607
PG 6
ER
PT J
AU Yu, T
Yu, Shk
Lu, Kh
AF Yu, Tao
Yu, Shao-kun
Lu, Kai-hua
TI Comprehensive Molecular Analyses of an SLC Family-Based Model in Stomach Adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; prognosis; STAD; solute carrier; amino acid
ID immunotherapy; prognosis; STAD; solute carrier; amino acid
AB Background: Solute carrier (SLC) family members are crucial in transporting amino acids across membranes. Amino acids are indispensable for both cancer and immune cells. However, the clinical significance of amino acid transporting SLC members in stomach adenocarcinoma (STAD) remains unclear. This study aimed to develop an SLC familybased model to predict the prognosis and the response of STAD patients to immunotherapy. Methods: A total of 1239 tumor cases were obtained from online databases. The training set (n = 371) consisted of RNA sequencing profiles obtained from The Cancer Genome Atlas (TCGA), while those from Gene Expression Omnibus (GEO) were used as the test set. Subsequently, the clinical characteristics and immune profiles were investigated, and potential immunotherapy response prediction values of the model were assessed. Results: Based on the TCGA cohort, an SLC family-based model was developed using multivariate Cox analysis. All tumor cases were stratified into high- and low-risk groups considering the SLC model. High-risk patients had a worse overall survival (OS) than lowrisk patients, consistent with the results of GEO cohorts. Comprehensive analyses revealed that the high-risk group was correlated with aggressiveness-related pathways, whereas the low-risk group had better T helper cell infiltration and stronger immunotherapy response. Compared to the high-risk group, the low-risk group presented increased PD-L1 and tumor mutation burden. Conclusion: This SLC family-based model has the potential to predict the prognosis and immunotherapy outcomes of STAD patients. The survival of patients in the low-risk group was greatly prolonged, and the patients may benefit more from immunotherapy.
C1 [Yu, Tao] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
[Yu, Shao-kun] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
[Lu, Kai-hua] Nanjing Medical University, Hangzhou First People’s Hospital, Department of OncologyNanjing, China.
RP Lu, Kh (reprint author), Nanjing Medical University, Hangzhou First People’s Hospital, Department of Oncology, Nanjing, China.
EM lukaihua@njmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610610
EP 1610621
DI 10.3389/pore.2022.1610610
PG 12
ER
PT J
AU Ma, YT
Yang, HL
Yan, L
Hua, F
Wang, DG
Xu, GY
Li, Y
Xue, YJ
Qin, YJ
Sha, D
Ning, H
Zhao, MQ
Yao, ZG
AF Ma, Yu-Ting
Yang, Hong-Lan
Yan, Li
Hua, Fang
Wang, Dong-Guan
Xu, Guo-Ying
Li, Yan
Xue, Ying-Jie
Qin, Ye-Jun
Sha, Dan
Ning, Hao
Zhao, Miao-Qing
Yao, Zhi-Gang
TI Case Report: Potential Predictive Value of MMR/MSI Status and PD-1 Expression in Immunotherapy for Urothelial Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE immunotherapy; microsatellite instability; immune checkpoint inhibitors; urothelial carcinoma; lynch syndrome; PD-1/PD-L1
ID immunotherapy; microsatellite instability; immune checkpoint inhibitors; urothelial carcinoma; lynch syndrome; PD-1/PD-L1
AB Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability–high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LSassociated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.
C1 [Ma, Yu-Ting] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Yang, Hong-Lan] Dongying City People’s Hospital, Department of OncologyDongying, China.
[Yan, Li] Dongying City People’s Hospital, Department of PathologyDongying, China.
[Hua, Fang] Tulane University, Department of Microbiology and ImmunologyNew Orleans, LA, USA.
[Wang, Dong-Guan] Dongying City People’s Hospital, Department of PathologyDongying, China.
[Xu, Guo-Ying] Dongying Hospital of Traditional Chinese Medicine, Department of Urology SurgeryDongying, China.
[Li, Yan] Dongying City People’s Hospital, Department of OncologyDongying, China.
[Xue, Ying-Jie] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Qin, Ye-Jun] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Sha, Dan] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Ning, Hao] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of UrologyJinan, China.
[Zhao, Miao-Qing] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Yao, Zhi-Gang] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
RP Yao, ZG (reprint author), Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of Pathology, Jinan, China.
EM yzg20062009@163.com
CR De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, et al. Randomized Phase II/III Trial Assessing Gemcitabine/carboplatin and Methotrexate/carboplatin/vinblastine in Patients with Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986. J Clin Oncol, 2012, 30:191–9., DOI 10.1200/JCO.2011.37.3571
Galsky MD, Pal SK, Lin SW, Ogale S, Zivkovic M, Simpson J, et al. Real-World Effectiveness of Chemotherapy in Elderly Patients with Metastatic Bladder Cancer in the United States. Bladder Cancer, 2018, 4:227–38., DOI 10.3233/ BLC-170149
Rhea LP, Mendez-Marti S, Kim D, Aragon-Ching JB. Role of Immunotherapy in Bladder Cancer. Cancer Treat Res Commun, 2021, 26:100296., DOI 10.1016/j. ctarc.2020.100296
Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med, 2020, 383:2207–18., DOI 10.1056/NEJMoa2017699
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Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, et al. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit from PD-1/pd-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol, 2018, 36:1685–94., DOI 10.1200/JCO.2017.75.7740
Hodgson A, Vesprini D, Liu SK, Xu B, Downes MR. Correlation of Mismatch Repair Protein Deficiency, PD-L1 and CD8 Expression in High-Grade Urothelial Carcinoma of the Bladder. J Clin Pathol, 2020, 73:519–22., DOI 10.1136/jclinpath-2019-206256
Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, et al. Safety and Efficacy of Durvalumab, MEDI4736), an Anti-programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients with Advanced Urothelial Bladder Cancer. J Clin Oncol, 2016, 34:3119–25., DOI 10.1200/JCO.2016.67. 9761
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610638
EP 1610643
DI 10.3389/pore.2022.1610638
PG 6
ER
PT J
AU Zeng, J
Li, M
Dai, K
Zuo, B
Guo, J
Zang, L
AF Zeng, Jianmin
Li, Man
Dai, Kefan
Zuo, Bingyu
Guo, Jianhui
Zang, Lu
TI A Novel Glycolysis-Related Long Noncoding RNA Signature for Predicting Overall Survival in Gastric Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lncRNA; gastric cancer; TCGA; immune infiltration; prognostic signature
ID lncRNA; gastric cancer; TCGA; immune infiltration; prognostic signature
AB Background: The aim of this study was to construct a glycolysis-related long noncoding RNA (lncRNA) signature to predict the prognosis of patients with gastric cancer (GC). Methods: Glycolysis-related genes were obtained from the Molecular Signatures Database (MSigDB), lncRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas database (TCGA). Furthermore, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analysis were used to construct prognostic glycolysisrelated lncRNA signature. The specificity and sensitivity of the signature was verified by receiver operating characteristic (ROC) curves. We constructed a nomogram to predict the 1-year, 3-year, and 5-year survival rates of GC patients. Besides, the relationship between immune infiltration and the risk score was analyzed in the high and low risk groups. Multi Experiment Matrix (MEM) was used to analyze glycolysis-related lncRNA target genes. R “limma” package was used to analyze the mRNA expression levels of the glycolysis-related lncRNA target genes in TCGA. Gene set enrichment analysis (GSEA) was employed to further explore the biological pathways in the high-risk group and the glycolysis-related lncRNA target gene. Results: A prognostic signature was conducted based on nine glycolysis-related lncRNAs, which are AL391152.1, AL590705.3, RHOXF1-AS1, CFAP61-AS1, LINC00412, AC005165.1, AC110995.1, AL355574.1 and SCAT1. The area under the ROC curve (AUC) values at 1-year, 3-year, and 5-year were 0.765, 0.828 and 0.707 in the training set, and 0.669, 740 and 0.807 in the testing set, respectively. In addition, the nomogram could efficaciously predict the 1-year, 3-year, and 5-year survival rates of the GC patients. Then, we discovered that GC patients with high-risk scores were more likely to respond to immunotherapy. GSEA revealed that the signature was mainly associated with the calcium signaling pathway, extracellular matrix (ECM) receptor interaction, and focal adhesion in high-risk group, also indicated that SBSPON is related to aminoacyl-tRNA biosynthesis, citrate cycle, fructose and mannose metabolism, pentose phosphate pathway and pyrimidine metabolism. Conclusion: Our study shows that the signature can predict the prognosis of GC and may provide new insights into immunotherapeutic strategies.
C1 [Zeng, Jianmin] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of General SurgeryShanghai, China.
[Li, Man] The First Affiliated Hospital of Bengbu Medical CollegeBengbu, China.
[Dai, Kefan] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of General SurgeryShanghai, China.
[Zuo, Bingyu] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of General SurgeryShanghai, China.
[Guo, Jianhui] The Affiliated Hospital of Kunming University of Science and Technology, The First People’s Hospital of Yunnan Province, Second Department of General SurgeryKunming, China.
[Zang, Lu] Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of General SurgeryShanghai, China.
RP Zang, L (reprint author), Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of General Surgery, Shanghai, China.
EM zanglu@yeah.net
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610643
EP 1610656
DI 10.3389/pore.2022.1610643
PG 14
ER
PT J
AU Lovas, Sz
Al-Ali, ON
Varga, G
Szita, V
Alizadeh, H
Plander, M
Rajnics, P
Illes,
Szemlaky, Zs
Mikala, G
Varoczy, L
AF Lovas, Szilvia
Al-Ali, Obajed Nora
Varga, Gergely
Szita, Virag
Alizadeh, Hussain
Plander, Mark
Rajnics, Peter
Illes, Arpad
Szemlaky, Zsuzsa
Mikala, Gabor
Varoczy, Laszlo
TI Pomalidomide Treatment in Relapsed/ Refractory Multiple Myeloma Patients —Real-World Data From Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; toxicity; multiple myeloma; treatment response; pomalidomide
ID survival; toxicity; multiple myeloma; treatment response; pomalidomide
AB Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.
C1 [Lovas, Szilvia] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Al-Ali, Obajed Nora] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Varga, Gergely] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Szita, Virag] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Alizadeh, Hussain] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Plander, Mark] Vas County Markusovszky Hospital, Department of HematologySzombathely, Hungary.
[Rajnics, Peter] Kaposi Mor Teaching Hospital, Department of HematologyKaposvar, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Szemlaky, Zsuzsa] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Varoczy, L (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM varoczy@internal.med.unideb.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610645
EP 1610651
DI 10.3389/pore.2022.1610645
PG 7
ER
PT J
AU Zhang, B
Zhang, Y
Li, Q
Jiang, Q
Chu, W
Gong, H
Li, R
Ji, H
AF Zhang, Bing
Zhang, Yangyang
Li, Quan
Jiang, Qingjun
Chu, Wei
Gong, Haifeng
Li, Ruyuan
Ji, Hong
TI Case report: Chronic lymphocytic leukemia/small lymphocytic lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma: A composite lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; chronic lymphocytic leukemia; composite lymphoma; small lymphocytic lymphoma; monomorphic epitheliotropic intestinal T-cell lymphoma
ID case report; chronic lymphocytic leukemia; composite lymphoma; small lymphocytic lymphoma; monomorphic epitheliotropic intestinal T-cell lymphoma
AB Background: Composite lymphomas involving B-cell and T-cell lymphomas is very rare. Case presentation: We reported a 63-year-old gentleman with composite chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The patient was admitted to our hospital due to abdominal pain, and was diagnosed with CLL/SLL after bone marrow (BM) biopsy, BM aspiration, and flow cytometry. Two weeks later, he was diagnosed with MEITL based on pathological analysis after intestine excision. Next gene sequencing (NGS) findings identified two hotspot mutation sites (STAT5B and DNMT3A) closely related with the pathogenesis of CLL/SLL and MEILT. Additionally, BCOR mutation was only detected in the CLL/SLL area. The likely pathogenic mutations of CLL were SETD2, NOTCH1, SF3B1, and PTPN11, while the likely pathogenic mutations related with the MEILT were TET2 and ZRSR2. Mutations of GATA3, PLCG2, and FAT1 were identified in both CLL/SLL and MEITL areas, but the clinical significance was unknown. Finally, the patient died in the 12-month follow-up after surgery. Conclusion: We report a rare case of composite CLL/SLL and MEITL that highlights the importance of careful inspection of hematologic neoplasms. We also present the results of NGS of different gene mutations in CLL and MEITL tissues.
C1 [Zhang, Bing] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of UrologyQingdao, China.
[Zhang, Yangyang] Binzhou Medical University Hospital, Department of PathologyBinzhou, China.
[Li, Quan] Binzhou Medical University Hospital, Department of ImagingBinzhou, China.
[Jiang, Qingjun] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of ImagingQingdao, China.
[Chu, Wei] Binzhou Medical University Hospital, Department of PathologyBinzhou, China.
[Gong, Haifeng] Binzhou Medical University Hospital, Department of PathologyBinzhou, China.
[Li, Ruyuan] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of GastroenterologyQingdao, China.
[Ji, Hong] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of PathologyQingdao, China.
RP Ji, H (reprint author), Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of Pathology, Qingdao, China.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610653
EP 1610660
DI 10.3389/pore.2022.1610653
PG 8
ER
PT J
AU Polk, N
Budai, B
Hitre, E
Patocs, A
Mersich, T
AF Polk, Nandor
Budai, Barna
Hitre, Erika
Patocs, Attila
Mersich, Tamas
TI Corrigendum: High Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammation Index (SII) are Markers of Longer Survival After Metastasectomy of Patients With Liver-Only Metastasis of Rectal Cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE neutrophil-to-lymphocyte ratio; liver-only metastases of rectal cancer; metastasectomy; relapse-free survival; systemic immune-inflammation index; liver-only metastases of colon cancer; preoperative treatment
ID neutrophil-to-lymphocyte ratio; liver-only metastases of rectal cancer; metastasectomy; relapse-free survival; systemic immune-inflammation index; liver-only metastases of colon cancer; preoperative treatment
AB A Corrigendum on High Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammation Index (SII) are Markers of Longer Survival After Metastasectomy of Patients With Liver-Only Metastasis of Rectal Cancer by Polk N, Budai B, Hitre E, Patocs A and Mersich T (2022). Pathol. Oncol. Res. 28:1610315. doi: 10. 3389/pore.2022.1610315
C1 [Polk, Nandor] Orszagos Onkologiai Intezet, Emlo- es Lagyreszsebeszeti OsztalyBudapest, Hungary.
[Budai, Barna] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Hitre, Erika] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai OsztalyBudapest, Hungary.
[Patocs, Attila] Semmelweis University, Department of Laboratory MedicineBudapest, Hungary.
[Mersich, Tamas] Orszagos Onkologiai Intezet, Emlo- es Lagyreszsebeszeti OsztalyBudapest, Hungary.
RP Budai, B (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Budapest, Hungary.
EM budai.barna@oncol.hu
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610658
EP 1610659
DI 10.3389/pore.2022.1610658
PG 2
ER
PT J
AU Zhong, Z
Xu, M
Tan, J
AF Zhong, Zixuan
Xu, Minxuan
Tan, Jun
TI Identification of an Oxidative Stress-Related LncRNA Signature for Predicting Prognosis and Chemotherapy in Patients With Hepatocellular Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE hepatocellular carcinoma; survival analysis; immune cell infiltration; oxidative stress; drug sensitivity; lncRNA signature
ID hepatocellular carcinoma; survival analysis; immune cell infiltration; oxidative stress; drug sensitivity; lncRNA signature
AB Background: Oxidative stress plays a critical role in oncogenesis and tumor progression. However, the prognostic role of oxidative stress-related lncRNA in hepatocellular carcinomas (HCC) has not been fully explored. Methods: We used the gene expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify oxidative stress-related differentially expressed lncRNAs (DElncRNAs) by pearson correlation analysis. A four-oxidative stress-related DElncRNA signature was constructed by LASSO regression and Cox regression analyses. The predictive signature was further validated by Kaplan–Meier (K–M) survival analysis, receiver operating characteristic (ROC) curves, nomogram and calibration plots, and principal component analysis (PCA). Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the signature and immune status. Finally, the correlation between the signature and chemotherapeutic response of HCC patients was analyzed. Results: In our study, the four-DElncRNA signature was not only proved to be a robust independent prognostic factor for overall survival (OS) prediction, but also played a crucial role in the regulation of progression and chemotherapeutic response of HCC. ssGSEA showed that the signature was correlated with the infiltration level of immune cells. HCC patients in high-risk group were more sensitive to the conventional chemotherapeutic drugs including Sorafenib, lapatinib, Nilotinib, Gefitinib, Erlotinib and Dasatinib, which pave the way for targeting DElncRNA-associated treatments for HCC patients. Conclusion: Our study has originated a prognostic signature for HCC based on oxidative stress-related DElncRNAs, deepened the understanding of the biological role of four key DElncRNAs in HCC and laid a theoretical foundation for the choice of chemotherapy.
C1 [Zhong, Zixuan] Chongqing University of Education, School of Biological and Chemical Engineering, Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir RegionChongqing, China.
[Xu, Minxuan] Chongqing University of Education, School of Biological and Chemical Engineering, Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir RegionChongqing, China.
[Tan, Jun] Chongqing University of Education, School of Biological and Chemical Engineering, Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir RegionChongqing, China.
RP Zhong, Z (reprint author), Chongqing University of Education, School of Biological and Chemical Engineering, Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, Chongqing, China.
EM zhongzx@cque.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610670
EP 1610684
DI 10.3389/pore.2022.1610670
PG 15
ER
PT J
AU Ma, W
Zhang, X
Ma, Ch
Liu, P
AF Ma, Wanshan
Zhang, Xiaoning
Ma, Chenchen
Liu, Peng
TI Highly expressed FAM189B predicts poor prognosis in hepatocellular carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; hepatocellular carcinoma; clinical significance; FAM189B
ID biomarker; prognosis; hepatocellular carcinoma; clinical significance; FAM189B
AB Hepatocellular carcinoma (HCC) is one of the most malignant tumors with persistently high morbidity and mortality. However, the expression, prognostic and clinical significance of FAM189 family genes in HCC remain largely unknown. In this study, the expression levels of FAM189 family genes in HCC were analyzed through TCGA-LIHC and ICGC-LIRI-JP cohorts, and further validated in multiple independent GEO datasets. It was found that the expression of FAM189B was significantly upregulated in HCC tumor tissues, while the expression of FAM189A1 and FAM189A2 was not significantly changed between tumor and adjacent tissues. Further analysis revealed that upregulated copy number variation contributed to increased expression of FAM189B in HCC. Survival analysis showed that highly expressed FAM189B was significantly correlated with unfavorable prognosis, including overall survival, disease-specific survival, and progression-free interval. Univariate and multivariate Cox regression analysis showed that FAM189B was a potential novel prognosis factor for HCC patients. In addition, the association between FAM189B expression and clinical and molecular characteristics was analyzed. High expression of FAM189B was associated with high AFP level, high predicted risk metastasis signature, and TP53 mutation, while there was no significant association between FAM189B expression and cancer stage or tumor grade of HCC. Gene set enrichment analysis revealed that highly expressed FAM189B was closely related with signal pathways and biological processes associated with cell proliferation and cell cycle in HCC. In conclusion, this study suggested that FAM189B was highly expressed in HCC and highly expressed FAM189B may serve as an effective prognostic indicator and a potential therapeutic target for HCC patients.
C1 [Ma, Wanshan] Shandong Medicine and Health Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Department of Clinical Laboratory MedicineJinan, Shandong, China.
[Zhang, Xiaoning] Shandong Medicine and Health Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Department of Clinical Laboratory MedicineJinan, Shandong, China.
[Ma, Chenchen] Affiliated Hospital of Shandong University of Chinese Traditional Medicine, Central LaboratoryJinan, Shandong, China.
[Liu, Peng] Shandong Medicine and Health Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Department of Clinical Laboratory MedicineJinan, Shandong, China.
RP Liu, P (reprint author), Shandong Medicine and Health Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Department of Clinical Laboratory Medicine, Jinan, China.
EM summerivyleague@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610674
EP 1610687
DI 10.3389/pore.2022.1610674
PG 14
ER
PT J
AU Hiroe, T
Moriya, Sh
Kobayashi, S
Nishijima, Y
Watanabe, A
Shirabe, K
Ikota, H
Yokoo, H
Saio, M
AF Hiroe, Tamaki
Moriya, Shunichi
Kobayashi, Sayaka
Nishijima, Yoshimi
Watanabe, Akira
Shirabe, Ken
Ikota, Hayato
Yokoo, Hideaki
Saio, Masanao
TI Negative correlation between the nuclear size and nuclear Lamina component Lamin A in intraductal papillary mucinous neoplasms of the pancreas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Emerin; Lamin A; nuclear morphology; intraductal papillary mucinous neoplasm; computer-assisted image analysis
ID Emerin; Lamin A; nuclear morphology; intraductal papillary mucinous neoplasm; computer-assisted image analysis
AB Background: The nuclear laminar protein Lamin A and inner nuclear membrane protein Emerin plays important role in sustaining nuclear structure. However, They have not investigated the significance of these proteins for development of pancreatic intraductal papillary mucinous neoplasm (IPMN). Methods: We examined pancreatic IPMN specimens for nuclear morphology and nuclear protein expression pattern of Lamin A and Emerin. Forty-two IPMN specimens were included, with 30 classified as intraductal papillary mucinous adenoma (IPMA) and 12 as intraductal papillary mucinous carcinoma (IPMC). Results: Classification according to histological subtype revealed that 26 specimenswere of the gastric subtype (1 IPMC case), 8 were pancreatobiliary (6 IPMC cases), 6 were intestinal (3 IPMC cases), and 2 were oncocytic (all cases were IPMC). The frequency of IPMN subtypes in this study seemed to agree with those in previous reports. We analyzed Feulgen staining sections for nuclear morphological analysis using computer-assisted image analysis. Nuclear area and perimeter were significantly larger in IPMC than in IPMA. Finally, we examined the positive ratios of Lamin A and Emerin in immunohistochemical staining sections by image analysis. We found a negative correlation between the nuclear size and Lamin A-positive ratio, which was significantly lower in IPMC than that in IPMA. However, no significant correlation was observed between nuclear size and Emerin expression was observed, and no differences were found in the Emerin-positive ratio between IPMA and IPMC. Conclusion: Our results suggest that a decreased Lamin A positive ratio induces nuclear enlargement in adenomas, which thereby induce promotion to carcinomas. Furthermore, Lamin A expression can be a reliable biomarker for distinguishing between IPMC and IPMA.
C1 [Hiroe, Tamaki] Gunma University, Graduate School of Health Sciences, Department of Laboratory SciencesMaebashi, Gunma, Japan.
[Moriya, Shunichi] Gunma University, Graduate School of Health Sciences, Department of Laboratory SciencesMaebashi, Gunma, Japan.
[Kobayashi, Sayaka] Gunma University, Graduate School of Health Sciences, Department of Laboratory SciencesMaebashi, Gunma, Japan.
[Nishijima, Yoshimi] Gunma University, Graduate School of Health Sciences, Department of Laboratory SciencesMaebashi, Gunma, Japan.
[Watanabe, Akira] Gunma University, Graduate School of Medicine, Department of Hepatobiliary and Pancreatic SurgeryMaebashi, Gunma, Japan.
[Shirabe, Ken] Gunma University, Graduate School of Medicine, Department of Hepatobiliary and Pancreatic SurgeryMaebashi, Gunma, Japan.
[Ikota, Hayato] Gunma University Hospital, Clinical Department of PathologyMaebashi, Gunma, Japan.
[Yokoo, Hideaki] Gunma University, Graduate School of Medicine, Department of Human PathologyMaebashi, Gunma, Japan.
[Saio, Masanao] Gunma University, Graduate School of Health Sciences, Department of Laboratory SciencesMaebashi, Gunma, Japan.
RP Saio, M (reprint author), Gunma University, Graduate School of Health Sciences, Department of Laboratory Sciences, Maebashi, Japan.
EM saio@gunma-u.ac.jp
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Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: A consensus study. Virchows Arch, 2005, 447(5):794–9., DOI 10.1007/ s00428-005-0039-7
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610684
EP 1610696
DI 10.3389/pore.2022.1610684
PG 13
ER
PT J
AU He, K
Li, Ch
Yuan, H
Jiang, K
Deng, G
AF He, Kangwei
Li, Changjiu
Yuan, Hui
Jiang, Kang
Deng, Gang
TI Immunological role and prognostic value of SPARCL1 in pan-cancer analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; immune infiltration; pan-cancer; SPARCL1; M2 macrophage
ID prognosis; immune infiltration; pan-cancer; SPARCL1; M2 macrophage
AB Background: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) was a kind of extracellular matrix glycoprotein. SPARCL1 was strongly inhibited in most cancers. However, the potential functions of SPARCL1 in the pan-cancer cohort have not been widely studied. Methods: We evaluated the transcriptional level and the prognostic value of SPARCL1 in 33 types of cancer and revealed the relationship between genetic alterations of SPARCL1 and the tumor mutation burden. Meanwhile, we assessed the correlations between SPARCL1 and tumor-infiltrating lymphocytes across cancers. Results: The transcriptional level of SPARCL1 was inhibited in most cancers. Although SPARCL1 was down-regulated in most cancers, SPARCL1 might play a protective or detrimental role in different cancers. We demonstrated that mutation count was elevated in the altered SPARCL1 group in several cancers. Additionally, we found a significant positive correlation between SPARCL1 and macrophage infiltration levels in most cancers. Especially, marker sets of M2 macrophages were strongly related to SPARCL1 in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, and pancreatic adenocarcinoma. Conclusion: Our study found that SPARCL1 might work as a biomarker for prognosis and immune infiltration in pan-cancer analysis.
C1 [He, Kangwei] Zhejiang Chinese Medical University, The Fourth Clinical Medical CollegeHangzhou, China.
[Li, Changjiu] Zhejiang University, School of Medicine, The First Affiliated Hospital, Department of UrologyHangzhou, China.
[Yuan, Hui] Zhejiang Chinese Medical University, The Fourth Clinical Medical CollegeHangzhou, China.
[Jiang, Kang] Zhejiang University, School of Medicine, The First Affiliated Hospital, Department of UrologyHangzhou, China.
[Deng, Gang] Zhejiang University, School of Medicine, The First Affiliated Hospital, Department of UrologyHangzhou, China.
RP Deng, G (reprint author), Zhejiang University, School of Medicine, The First Affiliated Hospital, Department of Urology, Hangzhou, China.
EM dfg326@aliyun.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610687
EP 1610700
DI 10.3389/pore.2022.1610687
PG 14
ER
PT J
AU Ko, J
Jung, J
Kim, TS
Hong, YJ
Park, S
Park, OJ
Park, SY
Lim, YH
Kang, KW
Lee, J
AF Ko, Jihoon
Jung, Jaeyun
Kim, Tae Seung
Hong, Yong Jung
Park, Sehhoon
Park, Oh Joon
Park, Suk Young
Lim, Yeong Ho
Kang, Ki Won
Lee, Jeeyun
TI MET gene alterations predict poor survival following chemotherapy in patients with advanced cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE next-generation sequencing; oncogene; overall survival analysis; MET; MET alterations; chemotherapy; cancer
ID next-generation sequencing; oncogene; overall survival analysis; MET; MET alterations; chemotherapy; cancer
AB Background: To aid in oncology drug development, we investigated MET protooncogene receptor tyrosine kinase gene aberrations in 2,239 oncology patients who underwent next-generation sequencing (NGS) in clinical practice. Materials andmethods: FromNovember 2019 to January 2021, 2,239 patientswith advanced solid tumors who visited oncology clinics underwent NGS. The NGS panel included >500 comprehensive NGS tests using archival tissue specimens. Programmed death-ligand 1(PD-L1) 22C3 assay results and clinical records regarding initial chemotherapy were available for 1,137 (50.8%) and 1,761 (78.7%) patients, respectively for overall survival (OS) analysis. Results: The 2,239 patients represented 37 types of cancer. The NGS panel included >500 genes, microsatellite instability status, tumor mutational burden, and fusions. Themost commoncancer types were colorectal (N=702),gastric (N= 481), and sarcoma (N = 180). MET aberrations were detected in 212 patients. All MET-amplified tumors had microsatellite stable status, and 8 had a high tumor mutational burden.Of 46 patientswithMET-amplified cancers, 8 had MET-positive protein expression by immunohistochemistry (2+ and 3+). MET fusion was detected in 10 patients. Partner genes of MET fusion included ST7, TFEC, LRRD1, CFTR, CAV1, PCM1, HLA-DRB1, and CAPZA2. In survival analysis, patients with amplification of MET gene fusion had shorter OS and progressionfree survival (PFS) than thosewithout. Thus, MET aberrationwas determined to be a factor of response to chemotherapy. Conclusion: Approximately 2.1% and 0.4% of patients with advanced solid tumors demonstrated MET gene amplification and fusion, respectively, and displayed a worse response to chemotherapy and significantly shorter OS and PFS than those without MET gene amplification or fusion.
C1 [Ko, Jihoon] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Jung, Jaeyun] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Kim, Tae Seung] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Hong, Yong Jung] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Park, Sehhoon] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Park, Oh Joon] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Park, Suk Young] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Lim, Yeong Ho] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Kang, Ki Won] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
[Lee, Jeeyun] Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-OncologySeoul, South Korea.
RP Lee, J (reprint author), Sungkyunkwan University, School of Medicine, Samsung Medical Center, Department of Medicine, Division of Hematology-Oncology, Seoul, South Korea.
EM jyunlee@skku.edu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610697
EP 1610706
DI 10.3389/pore.2022.1610697
PG 10
ER
PT J
AU Huang, Q
Shen, YJ
Hsueh, ChY
Zhang, YF
Yuan, XH
Zhou, YJ
Li, JY
Lin, L
Wu, ChP
Hu, ChY
AF Huang, Qiang
Shen, Yu-Jie
Hsueh, Chi-Yao
Zhang, Yi-Fan
Yuan, Xiao-Hui
Zhou, Yu-Juan
Li, Jiao-Yu
Lin, Lan
Wu, Chun-Ping
Hu, Chun-Yan
TI Plasma Extracellular Vesicles-Derived miR-99a-5p: A Potential Biomarker to Predict Early Head and Neck Squamous Cell Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; HNSCC; HPV; plasma extracellular vesicles; miR-99a-5p
ID biomarker; HNSCC; HPV; plasma extracellular vesicles; miR-99a-5p
AB Purpose: This study aimed to investigate the applicability of plasma extracellular vesicles (EVs) miR-99a-5p as a potential head and neck squamous cell carcinoma (HNSCC) diagnostic biomarker. Methods: The miRNA expression of HNSCC tissue and plasma EVs were profiled by small RNA sequencing. qRT-PCR was performed to detect miR-99a-5p expression in HNSCC (n = 93) and benign disease (n = 39) plasma EVs and formalin-fixed and paraffinembedded (FFPE) tissue (n = 110). We constructed receiver-operating characteristic curves to investigate the diagnostic efficiency of plasma EVs miR-99a-5p. Results: Tumor tissue exhibited lower miR-99a-5p than para-tumor tissue. Patients with high miR-99a-5p expression exhibited significantly more p16 positive status. In contrast, HNSCC plasma EVs harbored more miR-99a-5p than the benign disease group. Plasma EVs miR-99a-5p distinguished HNSCC with area under the curve (AUC) of 0.7494 (95% CI: 0.6692–0.8296; p < 0.0001), with 61.54% sensitivity and 75.27% specificity, respectively. Furthermore, plasma EVs miR-99a-5p also distinguished early HNSCC with AUC of 0.7394 (95% CI: 0.6284–0.8504; p = 0.0002), with 79.07% sensitivity and 61.54% specificity, respectively. Conclusion: Plasma EVs miR-99a-5p is a potential biomarker for predicting early HNSCC.
C1 [Huang, Qiang] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Shen, Yu-Jie] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Hsueh, Chi-Yao] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Zhang, Yi-Fan] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Yuan, Xiao-Hui] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Zhou, Yu-Juan] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Li, Jiao-Yu] Shanghai Jiaotong University School of Medicine, Xinhua Hospital, Department of PediatricShanghai, China.
[Lin, Lan] Fudan University, Eye & ENT Hospital, Department of PathologyShanghai, China.
[Wu, Chun-Ping] Fudan University, Eye & ENT Hospital, Department of OtorhinolaryngologyShanghai, China.
[Hu, Chun-Yan] Fudan University, Eye & ENT Hospital, Department of PathologyShanghai, China.
RP Hu, ChY (reprint author), Fudan University, Eye & ENT Hospital, Department of Pathology, Shanghai, China.
EM huchy2003@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610699
EP 1610708
DI 10.3389/pore.2022.1610699
PG 10
ER
PT J
AU Xiong, S
Jin, L
Zeng, Ch
Ma, H
Xie, L
Liu, Sh
AF Xiong, Siping
Jin, Long
Zeng, Chao
Ma, Hongmei
Xie, Linying
Liu, Shuguang
TI An innovative pyroptosis-related long-noncoding-RNA signature predicts the prognosis of gastric cancer via affecting immune cell infiltration landscape
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; gastric cancer; pyroptosis; overall survival; lncRNA signature
ID prognosis; gastric cancer; pyroptosis; overall survival; lncRNA signature
AB Background: Gastric cancer (GC) is a worldwide popular malignant tumor. However, the survival rate of advanced GC remains low. Pyroptosis and long non-coding RNAs (lncRNAs) are important in cancer progression. Thus, we aimed to find out a pyroptosis-related lncRNAs (PRLs) signature and use it to build a practical risk model with the purpose to predict the prognosis of patients with GC. Methods: Univariate Cox regression analysis was used to identify PRLs linked to GC patient’s prognosis. Subsequently, to construct a PRLs signature, the least absolute shrinkage and selection operator regression, and multivariate Cox regression analysis were used. Kaplan–Meier analysis, principal component analysis, and receiver operating characteristic curve analysis were performed to assess our novel lncRNA signature. The correlation between risk signature and clinicopathological features was also examined. Finally, the relationship of pyroptosis and immune cells were evaluated through the CIBERSORT tool and single-sample lncRNA set enrichment analysis (ssGSEA). Results: A PRLs signature comprising eight lncRNAs was discerned as a selfdetermining predictor of prognosis. GC patients were sub-divided into high-risk and low-risk groups via this risk-model. Stratified analysis of different clinical factors also displayed that the PRLs signature was a good prognosis factor. According to the risk score and clinical characteristics, a nomogram was established. Moreover, the difference between the groups is significance in immune cells and immune pathways. Conclusion: This study established an effective prognostic signature consist of eight PRLs in GC, and constructed an efficient nomogram model. Further, the PRLs correlated with immune cells and immune pathways.
C1 [Xiong, Siping] Sun Yat-sen University, The Eighth Affiliated Hospital, Department of PathologyShenzhen, Guangdong, China.
[Jin, Long] Fujian Medical University, Shengli Clinical Medical College, Department of PathologyFuzhou, Fujian, China.
[Zeng, Chao] Sun Yat-sen University, The Eighth Affiliated Hospital, Department of PathologyShenzhen, Guangdong, China.
[Ma, Hongmei] Sun Yat-sen University, The Eighth Affiliated Hospital, Department of PathologyShenzhen, Guangdong, China.
[Xie, Linying] Sun Yat-sen University, The Eighth Affiliated Hospital, Department of PathologyShenzhen, Guangdong, China.
[Liu, Shuguang] Sun Yat-sen University, The Eighth Affiliated Hospital, Department of PathologyShenzhen, Guangdong, China.
RP Liu, Sh (reprint author), Sun Yat-sen University, The Eighth Affiliated Hospital, Department of Pathology, Shenzhen, China.
EM liushg3@mail.sysu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610712
EP 1610726
DI 10.3389/pore.2022.1610712
PG 15
ER
PT J
AU Paszt, A
Ottlakan, A
Abraham, Sz
Simonka, Zs
Vas, M
Maraz, A
Szepes, Z
Tiszlavicz, L
Nyari, T
Olah, J
Lazar, Gy
AF Paszt, Attila
Ottlakan, Aurel
Abraham, Szabolcs
Simonka, Zsolt
Vas, Marton
Maraz, Aniko
Szepes, Zoltan
Tiszlavicz, Laszlo
Nyari, Tibor
Olah, Judit
Lazar, Gyorgy
TI Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE surgery; chemoradiotherapy; neoadjuvant treatment; capecitabine; advanced rectal cancer
ID surgery; chemoradiotherapy; neoadjuvant treatment; capecitabine; advanced rectal cancer
AB Background: During the last decade, one of the most important treatment options for locally advanced, potencially resectable rectal tumours was neoadjuvant chemoradiotherapy (CRT) followed by surgery. Methods: Effects of the neoadjuvant treatment on surgical outcomes were retrospectively analysed in 185 patients with stage T2–T4 and N0–2, resectable rectal tumour among two patient groups defined by radiosensitizer agents. Group 1 (n = 94) involved radiotherapy (RT) with 50.4 Gy total dose (25 × 1.8 Gy + 3 × 1.8 Gy tumour bed boost), and intravenous 5-fluorouracil (5-FU) (350 mg/ m2) with leucovorin (20 mg/m2) on the 1–5 and 21–25 days, while Group 2 (n = 91) RT and orally administrated capecitabine (daily 2 × 825 mg/m2) on RT days. Surgery was carried out after 8–10 weeks. Side effects, perioperative complications, type of surgery, number of removed regional lymph nodes, resection margins and tumour regression grade (TRG) were analysed. Results: More favourable side effects were observed in Group 2. Despite the same rate of diarrhoea (Group 1 vs. Group 2: 54.3% vs. 56.0%), Grade 2–3 diarrhoea ratio was lower (p = 0.0352) after capecitabine (Group 2). Weight loss occurred in 17.0% and 2.2% (p = 0.00067), while nausea and vomiting was described in 38.3% and 15.4% (p = 0.00045) with 5-FU treatment and capecitabine respectively. Anaemia was observed in 33.0% and 22.0% (p = 0.0941). Complete tumour regression occurred in 25.3% after oral- and 13.8% after intravenous treatment (p = 0.049). Ratio of sphincter preservation was higher with laparoscopy than open surgery (72.3% vs. 39.7%) (p = 0.00001). Conclusion: The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and overall clinical outcome, with increased rate of complete tumour regression.
C1 [Paszt, Attila] University of Szeged, Department of SurgerySzeged, Hungary.
[Ottlakan, Aurel] University of Szeged, Department of SurgerySzeged, Hungary.
[Abraham, Szabolcs] University of Szeged, Department of SurgerySzeged, Hungary.
[Simonka, Zsolt] University of Szeged, Department of SurgerySzeged, Hungary.
[Vas, Marton] University of Szeged, Department of SurgerySzeged, Hungary.
[Maraz, Aniko] University of Szeged, Department of OncotherapySzeged, Hungary.
[Szepes, Zoltan] University of Szeged, 1st Department of MedicineSzeged, Hungary.
[Tiszlavicz, Laszlo] University of Szeged, Department of PathologySzeged, Hungary.
[Nyari, Tibor] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Olah, Judit] University of Szeged, Department of OncotherapySzeged, Hungary.
[Lazar, Gyorgy] University of Szeged, Department of SurgerySzeged, Hungary.
RP Paszt, A (reprint author), University of Szeged, Department of Surgery, Szeged, Hungary.
EM paszt.attila@med.u-szeged.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610722
EP 1610732
DI 10.3389/pore.2022.1610722
PG 11
ER
PT J
AU Yang, L
Fan, Y
Lu, H
AF Yang, Lan
Fan, Ying
Lu, Hongyang
TI Pulmonary Large Cell Neuroendocrine Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE treatment; diagnosis; LCNEC; imaging examination; pathologic features; prognosis
ID treatment; diagnosis; LCNEC; imaging examination; pathologic features; prognosis
AB Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of malignant pulmonary tumor. The incidence rate of LCNEC was reported to be 0.3%–3% in lung cancers. Although LCNEC is classified as non-small cell lung cancer (NSCLC), it is more aggressive and malignant than other NSCLC, and its biological behavior is similar to that of small cell lung cancer (SCLC). Most of the LCNEC patients are elderly smoking male and the clinical manifestations are not specific. The imaging manifestations of the tumors are often located in the periphery and the upper lobes, and the enlargement of mediastinal or hilar lymph nodes is common. The diagnosis is mainly based on pathology by the histological features and immunohistochemistry (IHC). Specific neuroendocrine markers such as chromogranin A (CgA), synaptophysin (Syn) and CD56 are usually diffusely positive in LCNEC, and found that insulinoma-associated protein (INSM1) and high rate of Ki-67 are helpful for diagnosis. More differential diagnoses also increase the difficulty of correctly diagnosing LCNEC. The rise of LCNEC molecular typing in recent years may be helpful for diagnosis and subsequent treatment. This review focuses on the epidemiological features, imaging studies, pathology, diagnosis, treatment, and prognosis of LCNEC.
C1 [Yang, Lan] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
[Fan, Ying] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
[Lu, Hongyang] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
RP Lu, H (reprint author), Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, China.
EM luhy@zjcc.org.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610730
EP 1610740
DI 10.3389/pore.2022.1610730
PG 11
ER
PT J
AU Wang, LJ
Liu, L
Ju, W
Yao, WX
Yang, XH
Qian, WH
AF Wang, Li-Jun
Liu, Liu
Ju, Wei
Yao, Wen-Xin
Yang, Xi-Hu
Qian, Wen-Hao
TI 20 abnormal metabolites of Stage IV Grade C periodontitis was discovered by CPSI-MS
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE metabolomics; point-of-care test; conducting polymer spray ionization; saliva metabolomics; severe periodontitis (Stage IV and Grade C)
ID metabolomics; point-of-care test; conducting polymer spray ionization; saliva metabolomics; severe periodontitis (Stage IV and Grade C)
AB Saliva is a noninvasive biofluid that contains the metabolic signature of severe periodontitis (SP, Stage IV and Grade C). Conductive polymer spray ionization mass spectrometry (CPSI-MS) was used to record a wide range of metabolites within a few seconds, making this technique a promising point-of-care method for the early detection of SP (Stage IV and Grade C). Saliva samples from 31 volunteers, consisting of 16 healthy controls (HC) and 15 patients with SP (Stage IV and Grade C), were collected to identify dysregulated metabolites. Twenty metabolites were screened out, including seven amino acids. Moreover, the results showed that amino acid metabolism is closely related to the development of periodontitis. The present study further confirmed that salivary metabolites in the oral cavity were significantly altered after plaque removal. These results suggest that the combination of CPSI-MS is a feasible tool for preclinical screening of SP (Stage IV and Grade C).
C1 [Wang, Li-Jun] Xuhui District Dental Center, Department of PeriodontitisShanghai, China.
[Liu, Liu] Shanghai Jiao Tong University School of Medicine, Ninth People’s Hospital, Department of Oral and Maxillofacial-Head & Neck OncologyShanghai, China.
[Ju, Wei] Affiliated Hospital of Jiangsu University, Department of Oral and Maxillofacial SurgeryZhenjiang, Jiangsu, China.
[Yao, Wen-Xin] Xuhui District Dental Center, Department of PeriodontitisShanghai, China.
[Yang, Xi-Hu] Affiliated Hospital of Jiangsu University, Department of Oral and Maxillofacial SurgeryZhenjiang, Jiangsu, China.
[Qian, Wen-Hao] Xuhui District Dental Center, Department of PeriodontitisShanghai, China.
RP Qian, WH (reprint author), Xuhui District Dental Center, Department of Periodontitis, Shanghai, China.
EM pingyanlaoto@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610739
EP 1610746
DI 10.3389/pore.2022.1610739
PG 8
ER
PT J
AU Susztak, N
Besznyak, I
Almasi, K
Bursics, A
Kelemen, D
Borowski, D
Banky, B
AF Susztak, Nora
Besznyak, Istvan
Almasi, Kalman
Bursics, Attila
Kelemen, Dora
Borowski, W. David
Banky, Balazs
TI Improved Accuracy of Lymph Node Staging and Long-Term Survival Benefit in Colorectal Cancer With Ex Vivo Arterial Methylene Blue Infiltration
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; overall survival; methylene blue; nodal staging accuracy; lymph node staging
ID colorectal cancer; overall survival; methylene blue; nodal staging accuracy; lymph node staging
AB Introduction: Ex vivo methylene blue (MB) injection into the main supplying arteries of the colorectal specimen after surgical removal is an uncomplicated technique to support lymph node harvest during pathological evaluation. The primary aim of this randomized, interventional, bicentric trialwas to evaluate the impact ofMB injection on lymph node yield, with secondary aims assessing the accuracy of lymph node staging and the effect on 5- year overall survival for patients undergoing resection of colorectal cancer. Methods: In the study period between December 2013 and August 2015, 200 colorectal resections were performed at two independent onco-surgery centers of Hungary. Following surgical resection, each specimen was randomly assigned either to the control (standard pathological work-up) or to the MB staining group before formaldehyde fixation. Patient-level surgical and clinical data were retrieved from routinely collected clinical datasets. Survival status data were obtained from the National Health Insurance Fund of Hungary. Results: A total of 162 specimens, 82 in the control and 80 in the MB groups, were included for analysis. Baseline characteristics were equally distributed among study groups, except for specimen length. Both the median of total number of lymph nodes retrieved (control 11 ± 8 [0–33] nodes vs. MB 14 ± 6 [0–42] nodes; p < 0.01), and the ratio of cases with at least 12 removed lymph nodes (36/82, 43.9% vs. 53/80, 66.3%; p < 0.01) were higher in the MB group. The rate of accurate lymph node staging was nonsignificantly improved. As for rectal cancer, nodal staging accuracy (16/31, 51.6% vs. 23/30, 76.7%; p = 0.04) and the proportion with minimum 12 lymph node retrieval (7/31, 22.6%, vs. 18/30, 60%; p < 0.01) was improved by MB injection. In Mantel–Cox regression, a statistically significant survival benefit with methylene blue injection at 5 years post-surgery was proven (51.2% vs. 68.8%; p = 0.04). Conclusion: In our experience, postoperative ex vivo arterial methylene blue injection appears to be an uncomplicated technique, improving lymph node yield and decreasing the chance of insufficient nodal staging. The technique might also associate with a 5-year overall survival benefit.
C1 [Susztak, Nora] Semmelweis University, Faculty of MedicineBudapest, Hungary.
[Besznyak, Istvan] Fovarosi Onkormanyzat Uzsoki utcai Oktato Korhaz, Sebeszeti-Ersebeszeti OsztalyBudapest, Hungary.
[Almasi, Kalman] Petz Aladar Hospital, Department of PathologyGyor, Hungary.
[Bursics, Attila] Fovarosi Onkormanyzat Uzsoki utcai Oktato Korhaz, Sebeszeti-Ersebeszeti OsztalyBudapest, Hungary.
[Kelemen, Dora] Fovarosi Uzsoki utcai Korhaz, PathologiaBudapest, Hungary.
[Borowski, W. David] Welwitschia Hospital, Department of SurgeryWalvis Bay, Namibia.
[Banky, Balazs] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
RP Susztak, N (reprint author), Semmelweis University, Faculty of Medicine, Budapest, Hungary.
EM nsusztak@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610742
EP 1610751
DI 10.3389/pore.2022.1610742
PG 10
ER
PT J
AU Li, M
Yang, L
Lu, H
AF Li, Meihui
Yang, Lan
Lu, Hongyang
TI Pulmonary Combined Large Cell Neuroendocrine Carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE pulmonary combined large cell neuroendocrine carcinoma (CLCNEC); pathological characteristics; diagnosis; therapy; targeted therapy
ID pulmonary combined large cell neuroendocrine carcinoma (CLCNEC); pathological characteristics; diagnosis; therapy; targeted therapy
AB Pulmonary combined large-cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine tumor pertained to lung large cell neuroendocrine carcinoma (LCNEC) with aggressive behavior and poor prognosis generally. The clinical features of CLCNEC are not specific including cough, expectoration, chest distress, chest pain, etc., which are prone to have different manifestations of the mixed components. Owing to the low incidence, there are few related smallscale retrospective studies and case reports. Currently, the treatment regimen of CLCNEC mainly refers to LCNEC that complete surgical resection is preferred in the early stage and according to previous researches, platinumbased small cell lung cancer (SCLC) standard treatment regimen showed promising results in postoperative and advanced CLCNEC as compared to that of non-small cell lung cancer (NSCLC). Adenocarcinoma-CLCNEC more likely harbor driver gene mutation, and may benefit from targeted therapy. As for immunotherapy, more clinical trial data are needed to support its benefits. This article will fill the gap and will provide new insight into the clinical characteristics, pathological diagnosis and treatment endeavors of CLCNEC.
C1 [Li, Meihui] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
[Yang, Lan] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
[Lu, Hongyang] Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus)Hangzhou, China.
RP Lu, H (reprint author), Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, China.
EM luhy@zjcc.org.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610747
EP 1610752
DI 10.3389/pore.2022.1610747
PG 6
ER
PT J
AU Wang, H
Xie, H
Wang, Sh
Zhao, J
Gao, Y
Chen, J
Zhao, Y
Guo, G
AF Wang, Hetong
Xie, Haitao
Wang, Shuying
Zhao, Jiaying
Gao, Ya
Chen, Jun
Zhao, Yuxia
Guo, Genyan
TI PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiotherapy; polymorphism; non-small cell lung cancer (NSCLC); PARP-1; sensitivity
ID radiotherapy; polymorphism; non-small cell lung cancer (NSCLC); PARP-1; sensitivity
AB About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome.
C1 [Wang, Hetong] The Tenth People’s Hospital of Shenyang, Department of Radiation OncologyShenyang, China.
[Xie, Haitao] Liaoning Cancer Hospital, Department of Radiation OncologyShenyang, China.
[Wang, Shuying] Shandong Polytechnic CollegeJining, China.
[Zhao, Jiaying] Qingdao United Family Healthcare, Department of Radiation OncologyQingdao, China.
[Gao, Ya] Kailuan Hospital, Department of OncologyTangshan, Hebei, China.
[Chen, Jun] The Tenth People’s Hospital of Shenyang, Department of Radiation OncologyShenyang, China.
[Zhao, Yuxia] The Fourth Affiliated Hospital of China Medical University, Department of Radiation OncologyShenyang, China.
[Guo, Genyan] The Fourth Affiliated Hospital of China Medical University, Department of Radiation OncologyShenyang, China.
RP Guo, G (reprint author), The Fourth Affiliated Hospital of China Medical University, Department of Radiation Oncology, Shenyang, China.
EM gyguo@cmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610751
EP 1610757
DI 10.3389/pore.2022.1610751
PG 7
ER
PT J
AU AlQudah, M
Khalifeh, M
Al-Azaizeh, R
Masaadeh, A
Al-Rusan, O
Haddad, H
AF AlQudah, Mohammad
Khalifeh, Mohammad
Al-Azaizeh, Rasha
Masaadeh, Amr
Al-Rusan, M. Omar
Haddad, K. Husam
TI Hyperbaric oxygen exposure alleviate metabolic side-effects of olanzapine treatment and is associated with Langerhans islet proliferation in rats
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE olanzapine; hyperbaric oxygen therapy; pancreatic Langerhans cells; metabolic disorders; insulin
ID olanzapine; hyperbaric oxygen therapy; pancreatic Langerhans cells; metabolic disorders; insulin
AB Introduction: Olanzapine (OLZ) is one of the second-generation antipsychotics drugs (APDs) used to treat several psychiatric illnesses. Olanzapine treatment is often associated with many metabolic side effects in a dose dependent manner such as obesity, dyslipidemia and insulin resistance, induction of type II diabetes and acute pancreatitis in some patients. Methods: Hyperbaric Oxygen therapy (HBOT) was investigated as a tool to mitigate olanzapine metabolic side effects in rats. Thirty-six female Sprague Dawley (SD) rats were divided into 4 groups; rats on olanzapine treatment either exposed to hyperbaric oxygen therapy (HBOOLZ) or left without exposure (OLZ) then non-treated rats that either exposed to hyperbaric oxygen therapy or left without exposure (control). Rats received Hyperbaric Oxygen therapy for 35 days at 2.4 atmospheres absolute (ATA) for 2.5 h daily followed by intraperitoneal injection of olanzapine at 10mg/kg or placebo. Results: Rats on either hyperbaric oxygen therapy or olanzapine had a significant loss in body weight. Olanzapine treatment showed a decrease in serum insulin level, triglyceride, highdensity lipoprotein (HDL) cholesterol, and lipase level but an increase in fasting blood sugar (FBS), insulin resistance index (HOMA-IR) and amylase, while rats’ exposure to hyperbaric oxygen therapy reversed these effects. The Pancreatic Langerhans islets were up-regulated in both hyperbaric oxygen therapy and olanzapine treatments but the combination (HBOOLZ) doubled these islets number. Discussion: This study advocated that hyperbaric oxygen therapy can be an alternative approach to control or reverse many metabolic disorders (MDs) associatedwith olanzapine treatment. In addition, it seems that hyperbaric oxygen therapy positively affect the pancreatic Langerhans cells activity and architecture.
C1 [AlQudah, Mohammad] Jordan University of Science and Technology, Faculty of Medicine, Department of Pathology and MicrobiologyIrbid, Jordan.
[Khalifeh, Mohammad] Jordan University of Science and Technology, Department of Veterinary Basic SciencesIrbid, Jordan.
[Al-Azaizeh, Rasha] Jordan University of Science and Technology, Department of Veterinary Basic SciencesIrbid, Jordan.
[Masaadeh, Amr] Jordan University of Science and Technology, Faculty of Medicine, Department of Pathology and MicrobiologyIrbid, Jordan.
[Al-Rusan, M. Omar] Jordan University of Science and Technology, Faculty of Medicine, Department of Pathology and MicrobiologyIrbid, Jordan.
[Haddad, K. Husam] Ministry of Health, Department of Pathology and Laboratory MedicineAmman, Jordan.
RP AlQudah, M (reprint author), Jordan University of Science and Technology, Faculty of Medicine, Department of Pathology and Microbiology, Irbid, Jordan.
EM m.alqudah12@just.edu.jo
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610752
EP 1610762
DI 10.3389/pore.2022.1610752
PG 11
ER
PT J
AU Shen, X
Mo, X
Tan, W
Mo, X
Li, L
Yu, F
He, J
Deng, Z
Xing, Sh
Chen, Z
Yang, J
AF Shen, Xiaoju
Mo, Xiaocheng
Tan, Weidan
Mo, Xiaoxiang
Li, Li
Yu, Fei
He, Jingchuan
Deng, Zhihua
Xing, Shangping
Chen, Zhiquan
Yang, Jie
TI KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; lung adenocarcinoma; immune infiltration; KIAA1199
ID biomarker; prognosis; lung adenocarcinoma; immune infiltration; KIAA1199
AB Background: KIAA1199 has been considered a key regulator of carcinogenesis. However, the relationship between KIAA1199 and immune infiltrates, as well as its prognostic value in lung adenocarcinoma (LUAD) remains unclear. Methods: The expression of KIAA1199 and its influence on tumor prognosis were analyzed using a series of databases, comprising TIMER, GEPIA, UALCAN, LCE, Prognoscan and Kaplan-Meier Plotter. Further, immunohistochemistry (IHC), western blot (WB) and receiver operating characteristic (ROC) curve analyses were performed to verify our findings. The cBioPortal was used to investigate the genomic alterations of KIAA1199. Prediction of candidate microRNA (miRNAs) and transcription factor (TF) targeting KIAA1199, as well as GO and KEGG analyses, were performed based on LinkedOmics. TIMER and TISIDB databases were used to explore the relationship between KIAA1199 and tumor immune infiltration. Results: High expression of KIAA1199 was identified in LUAD and Lung squamous cell carcinoma (LUSC) patients. High expression of KIAA1199 indicated a worse prognosis in LUAD patients. The results of IHC and WB analyses showed that the expression level of KIAA1199 in tumor tissues was higher than that in adjacent tissues. GO and KEGG analyses indicated KIAA1199 was mainly involved in extracellular matrix (ECM)-receptor interaction and extracellular matrix structure constituent. KIAA1199 was positively correlated with infiltrating levels of CD4+ T cells, macrophages, neutrophil cells, dendritic cells, and showed positive relationship with immune marker subsets expression of a variety of immunosuppressive cells. Conclusion: High expression of KIAA1199 predicts a poor prognosis of LUAD patients. KIAA1199 might exert its carcinogenic role in the tumor microenvironment via participating in the extracellular matrix formation and regulating the infiltration of immune cells in LUAD. The results indicate that KIAA1199 might be a novel biomarker for evaluating prognosis and immune cell infiltration in LUAD.
C1 [Shen, Xiaoju] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Mo, Xiaocheng] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Tan, Weidan] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Mo, Xiaoxiang] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Li, Li] Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Department of PharmacologyNanning, China.
[Yu, Fei] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[He, Jingchuan] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Deng, Zhihua] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Xing, Shangping] Guangxi Medical University, School of Pharmacy, Guangxi Key Laboratory of Bioactive Molecules Research and EvaluationNanning, China.
[Chen, Zhiquan] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
[Yang, Jie] Guangxi Medical University, School of Pharmacy, Department of PharmacologyNanning, China.
RP Yang, J (reprint author), Guangxi Medical University, School of Pharmacy, Department of Pharmacology, Nanning, China.
EM jieyang2016@gxmu.edu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2022
VL 28
IS 4
BP 1610754
EP 1610769
DI 10.3389/pore.2022.1610754
PG 16
ER
PT J
AU Olah, O
Majlat, E
Koszo, R
Vereb, Z
Voros, A
AF Olah, Orsolya
Majlat, Edit
Koszo, Renata
Vereb, Zoltan
Voros, Andras
TI Predictive role of neostromal CD10 expression in breast cancer patients treated with neoadjuvant chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE advanced breast cancer; predictive factors; CD10; neoadjuvant therapy; neostroma
ID advanced breast cancer; predictive factors; CD10; neoadjuvant therapy; neostroma
AB Background: The therapeutic strategy of invasive breast cancer is based on routine histopathological markers (estrogen-, progesterone receptor, HER2, Ki67) routinely evaluated in tumor cells. However, the assessment of cancer stroma could influence therapeutic strategies. Studies have shown that stromal expression of CD10, a zinc-dependent metalloproteinase, is associated with biological aggressiveness of the tumor. In the present retrospective study, we aimed to evaluate stromal CD10 expression and association between CD10 expression and response to neoadjuvant chemotherapy in invasive breast cancer. Methods: CD10 immunohistochemistry was performed on core biopsies taken before the neoadjuvant therapy. Stromal CD10 expression was determined and compared with well-known predictive and prognostic tissue markers as well as with the following groups defined according to the degree of tumor response: no regression, partial regression, and complete regression. Results: A total of 60 locally advanced invasive breast carcinomas of “no special type” were included. The proportion of CD10 positive tumors was significantly higher in the “no regression” group compared to “complete regression” group (p = 0.000). Stromal CD10 expression was found to be significantly associated with decrease in response to neoadjuvant chemotherapy. According to CD10 expression we did not find any difference in hormone receptor status, Ki67, tumor grade or neostromal area. Conclusion: Our data suggest that CD10 expression can serve as a predictive marker of the effect of neoadjuvant chemotherapy in breast cancer patients. Therefore, its inclusion into the routine assessment of biopsies to tailor tumorspecific therapeutic strategies merits consideration.
C1 [Olah, Orsolya] University of Szeged, Department of PathologySzeged, Hungary.
[Majlat, Edit] University of Szeged, Department of PathologySzeged, Hungary.
[Koszo, Renata] University of Szeged, Department of OncotherapySzeged, Hungary.
[Vereb, Zoltan] University of Szeged, Department of Dermatology and AllergologySzeged, Hungary.
[Voros, Andras] University of Szeged, Department of PathologySzeged, Hungary.
RP Voros, A (reprint author), University of Szeged, Department of Pathology, Szeged, Hungary.
EM andrasvoros@libero.it
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610598
EP 1610605
DI 10.3389/pore.2022.1610598
PG 8
ER
PT J
AU Behnke, A
Cayre, A
De Maglio, G
Giannini, G
Habran, L
Tarsitano, M
Chetta, M
Cappellen, D
Lespagnol, A
Le Naoures, C
Massazza, G
Destro, A
Bonzheim, I
Rau, A
Battmann, A
Kah, B
Watkin, E
Hummel, M
AF Behnke, Anke
Cayre, Anne
De Maglio, Giovanna
Giannini, Giuseppe
Habran, Lionel
Tarsitano, Marina
Chetta, Massimiliano
Cappellen, David
Lespagnol, Alexandra
Le Naoures, Cecile
Massazza, Gabriella
Destro, Annarita
Bonzheim, Irina
Rau, Achim
Battmann, Achim
Kah, Bettina
Watkin, Emmanuel
Hummel, Michael
TI FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE non-small cell lung cancer; epidermal growth factor receptor; DNA mutational analysis; clinical decision-making; turnaround time
ID non-small cell lung cancer; epidermal growth factor receptor; DNA mutational analysis; clinical decision-making; turnaround time
AB Accurate testing for epidermal growth factor receptor (EGFR) variants is essential for informing treatment decisions in non-small cell lung cancer (NSCLC). Automated diagnostic workflows may allow more streamlined initiation of targeted treatments, where appropriate, while comprehensive variant analysis is ongoing. FACILITATE, a real-world, prospective, multicenter, European study, evaluated performance and analytical turnaround time of the Idylla™ EGFR Mutation Test compared with local reference methods. Sixteen sites obtained formalin-fixed paraffin-embedded biopsy samples with ≥ 10% neoplastic cells from patients with NSCLC. Consecutive 5 μm sections from patient samples were tested for clinically relevant NSCLC-associated EGFR variants using the Idylla™ EGFR Mutation Test and local reference methods; performance (concordance) and analytical turnaround time were compared. Between January 2019 and November 2020, 1,474 parallel analyses were conducted. Overall percentage agreement was 97.7% [n = 1,418; 95% confidence interval (CI): 96.8–98.3], positive agreement, 87.4% (n = 182; 95% CI: 81.8–91.4) and negative agreement, 99.2% (n = 1,236; 95% CI: 98.5–99.6). There were 38 (2.6%) discordant cases. Ninety percent of results were returned with an analytical turnaround time of within 1 week using the Idylla™ EGFR Mutation Test versus ~22 days using reference methods. The Idylla™ EGFR Mutation Test performed well versus local methods and had shorter analytical turnaround time. The Idylla™ EGFR Mutation Test can thus support application of personalized medicine in NSCLC.
C1 [Behnke, Anke] Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Institute of Pathology and Berlin Institute of HealthBerlin, Germany.
[Cayre, Anne] Centre Jean-Perrin, Departement de PathologieClermont-Ferrand, France.
[De Maglio, Giovanna] Azienda Sanitaria Universitaria Friuli Centrale, Santa Maria della Misericordia Hospital, Pathology DepartmentUdine, Italy.
[Giannini, Giuseppe] Universita di Roma La Sapienza, Department Molecular MedicineRome, Italy.
[Habran, Lionel] CHU Sart Tilman, Department of AnatomopathologyLiege, Belgium.
[Tarsitano, Marina] U.O.C. di Genetica Medica, Medical Genetics Laboratory, and Ospedale Antonio Cardarelli, Di Laboratorio, A.O.R.N. CardarelliNaples, Italy.
[Chetta, Massimiliano] U.O.C. di Genetica Medica, Medical Genetics Laboratory, and Ospedale Antonio Cardarelli, Di Laboratorio, A.O.R.N. CardarelliNaples, Italy.
[Cappellen, David] Centre Hospitalier Universitaire de Bordeaux, Hopital du Haut Leveque, Service de Biologie des TumeursPessac, France.
[Lespagnol, Alexandra] CHU de Rennes, Laboratoire de Genetique Somatique des CancersRennes, France.
[Le Naoures, Cecile] CHU de Rennes, Service d’Anatomie et Cytologie PathologiquesRennes, France.
[Massazza, Gabriella] ASST Papa Giovanni XXIII, Dipartimento Medicina di Laboratorio Anatomia PatologicaBergamo, BG, Italy.
[Destro, Annarita] Humanitas Clinical and Research Center—IRCCS, Pathology DepartmentMilan, Italy.
[Bonzheim, Irina] University Hospital Tubingen, Eberhard Karls University of Tubingen and Comprehensive Cancer Center, Institute of Pathology and NeuropathologyTubingen, Germany.
[Rau, Achim] University Hospital Tubingen, Eberhard Karls University of Tubingen and Comprehensive Cancer Center, Institute of Pathology and NeuropathologyTubingen, Germany.
[Battmann, Achim] Institut fur Pathologie und Zytodiagnostik am Krankenhaus NordwestFrankfurt, Germany.
[Kah, Bettina] Institute for Hematopathology HamburgHamburg, Germany.
[Watkin, Emmanuel] CYPATHVilleurbanne, France.
[Hummel, Michael] Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Institute of Pathology and Berlin Institute of HealthBerlin, Germany.
RP Hummel, M (reprint author), Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Institute of Pathology and Berlin Institute of Health, Berlin, Germany.
EM michael.hummel@charite.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610707
EP 1610721
DI 10.3389/pore.2023.1610707
PG 15
ER
PT J
AU Wang, Ch
Wang, W
Xu, R
Xiang, J
AF Wang, Changrong
Wang, Wei
Xu, Rujun
Xiang, Jingjing
TI Case report: Large-size intramuscular nodular fasciitis, a challenging histopathologic diagnosis confirmed by molecular detection of USP6 gene rearrangement: Case report and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE nodular fasciitis; gene rearrangement; large-size; intramuscular; USP6
ID nodular fasciitis; gene rearrangement; large-size; intramuscular; USP6
AB The intramuscular subtype of nodular fasciitis (NF) is rare with lesions normally not more than 2 cmin size and characterized by pseudosarcomatousmorphology.We report a case of a 27-year-old man with a large-size intramuscular NF. The patient came for treatment complaining of an increasingly enlarged mass in the left upper arm for 4months. Magnetic resonance imaging (MRI) confirmed the presence of a well-defined tumor measuring 5 cm within the outer edge of themiddle humerus. Microscopically, the neoplasm was rich in fibroblasts and myofibroblasts in an interlaced pattern with high mitotic index and evident multinuclear giant cells. Erythrocyte extravasation was easily seen in the stroma. The tumor border was infiltrative. Immunohistochemically, the tumor cells were positive for smooth muscle actin (SMA) and negative for cytokeratin, desmin, H-Caldesmon, CD34, S100, ALK, and β-catenin. Fibrosarcoma was highly suspected by histopathological and immunohistochemical examination. Molecular detection demonstrated evidence of ubiquitin-specific peptidase 6 (USP6) gene rearrangement in this tumor. Based on the findings, the tumor was diagnosed as intramuscular NF. At 56 months after the initial surgery, the patient had recovered with no evidence of recurrence or metastasis. Large-size intramuscular NF is very rare and easily overdiagnosed as malignant tumor due to its obvious pseudosarcomatoid pathological features. USP6 gene rearrangement detection can effectively avoid this major misdiagnosis.
C1 [Wang, Changrong] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, Zhejiang, China.
[Wang, Wei] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, Zhejiang, China.
[Xu, Rujun] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, Zhejiang, China.
[Xiang, Jingjing] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, Zhejiang, China.
RP Xiang, J (reprint author), Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical Pathology, Hangzhou, China.
EM xiang_cell@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610785
EP 1610791
DI 10.3389/pore.2023.1610785
PG 7
ER
PT J
AU Zhang, Sh
Xu, H
Li, W
Ji, J
Jin, Q
Chen, L
Gan, Q
Tao, Q
Chai, Y
AF Zhang, Shouhua
Xu, Hongyan
Li, Weiming
Ji, Jianfeng
Jin, Qifang
Chen, Leifeng
Gan, Qiang
Tao, Qiang
Chai, Yong
TI MDM2 promotes cancer cell survival through regulating the expression of HIF-1α and pVHL in retinoblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIF-1α; retinoblastoma; MDM2; pVHL; hypoxia
ID HIF-1α; retinoblastoma; MDM2; pVHL; hypoxia
AB Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study,we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL,while cells withMDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment.
C1 [Zhang, Shouhua] Jiangxi Provincial Children’s Hospital, Department of General SurgeryNanchang, Jiangxi, China.
[Xu, Hongyan] Jiangxi Provincial Children’s Hospital, Department of General SurgeryNanchang, Jiangxi, China.
[Li, Weiming] Jiangxi Provincial Children’s Hospital, Department of General SurgeryNanchang, Jiangxi, China.
[Ji, Jianfeng] Joint Support Forces of the Chinese People’s Liberation Army 908 Hospital, Department of UltrasoundNanchang, Jiangxi, China.
[Jin, Qifang] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, Jiangxi, China.
[Chen, Leifeng] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, Jiangxi, China.
[Gan, Qiang] Jiangxi Provincial Children’s Hospital, Department of OphthalmologyNanchang, Jiangxi, China.
[Tao, Qiang] Jiangxi Provincial Children’s Hospital, Department of General SurgeryNanchang, Jiangxi, China.
[Chai, Yong] Jiangxi Provincial Children’s Hospital, Department of OphthalmologyNanchang, Jiangxi, China.
RP Chai, Y (reprint author), Jiangxi Provincial Children’s Hospital, Department of Ophthalmology, Nanchang, China.
EM yc3408954524@hotmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610801
EP 1610811
DI 10.3389/pore.2023.1610801
PG 11
ER
PT J
AU Liao, X
Chen, J
Luo, D
Luo, B
Huang, W
Xie, W
AF Liao, XiaoLi
Chen, Junming
Luo, Dongcheng
Luo, Baohua
Huang, Wenfeng
Xie, Weimin
TI Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; hepatocellular carcinoma; mutation; DNA methylation; metastasis associated lung adenocarcinoma transcript 1 (MALAT1); interacting proteins; competing endogenous RNAs (ceRNAs); multi-omics
ID prognosis; hepatocellular carcinoma; mutation; DNA methylation; metastasis associated lung adenocarcinoma transcript 1 (MALAT1); interacting proteins; competing endogenous RNAs (ceRNAs); multi-omics
AB Background: This study aimed to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC). Methods: We constructed a MALAT1 protein-protein interaction network using the STRING database and a network of competing endogenous RNAs (ceRNAs) using the StarBase database. Using data from the GEPIA2 database, we studied the association between genes in these networks and survival of patients with HCC. The potential mechanisms underlying the relationship between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test. Results: Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with mutations in two genes leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression, including the cell cycle, DNA damage repair, mismatch repair, homologous recombination, molecular cancer m6A, exosome, ferroptosis, infiltration of lymphocyte (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for patients with low expression, while the corresponding median OS was 40.5 and 78.3 months. In subgroup analysis of patients with vascular invasion, cirrhosis, and HBsAg positive or AFP positive, MALAT1 overexpression was significantly associated with shorter PFS and OS. Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661–0.731. Additionally, MALAT1 expression level was significantly associated with liver cirrhosis, vascular invasion, and tumor capsular infiltration (p < 0.05 for all). Conclusion: MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.
C1 [Liao, XiaoLi] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Chen, Junming] Fujian Medical University Union Hospital, Department of Medical OncologyFuzhou, China.
[Luo, Dongcheng] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
[Luo, Baohua] Jiangbin Hospital, Department of GastroenterologyNanning, China.
[Huang, Wenfeng] Second Affiliated Hospital of Guangxi Medical University, Department of Medical OncologyNanning, China.
[Xie, Weimin] Guangxi Medical University Cancer Hospital, Department of First ChemotherapyNanning, China.
RP Xie, W (reprint author), Guangxi Medical University Cancer Hospital, Department of First Chemotherapy, Nanning, China.
EM xieweimin@gxmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610808
EP 1610833
DI 10.3389/pore.2022.1610808
PG 26
ER
PT J
AU Fan, Z
Liu, B
Shang, P
AF Fan, Zizheng
Liu, Bing
Shang, Peizhong
TI Development and validation of a nomogram prediction model based on albumin-to-alkaline phosphatase ratio for predicting the prognosis of gallbladder carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; nomogram; gallbladder carcinoma; independent risk factors; AAPR
ID prognosis; nomogram; gallbladder carcinoma; independent risk factors; AAPR
AB Gallbladder carcinoma (GBC) is a rare biliary tract cancer with a high recurrence rate and a poor prognosis. Albumin-alkaline phosphatase ratio (AAPR) has been demonstrated to be a prognostic predictor for several cancers, but its predictive value for GBC patients remains unknown. The aim of this study was to investigate the predictive role of AAPR in GBC patients and to develop a novel nomogram prediction model for GBC patients. We retrospectively collected data from 80 patients who underwent surgery at the Hospital of 81st Group Army PLA as a training cohort. Data were collected from 70 patients with the same diagnosis who underwent surgery at the First Affiliated Hospital of Hebei North University as an external verification cohort. The optimal cut-off value of AAPR was determined using X-tile software. A nomogram for the overall survival (OS) based on multivariate Cox regression analysis was developed and validated using calibration curves, Harrell’s concordance index, the receiver operating characteristic curves, and decisive curve analyses. The optimal cut-off value of AAPR was .20. Univariate and multivariate Cox regression analyses demonstrated that BMI (p = .043), R0 resection (p = .001), TNM stage (p = .005), and AAPR (p = .017) were independent risk factors for GBC patients. In terms of consistency, discrimination, and net benefit, the nomogram incorporating these four independent risk factors performed admirably. AAPR is an independent predictor of GBC patients undergoing surgery, and a novel nomogram prediction model based on AAPR showed superior predictive ability.
C1 [Fan, Zizheng] Hebei North University, Department of Graduate SchoolZhangjiakou, China.
[Liu, Bing] The Hospital of 81st Group Army PLA, Department of Hepatobiliary SurgeryZhangjiakou, China.
[Shang, Peizhong] The Hospital of 81st Group Army PLA, Department of Hepatobiliary SurgeryZhangjiakou, China.
RP Shang, P (reprint author), The Hospital of 81st Group Army PLA, Department of Hepatobiliary Surgery, Zhangjiakou, China.
EM spz251@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610818
EP 1610830
DI 10.3389/pore.2022.1610818
PG 13
ER
PT J
AU Hou, J
Guo, P
Lu, Y
Jin, X
Liang, K
Zhao, N
Xue, Sh
Zhou, Ch
Wang, G
Zhu, X
Hong, H
Chen, Y
Lu, H
Wang, W
Xu, Ch
Han, Y
Cai, Sh
Liu, Y
AF Hou, Jun
Guo, Peng
Lu, Yujiao
Jin, Xiaokang
Liang, Ke
Zhao, Na
Xue, Shunxu
Zhou, Chengmin
Wang, Guoqiang
Zhu, Xin
Hong, Huangming
Chen, Yungchang
Lu, Huafei
Wang, Wenxian
Xu, Chunwei
Han, Yusheng
Cai, Shangli
Liu, Yang
TI A prognostic 15-gene model based on differentially expressed genes among metabolic subtypes in diffuse large B-cell lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; risk score; drug sensitivity; DEGs; diffuse large B-cell lymphoma (DLBCL); metabolic subtypes
ID prognosis; risk score; drug sensitivity; DEGs; diffuse large B-cell lymphoma (DLBCL); metabolic subtypes
AB The outcomes of patients with diffuse large B-cell lymphoma (DLBCL) vary widely, and about 40% of them could not be cured by the standard first-line treatment, R-CHOP, which could be due to the high heterogeneity of DLBCL. Here, we aim to construct a prognostic model based on the genetic signature of metabolic heterogeneity of DLBCL to explore therapeutic strategies for DLBCL patients. Clinical and transcriptomic data of one training and four validation cohorts of DLBCL were obtained from the GEO database. Metabolic subtypes were identified by PAM clustering of 1,916 metabolic genes in the 7 major metabolic pathways in the training cohort. DEGs among the metabolic clusters were then analyzed. In total, 108 prognosis-related DEGs were identified. Through univariable Cox and LASSO regression analyses, 15 DEGs were used to construct a risk score model. The overall survival (OS) and progression-free survival (PFS) of patients with high risk were significantly worse than those with low risk (OS: HR 2.86, 95%CI 2.04–4.01, p < 0.001; PFS: HR 2.42, 95% CI 1.77–3.31, p < 0.001). This model was also associated with OS in the four independent validation datasets (GSE10846: HR 1.65, p = 0.002; GSE53786: HR 2.05, p = 0.02; GSE87371: HR 1.85, p = 0.027; GSE23051: HR 6.16, p = 0.007) and PFS in the two validation datasets (GSE87371: HR 1.67, p = 0.033; GSE23051: HR 2.74, p = 0.049). Multivariable Cox analysis showed that in all datasets, the risk model could predict OS independent of clinical prognosis factors (p < 0.05). Compared with the high-risk group, patients in the low-risk group predictively respond to R-CHOP (p = 0.0042), PI3K inhibitor (p < 0.05), and proteasome inhibitor (p < 0.05). Therefore, in this study, we developed a signature model of 15 DEGs among 3 metabolic subtypes, which could predict survival and drug sensitivity in DLBCL patients.
C1 [Hou, Jun] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Guo, Peng] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Lu, Yujiao] Burning Rock BiotechGuangzhou, China.
[Jin, Xiaokang] Burning Rock BiotechGuangzhou, China.
[Liang, Ke] Burning Rock BiotechGuangzhou, China.
[Zhao, Na] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Xue, Shunxu] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Zhou, Chengmin] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Wang, Guoqiang] Burning Rock BiotechGuangzhou, China.
[Zhu, Xin] Burning Rock BiotechGuangzhou, China.
[Hong, Huangming] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Medical OncologyChengdu, China.
[Chen, Yungchang] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Medical OncologyChengdu, China.
[Lu, Huafei] Burning Rock BiotechGuangzhou, China.
[Wang, Wenxian] The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Department of Clinical TrialHangzhou, China.
[Xu, Chunwei] Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of SciencesHangzhou, China.
[Han, Yusheng] Burning Rock BiotechGuangzhou, China.
[Cai, Shangli] Burning Rock BiotechGuangzhou, China.
[Liu, Yang] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
RP Liu, Y (reprint author), University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of Pathology, Chengdu, China.
EM liuyang@scszlyy.org.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610819
EP 1610831
DI 10.3389/pore.2023.1610819
PG 13
ER
PT J
AU Deng, M
Luo, R
Huang, J
Luo, Y
Song, Q
Liang, H
Xu, Ch
Yuan, W
Hou, Y
AF Deng, Minying
Luo, Rongkui
Huang, Jie
Luo, Yuanlong
Song, Qi
Liang, Huaiyu
Xu, Chen
Yuan, Wei
Hou, Yingyong
TI Clinicopathologic features of gastric glomus tumor: A report of 15 cases and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE glomus tumor; gastric tumor; immunohistochemistry; molecular genetics; prognosis
ID glomus tumor; gastric tumor; immunohistochemistry; molecular genetics; prognosis
AB Objective: Glomus tumor is a relatively uncommon soft tissue neoplasm predominantly occurring in upper extremity (fingers), less reported in stomach. This study aimed to discuss the clinicopathologic features of gastric glomus tumor (GGT) and then provide reference for clinical practice. Methods: A retrospective analysis of all cases pathologically diagnosed of GGT was performed, pathological findings were correlated with clinical information, immunohistochemical studies, next-generation sequencing, and patient follow-ups. A review of literature by searching similar cases was conducted to summarize previous knowledge of GGTs. Results: Our study identified 15GGTsincluded 5 males and 10 females, aged between 35–75 years old (median, 49 years old). The tumor was located to the gastric corpus in 6 cases (40%) and to the antrum in 9 cases (60%). The maximum tumor diameter ranged between 1–4 cm(median, 1.5 cm). There were 11 cases (73%) of solid glomus tumor, 3 cases (20%) ofmixture of solid glomus tumor and glomangioma, and 1 case (7%) of glomangiomyoma. Partial spindle cell area was observed in 3 cases (20%), moderate cellular atypia in 1 case (7%), atypicalmitosis in 1 case (7%), vascular invasion in 5 cases (33%), neural invasion in 6 cases (40%) and tumor necrosis in 1 case (7%). Tumor cells expressed Collagen type IV, α-smooth muscle actin (α-SMA), and synaptophysin in most cases. The Ki67 index varied from 1% to 30%. Nextgeneration sequencing reported EGFR, PIK3CA, KEAP1 and TP53 mutation. The outcome information was obtained in 12 (80%) cases, followed for 6–63 months, 11 patients (92%) had tumor-free survival and 1 patient (8%) developed liver metastasis 26 months after surgery. Literature review obtained 16 previously reported malignant GGT cases. In terms of the total 31 cases, univariate analysis revealed that the atypical mitosis (OS: p=0.009; DFS: p = 0.010) and severe cellular atypia (OS: p = 0.007; DFS: p = 0.004) were significantly associated with poor prognosis (patient death). Conclusion: GGT is indolent, while long-term close follow-up should be required in the presence of increasing number of risk factors. Malignant GGT is relatively uncommon and predisposes to liver metastasis, calling for accumulation of large-sample data and experience.
C1 [Deng, Minying] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Luo, Rongkui] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Huang, Jie] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Luo, Yuanlong] Shanghai University of Traditional Chinese MedicineShanghai, China.
[Song, Qi] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Liang, Huaiyu] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Xu, Chen] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Yuan, Wei] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Hou, Yingyong] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
RP Hou, Y (reprint author), Fudan University, Zhongshan Hospital, Department of Pathology, Shanghai, China.
EM hou.yingyong@zs-hospital.sh.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610824
EP 1610838
DI 10.3389/pore.2022.1610824
PG 15
ER
PT J
AU Fejes, Zs
Santa, F
Jenei, A
Kiraly, EI
Varga, L
Kuthi, L
AF Fejes, Zsuzsanna
Santa, Fanni
Jenei, Alex
Kiraly, Elod Istvan
Varga, Linda
Kuthi, Levente
TI Angiomyolipoma of the kidney— Clinicopathological analysis of 52 cases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE AML; angiomyolipoma; kidney tumor; tuberous sclerosis; nephrectomy
ID AML; angiomyolipoma; kidney tumor; tuberous sclerosis; nephrectomy
AB The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type,whileMelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50swith an average sizeof 50–60mmat the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings.
C1 [Fejes, Zsuzsanna] University of Szeged, Department of RadiologySzeged, Hungary.
[Santa, Fanni] University of Szeged, Department of PathologySzeged, Hungary.
[Jenei, Alex] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kiraly, Elod Istvan] University of Szeged, Department of UrologySzeged, Hungary.
[Varga, Linda] University of Szeged, Department of OncotherapySzeged, Hungary.
[Kuthi, Levente] University of Szeged, Department of PathologySzeged, Hungary.
RP Kuthi, L (reprint author), University of Szeged, Department of Pathology, Szeged, Hungary.
EM kuthi.levente@med.u-szeged.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610831
EP 1610841
DI 10.3389/pore.2022.1610831
PG 11
ER
PT J
AU Phikulsod, P
Sukpanichnant, S
Kunacheewa, Ch
Chieochansin, Th
Junking, M
Yenchitsomanus, Pth
AF Phikulsod, Ployploen
Sukpanichnant, Sanya
Kunacheewa, Chutima
Chieochansin, Thaweesak
Junking, Mutita
Yenchitsomanus, Pa-thai
TI High prevalence of Wilms tumor 1 expression in multiple myeloma and plasmacytoma: A cohort of 142 Asian patients’ samples
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; immunohistochemistry (IHC); plasmacytoma; WT1 protein; cohort study Thailand; Asian cohort; treatment outcome; clinical relevance
ID multiple myeloma; immunohistochemistry (IHC); plasmacytoma; WT1 protein; cohort study Thailand; Asian cohort; treatment outcome; clinical relevance
AB Wilms tumor 1 (WT1) is a promising target antigen for cancer immunotherapy. However, WT1 protein expression and its clinical correlation in multiple myeloma (MM) patients are still limited. We, therefore, investigated WT1 expression in 142 bone marrow and plasmacytoma samples of MM patients at different stages of the disease by immunohistochemistry. The correlations between WT1 expression and clinical parameters or treatment outcomes were evaluated. The overall positive rate of WT1 expression was 91.5%; this high prevalence was found in both bone marrow and plasmacytoma samples, regardless of the disease status. Cytoplasmic WT1 expression was correlated with high serum free light chain ratio at presentation. However, no significant association between WT1 expression and treatment outcome was observed. This study confirms the high prevalence of WT1 expression in an Asian cohort of MM, encouraging the development of immunotherapy targeting WT1 in MM patients, particularly in those with extramedullary plasmacytoma or relapsed disease.
C1 [Phikulsod, Ployploen] Mahidol University, Faculty of Medicine Siriraj Hospital, Research Department, Division of Molecular MedicineBangkok, Thailand.
[Sukpanichnant, Sanya] Mahidol University, Faculty of Medicine Siriraj Hospital, Department of PathologyBangkok, Thailand.
[Kunacheewa, Chutima] Mahidol University, Faculty of Medicine Siriraj Hospital, Department of MedicineBangkok, Thailand.
[Chieochansin, Thaweesak] Mahidol University, Faculty of Medicine Siriraj Hospital, Research Department, Division of Molecular MedicineBangkok, Thailand.
[Junking, Mutita] Mahidol University, Faculty of Medicine Siriraj Hospital, Research Department, Division of Molecular MedicineBangkok, Thailand.
[Yenchitsomanus, Pa-thai] Mahidol University, Faculty of Medicine Siriraj Hospital, Research Department, Division of Molecular MedicineBangkok, Thailand.
RP Yenchitsomanus, Pth (reprint author), Mahidol University, Faculty of Medicine Siriraj Hospital, Research Department, Division of Molecular Medicine, Bangkok, Thailand.
EM ptyench@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610844
EP 1610851
DI 10.3389/pore.2023.1610844
PG 8
ER
PT J
AU Chen, T
Peng, Y
Lei, T
Wu, Ch
Wang, H
Shi, Y
AF Chen, Tongbing
Peng, Yan
Lei, Ting
Wu, Chao
Wang, Hui
Shi, Yongqiang
TI Low-grade oncocytic tumour (LOT) of the kidney is characterised by GATA3 positivity, FOXI1 negativity and mTOR pathway mutations
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; clinicopathological characteristics; mTOR; differential diagnosis; low-grade oncocytic tumour (LOT) of the kidney
ID immunohistochemistry; clinicopathological characteristics; mTOR; differential diagnosis; low-grade oncocytic tumour (LOT) of the kidney
AB Aims: We present a 5-case series of low-grade oncocytic tumour of the kidney to further discuss their clinicopathological characteristics. Methods and results: Five patients were included in this study. There were three females and two males aged 45–66 years, with a median age of 65 years. Four tumours were located in the right kidney, and one was located in the left kidney. Most of the tumour sections were yellow-brown in colour. Tumour sizes ranged from 2.5 to 4.5 cm, with a median size of 3 cm. Microscopically, the tumours were well-circumscribed but lacked a fibrous capsule; the tumours consisted of monomorphous oncocytic cells arranged mainly in solid and nested architectural patterns. The tumour cells had uniformly round to oval nuclei and often had perinuclear halos but lacked significant irregularities. Immunohistochemically, the tumour cells showed a diffuse and strong positivity forCK7 andwere negative for CD117. The tumour cellswere also positive for GATA3, E-cadherin, Pax-8, Succinate dehydrogenase B (SDHB) and Fumarate hydratase (FH), and negative for vimentin, Carbonic anhydrase 9 (CA9), CD10, P504s, CK20, TFE3, TFEB, HMB45, ALK and Forkhead box protein I1 (FOXI1). Next-generation sequencing identified genetic variations in these tumours, including MTOR gene mutations (4/5) and PIK3CA gene mutation (1/5). All patients were alive without disease progression at a median follow-up of 32 months (range 10–57months). Conclusion: LOT is an emerging renal entity of indolent behaviour that has morphologic overlap with some renal tumours with eosinophilic cytoplasm, primarily with oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma. Familiarity with the distinctive morphological features, immunophenotype and molecular genetics of LOT helps avoid misdiagnosis.
C1 [Chen, Tongbing] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
[Peng, Yan] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
[Lei, Ting] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
[Wu, Chao] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
[Wang, Hui] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
[Shi, Yongqiang] The Third Affiliated Hospital of Soochow University, Department of PathologyChangzhou, China.
RP Peng, Y (reprint author), The Third Affiliated Hospital of Soochow University, Department of Pathology, Changzhou, China.
EM pengyan871005@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610852
EP 1610858
DI 10.3389/pore.2023.1610852
PG 7
ER
PT J
AU Wang, Z
Wang, J
Zhang, W
Wang, D
Wang, X
Liang, X
AF Wang, Zhuo
Wang, Jinsui
Zhang, Wenwen
Wang, Daoying
Wang, Xiaojun
Liang, Xiaoqin
TI Case report: Urothelial carcinoma of the renal pelvis with trophoblastic differentiation: A rare case report and review of literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE urothelial carcinoma; renal pelvis; trophoblastic differentiation; beta-human chorionic gonadotropin; syncytiotrophoblastic cells
ID urothelial carcinoma; renal pelvis; trophoblastic differentiation; beta-human chorionic gonadotropin; syncytiotrophoblastic cells
AB We report a rare case of urothelial carcinoma (UC) of the renal pelvis with trophoblastic differentiation that occurred in a 55-year-old male patient. The patient presented with gross hematuria and paroxysmal lumbago pain 5 months ago. The enhanced computed tomography (CT) scan demonstrated a large space occupying lesion in the left kidney and multiple retroperitoneal lymph node enlargements. Histologically, high-grade infiltrating urothelial carcinoma (HGUC) contained giant cells which were positive for beta-human chorionic gonadotropin (β-hCG). Three weeks after resection, positron emission tomography and computed tomography (PET-CT) scan showed multiple nodules of metastasis in the left renal region, extensive systemic muscle, bone, lymph node, liver and bilateral lung metastases. The patient underwent bladder perfusion chemotherapy and gemcitabine combined with cisplatin chemotherapy regimens. This is the eighth documented case of UC of the renal pelvis with trophoblastic differentiation. Due to its rarity and extremely poor prognosis, it is important to clarify the characteristics of the disease and make an accurate and prompt diagnosis.
C1 [Wang, Zhuo] Gansu Province People’s Hospital, Department of PathologyLanzhou, Gansu, China.
[Wang, Jinsui] Gansu Province People’s Hospital, Department of PathologyLanzhou, Gansu, China.
[Zhang, Wenwen] Gansu Province People’s Hospital, Department of RadiologyLanzhou, Gansu, China.
[Wang, Daoying] Gansu Province People’s Hospital, Department of the Centre of Positron Emission Tomography-Computed TomographyLanzhou, Gansu, China.
[Wang, Xiaojun] Gansu Province People’s Hospital, Department of Respiratory MedicineLanzhou, Gansu, China.
[Liang, Xiaoqin] Gansu Province People’s Hospital, Department of PathologyLanzhou, Gansu, China.
RP Liang, X (reprint author), Gansu Province People’s Hospital, Department of Pathology, Lanzhou, China.
EM liangxq905@163.com
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Dino G, David G, Parker E, Shepherd RR, Hearn SA, Walton JC. Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder. Cancer, 1993, 71(8):1835–41., DOI 10.1002/1097-0142(19930301)71: 5<1835:aid-cncr2820710519>3.0.co;2-5
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610856
EP 1610862
DI 10.3389/pore.2023.1610856
PG 7
ER
PT J
AU Dapkeviciutė-Purlienė, A
Augustinavicius, V
Zucenka, A
AF Dapkeviciutė-Purlienė, Austėja
Augustinavicius, Vytautas
Zucenka, Andrius
TI Case report: Relapsed/refractory extranodal natural killer/T-cell lymphoma nasal type with extensive central nervous system involvement
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; lymphoma; NK-cell; T-cell; central nervous system
ID case report; lymphoma; NK-cell; T-cell; central nervous system
AB Background: Extranodal natural killer/T-cell lymphoma (ENKL) is a rare subtype of mature T and natural killer cell lymphomas associated with Epstein-Barr virus. Case: A 20-year-old presented with severe neurological symptoms and was diagnosed with stage IV ENKL, nasal type, with CNS involvement. Overall, the patient received nine treatment lines, including chemotherapy, craniospinal irradiation, allogeneic stem cell transplant (alloSCT), donor lymphocyte infusions, and novel agents (Nivolumab, Daratumumab, Thalidomide, Lenalidomide, virus-specific T cells) combined with intrathecal chemotherapy. The treatment effect was evaluated in both blood and CSF (cerebrospinal fluid). First-line SMILE chemotherapy resulted in systemic and CNS remission. Later Cytarabine-based chemotherapy and Daratumumab combination helped to reinduce remission before alloSCT. Conclusion: We show that efficacy monitoring should include both blood and CSF analysis. High-dose Cytarabine-based chemotherapy in combination with Daratumumab and intrathecal chemotherapy may be considered as salvage CNS-directed therapies. We add to existing limited data that Daratumumab penetrates the blood-brain barrier.
C1 [Dapkeviciutė-Purlienė, Austėja] Vilnius University, Faculty of Medicine, Institute of Clinical MedicineVilnius, Lithuania.
[Augustinavicius, Vytautas] Vilnius University, Faculty of Medicine, Department of Radiology, Nuclear Medicine and Physics of MedicineVilnius, Lithuania.
[Zucenka, Andrius] Vilnius University, Faculty of Medicine, Institute of Clinical MedicineVilnius, Lithuania.
RP Dapkeviciutė-Purlienė, A (reprint author), Vilnius University, Faculty of Medicine, Institute of Clinical Medicine, Vilnius, Lithuania.
EM austeja.dapkeviciute@santa.lt
CR Yamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type [Internet]. Blood., 2018, 131131(23):2528–40., DOI 10.1182/blood-2017-12-791418
Yamaguchi M, Miyazaki K. Current treatment approaches for NK/T-cell lymphoma. J Clin Exp Hematop 57:98–108., DOI 10.3960/jslrt. 17018
Yang Y, Li Z, Zhiyang C, Liang H. Extranodal natural killer/T-cell lymphoma nasal type with central nervous system involvement mimicked tuberculous meningitis: A case report. Medicine, Baltimore, 98(34):e16747.
Romero-Guadarrama MB, Aguilar-Martinez E. Extranodal nasal NK/T-cell lymphoma with dissemination to the central nervous system: A case report. Acta Cytol, 2010, 54(5):993–7.
Tse E, Kwong YL. Diagnosis and management of extranodal NK/T cell lymphoma nasal type. Expert Rev Hematol 99(9):861–71., DOI 10.1080/17474086. 2016.1206465
Yanagisawa R, Nakazawa Y, Sakashita K, Saito S, Tanaka M, Shiohara M, et al. Intrathecal donor lymphocyte infusion for isolated leukemia relapse in the central nervous system following allogeneic stem cell transplantation: A case report and literature review. Int J Hematol 103:107–11., DOI 10.1007/s12185-015-1902-1
Zhao J, Zu Y, Han L, Zhang Y, Gui R, Yu F, et al. Treatment of Epstein–Barr virus associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation with intrathecal donor lymphocyte infusion. Bone Marrow Transpl, 2019, 54(6):821–7., DOI 10.1038/s41409-018-0409-9
YamaguchiM, Oguchi M, Suzuki R. Extranodal NK/T-cell lymphoma: Updates in biology and management strategies [Internet]. Best Pract Res Clin Haematol, 2018, 3131(3):315–21., DOI 10.1016/j.beha.2018.07.002
Chan TSY, Li J, Loong F, Khong PL, Tse E, Kwong YL. PD1 blockade with lowdose nivolumab in NK/T cell lymphoma failing l-asparaginase: Efficacy and safety [internet]. Ann Hematol 9797(1):193–6., DOI 10.1007/s00277-017-3127-2
Li X, Cheng Y, ZhangM, Yan J, Li L, Fu X, et al. Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J Hematol Oncol, 2018, 11(1):15., DOI 10. 1186/s13045-018-0559-7
Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood., 2017, 129(17):2437–42., DOI 10.1182/ blood-2016-12-756841
AbidH,Watthanasuntorn K, Shah O, Gnanajothy R. Efficacy of pembrolizumab and nivolumab in crossing the blood brain barrier. Cureus, 2019, 11(4):e4446., DOI 10.7759/ cureus.4446
Van Bussel MTJ, Beijnen JH, Brandsma D. Intracranial antitumor responses of nivolumab and ipilimumab: A pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. BMC Cancer, 2019, 19(1):519., DOI 10. 1186/s12885-019-5741-y
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Kim W-S, Eom H-S, Yeh S-P, Cho S-G, Heo DS, Kim JS, et al. Daratumumab monotherapy for patients with relapsed or refractory, R/R, natural killer/T-cell lymphoma, NKTCL), nasal type: An open-label, single-arm, multicenter phase 2 study. Blood, 2018, 132(1):1617., DOI 10.1182/blood-2018-99-111885
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610866
EP 1610872
DI 10.3389/pore.2022.1610866
PG 7
ER
PT J
AU Inukai, K
Kise, K
Hayashi, Y
Jia, W
Muramatsu, F
Okamoto, N
Konishi, H
Akuta, K
Kidoya, H
Takakura, N
AF Inukai, Koichi
Kise, Kazuyoshi
Hayashi, Yumiko
Jia, Weizhen
Muramatsu, Fumitaka
Okamoto, Naoki
Konishi, Hirotaka
Akuta, Keigo
Kidoya, Hiroyasu
Takakura, Nobuyuki
TI Cancer apelin receptor suppresses vascular mimicry in malignant melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epithelial-mesenchymal transition; melanoma; apelin; apelin receptor; neovascularization
ID epithelial-mesenchymal transition; melanoma; apelin; apelin receptor; neovascularization
AB Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin–apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin–APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin–APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial–mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-β/smad signaling pathway in our model. We propose that apelin- APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.
C1 [Inukai, Koichi] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Kise, Kazuyoshi] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Hayashi, Yumiko] University of Fukui, Faculty of Medical Sciences, Department of Integrative Vascular BiologyFukui, Japan.
[Jia, Weizhen] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Muramatsu, Fumitaka] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Okamoto, Naoki] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Konishi, Hirotaka] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Akuta, Keigo] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
[Kidoya, Hiroyasu] University of Fukui, Faculty of Medical Sciences, Department of Integrative Vascular BiologyFukui, Japan.
[Takakura, Nobuyuki] Osaka University, Research Institute for Microbial Diseases, Department of Signal TransductionSuita, Japan.
RP Takakura, N (reprint author), Osaka University, Research Institute for Microbial Diseases, Department of Signal Transduction, Suita, Japan.
EM ntakaku@biken.osaka-u.ac.jp
CR Serene HL, Tian J, Reversade B. Elabela: A hormone essential for heart development signals via the apelin receptor. Dev Cel, 2013, 27(6):672–80., DOI 10.1016/j.devcel.2013.11.002
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610867
EP 1610877
DI 10.3389/pore.2023.1610867
PG 11
ER
PT J
AU Wang, Sh
Zheng, Q
Wang, J
Chen, Sh
Chen, L
AF Wang, Shaoyu
Zheng, Qiaomei
Wang, Jinhua
Chen, Shaozhan
Chen, Lihong
TI Long non-coding RNA MYU promotes ovarian cancer cell proliferation by sponging miR-6827-5p and upregulating HMGA1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lncRNA; ovarian cancer; HMGA1; MYU; miR-6827-5p
ID lncRNA; ovarian cancer; HMGA1; MYU; miR-6827-5p
AB Background: Long non-coding RNAs (lncRNAs) have been confirmed to play vital roles in tumorigenesis. LncRNA MYU has recently been reported as an oncogene in several kinds of tumors. However, MYU’s expression status and potential involvement in ovarian cancer (OC) remain unclear. In this study, we explored the underlying role of MYU in OC. Methods and results: The expression of MYU was upregulated in OC tissues, and MYU’s overexpression was significantly correlated with the FIGO stage and lymphatic metastasis. Knockdown of MYU inhibited cell proliferation in SKOV3 and A2780 cells. Mechanistically, MYU directly interacted with miR- 6827-5p in OC cells; HMGA1 is a downstream target gene of miR-6827- 5p. Furthermore, MYU knockdown increased the expression of miR-6827-5p and decreased the ex pression of HMGA1. Restoration of HMGA1 expression reversed the influence on cell proliferation caused by MYU knockdown. Conclusion: MYU functions as a ceRNA that positively regulates HMGA1 expression by sponging miR-6827-5p in OC cells, which may provide a potential target and biomarker for the diagnosis or prognosis of OC.
C1 [Wang, Shaoyu] Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and GynecologyFuzhou, China.
[Zheng, Qiaomei] Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and GynecologyFuzhou, China.
[Wang, Jinhua] Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and GynecologyFuzhou, China.
[Chen, Shaozhan] Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and GynecologyFuzhou, China.
[Chen, Lihong] Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and GynecologyFuzhou, China.
RP Chen, L (reprint author), Fujian Medical University, The First Affiliated Hospital, Department of Obstetrics and Gynecology, Fuzhou, China.
EM wscclh@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610870
EP 1610880
DI 10.3389/pore.2023.1610870
PG 11
ER
PT J
AU Jia, G
Lei, P
Zhang, Y
Zheng, Z
Fang, J
Yang, X
Wei, H
Chen, T
AF Jia, Guiru
Lei, Purun
Zhang, Yanru
Zheng, Zongheng
Fang, Jiafeng
Yang, Xiaofeng
Wei, Hongbo
Chen, Tufeng
TI New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE left-sided colon cancer; retrieved lymph nodes; log odds of positive lymph nodes; revised nodal stage; staging system
ID left-sided colon cancer; retrieved lymph nodes; log odds of positive lymph nodes; revised nodal stage; staging system
AB Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: Wedeveloped novel TrNand TLODDS classifications for LCC patients that incorporated 7 stageswith reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), bettermodel-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.
C1 [Jia, Guiru] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Lei, Purun] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Zhang, Yanru] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Zheng, Zongheng] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Fang, Jiafeng] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Yang, Xiaofeng] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Wei, Hongbo] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
[Chen, Tufeng] Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal SurgeryGuangzhou, China.
RP Chen, T (reprint author), Sun Yat-sen University, The Third Affiliated Hospital, Department of Gastrointestinal Surgery, Guangzhou, China.
EM chentuf@mail.sysu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610874
EP 1610885
DI 10.3389/pore.2023.1610874
PG 12
ER
PT J
AU Zhao, Sh
Zhang, D
Liu, S
Huang, J
AF Zhao, Shimin
Zhang, Dongdong
Liu, Sicheng
Huang, Jun
TI The roles of NOP56 in cancer and SCA36
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE methylation; NOP56; malignant tumor; box C/D RNP; SCA36
ID methylation; NOP56; malignant tumor; box C/D RNP; SCA36
AB NOP56 is a highly conserved nucleolar protein. Amplification of the intron GGCCTG hexanucleotide repeat sequence of the NOP56 gene results in spinal cerebellar ataxia type 36 (SCA36). NOP56 contains an N-terminal domain, a coiled-coil domain, and a C-terminal domain. Nucleolar protein NOP56 is significantly abnormally expressed in a number of malignant tumors, and its mechanism is different in different tumors, but its regulatory mechanism in most tumors has not been fully explored. NOP56 promotes tumorigenesis in some cancers and inhibits tumorigenesis in others. In addition, NOP56 is associated with methylation in some tumors, suggesting that NOP56 has the potential to become a tumor-specific marker. This review focuses on the structure, function, related signaling pathways, and role of NOP56 in the progression of various malignancies, and discusses the progression of NOP56 in neurodegenerative and other diseases.
C1 [Zhao, Shimin] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Zhang, Dongdong] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Liu, Sicheng] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
[Huang, Jun] Second Affiliated Hospital of Nanchang University, Department of General SurgeryNanchang, China.
RP Huang, J (reprint author), Second Affiliated Hospital of Nanchang University, Department of General Surgery, Nanchang, China.
EM Huangjun0727@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610884
EP 1610892
DI 10.3389/pore.2023.1610884
PG 9
ER
PT J
AU Deng, H
Li, T
Wei, F
Han, W
Xu, X
Zhang, Y
AF Deng, Hongyang
Li, Tengfei
Wei, Fengxian
Han, Wei
Xu, Xiaodong
Zhang, Youcheng
TI High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bioinformatics; gastric cancer; prognostic; immune infiltration; TMEM200A
ID bioinformatics; gastric cancer; prognostic; immune infiltration; TMEM200A
AB Background: Gastric cancer (GC) is one of the global malignant tumors with high incidence and poor prognosis. Exploring new GC molecular markers is important to improve GC prognosis. Transmembrane protein 200A (TMEM200A) is a member of the family of transmembrane proteins (TMEM). This study is the first to investigate the potential function of TMEM200A and its relationship with immune infiltration in GC. Methods: The differential expression of TMEM200A was determined through the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC) curve was drawn to assess the diagnostic value of TMEM200A for GC. The relationship between TMEM200A and the clinical characteristics of patients with GC was investigated using the Wilcoxon test and the Kruskal-Wallis test. The effect of TMEM200A on overall survival (OS) was identified using the Kaplan-Meier method, the Logrank test, the univariate/multivariate Cox regression analysis, and the nomogram prediction model. The co-expressed genes and gene set enrichment analysis (GSEA) were used to explore the potential biological functions of TMEM200A. We used the Tumor Immune Estimation Resource (TIMER) database and the ssGSEA algorithm to estimate the relationship between TMEM200A and immune cell infiltration. Furthermore, we investigated the correlation of TMEM200A with immune checkpoint/immune cell surface markers using the TCGA-STAD data set. Finally, we identified prognosis-related methylation sites in TMEM200A using MethSurv. Results: TMEM200A was highly expressed in GC tissues. TMEM200A had a good diagnostic value for GC. High expression of TMEM200A may shorten the OS of GC patients and may be an independent risk factor for OS in GC patients. TMEM200A participates in the construction of a predictive model with a good predictive effect on the survival rate of GC patients at 1, 3, and 5 years. Coexpressed genes and GSEA indicated that TMEM200A may be an adhesion molecule closely associated with tumor invasion and metastasis. In addition, TMEM200A may be significantly associated with immune cell infiltration and immune checkpoint expression. We also found that TMEM200A contains three methylation sites associated with a poor prognosis. Conclusion: Upregulated TMEM200A may be a promising prognostic marker for GC and is closely associated with the tumor microenvironment (TME).
C1 [Deng, Hongyang] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Li, Tengfei] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Wei, Fengxian] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Han, Wei] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Xu, Xiaodong] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
[Zhang, Youcheng] The Second Hospital of Lanzhou University, The Department of General SurgeryLanzhou, China.
RP Zhang, Y (reprint author), The Second Hospital of Lanzhou University, The Department of General Surgery, Lanzhou, China.
EM zhangyouchengphd@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610893
EP 1610910
DI 10.3389/pore.2023.1610893
PG 18
ER
PT J
AU Lu, Ch
Feng, J
Yao, Z
Shi, L
Li, J
AF Lu, Chang
Feng, Jizhen
Yao, Zhigang
Shi, Lei
Li, Jiamei
TI Case report: Gastric adenosquamous carcinoma with EBV-positive component of squamous cell carcinoma mixed with gastric carcinoma with lymphoid stroma: A novel case report and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; gastric cancer; Epstein-Barr virus; adenosquamous carcinoma; gastric carcinoma with lymphoid stroma
ID case report; gastric cancer; Epstein-Barr virus; adenosquamous carcinoma; gastric carcinoma with lymphoid stroma
AB Background: Gastric adenosquamous carcinoma with EBV-positive component of squamous cell carcinoma mixed with gastric carcinoma with lymphoid stroma are extremely unusual variants of gastric carcinoma. We herein reported such a case and summarized five related cases that have been reported previously. Case presentation: A 59-year-old man was admitted to our hospital with upper abdominal discomfort and acid reflux. Gastric endoscopic examination revealed an irregular ulcer in the gastric angle. Biopsy of the lesion revealed adenocarcinoma. The patient underwent laparoscopic distal gastrectomy with lymph node dissection subsequently. Histologically, the tumor showed coexistence of GASC and GCLS. SCC and GCLS were positive for EBER in situ hybridization, while adenocarcinoma component was negative. Accordingly, the present case was diagnosed as GASC with EBV-positive component of SCC mixed with GCLS. Conclusion: GASC with EBV-positive component of SCC mixed with GCLS is extremely rare. Although the pathogenesis of GASC and the role of EBV in the development of an ASC component have not been fully elucidated, this case will help clinicians and pathologists better understand this special subtype of gastric tumor.
C1 [Lu, Chang] Shandong University, Shandong Provincial Hospital, Department of PathologyJinan, Shandong, China.
[Feng, Jizhen] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of RadiologyJinan, Shandong, China.
[Yao, Zhigang] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, Shandong, China.
[Shi, Lei] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of GastroenterologyJinan, Shandong, China.
[Li, Jiamei] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, Shandong, China.
RP Li, J (reprint author), Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of Pathology, Jinan, China.
EM lijiamei366@126.com
CR Kuroda N, Oonishi K, Inoue K, OharaM,Mizuno K, Lee GH. Lymphoepitheliomalike carcinoma of the stomach associated with adenosquamous carcinoma. Med Mol Morphol, 2010, 43(3):170–3., DOI 10.1007/s00795-009-0445-z
Oya HTHKT. Adenosquamous carcinoma, with a component of carcinoma with lymphoid stroma positive for EBER-1, a case report. Stomach Intestine, 2010, 45:1987–97.
Miyake H, Miyasaka C, Ishida M, Miki H, Inoue K, Tsuta K. Simultaneous gastric adenosquamous carcinoma and gastric carcinoma with lymphoid stroma: A case report. Mol Clin Oncol, 2019, 11(1):77–80., DOI 10.3892/mco.2019.1860
Cao F, Yan Y, Niu D, Huang X, Jia L, Diao X, et al. Epstein-barr virus-associated gastric adenosquamous carcinoma with concurrent gastric carcinoma with lymphoid stroma: A case report and review of the literature. Bmc Gastroenterol, 2022, 22(1):346., DOI 10.1186/s12876-022-02417-4
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610902
EP 1610907
DI 10.3389/pore.2023.1610902
PG 6
ER
PT J
AU Kong, L
Yang, M
Wan, Z
Wang, L
AF Kong, Linghong
Yang, Ming
Wan, Zhiyi
Wang, Lining
TI Cohort size required for prognostic genes analysis of stage II/III esophageal squamous cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE esophageal squamous cell carcinoma; prognostic genes analysis; power-law; events number; cohort size
ID esophageal squamous cell carcinoma; prognostic genes analysis; power-law; events number; cohort size
AB Background: Few overlaps between prognostic biomarkers are observed among different independently performed genomic studies of esophageal squamous cell carcinoma (ESCC). One of the reasons for this is the insufficient cohort size. How many cases are needed to prognostic genes analysis in ESCC? Methods: Here, based on 387 stage II/III ESCC cases analyzed by wholegenome sequencing from one single center, effects of cohort size on prognostic genes analysis were investigated. Prognostic genes analysis was performed in 100 replicates at each cohort size level using a random resampling method. Results: The number of prognostic genes followed a power-law increase with cohort size in ESCC patients with stage II and stage III, with exponents of 2.27 and 2.25, respectively. Power-law curves with increasing events number were also observed in stage II and III ESCC, respectively, and they almost overlapped. The probability of obtaining statistically significant prognostic genes shows a logistic cumulative distribution function with respect to cohort size. To achieve a 100% probability of obtaining statistically significant prognostic genes, the minimum cohort sizes required in stage II and III ESCC were approximately 95 and 60, respectively, corresponding to a number of outcome events of 33 and 36, respectively. Conclusion: In summary, the number of prognostic genes follows a power-law growth with the cohort size or events number in ESCC. The minimum events number required to achieve a 100% probability of obtaining a statistically significant prognostic gene is approximately 35.
C1 [Kong, Linghong] Beijing Chuiyangliu Hospital, Department of PathologyBeijing, China.
[Yang, Ming] Tsinghua University, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Hepato-Pancreato-Biliary CenterBeijing, China.
[Wan, Zhiyi] Beijing Chuiyangliu Hospital, Department of PathologyBeijing, China.
[Wang, Lining] Beijing Chuiyangliu Hospital, Department of PathologyBeijing, China.
RP Wang, L (reprint author), Beijing Chuiyangliu Hospital, Department of Pathology, Beijing, China.
EM wanglining1001@126.com
CR Lam AK. Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol, 2000, 33:71–90., DOI 10.1016/s1040-8428(99)00054-2
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610909
EP 1610912
DI 10.3389/pore.2023.1610909
PG 4
ER
PT J
AU Cheng, H
Zong, L
Yu, Sh
Chen, J
Wan, X
Xiang, Y
Yang, J
AF Cheng, Hongyan
Zong, Liju
Yu, Shuangni
Chen, Jie
Wan, Xirun
Xiang, Yang
Yang, Junjun
TI Expression of the immune targets in tumor-infiltrating immunocytes of gestational trophoblastic neoplasia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gestational trophoblastic neoplasia; tumor-infiltrating immunocyte; PD-1; TIM-3; GAL-9; LAG-3
ID gestational trophoblastic neoplasia; tumor-infiltrating immunocyte; PD-1; TIM-3; GAL-9; LAG-3
AB Objectives: To evaluate the expression of emerging immune targets in the tumor-infiltrating immunocytes (TIIs) of human gestational trophoblastic neoplasia (GTN) specimens, and to analyze the correlation between the expression patterns and prognosis of GTN patients. Methods: Between January 2008 and December 2017, patients who were diagnosed histologically with GTN were included in this study. The expression densities of LAG-3, TIM-3, GAL-9, PD-1, CD68, CD8, and FOXP3 in the TIIs were assessed independently by two pathologists blinded to clinical outcomes. The expression patterns and correlation with patient outcomes were analyzed to identify prognostic factors. Results: We identified 108 patients with GTN, including 67 with choriocarcinoma, 32 with placental site trophoblastic tumor (PSTT), and 9 with epithelioid trophoblastic tumor (ETT). Almost all GTN patients showed expression of GAL-9, TIM-3, and PD-1 in TIIs (100%, 92.6%, and 90.7%, respectively); LAG-3 was expressed in 77.8% of the samples. The expression densities of CD68 and GAL-9 were significantly higher in choriocarcinoma than that in PSTT and ETT. The TIM-3 expression density in choriocarcinoma was higher than that in PSTT. In addition, the expression density of LAG-3 in the TIIs of choriocarcinoma and PSTT was higher than that in ETT. There was no statistical difference in the expression pattern of PD-1 among different pathological subtypes. The positive expression of LAG- 3 in tumor TIIs was a prognostic factor for disease recurrence, and patients with positive expression of LAG-3 in the TIIs had poorer disease-free survival (p = 0.026). Conclusion: Our study evaluated the expression of immune targets PD-1, TIM-3, LAG-3, and GAL-9 in the TIIs of GTN patients and found that they were widely expressed but not associated with patients’ prognoses, excepting the positive expression of LAG-3 was a prognostic factor for disease recurrence.
C1 [Cheng, Hongyan] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Zong, Liju] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Yu, Shuangni] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of PathologyBeijing, China.
[Chen, Jie] Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Department of PathologyBeijing, China.
[Wan, Xirun] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Xiang, Yang] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Yang, Junjun] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
RP Yang, J (reprint author), Peking Union Medical College Hospital, Department of Obstetrics and Gynecology, Beijing, China.
EM yangjunjun@pumch.cn
CR Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet, 2018, 143(2):79–85., DOI 10.1002/ijgo.12615
Zong L, Yang J, Wang X, Kong Y, Ren T, Zhao J, et al. Management and prognosis of patients with liver metastases from gestational trophoblastic neoplasia: A retrospective cohort study. Cancer Manag Res, 2018, 10:557., DOI 10.2147/CMAR. S160606
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Nakashima A, Shima T, Aoki A, Kawaguchi M, Yasuda I, Tsuda S, et al. Molecular and immunological developments in placentas. Hum Immunol, 2021, 82:317–24., DOI 10.1016/j.humimm.2021.01.012
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610918
EP 1610925
DI 10.3389/pore.2023.1610918
PG 8
ER
PT J
AU Sun, A
Tian, X
Chen, Y
Yang, W
Lin, Q
AF Sun, Aiqin
Tian, Xianyan
Chen, Yifei
Yang, Wannian
Lin, Qiong
TI Emerging roles of the HECT E3 ubiquitin ligases in gastric cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE gastric cancer; ubiquitination; tumor suppressor; HECT E3 ubiquitin ligases; oncoprotein
ID gastric cancer; ubiquitination; tumor suppressor; HECT E3 ubiquitin ligases; oncoprotein
AB Gastric cancer (GC) is one of the most pernicious gastrointestinal tumors with extraordinarily high incidence and mortality. Ubiquitination modification of cellular signaling proteins has been shown to play important roles in GC tumorigenesis, progression, and prognosis. The E3 ubiquitin ligase is the crucial enzyme in the ubiquitination reaction and determines the specificity of ubiquitination substrates, and thus, the cellular effects. The HECT E3 ligases are the second largest E3 ubiquitin ligase family characterized by containing a HECT domain that has E3 ubiquitin ligase activity. The HECT E3 ubiquitin ligases have been found to engage in GC progression. However, whether HECT E3 ligases function as tumor promoters or tumor suppressors in GC remains controversial. In this review, we will focus on recent discoveries about the role of the HECT E3 ubiquitin ligases, especially members of the NEDD4 and other HECT E3 ligase subfamilies, in GC.
C1 [Sun, Aiqin] Jiangsu University, School of MedicineZhenjiang, China.
[Tian, Xianyan] Jiangsu University, School of MedicineZhenjiang, China.
[Chen, Yifei] Jiangsu University, School of MedicineZhenjiang, China.
[Yang, Wannian] Jiangsu University, School of MedicineZhenjiang, China.
[Lin, Qiong] Jiangsu University, School of MedicineZhenjiang, China.
RP Lin, Q (reprint author), Jiangsu University, School of Medicine, Zhenjiang, China.
EM qlin@ujs.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610931
EP 1610938
DI 10.3389/pore.2023.1610931
PG 8
ER
PT J
AU Bodis, F
Orosz, G
Toth, J
Szabo, M
Elo, GL
Gal, J
Elo, G
AF Bodis, Fruzsina
Orosz, Gabor
Toth, T. Jozsef
Szabo, Marcell
Elo, Gergely Laszlo
Gal, Janos
Elo, Gabor
TI Percutaneous tracheostomy: Comparison of three different methods with respect to tracheal cartilage injury in cadavers —Randomized controlled study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE percutaneous tracheostomy; tracheal cartilage injury; Tracheal stenosis; Griggs; Ciaglia Blue Rhino
ID percutaneous tracheostomy; tracheal cartilage injury; Tracheal stenosis; Griggs; Ciaglia Blue Rhino
AB Background: Performing tracheostomy improves patient comfort and success rate of weaning from prolonged invasive mechanical ventilation. Data suggest that patients have more benefit of percutaneous technique than the surgical procedure, however, there is no consensus on the percutaneous method of choice regarding severe complications such as late tracheal stenosis. Aim of this study was comparing incidences of cartilage injury caused by different percutaneous dilatation techniques (PDT), including Single Dilator, Griggs’ and modified (bidirectional) Griggs’ method. Materials and methods: Randomized observational study was conducted on 150 cadavers underwent post-mortem percutaneous tracheostomy. Data of cadavers including age, gender and time elapsed from death until the intervention (more or less than 72 h) were collected and recorded. Primary and secondary outcomes were: rate of cartilage injury and cannula malposition respectively. Results: Statistical analysis revealed that method of intervention was significantly associated with occurrence of cartilage injury, as comparing either standard Griggs’ with Single Dilator (p = 0.002; OR: 4.903; 95% CI: 1.834–13.105) or modified Griggs’ with Single Dilator (p < 0.001; OR: 6.559; 95% CI: 2.472–17.404), however, no statistical difference was observed between standard and modified Griggs’ techniques (p = 0.583; OR: 0.748; 95% CI: 0.347–1.610). We found no statistical difference in the occurrence of cartilage injury between the early- and late post-mortem group (p = 0.630). Neither gender (p = 0.913), nor age (p = 0.529) influenced the rate of cartilage fracture. There was no statistical difference between the applied PDT techniques regarding the cannula misplacement/malposition. Conclusion: In this cadaver study both standard and modified Griggs’ forceps dilatational methods were safer than Single dilator in respect of cartilage injury.
C1 [Bodis, Fruzsina] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Orosz, Gabor] Semmelweis University, Department of Anaesthesiology and Intensive TherapyBudapest, Hungary.
[Toth, T. Jozsef] Semmelweis University, Department of Anaesthesiology and Intensive TherapyBudapest, Hungary.
[Szabo, Marcell] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Elo, Gergely Laszlo] Semmelweis University, Department of Anaesthesiology and Intensive TherapyBudapest, Hungary.
[Gal, Janos] Semmelweis University, Department of Anaesthesiology and Intensive TherapyBudapest, Hungary.
[Elo, Gabor] Semmelweis University, Department of Anaesthesiology and Intensive TherapyBudapest, Hungary.
RP Bodis, F (reprint author), Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Budapest, Hungary.
EM bodis.fruzsina@med.semmelweis-univ.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610934
EP 1610941
DI 10.3389/pore.2023.1610934
PG 8
ER
PT J
AU Rubovszky, G
Kocsis, J
Boer, K
Chilingirova, N
Dank, M
Kahan, Zs
Kaidarova, D
Kover, E
Vertakova Krakovska, B
Mahr, K
Mrinakova, B
Piko, B
Bozovic-Spasojevic, I
Horvath, Zs
AF Rubovszky, Gabor
Kocsis, Judit
Boer, Katalin
Chilingirova, Nataliya
Dank, Magdolna
Kahan, Zsuzsanna
Kaidarova, Dilyara
Kover, Erika
Vertakova Krakovska, Bibiana
Mahr, Karoly
Mrinakova, Bela
Piko, Bela
Bozovic-Spasojevic, Ivana
Horvath, Zsolt
TI Corrigendum: Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE early breast cancer; locally advanced breast cancer; adjuvant treatment; neoadjuvant treatment; metastatic breast cancer; inflammatory breast cancer; guideline
ID early breast cancer; locally advanced breast cancer; adjuvant treatment; neoadjuvant treatment; metastatic breast cancer; inflammatory breast cancer; guideline
AB A Corrigendum on Systemic treatment of breast cancer. 1st Central-Eastern European professional consensus statement on breast cancer by Rubovszky G, Kocsis J, Boer K, Chilingirova N, Dank M, Kahan Z, Kaidarova D, Kover E, Krakovska BV, Mahr K, Mrinakova B, Piko B, Bozovic-Spasojevic I and Horvath Z (2022). Pathol. Oncol. Res. 28:1610383. doi: 10.3389/pore.2022.1610383
C1 [Rubovszky, Gabor] Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai OsztalyBudapest, Hungary.
[Kocsis, Judit] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
[Boer, Katalin] St. Margit Hospital, Clinical Oncology DepartmentBudapest, Hungary.
[Chilingirova, Nataliya] Medical University-Pleven, Heart and Brain Hospital, Science and Research Institute, Clinic Center of ExcellencePleven, Bulgaria.
[Dank, Magdolna] Semmelweis University, Department of OncologyBudapest, Hungary.
[Kahan, Zsuzsanna] University of Szeged, Department of OncotherapySzeged, Hungary.
[Kaidarova, Dilyara] Kazakh Institute of Oncology and RadiologyAlmaty, Kazakhstan.
[Kover, Erika] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Vertakova Krakovska, Bibiana] Comenius University, Faculty of Medicine, 1st Department of OncologyBratislava, Slovakia.
[Mahr, Karoly] Zala Megyei Szent Rafael Korhaz, OnkologiaZalaegerszeg, Hungary.
[Mrinakova, Bela] Comenius University, Faculty of Medicine, 1st Department of OncologyBratislava, Slovakia.
[Piko, Bela] Bekes Megyei Kozponti Korhaz, Pandy Kalman Tagkorhaz, Megyei Onkologiai CentrumGyula, Hungary.
[Bozovic-Spasojevic, Ivana] Daily Chemotherapy HospitalBelgrade, Serbia.
[Horvath, Zsolt] Bacs-Kiskun County Hospital, Department of OncoradiologyKecskemet, Hungary.
RP Rubovszky, G (reprint author), Orszagos Onkologiai Intezet, „B” Belgyogyaszati-Onkologiai es Klinikai Farmakologiai Osztaly, Budapest, Hungary.
EM rubovszkyg@gmail.com
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610954
EP 1610955
DI 10.3389/pore.2023.1610954
PG 2
ER
PT J
AU Yang, Y
Wang, Z
He, M
Diao, L
Yu, B
Li, D
AF Yang, Yuting
Wang, Ze
He, Mengqi
Diao, Lihong
Yu, Biyue
Li, Dong
TI NAD+ biosynthesis metabolism predicts prognosis and indicates immune microenvironment for breast cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; breast cancer; prognosis; immune microenvironment; NAD+ biosynthesis
ID immunotherapy; breast cancer; prognosis; immune microenvironment; NAD+ biosynthesis
AB The growing evidence implies that tumor cells need to increase NAD+ levels by upregulating NAD+ biosynthesis to satisfy their growth demand. NAD+ biosynthesis metabolism is implicated in tumor progression. Breast cancer (BC) is the most common malignant malignancy in the world. Nevertheless, the prognostic significance of NAD+ biosynthesis and its relationship with the tumor immune microenvironment in breast cancer still need further investigation. In this study, we obtained the mRNA expression data and clinical information of BC samples from public databases and calculated the level of NAD+ biosynthesis activity by single-sample gene set enrichment analysis (ssGSEA). We then explored the relationship between the NAD+ biosynthesis score, infiltrating immune cells, prognosis significance, immunogenicity and immune checkpoint molecules. The results demonstrated that patients with high NAD+ biosynthetic score displayed poor prognosis, high immune infiltration, high immunogenicity, elevated PDL1 expression, and might more benefit from immunotherapy. Taken together, our studies not only deepened the understanding of NAD+ biosynthesis metabolism of breast cancer but also provided new insights into personalized treatment strategies and immunological therapies to improve the outcomes of breast cancer patients.
C1 [Yang, Yuting] Medical College of Qingdao University, Department of ImmunologyQingdao, Shandong, China.
[Wang, Ze] Beijing Institute of Lifeomics, National Center for Protein Sciences, State Key Laboratory of Proteomics, Beijing Proteome Research CenterBeijing, China.
[He, Mengqi] Beijing Institute of Lifeomics, National Center for Protein Sciences, State Key Laboratory of Proteomics, Beijing Proteome Research CenterBeijing, China.
[Diao, Lihong] Beijing University of Chinese Medicine, School of Traditional Chinese MedicineBeijing, China.
[Yu, Biyue] Hebei University, School of Life SciencesBaoding, Hebei, China.
[Li, Dong] Medical College of Qingdao University, Department of ImmunologyQingdao, Shandong, China.
RP Li, D (reprint author), Medical College of Qingdao University, Department of Immunology, Qingdao, China.
EM lidong.bprc@foxmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610956
EP 1610967
DI 10.3389/pore.2023.1610956
PG 12
ER
PT J
AU Chen, H
Shi, X
Ren, L
Wan, Y
Zhuo, H
Zeng, L
SangDan, W
Wang, F
AF Chen, HongMin
Shi, XiaoXiao
Ren, Li
Wan, YuMing
Zhuo, HongYu
Zeng, Li
SangDan, WangMu
Wang, Feng
TI Screening of core genes and prediction of ceRNA regulation mechanism of circRNAs in nasopharyngeal carcinoma by bioinformatics analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TCGA; nasopharyngeal carcinoma; weighted gene co-expression network analysis; GEO database; fibronectin 1
ID TCGA; nasopharyngeal carcinoma; weighted gene co-expression network analysis; GEO database; fibronectin 1
AB Background: Nasopharyngeal carcinoma (NPC) represents a highly aggressive malignant tumor. Competing endogenous RNAs (ceRNA) regulation is a common regulatory mechanism in tumors. The ceRNA network links the functions between mRNAs and ncRNAs, thus playing an important regulatory role in diseases. This study screened the potential key genes in NPC and predicted regulatory mechanisms using bioinformatics analysis. Methods: The merged microarray data of three NPC-related mRNA expression microarrays from the Gene Expression Omnibus (GEO) database and the expression data of tumor samples or normal samples from the nasopharynx and tonsil in The Cancer Genome Atlas (TCGA) database were both subjected to differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The results from two different databases were intersected with WGCNA results to obtain potential regulatory genes in NPC, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The hub-gene in candidate genes was discerned through Protein-Protein Interaction (PPI) analysis and its upstream regulatory mechanism was predicted by miRwalk and circbank databases. Results: Totally 68 upregulated genes and 96 downregulated genes in NPC were screened through GEO and TCGA. According to WGCNA, the NPCrelated modules were screened from GEO and TCGA analysis results, and the genes in the modules were obtained. After the results of differential analysis and WGCNA were intersected, 74 differentially expressed candidate genes associated with NPC were discerned. Finally, fibronectin 1 (FN1) was identified as a hub-gene in NPC. Prediction of upstream regulatory mechanisms of FN1 suggested that FN1 may be regulated by ceRNA mechanisms involving multiple circRNAs, thereby influencing NPC progression through ceRNA regulation. Conclusion: FN1 is identified as a key regulator in NPC development and is likely to be regulated by numerous circRNA-mediated ceRNA mechanisms.
C1 [Chen, HongMin] Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical OncologySichuan, China.
[Shi, XiaoXiao] Sichuan University, West China Hospital, Chengdu Shangjin Nanfu Hospital, Department of Medical OncologyChengdu, China.
[Ren, Li] Sichuan University, West China Hospital, Cancer Center, Department of Thoracic OncologyChengdu, China.
[Wan, YuMing] Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical OncologySichuan, China.
[Zhuo, HongYu] Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical OncologySichuan, China.
[Zeng, Li] Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical OncologySichuan, China.
[SangDan, WangMu] People’s Hospital of Tibet Autonomous Region, Department of OncologyLhasa, China.
[Wang, Feng] Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical OncologySichuan, China.
RP Wang, F (reprint author), Medical School, Sichuan University, West China Hospital, Cancer Center, Department of Medical Oncology, Sichuan, China.
EM wangfeng5024@126.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610960
EP 1610971
DI 10.3389/pore.2023.1610960
PG 12
ER
PT J
AU Cao, X
Wu, B
Guo, Sh
Zhong, W
Zhu, Sh
Zhang, Z
Gu, L
Li, H
AF Cao, Xiying
Wu, Bingqun
Guo, Shaoming
Zhong, Weixiang
Zhu, Shenyu
Zhang, Zuxiong
Gu, Liang
Li, Hui
TI APOC1 predicts a worse prognosis for esophageal squamous cell carcinoma and is associated with tumor immune infiltration during tumorigenesis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE bioinformatics; prognosis; expression; APOC1; ESCA
ID bioinformatics; prognosis; expression; APOC1; ESCA
AB Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/ TISIDB/) website, and various other analysis tools. Results: In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues (p < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan–Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) (p = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) (p = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC (p = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, Staphylococcus aureus infection, antigen processing and presentation, and graft-versus-host disease (all p < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. Conclusion: APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.
C1 [Cao, Xiying] Capital Medical University, Beijing Chao-Yang Hospital, Department of Thoracic SurgeryBeijing, China.
[Wu, Bingqun] First Hospital of Tsinghua University Beijing, Huaxin Hospital, Department of Thoracic SurgeryBeijing, China.
[Guo, Shaoming] The First Affiliated Hospital of Gannan Medical University, Department of Thoracic SurgeryGanzhou, Jiangxi, China.
[Zhong, Weixiang] The First Affiliated Hospital of Gannan Medical University, Department of Thoracic SurgeryGanzhou, Jiangxi, China.
[Zhu, Shenyu] The First Affiliated Hospital of Gannan Medical University, Department of Thoracic SurgeryGanzhou, Jiangxi, China.
[Zhang, Zuxiong] The First Affiliated Hospital of Gannan Medical University, Department of Thoracic SurgeryGanzhou, Jiangxi, China.
[Gu, Liang] The First Affiliated Hospital of Gannan Medical University, Department of Thoracic SurgeryGanzhou, Jiangxi, China.
[Li, Hui] Capital Medical University, Beijing Chao-Yang Hospital, Department of Thoracic SurgeryBeijing, China.
RP Li, H (reprint author), Capital Medical University, Beijing Chao-Yang Hospital, Department of Thoracic Surgery, Beijing, China.
EM huilee@vip.sina.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610976
EP 1610990
DI 10.3389/pore.2023.1610976
PG 15
ER
PT J
AU Zhao, N
Mei, N
Yi, Y
Wang, H
Wang, Y
Yao, Y
Li, Ch
AF Zhao, Ni
Mei, Nan
Yi, Ye
Wang, Hongyan
Wang, Yajian
Yao, Yu
Li, Chunli
TI Case report: Pathological and genetic features of pancreatic undifferentiated carcinoma with osteoclast-like giant cells
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE prognosis; pathological features; undifferentiated carcinoma; osteoclast-like giant cells; pancreatic carcinoma
ID prognosis; pathological features; undifferentiated carcinoma; osteoclast-like giant cells; pancreatic carcinoma
AB Objectives: Pancreatic undifferentiated carcinoma accounts for 2%–7% of pancreatic carcinomas. We aimed to investigate the pathological and genetic characteristics of pancreatic undifferentiated carcinoma with osteoclast-like giant cells and the key points of treatment. Methods: The clinical data and follow-up results of four patients diagnosed with pancreatic undifferentiated carcinoma with osteoclast-like giant cells between May 2015 and May 2020 at the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed. Results: Chief complaints included “pain and discomfort in the upper abdomen” (2/4), “nausea and vomiting” (1/4) or no symptoms (1/4). Preoperative mildly elevated tumor markers included carcinoembryonic antigen (1/4) and CA19-9 (1/4). The tumors were located in the tail of the pancreas in three patients and the head and neck in one patient. Tumor metastasis was found in pancreatic adipose tissue in two patients and lymph node metastasis in one patient, with microscopic heterogeneous mononuclear cells and scattered osteoclast-like giant cells of various sizes. One patient (1/4) had a mucinous cystic tumor of the pancreas, and two patients (2/4) had adenocarcinoma of the pancreatic duct. Only one patient received postoperative gemcitabine combined with albuminbound paclitaxel chemotherapy. Conclusion: Currently, treatment guidelines are lacking for PUC-OGC, and prognosis varies markedly. More cases must be reported to clarify its origination. The long-term follow-up of diagnosed patients and genetic mutation testing can also contribute to improving treatment and prognosis of this disease.
C1 [Zhao, Ni] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical OncologyXi’an, Shaanxi, China.
[Mei, Nan] The First Affiliated Hospital of Xi’an Jiaotong University, Department of HematologyXi’an, Shaanxi, China.
[Yi, Ye] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical OncologyXi’an, Shaanxi, China.
[Wang, Hongyan] The First Affiliated Hospital of Xi’an Jiaotong University, Department of PathologyXi’an, Shaanxi, China.
[Wang, Yajian] The First Affiliated Hospital of Xi’an Jiaotong University, Department of PathologyXi’an, Shaanxi, China.
[Yao, Yu] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical OncologyXi’an, Shaanxi, China.
[Li, Chunli] The First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical OncologyXi’an, Shaanxi, China.
RP Li, Ch (reprint author), The First Affiliated Hospital of Xi’an Jiaotong University, Department of Medical Oncology, Xi’an, China.
EM chunli5158@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610983
EP 1610993
DI 10.3389/pore.2023.1610983
PG 11
ER
PT J
AU Ma, YT
Li, Y
Yan, L
Hua, F
Wang, DG
Xu, GY
Yang, HL
Xue, YJ
Qin, YJ
Sha, D
Ning, H
Zhao, MQ
Yao, ZG
AF Ma, Yu-Ting
Li, Yan
Yan, Li
Hua, Fang
Wang, Dong-Guan
Xu, Guo-Ying
Yang, Hong-Lan
Xue, Ying-Jie
Qin, Ye-Jun
Sha, Dan
Ning, Hao
Zhao, Miao-Qing
Yao, Zhi-Gang
TI Corrigendum: Case report: Potential predictive value of MMR/MSI status and PD-1 expression in immunotherapy for urothelial carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE immunotherapy; microsatellite instability; immune checkpoint inhibitors; urothelial carcinoma; lynch syndrome; PD-1/PD-L1
ID immunotherapy; microsatellite instability; immune checkpoint inhibitors; urothelial carcinoma; lynch syndrome; PD-1/PD-L1
AB A Corrigendum on Case report: Potential predictive value of MMR/MSI status and PD-1 expression in immunotherapy for urothelial carcinoma by Ma Y-T, Li Y, Yan L, Hua F, Wang D-G, Xu G-Y, Yang H-L, Xue Y-J, Qin Y-J, Sha D, Ning H, Zhao M-Q and Yao Z-G (2022). Pathol Oncol Res. 28:1610638. doi: 10.3389/pore.2022. 1610638
C1 [Ma, Yu-Ting] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Li, Yan] Dongying City People’s Hospital, Department of OncologyDongying, China.
[Yan, Li] Dongying City People’s Hospital, Department of PathologyDongying, China.
[Hua, Fang] Tulane University, Department of Microbiology and ImmunologyNew Orleans, LA, USA.
[Wang, Dong-Guan] Dongying City People’s Hospital, Department of PathologyDongying, China.
[Xu, Guo-Ying] Dongying Hospital of Traditional Chinese Medicine, Department of Urology SurgeryDongying, China.
[Yang, Hong-Lan] Dongying City People’s Hospital, Department of OncologyDongying, China.
[Xue, Ying-Jie] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Qin, Ye-Jun] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Sha, Dan] Shandong Lung Cancer Institute, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of OncologyJinan, China.
[Ning, Hao] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of UrologyJinan, China.
[Zhao, Miao-Qing] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
[Yao, Zhi-Gang] Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of PathologyJinan, China.
RP Yao, ZG (reprint author), Shandong Provincial Hospital Affiliated to Shandong First Medical University, Department of Pathology, Jinan, China.
EM zhaomqsd@163.com
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610989
EP 1610989
DI 10.3389/pore.2023.1610989
PG 1
ER
PT J
AU Sztankovics, D
Moldvai, D
Petovari, G
Gelencser, R
Krencz, I
Raffay, R
Danko, T
Sebestyen, A
AF Sztankovics, Daniel
Moldvai, Dorottya
Petovari, Gabor
Gelencser, Rebeka
Krencz, Ildiko
Raffay, Regina
Danko, Titanilla
Sebestyen, Anna
TI 3D bioprinting and the revolution in experimental cancer model systems—A review of developing new models and experiences with in vitro 3D bioprinted breast cancer tissue-mimetic structures
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cancer; breast cancer; 3D bioprinting; disease models; biofabrication
ID cancer; breast cancer; 3D bioprinting; disease models; biofabrication
AB Growing evidence propagates those alternative technologies (relevant human cell-based—e.g., organ-on-chips or biofabricated models—or artificial intelligence-combined technologies) that could help in vitro test and predict human response and toxicity in medical research more accurately. In vitro disease model developments have great efforts to create and serve the need of reducing and replacing animal experiments and establishing human cell-based in vitro test systems for research use, innovations, and drug tests. We need human cell-based test systems for disease models and experimental cancer research; therefore, in vitro three-dimensional (3D) models have a renaissance, and the rediscovery and development of these technologies are growing ever faster. This recent paper summarises the early history of cell biology/cellular pathology, cell-, tissue culturing, and cancer research models. In addition, we highlight the results of the increasing use of 3D model systems and the 3D bioprinted/biofabricated model developments. Moreover, we present our newly established 3D bioprinted luminal B type breast cancer model system, and the advantages of in vitro 3D models, especially the bioprinted ones. Based on our results and the reviewed developments of in vitro breast cancer models, the heterogeneity and the real in vivo situation of cancer tissues can be represented better by using 3D bioprinted, biofabricated models. However, standardising the 3D bioprinting methods is necessary for future applications in different high-throughput drug tests and patient-derived tumour models. Applying these standardised new models can lead to the point that cancer drug developments will be more successful, efficient, and consequently costeffective in the near future.
C1 [Sztankovics, Daniel] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Moldvai, Dorottya] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Gelencser, Rebeka] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Raffay, Regina] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Sebestyen, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM hsebanna@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1610996
EP 1611017
DI 10.3389/pore.2023.1610996
PG 22
ER
PT J
AU Zhang, Y
Li, Y
Zuo, Z
Li, T
An, Y
Zhang, W
AF Zhang, Yu
Li, Yan
Zuo, Zan
Li, Ting
An, Ying
Zhang, Wenjing
TI An epithelial–mesenchymal transition-related mRNA signature associated with the prognosis, immune infiltration and therapeutic response of colon adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE epithelial-mesenchymal transition; bioinformatics; prognostic signature; tumor immune microenvironment; colon adenocarcinoma
ID epithelial-mesenchymal transition; bioinformatics; prognostic signature; tumor immune microenvironment; colon adenocarcinoma
AB Background: Epithelial-mesenchymal transition (EMT) is closely associated with cancer cell metastasis. Colon adenocarcinoma (COAD) is one of the most common malignancies in the world, and its metastasis leading to poor prognosis remains a challenge for clinicians. The purpose of this study was to explore the prognostic value of EMT-related genes (EMTRGs) by bioinformatics analysis and to develop a new EMTRGs prognostic signature for COAD. Methods: The TCGA-COAD dataset was downloaded from the TCGA portal as the training cohort, and the GSE17538 and GSE29621 datasets were obtained from the GEO database as the validation cohort. The best EMTRGs prognostic signature was constructed by differential expression analysis, Cox, and LASSO regression analysis. Gene set enrichment analysis (GSEA) is used to reveal pathways that are enriched in high-risk and low-risk groups. Differences in tumor immune cell levels were analyzed using microenvironmental cell population counter and single sample gene set enrichment analysis. Subclass mapping analysis and Genomics of Drug Sensitivity in Cancer were applied for prediction of immunotherapy response and chemotherapy response, respectively. Results: A total of 77 differentially expressed EMTRGs were identified in the TCGA-COAD cohort, and they were significantly associated with functions and pathways related to cancer cell metastasis, proliferation, and apoptosis. We constructed EMTRGs prognostic signature with COMP, MYL9, PCOLCE2, SCG2, and TIMP1 as new COAD prognostic biomarkers. The high-risk group had a poorer prognosis with enhanced immune cell infiltration. The GSEA demonstrated that the high-risk group was involved in “ECM Receptor Interaction,” “WNT Signaling Pathway” and “Colorectal Cancer.” Furthermore, patients with high risk scores may respond to anti-CTLA4 therapy and may be more resistant to targeted therapy agents BI 2536 and ABT-888. Conclusion: Together, we developed a new EMTRGs prognostic signature that can be an independent prognostic factor for COAD. This study has guiding implications for individualized counseling and treatment of COAD patients.
C1 [Zhang, Yu] First People’s Hospital of Yunnan Province, Department of GastroenterologyKunming, China.
[Li, Yan] First People’s Hospital of Yunnan Province, Department of GastroenterologyKunming, China.
[Zuo, Zan] First People’s Hospital of Yunnan Province, Department of GastroenterologyKunming, China.
[Li, Ting] First People’s Hospital of Yunnan Province, Department of GastroenterologyKunming, China.
[An, Ying] First People’s Hospital of Yunnan Province, Department of GastroenterologyKunming, China.
[Zhang, Wenjing] Kunming University of Science and Technology, Faculty of MedicineKunming, China.
RP Zhang, W (reprint author), Kunming University of Science and Technology, Faculty of Medicine, Kunming, China.
EM wenjing_zhang1@163.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611016
EP 1611029
DI 10.3389/pore.2023.1611016
PG 14
ER
PT J
AU Zheng, Y
Li, Z
Wang, Y
Chen, W
Lin, Y
Guo, J
Ye, G
AF Zheng, Ying
Li, Zhe
Wang, Yao
Chen, Wanjiao
Lin, Yifan
Guo, Junming
Ye, Guoliang
TI CircRNA: A new class of targets for gastric cancer drug resistance therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE gastric cancer; drug resistance; circular RNA; therapeutic target; biogenesis
ID gastric cancer; drug resistance; circular RNA; therapeutic target; biogenesis
AB Gastric cancer (GC) is one of the most common malignancies worldwide. Patients with advanced GC need palliative care to ensure survival. This includes the use of chemotherapy agents, such as cisplatin, 5- fluorouracil, oxaliplatin, paclitaxel, and pemetrexed, as well as targeted agents. However, the emergence of drug resistance evidence in poor patient outcomes and poor prognosis is a motivation to determine the specific mechanism of drug resistance. Interestingly, circular RNAs (circRNAs) play an important part in the carcinogenesis and progression of GC and are involved in GC drug resistance. This review systematically summarizes the functions and mechanisms of circRNAs underlying GC drug resistance, especially chemoresistance. It also emphasizes that circRNAs can serve as promising targets for improving drug resistance and therapeutic efficacy.
C1 [Zheng, Ying] Ningbo University School of Medicine, Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of PathophysiologyNingbo, China.
[Li, Zhe] The Affiliated Hospital of Medical School of Ningbo University, Department of GastroenterologyNingbo, China.
[Wang, Yao] Ningbo University School of Medicine, Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of PathophysiologyNingbo, China.
[Chen, Wanjiao] The Affiliated Hospital of Medical School of Ningbo University, Department of GastroenterologyNingbo, China.
[Lin, Yifan] The Affiliated Hospital of Medical School of Ningbo University, Department of GastroenterologyNingbo, China.
[Guo, Junming] Ningbo University School of Medicine, Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of PathophysiologyNingbo, China.
[Ye, Guoliang] The Affiliated Hospital of Medical School of Ningbo University, Department of GastroenterologyNingbo, China.
RP Ye, G (reprint author), The Affiliated Hospital of Medical School of Ningbo University, Department of Gastroenterology, Ningbo, China.
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611033
EP 1611042
DI 10.3389/pore.2023.1611033
PG 10
ER
PT J
AU Wang, H
Yang, L
Li, Q
Song, H
Ji, H
AF Wang, Hongyu
Yang, Liqun
Li, Qiuyao
Song, Haiyun
Ji, Hong
TI Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE next-generation sequencing; classical Hodgkin lymphoma; mantle cell lymphoma; composite lymphoma; histogenesis
ID next-generation sequencing; classical Hodgkin lymphoma; mantle cell lymphoma; composite lymphoma; histogenesis
AB Composite mantle cell lymphoma and classical Hodgkin lymphoma is very rare and the actual origin of it is still unclear. Here we reported a new case of composite mantle cell lymphoma and classical Hodgkin lymphoma and analyzed its molecular changes. Eight mutations were identified in its Hodgkin component through next-generation sequencing. In addition, we reviewed the published cases of composite mantle cell lymphoma and classical Hodgkin lymphoma and summarized the molecular changes of reported cases as well as the current case to explore the possible pathway of histogenesis.
C1 [Wang, Hongyu] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of PathologyQingdao, China.
[Yang, Liqun] Chengdu Huayin Medical Laboratory Center, Huayin Health Hematopathology Comprehensive Diagnostic CenterChengdu, China.
[Li, Qiuyao] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of PathologyQingdao, China.
[Song, Haiyun] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of PathologyQingdao, China.
[Ji, Hong] Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of PathologyQingdao, China.
RP Ji, H (reprint author), Shandong University, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Department of Pathology, Qingdao, China.
EM hezejihong@163.com
CR Kuppers R, Duhrsen U, Hansmann ML. Pathogenesis, diagnosis and treatment of composite lymphomas. Lancet Oncol, 2014, 15:e435–46., DOI 10.1016/S1470-2045(14)70153-6
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Tinguely M, Rosenquist R, Sundstro¨m C, Amini R, Ku¨ppers R, Hansmann M, et al. Analysis of a clonally related mantle cell and Hodgkin lymphoma indicates Epstein–Barr virus infection of a Hodgkin/Reed–Sternberg cell precursor in a germinal center. Am J Surg Pathol, 2003, 27:1483–8., DOI 10.1097/00000478-200311000-00014
Hayes SJ, Banerjee SS, Cook Y, Houghton JB, Menasce LP. Composite mantlecell lymphoma and classical Hodgkin lymphoma. Histopathology, 2006, 48:621–3., DOI 10.1111/j.1365-2559.2005.02296.x
Stefanie S, Barbara C, Markus S, Stefano A, Sylvia H, Martin-Leo H, et al. Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B-cell-derived mantle cell lymphoma. Int J Cancer, 2014, 134:832–43., DOI 10.1002/ijc.28422
Giua R, Fontana D, Deda G, Bianchi A, Rabitti C, Incalzi R, et al. Composite mantle-cell lymphoma and classical Hodgkin lymphoma in a very old adult. J Am Geriatr Soc, 2015, 63:824–6., DOI 10.1111/jgs.13355
Ciara M, Fiona Q, Gyorgy I, Walker J, Castriciano G, O’Sullivan P, et al. Composite blastoid variant of mantle cell lymphoma and classical Hodgkin lymphoma. Int J Surg Pathol, 2017, 25:281–6., DOI 10.1177/1066896916672556
Sharma S, Singh V, Bisaria D, Tangri R. Composite lymphoma comprisingmantle cell lymphoma and epstein-barr virus positive classic Hodgkin lymphoma: A rare case. Indian J Pathol Microbiol, 2019, 62:488–90., DOI 10.4103/IJPM.IJPM_34_18
Liang G, Jing B, Weikai Y, Xiumei D, Zhuang T, Jingna G, et al. Composite mantle cell lymphoma and classical Hodgkin lymphoma: Report of a case. Chin J Pathol, 2019, 48:409–10., DOI 10.3760/cma.j.issn.0529-5807.2019.05.018
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611051
EP 1611056
DI 10.3389/pore.2023.1611051
PG 6
ER
PT J
AU Chen, Y
Ma, T
AF Chen, Yan
Ma, Tao
TI LAMP5 may promote MM progression by activating p38
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apoptosis; recurrence; prognosis; multiple myeloma; LAMP5
ID apoptosis; recurrence; prognosis; multiple myeloma; LAMP5
AB Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing onMMcell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MMprogression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.
C1 [Chen, Yan] The Affiliated Hospital of Southwest Medical University, Department of HematologyLuzhou, China.
[Ma, Tao] The Affiliated Hospital of Southwest Medical University, Department of HematologyLuzhou, China.
RP Ma, T (reprint author), The Affiliated Hospital of Southwest Medical University, Department of Hematology, Luzhou, China.
EM matao1990@swmu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611083
EP 1611094
DI 10.3389/pore.2023.1611083
PG 12
ER
PT J
AU Boniface, Ch
Spellman, P
AF Boniface, T. Christopher
Spellman, T. Paul
TI Corrigendum: Blood, toil, and taxoteres: Biological determinants of treatment-induced ctDNA dynamics for interpreting tumor response
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE biomarkers; liquid biopsy; circulating tumor DNA; ctDNA; tumor growth; treatment response
ID biomarkers; liquid biopsy; circulating tumor DNA; ctDNA; tumor growth; treatment response
AB In the published article, there were two typographical errors in the article title. Instead of “Blood, toil, and taxoteres: Biological determinates of treatment-induce ctDNA dynamics for interpreting tumor response.” It should be “Blood, toil, and taxoteres: Biological determinants of treatment-induced ctDNA dynamics for interpreting tumor response.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
C1 [Boniface, T. Christopher] Oregon Health & Science University, Knight Cancer InstitutePortland, OR, USA.
[Spellman, T. Paul] Oregon Health & Science University, Knight Cancer InstitutePortland, OR, USA.
RP Spellman, P (reprint author), Oregon Health & Science University, Knight Cancer Institute, Portland, USA.
EM spellmap@ohsu.edu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611133
EP 1611133
DI 10.3389/pore.2023.1611133
PG 1
ER
PT J
TI Editorial: Liquid biopsy—A great hope or just hype?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Editorial
DE liquid biopsy; ctDNA; circulating tumor cells; exosomes; monitoring
ID liquid biopsy; ctDNA; circulating tumor cells; exosomes; monitoring
AB Editorial on the Special Issue Liquid biopsy—A great hope or just hype?
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2023
VL 29
IS 1
BP 1611170
EP 1611172
DI 10.3389/pore.2023.1611170
PG 3
ER
PT J
AU Sun, J
Sun, Y
Miniderima,
Wang, X
AF Sun, Jiayang
Sun, Yushu
Miniderima,
Wang, Xiumei
TI Cytokine-induced killer cell treatment is superior to chemotherapy alone in esophageal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE esophageal cancer; immunotherapy; cytokine-induced killer cells; dendritic cells; network meta-analysis
ID esophageal cancer; immunotherapy; cytokine-induced killer cells; dendritic cells; network meta-analysis
AB Background: The therapeutic efficacy of cytokine-induced killer (CIK) cells versus dendritic cells (DC) co-cultured with CIK cells (DC-CIK) in treating esophageal cancer (EC) remains unclear due to the absence of a direct comparison of these two regimens. This study evaluated the comparative efficacy and safety of CIK cells versus DC-CIK using network meta-analysis in treating EC. Material and methods: We identified eligible studies from previous metaanalyses, then conducted an updated search to retrieve additional trials between February 2020 and July 2021. The primary outcomes included overall survival (OS), objective response rate (ORR), and disease control rate (DCR), and the secondary outcomes included quality of life improved rate (QLIR) and adverse events (AEs). A network meta-analysis of 12 studies was conducted using ADDIS software. Results: Twelve studies were identified, including six comparing CIK or DC-CIK plus chemotherapy (CT) with CT alone. Immunotherapy plus CT significantly improved overall survival (OS) (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.23–13.69), objective response rate (ORR) (OR 2.72, 95% CI 1.79–4.11), disease control rate (DCR) (OR 3.45, 95% CI 2.32–5.14), and quality of life improvement rate (QLIR) (OR 3.54, 95% CI 2.31–5.41). DC-CIK+CT decreased the risk of leukopenia compared with CT alone. However, no statistical difference was detected between CIK-CT and DC-CIK+CT. Conclusion: Based on the available evidence, we concluded that CIK cell treatment is superior to CT alone, but CIK-CT and DC-CIK+CT may be comparable in treating EC. However, comparing CIK-CT and DC-CIK+CT is only based on indirect evidence, so it is undoubtedly necessary to conduct studies to compare CIK-CT with DC-CIK+CT in EC patients directly.
C1 [Sun, Jiayang] Affiliated Hospital of Inner Mongolia Medical University, Department of Thoracic SurgeryHohhot, Inner Mongolia, China.
[Sun, Yushu] Inner Mongolia Cancer Hospital and Affiliated People’s Hospital of Inner Mongolia Medical University, Department of OncologyHohhot, Inner Mongolia, China.
[Miniderima, ] Inner Mongolia Cancer Hospital and Affiliated People’s Hospital of Inner Mongolia Medical University, Department of OncologyHohhot, Inner Mongolia, China.
[Wang, Xiumei] Inner Mongolia Cancer Hospital and Affiliated People’s Hospital of Inner Mongolia Medical University, Department of OncologyHohhot, Inner Mongolia, China.
RP Wang, X (reprint author), Inner Mongolia Cancer Hospital and Affiliated People’s Hospital of Inner Mongolia Medical University, Department of Oncology, Hohhot, China.
EM wangxiumei75@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610710
EP 1610719
DI 10.3389/pore.2023.1610710
PG 10
ER
PT J
AU Liu, Yh
Meng, R
Zhu, B
Zhan, Qq
Yang, X
Ding, Gy
Jia, Chl
Liu, Qy
Xu, Wg
AF Liu, Yu-hang
Meng, Rui
Zhu, Bing
Zhan, Qi-qi
Yang, Xin
Ding, Guan-yi
Jia, Chun-liang
Liu, Qian-yu
Xu, Wei-guo
TI Integrated oxidative stress score for predicting prognosis in stage III gastric cancer undergoing surgery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; oxidative stress; albumin; bilirubin; blood urea nitrogen
ID gastric cancer; oxidative stress; albumin; bilirubin; blood urea nitrogen
AB Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher’s precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram’s predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.
C1 [Liu, Yu-hang] North China University of Science and Technology, School of Clinical MedicineTangshan, China.
[Meng, Rui] Tongji University, Yangpu Hospital, Department of Emergency Intensive Care UnitShanghai, China.
[Zhu, Bing] Tangshan Gongren HospitalTangshan, China.
[Zhan, Qi-qi] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
[Yang, Xin] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
[Ding, Guan-yi] Tangshan Gongren HospitalTangshan, China.
[Jia, Chun-liang] Tangshan People’s HospitalTangshan, China.
[Liu, Qian-yu] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
[Xu, Wei-guo] North China University of Science and Technology, Affiliated Tangshan Gongren HospitalTangshan, China.
RP Xu, Wg (reprint author), North China University of Science and Technology, Affiliated Tangshan Gongren Hospital, Tangshan, China.
EM xwg853@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610897
EP 1610909
DI 10.3389/pore.2023.1610897
PG 13
ER
PT J
AU Zuo, Y
Leng, G
Leng, P
AF Zuo, Yanhua
Leng, Guangyi
Leng, Ping
TI Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; lung adenocarcinoma; tumor microenvironment; prognostic signature; neutrophil extracellular traps
ID immunotherapy; lung adenocarcinoma; tumor microenvironment; prognostic signature; neutrophil extracellular traps
AB Background: Neutrophil Extracellular Traps (NETs) are fibrous networks made of DNA-histone complexes and proteins protruded from activated neutrophils. Accumulating evidences have highlighted the vital role of NETs in tumor progression and diffusion. However, limited systematic studies regarding the role of NETs in LUAD have been performed. Methods: Differentially expressed NETs-related genes and their mutation landscape were identified with TCGA database. Consensus clustering analysis was performed to determine the NETs-related subtypes of LUAD. LASSO algorithm was employed to construct a prognostic signature. Moreover, GSE30219 and GSE31210 were used as independent validation. We also constructed a lncRNA-miRNA-mRNA regulatory axis with several miRNA and lncRNA databases. Results: Consensus clustering identified two NETs-related clusters in LUAD. High NETs score was correlated with a favorable overall survival, abundant immune cell infiltration, and high activity of immune response signal pathways. Six NET-related genes (G0S2, KCNJ15, S100A12, AKT2, CTSG, and HMGB1) with significant prognostic value were screened to develop a prognostic signature. LUAD patients with low-risk had a significantly favorable overall survival both in the training set and validation set. Moreover, NETs-related risk score and clinical stage could act as an independent prognostic factor for LUAD patients. Significant correlation was obtained between risk score and tumor immune microenvironment. We also identified lncRNA BCYRN1/miR-3664-5p/CTSG regulatory axis that may be involved in the progression of LUAD. Conclusion: We developed two molecular subtypes and a prognostic signature for LUAD based on NETs-related genes. This stratification could provide more evidences for estimating the prognosis and immunotherapy of LAUD patients.
C1 [Zuo, Yanhua] The Affiliated Hospital of Qingdao University, Department of PharmacyQingdao, China.
[Leng, Guangyi] Shenyang Pharmaceutical University, Laboratory of Drug Metabolism and PharmacokineticsShenyang, China.
[Leng, Ping] The Affiliated Hospital of Qingdao University, Department of PharmacyQingdao, China.
RP Leng, P (reprint author), The Affiliated Hospital of Qingdao University, Department of Pharmacy, Qingdao, China.
EM 18661808926@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610899
EP 1610912
DI 10.3389/pore.2023.1610899
PG 14
ER
PT J
AU Janka, M
Zalatnai, A
AF Janka, Maria
Zalatnai, Attila
TI Correlations between the histopathological alterations in minor salivary glands and the clinically suspected Sjogren’s syndrome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; clinicopathology; retrospective study; Sjogren syndrome; labial gland biopsy
ID immunohistochemistry; clinicopathology; retrospective study; Sjogren syndrome; labial gland biopsy
AB In sicca syndrome patients the xerostomia, xerophthalmia and the serological findings may strongly suggest the autoimmune Sjogren’s syndrome, but the histological findings in the labial salivary gland biopsies do not always justify the suspected diagnosis. The aim of this study was to compare the histomorphological changes and the clinical findings in patients with pathologically established Sjogren’s syndrome and in cases with negative histology. A total of 133 labial biopsies have been retrospectively evaluated from 2015 to May 2022, and the characteristic Sjogren’s lesions were found in 67 cases. According to the clinical data, 34 cases proved to be primary, and 33 were associated (“secondary”) forms. In 66 cases, the histology did not justify Sjogren’s syndrome; a significant acinar loss, fibrolipomatous infiltration, and mild sialadenitis had led to the clinical symptoms. In Sjogren’s histologies, the acinar loss was detected in just 31.8% of cases, which might indicate that the diminished saliva production represents immune-mediated hypofunction rather than direct damage of the acini. This is the first systemic study in Hungary investigating the correlation between pathological alterations and clinical findings.
C1 [Janka, Maria] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Zalatnai, Attila] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Zalatnai, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM zalatnai.attila@med.semmelweis-univ.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610905
EP 1610911
DI 10.3389/pore.2023.1610905
PG 7
ER
PT J
AU Vlahovic, I
Rajc, J
Svagelj, I
Solic, K
Svagelj, D
AF Vlahovic, Ivan
Rajc, Jasmina
Svagelj, Ivan
Solic, Kresimir
Svagelj, Drazen
TI Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; colorectal cancer (CRC); CDX2; dMMR; regression model
ID immunohistochemistry; colorectal cancer (CRC); CDX2; dMMR; regression model
AB CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRCin the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR.Our study showed a significant association betweenCDX2expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/ PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed thatCDX2 expression loss can be used as a predictive factor for dMMR,which should be confirmed by further studies.
C1 [Vlahovic, Ivan] University of Osijek, Faculty of Medicine, Clinical Hospital Center Osijek, Department of Abdominal SurgeryOsijek, Croatia.
[Rajc, Jasmina] University of Osijek, Faculty of Medicine, Clinical Hospital Center Osijek, Department of Pathology and Forensic MedicineOsijek, Croatia.
[Svagelj, Ivan] General County Hospital Vinkovci, Department of Pathology and CytologyVinkovci, Croatia.
[Solic, Kresimir] University of Osijek, Faculty of Medicine, Clinical Hospital Center Osijek, Department of Medical Statistics and Medical InformaticsOsijek, Croatia.
[Svagelj, Drazen] General County Hospital Vinkovci, Department of Pathology and CytologyVinkovci, Croatia.
RP Vlahovic, I (reprint author), University of Osijek, Faculty of Medicine, Clinical Hospital Center Osijek, Department of Abdominal Surgery, Osijek, Croatia.
EM ivan_vlahovic@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610908
EP 1610918
DI 10.3389/pore.2023.1610908
PG 11
ER
PT J
TI Characterization of the input material quality for the production of tisagenlecleucel by multiparameter flow cytometry and its relation to the clinical outcome
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunotherapy; CAR-T cells; tisagenlecleucel; B-cell lymphoma and leukemia; Kymriah
ID immunotherapy; CAR-T cells; tisagenlecleucel; B-cell lymphoma and leukemia; Kymriah
AB Tisagenlecleucel (tisa-cel) is a CD19-specific CAR-T cell product approved for the treatment of relapsed/refractory (r/r) DLBCL or B-ALL. We have followed a group of patients diagnosed with childhood B-ALL (n = 5), adult B-ALL (n = 2), and DLBCL (n = 25) who were treated with tisa-cel under non-clinical trial conditions. The goal was to determine how the intensive pretreatment of patients affects the produced CAR-T cells, their in vivo expansion, and the outcome of the therapy. Multiparametric flow cytometry was used to analyze the material used for manufacturing CAR-T cells (apheresis), the CAR-T cell product itself, and blood samples obtained at three timepoints after administration. We present the analysis of memory phenotype of CD4/ CD8 CAR-T lymphocytes (CD45RA, CD62L, CD27, CD28) and the expression of inhibitory receptors (PD-1, TIGIT). In addition, we show its relation to the patients’ clinical characteristics, such as tumor burden and sensitivity to prior therapies. Patients who responded to therapy had a higher percentage of CD8+CD45RA+CD27+ T cells in the apheresis, although not in the produced CAR-Ts. Patients with primary refractory aggressive B-cell lymphomas had the poorest outcomes which was characterized by undetectable CAR-T cell expansion in vivo. No clear correlation of the outcome with the immunophenotypes of CAR-Ts was observed. Our results suggest that an important parameter predicting therapy efficacy is CAR-Ts’ level of expansion in vivo but not the immunophenotype. After CAR-T cells’ administration, measurements at several timepoints accurately detect their proliferation intensity in vivo. The outcome of CAR-T cell therapy largely depends on biological characteristics of the tumors rather than on the immunophenotype of produced CAR-Ts.
CR Siddiqi T, Abramson JS, Li D, Brown W, Devries T, Dave K, et al. Patient characteristics and pre-infusion biomarkers of inflammation correlate with clinical outcomes after treatment with the defined composition, CD19-targeted CAR T cell product, JCAR017. Blood, 2017, 130:193., DOI 10.1182/blood.V130.Suppl_1.193.193
Zhang X, Yang JF, Li JJ, Li WQ, Song D, Lu XA, et al. Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia. Cancer Immunol Immunother, 2022, 71(3):689–703., DOI 10.1007/s00262-021-03009-z
Martino M, Alati C, Canale FA, Musuraca G, Martinelli G, Cerchione C. A Review of clinical outcomes of CAR T-Cell therapies for B-Acute lymphoblastic leukemia. Int J Mol Sci, 2021, 22:2150., DOI 10.3390/ijms22042150
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med, 2019, 380:45–56., DOI 10.1056/NEJMoa1804980
Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, D’Aveni-Piney M, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/ refractory diffuse large B-cell lymphoma. Blood Adv, 2020, 4(22):5607–15., DOI 10. 1182/bloodadvances.2020003001
Riedell PA, Walling C, Nastoupil LJ, Pennisi M, Maziarz RT, McGuirk JP, et al. A multicenter retrospective analysis of clinical outcomes, toxicities, and patterns of use in institutions utilizing commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed/refractory aggressive B-cell lymphomas. Blood, 2019, 134:1599., DOI 10. 1182/blood-2019-127490
Dean EA, Mhaskar RS, Lu H, Mousa MS, Krivenko GS, Lazaryan A, et al. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv, 2020, 4(14):3268–76., DOI 10. 1182/bloodadvances.2020001900
Monfrini C, Stella F, Aragona V, Magni M, Ljevar S, Vella C, et al. Phenotypic composition of commercial anti-CD19 CAR-T cells affects in vivo expansion and disease response in large B-cell lymphoma patients. Clin Cancer Res, 2022, 28: 3378–86., DOI 10.1158/1078-0432.ccr-22-0164
Cuffel A, Allain V, Faivre L, Di Blasi R, Morin F, Vercellino L, et al. Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma. Blood Adv, 2022, 6:4657–60., DOI 10.1182/bloodadvances.2022007057
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610914
EP 1610925
DI 10.3389/pore.2023.1610914
PG 12
ER
PT J
AU Horesh, A
Pollack, R
Nechushtan, H
Dresner-Pollak, R
Neuman, T
AF Horesh, Adi
Pollack, Rena
Nechushtan, Hovav
Dresner-Pollak, Rivka
Neuman, Tzahi
TI Tumor PD-L1 expression and molecular profiling are not associated with immune checkpoint inhibitor-induced thyroid dysfunction in advanced NSCLC patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE NSCLC; Non-small cell lung cancer; PD-1; programmed cell death 1; PD-L1; programmed cell death ligand 1
ID NSCLC; Non-small cell lung cancer; PD-1; programmed cell death 1; PD-L1; programmed cell death ligand 1
AB Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), however are frequently associated with thyroid immune-related adverse events (IRAEs). We investigated the association between patient characteristics, tumor PDL1 expression and molecular profile with the development of thyroid IRAEs in NSCLC patients. Methods: Single center, retrospective study including 107 NSCLC patients treated with PD-1/PD-L1 inhibitors from April 2016 to July 2020. All patients were euthyroid at baseline with at least two TSH measurements post-treatment initiation. The primary outcome was the difference in tumor PD-L1 expression in patients who developed any thyroid IRAEs versus those who remained euthyroid. Additional outcomes included development of overt thyroid dysfunction, the association of specific molecular alterations with thyroid IRAEs, and onset of thyroid IRAEs as a function of tumor PD-L1 expression. Results: Overall, 37 (34.6%) patients developed any thyroid dysfunction and 18 (16.8%) developed overt thyroid dysfunction. Tumor PD-L1 staining intensity was not associated with thyroid IRAEs. TP53 mutation was less likely to be associated with any thyroid dysfunction (p < 0.05) and no association was found between EGFR, ROS, ALK or KRAS mutations. There was no association between PD-L1 expression and time to develop thyroid IRAEs. Conclusion: PD-L1 expression is not associated with the development of thyroid dysfunction in advanced NSCLC patients treated with ICIs, suggesting that thyroid IRAEs are unrelated to tumor PD-L1 expression.
C1 [Horesh, Adi] Hebrew University of Jerusalem, The Faculty of MedicineJerusalem, Israel.
[Pollack, Rena] Hebrew University of Jerusalem, The Faculty of MedicineJerusalem, Israel.
[Nechushtan, Hovav] Hebrew University of Jerusalem, The Faculty of MedicineJerusalem, Israel.
[Dresner-Pollak, Rivka] Hebrew University of Jerusalem, The Faculty of MedicineJerusalem, Israel.
[Neuman, Tzahi] Hebrew University of Jerusalem, The Faculty of MedicineJerusalem, Israel.
RP Neuman, T (reprint author), Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.
EM tneuman@hadassah.org.il
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610951
EP 1610958
DI 10.3389/pore.2023.1610951
PG 8
ER
PT J
AU Li, Y
Xiong, Ch
Wu, LL
Zhang, YB
Wu, Sh
Chen, FY
Xu, HQ
Liao, FH
AF Li, Yue
Xiong, Chao
Wu, Li Li
Zhang, Yuan Bo
Wu, Sha
Chen, Fen Yu
Xu, Hua Qi
Liao, Fei Hong
TI Tumor subtypes and signature model construction based on chromatin regulators for better prediction of prognosis in uveal melanoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; uveal melanoma; TCGA; chromatin regulators; tumor subtypes
ID prognosis; uveal melanoma; TCGA; chromatin regulators; tumor subtypes
AB Background: Uveal Melanoma (UM) is the most prevalent primary intraocular malignancy in adults. This study assessed the importance of chromatin regulators (CRs) in UM and developed a model to predict UM prognosis. Methods: Gene expression data and clinical information for UM were obtained from public databases. Samples were typed according to the gene expression of CRs associated with UM prognosis. The prognostic key genes were further screened by the protein interaction network, and the risk model was to predict UMprognosis using the least absolute shrinkage and selection operator (LASSO) regression analysis and performed a test of the risk mode. In addition, we performed gene set variation analysis, tumor microenvironment, and tumor immune analysis between subtypes and risk groups to explore the mechanisms influencing the development of UM. Results: We constructed a signature model consisting of three CRs (RUVBL1, SIRT3, and SMARCD3), which was shown to be accurate, and valid for predicting prognostic outcomes in UM. Higher immune cell infiltration in poor prognostic subtypes and risk groups. The Tumor immune analysis and Tumor Immune Dysfunction and Exclusion (TIDE) score provided a basis for clinical immunotherapy in UM. Conclusion: The risk model has prognostic value for UM survival and provides new insights into the treatment of UM.
C1 [Li, Yue] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Xiong, Chao] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Wu, Li Li] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Zhang, Yuan Bo] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Wu, Sha] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Chen, Fen Yu] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Xu, Hua Qi] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
[Liao, Fei Hong] Nanchang University, School of Ophthalmology and OptometryNanchang, Jiangxi, China.
RP Liao, FH (reprint author), Nanchang University, School of Ophthalmology and Optometry, Nanchang, China.
EM lhfzf@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1610980
EP 1610996
DI 10.3389/pore.2023.1610980
PG 17
ER
PT J
AU Huang, H
Li, Z
Xia, Y
Zhao, Z
Wang, D
Jin, H
Liu, F
Yang, Y
Shen, L
Lu, Z
AF Huang, Huizhen
Li, Zhiheng
Xia, Yue
Zhao, Zhenhua
Wang, Dandan
Jin, Hongyan
Liu, Fang
Yang, Ye
Shen, Liyijing
Lu, Zengxin
TI Association between radiomics features of DCE-MRI and CD8+ and CD4+ TILs in advanced gastric cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE radiomics; CD4+; CD8+; advanced gastric cancer (AGC); dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
ID radiomics; CD4+; CD8+; advanced gastric cancer (AGC); dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
AB Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer. Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density. Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630–0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = −0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = −0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856). Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.
C1 [Huang, Huizhen] Shaoxing University School of MedicineShaoxing, China.
[Li, Zhiheng] Anhui Provincial Hospital, Department of RadiologyHefei, China.
[Xia, Yue] Shaoxing University School of MedicineShaoxing, China.
[Zhao, Zhenhua] Shaoxing People’s Hospital, Department of RadiologyShaoxing, China.
[Wang, Dandan] Shaoxing People’s Hospital, Department of RadiologyShaoxing, China.
[Jin, Hongyan] Shaoxing People’s Hospital, Country Department of PathologyShaoxing, China.
[Liu, Fang] Shaoxing People’s Hospital, Country Department of PathologyShaoxing, China.
[Yang, Ye] Shaoxing People’s Hospital, Country Department of PathologyShaoxing, China.
[Shen, Liyijing] Shaoxing People’s Hospital, Department of RadiologyShaoxing, China.
[Lu, Zengxin] Shaoxing People’s Hospital, Department of RadiologyShaoxing, China.
RP Lu, Z (reprint author), Shaoxing People’s Hospital, Department of Radiology, Shaoxing, China.
EM luzx777@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611001
EP 1611011
DI 10.3389/pore.2023.1611001
PG 11
ER
PT J
AU Zhao, B
Wang, J
Ma, Z
Ye, H
Yang, T
Meng, K
AF Zhao, Bochao
Wang, Jingchao
Ma, Zhicheng
Ye, Haikun
Yang, Tao
Meng, Kewei
TI Development and validation of a prognostic nomogram for rectal cancer patients who underwent surgical resection
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; prognostic; nomogram; SEER; rectal cancer
ID survival; prognostic; nomogram; SEER; rectal cancer
AB Objective: The purpose of this study was to develop and validate a nomogram model for the prediction of survival outcome in rectal cancer patients who underwent surgical resection. Methods: A total of 9,919 consecutive patients were retrospectively identified using the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were determined by the univariate and multivariate Cox analysis. The nomogram model for the prediction of cancer-specific survival (CSS) in rectal cancer patients were developed based on these prognostic variables, and its predictive power was assessed by the concordance index (C-index). Calibration curves were plotted to evaluate the associations between predicted probabilities and actual observations. The internal and external cohort were used to further validate the predictive performance of the prognostic nomogram. Results: All patients from the SEER database were randomly split into a training cohort (n = 6,944) and an internal validation cohort (n = 2,975). The baseline characteristics of two cohorts was comparable. Independent prognostic factors were identified as age, pT stage, lymph node metastasis, serum CEA level, tumor size, differentiation type, perineural invasion, circumferential resection margin involvement and inadequate lymph node yield. In the training cohort, the C-index of the nomogram was 0.719 (95% CI: 0.696–0.742), which was significantly higher than that of the TNM staging system (C-index: 0.606, 95% CI: 0.583–0.629). The nomogram had a C-index of 0.726 (95% CI: 0.691–0.761) for the internal validation cohort, indicating a good predictive power. In addition, an independent cohort composed of 202 rectal cancer patients from our institution were enrolled as the external validation. Compared with the TNM staging system (C-index: 0.573, 95% CI: 0.492–0.654), the prognostic nomogram still showed a better predictive performance, with the C-index of 0.704 (95% CI: 0.626–0.782). Calibration plots showed a good consistency between predicted probability and the actual observation in the training and two validation cohorts. Conclusion: The nomogram showed an excellent predictive ability for survival outcome of rectal cancer patients, and it might provide an accurate prognostic stratification and help clinicians determine individualized treatment strategies.
C1 [Zhao, Bochao] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
[Wang, Jingchao] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
[Ma, Zhicheng] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
[Ye, Haikun] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
[Yang, Tao] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
[Meng, Kewei] Tianjin First Central Hospital, Department of Gastrointestinal SurgeryTianjin, China.
RP Meng, K (reprint author), Tianjin First Central Hospital, Department of Gastrointestinal Surgery, Tianjin, China.
EM doctormkw1969@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611014
EP 1611023
DI 10.3389/pore.2023.1611014
PG 10
ER
PT J
AU Seftor, R
Seftor, E
Hendrix, M
AF Seftor, E. B. Richard
Seftor, A. Elisabeth
Hendrix, J. C. Mary
TI CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE TRAP1; vasculogenic mimicry; CVM-1118; foslinanib; Hsp75; STK11; NF2
ID TRAP1; vasculogenic mimicry; CVM-1118; foslinanib; Hsp75; STK11; NF2
AB CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2- phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.
C1 [Seftor, E. B. Richard] Shepherd University, Department of BiologyShepherdstown, WV, USA.
[Seftor, A. Elisabeth] Shepherd University, Department of BiologyShepherdstown, WV, USA.
[Hendrix, J. C. Mary] Shepherd University, Department of BiologyShepherdstown, WV, USA.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611038
EP 1611054
DI 10.3389/pore.2023.1611038
PG 17
ER
PT J
AU He, X
Zhou, S
Li, H
Gou, Y
Jia, D
AF He, Xiaohong
Zhou, Sicheng
Li, Hongjun
Gou, Yue
Jia, Dan
TI Prognostic role of pretreatment skeletal muscle index in gastric cancer patients: A meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE meta-analysis; prognosis; gastric cancer; pretreatment; skeletal muscle index
ID meta-analysis; prognosis; gastric cancer; pretreatment; skeletal muscle index
AB Background: The association between pretreatment skeletal muscle index (SMI) and long-term survival of gastric cancer patients remains unclear up to now. The aim of this meta-analysis was to identify the prognostic value of pretreatment SMI in gastric cancer. Methods: The PubMed, EMBASE and Web of Science electronic databases were searched up to 5 June 2022 for relevant studies. The primary outcome was overall survival (OS) and the second outcomes were disease-free survival (DFS) and cancer-specific survival (CSS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and survival of gastric cancer patients. All statistical analyses were conducted by STATA 15.0 software. Results: A total of 31 retrospective studies involving 12,434 patients were enrolled in this meta-analysis. The pooled results demonstrated that lower pretreatment was significantly associated with poorer OS (HR = 1.53, p < 0.001). Besides, lower pretreatment SMI was also related with worse DFS (HR = 1.39, p < 0.001) and CSS (HR = 1.96, p < 0.001). Conclusion: Pretreatment SMI was significantly associated with prognosis of gastric cancer patients and lower SMI predicted worse survival. However, more prospective high-quality studies are still needed to verify our findings.
C1 [He, Xiaohong] Sichuan University, West China Hospital, Cancer CenterChengdu, China.
[Zhou, Sicheng] Sichuan University / West China School of Nusing Sichuan University, West China Hospital, Outpatient DepartmentChengdu, China.
[Li, Hongjun] Sichuan University / West China School of Nusing Sichuan University, West China Hospital, Outpatient DepartmentChengdu, China.
[Gou, Yue] Sichuan University / West China School of Nusing Sichuan University, West China Hospital, Outpatient DepartmentChengdu, China.
[Jia, Dan] Sichuan University / West China School of Nusing Sichuan University, West China Hospital, Outpatient DepartmentChengdu, China.
RP Jia, D (reprint author), Sichuan University / West China School of Nusing Sichuan University, West China Hospital, Outpatient Department, Chengdu, China.
EM 417522774@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611055
EP 1611064
DI 10.3389/pore.2023.1611055
PG 10
ER
PT J
AU Zhu, J
Zhu, X
Xie, F
Ding, Y
Lu, H
Dong, Y
Li, P
Fu, J
Liang, A
Zeng, Y
Xiu, B
AF Zhu, Jingjing
Zhu, Xinyu
Xie, Fengyang
Ding, Yi
Lu, Huina
Dong, Yan
Li, Ping
Fu, Jianfei
Liang, Aibin
Zeng, Yu
Xiu, Bing
TI Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenstrom macroglobulinemia during treatment with BTK inhibitors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE resistance; Waldenstrom macroglobulinemia; circulating tumor DNA (ctDNA); BTK inhibitor; ascites
ID resistance; Waldenstrom macroglobulinemia; circulating tumor DNA (ctDNA); BTK inhibitor; ascites
AB Background: Waldenstrom macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton’s tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression. Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse. Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy.
C1 [Zhu, Jingjing] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Zhu, Xinyu] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Xie, Fengyang] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Ding, Yi] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Lu, Huina] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Dong, Yan] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Li, Ping] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Fu, Jianfei] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Liang, Aibin] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
[Zeng, Yu] Tongji University School of Medicine, Tongji Hospital, Department of PathologyShanghai, China.
[Xiu, Bing] Tongji University School of Medicine, Tongji Hospital, Department of HematologyShanghai, China.
RP Xiu, B (reprint author), Tongji University School of Medicine, Tongji Hospital, Department of Hematology, Shanghai, China.
EM xiubing1233@tongji.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611070
EP 1611078
DI 10.3389/pore.2023.1611070
PG 9
ER
PT J
AU Revesz, J
Posfai, B
Pajor, L
Papdan, T
Varga, L
Paczona, V
Varga, Z
Sukosd, F
Maraz, A
AF Revesz, Janos
Posfai, Boglarka
Pajor, Laszlo
Papdan, Timea
Varga, Linda
Paczona, R. Viktor
Varga, Zoltan
Sukosd, Farkas
Maraz, Aniko
TI Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE urinary bladder cancer; fibroblast growth factor receptor; FGFR mutation; programmed death-ligand 1 expression; combined positive score
ID urinary bladder cancer; fibroblast growth factor receptor; FGFR mutation; programmed death-ligand 1 expression; combined positive score
AB Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival. Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary. FGFR3 mutations from the most infiltrative areas of the tumor were analyzed by targeted next-generation sequencing and PD-L1 (28-8 DAKO) tests (tumor positive score -TPS and combined positives score–CPS). In T0 cases FGFR3 mutations were analyzed from the earlier resection samples. Survival and oncological treatment data were collected from the National Health Insurance Fund (NHIF). Neoadjuvant, adjuvant and palliative conventional chemotherapies were allowed; immunotherapies were not. The relationship between the covariates was tested using chi-square tests, and survival analysis was performed using the Kaplan-Meier model and Cox proportional hazards regression. Results: PD-L1 and FGFR could be tested successfully in 215 of the 310 UBC samples [pT0cyst 19 (8.8%); St.0-I 43 (20%); St.II 41 (19%); St.III-IV 112 (52%)]. Significant pairwise dependency was found between tumor stage, FGFR3 mutation status and PD-L1 expression (p < 0.01). Samples with FGFR mutation were more common in less advanced stages and were also less likely to demonstrate PD-L1 expression. The effect of all investigated factors on survival was found to correlate with tumor stage. Conclusion: FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.
C1 [Revesz, Janos] Szegedi Tudomanyegyem, Doktori IskolaSzeged, Hungary.
[Posfai, Boglarka] University of Szeged, Department of OncotherapySzeged, Hungary.
[Pajor, Laszlo] University of Szeged, Department of UrologySzeged, Hungary.
[Papdan, Timea] University of Szeged, Department of OncotherapySzeged, Hungary.
[Varga, Linda] University of Szeged, Department of OncotherapySzeged, Hungary.
[Paczona, R. Viktor] University of Szeged, Department of OncotherapySzeged, Hungary.
[Varga, Zoltan] University of Szeged, Department of OncotherapySzeged, Hungary.
[Sukosd, Farkas] University of Szeged, Department of PathologySzeged, Hungary.
[Maraz, Aniko] University of Szeged, Department of OncotherapySzeged, Hungary.
RP Maraz, A (reprint author), University of Szeged, Department of Oncotherapy, Szeged, Hungary.
EM dr.aniko.maraz@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611077
EP 1611088
DI 10.3389/pore.2023.1611077
PG 12
ER
PT J
AU Li, H
Yang, Ch
Chen, K
Sun, M
AF Li, Hui
Yang, Chenbo
Chen, Kuisheng
Sun, Miaomiao
TI Expression significance of Emi1, UBCH10 and CyclinB1 in esophageal squamous cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor proliferation; Emi1; UBCH10; CyclinB1; tumor apoptosis
ID tumor proliferation; Emi1; UBCH10; CyclinB1; tumor apoptosis
AB Despite significant advances in the diagnosis and treatment of esophageal squamous cell carcinoma (ESCC), esophageal cancer is still a heavy social and medical burden due to its high incidence. Uncontrolled division and proliferation is one of the characteristics of tumor cells, which will promote rapid tumor growth and metastasis. Early mitotic inhibitor 1 (Emi1), ubiquitinconjugating enzyme 10 (UBCH10) and CyclinB1 are important proteins involved in the regulation of cell cycle. In this study, the expression of Emi1, UBCH10 and CyclinB1 in ESCC tissues and adjacent normal tissues will be analyzed by immunohistochemistry and in-situ hybridization techniques, and their relationship with tumor proliferation and apoptosis will be analyzed. The results showed that Emi1, UBCH10 and CyclinB1 genes and proteins were highly expressed in tumor tissues, which were correlated with tumor grade, lymph node metastasis and pathological stage, and positively correlated with tumor proliferation. Emi1, UBCH10 and CyclinB1 are also positively correlated. It is speculated that Emi1, UBCH10 and CyclinB1 genes synergically promote tumor proliferation and inhibit apoptosis, which may be potential diagnostic and therapeutic targets for ESCC.
C1 [Li, Hui] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Yang, Chenbo] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Chen, Kuisheng] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
[Sun, Miaomiao] The First Affiliated Hospital of Zhengzhou University, Department of PathologyZhengzhou, China.
RP Sun, M (reprint author), The First Affiliated Hospital of Zhengzhou University, Department of Pathology, Zhengzhou, China.
EM sunmiaomiaohd@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611081
EP 1611092
DI 10.3389/pore.2023.1611081
PG 12
ER
PT J
AU Long, J
Cong, F
Wei, Y
Liu, J
Tang, W
AF Long, Junxian
Cong, Fengyun
Wei, Yousheng
Liu, Jungang
Tang, Weizhong
TI Increased Kremen2 predicts worse prognosis in colon cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colon cancer; prognosis; bioinformatic; Kremen2; tumour infiltrating cells
ID colon cancer; prognosis; bioinformatic; Kremen2; tumour infiltrating cells
AB Background: Colon cancer (CC) is the fifth most prevalent cancer around the globe and poses a major risk to human health. Even though Kremen2 serves as a prognostic indicator in individuals with malignant tumours, its role in evaluating the prognosis of individuals with colon cancer has not been confirmed. Methods: Here, we examined the protein expression of Kremen2 in CC tissues and paired adjacent normal tissues by immunohistochemistry (IHC), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Kremen2 levels and CC. In addition, the associations between Kremen2 mRNA expression and infiltrating immune cells were examined. Results: The study showed that the mRNA expression and protein level of Kremen2 were increased in CC tissues compared with adjacent normal tissues. According to Kaplan–Meier analysis, high Kremen2 expression in CC was linked to poor overall survival and progression-free survival. Clinical correlation analysis highlighted that a high level of Kremen2 expression was strongly linked with tumour progression, particularly lymph node metastasis. Cox regression analysis highlighted that Kremen2 was an independent prognostic indicator for CC. Bioinformatic studies highlighted that Kremen2 might be associated with the immune status in CC. Conclusion: Increased Kremen2 could serve as a potential prognostic CC biomarker.
C1 [Long, Junxian] Guangxi Medical University Cancer Hospital, Department of Gastrointestinal SurgeryNanning, Guangxi, China.
[Cong, Fengyun] Guangxi Medical University Cancer Hospital, Department of Gastrointestinal SurgeryNanning, Guangxi, China.
[Wei, Yousheng] Guangxi Medical University Cancer Hospital, Department of Gynecologic OncologyNanning, Guangxi, China.
[Liu, Jungang] Guangxi Medical University Cancer Hospital, Department of Gastrointestinal SurgeryNanning, Guangxi, China.
[Tang, Weizhong] Guangxi Medical University Cancer Hospital, Department of Gastrointestinal SurgeryNanning, Guangxi, China.
RP Tang, W (reprint author), Guangxi Medical University Cancer Hospital, Department of Gastrointestinal Surgery, Nanning, China.
EM tangweizhong@gxmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611082
EP 1611092
DI 10.3389/pore.2023.1611082
PG 11
ER
PT J
TI Potential predictors of immunotherapy in small cell lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE tumor microenvironment; PD-L1 expression; small cell lung cancer; mutational burden; molecular subtyping
ID tumor microenvironment; PD-L1 expression; small cell lung cancer; mutational burden; molecular subtyping
AB Lung cancer is one of the leading causes of cancer-related deaths worldwide, with small cell lung cancer (SCLC) having the worst prognosis. SCLC is diagnosed late in the disease’s progression, limiting treatment options. The most common treatment for SCLC is chemotherapy. As the disease progresses, immunotherapy, most commonly checkpoint inhibitor medication, becomes more important. Efforts should be made in the development of immunotherapy to map specific biomarkers, which play a role in properly assigning a type of immunotherapy to the right cohort of patients, where the benefits outweigh any risks or adverse effects. The objective of this review was to provide a thorough assessment of current knowledge about the nature of the tumor process and treatment options for small cell lung cancer, with a focus on predictive biomarkers. According to the information obtained, the greatest potential, which has already been directly demonstrated in some studies, has characteristics such as tumor microenvironment composition, tumor mutation burden, and molecular subtyping of SCLC. Several other aspects appear to be promising, but more research, particularly prospective studies on a larger number of probands, is required. However, it is clear that this field of study will continue to expand, as developing a reliable method to predict immunotherapy response is a very appealing goal of current medicine and research in the field of targeted cancer therapy.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611086
EP 1611097
DI 10.3389/pore.2023.1611086
PG 12
ER
PT J
AU Zuo, X
Wu, W
Shi, P
Liu, T
Yu, N
Li, L
AF Zuo, Xuan
Wu, L. Wei
Shi, Peng
Liu, M. Tian
Yu, Na
Li, Lei
TI A case report of recurrent leiomyosarcoma with chondrosarcoma differentiation in the abdominal wall and a review of the literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE recurrence; case report; leiomyosarcoma; heterologous differentiation; chondrosarcoma
ID recurrence; case report; leiomyosarcoma; heterologous differentiation; chondrosarcoma
AB Leiomyosarcoma with heterologous differentiation is relatively rare. To date, only 19 cases have been reported in the English literature. Heterologous components frequently show histological pleomorphism, while those exhibiting well-differentiated morphology are seldom reported. Here, we report a 34-year-old female diagnosed with leiomyosarcoma and developed abdominal wall recurrence 8 years after primary surgery. The recurrent tumor mainly comprised well-differentiated chondrosarcoma except a single focus of leiomyosarcoma. Due to the rarity and prolonged onset of such a transition, our case provides insight into the understanding of this phenomenon.
C1 [Zuo, Xuan] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
[Wu, L. Wei] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
[Shi, Peng] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
[Liu, M. Tian] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
[Yu, Na] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
[Li, Lei] Sichuan University, West China Second University Hospital, Department of PathologyChengdu, China.
RP Li, L (reprint author), Sichuan University, West China Second University Hospital, Department of Pathology, Chengdu, China.
EM lipath@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611109
EP 1611113
DI 10.3389/pore.2023.1611109
PG 5
ER
PT J
AU Fan, B
Zheng, X
Wang, Y
Hu, X
AF Fan, Bohan
Zheng, Xin
Wang, Yicun
Hu, Xiaopeng
TI Predicting prognosis and clinical efficacy of immune checkpoint blockade therapy via interferon-alpha response in muscle-invasive bladder cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE muscle-invasive bladder cancer; immune checkpoint blockade therapy; interferonalpha response; tumor microenvironment; prognostic biomarkers
ID muscle-invasive bladder cancer; immune checkpoint blockade therapy; interferonalpha response; tumor microenvironment; prognostic biomarkers
AB Background: Immune checkpoint blockade (ICB) can prompt durable and robust responses in multiple cancers, involving muscle-invasive bladder cancer (MIBC). However, only a limited fraction of patients received clinical benefit. Clarifying the determinants of response and exploring corresponding predictive biomarkers is key to improving outcomes. Methods: Four independent formerly published cohorts consisting of 641 MIBC patients were enrolled in this study. We first analyzed the associations between various cancer hallmarks and ICB therapy response in two immunotherapeutic cohorts to identify the leading prognostic hallmark in MIBC. Furthermore, advanced machine learning methods were performed to select robust and promising predictors from genes functioning in the above leading pathway. The predictive ability of selected genes was also validated in multiple MIBC cohorts. Results: We identified and verified IFNα response as the leading cancer hallmark indicating better treatment responses, favorable overall survival, and an inflamed tumor microenvironment with higher infiltration of immune effector cells in MIBC patients treated with ICB therapy. Subsequently, two commonly selected genes, CXCL10 and LAMP3, implied better therapy response and the CXCL10highLAMP3high patients would benefit more from ICB therapy, which was comprehensively validated from the perspective of gene expression, clinical response, patient survival and immune features. Conclusion: Higher IFNα response primarily predicted better ICB therapeutic responses and reflected an inflamed microenvironment in MIBC. A composite of CXCL10 and LAMP3 expression could serve as promising predictive biomarkers for ICB therapeutic responses and be beneficial for clinical decision-making in MIBC.
C1 [Fan, Bohan] Capital Medical University, Beijing Chao-Yang Hospital, Department of UrologyBeijing, China.
[Zheng, Xin] Northwestern University, Feinberg School of Medicine, Comprehensive Transplant CenterChicago, IL, USA.
[Wang, Yicun] Capital Medical University, Beijing Chao-Yang Hospital, Department of UrologyBeijing, China.
[Hu, Xiaopeng] Capital Medical University, Beijing Chao-Yang Hospital, Department of UrologyBeijing, China.
RP Hu, X (reprint author), Capital Medical University, Beijing Chao-Yang Hospital, Department of Urology, Beijing, China.
EM xiaopeng_hu@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611117
EP 1611127
DI 10.3389/pore.2023.1611117
PG 11
ER
PT J
AU Revesz, M
Oberna, F
Slezak, A
Ferenczi,
Kenessey, I
Takacsi-Nagy, Z
AF Revesz, Monika
Oberna, Ferenc
Slezak, Andras
Ferenczi, Ors
Kenessey, Istvan
Takacsi-Nagy, Zoltan
TI The characteristics of head and neck squamous cell cancer in young adults: A retrospective single-center study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; risk factors; prognostic factors; head and neck cancer; young adults
ID survival; risk factors; prognostic factors; head and neck cancer; young adults
AB We aimed to characterize clinical and prognostical factors of primary head and neck squamous cell carcinoma (HNSCC) in 85 young patients (≤39 years, median age: 37 years; between 2000–2018) in comparison with 140 institutional general HNSCC patients (median age: 61.5 years). The patient’s medical records were collected from the institutional database. The prevalence of smoking and alcohol consumption (65.8% and 48.1%) in the young group exceeded the regional population average but was below the institutional (86.4% and 55%) general HNSCC patient population. Primary tumor sites in the group of young patients were as follows: oral cavity (56.4%), oropharynx (17.6%), hypopharynx (11.7%), and larynx (14.1%). Cumulative fiveyear overall survival was 44.2% in the young group, but significantly better with early T (T1-2 vs. T3-4: 52.6% vs. 26.7%; p = 0.0058) and N0 status (N0 vs. N+: 65.2% vs. 32.3%; p = 0.0013). Young age, abstinence, earlier stage and laryngeal tumor site might predict a better prognosis. The age distribution and the high prevalence of traditional risk factors among the young patients as well as the predominance of oral cavity tumor localization suggest that the early onset of tumor development could be originated from the premature failure of the intrinsic protective mechanisms.
C1 [Revesz, Monika] National Institute of Oncology, Multidisciplinary Center of Head and Neck OncologyBudapest, Hungary.
[Oberna, Ferenc] National Institute of Oncology, Multidisciplinary Center of Head and Neck OncologyBudapest, Hungary.
[Slezak, Andras] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Ferenczi, Ors] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
[Kenessey, Istvan] National Institute of Oncology, National Cancer RegistryBudapest, Hungary.
[Takacsi-Nagy, Zoltan] National Institute of Oncology, Center of RadiotherapyBudapest, Hungary.
RP Takacsi-Nagy, Z (reprint author), National Institute of Oncology, Center of Radiotherapy, Budapest, Hungary.
EM takacsi.zoltan@oncol.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611123
EP 1611130
DI 10.3389/pore.2023.1611123
PG 8
ER
PT J
AU Khonrak, Th
Watcharadetwittaya, S
Chamgramol, Y
Intarawichian, P
Deenonpoe, R
AF Khonrak, Thitima
Watcharadetwittaya, Sasithorn
Chamgramol, Yaovalux
Intarawichian, Piyapharom
Deenonpoe, Raksawan
TI RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE papillary thyroid carcinoma; RET rearrangements; CCDC6::RET rearrangement; NCOA4::RET rearrangement; gene rearrangements
ID papillary thyroid carcinoma; RET rearrangements; CCDC6::RET rearrangement; NCOA4::RET rearrangement; gene rearrangements
AB Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The RET gene rearrangements CCDC6::RET and NCOA4::RET are the most common RET gene rearrangements in PTC patients. Different RET::PTC rearrangements are associated with different PTC phenotypes. Methods: Eighty-three formalin-fixed paraffin-embedded (FFPE) PTC samples were examined. The prevalence and expression levels of CCDC6::RET and NCOA4::RET were determined using semi-quantitative polymerase chain reaction (qRT-PCR). The association of these rearrangements with clinicopathological data was investigated. Results: The presence of CCDC6::RET rearrangement was significantly associated with the classic subtype and absence of angio/lymphatic invasion (p < 0.05). While NCOA4::RET was associated with the tall-cell subtype, and presence of angio/ lymphatic invasion and lymph node metastasis (p < 0.05). Multivariate analysis demonstrated that an absence of extrathyroidal extension and extranodal extension were independent predictive factors for CCDC6::RET, whereas the tall-cell subtype, large tumor size, angioinvasion, lymphatic invasion and perineural invasion were independent predictive factors for NCOA4::RET (p < 0.05). However, the mRNA expression level of CCDC6::RET and of NCOA4:: RET were not significantly associated with clinicopathological data. Conclusion: CCDC6::RET was correlated with an innocent PTC subtype and characteristics, but NCOA4::RET correlated with an aggressive phenotype of PTC. Therefore, these RET rearrangements strongly associated with clinicopathological phenotypes and can be used as predictive markers in PTC patients.
C1 [Khonrak, Thitima] Khon Kaen University, Faculty of Medicine, Department of PathologyKhon Kaen, Thailand.
[Watcharadetwittaya, Sasithorn] Khon Kaen University, Faculty of Medicine, Department of PathologyKhon Kaen, Thailand.
[Chamgramol, Yaovalux] Khon Kaen University, Faculty of Medicine, Department of PathologyKhon Kaen, Thailand.
[Intarawichian, Piyapharom] Khon Kaen University, Faculty of Medicine, Department of PathologyKhon Kaen, Thailand.
[Deenonpoe, Raksawan] Khon Kaen University, Faculty of Medicine, Department of PathologyKhon Kaen, Thailand.
RP Deenonpoe, R (reprint author), Khon Kaen University, Faculty of Medicine, Department of Pathology, Khon Kaen, Thailand.
EM raksde@kku.ac.th
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Fugazzola L, Pilotti S, Pinchera A, Vorontsova TV, Mondellini P, Bongarzone I, et al. Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the chernobyl nuclear accident. Cancer Res, 1995, 55(23):5617–20.
Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, et al. Overview of the 2022 WHO classification of thyroid neoplasms. Endocr Pathol, 2022, 33(1):27–63., DOI 10.1007/s12022-022-09707-3
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611138
EP 1611150
DI 10.3389/pore.2023.1611138
PG 13
ER
PT J
AU Han, W
Wang, B
Yong, X
Zhang, Y
Shao, M
Wang, Ch
AF Han, Wen
Wang, Bei
Yong, Xiang
Zhang, Yi
Shao, Mingyu
Wang, Chun
TI Indolent T-lymphoblastic proliferation with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma: a case report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE differential diagnosis; indolent T-lymphoblastic proliferation; iT-LBP; fibrolamellar hepatocellular carcinoma; T-lymphoblastic lymphoma
ID differential diagnosis; indolent T-lymphoblastic proliferation; iT-LBP; fibrolamellar hepatocellular carcinoma; T-lymphoblastic lymphoma
AB Objective: Indolent T-lymphoblastic proliferation (iT-LBP) is a non-neoplastic disease with an indolent clinical course, manifesting as hyperplasia of immature extrathymic T-lymphoblastic cells. Isolated iT-LBP has been observed, but the majority of iT-LBP cases has been seen in conjunction with other diseases. iTLBP is easily misdiagnosed as T-lymphoblastic lymphoma/leukemia, and understanding the disease of indolent T-lymphoblastic proliferation may prevent misdiagnosis and missed diagnosis in pathological diagnosis. Case presentation: We report a case morphology, immunophenotypic, and molecular features of iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma and review relevant literature. Conclusion: iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma is relatively rare and should always be considered as a differential diagnosis of T-lymphoblastic lymphoma and scirrhous hepatocellular carcinoma as the two disorders show highly similar clinical features.
C1 [Han, Wen] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of PathologyUrumqi, China.
[Wang, Bei] People’s Hospital of Xinjiang Uygur Autonomous Region, Graduate Education DepartmentUrumqi, China.
[Yong, Xiang] Anhui Wanbei Coal-Electricity Group General Hospital, Department of PathologySuzhou, China.
[Zhang, Yi] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of PathologyUrumqi, China.
[Shao, Mingyu] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of PathologyUrumqi, China.
[Wang, Chun] People’s Hospital of Xinjiang Uygur Autonomous Region, Department of PathologyUrumqi, China.
RP Wang, Ch (reprint author), People’s Hospital of Xinjiang Uygur Autonomous Region, Department of Pathology, Urumqi, China.
EM hanwen-2@126.com
CR Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health organization classification of haematolymphoid tumours: Lymphoid neoplasms. Leukemia, 2022, 36(7): 1720–48., DOI 10.1038/s41375-022-01620-2
Yang F, Liu T, Zhao H, Hu Z, Xiao L, Liu Y, et al. Indolent T-lymphblastic proliferation: report of a case involving the upper aerodigestive tract. Int J Clin Exp Pathol, 2014, 7(9):6350–6.
Ohgami RS, Zhao S, Ohgami JK, Leavitt MO, Zehnder JL, West RB, et al. TdT+ T-lymphoblastic populations are increased in Castleman disease, in Castleman disease in association with follicular dendritic cell tumors, and in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol, 2012, 36(11):1619–28., DOI 10.1097/PAS.0b013e318264e223
Strauchen JA. Indolent T-lymphoblastic proliferation: Report of a case with an 11-year history and association with myasthenia gravis. Am J Surg Pathol, 2001, 25(3):411–5., DOI 10.1097/00000478-200103000-00018
Wang ZM, Xiao WB, Zheng SS, Sun K, Wang LJ. Hepatocellular carcinoma with indolent T-lymphoblastic proliferation. Leuk Lymphoma, 2006, 47(11): 2424–6., DOI 10.1080/10428190600822151
Woo CG, Huh J. TdT+ T-lymphoblastic proliferation in castleman disease. J Pathol Transl Med, 2015, 49(1):1–4., DOI 10.4132/jptm.2014.11.17
Karki NR, Arfa AS, Savage N, Kutlar A. Indolent T-lymphoblastic proliferation in idiopathic multicentric castleman disease. Acta Haematol, 2022, 145(2):214–20., DOI 10.1159/000520240
Yasuda H, TsutsuiM, Ota Y, Tanaka M, Komatsu N. Indolent T-lymphoblastic proliferation concomitant with acinic cell carcinoma mimicking T-lymphoblastic lymphoma: Case report and literature review. Histopathology, 2018, 72(5):862–6., DOI 10.1111/his.13433
Meyers RL. Tumors of the liver in children. Surg Oncol, 2007, 16(3):195–203., DOI 10.1016/j.suronc.2007.07.002
Samdanci ET, Akatli AN, Soylu NK. Clinicopathological features of two extremely rare hepatocellular carcinoma variants: A brief review of fibrolamellar and scirrhous hepatocellular carcinoma. J Gastrointest Cancer, 2020, 51(4): 1187–92., DOI 10.1007/s12029-020-00500-1
Kakar S, Burgart LJ, Batts KP, Garcia J, Jain D, Ferrell LD. Clinicopathologic features and survival in fibrolamellar carcinoma: Comparison with conventional hepatocellular carcinoma with and without cirrhosis. Mod Pathol, 2005, 18(11): 1417–23., DOI 10.1038/modpathol.3800449
Lalazar G, Simon SM. Fibrolamellar carcinoma: Recent advances and unresolved questions on the molecular mechanisms. Semin Liver Dis, 2018, 38(1):51–9., DOI 10.1055/s-0037-1621710
Eun S, Jeon YK, Jang JJ. Hepatocellular carcinoma with immature T-cell, T-lymphoblastic, proliferation. J Korean Med Sci, 2010, 25(2):309–12., DOI 10. 3346/jkms.2010.25.2.309
Ohgami RS, Arber DA, Zehnder JL, Natkunam Y, Warnke RA. Indolent T-lymphoblastic proliferation, iT-LBP): A review of clinical and pathologic features and distinction from malignant T-lymphoblastic lymphoma. Adv Anat Pathol, 2013, 20(3):137–40., DOI 10.1097/PAP.0b013e31828d17ec
Kong M,Wang Z, Teng X, Xu L, Liu J, Jiang C, et al. Hepatic carcinoma with indolent T-lymphoblastic proliferation, iT-LBP). Int J Clin Exp Pathol, 2018, 11(3): 1674–8.
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611151
EP 1611156
DI 10.3389/pore.2023.1611151
PG 6
ER
PT J
AU Korpas, LK
Beke, L
Varga, D
Bidiga, L
Mehes, G
Molnar, S
AF Korpas, Levente Kristof
Beke, Livia
Varga, Daniel
Bidiga, Laszlo
Mehes, Gabor
Molnar, Sarolta
TI Grade Group accuracy is improved by extensive prostate biopsy sampling, but unrelated to prostatectomy specimen sampling or use of immunohistochemistry
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prostate cancer; needle biopsy; prostatectomy; grade group; pathology
ID prostate cancer; needle biopsy; prostatectomy; grade group; pathology
AB Assessing the accurate Grade Group of a prostate needle biopsy specimen is essential for choosing the adequate therapeutic modality for prostate cancer patients. However, it is well-known that biopsy Grade Group tends to up- or downgrade significantly at radical prostatectomy. We aimed to investigate the correlation between accuracy and biopsy core number, performed immunohistochemical staining (IHC) or prostatectomy specimen sampling, with the latest also being correlated with higher detection rates of adverse pathological features, e.g., positive surgical margins, higher pathological stage or presence of perineural invasion (PnI status). The study cohort consisted of 315 consecutive patients diagnosed with prostate adenocarcinoma via transrectal ultrasound-guided needle biopsy who later underwent radical prostatectomy. We grouped and compared patients based on Grade Group accuracy, presence of IHC on biopsy, margin status, pathological stage, and PnI status. Inter-observer reproducibility was also calculated. Statistical analyzes included ANOVA, Tukey’s multiple comparisons post hoc test, Chi-squared test, and Fleiss kappa statistics. Undergraded cases harboured a significantly lower number of biopsy cores (p < 0.05), than accurately graded cases. Using IHC did not affect grading accuracy significantly, nor did the number of slides from prostatectomy specimens. The mean number of slides was virtually identical when margin status, pathological stage and PnI status of prostatectomy specimens were compared. Inter-observer reproducibility at our institute was calculated as fair (overall kappa = 0.29). Grade Group accuracy is significantly improved by obtaining more cores at biopsy but is unrelated to performed IHC. The extent of sampling prostatectomy specimens, however, did not affect accuracy and failed to significantly improve detection of adverse pathological features.
C1 [Korpas, Levente Kristof] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Beke, Livia] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Varga, Daniel] University of Debrecen, Medical and Health Science Center, Department of UrologyDebrecen, Hungary.
[Bidiga, Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Molnar, Sarolta] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
RP Molnar, S (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, Debrecen, Hungary.
EM molnar.sarolta@med.unideb.hu
CR Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3):209–49., DOI 10.3322/caac.21660
Brawley S, Mohan R, Nein CD. Localized prostate cancer: Treatment options. Am Fam Physician, 2018, 97(12):798–805.
Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. The 2014 international society of urological pathology, ISUP, consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. Am J Surg Pathol, 2016, 40(2):244–52., DOI 10. 1097/PAS.0000000000000530
Penney KL, Stampfer MJ, Jahn JL, Sinnott JA, Flavin R, Rider JR, et al. Gleason grade progression is uncommon. Cancer Res, 2013, 73(16):5163–8., DOI 10.1158/ 0008-5472.CAN-13-0427
Freedland SJ, Kane CJ, Amling CL, Aronson WJ, Presti JC, Terris MK, et al. Delay of radical prostatectomy and risk of biochemical progression inmen with low risk prostate cancer. J Urol, 2006, 175(4):1298–302., DOI 10.1016/S0022-5347(05, 00646-4
Sampurno F, Earnest A, Millar J, Frydenberg M, Murphy D, Delprado W, et al. Population-based study of grade progression in patients who harboured Gleason 3 + 3. World J Urol, 2017, 35(11):1689–99., DOI 10.1007/s00345-017- 2047-z
Inoue LY, Trock BJ, Partin AW, Carter HB, Etzioni R. Modeling grade progression in an active surveillance study. Stat Med, 2014, 33(6):930–9., DOI 10. 1002/sim.6003
Epstein JI, Egevad L, Humphrey PA, Montironi R, Group MotIIiDUP. Best practices recommendations in the application of immunohistochemistry in the prostate: Report from the international society of urologic pathology consensus conference. Am J Surg Pathol, 2014, 38(8):e6–e19., DOI 10.1097/PAS. 0000000000000238
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics, 1977, 33(1):159–74., DOI 10.2307/2529310
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Danneman D, Drevin L, Delahunt B, Samaratunga H, Robinson D, Bratt O, et al. Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: Nationwide trends 2000-2012. BJU Int, 2017, 119(1): 50–6., DOI 10.1111/bju.13458
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Mian BM, Lehr DJ,Moore CK, Fisher HA, Kaufman RP, Ross JS, et al. Role of prostate biopsy schemes in accurate prediction of Gleason scores. Urology, 2006, 67(2):379–83., DOI 10.1016/j.urology.2005.08.018
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Athanazio D, Gotto G, Shea-Budgell M, Yilmaz A, Trpkov K. Global Gleason grade groups in prostate cancer: Concordance of biopsy and radical prostatectomy grades and predictors of upgrade and downgrade. Histopathology, 2017, 70(7): 1098–106., DOI 10.1111/his.13179
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Egevad L, Norlen BJ, Norberg M. The value of multiple core biopsies for predicting the Gleason score of prostate cancer. BJU Int, 2001, 88(7):716–21., DOI 10.1046/j.1464-4096.2001.02419.x
Miyake H, Kurahashi T, Takenaka A, Hara I, Fujisawa M. Improved accuracy for predicting the Gleason score of prostate cancer by increasing the number of transrectal biopsy cores. Urol Int, 2007, 79(4):302–6., DOI 10.1159/ 000109713
Antunes AA, Leite KR, Dall’Oglio MF, Cury J, Srougi M. The effect of the number of biopsy cores on the concordance between prostate biopsy and prostatectomy Gleason score: A prostate volume-controlled study. Arch Pathol LabMed, 2008, 132(6):989–92., DOI 10.1043/1543-2165(2008)132[989:TEOTNO]2. 0.CO;2
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Hall GS, Kramer CE, Epstein JI. Evaluation of radical prostatectomy specimens. A comparative analysis of sampling methods. Am J Surg Pathol, 1992, 16(4):315–24., DOI 10.1097/00000478-199204000-00001
Cohen MB, Soloway MS, Murphy WM. Sampling of radical prostatectomy specimens. How much is adequate? Am J Clin Pathol, 1994, 101(3):250–2., DOI 10. 1093/ajcp/101.3.250
Hollenbeck BK, Bassily N, Wei JT, Montie JE, Hayasaka S, Taylor JM, et al. Whole mounted radical prostatectomy specimens do not increase detection of adverse pathological features. J Urol, 2000, 164(5):1583–6., DOI 10.1016/s0022- 5347(05)67033-4
Sehdev AE, Pan CC, Epstein JI. Comparative analysis of samplingmethods for grossing radical prostatectomy specimens performed for nonpalpable, stage T1c, prostatic adenocarcinoma. Hum Pathol, 2001, 32(5):494–9., DOI 10.1053/hupa. 2001.24322
Vainer B, Toft BG, Olsen KE, Jacobsen GK, Marcussen N. Handling of radical prostatectomy specimens: Total or partial embedding? Histopathology, 2011, 58(2): 211–6., DOI 10.1111/j.1365-2559.2011.03741.x
Llanos CA, Blieden C, Vernon SE. Processing radical prostatectomies: An alternate-slice method is comparable with total embedding. Ann Diagn Pathol, 2012, 16(4):284–7., DOI 10.1016/j.anndiagpath.2011.10.004
Kim K, Pak PJ, Ro JY, Shin D, Huh SJ, Cho YM. Limited sampling of radical prostatectomy specimens with excellent preservation of prognostic parameters of prostate cancer. Arch Pathol Lab Med, 2009, 133(8):1278–84., DOI 10.1043/1543- 2165-133.8.1278
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Bori R, Salamon F, Moczar C, Cserni G. Interobserver reproducibility of Gleason grading in prostate biopsy samples. Orv Hetil, 2013, 154(31):1219–25., DOI 10.1556/OH.2013.29659
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Mulay K, Swain M, Jaiman S, Gowrishankar S. Gleason scoring of prostatic carcinoma: Impact of a web-based tutorial on inter- and intra-observer variability. Indian J Pathol Microbiol, 2008, 51(1):22–5., DOI 10.4103/0377-4929.40385
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611157
EP 1611166
DI 10.3389/pore.2023.1611157
PG 10
ER
PT J
AU Leeha, M
Kanokwiroon, K
Laohawiriyakamol, S
Thongsuksai, P
AF Leeha, Marisa
Kanokwiroon, Kanyanatt
Laohawiriyakamol, Suphawat
Thongsuksai, Paramee
TI Immunohistochemistry-based molecular subtyping of triple-negative breast cancer and its prognostic significance
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; breast cancer; prognosis; triple-negative breast cancer; molecular subtype
ID immunohistochemistry; breast cancer; prognosis; triple-negative breast cancer; molecular subtype
AB Background: Immunohistochemistry (IHC)-based protein markers representing molecular subtypes are of great value for routine use. This study aimed to evaluate the frequency distributions of the molecular subtypes of triple-negative breast cancer (TNBC) using IHC-based surrogate markers and examined their prognostic value. Methods: Patients with TNBC treated at a university hospital in Southern Thailand were included in this study. Expression levels of androgen receptor, CD8, Forkhead box transcription factor C1, and Doublecortin-like kinase 1 were detected in tumor tissue to classify them into luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymallike (MES), and unclassifiable (UC) subtypes. The association between variables and disease-free survival (DFS) and overall survival (OS) was analyzed using Cox proportional hazards regression. Results: Among the 195 cases of TNBC, the frequency distribution of the IHCbased subtype was as follows: BLIS, 52.8%; LAR, 19.0%; IM, 17.4%; MES, 0.5%; and un-classifiable, 10.3%. BLIS subtype was significantly found in younger ages (mean: 49.6 years) than other subtypes (mean: 51–57.7 years). LAR and BLIS subtypes were significantly associated with poorer OS compared to the IM subtype in univariate analysis, however, only BLIS was significant in multivariate analysis (HR: 3.29, 95% CI: 1.01–10.72). IHC-based subtype was not found to be associated with DFS. Conclusion: This study revealed the differences in the proportion frequency of IHCbased TNBC subtypes in Thai patients compared to other populations. IHC-based molecular subtypingmay be beneficial for prognosis. However further refinement of the molecular classification of TNBC is needed for better clinical relevance.
C1 [Leeha, Marisa] Prince of Songkla University, Faculty of Medicine, Department of Biomedical Sciences and Biomedical EngineeringHat Yai, Songkhla, Thailand.
[Kanokwiroon, Kanyanatt] Prince of Songkla University, Faculty of Medicine, Department of Biomedical Sciences and Biomedical EngineeringHat Yai, Songkhla, Thailand.
[Laohawiriyakamol, Suphawat] Prince of Songkla University, Faculty of Medicine, Department of SurgeryHat Yai, Songkhla, Thailand.
[Thongsuksai, Paramee] Prince of Songkla University, Faculty of Medicine, Department of PathologyHat Yai, Songkhla, Thailand.
RP Thongsuksai, P (reprint author), Prince of Songkla University, Faculty of Medicine, Department of Pathology, Hat Yai, Thailand.
EM tparamee@gmail.com
CR Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71:209–49., DOI 10.3322/caac.21660
Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y,McCue P, et al. Differences in breast carcinoma characteristics in newly diagnosed african-American and caucasian patients: A single-institution compilation compared with the national cancer institute’s surveillance, epidemiology, and end results database. Cancer, 2007, 110:876–84., DOI 10.1002/cncr.22836
Hines LM, Risendal B, Byers T, Mengshol S, Lowery J, Singh M. Ethnic disparities in breast tumor phenotypic subtypes in Hispanic and non-Hispanic white women. J Womens Health, Larchmt,, 2011, 20:1543–50., DOI 10.1089/jwh. 2010.2558
Zhang W, Bai Y, Sun C, Lv Z, Wang S. Racial and regional disparities of triple negative breast cancer incidence rates in the United States: An analysis of 2011- 2019 NPCR and SEER incidence data. Front Public Health, 2022, 10:1058722., DOI 10.3389/fpubh.2022.1058722
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res, 2007, 13:4429–34., DOI 10.1158/1078-0432.CCR-06-3045
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Clin Invest, 2011, 121:2750–67., DOI 10.1172/JCI45014
Lehmann BD, Jovanovic B, Chen X, Estrada MV, Johnson KN, Shyr Y, et al. Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One, 2016, 11:e0157368., DOI 10.1371/ journal.pone.0157368
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Jiang YZ, Ma D, Suo C, Shi J, Xue M, Hu X, et al. Genomic and transcriptomic landscape of triple-negative breast cancers: Subtypes and treatment strategies. Cancer Cell, 2019, 35:428–40., DOI 10.1016/j.ccell.2019. 02.001
Zhao S, Ma D, Xiao Y, Li XM, Ma JL, Zhang H, et al. Molecular subtyping of triple-negative breast cancers by immunohistochemistry: Molecular basis and clinical relevance. Oncologist, 2020, 25:e1481–e1491., DOI 10.1634/theoncologist.2019-0982
Niyomnaitham S, Parinyanitikul N, Roothumnong E, Jinda W, Samarnthai N, Atikankul T, et al. Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene. PeerJ, 2019, 7:e6501., DOI 10.7717/peerj.6501
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611162
EP 1611171
DI 10.3389/pore.2023.1611162
PG 10
ER
PT J
AU Gyulai, M
Megyesfalvi, Zs
Reiniger, L
Harko, T
Ferencz, B
Karsko, L
Agocs, L
Fillinger, J
Dome, B
Szallasi, Z
Moldvay, J
AF Gyulai, Marton
Megyesfalvi, Zsolt
Reiniger, Lilla
Harko, Tunde
Ferencz, Bence
Karsko, Luca
Agocs, Laszlo
Fillinger, Janos
Dome, Balazs
Szallasi, Zoltan
Moldvay, Judit
TI PD-1 and PD-L1 expression in rare lung tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE adenoid cystic carcinoma; mucoepidermoid carcinoma; programmed cell death ligand-1 (PD-L1); programmed cell death-1 (PD-1); rare lung tumors
ID adenoid cystic carcinoma; mucoepidermoid carcinoma; programmed cell death ligand-1 (PD-L1); programmed cell death-1 (PD-1); rare lung tumors
AB Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD- 1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PDL1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PDL1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PDL1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.
C1 [Gyulai, Marton] County Hospital of PulmonologyTorokbalint, Hungary.
[Megyesfalvi, Zsolt] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Reiniger, Lilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Harko, Tunde] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Ferencz, Bence] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Karsko, Luca] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Agocs, Laszlo] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Fillinger, Janos] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Dome, Balazs] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Szallasi, Zoltan] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute of PulmonologyBudapest, Hungary.
RP Moldvay, J (reprint author), National Koranyi Institute of Pulmonology, Budapest, Hungary.
EM drmoldvay@hotmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611164
EP 1611172
DI 10.3389/pore.2023.1611164
PG 9
ER
PT J
AU Wiedemann,
Szita, RV
Horvath, R
Szederjesi, A
Sebo, A
Toth, DA
Masszi, T
Varga, G
AF Wiedemann, Adam
Szita, Reka Virag
Horvath, Robert
Szederjesi, Attila
Sebo, Attila
Toth, David Andras
Masszi, Tamas
Varga, Gergely
TI Soluble B-cell maturation antigen as a monitoring marker for multiple myeloma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; monitoring; monoclonal gammopathie; soluble B-cell maturation antigen; BCMA
ID multiple myeloma; monitoring; monoclonal gammopathie; soluble B-cell maturation antigen; BCMA
AB Objective: Response to treatment in multiple myeloma (MM) is routinely measured by serum and urine M-protein and free light chain (FLC), as described by the International Myeloma Working Group (IMWG) consensus statement. A non-negligible subgroup of patients however present without measurable biomarkers, others become oligo or non-secretory during recurrent relapses. The aim of our research was to evaluate soluble B-cell maturation antigen (sBCMA) as a monitoring marker measured concurrent with the standard monitoring in MM patients at diagnosis, at relapse and during follow up, in order to establish its potential usefulness in oligo and nonsecretory disease. Method: sBCMA levels were measured in 149 patients treated for plasma cell dyscrasia (3 monoclonal gammopathy of unknown significance, 5 smoldering myeloma, 7 plasmacytoma, 8 AL amyloidosis and 126 MM) and 16 control subjects using a commercial ELISA kit. In 43 newly diagnosed patients sBCMA levels were measured at multiple timepoints during treatment, and compared to conventional IMWG response and progression free survival (PFS). Results: sBCMA levels among control subjects were significantly lower than among newly diagnosed or relapsed MM patients [20.8 (14.7–38.7) ng/mL vs. 676 (89.5–1,650) and 264 (20.7–1,603) ng/mL, respectively]. Significant correlations were found between sBCMA and the degree of bone marrow plasma cell infiltration. Out of the 37 newly diagnosed patients who have reached partial response or better per IMWG criteria, 33 (89%) have had at least a 50% drop in sBCMA level by therapy week 4. Cohorts made similarly to IMWG response criteria—achieving a 50% or 90% drop in sBCMA levels compared to level at diagnosis—had statistically significant differences in PFS. Conclusion: Our results confirmed that sBCMA levels are prognostic at important decision points in myeloma, and the percentage of BCMA change is predictive for PFS. This highlights the great potential use of sBCMA in oligoand non-secretory myeloma.
C1 [Wiedemann, Adam] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Szita, Reka Virag] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Horvath, Robert] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Szederjesi, Attila] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Sebo, Attila] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Toth, David Andras] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Masszi, Tamas] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Varga, Gergely] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
RP Varga, G (reprint author), Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary.
EM vargager@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611171
EP 1611178
DI 10.3389/pore.2023.1611171
PG 8
ER
PT J
AU Zhang, L
Zhang, X
Wu, B
Han, X
Guo, C
Li, B
Jing, H
Cheng, W
AF Zhang, Lei
Zhang, Xuefei
Wu, Bolin
Han, Xue
Guo, Cunli
Li, Bo
Jing, Hui
Cheng, Wen
TI Prognostic value of albumin-bilirubin score in pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chemotherapy; pancreatic cancer; liver metastasis; radiofrequency ablation; pancreatoduodenectomy
ID chemotherapy; pancreatic cancer; liver metastasis; radiofrequency ablation; pancreatoduodenectomy
AB Objective: The current study aimed to investigate the prognostic value of albumin-bilirubin (ALBI) score in predicting clinical outcomes of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Methods: This retrospective study included 90 pancreatic cancer patients after pancreatoduodenectomy with liver metastasis from January 2012 to December 2018. In this study, the Chi-square or Fisher’s exact tests, the receiver operating characteristic (ROC) curve, Kaplan-Meier method and Log-rank test, univariate and multivariate Cox proportional hazard regression analyses, nomogram, calibration curves and decision curve analysis were used for all statistical analysis. Results: We analyzed the optimal cut-off value of ALBI by ROC curve, and the optimal cut-off value was −2.60. According to ALBI score, these patients were divided into two groups: low ALBI group (n = 33) and high ALBI group (n = 57). Patients with low ALBI score was significantly related to longer progression free survival (PFS) (p = 0.0002, HR: 3.039, 95% CI: 1.772–5.210) and overall survival (OS) (p = 0.0005, HR: 2.697, 95% CI: 1.539–4.720). The 1-, 3-, and 5-year PFS and OS rates in low ALBI group were higher than those in high ALBI group. ALBI was a potential independent prognostic factor for pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Moreover, the nomogram was used to predict the 1-, 3-, and 5-year survival probabilities of PFS and OS. The calibration curve shown that the prediction line matched the reference line well for postoperative 3-year PFS and OS. The DCA shown that nomogram model was better than the only ALBI, and indicated the ability for clinical decision-making, especially in 1-year PFS, and 3-, 5-year OS. Conclusion: ALBI is a potential independent factor for PFS and OS, and can predict the prognosis of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.
C1 [Zhang, Lei] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Zhang, Xuefei] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Wu, Bolin] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Han, Xue] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Guo, Cunli] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Li, Bo] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Jing, Hui] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
[Cheng, Wen] Harbin Medical University Cancer Hospital, Department of UltrasoundHarbin, China.
RP Cheng, W (reprint author), Harbin Medical University Cancer Hospital, Department of Ultrasound, Harbin, China.
EM chengwen@hrbmu.edu.cn
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611175
EP 1611188
DI 10.3389/pore.2023.1611175
PG 14
ER
PT J
AU Zhang, G
Hao, Y
Chen, L
Li, Z
Gao, L
Tian, J
Qiao, Q
Zhang, J
AF Zhang, Guangwen
Hao, Yongfei
Chen, Ling
Li, Zengshan
Gao, Langlang
Tian, Jian
Qiao, Qing
Zhang, Jinsong
TI Expression of aquaporin 1, 3 and 5 in colorectal carcinoma: correlation with clinicopathological characteristics and prognosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE biomarker; prognosis; clinical features; colorectal cancer; aquaporin
ID biomarker; prognosis; clinical features; colorectal cancer; aquaporin
AB Background: Prognostic biomarkers in colorectal carcinoma (CRC) have an important role in therapeutic strategy. Studies have shown that high expression of Aquaporin (AQP) is associated with poor prognosis in a variety of human tumors. AQP is involved in the initiation and development of CRC. The present study aimed to investigate the correlation between the expression of AQP1, 3 and 5 and clinicopathological features or prognosis in CRC. Methods: The AQP1, 3 and 5 expressions were analyzed based on the immunohistochemical staining of tissue microarray specimens including 112 patients with CRC between June 2006 and November 2008. The expression score of AQP (Allred_score and H_score) was digitally obtained with Qupath software. Patients were divided into high or low expression subgroups based on the optimal cut-off values. The relationship between expression of AQP and clinicopathological characteristics were evaluated using chi-square test, t-test, or one-way ANOVA, when appropriate. Survival analysis of 5-year progression free survival (PFS) and overall survival (OS) was performed with timedependent ROC, Kaplan-Meier curves, univariate and multivariate COX analysis. Results: The AQP1, 3 and 5 expressions were associated with regional lymph node metastasis, histological grading, and tumor location in CRC, respectively (p < 0.05). Kaplan-Meier curves showed that patients with high AQP1 expression had worse 5-year PFS than those with low AQP1 expression (Allred_score: 47% vs. 72%, p = 0.015; H_score: 52% vs. 78% p = 0.006), as well as 5-year OS (Allred_score: 51% vs. 75%, p = 0.005; H_score: 56% vs. 80%, p = 0.002). Multivariate Cox regression analysis indicated that AQP1 expression was an independent risk prognostic factor (p = 0.033, HR = 2.274, HR95% CI: 1.069–4.836). There was no significant correlation between the expression of AQP3 and 5 and the prognosis. Conclusion: The AQP1, 3 and 5 expressions correlate with different clinicopathological characteristics and the AQP1 expression may be a potential biomarker of prognosis in CRC.
C1 [Zhang, Guangwen] Fourth Military Medical University, Xijing Hospital, Department of RadiologyXi’an, Shaanxi, China.
[Hao, Yongfei] Fourth Military Medical University, Xijing Hospital, Department of RadiologyXi’an, Shaanxi, China.
[Chen, Ling] Fourth Military Medical University, Xijing Hospital, Department of PathologyXi’an, Shaanxi, China.
[Li, Zengshan] Fourth Military Medical University, Xijing Hospital, Department of PathologyXi’an, Shaanxi, China.
[Gao, Langlang] Fourth Military Medical University, Xijing Hospital, Department of RadiologyXi’an, Shaanxi, China.
[Tian, Jian] Fourth Military Medical University, Xijing Hospital, Department of RadiologyXi’an, Shaanxi, China.
[Qiao, Qing] Fourth Military Medical University, Tangdu Hospital, Department of general surgeryXi’an, Shaanxi, China.
[Zhang, Jinsong] Fourth Military Medical University, Xijing Hospital, Department of RadiologyXi’an, Shaanxi, China.
RP Zhang, J (reprint author), Fourth Military Medical University, Xijing Hospital, Department of Radiology, Xi’an, China.
EM stspine@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611179
EP 1611188
DI 10.3389/pore.2023.1611179
PG 10
ER
PT J
AU Tan, S
Nemeth, P
AF Tan, Songwen
Nemeth, Peter
TI Editorial: In vivo and in vitro models for research in pathology
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Editorial
DE analytical pathology; pathogenesis; tumor diagnosis; in vivo techniques; molecular pathology
ID analytical pathology; pathogenesis; tumor diagnosis; in vivo techniques; molecular pathology
C1 [Tan, Songwen] Central South University, Xiangya School of Pharmaceutical SciencesChangsha, China.
[Nemeth, Peter] University of Pecs, Faculty of Medicine, Department of Immunology and BiotechnologyPecs, Hungary.
RP Tan, S (reprint author), Central South University, Xiangya School of Pharmaceutical Sciences, Changsha, China.
EM stan0309@uni.sydney.edu.au
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611196
EP 1611198
DI 10.3389/pore.2023.1611196
PG 3
ER
PT J
AU Zhang, L
Yuan, P
Cao, Q
Mu, J
Ying, J
Guo, Ch
AF Zhang, Letian
Yuan, Pei
Cao, Qi
Mu, Jiali
Ying, Jianming
Guo, Changyuan
TI Case report: A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE breast cancer; clear cell renal cell carcinoma; tumor-to-tumor metastasis; rare case; metastatic lobular breast carcinoma
ID breast cancer; clear cell renal cell carcinoma; tumor-to-tumor metastasis; rare case; metastatic lobular breast carcinoma
AB Tumor-to-tumor metastasis is a rare phenomenon. Although renal cell carcinoma is the most common recipient tumor, metastatic lobular breast carcinoma to clear cell renal cell carcinoma is even rarer, with only one case reported to date. We present a 66-year-old female patient with an invasive lobular carcinoma history who was admitted to the hospital with a right renal mass. The patient received partial nephrectomy. The final established diagnosis is lobular breast carcinoma metastasizing to clear cell renal cell carcinoma (ccRCC). Thus, although rare, the simultaneous or consecutive find of a renal mass in follow-up should be carefully evaluated, especially in high-risk patients, including women with an advanced breast cancer history, as in this scenario.
C1 [Zhang, Letian] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Yuan, Pei] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Cao, Qi] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Mu, Jiali] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Ying, Jianming] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Guo, Changyuan] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
RP Guo, Ch (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of Pathology, Beijing, China.
EM guocycicams@sina.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611204
EP 1611207
DI 10.3389/pore.2023.1611204
PG 4
ER
PT J
TI Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; cholangiocarcinoma; tumor budding; prediction; disease-free survival
ID prognosis; cholangiocarcinoma; tumor budding; prediction; disease-free survival
AB Background: Tumor budding is considered a prognostic factor in several solid cancer types. However, we lack comprehensive information on the importance of tumor budding in cholangiocarcinoma. Therefore, we aimed to assess the prognostic value of tumor budding in intrahepatic and extrahepatic cholangiocarcinomas and to evaluate its correlations with other clinicopathological parameters. Methods: We monitored 219 patients who underwent surgery for intrahepatic or extrahepatic cholangiocarcinoma at the Pusan National University Hospital between 2012 and 2021. Tumor budding was evaluated using the International Tumor Budding Consensus Conference scoring system. Tumor budding was classified into low (0–4), intermediate (5–9), and high (≥10). For statistical analysis, tumor budding was divided into two groups based on the cut-off value of 10 (lower: 0–9 vs. higher: ≥10). The correlations between clinicopathological parameters were examined using the chi-square and Fisher’s exact test. The prognostic values of the variables were analyzed using the log-rank test and Cox regression analysis. Results: Low, intermediate, and high tumor buddings were identified in 135 (61.6%), 63 (28.8), and 21 (9.6%), patients, respectively. Higher tumor budding was related to the presence of lymphatic invasion (p = 0.017), higher tumor grade (p = 0.001), higher N category (p = 0.034). In the univariable and multivariable analyses, higher tumor budding was associated with shorter disease-free survival in 97 (44.3%) patients who underwent R0 resection (p < 0.001 and p = 0.011). Tumor budding did not significantly correlate with disease-specific survival in entire patients. Conclusion: Tumor budding may serve as a prognostic factor for intrahepatic and extrahepatic cholangiocarcinomas treated with R0 resection.
CR Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: Epidemiology and risk factors. Liver Int, 2019, 39:19–31., DOI 10.1111/liv.14095
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Imai T. The growth of human carcinoma: A morphological analysis. Fukuoka Igaku Zasshi, 1954, 45:72–102.
De Smedt L, Palmans S, Sagaert X. Tumour budding in colorectal cancer: What do we know and what can we do? Virchows Arch, 2016, 468(4):397–408., DOI 10. 1007/s00428-015-1886-5
Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference, ITBCC, 2016. Mod Pathol, 2017, 30(9):1299–311., DOI 10.1038/modpathol.2017.46
Karamitopoulou E, Wartenberg M, Zlobec I, Cibin S, Worni M, Gloor B, et al. Tumour budding in pancreatic cancer revisited: Validation of the ITBCC scoring system. Histopathology, 2018, 73(1):137–46., DOI 10.1111/ his.13508
Kim HN, Lee SY, Kim BH, Kim CY, Kim A, Kim H. Prognostic value of tumor budding in gallbladder cancer: Application of the international tumor budding consensus conference scoring system. Virchows Arch, 2021, 478(6):1071–8., DOI 10. 1007/s00428-020-03012-2
Lohneis P, Hieggelke L, Gebauer F, Ball M, Bruns C, Buttner R, et al. Tumor budding assessed according to the criteria of the International Tumor Budding Consensus Conference determines prognosis in resected esophageal adenocarcinoma. Virchows Arch, 2021, 478(3):393–400., DOI 10.1007/s00428- 020-02897-3
Szalai L, Jakab A, Kocsmar I, Szirtes I, Kenessey I, Szijarto A, et al. Prognostic ability of tumor budding outperforms poorly differentiated clusters in gastric cancer. Cancers, Basel,, 2022, 14(19):4731., DOI 10.3390/ cancers14194731
Agostini-Vulaj D, Cates JMM, Bratton LE, Gonzalez RS. Increasing tumor budding in cholangiocarcinoma is associated with decreased diseasespecific survival. Hum Pathol, 2021, 111:75–83., DOI 10.1016/j.humpath. 2021.03.004
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Lugli A, Zlobec I, Berger MD, Kirsch R, Nagtegaal ID. Tumour budding in solid cancers. Nat Rev Clin Oncol, 2021, 18(2):101–15., DOI 10.1038/s41571-020- 0422-y
Tanaka M, Kunita A, Yamagishi M, Katoh H, Ishikawa S, Yamamoto H, et al. KRAS mutation in intrahepatic cholangiocarcinoma: Linkage with metastasis-free survival and reduced E-cadherin expression. Liver Int, 2022, 42(10):2329–40., DOI 10.1111/liv.15366
Zlobec I, Bachli M, Galuppini F, Berger MD, Dawson HE, Nagtegaal ID, et al. Refining the ITBCC tumor budding scoring system with a "zero-budding" category in colorectal cancer. Virchows Arch, 2021, 479(6):1085–90., DOI 10.1007/s00428- 021-03090-w
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611216
EP 1611225
DI 10.3389/pore.2023.1611216
PG 10
ER
PT J
AU Lv, J
Chen, P
Wu, J
Hu, C
AF Lv, Jing
Chen, Peirui
Wu, Jianqiang
Hu, Caihong
TI Prognostic value of pretreatment Controlling Nutritional Status score in esophageal cancer: a meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE meta-analysis; prognosis; esophageal cancer; pretreatment; Controlling Nutritional Status score
ID meta-analysis; prognosis; esophageal cancer; pretreatment; Controlling Nutritional Status score
AB Background and purpose: The association between the pretreatment Controlling Nutritional Status (CONUT) score and the prognosis of esophageal cancer patients remains unclear. The aim of this meta-analysis was to further elucidate the prognostic role of the pretreatment CONUT score in esophageal cancer based on current evidence. Methods: The PubMed, Embase, Web of Science and CNKI databases were searched up to 27 September 2022. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS)/cancer-specific survival (CSS), and the hazard ratio (HR) and 95% confidence interval (CI) were pooled for analysis. Results: A total of 11 retrospective studies involving 3,783 participants were included. The pooled results demonstrated that a higher pretreatment CONUT score was significantly related to poor OS (HR = 1.82, 95% CI: 1.31–2.54, p < 0.001), and subgroup analysis stratified by pathological type showed similar results. In addition, the pretreatment CONUT score was associated with poor PFS (HR = 1.19, 95% CI: 1.10–1.28, p < 0.001) and CSS (HR = 2.67, 95% CI: 1.77–4.02, p < 0.001). Conclusion: The pretreatment CONUT score was predictive of worse prognosis in esophageal cancer, and patients with a higher CONUT score showed worse survival.
C1 [Lv, Jing] People’s Hospital of Deyang City, Department of Thoracic SurgeryDeyang, China.
[Chen, Peirui] People’s Hospital of Deyang City, Department of Thoracic SurgeryDeyang, China.
[Wu, Jianqiang] People’s Hospital of Deyang City, Department of Thoracic SurgeryDeyang, China.
[Hu, Caihong] People’s Hospital of Deyang City, Department of Thoracic SurgeryDeyang, China.
RP Hu, C (reprint author), People’s Hospital of Deyang City, Department of Thoracic Surgery, Deyang, China.
EM 523161885@qq.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611221
EP 1611230
DI 10.3389/pore.2023.1611221
PG 10
ER
PT J
AU Reisz, Z
Radics, LB
Nemes, P
Laxton, R
Kaizer, L
Gabor, MK
Novak, T
Barzo, P
Al-Sarraj, S
Bodi, I
AF Reisz, Zita
Radics, Laszlo Bence
Nemes, Peter
Laxton, Ross
Kaizer, Laszlo
Gabor, Mita Krisztina
Novak, Timea
Barzo, Pal
Al-Sarraj, Safa
Bodi, Istvan
TI Case Report: Brainstem angiocentric glioma presenting in a toddler child–diagnostic and therapeutic challenges
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE paediatric brainstem glioma; angiocentric glioma; MYB:QKI fusion; DNA methylation profiling; RNA sequencing
ID paediatric brainstem glioma; angiocentric glioma; MYB:QKI fusion; DNA methylation profiling; RNA sequencing
AB Introduction: Angiocentric gliomas (AG) in brainstem location are exceedingly rare and might cause differential diagnostic problems and uncertainty regarding the best therapeutic approach. Hereby, we describe the clinicopathological findings in a brainstem AG presenting in a toddler child and review the literature. Case report: A 2-year-old boy presented with 5 weeks history of gait disturbances, frequent falls, left-sided torticollis and swallowing problems. MRI head showed a T2-hyperintense, partly exophytic mass lesion centred in the pontomedullary region, raising the possibility of diffuse midline glioma. The exophytic component was partially resected by suboccipital craniotomy, leaving intact the infiltrative component. Ventriculoperitoneal shunt was implanted due to postoperative hydrocephalus. Histological examination revealed a moderately cellular tumour consisted of bland glial cells infiltrating the brain parenchyma and radially arranged around the blood vessels. By immunohistochemistry, the tumour strongly expressed S100 and GFAP in addition to intense nestin positivity, while OLIG2 was negative in the perivascular tumour cells. DNA methylation array profiled the tumour as “methylation class diffuse astrocytoma, MYB or MYBL1-altered subtype B (infratentorial)” and an in-frame MYB::QKI fusion was identified by RNA sequencing, confirming the diagnosis of angiocentric glioma. The patient has been initially treated with angiogenesis inhibitor and mTOR inhibitor, and now he is receiving palliative vinblastine. He is clinically stable on 9 months follow-up. Conclusion: Brainstem AG may cause a diagnostic problem, and the surgical and oncological management is challenging due to unresectability and lack of response to conventional chemo-radiation. In the future, genetically-tailored therapies might improve the prognosis.
C1 [Reisz, Zita] King’s College Hospital, Clinical NeuropathologyLondon, UK.
[Radics, Laszlo Bence] University of Szeged, Department of PathologySzeged, Hungary.
[Nemes, Peter] University of Szeged, Department of NeurosurgerySzeged, Hungary.
[Laxton, Ross] King’s College Hospital, Clinical NeuropathologyLondon, UK.
[Kaizer, Laszlo] University of Szeged, Department of PathologySzeged, Hungary.
[Gabor, Mita Krisztina] University of Szeged, Department of PediatricsSzeged, Hungary.
[Novak, Timea] University of Szeged, Department of RadiologySzeged, Hungary.
[Barzo, Pal] University of Szeged, Department of NeurosurgerySzeged, Hungary.
[Al-Sarraj, Safa] King’s College Hospital, Clinical NeuropathologyLondon, UK.
[Bodi, Istvan] King’s College Hospital, Clinical NeuropathologyLondon, UK.
RP Bodi, I (reprint author), King’s College Hospital, Clinical Neuropathology, London, UK.
EM istvan.bodi@nhs.net
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611231
EP 1611237
DI 10.3389/pore.2023.1611231
PG 7
ER
PT J
AU Cegledi, A
Dolgos, J
Fekete, M
Gopcsa, L
Varkonyi, A
Vilimi, B
Mikala, G
Bodo, I
AF Cegledi, Andrea
Dolgos, Janos
Fekete, Monika
Gopcsa, Laszlo
Varkonyi, Andrea
Vilimi, Beata
Mikala, Gabor
Bodo, Imre
TI Delayed spontaneous remission of acquired factor V inhibitor refractory to immunosuppressive therapy with pregnancy-associated improvement
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE factor V inhibitor; coagulopathy; gestation; bleeding disorder; autoimmune
ID factor V inhibitor; coagulopathy; gestation; bleeding disorder; autoimmune
AB Introduction: Acquired factor V inhibitor (AFVI) is a rare autoimmune bleeding disorder. The treatment of AFVI is challenging, and patients often require both bleeding control and inhibitor eradication. Methods: We conducted a retrospective analysis of the medical records of a 35-year-old Caucasian woman who presented with severe AFVI-induced bleeding and subsequent immunosuppressive therapy. Results: To provide haemostasis, rFVIIa was given with good efficacy. The patient was treated with various combinations of immunosuppressive regimens over the course of 2.5 years, including plasmapheresis plus immunoglobulins, dexamethasone + rituximab, cyclophosphamide + dexamethasone + rituximab + cyclosporine, cyclosporin + sirolimus + cyclophosphamide + dexamethasone, bortezomib + sirolimus + methylprednisolone, and sirolimus + mycophenolate mofetil. Although these treatment modalities resulted in intermittent partial reversals of AFVI over 2.5 years, eventually the inhibitor became therapy-resistant. However, following the discontinuation of all immunosuppressive therapy, the patient experienced a partial spontaneous remission, which was followed by a pregnancy. During the pregnancy, the FV activity increased to 54% and the coagulation parameters returned to normal levels. The patient underwent Caesarean section without any bleeding complications and delivered a healthy child. Discussion: The use of an activated bypassing agent for bleeding control is effective in patients with severe AFVI. The presented case is unique because the treatment regimens included multiple combinations of immunosuppressive agents. This demonstrates that AFVI patients may undergo spontaneous remission even after multiple courses of ineffective immunosuppressive protocols. Additionally, pregnancy-associated improvement of AFVI is an important finding that warrants further investigation.
C1 [Cegledi, Andrea] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Dolgos, Janos] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Fekete, Monika] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Gopcsa, Laszlo] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Varkonyi, Andrea] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Vilimi, Beata] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Bodo, Imre] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
RP Cegledi, A (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Budapest, Hungary.
EM ceglediandi@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611250
EP 1611257
DI 10.3389/pore.2023.1611250
PG 8
ER
PT J
AU Wang, X
Wei, X
AF Wang, Xiaoxue
Wei, Xin
TI Case report: Vulval sebaceous carcinoma: a report of two cases and literature review focus on treatment and survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE extraocular sebaceous carcinoma; vulval sebaceous carcinoma; surgery; adjuvant therapy; prognosis
ID extraocular sebaceous carcinoma; vulval sebaceous carcinoma; surgery; adjuvant therapy; prognosis
AB Background: Extraocular sebaceous carcinoma (SC) arising in the vulva is extremely rare that no treatment consensus has been well-defined. Case presentation: We here presented two cases of vulval SC in a 31-year-old and a 62-year-old woman, respectively. Radical wide local excision was performed with free margin and they received no postoperative adjuvant therapy. No evidence of disease was detected after follow-ups for 12 months and 49 months, respectively. A comprehensive literature review of vulval SC was further conducted and other ten cases were included. The mean age was 55.9 years, nine patients were diagnosed with FIGO stage I diseases while the remaining three patients had metastatic lesions at initial diagnosis. Surgery was the mainstay treatment option that 11 (91.7%) underwent surgical resection, of which 5 patients received inguinal lymphadenectomy and 2 patients showed lymph nodes involved. Radiotherapy and chemotherapy were given in 2 and 1 patient, respectively. Two patients experienced recurrence within 1 year after initial therapy. At the final follow-up, ten patients had no evidence of disease, one patient was alive with the disease, and only one died of the disease. Conclusion: Radical wide local excision may be preferred in early-stage vulval SC and utilization of sentinel lymph node sampling should be recommended. Postoperative adjuvant therapy may be spared in patients with negative surgical margin and absence of lymph node involvement. Treatment of vulval SC referring to the guidelines of vulvar cancer should be administered in case of positive margins or metastatic disease.
C1 [Wang, Xiaoxue] Peking Union Medical College Hospital, Department of Obstetrics and GynecologyBeijing, China.
[Wei, Xin] University of South China, Hengyang Medical School, The Affiliated Changsha Central Hospital, Department of Obstetrics and GynecologyChangsha, China.
RP Wei, X (reprint author), University of South China, Hengyang Medical School, The Affiliated Changsha Central Hospital, Department of Obstetrics and Gynecology, Changsha, China.
EM weixin1017a@163.com
CR Knackstedt T, Samie FH. Sebaceous carcinoma: A review of the scientific literature. Curr Treat Options Oncol, 2017, 18(8):47., DOI 10.1007/s11864-017-0490-0
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Tripathi R, Chen Z, Li L, Bordeaux JS. Incidence and survival of sebaceous carcinoma in the United States. J Am Acad Dermatol, 2016, 75(6):1210–5., DOI 10. 1016/j.jaad.2016.07.046
Yamamoto A, Chigusa Y, Fujimoto M, Yamanoi K, Minamiguchi S, Yasuda E, et al. Sebaceous carcinoma of the vulva treated with sentinel lymph node biopsy: A case report and literature review. Int Cancer Conf J, 2021, 10(3):239–43., DOI 10. 1007/s13691-021-00488-w
Kawamoto M, Fukuda Y, Kamoi S, Sugisaki Y, Yamanaka N. Sebaceous carcinoma of the vulva. Pathol Int, 1995, 45(10):767–73., DOI 10.1111/j.1440-1827.1995.tb03395.x
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Bhaijee F, Brown AS. Muir-Torre syndrome. Arch Pathol Lab Med, 2014, 138(12):1685–9., DOI 10.5858/arpa.2013-0301-RS
Chang AY, Miller CJ, Elenitsas R, Newman JG, Sobanko JF. Management considerations in extraocular sebaceous carcinoma. Dermatol Surg, 2016, 42(1): S57–65., DOI 10.1097/DSS.0000000000000575
Bogani G, Leone Roberti Maggiore U, Raspagliesi F. Lynch syndrome - muirtorre variant: Implication in gynecologic oncology. J Gynecol Oncol, 2018, 29(5): e84., DOI 10.3802/jgo.2018.29.e84
Dores GM, Curtis RE, Toro JR, Devesa SS, Fraumeni JF, Jr. Incidence of cutaneous sebaceous carcinoma and risk of associated neoplasms: Insight into muir-torre syndrome. Cancer, 2008, 113(12):3372–81., DOI 10.1002/cncr.23963
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611259
EP 1611265
DI 10.3389/pore.2023.1611259
PG 7
ER
PT J
AU Varga, Zs
Biro, A
Torok, M
Toth, D
AF Varga, Zsolt
Biro, Adrienn
Torok, Miklos
Toth, Dezso
TI A combined approach for individualized lymphadenectomy in gastric cancer patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; surgery; lymphadenectomy; sentinel; Maruyama
ID gastric cancer; surgery; lymphadenectomy; sentinel; Maruyama
AB Introduction: Gastric cancer ranks as the fifth most common cancer globally. The presence of lymph node metastasis is a significant prognostic factor influencing survival. Postoperative morbidity and nodal staging accuracy are heavily affected by the extent of lymph node dissection. Our study aimed to explore the potential integration of two contemporary methods, sentinel node navigation surgery (SNNS) and the Maruyama Computer Program (MCP), to improve the accuracy of nodal staging. Materials and methods: We conducted a prospective data collection involving patients with gastric adenocarcinoma from 2008 to 2018 at the Department of Surgery, University of Debrecen, Hungary. Data from 100 consecutive patients were collected. The primary and secondary endpoints included evaluating the rate of node-negative patients and the diagnostic accuracy of our combined approach. Results: Sentinel node mapping was successful in 97 out of 100 patients. We found that using the threshold value of the Maruyama Index (MI) ≥ 28, all metastatic stations of sentinel-node-negative patients could be identified. Our method achieved 100% sensitivity and negative predictive value, with a specificity of 60.42% (95% CI = 46.31%–72.98%). Discussion: The combined application of SNNS and MCP has proven to be an effective diagnostic technique in the synergistic approach for identifying metastasis-positive lymph node stations. Despite its limitations, this combination may assist clinicians in customizing lymphadenectomy for gastric cancer patients.
C1 [Varga, Zsolt] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
[Biro, Adrienn] Somogy Megyei Kaposi Mor Oktato Korhaz, Sebeszeti OsztalyKaposvar, Hungary.
[Torok, Miklos] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Toth, Dezso] University of Debrecen, Department of Surgery and Operative TechniquesDebrecen, Hungary.
RP Toth, D (reprint author), University of Debrecen, Department of Surgery and Operative Techniques, Debrecen, Hungary.
EM dr.toth.dezso@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611270
EP 1611279
DI 10.3389/pore.2023.1611270
PG 10
ER
PT J
AU Ogasawara, H
Yoshizawa, T
Oshima, K
Ogasawara, K
Kubota, Sh
Goto, Sh
Morohashi, S
Wakiya, T
Kimura, N
Ishido, K
Kijima, H
Hakamada, K
AF Ogasawara, Hirokazu
Yoshizawa, Tadashi
Oshima, Kiyoko
Ogasawara, Kenta
Kubota, Shunsuke
Goto, Shintaro
Morohashi, Satoko
Wakiya, Taiichi
Kimura, Norihisa
Ishido, Keinosuke
Kijima, Hiroshi
Hakamada, Kenichi
TI Three-dimensional analysis of perineural invasion in extrahepatic cholangiocarcinoma using tissue clearing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tissue clearing; three-dimensional; perineural invasion; cholangiocarcinoma; iDISCO
ID tissue clearing; three-dimensional; perineural invasion; cholangiocarcinoma; iDISCO
AB Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.
C1 [Ogasawara, Hirokazu] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Yoshizawa, Tadashi] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Oshima, Kiyoko] Johns Hopkins School of Medicine, Department of PathologyBaltimore, MD, USA.
[Ogasawara, Kenta] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Kubota, Shunsuke] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Goto, Shintaro] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Morohashi, Satoko] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Wakiya, Taiichi] Hirosaki University Graduate School of Medicine, Department of Gastroenterological SurgeryHirosaki, Aomori, Japan.
[Kimura, Norihisa] Hirosaki University Graduate School of Medicine, Department of Gastroenterological SurgeryHirosaki, Aomori, Japan.
[Ishido, Keinosuke] Hirosaki University Graduate School of Medicine, Department of Gastroenterological SurgeryHirosaki, Aomori, Japan.
[Kijima, Hiroshi] Hirosaki University Graduate School of Medicine, Department of Pathology and BioscienceHirosaki, Aomori, Japan.
[Hakamada, Kenichi] Hirosaki University Graduate School of Medicine, Department of Gastroenterological SurgeryHirosaki, Aomori, Japan.
RP Yoshizawa, T (reprint author), Hirosaki University Graduate School of Medicine, Department of Pathology and Bioscience, Hirosaki, Japan.
EM tyoshi@hirosaki-u.ac.jp
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2023
VL 29
IS 2
BP 1611284
EP 1611290
DI 10.3389/pore.2023.1611284
PG 7
ER
PT J
AU Han, G
Sun, Ch
Cui, L
Huang, Y
Yu, L
Liu, Sh
Tao, M
AF Han, Guohu
Sun, Changchun
Cui, Lihua
Huang, Yufeng
Yu, Lijiang
Liu, Shenzha
Tao, Min
TI Efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment in HER-2 negative advanced gastric cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apatinib; deep hyperthermia; gastric cancer; efficacy evaluation; prognosis
ID apatinib; deep hyperthermia; gastric cancer; efficacy evaluation; prognosis
AB Aim: To observe the efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment for patients with human epidermal growth factor receptor 2 (HER-2) negative advanced gastric cancer. Methods: 80 eligible patients with HER-2 negative advanced gastric cancer admitted to Jingjiang People’s Hospital Affiliated with Yangzhou Universityfrom March 2021 to March 2022 were selected, and they were divided into the control group (n = 40, apatinib) and experimental group (n = 40, apatinib plus deep hyperthermia) on the basis of random number table method. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and vascular endothelial growth factor (VEGF) were monitored, and the efficacy of the two groups was analyzed by referring to Karnofsky performance status (KPS), overall survival (OS) and disease control rate (DCR) before and after treatment. Results: The levels of CEA, CA199, and VEGF in both groups were lower after treatment than before (p < 0.05), and lower (CEA: 8.85 ± 1.36 vs. 12.87 ± 1.23, CA199: 34.19 ± 4.68 vs. 50.11 ± 5.73, VEGF: 124.8 ± 18.03 vs. 205.9 ± 19.91) in the experimental group than in the control group (p < 0.05). The DCR and KPS of the patients in the experimental group were significantly higher (DCR: 62.50% vs. 40.00%; KPS: 83.25 ± 1.15 vs. 76.25 ± 1.17) than in the control group (p < 0.05). In survival analysis, patients with control group had shorter OS than the experimental group. (median 5.65 vs. 6.50 months; hazard ratio [HR], 1.63 [95% confidence interval (CI) 1.02–2.60], p = 0.0396). Conclusion: The application of low-dose apatinib plus deep hyperthermia for patients with HER-2 negative gastric cancer who failed second-line treatment should be a promising option.
C1 [Han, Guohu] Dushu Lake Hospital Affiliated to Soochow University, Department of OncologySuzhou, Jiangsu, China.
[Sun, Changchun] The Seventh Affiliated Hospital of Yangzhou University, Jingjiang People’s Hospital, Department of OncologyJingjiang, Jiangsu, China.
[Cui, Lihua] The Seventh Affiliated Hospital of Yangzhou University, Jingjiang People’s Hospital, Department of OncologyJingjiang, Jiangsu, China.
[Huang, Yufeng] The Seventh Affiliated Hospital of Yangzhou University, Jingjiang People’s Hospital, Department of OncologyJingjiang, Jiangsu, China.
[Yu, Lijiang] The Seventh Affiliated Hospital of Yangzhou University, Jingjiang People’s Hospital, Department of OncologyJingjiang, Jiangsu, China.
[Liu, Shenzha] The Seventh Affiliated Hospital of Yangzhou University, Jingjiang People’s Hospital, Department of OncologyJingjiang, Jiangsu, China.
[Tao, Min] Dushu Lake Hospital Affiliated to Soochow University, Department of OncologySuzhou, Jiangsu, China.
RP Tao, M (reprint author), Dushu Lake Hospital Affiliated to Soochow University, Department of Oncology, Suzhou, China.
EM taomin@suda.edu.cn
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611114
EP 1611121
DI 10.3389/pore.2023.1611114
PG 8
ER
PT J
AU Gao, Sh
Wei, G
Hao, Y
AF Gao, Shan
Wei, Guanjing
Hao, Yanrong
TI Vitiligo-like lesions induced by cyclin-dependent kinase 4/ 6 inhibitor Palbociclib: a case report and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE breast cancer; CDK4/6 inhibitors; Palbociclib; adverse events; vitiligo-like lesions
ID breast cancer; CDK4/6 inhibitors; Palbociclib; adverse events; vitiligo-like lesions
AB Endocrine therapy has played an essential role in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer. With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2− advanced breast cancer has been greatly improved. Their adverse reactions also need more attention in response to the climbing number of CDK4/6 inhibitors. The common side effects of CDK4/6 inhibitors were hematological toxicity, diarrhea, and liver function damage. Skin toxicity related to CDK4/ 6 inhibitors was rare. We describe herein our preliminary observation of one HR+HER2− advanced metastatic breast cancer patient diagnosed with vitiligolike lesions after 10 months of taking Palbociclib. Hoping to share our experience to increase the clinician awareness of this unusual adverse and contribute to the information in the literature.
C1 [Gao, Shan] People’s Hospital of Guangxi Zhuang Autonomous Region, Clinical Oncology Center, Medical Oncology Division 1Nanning, China.
[Wei, Guanjing] People’s Hospital of Guangxi Zhuang Autonomous Region, Department of Dermatology and VenereologyNanning, China.
[Hao, Yanrong] People’s Hospital of Guangxi Zhuang Autonomous Region, Clinical Oncology Center, Medical Oncology Division 1Nanning, China.
RP Wei, G (reprint author), People’s Hospital of Guangxi Zhuang Autonomous Region, Department of Dermatology and Venereology, Nanning, China.
EM 641634540@qq.com
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Romagnuolo M, Alberti VS, Riva D, Barberi F, Moltrasio C. Vitiligo-like lesions induced by cyclin-dependent kinase 4/6 inhibitor palbociclib. Int J Dermatol, 2023, 62:e98–e100., DOI 10.1111/ijd.16356
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611115
EP 1611119
DI 10.3389/pore.2023.1611115
PG 5
ER
PT J
TI Fibroblast activation protein-α expression in fibroblasts is common in the tumor microenvironment of colorectal cancer and may serve as a therapeutic target
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; tumor microenvironment; cancer-associated fibroblasts; fibroblastactivation protein; radioligand therapy
ID colorectal cancer; tumor microenvironment; cancer-associated fibroblasts; fibroblastactivation protein; radioligand therapy
AB Background: Colorectal cancer (CRC) is still one of the leading causes of cancer death worldwide, emphasizing the need for further diagnostic and therapeutic approaches. Cancer invasion and metastasis are affected by the tumor microenvironment (TME), with cancer-associated fibroblasts (CAF) being the predominant cellular component. An important marker for CAF is fibroblast activation protein-α (FAP) which has been evaluated as therapeutic target for, e.g., radioligand therapy. The aim of this study was to examine CRC regarding the FAP expression as a candidate for targeted therapy. Methods: 67 CRC, 24 adenomas, 18 tissue samples of inflammation sites and 28 non-neoplastic, non-inflammatory tissue samples of colonic mucosa were evaluated for immunohistochemical FAP expression of CAF in tissue microarrays. The results were correlated with clinicopathological data, tumor biology and concurrent expression of additional immunohistochemical parameters. Results: 53/67 (79%) CRC and 6/18 (33%) inflammatory tissue specimens showed expression of FAP. However, FAP was only present in 1/24 (4%) adenomas and absent in normal mucosa (0/28). Thus, FAP expression in CRC was significantly higher than in the other investigated groups. Within the CRC cohort, expression of FAP did not correlate with tumor stage, grading or the MSI status. However, it was observed that tumors exhibiting high immunohistochemical expression of Ki-67, CD3, p53, and β-Catenin showed a significantly higher incidence of FAP expression. Conclusion: In the crosstalk between tumor cells and TME, CAF play a key role in carcinogenesis and metastatic spread. Expression of FAP was detectable in the majority of CRC but nearly absent in precursor lesions and non-neoplastic, non-inflammatory tissue. This finding indicates that FAP has the potential to emerge as a target for new diagnostic and therapeutic concepts in CRC. Additionally, the association between FAP expression and other immunohistochemical parameters displays the interaction between different components of the TME and demands further investigation.
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Lindner T, Altmann A, Kramer S, Kleist C, Loktev A, Kratochwil C, et al. Design and development of, 99m)Tc-labeled FAPI tracers for SPECT imaging and, 188)Re therapy. J Nucl Med, 2020, 61(10):1507–13., DOI 10.2967/jnumed.119. 239731
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611163
EP 1611171
DI 10.3389/pore.2023.1611163
PG 9
ER
PT J
AU Rabindran, B
Corben, A
AF Rabindran, Beryl
Corben, D. Adriana
TI Wide-field optical coherence tomography for microstructural analysis of key tissue types: a proof-of-concept evaluation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE histopathology; breast-conserving surgery; histology; optical coherence tomography; intraoperative margin assessment
ID histopathology; breast-conserving surgery; histology; optical coherence tomography; intraoperative margin assessment
AB Introduction: The presence of positive margins following tumor resection is a frequent cause of re-excision surgery. Nondestructive, real-time intraoperative histopathological imaging methods may improve margin status assessment at the time of surgery; optical coherence tomography (OCT) has been identified as a potential solution but has not been tested with the most common tissue types in surgical oncology using a single, standardized platform. Methods: This was a proof-of-concept evaluation of a novel device that employs wide-field OCT (WF-OCT; OTIS 2.0 System) to image tissue specimens. Various cadaveric tissues were obtained from a single autopsy and were imaged with WF-OCT then processed for permanent histology. The quality and resolution of the WF-OCT images were evaluated and compared to histology and with images in previous literature. Results: A total of 30 specimens were collected and tissue-specific microarchitecture consistent with previous literature were identified on both WF-OCT images and histology slides for all specimens, and corresponding sections were correlated. Application of vacuum pressure during scanning did not affect specimen integrity. On average, specimens were scanned at a speed of 10.3 s/cm2 with approximately three features observed per tissue type. Conclusion: The WF-OCT images captured in this study displayed the key features of the most common human tissue types encountered in surgical oncology with utility comparable to histology, confirming the utility of an FDAcleared imaging platform. With further study, WF-OCT may have the potential to bridge the gap between the immediate information needs of the operating room and the longer timeline inherent to histology workflow.
C1 [Rabindran, Beryl] Perimeter Medical Imaging AIToronto, ON, Canada.
[Corben, D. Adriana] Icahn School of Medicine at Mount SinaiNew York, NY, USA.
RP Rabindran, B (reprint author), Perimeter Medical Imaging AI, Toronto, Canada.
EM baugustine@perimetermed.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611167
EP 1611176
DI 10.3389/pore.2023.1611167
PG 10
ER
PT J
AU Danos, K
Horvath, A
Halasz, J
Tamas, L
Polony, G
AF Danos, Kornel
Horvath, Angela
Halasz, Judit
Tamas, Laszlo
Polony, Gabor
TI Patient delay and its clinical significance among head and neck cancer patients in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE survival; diagnosis; head and neck cancer; patient delay; symptom
ID survival; diagnosis; head and neck cancer; patient delay; symptom
AB Introduction: Head and neck cancers represent a major health problem in Hungary. With their high incidence and mortality rates, Hungary is one of the world leaders in these indicators. The length of patient delay, defined as time from onset of symptoms to first medical consultation, is unknown in Hungarian patients with head and neck cancer. We aimed to use a representative sample of the Hungarian head and neck cancer patient population to determine patient delay according to disease localization and stage and to identify correlations with other clinical parameters. Methods: In our retrospective study, we reviewed patient documentation. For the inclusion, the patients had to be diagnosed with malignant tumors of the oral cavity, oropharynx, hypopharynx or larynx at the Department Head and Neck Surgery of Semmelweis University between 2012 and 2017. Results: We identified 236 patientswho met the inclusion criteria. The median delay was 9.5weeks (range0–209 weeks) and the mean delay of patientswas 17.57weeks (SD 23.67). There was a significant difference in patient delay data by location. Among glottic cancers, the mostcommondiagnosiswas an early stage (67%), comparedwith other localizations, including most commonly the oropharynx (81%) and hypopharynx (80%), where a locoregionally advanced stage was more frequent. Discussion: Compared to data from different countries, the delay of Hungarian patients with head and neck cancer is significantly longer, which may contribute to the high mortality in Hungary. Screening and patient education in high-risk groups could contribute to earlier diagnosis and thus improve prognosis.
C1 [Danos, Kornel] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Horvath, Angela] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Halasz, Judit] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tamas, Laszlo] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
[Polony, Gabor] Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck SurgeryBudapest, Hungary.
RP Horvath, A (reprint author), Semmelweis University, Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Budapest, Hungary.
EM horvathangela11@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611206
EP 1611215
DI 10.3389/pore.2023.1611206
PG 10
ER
PT J
AU Jiang, W
Hu, K
Liu, X
Gao, J
Zhu, L
AF Jiang, Wenru
Hu, Kangyao
Liu, Xiaofei
Gao, Jili
Zhu, Liping
TI Single-cell transcriptome analysis reveals the clinical implications of myeloid-derived suppressor cells in head and neck squamous cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE head and neck squamous cell carcinoma; myeloid-derived suppressor cell; single cell RNA sequencing (scRNA-seq); prognosis; immunotherapeutic
ID head and neck squamous cell carcinoma; myeloid-derived suppressor cell; single cell RNA sequencing (scRNA-seq); prognosis; immunotherapeutic
AB Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor that arises in the epithelium of the head and neck regions. Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell populations, which play a powerful role in inhibiting antitumor immune response. Herein, we employed a single-cell RNA sequencing (scRNA-seq) dataset to dissect the heterogeneity of myeloid cells. We found that SPP1+ tumor-associated macrophages (TAMs) and MDSCs were the most abundant myeloid cells in the microenvironment. By cell cluster deconvolution from bulk RNA-seq datasets of larger patient groups, we observed that highly-infiltrated MDSC was a poor prognostic marker for patients’ overall survival (OS) probabilities. To better apply the MDSC OS prediction values, we identified a set of six MDSC-related genes (ALDOA, CD52, FTH1, RTN4, SLC2A3, and TNFAIP6) as the prognostic signature. In both training and test cohorts, MDSC-related prognostic signature showed a promising value for predicting patients’ prognosis outcomes. Further parsing the ligand-receptor pairs of intercellular communications by CellChat, we found that MDSCs could frequently interact with cytotoxic CD8+ T cells, SPP1+ TAMs, and endothelial cells. These interactions likely contributed to the establishment of an immunosuppressive microenvironment and the promotion of tumor angiogenesis. Our findings suggest that targeting MDSCs may serve as an alternative and promising target for the immunotherapy of HNSC.
C1 [Jiang, Wenru] Harbin First Hospital, Department of Implant and ProsthodonticsHarbin, China.
[Hu, Kangyao] Harbin First Hospital, Department of Implant and ProsthodonticsHarbin, China.
[Liu, Xiaofei] Harbin First Hospital, Department of Implant and ProsthodonticsHarbin, China.
[Gao, Jili] Harbin First Hospital, Department of Implant and ProsthodonticsHarbin, China.
[Zhu, Liping] Harbin First Hospital, Department of Implant and ProsthodonticsHarbin, China.
RP Zhu, L (reprint author), Harbin First Hospital, Department of Implant and Prosthodontics, Harbin, China.
EM 1920636476@qq.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611210
EP 1611219
DI 10.3389/pore.2023.1611210
PG 10
ER
PT J
AU Chai, J
Liu, X
Hu, X
Wang, Ch
AF Chai, Jie
Liu, Xiangli
Hu, Xinju
Wang, Chunfang
TI Correlation analysis of circulating tumor cells and Claudin-4 in breast cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; circulating tumor cells; tight junction protein; claudin-4; molecular subtype
ID breast cancer; circulating tumor cells; tight junction protein; claudin-4; molecular subtype
AB Objective: We aimed to explore the relationship between peripheral blood circulating tumor cells (CTCs) and the expression of Claudin-4 in patients with breast cancer, and further explore the potential impact on clinical prognosis and risk assessment. Methods: We classified and enumerated circulating tumor cells in the blood of breast cancer patients by CTC-enriched in situ hybridization and the detection of Claudin-4 expression by immunohistochemistry. We carried out an analysis of the correlation between the two and the comparison of their impact on clinical parameters and prognosis. Results: There were 38 patients with a low expression of Claudin-4 and 27 patients with a high expression of Claudin-4. Compared with Claudin-4 low-expression patients, the number of CTCs was higher in patients with high Claudin-4 expression (11.7 vs. 7.4, p < 0.001). High Claudin-4 expression was associated with a lower count of epithelial CTCs (E-CTCs) (3.4 vs. 5.0, p = 0.033), higher counts of mesenchymal CTCs (M-CTC) (4.4 vs. 1.1, p < 0.001), and epithelial/mesenchymal CTCs (E/M-CTCs) (4.0 vs. 3.5, p = 0.021). The intensity of Claudin-4 was positively correlated with CTC (rs = 0.43, p = 0.001). Multivariate COX regression analysis showed that CTC counts (HR = 1.3, p < 0.001), Claudin-4 (HR = 4.6, p = 0.008), and Lymphatic metastasis (HR = 12.9, p = 0.001) were independent factors for poor prognosis. COX regression of CTC classification showed that epithelial/mesenchymal CTCs (E/M-CTC) (HR = 1.9, p = 0.001) and mesenchymal CTCs (M-CTC) (HR = 1.5, p = 0.001) were independent influencing factors of adverse reactions in breast cancer patients. Conclusion: The number of CTC in breast cancer is positively correlated with the expression of Claudin-4. High CTC counts and a high proportion of M-CTCs correlated with Claudin-4 expression. CTC counts and Claudin-4 expression were independent predictors of poor prognosis in breast cancer patients.
C1 [Chai, Jie] The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Pathology DepartmentZhengzhou, China.
[Liu, Xiangli] The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Pathology DepartmentZhengzhou, China.
[Hu, Xinju] The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Pathology DepartmentZhengzhou, China.
[Wang, Chunfang] The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Breast SurgeryZhengzhou, China.
RP Wang, Ch (reprint author), The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Breast Surgery, Zhengzhou, China.
EM asangna009@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611224
EP 1611232
DI 10.3389/pore.2023.1611224
PG 9
ER
PT J
AU Villanueva-Cotrina, F
Velarde, J
Rodriguez, R
Bonilla, A
Laura, M
Saavedra, T
Portillo-Alvarez, D
Bustamante, Y
Fernandez, C
Galvez-Nino, M
AF Villanueva-Cotrina, Freddy
Velarde, Juan
Rodriguez, Ricardo
Bonilla, Alejandra
Laura, Marco
Saavedra, Tania
Portillo-Alvarez, Diana
Bustamante, Yovel
Fernandez, Cesar
Galvez-Nino, Marco
TI Active cancer as the main predictor of mortality for COVID-19 in oncology patients in a specialized center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE SARS-CoV-2; imaging study; biomarkers; death prognosis; active cancer
ID SARS-CoV-2; imaging study; biomarkers; death prognosis; active cancer
AB Introduction: The role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. Objective: To identify potential predictors of mortality of COVID-19 in cancer patients. Materials and methods: A retrospective and cross-sectional study was carried out in patients with clinical suspicion of COVID-19 who were confirmed for COVID-19 diagnosis by RT-PCR testing at the National Institute of Neoplastic Diseases between April and December 2020. Demographic, clinical, laboratory and radiological data were analyzed. Statistical analyses included area under the curve and univariate and multivariate logistic regression analyses. Results: A total of 226 patients had clinical suspicion ofCOVID-19, the diagnosiswas confirmed in 177 (78.3%), and 70/177 (39.5%) died. Age, active cancer, leukocyte count ≥12.8× 109/L, urea ≥7.4mmol/L, ferritin ≥1,640, lactate ≥2.0 mmol/L, and lung involvement ≥35% were found to be independent predictors of COVID-19mortality. Conclusion: Active cancer represents the main prognosis factor of death, while the role of cancer stage and type is unclear. Chest CT is a useful tool in the prognosis of death from COVID-19 in cancer patients. It is a challenge to establish the prognostic utility of laboratory markers as their altered values it could have either oncological or pandemic origins.
C1 [Villanueva-Cotrina, Freddy] Instituto Nacional de Enfermedades Neoplasicas, Department of PathologyLima, Peru.
[Velarde, Juan] Instituto Nacional de Enfermedades Neoplasicas, Department of Infectious DiseasesLima, Peru.
[Rodriguez, Ricardo] Instituto Nacional de Enfermedades Neoplasicas, Department of PathologyLima, Peru.
[Bonilla, Alejandra] Instituto Nacional de Enfermedades Neoplasicas, Department of RadiodiagnosisLima, Peru.
[Laura, Marco] Instituto Nacional de Enfermedades Neoplasicas, Department of RadiodiagnosisLima, Peru.
[Saavedra, Tania] Instituto Nacional de Enfermedades Neoplasicas, Department of Critical Care MedicineLima, Peru.
[Portillo-Alvarez, Diana] Instituto Nacional de Enfermedades Neoplasicas, Department of Infectious DiseasesLima, Peru.
[Bustamante, Yovel] Instituto Nacional de Enfermedades Neoplasicas, Department of PathologyLima, Peru.
[Fernandez, Cesar] Instituto Nacional de Enfermedades Neoplasicas, Department of PathologyLima, Peru.
[Galvez-Nino, Marco] Universidad Privada San Juan Bautista, Professional School of Human MedicineLima, Peru.
RP Villanueva-Cotrina, F (reprint author), Instituto Nacional de Enfermedades Neoplasicas, Department of Pathology, Lima, Peru.
EM freddyvillanue@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611236
EP 1611247
DI 10.3389/pore.2023.1611236
PG 12
ER
PT J
AU Cazzaniga, M
Zonzini, BG
Pierro, DF
Palazzi, MCh
Cardinali, M
Bertuccioli, A
AF Cazzaniga, Massimiliano
Zonzini, Bruno Giordano
Pierro, Di Francesco
Palazzi, Maria Chiara
Cardinali, Marco
Bertuccioli, Alexander
TI Influence of the microbiota on the effectiveness and toxicity of oncological therapies, with a focus on chemotherapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE microbiota; chemotherapy; oncology; toxicity; microbiome
ID microbiota; chemotherapy; oncology; toxicity; microbiome
AB Recent studies have highlighted a possible correlation between microbiota composition and the pathogenesis of various oncological diseases. Also, many bacterial groups are now directly or indirectly associated with the capability of stimulating or inhibiting carcinogenic pathways. However, little is known about the importance and impact of microbiota patterns related to the efficacy and toxicity of cancer treatments. We have recently begun to understand how oncological therapies and the microbiota are closely interconnected and could influence each other. Chemotherapy effectiveness, for example, appears to be strongly influenced by the presence of some microorganisms capable of modulating the pharmacokinetics and pharmacodynamics of the compounds used, thus varying the real response and therefore the efficacy of the oncological treatment. Similarly, chemotherapeutic agents can modulate the microbiota with variations that could facilitate or avoid the onset of important side effects. This finding has or could have considerable relevance as it is possible that our ability to modulate and modify the microbial structure before, during, and after treatment could influence all the clinical parameters related to pharmacological treatments and, eventually, the prognosis of the disease.
C1 [Cazzaniga, Massimiliano] Velleja Research, Scientific and Research DepartmentMilano, Italy.
[Zonzini, Bruno Giordano] University of Urbino Carlo Bo, Department of Biomolecular SciencesUrbino, Italy.
[Pierro, Di Francesco] Velleja Research, Scientific and Research DepartmentMilano, Italy.
[Palazzi, Maria Chiara] Associazione Italiana Fitness e MedicinaRavenna, Italy.
[Cardinali, Marco] Azienda Unita Sanitaria Locale Romagna, Infermi Hospital, Department of Internal MedicineRimini, Italy.
[Bertuccioli, Alexander] University of Urbino Carlo Bo, Department of Biomolecular SciencesUrbino, Italy.
RP Bertuccioli, A (reprint author), University of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, Italy.
EM alexander.bertuccioli@uniurb.it
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611300
EP 1611308
DI 10.3389/pore.2023.1611300
PG 9
ER
PT J
AU Gyulai, M
Harko, T
Fabian, K
Karsko, L
Agocs, L
Szigeti, B
Fillinger, J
Szallasi, Z
Pipek, O
Moldvay, J
AF Gyulai, Marton
Harko, Tunde
Fabian, Katalin
Karsko, Luca
Agocs, Laszlo
Szigeti, Balazs
Fillinger, Janos
Szallasi, Zoltan
Pipek, Orsolya
Moldvay, Judit
TI Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE adenoid cystic carcinoma; mucoepidermoid carcinoma; rare lung tumors; claudin expression; immunohistochemistry
ID adenoid cystic carcinoma; mucoepidermoid carcinoma; rare lung tumors; claudin expression; immunohistochemistry
AB Background: Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. Methods: 35 rare lung cancers including pathologically confirmed 12 adenoid cystic carcinomas (ACCs) and 23 mucoepidermoid carcinomas (MECs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and CLDN1, -2, -3, -4, -5, -7, and -18 protein expressions were analyzed. The levels of immunopositivity were determined with H-score. Certain pathological characteristics of ACC and MEC samples (tumor grade, presence of necrosis, presence of blood vessel infiltration, and degree of lymphoid infiltration) were also analyzed. Results: CLDN overexpression was observed in both tumor types, especially in CLDN2, -7, and -18 IHC. Markedly different patterns of CLDN expression were found for ACC and MEC tumors, especially for CLDN1, -2, -4, and -7, although none of these trends remained significant after correction for multiple testing. Positive correlations between expressions of CLDN2 and -5, CLDN3 and -4, and CLDN5 and -18 were also demonstrated. Tumors of never-smokers presented lower levels of CLDN18 than tumors of current smokers (p-value: 0.003). Conclusion: This is the first study to comprehensively describe the expression of different CLDNs in lung ACC and MEC. Overexpression of certain CLDNs may pave the way for targeted anti-claudin therapy in these rare histological subtypes of lung cancer.
C1 [Gyulai, Marton] County Hospital of PulmonologyTorokbalint, Hungary.
[Harko, Tunde] Orszagos Koranyi Pulmonologiai Intezet, Patologiai OsztalyBudapest, Hungary.
[Fabian, Katalin] Municipal Hospital, Del-Pest, Department of PathologyBudapest, Hungary.
[Karsko, Luca] Orszagos Koranyi Tbc es Pulmonologiai Intezet, MellkassebeszetBudapest, Hungary.
[Agocs, Laszlo] Orszagos Koranyi Tbc es Pulmonologiai Intezet, MellkassebeszetBudapest, Hungary.
[Szigeti, Balazs] Orszagos Koranyi Pulmonologiai Intezet, Patologiai OsztalyBudapest, Hungary.
[Fillinger, Janos] Orszagos Koranyi Pulmonologiai Intezet, Patologiai OsztalyBudapest, Hungary.
[Szallasi, Zoltan] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Pipek, Orsolya] Eotvos Lorand University, Department of Physics of Complex SystemsBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute of Pulmonology, Semmelweis University, Ist Department of PulmonologyBudapest, Hungary.
RP Moldvay, J (reprint author), National Koranyi Institute of Pulmonology, Semmelweis University, Ist Department of Pulmonology, Budapest, Hungary.
EM drmoldvay@hotmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611328
EP 1611337
DI 10.3389/pore.2023.1611328
PG 10
ER
PT J
AU Ni, H
Ding, X
Wu, Sh
Jin, X
AF Ni, Hua
Ding, Xinjia
Wu, Shikai
Jin, Xuan
TI Case report: Clinical experience of treating pembrolizumab-induced systemic capillary leak syndrome (SCLS) in one patient with metastatic gastroesophageal junction squamous cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE immune checkpoint inhibitor; pembrolizumab; adverse effect; systemic capillary leak syndrome; SCLS
ID immune checkpoint inhibitor; pembrolizumab; adverse effect; systemic capillary leak syndrome; SCLS
AB Systemic capillary leak syndrome (SCLS) is a rare and complex adverse effect of immune checkpoint inhibitors (ICIs). The diagnosis of drug-induced SCLS is based on diffuse infusions of exudative fluid into the interstitial areas and the exclusion of other causes. The best management of ICIs-induced SCLS is not settled, though proper supportive care and corticosteroids were commonly applied as the first-line treatment. In our patient with advanced gastroesophageal junction squamous cell carcinoma, although ICIs-induced SCLS was successfully controlled with corticosteroids, the patient soon experienced cancer progress and died of pulmonary infections. Based on our experience and the reported cases by other hospitals, different stages of SCLS might respond differently to the same treatment. Therefore, a grading of ICIs-induced SCLS might help to stratify the patient for different treatment strategies. Besides, corticosteroids-sensitive patients, though waived from deadly SCLS, might be at higher risk of cancer progress and subsequent infections due to the application of corticosteroids. Considering that the inflammatory factors should be closely involved in the development of ICIsinduced SCLS, targeted therapy against the driver inflammatory cytokine might offer treatment regimens that are more effective and safer.
C1 [Ni, Hua] Peking University First Hospital, Department of Medical OncologyBeijing, China.
[Ding, Xinjia] Peking University First Hospital, Department of Medical OncologyBeijing, China.
[Wu, Shikai] Peking University First Hospital, Department of Medical OncologyBeijing, China.
[Jin, Xuan] Peking University First Hospital, Department of Medical OncologyBeijing, China.
RP Jin, X (reprint author), Peking University First Hospital, Department of Medical Oncology, Beijing, China.
EM jinxuanbdyy@outlook.com
CR Clarkson B, Thompson D, Horwith M, Luckey EH. Cyclical edema and shock due to increased capillary permeability. Am J Med, 1960, 29:193–216., DOI 10.1016/ 0002-9343(60)90018-8
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Izzedine H, Mathian A, Amoura Z, Ng JH, Jhaveri KD. Anticancer Drug- Induced capillary leak syndrome. Kidney Int Rep, 2022, 7(5):945–53., DOI 10.1016/j. ekir.2022.02.014
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Pineton de Chambrun M, Gousseff M, Mauhin W, Lega JC, Lambert M, Riviere S, et al. Intravenous immunoglobulins improve survival in monoclonal Gammopathy-Associated systemic Capillary-Leak syndrome. Am J Med, 2017, 130(10):1219 e19–1219.e27., DOI 10.1016/j.amjmed.2017.05.023
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611330
EP 1611333
DI 10.3389/pore.2023.1611330
PG 4
ER
PT J
AU Tie, W
Ma, T
Yi, Z
Liu, J
Li, Y
Bai, J
Li, L
Zhang, L
AF Tie, Wenting
Ma, Tao
Yi, Zhigang
Liu, Jia
Li, Yanhong
Bai, Jun
Li, Lijuan
Zhang, Liansheng
TI Obesity as a risk factor for multiple myeloma: insight on the role of adipokines
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE multiple myeloma; adipokine; obesity; adiponectin; leptin
ID multiple myeloma; adipokine; obesity; adiponectin; leptin
AB Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are contributed to the etiology of MM. Notably, studies have shown that obesity increases the risk of MM and worsens outcomes for MM patients. Adipokines play an important role in mediating the close association between MM and metabolic derangements. In this review, we summarize the epidemiologic studies to show that the risk of MM is increased in obese. Accumulating clinical evidence suggests that adipokines could display a correlation with MM. In vitro and in vivo studies have shown that adipokines are linked to MM, including roles in the biological behavior of MM cells, cancer-associated bone loss, the progression of MM, and drug resistance. Current and potential therapeutic strategies targeted to adipokines are discussed, proposing that adipokines can guide early patient diagnosis and treatment.
C1 [Tie, Wenting] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Ma, Tao] The Affiliated Hospital of Southwest Medical University, Department of HematologyLuzhou, China.
[Yi, Zhigang] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Liu, Jia] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Li, Yanhong] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Bai, Jun] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Li, Lijuan] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
[Zhang, Liansheng] Lanzhou University Second Hospital, Department of HematologyLanzhou, China.
RP Zhang, L (reprint author), Lanzhou University Second Hospital, Department of Hematology, Lanzhou, China.
EM doctorzhanglsh@sina.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611338
EP 1611347
DI 10.3389/pore.2023.1611338
PG 10
ER
PT J
TI A unique case of AH-dominant type nodular pulmonary amyloidosis presenting as a spontaneous pneumothorax: a case report and review of the literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE amyloidosis; nodular pulmonary amyloidosis; amyloidoma; AH amyloidosis; pneumothorax
ID amyloidosis; nodular pulmonary amyloidosis; amyloidoma; AH amyloidosis; pneumothorax
AB Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
CR Milani P, Basset M, Russo F, Foli A, Palladini G, Merlini G. The lung in amyloidosis. Eur Respir Rev, 2017, 26(145):170046., DOI 10.1183/16000617.0046- 2017
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Rajagopala S, Singh N, Gupta K, Gupta D. Pulmonary amyloidosis in sjogren’s syndrome: a case report and systematic review of the literature. Respirology, 2010, 15(5):860–6., DOI 10.1111/j.1440-1843.2010.01772.x
Kruczak K, Duplaga M, Sanak M, Papla B, Soja J, Nizankowska-Mogilnicka E, et al. Transthyretin amyloidosis with pulmonary involvement in a patient with monoclonal gammapathy. Pneumonol Alergol Pol, 2013, 81(6):537–41., DOI 10. 5603/arm.35995
Miyamoto T, Kobayashi T, Makiyama M, Kitada S, Fujishima M, Hagari Y, et al. Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction. J Clin Pathol, 1999, 52(6): 464–7., DOI 10.1136/jcp.52.6.464
Davis CJ, Butchart EG, Gibbs AR. Nodular pulmonary amyloidosis occurring in association with pulmonary lymphoma. Thorax, 1991, 46(3):217–8., DOI 10.1136/ thx.46.3.217
Roden AC, Aubry MC, Zhang K, Brady JO, Levin D, Dogan A, et al. Nodular senile pulmonary amyloidosis: a unique case confirmed by immunohistochemistry, mass spectrometry, and genetic study. Hum Pathol, 2010, 41(7):1040–5., DOI 10. 1016/j.humpath.2009.11.019
Kinoshita Y, Ikeda T, Miyamura T, Ueda Y, Yoshida Y, Ueda M, et al. Nodular pulmonary amyloidosis associated with sjogren’s syndrome. Intern Med, 2022, 61(6):877–81., DOI 10.2169/internalmedicine.8169-21
Grogg KL, Aubry MC, Vrana JA, Theis JD, Dogan A. Nodular pulmonary amyloidosis is characterized by localized immunoglobulin deposition and is frequently associated with an indolent B-cell lymphoproliferative disorder. Am J Surg Pathol, 2013, 37(3):406–12., DOI 10.1097/PAS.0b013e318272fe19
Gorospe Sarasua L, Munoz-Molina GM, Arrieta P. Loculated secondary spontaneous pneumothorax: A very rare complication of nodular pulmonary amyloidosis. Arch Bronconeumol, 2016, 52(10):530., DOI 10.1016/j.arbres.2015.
012 11. Ikeda S, Takabayashi Y, Maejima Y, Tachibana N, Ehara T, Nezu A, et al. Nodular lung disease with five year survival and unilateral pleural effusion in AL amyloidosis. Amyloid, 1999, 6(4):292–6., DOI 10.3109/13506129909007343
Calatayud J, Candelas G, Gomez A, Morado C, Trancho FH. Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis. Clin Rheumatol, 2007, 26(10):1797–8., DOI 10.1007/s10067-007-0552-y
Moscatelli B, Capoccetta GB, Anselmi P, Di Girolamo M, Campagna D. Kappa L-chain primary nodular lung amyloidosis: a case report. Amyloid, 2011, 18(1):121–3., DOI 10.3109/13506129.2011.574354045
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Kaplan B, Martin BM, Boykov O, Gal R, Pras M, Shechtman I, et al. Codeposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis. Virchows Arch, 2005, 447(4):756–61., DOI 10.1007/s00428- 005-0009-0
Seguchi T, Kyoraku Y, Saita K, Ihi T, Nagai M, Akiyama Y, et al. Human T-cell lymphotropic virus type I, HTLV-1, associated myelopathy and sjogren’s syndrome representing pulmonary nodular amyloidosis and multiple bullae: report of an autopsy case. Virchows Arch, 2006, 448(6):874–6., DOI 10.1007/ s00428-005-0028-x
Wieker K, Rocken C, Koenigsmann M, Roessner A, Franke A. Pulmonary low-grade MALT-lymphoma associated with localized pulmonary amyloidosis. A case report. Amyloid, 2002, 9(3):190–3., DOI 10.3109/13506120209114821
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Kobayashi H, Matsuoka R, Kitamura S, Tsunoda N, Saito K. Sjogren’s syndrome with multiple bullae and pulmonary nodular amyloidosis. Chest, 1988, 94(2):438–40., DOI 10.1378/chest.94.2.438
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611390
EP 1611399
DI 10.3389/pore.2023.1611390
PG 10
ER
PT J
AU Wang, Q
Liang, Q
Wei, W
Niu, W
Liang, Ch
Wang, X
Wang, X
Pan, H
AF Wang, Qiang
Liang, Qiujin
Wei, Wuting
Niu, Wenhao
Liang, Chong
Wang, Xiaoliang
Wang, Xiaoxuan
Pan, Hao
TI Concordance analysis of cerebrospinal fluid with the tumor tissue for integrated diagnosis in gliomas based on next-generation sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE cerebrospinal fluid; glioma; circulating tumor DNA; integrated diagnosis; IDH1 R132C
ID cerebrospinal fluid; glioma; circulating tumor DNA; integrated diagnosis; IDH1 R132C
AB Purpose: The driver mutations of gliomas have been identified in cerebrospinal fluid (CSF). Here we compared the concordance between CSF and tumor tissue for integrated diagnosis in gliomas using next-generation sequencing (NGS) to evaluate the feasibility of CSF detection in gliomas. Patients and methods: 27 paired CSF/tumor tissues of glioma patients were sequenced by a customized gene panel based on NGS. All CSF samples were collected through lumbar puncture before surgery. Integrated diagnosis was made by analysis of histology and tumor DNA molecular pathology according to the 2021 WHO classification of the central nervous system tumors. Results: A total of 24 patients had detectable circulating tumor DNA (ctDNA) and 22 had at least one somatic mutation or chromosome alteration in CSF. The ctDNA levels varied significantly across different ages, Ki-67 index, magnetic resonance imaging signal and glioma subtypes (p < 0.05). The concordance between integrated ctDNA diagnosis and the final diagnosis came up to 91.6% (Kappa, 0.800). We reclassified the clinical diagnosis of 3 patients based on the results of CSF ctDNA sequencing, and 4 patients were reassessed depending on tumor DNA. Interestingly, a rare IDH1 R132C was identified in CSF ctDNA, but not in the corresponding tumor sample. Conclusion: This study demonstrates a high concordance between integrated ctDNA diagnosis and the final diagnosis of gliomas, highlighting the practicability of NGS based detection of mutations of CSF in assisting integrated diagnosis of gliomas, especially glioblastoma.
C1 [Wang, Qiang] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Liang, Qiujin] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Neurology and Oncology Drug DevelopmentNanjing, China.
[Wei, Wuting] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Niu, Wenhao] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Liang, Chong] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Wang, Xiaoliang] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
[Wang, Xiaoxuan] Jiangsu Simcere Diagnostics Co., Ltd., State Key Laboratory of Neurology and Oncology Drug DevelopmentNanjing, China.
[Pan, Hao] Nanjing University, School of Medicine, Jinling Hospital, Department of NeurosurgeryNanjing, China.
RP Pan, H (reprint author), Nanjing University, School of Medicine, Jinling Hospital, Department of Neurosurgery, Nanjing, China.
EM Panhao_nz@163.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611391
EP 1611401
DI 10.3389/pore.2023.1611391
PG 11
ER
PT J
AU Klemm, E
Nowak, A
AF Klemm, Eckart
Nowak, Andreas
TI Commentary: Percutaneous tracheostomy: comparison of three different methods with respect to tracheal cartilage injury in cadavers—randomized controlled study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Letter
DE tracheostomy; tracheal ring fracture; histology; tracheal stenosis; intensive care unit
ID tracheostomy; tracheal ring fracture; histology; tracheal stenosis; intensive care unit
C1 [Klemm, Eckart] Stadtisches Klinikum Dresden, Department of Otorhinolaryngology, Head and Neck Surgery, Plastic SurgeryDresden, Germany.
[Nowak, Andreas] Stadtisches Klinikum Dresden, Department of Anesthesiology and Intensive Care Medicine, Emergency Medicine and Pain ManagementDresden, Germany.
RP Nowak, A (reprint author), Stadtisches Klinikum Dresden, Department of Anesthesiology and Intensive Care Medicine, Emergency Medicine and Pain Management, Dresden, Germany.
EM andreas.nowak@klinikum-dresden.de
CR Bodis F, Orosz G, Toth JT, Szabo M, Elo LG, Gal J, et al. Percutaneous tracheostomy: comparison of three different methods with respect to tracheal cartilage injury in cadavers-randomized controlled study. Pathol Oncol Res, 2023, 29:1610934., DOI 10.3389/pore.2023.1610934
Klemm E, Nowak A, Haroske G. Histomorphologische Befunde der 2. und
Trachealspange von Tracheotomiepatienten der Intensivmedizin. GMS Curr Posters Otorhinolaryngol Head Neck Surg, 2011, 7:Doc43, DOI 10.3205/ cpo000632 3. Nowak A, Kern P, Koscielny S, Usichenko T, Hahnenkamp K, et al. Feasibility and safety of dilatational tracheotomy using the rigid endoscope: a multicenter study. BMC Anesthesiol, 2017, 17:7., DOI 10.1186/s12871-017- 0301-y
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2023
VL 29
IS 3
BP 1611451
EP 1611452
DI 10.3389/pore.2023.1611451
PG 2
ER
PT J
AU Mai, Y
Feng, L
Liu, Z
Nie, Y
Jiang, Z
Qin, J
AF Mai, Yanxing
Feng, Lei
Liu, Zhenxi
Nie, Yu
Jiang, Zesheng
Qin, Jiasheng
TI Urachus adenocarcinoma mistaken for umbilical incision implant cancer after laparoscopic cholecystectomy: a case report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE urachus adenocarcinoma; laparoscopic cholecystectomy; umbilical incision implant cancer; invasive adenocarcinoma; case report
ID urachus adenocarcinoma; laparoscopic cholecystectomy; umbilical incision implant cancer; invasive adenocarcinoma; case report
AB Umbilical incision implant cancer after LC is rare. Elective cholecystectomy was planned for a 49 years-old female patient with symptomatic gallstones. The patient underwent transumbilical single-port LC after admission to our hospital. Gallbladder specimens were obtained directly through the umbilical puncture hole, and histopathology suggested chronic cholecystitis. Three months after surgery, the patient experienced painful induration in the umbilicus. We initially considered incision scar hyperplasia complicated with pain, and used drugs to treat it conservatively without taking special treatment measures. Six months after LC, the umbilical induration pain affected her quality of life, and the patient requested surgical resection. Preoperative ultrasonography and abdominal computerized tomography (CT) revealed nodular changes around the umbilicus and no abdominal mass. Local resection of the periumbilical mass was performed, and the pathological confirmation was invasive adenocarcinoma. Subsequently, the patient underwent repeat periumbilical mass enlargement resection. Postoperative pathology showed no cancer at the enlarged resection margin, yet the umbilical center pathology showed invasive adenocarcinoma. The excised pathology was sent to the Sun Yat-sen University Cancer Center for consultation because of the rare nature of the findings associated with the case. After consultation, a diagnosis of umbilical urachus adenocarcinoma was confirmed based on pathological morphology, immunohistochemistry, and the specific anatomical location of the tumor. This case report shown that when there is a persistent mass induration in the navel after LC surgery, the possibility of incision tumor should be considered, rather than simply excluding the possibility of a cancer based on a non-cancer medical history.
C1 [Mai, Yanxing] Southern Medical University, Zhujiang Hospital, Department of GeriatricsGuangzhou, China.
[Feng, Lei] Southern Medical University, Zhujiang Hospital, Department of Hepatobiliary Surgery II, General Surgery Center, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative MedicineGuangzhou, China.
[Liu, Zhenxi] Southern Medical University, Zhujiang Hospital, Department of PathologyGuangzhou, China.
[Nie, Yu] Southern Medical University, Zhujiang Hospital, Department of Hepatobiliary Surgery II, General Surgery Center, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative MedicineGuangzhou, China.
[Jiang, Zesheng] Southern Medical University, Zhujiang Hospital, Department of Hepatobiliary Surgery II, General Surgery Center, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative MedicineGuangzhou, China.
[Qin, Jiasheng] Southern Medical University, Zhujiang Hospital, Department of Hepatobiliary Surgery II, General Surgery Center, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative MedicineGuangzhou, China.
RP Qin, J (reprint author), Southern Medical University, Zhujiang Hospital, Department of Hepatobiliary Surgery II, General Surgery Center, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Guangzhou, China.
EM 66707647@qq.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611334
EP 1611341
DI 10.3389/pore.2023.1611334
PG 8
ER
PT J
AU Zhang, C
Jia, Y
Kong, Q
AF Zhang, Caixin
Jia, Yong
Kong, Qingnuan
TI Case report: Squamous cell carcinoma of the prostate-a clinicopathological and genomic sequencing-based investigation
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE squamous cell carcinoma; prostate adenocarcinoma; whole exome sequencing; gene mutation; SCC
ID squamous cell carcinoma; prostate adenocarcinoma; whole exome sequencing; gene mutation; SCC
AB Squamous differentiation of prostate cancer, which accounts for less than 1% of all cases, is typically associated with androgen deprivation treatment (ADT) or radiotherapy. This entity is aggressive and exhibits poor prognosis due to limited response to traditional treatment. However, the underlying molecular mechanisms and etiology are not fully understood. Previous findings suggest that squamous cell differentiation may potentially arise from prostate adenocarcinoma (AC), but further validation is required to confirm this hypothesis. This paper presents a case of advanced prostate cancer with a combined histologic pattern, including keratinizing SCC and AC. The study utilized whole-exome sequencing (WES) data to analyze both subtypes and identified a significant overlap in driver gene mutations between them. This suggests that the two components shared a common origin of clones. These findings emphasize the importance of personalized clinical management for prostate SCC, and specific molecular findings can help optimize treatment strategies.
C1 [Zhang, Caixin] Qingdao Municipal Hospital, Department of PathologyQingdao, China.
[Jia, Yong] Qingdao Municipal Hospital, Department of UrologyQingdao, China.
[Kong, Qingnuan] Qingdao Municipal Hospital, Department of PathologyQingdao, China.
RP Kong, Q (reprint author), Qingdao Municipal Hospital, Department of Pathology, Qingdao, China.
EM nuanyun4621@126.com
CR Dizman N, Salgia M, Ali SM, Wu H, Arvanitis L, Chung JH, et al. Squamous transformation of prostate adenocarcinoma: a report of two cases with genomic profiling. ClinGenitourin Cancer, 2020, 18(3):e289–92., DOI 10.1016/j.clgc.2019.11.020
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Adams EJ, Karthaus WR, Hoover E, Liu D, Gruet A, Zhang Z, et al. FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature, 2019, 571(7765):408–12., DOI 10.1038/s41586-019-1318-9
Teng M, Zhou S, Cai C, Lupien M, He HH. Pioneer of prostate cancer: past, present and the future of FOXA1. Protein Cell, 2021, 12(1):29–38., DOI 10.1007/ s13238-020-00786-8
Parolia A, Cieslik M, Chu SC, Xiao L, Ouchi T, Zhang Y, et al. Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer. Nature, 2019, 571(7765):413–8., DOI 10.1038/s41586-019-1347-4
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Wu X, Li J, Yan T, Ke X, Li X, Zhu Y, et al. HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma. Cancer Cell Int, 2021, 21(1): 393., DOI 10.1186/s12935-021-02093-6
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611343
EP 1611348
DI 10.3389/pore.2023.1611343
PG 6
ER
PT J
AU Almasi, Sz
Nagy,
Krenacs, T
Lantos, T
Zombori, T
Cserni, G
AF Almasi, Szintia
Nagy, Agnes
Krenacs, Tibor
Lantos, Tamas
Zombori, Tamas
Cserni, Gabor
TI The prognostic value of stem cell markers in triple-negative breast cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE immunohistochemistry; prognosis; CD44; ALDH1; stem cell markers; triple-negative breast cancer
ID immunohistochemistry; prognosis; CD44; ALDH1; stem cell markers; triple-negative breast cancer
AB Among the many consecutive theories of cancer, the stem cell theory is currently the most accepted one. Cancer stem cells are located in small niches with specific environment, renew themselves and are believed to be responsible for many recurrences. They can be highlighted with stem cell markers, but often these markers also label tumor cells, and this may represent a phenotypical change associated with prognosis. In this study, we attempted to match tumor outcomes with the expression of the following stem cell markers: ALDH1, AnnexinA1, CD44, CD117, CD166, Nanog and oct-4. Tissue microarray blocks from triple-negative breast cancers were immunostained for the listed markers, and their expression by the majority of tumor cells (diffuse positivity) was correlated with prognosis. Of the 106 tumors investigated, diffuse positivity was seen in 7 (ALDH1), 33 (AnnexinA1), 53 (CD44), 44 (CD117 membranous only), 49 (CD117), 72 (CD166), 19 (Nanog), and 11 (oct-4) cases. With a median follow-up of 83 months, ALDH1 and CD117 expression was associated with DFS, whereas CD44, CD117 and CD166 were associated with OS estimates, based on Kaplan- Meier analyses. In the multivariate Cox proportional hazard models (including the examined markers and clinicopathological data which had a statistical impact in the univariate analysis), the pN category and the lack of ALDH1 expression were independent prognosticators for DFS, and the pN category and diffuse CD44 staining were independent prognosticators for OS. In the multivariate analysis including all of the examined clinicopathological data and markers, only CD117 showed a statistical impact on OS. Wefailed to demonstrate a prognostic impact for most stem cell markers tested in triple-negative breast cancer, but lack of ALDH1 staining and CD44 expression appears as of prognostic value, requiring further examination in independent studies.
C1 [Almasi, Szintia] University of Szeged, Department of PathologySzeged, Hungary.
[Nagy, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Lantos, Tamas] University of Szeged, Department of Medical InformaticsSzeged, Hungary.
[Zombori, Tamas] University of Szeged, Department of PathologySzeged, Hungary.
[Cserni, Gabor] University of Szeged, Department of PathologySzeged, Hungary.
RP Almasi, Sz (reprint author), University of Szeged, Department of Pathology, Szeged, Hungary.
EM szinti951023@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611365
EP 1611377
DI 10.3389/pore.2023.1611365
PG 13
ER
PT J
AU Tornyi, I
Arkosy, P
Horvath, I
Furka, A
AF Tornyi, Ilona
Arkosy, Peter
Horvath, Ildiko
Furka, Andrea
TI A new perspective on the proper timing of radiotherapy during CDK4/6 inhibitor therapy in patients with “bone-only” metastatic breast cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE breast cancer; radiotherapy; radiosensitivity; CDK4/6 inhibitors; treatment timing
ID breast cancer; radiotherapy; radiosensitivity; CDK4/6 inhibitors; treatment timing
AB The vast majority of hormone positive and HER2 negative advanced breast cancers can be controlled well by endocrine therapy combined with the groundbreaking use of CDK4/6 inhibitors in the metastatic first-line setting. Approximately 50%–60% of these patients have “bone-only” metastatic disease. In oligometastatic cases or if a certain number of uncontrolled lesions develop during the aforementioned therapy, ablative radiotherapy can be delivered or, in symptomatic cases, urgent irradiation is needed with palliative intent. To achieve the most effective results, parallel with good quality of life, the timing of radiotherapy must be determined precisely, taking into account that different cell cycles are involved during different treatment modalities; therefore, optimization of treatment schedules ensures longer and safer post-progression overall survival. The key question is whether the two treatment modalities are safe concurrently or whether they should be administered separately, and if so, what is the optimal sequence and why? This manuscript aims to answer this important question, with a focus on quality of life. Existing publications focus on safety and toxicity profiles, and efficacy is detailed only tangentially and minimally.
C1 [Tornyi, Ilona] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Arkosy, Peter] University of Debrecen, Department of OncologyDebrecen, Hungary.
[Horvath, Ildiko] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Furka, Andrea] University of Debrecen, Department of OncologyDebrecen, Hungary.
RP Horvath, I (reprint author), University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, Debrecen, Hungary.
EM ildiko.horvath@koranyi.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611369
EP 1611376
DI 10.3389/pore.2023.1611369
PG 8
ER
PT J
AU Cegledi, A
Csukly, Z
Fekete, M
Kozma, A
Szemlaky, Zs
Andrikovics, H
Mikala, G
AF Cegledi, Andrea
Csukly, Zoltan
Fekete, Monika
Kozma, Andras
Szemlaky, Zsuzsanna
Andrikovics, Hajnalka
Mikala, Gabor
TI Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; venetoclax; translocation t(6; 14); IGH::CCND3; personalized therapy
ID multiple myeloma; venetoclax; translocation t(6; 14); IGH::CCND3; personalized therapy
AB Introduction: The selective Bcl-2 inhibitor venetoclax has shown promising therapeutic potential in multiple myeloma, particularly in cases associated with t(11;14) IGH::CCND1 translocation. However, the efficacy of venetoclax in myeloma patients with the t(6;14) IGH::CCND3 translocation remains less investigated. Methods: In this study, we conducted a retrospective analysis to investigate the efficacy of venetoclax-based therapy in relapsed/refractory myeloma patients with t(6;14) translocation. The treatment courses of three patients, that included previous therapies and responses to venetoclax, were assessed. Clinical data, laboratory results, and adverse events were analyzed to evaluate treatment outcomes. Results: Our findings demonstrated remarkable therapeutic responses in three consecutive patients with t(6;14) translocation-associated myeloma who received venetoclax-based therapy. Patient 1, a lenalidomide-bortezomibdaratumumab and alkylator treatment refractory patient, achieved sustained stringent complete remission (sCR) after combining carfilzomibdexamethasone with venetoclax, which was his best response ever. Similarly, Patient 2, refractory to frontline bortezomib-thalidomide-dexamethasone therapy, attained CR following a transition to bortezomib-dexamethasonvenetoclax treatment. Patient 3, who was immunomodulatory (IMID)- intolerant, showed a highly favorable response to venetoclaxdexamethasone therapy after his first relapse following autologous stem cell transplantation. No significant adverse effects were observed in any of the patients. Discussion: Our study provides compelling preliminary evidence for the efficacy of venetoclax in t(6;14) translocation-associated myeloma. The outcomes observed in our patients suggest that venetoclax-based therapy holds substantial promise as an effective treatment option for this specific genetic subgroup. Furthermore, the similarities in treatment response between t(11;14) and t(6;14) translocation subgroups highlight the importance of personalized approaches targeting specific genetic abnormalities to optimize therapeutic outcomes.
C1 [Cegledi, Andrea] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Csukly, Zoltan] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Fekete, Monika] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Kozma, Andras] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai LaboratoriumBudapest, Hungary.
[Szemlaky, Zsuzsanna] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Andrikovics, Hajnalka] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Molekularis Genetikai LaboratoriumBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
RP Mikala, G (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Budapest, Hungary.
EM gmikala@dpckorhaz.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611375
EP 1611381
DI 10.3389/pore.2023.1611375
PG 7
ER
PT J
AU Wang, Z
Li, P
Bai, J
Liu, Y
Jiao, G
AF Wang, Zhen
Li, Peng
Bai, Jiayu
Liu, Yujia
Jiao, Guangyu
TI Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE elastography; endobronchial ultrasound-guided transbronchial needle aspiration; mediastinal and hilar lymph nodes; lung cancer; serum tumour markers
ID elastography; endobronchial ultrasound-guided transbronchial needle aspiration; mediastinal and hilar lymph nodes; lung cancer; serum tumour markers
AB Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes. Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated. Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types. Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.
C1 [Wang, Zhen] Shengjing Hospital of China Medical University, Department of Respiratory MedicineShenyang, China.
[Li, Peng] Shengjing Hospital of China Medical University, Department of Respiratory MedicineShenyang, China.
[Bai, Jiayu] The First Affiliated Hospital of China Medical University, Department of RheumatologyShenyang, China.
[Liu, Yujia] Liaoning University of Traditional Chinese Medicine, College of Traditional Chinese MedicineShenyang, China.
[Jiao, Guangyu] Shengjing Hospital of China Medical University, Department of Respiratory MedicineShenyang, China.
RP Jiao, G (reprint author), Shengjing Hospital of China Medical University, Department of Respiratory Medicine, Shenyang, China.
EM jiao_gy@163.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611377
EP 1611389
DI 10.3389/pore.2023.1611377
PG 13
ER
PT J
AU Ferenczi, K
Nagy, FZs
Istenes, I
Eid, H
Bodor, Cs
Timar, B
Demeter, J
AF Ferenczi, Kata
Nagy, Flora Zsofia
Istenes, Ildiko
Eid, Hanna
Bodor, Csaba
Timar, Botond
Demeter, Judit
TI Long term follow-up of refractory/relapsed hairy cell leukaemia patients treated with low-dose vemurafenib between 2013 and 2022 at the Department of Internal Medicine and Oncology, Semmelweis University
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE relapsed/refractory; infection; hairy cell leukemia; BRAF inhibitors; vemurafenib
ID relapsed/refractory; infection; hairy cell leukemia; BRAF inhibitors; vemurafenib
AB Introduction: Hairy cell leukemia (HCL) is an indolent B-cell lymphoproliferative disease. BRAF V600E mutation is detected in nearly all classical HCL cases which offers the possibility of targeted therapy. Objective: The aim of our study was to assess the efficacy of low-dose vemurafenib as well as to assess the long term outcome of HCL patients treated with this drug at the Department of Internal Medicine and Oncology at Semmelweis University. Methods: We report on 10 patients with classical HCL treated with low-dose vemurafenib at our Department between 2013 and 2022. Results: As a result of fixed time low-dose vemurafenib treatment, 5 of 10 patients (5/10) achieved partial remission, 4 (4/10) had stable disease, and 1 (1/10) had MRD positivity. No patients achieved complete remission. The median progression-free survival was 28.5 months while the overall survival was 82 months. Conclusion: We confirm that low dose of vemurafenib is effective and safe in the vast majority of patients with HCL. This small-molecule oral treatment allows to gain valuable time—months or even years—before further, usually parenteral treatment options have to be given or before previous treatment has to be repeated. There are also promising data supporting the combination of vemurafenib with other drugs for the treatment of HCL patients which could provide even further possibility to bridge treatment.
C1 [Ferenczi, Kata] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Nagy, Flora Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Istenes, Ildiko] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Eid, Hanna] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Timar, B (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM timar.botond@semmelweis.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611378
EP 1611385
DI 10.3389/pore.2023.1611378
PG 8
ER
PT J
AU Zhang, F
Wang, X
Zhu, Y
Xia, P
AF Zhang, Fang
Wang, XiaoShuang
Zhu, YuanTing
Xia, Peng
TI Conjoint analysis of clinical, imaging, and pathological features of schistosomiasis and colorectal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE schistosomiasis; colorectal cancer; imaging; t stage; pathology
ID schistosomiasis; colorectal cancer; imaging; t stage; pathology
AB This study aims to examine and compare clinical, radiological, and pathological data between colorectal cancer (CRC) patients with and without schistosomiasis and uncover distinctive CRC characteristics when accompanied by schistosomiasis. This retrospective study is based on data collected from 341 patients diagnosed with CRC post-surgery and pathology. Of these patients, 101 (Group A) were diagnosed with colorectal cancer cooccurring with schistosomiasis (CRC-S), while 240 patients (Group B) were diagnosed with colorectal cancer without concurrent schistosomiasis (CRCNS). Both groups were compared and analyzed based on their clinical data, imaging-based TNM staging, lymph node metastasis, nerve invasion, vascular cancer thrombus, and histopathological differentiation. A Chi-squared test revealed a significant difference in gender distribution between the patients with CRC-S (Group A) and CRC-NS (Group B), with a p -value of 0.043 and χ2 = 4.115. Specifically, a higher incidence rate was observed among males in Group A. There was a difference in the overall distribution of TNM staging between the two groups (p = 0.034, χ2 = 6.764). After pairwise comparison, a statistically significant difference was observed in the T3 stage (p <0.05). The proportion of the T3 stage in Group A was significantly higher than that in Group B, indicating certain advantages. There was a difference in postoperative histopathological grading between the two groups (p = 0.005, χ2 = 10.626). After pairwise comparison, a statistically significant difference was observed between the well-differentiated adenocarcinoma and the moderately and poorly differentiated adenocarcinoma (p <0.05), with a higher proportion of welldifferentiated patients in Group A compared to Group B. There was no significant difference in age, lymph node metastasis, nerve invasion, and vascular invasion between the two groups of patients (p > 0.05). Among the 101 patients with CRC-S, 87 (86%) showed linear calcification on CT imaging. Patients with CRC-S are mainly male, with tumor staging mostly in the middle stage, high tumor differentiation, and low malignancy. CT imaging can help identify the presence of lumps and linear calcification indicative of schistosome deposits. MRI can early clarify TNM staging and determine the presence of lymph node metastasis and nerve and vascular invasion.
C1 [Zhang, Fang] Jingzhou Hospital Affiliated to Yangtze University, Department of RadiologyJingzhou, China.
[Wang, XiaoShuang] Jingzhou Hospital Affiliated to Yangtze University, Department of RadiologyJingzhou, China.
[Zhu, YuanTing] Jingzhou Hospital Affiliated to Yangtze University, Department of PathologyJingzhou, China.
[Xia, Peng] Yangtze University, School of Basic Medicine, Health Science Center, Department of ParasitologyJingzhou, China.
RP Xia, P (reprint author), Yangtze University, School of Basic Medicine, Health Science Center, Department of Parasitology, Jingzhou, China.
EM 805451046@qq.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611396
EP 1611403
DI 10.3389/pore.2023.1611396
PG 8
ER
PT J
AU Verma, P
Rishi, B
George, GN
Kushwaha, N
Dhandha, H
Kaur, M
Jain, A
Jain, A
Chaudhry, S
Singh, A
Siraj, F
Misra, A
AF Verma, Priyanka
Rishi, Bhavika
George, Grace Noreen
Kushwaha, Neetu
Dhandha, Himanshu
Kaur, Manpreet
Jain, Ankur
Jain, Aditi
Chaudhry, Sumita
Singh, Amitabh
Siraj, Fouzia
Misra, Aroonima
TI Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE reactive oxygen species (ROS); recent advances; future directions; cancer therapy; ferroptosis
ID reactive oxygen species (ROS); recent advances; future directions; cancer therapy; ferroptosis
AB A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.
C1 [Verma, Priyanka] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Rishi, Bhavika] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[George, Grace Noreen] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Kushwaha, Neetu] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Dhandha, Himanshu] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Kaur, Manpreet] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Jain, Ankur] Vardhman Mahavir Medical College and Safdarjung HospitalNew Delhi, India.
[Jain, Aditi] Vardhman Mahavir Medical College and Safdarjung HospitalNew Delhi, India.
[Chaudhry, Sumita] Vardhman Mahavir Medical College and Safdarjung HospitalNew Delhi, India.
[Singh, Amitabh] Vardhman Mahavir Medical College and Safdarjung HospitalNew Delhi, India.
[Siraj, Fouzia] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
[Misra, Aroonima] Indian Council of Medical Research-National Institute of Pathology, Department of Health ResearchNew Delhi, India.
RP Misra, A (reprint author), Indian Council of Medical Research-National Institute of Pathology, Department of Health Research, New Delhi, India.
EM dr.aroo.2402@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611415
EP 1611426
DI 10.3389/pore.2023.1611415
PG 12
ER
PT J
AU Kisivan, K
Farkas, A
Kovacs, P
Glavak, Cs
Lukacs, G
Mahr, K
Szabo, Zs
Csima, PM
Gulyban,
Toth, Z
Kaposztas, Zs
Lakosi, F
AF Kisivan, Katalin
Farkas, Andrea
Kovacs, Peter
Glavak, Csaba
Lukacs, Gabor
Mahr, Karoly
Szabo, Zsolt
Csima, Petone Melinda
Gulyban, Akos
Toth, Zoltan
Kaposztas, Zsolt
Lakosi, Ferenc
TI Pancreatic SABR using peritumoral fiducials, triggered imaging and breath-hold
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE motion control; pancreatic cancer; triggered imaging; stereotactic ablative radiotherapy; deep inspiration breath hold
ID motion control; pancreatic cancer; triggered imaging; stereotactic ablative radiotherapy; deep inspiration breath hold
AB Background: We aim to present our linear accelerator-based workflow for pancreatic stereotactic ablative radiotherapy (SABR) in order to address the following issues: intrafractional organ motion management, Cone Beam CT (CBCT) image quality, residual errors with dosimetric consequences, treatment time, and clinical results. Methods: Between 2016 and 2021, 14 patients with locally advanced pancreatic cancer were treated with induction chemotherapy and SABR using volumetric modulated arc therapy (VMAT). Internal target volume (ITV) concept (5), phasegated (4), or breath hold (5) techniques were used. Treatment was verified by CBCT before and after irradiation, while tumor motion was monitored and controlled by kV triggered imaging and beam hold using peritumoral surgical clips. Beam interruptions and treatment time were recorded. The CBCT image quality was scored and supplemented by an agreement analysis (Krippendorff’s- α) of breath-hold CBCT images to determine the position of OARs relative to the planning risk volumes (PRV). Residual errors and their dosimetry impact were also calculated. Progression free (PFS) and overall survival (OS) were assessed by the Kaplan-Meier analysis with acute and late toxicity reporting (CTCAEv4). Results: On average, beams were interrupted once (range: 0–3) per treatment session on triggered imaging. The total median treatment time was 16.7 ± 10.8 min, significantly less for breath-hold vs. phase-gated sessions (18.8 ± 6.2 vs. 26.5 ± 13.4, p < 0.001). The best image quality was achieved by breath hold CBCT. The Krippendorff’s-α test showed a strong agreement among five radiation therapists (mean K-α value: 0.8 (97.5%). The mean residual errors were <0.2 cm in each direction resulting in an average difference of <2% in dosimetry for OAR and target volume. Two patients received offline adaptation. The median OS/PFS after induction chemotherapy and SABR was 20/12 months and 15/8 months. No Gr. ≥2 acute/late RT-related toxicity was noted. Conclusion: Linear accelerator based pancreatic SABR with the combination of CBCT and triggered imaging + beam hold is feasible. Peritumoral fiducials improve utility while breath-hold CBCT provides the best image quality at a reasonable treatment time with offline adaptation possibilities. In well-selected cases, it can be an effective alternative in clinics where CBCT/MRI-guided online adaptive workflow is not available.
C1 [Kisivan, Katalin] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Farkas, Andrea] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Kovacs, Peter] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Glavak, Csaba] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
[Lukacs, Gabor] Somogy Megyei Kaposi Mor Oktato Korhaz, Klinikai OnkologiaKaposvar, Hungary.
[Mahr, Karoly] Zala Megyei Szent Rafael Korhaz, OnkologiaZalaegerszeg, Hungary.
[Szabo, Zsolt] Zala Megyei Szent Rafael Korhaz, OnkologiaZalaegerszeg, Hungary.
[Csima, Petone Melinda] Hungarian University of Agricultural and Life Sciences, Institute of EducationGodollo, Hungary.
[Gulyban, Akos] Institut Jules Bordet, Department of Medical PhysicsBrussels, Belgium.
[Toth, Zoltan] MEDICOPUS Egeszsegugyi Szolgaltato Kozhasznu Nonprofit Kft.Kaposvar, Hungary.
[Kaposztas, Zsolt] Somogy Megyei Kaposi Mor Oktato Korhaz, Sebeszeti OsztalyKaposvar, Hungary.
[Lakosi, Ferenc] Kaposvar University, Department of Radiation OncologyKaposvar, Hungary.
RP Lakosi, F (reprint author), Kaposvar University, Department of Radiation Oncology, Kaposvar, Hungary.
EM lakosiferenc@yahoo.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611456
EP 1611467
DI 10.3389/pore.2023.1611456
PG 12
ER
PT J
AU Hasanova, A
Asadov, Ch
Karimova, N
Shirinova, A
Aliyeva, G
Alimirzoyeva, Z
AF Hasanova, Aypara
Asadov, Chingiz
Karimova, Nigar
Shirinova, Aytan
Aliyeva, Gunay
Alimirzoyeva, Zohra
TI Spectrum of BCR-ABL mutations in Azerbaijanian imatinib-resistant patients with chronic myeloid leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic myeloid leukemia; mutation; tyrosine kinase inhibitor resistance; kinase domain; BCR-ABL
ID chronic myeloid leukemia; mutation; tyrosine kinase inhibitor resistance; kinase domain; BCR-ABL
AB Objective: BCR-ABL1 kinase domain (KD) mutations can lead to resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Here, we present the first report of the spectrum of mutations in the BCR-ABL1 KD of CML patients from Azerbaijan. Materials and methods: Samples for mutation screening were obtained from patients experiencing resistance to first line TKIs or from patients in acceleration phase (AP) or blast crisis (BC) at the time of diagnosis. The cDNA region corresponding to BCR-ABL1 KD was sequenced by pyrosequencing method. The χ2 test was used to assess the association of categorical variables between mutation-positive and -negative groups. In addition, the Kaplan-Meier method was applied to generate survival curves. Results: Eight different pointmutations were identified in 22 (13.4%) out of 163CML patients experiencing resistance to TKIs. The types of mutations detected were as follows: Contact binding site mutations 50% (11), SH2 domain mutations 27.4% (six), P-loop mutations 18.1% (four), and SH3 domain mutations accounting for 4.5% (one). The most common mutation was T315I, accounting for 5% (n = 8) of all patients. Significant association was identified between BCR-ABL1 mutations and additional chromosomal aberrations as well as between the mutations and disease phases (p < 0.05). Twelve out of 22 patients with BCR-ABL1 mutations and seven out of eight with T315I were in BC. Overall survival (OS) of the patients with BCRABL1 mutations was significantly lower comparing to the patients with nomutation (p < 0.05) and 8 patients with T315I mutation presented OS of 0%. Conclusion: T315I was the most commonly identified BCR-ABL1 mutation in TKI-resistant CML patients of Azerbaijani origin, being associated with disease progression and poor OS.
C1 [Hasanova, Aypara] Institute of Hematology and Transfusiology, Leukemogenesis LaboratoryBaku, Azerbaijan.
[Asadov, Chingiz] Institute of Hematology and Transfusiology, Hematopoiesis DepartmentBaku, Azerbaijan.
[Karimova, Nigar] Institute of Genetic Resources, Biotechnology Department, Human Genetics LaboratoryBaku, Azerbaijan.
[Shirinova, Aytan] Institute of Hematology and Transfusiology, Hematology DepartmentBaku, Azerbaijan.
[Aliyeva, Gunay] Institute of Hematology and Transfusiology, Hematopoiesis DepartmentBaku, Azerbaijan.
[Alimirzoyeva, Zohra] Institute of Hematology and Transfusiology, Hematology DepartmentBaku, Azerbaijan.
RP Aliyeva, G (reprint author), Institute of Hematology and Transfusiology, Hematopoiesis Department, Baku, Azerbaijan.
EM galiyeva@rocketmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611518
EP 1611528
DI 10.3389/pore.2023.1611518
PG 11
ER
PT J
AU Makk, E
Bohonyi, N
Oszter, A
Eles, K
Tornoczky, T
Toth, A
Kalman, E
Kovacs, K
AF Makk, Evelin
Bohonyi, Noemi
Oszter, Angela
Eles, Klara
Tornoczky, Tamas
Toth, Arnold
Kalman, Endre
Kovacs, Krisztina
TI Comparative analysis of EZH2, p16 and p53 expression in uterine carcinosarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE uterine cancer; carcinosarcoma; EZH2; p16; p53
ID uterine cancer; carcinosarcoma; EZH2; p16; p53
AB Introduction: The role of p16 and p53 immunohistochemistry in the diagnosis of rare and aggressive uterine carcinosarcoma (UCS) has been well established. However, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a member of the polycomb group family is a relatively new biomarker, with limited published data on its significance in this tumor type. The goal of this study was to examine EZH2 expression in UCS and its components, in correlation with morphological features, and p16 and p53 staining patterns. Methods: Twenty-eight UCSs were included in the study. EZH2, p16 and p53 immunoreactivity were assessed independently by two pathologists in both tumor components (epithelial and mesenchymal). EZH2 and p16 immunostains were scored semiquantitatively: based on the percentage and intensity of tumor cell staining a binary staining index (“high- or lowexpressing”) was calculated. The p53 staining pattern was evaluated as wildtype or aberrant (diffuse nuclear, null, or cytoplasmic expression). Statistical tests were used to evaluate the correlation between staining patterns for all three markers and the different tumor components and histotypes. Results: High EZH2 and p16 expression and aberrant p53 patterns were present in 89.3% 78.6% and 85.7% of the epithelial component and in 78.6%, 62.5% and 82.1% of the mesenchymal component, respectively. Differences among these expression rates were not found to be significant (p > 0.05). Regarding the epithelial component, aberrant p53 pattern was found to be significantly (p = 0.0474) more frequent in the serous (100%) than in endometrioid (66.6%) histotypes. Within the mesenchymal component, p53 null expression pattern occurred significantly (p = 0.0257) more frequently in heterologous sarcoma components (71.4%) compared to the homologous histotype (18.8%). Conclusion: In conclusion, EZH2, p16 and p53 seem to play a universal role in the pathogenesis of UCS; however, a distinctive pattern of p53 expression appears to exist between the serous and endometrioid carcinoma components and also between the homologous and heterologous sarcoma components.
C1 [Makk, Evelin] University of Pecs, Department of PathologyPecs, Hungary.
[Bohonyi, Noemi] Pecsi Tudomanyegyetem, Altalanos Orvostudomanyi Kar, Szuleszeti es Nogyogyaszati KlinikaPecs, Hungary.
[Oszter, Angela] University of Pecs, Department of PathologyPecs, Hungary.
[Eles, Klara] University of Pecs, Department of PathologyPecs, Hungary.
[Tornoczky, Tamas] University of Pecs, Department of PathologyPecs, Hungary.
[Toth, Arnold] PTE KK, Radiologiai KlinikaPecs, Hungary.
[Kalman, Endre] University of Pecs, Department of PathologyPecs, Hungary.
[Kovacs, Krisztina] University of Pecs, Department of PathologyPecs, Hungary.
RP Makk, E (reprint author), University of Pecs, Department of Pathology, Pecs, Hungary.
EM makk.evelin@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611547
EP 1611557
DI 10.3389/pore.2023.1611547
PG 11
ER
PT J
AU Zhang, L
Yuan, P
Cao, Q
Mu, J
Ying, J
Guo, Ch
AF Zhang, Letian
Yuan, Pei
Cao, Qi
Mu, Jiali
Ying, Jianming
Guo, Changyuan
TI Expression of Concern: Case report: A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
AB Following publication, the authors contacted the Editorial Office stating that the findings reported in the article are no longer supported by the analyses. With this notice, Pathology and Oncology Research states its awareness of concerns regarding “A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma” published on 12 June 2023. This expression of concern has been posted while Pathology and Oncology Research awaits further clarification from the authors. It will be updated accordingly after that time.
C1 [Zhang, Letian] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Yuan, Pei] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Cao, Qi] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Mu, Jiali] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Ying, Jianming] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
[Guo, Changyuan] Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of PathologyBeijing, China.
RP Guo, Ch (reprint author), Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Department of Pathology, Beijing, China.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611563
EP 1611563
DI 10.3389/pore.2023.1611563
PG 1
ER
PT J
AU Pathology and Oncology Research, EO
AF Pathology and Oncology Research, Editorial Office
TI Retraction: Frequencies of Porphyromonas gingivalis detection in oral-digestive tract tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB The journal retracts the 1 April 2021 article cited above. Following publication, concerns were raised regarding data misrepresentation. Following provision of raw data by the authors, the Editor in Chief concluded that the article’s conclusions and assertions were not sufficiently supported by the findings from the material provided; therefore, the article has been retracted. The authors do not agree to this retraction.
C1 [Pathology and Oncology Research, Editorial Office] Frontiers Media SALausanne, Switzerland.
RP Pathology and Oncology Research, EO (reprint author), Frontiers Media SA, Lausanne, Switzerland.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611616
EP 1611616
DI 10.3389/pore.2023.1611616
PG 1
ER
PT J
AU Editorial Office, PaOR
AF Editorial Office, Pathology and Oncology Research
TI Retraction: Associations of porphyromonas gingivalis infection and low beclin1 expression with clinicopathological parameters and survival of esophageal squamous cell carcinoma patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB The journal retracts the 08 December 2021 article cited above. Following publication, concerns were raised regarding data misrepresentation. In particular, multiple discrepancies were identified in the flow cytometry graphs, western blots and bar graphs in Figure 4. Following provision of raw data by the authors, the Editor in Chief concluded that the article’s conclusions and assertions were not sufficiently supported by the findings from the material provided; therefore, the article has been retracted. The authors do not agree to this retraction.
C1 [Editorial Office, Pathology and Oncology Research] Frontiers Media SALausanne, Switzerland.
RP Editorial Office, PaOR (reprint author), Frontiers Media SA, Lausanne, Switzerland.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD NOV
PY 2023
VL 29
IS 4
BP 1611617
EP 1611617
DI 10.3389/pore.2023.1611617
PG 1
ER
PT J
AU Hu, L
Tiesinga, J
AF Hu, Lina
Tiesinga, James
TI Case report: Primary vulvar adenocarcinoma of mammary gland type—its genetic characteristics by focused next-generation sequencing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE MLVA; mutations by NGS; immune markers; triple positive; immunohistochemical features
ID MLVA; mutations by NGS; immune markers; triple positive; immunohistochemical features
AB Mammary-like vulvar adenocarcinoma (MLVA) is an exceedingly rare subtype of vulvar adenocarcinoma that shares features with mammary gland tissue. Due to its rarity and lack of consensus, MLVA presents diagnostic challenges to pathologists. We present the case of a 59-yearold female with an ulceratedmass on the right side of the external genitalia, diagnosed as MLVA. Comprehensive immunohistochemistry (IHC) and gene sequencing studies were performed to characterize the tumor. IHC analysis revealed triple expression of hormonal receptors (estrogen receptor, progesterone receptor, and HER2), supporting the mammary gland origin of the tumor. Gene sequencing identified unique genetic mutations associated with the expression of hormonal markers. One fusion gene (ERBB2-NAGLU) has not been reported in any tumors, and other mutations with unique mutation types have not been previously reported in MLVA. Our findings shed light on the molecular characteristics of MLV and may help improve the diagnosis and treatment of this rare type of vulvar adenocarcinoma.
C1 [Hu, Lina] Alaska Native Medical Center, Department of PathologyAnchorage, AK, USA.
[Tiesinga, James] Alaska Native Medical Center, Department of PathologyAnchorage, AK, USA.
RP Hu, L (reprint author), Alaska Native Medical Center, Department of Pathology, Anchorage, USA.
EM lxhu@anthc.org
CR Grewal JK, Eirew P, Jones M, Chiu K, Tessier-Cloutier B, Karnezis AN, et al. Detection and genomic characterization of a mammary-like adenocarcinoma. Cold Spring Harb Mol Case Stud, 2017, 3(6):a002170., DOI 10.1101/mcs.a002170
Stueben BL, Lara JF. Primary adnexal adenocarcinoma of the vulva: a diagnosis of exclusion based on location, immunohistochemistry, and pattern of spread. Gynecol Oncol Case Rep, 2013, 4:7–8., DOI 10.1016/j.gynor.2012.11.002
Niakan S, Love H, Cao Q, Kawar N. Primary invasive lobular carcinoma arising in mammary-like glands of the vulva managed with neoadjuvant trastuzumabbased chemotherapy, excision, and sentinel lymph node biopsy. Clin case Rep, 2021, 9(1):118–22., DOI 10.1002/ccr3.3475
Kalwiba C, Lunn J, Wu etc H. Adenocarcinoma of mammary-like glands of the vulva: a case report and literature review. South Afr J Gynaecol Oncol, 2022, 14(1).
Moraisl M, Vaz Silva J, Tavares MV. Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases. BMJ case Rep, 2022, 15(6):e245580., DOI 10.1136/bcr-2021-245580
Tessier-Cloutier B, Asleh-Aburaya K, Shah V, McCluggage WG, Tinker A, Gilks CB. Molecular subtyping of mammary-like adenocarcinoma of the vulva shows molecular similarity to breast carcinomas. Histopathology, 2017, 71(3): 446–52., DOI 10.1111/his.13239
Veeraraghavan J, Tan Y, Cao X-X, Kim JA, Wang X, Chamness GC, et al. Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers. Nat Commun, 2014, 5:4577., DOI 10.1038/ ncomms5577
Li L, Lin L, Veeraraghavan J, Hu Y, Wang X, Lee S, et al. Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance. Breast Cancer Res, 2020, 22(84):84–15., DOI 10.1186/s13058-020-01325-3
Vitale SR, Ruigrok-Ritstier K, Timmermans AM, Foekens R, Trapman-Jansen AMAC, Beaufort CM, et al. The prognostic and predictive value of ESR1 fusion gene transcripts in primary breast cancer. BMC Cancer, 2022, 165:165–16., DOI 10.1186/ s12885-022-09265-1
Zardavas D, Phillips WA, Loi S. PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data. Breast Cancer Res, 2014, 16(1):201., DOI 10.1186/bcr3605
Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490:61–70., DOI 10.1038/nature11412
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611376
EP 1611381
DI 10.3389/pore.2024.1611376
PG 6
ER
PT J
AU Vargova, D
Kolkova, Z
Dargaj, J
Bris, L
Luptak, J
Dankova, Z
Franova, S
Svihra, J
Slavik, P
Sutovska, M
AF Vargova, Daniela
Kolkova, Zuzana
Dargaj, Jan
Bris, Lukas
Luptak, Jan
Dankova, Zuzana
Franova, Sona
Svihra, Jan
Slavik, Pavol
Sutovska, Martina
TI Analysis of HIF-1α expression and genetic polymorphisms in human clear cell renal cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HIF-1α; SNP; RCC; tumor; kidney
ID HIF-1α; SNP; RCC; tumor; kidney
AB Introduction: Clear cell renal cell carcinoma (ccRCC) is mostly diagnosed incidentally and has relatively high recurrence rates. Alterations in VHL/HIF and mTOR pathways are commonly present in ccRCC. The present study attempted to identify potential diagnostic markers at the biochemical and molecular level. Methods: In total, 54 subjects (36 patients with ccRCC and 18 cancer-free controls) were enrolled. ELISA was used to measure the levels of HIF-1α in the tumor and healthy kidney tissue. The association between five selected SNPs (rs779805, rs11549465, rs2057482, rs2295080 and rs701848) located in genes of pathologically relevant pathways (VHL/HIF and mTOR) and the risk of ccRCC in the Slovak cohort was studied using real-time PCR. Results: Significant differences in HIF-1α tissue levels were observed between the tumor and healthy kidney tissue (p < 0.001). In the majority (69%) of cases, the levels of HIF-1α were higher in the kidney than in the tumor. Furthermore, the concentration of HIF-1α in the tumor showed a significant positive correlation with CCL3 and IL-1β (p (R2) 0.007 (0.47); p (R2) 0.011 (0.38). No relationship between intratumoral levels of HIF-1α and clinical tumor characteristics was observed. Rs11549465, rs2057482 in the HIF1A gene did not correlate with the expression of HIF-1α either in the tumor or in the normal kidney. None of the selected SNPs has influenced the susceptibility to ccRCC. Conclusion: More research is neccesary to elucidate the role of HIF-1α in the pathogenesis of ccRCC and the association between selected SNPs and susceptibility to this cancer.
C1 [Vargova, Daniela] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of PharmacologyMartin, Slovakia.
[Kolkova, Zuzana] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center MartinMartin, Slovakia.
[Dargaj, Jan] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of UrologyMartin, Slovakia.
[Bris, Lukas] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of UrologyMartin, Slovakia.
[Luptak, Jan] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of UrologyMartin, Slovakia.
[Dankova, Zuzana] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center MartinMartin, Slovakia.
[Franova, Sona] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of PharmacologyMartin, Slovakia.
[Svihra, Jan] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of UrologyMartin, Slovakia.
[Slavik, Pavol] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathological AnatomyMartin, Slovakia.
[Sutovska, Martina] Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of PharmacologyMartin, Slovakia.
RP Vargova, D (reprint author), Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Martin, Slovakia.
EM vargova238@uniba.sk
CR Warren AY, Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J Urol, 2018, 36: 1913–26., DOI 10.1007/s00345-018-2447-8
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611444
EP 1611453
DI 10.3389/pore.2023.1611444
PG 10
ER
PT J
AU Bely, M
Apathy,
AF Bely, Miklos
Apathy, Agnes
TI Crystal induced arthropathies—a comparative study of 40 patients with apatite rheumatism, chondrocalcinosis and primary synovial chondromatosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE apatite rheumatism; chondrocalcinosis; primary synovial chondromatosis; conventional stains; non-staining technique
ID apatite rheumatism; chondrocalcinosis; primary synovial chondromatosis; conventional stains; non-staining technique
AB Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bely and Apathy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffinembedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bely and Apathy (2013). Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed. Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bely and Apathy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.
C1 [Bely, Miklos] St John's Hospital, Department of PathologyBudapest, Hungary.
[Apathy, Agnes] St. Margaret Clinic, Department of RheumatologyBudapest, Hungary.
RP Bely, M (reprint author), St John's Hospital, Department of Pathology, Budapest, Hungary.
EM dr.bely.miklos@gmail.com
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Uhthoff HK, Loehr JW. Calcific tendinopathy of the rotator cuff: pathogenesis, diagnosis, and management. J Am Acad Orthopaedic Surgeons, 1997, 5(4):183–91., DOI 10.5435/00124635-199707000-00001
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611454
EP 1611468
DI 10.3389/pore.2024.1611454
PG 15
ER
PT J
AU Ferreira de Araujo, GM
Almondes Santana Lemos, EL
Negromonte Guerra, LP
dos Santos Lima Didjurgeit, MF
Cezar, BA
Faquini, VI
Cirne de Azevedo Filho, RH
AF Ferreira de Araujo, Gomes Mayle
Almondes Santana Lemos, Euripedes Luiz
Negromonte Guerra, Lucas Pedro
dos Santos Lima Didjurgeit, Marcia Fernanda
Cezar, Batista Auricelio
Faquini, Vilela Igor
Cirne de Azevedo Filho, Rocha Hildo
TI Supratentorial meningeal melanocytoma mimicking meningioma: case report and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE primary melanocytic tumor; melanocytoma; brain tumor; primary brain tumor; primary meningeal melanocytomas
ID primary melanocytic tumor; melanocytoma; brain tumor; primary brain tumor; primary meningeal melanocytomas
AB Introduction: Primary melanocytic tumors originating from CNS melanocytes are rare, with a low incidence of 0.7 cases per 10 million annually. This study focuses on primary leptomeningeal melanocytomas, emphasizing their epidemiology, clinical characteristics, and diagnostic challenges. Despite their infrequency, these tumors warrant attention due to their unique features and potential for local recurrence. Case Report: A 32-year-old female presented with syncope and seizures, leading to the discovery of two left-sided supratentorial lesions initially misidentified as convexity meningiomas. Detailed imaging suggested meningioma-like features, but intraoperative findings revealed unexpected hyperpigmented lesions. Histopathological examination, supported by immunohistochemistry, confirmed primary leptomeningeal melanocytoma. The surgical approach and subsequent management are discussed. Discussion: The discussion emphasizes challenges in diagnosing primary leptomeningeal melanocytomas. Treatment debates, especially regarding adjuvant radiotherapy, are explored. Recurrence risks stress the importance of vigilant follow-up, advocating for complete surgical resection as the primary approach. The rarity of supratentorial cases adds complexity to diagnosis, necessitating a multidisciplinary approach. Insights from this case contribute to understanding and managing primary leptomeningeal melanocytomas, addressing challenges in differentiation from more common tumors and prompting ongoing research for refined diagnostics and optimized treatments. Conclusion: This study contributes insights into primary leptomeningeal melanocytomas, highlighting their rarity in supratentorial regions. The case underscores the importance of a multidisciplinary approach, incorporating clinical, radiological, and histopathological expertise for accurate diagnosis and tailored management. Ongoing research is crucial to refine treatment strategies, enhance prognostic precision, and improve outcomes for individuals with this uncommon CNS neoplasm.
C1 [Ferreira de Araujo, Gomes Mayle] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
[Almondes Santana Lemos, Euripedes Luiz] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
[Negromonte Guerra, Lucas Pedro] Universidade Federal de Pernambuco, Center for Medical SciencesRecife, Brazil.
[dos Santos Lima Didjurgeit, Marcia Fernanda] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
[Cezar, Batista Auricelio] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
[Faquini, Vilela Igor] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
[Cirne de Azevedo Filho, Rocha Hildo] Hospital da Restauracao, Department of NeurosurgeryRecife, Brazil.
RP Negromonte Guerra, LP (reprint author), Universidade Federal de Pernambuco, Center for Medical Sciences, Recife, Brazil.
EM pedronegromontee@gmail.com
CR Brat DJ, Giannini C, Scheithauer BW, Burger PC. Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol, 1999, 23(7): 745–54., DOI 10.1097/00000478-199907000-00001
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611482
EP 1611488
DI 10.3389/pore.2023.1611482
PG 7
ER
PT J
AU Batar, P
Alizadeh, H
Rokszin, Gy
Abonyi-Toth, Zs
Demeter, J
AF Batar, Peter
Alizadeh, Hussain
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Demeter, Judit
TI Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic myeloid leukemia; real-word evidence; tyrosine kinase inhibitors; treatment outcome; overall survival
ID chronic myeloid leukemia; real-word evidence; tyrosine kinase inhibitors; treatment outcome; overall survival
AB Purpose: This study aimed to provide real-world evidence on the characteristics, treatment patterns, and outcomes of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) treatment in Hungary between 2011 and 2019. Patients and methods: This nationwide, retrospective study included patients who were newly diagnosed with CML in Hungarian clinical practice between January 2011 and December 2019. The analysis was based on the reimbursed prescription claims for imatinib, bosutinib, dasatinib, nilotinib, or ponatinib with the ICD-10 code C9210 in a public pharmacy between January 2009 and December 2019 using data from the National Health Insurance Fund (NHIF) of Hungary. CML incidence and prevalence, TKI treatment patterns, comorbidities, and overall survival (OS) were examined. Results: Between 2011 and 2019, altogether 1,407 patients were diagnosed with CML, with an annual average of 156 patients. The number of patients newly initiating first-line TKI therapy for CML significantly increased between 2011 and 2019 (2011: n = 136 vs. 2019: n = 191; p = 0.0043). Nilotinib was typically prescribed for younger patients (≤64 years), while older patients (≥65 years) mostly received imatinib. The most common comorbidity of CML patients was hypertension, and the proportion of patients with other malignancies was relatively high in all treatment groups. 5-year OS was 77.1% during the whole study period. Patients initiating first-line TKI treatment for CML in 2015 had significantly better 4-year OS compared to those starting treatment in 2011 (82.4% vs. 73.5%, respectively, (HR 0.53 (95%CI 0.32–0.87) p = 0.0118). Conclusion: This study is the first to provide insights into the characteristics, treatment patterns, and outcomes of CML patients treated with TKIs in Hungarian clinical practice between 2011 and 2019. We found slightly lower OS rates compared to other European countries, however, there was a statistically significant improvement in 4-year OS during the study period. The management of CML was in line with international guidelines and recommendations.
C1 [Batar, Peter] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Alizadeh, Hussain] University of Pecs, Medical School, Clinical Center, 1st Department of Medicine, Division of HaematologyPecs, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Batar, P (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM pbatar@med.unideb.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611497
EP 1611507
DI 10.3389/pore.2024.1611497
PG 11
ER
PT J
AU Dai, J
Jiang, Y
Hu, H
Zhang, Sh
Chen, Y
AF Dai, Jie
Jiang, Yong
Hu, Haoyue
Zhang, Shuang
Chen, Yue
TI Extracellular vesicles as modulators of glioblastoma progression and tumor microenvironment
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE extracellular vesicles; tumor microenvironment; glioblastoma; exosomes; microvesicles
ID extracellular vesicles; tumor microenvironment; glioblastoma; exosomes; microvesicles
AB Glioblastoma is the most aggressive brain tumor with extremely poor prognosis in adults. Routine treatments include surgery, chemotherapy, and radiotherapy; however, these may lead to rapid relapse and development of therapy-resistant tumor. Glioblastoma cells are known to communicate with macrophages, microglia, endothelial cells, astrocytes, and immune cells in the tumor microenvironment (TME) to promote tumor preservation. It was recently demonstrated that Glioblastoma-derived extracellular vesicles (EVs) participate in bidirectional intercellular communication in the TME. Apart from promoting glioblastoma cell proliferation, migration, and angiogenesis, EVs and their cargos (primarily proteins and miRNAs) can act as biomarkers for tumor diagnosis and prognosis. Furthermore, they can be used as therapeutic tools. In this review, the mechanisms of Glioblastoma-EVs biogenesis and intercellular communication with TME have been summarized. Moreover, there is discussion surrounding EVs as novel diagnostic structures and therapeutic tools for glioblastoma. Finally, unclear questions that require future investigation have been reviewed.
C1 [Dai, Jie] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Department of PathologyChengdu, China.
[Jiang, Yong] Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Department of NeurosurgeryChengdu, China.
[Hu, Haoyue] University of Electronic Science and Technology of China, School of Medicine, Sichuan Cancer Center, Sichuan Cancer Hospital and Institute, Medical OncologyChengdu, China.
[Zhang, Shuang] Capital Medical University, Beijing Shijitan Hospital, Department of PathologyBeijing, China.
[Chen, Yue] Capital Medical University, Beijing Shijitan Hospital, Department of PathologyBeijing, China.
RP Chen, Y (reprint author), Capital Medical University, Beijing Shijitan Hospital, Department of Pathology, Beijing, China.
EM chenyue8249@163.com
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Tandsaether, Randi Maren
Lobmaier, Ingvild
Lund-Iversen, Marius
Lien-Dahl, Thomas
Micci, Francesca
Panagopoulos, Ioannis
TI Genetic characterization of intramuscular myxomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE intramuscular myxoma; chromosomal aberrations; GNAS; codon 201; codon 227; Sanger sequencing; Ion torrent
ID intramuscular myxoma; chromosomal aberrations; GNAS; codon 201; codon 227; Sanger sequencing; Ion torrent
AB Introduction: Intramuscular myxomas are benign tumors that are challenging to diagnose, especially on core needle biopsies. Acquired chromosomal aberrations and pathogenic variants in codon 201 or codon 227 in GNAS complex locus gene (GNAS) have been reported in these tumors. Here we present our genetic findings in a series of 22 intramuscular myxomas. Materials and methods: The tumors were investigated for the presence of acquired chromosomal aberrations using G-banding and karyotyping. Pathogenic variants in codon 201 or codon 227 of GNAS were assessed using direct cycle Sanger sequencing and Ion AmpliSeq Cancer Hotspot Panel v2 methodologies. Results: Eleven tumors carried chromosomal abnormalities. Six tumors had numerical, four had structural, and one had both numerical and structural chromosomal aberrations. Gains of chromosomes 7 and 8 were the most common abnormalities being found in five and four tumors respectively. Pathogenic variants in GNAS were detected in 19 myxomas (86%) with both methodologies. The detected pathogenic variants were p.R201H in nine cases (seven with abnormal and two with normal karyotypes), p.R201C in five cases, all with normal karyotypes, p.R201S in three cases (two with abnormal and one with normal karyotype), p.R201G in one case with a normal karyotype, and p.Q227E in one case with a normal karyotype. Conclusion: Firstly, our data indicate a possible association between chromosomal abnormalities and GNAS pathogenic variants in intramuscular myxomas. Secondly, the presence of the rare pathogenic variants R201S, p.R201G and p.Q227E in 26% (5 out of 19) of myxomas with GNAS pathogenic variants shows that methodologies designed to detect only the common “hotspot” of p.R201C and p.R201H will give false negative results. Finally, a comparison between Ion AmpliSeq Cancer Hotspot Panel v2 and direct cycle Sanger sequencing showed that direct cycle Sanger sequencing provides a quick, reliable, and relatively cheap method to detect GNAS pathogenic variants, matching even the most cutting-edge sequencing methods.
C1 [Hatchett, John William] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
[Brunetti, Marta] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
[Andersen, Kristin] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
[Tandsaether, Randi Maren] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
[Lobmaier, Ingvild] The Norwegian Radium Hospital, University of Oslo, Department of PathologyOslo, Norway.
[Lund-Iversen, Marius] The Norwegian Radium Hospital, University of Oslo, Department of PathologyOslo, Norway.
[Lien-Dahl, Thomas] The Norwegian Radium Hospital, University of Oslo, Department of PathologyOslo, Norway.
[Micci, Francesca] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
[Panagopoulos, Ioannis] The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer CytogeneticsOslo, Norway.
RP Panagopoulos, I (reprint author), The Norwegian Radium Hospital, Oslo University Hospital, Institute for Cancer Genetics and Informatics, Section for Cancer Cytogenetics, Oslo, Norway.
EM ioannis.panagopoulos@rrresearch.no
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611553
EP 1611562
DI 10.3389/pore.2024.1611553
PG 10
ER
PT J
AU Sakurai, Sh
Ishida, Y
Shintani, T
Yamasaki, S
Matsui, K
Hamana, T
Nobumoto, T
Yanamoto, S
Hayashido, Y
AF Sakurai, Shigeru
Ishida, Yasutaka
Shintani, Tomoaki
Yamasaki, Sachiko
Matsui, Kensaku
Hamana, Tomoaki
Nobumoto, Tadayoshi
Yanamoto, Souichi
Hayashido, Yasutaka
TI Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE prognosis; oral squamous cell carcinoma; integrin β superfamily members; FAK signaling pathway; integrin αv
ID prognosis; oral squamous cell carcinoma; integrin β superfamily members; FAK signaling pathway; integrin αv
AB Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and β-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive. Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, β1, β3, β5, β6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated. Results: We observed immunohistochemical integrin αV, β1, β6, β8, and FAK expressions in the cell membrane and cytoplasm but not integrin β3 and β5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin β8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed. Conclusion: Our results indicate that pFAK and integrin β8 are prognostic factors for OSCC. Therefore, pFAK- and integrin β8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.
C1 [Sakurai, Shigeru] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Ishida, Yasutaka] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Shintani, Tomoaki] Hiroshima University Hospital, Center of Oral Clinical ExaminationHiroshima, Japan.
[Yamasaki, Sachiko] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Matsui, Kensaku] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Hamana, Tomoaki] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Nobumoto, Tadayoshi] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Yanamoto, Souichi] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
[Hayashido, Yasutaka] Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral OncologyHiroshima, Japan.
RP Hayashido, Y (reprint author), Hiroshima University, Graduate School of Biomedical and Health Science, Department of Oral Oncology, Hiroshima, Japan.
EM ishidayas@hiroshima-u.ac.jp
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611571
EP 1611581
DI 10.3389/pore.2024.1611571
PG 11
ER
PT J
AU Deng, M
Zhang, X
Xu, Ch
Luo, R
Chen, L
Zhou, Y
Hou, Y
AF Deng, Minying
Zhang, Xinyi
Xu, Chen
Luo, Rongkui
Chen, Lingli
Zhou, Yuhong
Hou, Yingyong
TI Clinical and pathological observation of conversion therapy for malignant peritoneal mesothelioma: a case report and literature review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE peritoneal malignant mesothelioma; conversion therapy; clinical pathology; delayed interstitial pneumonitis; PD-L1 expression
ID peritoneal malignant mesothelioma; conversion therapy; clinical pathology; delayed interstitial pneumonitis; PD-L1 expression
AB Background: Malignant mesothelioma (MM) is a tumor originating from the pleura, peritoneum, or pericardial cavity. It is divided into diffuse and localized malignant mesothelioma, with four subtypes in diffuse MM: epithelioid, sarcomatoid, desmoplastic, and biphasic, with biphasic being less common. The onset of this tumor is insidious, and the prognosis is extremely poor in some cases, with a median survival of 6–18 months and no standard treatment options in the past. Aims: We report a case of peritoneal malignant mesothelioma that was successfully treated with transformative therapy. We also review the literature in the hope of providing reference for the treatment and pathological diagnosis of such patients. Methods: The case of the peritoneal malignant mesothelioma was processed and reported in the routine manner for biopsy specimens at different stages. Results and conclusion: We report a case of a malignant tumor originating in the hepatorenal recess, which was diagnosed as biphasic malignant mesothelioma through a biopsy. Immunohistochemical testing showed PDL1 expression. After multidisciplinary discussion, the patient received transformative treatment, including a trial of combined immunotherapy. The tumor significantly shrank, and the patient obtained a chance for curative surgical resection. Microscopic examination showed significant collagenization in the lesion area, with almost no residual tumor. After 19 months of comprehensive treatment, the patient developed multiple fluffy opacities under the pleura of both lungs. Transthoracic core needle biopsy under CT guidance, the pathology showed organizing pneumonia, considering it as delayed interstitial pneumonitis due to immunotherapy based on previous treatment history. Successful comprehensive treatment was achieved for this case of peritoneal malignant mesothelioma, and the patient has been alive without evidence of disease for 33 months, with long-term follow-up. In this process, the pathologist had three opportunities for pathological diagnosis, which required understanding the patient’s medical history, being attentive to the clinical purpose of the specimen, and providing accurate responses to morphological changes at different stages, along with corresponding descriptions and diagnoses to provide effective information for clinical treatment.
C1 [Deng, Minying] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Zhang, Xinyi] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Xu, Chen] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Luo, Rongkui] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Chen, Lingli] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
[Zhou, Yuhong] Fudan University, Zhongshan Hospital, Department of Medical OncologyShanghai, China.
[Hou, Yingyong] Fudan University, Zhongshan Hospital, Department of PathologyShanghai, China.
RP Hou, Y (reprint author), Fudan University, Zhongshan Hospital, Department of Pathology, Shanghai, China.
EM hou.yingyong@zs-hospital.sh.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611577
EP 1611584
DI 10.3389/pore.2023.1611577
PG 8
ER
PT J
AU Moldvay, J
Timar, J
AF Moldvay, Judit
Timar, Jozsef
TI KRASG12C mutant lung adenocarcinoma: unique biology, novel therapies and new challenges
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE KRAS; lung adenocarcinoma; G12C mutation; sotorasib; adagrasib
ID KRAS; lung adenocarcinoma; G12C mutation; sotorasib; adagrasib
AB KRAS mutant lung cancer is the most prevalent molecular subclass of adenocarcinoma (LUAD), which is a heterogenous group depending on the mutation-type which affects not only the function of the oncogene but affects the biological behavior of the cancer as well. Furthermore, KRAS mutation affects radiation sensitivity but leads also to bevacizumab and bisphosphonate resistance as well. It was highly significant that allele specific irreversible inhibitors have been developed for the smoking associated G12C mutant KRAS (sotorasib and adagrasib). Based on trial data both sotorasib and adagrasib obtained conditional approval by FDA for the treatment of previously treated advanced LUAD. Similar to other target therapies, clinical administration of KRASG12C inhibitors (sotorasib and adagrasib) resulted in acquired resistance due to various genetic changes not only in KRAS but in other oncogenes as well. Recent clinical studies are aiming to increase the efficacy of G12C inhibitors by novel combination strategies.
C1 [Moldvay, Judit] National Koranyi Institute of PulmonologyBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM jtimar@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611580
EP 1611588
DI 10.3389/pore.2023.1611580
PG 9
ER
PT J
AU Kovacs,
Trasi, K
Barabas, M
Gal, K
Csiki, E
Sipos, D
Papp, J
Simon, M
AF Kovacs, Arpad
Trasi, Krisztina
Barabas, Marton
Gal, Kristof
Csiki, Emese
Sipos, David
Papp, Judit
Simon, Mihaly
TI LINAC-based SBRT in treating early-stage NSCLC patients— single institution experience and survival data analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE VATS; NSCLC; SBRT; LINAC-based SBRT; early stage
ID VATS; NSCLC; SBRT; LINAC-based SBRT; early stage
AB Aim: This single institute prospective study aimed to evaluate the feasibility of LINAC-based stereotactic body radiotherapy (SBRT) in treating patients with early-stage non-small cell lung cancer (NSLSC). We focused on the survival data with the local and distant control profiles and the cancer- and non-cancerspecific survival. Treatment-related side effects were also collected and analyzed. Methods: Patients with early-stage NSCLC between January 2018 and October 2021 were included in our prospective study; a total of 77 patients receiving LINAC-based SBRT were analyzed. All patients had pretreatment multidisciplinary tumor board decisions on SBRT. The average patient age was 68.8 years (median: 70 years, range: 52–82); 70 patients were in ECOG 0 status (91%), while seven patients were in ECOG 1-2 status (9%). 52% of the patients (40) had histologically verified NSCLC, and the other 48% were verified based on PETCT results. We applied the SBRT scheme 8 x 7.5 Gy for central tumors (74%) or 4 x 12 Gy for peripheral tumors (26%). Results: The mean follow-up time was 25.4 months (median 23, range 18–50). The Kaplan-Meier estimation for overall survival in patients receiving LINAC-based SBRTwas 41.67months.Of the 77 patients treated by SBRT, deathwas reported for 17 patients (9 cases cancer-specific, 8 cases non-cancer specific reason). The mean local tumor control was 34.25months (range 8.4–41), and the mean systemic control was 24.24months (range 7–25). During the treatments, no Grade I-II were reported; in 30 cases, Grade I non-symptomatic treatmentrelated lung fibrosis and two asymptomatic rib fractures were reported. Conclusion: In the treatment of early-stage NSCLC, LINAC-based SBRT can be a feasible alternative to surgery. Although we reported worse OS data in our patient cohort compared to the literature, the higher older average age and the initial worse general condition (ECOG1-2) in our patient cohort appear to be the reason for this difference. With the comparable local control and survival data and the favorable side effect profile, SBRT might be preferable over surgery in selected cases.
C1 [Kovacs, Arpad] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Trasi, Krisztina] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Barabas, Marton] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Gal, Kristof] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Csiki, Emese] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Sipos, David] Pecsi Tudomanyegyetem, Egeszsegtudomanyi Kar, Doktori IskolaPecs, Hungary.
[Papp, Judit] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Simon, Mihaly] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
RP Kovacs, (reprint author), Debreceni Egyetem, Onkologiai Klinika, Sugarterapia Osztaly, Debrecen, Hungary.
EM kovacsarpad@med.unideb.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611589
EP 1611594
DI 10.3389/pore.2024.1611589
PG 6
ER
PT J
AU Kumbrink, J
Demes, MCh
Jeroch, J
Brauninger, A
Hartung, K
Gerstenmaier, U
Marienfeld, R
Hillmer, A
Bohn, N
Lehning, Ch
Ferch, F
Wild, P
Gattenlohner, S
Moller, P
Klauschen, F
Jung, A
AF Kumbrink, Jorg
Demes, Melanie-Christin
Jeroch, Jan
Brauninger, Andreas
Hartung, Kristin
Gerstenmaier, Uwe
Marienfeld, Ralf
Hillmer, Axel
Bohn, Nadine
Lehning, Christina
Ferch, Ferdinand
Wild, Peter
Gattenlohner, Stefan
Moller, Peter
Klauschen, Frederick
Jung, Andreas
TI Development, testing and validation of a targeted NGS-panel for the detection of actionable mutations in lung cancer (NSCLC) using anchored multiplex PCR technology in a multicentric setting
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; targeted therapy; next-generation sequencing panel; anchored multiplex PCR; actionable mutations
ID lung cancer; targeted therapy; next-generation sequencing panel; anchored multiplex PCR; actionable mutations
AB Lung cancer is a paradigm for a genetically driven tumor. A variety of drugs were developed targeting specific biomarkers requiring testing for tumor genetic alterations in relevant biomarkers. Different next-generation sequencing technologies are available for library generation: 1) anchored multiplex-, 2) amplicon based- and 3) hybrid capture-based-PCR. Anchored multiplex PCRbased sequencing was investigated for routine molecular testing within the national Network Genomic Medicine Lung Cancer (nNGM). Four centers applied the anchored multiplex ArcherDX-Variantplex nNGMv2 panel to reanalyze samples pre-tested during routine diagnostics. Data analyses were performed by each center and compiled centrally according to study design. Pre-defined standards were utilized, and panel sensitivity was determined by dilution experiments. nNGMv2 panel sequencing was successful in 98.9% of the samples (N = 90). With default filter settings, all but two potential MET exon 14 skipping variants were identified at similar allele frequencies. Both MET variants were found with an adapted calling filter. Three additional variants (KEAP1, STK11, TP53) were called that were not identified in pre-testing analyses. Only total DNA amount but not a qPCR-based DNA quality score correlated with average coverage. Analysis was successful with a DNA input as low as 6.25 ng. Anchored multiplex PCR-based sequencing (nNGMv2) and a sophisticated user-friendly Archer-Analysis pipeline is a robust and specific technology to detect tumor genetic mutations for precision medicine of lung cancer patients.
C1 [Kumbrink, Jorg] Ludwig Maximilian University of Munich (LMU), Faculty of Medicine, Institute of PathologyMunich, Germany.
[Demes, Melanie-Christin] University Hospital Frankfurt, Dr. Senckenberg Institute of PathologyFrankfurt, Germany.
[Jeroch, Jan] University Hospital Frankfurt, Dr. Senckenberg Institute of PathologyFrankfurt, Germany.
[Brauninger, Andreas] Justus-Liebig-University, Institute for PathologyGiessen, Germany.
[Hartung, Kristin] Justus-Liebig-University, Institute for PathologyGiessen, Germany.
[Gerstenmaier, Uwe] Ulm University, Department of PathologyUlm, Germany.
[Marienfeld, Ralf] Ulm University, Department of PathologyUlm, Germany.
[Hillmer, Axel] University of Cologne Medical School, Institute of PathologyCologne, Germany.
[Bohn, Nadine] ArcherBoulder, CO, USA.
[Lehning, Christina] ArcherBoulder, CO, USA.
[Ferch, Ferdinand] ArcherBoulder, CO, USA.
[Wild, Peter] University Hospital Frankfurt, Dr. Senckenberg Institute of PathologyFrankfurt, Germany.
[Gattenlohner, Stefan] Justus-Liebig-University, Institute for PathologyGiessen, Germany.
[Moller, Peter] Ulm University, Department of PathologyUlm, Germany.
[Klauschen, Frederick] Ludwig Maximilian University of Munich (LMU), Faculty of Medicine, Institute of PathologyMunich, Germany.
[Jung, Andreas] Ludwig Maximilian University of Munich (LMU), Faculty of Medicine, Institute of PathologyMunich, Germany.
RP Kumbrink, J (reprint author), Ludwig Maximilian University of Munich (LMU), Faculty of Medicine, Institute of Pathology, Munich, Germany.
EM joerg.kumbrink@med.uni-muenchen.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611590
EP 1611604
DI 10.3389/pore.2024.1611590
PG 15
ER
PT J
AU Wu, J
Wang, Y
Cheng, Y
Cheng, L
Zhang, L
AF Wu, Jiaxin
Wang, Yuanying
Cheng, Yi
Cheng, Li
Zhang, LuShun
TI Comprehensive landscape and future perspectives of non-coding RNAs in esophageal squamous cell carcinoma, a bibliometric analysis from 2008 to 2023
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE novel biomarker; non-coding RNAs; digestive system cancer; bibliometric analysis; VOSviewer
ID novel biomarker; non-coding RNAs; digestive system cancer; bibliometric analysis; VOSviewer
AB Objectives: Summarize the progress and hot topic evolution of non-coding RNAs (ncRNAs) research in esophageal squamous cell carcinoma (ESCC) in recent years and predict future research directions. Methods: Relevant articles from the Web of Science until 31 October 2023 were obtained. Bibliometric analysis of included articles was performed using software (VOSviewer, CiteSpace, and Bibliometrix). The volume and citation of publications, as well as the country, institution, author, journal, keywords of the articles were used as variables to analyze the research trends and hot spot evolution. Results: 1,118 literature from 2008 to 2023 were retrieved from database, with 25 countries/regions, 793 institutions, 5,426 authors, 261 journals involved. Global cooperation was centered on China, Japan, and the United States. Zhengzhou University, an institution from China, had the highest publication. The most prolific author was Guo Wei, and the most prolific journal was Oncology Letters. Analysis of keywords revealed that the research in this field revolved around the role of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC, mainly including micro RNAs, long non-coding RNAs, and then circular RNAs. Conclusion: Overall, research on ncRNAs in ESCC remains strong. Previous research has mainly focused on the basic research, with a focus on the mechanism of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC. Combining current research with emerging disciplines to further explore its mechanisms of action or shifting the focus of research from preclinical research to clinical research based on diagnosis, treatment, and prognosis, will be the main breakthrough in this field in the future.
C1 [Wu, Jiaxin] Chengdu Medical College, Graduate SchoolChengdu, China.
[Wang, Yuanying] Chengdu Medical College, Graduate SchoolChengdu, China.
[Cheng, Yi] People’s Hospital of Lushan County, Department of RadiologyYa’an, China.
[Cheng, Li] Cheng Du Medical College, Department of Pathology and PathophysiologyChengdu, China.
[Zhang, LuShun] Cheng Du Medical College, Department of Pathology and PathophysiologyChengdu, China.
RP Zhang, L (reprint author), Cheng Du Medical College, Department of Pathology and Pathophysiology, Chengdu, China.
EM zhangls2012@cmc.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611595
EP 1611606
DI 10.3389/pore.2024.1611595
PG 12
ER
PT J
AU Fekete, M
Major, D
Feher, A
Fazekas-Pongor, V
Lehoczki, A
AF Fekete, Monika
Major, David
Feher, Agnes
Fazekas-Pongor, Vince
Lehoczki, Andrea
TI Geroscience and pathology: a new frontier in understanding age-related diseases
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE geroscience; senescence; cancer; cardiovascular disease; ageing
ID geroscience; senescence; cancer; cardiovascular disease; ageing
AB Geroscience, a burgeoning discipline at the intersection of aging and disease, aims to unravel the intricate relationship between the aging process and pathogenesis of age-related diseases. This paper explores the pivotal role played by geroscience in reshaping our understanding of pathology, with a particular focus on age-related diseases. These diseases, spanning cardiovascular and cerebrovascular disorders, malignancies, and neurodegenerative conditions, significantly contribute to the morbidity and mortality of older individuals. We delve into the fundamental cellular and molecular mechanisms underpinning aging, including mitochondrial dysfunction and cellular senescence, and elucidate their profound implications for the pathogenesis of various age-related diseases. Emphasis is placed on the importance of assessing key biomarkers of aging and biological age within the realm of pathology. We also scrutinize the interplay between cellular senescence and cancer biology as a central area of focus, underscoring its paramount significance in contemporary pathological research. Moreover, we shed light on the integration of anti-aging interventions that target fundamental aging processes, such as senolytics, mitochondria-targeted treatments, and interventions that influence epigenetic regulation within the domain of pathology research. In conclusion, the integration of geroscience concepts into pathological research heralds a transformative paradigm shift in our understanding of disease pathogenesis and promises breakthroughs in disease prevention and treatment.
C1 [Fekete, Monika] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Major, David] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Feher, Agnes] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Fazekas-Pongor, Vince] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Lehoczki, Andrea] Semmelweis University, Department of Public HealthBudapest, Hungary.
RP Fazekas-Pongor, V (reprint author), Semmelweis University, Department of Public Health, Budapest, Hungary.
EM pongor.vince@semmelweis.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611623
EP 1611636
DI 10.3389/pore.2024.1611623
PG 14
ER
PT J
AU Sztankovics, D
Moldvai, D
Petovari, G
Danko, T
Szalai, F
Miyaura, R
Varga, V
Nagy, N
Papp, G
Papay, J
Krencz, I
Sebestyen, A
AF Sztankovics, Daniel
Moldvai, Dorottya
Petovari, Gabor
Danko, Titanilla
Szalai, Fatime
Miyaura, Risa
Varga, Viktoria
Nagy, Noemi
Papp, Gergo
Papay, Judit
Krencz, Ildiko
Sebestyen, Anna
TI mTOR hyperactivity and RICTOR amplification as targets for personalized treatments in malignancies
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE mTOR; mTORC2 hyperactivity; RICTOR amplification; Rictor overexpression; malignancies
ID mTOR; mTORC2 hyperactivity; RICTOR amplification; Rictor overexpression; malignancies
AB The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with RICTOR (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies. The activity of mTOR complexes is recommended to be assessed and considered in cancers before mTOR inhibitor therapy, as current firstgeneration mTOR inhibitors (rapamycin and analogs) can be ineffective in the presence of mTORC2 hyperactivity. We have introduced and proposed a marker panel to determine tissue characteristics of mTOR activity in biopsy specimens, patient materials, and cell lines. Ongoing phase trials of new inhibitors and combination therapies are promising in advanced-stage patients selected by genetic alterations, molecular markers, and/or protein expression changes in the mTOR signaling pathway. Hopefully, the summarized results, our findings, and the suggested characterization of mTOR activity will support therapeutic decisions.
C1 [Sztankovics, Daniel] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Moldvai, Dorottya] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Petovari, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Szalai, Fatime] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Miyaura, Risa] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Varga, Viktoria] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Nagy, Noemi] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Papp, Gergo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Papay, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Sebestyen, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM hsebanna@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611643
EP 1611661
DI 10.3389/pore.2024.1611643
PG 19
ER
PT J
AU Molnar, A
Palfi, E
Belak, B
Blasszauer, C
Reibl, D
Lovey, J
AF Molnar, Andrea
Palfi, Erzsebet
Belak, Barbara
Blasszauer, Celia
Reibl, Daniel
Lovey, Jozsef
TI Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE medical nutrition therapy; survival; real -word evidence; persistence of nutrition and survival; head and neck cancer
ID medical nutrition therapy; survival; real -word evidence; persistence of nutrition and survival; head and neck cancer
AB Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients’ nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. Method: The data of this retrospective, analytical, cohort study was collected from electronic healthcare records from the Hungarian National Health Insurance Fund Management. Overall, 38,675 HNC patients’ data of the period between 2012 and 2021 was used. We applied multi-step exclusions to identify patient groups accurately and to avoid biasing factors. Statistical analysis was done by the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: Throughout the investigated period 16,871 (64%) patients received MNT therapy out of 26,253 newly diagnosed patients (≥18 years). In terms of the persistence of MNT, we divided the patients into three groups (1–3; 4–6; ≥7- month duration of MNT). When comparing these groups, we found that patients receiving long-term (≥7 months) MNT had a significantly longer overall survival (p < 0.0001) than those who received MNT for a shorter duration, both in locally advanced and recurrent/metastatic cases. Conclusion: The main outcome of the study is that there is a positive correlation between the persistence of MNT and the overall survival in HNC patients when nutritional intervention lasts several months. It highlights the responsibility of the specialists during the patient journey to use MNT early and to continue its use for as long as it is beneficial to the patients.
C1 [Molnar, Andrea] Semmelweis University, Doctoral School, Health Sciences DivisionBudapest, Hungary.
[Palfi, Erzsebet] Semmelweis University, Doctoral School, Health Sciences DivisionBudapest, Hungary.
[Belak, Barbara] Semmelweis University, Doctoral School, Health Sciences DivisionBudapest, Hungary.
[Blasszauer, Celia] MedicalScan Kft.Budapest, Hungary.
[Reibl, Daniel] MedicalScan Kft.Budapest, Hungary.
[Lovey, Jozsef] Orszagos Onkologiai Intezet, Nemzeti Tumorbiologiai LaboratoriumBudapest, Hungary.
RP Molnar, A (reprint author), Semmelweis University, Doctoral School, Health Sciences Division, Budapest, Hungary.
EM dr.molnarandrea.rd@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611664
EP 1611673
DI 10.3389/pore.2024.1611664
PG 10
ER
PT J
AU Timar, J
Ladanyi, A
Sebestyen, A
Kopper, L
AF Timar, Jozsef
Ladanyi, Andrea
Sebestyen, Anna
Kopper, Laszlo
TI Editorial: Pathology and Oncology Research: addressing publication ethics issues
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Editorial
DE peer review; publication ethics; scientometry; quality control; transparency
ID peer review; publication ethics; scientometry; quality control; transparency
C1 [Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Ladanyi, Andrea] National Institute of OncologyBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kopper, Laszlo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM jtimar@gmail.com
CR Kopper L, Timar J. 25th anniversary of Pathology Oncology Research. Pathol Oncol Res, 2020, 26:1., DOI 10.1007/s12253-020-00795-2
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COPE Council. COPE discussion document. Americas: Predatory Publishing, 2019)., DOI 10.24318/cope.2019.3.6
Kulka J, Cserni G. Editorial: guidelines from the central-eastern European professional consensus statement on breast cancer. Pathol Oncol Res, 2022, 28: 1610587., DOI 10.3389/pore.2022.1610587
Guidelines from the Central-Eastern European Professional Consensus Statement on Breast Cancer. Special issue eBook. Lausanne: Frontiers, 2022). ISBN 978-2-88976-944-5., DOI 10.3389/978-2-88976-944-5
Ryska A. Editorial: liquid biopsy—a great hope or just hype? Pathol Oncol Res, 2023, 29:1611170., DOI 10.3389/pore.2023.1611170
Liquid Biopsy - A Great Hope or Just Hype?. Special issue eBook. Lausanne: Frontiers, 2023). ISBN 978-2-83252-182-3., DOI 10.3389/978-2-83252-182-3
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Pathology and Oncology Research – Editors’ Picks from 2022. Special issue eBook. Lausanne: Frontiers, 2023). ISBN 978-2-83251-901-1., DOI 10.3389/978-2-83251-901-1
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611691
EP 1611692
DI 10.3389/pore.2024.1611691
PG 2
ER
PT J
AU Liu, Y
Chen, Z
Wang, L
Li, B
AF Liu, Yuqing
Chen, Zhenwei
Wang, Lu
Li, Baizhou
TI Intestinal Langerhans cell histiocytosis presenting with symptoms similar to inflammatory bowel disease: a case report
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Langerhans cell histiocytosis; histiocytosis; intestine; infant; case report
ID Langerhans cell histiocytosis; histiocytosis; intestine; infant; case report
AB Background: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder. Case presentation: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment. Conclusion: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.
C1 [Liu, Yuqing] Zhejiang University, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Department of PathologyYiwu, Zhejiang, China.
[Chen, Zhenwei] Zhejiang University, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Department of PathologyYiwu, Zhejiang, China.
[Wang, Lu] Zhejiang University, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Department of PathologyYiwu, Zhejiang, China.
[Li, Baizhou] Zhejiang University, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Department of PathologyYiwu, Zhejiang, China.
RP Li, B (reprint author), Zhejiang University, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Department of Pathology, Yiwu, China.
EM libaizhou@zju.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611705
EP 1611711
DI 10.3389/pore.2024.1611705
PG 7
ER
PT J
AU Csiki, E
Simon, M
Papp, J
Barabas, M
Mikaczo, J
Gal, K
Sipos, D
Kovacs,
AF Csiki, Emese
Simon, Mihaly
Papp, Judit
Barabas, Marton
Mikaczo, Johanna
Gal, Kristof
Sipos, David
Kovacs, Arpad
TI Stereotactic body radiotherapy in lung cancer: a contemporary review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE SBRT; NSCLC; lung cancer; review; radiotherapy
ID SBRT; NSCLC; lung cancer; review; radiotherapy
AB The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in “fit,” operable patients as well, so SBRT would be eligible in place of surgery.
C1 [Csiki, Emese] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Simon, Mihaly] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Papp, Judit] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Barabas, Marton] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Mikaczo, Johanna] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Gal, Kristof] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
[Sipos, David] University of Pecs, Faculty of Health SciencesPecs, Hungary.
[Kovacs, Arpad] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
RP Simon, M (reprint author), Debreceni Egyetem, Onkologiai Klinika, Sugarterapia Osztaly, Debrecen, Hungary.
EM simonm@med.unideb.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611709
EP 1611721
DI 10.3389/pore.2024.1611709
PG 13
ER
PT J
AU Galffy, G
Morocz,
Korompay, R
Hecz, R
Bujdoso, R
Puskas, R
Lovas, T
Gaspar, E
Yahya, K
Kiraly, P
Lohinai, Z
AF Galffy, Gabriella
Morocz, Eva
Korompay, Reka
Hecz, Reka
Bujdoso, Reka
Puskas, Rita
Lovas, Timea
Gaspar, Eszter
Yahya, Kamel
Kiraly, Peter
Lohinai, Zoltan
TI Targeted therapeutic options in early and metastatic NSCLC-overview
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NSCLC; driver oncogenes; targeted therapy; central nervous system efficacy; molecular testing
ID NSCLC; driver oncogenes; targeted therapy; central nervous system efficacy; molecular testing
AB The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in ~15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.
C1 [Galffy, Gabriella] County Hospital of PulmonologyTorokbalint, Hungary.
[Morocz, Eva] County Hospital of PulmonologyTorokbalint, Hungary.
[Korompay, Reka] County Hospital of PulmonologyTorokbalint, Hungary.
[Hecz, Reka] County Hospital of PulmonologyTorokbalint, Hungary.
[Bujdoso, Reka] County Hospital of PulmonologyTorokbalint, Hungary.
[Puskas, Rita] County Hospital of PulmonologyTorokbalint, Hungary.
[Lovas, Timea] County Hospital of PulmonologyTorokbalint, Hungary.
[Gaspar, Eszter] County Hospital of PulmonologyTorokbalint, Hungary.
[Yahya, Kamel] County Hospital of PulmonologyTorokbalint, Hungary.
[Kiraly, Peter] County Hospital of PulmonologyTorokbalint, Hungary.
[Lohinai, Zoltan] County Hospital of PulmonologyTorokbalint, Hungary.
RP Lohinai, Z (reprint author), County Hospital of Pulmonology, Torokbalint, Hungary.
EM lohinai.zoltan@semmelweis.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611715
EP 1611735
DI 10.3389/pore.2024.1611715
PG 21
ER
PT J
AU Editorial Office,
AF Editorial Office,
TI Retraction: High expression of long noncoding RNA HOTAIRM1 is associated with the proliferation and migration in pancreatic ductal adenocarcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB Following publication, the authors contacted the Editorial Office to request the retraction of the cited article, stating that concerns were raised on the PubPeer platform regarding the reuse of certain images. The authors have stated that some of the experiments were conducted by collaboration laboratories and that certain images were mistakenly used.
C1 [Editorial Office, ] Pathology & Oncology ResearchBudapest, Hungary.
RP Editorial Office, (reprint author), Pathology & Oncology Research, Budapest, Hungary.
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611728
EP 1611729
DI 10.3389/pore.2024.1611728
PG 2
ER
PT J
AU Batar, P
Alizadeh, H
Rokszin, Gy
Abonyi-Toth, Zs
Demeter, J
AF Batar, Peter
Alizadeh, Hussain
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Demeter, Judit
TI Corrigendum: Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE chronic myeloid leukemia; real-word evidence; tyrosine kinase inhibitors; treatment outcome; overall survival
ID chronic myeloid leukemia; real-word evidence; tyrosine kinase inhibitors; treatment outcome; overall survival
C1 [Batar, Peter] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Alizadeh, Hussain] University of Pecs, I. Department of Internal MedicinePecs, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Batar, P (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM pbatar@med.unideb.hu
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611758
EP 1611759
DI 10.3389/pore.2024.1611758
PG 2
ER
PT J
AU Editorial Office,
AF Editorial Office,
TI Retraction: MiR-184 retarded the proliferation, invasiveness and migration of glioblastoma cells by repressing stanniocalcin-2
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
C1 [Editorial Office, ] Pathology & Oncology ResearchBudapest, Hungary.
RP Editorial Office, (reprint author), Pathology & Oncology Research, Budapest, Hungary.
EM editorialoffice@por-journal.com
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2024
VL 30
IS 1
BP 1611767
EP 1611767
DI 10.3389/pore.2024.1611767
PG 1
ER
PT J
AU Jakab, A
Patai,
Darvas, M
Tormassi-Bely, K
Micsik, T
AF Jakab, Anna
Patai, V. Arpad
Darvas, Monika
Tormassi-Bely, Karolina
Micsik, Tamas
TI Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; consensus molecular subtypes; tumor microenvironment (TME); tumor-stroma ratio; systemic inflammation
ID colorectal cancer; consensus molecular subtypes; tumor microenvironment (TME); tumor-stroma ratio; systemic inflammation
AB Introduction: Colorectal carcinomas (CRC) are one of the most frequent malignancies worldwide. Based on gene expression profile analysis, CRCs can be classified into four distinct subtypes also known as the consensus molecular subtypes (CMS), which predict biological behaviour. Besides CMS, several other aspects of tumor microenvironment (TME) and systemic inflammatory response (SIR) influence the outcome of CRC patients. TME and inflammation have important role in the immune (CMS1) and mesenchymal (CMS4) subtypes, however, the relationship between these and systemic inflammation has not been assessed yet. Our objective was to evaluate the connection between CMS, TME and SIR, and to analyze the correlation between these markers and routinely used tumor markers, such as CEA (Carcinoembryonic Antigen) and CA19-9 (Carbohydrate Antigen 19-9). Methods: FFPE (Formalin Fixed Paraffin Embedded) samples of 185 CRC patients were collected. TME was described using tumor-stroma ratio (TSR), Klintrup-Makinen (KM) grade, and Glasgow Microenvironment Score (GMS). CMS classification was performed on tissue microarray using MLH1, PMS2, MSH2 and MSH6, and pan-cytokeratin, CDX2, FRMD6, HTR2B and ZEB1 immunohistochemical stains. Pre-operative tumor marker levels and inflammatory markers [C-reactive protein - CRP, albumin, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC)] and patient history were retrieved using MedSolution database. Results: Amongst TME-markers, TSR correlated most consistently with adverse clinicopathological features (p < 0.001) and overall survival (p < 0.001). Elevated CRP and modified Glasgow Prognostic Score (mGPS) were associated with worse outcome and aggressive phenotype, similarly to tumor markers CEA and CA19-9. Stroma–Tumor Marker score (STM score), a new combined score of CA19-9 and TSR delivered the second best prognostication after mGPS. Furthermore, CMS4 showed association with TSR and several laboratory markers (albumin and platelet derived factors), but not with other SIR descriptors. CMS did not show any association with CEA and CA19-9 tumor markers. Conclusion: More routinely available TME, SIR and tumor markers alone and in combination deliver reliable prognostic data for choosing the patients with higher risk for propagation. CMS4 is linked with high TSR and poor prognosis, but in overall, CMS-classification showed only limited effect on SIR- and tumor-markers.
C1 [Jakab, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Patai, V. Arpad] Semmelweis University, Interdisciplinary Gastroenterology Working GroupBudapest, Hungary.
[Darvas, Monika] Semmelweis University, Interdisciplinary Gastroenterology Working GroupBudapest, Hungary.
[Tormassi-Bely, Karolina] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Micsik, Tamas] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Jakab, A (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM annajakab272@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611574
EP 1611593
DI 10.3389/pore.2024.1611574
PG 20
ER
PT J
AU Grayson, K
Greenlee, J
Himmel, L
Hapach, L
Reinhart-King, C
King, M
AF Grayson, A. Korie
Greenlee, D. Joshua
Himmel, E. Lauren
Hapach, A. Lauren
Reinhart-King, A. Cynthia
King, R. Michael
TI Spatial distribution of tumor-associated macrophages in an orthotopic prostate cancer mouse model
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor-associated macrophages; TRAIL; liposomes; prostate cancer; pathologic analysis
ID tumor-associated macrophages; TRAIL; liposomes; prostate cancer; pathologic analysis
AB Mounting evidence suggests that the immune landscape within prostate tumors influences progression, metastasis, treatment response, and patient outcomes. In this study, we investigated the spatial density of innate immune cell populations within NOD.SCID orthotopic prostate cancer xenografts following microinjection of human DU145 prostate cancer cells. Our laboratory has previously developed nanoscale liposomes that attach to leukocytes via conjugated E-selectin (ES) and kill cancer cells via TNF-related apoptosis inducing ligand (TRAIL). Immunohistochemistry (IHC) staining was performed on tumor samples to identify and quantify leukocyte infiltration for different periods of tumor growth and E-selectin/TRAIL (EST) liposome treatments. We examined the spatialtemporal dynamics of three different immune cell types infiltrating tumors using QuPath image analysis software. IHC staining revealed that F4/80+ tumor-associated macrophages (TAMs) were the most abundant immune cells in all groups, irrespective of time or treatment. The density of TAMs decreased over the course of tumor growth and decreased in response to EST liposome treatments. Intratumoral versus marginal analysis showed a greater presence of TAMs in the marginal regions at 3 weeks of tumor growth which became more evenly distributed over time and in tumors treated with EST liposomes. TUNEL staining indicated that EST liposomes significantly increased cell apoptosis in treated tumors. Additionally, confocal microscopy identified liposome-coated TAMs in both the core and periphery of tumors, highlighting the ability of liposomes to infiltrate tumors by “piggybacking” on macrophages. The results of this study indicate that TAMs represent the majority of innate immune cells within NOD.SCID orthotopic prostate tumors, and spatial density varieswidely as a function of tumor size, duration of tumor growth, and treatment of EST liposomes.
C1 [Grayson, A. Korie] Vanderbilt University, Department of Biomedical EngineeringNashville, TN, USA.
[Greenlee, D. Joshua] Vanderbilt University, Department of Biomedical EngineeringNashville, TN, USA.
[Himmel, E. Lauren] Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology, Translational Pathology Shared ResourceNashville, TN, USA.
[Hapach, A. Lauren] Vanderbilt University, Department of Biomedical EngineeringNashville, TN, USA.
[Reinhart-King, A. Cynthia] Vanderbilt University, Department of Biomedical EngineeringNashville, TN, USA.
[King, R. Michael] Vanderbilt University, Department of Biomedical EngineeringNashville, TN, USA.
RP King, M (reprint author), Vanderbilt University, Department of Biomedical Engineering, Nashville, USA.
EM mike.king@rice.edu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611586
EP 1611598
DI 10.3389/pore.2024.1611586
PG 13
ER
PT J
AU Krencz, I
Sztankovics, D
Sebestyen, A
Papay, J
Danko, T
Moldvai, D
Lutz, E
Khoor, A
AF Krencz, Ildiko
Sztankovics, Daniel
Sebestyen, Anna
Papay, Judit
Danko, Titanilla
Moldvai, Dorottya
Lutz, Elmar
Khoor, Andras
TI RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE RICTOR amplification; Rictor expression; mTORC2; PD-L1; lung squamous cell carcinoma
ID RICTOR amplification; Rictor expression; mTORC2; PD-L1; lung squamous cell carcinoma
AB RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.
C1 [Krencz, Ildiko] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sztankovics, Daniel] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sebestyen, Anna] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Papay, Judit] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Danko, Titanilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Moldvai, Dorottya] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Lutz, Elmar] Mayo Clinic, Department of Laboratory Medicine and PathologyJacksonville, FL, USA.
[Khoor, Andras] Mayo Clinic, Department of Laboratory Medicine and PathologyJacksonville, FL, USA.
RP Khoor, A (reprint author), Mayo Clinic, Department of Laboratory Medicine and Pathology, Jacksonville, USA.
EM khoor.andras@mayo.edu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611593
EP 1611602
DI 10.3389/pore.2024.1611593
PG 10
ER
PT J
AU Kerpel-Fronius, A
Bogos, K
AF Kerpel-Fronius, Anna
Bogos, Krisztina
TI HUNCHEST projects—advancing low-dose CT lung cancer screening in Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lung cancer; screening; LDCT; pulmonary nodules; implementation
ID lung cancer; screening; LDCT; pulmonary nodules; implementation
AB Lung cancer, the leading cause of malignancy-related deaths worldwide, demands proactive measures to mitigate its impact. Low-dose computer tomography (LDCT) has emerged as a promising tool for secondary prevention through lung cancer screening (LCS). The HUNCHEST study, inspired by the success of international trials, including the National Lung Cancer Screening Trial and the Dutch NELSON study, embarked on the first LDCT-based LCS program in Hungary. The initiative assessed the screening efficiency, incorporating lung function tests and exploring the interplay between lung cancer and chronic obstructive pulmonary disease (COPD). Building upon this foundation, an implementation trial involving 18 Hungarian centers supported by the Ministry of Human Capacities demonstrated the feasibility of LCS within a multicentric framework. These centers, equipped with radiology capabilities, collaborated with multidisciplinary oncology teams, ensuring optimal patient pathways. However, a critical challenge remained the patient recruitment. To address this, the HUNCHEST 3 project, initiated in 2023, seeks to engage general practitioners (GPs) to reach out to eligible patients within a municipality collective of 60 thousand inhabitants. The project’s ultimate success is contingent upon the willingness of eligible individuals to undergo LDCT scans. In conclusion, the HUNCHEST program represents a crucial step in advancing lung cancer screening in Hungary. With a focus on efficiency, multidisciplinary collaboration, and innovative patient recruitment strategies, it endeavors to contribute to the reduction of lung cancer mortality and serve as a blueprint for potential nationwide LCS programs.
C1 [Kerpel-Fronius, Anna] Orszagos Koranyi Tbc es Pulmonologiai Intezet, Radiologiai OsztalyBudapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute for Pulmonology, DirectorBudapest, Hungary.
RP Kerpel-Fronius, A (reprint author), Orszagos Koranyi Tbc es Pulmonologiai Intezet, Radiologiai Osztaly, Budapest, Hungary.
EM kerpel.anna@koranyi.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611635
EP 1611642
DI 10.3389/pore.2024.1611635
PG 8
ER
PT J
AU Szakallas, N
Bartak, B
Valcz, G
Nagy, Zs
Takacs, I
Molnar, B
AF Szakallas, Nikolett
Bartak, K. Barbara
Valcz, Gabor
Nagy, B. Zsofia
Takacs, Istvan
Molnar, Bela
TI Can long-read sequencing tackle the barriers, which the next-generation could not? A review
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE sequencing; short-read; long-read; bioinformatics; DNA
ID sequencing; short-read; long-read; bioinformatics; DNA
AB The large-scale heterogeneity of genetic diseases necessitated the deeper examination of nucleotide sequence alterations enhancing the discovery of new targeted drug attack points. The appearance of new sequencing techniques was essential to get more interpretable genomic data. In contrast to the previous short-reads, longer lengths can provide a better insight into the potential health threatening genetic abnormalities. Longreads offer more accurate variant identification and genome assembly methods, indicating advances in nucleotide deflect-related studies. In this review, we introduce the historical background of sequencing technologies and show their benefits and limits, as well. Furthermore, we highlight the differences between short- and long-read approaches, including their unique advances and difficulties in methodologies and evaluation. Additionally, we provide a detailed description of the corresponding bioinformatics and the current applications.
C1 [Szakallas, Nikolett] Eotvos Lorand University, Faculty of Science, Department of Biological PhysicsBudapest, Hungary.
[Bartak, K. Barbara] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Valcz, Gabor] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Nagy, B. Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Takacs, Istvan] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Molnar, Bela] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Szakallas, N (reprint author), Eotvos Lorand University, Faculty of Science, Department of Biological Physics, Budapest, Hungary.
EM szakallasn3@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611676
EP 1611687
DI 10.3389/pore.2024.1611676
PG 12
ER
PT J
AU Han, Z
Yang, F
Wang, F
Zheng, H
Chen, X
Meng, H
Li, F
AF Han, Zesen
Yang, Fujun
Wang, Fang
Zheng, Huayu
Chen, Xiujian
Meng, Hongyu
Li, Fenglei
TI Advances in combined neuroendocrine carcinoma of lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE small cell neuroendocrine carcinoma; large cell neuroendocrine carcinoma; adenocarcinoma; squamous cell carcinoma; lung cancer
ID small cell neuroendocrine carcinoma; large cell neuroendocrine carcinoma; adenocarcinoma; squamous cell carcinoma; lung cancer
AB Lung cancer incidence and mortality rates are increasing worldwide, posing a significant public health challenge and an immense burden to affected families. Lung cancer encompasses distinct subtypes, namely, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). In clinical investigations, researchers have observed that neuroendocrine tumors can be classified into four types: typical carcinoid, atypical carcinoid, small-cell carcinoma, and largecell neuroendocrine carcinoma based on their unique features. However, there exist combined forms of neuroendocrine cancer. This study focuses specifically on combined pulmonary carcinomas with a neuroendocrine component. In this comprehensive review article, the authors provide an overview of combined lung cancers and present two pathological images to visually depict these distinctive subtypes.
C1 [Han, Zesen] Hua Country People’s HospitalAnyang, Henan, China.
[Yang, Fujun] Henan University of Science and Technology, Sanmenxia Central Hospital, Department of Medical OncologySanmenxia, China.
[Wang, Fang] Hua Country People’s HospitalAnyang, Henan, China.
[Zheng, Huayu] Hua Country People’s HospitalAnyang, Henan, China.
[Chen, Xiujian] Hua Country People’s HospitalAnyang, Henan, China.
[Meng, Hongyu] Hua Country People’s HospitalAnyang, Henan, China.
[Li, Fenglei] Hua Country People’s HospitalAnyang, Henan, China.
RP Han, Z (reprint author), Hua Country People’s Hospital, Anyang, China.
EM hanzesen908@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611693
EP 1611698
DI 10.3389/pore.2024.1611693
PG 6
ER
PT J
AU Orosz, Zs
Kovacs,
AF Orosz, Zsuzsanna
Kovacs, Arpad
TI The role of chemoradiotherapy and immunotherapy in stage III NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE locally advanced; NSCLC; chemoradiotherapy; immunotherapy; durvalumab
ID locally advanced; NSCLC; chemoradiotherapy; immunotherapy; durvalumab
AB Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable nonsmall lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PDL1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.
C1 [Orosz, Zsuzsanna] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Kovacs, Arpad] Debreceni Egyetem, Onkologiai Klinika, Sugarterapia OsztalyDebrecen, Hungary.
RP Orosz, Zs (reprint author), University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, Debrecen, Hungary.
EM zsuzsa.orosz@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611716
EP 1611721
DI 10.3389/pore.2024.1611716
PG 6
ER
PT J
AU Nadorvari, M
Lotz, G
Kulka, J
Kiss, A
Timar, J
AF Nadorvari, L. Maja
Lotz, Gabor
Kulka, Janina
Kiss, Andras
Timar, Jozsef
TI Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE mismatch repair deficiency; microsatellite instability; immunohistochemistry; molecular testing; cancer
ID mismatch repair deficiency; microsatellite instability; immunohistochemistry; molecular testing; cancer
AB Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.
C1 [Nadorvari, L. Maja] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Lotz, Gabor] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Timar, J (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM jtimar@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611719
EP 1611730
DI 10.3389/pore.2024.1611719
PG 12
ER
PT J
AU Cegledi, A
Batai,
Dolgos, J
Fekete, M
Gopcsa, L
Kiraly, V
Lakatos, G
Nagy, Gy
Szemlaky, Zs
Varkonyi, A
Vilimi, B
Mikala, G
Bodo, I
AF Cegledi, Andrea
Batai, Arpad
Dolgos, Janos
Fekete, Monika
Gopcsa, Laszlo
Kiraly, Viktoria
Lakatos, Gergely
Nagy, Gyorgy
Szemlaky, Zsuzsanna
Varkonyi, Andrea
Vilimi, Beata
Mikala, Gabor
Bodo, Imre
TI Case Report: Effective management of adalimumab-induced acquired hemophilia A with the CyDRI protocol
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE adalimumab; acquired hemophilia A; bleeding disorder; immunosuppression; rheumatoid arthritis
ID adalimumab; acquired hemophilia A; bleeding disorder; immunosuppression; rheumatoid arthritis
AB Introduction: Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the emergence of inhibitors that specifically target coagulation Factor VIII, frequently resulting in severe bleeding episodes. Methods: We conducted a retrospective analysis of the medical records of a 68-year-old male patient who presented with adalimumabinduced AHA. Results: The patient received adalimumab, a tumor necrosis factor inhibitor antibody, as part of his treatment for rheumatoid arthritis. The patient’s clinical journey, characterized by intense bleeding and coagulopathy, was effectively managed with the application of recombinant Factor VIIa (rFVIIa) and the CyDRi protocol. Discussion: The case emphasizes the importance of prompt coagulation assessment in patients with bleeding symptoms receiving disease-modifying therapy for rheumatoid arthritis that includes adalimumab therapy, considering the rare yet life-threatening nature of AHA. Additionally, this report provides an extensive review of the existing literature on druginduced AHA, with a special emphasis on cases linked to immunomodulatory medications. Through this two-pronged approach, our report aims to enhance understanding and awareness of this severe complication among healthcare providers, promoting timely diagnosis and intervention.
C1 [Cegledi, Andrea] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Batai, Arpad] Fejer County Szent Gyorgy HospitalSzekesfehervar, Hungary.
[Dolgos, Janos] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Fekete, Monika] Semmelweis University, Department of Public HealthBudapest, Hungary.
[Gopcsa, Laszlo] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Kiraly, Viktoria] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Lakatos, Gergely] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Nagy, Gyorgy] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Szemlaky, Zsuzsanna] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Varkonyi, Andrea] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Vilimi, Beata] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Mikala, Gabor] Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios OsztalyBudapest, Hungary.
[Bodo, Imre] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
RP Cegledi, A (reprint author), Del-pesti Centrumkorhaz – Orszagos Hematologiai es Infektologiai Intezet, Hematologiai es Ossejt-transzplantacios Osztaly, Budapest, Hungary.
EM ceglediandi@freemail.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611720
EP 1611727
DI 10.3389/pore.2024.1611720
PG 8
ER
PT J
AU Toth, JL
Mokanszki, A
Mehes, G
AF Toth, Jozsef Laszlo
Mokanszki, Attila
Mehes, Gabor
TI The rapidly changing field of predictive biomarkers of non-small cell lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NSCLC; driver oncogenes; immune checkpoint inhibitor; gene fusion; biomarker
ID NSCLC; driver oncogenes; immune checkpoint inhibitor; gene fusion; biomarker
AB Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.
C1 [Toth, Jozsef Laszlo] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Mokanszki, Attila] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
RP Toth, JL (reprint author), University of Debrecen, Faculty of Medicine, Department of Pathology, Debrecen, Hungary.
EM tothlasz@med.unideb.hu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611733
EP 1611759
DI 10.3389/pore.2024.1611733
PG 27
ER
PT J
AU Li, H
Zheng, L
Zhong, G
Yu, X
Zhang, X
Chen, L
Chen, X
AF Li, Houqiang
Zheng, Lanqing
Zhong, Guodong
Yu, Xunbin
Zhang, Xia
Chen, Linying
Chen, Xin
TI Gastric epithelial neoplasm of fundic-gland mucosa lineage: representative of the low atypia differentiated gastric tumor and Ki67 may help in their identification
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gastric cancer; gastric adenocarcinoma of fundic-gland type; gastric adenocarcinoma of fundic-gland mucosa type; oxyntic gland adenoma; low-grade differentiated gastric tumors
ID gastric cancer; gastric adenocarcinoma of fundic-gland type; gastric adenocarcinoma of fundic-gland mucosa type; oxyntic gland adenoma; low-grade differentiated gastric tumors
AB Background: Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the cause, classification, and clinicopathological features of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods: 37 cases diagnosed with GEN-FGMLs were included in this study. H&E-stained slides were reviewed and clinicopathological parameters were recorded. Immunohistochemical staining was conducted for MUC2, MUC5AC, MUC6, CD10, CD56, synaptophysin, chromograninA, p53, Ki67, pepsinogen-I, H+/K+-ATPase and Desmin. Results: The patients’ ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between OGA, GA-FG, and GA-FGM. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. These cells resembled fundic gland cells. None of the OGA invaded the submucosal layer. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Non-atrophic gastritis was observed in more than half of the background mucosa. All cases were diffusely positive for MUC6 and pepsinogen-I on immunohistochemistry. H+/K+-ATPase staining was negative or showed a scattered pattern in most cases. MUC5AC was expressed on the surface of GA-FGMs. p53 was focally expressed and the Ki67 index was low (1%–20%). Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p < 0.05) and had larger sizes (p < 0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p < 0.0001). Specimens with Ki-67 proliferation indices >2.5% and size >4.5mm are more likely to be diagnosed with GA-FG and GAFGM than OGA. Conclusion: GEN-FGMLs are group of well-differentiated gastric tumors with favourable biological behaviours, low cellular atypia, and low proliferation. Immunohistochemistry is critical for confirming diagnosis. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GENFGML. Pathologists and endoscopists should be cautious to prevent misdiagnosis and overtreatment, especially in biopsy specimens.
C1 [Li, Houqiang] Fujian Medical University, Shengli Clinical Medical CollegeFuzhou, Fujian, China.
[Zheng, Lanqing] Fujian Medical University, Shengli Clinical Medical CollegeFuzhou, Fujian, China.
[Zhong, Guodong] Fujian Traditional Chinese Medical University, The Second Affiliated HospitalFuzhou, Fujian, China.
[Yu, Xunbin] Fujian Medical University, Shengli Clinical Medical CollegeFuzhou, Fujian, China.
[Zhang, Xia] Fujian Medical University, Shengli Clinical Medical CollegeFuzhou, Fujian, China.
[Chen, Linying] Fujian Medical University, The First Affiliated HospitalFuzhou, Fujian, China.
[Chen, Xin] Fujian Medical University, Shengli Clinical Medical CollegeFuzhou, Fujian, China.
RP Li, H (reprint author), Fujian Medical University, Shengli Clinical Medical College, Fuzhou, China.
EM docli254@126.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611734
EP 1611743
DI 10.3389/pore.2024.1611734
PG 10
ER
PT J
AU Deme, D
Tamaskovics, FB
Jammoul, N
Kovacs, S
Kayode, OE
Grice, J
Telekes, A
AF Deme, Daniel
Tamaskovics, Ferenc Balint
Jammoul, Nizar
Kovacs, Sandor
Kayode, Oladunjoye Emmanuel
Grice, W. James
Telekes, Andras
TI Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE breast cancer; pathological characteristics; OncotypeDX; recurrence score; observation oriented modeling
ID breast cancer; pathological characteristics; OncotypeDX; recurrence score; observation oriented modeling
AB Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS). Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients. Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki- 67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes). Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.
C1 [Deme, Daniel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Tamaskovics, Ferenc Balint] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Jammoul, Nizar] Szent Lazar Megyei Korhaz, Patologiai OsztalySalgotarjan, Hungary.
[Kovacs, Sandor] University of Debrecen, Department of Economical and Financial MathematicsDebrecen, Hungary.
[Kayode, Oladunjoye Emmanuel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Grice, W. James] Oklahoma State University, Department of PsychologyStillwater, OK, USA.
[Telekes, Andras] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611735
EP 1611761
DI 10.3389/pore.2024.1611735
PG 27
ER
PT J
AU Mihalekne Fur, G
Nemes, K
Mago,
Beno, A
Topolcsanyi, P
Moldvay, J
Pongor, L
AF Mihalekne Fur, Gabriella
Nemes, Kolos
Mago, Eva
Beno, A. Alexandra
Topolcsanyi, Petronella
Moldvay, Judit
Pongor, S. Lorinc
TI Applied models and molecular characteristics of small cell lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE SCLC; drug response; ctDNA; liquid biopsy; databases
ID SCLC; drug response; ctDNA; liquid biopsy; databases
AB Small cell lung cancer (SCLC) is a highly aggressive type of cancer frequently diagnosed with metastatic spread, rendering it surgically unresectable for the majority of patients. Although initial responses to platinum-based therapies are often observed, SCLC invariably relapses within months, frequently developing drug-resistance ultimately contributing to short overall survival rates. Recently, SCLC research aimed to elucidate the dynamic changes in the genetic and epigenetic landscape. These have revealed distinct subtypes of SCLC, each characterized by unique molecular signatures. The recent understanding of the molecular heterogeneity of SCLC has opened up potential avenues for precision medicine, enabling the development of targeted therapeutic strategies. In this review, we delve into the applied models and computational approaches that have been instrumental in the identification of promising drug candidates. We also explore the emerging molecular diagnostic tools that hold the potential to transform clinical practice and patient care.
C1 [Mihalekne Fur, Gabriella] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
[Nemes, Kolos] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
[Mago, Eva] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
[Beno, A. Alexandra] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
[Topolcsanyi, Petronella] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
[Moldvay, Judit] Szentgyorgyi A. University, Pulmonology ClinicSzeged, Hungary.
[Pongor, S. Lorinc] Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core GroupSzeged, Hungary.
RP Pongor, L (reprint author), Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Cancer Genomics and Epigenetics Core Group, Szeged, Hungary.
EM lorinc.pongor@hcemm.eu
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611743
EP 1611755
DI 10.3389/pore.2024.1611743
PG 13
ER
PT J
AU Kaval, G
Kartal, GDM
Azamat, S
Cingoz, E
Ertas, G
Karaman, S
Kurtuldu, B
Keskin, M
Berker, N
Karabulut, S
Oral, NE
Sakin, DN
AF Kaval, Gizem
Kartal, Gulbiz Dagoglu Merve
Azamat, Sena
Cingoz, Eda
Ertas, Gokhan
Karaman, Sule
Kurtuldu, Basak
Keskin, Metin
Berker, Neslihan
Karabulut, Senem
Oral, Nezih Ethem
Sakin, Dagoglu Nergiz
TI Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE rectal cancer; watch and wait; radiomics; radiotherapy; pathological complete response ratio
ID rectal cancer; watch and wait; radiomics; radiotherapy; pathological complete response ratio
AB Purpose: Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV. Methods and materials: Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machinelearning models. Results: CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively. Conclusion: Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.
C1 [Kaval, Gizem] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
[Kartal, Gulbiz Dagoglu Merve] Cerrahpasa Medical School, Istanbul University, Department of RadiologyIstanbul, Turkey.
[Azamat, Sena] Cam and Sakura City Hospital, Department of RadiologyIstanbul, Turkey.
[Cingoz, Eda] Bagcilar Training and Research Hospital, Department of RadiologyIstanbul, Turkey.
[Ertas, Gokhan] Yeditepe University, Department of Biomedical EngineeringIstanbul, Turkey.
[Karaman, Sule] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
[Kurtuldu, Basak] Hackalibaba Hospital, Department of EmergencyTrabzon, Turkey.
[Keskin, Metin] Istanbul Faculty of Medicine, Istanbul University, Department of SurgeryIstanbul, Turkey.
[Berker, Neslihan] Istanbul Medical Faculty, Department of PathologyIstanbul, Turkey.
[Karabulut, Senem] Istanbul Medical Faculty, Istanbul University, Oncology InstituteIstanbul, Turkey.
[Oral, Nezih Ethem] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
[Sakin, Dagoglu Nergiz] Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation OncologyIstanbul, Turkey.
RP Kaval, G (reprint author), Istanbul University, Istanbul Medicine Faculty, Institute of Oncology, Department of Radiation Oncology, Istanbul, Turkey.
EM gizemkaval1@istanbul.edu.tr
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611744
EP 1611752
DI 10.3389/pore.2024.1611744
PG 9
ER
PT J
AU Galffy, G
Szabo, TG
Tamasi, L
Muller, V
Moldvay, J
Sarosi, V
Kerpel-Fronius, A
Kardos, T
Csada, E
Papai-Szekely, Zs
Szasz, Z
Kiraly, Zs
Hodi, G
Kovacs, Zs
Balogh,
Kovacs, AK
Darida, M
Buga, V
Rokszin, Gy
Abonyi-Toth, Zs
Kiss, Z
Voko, Z
Bogos, K
AF Galffy, Gabriella
Szabo, Tamas Geza
Tamasi, Lilla
Muller, Veronika
Moldvay, Judit
Sarosi, Veronika
Kerpel-Fronius, Anna
Kardos, Tamas
Csada, Edit
Papai-Szekely, Zsolt
Szasz, Zoltan
Kiraly, Zsolt
Hodi, Gabor
Kovacs, Zsuzsanna
Balogh, Eva
Kovacs, Andrea Krisztina
Darida, Miklos
Buga, Viktoria
Rokszin, Gyorgy
Abonyi-Toth, Zsolt
Kiss, Zoltan
Voko, Zoltan
Bogos, Krisztina
TI Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung cancer; incidence; mortality; COVID-19; Hungary
ID lung cancer; incidence; mortality; COVID-19; Hungary
AB Objective: Hungary has repeatedly been shown to have the highest cancerrelated mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017–2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patientswere diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%–4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40–49 and 50–59) featured the largest improvement, butwomen aged 60–79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50–59 age group (both sexes). Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60–79, the incidence of lung cancer has risen, requiring more attention in the near future.
C1 [Galffy, Gabriella] County Hospital of PulmonologyTorokbalint, Hungary.
[Szabo, Tamas Geza] MSD Pharma Hungary Kft.Budapest, Hungary.
[Tamasi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Moldvay, Judit] National Koranyi Institute for TB and Pulmonology, Department of PulmonologyBudapest, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of MedicinePecs, Hungary.
[Kerpel-Fronius, Anna] Orszagos Koranyi Tbc es Pulmonologiai Intezet, Radiologiai OsztalyBudapest, Hungary.
[Kardos, Tamas] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Csada, Edit] Szentgyorgyi A. University, Pulmonology ClinicSzeged, Hungary.
[Papai-Szekely, Zsolt] Fejer County Szent Gyorgy HospitalSzekesfehervar, Hungary.
[Szasz, Zoltan] Petz Aladar Megyei Oktato Korhaz, PulmonologiaGyor, Hungary.
[Kiraly, Zsolt] Veszprem Megyei Onkormanyzat TudogyogyintezeteFarkasgyepu, Hungary.
[Hodi, Gabor] MSD Pharma Hungary Kft.Budapest, Hungary.
[Kovacs, Zsuzsanna] MSD Pharma Hungary Kft.Budapest, Hungary.
[Balogh, Eva] MSD Pharma Hungary Kft.Budapest, Hungary.
[Kovacs, Andrea Krisztina] MSD Pharma Hungary Kft.Budapest, Hungary.
[Darida, Miklos] MSD Pharma Hungary Kft.Budapest, Hungary.
[Buga, Viktoria] MSD Pharma Hungary Kft.Budapest, Hungary.
[Rokszin, Gyorgy] RxTarget LtdSzolnok, Hungary.
[Abonyi-Toth, Zsolt] RxTarget LtdSzolnok, Hungary.
[Kiss, Zoltan] MSD Pharma Hungary Kft.Budapest, Hungary.
[Voko, Zoltan] Semmelweis University, Center for Health Technology AssessmentBudapest, Hungary.
[Bogos, Krisztina] National Koranyi Institute of PulmonologyBudapest, Hungary.
RP Kiss, Z (reprint author), MSD Pharma Hungary Kft., Budapest, Hungary.
EM zoltan_kiss2@merck.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611754
EP 1611764
DI 10.3389/pore.2024.1611754
PG 11
ER
PT J
AU Antal, G
Zsigmond, A
Till,
Orsi, E
Szanto, I
Buki, G
Kereskai, L
Herbert, Zs
Hadzsiev, K
Bene, J
AF Antal, Greta
Zsigmond, Anna
Till, Agnes
Orsi, Eniko
Szanto, Ildiko
Buki, Gergely
Kereskai, Laszlo
Herbert, Zsuzsanna
Hadzsiev, Kinga
Bene, Judit
TI Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Gardner syndrome; APC gene; osteoma; dental abnormalities; WES
ID Gardner syndrome; APC gene; osteoma; dental abnormalities; WES
AB Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%– 70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget’s disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient’s DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients’ chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
C1 [Antal, Greta] University of Pecs, Department of Oral and Maxillofacial SurgeryPecs, Hungary.
[Zsigmond, Anna] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Till, Agnes] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Orsi, Eniko] University of Pecs, Department of Oral and Maxillofacial SurgeryPecs, Hungary.
[Szanto, Ildiko] University of Pecs, Department of Oral and Maxillofacial SurgeryPecs, Hungary.
[Buki, Gergely] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Kereskai, Laszlo] University of Pecs, Department of PathologyPecs, Hungary.
[Herbert, Zsuzsanna] PTE KK, Radiologiai KlinikaPecs, Hungary.
[Hadzsiev, Kinga] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Bene, Judit] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
RP Bene, J (reprint author), University of Pecs, Department of Medical Genetics and Child Development, Pecs, Hungary.
EM bene.judit@pte.hu
CR Oliveira MR, Rodrigues WC, Gabrielli MF, Gabrielli MA, Onofre MA, Filho VA. Gardner syndrome with unusual maxillofacial manifestation. J Craniofac Surg, 2016, 27(5):1253–5., DOI 10.1097/SCS. 0000000000002741
Salti L, Rasse M, Al-Ouf K. Maxillofacial Radiographic study of Gardner’s syndrome presenting with odontogenic myxoma: a rare case report. Stomatologija, 2018, 20(2):59–64.
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611768
EP 1611773
DI 10.3389/pore.2024.1611768
PG 6
ER
PT J
AU Wang, Y
Lei, Y
Zheng, D
Yang, Y
Luo, L
Li, J
Xie, X
AF Wang, Yi
Lei, Yu
Zheng, Delai
Yang, Yanhui
Luo, Lei
Li, Ji
Xie, Xiaoyang
TI Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lung immune prognostic index; non-small cell lung cancer; immune checkpoint inhibitor; prognosis; meta-analysis
ID lung immune prognostic index; non-small cell lung cancer; immune checkpoint inhibitor; prognosis; meta-analysis
AB Background and Purpose: Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs). Methods: Several electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted. Results: In thismeta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09–2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64–1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1–2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0–1 and 2 vs. 1) showed similar results. Conclusion: LIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis.
C1 [Wang, Yi] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Lei, Yu] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Zheng, Delai] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Yang, Yanhui] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Luo, Lei] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Li, Ji] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
[Xie, Xiaoyang] Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic SurgeryNeijiang, Sichuan, China.
RP Xie, X (reprint author), Neijiang Affiliated Hospital of Chongqing Medical University, The First People’s Hospital of Neijiang, Department of Thoracic Surgery, Neijiang, China.
EM 13990559066@163.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611773
EP 1611785
DI 10.3389/pore.2024.1611773
PG 13
ER
PT J
AU Papai-Szekely, Zs
Grmela, G
Sarosi, V
AF Papai-Szekely, Zsolt
Grmela, Gabor
Sarosi, Veronika
TI Novel diagnostic processes and challenges in bronchoscopy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE diagnostic bronchoscopy; respiratory medicine; endobronchial ultrasound; virtual bronchoscopy; autofluorescence bronchoscopy
ID diagnostic bronchoscopy; respiratory medicine; endobronchial ultrasound; virtual bronchoscopy; autofluorescence bronchoscopy
AB Diagnostic bronchoscopy is a minimally invasive procedure that plays a crucial role in the diagnosis and management of various respiratory conditions. This paper explores the advancements in technology that have revolutionized the field and focuses on the new diagnostic procedures in bronchoscopy that have emerged in recent years. These innovative techniques have expanded the diagnostic capabilities of bronchoscopy, allowing for more accurate and comprehensive evaluation of respiratory conditions. This paper will also discuss the challenges in the diagnostic process with bronchoscope.
C1 [Papai-Szekely, Zsolt] Szent Gyorgy University Teaching Hospital of Fejer County, Department of PulmonologySzekesfehervar, Hungary.
[Grmela, Gabor] Szent Gyorgy University Teaching Hospital of Fejer County, Department of PulmonologySzekesfehervar, Hungary.
[Sarosi, Veronika] University of Pecs, Faculty of Medicine, Department of PulmonologyPecs, Hungary.
RP Papai-Szekely, Zs (reprint author), Szent Gyorgy University Teaching Hospital of Fejer County, Department of Pulmonology, Szekesfehervar, Hungary.
EM zsoltpapai@yahoo.com
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Lam B, Wong MP, Fung SL, Lam DC, Wong PC, Mok TY, et al. The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer. Eur Respir J, 2006, 28(5):915–9., DOI 10.1183/09031936.06.00131405
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611774
EP 1611782
DI 10.3389/pore.2024.1611774
PG 9
ER
PT J
AU Editorial Office,
AF Editorial Office,
TI Retraction: Case report: A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB A Retraction of the Case Report Article Case report: A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma by Zhang L, Yuan P, Cao Q, Mu J, Ying J and Guo C (2023). Pathol. Oncol. Res. 29:1611204. doi: 10.3389/pore.2023.1611204
C1 [Editorial Office, ] Pathology & Oncology ResearchBudapest, Hungary.
RP Editorial Office, (reprint author), Pathology & Oncology Research, Budapest, Hungary.
EM editorialoffice@por-journal.com
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611784
EP 1611784
DI 10.3389/pore.2024.1611784
PG 1
ER
PT J
AU Imanbayev, N
Iztleuov, Y
Kamyshanskiy, Y
Zhumasheva, A
AF Imanbayev, M. Nauryzbay
Iztleuov, M. Yerbolat
Kamyshanskiy, K. Yevgeniy
Zhumasheva, V. Aigul
TI Diagnostic and prognostic significance of keloid-like collagen remodeling patterns in the extracellular matrix of colorectal cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE colorectal cancer; intermediate desmoplastic reaction; keloid-like collagen; desmoplastic reaction; extracellular matrix of colorectal cancer
ID colorectal cancer; intermediate desmoplastic reaction; keloid-like collagen; desmoplastic reaction; extracellular matrix of colorectal cancer
AB Background: The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable stromal heterogeneity, including both small amounts of keloid-like collagen (KC) in the fibrotic stroma and thick tufts of KC circumferentially surrounding cancer nests and occupying most of the fields of view. The present study aimed to evaluate the diagnostic and prognostic significance of KC histophenotyping with a quantitative visual assessment of its presence in the stroma of the invasive margin of TNM (The “tumor-node-metastasis” classification) stage II/III colorectal cancer (CRC). Methods and results: 175 resected tumors from patients with TNM stage II/III CRC were examined. Keloid-like collagen was assessed according to Ueno H. criteria. KC was assessed at the primary tumor invasive margin using Hematoxylin & Eosin and Masson’s trichrome staining. The cut-off point for KC was examined using “the best cutoff approach by log-rank test.” Using a cutoff point of 30%, we histologically divided fibrous stroma in the invasive area into two groups: “type A”—KC ≤ 0.3 and “type B”—KC>0.3. Type A stroma was observed in 48% of patients, type B—in 52%. The association between collagen amount and 5-year recurrence-free survival (5-RFS) was assessed using Cox regression analysis. Kaplan-Meier analysis and logrank tests were used to assess the significance of survival analysis. Analysis of categorical variables showed that increased KC in CRC stroma predicted adverse outcomes for 5-RFS (hazard ratio [HR] = 3.143, 95%, confidence interval [CI] = 1.643–6.012, p = 0.001). Moreover, in Kaplan-Meier analysis, the log-rank test showed that type B exhibited worse 5- RFS than type A (p = 0.000). Conclusion: KC is an independent predictor of 5-year overall and RFS in patients with TNM stage II/III CRC treated with surgery, with worse survival rates when the amount of KC increases by >30%.
C1 [Imanbayev, M. Nauryzbay] West Kazakhstan Marat Ospanov Medical University, Department of OncologyAktobe, Kazakhstan.
[Iztleuov, M. Yerbolat] West Kazakhstan Marat Ospanov Medical University, Department of RadiologyAktobe, Kazakhstan.
[Kamyshanskiy, K. Yevgeniy] Karaganda Medical University, Department of PathologyKaraganda, Kazakhstan.
[Zhumasheva, V. Aigul] Medical Centre of West Kazakhstan Marat Ospanov Medical University, Department of PathomorphologyAktobe, Kazakhstan.
RP Imanbayev, N (reprint author), West Kazakhstan Marat Ospanov Medical University, Department of Oncology, Aktobe, Kazakhstan.
EM dr.imanbayev@gmail.com
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611789
EP 1611798
DI 10.3389/pore.2024.1611789
PG 10
ER
PT J
AU Della Corte, L
Ascione, M
Bifulco, G
AF Della Corte, Luigi
Ascione, Mario
Bifulco, Giuseppe
TI Modified clock mapping biopsy sec. Della Corte-Bifulco in the preoperative assessment of excisional surgery for vulvar Paget’s disease
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE gynecological cancer; extramammary Paget’s disease of the vulva; vulvar malignant lesion; preoperative biopsy; new technique
ID gynecological cancer; extramammary Paget’s disease of the vulva; vulvar malignant lesion; preoperative biopsy; new technique
AB We have developed a biopsy technique aimed at preoperative evaluating the extent of Paget’s vulvar disease in order to plan subsequent radical vulvar surgery. The aim is to find all possible lesion sites that are not visible macroscopically, to obtain a clear evaluation of the disease spread and to tailor the radical surgical procedure to remove even microscopic lesions, avoiding recurrences and excessively destructive surgery, adopting as conservative an approach as possible. We used this procedure for the first time to establish the radicality of the surgical intervention in a 68-year-old patient initially suffering from a single invasive vulvar Paget’s lesion.
C1 [Della Corte, Luigi] University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and DentistryNaples, Italy.
[Ascione, Mario] University of Naples Federico II, Department of Public HealthNaples, Italy.
[Bifulco, Giuseppe] University of Naples Federico II, Department of Public HealthNaples, Italy.
RP Della Corte, L (reprint author), University of Naples Federico II, School of Medicine, Department of Neuroscience, Reproductive Sciences and Dentistry, Naples, Italy.
EM dellacorte.luigi25@gmail.com
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McDaniel B, Brown F, Crane JS. Extramammary Paget disease. Treasure Island, FL, USA: StatPearls Publishing, 2022).
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Kato T, Fujimoto N, Fujii N, Tanaka T. Mapping biopsy with punch biopsies to determine surgical margin in extramammary Paget’s disease. J Dermatol, 2013, 40:968–72., DOI 10.1111/1346-8138.12347
GarganeseG, Anchora LP, Fragomeni SM, MantovaniG, Santoro A, Gentileschi S, et al. “Clock mapping” prior to excisional surgery in vulvar Paget’s disease: tailoring the surgical plan. Arch Gynecol Obstet, 2022, 306:473–80., DOI 10.1007/s00404-022-06408-4
NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611803
EP 1611806
DI 10.3389/pore.2024.1611803
PG 4
ER
PT J
AU Jeon, H
Gor, R
D’Aiello, A
Stiles, B
Illei, P
Halmos, B
AF Jeon, Hyein
Gor, Rajvi
D’Aiello, Angelica
Stiles, Brendon
Illei, B. Peter
Halmos, Balazs
TI Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NSCLC; perioperative; neoadjuvant; adjuvant; lung cancer
ID NSCLC; perioperative; neoadjuvant; adjuvant; lung cancer
AB The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced longterm survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.
C1 [Jeon, Hyein] Montefiore Medical Center/Albert Einstein College of Medicine, Department of OncologyBronx, NY, USA.
[Gor, Rajvi] Jacobi Medical Center, Department of MedicineBronx, NY, USA.
[D’Aiello, Angelica] Montefiore Medical Center/Albert Einstein College of Medicine, Department of OncologyBronx, NY, USA.
[Stiles, Brendon] Albert Einstein College of Medicine, Montefiore Medical Center, Department of Cardiothoracic and Vascular SurgeryBronx, NY, USA.
[Illei, B. Peter] Johns Hopkins School of Medicine, Department of PathologyBaltimore, MD, USA.
[Halmos, Balazs] Montefiore Medical Center/Albert Einstein College of Medicine, Department of OncologyBronx, NY, USA.
RP Halmos, B (reprint author), Montefiore Medical Center/Albert Einstein College of Medicine, Department of Oncology, Bronx, USA.
EM bahalmos@montefiore.org
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NR 2
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD APR
PY 2024
VL 30
IS 2
BP 1611817
EP 1611830
DI 10.3389/pore.2024.1611817
PG 14
ER
PT J
AU Lieber, A
Makai, A
Orosz, Zs
Kardos, T
Isaac, JS
Tornyi, I
Bittner, N
AF Lieber, Attila
Makai, Attila
Orosz, Zsuzsanna
Kardos, Tamas
Isaac, Joe Susil
Tornyi, Ilona
Bittner, Nora
TI The role of immunotherapy in early-stage and metastatic NSCLC
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE NSCLC; PD-(L)1; ICI; perioperative; metastatic
ID NSCLC; PD-(L)1; ICI; perioperative; metastatic
AB In the past decade we have seen new advances and thus remarkable progress in the therapeutic options for non-small cell lung cancer (NSCLC). Among cytostatic therapies with new approaches in molecularly targeted therapies, we see new developments in a wide range of applications for immunotherapies. In this review we discuss the new potential modalities for the use of immune checkpoint inhibitors (ICIs) in the frontlines, including in early-stage (perioperative) and metastatic settings. The perioperative use of ICIs in both neoadjuvant and adjuvant settings may show benefits for patients. In earlystage NSCLC (from stage IIB and above) a multimodality approach is recommended as the gold standard for the treatment. After surgical resection platinum-based adjuvant chemotherapy has been the standard of care for many years. Based on the benefit of disease-free survival, the approval of adjuvant atezolizumab and adjuvant pembrolizumab was a significant breakthrough. In the metastatic setting, the use of immune checkpoint inhibitors with chemotherapy, regardless of PD-L1 expression or ICI alone (PD-L1 expression equal to or greater than 50%) also improves overall survival and progression-free survival.
C1 [Lieber, Attila] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Makai, Attila] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Orosz, Zsuzsanna] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Kardos, Tamas] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Isaac, Joe Susil] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Tornyi, Ilona] University of Debrecen Medical and Health Science Center, Department of Pulmonary MedicineDebrecen, Hungary.
[Bittner, Nora] National Koranyi Institute of PulmonologyBudapest, Hungary.
RP Lieber, A (reprint author), University of Debrecen Medical and Health Science Center, Department of Pulmonary Medicine, Debrecen, Hungary.
EM lieber.attila@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611713
EP 1611729
DI 10.3389/pore.2024.1611713
PG 17
ER
PT J
AU Lalic, N
Bojovic, M
Bursac, D
Bokan, D
Krstic, V
Kuhajda, I
Parapid, B
Tomic, S
Sipka, A
AF Lalic, Nensi
Bojovic, Marko
Bursac, Daliborka
Bokan, Darijo
Krstic, Ceriman Vesna
Kuhajda, Ivan
Parapid, Biljana
Tomic, Sanja
Sipka, Aleksandar
TI The efficacy outcomes in non-small cell lung cancer patients treated with PD axis inhibitor agents - a population-based study of the Vojvodina region
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE lung carcinoma; immune checkpoint inhibitors; immunotherapy; PD-L1 receptor; pembrolizumab
ID lung carcinoma; immune checkpoint inhibitors; immunotherapy; PD-L1 receptor; pembrolizumab
AB Background: By 2021, the FDA approved the use of the drugs pembrolizumab and atezolizumab in the first-line treatment of patients with high positivity of programmed death ligand-1 (PD-L1) in locally advanced and metastatic nonsmall- cell-lung cancer (NSCLC). This approval was the result of statistically significant evidence from international, multicentric clinical studies that all reported increasing progression-free survival (PFS) and overall survival (OS) in these patients. Methods: In our study, we reported the demographic and clinical characteristics of 79 patients diagnosed with NSCLC with expression of PDL1 ≥50% from January 2019 to December 2022 at the Institute for Pulmonary Diseases of Vojvodina, who received pembrolizumab therapy as the first-line treatment. Patients were divided according to the histological type of lung cancer as adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of the lung. In 52 of the 79 patients, PFS and in 32 of them overall survival (censored OS) was shown according to the histological type of tumor, the tumor proportion score (TPS) of PDL-1 expression, and the metastatic status within the Tumor Nodes Metastasis (TNM) disease classification. Independent factors of death outcome were shown by multivariable proportional hazard regression analysis. Results: The study included 79 patients diagnosed with NSCLC with an expression of PD-L1 ≥50%, 50 (63.3%) patients with ADC, and 29 (36.7%) patients with SCC, whose 55 (69.6%) PDL-1 expression was obtained from broncho biopsy (BB). The majority of patients, 49 (62%), had a TPS PD-L1 score of 51%–79%. Median, PFS for adenocarcinoma was 22 months and censored OS was 27 months, while for squamous cell carcinoma, median PFS was 12 months, and censored OS was 21 months. M1b disease stage, which was the most common in patients, had a PFS of 16 months and a censored OS of 18 months. Conclusion: Pembrolizumab monotherapy in patients with NSCLC in the fourth stage of the disease and with the positivity of the immune checkpoint protein TPS PD-L1 above 50% represents a safe therapy that allows a satisfactory period without disease progression and overall survival with acceptable treatment complications.
C1 [Lalic, Nensi] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Bojovic, Marko] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Bursac, Daliborka] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Bokan, Darijo] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Krstic, Ceriman Vesna] University of Belgrade, Faculty of MedicineBelgrade, Serbia.
[Kuhajda, Ivan] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Parapid, Biljana] University of Belgrade, Faculty of MedicineBelgrade, Serbia.
[Tomic, Sanja] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
[Sipka, Aleksandar] University of Novi Sad, Medical Faculty Novi SadNovi Sad, Serbia.
RP Bojovic, M (reprint author), University of Novi Sad, Medical Faculty Novi Sad, Novi Sad, Serbia.
EM marko.bojovic@mf.uns.ac.rs
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611717
EP 1611728
DI 10.3389/pore.2024.1611717
PG 12
ER
PT J
AU Kishikawa, S
Kondo, A
Yao, T
Saito, T
AF Kishikawa, Satsuki
Kondo, Akihide
Yao, Takashi
Saito, Tsuyoshi
TI Case report: A mesenchymal chondrosarcoma with alternative HEY1::NCOA2 fusions in the sella turcica
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE mesenchymal chondrosarcoma; intracranial mesenchymal chondrosarcoma; CNS sarcoma; HEY1::NCOA2; sella turcica
ID mesenchymal chondrosarcoma; intracranial mesenchymal chondrosarcoma; CNS sarcoma; HEY1::NCOA2; sella turcica
AB Introduction: Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma that occurs at widespread anatomical locations, such as bone, soft tissue, and intracranial sites. The central nervous system (CNS) is one of the most common origins of extraosseous MCS. However, alternative HEY1::NCOA2 fusions have not been reported in this tumor. Case report: We report a case of intracranial MCS with HEY1::NCOA2 rearrangement. A 52-year-old woman presented with a 15-mm calcified mass around the sella turcica. She initially underwent transsphenoidal surgery for tumor resection and then additional resections for five local recurrences over 5 years. Histologically, the tumor was composed of small round to spindle-shaped cells admixed with well-differentiated hyaline cartilaginous islands. A hemangiopericytoma-like vascular pattern and small sinusoid-like vessels were also observed. RNA sequencing using RNA extracted from formalin-fixed paraffin-embedded samples from the last operation revealed two alternative variants of the HEY1::NCOA2 fusion: HEY1(ex4):: NCOA2 (ex13) and HEY1(ex4)::NCOA2(ex14). Both variants were confirmed as in-frame fusions using reverse transcription-polymerase chain reaction. Discussion: Cartilaginous components were often not apparent during the recurrences. In addition to the non-typical pathological finding, the correct diagnosis was hampered by the poor RNA quality of the surgical specimens and non-specific STAT6 nuclear staining. Conclusion: This is the first reported case of intracranial MCS with an alternative HEY1::NCOA2 fusion.
C1 [Kishikawa, Satsuki] Juntendo University, Graduate School of Medicine, Department of Human PathologyTokyo, Japan.
[Kondo, Akihide] Juntendo University School of Medicine, Department of PathologyTokyo, Japan.
[Yao, Takashi] Juntendo University, Graduate School of Medicine, Department of Human PathologyTokyo, Japan.
[Saito, Tsuyoshi] Juntendo University, Graduate School of Medicine, Department of Human PathologyTokyo, Japan.
RP Saito, T (reprint author), Juntendo University, Graduate School of Medicine, Department of Human Pathology, Tokyo, Japan.
EM tysaitou@juntendo.ac.jp
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611730
EP 1611735
DI 10.3389/pore.2024.1611730
PG 6
ER
PT J
AU Marton, A
Veres, BK
Erdodi, F
Udvardy, M
Illes,
Rejto, L
AF Marton, Adrienn
Veres, Beata Katalin
Erdodi, Ferenc
Udvardy, Miklos
Illes, Arpad
Rejto, Laszlo
TI The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE acute myeloid leukemia; retinoblastoma; AKT; ERK; protein phosphorylation
ID acute myeloid leukemia; retinoblastoma; AKT; ERK; protein phosphorylation
AB Signaling pathways of Retinoblastoma (Rb) protein, Akt-kinase, and Erk-kinase (extracellular signal-regulated kinase) have an important role in the pathogenesis of acute myeloid leukemia. Constitutive activation of these proteins by phosphorylation contributes to cell survival by regulation of cell cycle, proliferation and proapoptotic signaling processes. According to previous data phosphorylated forms of these proteins represent a worse outcome for cancer patients. We investigated the presence of phosphorylated Rb (P-Rb), Akt (P-Akt) and Erk (P-Erk) proteins by Western blot technique using phospho-specific antibodies in bone marrow or peripheral blood samples of 69 AML patients, 36 patients with myelodysplastic syndrome (MDS) and 10 healthy volunteers. Expression level of PTEN (Phosphatase and tensin homolog) and PHLPP (PH domain and leucine-rich repeat Protein Phosphatase) phosphatases, the negative regulators of Akt kinase pathway were also examined. We tested the effect of these proteins on survival and on the correlation with known prognostic features in AML. We found 46.3% of AML patients had detectable P-Rb, 34.7% had P-Akt and 28.9% had P-Erk protein. 66.1% of patients expressing PTEN, 38.9% PHLPP, 37.2% both PTEN and PHLPP and 32.2% neither PTEN nor PHLPP phosphatases. Compared to nucleophosmin mutation (NPMc) negative samples P-Erk was significantly less in nucleophosmin mutated patients, P-Rb was significantly less in patients’ group with more than 30 G/L peripheral leukocyte count by diagnosis. PHLPP was significantly present in FAB type M5. The expression of P-Rb represented significant better overall survival (OS), while P-Akt represented significantly worse event-free survival (EFS) in unfavorable cytogenetics patients. The presence of both PHLPP and PTEN phosphatases contributes to better OS and EFS, although the differences were not statistically significant. We confirmed significant positive correlation between P-Akt and PHLPP. Assessing the phosphorylation of Rb, Akt and Erk may define a subgroup of AML patients who would benefit especially from new targeted treatment options complemented the standard chemotherapy, and it may contribute to monitoring remission, relapse or progression of AML.
C1 [Marton, Adrienn] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Veres, Beata Katalin] MEDYAG Kft, Laboratory of Cellular TherapyDebrecen, Hungary.
[Erdodi, Ferenc] University of Debrecen, Faculty of Medicine, Department of Medical ChemistryDebrecen, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Rejto, Laszlo] Szabolcs-Szatmar-Bereg County Josa Andras Hospital, Department of HaematologyNyiregyhaza, Hungary.
RP Marton, A (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM martonadika@gmail.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611747
EP 1611765
DI 10.3389/pore.2024.1611747
PG 19
ER
PT J
AU Brugos, B
Simon, Zs
Mehes, G
Illes,
Pfliegler, Gy
AF Brugos, Boglarka
Simon, Zsofia
Mehes, Gabor
Illes, Arpad
Pfliegler, Gyorgy
TI Diagnostic challenges in patients with Castleman disease, a single center experience from Hungary
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE unicentric Castleman disease; multicentric Castleman disease; interleukin-6; siltuximab; rituximab
ID unicentric Castleman disease; multicentric Castleman disease; interleukin-6; siltuximab; rituximab
AB Castleman disease is a rare and atypical lymphoproliferative disorder characterized by diverse clinicalmanifestations. It has both unicentric andmulticentric forms, the latter with further subdivisions, i.e., human herpesvirus 8-associated and idiopathic forms. The diagnosis ofCastleman disease is often delayed, as it is rare, and because it shares clinical features with different autoimmune, inflammatory, and malignant lymphoproliferative disorders. The first-line treatment in unicentric form is mainly surgical, while in idiopathic Castleman disease, anti-interleukin-6 treatment is the therapy of choice. In virus-associated diseases, antiretroviral therapy and rituximab are recommended. In Hungary, only a few cases of Castleman disease have been published. This report presents our two decades of experience in the challenging diagnosis and management of this rare disorder, most properly underdiagnosed in Hungary. We provide insights into seven unicentric and five idiopathic multicentric Castleman disease cases, the latter ones especially highlighting the diagnostic and therapeutic challenges due to the variable and unique clinical features both of patients and diseases, e.g., bronchiolitis obliterans, stage IV diabetic renal failure, anti-HBc positivity, siltuximab treatment period, respectively.
C1 [Brugos, Boglarka] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Simon, Zsofia] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Mehes, Gabor] University of Debrecen, Faculty of Medicine, Department of PathologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Pfliegler, Gyorgy] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Brugos, B (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM brugosb@med.unideb.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611785
EP 1611794
DI 10.3389/pore.2024.1611785
PG 10
ER
PT J
AU Cakir, U
Balogh, P
Ferenczik, A
Brodszky, V
Krenacs, T
Karpati, S
Sardy, M
Hollo, P
Fabian, M
AF Cakir, Ugur
Balogh, Petra
Ferenczik, Aniko
Brodszky, Valentin
Krenacs, Tibor
Karpati, Sarolta
Sardy, Miklos
Hollo, Peter
Fabian, Melinda
TI G protein-coupled estrogen receptor 1 and collagen XVII endodomain expression in human cutaneous melanomas: can they serve as prognostic factors?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE estrogen receptor; collagen xvii; prognostic factors; immunohistochemistry; prognosis
ID estrogen receptor; collagen xvii; prognostic factors; immunohistochemistry; prognosis
AB Melanoma incidence is increasing globally. Although novel therapies have improved the survival of primary melanoma patients over the past decade, the overall survival rate for metastatic melanoma remains low. In addition to traditional prognostic factors such as Breslow thickness, ulceration, and mitotic rate, novel genetic and molecular markers have been investigated. In our study, we analyzed the expression of G-protein coupled estrogen receptor 1 (GPER1) and the endodomain of collagen XVII (COL17) in relation to clinicopathological factors in primary cutaneous melanomas with known lymph node status in both sexes, using immunohistochemistry. We found, that GPER1 expression correlated with favorable clinicopathological factors, including lower Breslow thickness, lower mitotic rate and absence of ulceration. In contrast, COL17 expression was associated with poor prognostic features, such as higher tumor thickness, higher mitotic rate, presence of ulceration and presence of regression. Melanomas positive for both GPER1 and COL17 had significantly lower mean Breslow thickness and mitotic rate compared to cases positive for COL17 only. Our data indicate that GPER1 and COL17 proteins may be of potential prognostic value in primary cutaneous melanomas.
C1 [Cakir, Ugur] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Balogh, Petra] University Hospitals Birmingham, Queen Elizabeth Hospital, Cellular Pathology DepartmentBirmingham, UK.
[Ferenczik, Aniko] Corvinus University of Budapest, Doctoral School of Economics, Business and InformaticsBudapest, Hungary.
[Brodszky, Valentin] Corvinus University of Budapest, Institute of Social and Political Sciences, Department of Health PolicyBudapest, Hungary.
[Krenacs, Tibor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Karpati, Sarolta] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Sardy, Miklos] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Hollo, Peter] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
[Fabian, Melinda] Semmelweis University, Department of Dermatology, Venereology and DermatooncologyBudapest, Hungary.
RP Cakir, U (reprint author), Semmelweis University, Department of Dermatology, Venereology and Dermatooncology, Budapest, Hungary.
EM cakir.ugur@semmelweis.hu
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PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611809
EP 1611820
DI 10.3389/pore.2024.1611809
PG 12
ER
PT J
AU Plander, M
Kanyasi, M
Szendrei, T
Skrapits, J
Timar, B
AF Plander, Mark
Kanyasi, Maria
Szendrei, Tamas
Skrapits, Judit
Timar, Botond
TI Flow cytometry in the differential diagnosis of myelodysplastic neoplasm with low blasts and cytopenia of other causes
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE flow cytometry; myelodysplastic neoplasms; low blasts; differential diagnosis; accuracy
ID flow cytometry; myelodysplastic neoplasms; low blasts; differential diagnosis; accuracy
AB Background: Myelodysplastic neoplasms (MDS) are characterized by cytopenia, morphologic dysplasia, and genetic abnormalities. Multiparameter flow cytometry (FCM) is recommended in the diagnostic work-up of suspected MDS, but alone is not sufficient to establish the diagnosis. Our aim was to investigate the diagnostic power of FCM in a heterogeneous population of patients with cytopenia, excluding cases with increased blast count. Methods: We analyzed bone marrow samples from 179 patients with cytopenia (58 MDS, 121 non-MDS) using a standardized 8-color FCM method. We evaluated the sensitivity, specificity, and accuracy of several simple diagnostic approaches, including Ogata score, extended Ogata score, the WHO and ELN iMDSFlow recommended “3 aberrations in two cell compartments method,” and the combination of the Ogata score and “3 aberrations in two cell compartments method.” The patients were followed until the diagnosis was confirmed, with a median follow-up of 2 months (range 0.2–27). Results: The combination of Ogata score and “3 aberrations in two cell compartments method” achieved the highest diagnostic accuracy (78%) with sensitivity and specificity 61% and 86%, respectively. When using only the “3 aberrations in two cell compartments method,” the accuracy was 77% with a sensitivity of 72% and a specificity of 79%. The most frequently observed etiologies among the false positive cases were substrate deficiencies, inflammation/infection, or toxic effects. MDS can be excluded in all these cases after a thorough clinical evaluation and a relatively short follow-up. Conclusion: FCM remains an important but supplementary part in an integrated diagnostic process of MDS with low blasts. The combination of the Ogata score and the “3 aberrations in two cell compartments method” slightly improves accuracy compared to the detection of “3 aberrations in twocell compartments method” alone.
C1 [Plander, Mark] Vas County Markusovszky Hospital, Department of HematologySzombathely, Hungary.
[Kanyasi, Maria] Markusovszky County Hospital, Central LaboratorySzombathely, Hungary.
[Szendrei, Tamas] Vas County Markusovszky Hospital, Department of HematologySzombathely, Hungary.
[Skrapits, Judit] Markusovszky County Hospital, Central LaboratorySzombathely, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Plander, M (reprint author), Vas County Markusovszky Hospital, Department of Hematology, Szombathely, Hungary.
EM planderm@yahoo.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611811
EP 1611818
DI 10.3389/pore.2024.1611811
PG 8
ER
PT J
AU Barati, L
Maasz, A
Miko, A
Bercesi,
Al Kalbani, S
Bene, J
Kovacs, S
Mangel, L
Hadzsiev, K
AF Barati, Laszlo
Maasz, Anita
Miko, Alexandra
Bercesi, Eva
Al Kalbani, Sultan
Bene, Judit
Kovacs, Sebestyen
Mangel, Laszlo
Hadzsiev, Kinga
TI Molecular genetic investigation of hereditary breast and ovarian cancer patients in the Southern Transdanubian region: widening the mutation spectrum and searching for new pathogenic variants using next-generation methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HBOC; new generation sequencing; multigene panel testing; BRCA1; BRCA2
ID HBOC; new generation sequencing; multigene panel testing; BRCA1; BRCA2
AB Hereditary breast and ovarian cancer is a well-known genetic condition, inherited mainly in an autosomal dominant way, which elevates the risk of developing malignancies at a young age in heterozygous carriers. Advances in new generation sequencing have enabled medical professionals to determine whether a patient is harbouring mutations in moderate- or high penetrance susceptibility genes. We conducted a retrospective analysis among 275 patients who underwent genetic counselling and multigene panel testing for hereditary breast and ovarian cancer syndrome in our department. From these patients 74.5% (205/275) were affected by some type of malignancy, while the remaining 25.5% (70/275) had a positive family history of different cancers, suggesting a genetic predisposition. These tests confirmed a genetic variant in 29.8% and 28.6% of these patient groups respectively. The results also mirrored our general knowledge concerning the genetic background of hereditary breast and ovarian cancer, as variants in either one of the BRCA1 and BRCA2 genes proved to be the most common cause among our patients with 41.5%. Our test also detected a novel mutation in the CDH1 gene and three patients with double heterozygosity in two different susceptibility genes. This study demonstrates the relevance of genetic counselling and non-BRCA gene sequencing among cancer patients and patients who fulfil the criteria for genetic testing, while also providing important details about the genetic profile of Hungarian patients.
C1 [Barati, Laszlo] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Miko, Alexandra] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Bercesi, Eva] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Al Kalbani, Sultan] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Bene, Judit] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Kovacs, Sebestyen] University of Pecs, Department of UrologyPecs, Hungary.
[Mangel, Laszlo] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Hadzsiev, Kinga] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
RP Barati, L (reprint author), University of Pecs, Department of Medical Genetics and Child Development, Pecs, Hungary.
EM barati.laszlo@pte.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611813
EP 1611824
DI 10.3389/pore.2024.1611813
PG 12
ER
PT J
AU Barati, L
Maasz, A
Miko, A
Bercesi,
Al Kalbani, S
Bene, J
Kovacs, S
Mangel, L
Hadzsiev, K
AF Barati, Laszlo
Maasz, Anita
Miko, Alexandra
Bercesi, Eva
Al Kalbani, Sultan
Bene, Judit
Kovacs, Sebestyen
Mangel, Laszlo
Hadzsiev, Kinga
TI Molecular genetic investigation of hereditary breast and ovarian cancer patients in the Southern Transdanubian region: widening the mutation spectrum and searching for new pathogenic variants using next-generation methods
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HBOC; new generation sequencing; multigene panel testing; BRCA1; BRCA2
ID HBOC; new generation sequencing; multigene panel testing; BRCA1; BRCA2
AB Hereditary breast and ovarian cancer is a well-known genetic condition, inherited mainly in an autosomal dominant way, which elevates the risk of developing malignancies at a young age in heterozygous carriers. Advances in new generation sequencing have enabled medical professionals to determine whether a patient is harbouring mutations in moderate- or high penetrance susceptibility genes. We conducted a retrospective analysis among 275 patients who underwent genetic counselling and multigene panel testing for hereditary breast and ovarian cancer syndrome in our department. From these patients 74.5% (205/275) were affected by some type of malignancy, while the remaining 25.5% (70/275) had a positive family history of different cancers, suggesting a genetic predisposition. These tests confirmed a genetic variant in 29.8% and 28.6% of these patient groups respectively. The results also mirrored our general knowledge concerning the genetic background of hereditary breast and ovarian cancer, as variants in either one of the BRCA1 and BRCA2 genes proved to be the most common cause among our patients with 41.5%. Our test also detected a novel mutation in the CDH1 gene and three patients with double heterozygosity in two different susceptibility genes. This study demonstrates the relevance of genetic counselling and non-BRCA gene sequencing among cancer patients and patients who fulfil the criteria for genetic testing, while also providing important details about the genetic profile of Hungarian patients.
C1 [Barati, Laszlo] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Maasz, Anita] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Miko, Alexandra] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Bercesi, Eva] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Al Kalbani, Sultan] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Bene, Judit] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
[Kovacs, Sebestyen] University of Pecs, Department of UrologyPecs, Hungary.
[Mangel, Laszlo] University of Pecs, Oncotherapy InstitutePecs, Hungary.
[Hadzsiev, Kinga] University of Pecs, Department of Medical Genetics and Child DevelopmentPecs, Hungary.
RP Barati, L (reprint author), University of Pecs, Department of Medical Genetics and Child Development, Pecs, Hungary.
EM barati.laszlo@pte.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611814
EP 1611825
DI 10.3389/pore.2024.1611813
PG 12
ER
PT J
AU Csontos, A
Nemeth, D
Szako, L
Berke, G
Sindler, LD
Berki, D
Papp, Cs
Hegyi, P
Vereczkei, A
Papp, A
AF Csontos, Armand
Nemeth, David
Szako, Lajos
Berke, Gergo
Sindler, Lili Dora
Berki, David
Papp, Csenge
Hegyi, Peter
Vereczkei, Andras
Papp, Andras
TI Intraoperative pyloric drainage is unnecessary during esophagectomies: a meta-analysis and systematic review of randomized controlled trials
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE esophageal cancer; esophagectomy; esophageal surgery; pyloroplasty; minimal invasive
ID esophageal cancer; esophagectomy; esophageal surgery; pyloroplasty; minimal invasive
AB Objective: The topic of this meta-analysis is the comparison of gastric conduit esophageal reconstructions with or without pyloroplasty. Background: Surgical procedures, especially minimal invasive esophagectomy (MIE) can be a curative treatment in the early stages of esophageal cancer. Previously, intraoperative pyloroplasty was routinely performed, but nowadays it became debated again in the light of minimally invasive esophagectomy. Methods: A comprehensive search was performed in multiple databases to identify randomized controlled trials investigating the topic. Two independent authors performed the selection based on predefined criteria. Statistical analysis was performed to assess any significant difference, then the bias and quality of the data were estimated. Results: Nine relevant RCTs consisting of 529 patients with esophageal cancer were identified. No significance was found in mortality [odds ratio (OR): 0.85; p = 0.642], anastomosis leakage (OR: 0.57; p = 0.254), respiratory morbidity (OR: 0.51; p = 0.214) and vomiting (OR: 0.74; p = 0.520), however the results about gastric emptying time (GET) were controversial (weighted mean difference (WMD): −67.71; p = 0.009, OR: 2.75; p = 0.072). Significant heterogeneity was not detected except for GET. Trial sequential analyses (TSA) show that a certain conclusion would require more data except in the binary variables of GET. Conclusion: We conclude that the pyloric drainage procedure is not routinely necessary, but further well-designed studies would be needed, especially in Europe.
C1 [Csontos, Armand] University of Pecs, Department of SurgeryPecs, Hungary.
[Nemeth, David] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Szako, Lajos] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Berke, Gergo] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Sindler, Lili Dora] University of Pecs, Department of SurgeryPecs, Hungary.
[Berki, David] Military Hospital Medical Centre, Hungarian Defense Forces, First Department of SurgeryBudapest, Hungary.
[Papp, Csenge] University of Pecs, Department of SurgeryPecs, Hungary.
[Hegyi, Peter] University of Pecs, Institute for Translational MedicinePecs, Hungary.
[Vereczkei, Andras] University of Pecs, Department of SurgeryPecs, Hungary.
[Papp, Andras] University of Pecs, Department of SurgeryPecs, Hungary.
RP Csontos, A (reprint author), University of Pecs, Department of Surgery, Pecs, Hungary.
EM csontos.armand@pte.hu
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611823
EP 1611833
DI 10.3389/pore.2024.1611823
PG 11
ER
PT J
AU Liao, CChH
Bakoglu, N
Cesmecioglu, E
Hanna, M
Pareja, F
Wen, H
D’Alfonso, T
Brogi, E
Yagi, Y
Ross, D
AF Liao, Connie Chiu-Hsiang
Bakoglu, Nilay
Cesmecioglu, Emine
Hanna, Matthew
Pareja, Fresia
Wen, Y. Hannah
D’Alfonso, M. Timothy
Brogi, Edi
Yagi, Yukako
Ross, S. Dara
TI Semi-automated analysis of HER2 immunohistochemistry in invasive breast carcinoma using whole slide images: utility for interpretation in clinical practice
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE HER2; immunohistochemistry; breast carcinoma; whole slide imaging; semiautomated analysis
ID HER2; immunohistochemistry; breast carcinoma; whole slide imaging; semiautomated analysis
AB Human epidermal growth factor receptor 2 (HER2) gene amplification and subsequent protein overexpression is a strong prognostic and predictive biomarker in invasive breast carcinoma (IBC). ASCO/CAP recommended tests for HER2 assessment include immunohistochemistry (IHC) and/or in situ hybridization (ISH). Accurate HER2 IHC scoring (0, 1+, 2+, 3+) is key for appropriate classification and treatment of IBC. HER2-targeted therapies, including anti-HER2 monoclonal antibodies and antibody drug conjugates (ADC), have revolutionized the treatment of HER2-positive IBC. Recently, ADC have also been approved for treatment of HER2-low (IHC 1+, IHC 2+/ ISH-) advanced breast carcinoma, making a distinction between IHC 0 and 1+ crucial. In this focused study, 32 IBC with HER2 IHC scores from 0 to 3+ and HER2 FISH results formed a calibration dataset, and 77 IBC with HER2 IHC score 2+ and paired FISH results (27 amplified, 50 nonamplified) formed a validation dataset. H&E and HER2 IHC whole slide images (WSI) were scanned. Regions of interest were manually annotated and IHC scores generated by the software QuantCenter (MembraneQuant application) by 3DHISTECH Ltd. (Budapest, Hungary) and compared to the microscopic IHC score. H-scores [(3×%IHC3+) +(2×%IHC2+) +(1×% IHC1+)] were calculated for semi-automated (MembraneQuant) analysis. Concordance between microscopic IHC scoring and 3DHISTECH MembraneQuant semi-automated scoring in the calibration dataset showed a Kappa value of 0.77 (standard error 0.09). Microscopic IHC and MembraneQuant image analysis for the detection of HER2 amplification yielded a sensitivity of 100% for both and a specificity of 56% and 61%, respectively. In the validation set of IHC 2+ cases, only 13 of 77 cases (17%) had discordant results between microscopic and MembraneQuant images, and various artifacts limiting the interpretation of HER2 IHC, including cytoplasmic/granular staining and crush artifact were noted. Semi-automated analysis using WSI and microscopic evaluation yielded similar HER2 IHC scores, demonstrating the potential utility of this tool for interpretation in clinical practice and subsequent accurate treatment. In this study, it was shown that semi-automatic HER2 IHC interpretation provides an objective approach to a test known to be quite subjective.
C1 [Liao, Connie Chiu-Hsiang] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Bakoglu, Nilay] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Cesmecioglu, Emine] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Hanna, Matthew] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Pareja, Fresia] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Wen, Y. Hannah] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[D’Alfonso, M. Timothy] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Brogi, Edi] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Yagi, Yukako] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Ross, S. Dara] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
RP Ross, D (reprint author), Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory Medicine, New York, USA.
EM rossd@mskcc.org
CR Wolff AC, Somerfield MR, Dowsett M, Hammond ME, Hayes DF, McShane LM, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO–College of American Pathologists Guideline Update. J Clin Oncol, 2023, 41(22):3867–72., DOI 10.1200/JCO.22.02864
Hechtman JF, Ross DS. The past, present, and future of HER2, ERBB2, in cancer: approaches to molecular testing and an evolving role in targeted therapy. Cancer Cytopathology, 2019, 127(7):428–31., DOI 10.1002/cncy.22124
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Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol, 2020, 38(17):1951–62., DOI 10.1200/JCO.19.02488
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Smith B, Hermsen M, Lesser E, Ravichandar D, Kremers W. Developing image analysis pipelines of whole-slide images: pre-and post-processing. J Clin Translational Sci, 2021, 5(1):e38., DOI 10.1017/cts.2020.531
Manuel C, Zehnder P, Kaya S, Sullivan R, Hu F. Impact of color augmentation and tissue type in deep learning for hematoxylin and eosin image super resolution. J Pathol Inform, 2022, 13:100148., DOI 10.1016/j.jpi.2022.100148
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Ohnishi C, Ohnishi T, Ntiamoah P, Ross DS, Yamaguchi M, Yagi Y. Standardizing HER2 immunohistochemistry assessment: calibration of color and intensity variation in whole slide imaging caused by staining and scanning. Appl Microsc, 2023, 53(1):8., DOI 10.1186/s42649-023-00091-8
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Hanna MG, Parwani A, Sirintrapun SJ. Whole slide imaging: technology and applications. Adv Anat Pathol, 2020, 27(4):251–9., DOI 10.1097/PAP. 0000000000000273
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611826
EP 1611835
DI 10.3389/pore.2024.1611826
PG 10
ER
PT J
AU Han, Y
Qiu, W
Zhang, Y
Hua, M
Liu, Sh
Dong, Z
AF Han, Yibing
Qiu, Wen
Zhang, Yu
Hua, Mengmeng
Liu, Shaohua
Dong, Zuoqing
TI From prenatal diagnosis to surgical treatment: two case reports of congenital granular cell epulis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; surgical treatment; congenital granular cell epulis; prenatal diagnosis; oral and maxillofacial regions
ID case report; surgical treatment; congenital granular cell epulis; prenatal diagnosis; oral and maxillofacial regions
AB Herein, we detail a multidisciplinary approach and sequential treatment for two infants with congenital granular cell epulis (CGCE). Ultrasonic examinations at 34 weeks of gestation revealed prominent oral masses in both fetuses. To devise a carefully considered treatment strategy, a comprehensive multidisciplinary consultation including oral and maxillofacial surgeons, pediatricians, obstetricians, and anesthesiologists was convened. Following cesarean sections, the lesions were successfully removed, measuring approximately 30 × 15 mm and 30 × 20 mm in size, respectively. Immunohistochemical analysis showed that vimentin was positive, S-100 protein was negative, and NSE protein and CD68 protein were negative. These findings underscore the importance of prenatal diagnosis of congenital granular cell epulis for the effective management of these rare benign conditions.
C1 [Han, Yibing] Qi Lu Hospital of Shandong University, Department of Oral and Maxillofacial SurgeryJinan, Shandong, China.
[Qiu, Wen] Shandong Academy of Medical SciencesJinan, Shandong, China.
[Zhang, Yu] Shandong University, Qilu Hospital, Department of PathologyJinan, Shandong, China.
[Hua, Mengmeng] Qi Lu Hospital of Shandong University, Department of Oral and Maxillofacial SurgeryJinan, Shandong, China.
[Liu, Shaohua] Qi Lu Hospital of Shandong University, Department of Oral and Maxillofacial SurgeryJinan, Shandong, China.
[Dong, Zuoqing] Qi Lu Hospital of Shandong University, Department of Oral and Maxillofacial SurgeryJinan, Shandong, China.
RP Dong, Z (reprint author), Qi Lu Hospital of Shandong University, Department of Oral and Maxillofacial Surgery, Jinan, China.
EM dongzq@126.com
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NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611834
EP 1611841
DI 10.3389/pore.2024.1611834
PG 8
ER
PT J
AU Casanova, J
da Costa, A
Lopes, PA
Catarino, A
Nave, M
Sousa, CA
Lima, J
AF Casanova, Joao
da Costa, G. Ana
Lopes, Pestana Ana
Catarino, Ana
Nave, Monica
Sousa, Carla Ana
Lima, Jorge
TI Molecular classification of endometrial cancer: preliminary experience from a single Portuguese academic center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE endometrial cancer; molecular subtypes; molecular profiling; POLE mutation; DNA sequencing
ID endometrial cancer; molecular subtypes; molecular profiling; POLE mutation; DNA sequencing
AB Background: Since the seminal publication of the TCGA consortium in 2013, the molecular classification of endometrial cancer has been widely accepted as a new and powerful tool to better understand the natural history of this malignancy. Adoption of routine molecular classification around the world has been limited. We sought to demonstrate our initial experience in incorporating the four molecular subtypes for endometrioid carcinomas. Methods: This was a retrospective analysis at a single center in Portugal. Molecular classification was determined using immunohistochemical staining for MMR and p53 and Sanger Sequencing to determine POLE mutation status as per published PROMISE method. Descriptive statistics were reported. Results: 20 patients with endometrioid histology were included. Median age of the cohort was 64 years (range 45–76). Median Body Mass Index (kg/m2) was 29.81 (range 21.3–43.1). In terms of tumor grading, 16 (80%) of the endometrial carcinomas of the cohort were low-grade (either grade 1 or grade 2). 16 (80%) of the cases were FIGO stage I. Regarding the molecular classification the tumors were classified as: MMRd [n = 6 (30%)]; p53 abn [n = 2 (10%)]; NSMP (n = 10 (50%)), POLE ultramut [n = 2 (10%)]. Conclusion: Despite the small sample size, we were able to show that molecular classification is feasible. To our knowledge this is the first cohort of endometroid endometrial carcinomas fully characterized according to the TCGA classification in Portugal, from one single center.
C1 [Casanova, Joao] Hospital da Luz Lisboa, Department of Surgery, Obstetrics and Gynecology ServiceLisbon, Portugal.
[da Costa, G. Ana] Hospital da Luz Lisboa, Department of Surgery, Obstetrics and Gynecology ServiceLisbon, Portugal.
[Lopes, Pestana Ana] Hospital da Luz Lisboa, Department of Pathology, Gynecologic Oncology UnitLisbon, Portugal.
[Catarino, Ana] Hospital da Luz Lisboa, Department of Pathology, Gynecologic Oncology UnitLisbon, Portugal.
[Nave, Monica] Hospital da Luz Lisboa, Department of Oncology, Gynecologic Oncology UnitLisbon, Portugal.
[Sousa, Carla Ana] GenoMed - Diagnosticos de Medicina MolecularLisbon, Portugal.
[Lima, Jorge] Hospital da Luz Lisboa, Department of Surgery, Obstetrics and Gynecology ServiceLisbon, Portugal.
RP Lima, J (reprint author), Hospital da Luz Lisboa, Department of Surgery, Obstetrics and Gynecology Service, Lisbon, Portugal.
EM jorgeramoslima@sapo.pt
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Vermij L, Leon-Castillo A, Singh N, Powell ME, Edmondson RJ, Genestie C, et al. p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial. Mod Pathol, 2022, 35(10):1475–83. From NLM Medline., DOI 10.1038/s41379-022-01102-x
Kasius JC, Pijnenborg JMA, Lindemann K, Forsse D, van Zwol J, Kristensen GB, et al. Risk stratification of endometrial cancer patients: FIGO stage, biomarkers and molecular classification. Cancers, Basel,, 2021, 13(22):5848. From NLM PubMed-not-MEDLINE., DOI 10.3390/cancers13225848
van den Heerik A, Horeweg N, Nout RA, Lutgens L, van der Steen-Banasik EM, Westerveld GH, et al. PORTEC-4a: international randomized trial of molecular profilebased adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer, 2020, 30(12):2002–7. From NLM., DOI 10.1136/ijgc-2020-001929
Concin N,Matias-Guiu X, Vergote I, Cibula D,Mirza MR,Marnitz S, et al. ESGO/ ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int JGynecol Cancer, 2021, 31(1):12–39. FromNLMMedline., DOI 10.1136/ijgc-2020-002230
Billingsley CC, Cohn DE, Mutch DG, Hade EM, Goodfellow PJ. Prognostic significance of POLE exonuclease domain mutations in high-grade endometrioid endometrial cancer on survival and recurrence: a subanalysis. Int J Gynecol Cancer, 2016, 26(5):933–8. From NLM Medline., DOI 10.1097/IGC.0000000000000681
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Meng B, Hoang LN, McIntyre JB, Duggan MA, Nelson GS, Lee CH, et al. POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium. Gynecol Oncol, 2014, 134(1): 15–9. From NLM Medline., DOI 10.1016/j.ygyno.2014.05.006
Yu S, Sun Z, Zong L, Yan J, Yu M, Chen J, et al. Clinicopathological and molecular characterization of high-grade endometrial carcinoma with POLE mutation: a single center study. J Gynecol Oncol, 2022, 33(3):e38. From NLM Medline., DOI 10.3802/jgo.2022.33.e38
Zong L, Mo S, Sun Z, Lu Z, Chen J, Yu S, et al. Incorporating molecular classification when stratifying the survival risk of patients with high-grade endometrial carcinomas. J Clin Med, 2023, 12(2):530. From NLM PubMed-not- MEDLINE., DOI 10.3390/jcm12020530
Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer, 2017, 123(5):802–13. From NLM Medline., DOI 10. 1002/cncr.30496
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611835
EP 1611842
DI 10.3389/pore.2024.1611835
PG 8
ER
PT J
AU Bicsko, RR
Nyilas, R
Szasz, R
Varoczy, L
Kiss, A
Udvardy, M
Illes,
Gergely, L
AF Bicsko, Rahel Reka
Nyilas, Renata
Szasz, Robert
Varoczy, Laszlo
Kiss, Attila
Udvardy, Miklos
Illes, Arpad
Gergely, Lajos
TI The efficacy and safety of second salvage autologous transplantation in myeloma patients
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; salvage therapy; salvage transplantation; second autologous stem cell transplantation; survival
ID multiple myeloma; salvage therapy; salvage transplantation; second autologous stem cell transplantation; survival
AB Despite the availability of many novel therapies for multiple myeloma, it remains an incurable disease with relapse fated in almost all patients. In the era of modern agents, second autologous stem cell transplantation still holds its role in patients relapsing after first-line autologous transplant. The authors reviewed a single-center experience with a second auto-SCT for relapsed multiple myeloma. Thirty patients had received a salvage auto-SCT at the institution. The median follow-up after diagnosis was 86 months, and the median time between transplants was 59.1 months. Response before second ASCT was the following: CR – 11 cases, VGPR – 9 cases, PR – 10 cases. Most patients received reduced dose (140 mg/m2) of melphalan as a conditioning regimen for the second auto-SCT. Treatment-related mortality was 3%. With a median followup time of 34 months after the second transplant, median progression-free survival was 24 months. The median PFS in the patients achieving CR or VGPR at day 100 after the second transplantation was 32 months. By 15 months, all patients achieved only partial remission progressed, with a median PFS of 8.5 months. During the follow-up period, no MDS or AML developed, and the frequency of second malignancy was also low, 3%. In conclusion, second autologous stem cell transplantation is a well-tolerated and effective treatment option for relapsed multiple myeloma in selected patients, though with a shorter PFS than in first remission.
C1 [Bicsko, Rahel Reka] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Nyilas, Renata] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Szasz, Robert] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Varoczy, Laszlo] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Kiss, Attila] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Udvardy, Miklos] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Illes, Arpad] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
[Gergely, Lajos] University of Debrecen, Faculty of Medicine, Department of HematologyDebrecen, Hungary.
RP Bicsko, RR (reprint author), University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
EM bicskorekaa@gmail.com
CR Barlogie B, Gahrton G. Bone marrow transplantation in multiple myeloma. Bone Marrow Transpl, 1991, 7:71–9.
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Lahuerta JJ, Grande C, Martinez-Lopez J, De La Serna J, Toscano R, Ortiz MC, et al. Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Espanol de Sindromes Linfoproliferativos/Trasplante Autologo de Medula Osea phase II trial. Br J Haematol, 2003, 120:296–303., DOI 10.1046/j.1365-2141.2003.04067.x
Krivanova A, Hajek R, Krejci M, Scudla V, Indrak K, Bacovsky J, et al. Second autologous transplantation for multiple myeloma patients relapsing after the first autograft - a pilot study for the evaluation of experimental maintenance therapies. Report of the prospective non-randomized pilot study of the Czech Myeloma Group. Onkologie, 2004, 27:275–9., DOI 10.1159/000077977
Al Hadidi S, Ababneh O, Schinke C, Thanendrarajan S, Bailey C, Smith RT, et al. Three yearsmaintenance with VRD in multiplemyeloma: results of total therapy IIIB with a 15-year follow up. Blood Adv, 2023, 8:703–7., DOI 10.1182/bloodadvances.2023011601
Qazilbash MH, Saliba R, De Lima M, Hosing C, Couriel D, Aleman A, et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer, 2006, 106:1084–9., DOI 10.1002/cncr.21700
Olin RL, Vogl DT, Porter DL, Luger SM, Schuster SJ, Tsai DE, et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transpl, 2009, 43:417–22., DOI 10.1038/bmt.2008.334
Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S, et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transpl, 2012, 18:773–9., DOI 10.1016/j.bbmt.2011.10.044
Auner HW, Szydlo R, Rone A, Chaidos A, Giles C, Kanfer E, et al. Salvage autologous stem cell transplantation for multiple myeloma relapsing or progressing after up-front autologous transplantation. Leuk Lymphoma, 2013, 54:2200–4., DOI 10.3109/10428194.2013.773998
Grovdal M, Nahi H, Gahrton G, Liwing J, Waage A, Abildgaard N, et al. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT. Bone Marrow Transpl, 2015, 50:808–12., DOI 10.1038/bmt.2015.39
Lemieux C, Muffly LS, Iberri DJ, Craig JK, Johnston LJ, Lowsky R, et al. Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma. Bone Marrow Transpl, 2021, 56:2664–71., DOI 10.1038/ s41409-021-01371-1
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol, 2016, 17:e328–46., DOI 10.1016/S1470-2045(16)30206-6
Cook G, Liakopoulou E, Pearce R, Cavet J, Morgan GJ, Kirkland K, et al. Factors influencing the outcome of a second autologous stem cell transplant, ASCT, in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transpl, 2011, 17:1638–45., DOI 10.1016/j.bbmt.2011.04.005
Hagen PA, Stiff P. The role of salvage second autologous hematopoietic cell transplantation in relapsed multiple myeloma. Biol Blood Marrow Transpl, 2019, 25:e98–e107., DOI 10.1016/j.bbmt.2018.12.002
Dhakal B, D’Souza A, Kleman A, Chhabra S, Mohan M, Hari P. Salvage second transplantation in relapsed multiple myeloma. Leukemia, 2021, 35(4): 1214–7., DOI 10.1038/s41375-020-1005-8
Galligan D, Williamson S,Myers J, Silbermann R,Medvedova E, Nagle S, et al. Second autologous stem cell transplant as salvage in multiple myeloma - the Oregon health and science university experience. Clin Lymphoma Myeloma Leuk, 2022, 22: 105–12., DOI 10.1016/j.clml.2021.08.008
Pasvolsky O, Yeshurun M, Fraser R, Estrada-Merly N, Rozovski U, Shargian- Alon L, et al. Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis. Bone Marrow Transpl, 2022, 57:31–7., DOI 10.1038/s41409-021-01455-y
Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol, 2005, 23:9227–33., DOI 10.1200/JCO.2005. 03.0551
Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: bologna 96 clinical study. J Clin Oncol, 2007, 25:2434–41., DOI 10.1200/JCO.2006.10.2509
Mehta J. One or two autografts for myeloma. Blood, 2008, 111(7):3899–900., DOI 10.1182/blood-2007-12-127704
Ferment B, Lambert J, Caillot D, Lafon I, Karlin L, Lazareth A, et al. French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma, FENIX): a realworld IFM study from the DESCAR-T registry. Br J Haematol, 2024)., DOI 10.1111/ bjh.19505
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611851
EP 1611857
DI 10.3389/pore.2024.1611851
PG 7
ER
PT J
AU Lakatos, L
Illyes, I
Budai, A
Bencze, V
Szijarto, A
Kiss, A
Banky, B
AF Lakatos, Lorand
Illyes, Ildiko
Budai, Andras
Bencze, Viktoria
Szijarto, Attila
Kiss, Andras
Banky, Balazs
TI Feasibility of indocyanine green (ICG) fluorescence in ex vivo pathological dissection of colorectal lymph nodes—a pilot study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE indocyanine green; colorectal cancer; lymph node; ex vivo; colorectal resection
ID indocyanine green; colorectal cancer; lymph node; ex vivo; colorectal resection
AB Accurate lymph node (LN) retrieval during colorectal carcinoma resection is pivotal for precise N-staging and the determination of adjuvant therapy. Current guidelines recommend the examination of at least 12 mesocolic or mesorectal lymph nodes for accurate staging. Traditional histological processing techniques, reliant on visual inspection and palpation, are time-consuming and heavily dependent on the examiner’s expertise and availability. Various methods have been documented to enhance LN retrieval from colorectal specimens, including intra-arterial ex vivo methylene blue injection. Recent studies have explored the utility of indocyanine green (ICG) fluorescence imaging for visualizing pericolic lymph nodes and identifying sentinel lymph nodes in colorectal malignancies. This study included 10 patients who underwent colon resection for malignant tumors. During surgery, intravenous ICGdye and an endoscopic camerawere employed to assess intestinal perfusion. Post-resection, ex vivo intra-arterial administration of ICG dye was performed on the specimens, followed by routine histological processing and an ICG-assisted lymph node dissection. The objective was to evaluatewhether ICG imaging could identify additional lymph nodes compared to routine manual dissection and to assess the clinical relevance of these findings. For each patient, a minimum of 12 lymph nodes (median = 25.5, interquartile range = 12.25, maximum = 33) were examined. ICG imaging facilitated the detection of a median of three additional lymph nodes not identified during routine processing. Metastatic lymph nodes were found in four patients however no additional metastatic nodes were detected with ICG assistance. Our findings suggest that ex vivo intra-arterial administration of indocyanine green dye can augment lymph node dissection, particularly in caseswhere the number of lymph nodes retrieved is below the recommended threshold of 12.
C1 [Lakatos, Lorand] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Illyes, Ildiko] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Budai, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Bencze, Viktoria] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Szijarto, Attila] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Kiss, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Banky, Balazs] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
RP Lakatos, L (reprint author), Semmelweis University, Department of Transplantation and Surgery, Budapest, Hungary.
EM lakatoslorandl@gmail.com
CR Kim J, Huynh R, Abraham I, Kim E, Kumar RR. Number of lymph nodes examined and its impact on colorectal cancer staging. The Am surgeon, 2006, 72(10):902–5., DOI 10.1177/000313480607201013
Markl B, Roessle J, Arnholdt HM, Schaller T, Krammer I, Cacchi C, et al. The clinical significance of lymph node size in colon cancer. Mod Pathol, 2012, 25: 1413–22., DOI 10.1038/modpathol.2012.92
Destri GL, Di Carlo I, Scilletta R, Scilletta B, Puleo S. Colorectal cancer and lymph nodes: the obsession with the number 12. World J Gastroenterol WJG, 2014, 20(8):1951–60., DOI 10.3748/wjg.v20.i8.1951
Borowski DW, Banky B, Banerjee AK, Agarwal AK, Tabaqchali MA, Garg DK, et al. Intra-arterial methylene blue injection into ex vivo colorectal cancer specimens improves lymph node staging accuracy: a randomized controlled trial. Colorectal Dis, 2014, 16(9):681–9. PMID: 24911342., DOI 10.1111/codi.12681
Gregurek SF, Wu HH. Can GEWF solution improve the retrieval of lymph nodes from colorectal cancer resections? Arch Pathol Lab Med, 2009, 133(1):83–6. PMID: 19123742., DOI 10.1043/1543-2165-133.1.83
Schofield JB,Mounter NA, Mallett R, Haboubi NY. The importance of accurate pathological assessment of lymph node involvement in colorectal cancer. Colorectal Dis, 2006, 8(6):460–70., DOI 10.1111/j.1463-1318.2006.01044.x
Chand M, Keller DS, Joshi HM, Devoto L, Rodriguez-Justo M, Cohen R. Feasibility of fluorescence lymph node imaging in colon cancer: FLICC. Tech Coloproctol, 2018, 22(4):271–7. Epub 2018 Mar 17. PMID: 29551004., DOI 10.1007/ s10151-018-1773-6
Sposito C, Maspero M, Belotti P, Simonotti N, Altomare M, Ciana P, et al. Indocyanine green fluorescence-guided surgery for gastrointestinal tumors: a systematic review. Ann Surg Open, 2022, 3(3):e190. PMID: 37601143; PMCID: PMC10431291., DOI 10.1097/AS9.0000000000000190
Watanabe J, OtaM, Suwa Y, Suzuki S, Suwa H,MomiyamaM, et al. Evaluation of the intestinal blood flow near the rectosigmoid junction using the indocyanine green fluorescence method in a colorectal cancer surgery. Int J colorectal Dis, 2015, 30:329–35., DOI 10.1007/s00384-015-2129-6
Markl B, Arnholdt HM, Jahnig H, Spatz H, Anthuber M, Oruzio DV, et al. A new concept for the role of ex vivo sentinel lymph nodes in node-negative colorectal cancer. Ann Surg Oncol, 2010, 17:2647–55., DOI 10.1245/s10434-010-1030-3
Leiloglou M, Kedrzycki MS, Chalau V, Chiarini N, Thiruchelvam PT, Hadjiminas DJ, et al. Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation. Scientific Rep, 2022, 12(1):8607., DOI 10.1038/s41598-022-12504-x
Fry DE. The Hawthorne effect revisited. Dis Colon Rectum, 2018, 61(1):6–7. PMID: 29219914., DOI 10.1097/DCR.0000000000000928
Edler D, Ohrling K, Hallstrom M, Karlberg M, Ragnhammar P. The number of analyzed lymph nodes–a prognostic factor in colorectal cancer. Acta Oncologica, 2007, 46(7):975–81., DOI 10.1080/02841860701203537
Keller DS, Berho M, Perez RO, Wexner SD, Chand M. The multidisciplinary management of rectal cancer. Nat Rev Gastroenterol Hepatol, 2020, 17(7):414–29., DOI 10.1038/s41575-020-0275-y
Brouwer NP, Stijns RC, Lemmens VE, Nagtegaal ID, Beets-Tan RG, Futterer JJ, et al. Clinical lymph node staging in colorectal cancer; a flip of the coin? Eur J Surg Oncol, 2018, 44(8):1241–6., DOI 10.1016/j.ejso.2018.04.008
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Susztak N, Besznyak I, Almasi K, Bursics A, Kelemen D, Borowski DW, et al. Improved accuracy of lymph node staging and long-term survival benefit in colorectal cancer with ex vivo arterial methylene blue infiltration. Pathol Oncol Res, 2022, 28: 1610742. PMID: 36330051; PMCID: PMC9624224., DOI 10.3389/pore.2022.1610742
Tan L, Liu ZL, Ma Z, He Z, Tang LH, Liu YL, et al. Prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: a meta-analysis. World J Gastrointest Oncol, 2020, 12(12):1443–55. PMID: 33362914; PMCID: PMC7739152., DOI 10.4251/wjgo.v12.i12.1443
Lykke J, Jess P, Roikjaer O, Danish Colorectal Cancer Group. Increased lymph node yield is associated with improved survival in rectal cancer irrespective of neoadjuvant treatment: results from a national cohort study. Dis Colon Rectum, 2015, 58:823–30., DOI 10.1097/DCR.0000000000000429
Parnaby CN, Scott NW, Ramsay G, MacKay C, Samuel L, Murray GI, et al. Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection. Br J Cancer, 2015, 113(2):212–9. Epub 2015 Jun 16. PMID: 26079302; PMCID: PMC4506392., DOI 10.1038/bjc.2015.211 Pathology &
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611853
EP 1611859
DI 10.3389/pore.2024.1611853
PG 7
ER
PT J
AU Deme, D
Tamaskovics, FB
Jammoul, N
Kovacs, S
Kayode, OK
Grice, J
Telekes, A
AF Deme, Daniel
Tamaskovics, Ferenc Balint
Jammoul, Nizar
Kovacs, Sandor
Kayode, Oladunjoye Kmmanuel
Grice, W. James
Telekes, Andras
TI Corrigendum: Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Technical Report
DE breast cancer; pathological characteristics; OncotypeDX; recurrence score; observation oriented modeling
ID breast cancer; pathological characteristics; OncotypeDX; recurrence score; observation oriented modeling
AB A Corrigendum on Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center by Deme D, Tamaskovics BF, Jammoul N, Kovacs S, Kayode EO, Grice JWand Telekes A (2024). Pathol. Oncol. Res. 30:1611735. doi: 10.3389/pore.2024.1611735
C1 [Deme, Daniel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Tamaskovics, Ferenc Balint] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Jammoul, Nizar] Szent Lazar Megyei Korhaz, Patologiai OsztalySalgotarjan, Hungary.
[Kovacs, Sandor] University of Debrecen, Department of Economical and Financial MathematicsDebrecen, Hungary.
[Kayode, Oladunjoye Kmmanuel] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
[Grice, W. James] Oklahoma State University, Department of PsychologyStillwater, OK, USA.
[Telekes, Andras] Szent Lazar Megyei Korhaz, Onkologiai OsztalySalgotarjan, Hungary.
RP Deme, D (reprint author), Szent Lazar Megyei Korhaz, Onkologiai Osztaly, Salgotarjan, Hungary.
EM danieldeme_md@ymail.com
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611862
EP 1611865
DI 10.3389/pore.2024.1611862
PG 4
ER
PT J
AU Gascard, P
Wang, X
Nosrati, M
Kim, K
Kashani-Sabet, M
Tlsty, Th
Leong, S
Hendrix, M
AF Gascard, D. Philippe
Wang, Xianhong
Nosrati, Mehdi
Kim, B. Kevin
Kashani-Sabet, Mohammed
Tlsty, D. Thea
Leong, P. Stanley
Hendrix, J. C. Mary
TI Higher Nodal expression is often associated with poorer survival in patients diagnosed with melanoma and treated with anti-PD1 therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE melanoma; nodal; anti-PD1 therapy; immune checkpoint inhibitors; multiplex immunohistochemistry
ID melanoma; nodal; anti-PD1 therapy; immune checkpoint inhibitors; multiplex immunohistochemistry
AB Advanced melanoma is considered the most aggressive and deadly form of skin cancer whose incidence has been rising over the past three decades. In the absence of treatment, the median overall survival for advanced-stage metastatic disease is less than 6 months. Although most melanomas detected at an early stage can be cured with surgery, a subset of these eventually metastasize. Therefore, a critical need exists to identify unique molecular features that would be predictive of long-term outcome and response to specific therapies. Recent promising therapeutic regimens have included the use of immune checkpoint inhibitors, such as anti-PD1 antibodies. However, the ability to identify responders and non-responders to this therapy remains elusive. To address this challenge at the molecular level, previously our laboratory identified the emergence of a stem cell phenotype associated with advanced melanoma and other aggressive forms of cancer. Underlying this phenotype is the aberrant re-expression of the embryonic morphogen “Nodal”. Particularly noteworthy, we have observed Nodal to remain in advanced tumors of non-responders to standard-of-care therapies (i.e., BRAFi). This pilot study is the first proof-of-principle attempt to predict treatment response survival outcome in a small cohort of melanoma patients receiving anti-PD1 immune checkpoint inhibitor therapy – based on their Nodal expression profile. Using advanced multiplex immunohistochemistry-based digital pathology, the major finding of this preliminary study indicates that higher Nodal expression is often associated with poorer overall survival after anti-PD1 therapy, reaching nearly statistical relevance.
C1 [Gascard, D. Philippe] University of California San Francisco, Department of PathologySan Francisco, CA, USA.
[Wang, Xianhong] University of California San Francisco, Department of PathologySan Francisco, CA, USA.
[Nosrati, Mehdi] Sutter Health, Center for Melanoma Research and Treatment, California Pacific Medical CenterSan Francisco, CA, USA.
[Kim, B. Kevin] Sutter Health, Center for Melanoma Research and Treatment, California Pacific Medical CenterSan Francisco, CA, USA.
[Kashani-Sabet, Mohammed] Sutter Health, Center for Melanoma Research and Treatment, California Pacific Medical CenterSan Francisco, CA, USA.
[Tlsty, D. Thea] University of California San Francisco, Department of PathologySan Francisco, CA, USA.
[Leong, P. Stanley] Sutter Health, Center for Melanoma Research and Treatment, California Pacific Medical CenterSan Francisco, CA, USA.
[Hendrix, J. C. Mary] Shepherd University, Department of BiologyShepherdstown, WV, USA.
RP Hendrix, M (reprint author), Shepherd University, Department of Biology, Shepherdstown, USA.
EM mhendrix@shepherd.edu
CR American Cancer Society. Key statistics for melanoma skin cancer, 2023).
Garg M, Couturier DL, Nsengimana J, Fonseca NA, Wongchenko M, Yan Y, et al. Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nat Commun, 2021, 12(1):1137., DOI 10.1038/s41467-021-21207-2
Netanely D, Leibou S, Parikh R, Stern N, Vaknine H, Brenner R, et al. Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns. Oncogene, 2021, 40(10):1792–805., DOI 10.1038/s41388-021-01665-0
Whitman ED, Koshenkov VP, Gastman BR, Lewis D, Hsueh EC, Pak H, et al. Integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. JCO Precis Oncol, 2021, 5:1466–79., DOI 10.1200/PO.21.00162
Karapetyan L, Gooding W, Li A, Yang X, Knight A, Abushukair HM, et al. Sentinel lymph node gene expression signature predicts recurrence-free survival in cutaneous melanoma. Cancers, Basel,, 2022, 14(20):4973., DOI 10.3390/ cancers14204973
Shui IM, Scherrer E, Frederickson A, Li JW, Mynzhassarova A, Druyts E, et al. Resistance to anti-PD1 therapies in patients with advanced melanoma: systematic literature review and application of the Society for Immunotherapy of Cancer Immunotherapy Resistance Taskforce anti-PD1 resistance definitions. Melanoma Res, 2022, 32(6):393–404., DOI 10.1097/CMR.0000000000000850
Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature, 2000, 406(6795):536–40., DOI 10.1038/35020115
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Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Long-term outcomes with nivolumab Plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol, 2022, 40(2): 127–37., DOI 10.1200/JCO.21.02229
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611889
EP 1611896
DI 10.3389/pore.2024.1611889
PG 8
ER
PT J
AU Nagy, FZs
Arvai, K
Lakatos, P
Beke Debreceni, I
Szili, B
Istenes, I
Bodor, Cs
Demeter, J
AF Nagy, Flora Zsofia
Arvai, Kristof
Lakatos, Peter
Beke Debreceni, Ildiko
Szili, Balazs
Istenes, Ildiko
Bodor, Csaba
Demeter, Judit
TI Case report: Comprehensive clinical, pathological and genetic investigations to decipher the background of cyclic thrombocytopenia
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE case report; WES; cyclic thrombocytopaenia; thrombocytopaenia; cyclic
ID case report; WES; cyclic thrombocytopaenia; thrombocytopaenia; cyclic
AB Cyclic thrombocytopenia (CTP) is a rare disease characterized by the oscillations seen in the platelet count of the patients. The pathomechanism of the disease is poorly understood, several pathological processes have been implied in the background of CTP. In our current study, we aimed to thoroughly investigate the case of a 41-year-old female patient with a 22-year history of CTP. Wide-ranging laboratory testing, histological analyses and genetic investigations were carried out to investigate all the defects and alterations of physiological pathways described in the background of CTP to date. Bone marrow biopsy showed normal hemopoiesis with the abundance of megakaryocytes, some of which displayed hypolobulated nuclei. T-cell receptor rearrangement studies showed a polyclonal pattern with no indication of a monoclonal cell population. Flow cytometric assessment of the platelets revealed large number of immature platelets and decreased expression of glycoprotein IIb and IIIa at platelet zenith. Increased expression of glycoprotein IIb, IIIa and glycoprotein Ib-IX complex was observed at the nadir of the cycle. Whole exome sequencing revealed a heterozygous missense variant of uncertain significance in the SERPINC1 gene, which has been associated with hereditary antithrombin deficiency. The screening of autoantibodies did not reveal signs of autoreactive processes, and no thyroid dysfunction was found. Furthermore, synchronization with the menstrual cycle could not be concluded based on our patient’s case. With our results we contribute to the very limited data known about the long-term course of the disease and provide valuable insights into the genetic architecture of CTP.
C1 [Nagy, Flora Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Arvai, Kristof] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Lakatos, Peter] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Beke Debreceni, Ildiko] University of Debrecen, Faculty of Medicine, Department of Laboratory MedicineDebrecen, Hungary.
[Szili, Balazs] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Istenes, Ildiko] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Bodor, Csaba] Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research GroupBudapest, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Nagy, FZs (reprint author), Semmelweis University, Department of Internal Medicine and Oncology, Budapest, Hungary.
EM nagy.zsofia.flora@semmelweis.hu
CR Oyenuga M, Onyechi A, Sartaj S, Patel R, Sinha J. Cyclic thrombocytopenia: a rare cause of recurrent thrombocytopenia case presentation. Cureus, 2022, 14:10–2., DOI 10.7759/cureus.22525
Arnold DM, Nazy I, Clare R, Jaffer AM, Aubie B, Li N, et al. Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: lessons from the McMaster ITP Registry. Blood Adv, 2017, 1:2414–20., DOI 10.1182/bloodadvances. 2017010942
Kyrle PA, Eichinger S. How I manage cyclic thrombocytopenia. Blood, 2021, 137:178–84., DOI 10.1182/blood.2020008218
Helleberg C, Taaning E, Hansen PB. Cyclic thrombocytopenia successfully treated with low dose hormonal contraception. Am J Hematol, 1995, 48:62–3., DOI 10.1002/ajh.2830480117
Dan K, Inokuchi K, An E, Nomura T. Cell-mediated cyclic thrombocytopenia treated with azathioprine. Br J Haematol, 1991, 77:365–70., DOI 10.1111/j.1365- 2141.1991.tb08585.x
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv, 2019, 3:3829–66., DOI 10.1182/bloodadvances.2019000966
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular Pathology. Genet Med, 2015, 17:405–24., DOI 10.1038/gim.2015.30
Steinbrecher O, Mitrovic M, Eischer L, Sinkovec H, Eichinger S, Kyrle PA. Clinical and laboratory characteristics of cyclic thrombocytopenia: an observational study. Haematologica, 2020, 105:198–201., DOI 10.3324/haematol.2019.237909
Chen G, Chen L, Qin X, Xie X, Li G, Xu B. Cyclic thrombocytopenia related to menstrual cycle: a case report and literature review. Int J Clin Exp Med, 2014, 7: 3595–8.
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Fogarty PF, Stetler-Stevenson M, Pereira A, Dunbar CE. Large granular lymphocytic proliferation-associated cyclic thrombocytopenia. Am J Hematol, 2005, 79:334–6., DOI 10.1002/ajh.20375
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Kojima K, Fujii N, Omoto E, Nose S, Yoneyama M, Sugii Y, et al. Cyclic thrombocytopenia and polycythemia vera. Ann Hematol, 2003, 82:61–3., DOI 10. 1007/s00277-002-0580-2
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Lu Q, Hu Y, Sun J, Cheng Y, Cheung KH, Zhao H. A statistical framework to predict functional non-coding regions in the human genome through integrated analysis of annotation data. Sci Rep, 2015, 5:10576–13., DOI 10.1038/srep10576
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Szabo R, Netzel-Arnett S, Hobson JP, Antalis TM, Bugge TH. Malriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem J, 2005, 390:231–42., DOI 10.1042/ BJ20050299
NR 3
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JUL
PY 2024
VL 30
IS 3
BP 1611914
EP 1611921
DI 10.3389/pore.2024.1611914
PG 8
ER
PT J
AU Zhao, H
Kou, Ch
Zhao, H
Liu, Q
He, M
Wang, C
Zhu, S
Ma, L
Wang, Y
AF Zhao, Han
Kou, Changhua
Zhao, Hao
Liu, Qing
He, Maosheng
Wang, Cong
Zhu, Saisai
Ma, Li
Wang, Yun
TI Impact of limb ischemic preconditioning on the incidence of vein thrombosis in patients with peripherally inserted central catheter
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor; limb ischemic preconditioning; peripherally inserted central catheter; vein thrombosis; PICC-related complications
ID tumor; limb ischemic preconditioning; peripherally inserted central catheter; vein thrombosis; PICC-related complications
AB Background: Peripherally inserted central catheters (PICC) are increasingly used in clinical practice, which also leads to an increased incidence of PICC-related thrombosis. Local thrombus formation could be prevented by limb ischemic preconditioning (IPC). This study aimed to determine whether IPC can prevent deep vein thrombosis in patients with PICC. Methods: A total of 600 breast cancer patients receiving PICC were randomized into two groups between July 2016 and July 2018 at the Department of Radiation Oncology. In the preconditioning group, 5 min of ischemic preconditioning was performed three times before PICC, whereas no preconditioning was performed in the sham group. The coagulation function levels, the PICC-related complications, the length of hospital stay, the cost of hospitalization, and the satisfaction of patients were compared. Results: The coagulation function levels of patients in the preconditioning group were more normal than in patients from the sham group. In total, 56/ 300 patients in the sham group had presence of PICC-related thrombosis, with only 23/300 in the IPC group, with no significant difference in other complications between the two groups. However, a longer hospital stay was observed in the sham group compared to the IPC group. Moreover, the cost of hospitalization was also reduced in the IPC group, which also improved the satisfaction of patients. Conclusion: Limb ischemic preconditioning may attenuate the severity of vein thrombosis in patients with PICC, which contributes to reducing the incidence of PICC-related thrombosis in clinical practice.
C1 [Zhao, Han] Hannover Medical School, Clinic for Kidney and Hypertensive DiseasesHannover, Germany.
[Kou, Changhua] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Hepatobiliary Pancreatic CenterXuzhou, Jiangsu, China.
[Zhao, Hao] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, Department of Vascular SurgeryXuzhou, Jiangsu, China.
[Liu, Qing] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Gynecology DepartmentXuzhou, Jiangsu, China.
[He, Maosheng] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Color Ultrasound DepartmentXuzhou, Jiangsu, China.
[Wang, Cong] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Hepatobiliary Pancreatic CenterXuzhou, Jiangsu, China.
[Zhu, Saisai] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Hepatobiliary Pancreatic CenterXuzhou, Jiangsu, China.
[Ma, Li] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, Department of Thyroid and Breast SurgeryXuzhou, Jiangsu, China.
[Wang, Yun] The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Hepatobiliary Pancreatic CenterXuzhou, Jiangsu, China.
RP Wang, Y (reprint author), The Affiliated Hospital of the Southeast University Medical School, Xuzhou City Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Department of Hepatobiliary Pancreatic Center, Xuzhou, China.
EM wyhh666@gmail.com
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Wu J, Yu C, Zeng X, Sun C. The hepatoprotective effect from ischemiareperfusion injury of remote ischemic preconditioning in the liver related surgery: a meta-analysis. ANZ J Surg, 2022, 92(6):1332–7. Epub 2021 Dec 2. PMID: 34854193., DOI 10.1111/ans.17236
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Yuen HLA, Tran H, Chunilal S. Upper extremity deep vein thrombosis: current knowledge and future directions. Semin Thromb Hemost, 2021, 47(6): 677–91. Epub 2021 May 10. PMID: 33971684., DOI 10.1055/s-0041-1725116
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611596
EP 1611604
DI 10.3389/pore.2024.1611596
PG 9
ER
PT J
AU Bakoglu, N
Sakamoto, H
Yoshida, M
Ohnishi, T
Lee, SY
Smith, L
Yagi, Y
AF Bakoglu, Nilay
Sakamoto, Hirotsugu
Yoshida, Masao
Ohnishi, Takashi
Lee, Seung-Yi
Smith, Lindsey
Yagi, Yukako
TI Artificial intelligence-based automated determination in breast and colon cancer and distinction between atypical and typical mitosis using a cloud-based platform
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE mitosis; colon adenecarcinoma; breast; artificial intelligence; invasive carcinoma
ID mitosis; colon adenecarcinoma; breast; artificial intelligence; invasive carcinoma
AB Artificial intelligence (AI) technology in pathology has been utilized in many areas and requires supervised machine learning. Notably, the annotations that define the ground truth for the identification of different confusing process pathologies, vary from study to study. In this study, we present our findings in the detection of invasive breast cancer for the IHC/ISH assessment system, along with the automated analysis of each tissue layer, cancer type, etc. in colorectal specimens. Additionally, models for the detection of atypical and typical mitosis in several organs were developed using existing whole-slide image (WSI) sets from other AI projects. All H&E slides were scanned by different scanners with a resolution of 0.12–0.50 μm/pixel, and then uploaded to a cloud-based AI platform. Convolutional neural networks (CNN) training sets consisted of invasive carcinoma, atypical and typical mitosis, and colonic tissue elements (mucosa-epithelium, lamina propria, muscularis mucosa, submucosa, muscularis propria, subserosa, vessels, and lymph nodes). In total, 59 WSIs from 59 breast cases, 217 WSIs from 54 colon cases, and 28 WSIs from 23 different types of tumor cases with relatively higher amounts of mitosis were annotated for the training. The harmonic average of precision and sensitivity was scored as F1 by AI. The final AI models of the Breast Project showed an F1 score of 94.49% for Invasive carcinoma. The mitosis project showed F1 scores of 80.18%, 97.40%, and 97.68% for mitosis, atypical, and typical mitosis layers, respectively. Overall F1 scores for the current results of the colon project were 90.02% for invasive carcinoma, 94.81% for the submucosa layer, and 98.02% for vessels and lymph nodes. After the training and optimization of the AI models and validation of each model, external validators evaluated the results of the AI models via blind-reader tasks. The AI models developed in this study were able to identify tumor foci, distinguish in situ areas, define colonic layers, detect vessels and lymph nodes, and catch the difference between atypical and typical mitosis. All results were exported for integration into our in-house applications for breast cancer and AI model development for both wholeblock and whole-slide image-based 3D imaging assessment.
C1 [Bakoglu, Nilay] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Sakamoto, Hirotsugu] Jichi Medical University, Department of Medicine, Division of GastroenterologyTochigi, Japan.
[Yoshida, Masao] Shizuoka Cancer Center, Division of EndoscopyShizuoka, Japan.
[Ohnishi, Takashi] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
[Lee, Seung-Yi] Aiforia TechnologiesCambridge, MA, USA.
[Smith, Lindsey] Flywheel.ioMinneapolis, MN, USA.
[Yagi, Yukako] Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory MedicineNew York, NY, USA.
RP Yagi, Y (reprint author), Memorial Sloan Kettering Cancer Center, Department of Pathology and Laboratory Medicine, New York, USA.
EM yagiy@mskcc.org
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611815
EP 1611829
DI 10.3389/pore.2024.1611815
PG 15
ER
PT J
AU Li, Y
Wang, Y
He, W
AF Li, Yanxi
Wang, Yujiao
He, Weimin
TI Case report: Orbital myeloid sarcoma: a report of two rare cases and review of the literature
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE myeloid sarcoma (MS); orbit; histopathology; immunohistochemistry; diagnosis; treatment
ID myeloid sarcoma (MS); orbit; histopathology; immunohistochemistry; diagnosis; treatment
AB Myeloid sarcoma (MS) occurs when primitive or naive myeloid cells form outside the bone marrow. It occurs mainly in soft/connective tissue and skin; orbital involvement is rare. We report the cases of two female adults, analyze the clinicopathologic characteristics, and review the literature. The average age of both patients was 28 years and they presented unilateral proptosis combined with varying degrees of impaired visual acuity and restricted ocular motility in the affected eye. Despite this, they maintained good overall health and no notable family history. However, the patients had no systemic clinical manifestations of acute myeloid leukemia (AML). Both patients underwent surgical resection of the orbital tumor. Immunohistochemistry showed positive staining for CD43, Leukocyte Common Antigen (LCA), and myeloperoxidase (MPO) and a high level of positive staining for Ki67, which were diagnostic for MS. Bone marrow cytology examination showed no apparent abnormalities. Postoperative chemotherapy, local radiotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were performed in Case 1, while the second patient underwent adjuvant chemotherapy and radiotherapy. No recurrence or metastasis was found in either patient during follow-up (one more than 5 years, the other more than 10 years). The occurrence of orbital MS is infrequent, with atypical clinical and imaging findings. The diagnosis depends on pathomorphology and immunohistochemical staining, and the prognosis is good with postoperative adjuvant chemotherapy, local radiotherapy, and allo- HSCT.
C1 [Li, Yanxi] West China Hospital of Sichuan University, Department of OphthalmologyChengdu, Sichuan, China.
[Wang, Yujiao] West China Hospital of Sichuan University, Department of OphthalmologyChengdu, Sichuan, China.
[He, Weimin] West China Hospital of Sichuan University, Department of OphthalmologyChengdu, Sichuan, China.
RP He, W (reprint author), West China Hospital of Sichuan University, Department of Ophthalmology, Chengdu, China.
EM hewm888@hotmail.com
CR Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World health organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia, 2022, 36(7): 1703–19., DOI 10.1038/s41375-022-01613-1
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611818
EP 1611824
DI 10.3389/pore.2024.1611818
PG 7
ER
PT J
AU Chen, P
Chen, M
Bu, Y
Che, G
Cheng, Ch
Wang, Y
AF Chen, Pingrun
Chen, Maojia
Bu, Yijie
Che, Guowei
Cheng, Chao
Wang, Yan
TI Prognostic role of lymph node regression in patients with esophageal cancer undergoing neoadjuvant therapy
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Review
DE lymph node regression; esophageal cancer; neoadjuvant therapy; survival; meta-analysis
ID lymph node regression; esophageal cancer; neoadjuvant therapy; survival; meta-analysis
AB Purpose: To clarify the prognostic value of lymph node regression (LNR) status including the lymph node regression grade (LNRG) and N downstaging in patients with esophageal cancer receiving neoadjuvant therapy based on available evidence. Methods: Several databases were searched up to 25 March 2024. The main outcomes included overall survival (OS), disease-free survival (DFS) and cancerspecific survival (CSS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. Subgroup analyses based on the neoadjuvant therapy and pathological type were also conducted. Results: In total, 14 retrospective studies with 3,212 participants were included. Nine and five studies explored the relationship between LNRG and N downstaging and survival, respectively. Pooled results indicated that complete LNR predicted significantly improved OS (HR = 0.47, 95% CI: 0.41–0.55, P < 0.001) and DFS (HR = 0.42, 95% CI: 0.32–0.55, P < 0.001) and subgroup analysis based on neoadjuvant therapy and pathological type manifested similar results. Besides, N downstaging was also significantly related to improved OS (HR = 0.40, 95% CI: 0.21–0.77, P = 0.006) and CSS (HR = 0.27, 95% CI: 0.12–0.60, P < 0.001). Conclusion: LNR could serve as a novel and reliable prognostic factor in patients with esophageal cancer receiving neoadjuvant therapy and complete LNR and N downstaging predict better survival.
C1 [Chen, Pingrun] Sichuan University, West China Hospital, Department of GastroenterologyChengdu, China.
[Chen, Maojia] Sichuan University, West China Hospital, Animal Experiment CenterChengdu, China.
[Bu, Yijie] Sichuan University, West China Hospital, Department of Thoracic SurgeryChengdu, China.
[Che, Guowei] Sichuan University, West China Hospital, Division of Thoracic OncologyChengdu, China.
[Cheng, Chao] Sichuan University, West China Hospital, Department of Thoracic SurgeryChengdu, China.
[Wang, Yan] Sichuan University, West China Hospital, Department of Thoracic SurgeryChengdu, China.
RP Wang, Y (reprint author), Sichuan University, West China Hospital, Department of Thoracic Surgery, Chengdu, China.
EM wangyanxw@wchscu.cn
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611844
EP 1611854
DI 10.3389/pore.2024.1611844
PG 11
ER
PT J
TI Diagnostic challenges in complicated case of glioblastoma
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE diagnostics; cytogenomics; MLPA; I-FISH; aCGH/SNP; gene panel; WGS
ID diagnostics; cytogenomics; MLPA; I-FISH; aCGH/SNP; gene panel; WGS
AB Glioblastoma is the commonest primary malignant brain tumor, with a very poor prognosis and short overall survival. It is characterized by its high intra- and intertumoral heterogeneity, in terms of both the level of single-nucleotide variants, copy number alterations, and aneuploidy. Therefore, routine diagnosis can be challenging in some cases. We present a complicated case of glioblastoma, which was characterized with five cytogenomic methods: interphase fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, comparative genomic hybridization array and singlenucleotide polymorphism, targeted gene panel, and whole-genome sequencing. These cytogenomic methods revealed classical findings associated with glioblastoma, such as a lack of IDH and TERT mutations, gain of chromosome 7, and loss of chromosome 10. At least three pathological clones were identified, including one with whole-genome duplication, and one with loss of 1p and suspected loss of 19q. Deletion and mutation of the TP53 gene were detected with numerous breakends on 17p and 20q. Based on these findings, we recommend a combined approach to the diagnosis of glioblastoma involving the detection of copy number alterations, mutations, and aneuploidy. The choice of the best combination of methods is based on cost, time required, staff expertise, and laboratory equipment. This integrated strategy could contribute directly to tangible improvements in the diagnosis, prognosis, and prediction of the therapeutic responses of patients with brain tumors.
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611875
EP 1611884
DI 10.3389/pore.2024.1611875
PG 10
ER
PT J
AU Gyimesi, Gy
Keczer, B
Rein, P
Horvath, M
Szucs,
Marjai, T
Szijarto, A
Hritz, I
AF Gyimesi, Gyorgy
Keczer, Bank
Rein, Peter
Horvath, Miklos
Szucs, Akos
Marjai, Tamas
Szijarto, Attila
Hritz, Istvan
TI Diagnostic performance of intracystic carcinoembryonic antigen (CEA) versus glucose in differentiation of mucinous and non-mucinous pancreatic cysts
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE pancreatic cyst; endosonography; FNA; intracystic CEA; intracystic glucose
ID pancreatic cyst; endosonography; FNA; intracystic CEA; intracystic glucose
AB Background and Objectives: Pancreatic cysts have various potential for malignant transformation. Differentiating mucinous from non-mucinous cysts is crucial to make the right decision about further management, since mucinous cysts carry the risk of malignancy. Using endoscopic ultrasound (EUS) guided fine needle aspiration to determine intracystic carcinoembryonic antigen (CEA) levels is the recommended method for identifying mucinous cysts, although intracystic glucose assessment has also proved to be an effective tool. This study aims to compare the diagnostic performance of intracystic glucose and CEA in distinguishing between mucinous and nonmucinous pancreatic cystic lesions. Methods: In this single center study, we prospectively collected and analyzed the data of 91 consecutive patients who underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with cytological analysis and measurement of intracystic CEA and glucose levels. The cyst type was classified based on radiological and EUS morphology, string sign, CEA, cytological and histological findings in resected cases. The diagnosis was established retrospectively by three experienced gastroenterologists blinded for glucose level in cases without definitive cytology or histology. We calculated the sensitivity, specificity, the positive- and negative predictive value of glucose and CEA respectively, and compared the two methods. Results: The sensitivity of intracystic glucose versus CEA proved to be 96.2% vs. 69.2% in identifying mucinous cysts, while the specificity of glucose was shown to be 79.5%, compared to 100% for CEA. Conclusion: Intracystic glucose is a sensitive, easily accessible biomarker in identifying mucinous pancreatic cysts, however, the specificity is lower compared to CEA. The measurement of intracystic glucose level could help in decision-making in daily clinical practice, however the diagnostic performance of the method remains inferior to “through-the-needle” techniques, such as confocal laser endomicroscopy and Moray forceps biopsy.
C1 [Gyimesi, Gyorgy] Semmelweis University, School of PhD StudiesBudapest, Hungary.
[Keczer, Bank] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Rein, Peter] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Horvath, Miklos] Semmelweis University, Department of Surgery, Transplantation and Gastroenterology, Division of Interventional GastroenterologyBudapest, Hungary.
[Szucs, Akos] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Marjai, Tamas] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Szijarto, Attila] Semmelweis University, Department of Transplantation and SurgeryBudapest, Hungary.
[Hritz, Istvan] Semmelweis University, Department of Surgery, Transplantation and Gastroenterology, Division of Interventional GastroenterologyBudapest, Hungary.
RP Gyimesi, Gy (reprint author), Semmelweis University, School of PhD Studies, Budapest, Hungary.
EM drgyimesigy@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611881
EP 1611887
DI 10.3389/pore.2024.1611881
PG 7
ER
PT J
AU Czeti,
Sashalmi, S
Takacs, F
Szaloki, G
Kriston, Cs
Varga, G
Farkas, P
Hamed, A
Mark,
Barna, G
AF Czeti, Agnes
Sashalmi, Soma
Takacs, Ferenc
Szaloki, Gabor
Kriston, Csilla
Varga, Gergely
Farkas, Peter
Hamed, Aryan
Mark, Agnes
Barna, Gabor
TI Investigating the effect of immunomagnetic separation on the immunophenotype and viability of plasma cells in plasma cell disorders
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE multiple myeloma; flow cytometry; immunomagnetic separation; immunophenotype; positive selection
ID multiple myeloma; flow cytometry; immunomagnetic separation; immunophenotype; positive selection
AB Plasma cell enrichment plays a pivotal role in the accurate prognosis and molecular characterization of multiple myeloma. The separation is commonly carried out by positive cell selection using CD138 monoclonal antibody conjugated to magnetic beads. Optimally, during the separation procedure, the cells should neither be damaged, nor should their phenotype be significantly altered, as these changes would falsify the results if the isolated cells were subsequently used. For this reason, we investigated the expression patterns of different surface markers by flow cytometry before and after magnetic isolation using bone marrow or peripheral blood samples from 12 patients with plasma cell disorders. The selected markers are not only used as backbone markers in routine diagnostics (CD19, CD38, CD45, CD117, and CD138), but they also play an important role in cell adhesion and connection with microenvironment (CD44, CD49d, CD56, and CD81) or possibly drug resistance (CD69, CD86, and CD184), making them promising targets for myeloma research. Moreover, we examined the effects of separation on cell viability in 8 cases. The intensities of 8 out of the 12 investigated markers were slightly influenced, while CD138, CD38, CD56, and CD184 were changed significantly, however the immunophenotype of the cells was not changed. Positive markers remained positive and negative ones remained negative after the separation procedure. In addition, the number of apoptotic plasma cells was significantly reduced during separation, facilitating further examination of the cells. Our results showed that magnetic isolation can be considered as a reliable option but the immunophenotype of plasma cells should be validated after the separation if the intensities of the markers are important for further experiments.
C1 [Czeti, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sashalmi, Soma] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Takacs, Ferenc] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Szaloki, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Kriston, Csilla] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Varga, Gergely] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Farkas, Peter] Semmelweis University, Department of Internal Medicine and HaematologyBudapest, Hungary.
[Hamed, Aryan] Petz Aladar County Hospital, II. Department of Internal Medicine and HematologyGyor, Hungary.
[Mark, Agnes] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Barna, Gabor] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Barna, G (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM barna.gabor@semmelweis.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611882
EP 1611891
DI 10.3389/pore.2024.1611882
PG 10
ER
PT J
AU Molnar, E
Baranyi, M
Szigeti, K
Hegedus, L
Bordas, F
Gabriel, Zs
Petenyi, G
Tovari, J
Hegedus, B
Timar, J
AF Molnar, Eszter
Baranyi, Marcell
Szigeti, Krisztina
Hegedus, Luca
Bordas, Fanni
Gabriel, Zsofia
Petenyi, Greta
Tovari, Jozsef
Hegedus, Balazs
Timar, Jozsef
TI Combination of farnesyl-transferase inhibition with KRAS G12D targeting breaks down therapeutic resistance in pancreatic cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE PDAC; G12D mutant KRAS; KRAS inhibitor resistance; FTI; combination therapy
ID PDAC; G12D mutant KRAS; KRAS inhibitor resistance; FTI; combination therapy
AB Pancreatic adenocarcinoma is one of the deadliest forms of cancer with no effective therapeutic options. A KRAS mutation can be found in up to 90% of all pancreatic tumors, making it a promising therapeutic target. The introduction of new KRAS inhibitors has been a milestone in the history of KRAS mutant tumors; however, therapeutic resistance limits their efficacy. Thus, new therapeutic options, including combination therapies, are urgently needed. Recently, we have shown that KRAS G12C inhibitors in combination with farnesyl-transferase inhibitors exert synergistic antitumor effects. Here, we provide evidence for the feasibility of this combinational approach to break down resistance in KRAS G12D mutant pancreatic cancer. Although we have shown that the 3D environment dramatically sensitizes cells to MRTX1133 treatment, the synergistic effect of this drug combination is present in both 2D and 3D in the PANC1 pancreatic adenocarcinoma model, which showed high resistance to MRTX1133 in 2D. The effects of the combination treatment show an association with the inhibition of farnesylated regulatory proteins, including HRAS and RHEB, along with the expression level of KRAS. Our study warrants further investigation for the potential applicability of KRAS G12D inhibitors in combination with farnesyl-transferase inhibitors for the treatment of KRAS mutant pancreatic adenocarcinoma.
C1 [Molnar, Eszter] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Baranyi, Marcell] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Szigeti, Krisztina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Hegedus, Luca] University Duisburg-Essen, Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Bordas, Fanni] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Gabriel, Zsofia] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Petenyi, Greta] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tovari, Jozsef] Orszagos Onkologiai Intezet, Nemzeti Tumorbiologiai LaboratoriumBudapest, Hungary.
[Hegedus, Balazs] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Baranyi, M (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM baranyi2marci@gmail.com
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611948
EP 1611959
DI 10.3389/pore.2024.1611948
PG 12
ER
PT J
AU Katib, Y
Essatari, M
AF Katib, Yousef
Essatari, Murad
TI Case report: A rare case of oral sebaceous carcinoma in the upper lip
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE sebaceous carcinoma; oral cavity; lip; immunohistochemistry; treatment; oral cavity
ID sebaceous carcinoma; oral cavity; lip; immunohistochemistry; treatment; oral cavity
AB Sebaceous carcinoma (SC) is a rare aggressive malignant tumor that originates in the adnexal epithelium of the sebaceous gland. While occurrences on the lips are extremely uncommon, there have been a few reported cases in the literature. Our case involves a 47-year-old smoker male who presented with a painless, non-mobile lesion on his upper lip that had been present for 12 months. Upon clinical examination, an ulcerated, exophytic, and irregularly shaped mass was observed on the upper lip. No other intraoral lesions were found. An incisional biopsy was performed, revealing a malignant tumor with a nodular pattern consisting of basaloid cells with obvious sebaceous differentiations and frequent mitoses. The neoplastic cells tested positive for broad-spectrum cytokeratin (AE1-AE3), epithelial membrane antigen (EMA), and P53, while testing negative for S-100 and carcinoembryonic antigen (CEA). Based on these results, a diagnosis of SC of the upper lip was made. This case report and review aimed to describe the histogenesis, unique clinicopathological features, and current treatment options for SC.
C1 [Katib, Yousef] Taibah University, College of MedicineMadinah, Saudi Arabia.
[Essatari, Murad] Prince Noorah Oncology Center, King Abdulaziz Medical CityJeddah, Saudi Arabia.
RP Katib, Y (reprint author), Taibah University, College of Medicine, Madinah, Saudi Arabia.
EM ykatib@taibahu.edu.sa
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611968
EP 1611972
DI 10.3389/pore.2024.1611968
PG 5
ER
PT J
AU Kramer, Zs
Budai, A
Pesti, A
Kulka, J
Tokes, AM
AF Kramer, Zsofia
Budai, Andras
Pesti, Adrian
Kulka, Janina
Tokes, Anna-Maria
TI Invasive micropapillary carcinoma of the breast and invasive breast carcinoma of no special type: a comparison of claudin proteins’ expression and its impact on survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE invasive micropapillary carcinoma of the breast; invasive breast carcinoma of no special type; claudin expression; tight junction; prognosis
ID invasive micropapillary carcinoma of the breast; invasive breast carcinoma of no special type; claudin expression; tight junction; prognosis
AB Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico–basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged. By using immunohistochemistry, we have analysed claudin-1, -3, -4, and -7 tight junction proteins expression and their prognostic value on IMPCs and compared them to invasive breast carcinomas of no special type (IBC-NST) tumors. Our cohort consisted of 37 IMPCs, 36 IBC-NST and 9 mixed IMPC/IBC-NST tumors. Two scoring systems were used to quantify protein expression: a 4-tier scoring system and the H-score method. Distant metastasis free survival (DMFS) intervals and overal survival (OS) data were used for prognosis evaluation. The analysed samples were characterized mainly by low or no claudin-1 expression whereas claudins-3, -4 and -7 showed variable positivity. We have found no significant differences in claudin-3 and -4 protein expression between IMPC and IBC-NST groups with either scoring methods, however high claudin-7 expression was found in significantly more IMPCs than IBC-NST tumors according to the H-score system (p = 0.02). The 4-tier scoring method revealed association of claudin-7 expression with molecular tumor subtypes (p = 0.001). IMPC and IBC-NST tumors did not show difference in DMFS (p = 0.70). In the analysis of pure IMPC and IBC-NST tumors, positive/high claudin-4 protein expression was significantly associated with shorter DMFS (p = 0.02/p = 0.008, respectively according to the two scoring methods). Claudin-3 and claudin-7 expression showed no association with DMFS or OS. Changes in epithelial polarity seem not to be related to claudin-1, -3, and -4 expression. Increased claudin-4 expression may have a role in breast cancer progression.
C1 [Kramer, Zsofia] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Budai, Andras] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Pesti, Adrian] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Kulka, Janina] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Tokes, Anna-Maria] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
RP Kramer, Zs (reprint author), Semmelweis University, 2nd Department of Pathology, Budapest, Hungary.
EM kramer.zsofia@semmelweis.hu
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NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1611987
EP 1611998
DI 10.3389/pore.2024.1611987
PG 12
ER
PT J
AU Pathology and Oncology Research, EO
AF Pathology and Oncology Research, Editorial Office
TI Retraction: The Plasmodium circumsporozoite protein, a novel NF-κB inhibitor, suppresses the growth of SW480
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB A Retraction of the Original Research Article The Plasmodium circumsporozoite protein, a novel NF-κB inhibitor, suppresses the growth of SW480 by Ding Y, Huang X, Liu T, Fu Y, Tan Z, Zheng H, Zhou T, Dai J and Xu W (2012). Pathol. Oncol. Res. 19:11–18. doi: 10.1007/s12253-012-9519-7
C1 [Pathology and Oncology Research, Editorial Office] Frontiers Media SA, Switzerland.
RP Pathology and Oncology Research, EO (reprint author), Frontiers Media SA, , Switzerland.
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1612018
EP 1612019
DI 10.3389/pore.2024.1612018
PG 2
ER
PT J
AU Editorial Office, PaOR
AF Editorial Office, Pathology and Oncology Research
TI Retraction: Effects of gallotannin-enriched extract of Galla Rhois on the activation of apoptosis, cell cycle arrest, and inhibition of migration ability in LLC1 cells and LLC1 tumors
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Retraction
AB A Retraction of the Original Research Article Effects of gallotannin-enriched extract of Galla Rhois on the activation of apoptosis, cell cycle arrest, and inhibition of migration ability in LLC1 cells and LLC1 tumors
C1 [Editorial Office, Pathology and Oncology Research] Frontiers Media SALausanne, Switzerland.
RP Editorial Office, PaOR (reprint author), Frontiers Media SA, Lausanne, Switzerland.
EM editorialoffice@por-journal.com
NR 4
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD OCT
PY 2024
VL 30
IS 4
BP 1612042
EP 1612043
DI 10.3389/pore.2024.1612042
PG 2
ER
PT J
AU Jia, G
Li, X
AF Jia, Guohua
Li, Xiangpan
TI Survival trends of gastrointestinal stromal tumor in real-world settings: a population-based retrospective study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE GIST; survival; tumor-specific mortality; trend; outcome
ID GIST; survival; tumor-specific mortality; trend; outcome
AB Purpose: This study aims to evaluate whether survival outcomes for GIST patients have improved over the past decades and to identify the specific patient subgroups that have benefited from advances in treatment. Patients and methods: A total of 4,127 GIST patients diagnosed between January 1980, and December 2019, were included in this study using data from the Surveillance, Epidemiology, and End Results (SEER)-9 Registries. Survival differences among GIST patients were analyzed across five time periods (1980–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019) and within demographic, neoplastic, temporal, economic, and geographic categories using the log-rank test. Multivariable Cox regression models were employed to identify risk factors associated with GIST-specific survival. Associations between time periods and GIST-specific mortality (TSM) were examined using a multivariable Cox regression model. Results: Survival outcomes for GIST patients significantly improved in the 2000–2009 period but showed no substantial improvement in the 2010–2019 period. After adjusting for age, gender, tumor location, ethnicity, tumor stage, median household income, and geographic area, the multivariable Cox regression models revealed that older age (≥65 years) (HR = 1.977, 95% CI = 1.470–2.657), tumors located outside the gastrointestinal tract (HR = 1.505, 95% CI = 1.267–1.786), regional lesions (HR = 2.225, 95% CI = 1.828–2.708), and distant lesions (HR = 5.177, 95% CI = 4.417–6.069) were independent risk factors for TSM (p < 0.05). After adjusting for time periods and age, gender, tumor location, tumor stage, median household income, patients in 2000–2004 (HR = 0.662, 95% CI = 0.523–0.839), 2005–2009 (HR = 0.431, 95% CI = 0.339–0.549), 2010–2014 (HR = 0.437, 95% CI = 0.341–0.561), and 2015–2019 (HR = 0.365, 95% CI = 0.273–0.489) had a significantly lower risk of TSM than patients in 1980–1999 (p < 0.05). Similarly, patients in 2005–2009 (HR = 0.661, 95% CI = 0.555–0.788), 2010–2014 (HR = 0.696, 95% CI = 0.578–0.838), and 2015–2019 (HR = 0.607, 95% CI = 0.476–0.773) also had a significantly lower risk of TSM than patients in 2000–2004 (p < 0.05). However, patients in 2010–2014 (HR = 1.042, 5% CI = 0.863–1.258) and 2015–2019 (HR = 0.945, 95% CI = 0.734–1.216) did not have a significantly lower risk of TSM compared to patients in 2005–2009 (p > 0.05). Conclusion: GIST survival has significantly improved during the period 2000–2009 but showed no substantial improvement in 2010–2019, with the turning point for lower risk of TSM being 2005. Innovative strategies are needed to further improve survival outcomes for GIST patients, particularly for older patients and those with tumors originating outside the gastrointestinal tract.
C1 [Jia, Guohua] Wuhan University, Renmin Hospital, Cancer CenterWuhan, Hubei, China.
[Li, Xiangpan] Wuhan University, Renmin Hospital, Department of OncologyWuhan, Hubei, China.
RP Li, X (reprint author), Wuhan University, Renmin Hospital, Department of Oncology, Wuhan, China.
EM rm001227@whu.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611896
EP 1611906
DI 10.3389/pore.2025.1611896
PG 11
ER
PT J
AU Fellows, D
Kotowska, J
Stevenson, Th
Brown, J
Orosz, Zs
Siddiqi, A
Whitwell, D
Cosker, Th
GIbbons, Ch
AF Fellows, David
Kotowska, Julia
Stevenson, Thomas
Brown, Jennifer
Orosz, Zsolt
Siddiqi, Ather
Whitwell, Duncan
Cosker, Thomas
GIbbons, L. M. H. Christopher
TI Management and surveillance of metastatic giant cell tumour of bone
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE giant cell tumor of bone; pulmonary metastasis; sarcoma; orthopaedic oncology; surveillance
ID giant cell tumor of bone; pulmonary metastasis; sarcoma; orthopaedic oncology; surveillance
AB Giant cell tumour of bone (GCTB) is viewed as a benign, locally aggressive primary bone tumour with metastatic potential. Current management is surgery with bone curettage or resection and systemic therapy with denosumab. Diagnosis is confirmed histologically prior to surgery, with staging for pulmonary disease, as pulmonary metastases (PM) reportedly occur in <8%. This study aimed to assess incidence, surveillance and management of PM in patients with GCTB, with histopathological review. A retrospective audit of the Oxford bone tumour registry was performed from January 2014 – October 2023. Inclusion criterion was histological confirmation of GCTB. Exclusion criteria were incomplete medical, imaging or histology records, or referral for secondary MDT opinion for diagnosis. From an initial group of 126 GCTB patients, 83 patients met the full selection criteria. Pulmonary metastases were identified in 11 patients. Three with PM were excluded on histopathological review as being giant cell rich osteosarcoma rather than metastatic GCTB. This left 8 (9.6%) patients, one had PM at presentation and seven at follow-up between 2 and 42 months. Two were histologically confirmed after cardiothoracic surgery and biopsy, six radiologically diagnosed. Three (37.5%) patients with PM have died (between 1 and 12 months after confirmed PM), five are alive with stable disease. Seven (87.5%) of patients with pulmonary disease were treated with denosumab/chemotherapy (three before, four after pulmonary diagnosis). Five (62.5%) with pulmonary disease had recurrence of local disease requiring further surgery. Local recurrence was an independent risk factor for PM on statistical analysis. GCTB may present with PM, but more commonly, metastasis occurs after surgery, presenting on surveillance and can progress. There were no distinct differences in histopathological appearance between patients with GCTB that developed PM and those that did not, therefore morphological features of the tumour cannot be currently used to predict tumour behaviour. PM can behave aggressively, necessitating identifying histological markers to recognise patients at risk of metastatic GCTB, for example, through mRNA single cell analysis. We propose GCTB patients with PM receive regular chest surveillance with PET scan and/or CT to monitor disease progression, and a multi-centre audit of GCTB outcome undertaken to further define optimal clinical management.
C1 [Fellows, David] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[Kotowska, Julia] Hampshire Hospitals NHS Foundation Trust, Trauma and OrthopaedicsBasingstoke, UK.
[Stevenson, Thomas] Institute of Naval Medicine, Trauma and OrthopaedicsAlverstoke, UK.
[Brown, Jennifer] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[Orosz, Zsolt] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[Siddiqi, Ather] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[Whitwell, Duncan] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[Cosker, Thomas] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
[GIbbons, L. M. H. Christopher] Nuffield Orthopaedic Centre, Oxford Sarcoma ServiceOxford, England, UK.
RP Fellows, D (reprint author), Nuffield Orthopaedic Centre, Oxford Sarcoma Service, Oxford, UK.
EM david.fellows2@nhs.net
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611916
EP 1611926
DI 10.3389/pore.2025.1611916
PG 11
ER
PT J
AU Budi, L
Hammer, D
Varga, R
Muller, V
Tarnoki, DA
Tarnoki, LD
Meszaros, M
Bikov, A
Horvath, P
AF Budi, Lilla
Hammer, Daniel
Varga, Rita
Muller, Veronika
Tarnoki, Domonkos Adam
Tarnoki, Laszlo David
Meszaros, Martina
Bikov, Andras
Horvath, Peter
TI Anti-ceramide antibody and sphingosine-1-phosphate as potential biomarkers of unresectable non-small cell lung cancer
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE S1P; anti-ceramide antibody; NSCLC; biomarkers; lung cancer
ID S1P; anti-ceramide antibody; NSCLC; biomarkers; lung cancer
AB Objectives: Spingosine-1-phosphate (S1P) and ceramides are bioactive sphingolipids that influence cancer cell fate. Anti-ceramide antibodies might inhibit the effects of ceramide. The aim of this study was to assess the potential role of circulating S1P and anti-ceramide antibody as biomarkers in non-small cell lung cancer (NSCLC). Methods: We recruited 66 subjects (34 controls and 32 patients with NSCLC). Patient history and clinical variables were taken from all participants. Venous blood samples were collected to evaluate plasma biomarkers. If bronchoscopy was performed, bronchial washing fluid (BWF) was also analyzed. We measured the levels of S1P and anti-ceramide antibody with ELISA. Results: S1P levels were significantly higher in the NSCLC group (3770.99 ± 762.29 ng/mL vs. 366.53 ± 249.38 ng/mL, patients with NSCLC vs. controls, respectively, p < 0.001). Anti-ceramide antibody levels were significantly elevated in the NSCLC group (278.70 ± 19.26 ng/mL vs. 178.60 ± 18 ng/mL, patients with NSCLC vs. controls, respectively, p = 0.007). Age or BMI had no significant effect on anti-ceramide antibody or S1P levels. BWF samples had higher levels of anti-ceramide antibody (155.29 ± 27.58 ng/mL vs. 105.87 ± 9.99 ng/mL, patients with NSCLC vs. controls, respectively, p < 0.001). Overall survival (OS) was 13.36 months. OS was not affected by anti-ceramide antibody or S1P levels. Conclusion: Higher levels of S1P and anti-ceramide antibody were associated with active cancer. These results suggest that sphingolipid alterations might be important features of NSCLC.
C1 [Budi, Lilla] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Hammer, Daniel] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Varga, Rita] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Muller, Veronika] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Tarnoki, Domonkos Adam] Semmelweis University, Medical Imaging CenterBudapest, Hungary.
[Tarnoki, Laszlo David] Semmelweis University, Medical Imaging CenterBudapest, Hungary.
[Meszaros, Martina] Semmelweis University, Department of PulmonologyBudapest, Hungary.
[Bikov, Andras] Manchester Academic Health Science Centre, Manchester University National Health Service Foundation Trust, Wythenshawe HospitalManchester, UK.
[Horvath, Peter] Semmelweis University, Department of PulmonologyBudapest, Hungary.
RP Budi, L (reprint author), Semmelweis University, Department of Pulmonology, Budapest, Hungary.
EM budi.lilla@semmelweis.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611929
EP 1611938
DI 10.3389/pore.2024.1611929
PG 10
ER
PT J
AU Hou, Ch
Song, X
Chen, H
Chang, Ch
Lu, J
Li, Ch
Qu, H
Guo, R
Xu, J
Xu, L
AF Hou, Chunxiao
Song, Xueru
Chen, Hongwei
Chang, Chengdong
Lu, Jinfeng
Li, Cheng
Qu, Haiyan
Guo, Rui
Xu, Jingyi
Xu, Liming
TI A novel automated IHC staining system for quality control application in ALK immunohistochemistry testing
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE automated; quality control; anaplastic lymphoma kinase gene ALK; rabbit monoclonal antibody; controls in liquid form (CLFs); lung adenocarcinoma
ID automated; quality control; anaplastic lymphoma kinase gene ALK; rabbit monoclonal antibody; controls in liquid form (CLFs); lung adenocarcinoma
AB The establishment of positive and negative controls in immunohistochemistry (IHC) screening for anaplastic lymphoma kinase (ALK) rearrangements is essential in the treatment of lung adenocarcinoma. However, positive control of patient tissue is rare and comes with ethical issues. A novel automated solution for ALK IHC quality control management was investigated by comparison with the established D5F3 antibody on the VENTANA system in 87 lung adenocarcinoma specimens with known ALK status re-analyzed by fluorescence in situ hybridization. The BP6165 concentrated antibody on the LYNX480 PLUS platform demonstrated excellent sensitivity and specificity (98.30% and 100%, respectively) in 87 biopsy specimens. The ALK controls in liquid form (CLFs) applied in an automated way showed a more regular circular shape and better cell distribution than those applied manually. In addition, the novel controls can show changes in the same pattern as tissue controls under different antibody concentrations and antigen retrieval conditions. The automated solution for ALK IHC quality control management provides a convenient solution without the consumption of scarce tissue for IHC testing in day-to-day pathology practice. The availability of standardized protocols for the detection of ALK rearrangements using the BP6165 concentrated antibody on the LYNX480 PLUS platform will expand the number of laboratories that can reliably and consistently determine the eligibility of patients with lung adenocarcinoma for treatment with ALK tyrosine kinase inhibitors.
C1 [Hou, Chunxiao] Haining People’s Hospital, Department of PathologyHaining, Zhejiang, China.
[Song, Xueru] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, China.
[Chen, Hongwei] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, China.
[Chang, Chengdong] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, China.
[Lu, Jinfeng] Hangzhou Bailing Biotechnology Co., Ltd.Hangzhou, China.
[Li, Cheng] Hangzhou Bailing Biotechnology Co., Ltd.Hangzhou, China.
[Qu, Haiyan] Hangzhou Bailing Biotechnology Co., Ltd.Hangzhou, China.
[Guo, Rui] Hangzhou Bailing Biotechnology Co., Ltd.Hangzhou, China.
[Xu, Jingyi] Hangzhou Bailing Biotechnology Co., Ltd.Hangzhou, China.
[Xu, Liming] Zhejiang University School of Medicine, Affiliated Hangzhou First People’s Hospital, Department of Surgical PathologyHangzhou, China.
RP Hou, Ch (reprint author), Haining People’s Hospital, Department of Pathology, Haining, China.
EM 110080389@qq.com
CR Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, et al. Eml4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch, 2012, 461:245–57., DOI 10.1007/s00428-012-1281-4
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De Mello RA, Liu DJ, Aguiar PN, Tadokoro H. Egfr and Eml4-ALK updated therapies in non-small cell lung cancer. Recent Pat Anticancer Drug Discov, 2016, 11:393–400., DOI 10.2174/1574892811666160803090944
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Larkins E, Blumenthal GM, Chen H, He K, Agarwal R, Gieser G, et al. FDA approval: alectinib for the treatment ofmetastatic, ALK-positive non-small cell lung cancer following crizotinib. Clin Cancer Res, 2016, 22:5171–6., DOI 10.1158/1078- 0432.Ccr-16-1293
Conde E, Hernandez S, Prieto M, Martinez R, Lopez-Rios F. Profile of ventana ALK, D5f3, companion diagnostic assay for non-small-cell lung carcinomas. Expert Rev Mol Diagn, 2016, 16:707–13., DOI 10.1586/14737159.2016.1172963
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611964
EP 1611974
DI 10.3389/pore.2025.1611964
PG 11
ER
PT J
AU Almasi, Sz
Balajthy, Zs
Barath, B
Torok, KZs
Szaszak, P
Lantos, T
Kovari, B
Sejben, A
AF Almasi, Szintia
Balajthy, Zsofia
Barath, Bence
Torok, Krisztina Zsofia
Szaszak, Panna
Lantos, Tamas
Kovari, Bence
Sejben, Anita
TI Examination of non-conventional dysplasias adjacent to colorectal adenocarcinoma in patients with IBD
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE non-conventional dysplasia; colorectal adenocarcinoma; inflammatory bowel disease; ulcerative colitis; Crohn’s disease
ID non-conventional dysplasia; colorectal adenocarcinoma; inflammatory bowel disease; ulcerative colitis; Crohn’s disease
AB Objective: Recently, several non-conventional variants of IBD-associated dysplasia have been described; however, their prevalence in Central-Eastern Europe is unknown. We aimed to perform a retrospective pilot study by reevaluating several IBD-associated adenocarcinoma cases to survey the incidence of adjacent non-conventional dysplasia and validate that recent North American findings may apply to a European population. Methods: Retrospectively, 28 randomly chosen cases of IBD-associated adenocarcinomas diagnosed between 2010 and 2022 were re-evaluated. The patient’s sex, age (at the diagnosis of IBD and neoplasia), type of IBD, type of specimen [biopsy (n = 8)/surgical specimen (n = 20)], histological type, grade, localisation, stage, disease-free (DFS) and overall survival (OS) were obtained. Statistical analyses were carried out by using Mann-Whitney (continuous variables), Fisher’s exact (categorical variables), Kaplan-Meier (DFS/OS curves), and logrank test (survival curves). Results: Exclusively, conventional dysplasia was observed in 11, and nonconventional dysplasia in 8 patients. Combined conventional and nonconventional dysplasia was detected in 9 patients. Non-conventional dysplasia showing a combination of multiple subtypes was noted in 10 cases. Altogether, 25 non-conventional dysplastic foci were identified, which were diagnosed as hypermucinous (n = 9), goblet cell-deficient (n = 6), serrated not otherwise specified (NOS) (n = 6), and traditional serrated adenoma-like (n = 4). The majority of non-conventional dysplasias were associated with ulcerative colitis (n = 12). Mucinous adenocarcinoma was exclusively associated with non-conventional dysplasia, while medullary carcinoma was only with conventional dysplasias (p = 0.014 and 0.041). Conclusion: Based on our results, non-conventional dysplasia is common (60%) adjacent to IBD-associated adenocarcinomas in a Central-Eastern European population and may be detected in biopsies. As multiple recent publications reported evidence of a worse prognosis and more common flat morphology compared to conventional dysplasias, their recognition is of great importance, and stricter follow-up with random biopsy samples may be considered.
C1 [Almasi, Szintia] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Balajthy, Zsofia] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Barath, Bence] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Torok, Krisztina Zsofia] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Szaszak, Panna] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Lantos, Tamas] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
[Kovari, Bence] Harvard Medical School, Mass General BrighamBoston, MA, USA.
[Sejben, Anita] University of Szeged, Albert Szent-Gyorgyi Medical SchoolSzeged, Hungary.
RP Sejben, A (reprint author), University of Szeged, Albert Szent-Gyorgyi Medical School, Szeged, Hungary.
EM sejben.anita@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611978
EP 1611989
DI 10.3389/pore.2024.1611978
PG 12
ER
PT J
AU Francis, SS
Sharma, S
AF Francis, Sebastian Sachin
Sharma, Swati
TI Tumour budding in invasive ductal breast carcinomas: correlation with clinicopathological prognostic parameters and hormone receptor status
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE invasive breast carcinoma; intra tumoral budding; peripheral tumour budding; prognostic parameters; Ki-67
ID invasive breast carcinoma; intra tumoral budding; peripheral tumour budding; prognostic parameters; Ki-67
AB Introduction: Breast cancer is a leading cause of morbidity and mortality among women. Advances in molecular biology have improved detection and treatment, but conventional histopathological factors remain crucial for prognosis. Tumour budding, defined as clusters of less than 5 tumour cells detached from the main tumour, has been linked to poor prognosis in several cancers. This study explores the association between intra-tumoral budding (ITB) and peripheral tumour budding (PTB) with known prognostic factors in Invasive Breast Carcinoma of no special type (IBC NST). Materials and methods: This retrospective study analysed 70 cases of IBC NST diagnosed at Kasturba Medical College, Manipal, between January 2020 and December 2021. Tumour budding was classified as high-grade or low-grade based on density, which denotes the number of buds per x20 field. Clinicopathological data, including hormone receptor status, Ki-67 index, lymphovascular invasion (LVI), perineural invasion (PNI), and axillary lymph node involvement, were obtained. Statistical analyses were performed to identify a significant association between tumour budding and these factors. Univariate and multivariate logistic regression analyses were also done to demonstrate the significance of association. Results: High-grade PTB showed significant associations with LVI (p = 0.046), PNI (p = 0.017), and axillary lymph node involvement (p = 0.021). In contrast, high-grade ITB was only significantly correlated with axillary lymph node involvement (p = 0.044). LVI (p-value = 0.240) and axillary lymph node involvement (p-value = 0.142) did not show any association with PTB on multivariate analysis and PNI (p-value = 0.074) near significant association with PTB). A significant inverse association was observed between PTB and Ki-67 (p = 0.012), which remained significant in univariate and multivariate analysis (p-value = 0.017). No significant associations were found between tumour budding and hormone receptor status or menopausal status. Conclusion: Peripheral tumour budding (PTB) is significantly associated with several poor prognostic factors in IBC NST, while intra-tumoral budding (ITB) correlates primarily with axillary lymph node involvement. Tumor budding, particularly PTB, could serve as an important prognostic marker in breast cancer. Further research is needed to standardize tumour budding assessment in clinical practice.
C1 [Francis, Sebastian Sachin] Manipal Academy of Higher Education, Kasturba Medical College, Center of Basic Sciences, Department of PathologyManipal, Karnataka, India.
[Sharma, Swati] Manipal Academy of Higher Education, Kasturba Medical College, Center of Basic Sciences, Department of PathologyManipal, Karnataka, India.
RP Sharma, S (reprint author), Manipal Academy of Higher Education, Kasturba Medical College, Center of Basic Sciences, Department of Pathology, Manipal, India.
EM swati.sharma@manipal.edu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611983
EP 1611992
DI 10.3389/pore.2025.1611983
PG 10
ER
PT J
AU Qiu, Z
Wu, J
Pang, G
Xu, X
Lin, J
Wang, P
AF Qiu, Zijian
Wu, Jiaji
Pang, Guanchao
Xu, Xia
Lin, Jun
Wang, Pingli
TI CD34 evaluation of microvasculature in lung adenocarcinoma and its microvascular density predicts postoperative tumor recurrence
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE CD34; microvascular density; lung adenocarcinoma; prognosis; tumor recurrence
ID CD34; microvascular density; lung adenocarcinoma; prognosis; tumor recurrence
AB Background: Angiogenesis is closely associated with tumor growth and metastasis, and microvascular density (MVD) is currently the clinical standard for evaluating tumor angiogenesis. Thus, the detection of intratumoral MVD is of great significance for understanding disease progression and predicting patient prognosis. Methods: Tumor tissue sections of 238 patients with lung adenocarcinoma (LUAD) who underwent radical surgery were retrospectively analyzed. Immunohistochemical (IHC) staining was carried out using a CD34 polyclonal antibody to determine intratumoral MVD, and the relationship of CD34-MVD with the clinicopathological characteristics and survival time of LUAD patients was analyzed. Results: CD34-MVD was associated with tumor size, lymph node metastasis, tumor recurrence, and patient survival status; patients with tumor size ≤3 cm (P = 0.015), negative for lymph node metastasis (P = 0.049), no tumor recurrence (P = 0.021), and survival (P = 0.042) had higher MVD. Survival analysis suggested that patients with high MVD had higher disease-free survival (log-rank P = 0.005) and overall survival (log-rank P = 0.004) compared to patients with low MVD. The Cox proportional hazards model showed that a high MVD (P = 0.022) reduced the risk of postoperative tumor recurrence in patients with LUAD. Conclusion: Decreased intratumoral CD34 positive microvessels were associated with tumor development in patients with LUAD. CD34-MVD is an independent risk factor affecting postoperative tumor recurrence in patients with LUAD and can be used as a prognostic indicator for this group of patients.
C1 [Qiu, Zijian] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of Radiation OncologyQuzhou, Zhejiang, China.
[Wu, Jiaji] The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Department of Respiratory MedicineYiwu, Zhejiang, China.
[Pang, Guanchao] The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Respiratory and Critical Care MedicineHangzhou, Zhejiang, China.
[Xu, Xia] The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of PathologyHangzhou, Zhejiang, China.
[Lin, Jun] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of PathologyQuzhou, Zhejiang, China.
[Wang, Pingli] The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Respiratory and Critical Care MedicineHangzhou, Zhejiang, China.
RP Wang, P (reprint author), The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Respiratory and Critical Care Medicine, Hangzhou, China.
EM pingliwang@zju.edu.cn
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611985
EP 1611994
DI 10.3389/pore.2025.1611985
PG 10
ER
PT J
AU Schwab, H
Kerkhoff, M
Plaumann, P
Collaud, S
Dirksen, U
Theegarten, D
Herold, Th
Kalbourtzis, S
Bolukbas, S
Hegedus, B
Hegedus, L
AF Schwab, Hannah
Kerkhoff, Maximilian
Plaumann, Pauline
Collaud, Stephane
Dirksen, Uta
Theegarten, Dirk
Herold, Thomas
Kalbourtzis, Stavros
Bolukbas, Servet
Hegedus, Balazs
Hegedus, Luca
TI Characterization of a novel sarcoma cell line with an EWSR1:: POU2AF3 fusion
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE sarcoma; chemotherapy; EWSR1; POU2AF3; patient derived cell line
ID sarcoma; chemotherapy; EWSR1; POU2AF3; patient derived cell line
AB Sarcomas with an EWSR1::POU2AF3(COLCA2) fusion are a very recently described entity of preferentially sinonasal origin and with undifferentiated round/spindle cell morphology. We established a novel cell line (PF1095) carrying a EWSR1::POU2AF3 fusion from the malignant pleural effusion of a 25-year-old sarcoma patient. The patient was first diagnosed with poorly differentiated neuroendocrine carcinoma based on tumor cell morphology and positivity to markers such as EMA, synaptophysin, and CD56. Later, the EWSR1 translocation was identified in the tumor cells with unknown partners and the patient received chemotherapy according to the Ewing 2008 protocol in combination with surgery and proton beam radiotherapy. At the time of cell line establishment, the disease progressed to pleural sarcomatosis with pleural effusion. In the cell line, we identified POU2AF3 as a fusion partner of EWSR1 and a TP53 frameshift deletion. Next, we determined the sensitivity of PF1095 cells to the currently approved chemotherapies in comparison to two conventional Ewing sarcoma lines (EW-7 and MHH-ES1) with the two most frequent EWSR::FLI1 fusions. Finally, we tested potential new combination therapies. We performed cell viability, proliferation, and cell cycle assays. We found that the proliferation rate of PF1095 cells was much slower than the EWSR1::FLI1 fusion lines and they also had a lower sensitivity to both irinotecan and doxorubicin treatment. Expression level of SLFN11, a predictor of sensitivity to DNA damaging agents, was also lower in PF1095 cells. Combination treatment with the PARP inhibitors olaparib and irinotecan or doxorubicin synergistically reduced cell viability and induced cell death and cell cycle arrest. This unique cell model provides an opportunity to test therapeutic approaches preclinically for this novel and aggressive sarcoma entity.
C1 [Schwab, Hannah] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Kerkhoff, Maximilian] University Medicine Essen, West German Cancer Center, Pediatrics IIIEssen, Germany.
[Plaumann, Pauline] University Medicine Essen, West German Cancer Center, Pediatrics IIIEssen, Germany.
[Collaud, Stephane] University of Witten/Herdecke, Cologne Merheim Hospital, Department of Thoracic SurgeryCologne, Germany.
[Dirksen, Uta] University Medicine Essen, West German Cancer Center, Pediatrics IIIEssen, Germany.
[Theegarten, Dirk] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Herold, Thomas] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Kalbourtzis, Stavros] University of Duisburg-Essen, University Hospital of Essen, Institute of PathologyEssen, Germany.
[Bolukbas, Servet] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Balazs] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
[Hegedus, Luca] University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic SurgeryEssen, Germany.
RP Hegedus, B (reprint author), University Duisburg-Essen, University Medicine Essen–Ruhrlandklinik, Department of Thoracic Surgery, Essen, Germany.
EM balazs.hegedues@rlk.uk-essen.de
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611986
EP 1611997
DI 10.3389/pore.2025.1611986
PG 12
ER
PT J
AU Lippai, Z
Papp, G
Sapi, J
Dezso, K
Sapi, Z
AF Lippai, Zoltan
Papp, Gergo
Sapi, Johanna
Dezso, Katalin
Sapi, Zoltan
TI NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE soft tissue sarcoma; dedifferentiated liposarcoma; gene rearrangement; gene amplification; NTRK
ID soft tissue sarcoma; dedifferentiated liposarcoma; gene rearrangement; gene amplification; NTRK
AB The neurotrophic tyrosine kinase receptor (NTRK) gene family is of rising importance as their fusions are oncogenic, and specific target drugs are available to inhibit the chimera proteins. Pan-TRK antibody, which shows the overexpression of the NTRK1-2-3 genes, is a useful tool to detect tumors with or without NTRK gene alterations, due to high negative predictive value. Though it is well known that pan-TRK immunopositivity is usually not connected to NTRK fusion, the role of other possible genetic alterations is under-researched. In our previous work, we found 3 NTRK1 amplified cases out of 6 cases with recurrent NTRK1 tyrosine kinase domain mutation pair, so we extended our investigation to a larger series to estimate amplification frequency. Pan-TRK immunopositivity was seen in 76 of the 132 dedifferentiated liposarcomas cases, followed by NTRK1-2-3 break-apart FISH tests in 76 pan-TRK positive cases to detect oncogenic fusions or other copy number alterations of these genes. None of the pan-TRK immunopositive dedifferentiated liposarcomas showed absolutely certain sign of fusion, however, 18 (28%) cases showed amplification of one of the genes, 13 had polysomy, 34 were normal, 11 were not evaluable. The extent of pan-TRK immunoreaction showed a positive correlation (p = 0.002) with the NTRK status found by FISH. Analyzing publicly available data from large series of 265 liposarcoma samples consisting of both welldifferentiated and dedifferentiated liposarcoma case, 23 (8.6%) cases showed a mutual exclusive amplification of the NTRK genomic loci in a nonpreselected, independent patient population indicating that our findings are presented in other cohorts. Our results underline the so far not revealed frequent occurrence of NTRK amplifications which might be important in the TRK inhibition therapy.
C1 [Lippai, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Papp, Gergo] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Johanna] Obuda University, Physiological Controls Research Center, John von Neumann Faculty of InformaticsBudapest, Hungary.
[Dezso, Katalin] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Sapi, Zoltan] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
RP Sapi, Z (reprint author), Semmelweis University, 1st Department of Pathology and Experimental Cancer Research, Budapest, Hungary.
EM sapi.zoltan.dr@gmail.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1611993
EP 1612001
DI 10.3389/pore.2024.1611993
PG 9
ER
PT J
TI Evaluating the correlation between pretreatment 18F-FDG PET/CT metabolic parameters and tumor-infiltrating lymphocyte levels in nonluminal breast cancer and impact on survival
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE tumor-infiltrating lymphocytes; nonluminal breast cancer; tumor heterogeneity indices; FDG; metabolic parameter
ID tumor-infiltrating lymphocytes; nonluminal breast cancer; tumor heterogeneity indices; FDG; metabolic parameter
AB Background and Objectives: This study aims to evaluate the correlation between Tumor-Infiltrating Lymphocyte (TIL) levels and Fluorine-18 fluorodeoxyglucose (18F-FDG) metabolic parameters, including spleen and bone marrow FDG uptake and tumor heterogeneity in non-luminal breast cancers (NLBC), and to elucidate their association with survival outcomes. Methods: We retrospectively analyzed data from 100 females with stage 2–4 NLBC who underwent pretreatment 18F-FDG Positron emission tomography-computed tomography (PET/CT). TIL was scored based on Hematoxylin-Eosin-stained specimens and 18F-FDG PET metabolic parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), liver, spleen, and bone marrow FDG uptake were calculated. Heterogeneity Index (HI)1, HI2, and HI3 indices were analyzed with FDG metabolic parameters. The association between these factors and overall survival was analyzed using multivariate Cox regression models. Results: TIL showed weak negative correlations with tumor size, tumor (T), and metastasis (M) stages. No significant correlation was found between TIL levels and overall SUV values. However, in stage 4, TIL correlated positively with liver, spleen, and bone marrow SUV values and negatively with heterogeneity indices (HI2, HI3). Higher tumor size, HI values, and Bone marrow-to-liver ratio (BLR) SUVmean were associated with increased mortality. A TIL cut-off value of <5 was linked to significantly worse survival. Conclusion: Our study demonstrates a strong connection between TIL, FDG metabolic parameters, and tumor heterogeneity, particularly in advanced NLBC. Although TIL is not generally associated with SUV values, its association with certain metabolic and heterogeneity indices suggests that it is important in influencing survival. Further research involving larger cohorts and diverse breast cancer subtypes is needed to validate these results.
CR Denkert C, Minckwitz G, Darb-Esfahani S, Lederer B, Heppner B, Weber K, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol, 2018, 19:40–50., DOI 10.1016/S1470-2045(17)30904-X
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de Moraes FCA, Souza MEC, Sano VKT, Moraes RA, Melo AC. Association of tumor-infiltrating lymphocytes with clinical outcomes in patients with triplenegative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta-analysis. Clin Transl Oncol, 2024))., DOI 10.1007/s12094-024-03661-8
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612014
EP 1612027
DI 10.3389/pore.2024.1612014
PG 14
ER
PT J
AU Zecevic, A
Blanka-Protic, A
Jandric, A
Adzic-Vukicevic, T
AF Zecevic, Andrej
Blanka-Protic, Ana
Jandric, Aleksandar
Adzic-Vukicevic, Tatjana
TI Are patients with chronic obstructive pulmonary disease at a greater risk for the development of autoimmune thyroiditis as an adverse event of immunotherapy in non-small cell lung cancer treatment?
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE chronic obstructive lung disease; non-small cell lung cancer; immunotherapy; thyroiditis; adverse event
ID chronic obstructive lung disease; non-small cell lung cancer; immunotherapy; thyroiditis; adverse event
AB Introduction: Immunotherapy has made a significant improvement in the treatment of patients with non-small cell lung cancer (NSCLC). It has a role in boosting the immune system, so it can fight cancer cells. Sometimes, this mechanism can lead to an overstimulation or misdirection of immune response, so it can act against the body itself. One of the organs most affected by this reaction is the thyroid gland, and there is no definitive explanation of the causes of this adverse event. Material and methods: In this retrospective observational study, we enrolled 103 patients with NSCLC and high PD-L1 expression (>= 50%) who were treated in our Clinic for pulmonology, University Clinical Center of Serbia, using Pembrolizumab as the first-line therapy. Results: Data analysis showed that 41 (39.81%) of 103 patients in our study had an adverse event of immunotherapy, and 21 of them had autoimmune thyroiditis (20.39%). Of all the patients, 19 of them were treated for chronic obstructive pulmonary disease (COPD) before the onset of Pembrolizumab. During treatment, eight of these patients developed thyroid dysfunction. Patients with COPD were at increased risk of developing autoimmune thyroiditis compared to non-COPD patients (OR 3.9 95% CI 1.135–13.260, p = 0.0227). Conclusion: Our study showed that patients dealing with COPD have a 3.9 times greater risk of developing autoimmune thyroiditis as an adverse event during Pembrolizumab treatment compared with patients without COPD.
C1 [Zecevic, Andrej] University Clinical Center of Serbia, Clinic for PulmonologyBelgrade, Serbia.
[Blanka-Protic, Ana] University Clinical Center of Serbia, Clinic for PulmonologyBelgrade, Serbia.
[Jandric, Aleksandar] University Clinical Center of Serbia, Clinic for PulmonologyBelgrade, Serbia.
[Adzic-Vukicevic, Tatjana] University Clinical Center of Serbia, Clinic for PulmonologyBelgrade, Serbia.
RP Zecevic, A (reprint author), University Clinical Center of Serbia, Clinic for Pulmonology, Belgrade, Serbia.
EM zecevic92andrej@gmail.com
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Cavic M, Kovacevic T, Zaric B, Stojiljkovic D, Korda NJ, Rancic M, et al. Lung cancer in Serbia. J Thorac Oncol, 2022, 17(7):867–72., DOI 10.1016/j.jtho.2022. 04.010
Li Z, Xia Y, Xia M, Liu C, Wang T, Liu Y, et al. Immune-related thyroid dysfunction is associated with improved long-term prognosis in patients with nonsmall cell lung cancer treated with immunotherapy: a systematic review and metaanalysis. J Thorac Dis, 2023, 15(2):690–700., DOI 10.21037/jtd-23-254
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612022
EP 1612026
DI 10.3389/pore.2025.1612022
PG 5
ER
PT J
AU Nagy, FZs
Pfliegler, Gy
Kosa, J
Arvai, K
Istenes, I
Doros, A
Timar, B
Lakatos, P
Demeter, J
AF Nagy, Flora Zsofia
Pfliegler, Gyorgy
Kosa, Janos
Arvai, Kristof
Istenes, Ildiko
Doros, Attila
Timar, Botond
Lakatos, Peter
Demeter, Judit
TI Case Report: Importance of high-throughput genetic investigations in the differential diagnosis of unexplained erythrocytosis
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE polyglobulia; WES; diagnostic; chuvash polycythaemia; pyruvate kinase hyperactivity
ID polyglobulia; WES; diagnostic; chuvash polycythaemia; pyruvate kinase hyperactivity
AB Introduction: Polycythemia indicates the pathological increase in the number of red blood cells and the rise of hematocrit values. Polyglobulia can be of primary or secondary origin, with the most common primary polycythemia being a myeloproliferative neoplasm, polycythemia vera. Polyglobulia patients may develop cardiovascular complications and thromboembolic events. The gold standard of first-line treatment in polycythemia vera is phlebotomy, which is indicated to keep the hematocrit value below 0.45. Until now the goal to be achieved in secondary polyglobulia has been similar. In secondary polyglobulia this rule of thumb needs to be re-evaluated as shown by the example of two patients suffering from different rare, genetically determined polyglobulias. In our article we present the case of these two patients and discuss the diagnostic and therapeutic principles to be applied in patients with rare, genetically determined polyglobulias. Patients and methods: After completing the usual diagnostic algorithm for polyglobulia no cause could be identified in two of our male patients. Therefore, we set out to perform whole exome sequencing in both patients. Our analysis did not include copy number analysis. Results: In Patient 1 the p.Ser179Pro variant in the VHL gene was detected in the homozygous state, which is classified as likely pathogenic according to the ACMG guidelines. Homozygous VHL mutations are implicated in Chuvash polycythemia. Segregation analysis was declined by the family. In Patient 2 the PKLR gene p.His306Gln variant was detected in the heterozygous form. The gene plays a role in pyruvate metabolism. Family screening did not detect this variant in healthy family members. Discussion: We identified rare, possibly pathogenic genetic variants in two patients with polyglobulia and as a consequence of the genetic diagnosis we implemented individualized patient monitoring. We recommend the utilization of high-throughput genomic testing in cases with unexplained polyglobulia.
C1 [Nagy, Flora Zsofia] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Pfliegler, Gyorgy] Debreceni Egyetem Klinikai Kozpont, Ritka Betegsegek Szakertoi Kozpont es Belgyogyaszati IntezetDebrecen, Hungary.
[Kosa, Janos] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Arvai, Kristof] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Istenes, Ildiko] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Doros, Attila] Semmelweis University, Department of Radiology and OncotherapyBudapest, Hungary.
[Timar, Botond] Semmelweis University, 1st Department of Pathology and Experimental Cancer ResearchBudapest, Hungary.
[Lakatos, Peter] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
[Demeter, Judit] Semmelweis University, Department of Internal Medicine and OncologyBudapest, Hungary.
RP Nagy, FZs (reprint author), Semmelweis University, Department of Internal Medicine and Oncology, Budapest, Hungary.
EM nagy.zsofia.flora@semmelweis.hu
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612037
EP 1612043
DI 10.3389/pore.2025.1612037
PG 7
ER
PT J
AU Qiu, Z
Ke, F
Zhu, X
AF Qiu, Zijian
Ke, Fei
Zhu, Xiaoping
TI Case report: Alectinib-associated intestinal ulceration and colitis in a patient with non-small cell lung cancer and effective treatment with Mesalazine
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Case Reports
DE Alectinib; intestinal ulcer; colitis; anaplastic lymphoma kinase inhibitor; non-small cell lung cancer
ID Alectinib; intestinal ulcer; colitis; anaplastic lymphoma kinase inhibitor; non-small cell lung cancer
AB Background: Alectinib is effective in extending the survival of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) and generally has manageable side effects. However, intestinal ulcers and colitis are rare but serious adverse reactions linked to Alectinib, meriting further investigation into their causes. Case presentation: We report the case of a 62-year-old woman with NSCLC and brain metastases, who tested positive for ALK. She had been treated with Alectinib for nearly 4 years. The patient experienced diarrhea for 4 days, and a subsequent colonoscopy revealed pancolitis along with multiple ulcers in the terminal ileum and ileocecal valve. Given the severity of these symptoms, classified as a grade 3 adverse event by the Common Terminology Criteria for Adverse Events (CTCAE), Alectinib was discontinued. Treatment with oral enteric-coated Mesalazine tablets led to a resolution of the diarrhea and a significant improvement in the pancolitis and ulcers upon follow-up. The patient’s anticancer therapy was subsequently switched to Ceritinib capsules. At follow-up, she demonstrated a stable tumor condition with no recurrence of intestinal ulcers or colitis. Conclusion: To our knowledge, this is the first reported case of intestinal ulceration and colitis induced by Alectinib. Although such adverse events are exceedingly rare, they require vigilant monitoring in clinical practice. Decisions on continuing with Alectinib should consider the severity of side effects, classified by CTCAE grade. For managing these specific adverse events, oral Mesalazine enteric-coated tablets appear to be an effective treatment option.
C1 [Qiu, Zijian] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of Radiation OncologyQuzhou, Zhejiang, China.
[Ke, Fei] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of PathologyQuzhou, Zhejiang, China.
[Zhu, Xiaoping] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of Radiation OncologyQuzhou, Zhejiang, China.
RP Zhu, X (reprint author), The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Department of Radiation Oncology, Quzhou, China.
EM 25229661@qq.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612040
EP 1612045
DI 10.3389/pore.2025.1612040
PG 6
ER
PT J
AU Csepregi, BA
Papp, E
Adamik, I
Csernak, E
Engi, H
Kuronya, Zs
Soos, E
Melegh, Zs
Toth, E
AF Csepregi, Beata Anna
Papp, Eszter
Adamik, Imola
Csernak, Erzsebet
Engi, Helga
Kuronya, Zsofia
Soos, Edina
Melegh, Zsombor
Toth, Erika
TI Impact of comprehensive genomic profiling on the diagnosis and clinical management of malignant mesenchymal tumours
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE next generation sequencing; comprehensive genomic profiling; targeted therapy; sarcoma; mesenchymal tumours
ID next generation sequencing; comprehensive genomic profiling; targeted therapy; sarcoma; mesenchymal tumours
AB Comprehensive genomic profiling (CGP) is becoming an increasingly important tool in the clinical management of different tumours, but there is still very limited data available on its usefulness from a therapeutic point of view in mesenchymal tumours. Between January 2022 and September 2024, we performed CGP analysis with means of Oncomine Comprehensive Assay Plus (OCAplus) on 94 malignant mesenchymal tumours. The analysis covered more than 500 unique genes for single-gene and multigene biomarker insights, including tumour mutational burden (TMB) and homologous recombination deficiency (HRD). Genomic DNA and total RNA were extracted from formalin-fixed paraffin-embedded tissue blocks. Twentyfour out of 94 patients (25.5%) had potentially actionable alterations: 17 (18%) had specific genetic alterations suitable for targeted therapies, 4 (4.2%) had a high TMB (>10 mut/Mb), and 5 (5.3%) had a high HRD score >15). One additional patient had BRCA1 mutation, but the HRD score was low. Three patients received targeted therapy: one patient with a CDK4-amplified tumour (dedifferentiated liposarcoma) received CDK4 inhibitor therapy, two patients with angiosarcoma showing high TMB received immune checkpoint inhibitor therapy, and one patient with a uterine leiomyosarcoma and high HRD score received PARP inhibitor therapy. In addition, two patients with malignant phyllodes tumours received multi-thyrosine kinase inhibitor therapy. In three cases, there was refinement or reassignment of the diagnosis, based on the CGP findings. Our results demonstrate that CGP can provide useful additional information and can be beneficial in the clinical management of patients with mesenchymal tumours.
C1 [Csepregi, Beata Anna] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Papp, Eszter] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Adamik, Imola] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Csernak, Erzsebet] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Engi, Helga] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Kuronya, Zsofia] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology DepartmentBudapest, Hungary.
[Soos, Edina] National Institute of Oncology, Urogenital Tumors and Clinical Pharmacology DepartmentBudapest, Hungary.
[Melegh, Zsombor] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
[Toth, Erika] National Institute of Oncology, Center of Surgical and Molecular Tumor PathologyBudapest, Hungary.
RP Toth, E (reprint author), National Institute of Oncology, Center of Surgical and Molecular Tumor Pathology, Budapest, Hungary.
EM dr.toth.erika@oncol.hu
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Ravi V, Subramaniam A, Zheng J, Amini B, Trinh VA, Joseph J, et al. Clinical activity of checkpoint inhibitors in angiosarcoma: a retrospective cohort study. Cancer, 2022, 128(18):3383–91., DOI 10.1002/cncr.34370
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Schipper LJ, Monkhorst K, Samsom KG, Bosch LJW, Snaebjornsson P, van Boven H, et al. Clinical impact of prospective whole genome sequencing in sarcoma patients. Cancers, Basel,, 2022, 14(2):436. PMID: 35053600; PMCID: PMC8773512., DOI 10.3390/cancers14020436
NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612065
EP 1612071
DI 10.3389/pore.2025.1612065
PG 7
ER
PT J
AU Talor, E
Timar, J
Lavin, P
Cipriano, J
Markovic, D
Ladanyi, A
Bondarenko, I
Stosic, S
Sobat, H
Zhukavets, A
Imamovic, N
Bankowska-Wozniak, M
Kisely, M
Jovic, R
Young, EMJ
AF Talor, Eyal
Timar, Jozsef
Lavin, Philip
Cipriano, John
Markovic, Dusan
Ladanyi, Andrea
Bondarenko, Igor
Stosic, Srboljub
Sobat, Hrvoje
Zhukavets, Aliaksandr
Imamovic, Nazim
Bankowska-Wozniak, Magdalena
Kisely, Mihaly
Jovic, Rajko
Young, Edward Massey James
TI Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma –the IT-MATTERS study
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Journal Article
DE Leukocyte interleukin injection (LI); immunotherapy; neoadjuvant; SCCHN; locally advanced disease; low-risk for recurrence; lower disease burden
ID Leukocyte interleukin injection (LI); immunotherapy; neoadjuvant; SCCHN; locally advanced disease; low-risk for recurrence; lower disease burden
AB The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naive resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400 IU (as interleukin-2 equivalent; 200 IU peritumorally, 200 IU perilymphatically) sequentially, daily 5 days/week for 3 weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Presurgery objective early response (45 objective early responders; 5 complete responses [CRs], 40 partial responses [PRs], confirmed by pathology at surgery. LI (+/− CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152–0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077–0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48–0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60 months, with 46.5 months median OS advantage (101.7 months vs. 55.2 months), respectively. Quality of life benefit for complete responders sustained for >3 years post LI treatment. Percent treatmentemergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.
C1 [Talor, Eyal] CEL-SCI CorporationVienna, VA, USA.
[Timar, Jozsef] Semmelweis University, 2nd Department of PathologyBudapest, Hungary.
[Lavin, Philip] Boston Biostatistics Research FoundationFramingham, MA, USA.
[Cipriano, John] CEL-SCI CorporationVienna, VA, USA.
[Markovic, Dusan] Ergomed GroupGuildford, UK.
[Ladanyi, Andrea] Orszagos Onkologiai Intezet, Nemzeti Tumorbiologiai LaboratoriumBudapest, Hungary.
[Bondarenko, Igor] State Institution “Dnipropetrovsk Medical Academy Under theMinistry of Health of Ukraine”, Oncology and Medical Radiology, Municipal Non-Commercial Enterprise “City Clinical Hospital No. 4” of Dnipro City Council, Head and Neck Pathology DepartmentDnipro, Ukraine.
[Stosic, Srboljub] Military Medical Academy, Clinic for Maxillofacial SurgeryBelgrade, Serbia.
[Sobat, Hrvoje] University Hospital for Tumors, University Clinical Hospital Center “Sestre Milosrdnice”Zagreb, Croatia.
[Zhukavets, Aliaksandr] N.N.Alexandrov National Cancer Centre of Belarus, Department of SurgeryMinsk, Belarus.
[Imamovic, Nazim] University Clinical Center Tuzla, Clinic for Plastic and Maxillofacial SurgeryTuzla, Bosnia and Herzegovina.
[Bankowska-Wozniak, Magdalena] Centrum Onkologii im Prof. F. Lukaszcsyka, Bydgoszcz, Department of SurgeryBydgoszcz, Poland.
[Kisely, Mihaly] Markusovszky Egyetemi Oktatokorhaz, Altalanos Sebeszeti OsztalySzombathely, Hungary.
[Jovic, Rajko] University Clinical Centre of Vojvodina, Clinic for Otorhinolaryngology and Head and Neck Surgery, Department of Laryngology, Oncology and PhoniatricsNovi Sad, Serbia.
[Young, Edward Massey James] McMaster University, St Joseph Healthcare HamiltonHamilton, ON, Canada.
RP Talor, E (reprint author), CEL-SCI Corporation, Vienna, USA.
EM etalor@cel-sci.com
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NR 1
PU Arányi Lajos Foundation
PI Budapest
PA Ulloi ut 26., Budapest H-1085, Hungary
SN 1219-4956
J9 PAOR
JI Pathol Oncol Res
PD JAN
PY 2025
VL 31
IS 1
BP 1612084
EP 1612100
DI 10.3389/pore.2025.1612084
PG 17
ER
EF